PMID- 7560358
TI  - Paget's disease.

PMID- 7560359
TI  - Histopathology of non-scarring alopecia.

PMID- 7560360
TI  - Remembrance and reminiscence.

PMID- 7560361
TI  - Violence and the health professional.

PMID- 7560362
TI  - Premature loss of the maxillary primary incisors: effect on speech production.
AB  - The residual effect of premature loss due to extraction of the four maxillary
      primary incisors on speech production was studied. The articulation of twenty-six
      subjects who had their teeth extracted before the age of five years was evaluated
      at eight, nine, or ten years old and compared with the articulation of an age
      matched comparison group with normal exfoliation of their incisors. T-tests for
      related measures revealed no statistically significant differences between the
      group with premature loss and the comparison group. These results suggest that
      loss of maxillary incisors in children younger than five years is not likely to
      result in defective articulation while the teeth are missing or when the
      permanent dentition is acquired.

PMID- 7560363
TI  - Effect of chewing gums on plaque pH after a sucrose challenge.
AB  - The objective of this study was to determine whether sugarless chewing gums
      sweetened with different sweeteners differ in their ability to reduce an
      acidogenic response from a 10 percent sucrose-rinse challenge. Five commercially
      available chewing gums and two control regimens ("no gum" or paraffin) were
      tested using a plaque pH telemetry system. The gums were sweetened with sucrose,
      high-intensity sweeteners (aspartame, saccharin, or acesulfame-K), or a polyol
      (xylitol). Using a seven-period randomized block design, eight adult panelists
      were challenged with a 10 percent sucrose solution and then randomly used one of
      the test regimens during each of the seven test sessions. Each two-hour test
      session was divided into five periods: resting baseline (five minutes); sucrose
      rinse challenge (two minutes); postsucrose challenge (ten minutes); gum chewing
      (ten minutes); post gum chewing (ninety-three minutes). The factors analyzed
      were: the area of the curve (pH X Time) below pH 5.5, the minimum plaque pH
      attained, the changes in plaque pH over relevant intervals, and the length of
      time the plaque pH remained below pH 5.5. The various response variables showed a
      similar pattern of statistically significant differences. All of the sugarless
      gums were effective in significantly increasing plaque pH and in reducing the
      area under the curve after the sucrose challenge compared with "no gum"
      treatment. No statistically significant differences were noted among the
      sugarless gums. The response to sucrose gum was intermediate between sugarless
      gums and "no gum" but was not statistically different from "no gum" or three of
      the sugarless gums.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560364
TI  - The effect of caries scoring systems on the association between dental caries and
      Streptococcus mutans.
AB  - The purpose of this study was to examine the effect of caries scoring systems on
      the association between caries indices and salivary counts of S. mutans in a
      group of ninety-eight three to five-year-old preschool children in Saskatoon,
      Canada. Caries was recorded using the WHO (1987) criteria and a modified scoring
      system(MC) in which questionable lesions (no soft walls or floor) were included
      as carious. Whole stimulated saliva was collected from each subject and S. mutans
      counts were determined (CFU/ml of saliva). Both dft(MC) = 1.03 and dfs(MC) = 1.53
      were significantly different (p < .0001) from dft(WHO) = 0.69 and dfs(WHO) =
      1.17, respectively. The S. mutans count was found to be significantly (p < .001)
      correlated with dft(MC), dfs(MC), dft(WHO) and dfs(WHO). When questionable
      carious lesions are included in caries indices, they appear to remain well
      associated with salivary S. mutans counts.

PMID- 7560366
TI  - Effect of cavity form on the durability of glass ionomer cement restorations in
      primary teeth: a three-year clinical evaluation.
AB  - The effect of cavity form on the durability of glass ionomer cement restorations
      in primary molars was studied in a clinical, intraindividual, three-year
      longitudinal study. Proximal restorations were placed in either a microcavity or
      a modified Black's Class II cavity with rounded internal and external angles. A
      total of twenty-eight pairs were assessed. After two years the cumulative failure
      rate was 16 percent for each of the cavity types and after three years 25 percent
      for the microcavity and 32 percent for the modified Black's Class II cavity. No
      statistical difference was found in the longevity of the restorations placed in
      the two different types of cavities.

PMID- 7560365
TI  - Influence of fluoride in saliva during the early cariogenic changes in the enamel
      of boys and girls.
AB  - In boys and girls cariogenic changes in the dental enamel in relation to fluoride
      (F-) concentrations in stimulated and unstimulated saliva were studied in a six
      month period. Also the use of various types of applications of F- was assessed.
      No difference in the use of F- between boys and girls before and after the
      interval was observed. Also no clear differences were found between boys and
      girls in the levels of F- in both types of saliva, determined at the end of the
      six-month period. The most important finding was that for all children, a
      significantly positive relationship was found between the disappearance of white
      spots turning into sound enamel (regression) and the F-concentration in
      unstimulated saliva. In addition, girls who developed new white spots had higher
      levels of F-, but those who developed new cavities had lower F- levels in both
      types of saliva. Apparently F- can prevent dental caries by acting very early on
      remineralization and demineralization processes in enamel surfaces.

PMID- 7560367
TI  - Traumatic herniation of the buccal fat pad: report of case.
AB  - Traumatic herniation of buccal fat pad in a case of twenty-month-old girl is
      presented. The lesion has been caused by the fall on the tooth brush in the
      mouth, and treated with excision and wound sutures.

PMID- 7560368
TI  - Almost four million children with disabilities.

PMID- 7560369
TI  - Is your pediatric practice keeping pace with the improving picture of dental
      economics?
AB  - A review is provided of dental economics based on national dental expenditure
      data, ADA economic reports and IRS business receipt information. The favorable
      series of economic reports, together with continuing projected decreases in the
      dentist-to-population ratios points to a continuing favorable economic picture
      for pediatric dental practitioners.

PMID- 7560370
TI  - Primary tooth ankylosis: report of case with histological analysis.
AB  - Two primary molars in infraclusion showing clinical and radiographic signs of
      ankylosis, were subject to histological examination by bright field and
      polarization microscopy. The roots revealed signs of ongoing resorptive and
      reparative processes and in some areas dentin with signs of resorption-or repair
      cementum-were fused with simple lamellar or osteonic bone. These results suggest
      that ankylosis of primary molars can result from a disturbance of root
      resorption, with repair processes prevailing over resorptive ones and leading to
      excessive deposition of bone besides cementum-as a consequence of bone-inductive
      properties of dentin.

PMID- 7560371
TI  - Latent fluorides: report of case.
AB  - This case report examines the effects of a long-term exposure to fluoride on the
      teeth of two children who started to drink a highly fluoridated mineral water
      when they were three years and four years of age, respectively. A clinical and
      SEM study was conducted to supply evidence of the harmful effect of fluoride
      ingestion at above optimal levels and to ask for an explicit labeling of drinks
      that contain more than 1 ppm/F.

PMID- 7560372
TI  - Thermographic measurement of temperature change during resin composite
      polymerization in vivo.
AB  - OBJECTIVES: To use the technique of infrared thermography for non-invasive
      monitoring of temperature changes during polymerization of resin composite by
      measuring the infra-red emission from the surfaces of resin composite
      restorations during photocuring. METHODS: In this study 10 patient volunteers had
      resin composite restorations placed in upper incisor teeth and during photocuring
      the temperature rise within the composite was measured using the Thermovision 900
      infra-red scanning system. RESULTS: The results demonstrate that the exotherm is
      almost instantaneous, occurring as soon as the light source is activated and
      rising to a peak at approximately 30 s before levelling off. The measurements
      suggest that a maximum temperature increase of 12 degrees C could occur, although
      this may only be for a short period (< 15 s). CONCLUSION: The range of
      temperature rise measured in this study (mean 5.4 degree C +/- 2.5 degree C)
      would suggest that the pulp may be endangered by the temperature rise which
      occurs during resin composite polymerization in vivo.

PMID- 7560373
TI  - Identification of elderly in particular need: results of a survey undertaken in
      residential homes in the Manchester area.
AB  - OBJECTIVES: This paper aims to identify which groups of elderly people living in
      residential institutions are in particular need of dental care and advice.
      Comparison of different types of residential institution allows identification of
      elderly in greatest need of dental assistance. METHODS: A postal survey of carers
      in 250 residential homes for elderly people in Manchester, UK, was undertaken to
      determine the frequency of dental visits, arrangements for dental care of the
      residents' teeth and denture cleansing and appliance-wearing patterns and, also,
      the carers' knowledge and practice of simple dental and oral maintenance
      procedures for residents. Comparisons were undertaken using the SPSS software
      package of: social service and private homes, large and small homes, homes where
      regular visits were undertaken and those not regularly visited, and also homes
      which maintained records of their clients' dental state with those which did not.
      RESULTS: Residents' oral health tended to be more at risk in smaller or privately
      managed homes, in those where no dentist visited regularly and where no records
      of dental care were kept. CONCLUSION: The dental profession needs to especially
      target homes where care is less well organized, not only to examine and treat
      residents, but also to instruct carers in simple mouth care techniques, in order
      that dental disability in an increasingly dentate population can be minimized.

PMID- 7560374
TI  - SEM characterization of the resin-dentine interface produced in vivo.
AB  - OBJECTIVES: A freeze-fracture technique with critical-point drying has been shown
      to preserve the structure of collagen in demineralized primed dentine in vitro
      (Titley K et al. Am J Dent 1994; 7: 22-26). This study utilized the technique to
      examine the attachment to dentine produced in vivo All-Bond 2 (AB2), Scotchbond
      Multi-Purpose (SBMP) and Prisma Universal Bond 3 (PUB3). METHODS: Eighteen medium
      depth restorations were placed in buccal and/or lingual surfaces of premolar
      teeth (n = 7) scheduled for extraction for orthodontic purposes. After
      extraction, the restored teeth were split transversely by freeze-fracture,
      critical-point dried and examined under SEM. RESULTS: AB2 and SBMP produced
      significant gap-free attachment to dentine showing similar microscopic structural
      features. Resin interdiffusion with collagen fibrils of the intertubular matrix
      was clearly seen. Microspaces, observed at the periphery of the widened tubules
      and among the interdiffused collagen fibrils, suggested incomplete resin
      penetration. Fractures occurring parallel with the interface frequently showed
      detachment in the deepest layers of the hybrid zone. Adhesive gaps were seen at
      the resin-dentine interface, indicating some clinical technique failure. The PUB3
      attachment was generally incomplete, with separation between the primed dentinal
      surface and the composite restoration. Where present, the bonded interface showed
      no evidence of true hybridization. CONCLUSION: Dentine conditioning, as a
      separate step, prior to priming, appears to be an important factor in successful
      resin-dentine attachment. Critical-point drying revealed variations in the degree
      of resin interdiffusion with intertubular collagen, suggesting potential sites
      for bond failure.

PMID- 7560375
TI  - Impregnation by dentine bonding agents into instrumented root-face dentine.
AB  - OBJECTIVES: To examine the penetration of unfilled resin into instrumented root
      face dentine, facilitated by five commercially available dentine bonding agents.
      METHODS: Upper third molar teeth were decoronated, and a given dentine bonding
      agent and resin composite applied to the instrumented root face, according to the
      manufacturer's instructions. A control specimen was similarly prepared but not
      dentine primer was applied prior to resin composite. The teeth were sectioned
      longitudinally and the sectioned surface demineralized and deproteinated.
      Specimens were examined by scanning electron microscopy (SEM) for resin tag
      length and density in different areas of the root face. RESULTS: Specimens
      treated with dentine bonding agent systems exhibited minimum resin penetration of
      peripheral root-face dentine and much longer penetration of resin tags in dentine
      above the pulp chamber. A possible 'hybrid' layer of resin-impregnated dentine
      was observed in all specimens where a dentine bonding agent system had been used
      but was not observed in control specimens. Resin tags were also more sparsely
      observed in control specimens. CONCLUSION: Resin tag penetration is superior in
      both density and length of penetration in dentine overlying and adjacent to the
      pulp chamber, with shorter and sparser penetration exhibited in peripheral root
      face dentine. The possible clinical implications of these observations are
      discussed.

PMID- 7560376
TI  - A delayed hypersensitivity reaction to dentine primer in the guinea-pig.
AB  - OBJECTIVE: This study was undertaken to examine the possibility of a delayed
      hypersensitivity reaction or contact dermatitis occurring in the guinea-pig in
      response to methacrylate derivatives used as experimental dentine primers.
      METHODS: The dentine primers 2-HEMA, GM, MA and MMA were tested in a guinea-pig
      maximization test. RESULTS: All the dentine primers tested produced positive
      delayed hypersensitivity reactions in the guinea-pig. MMA produced the most
      severe reaction. CONCLUSION: It is concluded that in the clinical situation,
      clinicians and other members of the dental team should be aware of the need for
      careful handling of the dentine primers tested.

PMID- 7560377
TI  - Zonal coulometric analysis of the corrosion resistance of dental alloys.
AB  - OBJECTIVES: The corrosion resistance of a series of 51 dental alloys and pure
      metals was evaluated by coulometric analysis. METHODS: The method consisted of
      dividing the anodic polarization curves into three separate zones: zone I, from
      the open-circuit potential (after 24 h immersion) up to +300 mV (SCE): zone II,
      from 300 mV to 700 mV (SCE): zone III, +700 mV to 1000 mV (SCE). The surfaces
      below the curves are integrated for each zone and the results expressed in
      millicoulombs (mC). RESULTS AND CONCLUSIONS: Although the intensity of
      degradation in the mouth may vary from patients to patient, we think that a
      potential danger may occur in zones I and II in particular. Coulometric analysis
      reveals that: (i) the alloys for the porcelain-fused-to metal (PFM) technique
      have a better corrosion resistance (2.58 mC on average for the sum of the three
      zones, against 283.7 mC for conventional alloys): (ii) the elements Cu, Ag and Ni
      reduce the corrosion resistance of gold-based alloys: (iii) within the same
      class, single-phase alloys resist better than two-phase alloys.

PMID- 7560378
TI  - The effect of preparation conditions of acrylic denture base materials on the
      level of residual monomer, mechanical properties and water absorption.
AB  - OBJECTIVES AND METHODS: The curing of several commercial powder/liquid mixtures
      of acrylic denture base materials was carried out at different temperatures and
      curing times. The levels of residual monomer, tensile strength, percentage
      elongation before break and water absorption were measured. RESULTS AND
      CONCLUSION: It was found that the level of residual monomer determined by gas
      liquid chromatography decreased with curing time and temperature increase. At the
      same time, the tensile strength was improved and water absorption decreased.

PMID- 7560379
TI  - Contamination of titanium castings by aluminium oxide blasting.
AB  - OBJECTIVES: It is desirable that the surfaces of surgical implants be
      uncontaminated by foreign materials to avoid untoward tissue reactions, and grit
      blasting is widely assumed to leave clean metal surfaces. SEM examination and X
      ray microanalysis of a recovered 'pure' titanium implant casting that was
      associated with tissue breakdown revealed embedded particles of alumina. The
      casting had been cleaned of investment by blasting with alumina grit. METHODS: A
      variety of treatments of cast titanium plates was used: (a) to establish that the
      observed aluminium was due to the blasting grit, and (b) to determine whether
      removal of investment could be achieved effectively by other means. SEM
      examination and X-ray microanalysis were used. RESULTS: The detected aluminium
      was associated with embedded fragments identified as coming from the blasting
      grit. Acid-pickling and mechanical (rotary instrument) trimming produced
      minimally contaminated surfaces. CONCLUSIONS: Whilst unproven, the presence of
      the alumina is viewed with great concern as a possible causative agent in the
      observed tissue breakdown and procedures avoiding alumina blasting are
      recommended as a precautionary measure.

PMID- 7560380
TI  - Why is biomedical research like a washing machine?: A question whose time has
      come.

PMID- 7560381
TI  - The status of dental student research in Turkey.

PMID- 7560382
TI  - Seventy-five and growing.

PMID- 7560383
TI  - Some reflections on the influence of Neil Jenkins on dental education and
      research.

PMID- 7560384
TI  - Consideration of possible biologic mechanisms of fluorosis.

PMID- 7560385
TI  - A topographical and ultrastructural study of sensory trigeminal nerve endings in
      the rat temporomandibular joint as demonstrated by anterograde transport of wheat
      germ agglutinin-horseradish peroxidase (WGA-HRP).
AB  - To extend our previous light microscopic observations concerning the distribution
      of trigeminal sensory nerves in the synovium of the rat temporomandibular joint,
      we investigated the detailed distribution and fine structure of sensory nerve
      endings at the light and electron microscopic level by the anterograde transport
      method using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into
      the trigeminal ganglion. At the light microscopic level, HRP-labeled nerve fibers
      were observed in the joint capsule and peripheral portion of the disc. The
      anterior portion of the disc was more densely innervated than the posterior
      portion, while no nerves were found in the central portion. At the electron
      microscopic level, HRP reaction products were observed intra-axonally in the
      thinly myelinated (A delta) and unmyelinated (C) axons in the anterior portion of
      the joint capsule, and were also localized in the extracellular space surrounding
      the unmyelinated fibers and terminals. In the subsynovial layer of the synovial
      membrane, the majority of labeled axons located near blood vessels or among the
      collagenous fibrils were covered by Schwann cell sheaths, although some naked
      axon terminals without sheaths were also found. These unsheathed terminals
      contained mitochondria, small clear vesicles, and large granular vesicles, and
      were close to the synovial A and/or B cells near the joint cavity. The minimum
      distance between the terminals and synovial cells was 75 nm. This is the first
      demonstration of trigeminal sensory nerve terminals close to synovial lining
      cells or joint cavity and suggests that neuropeptides such as substance P may be
      released close to the synovial lining cells or joint cavity.

PMID- 7560386
TI  - Salivary amylase promotes adhesion of oral streptococci to hydroxyapatite.
AB  - Recent studies have demonstrated that several species of oral streptococci, such
      as Streptococcus gordonii, bind soluble salivary alpha-amylase. The goal of the
      present study was to determine if amylase immobilized onto a surface such as
      hydroxyapatite can serve as an adhesion receptor for S. gordonii. Initially,
      human parotid saliva was fractionated on Bio-Gel P60, and fractions were screened
      for their ability to promote adhesion of S. gordonii to hydroxyapatite. Fractions
      containing alpha-amylase and proline-rich proteins promoted the adhesion of [3H]
      labeled S. gordonii to hydroxyapatite. Similar findings were obtained with
      purified amylase and acidic proline-rich protein 1 (PRP1). Incubation of S.
      gordonii G9B in the presence of starch and maltotriose increased the binding of
      this strain to amylase-coated hydroxyapatite, while the adhesion of S. sanguis
      10556 to amylase-coated hydroxyapatite was not affected by these saccharides.
      These results suggest that amylase may serve as a hydroxyapatite pellicle
      receptor for amylase-binding streptococci. Furthermore, starch and starch
      metabolites may enhance the adhesion of amylase-binding streptococci to amylase
      in dental pellicles to augment the formation of dental plaque.

PMID- 7560387
TI  - Volatile fatty acids, metabolic by-products of periodontopathic bacteria, inhibit
      lymphocyte proliferation and cytokine production.
AB  - Short-chain fatty acids are a major by-product of anaerobic metabolism and can be
      detected in gingival fluid from periodontal pockets. Since most T cells are
      present subjacent to the pocket epithelium in conjunction with the plasma cells,
      it is important to know how these T cells are affected by short-chain fatty acids
      produced by subgingival plaque. The purpose of this study is to examine the
      effects of extracellular metabolites from periodontopathic bacteria on the
      proliferation and cytokine production of mouse splenic cells as a potential
      mechanism of imbalance among host-microbial interactions. A low-molecular-weight,
      heat-stable agent present in the two-day culture filtrate of Porphyromonas
      gingivalis, Prevotella loescheii, and Fusobacterium nucleatum significantly
      depressed Con A- and LPS- induced cell proliferation. To determine whether short
      chain fatty acids present in the filtrate could account for the depression, we
      tested extracted volatile and non-volatile fatty acids for their effects on
      mitogenic activity. The volatile fatty acids extracted from immunosuppressive
      supernatants greatly inhibited T- and B- cell proliferation. Among these volatile
      fatty acids, butyric, propionic, valeric, and isovaleric acids impaired cell
      proliferation dose-dependently. From gas-liquid chromatographic analysis data, it
      is suggested that immuno-inhibitory activities in culture filtrates are mainly
      attributable to butyric and isovaleric acids in P. gingivalis, to propionic,
      butyric, and isovaleric acids in P. loescheii, and to butyric acid in F.
      nucleatum. Furthermore, these fatty acids significantly depressed interleukin 2
      (IL-2), IL-4, IL-5, IL-6, and IL-10 production by Con A-stimulated splenic-T
      cells dose-dependently.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560388
TI  - Alkaline phosphatase activity in the periodontal ligament and gingiva of the rat
      molar: its relation to cementum formation.
AB  - Alkaline phosphatase (ALP) is a glycoprotein thought to be involved in processes
      leading to mineral formation in tissues like bone and cementum. In the rat molar
      periodontium, several regions are associated with the formation of cementum
      (periodontal ligament, inner part of the gingiva), whereas other areas are not
      (e.g., the outer part of the gingiva just beneath the outer oral epithelium). In
      an attempt to establish how the spatial distribution of ALP activity relates to
      cementum formation, we assessed the activity of the enzyme quantitatively in the
      periodontium of the rat maxillary molars, by using the indoxyl-tetrazolium salt
      method. It appeared that the distribution of enzyme activity in the ligament was
      heterogeneous, indicating local variations in the phosphate household. Highest
      activity was found in areas related to mineralization, adjacent to the alveolar
      bone and cementum. Enzyme activity was higher adjacent to cellular cementum than
      to acellular cementum. With respect to acellular cementum, a highly significant
      positive correlation was found between ALP activity and cementum thickness, which
      indicates a close relationship between local phosphate production and cementum
      formation rate. An interesting observation in the connective tissue of the
      gingiva mesial to the first molar was a sharp demarcation between an ALP-positive
      inner part, adjacent to the tooth, and an ALP-negative outer part, underneath the
      outer oral epithelium. In the interdental gingiva, the entire connective tissue
      proved positive for the enzyme, suggesting that this region consists of the
      combined inner gingival parts of two adjacent teeth.

PMID- 7560389
TI  - Inhibition of prostaglandin E2 and interleukin 1-beta production by low-power
      laser irradiation in stretched human periodontal ligament cells.
AB  - It is well-known that orthodontic treatment usually causes some discomfort and
      pain to the patients. Recently, it has been reported that low-power laser
      irradiation is effective in reducing the pain accompanying tooth movement.
      However, the mechanism of such pain relief cannot be elucidated. Since high
      levels of prostaglandin (PG) E2 and interleukin (IL)-1 beta are found in the
      periodontal ligament (PDL) during tooth movement, and both factors are involved
      in the induction of pain, the effects of low-power laser irradiation on PGE2 and
      IL-1 beta production in stretched human PDL cells were studied in vitro. The PDL
      cells, derived from healthy premolars extracted for orthodontic treatment, were
      utilized for experiments. Cells were seeded in flexible-bottomed culture plates,
      and the bottom of each plate was elongated (18% increase) under vacuum at 6
      cycles per min for 1, 3, or 5 days. The stretched cells were irradiated with a Ga
      Al-As low-power diode laser (60 mW) once a day for 3, 6, or 10 min (from 10.8 to
      36.0 J) for 1, 3, or 5 days. PGE2 and IL-1 beta levels in the medium were
      measured by radioimmunoassay. In response to mechanical stretching, human PDL
      cells showed a marked elevation in PGE2 production in a time-dependent manner. IL
      1 beta production was also elevated, but this remained constant. The increase in
      PGE2 production was significantly inhibited by laser irradiation in a dose
      dependent manner. The increase in IL-1 beta production was also significantly
      inhibited by laser irradiation, although the inhibition was only
      partial.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560390
TI  - Genetic covariance structure of incisor crown size in twins.
AB  - Previous studies of tooth size in twins and their families have suggested a high
      degree of genetic control, although there have been difficulties separating the
      various genetic and environmental effects. A genetic analysis of variation in
      crown size of the permanent incisors of South Australian twins was carried out,
      with structural equation modeling used to determine the relative contributions of
      genetic and environmental factors. Maximum mesiodistal crown dimensions of
      maxillary and mandibular permanent incisors were recorded from dental models of
      298 pairs of twins, including 149 monozygous (MZ) and 149 dizygous (DZ) pairs.
      The analysis revealed that: (i) an adequate fit required additive genetic and
      unique environmental components; (ii) augmenting the model with non-additive
      genetic variation did not lead to a significant improvement in fit; (iii) there
      was evidence of shared environmental influences in the upper central incisors of
      males; (iv) the additive genetic component constituted a general factor loading
      on all eight teeth, with group factors loading on antimeric pairs of teeth; (v)
      unique environmental effects were mostly variable-specific; (vi) most factor
      loadings on antimeric tooth pairs could be constrained to be equal, indicating a
      symmetry of genetic and environmental influences between left and right sides;
      and (vii) estimated heritability of the incisor mesiodistal dimensions varied
      from 0.81 to 0.91.

PMID- 7560391
TI  - Infants' fluoride intake from drinking water alone, and from water added to
      formula, beverages, and food.
AB  - In infants, the majority of total ingested fluoride is obtained from water,
      formula and beverages prepared with water, baby foods, and dietary fluoride
      supplements. Few studies have investigated the distribution of fluoride intake
      from these sources among young children at risk for dental fluorosis. The purpose
      of this study was to assess estimated water fluoride intake from different
      sources of water among a birth cohort studied longitudinally from birth until age
      9 months. Parental reports were collected at 6 weeks, 3 months, 6 months, and 9
      months of age for water, formula, beverage, and other dietary intake during the
      preceding week. Fluoride levels of home and child-care tap and bottled water
      sources were determined. This report estimates daily quantities of fluoride
      ingested only from water--both by itself and used to reconstitute formula,
      beverages, and food. Daily fluoride intake from water by itself ranged to 0.43
      mg, with mean intakes < 0.05 mg. Water fluoride intake from reconstitution of
      concentrated infant formula ranged to 1.57 mg, with mean intakes by age from 0.18
      to 0.31 mg. Fluoride intake from water added to juices and other beverages ranged
      to 0.67 mg, with means < 0.05 mg. Estimated total daily water fluoride intake
      ranged to 1.73 mg fluoride, with means from 0.29 to 0.38 mg.

PMID- 7560392
TI  - Relation between clinical dental status and subjective impacts on daily living.
AB  - Although clinical dental status has weak correlations with subjective impacts,
      some of them are significant. Those variables which had significant correlations
      could be used as a starting point to understand clinical and social
      characteristics of people who experience dental problems. This is indeed the
      basis for the current research. The study compares psychosocial impacts on the
      quality of people's life with their respective oral status. To that end, a socio
      dental indicator, the 'Dental Impact of Daily Living' (DIDL), involving five
      dimensions, together with a scale which assesses dimension impacts, was
      developed. The resulting instrument was validated and the reliability tested. The
      instrument generates a total final score, in addition to scores for each
      dimension. The method was tested in Brazil on a sample of 662 people, aged from
      35 to 44 years, of two social classes, both sexes, and with three different
      levels of dental caries status or with a full upper denture. To test whether DIDL
      discriminated between groups with different levels of subjective impact, we
      analyzed how oral status, social class, and gender varied according to impacts.
      Different levels of oral status had different impacts on people's daily life. On
      the basis of the results, it is reasonable to suggest that oral status and social
      and psychological dimensions should be considered simultaneously when in
      assessment of people's dental needs.

PMID- 7560393
TI  - Mercury vaporization from amalgams with varied alloy compositions.
AB  - The fact that mercury is released from dental amalgam restorations after abrasion
      provides a source of continued controversy over the safe use of this material.
      Studies have shown that the amount and rate of mercury release vary for different
      amalgam products. The objective of this study was to determine how alloy
      composition affects mercury vaporization from experimental amalgams with similar
      alloy particle size and shape and percent residual mercury. An hypothesis to be
      tested was that mercury release is dependent upon the concentration of tin in the
      silver-mercury matrix phase of the amalgam. Seven spherical amalgam alloys (two
      low-copper and five high-copper) were made by a dental manufacturer (Tokuriki
      Honten, Japan). Trituration conditions were adjusted so that all set amalgams had
      the same residual Hg (47.3%). ADA-type amalgam cylinders were aged for 14 days at
      37 degrees C, then lightly wet-abraded on #600 silicon carbide, dried, and placed
      into a tube through which air was blown at a rate of 750 mL/min. Mercury
      vaporization was monitored with a gold film analyzer (Jerome 411) for 30 min.
      Total Hg release was determined by integration. We analyzed polished specimens
      via electron microprobe to determine composition, volume fraction of silver
      mercury matrix (gamma 1), and amount of tin in the gamma 1. The results showed a
      strong negative correlation (r2 = 0.941) between the log of total mercury
      released and the amount of tin in the gamma 1. The effect of alloy composition,
      specifically the presence or absence of zinc in the amalgam, could not be
      definitively determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560394
TI  - Fracture toughness of experimental dental composites aged in ethanol.
AB  - Fracture toughness (KIc) is an intrinsic property which may be related to the
      ability of a restorative material to resist fracture and abrasion. This property
      may change for a dental composite restorative due to the effects of various oral
      solvents. The hypothesis to be tested was that aging in ethanol would cause a
      reduction in the fracture toughness of dental composites, and that the extent of
      this reduction might be dependent upon certain compositional variables. The
      fracture toughnesses of three series of experimental composites with various
      degrees of conversion, filler volume, and percent of silane-treated fillers were
      compared after the composites were aged for periods of one month and six months
      in 75% ethanol/water, a solvent which serves as a food-simulating liquid. An
      unfilled Bis-GMA/TEGDMA resin served as the control. All composites, with the
      exception of one subjected to a post-light-curing heat treatment, experienced a
      significant reduction (from 30 to 56%) in KIc after being aged in 75% ethanol for
      six months. A similar reduction in KIc of 58% for the unfilled resin suggested
      that the reduction for the composites was due to a weakening of the resin matrix,
      which facilitated crack propagation. A simultaneous reduction in microhardness
      was also demonstrated. One month of aging in ethanol also produced large
      reductions in KIc for specimens with insufficient cure and minimal filler volume,
      suggesting that the properties of the resin matrix predominated for these
      composites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560395
TI  - Efficacy of the FDA selection criteria for radiographic assessment of the
      periodontium.
AB  - The diagnosis of periodontitis is generally made on the basis of a clinical
      examination supported by radiographic evidence of bone loss. Recent guidelines
      promulgated by the US Food and Drug Administration recommend that periapical
      radiographs be ordered on the basis of clinical signs and symptoms indicating the
      probable presence of disease. This study evaluated the effectiveness of the FDA
      Guidelines for ordering radiographs for new adult dental patients as related to
      assessment of the periodontal condition of the patient. We examined 490 patients
      and determined the periapicals needed to supplement the posterior bitewings based
      upon the patient's clinical findings. We measured the reduction in the number of
      radiographs ordered as well as the extent of missed alveolar and furcation bone
      loss resulting from the use of the selected set of radiographs compared with a
      complete set. Four hundred thirty-three subjects had at least one clinical sign
      of periodontitis present in their mouths, and 264 demonstrated radiographic
      evidence of alveolar bone loss. Of the 460 subjects on whom periodontal probing
      was conducted, two-thirds demonstrated periodontal probing depths in excess of 3
      mm; almost half showed evidence of bleeding upon probing. Individuals with
      clinical signs of periodontitis had, on average, 10 periapicals ordered--more
      than twice the number as those with no sign of periodontitis. Of the 2,415 teeth
      with radiographic findings of proximal or furcal bone loss, 152 sites of bone
      loss (6%) were missed when the selected set of films plus the posterior bitewings
      was used.

PMID- 7560396
TI  - Prevention and early treatment in orthodontics: a perspective.

PMID- 7560397
TI  - The prevalence of dental anxiety in children from low-income families and its
      relationship to personality traits.
AB  - The prevalence of dental anxiety and the association between dental anxiety and
      personality traits were examined in a population-based sample of 895 US urban
      children, from 5 to 11 years of age, from low-income families. Dental anxiety was
      reported by the child using the Dental Subscale (DS) of the Children's Fear
      Survey Schedule, and behavioral problems and personality traits were evaluated by
      parent report on the Child Behavior Checklist (CBCL). Mean DS scores were 31.1
      (SD = 10.3) for boys and 34.3 (SD = 11.0) for girls. CBCL score means were 33.3
      (SD = 23.2) for boys and 28.5 (SD = 19.1) for girls. The hypothesized
      relationship between DS and CBCL scores in this population was not demonstrated.

PMID- 7560398
TI  - Effects of protein deficiency and diet consistency on the parotid gland and
      parotid saliva of rats.
AB  - Protein deficiency results in an increased susceptibility to dental caries,
      suggesting that oral host-defense properties are compromised. An important
      component of oral host defense is salivary gland function, which is affected by
      both protein deficiency and diet consistency. This study describes the effects on
      rat parotid gland growth and secretory function induced by feeding rats diets of
      normal (20%) or moderately low (7%) protein content, provided in either a
      powdered or solid form. In addition, since protein deficiency may result in a
      secondary zinc deficiency which, in turn, may affect salivary gland function, the
      effects of these diets on liver zinc concentration were also measured. From 22 to
      47 days of age, rats (18/group) were fed the following diets: normal protein,
      powdered; normal protein, solid; low protein, powdered; and low protein, solid.
      With each diet consistency, liver zinc was higher for the normal protein group.
      Within each protein level, liver zinc was higher for the solid diet. This latter
      observation suggests that food mastication and the resultant stimulation of
      salivary gland function may also play a role in zinc metabolism. With the normal
      protein diet, parotid gland weight was higher for the solid diet; with the low
      protein diet, parotid gland weight was similar for both consistencies and did not
      differ from that of the group fed the "normal protein, powdered" diet. For both
      consistencies, parotid saliva protein concentration was greater for malnourished
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560399
TI  - Definitive vs. exploratory periodontal trials: a survey of published studies.
AB  - Definitive and exploratory randomized controlled trials (RCTs) have different
      goals as well as different design and analysis characteristics. The goal of
      definitive studies is to provide unequivocal evidence of a treatment's tangible
      benefit to the patient; a pre-trial-specified hypothesis is tested by use of a
      pre-trial-specified method. The goal of exploratory studies is to elucidate
      biological treatment mechanisms, to identify promising treatments, and to
      generate hypotheses for definitive studies; multiple hypotheses are evaluated to
      extract as much information from the data as possible. The purposes of this study
      were: (1) to survey selected design and analysis characteristics of randomized
      controlled periodontal trials published between 1988 and 1992 (n = 86), and (2)
      to classify trials as exploratory or definitive studies. The peridontal RCTs
      surveyed were typical of exploratory studies whose primary goal was to elucidate
      biological treatment mechanisms. Trial reports indicated the testing of multiple
      hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of
      biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in
      67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and
      design and analysis characteristics (e.g., an absence of masking in 57 out of 86
      trials) were also typical of exploratory studies which strive to obtain quick
      answers (short duration) at a low cost (small sample size; accept bias for
      increased efficiency and a lower cost). No definitive trials were
      identified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560400
TI  - Full- vs. partial-mouth disinfection in the treatment of periodontal infections:
      short-term clinical and microbiological observations.
AB  - In a standard periodontal treatment strategy with consecutive root planings (per
      quadrant at a one- to two-week interval), re-infection of a disinfected area
      might occur before completion of the treatment. This study examines, both
      clinically and microbiologically, whether a full-mouth disinfection within 24
      hours significantly improves the outcome of periodontal treatment. Ten patients
      with advanced chronic periodontitis were randomly allocated to a test and a
      control group. The patients from the control group received scalings and root
      planings as well as oral hygiene instructions per quadrant at two-week intervals.
      Full-mouth disinfection in the test group was sought by the removal of all plaque
      and calculus (in two visits within 24 hours). In addition, at each of these
      visits, the tongue was brushed with a 1% chlorhexidine gel for one min and the
      mouth rinsed with a 0.2% chlorhexidine solution for two min. Furthermore,
      subgingival chlorhexidine (1%) irrigation was performed in all pockets. The
      recolonization of the pockets was retarded by oral hygiene and 0.2% chlorhexidine
      rinses during two weeks. The clinical parameters were recorded, and plaque
      samples were taken from the right upper quadrant at baseline and after one and
      two months. The test group patients showed a significantly higher reduction in
      probing depth for deep pockets at both follow-up visits (p < 0.05). At the one
      month visit, differential phase-contrast microscopy revealed significantly lower
      proportions of spirochetes and motile rods in the test group (p = 0.01).
      Culturing showed that the test group harbored significantly fewer pathogenic
      organisms at one month (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560401
TI  - Long-term exposure to fluoride in drinking water and sister chromatid exchange
      frequency in human blood lymphocytes.
AB  - The genetic toxicity of fluoride has been investigated extensively by various
      test systems. However, results obtained have been inconsistent. Fluoride has been
      reported to be non-genotoxic, genotoxic, and synergistic or antagonistic with
      certain mutagens. To date, there are no published human studies on the
      genotoxicity of fluoride. The purpose of this investigation was to determine
      genotoxic risks of long-term exposure to various concentrations of fluoride in
      drinking water in humans with normal or inadequate nutrition. Six groups of
      subjects with either normal or inadequate nutritional intakes were selected from
      areas of approximately 0.2, 1.0, or 4.8 ppm (10.5, 52.6, or 252.6 mumol/L)
      fluoride in water. The subjects had been continuous residents in the area for at
      least 35 years. Samples of drinking water, plasma, and urine were analyzed for
      fluoride content. Blood lymphocytes were examined to determine the frequency of
      sister chromatid exchange (SCE). Blood chemistry and electrolytes were also
      analyzed. The results showed that average daily fluoride intake as well as urine
      and plasma fluoride levels increased with increase in the fluoride content of the
      drinking water. The blood chemistry and electrolyte values were within the normal
      range for all populations, but several parameters were significantly different.
      While the numerical differences were small, the subjects with low fluoride in the
      water (0.11 and 0.23 ppm or 5.8 and 12.1 mumol/L) had significantly higher SCE
      frequencies than those with higher fluoride exposures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7560402
TI  - Fluoride reduces bone strength in older rats.
AB  - In response to recent concerns about the effect of water fluoridation on hip
      fracture rates, we studied the influence of fluoride intake on bone strength.
      Four groups of rats were fed a low-fluoride diet ad libitum and received 0, 5,
      15, or 50 ppm of fluoride in their drinking water. Animals were euthanized after
      3, 6, 12, or 18 months of treatment. Mechanical strength of the right femur was
      measured by three-point bending. Fluoride content for the left femur was
      measured, and static histomorphometric measurements were made on a lumbar
      vertebra. Femoral failure load was not significantly decreased in rats treated
      for 3 and 6 months, but was decreased as much as 23% in rats treated 12 and 18
      months at 50 ppm fluoride. Extrapolation from regression equations predicted that
      older rats lose 36% of femoral bone strength when bone fluoride content is
      increased from 0 to 10,000 ppm, while younger rats will lose only 15%. Thus, the
      decreased strength appeared to be due to the combined effects of fluoride intake
      and age on bone tissue and was not associated with a decrease in bone density or
      mineralization defects. There were only small effects of fluoride on bone
      histomorphometry. Fluoride intake at high levels had no negative effects on bone
      mineralization. Fluoride intake was associated with slight increases in
      trabecular bone volume and trabecular thickness, but these effects could not be
      demonstrated consistently. The mechanism by which large amounts of fluoride
      affect bone strength more severely in older animals is unknown.

PMID- 7560403
TI  - Computer modeling of the effects of chewing sugar-free and sucrose-containing
      gums on the pH changes in dental plaque associated with a cariogenic challenge at
      different intra-oral sites.
AB  - Variation in salivary access to different intra-oral sites is an important factor
      in the site-dependence of dental caries. This study explored, theoretically, how
      access is modified by chewing sugar-free and sugar-containing gums. A finite
      difference computer model, described elsewhere, was used. This allowed for
      diffusion and/or reaction of substrate, acid product, salivary buffers, and fixed
      acid groups. Site-dependent saliva/plaque exchange was modeled in terms of a 100
      microns-thick salivary film covering the plaque (a) flowing directly from the
      salivary ducts, (b) flowing from the intra-oral salivary pool, or (c) exchanging
      with the pool. Computed flow-velocities or rates of exchange were based on
      previous intra-oral measurements. The model was also tested against an in vitro
      study conducted by two of the authors. In addition, the three proposed models of
      saliva/plaque interaction were compared, and the effect of salivary film
      thickness investigate. Results suggested that: (1) although sugar-free gum chewed
      during a cariogenic challenge causes a rapid rise in plaque pH, sucrose
      containing gums cause the pH, after a temporary rise resulting from increased
      salivary flow, to stay low for an extended period; (2) the computer model
      reproduced in vitro tests reasonably well; (3) although the three models of the
      plaque/saliva interaction start from different assumptions, two lead to closely
      related predictions; and (4) increasing the assumed salivary film thickness by a
      large amount (e.g., from 50 to 200 microns) caused no change in modeled Stephan
      curves, as long as these changes were accompanied by appropriate reductions in
      film velocity, in accord, theoretically, with the practical clearance data.

PMID- 7560404
TI  - Architecture of the human pterygoid muscles.
AB  - Muscle force is proportional to the physiological cross-sectional area (PCSA),
      and muscle velocity and excursion are proportional to the fiber length. The
      length of the sarcomeres is a major determinant of both force and velocity. The
      goal of this study was to characterize the architecture of the human pterygoid
      muscles and to evaluate possible functional consequences for muscle force and
      muscle velocity. For the heads of the lateral and medial pterygoid, the length of
      sarcomeres and of fiber bundles, the PCSA, and the three-dimensional coordinates
      of origin and insertion points were determined. Measurements were taken from
      eight cadavers, and the data were used as input for a model predicting sarcomere
      length and active muscle force as a function of mandibular position. At the
      closed-jaw position, sarcomeres in the lateral pterygoid (inferior head, 2.83 +/-
      0.1 microns; superior head, 2.72 +/- 0.11 microns) were significantly longer than
      those in the medial pterygoid (anterior head, 2.48 +/- 0.36 microns; posterior
      head, 2.54 +/- 0.38 microns). With these initial lengths, the jaw angle at which
      the muscles were capable of producing maximum active force was estimated to be
      between 5 degrees and 10 degrees. The lateral pterygoid was characterized by
      relatively long fibers (inferior, 23 +/- 2.7 mm; superior, 21.4 +/- 2.2 mm) and a
      small PCSA (inferior, 2.82 +/- 0.66 cm2; superior, 0.95 +/- 0.35 cm2), whereas
      the medial pterygoid had relatively short fibers (anterior, 13.5 +/- 1.9 mm;
      posterior, 12.4 +/- 1.5 mm) and a large PCSA (anterior, 2.47 +/- 0.57 cm2;
      posterior, 3.53 +/- 0.97 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560405
TI  - Contributions of facial morphology, age, and gender to EMG activity under biting
      and resting conditions: a canonical correlation analysis.
AB  - Theoretical studies suggest that facial morphology may confer a mechanical
      advantage to particular individuals during force production, but not during rest.
      However, prior studies on the relationship between facial morphology and EMG
      suffer from various methodological limitations. We examined the hypothesis that
      facial morphology variables contribute significantly and meaningfully to the
      variance in masticatory muscle EMG when subjects produce specific levels of
      interocclusal force, but not when subjects are at rest. Measures of facial
      morphology included gonial angle, ramus height, and maxillary height, as
      determined from lateral cephalograms. EMG data were obtained from surface
      electrodes placed on masseter and temporalis sites. Subjects (N = 96) sat in a
      darkened, sound-attenuated room while they watched a seven-minute segment of a
      movie. EMG activity obtained during the last two minutes was used as a baseline
      period. Using the central incisors, subjects then provided five different force
      levels ranging from 6.5 to 48 lb in random order on a bite-force device while EMG
      data were collected. A canonical correlation analysis, performed on the set of
      predictor variables (age, gender, and facial morphology measurements) and the set
      of criterion variables (EMG data), showed a significant canonical correlation
      between the two variable sets while biting, but not at rest. Age, but not the
      facial morphology variables, was highly related to the canonical
      variate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560406
TI  - Evidence for the role of nitric oxide in the circulation of the dental pulp.
AB  - Many authors have studied the hemodynamics of the dental pulp; however, there are
      scarcely any data regarding the involvement of the L-arginine/nitric oxide
      pathway in the regulatory mechanism. Thus, we have examined the physiological
      effects of (1) NG-nitro-L-arginine as an inhibitor of nitric oxide synthesis and
      (2) the nitric oxide donor 3-morpholinosydnonimine on blood flow and vascular
      resistance in the canines of anesthetized cats to study the potential involvement
      of nitric oxide in the regulation of dental vascular homeostasis. Mean arterial
      blood pressure, heart rate, blood gases, pH, cardiac output, and tissue blood
      flow were determined prior to and 15 min after i.v. administration of either NG
      nitro-L-arginine (30 mg/kg, n = 9) or 3-morpholinosydnonimine (1 mg/kg, n = 7).
      Blood flow was measured by radioactive-labeled microspheres. There were no
      significant differences in baseline parameters between the two groups of cats.
      The dental pulp blood flow decreased to 53 +/- 13% (p < 0.01) of the control
      level after NG-nitro-L-arginine administration, while it decreased only slightly
      (to 82 +/- 12%) after 3-morpholinosydnonimine administration. The dental pulp's
      vascular resistance increased to 367 +/- 69% (p < 0.01) of the control level
      after NG-nitro-L-arginine, while it decreased to 73 +/- 10% (p < 0.05) of control
      after 3-morpholinosydnonimine. We found that the L-arginine/nitric oxide pathway
      plays an important role in the regulation of pulpal blood circulation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7560407
TI  - Properties of Ca(2+)-dependent K+ channels of human gingival fibroblasts.
AB  - Cells in the oral cavity are normally exposed to different temperatures. Ion
      transport systems are influenced by temperature in other tissues: In particular,
      changes in intracellular K+ ion can affect cell growth and synthesis of
      macromolecules. The purpose of this investigation was to identify K+ channels in
      human gingival fibroblast cells and analyze the effect of temperature on their K+
      conduction properties. Ca(2+)-dependent K+ channels with a large conductance (125
      pS in symmetrical K(+)-rich solutions) were identified in human gingival
      fibroblasts and studied by the patch-clamp technique. The open probability of the
      channels varied with membrane potential between +40 and -100 mV. When the bath
      temperature was decreased from 40 to 4 degrees C, channel conductance was
      reduced, but the mean open time of the channels was increased. The activation
      energies for the conductance and the reciprocal of the mean open time were
      estimated to be 9.1 and 22.9 kJ/mol, respectively. These values are lower than
      those reported for these and other types of channels in cells from other tissues.
      The open probability of the channels was nearly constant in the temperature range
      studied. These results suggest that the properties of Ca(2+)-dependent K+
      channels of gingival fibroblasts remain relatively unchanged when the cells are
      exposed to a wide range of temperatures.

PMID- 7560408
TI  - Response of L-929 fibroblasts, human gingival fibroblasts, and human tissue mast
      cells to various metal cations.
AB  - Recent data suggest that under certain conditions, various metal cations are
      released from dental alloys. These ions may produce adverse effects in various
      cell types in vivo. In this study, the cytopathogenic effects of 13 metal cations
      on murine L-929 fibroblasts, human gingival fibroblasts, and human tissue mast
      cells were analyzed in vitro. Several metal cations (dose range, from 0.0033 to
      1.0 mmol/L) were found to induce dose-dependent inhibition of 3H-thymidine
      incorporation into cultured fibroblasts. The rank order of potency (lowest
      observed effect level, LOEL) for L-929 fibroblasts was: Ag+ > Pt4+ > Co2+ > In3+
      > Ga3+ > Au3+ > Cu2+ > Ni2+ > Zn2+ > Pd2+ > Mo5+ > Sn2+ > Cr2+. A similar rank
      order of potency was obtained for primary human gingival fibroblasts: Pt4+ > Ag+
      > Au3+ > In3+ > Ga3+ > Ni2+ > Co2+ > Zn2+ > Cu2+ > Cr2+ > Pd2+ > Mo5+ > Sn2+. In
      primary human mast cells, Ag+ and Au3+ caused dose-dependent toxic histamine
      release, whereas the other metal cations were ineffective over the dose range
      tested. To investigate the mechanism of metal cation-induced effects, we
      performed DNA as well as electron microscopic analyses on cultured fibroblasts.
      Both the DNA pattern and the ultrastructure of L-929 cells and gingival
      fibroblasts after exposure to cytopathogenic metal cations revealed signs of
      necrosis but no signs of apoptosis. Together, our data provide evidence that
      various metal cations produce dose-dependent cytopathogenic effects in distinct
      cell types, including human gingival fibroblasts and human tissue mast
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560409
TI  - Cellular response to metallic ions released from nickel-chromium dental alloys.
AB  - Concerns exist over the potential release of elevated levels of metal ions such
      as Ni and Be from Ni-Cr dental casting alloys, due to their susceptibility to
      accelerated corrosion. In this investigation, we evaluated the release of metal
      ions from four commercial Ni-Cr alloys, representing a range of compositions, in
      three-day cell culture tests. Metal ion release, as measured by atomic absorption
      spectroscopy, was correlated to changes in cellular morphology, viability, and
      proliferation. The results showed that the test alloys and their corrosion
      products did not affect cellular morphology or viabilities, but did decrease
      cellular proliferation. The types and amounts of metal ions released, which
      corresponded to the alloys' reported surface and corrosion properties, also
      correlated to observed decreases in cellular proliferation after 72 h. Neptune,
      which caused the smallest decrease in cellular proliferation as compared with
      control cells, released the lowest amount of corrosion products, due to its
      corrosion-resistant, high-Cr-Mo-containing, homogeneous surface oxide. The other
      test alloys, which were susceptible to accelerated corrosion processes, released
      higher levels of metal ions that correlated to larger decreases in thymidine
      incorporation. Metal ion levels increased with test time for all alloys but were
      not proportional to bulk alloy compositions. Ni ions were released at slightly
      higher than bulk alloy compositions, while Be was released at from four to six
      times that of bulk alloy compositions. The elevated release of Be ions was
      associated with reduced cellular proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560410
TI  - Dental specialists and the IADR.

PMID- 7560411
TI  - Temporomandibular joint sounds.

PMID- 7560412
TI  - Dentin and pulp: endodontics or operative dentistry?

PMID- 7560413
TI  - Dental caries is a transmissible infectious disease: the Keyes and Fitzgerald
      revolution.

PMID- 7560414
TI  - EP-GP and the lipocalin VEGh, two different human salivary 20-kDa proteins.
AB  - Two salivary 20-kDa proteins [the human lipocalin Von Ebner's gland protein
      (VEGh) and extraparotid glycoprotein (EP-GP)] show several remarkable
      similarities and differences. The latter is identical to secretory actin-binding
      protein (SABP), gross cystic disease fluid protein-15 (GCDFP-15), prolactin
      induced protein (PIP), and 17-kDA CD4-binding glycoprotein (gp17). Much is known
      about the distribution, localization, biochemical characteristics, and molecular
      biology of these two proteins, yet there are only few clues about their
      functions.

PMID- 7560415
TI  - Transcription and translation of CSF-1 in the dental follicle.
AB  - The dental follicle, a loose connective tissue sac which surrounds the unerupted
      tooth, is required for eruption to occur. Injection of colony-stimulating factor
      1 (CSF-1) will accelerate molar eruption in rats, as well as stimulate tooth
      eruption in osteopetrotic rats. Utilizing in situ hybridization and reverse-
      transcription polymerase chain-reaction techniques, we show here that CSF-1 mRNA
      is present in vivo in the dental follicle of the first mandibular molar of the
      rat. Analysis of the molars from day 0 through day 10 post-natally demonstrates
      that the maximal expression of CSF-1 mRNA is at day 3 post-natally.
      Immunostaining also reveals that the CSF-1 mRNA is translated, with
      immunostaining for the CSF-1 itself, being heavy in early post-natal days and
      absent by day 9 postnatally. In view of the fact that there is a maximal influx
      of mononuclear cells (monocytes) into the dental follicle at day 3 post-natally-
      an influx which increases the numbers of osteoclasts needed to form a tooth
      eruption pathway--it is probable that the maximal expression of CSF-1 mRNA by day
      3 post-natally contributes to this monocyte influx. Thus, this study establishes
      a relationship among a molecule (CSF-1), cell (monocyte), and tissue (dental
      follicle) that appear to play a major role in tooth eruption.

PMID- 7560416
TI  - Hypertriglyceridemia associated with tumor necrosis factor-alpha in hamster cheek
      pouch carcinogenesis.
AB  - We demonstrated for the first time that 9,10-dimethyl-1,2-benzanthracene (DMBA)
      treated hamsters showed hypertriglyceridemia followed by cachexia.
      Hypertriglyceridemia is believed to be caused in part by the decreased
      lipoprotein lipase (LPL) activity, and by cytokines such as tumor necrosis factor
      (TNF)-alpha. In addition, TNF-alpha action is associated with the LPL activity.
      Therefore, we determined the content of triglyceride (TG), LPL, and TNF-alpha in
      the serum from DMBA-treated hamsters. Elevated TG concentration in the serum of
      tumor-bearing hamsters was more remarkable and preceded the increase in other
      lipids, whereas the activity of LPL, the key enzyme of TG metabolism in vivo, was
      drastically reduced. TNF-alpha, known as an endogenous inhibitor of LPL activity,
      was detected in both the sera and the extract of tumors from DMBA-treated
      hamsters, whereas it was not detectable in any control samples. Pre-incubation of
      control sera with exogenous recombinant human TNF-alpha resulted in a potent
      inhibition of endogenous LPL activity in a dose-dependent manner in vitro.
      Therefore, the presence of TNF-alpha might lead to the increase in plasma TG
      mediated by LPL in tumor-bearing hamsters.

PMID- 7560417
TI  - Biomechanical analysis of jaw-closing movements.
AB  - This study concerns the complex interaction between active muscle forces and
      passive guiding structures during jaw-closing movements. It is generally accepted
      that the ligaments of the joint play a major role in condylar guidance during
      these movements. While these ligaments permit a wide range of motions, it was
      assumed that they are not primarily involved in force transmission in the joints.
      Therefore, it was hypothesized that muscle forces and movement constraints caused
      by the articular surfaces imply a necessary and sufficient condition to generate
      ordinary jaw-closing movements. This hypothesis was tested by biomechanical
      analysis. A dynamic six-degrees-of-freedom mathematical model of the human
      masticatory system has been developed for qualitative analysis of the
      contributions of the different masticatory muscles to jaw-closing movements, it
      was found that the normally observed movement, which includes a swing-slide
      condylar movement along the articular eminence, can be generated by various
      separate pairs of masticatory muscles, among which the different parts of the
      masseter as well as the medial pterygoid muscle appeared to be the most suitable
      to complete this action. The results seem to be in contrast to the general
      opinion that a muscle with a forward-directed force component may not be suitable
      for generating jaw movements in which the condyle moves backward. The results can
      be explained, however, by biomechanical analysis which includes not only muscle
      and joint forces as used in standard textbooks of anatomy, but also the torques
      generated by these forces.

PMID- 7560418
TI  - A follow-up study of radiographic findings in the mandibular condyles of
      orthodontically treated patients and associations with TMD.
AB  - Our earlier studies have shown that some radiographic structural findings in the
      mandibular condyles are more common in orthodontically treated populations than
      in normal populations. To test the hypothesis that these findings are stable, we
      studied condylar findings in panoramic radiographs longitudinally in 39 subjects
      and in 39 sex- and age-matched controls. The subjects had condylar findings at
      the end of orthodontic treatment at about 15 years of age; no such findings were
      seen in the controls. The subjects and controls were re-examined radiographically
      about 12 years after the posttreatment radiographic examination. We also tested
      the hypothesis that radiographic condylar findings are associated with
      temporomandibular disorders (TMD). No statistically significant differences were
      found between subjects and controls in terms of reported subjective TMD symptoms.
      Clinically, the subjects had temporomandibular joint (TMJ) crepitation
      significantly more frequently (27%) than controls (8%) (p < 0.05). Crepitation
      correlated with some reported symptoms and clinical signs, suggesting that
      osteoarthrosis might have been an important etiological factor for TMD in the
      present subjects. At the follow-up examination, radiographic condylar findings
      were seen in 25 subjects and in four controls (p < 0.001). The condylar findings
      varied greatly between the time of orthodontic treatment and follow-up in the
      subjects. The findings had become more severe in 49% of the subjects, more often
      in females than in males (p < 0.05), whereas in 28% of the subjects the condylar
      findings had disappeared. Although the radiographic findings after orthodontic
      treatment fluctuated with age, in most adolescents with changes in their
      condyles, these findings remained constant or became more severe.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7560419
TI  - Self-estimation of oral malodor.
AB  - Bad breath (halitosis, oral malodor) is a common condition, usually the result of
      microbial putrefaction within the oral cavity. Often, people suffering from bad
      breath remain unaware of it, whereas others remain convinced that they suffer
      from foul oral malodor, although there is no evidence for such. The purpose of
      the present investigation was to determine whether objective self-measurement of
      oral malodors is possible. Each of 52 volunteers was asked to sample the odor
      from his/her mouth, tongue, and saliva. Results were compared with (i) self
      assessments prior to (preconception) and following (post-measurement) self
      measurements; (ii) odor judge scores; (iii) dental-measurements (plaque index,
      gingival index, and probing depth); (iv) volatile sulphide levels; (v) salivary
      cadaverine levels; and (vi) intra-oral trypsin-like activity. Among the self
      measurements, only saliva self-scores yielded significant correlations with
      objective parameters. Despite the partial objectivity of saliva self-estimates,
      subsequent post-measurement self-assessments failed to correlate with objective
      parameters. The results suggest that (i) preconceived notions confound the
      ability to score one's own oral malodors in an objective fashion; and (ii)
      partial objectivity can be obtained in the case of saliva self-measurement,
      presumably because the stimulus is removed from the body proper.

PMID- 7560420
TI  - A longitudinal evaluation of fissure sealants applied in dental practices.
AB  - Sealants are highly effective in preventing dental caries in the pits and
      fissures of teeth when applied by trained operators in clinical trials and public
      health programs. The effectiveness of fissure sealants when applied in dental
      practices is still not known. The purpose of this longitudinal study was to
      evaluate the effectiveness of fissure sealants applied in dental practices in
      preventing dental caries on occlusal surfaces of first permanent molars. In 1990,
      on the Island of Montreal, 911 randomly selected children, from 6 to 9 years of
      age, were examined; out of those, 816 and 733 were re-examined in 1991 and 1992,
      respectively. Only the 733 children with complete examination records were
      included in this evaluation. Sealant applications were either personally paid for
      or were paid for by private dental insurers. All children were covered for
      diagnosis and restorative care by a publicly financed and universal insurance
      program. Dental treatment records were provided by Quebec's health insurance
      board. In the epidemiological examination, the occlusal surfaces of first
      permanent molars, which are the only surfaces included in this analysis, were
      classified into: sound, non-cavitated and cavitated status, restored, and sealed.
      Sealants were evaluated for full or partial coverage of the occlusal surface and
      presence of dental caries. During the first and second years, 11.6% and 17.5% of
      the students had new sealants. The number of new sealants placed during the two
      years was 507. Children with caries-free status and whose parents had high school
      education or higher were significantly more likely to receive sealants during the
      study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560421
TI  - Shear vs. tensile bond strength of resin composite bonded to ceramic.
AB  - Since the mode of failure of resin composites bonded to ceramics has frequently
      been reported to be cohesive fracture of either ceramic or resin composite rather
      than separation at the adhesive interface, this study was designed to question
      the validity of shear bond strength tests. The reasons for such a failure mode
      are identified and an alternative tensile bond strength test evaluated. Three
      configurations (A, conventional; B, reversed; and C, all composite) of the
      cylinder-on-disc design were produced for shear bond strength testing. Two
      dimensional finite element stress analysis (FEA) was carried out to determine
      qualitatively the stress distribution for the three configurations. A tensile
      bond strength test was designed and used to evaluate two ceramic repair systems,
      one using hydrofluoric acid (HF) and the other acidulated phosphate fluoride
      (APF). Results from the shear bond strength tests and FEA showed that this
      particular test has as its inherent feature the measurement of the strength of
      the base material rather than the strength of the adhesive interface. In the
      tensile test, failure invariably occurred in the adhesive layer, with HF and APF
      showing a similar ability to improve the bond of resin composite to ceramic. It
      is concluded that the tensile bond strength test is more appropriate for
      evaluating the adhesive capabilities of resin composites to ceramics.

PMID- 7560422
TI  - The effects of cross-linking agents on some properties of HEMA-based resins.
AB  - The use of 2-hydroxyethyl methacrylate (HEMA)-based polymer as a biocompatible
      material has been well-established. HEMA-based resins containing cross-linking
      agents have several potential clinical applications. It is hypothesized that the
      incorporation of cross-linking agent will improve the mechanical properties of
      HEMA-based polymers while reducing water absorption and solubility. The purpose
      of the work reported here was to test this hypothesis and to determine the most
      effective cross-linking agent. A relationship among flexural strength, modulus,
      water absorption and solubility, and concentration of cross-linking agent was
      demonstrated. Strength and modulus tend to increase as the cross-linking agent
      concentration is increased, up to about 50%, after which the values level out or
      begin to fall. Water absorption drops with increasing cross-linking agent over
      the whole range of concentrations. Solubility tends to show a small decrease
      initially (up to 40%), followed by a noticeable increase as cross-linking agent
      concentration is increased. The trends were similar for all cross-linking agents,
      although there were differences in the absolute values in all properties
      depending upon the type of cross-linking agent used.

PMID- 7560423
TI  - Cytotoxic interactive effects of dentin bonding components on mouse fibroblasts.
AB  - Previous studies have shown a wide range of pulpal reactions to dentin bonding
      systems and a poor correlation between in vitro and in vivo toxicity of dentin
      bonding agents. Because dentin bonding agents are composed of multiple components
      which may diffuse through dentin, we hypothesized that these components may cause
      cytotoxicity through interactive (synergistic) effects. We investigated the
      cytotoxicities of four dentin bonding components--HEMA, Bis-GMA, TEGDMA, and UDMA
      -and interactive effects for three binary combinations of the dentin bonding
      components--HEMA and Bis-GMA, Bis-GMA and TEGDMA, and TEGDMA and UDMA.
      Cytotoxicities to Balb/c 3T3 mouse fibroblasts were measured by the MTT assay.
      Concentrations which caused 50% toxicity compared with controls (TC50 values)
      were compared, and the interactive effects were determined by evaluation of the
      differences between observed and expected MTT activities of the cells. The ranks
      of toxicity of the dentin bonding components in terms of TC50 values were as
      follows: Bis-GMA > UDMA > TEGDMA >>> HEMA (least toxic) after 24- and 72-hour
      exposures. As binary combinations, the three combinations of dentin bonding
      components interacted in three ways--synergism, additivism, and antagonism--which
      were influenced by the concentrations of both components. The longer period of
      exposure resulted in a significant increase in the cytotoxicity of the dentin
      bonding components and combinations. The findings indicate that both exposure
      time and the interactions between the dentin bonding components may be important
      parameters in determining the cytotoxicity of dentin bonding agents in vivo.

PMID- 7560424
TI  - Bacterial colonization on titanium, hydroxyapatite, and amalgam surfaces in vivo.
AB  - A study was conducted to evaluate qualitative and quantitative differences in
      bacterial colonization on titanium, hydroxyapatite, and amalgam surfaces in vivo.
      Six healthy adult individuals participated in the study. Two pieces each of
      titanium, hydroxyapatite, and amalgam of similar size were placed in cobalt
      chromium splints and kept intra-orally in each individual for 10 min, and 1, 3,
      6, 24, and 72 hrs. After removal of the splints, the pieces were rinsed in PBS
      and transferred to transport medium. After being vortexed, the samples were
      inoculated on selective and non-selective media for analyses of various
      facultative and anaerobic bacteria. During the experiment, total viable count
      increased on all surfaces. The investigated bacterial groups constituted, on
      average, approximately 60 to 99% of the total viable count on all three types of
      surfaces in each of the experiments, except in the 10-minute samples, when they
      constituted around 20 to 30%. Various streptococcal species predominated and
      usually constituted > 50% of total viable count. Similar colonization patterns of
      Streptococcus spp., Actinomyces naeslundii, Neisseria spp., Hemophilus
      parainfluenzae, Fusobacterium spp., and black-pigmented Prevotella spp. were seen
      at all three types of surfaces. No significant differences among the materials
      regarding colonization of investigated bacteria were found during the study
      period. This study failed to show any qualitative and quantitative differences in
      bacterial colonization among these materials. Titanium, hydroxyapatite, and
      amalgam do not seem to have a marked influence on the early colonization pattern
      in vivo.

PMID- 7560425
TI  - Effect of sucrose monolaurate on acid production, levels of glycolytic
      intermediates, and enzyme activities of Streptococcus mutans NCTC 10449.
AB  - We studied the mechanism by which the antimicrobial compound sucrose monolaurate
      inhibits Streptococcus mutans NCTC 10449 by determining its effect on the rate of
      acid production from glucose and sucrose and the intracellular and extracellular
      levels of glycolytic intermediates. Sucrose monolaurate was more effective than
      either sodium laurate or sodium fluoride in inhibiting acid production at pH 7.0
      from glucose. Inhibition of acid production was the same when either glucose or
      sucrose was the carbon source and in the presence or absence of oxygen.
      Quantitative analysis of various glycolytic intermediates revealed that the steps
      inhibited by sucrose monolaurate were the reactions catalyzed by
      phosphofructokinase and glyceraldehyde 3-phosphate dehydrogenase and/or
      phosphoglycerate kinase. Since the activities of these enzymes in cell-free
      extracts were not decreased by the addition of sucrose monolaurate, the
      inhibition of acid production could not be ascribed to direct effects on the
      enzymes. A decrease in the rate of acid production with corresponding elevations
      in the extracellular levels of glycolytic intermediates indicates that sucrose
      monolaurate inhibits S. mutans by altering the permeability of the cell membrane,
      which causes a loss of important metabolites.

PMID- 7560426
TI  - The effect of fluorhydroxyapatite-derived fluoride on acid production by
      streptococci.
AB  - The effect of fluoride derived from fluorhydroxyapatite (FHAp) minerals on
      bacterial glycolysis under aerobic and strictly anaerobic conditions was studied
      to validate the claims that this mineral could be used as a reservoir of fluoride
      in plaque. To isolate the direct effect of fluoride on bacterial glycolysis from
      that of an indirect pH-buffering effect of hydroxyl or phosphate ions which are
      also dissolved from the mineral, we equalized the pH-fall time course of
      reactions by manually adding KOH or HCl. This ensured that pH effects on
      glycolysis were minimized. Under controlled pH-fall and strictly anaerobic
      conditions, fluoride derived from the dissolution of FHAp containing more than
      30,100 ppm fluoride (i.e., when the substitution of OH by F in the mineral was
      greater than 80%) had a direct inhibitory effect on lactic acid production in
      Streptococcus mutans. Under free pH-fall and strictly anaerobic conditions,
      increasing amounts of fluoride in FHAp (starting as low as 2000 ppm fluoride),
      appeared to have a pronounced indirect inhibitory effect on lactic acid
      production. This was probably mediated through a reducing pH buffer effect of the
      mineral. Even in the presence of high-fluoride FHAp, only 0.01 to 0.025 mmol/L
      fluoride was found in the reaction mixtures, a probable result of non
      stoichiometric dissolution of FHAp. In spite of such low levels of fluoride,
      marked inhibitory effects on bacterial glycolysis were demonstrated. The results
      of this study suggest that high-fluoride FHAp may serve as a reservoir of
      fluoride for the inhibition of anaerobic acid production by S. mutans.

PMID- 7560427
TI  - Curriculum Forum III. Cost and future of Dental Education. Introduction.

PMID- 7560428
TI  - A day in the life of a dean.

PMID- 7560429
TI  - Dream busters ... clinic income.
AB  - In summary, the best clinical education occurs in a setting of exemplary patient
      care. The critical factor is quality--not just technical quality, but those
      features by which patients judge quality. Commitment to service should be
      enhanced and barriers should be minimized in order to achieve efficient and
      personalized patient care. And, schools must always reach for a higher standard,
      (9) exceeding their patients' expectations. As Pacific Bell Telephone says in its
      commercials: "Good enough isn't."

PMID- 7560431
TI  - Dream busters ... student indebtedness.

PMID- 7560432
TI  - The dream busters ... licensure (or, the nightmare before practice).

PMID- 7560430
TI  - Dream busters ... faculty resources.

PMID- 7560433
TI  - Damn the torpedoes--innovations for the future: the new curriculum at the Harvard
      School of Dental Medicine.

PMID- 7560434
TI  - Cost, responsibility, and the future of dental education: summary comments to
      Curriculum Forum III.

PMID- 7560435
TI  - Statistical survey from 1982 to 1991 of 49 patients with malignant melanocytic
      tumors.
AB  - We investigated the clinical characteristics and outcome of 49 patients with
      malignant melanoma: 17 with acral lentiginous melanoma; 14 with nodular melanoma,
      six with superficial spreading melanoma, one with lentigo maligna melanoma, eight
      with melanoma in situ, one with malignant blue nevus, and two with melanoma of
      unknown origin. Of the 41 patients without melanoma in situ, 34.1% were in stage
      I, 17.1% in stage II, and 48.8% in stage III. No patients had reached stage IV.
      All patients with stage I, II, and III melanoma were treated with wide resection,
      lymph node dissection including prophylactic dissection, and combination
      chemotherapy with dacarbazine, nimustine hydrochloride, and vincristine (DAV)
      with or without Interferon-beta. The statistical analysis revealed that tumor
      thickness and level of invasion were factors significantly associated with
      outcome. A gradual increase in the number of new cases of melanoma was seen each
      year of the registration period (1982-1991); there was an approximately 4-fold
      increase during this decade over the previous decade. The majority of the primary
      lesions (80.5%) were located on the upper or lower extremities, the pT4 tumor
      thickness subgroup was the most frequent (39.0% of all melanomas), and invasion
      level IV was the most common (42.5%). About half (51.2%) of the melanoma patients
      were stage I or II; this group had a 5-year survival rate of 100%. The stage III
      patients had a 5-year survival rate of only 54.2% (p < 0.05).

PMID- 7560436
TI  - Correlation of lesional skin corneometry values with serum E-selectin levels and
      disease severity in patients affected by plaque-type psoriasis: recovery after
      effective therapy.
AB  - Ten subjects with plaque-type psoriasis (5 females, 5 males, median age 47, range
      20-71 years, median psoriasis area and severity index [PASI] score = 15.5, range
      8.1-23.0) were observed before (week 0) and at the second and sixth week after
      starting treatment (PASI = 10.5, range 7.8-14.6; PASI = 8.5, range 1.6-11.6,
      respectively). At each of these times, the patients were evaluated for both
      lesional and unlesional skin corneometry and serum E-selectin values, previously
      shown to be increased in psoriatic subjects. At time 0, both the corneometry and
      the E-selectin values were significantly correlated with the PASI, infiltration
      and desquamation scores. As expected, the corneometry was statistically higher in
      the unlesional than in the lesional areas (p < 0.001). After therapy, the lesion
      improvement was related both to the PASI scores and E-selectin level decreases
      (from median levels of 15.5 to 8.5 and from 18 to 13.2 ng/ml, respectively, p <
      0.05) as well as to the corneometric level increases (from a median value of 34.5
      to 42, p < 0.05). Considering the data obtained at all of these times,
      significant correlations were found between the PASI scores, lesional skin
      corneometry and serum E-selectin levels. In conclusion, lesional corneometry
      seems to represent an objective alternative method for reliably monitoring
      psoriatic patients.

PMID- 7560437
TI  - Human type VI collagen: purification from human subcutaneous fat tissue and an
      immunohistochemical study of morphea and systemic sclerosis.
AB  - Collagen was isolated from human placenta by pepsin digestion and salt
      precipitation. This collagen was similar in its electrophoretic mobility and
      immunological reactivity with monoclonal antibody to form B of type VI collagen
      in the literature (Trueb B, Schreier T, Bruckner P and Winterhalter K. 1987. Eur.
      J. Biochem. 166: 699-703). We prepared polyclonal rabbit antiserum against alpha
      2 chain of type VI collagen and performed an immunohistochemical study using this
      polyclonal antibody. It reacted in fat tissue and around vessels and peripheral
      nerves in normal human skin. To confirm the presence of type VI collagen in fat
      tissue, we isolated collagen from human subcutaneous tissue. This collagen showed
      a similar pattern in polyacrylamide gel electrophoresis with that from human
      placenta and cross-reacted with monoclonal or polyclonal antibody against type VI
      collagen. By immunohistochemical staining, abundant type VI collagen was observed
      in the septum of subcutaneous fat tissue in morphea or systemic sclerosis. In the
      mild hyalinizing areas or after treatment with 6M urea or hyaluronidase in highly
      hyalinized areas, the staining of type VI collagen increased. These data suggest
      that the amount of type VI collagen in subcutaneous tissue is involved in the
      early phases of these fibrosing disorders and that type VI collagen accumulates
      even more in hyalinizing tissue in late phases of these diseases.

PMID- 7560438
TI  - Clinico-epidemiological profile of ichthyosis in south Indian patients.
AB  - A high frequency rate of hereditary ichthyosis (141.89 per 1000) was detected in
      a 1029 member South Indian study population selected at random from the skin
      outpatients of a teaching hospital. An age and sex matched control population
      screened from the medical and pediatric outpatients of the same institute
      recorded the incidence of ichthyosis vulgaris as 150 per 1000 population which is
      even higher.

PMID- 7560439
TI  - Tripe palms: a cutaneous marker of internal malignancy.
AB  - Tripe palms is a distinctive paraneoplastic cutaneous sign which is frequently
      associated with internal malignancy, specially carcinomas of the lung and
      stomach. We describe a patient with ovary carcinoma who showed a curious rugose
      thickening of the palms with accentuation of the normal dermatoglyphic ridges.
      The lesions were a specially prominent on the fingertips. The patient also showed
      classical acanthosis nigricans in the axillae and groin. The soles were spared.
      Histopathologic findings in palmar lesions consisted of an undulant epidermis,
      with hyperkeratosis, acanthosis, and papillomatosis. Excision of the ovary
      carcinoma was followed by complete regression of the cutaneous lesions. We review
      the literature about tripe palms and discuss the relationship between this
      striking cutaneous manifestation and internal malignancy.

PMID- 7560440
TI  - Graft versus host disease with mixed chimerism.
AB  - We report a patient with graft versus host disease (GVHD) with mixed chimerism
      (MC). The patient had chronic myelogenous leukemia and received bone marrow
      transplantation (BMT) from his elder sister. Eighty days after BMT, erythematous
      lesions appeared on his chest. Histological examination from the skin lesion
      revealed lymphocytic infiltration into the upper dermis. Eosinophilic necrotic
      keratinocytes were scattered through the epidermis. Liquefaction degeneration was
      also recognized. Sicca syndrome appeared from 110 days after BMT. Detection of
      host origin Y-chromosome-specific DNA by polymerase chain reaction (PCR) method
      in bone marrow and peripheral blood showed that all bone marrow samples obtained
      6 months from BMT were positive for Y-specific DNA, while peripheral blood became
      positive in the 60th month after BMT. The host origin normal karyotype (46,XY) in
      the bone marrow samples was identified for the first time in the 60th month after
      BMT. These results indicate that host-origin hematopoietic cells survived after
      BMT.

PMID- 7560441
TI  - "Malignant Spitz nevus" in a 2-year-old Japanese child.
AB  - Smith et al. (1989) have reported a variant of Spitz's nevus with histological
      atypical features. Despite local lymph node metastases, further metastases were
      not observed. They proposed the name "malignant Spitz nevus" for this variant. A
      2-year-old Japanese girl had a large nodule (27 x 17 mm) surrounded by an
      indurated erythema over the Achilles tendon. Histologically, it proved to be a
      melanocytic lesion resembling spindle cell and epithelioid cell nevus (Spitz's
      nevus) with unusual features; the tumor extended deep into the subcutis, and the
      mitotic figures deep into the tumor, together with prominent lymphatic vessel
      invasion by melanocytes. Thus the tumor was aptly termed "malignant Spitz nevus".
      Flow cytometric analysis of the DNA content revealed a diploid pattern. The child
      is well 5 years after a wide resection of the tumor. The diploid pattern of the
      DNA content as well as the good prognosis could support the idea that "malignant
      Spitz nevus" fits within the spectrum of Spitz's nevus.

PMID- 7560442
TI  - Striated muscle hamartoma of the nostril.
AB  - We observed two females, an 11-month old and a 15-year-old, each with a round,
      soft mass in the nostril. Histologically, numerous bundles of striated muscle
      fibers were seen in the masses among normal dermal components. The lesions were
      excised without complications. Four patients with similar lesions confirmed
      clinically and histologically have been reported in the literature under various
      diagnostic names. These masses were diagnosed as striated muscle hamartomas in
      view of their characteristic features: congenital round, soft masses on the
      midline of the head or neck with multiple, mature striated muscles observed in
      the mass. Since these lesions may be associated with such anomalies as amniotic
      band syndrome and lipoma of the brain, a complete medical examination is required
      of such patients.

PMID- 7560443
TI  - Scleroderma-like changes in a patient with insulin-dependent diabetes mellitus.
AB  - A 38-year-old Japanese woman with diabetes showed sclerosis of the hands, a short
      sublingual frenulum, and hypomotility of the esophagus. She had been on insulin
      therapy for insulin-dependent diabetes mellitus since the age of 15. For the
      previous one year, the proximal interphalangeal joints had become painful and
      swollen with sclerosis of the hands. Although these findings are also seen in
      PSS, this case was assumed to be due to diabetes mellitus. The patient had a high
      serum level of HbA1c, which may reflect a poor control of diabetes and non
      enzymatic glycosylation of collagen fibers, resulting in an accumulation of
      collagen in the dermis.

PMID- 7560444
TI  - Successful treatment of severe arthralgia associated with palmoplantar pustulosis
      with low-dose oral cyclosporine A.
AB  - Two patients with severe arthralgia associated with palmoplantar pustulosis (PPP)
      were treated with oral cyclosporine A (CsA). Clinical efficacy was assessed on a
      0-4 point scale for erythema, desquamation, infiltration, and pustulation, and on
      a 0-3 point pain scale. Skin lesions and arthralgia improved within twelve weeks
      with low dose CsA ranging from 2.1 to 2.2 mg/kg/day. High levels of plasma
      interleukin-6 (IL-6) were reduced to the normal range.

PMID- 7560445
TI  - Pyoderma gangrenosum with systemic involvement.
AB  - We report a case of a patient with pyoderma gangrenosum associated with
      multisystemic manifestations. The patient showed liver dysfunction, respiratory
      failure, and aseptic meningeal reaction. Corticosteroid therapy was efficient in
      treating both the skin lesions and the other systemic disorders.

PMID- 7560446
TI  - Multiple lentigines (Leopard) syndrome with Chiara I malformation.
AB  - This is a case report of multiple lentigines (Leopard Syndrome) with Chiari
      malformation, i.e. a herniation of the cerebellum into the foramen magnum. This
      male patient had generalized multiple lentigines since birth, and the lesions
      spread steadily, involving the scalp but sparing all mucous membranes. Organ
      system involvements included heart murmur, ocular hypertelorism, and retardation
      of growth.

PMID- 7560448
TI  - Balloon cell melanoma cells in metastatic lesions from pedunculated malignant
      melanoma.

PMID- 7560447
TI  - Infrequent expression of protein p53 in epidermotropic variants of cutaneous T
      cell lymphoma.
AB  - Although diverse types of lymphomas have been examined for immunohistochemical
      detection of p53 protein, little information is available with regard to p53
      protein expression in CTCL. We analyzed cutaneous biopsy specimens of 22 patients
      with the diagnoses of mycosis fungoides or Sezary syndrome with polyclonal rabbit
      anti-p53 antiserum CM-1. Staining of neoplastic cells was observed only in two
      patients with advanced disease. Overexpression of p53 protein does not seem to be
      a major feature of either mycosis fungoides or Sezary syndrome.

PMID- 7560449
TI  - Androgen status in adolescent women with acne vulgaris.
AB  - Androgens are essential for the development of acne. The object of this study was
      to elucidate the androgen status of women with adolescent (Tanner's stage IV-V)
      acne alone and compare them to age-matched normal controls. We measured serum
      levels of total testosterone (T), free testosterone (FT), dihydrotestosterone
      (DHT), and dehydroepiandrosterone sulfate (DHEA-S) in 15 women with adolescent
      acne and 13 age-matched healthy controls. No significant differences were found
      between the mean levels of T, FT or DHT levels in patients and controls. However,
      the mean levels of DHEA-S in the patient population (1886 +/- 829 ng/ml) were
      significantly (p < 0.05) higher than normal controls (1287 +/- 620 ng/ml). There
      was also no correlation between androgen levels and acne severity. Thus it is
      unlikely that serum androgens play a principal role in women with adolescent
      acne.

PMID- 7560450
TI  - Is micropigmentation surgery an answer to stable bindi-induced depigmentation?

PMID- 7560451
TI  - Differential cell- and immuno-biological properties of murine B16-F1 and F10
      melanomas: oncogene c-fos expression, sensitivity to LAK cells and/or IL-2, and
      components of gangliosides.
AB  - Differential cell- and immuno-biological properties of two murine melanoma B16
      variants, B16-F1 and F10, were investigated. Studies focused on the expression of
      proto-oncogene c-fos, sensitivities to LAK cells and/or IL-2, and modulation of
      the expression of ganglioside components after treatment with IL-2. Proto
      oncogene c-fos was found to be highly expressed in F10 lines by an in situ
      hybridization technique and also in F10 lung metastatic nests by
      immunofluorescent staining with anti-c-fos antibody. F1 melanomas were more
      sensitive to local injection of IL-2. F10 melanomas hardly responded to IL-2
      treatment, but successive injections of a combination of LAK cells and IL-2 did
      cause prolongation of survival rates, even of F10 melanoma-burdened mice. A major
      component of gangliosides of both F1 and F10 melanomas was GM3. Production of GM3
      in F10 melanomas treated with IL-2 for 4 days increased, and, if the treatment
      was continued for 7 days, minor components of gangliosides, such as GM2, GM1, and
      GD1a, appeared only in F1 melanomas, while the increase of production of GM3
      disappeared in both melanomas. These experimental results may provide clues for
      additional mechanisms which allow these two murine melanoma variants to show
      different implantation and metastasis rates.

PMID- 7560452
TI  - Serial cultivation of human nail matrix cells under serum-free conditions.
AB  - We have established serial cultures of human nail matrix cells (NMCs) under serum
      free conditions. We cultured NMCs using two different methods depending upon the
      volume of nail matrix obtained. When a sufficient amount of nail matrix was
      obtained, they were minced and treated with 0.25% trypsin and 0.03% EDTA. The
      NMCs were transferred directly as a dispersed cell culture into KGM medium.
      Because a sufficient amount of matrix was rarely obtained, we developed a method
      by which NMCs were cultured primarily as implanted small matrices in Eagle's MEM
      (high Ca+ medium) supplemented with 15% fetal bovine serum for the first 4 to 5
      days; during this time, the NMCs expanded from the matrices and formed colonies
      around them. NMCs then were cultured with KGM. In both methods, KGM medium
      supported the growth of NMCs without a biological feeder layer. These cells could
      be cultivated serially for at least seven passages. Half of the cells were
      positively stained with a monoclonal antibody against hair (hard) keratin which
      is expressed in nail matrix in vivo, indicating that the cells originated from
      the nail matrix. These methods will now permit investigations of nail matrix
      cells that previously were unfeasible because of the relative lack of cells and
      difficulties with propagation.

PMID- 7560453
TI  - Successful treatment of dark-colored epidermal nevus with ruby laser.
AB  - The pulsed ruby laser has a selective thermolytic effect. Recently, it has been
      available for the treatment of superficial pigmented disorders. We studied 5
      cases of epidermal nevus treated with the pulsed ruby laser. In comparison with
      the usual methods including electrocautery, cryotherapy and skin abrasion, ruby
      laser therapy is an excellent tool due to technological ease and rapid
      improvement. Depigmentation after treatment in 2 cases was the only side effect
      of this therapy. Bose cases had a dark pigmentation of the skin. Despite of the
      risk of discoloration, the ruby laser is one of the most effective tools for
      therapy of pigmented epidermal nevus.

PMID- 7560454
TI  - Immunofluorescence study of pemphigus from north India.
AB  - Both serum studies by indirect immunofluorescence (IIF) tests and skin biopsy
      examination by direct immunofluorescence (DIF) were performed on 22 cases of
      pemphigus with clinically active lesions. Twenty cases had pemphigus vulgaris and
      two, pemphigus foliaceus. The majority of cases (70%) were between 21 and 60
      years old; the mean age was 39.5 +/- 12.7 years. There was no sex predilection.
      DIF showed the positive fluorescence of intercellular cement substance (ICS) of
      the epidermis in all 22 cases (100%). IgG was positive in 77.2%, followed
      sequentially by C3C (50%), IgA (45.45%), and IgM (36.36%). Six cases (27.27%)
      also showed granular immunoglobulin and/or complement deposits at the
      dermoepidermal junction. IIF detected serum antiepithelial antibodies in 18 cases
      (81.81%) using human esophagus as substrate. Most of these cases (88.88%) showed
      IgG type of antibodies; the other 11.11% exhibited IgA and IgM in low
      concentrations. 1+ titer positivity was observed in 15 cases. This study
      demonstrates the value of DIF for a definitive diagnosis of pemphigus. However,
      it is also important to appreciate that immunofluorescence is not a substitute
      for histopathology, but rather complementary to it.

PMID- 7560455
TI  - A case of bullous pemphigoid with antibodies against intercellular 130 kd
      antigen.
AB  - Pemphigus and bullous pemphigoid are two typical autoimmune bullous diseases that
      involve circulating autoantibodies directed against the epidermal cell surface
      and the epidermal basement membrane zone, respectively. The coexistence of
      pemphigus and bullous pemphigoid is rare. We describe a case of a 79-year-old man
      who had tense bullae and erythematous, erosive lesions on his trunk and four
      extremities. Histopathology revealed subepidermal blister formation without any
      evidence of intraepidermal acantholytic changes. Direct immunofluorescence study
      demonstrated deposition of IgG on the epidermal intercellular spaces, as well as
      along the basement membrane zone; C3 was detected only on the latter. Indirect
      immunofluorescence study using monkey esophagus as a substrate demonstrated the
      presence of circulating antibodies against both junctional and intercellular
      antigens. In order to analyze the precise nature of this patient's antibodies,
      indirect immunofluorescence study using cultured human keratinocytes and
      immunoblot analyses were performed. Pemphigus vulgaris sera showed smooth and
      uniform staining on intercellular spaces. The patient's serum showed a granular
      and uneven staining pattern. Immunoblot analysis showed that the patient's serum
      reacted with the typical 230 kd (bullous pemphigoid) antigen and 130 kd antigen,
      which is close to the pemphigus vulgaris antigen.

PMID- 7560456
TI  - Bilateral inguinal scrofuloderma during steroid therapy in a patient with bullous
      pemphigoid.
AB  - This report described a case of scrofuloderma that developed in the bilateral
      inguinal regions during treatment of bullous pemphigoid with systemic
      corticosteroid. Analysis of the literature on scrofuloderma between 1978-1993
      disclosed that the number of cases with extracervical involvement are increasing.
      Immunosuppression could disseminate tuberculous focuses, resulting in
      extracervical involvement of SD connected with the underlying extrapulmonary
      tuberculous lesions.

PMID- 7560457
TI  - Erythema gyratum repens unassociated with underlying malignancy.
AB  - A case of erythema gyratum repens occurring in a 62-year-old woman is presented
      together with a review of the literature. Evaluation and follow-up for the
      development of malignancy over a 32-month period failed to reveal any evidence of
      malignancy. Formerly, all cases of erythema gyratum repens were evaluated in
      terms of an association with an underlying malignant disorder. To date, only
      sixty cases have been reported in the literature; 14 (23%) were not found to be
      associated with any neoplasm. Therefore, this term is now also used for cases
      unassociated with malignancy. Erythema gyratum repens is a cutaneous eruption
      with a characteristic diagnostic morphology resembling a wood grain pattern.

PMID- 7560458
TI  - A case of lichen myxedematosus with clearly exacerbated skin eruptions after UVB
      irradiation.
AB  - We report a 48-year-old male with typical lichen myxedematosus, liver
      dysfunction, and diabetes mellitus. His skin eruptions were clearly exacerbated
      after accidental over-irradiation by UVB. These findings were clinically and
      histologically confirmed. The pathogenesis is still unknown, but we consider it
      to be due to Koebner phenomenon.

PMID- 7560459
TI  - An autopsy case of malignant lymphoma with Lyell's syndrome.
AB  - We present a case of fatal Lyell's syndrome which developed following a CT
      examination using omnipaque 3000 contrast medium. A 59-year-old man was suffering
      from malignant lymphoma. He was readmitted to this hospital due to relapse of
      fever and lymph node swelling. On the day of readmission, generalized erythema,
      purpura, and mucosal erosions developed after a CT examination. Steroids and
      chemotherapy were ineffective, and he expired approximately two weeks after
      admission. Drug-induced dermatopathy or leukemic cell infiltration in the skin
      was clinically suspected. Histological findings disclosed toxic epidermal
      necrolysis.

PMID- 7560460
TI  - Erythematous papules in a patient with cardiac myxoma: a case report and review
      of the literature.
AB  - A 35-year-old woman was followed up by a physician for one and a half years as a
      case of transient ischemic attach (TIA) due to thrombosis. She had a few
      erythematous papules on the dorsal side of her right forearm and on the right
      side of her neck. From the history of TIA and the transient erythematous papules,
      we suggested the possibility of cardiac myxoma. Echocardiogram demonstrated a
      large mass in her left atrium. An immediate operation was carried out, and the
      cardiac myxoma was excised surgically. Histological examination of the
      erythematous papule revealed myxoma emboli.

PMID- 7560461
TI  - Odontotrichodysplasia: a case report with a review of conditions combining
      ectodermal dysplasia (subgroup 1-2) with skin manifestations.
AB  - We report a 5-year-old girl with partial anodontia, hypotrichosis,
      hyperpigmentation of the skin, absence of pilosebaceous structures, and long thin
      fingers. There has as yet been, to the best of our knowledge, no report of such a
      combination of features. A review of conditions combining ectodermal dysplasia
      (subgroup 1-2) with skin manifestations is presented.

PMID- 7560462
TI  - Primary cutaneous meningioma on the scalp: report of two siblings.
AB  - Primary cutaneous meningioma (PCM) is a rare tumor whose pathogenesis is quite
      obscure. We reported PCMs occurring on almost the same occipital region of two
      siblings studied by histology, immunohistochemistry, and electron microscopy.
      Both lesions were attached to duras, but extracranial. One lesion was
      histologically diagnosed as meningothelial meningioma; its tumor cells showed
      electron microscopically interdigitating cytoplasmic processes with junctional
      complexes. The other was interpreted as fibroblastic meningioma; its tumor cells
      were arranged linearly in a stepping-stone arrangement and had small dense bodies
      in the cytoplasm. The tumor cells stained positively with anti-vimentin antibody.
      Both lesions had adenomatous hyperplasia of the eccrine glands. Although the
      histologic and electron microscopic features of these two lesions slightly
      differed from each other, their pathogenesis was essentially considered to be
      acoelic or rudimentary meningocele.

PMID- 7560463
TI  - Amelanotic bone marrow infiltration secondary to pigmented malignant melanoma.

PMID- 7560464
TI  - Alopecia universalis in a patient with psoriasis vulgaris.

PMID- 7560465
TI  - Mild reduction of generalized rash in guinea pigs experimentally infected with
      varicella zoster virus or herpes simplex virus type 1.

PMID- 7560466
TI  - Intensive care medicine--a European journal.

PMID- 7560467
TI  - Reduction of ventilator settings allowed by intravenous oxygenator (IVOX) in ARDS
      patients.
AB  - OBJECTIVE: To evaluate the possibility of reducing ventilator settings to "safe"
      levels by extrapulmonary gas exchange with IVOX in ARDS patients. DESIGN:
      Uncontrolled open clinical study. SETTING: Medical Intensive Care Unit of a
      University Hospital. PATIENTS: 6 patients with ARDS who entered into IVOX phase
      II clinical trials. INTERVENTIONS: The end-point of this study was to reduce
      ventilator settings from the initial values, recorded on the day of inclusion, to
      the following: peak inspiratory pressure < 40 cmH2O, mean airway pressure < 25
      cmH2O and tidal volume < 10 ml/kg. Trials to achieve this goal were made on
      volume-controlled ventilation within the 24 h before and after IVOX insertion.
      Comparison of the results achieved during these trials used Wilcoxon test.
      RESULTS: Before IVOX implantation reduction of ventilator settings was not
      possible in the 6 patients, despite a non-significant increase in PaO2/FIO2 was
      achieved. IVOX permitted significant decrease in PaCO2 (from 60.5 +/- 15 to 52 +/
      11 mmHg; p = 0.02) before any modification of the ventilatory mode. After IVOX
      insertion, a significant decrease of the ventilator settings was performed: peak
      and mean airway pressures dropped from 44 +/- 10 to 36.8 +/- 6.7; p = 0.02 and
      from 26.3 +/- 5.6 to 22.5 +/- 3.9 cmH2O; p = 0.02, respectively. Concommitantly,
      PaCO2 remained unchanged and PaO2/FIO2 increased significantly from 93 +/- 28 to
      117 +/- 52; p = 0.04. The interruption of oxygen flow on IVOX was associated with
      a slight decrease of the oxygen variables. Tolerance of IVOX was satisfactory.
      However, a significant decrease both in cardiac index and in pulmonary wedge
      pressures (from 4.5 +/- 1.2 to 3.4 +/- 9; p = 0.03 and from 16 +/- 5 to 11 +/- 2;
      p = 0.04, respectively) was observed. CONCLUSION: Gas exchange achieved by IVOX
      allowed reduction of ventilator settings in 6 ARDS patients in whom previous
      attempts have failed. CO2 removal by the device, may explain these results.
      Efficacy of IVOX on arterial oxygenation was uncertain.

PMID- 7560468
TI  - A controlled trial of nebulized salbutamol and adrenaline in acute severe asthma.
AB  - OBJECTIVE: To compare efficacy and safety of nebulisation of adrenaline (2 mg
      over 10 min) and salbutamol (5 mg over 10 min) in acute severe asthma. DESIGN:
      Prospective randomized and double blind study. SETTING: Intensive care unit of a
      University teaching hospital. PATIENTS AND PARTICIPANTS: 22 asthmatic patients
      presenting to the emergency room with acute severe asthma. INTERVENTIONS:
      Patients were randomly assigned to receive either adrenaline (n = 11) or
      salbutamol (n = 11) via a nebulizer. Additional treatment comprised
      hydrocortisone hemisuccinate (100 mg) and supplemental oxygen (71/min). The
      efficacy and safety of both drugs were evaluated at 20 and 40 min. RESULTS: A
      statistically significant increase in the Peak Expiratory Flow (PEF) was achieved
      at the 20th min in both groups (from 85 +/- 38 l/min to 120 +/- 45 l/min; p <
      0.001; and from 107 +/- 28 l/min to 145 +/- 19 l/min; p < 0.001; in adrenaline
      group and salbutamol group respectively). With both drugs, PEF further increased
      at 40 min to a level that was statistically significant when compared to the 20
      min evaluation. The magnitude of the absolute variation in PEF was similar with
      both drugs. Both drugs induced a significant decrease in heart rate, respiratory
      frequency and PaCO2 while the increase of PaO2/FIO2 ratio was not significant.
      The decrease of respiratory frequency at 40 min was more important with
      salbutamol (p = 0.03). No side effects were recorded in both groups. CONCLUSION:
      After a single dose, nebulized adrenaline (2 mg) proved as effective and safe as
      salbutamol (5 mg) in acute severe asthma.

PMID- 7560469
TI  - A five-year study of severe community-acquired pneumonia with emphasis on
      prognosis in patients admitted to an intensive care unit.
AB  - OBJECTIVES: To characterize the epidemiology and to determine the prognosis
      factors in severe community-acquired pneumonia among patients admitted to an
      intensive care unit. DESIGN: Retrospective clinical study. SETTING: Intensive
      Care and Infectious Diseases Unit of a municipal general hospital of Lille
      University Medical School. PATIENTS: 299 consecutive patients exhibiting severe
      community-acquired pneumonia. MEASUREMENTS AND RESULTS: On admission to ICU, 149
      patients required mechanical ventilation for acute respiratory failure and 44
      exhibited septic shock. Pulmonary involvement was bilateral in 71 patients. There
      were 260 organisms isolated from 197 patients (65.9%), the most frequent being
      Streptococcus pneumoniae (n = 80), Staphylococcus spp. (n = 57) and Gram-negative
      bacilli (n = 81). Overall mortality was 28.5% (85 patients). According to
      univariate analysis, mortality was associated with age over 60 years, anticipated
      death within 5 years, immunosuppression, shock, mechanical ventilation, bilateral
      pulmonary involvement, bacteremia, neutrophil count < 3500/mm3, total serum
      protein level < 45 g/l, serum creatinine > 15 mg/l, non-aspiration pneumonia,
      ineffective initial therapy and complications. Multivariate analysis selected
      only 5 factors significantly associated with prognosis: anticipated death within
      5 years, shock, bacteremia, non-pneumonia-related complications and ineffective
      initial therapy. CONCLUSION: The effectiveness of the initial therapy appears to
      be the most significant prognosis factor and, as the one and only related to the
      initial medical intervention, suggests a need for permanent optimization of our
      antimicrobial strategies.

PMID- 7560470
TI  - Clinical investigation in intensive care. One step forward, two steps back.

PMID- 7560471
TI  - The predictive value of four scoring systems in liver transplant recipients.
AB  - OBJECTIVE: To compare 4 general severity classification scoring systems
      concerning prognosis of outcome in 123 liver transplant recipients. The compared
      scoring systems were: the mortality prediction model (admission model and 24 h
      model); the simplified acute physiology score; the acute physiology and chronic
      health evaluation (Apache II) and the acute organ systems failure score. DESIGN:
      Retrospective, consecutive sample. SETTING: Adult intensive care unit in a
      university hospital. PATIENTS: 123 adult liver allograft recipients after
      admission to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The scoring
      systems were calculated as described by the authors to classify the severity of
      illness after admission of the allograft recipients to the intensive care unit.
      The mean and median values of survivors and the group of patients, that died
      during hospital stay were compared. Receiver-operating characteristics were
      plotted for all scoring systems and the areas under the curves of receiver
      operating characteristics were calculated. The predictive value of the 4 scoring
      systems was tested using a variety of sensitivity analyses. The mortality
      prediction model (24 h model) was found to have a high significance (p < 0.001)
      in predicting mortality and showed the greatest area under the curve (0.829).
      Simplified acute physiology score (p < 0.001) and acute physiology and chronic
      health evaluation (Apache II) (p < 0.01) had a high significance as well, but did
      not hit the level of prognosis of mortality prediction model, as shown in the
      area under the curves. Accordingly, sensitivity was highest in MPM-24 h (83%),
      followed by SAPS (72%) and Apache II (71%). MPM-24 h had a total
      misclassification rate of 22% (SAPS = 32%, Apache II = 33%). MPM-admission failed
      in predicting mortality (sensitivity = 52%). Organ systems failure score seemed
      not to be useful in liver transplant recipients. CONCLUSION: General disease
      classification systems, such as the mortality prediction model, simplified acute
      physiology score or acute physiology and chronic health evaluation are good
      mortality prediction models in patients after liver transplantation. We suggest
      that there is no need for improvement of a special scoring system.

PMID- 7560473
TI  - Further prospective evidence of a circadian variation in the frequency of call
      for sudden cardiac death. Belgian Cardiopulmonary Cerebral Resuscitation Study
      Group.
AB  - OBJECTIVE: To determine whether in a larger data base call for sudden cardiac
      death exhibits a specific circadian rhythm similar to that recently demonstrated
      by Levine et al. DESIGN AND SETTING: The time of the day of calls received for
      out-of-hospital cardiac arrests (OOHCA) prospectively registered between 1983 and
      '90 by 7 major Belgian pre-hospital EMS-MICU services. Chrono-biologic assessment
      was made by two-harmonic linear regression analysis of the data tabulated by hour
      of the day. The hourly distribution of calls for OOHCAs was subjected to Fourier
      transformation resulting in a periodogram. PATIENTS: 3471 OOHCAs with presumed
      cardiac etiology and age of more than 18 years versus 2007 inpatients registered
      in the same period. MEASUREMENTS AND RESULTS: Significant and remarkably similar
      circadian patterns were found (R-square = 0.84) for the cardiac origin OOHCAs and
      the ventricular fibrillation OOHCAs. There is a low incidence during the night
      and an increased incidence from 6 a.m. until noon with an additional early
      afternoon-peak. The data were always better fitted when applying sinusoids with
      periods of 8 and 24 h instead of 12 and 24 h. Our observed circadian distribution
      resembles the reported circadian variation of ischaemic episodes, ventricular
      tachycardia and acute myocardial infarction in the awake hours. The time
      distribution of OOHCA (cardiac origin) differs significantly from OOHCA (non
      cardiac origin) and from in-hospital cardiac arrests. The in-hospital CA pattern
      shows less deviation. The age dependent variation in the incidence of cardiac
      origin OOHCAs, was not obvious for the ventricular fibrillation subgroup.
      CONCLUSION: Knowledge about the cyclical nature of incidence of cardiac arrests
      is useful to improve intersystem comparisons and make sound decisions about
      prophylaxis, treatment and allocation of resources.

PMID- 7560472
TI  - Effect of extracorporeal life support on cerebral blood flow, metabolism and
      electrophysiology in normothermic cats.
AB  - OBJECTIVE: Recently, extracorporeal life support (ECLS) by venoarterial bypass
      perfusion has been recommended for the treatment of refractory respiratory and/or
      cardiac failure but the safety of this application for the brain is not yet
      established. Therefore, the effects of normothermic ECLS on cerebral blood flow,
      metabolism and electrophysiology were studied in cats with total arrest of
      cardiopulmonary circulation. DESIGN: An extracorporeal circulation (ECC) system,
      consisting of a roller pump, a membrane oxygenator and a heat exchanger, was
      connected to the circulation of cat by cannulae inserted via the jugular vein and
      femoral vessels. After 2 h ECLS brains were frozen in situ and investigated for
      changes in regional metabolism. MEASUREMENTS AND RESULTS: During 2 h ECC
      hematocrit declined from 37 +/- 7% to 21 +/- 10% (means +/- SD, p < 0.05),
      cerebral blood flow decreased to 73 +/- 14% of control (p < 0.05) and cerebral
      oxygen delivery to 46 +/- 13% of control (p < 0.05) although arterial blood
      pressure and bypass flow rate did not change. Plasma lactate increased from 0.8
      +/- 0.3 to 9.2 +/- 4.2 mumol/ml (p < 0.05), and brain tissue lactate from 2.3 +/-
      0.9 to 10.6 +/- 2.7 mumol/g (p < 0.05). Hematocrit correlated positively with
      cerebral oxygen delivery (r = 0.86, p < 0.001). CONCLUSIONS: These data
      demonstrate that ECLS is associated with reduced cerebral oxygen delivery and may
      cause brain hypoxia despite normal blood pressure. This complication may
      contribute to the high incidence of neurological disturbances after prolonged
      ECLS.

PMID- 7560474
TI  - Are the effects of noradrenaline, adrenaline and dopamine infusions on VO2 and
      metabolism transient?
AB  - OBJECTIVE: To determine whether noradrenaline, adrenaline and dopamine have
      persistent actions on VO2 and metabolism. DESIGN: Descriptive laboratory
      investigation. SETTING: Laboratory of the Department of Anaesthesiology at a
      University Hospital. SUBJECTS: 9 volunteers. INTERVENTION: VO2 and the plasma
      concentration of glucose and free fatty acids were measured prior to and during a
      4 h infusion of saline (control), noradrenaline (0.14 microgram/kg min)
      adrenaline (0.08 microgram/kg min) or dopamine (7 micrograms/kg min), n = 9 each.
      VO2 was measured using an open circuit gas exchange system. MEASUREMENTS AND MAIN
      RESULTS: VO2 increased from 250 +/- 22 ml/min to 280 +/- 38 ml/min during
      noradrenaline, to 298 +/- 30 ml/min during adrenaline and to 292 +/- 39 ml/min
      during dopamine infusion. The plasma glucose concentration increased from 6.2 +/-
      0.6 mmol/l to 8.8 +/- 0.8 mmol/l, 13.2 +/- 1.4 and 7.3 +/- 0.4 mmol/l during
      infusion of noradrenaline, adrenaline or dopamine, respectively. The plasma free
      fatty acid concentration increased from 0.28 +/- 0.10 mmol/l to 0.79 +/- 0.21
      mmol/l during noradrenaline and to 0.52 +/- 0.09 mmol/l during dopamine. In
      contrast, free fatty acid values averaged baseline values at the end of the
      adrenaline infusion after an initial increase to 0.72 +/- 0.31 mmol/l.
      CONCLUSIONS: Administration of noradrenaline, adrenaline or dopamine resulted in
      persistent increases in VO2 in volunteers. With the exception of the transient
      adrenaline effect on fatty acids the metabolic actions were steady during 4 h of
      adrenergic stimulation. Since the adrenergic effect on VO2 is persistent over
      time a similar action in patients (e.g. septic shock) during treatment with
      adrenoceptor agonists may be important. Thus, an increase in VO2 during therapy
      may not only reflect an oxygen debt but also a pharmacodynamic action of
      adrenoceptor mediated calorigenic and metabolic induction.

PMID- 7560475
TI  - Adrenocortical function during septic shock.
AB  - OBJECTIVE: To investigate, in patients with severe septic shock, the
      adrenocortical function assessed by daily plasma cortisol determinations during
      the first 72 h and by the short synthetic ACTH stimulation test performed within
      24 h of the onset of shock. DESIGN: Prospective clinical investigation. SETTING:
      Medical intensive care unit in a university teaching hospital. PATIENTS: 40
      consecutive patients with documented septic shock requiring at least hemodynamic
      resuscitation and respiratory support. INTERVENTIONS: There were no
      interventions. MEASUREMENTS AND RESULTS: Basal cortisol concentrations were
      increased with a mean value of 36.8 micrograms/dl (range 7.9-113). Of the overall
      cortisol determinations 92% were above 15 micrograms/dl. No statistically
      significant differences in basal cortisol concentrations were found when
      survival, type of infection, and positive blood cultures were considered.
      Patients with hepatic disease had significantly higher cortisol (50.1 (+/- 6.2)
      micrograms/dl versus 35.9(+/- 3.3) micrograms/dl, p = 0.035) levels compared to
      other patients. No correlations were found between basal plasma cortisol
      concentrations and factors such as SAPS, OSF, hemodynamic measurements, duration
      of shock, and amount of vasopressor and/or inotropic agents. Cortisol
      concentrations had significant but weak correlation with ACTH levels in survivors
      (r = 0.4; p = 0.03; n = 28) but not in non-survivors (r = 0.03; p = 0.85; n =
      52). Cortisol levels in non-survivors increased significantly from enrollment
      time to the 72nd hour of the survey (day 1: 38.9(+/- 3.8) micrograms/dl versus
      day 3: 66.7(+/- 17.1) micrograms/dl; p = 0.046) and were significantly higher
      than those recorded in survivors. Responses to the short ACTH stimulation test
      were not significantly different between survivors and non-survivors. According
      to the different criteria used to interpret the response to the ACTH stimulation
      test, incidence of adrenocortical insufficiency was highly variable ranging from
      6.25-75% in patients with septic shock. Only one patient had absolute
      adrenocortical insufficiency (basal cortisol level below 10 micrograms/dl;
      response to the ACTH stimulation test below 18 micrograms/dl). CONCLUSION: Our
      data suggest that in a selected population of patients with severe septic shock
      single plasma cortisol determination has no predictive value. The short ACTH
      stimulation test performed within the first 24 h of onset shock can neither
      predict outcome nor estimate impairment in adrenocortical function in patients
      with high basal cortisol level. Adrenal insufficiency is rare in septic shock and
      should be suspected when cortisol level is below 15 micrograms/dl and then
      confirmed by a peak cortisol level lower than 18 micrograms/dl during the short
      ACTH stimulation test.

PMID- 7560476
TI  - Pronounced elevation in circulating calcitonin in critical care patients is
      related to the severity of illness and survival.
AB  - OBJECTIVE: To study circulating levels of calcitonin in critically ill patients
      in relation to the severity of illness and survival. DESIGN: Cross-sectional and
      prospective. SETTING: The ICU in Gavle hospital, a secondary non-teaching
      hospital. PATIENTS: 37 consecutive ICU patients. MEASUREMENTS AND RESULTS: Serum
      calcium and immunoreactive calcitonin (iCT) were measured and the Apache II and
      the Multiple Organ Failure (MOF) scores were recorded during the first 24 h in
      the ICU. Patients were followed for hospital survival. Profound increase in
      circulating iCT was seen (mean 591, median 184, range 8-3445 pg/ml) in the
      studied sample and only 11% of the patients showed normal levels (< 40 pg/ml).
      iCT was higher in septic than nonseptic patients (p < 0.004) and was correlated
      to two indices of severity of illness (r = 0.50, p < 0.006 versus the Apache II
      score and p = 0.55, p < 0.003 versus the MOF score). Furthermore, iCT was
      correlated to the length of stay in the intensive care unit (r = 0.56, p < 0.001)
      and was elevated in the patients who did not survive when compared to survivors
      (p < 0.03). iCT was not significantly related to the degree of serum calcium
      (mean 2.22 +/- 0.15 SD mmol/l). Gel chromatography in a fast protein liquid
      chromatography (FPLC) system of serum from 4 patients with elevated iCT disclosed
      that a majority of the measured CT was not due to monomeric CT, but high
      molecular CT. CONCLUSIONS: Pronounced elevations in circulating iCT were seen
      during the first 24 h critically ill patients. As the major part of the iCT
      consisted of high molecular weight CT this would not induce hypocalcemia. Rather,
      the elevated iCT would be regarded as a part of the metabolic responses to
      illness.

PMID- 7560477
TI  - Comparative evaluation of the haemodynamic effects of continuous negative
      external pressure (CNEP) and positive end-expiratory pressure (PEEP) in
      mechanically ventilated trauma patients.
AB  - OBJECTIVE: To compare the haemodynamic effects of identical values of continuous
      negative external pressure (CNEP) and positive end-expiratory pressure (PEEP) in
      a group of mechanically ventilated patients. SETTING: General ICU, Vicenza
      Hospital, Italy. PATIENTS: 15 consecutive patients, admitted after road accident
      trauma. METHODS: We compared the haemodynamic effects of ZEEP, 10 cmH2O of PEEP,
      and 10 cmH2O CNEP, applied in random order, in 15 head trauma patients under
      going controlled mechanical ventilation; 9 had associated thoracic trauma, while
      6 did not have lung involvement. CNEP was obtained with a "poncho". RESULTS: We
      observed a significant increase in CI during CNEP, compared with both ZEEP and
      PEEP 10 cmH2O. Accordingly the oxygen delivery index significantly increased
      during CNEP, compared with PEEP 10 cmH2O. Conversely, Qs/Qt decreased with CNEP,
      if compared with PEEP, both in patients with and without lung damage. CONCLUSION:
      CNEP can significantly increase CI in mechanically ventilated patients in
      patients with and without associated lung damage.

PMID- 7560478
TI  - European participation in major intensive care journals.
AB  - To evaluate the recent evolution of the European contribution to the
      international literature in intensive care medicine, we reviewed the source of
      all original articles and case reports published from 1989 to 1993 in 5 major
      journals: Critical Care Medicine, Intensive Care Medicine, Chest, The American
      Review of Respiratory Disease and Circulatory Shock. There was an overall decline
      in the US contributions and a corresponding increase in the European
      participations to Chest and the American Review of Respiratory Disease, but not
      to Critical Care Medicine or Circulatory Shock. The European participation to
      Intensive Care Medicine remained largely predominant. The evaluation of the
      contributions of major European countries to these 5 journals revealed a
      progressive increase in the French, Italian and Spanish contributions, whilst the
      German contribution remained stable and the UK contributions decreased. The UK
      contribution, which was the first in 1989, became second in 1993, after France.

PMID- 7560479
TI  - Differences in oxygen content between mixed venous blood and cerebral venous
      blood for outcome prediction after cardiac arrest.
AB  - OBJECTIVE: To assess the usefulness of differences in oxygen content between
      mixed venous blood and cerebral venous blood for predicting neurological outcome
      after cardiac arrest. DESIGN: Observational study. SETTING: Medical-surgical
      intensive care unit (IUC) in a university hospital. PATIENTS AND PARTICIPANTS: 34
      acutely comatose patients who had been admitted to the ICU after cardiac arrest
      and successful cardiopulmonary resuscitation, classified according to outcome
      (group A, brain death; group B, vegetative state; group C, neurological
      recovery). MEASUREMENTS AND RESULTS: Between 6 and 18 h (mean 12 +/- 16.3 h)
      after hemodynamic stability and 24 h later, the patient's neurological status was
      assessed by means of the Glasgow Coma Scale and blood gas analysis, partial
      pressure of O2, oxygen content in venous blood from the jugular bulb and mixed
      venous blood, O2 saturation, and lactate and creatine kinase activity (CK) in CSF
      were determined. Group C patients had significantly lower lactate and CK levels
      in CSF as compared with patients in groups A and B. Mean oxygen content in mixed
      venous blood was higher than that in cerebral venous blood in group C patients,
      whereas the opposite was found in patients with unfavourable outcome. A positive
      difference in oxygen content between mixed venous blood and cerebral venous blood
      showed a sensitivity of 95%, specificity of 100%, positive predictive value of
      100%, and negative predictive value of 92% for predicting recovery of
      consciousness. CONCLUSIONS: Differences between oxygen content of blood samples
      from the pulmonary artery and the jugular bulb is a simple measurement that has
      provided good accuracy in the outcome prediction of brain damage after cardiac
      arrest treated by resuscitation.

PMID- 7560480
TI  - Significance of electrical brain activity in brain-stem death.
AB  - A 46-year-old man was diagnosed clinically brain dead after sustaining head
      trauma. The patient was in deep coma, brain nerves were unresponsive and
      spontaneous breathing was absent. However, EEG showed well preserved activity,
      but no reactivity to external stimuli. EEG activity disappeared within 40 h. BAEP
      were highly abnormal, flash-VEP as recorded 3 h after the diagnosis of brain stem
      death was of high amplitude but of simplified form. The neurophysiological
      findings revealed that the main reason for deep coma was brain stem damage while
      cortical activity was still present. This condition raises ethical questions when
      brain death is diagnosed clinically prior to removal of organs for
      transplantation.

PMID- 7560481
TI  - Rupture of pulmonary artery induced by balloon occlusion pulmonary angiography.
AB  - A case of pulmonary artery rupture induced by balloon occlusion pulmonary
      angiography (BOPA) is reported. A flow-directed pulmonary artery catheter had
      been inserted for hemodynamic monitoring in a septic shock patient complicated by
      acute respiratory distress syndrome. To check for pulmonary damage, BOPA was
      performed immediately after hemodynamic measurement. Just as the hand injection
      of contrast medium was ending, the patient began to cough and a small amount of
      hemoptysis was observed. The angiogram showed the extravasation of contrast
      medium from the distal pulmonary artery to the situation of catheter tip.
      Pulmonary hemorrhage was controlled with mechanical ventilatory support with 10
      cmH2O positive end-expiratory pressure and no specific therapy was required. This
      complication should be kept in mind and using a power injector to avoid injurious
      transient high pressure pulse is recommended.

PMID- 7560482
TI  - Fatal cerebellar infarction in a migraine sufferer whilst receiving sumatriptan.
AB  - This is a case report of a 39-year-old man who suffered from a fatal cerebellar
      infarction whilst on sumatriptan therapy for an acute attack of migraine.
      Intracranial vasospasm is proposed as the likely causative mechanism and possible
      therapeutic intervention is highlighted.

PMID- 7560484
TI  - High-dose intravenous magnesium sulfate in the management of life-threatening
      status asthmaticus.

PMID- 7560485
TI  - Spontaneous rupture of the liver during pregnancy.

PMID- 7560483
TI  - Maintaining blood flow in the extracorporeal circuit: haemostasis and
      anticoagulation.
AB  - OBJECTIVES: To review the methods and developments in maintaining extracorporeal
      circuits in critically ill patients. DESIGN: The review includes details of the
      pathophysiological processes of haemostasis and coagulation in critically ill
      patients, methods of maintaining blood flow in the extracorporeal circuit and
      methods of monitoring anticoagulation agents used. SETTING: Information is
      relevant to the management of critically ill patients requiring extracorporeal
      renal and respiratory support and cardiopulmonary bypass. CONCLUSIONS: Heparin is
      the mainstay of anticoagulation for the extracorporeal circuit although the
      complex abnormalities of the coagulation system in critically ill patients are
      associated with a considerable risk of bleeding. Alternative therapeutic agents
      and physical strategies (prostacyclin, low molecular weight heparin, sodium
      citrate, regional anticoagulation, heparin bonding and attention to circuit
      design) may reduce the risk of bleeding but expense and difficulty in monitoring
      are disadvantages.

PMID- 7560486
TI  - Are autoimmune mechanisms involved in critical illness polyneuropathy?

PMID- 7560487
TI  - False aneurysm of the brachial artery after an attempt to place an axillary
      venous access.

PMID- 7560488
TI  - Prophylactic bronchial hygiene following cardiac surgery: what is necessary?

PMID- 7560490
TI  - Late outcome of percutaneous dilatational tracheostomy in intensive care
      patients.
AB  - OBJECTIVE: Percutaneous dilatational tracheostomy is increasingly practiced in
      intensive care units and has a low incidence of early complications. The late
      effects of this procedure are still poorly known and were the focus of this
      study. DESIGN: Prospective descriptive clinical study. SETTING: Interdisciplinary
      intensive care unit in a 300-bed teaching hospital. PATIENTS: A consecutive group
      of critically ill patients who underwent percutaneous tracheostomy between Nov.
      90 and March 93, surviving at least 2 months after decannulation. MEASUREMENTS
      AND RESULTS: There were 17 patients fulfilling the inclusion criteria and 16 of
      them were seen and examined. The follow-up protocol required a formal
      standardized patient interview, a physical examination of the stoma site and a
      fiberoptic laryngotracheoscopy. Results of these sub-tests and overall outcome
      rating were standardized and expressed as good, moderate or poor. Subjective
      rating was good in all patients. All denied suffering from any side effects of
      their tracheostomy. Clinical examination revealed neither stridor nor hoarseness
      in any of the patients. Most of the scars were whitish and less than 1 cm in
      length, a few were sunken in, none had adhesions. In 15 patients the clinical
      result was good and in one, moderate (whitish, sunken-in scar, longer than 2 cm).
      Ten patients underwent tracheoscopy, while 6 did not. There were no signs of
      significant stenosis or tracheomalacia. In 8 patients with minor findings results
      were scored as good, while 2 were classified as moderate (combination of swelling
      and scar formation of a string-like membrane). The overall rating was good in 13
      patients (81%) and moderate in 3 patients (19%). There were no poor outcomes.
      CONCLUSIONS: Late outcome of percutaneous dilatational tracheostomy in critically
      ill patients is mostly good. Pending further studies, the use of this technique
      in intensive care units appears justified.

PMID- 7560489
TI  - Mask physiotherapy in patients after heart surgery: a controlled study.
AB  - OBJECTIVE: Investigate the effects of mask physiotherapy on post-operative
      complications after thoracic surgery. DESIGN: A prospective, consecutive,
      randomized, controlled study. SETTING: Department of Thoracic and Heart Surgery
      at a University Hospital. The treatments were performed by experienced and
      specially trained physiotherapists. PATIENTS: 97 low-risk male patients
      undergoing coronary artery by-pass graft surgery were evaluated. 66 patients
      completed the study. INTERVENTIONS: The patients were treated with routine chest
      physiotherapy alone or supplied with either positive expiratory pressure (PEP),
      or inspiratory resistance-positive expiratory pressure (IR-PEP). MEASUREMENTS AND
      RESULTS: Post-operative pulmonary complications were assessed by forced vital
      capacity (FVC), arterial oxygen tension (PaO2), and chest X-ray examination, all
      measured pre-operatively and on the third and sixth post-operative day. There was
      an almost equal decrease and subsequent rise in spirometric and blood gas values,
      but patients treated with the PEP mask had a borderly significantly higher
      increase in PaO2 from day 3 to day 6 compared with patients treated with no mask.
      There was an almost equal frequency of atelectasis in the 3 treatments. The
      patients filled in a questionaire expressing their opinion about their treatment.
      Most patients liked their treatment and found it helpful but a little less so in
      the IR-PEP group. CONCLUSION: We did not find any significant difference between
      the three groups; however, a tendency to decreased risk of having post-operative
      complications was observed in the groups having positive expiratory pressure
      (PEP) and inspiratory resistance-positive expiratory pressure (IR-PEP).

PMID- 7560491
TI  - Ultrastructure and mucociliary transport of bronchial respiratory epithelium in
      intubated patients.
AB  - OBJECTIVE: The objective of this study was to investigate whether reduced
      bronchial mucus transport velocity (BTV) is associated with a loss of cilia or
      ultrastructural abnormalities of cilia in intubated patients. DESIGN: The
      patients were studied prospectively in a convenience sample trial. SETTING: The
      study took place in a university hospital. PATIENTS AND PARTICIPANTS: 29 orally
      intubated patients in a surgical ICU. INTERVENTIONS: BTV was measured with
      radiolabeled microspheres in the right and left primary bronchus. Following these
      measurements, biopsy samples were taken from the bronchi for scanning (SEM) and
      transmission (TEM) electron-microscopic investigations. MEASUREMENTS AND RESULTS:
      SEM: Patients with normal or slight impaired BTV (group 1, n = 14: BTV: 8.5
      mm/min (3.8-11.5); median with range) showed more cilia on the luminal surface
      than patients with markedly depressed BTV (p < 0.05) (group 2, n = 15: BTV: 0 (0
      2.1)). The difference was statistically significant. The BTV values correlated
      moderately with the number of cilia on the luminal surface (r = 0.46; p = 0.02).
      TEM: In group 1, 6.5% (3.9-14.9) of cilia were abnormal (median with range) vs
      9.3% (4.9-13.7) in group 2; these differences were not statistically significant.
      Neither was there any significant correlation between BTV and the frequency of
      abnormal cilia. CONCLUSIONS: Impaired mucociliary transport in intubated patients
      is associated with a loss of cilia rather than ultrastructural abnormalities of
      cilia, which are less relevant.

PMID- 7560492
TI  - Acute renal failure in infancy: treatment by continuous renal replacement
      therapy.

PMID- 7560493
TI  - Blood filtration in children with severe sepsis: safe adjunctive therapy.
AB  - OBJECTIVE: To review the safety and efficacy of haemofiltration and
      plasmafiltration in children with severe sepsis. DESIGN: Retrospective case notes
      analysis. SETTING: University Paediatric Intensive Care Unit. PATIENTS: All
      children admitted to the intensive care unit between November 1985 and May 1992
      with a primary diagnosis of severe sepsis who also received blood filtration
      therapy. INTERVENTIONS: Continuous haemofiltration (HF) 18 patients; continuous
      haemofiltration and plasmafiltration (PF) 9 patients. MEASUREMENTS AND RESULTS:
      27 children with sepsis-induced MOSF, median age 26.6 months (range 0.33-185),
      median weight 12 kg (range 2.5-58), mean PRISM score 19.4 (SD 8.6), mean number
      of organs failing 2.78 (SD 0.9) received filtration for a median duration of 36
      hours (range 2-145). Eight (30%) survived (HF 5/18, PF 3/9). There was no
      significant difference in the demographic features between the HF group and the
      PF group and no difference in mortality. The two groups were pooled to assess the
      effect of commencement of filtration on clinical wellbeing. Arterial blood gases,
      electrolytes, full blood examination, ventilator settings and doses of inotropes
      were recorded immediately prior to commencement of filtration and 18 h after
      commencement. Serum anion gap and osmolality were calculated using conventional
      formulae. There were no significant changes in the level of cardiorespiratory
      support, or biochemical markers of severity following commencement of filtration.
      Platelet count fell 32% (p = 0.029) but no bleeding was encountered. No severe
      complications were observed during 1222 h of filtration. No bleeding or infection
      was observed at the site of cannulation. One child developed haemodynamic
      instability following commencement of plasmafiltration necessitating abandonment
      of the procedure. CONCLUSION: Haemofiltration or plasmafiltration can be
      performed safely in children with severe sepsis but their effect on outcome
      remains unknown.

PMID- 7560494
TI  - Hemodynamic effects of high-frequency oscillatory ventilation in severe pediatric
      respiratory failure.
AB  - OBJECTIVE: To assess the hemodynamic effects of high mean proximal airway
      pressures (Paw) during high-frequency oscillatory ventilation (HFOV) in non
      neonatal pediatrics patients with severe respiratory failure. DESIGN: Prospective
      and retrospective study. SETTING: Pediatric ICU in a university-affiliated
      hospital. PATIENTS: 8 non-neonatal pediatric patients with severe respiratory
      failure ventilated with HFOV at our institution between July 1991 and February
      1994. All patients had a pulmonary artery catheter. INTERVENTIONS: HFOV.
      MEASUREMENTS AND RESULTS: Higher Paw was required during HFOV to obtain adequate
      lung expansion during the first 24 h (median 20.9 cmH2O, range 16.9-30.0 cmH2O in
      CMV, versus median 30.0 cmH2O, range 21.0-33.0 cmH2O in HFOV, p = 0.008),
      resulting in improved oxygenation as evaluated by alveolar-arterial oxygen
      difference (median of 557.2 mmHg, range 360.4-607.8 mmHg in CMV, versus median of
      410.5 mmHg, range 282.9-550.2 mmHg after 24 h of HFOV, p = 0.03). The only
      observed effect on the cardiovascular system was a decrease in heart rate (median
      of 162, range 129-178 in CMV, versus median of 142, range 104-195 after 24 h of
      HFOV, p = 0.03). Oxygen delivery, cardiac index, mean systemic arterial blood
      pressure, and pulmonary and systemic vascular resistances did not change
      significantly before and after HFOV in the patients as a group, although in one
      case a decrease in cardiac index and oxygen delivery was observed. CONCLUSIONS:
      High-Paw HFOV must be used cautiously, but seems to have no discernible adverse
      effects on the cardiovascular system in most patients.

PMID- 7560495
TI  - Effects of theophylline on renal insufficiency in neonates with respiratory
      distress syndrome.
AB  - We report here 6 cases of critically ill newborn infants with both RDS and acute
      renal insufficiency, unresponsive to conventional treatment (furosemide,
      dopamine). Theophylline, an adenosine antagonist, has been shown to prevent
      hypoxemia-induced renal insufficiency in rabbits and our patients thus received
      compassionately a low-dose of theophylline (1 mg . kg-1 i.v.). Urinary water
      excretion and creatinine clearances increased significantly in 5 out of 6
      neonates, thus suggesting a beneficial role of theophylline in neonatal prerenal
      failure.

PMID- 7560496
TI  - Extreme polyuria: decompensated diabetes mellitus and/or diabetes insipidus?

PMID- 7560498
TI  - Validation of a simple method assessing nitric oxide and nitrogen dioxide
      concentrations.
AB  - Monitoring of nitric oxide (NO) and nitrogen dioxide (NO2) is a prerequisite for
      the clinical use of NO. Chemiluminescence, the reference method, cannot be used
      as a routine in clinical practice in view of its cost and other restraints. This
      study was performed to evaluate a device using an electrochemical method
      (Polytrons NO and NO2, Drager). Forty-nine simultaneous measurements of NO and
      various oxides of nitrogen (NOx) concentrations by the two apparatus were
      performed. NO measurements by means of these two methods are very well correlated
      (r = 0.96; p < 10(-5)). The mean difference according to the method of Bland and
      Altman was 2.8 +/- 1.7 ppm, with the limits of agreement at -0.6 and +6.2 ppm
      (confidence interval of 95%). There was also a good correlation between
      measurements of NO2 obtained via Polytrons and NOx via chemiluminescence (r =
      0.84; p < 10(-5)). However, NO2 measurements obtained via Polytrons may be
      insufficient to exclude potential toxicity of NO2 due to the inability to detect
      measurements in the ppb-range. This study demonstrates that devices designed for
      industrial purposes (Polytrons NO and NO2, Drager) can be used for clinical
      purposes.

PMID- 7560497
TI  - Intrinsic positive end-expiratory pressure (PEEPi).

PMID- 7560499
TI  - Heparin-induced thrombocytopenia type II: successful use of Orgaran (ORG 10172)
      in intensive care patients.

PMID- 7560500
TI  - Bleeding from the gastrointestinal tract during prolonged ventilation.

PMID- 7560501
TI  - Performance of ultrasonic speckle tracking in various tissues.
AB  - The purpose of this study was to investigate the accuracy of ultrasound speckle
      tracking in various tissues. Results from two-dimensional tissue speckle tracking
      in liver, muscle, fat, and sponge samples are presented, while keeping other
      speckle tracking parameters constant. Speckle tracking performance was
      characterized both in terms of the magnitude of tracking errors and in terms of
      the percentage of correctly tracked displacement vectors. Speckle tracking in
      muscle tissue, which contains myofibrils and significant tissue microstructure,
      produced the highest percentage of correctly tracked vectors and smallest
      tracking errors relative to other tissues.

PMID- 7560502
TI  - Time and frequency domain characteristics of sperm whale clicks.
AB  - Regular clicks from diving sperm whales, both large bull males and smaller
      females, were recorded in deep oceanic water off the Azores and subsequently
      sampled to computer disks for digital analysis. A total of 8540 clicks were
      marked and analyzed. Simple temporal analysis of the interclick intervals during
      feeding dives revealed mean click rates for male sperm whales of 1.1713 s-1 and
      1.9455 s-1 for females. Fourier analysis showed distinctive peaks in the spectra
      of bull male sperm whales at 400 Hz and 2 kHz which were stable over extended
      periods of up to 20 mins. The clicks contained higher frequency components with
      energy ranging up to at least 12 kHz but not concentrated at any sharply defined
      frequency. The clicks of smaller female sperm whales showed similar spectral
      peaks, shifted to 1.2 and 3 kHz, respectively, but these peaks were less
      pronounced than those in the male click spectra and less stable with time. Higher
      frequencies were also present up to at least 15 kHz. The previously reported
      multiple pulse structure of sperm whale clicks is confirmed, but digital
      filtering reveals this structure to be frequency dependent. Analysis using the
      short-time Fourier transform confirms the complex time-frequency structure of
      individual clicks. The frequencies at which the multiples emerge in male and
      female clicks supports the idea of air cavities in the sperm whale head acting as
      sound reflectors, although the magnitude of the second pulse at high frequencies
      suggests some form of off axis distortion. It is also possible that air cavity
      resonance in the head of the sperm whale may act to reinforce the high-frequency
      components of the click, and that such components may have superior range and
      resolution performance in terms of echolocation.

PMID- 7560503
TI  - Effect of relative and overall amplitude on perception of voiceless stop
      consonants by listeners with normal and impaired hearing.
AB  - Previous studies of the /p/-/t/ contrast for normal-hearing listeners have shown
      that both manipulation of the amplitude of the burst relative to the vowel in the
      F4-F5 frequency region and overall presentation level can influence the
      perception of place of articulation [R. N. Ohde and K. N. Stevens, J. Acoust.
      Soc. Am. 74, 706-714 (1983); Gravel and Ohde, Asha 25, 101 (1983)], such that
      greater burst amplitude in the high frequencies and higher presentation levels
      result in more alveolar responses. The influence of relative amplitude and
      presentation level was tested for both normal-hearing (NH) and hearing-impaired
      (HI) listeners in the present study. Synthetic CV stimuli were used, and the
      amplitude of the burst relative to vowel-onset amplitude in the F4-F5 frequency
      region was manipulated across a 20-dB range. In addition, overall presentation
      level was varied across a 45-dB range. The findings revealed that the hearing
      impaired listeners selected more alveolar responses than listeners with normal
      hearing when tested at equivalent SPLs. A group of five normal-hearing listeners
      were then presented the synthetic stimuli in a background of broadband noise at a
      level that produced thresholds at 4 kHz equivalent to the thresholds of five
      hearing-impaired listeners. Results from the noise-masked normal-hearing
      listeners did not consistently show more alveolar responses as presentation level
      of the stimuli was increased, thus failing to mimic the responses from the
      hearing-impaired listeners in quiet.

PMID- 7560504
TI  - Articulatory organization of mandibular, labial, and velar movements during
      speech.
AB  - It has been shown that articulator movements during speech are adjusted along a
      number of spatiotemporal dimensions. For example, variations in the extent of
      lip, jaw, or tongue motion are associated with proportional changes in the
      respective articulators' peak velocity. Modifications in the timing of lip and
      jaw actions are apparently constrained, exhibiting relative timing covariation.
      Syllable prominence systematically affects some combination of the articular
      motion parameters, i.e., extent, speed, and duration. The present investigation
      is an attempt to extend observations of the spatiotemporal properties of
      articulator movement to include the velum. Lip, jaw, and velar kinematics were
      recorded optoelectronically and simultaneously with the acoustic signal during
      productions of the utterance/mabnab/. The spatial and temporal relations between
      the lips, the jaw, and the velum were examined and compared across articulators.
      For movements associated with each syllable, the velum displayed scaling pattern
      qualitatively similar to those of the lips and jaw. Moreover, velocity
      displacement relations were more robust for the lowering than for the raising
      movements of the velum. There was evidence of interarticulator coupling between
      the velum and the jaw, and between the velum and the upper lip, although this
      coupling was not as strong as that observed among the oral articulators.
      Articulator specific differences in velocity-displacement correlations and degree
      of interarticulator cohesion for the various movement phases may be related to a
      combination of aerodynamic and phonetic factors, such as the phonologically
      noncontrastive nature of nasalization in English.

PMID- 7560505
TI  - Durations of young children's word and nonword vocalizations.
AB  - The duration of word (W) and nonword (NW) forms was examined in the monthly
      vocalizations of seven children between 8 and 26 months of age. The W (i.e.,
      glossable "adultlike") forms and NW (i.e., nonglossable but phonetically
      transcribable) forms occurring in each child's consonant+vowel (CV) vocalizations
      were measured. The results were that W durations significantly decreased as a
      function of increasing chronological age. On the other hand, NW durations were
      not correlated with increasing age. The meaningfulness corresponding to W forms
      is hypothesized to account for the results.

PMID- 7560506
TI  - Pure tone masking patterns in adult chickens before and after recovery from
      acoustic trauma.
AB  - Three female adult chickens were trained to detect pure tones using a positive
      reinforcement technique and an adaptive threshold tracking procedure. Masked
      thresholds for tone bursts were measured in the presence of pure-tone maskers at
      500, 1000, and 2000 Hz. Masker levels of 40-, 60-, and 70-dB sound-pressure level
      (SPL) were employed. Masking was maximal at the frequency of the masker. Tone-on
      tone masking patterns were symmetrical at low masker levels, but at higher masker
      levels, more masking was evident at frequencies above the masker than below the
      masker. Distinct low threshold notches were frequently observed above and below
      the peak in the masking pattern. After the normal masking patterns had been
      measured, the chickens were exposed to a 525-Hz traumatizing tone at 120 dB SPL
      for 48 h and then allowed to recover. After thresholds had returned to their pre
      exposure levels, tone-on-tone masking patterns were remeasured. The post-exposure
      masking patterns were virtually identical to the pre-exposure masking patterns.

PMID- 7560507
TI  - Infants' pitch perception: inharmonic tonal complexes.
AB  - Two experiments assessed the effects of inharmonicity on 7- to 8-month-old
      infants' perception of the pitch of tonal complexes. A number of harmonic and
      inharmonic complexes were presented in a visually reinforced operant head turn
      procedure. In both experiments, infants demonstrated the ability to discriminate
      two harmonic complexes based on missing fundamental frequencies of 160 and 200
      Hz. After learning this basic task, infants learned to discriminate inharmonic
      complexes, which were created by shifting the partials of the harmonic complexes
      upward by 30 Hz (experiment 1) or 20 Hz (experiment 2). Finally, three spectrally
      different inharmonic complexes represented each pitch, and infants attempted to
      categorize those complexes according to their pitches. In both experiments,
      infants successfully discriminated the pitches of the spectrally varying tonal
      complexes, but their performance deteriorated for the more strongly inharmonic
      complexes of experiment 1. These results suggest that, as for adults, the
      salience of pitch for inharmonic sounds decreases with increasing inharmonicity.

PMID- 7560508
TI  - The perception of amplified speech by listeners with hearing loss: acoustic
      correlates.
AB  - Audibility-based approaches to hearing-aid selection generally have focused on
      the long-term average speech spectrum (LTASS). Advances in amplification
      technology (e.g., multiband signal processing, level-dependent frequency shaping,
      full dynamic range compression, adaptive compression) make it difficult to
      predict the audibility of short-term components of speech from the amplified
      LTASS. This study was designed to quantify the audibility of a specific phonemes
      as processed by two different hearing-aid circuits (linear and full dynamic range
      compression), and to investigate the relation between audibility and performance
      on a nonsense syllable recognition task. Data were obtained from three subjects
      with moderate sensorineural hearing loss. Nine unvoiced consonants were presented
      in two vowel contexts (/i/ and /a/) in both the pre- and post-vocalic position at
      three intensities. While the performance on selected conditions appeared to vary
      by hearing-aid type, only one subject showed a statistically significant
      difference between the two hearing-aid systems. Acoustic analyses revealed a
      variety of spectral and temporal changes to the speech signal following
      processing. Estimates of audibility were based upon each subject's thresholds and
      an acoustic analysis of the amplified signal that varied across phonemes and
      consonant position. A signal detection approach was used to predict performance
      from a simple measure of audibility.

PMID- 7560509
TI  - On equivalence of locally active models of the cochlea.
AB  - In the literature on locally active models of the cochlea several forms of the
      model have been worked out in which elements of the organ of Corti are assumed to
      produce acoustical energy. In these models use is made of a secondary resonance
      or a place-dependent delay to achieve activity over a limited part of the length
      of the basilar membrane, and outer hair cells are postulated as sources of energy
      production. In the present paper it will be shown that several of these models
      are formally equivalent. That means that they can be reduced to a standard form,
      and that the only difference resides in the choice and meaning of the parameters.
      The results of the analysis serve to facilitate the analysis of function and
      structure in cochlear models containing sources of local activity. In particular,
      questions of positive versus negative feedback, and the parts played by resonance
      and impedance-level differences can be resolved unambiguously. The treatment can
      be extended to models with higher dimensionality, and can also serve to obtain
      insight in nonlinear phenomena occurring in cochlear models.

PMID- 7560510
TI  - Transient effects during the chopping response of LSO neurons.
AB  - The initial transient chopping response of LSO neuron discharges to both monaural
      and binaural tone-burst stimuli in the context of a previously developed point
      process model of the later sustained response is analyzed and modeled. The
      analysis reveals the nature of the initial transient response to stimulus onset:
      The model's stimulus-dependent parameters vary with poststimulus-onset time while
      the neuron's intrinsic recovery characteristics remain constant throughout the
      response. By applying maximum-likelihood estimation techniques to determine the
      time course of the stimulus-dependent parameters, it was found that the initial
      excitatory and inhibitory effects decay exponentially, with their ratio
      determining the instantaneous rate of firing and their relative latency
      determining the extent of the initial chopping pattern. The "absolute" and
      apparent deadtime also vary exponentially during the transient portion of the
      response. It is concluded that the recovery characteristics of LSO neurons and,
      the exponential nature of the transient effects give rise to a tightly
      distributed latency period and a regular chopping response pattern that could
      encode azimuthal information.

PMID- 7560511
TI  - Spatially dependent acoustic cues generated by the external ear of the big brown
      bat, Eptesicus fuscus.
AB  - To measure the directionality of the external ear of the echolocating bat,
      Eptesicus fuscus, the left or right eardrum of a dead bat was replaced by a
      microphone which recorded signals received from a sound source that was moved
      around the stationary head. The test signal was a 0.5-ms FM sweep from 100 kHz to
      10 kHz (covering all frequencies in the bat's biosonar sounds). Notches and peaks
      in transfer functions for 7 tested ears varied systematically with changes in
      elevation. For the most prominent notch, center frequency decreased from about 50
      kHz for elevations at or near the horizontal to 30-40 kHz for elevations 30
      degrees-40 degrees below the horizontal. A second notch shifted from about 85 kHz
      to 70 kHz over these same elevations. Above the horizontal, a peak that flanks
      these notches changed in amplitude by 15 dB with changes in elevation. Removal of
      the tragus from the external ear disrupted the systematic movement of notch
      frequencies with elevation but did not disrupt changes in the peak's amplitude.
      Smaller changes in notch frequency also occurred with changes in azimuth, so
      monaural notch information alone cannot determine the position of sound sources
      away from the median plane. However, because bats routinely keep the head pointed
      at the target's azimuth, median-plane localization occurs with monaural cues
      delivered to the two ears. Corresponding changes with elevation occurred in the
      impulse-response, which consists of a series of 3-6 peaks spaced 10-20
      microseconds apart. The time separation of two prominent impulse peaks
      systematically increased from 22-26 microseconds above the horizontal to about 36
      40 microseconds below the horizontal, and removal of the tragus disrupted this
      time shift below the horizontal.

PMID- 7560512
TI  - Speech intelligibility in noise: relative contribution of speech elements above
      and below the noise level.

PMID- 7560513
TI  - The effects of sinusoidal amplitude modulation on gap detection in noise.

PMID- 7560514
TI  - Some considerations on the use of adaptive methods for estimating interaural
      delay thresholds.

PMID- 7560515
TI  - Forty years on: reflections on national health service management.

PMID- 7560516
TI  - The life situation of a long-term psychiatric patient: some restrictions in, and
      possibilities of, open care.
AB  - This paper describes and analyses, from a sociocultural viewpoint, the ways of
      life of discharged long-term psychiatric patients in northern Finland. The paper
      focuses on subjectivity: control of life and fundamental experiences in life. The
      data consist of interviews with 25 outpatients who have moved to live in
      residential homes, rehabilitation centres or their own homes after receiving
      preparatory training in the psychiatric hospital. The findings suggest that the
      way of life of the outpatients did not significantly differ from that of other
      people belonging to the same generation of Finns. With respect to control of
      life, a conspicuous feature was the strong tendency to let themselves be led by
      others, and to self-sacrifice for the good of others. For the patients,
      independence was the best aspect of open care. Fear for being branded as a
      psychiatric case or as a former mental patient threatened the patients' external
      control of life. The central element of control of life of the Finns is work. The
      outpatients thought work a matter of honour and they did not find their present,
      inactive way of life satisfactory.

PMID- 7560517
TI  - Control and restraint in contemporary psychiatric nursing: some ethical
      considerations.
AB  - This paper begins with an exploration of current attitudes towards the use of
      physical restraint in psychiatric nursing, and the contributions which the 1985
      Ritchie Report and the 1991 Report of the Committee Of Inquiry Into Ashworth
      Hospital have made to the debate on the use of control and restraint within
      psychiatric institutions. The main focus of the paper, though, is an evaluation
      of the ethical justifications for and the ethical and political objections to the
      use of physical restraint techniques as a response to aggressive and self
      injurious behaviour in contemporary mental health nursing practice. The author
      concludes that the number of situations where control and restraint techniques
      are used might be reduced by the development of new therapeutic approaches. Such
      approaches should allow for more negotiation regarding care between clients and
      nurses, and acknowledge the potential benefits of clients resisting supposedly
      therapeutic interventions which they find unhelpful.

PMID- 7560518
TI  - Supporting one another: the nature of family work when a young adult has cancer.
AB  - Families, and the support they provide, are one of the most important resources
      of the informal health care delivery system. As nurses we are called upon to
      enable clients to maximize their use of family resources and to enable families
      to cope with illness-related events. While research has clearly documented the
      important role of support in enabling persons to cope effectively with illnesses
      and illness-related events, further research to understand the processes of
      providing support within families has been called for. With such information we
      may be more effective in our efforts to guide and support families as they cope
      with illness in a family member. This paper was developed from a qualitative
      study with young adults with cancer that examined social relationships in order
      to understand the nature of interactions perceived as supportive and the context
      within which they occurred. In-depth interviews conducted with young adults
      provided detailed data regarding the nature of support young adults received from
      and offered to their families in order to maintain family functioning. The
      processes of offering and receiving support have been conceptualized into five
      categories of 'family work'. The nature of the work is described and the roles of
      family members in accomplishing the work are addressed. The findings are
      discussed in relation to current issues in practice.

PMID- 7560519
TI  - The paediatric oncology community nurse specialist: the influence of employment
      location and funders on models of practice.
AB  - A specialist nursing service has evolved in recent years, to care for children
      with cancer or leukaemia and their families, and co-ordinate care in the
      community. These paediatric oncology community nurse specialists (POCNS) are
      mostly based at regional children's cancer treatment centres, although some are
      based within paediatric units of district general hospitals. In addition to the
      National Health Service (NHS), a major source of funding has been provided from a
      range of charities. This paper examines the impact that the employment location
      (regional or district) and funding sources have on the process, practice and
      structure of nursing within the speciality. All 43 POCNSs were interviewed from
      28 different hospitals across the United Kingdom and Eire. Thirty-one were based
      at regional treatment centres, whilst 12 were from district general hospitals.
      Funding was provided by: the NHS (9); Cancer and Leukaemia in Childhood (CLIC)
      (10); Cancer Relief Macmillan Fund (5); and other charities (19). Major
      differences were found according to the location of POCNSs, i.e. the regional
      model and the district model, and according to funders, i.e. the Macmillan model,
      the CLIC model and the 'other funders' model. This research suggests that both
      funding source and location of POCNSs have implications for nursing practice.

PMID- 7560520
TI  - Exploring the value of clinical nursing practice: the practitioner's perspective.
AB  - This paper describes a preliminary study which attempted to explore the value of
      nursing practice from the viewpoint of practitioners. The objective was to
      further knowledge and develop insights into nursing practice, identifying
      concepts central to therapeutic care. Integral to the study was the development
      of a model for reflective practice.

PMID- 7560521
TI  - The information needs of women newly diagnosed with breast cancer.
AB  - Nurses can play a key role in patient education, including providing patients
      with useful and appropriate information. Rather than focusing on the process of
      education or information giving by nurses, this study places emphasis on the
      content of that information by taking the patients' perspective and asking the
      patients themselves what particular types of information are perceived as
      important at a specific point in time. The aim of the study was to explore what
      particular types of information were important to women newly diagnosed with
      breast cancer; to enable nurses and other health care professionals to utilize
      their time as effectively as possible and provide a high-quality service to
      individuals in their care. Women with breast cancer (a mean of 2.5 weeks from
      diagnosis) were interviewed and asked to compare items of information. The items
      of information were presented in pairs and the women stated a preference for one
      item in that pair. Thirty-six pairs were presented in total. The analysis
      involved the use of a Thurstone scaling model, which allowed rank orderings, or
      profiles of information needs, to be developed, reflecting the perceived
      importance of each item. Information about the likelihood of cure, the spread of
      the disease and treatment options were perceived as the most important items of
      information at the time of diagnosis. Other information needs, in order of
      descending priority, included information about the risk to family, side-effects
      of treatments, impact on family, self-care, effect on social life and sexual
      attractiveness. Profiles of information needs were produced to take account of
      differences in age, level of education and social class.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7560522
TI  - Management of conflict: do nurses/women handle it differently?
AB  - Conflict management has been considered an essential aspect of organizational
      life. Initially, conflict was to be avoided at all costs, but more recently
      conflict has been considered important for organizational development. This paper
      uses a case study of conflict management of nurse educators as a basis for
      contrast with the conflict managing strategies of other women, staff nurses and
      nurse managers. Other studies found that women and nurses tend to handle conflict
      using compromise and avoidance, with competition used the least often. Nurse
      managers used compromise as their major strategy for handling conflict, while the
      staff nurses used avoidance. Theories based on studies of women's socialization
      are posited to explain this phenomenon. Several implications are discussed based
      on the premise that organizational studies of conflict management that explain
      men's behaviour do not necessarily explain women's (nurses') behaviour.

PMID- 7560523
TI  - Cambodian refugees' family planning knowledge and use.
AB  - An ethnographic study was conducted within a Cambodian refugee community to
      discover information about Cambodian women's and men's knowledge and use of
      family planning methods. This 18-month study included participant observation at
      community and calendrical events, and within families' homes. Open-ended
      interviews were conducted with 53 informants from a variety of educational and
      socio-economic backgrounds. Both women and men were interviewed through a female
      bilingual interpreter when the informant lacked proficiency in speaking English.
      Major findings include a lack of knowledge among the sample about how the family
      planning methods work in the woman's body, and concerns about side-effects.
      Implications include the need to include Cambodian women and men in the planning
      and implementation of family planning programmes.

PMID- 7560524
TI  - Job satisfaction in Japanese nurses.
AB  - This study investigated job satisfaction among nurses in Japan. The instrument
      for measuring occupational satisfaction of hospital nurses developed by Stamps
      and her associates was used. Initial items were reviewed by content experts who
      were familiar with measurement of work satisfaction among health professionals
      and nursing practice in Japan. Based on the item analysis in the cultural
      context, several items were reworded or eliminated from the original version.
      Twenty-five items were retained and translated into English by bilingual
      professionals. The questionnaire was administered to 613 nurses practising in a
      large, acute-care hospital in a southern part of Japan. The results from testing
      psychometric properties of the translated version of the instrument were
      satisfactory. It may be concluded that nurses in the study were not satisfied but
      not dissatisfied either. On all items, they showed relatively strong commitment
      to their work. However, extrinsic factors such as having little opportunities for
      promotion or less favourable working conditions appeared to negatively influence
      job satisfaction in the study. The findings support the dual factor theory of
      Herzberg and also Maslow's theory. Considering the lowest scored item, little
      opportunities for promotion, which reflects the employment system in Japan,
      administrators, who are usually male medical practitioners, should be made aware
      of a need for creating clinical ladder opportunities for nurses who would be
      promoted based on a merit system, instead of the current practice of a seniority
      system.

PMID- 7560525
TI  - The nurse-doctor relationship: a selective literature review.
AB  - The disciplines of nursing and medicine are expected to work in unusually close
      proximity to one another, not just practising side by side but interacting with
      one another to achieve a common good: the health and well-being of patients. This
      selective review of literature addresses some of the issues arising from the
      frequently controversial subject of the nurse-doctor relationship and seeks to
      draw out the principal themes emerging from the application of sociological
      theory to the nurse-doctor relationship and research into its operation in
      clinical settings. Particular attention is paid to the 'doctor-nurse game', a
      stereotypical pattern of interaction, first described in the 1960s, in which
      (female) nurses learn to show initiative and offer advice, while appearing to
      defer passively to the doctor's authority. This pattern of interaction seems less
      common in clinical practice today but the problem remains of each profession
      having ideal expectations of one another which inevitably fall short as a result
      of differing views of qualities of doctors and nurses to be valued.

PMID- 7560527
TI  - A classical view of the theory-practice gap in nursing.
AB  - The perceived problem of the theory-practice gap is built upon the assumption
      that theory can and must be directly applied to nursing practice, otherwise it is
      irrelevant. Whilst the spirit in which this claim is made is healthy, the
      assumption is false. An examination of the Greek origins of theory and practice
      show that the ancient Greeks had different terms for the different types of
      knowledge contained within theory and within practice. The type of knowledge
      associated with practice could not be taught through theory, nor well represented
      in theoretical terms. The knowledge of the bicycle rider and the piano player
      illustrate this well. If this is correct then simplistic notions of 'applied
      theory' are nonsensical. The knowledge of the practitioner is not theory, but
      something else. However, there is a proper relationship between theory and
      practice, and there are clear examples of this in the way science informs nursing
      practice. The problem is that much of this is obscured by the false claim of
      theorists that nursing theory (such as normative models) is also science. In
      fact, what it represents is inadequate attempts by theory to represent knowledge
      which cannot be represented in that form. Nursing is practice, not theory. If so,
      then the term 'nursing theory' seems to be oxymoronic.

PMID- 7560526
TI  - Nurses' definitions of and attitudes towards euthanasia.
AB  - A major impetus for this study was recent literature that assumed that nurses'
      definitions of euthanasia and consequent opinions on decision making are
      unproblematic. The purpose of this study was to identify nurses' definitions of
      and attitudes towards euthanasia. Ten semi-structured interviews were conducted
      with nurses working in a variety of clinical practice settings. The majority of
      nurses could distinguish between active and passive euthanasia, but it was only
      in terms of active euthanasia that the debate was seen as significant. It was
      considered that the term passive euthanasia, particularly in relation to
      withdrawal of treatment, has served to confuse the real debate centring around
      active euthanasia. Only two participants were in favour of active euthanasia, but
      emphasized the need for 'a community of shared responsibility' in decision
      making. The major finding of the study was the commitment of all participants to
      caring for and ensuring the comfort of the dying patient. The concepts of
      ordinary and extraordinary forms of treatment and heroic measures were seen as
      worthy of debate in the context of dying with dignity rather than of euthanasia.
      There was an associated aversion to inappropriate heroic measures, which were
      perceived as prolonging death and interfering with 'dying with dignity'. The
      development of a personal and moral/ethical stance (in relation to euthanasia)
      was shown to be an evolving process embedded in a caring philosophy and
      emphasizing the contextual nature of providing appropriate care.

PMID- 7560528
TI  - An in-depth study of triangulation.
AB  - Multiple triangulation is an approach to research which is becoming increasingly
      popular among nurse researchers. It is an attempt to improve validity by
      combining various techniques in one study. Provided that the researcher is well
      informed, the approach can be successful. However, the issue becomes clouded
      because in their excitement some nurse researchers seem to have forgotten that
      the roots of research stem from one of two paradigms, or world views. This has
      led to the suggestion that paradigms may be combined, and has caused the validity
      of multiple triangulation to be called into question. In an attempt to unravel
      the muddle this paper describes multiple triangulation and goes on to suggest
      where the confusion has occurred. It concludes that multiple triangulation is a
      valid technique providing that researchers remember that their work will always
      be influenced by a single paradigm.

PMID- 7560529
TI  - Continuing the dialogue: a response to Draper's critique of Fawcett's 'Conceptual
      models and nursing practice: the reciprocal relationship'.
AB  - In their response to Draper's (1993) critique of Fawcett's (1992) paper
      'Conceptual models and nursing practice: the reciprocal relationship', the
      authors argue that Draper's critique is flawed. They point out that Draper fails
      to acknowledge the diversity within the positivist movement, makes logical leaps,
      and fails to acknowledge Fawcett's long-standing distinction between middle-range
      theories and conceptual models and her discussions of the differences in the
      criteria to be used when evaluating conceptual models and theories.

PMID- 7560530
TI  - Assertiveness.

PMID- 7560531
TI  - Statistics.

PMID- 7560532
TI  - Identifying the characteristics of optimum practice: findings from a survey of
      practice experts in nursing, midwifery and health visiting.
AB  - In a questionnaire survey in England of 1221 practising nurses, midwives and
      health visitors, 18 key characteristics of optimum practice, made up from 77 sub
      item categories, were identified by respondents. Five open-ended questions asked
      respondents to consider various aspects of optimum practice and to comment on
      factors which encouraged those in practice to deliver care of the highest
      quality. Consensus of view was obtained through a Delphi approach. The
      researchers offer commentary on the implications of this research for
      commissioners, providers and the professions and suggest action for those
      concerned with the provision of health care.

PMID- 7560533
TI  - Achieving research-based nursing practice.
AB  - The literature suggests that nurses may be failing to achieve research-based
      practice. A range of reasons why nurses fail to use research findings in practice
      has been highlighted in previous studies. The overall aim of this study was to
      identify the self-perceived research skills needs of trained nurses with the view
      to organizing workshops to meet these needs. Six hundred trained nurses in six
      different health authorities were surveyed using self-administered
      questionnaires. These nurses worked in clinical areas, in hospitals, the
      community and education. The results indicated that 93% (n = 398) of nurses were
      not satisfied with their research skills. Other factors emerging indicated the
      self-perceived skills deficit were those of an elementary nature, including
      locating research reports, reading and evaluating reports and application of
      results to practice, amongst others. This may be an indication of why research
      based practice is still not a reality.

PMID- 7560534
TI  - Critical thinking and intuitive nursing practice.
AB  - In this paper, we analyse how critical thinking and intuitive practice are
      related to expertise in nursing. We examine how intuitive practice, when
      performed automatically without care, vigilance, and criticism, can result in
      prejudice and patterns of practice which are misinformed. We will show that the
      student nurse develops intuitive, skillful performance in nursing by reasoning
      about nursing knowledge and applying reflective, critical thought in practice
      situations, thereby gaining increasing expertise in reasoning as a reliable
      professional ensuring quality client care. The elements of thought necessary for
      sound reasoning in clinical practice will be explored. Finally, we suggest
      educational strategies and tactics which promote the development of the
      intellectual capacities of student nurses as independent critical thinkers.

PMID- 7560535
TI  - Assessing the level of student reflection from reflective journals.
AB  - The concept of reflective learning has been widely adopted in many of the nursing
      curricula today. Reflective learning is of particular relevance to the education
      of professionals, as it encourages students to integrate theory with practice,
      appreciate the world on their own behalf, and turn every experience into a new
      potential learning experience. While nurse educators have widely accepted the
      educational benefits of reflection, research into reflective learning is hampered
      by the lack of reliable and widely accepted methods for assessing whether
      reflection takes place and the level of any reflection. This study attempted to
      develop and test coding systems for written reflective journals based on two well
      known models of reflective thinking. The reflective journals submitted by the
      students were subjected to content analysis at two levels. The findings of this
      study suggest that student writing can be used as evidence for the presence or
      absence of reflective thinking. The process of allocating students to three
      categories of non-reflector, reflector and critical reflector was straightforward
      and reliable. Identifying textual elements within journals and allocating them to
      the finer levels of reflection within a more complex model of reflective thinking
      was, however, more problematic and considerably less reliable.

PMID- 7560536
TI  - The effect of a senior preceptorship on the adaptive competencies of community
      college nursing students.
AB  - A pre-post design was used to examine the effect of a senior preceptorship
      experience on the adaptive competencies, environmental press perceptions and
      learning styles of 55 third-year community college nursing students. Kolb's
      experiential learning theory provided the framework for the study. Subjects rated
      their concrete and abstract competencies and the importance of divergent and
      convergent competencies significantly higher following the preceptorship. They
      also felt that the preceptorship experience contributed significantly more to
      their competency development than their weekly clinical experiences during the
      year. Contrary to expectations, administration of the Learning Style Inventory
      LSI-1976 and LSI-1985 produced inconsistent classifications of subjects' learning
      styles. Implications for nursing are described.

PMID- 7560537
TI  - Neglected conflicts in the discipline of nursing: perceptions of the importance
      and value of practical skill.
AB  - The patient's body has moved out of focus in nursing. This has led to the
      diminishing importance of practical skill in the discipline of nursing. Patients,
      however, consider these skills to be a vital part of good nursing care. How can
      nursing as a practical discipline live with the long-standing conflicts that
      these disparate views create? It is time that theoretical discourse within the
      discipline paid attention to the patient's perception of good nursing care, and
      that efforts are made to investigate how nurses in the clinical setting develop
      and consolidate the practical skills needed for the patient's hygiene, comfort
      and medical treatment. In this paper the conflicts are delineated and conditions
      relevant to their development are discussed.

PMID- 7560538
TI  - Findings of a training needs analysis for qualified nurse practitioners.
AB  - Training needs analyses have been identified as an essential part in the
      development of continuing education programmes and their implementation into
      practice. This study describes the results of a training needs analysis of nurse
      practitioners across three health authorities in England.

PMID- 7560539
TI  - A selective review of the literature on nurse-patient communication: has the
      patient's contribution been neglected?
AB  - The literature on nurse-patient communication is selectively reviewed. Previous
      research has been critical of the quality and quantity of nurse-patient
      communication, describing it as brief and superficial. Nurses are depicted as
      controlling and restricting the course and topics of conversations with patients.
      Communication skills training for nurses has been advocated as a solution for
      this apparent deficit. In this paper it is argued that research has over
      emphasized nurses' roles in nurse-patient communication, particularly their
      communication skills. The patients' contribution to the content and organization
      skills. The patients' contribution to the content and organization of nurse
      patient communication has been largely ignored. Assumptions have been made about
      nurses' and patients' intentions and motives during nurse-patient conversations,
      but the participants, particularly patients, are rarely asked for their views.
      There has been a tendency to view nurse-patient communication in terms of
      isolated excerpts of conversation. When environmental and organizational factors
      are included, it is their effect on nurses' communication capability, not the
      patients', that are the interest. It is suggested that future research consider
      both patients' and nurses' contributions to nurse-patient communication.

PMID- 7560540
TI  - Theoretical and practical considerations on the use of reassurance in the nursing
      management of anxious patients.
AB  - This paper analyses the concept of reassurance in health care, arguing that it
      entails giving information predicting a safe outcome, plus the use of personal
      support to help patients feel secure. The literature on anxiety management
      interventions is reviewed and selected findings are presented from a survey of
      reassurance in nursing practice based on 351 critical incidents reported by 253
      nurses and 51 patients. The survey concludes that reassuring strategies are
      indicated where patients' fears are judged to be unrealistic or excessive.
      Accurate assessment is vital and must take into account coping styles.
      Reassurance may also be indicated as a measure of last resort when working with
      cognitively impaired patients. Personal support interventions are particularly
      valued by hospitalized patients who appear to observe individual nurses in order
      to assess their levels of competence and caring before requesting help.

PMID- 7560541
TI  - Assessment of anxiety in hospital patients.
AB  - There has been research in North America to validate the nursing diagnosis of
      anxiety. As part of this work, Young used the defining characteristics and
      developed a tool to measure anxiety. The present research sought to extend that
      study in the United Kingdom, assess the anxiety-defining characteristics tool and
      identify key indicators of anxiety that might be useful in clinical practice.
      Four anxiety measurement tools, drawn from the literature, were used. These were
      the state trait anxiety inventory, the graphic anxiety scale, the hospital
      anxiety and depression scale, and the anxiety-defining characteristics tool. A
      random sample of 79 hospitalized patients were interviewed and their anxiety
      rated using all four measures. Calculation of Spearman's correlation co
      efficients revealed convergent validity between the anxiety-defining
      characteristics tool and the state trait anxiety inventory and the anxiety score
      on the hospital anxiety and depression scale. Anxiety levels were found not to be
      affected by the age or sex of the respondent, or the length of stay or number of
      previous admissions. Discriminant analysis suggested that six characteristics
      adequately discriminated anxious subjects: sweating, faintness, tendency to blame
      others, continual review of things in their mind, focus on self and a lack of
      self-confidence. The study concluded that there is a scope for further research
      into these characteristics and their use in clinical practice.

PMID- 7560542
TI  - The origins of insane asylums in England during the 19th century: a brief
      sociological review.
AB  - This paper explores the origins of insane asylums in 19th century England by
      comparing the official 'received' medically dominated perspective with an
      alternative sociological perspective. The major structural changes in provision
      are addressed as the focus for analysing the differing histories. A brief review
      is presented of the responses to insane people prior to the national asylum
      programme following the 1845 Lunacy Act, and of the reform logic that underpinned
      asylum care. The alternative sociological perspective presents the origins of
      psychiatric asylums as part of the social and economic changes occurring
      generally at that time. As such the origins of insane asylums are presented as
      part of a state-guided 'sanitary' movement which included poor, criminal and
      insane people within its remit. The effect of state-guided correction was the
      segregation of insane people from both the general population and other deviants
      who were formerly classed together. Insane people are thus presented as a group
      of deviants who departed most radically from the 'rational individualist'
      qualities of self-control, predictability and responsibility required in the
      industrialized world of capital social relations that emerged during the last
      century.

PMID- 7560543
TI  - Food craving during the menstrual cycle and its relationship to stress, happiness
      of relationship and depression; a preliminary enquiry.
AB  - The associations between retrospective ratings of food craving and depression
      during the premenstrual, menstrual and postmenstrual phases of the preceding
      menstrual cycle and ratings of current levels of stress and happiness of
      relationship were examined in 5,546 women. In each phase examined, the severity
      of food craving was very strongly related to the reported severity of depression.
      Overall levels of food craving were inversely related to happiness of
      relationship and there was some interaction of this effect with on-going stress.
      However, once the effect of depression was accounted for there was no effect of
      either current stress or happiness of relationship on the cycle-related pattern
      of food craving and in general the magnitude of the effect of these psychosocial
      variables was very small compared with that of depression. Food cravings were
      also reported in the absence of depression, tending to show a cycle-related
      pattern, maximal premenstrually, declining during menstruation and further
      postmenstrually. Whilst this is consistent with a cycle-related biological
      explanation, it remains unclear whether the striking amplification of food
      craving ratings in association with co-existing depression, in all three phases
      examined, is also biologically based or dependent on psychological mechanisms. In
      view of the retrospective nature of the ratings of mood and craving and the
      limited assessment of stress and happiness of relationship, these findings should
      be regarded as preliminary. They are, however, of potential importance and the
      association between these two common phenomena deserves further study.

PMID- 7560544
TI  - A double-blind placebo-controlled study of Org 3770 in depressed outpatients.
AB  - 90 patients between 18 and 65 years, with a DSM-III diagnosis of moderate or
      severe major depressive episode, were randomized to 6 weeks of treatment with Org
      3770 or placebo in a double-blind trial. On main efficacy parameters, the 17-item
      HAMD, MADRS and CGI, Org 3770 was significantly superior to placebo (P < or =
      0.05) in weeks 1-4 and at endpoint and recommended as continuation treatment to
      significantly more patients. The tolerability of Org 3770 was good: the only
      significant differences as compared with placebo were in the incidences of
      somnolence and increased appetite. The results show that Org 3770 is an effective
      and well-tolerated drug for the treatment of major depressive disorder.

PMID- 7560545
TI  - Major depression and the risk of attempted suicide.
AB  - We examined the risk of attempted suicide in 100 inpatients during a major
      depressive episode. We hypothesized that patients who attempt suicide have a
      vulnerability for suicidal behavior independent of severity or duration of
      depression, manifested by suicide attempts early in the course of a depressive
      episode. The first 3 months after the onset of an MDE and the first 5 years after
      the lifetime onset of major depressive disorder represented the highest-risk
      period for attempted suicide, independent of the severity or duration of
      depression. Familial, genetic, early-life loss experiences and comorbid
      alcoholism may be causal factors.

PMID- 7560546
TI  - A 3-year follow-up of a group of treatment-resistant depressed patients with a
      MAOI/tricyclic combination.
AB  - Treatment-resistant depression is a clinical complication that not infrequently
      affects a certain number of patients. Within the treatment strategies proposed
      for this condition, the association of a MAO inhibitor (MAOI) with a tricyclic
      antidepressant has gained reputation both for its unusual efficacy, as for its
      potential toxicity. However, when cautions are taken, it may be safely
      administered. Most reports on this combination have been carried in nonresistant
      patients and, when resistant patients are included, only the acute phase of the
      treatment is reported. In this study, a group of well-defined resistant patients
      received an open trial with the association of isocarboxazide and amitryptiline
      (n = 25). Those who responded were followed during the next 3 years (n = 12) and
      every 6 months an attempt was made to discontinue the MAOI and continue only with
      amitryptiline. At the end of the study, 4 patients maintained response with
      single medication, 6 still required both drugs and 2 relapsed. No clinical
      differences were apparent between the outcome groups, except that those who
      maintained their response only with the 2 combined drugs had more previous
      depressive episodes than the others. The isocarboxazide/amitryptiline combination
      may be a good treatment option for at least some forms of resistant depression.
      The safety of this treatment modality is confirmed, even when given for long
      periods of time. The study also suggest that there are no clinical
      characteristics in resistant depression that may predict the treatment outcome
      but, perhaps in some patients, a combined treatment is required to obtain a
      broader biochemical effect that could convert them from nonresponders to
      responders.

PMID- 7560547
TI  - Suicidal ideas during premenstrual phase.
AB  - The aim of the present study was to determine the frequency of suicidal ideas and
      death wish among 296 women from urban, rural, industrial and college populations.
      Suicidal ideas and/or death wish during premenstrual period were reported by 30
      (10%) subjects, more so among college students and industrial working women and
      less among housewives. Premenstrual symptoms, like depression, irritability, mood
      swings, sense of losing control and water retention, were significantly more
      often reported by women who had suicidal ideas as compared with women without
      suicidal ideas.

PMID- 7560548
TI  - Relationship between erythrocyte magnesium, plasma electrolytes and cortisol, and
      intensity of symptoms in major depressed patients.
AB  - 53 male and female drug-free major depressed patients were separated into three
      groups according to the severity of the depression. In the entire regrouped
      population, plasma and erythrocyte magnesium (Mg) were shown to increase as
      compared with 48 healthy controls, confirming our previous studies. The middle
      and highly depressed patients had higher erythrocyte and also plasma Mg levels
      than either lowly depressed patients or controls. Only, a few differences were
      noticed in plasma sodium, potassium and calcium (Ca) in the three groups of
      patients, except for ultrafiltrable plasma Ca, measured for the first time in
      affective disorders. Thus, erythrocyte and also plasma Mg are shown to be
      associated with the intensity of the depression. As blood hypomagnaesemia is
      often related to hyperexcitability, further investigations are actually in
      process to shown whether hypermagnesaemia might be, in contrast, associated with
      psychomotor retardation as observed in many depressed patients.

PMID- 7560550
TI  - Sensation-seeking and emotional disturbances in depression: relationships and
      evolution.
AB  - The French abbreviated form of the sensation-seeking scale was given to 183
      hospitalized depressed subjects meeting the DSM-III-R criteria for major
      depression. Depressed subjects, men and women, scored significantly lower than
      controls from the general population, paired as to age and sex, on all of the
      subscales. There was no relationship to the intensity of depression and anxiety.
      Relationships between emotional disturbances and sensation-seeking were
      differentiated according to the specificity of each subscale and to age and sex.
      There was no significant difference between baseline and after-treatment
      sensation-seeking scores and subjects at discharge still scored significantly
      lower than controls. Hypotheses on evolution at a later date after the
      hospitalization are made. The finding of positive relationships for some subjects
      between sensation-seeking and anhedonia is interpreted in regard to a
      compensatory process.

PMID- 7560549
TI  - The hypothalamic-pituitary-thyroid axis in patients maintained on lithium
      prophylaxis for years: high triiodothyronine serum concentrations are correlated
      to the prophylactic efficacy.
AB  - Serum concentrations of thyrotropine (TSH), thyroxine (T4), free T4 (fT4),
      triiodothyronine (T3) and reverse T3 (rT3) were measured 4 x during a 12-month
      period in 28 patients with major depressive disorder maintained on lithium
      prophylaxis for 4-23 years (mean = 11.8). The course of illness was carefully
      monitored and documented for all patients throughout a 3.5-year period. All
      hormones were also measured in 41 healthy controls matched for age and gender.
      Patients on lithium had normal serum concentrations of TSH, T4, fT4 and T3 only
      the levels of rT3 were elevated. The efficacy of the lithium prophylaxis was
      significantly correlated to the serum concentrations of T3, i.e., the higher the
      patients' serum levels of T3, the shorter was the overall duration of recurrences
      of depression within the 3.5-year period. We conclude that: (1) thyrotropine and
      the thyroid hormones, which are often abnormal during the first weeks or months
      of lithium treatment, returned to normal when lithium prophylaxis was maintained
      for years; (2) a possible explanation for the higher T3-serum concentrations in
      responders might be that lithium interacts with thyroid hormone metabolism in the
      CNS, leading to enhanced T3 concentrations in the tissue and to a secondary
      increase in the serum concentrations of T3.

PMID- 7560551
TI  - Affective valence of words, explicit and implicit memory in clinical depression.
AB  - Explicit and implicit memory for affectively valenced words (positive, negative
      or neutral) were investigated in 30 patients suffering from a major depressive
      episode (DSM-III-R criteria) and 30 normal control subjects. Explicit memory was
      assessed with a free-recall and a recognition task and implicit memory with a
      word-stem completion task. Depressed and control subjects recalled more
      emotional, i.e., positive and negative, words than neutral ones. They recognized
      less negative than neutral words. In contrast, to recall and recognition
      performance, word-completion performance was not sensitive to the affective
      valence of words: depressed and control subjects exhibited equivalent priming of
      positive, negative and neutral words. These results indicate that, in depressed
      and normal subjects, the affective valence of words influences memory when
      conscious, intentional recollection is required but is devoid of effect when such
      a recollection is not required.

PMID- 7560552
TI  - Suicidal behavior in patients with panic disorder: retrospective and prospective
      data.
AB  - This paper examines factors associated with suicidal behavior in patients with
      anxiety disorders. HARP is a naturalistic, prospective, longitudinal follow-up
      study. This paper examines 527 subjects with panic disorder (with or without
      agoraphobia). 9% of the subjects reported past suicidal behavior. Factors
      associated with suicidal behavior were depressive disorders, substance abuse,
      eating disorders, PTSD and personality disorders as well as having early onset of
      the first anxiety or depressive disorder. Subjects had a 4.5% P of suicidal
      behavior during the first 30 months of follow-up. All prospectively recorded
      suicidal behavior occurred in subjects with depressive disorders. In these panic
      disorder patients, suicidal behavior rarely occurred in the absence of affective
      disorders. Certain nondepressive disorders also substantially increased the risks
      of suicide attempts/gestures.

PMID- 7560553
TI  - Is diurnal variation of mood associated with parasympathetic activity?
AB  - 18 patients with distinct improvement of mood in the evening and 18 patients
      without, both suffering from major depression and equally treated with tricyclic
      antidepressants (TCA), and an age- and sex-matched group of 18 normal control
      subjects underwent a standardized heart-rate (HR) analysis (HRA) in the morning
      (08:00) and 12 h later in the evening (20:00). The battery of cardiovascular
      reflex tests included the determination of HR variability (HRV) while resting and
      during deep breathing, and a spectral HRA. The depressed patients with diurnal
      variation of mood showed significantly decreased HR and significantly increased
      HRV parameters while resting and during deep respiration in the evening. On the
      contrary, patients without diurnal changes of mood just showed a significant HRV
      increase during deep respiration in the evening. No statistically significant
      changes of these parameters were detected in the healthy subjects. It is not
      known if the observed changes of HR parameters representing increment of
      parasympathetic tone are intrinsically related to the mood swings or if this
      rhythm just becomes visible under the circumstances of depression. Also, the
      impact of TCA treatment upon the results remains to be elucidated.

PMID- 7560554
TI  - Deficient inhibitory control in attention deficit hyperactivity disorder.
AB  - The purpose of this study was to examine two executive control processes-
      response inhibition and re-engagement of responses after inhibition in children
      with attention deficit hyperactivity disorder (ADHD). Thirty-three children with
      ADHD and 22 normal control children of similar age (7 to 11 years) and mean IQ
      (107) were tested with the change paradigm. ADHD subgroups were defined by the
      context in which the ADHD symptoms predominated (in the home only; at school
      only; and in both, i.e., pervasive ADHD). Children with marked oppositional
      defiant or conduct disorder were excluded. Children with ADHD exhibited deficits
      in inhibitory control and in response re-engagement. Deficits were greatest in
      pervasive ADHD and, to a lesser extent, in those with ADHD limited to the school
      context. ADHD limited to the home context showed the least deficit. These results
      replicate an earlier study that found deficient inhibitory control in pervasive
      ADHD and demonstrate that the deficit in ADHD involves a second aspect of
      executive control.

PMID- 7560555
TI  - Perceptions of fear in other children and adolescents: the role of gender and
      friendship status.
AB  - Gender differences in fear were examined in 693 Chinese children and adolescents.
      Subjects were asked to rate their own fears, the fears of their best friends, and
      the fears of "other" classmates using the Fear Survey Schedule for Children-
      Revised (Ollendick, 1983). Consistent with previous investigations in Western and
      Eastern countries, girls rated themselves as more fearful than boys. In addition,
      both girls and boys rated their best friends as similar in number, content, and
      intensity of fears. However, girls rated their classmates as less fearful than
      themselves or their best friends, while boys rated their classmates as more
      fearful then themselves or their best friends. Findings are discussed in terms of
      gender role expectations and similarity-attraction hypotheses.

PMID- 7560556
TI  - External validation of oppositional disorder and attention deficit disorder with
      hyperactivity.
AB  - Validity of the distinction between oppositional disorder (OD) and attention
      deficit disorder with hyperactivity (ADDH) was examined in a sample of 6- to 12
      year-old boys with behavior problems. Problem identification,
      cognitive/attentional, family context, and behavioral symptom differences were
      examined among nine boys with OD only, 20 with ADDH, 40 with comorbid OD and
      ADDH, and 28 with neither disruptive behavior disorder. Systematic comparisons of
      groups including and excluding the OD and ADDH diagnoses were undertaken to
      determine the existence of pure OD and pure ADDH disorder effects. The most
      consistent result was the lack of evidence for either pure OD or pure ADDH
      effects. Most of the significant findings reflected differences between the
      nondisruptive (neither) and comorbid groups. The results support the importance
      of comorbidity, but they provide little support for disorder-specific
      distinctions between oppositional and attention deficit disorders.

PMID- 7560557
TI  - Social problem solving: a moderator of the relation between negative life stress
      and depression symptoms in children.
AB  - The social problem-solving skill of generating effective alternative solutions
      was tested as a moderator of the relation between negative life stress and
      depressed mood in children. Boys (n = 25) and girls (n = 25), ages 8 to 12 years,
      from inner-city, lower socioeconomic group families, completed measures of
      depression symptoms, negative impact of life events, and quantity and
      effectiveness of alternative solutions to social problems. Results indicated that
      the effectiveness of alternative solutions children generate in response to peer
      social problems moderates the relation between stress and depression. Children
      who experienced a high impact of negative life events, with less effective social
      problem-solving skills, reported higher levels of depression compared to children
      who experienced a high impact of negative life events but exhibited more
      effective social problem-solving skills. Results are discussed in terms of
      alternative theoretical models for the mechanisms whereby effective social
      problem-solving skills moderate stress-related depression.

PMID- 7560558
TI  - Clinic referral for oppositional defiant disorder: relative significance of
      attachment and behavioral variables.
AB  - Attachment classifications have been found to distinguish clinic-referred,
      oppositional preschool boys from controls, but there has been no previous effort
      to examine the relative contribution of attachment when behaviors from a social
      learning perspective are also considered. The present study examined the
      contribution of attachment and behavioral variables to the prediction of clinic
      referral for oppositional defiant disorder in a sample of preschool boys. We
      hypothesized that the attachment measures would offer better discrimination of
      clinic and control group boys at this age. This hypothesis was confirmed when the
      attachment measures were compared with the parent-child behaviors most strongly
      associated with social learning conceptualizations of disruptive problems
      (maternal commands and criticism, and child noncompliance), but rejected in a
      more stringent test in which the attachment measures were compared with the
      behavioral variables distinguishing the groups in this particular sample.

PMID- 7560559
TI  - A behavioral assessment scale for attention deficit disorder in Brazilian
      children based on DSM-IIIR criteria.
AB  - A teacher scale based on DSM-III-R diagnostic criteria for attention deficit
      hyperactivity disorder (ADHD) was developed for the behavioral assessment of
      children in Brazil. A total of 2,082 children (782 males and 1,300 females) with
      a mean age of 11.2 years who were attending a public school in the greater Rio de
      Janeiro area were the subjects of this study. Two factors (Hyperactivity
      Impulsivity and Inattention) were extracted from a principal-factor analysis
      conducted on the data, and the factor structure of the scale was found to be
      stable. Ratings of boys were higher than ratings of girls, and younger children
      had higher ratings than older children for both factors. Test-retest reliability
      for each item of the scale ranged from .56 to .70. The data are discussed in view
      of current controversies in the factor structure of teacher ratings of DSM-III-R
      ADHD symptoms.

PMID- 7560560
TI  - Community-based multiple-gate screening of children at risk for conduct disorder.
AB  - The present study employed a multiple-gate screening procedure to identify
      children at risk for the development of conduct disorder. Measures of cross
      setting disruptive behavior and parent discipline practices were administered in
      sequential fashion to screen a population of 7,231 children attending suburban
      elementary schools. Convergent validity of the respective gating measures was
      confirmed by significant correlations with adjustment constructs. Analyses of
      covariance performed between positive screens, negative screens, and low-risk
      comparison children on adjustment constructs at each gate supported the
      discriminative validity of the gating procedure. Hierarchical regression analyses
      demonstrated that the gating measures were predictive of diagnostic ratings of
      attention deficit hyperactivity disorder and oppositional defiant disorder that
      were obtained 18 months following the screening. A stepwise logistic regression
      analysis indicated that the best predictors of high-risk group membership were
      variables related to family process, including poor family communication and
      involvement, poor maternal coping skills, and an external parent locus of
      control.

PMID- 7560561
TI  - Abusive legislation.

PMID- 7560563
TI  - Relining, rebasing dentures.

PMID- 7560562
TI  - Thermafil takes issue.

PMID- 7560564
TI  - Periodontitis-causing pathogens detected in HIV-positive children, siblings.

PMID- 7560565
TI  - FDA oks latex allergy test.

PMID- 7560566
TI  - Genetic research resource established.

PMID- 7560567
TI  - Smoking and its effects on early-onset periodontitis.
AB  - The findings of a recent study show that smoking was more prevalent in a group of
      patients with generalized early-onset periodontitis and adult periodontitis than
      in patients with localized juvenile periodontitis or healthy periodontium. In
      patients with generalized early-onset periodontitis, smoking had a significant
      effect on periodontal attachment loss; these patients had significantly more
      teeth with affected sites and a greater mean loss of attachment than patients who
      did not smoke. Thus, the risk of smoking could greatly accelerate tooth loss in
      this relatively young group of individuals who are already at high risk for
      progressive periodontal attachment loss.

PMID- 7560568
TI  - Smokeless tobacco use: how it affects the performance of major league baseball
      players.
AB  - The authors examined the effect of smokeless tobacco use on the athletic
      performance of major league baseball players during the 1988 season. They
      evaluated performance records of 158 players on seven major league teams who
      played or pitched at least 10 games or innings during the 1988 season. ST use,
      they concluded, is not related to player performance in major league baseball but
      does place players at significantly increased risk for mucosal lesions and other
      oral pathology.

PMID- 7560569
TI  - Applying composite luting agent ultrasonically: a successful alternative.
AB  - The authors conducted research to determine if sonic vibration affected the
      viscosity of a composite luting agent. They found that using either an ultrasonic
      or a sonic scaler can thin composite resin. The thickness of the lute is similar
      to that resulting from manual loading methods, but it is obtained in much shorter
      time periods and with lower loads.

PMID- 7560570
TI  - How occlusal forces change in implant patients: a clinical research report.
AB  - The author recorded the occlusion of 100 patients with fixed implant prostheses
      on 571 endosseous root form implants when the implants were placed. He made six
      subsequent occlusal contact comparisons at three-month intervals. Hyperocclusion
      occurred on implant prostheses in nearly half of the patients during the test
      period, with the majority of changes occurring in the first three to six months.
      These changes in the distribution of occlusal contact forces may partially
      explain the reports of early implant failure by other investigators, and they
      suggest the need for a more vigorous post-insertion occlusal evaluation.

PMID- 7560571
TI  - Practice parameters in dentistry: where do we stand?
AB  - Practice parameters or guidelines have been touted as a means of enhancing
      clinical decision making. The authors surveyed dental organizations and reviewed
      the literature to determine the availability of parameters for dental conditions.
      An Institute of Medicine report has suggested that for parameters to provide the
      desired benefits, they must meet certain criteria and possess certain
      characteristics. Using these criteria, the authors assess available parameters in
      dentistry.

PMID- 7560572
TI  - Preventing post-treatment bacteremia: comparing topical povidone-iodine and
      chlorhexidine.
AB  - It is well known that the occurrence of bacteremia after dental procedures can
      place certain patients at risk for bacterial endocarditis. The authors compared
      the efficacy of two antiseptic agents in the prevention of post-treatment
      bacteremia in 120 dental patients. Before treatment, dentists irrigated the
      gingival sulcus of each patient with 10 percent povidone-iodine, 0.2 percent
      chlorhexidine or sterile water. The authors report lower levels of bacteremia
      among patients treated with the povidone-iodine solution.

PMID- 7560573
TI  - Nerve damage associated with inferior alveolar nerve blocks.
AB  - The authors reviewed 12 cases in which altered sensation occurred in the
      distribution of the inferior alveolar or lingual nerves following injection of a
      local anesthetic for restorative treatment only. Most patients suffered only
      partial damage, but recovery was poor. The exact mechanism of the nerve damage is
      unknown, but a number of theories are proposed. The extent of this problem is
      also unknown, but many more cases probably exist than have been reported to date.

PMID- 7560574
TI  - Using anticipatory guidance to provide early dental intervention.
AB  - While the infectious-disease model continues to dominate the design of preventive
      programs for children, ample evidence supports the need to consider other aspects
      of caries prevention such as functional and developmental considerations--and to
      do it earlier than conventional wisdom would suggest--if further gains are to be
      made in caries reduction. Anticipatory guidance provides a framework for
      prevention that goes beyond caries to address all aspects of children's oral
      health.

PMID- 7560575
TI  - Restorative dentistry: an update for practitioners, educators, examining boards.

PMID- 7560576
TI  - Legal issues affecting dentistry's role in preventing child abuse and neglect.
AB  - Dentists can best help protect children from maltreatment through an
      understanding of the child protective services process. All dentists are covered
      under state statutes as mandated reporters of suspected child abuse and neglect.
      Reporting statutes vary considerably from state to state. All dentists must
      understand the intricacies of applicable state laws to help identify suspected
      child maltreatment while protecting themselves from liability.

PMID- 7560577
TI  - Invest now for the future.

PMID- 7560578
TI  - Dental erosion.

PMID- 7560579
TI  - Dental implants.

PMID- 7560580
TI  - Smoking triggers cleft palate development.

PMID- 7560581
TI  - Cinnamon linked to oral sores, irritation.

PMID- 7560582
TI  - Percutaneous injuries in practicing dentists. A prospective study using a 20-day
      diary.
AB  - A novel diary study of 2,304 practicing U.S. dentists examined the frequency and
      nature of percutaneous injuries over one dentist-month. Burs were responsible for
      most extraoral injuries (40 percent), and syringe needles accounted for most
      intraoral injuries (32 percent). The annualized mean injury rate was 3.35, which
      represents about a threefold decrease since 1987.

PMID- 7560583
TI  - Percutaneous exposures to HIV-infected blood. Among dental workers enrolled in
      the CDC Needlestick Study.
AB  - The authors found that 19 percutaneous exposures among dental workers occurred
      both during and after use of instruments such as syringe needles and scalers.
      Specific information about the device and action associated with an exposure is
      important for prevention efforts, including safer instruments and work practices.
      Most of these exposures probably involved smaller, rather than larger, amounts of
      blood infected with the human immunodeficiency virus. To our knowledge, none of
      the exposures resulted in HIV transmission to an enrolled dental worker.

PMID- 7560584
TI  - A clinical evaluation of a resin-modified. Glass ionomer restorative material.
AB  - Compomers, resin-modified glass ionomers, were developed to improve the physical
      properties and clinical handling of glass ionomers. Compomers can be designed to
      be light-activated and used as restoratives or liners. This article reports data
      collected up to 12 months after placement of both compomer restorations and
      liners and is part of an ongoing study evaluating the performance of this
      material. Based on this data, the authors conclude that this new generation of
      light-activated glass-ionomer restoratives provides clinical results comparable
      to those recorded for composite resins at 12 months.

PMID- 7560585
TI  - Contribution of biofilm bacteria to the contamination of the dental unit water
      supply.
AB  - The authors studied the contribution of bacterial biofilm to the contamination of
      the dental unit water supply, as well as the effects of flushing and sodium
      hypochlorite treatment on reducing the number of contaminants. This study
      demonstrated that biofilm in the dental tubing was the primary source of
      contaminated water delivered by dental units.

PMID- 7560586
TI  - Differential diagnosis of jaw pain in the elderly.
AB  - While many diseases are marked by pain in the mandible or maxilla, a number of
      these conditions appear to be more prevalent in people 65 years and older. People
      in this age group often have a number of medical problems and take a variety of
      medications, so clear-cut diagnosis of jaw pain can be difficult. Memory deficits
      or concomitant somatic complaints can further complicate the diagnosis. This
      article presents a differential for jaw pain in the elderly and reports on a
      pertinent case.

PMID- 7560587
TI  - The use of pulse oximetry in dentistry.
AB  - Hypoxia in the dental setting, especially in medically compromised or sedated
      patients, is a common perioperative problem. It is essential that clinicians
      monitor patients' vital signs during certain dental procedures to ensure optimal
      patient safety. This article describes the principles and use of pulse oximetry
      to help prevent hypoxia in dental patients.

PMID- 7560588
TI  - Clinical guidelines for photocuring restorative resins.
AB  - Success in using light-cured resin composites relies heavily on proper curing
      time and intensity. Because these factors are so critical, the authors reviewed
      the literature to arrive at guidelines for optimal curing conditions. The
      guidelines emphasize maintenance of the curing lights, consideration of the type
      of restorative material used and duration of exposure.

PMID- 7560589
TI  - Surgically treating a benign cementoblastoma while retaining the involved tooth.
AB  - The authors describe the case of a patient who had tenderness when biting and
      mild sensitivity to palpation as well as a radiopaque lesion attached to the
      mesial root of a mandibular first molar. Evidence pointed to a benign
      cementoblastoma. The dentist redid the original endodontic treatment and
      surgically removed the lesion, leaving the involved tooth intact. The authors
      suggest that in certain cases, it may be possible to remove benign
      cementoblastomas affecting molars without extracting the involved teeth.

PMID- 7560590
TI  - Increasing patient service by effective use of dental hygienists.
AB  - Dental hygienists are well-educated professionals. Their responsibilities
      generally have been limited to scaling and polishing. Expanding into other
      clinical techniques, as permitted by practice laws, provides diversity for
      hygienists, lower cost services for patients and more time for dentists to
      provide the services their extra education allows.

PMID- 7560591
TI  - Computer-assisted fabrication of orthodontic appliances: considering the
      possibilities.
AB  - The authors describe a computer-controlled system that can partially automate the
      fabrication of maxillary orthodontic appliances. The system can be programmed to
      deposit and cure the acrylic portion of these appliances. Using this new process,
      the operator places the orthodontic wires and expansion screws on the surface of
      the dental cast, secures the cast onto the machine and describes the desired
      shape of the appliance via graphical user interface. The machine then applies and
      cures the acrylic to form the finished appliance. Only minimal grinding and
      buffing is required.

PMID- 7560592
TI  - Efficacy and proarrhythmia of oral sotalol in pediatric patients.
AB  - OBJECTIVES: This study sought to assess the efficacy of oral sotalol for various
      arrhythmias in pediatric patients and to evaluate the incidence of proarrhythmia
      and systemic side effects. BACKGROUND: Sotalol is a beta-adrenergic blocking
      agent with additional class III antiarrhythmic properties. Experience in
      pediatric patients is limited. Data concerning the incidence of proarrhythmia in
      children are lacking. METHODS: Seventy-one pediatric patients (mean age 7.3
      years) with various supraventricular and ventricular tachyarrhythmias were
      treated with oral sotalol. All the patients were admitted to the hospital for
      initiation of sotalol therapy. Antiarrhythmic and proarrhythmic effects of
      sotalol were assessed by daily surface electrocardiograms (ECGs) during the in
      hospital phase and by serial Holter monitoring. RESULTS: Sotalol was either
      completely (27 [66%] of 41 patients) or partially effective (11 [27%] of 41) in
      38 (93%) of 41 patients with supraventricular reentrant tachycardias. In patients
      with atrial flutter predominantly after operation for congenital heart disease,
      sotalol was effective in 84% of patients (completely in 9 of 19 and partially in
      7 of 19). Ventricular tachycardia was completely (3 of 11) or partially (4 of 11)
      controlled in 64% of children. Proarrhythmia occurred in seven patients (10%) and
      consisted of symptomatic bradycardia from sinoatrial block and high grade
      atrioventricular (AV) block, respectively, in two children; asymptomatic high
      grade AV block in one; torsade de pointes in one; and relevant increased
      ventricular ectopic activity in three. Proarrhythmia required drug
      discontinuation in four patients. Mean duration of treatment for all patients was
      18 months (range 1 to 40). CONCLUSIONS: Sotalol was an effective antiarrhythmic
      drug for a wide range of pediatric tachyarrhythmias. The considerable number of
      patients with proarrhythmic effects indicates the need for initiation of
      treatment on an inpatient basis and close monitoring by serial Holter
      electrocardiography.

PMID- 7560593
TI  - Early changes in ventricular septal defect size and ventricular geometry in the
      single left ventricle after volume-unloading surgery.
AB  - OBJECTIVES: This study investigated the phenomenon of, and the relation between,
      alterations in ventricular geometry after acute surgical volume unloading of the
      ventricle and the development of subaortic stenosis in patients with a single
      ventricle and ventricular septal defect-dependent systemic flow. BACKGROUND:
      Subaortic outflow obstruction has been observed to occur in patients with a
      single left ventricle after placement of a pulmonary artery band. The timing and
      etiology of this phenomenon are not well defined. METHODS: The preoperative and
      postoperative echocardiograms of 18 patients 14.9 +/- 22.8 months old (mean +/-
      SD) with a diagnosis of single left ventricle who underwent pulmonary artery
      banding or cavopulmonary connection were reviewed. Postoperative studies were
      performed a mean of 7.0 +/- 6.5 days after operation. The ventricular septal
      defect diameter was measured in two orthogonal views and the area calculated
      using the formula for an ellipse. Interventricular septal and posterior wall
      thickness and left ventricular diameter and length were also measured. RESULTS:
      Mean ventricular septal defect area indexed to body surface area diminished by 36
      +/- 23% (3.1 +/- 2.7 to 2.0 +/- 1.8 cm2/m2, p < 0.01). Mean interventricular
      septal and posterior wall thickness increased significantly, and left ventricular
      diameter and length decreased significantly. A greater diminution in ventricular
      septal defect area was noted after cavopulmonary connection (41 +/- 19%, p <
      0.01) than after pulmonary artery banding (25 +/- 28%, p = 0.22). CONCLUSIONS: In
      the single left ventricle, diminution in ventricular septal defect size occurs
      early and is related to an acute alteration in ventricular geometry that
      accompanies the decrease in ventricular volume. Ventricular septal defect
      diminution was greater after volume unloading of the ventricle after
      cavopulmonary connection than after pulmonary artery banding.

PMID- 7560594
TI  - Cardiopulmonary function in adult patients late after Fontan repair.
AB  - OBJECTIVES: The clinical status and exercise assessment of adult patients late
      after the Fontan operation were reviewed to determine cardiovascular function.
      BACKGROUND: The Fontan operation is the final operation for many patients with
      tricuspid atresia or a single ventricle. Follow-up reports describe most patients
      to be in Canadian Cardiovascular Society functional class I or II. Objective
      measures of cardiac performance in the pediatric age group have shown significant
      dysfunction. METHODS: Forty-seven adult patients were seen late after the Fontan
      operation at the Toronto Congenital Cardiac Centre for Adults. Thirty of these
      underwent cycle ergometry to determine maximal exercise capacity. Maximal
      ventilation, maximal oxygen uptake and anaerobic threshold were determined from a
      ramp exercise protocol. Ejection fraction at rest and during exercise was
      measured with gated radionuclide angiography. Results were compared with those of
      eight normal volunteers. Results are given as mean +/- SD. RESULTS: Thirty
      patients underwent cardiopulmonary exercise testing 6.7 +/- 3.9 years after a
      first Fontan operation. Clinically 93% were in functional class I or II. The
      Fontan group patients had a significantly lower maximal work load (548 +/- 171
      vs. 1,094 +/- 190 kilopond-meters, p < 0.00001), anaerobic threshold (11.2 +/-
      2.9 vs. 23.6 +/- 4.6 ml/kg per min) and maximal oxygen consumption (14.8 +/- 4.5
      vs. 42.1 +/- 10.0 ml/kg per min). Systemic ventricular ejection fraction was
      lower at rest (38 +/- 12% vs. 58 +/- 7%) and during exercise (40 +/- 15% vs. 70
      +/- 8%). CONCLUSIONS: Despite a clinical impression of good function, by
      objective measures adult patients continue to have significant cardiovascular
      limitation late after the Fontan operation.

PMID- 7560595
TI  - Improved electrocardiographic detection of echocardiographic left ventricular
      hypertrophy: results of a correlated data base approach.
AB  - OBJECTIVES: We used electrocardiographic (ECG) and echocardiographic measurements
      from 3,351 adults from the Framingham Heart Study to evaluate the performance of
      10 ECG criteria in detecting left ventricular hypertrophy before and after
      adjustment for gender, age and obesity. BACKGROUND: Significant improvement in
      the sensitivity and specificity of ECG voltage-based criteria for detection of
      echocardiographic left ventricular hypertrophy using gender-specific criteria
      adjusted for age and obesity has been demonstrated. METHODS: Gender-specific
      correlation and regression analyses were used to identify the five most sensitive
      ECG criteria and to adjust them for age and obesity. Standard and truncated
      receiver operating characteristic curves were used to compare the selected
      criteria. RESULTS: Linear regression of left ventricular mass on ECG voltages,
      body mass index and age yielded considerably stronger relations for women than
      for men because of the greater correlation between ventricular mass and body mass
      index in women. Obesity and age adjustment of the five voltage criteria produced
      considerable improvement in their performance. The voltage sum of the R wave in
      lead aVL and the S wave in lead V3, alone and in combination with QRS duration,
      had a sensitivity at 95% specificity of 32% and 39%, respectively, in men and 46%
      and 51%, respectively, in women after adjustment. Tables of critical voltages for
      the adjusted criteria and representative performance values are presented.
      CONCLUSIONS: Incorporation of obesity and age in ECG algorithms consistently
      improves their performance in the detection of hypertrophy. The development of
      such criteria will enhance the utility of this inexpensive screening test. Such
      ECG approaches should be used in clinical trials to assess the efficacy of
      antihypertensive treatment to effect regression of left ventricular hypertrophy.
      A search for further improvements in the efficacy of ECG criteria for this
      purpose is warranted. Independent validation of this approach is needed.

PMID- 7560596
TI  - Identification of patent foramen ovale permitting paradoxic embolism.
AB  - OBJECTIVES: We sought to analyze the morphologic and functional characteristics
      of the patent foramen ovale in patients with different clinical likelihoods for
      paradoxic embolism. BACKGROUND: The incidence of patent foramen ovale is
      increased in patients with otherwise unexplained arterial ischemic events.
      Because signs of venous thrombosis are absent in most patients, the diagnosis of
      paradoxic embolism is often questioned, even when patent foramen ovale is the
      only potential explanation for the ischemic event. METHODS: Seventy-eight
      patients with a patent foramen ovale detected by contrast transesophageal
      echocardiography were studied: 21 patients with an otherwise unexplained arterial
      ischemic event and clinical evidence implying paradoxic embolism (group I), 30
      patients with an unexplained ischemic event but no clinical evidence for
      paradoxic embolism (group II) and 27 patients without an ischemic event (group
      III). RESULTS: During transesophageal contrast echocardiography, patients in
      group I had more severe right to left shunting (mean +/- SD 52 +/- 16% of the
      left atrial area filled with contrast medium) and a wider opening of the patent
      foramen ovale (7.1 +/- 3.6-mm separation between the septum primum and the septum
      secundum) than did patients in group II (35 +/- 15% and 4.4 +/- 3.2 mm,
      respectively, p < 0.001) or group III (23 +/- 12% and 3.0 +/- 2.0 mm,
      respectively, p < 0.001). The incidence of atrial septal aneurysm was similar in
      the three groups. Severe contrast shunting (> or = 50% of the left atrial area
      filled with contrast medium) and wide opening of the patent foramen ovale (> or =
      5-mm separation) revealed a high sensitivity (71% and 86%, respectively) and high
      specificity (86% and 96%, respectively) for identification of group I patients.
      CONCLUSIONS: Right to left contrast shunting is more severe and opening of the
      patent foramen ovale is larger in patients with ischemic arterial events
      considered to be due to paradoxic embolism. In patients with a patent foramen
      ovale as the only potential cause for ischemic events and no signs of venous
      thrombosis, morphologic and functional variables assessed by transesophageal
      echocardiography may be helpful in estimating the likelihood of paradoxic
      embolism.

PMID- 7560597
TI  - Gender-specific reference M-mode values in adults: population-derived values with
      consideration of the impact of height.
AB  - OBJECTIVES: The purpose of this investigation was to derive population-based
      reference values for M-mode echocardiographic dimensions that can be applied in
      epidemiologic studies, clinical trials and clinical practice and to determine
      optimal methods for adjusting these dimensions for body size. BACKGROUND: M-mode
      echocardiography remains an important modality for studying cardiovascular
      disease; this is especially true with regard to detecting target organ damage in
      systemic hypertension. Most previously published reference values were derived
      from hospital-based series or relatively small samples and were not gender
      specific. METHODS: Using a sample of 288 men and 524 women who were between 20
      and 45 years of age and who were free of cardiovascular disease, reference values
      were derived for end-diastolic and end-systolic left ventricular internal
      dimensions, left ventricular wall thickness and left atrial dimension. The
      relations between these dimensions and height, a measure of body size relatively
      independent of obesity, were investigated using various regression models.
      RESULTS: Nomograms for mean and 95th percentile values in men and women were
      constructed on the basis of linear regression models relating echocardiographic
      dimensions to height. Adjustment for body surface area greatly attenuated
      associations between obesity and cardiac dimensions in a separate healthy but
      less restricted sample of 411 men and 503 women. CONCLUSIONS: Gender-specific M
      mode reference values and nomograms, with mean and 95th percentile values for
      echocardiographic dimensions as a function of height, are reported. The use of
      body surface area as means of body size adjustment is called into question.

PMID- 7560598
TI  - Intraoperative validation of mitral inflow determination by transesophageal
      echocardiography: comparison of single-plane, biplane and thermodilution
      techniques.
AB  - OBJECTIVES: This study investigated the accuracy of mitral inflow quantification
      using biplane transesophageal echocardiography. BACKGROUND: Mitral stroke volume
      can be reliably quantified by transthoracic Doppler echocardiography, but
      previous studies involving monoplane transesophageal echocardiography have
      yielded mixed results. METHODS: Thirty patients without mitral regurgitation were
      prospectively examined immediately before cardiovascular surgery. Mitral annulus
      diameter was measured in the transverse (d1) and longitudinal views (d2) by
      biplane transesophageal echocardiography. Assuming an elliptic shape, the annular
      area was calculated as pi d1d2/4; area was also calculated from single-plane data
      assuming a circular annular shape as pi d2/4. The time-velocity integral of
      mitral annular Doppler velocity was then multiplied by annular area to yield
      stroke volume. These data were compared with simultaneous thermodilution
      measurements by linear regression. RESULTS: Good correlations were observed
      between thermodilution (x) and Doppler (y) measurements of stroke volume (SV) (r
      = 0.86, p < 0.01, delta SV [y-x] = 2.64 +/- 9.86 ml for single four-chamber view;
      r = 0.77, p < 0.01, delta SV = 1.82 +/- 12.59 ml for two-chamber view; r = 0.94,
      p < 0.001, delta SV = 1.78 +/- 5.90 ml for biplane measurements) with similar
      data for cardiac output (r = 0.82, r = 0.74 and r = 0.92, respectively). The
      biplane measurements were most accurate and had less variability in individual
      patients (p < 0.05). This finding was supported by a numerical model that
      demonstrated (for an ellipse of eccentricity 1.5:1) that even maximal
      misalignment of biplane diameters yielded only 8% area overestimation, whereas
      single-plane calculations assuming a circular shape produced a variation in area
      of 225%. CONCLUSIONS: This study validates the accuracy of measurements of mitral
      inflow using biplane transesophageal echocardiography with potential application
      for quantification of valvular regurgitation in the operating room. The results
      are further generalizable, indicating that orthogonal biplane measurements are
      both necessary and sufficient to ensure accuracy in area calculation for any
      elliptic structure.

PMID- 7560599
TI  - Oral L-arginine inhibits platelet aggregation but does not enhance endothelium
      dependent dilation in healthy young men.
AB  - OBJECTIVES: Our aim was to assess the effect of oral L-arginine on endothelial or
      platelet physiology in humans. BACKGROUND: L-Arginine is the substrate for nitric
      oxide synthesis, and in cholesterol-fed rabbits, oral L-arginine improves
      endothelium-dependent dilation, inhibits platelet aggregation and reduces
      atheroma. In hypercholesterolemic humans, intravenous L-arginine immediately
      improves endothelium-dependent dilation; however, the vascular effects of oral L
      arginine in healthy humans have not previously been investigated. METHODS: In a
      prospective, double-blind, randomized crossover trial, 12 healthy young men 27 to
      37 years old took L-arginine (7 g three times daily) or placebo for 3 days each,
      separated by a washout period of 7 to 14 days. RESULTS: After L-arginine, plasma
      levels of arginine (mean +/- SEM 303 +/- 36 vs. 128 +/- 12 mumol/liter, p = 0.01)
      and urea (6.7 +/- 0.5 vs. 5.2 +/- 0.2 mmol/liter, p < 0.01) were higher than
      levels measured after placebo, and platelet aggregation in response to adenosine
      diphosphate was markedly impaired (37 +/- 12% vs. 81 +/- 3%, p = 0.02). The
      inhibition of platelet aggregation correlated with the plasma level of L-arginine
      (r = 0.74, p = 0.01), and it could be completely or partially reversed by ex vivo
      incubation with N-monomethyl-L-arginine, a specific nitric oxide synthase
      inhibitor. Platelet cyclic guanosine monophosphate levels were higher after oral
      L-arginine than at baseline (1.91 +/- 0.46 vs. 1.38 +/- 0.40 pmol/10(9)
      platelets, p = 0.04). No changes were seen in fasting lipid levels, heart rate,
      blood pressure, endothelium-dependent dilation of the brachial artery (measured
      in response to reactive hyperemia, using external vascular ultrasound) (6.1 +/-
      0.7% vs. 6.5 +/- 0.7%, p = NS) or in plasma levels of nitrosylated proteins (a
      marker of in vivo nitric oxide production) (3.5 +/- 0.5 vs. 3.3 +/- 0.4
      mumol/liter, p = NS) 1 to 1.5 h after the last dose of L-arginine. CONCLUSIONS:
      In these healthy young adult men, oral L-arginine inhibited platelet aggregation
      by way of the nitric oxide pathway. However, it had no effect on systemic
      hemodynamic variables, plasma nitrosylated protein levels or endothelium
      dependent dilation. Therefore, at certain doses, oral L-arginine may result in a
      relatively platelet-specific increase in nitric oxide production.

PMID- 7560600
TI  - Family history of severe cardiovascular disease in Marfan syndrome is associated
      with increased aortic diameter and decreased survival.
AB  - OBJECTIVES: We attempted to determine whether a family history of severe
      cardiovascular disease in patients with the Marfan syndrome is associated with
      increased aortic dilation or decreased survival, or both. BACKGROUND: The
      prognostic importance of a family history of severe cardiovascular disease in
      patients with the Marfan syndrome has been incompletely examined. We hypothesized
      that such a family history would correlate with increased aortic dilation and
      would be associated with decreased survival. METHODS: One hundred eight affected
      patients and 48 unaffected family members from 33 multigenerational families with
      the Marfan syndrome underwent echocardiographic measurement of the aortic root,
      arch and mid-abdominal aorta. Date of birth and age at death ascertained from
      family pedigrees were used to perform life table analysis and estimate survival.
      RESULTS: Aortic root and arch diameters were significantly greater in patients
      with a family history of severe cardiovascular disease than in patients without
      such a family history. Of subjects in the highest quartile for aortic size, > 80%
      had such a family history in contrast to < 10% of those in the lowest quartile
      (chi-square 57.37, p < 0.00001). Mean age at death and cumulative probability of
      survival were significantly lower in patients with such a family history.
      CONCLUSIONS: Among patients with the Marfan syndrome, aortic dilation is greater
      and life expectancy shorter in those with a family history of severe
      cardiovascular manifestations. These data suggest that such a family history is
      an important risk factor for cardiovascular events in patients with the Marfan
      syndrome.

PMID- 7560601
TI  - Gender differences and aging: effects on the human heart.
AB  - OBJECTIVES: This study investigated the changes in myocyte size and number in the
      left and right ventricles that occur with aging in the female and male heart.
      BACKGROUND: Differences in life span between women and men may be related to a
      better preservation of myocardial structure in the female heart with aging. On
      this basis, the hypothesis was advanced that the aging process has a different
      impact on the integrity of the myocardium in the two genders. METHODS:
      Morphometric methodologies were applied to analyze the changes in number and size
      of ventricular myocytes in the hearts of 53 women and 53 men. The changes in
      mononucleated and binucleated myocytes with age were determined in enzymatically
      dissociated cells. The age interval examined varied from 17 to 95 years. RESULTS:
      Aging was associated with a preservation of ventricular myocardial mass,
      aggregate number of mononucleated and binucleated myocytes, average cell diameter
      and volume in the female heart. In contrast, nearly 1 g/year of myocardium was
      lost in the male heart, and this phenomenon accounted for the loss of
      approximately 64 million cells. This detrimental effect involved the left and
      right sides of the heart. In the remaining cells, myocyte cell volume increased
      at a rate of 158 microns3/year in the left and 167 microns3/year in the right
      ventricle. CONCLUSIONS: Aging does not lead to myocyte cell loss and myocyte
      cellular reactive hypertrophy in women, indicating that gender differences may
      play a significant role in the detrimental effects of the aging process on the
      heart.

PMID- 7560602
TI  - Cellular mechanisms of ventricular bipolar electrograms showing double and
      fractionated potentials.
AB  - OBJECTIVES: This study sought to determine the types of trans-membrane action
      potentials associated with bipolar electrograms that show double and fractionated
      potentials. BACKGROUND: The cellular correlates of ventricular bipolar
      electrograms showing double potentials and fractionated low amplitude potentials
      remain poorly defined. METHODS: A bipolar electrogram (1-cm interelectrode
      distance [6F, USCI]) and two transmembrane action potentials (within 1 mm of each
      pole) were recorded simultaneously in 12 isolated canine right ventricular
      endocardial preparations (2 x 1 cm, 2 mm thick). The long axis of the bipolar
      electrode was parallel to the long axis of the superficial endocardial fibers,
      and the recordings were made at 40 to 500 Hz. RESULTS: The following phenomena
      were associated with double potentials: 1) an increase in conduction time between
      the two poles of the bipole during a) the propagation of premature action
      potentials (7 of 12 tissues in 4 mmol/liter extracellular potassium ion
      concentration [K+]o); b) rapid pacing and premature stimuli (3 of 6 in 9
      mmol/liter [K+]o); and c) the propagation of slow responses induced by barium
      chloride (4 mmol/liter). There was a positive correlation between conduction time
      (CT) and interspike interval (IPI) of the double potential (IPI [ms] = 0.5 x CT
      [ms] + 35) during early afterdepolarizations induced by barium chloride (4
      mmol/liter) superfusion (three of six tissues). The following events were
      associated with fractionated electrograms: 1) propagation of induced graded
      responses (six tissues) in 4 mmol/liter [K+]o; 2) induced reentry at cycle
      lengths of 140 to 170 ms in 9 mmol/liter [K+]o (four of six tissues); and 3)
      asynchronous afterdepolarizations induced by 4 mmol/liter barium chloride (four
      of six tissues). CONCLUSIONS: Endocardial double potentials and fractionated
      electrograms seen on clinically used bipolar electrodes occur under conditions of
      slowed or discontinuous conduction and induced reentry and during asynchronous
      automatic firing initiated by afterdepolarizations. Caution must be exercised in
      interpreting such bipolar electrograms because more than one type of cellular
      action potential may cause these abnormal electrographic results.

PMID- 7560603
TI  - The commercialization of medicine: "business" ethics versus "medical" ethics.

PMID- 7560604
TI  - Education update: 1995. Training Programs in the United States in Adult
      Cardiology, Pediatric Cardiology and Cardiothoracic Surgery.

PMID- 7560605
TI  - Effect of angina pectoris on myocardial protection in patients with reperfused
      anterior wall myocardial infarction: retrospective clinical evidence of
      preconditioning?

PMID- 7560606
TI  - Radiofrequency catheter ablation for management of symptomatic ventricular
      ectopic activity.
AB  - OBJECTIVES: This study assessed the useful role of intracardiac mapping and
      radiofrequency catheter ablation in eliminating drug-refractory monomorphic
      ventricular ectopic beats in severely symptomatic patients. BACKGROUND:
      Ventricular ectopic activity is commonly encountered in clinical practice.
      Usually, it is not associated with life-threatening consequences in the absence
      of significant structural heart disease. However, frequent ventricular ectopic
      beats can be extremely symptomatic and even incapacitating in some patients.
      Currently, reassurance and pharmacologic therapy are the mainstays of treatment.
      There has been little information on the use of catheter ablation in such
      patients. METHODS: Ten patients with frequent and severely symptomatic
      monomorphic ventricular ectopic beats were selected from three tertiary care
      centers. The mean frequency +/- SD of ventricular ectopic activity was 1,065 +/-
      631 beats/h (range 280 to 2,094) as documented by baseline 24-h ambulatory
      electrocardiographic (ECG) monitoring. No other spontaneous arrhythmias were
      documented. These patients had previously been unable to tolerate or had been
      unsuccessfully treated with a mean of 5 +/- 3 antiarrhythmic drugs. The site of
      origin of ventricular ectopic activity was accurately mapped by using earliest
      endocardial activation time during ectopic activity or pace mapping, or both.
      RESULTS: During electrophysiologic study, no patient had inducible ventricular
      tachycardia. The ectopic focus was located in the right ventricular outflow tract
      in nine patients and in the left ventricular posteroseptal region in one patient.
      Frequent ventricular ectopic beats were successfully eliminated by catheter
      delivered radiofrequency energy in all 10 patients. The mean number of
      radiofrequency applications was 2.6 +/- 1.3 (range 1 to 5). No complications were
      encountered. During a mean follow-up period of 10 +/- 4 months, no patient had a
      recurrence of symptomatic ectopic activity, and 24-h ambulatory ECG monitoring
      showed that the frequency of ventricular ectopic activity was 0 beat/h in seven
      patients, 1 beat/h in two patients and 2 beats/h in one patient. CONCLUSIONS:
      Radiofrequency catheter ablation can be successfully used to eliminate
      monomorphic ventricular ectopic activity. It may therefore be a reasonable
      alternative for the treatment of severely symptomatic, drug-resistant monomorphic
      ventricular ectopic activity in patients without significant structural heart
      disease.

PMID- 7560607
TI  - Radiofrequency catheter ablation of benign ventricular ectopic beats: a therapy
      in search of a disease?

PMID- 7560608
TI  - Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial
      fibrillation: prospective comparison of sotalol versus quinidine.
AB  - OBJECTIVES: This study compared the efficacy and safety of sotalol and quinidine
      for conversion and prevention of recurrent atrial fibrillation. BACKGROUND:
      Atrial fibrillation is the most common arrhythmia. Pharmacologic therapy has been
      advocated for both immediate restoration of sinus rhythm and prevention of
      recurrent atrial fibrillation. Quinidine is the therapeutic mainstay for both
      purposes, but its safety has recently been questioned. Although sotalol has been
      used successfully to maintain sinus rhythm after direct current cardioversion,
      its efficacy in pharmacologically reverting atrial fibrillation has not been
      examined. METHODS: Fifty consecutive patients with persistent atrial fibrillation
      were randomized to receive quinidine or sotalol for up to 7 days to restore sinus
      rhythm. Patients were followed up for 6 months. RESULTS: Quinidine was more
      effective than sotalol in terminating atrial fibrillation (60% vs. 20%, p =
      0.009). When nonresponders to drug therapy underwent subsequent direct current
      cardioversion, total conversion rates in the quinidine and sotalol groups were
      comparable (88% vs. 68%, p = 0.17), as was the efficacy of the two drugs in
      preventing recurrent atrial fibrillation. Side effects necessitating drug
      discontinuation were more often observed with quinidine. No patient receiving
      sotalol but four patients receiving quinidine had drug-associated arrhythmia
      (torsade de pointes in three patients, sustained ventricular tachycardia in one
      patient). Precordial QT dispersion determined on the surface electrocardiogram
      (ECG) increased with quinidine (mean +/- SD 34 +/- 9 vs. 44 +/- 16 ms, p = 0.02),
      indicating enhanced inhomogeneity in ventricular repolarization. There was no
      change in QT dispersion in patients receiving sotalol (36 +/- 18 vs. 40 +/- 17
      ms, p = 0.44). CONCLUSIONS: Quinidine is more effective than sotalol in
      terminating atrial fibrillation but is associated with more side effects. The
      proarrhythmic risk may be related to quinidine's propensity to increase disparity
      in ventricular repolarization. This risk warrants careful ECG monitoring during
      the 1st 4 to 7 days of therapy. Because most proarrhythmic effects occurred
      shortly after restoration of sinus rhythm, observation should continue > or = 2
      to 3 days after sinus rhythm is reestablished.

PMID- 7560609
TI  - Association between QT dispersion and autonomic dysfunction in patients with
      diabetes mellitus.
AB  - OBJECTIVES: We hypothesized that QT dispersion would be increased in patients
      with diabetes mellitus and autonomic dysfunction and that QT dispersion would be
      related to abnormal iodine-123 (I-123) metaiodobenzylguanidine (MIBG) uptake.
      BACKGROUND: Patients with diabetes mellitus and autonomic dysfunction have an
      increased incidence of sudden death. This event may be due to a sympathetic
      imbalance causing disturbances of repolarization. QT dispersion has recently been
      demonstrated to reflect dispersion of ventricular refractoriness and is a marker
      of arrhythmogenic potential. Uptake of I-123 MIBG is a reliable measure of
      whether the tissue examined receives sympathetic neuronal innervation. METHODS:
      Fifty-one diabetic patients and 11 normal subjects were studied. All patients had
      clinical evaluation for autonomic dysfunction (defined as at least two abnormal
      heart rate and blood pressure responses to five validated tests). Rest 12-lead
      electrocardiograms were recorded for measurement of QT dispersion, defined as the
      longest QT interval minus the shortest QT interval, and corrected for heart rate
      using Bazett's formula. Visual and quantitative measurements of I-123 MIBG uptake
      were performed using I-123 MIBG, and technetium-99m sestamibi uptake was used to
      assess perfusion. RESULTS: Thirty-five diabetic patients had autonomic
      dysfunction. Corrected QT dispersion was significantly greater in the patients
      than in the normal subjects (p = 0.02). The I-123 MIBG scores were also
      significantly greater in patients with than without autonomic dysfunction (p =
      0.0004) and in normal subjects (p = 0.008). There was no correlation between QT
      dispersion and I-123 MIBG uptake score (r = 0.006, p = 0.97). CONCLUSIONS:
      Diabetic patients with autonomic dysfunction have increased QT dispersion and
      larger I-123 MIBG uptake defects. This finding suggests that such patients have a
      greater inhomogeneity of repolarization. The lack of correlation between QT
      dispersion and I-123 MIBG uptake suggests that these abnormalities are mediated
      by different mechanisms.

PMID- 7560610
TI  - High prevalence of antibodies against beta 1- and beta 2-adrenoceptors in
      patients with primary electrical cardiac abnormalities.
AB  - OBJECTIVES: This study sought to determine the prevalence of autoantibodies
      directed against the beta-adrenoceptors in patients with primary electrical
      cardiac abnormalities, including atrial arrhythmias, ventricular arrhythmias and
      conduction disturbances, in the absence of any other cardiac abnormality.
      BACKGROUND: Using synthetic peptides corresponding to the predicted sequences for
      the second extracellular loop of the human beta 1- and beta 2-adrenoceptors as
      antigenic targets, autoantibodies directed against the beta-adrenoceptors were
      recently shown to occur in patients with idiopathic dilated cardiomyopathy and
      Chagas' heart disease. METHODS: Eighty-six patients (57 with primary electrical
      abnormalities, 29 with idiopathic dilated cardiomyopathy) and 101 healthy and
      cardiopathic control subjects were studied. Antibodies against the beta 1- and
      beta 2-peptides were detected with an enzyme immunoassay performed in blinded
      manner. In nine selected (seropositive) cases, the immunoglobulin G (IgG)
      fraction was tested for functional effects on the rate of beating of cultured
      neonatal rat cardiomyocytes. RESULTS: Antibodies recognizing the beta 1- and beta
      2-peptides were found in 11 (52.3%) of 21 patients with ventricular arrhythmias
      (p < 0.01), 5 (35.7%) of 14 patients with conduction disturbances (p < 0.05), 3
      (13.6%) of 22 patients with atrial arrhythmias (p > 0.05) and 11 (37.9%) of 29
      patients with dilated cardiomyopathy (p < 0.05) compared with 15 (14.8%) of 101
      control subjects. A rapid increase in the rate of beating of the cultured
      cardiomyocytes was induced by IgG from a selected group of patients, suggesting
      an agonist-like interaction with a functional epitope. This response was mediated
      by stimulation of both the beta 1- and beta 2-adrenoceptors in the patients with
      primary ventricular arrhythmias but only the beta 1-adrenoceptors in the patients
      with idiopathic dilated cardiomyopathy. CONCLUSIONS: Primary ventricular
      arrhythmias and conduction disturbances, like idiopathic cardiomyopathy, show a
      high prevalence of antibodies interacting with functional epitopes of the beta
      adrenoceptors, suggesting a common or similar abnormal immunoregulatory process.

PMID- 7560611
TI  - Evaluation of myocardial ischemia using a rest metabolism/stress perfusion
      protocol with fluorine-18 deoxyglucose/technetium-99m MIBI and dual-isotope
      simultaneous-acquisition single-photon emission computed tomography.
AB  - OBJECTIVES: This study sought to develop a dual-isotope single-acquisition single
      photon emission computed tomographic (SPECT) protocol using a multihead SPECT
      camera equipped with an ultra-high energy collimator to evaluate rest
      metabolism/stress perfusion simultaneously with fluorine-18 (F-18)
      deoxyglucose/technetium-99m (Tc-99m) 2-hexakis-2-methoxy-2-methylpropyl
      isonitrile (MIBI). BACKGROUND: The most accurate and logistic method of
      identifying injured but viable myocardium remains a diagnostic challenge.
      METHODS: Sixty-five patients were given 25 to 50 g of glucose and, after
      approximately 60 min, an injection of 370 MBq (10 mCi) of F-18
      fluorodeoxyglucose. After a 35-min distribution phase, patients underwent
      exercise or pharmacologic stress followed by administration of 925 MBq (25 mCi)
      of Tc-99m MIBI. Five patients underwent F-18 fluorodeoxyglucose position emission
      tomography before dual-isotope SPECT: RESULTS: With a window of 20% for both
      photopeaks and a technetium-99m/fluorine-18 concentration of 3.2:1, the
      "spillover" from fluorine-18 into the technetium-99m window is < 6% of the total
      counts in the window in patients with a normal distribution of both
      radiopharmaceuticals. Phantom images clearly demonstrated cardiac defects
      measuring 2 x 1 and 2 x 0.5 cm. There was no significant difference in the images
      of the five patients who underwent both positron emission tomography and SPECT:
      Fifty-seven patients (mean [+/- SD] age 55 +/- 15 years, range 25 to 83; 38 men,
      19 women) had satisfactory images and were included in the study. Twenty-one
      patients had normal study results; 15 had mismatched defects; 14 had matched
      defects; and 7 had both matched and mismatched defects. Twenty-three patients
      (mean age 54 +/- 6 years, range 30 to 83; 14 men, 9 women) underwent coronary
      angiography within 3 months of dual-isotope SPECT: There were seven normal
      studies, eight with mismatched defects, one with a matched defect and seven with
      matched and mismatched defects. When stenosis > 70% was used as the criterion for
      a diagnosis of coronary artery disease, dual-isotope SPECT had a sensitivity of
      100%, specificity of 88%, positive predictive value of 93%, negative predictive
      value of 100% and an accuracy of 96%. CONCLUSIONS: Dual-isotope SPECT may provide
      an alternative, accurate, cost-effective method to nitrogen-13 ammonia/F-18
      fluorodeoxyglucose positron emission tomography or thallium-201 reinjection for
      identifying injured or dysfunctional but viable myocardium.

PMID- 7560612
TI  - Long-term prediction of major ischemic events by exercise thallium-201 single
      photon emission computed tomography. Incremental prognostic value compared with
      clinical, exercise testing, catheterization and radionuclide angiographic data.
AB  - OBJECTIVES: This study sought to evaluate the prognostic role of exercise
      thallium-201 (Tl-201) single-photon emission computed tomography (SPECT) in
      patients with known or suspected coronary artery disease. BACKGROUND: Compared
      with planar Tl-201 scintigraphy, Tl-201 SPECT allows enhanced assessment of
      myocardial perfusion abnormalities. However, the long-term prognostic value of
      exercise Tl-201 SPECT has not been ascertained and compared with that of other
      techniques of investigation. METHODS: Predictors of ischemic events were sought
      in 217 patients with known or suspected coronary artery disease who underwent
      exercise Tl-201 SPECT, coronary angiography and rest radionuclide angiography and
      who initially received medical therapy. Predictive values were determined using
      Cox proportional hazards regression models. RESULTS: During a mean (+/- SD)
      follow-up period of 70 +/- 19 months, 29 patients had a major ischemic event
      (cardiac death or myocardial infarction). Total extent of exercise defects was
      the best independent predictor by Tl-201 SPECT of major events (p < 0.001) and
      provided additional prognostic information compared with clinical, exercise
      testing and catheterization variables (p < 0.02). Extent of reversible Tl-201
      SPECT perfusion defects provided additional prognostic information compared with
      extent of irreversible defects (p < 0.001) and was the sole Tl-201 SPECT variable
      providing additional prognostic information compared with radionuclide left
      ventricular ejection fraction (p < 0.02). CONCLUSIONS: Total extent of exercise
      Tl-201 SPECT defects is a powerful long-term predictor of major ischemic events
      that enhances the prediction provided by clinical, exercise testing and coronary
      angiographic data. In view of its prognostic significance, extent of reversible
      Tl-201 SPECT defects might provide original information about improving prognosis
      by coronary revascularization.

PMID- 7560613
TI  - Prognostic value of high dose dipyridamole echocardiography in patients with
      chronic coronary artery disease and preserved left ventricular function.
AB  - OBJECTIVES: The prognostic value of dipyridamole echocardiography was assessed in
      patients with chronic coronary artery disease and preserved left ventricular
      function. BACKGROUND: Few data are available on the prognostic value of
      dipyridamole echocardiography in patients with a low risk of cardiac events.
      METHODS: Two hundred sixty-eight consecutive patients with stable, proven or
      suspected coronary artery disease and ejection fraction > or = 0.40 underwent
      high dose (up to 0.84 mg/kg body weight) dipyridamole echocardiography. In 204
      patients definite exercise electrocardiographic (ECG) results were also
      available. RESULTS: During a mean (+/- SD) follow-up period of 16 +/- 8 months
      (range 6 to 36), 33 spontaneous events occurred: 15 "hard" events (cardiac death
      [n = 6], myocardial infarction [n = 9]) and 18 "soft" events (unstable angina).
      Events occurred more frequently in patients with positive findings on
      dipyridamole echocardiography (59% vs. 3%, p < 0.001; hard events 24% vs. 2%, p <
      0.01). A positive response at the low dose (up to 0.56 mg/kg) identified patients
      with a high incidence of hard events (7 of 16 patients, sensitivity 50%,
      specificity 96%). In patients with an exercise ECG, a comparable sensitivity for
      cardiac events was found (89% vs. 93%, p = NS), but dipyridamole echocardiography
      was more specific (91% vs. 61%, p < 0.01). A positive response on the low work
      load exercise ECG (< 8 min) and a positive response to low dose dipyridamole
      echocardiography had similar accuracy (82% vs. 90%, p = NS). Cox analysis
      identified dipyridamole echocardiography as the best predictor of cardiac events
      (odds ratio [OR] 20.9, 95% confidence interval [CI] 10.8 to 37.9); the highest
      risk of hard events was found in patients with a positive response to low dose
      dipyridamole echocardiography (OR 25.4, 95% CI 12.2 to 54.1). CONCLUSIONS: In
      patients with chronic coronary artery disease and a low incidence of cardiac
      events, dipyridamole echocardiography was effective in prognostic stratification,
      and positive low work load exercise ECG results were a reliable predictor of
      subsequent events. Consequently, dipyridamole echocardiography should be
      considered a complementary tool in the presence of high work load positivity or
      ambiguous exercise ECG results.

PMID- 7560614
TI  - Recurrence of angina after coronary artery bypass surgery: predictors and
      prognosis (CASS Registry). Coronary Artery Surgery Study.
AB  - OBJECTIVES: This study sought to define the predictors and prognosis of
      postoperative angina in patients undergoing coronary artery bypass surgery.
      BACKGROUND: Angina recurs in the first postoperative year in 20% to 30% of
      patients after coronary artery bypass surgery. The Coronary Artery Surgery Study
      Registry provides an opportunity to study the predictors and prognosis of
      postoperative angina in a large sample. METHODS: All patients with isolated
      coronary artery bypass surgery in the registry were identified, and anginal
      status was determined on a yearly basis. The influence of angina on mortality,
      recurrent myocardial infarction and need for reoperation was determined. RESULTS:
      Angina recurred in the first year in 24% of patients and by the sixth year in
      40%. The significant predictors in a multivariate analysis were minimal coronary
      artery disease, preoperative angina, use of vein grafts only, previous myocardial
      infarction, incomplete revascularization, female gender, smoking and younger age.
      In subsequent years important predictors were angina in the first postoperative
      year, female gender, younger age and incomplete revascularization. The presence
      of angina in the first postoperative year was associated with more frequent
      myocardial infarction (p = 0.04) and greater need for reoperation (p = 0.003) but
      did not affect survival during the 6-year follow-up period. CONCLUSIONS: These
      findings show that the predictors of postoperative angina are features that are
      or could be predicted before bypass surgery. Thus, patients with these features
      before bypass surgery could be advised that they would be more likely to
      experience postoperative angina than those without these features. Postoperative
      angina is associated with an increased risk of late myocardial infarction and
      reoperation.

PMID- 7560615
TI  - Prognostic significance of nonfatal reinfarction during 3-year follow-up: results
      of the Thrombolysis in Myocardial Infarction (TIMI) phase II clinical trial. The
      TIMI Investigators.
AB  - OBJECTIVES: This study sought to assess the independent contribution of nonfatal
      reinfarction to the risk of subsequent death in patients with acute myocardial
      infarction undergoing thrombolytic therapy. BACKGROUND: A composite of
      "unsatisfactory outcomes" as an end point has increased statistical power and
      facilitated evaluation of evolving treatment regimens in acute myocardial
      infarction. The significance of nonfatal reinfarction as a component of a
      composite end point has not been evaluated in the thrombolytic era. METHODS:
      Event rate of nonfatal reinfarction over 3-year follow-up was evaluated in
      patients with acute myocardial infarction entered into the Thrombolysis in
      Myocardial Infarction Phase II trial. The independent risk of nonfatal
      reinfarction for subsequent death within various time intervals of follow-up was
      determined. The mortality rate after nonfatal reinfarction was compared with that
      of a matched control group. RESULTS: During 3-year follow-up, 349 of 3,339
      patients had a nonfatal reinfarction. Univariate predictors were history
      (antedating the index event) of angina (p = 0.01), hypertension (p = 0.01),
      multivessel disease (p = 0.007) and not a current smoker (p = 0.003); the latter
      was an independent predictor (relative risk [RR] 1.3, 99% confidence interval
      [CI] 1.0 to 1.8). Forty-three of the 349 patients with a nonfatal reinfarction
      died: RR for death (vs. patients without a nonfatal reinfarction) was 1.9 (99% CI
      1.1 to 3.2) if reinfarction occurred within 42 days of study entry, 6.2 (99% CI
      3.0 to 12.9) if reinfarction occurred between 43 and 365 days and 2.9 (99% CI 0.6
      to 13.4) if reinfarction occurred between 366 days and 3 years. The cumulative 3
      year death rate was 14.1% in patients with a nonfatal reinfarction compared with
      7.9% (p < 0.01) in a matched control group. Univariate predictors of death after
      nonfatal reinfarction were age > or = 65 years (p < 0.001), not low risk category
      (p = 0.015) and history of heart failure before the index event (p < 0.001). Age
      > or = 65 years was the only independent predictor (RR 5.4, 99% CI 2.3 to 12.4).
      CONCLUSIONS: Nonfatal reinfarction is a strong and independent predictor for
      subsequent death. It represents a powerful component for a composite end point in
      patients who received thrombolytic therapy after acute myocardial infarction.

PMID- 7560616
TI  - Stress echocardiographic results predict risk of reinfarction early after
      uncomplicated acute myocardial infarction: large-scale multicenter study. Echo
      Persantine International Cooperative (EPIC) Study Group.
AB  - OBJECTIVES: This study sought to assess the value of dipyridamole
      echocardiography in predicting reinfarction in patients evaluated early after
      uncomplicated acute myocardial infarction. BACKGROUND: The identification of
      future nonfatal reinfarction seems an elusive target for physiologic testing.
      However, a large sample population is needed to detect minor differences in
      phenomena with a low event rate. METHODS: We assessed the value of dipyridamole
      echocardiography in predicting reinfarction in 1,080 patients (mean [+/- SD] age
      56 +/- 9 years; 926 men, 154 women) evaluated early (10 +/- 5 days) after
      uncomplicated acute myocardial infarction and followed up for 14 +/- 10 months.
      RESULTS: Submaximal studies due to limiting side effects occurred in 14 patients
      (1.3%); these test results were included in the analysis. Results of dipyridamole
      echocardiography were positive in 475 patients (44%). During follow-up, there
      were 50 reinfarctions: 45 nonfatal, 5 fatal (followed by cardiac death < or = 4
      days after reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30
      patients with positive and 20 with negative results (6.3% vs. 3.3%, p < 0.01).
      Nonfatal reinfarction occurred in 25 patients with positive and 20 with negative
      results (5% vs. 3.3%, p < 0.05). Reinfarction was fatal in 5 of 30 patients with
      positive and in none of 20 with negative results (16.6% vs. 0%, p = 0.07). The
      relative risk of reinfarction was 1.9. CONCLUSIONS: Dipyridamole
      echocardiographic positivity identifies patients evaluated early after
      uncomplicated acute myocardial infarction at higher risk of reinfarction,
      especially fatal reinfarction.

PMID- 7560617
TI  - Cost-effectiveness of captopril therapy after myocardial infarction.
AB  - OBJECTIVES: This study sought to assess the cost-effectiveness of captopril
      therapy for survivors of myocardial infarction. BACKGROUND: The recent
      randomized, controlled Survival and Ventricular Enlargement (SAVE) trial showed
      that captopril therapy improves survival in survivors of myocardial infarction
      with an ejection fraction < or = 40%. The present ancillary study was designed to
      determine how the costs required to achieve this increase in survival compared
      with those of other medical interventions. METHODS: We developed a decision
      analytic model to assess the cost-effectiveness of captopril therapy in 50- to 80
      year old survivors of myocardial infarction with an ejection fraction < or = 40%.
      Data on costs, utilities (health-related quality of life weights) and 4-year
      survival were obtained directly from the SAVE trial, and long-term survival was
      estimated using a Markov model. In one set of analyses, we assumed that the
      survival benefit associated with captopril therapy would persist beyond 4 years
      (persistent-benefit analyses), whereas in another set we assumed that captopril
      therapy incurred costs but no survival benefit beyond 4 years (limited-benefit
      analyses). RESULTS: In the limited-benefit analyses, the incremental cost
      effectiveness of captopril therapy ranged from $3,600/quality-adjusted life-year
      for 80-year old patients to $60,800/quality-adjusted life-year for 50-year old
      patients. In the persistent-benefit analyses, incremental cost-effectiveness
      ratios ranged from $3,700 to $10,400/quality-adjusted life-year, depending on
      age. The outcome was generally not sensitive to changes in estimates of variables
      when they were varied individually over wide ranges. In a "worst-case" analysis,
      incremental cost-effectiveness ratios for captopril therapy remained favorable
      ($8,700 to $29,200/quality-adjusted life-year) for 60- to 80-year old patients
      but were higher ($217,600/quality-adjusted life-year) for 50-year old patients.
      CONCLUSIONS: We conclude that the cost-effectiveness of captopril therapy for 50-
      to 80-year old survivors of myocardial infarction with a low ejection fraction
      compares favorably with other interventions for survivors of myocardial
      infarction.

PMID- 7560618
TI  - Cost-effectiveness analysis and clinical practice.

PMID- 7560619
TI  - Peripheral vascular complications in the Coronary Angioplasty Versus Excisional
      Atherectomy Trial (CAVEAT-I).
AB  - OBJECTIVES: In-hospital peripheral vascular complications of balloon angioplasty
      were compared with those of directional atherectomy in the Coronary Angioplasty
      Versus Excisional Atherectomy Trial (CAVEAT-I) to identify patients at risk and
      evaluate costs and outcomes. BACKGROUND: The incidence, costs and outcomes of
      peripheral vascular complications after coronary intervention have not been fully
      characterized as a function of randomly assigned therapy. METHODS: At 35 sites in
      the United States and Europe, 1,012 patients were randomized. Peripheral vascular
      complications were defined as the composite of pulse loss, pseudoaneurysm,
      hematoma > 4 cm in diameter or groin hemorrhage necessitating blood transfusion.
      Logistic models were derived to 1) predict these complications from baseline and
      procedural characteristics, 2) test the relevance of randomization assignment,
      and 3) assess their impact on hospital costs and long-term outcomes. RESULTS:
      Sixty-seven patients (6.6%) developed peripheral vascular complications, of whom
      15 (22.4%) required a blood transfusion, 14 (20.9%) underwent vascular surgery,
      and 2 (3.0%) died. Both in-hospital deaths occurred in patients with peripheral
      vascular complications. There was no difference in composite peripheral vascular
      complication rates among patients randomized to angioplasty or atherectomy.
      Greater age, female gender, postprocedural heparin and intraaortic balloon
      counterpulsation were predictive of increased risk. In a representative 60%
      subset, mean hospital costs increased from $9,583 in patients without to $18,350
      in those with peripheral vascular complications (p = 0.0001). The unadjusted
      mortality rate at 1 year was 7.5% for patients with peripheral vascular
      complications compared with 1.1% for all others (p = 0.0001). These complications
      identified patients at greater risk of death, myocardial infarction or repeat
      revascularization at 30 days and 1 year. The atherectomy group had a trend toward
      more frequent deaths and myocardial infarction. CONCLUSIONS: Directional
      atherectomy and balloon angioplasty had similar in-hospital peripheral vascular
      complication rates. Female gender, greater age, postprocedural heparin and
      intraaortic balloon counterpulsation were predictive of higher risk. The twofold
      increase in cost and sevenfold increase in long-term deaths highlight the need to
      prevent these periprocedural events and monitor patients closely.

PMID- 7560620
TI  - Development and validation of simplified predictive index for major complications
      in contemporary percutaneous transluminal coronary angioplasty practice. The
      Registry Committee of the Society for Cardiac Angiography and Interventions.
AB  - OBJECTIVES: This study was designed to determine the preprocedural risk factors
      for major complications (emergent coronary bypass surgery, myocardial infarction
      or death) of coronary angioplasty and to derive and validate a simplified index
      that predicts patients' a priori risk of complications. BACKGROUND: Previous
      studies of risk factors for complications after coronary angioplasty may not be
      generalizable to current, broad-based angioplasty practice. Furthermore, to our
      knowledge a clinically useful predictive index has not been derived and
      independently validated. METHODS: From data collected prospectively for the
      Registry of the Society for Cardiac Angiography and Interventions for 1992,
      multivariable logistic regression was used to determine which variables were
      independently associated with complications in 10,622 first angioplasty
      procedures. Stepwise regression and receiver operating characteristic curves then
      were used in this registry to develop a predictive index for complications that
      was validated using 5,250 first angioplasty procedures in the 1993 registry.
      RESULTS: Predictors of major complications were multivessel disease, unstable
      angina, recent myocardial infarction, type C lesion or left main angioplasty,
      shock, age, geographic region and absence of previous coronary bypass surgery.
      The derived predictive index consisted of the first six of these variables plus
      aortic valve disease and classified patients into four risk groups: low (1.3%
      complications), moderate (2.8%), high (12.7%) and very high (29.7%) risk. This
      index demonstrated consistent reliability and discriminatory ability when applied
      to the 1993 data. CONCLUSIONS: Predictors of major complications identified in
      selected populations also apply currently in broad-based practice. From these
      variables, a predictive index can stratify patients into risk groups before
      angioplasty, thus aiding in risk assessment, resource allocation and risk
      adjustment.

PMID- 7560621
TI  - Immediate and late outcome of excimer laser and balloon coronary angioplasty: a
      quantitative angiographic comparison based on matched lesions.
AB  - OBJECTIVES: This study sought to compare acute lumen changes and late lumen
      narrowing during and after excimer laser-assisted balloon angioplasty, measured
      by quantitative coronary angiography, with the immediate and long-term outcome of
      balloon angioplasty alone. BACKGROUND: Although excimer laser coronary
      angioplasty is used as an adjunct or alternative to balloon angioplasty, limited
      comparative data exist regarding the immediate and long-term efficacy of excimer
      laser-assisted balloon angioplasty versus balloon angioplasty alone. METHODS: A
      series of 53 lesions in 47 consecutive patients successfully treated with excimer
      laser-assisted balloon angioplasty were individually matched after completion of
      6-month follow-up angiography with 53 successfully treated balloon angioplasty
      lesions according to vessel location, preprocedural minimal lumen diameter and
      reference diameter. Immediate and long-term angiographic results were assessed by
      an automated lumen contour detection algorithm. RESULTS: Before intervention in
      the laser and balloon angioplasty groups, respectively, minimal lumen diameter
      (mean +/- SD) was 0.73 +/- 0.47 and 0.74 +/- 0.46 mm, and reference diameter was
      2.71 +/- 0.42 and 2.72 +/- 0.41 mm. Laser angioplasty was followed by adjunctive
      balloon dilation in 50 lesions. Mean balloon diameter at maximal inflation was
      similar in both treatment groups (2.61 +/- 0.32 and 2.65 +/- 0.38 mm,
      respectively), resulting in similar minimal lumen diameters after intervention of
      1.77 +/- 0.41 and 1.78 +/- 0.34 mm, respectively. At follow-up angiography,
      minimal lumen diameter after excimer laser-assisted balloon angioplasty was 1.17
      +/- 0.63 mm, and that after balloon angioplasty alone was 1.46 +/- 0.67 mm (p =
      0.02). The angiographic restenosis rates at follow-up using the 50% diameter
      stenosis cutoff criterion were 57% and 34%, respectively (p = 0.02). CONCLUSIONS:
      Quantitative angiographic analysis of a matched group of 106 successfully treated
      coronary lesions showed a similar immediate outcome but reduced long-term
      efficacy of excimer laser-assisted balloon angioplasty compared with that after
      balloon angioplasty alone.

PMID- 7560623
TI  - Percutaneous revascularization of ostial saphenous vein graft stenoses.
AB  - OBJECTIVES: This study sought to evaluate the short-term results and long-term
      outcome of percutaneous revascularization of ostial saphenous vein graft stenoses
      in a large patient series. BACKGROUND: Previous studies have demonstrated that
      the results of balloon angioplasty for native coronary ostial stenoses are
      significantly worse than those for nonostial lesions. However, it is
      controversial whether interventions in patients with ostial saphenous vein grafts
      carry a similar prognosis. METHODS: We identified 68 consecutive patients with
      ostial (group I) and 72 consecutive patients with proximal, nonostial (group II)
      saphenous vein graft stenoses who underwent percutaneous angioplasty or
      directional atherectomy for a single new stenosis at the Cleveland Clinic between
      1986 and 1992. RESULTS: Success was achieved in 61 patients (89.7%) in group I
      and 64 (88.9%) in group II (p = 0.88). There were no differences in major
      procedural complications (death, Q wave infarction and bypass surgery) between
      the two groups. At a mean (+/- SD) follow-up of 23 +/- 17 months, 36 patients
      (64%) in group I had one or more adverse events (death, infarction, repeat
      coronary revascularization or cardiac-related hospital admission) compared with
      34 patients (58%) in group II (p = 0.87). Twenty-eight patients (50%) were angina
      free in group I compared with 33 (56%) in group II (p = 0.65). During the follow
      up period in group I, 7 patients died (13%), 10 had a myocardial infarction
      (18%), 11 had repeat bypass surgery (20%), 8 had repeat percutaneous
      interventions (14%), and 30 had one or more cardiac-related hospital admissions
      (54%). The incidence of these events was similar in group II except for a
      slightly higher incidence of myocardial infarction: 6 patients died (10%), 3 had
      a myocardial infarction (5%), 12 had repeat bypass surgery (20%), 12 had repeat
      percutaneous interventions (20%), and 26 had one or more cardiac-related hospital
      admissions (44%). CONCLUSIONS: Unlike ostial native coronary disease, the
      clinical, procedural and follow-up profile of ostial saphenous vein graft
      revascularization is not significantly worse than proximal nonostial disease.
      This finding may be related to the overall suboptimal results of percutaneous
      revascularization in saphenous vein grafts compared with native coronary arteries
      or to the unfavorable intrinsic properties of ostial native coronary arteries
      compared with ostial vein grafts.

PMID- 7560622
TI  - The Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) trial.
      Results of a multicenter randomized trial investigating the effects of high dose
      unfractionated heparin on angiographic restenosis and clinical outcome.
AB  - OBJECTIVES: We sought to determine whether 12,500 IU of unfractionated heparin
      given subcutaneously twice daily for 4 months after percutaneous transluminal
      coronary angioplasty beneficially influences the subsequent rate of angiographic
      restenosis and the incidence of clinical events. BACKGROUND: Heparin has been
      shown to exhibit powerful antiproliferative effects against smooth muscle cells
      in several animal models. METHODS: A randomized trial with blinded data analysis
      was undertaken to assess the effect of unfractionated subcutaneous heparin on
      angiographic restenosis after coronary angioplasty. After successful angioplasty,
      patients were randomized to receive no heparin or 12,500 IU of heparin given
      subcutaneously twice daily for 4 months. Quantitative coronary angiography was
      performed before angioplasty, immediately after angioplasty and at follow-up
      ("early" [before 4 months] or electively [at 4 months]). RESULTS: The study group
      comprised 339 patients, 167 randomly assigned to receive heparin, 172 to receive
      no heparin. Repeat cardiac catheterization was performed in 90% of randomized
      patients. At early and elective restudy (mean 4.2 months), the mean +/- SD
      difference in minimal lumen diameter between the postangioplasty and follow-up
      measurement was -0.55 +/- 0.58 mm for the no heparin group and -0.43 +/- 0.59 mm
      for the heparin group (p = NS). Clinical events during the follow-up period did
      not differ significantly between groups: fatal myocardial infarction (1 patient
      in each group), coronary bypass grafting (5 patients in each group), repeat
      angioplasty (12 in the no heparin, 6 in the heparin group), angina at 4-month
      assessment (33% in the no heparin, 32% in the heparin group). CONCLUSIONS: Long
      term treatment with high dose subcutaneous heparin (12,500 IU twice daily) for 4
      months did not favorably influence angiographic or clinical outcome after
      coronary angioplasty.

PMID- 7560624
TI  - Angioplasty of complex lesions in ischemic rest angina: results of the
      Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial.
AB  - OBJECTIVES: This study sought to analyze the role of complex lesion morphology on
      the acute results of angioplasty. BACKGROUND: Acute complications of angioplasty
      are higher in unstable than in stable angina. The unstable culprit lesion is
      usually complex, indicative of plaque disruption and thrombus formation. Previous
      nonrandomized studies have shown that the presence of intracoronary thombus
      increases morbidity after coronary angioplasty. The role of complex morphology in
      coronary angioplasty outcome was studied in a prespecified subgroup analysis of a
      large multicenter coronary angioplasty trial. METHODS: The results of coronary
      angioplasty from the Thrombolysis and Angioplasty in Unstable Angina (TAUSA)
      trial were analyzed. This large trial randomized 469 patients in double-blinded
      manner to receive either intracoronary urokinase or placebo during coronary
      angioplasty of the culprit lesion in ischemic rest angina with or without recent
      infarction. The study presented here analyzes in detail the results of coronary
      angioplasty in complex versus simple lesions in the urokinase and placebo groups.
      Complex lesions were defined before angioplasty by a core laboratory as having
      one or more of the following: irregular borders, overhanging edges, ulcerations
      or intraluminal filling defects proximal or distal to the lesion. RESULTS: Of the
      469 patients, 458 had identifiable culprit lesions, of which 245 were complex and
      213 were simple. Complex lesions were associated with a higher abrupt closure
      rate than simple lesions (10.6% vs. 3.3%, respectively, p < 0.003). Patients with
      complex lesions also had higher recurrent in-hospital angina (p < 0.02) and
      emergent bypass surgery (p < 0.02). Further analysis of complex lesions revealed
      that abrupt closure was particularly high in the urokinase group (15.0% vs 5.9%
      for the placebo group, p < 0.03), and most abrupt closures were thrombotic.
      Composite clinical end points were also significantly higher with complex lesions
      and urokinase. In the placebo group, complex lesions had a higher abrupt closure
      rate as well as postcoronary angioplasty filling defects, but clinical end points
      were not significantly different. CONCLUSIONS: Complex lesions before coronary
      angioplasty increase acute complication rates after coronary angioplasty.
      Urokinase as administered in the TAUSA trial had significant adverse effects,
      especially in complex lesions. However, even in the placebo arm, complex lesions
      were associated with higher complication rates than simple lesions. Newer
      antithrombotic measures that particularly target the platelet may eventually
      decrease complication rates in these lesions.

PMID- 7560625
TI  - Dual-chamber pacing with a short atrioventricular delay in congestive heart
      failure: a randomized study.
AB  - OBJECTIVES: This prospective study assessed the initial hemodynamic effects and
      long-term clinical benefits of dual-chamber pacing with a short atrioventricular
      (AV) delay in patients with chronic heart failure who had no traditional
      indication for pacemaker implantation. BACKGROUND: Dual-chamber pacing with a
      short AV delay has been proposed as a nonpharmacologic treatment for drug
      refractory heart failure. Both initial and long-term hemodynamic as well as
      functional benefits have been reported. All previous studies have used an AV
      delay of 100 ms. Despite encouraging results, these previous studies have been
      anecdotal and uncontrolled. METHODS: This double-blind, randomized, crossover
      trial included 12 subjects with chronic congestive heart failure despite optimal
      medical therapy. Patients were required to be in sinus rhythm with no evidence of
      significant bradyarrhythmias. On the day after implantation of a dual-chamber
      pacemaker, invasive hemodynamic measurements were made at varying AV delays
      between 100 and 200 ms. Patients were then randomized to either dual-chamber
      pacing with a 100-ms AV delay or backup mode (VVI at 40 beats/min). After 4 to 6
      weeks, crossover to the other pacing mode was programmed. RESULTS: Hemodynamic
      measurements on the day after pacemaker implantation demonstrated no benefit of
      pacing with any AV delay compared with intrinsic conduction. At the optimal AV
      interval for each patient, neither cardiac output (4.5 +/- 1.5 vs 4.7 +/- 1.6
      liters/min [mean +/- SD]) nor wedge pressure (16 +/- 10 vs 17 +/- 8 mm Hg)
      improved significantly from baseline measurements during intrinsic conduction.
      The long-term pacing protocol was completed in nine patients. Ejection fraction
      was 16 +/- 6% with dual-chamber (VDD mode) pacing and 18 +/- 4% in backup mode (p
      = NS). No patient had an increase in ejection fraction by > or = 5% with VDD
      pacing, nor did any patient improve in New York Heart Association functional
      class with short AV delay dual-chamber pacing. Also, there were no significant
      reductions in body weight or diuretic requirements during this pacing period.
      CONCLUSIONS: Dual-chamber pacing with a short AV delay does not improve
      hemodynamic and clinical status or ejection fraction measured on the day after
      pacemaker implantation in patients with chronic congestive heart failure. Routine
      use of pacemaker therapy with a short AV delay aas a primary treatment of heart
      failure in patients without standard arrhythmic indications is unwarranted.

PMID- 7560626
TI  - Dilated cardiomyopathy: to pace or not to pace.

PMID- 7560627
TI  - Low intensity exercise training in patients with chronic heart failure.
AB  - OBJECTIVES: The present study was designed to evaluate whether a specific program
      of low intensity exercise training may be sufficient to improve the exercise
      tolerance of patients with chronic heart failure. BACKGROUND: Recent studies have
      shown that exercise training can improve exercise tolerance in patients with
      stable chronic heart failure, mainly through peripheral adaptations. These
      changes have been observed with exercise regimens at intensities of 70% to 80% of
      peak oxygen uptake and > 8 weeks. METHODS: We studied 27 patients (23 men, 4
      women; mean [+/- SD] age 57 +/- 6 years) with mild chronic heart failure. We
      classified patients into two groups: trained group and untrained group. The
      trained group underwent a low intensity (40% of peak oxygen uptake) training
      program three times/week for 8 weeks. The untrained group performed no exercise.
      RESULTS: An increase in peak oxygen uptake (17%, p < 0.0001), lactic acidosis
      threshold (20%, p < 0.0002) and peak work load (21%, p < 0.0002) were obtained in
      the trained group only. Cardiac output and stroke volume were unchanged. A high
      correlation was found between the increases in peak oxygen uptake and volume
      density of mitochondria of vastus lateralis muscle (r = 0.77, p < 0.0002).
      CONCLUSIONS: Patients with stable chronic heart failure can achieve significant
      improvement in functional capacity from a low intensity exercise training
      regimen. The mechanism responsible for this favorable effect involves an increase
      in mitochondrial density, which reflects an improvement in oxidative capacity of
      trained skeletal muscles.

PMID- 7560628
TI  - Heart rate variability in patients with mild to moderate heart failure: effects
      of neurohormonal modulation by digoxin and ibopamine. The Dutch Ibopamine
      Multicenter Trial (DIMT) Study Group.
AB  - OBJECTIVES: This study assessed the effects of digoxin and ibopamine on variables
      of heart rate variability in relation to neurohormonal activation. BACKGROUND:
      Analysis of heart rate variability can be used to study the autonomic dysfunction
      that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter
      Trial, patients with heart failure were found to have increased neurohormonal
      activation with placebo therapy but not with digoxin and ibopamine therapy.
      METHODS: We studied 59 patients with mild to moderate heart failure (mean [+/-
      SEM] age 60 +/- 1 years, mean ejection fraction 0.30 +/- 0.01). Patients were
      randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine
      (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy
      consisted of furosemide (up to 80 mg). RESULTS: After 3 months, plasma
      norepinephrine levels had increased with placebo, whereas they decreased with
      digoxin (+31 vs. -60 pg/ml, respectively, p < 0.01). With ibopamine,
      nonsignificant decrease was observed (-27 pg/ml, p = 0.10). All variables of
      heart rate variability showed a deterioration in the placebo group. With digoxin,
      the percent differences between successive RR intervals > 50 ms (pNN50) increased
      (+ 1.7 +/- 0.9%, p < 0.01), along with absolute and normalized high frequency
      power (+ 40 +/- 33 ms2, p < 0.05 and + 2.4 +/- 1.7%, p < 0.01, respectively).
      These changes were observed during daytime hours only and were most pronounced in
      patients with the most impaired baseline heart rate variability. With ibopamine,
      nonsignificant trends similar to the changes with digoxin were observed.
      CONCLUSIONS: In patients with early stages of heart failure, digoxin may prevent
      a progressive deterioration in heart rate variability, whereas ibopamine does not
      show statistically significant effects. The changes in heart rate variability
      with digoxin parallel an observed decrease in neurohormonal activation. Digoxin
      apparently enhances cardiac vagal tone in the setting of neuroendocrine
      activation.

PMID- 7560629
TI  - Digoxin or flecainide for prophylaxis of supraventricular tachycardia in infants?
AB  - OBJECTIVES: This study compared the safety and efficacy of digoxin and flecainide
      in the prophylaxis of supraventricular tachycardia in infants. BACKGROUND:
      Recurrence of supraventricular tachycardia in infants is common. Digoxin is the
      conventional drug of first choice for prophylaxis, but its efficacy has not been
      tested in a controlled clinical trial, and there is no consensus on the drug of
      choice when digoxin is ineffective. METHODS: We reviewed retrospectively the
      records of all infants with supraventricular tachycardia due to atrioventricular
      (AV) reentry admitted to our hospital between January 1986 and December 1993.
      RESULTS: Thirty-nine infants presented with sustained AV reentrant tachycardia at
      age 1 to 330 days (median 12). Intravenous flecainide was required to maintain
      immediate control in six patients who were then treated with oral flecainide. The
      other 33 patients were treated with oral digoxin. There was no recurrence of
      tachycardia in 14 (42%) of the 33 patients (95% confidence interval [CI] 25% to
      61%). In the other 19 patients (58%) (95% CI 39% to 75%), digoxin was replaced by
      oral flecainide because of multiple recurrence of tachycardia. Full control was
      achieved in all 19 of these patients (100%) (95% CI 82% to 100%) and in 5 of the
      6 patients treated with both intravenous and oral flecainide. Thus, overall,
      flecainide was effective in 24 (96%) of 25 patients (95% CI 80% to 100%).
      CONCLUSIONS: Comparison with previous natural history studies suggests that
      digoxin is ineffective in the prophylaxis of supraventricular tachycardia. Oral
      flecainide was effective in a small number of infants, with no adverse effects
      (95% CI 0% to 12%), and may now be preferred as the primary prophylactic agent.

PMID- 7560631
TI  - Statement on self-monitoring of peak expiratory flows in the investigation of
      occupational asthma. Subcommittee on Occupational Allergy of European Academy of
      Allergy and Clinical Immunology.

PMID- 7560630
TI  - The levoatriocardinal vein: morphology and echocardiographic identification of
      the pulmonary-systemic connection.
AB  - OBJECTIVES: This study considers the array of pulmonary-systemic connections made
      by the levoatriocardinal vein. The primary and associated lesions that play a
      role in forming this vein are examined, and echocardiography is discussed as a
      method for its rapid identification. BACKGROUND: The levoatriocardinal vein is a
      pulmonary-systemic connection that provides an alternative egress for pulmonary
      venous blood in left-sided obstructive lesions. It is thought to result from the
      persistence of anastomotic channels that connect the capillary plexus of the
      embryonic foregut to the cardinal veins. Only 12 cases of levoatriocardinal vein
      have been reported since its first description in 1926. A comprehensive
      description of the morphology and echocardiographic identification of this lesion
      has been unavailable because of its rarity. METHODS: A retrospective study was
      performed in 13 patients with a levoatriocardinal vein from the University of
      California, San Francisco. Echocardiographic findings were compared with those
      obtained by angiography or at necropsy. In addition, the details of 12 previously
      published case reports were reviewed. Age at presentation, primary obstruction to
      pulmonary venous return, integrity of the atrial septum and origin and drainage
      of the levoatriocardinal vein were compared. RESULTS: Patient age at presentation
      was < 2 years, with most patients presenting before age 6 months. Variations of
      the hypoplastic left heart syndrome accounted for the majority of primary defects
      encountered, although multiple but less severe left-sided lesions were seen. The
      atrial septum was functionally intact in most patients. The levoatriocardinal
      vein, defined echocardiographically, originated predominantly from the smooth
      walled left atrium and drained to the superior vena cava or innominate vein;
      however, variations of this pattern existed. CONCLUSIONS: As a physiologic
      entity, the levoatriocardinal vein provides a mechanism for decompression of
      pulmonary venous return primarily in patients with left ventricular inflow
      obstruction. A levoatriocardinal vein is thought to form when the atrial septum
      fails to provide an alternate egress for left atrial blood. However, when a
      septal defect or alternative shunt occurs in conjunction with a levoatriocardinal
      vein, the clinical presentation may be postponed. Echocardiography provides a
      rapid, noninvasive modality for identifying the pulmonary-systemic connection,
      which may masquerade as the vertical vein in anomalous pulmonary venous
      connection or act as an occult source of left to right shunting in patients
      undergoing surgery for hypoplastic left heart syndrome.

PMID- 7560632
TI  - Atopic dermatitis: the skin as a window into the pathogenesis of chronic allergic
      diseases.
AB  - This review has attempted to highlight several important advances in our
      understanding of the immunopathogenesis of AD. These include the observation that
      IgE has a multifunctional role in the pathogenesis of allergic inflammation.
      Aside from its involvement in IgE-mediated degranulation of mast cells and
      basophils, it is also involved in the activation of macrophage/monocytes and the
      stimulation of TH2 cells. Recent data also suggest that the pattern of cytokine
      expression in AD depends on the acuity or duration of the skin lesion. The acute
      onset of skin inflammation in AD is associated with a predominance of T
      lymphocytes and IL-4 gene expression. In chronic AD, macrophage and eosinophil
      activation dominate. These effector cells overexpress IL-5, IL-10, GM-CSF, and
      PGE2, all of which may contribute to the persistence of this disease. Although AD
      is not simply "asthma of the skin," similar principles may be operative in these
      associated atopic diseases. Both involve local infiltration of IL-4--and IL-5-
      secreting TH2-like cells, and both show pathologic evidence of epithelial damage,
      which likely serves to amplify tissue inflammation. In the case of AD,
      keratinocyte damage caused by scratching or microbial agents (e.g., S. aureus) is
      accompanied by the release of proinflammatory cytokines. In the case of asthma,
      bronchial epithelial damage (e.g., damage caused by viruses or eosinophil
      cationic proteins) and cytokine release from airway epithelium are believed to
      play an important role in the pathogenesis of airway inflammation. The
      observation that chronic AD is associated with lichenification and dermal
      fibrosis, which are only slowly responsive to topical corticosteroids, is
      somewhat analogous to the recent concerns over airway remodeling (e.g.,
      subepithelial airway fibrosis) is asthma and the finding that early intervention
      with inhaled corticosteroids is needed for optimal responses. Differences in the
      clinical manifestations of disease in these important target organs are likely to
      lie in their distinct resident cells, environment exposures that occur in the
      skin but not the lung, and the immune response to allergen sensitization of
      specialized lymphoid systems. Although the major focus of research in allergy to
      date has been on understanding of generic mechanisms underlying IgE regulation
      and action, it is well known that although IgE responses are necessary, they are
      not sufficient to account for the chronicity or tissue specificity of different
      allergic diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7560633
TI  - Diagnosis of soybean-induced asthma.
AB  - BACKGROUND: The role of soybean dust as a causal agent of asthma has been clearly
      established since the Barcelona asthma epidemics in the 1980s. The large number
      of patients who were first seen with asthma symptoms during those epidemics
      provided an excellent opportunity to study the possibilities of different
      diagnostic tests. OBJECTIVE: This study was designed to evaluate the usefulness
      of the skin test and amplified ELISA technique for quantifying specific IgE in
      the diagnosis of soybean asthma. PATIENTS AND RESULTS: Ninety epidemic asthmatic
      patients and 95 nonepidemic asthmatic patients were studied 2 years after the
      last epidemic. Results of prick tests and ELISAs for specific IgE with hull and
      dust extracts showed a significant difference between the two groups of patients
      (p < 0.001). Sensitivity and specificity of glycerinated prick test with hull
      extract in epidemic asthmatic patients were 57.7% and 95.3%, respectively, and
      ELISA values were 56.6% and 93.7%, respectively. Similar results were obtained
      with dust extracts. CONCLUSION: Glycerinated skin prick tests and ELISAs with
      soybean hull and dust extracts have proved effective in the diagnosis of soybean
      asthma, even 2 years after the epidemics. Taking into account the sensitivity
      (90.5%) and specificity (93.7%) of ELISA test results for epidemic asthmatic
      patients found when the epidemic occurred, data from this study suggest that both
      tests may be very useful for the diagnosis of soybean dust-induced asthma.

PMID- 7560634
TI  - Chemical treatment of carpets to reduce allergen: comparison of the effects of
      tannic acid and other treatments on proteins derived from dust mites and cats.
AB  - BACKGROUND: Several chemical treatments have been recommended for reducing mite
      and other allergen levels in carpets, including the protein-denaturing agent
      tannic acid (TA). OBJECTIVE: We evaluated the efficacy of TA and other treatments
      on mite and cat allergens in carpets within houses. The effects of TA were
      assessed on Der p 1 and Der f 1, on group II mite allergens, and on the major cat
      allergen Fel d 1. METHOD: Carpet treatments tested were benzyl benzoate moist
      powder, a 3% TA spray, and two carpet cleaners (Host and Capture). Carpets were
      treated twice and dust samples collected on a biweekly basis for 8 weeks: these
      samples were extracted in saline solution alone. Additional studies evaluated the
      effects of TA on 17 carpets. Carpets were treated twice (on days 0 and 28) and
      samples collected on days 0, 1, 7, 14, 28, and 42. Eighteen carpets were
      untreated controls. Dust samples were extracted separately in both saline
      solution and in the presence of 5% bovine serum albumin. RESULTS: Benzyl benzoate
      and the two carpet cleaners reduced group 1 dust mite allergen concentrations in
      carpet dust. In addition, benzyl benzoate and TA reduced airborne group 1 mite
      allergens by more than 64%. Further studies showed that, in keeping with in vitro
      studies, TA inhibited the assay and bovine serum albumin abrogated this effect.
      Significant reductions after treatment occurred only for Der f 1 and group 2 dust
      mite allergens (p = 0.005 and p = 0.035, respectively). However, for all mite
      allergens the percentage changes after treatment were significant when compared
      with untreated carpets (p < 0.005 for Der f 1 and group 2 mite, p < 0.02 for Der
      p 1) but not for cat allergen (p > 0.3). The results suggested that repeated
      application of TA was necessary to maintain reduced allergen concentrations.
      CONCLUSION: Carpet treatments can reduce mite-derived allergen levels in airborne
      and carpet dust. However, the effects do not appear to be maintained for long
      periods, are not dramatic, and are different for different allergens.

PMID- 7560635
TI  - Albumin and immunoglobulin levels in nasal secretions of patients with nasal
      polyps treated with endoscopic sinus surgery and topical corticosteroids.
AB  - BACKGROUND: Nasal polyposis is principally treated by surgery, which may be
      combined with administration of topical corticosteroids to postpone or prevent
      recurrences. OBJECTIVE: In this study endoscopic sinus surgery and subsequent use
      of topical corticosteroids (budesonide) for 1 year was evaluated. METHODS:
      Clinical data of 41 patients with nasal polyps were evaluated, and their nasal
      secretions were compared with those of 26 healthy persons (control subjects).
      RESULTS: The patients had much higher initial total protein, albumin, IgM,
      secretory IgA (S-IgA) (p < 0.001 for all), and IgG concentrations (p < 0.05) than
      the control subjects. Treatment resulted in a significant decrease of S-IgA (p <
      0.001) within 6 months. IgM and IgG concentrations decreased more slowly (p <
      0.001 and p < 0.05 at 1 year, respectively). IgE levels decreased, but we could
      not demonstrate significance. Relative to total protein levels, the albumin and S
      IgA levels decreased within 6 months (p < 0.005 and p < 0.001, respectively). The
      excretion of all proteins remained higher in patients than in the control
      subjects, even after 1 year of topical corticosteroid treatment. Clinical
      evaluation showed slightly higher S-IgA levels in patients with an IgE-mediated
      allergy than in those without such a condition, and the recurrence rate was
      highest in the former group (75% vs 48%). CONCLUSION: The data support the
      hypothesis that inflammatory reactions in the nasal mucosa play a role in the
      pathogenesis of nasal polyps but also suggest an additional causative factor.

PMID- 7560636
TI  - Immunologic cross-reactivity among cereal grains and grasses in children with
      food hypersensitivity.
AB  - BACKGROUND: Because of a lack of clinical data from food challenges, allergists
      often recommend dietary restriction of all cereal grains in patients with
      sensitivity to at least one grain. OBJECTIVES: The purposes of this study were to
      assess the degree of intrabotanical cross-reactivity among cereal grains and
      related grasses, to better define the prevalence of multiple grain
      hypersensitivity, and to define the protein fractions associated with wheat
      hypersensitivity. METHODS: One hundred forty-five patients evaluated by food
      challenges and skin prick tests were divided into three groups: group 1, cereal
      grain and grass allergies; group 2, wheat allergy alone; and group 3, grass
      allergy alone. Fifteen patients were further selected from groups 1 to 3. Sodium
      dodecylsulfate--polyacrylamide gel electrophoresis and immunoblot analyses were
      performed on six grains and four related grasses with sera from these patients.
      RESULTS: Only 21% of patients had symptomatic reactivity as determined by food
      challenge; 80% had reactivity to only one grain. As determined by immunoblot
      analyses, patients in groups 1 and 2 showed extensive cross-reactivity (within
      each group) among grains but little cross-reactivity among grasses, whereas
      patients in group 3 showed cross-reactivity between the grains and grasses.
      Patients with wheat allergy had specific IgE binding to wheat fractions 47 kd and
      20 kd, bands not recognized by patients with grass allergy. CONCLUSIONS:
      Clinically insignificant cross-reactivity exists among cereal grains and grasses;
      therefore, elimination of all grains from the diet of a patient with grain
      allergy is unwarranted. Further purification and characterization of the 47 kd
      and 20 kd wheat fractions is needed to provide more specific in vitro testing.

PMID- 7560637
TI  - Isolation and preliminary characterization of cDNA encoding American cockroach
      allergens.
AB  - BACKGROUND: Two prominent proteins of 78 and 72 kd in Cr-PI have been found to be
      the major allergens of American cockroach (Periplaneta americana). METHODS: A
      lambda gt22A cDNA library generated from messenger RNA of American cockroach was
      packaged into Escherichia coli Y1090(r-) and initially screened with rabbit
      polyclonal antiserum raised to crude extract of American cockroach (CRa-A).
      RESULTS: Twenty-nine anti-CRa-A-positive clones were isolated, and 11 clones were
      recognized by rabbit anti-Cr-PI and reactive with IgE antibodies of atopic serum
      pool. Among these 11 clones, eight were recognized by murine anti-Cr-PI
      monoclonal antibodies. Four clones (C7, C8, C12, and C29) were found to contain
      inserts of 2.6 kilobases (kb), and clones C5 and C20 were found to contain
      inserts of 2.4 kb. The remaining clones (C13, C23, C25, C28, and C35) were found
      to contain inserts of 1.8, 1.6, 2.5, 1.7, and 0.9 kb, respectively. Clones C12,
      C20, C13, and C28 were selected, subcloned into the expression pET vectors, and
      used to transform, E. coli BL21(DE3). Immunoblot analyses of clones C12, C20,
      C13, and C28 with anti-Cr-PI monoclonal antibodies revealed fusion proteins with
      molecular weights of 78 and 50 kd, and 43 kd, 54 kd, and 46 kd, respectively.
      However, among those fusion proteins only those with molecular weights of 78, 72,
      54, and 46 kd were able to bind human specific IgE antibodies. CONCLUSIONS: The
      cDNA clones are expected to code for the major and principal allergens of
      American cockroach, and recombinant allergens may therefore be valuable for
      diagnostic and therapeutic purposes.

PMID- 7560638
TI  - Mast cell number and phenotype in chronic idiopathic urticaria.
AB  - BACKGROUND: Increased levels of histamine have been previously demonstrated in
      patients with chronic idiopathic urticaria. OBJECTIVE: The purpose of the study
      was to determine whether increased numbers of mast cells are present in lesional
      skin from such patients. METHODS: Mast cells have been quantified in lesional (n
      = 11) and nonlesional (n = 9) skin from patients with chronic idiopathic
      urticaria and compared with site-matched skin from healthy control subjects (n =
      10). Mast cells were identified by using a sensitive, double-labeling
      immunohistochemical technique with specific monoclonal antibodies to mast cell
      tryptase and chymase and quantified under light microscopy. RESULTS: No
      significant differences in mast cell numbers from lesional, nonlesional, or
      control skin were observed (p > 0.1, Student's t test). In both patients with
      urticaria and control subjects, more than 99% of cutaneous mast cells contained
      tryptase and chymase. CONCLUSIONS: These data indicate that increased skin
      histamine in chronic idiopathic urticaria is not caused by increased mast cells
      and may alternatively reflect an increase in histamine content per mast cell,
      enhanced mast cell activation, or recruitment of basophils into skin in patients
      with chronic idiopathic urticaria.

PMID- 7560639
TI  - Residual antigenicity of hypoallergenic infant formulas and the occurrence of
      milk-specific IgE antibodies in patients with clinical allergy.
AB  - BACKGROUND: Milk protein hydrolysates are frequently used in milk substitutes for
      children with cow's milk allergy. However, cases of hypersensitivity to
      commercially available hypoallergenic infant formulas based on milk protein
      hydrolysates have been reported. OBJECTIVE: Our purpose was to determine the
      immunologic response of milk protein-specific IgE and IgG in the serum of
      patients allergic to cow's milk against four commercially available
      hypoallergenic milk protein hydrolysates and eight infant formulas. METHODS:
      Antibody levels in patients' serum and milk protein-specific residual
      antigenicity of the hypoallergenic products were determined by indirect and
      competitive ELISA. RESULTS: Patients allergic to cow's milk had IgE and IgG
      antibodies to several protein fractions of cow's milk; intraindividual and
      interindividual variation in the concentrations of these antibodies was
      considerable. In general, IgE and IgG residual antigenicity of individual milk
      proteins in the hypoallergenic products was lower compared with that of the
      intact milk protein, but immunoreactive epitopes could still be detected in all
      products. Their number varied considerably among the individual milk proteins and
      also differed among products. CONCLUSIONS: The individual sensitization pattern
      of the patient allergic to cow's milk and the milk protein-specific residual
      antigenicity might be considered as possible laboratory predictors of adverse
      reactions to hypoallergenic products. Their determination could be a useful
      preclinical screening test for pediatricians to select a formula adapted to the
      individual patient.

PMID- 7560640
TI  - Effect of interleukin-5 and granulocyte-macrophage colony stimulating factor on
      in vitro eosinophil function: comparison with airway eosinophils.
AB  - Eosinophils are hypothesized to be crucial in the development of allergic airway
      inflammation; however, the actual mechanisms that determine their inflammatory
      activity are still largely undefined. To investigate the factors that regulate
      eosinophil function in allergic airway disease, we have previously used segmental
      bronchoprovocation with allergen to study ex vivo eosinophil function. To
      determine whether the functional changes associated with airway eosinophils
      obtained by bronchoalveolar lavage 48 hours after antigen challenge are caused by
      exposure to airway-generated cytokines, normodense blood eosinophils were
      cultured in vitro with recombinant human interleukin-5 (IL-5) or granulocyte
      macrophage colony stimulating factor (GM-CSF). The effect of cytokine exposure
      was then evaluated on selected cell functions. In vitro incubation with these
      cytokines for 24 hours significantly increased eosinophil membrane expression of
      CD18 and CD11b compared with culture in medium alone or eosinophils obtained by
      bronchoalveolar lavage. N-formyl-methionyl-leucyl-phenylalanine-stimulated
      superoxide anion generation was slightly but significantly enhanced by incubation
      with IL-5 but not with GM-CSF. In addition, spontaneous adhesion to human
      umbilical vein endothelial cell monolayers was increased after exposure to both
      IL-5 and GM-CSF. However, activated adhesion was enhanced only by culture with IL
      5 and stimulation with N-formyl-methionyl-leucyl-phenylalanine. The magnitude of
      functional changes after in vitro preincubation of eosinophils with these
      cytokines did not achieve levels of superoxide anion and adhesion noted with
      airway eosinophils obtained after segmental bronchoprovocation with allergen.
      These observations raise the possibility that the contribution of IL-5 and GM-CSF
      to phenotypic changes of airway eosinophils is principally to enhance survival
      and expression of adhesion proteins. These data also suggest that, in addition to
      the generation of proinflammatory cytokines, other factors contribute to
      phenotypic changes in eosinophils as they migrate from the blood to the airway.

PMID- 7560641
TI  - Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas
      in infants with multiple food protein intolerance.
AB  - BACKGROUND: Many infants with cow's milk protein intolerance have adverse
      reactions to soy, casein and whey hydrolysate formula and to other foods. The
      recent development of Neocate, a hypoallergenic, nutritionally complete infant
      formula composed of individual amino acids and other nutrients, has enabled these
      infants to be stabilized. OBJECTIVE: We observed the effect of food challenges in
      infants with reported hypersensitivity to hypoallergenic formulas. METHODS:
      Eighteen infants (median age, 7 1/2 months) were given Neocate formula for 2
      months and then underwent a 7-day double-blind placebo-controlled challenge with
      the formula previously best tolerated. RESULTS: In 12 of the 18 infants
      irritability, vomiting, diarrhea, and/or eczema flares developed during the
      formula challenge. In two patients symptoms developed immediately, but in the
      remainder adverse reactions evolved within 7 days (range, 4 to 7 days). Adverse
      reactions were to soy formula (six patients), whey hydrolysate (two), and casein
      hydrolysate (four). When infants were 12 months of age, parents reported adverse
      reactions after the ingestion of other low allergen foods (median, six; from a
      panel of 10 such foods). CONCLUSION: A group of infants with late-onset adverse
      reactions to soy, extensively hydrolyzed casein, and whey formulas and to other
      foods has been identified. Neocate formula proved to be an effective substitute
      formula for these patients.

PMID- 7560642
TI  - Type I skin reactivity to native and recombinant phospholipase A2 from honeybee
      venom is similar.
AB  - Phospholipase A2 is the major allergen in honeybee venom. Recombinant
      phospholipase A2 was produced in prokaryotes and tested for its biologic activity
      by intracutaneous skin testing with serial 10-fold dilutions in comparison with
      native and deglycosylated phospholipase A2 in patients allergic to bee venom.
      Linear regressions of the log of the wheal area versus the log of the allergen
      concentration were calculated for all allergens in each patient. The relative
      allergenic potency of the various preparations was analyzed by comparing the
      linear regressions. Native phospholipase A2 was about 10 times more potent than
      whole bee venom. None of 58 patients allergic to bee venom was missed by testing
      with native phospholipase A2 alone. This allergen and deglycosylated native
      phospholipase A2 resulted in similar skin reactions, indicating that the sugar
      residues were of little relevance for IgE-binding in the patients tested. Native
      phospholipase A2 also had relative potency similar to that of recombinant
      refolded phospholipase A2, whereas recombinant nonrefolded phospholipase A2 had
      almost no biologic activity in skin testing. These results demonstrate in vivo
      activity of the recombinant bee venom allergen phospholipase A2. Although correct
      refolding is a prerequisite for type I skin reactivity, glycosylation seems to be
      less important.

PMID- 7560643
TI  - Immunodeficiency with hyperimmunoglobulinemia M in two female patients is not
      associated with abnormalities of CD40 or CD40 ligand expression.
AB  - The immunologic defect in X-linked immunodeficiency and hyperimmunoglobulinemia M
      (HIM) are related to defective expression of the CD40 ligand (CD40L). We have
      studied two female patients with HIM to evaluate the role of CD40/CD40L in the
      pathogenesis of impaired immunoglobulin switching. In addition to recurrent
      infections characteristic of humoral immunodeficiencies, the two patients had
      chronic hepatitis caused by type C virus. Phenotypic characterization of
      peripheral blood mononuclear cells showed a similar picture in both patients,
      with a reduction in the absolute numbers of CD4 cells and increased numbers of
      CD8 and CD3/DR cells. B cells (CD19+) were reduced in one patient, but CD40 was
      expressed on all CD19+ cells in both patients. The expression of CD40L was normal
      on peripheral blood mononuclear cells from the two patients with HIM on both
      resting and stimulated cells. The combination of anti-CD40 and cytokines
      (interleukin-2, interleukin-4, and interleukin-10) was able to restore
      proliferative capacity to anti-IgM. Peripheral blood mononuclear cells from the
      two patients with HIM showed a high spontaneous production of IgM in vitro and no
      production of IgG or IgE. Our data suggest that the defect of isotype switching
      in female patients with HIM is not related to defective expression of the
      CD40/CD40L receptor system. A possible role for chronic hepatitis C virus
      infection in the pathogenesis of the disease is suggested by the detection of
      specific production of anti-hepatitis C virus IgM.

PMID- 7560644
TI  - No relationship between skin-infiltrating TH2-like cells and allergen-specific
      IgE response in atopic dermatitis.
AB  - More than 500 CD4+ T-cell clones (TCCs) derived from the skin of eight patients
      with atopic dermatitis (AD), two patients with nonatopic dermatologic disorders,
      two patients with allergic rhinitis, and one healthy nonatopic donor were
      analyzed for both their pattern of cytokine production and their antigen
      specificity. The proportions of TCCs from patients with AD producing interleukin
      4 in response to stimulation with phorbol 12-myristate 13-acetate plus anti-CD3
      antibody were higher, whereas the proportions of interferon-gamma--producing TCCs
      were lower than those of control subjects. In two patients with AD, the majority
      of TCCs had a TH2/TH0-like phenotype, whereas in six patients with AD a TH1/TH0
      like phenotype was prevalent. TCCs with a TH2/TH0-like phenotype were also
      isolated from the healthy skin of two patients with allergic rhinitis and one
      nonatopic donor. In contrast, no TH2-like TCCs were derived from the skin of the
      two patients with dermatologic disorders of nonallergic origin. No unambiguous
      correlations was found between the proportions of TCCs producing interleukin-4 or
      interferon-gamma (or of TCCs with TH2- or TH1-like profile) and the level of
      total serum IgE, suggesting that CD4+ T cells infiltrating the atopic skin do not
      play a major role in the production of serum IgE antibodies. When TCCs from five
      patients with AD were examined for their specificity, the proportions of allergen
      specific (Dermatophagoides pteronyssinus and Lol p 1) clones were consistently 6%
      or lower even in patients with high titers of ryegrassor D. pteronyssinus
      specific IgE antibodies. Because similar percentages of allergen-specific TCCs
      were found in skin from two healthy control subjects, the role of aeroallergens
      in favoring and maintaining skin lesions in patients with AD remains unclear.

PMID- 7560645
TI  - Altered glucocorticoid receptor binding in atopic dermatitis.

PMID- 7560646
TI  - Recurrent allergic reactions to latex in a hospitalized pediatric patient.

PMID- 7560647
TI  - Amphotericin B: emergency challenge in a neutropenic, asthmatic patient with
      fungal sepsis.

PMID- 7560648
TI  - Interleukin-5 production by T lymphocytes in atheroembolic disease with
      hypereosinophilia.

PMID- 7560649
TI  - Severe anaphylactic reaction to topical administration of framycetin.

PMID- 7560650
TI  - Skin test responses to latex in an allergy and asthma clinic.

PMID- 7560651
TI  - Skin testing with foods.

PMID- 7560652
TI  - Is there a dose-response relationship between exposure to indoor allergens and
      symptoms of asthma?

PMID- 7560653
TI  - Mite allergen (Der p 1) concentration in houses and its relation to the presence
      and severity of asthma in a population of Sydney schoolchildren.
AB  - House dust mite (HDM) allergen exposure and its relation to HDM allergy and
      asthma was assessed in a case-control study conducted over three seasons in 74
      Sydney schoolchildren, 33 of whom were allergic to HDM and 12 of whom had current
      asthma. In each season histamine inhalation tests and skin prick tests were
      performed, symptom questionnaires were administered, and dust samples were
      collected. The mean concentrations of HDM allergen (in micrograms of Der p 1 per
      gram of fine dust) were: bed, 38.9 (95% confidence interval [CI], 31.8 to 47.5);
      bedroom floor, 22.4 (95% CI, 18.3 to 27.5); and lounge room floor, 13.7 (95% CI,
      10.7 to 17.6). The mean of the highest allergen concentration in each house was
      51.0 (95% CI, 43.2 to 60.1). All but two subjects had at least one site in all
      seasons with an HDM allergen concentration greater than 10 micrograms/gm, the
      proposed threshold for asthma symptoms. Subjects with allergy to HDM, symptoms of
      asthma, or airway hyperresponsiveness did not have higher HDM allergen
      concentrations in their house. In this study we were unable to test hypotheses
      concerning proposed thresholds for risk of sensitization and for risk of asthma
      symptoms because virtually all subjects were exposed to HDM allergen levels above
      the proposed thresholds.

PMID- 7560654
TI  - Quantitative assessment of exposure to dog (Can f 1) and cat (Fel d 1) allergens:
      relation to sensitization and asthma among children living in Los Alamos, New
      Mexico.
AB  - BACKGROUND: Our objective was to identify the allergens associated with asthma
      among schoolchildren in an area of the United States where dust mite growth is
      expected to be poor. Los Alamos, N.M., was chosen because it has low rainfall and
      is at high altitude (7200 feet) making it very dry. One hundred eleven children
      (12 to 14 years old) from the middle school who had been previously classified
      according to bronchial hyperreactivity to histamine (BHR) were studied. METHODS:
      Sera were assayed for IgE antibodies to mite, cat, dog, cockroach, Russian
      thistle, and grass pollen, with both CAP system fluoroimmunoassay (Kabi
      Pharmacia, Uppsala, Sweden) and conventional RAST. Allergens were measured in
      dust samples from 108 homes with two-site assays for mite (Der p 1 and Der f 1),
      cat (Fel d 1), dog (Can f 1), and cockroach (Bla g 2). RESULTS: Concentrations of
      dog and cat allergens were elevated in almost all houses with pets but were also
      high in a significant proportion of the houses without pets. Levels of mite
      allergen were less than 2 micrograms/gm in 95% of the houses, and cockroach was
      undetectable in all but two of the houses. Among the 21 with BHR who had
      symptoms, 67% had IgE antibody to dog and 62% had IgE antibody to cat. For these
      allergens IgE antibody was strongly associated with asthma (p < 0.001). By
      contrast, the presence of IgE antibody to mite, cockroach, or grass pollen was
      not significantly associated with asthma. CONCLUSION: The high prevalence of IgE
      antibody to cat and dog allergens among these children is in keeping with the
      presence of cat and/or dog allergen in most of the houses. Furthermore,
      sensitization (as judged by IgE antibodies) to cat and dog allergens was strongly
      associated with asthma. On the other hand, no clear relationship was found
      between sensitization or symptoms and the current level of allergen in individual
      houses. The results show that in this mite-and cockroach-free environment
      sensitization to domestic animals was the most significant association with
      asthma.

PMID- 7560655
TI  - Work-related late asthmatic response induced by latex allergy.
AB  - BACKGROUND: The occupational uses of latex gloves may be associated with asthma.
      Hypersensitivity to latex has been shown to be IgE-mediated. The asthmatic
      reaction to latex is usually early; however, the natural history of latex asthma
      is still unknown. OBJECTIVE: The purposes of this study were to investigate
      asthmatic responses induced by natural rubber latex and to assess the long-term
      respiratory consequences of latex-induced asthma after removal from exposure.
      METHODS: This report describes the clinical and immunologic study of six nurses
      with work-related respiratory and skin disorders induced by the use of latex
      gloves. To determine whether the symptoms induced by latex gloves were IgE
      mediated, we assessed latex IgE antibody levels by skin prick tests (SPTs) and
      RASTs with latex extracts. To confirm work-related latex reactions, we assessed
      respiratory symptoms, skin reactions, and FEV1 after a glove exposure test and an
      inhalation provocation test with latex gloves. All subjects were followed up for
      7 months to 7 years after the first observation. RESULTS: All subjects had
      positive SPT and RAST responses to latex extracts, positive double prick test
      responses to latex gloves, and negative SPT responses to cornstarch and common
      allergens. Ten atopic and 10 nonatopic control subjects had negative SPT
      responses to latex and cornstarch extracts and negative double prick test
      responses to latex gloves. In three subjects latex allergy was associated with
      allergy to fruit (banana and chestnut). After the glove exposure test, four of
      six subjects had contact urticaria, all had rhinoconjunctivitis, and two had a
      late asthmatic response. The inhalation provocation test was performed on four
      subjects: all had rhinoconjunctivitis, two had urticaria and late asthmatic
      response, and one had laryngeal edema. A late asthmatic response was recorded in
      four subjects. Three subjects continued to have chronic asthma, and four subjects
      had increased nonspecific bronchial responsiveness 7 months to 7 years after
      being assigned to duties not involving latex gloves. CONCLUSIONS: This study of
      six nurses shows that latex is a potential cause of occupational asthma,
      rhinoconjunctivitis, and urticaria-angioedema. Latex seems to include antigens
      that elicit IgE-mediated hypersensitivity and may cause a late asthmatic
      reaction. Occupational asthma caused by latex may lead to permanent respiratory
      disability, even after removal from exposure.

PMID- 7560656
TI  - Systemic reactions to the Samsum ant: an IgE-mediated hypersensitivity.
AB  - BACKGROUND: In the United Arab Emirates the sting of the Pachycondyla
      sennaarensis ant (PSA) causes allergic reactions in certain persons. It is a
      common problem and is becoming a public health hazard. Up to now the diagnosis
      has been based only on the history, because the mechanism of the reaction was not
      yet established. OBJECTIVE: The aim of our study was to prepare an allergenic
      extract that would be used for skin tests and to prepare a reagent for specific
      IgE titration. Results of both skin tests and specific IgE were to be compared
      with the clinical history. METHODS: We studied 31 patients with anaphylactic
      reactions and performed clinical examinations, skin tests, and specific IgE
      antibody titrations. A control group of 22 subjects were also studied. RESULTS:
      In 30 of 31 patients (97%) findings of PSA skin tests and/or specific IgE were
      positive. In the control groups PSA skin test results were negative in 86% and
      negative for specific IgE in 68%. CONCLUSION: The study shows that the mechanism
      of the reaction to the sting of the PSA is a type I IgE-mediated hypersensitivity
      and that the diagnosis can now be confirmed by skin tests and specific IgE
      determination.

PMID- 7560657
TI  - The prevalence of Dermatophagoides mite allergen in Colorado homes utilizing
      central evaporative coolers.
AB  - OBJECTIVE: The prevalence of mite allergen was studied in homes in which the
      indoor relative humidity may be increased by use of an evaporative cooler.
      METHODS: Colorado homes in which central evaporative coolers are used and control
      homes were evaluated. ELISAs with monoclonal antibodies specific for Der p 1 and
      Der f 1 were performed on dust samples from each home in May and August. Indoor
      relative humidity and temperatures were recorded daily. RESULTS: May samples did
      not show significant levels of mite allergen ( < 2 micrograms/gm dust). Of the
      August samples, 48 of 95 samples from homes with evaporative coolers (50.5%) had
      levels of Der p 1 and Der f 1 of 2 micrograms/gm dust or greater, but only 5 of
      95 control samples (5.2%) had levels of 2 micrograms/gm dust or greater (p <
      0.00001). Twelve of 19 homes with evaporative coolers (63%) were positive for
      mite allergen. Five of 19 (26%) control homes were positive (p < 0.05). The homes
      with evaporative coolers had average indoor relative humidity of 51% or greater:
      control homes had average relative humidity of less than 45%. CONCLUSION:
      Altering the indoor environment by raising indoor relative humidity through use
      of evaporative coolers leads to conditions that may facilitate Dermatophagoides
      survival.

PMID- 7560658
TI  - Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic
      subjects.
AB  - OBJECTIVE: Cross-sensitivity between aspirin and acetaminophen in aspirin
      sensitive asthmatic patients has been reported with frequencies ranging from 0%
      to 29%. The relationship is dose-dependent for acetaminophen challenges, ranging
      between 300 and 100 mg. METHODS: To determine the prevalence of cross-sensitivity
      to high-dose acetaminophen, we performed single-blind acetaminophen oral
      challenges with 1000 mg and 1500 mg in 50 aspirin-sensitive asthmatic patients
      and in 20 non-aspirin-sensitive asthmatic control subjects. RESULTS: Overall, 17
      of 50 (34%) of aspirin-sensitive asthmatic patients reacted to acetaminophen in
      doses of 1000 to 1500 mg (95% confidence interval: 20% to 49%). By contrast, none
      of the 20 non-aspirin-sensitive asthmatic patients reacted to acetaminophen (95%
      confidence interval: 0% to 14%). This difference was highly significant (p =
      0.0013), supporting the hypothesis that cross-sensitivity between aspirin and
      acetaminophen is unique in aspirin-sensitive asthmatic patients. CONCLUSION:
      Although high-dose ( > 1000 mg) acetaminophen cross-reactions with aspirin were
      significant with respect to frequency (34%), such reactions included easily
      reversed bronchospasm in only 22%, and were generally mild. We recommended that
      high doses of acetaminophen (1000 mg or greater) should be avoided in aspirin
      sensitive asthmatic patients.

PMID- 7560659
TI  - Ethylene oxide allergy in children with spina bifida.
AB  - BACKGROUND: Allergic reactions to ethylene oxide (EtO-treated products have
      occurred in several children with myelomeningoceles. OBJECTIVE: The object of
      this study was to define the prevalence and significance of EtO-specific IgE
      among the children in our myelomeningocele clinic. METHODS: The study population
      comprised three groups: children clinic. METHODS: The study population comprised
      three groups: children with myelomeningoceles, chronically ill controls (defined
      as children who had undergone at least three major operations), and well-child
      controls. Serum specimens were collected from each child, and a commercially
      available ELISA designed to identify IgE directed against both EtO and latex was
      performed on the specimens. RESULTS: Seventeen of 75 (23%) children with
      myelomeningoceles had antibodies directed against EtO, as did 1 of 26 (4%)
      chronically ill controls. None of the 25 well controls had detectable levels of
      anti-EtO IgE. Children with antibodies directed against EtO were more likely to
      be atopic (p = 0.007) and to have a shunt (p = 0.021) and were markedly more
      likely to have antibodies directed against latex (p = 0.001). On average they had
      undergone more shunt revisions and other operations than had children without
      anti-EtO antibodies. CONCLUSION: During the period of study no child had
      anaphylaxis thought to have been due to EtO exposure.

PMID- 7560660
TI  - Diagnostic validation of specific IgE antibody concentrations, skin prick
      testing, and challenge tests in chemical workers with symptoms of sensitivity to
      different anhydrides.
AB  - BACKGROUND: The diagnostic possibilities of sensitization to various acid
      anhydrides are limited because of the lack of standardized allergens for the
      different test systems. This makes the diagnosis of IgE-mediated sensitization
      caused by occupational exposure difficult. METHODS: We prepared conjugates of
      human serum albumin with phthalic, maleic, trimellitic, and pyromellitic
      anhydrides to be used for IgE estimation by enzyme-allergosorbent test, skin
      prick tests, and nasal and bronchial challenge tests. Nine anhydride workers, who
      complained of various respiratory symptoms, were studied. RESULTS: Of the nine
      workers, four had immediate-type skin test responses to one or more conjugates.
      All four subjects had elevated IgE concentrations in addition to two other
      workers. Three of six nasal challenges and four of nine bronchial challenges
      resulted in positive responses. All but one of the positive nasal or bronchial
      test responses were associated with elevated IgE levels. The seven positive
      challenge test results included five positive skin test responses. On the other
      hand, in all but two of the subjects with negative challenge test results, no
      specific IgE could be detected. In these two subjects the negative results were
      associated with low levels of IgE, and in one, with the absence of asthma. None
      of the results of tests with unconjugated anhydrides were positive. CONCLUSIONS:
      Anhydrides investigated in this study can induce IgE-mediated hypersensitivity,
      which can be diagnosed by using the respective human serum albumin in estimation
      of specific IgE and in skin, nasal, and bronchial challenge tests. Estimation of
      IgE was demonstrated to be more sensitive than skin prick testing.

PMID- 7560661
TI  - Effect of solution and suspension type aerosol of formoterol on tremor response
      and airways in patients with asthma.
AB  - BACKGROUND: Aerosol delivery and deposition to the oropharynx and the lungs have
      been found to be different for solution-type and suspension-type metered-dose
      aerosols used for treatment of asthma. We investigated possible differences in
      clinical effects between solution and suspension metered-dose formoterol
      aerosols. METHODS: A total of 24 patients with asthma (forced expiratory volume
      in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24
      micrograms) of formoterol solution and suspension so that we could investigate
      the immediate tremor, airway, and cardiovascular responses in a randomized,
      double-blind, crossover trial. Fenoterol suspension aerosol (400 micrograms) was
      used for comparison (single-blind, poststudy, nonrandomized administration).
      Fenoterol (400 micrograms) as a rescue medication was inhaled after 120 minutes
      on each of the 5 study days. RESULTS: The order of mean (+/- SEM) maximum tremor
      acceleration was as follows: 12 micrograms formoterol solution (67.92 +/- 4.54 cm
      x sec-2) < 24 micrograms solution (73.46 +/- 4.51 cm x sec-2) < 12 micrograms
      suspension (80.87 +/- 5.08 cm x sec-2) < fenoterol (84.13 +/- 4.21 cm x sec-2) <
      24 micrograms formoterol suspension 88.54 +/- 6.26 cm x sec-2). Maximum increase
      in specific airway conductance ranged from 0.48 +/ 0.03 to 0.55 +/- 0.04 sec-1 x
      kPa-1 for all drugs (p > 0.05). No change in cardiovascular parameters occurred
      (p > 0.05). CONCLUSION: No difference in the bronchial response to either
      formulation of formoterol was found. Tremor response to suspension aerosol (24
      micrograms > 12 micrograms) was higher than that to solution aerosol (24
      micrograms > 12 micrograms), indicating possible differences in systemic
      absorption because of a different deposition pattern. Rescue medication
      demonstrated systemic effects on tremor that were additive to those of
      formoterol.

PMID- 7560662
TI  - Cross refractoriness between bradykinin and hypertonic saline challenges in
      asthma.
AB  - BACKGROUND: Repeated inhalation of bradykinin and hypertonic saline leads to
      refractoriness of the bronchoconstrictor response in asthma. It is not known
      whether cross-refractoriness exists between these stimuli. OBJECTIVE: We
      postulated that repeated bradykinin and hypertonic saline bronchial challenges
      might reduce the airway response to subsequent hypertonic saline and bradykinin
      challenges, respectively. METHODS: Eleven atopic asthmatic subjects underwent two
      concentration-response studies, separated by 1 hour, with either inhaled
      histamine or bradykinin. After recovery, a hypertonic saline challenge was
      performed. During the next phase, nine subjects underwent two concentration
      response studies, separated by 1 hour, with hypertonic saline. After recovery, a
      bradykinin challenge was performed. RESULTS: On the histamine study day, the mean
      provocative volume of agonist required to produce 20% drop in forced expiratory
      volume in 1 second (PD20) hypertonic saline was 220.7 L (+/- 42.7 L) and this was
      not significantly different from that measured at baseline. On the bradykinin
      study day, the geometric mean provocative concentration of agonist required to
      produce a 20% drop in forced expiratory volume in 1 second (PC20) was 0.39 mg/ml
      (0.01 to 11.73 mg/ml) for the first test and significantly higher at 1.38 mg/ml
      (0.01 to > 16.0 mg/ml) for the second test (p = 0.006). The hypertonic saline
      PD20 increased significantly from a baseline of 159.2 L (+/- 27.3 L) to 377.6 (+/
      64.7 ) (p = 0.003). On the hypertonic saline study day, the mean PD20 was 152.8
      L for the first test, and 337.7 L for the second test (p = 0.01). PC20 bradykinin
      increased significantly from a baseline of 0.57 to 2.56 mg/ml (p = 0.02). A
      significant correlation was found between loss of response to bradykinin and to
      hypertonic saline (rs, 0.63 and 0.76). CONCLUSION: Refractoriness produced by
      repeated exposure of the airways to bradykinin and hypertonic saline results in
      loss of responsiveness to hypertonic saline and bradykinin respectively,
      suggesting a shared mechanism for refractoriness produced by these stimuli.

PMID- 7560663
TI  - Cromolyn versus nedocromil: duration of action in exercise-induced asthma in
      children.
AB  - Cromolyn sodium (10 mg), nedocromil sodium (4 mg), and placebo, all delivered by
      a metered dose inhaler, were compared in their efficacy and duration of action in
      preventing exercise-induced asthma in children. After a screening test was
      performed, 13 patients with asthma performed standard exercise tests 20 minutes
      and 140 minutes after drug inhalation in a randomized, double-blind, crossover
      study. Both drugs were significantly more protective than placebo after 20
      minutes, but no significant difference was seen between cromolyn sodium and
      nedocromil sodium. No difference between active drugs and placebo was found 140
      minutes after inhalation. At these clinically recommended doses both cromolyn
      sodium and nedocromil sodium provide equal protection against exercise-induced
      asthma, and the duration of action of both lasts for less than 2 hours.

PMID- 7560664
TI  - Decreased frequency of interferon-gamma- and interleukin-2-producing cells in
      patients with atopic diseases measured at the single cell level.
AB  - BACKGROUND: Recently, diminished interferon-gamma (IFN-gamma) and increased
      interleukin (IL-4 production in peripheral blood mononuclear cells (PBMCs) from
      atopic patients have been described by several groups, measured as total cytokine
      content in culture supernatants. These studies suggested a predominance of TH2
      like cells producing large amounts of IL-4 in atopic patients. It is not clear
      whether the reported cytokine imbalances are the result of an alteration in the
      distribution of specific T-cell subsets or whether intrinsic dysregulation in
      cytokine production is a characteristic of atopic individuals. OBJECTIVE: This
      study examined the production of IFN-gamma, and IL-2 in PBMCs from atopic
      patients at the single cell level with the use of freshly isolated lymphocytes.
      METHODS: We recently described a flow cytometric assay in which three-color
      analysis was used to study the production of a cytokine of interest in a T-cell
      subpopulation defined by two cell surface markers. PBMCs from 23 atopic patients
      and 14 control subjects were stimulated with phorbol ester and ionomycin for 5
      hours. PBMCs from seven patients and seven control subjects were also cultured
      with immobilized anti-CD3 antibodies for 24 hours. Cells were fixed, made
      permeable, and stained for intracellular cytokines in combination with cell
      surface markers CD3, CD8, and CD45RO. Cytokine-producing cells were analyzed by
      gating on T-cell subsets. RESULTS: IFN-gamma-producing cells were significantly
      decreased (p < 0.05) in CD4+ T cells but not in CD8+ T cells of atopic patients.
      CD45R0+ and CD45R0-T cells showed a decreased proportion of IFN-gamma-producing
      cells (p < 0.05 and p < 0.01, respectively). IL-2 production was diminished in
      all T-cell subsets (p < 0.01). The number of IL-4-producing cells was not
      elevated, and such cells were exclusively found in the CD45RO+ T cells. Analysis
      of culture supernatants of sorted CD45RO+ T cells for IL-4 and IFN-gamma
      production confirmed these results. CONCLUSION: Our findings provide evidence
      that a reduced IFN-gamma production in atopic patients is due to an intrinsic
      defect selectively found in the CD4+ T cells. Because IL-2 production was
      markedly decreased but IL-4 production was unchanged, our data demonstrate a
      deficiency in the ability of atopic T cells to produce TH1-like cytokines on
      stimulation with phorbol ester, ionomycin, or anti-CD3 monoclonal antibodies.

PMID- 7560665
TI  - Histochemical and functional characteristics of metachromatic cells in the nasal
      epithelium in allergic rhinitis: studies of nasal scrapings and their dispersed
      cells.
AB  - BACKGROUND: In allergic rhinitis, metachromatic cells in the nasal epithelium
      increase in number and are thought to play an important role in nasal allergic
      manifestation. METHODS: To determine immunohistochemical and functional
      characteristics of the metachromatic cells, nasal scrapings and their dispersed
      cells from patients with perennial allergic rhinitis were studied. RESULTS:
      Eighty-three percent of all metachromatic cells in dispersed cell preparations
      were tryptase-positive mast cells (MCT), 10% were tryptase-chymase-positive cells
      (MCTC), and 7% were negative (n = 10). The mean histamine chymase-positive cells
      (MCTC), and 7% were negative (n = 10). The mean histamine content per
      metachromatic cell was 1.9 +/- 2 pg. The histamine content and histamine release
      from nasal surface scrapings of patients sensitized with mite antigen were
      strongly correlated with the level of serum IgE antibody for mite antigen. The
      net histamine release from nasal scraping was antigen-dose-dependent (1:2 x 10(7)
      to 1:2 x 10(3) dilution), and the antigen stimulated release of up to 17% of cell
      associated histamine within 5 to 7 minutes. Histamine release from nasal
      scrapings induced by calcium ionophore A23187 was up to 21% of cell-associated
      histamine within 2 to 4 minutes, but no histamine release was stimulated by
      compound 48/80, substance P, or poly-L-lysine. Histamine release from nasal
      scrapings was inhibited 46% (10(-5) mol/L) to 96% (10(-4) mol/L) by quercetin and
      58% (10(-4) mol/L) to 72% (10(-3) mol/L) by sodium cromoglycate. CONCLUSIONS:
      These findings show the predominant characteristics of mast cells in the nasal
      epithelium in allergic rhinitis, and this information may be useful in relation
      to a therapeutic approach.

PMID- 7560666
TI  - Evidence for distinct cytokine expression in allergic versus nonallergic chronic
      sinusitis.
AB  - BACKGROUND: The purpose of this study was to characterize the relationship
      between tissue cytokine expression and the cellular infiltrate present in chronic
      hyperplastic sinusitis with nasal polyposis (CHS/NP) and to compare the
      immunopathology and cytokine profile of patients with allergy versus patients
      without allergy. METHODS: Nasal polyp tissue samples from 12 patients with CHS/NP
      and nasal turbinate biopsy specimens from 10 normal control patients were
      examined for the expression of interleukin (IL)-4, IL-2, and interferon (IFN)
      gamma cytokine messenger RNA (mRNA) species by in situ hybridization. These data
      were analyzed in conjunction with data previously reported for the cytokine mRNA
      species granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5
      and the immunocytochemical profile of the inflammatory cell infiltrate. Patients
      with allergy were distinguished from those without allergy on the basis of
      allergy skin tests. RESULTS: Tissue eosinophilia was a prominent feature of both
      allergic and nonallergic CHS/NP and correlated in both subgroups with the density
      of GM-CSF and IL-3 mRNA+ cells. In comparison with normal controls, patients with
      allergic CHS/NP had significantly higher CHS/NP had significantly higher tissue
      densities of GM-CSF, IL-3, IL-4, and IL-5 (p < or = 0.025). In contrast, patients
      with nonallergic CHS/NP had significantly higher tissue densities of GM-CSF, IL
      3, and IFN-gamma (p < or = 0.001). The allergic and nonallergic subgroups showed
      distinct cytokine profiles with the most distinguishing cytokines of the allergic
      subgroup being IL-4 (p = 0.001) and IL-5 (p = 0.017) and of the nonallergic
      subgroup being IFN-gamma (p = 0.004). Furthermore, patients with allergic CHS/NP
      showed an increased density of CD3+ T lymphocytes compared with either controls
      or patients with nonallergic CHS/NP (p = 0.03). The density of CD3+ T lymphocytes
      was the only significant difference between patients with allergic and
      nonallergic CHS/NP. A clinical history of aspirin sensitivity was strongly
      correlated with nonallergic CHS/NP, as well as the nonallergic CHS/NP profile of
      cytokines, including IFN-gamma. CONCLUSION: We conclude that distinct mechanisms
      of eosinophilia exist in patients with allergic versus nonallergic CHS/NP. The
      allergic mechanism involves production of TH2-type cytokines, including GM-CSF,
      IL-3, IL-4, and IL-5, by infiltrating T lymphocytes. The nonallergic mechanism
      remains unknown but does involve production of GM-CSF, IL-3, and IFN-gamma.
      However, nonallergic eosinophilia is independent of IL-4 and IL-5, cytokines that
      contribute to tissue eosinophilia in allergic inflammation. Aspirin sensitivity
      is strongly correlated with nonallergic CHS/NP and production of the nonallergic
      CHS/NP profile of cytokines, including IFN-gamma.

PMID- 7560667
TI  - Hydrocortisone sodium succinate does not cross-react with aspirin in aspirin
      sensitive patients with asthma.
AB  - BACKGROUND: Bronchospasm after intravenous hydrocortisone treatment has been
      reported in some patients with aspirin-sensitive respiratory disease. OBJECTIVE:
      This study was designed to determine the prevalence of sensitivity to
      hydrocortisone among patients with aspirin-sensitive respiratory disease.
      METHODS: We performed double-blind, placebo-controlled challenges with aspirin
      and 100 mg of hydrocortisone sodium succinate administered intravenously in 53
      subjects. RESULTS: Forty-five of the 53 subjects (85%) undergoing oral aspirin
      challenge experienced respiratory reactions to aspirin. Forty-four of these 45
      patients had neither naso-ocular, cutaneous, nor respiratory reactions to
      hydrocortisone sodium succinate. One aspirin-sensitive subject had bronchospasm
      and a naso-ocular reaction to hydrocortisone sodium succinate and a naso-ocular
      reaction with minimal bronchospasm to methylprednisolone sodium succinate. After
      desensitization to aspirin, and while receiving maintenance aspirin therapy, this
      subject again reacted to hydrocortisone sodium succinate with bronchospasm and
      naso-ocular reaction. CONCLUSION: We conclude that aspirin-sensitive patients
      with asthma are not preferentially sensitive to hydrocortisone and that
      hydrocortisone sodium succinate does not cross-react or cross-desensitize with
      aspirin.

PMID- 7560668
TI  - In vitro lymphocyte proliferation with milk and a casein-whey protein hydrolyzed
      formula in children with cow's milk allergy.
AB  - Discordant results have been reported about the role of lymphocyte proliferation
      assays in patients with cow's milk allergy. We studied the peripheral blood
      mononuclear cell response of 10 children with cow's milk allergy by means of a
      lymphocyte proliferation test to determine the diagnostic value of this assay,
      the clinical tolerance of a new therapeutic hydrolyzed formula, and the evolution
      of lymphocyte proliferation after 3 months of a cow's milk-free diet with the
      hydrolyzed formula. The lymphocyte proliferation at the time of diagnosis in the
      patients with cow's milk allergy was not statistically different from the results
      in the control group. The proliferation test performed after 3 months of diet
      with the hydrolyzed formula and restriction of cow's milk protein showed that the
      cellular proliferation remained globally the same compared with the proliferation
      at the time of diagnosis. The hydrolyzed formula proteins induced a lower
      cellular proliferation than milk proteins in patients with cow's milk allergy.
      Our results suggest that the lymphocyte proliferation test cannot be recommended
      for diagnostic purposes. However, in patients with cow's milk allergy the
      proliferation test affirmed the absence of immunogenicity of the hydrolyzed
      formula because it induced no significant T-cell activation.

PMID- 7560669
TI  - Recurrent anaphylaxis caused by Anisakis simplex parasitizing fish.

PMID- 7560670
TI  - Generalized urticaria caused by sesame seeds with negative prick test results and
      without demonstrable specific IgE antibodies.

PMID- 7560671
TI  - Cockroaches and mites share the same beds.

PMID- 7560674
TI  - Better drug trials: reply.

PMID- 7560672
TI  - IgE antibody to gelatin in children with immediate-type reactions to measles and
      mumps vaccines.

PMID- 7560673
TI  - Inhaled beclomethasone and bone metabolism in young asthmatic children: a six
      month study.

PMID- 7560675
TI  - Bronchial asthma caused by onion.

PMID- 7560676
TI  - Allergen immunotherapy in young children.

PMID- 7560677
TI  - Washington 'train wreck' derails ADA issues.

PMID- 7560678
TI  - Variety is still the spice of a healthful diet. A look at proposed revisions for
      the 1995 Dietary Guidelines for Americans. Dietary Guidelines Advisory Committee.

PMID- 7560679
TI  - Securing the inclusion of medical nutrition therapy in managed care health
      systems.

PMID- 7560680
TI  - The Healthy Eating Index: design and applications.
AB  - OBJECTIVE: To develop an index of overall diet quality. DESIGN: The Healthy
      Eating Index (HEI) was developed based on a 10-component system of five food
      groups, four nutrients, and a measure of variety in food intake. Each of the 10
      components has a score ranging from 0 to 10, so the total possible index score is
      100. METHODS/SUBJECTS: Data from the 1989 and 1990 Continuing Survey of Food
      Intake by Individuals were used to analyze the HEI for a representative sample of
      the US population. STATISTICAL ANALYSES PERFORMED: Frequencies, correlation
      coefficients, means. RESULTS: The mean HEI was 63.9; most people scored neither
      very high nor very low. No one component of the index dominated the HEI score.
      People were most likely to do poorly in the fruit, saturated fat, grains,
      vegetable, and total fat categories. The HEI correlated positively and
      significantly with most nutrients; as the total HEI increased, intake for a range
      of nutrients also increased. DISCUSSION/CONCLUSIONS: The HEI is a useful index of
      overall diet quality of the consumer. The US Department of Agriculture will use
      the HEI to monitor changes in dietary intake over time and as the basis of
      nutrition promotion activities for the population.

PMID- 7560681
TI  - Eating disorders: current nutrition therapy and perceived needs in dietetics
      education and research.
AB  - OBJECTIVE: Research was conducted to obtain a profile of nutrition therapy
      currently in practice for patients with anorexia nervosa, bulimia nervosa, and
      anorexia/bulimia (mixed diagnosis) and to identify the areas of dietetics
      education and research regarding eating disorders that need more attention.
      DESIGN: A cross-sectional correlational survey was conducted by mailing a
      questionnaire composed of open- and closed-ended questions to US dietitians who
      work with patients who have eating disorders. SAMPLE: Of 199 dietitians selected
      from a list of 495 representing all geographic areas of the United States, 117
      responded. The list was obtained from a national referral network for eating
      disorders. STATISTICAL ANALYSIS: chi 2 Analysis was completed on all closed-ended
      answers. Pearson's correlation coefficient with a value of P < .05 was considered
      significant. RESULTS: Nutrition therapy administered varied among dietitians
      treating inpatients, outpatients, and both. Three community groups were
      identified as most important to reach for prevention of eating disorders: junior
      high school students, coaches, and parents. Crucial areas of research were
      perceived by 94 dietitians to be comparative effectiveness of techniques of
      medical nutrition therapy (n = 55) and of techniques of prevention (n = 26) and
      increased understanding of etiology in relation to identification of high-risk
      groups and prevention (n = 21). Dietitians desired further information on
      multiple topics related to eating disorders. APPLICATION: Medical nutrition
      therapy for eating disorders is a specialization that requires education and
      training beyond the minimum required for dietetic registration. Some of the
      techniques required are unique to this specialization due, in part, to the
      psychological nature of the disorders. All dietitians, however, must be able to
      recognize and refer patients with eating disorders; these skills must be included
      in basic undergraduate programs and internships. This study supports the need for
      more research concerning the outcomes of nutrition therapy and the effectiveness
      of prevention programs.

PMID- 7560682
TI  - Clinical nutrition management position: responsibilities and skill development
      strategies.
AB  - OBJECTIVE: To determine the duties of clinical nutrition managers, the factors
      associated with the performance of the duties, the job specifications for the
      position, and the skill development strategies used by clinical nutrition
      managers. DESIGN: Clinical nutrition managers from 700 randomly selected, acute
      care hospitals in the United States (with 300 or more beds) received a survey
      questionnaire. Respondents were asked to indicate performance or nonperformance,
      perceived importance, and methods used to develop skills for 54 duties related to
      clinical nutrition management. We requested additional information about position
      requirements, position characteristics, and demographic information. STATISTICAL
      ANALYSES PERFORMED: An 82% response rate with 67% usable responses (n = 472) was
      achieved. Frequencies for performance and nonperformance, mean importance, and
      frequencies for methods of skill development were determined for each duty. chi 2
      Analysis with P < .10 was used to determine if an association existed between
      performance of a duty and time allotted to the position, number of personnel
      supervised, and type of personnel supervised. RESULTS: This study validated 46 of
      the duties as responsibilities of practicing clinical nutrition manager. Three
      duties not validated were related to financial management. The duty performed
      least often was conducting research/investigative studies. The number and type of
      personnel supervised was found to influence performance of duties, but time
      allotted to position was not an influence. The major strategies used for skill
      development were continuing education, networking, work experience in clinical
      dietetics, work experience in management dietetics, and their present job.
      APPLICATIONS: These results can be used by clinical nutrition managers to assess
      the characteristics of their current position and develop a plan for enhancing
      their scope of responsibility. The identification of duties actually performed by
      clinical nutrition managers can also be used to develop standards of practice
      with performance indicators and recommended thresholds. Information regarding the
      skill development strategies of clinical nutrition managers can be used by
      practitioners to enhance their current skills and knowledge and by others to
      prepare for career opportunities in clinical nutrition management.

PMID- 7560683
TI  - The play approach to learning in the context of families and schools: an
      alternative paradigm for nutrition and fitness education in the 21st century.
AB  - An alternative paradigm for nutrition and fitness education centers on
      understanding and developing skill in implementing a play approach to learning
      about healthful eating and promoting active play in the context of the child, the
      family, and the school. The play approach is defined as a process for learning
      that is intrinsically motivated, enjoyable, freely chosen, nonliteral, safe, and
      actively engaged in by young learners. Making choices, assuming responsibility
      for one's decisions and actions, and having fun are inherent components of the
      play approach to learning. In this approach, internal cognitive transactions and
      intrinsic motivation are the primary forces that ultimately determine healthful
      choices and life habits. Theoretical models of children's learning--the dynamic
      systems theory and the cognitive-developmental theory of Jean Piaget--provide a
      theoretical basis for nutrition and fitness education in the 21st century. The
      ultimate goal is to develop partnerships of children, families, and schools in
      ways that promote the well-being of children and translate into healthful life
      habits. The play approach is an ongoing process of learning that is applicable to
      learners of all ages.

PMID- 7560684
TI  - Dietary studies of children: the Bogalusa Heart Study experience.
AB  - For more than 20 years the Bogalusa Heart Study has been collecting data on
      children's dietary intakes in a biracial community. The macronutrient
      contribution of children's diets is similar to that in diets of adolescents: 13%
      of energy from protein, 49% from carbohydrate, and 38% from fat. As children get
      older, mean intakes of vitamins and minerals per 1,000 kcal decrease. Ten-year
      old children in 1987-1988 were 3 lb heavier than 10-year-olds in 1973-1974. Yet
      total energy intakes remained virtually the same from 1973 to 1988. The
      composition of macronutrients shifted over the 15-year period, with an increase
      in the percentage of energy from protein and carbohydrate and a decrease in the
      percentage of energy from total fat, particularly saturated fat. Dietary
      cholesterol intake also decreased as a result of a decrease in egg consumption.
      Although the diets of children changed positively from 1973 to 1988, more than
      75% of children consumed more total fat, saturated fat, and cholesterol than the
      recommended amounts. School meals had a major impact on the diets of children.
      School breakfast and lunch, together, contributed approximately 50% of the day's
      total intake of energy, protein, cholesterol, carbohydrate, and sodium. About 40%
      of daily total fat intake came from school breakfast and lunch. The diets of
      children in the Bogalusa study are similar to those reported in national studies
      of children. What might be different, however, are the types of foods consumed
      and their contribution to intakes of specific nutrients.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7560685
TI  - Does breakfast make a difference in school?
AB  - This article reviews selectively the literature on the effects of breakfast on
      cognition and school performance. The focus is on studies published in refereed
      journals after 1978 that tested those effects on well-nourished and nutritionally
      at-risk children. In at-risk subjects (defined by clinical history and
      anthropometry), a morning and overnight fast had adverse effects on cognition,
      particularly the speed of information retrieval in working memory. Contradictions
      in the data from different studies prevent definitive conclusions on whether well
      nourished children experience similar functional deficits. Nonetheless, available
      information suggests that brain function is sensitive to short-term variations in
      the availability of nutrient supplies. Moreover, well-conducted evaluations
      suggest that the availability of feeding programs in public schools throughout
      the academic year increases the probability that children will eat breakfast and
      improve their educational status.

PMID- 7560687
TI  - Food labels consistently underestimate the actual weights of single-serving baked
      products.

PMID- 7560686
TI  - Importance of dietary fiber in childhood.
AB  - Dietary fiber has important health benefits in childhood, especially in promoting
      normal laxation. Currently, children consume amounts of dietary fiber that appear
      to be inadequate for optimal health promotion and disease prevention. It is
      prudent to recommend that children older than 2 years of age increase dietary
      fiber intake to an amount equal to or greater than their age + 5 g/day. According
      to the "age + 5" rule dietary fiber intake would increase from 8 g/day at age 3
      years to 25 g/day by age 20 years. After age 20, dietary fiber levels of 25 to 35
      g/day are recommended. Dietary fiber intake should be increased gradually in
      childhood by increasing consumption of a variety of fruits, vegetables, legumes,
      cereals, and other whole-grain products. Although very high fiber intake in
      childhood could have adverse effects, the potential health benefits of a moderate
      increase in dietary fiber substantially outweigh the possible risks, especially
      in highly industrialized countries such as the United States. A safe range of
      dietary fiber intake for children may be between age + 5 and age + 10 g/day. This
      range is considered safe even for children and adolescents with marginal intakes
      of some vitamins and minerals; should provide enough dietary fiber for normal
      laxation; and may provide enough added dietary fiber to help prevent chronic
      diseases.

PMID- 7560688
TI  - Aminoglycosides lower serum magnesium concentrations in patients with cystic
      fibrosis: a retrospective study.

PMID- 7560689
TI  - Nutrition knowledge and behavioral assessment of participants of Aid for Families
      with Dependent Children: telephone vs mail data collection methods.

PMID- 7560690
TI  - Coordinated program directors: activities and perceptions about research, tenure,
      and promotion.

PMID- 7560691
TI  - Nutrition knowledge and attitudes of hotel and restaurant management students.

PMID- 7560692
TI  - Position of the American Dietetic Association: world hunger.

PMID- 7560693
TI  - Opportunities in commercial foodservice: the industry perspective.

PMID- 7560694
TI  - President's page: children--a small audience only in stature.

PMID- 7560695
TI  - Effects of resistance training on strength, power, and selected functional
      abilities of women aged 75 and older.
AB  - OBJECTIVE: To determine the effects of 12 weeks of progressive resistance
      strength training on the isometric strength, explosive power, and selected
      functional abilities of healthy women aged 75 and over. DESIGN: Subjects were
      matched for age and habitual physical activity and then randomly assigned into
      either a control or an exercise group. SETTING: The Muscle Function Laboratory,
      Royal Free Hospital School of Medicine, London. PARTICIPANTS: Fifty-two healthy
      women were recruited through local and national newspapers. Five dropped out
      before and seven (4 exercisers and 3 controls) during the study. Pre- and
      posttraining measurements were obtained from 20 exercisers (median age 79.5,
      range 76 to 93 years) and 20 controls (median age 79.5, range 75 to 90 years).
      INTERVENTIONS: Training comprised one supervised session (1 hour) at the Medical
      School and two unsupervised home sessions (supported by an exercise tape and
      booklet) per week for 12 weeks. The training stimulus was three sets of four to
      eight repetitions of each exercise, using rice bags (1-1.5 kg) or elastic tubing
      for resistance. The exercises were intended specifically to strengthen the
      muscles considered relevant for the functional tasks, but were not to mimic the
      functional measurements. No intervention was prescribed for the controls.
      MEASUREMENTS: Pre- and posttraining measurements were made for isometric knee
      extensor strength (IKES), isometric elbow flexor strength (IEFS), handgrip
      strength (HGS), leg extensor power (LEP), and anthropometric indices (Body
      impedance analysis, arm muscle circumference, and body weight). Functional
      ability tests were chair rise, kneel rise, rise from lying on the floor, 118-m
      self-paced corridor walk, stair climbing, functional reach, stepping up, stepping
      down, and lifting weights onto a shelf. Pre- and posttraining comparisons were
      made using analysis of variance or analysis of covariance (using weight as a
      covariate) for normally distributed continuous data and one-sided Fishers exact
      test (2 x 2 table) for discontinuous data. RESULTS: Improvements in IKES (mean
      change 27%, P = .03), IEFS (22%, P = .05), HGS (4%, P = .05), LEP/kg (18%, P =
      .05) were associated with training, but the improvement in LEP (18%, P = .11) did
      not reach statistical significance. There was an association between training and
      a reduction in normal pace kneel rise time (median change 21%, P = .02) and a
      small improvement in step up height (median 5%, P = .005). The other functional
      tests did not improve. CONCLUSIONS: Progressive resistance exercise can produce
      substantial increases in muscle strength and in power standardized for body
      weight in healthy, very old women. However, isolated increases in strength and
      LEP/kg may confer only limited functional benefit in healthy, independent, very
      old women.

PMID- 7560696
TI  - Bone density, vitamin D nutrition, and parathyroid hormone levels in women with
      dementia.
AB  - OBJECTIVE: To determine whether patients with dementia have reduced bone mass,
      altered vitamin D, or parathyroid hormone status. DESIGN: Survey. SETTING:
      University hospital outpatient department. PARTICIPANTS: Twenty women with DSM
      III-R mild dementia living in the community were compared with 40 cognitively
      normal community-dwelling women, matched for age, who had been recruited as part
      of studies in elderly twins. MEASUREMENTS: Bone density at the lumbar spine and
      neck of femur by dual-energy X-ray absorptiometry, intact serum PTH, and 25
      hydroxyvitamin D levels. MAIN RESULTS: There was no significant difference in
      bone density between the subjects with mild dementia and the age- and sex-matched
      controls. The intact PTH (mean +/- SD) in the demented subjects was 4.9 +/- 2.1
      pmol/L compared with 2.9 +/- 1.7 pmol/L in the twin controls (P < .01). The mean
      25-hydroxyvitamin D in the demented subjects was 61 +/- 33 nmol/L, whereas it was
      90 +/- 38 nmol/L in the twin controls (P < .01). CONCLUSIONS: We conclude that
      there were no significant differences in the bone density of community-dwelling
      women with mild dementia compared with normals. However, there were significant
      differences in parathyroid hormone and vitamin D levels between the two groups,
      suggesting that there is a high prevalence of subclinical hypovitaminosis D in
      demented women in the community.

PMID- 7560697
TI  - Determinants of functional abilities in dementia.
AB  - OBJECTIVES: To determine the extent to which selected variables within
      demographic, psychometric, and memory domains can predict functional abilities in
      dementia. DESIGN: Hierarchical regression analyses were employed to predict
      functional abilities, while controlling for disease severity, using the Mini
      Mental State Exam (MMSE). SETTING AND PARTICIPANTS: A total of 2368 inhabitants
      of Kungsholmen parish in Stockholm, Sweden, aged 75 years of age or older. Eighty
      one subjects with confirmed dementia (MMSE, M = 17.9; SD = 5.26) were selected
      from the study population. The mean age was 84.5 years (SD = 5.58), and 72% were
      female. MEASUREMENTS: Participants received a battery of standardized
      neuropsychological instruments and selected experimental tasks that measured
      visuospatial ability as well as primary and episodic memory. Self-care was
      assessed using the Katz index of activities of daily living (ADL); instrumental
      activities of daily living (IADL) were assessed through the primary caregiver,
      who responded to questions related to functional competence of the participant.
      RESULTS: Hierarchical regression procedures revealed that disease severity was
      the strongest predictor of ADL and IADL performance. Controlling for disease
      severity, a measure of visuoperception (Poppelreuter's figures) also made a
      significant contribution to the explanatory variance in both ADL and IADL
      function. Beyond disease severity and visuoperception, years of schooling and
      disease duration were marginally predictive of IADL performance. CONCLUSION: It
      is possible to predict functional abilities in dementia on the basis of
      individual difference variables. Multiple variables were initially correlated
      with ADL and IADL performance; however, after controlling for disease severity,
      visuoperception was the only predictor of ADL scores. In addition to
      visuoperception, IADL scores were also marginally predicted by education and
      disease duration. These findings highlight the importance of peripheral sensory
      processes in adaptive function in dementia. They also suggest that although many
      variables may be correlated with functional ability, their explanatory role,
      particularly with regard to self-care skills, is diminished in the presence of
      the disease.

PMID- 7560698
TI  - Does physical activity improve sleep in impaired nursing home residents?
AB  - OBJECTIVES: To determine if two physical activity programs of varying intensity
      would result in improved sleep among incontinent and physically restrained
      nursing home residents. DESIGN: Controlled trials of two physical activity
      programs. SETTING: Seven community nursing homes in the Los Angeles area.
      PARTICIPANTS: Residents were included if they had urinary incontinence or were
      physically restrained. Sixty-five subjects were studied. Mean age was 84.8 years,
      85% were female, mean length of residency in the nursing home was 19.9 months,
      and mean Mean Mini-Mental State Exam score was 13.1. INTERVENTION: The first
      physical activity program involved sit-to-stand repetitions and/or transferring
      and walking or wheelchair propulsion. These activities were performed every 2
      hours during the daytime, 5 days per week for 9 weeks. The second, less frequent
      physical activity program involved rowing in a wheelchair-accessible rowing
      machine plus walking or wheelchair propulsion once per day three times per week
      for 9 weeks. MEASUREMENTS: The physical function measures reported here include
      mobility endurance (maximum time walking or wheeling) and physical activity as
      measured by motion sensors (Caltrac). Nighttime sleep was estimated by wrist
      activity monitors. Nighttime sleep measures included total time asleep, percent
      sleep, average duration of sleep, and peak duration of sleep. Daytime sleep was
      measured by timed behavioral observations of sleep versus wakefulness performed
      every 15 minutes during the day. RESULTS: Nighttime sleep was markedly disrupted
      in both groups at baseline. Across all subjects at baseline, the average total
      sleep time was 6.2 hours and the percent sleep was 72.0%, but the average
      duration of sleep episodes was only 21.2 minutes and the peak duration of sleep
      episode averaged only 83.8 minutes. During the daytime, subjects were observed
      asleep during 14.5% of observations. Although there was improvement in mobility
      endurance in the intervention subjects compared with controls (MANOVA F = 4.36, P
      = .042), there were no differences in the night and day sleep measures at follow
      up testing. Even among a subgroup of intervention subjects who showed a 30% or
      greater improvement in mobility endurance, sleep did not improve at follow-up
      compared with baseline. CONCLUSION: This study supports our previous findings of
      marked sleep disruption in impaired nursing home residents. In addition, despite
      documented improvements in physical function with activity, we did not find
      improvements in sleep in the intervention versus control groups. These results
      suggest that increasing daytime physical activity alone is not adequate to
      improve sleep in impaired NH residents. Future efforts to improve sleep in this
      population should take into account the multifactorial nature of sleep
      disruption, including individual health problems that effect sleep and the
      disruptive nature of the nighttime NH environment.

PMID- 7560699
TI  - Admission health status differences of black and white indigent nursing home
      residents.
AB  - OBJECTIVE: To compare the health status of newly admitted lower socioeconomic
      status (SES) southern black (n = 81) and white (n = 53) nursing home residents.
      DESIGN: The study data were part of a larger prospective study on the health of
      newly admitted nursing home residents. SETTING: A 575-bed, government-funded
      nursing home providing care for indigent residents in a large southern city.
      PARTICIPANTS: Newly admitted black and white nursing home residents aged 60 and
      older. MEASUREMENTS: Mental status was measured using the Short Portable Mental
      Status Questionnaire, activities of daily living by Scaled Outcome Criteria, and
      medical status by medical diagnoses and medications. MAIN RESULTS: Blacks
      entering the nursing home were more cognitively and functionally impaired and had
      3.7 years less education than white residents, but average age was not
      significantly different for black and white residents. CONCLUSIONS: Many common
      health status measures showed no significant black-white differences for
      institutionalized older adults when region and SES were constants. However,
      mental status, self-care activities, and marital status were significantly
      different. These findings indicate a possible impact of lifelong poverty or low
      educational attainment on the increased disability of indigent black older
      adults. Black residents in our study had less spousal support to remain in the
      community.

PMID- 7560700
TI  - Sexual function of men ages 40 to 79 years: the Olmsted County Study of Urinary
      Symptoms and Health Status Among Men.
AB  - OBJECTIVES: Knowledge of male sexual function is somewhat limited because of a
      lack of current population-based data. This study provides information on sexual
      function and satisfaction in a population-based sample of men. METHODS: Men aged
      40 to 79 years (n = 2115) were selected randomly from the Olmsted County
      population for the baseline component of a prospective cohort study (the Olmsted
      County Study of Urinary Symptoms and Health Status Among Men) during 1989-1990.
      The men completed a self-administered questionnaire that included questions about
      sexual concerns, performance, satisfaction, drive, and erectile dysfunction.
      RESULTS: For all five sexual parameters queried, the prevalence of problems and
      dysfunction increased with age. A comparison of men aged 70 to 79 years with men
      aged 40 to 49 years suggested that older men were more worried about sexual
      function (46.6% vs 24.9%), had worsened performance compared with a year ago
      (30.1% vs 10.4%), expressed extreme dissatisfaction with sexual performance
      (10.7% vs 1.7%), had absent sexual drive (25.9% vs 0.6%), and reported complete
      erectile dysfunction when sexually stimulated (27.4% vs 0.3%). Logistic
      regression analyses suggested that sexual dissatisfaction was significantly
      associated with erectile dysfunction, decreased libido, and the interaction
      between erectile dysfunction and libido, but not age. CONCLUSIONS: These
      population-based cross-sectional data corroborate the previously reported age
      related decrease in sexual function. The age-related increase in dissatisfaction
      could, however, be accounted for primarily by the age-related increase in
      erectile dysfunction, decreased libido, and the interaction between erectile
      dysfunction and decreased libido.

PMID- 7560701
TI  - A cost and value analysis of two interventions with incontinent nursing home
      residents.
AB  - OBJECTIVE: More than half of nursing home residents suffer from urinary
      incontinence. These residents typically have long stays and, because of comorbid
      cognitive and physical impairments, have little hope of living again in a
      noninstitutional environment The value of interventions to change functional
      status of this chronically institutionalized population is often questioned. This
      paper explores this value issue in the context of two incontinence management
      interventions that have been shown to improve functional status: (1) Functional
      Incidental Training (FIT), and (2) Prompted Voiding (PV). The relative value of
      the different interventions for the nursing home population was estimated using
      paired preferences. DESIGN: The cost of two interventions (FIT and PV) that
      target incontinent nursing home residents was related to the value of these
      interventions as perceived by consumers of nursing home services. Both
      interventions decrease incontinence frequency, and one intervention also improves
      mobility endurance. PARTICIPANTS: Ninety incontinent nursing home residents
      received the intervention; 37 older nondemented board and care residents and 31
      family members of the nursing home residents provided estimates of the
      intervention's value. MEASUREMENT: The staff-time allocations involved in
      implementing both interventions were documented in more than 85 resident care
      episodes. These time data were converted to labor cost based on the cost of
      nursing aides who would actually implement the intervention. The value of each
      intervention was assessed by asking consumers to make choices between the
      intervention and its associated outcomes (such as increased dryness) and other
      nursing home services of known cost (e.g., moving to a private room). RESULTS:
      Both interventions had labor costs that were greater than "usual care" costs. The
      additional cost was estimated to be $4.31 per resident per day for PV and $6.42
      per resident per day for FIT if these programs were implemented from 7 AM to 7
      AM. Consumer preference data indicated that consumers preferred the FIT and PV
      outcomes to more expensive alternative services, calculated to cost $10.00 per
      day, often marketed to consumers, CONCLUSION: Consumers may prefer the FIT and PV
      interventions relative to the typical services often marketed to the nursing home
      consumer. The analysis completed in this paper suggests that both interventions
      have value for frail residents likely to live out their lives in a nursing home.

PMID- 7560702
TI  - Depression in a long-term care facility: clinical features and discordance
      between nursing assessment and patient interviews.
AB  - OBJECTIVE: Nurses commonly observe more depression than is diagnosed and treated
      in nursing homes. Accordingly, we aimed to describe the clinical features of
      untreated nursing home residents whom nurses identify as depressed and to compare
      nurse ratings of depressed nursing home residents with ratings from direct
      interviews and patient self-reports. DESIGN: Cross-sectional survey followed by
      semi-structured diagnostic interviews of depressed patients and their nurses.
      SETTING: A large academic, multi-level, long-term care facility. PARTICIPANTS:
      Thirty-seven patients aged 74-99 (mean age 88.4) whom nurses identified as having
      daily symptoms of depression. Subjects had Mini-Mental State Exam (MMSE) scores >
      10 (mean score 21.2), were not acutely or terminally ill, and were able to
      participate in an interview. MEASUREMENTS: DSM-III-R mood diagnoses and separate
      ratings of interviews with nurses and patients using the Cornell Scale for
      Depression. RESULTS: Nurses observed daily symptoms of depression in 110 of 495
      (22%) long-term care residents on units not reserved for advanced dementia. Of
      these 110 patients, 58 (53%) were not receiving antidepressants. Of 37 patients
      eligible for interviews, nine met criteria for major depression, 20 met criteria
      for another non-major depression diagnosis, and eight did not have a diagnosable
      mood disorder. Cornell scale ratings derived exclusively from interviews of
      nurses were similar across the three diagnostic groups (12.5, 9.9, and 9.5,
      respectively; P = .31; mean 10.5), whereas Cornell scale ratings from patient
      interviews differed among groups (15.9, 6.9, and 4.1, respectively; P < .001;
      mean 8.4). Correlation between nurse Cornell ratings and patient Cornell ratings
      was poor (r = .27), especially for patients with non-major forms of depression (r
      = -.20). MMSE and Cumulative Illness Rating Scale (CIRS-G) scores were similar in
      the three groups. CONCLUSIONS: Nurses frequently observed symptoms of depression
      in a long-term care setting, and many symptomatic patients were not being treated
      with antidepressants. In these patients, nurse-derived symptom ratings did not
      vary across DSM-III-R diagnostic categories and correlated poorly with ratings
      from direct patient interviews. These findings suggest that nurse caregivers may
      contribute important diagnostic information about non-major depression and raise
      questions about the application of standard diagnostic categories to late-life
      depression in the nursing home.

PMID- 7560703
TI  - Predictors of 2-year mortality among older male veterans on a geriatric
      rehabilitation unit.
AB  - OBJECTIVE: To determine if nutritional parameters and discharge setting are
      associated with mortality in older male veterans on a Geriatric rehabilitation
      unit (GRU). DESIGN: Two-year follow-up of sequential admissions to the GRU who
      had laboratory studies completed on admission to the acute hospital and on
      transfer to and discharge from the GRU. SETTING: University-affiliated VA medical
      center. PATIENTS: Eighty-three consecutive older male veterans admitted to the
      GRU. MEASUREMENT: Mortality during a period of 2 years post-discharge. MAIN
      RESULTS: In a univariate analysis, predictors of mortality were serum albumin
      level < or = 3.5 g/dL on admission to the GRU (P = .01), moderate or severe
      Nutritional Status Score (P = .03), discharge to a place other than home (P =
      .01), and use of antibiotics while on the GRU (P = .05). Discharge albumin
      remained the single significant predictor of mortality in a multivariate analysis
      (P = .005). CONCLUSIONS: Serum albumin is the strongest predictor of 2-year post
      hospitalization mortality of older patients cared for on a GRU. Other predictors
      were presence of infection, Nutritional Status Score of moderate or severe
      compromise, and discharge to a place other than home.

PMID- 7560704
TI  - Clinical trials in cognitively impaired older adults: home versus clinic
      assessments.
AB  - OBJECTIVE: To compare the reliability of instruments used in clinical trials
      involving cognitively impaired older adults when the instruments are administered
      in-home rather than in-clinic and to compare withdrawal rates is these two
      groups. DESIGN: This study was part of a larger n-of-1 clinical trial to
      investigate the efficacy and safety of a MAO/A inhibitor (Brofaromine) in
      patients with Alzheimer's disease. Participants were initially assessed at the
      clinic (baseline) and then randomly allocated to in-home or in-clinic assessments
      for the remainder of the trial. The baseline and second assessment (performed
      before initiation of the treatment) were used for the reliability analysis.
      Withdrawal rates were examined over the course of the 6-month trial. SETTING:
      Assessments took place at a geriatric clinic in an urban university teaching
      hospital and at residences of some of the patients. PARTICIPANTS: Forty-six
      Alzheimer's disease patients participated in the study, of which, 22 were
      randomized to in-home assessments and 24 to in-clinic assessments. MEASUREMENTS:
      Test-retest reliability was measured for all five instruments used in the study
      and was based on the first two assessments. Sample size requirements, based on
      within-group variance, were calculated. Withdrawal rates were obtained for the
      total duration of the trial. RESULTS: Test-retest reliability of the instruments,
      as determined by intraclass correlations, was good in both groups but favored in
      clinic for all but one instrument (range: 0.47-0.90 for in-home vs 0.57-0.92 for
      in-clinic). Sample size requirements based on reliability assessment data were
      found to be larger for some instruments when administered in-home. Only four in
      home patients withdrew before completion of the study, compared with eight in
      clinic patients. CONCLUSION: The results suggest the in-home assessments in
      cognitively impaired older adults may result in lower withdrawal rates but may
      necessitate larger sample sizes to offset larger test-retest variability.

PMID- 7560705
TI  - Limiting treatment in nursing homes: knowledge and attitudes of nursing home
      medical directors.
AB  - OBJECTIVE: To determine nursing home medical directors' knowledge about
      cardiopulmonary resuscitation outcome and their support of treatment limitation
      requests and policies. DESIGN: Mailed questionnaire, followed by telephone
      interview. PARTICIPANTS: Forty-six medical directors of 70 community nursing
      homes in Harris County, Texas. MEASUREMENTS: Medical directors were asked to
      estimate the CPR survival rate to discharge of all nursing home residents and
      that of two case scenarios. They were asked to indicate on a Likert scale their
      support for mandatory Do-Not-Resuscitate orders and for requests by nursing home
      patients to withhold other life support measures. RESULTS: Responses were
      received from 33 directors. Overall CPR survival rate of older nursing home
      residents after cardiac arrest was thought to be 10.7%. The average CPR survival
      rate for healthy older people with witnessed arrests was believed to be 13.8%.
      The perceived rate for unwitnessed arrests in terminal patients was 4.6%,
      significantly lower than estimates for healthy older people (P = .003) and
      estimates of the overall survival rate (P = .02). Medical directors were split
      regarding mandatory Do-Not-Resuscitate orders for patients in vegetative states,
      with terminal illness, with an unwitnessed arrest, or in those older than 90
      years of age. Mandatory use of Do-Not-Resuscitate orders for all nursing home
      residents was strongly opposed. Assuming a 2% survival rate did not significantly
      influence medical directors' opinions about mandatory DNR orders in these groups.
      Medical directors were more willing to support requests by stable nursing home
      residents to withhold resuscitation, mechanical ventilation, or hospitalization
      than requests to withhold antibiotics, intravenous fluids, or tube feedings (P <
      .005). The majority of medical directors were willing to withhold all such
      measures for terminal patients. CONCLUSIONS: Health care professionals who are
      responsible for educating patients about the efficacy of cardiopulmonary
      resuscitation in nursing homes overestimate its benefit and may benefit from
      further education about its outcome. Although mandatory Do-Not-Resuscitate orders
      were favored for terminal or vegetative patients, medical directors are not
      supportive of such orders across the board. Medical directors are more willing to
      honor requests for treatment limitation by terminal patients than others.

PMID- 7560706
TI  - The use of medicines with anticholinergic effects in older people: a population
      study in an urban area of Sweden.
AB  - OBJECTIVE: To investigate the use of medicines with anticholinergic properties
      among older people in an urban population in Sweden. DESIGN: A cross-sectional
      survey. SETTING: Ordinary homes, sheltered accommodations, nursing homes, and
      geriatric departments. PARTICIPANTS: All residents aged 75 and older in a
      district of Stockholm, Sweden. MEASUREMENTS: Structured interviews with older
      persons, their relatives and/or health care personnel; prescription forms;
      medical records. RESULTS: The overall use of medicines with anticholinergic
      effects was comparatively low. Doses of these medicines were also generally low.
      Concurrent use of several such medicines was uncommon. The most prevalent
      therapeutic/pharmacological group was neuroleptics. In contrast, antidepressants
      were used by few older people. The prevalence of medicines with anticholinergic
      effects was highest at institutions, where neuroleptics were frequent and use of
      low-potency neuroleptics was not uncommon. CONCLUSION: Our results indicate that
      the risk of anticholinergic side effects may be quite low in the present
      population as a whole. However, there may be grounds for revising the therapy in
      institutions, where the use of neuroleptics was shown to be high and low-potency
      neuroleptics, known to have a higher incidence of anticholinergic side effects,
      were not avoided.

PMID- 7560707
TI  - Falls among older people: relationship to medication use and orthostatic
      hypotension.
AB  - OBJECTIVE: To assess the risk of falls attributable to medication use and
      orthostatic hypotension. DESIGN: Prospective cohort study. SETTING: Two self
      care, apartment-style residential facilities in the Toronto area. PARTICIPANTS: A
      total of 100 consecutive older volunteers (mean age = 83, range 62-96) who were
      independent in activities of daily living and able to stand unaided.
      MEASUREMENTS: Prescription medications used by each subject were documented at
      baseline. Blood pressure measurements were performed supine, immediately after
      standing, and after 5 minutes. Subjects reported falls weekly, by postcard, for a
      period of 1 year; nonreporters were contacted by telephone. RESULTS: Fifty-nine
      percent of subjects fell at least once during the 1-year follow-up.
      Antidepressant use was associated with an increase in the risk of experiencing
      one or more falls (RR = 1.6, P = .02). The use of other drug classes examined,
      including diuretics and sedative-hypnotics, was not associated with an increased
      risk of falling. Orthostatic hypotension was not predictive of falls.
      Surprisingly, there was an increase in the diastolic blood pressure of fallers,
      after 5 minutes, that was not seen in the nonfallers (3.3 vs -0.2 mm Hg, P =
      .05). Possible explanations for this previously unreported observation are
      explored. CONCLUSION: Patients using antidepressants should be followed closely
      because the risk of falls is increased. Previously reported relationships between
      benzodiazepines and diuretics and falls are not supported by the present
      findings. Clinical detection of orthostatic hypotension is unlikely to be useful
      in predicting future risk of falling.

PMID- 7560708
TI  - Falls in community-dwelling older persons.

PMID- 7560709
TI  - The CARE Program: a nurse-managed collaborative outpatient program to improve
      function of frail older people. Collaborative Assessment and Rehabilitation for
      Elders.
AB  - BACKGROUND AND OBJECTIVES: Frail older adults are especially vulnerable in a
      health system that is fragmented and fails to focus on preservation or
      restoration of function. The School of Nursing at the University of Pennsylvania,
      together with the School of Medicine and the Hospital of the University of
      Pennsylvania, established the Collaborative Assessment and Rehabilitation for
      Elders (CARE) Program to meet the needs of this population. We used the British
      Day Hospital as a model because it provides a comprehensive approach to care and
      a bridge between acute, home-based, and institutional long-term care. We have
      designed our program to provide innovative, interdisciplinary care as well as to
      be reimbursable under current and future payment structures. This nurse-managed,
      collaborative practice seeks to maximize independent functioning, promote health,
      and enhance quality of life for chronically ill, frail older adults living in the
      community whose needs are left unmet by existing services. The program was
      certified as a Comprehensive Outpatient Rehabilitation Facility (CORF) in
      December 1993 to maximize reimbursement of services through Medicare and other
      third party payers. With a Gerontological Nurse Practitioner as care manager,
      clients receive an intensive, individualized, time-limited program of nursing,
      rehabilitation, mental health, social, and medical services in one setting
      several days each week. Additional geriatric services, such as primary care, are
      available in the same location when needed. SETTING: The program is housed in
      renovated space devoted to the care of older people. The academic and clinical
      offices of the University of Pennsylvania's nursing and medical gerontologic and
      geriatric faculty are in the same building. PARTICIPANTS: We have targeted those
      persons older than age 65 who have complex health problems and are living at
      home. Individuals must need multiple services, including at least one
      rehabilitation therapy, and they must be unsuitable-for inpatient rehabilitation.
      DESCRIPTION OF THE POPULATION: In its first 8 months of operation, the program
      received 97 referrals and admitted 53 clients. Clients were, on average, 78 years
      of age. Over three-fourths (77%) were women and 58% were black. The average stay
      in the program was 6 weeks. FIM scores, which improved a mean of 2.4 points, were
      found to lack sensitivity to the functional improvements achieved by clients.
      CONCLUSION: Under existing Medicare and third party reimbursement policies, it is
      feasible to establish a nurse-managed comprehensive outpatient rehabilitation
      program designed to meet the needs of frail older persons. Preliminary data
      support the beneficial effects of the program as well as the economic feasibility
      of this approach.

PMID- 7560710
TI  - An 82-year-old woman with weight loss and eosinophilia.

PMID- 7560711
TI  - Address to the American Geriatrics Society.

PMID- 7560712
TI  - Communicating with older patients: a challenge for researchers and clinicians.

PMID- 7560713
TI  - Falls, fallacies, and hypertension.

PMID- 7560714
TI  - From advocacy to tenacity: finding the limits.

PMID- 7560715
TI  - Access to hospice care.

PMID- 7560716
TI  - Access to hospice programs in end-stage dementia.

PMID- 7560717
TI  - The need for a "second witness" in diagnosing dementia.

PMID- 7560718
TI  - Pulmonary arterial hypertension in nonagenarians.

PMID- 7560719
TI  - Erythrocyte sedimentation rate in Alzheimer's dementia.

PMID- 7560721
TI  - Geriatric day hospitals.

PMID- 7560720
TI  - Confounding issues of bacteremic older adults.

PMID- 7560722
TI  - Adverse consequences of capsaicin exposure in health care workers.

PMID- 7560723
TI  - Enalapril and peripheral neuropathy.

PMID- 7560724
TI  - Recurrent and chronic leg ulcers secondary to furosemide-induced bullous
      pemphigoid.

PMID- 7560725
TI  - Research: where we go from here.

PMID- 7560726
TI  - Tear protein profiles vs. clinical characteristics of untreated and cyclosporine
      treated canine KCS.
AB  - BACKGROUND: Topically administered cyclosporine A (CsA) decreases ocular surface
      inflammation in canine keratoconjunctivitis sicca (KCS) and exerts lacrimomimetic
      effects. This study was performed to find correlations between clinical signs and
      tear protein levels in untreated and CsA-treated canine KCS. METHODS: Clinical
      profiles were scored in 16 KCS-affected dogs before and 6 weeks after commencing
      treatment with 0.2% topical CsA emulsion. Tear samples were also collected using
      polished micropipettes for specific protein assay by high-performance liquid
      chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Tear levels of serum proteins correlated with conjunctival clinical signs. Levels
      of lacrimal gland proteins in tears correlated most often with corneal clinical
      signs. CONCLUSIONS: The inflammatory features of KCS appear to link conjunctival
      signs to serum proteins in tears, while corneal signs are linked to lacrimal
      gland proteins.

PMID- 7560727
TI  - Animal models of emmetropization: matching axial length to the focal plane.
AB  - BACKGROUND: It has long been recognized that more people are emmetropic than
      would be expected from a random combination of the refractive and axial
      components of the eye. However, it has been difficult to determine whether this
      is the result of an active emmetropization mechanism. METHODS: This paper reviews
      some of the studies in animals that have been conducted during the past 20 years.
      Four basic paradigms have been used to determine whether the visual environment
      helps guide eyes to emmetropia: 1) observing the normal pattern of ocular
      development, 2) shifting the location of the focal plane with minus- (and plus-)
      power lenses, 3) removing focused images by visual form deprivation and, 4)
      restoring form vision after a period of visual deprivation. RESULTS: Data from
      many studies suggest that an active emmetropization mechanism guides the
      postnatal development of the eye, matching the axial length to the focal plane.
      In normal development, the axial length initially is generally short so that the
      photoreceptors are in front of the focal plane of the unaccommodated eye. The
      subsequent axial elongation eventually moves the photoreceptors to, but not past,
      the focal plane. When animals are raised with the focal plane shifted posteriorly
      with minus-power lenses, the eyes elongate to approximately match the displaced
      focal plane. When information about the location of the focal plane is removed by
      visual deprivation, the eyes elongate past the point of emmetropia and become
      myopic. When developing eyes that have become myopic from a brief period of form
      deprivation are re-exposed to patterned images, they can slow their axial
      elongation, gradually eliminating the myopia. Data from several species suggest
      that the axial length is regulated within the eye itself, involving direct,
      spatially local communication from the retina to the sclera. It also appears that
      the regulation of axial elongation involves active control of the scleral
      extracellular matrix. CONCLUSIONS: If humans have a similar mechanism, then
      successful emmetropization in children may involve two components. One is to
      inherit a fully functional emmetropization mechanism. Equally important is
      exposure to a "normal" visual environment. Deficiencies in either, or an
      interaction between a compromised mechanism and a non-optimal visual environment
      might also prevent emmetropization.

PMID- 7560728
TI  - The pupillary light reflex pathway of the primate.
AB  - BACKGROUND: Many studies of the pupillary light reflex pathway in mammals have
      indicated that the pretectum is important for this reflex. However, no single
      retinorecipient pretectal nucleus has been unequivocally identified as being
      involved in the light reflex pathway. In this study, anatomical studies in the
      rhesus monkey were carried out to identify the relevant retinorecipient pretectal
      nucleus and to better define the central pathway of this reflex. METHODS: An
      injection of Wheatgerm Agglutinin/Horseradish peroxidase, a neuroanatomical
      tracer, was placed under physiological guidance into the Edinger-Westphal
      nucleus. Intravitreal injection of the same tracer in another animal was used to
      define the pretectal retinal terminal fields. RESULTS: Following injection of
      tracer in the Edinger-Westphal nucleus, retrogradely labeled cells were found in
      only one retinorecipient nucleus, the pretectal olivary nucleus. Most labeled
      cells were located contralateral to the injection site. A few labeled cells were
      located ipsilaterally. Intravitreal injection of tracer resulted in anterograde
      labeling of all the retinorecipient pretectal nuclei, including the pretectal
      olivary nucleus. The retinal terminal field in the pretectal olivary nucleus
      coincided with the location of the cells that were retrogradely labeled by the
      injection of tracer into the Edinger-Westphal nucleus. CONCLUSIONS: These results
      demonstrate that there is a direct projection from the pretectum to the Edinger
      Westphal nucleus, that it arises from only one retinorecipient pretectal nucleus,
      the pretectal olivary nucleus, and that cells in the pretectal olivary nucleus
      almost all appear to project to the contralateral Edinger-Westphal nucleus.

PMID- 7560730
TI  - Human corneal oxygen demands at superior, central, and inferior sites.
AB  - BACKGROUND: Oxygen depletion of the superior and central cornea in response to
      standard conditions is of clinical interest because of pathological conditions,
      usually resulting from the hypoxia of contact lens wear, that affect these areas.
      A study was designed to determine if there are differences in oxygen depletion at
      these two sites. METHODS: Oxygen depletion times from a standard reservoir
      following corneal exposure to three different oxygenated environments (20.9%, 5%,
      and 0% oxygen) were assessed micropolarographically at central, superior, and
      inferior corneal surface positions on both corneas of six healthy young adult
      human subjects. RESULTS: Based on 48 measurements for each corneal position at
      each oxygen percentage (432 total measurements), the superior cornea 1.0 mm from
      the limbus was found to have longer oxygen depletion times (slower oxygen uptake
      rates) than the central or inferior corneal locations. The differences reduced to
      nearly zero during the course of the initial 1.5-day testing procedure, but were
      re-established months later when testing was resumed. CONCLUSIONS: There is a
      small reversible increase in superior corneal oxygen depletion time (a decrease
      of the oxygen uptake rate) due to the chronic hypoxia that results from the
      presence of an overlying superior eyelid or other physiological factors.

PMID- 7560729
TI  - Electrical stimulation of the pontine omnipause area inhibits eye blink.
AB  - BACKGROUND: Single-unit recordings of pontine omnipause neurons (OPN) in the
      monkey have shown that these neurons cease firing for saccades in all directions.
      OPNs are located in pontine nucleus raphe' interpositus and are known to inhibit
      a variety of target neurons, including saccadic burst neurons. Recently, a single
      unit investigation of these same OPNs revealed that they pause for blinks as well
      as saccades. Electrical microstimulation of the OPN area has been shown to
      inhibit saccadic eye movements in all directions. The present study is designed
      to determine if OPN area microstimulation inhibits blinks as well as saccades.
      METHODS: Two rhesus monkeys were trained to track visual targets for a reward.
      Eye and lid position were measured using the electromagnetic search coil
      technique. The pontine OPN area was located using single-unit recording and
      microstimulation techniques. OPN stimulation was delivered just before and during
      the presentation of air puffs to elicit blinks. RESULTS: OPN are microstimulation
      inhibited air puff-induced blinks as well as saccades. The threshold current for
      inhibiting blinks was generally slightly higher than for inhibiting saccades.
      CONCLUSIONS: Although OPN area stimulation inhibits blinks as well as saccades,
      the mechanisms for inhibiting these behaviors appears to be different. OPNs are
      known to inhibit saccadic burst neurons, but there is no evidence that these
      neurons inhibit orbicularis oculi motoneurons which burst for blinks. Moreover,
      the temporal pattern of OPN activity makes it unlikely that they directly
      suppress blinks. The OPN region appears to be important for eye retraction during
      blinks and may be associated with other pontine areas which control blinks.

PMID- 7560731
TI  - The reliability of interpretation of photoscreening results with the off PS-100
      in Headstart preschool children.
AB  - BACKGROUND: Photoscreening has emerged as one of the newest means of screening
      children to detect amblyogenic factors. In the preschool population, it is
      important to reliably screen children who are at risk for developing amblyopia.
      This research was undertaken to determine the reliability of the interpretation
      of photoscreening results in a Headstart preschool population. METHODS: Fifty
      four African-American children aged 3 to 5 years of age were examined using the
      MTI PS-100 photorefractor. Five health care professionals with no prior knowledge
      of photoscreening techniques were asked to perform independent, masked
      interpretations of a set of 54 Polaroid snapshots. Their interpretations followed
      a training session by a company consultant. RESULTS: The kappa coefficient for
      reliability of interpretation between observers was 0.55. This kappa value
      indicates that there was moderate agreement between the observers when
      identifying amblyogenic conditions in a child. CONCLUSIONS: Non-vision
      professionals using this device for the assessment of children will probably
      achieve only moderate levels of agreement on pass-fail decisions at first. Higher
      reliability reported previously by more experienced photoscreeners indicates that
      agreement could improve with advanced training, feedback regarding diagnostic
      findings, and experience. Methods to improve the technique, the device, or the
      training of the examiners are discussed.

PMID- 7560732
TI  - Corneal epithelial fluorescein staining.
AB  - BACKGROUND: There is some difference of opinion in the literature about the
      nature of fluorescein staining of the epithelial surface. Most authors support
      the view that fluorescein staining is due to drop out of cells and pooling of
      fluorescein in the footprint. Others believe that fluorescein fills intercellular
      spaces. Others suggest that cells themselves stain with fluorescein. METHODS:
      Rabbit corneas were stained with fluorescein and examined with the biomicroscope
      and later with a higher magnification epifluorescent microscope following
      excision. RESULTS: Fluorescein staining was shown to be due to staining of
      individual cells. No evidence was found to support the contention that
      fluorescein resides in areas of cell drop out, or that staining was due to
      filling of intercellular spaces. Micropunctate staining is shown to be due to
      staining of cells in an optimum manner, which is referred to as
      hyperfluorescence. CONCLUSIONS: The recognition that fluorescein stains cells,
      even in the case of epithelial abrasion, allows reinterpretation of many staining
      phenomena, including "salt and pepper" staining.

PMID- 7560733
TI  - The relationship between duration of superior oblique palsy and vertical fusional
      vergence, cyclodeviation, and diplopia.
AB  - BACKGROUND: The purpose of this study was to explore the relationship between the
      duration of superior oblique palsy (SOP) and relevant clinical findings. METHODS:
      We studied 39 patients with SOP and 14 patients with normal binocular vision
      (NBV). Vertical fusional vergences and cyclodeviations were measured through the
      habitual prescription. Each patient was asked if he or she currently experienced
      diplopia. To establish duration of SOP, those patients were asked and grouped
      according to whether they were diagnosed within the past 5 years, within the past
      6 to 15 years, or more than 15 years ago. RESULTS: The SOP patients were
      significantly different from the NBV patients on every measure except the infra
      recovery value. Among the SOP patients, the infra break value and the total break
      amplitude (infra plus supra) were the measures that were significantly different
      for the three SOP groups, increasing with the duration of the deviation. Since
      the infra break value was measured relative to any corrective prism in place, the
      total break amplitude proved to be the best distinguishing feature of duration of
      the SOP. There was no monotonic relation between the duration and the magnitude
      of the cyclodeviation. Likewise, there was no significant difference among the
      SOP groups in the frequency of reported diplopia even though there was a
      monotonic decrease in the percentage of diplopic patients with increasing
      duration of SOP. CONCLUSIONS: While an increased vergence amplitude and the
      presence of both diplopia and excyclodeviation distinguish patients with SOP from
      those with NBV, the total break amplitude is the only significant distinguishing
      feature of the duration of SOP.

PMID- 7560734
TI  - Topical anesthetic-induced methemoglobinemia and sulfhemoglobinemia in macaques:
      a comparison of benzocaine and lidocaine.
AB  - Benzocaine (BNZ) and lidocaine (LC) are commonly used topical (spray) anesthetics
      approved for use in humans. Benzocaine has structural similarities to
      methemoglobin (MHb)-forming drugs that are current candidates for cyanide
      prophylaxis, while LC has been reported to increase MHb in man. In this study, we
      compared MHb and sulfhemoglobin (SHb) production in three groups of Macaques
      (Chinese rhesus and Indian rhesus (Macaca mulatta) and pig-tailed macaques
      (Macaca nemestrina)) after exposure to BNZ and LC. Formation of SHb, unlike MHb,
      is not thought to be reversible and therefore is considered to be of greater
      toxic significance. Both MHb and SHb levels were measured periodically on a CO
      Oximeter. All rhesus macaques (n = 8) were administered an
      intratracheal/intranasal) dose of 56 mg (low dose) or 280 mg (high dose) of BNZ
      or 40 mg of LC in a randomized cross-over design (all animals received all three
      treatments). Pig-tailed macaques (n = 6) were given an intranasal dose of 56 mg
      of BNZ and 40 mg of LC. As no differences in the peak MHb or time to peak (mean
      +/- SD) were observed among the three macaque subspecies, the data were pooled.
      Lidocaine did not cause MHb or SHb formation above baseline in any monkey. In
      contrast, all monkeys (n = 14) had a significant elevation in peak MHb formation
      after 56 mg of BNZ, which ranged from 4.0% to 19.4% with an average of 8.6 +/-
      4.0% (mean +/- SD), with peak MHb levels reached at 30 min.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7560735
TI  - Evaluation of coal liquids derived from the EDS process in carcinogenesis
      screening tests.
AB  - Four process streams derived from the EDS not equal to direct coal liquefaction
      process were evaluated in two in vitro assays to screen for carcinogenic
      potential: the Salmonella/mammalian microsome mutagenicity assay and the Syrian
      hamster embryo morphologic transformation assay. Three high boiling liquids (two
      recycle solvents, nominal boiling range 200-425 degrees C; and a fuel oil blend,
      nominal boiling range 200-538 degrees C) were active in both assays. A
      hydrotreated naphtha sample (< 200 degrees C) was not active in either. The
      Salmonella data agreed qualitatively with results of dermal carcinogenesis
      studies; however, quantitative differences as measured by the estimation of
      mutagenic potency were apparent. The lack of quantitative agreement may have been
      related to the fact that the dermal carcinogenic activity of coal-derived
      synthetic fuels is predominantly associated with neutral polycyclic aromatic
      hydrocarbons, whereas activity in the Salmonella assay is strongly influenced by
      the presence of aromatic amines and nitroaromatic compounds. Two modifications of
      the Salmonella assay--detergent dispersion and hamster S9 activation--were
      examined. These techniques improved assay performance for some but not all of the
      coal liquids. The differences in response may have been related to compositional
      differences in the various liquids.

PMID- 7560736
TI  - Potency ranking of methemoglobin-forming agents.
AB  - This study represents the first systematic attempt to rank methemoglobin-forming
      agents. It is a quantitative potency ranking study utilizing linear regression
      analysis of dose-response data for comparative purposes. Six agents that are
      direct-acting and eight that require bioactivation were tested for their ability
      to induce methemoglobin formation in Dorset sheep erythrocytes under defined in
      vitro conditions. The agents were then ranked according to three complementary
      methods based on the slope of the linear regression, the calculated dose expected
      to induce a given amount of methemoglobin formation and the calculated percentage
      methemoglobin response induced by 1 mmol l-1 of the agent. The direct-acting
      agents, ranked from most to least potent inducers of methemoglobin formation,
      are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite >
      chlorate. The ranking from most to least potent inducers of the bioactivated
      agents are: alpha-naphthol > p-nitroaniline > m-nitroaniline, o-nitroaniline > p
      nitrotoluene = aniline > m-nitrotoluene = o-nitrotoluene. The ranking procedures
      are discussed and issues of interindividual variation and agent-specific
      sensitivities are addressed.

PMID- 7560737
TI  - Factors affecting the bioavailability of benzo[a]pyrene from oils in mouse skin:
      oil viscosity, grooming, activity and its prevention.
AB  - In the main study, tritium-labelled benzo[a]pyrene ([3H]BaP) was added to oils of
      a wide range of viscosity (from 13.5 to ca. 8000 cSt at 40 degrees C) and these
      were applied once to mouse skin under conditions where grooming was either
      allowed or prevented. The binding of [3H]BaP to epidermal protein and DNA was
      assessed. In addition, some studies were conducted to investigate the effect of
      prior oil exposure on binding levels and to compare binding levels following
      single and multiple application. It was found in the main study that the binding
      of [3H]BaP to both DNA and protein was increased as the viscosity of the oil
      vehicle decreased. Whereas only a twofold difference in DNA binding was found
      between the lowest and highest viscosity oil vehicle if grooming was allowed, a
      14-fold difference was seen if grooming was prevented. This was due to much
      higher binding levels with low viscosity oils when grooming was prevented.
      Protein binding showed similar results, although the difference between the
      grooming and non-grooming situations was slightly less. Whether grooming was
      prevented or not, both DNA and protein binding of [3H]BaP were found to be
      inversely proportional to the logarithm of viscosity of the oil vehicle, but when
      grooming was prevented, the slope for DNA binding was 10 times steeper than when
      it was permitted. Exposure of the skin to either high or low viscosity oils prior
      to the application of [3H]BaP in the same oil inhibited the binding to DNA but
      not to protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560739
TI  - Dermal absorption of polycyclic aromatic hydrocarbons in the blood-perfused pig
      ear.
AB  - Urinary 1-OH-pyrene, a metabolite of pyrene, is a sensitive biological marker for
      dermal absorption of pyrene in man. In order to determine whether this metabolite
      is a reliable biomarker of cutaneous absorption of other polycyclic aromatic
      hydrocarbons (PAHs), the blood-perfused pig ear model was used to compare the
      dermal absorption flux of pyrene with nine other PAHs after coal tar application.
      Cumulative absorption of PAHs into the perfusion blood, 200 min after application
      of an overdose of coal tar, ranged between 830 pmol cm-2 for phenanthrene to less
      than 4 pmol cm-2 for benzo[b]fluoroanthene, benzo[k]fluoranthene, benzo[a]pyrene,
      dibenzo[ah]anthracene and indeno[123-cd]pyrene. The results of this study show
      that when pyrene is used as a marker compound for PAH absorption through pig
      skin, the cumulative absorption of PAHs with a lower molecular weight will be
      underestimated: fluorene, tenfold; phenanthrene, 12-fold; anthracene and
      fluoranthene, ca. twofold. The percutaneous absorption of PAHs with a higher
      molecular weight than pyrene will be overestimated: e.g. benzo[a]pyrene,
      sevenfold; indeno [123-cd]pyrene, ca. 100-fold. It is likely that this conclusion
      is also valid for dermal PAH absorption in man.

PMID- 7560738
TI  - Ecological hazard assessment of aqueous soil extracts using FETAX. Frog Embryo
      Teratogenesis Assay--Xenopus.
AB  - Frog Embryo Teratogenesis Assay--Xenopus (FETAX) testing of a series of diverse
      hazardous waste-site soil samples was performed to evaluate the efficacy of FETAX
      as a rapid developmental toxicity screening tool for environmental hazard
      assessment. Soil samples were collected from six different hazardous waste sites,
      three from eastern and three from western Washington State. The type of waste
      site samples studied, based on the contaminants identified, included: heavy
      metals (2), polynuclear aromatic hydrocarbons, petroleum products (2) and
      organochlorine pesticides. Three to five samples from each site representing
      baseline and increasing levels of contamination were collected. Aqueous extracts
      of the soil samples were prepared and used for FETAX studies. Samples collected
      from the polynuclear aromatic hydrocarbon- and petroleum product-contaminated
      sites induced greater levels of embryolethal effects, although embryonic
      malformation was also observed. The metal-contaminated sites induced greater
      levels of embryonic malformation, but induced less embryolethality than the other
      samples evaluated. The organochlorine pesticide-contaminated site samples caused
      significant levels of embryonic deformities but failed to induce embryolethal
      effects. Results from these studies suggested that FETAX was sensitive enough to
      detect low levels of developmental toxicants but robust enough to be suitable for
      aqueous soil extract testing. FETAX may be used as a component of a battery of
      tests designed to assess potential ecological hazard.

PMID- 7560740
TI  - Monoisoamyl and mono-n-hexyl meso-2,3-dimercaptosuccinate in mobilizing 203Hg
      retention in relation to age of rats and route of administration.
AB  - Monoisoamyl (Mi-ADMS) and mono-n-hexyl (Mn-HDMS) monoesters of meso-2,3
      dimercaptosuccinic acid (DMSA) were given orally or parenterally for the
      mobilization of inorganic mercury in suckling and older rats. Chelators were
      administered at a dose of 2 x 0.5 mmol kg-1 on two consecutive days 2 weeks after
      a single 203Hg injection. Six days later, whole-body, kidney, liver and brain
      radioactivities were determined in gamma scintillation counters. Both Mi-ADMS and
      Mn-HDMS were found to be superior to DMSA in mobilizing mercury from body and
      organs. The results were similar after oral or parenteral treatment. The
      efficiency of both monoesters was even higher in younger than in older rats. This
      is the first report on the mobilization of mercury from the body of sucklings
      under conditions of late oral treatment.

PMID- 7560741
TI  - Histopathological changes in the respiratory tract of mice exposed to ten
      families of airborne chemicals.
AB  - The objective of this experimental work was to identify and compare the
      histopathological changes induced in the respiratory tract of Swiss mice exposed
      to repeated inhalation (4, 9 or 14 days) at typical concentrations of RD50, 0.3 x
      RD50 and 3 x RD50 of airborne chemicals. These substances were selected from ten
      chemical families: aldehydes, organic acids, alcohols, ketones, ethers, aromatic
      hydrocarbons, halogenated aromatic hydrocarbons, inorganic bases, amines and
      isocyanates. These experiments showed that the lesion intensity observed in the
      nasal passages varied with exposure duration and type of airborne chemical, but
      did not depend on the concentration of the substance. Results did not allow us to
      establish a relationship between the histopathological changes and the type of
      chemical family. No injuries were observed in trachea and lungs.

PMID- 7560742
TI  - Effect of s-triazine compounds on testosterone metabolism in the rat prostate.
AB  - The influence of s-triazine compounds (atrazine, prometryne and deethylatrazine)
      on testosterone conversion and 5 alpha-dihydrotestosterone-receptor complex
      formation was studied in vitro and in vivo in the rat prostate. A marked in vitro
      influence of atrazine and prometryne (from 0.465 to 1.392 mumol) and their
      mixtures (in total concentration, 0.928 mumol) on 5 alpha-dihydrotestosterone
      formation was detected. 5 alpha-Dihydrotestosterone-specific receptor complex
      formation was inhibited in vitro by ca. 0.5 mumol of atrazine or deethylatrazine
      and only in vivo by 6 mg of atrazine 100 g-1 body wt. daily during 7 days in the
      prostate cytosol. The inhibition of the enzymic activities responsible for
      testosterone conversion and steroid hormone-receptor complex formation was non
      competitive and reversible, and s-triazine compounds act as antiandrogens.

PMID- 7560743
TI  - Disturbances in rat smooth-muscle induced by a substance with fungicide action.
AB  - The fungicide substance QAS [N,N,N',N'-tetramethyl-N,N'-di(8,15-dichloropentadeca
      5,10- dien)ethylenediamine methylsulphate] has a biphasic effect on the
      spontaneous electrical and mechanical activity of smooth-muscle samples of rat
      corpus and guinea-pig taenia coli. During the first phase of QAS application
      membrane depolarization and increased spontaneous spike frequency were recorded.
      The tone of the preparations (resting tone) increased transiently. Calcium ion
      entry blockers did not affect the contractile effect of QAS, but K(+)-channel
      blockers and some modulators of the second messenger system abolished or
      decreased it. During the second phase depolarization increased progressively,
      spike frequency decreased and the increase in resting tone recorded during the
      first phase was eliminated. The results reveal that the long-lasting depolarizing
      effect of QAS (in concentrations used for plant protection) probably inactivates
      the entry of Ca2+ into the smooth-muscle cells and disturbs Ca2+ homeostasis.

PMID- 7560745
TI  - Serum biochemical and histopathological changes related to the hepatic function
      in pigs following atrazine treatment.
AB  - Biochemical and histopathological parameters of the hepatic function were used to
      quantify the hepatotoxic effects of atrazine in female pigs (gilts) undergoing
      intensive breeding. Female pigs (cross-bred Swedish and German landrace) received
      2 mg atrazine kg-1 body wt. in feed daily during 19 days of the oestrous cycle.
      The last treatment day corresponded to day -3 of the onset of the next expected
      oestrus. Blood samples were collected three times daily at 3-h intervals on the
      first four post-treatment days. Serum activities of gamma-glutamyltransferase
      (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and
      alkaline phosphatase (AP) were determined. Serum activity of GGT was
      significantly increased throughout the four post-treatment days. In comparison
      with the control values, a slight but not significant decrease was observed in
      the serum activities of ALT, AST and AP. Histopathological examination of the
      liver of exposed pigs showed mild centrolobular parenchymatous degeneration.
      Interstitial connective tissue proliferation resulted in narrow and irregular
      bile canaliculi.

PMID- 7560746
TI  - Perchlorates.

PMID- 7560747
TI  - Fronto-parietal control of electrodermal activity in the cat.
AB  - The aim of this work was to investigate the direct involvement of the fronto
      parietal cortex in the control of spinal autonomic centers eliciting
      electrodermal activity (EDA). This autonomic response, linked with the activity
      of sweat glands, was recorded as skin potential responses (SPRs) from forepaws in
      the cat. Animals were paralyzed by gallamine and SPRs were obtained under
      halothane anaesthesia. For each animal, a transection of the medulla sparing only
      pyramidal tracts was carried out. SPRs were elicited by direct electrical
      stimulation of pericruciate and posterior parietal cortical areas before and
      after such a transection. Results showed that in intact preparations, stimulation
      of the pericruciate cortex evoked SPRs at lower thresholds than the posterior
      parietal cortex. After the bulbar transection, only the stimulation of
      pericruciate areas still elicited SPRs at low intensities. Results are
      interpreted as indicating that fronto-parietal control of EDA is probably
      mediated by a double descending system: one involving corticoreticulospinal
      pathways and a direct corticospinal one. We hypothesized that the somatic motor
      cortex initiates descending programs to autonomic centers at bulbar and spinal
      levels, and that these centers are involved in autonomic adjustments to
      somatomotor movements.

PMID- 7560744
TI  - Effects of zearalenone and/or tamoxifen on swine and mink reproduction.
AB  - Tamoxifen (TAM), which binds to estrogen receptors and can act as an estrogen
      antagonist, was incorporated into the diets of swine and mink to determine if it
      would ameliorate the effects of the estrogenic mycotoxin zearalenone (ZEN). Sows
      and female mink were fed diets containing 2 ppm (swine) or 20 ppm (mink) ZEN
      and/or 10 ppm TAM from day 30 of gestation through weaning (swine) or from 2
      months prior to breeding through weaning (mink). The diets containing ZEN and/or
      TAM did not adversely affect reproduction in the sows. Although some
      hyperestrogenic effects on testes, uterine and ovarian weights were observed in
      the F1 piglets at 21 days of age, subsequent breeding performance was not
      affected. All the female mink exposed to ZEN mated, but only 25% whelped. No mink
      fed TAM (singly or in combination with ZEN) mated. Necropsy of these unmated
      females fed TAM revealed consistent severe pyometra. Histological examination of
      the reproductive tracts of the ZEN, TAM and ZEN + TAM-treated mink showed similar
      alterations, including ovarian follicular atrophy and degeneration, and mild to
      severe uterine atrophy, pyometra and endometritis. The results of these studies
      indicate that TAM was not effective in ameliorating the hyperestrogenic effects
      of ZEN in swine and mink, but rather it acted as an estrogen agonist.

PMID- 7560748
TI  - Endothelins and rat carotid body: autoradiographic and functional pharmacological
      studies.
AB  - The effects of ET-1 and ET-3 on ventilation and carotid chemosensory discharge
      have been studied in rats anaesthetised with pentotarbitone. Autoradiographic
      studies were also performed in vitro to investigate the binding of [125I]ET-1 to
      rat carotid body, nodose ganglion and brain stem. ET-1 caused a dose-related
      hyperventilation that was abolished by cutting both carotid sinus nerves.
      Recordings of chemosensory discharge from the carotid sinus nerve confirmed that
      ET-1 caused chemoexcitation. ET-3 had only slight effects. The hyperventilation
      evoked by ET-1 was antagonised by the ETA receptor antagonist FR139317, but
      responses to hypoxia (10% oxygen) and to cyanide were unaffected. [125I]ET-1
      bound to the carotid body, the nodose ganglion and to the brain stem,
      particularly in the region of the nucleus tractus solitarii. ET-1 binding in the
      carotid body was displaceable by FR139317, which is consistent with the
      functional evidence for ETA receptors in the carotid body. The effects of ET-1 on
      ventilation, coupled with the presence of ET binding sites in areas involved in
      respiratory and cardiovascular regulation, is consistent with a physiological
      role for ET in the control of respiration, but our evidence suggests that ET is
      not crucial for chemotransduction in acute hypoxia.

PMID- 7560749
TI  - Evidence for the presence of function of the inhibitory M2 receptors in the
      rabbit airways and lungs.
AB  - We investigated to determine whether or not the inhibitory M2-receptors function
      in the rabbit lung and heart. Rabbits were anesthetized, vagotomized, paralyzed
      and ventilated. Administration of gallamine, an M2-receptor antagonist, augmented
      an increase of PT produced by vagal stimulation with or without simultaneous
      administration of histamine and the increases were dose-dependent. Conversely,
      prior treatment with pilocarpine, an M2-receptor agonist, reduced these responses
      in a dose-dependent manner. The PT responses to histamine injection only were not
      significantly altered by administration of either gallamine or pilocarpine. The
      remaining bronchoconstrictor responses to the three stimuli in the presence of
      gallamine or pilocarpine were completely blocked by atropine. In another series
      of experiments, gallamine treatment enhanced bronchoconstriction evoked by vagal
      stimulation but reduced acetylcholine (ACh)-induced bronchoconstriction. These
      opposite responses were dose-dependent for gallamine. The results suggest that
      there are inhibitory M2-receptors in the parasympathetic nerves innervating the
      lungs in the rabbit. Furthermore, gallamine treatment that completely blocked
      bradycardia evoked by ACh administration reduced vagally-mediated bradycardia.
      This implies that gallamine appears to have an antagonistic action on muscarinic
      receptors in the rabbit heart.

PMID- 7560750
TI  - Modulation of muscle sympathetic activity during spontaneous and artificial
      ventilation and apnoea in humans.
AB  - Respiratory modulation of muscle sympathetic activity was compared in relaxed
      subjects breathing spontaneously and in anaesthetized and non-anaesthetized
      subjects ventilated artificially with intermittent positive pressure. Muscle
      sympathetic activity was recorded directly from the peroneal nerve using the
      microneurographic technique. Arterial pressure was monitored continuously either
      by finger-pulse photoplethysmography (Finapres) or intraarterially. Respiratory
      modulation of sympathetic activity, heart rate and arterial pressure was measured
      by averaging consecutive breaths to the ECG R-wave closest to the onset of
      inspiration. In relaxed subjects (n = 15) breathing quietly the averaged
      sympathetic activity was greatest during late expiration and the first half of
      inspiration and minimal after the peak of inspiration, after correcting for
      delays within the baroreflex loop. Systolic and diastolic pressures fell during
      inspiration. In anaesthetized or awake subjects ventilated artificially at normal
      tidal volumes the pattern of respiratory modulation of sympathetic activity was
      preserved but the changes in arterial pressure were reversed and respiratory
      sinus arrhythmia abolished. Ventilation with positive end-expiratory pressure (20
      cmH2O) increased the overall level of sympathetic activity and enhanced the
      breath-to-breath modulation. We conclude that, although baroreceptors provide
      potent modulation of muscle sympathetic activity in humans, the inspiratory
      inhibition of sympathetic activity does not depend on an increase in arterial
      pressure and hence an increase in baroreceptor input.

PMID- 7560751
TI  - Effects of static lung inflation on sympathetic activity in human muscle nerves
      at rest and during asphyxia.
AB  - Muscle sympathetic activity is inhibited during the second half of phasic lung
      inflation associated with normal (negative pressure) breathing or artificial
      ventilation with intermittent positive-pressure, and this inspiratory inhibition
      appears unrelated to the associated changes in arterial pressure. In this present
      study we tested the hypothesis that a static inflation of the lungs would cause a
      sustained inhibition of muscle sympathetic activity. Microneurographic techniques
      were used to record muscle sympathetic activity from the peroneal nerve, and
      arterial pressure was monitored continuously by finger-pulse photoplethysmography
      (Finapres). In nine subjects static lung inflation, brought about either actively
      or passively, caused a pronounced and sustained increase in sympathetic activity
      (not the predicted decrease) that could not be explained by changes in arterial
      pressure. When delivered at the end of a voluntary end-expiratory apnoea, static
      lung inflation caused an initial inhibition of the large chemoreceptor-induced
      sympathetic bursts and a subsequent excitation that was sustained for the
      duration of the lung inflation. These observations indicate that respiration can
      affect muscle sympathetic activity in humans in two opposing ways: inhibition
      during phasic increases in lung volume, and excitation during large static
      increases in lung volume. Neither phenomenon depends on changes in arterial
      pressure, and hence influences of carotid arterial and aortic (high-pressure)
      baroreceptors can be excluded. We suggest that the initial inhibition is evoked
      from lung or chest-wall receptors and the static exitation from unloading of
      cardiopulmonary (low pressure) baroreceptors.

PMID- 7560752
TI  - Localization of GABAA receptor immunoreactivity in NO synthase positive myenteric
      neurones.
AB  - GABAA receptors were localized within laminar preparations of the rat distal
      colon myenteric plexus using a monoclonal antibody (mAb 62-3G1) to the affinity
      purified GABAA receptor/benzodiazepine receptor/Cl- channel complex. The
      immunofluorescence procedure showed that approximately half of the myenteric
      ganglion cells displayed extensive GABAA receptor labelling of their soma. This
      population was further characterised by treating some GABAA-receptor-labelled
      laminar preparations for the histochemical demonstration of nitric oxide (NO)
      synthase-related NADPH-dependent diaphorase activity. A subpopulation of the
      GABAA-receptor-immunoreactive cells (35%) were also found to display intense NO
      synthase-related activity. These findings extend our understanding of the GABAA
      receptor-related innervation of the rat gut wall herein referred to as 'A
      GABAergic' and provides an anatomical basis for the pharmacologically-identified
      GABA-nitrergic pathway in the mammalian gut.

PMID- 7560753
TI  - Evidence for afferent fiber innervation of parasympathetic neurons of the guinea
      pig cardiac ganglion.
AB  - The present study was done to establish whether peptidergic afferent inputs can
      modulate parasympathetic neurons of the guinea-pig cardiac ganglion. Whole mount
      preparations from the guinea-pig heart were utilized to localize afferent
      terminals by immunohistochemistry and for intracellular recordings from
      individual neurons in situ. Action potentials could be elicited by both
      intracellular current injection and stimulation of interganglionic fiber bundles.
      Two types of neuron, phasic (95%) and tonic (5%) as defined by their firing
      properties, were observed. High frequency (5-10 Hz) interganglionic fiber
      stimulation produced a calcium-dependent, slow depolarization in many cells which
      was not blocked by 100 microM hexamethonium or 1 microM atropine. A prolonged
      depolarization was also produced by local application of capsaicin (1 mM), which
      releases substance P and CGRP from afferent nerve terminals. Microinjection of
      the mammalian tachykinins substance P, neurokinin A and neurokinin B (all at 100
      microM), also produced a slow depolarization. Application of specific agonists
      for the tachykinin receptor subtypes indicated that these neurons express both
      NK2 and NK3 receptors. Individual cells were filled with neurobiotin to examine
      their morphology and the preparations were counter-stained for SP-like
      immunoreactivity. The results demonstrated that SP-positive fibers are found in
      close apposition to both phasic and tonic neurons. From these results, we suggest
      that the parasympathetic neurons of the guinea-pig cardiac ganglion receive
      inputs from peptidergic, afferent fibers and that this input provides a pathway
      for potential local reflex control of cardiac function.

PMID- 7560754
TI  - Adenosine activates cardiac sympathetic afferent fibers and potentiates the
      excitation induced by coronary occlusion.
AB  - Adenosine is a possible mediator of cardiac pain during myocardial ischemia;
      however, little is known about the influence of adenosine on cardiac sympathetic
      afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized,
      decerebrated, curarized and artificially ventilated cats, we studied the impulse
      activity of 20 single afferent sympathetic fibers with a left ventricular
      receptive field in relation to epicardial applications of adenosine, coronary
      artery occlusions and arterial pressure rises. All fibers increased their impulse
      activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/-
      8%) rises in aortic pressure, thus exhibiting low-threshold receptor
      characteristics. In 10 cats, epicardial applications of three different doses of
      adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with
      dose-related responses. This response was abolished by aminophylline, a P1
      purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s
      occlusions of the coronary arterial vessel supplying the receptive fields of the
      fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively,
      after the end of excitation induced by adenosine (1 mg/ml) application. During
      the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to
      5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the
      second occlusion initiated 30 s after the end of adenosine-induced activation. In
      contrast, a significant potentiation of the response was observed (8.8 +/- 1.2
      vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the
      end of excitation by adenosine. This effect was no longer present during the last
      occlusion performed after 7 min. When the protocol was repeated substituting
      adenosine with saline (n = 5) or after i.v. administration of aminophylline (n =
      5), no potentiation was observed, even though the excitatory response to coronary
      occlusion was preserved. These data show that adenosine can activate cardiac
      sympathetic afferent fibers in a dose-related manner, and potentiate their
      responses to coronary occlusion, while leaving unaffected the responsiveness to a
      hemodynamic stimulus. The excitatory effects are likely to involve the P1
      purinergic receptors. The potentiation phenomenon might play a role in the
      genesis of an algogenic code.

PMID- 7560755
TI  - Distribution of neurotensin-immunoreactive neurons in the digestive tract of the
      chicken.
AB  - The origin of the neurotensin-containing nerve fibers in the digestive tract of
      the chicken has been investigated with the use of colchicine and
      immunohistochemistry. Neurotensin-immunoreactive nerve fibers were found in the
      smooth muscle layers from the esophagus to the duodenum. Their density of
      distribution was very high in the esophagus and crop (maximum mean value:
      1315/mm2 of sectional area in the lamina muscularis mucosae of the crop) and
      decreased progressively to the duodenum. Neurotensin-immunoreactive neuronal cell
      bodies were observed after colchicine treatment in the submucosal plexuses of the
      esophagus and crop and in the myenteric plexuses of the esophagus, crop,
      proventriculus and gizzard, and they extended varicose fibers. The number of
      neurotensin-immunoreactive cell bodies was high in the myenteric plexus of the
      gizzard (28.3 +/- 2.7/ganglion) but low in the plexuses of the esophagus, crop
      and proventriculus. Seven days after cutting the glossopharyngeal nerve and vagus
      nerve unilaterally, the number and extent of neurotensin-immunostained structures
      in the smooth muscle layers from the esophagus to the gizzard did not show any
      significant difference between operated and unoperated sides. These results
      indicate that in the chicken the great majority of neurotensin-immunoreactive
      enteric fibers originate in the intramural plexuses of the upper digestive wall
      and are mainly distributed to smooth muscle cells.

PMID- 7560756
TI  - Effect of lateral hypothalamus lesions on the water and salt intake, and sodium
      and urine excretion induced by activation of the median preoptic nucleus in
      conscious rats.
AB  - In this study we investigated the influence of electrolytic lesion of the lateral
      hypothalamus (LH) on the water and salt appetite, and the natriuretic, diuretic
      and cardiovascular effects induced by angiotensinergic, cholinergic and
      noradrenergic stimulation of the median preoptic nucleus (MnPO) in rats. Male
      Holtzman rats were implanted with a cannula into the MnPO. Other groups of sham-
      and LH-lesioned rats received a stainless steel cannula implanted into the MnPO.
      ANGII injection into the MnPO induced water and sodium intake, and natriuretic,
      diuretic, pressor and tachycardic responses. Carbachol induced water intake, and
      natriuretic, pressor and bradycardic responses, whereas noradrenaline increased
      urine, sodium excretion and blood pressure, and induced bradycardia. In rats
      submitted to LH-lesion only, water and sodium intake was reduced compared with
      sham rats. LH lesion also reduced the sodium ingestion induced by ANGII (12 ng)
      into the MnPO. In LH-lesioned rats, the dipsogenic, diuretic and pressor
      responses induced by ANGII (12 ng), carbachol (2 nmol) and noradrenaline (20
      nmol) injection into the MnPO were reduced. The same occurred with sodium
      excretion when carbachol (2 nmol) and noradrenaline (20 nmol) were injected into
      the MnPO of LH-lesioned rats, whereas ANGII (12 ng) induced an increase in sodium
      excretion. These data show that electrolytic lesion of the LH reduces fluid and
      sodium intake, and pressor responses to angiotensinergic, cholinergic and
      noradrenergic activation of the MnPO. LH involvement with MnPO excitatory and
      inhibitory mechanisms related to water and sodium intake, sodium excretion and
      cardiovascular control is suggested.

PMID- 7560757
TI  - Sympathetic and afferent neurones projecting into forelimb and trunk nerves and
      the anatomical organization of the thoracic sympathetic outflow of the rat.
AB  - The anatomy of the cervicothoracic sympathetic nerves was studied in the rat.
      Details of the arrangements of white and grey rami communicantes and superior
      cervical, middle cervical and stellate ganglia are given. Dorsal root and
      sympathetic ganglion neurones projecting to skin and muscle of the forelimb and
      trunk were labelled retrogradely with horseradish peroxidase (HRP) in order to
      study their number, segmental distribution and location. HRP was applied to
      forelimb nerves supplying skeletal muscles (Ramus profundus of radial nerve, RP)
      or hairy skin (N. cutaneus brachii lateralis superior of axillary nerve, CB), to
      mixed nerves (median nerve, ME; ulnar nerve, UL; radial nerve, RA) and to
      segmental thoracic nerves supplying hairy skin of the back (dorsal cutaneous
      nerve, CD) and to mixed internal intercostal nerves (IC). All sensory and
      sympathetic neurones were located ipsilaterally. In the forelimb nerves sensory
      somata were commonly restricted to two or three adjacent dorsal root ganglia
      (usually C6-7 for CB; C7-8 for ME; C7-Th1 for RA and RP; C8-Th1 for UL). Nearly
      all of the sympathetic somata were located in the middle cervical and stellate
      ganglia (fusion of C6-Th3). Some 0-0.4% lay in Th4 and Th5, none in the superior
      cervical ganglia. In the trunk nerves sensory somata were strictly segmentally
      organized. Sympathetic somata were distributed more widely over 4-5 segments with
      50-55% in the segmental ganglion and up to 41% in the next caudal segment. From
      the data, it is estimated that 400 sympathetic (28%) and 1050 afferent neurones
      project into CB, 1660 (29%) and 4050 into RA, 540 (42%) and 760 into RP, 1010
      (22%) and 3670 into ME, 880 (22%) and 3040 into UL, 350 (25%) and 1040 into IC
      and 500 (27%) and 1370 into CD.

PMID- 7560758
TI  - Arteriovenous anastomoses and the thermoregulatory shift between cutaneous
      vasoconstrictor and vasodilator reflexes.
AB  - The reflex changes in skin blood flow which occur in response to various non
      thermal stimuli (e.g., deep inspiratory gasps, arousing or painful stimuli,
      emotional stress) are profoundly influenced by the thermoregulatory state. The
      aim of the present study was to evaluate the involvement of arteriovenous
      anastomoses in the thermoregulatory modulation of skin vasomotor reflexes
      elicited by painful intraneural electrical stimulation and emotional stress
      (forced arithmetics), respectively. Vasomotor responses were recorded with laser
      Doppler flowmeters (LDF) placed on glabrous skin containing arteriovenous
      anastomoses (3rd finger and thenar eminence) and hairy skin which lack them
      (dorsal side of the first metacarpal bone). In some experiments, a laser Doppler
      flowmeter emitting laser light of two different wavelengths (infrared and green
      light) into the same skin site was used to record skin perfusion at different
      depths of glabrous skin on the thenar eminence. 40 subjects were investigated,
      both in the cold state (finger skin temperatures below 25 degrees C) and after
      subsequent warming (finger skin temperatures above 30 degrees C).
      Thermoregulatory modulation of electrical stimulation- or stress-induced
      vasomotor reflexes occurred both in glabrous and hairy skin, but hairy skin
      differed from glabrous skin by showing no significant vasoconstrictions. Relative
      perfusion changes were most marked in laser Doppler flowmeter recordings using
      the deeper penetrating infrared light. The results suggest that arteriovenous
      anastomoses are major contributors to the vasoconstrictor component of vasomotor
      reflexes in glabrous skin of warm subjects. The reflex increase in perfusion, on
      the other hand, which occurs in both glabrous and hairy skin of cold subjects may
      be mediated by resistance vessels.

PMID- 7560760
TI  - A scintigraphical qualitative analysis of peripheral vascular sympathetic
      function with meta-[123I]iodobenzylguanidine in neurological patients with
      autonomic failure.
AB  - In order to assess qualitatively the sympathetic functions of the peripheral
      vessels, we performed a scintigraphical study of the entire body with meta
      [123I]iodobenzylguanidine (MIBG) in 13 patients with autonomic failure and 11
      healthy subjects as control. The patients comprised seven with multiple system
      atrophy (MSA), two with pure autonomic failure (PAF), three with Parkinson's
      disease with autonomic failure (PD with AF) and one with familial amyloid
      polyneuropathy (FAP). No clinical evidence of vascular disease was noted in any
      of the patients and the control subjects. We investigated their autonomic
      functions using the head up tilt test as well as norepinephrine and isoproterenol
      infusion tests. We found that: (i) All of the control subjects showed
      satisfactory MIBG uptake; (ii) all of the patients with PAF and FAP, most of whom
      had postganglionic sympathetic lesions, showed supersensitivity and low MIBG
      uptake; (iii) almost all the patients with MSA, who were considered to have
      mainly preganglionic sympathetic lesions, showed supersensitivity and diminished
      MIBG uptake, although the patients with olivopontocerebellar atrophy showed
      supersensitivity but not diminished MIBG uptake. In conclusion, these results
      suggest that peripheral vascular scintigraphy using MIBG is useful in detecting
      peripheral adrenergic dysfunction.

PMID- 7560759
TI  - A causal relationship between fluctuations in thermoregulatory skin perfusion and
      respiratory movements in man.
AB  - The relationship between regular respiration with normal tidal volume and
      spontaneous fluctuations in blood flow through skin arteriovenous anastomoses
      (AVAs) was investigated. Laser Doppler measurements from skin areas known to
      contain arteriovenous anastomoses, ultrasound Doppler measurements from the
      radial artery and respiratory movements were recorded simultaneously in 7 supine
      human subjects in a thermoneutral environment. The phase relationship between
      respiration and the onset of sudden arteriovenous anastomoses vasoconstrictions
      was calculated in each subject. A few seconds before a vasoconstriction, there
      was a clear tendency towards synchrony in the respiration recordings, indicating
      that some respiration-phase-dependent event precedes the vasoconstrictions. Since
      arteriovenous anastomoses constrictions are accompanied by specific changes in
      heart rate and blood pressure, our findings link respiration to low-frequency
      heart rate and blood-pressure variability in humans.

PMID- 7560761
TI  - Effect of chemical sympathectomy on serum levels of thyroid hormones and the
      biochemical profile of domestic pigeons.
AB  - Recent studies have stressed the importance of the cholinergic system on avian
      metabolism. However, the role of the sympathetic nervous system (SNS) remains
      unclear. The present study was, therefore, aimed to probe the mechanisms for
      modulation of avian metabolism by the sympathetic nervous system after inhibition
      of the adrenergic responses. Activities of serum thyroid hormones (tri
      iodothyronine, T3, and thyroxine, T4), body weight, hepatic weight, as well as
      total lipid and water content in the liver and body temperature were some of the
      parameters examined after chemical sympathectomy with 6-hydroxydopamine (6-OHDA)
      and reserpine treatment in 24-h starved pigeons. In addition, glucose was
      administered to the pigeons to identify the regulatory role played by glucose
      after disruption of the SNS. A reduction in body weight of the pigeons and an
      enhancement in the lipogenic machinery along with a corresponding increase in
      water content were some of the obvious effects in 6-OHDA+reserpine treated, as
      well as glucose-loaded sympathectomized birds. The cloacal temperature (Tc) and
      both the thyroid hormones showed a drastic decrease while the T3/T4 ratio was
      augmented as a result of sympathectomy. However, serum T3 and T4 levels were
      restored to control values when glucose load was given, indicating that glucose
      might be reversing some of the detrimental effects of 6-OHDA treatment by
      activating intrinsic autoregulatory mechanisms of thyroid gland, thereby reviving
      the levels of thyroid hormones. Thus, the influence of SNS appears to be crucial
      in the maintenance of serum thyroid hormones and body temperature, as well as
      metabolic activities of hepatic cells.

PMID- 7560763
TI  - Developing a research strategy for child accident prevention via a cross-cultural
      picture card game.
AB  - This article discusses the research strategy applied during development of an
      educational picture card game for child accident prevention in South Africa.
      Preliminary results indicate that the strategy is appropriate and that the game
      may produce changes in children's knowledge and attitudes on this topic. It could
      be a valuable learning resource for promoting child health across different
      cultures.

PMID- 7560762
TI  - Chronic transection of post-ganglionic parasympathetic and nasociliary nerves
      does not affect local cerebral blood flow in the rat.
AB  - The role of post-ganglionic parasympathetic nerve fibers from the sphenopalatine
      ganglion and nasociliary nerve fibers from the trigeminal ganglion in the
      regulation of basal cerebral blood flow (CBF) was examined using rats, which had
      been divided into three groups; a sham group, a denervation group and a
      denervation+NG-monomethyl-L-arginine (L-NMMA) group. In the denervation and
      denervation+L-NMMA groups, unilateral chronic transection of the above nerve
      fibers had been performed at the ethmoidal foramen (EF) for 2 weeks. In the sham
      group, the above nerve fibers were only exposed at EF and not severed 2 weeks
      before the CBF measurement. Local CBF was measured by the [14C]iodoantipyrine
      autoradiographic method after intravenous administration of saline in the sham
      and denervation groups or L-NMMA (30 mg/kg) in the denervation+L-NMMA group. No
      significant difference in CBF was noted on each side in any of the regions
      between the sham and denervation groups. L-NMMA induced a significant reduction
      in local CBF on either side in each brain region. Neither the animals which were
      administered saline nor those with L-NMMA showed any side-to-side differences in
      local CBF in any of the brain regions examined. These findings suggest that the
      perivascular nerve fibers running through the EF, which are known to contain
      substantial nitric oxide synthase (NOS), may not play a pivotal role in the
      regulation of basal CBF. The reduction in CBF induced by the acute administration
      of L-NMMA was not affected by the chronic denervation of the above NOS-containing
      perivascular nerves.

PMID- 7560764
TI  - Customer satisfaction: the case for measurement.
AB  - The measurement of customer satisfaction is a process that is not commonly
      undertaken by medical illustration departments. The fact that many departments
      are now run on a zero-budgeted basis and rely totally on their 'customers' for
      their income has brought into sharper focus the need to ensure customer
      satisfaction with the services offered. This article discusses the background to
      customer satisfaction measurement and some of the techniques used.

PMID- 7560765
TI  - Intraoral and intranasal photography using a retinal fundus camera.
AB  - Like other subspecialities in biomedical imaging, clinical ophthalmic photography
      requires specialized instrumentation to produce informative photographs.
      Photographic slit-lamps, external ocular cameras, and retinal fundus cameras each
      have optical and illumination components that are designed to yield optimal
      results within narrow subject contexts. A variety of ophthalmic pathologies are
      associated with lesions in other parts of the body. One disease, cicatricial
      pemphigoid, causes changes in the mucosal tissue of the nasal and oral passages
      in addition to conjunctival findings. Lacking endoscopic instrumentation, we
      capitalized on the design parameters of a retinal fundus camera to produce
      photographs of these remote lesions.

PMID- 7560766
TI  - A method for duplicating bones as anatomical models.
AB  - Bones are a vital educational material in anatomy classes. However, it is not
      always easy to provide bones in sufficient quantity for a full class. In this
      article an easy method is presented for duplicating bones by using thermoplastic
      impression material and polymer cast material which can be used in anatomy
      laboratories with minimum cost. The method may be used to duplicate any bones,
      including rare anthropological bones or models made from materials like plaster
      or clay. Duplication of a mandible is described as an example.

PMID- 7560767
TI  - Educational technology transfer in newly independent states: developing a medical
      multimedia laboratory in Lithuania.
AB  - This paper discusses the development of an interactive multimedia computer
      laboratory within the Vilnius University Medical Faculty involving transfer of
      hardware and courseware developed in the USA. The contexts in which the
      laboratory was developed are described and factors helping and hindering
      successful technology transfer are identified. The future of the laboratory and
      its potential role in international distance education and information access are
      discussed. While this paper does not focus on international distance education in
      the traditional sense of offering courses or training from one or more source
      institutions to individuals off-site, it has implications for providing education
      internationally, especially in the Baltic and other newly independent states of
      the former USSR.

PMID- 7560768
TI  - [Indications of penetrating keratoplasty from a histopathological study of 1129
      corneal buttons (from 1982 to 1991)].
AB  - PURPOSE: To analyze the indications or the penetrating keratoplasties which were
      conducted in the Bordeaux University Hospital over the 1982-1991 period and to
      compare these findings with those of previously published studies. METHODS: The
      histopathological study of 1129 corneal buttons was analyzed according to
      conventional methods in the Histopathology Department Pellegrin Hospital.
      RESULTS: The main indications for penetrating keratoplasty were (in decreasing
      order of frequency): pseudophakic or aphakic corneal oedema (28.7%), keratoconus
      (12.1%), regrafts (11.1%), and corneal scars (10.7%). Less frequent indications
      for penetrating keratoplasty included Fuchs' endothelial dystrophy (7.8%);
      corneal trauma (7.3%) and herpes (7.2%). Ophthalmological conditions requiring
      penetrating keratoplasty fall into six groups of unequal size: 1) corneal oedema
      (28.7%); 2) keratitis (26%); 3) dystrophies (23.2%); 4) graft failures (11.1%);
      5) trauma and chemical burns (8%) and 6) miscellaneous (2.9%). CONCLUSION: The
      authors emphasize the importance of studying histologically the corneal buttons
      after penetrating keratoplasty. Corneal oedema after cataract surgery is shown,
      based on the data presented, to be the main indication for penetrating
      keratoplasty.

PMID- 7560769
TI  - [Contrast sensitivity in navigating seamen].
AB  - Visual acuity measurement is the ophthalmological test used for determining the
      majority of professional aptitude thresholds. In the case of ship pilotage
      however, the necessity to detect physical information of size and variable
      contrast can only be partly assessed by this parameter. AIMS OF THE STUDY: A test
      considered to be more ergonomic for the visual capacity evaluation of seamen, and
      for the early diagnosis of ocular abnormalities, was evaluated. METHOD: At the
      time of their statutory aptitude visit, 159 professional seamen underwent a test
      for morphoscopic sense at variable contrast and luminance, gradual. RESULTS:
      Twenty-seven ametropias of -0.75 to +3.00 diopters, 2 hypertensive retinopathies
      and 2 optical neuropathies were detected. Despite their low visual acuity, the
      myopic subjects were able to preserve normal visual efficiency in low contrast,
      without correction. Inversely, in spite of the correction, a deficiency was noted
      at medium and low contrasts, with a special increase at low luminance. The 7
      patients operated on for radial keratotomy, although their visual acuity reached
      10/10, presented a morphoscopic discrimination deficiency at low and medium
      contrasts. CONCLUSION: The test used in this study is designed for morphoscopic
      discrimination testing in which contrast and luminance are variable. This
      determination of luminance contrast sensibility seems to be an informative,
      sensitive and reliable means of detecting uncorrected ametropia and diverse
      organic pathologies at their inset.

PMID- 7560770
TI  - [Redox fluorometry study of corneal flavoproteins following hypoxia. Preliminary
      results].
AB  - PURPOSE: The cornea is frequently associated to hypoxia, whether during residence
      in the heights or more often when wearing contact lenses. To evaluate the corneal
      modifications induced by hypoxia at an infraclinical stage, we have used redox
      fluorometry that enables to study in vivo the metabolic response of the cells
      while measuring the fluorescence of the flavoproteins (FAD) of the corneal cells.
      METHODS: The variations of the corneal fluorescence were studied in 12 healthy
      subjects, before and after a topically-induced 5-minute corneal hypoxia,
      submitting 2 eyes to a prehumidified flow of nitrogen 100%. The results were
      compared to those found in the same subjects after exposure under the same
      conditions to an ambiant air flow (N2 = 69%; O2 = 21%). The measurements of the
      corneal fluorescence were carried out with the fluorophotometre Flurotron Master
      FM2. RESULTS: The authors did not find any statistically significant difference
      in the corneal fluorescence between the right and the left eyes of these 12
      subjects, whether under normal conditions, under hypoxia, or under air flow
      (wilcoxon T-test, Friedman test). CONCLUSION: As there are no significant
      results, these authors suggest that the chosen exposure time, although sufficient
      in vitro to induce a modification of the fluorecence of the cellular
      flavoproteins, may be too "short" in vivo. The use of complementary filters with
      the FM2 system would yield more information. The study of these results led the
      authors to broaden their search whether by looking for conditions for general
      hypoxia (hypobarric box) or by increasing local hypoxia (contact lenses).

PMID- 7560771
TI  - [Comparative prospective study of effects of Biovisc and Healonid on endothelial
      cell loss and intraocular pressure in cataract surgery].
AB  - PURPOSE: The goal of this trial was to evaluate the efficacy (protective action
      on corneal endothelium and ability to facilitate the procedure) as well as safety
      (effect on intraocular pressure and inflammation) of Biovisc (new viscoelastic
      agent made of 1% sodium hyaluronate produced by bacterial fermentation) versus
      Healonid) postcataract surgery (manual or phacoemulsification). METHODS: 106
      patients, 45 males and 61 females (31-94 years) were included in this prospective
      randomized multicentre trial and followed up for three months. Specular
      microscopy and intraocular pressure (IOP) measurement were the main evaluation
      criteria. RESULTS: At D 90, no significant difference was observed between the
      two viscoelastic agents on the mean endothelial cell loss (group Viovis: -8.6%;
      group Healonid: -6%) as well as on IOP (early peaks were transitory and
      resolutive). CONCLUSION: Biovisc and Healonid were similar in terms of efficacy
      and tolerance.

PMID- 7560772
TI  - [Use of liquid perfluorocarbons in vitrectomy for difficult cases of
      proliferative diabetic retinopathy].
AB  - PURPOSE: Thanks to their physical properties, could perfluorocarbon liquids
      (PFCL) be useful during vitrectomy for severe cases of proliferative diabetic
      vitreo-retinopathy (PDVR)? METHODS: Among 120 vitrectomies for PDVR performed in
      a period of time from August 1992 to July 1993, we reviewed 24 cases with a
      minimal follow-up of six months for which we have used PFCL as intraoperative
      tool. Among these eyes, three (12%) were preoperatively attached, seven (29%)
      presented with a tractional retinal detachment sparing the macular area and 14
      (59%) with a retinal detachment involving the macula. The indication for PFCL
      injection was either to flatten the retina in case of iatrogenic tear or
      retinotomy (15/24 eyes) or to stop a bleeding coming from the optic disc (9/24).
      The aim was to allow a good laser endophotocoagulation in all the cases and to
      inject an intraocular tamponade on a reattached retina if needed. As final
      tamponade, silicone oil was used in 10 eyes, gas in nine eyes and none in five
      eyes. RESULTS: At the end of the study, 20 (83%) eyes had a totally reattached
      retina and four (17%) a detached retina. The postoperative compared to the
      preoperative visual acuity was improved in 13 eyes (54%), unchanged in seven eyes
      (30%) and decreased in four eyes (16%). In one case (4%), some droplets of PFCL
      were noticed in the vitreous cavity, under the silicone oil bubble, with a good
      clinical tolerance. No specific complication of PFCL injection could be found in
      the 23 other eyes. CONCLUSION: In some selected cases of severe PDVR, the use of
      PFCL may help to flatten the retina, to stop bleeding from the optic disc and to
      perform a good endolaser photocoagulation. This allows to achieve good anatomical
      and visual results with few specific complications.

PMID- 7560774
TI  - [Analysis of the efficacy of the large mono-canalicular intubation stent in the
      treatment of lacrimation caused by congenital obstruction of the lacrimal ducts
      in infants].
AB  - BACKGROUND: Bicanaliculo-nasal intubation (BCNI) is considered as the method of
      choice in the treatment of naso-lacrimal duct obstruction (NLDO) in children.
      Side effects of BCNI are possible and monocanaliculo-nasal intubation (MCNI)
      provides the same results with fewer complications. Nevertheless, most of the
      short duration monocanaliculonasal stent complications concern the migration of
      the silicone stent in the canaliculus. We thought that this fact may be linked
      with the shape of the head of the monocanaliculonasal stent and decided to alter
      it. METHODS: Monocanaliculo-nasal intubation was performed in 52 cases, in 41
      children, using a modified silicone mono-canalicular stent (large collarette
      stent). RESULTS: The results were compared with a reference series of 52 cases
      treated with the classical silicone mono-canalicular stent intubation. The rate
      of success was comparable in both series, but fewer complications were observed
      with this new device. In particular, no migration of the silicone in the
      canaliculus occurred. CONCLUSION: The authors state that this modified mono
      canalicular stent decreases the lacrimo-nasal intubation morbidity without
      altering its effectiveness.

PMID- 7560773
TI  - [Outcome of Behcet disease in ophthalmologic practice in Morocco].
AB  - We treated 123 patients with Behcet's disease during a period of 10 years (1984
      1993). The ocular lesions include uveal lesions especially the posterior lesions
      and vascular retinal. Uveitis was total in 72% of cases. Periphlebitis occurred
      in 51% of cases, vein occlusion in 10% of cases, macular oedema in 16% and
      papillary oedema in 10%. Clinical course and prognosis were studied. The
      functional prognosis is poor as such lesions may lead to blindness, particularly
      due to papillary oedema maculopathy. The treatment used is based on
      immunosuppressive and corticoid steroid drugs.

PMID- 7560775
TI  - [Electric burns of the cornea. Anatomo-clinical study apropos of a case].
AB  - The authors report a 32-year-old Kurd patient who sustained bilateral corneal
      electrical burn by torture in 1982. A penetrating keratoplasty surgery was
      performed in 1992. The clinical and histopathological corneal diseases were
      described.

PMID- 7560776
TI  - [Post-traumatic fat embolism. Apropos of a case].
AB  - We describe the clinical, ophthalmoscopic, angiographic, and perimetric findings
      of fat embolism occurring in one patient with diaphysare femoral fracture. Fundus
      examination disclosed a bilateral cotton-wool spot retinopathy. Fluorescein
      angiography showed a masking effect of the cotton-wool spots. Visual field
      testing did not show scotoma in damaged areas of the retina.

PMID- 7560777
TI  - [Regressive bilateral retinoblastoma. Clinical and genetic study. Apropos of a
      case].
AB  - The authors report the observation of a 35-year-old patient, mother of 5 children
      4 of whom are carriers of bilateral retinoblastomas. Two of these children
      presented lesions suggestive of retinoma retinoblastoma association. The patient
      had peripheral retinal lesions evoking the diagnosis of regressive bilateral
      retinoblastoma. At present, the term retinoma or retinocytoma seems to be more
      adequate. The genetic study of this family was done with D esterase and DNA
      molecular biology.

PMID- 7560779
TI  - [Biopsy of an inflammatory pseudotumor of the orbit].

PMID- 7560778
TI  - [Paraneoplastic retinopathy associated with cutaneous melanoma. An update apropos
      of a case].
AB  - BACKGROUND: Ocular paraneoplastic syndromes are rare, and consist of optic
      neuropathy or retinopathy. Classically, these syndromes are related to carcinoma.
      Melanoma-associated retinopathy is extremely rare, and unrecognized. METHODS: A
      patient with metastatic cutaneous melanoma discovered and operated 18 months
      before. Visual complains consisted of xanthopsia and shimmering light vision,
      then hemeralopia, which dramatically worsened. Classical clinical examination,
      visual field and electroretinogram were performed. RESULTS: Visual acuity was
      20/25, and fundus examination was normal. The visual field showed a tubular
      aspect, with V4 isopter remained, like an advanced retinitis pigmentosa. The
      photopic electroretinogram was negative, and the scotopic one was flat.
      CONCLUSION: This recent hemeralopia with normal fundus and "negative"
      electroretinogram, ruled out congenital stationary night blindness diagnosis, and
      suggested the diagnosis of melanoma-associated retinopathy. This is a rare
      paraneoplastic syndrome since to date only 7 cases have been reported.
      Immunochemistry studies, that show antibodies directed against bipolar cells, are
      consistent with selective reduction of the electroretinogram b wave.

PMID- 7560780
TI  - [Who are candidates for Excimer laser surgery?].

PMID- 7560781
TI  - [Cyclic strabismus. Presentation of two new cases and critical review of the
      literature].
AB  - Description of cyclic strabismus has been restricted for a long time to circadian
      esotropia. In this mysterious phenomenon, the eyes are crossed every other day
      with no binocular vision, but remain perfectly normal during the straight days.
      The usual characteristics are those of a non-accommodative and non-paretic
      strabismus, with onset in early childhood. There is no response to conservative
      treatment, and the cycles become irregular with time until the deviation becomes
      constant, with an excellent functional result after surgery in every case.
      Recently, other papers comprising data irrelevant to the classic picture suggest
      that cyclic strabismus includes, in fact, several different entities. The only
      common point is the existence of ocular motility disorders that recur more or
      less regularly, and whose pathologic substrate is primarily heterogeneous,
      whether it is thought as a mere hypothesis or a likely mechanism. Two new cases
      of circadian esotropia are presented together with a review of the literature
      relating to the criteria of the syndrome.

PMID- 7560782
TI  - [Fluorophotometry of changes of hemato-ocular barriers in intermediate uveitis].
AB  - PURPOSE: Intermediate uveitis presents a characteristic clinical picture with
      inflammation in the vitreous and peripheral retina. From a physiological point of
      view, the disease is characterised by a rupture of blood-ocular barriers. To
      determine the sites involved, a vitreous fluorophotometry was performed in
      patients with intermediate uveitis and in a group of healthy patients. METHODS:
      Seventy-one patients with an intermediate uveitis were studied by vitreous
      fluorophotometry. Anterior chamber and posterior segment fluorophotometric
      findings were measured 5 and 60 minutes after injection of fluorescein. Results
      were compared to a group of healthy patients. RESULTS: Vitreous fluorophotometry
      demonstrated abnormal leakage of fluorescein in all vitreous sectors of the
      patients suffering from uveitis compared with the control group (p < 0.001). In
      the anterior chamber, leakage of fluorescein was not significantly different
      between the two groups (p > 0.05). CONCLUSION: Results obtained suggest that
      intermediate uveitis involves a generalized permeability disturbance of the
      posterior segment secondary to a diffuse vasculitis. However, in the anterior
      segment this disturbance is not found.

PMID- 7560783
TI  - [The eyelid of the competitive swimmer].
AB  - Two cases of pseudo-baggy eyelid localized to the medial part of the superior lid
      are described. This peculiar feature occurred in two teenagers girls who
      regularly wore hard plastic protective goggles during swimming competition.
      Wearing goggles is probably responsible for the development of this new, and to
      our knowledge, previously unreported syndrome. Clinicians should be aware of the
      typical signs and require about swimming practices in young women who present
      with an unusually baggy eyelid.

PMID- 7560784
TI  - [Uveitis with hypopyon in patients with acquired immunodeficiency syndrome,
      treated with Rifabutin].
AB  - BACKGROUND: Iridocyclitis has been identified as a dosage-dependent side effect
      in patients with the acquired immunodeficiency syndrome who are treated for
      Mycobacterium avium complex infections with systemic Rifabutin. We reviewed cases
      of acute hypopyon uveitis occurring in patients with AIDS to establish whether
      there was an association or not. METHODS: All patients were referred by an
      infection disease specialty service for complete ophthamological evaluation and
      ancillary laboratory. Six patients with AIDS, aged from 29 to 65 years, presented
      with acute unilateral hypopion. RESULTS: At the time of presentation, all six
      patients were receiving treatment for MAC infection with Rifabutin (dosage range,
      300-600 mg/d) and four received Fluconazol. Results of microbiological
      investigations were negative. Hypopyon developed in the second eye of two
      patients. Hypopion resolved rapidly with intensive antibiotherapy without
      corticosteroids. CONCLUSION: Concomitant use of Rifabutin and Fluconazol may
      precipitate hypopyon uveitis. The cause of the uveitis is less certain, but the
      possible role of a microbiological agent cannot be ruled out.

PMID- 7560785
TI  - [Measuring the level of tonic accomodation as a function of wavelength].
AB  - PURPOSE: Tonic accommodation contributes to the refractive state of the human eye
      in the absence of any visual stimulation. As the power of the eye, tonic
      accommodation level should be a function of wavelength and its variation should
      constitute a measure of longitudinal chromatic aberration of the eye. METHODS:
      The level of tonic accommodation was measured with a vernier optometer on a
      sample of 10 subjects (21-39 years). Five monochromatic filters of wavelengths
      450, 486, 550, 600, 656 nm have been used. RESULTS: Results show a tonic
      accommodation variation with wavelength. The sample mean of longitudinal
      chromatic aberration (left eye) resulting from the variation of tonic
      accommodation as a function of wavelength is 1.42 +/- 0.08 D between 450 and 656
      nm and 0.96 +/- 0.06 D between 486 and 656 nm. CONCLUSION: These results fit the
      predictions from theorical models and question previous results.

PMID- 7560786
TI  - [Treatment of refractory glaucoma by diode semiconductor laser
      cyclophotocoagulation].
AB  - PURPOSE: Ciliary photocoagulation was used to reduce pressure in eyes with
      refractory glaucoma or to suppress pain in blind painful eyes. The efficiency of
      transscleral cyclophotocoagulation (TSCPC) with a clinical diode laser system
      (Iris Medical Instrument, Oculight SLX) was evaluated. METHODS: This diode laser
      system (wavelengh: 810 nm) provides light energy to the eye through a specially
      designed quartz glass fiberoptic probe allowing precise location centered 1.2 mm
      behind the limbus, i.e. in front of the ciliary body. Thirty eight eyes in 38
      patients with refractory glaucoma underwent TSCPC with the diode laser. RESULTS:
      Three months after surgery, intra-ocular pressure was controlled at 20 mmHg or
      below in 70% of the patients. Patients who most failed with the TSCPC had higher
      initial IOP (neovascular and congenital glaucoma). Seventy five percent of the
      painful glaucoma were painless after the laser treatment. Only a few cases (10%)
      of transient secondary hypertony were observed. The inflammatory response (21%)
      was mild and transient. No case of scleral perforation, no case of posterior
      uveitis, cararact or hypotony were observed. CONCLUSION: The transscleral ciliary
      photocoagulation laser diode system is efficient to reduce intraocular pressure
      in refractory glaucoma. Complications are mild compared with other methods of
      cyclophotocoagulation. A long-term study is necessary to evaluate the results on
      IOP and the incidence of hypotony.

PMID- 7560787
TI  - [Results of treatment of undercorrections of radial keratotomy by Excimer laser].
AB  - Photorefractive keratectomy (PRK) was performed with Excimer Laser after
      undercorrected radial keratectomy in 21 eyes of 15 patients (maximum 8 incisions,
      3 mm optical zone). There was at least a 6-month interval between the two
      procedures. At the time of PRK, the mean age of the patients was 31 years and the
      mean spherical equivalent -2.3 D. Mean follow-up after PRK was 7.5 months; 10
      eyes were followed for more than one year. Quite satisfactory results were
      obtained since PRK was effective in 88% (eyes with uncorrected visual acuity of
      20/40 or better); predictability at +/- 1 D was 89%. Stable refractiveness was
      achieved at 3 months. The procedure is safe: there was no loss of best corrected
      visual acuity nor haze at one year. Other means of treating for undercorrection
      after refractive keratectomy were discussed in comparison with this technique.

PMID- 7560788
TI  - [Ocular burns caused by latex from manchineel trees].
AB  - OBJECTIVE OF THE STUDY: The objective of this study is to enter on an inventory
      and to appreciate the severity of the ocular burn caused by the latex of
      manchineel tree and to propose a therapeutic attitude. MATERIAL AND METHOD: We
      report on the results of a prospective study included 11 patients examined in the
      Department of Ophthalmology (Centre Hospitalier Universitaire de Fort-de-France)
      between November 1992 and November 1993. All of them presented with ocular burn
      due to a contact with the latex of the manchineel tree. RESULTS: The study
      included 11 patients, 8 adults and 3 children, the mean age was 22.9 years (range
      4-40). All of them had hyperhemia and conjunctival erosions of various intensity.
      Ten patients had corneal lesions: superficial punctate keratitis in 5 cases and
      corneal ulcers in 5 cases. Three cases of corneal ulcerations were associated
      with an inflammatory reaction of the anterior segment. Both eyes were affected in
      4 cases (37%), and only the right one in the other cases (63%). Seven patients
      had cutaneous lesions (63%), of whom 4 periocular burns of superficial second
      degree. Full recovery was obtained within 15 days for all the patients.
      CONCLUSION: Ocular lavage is the first treatment, as for all chemical burns.
      Local antibiotherapy is used systematically to prevent superinfection. With a
      proper treatment, a complete recovery with no sequelae is obtained.

PMID- 7560789
TI  - [Bilateral central retinal vein occlusion and circulating anticoagulant].
AB  - A case of central retinal vein occlusion with second development of the same type
      of retinal vein occlusion in the fellow eye, is reported. The patient was a 68
      year-old man with a history of thyroid gland disorder and a cardiac arrhythmia.
      He presented also with bilateral tilted disc. The first eye occlusion was
      initially nonischemic, but converted secondarily into an ischemic type and
      required laser panretinal photocoagulation. The biological assay found the
      presence of lupus anticoagulant antibodies and rheological findings (major plasma
      hyperviscosity, increased erythrocyte aggregation, high hematocrit and fibrinogen
      levels). The patient was given high doses of troxerutin, and aspirin. Central
      retinal vein occlusion occurred in the fellow eye one year later, a few weeks
      after the decrease of troxerutin doses. Hemodilution therapy was performed and
      visual acuity remained unchanged. Unusual risk factors for retinal vein occlusion
      are discussed. Lupus anticoagulant antibodies may sometimes lead to occlusive
      vascular phenomenon. Although these antibodies are not commonly found in retinal
      vascular occlusion, they may constitute a contributory factor. Tilted disc has
      often been involved in the pathogenesis of central retinal vein occlusion.
      Finally, abnormal rheological findings, major in this case, are found in more
      than half of the cases of retinal vein occlusion.

PMID- 7560790
TI  - [Colobomatous cyst of the orbit in congenital microphthalmos].
AB  - Colobomatous orbital cyst with microphthalmos is an anomaly of the orbital
      contents occurring during embryogenesis. In this study, we report the case of a 3
      year-old child referred with the initial diagnosis of voluminous orbital angioma.
      Radiological investigations and histological study of the ablated mass
      established the correct diagnosis of colobomatous cyst. Pathogeny, diagnostic and
      therapeutic problems are discussed.

PMID- 7560792
TI  - [Treatment of capsular complication in corneal incision].

PMID- 7560791
TI  - [Conjunctival myxoma. Apropos of an anatomo-clinical case].
AB  - In the ocular area, myxoma is a benign and uncommon tumor located essentially in
      the lids, more rarely in the conjunctiva. We report the case of a 31-year-old
      male suffering from the recent growth of an epibulbar painless tumefaction
      located in the temporal conjunctiva. This gelatinous mass was excised and has
      revealed a conjunctival myxoma. Surgical excision and histopathologic examination
      of such epibulabar lesions are necessary because they are few malignant tumors,
      like botryoid rhabdomyosarcoma or fibrosarcoma, which may have a similar clinical
      aspect.

PMID- 7560793
TI  - [Opinion of patients on the functioning of an ophthalmologic surgical outpatient
      center within a hospital. Analysis and consequences].
AB  - GOAL: The purpose of this analysis is to appreciate the patients perception of
      ambulatory cataract surgery performed in an out patient center localized inside a
      public hospital. MATERIAL AND METHODS: An anonymous postal questionnaire was
      designed to cover the aspects of ambulatory surgery which could influence the
      patients perception. 576 patients were included and the study collected 487
      answers to 12 questions. Authors give attention to the pros and cons detected
      during the study time. RESULTS: The key question shows that most patients
      recommend this procedure as the treatment of choice. The percentage increases
      with surgical experience of surgeons: the response rate to the questionnaire was
      both rapid and impressive. Final visual acuity did not influence significatively
      the overall perceptions of patients. CONCLUSION: Answers to the 12 questions
      point of importance of information, coordination and preparation. A high level of
      surgical and anesthetic formation is required to obtain an easy out patient
      ambulatory procedure.

PMID- 7560794
TI  - [Local anesthesia for cataract surgery in adults. Retrospective study of
      peribulbar, subconjunctival and topical anesthesia].
AB  - PURPOSE: A retrospective analysis of 4 methods of local anaesthesia for adult
      cataract surgery compares the efficiency of: peribulbar anaesthesia injection,
      subconjonctival anaesthesia injection, both of these techniques and eye topical
      anaesthesia. No sedation is used. All patients are classified in ASA I or ASA II
      grade of the anaesthesiologist classification. All the surgeries are performed in
      an out patient center. The anaesthetic solution combines equally bupivacaine
      0.5%, lidocaine 2% and hyaluronidase 250 UI. Phacoemulsification is performed
      through a scleral small incision. METHODS: 390 patients are separated in 4
      groups. Analgesia and Akinesia are evaluated in 3 levels: total, partial and
      absent. RESULTS: They show that a single peribulbar injection less of 8 ml is
      sufficient in 86.5% of cases. In case of a unique subconjonctival injection 2 ml
      are used with a rate of full success of 67.8%. When combining these 2 methods the
      surgery is easily possible in 97.9% of cases. A complementary subconjonctival
      injection is necessary in 4.9% of eyes receiving only the inferior peribulbar
      infiltration and in 13% of eyes anaesthezied by the single subconjonctival
      injection. 20.3% of eyes receiving only topical anaesthesia need a complementary
      subconjonctival injection during surgery. But the study covers the first series
      of patients operated with this new method, most of these cases are men. Results
      are better with experience, confidence and corneal incision. CONCLUSION: Local
      anaesthesia is a safe procedure offering very few local and general risks.
      General sedation or premedication is not necessary. The choice depends on the
      akinesia factor which is far more difficult to obtain with so few anaesthetic
      volumes than the analgesia.

PMID- 7560795
TI  - [Measurement of the visual acuity to networks with the Teller's cards: efficient
      detection of amblyopia in infants and young children?].
AB  - The reliability of measurement of visual acuity by Teller's card was studied in
      young children under 18 months (3 to 42.5 months) to detect amblyopia. Repeated
      tests with Teller's cards were performed in children (two exams at least) divided
      into several pathologies. Visual acuity changed over time (in 2000 exams).
      Results were compared with those given by drawing tests (Pigassou) at two years
      and a half. Middle amblyopia occurred in 44%, low amblyopia in 40% and high
      amblyopia in 16%, as the results by Teller's cards were considered as normal.
      These results were found in 54% among the 2000 Teller's studied. Teller's test
      was thus shown to be unreliable to detect middle or low amblyopia. Objective
      refraction is required.

PMID- 7560796
TI  - [Value of serodiagnosis of Lyme disease in the evaluation of uveitis].
AB  - PURPOSE: This study was designed to assess results of Lyme serology among all the
      specific tests routinely performed for exploring uveitis. METHODS: Sixty-seven
      patients examined for uveitis had a serological diagnosis of Lyme's disease with
      haemagglutination test and ELISA IgG test. This group included 34 patients with
      unclassified uveitis. Thirty-seven healty individuals served as control subjects.
      RESULTS: There was no statistical difference between the three groups in terms of
      positive serological diagnosis occurrence: control subjects (13.5%), patients
      with classified uveitis (12.1%) and patients with unclassified uveitis (11.8%).
      CONCLUSION: It appears to be more adequate to reserve this serological test for
      Lyme's disease for patients who have a suggestive history or additional symptoms.

PMID- 7560797
TI  - ["Melanoma 92". epidemiological study of uveal melanoma in France].
AB  - PURPOSE: The purposes of this study were to evaluate the incidence of uveal
      melanoma in France in 1992, to describe the characteristics of the tumors and
      their treatments. METHODS: This was a retrospective and multicentric study. First
      a questionnaire was sent to 4575 French ophthalmologists asking whether they had
      established a diagnosis of uveal melanoma during 1992, and if so, to describe the
      tumor and its management. Then the patients files were reviewed in the
      specialized treatment centers (Paris, Lyon, Nice, Strasbourg, Bordeaux, Clermont
      Ferrand). All the data were statistically analysed. RESULTS: 412 new cases of
      uveal melanomas were registered (incidence 0.7/100000) affecting 234 females and
      178 males. The cases ranged in age from 7 to 93 years (mean 61.5 years). There
      were 5 (1%) isolated tumors of the iris, 75 (18%) of the ciliary body, either
      isolated (10%) either associated to iris and/or to choroidal tumors and 332 (81%)
      choroidal melanomas. 201 (53%) tumors were posterior to the equator and 153 (40%)
      had a margin at less than 3 mm of the optic disc; 87 (21%) melanomas were
      detected in asymptomatic patients. In 29 (7%) other cases, the diagnosis was
      established after enlargement of the tumor. In all other eyes, symptoms were
      present. 17% of the melanomas were T1, 34% were T2, et 48% were T3. 353 (86%)
      melanomas were pigmented, 30 (7%) were achromic and 29 (7%) of the mixed color
      type. 156 (38%) tumors were associated with a retinal detachment. In 12 cases
      (3%), at presentation there was an extrascleral extension. 9 patients (2%) had
      metastases (7 to the liver, 1 to the lungs and 1 to the lungs and bones). The
      study of the patients residence and work did not show any environmental risk
      factor. The initial treatment was protontherapy in 251 patients (63%), plaque
      therapy in 91 (23%), enucleation in 40 (10%), and other methods in 18.
      CONCLUSION: This was the first epidemiologic study conducted in France on this
      subject. It describes the clinical features of the disease, its geographical
      display and its management in this country.

PMID- 7560798
TI  - [Uncommon ophthalmological involvement in chronic atrophic polychondritis].
AB  - OBJECTIVE: Report of two uncommon ocular manifestations of relapsing
      polychondritis (PR). METHODS: A 53 year-old woman presented with a uveal
      effusion. Diagnosis of PR was made 17 years later. A case of PR in a 41 year-old
      man is reported. The ocular manifestation was a pseudotumor of the lacrimal
      gland. CONCLUSION: The relapsing polychondritis must be known by the
      ophthalmologists. The ocular manifestations of this uncommon disease are
      significative and inflammatory.

PMID- 7560799
TI  - [SOPHOCLE (Ophthalmologic Simulator of Laser PHOtocoagulation): contribution to
      virtual reality].
AB  - PURPOSE: This study was undertaken to teach laser retinal photocoagulation in
      different disorders using a "virtual eye". Most ophthalmologists routinely use
      laser photocoagulator. Both indications and laser effects are well-known.
      However, in various diseases (diabetic retinopathy, age-related-macular
      degeneration, myopia...) complications rate increase or at least does not
      decrease. The main reasons are: - ignorance of risk factors, - misuse of the
      instrument. METHODS: We developed a new automated device stimulating a real laser
      photocoagulator. Only slit-lamp exists. The three-mirror lens, the fundus and the
      retinal photocoagulation impacts are "virtual". CONCLUSION: The aim of the
      simulator is to help practitioners to recognize various pathologies almost as in
      real conditions and to be familiar with different technics of photocoagulation.
      By using computer assisted learning, a constant evaluation determines the level
      and the progress of practitioners.

PMID- 7560800
TI  - [Floppy eyelid syndrome. Apropos of 4 cases and review of the literature].
AB  - Often unrecognized, Floppy eyelid syndrome is an impairment of the eyelid statics
      with marked conjunctival signs. Over-weight middle aged men are principally
      concerned. Excessive eyelid laxity in the Floppy eyelid syndrome is responsible
      for a night ectropion of the upper lid, creating the clinical manifestations. We
      report four cases of Floppy eyelid syndrome to illustrate our work and discuss
      the clinical and therapeutic aspects.

PMID- 7560801
TI  - [Langerhans cell granulomatosis of the orbit. Apropos of an anatomo-clinical
      case].
AB  - Langerhans' cell granulomatosis of the orbit was observed in a 7-year-old boy
      successfully treated by a simple biopsy. Recovery can be established one year
      after the biopsy on the basis of bone defect healing on the standard X-ray of the
      skull.

PMID- 7560802
TI  - [Macular complications of synthetic antimalarials. Apropos of a case].
AB  - The clinico-pathological findings in a 17-year-old girl with an "oeil de boeuf"
      maculopathy are reported together with the aetiological elements involved
      (hereditary or toxic maculopathy). The case was a second stage typical
      maculopathy due to antimalarial drugs. These patients were particularly
      susceptible, probably because of impaired renal function, since the total dose
      absorbed (140 g. chloroquine) was low. Ophthalmologic monitoring is required to
      prevent intoxication. Clinical examination, angiography and automatic perimetry
      and contrast sensitivity test are needed to detect the first effect of toxicity.

PMID- 7560803
TI  - [Surgery of idiopathic macular holes].

PMID- 7560804
TI  - [Treatment of endothelial cell loss and discreet corneal edema after anterior
      chamber implantation: a case].

PMID- 7560805
TI  - Serum soluble interleukin-2 receptors as an index of the biological activity of
      thyroid hormones in hyperthyroidism.
AB  - In order to examine whether serum soluble Interleukin-2 Receptors (sIL-2R) could
      be used as a marker of the biological effects of the thyroid hormones, we
      measured the sIL-2R, sex hormone binding globulin and beta-2 microglobulin levels
      in thirty-three hyperthyroid patients (14 with Graves' disease, 17 with Toxic
      Nodular Goiter and 2 with toxic adenoma) before and during treatment with
      antithyroid drugs. We found that serum sIL-2R concentrations of the patients, at
      diagnosis, were significantly higher compared with normal controls (2424 +/- 1447
      vs 459 +/- 184 U/ml). All hyperthyroid patients had sIL-2R levels > mean + 2SD of
      normal controls, with 28 of the 33 patients having sIL-2R concentrations higher
      than 1011 U/ml (mean + 3SD of normal controls). Only 15 patients had SHBG levels
      higher than 3SD above the mean for the normal controls and 28 had SHBG levels 2SD
      above the mean for the normal controls. Three of the 5 hyperthyroid patients with
      normal SHBG levels at presentation had abnormally high sIL-2R levels. In all
      patients sIL-2R levels decreased gradually during therapy down to normal levels
      when euthyroidism was achieved. A strong positive correlation was found between
      sIL-2R, SHBG and T3 and T4 concentrations. Serum B2-microglobulin (B2-m) levels
      were higher than the upper normal limit only in 9 patients, but a significant
      decrement was observed in all patients when euthyroidism was achieved. The above
      results indicate that serum sIL-2R levels could be a useful marker of the in vivo
      biological effects of the thyroid hormones on lymphocytes in hyperthyroid
      patients.

PMID- 7560807
TI  - Abnormal transduction of dopamine signal in human nonfunctioning pituitary
      adenomas.
AB  - It is well established that dopamine (DA) plays an important role in inhibiting
      anterior pituitary function. DA receptors present in the pituitary show the
      pharmacological and biochemical characteristics of the D2 receptor; in fact, they
      are coupled to the inhibition of both adenylyl cyclase (AC) activity and the
      reduction of cytosolic free Ca2+ levels ([Ca2+]i) suggesting the involvement of
      different G-proteins. While the DA receptors present in human PRL-omas display
      these characteristics, no information is available on the coupling mechanism(s)
      of DA receptors expressed in nonfunctioning pituitary adenomas (NF-PA). In the
      present study, the effect of DA on AC activity and [Ca2+]i was investigated in 8
      NFPAs surgically removed by the transphenoidal route. DA, at concentrations
      between 0.01 and 10 mumol/l, had no effect on cAMP formation in any tumor (from
      27.6 +/- 11.9 to 27.9 +/- 11.0 pmol/mg prot/min; NS). By contrast, DA was
      effective in reducing [Ca2+]i levels either in resting conditions or after TRH
      stimulation in 5 out of 8 tumors, suggesting that NFPA express DA receptors with
      a defective transduction mechanism. As in these tumors SRIH caused the expected
      inhibition of both AC activity (from 31.4 +/- 9.3 to 24.4 +/- 11.0 pmol/mg
      prot/min; p < 0.005) and [Ca2+]i levels, it is likely that the lack of DA action
      on AC activity may be due to functional/structural properties of DA receptors
      expressed in NFPA, instead of a defect at the level of Gi proteins. In
      conclusion, these data indicate that DA receptors expressed in NFPA show a
      defective transduction mechanism, leading to a partial inhibitory response.

PMID- 7560806
TI  - Heterogeneity of human luteinizing hormone in pituitary tumor homogenates and
      cell incubates.
AB  - Incubation media of pituitary cells and homogenates of pituitary tumors were
      studied by isoelectric focusing followed by radioimmunoassay. Almost all LH
      immunoreactive components detected had been observed in earlier studies on highly
      purified preparations. In one pituitary tumor homogenate, intact LH (LHi) was
      detected. The majority of LHi-components present in this tumor were relatively
      acidic (LH Type I) components. The corresponding beta-subunit population was in
      agreement with the one earlier observed for Type I LH. In all other tumor
      homogenates only alpha- and beta-subunits could be detected. In incubation media
      of pituitary cells from patients with no known endocrine disease nor a pituitary
      tumor highly acidic populations of alpha-subunits were detected. In only one of
      the incubation media significant amounts of LHi and free beta-subunits were
      observed. In an incubation medium of a TSH-producing pituitary tumor significant
      amounts of intact LH, free alpha- and beta-subunits were detected. The cell
      contents of this tumor contained components with lower pl-values than the medium.
      In general a good correlation is observed between the population of LH-components
      in material from individual identifiable pituitary glands and in highly purified
      preparations from large numbers of anonymous pituitary glands.

PMID- 7560808
TI  - Hepatic indices of thyroid status in rats treated with hexachlorobenzene.
AB  - The functional thyroid status of hexachlorobenzene (HCB)-treated rats was
      studied. HCB caused a depletion of serum thyroxine (T4), but did not change L
      3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the
      thyroid regulated mitochondrial enzyme L-glycerolphosphate dehydrogenase (LGPD)
      and cytosolic enzymes, malic enzyme (ME), glucose-6-phosphate dehydrogenase
      (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were assayed in livers of
      normal and HCB (100 mg/100 g bw) treated Wistar rats. Mitochondrial LGPD activity
      did not change significantly, however ME, 6GPD and G6PD were induced by HCB only
      in non-thyroidectomized animals. The absence of cytosolic enzymes induction in
      thyroidectomized rats treated with HCB indicates that HCB is not intrinsically
      thyromimetic. The induction of hepatic ME, G6PD and 6PGD activities in HCB
      thyroidectomized rats was dependent on the presence of thyroid hormone. The
      unchanged activity of mitochondrial LGPD in contrast to the increased activities
      of the cytosolic enzymes ME, G6PD and 6PGD is not consistent with a shift in
      functional thyroid status following HCB treatment.

PMID- 7560811
TI  - Simple and reliable method for predicting the remission of Graves' disease:
      revised triiodothyronine-suppression test, indexed by serum thyroxine.
AB  - To find a simple and reliable method for predicting the long-term remission of
      Graves' disease, we studied the outcome of 182 methimazole-treated patients with
      Graves' disease, whose thyroidal RAIU became < 12% after T3 administration. The
      patients were treated with methimazole over 2 years. T3 suppression test was done
      6 months after the disappearance of TSH-receptor antibody (TRAb); the patients
      took T3 for 14 days, and on the 14th day, blood was obtained for serum T3, T4,
      and TSH determination, and RAIU was measured. These 182 patients were followed
      for 5 years after methimazole withdrawal. We divided the 182 methimazole-treated
      patients, whose thyroidal RAIU became < 12% after T3 administration, into two
      groups based on the outcome after the discontinuation of methimazole; 40 patients
      (22%) had an overt recurrence (group A) and the other 142 (78%) did not (group
      B). The degree of serum T4 suppressibility by T3 was less in group A than in
      group B. In group A, the number of the patients with a serum T4 < 60% of the pre
      T3 levels is less than that with a serum T4 > or = 60%, but, in group B the
      former is more than the latter. The serum T4 < 60% of the pre-T3 level was
      significantly associated with the remission.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560809
TI  - Bone mineral metabolism and thyroid replacement therapy in congenital hypothyroid
      infants and young children.
AB  - Impairment of calcium metabolism and low bone density have been found in
      hypothyroid adults. We investigated the effect of thyroid replacement therapy on
      calcium metabolism and bone mineralization in congenital hypothyroid (CH) infants
      and children. One hundred and 16 Caucasian CH consecutive patients were studied
      and were grouped according to their age: 23 patients at diagnosis, 20 at 3 mo, 24
      at 6 mo, 25 at 12 mo and 24 at 36 mo. Thyroid replacement therapy was started at
      an initial dose of 6-8 micrograms/kg/day of L-thyroxine, and then decreased
      progressively. Calcium, phosphorus, magnesium, alkaline phosphatase (AP),
      parathyroid hormone (PTH) and osteocalcin (BGP) were measured as calcium
      metabolism indices. Bone mineral content (BMC) was measured at the mid-portion of
      the right radius AP, PTH and BGP concentrations were significantly higher in
      subjects at 3 mo of age (p < 0.05). This rise coincided with the end of the
      period of maximum dosage of L-thyroxine. Mild asymptomatic hypercalcemia was
      observed in 20 patients. All the other indices did not differ between age groups.
      BMC values and BMC annual increment were not different from those calculated for
      age-matched controls. We found that L-thyroxine replacement therapy does not
      alter bone mineralization of CH infants and children. Only a transitory increase
      of osteoblastic function was observed after the first few months of therapy.

PMID- 7560810
TI  - Thyrotropin binding specificity for the thyrotropin receptor.
AB  - Recently, highly purified bovine thyrotropin (bTSH) of pituitary origin, as well
      as recombinant human (h) TSH free of lutropin (LH) contamination, has been
      reported to activate the LH/choriogonadotropin receptor (LH/CGR). These data
      challenge the concept of TSH specificity for its own receptor. We, therefore, re
      evaluated these data using, as targets, the recombinant hTSH and rat LH/CGRs
      stably expressed in Chinese hamster ovary (CHO) cells. Partially purified bTSH (2
      IU/mg protein) and, to a lesser degree, highly purified bTSH (30 IU/mg protein)
      increased intracellular cAMP levels in CHO-LH/CGR cells (an EC50 of 0.2 and > 20
      mIU/ml, respectively). In contrast, recombinant hTSH (up to 1 IU/ml) did not. All
      three TSH preparations increased cAMP levels to the same extent in CHO-TSHR cells
      (an EC50 of 0.3 mIU/ml). Furthermore, we observed only nonspecific, low affinity
      TSH binding for CHO-LH/CGR cells and also for CHO cells transfected with the
      expression vector alone (a Kd of 100 nM), although both high and low affinity TSH
      binding was demonstrated in CHOT-SHR cells (a Kd of 0.3 and 100 nM,
      respectively). These data indicate that even highly purified bTSH of pituitary
      origin contains significant amounts of LH, and that TSH itself does not appear to
      activate the LH/CGR.

PMID- 7560812
TI  - Infiltrating gamma/delta T-cell receptor-positive lymphocytes in Hashimoto's
      thyroiditis, Graves' disease and papillary thyroid cancer.
AB  - In the present study we have evaluated the expression of different molecular
      forms of the antigen receptor (TcR) on lymphocytes derived from thyroid tissue of
      patients with Graves' disease, Hashimoto thyroiditis and papillary cancer both in
      situ by APAAP technique and on isolated lymphocytes by indirect
      immunofluorescence. A panel of monoclonal antibodies (mAbs) recognizing
      alpha/beta and gamma/delta TcR-positive subsets was used. The results showed that
      the large majority of T-cells in thyroid infiltrates were alpha/beta TcR+,
      gamma/delta TcR+ ones being very rare or nearly absent, whatever the disease
      (autoimmune or neoplastic). No difference between gamma/delta TcR+ T-cell subsets
      (V delta 1+ or V delta 2+) was observed. Thus, neither in autoimmune thyroid
      diseases nor in papillary cancer gamma/delta TcR+ cells are likely to be a major
      effector-T cell population.

PMID- 7560813
TI  - Characterization of insulin autoantibodies in a patient with autoimmune
      hypoglycemia.
AB  - A 60-year-old man referred because of hypoglycemic bouts was found to have
      insulin autoantibodies. Total plasma insulin was as high as 1.44 nmol/l. Both
      plasma free insulin and C-peptide were in the normal range. The indirect
      immunofluorescence technique showed positivity for antinuclear antibodies. The T
      lymphocyte populations in the peripheral blood were normal. When serum binding
      capacity for pork insulin was measured, antibodies binding pork insulin were not
      detected. The patient's serum bound 125I-insulin. The binding protein was
      identified to be an immunoglobulin G. The kinetics of dissociation, studied by
      the Scatchard analysis of the autoantibody, showed a curvilinear plot, which was
      analyzed in two components. Cold human insulin was able to compete with 125I
      insulin for the antibody binding site (I.C.50 = 1.35 nmol/ml). These antibodies
      were apparently not associated with antibodies directed against the insulin
      receptor.

PMID- 7560814
TI  - Fibrous invasive (Riedel's) thyroiditis with critical response to steroid
      treatment.
AB  - The Riedel's thyroiditis is an uncommon form of chronic thyroiditis characterized
      by an invasive fibrosclerosis of the gland, often involving the surrounding
      tissues. Usually, the only possible treatment is the surgical decompression of
      the tissues. We describe a case of aggressive Riedel's thyroiditis with severe
      compression and dislocation of trachea and esophagus. The surgical approach was
      uneffective, while an "ex juvantibus" steroid treatment, resulted in a dramatic
      regression of fibrosclerosis and a complete clinical remission. This report
      points out the possible effectiveness of corticosteroids in the treatment of
      selective disorders involving increased fibrogenesis.

PMID- 7560815
TI  - Thyroiditis due to Brucella melitensis.
AB  - A case of thyroiditis due to Brucella Melitensis is reported. Brucellosis
      anticipated by about two months the onset of the characteristic symptoms of acute
      thyroiditis. Cultures of specimens obtained by fine needle aspiration biopsy and
      microbiological investigations allowed isolation and identification of the germ.
      This observation allowed the recognition that thyroid gland might harbored
      secondary localization of a prolonged brucellosis. A microbiological study (the
      protocol of which is proposed) of specimen obtained by fine needle aspiration
      biopsy should be performed in the presence of symptoms and signs of an
      inflammatory process associated to an acute swelling of the thyroid gland.

PMID- 7560817
TI  - Interviewing older adults: increasing the credibility of interview data.
AB  - 1. Contextual data obtained through open-ended interviewing allows the nurse to
      individualize the nursing care plan and can maximize the nurse's problem solving
      skills. 2. The interviewer who obtains credible data obtains believable data
      which accurately portrays the situation from the subject's point of view. 3.
      Interviewing techniques which can increase self-esteem in the older adult are:
      nonjudgmental wording of questions; providing positive reinforcement; giving the
      individual control; matching gender; allowing time; adapting to hearing and
      vision impairments; and adapting to reading deficits.

PMID- 7560818
TI  - Reducing the use of physical restraints in long-term care facilities.
AB  - 1. There has been increasing recognition of the role of education as a catalyst
      for changing restraint use practices and policies of long-term care facilities in
      Canada and other Western countries. 2. Findings of this longitudinal study
      documented the positive outcome of a structured restraint education program in
      reducing the use of physical restraints and promoting non-restrictive
      alternatives. 3. With continuing education and inservice programs, restraint-free
      elderly care can be attained in a cost-effective manner and without an increase
      in resident falls and injuries.

PMID- 7560816
TI  - Transplantation in diabetes: a cell biological problem.

PMID- 7560819
TI  - Wandering: a proposed definition.
AB  - 1. Two typologies of wandering behavior, "continuous" and "sporadic" can be
      distinguished when time-in-motion is used as a criteria. 2. Interventions for
      "continuous wanderers" should emphasize modification of the environment while
      organized activities and verbal communication techniques should be stressed for
      the "sporadic wanderer." 3. Empirical research is needed that studies the
      different needs of wanderers based on the percentage of time spent in motion.

PMID- 7560821
TI  - Allowing for same sex preferences.

PMID- 7560822
TI  - What successful approaches do you use in dealing with sexually aggressive
      patients/residents?

PMID- 7560820
TI  - TB exposure: are you prepared?
AB  - 1. The elderly have the highest case rates for TB disease. 2. Residents need to
      be screened for TB infection on admission with a Mantoux skin test. 3. Employees
      need to be screened for TB by the Mantoux skin test on hire and annually. 4. A
      chest x-ray is not adequate to screen for TB infection.

PMID- 7560824
TI  - Muto ergo sum. Hepatitis B and the forces of evolution.
AB  - The hepatitis B virus (HBV) polymerase has no editing function and thus
      frequently transcribes its template incorrectly to result in viral variants that
      go under the name of "mutants." These mutants may be viewed as part of a
      continuing Darwinian evolution of HBV with some survival benefit. They also
      result in unusual extrahepatic manifestations of HBV infection, which will
      doubtless continue to divert the hepatologist.

PMID- 7560823
TI  - Multi-modal assessment in Alzheimer's disease. ADL in relation to PET, MRI and
      neuropsychology.
AB  - Alzheimer's disease (AD) causes a deterioration in functional status which may
      best be understood as a multi-dimensional concept. Results of multi-modal
      functional assessment in two patients with probable AD and comparable Mini-Mental
      State Examination scores demonstrated the heterogeneity of disease profiles and
      individual variations in functional status. Measures included direct assessment
      of ADL performance (SAILS), self and family perception of "current" and "best
      ever" functioning (NBFADL-60), neuropsychological test battery, magnetic
      resonance imaging (MRI) and positron emission tomography (FDG-PET). The multi
      modal assessment yielded complementary information, and permitted correlation of
      physiological and behavioral data. Future studies should examine the potential
      heuristic and clinical utility of this approach.

PMID- 7560825
TI  - Gastrointestinal bleeding during low-dose aspirin administration for prevention
      of arterial occlusive events. A critical analysis.
AB  - Low-dose aspirin has been recommended for primary and secondary prevention of
      myocardial infarction and for the maintenance of aortocoronary bypass patency.
      Doses as low as 75 mg/day significantly lessen the risk of stroke or death in
      patients who experience cerebrovascular and ischemic events. Aspirin in
      antiinflammatory doses has been associated with gastrointestinal bleeding, and
      the bleeding potential of even 75 mg aspirin has been established. I assessed the
      role of low-dose aspirin in gastrointestinal bleeding by combining the results of
      nine studies that dealt with the prevention of ischemic, thromboembolic, or
      cerebrovascular events. The combination of the results showed that the occurrence
      of bleeding was 1.5 times higher in patients treated with low-dose aspirin in
      doses of 75-325 mg/day as compared with placebo (odds ratio 1.52; 95% CI 1.32
      1.75). The monthly probability of gastrointestinal bleeding per 1,000 patients
      treated with low-dose aspirin ranged between 0 and 2.1.

PMID- 7560826
TI  - Endoscopic therapy for early gastric cancer. Utility of endosonography and
      evaluation of prognosis.
AB  - We analyzed 30 endoscopically treated patients with early gastric cancer in terms
      of the utility of endoscopic ultrasonography (EUS) and the evaluation of
      prognosis. Endoscopic therapy for early gastric cancer included strip biopsy,
      laser irradiation, and OK-432 injection. Examination of the depth of cancer
      invasion in the strip biopsy specimens showed that the diagnostic accuracy of EUS
      was 85.7%. Complete resection rate in strip biopsy was 82.8%, and the patients
      with incompletely resected cancer were successfully treated with laser
      irradiation and/or OK432 injection. The prognosis of the patients treated with
      strip biopsy was good. Three patients died of causes other than gastric cancer.
      Local recurrence and a heterochronous new lesion developed in six patients, but
      all of these cases were successfully treated with additional strip biopsy. All
      but one patient treated with laser irradiation and/or OK 432 injection survived
      during the study period. These results suggest that EUS is useful in determining
      the indication of endoscopic therapies and that prognosis is good in patients
      with early gastric cancer treated endoscopically.

PMID- 7560827
TI  - Cystic fibrosis and colonic strictures. A new "iatrogenic" disease.
AB  - Excessive dosage of pancreatic enzymes in cystic fibrosis (CF) patients can be
      associated with irreversible colonic stricture. Predisposing factors include a
      young age group, previous intestinal surgery, and prolonged administration of
      high-dose lipase products. Prestricture symptoms include abdominal pain,
      diarrhea, and hematochezia. Pathological signs are ischemic denudation of the
      epithelium with reepithelialization, mild chronic inflammation, and extensive
      collagen synthesis with mural fibrosis. The lesion is distinct from Crohn's
      disease. Its pathophysiological mechanisms remain unknown.

PMID- 7560828
TI  - The effect of the Gulf War on upper-gastrointestinal bleeding.
AB  - Upper-gastrointestinal bleeding may be related to tension or fear, which are
      commonly aggravating factors in digestive diseases. A survey was made of patients
      living in and around Hadera (located in Israel's central coastal region) during
      the Gulf War (January 18 through February 28, 1991) who suffered from upper
      gastrointestinal bleeding; they were compared with patients seen during 1990 and
      1992-1993 at the same time of the year. We found no appreciable difference in the
      rate of upper-gastrointestinal bleeding during the analogous periods covered in
      the survey.

PMID- 7560829
TI  - Biphasic annual periodicity in relapses of inflammatory bowel diseases. Gruppo di
      Studio per le Malattie Infiammatorie Intestinale.
AB  - We evaluate the periodicity in relapses of ulcerative colitis and Crohn's disease
      in this multicenter prospective study. In 275 relapses among 184 patients with
      inflammatory bowel disease, a statistically significant biphasic annual
      periodicity, with peaks in the spring and autumn, was documented only for
      ulcerative colitis relapses (p = 0.006). This finding may be important in
      understanding relapse risk factors and in terms of prevention.

PMID- 7560830
TI  - Colonoscope length and procedure efficiency.
AB  - We reviewed 195 colonoscopies to determine whether procedure efficiency differed
      with the use of an intermediate-length (135 cm) colonoscope compared with a long
      (165 cm) colonoscope. The cecum was intubated with the 135-cm scope in 92.6% of
      procedures and with the 165-cm colonoscope in 96.8% of procedures (chi 2 method,
      p = 0.26). The mean procedure duration was 36.7 min for 107 complete procedures
      performed with the 135-cm colonoscope and 48.4 min for 55 examinations using the
      165-cm colonoscope (t test, p < 0.001). Colonoscopy with the 135-cm instrument
      required mean meperidine and midazolam doses of 59.9 mg and 1.8 mg, respectively,
      compared with doses of 69.1 mg and 2.0 mg, respectively, with the 165-cm
      colonoscope. The differences were not significant. Although the cecal intubation
      rate is slightly less for the 135-cm colonoscope, insertion takes significantly
      less time and is probably more comfortable for the patient than with the 165-cm
      colonoscope.

PMID- 7560831
TI  - Stimulated duodenal/bile juice aspiration for diagnosis of enteric pathogens in
      HIV-infected patients.
AB  - Gastrointestinal and biliary abnormalities are common in the acquired
      immunodeficiency syndrome. Although obviously related to opportunistic infections
      in many cases, often no infectious agent can be identified. The specific
      diagnosis depends on invasive methods such as endoscopic retrograde
      cholangiography and liver histology. To evaluate an alternative and less invasive
      first-line approach, we conducted a prospective study of microscopic examination
      of aspirated duodenal/bile juice, to try to identify microbial causes of human
      immunodeficiency virus (HIV)-related gastrointestinal and biliary tract disease.
      Sixty-four HIV-infected patients underwent upper gastrointestinal endoscopy with
      biopsies from the esophagus, stomach, and duodenum, and aspiration of stimulated
      duodenal/bile juice. Biopsies, duodenal/bile juice, and stool samples were
      examined for enteric pathogens. Twenty-seven intestinal infections were found in
      22 of the 64 patients (34%), 12 (44%) of which were diagnosed by duodenal/bile
      juice examination. Seven of the 27 infections (26%) were diagnosed exclusively in
      duodenal/bile juice, whereas 5 were found in biopsies or stool samples as well.
      Twenty infections (74%) were demonstrated in intestinal biopsies and/or stool
      samples, 15 without any positive result in duodenal/bile juice. The proportion of
      patients with elevated alkaline-phosphatase and gamma-glutamyl-transpeptidase
      activities was higher in patients with infectious agents detected in
      duodenal/bile juice (5 of 11, 45%), than in patients with infectious agents found
      exclusively in intestinal biopsies and/or stool samples (2 of 11, 18%). Analysis
      of duodenal/bile juice is a simple, rapid, and effective method for the detection
      of enteral pathogens in HIV-related gastrointestinal and biliary dysfunction. It
      increases the diagnostic yield above the results of intestinal biopsies and stool
      examinations alone.

PMID- 7560832
TI  - Early interferon therapy and abortion of posttransfusion hepatitis C viral
      infection.
AB  - We studied the role of an "early" 4-month course of interferon therapy on
      posttransfusion viral hepatitis C (PTH-C). Paired serum samples of 51 consecutive
      recipients, taken before and 7-20 days after blood transfusion, were
      prospectively tested for hepatitis C virus ribonucleic acid (HCV RNA) using the
      polymerase chain reaction assay. Seven recipients experienced seroconversion of
      HCV RNA after transfusion. Two of the seven patients underwent an early 4-month
      course of interferon alpha therapy at a dose of 3 mU per day for 5 days during
      the first week, then three times a week for the subsequent 15 weeks. The first
      patient was treated at a very early stage of acute PTH-C and responded well to
      interferon therapy. Acute PTH-C in the second patient was prevented by interferon
      therapy. Both patients had normal serum alanine aminotransferase levels and
      tested negative for anti-HCV and HCV RNA 12 months after the end of treatment.
      Four of the five patients not on interferon therapy developed abnormal serum
      alanine aminotransferase activities more than five times the normal upper limit
      (383 +/- 143 IU/L) at 2-18 weeks after transfusion. All four patients experienced
      seroconversion of anti-HCV, and three patients developed chronic hepatitis. This
      study suggests that early long-term interferon therapy has the potential to
      prevent PTH-C.

PMID- 7560833
TI  - Chronic leukocytoclastic vasculitis complicating HBV infection. Possible role of
      mutant forms of HBV in pathogenesis and persistence of disease.
AB  - A young woman developed arthritis and leukocytoclastic vasculitis, followed by
      hepatitis due to a precore mutant strain of hepatitis B virus (HBV) incapable of
      synthesizing HBe antigen. Tests for antibodies to HCV were persistently negative.
      Treatment of the patient with alpha interferon initially led to a severe
      exacerbation of hepatitis. Later, higher doses of interferon were tolerated and
      were associated with reduction of HBV replication and improvement in liver
      histopathology and serum aminotransferases. After interferon therapy, sequencing
      of HBV DNA from a repeat liver biopsy showed a cluster of new mutations, which
      may have led to alterations in immunodominant epitopes of viral proteins. The
      findings suggest that a "naturally occurring" mutant form of HBV was associated
      with chronic hepatitis and vasculitis in the patient, and that the immunological
      pressure on HBV produced by therapy with interferon may have led to other
      mutations in the viral genome with persistence of low-level HBV infection.

PMID- 7560834
TI  - Evolving strategies for the treatment of adenocarcinoma of the pancreas. A
      review.
AB  - Adenocarcinoma of the pancreas has an incidence of only 0.01%, yet is the fourth
      leading cause of cancer death for American men and women. Despite this dismal
      outlook, new strategies for staging and therapy for pancreatic cancer have
      emerged over the last few years. Laparoscopy with cytologic evaluation of
      peritoneal washings, and more recently, although still investigational,
      endoscopic and intracorporeal ultrasonography have provided more detailed staging
      information. The result of improved staging is earlier, more accurate selection
      of treatment most appropriate for stage of disease. For those patients with
      clinically localized disease, laparotomy with an attempt at resection is
      indicated, particularly with the recent trend in declining morbidity and
      operative mortality the recent trend in declining morbidity and operative
      mortality associated with pancreatectomy. With clinically unresectable disease,
      patients may potentially be spared the morbidity of laparotomy. Advances in
      therapeutic endoscopic and percutaneous manipulation of the obstructed biliary
      tree have provided an alternative to surgery and improved quality of life for
      patients with abbreviated life spans. Gastroduodenal obstruction has
      traditionally been managed by laparotomy, although with improved technology and
      surgical skill, a laparoscopic approach may become standard. Because even at
      presentation pancreatic cancer is rarely a localized process but is a
      disseminated disease, surgery alone is unlikely to increase survival rates in the
      absence of adjuvant therapies. Present and future strategies for treatment
      include the addition of neoadjuvant regimens and adjuvant modalities including
      intraoperative radiation, photodynamic therapy, intraperitoneal therapies, and
      pancreatic and splanchnic perfusion. Clearly, the greatest strides in treatment
      of pancreatic cancer will come with development of new agents with significantly
      greater antitumor efficacy.

PMID- 7560835
TI  - Disinfectant colitis. Rinse as well as you wash.
AB  - Commercially available endoscope disinfecting solutions readily cause colonic
      damage if allowed to contact mucosa. The two most common cleaning solutions
      differ in their initial toxic effect (glutaraldehyde directly injuries crypt
      epithelium, and hydrogen peroxide compromises mucosal stroma), but both
      ultimately result in tissue necrosis over time. Within 12-48 h after colonoscopy,
      patients show signs of bloody diarrhea, cramping, and fever--symptoms that may be
      confused with an infectious process. Based on a literature review and our own
      experimental studies, we conclude that hydrogen peroxide alone is responsible for
      a unique form of colitis commonly referred to as pseudolipomatosis by
      pathologists. This controversial lesion becomes visible as opaque plaques or
      pseudomembranes even while colonoscopy is in progress and is almost assuredly due
      to the effervescent release of molecular oxygen. Diligent rinsing is necessary to
      minimize patients' exposure to residual disinfecting chemicals in the endoscope.
      When an automatic disinfecting machine is employed, it may require strict
      adherence to proper maintenance and volume adjustments in the rinse cycle. Forced
      air drying and an additional preprocedure rinse of channels and the exterior of
      the scope should ensure a chemical-free examination.

PMID- 7560836
TI  - Lack of correlation between diarrhea and weight loss in HIV-positive outpatients
      in Houston, Texas.
AB  - To determine the prevalence of diarrhea and weight loss among human
      immunodeficiency virus (HIV)-positive patients, we reviewed the records of all
      patients attending the Harris County HIV Clinic during a 4-month time period.
      Diarrhea was considered persistent if it had been present for > 14 days or on two
      or more consecutive clinic visits. Weight loss was defined as moderate (5-10%
      reduction in weight) or severe (> 10% reduction) when the present weight was
      compared with the weight found at the initial clinic visit. Records were reviewed
      for 1,370 patients, of whom 12.2% complained of diarrhea (7.7% acute and 4.5%
      persistent). Diarrhea was more common among patients with a history of male-to
      male sexual contact than in patients with other HIV risk factors (p < 0.003 for
      acute and p < 0.006 for persistent). The mean CD4 cell count was not
      significantly different in patients with or without persistent diarrhea (176
      versus 212) or acute diarrhea (215 versus 212). Weight loss was reported in 25.2%
      of subjects (12.8% moderate and 12.4% severe). It did not correlate with CD4
      count. Persistent diarrhea also was not associated with weight loss. Acute and
      persistent diarrhea were common among ambulatory HIV-positive patients,
      particularly in homosexual men. We did not identify a correlation among diarrhea,
      weight loss, and CD4 count. Thus, factors other than chronic diarrhea and
      immunosuppression appear to be responsible for weight loss in HIV-infected
      patients.

PMID- 7560837
TI  - Cancer chemotherapy in the elderly.
AB  - Gastrointestinal malignancies are very common in the elderly of the U.S. There is
      controversy about the role of chemotherapy in these elderly patients because of
      the impression that this population experiences greater toxicity while deriving
      lesser benefit. Though definitive data is lacking regarding many aspects of
      chemotherapy in the elderly, some general observations can be made: (a) most
      chemotherapy agents do not have increased toxicity in the elderly; (b) dosing and
      regimen should be based more on functional parameters rather than chronologic
      age; (c) chemotherapy for advanced gastrointestinal malignancies is in general of
      marginal efficacy and can be potentially toxic, regardless of age; and (d) better
      prospective studies focusing on the efficacy, toxicity, and quality of life
      effects of chemotherapy in the elderly should be performed. We review the
      literature regarding chemotherapy pharmacology, efficacy, and organ-specific
      toxicity of agents used in gastrointestinal malignancies in the context of these
      principles.

PMID- 7560838
TI  - Duodenal duplication cyst with massive gastrointestinal bleeding.

PMID- 7560839
TI  - Colosplenic fistula and splenic abscess complicating Crohn's colitis.

PMID- 7560840
TI  - Splenic abscess associated with Pasteurella multocida in an immunocompetent
      patient.

PMID- 7560841
TI  - Intrahepatic arterioportal fistula stemming from percutaneous biliary drainage:
      unusual cause of postoperative massive hemobilia.

PMID- 7560842
TI  - Esophageal melanosis.

PMID- 7560843
TI  - Time for creative integration in medical sociology.
AB  - The burgeoning of medical sociology has sometimes been accompanied by unfortunate
      parochialism and the presence of opposing intellectual camps that ignore and even
      impugn each other's work. We have lost opportunities to achieve creative
      discourse and integration of different perspectives, methods, and findings. At
      this stage we should consider how we can foster creative integration within our
      field.

PMID- 7560844
TI  - Women's health research: public policy and sociology.
AB  - In the space of just a few years, the amount and nature of scientific research on
      women's health has emerged as a major policy issue being addressed at the highest
      levels of the federal government and in the mainstream media. This debate has
      engaged members of Congress, the National Institutes of Health, and other federal
      agencies, and medical, scientific, health, and women's organizations.
      Sociologists have made significant contributions to both the process by which the
      women's health research issue has ascended to public awareness and the content of
      its agenda. Many of these contributions go unrecognized and other potential
      contributions by medical sociologists remain unrealized. In order to advance both
      science and practice in women's health--by ensuring the inclusion of the
      sociological perspective--we encourage sociologists to participate more directly
      in the policy debates.

PMID- 7560845
TI  - Professional dynamics and the changing nature of medical work.
AB  - The organization and delivery of health care in the United States is undergoing
      significant social, organizational, economic, political, and cultural changes
      with important implications for the future of medicine as a profession. This
      essay will draw upon some of these changes and briefly review major sociological
      writings on the nature of medicine's professional status to examine the nature of
      professional dynamics in a changing environment. To this end, we focus on the
      nature of medical work and how this work impacts on and is impacted by medicine's
      own internal differentiation and the presence of contested domains at medicine's
      periphery. We trace this dynamic through a number of issues including the
      multidimensional nature of medical work, the role of elites in that work, and how
      changes in the terms and conditions of work can exert changes at medicine's
      technical core. We close with some thoughts on the relationship of public policy
      to medicine's professional status, the role health policy might take in shaping a
      new professional status, the role health policy might take in shaping a new
      professional ethnic for medicine, and the role sociologists might play in this
      process.

PMID- 7560846
TI  - Through the lenses of organizational sociology: the role of organizational theory
      and research in conceptualizing and examining our health care system.
AB  - This paper reviews various theoretical perspectives on organizational change
      which have been and could be applied to medical organizations. These perspectives
      are discussed as both filters influencing our observations (research) and mirrors
      of the shifting dynamics of delivery system reform (policy). We conclude with an
      examination of how such theories can provide useful insights into our rapidly
      changing health care system.

PMID- 7560847
TI  - Medical sociology and health policy: where are the connections?
AB  - The attempt to assess the impact of medical sociology on health policy encounters
      operational difficulties regarding what should be counted. After reviewing these
      difficulties, we argue that there is potential interest among policymakers for
      sociological contributions to policy debates, but that policy impact has been
      limited by sociologists' ambivalence, academic career considerations, and by
      health research becoming a distinct field of research. Suggestions for increasing
      sociologists' policy impact include attending to policy relevance in both the
      design of studies and the dissemination of results and by sociologists' becoming
      more oriented to the field of health policy research.

PMID- 7560848
TI  - Naming and framing: the social construction of diagnosis and illness.
AB  - This paper examines the social construction of diagnosis and illness in several
      ways. First, I discuss the centrality of social construction in medical
      sociology. Next I discuss the major role of diagnosis in social construction,
      leading to the need for a sociology of diagnosis. I emphasize controversial and
      conflictual diagnoses, as a first step toward a more general sociology of
      diagnosis. Then I put forth a typology of social construction, involving four
      combinations based on whether a condition is generally accepted and whether a
      biomedical definition is applied. Next I detail a series of stages in the social
      construction of a condition. In that process, my primary concern is the initial
      social discovery, which is essentially a matter of diagnosis, with a secondary
      emphasis on illness experience. This is followed by stages of treatment and
      outcome, which recursively affect social construction. I conclude by noting the
      health policy implications of the social constructionist perspective.

PMID- 7560849
TI  - Health, illness, and healing in an uncertain era: challenges from and for medical
      sociology.
AB  - The current situation in health care organizations, among providers and for
      people, dramatically challenges the "business as usual" roles of medicine,
      government, insurance companies, the community, and the university. Health care
      reform marks the first attempt in a century to consider a reconstruction of the
      social contract between society and medicine. While sociology stands as one of
      the earliest social sciences to systematically study the health care arena and
      create a health-focused subfield, there is a perception, not without support, of
      a desertion of identity from within, an encroachment by other areas from without,
      and abandonment by the parent discipline. We argue that these situations in
      medical arenas and in research fields require serious rethinking. The key lies in
      understanding how these phenomena are related to each other and to larger social
      forces, and how they offer opportunities, rather than signal limitations, to
      medical sociologists. We turn to the theoretical tools of sociology to help
      unravel the complicated challenges that face both policymakers and researchers.
      After framing these issues in a sociology of knowledge perspective, we use the
      case of "utilization theory" to illustrate the connections between society and
      systems of care (as well as studies of them) and to create a future agenda. We
      end by raising three basic questions: (1) Why is a sociological perspective
      critical to the understanding of change and reform in health care? (2) Why is
      medical sociology critical to the survival of the general sociological
      enterprise? and (3) Why is general sociology critical to the research agenda in
      medical sociology?

PMID- 7560850
TI  - Stress, coping, and social support processes: where are we? What next?
AB  - I review existing knowledge, unanswered questions, and new directions in research
      on stress, coping resource, coping strategies, and social support processes. New
      directions in research on stressors include examining the differing impacts of
      stress across a range of physical and mental health outcomes, the "carry-overs"
      of stress from one role domain or stage of life into another, the benefits
      derived from negative experiences, and the determinants of the meaning of
      stressors. Although a sense of personal control and perceived social support
      influence health and mental health both directly and as stress buffers, the
      theoretical mechanisms through which they do so still require elaboration and
      testing. New work suggests that coping flexibility and structural constraints on
      individuals' coping efforts may be important to pursue. Promising new directions
      in social support research include studies of the negative effects of social
      relationships and of support giving, mutual coping and support-giving dynamics,
      optimal "matches" between individuals' needs and support received, and properties
      of groups which can provide a sense of social support. Qualitative comparative
      analysis, optimal matching analysis, and event-structure analysis are new
      techniques which may help advance research in these broad topic areas. To enhance
      the effectiveness of coping and social support interventions, intervening
      mechanisms need to be better understood. Nevertheless, the policy implications of
      stress research are clear and are important given current interest in health care
      reform in the United States.

PMID- 7560851
TI  - Social conditions as fundamental causes of disease.
AB  - Over the last several decades, epidemiological studies have been enormously
      successful in identifying risk factors for major diseases. However, most of this
      research has focused attention on risk factors that are relatively proximal
      causes of disease such as diet, cholesterol level, exercise and the like. We
      question the emphasis on such individually-based risk factors and argue that
      greater attention must be paid to basic social conditions if health reform is to
      have its maximum effect in the time ahead. There are two reasons for this claim.
      First we argue that individually-based risk factors must be contextualized, by
      examining what puts people at risk of risks, if we are to craft effective
      interventions and improve the nation's health. Second, we argue that social
      factors such as socioeconomic status and social support are likely "fundamental
      causes" of disease that, because they embody access to important resources,
      affect multiple disease outcomes through multiple mechanisms, and consequently
      maintain an association with disease even when intervening mechanisms change.
      Without careful attention to these possibilities, we run the risk of imposing
      individually-based intervention strategies that are ineffective and of missing
      opportunities to adopt broad-based societal interventions that could produce
      substantial health benefits for our citizens.

PMID- 7560852
TI  - Medical sociology and the study of severe mental illness: reflections on past
      accomplishments and directions for future research.
AB  - Over the past 40 years, the mental health care system has been radically
      transformed from one focused on institutionalized care to one centered on
      treatment in community settings. While medical sociology has played a prominent
      role in the study of psychiatric hospitalization and the deinstitutionalization
      process, the systematic exploration of the sociological dimensions of community
      based mental health care is only just beginning. This essay reflects on past
      disciplinary contributions and explores some important empirical and theoretical
      directions in the field of mental illness research that could benefit from more
      extensive sociological analysis. The central argument is that the shift to a
      community-based mental health system has increased the need for the sociological
      perspective and that medical sociologists, in particular, have the theoretical
      and analytical perspective essential for developing a more complete understanding
      of the current conditions impacting the lives of people with severe mental
      disorders. Drawing on recent work in medical sociology, we illustrate some
      important topical areas at the center of controversies over treatment, social
      change, and public policy regarding severe mental illness. We conclude with a
      discussion of the barriers to this type of sociological research and suggestions
      for ways medical sociologists might contribute to the study of severe mental
      disorders in the future.

PMID- 7560853
TI  - Detection of hepatitis E virus genome and gene products in two patients with
      fulminant hepatitis E.
AB  - Non-isotopic in situ hybridization (digoxigenin-labeled probe directed towards
      hepatitis E virus ORF1) and immunohistochemistry (against hepatitis E virus ORF2
      and ORF3) were applied to detect hepatitis E virus genome and gene product in the
      liver tissue of two patients with fulminant hepatitis E seropositive for
      hepatitis E virus RNA. Both hepatitis E virus RNA and hepatitis E virus antigens
      were detected exclusively in the cytoplasm of hepatocytes and not detected in
      other cell types. In both patients, more than 50% of the hepatocytes were
      positive for both hepatitis E virus RNA and hepatitis E virus antigens, most of
      which showed degenerative changes. This is consistent with the histological
      appearance of marked loss of hepatocytes with acinar collapse. Interestingly,
      denaturation of the RNA before in situ hybridization was found to enhance
      hepatitis E virus RNA detection. We conclude that: (1) hepatitis E virus RNA and
      hepatitis E virus antigens can be demonstrated in the liver in hepatitis E virus
      related fulminant hepatitic failure, (2) hepatitis E virus is hepatocyte-tropic
      within the liver, (3) cytoplasmic localization of hepatitis E virus RNA and
      hepatitis E virus antigens is consistent with cytoplasmic replication, and (4)
      the presence of degenerative changes in hepatitis E virus positive cells,
      together with the histological appearance of hepatocyte loss in the absence of
      significant inflammatory infiltrate, suggests that hepatitis E virus-related
      fulminant hepatitic failure is mediated by a cytopathic mechanism.

PMID- 7560854
TI  - Prevalence of thyroid autoantibodies is not increased in blood donors with
      hepatitis C virus infection.
AB  - Serum autoimmune reactions are found in many patients with hepatitis C. A high
      prevalence of thyroid dysfunction and antithyroid antibodies in patients with
      chronic hepatitis C was recently reported. We have compared the prevalence of
      thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with
      hepatitis C virus (HCV) infection (study group) and in seronegative anti-HCV
      donors (control group). One hundred and ninety-two blood donors were studied: 96
      were anti-HCV positive by ELISA 2 (48 males and 48 females; age 48 +/- 12.9
      years, mean +/- SD), and 96 were HCV seronegative (55 males and 41 females; age
      37 +/- 14.8 years). In all patients, serum TSH (0.25-4.2 mU/l) and fT4 (9-23
      pmol/l) were measured by immunochemiluminiscent assays and antithyroid peroxidase
      antibodies (normal < 100 U/ml) by RIA. In all anti-HCV positive donors, hepatitis
      C viremia was tested using the nested polymerase chain reaction. Thyroid
      dysfunction was found in three females (3.1%) in the anti-HCV positive group
      (three cases of hypothyroidism), and in four (4.1%) anti-HCV negative blood
      donors (three cases of hypothyroidism, two females and one male; one case of
      hyperthyroidism, a female), (p = NS). Antithyroid peroxidase antibody titers were
      above normal values in 5 (5.2%) anti-HCV positive individuals and in eight (8.3%)
      anti-HCV negative blood donors (p = NS). These results do not show an increase
      prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood
      donors with HCV infection when compared with a control group.

PMID- 7560855
TI  - Androgen receptors in hepatocellular carcinoma and surrounding liver:
      relationship with tumor size and recurrence rate after surgical resection.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the parameters associated with the
      presence of androgen receptors in hepatocellular carcinoma and surrounding non
      tumoral liver. Furthermore, we have assessed whether androgen receptor positivity
      influences disease recurrence after surgical resection. METHODS: Androgen
      receptor concentration was calculated by receptor binding assay in tumoral and
      non-tumoral liver in 43 patients (40 of them with cirrhosis) with hepatocellular
      carcinoma who underwent surgical resection. RESULTS: Androgen receptors were
      found in 28 of the tumoral and in 30 of the non-tumoral samples, at
      concentrations ranging between 5 and 211 fmol/mg protein. The presence of
      androgen receptors within the tumor was significantly related to a smaller tumor
      size. Thereby, 22 of the 29 nodules < or = 3 cm contained androgen receptors,
      while this occurred in only six of the 14 tumors larger than 3 cm (p < 0.05). In
      contrast, the only parameter associated with the presence of androgen receptors
      in the non-tumoral liver was a lower gamma-glutamyltranspeptidase concentration.
      Disease recurrence after surgical resection was not only related to some tumor
      characteristics (increased alfa-fetoprotein concentration, presence of
      satellites, differentiation degree), but also to the presence of androgen
      receptors in the surrounding liver. Thus, the probability of recurrence after 1-
      and 2-year follow up in patients with androgen-positive livers was 33% and 50%,
      respectively, while it was 0% and 20% in those with androgen-negative livers (p <
      0.05). In contrast, the presence of androgen receptors within the tumor was not
      associated with a higher recurrence rate. CONCLUSIONS: These results show that
      only two thirds of hepatocellular carcinomas contained androgen receptors and
      that this feature was more frequent in small tumors. In addition, our data
      indicate that the presence of androgen receptors within the tumor does not imply
      a different outcome after surgical resection. In contrast, the presence of these
      receptors in the surrounding non-tumoral liver may be considered a risk factor
      for a higher incidence of disease recurrence.

PMID- 7560856
TI  - Vascular complications in living related liver transplantation detected with
      intraoperative and postoperative Doppler US.
AB  - BACKGROUND/AIMS: The purpose of this study was to clarify changes in the graft
      hemodynamics induced by vascular complications in living related liver
      transplantation. METHODS: This study included 46 pediatric recipients who
      underwent partial liver transplantation from living related donors. The blood
      flow was evaluated in the portal system, the hepatic artery and the hepatic vein
      with serial intra- and post-operative Doppler ultrasound (US). RESULTS: In 12
      patients, intraoperative Doppler US showed a decrease in portal venous inflow (<
      9 ml.min-1.kg-1) toward the liver graft and could act as a guide for ligation of
      collaterals in seven patients, portal re-construction in two, thrombectomy in one
      and relief of hepatic venous outflow obstruction in two for increasing the portal
      venous inflow. In five patients, intraoperative Doppler US showed poor arterial
      inflow, i.e. dampened arterial waveforms which involved both low pulsatility
      index (< 0.90) and low peak-systolic velocity (< 31 cm/s). In three of them, the
      waveform was more pulsatile after re-anastomosis or relief from stretching of the
      hepatic artery. The remaining two patients developed hepatic artery thrombosis.
      Most of the hepatic venous outflow obstruction (four of five patients) had flat
      waveforms, low flow velocity (< 10 cm/s) of the hepatic vein, and poor portal
      inflow (flow velocity < 14 cm/s). Postoperative Doppler US showed hepatic venous
      outflow obstruction in three patients, hepatic artery thrombosis in three (twice
      in one patient), portal vein stenosis in two and portal vein thrombosis in one.
      These complications were successfully managed with surgical procedures in three
      patients, transhepatic angioplasty in three and conservative treatments in four.
      Six patients died of non-vascular complications. CONCLUSIONS: Serial intra- and
      post-operative Doppler US was a useful technique for making an early diagnosis of
      abnormal hemodynamics of the graft circulation. Furthermore, intraoperative
      Doppler US could assess reconstructed vessels objectively and would reduce the
      incidence of vascular complications following transplantation.

PMID- 7560857
TI  - Peptic ulcer and its course in cirrhosis: an endoscopic and clinical prospective
      study.
AB  - The epidemiological and clinical characteristics of peptic ulcer were studied in
      324 of 368 consecutive patients with cirrhosis of the liver during a mean period
      of 1.2 (+/- 0.61) years. Peptic ulcer prevalence rates in patients with cirrhosis
      were as follows: point prevalence 11.7%, period prevalence 15.1%, and life-time
      prevalence 24.2%. The annual incidence rate observed in 140 patients with
      cirrhosis undergoing endoscopic follow up was 4.3%. Ulcers were asymptomatic in
      more than 70% of patients. The peptic ulcer complication rate at entry was 20% in
      the whole group and 40% in those who had not a previous diagnosis of peptic ulcer
      when admitted to the study. Peptic ulcer was more frequent among HBsAg+
      cirrhotics (p = 0.05). Patients with more severely decompensated cirrhosis also
      had a higher frequency of asymptomatic ulcers (p = 0.04), gastric ulcers (p =
      0.01) and asymptomatic gastric ulcers (p = 0.005). After diagnosis, during
      endoscopic follow up, gastric ulcer in patients with cirrhosis tended to heal
      slowly and recurred with higher frequency than in controls without cirrhosis (p =
      0.04). Seventy-nine per cent of peptic ulcer recurrences were asymptomatic in
      patients with cirrhosis. There were no complications during the follow-up period:
      this could be due to the regular timing of endoscopy, which permitted early
      detection and treatment of the recurrences, thus preventing further
      complications.

PMID- 7560858
TI  - Lamellar bodies coexist with vesicles and micelles in human gallbladder bile.
      Ursodeoxycholic acid prevents cholesterol crystal nucleation by increasing
      biliary lamellae.
AB  - The aggregative forms of lipids in human gallbladder bile and their relation to
      cholesterol crystallization are controversial. Using combined chemical, gel
      chromatographic, optical/electron microscopic and quasielastic light-scattering
      methods, we investigated this issue in native gallbladder bile obtained from nine
      untreated cholesterol gallstone patients and eight cholesterol gallstone patients
      treated for 1 week with 600 mg/day of ursodeoxycholic acid. Bile obtained at
      cholecystectomy was ultracentrifuged for 2 h at 150,000 g to obtain isotropic
      samples. The conventional cholesterol crystal observation time was 3.1 +/- 4.1
      (SD) days in controls and 19.0 +/- 1.9 days in the ursodeoxycholic acid-treated
      group (p < 0.001). Bile was analyzed by high-resolution gel-chromatography using
      7 mM sodium taurocholate in the elution buffer. Biliary lipids eluted in four
      chromatographic zones: zone #I, corresponding to the column void volume,
      contained only minimal amounts of lipids; zone #II (apparent m.w. 100-220 kDa)
      comprised 29.1 +/- 12.4% of biliary cholesterol in the untreated group and 8.3 +/
      4.3% in the ursodeoxycholic acid-group (p < 0.001). At negative staining
      electron microscopy, this region was composed of roundish vesicles ranging from 7
      to 20 nm in diameter. Zone #III (apparent m.w. 50-100 kDa) carried 59.1 +/- 2.1%
      of cholesterol in untreated patients and 81.2 +/- 9.5% in ursodeoxycholic acid
      rich biles, respectively (p < 0.001). At negative staining electron microscopy,
      this region was composed of lamellar stacks of variable length, usually with 5 nm
      interspaces and up to 30 nm in width. In ursodeoxycholic acid-rich biles,
      lamellae often appeared in the form of concentric fingerprint-like images.
      Quasielastic light-scattering measurements in this region were compatible with
      the size estimates obtained at electron microscopy. Zone #IV (apparent m.w. 6-50
      kDa) carried 11.8 +/- 9.4% and 11.6 +/- 9.0% of cholesterol, respectively (not
      significant). Since this region comprised a considerable fraction of endogenous
      bile salts and had no distinct morphological structures, it was interpreted as
      mixed micelles. The cholesterol crystal observation time showed a significant
      inverse correlation (r = -0.85, p < 0.001) with percent cholesterol carried by
      vesicles (zone #II) and a direct correlation (r = 0.86, p < 0.001) with percent
      cholesterol carried by lamellar bodies (zone #III). Vesicles and lamellae
      identical to those observed in isolated gel-chromatographic fractions were
      observed also on direct electron microscopic examination of unfractionated
      isotropic native biles. Similar findings were observed also in matched model
      biles.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7560860
TI  - A long-term study of the interaction between iron and alcohol in an animal model
      of iron overload.
AB  - BACKGROUND/AIMS: The hypothesis that chronic alcohol ingestion potentiates iron
      associated liver injury was investigated in the 'carbonyl iron-overload rat
      model'. METHODS: Newborn male and female Wistar-Furth rats (seven per group) were
      used to investigate iron-alcohol interaction over a 26-week period. Groups 1 and
      2 were iron loaded from birth, while the others received normal diet. At 10 weeks
      all rats commenced Lieber-DeCarli liquid diet; additional treatments were: group
      1 6 g carbonyl iron/1000 ml diet plus alcohol; group 2 carbonyl iron in the
      liquid diet; group 3 alcohol in the liquid diet; group 4, the controls, received
      liquid diet only. RESULTS: This study confirmed our previous observation that
      iron-loading from birth resulted in grade III-IV siderosis, in both male and
      female rats, and caused fibrosis associated with periportal macrophages. Alcohol
      feeding, in addition to iron-feeding for 26 weeks significantly lowered the
      hepatic iron concentration in both male and female rats compared to those fed
      iron only (p < 0.05). Alcohol feeding did increase hepatic fibrosis in the iron
      loaded animals. However, serum alanine aminotransferase activity was
      significantly higher in the iron-alcohol group than in the other groups (p <
      0.05). CONCLUSIONS: Thus, contrary to expectation, chronic alcohol feeding failed
      to potentiate hepatic fibrosis in iron-overloaded rats, although there was rather
      more hepatocyte necrosis, and the serum alanine aminotransferase activity was
      significantly higher in the iron-alcohol group than in the other groups.

PMID- 7560859
TI  - Enhanced biliary excretion of canalicular membrane enzymes in estrogen-induced
      and obstructive cholestasis, and effects of different bile acids in the isolated
      perfused rat liver.
AB  - BACKGROUNDS/AIMS: Canalicular membrane enzymes are normally released into bile by
      partially known processes. This study was undertaken to investigate whether
      hepatocellular cholestatis induced in rats by ethynylestradiol or obstructive
      cholestasis produced by complete biliary obstruction for 24 h is associated with
      an increased release of alkaline phosphatase and gamma-glutamyl transpeptidase
      into bile, and to clarify how this process is affected by different bile acids.
      METHODS: The studies were performed in the isolated perfused liver during
      infusion of sodium taurocholate, taurochenodeoxycholate and tauroursodeoxycholate
      at increasing rates. RESULTS: Maximum sodium taurocholate, taurochenodeoxycholate
      and tauroursodeoxycholate secretory rates were decreased in both cholestatic
      groups (complete biliary obstruction > ethynylestradiol) compared with controls.
      Maximum biliary outputs of alkaline phosphatase and gamma-glutamyl transpeptidase
      were significantly increased in the ethynylestradiol group during infusion of
      sodium taurocholate and taurochenodeoxycholate, but not of tauroursodeoxycholate,
      and were increased in the complete biliary obstruction group during the infusion
      of sodium taurocholate and tauroursodeoxycholate but not of
      taurochenodeoxycholate. The biliary outputs of alkaline phosphatase and gamma
      glutamyl transpeptidase showed a significant and direct linear relationship with
      sodium taurocholate and taurochenodeoxycholate secretory rates in both
      cholestatic groups. However, only in the complete biliary obstruction group did
      alkaline phosphatase and gamma-glutamyl transpeptidase excretion show a
      significant correlation with tauroursodeoxycholate secretory rates. The slope of
      the line, which indicated the mU of enzyme activity secreted per nmol of sodium
      taurocholate or taurochenodeoxycholate, was greater for gamma-glutamyl
      transpeptidase and alkaline phosphatase in both cholestatic groups
      (ethynylestradiol > complete biliary obstruction) than in the control group.
      Alkaline phosphatase activity in purified isolated canalicular and sinusoidal
      membranes was significantly increased in both cholestatic groups (complete
      biliary obstruction > ethynylestradiol), while gamma-glutamyl transpeptidase
      activity was unchanged compared with controls. CONCLUSION: The marked increase in
      sodium taurocholate and taurochenodeoxycholate-mediated release of alkaline
      phosphatase and gamma-glutamyl transpeptidase into bile in cholestatic rats
      suggests an increased lability of these intrinsic membrane proteins to the
      detergent effects of secreted bile acids. It remains to be elucidated whether
      this phenomenon, which was particularly intense in ethynylestradiol induced
      cholestasis, is important in the pathogenesis and perpetuation of bile secretory
      failure. In contrast, tauroursodeoxycholate administration did not result in
      enhanced biliary excretion of these membrane enzymes, in either the control group
      or the ethynylestradiol group, supporting the concept that this bile salt lacks
      the membrane toxicity of common bile acids.

PMID- 7560861
TI  - Effects of propranolol on intestinal microcirculation of normal and portal
      hypertensive rats.
AB  - BACKGROUND/AIMS: The goal of the present study was to compare the efficacy of
      locally and systemically administered propranolol in normal and prehepatic portal
      hypertensive rats, and to test the hypothesis that beta-adrenoceptor blockade
      reduces intestinal arteriolar diameter by allowing unopposed alpha-adrenergic
      activity. METHODS: The small intestine was prepared for in vivo microcirculatory
      studies and transferred to an intravital microscope where arteriolar diameter and
      erythrocyte velocity were continuously monitored. First order arteriolar (1A)
      blood flow was calculated from the product of mean velocity and microvessel cross
      sectional area. In separate experiments, diameter responses of 2A and 3A were
      monitored. Once steady-state conditions were achieved, the preparation was
      challenged by topically applied doses of propranolol (0.01-100.00 microM) in the
      presence and absence of the alpha-receptor antagonist, phentolamine. In a
      separate group of experiments, the effects of systemically administered
      propranolol (10 mg/kg body weight) were evaluated before and after local alpha
      adrenoceptor blockade. RESULTS: Propranolol produced significant vasoconstriction
      and decreased blood flow in both normal and portal hypertensive rats. Portal
      hypertensive arterioles exhibited an attenuated response to propranolol. Local
      administration of phentolamine completely blocked the propranolol-induced
      diameter changes. Comparison of equivalent concentrations of local and systemic
      propranolol indicated that both routes of administration were equally effective.
      CONCLUSION: The results of the present study suggest that the cardiovascular
      actions of propranolol are predominantly mediated through blockade of peripheral
      beta 2-adrenoceptor.

PMID- 7560862
TI  - Fatal necrotizing pancreatitis caused by hepatitis B virus infection in a liver
      transplant recipient.
AB  - A 32-year-old man who had undergone liver transplantation for fulminant hepatitis
      due to HBV infection developed fatal acute necrotizing pancreatitis on the 60th
      post-transplant day, while showing signs of intense viral replication.
      Immunohistochemistry and in situ hybridization of the pancreas following autopsy
      showed the presence of HBsAG and HBV-DNA in the cytoplasm of acinar cells,
      together with the picture of necrotizing pancreatitis. Clinical and histological
      features seem to indicate that pancreatitis was directly caused by HBV infection.

PMID- 7560864
TI  - Histological grading and staging of chronic hepatitis.

PMID- 7560863
TI  - Molecular epidemiology of hepatitis C virus infection among intravenous drug
      users.
AB  - BACKGROUND/AIMS: The clinico-pathological features of hepatitis C virus infection
      in intravenous drug users are different from those found in other hepatitis C
      virus-infected patients. Our aim was to test whether specific viral variants
      circulate within this particular patient population. METHODS: We studied the
      distribution of hepatitis C virus genotypes in 90 drug addicts and 484 controls,
      according to the method described by Okamoto. RESULTS: Hepatitis C virus type 1a
      and 3a infections were more frequent among intravenous drug users than in 125 age
      matched controls (48.8% and 21.1% vs 17.6% and 11.2%), accounting for the
      majority of infections in intravenous drug users. Analysis of hepatitis C virus
      genotypes according to age showed that, in the general population, hepatitis C
      virus types 1a and 3a were more prevalent among patients younger than 40 years of
      age than in older individuals (17.6% and 11.2% vs 1.4% and 0.6%). CONCLUSIONS:
      These findings suggest that hepatitis C virus types 1a and 3a were recently
      introduced in Italy, presumably via needle-sharing among intravenous drug users,
      and from this reservoir they are extending to the general population,
      particularly among younger subjects.

PMID- 7560865
TI  - Hepatic stellate (ITO) cells: expanding roles for a liver-specific pericyte.

PMID- 7560867
TI  - Prospective screening for hepatocellular carcinoma: a debated issue.

PMID- 7560866
TI  - Relationship between the presence of circulating anti-GOR and hepatitis C
      viremia/genotype.

PMID- 7560868
TI  - Old and new concepts for the role of chi in bacterial recombination.
AB  - The DNA sequence 5'[GCTGGTGG]3', which is called chi, stimulates recombination
      that is mediated by the RecBCD pathway of Escherichia coli. In 1981, a model was
      proposed in which the RecBCD enzyme enters DNA at a double-chain end. The enzyme
      then travels between the chains by unwinding and rewinding the DNA at different
      rates so that the traveling enzyme becomes encumbered by a region of unwound DNA.
      Upon meeting chi, the enzyme was supposed to cut one of the two unwound chains,
      generating thereby a recombinagenic single-chain end. The model, based on
      microscopical observations of RecBCD enzyme interacting with linear duplex DNA,
      was supported by the subsequent finding that RecBCD acting in vitro under certain
      conditions did deliver a nick at chi. This widely embraced model has been
      challenged by a model in which the exonuclease activity of RecBCD destroys DNA
      from the enzyme's entry site to chi. The role of chi according to the new model
      is to inhibit this nuclease activity of RecBCD, perhaps by ejecting the RecD
      subunit from the enzyme, thereby revealing the enzyme's recombinase activity.

PMID- 7560869
TI  - Is the synaptonemal complex a disjunction machine?
AB  - The chiasma has been recognized as a major feature of meiosis both visually and
      functionally for > 85 years. But its functional basis remains poorly understood.
      In interaction with the spindle, it generally mediates the ultimate distribution
      of homologues to opposite poles at meiosis I to yield correct disjunction. Its
      establishment depends upon the presence of a completed reciprocal recombination
      (crossover) event, but its maintenance from the time of crossover completion
      until anaphase I (a period of substantial extent) requires additional functions.
      Evidence for the nature of these functions, their relationship to synapsis and
      conjectures on their place in the evolution of meiosis are discussed here.

PMID- 7560870
TI  - Mapping information roadways from sequence to phenotype and across species.
AB  - Expressing genetic concepts in ways that allow computerization of detailed
      genetic information and connectivitity with molecular biology databases is
      discussed. Interconnections between and among organismal and molecular databases
      are illustrated with examples from E. coli and maize databases on the World Wide
      Web connecting with GenBank, SwissProt, and other databases. Issues in
      development, maintenance, and widespread public use of such information are
      discussed.

PMID- 7560871
TI  - A complex alloantigen system in Florida sandhill cranes, Grus canadensis
      pratensis: evidence for the major histocompatibility (B) system.
AB  - The B blood group system constitutes the major histocompatibility complex (Mhc)
      in birds. The Mhc is a cluster of genes largely devoted to the processing and
      presentation of antigen. The Mhc is highly polymorphic in many species and, thus,
      useful in the evaluation of genetic diversity for fitness traits within
      populations of a variety of animals. Correlations found between particular Mhc
      haplotypes and resistance to certain diseases emphasize the importance of
      understanding the functional significance of diversity of the Mhc, particularly
      in species threatened with extinction. As part of studies focused on genetic
      diversity in wild birds, serological techniques were used to define a highly
      polymorphic alloantigen system in seven families of Florida sandhill cranes (Grus
      canadensis pratensis). The results of analyses with antisera produced within the
      crane families and with chicken Mhc antigen-specific reagents revealed a single
      major alloantigen system that is likely the Mhc of the Florida sandhill crane.
      Preliminary experiments indicate that these crane alloantisera will provide a
      means of defining the Mhc in other species of cranes.

PMID- 7560872
TI  - Mariner transposase-like sequences from the Hessian fly, Mayetiola destructor.
AB  - Transposable genetic elements are assumed to be a feature of all eukaryotic
      genomes. They can serve as vectors in gene transfer systems and as mutagenic
      agents for isolation of genes. Until recently their identification has been
      primarily limited to organisms subjected to extensive genetic or molecular study.
      The Hessian fly, Mayetiola destructor (Say), is an agriculturally important pest
      of wheat, Triticum aestivum L., in the United States and other parts of the
      world. We assessed the presence of mariner transposase-like sequences in M.
      destructor by polymerase chain reaction (PCR) assay designed to detect conserved
      regions of the mariner transposase gene. DNA sequence analysis of PCR products
      revealed sequences with similarities to putative mariner transposase gene
      subfamilies from Drosophila mauritiana and horn fly, Haematobia irritans. DNA gel
      blot analyses indicated sequences hybridizing to the mariner transposase-like PCR
      clones occur at a moderate to low copy number in M. destructor. Results suggest
      the presence of an endogenous mobile-element system in M. destructor, which might
      be developed into a gene transfer system or serve in mapping genes.

PMID- 7560874
TI  - Eye pigments in wild-type and eye-color mutant strains of the African malaria
      vector Anopheles gambiae.
AB  - Chromatographic analysis of pigments extracted from wild-type eyes of the
      mosquito Anopheles gambiae reveals the presence of the ommatin precursor 3
      hydroxykynurenine, its transamination derivative xanthurenic acid, and a dark,
      red-brown pigment spot that probably is composed of two or more low mobility
      xanthommatins. No colored or fluorescent pteridines are evident. Mosquitoes
      homozygous for an autosomal recessive mutation at the red-eye (r) locus have a
      brick-red eye color in larvae, pupae, and young adults, in contrast to the almost
      black color of the wild eye. Mosquitoes homozygous for this mutant allele have
      levels of ommochrome precursors that are indistinguishable from the wild-type,
      but the low-mobility xanthommatin spot is ochre-brown in color rather than red
      brown as in the wild-type. Mosquitoes with two different mutant alleles at the X
      linked pink-eye locus (p, which confers a pink eye color, and pw, which confers a
      white eye phenotype in homozygotes or hemizygous males) have normal levels of
      ommochrome precursors but no detectable xanthommatins. Mosquitoes homozygous for
      both the r and p mutant alleles have apricot-colored eyes and show no detectable
      xanthommatins. Both the pink-eye and red-eye mutations appear to involve defects
      in the transport into or assembly of pigments in the membrane-bound pigment
      granules rather then defects in ommochrome synthesis.

PMID- 7560873
TI  - Sry-negative XX sex reversal in the German shorthaired pointer dog.
AB  - Present hypotheses indicate that a testis differentiation cascade in mammals is
      induced by Sry, a gene encoding a DNA binding protein of the high mobility group
      (HMG) class. In XX sex reversal, individuals lacking a Y chromosome develop
      testicular tissue. Sry translocation from the Y to the X chromosome has been
      found in some, but not all, of these individuals. XX sex reversal in the German
      shorthaired pointer dog may be a model of Sry-negative XX sex reversal in humans.
      The purposes of this study were to report the familial occurrence of sex reversal
      and determine whether the conserved Sry HMG box, the region of the Sry protein
      essential for testis induction, is present in genomic DNA of affected dogs.
      Canine Sry HMG box sequences were used as primers in polymerase chain reactions.
      A 104 bp Sry HMG box product was generated from normal males, but not from
      females or XX sex reversed dogs. Parallel control reactions using hypoxanthine
      phosphoribosyl transferase primers generated a 177 bp product from all dogs. The
      pedigree of affected dogs and the absence of Sry HMG box sequences in their
      genomic DNA suggest that this disorder is due to a mutant autosomal gene in the
      testis differentiation cascade.

PMID- 7560875
TI  - Brown coat color in Icelandic cattle produced by the loci Extension and Agouti.
AB  - Inheritance of the colors black, brown, and red in Icelandic cattle was studied.
      The three colors are produced by two loci, Extension (E) and Agouti (A), with
      three alleles at the E locus: E(d) for dominant black; E+, intermediate, which
      allows expression of A locus alleles; and e for recessive red color. Two alleles
      are postulated at the A locus: A+, producing brown, and a, producing recessive
      black (nonagouti) when homozygous in E+/- animals. The dominant and recessive
      types of black are indistinguishable from each other phenotypically. The A
      alleles are only able to express their effect in E+/- genotypes. The E and A loci
      in cattle are postulated to be homologous to the E and A loci in the mouse.

PMID- 7560876
TI  - Clonal stability and mutation in the self-fertilizing hermaphroditic fish,
      Rivulus marmoratus.
AB  - Previous investigations of natural populations of the hermaphroditic, self
      fertilizing fish species Rivulus marmoratus demonstrated a surprising amount of
      interclonal differentiation among highly polymorphic "DNA fingerprint" loci. The
      genetic differentiation observed among clones was thought to be the effect of
      extreme population mixing because of high rates of migration and population
      extinction. It was demonstrated that mutation rates at hypervariable loci would
      have to exceed 10(-4) on average to alone account for the observed interclonal
      differences. The present study reports that, among laboratory lines of this
      species, mutation rates at the most unstable set of hypervariable loci are not
      greater than 3.52 x 10(-4), and are probably lower. Mutation rates at several
      other sets of loci are even lower. A field transplantation study demonstrated
      complete clonal stability over several generations. These results suggest that
      the high interclonal differences observed in natural populations of this species
      is not caused by a generally higher rate of mutation at these specific loci.

PMID- 7560877
TI  - HAPLO: a program using the EM algorithm to estimate the frequencies of multi-site
      haplotypes.

PMID- 7560878
TI  - Saponin pre-treatment in pre-embedding electron microscopic in situ hybridization
      for detection of specific RNA sequences in cultured cells: a methodological
      study.
AB  - We describe a method for detection of specific RNA targets in cultured cells at
      the electron microscopic (EM) level using pre-embedding in situ hybridization
      (ISH). The specimens were monitored by reflection-contrast microscopy (RCM)
      before processing for EM. A good balance between preservation of ultrastructure
      and intensity of hybridization signals was obtained by using mild aldehyde
      fixation followed by saponin permeabilization. Digoxigenin-labeled probes were
      used for detection of human elongation factor (HEF) mRNA in HeLa cells, immediate
      early (IE) mRNA in rat 9G cells, and 28S rRNA in both cell lines. The hybrids
      were detected immunocytochemically by the peroxidase/diaminobenzidine (DAB)
      method or by ultra-small gold with silver enhancement. Comparison of these
      methods favored the peroxidase/DAB system. The accessibility of RNA in the
      different cell compartments was dependent on the extent of cross-linking during
      primary fixation even after permeabilization with saponin. By using the most
      optimal ISH protocol and the peroxidase/DAB system, we detected 28S rRNA over all
      ribosomes in the cytoplasm but not in the nucleoli, and IE mRNA in a large spot
      with many smaller spots around it in the nucleoplasm as well as in speckles over
      the cytoplasm. The sensitivity of the method is such that HEF housekeeping gene
      transcripts were detected in the cytoplasm.

PMID- 7560879
TI  - Paraformaldehyde fixation of neutrophils for immunolabeling of granule antigens
      in cryoultrasections.
AB  - Paraformaldehyde (PFA) fixation was optimized to facilitate the immobilization
      and labeling of multiple granule antigens, using short fixation regimens and
      cryoultramicrotomy of unembedded neutrophils (PMNs). In the optimal protocol,
      extraction of azurophil granule antigens (especially of the abundant elastase)
      was obviated by manipulating the polymeric state of PFA, and hence its rate of
      cross-linking, by altering its concentration and pH in a multistep process.
      Primary fixation conditions used (4% PFA, pH 8.0, 5 min) favor fixative
      penetration and rapid cross-linking. Stable cross-linking of the antigen was
      achieved in a secondary fixation step using conditions that favor larger, more
      cross-linking polymeric forms of PFA (8% PFA, pH 7.2, 15 min). Immobilization of
      granule antigens was enhanced by flotation of cut sections on fixative (8% PFA,
      pH 8.0) before labeling and by using post-labeling fixation with 1%
      glutaraldehyde. The optimized protocol facilitated immobilization and
      immunolabeling of elastase, myeloperoxidase, lactoferrin, and cathepsin D in
      highly hydrated, unembedded PMNs.

PMID- 7560880
TI  - Image analysis and image processing as tools to measure initial rates of enzyme
      reactions in sections: distribution patterns of glutamate dehydrogenase activity
      in rat liver lobules.
AB  - To analyze regional differences in the activity of glutamate dehydrogenase in rat
      liver in situ, we developed an image recording and processing system for
      monitoring the formation of a colored final reaction product in time. All
      absorbance measurements of test and control reactions in time in consecutive
      sections were used to fit the data to a quadratic curve, with the derivative at t
      = 0 representing the initial velocity of formazan formation. The images of
      sections incubated for test and control reactions were topographically matched
      with an affine transformation using the positions of vessels as fiducials.
      Specific enzyme activity was calculated by subtracting the coefficients
      representing the initial velocity at corresponding locations in the test and
      control reactions and appeared to be 8 and 4 mumoles glutamate converted per min
      per cm3 of tissue at 20 degrees C in pericentral and periportal zones of fasted
      female rats, respectively. Those values are in agreement with biochemical data.
      The ability to construct two-dimensional images of cellular distribution patterns
      of enzyme activity in liver lobules is particularly useful for the study of
      metabolic zonation in this organ.

PMID- 7560881
TI  - Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in
      human and mouse development.
AB  - Osteogenic protein-1 (OP-1; BMP-7) is a member of the bone morphogenetic protein
      subfamily. Because members of the TGF-beta superfamily have a role in tissue
      development, the distribution of OP-1 expression in developing human embryos (5-8
      gestational weeks) and fetuses (8-14 gestational weeks) and mouse (9.5-17.5
      gestational days) fetuses was examined. Northern hybridization with specific OP-1
      probes revealed two mRNA species of 4 and 2.2 KB. Highest levels of OP-1 mRNA
      were found in human fetal kidney and heart between 12-14 weeks of gestation. By
      in situ hybridization, the OP-1 transcripts were found in various tissues, i.e.,
      the ectodermal epithelium of the mouse fore- and hindlimbs, heart, teeth,
      intestinal epithelium, perichondrium, hypertrophic chondrocytes, and
      periosteum/osteoblast layer of developing human bones. In kidneys, transcripts
      were first detected in the epithelium of the branching uretheric buds, whereas at
      later stages glomeruli were the major site of OP-1 mRNA accumulation. These data
      suggest that, although OP-1 has been isolated from bone matrix, it may have
      additional regulatory roles in the morphogenesis and/or function of the kidney,
      limb bud, tooth, heart, and intestine.

PMID- 7560882
TI  - A new histochemical method for detection of sialic acids using a physical
      development procedure.
AB  - We have established an efficient histochemical method for demonstration of sialic
      acids in light microscopy. The method consists of a selective periodate oxidation
      phenylhydrazine blockade and a thiocarbohydrazide-silver protein sequence
      followed by a physical development procedure. From the results obtained by the
      present experimental and control studies in tissue sections from a series of rat
      and mouse organs, such as stomach, duodenum, colon, liver, sublingual gland,
      lung, and kidney, the specificity and sensitivity of the method were sufficient.
      In the tissues tested, sialic acids were visualized as distinct brownish and
      blackish reaction products. Comparisons of the new method with the periodic acid
      phenylhydrazine-Schiff (PA-P-S) or selective periodate oxidation-Schiff (PA*-S)
      method employed hitherto have confirmed that the new method reported here is
      higher in efficiency and visibility of reaction products than the latter two
      methods.

PMID- 7560883
TI  - Localization of NADPH diaphorase in the mouse uterus during the first half of
      pregnancy and during an artificially induced decidual cell reaction.
AB  - Uteri from non-pregnant and pregnant (Days 1-10) mice were examined for the
      presence of NADPH diaphorase (NADPH-d) activity by histochemical techniques.
      Macrophages positive for NADPH-d were observed in all uterine sections but
      appeared to migrate out of the implantation site and cluster in the mesometrium
      and interimplantation zones beginning on Day 4. NADPH-d activity was seen in the
      luminal and glandular epithelium and in several isolated fibers coursing through
      the myometrium. Many branches of the uterine artery also expressed activity, with
      the most intense staining in the vessels of the mesometrium. However, the most
      remarkable staining began on Day 6 within the primary decidual zone. When the
      stromal cells underwent decidualization, they began to show NADPH-d activity,
      with the pattern of activity matching the expanding area of decidualization. By
      Day 9 most of the decidual cell reaction had occurred and the mesometrial
      decidual staining began to decrease. However, the blood vessels and the cells
      surrounding the developing blood spaces continued to express activity, and heavy
      staining was evident within the antimesometrial decidua. No NADPH-d activity was
      seen in any of the trophoblast cells at any time, or in embryonic tissue, except
      on Day 8. NADPH-d has been used to identify nitric oxide (NO) synthase.
      Therefore, it may represent an NO-mediated paracrine control over decidual blood
      flow, myometrial quiescence, or immune response during pregnancy.

PMID- 7560884
TI  - Changes in integrin expression during chondrogenesis in vitro: an
      immunomorphological study.
AB  - Integrins are receptors composed of ligand-specific alpha-chains and cell type
      specific beta-chains which are involved in cell-cell and cell-matrix
      interactions. The distribution of alpha 1- and alpha 3-integrins as well as
      collagen Types I and II, was investigated by immunofluorescence and
      immunoelectron microscopy during chondrogenesis in organ culture after various
      culture periods. Mesenchymal cells from limb buds of Day 12 mouse embryos were
      grown at high density. Within the first 2 days of the culture period, only alpha
      1-integrin could be detected. Formation of cartilage-specific matrix on Day 3 was
      accompanied by the occurrence of alpha 3-integrin. On Day 7, alpha 3 was present
      only in cartilage nodules, whereas alpha 1 was strongly expressed in the
      perichondrium and was more or less homogeneously distributed in the surrounding
      mesenchyme. On Day 14, alpha 1-integrin was again detectable in cartilage. We
      suggest that the change in collagen formation from Type I to Type II during
      chondrogenesis is accompanied by a change in integrin expression from alpha 1 to
      alpha 3. Conversely, dedifferentiation of chondrocytes in aging cartilage is
      accompanied by the occurrence of collagen Type I and alpha 1-integrin. Therefore,
      a strict correlation between the collagen type synthesized by the cells and the
      appropriate receptor presented by the cells is suggested.

PMID- 7560886
TI  - A simple technique for staining of cell membranes with imidazole and osmium
      tetroxide.
AB  - We describe a simple new technique based on the affinity of imidazole and osmium
      tetroxide for unsaturated lipids. Organs (e.g., kidney, liver, intestine) were
      perfused in vivo with a glutaraldehyde solution. Tissue fragments were then
      immersed in a solution containing imidazole and OsO4 and are further stained with
      a double lead and copper citrate solution. Ultra-thin (0.06 microns) or thick
      (0.1-0.3 microns) sections were observed with transmission electron microscopy
      (80-100 kV). The method presented permits excellent visualization of cell
      membranes (e.g., endoplasmic reticulum, endocytotic apparatus) because it favors
      good resin penetration and the alkaline pH preserves cell volume. A better
      stereomicroscopic analysis of the relationship between cell organelles can be
      carried out with thick sections. The imidazole/osmium can be used routinely
      because the technical steps are easy and simple to follow. Furthermore, it can
      complement other cytochemical methods.

PMID- 7560885
TI  - Evidence of foam cell and cholesterol crystal formation in macrophages incubated
      with oxidized LDL by fluorescence and electron microscopy.
AB  - Macrophage-derived foam cells are a prominent component of developing
      atherosclerotic lesions. We describe an in vitro model of foam cell formation
      which mimics some aspects of the evolution of foam cells in mature
      atherosclerotic lesions. Thioglycollate-elicited mouse peritoneal macrophages
      were incubated with copper-oxidized LDL (ox-LDL) for periods up to 168 hr.
      Identifiable foam cells were present after incubation with ox-LDL at 24, 72, and
      168 hr. Control cells incubated without ox-LDL did not form foam cells.
      Fluorescence microscopy after staining with Nile red exhibited progressive
      accumulation of lipids, and transmission electron microscopy (TEM) showed
      distinct ultrastructural changes over time. Macrophages at 24 hr had a few non
      membrane-bound lipid droplets but were otherwise identical to control cells.
      These lipid droplets fluoresced yellow-gold after Nile red staining. After 72 hr
      of incubation with ox-LDL, in addition to increased numbers of non-membrane-bound
      lipid inclusions, macrophages contained membrane-bound multilamellar lipoid
      structures. These multilamellar structures corresponded to areas of reddish
      orange fluorescence after Nile red staining. In macrophages incubated with ox-LDL
      for 168 hr, the amount of cellular lipid was further increased and cholesterol
      crystal profiles were apparent within some multilamellar lipoid structures.
      Biochemical analysis showed that the total cholesterol content steadily increased
      over 168 hr. The increase in total cholesterol was accompanied by a dramatic
      increase in free cholesterol between 72 and 168 hr. These results demonstrate
      that long-term incubation of macrophages with ox-LDL increased lipid deposition
      in cultured cells and that, under the conditions studied, cholesterol crystals
      formed in macrophage foam cells. Moreover, this system allows investigation of
      the evolution of foam cells showing some characteristics of those found in
      atherosclerotic lesions.

PMID- 7560887
TI  - Ultrastructural localization of collagen types II, IX, and XI in the growth plate
      of human rib and fetal bovine epiphyseal cartilage: type XI collagen is
      restricted to thin fibrils.
AB  - The collagen fibrils of hyaline cartilage vary in diameter depending on
      developmental stage and location within the tissue. In general, growth plates and
      fetal epiphyseal cartilages contain fibrils with diameters of less than
      approximately 25 nm, whereas the permanent cartilage of adult tissues contains
      fibrils of approximately 30-200 nm. The interstitial collagen fibrils of fetal
      cartilage are complex, having at least three collagen types as integral
      components. Type XI, a member of the fibrillar collagen class, has been proposed
      to limit fibril diameter. To test this proposition we sought to determine if Type
      XI collagen was preferentially associated with fibrils of smaller diameter. We
      focused our study on human juvenile rib growth plate, which has thin fibrils in
      the hypertrophic zone, thick fibrils in the resting zone or permanent cartilage,
      and a mixture of thin and thick fibrils in the proliferative zone. Tissues were
      examined by immunoelectron microscopy with antipeptide antibodies to the carboxyl
      telopeptide and to the amino terminal non-triple-helical domains of alpha 1 (XI).
      These studies showed that (a) both epitopes of Type XI collagen were readily
      accessible to antibodies at the fibrillar surface, (b) Type XI collagen was
      associated predominantly with fibrils < 25 nm in diameter, (c) Type XI collagen
      was not found in thick fibrils even after disruption with chaotropic agents, and
      (d) collagen Types II and IX were associated with fibrils of all sizes. These
      studies were extended to human newborn epiphyseal cartilage and to fetal calf
      cartilage, with the same result.

PMID- 7560888
TI  - Ultrastructural localization of Na,K-ATPase in the gerbil cochlea.
AB  - The transport enzyme Na,K-ATPase has been localized to several different cell
      types within the inner ear by enzyme cytochemistry, immunohistochemistry, and in
      situ hybridization. Although these histochemical procedures have provided a
      fairly consistent pattern of the enzyme's distribution, the precise location of
      Na,K-ATPase in the cell membrane of some polarized and non-polarized cell types
      remains uncertain. We addressed this problem in the gerbil cochlea using electron
      microscopic immunogold cytochemistry. The results confirmed prior ultrastructural
      localization of Na,K-ATPase along the basolateral plasma membrane of strial
      marginal and outer sulcus epithelial cells but differed from a previous report in
      failing to detect the enzyme at the surface of strial intermediate cells. The
      findings also concurred with and extended previous work in showing immunogold
      labeling along the entire cell membrane of non-polarized Type II fibrocytes in
      the inferior portion of the spiral ligament and of subpopulations of fibrocytes
      in the suprastrial and supralimbal regions. Our observations agreed further with
      light microscopic immunostaining in displaying uniform gold labeling for Na,K
      ATPase in the neurilemma of Type I spiral ganglion neurons, even though these
      cells are completely ensheathed by myelin. Surprisingly, the enzyme was
      detectable in the neurilemma of afferent but not that of efferent nerve processes
      beneath hair cells.

PMID- 7560889
TI  - Quantitative and three-dimensional analysis of human Langerhans cells in
      epidermal sheets and vertical skin sections.
AB  - We used confocal laser scanning microscopy to analyze and compare Langerhans
      cells (LCs) in normal skin of six subjects. Acetone-fixed epidermal sheets and 25
      microns vertical skin sections were incubated with fluorescein isothiocyanate
      conjugated mouse monoclonal antibodies directed against HLA-DR. An individual
      threshold setting algorithm compensating for the differences in background
      fluorescence was applied to identify specific fluorescence. No statistically
      significant difference was found in the relative volume of epidermal HLA-DR
      reactivity between epidermal sheets (14 +/- 5%) and vertical skin sections (13 +/
      6%) or in the number of dendrites per HLA-DR+ LCs (7.8 +/- 3.1 and 5.9 +/- 3.1,
      n = 58, respectively). However, statistically significant higher background
      intensity was found in vertical sections than in epidermal sheets. Three
      dimensional (3D) reconstructions of HLA-DR+ LCs revealed a concentration of HLA
      DR to one or a few intracellular vesicles in 42 of 58 analyzed LCs in epidermal
      sheets and in 18 of 58 analyzed LCs in vertical sections. Direct contact between
      dendrites from different LCs was not found. The results indicate that both skin
      forms are suitable for quantitative studies. Owing to less background intensity
      and larger tissue volume, detailed 3D analysis of LCs is preferably performed on
      epidermal sheets rather than on vertical sections.

PMID- 7560890
TI  - Detection of P53 expression and S-phase cell fraction in paraffin-embedded tissue
      by a double-labeling technique.
AB  - TP53 is a gene that normally regulates cell growth and division. Alterations to
      it may induce a proliferative advantage and confer an aggressive phenotype. In
      breast cancer, we observed a poor correlation (rs = 0.17) between P53 expression
      and proliferative activity evaluated as [3H]-thymidine ([3H]-dT) labeling index
      and an independent prognostic relevance of the two variables. We used a double
      labeling technique to simultaneously evaluate the fraction of P53-positive and
      [3H]-dT-labeled cells to analyze the degree of association between the two
      markers on individual cells in order to understand their biological significance.
      The study was performed on a series of 44 P53-positive (P53+) breast cancers.
      Histological sections were immunostained for P53 with monoclonal antibody (MAb)
      PAb1801 and then processed for autoradiography. A weak direct relation between
      P53 positivity and [3H]-dT incorporation (rs = 0.4) was observed on the overall
      series of P53+ tumors and was maintained in subgroups defined by several
      biological and pathological features, except for estrogen receptor-negative
      tumors. The simultaneous presence of P53 expression and [3H]-dT incorporation was
      directly and significantly proportional to the fraction of S-phase cells of the
      tumor (rs = 0.7). Conversely, the fraction of cells expressing only P53 was
      inversely related to cell proliferation (rs = -0.66). These findings support the
      hypothesis that P53 has biological functions other than cell cycle regulation.

PMID- 7560891
TI  - Immunogold localization of beta 1-integrin in bone: effect of glucocorticoids and
      insulin-like growth factor I on integrins and osteocyte formation.
AB  - Insulin-like growth factor I (IGF-I) and high-dose glucocorticoids exert opposite
      effects on bone formation. Because integrins are involved in cell and matrix
      organization, the effect of glucocorticoids and IGF-I on integrins was
      investigated in bone. An immunogold transmission electron microscopic (TEM)
      method was developed and applied to an organ culture system of 20-day fetal rat
      parietal bones, which mineralize in vitro. In parietal bone culture, 100 mM
      corticosterone treatment for 72 hr decreased calcification by 29%, disrupted
      osteoblast organization, and decreased the number of osteocytes. The quantity of
      osteoblast processes and the number of osteocytes per unit bone area were
      decreased by 48% and 56%, respectively. This effect was dose-dependent. The beta
      1-integrin subunit was localized equally to apical and basal osteoblast surfaces
      by immunogold TEM. Compared to untreated control cultures, corticosterone (100
      nM) decreased beta 1 by one third. In contrast, treatment with IGF-I for 72 hr
      increased calcification by 38%, cell processes by 71%, and osteocytes per unit
      area of bone by 107%. The number of gold particles localizing beta 1 on the
      osteoblast plasma membrane doubled, almost entirely on the apical surface of the
      osteoblast. Glucocorticoids and IGF-I had no significant effect on beta 1 levels
      in osteocytes. In conclusion, glucocorticoids and IGF-I modulate integrin levels
      on osteoblasts, and influence osteocyte formation and bone calcification.
      However, neither glucocorticoids nor IGF-I alter beta 1-integrin levels on
      osteocytes.

PMID- 7560893
TI  - Patterns of immunoreactivity to an anti-fibronectin polyclonal antibody in
      formalin-fixed, paraffin-embedded oral tissues are dependent on methods of
      antigen retrieval.
AB  - The influence of antigen retrieval (AR) technique on immunoreactivity in formalin
      fixed, paraffin-embedded tissues is recognized. In focal reactive overgrowths of
      oral mucosa, we noted that patterns of immunoreactivity to a fibronectin
      polyclonal antibody were dependent on methods of AR. To establish these patterns
      we investigated eight pyogenic granulomas and eight fibroepithelial polyps. In
      the absence of AR no immunoreactivity was observed. After alpha-chymotrypsin AR a
      band of intense immunoreactivity was associated with vascular endothelial cells,
      with either minimal or no staining of connective tissue. After microwave AR
      immunoreactivity was observed in connective tissue, especially in the
      subepithelial region, but there was no specific vascular staining. After
      autoclave AR immunoreactivity was observed in connective tissue and also in
      epithelial nuclei. To determine if these results represented either changes
      induced by tissue fixation and processing or exposure of epitopes normally masked
      in vivo, we investigated frozen sections from two fibroepithelial polyps and one
      pyogenic granuloma. In frozen sections immunoreactivity was observed around
      vascular endothelial cells and within connective tissue, especially in the
      subepithelial region, but not in epithelia. This study provides indirect evidence
      that alpha-chymotrypsin and heat-mediated AR protocols expose different masked
      epitopes, and reinforces the need to undertake appropriate pilot studies for
      immunohistochemical investigation of archival tissue.

PMID- 7560892
TI  - Co-expression of vimentin and 19S-thyroglobulin in follicular cells located in
      the C-cell complex of dog thyroid gland.
AB  - The localization of vimentin, an intermediate filament protein, in the dog
      thyroid cells was examined by immunohistochemistry with a monoclonal antibody
      against vimentin and polyclonal anti-19S-thyroglobulin and anti-calcitonin
      antibodies. In the dog thyroid gland, C-cells are usually distributed as large
      cell groups in an interfollicular location. In addition, C-cell complexes that
      are special C-cell clusters associated with other epithelial elements and cysts
      are frequently located around the parathyroid gland IV. The C-cell complexes are
      remnants of embryonic ultimobranchial bodies and retain fetal characteristics for
      long periods. Follicular cells in various stages of differentiation are observed
      in the C-cell complexes and large C-cell groups of postnatal dogs: (a) cell
      masses not yet organized into follicles, (b) primitive and small follicles
      storing colloid, and (c) small follicles without colloid storage. The immature
      follicular cells in the C-cell complexes and large C-cell groups express
      immunoreactivity for vimentin in addition to 19S-thyroglobulin. When the
      follicular cells stored considerable amounts of colloid in the follicular lumina,
      vimentin immunoreactivity disappeared from them. Typical thyroid follicles showed
      no immunoreactivity for vimentin. In dog fetuses in which follicular cells were
      arranged in cell clusters or were vigorously forming follicles, no
      immunoreactivity for vimentin was observed in the thyroid parenchyma. These
      results indicate that vimentin is specifically expressed in the immature
      follicular cells derived from the ultimobranchial anlage. The vimentin filaments
      may participate in increased cellular activities in the cells, i.e.,
      thyroglobulin synthesis and folliculogenesis.

PMID- 7560894
TI  - Elastic lamina growth in the developing mouse aorta.
AB  - The growth and development of elastic laminae in the mouse aortic media were
      investigated by light and electron microscopic autoradiography after a single SC
      injection of L-[3,4-3H]-valine. Because of the remarkable stability of elastin,
      radiolabel incorporated into the elastic laminae during early stages of aortic
      development can be identified in the mature vessel. Light microscopic
      autoradiographs of aortae from mice injected with radiolabeled valine at 3, 14,
      or 21 days of postnatal age and sacrificed at 4 months of age showed silver
      grains evenly distributed around the circumference of the vessel, suggesting
      uniform elastic lamina growth. Electron microscopic autoradiographs of aortae
      from mice injected at 3 and 14 days' postnatal age and killed at 4 months of age
      showed the elastin initially deposited at 3 days to be in the center of the
      lamina, whereas the elastin deposited at 14 days remained peripherally located.
      These observations suggest that elastin deposited early in development does not
      undergo any significant redistribution during growth of the vessel. Because the
      aorta continues to increase in diameter after the elastic laminae are essentially
      complete, the fenestrations in the laminae were investigated as possible sites of
      further expansion of the laminae. In aortae from mice injected at 3 days and
      sacrificed at 4 days of postnatal age, the edges of the elastic lamina that
      border on fenestrations showed a large number of silver grains. Regions of the
      elastic lamina at some distance from the fenestration, however, appeared to be
      associated with fewer grains. Results from this study not only present unique
      observations of elastin deposition in developing elastic laminae but also provide
      evidence that the fenestrations in the elastic laminae may play a role in their
      continued expansion during later stages of aortic development.

PMID- 7560895
TI  - Immunohistological detection of gap junctions in human lymphoid tissue:
      connexin43 in follicular dendritic and lymphoendothelial cells.
AB  - We investigated the expression of gap junction connexins26, -32, and -43 in
      normal, reactive, and diseased human lymphoid tissue with single and double
      immunolabeling and confocal laser scanning microscopy. In all tissues, connexin43
      positivity was detected in follicular dendritic cells positive for CD21 and CD35
      antigens, around lymphoendothelial cells moderately positive for Factor VIII,
      CD31 and cathepsin-D antigens; and somewhat in vascular endothelia including high
      endothelial venules strongly positive for Factor VIII and CD31 antigens. The
      ultrastructural hallmark of gap junctions, pentalaminar structures with
      appropriate spacing, was found in follicular dendritic cell processes. Connexin43
      was also detected between smooth muscle and stromal cells of the gut, in capsular
      fibroblasts, and in tonsil epithelium. Neither connexin32 nor -26 was revealed,
      except for connexin26 in the tonsil epithelium. In follicular dendritic cells,
      connexin43 co-localized closely with the desmosomal proteins desmoplakin and
      desmoglein, suggesting that cell adherence has a role in gap junction formation.
      Most connexin43 was observed in sinus lining cells of lymph nodes involved in
      malignancies and in follicular dendritic cells in the light zone of germinal
      centers where maturing but still proliferating lymphocytes are situated. In the
      light of their distribution, gap junctions may play a part in regulating the
      growth of germinal centers and in integrating activating or controlling signals
      in follicular dendritic and sinus lining cell networks. Because connexin43 is the
      connexin of stromal cells, finding it in follicular dendritic cells in consistent
      with the proposal that these cells originate from resident stromal cells.

PMID- 7560896
TI  - Demonstration of tryptase in bovine cutaneous and tumor mast cells.
AB  - We examined three tissue samples from each of four cows with non-lesional skin,
      tissue samples from a cow with multiple cutaneous mast cell tumors, and samples
      from another cow in which mast cells were infiltrating multiple lymphosarcomas of
      the skin, for the presence of tryptase and chymase by enzyme cytochemical and
      immunohistological methods. The enzyme activities of tryptase and chymase were
      tested using N-carbobenzoxy-glycilglycil-L-arginine-2-naphthylamide (Z-Gly-Gly
      Arg-NA) and naphthol-AS-D-chloroacetate (N-AS-D-CA) as substrates, respectively.
      Tryptase reactivity could be demonstrated in frozen and Carnoy-fixed paraffin
      sections. Chymase reactivity was seen in neither frozen nor paraffin sections of
      formalin- or Carnoy-fixed skin tissues. Antibody linkage with a polyclonal rabbit
      anti-human skin tryptase antibody was highly specific in bovine normal cutaneous,
      infiltrating, and tumor mast cells. More than 90% of the tumor mast cells were
      distinctly tryptase-positive. With alcian blue, only slightly more than 10% of
      the mast cells stained clearly positive and with methylene blue hardly any
      staining of mast cell granules could be demonstrated. No antibody labeling of
      mast cell granules in any of the tissue sections was detected by the use of
      rabbit anti-dog chymase antiserum. These results indicate that there is a
      striking antigenic similarity of bovine tryptase to its canine and human
      equivalents. The demonstration of tryptase is an important tool in confirming the
      diagnosis of undifferentiated mast cell tumors. In contrast to other species,
      chymase appears to be completely absent in bovine skin mast cells.

PMID- 7560897
TI  - Immunocytochemical study of the degradation of elastic fibers in a living
      extracellular matrix.
AB  - We used ultrastructural and immunocytochemical technique to follow the movement
      of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) through
      a living extracellular matrix produced by cultured smooth muscle cells and to
      compare the effect of the two elastases on elastic fibers in situ. Although both
      enzymes solubilize elastin purified from these cultures at similar rates, PPE
      solubilized 11.5 times more elastin from the intact cultures than did HNE. The
      difference in the rate of elastin solubilization from the cultures parallels the
      degree of elastic fiber degradation and the emphysema-inducing potency of the two
      elastases when they are instilled into animal lungs. Immunohistochemical studies
      employing antibodies to HNE and PPE revealed that PPE penetrates the smooth
      muscle cell cultures more readily than does HNE. Because the amount of elastin in
      these cultures increases with increasing distance from the free surface, the
      lesser amounts of elastin solubilized by HNE may be partly due to poor
      penetration of HNE into the living extracellular matrix, resulting in limited
      access to elastin substrate. Ultrastructural and immunocytochemical studies
      indicated, however, that even when HNE does have access to elastin substrate, it
      is less efficient than PPE at penetrating and degrading individual elastic
      fibers.

PMID- 7560898
TI  - In situ substrate specificity and ultrastructural localization of polyamine
      oxidase activity in unfixed rat tissues.
AB  - Data concerning the substrate specificity and the exact intracellular
      localization of the polyamine-catabolizing enzyme polyamine oxidase are
      conflicting. Biochemical studies have shown that N1-acetylation of spermine and
      spermidine dramatically increases the specificity of these compounds for
      peroxisomal polyamine oxidase to produce spermidine and putrescine, respectively.
      On the other hand, polyamine oxidase activity was demonstrated histochemically
      both in peroxisomes and in cytoplasm of several tissues, using spermidine and/or
      spermine as substrate. To elucidate the in situ substrate specificity of
      polyamine oxidase and the localization of its activity, enzyme activity was
      detected in rat liver, kidney, and duodenum at the light and electron microscopic
      levels. For this purpose, unfixed cryostat sections were applied to avoid changes
      in enzyme activity owing to chemical fixation. Spermine, spermidine, their N1
      acetylated forms, and putrescine were used as substrates, and cerium ions as
      capturing agent for H2O2. Control reactions were performed in the absence of
      substrate or in the presence of substrate and specific oxidase inhibitors. At the
      light microscopic level, final reaction product specifically generated by
      polyamine oxidase activity was found exclusively in a granular form in
      hepatocytes, epithelial cells of proximal tubules of the kidney, and epithelial
      cells of duodenal villi with N1-acetylspermidine or N1-acetylspermine as
      substrates. Final reaction product was not observed in any of the tissues after
      incubation in the presence of putrescine, spermidine, or spermine. Formation of
      specific final reaction product was prevented by incubation in the presence of a
      specific polyamine oxidase inhibitor, but it was not affected by a diamine
      oxidase inhibitor. Ultrastructural studies revealed that polyamine oxidase
      activity is localized exclusively to the matrix of peroxisomes of kidney and
      liver and to microperoxisomes of the duodenum. The localization patterns obtained
      with unfixed tissues are in agreement with biochemical data. Strong
      intraperoxisomal, interperoxisomal, and intercellular heterogeneity in polyamine
      oxidase activity was found in all tissues investigated.

PMID- 7560899
TI  - Microwave-enhanced in situ end-labeling of fragmented DNA: parametric studies in
      relation to postmortem delay and fixation of rat and human brain.
AB  - In situ end-labeling (ISEL) identifies DNA fragmentation in apoptotic or necrotic
      nuclei in tissue sections. However, application of ISEL on human brain requires
      conservation of DNA integrity during the postmortem delay (PMD) and good
      accessibility of fragmented DNA after (prolonged) tissue fixation. We therefore
      investigated ISEL in relation to PMD and fixation in rat and human brain.
      Application on a unilateral lesion model in perfused rat brain revealed that
      prolonged post-fixation strongly diminished ISEL results. However, microwave pre
      treatment can counteract these masking effects without inducing nonspecific
      labeling contralaterally. On the other hand, in briefly post-fixed, perfused
      brain or immersion-fixed rat and human PMD brain, microwave pre-treatment was
      deleterious and induced strong nonspecific labeling. In young rat brain, PMD did
      not influence the low numbers of apoptotic nuclei until 24 hr PMD, when massive
      nuclear labeling occurred. In human cortex, DNA fragmentation patterns were
      independent of duration of fixation or PMD and were already present from 4.25 hr
      PMD onwards. Our data suggest that ISEL on human brain represents antemortem DNA
      damage rather than PMD artifacts. Furthermore, microwave pre-treatment appears
      beneficial only in particular fixation conditions.

PMID- 7560900
TI  - Localization of transglutaminase in human lenses.
AB  - Transglutaminase activity has been detected in the lenses of laboratory animals
      and in human cataracts. However, its distribution in the lens tissue has not been
      investigated. Using a monoclonal antibody against tissue transglutaminase, we
      showed by Western blotting and immunoabsorption that transglutaminase of normal
      human lens is immunologically related to tissue transglutaminase but has a
      slightly higher M(r) than the latter enzyme. Using monoclonal or polyclonal
      antibody against tissue transglutaminase, lens transglutaminase was localized to
      the epithelial cell layer on the anterior lens surface and to a thin stripe
      between the capsule and the peripheral cortex on the posterior surface. Lens
      fibers were not stained with the antibodies. Factor XIII, another
      transglutaminase, could not be detected in the lens tissue. The localization of
      transglutaminase in the lens suggests that lens transglutaminase is synthesized
      in the epithelial cells and secreted into the virtual space between the capsule
      and the peripheral cortex spreading all around the lens substance.

PMID- 7560901
TI  - Use of double labeling and photo CD for morphometric analysis of injured skeletal
      muscle.
AB  - We used computer-assisted analysis of myofiber cross-sectional areas to measure
      skeletal muscle responses to injury and disease. We developed a simple,
      inexpensive method for measuring myofiber size in human muscle samples using
      Kodak photo compact discs (CDs) as the image source. The photo CD serves as a
      permanent image storage medium and provides a high-resolution image that can be
      used to detect small myofibers. The use of double labeling for dystrophin and
      desmin allowed positive identification of both degenerating and regenerating
      fibers in a single biopsy specimen.

PMID- 7560902
TI  - Effect of prolonged hyperventilation on ischemic injury of neurons after global
      brain ischemia in the dog.
AB  - The influence of prolonged postischemic hyperventilation was studied in the model
      of global brain ischemia produced by 15 min cardiac arrest in dogs with 8 h
      recirculation. Histopathological examination of neuronal damage using silver
      impregnation showed the presence of numerous heavy argyrophylic neurons in the
      striatum and CA2 hippocampal subfield after 8 h of normoxic reperfusion. In dogs
      with prolonged 8 h postischemic hyperventilation a reduction in the occurrence of
      argyrophylic neurons in the striatum and their significant decrease in the
      hippocampal area were found. Electron microscopic study was performed to
      characterize the effect of respiratory alkalosis on the ultrastructural changes
      in neurons and correlate them with the results of silver impregnation.
      Ultrastructural analysis after the cardiac arrest without recirculation did not
      reveal the presence of dark neurons within the striatal and hippocampal areas.
      Neuronal alterations included a decrease in endoplasmic reticulum, mitochondrial
      swelling and a mild chromatin clumping. After 8 h of normoxic reperfusion many
      dark, shrinked neurons containing perinuclear clusters of clear vesicles were
      found. In hyperventilated animals the occurrence of dark neurons with extensive
      perineuronal edema was substantially reduced in the CA2 subfield. The effect of
      hyperventilation on postischemic calcium overload is discussed.

PMID- 7560903
TI  - Visualization of Muller (retinal glial) cells by bulk filling with procion
      yellow.
AB  - A method is presented that allows for an easy and reliable demonstration of
      retinal glial (Muller) cell morphology. When a 3% solution of the fluorescent dye
      Procion Yellow (reactive yellow, Sigma) is placed on isolated living retinae for
      2 hrs, many Muller cells take up the dye. In paraffin sections, the cells can be
      observed by confocal microscopy in great detail. As the cells are filled
      throughout their length, the method has advantages over most immunocytochemical
      methods which label only parts of the cells. The method was applied to retinae of
      frogs, rats, guinea pigs, and rabbits. The vitread trunks of the cells differed
      in diameter. Those of frogs and rats were thin (less than 1 to 2 microns
      diameter) whereas those of guinea pigs and rabbits were thicker (2 to 5 microns).
      In all species studied the following rule was found. In thick central regions of
      the retina, Muller cells were long with slender trunks whereas in the thin
      retinal periphery, the Muller cells had thick short trunks. There was an inverse
      relationship between length and diameter of Muller cell trunks. Mammalian Muller
      cells were densely packed and had rather cylindrical endfeet. In the frog retina,
      Muller cells were more sparsely distributed, and the endfeet formed wide, flat
      funnels. It is concluded that the higher metabolic rate of mammalian retinae
      requires more densely packed Muller cells than occur in the amphibian retina.

PMID- 7560904
TI  - Postnatal development of NADPH-diaphorase/nitric oxide synthase positive nerve
      cells in the visual cortex of the rat.
AB  - The postnatal development of NADPH-diaphorase (NADPH-d)/nitric oxide synthase
      (NOS) positive nerve cells was studied in the visual cortex of rats on postnatal
      day 1, 5, 10, 15, 20, 30 and at the age of 1 year. NADPH-d was demonstrated
      enzymhistochemically and NOS immunohistochemically using a polyclonal antibody.
      NADPH-d is localized in nerve cell somata, dendrites, axons and blood vessels,
      whereas NOS immunoreactivity is only detectable in nerve cells. The identity of
      NADPH-d cells with those which contain NOS was proved in double labelling
      experiments in the cortex of rats on postnatal day 5, 15 and at the age of 1
      year. The results of these experiments have shown that in the cortex of rats
      NADPH-d positive cells are identical with NOS-positive cells in the different
      stages. Therefore we have used NADPH-d histochemistry in all other postnatal
      stages as a marker for neurons which contain NOS. NOS positive nerve cells appear
      very early on postnatal day 1 in the intermediate (white matter) and subplate
      (layers V and VI) region as small undifferentiated neurons. During the following
      postnatal differentiation these neurons reached their typical morphology in the
      second week and appeared in all layers. Neurons in layers V and VI preceded those
      in the superficial layers. Nerve cells in the white matter seem to have their own
      differentiation pattern because they showed characteristic features of
      immaturated varicose dendrites for a longer time. The investigation of soma size
      with the computerized "Kontron Videoplan" system (Zeiss, Germany) showed the
      largest cell bodies on postnatal day 20 which then decreased towards adulthood.
      Between postnatal day 10 and 20 some NOS-positive neurons especially in the deep
      layers displayed symptoms of degeneration, like shrunken cell bodies, corkscrew
      and twisted dendrites. Furthermore, NOS-positive neurons in layer I are not
      detectable in adult neocortex. These observations could suggest that some NOS
      positive cells in the cerebral cortex of rats may occur only transiently. Also in
      the neuropil some alterations in the localization of NOS positive axonal boutons
      were observed. On postnatal day 10 NOS negative cell somata were shadowy
      surrounded by boutons. During the further development from postnatal day 20 until
      adulthood this particular position was no longer visible. Beside the NOS cells
      which played a transient role, the majority of these cells survived to adulthood
      and are a morphological (Martinotti-cells with ascending axons) and chemical
      (GABAergic, NADPH-d/NOS positive, peptide containing cells) defined cell type in
      the neuronal network of the cortex of the rat.

PMID- 7560905
TI  - Synapses of optic axons with GABA- and glutamate-containing elements in the optic
      tectum of Bufo marinus.
AB  - The central termination and the transmitter content of the optic fibers and the
      neurochemical nature of their synaptic targets was investigated in the optic
      tectum of the toad Bufo marinus. Retinal ganglion cells were retrogradely filled
      from the tectum with the fluorescent dye DiI and the retinal wholemounts were
      immunostained for glutamate. Most of the dye-filled cells could be double
      labeled. In addition, double-labeling for gamma-aminobutyric acid an glutamate
      were also made, when colocalization of these markers was not observed in the
      neurons of the retinal ganglion cell layer. In order to identify retinal
      terminals in the optic tectum, optic axons were retrogradely filled with
      horseradish peroxidase. Postembedding immunocytochemistry showed that 88% of the
      optic axon terminals were glutamate-like immunoreactive, 6% gamma-aminobutyric
      acid-immunoreactive and 6% were negative for both GABA and glutamate. Optic fibre
      terminals synapsed on gamma-aminobutyric acid- or glutamate-containing
      postsynaptic profiles (58% and 7%, respectively), while the rest on
      immunonegative elements. Optic fibres containing glutamate rarely synapsed with
      glutamate-like immunoreactive postsynaptic elements. In contrast, 67% of the
      gamma-aminobutyric acid-immunoreactive optic terminals synapsed onto gamma
      aminobutyric acid-positive dendrites. It has been observed after combination of
      anterograde tracer transport and double-label immunocytochemistry, that 57% of
      the optic terminals synapsed on gamma-aminobutyric acid-immunoreactive elements
      and 38% on dendrites containing neither gamma-aminobutyric acid- nor glutamate
      immunoreactive materials. These results suggest that (1) a large number of
      ganglion cells use glutamate and some gamma-aminobutyric acid as a transmitter,
      (2) a substantial proportion of the optic axons terminate on gamma-aminobutyric
      acid-containing inhibitory interneurons in the tectum, (3) some intrinsic neurons
      in the tectum are glutamate-like immunoreactive. We also propose, that (4) gamma
      aminobutyric acid-immunoreactive optic axons may form an effective disinhibitory
      circuit in the tectum by synapsing preferentially with local inhibitory
      interneurons.

PMID- 7560906
TI  - Variations in the formation of the human caudal spinal cord.
AB  - Collection of 15 human embryos between 4-8 developmental weeks was used to
      histologically investigate variations in the development of the caudal part of
      the spinal cord and the neighboring axial organs (notochord and vertebral
      column). In the 4-week embryo, two types of neurulation were parallelly observed
      along the anteroposterior body axis: primary in the areas cranial to the
      neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week
      embryos, both parts of the neural tube fused, forming only one continuous lumen
      in the developing spinal cord. In the three examined embryos we found anomalous
      pattern of spinal cord formation. Caudal parts of these spinal cords displayed
      division of their central canal into two or three separate lumina, each
      surrounded by neuroepithelial layer. In the caudal area of the spinal cord,
      derived by secondary neurulation, formation of separate lumina was neither
      connected to any anomalous notochord or vertebral column formation, nor the
      appearance of any major axial disturbances. We suggest that development of the
      caudal part of the spinal cord differs from its cranial region not only in the
      type of neurulation, but also in the destiny of its derivatives and possible
      modes of abnormality formation.

PMID- 7560907
TI  - Acid, basic and neutral soluble and membrane-bound aminopeptidase activities
      after lidocaine administration in discrete areas of the rat brain.
AB  - It has been suggested that aminopeptidase activity could play an important role
      in the regulation and biotransformation of several neuroactive peptides.
      Lidocaine is a local anesthetic widely used in therapeutics and as antiarrhythmic
      agent. However, information concerning possible alterations in the neuropeptide
      metabolism after treatment with this anesthetic is lacking. This being the case,
      in the present paper we have studied the activities of three aminopeptidases (Asp
      , Leu- and Lys-aminopeptidase) in several brain areas after lidocaine
      administration. The study includes the activities of the soluble and membrane
      bound forms. Soluble neutral and basic aminopeptidase activities show significant
      decreases after lidocaine administration in the frontal cortex. Soluble Lys
      aminopeptidase also shows a significant decrease in the pituitary gland. On the
      other hand, membrane-bound Leu-aminopeptidase activity shows significant
      decreases not only in the frontal, but also in the parietal cortex and in the
      thalamus. These data might suggest that the neuropeptide transmission and/or
      modulation could be activated by lidocaine.

PMID- 7560908
TI  - NADPH-diaphorase-containing cerebrovascular nerve fibres and their possible
      origin in the pig.
AB  - NADPH-diaphorase histochemical technique was applied to demonstrate the catalytic
      activity of nitric oxide synthase (NOS) in the nerve fibers supplying some
      porcine cerebral blood vessels, as well as in ganglia thought to be their
      possible sites of origin. Five sexually mature Large With Polish race sows were
      used. The following blood vessels and their branches were studied: the basal
      cerebral artery, medial cerebral artery, arteries of the circle of Wills as well
      as arteries located in the arachnoidea. The activity of NADPH-d was visualised in
      whole-mount preparations from the above listed blood vessels. The presence of
      NADPH-d was additionally studied in the ganglia of trigeminal nerves, the sensory
      ganglia of vagus nerves, the pterygopalatine and cranial cervical ganglia. NADPH
      d activity was found in nerve fibres supplying all the studied arteries. Larger
      blood vessels, the basal cerebral artery, medial cerebral artery and arteries of
      the circle of Wills possessed very dense NADPH-d-positive nerve plexuses while
      arachnoidal arteries were poorly innervated by only single nerves. The vascular
      nerve fibers formed bundles varying in thickness, from very thick bundles often
      interchanging nerve fibers to quite thin fascicles. Thick bundles were absent
      from the walls of medium sized vessels and small meningeal arteries where only
      smaller fascicles or single fibres occurred. NADPH-d-positive neurons and nerve
      fibres were found in all the ganglia investigated. However, pronounced
      differences in the number of the positive nerve structures were observed between
      the ganglia. In the pterygopalatine, trigeminal and sensory ganglia of the vagal
      nerve the vast majority of neurons were NADPH-d-positive. Numerous NADPH-d
      positive nerve fibers occurred within the pterygopalatine and trigeminal ganglion
      while sensory ganglia of the vagal nerve comprised smaller number of fibres.
      Small numbers of the neurons and moderate numbers of the nerve fibres occurred in
      the cranial cervical ganglion. The intensity of NADPH-d reaction in the
      endothelium was constant independent of the size of the vessels studied.

PMID- 7560910
TI  - Graded postischemic reoxygenation attenuates ischemia-reperfusion-induced nuclear
      and nucleolar damage in lumbosacral dorsal root ganglia neurons. A light and
      electron microscopic study in rabbit.
AB  - Ischemia and reperfusion-induced nuclear and nucleolar changes of the lumbosacral
      dorsal root ganglia neurons were studied in a spinal cord ischemic model of a
      rabbit. Twenty and forty min abdominal aorta ligation followed immediately by
      perfusion fixation, 20 min abdominal aorta ligation followed by 1 h of normoxic
      reoxygenation and 20 min abdominal aorta ligation followed by 1 h of graded
      postischemic reoxygenation were tested. In animals subjected only to a 20 and 40
      min aorta ligation irregularly undulated nuclear membrane and occurrence of dark
      osmiophilic dense clumps often located close to interchromatin granules were
      found. The segregation of the nucleolar granular and fibrillar components became
      apparent but fibrillar centers were almost completely absent. In animals
      subjected to 20 min ligation followed by 1 h of normoxic reoxygenation a high
      number of dense clumps, loosely disseminated throughout the nucleoplasm was
      detected along with almost complete fragmentation and segregation of the
      nucleolus. The application of the graded postischemic reoxygenation has proven
      effective as a neuroprotective and antisegregatory adjunct whereby the nucleolar
      fibrillar and granular components regained almost normal appearance, and the
      occurrence of dense intranuclear clumps was greatly reduced.

PMID- 7560909
TI  - Effects of stobadine on survival, histopathologic outcome and acid-base status
      after global brain ischemia in dogs.
AB  - Present study is designed to examine an effect of Stobadine, a new cell
      protective agent with antiarrhythmic properties, on survival, electron
      microscopic changes in microvasculatory bed of selected brain areas and acid-base
      parameters of arterial blood after global brain ischemia and reperfusion. Forty
      dogs (weighting 6 to 15 kg) were anesthetized using pentobarbital i.v. (5%, 35
      mg/kg). An intubation and controlled ventilation was performed. One catheter was
      placed into v. femoralis (for drug administration), another to a. femoralis (for
      blood samples) and third one into the left common carotid artery (continuous
      brain blood feeding pressure measurement). Each dog underwent an surgical
      obstruction of principal brain-supplying arteries and immediate administration of
      hypotensive agent (Arfonad, 0.062%) resulting in 7 minutes lasting global brain
      ischemia (brain feeding pressure 1.0-1.5 kPa). If survived, animals were killed
      at one (perfusion-fixed for electron microscopy) or three days after ischemia.
      Ultrastructural changes were evaluated at 24 hour of recirculation (control and
      S2 groups only). Vehicle or 1, 2 or 5 mg/kg of Stobadine (group S1, S2, S5 resp.)
      i.v. was given 30 minutes prior to ischemia. Significantly longer survival was
      observed in group S2 (8 of 11 until 72 hour) as compared to control group (none
      of 7, p < 0.005 by Student's t-test). The ultrastructural changes of blood-brain
      barrier structures were none or minimal in S2 (single damage type), but in
      control group three major types of capillary damages has appeared at 24 hour
      after insult. They include intravascular coagulopathy (type I), no-reflow (type
      II) phenomenon with astrocyte edema, and capillary necrosis (type III) finally.
      Stobadine pretreated animals experienced hypercapnia, elevated arterial O2 and
      slight deeper acidemia (depending on dosage) as compared to control group.
      Respiratory compensation of metabolic acidosis was present in control group, but
      lacking in all stobadine pretreated animals. Stobadine at 2 mg/kg improves
      survival (Student p < 0.005, Mantel-Cox p < 0.05, Fischer p = 0.004). Stobadine
      has a protective effect on neurons and structures of blood-brain barrier
      (endothel, astrocytes, basement membrane) seen in electron microscope.

PMID- 7560911
TI  - Pyramidal tract fiber spectrum in rats, with comments on cats and man.
AB  - Most CNS fiber spectrums are unimodal and strongly positively skewed, with many
      small and few large fibers. This study shows that the pyramidal tract (PT) fiber
      spectrum of a rat can be calculated as the sum of three distributions of
      myelinated axons, each derived by normal Gompertzian growth from three normal
      distributions of protoaxons. Histological measurement of the rat PT determined
      the values entered into the model, thus forcing a unique solution. The model was
      generalized to cats and man by assuming values for which no experimental data was
      available; the simulated PT fiber spectrums closely matched the observed PT fiber
      spectrums, in both species. It is concluded that normal Gompertzian growth is
      sufficient to account for the specific shape of the fiber spectrum, with no
      recourse to morphogenetic sculpting. The overproduction of cells during growth,
      and death of cells during development, may regulate the total number of neurons
      in different areas of cortex, but plays no role in determining the specific shape
      of the PT fiber spectrum.

PMID- 7560912
TI  - Crystalloid structures in the neuronal nuclei of the cerebral cortex of rats
      following total ischaemia.
AB  - The study was concerned with the nuclei of neurons derived from the cerebral
      cortex of rats that underwent experimental cardiac arrest for a duration of 10
      minutes and then, after reanimation, survived from 2 weeks up to 10 months. The
      animals were divided into two groups: in the first-those specimens that survived
      from 2 to 6 weeks; in the second-those that survived 8 weeks to 10 months. In the
      specimens obtained from the first group we observed irregular vesicular
      structures and bundles of parallel fibrils 8 nm in diameter. In the second group
      we often observed paracrystalline form resembling "plaited ropes" and tubulous
      structures linked by a microfibrillar netting. These structures were analysed
      with a gonyometer. We believe that both the paracrystalline and the irregular
      vesicular structures that have been observed in the neurons obtained from
      ischaemic brains appeared due to the alterations in the structure of the
      karyoskeleton and that the observed intracellular structures are not specific for
      post-ischaemic alterations.

PMID- 7560913
TI  - An ultrastructural study of the sympathetic preganglionic neurons that innervate
      the superior cervical ganglion in spontaneously hypertensive rats and Wistar
      Kyoto rats.
AB  - Comparative ultrastructural study of the sympathetic preganglionic neurons that
      innervated the superior cervical ganglion (SPN-scg) was made between
      spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto
      rats. After injection of choleragen subunit-B horseradish peroxidase (CB-HRP)
      into the superior cervical ganglion, three types of the sympathetic preganglionic
      neurons were identified according to their ultrastructural features. In both SHR
      and WKY rats, the neurons in the autonomic region of T1-T3 segments of the spinal
      cord showed a characteristic distribution pattern in which the Type I neurons
      were located more laterally in n. intermediolateralis pars funicularistic (ILf),
      and n. intermediolateralis pars principalis (ILp), Type III neurons more medially
      in n. intercalatus spinalis (IC), n. intercalatus pars paraependymalis (ICpe) and
      Type II neurons in n. intermediolateralis pars principalis (Ilp) as well as in n.
      intercalatus spinalis (IC). Of the three types of neurons, there was not
      noticeable ultrastructural difference in Type II and Type III neurons between the
      SHR and WKY rats. Some differences, however, were observed in Type I neurons
      between the two animals stains. In SHR, the nucleus of Type I neurons displayed
      many deep indentations and a greater number of profiles of Golgi apparatus. Three
      types of the axon terminal were found to make synaptic contacts with the labelled
      Type I neurons. Some proportional changes of the different axon terminals were
      observed between those of SHR and WKY rats. The results of this study suggest
      that the suppressive effect on the activity of the sympathetic preganglionic
      neurons in SHR may be attenuated which would result in an unbalanced activities
      of some of neurotransmitters on the sympathetic preganglionic neurons thereby
      leading to the onset of hypertension. The increase in the number of nuclear
      indentations and an increased activity in the Golgi complex may reflect an
      increase in the synthesis of some of the neurotransmitters or neuromodulators in
      the sympathetic preganglionic neurons or their axon terminals. The characteristic
      distribution patterns of the three types of neurons suggest that, of the three
      types of SPN-scg, only the Type I neurons may be implicated in the regulation of
      the cardiovascular system.

PMID- 7560914
TI  - Enkephalin in the caudal PAG of rat: an immunocytochemical electron microscopic
      study.
AB  - Enkephalins are opioid peptides which elicit an analgesic effect when injected
      into the periaqueductal gray matter and in particular into its caudal part. In
      this study we wanted to investigate the fine structure of the neurons and of the
      synaptic circuits involved in the enkephalin action in rats using
      immunocytochemical pre-embedding methods. The labelled neurons show a small
      medium sized soma, with a large nucleus, an absence of an extensive granular
      endoplasmic reticulum and few synaptic contacts. The synapses on enkephalin
      dendrites are often multiple, unlabelled and show both symmetrical and
      asymmetrical junctions. Enkephalin axon terminals make synaptic contacts on
      dendrites, usually unlabelled; contacts between enkephalin elements were
      occasionally seen. The enkephalin synapses show a symmetrical type of junction.
      These data give morphological support to the physiological findings, in
      particular to those suggesting an inhibitory effect of enkephalin on
      periaqueductal gray matter cells through a post-synaptic process. The findings
      are discussed with respect to pain modulation taking into consideration the
      enkephalin synaptic complex in intrinsic circuits and the possible ending of
      enkephalin axons on the projective neurons of the periaqueductal gray matter.

PMID- 7560915
TI  - Synaptic reorganisation of the mediodorsal thalamic nucleus in adult rat
      following chronic prefrontal cortical lesions.
AB  - Chronic changes in the thalamic mediodorsal nucleus (MD) after unilateral lesions
      of the prefrontal cortex were studied with the aid of quantitative light, and
      electron microscopic immunohistochemistry. Three months after the lesions,
      although the size of MD ipsilateral to the lesion did not change considerably,
      the neuronal density was significantly reduced. Conversely, as demonstrated by
      quantitative electron microscopy, the density of GABA immunostained axon
      terminals significantly increased in the lesioned side. It is suggested, that as
      MD does not contain GABA cells, the reactive hyperinnervation of the MD by GABA
      containing axons is of extrinsic origin. This finding is also the morphological
      evidence of the potential of GABA-ergic nerve cells for reactive (induced) axonal
      sprouting.

PMID- 7560916
TI  - Sex, cells, and same-sex desire: the biology of sexual preference. Part I.

PMID- 7560918
TI  - Is homosexuality genetic? A critical review and some suggestions.
AB  - Genetic analysis of behavioral differences among human beings requires both
      careful experimental design and appropriate genetic models. Any genetic study
      must be (1) valid and precise measures of individual differences, (2) appropriate
      methods to ascertain biological relationships, (3) research subjects who have
      been randomly recruited, (4) appropriate sample sizes, and (5) appropriate
      genetic models to interpret the data. In addition, the researchers must exercise
      caution in interpreting biosocial effects from the observed phenotypic
      correlations. To date, all studies of the genetic basis of sexual orientation of
      men and women have failed to meet one or more or any of the above criteria.

PMID- 7560917
TI  - The biology of homosexuality: sexual orientation or sexual preference?
AB  - This paper begins with a summary of the biological research on homosexuality that
      occurred in the late 1980s and early 1990s. It then summarizes the treatment of
      this research chiefly by the print media. It then adumbrates the presuppositions
      about sexuality and gender upon which the reports were based. It is argued that
      the presuppositions, which are asserted without being examined, date back to the
      nineteenth century. They ignore the historical, sociocultural, and humanistic
      research of the last two decades that collectively comprise the field of gay,
      lesbian, and bisexual studies. The discussion of the issue of choice follows and
      it recognizes the various constraints on choice without eliminating it as an
      element of sexual expression. Finally, the paper sets forth a general conception
      of homosexuality that includes its psychological and socio-cultural dimensions
      along with the biological.

PMID- 7560920
TI  - Sexual preference and altruism.
AB  - Several hypothesis have been offered to explain homosexuality. This study tests
      the prediction of the sociobiological model that male homosexuals should be more
      altruistic than heterosexuals. Subjects were dichotomized into homosexual (N =
      76) and heterosexual (N = 51) groups on the basis of self-reported sexual
      feelings and behaviors. Both groups provided demographic information and
      completed Hogan's Scale. As predicted, the homosexuals were found to score
      significantly higher on the empathy assessment. Given the strong association
      between empathy and altruism, the sociobiological model was supported.

PMID- 7560919
TI  - Wilson's Panchreston: the inclusive fitness hypothesis of sociobiology re
      examined.
AB  - Of several hypotheses proposed by sociobiologists to explain "homosexuality", the
      most widely discussed is the inclusive fitness hypothesis, which is examined here
      in the work of the primary sociobiological proponents, E. O. Wilson, Michael
      Ruse, and James Weinrich. After reviewing the basic evolutionary concepts of
      natural selection, adaptation, and inclusive fitness/kin selection, I analyze the
      inclusive fitness hypotheses of homosexuality, taking as an exemplar the initial
      statement of E. O. Wilson. The implicit assumptions is this hypothesis are
      identified: that "homosexuality" is a unitary phenomenon, of direct genetic
      origin, occurring at similar frequencies across societies and through time,
      without direct reproductive gain, with therefore must be of genetic advantage to
      relatives. Each of these implicit assumptions is discussed and assessed in turn.
      The inclusive fitness hypothesis, derived primarily from current stereotypes
      about homosexuals in Western society, is found to be misconceived and without
      scientific merit. A general discussion of the nature-nurture, or essentialist
      social-constructionist, controversy as it involves this hypothesis concludes the
      essay.

PMID- 7560921
TI  - Biological research on sexual orientation: a critique of the critics.
AB  - Evolutionary biologists are tired of being accused of being too biologically
      deterministic, by critics who have little understanding of what biological or
      evolutionary theories actually imply. Misunderstandings came about because social
      science disciplines often do not share evolutionary biology's tendency to build
      into their models multiple "normal" paths of development. Sociobiologists first
      explained homosexuality adaptively because they first try to explain everything
      adaptively. Most nonbiologists are unaware of this very strong evolutionary
      tradition. It is now fashionable to discount scientific objectivity, but there
      are many examples of where such an attack is unwarranted. Kinsey produced a
      nontypological theory of sexual orientation in spite of his history as a
      taxonomist. Sociobiologists produced a nonpathological explanation of
      nonreproductive homosexuality in spite of the centrality of reproductive success
      in their models. In judging whether a discipline is particularly likely to be
      misused in social debates, one must perform the appropriate intellectual
      "controls". One must examine appropriate uses as well as misuses, and one must
      examine other disciplines to see whether there are differences in the relative
      likelihood of abuse. Indeed, many social-science theories have been even more
      clearly abused than biological ones.

PMID- 7560922
TI  - On the history of biological theories of homosexuality.
AB  - Biological theories of homosexuality fit into the discourse on reproduction and
      sexuality that began in the nineteenth century. They arose in the context of the
      early homosexual rights movement, with its claim for natural rights, and the
      psychiatric discussions about sexual perversions. With the classification of
      homosexuality as a distinct category, homosexuals were excluded from the
      "normal". Biological theories of homosexuality were attempts not only to explain
      its causes, but also to maintain the exclusion of homosexuals as the "other".
      Biological explanations can be categorized as genetic, constitutional,
      endocrinological, and ethological. On the one hand, biological theories were used
      in the struggle for homosexual rights. On the other hand, they were used to
      "cure"e homosexuals. Every theory led to a specific therapy. This paper points
      out the roots of this thinking, traces the development of various theories, and
      shows the utilization of biological theories in treating homosexuality.

PMID- 7560923
TI  - Homosexuality, biology, and ideology.
AB  - This paper critically examines the complex relationships and interdependencies
      between biological theories on homosexuality and sociosexual ideologies. It
      challenges the privileged status of biology as the ultimate authority on
      homosexuality. This status is based on the belief that biology is a value-free
      science. On the contrary, this essay shows how unacknowledged assumptions and
      culturally bound patterns of thinking about sexuality taint biological research.
      Sociosexual ideologies are defined as principles that organize the ways we
      express our sexualities and the way we theorize about them in biology. The
      following ideologies are identified: (1) sexuality-as-heterosexuality, (2)
      sexuality-as-reproduction, (3) sexual dualism (male vs. female), and (4) the view
      the homosexuality is a sexual inversion. The process by which these ideologies
      are incorporated into biology is two-fold: (1) as a projective act from society
      onto nature and (2) as a reflective act from nature back into society. It is
      further argued that biological knowledge of homosexuality resulting from that
      process can be used for diverse political interests. Finally, it is proposed that
      since biological theories on homosexuality are inseparable from the context of
      their paradigmatic origin, it is possible that new theories could be derived from
      new ideologies.

PMID- 7560924
TI  - Female or male: the classification of homosexuality and gender.
AB  - During this century the issue of homosexuality has been a recurrent theme on the
      research agenda of biologists. Historically, the life sciences have
      conceptualized homosexuals as persons with characteristics of the opposite sex.
      This paper discusses how the discourse on homosexuality became entangled with the
      discourse on gender.

PMID- 7560925
TI  - Is sexual preference determined by heredity? Introduction.

PMID- 7560927
TI  - Sex, cells, and same-sex desire: the biology of sexual preference. Part II.

PMID- 7560926
TI  - A critique of the possibility of genetic inheritance of homosexual orientation.
AB  - Many workers in human sexuality have tried to discover causes of sexual
      orientation. No one theory has proved to be satisfactory. Studies of monozygotic
      and dizygotic twins, some of whom have been reared separately and some together,
      suggest that there may be an inherited component of homosexuality. Other studies,
      particularly those concerned with the evolution of human sexuality, question such
      a possibility. A further question arises because a large part of the human
      population is neither exclusively homosexual nor exclusively heterosexual. This
      paper will examine the evidence for genetic inheritance presented by twin and
      family studies. It will explore ways in which a gene favoring a homosexual
      orientation but not reproduction could continue to exist in a population. The
      importance of defining terms that refer to sexual orientation will be discussed
      in the context of determining exactly what may be inherited. Finally, the effects
      of accepting genetic inheritance as the cause of sexual orientation will be
      discussed.

PMID- 7560928
TI  - Animals models for the development of human sexuality: a critical evaluation.
AB  - Biological explanations of human homosexuality build upon a theoretical framework
      developed from the study of animals, especially that of rodents. Researchers have
      constructed a physiological model to explain the origin and development of
      "masculine" and "feminine" behavior. According to this model hormones acting at
      critical stages in early development organize cells in key areas of the brain.
      After puberty these hormonally organized brain regions are purportedly capable of
      activation by post-pubertally produced circulating hormones. This model of sexual
      development, called the organizational-activational (O/A) model, has framed
      research on sexual behavior in animals and animal-based account of human behavior
      for more than 30 years. However, evidence from a variety of sources has slowly
      accumulated, requiring modification after modification of the original premise.
      Continuing to use the organizational-activational model now interferes with the
      acquisition of new knowledge. I sketch the outlines of an alternative bio-social
      program for research on the development of sexual behavior in animals.

PMID- 7560929
TI  - Biomedical concepts of homosexuality: folk belief in a white coat.
AB  - Biological and medical tradition teaches that sexuality exists for the sole
      purpose of reproduction. Within this tradition homosexuality has no biological
      significance. It is conceived as a pathological condition wherein a homosexual
      has the internal or external characteristics of the opposite sex. The initial
      search for cross-sex physical characteristics in homosexuals (e.g., wide hips in
      males, wide shoulders in females) failed. The search then focussed on so-called
      sex hormones. It was hypothesized that homosexuals had an excess of hormones of
      the opposite sex. The researchers are now hypothesizing that homosexuals have a
      cross-sex brain organization. To date, no evidence for such cross-sex
      differentiation has been credibly demonstrated. This paper describes the results
      of unsuccessful attempts to replicate studies which are based on the assumption
      that homosexuals have a cross-sexed brain organization due to perinatal hormonal
      factors.

PMID- 7560930
TI  - Hormones and sexual orientation: a questionable link.
AB  - This paper critically reviews the studies which explore a possible causal
      relationship between sex hormones and the development of sexual orientation.
      Early studies focused on hormone measurements in adult men and women. While
      definitive interpretations are hindered by methodological problems, the studies
      as a whole do not support a causal relationship between postnatal hormone levels
      and sexual orientation. More recently, a theory that prenatal hormone levels
      produce varying degrees of brain androgenization and subsequent dimorphic sex
      role behavior has consistently been supported by studies in lower mammals.
      Attempts to generalize the causes of sexual orientation from animals to humans
      have been controversial. Efforts to measure the estrogen feedback as an
      indication of brain androgenization have produced inconsistent results. Studies
      of men and women who experienced defect in hormone metabolism (i.e., CAH and
      testicular feminization) have not found a concurrent increase in homosexual
      behavior. Overall, the data do not support a causal connection between hormones
      and human sexual orientation.

PMID- 7560931
TI  - Does peace prevent homosexuality?
AB  - This study attempted to replicate a series of investigations by Gunter Dorner and
      his associates that concluded that more homosexual men are born in wartime than
      in times of peace. That conclusion is based on Dorner's belief that war induces
      stress in pregnant women and that stress causes a drop in fetal androgen levels
      which in turn leads to the development of a homosexual "orientation". The
      replication not only failed to support the Dorner conclusion but also found that
      even those cities that suffered the most severe bombing during World War II
      showed no evidence of increased numbers of homosexuals. The authors conclude that
      homosexual men can go on loving peace and getting involved in the peace movement.

PMID- 7560932
TI  - Is sexual preference determined by the brain? Introduction.

PMID- 7560933
TI  - Brain research, gender and sexual orientation.
AB  - Recent brain research has revealed structural differences in the hypothalamus in
      relation to biological sex and sexual orientation. Differences in size and cell
      number of various nuclei in the hypothalamus for homosexual versus heterosexual
      men have recently been reported in two studies. We have found that a cluster of
      cells in the preoptic area of the human hypothalamus contains about twice as many
      cells in young adult men as in women. We have called this cluster the sexually
      dimorphic nucleus (SDN). The magnitude of the difference is the SDN depends on
      age. In other human research, two other hypothalamic nuclei (interstitial nuclei
      of the anterior hypothalamus [INAH] 2 and 3) and part of the bed nucleus of the
      stria terminalis (BST) have been reported to be sexually dimorphic in the human.
      Sexual differentiation to the human brain takes place much later than originally
      claimed. At birth the SDN contains only some 20% of the cells found at 2 to 4
      years of age. The cell number rapidly increases in boys and girls at the same
      rate until 2 to 4 years of age. After that age period, a decrease in cell number
      takes place in girls, but not in boys. This causes the sexual differentiation of
      the SDN. This postnatal period of hypothalamic differentiation indicates that, in
      addition to genetic factors, a multitude of environmental and psychosocial
      factors may have profound influence on the sexual differentiation of the brain.
      No difference in SDN cell number was observed between homosexual and heterosexual
      men. This finding refutes Dorner's hypothesis that homosexual males have a
      "female" hypothalamus. However, in a sample of brains of homosexual men we did
      find that an area of the hypothalamus called the suprachiasmatic nucleus (SCN)
      contains twice as many cells as the SCN of a heterosexual group. A recent report
      by LeVay claims that another nucleus, INAH-3, is more than twice as large in
      heterosexual as in homosexual men, whereas Allen and Gorski found that the
      anterior commissure was larger in homosexual men than in heterosexual men or
      women. Preliminary research on male-to-female transsexuals is also discussed. The
      functional implications of these findings in determining adult sexual orientation
      are as yet far from clear.

PMID- 7560934
TI  - Science and belief: psychobiological research on sexual orientation.
AB  - The dominant paradigm that generates support for biological theories of sexual
      orientation has profound conceptual flaws. Not only does it equate the motor
      patterns of copulation in rodents with sexual orientation in humans, it assumes
      that the brain regions that regulate these behaviors in rodents participate in
      governing sexual orientation in humans. Reports of sex differences in the rodent
      brain generate speculation concerning the existence of differences in the human
      brain associated not only with sex but also with sexual orientation. Thus, recent
      years have witnessed numerous attempts to demonstrate that the brains of
      homosexuals exhibit characteristics that are typical of the opposite sex. In some
      cases, these attempt have come decades after persuasive evidence suggested that
      the brain characteristic in question does not differ between the sexes in humans.
      If a particular feature on the human brain does not differ between men and women,
      the phrase "typical of the opposite sex" is meaningless. It is, then, illogical
      to argue-even from the perspective of the biologically deterministic paradigm
      that the feature should be typical of the opposite sex in homosexuals. This paper
      analyzes the assumptions and evidence that support biologically deterministic
      theories of sexual orientation. It is concluded that support for these theories
      derives as much from their appeal to prevailing cultural ideology as from their
      scientific merit. This appeal may explain why seriously flawed studies pass
      readily through the peer review process and become incorporated rapidly into the
      biologically deterministic canon where they remain viable even when replication
      attempts repeatedly fail.

PMID- 7560935
TI  - Sexuality in the brain.
AB  - Research on the biological "causes" of homosexuality focuses primarily upon the
      hypothesis that hormonal influences during fetal life "organize" certain parts of
      the brain which thus become centers for sexual orientation and behavior later in
      life. This paper briefly summarizes criticisms of this research that demonstrate
      little evidence for the operation of such centers and emphasizes alternative
      scenarios for the development of sexual orientation and behavior which have been
      slighted by the biological and medical communities. Finally, I suggest that
      commitment to a belief in a biological mechanism which supports the hierarchy of
      power by those who benefit from that power maintains the viability of the
      hypothesis in the face of negative evidence.

PMID- 7560936
TI  - Biology of bisexuality: critique and observations.
AB  - Differentiation of human sexual orientation, particularly bisexuality, has been
      little studied. Most studies have lumped bisexuals with homosexuals. Those
      examining bisexuals separately have uniformly observed that bisexuals are often
      unlike either heterosexuals or homosexuals. Some authors have overgeneralized the
      results of animal studies as applying to humans. While animal models can provide
      useful hypotheses, human sexual orientation is unique. Therefore, conclusions
      about human sexuality based on animal research are suspect. Human sexual
      orientation is influenced by biological, cognitive, cultural, and subcultural
      variable in interaction, leading to multiple types of heterosexuals, bisexuals,
      and homosexuals. Understanding of human sexual orientation will improve only if
      these factors are accounted for in research and theory. Several studies seem to
      indicate that some bisexuals have a predominantly heterosexual or homosexual
      orientation, but high erotic responsiveness or more "masculine" characteristics,
      leading to versatility in sexual behavior. Early exposure to masculinizing
      hormones seems to predispose human females toward bisexuality rather than
      exclusive homosexuality.

PMID- 7560937
TI  - Dexterity and sexuality: is there a relationship?
AB  - In all the recent research on sexuality, one striking analogy that has been
      largely overlooked is that of sexuality and dexterity. This article is a parallel
      synthesis of the current knowledge of these two subjects. Although there does not
      seem to be a causal relationship between these two traits (a particular dextral
      tendency does not imply any associated sexual tendency, or vice versa), a short
      description of past attitudes and beliefs concerning left-handedness illustrates
      the historical similarity of social bias against homosexuality. Second, a
      discussion of the current scientific information on dexterity and sexuality
      reveals how these tendencies are in fact analogous. Finally, the article
      questions how society can maintain its discriminatory policies against
      homosexuality when it is no more a distinctive trait in human nature than left
      handedness.

PMID- 7560938
TI  - Policing "perversions": Depo-Provera and John Money's new sexual order.
AB  - The use of the drug Depo-Provera (medroxyprogesterone acetate [MPA]) in the
      treatment of sexual minorities, such as sadomasochists, transvestites, sexually
      active children and teenagers, and adults sexually attracted to minors, is the
      latest development in a long tradition of dangerous and crude experimentation by
      psychiatrists and clinical psychologists with biodeterministic and reductionist
      views of human sexuality. Among them is clinical psychologist John Money, whose
      zealous advocacy of such treatments ignores or downplays critical issues of
      ethics, informed consent, and the side effects of the drug. The U.S. Food and
      Drug Administration has failed to effectively regulate such uses of Depo-Provera.
      Public outcry, more stringent regulation, and a new acceptance of the rights of
      sexual minorities are necessary to forestall the imposition of a repressive, new
      sexual order.

PMID- 7560940
TI  - 3rd International Conference of the Hospital Infection Society. London, 4-8
      September 1994. Proceedings.

PMID- 7560939
TI  - Sexual expression: a global perspective.
AB  - Current research into possible biological bases of sexual preference has failed
      to produce any conclusive evidence. These studies omit the influence of
      psychological and sociological factors on sexual expression. They conflate the
      individual with his or her behavior. An argument against the dichotomization of
      sexual expression on the basis of the individual's biological sex or that of his
      or her partners concludes this paper.

PMID- 7560942
TI  - Anthropology and germ theory.
AB  - A small study of biomedical cultural influences which affect the implementation
      of infection control practice was undertaken. The study, between March and
      September 1992, was performed in a 10-bedded paediatric cardiac intensive care
      unit and a total parenteral nutrition (TPN) outpatient clinic in a paediatric
      hospital in London. An ethnographic approach incorporating participant
      observation of six ritualistic practices and semi-structured interviews from
      seven people experiencing hospital-acquired infection was undertaken. A
      phenomenological, analytical method was used in an attempt to give meaning to the
      experience and behaviour of nurses, doctors and parents. The study indicated that
      'germ theory' did not equate to nursing or medical practice but that the culture
      of biomedicine may interfere with infection control knowledge which causes
      conflict of understanding.

PMID- 7560941
TI  - Staff compliance with infection control practices: application of behavioural
      sciences.
AB  - Microbiology and epidemiology have made significant contributions to the field of
      Infection Control. Most nosocomial infections which can be prevented are related
      to inappropriate patient care practices. However, it is extremely difficult to
      implement new infection control policies. To achieve staff compliance, infection
      control should learn from the behavioural sciences. Three related fields have
      been shown to be helpful in this respect: social psychology, consumer behaviour
      and organizational behaviour. Basic concepts from all three fields can be applied
      to the work of infection control for achieving staff compliance; the use of
      social power and the reasoned action model from the field of social psychology;
      the use of participatory decision-making from organizational behaviour; and the
      opinion leaders from consumer behaviour.

PMID- 7560943
TI  - Risk factors for surgical infection.
AB  - In the last century remarkable advances have been made in surgery, associated
      with the lowest recorded rates of infection or sepsis. Many surgical practices
      are time honoured but have little scientific basis to prevent postoperative
      infection whereas some local and systemic factors are well recognized and can be
      modified to lower infection risks. Surgical skill is not easily measurable but
      shorter operations in experienced hands leaving the minimum of tissue damage,
      haematoma or dead space have the lowest infection rates in general surgery: < 2%
      in clean and < 10% in contaminated operations. Adequate surgical scrub,
      appropriate suture materials and antibiotic prophylaxis, perioperative correction
      of dehydration and poor nutrition are examples of effective therapy which can be
      conformed to by all surgeons. Other factors, such as the use of wound guards,
      drains and surgical dressings are less easy to estimate for effectiveness or be
      sure that they could be changed or left out of surgical ritual.

PMID- 7560944
TI  - Viral hazards to and from health care workers.
AB  - Much attention has been directed towards nosocomial transmission of viruses as a
      result of clear evidence of patient-to-staff and staff-to-patient transmission of
      the blood-borne viruses HIV and hepatitis B virus. Although the relatively long
      incubation periods of these viruses, together with the frequency of asymptomatic
      infections, renders problems for surveillance it has been possible to study modes
      of transmission and levels of risk over a number of years. Information on trends
      of incidence of other nosocomial virus infections has been difficult to obtain
      for a number of reasons. Often, an outbreak in the health care setting parallels
      an epidemic in the community. Although it may be possible to define nosocomial
      transmission from recording dates of onset of illness relative to admission date
      and, at times, demonstrate circulation of a common strain by molecular
      techniques, the relative contributions of patient-to-staff and staff-to-patient
      transmission may be difficult to clarify. In this review, details are presented
      of the major viruses associated with nosocomial transmission with examples of
      infections to and from staff where these have occurred. The major defences
      against patient-to-staff and staff-to-patient transmission are awareness of
      potential risks, education and adherence to infection control policies,
      immunization of staff, effective decontamination and sterilization and the
      adoption of 'Universal Precautions' in patient care. In addition, there may be
      occasions when additional measures should be considered including isolation,
      cohorting and the use of specific chemo- and immunoprophylaxis.

PMID- 7560945
TI  - How best to utilize limited resources.
AB  - South Africa's new health policy embraces the primary health care (PHC) approach
      for all its peoples and will include good primary, secondary and tertiary care.
      The policy will hope to provide the highest possible standards of care, yet be of
      a scale and complexity that the country can sustain into the future. There will
      almost certainly be rationalization of many of the tertiary teaching hospitals,
      with inevitable cut-backs in their budgets. This in turn could carry the risk of
      damage to the fabric of these institutions, which might be impossible to repair.
      Medicines offer a simple, cost-effective answer to many health problems in
      Africa, provided they are available, accessible, affordable and properly used. A
      looming problem in African drug markets is inefficiency and waste. The use of
      counterfeit medicines has reached unparalleled heights. It is vital that there
      should be a competent, honest, accountable and independent national drug
      regulatory authority, secured in law, to provide the necessary infrastructure for
      the acquisition of sound medicines. Medicines are central to a sound national
      health policy, but there is great public concern about their costs. Anti
      infective drugs are amongst the most widely used class of drugs in the world.
      Inappropriate use of these agents is widespread and guidelines need to be
      established for their correct use. The control of all medicines in South Africa
      is governed by the Medicines & Related Substance Act of 1965. The Medicines
      Control Council is mandated to ensure that all medicines (including antibiotics)
      available to the public are efficacious, safe and of high quality. An informally
      constituted Antibiotic Study Group has been established in order to monitor
      aspects of antibiotic therapy that impinge on more general issues of public
      health, country-wide. The Antibiotic Study Group has instituted an Antibiotic
      Surveillance Programme to monitor the development of antibiotic resistance
      nationally. In addition the majority of the tertiary teaching hospitals have
      comparable in-house antibiotic control policies to help prevent such resistance
      and to cut costs. These issues need to be debated and resolved. Once in place and
      working effectively, they will in the long-term supply the most cost-effective
      means of providing health care for all.

PMID- 7560946
TI  - Protecting patients when their surgeon or dentist is infected with a blood-borne
      virus.
AB  - The vast majority of surgeons and dentists infected with either hepatitis B or
      HIV do not transmit these infections to patients. When such transmission from
      health care provider to patients does occur, the precise mechanism of
      transmission usually remains enigmatic. Attempts to forestall these rare events
      have produced substantial debate as well as legislative and regulatory
      initiatives. The routine immunization of medical and dental students with
      hepatitis B vaccine will eventually eliminate surgeons and dentists as sources of
      this infection. Serological screening of surgeons and dentists for HIV infection
      has been considered impractical. Thus, emphasis has been placed on enhancing
      measures that reduce the risk of blood contact between health care provider and
      patient. These include developing safer techniques and procedures. When an
      infected surgeon or dentist is discovered, a review of their professional
      circumstances is undertaken. In the US many hepatitis B-infected persons are
      permitted to continue practice; most HIV-infected persons stop performing
      invasive procedures. Not completely reassured, some patients inquire of their
      dentist's or surgeon's HIV antibody status.

PMID- 7560947
TI  - Viral infections in children's wards--how well do we manage them?
AB  - Children are frequently admitted to hospital wards with viral infections. Many
      are not life-threatening to the index case, but the spread to vulnerable patients
      who are already at higher risk should be avoided. To do so requires active
      awareness and availability of rapid diagnosis (i.e. the same day). Cohorting and
      handwashing have been found to be the best measures to prevent spread of
      respiratory syncytial virus (responsible for considerable morbidity every winter)
      in hospital wards.

PMID- 7560948
TI  - How far can the paediatric patient with a serious infection be managed as an
      outpatient?
AB  - Serious infections are often treated by paediatricians with parenteral
      antibiotics. Traditionally, patients receiving parenteral treatment are
      hospitalized. However, hospitalization has a grave negative impact on the child.
      The present article discusses the potential benefits of outpatient treatment of
      serious paediatric infections, together with the logistic approach for such
      treatment. Outpatient treatment for serious paediatric infections may provide an
      excellent medical treatment that both reduces costs and increases the patient's
      quality of life.

PMID- 7560949
TI  - Congenital toxoplasmosis: prevention, screening and treatment.
AB  - Congenital toxoplasmosis is an established cause of abortion, neonatal disease
      and ocular defects presenting in later life. Preventative options include health
      education, immunization and screening of pregnant women and infants with
      appropriate management of cases found to be at risk. Screening requires a
      knowledge of the disease, the test, the treatment and the administration of the
      proposed programme. Treatment can be directed towards the acutely infected
      mother, the infected fetus or infant and the patient with an acute exacerbation
      of ocular toxoplasmosis following congenital infection. Harm-benefit assessment
      of screening programmes designed to prevent congenital toxoplasmosis has produced
      conflicting results. Further research is required into the incidence of acute
      toxoplasmosis in pregnancy and subsequent congenital infection, the frequency of
      neonatal handicap, precise tests for the diagnosis of recent maternal infection
      and the presence of congenital toxoplasmosis and improved treatment of the
      infection.

PMID- 7560951
TI  - Infection prevention strategies for children with cancer and AIDS: contrasting
      dilemmas.
AB  - Infectious complications represent significant challenges for children with
      cancer and those infected with HIV. Although both have similarities in the
      disease- and treatment-related alterations in host defences, there are
      significant differences that can have an impact on the approach to treatment and
      prevention of the dominant infectious complications. An important difference is
      that children with cancer readily recover from neutropenia. Thus, the immune
      deficits are interspersed with intervals of immunological recovery. On the other
      hand, children with HIV infection do not appreciably recover from the
      progressive, immunological changes associated with the underlying HIV infection.
      The loss of cellular and humoral immunity is generally not reversible, and thus
      the risk of infection only increases over time. Bacteria constitute the
      predominant pathogen for paediatric cancer patients but invasive mycoses, viruses
      and parasitic infections are emerging as important pathogens. In paediatric
      cancer patients, strategies have been directed at altering or suppressing the
      endogenous colonization patterns of pathogenic bacteria. The success of this
      approach has been limited and at the expense of selecting for antibiotic
      resistant bacterial infections. Children with HIV infection are at risk of
      developing a wide spectrum of pathogens. Strategies for infection prevention in
      the HIV setting have been directed at specific organisms, generally using more
      specific antimicrobial agents and with greater success.

PMID- 7560950
TI  - Vertical transmission of HIV-1: risks and prevention.
AB  - HIV can be transmitted from mother to child before, during, or after birth, but
      the relative contribution of each route remains unclear. Indirect evidence
      suggests that a substantial proportion of transmission occurs late in pregnancy
      or around the time of delivery. In Europe, the rate of vertical transmission is
      around 15-20% and is associated with maternal HIV status, mode of delivery and
      length of time from rupture of membranes, and breastfeeding. A number of
      interventions to reduce vertical transmission have been suggested including
      avoidance of breastfeeding, caesarean section delivery, disinfection of the birth
      canal, passive and active immunization, and anti-retroviral therapy. Several
      clinical trials to evaluate such approaches are ongoing or being planned. The
      costs of the various options are likely to limit implementation.

PMID- 7560952
TI  - Infections in liver transplantation: risk factors and strategies for prevention.
AB  - Infection affects up to 70% of liver transplant recipients and is the second most
      common complication after rejection and graft dysfunction. Identified risk
      factors for infection include: previous transplantation; type of biliary
      anastomosis; transfusion requirements at surgery; surgical complications;
      duration of operation; duration of postoperative ventilation; serological status
      of donor and recipient; steroid use and serotherapy for rejection; and pre- and
      post-transplant antibiotic usage. The majority of symptomatic infections are
      bacterial and relate to surgery (intra-abdominal, biliary and wound infections),
      ventilation and intravenous cannulae. Cytomegalovirus infections occur in 45-100%
      of recipients but are asymptomatic in the majority. Fungal infections are mostly
      due to Candida albicans but infections due to Aspergillus spp. occur in
      approximately 6% and carry a high mortality. There are very few prospective
      comparative trials of antimicrobial prophylaxis in this patient population. The
      management of these patients needs to be based on such studies.

PMID- 7560953
TI  - Protective isolation: who needs it?
AB  - Infection continues to be a major cause of morbidity and mortality in neutropenic
      patients following chemotherapy or bone marrow transplantation (BMT). Concerted
      efforts have been made to protect these patients from infection during the
      neutropenic period. Elaborate protocols to protect the patient from both
      intrinsic and extrinsic pathogens have been devised, ranging from simple single
      room isolation to laminar air flow units (LAFs), in association with varying
      degrees of antibiotic decontamination of the digestive tract. Comparative rates
      of infection using these techniques have varied in different studies, and their
      use has been somewhat controversial. More recently, prophylactic quinolone
      administration to neutropenic patients has significantly decreased the incidence
      of both Gram-negative septicaemia and pyrexial episodes, probably superseding any
      advantages which may have been conferred by previous regimens. LAFs with high
      efficiency particulate air filtration still appear to be the best means of
      protection against aspergillosis, but are expensive and would not be available
      for the majority of neutropenic patients. They should probably be allocated to
      patients who are most at risk; BMT recipients or others who may be expected to
      have a prolonged neutropenic period.

PMID- 7560954
TI  - Immunotherapy and immunoprophylaxis in bone marrow transplantation.
AB  - Immunotherapy can be defined as treatment directed at augmenting host immune
      defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone
      marrow transplantation (BMT) can be subdivided into three broad categories:
      passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy;
      and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are
      prophylactic and suffer from variability in study design, type of IVIG and dosing
      regimens. Various effects on viral and bacterial infections and graft-versus-host
      disease (GVHD) have been reported but few if any have shown benefit in terms of
      improved patient survival. Moreover the immunomodulatory effect of immunoglobulin
      G preparations is frequently overlooked. With the exception of cytomegalovirus
      (CMV) pneumonitis, there is little evidence of benefit in the treatment of
      established infections and the relative benefits of hyperimmune preparations are
      poorly established. The development of haemopoietic growth factors has led to the
      widespread use of cytokines in BMT. The benefits of these agents both in the
      prevention of fever and infection and as adjuvants to standard antimicrobial
      therapy in established infection (e.g. invasive mycoses) are rapidly becoming
      apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor
      (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to
      accelerate granulocyte recovery following BMT and reduce fever days, antibiotic
      usage and hospitalization. RhGM-CSF appears superior in these respects. The roles
      of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As
      with the much publicised studies using anti-endotoxin antibodies as therapy in
      sepsis, there is little evidence of benefit in the few studies performed in BMT
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560955
TI  - Establishing an infection control structure.
AB  - In studies from the USA it has been shown that infection control can lower
      infection rates by 30%. To achieve this an infection control programme has to be
      given a firm structure. Judging from the opinions presented by an educational
      workshop within the International Federation of Infection Control (IFIC) and from
      the literature there is an international consensus on the basic components of
      hospital infection control. An infection control team, with the task of
      identifying areas of concern, providing or initiating work on written policies,
      educating and advising not only medical staff but also hospital administrators,
      constructors etc., constitutes the backbone of infection control. However, in
      most countries the infection control team, should it exist, is usually
      understaffed. This is false economy, a qualified medical input is a proven
      investment.

PMID- 7560957
TI  - Education and infection control audit.
AB  - Education and training forms an important part of the role of the infection
      control team. It is equally important that the infection control nurse and doctor
      have mechanisms in place to monitor staff utilization of the knowledge gained, in
      their clinical practice. The infection control audit which I have developed in
      Southern Derbyshire has been used in various health care settings over the last
      six years to monitor compliance with local infection control policies. It has
      proved to be a valuable tool in improving standards of infection control
      practice, by providing opportunities for education and generally raising the
      awareness of both staff and managers. Although originally developed for hospital
      use, it has been modified for general practice premises, ambulance stations and
      vehicles, and dental practices.

PMID- 7560956
TI  - Training the work force--models for effective education in infection control.
AB  - The education of hospital staff for infection control is really a form of adult
      education in which there are two important priorities: to teach what the student
      wants to know and to deliver knowledge that the student can use. Techniques
      developed in the industrial and commercial fields can be adapted to deal with
      these issues in the hospital. A 'total quality management' customer survey for
      infection control was conducted to identify services that are considered helpful
      by hospital staff and to identify topics that they want to know about. A 'task
      analysis' was carried out to determine the tasks performed by different
      categories of staff, because an education programme that focuses on tasks the
      staff performed, will be delivering knowledge that they can use. Finally, a
      scheme for identifying strategic areas for education, when a guideline is
      implemented, is described.

PMID- 7560958
TI  - Advances in rapid laboratory diagnosis of infectious endophthalmitis.
AB  - Infectious endophthalmitis is a serious ocular condition which always requires
      rapid medical or surgical intervention. At present this, in a number of
      situations, remains empirical as a consequence of problems inherent in
      unequivocal identification of the causative organism, should one be present.
      Aqueous humor smears and culture have limited value in diagnosis. Vitreous
      samples can often reveal the presence of microbes, but these may not necessarily
      be detected in all cases, principally due to suboptimal sampling or pretreatment
      with antimicrobials which render microbes non-culturable on routine media. Use of
      electron microscopy and/or immunocytochemistry offers an alternative means of
      identification, but these approaches have drawbacks principally associated with
      interpretation. Molecular methods which identify conserved sequences from common
      causative microbes of endophthalmitis, or which can specify whether the organism
      is a bacterium or a fungus may become especially important as diagnostic tools in
      this clinical scenario.

PMID- 7560959
TI  - Infection control programmes--are they cost-effective?
AB  - Infection control (IC) programmes are cost-effective in the long-term but much
      depends on the available resources and the support from management. The funding
      of IC programmes at present is linked to the Microbiology Department and a
      separate budget needs to be established. The best use of resources is to apply a
      risk assessment to each situation which presents and to adapt protocols
      accordingly. For example, the treatment of a carrier or an infected patient with
      methicillin-resistant Staphylococcus aureus cost 374 pounds and 2454 pounds,
      respectively in 1993, the major portion of the cost being due to an increased
      length of stay which was two days and 10 days, respectively. It is more cost
      effective to treat carriers. The other cost-effective investment is in education
      and reinforcement of simple messages. Formal lectures seem to be the least
      effective way of producing long-term effect; frequent ward visits or contacts are
      most effective. Also, there is better compliance when there is a perceived risk
      to the staff themselves. The availability of the IC team to advise helps reduce
      waste and therefore cost. This is particularly true of antibiotic usage where it
      was noted that without guidance, the antibiotic usage increased by 2000 pounds
      per month when compared to a similar period in the previous year. The available
      provisions for IC programmes in the UK are utilized exceptionally well when
      compared with other countries.

PMID- 7560960
TI  - Adenovirus cross-infection: a continuing problem.
AB  - Nosocomial outbreaks of epidemics of adenovirus keratoconjunctivitis are
      frequently reported even though the simple measures to prevent or limit such
      occurrences are well documented. There have been two such outbreaks associated
      with the accident and emergency department (A&E) of a large, urban eye hospital
      in recent years. In the first--involving at least 200 cases--there was a delay of
      two months in initiation of control measures, with consequent potentiation and
      prolongation of the outbreak. The delay resulted because of the time taken for
      isolation of the virus responsible (adenovirus type 8). In the second outbreak-
      23 cases--the use of a rapid diagnostic test--adenovirus immune dot-blot (IDBT)-
      allowed prompt identification of adenovirus and enabled early introduction of
      control measures. Important to this strategy was the routine surveillance of eye
      infections in patients attending the A&E. Many clinicians are reluctant to
      investigate possible ocular adenovirus disease because of the cost and the delay
      involved in isolation of the virus in cell culture. Adenovirus IDBT provides a
      rapid and economic alternative (mean time for IDBT reporting five days compared
      to 33 days for cell culture isolation). Concerns over sensitivity of IDBT (67
      84%) vs. culture are now being addressed with molecular biological approaches to
      diagnosis offering sensitivity close to that achieved by culture (91% vs.
      culture) but with the added advantage of same day reporting.

PMID- 7560961
TI  - Antibiotic treatment of ophthalmic infection: new developments.
AB  - The introduction of quinolones has dramatically altered antibiotic therapy for
      serious ophthalmic infections. The newer cephalosporins are also playing a more
      significant role. The recently introduced macrolides, particularly azithromycin,
      have great potential for treating not only serious infections, but also some of
      the less serious ones. These new developments are discussed, and the cost
      implications of new antibiotic treatment on ophthalmology is described.

PMID- 7560962
TI  - Contact lens wear by hospital health care staff: is there cause for concern?
AB  - Microbial keratitis can occur in association with contact lens wear. The absolute
      risk of infection is low but may be enhanced as a consequence of increased
      exposure to potentially pathogenic microbes in a hospital setting. There is
      variation in risk depending on type of lens worn and its modality of use.
      Extended-wear lenses carry the greatest risk. Pseudomonas aeruginosa and
      Acanthamoeba are causes of potentially devastating ocular infections in contact
      lens wearers. The risk of these infections could be reduced by fastidious hygiene
      practice. Hydrogen peroxide disinfection is recommended when a storage case is
      included in the care regimen. This should be cleaned thoroughly and dried prior
      to disinfection and never exposed to tap water. Daily wear of one-day
      'disposable' soft contact lenses or use of rigid gas permeable lenses is
      recommended for hospital staff. Contact lenses should be removed immediately and
      discarded or disinfected if the eye becomes contaminated and/or use of an eyewash
      is required.

PMID- 7560963
TI  - Inner-city tuberculosis in the USA.
AB  - Tuberculosis (TB) has become more common during the past five years in several
      areas of the USA. Occurrence has been facilitated by the increasing number of
      patients with concurrent HIV infection, by cases due to multiple-drug-resistant
      strains, by incomplete TB therapy among homeless and non-compliant patients, and
      by cases in immigrants from other countries where TB prevalence is high. These
      features mean that the major burden of TB today is being borne by inner-city
      health care facilities that care for the poor. This is illustrated by data from
      Atlanta, Georgia, where a large proportion of the new cases recognized in the
      metropolitan area are reported by Grady Memorial Hospital, the public hospital
      serving the indigent and working poor of the inner city. Similar patterns are
      recognized in the other USA cities where TB has again become a blight. In view of
      these epidemiological features, minimizing inner-city TB will require careful
      attention to diagnosis and isolation procedures in the hospital. Engineering
      changes at hospitals providing acute care of TB have recently been ordered by the
      federal government. These promise to be very expensive, and primarily affect the
      public hospitals, which can least afford them. Innovative treatment programmes
      are essential, as follow-up after acute care is difficult in this setting.
      Directly observed therapy can help, but for some cases the era of the TB hospital
      may have returned. Current attention focuses on legal and ethical issues
      associated with detaining non-compliant and recalcitrant patients to complete
      their therapy. Bacille Calmette Guerin (BCG) vaccine is not a priority for this
      setting at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560964
TI  - Tuberculosis in London: a review, and an account of the work of the London
      Consultants in Communicable Disease Control Group Working Party.
AB  - Tuberculosis (TB) has been recorded in London for centuries but reports have
      declined over the last 100 years, with a 10-fold decrease between 1948 and 1987.
      However, from 1987-1993 notifications of TB in London rose by 34%, compared with
      15% nationally. This rise, together with concerns about undernotification and the
      emergence of multi-drug resistance in New York, led to establishment of a London
      Consultants in Communicable Disease Control Working Party on TB to review current
      surveillance data. Notifications to the Office of Population Censuses and Surveys
      from the London Boroughs declined by approximately 6.5% per year from 1982-1987.
      If this had continued until 1993 there would have been 3579 fewer notifications
      than actually received. The proportion of cases in the 15-44 age group rose
      markedly in males. The proportion of notifications in those aged 65 and above was
      higher in the Thames Regions outside London, where the total TB notifications
      declined by 3.5% over the same period. Recommendations were made to improve TB
      surveillance in London; and a city-wide surveillance function was established in
      1994 to collate and monitor data on TB.

PMID- 7560965
TI  - The scientific basis for using surveillance and risk factor data to reduce
      nosocomial infection rates.
AB  - Research over the past 20 years has demonstrated that an active programme of
      surveillance with feedback of surgical wound infection rates to surgeons can
      reduce subsequent rates by 30-40%. For surveillance data and feedback to be
      meaningful and influential, however, certain rigorous methodological principles
      must be observed. First, surveillance data must be collected in an accurate,
      efficient and confidential manner. This requires written definitions of
      infection, regular clinical case-finding, post-discharge follow up for short
      staying patients, and computer storage, analysis and reporting of the data in
      coded form that does not publicly identify individuals. Second, the variation in
      intrinsic risk of the patients of the various surgeons must be controlled for by
      stratifying the final infection rates on a multivariate risk index, which
      combines the traditional classes of wound contamination with measures of
      intrinsic patient susceptibility. This can be accomplished with a relatively
      small commitment of time by the Infection Control Nurse with the aid of
      sophisticated computer software that is now available.

PMID- 7560966
TI  - The return of Corynebacterium diphtheriae: the rise of non-toxigenic strains.
AB  - With the decline in incidence of diphtheria in Europe and the USA, many
      laboratories no longer routinely culture throat swabs for Corynebacterium
      diphtheriae. However, there is an outbreak of infection with toxigenic strains in
      Russia and most adults do not have protective levels of antibody. Non-toxigenic
      strains are known to cause local disease and lysogenic conversion probably occurs
      in vivo as well as in vitro. Non-toxigenic C. diphtheriae var. gravis, formerly
      quite rare, has been isolated with increasing frequency in the UK over the last
      five years. During prospective screening at one Sexually Transmitted Disease
      Clinic, six (1%) of 578 homosexual men were found to harbour the organism in the
      throat, four of them with clinical pharyngitis. Only one of 1696 heterosexual men
      and women were found to be carriers. Seven cases of endocarditis due to this
      organism were reported in a single year in Sydney, Australia and non-toxigenic C.
      diphtheriae var. mitis has caused four cases of endocarditis in Switzerland. Non
      toxigenic strains are responsible for pharyngitis and occasional invasive disease
      and should be treated. Routine screening of throat swabs should not be abandoned.

PMID- 7560967
TI  - Use of conjugate vaccines to prevent meningitis caused by Haemophilus influenzae
      type b or Streptococcus pneumoniae.
AB  - Antibodies to the capsular polysaccharides of Haemophilus influenzae type b or
      Streptococcus pneumoniae protect against meningitis caused by these bacteria.
      Many of the polysaccharides are poorly immunogenic, especially in infants, but
      can be turned to highly immunogenic vaccines by covalent conjugation to a protein
      carrier. On the basis of the good protection observed in several trials, H.
      influenzae type b conjugates have been accepted for wide use. This experience has
      also provided direction for the development of new conjugates against infections
      caused by the most common serotypes of S. pneumoniae. First results from
      immunogenicity studies of these pneumococcal conjugate vaccines are promising.

PMID- 7560968
TI  - Treatment of multidrug-resistant tuberculosis.
AB  - Recent outbreaks of multi-drug-resistant tuberculosis (MDR-TB) have resulted in
      significant morbidity and mortality in patients with AIDS. The poor outcomes are
      attributable to delayed diagnoses, slow reporting of antimycobacterial
      susceptibility results, inadequate treatment regimens and profound
      immunosuppression. There are no prospective clinical trials which have evaluated
      the optimal treatment of MDR-TB. A retrospective study has shown that in
      immunocompetent patients with secondary MDR-TB, only 56% responded to prolonged
      courses of multiple drug regimens, and 22% died of TB. In patients with AIDS,
      even fewer patients respond, with median survivals of 2-4 months. In general,
      better responses have been associated with in vitro susceptibility of patients'
      isolates. If possible, patients with MDR-TB should receive at least three drugs
      to which their isolates are susceptible for at least 24 months; these regimens
      are likely to include ethambutol, pyrazinamide, a quinolone, and an
      aminoglycoside. Selected patients benefit from surgical intervention combined
      with aggressive chemotherapy. MDR-TB is best prevented by directly observed
      therapy of patients with susceptible organisms and rigorous infection control
      practices in areas of high incidence of MDR-TB. Effective treatment regimens for
      MDR-TB await the development of novel compounds which have better in vitro
      activity against MDR-TB than currently available drugs.

PMID- 7560969
TI  - Epidemiology of candidiasis.
AB  - The increase in infections due to Candida over the past decade is significant.
      This is particularly true for hospitalized patients where the rate of blood
      stream infection due to Candida spp. has increased by almost 500% over the decade
      of the 1980s. This increase is accompanied by a significant excess mortality and
      a prolonged length of stay in the hospital. This trend continues into the 1990s
      where in the US Candida spp. remains the fourth most common blood-stream
      pathogen, accounting for 8% of all hospital-acquired blood-stream infections.
      Notably, more than one-third of candidal blood-stream infections are caused by
      species other than C. albicans. The majority of these infections arise from an
      endogenous focus of colonization; however, the documentation of nosocomial
      transmission or 'cross-infection' and the recognition of resistance to antifungal
      agents pose new and significant problems. Recent studies indicate that Candida
      may be isolated from the hands of 15-54% of health care workers in the intensive
      care unit setting and that the strain of Candida carried on the hands may be
      shared by infected patients. These studies are facilitated by molecular typing
      and careful epidemiological investigation and suggest that cross-infection is an
      important and preventable feature of candidal blood-stream infection. Both
      endogenous and exogenous sources of infection are now well-documented and such
      information should help direct measures to prevent infections in high risk
      individuals.

PMID- 7560970
TI  - Molecular typing of Aspergillus species.
AB  - In the last four years, several molecular typing methods have been applied to
      various Aspergillus species, primarily A. fumigatus and A. niger. Many 'clones'
      or DNA types exist in the environment and in patients. The most discriminatory
      methods appear to be restriction fragment length polymorphism analysis with or
      without specific probes and random amplification of polymorphic DNA analysis.
      Insufficient work on interlaboratory reproducibility has been done. Most patients
      are infected by single DNA types, although occasionally multiple isolates are
      detected. Little work has been done with regard to detailed hospital epidemiology
      using molecular typing methods.

PMID- 7560971
TI  - Continuous ambulatory peritoneal dialysis-associated peritonitis as a model
      device-related infection: phenotypic adaptation, the staphylococcal cell envelope
      and infection.
AB  - During the development of infection, pathogens are translocated from one body
      site to another and so must readily adapt to changing environmental conditions.
      The influence of host environment on bacterial behaviour and virulence gene
      expression is, however, often overlooked. Environmental signals such as
      temperature, pH and nutrient (especially iron) availability which inform
      pathogens of their living conditions thus contribute to both bacterial survival
      and virulence. In the context of medical device-associated infections such as
      peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients, the
      pathogenesis of infection is related to the ability of the infecting organism to
      multiply, to adhere to catheter polymers and host tissues and to evade host
      defences. Coagulase-negative staphylococci (CNS) such as Staphylococcus
      epidermidis are commonly responsible for CAPD-associated peritonitis. Although
      staphylococci cannot grow in commercial peritoneal dialysate solutions, these
      fluids are modified during dialysis and become enriched by a plasma ultrafiltrate
      which can support bacteria growth. Given that growth environment exerts
      considerable influence on bacterial behaviour, the physiology of CNS cultured in
      vitro in a model system employing pooled human peritoneal dialysate and in vivo
      in implanted peritoneal chambers in the rat has been investigated. Using such
      models marked variation in surface physicochemistry, antibiotic susceptibility
      and adherence to catheter polymers has been observed. This plasticity is clearly
      reflected in the cell envelope phenotype of CNS, the study of which has recently
      lead to the discovery of a staphylococcal receptor for the iron-binding serum
      glycoprotein, transferrin.

PMID- 7560972
TI  - Fungal aerobiology: how, when and where?
AB  - While there is undoubted risk of infection in certain hospitalized patients
      following exposure to inhaled spores of fungi such as Aspergillus, the actual
      risk appears to vary with the underlying condition. Secondly, the degree of
      exposure assessed by colony forming units (cfu) per unit of ambient air is not
      predictable. Thirdly, severely immunocompromised patients, mainly the severely
      neutropenic group, are at risk from infection at very low levels of ambient
      Aspergillus spores. From this it can be argued that the latter group requires
      some form of environmental protection or prophylaxis whatever the circumstances.
      At present the best approach is the use of highly filtered ward areas e.g.
      laminar air flow rooms. Monitoring spore loads is unlikely to affect management
      per se provided that the ventilation systems are regularly and effectively
      serviced. In non-neutropenic patients the risk of infection due to colonization,
      for instance of the paranasal sinuses, prior to hospital admission may be as
      great as that occurring due to exposure within hospital and filtration of air has
      a lesser value. The situation may alter, though, even in these patients if the
      risk level is increased by a building programme in the vicinity of ward areas.

PMID- 7560973
TI  - Hazards to laboratory staff posed by fungal pathogens.
AB  - There is sufficient evidence from the literature to demonstrate the risk involved
      in handling the dimorphic pathogens without suitable containment facilities. The
      number of fungi considered a severe hazard is fortunately low, but impeccable
      working practices and continuous vigilance are necessary to minimize accidents
      and to prevent them leading to worse catastrophies. The continuing discovery of
      new opportunistic pathogenic fungi requires frequent, objective and cautious
      review of the hazard groupings to accommodate them.

PMID- 7560974
TI  - 'Fifteen percent of microbiology reports are wrong!': further experience with an
      internal quality assessment and audit scheme.
AB  - Infection control teams critically depend on the quality of the diagnostic
      microbiology laboratories with which they are associated. Internal quality
      assessment (IQA) by specimen resubmission measures the consistency of laboratory
      performance and can be adapted for medical audit, but few laboratories appear to
      include these techniques as part of their quality control procedures. We
      established an IQA scheme in our bacteriology laboratory in May 1989, and the
      mean discrepancy rate for the first two years was nearly 15%. During the next two
      years covered by this report, the scheme was extended to include audit of the
      consistency of medical microbiologists' comments on reports, and a standardized
      scoring scheme was introduced. Results from the scheme are collated and analysed
      thrice yearly, and laboratory techniques altered and extra staff training planned
      to reduce discrepancies. Four thousand four hundred and fourteen specimens (1.4%
      workload) were resubmitted, and 325 (7.4%) gave discrepant results. During the
      two years, the overall discrepancy rate fell consistently from 9.4 to 3.2%. Fifty
      three discrepancies (1.2%) were in microscopy, and 243 (5.5%) were between
      culture results. Substantial decreases in technical discrepancies followed
      training initiatives in sputum bacteriology, and training in anaerobic
      recognition and improved illumination in the anaerobic cabinet. Problems of
      consistent recognition of staphylococci and of urine isolates in mixed culture,
      and of faecal microscopy have proved difficult to eradicate. There was a 20.3%
      discrepancy rate between medical comments, but only 0.4% would have been likely
      to result in different patient outcomes. The cost of running the scheme was 4474
      pounds per annum, equating to a surcharge of 0.058 pounds to each of our routine
      diagnostic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7560978
TI  - Disinfectant testing on surfaces.
AB  - During the last decade a consensus view has evolved in Europe on the quantitative
      testing of disinfectant efficacy in suspension tests, as well as in surface
      tests. Harmonization of the different national test methods is being pursued
      within the framework of the European Committee for Standardisation (CEN/TC216).
      An expert subgroup of the Committee has drafted a test method to measure the
      microbicidal activity of disinfectants on bacteria attached to surfaces. The
      outcome of an initial collaborative study from seven laboratories is that this
      test system yields reproducible results in different laboratories; thus
      fulfilling the requirements for a basic surface disinfectant test.

PMID- 7560977
TI  - A review of the test methods used to establish virucidal activity.
AB  - Testing the efficacy of disinfectants has been the domain of bacteriologists for
      many years. Recently interest has grown in the virucidal effects of
      disinfectants, due to increased awareness of viral infections and concern for
      possible cross-infection. Findings have demonstrated significant differences in
      the susceptibility of certain viruses, particularly non-enveloped viruses, e.g.
      enteroviruses, to disinfectants compared to some bacteria. For example
      Escherichia coli and herpes simplex virus are inactivated by 20% isopropyl
      alcohol (IPA) whereas Staphylococcus aureus requires > or = 50% and poliovirus is
      not inactivated by IPA. Currently there is little or no standardization in the
      methods used for the determination of virucidal activity in suspension, or on
      hands and surfaces. Methods in use in Europe and the USA will be reviewed and
      their relevance to the clinical situation discussed.

PMID- 7560975
TI  - Mycobactericidal testing of disinfectants: an update.
AB  - Tuberculosis, a major killer in developing countries, is on the rise again in
      industrialized nations. AIDS, increased use of immunosuppression and the
      emergence of multiple drug-resistant Mycobacterium tuberculosis (MDR-TB) have
      further enhanced its significance. TB is projected to cause 3.5 million deaths
      per year by 2000. Also, other types of mycobacteria are being incriminated in
      human infections with increasing frequency. Thus, the enhanced risk of nosocomial
      and iatrogenic spread of mycobacteria is forcing a review of infection control in
      general and claims of mycobactericidal activity of disinfectants in particular.
      Mycobacteria are more resistant to disinfection than enveloped viruses and other
      types of vegetative bacteria, but a proper comparison with non-enveloped viruses
      requires more data. Flaws in currently used protocols for mycobacterial activity
      are: (i) a lack of proper quantitation; (ii) unrealistically long contact times
      at higher than ambient temperatures; (iii) absence of a suitable organic load;
      (iv) ineffective neutralizers; (v) unsuitable surrogates for M. tuberculosis;
      (vi) improper recovery media; and (vii) inappropriate types of carriers.
      Furthermore, we have recently found a product meant for 14 day reuse to become
      non-mycobactericidal after only a week under actual use in an endoscopy unit.
      These considerations make the available data on product efficacy unreliable,
      especially in view of the increasing threat from MDR-TB. Recent findings suggest
      that the use of Mycobacterium terrae as a surrogate, better recovery media, flat
      surfaces as carriers, elimination of neutralizers, proper removal of cell clumps
      and a required > or = 4 log10 reduction in the number of colony forming units of
      the test bacterium after disinfectant treatment should make mycobacteridal tests
      more precise and reliable, thus making product registration and selection easier.
      There is also an urgent need to develop standardized protocols to determine the
      mycobactericidal activity of disinfectants under conditions of reuse.

PMID- 7560976
TI  - Methodology for HIV disinfectant testing.
AB  - Due to the variation in protocols from studies by different workers for the
      inactivation of HIV by chemical disinfectants, only limited comparisons of the
      results can be made. These variations include those which apply to disinfectant
      testing in general, such as the level of organic load and the form of
      neutralization of the disinfectant, and those which apply particularly to HIV
      inactivation, such as the method used to detect infectious virus. Our suspension
      and carrier tests to assess the efficacy of chemical disinfectants against HIV
      are described and problems with the interpretation and applicability of the
      results are discussed.

PMID- 7560980
TI  - Reprocessing of anaesthetic and ventilatory equipment.
AB  - Uniform and standardized recommendations for reprocessing of anaesthetic and
      ventilatory equipment are still lacking. The uncertainty in this field is
      underscored by the various methods which are described in the literature which
      include pasteurization, immersion baths, formaldehyde cabinets, automated
      washers/disinfectors and sterilization procedures like autoclaving, ethylene
      oxide and gaseous formaldehyde. Based on the classification of anaesthetic and
      ventilatory equipment as semi-critical items, high level disinfection must be
      regarded as the appropriate decontamination procedure. In contrast to automated
      washers the other above-mentioned disinfection procedures lack an integrated and
      all inclusive reprocessing cycle which consists of cleaning, disinfection,
      rinsing and drying. In view of the increasing demands of employee safety,
      environmental suitability, cost-effectiveness and quality assurance in hospital
      hygiene, only automated washers/disinfectors--either based on hot water
      disinfection or chemothermic processing--fulfil the basic requirements for safe
      and standardized reprocessing of anaesthetic and ventilatory equipment.

PMID- 7560979
TI  - New insights into the pathogenesis of ventilator-associated pneumonia.
AB  - Colonization of the lower respiratory tract of critically ill patients with Gram
      negative bacilli is an early stage in the pathogenesis of ventilator-associated
      pneumonia. Recent studies have emphasized the endogenous source of these bacteria
      and have pointed to the upper gastrointestinal tract as a major source. Gastric
      bacterial overgrowth is known to be promoted by raised intragastric pH. Further
      evidence suggests that duodenal reflux is just as important in gastric bacterial
      overgrowth and subsequent colonization of the mechanically ventilated lung. Work
      on the biomaterials lining the inside of the tracheal tube in critically ill
      patients has shown that this biofilm can be scattered many centimetres as a
      result of ventilator gasflow. In vitro and in vivo evidence has been found to
      support a fluid dynamic process that results in dissemination of tracheal tube
      biofilm, which also contains neutrophils and their contents. The dissemination of
      combined bacteria, effete neutrophils and their breakdown products into already
      compromised lungs may explain the complexity of the clinical condition known as
      ventilator-associated pneumonia. It may thus be more correct to refer to the
      condition as 'ventilator-induced pneumonitis'.

PMID- 7560981
TI  - The impact of surveys on hospital infection.
AB  - The major impact of surveys of hospital infection has been the improvement in the
      quality of infection control programmes. The earlier surveys became an incentive
      to others to find out their infection rates and risk factors for infection.
      Surveys are now more sophisticated in design and the surveillance methods more
      refined, but they have had little impact on the rates of infection. Without
      doubt, the greatest improvements have been made by carrying out targeted
      surveillance with interpretive feedback to clinical staff. This has led to the
      use of guidelines for good practice and measures of outcome. This strategy has
      been shown to decrease infection rates, decrease the need for antibiotics
      therapy, alleviate morbidity and save on hospital costs.

PMID- 7560982
TI  - Prevention of prosthetic valve endocarditis.
AB  - Prosthetic valve endocarditis (PVE) has been traditionally divided into early
      (EPVE) and late (LPVE) forms, the division being made at 60 days after operation.
      Recent actuarial studies suggest that the risk of EPVE continues up to 12 months
      after operation. This new insight must increase the emphasis on perioperative
      prevention, including those measures taken at the time of operation, such as
      antibiotic prophylaxis, and particularly, the prevention of postoperative
      nosocomial bacteraemia which other recent studies suggest is a much more
      significant factor than previously appreciated. The application of DNA-based
      typing methods of the predominant causative organisms of EPVE [coagulase-negative
      staphylococci; (CNS)] can be increasingly expected to unravel the aetiology of
      EPVE and support more logical preventive measures. As with the prevention of
      native valve endocarditis, the prevention of LPVE currently relies on antibiotic
      prophylaxis at predictable times of bacteraemia. Epidemiological studies have
      shown that events currently recognized account for a very minor proportion of
      cases. The elucidation of the incidence, causes and potential preventive measures
      of the spontaneous bacteraemias responsible for most cases of LPVE remains a
      major task. The prevention of all forms of PVE is presently inadequate. Recent
      studies have not improved our abilities but have served to define areas in which
      existing measures should be re-emphasized and other areas in which more knowledge
      is urgently required.

PMID- 7560983
TI  - The increasing significance of outbreaks of Acinetobacter spp.: the need for
      control and new agents.
AB  - Acinetobacter spp. are Gram-negative non-fermentative bacteria which may be
      isolated as commensals from human skin, throat and intestine but are also
      increasingly responsible for hospital infections. Owing to frequent changes in
      their taxonomy, their pathogenic role in humans has not been clear but today
      acinetobacter is considered to be a significant nosocomial pathogen in outbreaks
      of hospital infections predominantly in intensive care units. Nosocomial
      infections due to acinetobacter include urinary tract infections, bacteraemia,
      wound and burn infections, but also they are frequently isolated from ventilator
      associated nosocomial pneumonia. The frequency of hospital outbreaks of
      acinetobacter infections has required the development of reliable typing methods.
      As well as conventional 'phenotypic' methods (serology, biotyping, phage typing),
      'genotypic' systems (ribotyping, plasmid profiles, pulsed-field gel
      electrophoresis) have been utilized for strain identification. These typing
      systems should allow a better understanding of the epidemiology of acinetobacter
      in the hospital environment, e.g. sources, modes of transmission, and result in
      more efficient preventive measures. Acinetobacter infections are difficult to
      treat owing to their frequent multiple resistance to the antibiotics currently
      available for the treatment of nosocomial infections; various mechanisms of
      resistance to beta-lactams and amino-glycosides have been identified in the
      genus. Combination therapy is usually recommended for treatment of acinetobacter
      nosocomial infections and active antibacterials include imipenem, ceftazidime,
      amikacin and the newer fluoroquinolones. Careful in vitro testing of the activity
      of combinations of these drugs is recommended prior to their use.

PMID- 7560984
TI  - The emergence of epidemic, multiple-antibiotic-resistant Stenotrophomonas
      (Xanthomonas) maltophilia and Burkholderia (Pseudomonas) cepacia.
AB  - Stenotrophomonas (Xanthomonas) maltophilia has recently emerged as an important
      nosocomial pathogen in immunocompromised cancer patients and transplant
      recipients. S. maltophilia has been documented as a cause of bacteraemia,
      infections of the respiratory and urinary tracts, meningitis, serious wound
      infections, mastoiditis, epididymitis, conjunctivitis and endocarditis. The
      reservoir of S. maltophilia and the mechanisms by which it is transmitted, remain
      largely unknown. Risk analysis has shown that mechanically ventilated intensive
      care unit patients, receiving antibiotics especially carbapenems, are at
      increased risk of colonization/infection. Because of the in vitro resistance to
      many commonly used agents, it is essential that S. maltophilia is isolated and
      identified correctly. Over the last decade Burkholderia (Pseudomonas) cepacia has
      become a major threat to the management of patients with cystic fibrosis (CF).
      The spread of B. cepacia through previously stable CF clinic populations, is an
      increasing cause for concern. Anxiety has arisen following the observation that
      some patients with previously mild disease, experience an accelerated and fatal
      deterioration in pulmonary function with fever, necrotizing pneumonia, and in
      some cases septicaemia. Early UK surveillance studies suggested a maximum
      prevalence of 7%, though this has risen in recent reports to approach the 40%
      described in the US. Mounting evidence of person-to-person transmission has led
      the Cystic Fibrosis Trust to issue guidelines for the management of colonized
      patients. In an attempt to monitor and understand the spread of B. cepacia,
      typing techniques such as ribotyping have been employed. Because of these
      problems, together with multiple-antibiotic resistance, there is an urgent need
      to identify the major routes of transmission, colonizing, pathophysiological and
      immunological factors.

PMID- 7560985
TI  - New threats to the control of methicillin-resistant Staphylococcus aureus.
AB  - Several countries have achieved considerable success in the control of epidemic
      methicillin-resistant Staphylococcus aureus (MRSA). However, in several hospitals
      in the UK, MRSA strains of enhanced epidemicity, notably EMRSA-16, are becoming
      endemic. Our inability to eliminate the cause of a single-strain outbreak is
      unfamiliar and unnerving. Factors in 'market-led' health care delivery that
      hinder control of MRSA include a shortage of inpatient beds, patients moving from
      ward to ward, and more mixed-specialty wards. Increasing use of day treatments
      leaves an inpatient hospital population with more risk factors for infection.
      Early discharge of infected patients to convalescent homes, or to homes for the
      elderly, has created a new reservoir of infected and colonized patients. The
      emergence of high-level mupirocin resistance may soon also contribute to failure
      of control. The transfer of vancomycin resistance from Enterococcus faecium to a
      laboratory strain of S. aureus suggests that, especially in hospitals with both
      vancomycin-resistant enterococci and MRSA, there is the opportunity for the
      emergence of vancomycin-resistant MRSA for which there may be no effective
      antimicrobial prophylaxis or treatment. It is increasingly important to persuade
      hospital managers that even partial control of MRSA, whilst expensive, is still
      cost-effective and is a quality issue for individual hospitals. The control of
      EMRSA-16 in one hospital has recently been estimated to have saved more than
      629,000 pounds extra costs. MRSA continues to be at the forefront of those
      organisms that seriously challenge modern technological medicine and surgery.

PMID- 7560986
TI  - Penicillin-resistant pneumococci--an emerging threat to successful therapy.
AB  - Pneumococci highly resistant to penicillin G [minimum inhibitory concentration
      (MIC) > or = 2 mg L-1] have become prevalent in many parts of the world since
      their emergence and spread in the late 1970s. In the USA, such organisms are seen
      primarily in two populations: infants and children, and adults with AIDS. Surveys
      in both rural and urban areas have revealed presence of these organisms, as well
      as an increasing frequency of Streptococcus pneumoniae strains relatively
      resistant to penicillin (MIC 0.1-1.0 mg L-1--now defined by some as
      'intermediate' resistance). Predisposing factors are not yet clear. Prior
      antimicrobial therapy was given to some of the children and most of the adults
      who are colonized or infected with resistant strains. Prior or concurrent use of
      cotrimoxazole prophylaxis for Pneumocystis carinii pneumonia has been frequent in
      our cases in adults, most of whom had a concurrent diagnosis of AIDS. Children
      with disease often have a history of long-term prophylaxis with a beta-lactam
      drug (for sickle cell disease, etc). Many strains are also resistant to newer
      cephalosporins like cefotaxime and ceftriaxone (MIC > or = 2 mg L-1). The
      organisms are frequently multi-resistant, with high MIC values common as well for
      chloramphenicol and variable for tetracycline, macrolides, cotrimoxazole, and
      fluoroquinolones. Only to vancomycin are the organisms consistently susceptible.
      These findings raise alarms about the future of pneumococcal disease in both
      community and nosocomial disease. Increasing prevalence in otitis and pneumonia
      in children and in community-acquired pneumonia in adults may lead to use of
      vancomycin as empirical therapy for these clinical situations. This would
      increase the selective pressure for emergence of vancomycin-resistant organisms,
      whether S. pneumoniae or others. Moreover, the pneumococcus was a common cause of
      hospital infection prior to the introduction of penicillin. The potential now
      exists for nosocomial pneumococcal infection again to become a feared and ominous
      occurrence.

PMID- 7560987
TI  - The emergence of Enterococcus faecium resistant to glycopeptides and other
      standard agents--a preliminary report.
AB  - We describe the emergence of vancomycin-resistant (VmR) Enterococcus faecium on a
      liver unit. Over a 22 month period, 110 patients acquired VmR E. faecium.
      Ribotyping identified 116 patient isolates. Five ribotypes accounted for 78% of
      patient isolates, the maximum number of patient isolates of a single ribotype was
      37, and five clusters of four ribotypes were found. Seven patients acquired more
      than one ribotype. Environmental sampling yielded VmR E. faecium of the same
      ribotype as concurrent patient isolates. Clinical specimens from 38 liver
      transplant patients yielded VmR E. faecium and these were compared to 29 who
      acquired vancomycin-sensitive (VmS) E. faecium. Logistic regression analysis
      indicated that duration of admission was the only independent risk factor for
      acquisition of VmR E. faecium.

PMID- 7560989
TI  - Hyperemesis hiemis--a sick hazard.
AB  - Epidemic non-bacterial gastroenteritis or winter vomiting disease is a well
      recognized clinical syndrome causing significant morbidity in the general
      population and in semi-closed communities. The Norwalk group of viruses has
      become established as the aetiological agents responsible for this important
      clinical syndrome. As a result of their historically poorly-defined taxonomic
      status they have been alternatively described as small round structured viruses
      (SRSVs) which allow their differentiation from other morphologically distinct
      small round viruses, e.g. astroviruses, and classical human enteric
      caliciviruses. The Norwalk viruses are highly infectious, give rise to high
      secondary attack rates through person-to-person transmission and are common
      causes of outbreaks in hospitals leading to either ward or hospital closures.
      Transmission occurs via the faecal/oral route but also, and probably more
      importantly, from projectile vomiters, through environmental contamination.
      Inhalation of aerosolized virus arising from projectile vomiters is a possibility
      which requires further study. Laboratory diagnosis is currently achieved by
      electron microscopy but the recent molecular characterization of this group of
      viruses will allow the development of sensitive and specific assays. The future
      control of hospital outbreaks will rely heavily on effective control of infection
      procedures.

PMID- 7560988
TI  - Respiratory syncytial virus--is it preventable?
AB  - Respiratory syncytial virus infection spreads readily among hospital wards,
      nurseries and intensive care units. Careful handwashing is the cornerstone in the
      prevention of nosocomial transmission. Use of rapid diagnostic tests permits the
      cohorting of patients and staff which has been shown to limit the spread in
      hospital wards. In addition, the use of gowns and gloves and limiting visitors
      have been recommended. In the future passive immunization with respiratory
      syncytial virus (RSV) immune globulin or RSV vaccination may be helpful in high
      risk patients.

PMID- 7560990
TI  - Acellular pertussis vaccines--a question of efficacy.
AB  - Whole cell pertussis vaccine is considered to offer at least 80% protection
      against typical whooping cough. The quest for an equally effective but less
      reactogenic vaccine is now drawing to a close. During the forthcoming year a
      number of efficacy trials of acellular pertussis vaccines will be terminated. A
      variety of vaccines containing one, two, three or five purified pertussis
      antigens are being tested in Germany, Italy, Senegal and Sweden. About 30,000
      infants have been enrolled in placebo-controlled studies and more than 100,000 in
      whole cell vaccine-controlled trials. The final plans for analysis of a Swedish
      placebo-controlled trial of whole cell and acellular vaccines is presented. Due
      to the unexpected high incidence of pertussis in Sweden during 1993-1994,
      relative risk comparisons between vaccines will be attempted in that trial, in
      addition to estimating absolute efficacy. A crucial issue is to what extent data
      may be compared between trials, given differences in design, vaccination
      schedules, and chosen endpoints. A primary case definition of laboratory
      confirmed pertussis with at least 21 days of paroxysmal cough have been adopted
      in most trials. Pre-planned meta-analysis using this single endpoint will
      facilitate comparisons between vaccines. Serological correlates to protection in
      individuals will be sought in the ongoing placebo-controlled trials. The concept
      of a serological correlate valid for a vaccinated population but not necessarily
      for the vaccinated individual, as is the case with Hib vaccines, may turn out to
      be the only alternative to performing large efficacy trials in the future.

PMID- 7560991
TI  - BCG--mass or selective vaccination?
AB  - After years of decline, notifications of tuberculosis in England and Wales have
      recently increased. BCG immunization forms part of the programme of measures to
      control tuberculosis in this country. All tuberculin negative 10-13-year-old
      schoolchildren are offered vaccination. In addition BCG is offered selectively at
      any age to those considered to belong to groups at increased risk of
      tuberculosis. While the protective effect of BCG immunization in the population
      of this country is well established, the cost-effectiveness of the School's BCG
      programme has been the subject of considerable debate. If the rate of
      tuberculosis notifications in the 15-29-year-old age group within the white
      majority population, the major group to whom any potential benefit of the
      Schools' programme applies, continues to decline, serious consideration should be
      given to discontinuing this programme while strengthening the programme of
      selective immunization.

PMID- 7560992
TI  - The disposal of clinical wastes.
AB  - The disposal of clinical wastes is often poorly conducted and inadequately
      supervised despite the publication of clear and definitive working guidelines and
      the introduction of increasingly stringent legislative control. The move away
      from landfill disposal of clinical wastes, and the further development of high
      temperature incinerators able to meet increasingly tight emission limits, is to
      be applauded but has inevitably increased the cost of waste disposal. Moreover,
      such developments fail to address the continuing 'shop floor' problems whereby
      wastes enter an inappropriate waste stream or colour coded wastes containers are
      used for inappropriate purposes thus undermining the value of a nationally
      approved hazard warning policy. The development of newer waste treatments,
      including microwave exposure of macerated wastes, may reduce costs and aid in the
      control of environmental pollution. However, stringent control of this and
      existing technologies remains essential. Additionally, increasing resources must
      be directed to improvements in primary waste disposal practices whereby all
      health care staff have a clear responsibility to ensure correct disposal of
      wastes without risk to themselves, their colleagues and others, or to the
      environment.

PMID- 7560993
TI  - Current legislation governing clinical waste disposal.
AB  - The paper considers UK and EC Legislation regulating clinical waste disposal. The
      legal definition of clinical waste is distinguished from both 'health care waste'
      and 'infectious waste'. Waste can be pre-treated so as to enable it to be
      disposed of through the normal waste stream. The legislation is looked at by
      reference to (i) production and storage; (ii) handling and transportation; and
      (iii) disposal. It is vitally important to draw up a waste management strategy.
      Effective segregation at source is a key factor in the waste management strategy
      and it will enable hospital authorities to make economic savings in waste
      disposal costs. The Paper considers the Duty of Care under the Environmental
      Protection Act 1990 and stresses the obligation on each person in the waste
      disposal chain to discharge the Duty. Landfilling as a method of disposal is
      discouraged except for waste where no possibility of infection arises. There are
      problems with hospital incinerators meeting modern emission standards.
      Requirements for licensing new incinerators are examined. The new Waste
      Management Licensing Regulations 1994 require applications for Waste Management
      Licenses to demonstrate technical and financial competence as 'fit and proper
      persons'. The Paper concludes by examining penalties for breach of regulatory
      provisions.

PMID- 7560994
TI  - Mycobacterial contamination of fibreoptic bronchoscopes.
AB  - Because of the increasing numbers of immunosuppressed patients and the general
      resurgence of mycobacterial infection, diagnostic bronchoalveolar lavage (BAL)
      using a fibreoptic bronchoscope is an important and frequent procedure. A
      contaminated bronchoscope may introduce spurious mycobacteria into specimens
      causing diagnostic confusion, infect the patient with mycobacteria, or be a
      vehicle for cross-infection. Bronchoscopes are difficult to disinfect adequately
      if they are not properly cleaned (which may include stripping down channel
      valves) or are damaged. Bronchoscope washers have also contributed to the problem
      when glutaraldehyde becomes too dilute or they become heavily contaminated with
      environmental mycobacteria. Future solutions to prevent contamination include the
      regular maintenance of bronchoscopes and washers, having adequate cleaning and
      disinfection protocols and ensuring that they are adhered to, improving
      bronchoscope and washer design, and developing alternative disinfectants or new
      ways of using current ones. All these will probably have considerable cost
      implications for hospitals.

PMID- 7560995
TI  - Endoscope decontamination: automated vs. manual.
AB  - Automated endoscope washer disinfectors are widely used for the decontamination
      of flexible endoscopes. They are more effective than manual techniques and reduce
      the likelihood of skin contact with irritant disinfectants. Suitable machines are
      those which effectively clean, disinfect and rinse all channels and external
      surfaces without damaging the instrument. If glutaraldehyde is used, fumes should
      be removed or contained to protect endoscopy and processing staff. Machines
      should also be equipped with a self-disinfect facility and the rinse water should
      be of a suitable microbiological quality for the instruments processed, i.e.
      bacteria-free (sterile or filtered) water should be used for bronchoscopes and
      all invasive endoscopes. The choice of machine and cycle will depend on the
      following: whether a mobile or fixed unit is required; the type of disinfectant
      used; instrument throughput; and whether or not it is necessary to process more
      than one endoscope at a time. Purchasers are advised to request independent test
      reports which substantiate manufacturers' claims.

PMID- 7560996
TI  - The prevention of orthopaedic implant and vascular graft infections.
AB  - The infection rate for any surgical prosthesis insertion should be less than 1%
      in the first postoperative year. If infection occurs the patients will lose their
      new found mobility, lose their independence, be hospitalized with sepsis, both
      local and systemic, and perhaps die. Preoperative and intraoperative measures to
      prevent infection are well established in orthopaedic surgery but less
      scientifically applied in peripheral vascular surgery. In both specialties the
      problem of late infection has promoted research on the protection of the peri
      prosthetic environment against both bacteria and biofilm. In orthopaedics, the
      incorporation of various antibiotics into bone cement is well accepted in
      revision surgery, but still debated for the primary operation. On-going research
      on bioresorbable ceramics and the incorporation of antibiotics more effective
      against coagulase-negative staphylococci should eventually counter late
      infections. As HIV-positive patients increasingly present with sepsis around
      implanted prostheses this need will increase. In vascular surgery as the risk
      factors for biomaterial infection are better understood, new generations of
      protein-sealed grafts are permitting ionically compatible antibiotic coatings.
      Large well-designed clinical trials have begun and are needed to confirm the
      forecast of improved long-term clinical outcomes.

PMID- 7560997
TI  - Endoscope decontamination: where do we go from here?
AB  - Thorough cleaning and disinfection or sterilization of endoscopes and associated
      equipment will reduce the likelihood of misdiagnosis and post-procedural
      infection. It will also prevent instrument deterioration and malfunction. With a
      rapid escalation in demand for endoscopy, particularly that associated with
      minimally invasive surgery, it is important that we have the processing
      technology to match the diagnostic and therapeutic value of these instruments
      without exposing staff and patients to unnecessary risk. Wherever possible staff
      should purchase heat tolerant endoscopic equipment that is readily accessible for
      cleaning. Automated processors, e.g. washer disinfectors and ultrasonic cleaners,
      improve the quality of the decontamination process but machines must have a self
      disinfect function to prevent instrument recontamination during processing.
      Sterile, or filtered bacteria-free, water is essential for bronchoscopes and
      invasive instruments. Glutaraldehyde is still the most widely used disinfectant,
      particularly for the heat sensitive flexible endoscopes, but it is irritant and
      sensitizing and a safer alternative is sought. Peracetic acid is more rapidly
      efficacious and probably less irritant and, provided it does not damage
      endoscopes and processing equipment, may prove a suitable alternative.
      Unfortunately there are no nationally agreed test methods for assessing this and
      other new endoscope disinfectants and therefore no register of suitable or
      approved products. There is also no proven safe alternative to ethylene oxide for
      sterilizing invasive heat labile flexible endoscopes. It is important that, if
      toxic disinfectants and sterilants are used, staff and patients are suitably
      protected from exposure. Update training is essential for all processing staff if
      infection risks are to be minimized and sensitization problems avoided.

PMID- 7560998
TI  - Towards European Union standards in hospital infection control.
AB  - Some providers of health care within the European Union (EU)--whether public or
      private--seem to give little priority to the establishment of quality control and
      common standards for infection control. Though uniform practice of infection
      control in hospitals was recommended by The Council of Europe no formal
      declaration about conformity or quality assessment of this important area seems
      to have been actively promoted within the EU. This is the setting against which
      local, and even international infection control protocols are promoted and
      discussed mainly by dedicated individuals and within informal groups, which may
      be endorsed by professional societies. So far no definite attempt to formulate
      European coordination has been recognized apart from initiatives taken by the
      World Health Organization (WHO) regional office for Europe. We may have a long
      way to go towards EU standards for infection control even though the benefits of
      European cooperation in the field of infection control have been recognized, and
      there are still serious doubts within the medical profession as to the
      feasibility of harmonization of these activities. EU standards in hospital
      infection control should be based on the best documented evidence and set at an
      appropriate level allowing wide participation. The medical profession must be
      involved and the inclusion of indicators of outcome must be considered.

PMID- 7560999
TI  - Progress with establishing and implementing standards for infection control in
      the UK.
AB  - The process of agreeing standards for infection control in England and Wales is
      described. To ensure ownership of these standards an extensive consultation
      exercise was undertaken. Further development has been left to Infection Control
      Teams (ICTs) and the relevant health care workers. Management and Consultants in
      Communicable Disease Control were also sent the standards to further encourage
      support for their implementation. The results of a questionnaire of ICT resources
      and activities is alluded to and these data will be a valuable point of reference
      to monitor changes in the status quo of a rapidly changing health service.

PMID- 7561000
TI  - Success, failures and costs of implementing standards in the USA--lessons for
      infection control.
AB  - In the US, extensive standards for performance and 'guidelines for practice' have
      been instituted by a number of governmental and non-governmental agencies. New
      governmental plans for health care depend heavily on practice guidelines, and the
      Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has been
      especially enthusiastic about continuous quality improvement. Monitoring the
      appropriateness of care and altering physician practice appeals to insurance
      carriers and health care management organizations. Some initial data exist to
      show that the quality of health care has been enhanced by these regulations. The
      total cost for health care administration in 1990 in the USA was 24.8% of each
      hospital's spending for health care. Much of this was associated with spending
      for new initiatives in practice guidelines, physician profiling, quality
      assurance, and the like. Few data exist to show that the quality of health care
      or hospital infection control has been enhanced by these expenditures.
      Regulations and guidelines also have proliferated in infection control. Guides
      from the JCAHO have been expanded, and recent mandates from the Occupational
      Health and Safety Administration (OSHA) for protecting employees from blood-borne
      and respiratory pathogens promise to be especially costly for health care
      organizations to implement. Little data exist to show that the quality of
      infection control has been enhanced by these regulations. Standards are difficult
      to develop, because the science to back them up often is lacking, interpretation
      of validating data is imprecise, and inherent biological variation makes
      exceptions common. Seven lessons are important for those developing standards
      today. These include focusing on objective measures of the impact of the
      standard, clearly indicating the degree of scientific validity, making the
      development process inclusive, allowing for local variation, making sure that
      funding is provided for mandated standards, considering non-scientific
      implications of standards, and remaining involved in the process after the
      guideline is developed. Infection control workers should make sure that standards
      developed take the lessons above into account before they are promulgated.

PMID- 7561001
TI  - Compliance with handwashing and barrier precautions.
AB  - Compliance with handwashing and barrier precautions remains suboptimal in all
      health care settings and among all types of staff. Interventions to increase
      compliance include educational and motivational programmes, providing individual
      and group feedback on performance, modifying and improving equipment available,
      changing administrative policy and sanctions, and increasing staff commitment
      with role modelling. Single, isolated interventions are unlikely to meet with
      sustained success. A theory-based, multifaceted approach is indicated.

PMID- 7561002
TI  - Bibliography of the current world literature in hypertension.

PMID- 7561003
TI  - Glucose-induced vascular smooth muscle dysfunction: the role of protein kinase C.

PMID- 7561004
TI  - Angiotensin II and glomerulonephritis.

PMID- 7561005
TI  - Diurnal blood pressure variations and onset of subarachnoid haemorrhage: a
      population-based study.
AB  - OBJECTIVES: To analyse the association between time of onset of subarachnoid
      haemorrhage and diurnal blood pressure variations of ambulant normo- and
      hypertensive subjects. DESIGN: Retrospective, population-based study. SETTING:
      The population (246,000) of the Health Care District of Central Finland.
      PATIENTS: During 1980-1987 a total of 332 subjects in the study population had
      their first subarachnoid haemorrhage. The hour of onset could be obtained for 287
      patients, and these form the basis of the present study. RESULTS: The onset of
      subarachnoid haemorrhage occurred significantly more often during the waking
      hours than during the night. The correlation between the hourly numbers of
      patients suffering a haemorrhage and the corresponding mean systolic and
      diastolic blood pressure values of ambulant normo- and hypertensive subjects was
      highly significant (r = 0.88, P < 0.001). The results were similar when the 224
      patients with proved aneurysmal bleed were analysed separately (r = 0.79-0.85, P
      < 0.001). CONCLUSIONS: The diurnal blood pressure variations of ambulant normo-
      and hypertensive subjects, especially the transient blood pressure peaks reaching
      much higher levels of pressure during the waking hours than during the night, may
      be crucial in determining the time of rupture of a critically weakened aneurysm
      wall.

PMID- 7561006
TI  - The importance of adrenaline, insulin and insulin sensitivity as determinants for
      blood pressure in young Danes.
AB  - OBJECTIVE: To study the influence of the adrenergic system, fasting serum insulin
      level and insulin sensitivity on systolic (SBP) and diastolic blood pressure
      (DBP) in young individuals. DESIGN AND METHODS: In a population survey we
      measured SBP and DBP (using the London School of Hygiene sphygmomanometer) and
      fasting levels of serum catecholamines, serum insulin and insulin sensitivity in
      383 randomly recruited subjects (mean age 25.0 years) of both sexes. Insulin
      sensitivity was estimated from a combined intravenous glucose and tolbutamide
      tolerance test and calculated using Bergman's minimal model. Confounders were
      body mass index, waist:hip ratio, maximal aerobic capacity, age, sex, and
      consumptions of tobacco and alcohol. RESULTS: In a multiple regression analysis
      including the above factors, the most important determinant of SBP, after sex,
      was the plasma adrenaline level (partial correlation coefficient, rp = 0.23, P <
      0.01). No significant association was found between plasma noradrenaline level
      and SBP. A significant association was found between plasma adrenaline level and
      DBP in females only (rp = 0.15, P < 0.05). Overall, the plasma adrenaline level
      was more important than the plasma noradrenaline level. Fasting serum insulin
      level and insulin sensitivity were each significantly correlated with both SBP
      and DBP in univariate analyses, but not in a multiple regression analysis. A
      family history of hypertension was associated with higher SBP level, body mass
      index and fasting serum insulin level, and with lower insulin sensitivity, but
      with no difference in circulating plasma adrenaline or noradrenaline compared
      with individuals without a family history. In a multiple regression analysis with
      the above confounders, no significant association between SBP and plasma
      adrenaline level could be found in either sex for subjects with a family history
      of hypertension. Both male (rp = 0.41, P < 0.001) and female (rp = 0.18, P <
      0.05) subjects with no history of family hypertension had a significant
      association between SBP and plasma adrenaline level in a multiple regression
      analysis. CONCLUSION: In young healthy Caucasians adrenergic activity is an
      important determinant for SBP. The importance of fasting serum insulin level and
      insulin sensitivity on blood pressure level is minor when confounders are
      considered.

PMID- 7561007
TI  - Alterations in beta-adrenoceptors and polyploidy in cultured aortic smooth muscle
      cells from different age groups of spontaneously hypertensive rats and Wistar
      Kyoto rats.
AB  - OBJECTIVE: The relationship between the number of beta-adrenoceptors and
      polyploidy in cultured aortic smooth muscle cells derived from different age
      groups of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto
      (WKY) rats were examined. DESIGN: The number of beta-adrenoceptors, the
      percentage of multinucleated cells and the incidence of polyploidy from cultured
      smooth muscle cells derived from SHR and WKY rats aged 3-4, 10-12 and 28-30 weeks
      were measured. The effect of passaging of the cells on the expression of beta
      adrenoceptors and polyploidy on cultured smooth muscle cells from both SHR and
      WKY rats was also investigated. METHODS: Receptor binding experiments were
      carried out using [125]-monoiodocyanopindolol with osmotically lysed cultured
      aortic smooth muscle cells to investigate the properties of vascular beta
      adrenoceptors in SHR and WKY rats. The proportion of polyploid smooth muscle
      cells was determined by frequency distribution analyses of Feulgen DNA
      microdensitometric measurements. RESULTS: The incidence of polyploid smooth
      muscle cells was consistently higher in cells cultured from SHR than in those
      from WKY rats in all three age groups, with a positive correlation between
      polyploidy and age in SHR. Furthermore, in all three age groups the number of
      beta-adrenoceptor binding sites was also higher in cultured smooth muscle cells
      from SHR than in those from WKY rats. There was no significant difference in the
      receptor affinity. The increase in beta-adrenoceptor number was associated with
      an increase in polyploidy, and both of these changes were positively correlated
      both with the age of the rats from which these cells were derived and with the
      number of passages. CONCLUSIONS: Under cell culture conditions the expression of
      beta-adrenoceptor density increases with the number of passages in both SHR and
      WKY rats. Smooth muscle cells derived from older SHR and WKY rats have a greater
      propensity to develop polyploidy. This trend is significantly accelerated in
      cultured smooth muscle cells derived from SHR compared with those from WKY rats,
      suggesting a premature ageing process. These findings suggest that, in cultured
      smooth muscle cells from SHR and WKY rats, beta-adrenoceptors may influence the
      expression of polyploidy.

PMID- 7561009
TI  - The regulation of pH in resistance arteries from spontaneously hypertensive and
      Wistar-Kyoto rats: the effect of bicarbonate.
AB  - OBJECTIVE: To assess intracellular pH regulation in the presence of bicarbonate
      in resistance arteries from spontaneously hypertensive rats and Wistar-Kyoto
      (WKY) rats. METHODS: Intracellular pH was determined in isolated resistance
      arteries from male adults SHR and WKY rats with the pH-sensitive fluorescent dye
      bis-carboxyethyl carboxyfluorescein, while the arteries were mounted in a
      myograph for simultaneous measurements of force. The arteries were acid-loaded
      using the ammonium chloride technique and the recovery from the acidosis was
      determined in resting arteries and in arteries activated with 50 mmol/l potassium
      or arginine vasopressin. This protocol was performed in the presence and in the
      absence of bicarbonate. RESULTS: In the absence of bicarbonate the intracellular
      pH was higher in resting arteries from SHR than in those from WKY rats, whereas
      during activation no significant difference was found. In the presence of
      bicarbonate no difference in intracellular pH between arteries from SHR and WKY
      rats could be found. The addition and washout of 15 mmol/l ammonium chloride were
      associated with large force transients in activated arteries both from SHR and
      from WKY rats. The proton recovery rate at intracellular pH 6.85 in the absence
      of bicarbonate was higher in activated arteries from SHR than in those from WKY
      rats, whereas in resting arteries no significant difference was found. In the
      presence of bicarbonate no significant difference between SHR and WKY rat
      arteries was found. CONCLUSION: In the presence of bicarbonate a possible
      abnormality of the sodium-hydrogen exchange in resistance arteries from SHR is
      not manifested, because regulation of intracellular pH by bicarbonate-dependent
      mechanisms can compensate for such an abnormality.

PMID- 7561008
TI  - Dietary sodium and Na,K-ATPase activity in Dahl salt-sensitive versus salt
      resistant rats.
AB  - OBJECTIVE: To investigate the effects of high dietary sodium on brain and kidney
      Na,K-ATPase activity in Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R)
      rats. METHODS: From the age of 4 weeks Dahl-S and Dahl-R rats were fed either
      standard or high-sodium diet (8% sodium chloride) for 3 weeks. The hydrolysis of
      [gamma-32P]-ATP in the absence or presence of various concentrations of ouabain
      was used to determine apparent Na,K-ATPase activity and its isoform composition.
      To assess whether reduced Na,K-ATPase activity and its isoform composition. To
      assess whether reduced Na,K-ATPase activity was caused by an endogenous
      inhibitor, brain and kidney microsomes were pre-incubated with antibody Fab
      fragments (Digibind). RESULTS: The high-sodium diet increased mean arterial
      pressure in the Dahl-S but not in the Dahl-R rats. Two binding sites (alpha 1 and
      alpha 2) in several areas of the brain and one binding site in the kidneys (alpha
      1) were detected. The high-sodium diet reduced Na,K-ATPase activity in the
      hypothalamus of the Dahl-S but not of the Dahl-R rats, but did not cause changes
      in the brain cortex, pons or kidney. The Na,K-ATPase isoform composition in the
      brain cortex, hypothalamus and pons and kidney was not changed by the high-sodium
      diet. In the rats fed the standard-sodium diet, Digibind increased Na,K-ATPase
      activity only in the hypothalamus of the Dahl-S rats. In rats fed the high-sodium
      diet, Na,K-ATPase activity was increased by Digibind in the hypothalamus of both
      strains of rats, but by more in the Dahl-S rats. CONCLUSION: The present data
      indicate that a high-sodium diet inhibits hypothalamic Na,K-ATPase via increased
      binding of an inhibitor.

PMID- 7561010
TI  - Vascular albumin permeability and hypertrophy in a rat model combining
      streptozotocin-induced diabetes and genetic hypertension.
AB  - OBJECTIVE: To investigate the effects of hypertension and diabetes mellitus on
      vascular albumin permeability and hypertrophy in 11-week-old Wistar-Kyoto (WKY)
      rats and spontaneously hypertensive rats (SHR) with and without 3 weeks of
      streptozotocin-induced diabetes. METHODS: Vascular albumin permeability was
      measured as tissue content of intravenously injected Evans blue dye. RESULTS:
      Diabetic rats showed hypertrophy of the kidneys, and hypertensive rats showed
      hypertrophy of the heart. In the mesenteric artery there was an additive
      hypertrophic effect of diabetes and hypertension. The Evans blue content in
      kidneys was higher in diabetic SHR than in diabetic and in control WKY rats. The
      kidney: plasma Evans blue ratio was higher in diabetic SHR than in the other
      three groups, and the heart: plasma Evans blue ratio was higher in diabetic SHR
      than in control WKY rats or control SHR. The Evans blue content and tissue:
      plasma Evans blue ratio did not differ in aorta, mesenteric artery or skeletal
      muscle among the groups. There was no positive correlation between vascular
      albumin permeability and hypertrophy in any of the tissues studied. CONCLUSION:
      There was no relationship between vascular albumin permeability and hypertrophy,
      but increased vascular albumin permeability was found in kidneys and hearts of
      rats with both diabetes and hypertension. This suggests an additive or
      synergistic effect of diabetes and hypertension in producing vascular changes.

PMID- 7561011
TI  - Effect of one-kidney, one clip hypertension on the structure and function of
      porcine intramyocardial small arteries.
AB  - OBJECTIVE: To determine the influence of experimental hypertension on the
      structure and function of porcine coronary small arteries. METHODS: Miniature
      pigs underwent partial left renal artery constriction and contralateral
      nephrectomy. Blood pressures were recorded, using indwelling carotid artery
      catheters. After 4 weeks the pigs were killed, the heart was removed and
      subepicardial third-order branches of the left anterior descending artery were
      dissected and mounted in a myograph for morphological and functional assessment.
      RESULTS: Final mean +/- SEM systolic and diastolic blood pressures were,
      respectively, 197 +/- 9 and 142 +/- 7 mmHg (n = 21) for the hypertensive pigs and
      125 +/- 4 and 80 +/- 4 mmHg (n = 11) for the sham-operated control pigs.
      Hypertension was associated with significant left ventricular hypertrophy. The
      media thickness: lumen diameter ratio was increased significantly in hypertensive
      intramyocardial small arteries, caused mainly by remodelling (remodelling index
      92%) rather than by medial growth. Maximal contractile responses to potassium and
      acetycholine were significantly depressed in the arteries from hypertensive pigs,
      whereas endothelium-dependent relaxation responses to bradykinin, substance P and
      serotonin were not significantly influenced by hypertension. CONCLUSIONS: These
      results demonstrate that even short-term hypertension induces both structural and
      functional changes in left ventricular intramyocardial small arteries.

PMID- 7561012
TI  - Effect of intravenous calcium antagonists on left ventricular diastolic function
      in hypertension: assessed by pulsed-Doppler echocardiogram.
AB  - OBJECTIVE: To investigate the acute effects of the calcium antagonists
      nicardipine and diltiazem on blood pressure and left ventricular diastolic
      filling in hypertensive patients. DESIGN: Transmitral flow velocities were
      measured by pulsed-Doppler echocardiography before and during infusion of
      nicardipine (1, 2 and 3 micrograms/kg per min) and diltiazem (5, 10 and 15
      micrograms/kg per min) in seven patients with essential hypertension. Arterial
      pressure was measured directly, and other haemodynamic indices were obtained
      using a right-sided heart catheter. RESULTS: The calcium antagonists
      significantly decreased blood pressure and total peripheral resistance. Changes
      in mean blood pressure correlated with those in total peripheral resistance.
      Heart rate was significantly increased by nicardipine but decreased by diltiazem.
      Nicardipine and diltiazem both increased significantly the peak early filling
      velocity and the peak velocities of early: late filling ratio. The changes in the
      ratio correlated inversely with those in total peripheral resistance. CONCLUSION:
      Intravenous infusion of nicardipine or diltiazem causes a fall in blood pressure
      by decreasing total peripheral resistance, with beneficial effects on left
      ventricular diastolic filling that are independent of changes in heart rate in
      patients with hypertension.

PMID- 7561013
TI  - Left ventricular mass in hereditary human hypertension: glucocorticoid
      suppressible hyperaldosteronism.
AB  - BACKGROUND: The mineralocorticoid hormone aldosterone may be an important
      mediator of pathological ventricular hypertrophy and heart failure. Much of the
      evidence for this arises from experimental work in rat models of
      mineralocorticoid-dependent hypertension, and a pathological role in humans is
      still uncertain. SUBJECTS: Eleven subjects with glucocorticoid-suppressible
      hyperaldosteronism, a hereditary form of hyperaldosteronism and hypertension, and
      10 age- and sex-matched control subjects were studied. RESULTS: The subjects with
      glucocorticoid-suppressible hyperaldosteronism had a higher mean blood pressure
      and plasma aldosterone concentration, and lower plasma renin concentration, than
      the control subjects. Left ventricular mass index was not significantly different
      in the subjects with glucocorticoid-suppressible hyperaldosteronism than in the
      control subjects. When the subjects with glucocorticoid-suppressible
      hyperaldosteronism were subdivided into those with and those without
      hypertension, no difference in left ventricular mass index could be detected
      between the subgroups or between either subgroup and the control subjects.
      However, there was a significant correlation between basal plasma aldosterone and
      left ventricular mass index in the subjects with glucocorticoid-suppressible
      hyperaldosteronism (r = 0.66, P < 0.03). CONCLUSIONS: Despite marked elevations
      in plasma aldosterone concentrations from birth in subjects with glucocorticoid
      suppressible hyperaldosteronism, left ventricular hypertrophy did not occur. The
      degree of hyperaldosteronism in the subjects was mild compared with other
      conditions and, although an effect on left ventricular mass index could be
      detected, the present results indicate that other factors may be necessary for
      the development of left ventricular hypertrophy.

PMID- 7561014
TI  - Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid
      in the reversal of one-kidney, one clip hypertension.
AB  - OBJECTIVE: To examine the role of changes in renal hemodynamics and P-450
      metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K,1C)
      hypertension in rats. DESIGN: The stimulus for the release of an antihypertensive
      lipid from the kidney is not known. This study examined whether cortical or
      papillary blood flow is altered after removal of the clip from the renal artery
      of 1-K,1C hypertensive rats, and the effects of blockade of the renal metabolism
      of arachidonic acid by P-450 with 17-octadecynoic acid (17-ODYA) on the fall in
      blood pressure. METHODS: Cortical and medullary blood flows were measured using
      laser-Doppler flowmetry. 17-ODYA (33 nmol/min) was infused directly into the
      renal artery to examine the effect of inhibition of renal P-450 activity on
      reversal of 1-K,1C hypertension. The renal metabolism of arachidonic acid in
      control and in 1-K,1C hypertensive rats was assessed by incubating microsomes
      with [14C]-arachidonic acid, the metabolites formed being measured using reverse
      phase high-performance liquid chromatography. The antihypertensive effects of
      these P-450 metabolites of arachidonic acid were compared with those of
      medullipin I after intravenous administration in conscious spontaneously
      hypertensive rats (SHR). RESULTS: Cortical and papillary blood flow increased
      significantly and arterial pressure fell after unclipping the renal artery in the
      1-K,1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after
      unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was
      elevated in microsomes prepared from the renal cortex of the 1-K,1C hypertensive
      rats. However, intravenous administration of these metabolites did not mimic the
      effect of medullipin I to lower arterial pressure in SHR. CONCLUSION: Elevations
      in renal cortical or papillary blood flow, or both, may stimulate the release of
      a P-450-derived antihypertensive lipid from the kidney after unclipping of the
      renal artery in 1-K,1C hypertensive rats. However, it is unlikely that this
      substance is a P-450 metabolite of arachidonic acid.

PMID- 7561015
TI  - Repetitive gene mapping.

PMID- 7561016
TI  - Is blood pressure treatment as effective in a population setting as in controlled
      trials? Results from a prospective study.

PMID- 7561017
TI  - A new potential contributor to circadian sympathetic variations.

PMID- 7561018
TI  - Antigen and Fc receptor signaling. The awesome power of the immunoreceptor
      tyrosine-based activation motif (ITAM).

PMID- 7561019
TI  - Structure of human phagocyte cytochrome b and its relationship to microbicidal
      superoxide production.

PMID- 7561021
TI  - Migration of dendritic cells in response to formyl peptides, C5a, and a distinct
      set of chemokines.
AB  - Trafficking to tissues and then to lymph nodes is a crucial aspect of the
      immunobiology of dendritic cells. The present study was designed to identify
      molecules able to direct the migration of human blood-derived dendritic cells.
      fMLP (representative of formyl peptides of bacterial origin), C5a, and the C-C
      chemokines monocyte chemotactic protein (MCP)-3, MIP-1 alpha/LD78, and RANTES
      elicited chemotactic migration and a rise of intracellular free calcium in
      dendritic cells. In contrast, the C-X-C chemokines IL-8 and IP-10 and the C-C
      chemokines MCP-1 and MCP-2 were inactive as chemoattractants. Thus, dendritic
      cells respond to classical chemotactic signals and to a set of chemokines
      distinct from that active on monocytes and neutrophils. Chemoattractants are
      likely to contribute to localization and trafficking of dendritic cells and
      provide tools to recruit these cells in the design of immunization strategies.

PMID- 7561020
TI  - Regulation of apoptosis in neutrophils--Fas track to death?

PMID- 7561022
TI  - Differential activation of a calcium-dependent endonuclease in human B
      lymphocytes. Role in ionomycin-induced apoptosis.
AB  - The state of B cell maturation profoundly influences the outcome, i.e.,
      activation, growth arrest, or programmed cell death, of a variety of stimuli,
      including the calcium ionophore, ionomycin. Initial studies confirmed the
      observation that cell lines representative of immature B cells, i.e., Burkitt
      lymphoma cell lines, were induced to undergo apoptosis in response to ionomycin,
      whereas more mature B cell lines did not, and instead underwent cell cycle arrest
      in the G1 interval. To understand this differential outcome, we have focused on
      comparing the expression and activation of an endonuclease(s) in cells induced by
      ionomycin to undergo programmed cell death (Ramos) with cells resistant to
      ionomycin-induced programmed cell death (Ly1). Our results demonstrated that a
      low m.w. fraction of an endogenous Ca2+/Mg(2+)-dependent endonuclease was
      activated in Ramos cells, but not in activated Ly1 cells, following the addition
      of ionomycin. Of interest, however, low m.w. endogenous endonuclease(s) activity
      was induced when isolated Ly1 cell nuclei were treated with exogenous calcium
      instead. Use of field inversion gel electrophoresis further indicated that
      cleavage of DNA into large m.w. (> 50 kbp) DNA fragments does not precede
      ionomycin-induced internucleosomal cleavage in Ramos cells or in ionomycin
      resistant Ly1 cells. In summary, these data support the conclusion that ionomycin
      induced apoptosis involves the activation of a latent, low m.w., calcium
      responsive endonuclease and suggest that control of endonuclease depression may
      contribute to cell-specific regulation of calcium ionophore-induced apoptosis.

PMID- 7561023
TI  - Incomplete T cell receptor V beta allelic exclusion and dual V beta-expressing
      cells.
AB  - Recent studies have documented incomplete TCR V alpha-chain allelic exclusion and
      dual V alpha-bearing T cells. Herein, we show that V beta allelic exclusion is
      also incomplete, since a significant proportion of peripheral T cells express
      dual V beta in both TCR transgenic and normal mice. Studies in TCR transgenic
      mice indicated that although a small proportion of T cells escaped allelic
      exclusion in the thymus, dual V beta-expressing cells expanded dramatically in
      the periphery with age, and such expanded cells had an activated phenotype.
      Although not as pronounced, age-related increases in dual V beta-bearing cells
      were also observed in normal mice. These findings may have important implications
      for TCR selection and specificity, age-related repertoire changes, and autoimmune
      disease pathogenesis.

PMID- 7561024
TI  - Exogenous hepatitis B surface antigen particles processed by dendritic cells or
      macrophages prime murine MHC class I-restricted cytotoxic T lymphocytes in vivo.
AB  - Injection of low doses of particulate hepatitis B surface Ag (HBsAg) into H-2d
      mice without adjuvants primes an Ld-restricted, S28-39-specific T cell response.
      This study indicates that dendritic cells (DC) and macrophages (M phi) both serve
      as APCs that support priming of CD8+ CTL precursors in vivo to exogenous HBsAg
      particles. After transfer into a syngeneic, naive host, HBsAg particle-pulsed DC,
      either freshly purified from skin or derived from a cloned DC line, efficiently
      primed class I-restricted, HBsAg-specific CTL precursors. M phi, either harvested
      from the peritoneal cavity or generated in macrophage-CSF-stimulated bone marrow
      cell cultures in vitro or derived from established, cloned M phi lines (PU5-1.8,
      J774A.1), pulsed with HBsAg particles in vivo or in vitro, elicited a class I
      restricted, HBsAg-specific CTL response after adoptive transfer into naive hosts.
      The class I-restricted CTL response induced by HBsAg particle immunization was
      suppressed in carrageenan-treated mice, but was restored when carrageenan-treated
      mice were immunized with syngeneic, HBsAg-pulsed M phi. Selective elimination of
      M phi by liposome-incorporated dichloromethylene-diphosphonat did not suppress
      the induction of a CTL response of H-2d mice by HBsAg particle immunization.
      HBsAg-pulsed, freshly prepared DC are more potent than pulsed M phi in priming
      class I-restricted CTL in vivo. The relative importance of both types of APC in
      priming CTL remains to be resolved.

PMID- 7561025
TI  - Regulation by corticosteroids of Th1 and Th2 cytokine production in human CD4+
      effector T cells generated from CD45RO- and CD45RO+ subsets.
AB  - Corticosteroids (CS) are widely used as immunosuppressive and anti-inflammatory
      agents, but their mechanism of action is not well understood. In this study we
      analyzed the effects of CS on the growth and differentiation of human CD4+45RO-
      "naive" and CD4+45RO+ "memory" T cells. To generate effector T cells secreting
      large amounts of Th1 and Th2 cytokines, FACS-sorted naive and memory subsets were
      primed and restimulated in vitro via the TCR in the presence of IL-2. CS added
      during priming reduced clonal expansion of both T cell populations, but the
      memory subset was 100-fold less sensitive. At lower concentrations, CS favored
      the development of effector T cells (from both subsets), which upon restimulation
      produced large amounts of the anti-inflammatory cytokine IL-10, but low amounts
      of IL-4, IL-5, or IFN-gamma. Interestingly, CS displayed different effects if it
      was added only during the restimulation of effector T cells. CS were unable to
      suppress clonal expansion of restimulated effector T cells. In effector T cells
      derived from the naive subset, CS induced production of IL-4 and IL-10, but
      blocked production of IL-5 and IFN-gamma. In effector T cells generated from the
      memory subset, CS blocked production of IL-4, IL-5, and IL-10, but inhibited
      production of IFN-gamma by only 50%, even if 100-fold higher concentrations of CS
      were applied. These results indicate that persistent TCR stimulation, e.g., in
      chronic infection, may reduce the sensitivity of T cells to the antiproliferative
      effects of CS. Furthermore, the potential of CS to increase or suppress IL-4 and
      IL-10 production depending on the stage of T cell activation may explain in part
      the beneficial effects of CS in the treatment of acute inflammation and chronic
      allergic/asthmatic diseases.

PMID- 7561026
TI  - Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low
      density tonsillar B cells.
AB  - The regulation of B cell death plays roles in the selection of Ag-specific B
      cells in humoral immune responses, controlling B cell homeostasis and perhaps
      limiting transformation. The present work addresses whether CD95 induces
      tonsillar B cells to undergo apoptosis and, if so, whether contact-dependent CD40
      L:CD40 signaling can rescue tonsillar B cells from CD95-induced apoptosis. CD95
      triggering by anti-CD95 mAb (APO-1) was studied in human tonsillar B cell
      populations that were separated by density centrifugation into fractions enriched
      for either low density, CD38+ B cells or high density, resting B cells. Low
      density tonsillar B cells express CD95 and undergo anti-CD95-mediated apoptosis
      by analysis of cellular morphology or DNA fragmentation by TUNEL assay. The
      induction of apoptosis in low density tonsillar B cells by anti-CD95 mAb is
      inhibited by CD40 signals provided by stably transfected CD40-L+ 293 cells, but
      not by control transfected 293 cells (expressing CD8). In addition, the rescuing
      effect of CD40-L+ cells is inhibited specifically by anti-CD40-L (mAb 5c8). The
      counteracting effects of CD95 and CD40 signaling were also studied in Ramos 2G6,
      a homogeneous B cell tumor line of germinal center phenotype that expresses CD95
      and CD40. Similar to the behavior of low density tonsillar B cells, Ramos 2G6
      undergoes anti-CD95-mediated apoptosis, which is prevented by CD40-mediated
      rescue. These data show that CD95 induces apoptosis in low density tonsillar B
      cells and that CD40-L:CD40 interactions rescue low density tonsillar B cells or
      the B cell tumor Ramos 2G6 from CD95-induced apoptosis, and suggest roles for
      CD95 and CD40 in B cell death and selection, respectively.

PMID- 7561027
TI  - Extrathymic maturation of alpha beta T cells from hemopoietic stem cells.
AB  - The object of the study was to determine whether alpha beta T cells can develop
      from hemopoietic stem cells in the absence of the thymus. C57BL/6 (Ly-5.1 and Thy
      1.2) mice were thymectomized or sham-thymectomized at 4 wk of age, and received
      lethal whole body irradiation 2 wk later. These mice were reconstituted with an
      i.v. injection of 500 highly purified hemopoietic stem cells (Mac-1-, B220-, TER
      119-, CD3-, CD4-, CD8-, Thy 1low, SCA-1+) obtained from the bone marrow of
      C57BL/6 (Ly-5.2 and Thy-1.1) donors. A similar percentage of Ly-5.2+ alpha beta T
      cells (donor) was found in the marrow of thymectomized recipients, sham
      thymectomized recipients, and normal donor mice at least 3 mo after stem cell
      transplantation. The percentage of Ly-5.2+ alpha beta T cells in the spleens of
      sham-thymectomized and normal donor mice was similar. The percentage in the
      spleens of thymectomized recipients was reduced by about 50%, and approximately
      one-half of the latter T cells expressed the CD4-CD8- alpha beta+ phenotype. A
      purified population of Ly-5.2+ alpha beta- cells obtained from the marrow of
      thymectomized recipients was incubated in vitro for 48 h without exogenous growth
      factors. After the incubation procedure a proportion of the marrow cells acquired
      alpha beta TCR surface receptors. The results show that alpha beta T cells can
      develop from hemopoietic stem cells in the absence of the thymus.

PMID- 7561028
TI  - Human follicular dendritic cells enhance cytokine-dependent growth and
      differentiation of CD40-activated B cells.
AB  - Germinal centers constitute microanatomic subunits within secondary follicles
      where B cells undergo somatic mutations, isotype switch and affinity selection.
      This allows the generation of memory B cells and plasma cells, whose Igs bind to
      the eliciting Ag with a high affinity. T cells and follicular dendritic cells
      (FDCs) are thought to play key roles in the germinal center reaction. To study
      effects of FDCs on B cell growth and differentiation, we have isolated FDC
      lymphocyte clusters from human tonsils by enzymatic digestion and centrifugation
      of the resulting cell suspension through BSA gradient. Irradiated FDC-lymphocyte
      clusters induced moderate proliferation of autologous B cells. IL-2 was the only
      cytokine able to enhance B cell proliferation cocultured with FDCs. When B cells
      were activated by soluble anti-CD40 Ab with or without IL-2, IL-3, IL-4, IL-10 or
      IL-13, addition of FDCs increased B cell proliferation. In the presence of FDCs,
      maximal B cell proliferation was observed in anti-CD40 stimulated cultures
      supplemented with either IL-4 + IL-10 or IL-2 + IL-10. Cultures performed in the
      presence of IL-2 and IL-10 resulted in high levels of Ig production in the
      presence of FDCs. In conclusion, the present study demonstrates that freshly
      isolated human FDCs can enhance the growth and differentiation of CD40-activated
      B cells.

PMID- 7561029
TI  - Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+ release in T
      lymphocyte cell lines.
AB  - Ca2+ release from intracellular stores is one of the major events transducing
      extracellular signals into living cells. Recently, a metabolite of nicotinamide
      adenine dinucleotide+ (NAD+), termed "cyclic adenosine diphosphate-ribose"
      (cADPr), has been described to release Ca2+ from caffeine-sensitive internal
      stores of cells. Jurkat T cells possess intracellular Ca2+ stores sensitive to
      caffeine, so a potential involvement of cADPr in Ca2+ signaling was investigated.
      cADPr released Ca2+ in a dose-dependent manner from intracellular stores of
      permeabilized Jurkat T cells. Half maximal release was obtained at 2.25 microM
      cADPr. Prior addition of D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or
      thapsigargin did not influence cADPr-induced Ca2+ release, indicating the
      presence of different Ca2+ pools sensitive to Ins(1,4,5)P3 and cADPr. The
      specificity of the response was confirmed using the inhibitors ruthenium red, 8
      NH2-cADPr, and 8-Br-cADPr. All three compounds blocked cADPr-induced, but not
      Ins(1,4,5)P3-induced, Ca2+ release in a dose-dependent manner. Cyclic GMP (cGMP)
      induced Ca2+ release was also partly antagonized by ruthenium red, indicating
      involvement of a cGMP-dependent step in the formation of cADPr. The presence of
      endogenous cADPr was analyzed directly by HPLC. Sequential separation on strong
      anion exchange HPLC and reverse-phase, ion-pair HPLC resulted in a single
      symmetric peak co-eluting with standard cADPr. The identity of this endogenous
      material was further confirmed by its ability to release Ca2+ in saponin
      permeabilized Jurkat T cells.

PMID- 7561030
TI  - Potential role of 4-1BB in T cell activation. Comparison with the costimulatory
      molecule CD28.
AB  - The expression of the murine T cell Ag 4-1BB, a member of the TNF-R family, is
      induced by T cell activation. Previously, we and others had shown that signaling
      through 4-1BB enhanced proliferative T cell responses. To investigate a potential
      role for the interaction of 4-1BB with its ligand (4-1BBL) in T cell activation,
      we studied the ability of a soluble chimera of 4-1BB (4-1BBFc) to interfere with
      proliferative responses and cytokine production in models of activation dependent
      in intercellular interactions. The potential blocking effect of 4-1BBFc was
      compared with that of the chimeric molecule CTLA-4Ig, a reagent known to
      interfere with the interaction of CD28 (and/or CTLA-4) with B7 costimulatory
      receptors. In this study, we report that 4-1BBFc partially blocked both the
      activation of unfractionated splenocytes triggered by soluble anti-CD3 (anti
      CD3s), and the more physiologically relevant responses to alloantigen. In
      addition, we show that both chimeric molecules partially blocked proliferative
      responses and IL-2 secretion by highly purified resting T cells activated with
      anti-CD3s in the presence of fixed accessory cells that express B7 receptors and
      4-1BBL. Furthermore, in this model system, the blocking capacity of 4-1BBFc and
      CTLA-4Ig appears to correlate with the relative expression of their respective
      cognate receptors (4-1BBL and B7) on the accessory cell. Simultaneous addition of
      both blocking reagents produced an additive effect in the model systems studied.

PMID- 7561031
TI  - Ig domains 1 and 2 of murine CD22 constitute the ligand-binding domain and bind
      multiple sialylated ligands expressed on B and T cells.
AB  - Baby hamster kidney cells transfected with murine CD22 (mCD22) mediate adhesion
      to B- and T-lineage cells. To further characterize mCD22-mediated cell adhesion,
      we generated a panel of recombinant globulins (Rg) consisting of different
      extracellular Ig-like (Ig) domains of mCD22. FACS analysis using these mCD22.Rgs
      revealed that ligands for mCD22 are expressed on both B and T cell lines and also
      normal B and T cells. In B-lineage cells, the expression of mCD22 ligands began
      on sIgM- pre-B cells in bone marrow. The ligand-binding site of mCD22 for ligands
      was mapped to Ig domains 1 and 2: mCD22.Rgs containing Ig domains 1 and 2 bound
      target cells and immunoprecipitated sets of glycoproteins similar to Rgs
      containing Ig domains 1 to 3 or all 7 CD22 Ig domains, whereas Rgs containing Ig
      domains 2 to 3 or 3 to 7 did not bind either B or T cells. Furthermore, B cells
      apparently expressed higher levels of mCD22 ligands than that of T cells,
      suggesting a potential competition for CD22 binding between ligands expressed on
      the same B cell and those expressed on another B cell or T cells.
      Immunoprecipitation experiments using the mCD22.Rgs identified mCD22 itself and
      the B cell-specific isoform of mCD45RA (B220) as two of the mCD22 ligands
      expressed on B cells. Thus, mCD22 may potentially regulate B cell activation
      through interactions with itself or mCD45RA/B220.

PMID- 7561032
TI  - Ig VH hypermutation is absent in the germinal centers of aged mice.
AB  - After injection with immunogenic conjugates of the hapten (4-hydroxy-3
      nitrophenyl)acetyl (NP), two distinct B cell populations can be identified in the
      spleen during the primary response. One of these populations is specialized for
      Ab production; the other, the germinal centers (GCs), has been identified as the
      site of Ig somatic hypermutation. Ag-driven selection of GC B cells bearing
      mutated receptors with higher affinity leads to the affinity maturation of serum
      Ab and increased protective humoral immunity. Microdissection of GC B cell
      populations specific for NP and sequencing of the recovered Ig heavy chain
      variable region genes revealed that the somatic hypermutation process is absent
      in the GCs of aged C57BL/6 mice. However, selection for Ag appears to occur in
      the absence of hypermutation in the form of competition between unmutated clones
      of Ag-activated B lymphocytes. Thus, affinity maturation in these animals is
      limited to the affinities of Ab encoded by the germline.

PMID- 7561033
TI  - Human B cell activation. Effect of T cell cytokines on the physicochemical
      binding requirements for achieving cell cycle progression via the membrane IgM
      signaling pathway.
AB  - Given the range of mIg-binding affinities expressed by Ag-specific B cells, the
      ligand:receptor affinity threshold for achieving full B cell activation via the
      mIgM-mediated signaling pathway is quite high. Several recombinant, or semi
      purified, cytokines were found to reduce the very high mIgM:ligand affinity
      threshold for induction of human B cell S phase entry by bivalent, affinity
      diverse anti-IgM mAbs without notably affecting the lower affinity threshold for
      G1-related RNA synthesis. Two-stage culture experiments suggested that one major
      means by which IL-4, IL-2, and low m.w. B cell growth factor lower the affinity
      threshold for S phase entry is an indirect one, i.e., rescue of B cells whose mIg
      engagements with Ag are of sufficient affinity for achieving G1 entry, but of
      insufficient affinity for initiating the late-phase mIgM-mediated signals needed
      for the G1-->S phase transition. IL-4 had additional effects in early G1. In
      contrast to the above cytokines, IFN-gamma, did not function as an independent
      cell cycle progression factor, but rather required the concomitant presence of
      mIgM-cross-linking ligand for enhancement. A greater potential of multivalent
      anti-IgM-dextran conjugates to trigger S phase entry in the absence of cytokines
      was found to reflect a greater potential for initiating mIgM signals during the
      late phase in B cell activation. The results indicate that progression of mIgM
      receptor-activated B cells past a G1-->S phase restriction point is dependent
      upon continued signal transduction via either the mIgM receptor and/or a cytokine
      receptor signaling pathway. When mIgM-engaging ligands are ineffective at
      initiating late-phase signals, due to limited size and binding site valency
      and/or affinity, ancillary signal transduction through cytokine receptors becomes
      most relevant.

PMID- 7561034
TI  - Control of the IL-2 responsiveness of B lymphocytes by IL-2 and IL-4.
AB  - A two-step culture system was used to analyze the parameters involved in the
      acquisition of IL-2 responsiveness by murine B cells. In the first culture,
      unstimulated, or resting, B cells prepared from spleen of naive animals were
      challenged during 48 h with IL-2, IL-4, anti-mu, anti-mu+IL-2, anti-mu+IL4, or
      anti-mu+IL-2 + IL-4. In a second culture, IL-2 responsiveness was followed by
      measuring either the cell proliferation or the Ig production. It was found that
      only B cells stimulated by anti-mu+IL-2 were able to respond. The expression of
      three chains of the IL-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma) was
      studied by FACS. IL-2R beta and IL-2R gamma were found to be expressed
      constitutively on resting B cells. IL-2R alpha was induced by anti-mu and anti
      mu+IL-2 treatment. Although B cells treated by anti-mu alone are not able to
      respond to IL-2, they do express an IL-2 binding capacity comparable with B cells
      treated by anti-mu+IL-2. This paradoxical result suggests that IL-2 has a direct
      influence on the acquisition of the IL-2 responsiveness. IL-4 exerts a negative
      effect on the IL-2 response. At the molecular level, IL-4 was found to reduce
      selectively the IL-2R beta expression at the B cell surface. This effect was
      confirmed by Northern blot analysis. Maximum expression of the IL-2R beta mRNA is
      obtained after anti-mu+IL-2 treatment. In the presence of IL-4, expression of the
      IL-2R beta mRNA is greatly reduced.

PMID- 7561035
TI  - Estrogen suppresses stromal cell-dependent lymphopoiesis in culture.
AB  - Numbers of pre-B cells change dramatically and reciprocally in response to
      estrogen levels in mice, suggesting that normal lymphopoiesis may be under
      hormonal control. However, little is known of the mechanisms involved in this
      process. We found that estrogen receptor mRNA was detectable by RT-PCR in
      lymphocyte supporting stromal cells as well as B lymphocyte precursors. Unlike
      glucocorticoids, estrogen did not induce apoptosis in isolated B lineage
      lymphocytes or interfere with their responsiveness to IL-7 in semisolid agar.
      Estrogen did inhibit clonal expansion of B cell precursors in a limiting dilution
      type assay when the lymphocytes were cultured on a stromal cell clone. In other
      experiments, B cell precursors at particular stages of differentiation were
      isolated by cell sorting and cocultured with stromal cells for 4 days. This
      revealed that some subsets were more sensitive to an estrogen-containing
      environment than others. Although numbers of recovered cells were greatly
      reduced, the remaining lymphocytes had undergone relatively normal
      differentiation. The surviving population was enriched in cells that had acquired
      cytoplasmic mu chains, BP-1 Ag, and clonability with IL-7. Hormone-mediated
      inhibition occurred in serum and phenol-red free medium, and in cultures replete
      with IL-7. Direct contact between stromal cells and lymphocytes was not required.
      Furthermore, suppression resulted when stromal cells alone were treated with the
      hormone. These findings indicate that estrogen may regulate B lymphopoiesis via
      its influence on the microenvironment and that estrogen-induced stromal cell
      genes merit further study.

PMID- 7561036
TI  - Rapamycin inhibits ribosomal protein synthesis and induces G1 prolongation in
      mitogen-activated T lymphocytes.
AB  - We investigated the effects of rapamycin (RAP) on cell cycle progression and
      protein synthesis in mitogen-activated primary T lymphocytes. Stimulation of
      resting human T lymphocytes with phorbol ester and calcium ionophore rendered
      cells capable of initiating DNA synthesis within 30 h; roughly 60% of the cells
      entered the first G2/M phase of the cell cycle within 96 h. Addition of RAP
      delayed the entry into S phase by 9 h, although a similar percentage
      (approximately 50%) of cells entered the first G2/M phase and proliferated. On
      this basis, we concluded that RAP primarily induced a G1 prolongation without
      blocking cell cycle progression. Addition of the co-mitogens to resting T
      lymphocytes up-regulated the translation of ribosomal protein mRNA concurrent
      with activation of p70s6k. RAP inhibited this translational up-regulation of
      ribosomal protein mRNA as well as the activation of p70s6k without affecting
      translation of nonribosomal protein mRNA. RAP also prevented the synthesis and
      accumulation of ribosomal proteins. Further, this failure to increase ribosomal
      proteins, which probably reflects the failure to increase numbers of ribosomes,
      resulted in suppression of the synthesis of total cellular protein and a delay in
      the escalation of cell size. RAP-treated cells eventually initiated DNA synthesis
      when cell size became equivalent to that of the control cells entering S phase of
      the cell cycle. Thus, inhibition of protein synthesis caused by the primary
      inhibition of ribosomal protein mRNA translation probably explains the effect of
      RAP on cell cycle progression of mitogen-activated resting T lymphocytes.

PMID- 7561037
TI  - Secondary response to Listeria infection requires IFN-gamma but is partially
      independent of IL-12.
AB  - During a secondary immune response to Listeria monocytogenes (LM), the production
      of IFN-gamma was still required for resistance, but it was considerably less
      dependent on IL-12 production. When IL-12 was neutralized in vivo using specific
      hamster antimurine IL-12 mAbs, there was a dramatically increased susceptibility
      to infection during primary listeriosis but much less during a secondary
      infection. However, neutralization of IFN-gamma in vivo resulted in a similar
      increased susceptibility during both primary and secondary listeriosis. In
      culture, splenocytes isolated from unimmunized mice produced IFN-gamma in
      response to heat-killed L. monocytogenes (hk-LM) that was absolutely dependent
      upon IL-12 production. However, directly stimulating the TCR with anti-CD3
      epsilon mAbs resulted in IFN-gamma production that was unaffected by neutralizing
      IL-12 in vitro. In contrast, splenocytes isolated from LM-immune mice produced
      IFN-gamma in response to hk-LM, part of which was independent on IL-12
      production. However, anti-CD3-epsilon Ab-stimulated IFN-gamma production remained
      independent of IL-12 production. The source of hk-LM-induced, IL-12-independent
      IFN-gamma production was the T cell because anti-Thy1.2 Ab plus complement
      treatment in vitro completely abolished it. Together, these data support a model
      of memory T cells being produced during the primary infection with LM that can be
      stimulated to produce IFN-gamma during the secondary response to LM, partially
      independent of macrophage IL-12 production.

PMID- 7561038
TI  - IL-1 beta converting enzyme (ICE) is not required for apoptosis induced by
      lymphokine deprivation in an IL-2-dependent T cell line.
AB  - Clonal T cells undergo programmed cell death (PCD) or apoptosis when cultured
      without the appropriate cytokines. The cysteine protease, IL-1 beta converting
      enzyme (ICE), is implicated in apoptosis based on its structural similarity to
      the PCD gene, ced-3, in Caenorhabditis elegans and the induction of PCD in
      fibroblasts transfected with recombinant ICE. We show that the murine IL-2
      dependent CTLL T cell line expresses ICE but not IL-1 beta. Interestingly, ICE
      mRNA and protein levels increase during apoptosis. Yet inhibition of ICE
      enzymatic activity (> 90%) with either of two cell-permeable ICE inhibitors does
      not abrogate or delay apoptosis following IL-2 deprivation, as measured by DNA
      fragmentation and viability. Our results suggest that ICE is not required for
      apoptosis in lymphokine-deprived T cells.

PMID- 7561039
TI  - Distinct phenotypes of antigen-selected CD8 T cells emerge at different stages of
      an in vivo immune response.
AB  - We have previously described a unique system for identifying Ag-selected CD8 T
      cells during an in vivo response in normal mice. In this system, lymphocytes
      isolated from DBA/2 mice injected i.p. with HLA-CW3 transfected syngeneic (H-2d)
      P815 cells show a remarkable expansion of CD8 cells that utilize TCR expressing
      the V beta 10 gene segment and additional structural features characteristic of
      Kd-restricted CW3-specific CTL clones. We have now taken advantage of this system
      to characterize the surface phenotype of CD8 cells selected by Ag in vivo. We
      observed several distinct phenotypes at different stages of the response. At the
      peak of the response, Ag-selected cells were low in CD62L and CD45RB expression
      but displayed high levels of CD44. In addition, there was a partial down
      regulation of CD8 and TCR. Cells of this phenotype were present in lymphoid
      tissues for several mo after immunization. Much later in the response, Ag
      selected cells expressed higher levels of CD8 and TCR. Moreover, a distinct
      subset of these long-term immune cells emerged that now expressed CD62L and
      CD45RB. Analysis of CD8 cells from different tissues also revealed certain
      differences, particularly in TCR and co-receptor levels from liver-derived cells
      compared with circulating cells at the peak of the response. Our findings suggest
      that the function of Ag-selected CD8 cells may be regulated over time and
      according to location by subtle changes in cell-surface phenotype.

PMID- 7561040
TI  - Radiation-induced apoptosis is differentially regulated in primary B cells from
      normal mice and mice with the CBA/N X-linked immunodeficiency.
AB  - Normal B cells responsive to thymus independent-type 1 Ags (TI-1) are resistant
      to low doses of ionizing radiation in vivo (200-300 cGy), compared with TI-1
      responsive B cells of mice with the CBA/N X-linked immunodeficiency (xid). This
      difference in radiosensitivity is an intrinsic B cell property; normal B cells
      adoptively transferred into xid mice remain TI-1-responsive after irradiation in
      situ. Because irradiation induces programmed cell death (PCD) in lymphocytes, we
      determined whether PCD were regulated differently in normal and xid B cells. B
      cells isolated immediately after irradiation from normal or xid donors when
      cultured without stimulators became apoptotic with the same kinetics and to the
      same extent, showing that apoptosis was induced equally in both populations.
      Apoptosis could be suppressed and mitogenesis could be induced frequently,
      however, if irradiated B cells were cultured with B cell activators. When
      activators using separate signal transduction pathways were compared, a hierarchy
      of efficiency at effecting apoptosis rescue was observed, and activators used
      singly without effect could synergize to protect. xid B cells were more resistant
      to rescue than normal B cells unless PMA was used as a stimulant. Although the
      mechanism of activator-induced rescue was not established, selective
      overexpression of a bcl-2 transgene rendered xid B cells radioresistant. The data
      suggest that a signal(s) delivered to irradiated B cells in the in vivo
      microenvironment suppresses apoptosis and that xid B cells and a radiosensitive
      subpopulation of normal B cells are refractory to this signal(s).

PMID- 7561041
TI  - Down-regulation of CD8 on mature antigen-reactive T cells as a mechanism of
      peripheral tolerance.
AB  - Previously we have shown that intravenous injection of male B6 lymphocytes
      containing CD8+ cells into B6 female anti-HY TCR transgenic mice results at 6 wk
      in the disappearance of the majority of male Ag-reactive T cells (TghighCD8+)
      from the periphery. Here we investigate the process in more detail. B6 female
      anti-HY TCR transgenic mice were intravenously injected with viable lymphocytes
      from male B6 normal, CD4-/-, CD8-/- or CD8-/- carrying a CD8 transgene lacking
      its cytoplasmic tail ("CD8 tail-less") mice. The fate of TghighCD8+ cells was
      followed in vivo. There was always a large (at least twofold) expansion of these
      cells in the periphery 4 days after encountering male Ag. Their subsequent fate
      differed, however, depending on whether or not the injected male lymphocytes
      contained normal CD8-expressing cells. If the injected male lymphocytes contained
      normal CD8 cells, at 6 wk there was a large drop in the number of TghighCD8+
      cells associated with a rise in the number of TghighCD8- cells. If the injected
      male lymphocytes lacked CD8 cells or expressed only tail-less CD8, TghighCD8+
      cell numbers returned to normal by 6 wk, while TghighCD8- cell numbers remained
      unchanged. The TghighCD8- cells, although carrying high levels of the male
      specific TCR, did not react to male Ag. In addition, their ability to respond in
      anti-CD3-induced activation, which does not require CD8 as a co-receptor, was
      significantly impaired. Our data suggest that down-regulation of CD8 on the Ag
      reactive T cells accounts, at least partially, for the disappearance of HY
      reactive T cells from the periphery. Further, some step in the process requires
      signaling through the cytoplasmic domain of CD8 on the injected Ag-bearing cells.

PMID- 7561042
TI  - IFN-gamma induces a p91/Stat1 alpha-related transcription factor with distinct
      activation and binding properties.
AB  - The 5' flanking region of the mig gene, a member of the chemokine family of small
      m.w. chemoattractant and growth regulatory factors, contains an IFN-gamma
      responsive enhancer, gamma RE-1, consisting of an extended imperfect palindrome.
      In this report we show that a novel factor, gamma RF-1, which binds to the gamma
      RE-1 element, is rapidly activated in a variety of primary cell types and tumor
      cell lines treated with IFN-gamma. Our data indicate that gamma RF-1 is present
      in a latent form in unstimulated cells and its DNA-binding activity is dependent
      upon tyrosine phosphorylation. UV cross-linking studies revealed that gamma RF-1
      consists of at least two proteins of approximately 95 and 130 kDa, which interact
      with the gamma RE-1 element. A comparison of gamma RF-1 and GAF, an IFN-gamma
      activated transcription factor containing the p91/Stat1 alpha protein (Stat,
      signal transducer and activator of transcription), showed that these two factors
      exhibited differences in electrophoretic mobility, responsiveness to IFN-alpha,
      and kinetics of activation. Using anti-Stat Ab, however, we found that one or
      more subunits of gamma RF-1 are antigenically related to p91/Stat1 alpha. Our
      results indicate, therefore, that gamma RF-1 and GAF are distinct IFN-gamma
      responsive transcription factors and probably contain closely related members of
      the Stat protein family.

PMID- 7561043
TI  - Polymorphism at position nine of the MHC class I heavy chain affects the
      stability of association with beta 2-microglobulin and presentation of a viral
      peptide.
AB  - To identify residues that control the interactions between MHC-heavy chains and
      (beta 2m) sequence comparisons were made between murine class I MHC molecules
      with high (H-2Dd, H-2Kb) and low (H-2Ld, H-2Db) affinities for beta 2m. A single
      residue at position 9 was evaluated for its contribution to the stability of the
      complex. Mutagenesis of the glutamic acid at position 9 of H-2Ld to valine, as is
      found in H-2Dd and H-2Kb, resulted in both qualitative and quantitative effects
      on inter-chain interactions, intracellular transport, peptide binding, and
      peptide presentation. In in vitro translation and assembly studies, the E9V
      mutation resulted in a more stable association of beta 2m with the heavy chain
      after immunoprecipitation with the alpha 2 domain-specific Ab 30-5-7 in the
      presence of an H-2Ld-restricted peptide. E9V variant expressed in transfected L
      cells had similar surface expression compared with H-2Ld despite exhibiting a
      slower rate of maturation. However, cells expressing E9V were unable to present
      peptide Ag to a specific T cell hybridoma. H-2LdE9V in E-3 cells, which are
      defective in TAP-dependent peptide transport, was expressed at higher levels than
      H-2Ld and was stabilized more efficiently by the addition of exogenous human beta
      2m. Thus, amino acid position 9 not only plays an important role in the
      interaction of the MHC-1 molecule with the beta 2m, it also qualitatively and
      quantitatively influences peptide binding and Ag presentation.

PMID- 7561044
TI  - Lethal shock is inducible by lipopolysaccharide but not by superantigen in mice
      with retrovirus-induced immunodeficiency syndrome.
AB  - The retrovirus-induced murine AIDS (MAIDS) shares many features with human AIDS.
      Here, we examined the susceptibility of mice with MAIDS to staphylococcal
      enterotoxin-triggered shock. Following sensitization with D-galactosamine (D
      Gal), mice with MAIDS were resistant to the otherwise lethal effect of
      superantigen staphylococcal enterotoxin A (SEA). Peak IL-2 levels in these mice
      after D-Gal/SEA challenge were 10-fold higher than those in uninfected controls,
      and concurrently, IL-10 levels rose markedly with reduction of circulating IL-1
      and IFN-gamma. Treatment with neutralizing anti-IL-10 mAb before D-Gal/SEA
      challenge led to increased IFN-gamma levels in mice with MAIDS, and resulted in a
      dose-dependent mortality. In contrast, mice with MAIDS were more susceptible to
      the toxicity of bacterial endotoxin LPS than were uninfected controls.
      Administration of 100 micrograms LPS alone induced 50% lethality in mice infected
      with MAIDS virus 8 wk previously but not in uninfected controls. Administration
      of 10 micrograms LPS caused acute shock in D-Gal-sensitized mice with MAIDS. Peak
      TNF-alpha levels in these mice after LPS challenge were increased more than 10
      fold, whereas IL-10 levels were one-third of those after SEA challenge. Moreover,
      serum IFN-gamma was undetectable in uninfected controls and rose to 1063 +/- 483
      pg/ml in mice with MAIDS 4 h after LPS challenge. These results suggest that
      aberrant profiles of cytokine production are crucial in determining fatal outcome
      in these two types of septic shock in MAIDS.

PMID- 7561045
TI  - Sand fly vector saliva selectively modulates macrophage functions that inhibit
      killing of Leishmania major and nitric oxide production.
AB  - The saliva of Phlebotomus papatasi, a sand fly vector for Leishmania major,
      contains a factor that exacerbates leishmaniasis and may be required for the
      establishment of infection with Leishmania in nature. We have examined the effect
      of sand fly saliva on various macrophage functions in vitro. Our data demonstrate
      that although saliva does not alter uptake of L. major by macrophages, it
      inhibits the ability of IFN-gamma to activate macrophages to kill the
      intracellular parasite. This inhibition of parasite killing is observed when both
      the promastigote and amastigote forms of the parasite are used for infection.
      Furthermore, this inhibition of parasite destruction correlates with reduction of
      nitric oxide (NO) production, suggesting that the ability of sand fly saliva to
      reduce nitrogen oxidation in response to IFN-gamma may be responsible for the
      inhibitory effect of saliva on intracellular killing of L. major. Finally,
      despite the fact that saliva inhibits NO production in IFN-gamma-activated
      macrophages, it does not prevent IFN-gamma from up-regulating class II MHC
      expression on macrophages. This suggests that the immunosuppressive effect of
      sand fly saliva on the macrophage is targeted to certain critical, but not all,
      functions of the cell.

PMID- 7561046
TI  - Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation
      and immunity by a high melanin-producing strain of Cryptococcus neoformans.
AB  - The interaction(s) between cryptococcal virulence factors and leukocytes involved
      in generating protective cell-mediated immunity is not well defined.
      Intratracheal inoculation of Cryptococcus neoformans strain 52 induced a vigorous
      T cell-mediated pulmonary inflammatory response that controlled the growth of the
      organism. In contrast, strain 145 induced a pulmonary inflammatory response that
      was delayed in onset, slower to develop, and ineffective in controlling the
      infection. In addition, the expansion of cryptococcus-specific lymphocytes in the
      pulmonary lymph nodes and titer of specific Abs in the serum of strain 145
      infected mice were both diminished markedly. Of the known cryptococcal virulence
      factors, these two strains differed only in melanin production (52-low and 145
      high). Heat-killed strain 145 cryptococci (HKC-145) that had been rendered
      melanin-negative induced TNF-alpha production by alveolar macrophages in vitro
      and stimulated vigorous cryptococcus-specific lymphoproliferation. In contrast,
      high melanin-containing HKC-145 inhibited TNF-alpha production and
      lymphoproliferation. In vivo, mice infected with melanin low strain 52, but not
      melanin high strain 145, had elevated levels of TNF-alpha in the bronchoalveolar
      lavage fluid. Mice co-infected with strains 145 and 52 generated a pulmonary
      inflammatory response resulting in increased long-term survival. Taken together,
      these studies demonstrate that melanin does not protect cryptococci from being
      eliminated in vivo by recruited, activated effector cells; but melanin can
      inhibit the recognition of the organism by host defenses, thereby down-regulating
      the afferent phase of T cell-mediated immunity, e.g., TNF-alpha production and
      lymphoproliferation.

PMID- 7561047
TI  - Defective regional immunity in the respiratory tract of neonates is attributable
      to hyporesponsiveness of local dendritic cells to activation signals.
AB  - A variety of studies suggest that the increased susceptibility of neonates to
      allergic and infectious respiratory diseases is due to delayed postnatal
      maturation of local mucosal immune function. We have recently demonstrated that
      the postnatal development of the major resident APC population in the respiratory
      tract (RT), class II MHC (Ia)-bearing dendritic cells (DC), is delayed relative
      to that in other tissues, and that both the intensity of Ia expression on these
      RTDC and their density within respiratory epithelia remain low until after
      weaning. The present study focuses on the functional capacity of neonatal RTDC
      and their responses to exogenous stimuli, and demonstrates that 1) infant Ia+
      RTDC respond poorly to GM-CSF, under conditions that stimulate high levels of Ia
      expression and concomitant APC activity in adult cells; 2) both infant and adult
      RTDC contain a subpopulation of Ia- cells recognized by mAb OX62 that also
      respond poorly to GM-CSF; 3) inhalation of microbial stimuli or parenteral
      administration of IFN-gamma triggers rapid recruitment of DC into the airway
      epithelium and lung parenchyma of adults; this response is markedly attenuated in
      newborns and does not attain levels of competence until after weaning; and 4)
      endogenous macrophage-mediated suppression of the RTDC response to GM-CSF, the
      principal mechanism limiting in situ DC functional maturation in the adult lung,
      is highly active in the neonates. Taken together with earlier evidence of the
      relatively rapid postnatal development of T and B cell function in these animals,
      the present findings suggest that the sluggish performance of respiratory mucosal
      immune function(s) during infancy is attributable primarily to delayed maturation
      of local DC populations.

PMID- 7561048
TI  - CD40 ligand is required for resolution of Pneumocystis carinii pneumonia in mice.
AB  - The role of the CD40-CD40 ligand (CD40L) interaction in resolution of
      Pneumocystis carinii (PC) pneumonia (PCP) was assessed in a PC-infected severe
      combined immunodeficiency (SCID) mouse reconstitution model using an anti-CD40L
      mAb to block CD40L. SCID mice infected with PC were reconstituted with
      unfractionated spleen cells from immunocompetent donors and given either anti
      CD40L mAb or an irrelevant control mAb. Mice given the control mAb resolved the
      PC infection, whereas those given the anti-CD40L mAb did not. That anti-CD40L mAb
      also inhibited PC-specific IgG production is consistent with the possibility that
      cognate CD4+ T cell-B cell interactions are important in PCP resolution. The
      experiment was then repeated, except that the PC-infected SCID mice were
      reconstituted with purified CD4+ T cells only. Again, the control mAb-treated
      group resolved the PCP, whereas mice treated with anti-CD40L mAb did not. In the
      second experiment, inhibition of resolution of PCP in the anti-CD40L mAb group
      was not the result of blocking CD4+ T cell-dependent activation of PC-specific B
      cells. The results are consistent with the possibility that resistance to PCP may
      involve interaction between B cells and CD4+ T cells via the CD40-CD40L pathway.
      However, results additionally indicate that inhibition of CD40-CD40L interaction
      ablates resistance to PCP by inhibiting the interaction of T cells with some cell
      other than B cells.

PMID- 7561049
TI  - Metabolic requirements for induction of contact hypersensitivity to immunotoxic
      polyaromatic hydrocarbons.
AB  - Experiments were performed to define the metabolic requirements for induction of
      contact hypersensitivity to polyaromatic hydrocarbons (PAHs), environmental
      xenobiotics that are both immunotoxic and carcinogenic. Evidence that conversion
      of the parent compound to a reactive metabolite was necessary for the development
      of contact hypersensitivity included the fact 1) that contact hypersensitivity to
      the polyaromatic hydrocarbon dimethylbenz(a)anthracene (DMBA) only occurred in
      strains of mice that could metabolize the compound, 2) that among the PAHs, only
      those that could induce aryl hydrocarbon hydroxylase, the rate-limiting enzyme in
      the PAH metabolic pathway, were immunogenic, and 3) that inhibitors of PAH
      metabolism reduced DMBA contact hypersensitivity. Cells from the XS52 Langerhans
      cell-like dendritic cell line were able to metabolize the PAH benzo(a)pyrene to
      its diol, quinone, and phenol metabolites. GM-CSF augmented benzo(a)pyrene
      metabolism in XS52 cells. Finally, in vivo depletion of CD8+, but not CD4+, T
      cell populations inhibited contact hypersensitivity to DMBA. The implications of
      these experiments are that at least for some contact allergens, the metabolic
      status of the host is a key determinant of individual susceptibility to the
      development of allergic contact dermatitis, and the metabolic pathway of an
      individual hapten may have ramifications for the T cell subpopulation-CD4 or CD8
      that is activated.

PMID- 7561050
TI  - Selective inhibition of E-selectin, vascular cell adhesion molecule-1, and
      intercellular adhesion molecule-1 expression by inhibitors of I kappa B-alpha
      phosphorylation.
AB  - The promoters of the E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and
      intercellular adhesion molecule-1 (ICAM-1) genes contain recognition sequences
      for the inducible nuclear transcription factor kappa B (NF-kappa B). We
      demonstrate that the appearance of NF-kappa B DNA-binding activity in the nucleus
      of TNF-alpha-stimulated HUVEC is associated with the rapid phosphorylation and
      subsequent degradation of I kappa B-alpha, the cytoplasmic inhibitor of NF-kappa
      B. Serine protease inhibitors prevented the TNF-alpha-induced accumulation of
      phosphorylated I kappa B-alpha, and prevented I kappa B-alpha degradation and the
      appearance of NF-kappa B DNA-binding activity. These inhibitors had no direct
      effect upon the ability of NF-kappa B to bind its cognate recognition sequences,
      nor upon the DNA-binding activities of other transcription factors. Inhibition of
      I kappa B-alpha proteolysis resulted in the inhibition of the cytokine- and LPS
      induced transcriptional up-regulation and cell-surface expression of E-selectin,
      VCAM-1, and ICAM-1. In contrast, the TNF-alpha-induced expression of plasminogen
      activator inhibitor-1 and the constitutive expression of ICAM-2 were unaffected.
      These inhibitors also had no effect on cellular viability or rates of RNA or
      protein synthesis. Inhibitors of other proteases and various protein kinases had
      no effect on the cytokine-induced expression of these endothelial adhesion
      molecules. These findings indicate that it is possible, using a single
      pharmacologic agent, to selectively inhibit the expression of the E-selectin,
      VCAM-1, and ICAM-1 genes without affecting the constitutive or inducible
      expression of other genes. Pharmacologic inhibition of I kappa B-alpha
      proteolysis represents a novel approach to the development of anti-inflammatory
      therapeutics.

PMID- 7561051
TI  - In vivo regulation of macrophage IL-12 production during type 1 and type 2
      cytokine-mediated granuloma formation.
AB  - IL-12 is a pivitol cytokine that promotes NK cell activity and Th1 (type 1)
      mediated immune responses. This study analyzed the cytokines that regulate
      macrophage (M phi) IL-12 production in vitro and in vivo. IL-12 was produced by
      elicited but not resident peritoneal M phi stimulated with endotoxin. Addition of
      graded doses of cytokines (0.1 to 10 ng/ml) indicated that the Th1-related (type
      1) cytokine, IFN-gamma, augmented endotoxin-stimulated IL-12 production by nearly
      sixfold in oil-elicited M phi. TNF-alpha also increased production but only at
      the 10 ng/ml concentration. In contrast, the Th2-related (type 2) cytokines, IL-4
      and especially IL-10, were profoundly inhibitory. IL-1 beta and IL-2 had no
      effect. For in vivo analysis, type 1 and type 2 cytokine-mediated lung granulomas
      (GR) were induced in presensitized mice by embolization of beads coupled to
      purified protein derivative of Mycobacteria tuberculosis or soluble Ags derived
      from Schistosoma mansoni eggs. Analysis of M phi isolated from type 1, type 2, or
      control pulmonary GR revealed that M phi of type 2 GR develop impaired IL-12
      producing capacity. Depletion studies using anti-IFN, anti-IL-12, anti-IL-10, and
      anti-IL-4 neutralizing polyclonal Abs corroborated the in vitro studies. Anti-IFN
      or anti-IL-12 reduced IL-12 production by M phi from type 1 GR (70 to 80%) as
      well as IFN and IL-12 production by draining lymph nodes (75 to 90%). Conversely,
      anti-IL-10 and anti-IL-4 reversed the impaired IL-12 production observed in type
      2 GR M phi. These data indicate a positive feedback stimulation of IL-12
      production by IFN that is regulated by IL-10 and IL-4 in vivo.

PMID- 7561052
TI  - Role of the hypothalamus-pituitary-adrenal axis in the regulation of TNF
      production in mice. Effect of stress and inhibition of endogenous
      glucocorticoids.
AB  - Glucocorticoids (GC) are known inhibitors of TNF production and are increased by
      endotoxin (LPS) through a stimulation of the hypothalamus-pituitary-adrenal axis
      (HPAA), suggesting a feedback mechanism. We tried different approaches to study
      the role of the HPAA and endogenous GC in the regulation of TNF production.
      Cyanoketone, a GC synthesis inhibitor, inhibited corticosterone (CS) induction by
      LPS and increased LPS-induced serum TNF levels. Similar results were obtained by
      pretreating mice with anticorticotropin-releasing hormone Abs. Administration of
      adrenocorticotropic hormone increased blood CS and inhibited LPS-induced serum
      TNF. TNF production by mouse blood stimulated in vitro with LPS was inhibited by
      addition of CS. Blood from stressed or adrenocorticotropic-releasing hormone
      treated mice (in which CS levels are elevated) stimulated ex vivo with LPS
      produced significantly less TNF than blood from control mice. Normal TNF
      production was restored by the addition of the GC receptor antagonist RU 38486,
      indicating a role for the elevated endogenous CS levels in the inhibition of TNF
      production. These data indicate that the HPAA is a major regulator of TNF
      production.

PMID- 7561053
TI  - Activation and interaction with protein kinase C of a cytoplasmic tyrosine
      kinase, Itk/Tsk/Emt, on Fc epsilon RI cross-linking on mast cells.
AB  - Cross-linking of the high-affinity IgE receptor (Fc epsilon RI) on mast cells
      induces rapid phosphorylation on serine, threonine, and tyrosine residues and
      increases the enzymatic activity, of a Tec subfamily tyrosine kinase, Itk/Tsk/Emt
      (Emt). The pleckstrin homology domain of Emt at its amino-terminal interacts
      directly with multiple isoforms of protein kinase C (PKC) in vitro. In addition,
      a portion of Emt is physically associated with multiple isoforms of PKC in intact
      mast cells. PKC phosphorylates a bacterial fusion protein containing the
      pleckstrin homology domain of Emt in vitro. Coexpression of Emt in COS-7 cells
      with Ca(2+)-dependent PKC isoforms (alpha, beta I, or beta II) induces an
      enhancement in tyrosine phosphorylation of Emt. In vivo inhibition of PKC
      expression or activity attenuates tyrosine phosphorylation and enzymatic activity
      of Emt induced upon Fc epsilon RI cross-linking. These data collectively suggest
      that PKC phosphorylates Emt and activates its autophosphorylating activity.
      Alternatively, PKC could activate another tyrosine kinase that phosphorylates
      Emt, or PKC-mediated phosphorylation of Emt may render it a target for another
      tyrosine kinase. In any case, PKC appears to play a major role in the activation
      of Emt induced upon Fc epsilon RI cross-linking.

PMID- 7561054
TI  - The actin-binding protein, lymphocyte-specific protein 1, is expressed in human
      leukocytes and human myeloid and lymphoid cell lines.
AB  - Lymphocyte-specific protein 1 (LSP1) was originally reported as a lymphocyte
      specific actin-binding protein using murine LSP1 probes. Subsequently, we
      identified LSP1 in polymorphonuclear neutrophils (PMN) and showed that it is the
      overexpressed 47-kDa protein in neutrophil actin dysfunction with 47- and 89-kDa
      abnormalities. This suggests that regulation of LSP1 expression in myeloid cells
      may be a functionally important event. LSP1 expression in human leukocytes,
      lymphoid cell lines, and myeloid cell lines (PLB985, HL60, and U937), uninduced
      (U) or induced to granulocytic (GI) or monocytic (MI) differentiation, was
      analyzed by Northern blot and immunoblot. By immunoblot, LSP1 is strongly
      expressed in PMN, less expressed in lymphocytes and monocytes (30-40% and 55-65%
      of the PMN level, respectively). By immunoblot and Northern blot, LSP1 is
      minimally expressed in U-PLB985 and U-HL60 (< 10% of the PMN level) and is weakly
      expressed in the B lymphoid cell line Daudi, but is not expressed in the pro-B,
      pre-B, T lymphoid cell lines tested, U-U937 or MI-U937. LSP1 mRNA and protein are
      up-regulated in GI-PLB985, GI-HL60, and MI-HL60. In HL60, LSP1 mRNA and protein
      increase in parallel to a maximum of eightfold the basal level on days 5 to 6 of
      granulocytic differentiation and four- to fivefold the basal level on day 3 of
      monocytic differentiation. The results show that LSP1 is expressed in all human
      leukocytes, and its expression is up-regulated during granulocytic and monocytic
      differentiation of myeloid cells in vitro. Since its overexpression is implicated
      in the functional pathogenesis of a novel human neutrophil motile dysfunction and
      microfilamentous cytoskeletal abnormality (NAD 47/89), finding LSP1 in all human
      leukocytes suggests that it plays a role in regulating microfilamentous
      cytoskeleton structure and motile function in all leukocytes. Since the protein
      is not lymphocyte specific and is an F-actin binding protein, and its isoforms
      are expressed in stromal and embryonic mesenchymal cells, we propose that the
      protein's name be changed to leufactin, as an abbreviated form of leukocyte F
      actin binding protein.

PMID- 7561055
TI  - Superantigen-induced collagenase gene expression in human IFN-gamma-treated
      fibroblast-like synoviocytes involves prostaglandin E2. Evidence for a role of
      cyclooxygenase-2 and cytosolic phospholipase A2.
AB  - MHC class II molecules expressed in lymphoid and nonlymphoid cells act as signal
      transducer molecules. We demonstrate that engagement of MHC class II molecules on
      human IFN-gamma-treated fibroblast-like synoviocytes by their natural ligand, the
      staphylococcal enterotoxin A (SEA), selectively induces the production of
      interstitial collagenase over the expression of the tissue inhibitor of
      metalloproteinase (TIMP). Collagenase gene expression required de novo protein
      synthesis and was accompanied by high levels of PGE2 production, suggesting its
      implication in this response. Two inhibitors that affect prostaglandin
      biosynthesis, indomethacin and arachidonyl-trifluoromethyl-ketone, inhibited both
      PGE2 production and collagenase gene expression. The addition of exogenous PGE2
      to inhibitor-treated cells partially restored the SEA-induced collagenase,
      indicating a role for PGE2 in this response. As cyclooxygenases (COX-1 and -2),
      cytosolic phospholipase A2 (cPLA2), and secreted PLA2 (sPLA2) are the enzymes
      potentially implicated in prostaglandin synthesis, their involvement in SEA
      induced collagenase was investigated. The mRNA levels of COX-2 and cPLA2 rapidly
      increased following ligation of MHC class II molecules, while COX-1 and sPLA2
      mRNA levels were unchanged and transiently depressed, respectively. SEA-induced
      COX-2 mRNA was translated adequately to protein, whereas cPLA2 protein level was
      not enhanced, but rapidly phosphorylated, a process previously linked to the
      enzyme activation. In conclusion, this work demonstrates a selective induction of
      collagenase gene expression over its natural inhibitor TIMP in human IFN-gamma
      treated fibroblast-like synoviocytes mediated, at least in part, by PGE2, and
      provides evidence that signaling via MHC class II molecules induces the
      production of PGE2 through enhanced production of COX-2 and possibly activation
      of the cPLA2.

PMID- 7561056
TI  - Characterization of intercellular adhesion molecule-1 ectodomain (sICAM-1) as an
      inhibitor of lymphocyte function-associated molecule-1 interaction with ICAM-1.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig superfamily,
      contains five Ig-like domains comprising the extracellular portion of the
      molecule, and interacts with lymphocyte function-associated molecule-1 (LFA-1), a
      member of the beta 2-integrin family. LFA-1/ICAM-1 interaction is important in a
      variety of cellular events including Ag-specific T cell activation and leukocyte
      transendothelial migration. Recently, a soluble circulating form of ICAM-1 has
      been detected in human serum that appears to result from the proteolytic cleavage
      of membrane ICAM-1. Native and recombinant soluble forms of ICAM-1 have been
      reported to inhibit LFA-1/ICAM-mediated adhesion in vitro, and it is conceivable
      that circulating forms of soluble ICAM-1 are regulators of LFA-1/ICAM-1-mediated
      cell-cell interaction in vivo. We have investigated the properties of the ICAM-1
      ectodomain (sICAM453) as an inhibitor of LFA-1 interaction with ICAM-1 in cell-
      and molecule-based systems. The results show clearly that recombinant sICAM453
      can inhibit LFA-1/ICAM-1 interaction. Soluble ICAM-1 inhibited LFA-1-mediated
      cell adhesion to immobilized sICAM453 and homotypic T-cell aggregation with IC50
      in the 20 to 40 microM range. Definitive evidence that sICAM-1 can inhibit LFA-1
      interaction with ICAM-1 was obtained by showing that the sICAM-1 inhibited the
      interaction between LFA-1 protein micelles and ICAM-1 immobilized on plastic.
      These results clearly show that sICAM453 can bind to LFA-1 and competitively
      inhibit ICAM-1/LFA-1-mediated cell-cell interaction, albeit at concentrations
      much greater than found in plasma. As a consequence, it is unlikely that sICAM-1
      would antagonize ICAM-1/LFA-1-mediated cellular events in vivo.

PMID- 7561057
TI  - Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces
      multinucleated giant cell formation of monocytes and HIV gp160-mediated cell
      fusion. FRP-1 and 4F2/CD98 are identical molecules.
AB  - Fusion regulatory protein (FRP)-1 regulates virus-mediated cell fusion and fusion
      of monocytes. Eleven of fifteen N-terminal amino acids of FRP-1 were the same as
      the amino acid sequence of 4F2/CD98 heavy chain. FRP-1 molecules were detected in
      Con A- or IL-2-stimulated lymphocytes, while FRP-1 was rare on resting
      lymphocytes. These properties of FRP-1 are similar to those of 4F2/CD98.
      Treatment of monocytes with anti-4F2/CD98 mAbs resulted in cell fusion, and other
      mAbs directed against 4F2/CD98 induced formation of multinucleated giant cells of
      Cd+U2ME-7 cells, a CD4+U937 cell line transfected with the HIV gp160 gene. Both
      anti-4F2/CD98 and anti-FRP-1 mAbs reacted with murine L929 cells expressing human
      4F2/CD98 transiently or constitutively. When Newcastle disease virus (NDV)
      infected L929 cells expressing human FRP-1/CD98 were incubated with mAb 4-5-1, an
      anti-FRP-1 mAb, multinucleated giant cells were induced; thus, FRP-1/CD98
      molecules expressed in L929 cells are functional for fusion regulatory activity.

PMID- 7561058
TI  - Two structurally distinct kappa B sequence motifs cooperatively control LPS
      induced KC gene transcription in mouse macrophages.
AB  - The mouse KC gene is an alpha-chemokine gene whose transcription is induced in
      mononuclear phagocytes by LPS. DNA sequences necessary for transcriptional
      control of KC by LPS were identified in the region flanking the transcription
      start site. Transient transfection analysis in macrophages using deletion mutants
      of a 1.5-kb sequence placed in front of the chloramphenicol acetyl transferase
      (CAT) gene identified an LPS-responsive region between residues -104 and +30.
      This region contained two kappa B sequence motifs. The first motif (position -70
      to -59, kappa beta 1) is highly conserved in all three human GRO genes and in the
      mouse macrophage inflammatory protein-2 (MIP-2) gene. The second kappa B motif
      (position -89 to -78, kappa B2) was conserved only between the mouse and the rat
      KC genes. Consistent with previous reports, the highly conserved kappa B site
      (kappa B1) was essential for LPS inducibility. Surprisingly, the distal kappa B
      site (kappa B2) was also necessary for optimal response; mutation of either kappa
      B site markedly reduced sensitivity to LPS in RAW264.7 cells and to TNF-alpha in
      NIH 3T3 fibroblasts. Although both kappa B1 and kappa B2 sequences were able to
      bind members of the Rel homology family, including NF kappa B1 (P50), RelA (65),
      and c-Rel, the kappa B1 site bound these factors with higher affinity and
      functioned more effectively than the kappa B2 site in a heterologous promoter.
      These findings demonstrate that transcriptional control of the KC gene requires
      cooperation between two kappa B sites and is thus distinct from that of the three
      human GRO genes and the mouse MIP-2 gene.

PMID- 7561059
TI  - Simultaneous cross-linking by two nontriggering bivalent ligands causes
      synergistic signaling of IgE Fc epsilon RI complexes.
AB  - We have used two bivalent ligands that bind IgE to study the relationship between
      the aggregation of receptors with high affinity for IgE (Fc epsilon RI) and the
      responses (receptor immobilization, Ca2+ influx, and degranulation) of rat
      basophilic leukemia (RBL-2H3) cells. One of these is a symmetric bivalent ligand,
      N,N'-bis[[epsilon-[(2,4-dinitrophenyl)amino]caproyl]-L-tyrosyl]-L- cystine
      ((DCT)2-cys), which binds specifically to the combining sites of a mAb anti-DNP
      IgE and efficiently cross-links cell surface IgE, but does not trigger
      significant degranulation or increases in intracellular Ca2+. Several lines of
      evidence, including lateral mobility measurements, indicate that this ligand
      preferentially forms stable cyclic complexes containing two (DCT)2-cys and two
      IgE. The second ligand is a mAb anti-IgE, B1E3, which causes lateral mobility
      changes consistent with dimerized IgE-Fc epsilon RI and also does not trigger
      increases in intracellular Ca2+ or degranulation. The two ligands together
      trigger robust responses. In the presence of B1E3, (DCT)2-cys causes
      immobilization of IgE-Fc epsilon RI in a broad concentration range; in a more
      narrow concentration range, it is a potent stimulant of changes in both
      degranulation and Ca2+. We have compared the dose-response curves for cellular
      activation to simulated IgE aggregation curves, i.e., curves that predict the
      equilibrium IgE aggregate size distribution as a function of the (DCT)2-cys
      concentration. Our results indicate that maximal cellular activation occurs at a
      much higher (DCT)2-cys concentration than maximal IgE aggregation. When IgE
      aggregation is maximal, almost all aggregated IgE is in cyclic dimers. Thus,
      cyclic dimers appear to be functionally ineffective, even after they have been
      cross-linked by B1E3. Aggregated IgE-Fc epsilon RI that is effective in
      stimulating a cellular response may have particular structural or dynamic
      properties that allow critical interactions for initiating the signaling cascade.

PMID- 7561060
TI  - A soluble gradient of endogenous monocyte chemoattractant protein-1 promotes the
      transendothelial migration of monocytes in vitro.
AB  - Chemokines secreted by endothelium may promote diapedesis of leukocytes by a
      gradient-dependent chemotactic mechanism or by stimulating random motility so
      that leukocytes transmigrate in a gradient-independent manner. Alternatively,
      chemokines may bind to endothelium and extracellular matrix to stimulate
      haptotactic migration. We first analyzed the role of the chemokine monocyte
      chemoattractant protein-1 (MCP-1) in the migration of human monocytes across
      untreated or IL-1-stimulated HUVEC monolayers cultured on human amnion. Then we
      further examined whether MCP-1-dependent transmigration occurred through a
      chemokinetic, chemotactic, or haptotactic mechanism. A neutralizing mAb against
      MCP-1 inhibited passage of monocytes across untreated or IL-1-stimulated HUVEC by
      74 +/- 3% and 45 +/- 4%, respectively. Addition of MCP-1 itself to the apical
      compartment of unstimulated HUVEC/amnion cultures also reduced the transmigration
      of monocytes, in this instance by 73 +/- 9%. MCP-1 suppressed diapedesis only
      when present above the endothelium at a concentration equal to or greater than
      that endogenously deposited beneath the endothelium, and its inhibitory action
      could be overcome by addition of more concentrated MCP-1 below the HUVEC
      cultures. As much as 90% of the MCP-1 secreted into the underlying basement
      membrane and connective tissue could be washed out of HUVEC/amnion cultures; this
      procedure decreased transmigration by 69 +/- 4%. These data indicate that MCP-1
      promotes transmigration of monocytes, but only when present in a gradient across
      endothelial monolayers. They further suggest that this gradient is predominantly
      soluble, rather than haptotactic.

PMID- 7561061
TI  - Intercellular adhesion molecule-2 (CD102) binds to the leukocyte integrin
      CD11b/CD18 through the A domain.
AB  - The interactions between the leukocyte-specific beta 2-integrins cluster of
      differentiation (CD) Ag CD11/CD18 and their ligands, the intercellular adhesion
      molecules (ICAMs), play important roles in many adhesion-dependent leukocyte
      functions. ICAM-1 is known to be a ligand for both CD11a/CD18 and CD11b/CD18.
      ICAM-2, whose two extracellular Ig domains show the highest homology to the two
      NH2-terminal domains of ICAM-1, has been previously shown to be a ligand for
      CD11a/CD18. We recently found that a 22-amino acid CD11a/CD18-binding peptide,
      P1, derived from the first domain of ICAM-2, also binds to purified CD11b/CD18.
      In the present study, we demonstrate that the ICAM-2 protein interacts with
      CD11b/CD18, and the binding is through the CD11b A domain.

PMID- 7561062
TI  - Structural restriction in the heavy chain CDR3 of human rheumatoid factors.
AB  - We have compared the variable regions of 14 new IgM rheumatoid factors (RFs),
      produced in healthy human immunized donors (HIDs) with RFs originating from
      patients with rheumatoid arthritis (RA) and monoclonal Ig RFs (paraproteins or M
      components, MC). Two groups with very restricted variable region structures were
      found. Twelve RFs (3 HID, 3 MC, and 6 RA) encoded by variable heavy (VH) chain
      germ-line genes with closest homology to DP-10 co-express the Kv325 variable
      light (VL) chain germ-line gene. These RFs have a remarkable restriction in the
      length (12-14 amino acids) and structure of the CDRH3. One HID RF has a CDRH3
      only two amino acids different from the CDRH3 of a MC RF. Two sets of clonally
      related RFs, one from an RA patient and one from an HID, have CDRH3s that differ
      by only three amino acids. Five RFs (3 HID, 1 MC, and 1 RA) encoded by VH germ
      line gene segments with closest homology to DP-54 all use the Kv328 VL germ-line
      gene combined to J kappa 1. Four are rearranged to the D21/9 D segment in the
      same reading frame, with CDRH3s of 16 to 17 amino acids. Three RFs (1 HID, 1 RA,
      and 1 MC) have CDRH3s differing by only three amino acids. The highly homologous
      V-regions in RFs from these two groups imply an initial selection to very
      similar, if not identical, epitopes. However, it remains to be seen whether
      somatic hypermutation alters the fine specificity of these autoantibodies.

PMID- 7561064
TI  - Contribution of IL-1, CD14, and CD13 in the increased IL-6 production induced by
      in vitro monocyte-synoviocyte interactions.
AB  - Rheumatoid synovitis is characterized by an infiltration of mononuclear cells and
      by the proliferation of synoviocytes. Monocytes and synoviocytes are major
      producers of cytokines, growth factors, and enzymes that contribute to the
      rheumatoid arthritis (RA) process. Since they are in close contact in vivo, we
      engaged in an in vitro study of the functional consequences of their
      interactions. Coculture of unstimulated elutriated normal blood monocytes over RA
      synoviocytes resulted in a synergistic increase of the production of IL-6,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory
      factor (LIF), and IL-8, when compared with their respective production in culture
      alone. In contrast, cytokines such as IL-10, IL-1 beta, IL-1 alpha, and TNF-alpha
      could not be detected. The IL-6 production in coculture was further increased by
      the addition of IL-1 beta, GM-CSF, IFN-gamma, or TNF-alpha, but was inhibited by
      the addition of IL-10, IL-4, IL-13, or IL-1Ra, an effect reverted by the addition
      of IL-1 beta. Moreover, an inhibition was also observed with anti-CD14 mAb and
      newly raised mAbs directed against RA synoviocytes. Under reducing conditions,
      the mAb SY12 precipitated a 150-kDa surface membrane protein, identified as amino
      peptidase N (CD13/AP-N). Collectively, these results indicate that 1) monocytes
      and synoviocytes interact with each other to produce proinflammatory cytokines,
      2) pro- and antiinflammatory cytokines have opposite effects on IL-6 production,
      and 3) molecules such as IL-1, CD14, and CD13 are involved.

PMID- 7561063
TI  - Influence of heavy chain constant regions on antigen binding and HIV-1
      neutralization by a human monoclonal antibody.
AB  - F105, a neutralizing IgG1 kappa human mAb, is reactive with a discontinuous
      epitope within the gp120 CD4 binding site. Because isotype usage may affect Ab
      function, we examined the effect of isotype on Ag/Ab interactions and HIV-1
      neutralization. An IgG3 kappa Ab was prepared by linking the variable regions of
      F105 to cloned human kappa and gamma 3 constant regions. Immunoreactivity of F105
      IgG1 and IgG3 with IIIB-, MN-, and RF-infected cells was equivalent. Inhibition
      of binding and fusion of IIIB to uninfected cells and neutralization of IIIB
      virus was comparable for F105 IgG1 and IgG3, with 14 to 23 micrograms/ml required
      for 90% neutralization. In contrast, F105 IgG3 was marginally more effective at
      inhibition of MN binding/fusion and significantly more effective at
      neutralization of MN virus (62 micrograms/ml for IgG3 and > 100 micrograms/ml for
      IgG1 to achieve 90% neutralization). Despite high affinity binding to RF-infected
      cells, F105 IgG1 minimally neutralizes free RF virus. F105 IgG3 is dramatically
      more effective against the RF isolate, with 2 to 20 micrograms/ml of Ab required
      for 50% neutralization. Both isotypes were relatively ineffective at inhibition
      of RF binding/fusion. Thus, whereas affinity with native Ags on the surface of
      HIV-1-infected cells was unaffected by heavy chain constant regions, Ab isotype
      can strongly influence virion neutralization. Structural changes in gp120, as a
      result of increased flexibility conferred by the elongated IgG3 hinge region, are
      suggested as a possible mechanism to increase neutralization of selected HIV-1
      isolates. These results may have significant implications in the design of
      immunotherapeutic and vaccine agents.

PMID- 7561065
TI  - Oral administration of an immunodominant human collagen peptide modulates
      collagen-induced arthritis.
AB  - Human type II collagen (HuCII) may be one of the autoantigens involved in human
      rheumatoid arthritis (RA). By using over-lapping peptides, we have previously
      described an immunodominant region (HuCII.250-270) on HuCII. In the present
      study, this 21-mer HuCII.250-270 peptide was used as tolerogen, and its effect on
      both early and effector phase of collagen-induced arthritis (CIA) was examined.
      Upon immunization with HuCII-derived peptide 250-270, HuCII.250-270-tolerized
      mice showed diminished T cell proliferation that was mediated by Th1 cytokine, IL
      2. More interestingly, oral tolerance with HuCII.250-270 peptide diminishes
      primarily a Th1 type of immune response. Arthritis severity was reduced markedly
      in mice orally tolerized with HuCII.250-270 peptide both at early and effector
      phases. Suppression of CIA at the effector phase by oral administration of HuCII
      peptide suggests a potential immunotherapeutic use of collagen II peptide in the
      treatment of human RA.

PMID- 7561067
TI  - Altered target organ. A mechanism of postrecovery resistance to murine autoimmune
      oophoritis.
AB  - Experimental murine autoimmune oophoritis, a model of human premature ovarian
      failure, is induced by immunization with a peptide of the ZP3 glycoprotein from
      mouse zona pellucida (ZP3(330-340)) in CFA. The ovarian pathology is mediated by
      ZP3-specific, CD4+ T cells, and not by Abs. We now show that mice recovered from
      autoimmune oophoritis in 4 mo, as characterized by regression of ovarian
      inflammation. Recovery was associated with disease resistance upon rechallenge
      with ZP3(330-340) in CFA. Oophoritis resistance was not explicable by
      immunosuppressive effect of CFA priming, nor by suppression of pathogenic T
      cells. ZP3-specific, proliferative T cell response could be detected, and a ZP3
      specific, IFN-gamma-producing pathogenic T cell line was derived readily from the
      recovered mice by in vitro stimulation with the ZP3(330-340) peptide. Moreover,
      recovered mice, when challenged with ZP3(330-340) in CFA, produced Abs of IgG
      class to the ZP3(330-340) peptide. Suppressor T cells are not readily
      demonstrable. Most importantly, oophoritis occurred in normal ovaries implanted
      under the renal capsule of the recovered mice. That oophoritis developed in the
      implanted ovaries, but spared the endogenous ovaries, further indicates that the
      latter is refractory to oophoritis. Disease resistance of the ovaries is not
      explicable by limitation of accessible target Ags. When mated, recovered mice
      were fertile and produced normal litters; and, as recipients of a ZP3-specific T
      cell line, their ovaries developed oophoritis. We conclude that altered local
      environment of the target organ following autoimmune disease recovery can
      contribute to the complex disease-resistant state.

PMID- 7561068
TI  - Anti-CD3:anti-IL-2 receptor-bispecific mAb-mediated immunomodulation. Low
      systemic toxicity, differential effect on lymphoid tissue, and inhibition of cell
      mediated hypersensitivity.
AB  - An anti-CD3:anti-CD25 (CD3,25) bispecific mAb was developed with the objective of
      combining the advantages of the parent anti-CD3 and anti-CD25 mAbs. The in vivo
      effects of the CD3,25 were examined in comparison to the parent Abs. The CD3,25
      was well tolerated in vivo, in contrast to the parent anti-CD3 mAb, which induced
      systemic toxicity in recipient animals. Anti-CD3 mAb induced cell death,
      lymphoblast formation, and T cell activation in peripheral lymphoid organs; these
      were observed to a lesser extent in CD3,25-treated animals. In the thymus, anti
      CD3 caused a progressive depletion of the CD4+ CD8+ "double positive" thymocytes,
      which was not seen in CD3,25-treated animals. This finding suggests that
      monovalent CD3 binding is insufficient to induce thymocyte apoptosis. Animals
      treated with a combination of anti-CD3 and anti-CD25 mAbs demonstrated changes in
      the lymphoid organs that were similar to anti-CD3-treated mice. This finding
      demonstrates that the effect of the CD3,25 is different than the sum of the
      parent Abs and suggests that the bispecific nature of the CD3,25 results in a
      reagent with unique immunomodulatory properties. The functional efficacy of the
      CD3,25 was assessed in a murine model of delayed-type hypersensitivity. The
      CD3,25 was as effective as the anti-CD3 mAb in inhibiting the delayed-type
      hypersensitivity reaction and was more effective than the parent anti-CD25 mAb.
      These data demonstrate that appropriately designed bispecific mAbs can be used as
      effective immunosuppressive agents with low systemic toxicity.

PMID- 7561066
TI  - Growth-related gene product alpha. A chemotactic cytokine for neutrophils in
      rheumatoid arthritis.
AB  - Leukocyte recruitment is critical in the inflammation seen in rheumatoid
      arthritis (RA). To determine whether the chemokine growth-related gene product
      alpha (gro alpha) plays a role in this process, we examined synovial tissue (ST),
      synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF
      contained more antigenic gro alpha (mean 5.3 +/- 1.9 ng/ml) than did SFs from
      either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p <
      0.05). RA plasma contained more gro alpha (mean 4.3 +/- 1.8 ng/ml) than normal
      plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10(5)/cells/mI RPMI
      1640/24 h) produced antigenic gro alpha (mean 0.2 +/- 0.1 ng/ml), and this
      production was increased significantly upon incubation with TNF-alpha (mean 1.3
      +/- 0.3 ng/ml) or IL-1 beta (mean 2.3 +/- 0.6 ng/ml) (p < 0.05). Cells from RA SF
      also produced gro alpha: neutrophils (PMNs) (10(7) cells/mI/24 h) produced 3.7 +/
      0.7 ng/ml. RA SF mononuclear cells produced gro alpha, particularly upon
      incubation with LPS or PHA. Immunoreactive ST gro alpha was found in greater
      numbers of RA compared with either OA or normal lining cells, as well as in RA
      compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of
      36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil
      activating peptide-78 accounted for 34%, and gro alpha for 28%, of this activity.
      Combined neutralization of all three chemokines in RA SFs resulted in a mean
      decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These
      results indicate that gro alpha plays an important role in the ingress of PMNs
      into the RA joint.

PMID- 7561069
TI  - Peptide-selected T cell lines from myasthenia gravis patients and controls
      recognize epitopes that are not processed from whole acetylcholine receptor.
AB  - To study pathogenic T helper cells in myasthenia gravis (MG) reacting against the
      acetylcholine receptor (AChR), we have previously selected five CD4+ T cell
      lines/clones from MG patients (or healthy controls) against full-length
      recombinant human AChR alpha subunit (alpha 1-437); these can all recognize AChR
      solubilized from human muscle. Recently, T cells selected with pooled AChR
      subunit synthetic peptides have shown greater heterogeneity than above. Hoping to
      validate that, we have characterized three MG and six control T cell lines
      selected with pooled peptides (averaging 33 residues long) covering the alpha
      subunit sequence; recurring responses to three particular peptides each showed
      preferred HLA class II restrictions--p75-115/DR4, p138-167/DR4, and p309-344/DR3
      (or DR52a). However, none of three lines from MG patients recognized p138-167-
      even one from a previous responder to this epitope in full-length alpha 1-437;
      otherwise they resembled those from controls. Moreover, no peptide-selected line
      responded significantly to whole AChR, alpha 1-437, or even to shorter
      polypeptides sharing one terminus with the peptide, suggesting specificity for
      epitopes not naturally processed by APCs from blood. Of 20 sublines maintained
      with individual peptides, at least 10 responded to independently synthesized
      overlapping sequences, but four others depended on contaminants in the original
      peptides. A single line did recognize one longer polypeptide, but only after
      tryptic digestion; the processing of this cryptic epitope was evidently the
      limiting factor here rather than its concentration or the T cell sensitivity.
      Therefore, while synthetic peptides are essential for mapping epitopes,
      assessment of the pathogenic MG T cell repertoire requires full-length Ag
      processed naturally.

PMID- 7561070
TI  - Pathogenicity of T cells responsive to diverse cryptic epitopes of myelin basic
      protein in the Lewis rat.
AB  - The cellular immunology of experimental autoimmune encephalomyelitis, a model for
      multiple sclerosis, has been studied, for the most part, using T cells directed
      to dominant epitopes of the Ag myelin basic protein (MBP). To characterize T
      cells reactive to cryptic epitopes of MBP, we immunized Lewis rats with each of
      17 overlapping peptides of the 18.5-kDa isoform of rat MBP. We found that, in
      addition to the known 71-90 epitope, six other peptides induced active
      encephalomyelitis in the majority the injected rats. T cell lines raised to six
      different MBP epitopes were encephalitogenic upon adoptive transfer to naive
      rats. In contrast to the T cells specific for the dominant 71-90 peptide, the T
      cell lines reactive to cryptic epitopes were not restricted in their TCR genes to
      V beta 8.2, and some of the lines caused prolonged disease. Thus, T cells of
      different specificities and TCR usage can be pathogenic.

PMID- 7561071
TI  - CD1 and the expanding universe of T cell antigens.

PMID- 7561072
TI  - Activation of telomerase in human lymphocytes and hematopoietic progenitor cells.
AB  - This is the first report describing up-regulation of telomerase activity in human
      normal cells. Telomerase, a ribonucleoprotein enzyme, has been thought to be
      involved in maintaining telomere length stability in germline and most cancer
      cells, but not in normal cells. However, in the present study, we demonstrate
      that telomerase activity is detectable at low levels in normal human T and B
      cells, increases by in vitro mitogenic stimulation, increases in hematopoietic
      progenitor cells upon their proliferation and differentiation, and decreases with
      aging. Understanding the regulation of telomerase activity in normal cells may
      provide important insights not only into the mechanisms of normal cellular
      senescence but also into the mechanisms of telomerase activity deregulation as
      part of cancer development.

PMID- 7561073
TI  - Cytotoxic effect of TNF and lymphotoxin on T lymphoblasts.
AB  - Recombinant TNF and lymphotoxin trigger the apoptotic death of normal mouse and
      human T lymphocyte blasts in vitro. This cytotoxic effect does not involve the
      Fas death pathway and differs from the TNF-triggered death of tumor cells in
      several respects: 1) It is a slower process, requiring 2 to 3 days; 2) it is
      blocked, rather than enhanced, by cycloheximide; and 3) based on the agonistic
      effect of anti-TNF receptor Abs, it involves a synergistic effect of both the 55
      kDa TNFR1 and the 75-kDa TNFR2, as opposed to the dominance of TNFR1 for tumor
      cytotoxicity. The TNF-induced death of blasts is potently inhibited by IL-2, as
      well as by IL-1, IL-4, IFN-gamma, and IL-12. Because activated T cells secrete
      both TNF and LT, these findings reveal a new pathway for Ag-induced down
      modulation of T cell responses.

PMID- 7561074
TI  - Laser light suicide of proliferating virus-specific CD8+ T cells in an in vivo
      response.
AB  - Virus-specific CD8+ CTL precursor (CTLp) frequencies are a function of rates of
      clonal expansion and loss, both of which are difficult to assess in vivo.
      Proliferating T cells incorporate the nucleoside analogue 5-bromo-2'-deoxyuridine
      (BrdU), making them sensitive to light-induced apoptotic cell death (suicide).
      Mice were infected with an influenza A virus, then given 50 mg of BrdU 24 h
      before sampling. Exposure of freshly isolated, CD8-labeled T cells to the laser
      beam of the flow cytometer resulted in the elimination of > 90% of the responding
      CTLp. The effect was obvious for the regional lymph node from day 6 to day 12
      after priming, indicating continued cycling over a 7-day interval. Thus, as CTLp
      frequencies remain fairly constant from 7 to 30 days after infection, the
      persistent increase (> 30x) in numbers must be accompanied by a very substantial
      loss of virus-specific CD8+ T cells.

PMID- 7561075
TI  - Induction of bcl-x by CD40 engagement rescues sIg-induced apoptosis in murine B
      cells.
AB  - CD40L, a membrane protein of activated T cells, interacts with the B cell
      receptor CD40. This interaction has been implicated in the rescue of germinal
      center B cells from apoptosis and in the rescue of WEHI-231 B lymphoma cells from
      sIg-induced apoptosis. In this report, we have demonstrated that the signal
      mediated by CD40L acts upon bcl-x, a bcl-2 homologue. bcl-x expression is
      strongly enhanced by CD40 receptor engagement, while there is little or no
      induction by sIg cross-linking. The expression of bax and bcl-2 is not
      significantly affected by either CD40L or sIg cross-linking. Antisense but not
      sense phosphorothioate oligonucleotide for bcl-x can partially block this CD40
      mediated apoptotic rescue. This result suggests that the up-regulation of bcl-x
      by CD40L plays an important role in CD40-mediated apoptotic rescue in murine B
      cells.

PMID- 7561076
TI  - T cell development in CD8-/- mice. Thymic positive selection is biased toward the
      helper phenotype.
AB  - The CD4 and CD8 molecules are involved in T cell differentiation and activation.
      Nevertheless, efficient thymic maturation of helper T cells has been shown in the
      absence of the CD4 molecule. These CD4-deficient helper T cells expressed alpha
      beta-TCR and were able to control Leishmania infections and to mediate Ab class
      switch. Using mice deficient for the CD8 alpha-chain, we investigated whether a
      similar cytotoxic T cell population was generated in the absence of the CD8
      coreceptor. A CD8-deficient cytotoxic T cell population corresponding to the
      described CD4-deficient helper T cell population was virtually absent both
      functionally and physically. These results support the idea that thymic
      maturation is asymmetrical and strongly biased toward the helper phenotype.

PMID- 7561078
TI  - Rapid rejection of H2k and H2k/b bone marrow cell grafts by CD8+ T cells and NK
      cells in irradiated mice.
AB  - Acute rejection of transplanted bone marrow cell (BMC) grafts can occur within 48
      h in unsensitized, lethally irradiated mice, and NK cells have been implicated as
      the effector cells. Recently, we observed that both CD8+ TCR-alpha beta+ T and NK
      cells of irradiated mice could rapidly reject allogeneic lymph node cell grafts.
      In this study, we evaluated the ability of NK and CD8+ T cells to mediate
      rejection of H2k or H2k/b BMC grafts by pretreating groups of mice with depleting
      mAbs. H2k BMC were transplanted into syngeneic, B6 (H2b), BALB/c (H2d), NZB
      (H2d), and (NZB x B6)F1 (NZB6F1, H2d/b) hosts. Proliferation measured 5 days
      after cell transfer indicated that syngeneic, B6, and BALB/c hosts accepted H2k
      BMC grafts. However, CD8+ T cells from NZB and poly I:C-treated BALB/c hosts, and
      NK cells from poly I:C-treated NZB6F1, hosts, rejected H2k BMC grafts. In NZB6F1
      hosts, there was an added effect of anti-TCR-alpha beta and anti-NK1.1 mAbs. It
      is possible that T and NK cells cooperate in rejecting H2k or H2k/b BMC grafts in
      certain hosts. Transplantation of H2k/b, but not H2k/d, BMC into similar
      recipients had the same fate as H2k BMC. Thus, certain CD8+ T cells may share a
      similar recognition system with NK cells.

PMID- 7561079
TI  - Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC
      class I presentation.
AB  - The effect on MHC class I Ag presentation of enhancing a protein's rate of
      degradation by the ubiquitin-proteasome pathway was investigated. In extracts of
      mouse B-lymphoblasts and reticulocytes, as in rabbit reticulocytes, proteins with
      acidic or basic N-termini are conjugated to ubiquitin and degraded by the 26S
      proteasome very rapidly. We found that the rate of MHC class I presentation of
      microinjected beta-galactosidase was enhanced when this antigenic protein was
      modified with such a destabilizing amino-terminal residue. This enhanced
      presentation was inhibited by blocking potential ubiquitination sites on the
      protein through methylation of amino groups and by peptide aldehyde inhibitors of
      the proteasome. Furthermore, in B lymphoblast cell extracts, the rapid
      degradation of these beta-galactosidase constructs required ATP and ubiquitin and
      was blocked by inhibitors of proteasomes. Their rates of degradation in extracts
      correlated with their rates of class I Ag presentation in vivo. These results
      indicate that ubiquitin conjugation is a key rate-limiting step in Ag
      presentation and provide further evidence for a critical role of ubiquitin and
      the 26S proteasome in generating MHC class I-presented peptides.

PMID- 7561077
TI  - B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells
      to protein antigens in vivo.
AB  - The potential role of different subsets of APCs to stimulate naive CD4+ T cells
      to peptide and protein Ags in vivo was examined. Mice lacking B cells (microMT
      knockout mice) were impaired in their priming to protein but not peptide Ags,
      suggesting a requirement for B cells in priming to protein Ags in vivo.
      Experiments designed to determine the ability of splenic dendritic cells (DCs)
      and B lymphocytes to take up peptide or protein Ags in vivo demonstrated that
      peptide Ags were taken up preferentially by DCs, whereas proteins were taken up
      by Ag-specific B cells in vivo. A further examination of the Ag-specific B cells
      pulsed in vivo with protein Ags revealed a marked up-regulation in surface
      expression of B7-2 costimulatory molecules, detectable as early as 4 h after Ag
      administration. Based on their potency in the uptake and processing of protein
      Ags as well as their ability to up-regulate costimulatory molecules through Ag
      internalization, we suggest that Ag-specific B cells will be an important APC in
      priming naive CD4+ T cells to protein Ags in vivo.

PMID- 7561080
TI  - The intracellular transport of MHC class II molecules in the absence of HLA-DM.
AB  - The HLA-DM alpha and HLA-DM beta genes encode a nonpolymorphic, class II-like
      molecule that functions by an as yet undefined mechanism in the assembly of
      processed antigen-HLA class II complexes. Mutant cells that fail to express HLA
      DM are deficient in Ag processing. We previously isolated a subcellular
      compartment in mouse B cells in which functional processed Ag-class II complexes
      are first formed, referred to as the peptide-loading compartment. Here, evidence
      is provided that HLA-DM resides in a subcellular compartment with the
      characteristics of a peptide-loading compartment in a human B lymphoblastoid cell
      line, but is not required for the intracellular transport of HLA-DR3 molecules to
      a corresponding compartment in HLA-DM-deficient cells. Thus, the primary defect
      in HLA-DM-deficient cells does not appear to be a failure in the intracellular
      trafficking of class II molecules.

PMID- 7561082
TI  - Structure of the N-linked oligosaccharides of MHC class I molecules from cells
      deficient in the antigenic peptide transporter. Implications for the site of
      peptide association.
AB  - Class I molecules are N-linked glycoproteins encoded by the MHC. They carry
      cytosolic protein-derived peptides to the cell surface, displaying them to enable
      immune surveillance of cellular processes. Peptides are delivered to class I
      molecules by the transporter associated with Ag processing (TAP). Peptide
      association is known to occur before exposure of class I molecules to the medial
      Golgi-processing enzyme alpha-mannosidase II, but there is limited information
      regarding the location or timing of peptide binding within the earlier regions of
      the endoplasmic reticulum (ER)-Golgi pathway. A reported association of newly
      synthesized class I molecules with the ER chaperonin calnexin raises the
      possibility of persistence of the monoglycosylated N-linked oligosaccharide (NLO)
      Glc1Man8GlcNAc2, known to be recognized by this lectin. To explore these matters,
      we determined the structure of the NLOs on the subset of newly synthesized class
      I molecules awaiting the loading of peptide. We pulse-labeled murine MHC H-2Db
      class I molecules in RMA/S cells, which lack one of the TAP subunits, causing the
      great majority of the molecules to be retained for prolonged periods in an early
      secretory compartment, awaiting peptide binding. MHC molecules pulse-labeled with
      [3H]glucosamine were isolated, the NLOs specifically released and structurally
      analyzed by a variety of techniques. Within the chosen window of biosynthetic
      time, most Db molecules from parental RMA cells carried mature NLOs of the
      biantennary complex-type, with one to two sialic acid residues. In RMA/S cells,
      such chains were in the minority, the majority consisting of the precursor forms
      Man8GlcNAc2 and Man9GlcNAc2. No glucosylated forms were detected, nor were the
      later processing intermediates Man5-7GlcNAc2 or GlcNAc1Man4-5GlcNAc2. Thus, most
      Db molecules in TAP-deficient cells are retained in an early compartment of the
      secretory pathway, before the point of first access to the Golgi alpha
      mannosidase I, which trims alpha 1-2 linked mannose residues, but beyond the
      point where the alpha 1-3-linked glucose residue is finally removed by the ER
      glucosidase II. Thus, structural analysis of NLOs on class I molecules within a
      defined biosynthetic window has established a biochemical measure of the timing
      of peptide association.

PMID- 7561081
TI  - The ligand-induced membrane IgM association with the cytoskeletal matrix of B
      cells is not mediated through the Ig alpha beta heterodimer.
AB  - The B cell Ag receptor complex consists of membrane-associated Ig (mIg), Ig
      alpha, and Ig beta, associated molecules that have been implicated in transducing
      the activation signal that occurs upon receptor cross-linking. The role of the Ig
      alpha beta heterodimer in mediating binding to the cytoskeleton is unknown. We
      studied the ligand-induced association of mIgM with the cytoskeleton following
      receptor cross-linking in mIgM-expressing B lymphoma lines by biochemical assays,
      FACS analysis, and electron microscopy. Cytoskeletal association is not detected
      in unstimulated cells, but occurs rapidly upon anti-IgM-mediated cross-linking.
      Ig alpha is absent from the cytoskeleton-mIgM complex. To further analyze the
      possible role of Ig alpha beta in cytoskeletal binding, a surface Ig alpha beta
      negative plasmacytoma line was transfected with a mutant form of mIgM (IgM-MutA).
      IgM-MutA is expressed on the surface despite the lack of Ig alpha beta, and the
      cytoskeletal binding occurred to a similar extent as in Ig-alpha-positive cell
      lines. In another transfectant expressing a mutated form of human mIgM (YS:VV),
      which does not have the capacity to bind to Ig alpha beta, the association of the
      receptor with the cytoskeleton appeared to be more extensive (100%) and faster
      than with mouse mIgM. These data indicate that Ig-associated Ig alpha beta
      proteins are not required for mIgM association with the cytoskeleton.

PMID- 7561083
TI  - Opposing effects of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells
      isolated from different mouse strains.
AB  - The development of naive dense CD4+ T cells from different mouse strains toward
      Th1 cells, as monitored by measuring secondary IFN-gamma production, was affected
      by TGF-beta 2 in a differential way. Th1 cell development of naive CD4+ T cells
      from strains C57Bl/6, BALB/c, and NMRI primed by immobilized anti-CD3 mAb was
      strongly inhibited in the presence of TGF-beta 2. Even when the Th1 cell-inducer
      IL-12 was added, the same effect of TGF-beta 2 was observed. In contrast, Th1
      development was substantially promoted by TGF-beta 2 with T cells from C3H/He and
      CBA/J mice. Further analyses using CD4+ T cells from (C57Bl/6xCBA/J)F1 hybrids or
      DBA/1 mice showed that Th1 development was inhibited by TGF-beta 2 if the T cells
      were activated by anti-CD3 mAb, but it was enhanced upon costimulation with anti
      CD28 mAb. Determination of primary IL-2 production revealed that T cells from
      (C57Bl/6xCBA/J)F1 and DBA/1 mice produced low amounts of IL-2 following
      stimulation by anti-CD3 mAb alone and comparatively high amounts after
      coactivation by anti-CD28 mAb. In the presence of TGF-beta 2, the production of
      IL-2 was completely suppressed if such T cells were activated solely by anti-CD3
      mAb, but it was only partially inhibited after costimulation by anti-CD28 mAb.
      Furthermore, TGF-beta 2-promoted Th1 development of such T cells was strongly
      inhibited after neutralization of endogenously produced IL-2 and completely
      restored by the addition of human IL-2. Thus, our results indicate that the TGF
      beta 2-mediated stimulation of Th1 cell development requires the presence of
      relatively high concentrations of IL-2. Therefore, the opposing effect of TGF
      beta 2 on the Th1 cell development of naive CD4+ T cells from different mouse
      strains appears to be the result of the variable potency of the respective CD4+ T
      cells to produce IL-2 in the presence of TGF-beta 2.

PMID- 7561084
TI  - T cell-dependent secretion of IL-1 beta by a dendritic cell line (XS52) derived
      from murine epidermis.
AB  - IL-1 beta has been reported to play an essential role in the induction of T cell
      mediated immune responses in skin, and Langerhans cells are considered to be the
      primary source of IL-1 beta in epidermis. We have established recently a long
      term dendritic cell line (XS52) from mouse epidermis. This line resembles
      resident epidermal Langerhans cells in many respects, including the potent
      capacity to present a protein Ag (KLH) to a CD4+ Th1 clone (HDK-1) and the
      expression of IL-1 beta mRNA. We sought to determine whether XS52 cells secrete
      IL-1 beta upon Ag-dependent interaction with T cells and, if so, to elucidate the
      mechanism. Despite constitutive expression of mRNA for both IL-1 beta and the IL
      1 beta-converting enzyme (ICE), XS52 cells secreted no detectable IL-1 beta
      spontaneously. When they were cultured with HDK-1 T cells and KLH, relatively
      large amounts of IL-1 beta (17.5-kDa form) were detected in the culture
      supernatant. IL-1 beta was secreted by LPS-stimulated XS52 cells, but not by LPS-
      or Con A-stimulated HDK-1 cells, suggesting that IL-1 beta is secreted primarily
      by XS52 cells in the coculture system. Incubation with HDK-1 cells alone or with
      KLH alone caused no IL-1 beta secretion, indicating the requirement for both T
      cells and Ag. IL-1 beta secretion was associated with a striking up-regulation of
      IL-1 beta mRNA and a modest up-regulation of ICE mRNA and enzymatic activity. IL
      1 beta secretion was blocked by Ac-YVAD-CHO (a peptide inhibitor of ICE), CTLA4
      Ig fusion protein, or anti-Ia mAb. IL-1 beta secretion was triggered in a T cell
      independent manner by either CTLA4-Ig or anti-Ia mAb in immobilized forms. Thus,
      the XS52 dendritic cell line secretes, by an ICE-dependent mechanism,
      biologically relevant amounts of IL-1 beta upon Ag-dependent interaction with T
      cells, with both Ia molecules and B7-related molecules playing essential roles.

PMID- 7561085
TI  - Effect of gene-targeted mutation in TNF receptor (p55) on contact
      hypersensitivity and ultraviolet B-induced immunosuppression.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic proinflammatory
      cytokine. TNF-alpha has been implicated in the pathogenesis of delayed-type
      hypersensitivity reactions such as allergic contact hypersensitivity and has been
      suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression.
      Conflicting reports, however, exist concerning the effects of TNF-alpha on
      contact hypersensitivity (CHS). To determine the role of TNF-alpha in the
      generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor
      (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNFB) to
      induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8
      +/- 20.9%, p < 0.025) compared with normal syngeneic mice (C57BL/6) assessed by
      ear swelling. To determine whether UVB can induce suppression in TNF-R1(-) mice,
      mice were irradiated on the shaved abdomen with 96 mj/cm2 UVB and 3 days later
      they were painted with 0.5% DNFB (sensitization dose), followed 5 days later with
      0.2% DNFB to the left ear (challenge dose). Significant suppression of CHS was
      observed both locally (sensitization on irradiated site) and systemically
      (sensitization on unirradiated site) in UVB-irradiated TNF-R1(-) mice as well as
      in normal mice. To rule out possible signaling through p75 TNF-R, the mice were
      treated with anti-TNF-alpha Ab (V1q), which can neutralize any TNF effects
      through either receptor. V1q had no effect on these phenomena observed in TNF-R1(
      ) mice. These results suggest that TNF-alpha plays a regulatory role in CHS but
      is not required to induce UVB-mediated immunosuppression.

PMID- 7561086
TI  - Intermediate steps in thymic positive selection. Generation of CD4-8+ T cells in
      culture from CD4+8+, CD4int8+, and CD4+8int thymocytes with up-regulated levels
      of TCR-CD3.
AB  - Minor thymus subpopulations representing possible intermediates in thymic
      positive selection were isolated by cell sorting from bcl-2 transgenic mice, and
      cultured 1 to 4 days in simple medium to assess their ability to spontaneously
      develop the surface phenotype of mature T cells. Recovery of cells was in the 60
      to 80% range, and no cell proliferation occurred. Only cells originally
      expressing high, near mature T cell levels of CD3 developed further in culture by
      down-regulation of CD4 or CD8. The main mature cell product was CD4-8+,
      regardless of whether the starting phenotype of the CD3high intermediates was
      CD4+8+, CD4int8+, or CD4+8int; only an intermediate subpopulation expressing the
      highest levels of CD4 (CD4high8int) produced a dominance of CD4+8- mature
      progeny. Partial down-regulation of CD8 was therefore not a good indicator of
      CD4+ T lineage commitment. These and previous results indicate that maturation to
      the CD8+ T lineage involves a rapid up-regulation of the TCR-CD3 complex, but a
      relatively slow down-regulation of CD4; it may also involve a partial, transient
      reduction in surface CD8. In contrast, maturation to the CD4+ T lineage involves
      a relatively rapid down-regulation of CD8, with maintenance of high levels of
      CD4. There appears to be a marked asymmetry in the developmental steps leading
      from CD4+8+ thymocytes to the CD8+ or to the CD4+ T cell lineage.

PMID- 7561087
TI  - Modulation of the Grb2-associated protein complex in human CD4+ T cells by
      receptor activation.
AB  - A panel of human CD4+ T cell clones was utilized to dissect and analyze the
      biochemical consequences of activation of CD3 or CD28. To molecularly
      characterize receptor-activated proximal signaling events, tyrosine
      phosphorylated proteins co-precipitating with a Grb2 fusion protein after
      receptor activation were analyzed. Ligation of CD28, but not other costimulatory
      molecules, induced the tyrosine phosphorylation of two previously identified Grb2
      binding proteins (pp76 and pp116). A third Grb2 binding protein (pp36) was
      extensively tyrosine phosphophorylated in response to combined CD3 and CD28
      activation, but not in response to ligation of either receptor alone. cAMP and co
      ligation of CD45 affected the receptor-activated tyrosine phosphorylation of Grb2
      associated proteins. Furthermore, we demonstrated that two signaling molecules,
      Vav and phosphatidylinositol 3'-kinase (PI(3)K), also interacted with the Grb2
      protein complex. The activity of PI(3)K was required for T cell activation,
      because wortmannin, a PI(3)K inhibitor, blocked T cell proliferation and cytokine
      production induced by ligation of CD3 and CD28. In conclusion, we demonstrate
      that in activated human T cell clones, the composition of Grb2 protein complex is
      modulated by costimulatory signals and cAMP, which may be important for the
      regulation of intracellular signal transduction.

PMID- 7561088
TI  - IFN-gamma receptor-deficient mice are hypersensitive to the anti-CD3-induced
      cytokine release syndrome and thymocyte apoptosis. Protective role of endogenous
      nitric oxide.
AB  - Mice with a disruption of the IFN-gamma receptor alpha-chain gene (IFN-gamma R
      alpha o/o mice) were found to be significantly more sensitive than their wild
      type counterparts to induction of the anti-CD3-induced disease syndrome.
      Specifically, when given a selected dose of anti-CD3 Ab, IFN-gamma R alpha o/o
      mice developed severe hypothermia and hypoglycemia, leading to 100% mortality
      within 72 h. In contrast, wild-type mice failed to develop overt pathologic
      manifestations and survived. Histologic examination revealed apoptosis in
      thymuses and spleens, which were significantly more pronounced in the mutant than
      in the wild-type mice, as confirmed by flow cytometric and DNA electrophoretic
      analysis. Apoptosis affected mainly CD4+CD8+ and CD4+CD8- thymocytes. Other
      histologic alterations were steatosis in livers, and erythrocyte extravasation
      and infiltration of apoptotic cells in lungs, all of which were exclusively
      observed in IFN-gamma R alpha o/o mice. Blood levels of TNF, IL-2, IL-6, and IL
      10 were slightly more elevated in IFN-gamma R alpha o/o mice, but insufficiently
      so to explain increased disease severity. Thus, even more elevated cytokine
      levels in wild-type mice receiving high doses of anti-CD3 Ab were not associated
      with morbidity or apoptosis. Blood levels of IFN-gamma were barely detectable in
      anti-CD3-challenged wild-type mice, but were relatively high in the mutant mice.
      Increased susceptibility of IFN-gamma R alpha o/o mice was associated with
      impaired nitric oxide (NO) production, as indicated by significantly lower plasma
      nitrite levels and by more transient expression of spleen inducible NO synthase
      mRNA. Moreover, treatment of wild-type mice with the NO synthase inhibitor N
      nitro-L-arginine methylester resulted in increased anti-CD3-induced morbidity and
      mortality. The data indicate that IFN-gamma R alpha o/o mice produce less NO and
      are therefore more sensitive than wild-type mice to the deleterious effect of
      anti-CD3 Ab.

PMID- 7561089
TI  - Modulation of anti-IgM-induced B cell apoptosis by Bcl-xL and CD40 in WEHI-231
      cells. Dissociation from cell cycle arrest and dependence on the avidity of the
      antibody-IgM receptor interaction.
AB  - The demise of B cell progenitors expressing functional IgM receptors for self
      appears to be the main mechanism by which B cell tolerance is accomplished. The
      genetic mechanisms that regulate the death process during this critical step of B
      cell development are still poorly understood. We have studied the regulation of
      apoptosis in WEHI-231 lymphoma cells after treatment with a panel of anti-IgM
      mAbs as an in vitro model of clonal B cell deletion. We showed that a product of
      bcl-x, Bcl-xL, can inhibit anti-IgM-induced apoptosis but not cell cycle arrest
      in a dose-dependent manner. Bcl-xL was efficient in protecting B cells from low
      but not high avidity anti-IgM mAbs. In contrast to that observed with Bcl-xL,
      CD40 stimulation was efficient in inhibiting both cell cycle arrest and apoptosis
      after IgM cross-linking regardless of the binding avidity of the anti-IgM Ab.
      Moreover, activation through IgM receptors but not CD40 induced up-regulation
      followed by rapid down-modulation of Bcl-xL. Thus, the capacity of Bcl-xL to
      modulate anti-IgM-induced apoptosis in WEHI-231 cells is highly dependent on the
      avidity of the Ab-IgM receptor interaction.

PMID- 7561090
TI  - Murine CD4+ T cells undergo TCR-activated adhesion to extracellular matrix
      proteins but not to nonantigenic MHC class II proteins.
AB  - Engagement of the TCR modulates the avidity of several receptors that play key
      roles in lymphocyte adhesion and/or signal transduction, including CD8,
      CD11a/CD18 (LFA-1), CD2, and several beta 1-integrins. Here, we investigated
      whether CD4+ T cells similarly undergo TCR-regulated adhesion to isolated MHC
      class II proteins through CD4. Strong adhesion of a number of CD4+ T cell clones
      to immobilized antigenic peptide/class II complexes was readily detectable.
      Adhesion to antigenic class II proteins was CD4 dependent and inhibited by
      pretreatment of T cells with the protein tyrosine kinase inhibitor herbimycin A,
      suggesting that adhesion requires TCR- and/or CD4-derived signal transduction.
      Treatment of T cells with anti-TCR Ab strongly increased subsequent adhesion to
      the extracellular matrix proteins, fibronectin and vitronectin, but,
      significantly, not to immobilized nonantigenic class II proteins. Suboptimal
      densities of antigenic peptide/class II complexes also activated adhesion of T
      cells to coimmobilized fibronectin or vitronectin, and this resulted in
      production of IFN-gamma to levels exceeding those stimulated by optimal densities
      of antigenic class II complexes alone. However, no augmentation of adhesion or
      cytokine secretion occurred when self or third party class II proteins were
      coimmobilized with antigenic class II complexes. The present results, therefore,
      suggest fundamental differences in the mechanism by which the TCR regulates
      coreceptor adhesion in CD4+ and CD8+ T cells.

PMID- 7561091
TI  - Alloreactive gamma delta thymocytes utilize distinct costimulatory signals from
      peripheral T cells.
AB  - Interactions between CD28/CTLA-4 on T cells and CD80 (B7.1) and CD86 (B7.2)
      counter receptors provide crucial costimulatory signals for TCR-alpha beta+
      lymphocytes. To test the role of CD28 in thymic development and activation of TCR
      gamma delta+ T cells, we introduced the alloreactive V gamma 2V alpha 11.3 TCR
      into CD28-deficient mice (CD28-/-). We show that positive and negative selection
      of gamma delta Tg thymocytes proceeded normally in the absence of CD28. Although
      mature Tg gamma delta+ thymocytes required a second costimulatory signal for
      proliferation, gamma delta+ thymocytes from CD28-/- and CD28+/- littermates
      responded equally well to the alloantigen Tlab. Alloreactivity of CD28-/- and
      CD28+/- Tg gamma delta+ thymocytes could not be blocked with mAbs against CD80
      and CD86 ligands. Thus gamma delta thymocytes utilize a costimulatory system
      during development and alloresponses that is independent of CD28/CD80 and
      CD28/CD86 interactions. By contrast to V gamma 2V alpha 11.3+ thymocytes,
      alloreactivity of V gamma 2V alpha 11.3+ lymph node T cells depended on CD28
      costimulation and was severely impaired in CD28-/- mice. These data provide
      functional evidence that maturation and selection of gamma delta cells is
      independent of CD28. These results also indicate that distinct costimulatory
      pathways are operational in mature thymocytes and peripheral T cells.

PMID- 7561092
TI  - Inhibition of T cell costimulation by VCAM-1 prevents murine graft-versus-host
      disease across minor histocompatibility barriers.
AB  - Activation of T cells leading to graft-vs-host disease (GVHD) requires two
      signaling events: the Ag-specific signal generated through the engagement of the
      TCR/CD3 complex with antigenic peptide fragments presented by MHC molecules on
      APCs and the second signal provided through additional costimulatory ligands. T
      cells have preferential costimulatory requirements depending on their state of
      activation-induced maturation. In the present study, we investigated the role of
      the receptor-ligand pair VLA-4 (alpha 4 beta 1) and VCAM-1 in allogeneic T cell
      responses in vitro and in vivo. Anti-VCAM-1 mAb effectively inhibited mixed
      lymphocyte culture (MLC) across several major MHC barriers and secondary MLC
      across minor histocompatibility Ags (95.5% and 90.0% inhibition, respectively).
      In contrast, anti-VLA-4 mAb inhibited a CD8(+)-mediated primed CTL response in
      vitro by 100%, yet had little effect on proliferative responses. In the
      B10.D2/nSnJ-->BALB/c (both H-2d) system of GVHD, BALB/c received anti-VCAM-1, or
      anti-VLA-4 or controls NS-1 or Y13-259 for the first 5 wk after transplant. Anti
      VLA-4 mAb delayed the onset of GVHD, but failed to reduce incidence, severity or
      GVHD-related mortality. In contrast, anti-VCAM-1 reduced the incidence of GVHD
      from 100% (18/18) in control animals to 53.3% (8/15) (p < 0.01) on day 70 post
      transplant and significantly decreased GVHD-related mortality. Sixty percent
      (9/15) of anti-VCAM-1 recipients survived more than 180 days after transplant.
      Long-term engraftment of allogeneic bone marrow was documented in all
      transplanted mice by PCR analysis of a microsatellite region in the IL-1 beta
      gene.

PMID- 7561093
TI  - Antigen-presenting cells for naive transgenic gamma delta T cells. Potent
      activation by activated alpha beta T cells.
AB  - The function of gamma delta T cells, particularly the minor population of
      circulating gamma delta T cells, remains unclear. To study these lymphoid gamma
      delta T cells, a transgenic SCID mouse containing the KN6 gamma delta TCR whose
      ligand is the TL gene product, T22b, was created. KN6-SCID mice contain a
      monoclonal population of naive KN6+ gamma delta T cells. Using these mice, we
      have studied the APC required for activation of KN6+ gamma delta T cells in vitro
      and in vivo. Analysis of an in vitro mixed lymphocyte response identified a
      hierarchy of potency for stimulation: dendritic cells = T cell blasts > B cell
      blasts > B cells > resting T cells. In contrast, in vivo, only alpha beta T cells
      fully activated KN6+ gamma delta T cells as measured by an increase in the number
      of splenic KN6+ cells, the development of blast morphology, and the development
      of proliferative anergy in the responding KN6+ cells. The strong stimulatory
      properties of C57BL/6J T cells appeared to depend on their having been activated
      by KN6-SCID alloantigens. T cells from (C57BL/6J x BALB/c)F1 mice, which are
      tolerant of KN6-SCID alloantigens, could not fully activate KN6+ cells. However,
      the F1 T cells could activate KN6+ cells if they were activated in vivo by the
      mitogen, staphylococcal enterotoxin B. A mixture of third party activated T cells
      plus T22b+ non-T cells only partially activated KN6+ cells, implying that
      activated T22b+ T cells are acting directly as stimulatory cells. Although the
      Ags recognized by gamma delta T cells are generally unknown, Ag presentation by
      activated alpha beta T cells may be an important method of activation.

PMID- 7561094
TI  - Alpha and beta chemokines induce NK cell migration and enhance NK-mediated
      cytolysis.
AB  - Chemokines have been shown to play an important role in both the adhesion and
      migration of numerous leukocytic cell types, including granulocytes, monocytes,
      mast cells, and T lymphocytes. However, the biologic effects of chemokines on NK
      cells remain to be defined. Chemotaxis studies using purified human NK cells and
      a panel of human recombinant chemokines revealed that macrophage inflammatory
      protein (MIP)-1 alpha and IFN-inducible protein-10 (IP-10) are potent NK cell
      chemoattractants in vitro. Modest but significant chemotactic (not chemokinetic)
      responses were also observed in response to RANTES, MCP-1, MCP-2, MCP-3, and MIP
      1 beta. Chemokine receptor expression on human NK cells was determined through
      displacement and Scatchard analyses, using a panel of radiolabeled chemokines,
      and revealed the presence of both distinct and shared chemokine receptors with
      affinities similar to those previously described for other cell types. Functional
      studies have also revealed that the beta chemokines and IP-10 are capable of
      augmenting NK- but not LAK- or ADCC-specific cytolytic responses in both a dose-
      and donor-dependent fashion. Neutralization analysis using Abs specific for
      various adhesion molecules revealed that NK:tumor cell conjugate formation is
      required for chemokine-induced NK killing. In addition, NK cells incubated in the
      presence of beta chemokines and IP-10 for 4 h induced the release of granule
      derived serine esterases, suggesting a possible mechanism for chemokine-mediated
      NK killing. These results suggest that chemokines not only play an important role
      in the recruitment of NK cells, but also may be important mediators of NK cell
      degranulation augmenting local tumor cell destruction.

PMID- 7561095
TI  - Characteristics of ATP-dependent peptide transport in isolated microsomes.
AB  - This report examines the transport properties and specificity of ATP-dependent
      peptide transport by the murine transporter for Ag presentation (TAP) complex in
      isolated microsome preparations from H-2d haplotype mice. The murine TAP complex
      has a Km of 661 nM and a maximum velocity of 2.9 fmol/min.micrograms microsome
      protein for a modified peptide corresponding to a defined MHC class I binding
      epitope from influenza nucleoprotein recognized by CD8+ CTL in association with
      the Kd molecule. This high Km value for peptide transport suggests that the rate
      and efficiency of peptide transport of the TAP complex are influenced by the
      concentration of processed peptides derived from self and foreign proteins in the
      cell cytoplasm. Furthermore, these findings imply that competition among peptides
      for TAP-dependent transport is unlikely to be an important factor in determining
      the immunodominance of certain peptide epitopes within a foreign protein
      recognized by CD8+ T lymphocytes. We also examined the specificity of TAP
      transport for peptides containing bona fide murine MHC class I binding epitopes
      and provide evidence that certain flanking residues can affect the efficiency of
      peptide epitope transport by the TAP complex.

PMID- 7561096
TI  - In vitro priming of tumor-reactive cytolytic T lymphocytes by combining IL-10
      with B7-CD28 costimulation.
AB  - Naive spleen cells from syngeneic mice generated tumor-reactive CTL following
      three cycles of in vitro culturing with IL-10 and cells from the P815 mouse
      mastocytoma that expressed the B7-1 or B7-2 costimulator. Unpurified as well as
      CD8-enriched naive splenocytes could be used for priming. The in vitro primed CTL
      were CD8+, and their recognition was MHC class I restricted. Both IL-10 and B7
      transfected P815 cells were required for the priming. However, a combination of
      exogenous IL-10 and IL-2 in the presence of B7-negative wild-type P815 cells also
      induced tumor-reactive CTL. Injection of the neutralizing anti-IL-10 mAb JES-2A5
      into mice reduced their ability to mount a primary CTL response after
      immunization with B7-1+ P815 cells, and inclusion of this mAb in the in vitro
      cultures inhibited a secondary CTL response. Adoptive transfer of the in vitro
      primed CTL had a therapeutic effect in mice with P815 established as an ascites
      tumor. Our results underscore an important role of IL-10 in the induction of a
      tumor-specific CTL response.

PMID- 7561097
TI  - Costimulation of human CD4+ T cells by fibroblast growth factor-1 (acidic
      fibroblast growth factor).
AB  - T cell infiltration is prevalent in wound healing, atherosclerosis, vascular
      lesions in chronic allograft rejection, and autoimmune diseases. Whether T cells
      play a role in the migration and proliferation of vascular smooth muscle cells
      and endothelial cells in these lesions is not known. We previously reported that
      some human T cells express FGF-1, a potent growth factor for vascular smooth
      muscle cells and endothelial cells. In this study, we extend this observation and
      examine the expression and function of FGF receptors on human T cells. Using
      reverse transcription-PCR, Northern analysis, and immunohistochemistry, we found
      that some human T cells also express high affinity FGF receptor 1 (FGFR-1)
      respond to FGF-1. In the presence of anti-CD3, exogenous FGF-1 functions as a
      costimulator for these T cells, while FGF-1 alone does not induce T cell
      proliferation. [3H]Thymidine incorporation is sevenfold higher in T cells
      costimulated with FGF-1 compared with stimulation with anti-CD3 alone. Using
      limiting dilution, we demonstrate that FGF-responsive T cells are present in
      normal peripheral blood at a mean frequency of 1:19780 (95% confidence limits,
      1:15100-1:23000), and similar T cells are increased in the peripheral blood of
      heart transplant recipients (mean frequency, 1:4210; 95% confidence limits,
      1:3420-1:6781). In addition, a subline of Jurkat, a human T cell tumor, expresses
      FGFR-1 receptor. The function of FGFR-1 receptor in Jurkat T cells is
      demonstrated by the production of IL-2 after stimulation with FGF-1 and anti-CD3.
      IL-2 levels are sevenfold higher in Jurkat T cells costimulated with FGF-1
      compared with those stimulated with anti-CD3 alone. FGF-1 alone has no effect on
      Jurkat T cells. These findings thus provide evidence that a subset of human T
      cells expresses a receptor for vascular cell growth factors, and this receptor
      functions to increase IL-2 production consistent with costimulation. The
      potential role of FGF-responsive T cells in a variety of vascular and
      inflammatory lesions is discussed.

PMID- 7561098
TI  - Diverse VH and V kappa genes encode antibodies to Pseudomonas aeruginosa LPS.
AB  - The molecular nature of the murine Ab response to Pseudomonas aeruginosa LPS was
      examined using a panel of 10 well-defined anti-LPS mAbs. Abs to P. aeruginosa LPS
      are encoded by diverse V-genes, with at least five VH and four V kappa gene
      families represented in these Abs. The Abs that bind to hydrophilic O
      polysaccharide side chains of B-band LPS and A-band LPS are encoded by VH J558,
      SM7, and J606 gene families, while Abs to hydrophobic core and lipid A regions
      are encoded by X24, SM7, and Q52 gene families. All active JH and only two J
      kappa (J kappa 2 and J kappa 5) germ-line genes are utilized in the anti-LPS Abs
      examined. Four of six anti-P. aeruginosa mAbs used diversity genes of the DSP2
      gene family. Interestingly, JH1 and JH2 use was observed in three mAbs that
      reacted with hydrophilic LPS epitopes (O-polysaccharide, A-band LPS), whereas JH3
      and JH4 use was observed in three mAbs that bound to the more hydrophobic regions
      of LPS (core, lipid A). Point mutations were observed in framework and
      complementarity-determining regions (CDRs) of VH and VL genes, suggesting an Ag
      driven maturation process in response to P. aeruginosa LPS. Mutations occurred in
      all heavy chain CDRs, as well as in CDR1 and CDR3 of the light chain, indicating
      an important role of these regions in binding to LPS. These data suggest that
      diverse VH and V kappa genes encode Abs to LPS from P. aeruginosa.

PMID- 7561099
TI  - Diversity of Ig light chain clusters in the sandbar shark (Carcharhinus
      plumbeus).
AB  - The genes encoding Ig chains in elasmobranchs are arranged in clusters or
      cassettes, an organizational pattern dramatically different from the mammalian
      translocon gene arrangement. Cluster gene arrangements, which have now been found
      in non-elasmobranchs as well, pose interesting dilemmas for understanding the
      mechanisms of Ig gene expression and regulation in terms of allelic exclusion and
      clonal selection. We have sequenced five lambda genomic clones encoding complete
      sandbar shark (Carcharhinus plumbeus) lambda L chain gene loci. While the coding
      regions among all five clones are highly homologous, the noncoding regions have
      significant differences that allowed us to identify two types of lambda L chain
      clusters. The noncoding regions are < 60% identical between groups, while the
      three clones belonging to the first group share > 95% identity in their noncoding
      regions. The second group is more diverse and may be comprised of several related
      subgroups. The two clones in this group share approximately 85% identity in the
      noncoding regions. Variations in the promoter region, including octamer and TATA
      box orientation and position, are identified between the two groups and may have
      implications for the molecular regulation of Ab production. Our results show the
      sandbar shark lambda L chain family to be a complex and diverse system.

PMID- 7561101
TI  - N-terminal and central regions of the human CD44 extracellular domain participate
      in cell surface hyaluronan binding.
AB  - CD44 molecules are cell surface receptors for hyaluronan (HA). To define regions
      of the extracellular domain of CD44 that are important for HA binding, we have
      studied the ability of HA-blocking CD44 mAbs to bind to CD44 from a variety of
      sources. Five CD44 mAbs (5F12, BRIC235, 3F12, BU-75, and HP2/9) of 21 studied
      were identified that at least partially blocked FITC-labeled HA (HA-FITC) binding
      to the standard form of CD44 (CD44S) in CD44-transfected Jurkat cells. Analysis
      of reactivity of HA-blocking CD44 mAbs defined three distinct epitopes. Lack of
      reactivity of mAb 5F12 with a CD44 fusion protein (CD44-Rg) containing an N
      terminal truncation of 20 amino acids (aa), as well as reactivity of mAb 5F12
      with an N-terminal CD44 synthetic peptide (CD44-9A), demonstrated that the N
      terminal proximal region of CD44 (aa 1 to 20) was involved in mAb 5F12 binding. A
      mutant cell line, CEM-NKR, derived from the T-ALL cell line, CEM, did not bind
      mAb 5F12 nor bind HA, whereas wild-type CEM did bind mAb 5F12 and HA. Sequence
      analysis of wild-type CEM and CEM-NKR CD44 cDNA demonstrated a G to A point
      mutation at position 575 in the CD44 cDNA of CEM-NKR, resulting in an arginine to
      histidine mutation at aa position 154. Taken together, our studies demonstrated
      that there are three epitopes to which HA-blocking mAbs bind in the extracellular
      domain of CD44, and that the CD44 N-terminal proximal and central regions are two
      regions in the extracellular domain of CD44 that may interact and either mediate
      or regulate HA binding to cell surface CD44.

PMID- 7561100
TI  - Analysis of CD2 and TCR-beta gene expression in Jurkat cell mutants suggests a
      cis regulation of gene transcription.
AB  - Thirty CD2- J32 stable clones, derived by mutagenesis and subsequent
      immunoselection with anti-CD2 Ab, were used to study the regulation of CD2 and
      TCR gene expression. Analysis of RNA expression revealed that the loss of surface
      expression of CD2 was due to a lack of expression of CD2 mRNA and was associated
      with a lack of expression of VDJ TCR-beta transcripts in 12 of these mutants,
      sparing the expression of DJ TCR-beta, TCR-alpha, CD3 gamma, delta, epsilon, and
      zeta RNA. The expression of other differentiation molecules was unaffected,
      except for CD1, CD4, and CD5, which were either decreased or absent in most of
      these mutants. A gain in the expression of TCR-gamma transcripts was observed in
      each of these mutants, while, as expected, no TCR-gamma transcripts were detected
      in wild-type J32 cells. Several mutants were able to use the human CD2 enhancer
      and the murine TCR-beta enhancer and promoter to activate transcription from
      reporter genes in the context of heterologous promoters, indicating that the
      mutation(s) does not affect transcription pathways. Consistent with this finding
      is the adequate expression in these mutants of several lineage-specific
      transcription factors. The expression of CD2 in several of these mutants was
      rescued by gene transfer using a genomic 28.5-kb CD2 fragment, suggesting that
      the enhancer function of this gene may be dependent on the enhancer site. These
      observations suggest that the coordinate expressions of CD2 and TCR-beta genes
      share common regulatory mechanisms involving factors regulating chromatin
      structure and accessibility.

PMID- 7561102
TI  - Comparative sequence analysis of cytokine genes from human and nonhuman primates.
AB  - Two major issues severely limit the studies of human recombinant cytokines/growth
      factors in nonhuman primates. First, assays and reagents specific for the
      detection and quantitation of human cytokines do not all function when utilized
      to detect/quantitate the nonhuman primate cytokines. Second, although most of the
      human cytokines appear to induce similar, if not identical, biologic function
      when used with cells from nonhuman primates in vitro or in vivo, they invariably
      induce Ab responses in vivo, precluding their repeated and/or continued use in
      vivo. Our laboratory has thus initiated studies to clone, sequence, and prepare
      recombinant cytokines from nonhuman primates and to define assays and reagents
      for their detection and quantitation at the nucleic acid and protein level. The
      data that were derived from such studies show that the nonhuman primate cytokines
      IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 alpha, IL-12
      beta, IL-15, IFN-alpha, IFN-gamma, and TNF-alpha share 93 to 99% homology at the
      nucleic acid and protein level with the human equivalents. The most prominent
      differences between human and nonhuman primate cytokine sequences were noted for
      IL-1 alpha/beta, IL-2, IL-8, IFN-alpha, IFN-gamma, and IL-12 beta. The aligned
      sequences of cytokines for human and several nonhuman primate species are
      provided herein, and a phylogenetic analysis of the published sequences of select
      cytokines from other species, along with those of the nonhuman primates, are
      described. In addition, comparative analysis of the relative bioactivity of our
      immunoaffinity-purified recombinant rhesus macaque IL-4, IL-15, and IFN-gamma
      with commercially available human recombinant cytokines is described herein.

PMID- 7561104
TI  - Characterization of herpes simplex virus type-1 infection and herpetic stromal
      keratitis development in IFN-gamma knockout mice.
AB  - Herpetic stromal keratitis (HSK) has an immune-mediated pathogenesis that
      involves T cells that have a type 1 cytokine profile. IFN-gamma is suspected to
      be the type 1 cytokine involved in ocular pathology, and to test this notion more
      directly the pathogenesis of HSK was compared in mice deficient in the IFN-gamma
      gene (gamma knockout or gko) and control mice (wild-type littermates or BALB/c
      mice). The clinical course of HSK in gko mice closely paralleled that in control
      mice, yet virus persisted in the corneas of gko mice for an extended period of
      time, severe periocular skin lesions developed, and gko mice were far more
      susceptible to encephalitis. Delayed-type hypersensitivity to viral Ag was
      present, though diminished, in knockout mice, and serum herpes simplex virus
      specific IgG isotypes indicated a Th2 shift. No differences existed in
      proliferative responses to in vitro Ag stimulation in gko vs control mice nor in
      T cell or proinflammatory cytokine mRNA levels in the corneas of infected mice.
      However, up-regulation of Th2 cytokine mRNA did occur in in vitro Ag-stimulated
      gko immune splenocytes. Histopathologic lesions were not statistically different
      between any of the groups of mice analyzed. These observations indicate that
      although IFN-gamma plays an important role in the clearance of virus from the
      eye, the pathogenesis of HSK lesions most likely involves additional cytokines,
      inflammatory mechanisms, or immune responses to nonviral Ags.

PMID- 7561105
TI  - Binding of FimD on Bordetella pertussis to very late antigen-5 on monocytes
      activates complement receptor type 3 via protein tyrosine kinases.
AB  - Nonopsonized Bordetella pertussis bind to human monocytes by means of the
      virulence factors filamentous hemagglutinin (FHA), pertactin, and the minor
      fimbrial subunit FimD. Receptors on monocytes that mediate binding of B.
      pertussis to these cells include complement receptor type 3 (CR3), which binds to
      FHA of B. pertussis, and very late antigen-5 (VLA-5), which binds to an, as yet,
      unknown ligand on these bacteria. In the present study, the possibility that FimD
      acts as a ligand for VLA-5 was investigated. Soluble fibronectin, which is the
      natural ligand for VLA-5, or mAbs against VLA-5 inhibited binding to monocytes of
      B. pertussis strains that express FimD but not of mutant strains that lack FimD.
      Beads that were coated with the fusion protein maltose-binding protein-FimD bound
      to adherent monocytes, and this binding was inhibited by soluble fibronectin or
      mAb against the alpha- or beta-chain of VLA-5, while soluble collagen or mAb
      against VLA-4, VLA-6, CR3, or HLA class II had no effect. Down-modulation of VLA
      5 on the apical surface of monocytes by plating the cells onto surfaces precoated
      with anti-VLA-5 mAb also inhibited binding of beads coated with maltose-binding
      protein-FimD to monocytes, while precoating of the surfaces with mAb against VLA
      6 or CR3 had no effect. These results indicate that VLA-5 on monocytes serves as
      a receptor for FimD on B. pertussis. Binding of C3bi-coated erythrocytes to
      monocytes, which is a measure of the binding activity of CR3, was enhanced when
      monocytes were adhered onto plates precoated with purified fimbriae of B.
      pertussis, while precoating with fimbriae lacking FimD had no effect. Precoating
      of the plates with FimD-containing fimbriae also enhanced binding of B.
      pertussis, which express FHA, but not of strains that lack FHA, to monocytes. The
      enhanced binding of C3bi-coated erythrocytes and B. pertussis to monocytes could
      be markedly inhibited by tyrphostin-47, a protein tyrosine kinase inhibitor.
      These results demonstrate that interaction of FimD of B. pertussis with VLA-5 on
      monocytes activates CR3, which requires protein tyrosine kinases and results in
      enhanced binding of B. pertussis to the latter receptor via FHA.

PMID- 7561103
TI  - Cytokine and nitric oxide regulation of the immunosuppression in Trypanosoma
      cruzi infection.
AB  - An intense suppression of splenic T cell proliferation to mitogens and to Ags
      from the parasite is characteristic of the acute phase of Trypanosoma cruzi
      infection in mice. The impairment of proliferation is coincident with high levels
      of IFN-gamma and nitrite and decreased production of IL-2 in the supernatants of
      spleen cell cultures from infected mice. Previous work demonstrated that
      suppression of proliferation is largely mediated by the population of adherent
      cells in the infected spleen. In this study we confirmed the active suppression
      exerted by these cells on Con A, anti-CD3, and parasite Ag-stimulated
      proliferation of CD4+ splenic T cells. Inasmuch as the high production of IFN
      gamma and of nitrite were compatible with intense macrophage activation and
      nitric oxide (NO) production, we determined the effects of cytokines that
      regulate macrophage activation and of NO on the proliferation of spleen cells
      from infected mice. We show that spleen cell proliferation to Ag and to T cell
      polyclonal stimuli is increased by neutralizing mAbs to IFN-gamma, TNF-alpha and 
      beta, or by the inhibitor of NO synthase, NG-monomethyl-L-arginine, added to the
      cultures. The addition of rIL-2 or rIL-4 also contributed to suppression
      reversal, and the combined addition of rIL-2 and anti-IFN-gamma mAb further
      increased lymphocyte proliferation. Anti-IL-4, anti-IL-10, or anti-TGF-beta
      neutralizing mAbs did not modify suppressed proliferative responses, and the
      addition of rIL-10 or of rTGF-beta also did not recover cell proliferation. Thus,
      the suppression of proliferative responses in T. cruzi-infected mice resulted
      largely from increased NO production by macrophages activated by IFN-gamma and
      TNF allied to insufficient IL-2 to fully support in vitro growth of T
      lymphocytes.

PMID- 7561106
TI  - A nonlethal rat parvovirus infection suppresses rat T lymphocyte effector
      functions.
AB  - Inoculation of the UMass strain of rat virus (RV-UMass) into adult
      immunocompetent rats results in a prolonged subclinical infection that is
      resolved in 4 to 8 wk. Co-labeling studies, using in situ hybridization (ISH) and
      immunohistochemistry (IHC), confirmed that RV-UMass was lymphocytotropic and
      capable of infecting CD4+ and CD8+ T cells as well as B cells. ISH studies also
      revealed that virus replication was restricted in unstimulated cells but was
      productive in concanavalin A-stimulated lymphocytes. A corollary of productive
      infection of lymphocytes was the suppression of lymphocyte functions. Although RV
      UMass did not appear to induce phenotypic changes during the course of infection,
      cells from infected rats had diminished proliferation and cytolytic responses.
      Both peripheral and mesenteric lymph node cells exhibited only partial recovery
      of their proliferative and cytolytic capacities one month after infection.
      Furthermore, RV-UMass-infected tissue culture maintained alloreactive CD4+ T
      cells in vitro, and a nonlethal infection of this T cell line inhibited Ag- and
      IL-2-induced proliferation. Because parvoviruses are widespread among laboratory
      rodents, these findings emphasize the importance of identifying and excluding
      parvovirus infection in rodents and in cultures of rat T lymphocytes.

PMID- 7561107
TI  - Cytotoxic T lymphocytes after oral immunization with attenuated vaccine strains
      of Salmonella typhi in humans.
AB  - Not only viruses, but certain parasites and bacteria as well, can elicit CTL
      involved in mediating protection. It has been surmised that CTL able to lyse
      Salmonella typhi-infected cells are likely to be important in protecting against
      S. typhi, an intracellular bacterial infection, but heretofore this has not been
      demonstrated. Consequently, the presence of CTL activity against S. typhi
      infected cells was investigated in human volunteers immunized with attenuated
      vaccine strains of S. typhi. Oral immunization with S. typhi strain CVD 908
      elicited circulating CTL effector cells capable of killing S. typhi-infected
      autologous EBV-transformed cells. CTL activity was observed after 6 to 8 days of
      in vitro expansion in the presence of S. typhi-infected autologous EBV
      transformed cells. Maximum CTL activity was observed 29 days after immunization.
      Depletion of CD8+ T cells eliminated or markedly reduced the CTL activity, while
      depletion of CD4+ T cells did not affect CTL responses. CTL activity was blocked
      by mAbs to human class I MHC Ags, but not by mAbs to class II MHC Ags. This first
      demonstration that oral immunization of volunteers with attenuated S. typhi
      elicits CD8+ T cell, MHC class I-restricted, CTL responses raises the possibility
      that CTL activity might play a significant role in protection during typhoid
      fever. It also encourages the future use of such attenuated strains as liver
      vector vaccines to stimulate specific CTL against relevant foreign Ags.

PMID- 7561108
TI  - Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen-activated
      protein kinases p44, p42, and p41 in vascular endothelial cells in a soluble CD14
      dependent manner. Role of protein tyrosine phosphorylation in lipopolysaccharide
      induced stimulation of endothelial cells.
AB  - Vascular endothelial cell (EC) injury or activation by LPS plays a critical role
      in the pathogenesis of Gram-negative meningitis and endotoxic shock. EC do not
      express membrane CD14, but respond to LPS in a soluble CD14-dependent manner. The
      signal transduction mechanisms involved in LPS-induced EC responses are largely
      unknown. We used bovine and human brain microvessel EC (BBMEC, and HBMEC) to
      study LPS-induced protein tyrosine phosphorylation. LPS rapidly induced the
      tyrosine phosphorylation of several proteins in BBMEC and HBMEC, which was
      detectable by 5 to 15 min, reached a maximum by 30 min, and declined by 60 to 90
      min. The increase in tyrosine phosphorylation was apparent following stimulation
      with LPS at 0.1 ng/ml and was dose dependent up to 100 ng/ml. Similar changes in
      tyrosine phosphorylation were induced by smooth and rough LPS as well as lipid A,
      but not by the inactive lipid A analogue, Rhodopseudomonas sphaeroides
      diphosphoryl lipid A. Pretreatment of EC with the tyrosine kinase inhibitor,
      herbimycin A, inhibited LPS-stimulated protein tyrosine phosphorylation and LPS
      mediated lactic dehydrogenase release from BBMEC and IL-6 release from HBMEC in a
      dose-dependent manner. Three proteins with apparent m.w. of 44, 42, and 41 kDa
      were predominant among the LPS-induced tyrosine phosphoproteins, and they were
      identified as mitogen-activated protein kinase isoforms ERK1, ERK2, and p38,
      respectively. LPS-induced protein tyrosine phosphorylation in HBMEC and BBMEC was
      soluble CD14 dependent, since pretreatment of these cells with anti-hCD14 mAb
      inhibited the LPS-induced tyrosine phosphorylation of p44, p42, and p41.
      Additionally, LPS induced a mobility shift in p44 and p42 mitogen-activated
      protein kinase isozymes, which was inhibited by herbimycin A pretreatment of the
      EC. These findings demonstrate for the first time that increased protein tyrosine
      phosphorylation and activation of mitogen-activated protein kinases occur rapidly
      after LPS stimulation of EC in the presence of soluble CD14. Our data also
      suggest that a herbimycin-sensitive step, presumably a tyrosine kinase, is
      involved in mediating LPS-induced human EC activation and IL-6 secretion.

PMID- 7561109
TI  - Serum amyloid A induces calcium mobilization and chemotaxis of human monocytes by
      activating a pertussis toxin-sensitive signaling pathway.
AB  - We have previously reported that serum amyloid A (SAA) induces adhesion and
      chemotaxis of human monocytes and polymorphonuclear neutrophils, in vitro as well
      as in vivo. Since the mechanism of SAA signaling is unknown, we have investigated
      the possibility that SAA, like other chemoattractants such as the chemotactic
      peptide FMLP and chemokines, might induce migration of monocytes by G protein
      activation. We report here that preincubation of monocytes with pertussis toxin
      (PTx) inhibited SAA chemotaxis, while incubation with cholera toxin (CTx) did
      not. Staurosporine and H-7, both inhibitors of protein kinase C (PKC),
      significantly decreased rSAA-induced chemotaxis of monocytes, suggesting that PKC
      may be involved in the rSAA signaling pathway. Moreover, rSAA, at concentrations
      that were effective in chemoattracting monocytes, resulted in transient elevation
      of cytoplasmic calcium concentration ([Ca2+]i), and incubation of cells with PTx
      markedly inhibited the mobilization of Ca2+ in response to rSAA. This suggests
      that both chemotaxis and the rise in [Ca2+]i, are mediated by G proteins of the
      Gi class. The increase in [Ca2+]i, induced in monocytes by rSAA, was comparable
      to that elicited by FMLP, and was severalfold greater than that induced by
      optimal concentrations of chemokine beta-family members such as RANTES, MCAF/MCP
      1, and MIP-1 alpha. The chemoattractants FMLP, RANTES, MIP-1 alpha, and MCAF/MCP
      1, all failed to desensitize rSAA-induced Ca2+ influx and chemotaxis in
      monocytes. This suggests that SAA uses a distinct receptor that is coupled to PTx
      sensitive G proteins.

PMID- 7561110
TI  - Sialyl Lewis(x) oligosaccharide reduces ischemia-reperfusion injury in the rabbit
      ear.
AB  - Ischemia-reperfusion injury in the rabbit ear is neutrophil (PMN)-mediated, and
      is significantly reduced by anti-adhesion agents directed against beta 2
      integrins, P-selectin, or L-selectin. We further examined selectin-mediated
      adherence in this setting following the administration of soluble sialyl Lewis(x)
      (SLe(x)), the principal carbohydrate ligand for P-, L-, and E-selectin, at
      various times following reperfusion. Under constant ambient temperature
      conditions, the rabbit ear vascular supply was isolated and occluded with an
      atraumatic vascular clamp for 6 h, then allowed to reperfuse. Animals receiving
      i.v. SLe(x) (25 mg/kg bolus + 50 mg/kg infusion over 10 h) 1) at the time of
      reperfusion, 2) 1 h after reperfusion, 3) 4 h after reperfusion, or 4) 12 h after
      reperfusion were compared with control animals receiving either saline or sialyl
      lactosamine, an oligosaccharide structurally similar to SLe(x) but not involved
      in selectin recognition. Tissue injury was assessed by serial measurement of ear
      edema and by visual determination of ear necrosis over 7 days. Tissue edema and
      necrosis were significantly reduced in animals treated with SLe(x) immediately
      upon reperfusion or after a 1-h delay, but not in animals for whom SLe(x)
      administration was delayed by 4 or 12 h. Furthermore, SLe(x) administration alone
      had no effect on circulating leukocyte or PMN counts, or PMN expression of CD18
      or L-selectin. We conclude that interruption of selectin-mediated adherence with
      soluble SLe(x) oligosaccharide attenuates reperfusion in the rabbit ear. The
      observation that SLe(x) is efficacious only if administered in the first hour
      after reperfusion suggests that the more immediately available P- and L-selectin
      participate in this PMN adhesion/injury process, whereas E-selectin, with its
      delayed endothelial expression, does not.

PMID- 7561111
TI  - The low affinity Fc gamma RIIa and Fc gamma RIIIb on polymorphonuclear
      neutrophils are differentially regulated by CD45 phosphatase.
AB  - Stimulation of human polymorphonuclear neutrophils through ligation and cross
      linking of the low affinity Fc gamma RIIa and Fc gamma RIIIb using mAb Fab and
      F(ab')2 fragments led to transient intracellular calcium mobilization and
      activation of the respiratory burst. Fc gamma RIIIb engagement resulted in a
      different pattern of intracellular calcium flux, and induction of the respiratory
      burst was significantly more effective than in the case of Fc gamma RIIa. These
      data demonstrate that the capacity of Fc gamma RIIIb to transduce transmembrane
      signals itself contributes to full cell activation. Treatment with a mAb F(ab')2
      fragment recognizing CD45 phosphatase suppressed Fc gamma R-induced calcium
      mobilization in a dose-dependent manner. An ongoing intracellular calcium
      mobilization was immediately terminated when activation was followed by co-cross
      linking Fc gamma R and CD45. This suggests that the initial steps of Fc gamma R
      signal transduction pathways are influenced by the state of tyrosine
      phosphorylation. Combined cross-linking of both receptors, however, was hardly
      susceptible to CD45. Also, inhibition of respiratory burst by CD45 in the case of
      Fc gamma RIIIb was minimal compared with that for Fc gamma RIIa. Signal
      transduction pathways of low affinity Fc gamma RIIa and Fc gamma RIIIb are
      differentially regulated by CD45, underlining the essential function of Fc gamma
      R-mediated tyrosine phosphorylation in polymorphonuclear neutrophil activation.

PMID- 7561112
TI  - Differential responsiveness of purified mouse c-kit+ mast cells and their
      progenitors to IL-3 and stem cell factor.
AB  - Murine mast cell development is regulated by a number of T cell- and fibroblast
      derived growth factors, of which IL-3 and stem cell factor (SCF) appear to be the
      most important. To determine the relative effects of these two growth factors on
      different stages of developing mast cells, we isolated highly purified
      populations of c-kit+ mast cells and their progenitors and examined their ability
      to respond to SCF and/or IL-3. We show that purified c-kit+ cells isolated from
      bone marrow, mesenteric lymph nodes of Nippostrongylus brasiliensis-infected
      mice, and the peritoneal cavity do not form mast cell colonies in response to SCF
      as a single agent. Although unpurified populations of lymph nodes of
      Nippostrongylus brasiliensis-infected mice or peritoneal cells were able to form
      mast cell colonies in response to SCF alone, this probably reflects paracrine
      factors produced by accessory cells. IL-3 alone did not promote mast cell colony
      formation from either population. Within bone marrow, we detected both
      multipotential and unipotential mast cell progenitors. Interestingly, IL-3 alone
      promoted only the development of multipotential progenitors, while SCF plus IL-3
      promoted both multipotential and unipotential mast cell progenitors. Together,
      these results indicate that the developmental/proliferative effects observed with
      a particular mast cell population is determined in part by the stage of
      maturation of mast cells at the time they are exposed to SCF and IL-3, and
      suggest that SCF primarily influences mast cell development only in the context
      of other cytokines.

PMID- 7561113
TI  - Isoforms of human C4b-binding protein. I. Molecular basis for the C4BP isoform
      pattern and its variations in human plasma.
AB  - Human C4b-binding protein (C4BP) is an important regulator of the complement
      system that also binds and inactivates the anticoagulant vitamin K-dependent
      protein S. These two activities are performed by two distinct polypeptides of 70
      kDa and 45 kDa known as alpha- and beta-chains, respectively. C4BP is present in
      plasma in various isoforms with different alpha beta composition. Here we report
      multiple discrete variations of the relative levels of the C4BP isoforms among
      normal individuals and provide evidence that they are determined by genetic
      factors that segregate with the regulator of complement activation gene cluster.
      We also report the characterization of the C4BP molecules secreted by HepG2 and
      Hep3B cells, as well as transfection experiments in COS cells, to illustrate that
      the relative levels of expression of the C4BPA and C4BPB genes play a major role
      in determining the proportion in which the different C4BP isoforms are
      synthesized. Altogether, the data indicate that the human C4BP isoform pattern is
      genetically determined, but can be modified by factors with a differential effect
      on the expression of the C4BPA and C4BPB genes. These observations provide a new
      way to explore the possible association between elevated levels of C4BP and an
      increased risk to thromboembolic disorders.

PMID- 7561115
TI  - Genetic analysis of experimental allergic encephalomyelitis in mice.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the
      central nervous system that exhibits many pathologic similarities with multiple
      sclerosis. While products of the MHC are known to control the development of EAE,
      it is clear that non-MHC products also influence susceptibility. The chromosomal
      locations of these were investigated in selective crosses between MHC class II
      compatible, EAE-susceptible Biozzi ABH, and low responder nonobese diabetic (NOD)
      mice. The disease was dominant and highly influenced by gender in the backcross
      one (BC1) generation. Female mice were significantly more susceptible than male
      mice. Segregation of disease frequency of female animals in this cross suggested
      that EAE was controlled by a major locus. Although microsatellite-based exclusion
      mapping indicated that a number of regions on chromosomes 5, 6, 7, 8, 9, 10, 11,
      12, 13, and 18 showed evidence of linkage (p < 0.05) compared with expected
      random distributions of alleles, disease susceptibility was most strongly linked
      (p < 0.001) to chromosome 7. However, by selectively analyzing animals that were
      either severely affected or almost normal, additional susceptibility loci were
      mapped on chromosomes 18 and 11 that were linked (p < 0.001) to resistance and
      the development of severe disease, respectively. The data indicate a major locus
      on chromosome 7, affecting initiation and severity of EAE that is probably
      modified by several other unlinked loci. These localizations may provide
      candidate loci for the analysis of human autoimmune-demyelinating disease.

PMID- 7561114
TI  - Isoforms of human C4b-binding protein. II. Differential modulation of the C4BPA
      and C4BPB genes by acute phase cytokines.
AB  - Human C4b-binding protein (C4BP) controls activation of the complement system and
      inactivates the anticoagulant vitamin K-dependent protein S using two distinct
      polypeptides known as C4BP alpha and C4BP beta, respectively. C4BP presents three
      isoforms, alpha 7 beta 1, alpha 7 beta 0, and alpha 6 beta 1, the proportion of
      which depends on the relative levels of C4BP alpha and C4BP beta. To better
      understand the regulation of C4BP during the acute phase response we analyzed the
      C4BP isoforms in 23 serial samples of acute phase patients and characterized the
      effect of various acute phase cytokines on the expression of the C4BPA and C4BPB
      genes using Hep3B cells. We show that the elevation of C4BP during acute phase
      response leads to changes in the proportion of the C4BP isoforms. However, there
      are striking differences among acute phase individuals. Some of them present a
      pattern of induction that primarily affects the alpha 7 beta 0 isoform, whereas
      others present the opposite situation, increasing the C4BP beta-containing
      isoforms. In vitro studies demonstrate that IL-6, IL-1 beta, and INF-gamma
      increase the levels of both C4BP alpha- and C4BP beta-mRNAs, whereas TNF-alpha
      down-regulates these mRNAs. INF-gamma shows, in addition, a differential effect
      on the C4BP alpha- and C4BP beta-mRNAs. Differential modulation of the C4BPA and
      C4BPB genes has been postulated as an efficient mechanism to maintain steady
      concentrations of C4BP beta when C4BP is induced. A synergistic 10-fold induction
      of C4BP alpha-mRNA, but a marginal increase of C4BP beta-mRNA, was observed when
      INF-gamma was used together with TNF-alpha, suggesting that association of these
      cytokines is critical to avoid elevation of C4BP beta during the acute phase
      induction of C4BP.

PMID- 7561116
TI  - Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis
      (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease.
AB  - Immunization of a limited number of rodent strains with central nervous system
      derived Ags induces experimental allergic encephalomyelitis (EAE). In contrast to
      susceptible female SJL mice, age-matched males are resistant to actively induced
      EAE. The ability of immunization with neuroAg to induce Ag-specific T cell
      activation in resistant male mice was examined. Ag-specific T cell proliferation
      was found following immunization of both male and female SJL mice. Draining lymph
      node cytokine mRNA patterns demonstrated that immunization of EAE-resistant male
      mice resulted in a Th2-type pattern. By contrast, immunization of EAE-susceptible
      female mice resulted in a Th1-type pattern. Priming of Th1- and Th2-type
      responses was confirmed by analysis of cytokines secreted following Ag-specific
      proliferation. In contrast to the transfer of myelin basic protein (MBP)-specific
      Th1-type T cells derived from female mice, which induced acute and relapse EAE,
      transfer of MBP-specific Th2-type T cells derived from male mice resulted in no
      clinical or histologic evidence of EAE. A mixture of MBP-specific Th1 and Th2
      type cells was transferred to naive recipients to determine if the neuroAg
      specific Th2-type cells exerted a regulatory influence on EAE. Acute disease was
      partially eliminated and relapses were completely eliminated in these recipients.
      Analysis of spinal cords showed the presence of both Th1 and Th2 cytokine mRNAs.
      These data are consistent with both the ability of Th2-type cells to suppress
      autoimmunity and a homeostatic mechanism of T cell regulation based on the cross
      regulation of Th1 and Th2 cells in the maintenance of peripheral tolerance.

PMID- 7561117
TI  - Cytokine patterns during progression to AIDS in children with perinatal HIV
      infection.
AB  - Patterns of cytokine expression were analyzed in polyclonal and antigenic
      responses in children with perinatal HIV infection. Responses of PBL to PMA and
      A23187 calcium ionophore studied in patients in different stages of HIV infection
      revealed reduced levels of IL-2 in HIV-infected children beginning before 6 mo of
      age, and age-dependent increases in expression of IL-4, IL-10, and IFN-gamma. The
      levels of IL-4, IL-10, and IFN-gamma expression did not differ significantly
      between HIV-infected and age-matched uninfected children of HIV-seropositive
      mothers, except for a small reduction in HIV-infected children in late stages of
      infection. Responses to PHA, HLA alloantigens, HIV envelope peptides T1 and P18,
      and tetanus toxoid were studied in PBMC derived from asymptomatic and mildly
      symptomatic HIV-infected children. IL-2, IFN-gamma, IL-4, and IL-5 expression was
      detected in PHA-stimulated PBMC from all analyzed patients. HIV-infected children
      who failed to respond to HLA alloantigens, tetanus toxoid, or the envelope
      peptides had lower numbers of CD4+ cells and expressed, on PHA stimulation,
      higher levels of IL-4 and IL-5 and lower levels of IL-2 and IFN-gamma than
      patients who responded to the antigenic stimulation. Results of these analyses
      suggest that cytokine expression in HIV-infected children depends on the
      character of the stimuli as well as the phenotype of PBMC, and indicate possible
      prevalence of Th2 Ag-specific responses during the progression of HIV-induced
      immunodeficiency.

PMID- 7561118
TI  - T lymphocytes from volunteers immunized with irradiated Plasmodium falciparum
      sporozoites recognize liver and blood stage malaria antigens.
AB  - The model of protective immunity induced by immunization with irradiated
      plasmodia sporozoites (SPZ) has become the prototype for a promising vaccine
      strategy based on Ab and CTL responses directed against pre-erythrocytic stage
      Ags, in particular the circumsporozoite protein (CSP) and sporozoite surface
      protein 2 (SSP2). However, results from recently conducted vaccine studies
      suggest that T cell responses directed against additional specificities might
      also be required for protection. We have tested this hypothesis by examining
      human T lymphocytes from irradiated Plasmodium falciparum SPZ-immune volunteers
      for proliferative reactivities to parasitized red blood cells (pRBC) and
      recombinant proteins and synthetic peptides representing certain liver and blood
      stage Ags. In this work, we report that although SPZ-induced protective immunity
      is stage-specific, SPZ-immune lymphocytes recognized determinants associated with
      erythrocytic and liver stage parasites. Thus, protective immunity induced by
      irradiated SPZ may depend upon responses against pre-erythrocytic Ags in addition
      to CSP and SSP2.

PMID- 7561119
TI  - Evidence for an antigen-specific cellular immune response in skin lesions of
      patients with psoriasis vulgaris.
AB  - Psoriasis vulgaris is an inflammatory skin disease characterized by excessively
      increased keratinocyte proliferation. Several lines of evidence support the idea
      that T cells infiltrating psoriatic skin lesions play a vital role in the
      pathogenesis of the disease. To establish whether lesional accumulation and
      activation of T lymphocytes reflect a specific local immune response, the TCR
      beta-chain variable (V beta) region gene usage was studied in chronic psoriatic
      plaques, normal skin, and paired blood lymphocytes. By semiquantitative PCR, we
      found that overexpression of either or both V beta 2 and V beta 6 gene families
      characterized the TCR repertoires of normal skin and psoriatic skin lesions.
      However, sequence analysis of the complementarity-determining region 3 (CDR3) of
      these V beta gene families demonstrated a marked TCR oligoclonality only in
      psoriatic lesions, not in normal skin or in blood lymphocytes. The amino acid
      sequences of the lesional TCR clones revealed that certain conserved junctional
      motifs were shared by different patients. A second biopsy taken from one of the
      psoriasis patients 18 mo later from a different anatomical site disclosed that
      the same TCR clones were again dominating. These data suggest that lesional
      psoriatic T lymphocytes expressing the prevailing TCR V beta genes represent an
      oligoclonal T cell subset that expanded from a few progenitor T cells in response
      to Ag in the skin of psoriasis patients. They are derived from a polyclonal T
      cell population that, by the expression of V beta 2 or V beta 6 TCR, appears to
      be predisposed for homing to the skin.

PMID- 7561120
TI  - Limited TCR repertoire of infiltrating T cells in the kidneys of Sjogren's
      syndrome patients with interstitial nephritis.
AB  - To analyze the mechanism of interstitial nephritis in patients with Sjorgren's
      syndrome (SS), we examined the TCR repertoire of infiltration T cells in kidney,
      labial salivary glands, and PBLs using a PCR. The repertoire of the TCR V beta
      gene on infiltrating T cells from the kidneys of SS patients was more restricted
      than those on infiltrating T cells in labial salivary glands and PBL. The TCR V
      beta 2 gene was expressed predominantly in six of seven (86%) SS patients.
      Junctional sequences of cDNAs encoding the V beta 2 gene on infiltrating T cells
      in the kidneys of five SS patients showed that some of the cells expanded
      clonally, indicating Ag-driven stimulation rather than superantigen-induced
      proliferation. The same V beta 2 clones in the kidney were not detected in labial
      salivary glands of the same SS patients; the conserved amino acid (arginine at
      position 96) in the CDR3 region of the V beta 2 gene was found at a frequency of
      48.0% in the kidney, whereas it was detected in only 15.4% of the clones in lips.
      In conclusion, these findings suggest the possibility that T cells that
      infiltrate the kidneys of SS patients with interstitial nephritis might recognize
      different autoantigens than those that infiltrate labial salivary glands.

PMID- 7561121
TI  - Paradoxical effects of IL-10 in endotoxin-induced uveitis.
AB  - Uveitis, or intraocular inflammation, can be provoked in laboratory rodents by
      the local or systemic injection of bacterial endotoxin. Many of the inflammatory
      effects of endotoxin are potentially due to the induction of cytokine synthesis.
      IL-10 is a cytokine that potently inhibits the synthesis of many cytokines,
      including IL-1 and TNF-alpha. We have assessed the ability of IL-10 to inhibit
      endotoxin-induced uveitis in rabbits and mice. The intravitreal injection of 1
      micrograms of human recombinant IL-10 was extremely effective in rabbits in
      reducing the inflammation produced by the intravitreal injection of 250 ng of
      Escherichia coli endotoxin, as judged by the reduced accumulation of cells and
      protein in the aqueous humor. Locally injected IL-10 was similarly effective in
      blocking the ocular inflammatory effects of intravitreally injected endotoxin in
      a mouse model. If the injection of IL-10 was delayed subsequent to the endotoxin
      injection, the reduced inflammatory effects in the rabbit model were diminished.
      In contrast to its ability to inhibit the local inflammatory effect of endotoxin
      in the eye, IL-10 did not reduce the inflammation induced by a local ocular
      injection of 400 U of human recombinant IL-alpha. Paradoxically, in a mouse model
      of uveitis subsequent to intraperitoneally injected endotoxin, the simultaneous
      injection of 1 micrograms of IL-10 and endotoxin potentiated the ocular
      inflammation, as judged by the number of leukocytes seen in histologic sections.
      This effect was dose dependent, since eye inflammation was markedly inhibited by
      100 micrograms of IL-10 injected i.p. These observations are compatible with the
      hypothesis that locally injected IL-10 acts by reducing cytokine synthesis in
      these uveitis models. Intraperitoneally injected IL-10 can either inhibit or
      suppress endotoxin-induced eye inflammation in a dose-dependent manner.

PMID- 7561122
TI  - Relationship between beta cell injury and antigen presentation in NOD mice.
AB  - We have made three observations that are important for our understanding of the
      dynamics of presentation of diabetogenic Ags in immunologically induced diabetes.
      First, the APC in the islets of Langerhans were found normally to contain
      diabetogenic peptides on their I-Ag7 molecules. This was found in freshly
      harvested islet cells from prediabetic NOD mice and, importantly, from NOD.SCID
      mice. Second, the presence of diabetogenic lymphocytes improved the presenting
      function of intra-islet APC. We interpret this to mean that lymphocytes can
      regulate intra-islet APC function before the development of diabetes. Finally,
      spleen APC can be found bearing diabetogenic Ag after acute injury to islets.
      These APC may be important in lymphocyte stimulation outside the environment of
      the pancreas.

PMID- 7561123
TI  - Lack of induction of antibodies specific for conserved, discontinuous epitopes of
      HIV-1 envelope glycoprotein by candidate AIDS vaccines.
AB  - We examined the humoral immune response in both HIV-1 infected and uninfected
      volunteers immunized with candidate HIV-1 recombinant envelope subunit vaccines
      (Genentech gp120IIIB, MicroGeneSys gp160IIIB, or ImmunoAG gp160IIIB).
      Immunization of both HIV-1 infected and uninfected volunteers with these
      immunogens resulted in the induction of Abs preferentially reactive with epitopes
      accessible on a denatured form of gp120. While sera from HIV-1 uninfected
      gp120/gp160IIIB vaccinees bound gp120/gp41, which was expressed on the surface of
      H9 cells infected with HIV-1IIIB, minimal binding to HIV-1MN or HIV-1RF infected
      cells was obtained. Induction of qualitatively similar immune responses by these
      immunogens would not have been predicted based on their different tertiary
      structures. These data indicate a restriction of the immune response to linear,
      conserved epitopes poorly accessible on both monomeric gp120 and cell-surface
      expressed oligomeric gp120/gp41 and a lack of Abs specific for conformational
      epitopes conserved across divergent HIV-1 strains. Poor recognition of HIV-1
      envelope tertiary and quaternary structure may explain the restricted
      neutralization profiles of vaccinee sera against laboratory-adapted strains of
      HIV-1 and their inability to neutralize primary HIV-1 isolates. Alternate
      immunogens or reformulations with the capacity to elicit Abs that preferentially
      bind to natively folded gp120 should be investigated and correlated with their
      ability to neutralize more diverse laboratory-adapted and primary HIV-1 isolates.

PMID- 7561124
TI  - Both a precursor and a mature population of dendritic cells can bind HIV.
      However, only the mature population that expresses CD80 can pass infection to
      unstimulated CD4+ T cells.
AB  - Dendritic cells (DC) are the principle APC involved in primary immune responses;
      their major function is to obtain Ag in tissues, migrate to lymphoid organs, and
      activate T cells. DC are also the first immune cells to arrive at sites of
      inflammation on mucous membranes, the major site of sexual transmission of HIV.
      We have demonstrated previously that three populations of cells that can develop
      a dendritic morphology are present in peripheral blood. Two of these populations
      can express CD83, a marker of DC, and appear to be at different stages of
      maturation: 1) a precursor population and 2) a mature immunostimulatory DC.
      Precursor-derived DC express high levels of CD86 (B7-2) and HLA-DR but no CD80
      (B7-1), whereas mature DC have high levels of expression of all three markers.
      Mature DC in peripheral blood bind HIV to their surface and induce infection when
      added to autologous CD4+ T cells in the absence of added stimuli, such as
      mitogens. These mature DC, when isolated directly from peripheral blood, appear
      to be conjugated to T cells, and these conjugates are infected easily and
      productively with HIV. These findings suggest a role for DC in early HIV
      infection in which they bind virus and interact with T cells locally or after
      migrating to a lymphoid organ, thus establishing a productive infection.
      Furthermore, they likely play a role in the propagation of HIV infection by
      activating T cells in the presence of HIV, which leads to viral replication and
      immune cell destruction.

PMID- 7561125
TI  - High avidity state of leukocyte function-associated antigen-1 on rheumatoid
      synovial fluid T lymphocytes.
AB  - The integrin LFA-1 (CD11a/CD18) is a cell surface adhesion molecule required for
      leukocyte extravasation and subsequent immune and inflammatory responses. Rapid
      transition between nonadherent and adherent states of LFA-1 is of key importance
      to Ag-specific recognition of T lymphocytes. In this paper, LFA-1-mediated
      adhesiveness of peripheral blood (PB) and synovial fluid (SF) T lymphocytes to
      affinity-purified ICAM-1-coated plates was studied in patients with rheumatoid
      arthritis (RA) and in patients with non-RA panels, including osteoarthritis,
      ankylosing spondylitis, erythema nodosum, pseudogout, and pustulosis. LFA-1
      mediated adhesiveness of SF T lymphocytes was not observed in any of the 10 non
      RA patients studied, although cross-linking of the TCR on lymphocytes from these
      patients rapidly converted LFA-1 to an adhesive state. In contrast, SF T
      lymphocytes from 10 of 12 RA patients exhibited LFA-1-mediated adhesiveness
      without a requirement for cross-linking of the TCR. No difference was seen in the
      cell surface density of LFA-1 between non-RA and RA T lymphocytes, suggesting
      that the difference in adhesiveness was due to a high avidity state of LFA-1 on
      SF T lymphocytes in RA. Furthermore, exposure of PB T lymphocytes, which showed a
      low avidity state of LFA-1, to whole SF from RA patients that was depleted of T
      lymphocytes could induce a high avidity state of LFA-1 in vitro. Cellfree SF from
      RA patients also could stimulate adhesiveness, although to a lesser extent. These
      data suggest the existence of a LFA-1-activating environment that is selectively
      found in SF from RA patients.

PMID- 7561126
TI  - Detection of human cytokines in situ using antibody and probe based methods.

PMID- 7561127
TI  - Acid hydrolysis of monoclonal antibodies.
AB  - For analysis of monoclonal antibodies using polyacrylamide gel electrophoresis,
      two hydrolytic fragments derived from the heavy chain of mouse IgG1 were produced
      during incubation of the antibodies in Laemmli reducing sample buffer at 100
      degrees C for 5 min. The cleavage sites were identified by amino terminal
      sequencing. Results indicate that the final pH of the mixture is critical for the
      production of the fragments which are generated when the pH is approximately 6.0.
      At pH 8.0, no fragments are detected. The relevance of this finding to those
      working with monoclonal antibodies is discussed.

PMID- 7561128
TI  - Prediction of binding to MHC class I molecules.
AB  - The binding of antigenic peptide sequences to major histocompatibility complex
      (MHC) molecules is a prerequisite for stimulation of cytotoxic T cell responses.
      Neural networks are here used to predict the binding capacity of polypeptides to
      MHC class I molecules encoded by the gene HLA-A*0201. Given a large database of
      552 nonamers and 486 decamers and their known binding capacities, the neural
      networks achieve a predictive hit rate of 0.78 for classifying peptides which
      might induce an immune response (good or intermediate binders) vs. those which
      cannot (weak or non-binders). The neural nets also depict specific motifs for
      different binding capacities. This approach is in principle applicable to all MHC
      class I and II molecules, given a suitable set of known binding capacities. The
      trained networks can then be used to perform a systematic search through all
      pathogen or tumor antigen protein sequences for potential cytotoxic T lymphocyte
      epitopes.

PMID- 7561129
TI  - Differential recognition of free and covalently bound polyamines by the
      monoclonal anti-spermine antibody SPM8-2.
AB  - The reactivity of an anti-spermine MAb (SPM8-2) toward polyamines either free or
      bound to a solid surface was investigated using equilibrium dialysis and ELISA
      methods. When polyamines were covalently linked to hydrophilized microtiter
      plates using carbodiimide, the MAb SPM8-2 reacted both with spermine and
      spermidine, with a higher affinity for the latter, but did not show any
      reactivity towards bound putrescine. In contrast, the MAb SPM8-2 reacted with all
      three polyamines bound to the microtiter plates with glutaraldehyde, with an
      affinity in the order: putrescine > spermidine > spermine. Equilibrium dialysis
      and competitive ELISA tests showed that the MAb SPM8-2 exhibited high affinity
      for free spermine and 50% and 5% cross-reactivity with free spermidine and
      putrescine respectively. The affinity of the MAb SPM8-2 for putrescine,
      spermidine and spermine appears to depend on whether the polyamine is free or
      bound. The antigenicity of the polyamines differs according to the nature of
      their link to the solid phase. These observations are discussed in the light of
      the structural modification produced by covalent binding of the polyamines. It is
      also concluded that when antibodies are used, due care has to be exercised in
      choosing the appropriate immunoassay for determining the specificity of
      antibodies directed against small haptens such as the polyamines.

PMID- 7561131
TI  - A versatile flow cytometry-based assay for the determination of short- and long
      term natural killer cell activity.
AB  - A flow cytometry based method has been developed to assess natural killer (NK)
      cell activity in both short-term (4 h) and long-term (18 h) NK assays. Target
      cells were either labeled with PKH-2, c'FDA or D275. Simultaneously, dead cells
      were identified by counter-staining with the nuclear dye propidium iodide. Using
      flow cytometry, only D275 in combination with propidium iodide permits the
      differentiation of four cell populations: live target cells, dead target cells,
      live effector cells, and dead effector cells. Even after the extended incubation
      periods (18 h) necessary for the determination of NK activity in some domestic
      animals these four populations remain clearly distinguishable. Comparison of
      results with cells of normal human individuals obtained using this D275/propidium
      iodide flow cytometry assay with data derived from fluorescence microscopy or an
      endogenous lactate dehydrogenase release assay shows a strong correlation. Since
      in long-term NK assays a high proportion of dead effector cells is constantly
      observed this cell population frequently limits the use of the lactate
      dehydrogenase release assay but does not interfere with the flow cytometry assay
      presented here. Using this novel assay, we have demonstrated the suppressive
      effects of defined glycosaminoglycans on long-term porcine NK activity.

PMID- 7561130
TI  - A simple, rapid and sensitive fluorimetric assay for the measurement of cell
      mediated cytotoxicity.
AB  - A fluorimetric method using 4-methylumbelliferyl heptanoate (MUH) has been
      developed for detecting cell-mediated cytotoxicity and cell proliferation. The
      assay is based on the hydrolysis of the fluorochrome (MUH) by intracellular
      esterases of viable cells resulting in the production of highly fluorescent 4
      methylumbelliferone that can be measured in a microplate fluorimeter. Because of
      a similarity to the principle of the widely used colorimetric MTT assay, a
      comparison was made between the two assays when measuring cell proliferation and
      LAK cell cytotoxicity to different target cell types. The results have shown that
      the MUH assay represents a method for evaluating both cell-mediated cytotoxicity
      and cell proliferation which is completely comparable to the MTT method. The
      rapidity of the new cytotoxicity assay, 5 h in contrast to 9 h for the MTT assay,
      its applicability to both adherently and nonadherently growing target cells and
      its high accuracy due to the avoidance of centrifugation steps make this method a
      serious contender for replacing conventional radioactive techniques.

PMID- 7561132
TI  - Specific detection of the precursor of ras p21 with a mouse monoclonal anti-C
      terminal peptide antibody, SARA-K1.
AB  - In an attempt to clarify the post-translational modifications of ras oncogene
      product p21, we have established a mouse monoclonal antibody specific for the
      precursor of p21. The C-terminal peptide (156-188) of K(4A)-ras oncogene product
      p21 (p21K(4A), termed K(4A)-peptide, was used as the immunogen. In Western
      blotting, monoclonal antibodies were examined for their differential reactivity
      between two types of p21K(4A) expressed in Escherichia coli (esh-p21K(4A)) and
      mammalian cell (mam-p21K(4A)). One monoclonal antibody, designated SARA-K1,
      reacted selectively with esh-p21K(4A). The epitope for SARA-K1 was defined on
      tryptic peptide (177-184), containing Cys180, of the K(4A)-peptide. Pulse-chase
      experiments of mam-p21K(4A) synthesis at 24 degrees C revealed that SARA-K1
      precipitated a 21 kDa protein within a 7 min chase but not after a 10 min chase,
      indicating that SARA-K1 recognizes the precursor of mam-p21K(4A). Furthermore, in
      Triton X-114 partitioning experiments using mammalian cells pre-treated with
      Mevalotin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor,
      SARA-K1 precipitated [35S]methionine-labeled, [3H]mevalonic acid-unlabeled mam
      p21K(4A) in the aqueous phase, but did not precipitate [3H]mevalonic acid-labeled
      mam-p21K(4A) in either aqueous or detergent phase. The data presented clearly
      show that the SARA-K1 specifically recognizes the primary translational product
      pro-p21K(4A).

PMID- 7561133
TI  - Detection of Haemophilus ducreyi lipooligosaccharide by means of an immunolimulus
      assay.
AB  - A murine monoclonal antibody (MAb) directed against a surface-exposed epitope of
      the lipooligosaccharide (LOS) of Haemophilus ducreyi strain 35000 was shown to be
      reactive with all 37 strains of this pathogen tested in a colony blot
      radioimmunoassay. The LOS epitope bound by this MAb appeared to be stably
      expressed by H. ducreyi growing in vitro. The use of this MAb in the
      immunolimulus system revealed that it could detect purified H. ducreyi LOS at a
      level of 25 pg/ml. Similarly, this immunolimulus system could detect as few as
      1000 colony forming units of in vitro-grown H. ducreyi cells per ml of buffer.
      When this MAb was utilized in the immunolimulus system together with lesion
      material from rabbits infected with two different H. ducreyi strains, a positive
      reaction was obtained with every sample tested, even when no viable organisms
      were present in the lesion material. In contrast, this MAb yielded consistently
      negative results when used in the immunolimulus system with lesion material from
      animals infected with Staphylococcus aureus.

PMID- 7561134
TI  - Versatile E. coli thioredoxin specific monoclonal antibodies afford convenient
      analysis and purification of prokaryote expressed soluble fusion protein.
AB  - A recently developed E. coli thioredoxin (Trx) gene fusion expression system has
      circumvented the difficulties associated with inclusion body formation. Although
      ample quantities of soluble recombinant protein can be expressed using this
      system, no universal means of quantifying or purifying the fusion product exists.
      To facilitate the study of Trx fusion proteins, anti-E. coli Trx monoclonal
      antibodies (mAb) were generated. Two distinct Trx epitopes were defined by
      competitive ELISA. Both mAb were capable of detecting Trx fusion proteins by
      sandwich ELISA, and by immunoblot analysis under reducing and non-reducing
      conditions. In addition, these mAb enabled purification of Trx fusion proteins by
      immunoprecipitation, as well as affinity chromatography. This report provides the
      first description of anti-Trx antibodies. These reagents represent a major
      advance in the isolation and analysis of prokaryote expressed recombinant Trx
      fusion proteins.

PMID- 7561135
TI  - Quick purification of recombinant human truncated tau proteins for
      immunoanalysis.
AB  - A simple and rapid purification method is described which exploits the heat
      stability of human tau (tau) protein to prepare truncated forms of this protein
      derived from bacteria. Bacterial cells expressing tau fragments were pelleted,
      resuspended in phosphate buffered saline and boiled for 5 min. After
      centrifugation the supernatant containing thermostable tau was filtered (0.45
      microns) and used for immunoanalysis with monoclonal antibodies. The purified tau
      fragments exhibited identical antigenic properties as fragments isolated by a
      conventional procedure, based on ion exchange chromatography on phosphocellulose.
      In contrast to the conventional approach, our method is less complicated, cheaper
      and significantly reduces the time required for isolation of the recombinant tau
      fragments.

PMID- 7561137
TI  - Detection of brain-reactive autoantibodies in the sera of patients with systemic
      lupus erythematosus and cerebral involvement.
AB  - We modified, and applied to man, an ELISA established for the detection of brain
      reactive autoantibodies in a murine model of SLE. We found brain-reactive
      antibody levels to be significantly higher in lupus patients than in healthy
      subjects. The antibody levels were significantly higher in lupus patients with
      central nervous system involvement than in those without.

PMID- 7561136
TI  - YOPRO-1 permits cytofluorometric analysis of programmed cell death (apoptosis)
      without interfering with cell viability.
AB  - In the absence of cell permeabilization, the impermeant nuclear dye YOPRO-1
      permits accurate analysis of apoptosis using cytofluorometry or fluorescent
      microscopy. Several immune cell populations were studied including dexamethasone
      treated thymocytes, irradiated peripheral blood mononuclear cells and a growth
      factor-depleted tumor B cell line. Excellent correlation values were found with
      acridine orange using cytofluorometry and with eosin-hematoxylin using optical
      microscopy. Under fluorescent microscopy, YOPRO-1-fluorescent cells demonstrate
      the morphological features of cells undergoing apoptosis such as nuclear
      shrinkage and fragmentation. An important characteristic of the dye that differs
      from all other nuclear dyes previously used for the detection of apoptosis is
      that it does not label living cells. Cell sorting after flow cytofluorometry
      analysis confirmed that only the apoptotic cell population was labelled with
      YOPRO-1. Further studies showed that while incubation of living cells with
      Hoechst 33342 almost completely abrogated the capacity of T cells to proliferate
      in response to several stimuli, YOPRO-1 had no inhibitory effect. This new
      simple, rapid and reproducible use of the YOPRO-1 dye should prove useful in the
      analysis of apoptotic cells as well as for investigations of the functional
      properties of living cells in a culture containing apoptotic cells.

PMID- 7561138
TI  - Antibodies to lipopolysaccharide.
AB  - Lipopolysaccharides (LPS) are indispensable structural components of the Gram
      negative bacterial outer membrane and are major determinants of virulence in
      pathogenic species. In the infected host LPS is better known as endotoxin where
      it acts as a potent stimulator of the inflammatory response. This article reviews
      the methods for the production and measurement of anti-LPS antibodies, and then
      describes the uses to which these methods have been employed. Antibodies to LPS
      (either monoclonal or polyclonal) may be used directly as immunotherapeutic
      agents for the treatment of Gram-negative sepsis or endotoxaemia, or as probes
      for the diagnosis and epidemiological investigation of Gram-negative bacterial
      infections. Antibodies are useful tools for investigation of the chemical
      structure of LPS, its expression on bacteria and to study the role of LPS in
      pathogenic mechanisms. The detection and quantitation of anti-LPS antibodies has
      formed the basis of classical and more recent serological studies of major
      bacterial infections.

PMID- 7561139
TI  - The use of non-radioactive chromium as an alternative to 51Cr in NK assay.
AB  - A novel method to measure target cell cytolysis based on the use of 'cold', non
      radioactive chromium and on the determination of metal release by graphite
      furnace atomic absorption spectroscopy (FAAS) is proposed. Natural killer (NK)
      assays were performed by labelling target cells with chromium as Na2CrO4, and
      results were compared with those obtained by conventional overnight labelling
      with 51Cr of targets killed by the same effectors. The cytotoxic capacity of
      peripheral blood lymphocytes from healthy subjects was evaluated, and NK activity
      measured with both methods showed a good agreement at each of the tested effector
      to target cell ratios (between 100:1 and 1:1), with a high and significant
      coefficient of correlation (r = 0.931, p < 0.0001). The selection of the
      appropriate Cr concentrations for labelling target cells took into account both
      the sensitivity of our instrumentation and the possible toxic effects of the
      metal. A study of the effects of Cr on the cell line (K562) which is usually
      employed as a target in NK tests showed that Cr could have a detrimental effect
      on cellular function, with significant numbers of cells with depolarised
      mitochondria and reduced DNA synthesis after 24 h incubation using Cr levels
      higher than 15 mumol/l (780 micrograms/l). The method proposed here has a number
      of advantages, including the use of a non-radioactive tracer, limited costs, high
      sensitivity and reproducibility, and the possibility of storing samples. In
      addition, the technique uses a fixed Cr concentration which is known to be non
      toxic.

PMID- 7561140
TI  - Scanning tunnelling microscopy and dynamic contact angle studies of the effects
      of partial denaturation on immunoassay solid phase antibody.
AB  - A range of partial denaturation antibody pre-treatments that affect immunoassay
      performance have been evaluated. Monoclonal anti-ferritin antibody was either
      partially denatured by heat, urea or pH pre-treatment or left untreated and then
      passively adsorbed to polystyrene microtiter wells. The adsorption
      characteristics and functionality of the different surfaces produced have been
      evaluated by dynamic contact angle (DCA) analysis and scanning tunnelling
      microscopy (STM) imaging respectively. The DCA data show that the effect of
      partial denaturation is to change the wetting characteristics of the antibody
      surfaces, while, in addition, STM imaging reveals marked effects seen in the
      aggregation properties of the denatured antibodies.

PMID- 7561143
TI  - Variability in the growth sustaining capacity of medium batches.
AB  - Medium batches, analysed in various spontaneous and mitogen induced proliferation
      assays, revealed heterogeneity in their growth promoting activity. This can
      critically affect test results and suggests that culture media can be a source of
      variability and problems in cell culture work. The manufacturers of media should
      broaden their quality control of medium batches.

PMID- 7561142
TI  - Establishment of an enzyme-linked immunosorbent assay (ELISA) for measuring
      cellular MAGE-4 protein on human cancers.
AB  - The MAGE genes encoding tumor-rejection antigens are expressed on various human
      cancers. An enzyme-linked immunosorbent assay (ELISA) was established for
      measuring cellular MAGE-4 protein (MAGE-4a and/or -4b) expressed on human tumor
      cells using a monoclonal antibody (mAb) and polyclonal Ab to recombinant MAGE-4b
      protein. Both the R5 mAb (IgG1) and the polyclonal Ab recognized a 45 kDa protein
      in extracts of MAGE-4 mRNA positive cancers, and showed no apparent cross
      reactivity to the other MAGE gene products (MAGE-1, -2, -3, -6, and -12) by the
      immunoblot analyses. The R5 mAb and the polyclonal Ab primarily recognized one
      (the position 119-133) and two oligopeptides (the positions 119-133 and 259-273),
      respectively, among a series of 31 different MAGE-4b oligopeptides. The amino
      acid sequences of these two peptides were identical to those of MAGE-4a and -4b,
      but differed from those of all the other MAGE proteins (MAGE-1, -2, -3, -6, and 
      12). Substitution of glycine for amino acid in position 123 (arginine, R), 124
      (lysine, K), 126 (R) or 128 (K) in a MAGE-4b oligopeptide of the position 119-132
      severely decreased the reactivity of the R5 mAb to the oligopeptide. This ELISA
      also showed no apparent cross-reactivity with the other MAGE gene products (MAGE
      1, -2, -3, -6, and -12). The minimum detectable level of MAGE-4 protein was
      determined to be 10 pg/well (100 pg/ml). The results suggest that this ELISA is a
      reliable and quantitative method to measure cellular MAGE-4 protein that is a
      potential target molecule for specific immunotherapy of human cancers.

PMID- 7561141
TI  - Selection of specific phage-display antibodies using libraries derived from
      chicken immunoglobulin genes.
AB  - In chickens, single functional immunoglobulin variable and joining gene segments
      at each of the heavy and light chain loci undergo V(D)J rearrangement. Diversity
      is subsequently introduced by conversions templated by upstream pseudo V region
      genes in such a way that practically all V regions in mature B cells have
      identical ends. This greatly simplifies the representative amplification of V
      region genes. Furthermore, the entire naive repertoire of the adult chicken is
      produced in the bursa of Fabricius of the young bird. These special properties of
      the generation of immunoglobulin diversity in chickens have been exploited in the
      development of procedures to produce large libraries of diverse antibody
      combining sites derived from chicken Ig genes and expressed on filamentous
      bacteriophage. The utility of this library was assessed by selection of
      specifically binding phage using three solid phase-bound protein antigens, hen
      egg white lysozyme, bovine thyroglobulin and bovine serum albumin. The sequences
      of the V region genes thus isolated demonstrated that selection was specific and
      that the library contained useful diversity of binding sites. This library
      provides access to a repertoire whose diversity is based on a mechanism different
      from that underlying previously available libraries. The demonstrated feasibility
      of generating chicken phage antibodies may lead to the production of monoclonal
      reagents from immunised chickens, and the derivation of reagents for studying
      immunoglobulin mediated selection in avian B cell development.

PMID- 7561144
TI  - Long-term production of human monoclonal antibodies by human-mouse
      heterohybridomas.
AB  - Production of monoclonal antibodies (mAbs) by fused somatic cells was first
      developed by Kohler and Milstein two decades ago, but its utilization for the
      production of human mAbs, particularly those bearing kappa chains, has been
      difficult because heterohybridomas formed with mouse myeloma cells are unstable
      and tend to lose certain of their human chromosomes. We have stabilized two such
      heterohybridomas over one year period and induced the production of kappa-bearing
      and lambda-bearing human mAb, respectively. Increased productivity was achieved
      by adding the Na+K(+)-ATPase inhibitor, ouabain and a cell mitosis inhibitor,
      cytochalasin B, to the cell culture media.

PMID- 7561145
TI  - Preparation of soluble recombinant T cell receptor alpha chain by using a
      calmodulin fusion expression system.
AB  - We have isolated a full length T cell receptor alpha chain (TCR alpha) cDNA
      derived from a bee venom phospholipase A2-specific mouse suppressor T cell
      hybridoma. A bacterial fusion expression system was constructed using rat
      calmodulin as a fusion partner for production of soluble TCR alpha. In this
      system, calmodulin-TCR alpha fusion protein was expressed at a high level in the
      soluble fraction of bacterial cell lysate, and could be purified by binding of
      calmodulin portion of the protein to phenyl-Sepharose. Using this system, fusion
      proteins containing a TCR alpha peptide corresponding to the complete
      extracellular region, V alpha-J alpha region or C alpha extracellular region were
      isolated. TCR alpha peptides were then released from the fusion proteins by
      digestion with thrombin which recognizes a linker sequence between calmodulin
      portion and TCR alpha segment. Polyclonal antibodies against constant region of
      TCR alpha chain (C alpha) were obtained by immunization of rabbits with the
      recombinant C alpha peptide. ELISA for TCR protein was established by using the
      polyclonal antibodies and the monoclonal antibody specific for C alpha region.

PMID- 7561146
TI  - Cytokine-based human whole blood assay for the detection of antigen-reactive T
      cells.
AB  - The measurement of cytokines produced by activated T cells refines assessment of
      cellular immune function and facilitates whole blood T cell assays. The latter
      approximate conditions in vivo and obviate the need to purify blood mononuclear
      cells. We have investigated the parameters of the whole blood assay in humans to
      standardize and optimize the detection of tetanus-specific T cell cytokine
      responses. Optimal conditions include the use of undiluted whole blood, an
      incubation time of 36-48 h and a minimum of delay between venesection and
      incubation of the blood with antigen. Blood should be drawn at a standard time of
      day to minimize inter-assay variation due to diurnal rhythmicity in cytokine
      production. Interferon-gamma or interleukin-2 are specific and reliable readouts;
      other cytokines can be measured to further characterize the TH1 and TH2 elements
      of the T cell responses, although tetanus-stimulated IL-4 production is detected
      in only a minority of healthy individuals. The whole blood assay is a potentially
      valuable tool for assessing cellular immune function and screening for antigen
      reactive T cells in humans.

PMID- 7561147
TI  - Determination of humanized anti-Tac in human serum by a sandwich enzyme linked
      immunosorbent assay.
AB  - A 'sandwich' enzyme-linked immunosorbent assay has been developed for measuring
      humanized anti-Tac (HAT), a humanized antibody to the IL-2 receptor on activated
      T cells (Tac), in human serum. The working range of this assay is 25-400 ng/ml
      with an overall precision of 5%. In this assay, the analyte, HAT, is sandwiched
      between Tac which is bound to a microtiter plate and biotinylated Tac that is
      conjugated to peroxidase labelled streptavidin. This assay was utilized to
      determine the pharmacokinetic parameters of HAT in patients with graft-versus
      host disease.

PMID- 7561148
TI  - A novel ELISA for the assessment of classical pathway of complement activation in
      vivo by measurement of C4-C3 complexes.
AB  - Measurements of complement split products by enzyme-linked immunosorbent assays
      (ELISA) are well established for the assessment of in vivo complement activation.
      We have combined two monoclonal antibodies (mAb) with specificities for
      C3b/iC3b/C3dg (mAb I3/15) and C4/C4b/C4d (mAb M4d2), respectively, in a sandwich
      ELISA to quantitate C4-C3 complexes as an indicator of complement activation.
      Serum incubated with heat aggregated IgG (HAG) was used as a standard and the C4
      C3 levels expressed as microgram equivalent HAG/ml (microgram HAG-equ/ml). Normal
      values of C4-C3 complexes in plasma (EDTA) of healthy probands (n = 11) were 6.3
      micrograms HAG-equ/ml +/- 1.5 (mean +/- 1 standard deviation (SD), with a range
      from 3.6 to 9.1). In patients with systemic lupus erythematosus (SLE, n = 23) C4
      C3 values were clearly elevated (48.8 micrograms HAG-equ/ml +/- 52.9, range 7.5
      184.7) as compared to samples from patients with idiopathic hypertension (IDH, n
      = 10) (6.5 micrograms HAG-equ/ml +/- 1.7, range 4.1-9.4). For SLE patients C4-C3
      levels significantly correlated with values for C3b/iC3b/C3d (r = 0.69, p <
      0.001) and C3 containing immune complexes (r = 0.68, p < 0.001), but not with the
      C4d fragment (r = 0.26). C4-C3 levels of 96% of the studied SLE patients were
      increased more than 2 SD above the normal mean as compared to 74% of C4d and
      activated C3 values, respectively. Serum treated with zymosan as an activator of
      the alternative pathway of complement did not exhibit higher C4-C3 values. These
      results demonstrate that the quantitation of in vivo generated C4-C3 complexes by
      ELISA provide a novel, sensitive parameter for classical pathway of complement
      activation.

PMID- 7561149
TI  - Fetal calf serum in growth medium obscures the detection of early anticardiolipin
      antibody secreting clones.
AB  - We have examined the effect of fetal calf serum (FCS) on the detection of early
      anticardiolipin antibody (ACL) secreting clones, using two well-established human
      IgG clones, LJ1 and AH2. By plating cells at 50/well and growing both clones
      simultaneously in standard growth (SG) medium containing 10% FCS, and in serum
      free (SF) medium, we were able to measure by ELISA the total IgG and ACL levels
      in the supernatants. The mean OD values (x 1000) against cardiolipin for both LJ1
      and AH2 were significantly higher for clones grown in SF than in SG medium: 331
      OD units vs. 172, and 275 OD units vs. 166 respectively (p < 0.001). Importantly,
      the number of wells in which the OD value was > 0.25 units above background was:
      for LJ1 in SG only 3/36 vs. 30/36 in SF; similarly, for AH2 1/36 in SG vs. 22/36
      in SF. In comparison, the total IgG assay using an OD value > 0.7 units above
      background, detected immunoglobulin secretion in all but one of the wells. We
      conclude that in ELISA procedures FCS in SG medium competes with solid phase
      cardiolipin for antibody binding. We suggest that these antibodies are binding to
      phospholipid from microvesicles found in FCS. We recommend that minimally
      'positive' clones on testing should be re-tested and, if necessary, switched to
      SF medium in order to prevent such clones from being discarded prematurely.

PMID- 7561150
TI  - Phosphatidylinositol hydrolysis in freshly isolated human T lymphocytes.
AB  - Antigen receptor-mediated activation of T and B lymphocytes results in activation
      of phospholipase C-gamma isozymes with subsequent hydrolysis of membrane inositol
      phospholipids. As a method of screening autoimmune or immunodeficient patients
      for early receptor signaling defects, we have developed a rapid technique for
      studying phosphatidylinositol (PI) hydrolysis in cultured cells and fresh
      clinical specimens resulting from surface receptor crosslinking. Using
      staphylococcal alpha-toxin, we permeabilized freshly isolated, purified human T
      lymphocytes to facilitate incorporation of [3H]myoinositol into membrane
      phospholipids. Aggregation of surface antigen receptors (TCR-CD3 complex and CD28
      on T cells) with specific antibodies produced extensive ATP and Mg(2+)-dependent
      hydrolysis of the membrane inositol phospholipids as measured by release of water
      soluble inositol phosphates. Anti-human CD3 antibody produced 18.5 +/- 1.6 net %
      PI hydrolysis and anti-human CD28 antibody produced 4.6 +/- 0.2 net % PI
      hydrolysis. Simultaneous anti CD3/CD28 crosslinking produced 30.8 +/- 1.2 net %
      PI hydrolysis, an increase over either stimulus alone (p = 0.0013 two tailed t
      test). Isotype matched control antibodies produced 11.6 +/- 0.4% PI hydrolysis.
      The tyrosine phosphatase inhibitor orthovanadate (Na3VO4) was used as a positive
      control because it induces maximal protein tyrosine kinase-dependent PI
      hydrolysis in permeabilized cells. Na3VO4 consistently induced hydrolysis of >
      50% of the membrane inositol phospholipid pool. These data indicate that
      costimulation of T cells with antibodies to CD3 and CD28 is synergistic and
      reinforces the importance of CD28 as an accessory T cell stimulus. This easy
      technique allows quick evaluation of the integrity of the early signaling cascade
      in lymphocytes as a screen for autoimmune and immunodeficiency diseases.

PMID- 7561151
TI  - Multiple estimation of concentrations in immunoassay using logistic models.
AB  - Immunoassay techniques yield estimates of concentrations of analytes based on
      comparison to known concentrations of a reference solution. The use of the
      nonlinear logistic model makes the error estimates and confidence levels
      approximate. When the goal of such a study is estimation of several unknowns,
      methods in common usage do not account for 'simultaneous' inference, i.e. the
      repeated use of the standard curve for estimating several concentrations.
      Alternative methods are described which take multiple use of the reference curve
      into account. Simulations using normally distributed data with variance
      proportional to a power of the mean compare different methods of obtaining
      calibration intervals and illustrate the approximate nature of all such
      techniques. Calibration intervals based on simple, commonly used methods do not
      provide the coverage promised, even for one-at-a-time estimation, and are not
      suited for multiple estimation and comparison.

PMID- 7561152
TI  - Radioimmunoassays for glutamic acid decarboxylase (GAD65) and GAD65
      autoantibodies using 35S or 3H recombinant human ligands.
AB  - Autoantibodies are an important marker of human autoimmune diseases and the
      development of simple, precise and reproducible immunoassays to detect
      autoantibodies is important to our understanding of human autoimmunity. GAD65
      autoantibodies occur frequently in insulin-dependent diabetic patients and is a
      useful marker for IDDM. A RIA to detect immunoreactive GAD65 has not been
      described. In the present study we describe a semi-automated fluid-phase
      immunoassay for the rapid detection of GAD65 autoantibodies in human serum. We
      also developed a sensitive RIA to determine immunoreactive human GAD65 in
      biological fluids and in vitro cell systems. Using in vitro translated
      recombinant human GAD65 in a multiwell-adapted procedure, our GAD65Ab RIA
      combines high specificity and sensitivity with a high capacity to analyze a large
      number of samples. In this report the three critical steps in the GAD65Ab RIA,
      DNA preparation, in vitro translation and immunoprecipitation, have been
      optimized. In our RIA, GAD65Ab were detected in 116/155 (75%) new onset Swedish
      IDDM children and in 1/85 (1.2%) healthy controls. In an immunoassay to detect
      autoantibodies against the proinsulin converting enzyme 2 (PC-2) no such
      antibodies were detected in IDDM patients. In the GAD65 RIA the lower detection
      limit was 2 ng/ml (31 fmol/ml). Our data demonstrate that autoantigen
      radioligands produced by in vitro translation are useful in RIA for
      autoantibodies and autoantigens in studies of human autoimmunity.

PMID- 7561153
TI  - Mutations in epidermolysis bullosa simplex.

PMID- 7561154
TI  - Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin
      and increases the threshold to provocation of polymorphic light eruption.
AB  - The sunburn response is markedly reduced by dietary fish oil rich in omega-3
      polyunsaturated fatty acids. Because prostaglandins mediate the vasodilatation,
      we examined the effect of fish oil on ultraviolet (UV) B-induced prostaglandin
      metabolism. In addition we assessed the potential photoprotective effect of fish
      oil in light-sensitive patients. Thirteen patients with polymorphic light
      eruption received dietary supplements of fish oil rich in omega-3 polyunsaturated
      fatty acids for 3 months. At baseline and 3 months, the minimal erythema dose of
      UVB irradiation was determined, and a graded UVA challenge given to a forearm to
      assess the threshold dose for papule provocation. Suction blisters were raised on
      the other forearm, on control skin, and on skin irradiated with four times the
      minimal erythema dose of UVB 24 h previously, and blister fluid prostaglandin E2
      was measured by radioimmunoassay. Following 3 months of fish oil, the mean
      minimal erythema dose of UVB irradiation increased from 19.8 +/- 2.6 to 33.8 +/-
      3.7 mJ/cm2 (mean +/- SEM), p < 0.01. The UVA provocation test was positive in 10
      patients at baseline, and after 3 months nine of these showed reduced sensitivity
      to papule provocation, p < 0.001. Before fish oil, PGE2 increased from 8.6 (SEM
      2.1) ng/ml in control skin to 27.2 (11) ng/ml after UVB, p < 0.01. Following 3
      months of fish oil, PGE2 decreased to 4.1 (1) and 9.6 (2.4) ng/ml in control and
      irradiated skin, respectively, p < 0.05. Reduction of UV-induced inflammation by
      fish oil may be due, at least partially, to lowered prostaglandin E2 levels. The
      photoprotection against UVA-provocation of a papular response suggests a clinical
      application for fish oil in polymorphic light eruption.

PMID- 7561155
TI  - Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN
      gamma-treated keratinocytes and keratinocyte cell lines.
AB  - The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus
      derived bacterial superantigen, on expression of intercellular adhesion molecule
      1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human
      keratinocytes by flow cytometry, confocal microscopy, digital image processing,
      and reverse transcriptase-polymerase chain reaction. SEB significantly
      upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA
      DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but
      not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and
      pertussis toxins did not have the effect. The distribution of SEB and HLA-DR
      molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by
      confocal microscopy. Digital image processing analysis demonstrated that SEB
      induced a transient increase of intracellular calcium concentration only in the
      IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells
      with anti-major histocompatibility complex class II monoclonal antibody
      completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in
      the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse
      transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds
      to keratinocytes, presumably via major histocompatibility complex class II
      molecules such as HLA-DR, triggers calcium mobilization, and induces the
      synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders,
      SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to
      upregulate ICAM-1 expression, thus modulating the course of the inflammatory
      process.

PMID- 7561156
TI  - Anti-basement membrane autoantibodies in patients with anti-epiligrin cicatricial
      pemphigoid bind the alpha subunit of laminin 5.
AB  - Recent studies have identified a group of cicatricial pemphigoid patients who
      have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of
      disulfide-linked polypeptides closely related if not identical to laminin 5
      (formerly called kalinin, nicein, or BM600). To further understand the
      pathophysiology of blister formation in these patients, we have sought to
      identify the specific polypeptide(s) targeted by their autoantibodies.
      Comparative studies show that sera from these patients (nine of nine), P1E1
      monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti
      laminin 5 antibodies immunoprecipitate the same set of disulfide-linked
      polypeptides from media of biosynthetically radiolabeled human keratinocytes.
      Moreover, sera from eight of nine patients with anti-epiligrin cicatricial
      pemphigoid immunoblot the alpha subunit of laminin 5 but show no reactivity to
      its beta or gamma subunits. In addition, circulating IgG from a representative
      patient was affinity-purified against the alpha subunit of laminin 5 and shown to
      bind the dermal side of 1 M NaC1 split skin in the same manner as autoantibodies
      from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients
      with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5),
      epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus
      (n = 1) show no reactivity against any subunit of this laminin isoform in
      immunoprecipitation or immunoblot experiments. These findings correlate with
      prior reports showing that a monoclonal antibody directed against the alpha
      subunit of laminin 5 (i.e., laminin subunit alpha 3) induces detachment of human
      keratinocytes from extracellular matrix in vitro as well as epidermis from human
      skin in situ. Together, these studies suggest that laminin subunit alpha 3
      mediates attachment of basal keratinocytes to epidermal basement membrane and
      that autoantibodies directed against it may be pathogenic.

PMID- 7561157
TI  - Application of retinol to human skin in vivo induces epidermal hyperplasia and
      cellular retinoid binding proteins characteristic of retinoic acid but without
      measurable retinoic acid levels or irritation.
AB  - We investigated the clinical, histologic, and molecular responses of normal human
      skin to all-trans-retinol (ROL) application, compared to those induced by topical
      all-trans-retinoic acid (RA), and measured ROL-derived metabolites. Up to 1.6%
      ROL, 0.025% RA in vehicle (70% ethanol/30% propylene glycol), or vehicle alone
      were applied in a double-blind fashion to normal buttock skin and occluded for 4
      d. ROL produced from none to only trace erythema, which was clinically and
      statistically insignificant, whereas RA induced a significant 3.7-fold increase
      in erythema score compared to vehicle (n = 10, p < 0.01). However, ROL induced
      significant epidermal thickening (1.5-fold at 1.6% ROL, p < 0.01), similar to RA
      (1.6-fold at 0.025% RA, p < 0.01), relative to the vehicle. ROL, compared with
      vehicle, also increased mRNA levels of cellular retinoic acid binding protein
      (CRABP-II) and cellular retinol binding protein (CRBP) genes as determined by
      Northern analysis (5-6-fold and 6-7-fold, respectively) and riboprobe in situ
      hybridization. CRABP-II and CRBP protein levels were also higher following ROL
      than vehicle treatment, as measured by ligand binding (3.2-fold, p < 0.001; n =
      7) and Western analysis (3.6-fold, p < 0.003; n = 6), respectively. Epidermal
      retinyl ester (RE) content, measured after removal of stratum corneum, rose 240
      fold (p < 0.005, n = 5) by 24 h of ROL occlusion. RA content, however, was
      undetectable or detectable only at trace amounts in all samples obtained at 0, 6,
      24, and 96 h after ROL occlusion. Detectability of RA was not correlated with ROL
      treatment (compared to untreated normal skin, p = 0.86) or baseline skin ROL
      levels (average r = -0.1, p > 0.3). These data demonstrate that ROL application
      1) produces trace erythema not significantly different from vehicle, whereas RA
      causes erythema; 2) induces epidermal thickening and enhances expression of CRABP
      II and CRBP mRNAs and proteins as does RA; 3) causes marked accumulation of
      retinyl ester; and 4) does not significantly increase RA levels. Taken together,
      the data are compatible with the idea that ROL may be a prohormone of RA, because
      it produces changes in skin similar to those produced by RA but without
      measurable RA or irritation.

PMID- 7561158
TI  - Rapid spreading and mature hemidesmosome formation in HaCaT keratinocytes induced
      by incubation with soluble laminin-5r.
AB  - HaCaT cells, an immortalized keratinocyte line, incubated in plastic wells in the
      presence of conditioned medium from 804G cells adhered and spread rapidly in less
      than 30 min. In contrast, cells plated in fibroblast or keratinocyte conditioned
      medium adhered poorly and remained rounded at 30 min. Immunodepletion of 804G
      conditioned medium with polyclonal antisera to laminin-5r, but not control
      antisera, abolished rapid cell spreading. Electron microscopy of HaCaT cells
      spread by incubation in 804G conditioned medium, but not control medium, revealed
      mature hemidesmosomes after 24 h. Rapid spreading was also observed in wells
      precoated with 804G conditioned medium or 804G cell-deposited matrix, but not
      with fibronectin, vitronectin, or laminin-1. Immunoblotting of 804G conditioned
      medium with anti-laminin-5r antibodies unveiled polypeptides of 150, 140, 135,
      and 100 kDa, identical by electrophoretic mobility to immunoreactive polypeptides
      in 804G deposited matrix. Our results suggest that addition of laminin-5r in a
      soluble form is sufficient to promote rapid spreading and hemidesmosome assembly
      in keratinocytes. The mechanism of soluble laminin-5r action may include
      efficient surface "priming" for cell adhesion. Soluble laminin-5r may have a
      physiologic role in morphogenesis and repair of the epidermis and may be of use
      for therapeutic applications.

PMID- 7561159
TI  - Antiprotease activity in urine of patients with inflammatory skin disorders.
AB  - Polymorphonuclear leukocytes contain well-defined proteolytic enzymes in their
      azurophilic granules that can be released into tissues during inflammation,
      producing a localized excess of proteases that causes a protease-antiprotease
      imbalance with subsequent tissue destruction. The antiproteolytic compounds of
      the epidermis, such as the protease inhibitors elafin and antileukoprotease, are
      thought to counteract the proteolytic tissue damage. We investigated the urine of
      patients suffering from inflammatory skin conditions (e.g., erysipelas,
      psoriasis) for the presence of urinary antiprotease activities. Purification of
      elastase-inhibitory activities from pooled urine samples by cation exchange high
      performance liquid chromatography and preparative and analytical reverse-phase
      high-performance liquid chromatography yielded two different types of inhibitors.
      One was a cationic, acid-stable, and elastase-specific inhibitor of M(r) 6,000 by
      size-exclusion high-performance liquid chromatography. N-terminal amino acid
      sequence analysis of the first 28 residues showed identity with elafin, an
      elastase-specific inhibitor recently isolated from psoriatic scales. The second
      anti-protease activity was due to two forms of urinary bikunin, the inhibitory
      subunit of inter-alpha-inhibitor. Both bikunin fragments, with M(r) 4,000 and
      16,000, were identified by N-terminal amino acid sequence analysis of the first
      10 residues and were characterized by an antiproteolytic profile against human
      leukocyte elastase, cathepsin G, and trypsin. Urinary protease inhibitors may
      serve as diagnostic markers of inflammatory diseases.

PMID- 7561160
TI  - Differential down-regulation of protein kinase C subspecies in normal human
      melanocytes: possible involvement of the zeta subspecies in growth regulation.
AB  - Normal human melanocytes are often grown in vitro in the continuous presence of
      12-O-tetradecanoylphorbol-13-acetate (TPA) for growth in vitro. The expression of
      protein kinase C (PKC) subspecies, which are the major cellular receptors for
      phorbol esters, was examined in melanocytes after long-term treatment with TPA to
      investigate the role of PKC subspecies in TPA-dependent cell growth. The PKC
      enzyme activity detected in quiescent melanocytes was almost completely depleted
      in cells after incubation with 85 nM TPA for 48 h. Immunoblot analysis indicated
      that, among the PKC subspecies alpha, beta, delta, epsilon, and zeta expressed in
      quiescent cells, alpha-, beta-, delta-, and epsilon-PKC were significantly down
      regulated, whereas zeta-PKC remained at detectable levels in TPA-treated cells.
      TPA did not significantly affect the expression or subcellular distribution of
      zeta-PKC in melanocytes. Immunoprecipitation assay revealed that the enzyme
      activity of zeta-PKC was increased in both the cytosol and particulate cell
      fractions, but the increase was much greater in the latter. The activation of
      zeta-PKC lasted for 24 to 48 h after the addition of TPA; thereafter, zeta-PKC
      activity returned to basal levels. DNA synthesis was shown to change
      concomitantly with the activation of zeta-PKC in TPA-treated cells. These results
      indicate that TPA induces not only the down-regulation of alpha-, beta-, delta-,
      and epsilon-PKC, but also long-term activation of zeta-PKC in melanocytes, and
      that activation of zeta-PKC parallels the growth of normal human melanocytes.

PMID- 7561161
TI  - Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact
      and functional in acute wounds: the inhibitor protects fibronectin from
      degradation by chronic wound fluid enzymes.
AB  - Fluid obtained from chronic and acute wounds were examined for the presence of
      fibronectin, alpha 1-antitrypsin, and proteinases capable of degrading both
      proteins. Immunoblot analysis of fluids from ten chronic wounds revealed that
      fibronectin and alpha 1-antitrypsin were degraded in nine of ten samples. In
      contrast, both fibronectin and alpha 1-antitrypsin were intact in acute wound
      fluids. The degradation of the inhibitor and fibronectin occurred in the same
      wound fluids, and these two events correlated perfectly. Chronic or acute wound
      fluid proteins were coupled to benzamidine Sepharose 6B beads and incubated with
      fibronectin or alpha 1-antitrypsin. Chronic wound fluid proteins degraded
      fibronectin in the presence of ethylenediaminetetraacetate, leupeptin, cystatin,
      and pepstatin but not in the presence of phenylmethylsulfonyl fluoride. Acute
      wound fluids and normal human serum did not contain enzymes capable of degrading
      fibronectin. These data suggest that serine proteinases are responsible for
      fibronectin degradation in chronic wound fluids. Chronic wound fluids that
      contained degraded alpha 1-antitrypsin also contain proteinases capable of
      degrading alpha 1-antitrypsin from human serum. Acute wound fluids and normal
      human serum did not contain enzymes capable of degrading alpha 1-antitrypsin. The
      inhibitor from acute wound fluids bound to one of its targets, trypsin. In
      contrast, the fragment(s) of alpha 1-antitrypsin from chronic wound fluids did
      not bind trypsin. Chronic wounds associated with degraded fibronectin and the
      inhibitor contained ten- to forty-fold more elastase activity than acute wounds.
      The degradation of fibronectin by chronic wound fluid enzymes was inhibited by
      alpha 1-antitrypsin in a dose-dependent manner. Collectively, these results
      demonstrate that there are enzymes in chronic wounds that perturb the function of
      alpha 1-antitrypsin and allow fibronectin degradation by uninhibited serine
      proteinases.

PMID- 7561162
TI  - Suppression of keratinocyte growth factor expression by glucocorticoids in vitro
      and during wound healing.
AB  - We have recently demonstrated an important function of keratinocyte growth factor
      (KGF) in morphogenesis of epithelium and wound re-epithelialization. Furthermore,
      abnormalities in KGF expression or responsiveness are associated with wound
      healing defects. In this study we have analyzed the regulation of KGF expression
      during wound repair in glucocorticoid-treated mice that are characterized by
      severe wound healing abnormalities. Induction of KGF mRNA expression after skin
      injury was significantly reduced in these mice, whereas KGF receptor mRNA levels
      were only affected to a minor extent by glucocorticoid treatment. The reduced KGF
      expression during wound healing in steroid-treated animals is at least partially
      due to a direct effect of glucocorticoids on the KGF expressing mesenchymal
      cells, because treatment of cultured fibroblasts with dexamethasone reduced KGF
      mRNA levels in a time- and concentration-dependent manner. The inhibitory effect
      of glucocorticoids on KGF expression was compensated for by high levels of serum
      growth factors or pro-inflammatory cytokines, demonstrating that KGF expression
      is subject to positive and negative regulation. Thus it seems likely that a fine
      balance of various KGF-regulating factors is important for normal wound healing.

PMID- 7561163
TI  - Detection of the chemokine RANTES in cytokine-stimulated human dermal
      fibroblasts.
AB  - A novel family of structurally and functionally related polypeptides has recently
      been detected that are now referred to as chemokines. Within this family, a
      peptide with the acronym RANTES was shown to be chemotactic for memory T cells,
      monocytes, and eosinophilic and basophilic granulocytes, thus suggesting it plays
      an important role in chronic inflammatory and allergic diseases. Murine
      monoclonal antibodies as well as cDNA probes specific for human RANTES were
      raised and extensively characterized. With these antibodies, stimulated human
      dermal fibroblasts were shown to express intracellular RANTES peptide by
      immunocytochemistry. Furthermore, similar kinetics could be demonstrated in
      fibroblasts for both RANTES mRNA expression and secretion of RANTES peptide using
      Northern blot hybridization and sandwich-enzyme-linked immunosorbent assay,
      respectively. RANTES expression was induced upon stimulation with tumor necrosis
      factor-alpha as well as with interleukin-1 alpha and -beta in a concentration-
      and time-dependent manner. These results reinforce the role of both resident and
      circulating cells in the production and release of RANTES and their participation
      in inflammatory processes.

PMID- 7561165
TI  - Skin fibroblasts are the only source of nidogen during early basal lamina
      formation in vitro.
AB  - The purpose of this study was to determine whether nidogen, the linkage protein
      of the basal lamina, is of epidermal or dermal origin. The development of the
      basal lamina was studied in an in vitro skin model. Preputial fibroblasts seeded
      onto a nylon mesh attached, proliferated, and developed a rich extracellular
      matrix (dermal model). Preputial keratinocytes were added to the dermal model to
      form a keratinocyte dermal model that ultrastructurally resembled in many
      respects human skin. Ultrastructural analysis revealed early stages of dermal
      development, including an incomplete basal lamina, aggregates of dermal
      filamentous material connecting to the lamina densa, bundles of 10-nm
      microfibrils, formation of premature hemidesmosomes, anchoring filaments, and
      anchoring fibrils. The cell origin of nidogen was determined in the dermal model
      and in the epidermal and dermal components of the keratinocyte dermal model.
      Specific antibodies and a cDNA probe for nidogen were used for immunofluorescence
      microscopy, Western and Northern blots, and for in situ hybridization studies.
      Our data show that fibroblasts are the only source of nidogen during early basal
      lamina formation. Although fibroblasts can synthesize nidogen and deposit it in
      the dermal matrix, no basal lamina will form unless they are recombined with
      keratinocytes. This suggests that the epidermis plays a major regulatory role in
      the production and assembly of nidogen into the basal lamina.

PMID- 7561164
TI  - 2B4, a new member of the immunoglobulin gene superfamily, is expressed on murine
      dendritic epidermal T cells and plays a functional role in their killing of skin
      tumors.
AB  - Dendritic epidermal T cells (DETC), which are skin-specific members of the tissue
      resident gamma delta T-cell family, are characterized by their potential to kill
      selected tumor targets by a non-major histocompatibility complex (MHC)-restricted
      mechanism. We have recently identified a new receptor molecule, 2B4, that appears
      to be associated with non-MHC-restricted recognition of tumor targets by natural
      killer cells. The purpose of this study was to determine whether DETC express 2B4
      molecules, and, if so, to assess their functional roles in DETC-mediated killing
      of tumor targets. Short-term DETC lines as well as DETC freshly procured from
      skin expressed surface 2B4, as detected with a specific monoclonal antibody.
      Removal of interleukin (IL)-2 from DETC cultures caused substantial reduction in
      2B4 expression levels as well as a reduction in cytotoxic capacity against YAC-1
      targets in a standard 51Cr-release assay. Conversely, exposure to IL-2, but not
      to IL-7, elevated both 2B4 expression and cytotoxicity. To assess the functional
      roles played by surface 2B4, we pretreated DETC lines with anti-2B4 antibody and
      then tested for their killing potential. Anti-2B4, but not the control antibody,
      augmented their capacity to lyse YAC-1 targets (51Cr-release assays) and to
      disrupt the monolayers of Pam-212-transformed keratinocytes (visual assessment).
      Thus, we conclude that DETC express, in an IL-2-dependent manner, 2B4 molecules,
      which may play a unique role in the killing of skin-derived tumors.

PMID- 7561167
TI  - The primary cytotoxicity in ultraviolet-a-irradiated riboflavin solution is
      derived from hydrogen peroxide.
AB  - The cytotoxic action of near-ultraviolet (UVA) radiation on cultured mammalian
      cells is dependent upon oxygen, suggesting that reactive oxygen species are
      involved in the cellular action of the radiation. Flavins are thought to be an
      important chromophore for photo-induced skin injury. Irradiation of riboflavin
      with UVA radiation is known to produce singlet oxygen, superoxide anions, and
      triplet-state riboflavin radicals, which, however, are immediately quenched by
      many constituents of the human skin. If the chemical produces a long-lived
      reactive oxygen species, hydrogen peroxide (H2O2), after UVA radiation, its
      deleterious effect is not limited to its generation site. Thus, we investigated
      whether H2O2, is produced in UVA-irradiated riboflavin solution and whether it
      plays an important role in the cytotoxic action of the solution. The solution
      showed a marked cytotoxic effect when placed on human fibroblasts, and
      cytotoxicity was retained in the solution for at least 40 min after radiation.
      Most of the toxicity appeared to be derived from H2O2 produced in the solution,
      because the solution lost its cytotoxicity as a result of catalase treatment, and
      the resultant restoration of survival was almost complete. Under our conditions,
      two molecules of riboflavin were calculated to produce one molecule of H2O2 after
      UVA radiation.

PMID- 7561166
TI  - Insulin-like growth factor-I and epidermal growth factor regulate insulin-like
      growth factor binding protein-3 (IGFBP-3) in the human keratinocyte cell line
      HaCaT.
AB  - The human keratinocyte cell line HaCaT has a basal phenotype and secretes an
      insulin-like growth factor (IGF) binding protein, IGFBP-3, which modulates its
      IGF-I response. Keratinocytes are highly responsive to mitogenic stimulation by
      IGF-I and epidermal growth factor (EGF), but the effect of these growth factors
      on IGFBP secretion by keratinocytes is not known. We investigated the effects of
      IGF-I and EGF, as well as three other skin-growth regulators, retinoic acid,
      basic fibroblast growth factor, and dexamethasone, on mitogenic stimulation and
      IGFBP-3 production in HaCaT cells. IGF-I and EGF were strongly mitogenic, whereas
      retinoic acid, basic fibroblast growth factor, and dexamethasone were not
      significantly mitogenic. IGF-I increased the level of IGFBP-3 in cell-conditioned
      medium by up to twofold, whereas EGF caused a twentyfold reduction in IGFBP-3.
      Retinoic acid and basic fibroblast growth factor had only minor effects on IGFBP
      3 and dexamethasone had no effect. IGF-I stimulation of IGFBP-3 did not involve
      increases in IGFBP-3 mRNA; however, EGF, consistent with its effect on IGFBP-3
      protein, caused a fivefold reduction in IGFBP-3 mRNA. In summary, EGF profoundly
      inhibited IGFBP-3 synthesis in basal keratinocytes, whereas IGF-I increased IGFBP
      3 levels by a posttranscriptional mechanism. We hypothesize that by inhibiting
      IGFBP-3 production in basal keratinocytes, epidermal mitogens such as EGF might
      stimulate epidermal growth indirectly by increasing local IGF-I availability.

PMID- 7561168
TI  - Free sphingosines of human skin include 6-hydroxysphingosine and unusually long
      chain dihydrosphingosines.
AB  - Ceramides containing 6-hydroxysphingosine, a previously unknown long-chain base,
      have recently been found in human skin. The present study investigated whether
      human skin also contains 6-hydroxysphingosine as the free base. Human skin
      surface lipids were obtained by washing with ethanol. A fraction enriched in
      sphingoid bases was isolated by preparative thin-layer chromatography and reacted
      with 2,4-dinitrofluorobenzene. The resulting N-dinitrophenyl derivatives were
      separated by thin-layer chromatography into three components, the most polar of
      which accounted for 15% of the total. After acetylation of the hydroxyl groups
      and repurification, each component was examined by nuclear magnetic resonance
      spectroscopy. The spectrum of the most polar of the derivatives indicated that it
      was 6-hydroxysphingosine or homologues of that substance. The spectra of the
      other two derivatives were virtually identical to those of derivatives prepared
      from authentic sphingosine and dihydrosphingosine. The chain-length distributions
      of the skin sphingoid bases were examined by gas chromatography after conversion
      of the dinitrophenyl acetates to dinitrophenyl trimethylsilyl derivatives. The
      analysis showed that the sphingosines and 6-hydroxysphingosines ranged from 17 to
      22 carbons in length, with the 18- and 20-carbon species predominating.
      Surprisingly, the dihydrosphingosines included species with up to 26 carbons,
      with the 24-, 25-, and 26-carbon species accounting for about half of the total.
      Examination of the sphingoid bases of pig epidermis indicated that 6
      hydroxysphingosine was not present and that the major chain length in the
      dihydrosphingosines was the 22-carbon species.

PMID- 7561169
TI  - Reduced skin barrier function parallels abnormal stratum corneum lipid
      organization in patients with lamellar ichthyosis.
AB  - Most patients with autosomal recessive lamellar ichthyosis are known to have
      markedly impaired skin barrier function. We hypothesize that this may be due to
      imperfections in the composition and fine structure of the intercellular stratum
      corneum lipids. The aim of the present study was to test this hypothesis. To
      characterize the barrier properties in three female patients with lamellar
      ichthyosis, the following parameters were used and compared with those of healthy
      volunteers: transepidermal water loss, stratum corneum lipid profiles after
      topical acetone/ether extraction on the flexure side of the forearm, and small
      angle x-ray diffraction. The extracted lipids were separated using high
      performance thin-layer chromatography and quantified, and the ceramide profile
      was determined. Small-angle x-ray diffraction was used to obtain information on
      the molecular structure and organization of the intercellular lipid domains of
      stratum corneum using stratum corneum scales collected by scraping.
      Transepidermal water loss was significantly increased in all three patients.
      Lipid analysis showed significant differences in the relative amounts of ceramide
      fractions 2-3a-3b-4-5, free fatty acid-ceramide ratio, and free fatty acid
      cholesterol ratio. Small-angle x-ray diffraction showed smaller repeated
      distances of lipid bilayers in stratum corneum samples of the patients compared
      with the healthy volunteers. An additional diffraction peak was found in the
      patients compared with the healthy volunteers, which can be ascribed to
      crystalline cholesterol. These data suggest that there might be a relation
      between the impaired barrier function and stratum corneum lipid structural and
      composition changes.

PMID- 7561170
TI  - Microsatellite instability and loss of heterozygosity in melanoma.
AB  - Alterations in the repeat length of microsatellites have been identified recently
      in tumors arising in patients with hereditary nonpolyposis colon cancer and in
      several human sporadic tumors. We examined 40 sporadic melanomas and their
      corresponding nontumorous skin for microsatellite instability (MSI) and loss of
      heterozygosity (LOH) at chromosomes 2q, 3p25-26, 5q11.2-13.3, 5q21, 6q27, 9p21,
      9p22-pter, 17p12, 17p12-p11.1, and 18q23. Specific loci were amplified by
      polymerase chain reaction, electrophoresed on polyacrylamide gels, transferred
      onto nylon membranes, and hybridized with 33P-end-labeled oligonucleotides. MSI
      was observed in eight of 40 (20%) melanomas at one of 10 loci examined. LOH was
      found at chromosome region 9p21 in 40%, at 9p22 in 22%, and at 17p in 13% of the
      informative cases. Comparison between clinicopathologic features of patients with
      and without MSI revealed no obvious differences. LOH at 9p21 was observed only in
      lesions greater than 1.5 mm in depth, suggesting that it does not represent an
      early event in sporadic melanoma. Our results indicate that 1) MSI is a genetic
      alteration in a proportion of sporadic melanoma, which may reflect a defect in
      genes involved in DNA replication fidelity; and 2) LOH at chromosome region 9p21
      is a significant event in sporadic melanoma. The latter finding further supports
      the hypothesis that the 9p21 region may contain one or more tumor suppressor
      genes (e.g., MTS1/CDNK2) involved in the pathogenesis of melanoma.

PMID- 7561171
TI  - Keratin 14 gene mutations in patients with epidermolysis bullosa simplex.
AB  - Mutations in genes encoding the keratin intermediate filaments expressed in basal
      cells have been identified in some families with epidermolysis bullosa simplex as
      the proximate cause of the fragility. We have systematically scanned genomic
      sequences of one of these keratins, keratin 14, for mutations in patients from 49
      apparently independent kindreds using single-strand conformation polymorphism
      analysis. The ten mutations identified are clustered at three sites--the ends of
      the helices and the L12 linker region, mutation sites that have been identified
      in past, more limited studies. Early onset of blistering in these ten families is
      correlated with more widespread distribution of lesions.

PMID- 7561172
TI  - Susceptibility to local and systemic bacterial infections in intercellular
      adhesion molecule 1-deficient transgenic mice.
AB  - The contribution of intercellular adhesion molecule 1 (ICAM-1) during systemic
      and local bacterial infections was studied in transgenic ICAM-1-deficient and
      control mice that were injected intraperitoneally (ip) or intradermally (id) with
      Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. Mortality
      rates, blood cultures, white blood cell (WBC) counts and absolute neutrophil
      counts (ANCs) were obtained daily until cultures were sterile. Six and 24 h after
      injections, autopsies were done on randomly selected ip-inoculated mice and
      biopsies were done on randomly selected id-inoculated mice. Survival rates were
      similar. In ICAM-1-deficient mice, ip P. aeruginosa resulted in higher incidences
      of bacteremia at 24 h (P = .003) and 48 h (P = .002); id S. aureus resulted in
      larger skin lesions (P = .026). Leukocytosis persisted in ICAM-1-deficient mice 6
      h after ip injection of E. coli; however, WBC counts and ANCs in peritoneal fluid
      did not differ. Although the inflammatory responses were similar histologically
      in ICAM-1-deficient and normal mice, differences in site- and stimulus-specific
      susceptibilities were noted.

PMID- 7561173
TI  - Ixodes dammini as a potential vector of human granulocytic ehrlichiosis.
AB  - Little is known about the epidemiology and mode of transmission of the agent of
      human granulocytic ehrlichiosis (HGE). Analyses of an engorged female Ixodes
      dammini tick removed from an HGE patient and 101 field-collected I. dammini and
      Dermacentor variabilis from three Wisconsin counties for Borrelia burgdorferi and
      Ehrlichia phagocytophila/Ehrlichia equi DNA revealed that the patient tick and 7
      of 68 I. dammini ticks from Washburn County collected in 1982 and 1991 were
      positive for ehrlichial DNA; 10 ticks from the same collections were positive for
      B. burgdorferi. Two specimens (2.2%) were positive for both organisms. Serologic
      evidence for exposure to the agent of HGE or its relatives was detected in 3 of
      25 Lyme disease patients from the upper Midwest. These data argue that I. dammini
      is a common vector for transmission of both Lyme disease and HGE.

PMID- 7561174
TI  - Major outer membrane protein variants of Chlamydia trachomatis are associated
      with severe upper genital tract infections and histopathology in San Francisco.
AB  - Cervical and endometrial samples from 33 women with lower genital tract infection
      (LGTI) or pelvic inflammatory disease (PID) were evaluated for Chlamydia
      trachomatis major outer membrane protein gene (omp1) polymorphism. Polymorphism
      was correlated with symptoms, clinical findings, and histopathology. F, E, I, D,
      H, K, and G genotypes were represented. Thirty-seven genotyped samples (66%)
      displayed omp1 mutations compared with prototype sequences. Significantly, 7 of 7
      women with variant F infections had PID compared with 6 non-variant F infections
      in women with LGTI (P = .003). PID was defined by clinical findings or plasma
      cells on endometrial biopsy. Of interest, F variants were associated with
      histopathology. Eleven women (92%) with E genotypes were asymptomatic. Our data
      suggest that F variants are associated with symptomatic, severe endometrial
      disease, whereas E genotypes are associated with asymptomatic, milder infections.
      Detection of virulent genotypes may provide a prognostic indicator for serious
      sequelae. Larger studies are required to evaluate the molecular, immunologic, and
      epidemiologic basis for these findings.

PMID- 7561175
TI  - Anticryptococcal activity of NK cell-enriched peripheral blood lymphocytes from
      human immunodeficiency virus-infected subjects: responses to interleukin-2,
      interferon-gamma, and interleukin-12.
AB  - Anticryptococcal activity of highly purified NK cells from patients with either
      early asymptomatic or late-stage human immunodeficiency virus (HIV) infection
      proved to be markedly impaired; activity was reproducibly restored to normal
      levels by in vitro addition of exogenous interleukin-12 (IL-12). For these highly
      purified NK cells, responses to IL-2 and interferon-gamma (IFN-gamma) among HIV
      infected patients were variable, with only 2 of 8 exhibiting significant
      responses to IL-2 or IFN-gamma. In contrast, IL-2 and IFN-gamma consistently
      enhanced anticryptococcal activity of mixed lymphocyte populations, cells that
      more closely approximate the network likely to be operational in vivo.

PMID- 7561176
TI  - Effects of macrophage colony-stimulating factor on antifungal activity of
      mononuclear phagocytes against Aspergillus fumigatus.
AB  - The effects of recombinant human macrophage colony-stimulating factor (M-CSF) on
      antifungal activity of human monocytes (MNC), MNC-derived macrophages (MDM), and
      rabbit pulmonary alveolar macrophages (PAM) against Aspergillus fumigatus were
      studied. MNC-induced hyphal damage was augmented by incubation with M-CSF (P =
      .027); PAM-induced hyphal damage was moderately enhanced by M-CSF (P = .046).
      Phagocytosis of Aspergillus conidia by MDM and PAM was strongly enhanced by M-CSF
      (P < .01). MNC pretreated with M-CSF exhibited enhanced superoxide anion
      production in response to PMA (P = .026). This effect was not associated with
      increased levels of mRNA transcripts of the components of NADPH oxidase, the
      enzyme responsible for superoxide anion production. M-CSF augments antifungal
      activity of mononuclear phagocytes against both conidia and hyphae of Aspergillus
      fumigatus partly by enhancement of oxidation-dependent mechanisms and may have an
      important immunomodulatory role in prevention and treatment of invasive
      aspergillosis in leukopenic patients.

PMID- 7561177
TI  - Effect of prophylactic fluconazole on the frequency of fungal infections,
      amphotericin B use, and health care costs in patients undergoing intensive
      chemotherapy for hematologic neoplasias.
AB  - Fungal infections are a major problem in patients with hematologic malignancy.
      Attempts to reduce their frequency with antifungal agents have not been
      successful. A double-blind, controlled, single-center trial was conducted with 96
      consecutive patients undergoing 154 episodes of chemotherapy. Patients received
      400 mg of fluconazole or placebo until bone marrow recovery or initiation of
      intravenous amphotericin B infusions. End points were amphotericin B use, fungal
      infection, stable neutrophil count > 0.5 x 10(9)/L, toxicity precluding further
      fluconazole use, and death. By Kaplan-Meier estimation, the time to initiation of
      amphotericin B therapy was shorter in 76 patients treated with placebo than in 75
      treated with fluconazole (P = .003). Also, fluconazole reduced the number of
      febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs.
      9/76, P = .018). The frequency of deep mycoses (8/76 vs. 8/75) and outcome were
      unaffected. Fluconazole did not have a favorable effect on infection-related
      health care costs and was associated with prolonged severe neutropenia (P = .01).

PMID- 7561178
TI  - Successful prevention and treatment of babesiosis with atovaquone.
AB  - Atovaquone was evaluated for the prevention and treatment of babesiosis in
      hamsters. When atovaquone was administered before inoculation of 10(6) Babesia
      microti and continued for 8 days thereafter, 9 of 10 hamsters survived beyond 54
      days, but all untreated controls died within 12 days after inoculation.
      Quantitation of parasitemia showed a mean of 75% erythrocytes parasitized by day
      5 in controls, but atovaquone recipients never exceeded 0.7% of parasitized
      erythrocytes over 54 days of observation. Clindamycin plus quinine was also
      effective but less so than atovaquone. When treatment was not started until
      parasitemia became established, atovaquone in doses of 300, 150, and 80 mg/kg/day
      was effective in the recovery of all animals compared with 50% of those receiving
      10 mg/kg/day and 10% of untreated controls. With its remarkable safety record,
      atovaquone offers promise for clinical trials in babesiosis of both humans and
      lower animals.

PMID- 7561179
TI  - Impact of transmission intensity and age on Plasmodium falciparum density and
      associated fever: implications for malaria vaccine trial design.
AB  - To facilitate design of vaccine trials, malaria was studied in 6-month- to 6-year
      old Kenyans during high (HI) and low intensity transmission seasons. During 84
      days after cure, exposure to infected mosquitoes was 9-fold greater in the HI
      group, yet incidence of P. falciparum infection was increased only 2-fold, with
      no age effect. The density of recurrent P. falciparum was 14-fold greater in the
      HI group, and there was a striking association between age and parasitemia > or =
      5000/microL. Fever was the only clinical manifestation attributable to
      parasitemia and only when the parasite density was > or = 5000/microL. Sixty-four
      percent of children with > or = 20,000 parasites/microL versus 10% with 1
      4999/microL were febrile when parasitemic. Recurrent P. falciparum infection as a
      vaccine trial end point can be studied year-round among children < or = 6 years
      [corrected] in western Kenya. However, high-grade parasitemia (> or = 5000 or
      20,000/microL) with or without elevated temperature will be optimally studied in
      the high transmission season among children < 2 years.

PMID- 7561180
TI  - Identification of Leishmania chagasi antigens recognized by human lymphocytes.
AB  - Preparative SDS-PAGE followed by electroelution was used to separate proteins of
      Leishmania chagasi promastigotes into 67 fractions. These fractions were tested
      for the ability to stimulate proliferation of peripheral blood mononuclear cells
      from healthy immune donors who were treated previously for visceral leishmaniasis
      and from nonimmune controls. The proliferative responses elicited by these
      proteins varied among individuals. The 69-kDa protein fraction contained a
      fragment with sequence similarity to the 70-kDa heat-shock protein. Fragments of
      the 46- and 41-kDa fractions had sequences not present in the National Biological
      Research Foundation data bank. These data suggest that a successful subunit
      vaccine may require multiple parasite antigens. The identification of antigens
      that elicit human T cell responses is an important step toward understanding the
      immunology of L. chagasi infection and ultimately in the development of a
      vaccine.

PMID- 7561181
TI  - Review: granulocyte colony-stimulating factor--role and relationships in
      infectious diseases.

PMID- 7561182
TI  - Parvovirus B19 infection in hospital workers: community or hospital acquisition?
AB  - A suspected nosocomial outbreak of parvovirus B19 infection in a maternity ward
      was investigated in February 1994. Questionnaires were administered and sera
      collected from maternity ward staff (n = 91), other ward staff in the same
      hospital (n = 101), and maternity ward staff at a nearby hospital (n = 81). Blood
      donors (n = 265) were used as community controls. Recent infection (parvovirus
      B19 IgM positivity) in susceptible persons (parvovirus B19 IgG-negative or IgM
      positive) was common among all 4 groups (23%-30%). This high rate of recent
      infection occurred during a large community outbreak of fifth disease.
      Environmental samples collected from a room where a stillborn parvovirus B19
      infected fetus was delivered were positive for parvovirus B19 DNA. Thus, this
      suspected nosocomial outbreak actually reflected transmission outside the
      hospital, but contaminated environmental surfaces were identified as one
      potential source for transmission of parvovirus B19.

PMID- 7561183
TI  - Investigation of hepatitis B virus transmission in a health care setting:
      application of direct sequence analysis.
AB  - An epidemiologically linked cluster of hepatitis B virus (HBV) infections was
      investigated using HBV DNA amplification by a nested polymerase chain reaction
      with primers complementary to the region around the immunodominant a determinant
      of the surface gene, part of the X and core genes, and precore region and direct
      nucleotide sequence analysis. The cluster, in which 2 persons died of fulminant
      hepatitis, comprised 1 blood donor, 2 patients, and 2 health care workers. The
      Kimura two-parameter method was used to compare variance among the cluster with
      that in the control samples, which were collected from 7 patients infected with
      the same HBV subtype. Significantly less variation occurred within the cluster
      than in the control group (unpaired t test, P < .05). In an unrooted phylogenetic
      tree analysis, the 5 study samples formed a cluster distinct from the controls.
      This direct molecular approach of analyzing conserved regions of the HBV genome
      differentiated between viruses involved in HBV transmission events.

PMID- 7561184
TI  - Risk factors for postcoital bleeding among women with or at risk for infection
      with human immunodeficiency virus.
AB  - Risk factors for postcoital bleeding were examined in 475 women who were enrolled
      in a study of heterosexual transmission of human immunodeficiency virus (HIV). In
      bivariate analyses, history of sexually transmitted diseases (STDs; P = .03), HIV
      infection (P = .008), and dyspareunia or pain during intercourse (P = .0001) were
      significant risk factors. In multivariate analysis, the two latter factors
      remained significant (for HIV, odds ratio [OR] = 2.1, P = .02, 95% confidence
      interval [CI] = 1.1-4.0; for dyspareunia, OR = 3.5, P < .001, 95% CI = 1.8-6.6),
      as did the interaction term of STD history and heavy smoking (OR = 2.4, P = .02,
      95% CI = 1.2-5.0). Pain during intercourse was the strongest predictor of
      postcoital bleeding but may be part of the same phenomenon. Similarly, because
      this study relied on cross-sectional data, the direction of the causal pathway
      linking HIV to postcoital bleeding cannot be established. However, these data
      suggest that smoking, a modifiable risk factor, may increase risk of postcoital
      bleeding and contribute to susceptibility for HIV and other STDs.

PMID- 7561185
TI  - Detection of herpesvirus DNA by nested polymerase chain reaction in cerebrospinal
      fluid of human immunodeficiency virus-infected persons with neurologic disease: a
      prospective evaluation.
AB  - A nested polymerase chain reaction-based method was used prospectively to detect
      herpesvirus DNA in cerebrospinal fluid (CSF) from 111 patients with AIDS, 39 of
      whom had a suspected diagnosis of cytomegalovirus (CMV)-associated neurologic
      disease (patients with encephalopathy, polyradiculopathy, or peripheral
      neuropathy) and 72 who had alternative diagnoses. CSF from 24 (62%) of the
      patients with suspected CMV-associated disease had detectable CMV DNA compared
      with only 8 (11%) of the patients with other diagnoses. Varicella-zoster virus
      DNA was detected in CSF from 3 patients (2 with myelitis and 1 with
      encephalitis), all of whom had recent cutaneous zoster. No CSF specimen contained
      detectable herpes simplex virus type 1 DNA, and none of the patients with
      myelitis had detectable herpes simplex virus type 2 DNA in CSF. This study
      demonstrates a significant association between detectable CMV DNA in CSF and
      suspected CMV-associated neurologic disease in patients with AIDS.

PMID- 7561186
TI  - Quantitative relationship of circulating p24 antigen with human immunodeficiency
      virus (HIV) RNA and specific antibody in HIV-infected subjects receiving
      antiretroviral therapy. The RV43 Study Group.
AB  - To better understand the biologic meaning and potential clinical utility of p24
      antigen measurements in human immunodeficiency virus (HIV) infection, p24 antigen
      and antibody and HIV RNA were quantitated in parallel. Specimens (n = 311) were
      analyzed from 74 participants in a zidovudine treatment study. Parallel antigen
      and RNA measurements revealed the frequent occurrence of two types of discordant
      results. First, p24 antigen was often not detected in samples with high antibody
      levels even when > 10(6) RNA copies/mL were present. Second, in specimens in
      which p24 antigen was detected, the concentration was greater than expected on
      the basis of HIV RNA values. These results suggest that optimal use of serum p24
      antigen values will require consideration of both specific antibody levels and
      non-virion associated antigen.

PMID- 7561188
TI  - Higher expression levels of alternatively spliced pX mRNA in human T lymphotropic
      virus type I asymptomatic carriers positive for antibodies to p40tax protein.
AB  - cDNA of human T lymphotropic virus type I (HTLV-I) pX gene mRNA expressed in
      peripheral blood lymphocytes of asymptomatic carriers was sequenced. One cDNA
      clone contained a novel splicing acceptor site, indicating an unidentified form
      of pX mRNA: pX delta 17 delta 37. All 21 asymptomatic carriers expressed some
      level of alternatively spliced pX mRNA (pX, pX delta 17, p21rex, orfII, or pX
      delta 17 delta 37). pX and pX delta 17 were the dominant mRNA species among the
      five pX mRNAs. All pX mRNAs but orfII correlated significantly with amounts of
      provirus DNA (P < .05). Levels of provirus DNA and pX mRNAs were significantly
      higher in anti-p40tax-positive carriers than in negative ones. These observations
      suggest that the pX mRNAs are expressed ubiquitously, with a complex pattern of
      splicing, and that the presence of anti-p40tax may serve as a marker for a higher
      virus load and viral replication levels in asymptomatic HTLV-I carriers.

PMID- 7561187
TI  - Elevated levels of iC3b and C4d, but not Bb, complement fragments from plasma of
      persons infected with human T cell leukemia virus (HTLV) with HTLV-I-associated
      myelopathy/tropical spastic paraparesis.
AB  - Plasma levels of complement (C) fragments iC3b, C4d, and Bb from human T cell
      leukemia virus (HTLV)-positive subjects with HTLV-I-associated myelopathy
      (HAM)/tropical spastic paraparesis (TSP) were analyzed by EIA. Both iC3b and C4d
      levels were significantly elevated in persons with HAM/TSP. These levels were
      similar to those in patients with human immunodeficiency virus (HIV) infection or
      rheumatoid arthritis (RA), who are known to have increased C fragments. Bb levels
      in persons with HAM/TSP wer unaffected, suggesting that C activation occurred
      only via the classical pathway. This differed from findings in HIV-infected or RA
      patients, who had elevated levels of Bb. The results showed an increase in C
      activation in persons with HAM/TSP and activation via the classical pathway,
      likely mediated by virus or immune complexes. It is possible that the C
      activation observed in these subjects contributed to the inflammatory
      pathogenesis of HAM/TSP.

PMID- 7561189
TI  - Cytotoxic T lymphocyte responses to a liposome-adjuvanted influenza A virus
      vaccine in the elderly.
AB  - This randomized double-blind study evaluated cytotoxic T lymphocyte (CTL)
      responses of elderly volunteers after parenteral immunization with either
      liposome-adjuvanted (n = 23) or control subvirion (n = 26) vaccine containing
      detergent-split influenza A/Taiwan/1/86 (H1N1) virus. Peripheral blood
      mononuclear cells obtained 0, 2, and 12 weeks after vaccination were stimulated
      in vitro with influenza A (H1N1) virus-infected autologous cells and then assayed
      for influenza virus-specific cytotoxicity using autologous virus-infected target
      cells. CTL responses to vaccination exhibited influenza A virus heterosubtypic
      cross-reactivity and were mediated primarily by CD8+ effector cells. Anti
      influenza virus CTL activity was enhanced to a significantly greater extent by
      the liposome vaccine than by the control subvirion vaccine. It remains to be
      established whether the advantage of a liposomal formulation in terms of an
      improved CTL response is relevant to vaccine protective efficacy.

PMID- 7561190
TI  - IgG subtype is correlated with efficiency of passive protection and effector
      function of anti-herpes simplex virus glycoprotein D monoclonal antibodies.
AB  - IgG subclasses differ in their effector functions in a variety of in vitro
      assays. To assess the effect of antibody subclass differences on in vivo
      protective efficacy against herpes simplex virus (HSV), a series of subclass
      switch mutants was made from an anti-HSV glycoprotein D monoclonal antibody.
      Purified antibody was examined for the ability to protect against HSV-2 challenge
      in mice. IgG2a was found to be more effective than IgG1. This correlated both
      with activity in antibody-dependent cell-mediated cytotoxicity and with
      efficiency of complement-mediated neutralization. These data suggest that
      optimization of passive immunization against HSV requires consideration of
      antibody subclass.

PMID- 7561191
TI  - Comparison of cotton and cotton/rayon tampons for effect on production of toxic
      shock syndrome toxin.
AB  - Studies were done to compare tampons made solely of cotton and made of both
      cotton and rayon for effect on growth of Staphylococcus aureus and production of
      toxic shock syndrome toxin-1 (TSST-1). Under stationary in vitro conditions in
      which tampons were either oversaturated or 50% saturated with culture media, the
      same amount of or more TSST-1 was made with cotton tampons than with cotton/rayon
      tampons. Similarly, when tested with the tampon sac method, cotton tampons
      yielded the same amount of or more toxin than did the cotton/rayon tampons.
      Bacterial cell numbers generally paralleled toxin production. These data indicate
      that cotton tampons neither prevent TSST-1 production nor significantly adsorb
      toxin onto the fibers to make toxin unavailable to cause toxic shock syndrome, in
      contrast to results of a previous study.

PMID- 7561192
TI  - Nasopharyngeal antibodies to pneumococcal capsular polysaccharides in children
      with acute otitis media.
AB  - Antibodies to pneumococcal capsular polysaccharides were measured by EIA in acute
      and convalescent-phase nasopharyngeal aspirates from 120 children with acute
      otitis media. Nasopharyngeal IgM- and IgG-class antibodies were rare, whereas IgA
      was detected more often, occurred independently from serum IgA, and correlated
      with the presence of the secretory component in pneumococcal antibody, indicating
      local production of IgA. Thirty-four percent of the children with pneumococci in
      middle ear fluid developed a nasopharyngeal IgA response to the polysaccharide
      pool of serotypes 6B, 14, 19F, and 23F compared with 7% of the children with
      pneumococci only in the nasopharynx or not found at all (P = .004). The responses
      were observed in children of all ages, the youngest 6 months of age. This
      supports the hypothesis that mucosal immunity to bacterial polysaccharides
      matures earlier than systemic immunity.

PMID- 7561193
TI  - Escherichia coli endotoxin-mediated endothelial injury is modulated by
      glutathione ethyl ester.
AB  - The mechanisms involved in endotoxin-induced endothelial injury are not fully
      understood. Oxidant stress is thought to play a role in cell damage after
      endotoxin exposure. Glutathione may ameliorate these affects. Glutathione ethyl
      ester (GSE) was used in bovine pulmonary artery endothelial cell (BPAEC) cultures
      to determine the potential for attenuation of endotoxin-induced injury. GSE (0.05
      25 mM) was preincubated with BPAEC for 4 h before endotoxin exposure. Fresh media
      containing GSE and Escherichia coli endotoxin (0.05 microgram/mL) were then
      placed on the BPAEC and incubated for 18 h. GSE, at doses of 5 and 25 mM,
      attenuated endotoxin-induced injury, as reflected by a significant reduction in
      lactate dehydrogenase release. This was paralleled by a significant increase in
      endotoxin-stimulated prostaglandin E2 and prostacyclin release. Thus, GSE
      attenuates endotoxin-induced injury of BPAEC in culture and alters BPAEC
      prostaglandin metabolism.

PMID- 7561194
TI  - A university outbreak of Escherichia coli O157:H7 infections associated with
      roast beef and an unusually benign clinical course.
AB  - An outbreak of Escherichia coli O157:H7 infections occurred after a graduation
      banquet at a university in Wisconsin. Sixty-one (32%) of 193 banquet attendees
      developed a gastrointestinal illness; 2 were hospitalized, none developed
      hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura, and none died.
      The spectrum of illness was unusually mild, with 61% of ill persons reporting
      nonbloody diarrhea. A strain of E. coli O157:H7, indistinguishable from the
      outbreak strain by toxin type, plasmid profile, and pulsed-field gel
      electrophoresis, was isolated from an unopened package of an uncooked round of
      beef from the original shipment of meat. An investigation suggested that both
      undercooked roast beef and salad cross-contaminated with beef were vehicles of
      transmission. These findings demonstrate that meat from beef cattle may transmit
      E. coli O157:H7, and such infections among young to middle-aged adults may be
      mild and may often go undetected.

PMID- 7561195
TI  - Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae
      O1.
AB  - Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor
      Inaba strain by deleting the cholera toxin genetic element, introducing the gene
      encoding cholera toxin B subunit into recA, and screening for nonmotility. In a
      controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No
      vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal
      antibody titers. One month later, 5 vaccinees and 5 control volunteers were
      challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea
      (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1
      with approximately 1.0 L; this latter volunteer had not developed a significant
      vibriocidal immune response to vaccination. Peru-15 shows promise as a single
      dose, oral cholera vaccine that is safe, immunogenic, and protective.

PMID- 7561196
TI  - High-resolution genotyping of Campylobacter coli identifies clones of
      epidemiologic and evolutionary significance.
AB  - Campylobacter coli strains from clinical and other sources were examined in terms
      of O (heat-stabile; HS) serotype and by several molecular typing techniques.
      Restriction fragment length polymorphism (RFLP) around the three 16S rRNA genes
      revealed 10 variants, none found in Campylobacter jejuni. RFLP analysis of a
      polymerase chain reaction amplicon generated from the flagellin gene (flaA)
      yielded 11 polymorphism groups, some of them linked to HS serotypes. Enlarged
      flaA genes, contributing three further polymorphisms, were detected in strains
      isolated from fresh water. Restriction of the genome with SmaI and pulsed-field
      gel electrophoresis was the most discriminatory typing method, detecting 33
      macrorestriction profiles that subtyped within HS serotypes. The coincidence of
      HS serotype and the three genotypic markers identified clonal lines of
      evolutionary and epidemiologic significance.

PMID- 7561197
TI  - Helicobacter pylori infection and foreign travel.
AB  - Seroprevalence of antibodies to Helicobacter pylori is generally higher in
      developing than in developed countries. The route of transmission of H. pylori is
      unknown but is most commonly assumed to be fecal-oral. Gastroenteritis in a
      person traveling to developing countries is often a marker of exposure to fecally
      contaminated food or water. Of 133 initially seronegative young Swedes traveling
      to developing countries for a total of 16.4 years, of whom 102 reported having
      had at least one episode of gastroenteritis, not one seroconverted. This rate is
      lower than in studies of residents in developed countries and casts some doubt on
      the theory of fecal-oral transmission via a common source as an important mode of
      transmission of infection with Helicobacter pylori.

PMID- 7561198
TI  - Thalidomide inhibits tumor necrosis factor-alpha production by lipopolysaccharide
      and lipoarabinomannan-stimulated human microglial cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pathogenic factor in bacterial
      meningitis. The effect of thalidomide on TNF-alpha production by microglia, the
      resident macrophages of the brain, was evaluated. In primary human fetal
      microglial cell cultures stimulated with lipopolysaccharide or lipoarabinomannan,
      thalidomide inhibited TNF-alpha release in a dose-dependent manner. The
      inhibitory effect of thalidomide was similar to that of dexamethasone, although
      expression of TNF-alpha mRNA in microglial cells was reduced only by thalidomide.
      The results of this in vitro study suggest that thalidomide could have
      therapeutic potential in gram-negative bacterial and tuberculous meningitis.

PMID- 7561200
TI  - Prevalence of Bartonella henselae antibodies in pet cats throughout regions of
      North America.
AB  - Cat exposure has been directly associated with the development of human
      Bartonella henselae infections, resulting in cat-scratch disease, bacillary
      angiomatosis, or bacteremia. The prevalence of serum antibody titers to B.
      henselae was determined for selected pet cats from 33 geographic locations
      throughout the United States and several areas in western Canada. Seroprevalences
      paralleled increasing climatic warmth (P < .02) and annual precipitation (P <
      .03). These warm, humid areas with the highest seroprevalence would also have the
      highest number of potential arthropod vectors. The southeastern United States,
      Hawaii, coastal California, the Pacific Northwest, and the south central plains
      had the highest average prevalences (54.6%, 47.4%, 40.0%, 34.3%, and 36.7%,
      respectively). Alaska, the Rocky Mountain-Great Plains region, and the Midwest
      had low average prevalences (5.0%, 3.7%, and 6.7%, respectively). Overall, 27.9%
      (175/628) of the cats tested were seropositive. The seroprevalence of B. henselae
      in cats varies throughout the United States and appears to be influenced by
      climate.

PMID- 7561199
TI  - Transmission and passage in horses of the agent of human granulocytic
      ehrlichiosis.
AB  - The human granulocytotropic ehrlichia and Ehrlichia equi produce similar diseases
      in their respective host species (humans, horses). Currently, the phylogenetic
      and biologic relationships of these 2 uncultured pathogens remain unclear.
      Previous studies have revealed nucleotide sequence similarity approaching
      identity at the level of the 16S ribosomal RNA gene. To investigate the biologic
      similarities of these 2 ehrlichiae, the susceptibility of horses to the human
      agent was tested by intravenous inoculation of infected human blood. The results
      demonstrate that the human granulocytotropic ehrlichia produces a disease in the
      horse indistinguishable from that caused by E. equi, providing biologic evidence
      that these 2 organisms are highly related and potentially conspecific. It is
      possible that cases of human illness now attributed to human granulocytotropic
      ehrlichia may in fact be caused by 1 or more strains of an ehrlichia known
      chiefly as an equine pathogen.

PMID- 7561201
TI  - Mycobacterium avium complex in macaques with AIDS is associated with a specific
      strain of simian immunodeficiency virus and prolonged survival after primary
      infection.
AB  - Mycobacterium avium complex (MAC) in simian immunodeficiency virus (SIV)-infected
      macaques is a frequent opportunistic infection that shares many features with the
      condition in human AIDS patients. A retrospective analysis of necropsies on 135
      macaques with SIV-induced simian AIDS that received neither antiretroviral nor
      antimicrobial therapy revealed that 17% (23/135) were infected with MAC. MAC
      developed in 31.3% (21/67) of the animals inoculated with uncloned SIVmac251
      versus 1.9% (1/53) and 6.7% (1/15) of the animals inoculated with the molecular
      clones SIVmac239 and SIVmac239/316EM, respectively (P = .001). This is the first
      example in which the risk of infection with a specific opportunistic organism was
      affected by the infecting strain of immunodeficiency virus. In addition, animals
      with MAC had a longer mean survival after primary infection and lower CD4 cell
      counts at death than animals that did not develop this opportunistic infection.
      The SIV-inoculated macaque is a valuable model in which to study the pathogenesis
      of MAC in the immunocompromised host.

PMID- 7561202
TI  - A simplified new assay for assessment of fungal cell damage with the tetrazolium
      dye, (2,3)-bis-(2-methoxy-4-nitro-5-sulphenyl)-(2H)-tetrazolium-5-carboxanil ide
      (XTT).
AB  - Studies of antimycotic host defenses have been limited by the paucity of rapid,
      reproducible quantitative assays for fungal cell damage. Prior studies defined a
      colorimetric method that uses MTT, a tetrazolium dye, to quantify
      polymorphonuclear leukocyte (PMNL)-mediated damage to fungi. These relatively
      simple, rapid, and reproducible assays require cumbersome extraction of
      precipitated MTT-formazan and high cell densities to overcome relatively low
      sensitivity. In experiments that compared assays with MTT and another tetrazolium
      dye, 2,3-bis-(2-methoxy-4-nitro-5-sulphenyl)-(2H)-tetrazolium-5-+ ++carboxanilide
      (XTT), estimates of damage to Aspergillus fumigatus hyphae by human PMNL were
      similar with both dyes. However, XTT reduction was more rapid and sensitive,
      yielding accurate results with fewer organisms and PMNL. The water-soluble XTT
      formazan product also simplified measurements by eliminating the need for solvent
      extraction steps that are obligatory in MTT assays. Thus, XTT is advantageous for
      quantitative assessment of fungal cell damage, although MTT remains useful for
      assessing fungal cell viability by direct microscopic visualization of
      precipitated formazan.

PMID- 7561203
TI  - Drug cytotoxicity assay for African trypanosomes and Leishmania species.
AB  - The trypanosomes and Leishmania species are parasitic protozoa that afflict
      millions of people throughout the world. If not treated, African trypanosomiasis
      and visceral leishmaniasis are fatal. The available drugs are severely limited by
      toxicity, marginal efficacy, the requirement for parenteral administration, and
      spreading drug resistance. In this study, a spectrophotometric assay was
      developed and validated for measuring the cytotoxicity of test compounds against
      axenically cultured bloodstream-form Trypanosoma brucei (African trypanosomes)
      and promastigotes of Leishmania donovani. Enzymatic hydrolysis of p-nitrophenyl
      phosphate, monitored by a microtiter plate reader, is a reliable surrogate for
      parasite cell counts. The assay is simple, inexpensive, and highly reproducible.
      The coefficient of variation for EC50 values is < 10% for determinations obtained
      over several months. This method permits the rapid screening of candidates for
      much-needed new drugs against these parasites.

PMID- 7561204
TI  - Evaluation of a two-phase scid mouse model preconditioned with anti-interferon
      gamma monoclonal antibody for drug testing against Cryptosporidium parvum.
AB  - One 1-mg injection of anti-interferon-gamma monoclonal antibody (anti-IFN-gamma
      MAb) into newly weaned scid mice 2 h before challenge with Cryptosporidium parvum
      oocysts markedly exacerbated the course of the infection for > or = 47 days,
      compared with challenged mice that received an equivalent dose of irrelevant MAb.
      Oocyst excretion in feces started 4-6 days after challenge and continued at high
      levels for > or = 47 days. Loss of body weight was also apparent. The extent and
      distribution of mucosal infection were profound, involving the stomach and
      several segments of the small and large intestines. The acute phase, which
      involved infection of the gut, was during the first 25 days after challenge. The
      following chronic phase consistently involved, in addition, infection of the
      hepatobiliary tract. The acute phase is a useful model in which to test luminally
      active drugs, while the chronic phase may be used in the future to test drugs
      that are active against hepatobiliary tract infections as well.

PMID- 7561205
TI  - Cyclical peaking of streptococcal infections: recent and historical trends.

PMID- 7561206
TI  - Hantavirus pulmonary syndrome associated with entering or cleaning rarely used,
      rodent-infested structures.

PMID- 7561207
TI  - Impaired hepatic protein synthesis in AIDS patients with low vitamin A levels.

PMID- 7561208
TI  - Anticryptosporidial activity of paromomycin.

PMID- 7561209
TI  - Antiinflammatory and proinflammatory cytokines in patients with severe sepsis.

PMID- 7561210
TI  - Identification of the respiratory syncytial virus-induced immunosuppressive
      factor produced by human peripheral blood mononuclear cells in vitro as
      interferon-alpha.
AB  - Respiratory syncytial virus (RSV) can inhibit the proliferative response of human
      peripheral blood mononuclear cells (PBMC) in vitro. This inhibition is mediated
      by an extracellular RSV-induced factor. In the present study, the factor was
      clearly identified as interferon (IFN)-alpha. The RSV-induced IFN-alpha bound
      strongly to PBMC and inhibited the anti-RSV proliferative response only when
      added within the first few days of stimulation. There was, however, no
      concomitant decrease in the production of interleukin (IL)-2 nor in the cell
      surface expression of CD25, CD71, and HLA-DR. Inhibition by RSV-induced IFN-alpha
      was unrelated to the levels of IL-1, -2, and -6 or of IFN-gamma induced by RSV in
      vitro or to the presence of IL-1 inhibitor, tumor necrosis factor-alpha,
      prostaglandin, or IL-10. Immunosuppression by IFN-alpha may significantly affect
      the outcome of infection and reinfection with RSV.

PMID- 7561211
TI  - Viremia, fecal shedding, and IgM and IgG responses in patients with hepatitis E.
AB  - Viremia, fecal shedding and antibody responses to hepatitis E virus (HEV)
      infections are poorly understood. To better characterize HEV infections, these
      responses were examined in 67 patients with acute markers for hepatitis E who
      were admitted to the Infectious Disease Hospital in Kathmandu, Nepal in 1993. A
      single stool and multiple sera from each patient were examined using polymerase
      chain reaction to detect HEV RNA. Sera were also examined for antibodies to HEV.
      Viremia, fecal shedding, and IgM and IgG to HEV were detected in 93%, 70%, 79%,
      and 87% of 67 patients, respectively. Viremia or fecal shedding (or both) were
      detected in 14 patients from whom IgM and IgG to HEV were not detected. Viremia
      lasted at least 2 weeks in nearly all subjects and at least 39 days in 1 subject.
      Our results suggest that viremia is a common occurrence in patients infected with
      HEV.

PMID- 7561212
TI  - Hepatitis C virus genotypes 1 and 2 respond to interferon-alpha with different
      virologic kinetics.
AB  - Responses of patients infected with chronic hepatitis C virus (HCV) to interferon
      alpha (IFN-alpha) treatment were studied. HCV genotypes were determined by
      molecular and serologic techniques. Levels of HCV viremia were determined by
      quantitative reverse transcription-polymerase chain reaction. Infection with HCV
      genotype 2 or low pretreatment HCV viremia levels in subjects infected with
      genotype 1 were associated with favorable (complete and sustained) responses (CR
      SR; P < .001) to IFN-alpha treatment. HCV viremia levels in genotype 2 infection
      were significantly lower (P < .05) than in genotype 1 infection. The reduction
      rates of serum HCV RNA levels were four times higher in patients with genotype 2
      infection than in those infected with genotype 1. The proportion of patients with
      CR-SR who experienced virologic relapse after completion of IFN-alpha treatment
      was higher for those infected with genotype 1. The proportion of patients with CR
      SR and genotype 1 infection increased linearly in accordance with increases in
      single or total IFN-alpha dose.

PMID- 7561213
TI  - Failure of high-dose acyclovir to prevent cytomegalovirus disease after
      autologous marrow transplantation.
AB  - In a retrospective study, the strategy of giving high-dose acyclovir (500 mg/m2
      every 8 h intravenously) from day 5 before transplantation to day 30 after
      transplantation was evaluated in 266 cytomegalovirus (CMV)-seropositive autograft
      recipients. the incidence of CMV pneumonia was compared with that in 85 control
      patients who did not receive high-dose acyclovir. There was no significant
      difference in the incidence of CMV pneumonia between groups at day 100 (Kaplan
      Meier estimates, 6.3% [acyclovir] vs. 7.7% [controls], P = .63) and day 200 after
      transplantation (7.6% vs. 13.1%, P = .32). The overall rate of patients who
      presented with CMV disease without preceding excretion from blood, urine, or
      throat was 77%. CMV pneumonia was fatal in 9 (56%) of 16 acyclovir recipients
      compared with 5 (63%) of 8 controls (P = 1.0). Survival after transplantation was
      not different between groups (P = .68). Thus, high-dose acyclovir does not appear
      to be effective for prevention of CMV disease after autologous transplantation.

PMID- 7561214
TI  - Effect of passive antibody on congenital cytomegalovirus infection in guinea
      pigs.
AB  - Cytomegalovirus (CMV) is the most common congenital viral infection, but little
      is known about the protective immune mechanisms. The guinea pig (gp) model of
      congenital CMV was used to evaluate the effects of passive antibody given to
      pregnant dams on pup survival. Dams received three doses of high-titer gpCMV or
      control antibody on days -3, -1, and +7, or +1, +3, and +7, in relation to gpCMV
      challenge. gpCMV was inoculated in the late second to early third trimester at
      three different doses. Compared with controls, gpCMV antibody begun before gpCMV
      challenge significantly increased pup survival from 14% to 52%, 21% to 84%, and
      51% to 77%, respectively, for the three challenge doses. gpCMV antibody started
      after viral challenge increased pup survival after only the lowest challenge dose
      (51% to 81%). Antibody did not protect against CMV infection of the pups. CMV
      antibody appeared to improve survival in congenital CMV infection but did not
      affect vertical transmission.

PMID- 7561215
TI  - Intravitreous and plasma concentrations of ganciclovir and foscarnet after
      intravenous therapy in patients with AIDS and cytomegalovirus retinitis.
AB  - This study evaluated intravitreous and plasma ganciclovir and foscarnet
      concentrations after intravenous administration in AIDS patients with
      cytomegalovirus (CMV) retinitis and retinal detachment. Undiluted vitreous
      samples were prospectively obtained from 60 eyes (52 patients) at the time of
      pars plana vitrectomy. Thirty-three plasma samples (from 27 patients in the
      initial group of 52) were obtained simultaneously during surgery on 33 eyes. High
      pressure liquid chromatography showed the mean vitreous ganciclovir
      concentrations in patients on induction and maintenance therapy were,
      respectively, 4.74 +/- 1.49 microM (n = 24) and 3.29 +/- 1.84 microM (n = 30; P =
      .005). Simultaneous plasma ganciclovir concentrations were less than the vitreous
      concentrations in 78% of the patients. The mean intravitreous foscarnet
      concentrations in patients receiving induction dosages were 189 +/- 177 microM (n
      = 5) versus 163 +/- 167 microM (n = 4; P > .20) for those receiving maintenance
      therapy. The foscarnet vitreous plasma concentration ratio averaged 1.43. Current
      drugs and doses for CMV retinitis result in borderline or progressively
      subtherapeutic concentrations.

PMID- 7561216
TI  - Phenotypic and functional parameters of cellular immunity in a chimpanzee with a
      naturally acquired simian immunodeficiency virus infection.
AB  - The cellular immunologic and virologic status of a chimpanzee, naturally infected
      with a human immunodeficiency virus type 1 (HIV-1)-like lentivirus (SIVcpz-ant),
      was compared longitudinally with those of 3 HIV-1-infected and 5 uninfected
      chimpanzees for a period of 49 months. Evidence of immune deficiency was not
      observed in the HIV-1-infected chimpanzees, nor could virus be isolated from
      plasma. Virus could be isolated from plasma of the SIVcpz-ant-infected
      chimpanzee, but clinical signs of immune deficiency were never observed. Absolute
      CD4+ cell counts remained relatively stable, but NK cells fluctuated
      significantly over time and tended to correlate inversely with the virus titer in
      peripheral blood. Although only CD8+ T cells were directly demonstrated to exert
      a suppressive effect on viral replication in vitro, the observed fluctuation of
      NK cells suggests that these cells may also be involved in the interaction with
      lentivirus infection in this species.

PMID- 7561217
TI  - Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency
      virus (HIV) type 1 infection inhibit HIV-1 replication.
AB  - CD8 lymphocytes from asymptomatic human immunodeficiency virus (HIV) type 1
      infected patients can suppress virus production from infected CD4 cells.
      Suppressive activity is separate and distinct from cytotoxic T lymphocyte (CTL)
      reactivities and is likely mediated by a soluble factor(s). The majority of HIV-1
      suppression studies have been done in the context of bulk CD8 cell cultures. In
      this study, viral suppression was characterized by clonal populations of CD8
      cells derived from HIV-1-infected patients. Most of the suppressive clones were
      devoid of detectable CTL reactivity against env-, gag-, pol-, and nef-expressing
      targets. Among the suppressive clones derived from an individual patient, a
      marked heterogeneity was evident with respect to phenotypic markers, cytokine
      production, and T cell receptor V beta expression. These results suggest that
      noncytolytic virus suppression is oligoclonal in nature. Clones provide tools for
      future studies aimed at understanding the mechanism of suppression and
      identifying the suppressive factor.

PMID- 7561219
TI  - Characterization of Streptococcus pneumoniae from human immunodeficiency virus-
      seropositive patients with acute and recurrent pneumonia.
AB  - Thirty-two isolates of clinically significant Streptococcus pneumoniae from 11
      human immunodeficiency virus (HIV)-seropositive patients with single or multiple
      episodes of pneumonia were characterized by antibiotic susceptibility testing,
      serotyping, ribotyping, and repetitive extragenic palindromic polymerase chain
      reaction (REP-PCR). The isolates comprised 10 serotypes, 12 ribotyping patterns,
      and 12 REP-PCR patterns. There was close but not absolute correlation between
      techniques. By combining these characterization methods, 14 strains were
      identified. Five strains were found in > 1 patient, suggesting their frequent
      occurrence in this population. Two isolates of different serotype from 1 patient
      were highly related by ribotyping and REP-PCR, suggesting possible in vivo
      serotype change. Acute infection was associated with single strains or
      coinfection by distinct strains. Recurrent pneumonia was identified as relapse
      with the same strain or reinfection with new strains. The molecular
      characterization of pneumonococci from HIV-seropositive persons refines our
      understanding of pneumonococcal infection in these patients.

PMID- 7561218
TI  - High levels of human peripheral blood mononuclear cell engraftment and enhanced
      susceptibility to human immunodeficiency virus type 1 infection in NOD/LtSz
      scid/scid mice.
AB  - Inbred C.B-17-scid/scid mice accept human peripheral blood mononuclear cell
      (PBMC) xenografts and are susceptible to human immunodeficiency virus type 1 (HIV
      1) infection, but low levels of PBMC engraftment impede use of this system in HIV
      research. This report describes the effect of host strain background on human
      PBMC engraftment and HIV infectivity in scid mice. Back-crossing the scid
      mutation to the NOD/Lt strain (designated NOD/LtSz-scid/scid) increased the
      percentage of engrafted human PBMC in recipient spleens by 5- to 10-fold compared
      with that in C.B-17-scid/scid stock. Four weeks after human PBMC-injected mice
      were infected with HIV-1, 79% of NOD/LtSz-scid/scid spleens harbored replicating
      virus compared with only 39% of spleens in C.B-17-scid/scid mice. The NOD/LtSz
      scid/scid mouse may provide a useful small animal model for studies of HIV-1.

PMID- 7561220
TI  - Inhibition of toxic shock syndrome toxin-1-induced cytokine production and T cell
      activation by interleukin-10, interleukin-4, and dexamethasone.
AB  - Toxic shock syndrome toxin-1 (TSST-1) induced production of the cytokines tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6, IL-2, and interferon
      gamma (IFN-gamma) by human peripheral blood mononuclear cells (PBMC). In
      contrast, only low levels of IL-10 were present and IL-4 was absent in TSST-1
      stimulated PBMC. Addition of IL-10 to TSST-1-stimulated PBMC inhibited the
      production of TNF-alpha, IL-1, IL-6, and IFN-gamma by 68%, 93%, 70%, and 86%,
      respectively, but had less effect (14%-37%) on T cell proliferation. IL-4 was
      less effective than IL-10 in inhibiting cytokine production and had no effect on
      T cell proliferation induced by TSST-1. Dexamethasone, an antiinflammatory agent,
      was the most potent agent in controlling TSST-1-mediated effects, as evidenced by
      inhibited T cell proliferation (> 74%), reduced levels of cytokines (70%-84%),
      and reduced expression of CD25 and CD69 on PBMC. Thus, dexamethasone may be a
      useful agent to mitigate TSST-1-mediated toxic shock.

PMID- 7561222
TI  - Opioids and akathisia.

PMID- 7561221
TI  - Epidemiology and mortality risk of vancomycin-resistant enterococcal bloodstream
      infections.
AB  - Risk factors for vancomycin-resistant enterococcal (VRE) bloodstream infection
      (BSI) were studied at a tertiary-care hospital by comparing 46 patients with VRE
      BSI with 46 randomly selected patients with vancomycin-susceptible enterococcal
      (VSE) BSI. Among patients with an enterococcal BSI, risk factors for mortality
      were determined. Independent risk factors for VRE-BSI were increasing APACHE II
      score (odds ratio [OR], 2.3/5-point increase; 95% confidence interval [CI], 1.4
      3.9), receipt of vancomycin (OR, 11; 95% CI, 5.5-21), or diagnosis of hematologic
      malignancy (OR, 8.4; 95% CI, 3.9-18). After controlling for APACHE II score and
      gender, patients with VRE- versus VSE-BSI did not have a significantly elevated
      risk of mortality (OR, 3.3; 95% CI, 0.7-15). Five of 28 VRE blood isolates typed
      using pulsed-field gel electrophoresis had identical banding patterns. These data
      suggest that increasing severity of illness, underlying disease, and receipt of
      vancomycin are major risk factors for VRE-BSI.

PMID- 7561223
TI  - Control of cancer-related pain with MS Contin: a comparison between 12-hourly and
      8-hourly administration.
AB  - Nineteen cancer patients with chronic pain of moderate to severe intensity were
      randomized in a double-blind manner to 5 days of either 8-hourly or 12-hourly
      administration of controlled-release morphine (MS Contin, MSC), followed by the
      alternate schedule for 5 days. The control of pain, using an average dose of
      303.4 +/- 254.4 mg/day of MSC, was good during both the 8-hourly and 12-hourly
      phases, and the mean daily pain intensity measured by visual analogue scale
      (VAS), pain relief (VAS), and global efficacy scores did not differ when compared
      by treatment schedule. The need for supplemental "rescue" morphine was infrequent
      and did not differ between treatment phases (8-hourly, 0.7 +/- 0.7 and 12-hourly,
      0.6 +/- 0.6 doses per day, p = 0.6232). The overall frequency and severity of
      adverse events did not differ between the two dosing schedules. A majority of
      patients (67%) reported that they believed that 12-hourly dosing was a moderate
      or great advantage over 8-hourly dosing.

PMID- 7561224
TI  - Symptom distress in newly diagnosed ambulatory cancer patients and as a predictor
      of survival in lung cancer.
AB  - Levels of symptom distress are most often measured in a clinical trial context
      rather than in general ambulatory populations. The purpose of this paper is to
      report levels of symptom distress in such a population, and to describe the
      factors associated with this distress. Over a 6-month period, a consecutive
      sample of 434 newly diagnosed patients, including 82 patients with lung cancer,
      were tested with the symptom distress scale at two tertiary oncology clinics
      serving the population of one Canadian prairie province. While levels of symptom
      distress in this population were generally low, the most problematic symptoms for
      patients were fatigue and insomnia, with 40% and 30% having moderate or high
      scores on these symptoms, respectively. Patients with advanced disease reported
      more distress than those with early stage disease; women reported more distress
      than men; older patients had less distress than younger patients; distress was
      highest in lung cancer patients and lowest in men with genitourinary cancers.
      Consistent with the findings of four previous studies, the single measure of
      symptom distress was a significant predictor of survival in lung cancer patients,
      with the exception of three patients who had substantial post-thoracotomy
      symptoms.

PMID- 7561225
TI  - A survey of physician knowledge of drug costs.
AB  - Previous studies have indicated that physicians have inadequate knowledge of drug
      costs. This study was designed to determine actual pharmacy prices of 12
      nonsteroidal anti-inflammatory drugs (NSAIDs) and physicians' knowledge of these
      prices. Pharmacists (N = 67) in a large urban area were surveyed to determine the
      lowest retail price of commonly prescribed medications. Pain clinic and
      orthopedic physicians (N = 95) were surveyed to determine their knowledge of
      prices for 12 NSAIDs. There was wide variation between pharmacies in the cost of
      medications. Eighty-one percent of physicians agreed that cost is an important
      factor to consider. Only 25% of physicians estimated at least one-half of the
      medications between the highest and lowest pharmacy price. The results of this
      study indicate that physicians need more information about prices of medications
      they prescribe.

PMID- 7561226
TI  - What do nurses know and believe about patients with pain? Results of a hospital
      survey.
AB  - Nurses in every area of clinical practice are confronted with the challenge of
      caring for patients in pain. The purpose of this study was to determine nurses'
      knowledge and attitudes regarding pain in the acute and long-term care settings
      of a large Canadian teaching hospital. This paper reports the results of a pain
      survey completed by 514 nurses using the Nurses' Knowledge and Attitudes Survey
      (Ferrell and Leek, 1990). The mean percent score was 41. Nurses with a university
      education scored significantly higher (P < 0.0001) than those nurses who were not
      university prepared. Nurses who had attended educational sessions on pain
      management within the last year also scored significantly higher (P < 0.0001)
      than those who had not attended. Results indicated that nurses lacked knowledge
      and understanding of basic pain management principles, opioid usage, and acute
      and chronic pain. These results supported the value of advanced educational
      preparation and continuing education sessions for nurses, and the need and
      direction for pain management programs at this hospital.

PMID- 7561227
TI  - Pain, coping, and adjustment in patients with burns: preliminary findings from a
      prospective study.
AB  - We prospectively examined the associations between procedural pain during
      hospitalization and coping and adjustment 1 month postdischarge in 43 patients
      treated at a major regional burn center for burns extensive enough to require at
      least 5 days of daily wound debridement procedures. Both patients and nurses
      provided ratings of patient pain, which were summarized and aggregated across a 5
      day period. Results indicated that those subjects with higher pain scores also
      reported poorer adjustment as measured by scores on the Brief Symptoms Inventory
      and the Sickness Impact Profile. Moreover, these associations remained
      significant after partialling out the effects of preburn adjustment. Hierarchical
      regression analyses revealed evidence that seeking social support had a
      moderating effect on the association between pain and scores on a measure of
      posttraumatic stress disorder.

PMID- 7561228
TI  - A revised measure of acute pain in infants.
AB  - Acute pain in infants is not assessed or managed optimally. The objectives of the
      study were (a) to adapt a behavioral pain assessment measure (Children's Hospital
      of Eastern Ontario Pain Scale, CHEOPS) for use with infants, and (b) to establish
      the reliability and validity of the measure in a study of infants undergoing
      immunization. Ninety-six healthy 4- to 6-month-old infants were randomized to
      receive either the local anesthetic cream Eutectic Mixture of Local Anesthetics
      (EMLA) (N = 49), or a placebo (N = 47) prior to immunization. The infant's
      behavioral response was videotaped immediately before and following the
      immunization. Postprocedural pain scores were assessed from the videotape and
      were significantly lower in infants who received EMLA (P = 0.01). Pain scores
      were also significantly correlated with visual analogue scale (VAS) scores
      assessed during vaccination. Five independent raters also independently rated ten
      infants to determine interrater reliability. Agreement between raters' scores was
      high (intraclass correlation coefficient, 0.95). Results from this study suggest
      that this measure has beginning construct and concurrent validity and interrater
      reliability when used in a research study. Further testing of the measure in the
      clinical setting is required.

PMID- 7561229
TI  - Differential effects of hypnotic suggestion on multiple dimensions of pain.
AB  - Within the framework of multidimensional pain assessment, this study extended an
      earlier finding that hypnotic analgesia and relaxation suggestions have
      differential effects on pain reduction by evaluating these strategies in subjects
      undergoing a cold pressor protocol. Thirty-two highly susceptible subjects were
      randomly assigned to an analgesia or a relaxation suggestion treatment group. Six
      pain reports were taken at 10-sec intervals for each experimental condition. The
      baseline measures served as covariates. A 2 x 2 x 2 x 6 repeated-measures
      analysis of covariance (ANCOVA) revealed a significant group (analgesia,
      relaxation) by pain dimension (intensity, unpleasantness), by condition
      (suggestion alone, hypnotic induction plus suggestion) interaction. Analysis of
      the simple-simple main effects, holding both group and condition constant,
      revealed that application of hypnotic analgesia reduced report of pain intensity
      significantly more than report of pain unpleasantness. Conversely, hypnotic
      relaxation reduced pain unpleasantness more than intensity. The clinical
      implications of the study are discussed.

PMID- 7561231
TI  - Parenteral nutrition at home in advanced cancer patients.
AB  - There is controversy regarding the utility of parenteral nutrition in advanced
      cancer patients. In selected populations, such as those with digestive tract
      cancers, death may result from the absence of oral intake and not progression of
      disease. In some cases, patients and relatives request that artificial nutrition
      begun in the hospital continue after discharge. Clinical experience with the
      management of home parenteral nutrition in 13 cancer patients is described to
      highlight the ethical and technical problems that emerge during the treatment of
      such patients.

PMID- 7561230
TI  - Intravenous amitriptyline in pediatrics.
AB  - Oral amitriptyline has been used as an analgesic in a wide range of pain
      settings. Despite long-term availability of a parenteral form, the few reports
      about this formulation have been limited to pharmacokinetic studies in normal
      volunteers, trials in depressed patients, and analyses of electroencephalogram
      (EEG) activation. We retrospectively reviewed our experience using intravenous
      (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at
      Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate
      medications by the oral route, received IV amitriptyline for a variety of
      indications, including neuropathic pain, depression, sleep disturbance, and as an
      adjuvant agent for opioid analgesia. One patient experienced an extrapyramidal
      reaction temporally related to the administration of IV amitriptyline, which was
      successfully managed with diphenhydramine. Further prospective, controlled
      studies are needed to further assess the safety, efficacy and tolerability of
      this novel use of amitriptyline.

PMID- 7561232
TI  - Management of malignant ureteral obstruction in the palliative care setting.
AB  - Acute renal failure due to bilateral ureteral obstruction is a common problem in
      palliative care. We report on two patients with advanced rectosigmold carcinoma
      in which bilateral malignant ureteral obstruction was managed by pharmacological
      and endourologic methods, respectively. The first patient showed excellent
      response to high-dose corticosteroids. The second patient showed no evidence of
      response and a urinary diversion procedure was performed. Indications for both
      pharmacological and endourological interventions in these patients are discussed.
      Our findings suggest that decision regarding the management of ureteral
      obstruction needs to be highly personalized and follow careful discussion with
      the patient and/or family.

PMID- 7561233
TI  - Comparison of CA 72-4, CA 19-9 and CEA in the diagnosis and monitoring of gastric
      cancer.
AB  - In order to assess the utility of the tumor-associated antigen CA 72-4 in the
      diagnosis and monitoring of gastric cancer, this tumor marker was measured
      preoperatively in 718 patients. This group comprised 282 patients with malignant
      disease (115 with gastric cancer and 167 with other malignancies not involving
      the stomach) and 476 patients with benign surgical diseases. These results were
      compared with those for carcinoembryonic antigen (CEA) and the tumor-associated
      antigen CA 19-9. CA 72-4 was above the normal limit of 2.5 U/ml in 61% of the
      patients with gastric cancer, in 35% of the patients with other malignancies, and
      in 7% of the patients with benign diseases. CEA and CA 19-9 were elevated in 37%
      of the patients with gastric cancer ( > 3 ng/ml for CEA and > 37 U/ml for CA 19
      9). CA 72-4 levels were above 10 U/ml in 26% of the gastric cancer patients, in
      15% of patients with other malignancies, and in 0.4% of the patients with benign
      diseases. There was a good correlation between CA 72-4 level and tumor stage in
      gastric cancer. CA 72-4 serum levels were over 2.5 U/ml in 31%, 48%, 68% and 88%
      of patients with stage I, II, III and IV disease, respectively. CA 72-4 was found
      to be more sensitive than CEA and CA 19-9 in detecting recurrences of gastric
      cancer. In the postoperative-care period, carcinoma recurred in 29
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561234
TI  - Serum levels of procollagen type I carboxyterminal extension peptide in cancer
      patients with bone metastases.
AB  - Serum levels of procollagen type I carboxy-terminal extension peptide (PICP)
      reflect the synthesis of type I collagen. As PICP is produced by osteoblasts and
      is not incorporated into bone matrix, serum PICP levels have been suggested as a
      marker of bone formation. In 37 cancer patients (21 men and 16 women; age: 72.4
      +/- 8.6 (mean +/- SD) years) with bone metastases and 23 women (age: 77.3 +/-
      6.64 years) as controls, the following biochemical variables were measured: serum
      PICP, calcium (Ca), phosphorus, alkaline phosphatase (AP) and tartrate-resistant
      acid phosphatase (TRAP), and urinary hydroxyproline and calcium corrected for
      creatinine excretion. Higher serum levels of PICP were observed in cancer
      patients than in control (245 +/- 177 micrograms/l vs 121.7 +/- 36 micrograms/l,
      p < 0.01). Cancer patients also had higher AP levels than controls (704 +/- 755
      U/l vs 216.5 +/- 56 U/l, p < 0.01). Abnormal PICP and AP serum concentrations
      (above the mean + 2SD of controls) were found in 46% and 51% of patients,
      respectively. Moreover, patients showed significantly lower serum calcium
      concentrations (p < 0.001), and higher TRAP and hydroxyproline levels although
      statistical significance was not reached. In the patients, PICP was correlated
      directly with AP (r = 0.50, p < 0.01) and TRAP (r = 0.34, p < 0.05). In
      conclusion, patients with bone metastases have increased bone turnover as shown
      by serum markers. Serum PICP may be used as an adjunctive, non-invasive index to
      assess bone metabolism. However, the clinical usefulness of PICP in cancer
      patients needs further evaluations.

PMID- 7561235
TI  - Study of 2'5' oligo (A) synthetase in patients with metastatic renal cell
      carcinoma.

PMID- 7561236
TI  - Analysis of 2'5' oligo (A) synthetase in patients with advanced thyroid
      carcinoma.

PMID- 7561237
TI  - Influence of presurgical idiopathic hyperprolactinemia on relapse rate in
      operable breast cancer.

PMID- 7561239
TI  - Preliminary study on thymidine labelling index in human non-small cell lung
      cancer.

PMID- 7561238
TI  - Cytosolic tissue-type plasminogen activator (t-PA) levels in ductal infiltrating
      carcinomas of the breast classified according to different clinical and
      biological parameters.

PMID- 7561240
TI  - Zinc levels in serum during subcutaneous interleukin-2 immunotherapy of cancer.

PMID- 7561243
TI  - The clinical value of serum TPS in gynecological malignancies.
AB  - This study included 75 cases; 39 with gynecological cancer of different types,
      stages, and grades (14 ovarian, 11 endometrial, 9 cervical, and 5 vulvovaginal);
      23 patients with benign gynecological diseases and 13 normal healthy controls.
      Serum TPS was estimated using the ELISA kit supplied by Beki Diagnostic AB,
      Bromma, Sweden. The results of the present study revealed that serum TPS was
      significantly elevated in cancer patients followed by those with benign diseases.
      When the cutoff values were adjusted to 137 and 101 U/L, we obtained
      sensitivities of 56.4% and 82.1% at specifities of 100% and 85%, respectively.
      The benign diseases group had false positive rates of 13% and 34.8%,
      respectively. When considering tumor site, vulvo vaginal cancer showed the
      highest sensitivity (80%) followed by cervical (66.7%), ovarian (50%), and lastly
      endometrial cancer (45.5%). Serial measurement of TPS was shown to be of
      important value in the post-surgical follow-up of cancer patients.

PMID- 7561242
TI  - Serum soluble interleukin-2 receptors in epithelial ovarian cancer patients.
AB  - The levels of soluble interleukin-2 receptors (sIL-R2) were measured in the serum
      of 52 patients with epithelial ovarian carcinoma as well as in 25 age and sex
      matched normal controls. The mean serum level of sIL-R2 was increased in 37
      patients (71.2%). Comparison of these levels to those of normal controls showed a
      highly statistically significant difference (p < 0.001). Serum sIL-R2 levels were
      not related to histology, clinical stage or the presence of ascites (p = 0.58, p
      = 0.32 and p = 0.67, respectively), nor did they follow disease activity or
      response to chemotherapy. However, patients with higher pretreatment sIL-2R
      levels (more than 1200 U/ml) were found to have a longer survival (p < 0.02),
      possibly explained by the presence of activated lymphocytes and a better immune
      surveillance. We conclude that the serum level of sIL-R2: a) is elevated in
      ovarian cancer patients, b) has no relationship with histological subtypes, tumor
      burden or the presence of ascites, c) cannot serve as a valuable tumor marker for
      the monitoring of patient treatment, and d) has a prognostic value for survival.

PMID- 7561241
TI  - Analysis of antiglobulin (HAMA) response in a group of patients with B
      lymphocytic malignancies treated with 131I-Lym-1.
AB  - Host development of human anti-mouse antibodies (HAMA) in response to
      administered antibodies has been reported as a problem for antibody imaging and
      therapy. However, radioimmunotherapy has been shown to be effective in patients
      with B-cell malignancies because their immunodeficient state precludes or delays
      development of a HAMA response to mouse antibodies. Baseline HAMA activity was
      assayed in 60 patients with B-lymphocytic non-Hodgkin's lymphoma or chronic
      lymphocytic leukemia and sequentially in 43 patients who were subsequently
      treated with radiolabeled Lym-1 antibody. Pre-existing "HAMA" activity was found
      in 3 (5%) of the 60 patients screened for treatment consideration. The incidence
      of development of HAMA in the 43 patients treated with multiple doses of
      radiolabeled Lym-1 antibody was 12 (28%). There was no evidence for an
      anaphylactoid or related response in the HAMA positive patients. HAMA activity
      interrupted therapy in 14% of the patients (6 of 43) but did not preclude
      therapeutic responses to radiolabeled Lym-1 therapy. Medial survival for the HAMA
      positive patients was longer (18 months) than for those who did not develop HAMA
      activity (9 months).

PMID- 7561246
TI  - [The role of IL-10 in patients with SIRS (systemic inflammatory response
      syndrome)--in relation to TNF activity].
AB  - The role of IL-10 (Interleukin 10) in the patients with SIRS was demonstrated in
      relation to the TNF (Tumor Necrosis Factor). 1. Clinical observations Thirty
      three materials of IL-10 and 43 materials of TNF were taken from a total of 46
      patients with SIRS. And their concentration of serum were compared with those of
      healthy volunteers (TNF: n = 12, IL-10: n = 9). The value of IL-10 and TNF in
      SIRS patients was significantly higher than those of healthy volunteers (p > 0.05
      in IL-10, p < 0.01 in TNF). Also, the values of both IL-10 and TNF in the
      patients with MOF (n = 22) were higher than those of the patients without MOF (n
      = 24) (p < 0.05 in IL-10, p < 0.01 in TNF). Both the serum values of IL-10 and
      TNF in 7 patients with SIRS, whose materials were obtained at two points of their
      clinical course, were decreased in accordance with the favorable prognosis. In
      these patients, the changes in IL-10 and TNF were observed in parallel. 2.
      Experimental observations Five 4 week ICR mice were used in an experimental
      study. The serum concentration of TNF and IL-10 increased to the maximum at 2
      hours after 4 mg/kg of LPS injection. TNF level disappeared at 6 hours, but IL-10
      level still remained at this point. Both the serum and BALF levels of TNF
      increased by LPS injection which was inhibited by the intraabdominal pretreatment
      of 200 micrograms of IL-10 (in serum: p < 0.1, in BALF: p < 0.05). By
      preincubation of mice alveolar macrophages with IL-10, TNF production from the
      macrophage resulting from LPS loading also was significantly inhibited (p <
      0.01). 3. From the above, it may be concluded that IL-10 inhibits TNF secretion
      from monocyte and protects against the pathogenic activity of TNF in the SIRS
      patient.

PMID- 7561244
TI  - Correlation between pS2 protein positivity, steroid receptor status and other
      prognostic factors in breast cancer.
AB  - The cytosolic levels of pS2, an estrogen-regulated protein, were measured in 100
      cases of primary breast cancer and related to several conventional histological
      and biochemical prognostic factors. The data were statistically analyzed on the
      basis of two different cutoff point for pS2: 4 and 11 ng/mg of cytosolic
      proteins. pS2 positivity (cutoff 11 ng/mg) was shown to be associated with small
      tumor size (p = 0.05), a higher differentiation grade (p = 0.007) and a smaller
      number of mitoses (p = 0.004), but not with menopausal status, lymph node
      involvement, cathepsin D levels, or proliferative activity determined by the
      monoclonal antibody Ki67. With the cutoff of 4 ng/mg, the statistical
      significance was confirmed only for the number of mitoses (p = 0.03), which was
      also the most closely related covariate in multivariate analysis (p = 0.008). As
      regards steroid receptor status, a significant difference was observed between
      pS2+ and pS2- cases (Chi-square = 8.9; p = 0.04, cutoff 4 ng/mg). in conclusion,
      pS2 positivity, being preferentially expressed in hormone-dependent cells and
      related to other well-known positive markers, may either indicate a good
      prognosis or predict responsiveness to endocrine treatment.

PMID- 7561245
TI  - CA 549 and SP2 in postoperative breast cancer patients. Comparison with CA 15.3,
      CEA and TPA.
AB  - The levels of CA 549 and SP2 were measured in 430 subjects: 100 healthy blood
      donors, 130 patients with benign diseases and 200 postoperative breast cancer
      patients. In the latter group, the serum levels of CA 15.3, CEA and TPA were also
      measured. The Kolmogorov-Smirnov, Mann Whitney and McNemar tests were used for
      statistical analysis. The upper normal limits were established on the basis of
      the values obtained in the healthy blood donors group, the benign diseases group
      and R.O.C. analysis of the breast cancer group. They were: CA 549 = 13 U/ml, SP2
      = 14 U/ml, CA 15.3 = 35 U/ml, CEA = 5 ng/ml and TPA = 110 U/ml. The sensitivity,
      specificity and accuracy in the breast cancer group were, respectively: CA 549 =
      78.1%, 97.1% and 88%; SP2 = 21.9%, 90.4% and 57.5%; CEA = 66.7%, 95.2% and 81.5%;
      CA 15.3% = 80.2%, 98.1% and 89.5%, and TPA = 73.9%, 78.8% and 76.5%. Statistical
      analysis showed significant differences only between CA 15.3, the marker which
      gave the best results, and SP2 (p < 0.001). There was no significant differences
      with the association of two or three tumor markers.

PMID- 7561247
TI  - [Experimental infection of infant rabbits with verocytotoxin-producing
      Escherichia coli of bovine origin].
AB  - Infant rabbits were used as a model to study the diarrhogenicity of verocytotoxin
      producing Escherichia coli (VTEC) isolated from bovine. Infant rabbits aged 6
      days were inoculated intragastrically with 10(9) viable bacteria of four VTEC or
      three non-VTEC strains. Of these strains, three strains (VT+, eaeA+), one strain
      (VT+, eaeA-) and one strain (VT-, eaeA+) caused diarrhea in rabbits 48 to 60 hr
      after inoculation. None of the two strains (VT-, eaeA-) caused symptoms. Based on
      these results, it is suggested that the 6-day-old infant rabbit is a suitable
      animal for studying diarrhea caused by VTEC or eaeA-positive E. coli strains of
      bovine origin.

PMID- 7561249
TI  - [Type-specificity of serum antibodies from genital herpes patients as determined
      by an enzyme-linked immunosorbent assay using HSV-infected cells as antigens].
AB  - Type-specificity of serum antibodies from genital herpes patients was determined
      by an enzyme-linked immunosorbent assay (ELISA) using antigens extracted from
      herpes simplex virus (HSV) type 1- and 2-infected cells. Sixty-three of HSV type
      known panel sera, which had been typed by HSV glycoprotein G-specific immunodot
      analysis, consisted of 3 groups; group I (25 sera; gG-1 antibody- and HSV-1
      isolation-positive), group II (19 sera; gG-2 antibody- and HSV-2 isolation
      positive) and group III (19 sera; gG-1 and gG-2 antibodies- and HSV-2 isolation
      positive), were assayed for IgM, IgA, IgG1 and IgG3 antibody activities (optical
      densities) against HSV-1- as well as HSV-2-infected cell antigens. IgG antibodies
      of these 3 groups showed 2 different patterns of reactivities. The group II sera
      reacted with the two antigens to the same extent and could be differentiated from
      other 2 groups. The latter 2 groups were difficult to differentiate because of
      similar reaction patterns showing higher reactivities to HSV-1 antigen. In
      contrast, type-specificity was not observed in IgM antibody activities. The
      higher reactivities of IgG antibody to HSV-1 antigen than to HSV-2 antigen in the
      group III sera indicate the "original antigenic sin" phenomenon, i.e.; memory B
      cells produced in prior infection with HSV-1 were activated by cross-reactive
      antigens of HSV-2 which infected secondarily. To presume the type of infected HSV
      from serum antibody reactivities was difficult as long as HSV-infected cells were
      used as antigens in ELISA.

PMID- 7561248
TI  - [Haemophilus aphrophilus isolated from the blood of a patient with infective
      endocarditis].
AB  - On July 1994, a 62-year-old female, having a history of mitral regurgitation, was
      admitted because of high fever, hematuria and conjunctival petechiae. She was
      diagnosed as having infective endocarditis with mitral valve vegetation proved by
      ultrasonic cardiography. The gram negative rods were isolated from blood cultures
      performed five times, performed prior to the administration of antibiotics. The
      isolates were identified as strains of H. aphrophilus. After two days of
      treatment with PCG (12 million units/day), the organism became undetectable from
      the blood. Since the minimal inhibitory concentrations (MICs) of PCG and ABPC
      were ranged between 0.06-2.0 micrograms/ml and 0.06-0.5 microgram/ml,
      respectively, ABPC was selected as a first choice antibiotic instead of PCG. ABPC
      was given 12 g/day for the first 3 days, then 6 g/day for 28 days, followed by 3
      g/day for 7 days. The patient recovered and was discharged after the 55 hospital
      days. H. aphrophilus grew on BTB lactose agar, chocolate agar and sheep blood
      agar, but failed to grow on MacConkey agar. H. aphrophilus produced smooth
      transparent nonhaemolytic micro colonies after 48 hours on sheep blood agar and
      chocolate agar plates. Atmosphere with 5% CO2 failed to enhance their growth. All
      the five strains of H. aphrophilus isolated, required neither factors V nor X.
      Positive synthesis of porphyrin from delta-aminolevlinic acid confirmed their
      ability to grow without X factor. For the correct identification of H.
      aphrophilus strains, fermentation test of glucose, lactose, maltose and sucrose
      in either phenol red broth or CTA medium are necessary.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7561250
TI  - [A nation-wide surveillance of pathogen in elderly patients with urinary tract
      infections. 1st Report: Distribution of pathogen].
AB  - A nation-wide surveillance of causative organisms was conducted on 1,699 elderly
      patients with UTIs aged more than 65 in 190 private clinics and 73 hospitals in
      August and September, 1993, in order to investigate the distribution of causative
      bacteria and the relationship between isolates and the background of those
      patients. From 1,233 of the 1699 patients, 1,636 strains were isolated. E. coli
      was isolated most frequently (30%). in male and older patients, less E. coli were
      isolated, while more attenuated Gram negative rods such as NFGNR including P.
      aeruginosa were found. A similar trend was observed in uncomplicated UTIs
      isolates in this study. More E. coli were isolated from patients with stronger
      subjective symptoms while more bacteria other than E. coli were isolated in those
      with weaker subjective symptoms. From the above findings, it was confirmed that a
      high recovery rate of opportunistic pathogen which is less susceptible to various
      antibacterials is one the refractory factors in elderly patients with UTIs.
      Therefore, it is necessary to select a suitable antibacterial that can be used
      for complicated UTIs in elderly patients even when diagnosed as uncomplicated
      UTIs. Regardless of the size of the clinic or hospital, when treating elderly
      patients, with unsatisfactory results in initial treatment and with less
      subjective symptoms the physician must bear this in mind.

PMID- 7561251
TI  - [A nation-wide surveillance of pathogen in elderly patients with urinary tract
      infections. 2nd Report: Sensitivities of pathogen for oral antibacterial agents].
AB  - A nation-wide surveillance of sensitivities of bacteria, which were isolated from
      elderly patients with UTIs aged more than 65 in 190 private clinics and 73
      hospitals, for oral antibacterials, CPFX, OFLX, NFLX, CPDX and CCL, was conducted
      in August and September in 1993. Antibacterial activities of 5 agents against all
      1,511 strains were intensified in CPFX, OFLX, NFLX, CPDX and CCL in that order.
      Major pathogens such as Enterobacteriaceae, E. faecalis, Staphylococcus spp. and
      P. aeruginosa were more susceptible to fluoroquinolones than cephems. The rate of
      resistant strains to antibacterials was higher in isolates from older patients,
      patients with complicated UTIs and with indwelling catheter. The representative
      of resistant strains was P. aeruginosa, and about 50% of the strains of P.
      aeruginosa were resistant to even CPFX which had the most superior antibacterial
      activity among the 5 agents. About 40% of the S. aureus were MRSA, which were
      almost resistant to the 5 agents. From the above findings, it was confirmed that
      a high recovery rate of strains which is less susceptible to various
      antibacterials is one of the refractory factors in elderly patients with UTIs,
      particularly in complicated UTIs and with indwelling catheter. Regardless of the
      size of the clinic or hospital, Fluoroquinolones are more suitable for the
      treatment of elderly patients with UTIs than cephems.

PMID- 7561252
TI  - [Heterogeneity of lipopolysaccharide chain size of Pseudomonas aeruginosa
      isolated from different clinical sources--with reference to gentamicin
      susceptibility and serotype].
AB  - Lipopolysaccharide (LPS) compositions of P. aeruginosa isolated from from
      clinical sources such as blood, urine, pus, sputum, and feces were analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and
      aminoglycoside-susceptibility and serotype of these isolates were investigated in
      this study. Fifty-nine isolates tested were divided into three groups according
      to the difference in their LPS compositions; 35 strains with the long-LPS chain
      (B-band LPS), 14 strains with the short chain (A-band LPS) and 10 LPS-deficient
      strains. The relationship between the LPS compositions and their sources of 59
      strains were investigated. The majority of clinical isolates (12 of the 13
      strains) from the blood samples possessed the long-LPS chain (B-band LPS) and the
      remaining possessed the short-LPS chain (A-band LPS). About 67% each of the
      isolates from urine and feces possessed the long-LPS chain, and the minor part of
      both groups possessed the short-LPS chain. In isolates from both sputum and pus
      samples, the long- and short-LPS chains were found at almost the same rate, and
      the LPS-deficient isolates were found in the sputum samples at a considerably
      high rate of 42%. The 19 of the 35 isolates with the long-LPS chain were
      susceptible to gentamicin (54%) and 12 isolates were resistant (34%). On the
      other hand, the 14 isolates with the short chain were divided roughly into three
      groups, gentamicin-resistant, and -susceptible groups and intermediate groups. It
      was also notable that 7 of the 10 LPS-deficient isolates were resistant to
      gentamicin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561253
TI  - [A trial of clinical application of sparfloxacin for treating mycobacterial
      infections].
AB  - Sparfloxacin seems to be a good candidate for antimycobacterial treatment.
      However, there have been no clinical studies. We experienced 2 SPFX-treated
      cases, who could not use other antimycobacterial agents because of side effect,
      we tried SPFX-treatment on these cases. Good results were obtained, however, for
      long time use to prevent side effects, we tried SPFX every second day and
      monitored the serum levels of SPFX. SPFX-every second day treatment gave good
      clinical results and adequate serum levels of SPFX were observed.

PMID- 7561254
TI  - Rapid detection of Vibrio cholerae with a new selective enrichment medium and
      polymerase chain reaction.
AB  - The inhibitory effect of metallic EDTA compounds on growth of Vibrio cholerae and
      Escherichia coli was studied. Only Fe-EDTA among the compounds tested showed pH
      dependent growth inhibition on E. coli at pH 9.0, but no inhibition of V.
      cholerae at the same pH. By addition of Fe-EDTA as a selective inhibitor, a novel
      enrichment broth (tentatively designated as VCF broth) for the selective
      isolation and cultivation of V. cholerae from other Gram-negative bacilli has
      been developed, and the selective enrichment capacity of VCF broth for V.
      cholerae and selective inhibiting activity against E. coli were significantly
      higher than those of alkaline peptone water. A simple procedure for rapid
      detection of V. cholerae by selective enrichment for 6 hr with VCF broth and then
      amplification of the cholera toxin target DNA fragment by the polymerase chain
      reaction was presented. VCF broth may be a useful tool for the selective
      enrichment of V. cholerae in bacterial examinations.

PMID- 7561255
TI  - [A case of myelodysplastic syndrome who died of septic pulmonary embolism].
AB  - A case of myelodysplastic syndrome (MDS) complicated by septic pulmonary embolism
      is reported. A 61-year-old female who had been followed for refractory anemia
      with excess of blasts suddenly died of acute respiratory failure. An autopsy
      revealed massive pulmonary emboli with gram-positive cocci gathered in the emboli
      and alveolar spaces. Staphylococcus aureus was also detected through a blood
      culture from the right atrium. We speculate that pulmonary embolism was the
      result of septicemia induced by the immunosuppressive condition associated with
      MDS.

PMID- 7561256
TI  - [A case of tsutsugamushi disease which occurred in south western Shikoku].
AB  - We report a case of tsutsugamushi disease found in south western Shikoku. A 64
      year-old male who lived in Towa Village in Kochi, developed a fever and headache
      on April 6, 1994, and was admitted to Uwajima City Hospital on April 15, with a
      ten-day history of illness. He had an eschar on the right anterior side of the
      breast and an enlargement of the right axillary lymph node, without a rash.
      Laboratory data showed mild liver injury and atypical lymphocytes with 6% in
      peripheral blood. After his blood was drawn for rickettsial isolation, the
      minocycline was administered. His symptoms improved rapidly and was discharged in
      good condition. We successfully isolated the causative agent, Rickettsia
      tsutugamushi, and designated it as the Shiba strain. High antibody titer against
      the Kato, Karp and Gilliam strains was detected in serum on admission and
      increased during the course of the disease. In Shikoku, tsutsugamushi disease is
      rare and only 13 cases were reported during last ten years. Especially in south
      western district of Shikoku, there have been no case reported since 1960. This
      case is important epidemiologically and suggests that we should pay attention to
      this disease.

PMID- 7561257
TI  - Promising new carbapenem antibiotics for treatment of neonatal meningitis due to
      Campylobacter fetus.

PMID- 7561258
TI  - [Growth inhibition effect of amino acids on obligate oligotrophs isolated from
      clinical materials].

PMID- 7561259
TI  - Snake oil or miracle?

PMID- 7561260
TI  - Thrombolytic therapy for brain attack.
AB  - Stroke, otherwise referred to as "brain attack," remains one of the most
      devastating diseases in the country today. Each year, approximately half a
      million strokes occur and approximately 150,000 stroke victims survive. According
      to the American Heart Association, it is considered the leading cause of
      permanent disability in adults. The need to view strokes as a medical emergency
      is imperative to improve the outcomes of stroke. Current therapies are marginally
      effective. However, clinical trials at many institutions are in progress, with
      the goal of improving current therapy and patient outcomes. Thrombolytic therapy
      has recently been shown to be beneficial in acute ischemic stroke. Recent
      advances in endovascular techniques, improvements in catheters allowing the
      delivery of intra-arterial thrombolytic therapy, and the availability of
      screening procedures such as computed tomography (CT) scanning and angiography
      have given researchers and healthcare institutions the impetus to develop a
      protocol to improve outcome. Education and collaboration among all disciplines of
      health care professionals are essential in this endeavor.

PMID- 7561261
TI  - Cognitive status as a predictor of right hemisphere stroke outcomes.
AB  - The care of stroke patients continues to present a challenge to health care
      professionals. There is evidence that the quality of life following a stroke is
      related to functional status and also emotional, behavioral and cognitive
      abilities. The purpose of this study was to examine the relationship between
      emotional, behavioral and cognitive status and functional activity status of
      stroke survivors. The sample of 15 right hemisphere stroke patients was seen at
      four time periods after the stroke and they were assessed using the
      Neurobehavioral Rating Scale (NRS) and the Barthel Functional Index (BFI). The
      most frequently occurring mental status changes at six months were somatic
      concern, memory deficit, depressive mood and mental fatigue. There was a
      correlation between cognitive ability and functional ability. Although there was
      improvement over time in the scores of the NRS and BFI, there remained sufficient
      cognitive impairment to affect functional ability. Findings indicated the need
      for nurses to assess mental status when planning rehabilitation to establish
      realistic goals. Further research is needed with larger samples to examine the
      effects of stroke outcomes on functional ability.

PMID- 7561262
TI  - Intrathecal baclofen for spasticity of cerebral palsy: project coordination and
      nursing care.
AB  - Spasticity caused by cerebral palsy is painful and disabling. Infusion of an
      intrathecal antispasmodic for relief is investigated in a multicenter,
      interdisciplinary clinical trial. Clinical nurse specialists coordinate local
      team endeavors. The nursing process serves as a functional framework for project
      development, protocol implementation and long-term patient follow-up.

PMID- 7561263
TI  - Continuous bedside cerebral blood flow monitoring.
AB  - Continuous cerebral blood flow monitors are being used in critically ill
      neuroscience patients to assess blood flow in vulnerable regions of the brain and
      to evaluate the effects of treatments on these areas. Neuroscience nurses need to
      interpret cerebral blood flow values in relation to the many other physiologic
      parameters which are monitored in this population. Case studies are used to
      illustrate various patterns of regional blood flow in response to brain insults
      and therapeutics. Research implications of continuous cerebral blood flow
      monitoring are explored.

PMID- 7561264
TI  - Hyperbaric oxygen therapy for rhinocerebral fungal infection.
AB  - Rhinocerebral mucormycosis is an acutely fatal fungal infection that usually
      arises in the ethmoid sinuses, spreads into the orbits and then into the cranial
      cavity. It is typically seen in diabetic or immunocompromised patients. Therapy
      includes aggressive surgical debridement, administration of high-dose
      amphotericin-B and control of underlying predisposing conditions. Adjunctive
      hyperbaric oxygen (HBO) is another treatment modality that appears to be
      promising; oxygen in sufficient concentrations is fungicidal and decreases
      acidosis thereby increasing tissue survival. It is important for the neuroscience
      nurse to have an understanding of this deadly infection and the role in preparing
      the patient for HBO therapy to better plan care.

PMID- 7561265
TI  - Preparatory information for myelogram.
AB  - This study identified preparatory information appropriate for patients undergoing
      myelogram. Twenty-eight patients (16 lumbar and 12 cervical) described the
      sensations they experienced as they were having a myelogram. Sensations reported
      by 40% or more of the participants having both kinds of myelograms included hard,
      cold examining table; wet and cold cleansing of site; stick with injection of
      local anesthetic; sharp stick with spinal needle insertion; and burning
      (cervical) or sharp, tingling (lumbar) with contrast medium injection. These
      sensations, linked with the temporal elements of the procedure, yield a
      preparatory information intervention appropriate for those scheduled for
      myelogram. When preparatory information is used for the same myelogram procedure
      as described in this study, patients should experience reduced anxiety before and
      during the procedure.

PMID- 7561266
TI  - Overview of the data collection process.
AB  - The data collection plan is a series of well-thought-out strategies to implement
      the data collection process. The details of the plan are written out on paper.
      Once the research proposal is approved the data collection plan is implemented.
      This implementation is the action or doing phase of the study. The aim of this
      phase is to collect the evidence or data. During implementation, the researcher
      can experience problems related to people, researcher, institution and events.
      The data collection process is a time that is very challenging and requires the
      researcher to use mental and interpersonal skills.

PMID- 7561267
TI  - Orientation and preceptorship: the new research clinician's lifeline.
AB  - To develop a quality program is a long process. One must understand the program
      to develop it. Administrative support is vital to a successful program. The
      practical collaborative approach to helping the new employee integrate into the
      work environment efficiently and effectively is a reward for both the preceptee,
      preceptor, manager and employer.

PMID- 7561269
TI  - [The effectiveness of preoperative steroid therapy in preventing postoperative
      circulatory system complications in surgery of esophageal cancer].

PMID- 7561270
TI  - [Perioperative management of esophageal cancer--correlation between postoperative
      complication and oxygen consumption].

PMID- 7561268
TI  - [Functional recovery and preservation in view of reconstruction in respiratory
      tract surgery].

PMID- 7561271
TI  - [Perioperative metabolism and its management in esophageal cancer].

PMID- 7561272
TI  - [Perioperative management in esophageal cancer. Timing for starting postoperative
      enteral nutrition].

PMID- 7561274
TI  - [Basic and clinical studies on the prevention of postoperative MRSA infections in
      esophageal cancer].

PMID- 7561273
TI  - [Total intravenous anesthesia and postoperative continuous epidural infusion in
      thoracic esophageal cancer surgery].

PMID- 7561278
TI  - [Long term result and prognostic factors of stage I lung cancer after resection.
      Combined analysis of the biological malignancy potential].

PMID- 7561275
TI  - [Prognostic factors of stage I lung cancer after resection].

PMID- 7561276
TI  - [Prognostic factors of stage I lung cancer and oncogenes].

PMID- 7561277
TI  - [The proliferative ability of stage I lung adenocarcinoma and the correlation
      between host immunity and prognosis].

PMID- 7561279
TI  - [Stage I lung cancer patients who died from early relapses].

PMID- 7561280
TI  - [Surgical results of stage I lung cancer. Pleural lavage cytology, tumor markers,
      and gene analysis].

PMID- 7561281
TI  - [Is prospective histocompatibility testing necessary?].

PMID- 7561282
TI  - [Heart preservation and long-term function and growth of the transplanted heart].

PMID- 7561283
TI  - [Pulmonary lobe transplantation in pulmonary hypertensive dogs under
      cardiopulmonary bypass].

PMID- 7561284
TI  - [Experimental study on the production of endothelial-derived relaxing factor
      after pulmonary ischemia reperfusion injury].

PMID- 7561286
TI  - [Clinical and experimental studies on the causes of chronic coronary
      arteriosclerosis after heart transplantation].

PMID- 7561285
TI  - [Experimental and clinical studies on the effectiveness of new immunosuppressive
      agents used in heart transplantation and transplantation-related complications].

PMID- 7561287
TI  - [The long-term result of coronary bypass surgery in the past 19 years].

PMID- 7561288
TI  - [The long-term result of 1,728 cases of coronary bypass surgery. A multivariate
      analysis].

PMID- 7561289
TI  - [The long-term result of coronary bypass surgery. Prognosis of internal thoracic
      artery bypass to the left anterior descending coronary artery].

PMID- 7561290
TI  - [Long-term result of 1,000 cases of coronary artery bypass surgery].

PMID- 7561291
TI  - [Long-term result of coronary artery bypass surgery ten years after the surgery].

PMID- 7561292
TI  - [Valvuloplasty for mitral valve prolapse].

PMID- 7561293
TI  - [Mitral valve valvuloplasty using sliding plasty].

PMID- 7561295
TI  - [Mitral valve valvuloplasty for congenital mitral valve regurgitation].

PMID- 7561297
TI  - [Different techniques in aortic valve valvuloplasty].

PMID- 7561294
TI  - [Difficult cases in mitral valve valvuloplasty, intraoperative evaluation and
      surgical techniques].

PMID- 7561296
TI  - [Complete endocardial defect with atrioventricular valve reconstruction.
      Annuloplasty and ventricular septal defect closure with small patch].

PMID- 7561299
TI  - [Combined resection and reconstruction of the right heart].

PMID- 7561300
TI  - [Pulmonary artery reconstruction in lung cancer surgery with functional
      preservation].

PMID- 7561301
TI  - [Revascularization using vascular prosthesis in respiratory tract surgery].

PMID- 7561298
TI  - [Mediastinal malignant tumor resection and superior vena cava revascularization.
      Resection of invasive thymoma with growth into the superior vena cava and right
      atrium using cardiopulmonary bypass].

PMID- 7561303
TI  - [Surgical treatment for Pancoast tumor of the lung].

PMID- 7561302
TI  - [Revascularization in lung cancer surgery. Reconstruction of the low pressure
      blood vessels].

PMID- 7561304
TI  - [Simultaneous carotid endarterectomy and open heart surgery].

PMID- 7561305
TI  - [Strategies for treating cerebrovascular complications in CABG patients].

PMID- 7561306
TI  - [The effectiveness of cerebrovascular complication prevention in single clamp
      coronary artery bypass surgery and non-clamping selective cerebral perfusion
      thoracic aorta aneurysm surgery].

PMID- 7561308
TI  - [Selective cerebral perfusion during the surgery of thoracic aortic aneurysms in
      139 cases].

PMID- 7561307
TI  - [Experimental study on brain phosphorus energy metabolism during retrograde
      cerebral perfusion using 31-P magnetic resonance spectroscopy].

PMID- 7561309
TI  - [Incidence and prevention of cerebrovascular complications in thoracic aortic
      aneurysm surgery].

PMID- 7561310
TI  - [Open heart surgery with bloodless priming for ventricular septal defect and
      pulmonary hypertension].
AB  - In 17 patients with ventricular septal defect and pulmonary hypertension (VSD,
      PH) weighing 5.2 kg to 9.5 kg, open heart surgery was conducted with bloodless
      priming (total priming volume: 370-470 ml). None of the patients required blood
      transfusion during their hospital stay. The post-operative respiratory status was
      excellent in all cases with duration of intubation being 6 +/- 3 hours. While 12
      patients weighing over 6.6 kg maintained individual constant hematocrit (Hct)
      values during cardiopulmonary bypass (CPB), all 5 patients weighing under 6.1 kg
      showed significant decrease during rewarming (17 +/- 2% after initiation of CPB
      to 14 +/- 2% during rewarming). The lowest Hct value was 12% during rewarming in
      6.0 kg infant. The pre-operative circulating blood volume (CBV) was calculated
      retrospectively from the priming volume, the Hct value after anesthetic induction
      and the Hct value after initiation of CPB. The relationship, CBV (ml) = body
      weight (kg) x 72-13 (r = 0.85, p < 0.01) was derived. Using this equation, we
      calculated the predicted Hct level after initiation of CPB using the 370 ml
      bypass circuit in 43 VSD PH patients weighing 3.4 kg-5.9 kg. The Hct values were
      17 +/- 2% in 13 patients weighing over 5 kg with 12 (91 percent) above 15%, and
      13 +/- 2% in 30 patients weighing under 4 kg with 3 (11 percent) above 15%. Hct
      levels of 34%-36% before CPB were essential in patients weighing 4.0 kg-4.9 kg
      for the Hct level after initiation of CPB to exceed 15%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7561311
TI  - [Surgery of aneurysm of the left subclavian artery applying imaged thoracoscopy-
      a case report].
AB  - A 23-year-old male with aneurysm of the left subclabian artery was successfully
      treated by means of imaged thoracoscopic surgery. The operation was carried out
      using double-lumen endotracheal anesthesia. Short trocars were inserted through
      the left intercostal spaces to introduce a flexible video thoracoscope and
      surgical instruments. After the area around the proximal end of the subclabian
      artery was exposed, a tape and Nelaton tube were applied in order to interrupt
      the artery completely. The maneuvors for aneurysm could be accomplished with
      minimum invasion, and without thoracotomy. The advantages of this thoracoscopic
      surgery are: less postoperative pain and discomfort, early recovery and short
      hospital stay, and cosmetic preservation.

PMID- 7561312
TI  - [Resection of the posterior mediastinal gastric tube used in reconstruction after
      radical surgery for esophageal cancer--case reports].
AB  - Two patients are presented who underwent resection of a gastric tube placed in
      the posterior mediastinum during reconstruction following radical esophageal
      resection for esophageal cancer. The indications for gastric tube resection were
      bleeding from a peptic ulcer in one and gastric cancer in the other. Case 1: A 72
      year-old man, who had undergone a thoracic esophagectomy 3.5 years prior to
      admission, presented with a chief complaint of hematemesis. The gastric tube was
      resected and replaced with an antethoracic, pedicled segment of left colon.
      Pathologic examination of the resected gastric tube revealed a penetrating peptic
      ulcer. Case 2: A 65-year-old man with esophageal cancer and early gastric cancer
      underwent thoracic esophagectomy with combined resection of the fundus and lesser
      curvature of the stomach. One year later, he was found to have a new early
      gastric cancer in the antrum. The distal portion of the gastric tube was resected
      and replaced with a pedicled jejunal graft. Of the 526 patients with esophageal
      cancer treated in our department from 1972 to 1993, peptic ulcers were evident in
      the gastric tube used to reconstruct the esophagus in only seven cases. The
      stomach was resected in only one of these patients. Similar patients requiring
      gastric tube resection have been reported. All six of these cases are reviewed.
      Cancer of the gastric tube developed in 3 of the 526 patients. Although 74 cases
      of gastric tube cancer have been reported in the Japanese literature, the patient
      presented here (case 2) is the first to undergo successful resection of the
      stomach from the posterior mediastinal position.

PMID- 7561313
TI  - [A case of visceral ischemia associated with acute type IIIb aortic dissection].
AB  - The case was a 61-year-old man who was transported to our hospital with
      complaining of severe chest and back pain of sudden onset and diagnosed as acute
      type IIIb aortic dissection. Inspite of intensive medical treatments, severe
      abdominal pain with abdominal distension and progressive metabolic acidosis
      appeared at around 11 hours after admission. Aortogram revealed obstruction of
      both superior and inferior mesenteric arteries suggesting visceral ischemia
      associated with acute type IIIb aortic dissection. Emergent operation consisting
      of bypass grafting for the superior and the inferior mesenteric arteries with
      saphenous vein, partial resection of small intestine, left hemicolectomy and
      construction of artificial anus was immediately carried out. The patient had no
      particular trouble after the operation and returned to the previous job.

PMID- 7561314
TI  - [Two cases underwent patch closure and mitral annuloplasty for ventricular septal
      perforation and mitral regurgitation caused by acute inferior myocardial
      infarction].
AB  - Two cases underwent successful operation for the ventricular septal perforation
      (VSP) and mitral regurgitation (MR) caused by acute myocardial infarction (AMI)
      are reported. Patch closure of VSP and mitral annuloplasty (MAP) by Kay-Suzuki
      method were performed. Location of VSP were posterior ventricular septum and
      moderate MR were detected in both cases. Case 1 was a 74-year-old man. Four weeks
      after AMI, patch closure of VSP through right ventricular approach and MAP
      through trans-atrial approach and also aorto-coronary bypass to left anterior
      descending artery were performed. Doppler echocardiography was effective to
      evaluate the severity of VSP and MR. Case 2 was a 69-year-old man. Eight days
      after AMI, patch closure of VSP and MAP were performed through biventricular
      approach. Postoperative examination revealed the disappearance of left-to-right
      shunt and MR in both cases. These cases operated successfully were thought to be
      rare.

PMID- 7561315
TI  - [Emergency CABG and mitral valve replacement for anterolateral papillary muscle
      rupture after acute myocardial infarction].
AB  - A 74-year-old man developed sudden cardiogenic shock 5 days after the onset of
      acute myocardial infarction. Echocardiographic diagnosis was severe mitral
      regurgitation due to papillary muscle rupture. Despite the effort to support the
      hemodynamics with catecholamines and IABP, the patient's condition deteriorated
      rapidly, which necessitated emergency operation. Anterolateral papillary muscle
      was found to be totally ruptured. Coronary artery revascularization and mitral
      valve replacement were performed. Postoperative course was uneventful, with two
      days of IABP and three days of ventilatory support. The patient could start
      rehabilitation program on the 7th postoperative day. He was discharged in 2
      months in NYHA class I. Reports of successful emergency operation for total
      papillary muscle rupture following acute myocardial infarction are rare.
      Involvement of anterolateral papillary muscle is rarer. Early diagnosis and
      surgical treatment are mandatory to save this group of patients.

PMID- 7561316
TI  - [Left ventricular pseudoaneurysm at the apex--a case report of successful
      resection of the enlarging pseudoaneurysm following mitral valve replacement,
      which was caused by closed mitral commissurotomy 23 years ago].
AB  - A 47-year-old male with pseudoaneurysm of the left ventricle secondary to mitral
      valve replacement was herein reported because of its unique etiology. The
      pseudoaneurysm was presumably resulted from the mitral valve dilator wound at the
      apex of the left ventricle, which was produced by closed mitral commissurotomy 23
      years ago. To our knowledge, it seems to be a rare reported case with
      pseudoaneurysm of the left ventricle caused by closed transventricular mitral
      commissurotomy.

PMID- 7561317
TI  - [A case report of bentall type operation for annuloaortic ectasia with anomalous
      origin of the right coronary artery complicated by aortic dissection].
AB  - A 49-year-old woman of Marfan's syndrome, who had undergone replacement of the
      thoracoabdominal aorta for Stanford B type aortic dissection at 47 years of age,
      developed Stanford A type aortic dissection with annulo-aortic ectasia and aortic
      regurgitation. At the time of operation, anomalous origin of the right coronary
      artery from the left sinus of Valsalva and near site of the left coronary orifice
      were found. Then, composite graft replacement of the ascending aorta and aortic
      valve, in which a single graft of 16 mm in diameter was interposed between the
      coronary ostia and composite graft, was performed. Anomalous origin of the right
      coronary artery from the left sinus of Valsalva is a rare congenital abnormality.
      It is a matter how to reconstruct the coronary circulation for this type of
      operation. This technique was useful to reconstruct the aortic root even when an
      anomalous origin of the coronary artery existed.

PMID- 7561318
TI  - [Successful surgical repair of subepicardial aneurysm developing as a late
      complication of mitral valve replacement].
AB  - A 60-year-old man who undergone uneventful mitral valve replacement 9 years and 5
      months previously was referred to us because his chest roentgenogram showed
      rapidly growing abnormal shadow. Two-dimensional echo cardiography revealed a
      left ventricular pseudoaneurysm. Emergent surgery was performed under the
      cardiopulmonary bypass. The aneurysm, which arose posteriorly from the base of
      the left ventricle, had a thin wall that could be separated from the pericardium.
      It was therefore diagnosed to be a subepicardial aneurysm. Examination of his
      previously implanted mitral prosthesis (a Duromedicus valve) revealed that the
      mitral orifice was partially occluded by a thrombus. The Duromecicus valve was
      therefore removed, and the ruptured left ventricular wall was closed from both
      outside and inside. A St. Jude Medical valve was then placed in the mitral
      position. Pseudoaneurysm or subepicardial aneurysm formation is a possible late
      complication after mitral valve replacement. Physicians and surgeons should be
      aware of this late complication in patients who had undergone mitral valve
      replacement because it urgently requires surgical correction.

PMID- 7561319
TI  - [A case report of primary pulmonary artery sarcoma].
AB  - A 49-year-old man was admitted because of dyspnea and generalized edema. CT scan
      pulmonary scintigram and cardiac catheter examination revealed pulmonary arterial
      obstruction due to a tumor associated with right heart failure. The tumor was
      extirpated as much as possible by a pulmonary arteriotomy under cardiopulmonary
      bypass. Postoperatively, right ventricular pressure decreased to about 40 mmHg
      while PO2 increased to the normal level. Histological examination of the tumor
      revealed rhabdomyosarcoma arising from the pulmonary artery. Chemotherapy
      consisting of a single course of CDDP and adriamycin was administered.

PMID- 7561320
TI  - [A case of massive air embolism during cardiopulmonary bypass].
AB  - Massive air embolism during cardiopulmonary bypass is one of the most serious
      complications in open heart surgery. We report such an accident, which was
      managed by temporary retrograde perfusion through the superior vena cava. A 59
      year-old woman with severe mitral stenosis underwent mitral valve replacement.
      Soon after the start of the bypass, a massive air embolism occurred, probably
      because a bend in the tubing caused the blood level in the oxygenator to fall.
      The pump was stopped immediately and the patient was placed in the deep
      Trendelenburg position. The pump circuit was primed rapidly with fluid and
      retrograde perfusion through the superior vena cava was done at a flow rate of
      1.5 L/min for 5 min. After air return from the aortotomy was confirmed, the
      standard bypass procedure was resumed with hypothermia. When the accident was
      discovered, and until the end of the operation, deep anesthesia was induced with
      pentobarbital for protection of the brain. Mitral valve replacement and tricuspid
      annuoplasty were done in the usual way thereafter. Postoperatively, the patient
      had no neurologic sequelae except for transient generalized convulsions, and has
      returned to normal daily activities.

PMID- 7561323
TI  - [Intrathoracic transposition of the musculocutaneous flap in treating empyema].
AB  - A 62-year-old woman suffered right empyema caused by methicillin-resistant
      staphylococcus aureus (MRSA) which occurred following a pancreatico-duodenectomy.
      After open drainage thoracotomy, intrathoracic transposition of the extended
      musculocutaneous (MC) flap of the latissimus dorsi was performed. The patient is
      now in good health, without recurrence of either the empyema or the carcinoma, 19
      months after the operation. The MC flap, compared to muscle flap, has the
      advantages that (1) larger empyema cavities can be obliterated, and (2) the
      deformity of the thoracic wall can be minimized, because of the small range of
      resected rib segments and well-preserved volume of subcutaneous tissue in the
      flap long after transposition.

PMID- 7561321
TI  - [A surgical case report of isolated congenital tricuspid valve insufficiency].
AB  - A 17-year-old boy observed as a case with Ebstein's anomaly. Echocardiogram and
      ventriculogram revealed enlargement of the tricuspid valve ring, dysplasia of
      anterior and posterior leaflet of tricuspid valve, but the anatomy of the septal
      leaflet was almost normal. According to these findings, the diagnosis of this
      patient was isolated congenital tricuspid regurgitation. Tricuspid annuloplasty
      of DeVaga's method and Reed's method were done. Post-operative residual
      regurgitation was mild. These procedures were resulting in a successful course.
      Isolated congenital tricuspid valve insufficiency was extremely rare. Only 7
      cases of isolated congenital tricuspid insufficiency successfully operated in
      Japan were collected.

PMID- 7561322
TI  - [Coronary artery bypass grafting without cardiopulmonary bypass in patients with
      LV dysfunction (EF < or = 30%)--a report of 3 cases].
AB  - The purpose of this article is to describe our technique for performing coronary
      artery bypass grafting without cardiopulmonary bypass and to demonstrate that
      this operation is safe and useful to the case of LV dysfunction. Between April
      1988 and March 1994, 2 men and 1 woman aged 61 to 69 years (mean 65 years) with
      LV dysfunction (EF < or = 30%) underwent coronary artery bypass grafting without
      cardiopulmonary bypass. Saphenous vein grafts were placed to the right coronary
      artery (n = 2), left anterior descending artery (n = 2), and internal thoracic
      artery grafts were placed to the right coronary artery (n = 1), left anterior
      descending artery (n = 1). The post operative course were uneventful in all
      patients and discharged with no complications. All patients underwent coronary
      angiography, and 5 of 6 (83.3%) grafts placed without cardiopulmonary bypass were
      patent. In selected patients, coronary artery bypass grafting to the case of LV
      dysfunction without cardiopulmonary bypass can be performed safe and satisfactory
      graft patency rates.

PMID- 7561324
TI  - [Mitral and aortic annular enlargement for small mitral annulus after mitral
      annuloplasty].
AB  - Mitral and Aortic valve rings were enlarged in a 70-year-old female with tiny
      mitral annulus after mitral annuloplasty before. She had undergone aortic valve
      replacement with No. 21 SJM valve and Kay's annuloplasty 10 years previously. The
      reoperation was needed because of mitral stenosis and tricuspid regurgitation. We
      applied the Manouguian technique for the enlargement of the mitral annulus
      because it was too small to implant a prosthetic valve, even though the Aortic
      prosthetic valve was functioning well. As too tight a mitral annuloplasty may
      make the possibility of mitral stenosis real, we should make the annulus remain
      wide enough.

PMID- 7561325
TI  - [A case of secondary valve replacement caused by pulmonary bioprosthetic valve
      endocarditis].
AB  - A 42-year-old male with pulmonary bioprosthetic valve endocarditis accompanied by
      residual minor leakage through a previously closed patch for ventricular septal
      defect (VSD), underwent reoperation with a Carpentier-Edwards bioprosthetic
      valve. The patient had a history of pulmonary valve replacement and VSD in 1973.
      A massive vegetation on the pulmonary valve was demonstrated by echocardiography.
      Five repeated blood cultures yielded Eikenella corrodens. After medical
      treatment, reoperation was performed. The patient was free of complications after
      the procedure. Although bioprosthetic valves have potential problems of
      dysfunction and calcification in long-term use, these problems develop at a
      significantly slower rate in right-sided positions compared with left-sided
      positions and bioprosthetic valve thrombosis in the pulmonary position has
      apparently not been reported. Mechanical prostheses for pulmonary valve
      replacement have a poor prognosis, with a high incidence of valve thrombosis
      despite adequate anticoagulant therapy. For the replacement of prosthetic valves
      in right-sided positions (tricuspid and pulmonary), bioprosthetic valves are now
      our first choice.

PMID- 7561326
TI  - [Rupture of dissecting aortic aneurysm associated with the right-sided aortic
      arch and anomalous course of the left brachiocephalic vein--a case report].
AB  - A case of ruptured dissecting aortic aneurysm (DeBakey IIIb) associated with the
      right sided aortic arch and anomalous course of the left branchiocephalic vein
      was reported. A sixty-nine-year-old female suddenly had the severe back pain and
      soon fell into shock. The diagnosis of a ruptured dissecting aortic aneurysm
      associated with the right sided aortic was obtained on CT scanning. CT films also
      showed the left brachiocephalic vein behind the ascending aorta. Emergency
      operation was performed through median sternotomy and left thoracotomy. The
      descending aorta, forming an aneurysm with the aberrant subclavian artery,
      prominently protruded far to the left, and was located behind the trachea and the
      esophagus. Extra-anatomical bypass grafting was performed between the ascending
      aorta and the distal descending aorta. The patient eventually died of multiple
      organ failure on the 11th day after operation. These findings were confirmed by
      autopsy. A rare vascular anomaly with aortic dissection was reported, and a
      surgical approach to that lesion was discussed.

PMID- 7561327
TI  - [Mitral valve replacement for congenital parachute mitral valve].
AB  - A one-year-old boy was admitted with refractory congestive biventricular heart
      failure for medical treatment. On echocardiogram and cardiac catheterization
      revealed severe mitral stenosis from parachute deformity with pulmonary
      hypertension. During the operation, a single round orifice of 7 mm in diameter
      was detected in the mitral valve and adhered chordae were attached to a large
      single papillary muscle which was located at the posteromedial portion of the
      left ventricle. An isolated muscle band which was not attached to the mitral
      valve was observed at the anterolateral wall of the left ventricle. The mitral
      valve was replaced with 16 mm Carbo-Medicus prosthesis. Postoperative
      catheterization revealed residual pulmonary hypertension which was responsive to
      Imidarine infusion. He was discharged from the hospital without any sequelae, and
      has been on regimen including anticoaglant and vasodilator.

PMID- 7561329
TI  - [Evaluation of serum granulocyte colony stimulating factor and granulocyte counts
      in patients with extracorporeal circulation].
AB  - To clarify the physiologic roles of granulocyte colony stimulating factor (G-CSF)
      in increasing granulocyte after extracorporeal circulation (ECC). The serum
      levels of G-CSF, C3a, granulocyte elastase and granulocyte count were examined in
      26 patients undergone open heart surgery. These patients were divided into two
      groups, the long perfusion group (11 patients) and the short perfusion group (15
      patients). Granulocyte increased immediately after ECC and reached maximum 48
      hours after ECC in both groups. C3a showed significant increase at the end of ECC
      and decreased rapidly after ECC in both group. G-CSF showed high levels 3 and 6
      hours after ECC in the short perfusion group and moderate increase prolonged
      until 48 hours after ECC in the long perfusion group. Granulocyte elastase showed
      high levels 6 hours after ECC and decreased to the normal value 48 hours after
      ECC in the short perfusion group, and high levels prolonging until 48 hours after
      ECC in the long perfusion group. Increase of granulocyte count might be affected
      with increase of compliment (C3a) and G-CSF at the early and late phase after
      ECC, respectively. Granulocyte elastase increased differently by the duration of
      perfusion time.

PMID- 7561328
TI  - [Surgical treatment of apical invading lung cancer].
AB  - Operative technique and long-term results of seventeen patients with apical
      invading lung cancers were evaluated. External radiation therapy was administered
      preoperatively in all but one. Thirteen lobectomies, three wedge resections and
      one pneumonectomy were performed with combined resections of chest wall (and
      adjacent structures) 12, vertebra 3, brachicephalic vein 2, subclavian artery 1,
      lower part of brachial plexsus 3, sympathetic trunk 2 and phrenic nerve 1. Chest
      walls were reconstructed with marlex meshes in 5, the subclavian artery and one
      brachiocephalic vein were with artificial grafts. Operations were considered
      relative curative in 10, relative non-curative in 2 and absolutely non-curative
      in 5. Absolutely non-curative operations were due to cancer-positive stump of
      brachial plexus in the apex in four and metastatic lymph node invading aorta in
      one. Over all five-year survival rate was 35.3% and median survival was 20
      months. Five-year survivals in patients with curative operations and non-curative
      operations were 60% and 0%, respectively, and the former was significantly
      higher. Surgical margin is a large factor for long-term result and invasion to
      the brachial plexus is thought to be a limiting factor for surgery.

PMID- 7561331
TI  - [Cryosurgical ablation of the atrioventricular conduction system--experimental
      study for the determination of the appropriate ablation site and the long term
      follow-up results with clinical application].
AB  - In a series of experimental studies in dogs, we determined the exact site for the
      disruption of the atrioventricular conduction system by cryosurgical ablation
      which does not disturb the intraventricular conduction. The long-term symptomatic
      effects were evaluated in 9 patients with supraventricular tachycardia. In a
      total of 15 adult mongrel dogs, a thoracotomy was performed under pentobarbital
      anesthesia that was maintained during the procedure with artificial ventilation
      and cardiopulmonary bypass. The body temperature was maintained at 37 degrees C
      and throughout each experiment, the ECG was recorded by the conventional limb
      lead method while monitoring and recording the His bundle potentials from the
      catheter-electrode introduced via the internal carotid artery. The location in
      which the maximum His bundle potential was recorded was determined by
      intraoperative His bundle mapping through the right atrial incision. Cryoablation
      was performed by using -60 degrees C probes with a 5 mm tips. In 5 dogs
      (experiment A), we compared the effect of cryoablation at 2 different points on
      the interatrial septum, which were either 10 mm (10 mm point) or 5 mm (5 mm
      point) away from the site of the largest His bundle potential to the direction of
      the coronary sinus ostium. The two ablations were performed successively at 20
      minute intervals. A second group consisting of 10 dogs, received cryoablation
      only at the 5 mm point (experiment B). In experiment A, atrioventricular block
      (AV block) was inconsistently achieved following cryoablation at the 10 mm point,
      whereas at the 5 mm point, the procedure was 100% successful in obtaining AV
      block without affecting the QRS morphology or H-V interval. In experiment B, we
      confirmed the reliability of the 5 mm point. Following cryoablation at the 5 mm
      point, coagulation necrosis in the region from the AV node to the penetrating
      portion of the His bundle were observed by pathological examination, however, the
      damage was only mild at the branching portion of the His bundle. Cryoablation was
      performed at the 5 mm point in 9 subjects. In all of these cases, complete AV
      block was successfully produced to terminate the tachycardias. The R-R interval
      of the escape rhythm in these patients gradually prolonged, and stabilized at
      1500-1600 ms 3 years following the operation. In the long-term
      electrophysiological studies, all subjects had A-H block, and there were no
      subjects with prolonged H-V intervals observed. We conclude that cryoablation at
      the 5 mm point is an appropriate and effective choice for the treatment of
      supraventricular tachycardias.

PMID- 7561332
TI  - [Sarcoplasmic reticular calcium release and myocardial protection--effects of
      ryanodine and cold cristalloid cardioplegia on hypothermic global ischemia].
AB  - Myocardial rapid cooling is known to result in sarcoplasmic reticular (SR)
      calcium release. SR calcium release during an infusion of cold cardioplegic
      solution may contribute to myocardial protection against hypothermic global
      ischemia. We have, therefore, investigated using the isolated working rat heart
      preparation to determine the effect of cold cristalloid cardioplegic solution (K+
      = 16 mmol/L) containing ryanodine on myocardial injury due to hypothermic global
      ischemia. Hearts (n = 6-12/group) from male Wistar rats were aerobically (37
      degrees C) perfused (20 min) with bicarbonate buffer (Ca2+ = 2.4 mmol/L). This
      was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution
      (20 degrees C) containing various concentrations of ryanodine. Hearts were then
      subjected to 180 min of hypothermic (20 degrees C) global ischemia and 35 min of
      normothermic (37 degrees C) reperfusion (15 min Langendorff, 20 min working). The
      recoveries of aortic flow were 46.4 +/- 3.7% in the ryanodine free controls
      versus 50.8 +/- 5.1, 50.6 +/- 4.8, 53.1 +/- 5.9, 59.4 +/- 1.9, 50.5 +/- 3.2 and
      31.8 +/- 6.1% in the 0.18, 0.88, 1.31, 1.75, 10.00 and 100.00 nmol/L ryanodine
      groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561330
TI  - [Isolated aortic valve regurgitation due to degeneration of the valve leaflet--a
      clinical study].
AB  - From 1989 through 1993 thirty-eight patients underwent aortic valve replacement
      at our institution for isolated aortic regurgitation (AR) caused by idiopathic
      degeneration of the valve. There were 32 male and 6 female patients aged between
      33 and 74 years with a mean of 59 years. Preoperative New York Heart Association
      functional class, cardiothoracic ratio, cardiac index, and left ventricular end
      diastolic pressure were 2.6, 57%, 3.1 L/min/m2, and 18 mmHg, respectively. Cross
      sectional echocardiography clarified aortic valve prolapse in seven patients.
      Excised valvular cusps were thin, redundant and translucent in association with
      cuspal fenestration in 9 cases and idiopathic commissural disruption in 2 cases.
      Histological study revealed significant disruption of the fibrosa and cystic
      degeneration of the spongiosa layer filled with mucopolysaccharide. Actuarial
      survival rate, including 3 operative deaths, was 89% at 3 years after AVR with no
      apparent valve related complications. Idiopathic degeneration of the aortic valve
      is a common cause of AR, occurring in half of the surgically treated patients. We
      emphasize the importance of this lesion as a cause of AR.

PMID- 7561333
TI  - [The effects of glucose and insulin upon functional recovery in the rat heart
      preserved by continuous perfusion with St. Thomas' Hospital cardioplegic
      solution].
AB  - The aim of this study was to determine the effect of the continuous perfusion
      with Krebs-Henseleit bicarbonate buffer (KHBB) solution or St. Thomas' Hospital
      cardioplegic solution (ST solution) containing glucose and insulin upon the post
      preservation recovery in the isolated rat heart. METHODS: Hearts from male Wistar
      rats (n = 6/group) were subjected to working perfusion with KHBB solution for
      measurement of cardiac function. They were continuously perfused (1) with KHBB
      solution or ST solution for 12 hours at 20 degrees C, (2) with ST solution for 12
      hours at 37 degrees C, 20 degrees C or 4 degrees C, (3) with ST solution or ST
      solution containing glucose (9 mmol/L) for 12 hours at 20 degrees C or 4 degrees
      C, and (4) with ST solution containing glucose (9 mmol/L) or ST solution
      containing glucose (9 mmol/L) and insulin (10 U/L solution) for 20 hours at 20
      degrees C. This was followed by 15 min of Langendorff perfusion and 20 min of
      working perfusion with KHBB solution. During the second working perfusion after
      preservation, cardiac function was measured again. RESULTS: (1) Percent
      recoveries of cardiac output (%CO) preserved with KHBB and ST solution were 44.9
      +/- 4.0 and 57.7 +/- 3.8%, respectively (p < 0.05). (2) %CO after preservation
      with ST solution at 37, 20, 4 degrees C were 0*, 57.7 +/- 3.8 and 74.4 +/- 2.2*%,
      respectively (*p < 0.05 vs the 20 degrees C group). (3) At 20 degrees C, glucose
      addition to ST solution increased %CO to 76.5 +/- 2.4% from 57.7 +/- 3.8% in
      glucose-free ST solution group (p < 0.05). However, at 4 degrees C, glucose
      addition to ST solution was rather harmful and decreased %CO to 61.4 +/- 2.8%
      from 74.4 +/- 2.2 in glucose-free ST solution group (p < 0.05). (4) The addition
      of insulin to the glucose-containing ST solution resulted in a significant
      increase in %CO from 24.6 +/- 4.0% in the insulin-free solution to 69.2 +/- 2.0%.
      CONCLUSIONS: Our results indicate that 1) ST solution might be better than KHBB
      solution for a continuous perfusion medium of myocardial preservation, and 2) at
      20 degrees C, the addition of glucose and insulin to the ST solution could be
      beneficial for the continuous infusion as a method of preservation, however, at 4
      degrees C, these addition might be harmful, suggesting the temperature dependence
      in the utility of energy substrate.

PMID- 7561334
TI  - [Evaluation of internal thoracic artery bypass grafting with perfusion contrast
      echocardiography].
AB  - Intraoperative perfusion contrast echocardiography (PCE) is a new method to
      evaluate regional myocardial perfusion using Albunx (air encapsulated albumin
      microspheres-Molecular Biosystems, Inc.) and has been employed by direct
      individual injection into human saphenous vein coronary bypass grafts. Because
      this is not an appropriate technique for assessing left internal thoracic artery
      (LITA) graft, we tested the hypothesis that PCE can be performed with a single
      aortic root injection and, thereby, provide regional perfusion data for LITA and
      native coronary flow. CABG (LITA to the left anterior descending artery (LAD) was
      performed in adult swine. PCE was performed in each of the following conditions:
      1) LITA occluded, LAD 100% flow; 2) LITA 100% flow, LAD occluded; 3) LITA 50%
      flow, LAD occluded; and 4) LITA and LAD occluded. Time-intensity curves were
      constructed to assess the time to initial appearance of myocardial enhancement
      (TIA), peak contrast intensity (PI), and area under the enhancement curve (AUC).
      In 12/14 cases, (85.7%), adequate enhancement was achieved. LITA perfusion, when
      compared to perfusion through the native LAD, showed delayed appearance (TIA 0.4
      +/- 0.1 vs 1.9 +/- 0.2 secs), reduced PI (43 +/- 3 vs 28 +/- 3 AU) and reduced
      AUC (247 +/- 115 +/- 19 AU) (p < 0.01) when LITA flow was reduced 50%, TIA was
      prolonged (1.7 +/- 0.2 vs 2.4 +/- 0.2 secs) and AUC was reduced (152 +/- 18 vs 88
      +/- 20 AU) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561335
TI  - [Clinical study on the ideal temperature of blood cardioplegic solution in
      coronary artery bypass graft surgery].
AB  - The effect of myocardial protection in coronary artery bypass graft surgery was
      evaluated from enzymatic examination and cardiac function to clarify the ideal
      temperature of blood cardioplegic perfusate (BCP). The surgical cases were
      divided into two groups from the temperature of BCP; 8 degrees C BCP in 64 cases
      (Group I) and 20 degrees C BCP in 64 cases (Group II). Peak total creatine-Kinase
      (CK) and CK-MB fraction were significantly elevated in Group I than in Group II.
      The value of CK-MB was 79 +/- 79 IU/L in Group I and 37 +/- 26 IU/L in Group II
      (p < 0.01). The parameters of cardiac function were measured from radio-isotope
      (RI) ventriculography in the 35 cases with depressed ejection fraction and
      elevated left ventricular end-diastolic pressure (17 cases in Group I and 18
      cases in Group II). Postoperative parameters such as ejection fraction, first
      third ejection fraction, peak ejection rate and early diastolic peak filling rate
      improved more significantly than preoperative values in Group II, although these
      parameters did not improve in Group I. From these results, 20 degrees C BCP
      provided excellent myocardial protection to arrested heart during coronary artery
      bypass surgery probably because of decreased viscosity of BCP and adequate oxygen
      carrying capacity to myocardium.

PMID- 7561336
TI  - [Flow competition of right gastroepiploic artery graft in coronary artery bypass
      surgery].
AB  - We evaluated the competitive flow between the right gastroepiploic artery (RGEA)
      and native coronary artery in coronary artery bypass surgery with respect to
      anastomosis in a retrograde fashion and the relationship of the degree of
      proximal stenosis with the flow dependency. The RGEA has been used in 157
      patients and was anastomosed in a retrograde fashion in 22 patients. There was no
      significant difference between the retrograde anastomosis and the antegrade
      anastomosis on revascularization to the left anterior descending coronary artery
      in terms of diameter (2.0 +/- 0.5, 1.68 +/- 0.2 mm), flow (21.8 +/- 13.2, 24.5 +/
      19.4 ml/min), early patency (100%, 100%) and string sign (0%, 0%). We examined
      angiographically the relationship between the preoperative degree of proximal
      stenosis and postoperative pattern of flow dependency in the right coronary
      artery distal to the RGEA anastomosis in 98 patients. With a proximal stenosis of
      75% (n = 19), RGEA occlusion was observed in two patients (11%), native coronary
      dependent flow in four (21%), balanced flow in nine (47%) and RGEA-dependent flow
      in four (21%). With a proximal stenosis of 90% (n = 16), native-dependent flow
      was observed in one (6%), balanced flow in six (38%) and RGEA-dependent flow in
      nine (56%) patients. With a proximal stenosis of 99%-100% (n = 63), RGEA
      occlusion was observed in three (5%) and RGEA-dependent flow in sixty (95%)
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561337
TI  - [The 68th Congress of the Japanese Biochemical Society. Sendai City, Japan.
      September 15-18, 1995. Abstracts].

PMID- 7561338
TI  - Lifespan of lymphocytes.
AB  - T and B lymphocytes comprise heterogeneous populations of cells at various stages
      of differentiation and activation. T- and B-cell subsets have different roles in
      the maintenance of immune homeostasis, and their functional differences are
      reflected by their respective lifespans. This review briefly summarizes the
      available data on lymphocyte lifespan, including the kinetics of T- and B-cell
      development in the primary lymphoid organs and the proliferative behavior of
      naive, effector and memory lymphocytes in the peripheral lymphoid compartment.

PMID- 7561343
TI  - [Congenital dislocation of the hip: a sonographic study].
AB  - To investigate congenital dislocation of the hip, we reviewed the clinical
      records, radiographs, sonograms and arthrograms in 106 neonates and infants. In a
      series of 212 hips, 122 were normal, 42 were dysplastic, 16 were subluxed, and 32
      were dislocated. We compared the efficacy of sonography with that of arthrography
      in diagnosing CDH (congenital dislocation of the hip). The mean age in our series
      ws 3.3 months (range: 2 weeks to 12 months). The radiographic, arthrographic, and
      sonographic findings were classified according to the methods of Ishida, Yamada
      and of Graf respectively. We compared the radiographs to the sonograms, and found
      that the diagnostic accuracy of the sonograms was 84.9%, sensitivity was 75.6%,
      and specificity was 91.8%. The discrepancy between the radiographs to the
      sonography was related to the pelvic rotation. Morphologically, there was a close
      correlation between the hip sonography and arthrography. We found that sonography
      in CDH could predict the reduction achievable by a Pavlik-harness as well as
      could arthrography. We concluded that sonography was as useful as arthrography
      for CDH.

PMID- 7561341
TI  - Superantigenic characteristics of mouse mammary tumor viruses play a critical
      role in susceptibility to infection in mice.
AB  - Mouse mammary tumor viruses (MMTV) are retroviruses that induce mammary
      carcinomas. An interesting feature of these viruses is the superantigen (SAg)
      encoded in an open reading frame within the 3' long terminal repeat. The
      mechanism by which ingestion of milk-borne virus results in infection of the host
      mammary tissue remains incompletely understood. However, a working model has been
      proposed in which the interaction between viral SAg, T-cell receptor and MHC
      class II I-E facilitates viral replication and hence infectivity. In this review
      we summarize current studies demonstrating the role of SAg stimulation in
      susceptibility to MMTV infection.

PMID- 7561344
TI  - In vivo wear of bipolar endoprosthesis.
AB  - In vivo wear was evaluated in 39 bipolar endoprostheses retrieved at revision
      surgery. The duration from the implantation until the revision surgery was 5.2 +/
      1.3 years. The annual wear rate of the inner articulation was 0.21 mm, and the
      annual wear rate (in depth) of the polyethylene rim was 0.54 mm. The annual wear
      rate of the rim was greater in cases with radiological osteolysis than in those
      without osteolysis. Improvement in the configuration of the rim, and the device
      such as coating the stem neck with a cobalt-chromium alloy mirror surface are
      necessary to prevent rim abrasion. It is also important to make careful
      consideration on the indication of bipolar endoprosthesis especially for cases of
      dysplastic osteoarthritis, in which rim abrasion was found to be very severe.

PMID- 7561345
TI  - [Muscle strength and muscle blood flow of the quadriceps muscle].
AB  - This study was conducted to measure muscle blood flow changes during increased
      muscle strength in order to determine what characteristic parameters of muscle
      strength were most closely correlated with increased muscle blood flow. The
      muscle blood flow and muscle strength in the quadriceps femoris were measured
      simultaneously during isokinetic extension of the knee joints in two groups--one
      with knee-joint-disease and the other of healthy volunteers. Muscle blood flow
      was measured by the heated thermocouple technique, while parameters of muscle
      strength were evaluated utilizing curves calculated by a Cybex II. The test
      results showed a positive correlation between parameters of muscle strength (peak
      torque, total work and average power) and peak blood flow. However, both the
      muscle strength and the muscle blood flow values were less in the group with knee
      joint disease than in the group of healthy volunteers. In both groups, the muscle
      blood flow was greatest when the knee was extended at an increased angular
      velocity. Although the muscle blood flow was greatest at this time, only the
      parameter of average power increased while the parameter of peak torque and total
      work decreased. As a result, the average power was correlated most closely with
      the increased muscle blood flow. In patients with a knee joint disease, the
      increase in the muscle blood flow was much higher than expected despite the fact
      that there was little increase in average power during knee movement at an
      increased angular velocity. It appeared that the pathological condition in these
      patients' quadriceps femoris required increased blood flow despite an inability
      of the muscle to perform increased muscle work.

PMID- 7561340
TI  - Peptide binding to MHC class I molecules: implications for antigenic peptide
      prediction.
AB  - The human mayor histocompatibility complex class I molecule HLA-A2 preferentially
      binds peptides that contain Leu at P2 and Val or Leu at the C terminus. The other
      amino acids in the peptide also contribute to binding positively or negatively.
      It is possible to estimate the binding stability of HLA-A2 complexes containing
      particular peptides by applying coefficients, deduced from a large amount of
      binding data, that quantify the relative contribution of each amino acid at each
      position. In this review, we describe the molecular basis for these coefficients
      and demonstrate that estimates of binding stability based on the coefficients are
      generally concordant with experimental measurements of binding affinities.
      Peptides that contained cysteine were predicted less well, possibly because of
      complications resulting from peptide dimerization and oxidation. Apparently,
      peptide binding affinity is largely controlled by the rate of dissociation of the
      HLA/peptide/beta 2-microglobulin complex, whereas the rate of formation of the
      complex has less impact on peptide affinity. Although peptides that bind tightly
      to HLA-A2, including many antigenic peptides bind much more weakly. Therefore, a
      full understanding of why certain peptides are immunodominant will require
      further research.

PMID- 7561342
TI  - Increased expression of complement receptor type 1 (CR1, CD35) on human
      peripheral blood T lymphocytes after polyclonal activation in vitro.
AB  - The receptor for C3b and C4b--complement receptor type 1 (CR1, CD35)--is present
      on a variety of cell types including erythrocytes, phagocytic cells, B
      lymphocytes and a small subpopulation of T lymphocytes. The function of the
      receptor varies according to the different cell types, but on T lymphocytes the
      function is as yet not known. The present study concerns the influence of
      polyclonal stimulation on CR1-expressing T lymphocytes. Incubation with PHA
      resulted in a dose-dependent increase in the number of CR1-positive T
      lymphocytes. The CR1-expression T lymphocytes were found in both the CD4- and the
      CD8-positive subpopulation, but a significant stimulatory increase was only found
      in the CD4-positive population. A significant increase in the number of CR1
      expressing T lymphocytes was found when monocytes were present during
      stimulation, indicating an importance of monocytes and/or monocyte products.
      However, the increase was not regulated by arachidonic acid metabolites of the
      cyclo-oxygenase pathway as indomethacin failed to inhibit the increase. Neither
      did rIL-1 alpha, rIL-1 beta, rTNF alpha nor rIL-6 alter the number of CR1
      expressing T lymphocytes. The results of this study indicate a role for CR1 on T
      lymphocytes in the regulation of the immune system.

PMID- 7561347
TI  - [Analysis of the human wrist motion in three dimensions using a video-digitizer].
AB  - We report the results of a new assessment system (using a Video-digitizer and non
      contact type transducer) in order to clarify the three-dimensional human wrist
      motion. The results of basic experimental studies conducted prior to this
      clinical assessment indicated that this new system was an extremely reliable and
      useful to measure three-dimensional motion. The results of the wrist motion in
      normal individuals showed supination at radial flexion movement, pronation in
      ulnar flexion movement, and pronation in the dorso-ulnar part of rotational
      movement. The comparative results of human wrist motion in pathological
      conditions suggested that an involvement of the distal radio-ulnar joint was
      primarily responsible for impairment in the rotational movement of the human
      wrist.

PMID- 7561346
TI  - [Affinity of estrogen binding in the cultured spinal ligament cells: an in vitro
      study using cells from spinal ligament ossification patients].
AB  - This immunological study investigated the effects of estrogen as a potential
      causative factor for spinal ligament ossification (such as ossification of the
      posterior longitudinal ligament, OPLL; ossification of the yellow ligament, OYL;
      and ossification of the anterior longitudinal ligament, OALL). The serum total
      estrogen (estron + estradiol + estriol) level in the OPLL patients and controls
      was measured by radioimmunoassay. To determine any difference in the affinity of
      the estrogen, 3,17 beta-estradiol receptors of cultured spinal ligament cells
      obtained from OPLL patient were detected by receptor binding assay, and compared
      with cells from controls. Additionally, to evaluate the responses of cultured
      spinal ligament cells to stimulation by 3,17 beta-estradiol, examined the
      production of bone Gla protein (BGP) in medium, the rate of tritiated thymidine
      (3H-TdR) uptake, and change in affinity of transforming growth factor-beta 1 (TGF
      beta 1) receptor on those cells with 3,17 beta-estradiol added (E2+ group), and
      compared the results with those when 3,17 beta-estradiol was not added (E2-
      group). The serum total estrogen level was significantly higher in OPLL patients
      than in controls, and the level increased with increasing extent of ligament
      ossification. Cultured cells obtained from OPLL patients had receptors with a
      higher affinity for 3,17 beta-estradiol than did cells from controls. Cells
      obtained from OPLL patients responded to the stimulation by 3,17 beta-estradiol,
      accelerated BGP production, and elevated the 3H-TdR uptake. However, cells from
      controls showed no change in the stimulation by 3,17 beta-estradiol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7561348
TI  - [Effects of fibular malunion on contact area and stress distribution at the ankle
      with six simulated loading conditions].
AB  - A shortened, externally rotated malunion in the lateral malleolus following an
      ankle fracture-dislocation often causes post-traumatic degenerative arthrosis
      even without talar displacement (occult malunion). The purpose of this study was
      to examine the effect of malalignment of the fibula on stress distribution in the
      ankle joint using two grades of pressure sensitive film (super-low and low) as a
      transducer. The ankles of seven amputated lower legs were mounted in an MTS
      machine, then loaded in 6 different positions of 3 single leg stance positions at
      the neutral, abduction and adduction of the foot, and 3 simulated positions in
      the stance phase of walking. A normal ankle, an ankle with 5 mm shortened fibula
      only, and an ankle with a shortened fibula plus an additional 20 degrees external
      rotation of the fibula were tested. Talar shift was examined on X-ray, before and
      after each test. When the fibula was shortened, and after additional external
      rotation, there was no talar shift even after loading and the total contact area
      was not significantly different from normal, however, there was the stress
      increase on the lateral side of the tibio-talar joint, with the area of higher
      stress range significantly larger than normal. There was no significant
      difference between the ankle with a shortened fibula only and that with an
      additional 20 degrees external rotation. The stress change in the fibular
      malalignment was concluded to be mainly due to the shortened fibula. It seems
      that the shortened lateral malleoli affect the ankle joint regardless of the
      talar shift and may induce degenerative arthrosis.

PMID- 7561339
TI  - Immunology of Theiler's murine encephalomyelitis virus infection.
AB  - Theiler's murine encephalomyelitis virus (TMEV) is a single-stranded RNA virus
      that belongs to the family of picornaviruses. Intracranial inoculation of
      susceptible mouse strains with TMEV results in biphasic disease, consisting of
      early acute disease that resembles poliomyelitis, followed by late chronic
      demyelinating disease that is characterized by the appearance of chronic
      inflammatory demyelinating lesions. Susceptibility to TMEV infection is
      genetically controlled by three loci: one that maps to the H-2D region of the
      major histocompatibility complex, one to the beta-chain constant region of the T
      cell antigen receptor, and one located on chromosome 3. Both early acute and
      chronic late demyelinating diseases are immunologically mediated. T cells appear
      to play an important role in the pathogenesis of the disease. TMEV-induced
      demyelinating disease in mice has extensive similarities with multiple sclerosis,
      and it is considered one of the best experimental animal models for multiple
      sclerosis.

PMID- 7561349
TI  - [Load transmission through the wrist joint: a biomechanical study comparing the
      normal and pathological wrist].
AB  - This study was undertaken to elucidate the correlation, if any, between pressure
      loading and the progress of degenerative osteoarthritis in the human wrist. Nine
      fresh amputated forearms were used to produce i) a pathological model of a
      malunion after a distal radius fracture, ii) a model of a triangular
      fibrocartilage (TFC) tear, and iii) a model of a scapholunate dissociated wrist
      (involving three specimens for each model). On pressure loading, changes in the
      radioulno-carpal joint and in the midcarpal joint were measured using a pressure
      sensor. In the malunion of the distal radial end, we found that a pressure
      fluctuation occurred at more than a 20 degrees dorsal tilt with greater than
      ulnar +2 mm variance. The loads on the TFC surface and on the scaphoid surface
      increased, causing the pressure loading site to move dorsally. In the model of a
      partial TFC resection, sufficient decompression was achieved at the resection
      site for ulnar 0 mm variance. However, at +2.5 mm variance, the pressure loading
      caused a concentrated pressure to occur on the TFC surface and the decompression
      became ineffective. So for a +2.5 mm variance in this model, shortening the ulnar
      diaphysis is suggested as adequate for a clinical reduction in pressure. In the
      scapholunate dissociated model, we observed decreased pressure in the
      radioscaphoid articulation and scaphocapitate articulation, during volar rotation
      of the scaphoid, while there was increased pressure in the radiolunate and in the
      lunocapitate articulation. In all models, the focus of the increased pressure was
      correlated with radiographic findings as being the same as the site of
      morphological degeneration, suggesting a close correlation between abnormal
      pressure and the progression of degenerative osteoarthritis.

PMID- 7561350
TI  - [The solubility of calcium pyrophosphate dihydrate crystals].
AB  - The solubility of calcium pyrophosphate dihydrate crystals (CPPD crystals), which
      cause pseudogout, was studied in vitro and vivo. The in vitro experiment using
      0.1 M tris buffer and 0.2 M glycine buffer indicated that changes in pH and
      pyrophosphatase activity played a major role in the solubility of CPPD crystals.
      An experiment using the synovial fluid from patients with pseudogout, rheumatoid
      arthritis, and from those with osteoarthritis suggested that changes in the
      synovial fluid pH due to inflammation affected the solubility of these crystals.
      In addition, an experiment using the air pouch in rat showed that inflammation
      due to the CPPD crystals was maximum at about 9 hours after CPPD injection, and
      that inflammatory cells appearing at this time then had a major influence on the
      crystals' solubility. From these results, it appeared that CPPD crystals released
      into the joint cavity were mostly dissolved by inflammatory cells, but that
      crystal dissolution was also affected by changes in the synovial fluid itself,
      particularly by a change in pH.

PMID- 7561351
TI  - [Experimental study on the effects of tension-reduced early mobilization on
      extensor tendon healing].
AB  - Numerous clinical and experimental studies have been reported on early
      postoperative mobilization after flexor tendon repair. However, there have been
      only a few experimental studies reported on extensor tendon repair. In 1989,
      Ishiguro reported the usefulness of tension-reduced early mobilization in
      clinical cases of extensor tendon ruptures. The purpose of this experimental
      study was to examine the in vivo effect of tension-reduced early mobilization on
      extensor tendon healing in chicken. An experiment was performed on the extensor
      tendons of 218 chickens in an attempt to examine the effects of tension-reduced
      early mobilization on tendon healing and adhesion. The extensor tendon of the
      fourth toe was cut and the distal stump of the tendon was transferred to the
      extensor tendon of the third toe. Postoperatively two protocols were employed. In
      the immobilization group, a cast was applied for three weeks. In the early
      mobilization group, immediate active motion of the digits was allowed. A tension
      reduced position was maintained by taping the fourth toe to the dorsum of the
      third. The findings from the early mobilization group and from the immobilization
      group were as follows: 1. Macroscopically, sutures at the repair site of the
      early-mobilized tendon were not evident after three weeks because of fibrous
      connective tissue growth. Despite this abundant connective tissue, tendon gliding
      was observed to be smooth. Between the suture site and the gliding floor, loose
      connective tissue, similar to normal paratenon, was observed. Histology confirmed
      this observation. 2. The tensile strength required to extend the MP joint was
      significantly lower for the early-mobilization group than for the immobilization
      group, suggesting minimal adhesion between the sutured tendon and the gliding
      floor in the early-mobilization group. 3. No significant difference in tensile
      strength among the various tendon repair techniques employed was observed at the
      suture site.

PMID- 7561352
TI  - [Experimental changes in BDNF- and NT-3-like immunoreactivities in the spinal
      cord following its transection].
AB  - Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are
      neurotrophic factors involved in the neurotrophin family. However, while their
      biological activities on cultured neurons and their distribution have been
      reported, their functions in the central nervous system including the spinal cord
      are still unknown. We have recently developed antibodies to BDNF and to NT-3
      synthetic peptides with different amino acid sequences as tools to visualize
      these molecules in in vivo tissue. Each antibody was specific to either BDNF or
      NT-3. Using these antibodies, we investigated the distribution of BDNF- or NT-3
      like immunoreactivities (LI) in the spinal cord following transection in rats. In
      Group with an uninjured spinal cord as control, both BDNF-LI and NT-3-LI were
      localized in the gray matter, and particularly in the motor neurons of the
      ventral horn, and in some axons and glial cells of the white matter. In Group
      after transection of the spinal cord as a model of spinal injury, the motor
      neurons in the spinal cord, were strongly stained by anti-NT-3 antibodies and
      less strong by anti-BDNF antibodies at 3 weeks after injury. In the gray matter
      at 4 weeks after injury, astrocyte-like cells were markedly stained with anti
      BDNF antibodies These findings indicate that in the spinal cord after injury, the
      biosynthesis of BDNF was upregulated in a different manner from that of NT-3 and
      that BDNF and NT-3 were both involved in the repair mechanisms, directing the
      amelioration of the spinal cord injury.

PMID- 7561353
TI  - [The effect of neurolysis on the recovery of experimentally induced entrapment
      neuropathy].
AB  - While chronic entrapment neuropathy is a common problem in orthopaedic practice,
      controversy remains over which is the most appropriate surgical procedures. There
      have been few experimental studies addressing this problem. This study was
      undertaken to compare the effects, as well as the risks, of various surgical
      procedures on experimentally induced chronic entrapment neuropathy in rat. Ninety
      adult male Wistar rats (250-300 g) were used as the experimental animals. The
      sciatic nerves were wrapped by silastic tubes each 10 mm long with an internal
      diameter of 1.5 mm. At eight months later, after the nerves had demonstrated
      changes compatible with clinical chronic entrapment neuropathy, the tubes were
      removed and simple decompression, external or internal neurolysis was carried out
      on the entrapped nerve. Nerves at 1, 2, 4 and 6 months after surgery were
      morphologically and functionally examined. Electrophysiological and histological
      changes were gradually ameliorated after simple decompression. The externally
      neurolysed nerve showed improvements in the normal nerve functions. Internal
      neurolysis on chronically entrapped nerves produced a deterioration in the nerve
      functions, as well as in the nerve structures. We concluded that more favorable
      results were achieved by the external neurolysis, whereas internal neurolysis was
      a very harmful procedure for chronic entrapment neuropathy.

PMID- 7561354
TI  - [Regulation of cancellous bone structure by bone remodeling].

PMID- 7561356
TI  - [Concept and classification of immunoglobulin abnormalities].

PMID- 7561355
TI  - [Present status of diagnosis and therapy of patients with multiple myeloma].

PMID- 7561357
TI  - [Immunoglobulin producing mechanism and their abnormalities].

PMID- 7561358
TI  - [Cell division mechanism of multiple myeloma].

PMID- 7561359
TI  - [Immunoglobulin abnormalities].

PMID- 7561360
TI  - [Bone lesions in patients with multiple myeloma].

PMID- 7561362
TI  - [Renal disorders in patients with immunoproliferative disorder].

PMID- 7561361
TI  - [Nerve lesions in patients with immunoproliferative disorders].

PMID- 7561363
TI  - [Immune dysfunctions in patients with immunoproliferative disease].

PMID- 7561364
TI  - [Anemia and hemostasis dysfunction in patients with immunoproliferative
      disorders].

PMID- 7561365
TI  - [Hyperviscosity syndrome in patients with immunoproliferative disorder].

PMID- 7561366
TI  - [Treatment of multiple myeloma].

PMID- 7561367
TI  - [Various immunoproliferative disorders].

PMID- 7561368
TI  - [Immunoglobulin light-chain type amyloidosis].

PMID- 7561369
TI  - [Polyneuritis, endocrine disorders associated with plasma cell dyscrasia].

PMID- 7561370
TI  - [Myeloma cell growth and interleukin 6].

PMID- 7561371
TI  - [Hematopoietic stem cell transplantation in multiple myeloma].

PMID- 7561373
TI  - [Case of Sheehan syndrome with hypoglycemia and adrenal crisis despite normal
      labor].

PMID- 7561372
TI  - [Physiopathology, diagnosis and therapy in multiple myeloma (discussion)].

PMID- 7561374
TI  - [A case of consciousness disorder, convulsion, meningeal stimulation, ocular
      motility disorder and ataxia induced by cyclosporin].

PMID- 7561375
TI  - [A case of meningo-vascular type neurosyphilis presenting oculomotor nerve
      paralysis with interesting MRI findings].

PMID- 7561376
TI  - [A case of hemorrhagic colitis due to E. coli with hemolytic uremic syndrome and
      thrombotic thrombocytopenic purpura].

PMID- 7561378
TI  - [Genetic aspects of hypertension--etiology of essential hypertension].

PMID- 7561379
TI  - [Basic and clinical study of left ventricular remodeling].

PMID- 7561377
TI  - [A case of renal angiomyolipoma with peri-renal hemorrhage].

PMID- 7561380
TI  - [Basic and clinical study of reactive oxygen species].

PMID- 7561381
TI  - [Reality in dealing with sarin poisoning].

PMID- 7561382
TI  - Correlation between thermal radiosensitization and slowly rejoined DNA strand
      breaks in CHO cells.
AB  - The effect on the repair of slowly rejoined strand breaks was studied in CHO
      cells using the alkaline unwinding technique. Heat (45 degrees C, 20 min)
      combined with a X-ray dose of 9 Gy was found to result in an increased half-time
      of repair but also in an increased number of slowly rejoined strand breaks. When
      a time interval at 37 degrees C was inserted between irradiation and heat, the
      half-time of repair was not altered, whereas the number of slowly rejoined strand
      breaks as measured 300 min after irradiation decreased with increasing time
      interval between the two treatments. The half-time of 18 +/- 2 min suggested that
      the additionally formed, slowly rejoined strand breaks arise from a certain type
      of radiation-induced DNA base lesions with repair of which is modified by heat.
      The effect of X-irradiation combined with heat was also studied for cell
      survival. When irradiation and heat were separated by an incubation at 37 degrees
      C, cell survival increased with a half-time of 20 +/- 2 min, which is similar to
      that measured for the number of additional, slowly rejoined strand breaks. For a
      great variety of combined treatments, the reduction in cell survival correlates
      well with the enhanced number of slowly rejoined strand breaks measured 300 min
      after irradiation. This positive correlation and the similarity in the half-times
      mentioned above suggests that thermal radiosensitization results from the number
      of additional, slowly rejoined strand breaks formed when irradiation was combined
      with heat.

PMID- 7561383
TI  - Influence of ara A on the formation of dicentrics in irradiated quiescent CHO
      cells.
AB  - CHO K1-cells, arrested in G0/G1 phase were irradiated with graded doses of 150-kV
      X-rays, and the dicentric chromosome aberrations in the first metaphase after
      reincubation in full growth medium were evaluated. When 500 microM ara A was
      administered at least 1 h before irradiation, maximal enhancement of the
      dicentric yield was obtained under 'immediate plating' conditions as well as
      under 'delayed plating' conditions, and under both conditions only the linear
      component alpha D of the aberration yield was affected. Since ara A had no effect
      upon the number of induced dsbs, as measured with PFGE at doses up to 100 Gy, the
      action pathway of ara A is suggested to be the repair/misrepair process
      manifested in the linear component of the dicentric yield. By varying the time at
      which either ara A at 37 degrees C was administered before irradiation or ara A
      at 4 degrees C was added after irradiation, it was observed that the repair step
      sensitive to ara A was completed within about 5 min after irradiation. This is in
      agreement with other observations of ara A action upon a fast repair step. The
      conversion of DNA single-strand breaks or base damage sites into double-strand
      breaks as a consequence of polymerase beta inhibition by ara A would explain the
      present results.

PMID- 7561384
TI  - Delayed chromosomal instability in human T-lymphocyte clones exposed to ionizing
      radiation.
AB  - Recent studies have demonstrated that cells which survive alpha-particle and X
      ray exposure may show chromosomal instability, i.e. they continue to develop
      chromosomal aberrations at an increased frequency for many division cycles after
      the exposure. To characterize this delayed response, we carried out repeated
      karyotype analyses of X-irradiated T-lymphocytes during clonal expansion in
      vitro. Human peripheral blood lymphocytes were obtained from a healthy donor and
      exposed to 3-Gy X-irradiation. Cell survival, estimated by a cell cloning assay,
      was 5%. Non-irradiated, control cells were studied in parallel. Monoclonal cell
      lines were established using the T-cell cloning procedure. G-band karyotype
      analyses were carried out at several intervals during expansion of the clones for
      up to 2 months. The irradiated clones did not differ from the control clones with
      regard to growth rate or cytometric DNA profile. Non-irradiated cell clones
      showed a normal karyotype, with < 10% of sporadic, non-clonal chromosome and
      chromatid breaks. In the irradiated clones, the karyotypes showed different
      (sub)clonal chromosome rearrangements, which developed successively during the
      cultivation time. In addition to these karyotypic abnormalities, > 20% of the
      cells in these clones had sporadic, non-clonal chromosome aberrations, and there
      was a tendency of increasing frequency of such aberrations by length of
      cultivation. Thus, two types of radiation-induced chromosomal instability were
      observed; (sub)clonal karyotypic abnormalities and sporadic, non-clonal
      chromosome aberrations. The frequency and kinetics by which these alterations
      occur in the progeny of X-irradiated T-cells suggest that they arise through
      different pathways, and argue against their causation by mutation or persistent
      DNA damage.

PMID- 7561385
TI  - Chromosome painting in highly irradiated Chernobyl victims: a follow-up study to
      evaluate the stability of symmetrical translocations and the influence of clonal
      aberrations for retrospective dose estimation.
AB  - Follow-up fluorescence in situ hybridization (FISH) measurements of symmetrical
      translocations were performed in peripheral blood lymphocytes from 12 highly
      irradiated victims of the Chernobyl nuclear power plant accident biannually,
      between September 1991 and July 1994, to investigate the persistence of these
      aberration type with time post-exposure. Translocations were determined using
      biotin-labelled painting DNA probes for human chromosomes 1, 4 and 12 and a
      digoxigenin-labelled alpha-satellite pancentromeric DNA probe. In 11 of 12 cases
      the translocation frequencies remained fairly constant during the observation
      period, which allows to generate comparable dose estimates on the various
      sampling times. In one case (no. 9) the existence of a cell clone containing the
      consistent chromosome rearrangement t(1;13) (q25;q14) was identified using FISH
      in rehybridized slides with a digoxigenin-labelled painting DNA probe for
      chromosome 13 and a separate G-banding analysis. To obtain reliable dose
      estimates, total translocation frequency has to be corrected for the high
      contribution (16.5-23.5%) of this clonal translocation.

PMID- 7561386
TI  - Application of automation to the detection of radiation damage using FISH
      technology.
AB  - A whole chromosome painting approach was employed to highlight the damaging
      effects of low-to-moderate doses of ionizing radiation. A detailed tally of
      damage involving the painted chromosomes 1 and 2 was compiled from visual
      analysis and compared with the results of an automatic image processing approach,
      where the possible outcomes were 'normal', 'abnormal', or 'rejected'. The
      performance of the automatic approach was tested using a set of 9000 bicolour
      metaphase images harvested from whole-blood cell culture following irradiation
      levels of 0.0, 0.5, 1.0 and 2.0 Gy. Every metaphase image in the set was analysed
      visually. The automatic analysis model was based on two simple image criteria to
      distinguish normal from abnormal; either an increase in the number of painted
      objects or a large asymmetry in the area distribution of the expected number of
      painted objects. A result was obtained without a full karyotype analysis. In
      practice, automatic analysis produced a set of images for review that were
      enriched by a factor of 3-4 in true abnormal images. Fast visual review of these
      images (approximately 200/h) selected the true abnormals. A comparison of the
      automatic analysis with the visual analysis showed that automated analysis
      correctly identified 60% of normal cells, 59% of abnormal cells and 73% of
      rejected cells.

PMID- 7561387
TI  - Hsp70 gene expression in mouse lung cells upon chronic gamma-irradiation.
AB  - Elevated levels of hsp70 mRNA in cells of lung, spleen and small intestine have
      been observed upon chronic in vivo gamma-irradiation of mice at a dose-rate of 3
      cGy/day for 30 days. Changes in hsp70 gene expression in lung cells were analysed
      in more detail. Chronic irradiation with an accumulated dose of 48 cGy increased
      the amount of hsp70 mRNA at dose rates of 3 and 6 cGy/day and had no effect on
      hsp70 mRNA level at dose-rates of 1.2 and 12 cGy/day. An increased level of hsp70
      mRNA was observed by day 7 of irradiation at a dose-rate of 3 cGy/day, was high
      by day 30 but by the end of the second month the amount of mRNA dropped to
      control values. Western blotting revealed a higher level of hsp70 protein as
      well, although the amount of protein increased to a lesser degree than that of
      mRNA.

PMID- 7561388
TI  - On the reaction kinetics of the radioadaptive response in cultured mouse cells.
AB  - The reaction kinetics of radioadaptive response of low doses of X-rays have been
      studied in quiescent cultured mouse cells. Mouse m5S cells pre-exposed in G1 to
      low doses of X-rays became insensitive to the induction of chromosome
      aberrations, mutation toward 6-thioguanine resistance, and cell killing. Adapted
      cells were, however, more susceptible to morphological transformation by
      subsequent high challenging doses of X-rays. The cytogenetic adaptation, which
      lasted about 20 h pertained to a narrow dose range. X-ray doses below and above
      0.1 Gy appeared to be recognized as different signals; higher doses of X-rays
      were incapable of inducing adaptation and rapidly extinguished the adapted
      condition. Treatment with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and
      hydrogen peroxide, but not the xanthine/xanthine oxidase superoxide-generating
      system, mimicked X-rays in inducing adaptation when applied at low doses. Over
      exposure to TPA or inhibitors of protein kinase C (PKC) abrogated the adaptive
      response to X-rays, providing evidence for the involvement of a PKC-mediated
      signalling pathway. The lack of radioadaptive response in a tumorigenic variant,
      clone 6110, and its restoration in the morphological revertant obtained by
      introducing human chromosome 11 further suggested that interference of signalling
      pathways may alter radioadaptive responses in malignant cells.

PMID- 7561390
TI  - Expression of transforming growth factor-beta 1 in mouse skin during the acute
      phase of radiation damage.
AB  - Transforming growth factor-beta (TGF beta 1) plays a central role in wound
      healing, so its perturbation by radiation may contribute to the acute and late
      effects seen in irradiated skin. TGF beta 1 mRNA expression was measured by PCR,
      in the skin of the CD1 and CBA mouse, exposed to Sr-90 beta from an 11-mm
      diameter source. TGF beta 1 mRNA expression increased sharply after doses between
      1 and 10 Gy and plateaued at approximately 200% above controls after doses
      between 20 and 50 Gy. Immunohistochemistry showed that the TGF beta 1 protein was
      confined to the dermis and suprabasal cells with none in basal cells. A dose of
      50 Gy produces an acute desquamative reaction in 100% of mice that is resolved in
      30 days. After the same dose, TGF beta 1 mRNA expression fell below the controls
      at 3 h (-9.4% in the CD1 and -44% in the CBA mouse); rose sharply at 6-12 h
      (+124% CD1, +230% CBA), returned to control levels by 24-48 h, then rose
      progressively to approximately 200% above the controls between days 7 and 14. TGF
      beta 1 mRNA expression remained elevated at 100-200% above controls until the end
      of the experiment at 55 days. The significance of these changes in TGF beta 1 is
      discussed in the context of the early stress response reaction to radiation, the
      acute inflammatory and the later chronic fibrosis of the skin.

PMID- 7561389
TI  - UV-A oxidative damage modified by environmental conditions in Escherichia coli.
AB  - The effect of sublethal fluences (50-200 kJ m-2) of UV-A radiation (320-400 nm)
      in bacterial cells is a transient growth inhibition related to photo-modified
      tRNA and is associated with changes in membrane structure and function. Higher UV
      A fluences result in cell death due to the production of reactive oxygen species,
      so far undetected at sublethal doses. Oxidative mechanisms of toxicity induced by
      120 kJ m-2 UV-A radiation can be recorded by ultra-weak chemiluminescence, useful
      in quantifying oxidative reactions. When Escherichia coli was exposed to UV-A
      stress at a fluence rate equivalent to that of the Sun in the biosphere (33 W m
      2), chemiluminescence levels were proportional to the photodamage.
      Chemiluminescence and photo-damage are linearly proportional and dependent on
      environmental conditions of the cells. It is postulated that in addition to tRNA
      photo-modification, UV-A alters the membrane structure of E. coli by oxidative
      damage, since changes in the membrane structure under different environmental
      conditions play a key role in the cell's response to UV-A injury.

PMID- 7561391
TI  - Mixed-field neutrons and gamma photons induce different changes in ileal bacteria
      and correlated sepsis in mice.
AB  - High doses of radiation induce septicaemia, from bacterial translocation, and
      death in animals. Mice were exposed to either comparable lethal (LD90/30) or
      sublethal (LD0/30) doses of mixed-field [n/(n + y) = 0.67] or pure 60Co gamma
      photon radiation. The relative biological effectiveness of these comparable doses
      of radiation was 1.82, determined by probit analysis. Mice given a lethal dose of
      mixed-field radiation developed a significant (p < 0.01), 10(9)-fold increase in
      Gram-negative facultative bacteria in their ilea over values in control mice. In
      contrast, mice given a lethal dose of gamma-photon radiation developed a
      significant (p < 0.01) increase in only Gram-positive bacteria in their ilea,
      while the number of Gram-negative bacteria remained near values in control mice.
      Data correlated with bacteria that were isolated and identified from the livers
      of mice that were given comparable lethal doses (LD99/30) of mixed-field or gamma
      photon radiation. In sublethally irradiated mice, fluctuation in the total number
      of bacteria was detected in their ilea during the first week following
      irradiation, after which the number approximated the value in control mice. This
      difference in the predominant facultative bacteria in ilea resulting from
      different qualities of radiation has important implications for the treatment of
      septicaemic-irradiated hosts.

PMID- 7561392
TI  - Exposure of domestic quail embryos to extremely low frequency magnetic fields.
AB  - Four hundred domestic quail eggs (Coturnix coturnix japonica) were used to study
      the possible teratogenic effects of extremely low frequency magnetic fields (ELF
      MFs) on early embryonic development. Ten females were selected from a flock on
      the basis of their high fertility rate and low number of spontaneous
      abnormalities and they were selectivity maintained in nesting-boxes in a room
      where feeding and environmental conditions were carefully controlled. All the
      eggs used in the experiments were filiated by their progemtor, and were handled
      in the same way from the time they were laid until the point at which they were
      placed in a specially designed incubator, which dramatically reduces the stray
      magnetic fields produced by the heating system. Twenty eggs per experiment (10
      control and 10 exposure) were placed in two different areas within the incubator.
      For each experiment two eggs from each of the 10 females were used. These were
      placed pairwise in the same position in the incubation areas (one in the control
      area and one in the exposure area). The first 12 experiments (240 eggs in total)
      were sham (ELF-MFs source turned off) in order to identify the variability of
      test quantities. The last eight experiments (160 eggs in total) involved magnetic
      fields (continuous bipolar square signal, rise and fall time 4 microseconds, in
      Helmholtz' coils) and they were divided into two exposure groups: the first four
      experiments at 50-Hz frequency and the last four at 100-Hz frequency. The
      magnetic flux density was different for each experiment within each frequency
      group, but the same sequence was always used: 0.2, 1.2, 2.2, 3.2 microtesla. The
      number of abnormal embryos found in the area exposed to 100 Hz was significantly
      higher than for their controls (Chi-square test, p = 0.048) but this difference
      was not significant for the 50-Hz group (p = 0.232). An ANOVA test was
      significant for the magnetic field variable (p < 0.05). A higher number of dead
      embryos was observed in the two groups of exposed eggs. Finally, a gross
      examination of the external morphology of the abnormal exposed embryos showed a
      high percentage of abnormalities of the nervous system, particularly at the
      cephalic level.

PMID- 7561394
TI  - Rad Res 95, the Association for Radiation Research meeting. Saint Andrews, United
      Kingdom, 5-8 April 1995. Abstracts.

PMID- 7561393
TI  - Role of molecular biology in radiation biology.

PMID- 7561395
TI  - Response of cells to radiation sensitizers: methods of analysis.

PMID- 7561396
TI  - An anatomical study of the mechanical interactions of flexor digitorum
      superficialis and profundus and the flexor tendon sheath in zone 2.
AB  - The mechanical interactions of tendon loading and motion between FDS and FDP
      tendons and the distal edge of the A2-pulley (DEA2) were investigated in
      cadaveric hands. The FDP tendon showed a two-stranded contrarotational spiral of
      tendon fibres, their course parallel to the FDS fibres. On loading, the FDP
      tendon changed cross-sectional shape and the two slips of FDS moved closer
      together, applying lateral force on the FDP tendon. The formula DEA2-MCP/proximal
      phalanx length was calculated as 0.64 +/- 0.052 mm/mm. Excursions of bifurca and
      chiasma were measured relative to the DEA2. In full extension the bifurca was
      well proximal to the DEA2, the chiasma always distal. In flexion, the chiasma
      approximated to DEA2 level. Therefore, an additional anteroposterior force should
      exist at DEA2 level between FDS and the DEA2 on the FDP-tendon. The changes in
      tendon shape and the lateral- and anteroposterior forces produce a
      "compressional" mechanism on FDP by FDS which may alter frictional resistance.
      This mechanism is compared with the Chiropteran tendon locking mechanism.

PMID- 7561397
TI  - The double sheath system and tendon gliding in zone 2C.
AB  - Anatomical structures, the morphology of gliding tunnel, the gliding amplitude of
      tendons and the range of finger motion after sheath incision in zone 2C were
      studied in 40 fingers of ten preserved cadaver hands. The tendon of FDS in zone
      2C courses around that of FDP, and FDS serves functionally as a second sheath for
      FDP. This "double sheath" system in zone 2C accounts for the poor results of
      tendon repair in zone 2C. The tendon repairs in zone 2C glide into zone 2D during
      finger flexion. Therefore, the condition of the gliding tunnel of zone 2D is also
      important to the function of tendon repairs in zone 2C. The range of motion was
      shown to be insignificantly influenced by partial incision of the A2 pulley, and
      this did not decrease the total strength of the sheath markedly. These suggest
      that partial incision or enlargement of the A2 pulley can be carried out for
      tendon repairs in zone 2C without causing mechanical problems of function.

PMID- 7561398
TI  - Magnetic resonance imaging of acute tendon injury in the finger.
AB  - Accurate assessment of flexor tendon function in a digit with an acute, non
      penetrating injury is difficult. MR imaging can negate the need for surgical
      exploration and the associated morbidity.

PMID- 7561399
TI  - Magnetic resonance imaging for diagnosis of digital flexor tendon rupture after
      primary repair.
AB  - Because the clinical diagnosis of rupture of a digital flexor tendon was
      uncertain 10 days after primary repair, magnetic resonance imaging was used for
      evaluation, correlating precisely with the surgical pathology. This non-invasive
      tool can be very helpful in the early post-operative period when active flexion
      is not possible to aid in the clinical diagnosis of tendon rupture.

PMID- 7561401
TI  - Early active mobilization of tendon grafts using mesh reinforced suture
      techniques.
AB  - The flexor digitorum profundus tendon in 11 digits with division of both flexor
      tendons in zone 2 was reconstructed with a palmaris longus tendon graft in a two
      stage procedure. The distal and proximal fixation of the graft was reinforced
      with a polyester mesh sleeve placed around the ends of the graft during stage 1.
      All digits were mobilized with a combination of active extension and active and
      passive flexion within 3 days of the second stage. There were three ruptures, one
      due to faulty technique and two due to falls on outstretched hands during alcohol
      intoxication and football. Excluding the ruptures, the mean active composite
      distal and proximal interphalangeal joint range of motion 6 weeks and 6 months
      post-operatively was 141 degrees and 136 degrees respectively. The results
      indicate that palmaris longus tendon grafts can survive and heal during early
      active mobilization, with few or no adhesions of functional significance. The
      techniques described here represent one possible approach to the safe
      implementation of early active mobilization after tendon grafting procedures.

PMID- 7561400
TI  - Early active mobilization after tendon transfers using mesh reinforced suture
      techniques.
AB  - 23 tendon transfers in the hand and forearm were performed using a polyester mesh
      sleeve to reinforce conventional suture techniques. All transfers were mobilized
      with active flexion and extension within 3 days of operation. Excluding one
      rupture (due to extreme unintentional loading) and depending on the type of
      transfer used, a mean of between 69% and 78% of the final active range of motion
      was obtained 1 month post-operatively. With the exception of transfers for wrist
      extension, the mean final active range of motion amounted to between 91% and 100%
      of the available passive range of motion and between 75% and 100% of the
      corresponding "normal" active range of motion in the opposite hand. The mean
      final active range of motion after reconstructions for wrist extension amounted
      to 85% of the passive range of motion and to at least 80% of the maximum range of
      motion potentially available with the transfers used. The results indicate that
      early active mobilization after tendon transfers may offer significant advantages
      in terms of quicker and simpler rehabilitation as well as improved results.

PMID- 7561402
TI  - Temporary use of a silicone rod in a case of infection resulting from tendon
      surgery.
AB  - A patient was treated by tendon grafting following division of both flexor
      tendons of a digit. The graft was removed because of infection and a silicone rod
      was inserted in spite of the suppuration. After the replacement of the implant by
      a new tendon graft, the final result was satisfactory and the patient recovered
      good function.

PMID- 7561403
TI  - Work of flexion after tendon repair with various suture methods. A human
      cadaveric study.
AB  - After flexor tendon repair there is often increased resistance to tendon gliding
      at the repair site, which is greater for techniques using increased suture
      strands or suture material. This increased "friction" may be measured as the
      "work of flexion" in the laboratory setting. Tendon repairs performed in zone 2
      in human cadaver hands using the two strand Kessler, the lateral Becker, the six
      strand Savage, internal and dorsal tendon splint, or the external mesh sleeve
      techniques, had "work of flexion" measurements made both before and after the
      laceration and repair. The average increase in work of flexion was 4.8% for
      Kessler; 6.5% for Becker; 10.9% for Savage; 19.3% for the internal tendon splint,
      16.2% for the dorsal tendon splint and 44.3% for the external mesh sleeve. The
      work of flexion was found to increase in direct proportion to the amount of
      suture material at the repair site.

PMID- 7561405
TI  - Intra-uterine and juxtanatal repair of syndactyly in foetal mice.
AB  - 39 foetal mice with genetic syndactyly were identified in utero at 17 days of
      gestation, and the right hindfoot extruded through the uterus. The syndactylous
      digits were separated by simple incisions. In one group (n = 25) digit separation
      was maintained during wound healing by the interdigital application of a silver
      microclip. Digit separation was also assessed in a second group of newborn mice
      less than 24 hours old (juxtanatal population, n = 24). Two foetuses (5%) and six
      newborns (25%) developed digital necrosis following microclip application. In the
      remaining microclipped animals (23 intrauterine and 10 juxtanatal), microclip
      application maintained digit separation, allowing wound healing to occur with
      epithelialization of the separated digits. No inflammation or scar formation
      occurred. In the third group (n = 22) without microclip application, the digital
      skin reapproximated and webbing recurred during wound healing. These studies
      demonstrate the need to maintain digit separation during wound healing following
      intra-uterine or juxtanatal syndactyly repair.

PMID- 7561404
TI  - The in vivo response of foetal tendons to sutures.
AB  - The in vivo response of foetal flexor digitorum profundus tendons to tendon
      sutures was studied macroscopically and microscopically in foetal lambs. No
      tendon adhesions were noted at any of the examination intervals. 4 days after
      injury, a mild inflammatory reaction was noted around the suture. The tendon
      examined at the 4-week interval showed evidence of migration of epitenon cells
      from the outer surface of the tendon into the suture track. The tendon examined
      at the 6-week interval showed normal tendon fibres surrounding the suture site.
      Differences between foetal skin and foetal tendon healing are discussed along
      with the possible role of amniotic fluid in modulating the healing process in the
      foetus.

PMID- 7561406
TI  - Tissue expansion for Apert's syndactyly.
AB  - Tissue expansion is useful in post-traumatic reconstruction in the upper
      extremity. Its use has also been proposed in congenital syndactyly. Expanded
      local skin flaps would in theory provide locally appropriate cover, obviating the
      need for skin grafts. We report a retrospective assessment of tissue expansion in
      the management of Apert's syndactyly. Despite theoretical benefits, tissue
      expansion significantly increased the required number of operations. The
      technique was associated with an unacceptable rate of complications, and
      generated inadequate skin flaps, and web spaces requiring a higher rate of
      revision than traditional techniques. Despite expectations, tissue expansion for
      Apert's syndactyly proved disappointing and is not advocated.

PMID- 7561407
TI  - Familial congenital pseudarthrosis of the ulna.
AB  - A mother and daughter, both presented with congenital pseudarthrosis of the ulna
      due to neurofibromatosis. The daughter is one of identical twins, the second twin
      not having a pseudarthrosis. The mother's uncle also had pseudarthrosis of the
      tibia. This suggests a complex variable genetic inheritance pattern for
      pseudarthrosis in neurofibromatosis. Despite having had no treatment, the mother
      had minimal symptoms, minimal deformity, and no radial head dislocation.

PMID- 7561409
TI  - Surgical correction of pseudo-ainhum in Vohwinkel syndrome.
AB  - Vohwinkel syndrome or hereditary mutilating keratodermatitis is a rare condition
      producing palmoplantar hyperkeratosis and constricting rings of the fingers and
      toes which can progress to compromise neurovascular function and mobility.
      Medical treatment with oral retinol derivatives is recommended when its use is
      not contra-indicated. This paper describes surgical correction of the
      constricting rings on both hands in a 33-year-old woman affected by this
      condition.

PMID- 7561410
TI  - Congenital perforations of the triangular fibrocartilage of the wrist.
AB  - A cadaveric study of the triangular fibrocartilage of the wrist in the foetus and
      infant revealed a high incidence of congenital perforation. In the second half of
      the study, wrist arthrography in foetal and infant cadavers with crown-rump
      length of more than 20 cm followed by dissection of the wrist joints showed good
      correlation between the two. In 60 cadavers there were 11 with bilateral
      perforations and five had unilateral perforation. This gave a total of 27
      perforations in 120 wrist joints studied.

PMID- 7561408
TI  - The use of a bilobed flap in the correction of radial club hand.
AB  - A new incision is described for the correction of radial club hand. By the use of
      a bilobed flap, redundant skin is transferred from the ulnar side of the wrist to
      the radial side, where there is tension as the wrist becomes straight. The flap
      has been shown to be safe and effective in six consecutive cases, and access to
      the wrist and surrounding soft tissue structures is excellent.

PMID- 7561412
TI  - Children's proximal phalangeal neck fractures with 180 degrees rotational
      deformity.
AB  - Five patients under 4 years of age with 180 degrees rotational deformity of a
      proximal phalangeal neck fracture are described. All cases resulted from a direct
      shear force to the bone coupled with a sharp withdrawal reaction of the hand. All
      of the children were successfully treated with open reduction and internal
      fixation but only after fruitless attempts at closed manipulation and an initial
      lack of recognition of the severity of the fracture. Each child achieved a full
      functional recovery of the finger with clinical and radiological union at 4
      weeks.

PMID- 7561411
TI  - Scapho-trapezoid arthritis. A cause of residual pain after arthroplasty of the
      trapezio-metacarpal joint.
AB  - Scapho-trapezoid osteoarthritis may accompany osteoarthritis of the CM joint of
      the thumb. If the scapho-trapezoid joint is not excised when performing an
      excision of the trapezium with ligament reconstruction and interposition of the
      tendon of the FCR, the procedure may be unsuccessful. We describe three patients
      with four thumbs in which scapho-trapezoid osteoarthritis was associated with
      basal joint arthritis. In one patient, it was not recognized pre-operatively and
      persistent post-operative pain dictated further surgery. In the other patients,
      the scapho-trapezoid joint was excised primarily, with resolution of the pain. In
      the pre-operative assessment, the scapho-trapezoid joint should be carefully
      studied to prevent failure of the procedure.

PMID- 7561413
TI  - Fractures of the distal radius and ulna.
AB  - Associated fractures of the distal ulnar metaphysis were present in 19 of 320
      distal radial fractures requiring either closed manipulation or surgical
      treatment over a 2-year period. Four morphological patterns of ulnar fracture
      were encountered, the commonest being the type 1 simple extra-articular fracture
      of the distal end of ulna with minimal comminution (eight out of 19). 15 patients
      were treated conservatively and two each were treated by internal and external
      fixation. 15 patients were reviewed after a mean follow-up of 23.8 months and
      there were four excellent, five good, five fair clinical results and one poor
      result. Radiographically the distal radio-ulnar joint (DRUJ) was normal in eight
      wrists, but longitudinal or horizontal disruption of the DRUJ was present in
      seven wrists. Fracture callus encroached on the DRUJ in three patients, who also
      had limitation of forearm rotation. Two comminuted ulnar fractures (type 4)
      developed non-union, but both patients had full forearm rotation, in contrast to
      restriction of forearm rotation in four out of five patients with type 1
      fractures.

PMID- 7561414
TI  - Pins and plaster vs external fixation in the treatment of unstable distal radial
      fractures. A randomized prospective study.
AB  - 90 unstable fractures of the distal radius were studied in a randomized,
      prospective manner. Follow-up consisted of patient questionnaire, medical record
      review, therapist evaluation and radiography at 4 months, 1 year and 2 years post
      operatively. Overall results were good or excellent in 94%. No significant
      differences were found between treatment groups (external fixation and pins and
      plaster) in final results, range of motion, intrinsic tightness, grip strength,
      or the presence of arthritis. The complication rate was high for both groups
      (45%), and half of the complications were major. External fixation maintained
      radial length more effectively (significantly in those patients followed for 2
      years) but was associated with higher initial costs (20 times) and a greater
      number of minor complications.

PMID- 7561415
TI  - Repeat Russe bone grafting after failed bone graft surgery for scaphoid non
      union.
AB  - We report the long-term outcome of repeat Russe bone grafting after failure of a
      previous Russe graft for scaphoid non-union. 15 patients were followed for a mean
      of 71 months after their last surgical procedure. 11 patients had undergone a
      single previous Russe graft and four patients had two previous graft attempts.
      Internal fixation was used in only three patients. Eight out of 15 (53%) patients
      achieved union after a single repeat graft and one out of four united after a
      third attempt. When union was achieved, range of motion was unchanged, grip
      strength was increased 10% and pain was slight to none, allowing return to full
      employment in seven out of the nine patients. All patients who did not achieve
      union have either undergone a salvage procedure or are contemplating one. Based
      on the literature and our relatively low rate of union without internal fixation
      (53%), we recommmend supplementary internal fixation if repeat Russe bone
      grafting is undertaken. When union is achieved, satisfactory results can be
      expected.

PMID- 7561416
TI  - Influence of joint laxity on scaphoid kinematics.
AB  - Excessively lax wrists more frequently become symptomatic if overloaded or
      injured than normal joints. Whether this is the consequence of biological or
      mechanical factors or both remains unknown. This study evaluates the relationship
      between the degree of joint laxity and scaphoid kinematic behaviour during radio
      ulnar deviation of the wrist in 60 normal volunteers. There is a significant
      linear relationship between the direction of scaphoid rotation and the amount of
      wrist joint laxity. During lateral deviation of the wrist, joints that are more
      lax have a scaphoid rotating mainly along the sagittal plane of flexion and
      extension, with little lateral deviation. In contrast, the scaphoid of volunteers
      with decreased laxity rotate mostly along the frontal plane of radioulnar
      deviation with minimal flexion extension. These results support the concept of
      increased out-of-plane scaphoid rotation as a factor of increased vulnerability
      during over-work or injury.

PMID- 7561417
TI  - Treatment of hyperextension injuries to the PIP joint.
AB  - A prospective randomized trial of type 1 hyperextension injuries to the PIP joint
      treated conservatively by an elastic double-finger bandage or an aluminium splint
      for 2 weeks showed no differences in the clinical outcome after 6 months.

PMID- 7561418
TI  - The treatment of chronic flexion contractures of the proximal interphalangeal
      joint.
AB  - A method of treatment of chronic flexion contractures of the PIP joint is
      presented, with the results obtained in 19 patients treated between 1989 and 1992
      after a follow-up of from 6 to 53 months. The flexion contractures, with an
      extension deficit which ranged between 70 and 90 degrees, had been present for a
      period of between 2 months and 24 years. Our treatment program involves the
      surgical release of the unreducible PIP joint followed by the use of static
      and/or dynamic splints. Surgery is performed using a midlateral approach; the
      accessory collateral ligament and the flexor sheath are incised and, after the
      volar plate and check-rein ligaments have been excised, forced hyperextension is
      applied. The main collateral ligaments are carefully spared and freed from the
      condyle if there are any remaining adhesions. In our 19 patients, complete
      extension of the finger was achieved in 11 cases (57.9%); in the remaining 8
      cases (42.1%) the residual extension deficit ranges from 10 to 15 degrees. In our
      experience this combined surgical and rehabilitative approach had led to
      consistently good results with minimal complications.

PMID- 7561420
TI  - The by-pass extensor tendon transfer. A salvage technique for loss of substance
      of the extensor apparatus in long fingers.
AB  - A salvage technique for the treatment of substance loss of the extensor apparatus
      with some special features is presented. It uses the extensor indicis muscle
      prolonged with a tendon graft. The tendon is directly attached to the middle
      phalanx. After surgery, the wrist is immobilized in extension, allowing immediate
      active mobilization of the PIP joint. The results in five patients are
      satisfactory.

PMID- 7561419
TI  - Combined central slip and volar plate injuries at the PIP joint.
AB  - PIP joint injuries are common. We describe an unusual injury in which an apparent
      volar plate avulsion injury was associated with a dorsal, central slip avulsion
      fracture. We postulate that the mechanism of injury would appear to have been
      forced flexion with the central slip being avulsed and the volar plate fracture
      occurring as a secondary impingement fracture. Our two cases were treated with
      full extension splinting with satisfactory results.

PMID- 7561421
TI  - Post-traumatic triggering of extensor pollicis longus at the dorsal radial
      tubercle.
AB  - A case of post-traumatic triggering of the tendon of extensor pollicis longus
      around Lister's tubercle is described. This condition was successfully treated by
      surgical release.

PMID- 7561422
TI  - Idiopathic avascular necrosis of the capitate.
AB  - Idiopathic avascular necrosis (AVN) of the capitate is rare. A 44-year-old woman
      presented with chronic pain in her dominant wrist without a history of trauma.
      Clinical and standard radiological examination were initially inconclusive, while
      MRI was diagnostic. Mid-carpal arthrodesis gave a satisfactory short term result,
      and the long term result is awaited. Idiopathic AVN of the capitate should be
      included in the differential diagnosis of chronic wrist pain.

PMID- 7561424
TI  - Extradigital glomus tumour.
AB  - We report a case of an extradigital glomus tumour found in the forearm. A review
      of the literature suggests that extradigital glomus lesions in the upper limb may
      be more common than they are thought to be.

PMID- 7561423
TI  - The carpal boss. A 20-year review of operative management.
AB  - Between 1969 and 1989, 116 patients were evaluated and treated surgically for
      symptomatic carpal boss. Their mean age was 32 years and male and female patients
      were equally affected. 28 patients gave a history of previous injury. Surgical
      treatment consisted of excision of the localized bony abnormality and the
      associated degenerative arthritic process to the level of normal articular
      surfaces and normal adjacent cancellous bone. The mean follow-up period for the
      patients in this study was 42 months. Complete symptomatic relief was observed in
      94% of the patients undergoing surgical treatment. Recurrence or persistence of
      symptoms developed in seven surgical patients. Six had a second operation with
      more extensive removal of sclerotic bone and degenerate cartilage, and all
      patients had relief of symptoms.

PMID- 7561425
TI  - Upper arm tourniquet pain in local anaesthetic surgery.
AB  - A prospective study was performed on 100 consecutive patients (110 procedures) of
      the perception of pain from an arm tourniquet during a local anaesthetic
      procedure. This was assessed subjectively, and objectively using a visual
      analogue scale. For tourniquet times up to 20 minutes, the tourniquet was well
      tolerated with only one failure (1% of patients) and all successful patients
      stated that they would be happy to have a similar procedure again. Unlike
      previous studies, there appeared to be no correlation between time of tourniquet
      use and the pain perceived. Rather, there appeared to be an idiosyncratic
      response to the tourniquet which was borne out by the ten patients who had
      bilateral procedures at least 6 weeks apart and showed consistently repeatable
      scores.

PMID- 7561426
TI  - Patients with suspected carpal tunnel syndrome should undergo pre-operative nerve
      conduction studies.

PMID- 7561429
TI  - Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium
      (CHRPE) in patients with sporadic colorectal carcinoma.
AB  - In order to investigate the frequency of congenital hypertrophy of the retinal
      pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was
      carried out in 34 patients with colorectal carcinoma without known familial
      disposition. CHRPE is one of the most frequent extracolonic manifestations in
      familial adenomatous polyposis. None of the patients showed any sign of CHRPE. It
      is concluded that although genetic factors are presumably of importance in the
      development of sporadic colorectal cancer, CHRPE cannot be used as a marker for
      future risk of colorectal carcinoma except in polyposis families.

PMID- 7561428
TI  - Potential disadvantages of post-operative adjuvant radiotherapy after anterior
      resection for rectal cancer: a pilot study of sphincter function, rectal capacity
      and clinical outcome.
AB  - The aim of this study was to try to gauge the functional effect of post-operative
      adjuvant radiotherapy after potentially curative anterior resection for carcinoma
      of the rectum. Anorectal function was studied both in the laboratory and
      clinically in 59 patients, a median of 12 months (range 6-96) after operation.
      Nine patients received post-operative radiotherapy and 50 matched patients were
      treated by surgery alone. Though maximum resting anal pressures and maximum
      squeeze pressures were similar in the two groups of patients, the length and
      pressure profile of the anal sphincter were both markedly abnormal after
      radiotherapy. The capacity and compliance of the neorectum were diminished
      significantly after radiotherapy (maximum tolerated volume 53 ml vs 110 ml after
      surgery alone, P = 0.008, compliance 1.5 ml/cm H2O vs 3.7 ml/cm H2O after surgery
      alone, p = 0.018) and the amount of distension of the neorectum required to
      produced maximum inhibition of the anal sphincter during the rectoanal inhibitory
      reflex was also significantly diminished after radiotherapy (P = 0.005). Clinical
      anorectal function was worse among patients who had received radiotherapy, a
      greater proportion of whom experienced both urgency of defaecation and varying
      degrees of incontinence. Major faecal leakage necessitating the use of a pad was
      recorded in 3 of the 59 patients after radiotherapy (one of whom required a
      permanent colostomy), but in only 5 of 50 patients after surgery alone.

PMID- 7561427
TI  - Analysis of local recurrence rates after surgery alone for rectal cancer.
AB  - Local recurrence (LR) continues to be a major problem following surgical
      treatment for rectal cancer, and proposed ways of reducing this remain
      controversial. The aim of this study was to review results from published
      surgical series in which adjuvant therapies were not used. A Medline search
      identified series published between January 1982 and December 1992 with follow-up
      on at least 50 patients with rectal cancer treated surgically for cure, without
      adjuvant therapy. Fifty one papers reported follow-up on 10,465 patients with a
      median LR rate of 18.5%. LR was 8.5%, 16.3% and 28.6% in Dukes' A, B and C
      patients respectively, 16.2% following anterior resection and 19.3% following
      abdominoperineal resection. Nine papers (1,176 patients) reported LR rates of 10%
      or less. LR was 7.1% in 1,033 patients having total mesorectal excision and 12.4%
      in 476 patients having extended pelvic lymphadenectomy. Routine cytocidal stump
      washout in 1,364 patients was associated with 12.2% LR, however a higher
      proportion (41%) also underwent total mesorectal excision. In 52% of cases, LR
      was reported to have occurred with no evidence of disseminated disease. Surgical
      technique is an important determinant of LR risk. LR rates of 10% or less can be
      achieved with surgery alone in expert hands.

PMID- 7561430
TI  - Accuracy of colonoscopy in localisation of colorectal cancer.
AB  - An audit was performed of 77 patients with a single colorectal cancer visualised
      and sited before surgery by colonoscopic examination. The site of the cancer
      described at colonoscopy was compared with the actual site found at laparotomy.
      Six significant errors in preoperative localisation were encountered, when a
      change from the preoperatively planned resection to an alternative resection was
      found necessary. In two of these cases, extra morbidity was encountered as a
      result of these siting errors. Inaccurate localisation is a potential hazard of
      colonoscopy, especially when the examination is incomplete.

PMID- 7561431
TI  - Stapled ileal pouch-anal anastomosis with resection of the anal transition zone.
AB  - We assessed the outcome of stapled ileal J-pouch-anal anastomosis with
      intersphincteric resection of the anal transition zone in 83 consecutive patients
      with ulcerative colitis (n = 71) or familial adenomatous polyposis (n = 12).
      There was no postoperative mortality. Two patients (2.4%) required permanent
      ileostomy for manifestation of unsuspected Crohn's disease. Major postoperative
      complications consisted of pelvic sepsis, anastomotic leakage, and pancreatitis
      with 3.6% each. Both, frequency of bowel movements and degree of continence
      improved with time. Two years after takedown of the diverting ileostomy 45
      patients with ulcerative colitis and 12 with familial adenomatous polyposis were
      assessed with a frequency of bowel movements of 5.6 +/- 2 and 3.2 +/- 1 per 24 h,
      respectively (P < 0.05). At this time none of them had major daytime or nighttime
      incontinence. Minor incontinence was reported by 9% and 14% of the patients with
      ulcerative colitis during day-time and night-time, respectively. The patients
      with familial adenomatous polyposis demonstrated better results, without day-time
      seepage and intermittent nocturnal seepage in only 9%. It is concluded that
      direct ileal J-pouch-anal anastomosis is a safe procedure with excellent
      functional results for patients with ulcerative colitis and familial adenomatous
      polyposis.

PMID- 7561432
TI  - Anal and rectal motility responses to distension of the urinary bladder in man.
AB  - Recto-anal motility response to bladder distension was studied under general
      anaesthesia in 12 patients undergoing intestinal resection for Crohn's disease of
      the small intestine or colonic cancer. The effect of epidural anaesthesia on anal
      tone and on the motility response to bladder distension was studied in six of
      these patients. An anal pressure increase on bladder distension was observed in
      all individuals. No motility response was noted in the rectum. The anal pressure
      response to bladder distension was abolished by epidural anaesthesia. It was
      concluded that anal pressure in man under general anaesthesia was tonically
      influenced by the thoracolumbar sympathetic outflow. An excitatory vesico-anal
      reflex was demonstrated. It appears as this reflex is mediated via the spinal
      cord.

PMID- 7561433
TI  - Relationship of symptoms in faecal incontinence to specific sphincter
      abnormalities.
AB  - We aimed to determine if the type of clinical presentation in patients with
      faecal incontinence correlated with the underlying sphincter pathology. One
      hundred fifty one consecutive patients (129 female) with faecal incontinence were
      classified as having either passive (faecal incontinence without the patient's
      knowledge) or urge incontinence (incontinence occurring with the patient's
      awareness, against their will because of lack of voluntary control), and were
      investigated by routine anorectal physiological testing and anal endosonography.
      Sixty six patients had passive incontinence (PI) only, 42 patients had urge
      incontinence (UI) only, 38 patients had combined passive and urge incontinence,
      and 5 patients had soiling after defaecation only. Patients with PI alone (n =
      66) were significantly older than those with UI alone (PI vs UI, 60 vs 42 yr, p <
      0.001), had a lower maximum resting anal pressure (51 vs 64 cm H2O, means, p =
      0.02) and had a significantly (p < 0.001) greater prevalence of internal anal
      sphincter (IAS) defects. Patients with UI alone (n = 42) had a significantly
      lower maximum voluntary contraction pressure (PI v UI, 72 v 42 cm H2O, p <
      0.001), and a significantly (p < 0.001) greater prevalence of external anal
      sphincter (EAS) defects. The clinical classification of faecal incontinence into
      passive and urge incontinence relates to specific patterns of abnormality of the
      internal and external anal sphincters.

PMID- 7561434
TI  - Adult Hirschsprung's disease. Results of the Duhamel's procedure.
AB  - Eleven patients with adult Hirschsprung's disease were treated at Seoul National
      University Hospital (SNUH, 8 cases) and Chosun University Hospital (CUH, 3 cases)
      between 1985 and 1992. Of the 11 patients, seven were male. The age of the
      patients ranged from 11 to 30 years, and all presented with chronic constipation
      and recurrent faecal impactions that required periodic enemas and laxatives. The
      Duhamel's operation, as a single or staged procedure, was performed in all
      patients. Levels of aganglionosis in 9 patients were confined to the rectosigmoid
      colon (82%). There were three major post-operative complications. Two patients
      developed fistula-in-ano at the anastomotic site, and one patient developed
      ileus. However, these complications resolved with conservative management. The
      longterm results were excellent except for one patient who developed impotence.
      The mean frequency of bowel movements was usually once or twice a day without the
      aid of other treatments. Our results indicate that Duhamel's operation is a
      highly acceptable procedure in the management of adult Hirschsprung's disease.

PMID- 7561436
TI  - The first twenty operations for rectal cancer.

PMID- 7561435
TI  - Bacteriology and complications of chronic pilonidal sinus treated with excision
      and primary suture.
AB  - Two prospective studies were undertaken to examine the role of bacteria in the
      outcome after excision and primary suture for chronic pilonidal sinus disease. In
      the first study 52 consecutive patients were given cloxacillin as prophylaxis. In
      a second randomised study 51 patients were given 2 g cefoxitin intravenously (n =
      25) or no prophylaxis (n = 26). From 49 out of 98 patients (50%) no
      microorganisms were isolated from sinuses preoperatively. Wound complications
      were observed postoperatively in 61% of the patients (63/103). A postoperative
      bacteriology sample was positive in 47 of 49 samples (96%). Preoperative presence
      of bacteria was not significantly associated with wound complications. Anaerobe
      isolates were present in 40% of patients preoperatively whereas aerobes were
      cultured in 43% postoperatively. After an observation period of 30-42 months,
      recurrences were 13% among the patients (7/52) who had been given cloxacillin. No
      recurrences were seen in the last study after an observation period of 18-30
      months, for an overall 7% in both studies. We conclude that preoperative
      bacterial isolates, usually anaerobes, in chronic pilonidal sinuses do not
      influence the complication rate since bacterial isolates from infected wounds are
      mostly aerobes.

PMID- 7561437
TI  - Giant diverticulum of the sigmoid colon.
AB  - While diverticulosis of the colon is a relatively common disease, a solitary
      giant diverticulum (GD) of the sigmoid is rare. Although there exist some
      theories about the formation of a GD, none is really conclusive. Symptoms are
      similar to diverticular disease, and diagnosis is easy with the aid of radiology.
      Early surgical treatment is necessary since the complication rate is high (19%).

PMID- 7561439
TI  - A case of pneumatosis coli managed by restorative proctectomy and ileal pouch
      anal anastomosis.
AB  - Pneumatosis coli is a rare condition in which gas filled cysts occur in the wall
      of the intestines. Most symptomatic patients can be managed conservatively but
      those who fail medical management or who develop bowel obstruction will require
      surgery. Surgery usually involves a limited colectomy with a potential for
      recurrence. We describe a case of pneumatosis coli managed successfully by
      restorative proctocolectomy and ileal pouch-anal anastomosis.

PMID- 7561438
TI  - Human colonic motility: physiological aspects.
AB  - From the point of view of its motor activity, the human colon is probably the
      least understood of the abdominal hollow viscera. This is due to several facts:
      a) its proximal portions are relatively inaccessible due to anatomical reasons;
      b) there is no reliable animal model due to the considerable anatomic
      physiological differences among mammals. For instance, most deductions about
      human colonic motor activity have been drawn from experiences in cats and dogs,
      in which the colon displays a cecum which is almost atrophic, and the viscus is
      featureless and C-shaped, without the haustrations and the sharp angulations seen
      in man, c) the wide fluctuations of motility in the daily time course of the same
      individual makes the interpretation of many studies difficult, especially
      considering the fact that, until recently, most of the studies on human colonic
      motility have been conducted for relatively short (30-180 min) recording periods.
      Recently, however, techniques that allow recording from the proximal portions of
      the human colon have been developed, and prolonged (24 h or more) observations of
      myoelectrical and contractile events have been achieved, thus improving our
      knowledge of the normal physiologic properties of the viscus. These informations
      have furthermore been integrated and confirmed by scintigraphic techniques (less
      invasive), that allow the measurement of intracolonic flow activity. The purpose
      of the present paper is to review the physiological aspects of colonic motility
      in man, quoting animal studies where human ones are lacking. We will briefly
      introduce some basic concepts, then a more detailed description of the main topic
      will follow.

PMID- 7561441
TI  - Genetic factors in the development of diabetic nephropathy.

PMID- 7561440
TI  - Fc gamma receptors of phagocytes.

PMID- 7561442
TI  - Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B:
      observations with three preparations from different geographic sites.
AB  - It has been suggested that herbs of the Phyllanthus family may have antiviral
      activity. We therefore tested the effects of three different Phyllanthus extracts
      on the serologic status of 123 patients with chronic hepatitis B. Eleven patients
      received an extract of Phyllanthus amarus (L) provided by S.P. Thyagarajan,
      Madras, India. Forty-two patients received Phyllanthus niruri (L), gathered from
      Hainan Province in China, and 35 patients received an extract of Phyllanthus
      urinaria (L), which had been gathered in Henan Province. Thirty-five control
      patients received no herbal therapy. The patients receiving Phyllanthus urinaria
      (L) were both more likely to lose detectable hepatitis B e-antigen from their
      serum and more likely to seroconvert hepatitis B e-antibody status from negative
      to positive than were patients given either of the other two preparations. No
      patient changed status with respect to hepatitis B s-antigen.

PMID- 7561443
TI  - The plasma dilution factor: predicting how concentrations in plasma and serum are
      affected by blood volume variations and blood loss.
AB  - To determine the effects of therapeutic interventions on plasma protein
      concentrations, it is often desirable to rule out nonspecific effects of
      hemodilution. Because red cells are restricted to the vascular space, the
      hematocrit (Hct) is a convenient marker. At the bedside--and even in scientific
      reports--a simple ratio of Hcts (obtained before and after the change in plasma
      volume) is often used to "correct" the value of interest. This is incorrect, and
      it may introduce a sizeable error. A new method, the plasma dilution factor
      (PDF), has been mathematically deduced. It accounts for the influence of any
      blood loss, plasma osmolality changes, and blood volume variations on plasma and
      serum concentrations. In an in vitro experiment, blood loss and osmolality and
      blood volume changes were simulated through the withdrawal of various volumes of
      blood, which were replaced with smaller, identical, or larger volumes of
      hypotonic, isotonic, or hypertonic solutions. The PDF accurately predicted
      changes in concentrations of albumin, fibrinogen, and antithrombin III. In
      contrast, the Hct ratio significantly underestimated the effects of dilution. Von
      Willebrand factor concentrations after hemodilution through dextran infusion in
      volunteers were the same as predicted by the PDF. In patients undergoing
      orthopedic surgery who were also given dextran, the postdilution von Willebrand
      factor concentrations were higher than predicted by the PDF. The Hct gave a false
      impression of a decrease in the volunteers that was not explained by
      hemodilution, and it failed to detect the von Willebrand factor response to
      trauma in the surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561445
TI  - Siggaard-Andersen algorithm-derived p50 parameters: perturbation by abnormal
      hemoglobin-oxygen affinity and acid-base disturbances.
AB  - The p50 and derived indexes, calculated by using the Siggaard-Andersen algorithm
      from a single measurement of arterial blood gas tensions and hemoglobin-oxygen
      saturation, are used to assess tissue oxygen availability in critical illness. We
      tested the accuracy of the Siggaard-Andersen p50 algorithm over a wide range of
      pathophysiologic conditions. Blood gases, cooximetry, and calculation of standard
      and in vivo p50 were performed at multiple saturations, CO2 tensions, and H+
      concentrations on blood with normal (standard p50 of 26.1 and 26.7 mm Hg),
      increased (19.0 and 25.4), and reduced (33.9 and 38.2) hemoglobin-oxygen
      affinity, as well as on high-affinity blood from two patients with diabetic
      ketoacidosis (16.7 and 20.8). Log p50 in vivo/pH plots were constructed to
      determine the Bohr effect. Except in the normal affinity specimens (coefficient
      of variation < 1.7%), standard p50 values showed high variability (coefficient of
      variation > 5.9%), with saturation-linked bias and distortion of the Bohr effect.
      Standard p50 was overestimated by up to 11 mm Hg as saturation approached 97%.
      Although base deficit correction of the stored specimens (6.9 < pH < 7.1)
      restored the Bohr effect and improved the accuracy of standard p50 calculations
      (coefficient of variation = 4.4% and 2.9%), saturation-linked bias persisted. We
      conclude that Siggaard-Andersen p50 calculations may be misleading when there are
      disturbances of hemoglobin-oxygen affinity and acid-base balance, owing to
      changes in shape of the hemoglobin-dissociation curve. When metabolic acidosis
      occurs with high hemoglobin-oxygen affinity, as can occur in critical illness,
      indexes derived by the Siggaard-Andersen algorithm on arterial blood may greatly
      overestimate oxygen availability.

PMID- 7561444
TI  - Monocyte chemoattractant activity associated with human colon mucosal cells.
AB  - Mucosal epithelial cell preparations from 18 disease-free segments of human colon
      resections and 7 cell lines were examined for chemoattractant properties. Mucosal
      cells were dissociated from lamina propria by sequential incubations in
      ethylenediaminetetraacetic acid, harvested at 1.5 x 10(6) cells/ml, and lysed.
      Lysates were tested for chemoattractant activity for monocytes and neutrophils.
      Chemoattractant preparations were further purified by gel filtration
      chromatography, and amino acid analysis was performed on selected chemoattractant
      fractions. Mucosa from normal bowel exhibited significant chemoattractant
      properties for monocytes, up to 15 times greater than for neutrophils.
      Checkerboard analysis indicated chemotaxis rather than chemokinesis. Neither cell
      culture nor lamina propria cell lysates exhibited statistically significant
      chemoattraction, although activity was evident in certain preparations of
      isolated cell cultures. Chromatography of human mucosal chemoattractant
      preparations consistently gave peaks of activity in the 2000 dalton range. These
      yielded consistent amino acid profiles, with aspartic acid, glutamic acid,
      glycine, alanine, and lysine being dominant in all preparations. This peptide is
      apparently different from other known chemotactic agents and could play a role in
      recruitment of mononuclear phagocytes to the mucosa of the human colon.

PMID- 7561446
TI  - Protein C deficiency in Kuwait.

PMID- 7561447
TI  - Endothelial cell injury induced by plasmin in vitro.
AB  - We investigated the effect of plasmin on the integrity and function of
      endothelial cells to elucidate the mechanism by which bleeding or rethrombosis
      may be induced in thrombolytic therapy. When incubated with cultured human
      umbilical vein endothelial cells (HUVECs), plasmin increased the endothelial
      permeability to serum albumin 10 minutes after the incubation. Plasmin damaged
      the cell membranes 30 minutes after the incubation, detached the cells from the
      matrix 3 hours after the incubation, and finally induced cell lysis. Such
      damaging effects on HUVECs were not observed with plasminogen or plasmin
      pretreated with aprotinin and alpha 2-plasmin inhibitor, suggesting that the
      catalytic function of plasmin plays an important role in inducing this damage.
      Sulfur 35-labeled glycosaminoglycans (35S-GAGs) of HUVECs were decreased 1 hour
      after the incubation of plasmin with HUVECs, and the thrombomodulin (TM) activity
      of HUVECs measured by protein C activation capacity was decreased 6 hours after
      the incubation. Neither 35S-GAGs nor the TM activity of HUVECs was decreased
      after the incubation of plasmin pretreated with aprotinin and alpha 2-plasmin
      inhibitor. These findings suggest that the nonthrombogenic properties of
      endothelial cells can be damaged by the proteolytic action of plasmin. Our
      findings, taken together, suggest that plasmin damages the endothelial barrier
      function, endothelial cell integrity, and nonthrombogenic properties. These
      damaging effects of plasmin on endothelial cells may be related to the
      pathophysiology of bleeding or rethrombosis observed in patients undergoing high
      dose thrombolytic therapy for thrombosis.

PMID- 7561448
TI  - Estradiol inhibits mesangial cell-mediated oxidation of low-density lipoprotein.
AB  - It has been suggested that hyperlipidemia may contribute to the progression of
      renal disease via the deleterious effects of oxidized low-density lipoprotein
      (LDL) on the glomerular mesangium. Because estrogens possess potent antioxidant
      activity, we sought to determine whether sex hormones influence the oxidation of
      LDL by mesangial cells. Rat mesangial cells were incubated with LDL (200
      micrograms/ml), and the extent of lipid oxidation was assessed by the generation
      of thiobarbituric acid reactive substances (TBARS), by increased electrophoretic
      mobility, and by enhanced uptake of mesangial cell-modified LDL by macrophages. A
      progressive rise in TBARS and an increase in electrophoretic mobility was
      observed on incubation of LDL with mesangial cells. Coincubation with estradiol
      (10 mumol/L) reduced TBARS generation by 46% at 36 hours (p < 0.01) and reversed
      the increase in relative electrophoretic mobility (1.25 +/- 0.07 vs 1.01 +/-
      0.03, p < 0.05). LDL that had been oxidized by mesangial cells in the presence of
      estradiol (10 mumol/L) showed reduced uptake by macrophages when compared with
      LDL that had been oxidized by mesangial cells in the absence of estradiol (14 +/-
      2 pmol/10(6) cells per hour vs 22 +/- 3 pmol/10(6) cells per hour, p < 0.05). In
      contrast, neither testosterone nor estrone had any effect on these parameters. We
      conclude that estradiol, by virtue of its antioxidant properties, inhibits
      mesangial cell-mediated oxidation of LDL and reduces the uptake of mesangial cell
      modified LDL by macrophages.

PMID- 7561449
TI  - Soluble complement receptor 1 inhibits both complement and granulocyte activation
      during ex vivo hemodialysis.
AB  - Hemodialysis with cellulosic membranes results in both complement and granulocyte
      activation. We investigated the effects of soluble complement receptor 1 (sCR1),
      a potent complement inhibitor, on both complement and granulocyte activation in
      an ex vivo model of dialysis. Measurements were made of complement activation
      (radioimmunoassay for C3a desArg) as well as granulocyte activation (flow
      cytometric measurements of reactive oxygen species production, granulocyte
      CD11b/CD18 (MAC-1) expression and CD62L (L-selectin) expression). sCR1 completely
      abolished the generation of plasma C3a desArg during ex vivo hemodialysis.
      Without sCR1, C3a desArg levels rose from 968 +/- 373 ng/ml to 4961 +/- 40 ng/ml
      by the end of the ex vivo procedure (p < 0.001). sCR1 also completely inhibited
      MAC-1 upregulation and L-selectin shedding from granulocytes during ex vivo
      hemodialysis. With sCR1 there was still a statistically significant increase in
      granulocyte reactive oxygen species production (from 2.42 +/- 0.1 fluorescence
      channels to 6.47 +/- 0.7 fluorescence channels, p < 0.01) but a 50% inhibition
      when compared with experiments without sCR1 (3.15 +/- 0.5 to 11.2 +/- 1.9, p <
      0.01). We conclude that sCR1 completely abolishes complement activation and
      changes in granulocyte cell adhesion molecules during ex vivo hemodialysis with
      cellulosic membranes. sCR1 partially inhibits granulocyte reactive oxygen species
      formation.

PMID- 7561450
TI  - Desmopressin stimulates the expression of P-selectin on human platelets in vitro.
AB  - Desmopressin (1-desamino-8-D-arginine vasopressin (DDAVP)) is a synthetic analog
      of arginine vasopressin (AVP) and is useful in the treatment of some bleeding
      disorders. The mechanism of improved hemostasis in patients with platelet
      dysfunction is uncertain. Platelet-rich plasma samples from 35 normal subjects
      were incubated with serial dilutions of DDAVP, AVP, and adenosine diphosphate.
      The expression of the platelet activation-dependent antigen CD62 (P-selectin) was
      measured by fluorescent-labeled monoclonal antibody and flow cytometry. DDAVP at
      concentrations of 1.0 to 1000 nmol/L stimulated significant expression of CD62 on
      normal platelets in vitro. At a pharmacologic concentration of DDAVP (1 nmol/L),
      14.1% (0.6% to 45.4%) (median and range) of platelets expressed CD62. There was a
      strong correlation between DDAVP-induced and AVP-induced CD62 expression (rs =
      0.62, p = 0.0008) but not between DDAVP-induced and ADP-induced expression,
      suggesting a V1 receptor-mediated mechanism. Preincubation of platelets with a
      vasopressin V1 receptor antagonist completely inhibited CD62 expression in
      response to DDAVP. We conclude that DDAVP directly activates platelets by
      interaction with the platelet V1 receptor in vitro. This finding may partially
      explain in vivo effects of DDAVP on hemostasis.

PMID- 7561452
TI  - Facts. Kentucky physicians, Medicaid, and the provider tax.

PMID- 7561451
TI  - What's a Holy Grail and why haven't we found it?

PMID- 7561453
TI  - The impact of major congenital malformations on mortality in a neonatal intensive
      care unit.
AB  - Neonatal mortality due to congenital malformations or genetic disorders has not
      decreased despite a decrease in overall neonatal deaths with recent advances in
      medical technology. As a consequence, an increasing percentage of neonatal deaths
      is attributable to congenital malformations and genetic disorders. This study
      retrospectively reviewed neonatal deaths associated with congenital malformations
      over an 11-year period in the neonatal intensive care unit (NICU) at Kosair
      Children's Hospital, Louisville, Kentucky. Presently, congenital malformations
      are responsible for approximately 45% (range 32% to 61%) of deaths in the NICU
      with congenital heart disease, lethal genetic disorders, and pulmonary hypoplasia
      being the main contributors. Other major causes of neonatal death included
      extreme prematurity, respiratory disorders, necrotizing enterocolitis, sepsis,
      asphyxia, and primary pulmonary hypertension. It is important that clinicians are
      aware that improved survival is expected for most diseases because of
      technological advances, but that further significant reductions in neonatal
      mortality will depend on genetic counseling and prevention of congenital
      malformations.

PMID- 7561455
TI  - Ethical dilemmas in a changing health care system.

PMID- 7561454
TI  - John James Moren, MD 1871-1948.

PMID- 7561456
TI  - Management of fecal incontinence.

PMID- 7561457
TI  - Women physicians leading change.

PMID- 7561458
TI  - A quiet talk about time and the E&M codes.

PMID- 7561460
TI  - A remembrance of things past.

PMID- 7561459
TI  - Interprofessional code. Kentucky Medical Association and Kentucky Bar
      Association.

PMID- 7561461
TI  - Canal wall down mastoidectomy: causes of failure, pitfalls and their management.
AB  - Managing patients with failed canal wall down mastoidectomy, requires a
      meticulous approach to control the disease and restore hearing. The present
      article reviews the causes of failure of the primary procedure and pitfalls
      encountered in 105 patients referred to our centre for revision canal wall down
      mastoidectomy. At post-revision surgery there were no cases with residual or
      recurrent cholesteatoma. The failures in our revision procedure were due to
      tympanic membrane perforation which occurred in five per cent (n = 4) and
      intermittent otorrhoea in two per cent (n = 2). A dry cavity with adequate middle
      ear space allowed for optimum audiological function even in revision canal wall
      down procedures.

PMID- 7561462
TI  - Factors associated with recurrence of cholesteatoma.
AB  - After a mean follow-up period of 7.3 years, a recurrence was found in 43 (12.3
      per cent) out of 349 consecutive patients undergoing surgical treatment for
      acquired cholesteatoma. The great majority of residual cholesteatomas detected in
      the 'second-look' operations arose from the oval window area. Chronic otorrhoea
      and a reperforation were the most common signs of late recurrences. In eight ears
      a recurrent cholesteatoma developed from a retraction pocket. The recurrence rate
      was higher in children than in adults. The type of surgical technique had no
      significant effect on recurrence rate. Recurrences were more frequent in pre
      operatively discharging ears than in dry ears. Some suggestions have been made to
      improve the results of surgery for cholesteatoma.

PMID- 7561463
TI  - One-stage procedure to establish osseointegration: a zero to five years follow-up
      report.
AB  - A cohort of 214 patients, who were operated on to insert implants in the mastoid
      process for the retention of bone-anchored hearing aids and auricular prostheses,
      was follow-up over a five-year period. About half the group were operated on
      using the conventional two-stage procedure allowing three to four months for
      osseointegration. In the second group (one-stage group) the skin penetrating
      coupling was connected at the time of the implant insertion. The success rate for
      stable implants was found to be the same in both groups. In the one-stage group
      four out of 161 implants inserted were lost and in the two-stage group three out
      of 120. The cumulative success rate was also found to be the same. A 'worst case'
      table where patients lost to follow-up, patients who died during the study
      period, and patients who for some reason left the study is also included. The
      importance of this 'worst case' scenario when follow-up data are presented is
      discussed.

PMID- 7561464
TI  - Hearing loss and motorcyclists.
AB  - Motorcyclists are known to be exposed to excessive wind noise levels when riding.
      The potential adverse effects of this exposure on their hearing was investigated.
      Temporary threshold shift (TTS) was assessed by asking 18 riders to undertake a
      standard test run of one hour at a steady 80 mph, and performing audiometry
      before and immediately afterwards. Permanent threshold shift (PTS) was assessed
      by performing pure-tone audiograms on a highly screened group of 246
      motorcyclists and comparing their hearing thresholds with those of an appropriate
      control group obtained from the MRC National Study of Hearing. Significant TTS
      was found at 0.25, 0.5, 1 and 2 kHz. The greatest TTS occurred at 1 kHz, with a
      mean hearing loss of 10.3 dB. The hearing thresholds of the motorcyclists were
      significantly worse than the controls at 0.25, 0.5, 1 and 2 kHz, and was most
      marked at 0.5 and 1 kHz where their hearing loss (PTS) was, respectively, 3.7 and
      3.6 dB greater than expected. These findings demonstrate evidence of both
      temporary and permanent hearing loss from motorcycling and present a strong
      argument for the need for some form of remedial action.

PMID- 7561465
TI  - Dilemmas in auditory assessment of developmentally retarded children using
      behavioural observation audiometry and brain stem evoked response audiometry.
AB  - The records of 94 consecutive developmentally retarded children with speech
      retardation and suspected hearing loss who underwent auditory assessment by both
      conventional behavioural observation audiometry (BOA) and brain stem evoked
      response audiometry (BERA) were analysed. In 54 children (57.4 per cent) there
      was good agreement between the results of both techniques leading to a clearcut
      diagnosis. In 22 children a diagnosis was possible only by the results of BERA as
      the results of BOA were inconclusive. Of the remaining 18 children, two groups
      could be identified whose results posed a dilemma. Group 1 (n = 7) consisted of
      children whose BOA test results differed considerably from their BERA results.
      Group 2 (n = 11) consisted of children in whom there was no discernible response
      by BERA while the response by BOA was either inconsistent (n = 5) or not
      elicitable (n = 6). The specific strategies to be adopted for hearing assessment
      in these situations are discussed.

PMID- 7561466
TI  - The influence of race on the position of the jugular bulb.
AB  - The position of the jugular bulb (JB) is of great clinical significance to the
      otologist. A high and laterally situated jugular bulb may pose difficulties when
      dealing with the middle ear while a high and medially sited jugular bulb can
      create problems in neuro-otological surgery. This paper aims to study possible
      racial differences in the position of the jugular bulb. Fine-cut computed
      tomogram (CT) scans of temporal bones (in the axial plane) of 34 Caucasians and
      34 Chinese were studied. The position of the jugular bulb was determined with
      reference to the midpoint of the lumen at the inferior limit of the cochlea
      (mpC). Of the 60 Caucasian and 58 Chinese temporal bones with identifiable
      jugular bulbs, 33 jugular bulbs of the Caucasian (55 per cent) and 34 jugular
      bulbs of the Chinese (58.6 per cent) were at the same height or higher than the
      mpC (p = 0.2; chi-squared test). The midpoint of the jugular bulb was 8.67 +/-
      1.73 and 8.61 +/- 2.49 mm posterior to the mpC for the Caucasian and Chinese
      respectively (p = 0.2; t-test). However, the midpoint of the jugular bulb of
      eight Caucasian (24.2 per cent) and 22 Chinese (64.7 per cent) were medial to the
      mpC (p < 0.001; chi-squared test). Race does not influence the height of the
      jugular bulb nor its position in the sagittal plane but can influence whether a
      high jugular bulb is medially or laterally situated.

PMID- 7561467
TI  - Day-case septal surgery under general anaesthesia and local anaesthesia with
      sedation.
AB  - Septal surgery (submucous resection and septoplasty) has been performed as a day
      case procedure routinely under general anaesthesia and local anaesthesia with
      sedation at the Ipswich Hospital since 1992. The outcome of the day-case septal
      surgery over a period of 18 months has been audited. A total of 95 cases were
      operated on of which 48 were under general anaesthesia (GA) and 47 under local
      anaesthesia (LA) with sedation using midazolam intravenously. The bleeding rate
      and overnight admission rate were 10.5 and 11.4 per cent respectively. The
      bleeding rate was the same in both GA and LA groups. The combination of local
      anaesthesia and sedation has been found to be safe, effective and acceptable to
      patients. It is concluded that septal surgery is suitable as a day procedure and
      that local anaesthesia combined with sedation has a definite place if carried out
      properly.

PMID- 7561468
TI  - A prospective randomized study to assess the efficacy of post-operative nasal
      medication after endonasal surgery.
AB  - Post-operative nasal medications are commonly used following routine septal or
      turbinate surgery but their efficacy in removing blood clots, improving the
      sensation of a patent airway and promoting healing are unknown. This prospective
      randomized trial of patients undergoing septal and/or turbinate surgery assessed
      the efficacy of three commonly used nasal medicines, 0.5 per cent ephedrine
      hydrochloride nasal drops, betamethasone sodium phosphate (Betnosol) nose drops
      and alkaline nasal douches, in producing the sensation of a patent airway in the
      14 days following surgery. Ninety-seven patients were randomized into the three
      treatment groups and a control group who received no nasal medication. Patients
      assessed their nasal patency by means of a visual analogue scale (VAS) and any
      complications of treatment were recorded. Statistical analysis of the 76 complete
      sets of results using the Mann-Whitney U-test showed that there was a significant
      difference in the distribution of all of the treatments for each of the time
      intervals (p < 0.05). Glass rank biserial correlation coefficients were all small
      (rg < 0.085) but the most significant differences were between ephedrine and the
      control group at two hours, two, seven and 10 days (0.02, 0.054, 0.057, 0.085
      respectively), alkaline nasal douches being most significant at four and 14 days
      (0.06 and 0.0722 respectively).

PMID- 7561469
TI  - Arrangement and number of intralaryngeal ganglia and ganglionic neurons:
      comparative study of five species of mammals.
AB  - The arrangement and number of intralaryngeal ganglia and their neurons in five
      mammals (dog, rat, guinea pig, rabbit and cat) were examined morphologically.
      Intralaryngeal ganglions were situated mainly in branches of the internal branch
      of superior laryngeal nerve (Int-SLN), dorsal and/or dorsolateral to the
      posterior cricoarytenoid muscle, and around the inferior laryngeal nerve in dogs,
      rats, guinea pigs and cats, but they were identified at the branching out point
      of the Int-SLN exclusively in rabbits. The ganglion of each animal was spindle
      shaped, with a surrounding fibrous capsule, and it contained many ganglionic
      neurons, vessels and connective tissue cells. The ganglionic neuron was oval
      shaped and had a round nucleus: the diameter was smaller (20-25 microns) in the
      rat than in the other mammals (25-30 microns). More than 80 per cent of
      ganglionic neurons occurred in the supraglottis of all the animals except the
      rat. In the rat, this value was approximately 40 per cent.

PMID- 7561470
TI  - Expression of EGF, EGFR and PCNA in laryngeal lesions.
AB  - The expression of EGF/EGFR in 47 laryngeal surgical specimens from 44 patients
      was examined. PCNA analysis as an index of proliferating cells was also performed
      in 32 cases of laryngeal cancer, six cases of pre-cancerous lesions and nine
      cases of normal laryngeal mucosa. EGFR failed to show a significant correlation
      with tumour behaviour, but EGF expression was statistically significantly higher
      in malignant (SCC) than in non-malignant tissues (pre-cancerous and normal
      tissues) (p < 0.006), and PCNA also showed a statistically significant difference
      (p < 0.016) between the two. In malignant tissues when EGF/EGFR in 'double
      positive' and 'double-negative' cases was compared, a statistically significant
      difference in PCNA was found (p < 0.029); but this was not seen in non-malignant
      tissues. Our results support the hypothesis that an autocrime mechanism exists in
      laryngeal cancer and in this mechanism EGF may play an important role in tumour
      progression, especially when EGFR is overexpressed.

PMID- 7561471
TI  - Amylase activity in tracheobronchial secretions of laryngectomized patients.
AB  - The alpha-amylase activity in tracheobronchial secretions of 16 consecutive
      patients with a total laryngectomy was studied. None of these patients had a
      tracheopharyngeal fistula or pulmonary disorder which might affect the amylase
      activity. This study proves the presence of amylase in tracheobronchial
      secretions of laryngectomized patients with a normal lung at a level between x
      and y and the quantitative analysis of the amylase activity is discussed. The
      relevance of investigating laryngectomy patients is because of the nature of the
      surgery the lower respiratory tract is permanently and physically isolated from
      any other source of salivary amylase. No similar study of the analysis of amylase
      in normal lung tissue had been reported before. This information may be of value
      in order to detect salivary aspiration in patients with a tracheostomy or
      endotracheal intubation if the level in the aspirate is in the order of a-b times
      greater than that found in normal tracheobronchial secretions. (x = 35 and y =
      1125 i.u./l; a = 31.8 and b = 628.6 i.u./l).

PMID- 7561472
TI  - A study of alpha-amylase activity in tracheobronchial secretions of seriously ill
      patients with tracheostomies.
AB  - This study was undertaken to assess any salivary aspiration in seriously ill
      patients with tracheostomies in an Intensive Care Unit setting. The alpha-amylase
      activity in the tracheostomies in an Intensive Care Unit setting. The alpha
      amylase activity in the tracheobronchial secretions of 15 such patients were
      analysed to evaluate the incidence of salivary aspiration. None of the patients
      had clinical or radiological evidence of lung disorder at the time of the
      commencement of the study. Six out of 15 patients showed very high levels of
      alpha-amylase activity in their tracheobronchial secretions on Day 3 and all six
      subsequently developed severe chest infections. The other nine patients showed a
      low level of amylase activity in their secretions. Two patients in the latter
      group developed severe pulmonary disease. This study demonstrates that a high
      level of alpha-amylase activity in the tracheobronchial secretions of
      tracheotomized, ventilated patients indicates that salivary aspiration may be
      taking place, and further suggests that progressively increasing levels may
      indicate the likelihood of a major pulmonary complication developing.

PMID- 7561473
TI  - How I do it: an improved temporal bone holder.
AB  - Although some form of temporal bone holder is in use in virtually all ENT
      postgraduate teaching departments, a paucity of information in the literature may
      cause problems in selecting the most appropriate model to those responsible for
      equipping temporal bone laboratories. The bone holder which we describe is based
      on existing designs but incorporates a built-in irrigation system which offers
      considerable advantages to the unassisted operator.

PMID- 7561475
TI  - Recurrent massive epistaxis due to traumatic intracavernous internal carotid
      artery aneurysm.
AB  - Traumatic internal carotid artery aneurysm presenting with epistaxis is rare.
      Epistaxis often occurs after a delay of weeks to months following head injury.
      The present case had bouts of recurrent massive epistaxis nearly four months
      after head injury. Diagnosis was made after carotid angiography. Epistaxis ceased
      after ipsilateral carotid ligation.

PMID- 7561476
TI  - Huge saccular cyst of the larynx: a case report.
AB  - Lateral laryngeal saccular cysts of the larynx that herniate through the
      thyrohyoid membrane are quite rare. We present a case of a huge midcervical cyst
      which occurred as a result of extreme neglect of a lateral saccular cyst. This
      case provided us with a unique opportunity to characterize the late stages of
      this pathology. The differential diagnosis of cervical cysts and treatment
      approaches are discussed.

PMID- 7561477
TI  - Lemierre syndrome--a forgotten complication of acute tonsillitis.
AB  - Lemierre syndrome, also known as postanginal sepsis, is an illness characterized
      by the development of a fusobacterial septicaemia with multiple metastatic foci
      following an attack of acute tonsillitis. It typically affects previously healthy
      adolescents and young adults who, following an attack of sore throat, become
      acutely ill with hyperpyrexia, rigors and multiple metastatic abscesses. The
      clinical picture tends to vary widely because of the possible involvement of a
      number of body systems and organs in the disease process. This serious
      complication of oropharyngeal sepsis had a mortality rate in excess of 90 per
      cent in the pre-antibiotic era. Although now rarely seen and often forgotten, it
      remains a potentially life-threatening condition. We present four cases of post
      tonsillitis fusobacterial septicaemia to illustrate the variability of the
      clinical presentation and stormy clinical course frequently associated with this
      rare syndrome.

PMID- 7561478
TI  - Tonsillar lipoma: a case report.
AB  - Benign tumours of the tonsils are rare. Only a few cases of tonsillar lipoma have
      been previously reported. The case of a pedunculated polypoid lipoma of the
      palatine tonsil in a 44-year-old Japanese woman is presented. The 'polyp' was
      excised and an histopathological examination was carried out. The 'polyp'
      contained dilated lymphatics in the dense fibrous connective tissue beneath the
      overlying mucosal epithelium and below the mature fat tissue with intervening
      strands of fibrous tissue.

PMID- 7561479
TI  - Angiomatous malformation of the floor of the mouth associated with fluctuating
      macroglossia in an adult: an unusual case report.
AB  - We report an unusual case of a large vascular lesion of the floor of the mouth of
      rapid onset in a 50-year-old man who presented with an external swelling in the
      submental region and a history of fluctuating swelling of the tongue. The
      clinical features, investigations, treatment and course of this rare condition
      are discussed.

PMID- 7561480
TI  - Ectopic salivary gland in the posterior triangle of the neck.
AB  - Ectopic cervical salivary tissue may present as a discharging sinus if a duct
      system and cutaneous orifice are present. Where described in previous reports
      these openings have been located along the anterior border of sternomastoid or in
      the anterior triangle, making this a differential diagnosis of a branchial sinus.
      We report on a patient who presented with an ectopic salivary gland in the
      posterior triangle of the neck.

PMID- 7561474
TI  - Neuralgia-like symptoms in a patient with an airgun pellet in the ethmoid sinus:
      a case report.
AB  - An unusual case of a retained airgun pellet in the ethmoid sinus is presented.
      The patient's only complaint was a severe neuralgic headache. Anatomical basis
      for this symptom, imaging and successful endoscopic removal of the foreign body
      are discussed. The philosophy for removal of innocuous foreign bodies, potential
      pitfalls in surgical management, and a review of the literature are included in
      the discussion.

PMID- 7561481
TI  - Seeding of a parotid pleomorphic adenoma.
AB  - Recurrent pleomorphic adenoma of the parotid usually occurs in the distribution
      of the primary procedure. There are numerous reports of widespread local
      recurrence and a few reported cases of distant metastases. Extensive seeding
      throughout the entire ipsilateral neck is rare. Treatment involves a combination
      of radical surgery and radiotherapy. The potential for malignant transformation
      demands close follow-up of younger patients particularly.

PMID- 7561483
TI  - Carcinoma ex-pleomorphic adenoma of the nasal cavity: a report of two cases.
AB  - Carcinoma ex-pleomorphic adenoma is exceedingly rare in sites other than the
      major salivary glands and the oral cavity. We present the first two
      histopathologically documented examples to occur in the nasal cavity.

PMID- 7561482
TI  - The importance of thyroid scanning in neck lumps--a case report of ectopic tissue
      in the right submandibular region.
AB  - We describe the case of a 50-year-old previously well female, who presented with
      a slowly growing mass in the right submandibular region. Imaging confirmed the
      absence of a normally placed thyroid and the presence of a lingual thyroid. The
      submandibular mass was excised and histological examination confirmed ectopic
      thyroid tissue. The embryological descent of the thyroid and the Sistrunk
      procedure are discussed as well as the importance of thyroid scanning in neck
      lumps.

PMID- 7561484
TI  - Malignant fibrous histiocytoma of the floor of the mouth: case report.
AB  - Malignant fibrous histiocytoma (MFH) is a common neoplasm of soft tissue. The
      floor of the mouth is an unusual site of origin and has not been described in the
      literature previously. Its rarity, aspecific clinical symptoms and complex
      histopathology combine to make the diagnosis difficult. The treatment of choice
      is wide surgical excision with adjunctive irradiation.

PMID- 7561485
TI  - Spindle cell carcinoma of the parotid gland.
AB  - Spindle cell carcinomas of the salivary gland are extremely rare, with only a few
      cases having been previously reported. We present a 55-year-old man with a
      rapidly enlarging mass in the left parotid gland. Despite radical surgery, the
      tumour recurred, and led to death 11 months later. Histopathologically, the
      tumour was composed of two components, a squamous cell carcinoma component and a
      spindle cell sarcomatoid component. A diagnosis of primary spindle cell carcinoma
      of the parotid gland was made. Immunohistochemical studies revealed keratin
      positivity and vimentin negativity in the squamous cell carcinoma component: the
      spindle cell sarcomatoid component was positive for vimentin and negative for
      keratin, but showed focal positivity for epithelial membrane antigen. The origin
      of the sarcomatoid component and the differential diagnosis from malignant mixed
      tumours are discussed.

PMID- 7561486
TI  - Endoscopic sinus surgery.

PMID- 7561487
TI  - Perilymphatic fistula--the challenging enigma. Methods of intraoperative
      diagnosis.

PMID- 7561488
TI  - Osteoplastic changes in attic cholesteatoma.
AB  - Eighty-nine cases of attic type cholesteatoma were operated on during a three and
      a half-year period. Of these, eight cases were characterized by bony tissue
      proliferation at the aditus ad antrum or mastoid antrum. Sex, age, and hearing
      levels were not significant in these cases. Bony fixation of the incus and the
      malleus was seen in six cases. Bony tissue blocked further expansion of attic
      cholesteatoma at the aditus in four cases, narrowed the epithelial tract to the
      antrum in two cases, and completely separated the cholesteatoma into two
      cholesteatomas in two cases. Infectious stimuli, at an early stage of the
      disease, might stimulate such osteoplastic activity at the aditus. Axial CT scans
      give useful information regarding structure before surgery.

PMID- 7561489
TI  - Eye protection during mastoid surgery.
AB  - A questionnaire was sent to all Full Members of the British Association of
      Otolaryngologists to ascertain whether and what type of eye protection surgeons
      and theatre nurses wear during mastoid surgery. Despite Department of Health
      recommendations only 58 per cent of surgeons and 19 per cent of theatre nurses
      routinely wear any form of eye protection.

PMID- 7561490
TI  - Causes of failure of combined approach tympanoplasty in the treatment of acquired
      cholesteatomas of the middle ear and the mastoid.
AB  - Forty cases of failed combined approach tympanoplasty were analysed. The
      commonest cause of failure was adhesions between the facial ridge and the
      tympanic membrane, causing segmental attico-mastoid malaeration in 51.3 per cent
      of cases followed-up continually. Other causes were, large dermoids, incomplete
      removal of squamous epithelium, and eustachian tube obstruction. Eustachian tube
      dysfunction did not appear to be a major cause of failure.

PMID- 7561491
TI  - Inner ear involvement in rheumatoid arthritis: a prospective clinical study.
AB  - Sensorineural hearing loss in rheumatoid arthritis (RA) has been reported to be
      the result of the extra-articular manifestation of the disease (rheumatoid
      nodular vasculitis) or due to drug ototoxicity. In an attempt to investigate the
      presence of sensorineural hearing loss and the possible causes for it we
      investigated prospectively 45 RA patients (42 female; three male) with a mean age
      of 52.5 +/- 10.7 years and a mean disease duration of 8.5 +/- 7.3 years. All
      patients underwent a complete physical examination and audiological evaluation
      which included pure tone audiometry and impedance audiometry (tympanogram, static
      compliance, acoustic reflex, reflex decay, acoustic reflex latency test. We found
      a sensorineural hearing loss > 20 dB HL in 44.4 per cent (40/90) ears. In all
      cases the site of hearing loss was the cochlea and in most of them it was
      bilateral and symmetric (16 patients out of 45 had bilateral sensorineural
      hearing loss i.e. 35.5 per cent. There was no correlation between sensorineural
      hearing loss and age, sex, disease duration, articular and extra-articular
      manifestations and the presence of autoantibodies in our patients. In addition,
      no correlation was found between sensorineural hearing loss and drug therapy for
      one at least of the following drugs: NSAIDs, D-penicillamine, plaquenil and
      methotrexate. We noticed a prologation of acoustic reflex latency in five
      patients (10 per cent) which was found to be correlated with the
      temporomandibular joint involvement and the presence of rheumatoid factor (RF).
      We conclude that inner ear involvement in RA is expressed by: (1) mild symmetric,
      bilateral sensorineural hearing loss of cochlear type in 35.5 per cent of
      patients; (2) normal acoustic reflex thresholds; (3) nondecay; and (4)
      prologation of acoustic reflex latency which appeared in a small number of
      patients (10 per cent).

PMID- 7561492
TI  - Syphilitic labyrinthitis--an update.
AB  - Forty-eight patients with syphilitic labyrinthitis have been treated and followed
      up for periods of six months to 25 years; interpretation of the hearing results
      must be in the light of the natural history of this condition which is perceived
      to be progression of hearing loss to profound deafness. At the beginning of the
      series treatment was with ampicillin alone and on this treatment 11 ears with
      useful hearing were maintained at this level. The group with combined ampicillin
      and prednisone treatment, which included some failures from ampicillin alone,
      maintained useful hearing in 28 out of 29 ears. Those treated initially with
      ampicillin and prednisone and later also given regular injections of ACTH,
      maintained hearing in 16 out of 17 ears. At the outset, there were 29 profoundly
      deaf ears. One of these recovered some useful hearing but two ears with useful
      hearing at the outset became profoundly deaf so that at the end there were 30
      profoundly deaf ears. However, all patients as opposed to ears, with useful
      hearing at the outset were left with some hearing; no patient became profoundly
      deaf.

PMID- 7561493
TI  - Raised ABR threshold after suction aspiration of glue from the middle ear: three
      case studies.
AB  - Between 1991 and 1993, 13 children (25 hearing ears) underwent recordings of the
      auditory brain stem response (ABR) under a general anaesthetic. The anaesthetic
      technique was similar for each child. Fourteen of these ears had fluid aspirated
      after myringotomy with insertion of grommets prior to the auditory brain stem
      response investigation. On subsequent hearing assessment six of these 14 ears (43
      per cent) showed clear evidence of a threshold shift of 15 dB or greater. Eleven
      ears had either dry myringotomies or did not have a myringotomy prior to ABR and
      none of these showed evidence of a temporary threshold shift. Using Fisher's
      Exact probability test this difference is significant (p = 0.034). We feel it is
      important to report these observations so that unexpected high ABR thresholds
      following aspiration of glue are interpreted with caution.

PMID- 7561494
TI  - Cryotherapy in the treatment of nasal obstruction: indications in adults.
AB  - Cryotherapy is an established method of treating hypertrophic obstructive
      inferior turbinates. The long-term effectiveness of the technique is assessed in
      this study, using the need for alternative nasal surgery as an objective way of
      distinguishing success from failure. Over 50 per cent of patients with
      obstructive symptoms, including those with minor septal deviation or allergy
      derived lasting benefit from the technique. Cryotherapy is an effective means of
      treating nasal obstruction due to mucosal hypertrophy of the turbinates and may
      replace the need for more radical surgery.

PMID- 7561495
TI  - Paediatric tonsillectomy: bipolar electrodissection and dissection/snare
      compared.
AB  - Tonsillectomy is a common operation in children performed by a variety of
      techniques. Recently we have introduced a modified form of electrodissection
      tonsillectomy using bipolar diathermy. A prospective study was designed to
      evaluate this technique against the conventional dissection/snare technique.
      Sixty children were entered into each section of the study (total 120 children).
      There is a statistically significant shorter operating time (mean 11.2 minutes)
      and lower intraoperative blood loss (mean 5 ml) using the bipolar diathermy
      technique. Post-operatively, the children who had bipolar diathermy tonsillectomy
      were found to be able to drink and eat significantly earlier than the cold
      dissection group. There was no measurable difference in analgesia requirements
      before discharge and the time of discharge between the two methods. Post
      operative haemorrhage occurred in two out of 60 (3.4 per cent) and one out of 60
      (1.7 per cent children) in the conventional and bipolar diathermy dissection,
      respectively, but this was not statistically significant.

PMID- 7561496
TI  - Age and sex incidence of hypopharyngeal tumours in upper Egypt: Assuit University
      experience.
AB  - Three hundred and seventeen patients with hypopharyngeal tumours presented at
      Assuit University Hospital and were studied retrospectively with regard to sex
      and age incidence. Postcricoid tumours form the majority (50.1 per cent) followed
      by pyriform fossa tumours (26.5 per cent) and finally posterior pharyngeal wall
      tumours (23.4 per cent). Men form the majority (211 out of 317, i.e. 69.7 per
      cent). The age incidence shows two peaks at 31-35 years and 56-60 years. The
      first peak is formed mainly of women while the second peak is formed mainly of
      men.

PMID- 7561497
TI  - Clinical photographs as teaching aids: how reliable are they?
AB  - A study to investigate the value and reliability of clinical photographs as
      teaching aids was undertaken. Twenty colour photographs were taken using the
      StarMed video-otoscopic system. The pictures, which were a mixture of normal and
      abnormal ears, were shown to 21 experienced otolaryngologists from the UK and
      Canada. These clinicians were asked to identify the abnormality if any. The
      median score for correctly identified pictures was 15 (range 12-18). This score
      was identical for both the UK and Canadian subgroups. Although the abnormalities
      were consistently well recognized with an average correct identification rate of
      90 per cent (range 67-100 per cent), the 'normals' were recognized significantly
      less well at only 41 per cent (range 5-71 per cent) (chi-squared = 110.6; 1 df; p
      < 0.001). This result is probably due to failure of the camera to capture the
      huge variation and subtleties in the range of normal, and the clinicians' natural
      inclination to identify pathology, when in doubt. We would conclude that as long
      as this failing is recognized, clinical photographs, and specifically those from
      the video-otoscope, represent a useful and reliable teaching tool.

PMID- 7561498
TI  - Audiological findings in a Phase I protocol investigating the effect of WR 2721,
      high-dose cisplatin and radiation therapy in patients with locally advanced
      cervical carcinoma.
AB  - WR 2721 (ethiofos) protects against the toxic effects of the heavy metal compound
      cisplatin, which is used in the treatment of solid tumours. In a Phase I protocol
      designed to determine the maximum dose of WR 2721 which could be tolerated when
      administered in combination with cisplatin and radiation therapy to patients with
      cervical carcinoma, 11 patients were evaluated by audiologic testing before and
      after cisplatin WR 2721 administration in an attempt to identify the degree of
      ototoxicity. Forty-five per cent were noted to have significant hearing threshold
      changes, predominantly in the high frequencies. There were no significant changes
      in the speech frequencies in this series. This contrasts with the greater degrees
      of ototoxicity observed in controls treated in the same way who received
      cisplatin without WR 2721 protection.

PMID- 7561499
TI  - Life-size photograph transparencies: a method for the photographic detection and
      documentation of recovery from facial paralysis.
AB  - We describe a simple and objective practical method for the detection of recovery
      from facial paralysis by multiple photographic assessments. The photographs are
      printed as life-size transparencies representing maximal effort. Each time the
      patient attends for review the new transparency is overlapped on the previous one
      and the difference can be detected easily. The prints are filed with the
      patient's notes for future reference. To achieve this system a specific
      photographic protocol is mandatory in order to avoid technical artefacts. We
      believe that this system avoids many of the complexities of other grading systems
      and is very suitable for use at outpatient follow-up.

PMID- 7561500
TI  - Non-Hodgkin's lymphoma of the external auditory canal in an HIV-positive patient.
AB  - This is a case report of non-Hodgkin's lymphoma of the external auditory canal,
      and infratemporal fossa, which presented with multiple cranial nerve palsies. The
      diagnosis was achieved via biopsy of tissue from the external auditory canal, and
      treatment with radiation therapy led to improvement of the symptoms. The
      management of AIDS-related lymphoma of the skull base with cranial neuropathies
      is reviewed.

PMID- 7561501
TI  - Non-cholesteatomatous suppurative otitis media: facial nerve palsy in an
      immunocompromised patient.
AB  - A 47-year-old man developed a complete facial nerve palsy secondary to non
      cholesteatomatous suppurative otitis media. At operation, this was seen to be due
      to destruction of the nerve from halfway along the horizontal segment to a point
      just distal to the second genu. The history of recent renal transplantation and
      subsequent immunosuppression was judged to be significant in the pathogenesis of
      the palsy.

PMID- 7561502
TI  - Metastatic adenocarcinoma of the ethmoids in a patient with previous gastric
      adenocarcinoma: a case report.
AB  - Metastatic carcinoma of the ethmoids is very rare. Of the few cases reported in
      the literature, the majority are renal in origin. Although metastases from the
      gastrointestinal tract have been reported, there are no known cases of metastases
      from the stomach. We present a rare case of metastatic adenocarcinoma of the
      ethmoids in a patient previously treated for adenocarcinoma of the stomach and
      describe the possible mechanisms of spread. The patient had a craniofacial
      resection of the tumour but unfortunately died four weeks post-operatively from
      acute liver failure probably caused by a liver metastasis.

PMID- 7561503
TI  - Laryngeal carcinoma ex-papilloma in a non-irradiated, non-smoking patient: a
      clinical record and review of the literature.
AB  - Malignant transformation of respiratory papillomata is not uncommon in the
      presence of precipitating factors such as tobacco smoking and therapeutic
      irradiation. Respiratory papilloma changing to carcinoma in the absence of
      smoking and irradiation is seldom seen, with only about 20 documented cases
      presented in the literature. Here we report one such case in a 30-year-old male
      patient.

PMID- 7561506
TI  - Deep lobe parotid lipoma: a case report.
AB  - We present a patient with a lipoma of the deep lobe of the parotid gland. Despite
      the common occurrence of this tumour in other regions of the body, we believe
      that this is only the second report in the literature of a lipoma in this
      location. We believe that these tumours are easily dealt with by simple
      enucleation, and that superficial parotidectomy should be reserved for tumours
      deep to the facial nerve.

PMID- 7561504
TI  - Salivary megalith with a sialo-cutaneous and a sialo-oral fistula: a case report.
AB  - A rare case of a salivary megalith with a sialo-cutaneous and a sialo-oral
      fistula in an elderly man is presented. A brief review of the literature is made.

PMID- 7561505
TI  - Tongue paralysis following head trauma.
AB  - Paralysis of the tongue due to isolated bilateral hypoglossal nerve palsy is a
      rare occurrence. Due to a trauma the cause in our case may have been a traction
      injury to both hypoglossal nerves at the base of skull. In some cases a
      contributing factor may be malformation of the skull base. Most cases have a good
      prognosis for recovery.

PMID- 7561507
TI  - Excision of adenoid cystic carcinoma of the cervical trachea via an anterior
      castellated approach.
AB  - Adenoid cystic carcinoma of the cervical trachea is rare and its diagnosis and
      surgical management challenging. We report a case with an unusual presentation
      and discuss the diagnosis and management. The preferred surgical management is
      tracheal resection, however this is often not feasible and many alternative
      techniques have been used. Here an anterior castellated approach is described, a
      modification of that more commonly used for benign tracheal strictures. We found
      it gave excellent access to the posterior tracheal wall which we feel is superior
      to a straight vertical tracheal incision. It also facilitates a tracheal widening
      procedure if indicated, and safeguards the recurrent laryngeal nerves which are
      particularly vulnerable in the cervical part of the trachea.

PMID- 7561509
TI  - Lymphoma and Hashimoto's thyroiditis.
AB  - Development of malignant lymphoma in Hashimoto's thyroiditis is well documented.
      A case of tracheal invasion by a lymphoma which accompanied Hashimoto's disease
      is described. The clinical and diagnostic difficulties which were encountered are
      presented. The magnetic resonance imaging (MRI) findings which have not been
      reported previously are outlined.

PMID- 7561510
TI  - Laryngeal squamous cell carcinoma with sebaceous differentiation.
AB  - A case of supraglottic laryngeal squamous cell carcinoma with sebaceous
      differentiation in a 68-year-old Caucasian male is described. A right cervical
      lymph node metastasis, excised during the laryngectomy operation, consisted
      exclusively of squamous cells. Despite intensive post-operative chemotherapy, the
      patient developed metastatic foci in the left cervical area and left pulmonary
      hilus and died seven months later. This is the second case report of a laryngeal
      squamous cell carcinoma with sebaceous differentiation in the literature.

PMID- 7561508
TI  - Early diagnosis and treatment of Ramsay Hunt syndrome: the role of magnetic
      resonance imaging.
AB  - We present the case of a 47-year-old woman with left otalgia, rotatory vertigo,
      sensorineural hearing loss and acute facial nerve palsy. An enhanced magnetic
      resonance imaging (MRI) scan showed discrete enhancement of the facial and
      vestibulocochlear nerves in the left internal auditory canal as well as of the
      labyrinth. This appearance was compatible with that in Ramsay Hunt syndrome and
      acyclovir was started prior to the appearance of any vesicular eruption. The
      diagnosis was subsequently confirmed serologically. She regained full facial
      function but the sensorineural hearing loss persisted. The literature pertaining
      to the role of the MRI in acute facial palsies is reviewed.

PMID- 7561511
TI  - Recurrent sialadenoma papilliferum of the buccal mucosa.
AB  - Sialadenoma papilliferum is a rare, benign, exophytic tumour of the salivary
      glands. The prognosis is exceptionally good. Since the lesion was first
      described, 30 cases have been reported in the English literature, and only one of
      these is known to have recurred. A case of sialadenoma papilliferum occurring in
      the buccal mucosa with recurrence three years after local excision, is presented.
      The literature is briefly discussed.

PMID- 7561512
TI  - Role of interferon-gamma in immune cell regulation.
AB  - In 1965 Wheelock reported that phytohemagglutinin could induce from human
      leukocytes an interferon-like virus inhibitor [1]. This substance, which turned
      out to be interferon-gamma (IFN-gamma), has been the subject, directly or
      indirectly, of thousands of scientific publications since that initial report.
      Past research has led to the general conclusion that IFN-gamma is much more than
      an interferon in that it has broader effects on the various arms of the immune
      system than most any other lymphokine or cytokine. In this review we discuss the
      effects of IFN-gamma on the various cell lineages of the immune system, focusing
      on the biology of its actions. In addition, we summarize research focused on the
      consequences of introducing IFN-gamma cDNA into tumor cells, aberrant IFN-gamma
      production in transgenic animals, and inhibition of IFN-gamma effects by knocking
      out either the IFN-gamma gene itself or the IFN-gamma receptor gene.

PMID- 7561513
TI  - Natural resistance to infection with intracellular parasites: molecular genetics
      identifies Nramp1 as the Bcg/Ity/Lsh locus.
AB  - Natural resistance to infection with intracellular parasites is controlled in the
      mouse by the expression of a locus or group of loci on chromosome 1 alternatively
      named Bcg, Lsh, and Ity. Bcg affects the capacity of mature tissue macrophages to
      restrict the intracellular proliferation of ingested parasites in the
      reticuloendothelial organs of the host during the early phase of infection. This
      review summarizes our molecular genetic approach to the isolation and
      characterization of the Bcg locus. 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, named Nramp1, which codes for a macrophage-specific
      polytopic protein with 12 predicted transmembrane domains and a consensus
      transport motif. Sequence analysis of Nramp1 cDNA clones from 27 Bcgs and Bcgr
      mouse strains reveals that susceptibility to infection (Bcgs) is associated with
      a single nonconservative Gly to Asp substitution at position 169 within predicted
      transmembrane domain 4 of the Nramp protein. Cloning experiments and homology
      search in available databases demonstrated that the Nramp1 gene belongs to a
      small gene family with several members in vertebrates and in such distantly
      related species as yeast and plants. Nramp proteins share a remarkable degree of
      similarity, with strong amino acid sequence conservation in the transmembrane
      domains, suggesting a common transport function for the Nramp family. Finally, we
      generated Nramp1-/- gene knockout mice, and analysis of their phenotypic
      characteristics established that (1) Nramp1 plays a key role in natural defense
      against infection with intracellular parasites and therefore demonstrated
      allelism between Nramp1 and Bcg/Ity/Lsh, (2) Nramp1 functions by a novel
      cytocidal/cytostatic mechanism distinct from those expressed by the activated
      macrophage, and (3) the Nramp1Asp169 allele of Bcgs inbred strains is a null
      allele, pointing to a critical role of this residue in Nramp1 function.

PMID- 7561514
TI  - Involvement of nitric oxide in the regulation of peripheral blood leukocyte
      counts.
AB  - A role for nitric oxide (NO) in the regulation of blood leukocyte numbers was
      examined in BALB/c mice by employing the NO synthase inhibitor NG-nitro L
      arginine methyl ester (L-NAME). Treatment of animals with a single dose of 50
      mg/kg body wt caused a dramatic increase in the number of circulating neutrophils
      and a moderate decrease in the number of circulating lymphocytes. These effects
      were partially reversed by the simultaneous inoculation of L-arginine (250 mg/kg
      body wt.) but not by D-arginine. A second NO synthase inhibitor, NG-nitro L
      arginine, induced changes comparable to those elicited by L-NAME. Because
      catecholamines and glucocorticoids are well-known modulators of blood leukocyte
      counts, experiments were carried out in adrenalectomized mice. It was found that
      adrenalectomy did not modify the increase in the number of circulating
      neutrophils induced by L-NAME but completely prevented the decrease of
      circulating lymphocytes. Taken together, these findings support the hypothesis
      that NO plays an important role in the regulation of the peripheral blood number
      of neutrophils and lymphocytes, and that this function involves, in each case,
      the participation of different mechanisms.

PMID- 7561515
TI  - Pleural fluid eosinophils suppress local IgE-mediated protein exudation in rats.
AB  - Eosinophils are supposed to play a critical role in the pathology of several
      allergic diseases because after activation they can release toxic and
      proinflammatory agents. In this study we have investigated whether IgE-mediated
      rat pleurisy could be affected by an ongoing pleural eosinophilic inflammatory
      response. IgE-passively sensitized rats were challenged with an intrapleural
      (i.pl.) injection of allergen (dinitrophenylated bovine serum albumin, 1
      microgram/cavity) and exudation assessed by measuring the amount of protein
      extravasated into the pleural cavity within 4 h. We have confirmed that
      lipopolysaccharide (LPS) stimulation (250 ng/cavity i.pl.) was followed by a
      marked pleural neutrophilia, apparent at 3 h, which was followed by an eosinophil
      accumulation noted within 48-72 h postchallenge. We have also confirmed that a
      boiled sample of LPS pleural washing (LPS-PW, 200 microliters i.pl.) caused
      selective eosinophilia in recipient rats. Pleural exudation remained unaltered
      when the allergenic challenge was performed 3 h after LPS in a condition of
      intense pleural fluid neutrophilia. In contrast, this was significantly reduced
      (P < .001) when the challenge occurred 72 h after LPS or 24 h after LPS-PW in
      selective pleural fluid eosinophilia. In another series of experiments repeated
      daily i.pl. injections of platelet-activating factor (PAF; 1 microgram/cavity)
      resulted in a progressive increase in eosinophil number recovered from the
      pleural cavity. The values were 1.2 +/- 0.2, 3.0 +/- 0.2, and 5.8 +/- 0.5 x 10(6)
      eosinophils/cavity (mean +/- SEM) after 0, 1, and 4 injections, respectively.
      Allergen challenge performed after 0, 1, or 4 PAF stimulations led to pleural
      protein levels of 88.6 +/- 5.7, 33.7 +/- 0.7, and 19.4 +/- 2.3 mg/cavity,
      respectively, indicating that the allergic pleurisy is inhibited in a manner
      dependent on the magnitude of eosinophil accumulation. Furthermore, the
      impairment of PAF-induced eosinophil accumulation by cetirizine (30 mg/kg i.p.)
      restored the exudatory response. Exudation triggered by compound 48/80 (25
      micrograms/cavity), histamine (200 micrograms/cavity), or 5-hydroxytryptamine
      (100 micrograms/cavity) was not affected by four previous PAF daily injections.
      The findings indicate that allergen-induced exudation is selectively down
      regulated in the eosinophil-enriched pleural space of rats, a suppression that
      increased with increasing eosinophil number and disappeared after chemical
      impairment of the eosinophilia.

PMID- 7561516
TI  - Neutrophil functional responses depend on immune complex valency.
AB  - Ligand-induced cross-linking of Fc gamma receptors (Fc gamma R) on neutrophils
      plays a significant role in their stimulation, shown here by contrasting the
      responses induced by low valency immune complexes (LICs) and high valency immune
      complexes (HICs) and by cross-linking LICs in situ (L/Ab) after their addition to
      the cells. Multiparameter flow cytometry was used to measure immune complex (IC)
      elicited changes in cytoplasmic Ca2+ concentration and initiation of the
      oxidative burst simultaneously in the same cell and to correlate these with Fc
      gamma R occupancy. We have previously shown that subpopulations of neutrophils
      respond maximally to subsaturating concentrations of HIC; saturating dosages
      stimulate the entire population. This discrepancy was not due to differences in
      receptor occupancy. The magnitude of the transient Ca2+ increase was independent
      of the dose of HIC but depended on the dose when an LIC was used. As shown here,
      L/Ab cross-linking elicited Ca2+ responses similar to those observed in HIC
      stimulated cells. In contrast, LIC elicited only minimal intracellular delta pH
      and no oxidative burst or membrane potential changes at all unless Fc gamma R was
      cross-linked, accomplished by HIC or by L/Ab. However, azurophilic degranulation,
      as determined by elastase release, was not observed in cells stimulated by the in
      situ cross-linking method, whereas the HIC preparation triggered azurophilic
      degranulation. Thus, some Fc gamma R-mediated neutrophil effector functions such
      as azurophilic degranulation and oxidative burst initiation have an absolute
      requirement for Fc gamma R cross-linking, whereas signaling functions such as
      changes in membrane potential, intracellular pH, and intracellular Ca2+
      concentration can occur, albeit more slowly and to a lesser extent, if single Fc
      gamma R are occupied.

PMID- 7561517
TI  - Role of the Fc gamma R subclasses Fc gamma RII and Fc gamma RIII in the
      activation of human neutrophils by low and high valency immune complexes.
AB  - Two Fc gamma receptor (Fc gamma R) subclasses on human neutrophils, Fc gamma RII
      and Fc gamma RIII, activate different cellular functions. To examine the
      involvement of each receptor subtype in polymorphonuclear leukocyte activation,
      Fab and F(ab')2 fragments of subclass-specific monoclonal antibodies ([mAbs] mAb
      IV.3 against Fc gamma RII and mAb 3G8 against Fc gamma RIII, respectively) were
      used to block the binding of low valency immune complexes (LICs) and high valency
      immune complexes (HICs). Flow cytometry then permitted the simultaneous
      quantitation of antibody and ligand binding, the elicited intracellular Ca2+
      concentration (delta[Ca2+]int), initiation of the oxidative burst, and/or the
      phospholipase A activation in the same cell. We have previously demonstrated that
      subsaturating dosages of HIC bind uniformly to all the cells but elicit an "all
      or-none" (i.e., dose independent) maximal delta[Ca2+]int in a dose-dependent
      subpopulation of the cells. In contrast, both the proportion of cells responding
      and the magnitude of the delta[Ca2+]int transient depend on the subsaturating
      dose of LIC, even though it too binds uniformly to all the cells, nonresponding
      as well as responding. These earlier findings have here been extended by single
      cell flow cytometric analysis to demonstrate that F(ab')2 Fc gamma RIII is the
      major Fc gamma R involved in HIC binding (and [Ca2+]int mobilization), as well as
      in oxidative burst and phospholipase A activation. In contrast, both receptor
      subclasses must be available for LIC-elicited delta[Ca2+]int, as blockage by
      either of the mAb Fab or F(ab')2 fragments abrogates this response, even though
      LIC binding to the receptors is not decreased. Furthermore, LIC elicited little
      oxidative burst activity and failed to activate phospholipase A but cross-linking
      to achieve multivalency, previously shown to induce [Ca2+]int and oxidative burst
      responses, elicited phospholipase A activity via Fc gamma RIII. Fc gamma RII's
      role appears to be modulation of the small, late Ca2+ influx observed at > 1 min,
      whereas Fc gamma RIII modulates all the earlier larger events. Thus, simultaneous
      observation of receptor identity, receptor occupancy, and consequent activation
      parameters in the same cell by flow cytometry permits use to demonstrate that Fc
      gamma RII is necessary for the small signal transduction elicited by LIC; it
      plays a relatively small role in polymorphonuclear leukocyte stimulation by HIC.
      Fc gamma RIII is the main receptor responsible for immune complex-elicited
      polymorphonuclear leukocyte responses; its efficacy is greatly enhanced when the
      receptors are cross-linked, either by preequilibrated multivalent complexes or by
      in situ cross-linking of bound LIC with excess antibody.

PMID- 7561519
TI  - Colony-stimulating factor-1 expression in the human fetus and newborn.
AB  - Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that
      regulates the survival, proliferation, and differentiation of mononuclear
      phagocytes. Because this cellular compartment undergoes major changes during
      fetal and neonatal life, we examined concurrent CSF-1 expression during human
      development. While levels increased dramatically after full-term birth, CSF-1
      concentrations steadily declined in the preterm circulation from 2.7 to 1.9 times
      adult values as gestational age increased. CSF-1 was already detectable at 10
      weeks gestation in spleen, intestine, lung, kidney, heart, and liver in order of
      decreasing concentration, but a positive correlation with gestational age was
      seen only in lung and intestine. Although a 4.4-kb CSF-1 mRNA was detectable in
      all tissues at all gestational ages, increased expression with advancing
      gestational age was observed in lung and kidney, whereas a rise and fall was
      observed in spleen. We conclude that CSF-1 concentration in the human circulation
      is developmentally regulated and that its expression in fetal tissues is
      compatible with its role in regulating the development of tissue mononuclear
      phagocytes.

PMID- 7561518
TI  - Enhanced expression of novel CD57+CD8+ LAK cells from cats infected with feline
      immunodeficiency virus.
AB  - As a model for lymphokine-activated killer (LAK) function in HIV infection, we
      studied LAK cells in cats infected with feline immunodeficiency virus (FIV),
      which causes an acquired immunodeficiency syndrome. Peripheral blood mononuclear
      cells cultured in concanavalin A and interleukin-2 developed LAK cytotoxicity
      against chronically FIV-infected CrFK cells and acutely infected CD4+ lymphocytes
      but not uninfected cells. LAK cells from FIV+ cats were more cytotoxic than LAK
      cells from uninfected cats. Enhanced FIV+ LAK cytotoxicity against feline
      leukemia virus-infected cells (FL74) suggested that the cytotoxicity was not
      antigen specific. Two-color fluorescence-activated cell sorter analysis and
      antibody depletion studies demonstrated that the majority of LAK cells and their
      progenitors were positive for both CD8 and CD57. The in vitro induction of dual
      positive CD8+CD57+ LAK cells was enhanced in FIV+ cats, as reported for HIV+
      patients. These CD8+CD57+ LAK cells may play a role in maintaining the long
      asymptomatic stage of infection in FIV+ cats.

PMID- 7561520
TI  - Different patterns of deactivation of chemotaxis and haptotaxis of human
      peripheral blood mononuclear leukocytes by soluble and surface-bound attractants.
AB  - Soluble mediators and inducible cell-surface and matrix-bound molecules
      coordinate the cascade of events giving rise to leukocyte emigration. Knowledge
      of the specific mechanisms underlying the attraction of cells into a local site,
      however, remains sketchy. In particular, it is unclear how chemoattractants cause
      rapidly moving immune cells to adhere to the blood vessel wall and to enter
      tissues. Here we show that the neuroendocrine human growth hormone, a
      chemoattractant for monocytes and lymphocytes in vitro, promotes haptotaxis, the
      migration of the cells induced by surface-bound gradients. Combination of soluble
      growth hormone with soluble attractants, RANTES or formyl peptide, deactivates
      the migratory responses, as do combinations of surface-bound growth hormone with
      surface-bound RANTES or formyl peptide. In contrast, exposure of mononuclear
      leukocytes to combinations of soluble chemotactic with surface-bound haptotactic
      gradients of attractants does not deactivate migration. The findings suggest that
      growth hormone may act as haptotactic agent, on the one hand, and that soluble
      attractants do not appear to affect haptotaxis when acting in concert with a
      surface-bound attractant, on the other. This observation may have implications
      for the differential regulation of leukocyte accumulation in the vessel wall at
      systemic and local sites.

PMID- 7561521
TI  - Histamine enhances granulocyte-macrophage colony-stimulating factor and
      interleukin-6 production by human peripheral blood mononuclear cells.
AB  - The effect of histamine on the production of cytokines by subpopulations of
      mononuclear cells was studied. A 3.5-fold increase in the number of myeloid
      colony-forming units (CFU-C) was observed when bone marrow cells were cultured in
      the presence of conditioned medium prepared from nonadherent mononuclear cells
      cultured with 10(-4) M histamine (CM-histamine) compared with phosphate-buffered
      saline (CM-PBS). Using ELISA and radioimmunoassay kits, histamine was found to
      enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear
      cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and
      anti-IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the
      blocking effect in CM-histamine was moderate, indicating enhanced GM-CSF and IL-6
      activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM
      histamine or CM-PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation
      of CM-histamine with H1 and H2 receptor antagonists resulted in complete blocking
      of the histamine-enhanced colony-stimulating activity. We conclude that histamine
      is able to activate human mononuclear cells to generate cytokines such as GM-CSF
      and IL-6 via H1 and H2 receptors.

PMID- 7561522
TI  - Unique patterns of regulation of nitric oxide production in fibroblasts.
AB  - The pathways regulating rat and mouse embryonic and lung fibroblast nitric oxide
      production were analyzed in an attempt to evaluate the potential role of these
      cells in nonspecific host defense and inflammation. Interleukin-1 beta (IL-1
      beta) was found to be the strongest single activator in all types of fibroblasts
      examined. In addition, lipopolysaccharide (LPS) was synergistic with IL-1 beta or
      tumor necrosis factor-alpha (TNF-alpha) in induction of nitric oxide synthesis.
      These patterns of responsiveness are not observed in macrophages and may be
      significant in initiation of early host defense processes, before specific
      interferon-gamma (IFN-gamma)-mediated immune responses have become operative. Rat
      and mouse fibroblasts were also found to produce nitric oxide when primed with
      IFN-gamma and simultaneously treated with IL-1, TNF-alpha, or LPS. The doses of
      IFN-gamma effective in priming fibroblasts for nitric oxide production were as
      low as 1-10 U/ml. Furthermore, effective triggering doses of LPS, TNF-alpha, and
      IL-1 were 10 ng/ml, 100 U/ml, and 0.2 ng/ml, respectively. These results
      demonstrate that fibroblasts are activated more readily to produce nitric oxide
      than interstitial macrophages and may be the major source of this mediator in
      tissues. Immunohistochemical studies demonstrated that fibroblasts are
      heterogeneous with respect to inducible nitric oxide synthase expression with the
      majority of cells not involved in the response. Fibroblasts were also found to be
      distinct from macrophages in their sensitivity to the suppressive effects of
      transforming growth factor-beta, which in fibroblasts inhibited both IFN-gamma
      plus LPS- and IFN-gamma plus TNF-alpha-induced nitric oxide production. At the
      stage of growth crisis, a dramatic increase in nitric oxide production was
      observed in rat fibroblasts in response to IFN-gamma or TNF-alpha that may be
      directly correlated with cellular senescence. Taken together, our data suggest
      that mouse and rat fibroblasts are potential effectors in both IFN-gamma
      dependent and -independent nitric oxide-mediated processes and that the patterns
      regulating nitric oxide metabolism in these cells are distinct from those of
      macrophages.

PMID- 7561523
TI  - Monomeric human IgE evokes a transient calcium rise in individual human
      neutrophils.
AB  - Digital fluorescence calcium imaging was used to investigate and identify the
      primary biological responses of human neutrophils to monomeric immunoglobulin E
      (IgE). Treatment of neutrophils with IgE caused a transient rise in the level of
      intracellular calcium that was inhibited by pertussis toxin. The calcium rise was
      due mainly to release from an intracellular membrane-enclosed store that is also
      sensitive to the chemotactic peptide formyl-Met-Leu-Phe. The IgE-induced calcium
      transient was independent of Fc gamma receptors and of Fc epsilon receptor
      ligation. Our data suggest that the mere binding of IgE to neutrophils is
      sufficient to evoke a biological response without the need for IgE/receptor cross
      linking.

PMID- 7561525
TI  - Identification of an endotoxin and IFN-inducible cDNA: possible identification of
      a novel protein family.
AB  - The response of macrophages to agents such as lipopolysaccharide (LPS) and
      interferon (IFN) includes the transcriptional activation of numerous genes. We
      have used the method of differential screening of a RAW 264.7 macrophage cell
      line cDNA library to isolate and characterize LPS-induced messages. One such
      message, LRG-47, is induced by LPS, IFN-gamma, and IFN-alpha/beta, but not by a
      panel of other cytokines or pharmacological activating agents. LRG-47 is
      homologous to two other IFN-gamma-induced genes, IRG-47 and Mg21. The LRG-47
      sequence is approximately 33% identical and 52% similar to both these putative
      protein products. All three putative proteins, particularly Mg21, bear homology
      to a T cell product, Tgtp, induced by T cell receptor cross-linking. The three
      macrophage-derived proteins share areas of homology with GTP-binding proteins,
      are approximately 415 amino acids in length, and have similar kinetics of
      induction by IFN-gamma. This suggests that these genes may be members of a new
      family of IFN-inducible proteins.

PMID- 7561524
TI  - Regulation of N-formyl-methionyl-leucyl-phenylalanine receptor recycling by
      surface membrane neutral endopeptidase-mediated degradation of ligand.
AB  - Neutrophil responses to alpha-N-formyl-L-Met-L-Leu-L-Phe (fMLF) are modulated by
      inhibitors of surface membrane neutral endopeptidase (NEP), such as
      phosphoramidon (PPAD). Because receptor recycling is presumably required for a
      sustained cellular response, the effect of PPAD on receptor reexpression was
      examined. After down-regulation of surface fMLF receptors by fMLF, PPAD blocked
      the normal reexpression of surface receptors in a manner that was related to the
      time of prior exposure to fMLF. Internalized fML[3H]F was hydrolyzed by NEP at a
      rate comparable to the rate of receptor reexpression at the cell surface,
      suggesting that ligand hydrolysis is rate limiting. To test this hypothesis,
      cells were incubated with fluorescein-labeled formyl-Met-Leu-Phe-Nle-Tyr-Lys at
      15 degrees C. After binding was complete, but before internalization of receptor
      ligand complexes, high-affinity antifluorescein antibody F(ab')2 fragments were
      added and the cells incubated at 37 degrees C for 60 min in the presence of PPAD.
      Under these conditions, the inhibitory effects of PPAD were largely reversed and
      nonimmune F(ab')2 fragments were without effect.

PMID- 7561526
TI  - Protein kinase C and intracellular pH regulate zymosan-induced lysosomal enzyme
      secretion in macrophages.
AB  - Binding of zymosan particles to macrophage beta-glucan receptors has previously
      been shown to trigger exocytosis of preformed lysosomal contents. In the present
      study, the involvement of Ca(2+)-, PKC-, and pH-dependent processes in the
      signaling to macrophage lysosomal secretion by zymosan was investigated. Also,
      the PKC dependence of lysosomal secretion in response to some soluble agents that
      directly alters intracellular pH was considered. Signaling to macrophage
      lysosomal secretion differs from that of many other secretory systems, because an
      elevation of cytosolic Ca2+ did not trigger a large secretory response, nor did
      attempts to reduce cytosolic Ca2+ affect the lysosomal secretory response to
      other stimuli. PKC activation by phorbol diester was also a poor stimulus of
      lysosomal secretion. However, when triggered by zymosan or by soluble stimuli
      raising lysosomal pH, the secretory response could be down-regulated by a prior
      prolonged incubation with phorbol diester. Such treatment also had marked effects
      on the binding and uptake of zymosan particles, the study of which was made
      possible by a novel approach. Furthermore, a synergistic effect on lysosomal
      secretion was obtained when stimuli that elevated lysosomal pH and stimuli that
      activated PKC were combined. This is of likely relevance for the secretory
      response to zymosan particles, a stimulus that both activates PKC and elevates
      lysosomal pH. The secretory response to zymosan was furthermore shown to be
      inhibited by a reduction of extracellular pH or [Na+], conditions that impair
      macrophage extrusion of acid equivalents. Earlier studies using soluble stimuli
      have shown a sensitivity of the secretory response to changes in cytosolic pH. We
      suggest a model in which the lysosomal secretory response to an elevation of
      lysosomal pH (1) is dependent on basal PKC activity and (2) can be enhanced
      further by activation of PKC. We consider PKC activity and elevation of lysosomal
      pH as independent and necessary signals, while cytosolic pH has a modulatory
      effect on some component(s) in the signal transduction pathway or in the
      secretory apparatus itself.

PMID- 7561527
TI  - Execution by crucifixion. History, methods and cause of death.
AB  - Crucifixion, as a method of execution was practiced in many cultures before it
      was outlawed in the Roman Empire by Constantine in 341 C.E., but it has been used
      sporadically since then. Recent archeological excavations of the remains of a
      crucified victim have stimulated studies of the methods used. The theories
      regarding the cause of death as reported in the medical literature are discussed.

PMID- 7561528
TI  - Clinicopathological features of well-differentiated cervical adenocarcinoma with
      abundant mucus secretion.
AB  - Fourteen patients who had cervical adenocarcinoma with abundant mucus secretion
      (stages Ib: 4, IIb: 8, IIIb: 2) were reviewed. Their tumors were clearly
      distinguishable from the majority of cervical adenocarcinomas without abundant
      mucin on the basis of the clinicopathological features. The portio vaginalis
      featured large induration and swelling as well as showing rubber ball-like
      resilience. The surface of tumors showed no ulceration, necrosis, or bleeding,
      even in advanced cases. Colposcopy revealed large glandular openings filled with
      mucus. The initial smear test was negative or suspicious in 11 cases due to the
      abundance of mucus or slight cellular atypia. Even on biopsy findings, five cases
      were diagnosed as normal cervical glands. The diagnosis of cancer had been
      overlooked for six months to one year or more because of negative smears in six
      cases. The final histologic diagnosis was well-differentiated adenocarcinoma
      (endocervical type), including adenoma malignum and mucinous adenocarcinoma.
      Patients with this type of adenocarcinoma had a poor prognosis. It is important
      to keep in mind the distinctive clinical features of adenocarcinoma with abundant
      mucus secretion in order not to miss the diagnosis.

PMID- 7561529
TI  - Analysis of aprotinin on the mean arterial pressure, carotid artery blood flow,
      and hindlimb vascular resistance in the live rat, and pulmonary vascular
      resistance in the isolated perfused rat lung.
AB  - The effects of aprotinin on mean arterial pressure, carotid artery blood flow,
      pulmonary vascular resistance, and systemic vascular resistance have not been
      well documented. Therefore, the responses of aprotinin on the mean arterial
      pressure, carotid artery blood flow and the changes in pulmonary and hindlimb
      vascular resistances were investigated in the rat using ultrasonic flow probe
      analysis, and in two isolated vascular bed preparations. In studies on cardiac
      output using ultrasonic flow analysis, injections of aprotinin, in doses of 70
      7000 KIU intravenously (iv), resulted in no changes in carotid artery ultrasonic
      flow, suggesting no changes in cardiac output. In isolated blood-perfused lung
      studies under conditions of controlled pulmonary blood flow, aprotinin, in doses
      of 7-7000 KIU intra-arterially (ia), caused no significant changes in pulmonary
      arterial perfusion pressure. Aprotinin, in doses of 7-240 KIU, was injected iv
      into the hindquarters perfusion circuit, and hindquarters arterial perfusion
      pressure did not change. Additionally, in the hindquarters perfusion preparation,
      aprotinin, in doses of 70-7000 KIU, ia resulted in no changes in mean arterial
      pressure. The present data demonstrate aprotinin has no significant response in
      MAP, carotid artery blood flow, pulmonary vascular resistance, or hindlimb
      vascular resistance in the rat.

PMID- 7561530
TI  - Adverse drug reactions and outcome of elderly patients on antituberculosis
      chemotherapy with and without rifampicin.
AB  - Antituberculosis (anti-TB) chemotherapy with concomitant administration of
      rifampicin and isoniazid may cause a higher incidence of hepatotoxicity than
      isoniazid alone. We carried out a prospective study of the adverse reactions to
      anti-TB drugs and the clinical outcome in elderly patients on anti-TB
      chemotherapy, to find out whether the omission of rifampicin from standard anti
      TB regime would result in a reduction of adverse reactions and/or mortality
      during anti-TB treatment. Eighty elderly patients (age > 65 years) with TB were
      recruited into the study. They were randomised to receive anti-TB chemotherapy
      consisting of isoniazid, pyrazinamide and ethambutol with or without rifampicin
      for six months. Adverse reactions and mortality occurring during treatment were
      noted. A significantly higher number of patients on rifampicin had elevated liver
      enzymes compared with those not receiving rifampicin. All of these reactions
      responded favorably to adjustment of anti-TB drugs. There was no significant
      difference between the two groups in the incidence of symptomatic adverse
      reactions or mortality during treatment. However, five patients not given
      rifampicin had unsatisfactory resolution radiographically and required additional
      therapy. We conclude that the inclusion of rifampicin in the anti-TB regime
      offers a better therapeutic response but without significantly affecting the
      incidence of adverse reactions or mortality during treatment in elderly patients
      with TB.

PMID- 7561531
TI  - Cardiac accumulation of 125I-labeled monoclonal antibody to atrial natriuretic
      peptide in a rat model of myocardial infarction.
AB  - Atrial natriuretic peptide (ANP) may be an important factor in myocardial
      infarction and subsequent congestive heart failure. In the failing heart, ANP is
      expressed in both the atrium and the ventricle. ANP has now been localized with
      125I-labeled monoclonal antibodies (MAbs) in vivo in a rat model of myocardial
      infarction. Myocardial infarction was produced in 3-month-old Wistar rats by
      ligating the left anterior coronary artery. Two MAbs to rat alpha-ANP accumulated
      in the infarcted left ventricles of treated rats to a significantly greater
      extent (p < 0.01) than in the noninfarcted left ventricles of control rats.
      However, an irrelevant MAb also accumulated to a significantly greater extent in
      infarcted myocardium than in control myocardium. Thus, the accumulation of the
      two MAbs to ANP in infarcted tissue seems to be nonspecific and may be due to
      increased permeability of the injured myocardium.

PMID- 7561532
TI  - Hemorrheologic effects of metabolites of pentoxifylline (Trental).
AB  - Pentoxifylline (Trental) is metabolized by red blood cells and the liver into
      seven metabolites. Metabolites I and V have significant hemorrheologic effects.
      They are both similar to pentoxifylline in their activity on red blood cell
      membrane fluidity. Metabolite I is more active than pentoxifylline in inhibiting
      ADP-induced platelet aggregation. Metabolite V is more active than pentoxifylline
      in inhibiting epinephrine-induced platelet aggregation.

PMID- 7561534
TI  - Medical mystery: Gulf war syndrome.

PMID- 7561533
TI  - Successful simultaneous resection and reconstruction of abdominal aortic aneurysm
      and esophageal cancer.
AB  - A simultaneous resection and reconstruction of abdominal aortic aneurysm (AAA)
      and esophageal cancer was performed on an eighty-year-old Japanese man. In spite
      of his advanced age, preoperative assessments revealed that the general functions
      of the patient were quite satisfactory. An esophagram, endoscopy and CT scan all
      demonstrated the esophageal cancer to be in a relatively early stage without any
      lymph node metastasis, while the CT scan demonstrated an infrarenal type of
      fusiform abdominal aortic aneurysm with a maximum transverse diameter of 7.0 cm.
      A simultaneous resection and reconstruction of both the AAA and esophageal cancer
      was performed on August 8, 1991. First, the operation for AAA was done through a
      retroperitoneal approach, and next, a resection and reconstruction of the
      esophageal cancer was performed with a right thoracotomy and laparotomy using the
      gastric tube as an esophageal substitute. The postoperative course was uneventful
      except for a temporary purulent discharge through the mediastinal drain. The
      patient was discharged on the 56th postoperative day. Therefore, when the general
      conditions are considered to be tolerable for operation, such a simultaneous
      operation may be indicated even inpatients of advanced age by utilizing isolated
      approaches and taking great care.

PMID- 7561535
TI  - A mathematical analysis of a model for tumour angiogenesis.
AB  - In order to accomplish the transition from avascular to vascular growth, solid
      tumours secrete a diffusible substance known as tumour angiogenesis factor (TAF)
      into the surrounding tissue. Neighbouring endothelial cells respond to this
      chemotactic stimulus in a well-ordered sequence of events comprising, at minimum,
      of a degradation of their basement membrane, migration and proliferation. A
      mathematical model is presented which takes into account two of the most
      important events associated with the endothelial cells as they form capillary
      sprouts and make their way towards the tumour i.e. cell migration and
      proliferation. The numerical simulations of the model compare very well with the
      actual experimental observations. We subsequently investigate the model
      analytically by making some relevant biological simplifications. The mathematical
      analysis helps to clarify the particular contributions to the model of the two
      independent processes of endothelial cell migration and proliferation.

PMID- 7561536
TI  - The wrong and right ways to reform Medicare.

PMID- 7561538
TI  - The cryptic error of nondisease: the hidden power of prevalence of disease.

PMID- 7561537
TI  - Physician liability in managed care. A review of four major areas of exposure.

PMID- 7561540
TI  - Coronary heart disease in women. The high prevalance of coronary risk factors and
      the importance of prevention.

PMID- 7561539
TI  - The pill and gynecologic cancer: controversy and mystery prevail.

PMID- 7561541
TI  - Good things don't always come to those who wait.

PMID- 7561543
TI  - Mammography: who, when, and why?
AB  - Breast cancer screening includes two equally important components: mammography
      and routine physical examination. Screening mammography reduces breast cancer
      mortality by about 40% in women over age 50, but its role in younger women
      remains controversial. In roughly 40% of patients, the mammogram will be the only
      screening modality that detects a cancer. Mammography only detects about 90% of
      cancers; it misses 10%. Therefore, a suspicious region detected during a physical
      examination should never be ignored, even if the mammogram is interpreted as
      normal.

PMID- 7561542
TI  - Medicare disaster imminent.

PMID- 7561544
TI  - Visceral abscess in melioidosis.
AB  - A retrospective analysis was done in 81 patients with visceral abscess due to
      melioidosis treated at Khon Kaen Hospital, northeastern Thailand from 1985 to
      1993. The clinical presentations were fever 100 per cent, abdominal pain 39 per
      cent, cough 34.8 per cent, abdominal tenderness 27.5 per cent and palpable mass
      24.6 per cent. The laboratory findings were not diagnostic of the etiology. The
      abscesses were detected by ultrasonography in 97.25 per cent and computed
      tomography 2.25 per cent. The lesions were found in the spleen 72.8 per cent,
      liver 45.7 per cent, kidney 12.3 per cent and prostate gland 2.5 per cent.
      Seventy-six per cent of the patients had diseases in multiple organs (viscera,
      lungs and others). The preliminary diagnoses were fever of unknown origin,
      septicemia and urinary tract diseases in one-half of the cases. Patients
      presenting with fever of unknown origin from an endemic area, like northeastern
      Thailand, should arouse suspicion of melioidosis and search for the organism is
      advised. Diagnostic imaging methods, ultrasonography and computed tomography are
      valuable tools for detection of a solid internal organ abscess.

PMID- 7561545
TI  - Behavior modification in the treatment of obesity: acceptability profiles.
AB  - Seventy obese subjects, after receiving an 8-week group therapy program of
      behavior modification, showed that they had lost weight from fat tissue. There
      were significant decreases of per cent body fat, biceps, subscapular and iliac
      skinfold thickness while maintaining arm muscle area. There were significant
      decreases of both systolic and diastolic blood pressure during the program. The
      acceptability profiles of heart rate, liver and renal function test, fasting
      blood sugar, uric acid, serum iron, total iron binding capacity, minerals,
      electrolytes, hematological and lipid profiles were within normal limits before
      and after the treatment. The obese subjects rated the behavior modification
      program as more effective and indicated helpfulness of concepts, information and
      techniques of the program.

PMID- 7561546
TI  - A summer camp for childhood obesity in Thailand.
AB  - The results of a 4-week summer camp for childhood obesity were reported. Twenty
      one children with moderate to severe obesity, aged between 8-13 years, joined the
      program. Dietary restriction during the official hours and dietary self-control
      at home were implemented throughout the program. Exercise, swimming and group
      therapy were also implemented throughout the program. Weekly sight-seeing outside
      the camp was very interesting for the participants. After the program, all
      participants had lost weight which was about 5 per cent of their initial weight.
      Most of the weight loss was due to loss of body fat but not lean body mass. No
      complications occurred during the program. The 4-week summer camp is then
      practical for initiating weight loss for obese children. Long-term follow-up
      which is underway will be reported later.

PMID- 7561547
TI  - Operative wound infection.
AB  - Wound infection is the commonest complication after operation and frequently
      gives rise to complex problems which may be very difficult to manage and
      prevention is most desired. For successful prevention, one must understand the
      pathogenesis of wound infection and follow strictly the regulations or
      precautions of aseptic and operative techniques to minimize contamination which
      consequently will reduce the incidence of post operative wound infection.

PMID- 7561548
TI  - Microsporidium: modified technique for light microscopic diagnosis.
AB  - Microsporiodosis caused by Enterocytozoon bieneusi is one of the opportunistic
      infections in HIV positive patients with chronic diarrhea. The organism is
      difficult to diagnose because of its small size, previously the diagnosis of this
      infection relied on identification of the organism under electron microscope.
      Until recently, the spores of this organism in stool specimens could be seen
      under light microscope by using various staining techniques. In this study, the
      modified trichrome staining technique was used to identify microsporidia spores
      with characteristic red belt-like stripes. Less time and less reagent are
      required by this modified technique than the conventional method.

PMID- 7561550
TI  - Traumatic abdominal wall hernia.
AB  - Two cases of traumatic abdominal wall hernia, produced by impaction of the
      motorcycle handlebars, are reported. The mechanism of injury, clinical and
      radiologic diagnosis are discussed. Because of the high incidence of other
      associated intraabdominal injuries, early exploration and repair through a
      midline incision is advocated. Adequate debridement and solid repair of fascial
      planes with non-absorbable sutures are required to prevent recurrence. Primary
      closure of the musculofascial defect was performed in both reported cases and the
      recovery was uneventful.

PMID- 7561549
TI  - CA 50: a tumor marker for gastrointestinal malignancies.
AB  - Efforts to find the ideal tumor marker, together with the advanced knowledge of
      the carbohydrate expression by cancer and the development of monoclonal antibody
      technology have facilitated the generation of many new tests used in clinical
      oncology. CA 50, a novel cancer-associated carbohydrate marker, is detected by
      the C 50 antibody that has been obtained by immunization of mice with a human
      colorectal adenocarcinoma cell line. This antibody that defines CA 50 reacts with
      both the afucosyl form of sialylated Lewis(a) carbohydrate moiety and sialylated
      Lewis(a) moiety which is also the antigenic epitope in the CA 19-9 assay. CA 50
      is not organ-specific and its elevated levels in serum can be observed in a
      variety of malignancies, especially gastrointestinal cancers. In contrast to CA
      19-9, high CA 50 levels can also be seen in malignant tumors outside the
      digestive tract. The expectation, that CA 50 might be positive in the Lewis
      negative patients who cannot synthesize CA 19-9, is supported by the
      histoimmunologic study. However, in serum determination close correlation between
      CA 50 and CA 19-9 has been observed even in patients who have Lewis negative
      phenotype. In clinical application, CA 50 is marginally beneficial for the
      diagnosis, but very useful for the follow-up of patients with pancreatic cancers.
      It gives results rather similar to CA 19-9. Moderately high serum levels of CA 50
      can also be seen in benign hepatobiliary diseases, especially in jaundice cases.
      Therefore, this should be considered in order to obtain the most advantage of the
      marker. For other gastrointestinal cancers, CA 50 in combination with other
      previously defined markers may give additional information for the evaluation of
      some patients with colorectal, biliary, or gastric cancers. At present, there are
      many new emerging tumor markers used in clinical oncology. Increasing our
      knowledge about these markers, their capabilities and limitations will enable us
      to use them effectively in the evaluation of cancer patients.

PMID- 7561551
TI  - Lipoblastic meningioma: a light and electron microscopic study.
AB  - A patient with intracranial lipoblastic meningioma in the right frontal lobe is
      reported. The tumor was entirely made up of vacuolated cells. The nature of this
      rare neoplasm has been verified by light and electron microscopic studies.

PMID- 7561552
TI  - Treatment of various movement disorders with botulinum A toxin injection: an
      experience of 900 patients.
AB  - A prospective open study of botulinum toxin A treatment for patients with various
      movement disorders at Siriraj Hospital, Mahidol University was analysed to
      evaluate its efficacy. The grand total of 900 patients comprised of a) 592
      patients (65.78 per cent) with hemifacial spasm; b) 92 patients (10.22 per cent)
      with occupational cramp; c) 79 patients (8.78 per cent) with blepharospasm and
      Meige syndrome; d) 72 patients (8.00 per cent) with spasmodic torticollis; e) 19
      patients (2.11 per cent) with hemidystonia and generalised dystonia; f) 11
      patients (1.22 per cent) with spasmodic dysphonia; g) 10 patients (1.11 per cent)
      with spastic hemiparesis; and h) 25 patients (2.78 per cent) with miscellaneous
      group (i.e. tics, Gilles de la Tourette, facial myokimia, benign fasciculation,
      etc.). The results of treatment for hemifacial spasm were classified as excellent
      in 486 patients (82.09 per cent), moderate improvement in 60 patients (10.14 per
      cent), mild improvement in 39 patients (6.59 per cent) and no improvement or
      worse in 7 patients (1.18 per cent). There were complications of mild transient
      facial weakness in 50 patients (8.45 per cent) and mild ptosis in 12 patients
      (2.02 per cent). The effect of botulinum toxin treatment lasted 3-6 months. In
      occupational cramp and spasmodic torticollis the good response rate was around
      two-thirds of all patients, whereas, blephalospasm, spasmodic dysphonia, spastic
      hemiparesis and tics responsed in 79-88 per cent of the patients. Botulinum toxin
      A injection is thus a simple, safe, and effective out-patient treatment for
      patients with various kinds of movement disorders but it is a costly therapy.

PMID- 7561553
TI  - Surgery for intractable vertigo: Chiang Mai experience.
AB  - If medical therapy fails (6-12 months or more), careful consideration of surgical
      therapy should be followed with; the patient's hearing, severity of symptoms,
      age, and occupation. Cochleosacculotomy is reserved for elderly Meniere's
      patients with poor health, poor hearing and good vestibular function.
      Endolymphatic sac shunt should be considered as the first procedure for disabled
      Meniere's patients with aidable hearing and may also be used in those patients
      with bilateral Meniere's disease. Retrolabyrinthine vestibular nerve section
      (RLVNS) is indicated for patients with disabling vertigo and normal or aidable
      hearing. It could be done for all peripheral vertigo and for failed endolymphatic
      sac procedure. A destructive procedure, such as labyrinthectomy, should be a
      procedure of choice in a patient who presents with peripheral incapacitating
      vertigo and nonserviceable hearing loss in the solely affected ear. Again,
      patients with failed cochleosacculotomy, endolymphatic shunt then go on to
      receive either labyrinthectomy or RLVNS, based on residual hearing. To obtain a
      satisfactory surgical result, the surgeon must be precise in selecting the
      patient with the right disease at the right time.

PMID- 7561555
TI  - Study urinary stone in Buri Ram province by portable ultrasound.
AB  - Prevalent rate of urinary stone surveyed by ultrasound in 15 district hospitals
      of Buri Ram Province was 3.1 per cent. The positive predictive value compared
      with X-rays plain KUB was 75 per cent.

PMID- 7561556
TI  - The usage of Andrographis paniculata following Extracorporeal Shock Wave
      Lithotripsy (ESWL).
AB  - One hundred consecutive cases with renal stones less than 3 cm in size and normal
      renal function underwent ESWL from January to March 1994. Out of these, 50 were
      given Andrographis paniculata tablets (250 mg), 4 tablests tid, 25 were given
      cotrimoxazole 2 tablets bid and 25 received norfloxacin 200 mg bid, started
      immediately after ESWL and continued for 5 days. All tolerated the treatment well
      and none had complications. At one month follow-up, pre- and post-ESWL pyuria,
      hematuria and proteinuria among the Andrographis paniculata group were 84, 58,
      72, 40, 52, 22 per cent; the cotrimoxazole group 88, 64, 84, 64, 56, 44 per cent
      and the norfloxacin group 92, 56, 72, 40 per cent and 56, 28 per cent
      respectively. The results showed that post ESWL pyuria and hematuria in patients
      receiving Andrographis peniculata were reduced to 0.69 and 0.55 time of pre ESWL
      value. We think that this herbal medicine is beneficial in the treatment of post
      ESWL urinary tract infection. Besides the herbal drug given to eighteen
      previously sulfa sensitized patients resulted in no allergic reaction.

PMID- 7561554
TI  - A comparison of two short course tuberculosis chemotherapy regimens, both using
      Rifater during an intensive phase, with a 3 year follow-up.
AB  - Tuberculosis is still a major public health threat in Thailand. The introduction
      of a short course of chemotherapy at national level might help reduce the
      magnitude of the problem. In order to assess the efficacy and toleration of two
      different regimens of chemotherapy under field conditions, a comparative
      clinically controlled trial was conducted at the Central Chest Hospital in
      Nonthaburi, Thailand. From January 1988 to August 1990, 199, newly diagnosed,
      untreated, sputum positive tuberculosis patients were allocated randomly to two
      treatment groups; in Group A, 97 patients received Rifater daily for the first 2
      months, followed by Rifinah daily for 4 months (2 Rifater/4 Rifinah). In Group B,
      102 patients received Rifater supplemented by ethambutol daily for the first 2
      months followed by thiacetazone and isoniazid daily for 6 months (2 Rifater EMB/6
      HT.) Treatment results were very satisfactory in both groups. At the end of
      treatment conversion rates were 100 per cent in Group A, and 99 per cent in Group
      B. After a period of 36 months following completion of treatment, relapse rates
      of 3 per cent for Group A and 4 per cent for Group B were observed. Adverse
      reactions were minimal in both groups, but acne formation and gastrointestinal
      symptoms were noticed more in Group B, suggestive of thiacetazone side effects.
      This study shows that, the 6-months regimen is as effective as the 8-months
      regimen. Although the 8-months regimen is cheaper, it causes more
      gastrointestinal disturbance and skin reaction which might led to less patient
      compliance and result in a lower cure rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561557
TI  - Thrombolytic therapy in 1995.
AB  - In summary, the amount of research in the field of thrombolysis done in patients
      with acute myocardial infarction has shown the enormous benefit not only for
      mortality but other cardiovascular events. Its benefit over other non cardiac
      conditions are accumulating. Several large-scale studies are underway and
      expected to give us answers for which conditions will benefit from thrombolytic
      therapy.

PMID- 7561558
TI  - Thrombotic thrombocytopenic purpura (TTP): 4 case reports and review of the
      literature.
AB  - From 1987 to 1992 we found 4 cases of TTP in Chonburi Hospital. All were female,
      age range was 19-43 years. The criteria for making the diagnosis were based on
      the findings of MAHA (3 cases), thrombocytopenia (4 cases), neurological
      alternation (4 cases), fever (4 cases) and renal involvement (3 cases). Treatment
      consisted of plasma infusion, corticosteroid, ASA and dipyridamole. Two patients
      whose treatment began within 48 hours after admission survived, whereas, the
      other two whose treatment began 3 days and 6 days after hospitalisation died.
      Review of the literature concerning the clinical features, pathogenesis and
      current treatment was performed. The importance of giving early diagnosis and
      treatment to improve the survival rate in this disease is also emphasized. TTP
      has high mortality so it is important to make a correct diagnosis and give prompt
      treatment. The best treatment is plasmapheresis. The other forms of treatment are
      plasma infusion, steroid, antiplatelet drugs, immunosuppressive drugs and
      splenectomy.

PMID- 7561559
TI  - Diencephalic epilepsy resembling pheochromocytoma: a first reported case in
      Thailand.
AB  - A 31 year old hypertensive patient suffered from a fluctuation of blood pressure.
      Pheochromocytoma was suspected because of the clinical history, and extremely
      labile blood pressure but did not respond to therapy with alpha adrenergic
      blocking agent and normal excretion rates of catecholamine and vanilly mandelic
      acid (VMA). An enlarged left adrenal gland from computerized tomographic scan was
      found. So left adrenalectomy was performed and the result was consistent with
      cortical adrenal hyperplasia. Fluctuation of blood pressure still occurred after
      surgery with the symptoms of epigastric oppression and focal epileptic attack of
      the left arm. Epileptic potential waves were seen during hyperventilation from
      electroencephalogram but showed normal magnetic resonance imaging computerized
      tomographic scan of the brain. Diencephalic epilepsy was diagnosed and treated
      with anticonvulsant (carbamazepine) and eventually all of the symptoms including
      labile blood pressure subsided.

PMID- 7561560
TI  - Post-traumatic empyema thoracis in blunt chest trauma.
AB  - Three out of 42 patients who had isolated blunt chest injury requiring closed
      tube thoracostomy developed post-traumatic empyema thoracis. All of them were
      treated by thoracotomy and evacuation of the infected fluid with multiple chest
      tube drainage. Cultures of the pleural fluid grew Staphylococcus aureus in these
      3 patients. Univariate analysis was performed by using Fisher's exact test which
      revealed the significance of age in association with the development of empyema
      thoracis. Multivariate analysis was performed by using Logistic Regression.
      Although no statistical significance was observed, the analysis revealed that the
      risk of empyema thoracis increased in elderly patients and in patients who had
      prolonged placement of thoracostomy tube. Intensive pulmonary care in elderly
      patients who sustained chest injury and early removal of thoracostomy tube is
      recommended in order to prevent the development of empyema thoracis.

PMID- 7561561
TI  - Prognostic factors in patients hospitalized with pneumonia.
AB  - Prognostic factors in patients hospitalized with pneumonia was analysed from 526
      non-immunocompromised host patients who were admitted to the Medical Department
      of Chulalongkorn Hospital during the period of January 1987 to December 1991. The
      overall mortality was 30.5 per cent. The causes of death were 12.7 per cent of
      progressive or uncontrolled pneumonia, 10.1 per cent of underlying diseases and
      7.2 per cent of complications of assisted ventilation. Patients aged 60 or older
      than 60 years, abnormal host, mental status changes, respiratory failure, shock,
      bronchopneumonia, g-ve pneumonia had significantly higher mortality than those
      who had no such conditions. Patients with pneumonia who had respiratory failure
      and shock had highest mortality at 70.2 and 85.1 per cent, respectively. Our
      study indicated that the presence of pleuritic chest pain and pleural effusion
      had a favourable effect on the outcome.

PMID- 7561562
TI  - Effect of aloe vera gel to healing of burn wound a clinical and histologic study.
AB  - In a study of twenty-seven patients with partial thickness burn wound, they were
      treated with aloe vera gel compared with vaseline gauze. It revealed the aloe
      vera gel treated lesion healed faster than the vaseline gauze area. The average
      time of healing in the aloe gel area was 11.89 days and 18.19 days for the
      vaseline gauze treated wound. Statistical analysis by using t-test and the value
      of P < 0.002 was statistically significant. In histologic study, it showed early
      epithelialization in the treated aloe vera gel area. Only some minor adverse
      effects, such as discomfort and pain were encountered in the 27 cases. This study
      showed the effectiveness of aloe vera gel on a partial thickness burn wound, and
      it might be beneficial to do further trials on burn wounds.

PMID- 7561563
TI  - Carpal tunnel syndrome during pregnancy: prevalence and blood level of
      pyridoxine.
AB  - The prevalence of CTS in third trimester pregnant women in the study in 28 per
      cent. With the use of NCS it was able to detect nearly 80 per cent of them who
      had no symptoms or signs. There was no association between the level of vitamin
      B6 or B6 deficiency and CTS. Since CTS may result in a permanent disability if
      undiagnosed or left untreated it is essential to make an early diagnosis and
      treat it especially older women and those who are edematous.

PMID- 7561564
TI  - The surgical treatment of atrial myxomas: clinical experience in 6 patients.
AB  - Six patients from 17 to 73 years of age (mean age 37.3 years) underwent excision
      of atrial myxomas between November 1990 and August 1994 at Maharaj Nakorn Chiang
      Mai Hospital, Chiang Mai University, Chiang Mai. There were 4 females and 2
      males. All the tumors were located in the left atrium, no right atrial or
      ventricular tumors were identified. Four patients presented with congestive heart
      failure, one with tachyarrhythmia, and one with cerebral embolism. Symptoms were
      present from 1 to 80 months before operation. Physical examination revealed
      murmur of mitral insufficiency in 4 patients, bibasilar rales in 2 patients and
      peripheral edema in 2 patients. Electro-cardiographic analysis demonstrated that
      4 of 6 patients were in sinus rhythm and atrial fibrillation in the remaining
      patients. All the patients were diagnosed by two-dimensional echocardiography.
      The myxomas were successfully removed in all patients utilizing extracorporeal
      cardiopulmonary bypass without hospital mortality. In the early follow-up period
      (2-27 months), 5 patients are in New York Heart Association class I and one
      patient is in class II. No recurrent myxomas have been identified clinically in
      any patient. In this report, good results were obtained by simple excision of the
      tumor. Long-term clinical and echocardiographic follow-up is recommended since
      late recurrence, although rare, has been reported.

PMID- 7561565
TI  - Closed intramedullary nailing for femoral shaft fracture in Ratchaburi Hospital.
AB  - Forty-four patients with 44 femoral shaft fractures were treated by AO
      interlocking nail technique at Ratchaburi Hospital. All cases were comminuted,
      segmental or rotational unstable fractures caused by traffic accidents. All
      patients had more than 90 degrees flexion of the knee within 2 weeks and resumed
      full range of motion of the knee within 2 months post-operatively. There were no
      serious complications found in the period of 29 months follow-up. We conclude
      that the closed interlocking nail is one of the treatments of choice for
      comminuted, segmental or rotational unstable femoral shaft fractures.

PMID- 7561566
TI  - Antineoplastic-associated colitis in Chulalongkorn University Hospital.
AB  - Clostridium difficile is well known for causing pseudomembranous colitis. Most
      cases are associated with the use of antimicrobial agents. Non-antibiotic
      associated colitis has rarely been reported. The causes of colitis are related to
      dietary changes, anesthesia, uremia, and various non-antibiotics medications,
      especially antineoplastic agents. Most responsible antineoplastics in previous
      reports are methotrexate and 5FU. From July 1993 to August 1994, 34 cancer
      patients developed acute diarrhea after chemotherapy. Six cases hd chemotherapy
      associated colitis. All patients presented with moderate to severe diarrhea and
      demonstrable C.difficile toxin in fecal specimens and did not receive any
      antibiotics before the onset of diarrhea. Premier enzyme immunoassay (EIA) was
      used for toxin A assay because it is easy to perform and needs no special tissue
      culture laboratory facility. Data from multicenters studies have shown good
      sensitivity and specificity of the test. We found documented antineoplastics
      associated colitis, 7 episodes from 35 episodes of diarrhea (20.0%) that had been
      tested with EIA for toxin A. Five of 6 episodes were 5FU related. One patient had
      2 episodes of antineoplastic associated colitis with the same chemotherapy
      regimen. The underlying malignancies were GI malignancies in 3 of 6 patients. In
      conclusion, moderate to severe diarrhea in cancer patients after chemotherapy
      should alert the physician to be aware of a potential fatal complication caused
      by C.difficile infection. True incidence has been undoubtedly masked by
      concomitant antimicrobial treatment and physician unawareness. Early recognition,
      discontinuation of chemotherapy and prompt treatment should be done to reduce
      morbidity and mortality of this disease.

PMID- 7561567
TI  - Chronic subdural hematoma three cases treated by a general surgeon.

PMID- 7561568
TI  - Pleomorphic lipoma in the middle mediastinum.
AB  - Mediastinal pleomorphic lipoma was found in a 63-year-old Thai male who presented
      with problems of chronic cough, dyspnea and dysphagia for 1 year. CT and MRI
      studies revealed a well-circumscribed mass in the middle mediastinum. Thoracotomy
      was performed and excision of the tumor was done completely. The pathological
      features of the tumor were typical of pleomorphic lipoma. While lipomas are
      common tumors in the mediastinum, liposarcomas are rare and there has been no
      reported case of mediastinal pleomorphic lipoma before. Differential diagnosis of
      liposarcoma was very important in this case due to different clinical courses and
      prognoses.

PMID- 7561570
TI  - Goiter in Thai schoolchildren: study in Hat Yai, southern Thailand.
AB  - Examination for goiter was performed in 6,035 schoolchildren (2,899 girls, 3,136
      boys), aged 8-17 years, from primary and secondary schools in Hat-Yai
      municipality, Songkhla province. Goiter was detected in 355 children (combined
      prevalence 6%; 232 or 8% in girls, 123 or 4% in boys). Of the 355 children with
      goiter, 214 (60%; 148 girls, 66 boys) participated in the study, and had blood
      drawn for free thyroxine (FT4), triiodothyronine (T3), thyroid stimulating
      hormone (TSH), and thyroid antibodies. All had urine collected for iodine
      excretion. The diagnoses of goiter were as follows: simple goiter in 192 (89.8%;
      129 girls, 63 boys); juvenile autoimmune thyroiditis in 18 (8.4%; 16 girls, 2
      boys); Graves' disease in 2 girls (0.9%); thyroid adenoma in 1 boy (0.45%), and
      ectopic thyroid in 1 girl (0.45%). Acquired hypothyroidism was found in 4 out of
      18 children with juvenile autoimmune thyroiditis (22.2%). Iodine deficiency
      disorder was not evident in children examined shown by high urinary iodine
      excretion of more than 50 mcg/gm creatinine (mean 298, range 70-630). In
      conclusion, simple goiter is a common occurrence in children and adolescents in
      Southern Thailand. Juvenile autoimmune thyroiditis should be identified and
      differentiated from simple goiter as it is the most common cause of acquired
      hypothyroidism. Iodine deficiency is not evident in Southern Thailand, at least
      in the urban areas of a large city.

PMID- 7561569
TI  - Fatal hemorrhage from additional primary esophageal squamous cell carcinoma in a
      patient previously having primary bronchogenic adenocarcinoma.
AB  - A unique occurrence is presented of additional primary epidermoid carcinoma of
      the esophagus with fatal bleeding into the upper digestive tract after 3 years of
      diagnosis of primary bronchogenic adenocarcinoma of an 81-year-old Thai man. The
      primary bronchogenic adenocarcinoma was surgically removed and followed by
      radiotherapy and chemotherapy without evidence of tumor recurrence at autopsy.
      The epidermoid carcinoma of the lower one-third of the esophagus metastasized to
      the pleura of the remaining right lung. There was no complaint of dysphagia.
      Outward extension through the esophageal wall rather than intraluminal protrusion
      of the squamous cell carcinoma was thought to result in the absence of dysphagia.
      Although it is uncommon physicians should be aware of the occurrence of multiple
      neoplasms.

PMID- 7561571
TI  - Ofloxacin otic solution as treatment of chronic suppurative otitis media and
      diffuse bacterial otitis externa.
AB  - Pseudomonas aeruginosa, Diphtheroid bacilli, Staphylococcus aureus were the major
      causes of diffuse bacteria otitis externa and chronic suppurative otitis media.
      This study showed that 0.3 per cent ofloxacin used for 2 weeks gave good clinical
      and bacteriological control of chronic suppurative otitis media and diffuse
      bacterial otitis externa without significant side effects.

PMID- 7561572
TI  - Multiplex PCR to detect the dystrophin gene deletion in Thai patients.
AB  - We have demonstrated the usefulness of the multiplex PCR to directly detect the
      dystrophin gene mutation. Prenatal diagnosis and confirmation of clinical
      diagnosis of DMD/BMD via non invasive technique are now possible. Nine DMD and
      one BMD patients were tested. Five DMD patients demonstrated deletion. Thus, this
      multiplex PCR could detect deletion in approximately 50 per cent of DMD/BMD Thai
      patients. Eighty per cent of the deletions were in the distal part, whereas, 20
      per cent were in the proximal part. We are planning to establish other molecular
      techniques such as linkage analysis, cDNA hybridization and immunostaining of
      dystrophin protein to improve a mode of diagnosis and management of DMD/BMD
      patients in the Thai community.

PMID- 7561573
TI  - Trial of transdermal nicotine patch in smoking cessation.
AB  - In order to evaluate the efficacy of the transdermal nicotine patch, 37 persons
      who wore the patches (group 2) were compared with 40 persons who attended an
      organized smoking cessation program (group 1). At 1 month, 8 persons of group 2
      (21.62%) and 22 persons of group 1 (55%) were able to stop smoking. At 3 months,
      8 persons of group 2 (21.62%) and 17 persons of group 1 (42.5%) were still
      abstinent. At 6 months, 7 persons of group 2 (18.9%) and 14 persons of group 1
      (35%) were able to stop smoking. At 12 months, 5 persons of group 2 (13.5%) were
      able to maintain their abstinence. Counselling and follow-up support are needed
      to maintain abstinence.

PMID- 7561574
TI  - Austin Moore hip prosthesis replacement in Ratchaburi Hospital.
AB  - From 1992 to 1994, eighty-two patients with 82 displaced femoral neck fractures
      were operated on with Austin Moore prosthesis replacement at the Department of
      Orthopedics, Ratchaburi Hospital. There were 31 males and 51 females, their mean
      age was 68.4 years (range: 21-91 years). Sixty-two patients were seen at the
      average of 12.36 months' follow-up (range: 6-31 months). The clinical result was
      excellent 51.61 per cent, good 25.81 per cent, fair 11.29 per cent and poor 11.29
      per cent. There were three cases of superficial wound infection, two cases of
      minor fissures or fractures during surgery, and two cases of stem loosening. Two
      patients died within 2 weeks post-operatively due to recurrent myocardial
      infarction.

PMID- 7561575
TI  - Prediction of post-thaw sperm motility and sperm cryosurvival rate using the pre
      freeze sperm parameters.
AB  - To determine the relationships between pre-freeze semen variables and
      cryosurvival rate and post-thaw motility and examine whether they have any
      predictive value for the cryosurvival rate and post-thaw sperm motility,
      conventional semen analysis, supravital staining for sperm viability and hypo
      osmotic swelling test were performed on 50 semen samples before cryopreservation.
      Thawed semen samples were examined for post-thaw sperm motility and cryosurvival
      rate. Significant correlations were observed between post-thaw sperm motility and
      several pre-freeze semen variables, such as, hypo-osmotic swelling test, pre
      freeze sperm motility and sperm viability. In a stepwise regression analysis, an
      accurate prediction of post-thaw sperm motility (R = 0.826) was obtained using a
      multiple regression equation incorporating 3 variables including hypo-osmotic
      swelling test, pre-freeze sperm motility and sperm concentration. In conclusion,
      a set of criteria have been identified that accurately predicts post-thaw sperm
      motility and which place particular emphasis on hypo-osmotic swelling test.
      Conventional semen analysis and hypo-osmotic swelling test are simple and
      effective assays for the prediction of post-thaw motility.

PMID- 7561576
TI  - Determinants of multiple pregnancies in in vitro fertilization other than number
      of transferred embryos.
AB  - The aim of this study is to assess the many different parameters involved in the
      incidence of multiple pregnancies, such as maternal age, stimulation,
      endometrium, receptivity and the quality of the transferred embryos. During a 3.5
      year period, 86 pregnancies were recorded in our IVF unit. A single gestational
      sac was identified by early ultrasonography in 67 patients, while in 19 others,
      multiple sacs were noted. Patient characteristics, treatment cycles and
      embryology results were similar in the two groups. When the number of transferred
      embryos was kept similar in both groups, EIR was found to be a valuable
      prognostic determinant for multiple pregnancies in IVF.

PMID- 7561577
TI  - Intraoperative transesophageal echocardiography: preliminary experience at
      Siriraj hospital.
AB  - In order to evaluate the result of intraoperative TEE monitoring for
      cardiothoracic surgery, 113 patients were involved in this study. They included
      65 males and 48 females, with an average age of 48.8 +/- 16.6 years, ranging from
      10 to 74 years. The pre-operative diagnoses consisted of 41.6 per cent coronary
      artery disease, 34.5 per cent valvular disease, 12.4 per cent congenital heart
      disease, 8 per cent aortic aneurysm or aortic dissection, and 3.5 per cent of
      miscellaneous. The TEE appeared to provide accurate information by beating to
      changes in the left ventricular preload and contractility in all patients. The
      severity of valvular dysfunction, intracardiac air/mass, Swan Ganz catheter
      position, sites of congenital heart defect and aortic dissection were either
      assessed or reconfirmed during the operation. The ease of TEE technique was
      satisfactory, since unsuccessful attempt was observed in only 1.8 per cent. One
      patient died from rupture of thoracic aortic dissection which was related to TEE
      probe insertion. These data suggest the favorable result of intraoperative TEE as
      a valuable tool for monitoring in cardiothoracic surgery. Although the technique
      is simple, special precaution must be observed for patients suffering from acute
      aortic dissection.

PMID- 7561578
TI  - Body temperature in medical inpatients: what is the meaning of fever?
AB  - A study which aimed to determine the appropriate body temperature level for
      diagnosing fever was conducted in 160 medical inpatients admitted to the medical
      wards of Chulalongkorn University Hospital. Both objective and subjective
      findings were used as criteria for fever. This study demonstrates that the most
      appropriate cutoff levels for oral, axillary and rectal body temperature
      measurement in clinical practice are 37.8, 37.5 and 38.3 Celsius respectively.
      The oral body temperature is better than the axillary and rectal body temperature
      for fever diagnoses in medical inpatients.

PMID- 7561579
TI  - Calcified cystic pituitary prolactinoma.
AB  - An unusual cystic pituitary prolactinoma in a 20-year-old man is described. The
      tumor was roentgenographically calcified. Ultrastructurally, the calcium deposits
      were found within the cytoplasm of tumor cells, extracellular spaces and blood
      vessels. The mechanism of intratumoral calcification is discussed in relation to
      degeneration of neoplastic cells and reparative process.

PMID- 7561581
TI  - Pneumonia in mechanically ventilated patients in Nan Hospital intensive care
      unit.
AB  - A study on ventilator-associated pneumonia was done in the I.C.U., Nan Hospital
      from April 1991 to March 1992. Of the 536 patients, 40 had pneumonia (7.5%). One
      half of the cases with pneumonia were on mechanical ventilation for 3-7 days. The
      incidence rate of pneumonia was 17.5, 6.5, 2.5 and 0 per cent in paediatric,
      medical, surgical and gynaecologic patients. Nine patients died of pneumonia. Low
      birth weight was the commonest predisposing factor of death along with prolonged
      ventilatory support and resistant bacteria. Breaching of aseptic and nursing care
      techniques was also observed.

PMID- 7561580
TI  - Chorangiopagus parasiticus twins: case report.

PMID- 7561582
TI  - Bacterial peritonitis associated with peritoneal dialysis.
AB  - A retrospective study on bacterial peritonitis was done in patients undergoing
      peritoneal dialysis in Nan Hospital from January 1990 to June 1993. There were
      154 patients. The average dialysis cycle was 52 and duration of dialysis was 50
      hours. Bacterial peritonitis confirmed by positive culture was found in 13
      patients (8.4%). All infected patients had over 48 dialysis cycles and had the
      peritoneal catheter repositioned. The predominant bacteria were Pseudomonas
      aeruginosa and Klebsiella pneumoniae. One patient died of the infection.
      Meticulous care is needed to lower the risk of this complication.

PMID- 7561583
TI  - Needlesticks and cuts with sharp objects in Siriraj Hospital 1992.
AB  - A study on needlesticks and cuts with sharp objects was done by a set of
      questionnaires in Siriraj Hospital in March 1992. The response rate of 3,600 sets
      of questionnaires was 80.8%. The recalled incidence rate of injuries in the
      previous 6 months was 51.5%. Needlesticks were the commonest accident followed by
      cuts by broken glass and medical equipment respectively. Bore needles were the
      most important cause of injury. Recapping and improper disposal of used needles
      were prevalent. With the same incidence rate of such injuries, it was estimated
      that 5.9 persons will be HIV infected annually in Thailand.

PMID- 7561584
TI  - Universal precautions: knowledge, compliance and attitudes of doctors and nurses
      in Thailand.
AB  - A study on the knowledge, compliance and attitudes of doctors and nurses on
      "universal precautions" (U.P.) was done by questionnaire in April 1993. Four
      hundred and sixty-nine doctors and 4,554 nurses from 35 hospitals throughout
      Thailand responded. Almost all doctors and nurses understood the definition of
      U.P.. The latter were correctly applied in less than half of the personnel. A
      significant number of doctors and nurses required HIV screening tests and
      isolation of patients with HIV infections. Most doctors and nurses knew that
      sharp injuries were the most important cause of acquiring HIV infection in health
      care settings. Those who are more vulnerable to injury would take more
      precautions. Up to a quarter of doctors and nurses did not fully understand how
      to use protective barriers properly. The practice of handwashing needs to be
      improved. Both doctors and nurses were willing to take care of HIV infected
      patients. They supported the application of U.P. as a safety measure. Welfare
      support for health-care workers who have contacted HIV at work is also expected.

PMID- 7561585
TI  - Compliance with universal precautions by emergency room nurses at Maharaj Nakorn
      Chiang Mai Hospital.
AB  - Compliance with universal precautions (UP) by emergency room nurses in Maharaj
      Nakorn Chiang Mai Hospital was studied between August 1, 1992 and November 30,
      1992. Data were gathered from observation, questionnaires, and focus group
      discussion. During a period of 3 months, 23 registered nurses and 17 practical
      nurses were observed during performing 509 UP-specific nursing procedures.
      Results showed a low rate of compliance with universal precautions among
      emergency room nurses. Aside from handwashing, the compliance of registered
      nurses was significantly higher than that of the practical nurses: 58% and 18%,
      respectively (P < 0.05). The most common protocol violations involved the use of
      barrier precautions. Gloves were the only protective attire that were worn while
      carrying out nursing interventions; other protective attire was completely
      ignored. The results also indicated that some nurses, both registered and
      practical, still recapped needles and demonstrated low rates of compliance with
      recommended handwashing procedures. In addition, they were more likely to apply
      the recommended universal precautions for patients with known HIV infection. The
      reasons for not using protective attire were similar for both registered and
      practical nurses i.e.: supplies not available, insufficient time, discomfort,
      inconvenience, habit, believing UP were not necessary, and concerns about
      patients' feeling and about nurses' own appearance. The findings also indicated
      that many emergency room nurses did not understand the implication of the UP for
      practice and had never participated in an inservice education programme related
      to UP.

PMID- 7561586
TI  - Guidelines for prevention and management of needlestick. The Hospital Infection
      Control Group of Thailand.

PMID- 7561587
TI  - Guidelines for infection control in dental units. The Hospital Infection Control
      Group of Thailand.

PMID- 7561588
TI  - Guidelines for prevention of nosocomial enteric infection. The Hospital Infection
      Control Group of Thailand.

PMID- 7561589
TI  - Guidelines for the use of protective barriers in clinical practices. The Hospital
      Infection Control Group of Thailand.

PMID- 7561590
TI  - Guidelines for a policy on the use of antiseptics and disinfectants. The Hospital
      Infection Control Group of Thailand.

PMID- 7561591
TI  - Guidelines for the choice of disposable and reusable medical equipment. The
      Hospital Infection Control Group of Thailand.

PMID- 7561593
TI  - Guidelines for infection control in health personnel. The Hospital Infection
      Control Group of Thailand.

PMID- 7561592
TI  - Guidelines for implementation of universal precautions. The Hospital Infection
      Control Group of Thailand.

PMID- 7561594
TI  - Symposium: the administration of hospital environment.

PMID- 7561595
TI  - Symposium: management of infectious waste.

PMID- 7561597
TI  - The 6th, 7th, and 8th Workshops on Nosocomial Infection Control. 1992, 1993,
      1994.

PMID- 7561596
TI  - Tuberculosis revitalized.

PMID- 7561598
TI  - The Second Thai National Prevalence Study on Nosocomial Infections 1992.
AB  - A prevalence study on N.I. in Thailand was repeated in 1992 to evaluate the
      efficacy of the ongoing control programme. The survey included 10,373 patients in
      33 hospitals throughout Thailand. The prevalence rate of N.I. in this study was
      7.3 per cent. When compared with a previous study done in 1988, it was found that
      the prevalence rate had decreased by 4.4 per cent. The reduction of N.I. occurred
      in all types of hospitals, and in all services. Major reduction was found in the
      age groups 5-14, 15-24 and 25-34 years, in orthopaedics, paediatrics and surgical
      departments. Lower respiratory tract infections were the commonest infection in
      this study while urinary tract infection was the commonest in 1988. Overuse of
      antimicrobials was discovered in this survey. The success in reduction of N.I.
      was attributed to the increase in N.I. activities. Campaigns against N.I. since
      1988 seem effective and should be intensified.

PMID- 7561600
TI  - Surgical wound infections in gynaecology at Rajvithi Hospital 1989-1990.
AB  - A survey on surgical wound infections in gynaecological patients at Rajvithi
      Hospital was done. One thousand three hundred and eighty-three cases who were
      operated on from 1989 to 1990 were included. The overall rate of surgical wound
      infection was 4.92%. Vaginal stump infection accounted for 52.9%, and abdominal
      wound infections 30.9%. Aerobic gram negative bacilli were the main group of
      isolated bacteria (45.12%) followed by aerobic gram positive cocci (19.51%).
      Methicillin resistant Staphylococcus aureus (MRSA) were found in 3.66% of the
      isolates. Antimicrobials were used in combination. Two antimicrobials were
      precribed in 4.84%, 3 drugs in 17.74%, 4 drugs in 25.81% and more than 4 drugs in
      drugs in as many as 51.61% of the patients.

PMID- 7561599
TI  - A national study on surgical wound infections 1992.
AB  - A study on SWI was done in 33 hospitals in Thailand between March 16 and May 15,
      1992 involving 15,319 surgical wounds. The average incidence rate of SWI as 2.7
      per cent. It was highest in provincial hospitals. Patients aged under 10 years
      and 51-60 years had higher rates of SWI. It was most prevalent in the surgical
      department followed in rank by accident and orthopaedic departments respectively.
      Wound types were the most important denominator of SWI; the incidence of SWI in
      dirty, contaminated, clean-contaminated and clean wounds were 9.7, 5.1, 1.5 and
      1.3 per cent respectively. Antimicrobial prophylaxis were used in 76.7 per cent
      of the wounds. Ampicillin, gentamicin and cloxacillin were the commonly used
      drugs. Prevention of SWI needs to be improved in provincial hospitals and in the
      use of prophylactic antimicrobials.

PMID- 7561601
TI  - Contamination of blood cultures by switch-needle and nonswitch-needle techniques
      in a paediatric ward.
AB  - To compare the contamination rates of blood culture between the conventional
      switching to a sterile needle before inoculation of blood culture bottles and the
      nonswitch-needle technique, we conducted a prospective crossover study in a
      pediatric infectious disease ward at Lampang Hospital, Thailand from November
      1991 to December 1992. The total number of blood cultures was 764 in which 358
      were in the switch-needle group and 406 in the nonswitch-needle group. The rates
      of contamination were almost identical among the two groups (6.15% v.s. 6.16%).
      It is concluded that careful skin preparation and good handwashing practices of
      the phlebotomists and assistant are more important factors than switching needles
      in reducing contamination during collection of blood for culture. Switching
      needle technique should be discontinued to reduce the risk of needlestick injury
      and the cost of blood culture.

PMID- 7561602
TI  - Infusion-related phlebitis.
AB  - The incidence rate and risk factors of infusion-related phlebitis was studied in
      1993. Thirty-five hospitals were enrolled. Data were collected from 6,256
      infusion sites. Male and female patients were almost equal. Forearms were the
      commonest site of infusion, followed by hand and arm respectively. In 34.1 per
      cent the infusion was interrupted by complications of which 6.2 per cent was
      phlebitis. It was mild in most cases. Increased incidence rates of infusion
      related phlebitis were associated with: the use of plastic cannulas, dextrose
      containing solutions, administration at the sites other than hand and concomitant
      administration of antimicrobials. The incidence rate of phlebitis rose sharply
      after 24 hours of infusion. It is concluded that in addition to proper insertion
      and good nursing care, the avoidance of the above risk factors will lead to a
      lower incidence of infusion-associated phlebitis.

PMID- 7561603
TI  - Infusion phlebitis in medical and surgical patients in Siriraj Hospital.
AB  - A study on infusion phlebitis was done in medical and surgical departments in
      Siriraj Hospitals from February to April 1992. Two hundred and eighty-one
      patients and 406 infusion sites were included. The infusion time was 40.6 +/-
      31.9 hours. The incidence rate of phlebitis was 25.9%. There was no difference in
      its occurrence in medical and surgical patients. Dorsum of the hand was the site
      associated with low incidence and less severe phlebitis. The contrary applied to
      the forearm and arm. Plastic cannulae were associated with higher incidence, more
      severe phlebitis than steel needles, but this was not statistically significant.
      Intravenous antimicrobials were followed by higher incidence and more severe
      phlebitis. The value of early diagnosis of infusion phlebitis so as to halt its
      progress was also demonstrated in the study. In no case was the phlebitis, in the
      most severe form i.e. grade 5, encountered.

PMID- 7561604
TI  - An outbreak of post-operative endophthalmitis in Lampang Hospital.
AB  - An outbreak of post-operative endophthalmitis involving 48 patients from October
      1991 to October 1992 in Lampang Hospital was reported. There were 3 waves of
      clustered cases, i.e. from October 1991 to January 1992, April-June 1992, and
      August-October 1992. Investigation revealed several risk factors: defects in
      sterilization of surgical instruments, poor operating room hygiene, contaminated
      tap water and the use of multiple-dose fluids and medication. Bacteria isolated
      from vitreous fluid showed different bacteria, indicating multiple sources of
      infection or failure of asepsis. Each episode of infection was brought under
      control by removing the risk factors and emphasis on aseptic techniques. The
      value of an effective survey programme for the detection of post-operative
      endophthatmitis was emphasized.

PMID- 7561605
TI  - An outbreak of Norwegian scabies in a surgical ward.
AB  - An outbreak of Norwegian scabies in a surgical ward of a teaching hospital was
      reported. The source of infestation was an elderly diabetic. The epidemic
      involved 28 of 32 medical personnel in the ward and 3 family contacts. All
      infected individuals were given a two-course treatment with hexachlorcyclohexane
      gel. Control of the outbreak was achieved by strict handwashing after patient
      contact, application of gowns and gloves for contact with skin lesions and the
      treatment of infected persons. Norwegian scabies in institutions is on the rise,
      vigilance for its occurrence is needed.

PMID- 7561606
TI  - Type II thyroxine 5'-deiodinase in the rat thymus.
AB  - In the present study we have shown type II thyroxine 5'-deiodination (5'D) in the
      rat thymus. The enzyme activity was identified in crude extract homogenates by
      measuring the 125I released from [3',5'-125I]thyroxine which is used as a
      substrate of the reaction. The release of 125I is dependent on protein tissue
      concentration, time, temperature and pH, and is saturable by increasing the
      substrate concentration, indicating its enzymatic nature. Characteristics of the
      enzyme activity also include a low Km (9.1 nM), its dependence on dithiothreitol,
      and its inhibition by iopanoic acid, but not by propylthiouracil. Experiments to
      investigate the cellular location of the enzyme in the thymic gland showed that
      the enzyme is present in both stromal cells and thymocytes. At the subcellular
      level, 5'D activity was associated with cellular membranes. Thyroid status
      appears to regulate 5'D activity in rat thymus. Hypothyroidism caused an increase
      in thymus 5'D activity. The Km value remained unchanged (9.1 vs 10.5 nM) during
      hypothyroidism, but Vmax increased significantly from 17.7 fmol/mg protein per h
      in euthyroid rats to 53.5 fmol/mg protein per h in hypothyroid rats. 5'D activity
      was also modulated by catecholamines through beta-adrenergic receptors because
      isoproterenol, but not methoxamine or clonidine, could activate the enzyme.
      Because these characteristics define the type II iodothyronine-deiodinating
      pathway in other tissues, we suggest that the rat thymus also shares this
      pathway.

PMID- 7561607
TI  - Pronounced seasonal rhythms in plasma somatolactin levels in rainbow trout.
AB  - The aim of this study was to establish whether there are seasonal or age-related
      changes in circulating levels of somatolactin (SL) in rainbow trout
      (Onchorhynchus mykiss). SL levels were determined in blood sampled at monthly
      intervals over a 2-year period from a population of rainbow trout maintained
      under a natural daylength and temperature regime (North-West England, latitude 54
      degrees 20' N). SL levels displayed a distinct circannual cycle, with peak levels
      in summer (17-20 micrograms/l) and lowest levels occurring in winter (0.2-2
      micrograms/l). This variation in SL levels was closely correlated with water
      temperature (P < 0.001) but was out of phase with changes in daylength. Plasma SL
      levels were significantly higher in both mature male and female fish compared
      with immature fish. Plasma prolactin levels were determined to provide
      information on a hormone structurally related to SL, and also because mammalian
      prolactin is known to show distinct seasonal cycles. However, trout prolactin, in
      contrast to SL, did not show a pronounced seasonal pattern, although prolactin
      levels were significantly, but inversely, correlated with water temperature (P <
      0.001).

PMID- 7561608
TI  - Corticosteroid-binding globulin (CBG) production by hepatic and extra-hepatic
      sites in the ovine fetus; effects of CBG on glucocorticoid negative feedback on
      pituitary cells in vitro.
AB  - Plasma cortisol levels increase in fetal sheep during late gestation and this is
      associated with an increase in plasma corticosteroid-binding globulin (CBG)
      concentrations. However, the relative tissue sources of plasma CBG, the ontogeny
      of its biosynthesis and glycoform composition have not been established in the
      ovine fetus. Therefore we examined whether changes in plasma corticosteroid
      binding capacity (CBC) in fetal sheep during late gestation were associated with
      different patterns of glycosylation and reflected changes in tissue CBG
      expression. Since free cortisol is considered the bioactive fraction, we measured
      changes in the percent and absolute free cortisol in fetal plasma during late
      gestation. In order to examine whether CBG alters cortisol negative feedback at
      the level of the fetal pituitary, we also examined the effect of exogenous CBG in
      mediating the glucocorticoid-induced suppression of basal and corticotrophin
      releasing hormone (CRH)-stimulated ACTH release from fetal pituitary cells in
      culture. The mean free cortisol concentration in plasma was not different between
      days 15 and 20 prior to parturition, and between 5 and 10 days prepartum,
      although it did rise between these times. Plasma CBC in chronically catheterized
      fetuses rose from 23.3 +/- 4.6 ng/ml at day 115 to 86.5 +/- 20.8 ng/ml at term
      and then decreased rapidly after birth. Between day 125 and day 140 of pregnancy
      approximately 10% of fetal plasma CBG was retarded by Concanavalin-A
      chromatography. This proportion increased at birth and attained adult values of >
      70% by one month of age. By Northern blotting the relative levels of CBG mRNA in
      the fetal liver did not change between days 100 and 125, then increased
      significantly at day 140, but declined at term and in newborn lambs. CBG mRNA was
      undetectable in total RNA from lung, kidney, hypothalamus and placentomes, but
      was present in the fetal pituitary at days 125 and 140. Reverse transcription-PCR
      was used to confirm the presence of CBG mRNA in pituitary tissue from term
      fetuses. In cultures of term fetal pituitary cells, added CBG attenuated the
      cortisol- but not the dexamethasone-mediated suppression of basal and CRH
      stimulated ACTH release. We conclude that in fetal sheep there is an increase in
      the corticosteroid binding capacity of plasma during late pregnancy which
      regulates, in part, free cortisol levels in the circulation. The liver is the
      major site of CBG biosynthesis in the fetus and at least until day 140 of
      gestation the rise in plasma CBC is associated with an increase in hepatic CBG
      mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7561609
TI  - Effects of growth hormone antagonists on 3T3-F442A preadipocyte differentiation.
AB  - We have previously shown that a bovine (b) GH antagonist, bGH-M8, which possesses
      three amino acid substitutions in its third alpha-helix, inhibits mouse 3T3-F442A
      preadipocyte differentiation. In the current studies, we used the bGH and human
      (h) GH analogs with single amino acid substitution, bGH-G119R and hGH-G120R, for
      determining their biological activity using the preadipocyte differentiation
      assay. Short-term and long-term GH-inducible events were studied during adipose
      differentiation, including late marker gene expression (adipocyte protein 2),
      immediate early gene induction (c-fos), and tyrosine phosphorylation of
      intracellular proteins. The results demonstrated that these GH analogs not only
      failed to induce these three events, but also antagonized GH induction of c-fos
      expression and phosphorylation of proteins of apparent molecular mass of 95 kDa.
      Our present study agrees with the notion that GH must bind to the GH receptor via
      site one and with a second GH receptor molecule (or with some yet unidentified
      'second target') through GH binding site two. This interaction is important for
      subsequent GH-dependent biological events.

PMID- 7561610
TI  - Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a
      further potential site of growth hormone regulation of IGF-I action.
AB  - We recently identified and characterized a protease present in rat serum which is
      capable of generating des(1-3)IGF-I. In this study, we have investigated the
      effects of GH deficiency and replacement on the activity of this protease in rat
      serum and tissue extracts. Protease activity was significantly higher in sera
      from hypophysectomized (hypox) rats than sham-operated rats (P < 0.001) and GH
      treatment of hypox rats (human GH, 100 micrograms/100 g body weight i.p. for 10
      days) significantly reduced the levels towards normal. The addition of IGF-I to
      hypox rat serum to achieve IGF-I concentrations comparable with or greater than
      that seen in normal rat serum had no effect on the measured protease activity.
      Protease activity was also detected in tissue extracts. The level of protease
      activity in the various tissues from sham-operated rats demonstrated the
      following order: liver > testes > heart > skeletal muscle > lung > thymus >
      kidney > brain > spleen. In all tissue extracts examined, except that from the
      lung, the levels of protease activity were higher in extracts from hypox rats
      compared with sham-operated rats. The largest differences between tissue extracts
      from hypox and sham-operated rats were seen in spleen (4-fold higher), kidney
      (2.27-fold), testes (1.55-fold) and heart (1.31-fold). In the liver, kidney and
      testes, GH treatment significantly reduced protease activity. Since the pattern
      of serum IGF-binding proteins (IGFBPs) differ in hypox rats compared with normal
      rats, we determined whether these changes could result in enhanced serum binding
      of des(1-3)IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561611
TI  - Nitric oxide synthase in the rat fallopian tube is regulated during the oestrous
      cycle.
AB  - Nitric oxide produced from L-arginine by nitric oxide synthase (NOS) acts in a
      variety of biological processes via the stimulation of guanylyl cyclase and
      subsequent elevation of cGMP. Constitutive, calcium-dependent isoforms of NOS are
      found in endothelial cells (eNOS) and neurones (nNOS), while macrophages express
      an inducible, calcium-independent isoform (iNOS) in response to the action of
      certain cytokines or bacterial endotoxin. While the regulation of NOS by
      exogenous glucocorticoids and steroid hormones is well documented, the effects of
      endogenous steroid hormones on NOS activity, such as those released during the
      oestrous cycle, is unknown. Here we demonstrate, using specific antibodies for
      eNOS, nNOS and iNOS, the presence of NOS in the epithelium of rat fallopian tubes
      at pro-oestrus, late pro-oestrus, oestrus, metoestrus and dioestrus. Western blot
      analysis of rat fallopian tube homogenates revealed a protein band at
      approximately 125 kDa which was recognised by antibodies to different isoforms of
      NOS, but no bands at the expected molecular weights (eNOS, 140 kDa; nNOS, 160
      kDa; iNOS, 135 kDa). NOS activity in fallopian tubes was measured by the
      conversion of L-[3H]arginine to L-[3H]citrulline. Both calcium-dependent and 
      independent NOS activities were present. However, in late pro-oestrus when
      circulating oestrogens are low, NOS activity was reduced in comparison to all
      other stages of the oestrous cycle. Thus we show that NOS is present in the
      epithelial lining of the fallopian tube and is recognised at a previously
      undescribed molecular weight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561612
TI  - Testicular serotonin is related to mast cells but not to Leydig cells in the rat.
AB  - Testicular serotonin (5HT) concentrations were determined by HPLC in the testes
      of rats treated neonatally with oestradiol benzoate (EB) and in adult rats
      treated with the Leydig cell cytotoxic ethylene dimethane sulphonate (EDS). 5HT
      concentrations were related to mast cell numbers. EB-treated rats showed an
      accumulation of mast cells in the testes at 35 and 70 days of age and increased
      5HT concentrations in both the interstitial fluid and the testicular capsule,
      whereas no increases in 5HT concentrations or in the number of mast cells were
      found for the ventral prostate of these animals. On the contrary, 5HT
      concentrations were not related to the number of Leydig cells. In EB-treated
      rats, in which Leydig cells were nearly absent at 35 days of age, 5HT
      concentrations were significantly increased. Furthermore, EDS-treated rats did
      not show significant changes in 5HT concentrations, in spite of the elimination
      of Leydig cells. These data suggest that mast cells are a major source of
      serotonin in the rat testis.

PMID- 7561613
TI  - Differential acetylation of pro-opiomelanocortin-derived peptides in the
      pituitary gland of Xenopus laevis in relation to background adaptation.
AB  - Immunocytochemical analysis revealed the presence of acetylated endorphins in
      both melanotropes and corticotropes of the pituitary gland of Xenopus laevis.
      Chemical acetylation studies to determine the steady-state level of acetylated
      versus non-acetylated endorphins showed that virtually all endorphins are
      acetylated in both melanotropes and corticotropes. Apparently Xenopus is unique
      among vertebrates as non-acetylated endorphins are major end-products in the
      distal lobe of all other vertebrate species studied thus far. The dynamics of
      endorphin biosynthesis in melanotrope cells using pulse-chase analysis coupled to
      immunoaffinity chromatography revealed that processing of pro-opiomelanocortin to
      produce N-terminal-acetylated endorphins is very rapid. To determine the effect
      of long-term background adaptation on acetylation status of endorphins and alpha
      MSH-related peptides, Xenopus laevis were adapted for 3 or 6 weeks to either a
      black or a white background. In both physiological states the major intracellular
      form of alpha-MSH-related peptides in melanotropes was desacetyl alpha-MSH while
      the major endorphin-related peptide was alpha, N-acetyl-beta-endorphin[1-8]. In
      the medium of superfused neuro-intermediate lobes of black background-adapted
      animals the major form of secreted melanotropins and endorphins was alpha-MSH and
      alpha, N-acetyl-beta-endorphin[1-8] respectively. We conclude that there is a
      marked spatio-temporal difference in acetylation of melanotropin and endorphins,
      with rapid intracellular acetylation of endorphins while melanotropin is
      acetylated at the time of its exocytosis. In the medium of superfused
      neurointermediate lobes of white background-adapted animals the amount of
      desacetyl alpha-MSH was much higher than in the medium of lobes of black-adapted
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561614
TI  - Follicular dynamics and secretion of inhibin and oestradiol-17 beta during the
      oestrous cycle of the hamster.
AB  - Plasma and ovarian levels of inhibin were determined by a radioimmunoassay (RIA)
      at 3-h intervals throughout the 4-day oestrous cycle of hamsters. Plasma
      concentrations of FSH, LH, progesterone, testosterone and oestradiol-17 beta were
      also determined by RIAs. In addition, hamsters were injected at various times
      with human chorionic gonadotrophin (hCG) to determine the follicular development.
      The changes in plasma concentrations of FSH after injection of antisera to
      oestradiol-17 beta (oestradiol-AS) and inhibin (inhibin-AS) on the morning of day
      2 (day 1 = day of ovulation) were also determined. Plasma concentrations of
      inhibin showed a marked increase on the afternoon of day 1, remained at plateau
      levels until the morning of day 4, then increased abruptly on the afternoon of
      day 4 when preovulatory LH and FSH surges were initiated. A marked decrease in
      plasma concentrations of inhibin occurred during the process of ovulation after
      the preovulatory gonadotrophin surges. An inverse relationship between plasma
      levels of FSH and inhibin was observed when the secondary surge of FSH was in
      progress during the periovulatory period. Plasma concentrations of oestradiol-17
      beta showed three increase phases and these changes differed from those of
      inhibin. Changes in plasma concentrations of oestradiol-17 beta correlated well
      with the maturation and regression of large antral follicles. Follicles capable
      of ovulating following hCG administration were first noted at 2300 h on day 1.
      The number of follicles capable of ovulating reached a maximum on the morning of
      day 3 (24.8 +/- 0.6), and decreased by 0500 h on day 4 (15.0 +/- 1.1),
      corresponding to the number of normal spontaneous ovulations.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7561615
TI  - Changes in plasma beta-cell tropin concentrations during pregnancy in rats.
AB  - The mechanisms which initiate and maintain the energy partitioning into maternal
      tissues during pregnancy are unknown. The present study shows that in each of the
      weeks prior to pregnancy in the rat, plasma beta-cell tropin (beta CT)
      concentrations (nmol/l) were 0.68 +/- 0.10, 0.61 +/- 0.14 and 0.73 +/- 0.11 (n =
      11, mean +/- S.E.M.). During early (1-3 days) pregnancy the concentration rose to
      1.32 +/- 0.26 and by early-mid (7-10 days) pregnancy they had increased to 1.96
      +/- 0.41. By mid-late (14-17 days) pregnancy plasma beta CT concentration had
      declined to the prepregnancy concentrations (0.67 +/- 0.16). This mid-term
      increase in the circulating concentration of the lipogenic hormone beta CT may
      contribute to the deposition of lipid associated with the early period of
      gestation. The increased circulating beta CT could be derived from the pituitary
      gland neurointermediate lobe or by secretion from the placenta. It should be
      emphasised that the measurements in the present study represent a 'snap-shot' at
      discrete intervals and do not provide information about the dynamic hormonal
      interplay which occurs physiologically.

PMID- 7561616
TI  - Glucagon-like peptide-1 binding to rat hepatic membranes.
AB  - We have found [125I]glucagon-like peptide (GLP)-1(7-36)amide specific binding
      activity in rat liver and isolated hepatocyte plasma membranes, with an M(r) of
      approximately 63,000, estimated by cross-linking and SDS-PAGE. The specific
      binding was time- and membrane protein concentration-dependent, and equally
      displaced by unlabelled GLP-1(7-36)amide and by GLP-1(1-36)amide, achieving its
      ID50 at 3 x 10(-9) M of the peptides. GLP-1(7-36)amide did not modify the basal
      or the glucagon (10(-8) M)-stimulated adenylate cyclase in the hepatocyte plasma
      membranes. These data, together with our previous findings of a potent glycogenic
      effect of GLP-1(7-36)amide in isolated rat hepatocytes, led us to postulate that
      the insulin-like effects of this peptide on glucose liver metabolism could be
      mediated by a type of receptor probably different from that described for GLP-1
      in pancreatic B-cells or, alternatively, by the same receptor which, in this
      tissue as well as in muscle, uses a different transduction system.

PMID- 7561618
TI  - Fertilization-promoting peptide: a novel peptide, structurally similar to TRH,
      with potent physiological activity.

PMID- 7561617
TI  - Effect of restriction of placental growth on expression of IGFs in fetal sheep:
      relationship to fetal growth, circulating IGFs and binding proteins.
AB  - To determine whether tissue production of the IGFs is altered when fetal growth
      is retarded, IGF-I and -II mRNAs were measured in tissues of fetal sheep
      subjected to placental restriction and the relationships between IGF gene
      expression, circulating IGF protein and fetal growth were examined. The majority
      of potential placental attachment sites were surgically removed from the uterus
      of 12 non-pregnant ewes to restrict placental size in a subsequent pregnancy.
      Blood and tissues were collected at 121 days of gestation (term = 150) in 12
      fetuses with restricted placental size and eight normal fetuses. IGF-I and IGF-II
      mRNA was detected by solution hybridization/ribonuclease protection assay in
      placenta and all fetal tissues studied. IGF-I mRNA was most abundant in skeletal
      muscle and liver and IGF-II mRNA was highest in kidney and lung. Restriction of
      placental size reduced fetal weight by 17% and reduced the pO2 (18%) and glucose
      concentration (23%) of fetal blood. Placental restriction also reduced IGF-I mRNA
      in fetal muscle (P < 0.002), lung (P < 0.05) and kidney (P < 0.01) but had no
      significant effect on IGF-II mRNA in any tissue. IGF-I mRNA in fetal liver,
      kidney and skeletal muscle correlated positively with the concentration of IGF-I
      protein in fetal blood (P < 0.01). There was no relationship between the
      concentration of IGF-II protein in fetal blood and IGF-II mRNA in any fetal
      tissue examined. The concentration of IGF-binding protein-3 (IGFBP-3) in fetal
      arterial blood plasma measured by RIA correlated positively with fetal weight and
      with plasma IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561619
TI  - Insulin and IGF-I binding and tyrosine kinase activity in fish heart.
AB  - A study is presented of the binding of insulin and IGF-I to their respective
      receptors in the heart muscle of carp (Cyprinus carpio), coho salmon
      (Oncorhynchus kisutch), brown trout (Salmo trutta fario) and Sprague-Dawley rats.
      Receptor preparations were partially purified by wheat germ agglutinin affinity
      chromatography. Specific binding of insulin/100 mg cardiac muscle was much lower
      in fish (from 5.6 to 9.2%) than in rat (52.0 +/- 5.0%). In both carp and trout,
      insulin binding to the cardiac muscle receptor preparation was significantly
      higher than in the white skeletal muscle (3.4 +/- 0.3%, carp and 0.9 +/- 0.3%,
      trout) or in the red skeletal muscle of carp (5.5 +/- 0.8%). Specific binding of
      IGF-I/100 mg fish heart preparation ranged between 44 and 68%, surpassing IGF-I
      binding in the rat heart (20 +/- 6%). The affinity of IGF-I receptors in fish
      heart (Kd 0.17-0.19 nM) was higher than that in rat heart (Kd 0.40 +/- 0.05 nM)
      or insulin receptors in fish and rat heart preparations (0.25-0.72 nM). The IGF-I
      receptor binding was highly specific and required at least 100 nM insulin to
      cause any displacement of the bound ligand. Receptor tyrosine kinase activity
      could be stimulated in a dose-dependent manner by insulin and IGF-I, although in
      equimolar doses IGF-I was more potent than insulin. Maximum stimulation of
      tyrosine kinase activity (210-230%) in fish heart was in the same range as in
      other piscine tissues (150-260%) or in rat cardiac muscle (200-250%).

PMID- 7561620
TI  - Corticotrophin-releasing hormone (CRH)-binding protein interference with CRH
      antibody binding: implications for direct CRH immunoassay.
AB  - Direct immunoassay of plasma corticotrophin-releasing hormone (CRH) is
      potentially subject to interference from high levels of CRH-binding protein (CRH
      BP) that exist in the human circulation. In this study, we tested the effect of
      CRH-free, native CRH-BP (6.4 nmol/l) purified from human plasma, CRH-BP diluent
      alone, normal human plasma (containing 5.8 nmol endogenous CRH-BP/l) and normal
      sheep plasma (containing no CRH-BP) on the binding of 125I-labelled CRH tracer to
      five N-terminal and four C-terminal CRH antibodies. All anti-(1-20)CRH N-terminal
      antibody dilution curves displayed marked inhibition of binding in the presence
      of purified CRH-BP and human plasma in comparison with the curves with the
      control diluent or sheep plasma. Almost no inhibition of binding was obtained
      with any of the C-terminal antibodies (all directed against epitopes within the
      last six amino acids of CRH) and the four dilution curves were nearly
      superimposable. Liquid-phase CRH IRMAs were then developed with different
      combinations of two of each of the N- and C-terminal antibodies, using
      radiolabelled IgG prepared from purified C-terminal antisera as tracer and raw N
      terminal antisera as the link antibodies to the separating system. The addition
      of dilutions of purified CRH-BP over the range 1.25-20 nmol/l to the IRMA
      standard curve in assay buffer resulted in a dose-dependent reduction in the
      signal; with 5 nmol CRH-BP/l, a level commonly found in human plasma, the
      reduction in binding was 67% and 81% in two different IRMAs at a CRH
      concentration of 631 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561622
TI  - Acute hyperinsulinemia, androgen homeostasis and insulin sensitivity in healthy
      man.
AB  - The acute effects of hyperinsulinemia on androgen homeostasis and a possible
      association of androgens to insulin sensitivity, serum lipids and lipoproteins
      and to lipid oxidation were examined in 19 healthy males (27 +/- 1 yrs, body mass
      index 24 +/- 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic
      clamp was performed and glucose and lipid oxidation were determined by indirect
      calorimetry. During hyperinsulinemia serum sex hormone-binding globulin (SHBG)
      concentration decreased by 5% (P < 0.01), insulin-like growth factor binding
      protein (IGFBP-1) by 88% (P < 0.001) and dehydroepiandrosterone sulphate (DHEAS)
      by 12% (P < 0.001), with no change in total or free testosterone concentrations.
      In the basal state, IGFBP-1 and C-peptide were inversely related (r = -0.54, P <
      0.05). Fasting concentrations of serum free testosterone (r = 0.59, P < 0.01) and
      DHEAS (r = 0.47, P < 0.05) correlated positively with serum free fatty acid (FFA)
      concentrations during hyperinsulinemia, but not with fasting FFA level. Lipid
      oxidation rate in the basal state correlated positively to the decline in SHBG (r
      = 0.61, P < 0.01) and DHEAS concentrations (r = 0.62, P < 0.01) during
      hyperinsulinemia. While the fasting serum high density lipoprotein cholesterol
      level correlated positively with the insulin-induced decline in DHEAS level (r =
      0.58, P < 0.01), no associations were found between serum androgens and total
      cholesterol, low density lipoprotein cholesterol or triglyceride concentrations.
      Insulin sensitivity was not related to SHBG, IGFBP-1, DHEAS or testosterone
      concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561621
TI  - Growth hormone and longitudinal bone growth in vivo: short-term effect of a
      growth hormone antiserum.
AB  - The control of longitudinal growth is poorly understood but GH is considered to
      be one of the major hormones regulating postnatal growth. However, there is
      dispute as to whether it has a direct or indirect action. To study the role of GH
      we used a polyclonal antiserum to rat GH and investigated changes in cell
      proliferation and enzyme activities associated with bone formation and resorption
      during longitudinal growth. IGF-I levels were measured by two independent RIAs,
      DNA synthesis by bromodeoxyuridine incorporation followed by immunocytochemistry
      and enzyme activities were quantified in situ by microdensitometry. After 1 day
      the percentage of chondrocytes undergoing DNA synthesis within the proliferative
      zone was reduced but no other parameters were affected. By day 4 the labelling
      index was the same as in pair-fed animals but the number of chondrocytes
      synthesising DNA was reduced as was the total width of the growth plate and that
      of the proliferative zone. Alkaline phosphatase (associated with mineralisation)
      was unchanged but glucose 6-phosphate dehydrogenase activity (associated with
      cell proliferation) was decreased. Osteoclastic tartrate-resistant acid
      phosphatase activity (associated with bone resorption) was also significantly
      reduced. Similar changes were apparent after 10 days. At no time was the
      circulating level of IGF-I decreased. These data suggest that, during
      longitudinal growth, GH affects the number of proliferating chondrocytes but not
      the percentage of cells undergoing DNA synthesis, indicating that its primary
      role may be on the commitment of prechondrocytes to a proliferative state.
      Furthermore, while GH does not seem to have any effect on skeletal mineralisation
      it may stimulate osteoclastic resorption of the primary spongiosa.

PMID- 7561623
TI  - Migratory fat deposition in European quail: a role for prolactin?
AB  - The present study addresses the role of prolactin as a regulator of migratory
      fattening in European quail (Coturnix coturnix). Plasma prolactin levels in
      captive birds undergoing migratory fattening in an outdoor aviary and in the
      laboratory were measured by radioimmunoassay with an antibody raised against
      recombinant-derived chicken prolactin. No strong association between prolactin
      and migratory fattening was apparent, and prolactin levels were more closely
      related to daylength, with the highest concentrations being reached on long days.
      Plasma prolactin profiles were similar in intact and castrated male quail.
      Prolactin was secreted in a daily rhythm, with the highest concentrations
      occurring early in the photophase. However, when birds were food-restricted for
      50 days during a migratory phase, there was no difference in fat deposition
      between birds food-deprived for the first half of the daily photophase compared
      with those deprived for the second half. Fattening was reduced in the food
      restricted birds relative to ad libitum-fed controls, but there was no difference
      in plasma prolactin levels between the groups. Injections of ovine prolactin (4
      mg/kg) significantly increased food intake and body mass of birds maintained on
      long days, but there were no differences in fattening between birds injected in
      the morning compared with those injected in the afternoon. Collectively, these
      results do not support a major role for prolactin in the regulation of migratory
      fat deposition in European quail.

PMID- 7561624
TI  - Effect of ovarian steroid hormones and the presence of the fetus on oxytocin gene
      expression in the uterus.
AB  - Oxytocin (OT) is a neurohypophysial hormone with potent stimulating activity of
      the pregnant uterus, but its physiological role in parturition is still unclear.
      Recently, OT was found to be synthesized in the pregnant uterus, indicating that
      OT originating from the uterus, not from the posterior pituitary gland, may
      trigger the onset of labour. In order to define the factors responsible for the
      induction of uterine OT, the effect of ovarian steroid hormones and conceptus on
      the induction of OT mRNA in the rat uterus was examined by Northern and dot blot
      hybridization analysis. OT mRNA in the uterus started to increase on day 14 of
      pregnancy and showed very high levels at the time of parturition. Uterine OT mRNA
      was not altered by any steroid treatment, oestradiol-17 beta (0.2 microgram),
      progesterone (4 mg) or both in combination, for 6 days. The gravid horn of the
      uterus had 3.6-fold as much OT mRNA as the non-gravid horn on day 21 of pregnancy
      in hemipregnant rats with one ligated oviduct. The ovarian steroid hormones could
      not induce accumulation of OT mRNA in the uterus of ovariectomized rats, at least
      under the conditions used, but the presence of a conceptus may be critical for
      the very high levels of OT mRNA.

PMID- 7561625
TI  - Effect of hypothyroidism on the pituitary-gonadal axis in the adult female rat.
AB  - The pituitary-ovarian axis was studied after withdrawal of thyroid hormone in
      131I-radiothyroidectomized adult female rats. Oestrous cycles became prolonged
      and irregular within 2 weeks after the supply of thyroid hormone was stopped. If
      an LH surge occurred in hypothyroid rats on the day of vaginal pro-oestrus it was
      significantly greater in rats which had been made hypothyroid for 4-5 weeks than
      in controls; in hypothyroid rats with an LH surge on pro-oestrus, plasma
      progesterone showed a rise similar to that in controls at pro-oestrus; the
      ovulation rate was decreased in hypothyroid rats. About half of the rats from
      which blood was sampled daily in the afternoon between 7 and 18 days after tri
      iodothyronine (T3) withdrawal had 1 day of pro-oestrus; on this day the LH surge
      was higher than in controls. On days 2 and 1 before and days 1 and 2 after this
      pro-oestrus, plasma progesterone was similar to that of controls on days 2 and 1
      before and days 1 and 2 after pro-oestrus respectively. However, progesterone was
      higher in the period before and after these days. The other hypothyroid rats
      showed no pro-oestrus and no LH surge during this period, while their plasma
      progesterone levels were high on all days. On the morning of day 10 after T3
      withdrawal and 5 days after the preceding pro-oestrus, most hypothyroid rats had
      high progesterone and low oestradiol plasma levels.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7561626
TI  - Nuclear translocation of neuropeptides: possible nuclear roles.

PMID- 7561627
TI  - Suppression of LH secretion in food-restricted lactating females: effects of
      ovariectomy and bromocryptine treatment.
AB  - It has been shown that restricting food in lactating rats for the first 2 weeks
      postpartum at a level of 60% of the ad-libitum daily ration increases the length
      of lactational dioestrus by about 7 days but little is known about correlated
      changes in hormone levels. In the first experiment we report changes in LH,
      prolactin (PRL) and ACTH secretion in food-restricted and ad-libitum fed
      lactating rats at various stages of lactation. Our results demonstrate that food
      restriction during the first 2 weeks of lactation did not affect PRL or ACTH
      secretion, but decreased plasma LH levels despite comparable GnRH receptor
      density between food-restricted and ad-libitum fed females. In the second
      experiments we investigated a possible causal relationship between the increased
      secretion of progesterone seen in food-restricted females and the suppression of
      plasma LH levels, by determining the effects of bromocryptine treatment and
      ovariectomy on LH secretion in both ad-libitum fed and food-restricted lactating
      females. LH suppression in food-restricted lactating females was not affected by
      ovariectomy or bromocryptine treatment, although the latter treatment
      significantly increased GnRH receptor number. These data suggest that factors
      other than ovarian steroids, PRL or increased adrenocortical activity modulate LH
      secretion and the length of lactational dioestrus in food-restricted lactating
      females.

PMID- 7561628
TI  - Structural remodelling of reproductive tissues.

PMID- 7561629
TI  - 17 beta-hydroxysteroid dehydrogenase: isozymes and mutations.

PMID- 7561630
TI  - Retinoids: transport, metabolism, and mechanisms of action.
AB  - The retinoids comprise a family of polyisoprenoid lipids that includes vitamin A
      (retinol) and structurally related compounds. The biological activity of
      retinoids can be modified, for example, by changes in the molecules' state of
      oxidation and cis/trans isomerization. Their activity is also dependent on the
      levels of specific types of retinoid-binding proteins which exist in
      extracellular, cytosolic and nuclear compartments. The role of retinoids in gene
      expression represents an important biological function for this family of
      molecules. Retinoid-dependent modulation of gene expression is critical for
      normal cell and tissue function in mature as well as developing animals. Despite
      significant advances in the understanding of retinoid biological activity,
      important questions remain concerning aspects of retinoid metabolism, cellular
      uptake, intracellular trafficking and regulation of gene transcription. The
      purpose of this review is to present these topics as a compendium of retinoid
      endocrinology.

PMID- 7561631
TI  - Effects of sodium depletion on the response of rat adrenal zona glomerulosa cells
      to stimulation by neuropeptides: actions of vasoactive intestinal peptide,
      enkephalin, substance P, neuropeptide Y and corticotrophin-releasing hormone.
AB  - There are several neuropeptides, present in nerves supplying the rat adrenal zona
      glomerulosa, which have been shown to stimulate aldosterone secretion in the
      intact perfused rat adrenal preparation. The purpose of the present study was
      twofold: first, to determine whether these peptides acted directly on
      adrenocortical cells by examining their effects on collagenase-dispersed rat zona
      glomerulosa cells, and second, to investigate the likely physiological
      significance of these actions, by determining whether the responses of zona
      glomerulosa cells to neuropeptides were changed by prior sodium depletion. Of the
      peptides tested, neuropeptide Y (NPY) and substance P had only a minor effect on
      aldosterone secretion, which was not substantially affected by sodium depletion.
      Corticotrophin-releasing hormone (CRH) had a significant stimulatory effect on
      aldosterone secretion, but neither the threshold concentration for significant
      stimulation nor the maximal response to stimulation were altered by prior sodium
      depletion. Vasoactive intestinal peptide (VIP), on the other hand, had little
      effect on aldosterone secretion by cells from normal animals, but was a potent
      stimulus to aldosterone secretion in cells obtained from sodium-depleted animals.
      The response to the Met-enkephalin analogue, [D-Ala2-Met2]-enkephalinamide
      (DALA), was also significantly enhanced by prior sodium depletion. Experiments
      using the angiotensin II receptor blocker, saralasin, were carried out to
      determine whether the enhanced actions of DALA and VIP seen in sodium depletion
      may be a result of activation of angiotensin II receptors, known to be increased
      in sodium depletion. Saralasin did not affect the response to either peptide.
      These data suggest that all the peptides tested may be able to stimulate
      aldosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561632
TI  - Degradation of IGF-I in the adult rat gastrointestinal tract is limited by a
      specific antiserum or the dietary protein casein.
AB  - To investigate the potential of IGF-I peptides as therapeutics in the gut, the
      survival profiles of a bolus of 125I-labelled IGF-I (8.6 ng) in vivo in various
      ligated gut segments of fasted adult rats have been examined. The intactness of
      IGF-I tracer in the flushed luminal contents was estimated by trichloroacetic
      acid precipitation, antibody and receptor binding assays. It was found that IGF-I
      was degraded very rapidly in duodenum and ileum segments with a half-life (t1/2)
      of 2 min by all three methods. IGF-I was slightly more stable in the stomach
      (t1/2 = 8, 5 and 2.5 min by the above three methods), and considerably more
      stable in the colon (t1/2 = 38, 33 and 16 min as judged by the three methods).
      Rates of degradation in gut flushings in vitro were similar to the in vivo rates
      except for the colon, where IGF-I was proteolysed more rapidly in vivo. As a
      means of developing gut-stable and active forms of IGF-I, several approaches were
      examined for their effectiveness in prolonging IGF-I survival in the upper gut.
      It was found that the extension peptide on the analogue, LR3IGF-I did not protect
      IGF-I, nor did association with IGF-binding protein-3. However, an IGF-I
      antiserum was effective in prolonging IGF-I half-life in duodenum fluid by 28
      fold. Charge interaction between IGF-I and heparin could also protect IGF-I in
      the stomach but not in duodenum flushings. Furthermore, casein (a non-specific
      dietary protein) and to a lesser extent, BSA and lactoferrin, were effective in
      preserving IGF-I structural integrity and receptor binding activity in both
      stomach and duodenum fluids. It can be concluded that IGF-I cannot be expected to
      retain bioactivity if delivered orally because of rapid proteolysis in the upper
      gut, but the use of IGF antibodies and casein could represent useful approaches
      for IGF-I protection in oral formulae.

PMID- 7561633
TI  - Comparison of the effects of growth hormone-releasing hormone and hexarelin, a
      novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in
      humans with or without glucocorticoid excess.
AB  - The aim of our study was to investigate the effect of hexarelin, a novel GH
      releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alone or in
      combination) on GH secretion in adult patients with increased somatostatin tone
      due to chronic glucocorticoid excess. We studied seven adult patients undergoing
      long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for
      non-endocrine diseases (six females and one male, age range 42-68 years) and one
      subject (female, age 31 years) with endogenous hypercortisolism due to adrenal
      adenoma. Six normal subjects (four females and two males) matched for sex and age
      with the patients and not undergoing any therapy served as controls. All the
      subjects underwent the following three tests in random order: (1) human GHRH (1
      29)NH2 (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min, (2)
      hexarelin (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min and
      (3) hexarelin (100 micrograms in 1 ml of saline) plus GHRH (100 micrograms in 1
      ml saline) injected as an i.v. bolus at 0 min. After GHRH alone the patients with
      glucocorticoid excess showed a blunted GH response as compared with normal
      subjects (median delta GH: 0.9, range 0-5.6 micrograms/l vs 7:1, range 0.3-14.9
      micrograms/l). No significant differences were observed in the steroid-treated
      group with respect to normal subjects after hexarelin alone (median delta GH:
      15.5, range 1.9-45.2 micrograms/l vs 17.9, range 5.5-53.9 micrograms/l).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7561634
TI  - Uptake of thyroxine in the human choriocarcinoma cell line JAR.
AB  - We have studied the uptake of 125I-thyroxine (125I-T4) in the human
      choriocarcinoma cell line JAR. Uptake of 125I-T4 was time-dependent,
      stereospecific and reversible, with a saturable component of 33% after 120 min of
      incubation. Kinetic analysis of the initial specific uptake rates indicated the
      presence of a single uptake process with a Michaelis constant of 59.4 +/- 13.9 nM
      (n = 12) and maximum velocity of 0.29 +/- 0.06 pmol/min per mg protein. Uptake
      was dependent on intracellular energy as, in the presence of 2 nM potassium
      cyanide, saturable uptake was reduced to 60.6 +/- 8.5% (n = 4) of control uptake.
      Uptake was also temperature-dependent. Saturable 125I-T4 uptake after 60 min of
      incubation was 26.1 +/- 3.0% at 25 degrees C (n = 6) and 27.3 +/- 5.7% at 4
      degrees C of control uptake at 37 degrees C. Ouabain did not inhibit 125I-T4
      uptake indicating that the uptake was independent of the Na+ gradient across the
      cell membrane. Although T4 uptake was stereospecific, as D-T4 failed to inhibit
      125I-L-T4 uptake, it was not specific for T4, as tri-iodothyronine (T3) and
      reverse T3 also inhibited 125I-T4 uptake. We conclude that JAR cells have a
      saturable, stereospecific and reversible membrane transport mechanism for T4
      which is dependent on intracellular energy, but independent of the Na+ gradient
      across the cell membrane.

PMID- 7561636
TI  - Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but
      reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea
      pig.
AB  - We have tested whether an animal with substantial amounts of both IGF-I and IGF
      II in circulation, such as the guinea pig, would respond to chronic IGF infusion
      in the same manner as the adult rat, which has negligible amounts of IGF-II in
      blood. Female guinea pigs of 350 g body weight were continuously infused for 7
      days with recombinant guinea pig IGF-I or -II (120 or 360 micrograms/day) or long
      R3 IGF-I (LR3IGF-I) (120 micrograms/day), an analogue which has much reduced
      affinities for IGF binding proteins. IGF-I or IGF-II infusion led to substantial
      increases in plasma IGF-I or IGF-II respectively in comparison with vehicle
      infused animals. Nevertheless, body weight gain, feed intake, feed conversion
      efficiency and carcass composition were not significantly affected by any
      treatment (significance was deemed to be P < 0.05). Amongst the tissues examined
      only the fractional weight (g/kg body weight) of the adrenals was increased, and
      that only by the higher dose (360 micrograms/day) of IGF-I. However, the
      fractional weight of adrenals, gut, kidneys and spleen were significantly
      increased by LR3IGF-I, but again overall growth was not stimulated. A possible
      explanation for the lack of IGF-I effects is that total circulating IGF
      concentrations were not increased by these treatments. IGF-II significantly
      raised total IGF concentrations at the higher dose only. Plasma IGF-I was reduced
      by IGF-II infusion, as was plasma IGF-II by IGF-I infusion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7561635
TI  - Hormonal control of insulin-like growth factor-I and growth hormone receptor mRNA
      expression by porcine hepatocytes in culture.
AB  - The effects of various hormones commonly added to hepatocyte culture media upon
      the expression of the GH receptor (GHR) and insulin-like growth factor-I (IGF-I)
      genes in cultured porcine hepatocytes were investigated. Preliminary
      investigations indicated that there was an absolute requirement only for insulin,
      with high losses of cell viability upon long term exclusion of insulin from the
      culture medium. The decline in GHR expression with time in culture was found to
      be less when high levels of glucose were included in the medium. Therefore the
      basal culture medium used in these studies was Williams' medium E supplemented
      with 0.2% (w/v) BSA, 5000 mg glucose/l and 100 nmol porcine insulin/l. The
      addition of dexamethasone (10 nmol/l) increased the expression of both GHR and
      IGF-I (class 1 transcripts only) mRNA (p < 0.001 and P < 0.05 respectively), and
      resulted in an increased responsiveness of IGF-I mRNA expression to GH (1
      microgram/ml), when the two were added in combination (although only class 1
      transcripts were shown to be statistically significant, P < 0.01). The addition
      of either thyroid hormone (1 nmol/l T3 or T4) alone also increased the expression
      of GHR mRNA (P < 0.01) in addition to the dexamethasone stimulated expression,
      with T4 appearing to decrease IGF-I expression slightly (P < 0.05) (either on its
      own or with T3). As with dexamethasone, the thyroid hormones increased the
      response of IGF-I mRNA expression to GH (1 microgram/ml) when added in
      combination with GH (P < 0.001). These observations demonstrate one possible
      mechanism for the interactions of glucocorticoids and thyroid hormones with the
      GH-IGF axis.

PMID- 7561637
TI  - Increased natriuretic peptides in fetal hearts of diabetic rats.
AB  - The main purpose of these studies was to determine whether diabetic pregnancy
      altered maternal and fetal atrial natriuretic peptide (ANP). Diabetes was induced
      in rats by intravenous injection of 40 mg streptozotocin/kg on day 2 of
      gestation. Immunoreactive ANP in plasma, amniotic fluid and hearts on day 20 of
      gestation was measured by radioimmunoassay; fetal cardiac natriuretic peptides
      (ANP, proANP and BNP) were separated by reverse-phase high pressure liquid
      chromatography. Diabetes caused an increase in fetal plasma insulin, placental
      weight, amniotic fluid volume, the ratio of the fetal heart to body weight,
      maternal and fetal plasma ANP, fetal cardiac ANP and fetal cardiac BNP. It is
      suggested that the maternal diabetes-induced increase in fetal ANP might be
      related to fetal myocardial hypertrophy and could contribute to hydramnios.

PMID- 7561638
TI  - Analysis of epidermal growth factor action in human myometrial smooth muscle
      cells.
AB  - The present study investigated the mechanisms involved in the mitogenic action of
      epidermal growth factor (EGF) in cultured human myometrial smooth muscle cells.
      The cells contained EGF/transforming growth factor-alpha (TGF-alpha) receptors as
      well as EGF and TGF-alpha mRNA transcripts and the corresponding proteins.
      Culturing with human EGF resulted in concentration- and time-dependent increases
      in cell density. The maximal increase was seen at 1 nM followed by a decrease to
      control levels at 100 nM EGF. The EGF increased cell density from 4 to 8 days
      followed by a plateau coinciding with the cells reaching confluence. EGF
      treatment concomitantly decreased the average size of cells. TGF-alpha mimicked
      EGF and there was no synergism between the two, suggesting a common mechanism of
      action. Although the presence of 10% fetal bovine serum enhanced overall cell
      growth, it was not required for EGF and TGF-alpha action. The receptor antibody,
      which is directed against the extracellular domain and can inhibit ligand binding
      to the receptors, dramatically inhibited the basal cell growth and exogenous EGF
      reversed the antibody effect. While TGF-alpha antibody was only marginally
      effective, EGF antibody had no effect on basal cell growth. Lavendustin (a
      tyrosine kinase inhibitor), calphostin (a protein kinase C inhibitor), but not H
      89 (a protein kinase A inhibitor), inhibited EGF action. Indomethacin, a cyclo
      oxygenase inhibitor, completely inhibited, whereas nordihydroguaiaretic acid, a
      lipoxygenase inhibitor, slightly inhibited EGF action. While estradiol-17 beta
      modestly inhibited basal as well as EGF-stimulated myometrial smooth muscle cell
      density, progesterone had no effect. In summary, mitogenic action of EGF in human
      myometrial smooth muscle cells does not require serum components and it involves
      tyrosine kinase and protein kinase C signaling and eicosanoids from the
      cyclooxygenase pathway of arachidonic acid metabolism.

PMID- 7561639
TI  - Inverse control of growth hormone and prolactin secretion in clonidine-stimulated
      dairy cattle.
AB  - Clonidine is a specific alpha-2-adrenoreceptor agonist that stimulates growth
      hormone (GH) release in animals and humans. This drug was used to study the GH
      and prolactin (PRL) secretory response in dairy cows and heifers. An i.v.
      infusion of 10 micrograms/kg body weight induced GH release to a peak
      concentration after 30-60 min, while 2 micrograms/kg had no effect on GH
      secretory patterns. Plasma PRL decreased significantly (P < 0.01) starting 15-60
      min after both doses of clonidine, this effect lasting up to 6 h. Clonidine
      significantly lowered plasma insulin (P < 0.01) and raised plasma glucose (P <
      0.01). The changes in plasma GH, PRL, insulin and glucose differed significantly
      between doses, the 10 micrograms/kg dose being more effective (P < 0.01). The
      results of our investigation in dairy cattle provide evidence of (i) an increase
      in GH release after 10 micrograms/kg clonidine; (ii) a concomitant decrease in
      PRL secretion, hence GH and PRL secretion in cattle appear inversely controlled;
      (iii) a significant difference between the effects of the 2 and 10 micrograms/kg
      doses and (iv) no relationship between the changes in plasma GH and PRL after
      clonidine and plasma hormone levels before treatment.

PMID- 7561640
TI  - Interleukin-1 and tumor necrosis factor-alpha increase insulin-like growth factor
      binding protein-3 (IGFBP-3) production and IGFBP-3 protease activity in human
      articular chondrocytes.
AB  - IGF-I is the major anabolic factor for cartilage matrix production. Chondrocytes
      and cartilage treated with interleukin-1 alpha (IL-1 alpha), and chondrocytes
      from several models of inflammatory joint disease, exhibit reduced responsiveness
      to IGF-I. Since the IGF-binding proteins (IGFBPs) modulate the effects of IGF-I,
      we examined the effect of IL-1 alpha and tumor necrosis factor-alpha (TNF-alpha)
      on IGFBP production by normal human articular chondrocytes in primary culture.
      Western ligand blots and immunoprecipitation of conditioned medium samples showed
      that articular chondrocytes produced IGFBPs-2, -3 and -4 and glycosylated IGFBP
      4. Both IL-1 alpha and TNF-alpha increased chondrocyte production of IGFBP-3, but
      did not alter IGFBP-4 production. The activity of a neutral metalloprotease with
      the ability to cleave IGFBP-3 was also increased by IL-1 alpha. These data
      suggest that the cytokines IL-1 alpha and TNF-alpha may act to reduce IGF-I
      access to chondrocytes by increasing production of IGFBP-3. This may be a factor
      in the decreased matrix production in the inflammatory arthritides.

PMID- 7561641
TI  - Changes in calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase
      activity in skeletal muscle of hyper- and hypothyroid rats.
AB  - Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction
      i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases
      remains unclear, but several findings suggest that the catecholamine-beta
      receptor-cAMP system or other messenger systems are disturbed in these diseases.
      In this context, we evaluated changes in the cyclic 3',5'-nucleotide metabolic
      enzyme, cyclic 3',5'-nucleotide phosphodiesterase (PDE) and calmodulin
      concentrations in skeletal muscles of hyper- and hypothyroid rats. Activities of
      cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats,
      and calmodulin concentration was high in hyperthyroid and low in hypothyroid
      rats, as compared with normal rats. DE-52 column chromatographic analysis showed
      that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in
      peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in
      peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in
      hyperthyroid rats, but the activities in peaks I and II were unchanged. These
      findings indicate that cAMP and calmodulin may have some role in skeletal muscle
      function in the hyperthyroid state, and that cAMP and calmodulin-dependent
      metabolism may be suppressed in the hypothyroid state.

PMID- 7561642
TI  - Further studies on the regulation, localization and function of the TRH-like
      peptide pyroglutamyl-glutamyl-prolineamide in the rat anterior pituitary gland.
AB  - Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity
      in the rat anterior pituitary gland is accounted for by the TRH-like tripeptide
      pyroglutamyl-glutamyl-prolineamide (pGlu-Glu-ProNH2, < EEP-NH2). The present
      study was undertaken to investigate further the regulation, localization and
      possible intrapituitary function of < EEP-NH2. Anterior pituitary levels of < EEP
      NH2 were determined between days 5 and 35 of life, during the oestrous cycle and
      after treatment with the luteinizing hormone-releasing hormone (LHRH) antagonist
      Org 30276. Treatment of adult males with the LHRH antagonist either for 1 day
      (500 micrograms/100 g body weight) or for 5 days (50 micrograms/100 g body
      weight) reduced anterior pituitary < EEP-NH2 levels by 25-30% (P < 0.05 versus
      saline-treated controls). Anterior pituitary < EEP-NH2 increased between days 5
      and 35 of life. In females, these levels were 2- to 3-fold higher (P < 0.05) than
      in males between days 15 and 25 after birth; these changes corresponded with the
      higher plasma follicle-stimulating hormone (FSH) levels in the female rats. After
      day 25, < EEP-NH2 levels in female rats decreased in parallel with a decrease in
      plasma FSH. Injections with the LHRH antagonist (500 micrograms/100 g body
      weight), starting on day 22 of life, led to reduced contents of < EEP-NH2 in the
      anterior pituitary gland of female rats on days 26 and 30 (55 and 35% decrease
      respectively). Levels of < EEP-NH2 in the anterior pituitary gland did not change
      significantly during the oestrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561643
TI  - The in vivo effects of fibroblast growth factor and epidermal growth factor on
      the secretion of oestradiol, androstenedione and progesterone by the
      autotransplanted ovary in the ewe.
AB  - An experiment was conducted to determine the effects of epidermal growth factor
      (EGF) and fibroblast growth factor (FGF), infused into the ovarian artery, on the
      secretion of ovarian steroids during the mid-luteal phase in ewes with an
      autotransplanted ovary. The infusion of EGF (5 micrograms/h) for 12 h suppressed
      the secretion of oestradiol and androstenedione during the infusion and for up to
      30 h after the infusion. The secretion of progesterone tended to be lower
      immediately after the infusion (not significant) but had recovered by 24 h after
      the end of the infusion and then increased significantly (P < 0.05) to rates
      higher than in control animals. There were no effects of the infusion of EGF on
      the characteristics of pulsatile LH secretion. FSH concentrations increased 24 h
      after the end of the infusion probably as an indirect consequence of the changes
      in oestradiol secretion and not as a consequence of a direct effect of EGF on the
      hypothalamo-pituitary axis although this latter possibility cannot be
      unequivocally eliminated. The infusion of FGF (1.5 microgram/h) for 12 h also
      suppressed the secretion of oestradiol and androstenedione during and for up to
      30 h after the infusion. The infusion of FGF had no detectable effect on the
      secretion of progesterone or the characteristics of pulsatile LH secretion. FSH
      concentrations increased steadily during the infusion but declined rapidly to
      below pre-infusion concentrations after the end of the infusion. These data
      provide tentative in vivo evidence for paracrine and autocrine effects of EGF and
      FGF on follicular and luteal function in sheep.

PMID- 7561644
TI  - Expression of the prolactin receptor gene during the breeding and non-breeding
      seasons in red deer (Cervus elaphus): evidence for the expression of two forms in
      the testis.
AB  - The red deer is a seasonally breeding mammal with a circannual cycle of prolactin
      secretion which reaches its peak during the non-breeding season. This study
      investigated expression of the prolactin receptor gene in red deer tissues
      collected in the breeding and non-breeding seasons. A 562 bp fragment of the
      extracellular domain of the red deer prolactin receptor cDNA was amplified from
      red deer liver poly(A)+ RNA by reverse transcriptase-polymerase chain reaction
      (RT-PCR) using primers designed from the human sequence. Northern blots were
      prepared using 10-20 micrograms poly(A)+ RNA. The blots were hybridized to the
      562 bp cDNA labelled by random priming with alpha 32P-dCTP. A main transcript of
      3.5 kb was expressed in liver, heart, kidney and testis throughout the year and
      in epididymis during the breeding season only. In the testis an additional major
      transcript of 1.7 kb was present during the breeding and non-breeding seasons.
      Competitive binding assays using 125I-ovine prolactin (125I-oPRL) were performed
      on microsomal membrane fractions prepared from liver. Scatchard analyses
      confirmed the presence of a single class of lactogen-binding receptor with a mean
      Ka of 0.87 +/- 0.12 x 10(9) M-1 and a Bmax of 73.6 +/- 9.8 fmol/mg protein (n =
      5). Cross-linking of 125I-oPRL to liver microsomes with 0.5 mM disuccinimidyl
      suberate followed by SDS-PAGE revealed a major band of molecular mass 56 kDa
      which was displaced by ovine prolactin, suggesting a specific lactogen-binding
      entity of 33 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561645
TI  - Inhibin and oestradiol-17 beta in antral follicles of various size classes of
      cyclic rats.
AB  - On the various days of the 5-day oestrous cycle of the rat, ovarian antral
      follicles were dissected out and grouped in five size classes. Four follicles of
      the same size class were homogenized jointly in medium, after which inhibin-like
      bioactivity, inhibin immunoreactivity and oestradiol-17 beta content were
      measured. In general, there was a significant correlation between immunologically
      and biologically active inhibin levels in the different size classes; overall
      correlation was 0.85 (n = 87, P < 0.00001). In the smallest antral follicles
      (classes 1 and 2) inhibin bioactivity was detected only during the first three
      days of the cycle. With increasing follicle size, inhibin bioactivity and
      immunoreactivity increased, with maximal activity present in the largest, i.e.
      preovulatory, follicles (class 5) during the last three days of the cycle (the
      day of oestrus denotes day 1 of the cycle). These results indicate that only
      follicles which reach the antral stage at oestrus, and are known to be recruited
      by the periovulatory FSH peak, acquire the potency to produce biologically active
      inhibin. This is the cohort of follicles from which selection of ovulatory
      follicles will normally take place. In contrast to inhibin, follicular oestradiol
      17 beta concentrations were negligible until the last days of the cycle when
      oestradiol-17 beta was present in follicles larger than class 2; levels increased
      with increasing follicle size and a maximal level was found in preovulatory
      follicles at pro-oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561646
TI  - The effects of oestradiol and relaxin on extensibility and collagen organisation
      of the pregnant rat cervix.
AB  - The effects of exogenously introduced oestradiol-17 beta (E) and relaxin (RLX) on
      cervical extensibility and collagen organisation were tested in rats
      ovariectomised in late pregnancy. When the cervices were stretched in vitro by 1
      mm increments, it was found that those from rats given E alone generated
      significantly higher tensions than those from control rats, while cervices from
      rats given both E and RLX had tensions similar to controls. Examination of
      cervical sections under the light microscope and ultra-thin sections under the
      electron microscope showed that the collagen fibres in the cervices from E
      treated rats were highly organised, whereas those from animals given E+RLX and
      control animals were disorganised and dispersed. It was concluded that E
      decreased cervical extensibility, while RLX counteracted the effect of E to
      maintain a soft and easily extensible cervix.

PMID- 7561647
TI  - Functional and morphological changes of the thyroid gland following 5 days of
      pulsatile TRH stimulation in male rats.
AB  - The aim of the present study was to evaluate in vivo the selective effects of a
      small increase in plasma TSH levels on thyroid function, proliferation and
      morphology. Chronically catheterized male Sprague-Dawley rats were stimulated
      i.v. over 5 days either with TRH (2 micrograms TRH in 100 microliters 0.9% (w/v)
      NaCl (TRH-P) or the NaCl carrier alone (P), both given as pulses every 2 h.
      Control groups were cotreated i.v. with 10 micrograms thyroxine (T4)/100 g body
      weight per day (TRH-P + T4) starting 2 days before pulsatile stimulation. TSH
      plasma levels were approximately doubled by TRH-P (P < or = 0.001), T4 plasma
      levels significantly increased (P < or = 0.001) but tri-iodothyronine plasma
      levels did not change compared with treatment with P. No significant changes
      between groups were found in thyroid weight and in intrathyroidal iodine content,
      but the percentage of 5-bromo-2'-desoxyuridine-labelled thyrocytes as a marker of
      proliferation in TRH-P-treated animals was significantly increased over P or TRH
      P + T4 (P < or = 0.001). Ultrastructural analysis of the thyroid evaluated by
      electron microscopy revealed a significant increase in the number of lysosomes (P
      < or = 0.001). The size of the endoplasmic reticulum (ER) in relation to the
      cytoplasm was significantly increased when treated with TRH-P compared with P or
      TRH-P + T4 (P < or = 0.001). Post-embedding immunogold staining revealed Tg as a
      major product within ER cisternae. Immunogold labelling was moderate in controls
      and higher densities of gold particles were obtained in TRH-P-treated animals (P
      < or = 0.001). In conclusion, short-term pulsatile TRH stimulation increasing the
      plasma levels of immunoreactive TSH only twofold is capable of inducing
      hypertrophy of the thyrocytes by gross ultrastructural changes which are
      paralleled by an increase in circulating T4. These data underscore the dominant
      role of TSH on thyroid ultrastructure within the narrow boundaries of normal
      physiological regulation.

PMID- 7561648
TI  - Follicular development, steroidogenesis and gonadotrophin secretion in response
      to long-term treatment with a gonadotrophin-releasing hormone agonist in the rat.
AB  - Gonadotrophin-releasing hormone (GnRH) and its agonists are implicated in the
      local control of rat ovarian function. We have evaluated the effects of long-term
      administration of different doses of GnRH agonist (GnRH-Ag) in vivo (a) on
      reproductive cyclicity and follicular development, (b) on peripheral
      gonadotrophin and steroid concentrations and (c) on in vitro cAMP and
      progesterone production by the follicles in response to stimulatory doses of FSH
      or LH (1 microgram/ml). GnRH-Ag (0.2, 1 or 5 micrograms/day) administration for
      28 days had a profound impact on the oestrous cycle of rats as revealed by
      vaginal cytology. GnRH-Ag treatment caused a decrease in ovarian and uterine
      weights, which correlated very well with the decrease in the number of follicles
      present in the ovary. GnRH-Ag (5 micrograms/day) reduced the number of early
      preantral follicles and there was complete disappearance of early as well as late
      antral follicles. However, a dose of 1 microgram GnRH-Ag/day was effective in the
      complete demise of only late antral follicles with a significant attenuation in
      the number of early antral follicles. There was an enhancement in serum LH
      concentrations in response to the highest dose of GnRH-Ag administration with
      serum FSH concentrations declining in rats treated with the two higher doses.
      However, serum prolactin concentrations were attenuated only in rats treated with
      the highest dose of GnRH-Ag. GnRH-Ag treatment decreased serum progesterone and
      oestradiol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561650
TI  - Bacterial leakage of mineral trioxide aggregate as a root-end filling material.
AB  - Previous dye leakage studies have shown that mineral trioxide aggregate leaks
      significantly less than other commonly used root-end filling materials. This
      study determined the time needed for Staphylococcus epidermidis to penetrate a 3
      mm thickness of amalgam, Super-EBA, Intermediate Restorative Material (IRM), or
      mineral trioxide aggregate (MTA) as root-end filling materials. Fifty-six single
      rooted extracted human teeth were cleaned and shaped using a step-back technique.
      Following root-end resection, 48 root-end cavities were filled with amalgam,
      Super-EBA, IRM, or MTA. Four root-end cavities were filled with thermoplasticized
      gutta-percha without a root canal sealer (+ control), and another four were
      filled with sticky wax covered with two layers of nail polish (- control). After
      attaching the teeth to plastic caps of 12-ml plastic vials and placing the root
      ends into phenol red broth, the set-ups were sterilized overnight with ethylene
      dioxide gas. A tenth of a microliter of broth containing S. epidermidis was
      placed into the root canal of 46 teeth (40 experimental, 3 positive, and 3
      negative control groups). In addition, the root canals of two teeth with test
      root-end filling materials and one tooth from the positive and negative control
      groups were filled with sterile saline. The number of days required for the test
      bacteria to penetrate various root-end filling materials was determined. Most
      samples whose apical 3 mm were filled with amalgam, Super-EBA, or IRM began
      leaking at 6 to 57 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561649
TI  - Influence of treatment with the anti-oestrogen 3-hydroxytamoxifen (droloxifene)
      on plasma sex hormone levels in postmenopausal patients with breast cancer.
AB  - Plasma levels of oestradiol (Oe2), oestrone (Oe1) oestrone sulphate (Oe1S),
      androstenedione, testosterone, dehydroepiandrosterone (DHEA),
      dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG) and
      the gonadotrophins (FSH and LH) were determined in 20 postmenopausal women with
      breast cancer treated with the anti-oestrogen droloxifene (3-hydroxytamoxifen).
      Plasma oestrogens were measured before and after 3, 6 and 12 months of therapy.
      The other hormones were measured before and after 6 months of therapy.
      Droloxifene treatment had no significant influence on plasma levels of Oe2.
      Plasma levels of Oe1 and Oe1S increased during treatment (mean increase of 11.9
      15.9% and 24.5-69.4% respectively after different time-intervals on treatment).
      The Oe1S/Oe1 and Oe1S/Oe2 ratios increased by mean values of 13.8-45.2% and 25.9
      52.4% respectively. Plasma SHBG increased significantly by a mean value of 73.9%,
      while FSH and LH fell non-significantly by 19.7% and 20.4% respectively. Plasma
      levels of testosterone, androstenedione, DHEA and DHEAS all increased during
      treatment, but none of these alterations were of statistical significance. While
      the influence of droloxifene on plasma SHBG resembled that which is seen during
      treatment with tamoxifen, its influence on plasma oestrogens and the
      gonadotrophins seems to be different. Possible explanations of such differences
      and the clinical implications of alterations in plasma hormones during treatment
      with droloxifene are discussed.

PMID- 7561651
TI  - Scanning electron microscopic evaluation of root-end preparations.
AB  - The use of an ultrasonic apical preparation technique has been advocated
      recently. Root-end preparations in 30 extracted single-canaled human teeth were
      evaluated, comparing those prepared with ultrasonic instrumentation alone, or in
      combination with rotary bur preparation, to those prepared with rotary
      instrumentation alone. Specimens were evaluated for the presence of debris, smear
      layer, and the smoothness and uniformity of the preparations. The apical
      preparations were completed according to the varying techniques, examined, and
      photographed under scanning electron microscopy. Those cavities prepared with the
      ultrasonic, either alone or in combination with rotary instrumentation, showed
      the presence of significantly less smear layer compared with those made by burs
      alone. Cavities prepared with ultrasonic instrumentation in combination with
      rotary instrumentation contained significantly less debris than those prepared
      with rotary instrumentation alone. There were no significant differences between
      the techniques in the smoothness or uniformity of the preparations.

PMID- 7561652
TI  - Detection of interleukin-1 beta mRNA in rat periapical lesions.
AB  - Cells expressing interleukin-1 beta (IL-1 beta) mRNA were demonstrated by in situ
      hybridization in rat periapical lesions. A great number of osteoclasts with
      significant tartrate-resistant acid phosphatase activity were observed on the
      bone surfaces, and numerous IL-1 beta mRNA-expressing cells were widely
      distributed in the periodontal ligaments. IL-1 beta mRNA-expressing cells were
      mainly observed around the blood vessels in the vicinity of the bone resorption
      sites and occasionally found near the osteoblasts. Immunohistochemistry and
      enzyme histochemistry assays showed that IL-1 beta mRNA-expressing cells were not
      bone cells, but that they had the characteristic features of macrophages. These
      results suggested that macrophages may contribute to the production of IL-1 beta
      and play an important role in activation of osteoclastic bone resorption.

PMID- 7561654
TI  - Effects of lipopolysaccharides on human dental pulp cells.
AB  - Human dental pulp cells were treated with 1, 10, and 100 micrograms/ml of
      lipopolysaccharide (LPS). The effects of treatment were examined by measurement
      of the DNA content, protein content, and alkaline phosphatase activity of the
      cells. LPS samples were purified from Porphyromonas gingivalis, Porphyromonas
      endodontalis, and Fusobacterium nucleatum isolated from root canals, and
      Escherichia coli 0111:B4 LPS was used as a positive control. At a concentration
      of 1 microgram/ml, none of the LPSs caused any change in the production of DNA or
      protein, whereas the amount of DNA was increased at 10 micrograms/ml and
      inhibited at 100 micrograms/ml. Protein synthesis was decreased by LPSs at both
      10 and 100 micrograms/ml. Alkaline phosphatase activity was not changed at any
      concentration of LPS tested.

PMID- 7561653
TI  - Experimental study of the biocompatibility of four root canal sealers and their
      influence on the zinc and calcium content of several tissues.
AB  - Four root canal sealers (AH-26, Roth 811, CRCS, and Sealapex) were tested for
      tissue biocompatibility in rat connective tissue. Each sealer was placed in
      Teflon tubes and implanted subcutaneously in Wistar-Furth rats. The implants were
      removed after 7, 14, and 21 days, fixed, and histologically prepared for
      microscopical evaluation. Brain, liver, kidneys, and uterus were removed from the
      animals killed at the first experimental period (7 days) and analyzed for zinc
      and calcium concentration by flame atomic absorption spectrophotometry. In total,
      100 specimens were examined. At the seventh day, the most irritant material was
      seen to be AH-26, but this inflammatory reaction decreased with time. Roth 811
      and Sealapex caused moderate-to-severe inflammatory reaction, whereas CRCS caused
      mild to moderate. CRCS and Roth 811 induced redistribution of zinc, whereas AH-26
      induced changes in calcium content in some organs.

PMID- 7561655
TI  - Quantitative analysis of immunoglobulins and inflammatory factors in human pulpal
      blood from exposed pulps.
AB  - The levels of immunoglobulins (IgG, IgA, and IgM) and inflammatory factors
      (elastase, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, interleukin
      6, and tumor necrosis factor-alpha) in the blood of human dental pulp were
      quantified, using enzyme-linked immunosorbent assays. The pulpal blood samples
      were obtained with nylon fiber pellets from normal and inflamed dental pulp at
      pulp sites exposed on pulpectomy. Statistically significant differences between
      normal and inflamed pulp were found in the levels of IgG (p < 0.01), IgA (p <
      0.05), IgM (p < 0.01), elastase (p < 0.05), and prostaglandin E2 (p < 0.01).
      These findings indicate that these factors play an important role in the
      pathogenesis of pulpal disease, and the sampling methods used in this study are
      useful for examination of pulpal inflammation.

PMID- 7561656
TI  - Histopathological observations of periapical repair in teeth with radiolucent
      areas submitted to two different methods of root canal treatment.
AB  - Dogs' teeth with induced chronic periapical periodontitis were treated
      endodontically by two different methods, and the results were compared. A total
      of 40 root canals from the upper and lower premolars of two dogs were prepared
      chemomechanically. In method 1, a high-concentration (5.25%) hypochlorite
      solution was used during the instrumentation of the root canal, and an
      antibacterial dressing was applied between sessions, followed by filling of the
      root canal. In method 2, a low-concentration (0.5%) sodium hypochlorite solution
      was used as an adjunct to mechanical debridement, and the root canal was filled
      during the same session. The histopathological results showed that method 1 led
      to better periapical repair than method 2.

PMID- 7561657
TI  - Effect of dentin preparation and acid etching on the sealing ability of glass
      ionomer and composite resin when used to repair furcation perforations over
      plaster of Paris barriers.
AB  - Access openings and furcation perforations were prepared in 60 human extracted
      teeth and randomly divided into four equal groups. Plaster of Paris barriers were
      created in all perforations. The defects were obturated using either glass
      ionomer or composite resin with or without acid etching of the dentin. The pulp
      chambers and access openings were filled with composite resin. After immersion in
      2% methylene blue solution for 2 weeks, the teeth were sectioned longitudinally
      and dye penetration was measured under a stereomicroscope using the NIH Image
      1.47 Macintosh program. The results indicated that light-cured glass ionomer
      provided a significantly better seal than did the light-cured composite resin
      with or without dentin preparation and acid etching. The glass ionomer allowed
      significantly less dye penetration when used on etched dentin than it did on
      nonetched dentin.

PMID- 7561658
TI  - A comparison of root canal preparations using Ni-Ti hand, Ni-Ti engine-driven,
      and K-Flex endodontic instruments.
AB  - This study used a modified Bramante technique and new digital subtraction
      software to compare root canals prepared by nickel-titanium (Ni-Ti) hand, Ni-Ti
      engine-driven, and stainless steel hand endodontic instruments. Sixty mesial
      canals of extracted human mandibular molars were randomly divided into five
      groups. The roots were embedded in clear resin and cross-sectioned in the apical
      and mid-root areas. In group A, canals were instrumented using a quarter
      turn/pull technique with K-Flex files. In group B, canals were prepared with Ni
      Ti hand files (Mity files) using the same technique as in group A. Group C was
      prepared with NT Sensor engine-driven files. Group D canals were prepared with Ni
      Ti Canal Master "U" hand instruments. Group E was prepared with engine-driven Ni
      Ti Lightspeed instruments. Digitized images of the uninstrumented canals were
      compared with images of the instrumented canals. Engine-driven Ni-Ti instruments
      (Lightspeed and NT Sensor file) and hand instrumentation with the Canal Master
      "U" caused significantly less canal transportation (p < 0.05), remained more
      centered in the canal (p < 0.05), removed less dentin (p < 0.05), and produced
      rounder canal preparations than K-Flex and Mity files. Engine instrumentation
      with Lightspeed and NT Sensor file was significantly faster than hand
      instrumentation (p < 0.05).

PMID- 7561659
TI  - Influence of plugger penetration on the sealing ability of vertical condensation.
AB  - This study sought to evaluate the influence of plugger penetration on the sealing
      ability of vertical compaction. Ninety anterior teeth were used. After cleaning
      and shaping to a size #30 file, these teeth were divided into three equal groups
      (A, B, and C) according to the level of plugger penetration set at 5, 7, and 9 mm
      short of the working length, respectively. Then vertical compaction was
      performed. Apical microleakage was determined using pressurized fluid filtration
      at 90 min, 1 day, and 1, 4, 12, 18, and 24 wk after root canal obturation.
      Leakage tended to increase over time for the three groups. The deeper plugger
      penetration groups (A and B) showed significantly less apical leakage than group
      C.

PMID- 7561660
TI  - Canal blockage and debris extrusion with eight preparation techniques.
AB  - The objective of this study was to assess and compare canal blockages and apical
      extrusion of dentin debris during canal shaping with eight preparation
      techniques. A total of 208 canals in extracted human teeth were prepared by one
      operator using one type of file. The techniques included were standardized,
      stepback with reaming, stepback with circumferential filing, stepback with
      anticurvature filing, double-flare, stepdown, crown-down pressureless, and
      balanced force. Records were kept of the number of canals that became permanently
      blocked with debris at some stage during preparation. Dentin debris extruded
      apically was collected in preweighed containers and the dry weight of debris
      determined to 10(-5) g precision. Blockages varied significantly among techniques
      (p < 0.001) and occurred most frequently in canals prepared with the stepback
      techniques with anticurvature (n = 19) and circumferential filing (n = 16) and
      least in the balanced force technique (n = 0). Apical extrusion occurred in 169
      of the 208 roots, but there were no significant differences in the incidence of
      extrusion among techniques. The weight of extruded dentin did vary significantly
      among techniques (p < 0.05), with most extrusion occurring with the stepback
      techniques with circumferential (0.71 mg) and anticurvature (0.69 mg) filing and
      the least extrusion with the balanced force (0.38 mg) and crown-down pressureless
      (0.46 mg) techniques. Under the conditions of this study, it is concluded that
      techniques involving a filing (linear) motion caused significantly more blockages
      and extruded significantly more apical dentin debris.

PMID- 7561662
TI  - A new focus for endodontics.

PMID- 7561661
TI  - Coronal leakage and treatment failure.
AB  - This report presents a case in which undiagnosed coronal leakage resulted in
      failure in the endodontic management of a tooth. Coronal leakage occurred during
      root canal treatment as a result of the presence of deficient composite resin
      fillings and secondary caries. Despite repeated visits of cleaning and dressing,
      the canal continued to be contaminated and symptoms persisted. On referral, the
      reason for treatment failure was diagnosed. The tooth was successfully treated by
      the replacement of the deficient fillings, after the elimination of underlying
      caries. Symptoms resolved enabling the completion of the root canal treatment.

PMID- 7561663
TI  - Influenza in Madrid, Spain, 1991-92: validity of the sentinel network.
AB  - OBJECTIVES: The aim was, firstly, to study the validity of the sentinel network
      data by analysing the correlation between the weekly influenza cases detected by
      the network and the number of cases notified to the compulsory disease
      notification system and, secondly, to describe the epidemiology of the period
      1991-92 in terms of the sentinel network data. DESIGN: The study design was
      descriptive. SUBJECTS: The population resident in the city of Madrid. MAIN
      RESULTS: There was a high correlation between the cases notified to the
      compulsory disease notification system and those listed by the sentinel network
      (r = 0.91, p < 0.001, r2 = 0.82). The epidemic activity during the period 1991-92
      was centred approximately on week 48 in 1991 and week 6 in 1992 (24 November 1991
      8 February 1992). Altogether 913 cases of influenza were notified through the
      sentinel network. The greatest number of cases occurred in people aged between 20
      and 39 years. CONCLUSION: For the epidemiological surveillance of influenza it is
      necessary to develop systems that can quickly detect epidemic periods and provide
      information about populations at risk, in addition to systems that isolate and
      identify seasonal epidemic viruses. Both types of data will help the development
      of adequate public health policies. Sentinel networks provide these data and
      offer additional advantages such as lower cost.

PMID- 7561664
TI  - Organochlorine residues in human breast milk: analysis through a sentinel
      practice network.
AB  - STUDY OBJECTIVE: The study aimed to assess through a sentinel practice network
      the validity of data on levels of organochlorine residues in human milk along
      with personal, lifestyle, and exposure variables of breastfeeding women; to
      compare the results of this new approach with those of the Lower Saxony breast
      milk surveillance programme; and to test hypotheses on potential determinants of
      contamination levels. DESIGN: Eligible women were enrolled into this cross
      sectional study by a network of 51 paediatric practices when bringing their
      babies for a U3 infant screening examination (4th to 6th week after delivery).
      Lifestyle and exposure factors were obtained by questionnaire. All milk samples
      were analysed for hexachlorocyclohexane, hexachlorbenzole, DDT, dieldrin,
      polychlorinated biphenyls (PCB) and heptachlor; half the samples were also
      analysed for dioxin. Analytic statistics were computed using polychotomous
      logistic regression (PLR). SETTING: The study was conducted in Lower Saxony,
      Germany, from summer 1992 to summer 1993. PARTICIPANTS: Altogether 156
      primiparous, breast feeding German women, aged 25-35 years, who had been born and
      had grown up in West Germany, were studied. MAIN RESULTS: Compared with the
      regular programme, participants in this study had their milk analysed sooner
      after delivery and were more likely to have grown up in rural areas, less likely
      to have been exposed to hazardous substances, less likely to have a diet of
      health food, and slightly less likely to be a smoker at the time of the study.
      Breast milk contamination levels were comparable in both studies, and in all but
      two cases well below the tolerable concentrations established by the Deutsche
      Forschungsgemeinschaft (German Research Fellowship). After adjustment for
      potential confounders using polychotomous logistic regression, there were
      statistically significant positive associations between breast milk contamination
      and age (PCB, test for trend: p = 0.006), average dietary fat intake per week
      (dioxin, p = 0.01), and proximity of residence to hazardous sites (dioxin, p <
      0.05), and negative associations between residue levels and relative body weight
      at the time of the study (PCB; p < 0.0001) and difference in body weight (weight
      minus weight before the pregnancy; PCB, p = 0.0002), respectively. CONCLUSIONS:
      Sentinel practice networks are a feasible and low-biased approach to population
      based breast milk studies. The contamination levels and associations found are
      biologically plausible and comparable with the results of other studies. To
      reduce organochlorine residue levels in human milk in the short term, breast
      feeding women should be advised not to try to reduce their weight until after
      lactation. Public promotion of a lower dietary fat intake may reduce the lifetime
      accumulation of organochlorine compounds in the human body fat tissue in the long
      term, resulting in lower concentrations in breast milk as well.

PMID- 7561665
TI  - General practice data retrieval: the Northern Ireland project.
AB  - OBJECTIVE: To develop an epidemiological database of morbidity in the community
      as presented to general practitioners and to support epidemiological research in
      general practice. DESIGN: The project is a sentinel network of 23 general
      practices in Northern Ireland that report the incidence of a list of selected
      diseases to a central unit for analysis. RESULTS: Results are presented for
      depression, diabetes, and myocardial infarction. The age--sex distributions of
      diabetes and myocardial infarction are comparable with other published data but
      the incidence of depression is under estimated. CONCLUSIONS: The importance of
      complete accuracy of data reported within sentinel networks depends on the
      purposes for which information is to be used. For some diagnoses, such as
      diabetes and acute myocardial infarction, the accuracy of the reported incidence
      is high while for other diseases, such as depression, where diagnostic behaviour
      varies more between doctors, the figures are much less reliable.

PMID- 7561666
TI  - Denominator estimation: approaches in the Hamburg paediatric sentinel network.
AB  - STUDY OBJECTIVE: The aims were to develop an estimator for the size of paediatric
      practices to be used as a denominator for purposes of comparison; to analyse the
      age structure of the patients attending paediatric practices and to check the
      necessity for an age specific denominator; and to validate the denominator
      information by other available data. DESIGN: This was an observational study.
      SETTING/PARTICIPANTS: A sentinel network was set up comprising 26 self selected
      paediatric practices. Weekly patient contacts in relation to age and sex were
      counted three times during the study period of two years. In addition, accounting
      data, including the total number of children treated in a given three month
      period (quarter), were available. MAIN RESULTS: Weekly patient contact counts
      were stable over time, not in terms of the absolute number of contacts but in the
      rank positions of the practices (rs = 0.86) and in their age structure. The age
      distribution of weekly patient contacts differed significantly between the
      practices. Cross validation of the weekly contact count by means of the quarterly
      accounting data resulted in a rank correlation of rs = 0.90. CONCLUSIONS:
      Sentinel networks with paediatric practices should use age specific denominator
      information. Weekly contact group, estimated by counts in a sample of weeks, is a
      stable and easily available denominator for sentinel practices in the context of
      the German health care system.

PMID- 7561667
TI  - Validating long term morbidity recording.
AB  - STUDY OBJECTIVE: To assess the validity of diagnosis made in a general practice
      based morbidity recording from 1967-90. DESIGN: Clinical features of patients
      with a diagnosis of migraine headache and diabetes mellitus were compared with
      international diagnostic criteria for these conditions. For migraine headache the
      International Classification of Health Problems in Primary Care (ICHPPC)
      definition was used, while diabetes mellitus was defined according to World
      Health Organization (WHO) criteria. SETTING: The continuous morbidity registry of
      the Department of General Practice and Social Medicine, University of Nijmegen,
      has been recording data from four general practices (12,000 patients)
      continuously since 1967. The database is used for longitudinal clinical research.
      PATIENTS: All patients with migraine headache and living in the practice area at
      the time of study and matched controls with tension headache received a
      questionnaire asking about ICHPPC criteria symptoms of migraine. The medical
      records of all patients with diabetes mellitus at the time of diagnosis were
      compared with WHO criteria. MAIN RESULTS: In 85% of patients with migraine
      headache, the questionnaire confirmed the ICHPPC defined criteria. Twenty nine
      per cent of the matched controls reported migraine features. In 74% of the
      patients with diabetes mellitus the diagnosis was made in agreement with the WHO
      criteria: in 12% no clinical information from the time of diagnosis could be
      traced. CONCLUSIONS: The diagnoses of migraine headache and diabetes mellitus in
      the registry largely agreed with international criteria. The quality control of
      recorded data is satisfactory, and the registry might serve as a model for other
      primary care based databases.

PMID- 7561668
TI  - Effects of the German 1993 health reform law upon primary care practitioners'
      individual performance: results from an empirical study in sentinel practices.
AB  - An empirical study in Lower Saxony aimed to investigate any changes in primary
      care physicians' diagnostic and therapeutic strategies as a result of Germany's
      1993 health reform act (known as the Gesundheitsstruktur Gesetz or GSG), which
      included the countrywide implementation of a strict drug budget. A sentinel
      network consisting of a 37% sample of 350 randomly selected doctors (n = 130,
      GPs, general internists) was established in Lower Saxony. Four cross sectional
      surveys, each focussing on one group of health problems, were carried out during
      1993. These aimed to show whether sentinel practice networks are suitable for
      reporting physicians' attitudes towards health care cost containment policies
      and, secondly, changes in physicians' quantitative and qualitative assessments of
      the 1993 reform act during its first year of implementation. Participating
      physicians reported patient consultations (n = 3728). Standardised questionnaires
      ascertained sociodemographic variables and major reasons for the patients' visit.
      Data on the diagnoses associated with the patient's main reason for the
      consultation, the doctor's assessment of the severity of the problem, and
      diagnostic and treatment strategies were also recorded. The questionnaire
      focussed on changes in therapy made by the physician together with the reasons
      for these changes. A number of treatment changes made with regard to cost
      containment were recorded. During the course of 1993 a decrease in reported
      changes in treatment was noticed. As expected, some doctors recorded a reduction
      in successful outcomes of treatment and ascribed this to the reform act.
      Differences between the four surveys with regard to the influence of the health
      reform act on the frequency of changes in treatment and the physicians'
      expectations cannot be explained sufficiently by the physicians' adaptation to
      the cost containment policies within the year.

PMID- 7561669
TI  - Measles, mumps, and rubella: monitoring in Switzerland through a sentinel
      network, 1986-94. Sentinella Arbeitsgemeinschaft.
AB  - STUDY OBJECTIVES: Since 1986, the national sentinel network in Switzerland
      (Sentinella) has collected reports of measles, mumps, and rubella cases in order
      to evaluate the impact of the Swiss MMR vaccination campaign (started in 1987) on
      disease frequency. DESIGN: Passive surveillance of clinical measles, mumps, and
      rubella cases through a voluntary physician based sentinel network in
      Switzerland. SETTING: Each year between June 1986 and May 1994, 150 to 200
      general practitioners, specialists in internal medicine, and paediatricians in
      private practice covering the whole country have reported weekly numbers of
      consultations. PATIENTS: Every patient who fulfilled the case definition and
      consulted a physician participating in the Sentinella network was reported. MAIN
      RESULTS: Since 1986, the annual number of reported measles cases per physician
      has fallen--from 1.3 (95% confidence interval (CI) 1.11, 1.50) in 1986-87 to 0.4
      (95% CI 0.30, 0.50) in 1993-94. A decreasing trend, although less pronounced, was
      also observed for rubella. An initial decrease in mumps cases was reported--from
      1.8 (95% CI 1.57, 2.03) annually reported cases per physician in 1986-87 to 0.7
      (95% CI 0.55, 0.83) in 1989-90. This was followed, however, by a net and
      sustained increase. In 1993-94, the mean annual number of reported mumps cases
      per practitioner reached 4.7 (95% CI 4.34, 5.01) which was the highest level
      since surveillance had started. Over the whole eight year period, reported mumps
      cases, in terms of the percentage of consultations, were four times more frequent
      in the French speaking part of Switzerland than in the rest of the country. The
      proportion of mumps cases in people reported to have been vaccinated also
      increased--from 10% in 1986-87 to 60% in 1993-94. CONCLUSIONS: Reductions in
      cases of measles and rubella but an appreciable increase in mumps cases have been
      observed in the past three years in Switzerland. This findings, combined with
      increasing vaccination coverage and the fact that 60% of mumps cases are reported
      in vaccinated people, suggests that the overall efficacy of the mumps vaccines
      used in Switzerland is probably below 80%. Under these conditions the goal of
      eliminating mumps will probably not be reached. Further studies are needed to
      evaluate the efficacy of the different mumps vaccines used.

PMID- 7561670
TI  - Influenza surveillance: experiences from establishing a sentinel surveillance
      system in Germany.
AB  - OBJECTIVES: Before and during peak influenza periods there is increased morbidity
      from other respiratory tract disorders. Sentinel networks of primary care
      physicians can be very effective in the early detection of influenza epidemics
      and the German network, the Arbeitsgemeinschaft Influenza (AGI), began its work
      in this area in 1992. METHODS: Data are transmitted weekly from the doctor's
      computer via Btx to a central computer. The numerator is the weekly number of
      acute respiratory infections (ARI) in five age groups and the denominator is the
      weekly number of patient consultations. Data on hospitalisation, mortality, and
      days of sick leave from work or school are also collected. Swabs for influenza
      specimens are collected in 30 physicians' offices each Monday and sent to three
      reference centres. FINDINGS: During the last recording period, from week 46 1993
      to week 15 1994, 411 physicians' offices participated in the network. For 16 to
      22 weeks, more than 60% of the participants transmitted data. During both the
      1992-93 and 1993-94 influenza seasons, peaks were observed in the rate of ARI.
      There was a corresponding increase in sick leave from work and school. Rates for
      hospitalisation and deaths due to influenza showed no peaks during either season.
      CONCLUSIONS: Although the German sentinel network for influenza experienced some
      technical problems in the first year, it was possible to solve these. Reporting
      rates were very satisfactory in the second year. The network will now be expanded
      to include 750 physicians in order to receive 600 weekly reports and obtain a
      solid baseline for an early warning system.

PMID- 7561671
TI  - Soft commitment: self-control achieved by response persistence.
AB  - With reinforcement contingent on a single peck on either of two available keys
      (concurrent continuous reinforcement schedules) 4 pigeons, at 80% of free-feeding
      weights, preferred a smaller-sooner reinforcer (2.5 s of mixed grain preceded by
      a 0.5-s delay) to a larger-later reinforcer (4.5 s of mixed grain preceded by a
      3.5-s delay). However, when the smaller-sooner and larger-later reinforcers were
      contingent on a concurrent fixed-ratio 31 schedule (the first 30 pecks
      distributed in any way on the two keys), all pigeons obtained the larger-later
      reinforcer much more often than they did when only a single peck was required.
      This "self-control" was achieved by beginning to peck the key leading to the
      larger-later reinforcer and persisting on that key until reinforcement occurred.
      We call this persistence "soft commitment" to distinguish it from strict
      commitment, in which self-control is achieved by preventing changeovers. Soft
      commitment also effectively achieved self-control when a brief (1-s) signal was
      inserted between the 30th and 31st response of the ratio and with concurrent
      fixed-interval 30-s schedules (rather than ratio schedules) of reinforcement. In
      a second experiment with the same subjects, the fixed ratio was interrupted by
      darkening both keys and lighting a third (center) key on which pecking was
      required for various fractions of the fixed-ratio count. The interruption
      significantly reduced self-control. When interruption was complete (30 responses
      on the center key followed by a single choice response), pigeons chose the
      smaller-sooner reinforcer as frequently as they did when only a single choice
      response was required.

PMID- 7561672
TI  - The effects of different tasks on the comprehension and production of idioms in
      children.
AB  - The present study investigated the developmental processes which lead from a
      literal interpretation of idiomatic expression to the ability of comprehending
      and producing them figuratively. A Model of the Development of Figurative
      Competence was presented according to which acquisition of idioms occurs as part
      of the general process of language and world knowledge development. Three
      experiments were carried out with second- and fourth-grade children, in which
      comprehension tasks - Recall, Multiple Choice, Paraphrase - and a production task
      - Completion - were employed. The results showed that younger children are more
      literally oriented than older children who in turn are more idiomatically
      oriented and that children of both age groups found it more difficult to produce
      idiomatic expressions than to comprehend them.

PMID- 7561673
TI  - Preschoolers' strategic behavior and performance on a same-different task.
AB  - Preschoolers' strategic behavior was examined on a task in which they must decide
      whether two arrays are the same. Fifty-six 3- and 4-year-olds selected doors to
      open which exposed parts of the arrays. Children made moderate use of an
      appropriate "vertical-pairs" strategy - viewing spatially corresponding parts of
      the two arrays - and it facilitated performance. Telling nonstrategic children to
      use the strategy or executing it for them improved their same-different
      judgments. However, increased spontaneous production of the vertical-pairs
      strategy over trials did not consistently improve judgments, which suggests a
      strategy utilization deficiency. Other microgenetic analyses revealed that
      children tended to use several strategies over the trials and that strategy
      changes often were not developmentally progressive or driven by failure of
      another strategy. The discussion addressed production and utilization
      deficiencies and the diversity of strategy development.

PMID- 7561674
TI  - Expression of HLA-C molecules confers target cell resistance to some non-major
      histocompatibility complex-restricted T cells in a manner analogous to
      allospecific natural killer cells.
AB  - Specific HLA molecules have recently been shown to confer target cell resistance
      to lysis by some CD3- natural killer (NK) cells. For certain NK clones,
      resistance is governed by two specificities (NK1 and NK2) that are associated
      with particular HLA-C alleles: in general, target cells expressing Cw1, Cw3, Cw7,
      or Cw8 are susceptible to NK1 but resistant to NK2 clones, whereas target cells
      expressing Cw2, Cw4, Cw5, or Cw6 are susceptible to NK2 and resistant to NK1
      cells. These two clusters of HLA-C alleles are distinguished by a dimorphism in
      the alpha 1 helical region, localized at amino acid positions 77 and 80. In this
      report, we show that highly enriched CD3+/CD56- cytotoxic T cell sublines and CD3
      /CD56+ NK sublines derived from the same donor have identical cytolytic
      specificities when tested against a panel of allogeneic LCL and various HLA-B and
      -C transfectant cell lines. The lysis pattern of the allogeneic cells appeared to
      be related to the NK2 specificity for both effector cells: LCL expressing HLA
      Cw2, Cw4, Cw5, or Cw6 alleles were lysed, while LCL expressing HLA-Cw1, Cw3, or
      Cw7 molecules were resistant. Resistance to lysis could be conferred to
      susceptible target cells by transfection with a Cw*0702 gene, while expression of
      a Cw*0602 gene did not provide protection. Similar patterns of HLA-C-mediated
      resistance were also found with two polyclonal T cell lines generated from the
      peripheral blood lymphocytes of unrelated donors. Thus, major histocompatibility
      complex (MHC) molecules that induced resistance to particular NK cells also
      regulated target cell resistance to lysis by these non-MHC-restricted effector T
      cells. For both types of effector cells, direct binding to HLA-C molecules was
      necessary to achieve inhibition since preincubation with mAb specific for class I
      molecules destroyed the protection from lysis of HLA-Cw7 expressing target cells.
      mAbs specific for CD3 and CD8 molecules had no influence on lysis or inhibition
      of the NK-like T cells. Formation of MHC complexes with particular peptides did
      not appear to be essential to confer resistance, since a cell line with defective
      peptide transporter genes (TAP genes), when transfected with an appropriate HLA-C
      allele, was as resistant to lysis as HLA-C transfectant lines with normal TAP
      function. These results suggest that HLA-C molecules may deliver negative
      regulatory signals to some non-MHC-restricted T cells in a manner similar to that
      described previously for particular NK cells.

PMID- 7561675
TI  - Multiple specificities in the repertoire of a melanoma patient's cytolytic T
      lymphocytes directed against tumor antigen MAGE-1.A1.
AB  - Peptide MAGE-1.A1 is a nonamer derived from protein MAGE-1 that can associate
      with the HLA-A1 molecule. It was shown previously to be recognized by an
      antitumor cytolytic T lymphocyte (CTL) clone derived from the blood of melanoma
      patient MZ2. We derived two other anti-MAGE-1.A1 CTL clones from different blood
      samples of the same patient and compared the fine specificity of recognition of
      the three CTL by testing them on variant MAGE-1.A1 peptides incorporating
      different amino acid substitutions. The epitopes recognized by the CTL proved to
      be different. While modifications of residues at positions 5, 6, or 7 in the
      antigenic peptide affected recognition by the three CTL, each of the
      modifications of residues at positions 1, 4, or 8 affected recognition by one CTL
      only. The sequences of both the alpha and beta chains of the T cell antigen
      receptor of the three CTL were completely different. The results indicate a long
      lasting diversity in terms of fine specificity and of T cell antigen receptor
      structure in the repertoire of antitumor CTL derived from the blood of a melanoma
      patient and directed against a defined tumor antigen.

PMID- 7561676
TI  - T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP
      70, and CD3 zeta despite suppressed cytolytic activity.
AB  - Loss of T cell-associated signal transduction molecules has recently been
      implicated in immune suppression in tumor-bearing hosts. In the present study, we
      have examined this and related phenomenon extensively in a large number of tumor
      bearing mice, analyzed individually. Splenic T cells from tumor-bearing mice were
      isolated and characterized with respect to the following: (a) levels of three
      tyrosine kinases, p56lck, p59fyn, and ZAP-70; (b) expression of CD3-zeta; (c)
      alloreactive responses; and (d) antigen-specific responses. Contrary to recent
      reports, T cells from tumor-bearing mice were observed to express normal levels
      of lck, fyn, ZAP-70, and CD3-zeta. Further, T cells showed healthy alloreactive
      and antigen-specific responses until approximately 3 wk after post tumor
      challenge, when the tumors constituted approximately 20% of the body weight.
      Alterations with respect to some parameters were observed only in mice that had
      been bearing larger tumors for a considerably longer period. As human tumors are
      unlikely to grow to such large sizes (e.g., > 20% of the total body weight), the
      significance of the alterations in T cell expression of lck, fyn, ZAP-70, or CD3
      zeta in the immune status of cancer patients is unclear. Altogether, these
      results indicate that alterations in T cell signal transduction molecules do not
      account for the profound tumor-specific suppression observed during tumor growth.

PMID- 7561677
TI  - Penetration of the blood-brain barrier: enhancement of drug delivery and imaging
      by bacterial glycopeptides.
AB  - The blood-brain barrier restricts the passage of many pharmacological agents into
      the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier
      permeability when they are present in the subarachnoid space during meningitis.
      By presenting such glycopeptides intravenously, blood-brain barrier permeability
      in rabbits was enhanced in a reversible time- and dose-dependent manner to agents
      < or = 20 kD in size. Therapeutic application of this bioactivity was evident as
      enhanced penetration of the antibiotic penicillin and the magnetic resonance
      imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the
      brain parenchyma.

PMID- 7561679
TI  - Absence of ZAP-70 prevents signaling through the antigen receptor on peripheral
      blood T cells but not on thymocytes.
AB  - Recently, a severe combined immunodeficiency syndrome with a deficiency of CD8+
      peripheral T cells and a TCR signal transduction defect in peripheral CD4+ T
      cells was associated with mutations in ZAP-70. Since TCR signaling is required in
      developmental decisions resulting in mature CD4 (and CD8) T cells, the presence
      of peripheral CD4+ T cells expressing TCRs incapable of signaling in these
      patients is paradoxical. Here, we show that the TCRs on thymocytes, but not
      peripheral T cells, from a ZAP-70-deficient patient are capable of signaling.
      Moreover, the TCR on a thymocyte line derived from this patient can signal, and
      the homologous kinase Syk is present at high levels and is tyrosine
      phosphorylated after TCR stimulation. Thus, Syk may compensate for the loss of
      ZAP-70 and account for the thymic selection of at least a subset of T cells
      (CD4+) in ZAP-70-deficient patients.

PMID- 7561678
TI  - Requirement for natural killer cell-produced interferon gamma in defense against
      murine cytomegalovirus infection and enhancement of this defense pathway by
      interleukin 12 administration.
AB  - The presence of natural killer (NK) cells contributes to early defense against
      murine cytomegalovirus (MCMV) infection. Although NK cells can mediate in vivo
      protection against MCMV, the mechanism by which they do so has not been defined.
      The studies presented here evaluate cytokine production by NK cells activated
      during MCMV infection and the role of NK cell-produced cytokines in early in vivo
      antiviral defenses. Experiments with normal C57BL/6, T cell-deficient C57BL/6
      nude, and severe combined immunodeficient mice lacking T and B cells demonstrated
      that both interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) production
      were induced at early times after infection with MCMV. Conditioned media samples
      prepared with cells from these mice, on day 2 after infection, produced 11-43
      pg/million cells of IFN-gamma and 12-19 pg/million cells of TNF as evaluated by
      specific protein enzyme-linked immunosorbent assays. Studies in the NK- and T
      cell-deficient mouse line, E26, in mice that had been depleted in vivo of NK
      cells by treatment with antibodies eliminating NK cells, anti-asialo ganglio-N
      tetraosylceramide or anti-NK1.1, and with populations of cells that had been
      depleted of NK cells by complement treatment with the anti-NK cell antibody,
      SW3A4, demonstrated that NK cells were solely responsible for the IFN-gamma but
      were not required for TNF production. The in vivo absence of NK cells was
      accompanied by increased viral hepatitis and viral replication in both
      immunocompetent and immunodeficient mice, as well as decreased survival time of
      immunodeficient mice. In vivo treatments with antibodies neutralizing IFN-gamma
      demonstrated that this factor contributed to the NK cell-mediated antiviral
      defense and reduced the measured parameters of viral defense to levels
      indistinguishable from those observed in NK cell-deficient mice. These effects
      appeared to be independent of cytolytic activity, as NK cells isolated from anti
      IFN-gamma-treated mice mediated killing at levels comparable to those observed in
      control-treated mice. The consequences of interleukin 12 (IL-12) administration,
      a known potent inducer of IFN-gamma production by NK cells, were evaluated in
      MCMV-infected mice. Low IL-12 doses, i.e., 1 ng/d, increased NK cell cytotoxicity
      and IFN-gamma production up to twofold and resulted in improved antiviral status;
      virus-induced hepatitis was decreased as much as fivefold, and viral burdens were
      decreased to levels below detection.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7561680
TI  - Cytokine interactions in human immunodeficiency virus-infected individuals: roles
      of interleukin (IL)-2, IL-12, and IL-15.
AB  - Cytokines have been shown to be powerful regulators of the immune response. In
      this study, we analyze the effect that the newly recognized cytokine interleukin
      (IL)-15 has on proliferation and cytokine induction using peripheral blood
      mononuclear cells (PBMCs) and purified CD4+ T cells from patients infected with
      human immunodeficiency virus (HIV) who are at various stages in their disease. We
      observed that IL-15 enhances the proliferative response in a dose-dependent
      manner from PBMCs of HIV-infected individuals when stimulated by polyclonal
      mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15
      are substantially diminished by adding a neutralizing antibody to the beta chain
      of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is
      enhanced by the presence of endogenous IL-2 produced in the cultures. The effect
      that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from
      PBMC's or CD4+ T cells in response to mitogen or tetanus toxoid was also
      examined. This was compared to the effect that exogenous IL-2 and IL-12 had under
      the same conditions. Addition of IL-2 or IL-15 to short-term in vitro cultures of
      either PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma
      production. By contrast, IL-12 caused substantial enhancement of both IL-2 and
      IFN-gamma production from these cultures. The role that endogenous cytokines have
      on IFN-gamma induction was also studied. Addition of a neutralizing antibody to
      the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures
      caused a striking decrease in IFN-gamma production. Neutralization of endogenous
      IL-15 also resulted in diminished IFN-gamma production from cultures stimulated
      with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4+ T cells
      stimulated with mitogen was assessed to see if we could detect a specific bias of
      cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but
      not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also
      produced from these same cultures. These results further elucidate the mechanism
      of cytokine regulation in HIV-infected individuals, and they provide evidence
      that IL-15 may be a useful immune modulator.

PMID- 7561681
TI  - Human intestinal epithelial cell-induced CD8+ T cell activation is mediated
      through CD8 and the activation of CD8-associated p56lck.
AB  - The activation of CD8+ suppressor T cells by normal intestinal epithelial cells
      in antigen-specific or allogeneic mixed cell culture systems has significant
      implications for the regulation of mucosal immune responses. In this study, we
      found that the capacity of epithelial cells to induce CD8+ suppressor T cell
      activation appeared to be linked to the binding of CD8 molecules on the T cell
      surface. This appears to be mediated by a non-class I molecule expressed on the
      epithelial cell surface, which binds to CD8 and results in the activation of the
      CD8-associated src-like tyrosine kinase, p56lck. Epithelial cell-stimulated
      p56lck activation is an early event (in contrast to monocytes) and is essential
      for T cell activation, since proliferation could be completely abrogated by
      pretreatment of T cells with genestein or herbamycin, both of which are protein
      tyrosine kinase inhibitors. Pretreatment of T cells with anti-CD8 or of
      intestinal epithelial cells with an anti-epithelial cell mAb B9 inhibited p56lck
      activation and further confirmed that CD8 on the T cell and a CD8 ligand on the
      epithelial cell were involved in this T cell activation event. The specificity of
      this reaction was confirmed in experiments in which murine transfectants 3G4 and
      3G8, expressing CD4 or CD8, respectively, were used. Coculture of 3G8 with
      epithelial cells but not with monocytes activated p56lck in this cell line,
      whereas p56lck was preferentially activated in 3G4 cells when monocytes were used
      as the stimulator cells. Although stimulation through CD8- and CD8-associated
      p56lck was important for epithelial cell-induced T cell activation, T cell
      proliferation could not be induced by cross-linking CD8 alone with monoclonal
      antibody anti-CD8. These data suggest that a second signal, possibly through the
      T cell antigen receptor since activation of the T cell receptor-associated kinase
      fyn was also seen, is required for epithelial cell-driven T cell proliferation.

PMID- 7561682
TI  - Direct association of pp125FAK with paxillin, the focal adhesion-targeting
      mechanism of pp125FAK.
AB  - Focal adhesion kinase (pp125FAK) is localized to focal adhesions and tyrosine
      phosphorylated by the engagement of beta 1 integrins. However, it is unclear how
      pp125FAK is linked to integrin molecules. We demonstrate that pp125FAK is
      directly associated with paxillin, a 68-kD cytoskeleton protein. The COOH
      terminal domain of pp125FAK spanning FAK residues 919-1042 is sufficient for
      paxillin binding and has vinculin-homologous amino acids, which are essential for
      paxillin binding. Microinjection and subsequent immunohistochemical analysis
      reveal that glutathione S-transferase-FAK fusion proteins, which bind to
      paxillin, localize to focal adhesions, whereas fusion proteins with no paxillin
      binding activity do not localize to focal adhesions. These findings strongly
      suggest that pp125FAK is localized to focal adhesions by the direct association
      with paxillin.

PMID- 7561683
TI  - T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl
      2-deficient mice.
AB  - Bcl-2 expression is tightly regulated during lymphocyte development. Mature
      lymphocytes in Bcl-2-deficient mice show accelerated spontaneous apoptosis in
      vivo and in vitro. Stimulation of Bcl-2-deficient lymphocytes by anti-CD3
      antibody inhibited the spontaneous apoptosis not only in T cells but also in B
      cells. The rescue of B cells was dependent on the presence of T cells, mainly
      through CD40L and interleukin (IL)-4. Furthermore, we generated Bcl-2-deficient
      mice transgenic for a T cell receptor or an immunoglobulin, both specific for
      chicken ovalbumin, to test for antigen-specific T-B cell interaction in the
      inhibition of the spontaneous apoptosis. The initial T cell activation by
      antigenic peptides presented by B cells suppressed apoptosis in T cells.
      Subsequently, T cells expressed CD40L and released ILs, leading to the protection
      of B cells from spontaneous apoptosis. These results suggest that the
      antiapoptotic signaling via CD40 or IL-4 may be largely independent of Bcl-2.
      Engagement of the Ig alone was not sufficient for the inhibition of B cell
      apoptosis. Thus, the physiological role of Bcl-2 in mature lymphocytes may be to
      protect cells from spontaneous apoptosis and to extend their lifespans to
      increase the opportunity for T cells and B cells to interact with each other and
      specific antigens in secondary lymphoid tissues. Bcl-2, however, appears to be
      dispensable for survival once mature lymphocytes are activated by antigen
      specific T-B cell collaboration.

PMID- 7561684
TI  - Identification of dendritic cell colony-forming units among normal human CD34+
      bone marrow progenitors that are expanded by c-kit-ligand and yield pure
      dendritic cell colonies in the presence of granulocyte/macrophage colony
      stimulating factor and tumor necrosis factor alpha.
AB  - Several cytokines, especially granulocyte/macrophage colony-stimulating factor
      (GM-CSF) and tumor necrosis factor alpha (TNF-alpha), have been identified that
      foster the development of dendritic cells from blood and bone marrow precursors
      in suspension cultures. These precursors are reported to be infrequent or to
      yield small numbers of dendritic cells in colony-forming assays. Here we readily
      identify dendritic cell colony-forming units (CFU-DC) that give rise to pure
      dendritic cell colonies. Human CD34+ bone marrow progenitors were expanded in
      semi-solid cultures with serum-replete medium containing c-kit-ligand, GM-CSF,
      and TNF-alpha. The addition of TNF-alpha to GM-CSF did not alter the number of
      typical GM colonies but did generate pure dendritic cell colonies that accounted
      for approximately 40% of the total colony growth. When the two distinct types of
      colonies were plucked from methylcellulose and tested for T cell-stimulatory
      activity in the mixed leukocyte reaction, the potency of colony-derived dendritic
      cells exceeded that of CFU-GM progeny from the same cultures by at least 1.5-2
      logs. Immunophenotyping and cytochemical staining of the CFU-DC-derived progeny
      was also characteristic of dendritic cells. Other myeloid cells were not
      identified in these colonies. The addition of c-kit-ligand to GM-CSF- and TNF
      alpha-supplemented suspensions of CD34+ bone marrow cells expanded CFU-DCs almost
      100-fold by 14 d. We conclude that normal human CD34+ bone marrow cells include
      substantial numbers of clonogenic progenitors, distinct from CFU-GMs, that can
      give rise to pure dendritic cell colonies. These CFU-DCs can be expanded for
      several weeks by in vitro culture with c-kit-ligand, and their differentiation
      requires exogenous TNF-alpha in addition to GM-CSF. We speculate that this
      dendritic cell-committed pathway may in the steady state contribute cells to the
      epidermis and afferent lymph, where dendritic cells are the principal myeloid
      cell type, and may increase the numbers of these specialized antigen-presenting
      cells during T cell-mediated immune responses.

PMID- 7561685
TI  - Molecular and immunological characterization of hr44, a human ocular component
      immunologically cross-reactive with antigen Ov39 of Onchocerca volvulus.
AB  - Structural similarities between host self-antigens and infectious organisms may
      be involved in the expression of autoimmune reactivity and development of
      autoimmune disease. The unique eye pathology associated with Onchocerca volvulus
      infection, particularly the development of posterior segment lesions, may be
      promoted by such autoreactive responses. Ov39 is a parasite-derived antigen that
      has been shown previously to be antigenically cross-reactive with a 44,000-M(r)
      host ocular component. A clone, designated hr44, was isolated from a cDNA library
      of human retina by immunoscreen using serum to Ov39. A monoclonal antibody raised
      to Ov39 also reacted with hr44 and gave evidence for a shared conformational
      epitope. The primary structure analysis showed that identities between the
      antigens are limited and confined to small peptides. The cross-reactivity between
      the antigens appears to involve T cells, since Ov39-specific T cells can be
      stimulated by hr44, a neural-specific antigen. Based on secondary structure
      prediction, hr44 has the typical features of a membrane-associated type I antigen
      with an amino-terminal extracellular domain. mAbs and antisera localized the
      antigen in the optic nerve, neural retina, retinal pigment epithelium, as well as
      the epithelial layers of ciliary body and iris.

PMID- 7561688
TI  - Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2
      microglobulin: a model of human spondyloarthropathies.
AB  - Human class I major histocompatibility complex allele HLA-B27 is associated with
      a group of human diseases called "spondyloarthropathies." Studies on transgenic
      rats expressing HLA-B27 and human beta 2-microglobulin have confirmed the role of
      HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory
      arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin (B27+ beta 2m-/
      ). In the absence of beta 2-microglobulin, B27+ beta 2m-/- animals do not express
      the HLA-B27 transgene on the cell surface and have a very low level of CD8+ T
      cells. Most of the B27+ beta 2m-/- male mice showed nail changes, hair loss, and
      swelling in paws, which leads to ankylosis. The symptoms occur only after the
      B27+ beta 2m-/- mice are transferred from the specific pathogen-free mouse
      colony. These results suggest that aberrant assembly, transport, and expression
      of the HLA-B27 molecule may predispose an individual for development of the
      disease when exposed to an appropriate environmental trigger.

PMID- 7561687
TI  - Early embryo loss is associated with local production of nitric oxide by decidual
      mononuclear cells.
AB  - In early embryo loss, the fetus may be considered to be an allograft and,
      therefore, may be rejected by maternal immunocytes. However, the cytotoxic
      mechanisms involved are still poorly understood. We have previously shown the
      involvement of natural killer (NK) cells and mononuclear cells expressing Mac-1
      (CD11b) and F4/80 in resorbing compared to nonresorbing embryos. In this study,
      the role of nitric oxide (NO) in the mechanism of early embryo loss was studied.
      Pregnant CBA/J females mated with DBA/2 males (20-30% early embryo loss) and CD1
      females mated with CD1 males (5-10% early embryo loss) were studied on days 8,
      10, and 12 of gestation. Cells from the implantation sites of individual embryos
      were tested for the production of nitrite and nitrate with or without in vitro
      challenge with lipopolysaccharide (LPS) to determine whether decidual macrophages
      were primed in situ. On day 12 of gestation, when resorption was clearly visible,
      resorbing embryos showed more than a fivefold increase in both basal- and LPS
      induced nitrite and nitrate production compared to nonresorbing embryos in both
      mouse strains tested, indicating that the decidual mononuclear cells were primed.
      Furthermore, more than 20% of CBA/J embryos showed a significant nitrate release
      on days 8 and 10 of gestation before any signs of embryo cytopathology. This
      percentage corresponded to the spontaneous resorption rate seen in CBA/J female X
      DBA/2 male matings. Similarly, 4% of the embryos from pregnant CD1 mice on days 8
      and 12 of gestation produced a significant amount of nitrate, which again
      correlated with the low incidence of resorption observed in these mice. Using
      immunohistochemistry, the presence of inducible nitric oxide synthase (iNOS) was
      detected at implantation sites. Furthermore, decidual cells positive for both
      iNOS and the macrophage marker Mac-1 were demonstrated in implantation sites by
      double immunostaining. This strongly suggests that decidual macrophages could be
      the cellular source of NO production. Aminoguanidine, a selective inhibitor of
      the iNOS, inhibited the in vitro production of nitric oxide by cells isolated
      from individual implantation sites, and more strikingly, significantly reduced
      early embryo losses in CBA/J females mated by DBA/2 males when given orally or
      parenterally to the gravid females starting on day 6 of gestation. In addition,
      aminoguanidine-treated pregnant mice showed a significant increase in average
      litter size when the pregnancies were allowed to proceed to term.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7561686
TI  - De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during
      cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x)
      oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.
AB  - Acute organ transplant rejection is characterized by a heavy lymphocyte
      infiltration. We have previously shown that alterations in the graft endothelium
      lead to increased lymphocyte traffic into the graft. Here, we demonstrate that
      lymphocytes adhere to the endothelium of rejecting cardiac transplants, but not
      to the endothelium of syngeneic grafts or normal hearts analyzed with the in
      vitro Stamper-Woodruff binding assay. Concomitant with the enhanced lymphocyte
      adhesion, the cardiac endothelium begins to de novo express sialyl Lewis(a) and
      sialyl Lewis(x) (sLea and sLex) epitopes, which have been shown to be sequences
      of L-selectin counterreceptors. The endothelium of allografts, but not that of
      syngeneic grafts or normal controls, also reacted with the L-selectin
      immunoglobulin G fusion protein, giving further proof of inducible L-selectin
      counterreceptors. The lymphocyte adhesion to endothelium could be significantly
      decreased either by treating the lymphocytes with anti-L-selectin antibody HRL-1,
      or by treating the tissue sections with sialidase or anti-sLea or anti-sLex
      monoclonal antibodies. Finally, we synthetized enzymatically several members of
      the sLex family oligosaccharides and analyzed their ability to block lymphocyte
      adhesion to cardiac endothelium. The monovalent sLex (a tetramer), divalent sLex
      (a decamer), and tetravalent sLex (a 22-mer) could all significantly reduce
      lymphocyte binding, but the inhibition by the tetravalent sLex-construct was
      clearly superior to other members of the sLex family. The crucial control
      oligosaccharides, sialyl lactosamines lacking fucose but being otherwise similar
      to the members of sLex family, had no effect on lymphocyte binding.

PMID- 7561689
TI  - Autoantibodies from patients with primary biliary cirrhosis preferentially react
      with the amino-terminal domain of nuclear pore complex glycoprotein gp210.
AB  - Patients with primary biliary cirrhosis frequently develop autoantibodies
      directed to gp210, a major glycoprotein of the nuclear pore complex. This protein
      contains a large glycosylated cisternal domain, a single transmembrane segment,
      and a short cytoplasmic tail. It has been previously shown that autoantibodies
      from primary biliary cirrhosis patients exclusively react with the cytoplasmic
      tail. We demonstrate that autoantibodies against gp210 recognize at least two
      different epitopes. 4 out of 12 anti-gp210 positive sera reacted with the
      fragment consisting of the cytoplasmic tail, and 8 sera targeted a novel epitope
      located within the large glycosylated lumenal domain. Moreover, our data prove
      that carbohydrate moieties are an essential part of this novel epitope. We
      propose, therefore, that future screening assays should be performed with
      antigens possessing both epitopes to detect all sera with anti-gp210 specificity.

PMID- 7561690
TI  - Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen
      receptor in patients with systemic sclerosis.
AB  - A novel subset of T cells characterized by the expression of an invariant T cell
      antigen receptor (TCR) encoded by V alpha 24J alpha Q gene segments was
      investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction
      analysis demonstrated that the V alpha 24 TCR repertoire was selectively used in
      CD4-CD8- double-negative T cells both in patients and in healthy individuals,
      while almost all families of TCR V alpha were expressed in single-positive T cell
      fractions. The V alpha 24+ double-negative T cells were increased by
      approximately fivefold in patients. However, sequence analysis clearly showed
      significant differences in the V alpha 24 TCR repertoire dominating in patients
      and healthy donors. In healthy individuals, the invariant V alpha 24J alpha Q was
      expanded and comprised 20-50% of the total TCR-alpha, while their selective
      reduction was observed in SSc patients who also showed expansion of invariant V
      alpha 24 TCR other than V alpha 24J alpha Q. Analogous to murine invariant V
      alpha 14J alpha 281 TCR, these results suggest that T cells with invariant V
      alpha 24J alpha Q TCR would function as regulatory T cells, whereas T cells
      bearing other invariant V alpha 24 TCR in SSc patients could be autoaggressive T
      cells in nature.

PMID- 7561691
TI  - Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil
      accumulation in vivo.
AB  - Experiments were designed to study the effect of systemically administered IL-5
      on local eosinophil accumulation induced by the intradermal injection of the
      chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated
      a rapid and dramatic increase in the numbers of accumulating eosinophils induced
      by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of
      locally accumulating eosinophils correlated directly with a rapid increase in
      circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h
      after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells
      corresponded with a reduction in the number of displaceable eosinophils recovered
      after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses
      tested, did not induce significant eosinophil accumulation. We propose that these
      experiments simulate important early features of the tissue response to local
      allergen exposure in a sensitized individual, with eosinophil chemoattractant
      chemokines having an important local role in eosinophil recruitment from blood
      microvessels, and IL-5 facilitating this process by acting remotely as a hormone
      to stimulate the release into the circulation of a rapidly mobilizable pool of
      bone marrow eosinophils. This action of IL-5 would be complementary to the other
      established activities of IL-5 that operate over a longer time course.

PMID- 7561692
TI  - Connections between signal transduction components and cellular responses
      initiated by antigen receptor on B lymphocytes.

PMID- 7561693
TI  - Requirement of phospholipase C-gamma 2 activation in surface immunoglobulin M
      induced B cell apoptosis.
AB  - Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple
      cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved
      in the activation of phosphatidylinositol pathway. DT40 B cells underwent
      apoptotic cell death when activated through sIgM, a phenomenon that is related to
      elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM
      signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of
      sIgM on PLC-gamma 2-deficient cells evoked neither inositol 1,4,5-trisphosphate
      nor calcium mobilization. In PLC-gamma 2- or Syk-deficient DT40 cells, the
      induction of apoptosis was blocked, but was still observed in Lyn-deficient
      cells. Src homology 2 domains of PLC-gamma 2 were essential for both its
      activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC
      gamma 2 is mediated by Syk, these results indicate that activation of PLC-gamma 2
      through Syk is required for sIgM-induced apoptosis.

PMID- 7561694
TI  - Successful T cell priming in B cell-deficient mice.
AB  - B cells are an abundant population of lymphocytes that can efficiently capture,
      process, and present antigen for recognition by activated or memory T cells.
      Controversial experiments and arguments exist, however, as to whether B cells are
      or should be involved in the priming of virgin T cells in vivo. Using B cell
      deficient mice, we have studied the role of B cells as antigen-presenting cells
      in a wide variety of tests, including assays of T cell proliferation and cytokine
      production in responses to protein antigens, T cell killing to minor and major
      histocompatibility antigens, skin graft rejection, and the in vitro and in vivo
      responses to shistosome eggs. We found that B cells are not critical for either
      CD4 or CD8 T cell priming in any of these systems. This finding lends support to
      the notion that the priming of T cells is reserved for specialized cells such as
      dendritic cells and that antigen presentation by B cells serves distinct
      immunological functions.

PMID- 7561695
TI  - A major histocompatibility complex class II restriction for BioBreeding/Worcester
      diabetes-inducing T cells.
AB  - Inbred diabetes-prone (DP) BioBreeding/Worcester (BB/Wor) (RT1u) rats develop
      spontaneous autoimmune diabetes, which, like human insulin-dependent diabetes
      mellitus, is mediated by autoreactive T lymphocytes. Breeding studies have shown
      an absolute requirement for at least one copy of the major histocompatibility
      complex (MHC) RT1u haplotype for spontaneous diabetes expression. Concanavalin A
      activated spleen cells from acutely diabetic DP rats adoptively transfer diabetes
      only to recipients that express at least one RT1u haplotype. To investigate the
      basis for the MHC requirement in BB/Wor autoimmunity, diabetes-inducing T cell
      lines were derived from the spleens of acutely diabetic DP rats. Upon activation
      in vitro with islet cells, the T cell lines adoptively transfer insulitis and
      diabetes into young DP recipients and non-diabetes-prone RT1 congenic rat strains
      that are class IIu. Recipients that are RT1u at only the class I A or C locus,
      but not at the class II B/D loci, do not develop diabetes after T cell transfer.
      The adoptive transfer of diabetes by Concanavalin A-activated diabetic DP spleen
      cells also requires that donor and recipient share class II B/Du gene products.
      Furthermore, the adoptive transfer of diabetes into MHC class IIu congenic rats
      is independent of the class I haplotype; i.e., it occurs in the presence of class
      I Aa Cu or Au Ca gene products. BB/Wor T cells can be activated in vitro for the
      transfer of diabetes with islet cell antigens and class II-positive but not class
      IIu-negative antigen-presenting cells. The inductive phase of BB diabetes is
      therefore MHC class II restricted, and this appears to operate at the level of
      interaction between inducing T cells and class IIu antigen-presenting cells.
      These results may explain the well-documented, but not yet understood, MHC class
      II genetic contribution to insulin-dependent diabetes mellitus pathogenesis, and
      they may facilitate the development of protocols designed to prevent diabetes
      onset in susceptible individuals.

PMID- 7561696
TI  - Interleukin 4 and T helper type 2 cells are required for development of
      experimental onchocercal keratitis (river blindness).
AB  - Inflammation of the corneal stroma (stromal keratitis) is a serious complication
      of infection with the nematode parasite Onchocerca volvulus. Because stromal
      keratitis is believed to be immunologically mediated in humans, we used a murine
      model to examine the role of T cells and T helper cell cytokines in the
      immunopathogenesis of these eye lesions. BALB/c mice immunized subcutaneously and
      injected intrastromally with soluble O. volvulus antigens (OvAg) developed
      pronounced corneal opacification and neovascularization. The corneal stroma was
      edematous and contained numerous eosinophils and mononuclear cells. Stromal
      keratitis in immunized mice was determined to be T cell dependent based on the
      following observations: (a) T cell-deficient nude mice immunized and injected
      intrastromally with OvAg fail to develop corneal pathology; and (b) adoptive
      transfer of spleen cells from OvAg-immunized BALB/c mice to naive nude mice
      before intrastromal injection of OvAg results in development of keratitis. OvAg
      stimulated lymph node and spleen cell cytokine production was dependent on CD4
      cells and included interleukin (IL)-4 and IL-5, but not interferon gamma,
      indicating a predominant T helper type 2 cell-like response. Inflamed corneas
      from immunized BALB/c mice and from reconstituted nude mice had greatly elevated
      CD4 and IL-4 gene expression compared with interferon gamma. Mice in which the IL
      4 gene was disrupted failed to develop corneal disease, demonstrating that IL-4
      is essential in the immunopathogenesis of O. volvulus-mediated stromal keratitis.

PMID- 7561697
TI  - Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor
      necrosis factor alpha, and nitric oxide in glial cultures derived from fetal,
      neonatal, and adult human brain.
AB  - Although microglia are the only cells found to be productively infected in the
      central nervous system of acquired immunodeficiency disease syndrome (AIDS)
      patients, there is extensive white and gray matter disease nonetheless. This
      neuropathogenesis is believed to be due to indirect mechanisms other than
      infection with human immunodeficiency virus 1 (HIV-1). Cytokines and toxic small
      molecules have been implicated in the clinical and histopathological findings in
      CNS AIDS. Previously, we have demonstrated in rodent glial cultures the presence
      of biologically active epitopes of gp120 and gp41 that are capable of inducing
      interleukin 1 and tumor necrosis factor alpha. In this study, we map the HIV-1
      envelope epitopes that induce nitric oxide, inducible nitric oxide synthase,
      interleukin 1, and tumor necrosis factor alpha in human glial cultures. Epitopes
      in the carboxy terminus of gp120 and the amino terminus of gp41 induce these
      proinflammatory entities. In addition, we compare HIV-1 infection and pathology
      in glial cells derived from human brain taken at different states of maturation
      (fetal, neonatal, and adult brain) in an effort to address some of the clinical
      and histological differences seen in vivo. This study demonstrates that, in the
      absence of virus infection and even in the absence of distinct viral tropism,
      human glia respond like rodent glia to non-CD4-binding epitopes of gp120/gp41
      with cytokine and nitric oxide production. Differences among fetal, neonatal, and
      adult glial cells' infectivity and cytokine production indicate that, in addition
      to functional differences of glia at different stages of development, cofactors
      in vitro and in vivo may also be critical in facilitating the biological
      responses of these cells to HIV-1.

PMID- 7561698
TI  - Dual T cell receptor alpha chain T cells in autoimmunity.
AB  - Allelic exclusion at the T cell receptor alpha locus TCR-alpha is incomplete, as
      demonstrated by the presence of a number of T lymphocyte clones carrying two
      expressed alpha chain products. Such dual alpha chain T cells have been proposed
      to play a role in autoimmunity, for example, because of a second TCR-alpha beta
      pair having bypassed negative selection by virtue of low expression. We examined
      this hypothesis by generating mice of various autoimmunity-prone strains carrying
      a hemizygous targeted disruption of the TCR-alpha locus, therefore unable to
      produce dual alpha chain T cells. Normal mice have a low but significant
      proportion of T cells expressing two cell-surface TCR-alpha chains that could be
      enumerated by comparison to TCR-alpha hemizygotes, which have none.
      Susceptibility to various autoimmune diseases was analyzed in TCR-alpha
      hemizygotes that had been backcrossed to disease-prone strains for several
      generations. The incidence of experimental allergic encephalomyelitis and of
      lupus is not affected by the absence of dual TCR-alpha cells. In contrast,
      nonobese diabetic (NOD) TCR alpha hemizygotes are significantly protected from
      cyclophosphamide-accelerated insulitis and diabetes. Thus, dual alpha T cells may
      play an important role in some but not all autoimmune diseases. Furthermore,
      since protected and susceptible NOD mice both show strong spontaneous responses
      to glutamic acid decarboxylase, responses to this antigen, if necessary for
      diabetetogenesis, are not sufficient.

PMID- 7561699
TI  - Thymic selection and cell division.
AB  - Cell division during thymic selection was studied with a system in which purified
      populations of T cell antigen receptor (TCR)- CD4+8+ (double-positive [DP]) cells
      and fetal thymic epithelial cells (TEC) were reaggregated in tissue culture. In
      this system, immature DP cells differentiate into mature single-positive (SP)
      CD4+8- and CD4-8+ TCRhi cells within 3-4 d, indicative of positive selection. By
      adding the DNA precursor, bromodeoxyuridine, to the cultures and staining cells
      for bromodeoxyuridine incorporation, T cell division in reaggregation cultures
      was found to be high on day 1, low on day 2, and high on days 4-5. Cell
      separation studies established that cell division on day 1 was restricted to DP
      blast cells. In the absence of blast cells, small DP cells failed to proliferate
      and differentiated into SP cells without cell division, thus indicating that
      proliferation is not an essential component of positive selection. This applied
      to SP cells generated within the first 2-3 d. Surprisingly, the SP cells
      generated later in culture showed a high rate of cell division; the proliferating
      SP cells were TCRhi and included both CD4+8- and CD4-8+ cells. Turnover of TCRhi
      SP cells was also prominent in the normal neonatal thymus and in TEC
      reaggregation cultures prepared with adult lymph node T cells. We speculate that
      division of mature SP cells in the perinatal thymic microenvironment is driven by
      stimulatory cytokines released from TEC. Such proliferation could be a device to
      expand the mature T cell repertoire before export to the periphery.

PMID- 7561701
TI  - 52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced
      transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal
      and adult heart.
AB  - The 52-kD SS-A/Ro protein is one of the antigenic targets strongly associated
      with the autoimmune response in mothers whose children have manifestations of
      neonatal lupus. In addition to the cDNA clone we previously reported for the full
      length 52-kD SS-A/Ro protein, an interesting MOLT-4 cDNA clone, p52-2, was found
      to have an internal deletion of 231 nucleotides including the domain encoding the
      leucine zipper motif. To further investigate the nature of this deletion, genomic
      DNA clones were isolated from a lambda FIXII library. The complete gene for the
      full-length 52-kD protein (alpha form, 52 alpha) spans 10 kb of DNA and is
      composed of seven exons. Exon 1 contains only the 5' untranslated sequence, while
      the translation initiation codon is located 3 kb downstream in exon 2, which also
      encodes the three zinc finger motifs. Exon 4 encodes amino acids 168-245,
      including the coiled coil/leucine zipper domain. Exon 7 is the longest and
      encodes the rfp-like domain and the 3' untranslated region. The cDNA p52-2 can
      now be accounted for as a product of alternative messenger RNA (mRNA) derived
      from the splicing of exon 3 to exon 5, skipping exon 4, which results in a
      smaller protein (52 beta) with a predicted molecular weight of 45,000. An initial
      approach to identifying this alternatively spliced form in the human heart used a
      ribonuclease protection assay. Using an RNA probe corresponding to bases 674-964
      of the full-length cDNA, two protected mRNA fragments were identified, a 290-bp
      fragment corresponding to expression of 52 alpha and a smaller fragment of 144
      bp, the predicted size of 52 beta. Using reverse transcription followed by
      polymerase chain reaction, cDNAs from a 16-wk fetal heart, 24-wk heart, and adult
      heart were amplified with primers flanking exon 4. Two polymerase chain reaction
      products were observed in each tissue, one 1.0 kb likely representing 52 alpha
      and a second 0.78 kb, consistent with 52 beta. The 0.78-kb fragment identified in
      the 16-wk heart was cloned, and DNA sequencing confirmed the 52 beta type.
      Immunoprecipitation of in vitro-translated 35S-labeled 52 beta form was performed
      to evaluate the antigenicity of this novel form of 52-kD SS-A/Ro. 26 (87%) of 30
      sera tested from mothers whose children were known to have neonatal lupus
      immunoprecipitated the 52 beta form.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7561700
TI  - Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin
      7 and CD19 in B cell progenitors.
AB  - Bone marrow stromal cells promote B cell development involving recombinase gene
      directed rearrangement of the immunoglobulin genes. We observed that the stromal
      cell-derived cytokine interleukin 7 (IL-7) enhances the expression of CD19
      molecules on progenitor B-lineage cells in human bone marrow samples and
      downregulates the expression of terminal deoxynucleotidyl transferase (TdT) and
      the recombinase-activating genes RAG-1 and RAG-2. Initiation of the TdT
      downregulation on the first day of treatment, CD19 upregulation during the second
      day, and RAG-1 and RAG-2 downmodulation during the third day implied a cascade of
      IL-7 effects. While CD19 ligation by divalent antibodies had no direct effect on
      TdT or RAG gene expression, CD19 cross-linkage complete blocked the IL-7
      downregulation of RAG expression without affecting the earlier TdT response.
      These results suggest that signals generated through CD19 and the IL-7 receptor
      could modulate immunoglobulin gene rearrangement and repertoire diversification
      during the early stages of B cell differentiation.

PMID- 7561703
TI  - Physical exams.

PMID- 7561704
TI  - Compensating patients for adverse events.

PMID- 7561705
TI  - Mismedicating the elderly--says who?

PMID- 7561702
TI  - CD1-restricted CD4+ T cells in major histocompatibility complex class II
      deficient mice.
AB  - Rather unexpectedly, major histocompatibility complex class II-deficient mice
      have a significant population of peripheral CD4+ T lymphocytes. We have
      investigated these cells at the population and clonal levels. CD4+ T lymphocytes
      from class II-deficient animals are thymically derived, appear early in ontogeny,
      exhibit the phenotype of resting memory cells, are potentially functional by
      several criteria, and have a diverse T cell receptor repertoire. They do not
      include substantially elevated numbers of NK1.1+ cells. Hybridomas derived after
      polyclonal stimulation of the CD4+ lymphocytes from class II-deficient animals
      include a subset with an unusual reactivity pattern, responding to splenocytes
      from many mouse strains including the strain of origin. Most members of this
      subset recognize the major histocompatibility complex class Ib molecule CD1;
      their heterogeneous reactivities and T cell receptor usage further suggest the
      involvement of peptides and/or highly variable posttranslational modifications.

PMID- 7561706
TI  - Electrosurgical loop excision of the cervical transformation zone: the experience
      of family physicians.
AB  - BACKGROUND: Electrosurgical loop excision of the cervical transformation zone
      (ELECTZ) is an excisional surgical procedure for treatment of premalignant
      cervical disease and the abnormal transformation zone by wire loop electrodes.
      The purpose of this study was to describe and assess the clinical experiences and
      complications of family-physician-performed ELECTZ and ELECTZ conization.
      METHODS: Women who were scheduled for the ELECTZ or ELECTZ conization procedures
      were enrolled in the study between March 1992 and March 1993, inclusive. Subjects
      were recruited from the practices of six family physician colposcopists located
      at five sites. The ELECTZ and ELECTZ conization procedures were performed on
      patients with abnormal Papanicolaou (Pap) smears or abnormal histologic results
      and abnormal colposcopic findings. Procedural complications were documented.
      Subjects were serially assessed during the first postoperative year by Pap
      smears, colposcopy, and, when necessary, by biopsy to determine therapeutic cure.
      RESULTS: Of 198 subjects enrolled in the study, 148 women were assessed at least
      once in follow-up by Pap smear and colposcopy. Only 7.6% of women were defined as
      treatment failures by subsequent histologic assessment. Women treated by ELECTZ
      conization were older (32.2 vs 25.1 years, P = .02), were more likely to develop
      posttreatment cervical stenosis (25.9% vs 3.8%, P = .001), and were more likely
      to have the postoperative squamocolumnar junction positioned in the endocervical
      canal (32.4% vs 8.7%, P = .002) than were women treated by ELECTZ: Loop excision
      specimen margins demonstrated dysplasia for 27 (13.6%) subjects. Significant
      operative bleeding (> 25 mL) was noted in 6.8% of subjects. Histologic thermal
      artifact was reported for 9.6% of specimens. One case of microinvasive cancer and
      one case of invasive cancer were identified unexpectedly by ELECTZ conization.
      CONCLUSIONS: Electrosurgical loop excision of the cervical transformation zone
      and ELECTZ conization may be safely and effectively performed in office settings
      by family physicians. Complications and treatment failure rates for the ELECTZ
      and ELECTZ conization procedures were similar to those experienced by other
      clinicians.

PMID- 7561707
TI  - Treatment of Chlamydia pneumoniae infection in adult asthma: a before-after
      trial.
AB  - BACKGROUND: Some diseases previously believed to be noninfectious, eg, peptic
      ulcer disease, are now known to be caused by chronic infection. Recently, chronic
      Chlamydia pneumoniae infection has been suggested as a cause for adult-onset
      asthma. The purpose of this study was to determine whether antichlamydial
      treatment would affect the natural history of this disease. METHODS: An open
      label, before-after treatment trial was performed in a community-based, primary
      care office. Forty-six patients (mean age 47.7 years; range 17 to 78) with
      moderate to moderately severe, stable, chronic asthma were treated a median of 4
      weeks (range 3 to 9) with oral doxycycline (100 mg twice daily), azithromycin
      (1000 mg once weekly), or erythromycin (1000 mg daily). Post-treatment pulmonary
      function and asthma symptoms were compared with baseline values. Follow-up was an
      average of 6 months (range 1.5 to 36) post-treatment. RESULTS: Four patients with
      C pneumoniae respiratory tract infection developed chronic asthma, which
      disappeared after treatment in each case. Of the remaining 42 seroreactive
      patients who were treated a mean of 6 years after the development of chronic
      asthma, one half had either complete remission or major clinical improvement (3
      and 18 patients, respectively). This improvement was significantly more likely to
      occur in patients with early disease (P = .01) and before the development of
      fixed obstruction (P < .01). CONCLUSIONS: Antimicrobial therapy appeared to
      "cure" or significantly improve asthma in approximately one half of treated
      adults, and the response pattern was consistent with chlamydial pathogenesis. C
      pneumoniae infection in asthma may be clinically important and should be
      investigated further.

PMID- 7561708
TI  - Radiologic interpretation by family physicians in an office practice setting.
AB  - BACKGROUND: Radiology is an integral part of the office practice of many family
      physicians. Nevertheless, data are sparse on the performance of family physicians
      in this endeavor. This study investigated the performance of family physicians at
      interpreting radiographs ordered in a free-standing family practice office.
      METHODS: A consecutive series of radiographic studies performed at a family
      practice office during a 3-year period was surveyed. All radiographic studies
      included in this analysis (N = 1674) were separately interpreted by the family
      physician ordering the study and an overreading radiologist. If the
      interpretations agreed, the studies were accepted as having been correctly
      interpreted. Cases in which the interpretations disagreed were reexamined.
      RESULTS: Family physicians correctly interpreted 92.4% of the radiographic
      studies (95% confidence interval, 91.0 to 93.6). Their accuracy with extremity
      films (96.0%) was significantly higher than their accuracy with chest films
      (89.3%, P < .001). Family physicians were more likely to correctly interpret
      normal films (95.2%) than abnormal ones (85.9%, P < .001). Thirty-five percent of
      the cases in which there were differences between family physician and
      radiologist interpretations were correctly interpreted by family physicians.
      CONCLUSIONS: Family physicians showed a high degree of accuracy in radiologic
      interpretation in an office setting. Chest films were inherently more difficult
      to interpret than extremity films. Because correct interpretation depends on body
      part examined and the prevalence of disease, the performance of family physicians
      will probably vary in different practice settings.

PMID- 7561709
TI  - Identification of obesity: waistlines or weight? Nutrition, Exercise, and Obesity
      Research Group.
AB  - BACKGROUND: Obesity can be divided into "general" and "central." Since abnormal
      glucose and lipid metabolism are more strongly associated with central obesity,
      it may not be adequate to use a general measure, such as a weight-for-height
      index, to assess for obesity. An index of central obesity, such as the waist-to
      hip ratio, might be more appropriate. METHODS: Nurses measured height and weight
      for the body mass index (BMI = kilograms of mass divided by the square of the
      height in meters) and girths for the waist-to-hip ratio (WHR) in 414 patients
      aged 45 years and over. Patients completed an obesity-related questionnaire.
      RESULTS: Fifty-seven percent of patients had an elevated BMI. Fifty percent of
      men (95% confidence interval [CI], 46 to 55) and 78% of women (95% CI, 75 to 80)
      had central obesity based on elevated WHRs. Using an elevated WHR as the standard
      for central obesity, elevated WHR as the standard for central obesity, elevated
      BMI had a positive predictive value of only 64% and a negative predictive value
      of 68% in men. For women, the corresponding positive and negative predictive
      values were 84% and 31%, respectively. CONCLUSIONS: The data indicate that the
      practice of using only scales to identify "overweight" patients should be
      reevaluated since doing so will miss patients at risk. In primary care patients,
      particularly those 50 years of age and over, weight-for-height indices such as
      the BMI result in underdiagnosis of central obesity.

PMID- 7561710
TI  - Using a vaccine manager to enhance in-hospital vaccine administration.
AB  - BACKGROUND: Immunizations are effective and safe but underutilized. Inpatient
      hospitalizations offer an opportunity to update immunizations for both children
      and adults. METHODS: We tested two strategies for administering vaccines to
      hospitalized adults: a nurse practitioner vaccine manager, who assessed patient
      needs and administered vaccines without the attending physician's signature; and
      enhanced usual care, ie, need assessed by floor nurses and vaccines ordered by
      attending physicians. Evaluation was based on immunization rates during 2
      preintervention months compared with immunization rates during the 3-month
      intervention period, and on interviews with nurses and physicians regarding their
      evaluation of the acceptability of the two strategies. RESULTS: Three percent of
      patients needing a vaccine received it during hospitalization in the 2-month
      baseline period before our intervention. During the intervention period, 1252
      patients were admitted and available for assessment; 821 were assigned to the
      "enhanced usual-care" floors and 431 to the "vaccine-manager" floors. Of the
      patients receiving enhanced usual care, 54% had either inadequate or no
      assessment of vaccine need. Seventy-three percent of those who were properly
      assessed needed at least one vaccine, yet only 4% of those patients received a
      vaccine. All patients on the vaccine-manager floors were assessed; of these, 47%
      needed one or more vaccines. Thirty-four percent of patients needing a vaccine
      received it; however, 47% of patients needing a vaccine refused it. The family
      nurse practitioner spent an average of 15 minutes per patient in providing this
      service. Qualitative interviews with staff nurses and physicians demonstrated
      support for a separate vaccine manager program to immunize patients. CONCLUSIONS:
      A specially dedicated vaccine manager can be more effective in assessing the need
      for and in delivering vaccines than can attending physicians working with floor
      nurses. Using a vaccine manager, these tasks also can be accomplished in a
      reasonable time. Hospital staff regard this approach as acceptable.

PMID- 7561711
TI  - Neonatal circumcision: associated factors and length of hospital stay.
AB  - BACKGROUND: Controversy exists regarding the efficacy of routine neonatal
      circumcision of male infants. Little is known about parental or provider
      characteristics or the use of medical resources associated with this procedure.
      METHODS: Records of 3703 male infants born during 1990 and 1991 at four US sites
      were analyzed to discern associations between circumcision and the above factors.
      Analyses were limited to healthy infants. RESULTS: Eighty-five percent of the
      infants in the study population were circumcised. White and African-American male
      infants were much more likely to be circumcised than those of other races (odds
      ratios [ORs], 7.3 and 7.1, respectively, P < .001). Compared with self-pay
      patients, those covered by private insurance were 2.5 times more likely to be
      circumcised (P < .001). Logistic regression showed that rates for obstetricians
      and family physicians were not significantly different. Increased odds of
      circumcision were found if the mother received an episiotomy (OR = 1.9, P < .001)
      or cesarean section (OR = 2.1, P < .001). Circumcised infants stayed in the
      hospital an average of one fourth of a day longer than did those who were not
      circumcised (mean difference, 0.26 days; 95% confidence interval, 0.16 to 0.36).
      CONCLUSIONS: Mother's insurance status and race as well as surgical interventions
      during delivery are related to circumcision. Associations with episiotomy and
      cesarean section suggest physician and/or parental preference for interventional
      approaches to health care. Generalizing the difference in hospital length of stay
      to the United States suggests an annual cost between $234 million and $527
      million beyond charges for the procedure itself.

PMID- 7561712
TI  - Genetic and congenital defect conditions that mimic child abuse.
AB  - Several medical conditions have been reported to mimic the physical
      manifestations of child abuse and neglect (CAN). These conditions include
      genetic, congenital, and other disorders that may result in poor weight gain,
      bone fracture, or skin lesions that appear to be bruises or burns. Society
      demands that medical personnel who care for children be aware of the many
      indicators that suggest CAN. This article is a review of 6 of 18 cases among 264
      that were referred to a child abuse team over a 3-year period because of
      suspected abuse in which medical disorders were initially and erroneously
      diagnosed as CAN. This report also suggests ways to support aggrieved parents who
      have been mistakenly reported to be child abusers.

PMID- 7561713
TI  - Hand-held computers for family physicians.
AB  - Hand-held computers such as the Apple Newton MessagePad, HP 200LX, Psion 3a, and
      Franklin DBS-2 are now powerful enough to be useful to family physicians in their
      care of patients. Each fits in a laboratory coat pocket, weighs a pound or less,
      costs less than $700, turns on instantly, and has excellent battery life. A wide
      variety of software, including computerized medical records, medical calculators,
      and medical references, is available.

PMID- 7561714
TI  - SOAP to SNOCAMP: improving the medical record format.
AB  - Not since the development of the SOAP note in the problem-oriented medical record
      has there been a significant need to alter the format of medical record
      documentation. With the intrusion of third-party audits, malpractice attorney
      subpoenas, medical guidelines, and reimbursement code criteria into the practice
      of medicine, there is a need to expand the traditional SOAP note. This article
      proposes a new acronym, "SNOCAMP," for medical record documentation. SNOCAMP
      retains the SOAP format, which includes subjective, objective, assessment, and
      plan of treatment, with the addition of nature of the presenting complaint,
      counseling, and medical decision-making. It is hoped that this new, more explicit
      format will prove successful in meeting the divergent needs of practicing
      physicians, the patients they serve, and the inquiring minds that look over their
      shoulders.

PMID- 7561715
TI  - Clonidine-induced bradycardia.
AB  - Clonidine is an alpha-adrenergic agent that is used in the treatment of
      hypertension. Bradycardia has been described as a common effect of clonidine
      poisoning, but has rarely been described as a side effect at commonly prescribed
      dosages. Bradyarrhythmias, as a side effect, may have several manifestations and
      may be symptomatic or asymptomatic. This report proposes mechanisms for clonidine
      induced bradycardia, describes persons at risk for this effect, and outlines
      treatments and preventive measures.

PMID- 7561716
TI  - Just a spoonful of sugar....

PMID- 7561717
TI  - Laboratory diagnosis of iron deficiency anemia.

PMID- 7561718
TI  - C pneumoniae in adult asthma.

PMID- 7561719
TI  - The curse.

PMID- 7561720
TI  - Manipulating melatonin in red deer (Cervus elaphus): differences in the response
      to food restriction and lactation on the timing of the breeding season and
      prolactin-dependent pelage changes.
AB  - In this study, we investigated the influence of food availability and lactation
      upon seasonality in red deer. This was examined by testing the hypothesis that
      advancing the timing of breeding and autumn moult using the hormone melatonin
      will be prevented when the food availability of lactating hinds is severely
      restricted. This hypothesis was rejected. Implanting 1 g of melatonin between
      June 22 and November 30 resulted in advances in the timing of the onset of
      ovarian activity and winter coat growth of 18 and 35 days, respectively. Whilst
      the onset of ovarian activity was unaffected by lactation and restricted food
      availability, these factors significantly delayed the winter coat growth by 20
      days. The date of onset of winter primary fibre growth was negatively correlated
      to plasma concentrations of the hormone prolactin in July. We suggest that
      seasonal changes in the growth of primary hair fibres are modified by two
      mechanisms: the increasing duration of melatonin secretion, as day lengths
      decline, which depresses prolactin secretion, and low nutrition, which elevates
      prolactin secretion in lactating deer. To conclude, we have demonstrated that the
      sensitivity of red deer to photoperiodic influences is preserved in lactating
      animals at low levels of nutrition, and that the timing of the onset of the
      breeding season and winter coat growth differ detectably in their sensitivity to
      nutrition and lactation.

PMID- 7561722
TI  - Effects of castration on antler growth in fallow deer (Dama dama L.).
AB  - Morphology and histological structure of antlers grown after castration
      (performed on March 25) were studied in six young fallow bucks. In the year after
      castration, antlerogenesis occurred during the species-specific time span, and
      the shape of the antlers, which remained permanently in velvet, was normal.
      During a cold period in December/January, the distal parts of the antlers
      suffered from frostbite and were subsequently detached. The process of
      sequestration was similar to that leading to normal antler casting. The
      sequestration sites were soon covered with skin, but (limited) regrowth of antler
      tissue from the stumps was not observed before late April/early May, i.e., the
      time of normal antler regeneration. Simultaneously, growth of knobby
      protuberances started on the surface of the antlers. Histological analysis of
      biopsies taken on December 20 in the year after castration revealed that the
      central parts of the antlers consisted of cancellous lamellar bone with mainly
      secondary osteons. Peripheral to this, the bone tissue (forming the
      protuberances) was of a more immature nature and exhibited larger intertrabecular
      spaces. The outermost layer consisted of woven bone formed by intramembranous
      ossification from the periosteum and was undergoing active growth and remodeling
      at the time of biopsy. Thus, bone formation at these sites occurred during a
      period when no antler growth is observed in normal fallow bucks. The velvet
      covering the bony protuberances was of normal appearance.

PMID- 7561721
TI  - Effects of space flight on Xenopus laevis larval development.
AB  - Fifty-three fertilized Xenopus laevis embryos at early tail bud stage were
      launched into orbit aboard a Biocosmos satellite and remained in microgravity for
      11.5 days. During this period, the embryos hatched and continued to develop as
      free-living larvae. Forty-eight individuals survived the mission. Upon recovery
      these tadpoles had smaller heads/bodies and proportionately longer tails than
      ground controls. Almost all the flight animals had caudal lordosis and
      consequently swam in backward somersaults. Compared to ground-based controls,
      their notochords were significantly larger in cross-sectional area and were
      deformed. Caudal muscle fibers were less dense and involuted in a fashion
      indicative of degeneration. In contrast, cranial muscles associated with buccal
      pumping did not differ between the flight and control animals. Upon landing, the
      flight larvae were found to be negatively buoyant and lay on the bottom when they
      were not swimming. They had significantly smaller lungs than controls, suggesting
      that they had failed to inflate their lungs in microgravity. Additionally, the
      branchial baskets, gill filters and thymuses all showed signs of retarded
      development or degeneration. The caudal deformity that we observed in the flight
      X. laevis has been independently observed in three other space flight experiments
      where embryos were launched then hatched in space. In contrast, Xenopus larvae
      from another orbital experiment that were raised from fertilization through
      hatching in space did not exhibit any caudal abnormalities. These divergent
      results suggest that either features of the launch itself (i.e., high
      acceleration and vibration) or an abrupt decrease in gravity during the tail bud
      stage detrimentally affects musculoskeletal development in anurans.

PMID- 7561723
TI  - Responses to chronic hypoxia in embryonic alligators.
AB  - To investigate developmental responses to chronic hypoxia, we incubated alligator
      eggs at 17% O2 and 21% O2 for the entire course of embryonic development and for
      5 months post-hatching. Hypoxic-incubated alligators hatched later and at a
      smaller size. Hematocrit was significantly higher in hypoxic-incubated animals
      immediately post-hatch. Allosteric modification of hemoglobin oxygen affinity did
      not appear to play a role in the adaptation to hypoxia, given equal nucleotide
      triphosphate-to-hemoglobin ratios in the hypoxic and normoxic groups. When
      acutely exposed to 21% O2, hypoxic-incubated alligators maintained oxygen
      consumption relative to their normoxic siblings despite their lower mass.

PMID- 7561724
TI  - Descriptive kinetics of the seminiferous epithelium cycle and genome size in the
      mole Talpa occidentalis (Insectivora).
AB  - The male germ cell cytodifferentiative process of the mole Talpa occidentalis is
      described. Cytochemical procedures were used 1) to follow acrosome formation and
      spermatid differentiation, dividing the seminiferous epithelium cycle into ten
      stages, each characterized by typical germ cell-to-cell associations, and
      recognizing 13 steps in spermatid differentiation; 2) to monitor, in situ,
      histones replacement by protamines at step 11 of the spermiogenic process. The
      seminiferous epithelium cycle of the mole has the basic histological features
      present in all mammals and appears rather similar to that of the common shrew
      (Sorex araneus), the only one so far known among Insectivora. The metabolism of
      the DNA-associated proteins reveals that protamines replace histones during the
      late steps (11-13) of spermiogenesis, mRNA for protamines having been synthesized
      at an earlier step (assuming that in the mole this occurs at the first
      spermiogenic steps, as in the house mouse). In addition the genome size (5.0 pg)
      and the AT/GC ratio (1.3) were evaluated.

PMID- 7561725
TI  - Vitellogenins of Oreochromis niloticus: identification, isolation, and
      biochemical and immunochemical characterization.
AB  - Two native forms of vitellogenin (EIP1 and EIP2) were identified in the plasma of
      Oreochromis niloticus. They were present in females and were estrogen-inducible
      in males. Both were phosphoglycolipoproteins and both immunoreacted with the
      antiserum raised against egg proteins. Two prominent bands (EIpp1 and EIpp2;
      corresponding to 185 and 120 kDa, respectively), observed on sodium dodecyl
      sulfate-polyacrylamide gels, were induced by estradiol treatment of males and
      immunoreacted with the antiserum against egg proteins. EIP1 and EIP2 were
      isolated by precipitation with Mg2+ ions and ethylenediamine tetraacetic acid,
      preparative polyacrylamide gel electrophoresis, and electroelution. During
      purification the fractions containing EIP1 and EIP2 also retained EIpp2 and
      EIpp1, respectively. Immunoblot analyses using affinity-purified antibodies
      against EIP1, EIP2, EIpp1, and EIpp2 confirmed that EIP1 and EIP2 were at least
      composed of EIpp2 and EIpp1, respectively. These results suggest that at least
      two immunochemically different proteins are induced and are secreted into the
      blood to serve as vitellogenin and to provide a source of nutrient for the
      developing embryo of Oreochromis niloticus.

PMID- 7561726
TI  - Inhibitory action of hypoxanthine on meiotic resumption of denuded pig follicular
      oocytes in vitro.
AB  - The present study was conducted to investigate the direct action of hypoxanthine,
      which has been reported to be present in pig follicular fluid, on spontaneous
      meiotic resumption of pig denuded oocytes in vitro. No oocytes, which were
      surrounded by a cumulus and some membrana granulosa cells directly adjacent to it
      from healthy antral follicles, underwent germinal vesicle breakdown (GVBD) when
      they were cultured in serum-supplemented 199 with or without 4 mM hypoxanthine.
      On the other hand, 81% of denuded oocytes prepared from such cumulus-oocyte
      granulosa cell complexes showed GVBD after 24 h of culture. Hypoxanthine
      inhibited significantly this spontaneous resumption of meiosis in denuded
      oocytes. The inhibitory action of hypoxanthine was dose dependent at
      concentrations of 1-6 mM and was reversible following subsequent culture of the
      oocytes in hypoxanthine-free medium. However, premature chromosome condensation
      was observed in oocytes cultured in hypoxanthine-supplemented medium, and the
      oocytes released from the influence of hypoxanthine completed GVBD and reached
      the second metaphase slightly faster than those freshly isolated from the
      follicle. These results suggest that hypoxanthine inhibits spontaneous meiotic
      resumption of pig oocytes in vitro. However, the inhibitory action of
      hypoxanthine does not prevent all events involved in GVBD from occurring.

PMID- 7561728
TI  - Calcium, sulfur, and zinc distribution in normal and arthritic articular equine
      cartilage: a synchrotron radiation-induced X-ray emission (SRIXE) study.
AB  - Calcium, sulfur, and zinc content in normal and arthritic equine cartilage have
      been studied by synchrotron radiation-induced X-ray emission (SRIXE). Ranging
      from the superficial to the columnar zone of the normal tissue, calcium and zinc
      concentrations are increasingly higher, whereas sulfur is at its highest
      concentration in the transitional zone. In the arthritic tissue, calcium
      concentration is at its maximum in the transitional zone, whereas zinc and sulfur
      distributions are relatively homogeneous. Sulfur concentration in arthritic
      cartilage is reduced to about one-third with respect to that in normal tissue.
      The possibility that zinc concentration reflects the distribution of the zinc
      containing enzyme alkaline phosphatase is presented.

PMID- 7561727
TI  - Intratesticular retention of sperm and premature decline in fertility in the
      domestic rooster, Gallus domesticus.
AB  - In domestic roosters, which were originally seasonal breeders and that are now
      kept under unnatural and unchanging conditions throughout the year, fertility
      peaks at 32 weeks of age (96%) but it subsequently declines rapidly to only 5% at
      110 weeks despite the fact that roosters can live for about 10 years. Roosters
      exhibiting this low-fertility syndrome have reduced levels of spermatozoa in the
      ejaculate. Concomitantly, however, superabundant but apparently normal
      spermatozoa are found attached to Sertoli cells and, in addition, the
      seminiferous epithelium fails to show evidence of the regression of atrophy that
      characterizes both aging non-seasonal breeders and true seasonal breeders during
      non-reproductive periods. This syndrome of premature low fertility appears to
      stem from impaired spermiation with resultant retention of spermatozoa by Sertoli
      cells. To examine this problem, we compared intratesticular incorporation of 3H
      thymidine between high-fertility (32-week-old) and low-fertility (82-week-old)
      roosters. Radioactivity associated with spermatozoa, 33 days post-injection, was
      almost 50% higher in the low-fertility roosters than in the high-fertility ones.
      By contrast, both groups showed similar characteristics with respect to a)
      intratesticular incorporation of 3H-thymidine, b) dynamics of spermatogenesis, c)
      intratesticular level of radioactivity just before the initiation of spermiation,
      and d) the duration of both spermatogenesis and the time required for sperm to
      pass through the genital tract. Our results confirm that intratesticular
      retention of sperm occurs in roosters with premature low-fertility syndrome and
      suggest new possibilities for the study of the complex relationship between
      Sertoli cells and spermatozoa and the effects of this relationship on fertility.

PMID- 7561729
TI  - Who are we? We are teachers.

PMID- 7561731
TI  - Factitious disorder presenting as bacteremia. Case report and literature review.
AB  - A factitious disorder is typically a chronic illness that can be frustrating for
      the clinical team because it often eludes early diagnosis. Case reports in the
      literature show that patients can simulate almost any illness or disease state
      with some resorting to injecting themselves with contaminated substances to
      produce infection. A case is reported of a patient with self-induced bacteremia
      who presented with multiple episodes of polymicrobial bloodstream infections. The
      various types of factitious disorders and a review of treatment options are
      discussed. The current criteria for factitious disorders in the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV) 4th edition are reviewed.

PMID- 7561730
TI  - The black paintings and the Vogt-Koyanagi-Harada syndrome.
AB  - Francisco Goya, the Spanish painter, suffered from a disease of uncertain
      etiology which affected his vision, hearing, and balance. The nature of his
      illness probably was a curious syndrome known today as Vogt-Koyanagi=Harada or
      uveomeningoencephalytic syndrome. This is an autoimmune disorder which involves
      the visual and cochlear pigment derived from the neural crest. The common finding
      in all cases described in the literature is bilateral uveitis. It is interesting
      to speculate how the period of Goya's artistic output known as the "Black
      Paintings" might have been created during the time he had the disease.

PMID- 7561732
TI  - Medicaid costs of live births from unintended pregnancies in Florida.
AB  - The Florida Pregnancy Risk Assessment Monitoring System (PRAMS) survey, a
      population-based, random sample mail-telephone query of new mothers of live-born
      infants, includes questions about pregnancy timing and wantedness, sources of
      payment for care, other related topics, mother's risk behaviors, satisfaction
      with prenatal care, and the newborn's health. There were 2,059 completed
      responses in 1993. Results are weighted for factors affecting response rates to
      reflect all births. An estimated 13.8% (95% confidence interval 11.7, 15.9) of
      all Florida babies in 1993 were unwanted at conception, and 20.3% (16.5, 24.1) of
      those whose deliveries were paid for by Medicaid were unwanted. The Medicaid
      program currently pays for the prenatal, intrapartum, delivery and infant health
      care of an estimated 16,000 pregnancies and newborns each year that were unwanted
      at conception. The total annual cost is estimated at $401 million, or over 8% of
      all 1992-93 Medicaid costs.

PMID- 7561733
TI  - The medical information superhighway.
AB  - Commercial and private use of the Internet has grown exponentially over the last
      few years. Its estimated size increases by more than 10% per month. Medical
      information and resources are now available to aid physicians in practice and in
      research. Users can utilize email to communicate with other medical professionals
      around the world. The newest and possibly most significant development on the
      Internet is the World Wide Web. Through it, physicians may access multimedia
      resources such as databases of medical information, recent news and research,
      atlases, and electronic journals using an intuitive graphics interface. Medically
      related software can be obtained from the vast archives on the Internet via the
      FTP function. As the Internet expands and becomes more ubiquitious, its uses will
      multiply and become an important mode of medical information dissemination and
      acquisition.

PMID- 7561734
TI  - AP-1 transcription factor complexes in CNS disorders and development.
AB  - Transcription factors are regulatory proteins that modify gene expression. Any
      cellular function requiring alterations in mRNA levels depends upon these
      factors. The CNS, AP-1 (activator protein-1; c-fos and fos-related antigens plus
      jun-related factors) and CREB (cAMP responsive element binding protein) families
      of transcription factors have been extensively studied. The DNA binding complex
      is composed of dimers formed between the AP-1 and CREB factors and binding
      specificity is dictated by which proteins comprise the complex. Whereas the AP-1
      factors are inducible, CREB and related proteins are constitutive and regulate
      gene transcription through phosphorylation. Due to seizure activity, many AP-1
      factors are induced, but rapidly return to basal levels. However, if neuronal
      death occurs, fos-related antigens of 35 kDa persist for an extended period and
      may be involved in regulating genes related to neuronal plasticity. Similar
      factors are expressed after chronic drug treatment indicating a role in drug
      tolerance. However, during early CNS development, elevated AP-1 DNA binding
      consisting of c-jun and CREB occurs in every brain region and is inversely
      related to the degree of maturation of a particular brain area. These
      transcription factors are important for gene regulation during CNS dysfunction
      and development and those present specify which genes are activated.

PMID- 7561735
TI  - Quality improvement in medicare.

PMID- 7561736
TI  - Medicaid reimbursement.

PMID- 7561738
TI  - "Will anyone take a sip".

PMID- 7561737
TI  - More comments regarding rheumatology issue.

PMID- 7561739
TI  - Effects of ionic strength on the regulation of Na/H exchange and K-Cl cotransport
      in dog red blood cells.
AB  - Dog red cell membranes contain two distinct volume-sensitive transporters:
      swelling-activated K-Cl cotransport and shrinkage-activated Na/H exchange. Cells
      were prepared with intracellular salt concentration and weight percentage of cell
      water (%cw) varied independently by transient permeabilization of the cell
      membrane to cations. The dependence of transporter-mediated Na and K influxes
      upon %cw and upon extracellular salt concentration (c(ext)) was measured in cells
      so prepared. It was found that the critical value of %cw at which transporters
      are activated, called the set point, is similar for the two transporters, and
      that the set points for the two transporters decrease similarly with increasing
      extracellular salt concentration. These findings suggest a common mechanism of
      regulation of these two transporters. Cellular Na, K, and Cl concentrations were
      measured as functions of %cw and c(ext). Using these data together with data from
      the literature for other solute concentrations, empirical expressions were
      developed to describe the dependence of the intracellular concentrations of all
      significant small molecule electrolytes, and therefore the intracellular ionic
      strength, upon %cw and c(ext). A mechanistic model for the dependence of the set
      point of an individual transporter upon intracellular ionic strength is proposed.
      According to this model, the set point represents a critical extent of
      association between the transporter and a postulated soluble regulatory protein,
      called regulator. Model functions are presented for the calculation of the
      thermodynamic activity of regulator, and hence extent of regulator-transporter
      association, as a function of total intracellular protein concentration (or %cw)
      and ionic strength. The experimentally observed dependence of set point %cw on
      c(ext) are simulated using these functions and the empirical expressions
      described above, together with reasonable but not uniquely determined values of
      model parameters.

PMID- 7561742
TI  - Regions of beta 2 and beta 4 responsible for differences between the steady state
      dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal
      nicotinic receptors.
AB  - We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits
      to locate the regions that contribute to differences between the acetylcholine
      (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4
      receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an
      EC50 for ACh approximately 20-fold less than the EC50 of the alpha 3 beta 4
      receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas
      the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the
      first 120 residues convert the EC50 for ACh from one wild-type value to the
      other. Exchanging just beta 2:104-120 for the corresponding region of beta 4
      shifts the EC50 of ACh dose-response relationship in the expected direction but
      does not completely convert the EC50 of the dose-response relationship from one
      wild-type value to the other. However, substitutions in the beta 2:104-120 region
      do account for the relative sensitivity of the alpha 3 beta 2 receptor to
      cytisine, tetramethylammonium, and ACh. The expression of beta 4-like (strong)
      cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively
      short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2
      like values. The results suggest that amino acids within the first 120 residues
      of beta 2 and the corresponding region of beta 4 contribute to an agonist binding
      site that bridges the alpha and beta subunits in neuronal nicotinic receptors.

PMID- 7561741
TI  - Cd2+ regulation of the hyperpolarization-activated current IAB in crayfish
      muscle.
AB  - The effects of Cd2+ on the hyperpolarization-activated K(+)-mediated current
      called IAB (Araque, A., and W. Buno. 1994. Journal of Neuroscience. 14:399-408.)
      were studied under two-electrode voltage-clamp in opener muscle fibers of the
      crayfish Procambarus clarkii. IAB was reversibly reduced by extracellular Cd2+ in
      a concentration-dependent manner, obeying the Hill equation with IC50 = 0.452 +/-
      0.045 mM and a Hill coefficient of 1 (determined from the maximal chord
      conductance of IAB). Cd2+ decreased the IAB conductance (GAB) and shifted its
      voltage dependence towards hyperpolarized potentials in a similar degree, without
      affecting the slope of the voltage dependence. The IAB activation time constant
      increased, whereas the IAB deactivation time constant was not modified by Cd2+.
      The IAB equilibrium potential (EAB) was unmodified by Cd2+, indicating that the
      selective permeability of IAB channels was not altered. IAB was unaffected by
      intracellular Cd2+. The Cd(2+)-regulation of IAB did not depend on [K+]o, and the
      effects of [K+]o on IAB were unchanged by Cd2+, indicating that Cd2+ did not
      compete with K+. Therefore, Cd2+ probably bound to a different site to that
      involved in the K+ permeability pathway. We conclude that Cd2+ affected the
      gating of IAB channels, interfering with their opening but not with their closing
      mechanism. The results can be explained by a kinetic model in which the binding
      of Cd2+ to the IAB channels would stabilize the gating apparatus at its resting
      position, increasing the energy barrier for the transition from the closed to the
      open channel states.

PMID- 7561740
TI  - Monovalent and divalent cation permeability and block of neuronal nicotinic
      receptor channels in rat parasympathetic ganglia.
AB  - Acetylcholine-evoked currents mediated by activation of nicotinic receptors in
      rat parasympathetic neurons were examined using whole-cell voltage clamp. The
      relative permeability of the neuronal nicotinic acetylcholine (nACh) receptor
      channel to monovalent and divalent inorganic and organic cations was determined
      from reversal potential measurements. The channel exhibited weak selectivity
      among the alkali metals with a selectivity sequence of Cs+ > K+ > Rb+ > Na+ >
      Li+, and permeability ratios relative to Na+ (Px/PNa) ranging from 1.27 to 0.75.
      The selectivity of the alkaline earths was also weak, with the sequence of Mg2+ >
      Sr2+ > Ba2+ > Ca2+, and relative permeabilities of 1.10 to 0.65. The relative
      Ca2+ permeability (PCa/PNa) of the neuronal nACh receptor channel is
      approximately fivefold higher than that of the motor endplate channel (Adams, D.
      J., T. M. Dwyer, and B. Hille. 1980. Journal of General Physiology. 75:493-510).
      The transition metal cation, Mn2+ was permeant (Px/PNa = 0.67), whereas Ni2+,
      Zn2+, and Cd2+ blocked ACh-evoked currents with half-maximal inhibition (IC50)
      occurring at approximately 500 microM, 5 microM and 1 mM, respectively. In
      contrast to the muscle endplate AChR channel, that at least 56 organic cations
      which are permeable to (Dwyer et al., 1980), the majority of organic cations
      tested were found to completely inhibit ACh-evoked currents in rat
      parasympathetic neurons. Concentration-response curves for guanidinium,
      ethylammonium, diethanolammonium and arginine inhibition of ACh-evoked currents
      yielded IC50's of approximately 2.5-6.0 mM. The organic cations, hydrazinium,
      methylammonium, ethanolammonium and Tris, were measureably permeant, and
      permeability ratios varied inversely with the molecular size of the cation.
      Modeling suggests that the pore has a minimum diameter of 7.6 A. Thus, there are
      substantial differences in ion permeation and block between the nACh receptor
      channels of mammalian parasympathetic neurons and amphibian skeletal muscle which
      represent functional consequences of differences in the primary structure of the
      subunits of the ACh receptor channel.

PMID- 7561744
TI  - Response dynamics and receptive-field organization of catfish ganglion cells.
AB  - Responses from catfish retinal ganglion cells were evoked by a spot or an annulus
      of light and were analyzed by a procedure identical to the one used previously to
      study catfish amacrine cells (Sakai H. M., and K.-I. Naka, 1992. Journal of
      Neurophysiology. 67:430-442.). In two-input white-noise experiments, a response
      evoked by simultaneous stimulation of the center and surround was decomposed into
      the components generated by the center and surround through a process of cross
      correlation. The center and surround responses were also decomposed into their
      linear and nonlinear components so that the response dynamics of the linear and
      nonlinear components could be measured. We found that the concentric organization
      of the receptive field was determined by linear components, i.e., the first-order
      kernels generated by the center and surround were of opposite polarity. Both the
      center and surround generated second-order kernels with similar signatures, i.e.,
      the second-order components formed a monotonic receptive field. The peak response
      time of the first- and second-order kernels from the surround was longer by
      approximately 20 ms than that of the center. Except for the DC potential present
      in the intracellular responses, almost identical first- and second-order kernels
      for the center and surround were obtained from both the intracellular response
      and spike discharges. Thus, information on concentric organization of a receptive
      field is translated into spike discharges with little loss of information. A
      train of spike discharges carries, simultaneously, at least four kinds of
      information: two linear and two nonlinear components, which originate in the
      receptive field center and the surround. A spike train is not a simple signaling
      device but is a carrier of complex and multiple signals. Victor, J. D., and R. M.
      Shapley (1979. Journal of General Physiology. 74:671-687.) discovered similarly
      that, in the cat retina, static second-order nonlinearity is encoded into spike
      trains. Results obtained in this study support the thesis that signals generated
      by the preganglionic cells are translated into spike discharges without major
      modification and that those signals can be recovered from the spike trains
      (Sakuranaga, M., Y. Ando, and K.-I. Naka. 1987. Journal of General Physiology.
      90:229-259.; Korenberg, M. J., H. M. Sakai, and K.-I. Naka. 1989. Journal of
      Neurophysiology. 61:1110-1120.). Current injection studies have shown that such
      signal transmission is possible (Sakai, H. M., and K.-I. Naka, 1988a. Journal of
      Neurophysiology. 60:1549-1567.; 1990. Journal of Neurophysiology. 63:105-119.).

PMID- 7561743
TI  - Voltage-gated and Ca(2+)-activated K+ channels in intact human T lymphocytes.
      Noninvasive measurements of membrane currents, membrane potential, and
      intracellular calcium.
AB  - Voltage-gated n-type K(V) and Ca(2+)-activated K+ [K(Ca)] channels were studied
      in cell-attached patches of activated human T lymphocytes. The single-channel
      conductance of the K(V) channel near the resting membrane potential (Vm) was 10
      pS with low K+ solution in the pipette, and 33 pS with high K+ solution in the
      pipette. With high K+ pipette solution, the channel showed inward rectification
      at positive potentials. K(V) channels in cell-attached patches of T lymphocytes
      inactivated more slowly than K(V) channels in the whole-cell configuration. In
      intact cells, steady state inactivation at the resting membrane potential was
      incomplete, and the threshold for activation was close to Vm. This indicates that
      the K(V) channel is active in the physiological Vm range. An accurate,
      quantitative measure for Vm was obtained from the reversal potential of the K(V)
      current evoked by ramp stimulation in cell-attached patches, with high K+
      solution in the pipette. This method yielded an average resting Vm for activated
      human T lymphocytes of -59 mV. Fluctuations in Vm were detected from changes in
      the reversal potential. Ionomycin activates K(Ca) channels and hyperpolarizes Vm
      to the Nernst potential for K+. Elevating intracellular Ca2+ concentration
      ([Ca2+]i) by ionomycin opened a 33-50-pS channel, identified kinetically as the
      CTX-sensitive IK-type K(Ca) channel. The Ca2+ sensitivity of the K(Ca) channel in
      intact cells was determined by measuring [Ca2+]i and the activity of single K(Ca)
      channels simultaneously. The threshold for activation was between 100 and 200 nM;
      half-maximal activation occurred at 450 nM. At concentrations > 1 microM, channel
      activity decreased. Stimulation of the T-cell receptor/CD3 complex using the
      mitogenic lectin, PHA, increased [Ca2+]i, and increased channel activity and
      current amplitude resulting from membrane hyperpolarization.

PMID- 7561745
TI  - Contrast gain control in the lower vertebrate retinas.
AB  - Control of contrast sensitivity was studied in two kinds of retina, that of the
      channel catfish and that of the kissing gourami. The former preparation is
      dominantly monochromatic and the latter is bichromatic. Various stimuli were
      used, namely a large field of light, a spot-annulus configuration and two
      overlapping stimuli of red and green. Recordings were made from horizontal,
      amacrine, and ganglion cells and the results were analyzed by means of Wiener's
      theory, in which the kernels are the contrast (incremental) sensitivity.
      Modulation responses from horizontal cells are linear, in that the waveform and
      amplitude of the first-order kernels are independent of the depth of modulation.
      In the N (sustained) amacrine and ganglion cells, contrast sensitivity was low
      for a large modulation input and was high for a small modulation input, providing
      an example of contrast gain control. In most of the cells, the contrast gain
      control did not affect the dynamics of the response because the waveform of the
      first-order kernels remained unchanged when the contrast sensitivity increased
      more than fivefold. The signature of the second-order kernels also remained
      unchanged over a wide range of modulation. The increase in the contrast
      sensitivity for the second-order component, as defined by the amplitude of the
      kernels, was much larger than for the first-order component. This observation
      suggests that the contrast gain control proceeded the generation of the second
      order nonlinearity. An analysis of a cascade of the Wiener type shows that the
      control of contrast sensitivity in the proximal retinal cells could be modeled by
      assuming the presence of a simple (static) saturation nonlinearity. Such a
      nonlinearity must exist somewhere between the horizontal cells and the amacrine
      cells. The functional implications of the contrast gain control are as follows:
      (a) neurons in the proximal retina exhibit greater sensitivity to input of lower
      contrast; (b) saturation of a neuronal response can be prevented because of the
      lower sensitivity for an input with large contrast, and (c) over a large range of
      modulation depths, the amplitude of the response remains approximately constant.

PMID- 7561749
TI  - The hepatitis B virus X gene: analysis of functional domain variation and gene
      phylogeny using multiple sequences.
AB  - The hepatitis B virus (HBV) X gene shares sequences with both the polymerase and
      precore genes, carries several regulatory signals critical to the replicative
      cycle, and its product has a transactivating function. In this study, the X gene
      sequences of 29 HBV strains from 14 different countries were characterized and
      compared to all corresponding databank sequences where the origin of the strain
      was stated. The X gene and its product are relatively well conserved. However,
      several rare or unique point mutations in the predicted X protein are described
      which further define regions on the primary sequence which may be of structural
      and/or functional significance. Phylogenetic analysis of the 29 X genes and their
      predicted proteins in this study using unrooted trees indicates that a common
      ancestral sequence gave rise to two main groups of X genes, represented by HBV
      strains found predominantly either in the Western or Eastern Hemisphere. In turn,
      each of these two main groups of sequences appear to have branched into two main
      lineages. Introduction of 33 additional DNA sequences from the databank has
      further verified these inferences and confirmed the groupings as previously
      described subgroups A to D. Whilst the split of X gene lineages into subgroups A
      and D seems feasible on geographical/anthropological grounds, the corresponding
      split of Eastern Hemisphere lineages into B and C may require an alternative
      hypothesis. Additionally, there was a correlation between the HBeAg/anti-HBeAg
      status of our patients and nucleotide identity at two positions in the core
      promoter, 52 and 50 bases upstream from the precore start codon. This finding,
      also shown recently by others, suggests that control of HBeAg secretion may
      involve mutations affecting transcription and not only precore/core translation.

PMID- 7561747
TI  - The voltage-activated hydrogen ion conductance in rat alveolar epithelial cells
      is determined by the pH gradient.
AB  - Voltage-activated H+ currents were studied in rat alveolar epithelial cells using
      tight-seal whole-cell voltage clamp recording and highly buffered, EGTA
      containing solutions. Under these conditions, the tail current reversal
      potential, Vrev, was close to the Nernst potential, EH, varying 52 mV/U pH over
      four delta pH units (delta pH = pHo - pHi). This result indicates that H+
      channels are extremely selective, PH/PTMA > 10(7), and that both internal and
      external pH, pHi, and pHo, were well controlled. The H+ current amplitude was
      practically constant at any fixed delta pH, in spite of up to 100-fold
      symmetrical changes in H+ concentration. Thus, the rate-limiting step in H+
      permeation is pH independent, must be localized to the channel (entry,
      permeation, or exit), and is not bulk diffusion limitation. The instantaneous
      current-voltage relationship exhibited distinct outward rectification at
      symmetrical pH, suggesting asymmetry in the permeation pathway. Sigmoid
      activation kinetics and biexponential decay of tail currents near threshold
      potentials indicate that H+ channels pass through at least two closed states
      before opening. The steady state H+ conductance, gH, as well as activation and
      deactivation kinetic parameters were all shifted along the voltage axis by
      approximately 40 mV/U pH by changes in pHi or pHo, with the exception of the fast
      component of tail currents which was shifted less if at all. The threshold
      potential at which H+ currents were detectably activated can be described
      empirically as approximately 20-40(pHo-pHi) mV. If internal and external protons
      regulate the voltage dependence of gH gating at separate sites, then they must be
      equally effective. A simpler interpretation is that gating is controlled by the
      pH gradient, delta pH. We propose a simple general model to account for the
      observed delta pH dependence. Protonation at an externally accessible site
      stabilizes the closed channel conformation. Deprotonation of this site permits a
      conformational change resulting in the appearance of a protonation site, possibly
      the same one, which is accessible via the internal solution. Protonation of the
      internal site stabilizes the open conformation of the channel. In summary, within
      the physiological range of pH, the voltage dependence of H+ channel gating
      depends on delta pH and not on the absolute pH.

PMID- 7561750
TI  - Properties of modified hepatitis B virus surface antigen particles carrying preS
      epitopes.
AB  - The current hepatitis B virus (HBV) vaccines contain the small (S) and middle (M)
      viral envelope proteins in particulate form but lack the large (L) protein.
      Although these particles elicit protective immunity to HBV, inclusion of the
      immunogenic preS1 region of the L protein may enhance their efficacy. To present
      preS1-derived epitopes on secretable subviral particles we rearranged the HBV
      envelope ORF by fusing part or all of the preS1 region to either the N or C
      terminus of the S protein. Fusion of the first 42 residues of preS1 to either
      site allowed efficient secretion of the modified particles and rendered the
      linked sequence accessible at the surface of the particle. Conversely, fusion of
      preS1 sequences to the C terminus of the M protein completely blocked secretion.
      This block to secretion could be rescued by provision of a heterologous N
      terminal signal sequence. All these particles displayed preS1, preS2 and S
      protein antigenicity. In mice, each construct elicited high titres of preS1
      specific antibodies which recognized the authentic L protein. Particles composed
      of the modified M protein also induced a preS2-specific response. Unexpectedly,
      however, neither particle elicited S protein-specific antibodies. Nonetheless,
      the genetic approach employed here represents a strategy to incorporate preS1
      derived epitopes both in high density and in highly immunogenic form into their
      authentic carrier matrix.

PMID- 7561746
TI  - Single-channel currents from diethylpyrocarbonate-modified NMDA receptors in
      cultured rat brain cortical neurons.
AB  - The role of histidine residues in the function of N-methyl-D-aspartate (NMDA)
      activated channels was tested with the histidine-modifying reagent
      diethylpyrocarbonate (DEP) applied to cells and membrane patches from rat brain
      cortical neurons in culture. Channels in excised outside-out patches that were
      treated with 3 mM DEP for 15-30 s (pH 6.5) showed an average 3.4-fold
      potentiation in steady state open probability when exposed to NMDA and glycine.
      Analysis of the underlying alterations in channel gating revealed no changes in
      the numbers of kinetic states: distributions of open intervals were fitted with
      three exponential components, and four components described the shut intervals,
      in both control and DEP-modified channels. However, the distribution of shut
      intervals was obviously different after DEP treatment, consistent with the single
      channel current record. After modification, the proportion of long shut states
      was decreased while the time constants were largely unaffected. Burst kinetics
      reflected these effects with an increase in the average number of openings/burst
      from 1.5 (control) to 2.2 (DEP), and a decrease in the average interburst
      interval from 54.1 to 38.2 ms. These effects were most likely due to histidine
      modification because other reagents (n-acetylimidazole and 2,4,6-trinitrobenzene
      1-sulfonic acid) that are specific for residues other than histidine failed to
      reproduce the effects of DEP, whereas hydroxylamine could restore channel open
      probability to control levels. In contrast to these effects on channel gating,
      DEP had no effect on average single-channel conductance or reversal potential
      under bi-ionic (Na+:Cs+) conditions. Inhibition by zinc was also unaffected by
      DEP. We propose a channel gating model in which transitions between single- and
      multi-opening burst modes give rise to the channel activity observed under steady
      state conditions. When adjusted to account for the effects of DEP, this model
      suggests that one or more extracellular histidine residues involved in channel
      gating are associated with a single kinetic state.

PMID- 7561748
TI  - Replication of baculovirus DNA.

PMID- 7561751
TI  - Epstein-Barr virus EBNA-LP and transcription regulation properties of pRB, p107
      and p53 in transfection assays.
AB  - The EBNA-LP protein (also known as EBNA-5) of Epstein-Barr virus (EBV) has been
      reported previously to colocalize in the nuclei of cells with the pRb protein and
      to bind in vitro to pRb and to the p53 protein, suggesting a role for EBNA-LP in
      modulation of the function of these proteins. Here we test in transfection assays
      whether EBNA-LP expression has any functional consequence for repression of E2F-1
      activity by pRb or p107 or for activation of transcription by the p53 protein. No
      significant effect could be found, although the assay systems were sensitive to
      the established effects of simian virus 40 large T antigen and human papillo
      mavirus type 16 E6 protein. There was very effective repression of GAL4/E2F-1
      transactivation by p107, consistent with earlier reports and indicating that p107
      can interact with the E2F-1 transactivation domain, even though p107 has been
      reported to bind specifically to E2F complexes containing E2F-4. The results
      indicate that, if the associations of EBNA-LP with pRB and p53 are
      physiologically relevant, they most likely affect other functions of these
      proteins or modulate their gene regulatory functions in ways that cannot be
      detected by transfection into cycling transformed cells.

PMID- 7561752
TI  - Selectable insertion and deletion mutagenesis of the human cytomegalovirus genome
      using the Escherichia coli guanosine phosphoribosyl transferase (gpt) gene.
AB  - We describe the mutagenesis of the IRSI-US5 region of the human cytomegalovirus
      genome, demonstrating the potential of the E. coli guanosine phosphoribosyl
      transferase (gpt) gene as a selectable marker for insertion and deletion
      mutagenesis of high passage (AD169, Towne) as well as low passage (Toledo)
      strains of virus. Despite evidence suggesting that the US3 gene product may play
      a regulatory role, disruption of this gene with a gpt insert had no effect on
      growth of any of these strains of virus in resting or dividing human fibroblasts,
      or in human thymus plus liver implants in SCID-hu mice. Transcripts of the gpt
      gene, under control of the herpes simplex virus thymidine kinase promoter
      adjacent to the US3 enhancer in the viral genome, accumulated with delayed early
      (beta) kinetics. Mutants with deletions in the IRS1 and US3-US5 regions were
      isolated by back-selection against gpt with the drug 6-thioguanine by growing
      virus in human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyl transferase
      deficient) skin fibroblasts immortalized with human papillomavirus oncogenes.
      Thus, we demonstrate a dependable method for insertion and deletion mutagenesis
      that can be applied to any region of the viral genome.

PMID- 7561753
TI  - Complete nucleotide sequence of the herpesvirus simiae glycoprotein G gene and
      its expression as an immunogenic fusion protein in bacteria.
AB  - The nucleotide sequence of a 2384 bp portion within the unique short (Us) region
      of the herpesvirus simiae (simian herpes B virus; SHBV) genome is presented. A
      partial and a complete open reading frame (ORF) were found within this nucleotide
      sequence. The partial ORF encodes the C terminus (147 amino acids) of a protein
      kinase which is highly conserved in the herpes simplex virus type 1 (HSV-1) and
      type 2 (HSV-2) and simian agent 8 (SA8) Us regions. The complete ORF is located
      3' to the partial ORF within the 2384 bp sequence and encodes a 593 amino acid
      glycoprotein which appears to be closely related to the SA8 glycoprotein G (gG),
      but shares little amino acid similarity with gG of HSV-1 and -2. However, the
      complete ORF shares certain features conserved among most alphaherpesvirus gGs,
      notably three highly conserved cysteine residues and an adjacent N-glycosylation
      site. Therefore, it was concluded that this complete ORF encodes the SHBV gG. The
      358 amino acid C-terminal portion of SHBV gG was expressed in Escherichia coli as
      a fusion protein and this was detected by immunoblotting with sera from
      cynomolgus monkeys which were either experimentally or naturally infected with
      SHBV. The purified fusion protein was inoculated into rabbits to raise an
      antiserum which recognized a number of apparently SHBV gG-specific protein bands
      in extracts from SHBV-infected simian cells.

PMID- 7561754
TI  - Analysis of cross reactivity of retrovirus proteases using a vaccinia virus-T7
      RNA polymerase-based expression system.
AB  - We have used the vaccinia virus-T7 RNA polymerase-based expression system for
      studies on the activity of proteases from various retroviruses on homologous and
      heterologous Gag polyproteins in eukaryotic cells. Proteases from human
      immunodeficiency virus (HIV) types 1 and 2, equine infectious anaemia virus,
      human T cell leukaemia virus type 1 and human spumavirus were produced and were
      shown to cleave their cognate Gag substrates produced in trans. Analysis of cross
      reactivity revealed that lentivirus proteases cleaved only lentivirus Gag
      proteins and oncovirus proteases acted primarily on oncovirus Gag proteins. The
      HIV-2 protease cleaved the HIV-1 Gag precursor almost as efficiently as HIV-1
      protease. Expression of the 5' end of the human spumavirus pol gene revealed that
      it encodes a functional protease that acts specifically on the human spumavirus
      Gag polyprotein. This assay will allow further investigation on the activity and
      specificity of retrovirus proteases in eukaryotic cells.

PMID- 7561755
TI  - Construction of human immunodeficiency virus 1/simian immunodeficiency virus
      strain mac chimeric viruses having vpr and/or nef of different parental origins
      and their in vitro and in vivo replication.
AB  - We constructed a series of human immunodeficiency virus 1 (HIV-1)/simian
      immunodeficiency virus strain mac (SIVmac) chimeric viruses having vpr and/or nef
      genes of either HIV-1 or SIVmac based on a chimeric virus with LTRs, gag, pol,
      vif and vpx derived from SIVmac and tar, rev, vpu and env from HIV-1. All of the
      chimeric viruses replicated in human and macaque peripheral blood mononuclear
      cells (PBMCs) and in several CD4+ human cell lines, though their growth
      potentials were slightly different depending on whether vpr and nef were from HIV
      1 or SIVmac, or were defective. The presence of nef accelerated replication in
      all the cells used and the replication of each chimera appeared to reflect that
      of the parental virus from which nef was derived. The presence of vpr had no
      clear effect in human and monkey PBMCs, but the replication of each chimera was
      influenced by the origin of vpr in H9 and A3.01 cells. NM-3rN, which carries HIV
      1 vpr and SIVmac nef, was inoculated intravenously into three rhesus monkeys,
      three cynomolgus monkeys and two pig-tailed monkeys. From 2 to 14 weeks after
      inoculation, viruses were consistently re-isolated from all the monkeys and virus
      loads were as high as that of SIVmac reported previously. The results indicate
      that infection with NM-3rN is more efficient than any of our previous chimeric
      viruses and suggest that NM-3rN, having HIV-1 Env, will be a useful challenge
      virus for evaluating AIDS vaccines based on HIV-1 Env in macaque monkeys instead
      of chimpanzees.

PMID- 7561756
TI  - Temporal patterns of feline immunodeficiency virus transcripts in peripheral
      blood cells during the latent stage of infection.
AB  - We have investigated the in vivo state of feline immunodeficiency virus (FIV)
      transcription in peripheral blood mononuclear cells (PBMC) of chronically FIV
      infected, asymptomatic cats. FIV was detected in a high percentage of PBMC but
      not in the plasma of these cats. By quantitative reverse transcription-PCR (RT
      PCR) analysis. FIV transcriptional status in the PBMC was characterized by
      extremely low or undetectable levels of unspliced or singly spliced mRNAs and
      predominantly multiply spliced mRNAs. Upon stimulation in vitro, however, the
      larger mRNA species and infectious virus production were rapidly induced in the
      PBMC. Furthermore, we demonstrated that viral production was induced in
      association with differential increases in the levels of each multiply spliced
      mRNA coding for FIV regulatory proteins. From these results, we suggest that
      replication of FIV is blocked at an early stage of gene expression in vivo, as
      described in asymptomatic human immunodeficiency virus (HIV) -infected patients,
      and that FIV infection in cats may be a useful model for clinical latency of HIV
      infection in man. Moreover, we propose that the replication of FIV in vivo may be
      controlled by the differential expression of each multiply spliced mRNA.

PMID- 7561758
TI  - Staggering disease in cats: isolation and characterization of the feline Borna
      disease virus.
AB  - A Borna disease virus (BDV)-like agent was isolated from the central nervous
      system (CNS) of cats with a spontaneous non-suppurative encephalomyelitis
      ('staggering disease'). In contrast to the rabbit-adapted BDV strain V, which can
      be propagated in several primary and permanent cell cultures, the cat virus grew
      only in embryonic mink brain cells. Infection of adult Wistar rats with feline
      brain tissue material did not result in clinical disease during a period of 5
      months, nor in growth of infectious virus in the brain. However, using the brain
      suspension of a newborn rat inoculated with feline brain tissue material, it was
      possible to induce typical Borna disease (BD) in four adult rats. This indicates
      a possible adaptation of the cat virus during passages in rats. By the use of an
      RT-PCR technique, BDV-specific RNA could be detected in a majority of brain
      samples from diseased cats. BDV-specific antigen was demonstrated in feline CNS
      samples both by immunohistochemistry and ELISA. However, the amount of BDV RNA
      and BDV antigen was less in the cats as compared to horses with BD, providing
      further support for the notion that a distinct feline BDV strain exists.

PMID- 7561760
TI  - Site-specific alteration of transmissible gastroenteritis virus spike protein
      results in markedly reduced pathogenicity.
AB  - The pathogenicity of neutralization-resistant mutants of the enteric coronavirus
      transmissible gastroenteritis virus (TGEV) was examined in the newborn piglet.
      The parental virus (Purdue-115 strain), as well as several mutants selected using
      monoclonal antibodies (MAbs) directed to antigenic sites A and B, caused an acute
      enteritis with 100% mortality. By contrast, most of the site D (MAb 40.1) mutants
      exhibited a strongly reduced enteropathogenicity, leading to the survival of
      animals inoculated with up to 1000-fold the 100% lethal dose of parental virus.
      Such a phenotypical change was correlated with point mutations or a small
      deletion, all located within the S gene sequence coding for the Pro-145 to Cys
      155 segment of the mature polypeptide. These observations suggest that an N
      terminal subregion of the S molecule is an essential determinant for pathogenesis
      in TGEV infection.

PMID- 7561759
TI  - Comparison of equine arteritis virus isolates using neutralizing monoclonal
      antibodies and identification of sequence changes in GL associated with
      neutralization resistance.
AB  - Three murine monoclonal antibodies (MAbs) that neutralize equine arteritis virus
      (EAV) infectivity were identified and characterized. The antibodies, 93B, 74D(B)
      and 38F, recognized the major envelope glycoprotein (GL) encoded by open reading
      frame (ORF) 5 in immunoblots and by immunoprecipitation. All three MAbs were used
      to compare the Bucyrus isolate of EAV and MAb neutralization-resistant (NR)
      escape mutants with the vaccine virus and 19 independent field isolates of EAV by
      virus neutralization. The different abilities of the MAbs to neutralize virus
      isolates indicated that they recognize non-identical epitopes. Susceptibility to
      virus neutralization could not be used to distinguish viruses from acutely and
      persistently infected horses. Comparison of the ORF 5 nucleotide and deduced
      amino acid sequence from NR and neutralization-sensitive virus isolates revealed
      amino acid sequence changes at positions 99 and 100 which correlate with the NR
      phenotype. Additional unique changes in the amino acid sequence of MAb NR viruses
      at positions 96 and 113 may also contribute to neutralization resistance. The
      sequence data further showed that the Bucyrus-derived viruses contain one N
      glycosylation site, whereas the field isolates DL8 and DL11 possess two sites,
      both of which are used. Most of the non-conservative amino acid sequence changes
      were located within the second half of the N-terminal hydrophilic domain.
      Sequence changes within the first half of the N-terminal ectodomain, the
      predicted transmembrane domain and the C-terminal hydrophilic domain were mainly
      silent base substitutions or resulted in conservative amino acid substitutions,
      suggesting that these regions of the protein are functionally conserved.

PMID- 7561757
TI  - In vitro transcription and polymerase binding studies of the termini of influenza
      A virus cRNA: evidence for a cRNA panhandle.
AB  - An in vitro transcription assay was used to study transcription from synthetic
      RNA corresponding to the 3' terminus of influenza A virus cRNA. Micrococcal
      nuclease-treated influenza virus ribonucleoprotein was used as a source of active
      polymerase complex. Mutations at two regions of the 13 nucleotide-long conserved
      cRNA 3' terminus were shown to reduce transcription templated by the short added
      model RNAs. The first region, at positions 1 and 2 from the 3' terminus, was
      shown to be affected by the exact nature of the dinucleotide primer used in the
      in vitro transcription reactions and may not be relevant in vivo. The second
      region, centred on positions 11 and 12, may be involved in base pairing with
      conserved nucleotides at the 5' terminus of the cRNA. Evidence for this comes
      from the finding that RNA corresponding to 5' conserved sequences, but mutated to
      restore the postulated base pairing with the mutated 3' ends, could partly
      restore transcription. Binding of the influenza virus polymerase complex to a set
      of 5'-mutated RNAs was investigated using a photochemical cross-linking assay.
      Specific binding to two regions of the cRNA 5' terminus was demonstrated, at
      positions 1 to 3 and positions 8 to 10. Together, these observations suggest that
      a panhandle forms from the termini of the cRNA molecule and that this structure
      may play a role in transcription to produce virion RNA.

PMID- 7561762
TI  - Paralysis caused by acute myelitis in Theiler's murine encephalomyelitis virus
      strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal
      cord.
AB  - Intravenous infection by Theiler's murine encephalomyelitis virus strain GD VII
      causes acute encephalomyelitis and paralysis in infected mice. However, nude mice
      and cyclophosphamide-treated ddY mice did not show paralysis when they were able
      to survive until day 20 post-infection (p.i.). Of ddY mice infected with 5 x
      10(7) p.f.u./mouse, 70-80% showed symptoms of paralysis on day 20 p.i. The viral
      titres in the brain and spinal cord in infected mice were not significantly
      different between paralytic and non-paralytic mice. In all of the mice infected
      with the virus, CD4+ lymphocytes and CD8+ lymphocytes had infiltrated the brain
      on days 10, 12, 14 and 20 p.i. as demonstrated by flow cytometric analysis. In
      contrast, few T lymphocytes infiltrated the spinal cord in the non-paralytic
      mice. Administration of an anti-CD4 monoclonal antibody (MAb) or anti-T cell
      receptor-alpha beta MAb on day 6 p.i. inhibited paralysis until day 20 p.i.,
      though 20% of the MAb-treated mice and 80% of the control mice showed paralysis.
      Administration of anti-CD8 MAb was not effective in the suppression of paralysis.
      The MAb treatment did not significantly augment viral replication in the spinal
      cord, although the viral titres in the brain of the MAb-treated mice increased
      significantly. After the transfer of spleen cells from infected C3H mice, the
      recipient mice infected with a small amount of the virus showed paralysis, though
      uninfected mice did not. This transfer could be blocked by CD4+ lymphocyte
      depletion of the donor mice. These results indicate that paralysis caused by
      acute myelitis in Theiler's virus strain GD VII infection is induced by CD4+
      lymphocytes infiltrating the spinal cord.

PMID- 7561761
TI  - Flavivirus-cross-reactive, HLA-DR15-restricted epitope on NS3 recognized by human
      CD4+ CD8- cytotoxic T lymphocyte clones.
AB  - The role of flavivirus-cross-reactive T lymphocytes in recovery from and
      pathogenesis of flavivirus infections is not known. In the present paper, we have
      defined a flavivirus-cross-reactive epitope recognized by two CD4+ CD8- cytotoxic
      T lymphocyte (CTL) clones, JK4 and JK43. The T cell clones were established from
      the peripheral blood T lymphocytes of a dengue-4-immune donor, using a limiting
      dilution method with dengue-4 antigen. These two T cell clones were cross
      reactive for dengue virus types 1, 2, 3 and 4, yellow fever virus and West Nile
      virus, and recognized NS3 protein. The smallest synthetic peptide recognized by
      these T cell clones was an identical 9 amino acid peptide which contains amino
      acids 146 to 154 (VIGLYGNGV) of dengue-4 NS3. HLA-DR15 was the restriction allele
      for recognition of this epitope by JK4 and JK43. JK4 and JK43 both used T cell
      receptor V alpha 8, but JK4 used V beta 8 and JK43 used V beta 2. This result
      indicates that this epitope is recognized by two flavivirus-cross-reactive CD4+ T
      cell clones which originated from different T cells in vivo.

PMID- 7561763
TI  - The complete sequence of a cucumber mosaic virus from Ixora that is deficient in
      the replication of satellite RNAs.
AB  - A cucumber mosaic virus (CMV-Ix) from Ixora is unusual in that it does not
      support the accumulation of some well-characterized CMV satellite RNAs in plants.
      CMV-Ix can support a particular satellite RNA variant which causes lethal tomato
      necrosis when inoculated with other CMV strains but not when inoculated with CMV
      Ix. This difference in ability to support accumulation of specific satellite
      variants is apparent even when their sequences differ by only 10 nucleotides.
      Electroporation of tomato protoplasts with combinations of CMV-Ix or CMV-1 RNA
      plus the same satellite variants showed similar differences in accumulation,
      indicating a defect in satellite RNA replication and not movement or
      encapsidation. Pseudorecombinant virus infections between CMV-1 and CMV-Ix
      indicated that the genomic determinants responsible for this phenotype reside on
      RNA 1 since only combinations with CMV-Ix RNA 1 failed to replicate satellite
      RNA. The complete genome of CMV-Ix was cloned, sequenced and compared with the
      genomes of other cucumoviruses. CMV-Ix is most similar in RNA and protein
      sequence to subgroup 1 CMV-Fny and CMV-Y but slightly less similar than they are
      to each other. CMV-Ix and all cucumovirus strains sequenced thus far share a
      domain in the 3' untranslated portion of their genomic RNAs in which 39 of 40
      bases are completely conserved.

PMID- 7561764
TI  - A citrus exocortis viroid variant from broad bean (Vicia faba L.): infectivity
      and pathogenesis.
AB  - A viroid present in very low titres was isolated from symptomless field broad
      bean plants. It was identified as a variant of citrus exocortis viroid in the T2,
      V and C domains. Infection of several hosts resulted in a change in the
      composition of the viroid population. Serial passage through tomato and back to
      the host of origin, broad bean, resulted in major changes in replication
      efficiency, host range and pathogenicity. The unique nucleotide sequence
      differences identified in the original broad bean variant were not conserved
      after passage through alternative hosts. The effects of these sequence variations
      on viroid secondary structure result in nonpathogenic viroid variants which can
      remain unnoticed in certain plant species but may act as reservoirs of viroid
      disease.

PMID- 7561765
TI  - Movement and transmission of banana bunchy top virus DNA component one in
      bananas.
AB  - The systemic movement and replication of banana bunchy top virus (BBTV) DNA
      component one were investigated. Strand-specific RNA probes and PCR were used to
      indicate the presence of the virus in various parts of infected banana plants
      during infection on the basis of dsDNA replicative intermediates of BBTV. The
      strand-specific probes were not only able to detect the presence of the virus but
      also gave an indication of where the virus replicated. The results using both the
      virion sense and complementary to virion sense specific probes were essentially
      the same indicating that BBTV initially replicated for a short period at the site
      of inoculation, and subsequently moved down the pseudostem to the basal
      meristematic region and ultimately into the roots and newly formed leaves. The
      virus was detected in the leaves formed prior to inoculation after 21 days using
      PCR but was not detected by the RNA probes. This indicated that the virus had the
      ability to move into these leaves but may not have replicated or accumulated to
      significant levels. The appearance of multimeric forms of BBTV suggested that the
      virus may have replicated via a rolling circle mechanism. Additionally, BBTV DNA
      component one did not appear to replicate in its aphid vector, Pentalonia
      nigronervosa.

PMID- 7561766
TI  - Complementation of African cassava mosaic virus AC2 gene function in a mixed
      bipartite geminivirus infection.
AB  - We have previously demonstrated that African cassava mosaic virus (ACMV) DNAs A
      and B efficiently complement the systemic spread of tomato golden mosaic virus
      (TGMV) DNA A when co-agroinoculated onto Nicotiana benthamiana. Here, we show
      that a mixture of an ACMV DNA A AC2 mutant and DNA B that is normally unable to
      systemically infect N. benthamiana can do so at low frequency when co
      agroinoculated with TGMV DNA A. Analysis of viral DNA showed that the AC2
      mutation was retained during infection. The mixture of genomic components was sap
      transmissible, indicating that systemic infectivity is not specifically
      attributable to the use of agroinoculation. In the presence of TGMV DNA A, ACMV
      coat protein as well as the DNA B gene products BV1 and BC1 were detected in
      systemically infected tissues. The results demonstrate that dysfunctional AC2 can
      be complemented in planta by its TGMV homologue AL2.

PMID- 7561767
TI  - Transmission by aphids of a naturally non-transmissible plum pox virus isolate
      with the aid of potato virus Y helper component.
AB  - Two Spanish plum pox virus (PPV) isolates, 5.15 and 3.3, were used in
      transmission experiments involving the aphid vector Myzus persicae, with woody
      and herbaceous host plants. These isolates differ in the size of their coat
      protein (CP) and sequence analysis revealed that isolate 3.3 has a 15 amino acid
      deletion near the N terminus of the CP, affecting the same positions as in a
      previously reported non-aphid-transmissible PPV isolate from Germany. Aphid
      transmission experiments showed that isolate 5.15 was transmitted from infected
      plants whereas isolate 3.3 was not. In contrast, both isolates were readily aphid
      transmitted when acquired through artificial membranes from purified virus
      preparations supplemented with purified helper component (HC) obtained from
      potato virus Y-infected plants. This indicates that non-transmissibility of
      isolate 3.3 may be due to a defect in the HC rather than in the CP.

PMID- 7561768
TI  - Expression of the tomato ringsport nepovirus movement and coat proteins in
      protoplasts.
AB  - Tomato ringspot nepovirus (TomRSV) produces a 45 kDa movement protein and a 58
      kDa coat protein in infected plants. Accumulation of the movement protein in
      relation to that of the coat protein was studied in infected protoplasts using a
      monoclonal antibody against the movement protein and polyclonal antibodies
      against the coat protein. Unlike most other viral movement proteins, the TomRSV
      movement protein was present at late stages of infection. Pulse-chase labelling
      experiments revealed that the release of the movement protein from the precursor
      polyprotein was coordinated with that of the coat protein. However, the movement
      protein was less stable than the coat protein in the extractable fraction of the
      protoplasts. The expression pattern of the TomRSV movement protein is discussed
      in the light of the proposed mechanism of cell-to-cell movement of virus-like
      particles through tubular structures composed of the movement protein.

PMID- 7561770
TI  - Localization of cis-acting sequences essential for cymbidium ringspot tombusvirus
      defective interfering RNA replication.
AB  - The smallest defective interfering RNA (DI-2) of cymbidium ringspot tombusvirus
      (CyRSV) was used to identify the cis-acting sequences necessary for its
      replication by making a series of deletions throughout the 404 nt long molecule
      and testing the biological activity of mutants. Deletion or substitution of the
      conserved sequence blocks (A, B and C) always yielded inactive molecules. The
      deletion of only a few nucleotides could be tolerated beyond the natural deletion
      sites in blocks A and B. However, either half of block C1 (34 nt) and the first
      25 nt of C2 (102 nt) could be deleted without loss of infectivity. It was also
      demonstrated that either one of the two halves of block C1 was specifically
      required for replication. We suggest that the last 77 nt of the viral genome and
      either half of block C1 represent the complementary strand promoter sequence
      recognized by the viral replicase.

PMID- 7561769
TI  - Complete sequence of an infectious full-length cDNA clone of citrus tatter leaf
      capillovirus: comparative sequence analysis of capillovirus genomes.
AB  - The complete nucleotide sequence of citrus tatter leaf capillovirus (CTLV lily
      strain) was determined. It is 6496 nucleotides long, excluding the 3'-terminal
      poly(A) tract, and contains two putative overlapping open reading frames (ORFs).
      ORF1 (positions 37-6354) encodes a potential polyprotein of molecular mass 242
      kDa. ORF2 (positions 4788-5750) codes for a 36 kDa protein. The 242 kDa
      polypeptide contains several non-structural protein domains (i.e.
      methyltransferase, NTP-binding helicase, papain-like proteinase and polymerase)
      and, at its C terminus, the putative coat protein. The N-terminal region of the
      36 kDa protein displays sequence similarity to the cell-to-cell movement proteins
      of the '30 K superfamily'. Such a genome structure is conserved between CTLV and
      apple stem grooving capillovirus. Capped transcripts from a plasmid containing
      the complete sequence of CTLV, with a T7 RNA promoter, successfully infected
      Chenopodium quinoa plants and caused symptoms characteristic of CTLV. Uncapped
      transcripts were noninfectious.

PMID- 7561771
TI  - Nucleotide sequence of the NS5 gene of Banzi virus: comparison with other
      flaviviruses.
AB  - Banzi is a mosquito borne flavivirus which belongs to the Uganda S serocomplex.
      No nucleotide sequence data have previously been reported from any virus of this
      serocomplex. We have determined the nucleotide sequence of the NS5 gene from
      Banzi virus and the predicted amino acid sequence was elucidated. Previously
      identified conserved RNA polymerase, methyltransferase and flavivirus NS5 amino
      acid motifs were present in the Banzi virus NS5 protein. These data add to the
      evidence for the functional importance of the regions. The encoded amino acid
      sequence was compared with the predicted amino acid sequence of other flavivirus
      NS5 proteins. Analysis of these sequences suggested that Banzi virus is most
      closely related to the mosquito-borne flaviviruses and, in particular, yellow
      fever virus. This pattern of similarity is in accordance with the previously
      suggested serological classification of flaviviruses.

PMID- 7561772
TI  - Novel genotypes of hepatitis C virus in Thailand.
AB  - We examined 24 C-type hepatitis specimens from Thailand and detected hepatitis C
      virus (HCV) RNA in all of them by RT-nested PCR for a portion of the HCV 5' non
      coding (5' NC) region and a portion of the HCV core region. However, we failed to
      detect HCV RNA in 11 specimens by RT-nested PCR for a portion in the non
      structural protein 5 (NS5) region that has been used commonly for HCV genotyping.
      We designed a new primer set for a separate portion of the NS5 region. Using this
      primer set, we succeeded in amplifying this portion in all 24 specimens. Two
      novel HCV genotypes, tentatively designated HCV-VII and HCV-VIII, were identified
      by sequencing these amplified regions. Our newly designed primers for RT-nested
      PCR may be useful for diagnosing infection as well as for genotyping unidentified
      HCV genomes.

PMID- 7561773
TI  - Hepatitis C virus variants from Thailand classifiable into five novel genotypes
      in the sixth (6b), seventh (7c, 7d) and ninth (9b, 9c) major genetic groups.
AB  - Nine (10%) out of 90 hepatitis C virus (HCV) isolates from hepatitis patients and
      commercial blood donors in Thailand were not classifiable into any of genotypes
      I/1a, II/1b, III/2a, IV/2b, V/3a or VI/3b by RT-PCR with type-specific primers
      deduced from the HCV core gene. These isolates were sequenced over a 1.6 kb
      stretch of the 5'-terminal sequence and 1.1 kb of the 3'-terminal sequence
      covering 30% of the entire genome. Based on two-by-two comparison and
      phylogenetic analyses of the nine Thailand isolates among themselves and with
      known full or partial sequences of previously reported HCV isolates, the Thailand
      isolates were classified into five genotypes not reported previously, viz. 6b,
      7c, 7d, 9b and 9c. Along with HCV isolates reported already, they make at least
      nine major genetic groups of HCV which further break down into at least 28
      genotypes with sequence similarity in the E1 gene (576 bp) of < or = 80%. As many
      more HCV isolates of distinct genotypes are expected to be found throughout the
      world, it will become increasingly difficult to classify them by comparison of
      any partial sequences of the genome. Complete sequence data will be required for
      the full characterization and classification of HCV genotypes.

PMID- 7561774
TI  - Association of hepatitis C virus particles with immunoglobulin: a mechanism for
      persistent infection.
AB  - The physical properties of hepatitis C virus (HCV) particles were determined by
      ultracentrifugation on 20-60% isopycnic sucrose density gradients. We report that
      (i) two populations of HCV particles were found in the sera of patients with
      chronic HCV infection [at high density (1.186-1.213 g/ml) and at low density
      (1.099-1.127 g/ml)], (ii) virus particles with high density values were
      associated with immunoglobulin, and (iii) virus particles with low density values
      accumulated base changes within a hypervariable region (HVR) of the E2 envelope
      domain of the RNA genome. The results indicate that base changes within the HVR
      of E2 lead to the accumulation of immunoglobulin-free virus particles. Therefore,
      these findings imply that persistent HCV infection is established as a
      consequence of sequence variation in the E2 envelope domain.

PMID- 7561775
TI  - Tripartite genome organization of a natural type 2 vaccine/nonvaccine recombinant
      poliovirus.
AB  - Intertypic vaccine/vaccine recombinant polioviruses are frequently isolated from
      vaccine-associated paralytic poliomyelitis cases (VAPP). We identified a
      vaccine/nonvaccine poliovirus recombinant as the causative agent of a lethal
      VAPP. Partial RNA sequencing revealed a tripartite recombinant structure of the
      viral genome. This consisted of a central capsid core of vaccine origin flanked
      by two units of nonvaccine origin. The first nonvaccine genomic unit spanned the
      whole 5' noncoding region, and the second one almost the entire nonstructural
      protein-coding region and the 3' noncoding region. Amino acid and nucleotide
      sequence similarities in the 3' and 5' unidentified regions indicated that the
      viral donor(s) were poliovirus species, suggesting recombination between a
      vaccine-derived and a wild poliovirus. The nonvaccine donor(s) could not be
      identified among the investigated wild polioviruses cocirculating in the same
      geographical area. This is the first report of a natural recombination event
      occurring in the 5' genomic extremity of poliovirus. The neurovirulence for
      transgenic mice and the pathogenicity for humans of the recombinant suggested
      that the modular genomic organization of this virus might have conferred a
      selective advantage over its vaccine parent.

PMID- 7561777
TI  - Assembly of double-layered virus-like particles in mammalian cells by
      coexpression of human rotavirus VP2 and VP6.
AB  - Development in mammalian cells of a recombinant expression system that mimics the
      rotavirus capsid assembly process would be advantageous for studying the
      structural requirements for particle formation. To this end, we investigated the
      ability of a recombinant vaccinia virus system to produce double-layered virus
      like particles. The genes coding for VP2 and VP6 proteins of the human rotavirus
      strain Wa were cloned and used to generate recombinant vaccinia viruses.
      Metabolic labelling of CV-1 cells infected with these recombinant viruses
      followed by immunoprecipitation with a polyclonal antiserum directed to Wa virus
      showed that VP2 and VP6 were efficiently expressed. The recombinant proteins were
      similar in size and immunoreactivity to authentic rotavirus proteins. Biochemical
      and electron microscopy analyses demonstrated that simultaneous expression of VP2
      and VP6 in mammalian cells resulted in the formation of intracellular spherical
      particles resembling double-layered rotavirus particles.

PMID- 7561776
TI  - Human enteric Caliciviridae: the complete genome sequence and expression of virus
      like particles from a genetic group II small round structured virus.
AB  - Comparisons of the RNA polymerase and capsid sequences of small round structured
      viruses (SRSVs) have recently shown these are genetically diverse viruses which
      fall into two distinct groups. The genomes of two group I viruses, Southampton
      and Norwalk viruses have been characterized; however, similar data for the
      genetic group II SRSVs have not been available until now. We report here the
      complete genome sequence of a recent group II SRSV, Lordsdale virus. The
      Lordsdale virus genome is 7555 nt in length and has a similar organization to the
      group I SRSVs. The large ORF in the 5' half of the genome (5100 nt) is shorter
      than the group I SRSV ORF1 (5367 nt), but has the characteristic 2C helicase, 3C
      protease and 3D RNA polymerase enzyme motifs. ORF2, encoding the structural
      protein is of a similar size to the group I viruses but the small 3'-terminal ORF
      is significantly larger in group II. A highly conserved sequence of 28 nt was
      identified at the start of Lordsdale virus ORF1 and repeated at the start of
      ORF2. These conserved motifs are typical of the animal caliciviruses. Comparison
      of the 150 N-terminal amino acids in the ORF1 protein revealed little identity
      between the two SRSV genetic groups, reflecting the shorter ORF1 in the group II
      virus. Recombinant baculoviruses containing ORF2 and ORF3 sequences were
      constructed and used to express large quantities of the group II Lordsdale virus
      structural protein. The capsid protein formed virus-like particles by self
      assembly which resembled 'empty' SRSVs.

PMID- 7561778
TI  - Immunogenicity of poliovirus B and T cell epitopes presented by hybrid porcine
      parvovirus particles.
AB  - We have analysed the potential capacity of hybrid porcine parvovirus (PPV)
      capsids to present foreign epitopes to the immune system. Foreign sequences were
      introduced into the N and C termini of PPV VP2, which was previously shown to
      assemble spontaneously into parvovirus-like particles. The integrity of the C
      terminus was shown to be essential for preserving the structure of the capsid and
      therefore could not be used for epitope fusion. In contrast, insertion of
      sequences corresponding to T and B cell poliovirus epitopes in the N terminus did
      not alter the formation of particles. Moreover, the chimeric capsids containing
      the C3:T epitope were able to induce a T cell response in vivo. However, hybrid
      particles containing the C3:B epitope fused to the N terminus did not induce any
      peptide-specific antibody response, suggesting that the inserted B cell epitope
      was not exposed at the surface of the particles. These results show that the N
      terminus in PPV empty capsids is not an adequate site for insertion of B cell
      epitopes, but may be useful for T cell epitope presentation and suggest that the
      N terminus is located in an internal position.

PMID- 7561779
TI  - The equine herpesvirus 1 gene 63 RING finger protein partially complements
      Vmw110, its herpes simplex virus type 1 counterpart.
AB  - All alpha herpesviruses of known DNA sequence have been found to encode a protein
      with similarities to immediate early protein Vmw110 (ICP0) of herpes simplex
      virus type 1 (HSV-1). The conserved portion of this family of proteins is a
      characteristic zinc binding module, known as a RING finger or C3HC4 domain.
      Examples of RING finger domains occur in many other proteins of diverse
      evolutionary origin and function. Recently, the solution structure of the equine
      herpesvirus 1 (EHV-1) RING finger protein, encoded by gene 63, has been solved.
      To investigate whether this structure could be considered to be a paradigm of
      herpesvirus RING domains, we have constructed a recombinant HSV-1 which expresses
      the EHV-1 gene 63 protein (EHVg63) in place of Vmw110. Comparison of the growth
      properties of the recombinant with those of wild-type and Vmw110-defective
      viruses indicates that EHVg63 is able to fulfil partially, but not completely,
      the roles of Vmw110 during virus growth in tissue culture.

PMID- 7561780
TI  - Defective entry of herpes simplex virus types 1 and 2 into porcine cells and lack
      of infection in infant pigs indicate species tropism.
AB  - We have determined if a defect at entry of the human pathogen herpes simplex
      virus type 1 (HSV-1) into cultured porcine cells extends to HSV-2 and if the poor
      susceptibility of porcine cells for these viruses is indicative of in vivo
      species tropism. HSV-1 replicates poorly in swine testis (ST) and other porcine
      cells which lack a functional non-heparan sulphate receptor(s) required for virus
      entry. By several criteria, ST cells resist infection by either HSV-1 or HSV-2.
      Infection can be restored if normal entry is bypassed by PEG-mediated virion-cell
      membrane fusion. Neither HSV serotype infects, replicates or produces clinical
      symptoms in infant pigs. No virus was isolated from any of multiple sites and
      seroconversion did not occur. The in vitro defect in porcine cells blocking HSV
      entry correlates with, and is likely to be at least partly responsible for, in
      vivo resistance of pigs to infection.

PMID- 7561782
TI  - A glycoprotein E deletion mutant of bovine herpesvirus 1 infects the same limited
      number of tissues in calves as wild-type virus, but for a shorter period.
AB  - To gain insight into the role of glycoprotein E of bovine herpesvirus 1 (BHV-1),
      we compared the distribution of wild-type (wt) BHV-1 with that of a gE deletion
      mutant (gE-) in calves after intranasal inoculation. The wt-infected calves had
      severe clinical signs, but the gE(-)-infected calves were virtually free of
      clinical signs. At 3, 4, 7, 8, 44, 45, 50 and 51 days post-infection (p.i.), one
      calf from each group was killed and tissues were collected for virus isolation
      and PCR analysis. At 3, 4, 7 and 8 days p.i., infectious virus could be isolated
      only from the nasopharyngeal mucosa, parotid gland and nearby lymphoid tissues
      for both the wt- and gE(-)-infected calves. At 3 and 4 days p.i., virus titres in
      these tissues were comparable in both the wt- and gE(-)-infected calves. However,
      the virus titres were significantly reduced at 7 and 8 days p.i. in the gE(-)
      infected calves, but not in the wt-infected calves. Semi-quantitative PCR
      analysis revealed that for the entire infection period (3 to 51 days p.i.)
      significantly more BHV-1 DNA was detected in the trigeminal ganglia (TG) of the
      wt-infected calves than in those of the gE(-)-infected calves. We conclude that
      the gE- mutant infects the same limited number of tissues as wt BHV-1, but for a
      shorter period.

PMID- 7561781
TI  - CD4 down-modulation by ganglioside and phorbol ester inhibits human herpesvirus 7
      infection.
AB  - Recently, data demonstrating that CD4 is an essential component of the receptor
      for human herpesvirus 7 (HHV-7) as well as for human immunodeficiency virus have
      been accumulating. Since gangliosides and phorbol esters are known to induce
      selective down-modulation of cell surface CD4 expression, it might be expected
      that treatment with these agents would interfere with HHV-7 infection of CD4+ T
      cells. The present study, undertaken to verify this possibility, demonstrated
      that addition of monosialoganglioside-GM1 or 12-O-tetradecanoylphorbol 13-acetate
      effectively induced disappearance of CD4 from the cell surface and also reduced
      HHV-7 infectivity, as judged by the CPE on virus-infected cells and studies of
      indirect immunofluorescence, TCID50 and semi-quantitative PCR of the HHV-7
      genome. Taken together with previous studies, the present data strongly suggest
      that the CD4 molecule is a critical component of the receptor for HHV-7.

PMID- 7561783
TI  - Vaccinia virus serpins B13R and B22R do not inhibit antigen presentation to class
      I-restricted cytotoxic T lymphocytes.
AB  - Vaccinia virus (VV) inhibits the presentation of certain epitopes from influenza
      virus nucleoprotein (NP), haemagglutinin (HA) and non-structural 1 (NS1) proteins
      to CD8+ cytotoxic T lymphocytes (CTL) by an unknown mechanism. We have
      investigated whether VV genes B13R and B22R, which encode proteins with amino
      acid similarity to serine protease inhibitors (serpins), are involved in this
      process. Recombinant VVs were constructed which express influenza virus proteins
      HA, NP or NS1 and which lack serpin gene B13R or both B13R and B22R. The lysis of
      cells infected with these viruses by influenza virus-specific CD8+ CTL was
      compared to the lysis of cells infected with viruses expressing both the
      influenza proteins and the serpin genes. Cytotoxicity assays showed that deletion
      of the VV serpin genes B13R and B22R and other genes between B13R and B24R did
      not increase the level of lysis, indicating that these genes are not involved in
      inhibition of antigen presentation of the epitopes tested.

PMID- 7561784
TI  - Experimental African swine fever: apoptosis of lymphocytes and virus replication
      in other cells.
AB  - In order to determine the cause of cellular death of lymphocytes in pigs with
      acute African swine fever and the relationships between African swine fever virus
      (ASFV) and interstitial cells, ten pigs were inoculated with a highly virulent
      strain of ASFV (Malawi '83) and samples taken for ultrastructural study of
      hepatic and renal interstitial tissues. We demonstrated death by apoptosis of
      lymphocytes and virus replication in fibroblasts, smooth muscle cells and
      endothelial cells in the interstitial tissues of pigs inoculated with ASFV. From
      day 5 onwards, apoptotic lymphocyte and intense virus replication in hepatic
      interstitial macrophages and fibroblasts were observed. By day 7, apoptotic
      lymphocytes and virus replication in macrophages, interstitial capillary
      endothelial cells and fibroblasts in the kidney were observed. Virus replication
      was also seen in smooth muscle cells of hepatic and renal arterioles and venules.
      Our results suggest that mononuclear phagocyte system (MPS) cell activation, and
      the resulting release of cytokines, could induce apoptosis of lymphocytes and
      virus replication in non-MPS cells.

PMID- 7561785
TI  - Organization of the major and minor capsid proteins in human papillomavirus type
      33 virus-like particles.
AB  - The organization of the major (L1) and minor (L2) proteins in the human
      papillomavirus capsid is still largely unknown. In this study we analysed the
      disulphide bonding between L1 proteins and the association of L2 proteins with
      capsomers using virus-like particles obtained in insect cells by co-expression of
      the L1 and L2 genes of human papillomavirus type 33. About 50% of the L1 protein
      molecules in these particles (1.29 g/cm3) formed disulphide-bonded trimers.
      Reduction of the intermolecular disulphide bonds by dithiotreitol (DTT) treatment
      caused disassembly of virus-like particles into capsomers. This indicates that
      disulphide bonds between capsomers at the threefold symmetry positions of the
      capsid are essential for the assembly of the papillomavirus capsid. In contrast,
      the L2 protein was not engaged in intermolecular disulphide bonding. The L2
      protein remained associated with capsomers on disassembly by treatment with DTT.
      When the disassembly was carried out in 0.65 M-NaCl, complete L2 protein
      molecules bound preferentially to capsomer oligomers, whereas truncated L2
      protein molecules bound only to monomers. In 0.15 M-NaCl only complete L2 protein
      molecules remained bound to capsomers. This indicates that different regions of
      the L2 protein molecule are differentially involved in the association of the
      papillomavirus capsid.

PMID- 7561786
TI  - Semiquantitative anti-HBc IgM detection in children with chronic hepatitis B: a
      long-term follow-up study.
AB  - Serum anti-HBc IgM titres were monitored monthly by a semiquantitative method in
      14 children with HBeAg positive chronic hepatitis B followed up for 18-65 months.
      All patients, but one, were treated with alfa-interferon (IFN) at different
      times. On the whole, 12 flare-up episodes were observed and 7 patients cleared
      HBV-DNA and seroconverted to anti-HBe. Seroconversion occurred only in patients
      with pretreatment anti-HBc IgM index greater than 0.15 and serum HBV-DNA
      concentration below 100 pg/ml; the pretreatment alanine aminotransferase (ALT)
      value was not predictive of response. Combining anti-HBc IgM results and serum
      HBV-DNA levels observed during the pre-IFN period allowed a precise
      identification of patients who were likely to respond to IFN therapy. Patients
      who seroconverted to anti-HBe showed a progressive reduction in serum anti-HBc
      IgM titres within 6 months. Interestingly, one child, in whom HBV-DNA reappeared
      and who reconverted to HBeAg 7 months after treatment, showed no anti-HBc IgM
      decrease after the transient clearance of HBV-DNA and anti-HBe seroconversion.
      Semiquantitative anti-HBc IgM detection is a useful tool in the decision making
      process for children with chronic hepatitis B.

PMID- 7561787
TI  - Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of
      human peripheral blood mononuclear cells in vivo.
AB  - Out of 64 cases of non-Hodgkin's lymphomas (NHL), 55 cases of Hodgkin's disease
      (HD) and 31 cases of multiple sclerosis (MS), 2 NHL, 7 HD and 1 MS cases were
      found positive by polymerase chain reaction (PCR) for the presence of HHV-6
      sequences in pathologic lymph nodes of the lymphomas and in peripheral blood
      mononuclear cells (PBMCs) of MS. A further analysis of the PBMCs of the PCR
      positive cases by standard Southern blot technique revealed only 2 NHL, 3 HD and
      1 MS cases as positive, indicating that these six patients have an unusually high
      viral copy number in the PBMCs. Restriction analysis, carried out using probes
      representative of different regions of the virus, showed that three cases retain
      only a deleted portion of the viral genome. In the remaining three cases a
      complete viral genome was present, containing the right end sequences in which
      the rep-like gene, possibly crucial to the viral and cellular life cycle, is
      located. The analysis by pulsed field gel electrophoresis (PFGE) of the total DNA
      of the PBMCs obtained directly, without culture from PBMCs of these last three
      cases (1 NHL, 1 HD, and 1 MS), using the same probes, showed the absence of free
      viral molecules and the association of viral sequences with high molecular weight
      DNA. These results are consistent with in vivo integration of the entire virus in
      the cellular genome. A further study of the same patients with chromosome
      fluorescence in situ hybridization (FISH) showed in all the three cases the
      presence of a specific hybridization site, located at the telomeric extremity of
      the short arm of chromosome 17 (17p13), suggesting that this location is at least
      a preferred site of an infrequent, but possibly biologically important,
      integration phenomenon.

PMID- 7561788
TI  - Detection of several types of human papilloma viruses in AIDS-associated Kaposi's
      sarcoma.
AB  - Epidemiological studies indicate that acquired immunodeficiency syndrome (AIDS)
      associated Kaposi's sarcoma (KS) may be caused by an infectious, preferentially
      sexually transmitted agent. Infections with human papilloma viruses are common,
      sexually transmitted diseases occurring frequently in homosexual men, who are
      also the main risk group for developing KS. In order to evaluate the possible
      role of HPV in the development of KS, 24 cutaneous AIDS-associated Kaposi's
      sarcomas were investigated by the polymerase chain reaction (PCR) and by in situ
      hybridization for the presence of human papilloma viruses (HPV). HPV DNA
      sequences were detected in 5 of 24 KS specimens, in 4 of 13 normal skin specimens
      from AIDS patients without KS and in 5 of 14 skin specimens of HIV-seronegative
      patients. For the first time, HPV types 6 and 33 were detected by PCR in KS. A
      higher proportion of HPV types 16/18 was found in AIDS-associated KS specimens,
      whereas HPV type 33 was seen more often in normal skin specimens of the control
      group. Apart from the known HPV types 16/18 described in KS, this study
      demonstrates also the presence of HPV 6 and 33 in this condition.

PMID- 7561789
TI  - Enzyme immunoassay using baculovirus-expressed human calicivirus (Mexico) for the
      measurement of IgG responses and determining its seroprevalence in London, UK.
AB  - The use of an enzyme immunoassay (EIA) employing a baculovirus-expressed
      recombinant human calicivirus (Mexico virus, MxV) for the detection of IgG
      specific antibodies is described. MxV appeared to be related antigenically to a
      strain of small round structured virus, SRSV/UK4/Leeds/91, which had previously
      been shown by solid phase immune electron microscopy (SPIEM) to be related to
      Snow Mountain agent (SMA). One other outbreak which occurred in San Anita, USA in
      1980 and was due to consumption of contaminated water was caused by a virus
      antigenically related to MxV. Volunteers and patients who developed significant
      IgG responses to rMxV showed anamnestic IgG responses (2 to 4-fold) in the
      recombinant Norwalk virus (rNV) IgG assay. Patients and volunteers who were known
      to have been infected with several other strains of calicivirus/small round
      spherical viruses (SRSV) including NV and SRSV UK3 showed no significant antibody
      response to rMxV in the EIA. A seroepidemiological survey of sera from 338
      children in London showed that infection with MxV occurred earlier in life than
      NV. Primary infections with MxV were common after the age of 6 months. Over 70%
      of children had evidence of infection by the ages of 2 years, whereas only 12% of
      these children had been infected with NV. High concentrations of maternal
      antibody were present during the first month of life which was detected in 96% of
      the neonates. The results suggest that the high sensitivity of the EIA may be
      detecting maternal antibody throughout the first 8 months of life.

PMID- 7561790
TI  - Nucleotide sequence of hepatitis B virus isolated from subjects without serum
      anti-hepatitis B core antibody.
AB  - The nucleotide sequences of the precore/core and X open reading frames (ORFs) of
      hepatitis B virus (HBV) were studied in four subjects who were serologically
      negative for anti-hepatitis B core antibody. These subjects were positive for
      serum hepatitis B surface antigen and were considered to be asymptomatic HBV
      carriers. Sequencing of the precore/core ORF revealed precore wild type and 3 to
      8 nucleotide substitutions (replacing 0 to 2 amino acids) in the core region
      compared with the sequence of subtype adr. These substitutions were not
      considered to have changed the epitope of the core antigen, resulting in the
      absence of anti-HBc as determined by a conventional diagnostic kit. The X ORF
      showed 1 to 5 nucleotide substitutions (replacing 1 to 3 amino acids) and the
      structure of the X protein and the core promoter/enhancer II complex appeared to
      be conserved. These findings strongly suggest that the absence of serum anti-HBc
      is not due to mutation of the HBV DNA but to an aberrant immune reaction of the
      host to HBV.

PMID- 7561793
TI  - Cytotoxic factors released by dengue virus-infected human blood monocytes.
AB  - Human monocyte-derived cytotoxic factors (CF) induced by dengue virus were
      studied. Using several human leukemia cell lines as precursors, the biological
      activities of CF in conditioned medium from dengue virus-infected monocytes were
      demonstrated through the measurement of tumor cell growth inhibition. The
      conditioned medium from dengue virus infected monocytes suppressed significantly
      growth of CEM, HL60, K562, and U937 cells. In the presence of 10% conditioned
      medium (v/v) from dengue virus infected monocytes, DNA synthesis of U937 cells,
      as measured by [3H]thymidine incorporation, decreased by 99% in contrast to their
      synthesis in conditioned medium from noninfected control monocytes, which did not
      have any suppressive effect. Partial characterization of CF showed that it is a
      proteinase-K-sensitive and heat-labile protein with a molecular mass over 100
      kDa. Employing a flow cytometric analysis of the cell cycle, it was found that
      U937 cells, treated either with conditioned medium from dengue virus infected
      monocytes or with CF, but not treated with conditioned medium from noninfected
      monocytes, showed cell-cycle arrest in G1 phase by 48 hr. This suppressive effect
      of CF on U937 growth was dose- and time-dependent. These results suggest that
      dengue virus-infected monocytes may produce CF to target myeloid cells, resulting
      in the hematological changes observed in patients with dengue fever.

PMID- 7561792
TI  - Absence of human papillomavirus DNA from esophageal carcinoma as determined by
      multiple broad spectrum polymerase chain reactions.
AB  - Strong evidence has implicated human papillomaviruses (HPV) in the pathogenesis
      of anogenital cancers and a number of other mucosal and cutaneous lesions. Data
      concerning the involvement of HPV in esophageal cancers are controversial.
      Different investigators have detected HPV types (mainly types 16 and 18) in
      biopsy specimens of esophageal cancers. A study was undertaken to determine
      whether responses to chemotherapy of advanced squamous cell carcinomas could be
      correlated with the HPV status. Polymerase chain reaction (PCR) amplification was
      used for the detection of HPV DNA in biopsies of esophageal squamous cell
      carcinomas treated with either surgical resection alone (n = 42) or chemotherapy
      followed by surgical resection (n = 21). Different general and consensus PCR
      primer sets, which allow the detection of most of the known as well as a number
      of not yet characterized HPV types, were used. HPV DNA was not detected in any of
      the 61 esophageal squamous cell carcinomas, suggesting that HPV infections are
      not likely to play a major role in the etiology of this neoplasm.

PMID- 7561794
TI  - Genetic susceptibility to herpetic encephalitis of inbred rabbits of B/Jas
      strain.
AB  - Inbred rabbits of B/Jas strain were found to be highly susceptible to herpes
      simplex virus type 1 encephalitis, following i.v. injection of the virus, while
      Chbb:HM strain rabbits were not susceptible. The susceptibility trait seemed to
      be inherited recessively, involving multiple genes, because (B/Jas x Chbb:HM)F1
      hybrids were as resistant as Chbb:HM rabbits, and because more than 90% of
      backcrosses of (B/Jas x Chbb:HM)F1 to B/Jas were resistant to viral inoculation.
      The encephalitis in B/Jas rabbits resembled human herpes simplex encephalitis, in
      that the temporal lobe as well as the brain stem were affected preferentially,
      leading to the development of various types of seizures, such as circling, loss
      of balance leading to a fall, and tonic and clonic convulsions. The disease could
      be diagnosed by magnetic resonance imaging (MRI) analysis before onset of
      seizures, and diseased rabbits showed a marked lymphopenia at onset of seizures.

PMID- 7561791
TI  - Persistence of extrahepatic hepatitis B virus DNA in the absence of detectable
      hepatic replication in patients with baboon liver transplants.
AB  - The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well
      documented. Whether HBV DNA can persist in extrahepatic tissues for long periods
      of time in the absence of replication in the liver has not been determined
      previously. Recently, two patients with end-stage liver disease secondary to
      chronic active HBV were treated with baboon liver xenotransplants as these
      animals are felt to be resistant to HBV infection. Multiple tissues from these
      two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV
      DNA was not detectable in four of five samples of the liver xenografts. A
      positive signal was observed in a single assay for one sample, but this sample
      was not positive in subsequent assays. HBV DNA was detected in peripheral blood
      lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small
      intestine. The level of HBV DNA in these tissues was too low for the detection of
      HBV DNA replicative intermediates by Southern hybridization; thus, it could not
      be determined whether the HBV DNA in these tissues represented actively
      replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in
      infiltrating lymphocytes, or deposition of HBV immune complexes originating from
      the plasma. However, it is clear from this study that HBV DNA persisted in
      multiple tissues for 70 days after replication in the liver had ceased or at
      least was below the level of detection by PCR.

PMID- 7561795
TI  - Serial density analysis of hepatitis C virus particle populations in chronic
      hepatitis C patients treated with interferon-alpha.
AB  - In interferon treatment of chronic hepatitis C patients, the biochemical and
      virological responses mostly parallel each other. However, some patients who show
      persistent ALT normalization display continued viremia after cessation of
      therapy. High-density hepatitis C virus (HCV) particles, which are immune complex
      forms, are reported to be less infectious both in vitro and in vivo. To assess
      whether high-density HCV contributes to the response discrepancies and to clarify
      the association with patient outcome, sera were examined from chronic hepatitis C
      patients who were treated with interferon-alpha. This study included 10 sustained
      responders with viremia (SR + ve), 5 SR without viremia, 3 transient responders
      (TR), and 3 nonresponders (NR). The SR + ve patients were defined as those with
      continued ALT normalization and serum HCV-RNA positivity at 24 weeks after
      therapy completion. Serum samples obtained before and 24 weeks after therapy were
      ultracentrifuged on 35% sucrose. The ratio between high-density and low-density
      HCV was determined by quantification of HCV-RNA titers in the bottom and top
      fractions by competitive reverse transcription and by the polymerase chain
      reaction, and expressed as the bottom/top (B/T) ratio. The B/T ratios before
      therapy were 1:1 in all groups of patients, and 1:1 after therapy in TR and NR
      groups. Five out of 6 SR + ve patients who showed 1:1 ratio after therapy
      relapsed within 1 year. In contrast, all SR + ve patients whose ratios were 10
      100:1 continued to show ALT normalization. These findings demonstrate that
      patients who have high-density HCV dominance after therapy show persistent ALT
      normalization despite viremia, which can be explained by predominance of the
      neutralized immune complex.

PMID- 7561796
TI  - Reverse transcriptase mutations in sequential HIV-1 isolates in a patient with
      AIDS.
AB  - Sequential human immunodeficiency virus type 1 (HIV-1) isolates were obtained
      over a 29-month period from a person before, during, and after AZT therapy. DNA
      sequence analysis of polymerase chain-amplified reverse-transcriptase gene showed
      a gradual accumulation of mutations to peak resistance (IC50 2.13 microM AZT) in
      association with mutations at codons 44, 210, and 369, as well as at 41, 67, 70,
      and 215. Eight months after cessation of AZT therapy, when an HIV-1 isolate from
      the patient was again sensitive to AZT, these mutations had all returned to the
      pretherapy sequence.

PMID- 7561798
TI  - Injection with nondisposable needles as an important route for transmission of
      acute community-acquired hepatitis C virus infection in Taiwan.
AB  - A prospective case-controlled study was conducted in order to determine the
      transmission route of community-acquired hepatitis C virus (HCV) infection in
      Taiwan. Thirty-eight consecutive patients (25 men and 13 women) with acute
      community-acquired HCV infection and 76 age (within 3 years)- and sex-matched
      healthy control subjects without HCV infection were enrolled. Serum anti-HCV was
      tested by second generation immunoassay. The sera of 26 family members from 12
      families of index patients were also tested for anti-HCV. A questionnaire
      covering the history of blood transfusion, surgery, intravenous drug abuse,
      prostitute contact, dental procedures, injection, acupuncture, tattooing, and ear
      piercing was conducted among patients and control subjects. Univariate analysis
      revealed injection with nondisposable needles was an independent risk factor (P =
      0.02, odds ratio = 4.17, 95% confidence interval = 1.24-14.47) associated with
      HCV infection. Other risk factors were not significant. Only 2 (7.7%) family
      members of index patients had an anti-HCV. In conclusion, more vigorous effort to
      prohibit the use of nondisposable needles should be promoted to interrupt the
      spread of community-acquired HCV infection in Taiwan. Of note, a significant
      number of patients (34.2%) contracted HCV infection without identifiable risk
      factors. Unidentified routes need to be investigated.

PMID- 7561797
TI  - Hepatitis E virus antibodies among patients with hemophilia, blood donors, and
      hepatitis patients.
AB  - The presence of antibodies to hepatitis E virus (HEV) was studied among
      hemophiliacs, blood donors, and hepatitis patients. Four of 296 (1.4%)
      hemophiliacs and 5 of 1,275 (0.4%) donors were confirmed as positive for HEV
      antibodies (difference was not significant: P = 0.07). Parenteral transmission of
      HEV to hemophiliacs was thus rare or nonexistent. Seven of 187 hepatitis patients
      were found with HEV antibodies (IgG and IgM). Six persons fell ill shortly after
      arriving from HEV-endemic countries. The seventh patient, without a history of
      travel, represents a case of nontropical hepatitis E. Consequently, hepatitis E
      should be considered in patients suffering from acute non-ABC hepatitis, even in
      industrialized countries.

PMID- 7561799
TI  - Oral brivudin vs. intravenous acyclovir in the treatment of herpes zoster in
      immunocompromised patients: a randomized double-blind trial.
AB  - The efficacy of oral brivudin vs. intravenous acyclovir was compared in a
      randomized multicentered study under double-blind conditions using the double
      dummy technique. Forty-eight patients with a herpes zoster rash less than 72
      hours in duration were entered in the study. Brivudin was given as one 125-mg
      tablet every 6 hours. Acyclovir was infused over 1 hour at a dose of 10 mg/kg
      every 8 hours. Treatment was continued for 5 days. There was no significant
      difference between the treatment groups when analyzed in terms of new lesion
      formation, increase in the area of rash within the primary dermatome, cutaneous
      dissemination, and affection of mucous membranes or visceral organs. Both
      treatment regimes were also equally effective in the time to full crusting of
      lesions. Oral brivudin and intravenous acyclovir were well tolerated by most
      patients. There was no need to interrupt the treatment in any case. As effective
      as intravenous acyclovir in the treatment of herpes zoster, oral brivudin offers
      the potential for outpatient treatment of herpes zoster in immunocompromised
      patients.

PMID- 7561800
TI  - Long-term follow-up of hepatitis B virus and hepatitis C virus replicative levels
      in chronic hepatitis patients coinfected with both viruses.
AB  - Dual infection with hepatitis B and C viruses is often encountered in endemic
      areas of both viruses. However, understanding of the clinical and virological
      implications is limited. The aim of this study was to investigate the role of
      each virus in liver injury and the interaction between the two viruses in dual
      infection with hepatitis B and C viruses. Three patients who had chronic
      infection with both hepatitis B and C viruses were examined, and a longitudinal
      study of both serum hepatitis B virus DNA and hepatitis C virus RNA levels over 4
      years was undertaken. The results were correlated with serum alanine
      aminotransferase levels. Serum alanine aminotransferase values showed a
      relationship with hepatitis B virus replicative levels, but not with hepatitis C
      virus replicative levels in all 3 patients. Serial changes of replicative levels
      of both viruses were studied, and it was found that hepatitis C virus replicative
      levels were enhanced after the decline of hepatitis B virus replication in 1 of
      the 3 patients. In the remaining 2 patients, a transient rise of hepatitis C
      virus replicative levels in association with a decrease of hepatitis B virus
      replication was also observed during part of the follow-up period. These findings
      indicate that hepatitis B virus may play a dominant etiological role in liver
      injury, and that a suppressive action between hepatitis B and C viruses may occur
      in dual infection with both viruses.

PMID- 7561801
TI  - Prediction of relapses after interferon-alpha therapy by hepatitis C virus RNA in
      peripheral blood mononuclear cells.
AB  - To investigate the predictive value of hepatitis C virus (HCV)-RNA in peripheral
      blood mononuclear cells in the response to interferon therapy in patients with
      chronic hepatitis C, 15 patients with histologically proven chronic active
      hepatitis and who were positive for serum HCV-RNA were treated with interferon
      alpha (6 million units; i.m.) every day for two weeks and then three times a week
      for 22 weeks. Ten of the 15 patients were responders whose alanine
      aminotransferase levels decreased to the normal range at the end of interferon
      therapy. In four of the 10 responders, HCV-RNA was not detected by reverse
      transcription-polymerase chain reaction in peripheral blood mononuclear cells nor
      in serum at the end of treatment. These four patients were complete responders,
      with alanine aminotransferase levels remaining normal for the next 24 weeks. In
      five of the 10 responders, HCV-RNA was detected in peripheral blood mononuclear
      cells but not in serum at the end of treatment. All of these relapsed within the
      next 24 weeks. In the remaining responder, HCV-RNA was detected both in
      peripheral blood mononuclear cells and in serum at the end of treatment. This
      responder also had a relapse within the next 24 weeks. Five of the 15 patients
      were non-responders, in whom HCV-RNA was detected both in peripheral blood
      mononuclear cells and in serum. Thus, detection of HCV-RNA in peripheral blood
      mononuclear cells may be a good clinical marker to predict relapse after
      interferon treatment.

PMID- 7561803
TI  - Detection of cytomegalovirus DNA in cerebrospinal fluid in immunocompetent
      patients as a sign of active infection.
AB  - Detection of cytomegalovirus (CMV) DNA by the polymerase chain reaction (PCR) in
      samples of cerebrospinal fluid (CSF) has been shown to be a sensitive method of
      diagnosing CMV disease in the central nervous system. Since CMV causes latent
      infection in white blood cells, an unanswered question is whether detection of
      latent CMV DNA in the cell fraction of CSF samples by PCR is possible in
      seropositive patients. In a prospective study, the finding of CMV DNA in CSF of
      CMV seropositive patients with suspected viral infection of the central nervous
      system (CNS) was evaluated clinically. Fractionation of 64 CSF samples from
      seropositive patients was carried out before analysing the samples for CMV DNA by
      PCR. In four of the five patients who had CMV DNA in the cell pellet and/or
      supernatant, the clinical data suggested CMV-associated neurological disease. The
      remaining 59 samples were negative in both pellet and supernatant. In addition,
      11 CSF samples with high cell counts from patients with bacterial meningitis were
      examined for CMV DNA and found to be negative in 10 patients and positive in 1.
      One hundred thirty two uncentrifuged CSF samples were used as negative controls.
      The results of the study indicate that detection of CMV DNA in CSF samples by PCR
      correlated well with disease and was not due to latent CMV infection.

PMID- 7561802
TI  - High prevalence of hepatitis B, C, and E markers in young sexually active adults
      from the Central African Republic.
AB  - The Central African Republic is located in tropical Africa, where both the human
      immunodeficiency virus (HIV) and hepatitis B virus (HBV) are highly endemic. The
      exact prevalence of hepatitis C virus (HCV) and hepatitis E virus (HEV) markers
      in this country is unknown. The aim of the study was to determine, according to
      HIV and HBV serostatus, the prevalence of these markers in young sexually active
      adults in the Central African Republic. One hundred and fifty-seven consecutive
      patients attending the National Centre for Sexually Transmitted Diseases in
      Bangui were included. The following serological markers were examined: (i) anti
      HIV1 and anti-HIV2 antibodies; (ii) markers of HBV infection; (iii) anti-HCV
      antibodies; (iv) anti-HEV antibodies. Anti-HIV1 antibodies were found in 31 of
      the 157 patients (20%). The prevalence of anti-HBc antibodies, reflecting
      exposure to HBV, was 140/157 (89%) and 45 had detectable anti-HBs antibodies.
      Twenty-two patients (14%) were chronic carriers of hepatitis B surface antigen
      (HBsAg), but only one was HBe antigen-positive. Anti-HCV antibodies were found in
      8 persons (5%) and anti-HEV antibodies in 38 (24%). No difference was found in
      the prevalence of these markers according to the presence or absence of anti-HIV
      antibodies. This study confirms the high rate of HIV infection, HBV exposure and
      chronic carriage of HBsAg in sexually active young adults in the Central African
      Republic. A high prevalence of HCV markers was found in this population, similar
      to that reported in neighbouring countries, together with a high rate of HEV
      markers, suggesting that HEV is endemic in this region.

PMID- 7561804
TI  - Fatal illness associated with a new hantavirus in Louisiana.
AB  - A fatal case of hantaviral illness occurred in Louisiana, outside of the range of
      P. maniculatus, the rodent reservoir for Sin Nombre virus. Hantavirus RNA and
      antigens were detected in patient autopsy tissues, and nucleotide sequence
      analysis of amplified polymerase chain reaction (PCR) products identified a newly
      recognized unique hantavirus, provisionally named Bayou virus. Prominent features
      of the clinical illness are compatible with hantavirus pulmonary syndrome (HPS),
      but several features such as renal insufficiency and intraalveolar hemorrhage are
      more compatible with hemorrhagic fever with renal syndrome (HFRS), a disease
      associated with Eurasian hantaviruses.

PMID- 7561806
TI  - Dissociation and vulnerability to psychotic experience. The Dissociative
      Experiences Scale and the MMPI-2.
AB  - Prior research on the MMPI has cautioned against misdiagnosing schizophrenia in
      patients with dissociative identity disorder. The present study examined the full
      spectrum of the dissociative experience in relation to MMPI-2 profiles. Ninety
      eight women in treatment for trauma-related disorders completed the Dissociative
      Experiences Scale and the MMPI-2 in routine inpatient diagnostic evaluations.
      Consistent with prior research, severe dissociation was associated with high
      elevations on MMPI-2 scales typically associated with psychotic symptoms.
      Contrary to hypotheses, the ostensibly most benign form of dissociation,
      absorption and imaginative involvement, was somewhat more strongly related to
      MMPI-2 scores than the more pathognomonic forms of dissociation,
      depersonalization and amnesia. Although it should not be misdiagnosed, severe
      impairment on the MMPI in conjunction with dissociation should be taken seriously
      as suggesting vulnerability to psychotic experience. The dissociative retreat
      from the stressors of outer reality opens the door to the inner world of
      traumatic images and affects, along with compromised reality testing and
      disorganized thinking.

PMID- 7561805
TI  - Immunogenicity and safety of a new inactivated hepatitis A vaccine in a
      comparative study.
AB  - A multicentre, controlled, randomised, open, comparative trial including 839
      healthy adult volunteers was carried out in order to compare the immunogenicity
      and reactogenicity of two vaccines against hepatitis A virus (HAV) during primary
      immunization and after booster injection. The first vaccine was produced by
      Pasteur Merieux (PM), and the second vaccine by Smith-Kline Beecham (SKB). The
      vaccination schedule consisted of 2 doses (months 0, 6) for PM and 3 doses
      (months 0, 1, and 6) for SKB. Two weeks after the first dose, the seroconversion
      rates among initially HAV seronegative subjects (n = 608) were 93.4% and 76.1%
      for the PM and SKB vaccines, respectively, the corresponding geometric mean
      titres (GMTs) were 59.0 mIU/ml versus 30.8 mlU/ml (modified RIA HAVAB assay,
      Abbott Laboratories). Two months after the beginning of immunization (one dose
      versus two doses) the GMTs were 138.4 and 161.6 mlU/ml, respectively. At month 7,
      the seroconversion rates were 100% for both vaccines, and the GMTs were 4,189 and
      3,163 mlU/ml, respectively. After the first dose of vaccine, 24.6% and 19.6% of
      the PM and SKB vaccines reported local reactions. The rates for systemic
      reactions were 27.2% and 25.0%, respectively. Lower rates for local and systemic
      reactions were seen after booster injections and statistical differences were not
      observed between the two vaccines. The study also demonstrated that vaccination
      was as well tolerated in subjects with anti-HAV antibodies as in HAV seronegative
      subjects. Logistic regression analysis revealed a significant vaccine effect on
      seroconversion rates only at week 2 (P < 10(-4). The same conclusions were drawn
      from the analysis of GMT by multivariate regression.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7561807
TI  - A controlled comparison of self-rated sleep complaints in acute and chronic
      nightmare sufferers.
AB  - A cross-sectional study was performed to retrospectively assess self-rated sleep
      complaints in three groups of subjects: controls without nightmares (N = 77),
      acute nightmares sufferers (< 6 months duration, N = 36), and chronic nightmare
      sufferers (> 6 months duration, N = 128). Four specific complaints of sleep
      disturbance were categorically measured to ascertain the presence or absence of
      the symptom: fear of going to sleep; awakenings from sleep; difficulty returning
      to sleep; and fitful, restless sleep. Each of the four separate sleep complaints
      were significantly more common in the acute (p < .0001) and chronic (p < .0001)
      nightmare groups compared with controls. A summed aggregate score of the four
      sleep complaints was also higher in both the acute (p < .0001) and chronic groups
      (p < .0001) compared with controls. Ninety-one percent of all subjects with
      nightmares reported at least one sleep complaint. Between-group assessments,
      comparing acute and chronic nightmare sufferers for any of the four variables and
      the aggregate, demonstrated no statistically significant findings, although a few
      trends were noted. A dose-response relationship was not observed for nightmare
      frequency or chronicity for any of the four sleep variables or their aggregate.
      The relationship between nightmares and disturbed sleep is discussed.

PMID- 7561808
TI  - Clinical presentation of disorders of extreme stress in combat veterans.
AB  - Disorders of extreme stress (DES), previously referred to as disorders of extreme
      stress not otherwise specified and/or complex posttraumatic stress disorder, is a
      proposed diagnosis designed to describe the symptom presentation of those
      repeatedly exposed to traumatic stressors. Little is known, however, about the
      applicability of DES to combat veterans. We clinically assessed combat veterans
      for the presence or absence of DES in order to provide descriptive clinical
      information about the severity and patterns of endorsement of DES symptoms among
      combat veterans. Results indicate that DES is relevant to veterans and the
      implications of these results for both diagnoses and treatment are discussed.

PMID- 7561810
TI  - Interpretation of symptom presentation and distress. A Southeast Asian refugee
      example.
AB  - Symptom expression or the manifestation of distress is greatly influenced by
      one's cultural background. This exploratory study investigated symptom
      presentation of distress among a community sample of Vietnamese, Chinese
      Vietnamese, Cambodian, and Lao refugees. The study examined whether or not the
      Western-designed distress measure used in the study was culturally sensitive
      enough to accurately capture culturally framed expressions of distress. The
      results of the factor analyses showed that the four Southeast Asian refugee
      groups did not express distress in three separate factors as devised in the
      original measure. Instead, a single robust factor emerged. The single factor
      comprised items from the depression, anxiety, somatic, and psychosocial
      dysfunction subscales. The items that made up the single factor strongly resemble
      the construct for the diagnosis of neurasthenia. Researchers have found
      neurasthenia to be a culturally sanctioned Asian cultural idiom of distress. The
      findings strongly suggested that this Southeast Asian refugee population
      expressed distress in a pattern of symptoms more consistent with Asian nosology.
      The clinical and research implications of the results of this exploratory study
      are also discussed.

PMID- 7561811
TI  - Cognitive-behavioral group treatment for social phobia in adolescents. A
      preliminary study.
AB  - The present study is a preliminary evaluation of the effectiveness of a new
      cognitive-behavioral group treatment protocol for social phobia in adolescents.
      Five adolescents with social phobia were treated in a 16-session group treatment
      program, with parental involvement in selected sessions. Treatment involved
      skills training (social skills, problem solving, assertiveness), cognitive
      restructuring, behavioral exposure, and homework. Self-report measures of anxiety
      and depression, taken throughout treatment, indicated significant improvements
      over a 1-year follow-up period. Behavior test measures also indicated a decrease
      in subjective anxiety ratings after treatment which was maintained at follow-up.
      Structured diagnostic interviews 1 year after treatment confirmed full remission
      of social phobia for four subjects, with one subject's phobia in partial
      remission. Overall, the present findings support the continued evaluation of this
      protocol for social phobic adolescents.

PMID- 7561812
TI  - Gender differences in schizotypic features in a large sample of young adults.
AB  - Research with self-report measures of schizotypic or psychosis-prone features in
      nonclinical populations suggests that, similarly to schizophrenic populations,
      males score higher on more "negative" schizotypic features and females score
      higher on more "positive" schizotypic features. We administered the Schizotypal
      Personality Questionnaire and the Chapman Scales of Psychosis Proneness-
      impulsivity/nonconformity, magical ideation, perceptual aberration, physical
      anhedonia, and social anhedonia--to a large, nonclinical, young adult sample (N =
      1179: 453 males and 726 females). Results indicated increased negative
      symptomatology in males compared with females, but not increased positive
      symptomatology in females compared with males. Findings on Schizotypal
      Personality Questionnaire factors suggested that interpersonal deficits differed
      by gender as well. Finally, a measure of impulsive behavior and nonconformity not
      typically associated with negative symptomatology indicated gender differences
      not predicted by a negative/positive dichotomy.

PMID- 7561813
TI  - Schizophrenia and strabismus.

PMID- 7561809
TI  - Posttraumatic stress disorder (PTSD) symptoms in PTSD patients' families of
      origin.
AB  - Posttraumatic stress disorder (PTSD) patients, psychiatric controls, and hospital
      employee controls rated their father, mother, and oldest sibling of each sex on
      14 PTSD Interview (PTSD-I) symptom ratings. The stress disorder patients assigned
      their relatives significantly higher PTSD-I ratings than the control group
      members did in 35 of 120 comparisons. The number of significant differences was
      nearly identical in the fathers, mothers, sisters, and brothers. Differences were
      particularly frequent on items pertaining to intrusive thoughts, impoverished
      relationships, and guilt. The results suggest that a trauma survivor's risk for
      PTSD may be related to his family's history for PTSD-like behaviors.

PMID- 7561814
TI  - Are depressive mood disturbances in adults with Down's syndrome an early sign of
      dementia?

PMID- 7561816
TI  - Paroxetine treatment of anger associated with depression.

PMID- 7561815
TI  - Dissociative symptoms in posttraumatic stress disorder subjects with a history of
      suicide attempts.

PMID- 7561817
TI  - Alcohol, cannabis, nicotine, and caffeine use and symptom distress in
      schizophrenia.
AB  - The high prevalence of substance use, e.g., alcohol and illegal and nonprescribed
      drugs, in schizophrenia is widely recognized. One explanation for this high
      prevalence is that substance use may be a self-initiated method for managing
      symptoms. To test whether the intake of four substances--alcohol, cannabis,
      nicotine, and caffeine--would increase with increases in symptom distress, daily
      self-reports of symptom distress and substance intake over 12 weeks were analyzed
      with pooled time series analyses. Compliance with neuroleptic medication was
      added to the analyses to control for any changes in prescribed medication
      compliance while using nonprescribed drugs or alcohol. Of the four substances
      studied, only nicotine was significantly related to symptom distress. Higher
      distress with prodromal symptoms was related to decreases in nicotine use.
      Analysis of caffeine did not meet the criteria for significance but does provide
      direction for further research. Higher distress, with neurotic symptoms, was
      related to increases in caffeine use. Further research is needed to clarify the
      relationship between nicotine and symptoms.

PMID- 7561818
TI  - Comparative effectiveness of three approaches to serving people with severe
      mental illness and substance abuse disorders.
AB  - This study examines the rationale for and relative effectiveness of three
      intervention models for treating people with severe mental illness and substance
      abuse disorders: Twelve Step recovery, behavioral skills training, and intensive
      case management. Using clinical trial methods, 132 dually diagnosed clients were
      assigned to three service approaches. Changes in client psychosocial outcomes,
      and psychiatric and substance abuse symptomatology were tracked over a 24-month
      period. Differential effectiveness was evident, with clients in the behavioral
      skills group demonstrating the most positive and significant differences in
      psychosocial functioning and symptomatology, compared with the Twelve Step
      recovery approach. However, the case management intervention also resulted in
      several positive and important differences compared with the Twelve Step recovery
      approach. We also found significant changes over time, not only at 6 months but
      increasingly positive changes in psychosocial functioning at 12 and 18 months as
      well. These results underscore the need for clinical trials to further examine
      the relative cost effectiveness of treatment approaches for dually disordered
      clients and to incorporate means of assessing subgroup differences so that the
      interventions being tested can be further refined and targeted to a broad set of
      needs among the dually diagnosed.

PMID- 7561819
TI  - Prior head injury in male veterans with borderline personality disorder.
AB  - This study evaluated the relationship between traumatic brain injury (TBI) and
      borderline personality disorder (BPD). Forty-three males with BPD were compared
      with 49 age- and sex-matched controls with other psychiatric diagnoses. The
      occurrence of TBI was identified by chart review. Head injury was identified in
      42% of patients meeting criteria for BPD but in only 4% of controls (p < .001).
      All patients but one had sustained a TBI prior to the diagnosis of BPD. The
      prevalence of TBI is higher in subjects with BPD than in controls. Since TBI
      occurred prior to the full expression of the BPD clinical syndrome, TBI appears
      to be a cause rather than the result of BPD.

PMID- 7561820
TI  - Borderline psychopathology and recurrences of clinical disorders.
AB  - This prospective cohort study of patients with borderline psychopathology reports
      on the clinical disorders occurring during the course and at 7-year follow-up.
      Subjects with persistent versus remitted borderline personality disorder (BPD)
      are compared. The relationship between the initial levels of borderline
      psychopathology and the occurrence of clinical disorders on follow-up is
      examined. Consecutive admissions to inpatient units were screened for borderline
      characteristics. This resulted in a sample of 130 subjects, 88 of whom were
      positive for BPD based on the Diagnostic Interview for Borderlines. At 7-year
      follow-up, 81 (62.3%) subjects were reinterviewed in person, 6 (4.6%) suicided, 2
      (1.6%) were decreased, 36 (27.7%) refused to participate, and 5 (3.8%) could not
      be located. Twenty-seven of 57 (47.4%) who initially were positive for BPD were
      rediagnosed at 7-year follow-up (the persistent group) and 30 (52.6%) were no
      longer diagnosed as BPD (the remitted group). The persistent individuals were
      significantly more likely to be diagnosed as having major depression, dysthymia,
      and other psychiatric disorders than the remitted group. The persistent group had
      significantly more episodes of substance abuse over the follow-up period compared
      with the remitted group. Individuals with persistent BPD suffered more episodes
      of clinical disorders over the follow-up period and the initial level of
      borderline psychopathology predicted the recurrence of major depression.

PMID- 7561821
TI  - Family history of DSM-III-R dramatic personality disorder cluster and functioning
      in patients with major depressive disorder.
AB  - Clinicians and researchers have noted that personality dysfunction related to
      borderline personality significantly predicts a poorer course in major depressive
      disorder. There is also some evidence that some aspects of personality are
      heritable. The goal of this report was to determine whether family history of
      dramatic personality disorder cluster indicated differences in functioning in
      patients with major depressive disorder. Patients with major depression were
      divided into two groups: those with a family history of dramatic personality
      disorder cluster (N = 49) and those without (N = 22). These were the clinical
      groups. A screened normal group was also added to determine how far the clinical
      groups differed from ordinary functioning (N = 31). Compared with the other
      clinical group, the group with the family history of dramatic personality
      disorder tended, in general, to have fewer personality traits as measured by the
      Personality Disorder Examination, similar Hamilton Anxiety and Depression scores
      and several significantly better functioning measures. It appears that a family
      history of dramatic personality disorder cluster identifies a group with
      different, but not necessarily lower, levels of functioning. Implications of
      these findings are discussed.

PMID- 7561822
TI  - Temperament, character, and personality disorder in bulimia nervosa.
AB  - In a sample of 76 women participating in a clinical treatment trial for bulimia
      nervosa, we examined the clinical differences between subjects with and without
      concurrent personality disorders and the ability of "self-directedness" (a
      character scale of Cloninger's Temperament and Character Inventory) to predict
      the presence of personality disorder. Sixty-three percent of the sample had at
      least one personality disorder diagnosis. Fifty-one percent of personality
      disorders were in cluster C, 41% were in cluster B, and 33% were in cluster A.
      The presence of personality disorder was associated with greater depressive
      symptoms, worse global functioning, laxative use, greater body dissatisfaction,
      higher harm avoidance, and lower self-directedness. As hypothesized, low self
      directedness scores were associated with a markedly increased probability of a
      personality disorder.

PMID- 7561823
TI  - Unblinding in trials of the withdrawal of anticholinergic agents in patients
      maintained on neuroleptics.
AB  - The reason for the wide variation in relapse rates in trials of the withdrawal of
      anticholinergic agents in patients maintained on neuroleptics is unclear and
      could be due to bias introduced through unblinding. Forced-choice guesses of
      whether patients had been receiving active or placebo medication were made in a
      clinical trial. Correctness of guessing was correlated with measures of
      Parkinsonism. Raters' guesses were better than chance expectation and correlated
      with ratings of Parkinsonism. Nurses' guesses correlated with their own global
      measure of side effects but not with raters' measures. Patients' guesses were no
      better than chance. Unblinding of raters is a significant factor in
      anticholinergic withdrawal studies and preconceived notions of the value of
      anticholinergics could therefore be affecting the results of trials, helping to
      produce the wide variation in relapse rates.

PMID- 7561824
TI  - Delusional electronic dental implant: case reports and literature review.

PMID- 7561825
TI  - Posttraumatic somatoform disorders among immigrant workers.

PMID- 7561826
TI  - Retinal pigmented epithelium does not transdifferentiate in adult goldfish.
AB  - The neural retina of adult goldfish can regenerate from an intrinsic source of
      proliferative neuronal progenitor cells, but it is not known whether the retina
      can regenerate by transdifferentiation of the retinal pigmented epithelium (RPE),
      a phenomenon demonstrated in adult newts. In this study, we asked whether
      following surgical removal of the neural retina in adult goldfish the RPE was
      capable of autonomously transdifferentiating and generating new neural retina.
      The retina was prelabeled by injecting the fluorescent dye Fluoro-Gold (FG) into
      the eye prior to surgical removal; this procedure ensured that residual retina
      was labeled with FG and could therefore be distinguished from unlabeled,
      regenerated retina. To examine the time course of retinal regeneration, and to
      identify regenerated retinal neurons, the thymidine analogue bromodeoxyuridine
      was injected intraocularly, and retinas were examined up to 2 months later. We
      found that the RPE did not transdifferentiate; instead, retinas regenerated only
      when pieces of residual neural retina were left intact. Under these
      circumstances, newly regenerated cells derived from proliferating cells intrinsic
      to the residual neural retina. When retinas were completely removed, as was
      evident from a lack of FG labeling, there was no retinal regeneration.

PMID- 7561827
TI  - Development of midbrain and anterior hindbrain ocular motoneurons in normal and
      Wnt-1 knockout mice.
AB  - The effect of homozygotic Wnt-1-/- mutations on the development of ocular
      motoneurons was examined with the lipophilic dye DiI and compared to control and
      phenotypic wild-type mouse embryos. A piece of DiI-soaked filter paper was
      inserted into the orbit, the midbrain, or rhombomere 5 of the hindbrain in six
      paraformaldehyde-fixed litters (10.5, 12.5, and 14.5 days postcoitum) containing
      Wnt-1, Wnt+/-, and Wnt-1+/+ individuals and three control litters. We labeled all
      ocular motoneurons retrogradely and all relevant nerves anterogradely in all
      control and phenotypic wild-type animals. In all phenotypically identified Wnt-1
      /- mutants we could always label the abducens nerve and motoneurons and the optic
      fibers to the thalamus, but we were unable to label oculomotor or trochlear
      nerves or motoneurons. In addition to Wnt-1 knockout mutants, we also labeled
      mice from the WZT9B transgenic line carrying a lacZ reporter gene driven by the
      Wnt-1 gene enhancer. In these embryos we tested for co-localization of Wnt-1
      expression in biotinylated dextran amine-labeled ocular motoneurons using a newly
      developed technique. In younger embryos we obtained evidence for co-localization
      of the beta-galactosidase reaction product derived from lacZ gene activity in
      some retrogradely filled oculomotor motoneurons and adjacent to other oculomotor
      and the trochlear motoneurons. Acetylcholine esterase, a marker of early
      differentiating cholinergic neurons, showed a similar topology with respect to
      the lacZ reaction product. Thus, at least some future oculomotor motoneurons
      express Wnt-1, whereas others and the trochlear motoneurons caudal to the ventral
      midbrain expression of Wnt-1 may be exposed to the short range diffusion of the
      Wnt-1 gene product. Thus, the Wnt-1-/- mutation precludes formation or survival
      of midbrain and anterior hindbrain neurons, including oculomotor and trochlear
      motoneurons.

PMID- 7561828
TI  - Estrogens and non-estrogenic ovarian influences combine to promote the
      recruitment and decrease the turnover of new neurons in the adult female canary
      brain.
AB  - The higher vocal center (HVC) of the songbird forebrain exhibits persistent
      neurogenesis in adulthood, particularly in a region of the mediocaudal
      neostriatum that is associated with a subventricular layer of estrogen receptive
      cells. We asked whether estrogens might influence adult neurogenesis, by
      assessing the effect of ovariectomy on HVC neuronal production in the adult
      female canary. Fifteen 1-year-old females were separated into groups of
      ovariectomized, estradiol-replaced ovariectomized, and gonadally intact birds. To
      label dividing cells and their progeny, the birds were given [3H]thymidine for 8
      days, killed 32 days later, and their brains autoradiographed. A significant rise
      was noted in the number of HVC neurons per section in estradiol-treated birds
      relative to the untreated control birds. The number of [3H]thymidine-labeled HVC
      neurons was also higher in the estrogen-treated birds; however, the neuronal
      labeling index (LI) did not vary as a function of estradiol replacement, as the
      total number of HVC neurons rose in parallel with the added new neurons. In
      contrast, the neuronal LI did rise as a result of ovariectomy, and this
      ovariectomy-associated increase in the LI was not reversed by estradiol. Among
      non-neuronal cell types, the endothelial LI was higher in estrogen-treated birds
      than in their untreated counterparts, suggesting estrogen-associated
      angiogenesis. Radioimmunoassay confirmed that serum estradiol was reduced in the
      castrated birds. Since estrogen appeared to promote the survival of
      [3H]thymidine+ neurons, we next sought to determine whether estrogen acted
      directly on the newly generated neurons, or rather indirectly through an
      intermediary cell population. To this end, we asked whether the new neurons or
      their precursors expressed estrogen receptor immunoreactivity (ER-IR). Five adult
      male canaries were given [3H]thymidine for periods ranging from 2 to 28 days,
      killed at varying times up to 3 weeks thereafter, then probed for ER-IR and
      autoradiographed. [3H]thymidine+ cells displayed no detectable ER-IR within their
      first 4 weeks of postmitotic life. Rather, during migration from the ventricular
      zone (VZ), the new neurons traversed a layer of mitotically quiescent, ER+
      subventricular cells. Double labeling for ER-IR and cell-type selective antigens
      confirmed that these ER+ cells were neurons. These results indicate that the
      early survival of new neurons in the adult songbird HVC is promoted by estrogen,
      and may be mediated by the estrogen-stimulated paracrine release of neurotrophic
      agents by ER-IR subventricular neurons. Our data suggest that estrogen's
      promotion of neuronal survival may operate concurrently with an estrogen
      independent ovarian suppression of neuronal mitogenesis.

PMID- 7561829
TI  - Role of local nonspiking interneurons in the generation of rhythmic motor
      activity in the stick insect.
AB  - Local nonspiking interneurons in the thoracic ganglia of insects are important
      premotor elements in posture control and locomotion. It was investigated whether
      these interneurons are involved in the central neuronal circuits generating the
      oscillatory motor output of the leg muscle system during rhythmic motor activity.
      Intracellular recordings from premotor nonspiking interneurons were made in the
      isolated and completely deafferented mesothoracic ganglion of the stick insect in
      preparations exhibiting rhythmic motor activity induced by the muscarinic agonist
      pilocarpine. All interneurons investigated provided synaptic drive to one or more
      motoneuron pools supplying the three proximal leg joints, that is, the thoraco
      coxal joint, the coxa-trochanteral joint and the femur-tibia joint. During
      rhythmicity in 83% (n = 67) of the recorded interneurons, three different kinds
      of synaptic oscillations in membrane potential were observed: (1) Oscillations
      were closely correlated with the activity of motoneuron pools affected; (2)
      membrane potential oscillations reflected only certain aspects of motoneuronal
      rhythmicity; and (3) membrane potential oscillations were correlated mainly with
      the occurrence of spontaneous recurrent patterns (SRP) of activity in the
      motoneuron pools. In individual interneurons membrane potential oscillations were
      associated with phase-dependent changes in the neuron's membrane conductance.
      Artificial changes in the interneurons' membrane potential strongly influenced
      motor activity. Injecting current pulses into individual interneurons caused a
      reset of rhythmicity in motoneurons. Furthermore, current injection into
      interneurons influenced shape and probability of occurrence for SRPs. Among
      others, identified nonspiking interneurons that are involved in posture control
      of leg joints were found to exhibit the above properties. From these results, the
      following conclusions on the role of nonspiking interneurons in the generation of
      rhythmic motor activity, and thus potentially also during locomotion, emerge: (1)
      During rhythmic motor activity most nonspiking interneurons receive strong
      synaptic drive from central rhythm-generating networks; and (2) individual
      nonspiking interneurons some of which underlie sensory-motor pathways in posture
      control, are elements of central neuronal networks that generate alternating
      activity in antagonistic leg motoneuron pools.

PMID- 7561830
TI  - Lack of a synergistic effect between estradiol and dihydrotestosterone in the
      masculinization of the zebra finch song system.
AB  - Previous studies have suggested that both major active metabolites of
      testosterone, estradiol (E2) and dihydrotestosterone (DHT), are needed for
      complete masculinization of the brain regions that control song in passerine
      birds. However, DHT treatment of hatchling female zebra finches has only small
      masculinizing effects on the song system. To assess whether E2 and DHT have a
      synergistic effect on the masculinization of the zebra finch song system, female
      zebra finches were given Silastic implants of E2 on the day of hatching (day 1)
      either without any additional hormone treatment or in combination with DHT on
      days 1, 14, or 70. At 105 to 110 days of age, we measured the volumes of Area X,
      higher vocal center (HVC), robust nucleus of the archistriatum (RA), soma sizes
      in HVC, RA, and the lateral magnocellular nucleus of the neostriatum (IMAN), and
      neuron density and number in RA. E2 masculinized all of the measures in the song
      system with the exception of the number of neurons in RA. DHT did not synergize
      with E2 to produce any additional masculinization of the attributes measured.
      These data demonstrate that the combination of E2 and DHT did not result in the
      complete masculinization of the song control nuclei and argue against the
      importance of androgen in sexual differentiation of the song system.

PMID- 7561831
TI  - Naturally occurring motoneuron cell death in rat upper respiratory tract motor
      nuclei: a histological, fast DiI and immunocytochemical study in the hypoglossal
      nucleus.
AB  - We have previously reported on our investigation of motoneuron cell death (MCD)
      in the rat nucleus ambiguus (NA). This article focuses on the other major upper
      respiratory tract motor nucleus: the hypoglossal. The hypoglossal nucleus (XII)
      contains motoneurons to the tongue and, as such, plays a critical role in
      defining patterns of respiration, deglutition, and vocalization. Motoneuron
      counts were made in XII in a developmental series of rats. In addition, the
      neural tracer fast DiI was used to ensure that all hypoglossal motoneurons had
      migrated into the nucleus at the time cell death was assessed. Furthermore, an
      antibody to gamma-aminobutyric acid (GABA) was used to determine the potential
      effect of inadvertently counting large interneurons on motoneuron counts. Cell
      death in XII was shown to occur entirely prenatally with a loss of 35% of cells
      between embryonic day 16 (E16) and birth. Fast DiI tracings of the prenatal
      hypoglossal nerve indicated that all motoneurons were present in a well-defined
      nucleus by E15. Immunocytochemical staining for GABA demonstrated considerably
      fewer interneurons than motoneurons in XII. These findings in XII, in comparison
      with those previously reported for NA, demonstrate differences in the timing and
      amount of cell death between upper respiratory tract motor nuclei. These
      differences establish periods during which one nucleus may be preferentially
      insulted by environmental or teratogenic factors. Preferential insults may
      underlie some of the upper respiratory tract incoordination pathologies seen in
      the newborn such as the sudden infant death syndrome (SIDS).

PMID- 7561832
TI  - Regulated expression of neurofibromin in migrating neural crest cells of avian
      embryos.
AB  - Neurofibromatosis type 1 (NF1) is a common human genetic disease involving
      various neural crest (NC)-derived cell types, in particular, Schwann cells and
      melanocytes. The gene responsible for NF1 encodes the protein neurofibromin,
      which contains a domain with amino acid sequence homology to the ras-guanosine
      triphosphatase activating protein, suggesting that neurofibromin may play a role
      in intracellular signaling pathways regulating cellular proliferation or
      differentiation, or both. To determine whether neurofibromin plays a role in NC
      cell development, we used antibodies raised against human neurofibromin fusion
      proteins in western blot and immunocytochemical studies of early avian embryos.
      These antibodies specifically recognized the 235 kD chicken neurofibromin
      protein, which was expressed in migrating trunk and cranial NC cells of early
      embryos (E1.5 to E2), as well as in endothelial and smooth muscle cells of blood
      vessels and in a subpopulation of non-NC-derived cells in the dermamyotome. At
      slightly later stages (E3 to E5), neurofibromin immunostaining was observed in
      various NC derivatives, including dorsal root ganglia and peripheral nerves, as
      well as non-NC-derived cell types, including heart, skeletal muscle, and kidney.
      At still later stages (E7 to E9), neurofibromin immunoreactivity was found in
      almost all tissues in vivo. To determine whether the levels of neurofibromin
      changed during melanocyte and Schwann cell development, tissue culture
      experiments were performed. Cultured NC cells were found to express neurofibromin
      at early time points in culture, but the levels of immunoreactivity decreased as
      the cells underwent pigmentation. Schwann cells, on the other hand, continued to
      express neurofibromin in culture. These data suggest, therefore, that
      neurofibromin may play a role in the development of both NC cells and a variety
      of non-NC-derived tissues.

PMID- 7561833
TI  - Inhibition of formation of filopodia after axotomy by inhibitors of protein
      tyrosine kinases.
AB  - The activity of motile protrusions of the growth cone--filopodia, veils, and
      lamellipodia--is essential for directed growth of a neuronal process. The
      regulation of the formation of these protrusions is not well understood. Numerous
      filopodia and veils or lamellipodia form within minutes of transection of an
      Aplysia axon in culture, as the initial components of growth cones of
      regenerating neurites. Axotomy, therefore, provides a robust and reliable
      protocol for analyzing the formation of these protrusions. We evaluated the
      involvement of protein phosphorylation in the regulation of protrusive activity.
      Of the inhibitors of protein kinases assayed, only the inhibitors of protein
      tyrosine kinases--genistein, lavendustin A, herbimycin A, and erbstatin analogue-
      suppressed the formation of protrusions, as assessed by high magnification video
      microscopy. These drugs did not work by preventing resealing of the axon, as
      evident from visual inspection and by the unimpaired effectiveness of genistein
      or lavendustin in preventing formation of filopodia when applied after resealing.
      Inhibition of protein tyrosine kinases not only prevented the formation of actin
      based protrusions, but also caused deterioration of the actin network underlying
      the protrusive area of preexisting growth cones. Consistent with an involvement
      of protein tyrosine phosphorylation in the generation of protrusive structures,
      immunocytochemistry revealed that aggregates of phosphotyrosine appeared at the
      margins of the axon, from which protrusions emerge shortly after axotomy. These
      results suggest a role for protein tyrosine phosphorylation in the formation and
      maintenance of actin-based protrusive structures.

PMID- 7561834
TI  - Differential regulation of motor neuron survival and choline acetyltransferase
      expression following axotomy.
AB  - Although it is well known that motor neuron survival following axotomy is
      enhanced with maturation, the ability of surviving neurons to express the
      cholinergic enzyme choline acetyltransferase (ChAT) following axotomy has not ben
      closely examined. Moreover, the utility of the facial nucleus in studies of
      motoneuron response to injury and to trophic factors, coupled with the increasing
      importance of the mouse in gene targeting, compelled us to investigate the age
      dependence of neuronal survival and ChAT expression in the mouse facial nucleus
      following axotomy. We cut the facial nerve at postnatal day (P) 4, 7, 14, 21, and
      28 or in the adult and used Nissl staining and ChAT immunocytochemistry to
      quantitate survival and ChAT expression, respectively, following 1, 2, or 3
      weeks' survival at each age. We confirm in this model that the rate and extent of
      motor neuron death following axotomy is reduced with increasing maturity. The
      surviving neurons maintain a high ChAT content through P21; however, axotomy from
      P28 through adulthood results in a striking reduction in ChAT immunoreactivity.
      That is, although axotomy at P21 results in 61% motor neuron survival, with
      virtually all of the surviving neurons being ChAT positive, axotomy in the adult
      results in 72% survival but only 9% of the neurons are ChAT positive. Thus,
      surviving motor neurons in the adult animals are only weakly cholinergic. These
      results indicate that a change in the regulation of ChAT expression occurs
      following P21 so that cell survival and enzyme levels are uncoupled. We suggest
      that the putative factor or factors that enhances motor neuron survival in
      maturity is not capable of maintaining ChAT expression.

PMID- 7561836
TI  - Processing of the beta-amyloid precursor protein and its regulation in
      Alzheimer's disease.

PMID- 7561835
TI  - Brain-derived proteins that rescue spinal motoneurons from cell death in the
      chick embryo: comparisons with target-derived and recombinant factors.
AB  - Spinal motoneurons that normally die during early development can be rescued by a
      variety of purified growth or neurotrophic factors and target tissue extracts.
      There is also indirect evidence that brain or supraspinal afferent input may
      influence lumbar motoneuron survival during development and that this effect may
      be mediated by central nervous system-derived trophic agents. This report
      examines the biological and biochemical properties of motoneuron survival
      activity obtained from extracts of the embryonic chick brain. Treatment with an
      ammonium sulfate (25% to 75%) fraction of embryonic day 16 (E16) or E10 brain
      extracts rescued many spinal motoneurons that otherwise die during the normal
      period of cell death in vivo (E6 to E10). The same fractions also enhanced lumbar
      motoneuron survival following deafferentation. There were both similarities and
      differences between the active fractions derived from brain extracts (BEX) when
      compared with extracts derived from target muscles (MEX) or with purified
      neurotrophic factors. Survival activity from E10 BEX was as effective in
      promoting motoneuron survival as E10 MEX and more effective than astrocyte
      conditioned media. Unlike MEX, the active fractions from BEX also rescued placode
      derived nodose ganglion cells. In addition, unlike nerve growth factor and brain
      derived neurotrophic factor, active BEX fractions did not rescue neural crest
      derived dorsal root ganglion cells or sympathetic ganglion neurons.
      Interestingly, among many cranial motor and other brainstem nuclei examined, only
      the survival of motoneurons from the abducens nucleus was enhanced by BEX. Active
      proteins obtained from BEX were further separated by gel filtration
      chromatography and by preparative isoelectric focusing techniques. Activity was
      recovered in a basic (pI 8) and an acidic (pI 5) small molecular weight protein
      fraction (20 kD or less). The specific activity of the basic fraction was
      increased x66 when compared with the specific activity of crude BEX, and the
      basic fraction had a slightly higher specific activity than the acidic fraction.
      The biological and biochemical properties of these fractions are discussed in the
      context of known neurotrophic factors and their effects on normal and lesion
      induced motoneuron death during development.

PMID- 7561837
TI  - Role of phospholipase D activation in nervous system physiology and
      pathophysiology.

PMID- 7561838
TI  - Learning-induced expression of meningeal ependymin mRNA and demonstration of
      ependymin in neurons and glial cells.
AB  - The turnover of a CNS-specific cell adhesion glycoprotein, ependymin, has earlier
      been found to increase during periods of neuronal plasticity. Here, ependymin
      mRNA expression was analyzed by semiquantitative in situ hybridization in
      goldfish. Learning of an active avoidance response resulted in a significant
      increase in ependymin mRNA expression 20 min to 4 h after acquisition of the
      task. In contrast, yoked control animals that were exposed to the same numbers of
      conditioned and unconditioned stimuli in a random, unpaired manner exhibited a
      strong down-regulation of ependymin mRNA. Hybridization signals were also
      increased by injection of anti-ependymin antiserum into brain ventricles.
      Ependymin mRNA was exclusively localized to reticular-shaped fibroblasts of the
      inner endomeningeal cell layer. Immunoelectron microscopic investigation,
      however, revealed ependymin also in distinct neuronal and glial cell populations
      in which no ependymin mRNA had been detected. Uptake of meningeal protein factors
      into glial and neuronal cells may therefore be of functional importance for
      plastic adaptations of the CNS.

PMID- 7561839
TI  - Inhibition of memory consolidation after active avoidance conditioning by
      antisense intervention with ependymin gene expression.
AB  - A rapid increase in ependymin mRNA expression demonstrated by semiquantitative in
      situ hybridization after avoidance conditioning on goldfish suggested a molecular
      demand for newly synthesized ependymin translation product. To inhibit de novo
      synthesis of ependymin molecules without interference with preexisting ones, 18
      mer anti-ependymin mRNA-phosphorothioate oligodeoxynucleotides (S-ODNs) were
      injected into the perimeningeal brain fluid before active avoidance training. S
      ODN-injected animals learned the avoidance response; however, they were amnesic
      in the test. When injected into overtrained animals, S-ODNs did not interfere
      with retrieval or performance of the avoidance response. Fish treated with
      randomized S-ODN sequences served as further controls. Incorporation of S-ODNs
      was analyzed by injection of fluorescein isothiocyanate (FITC)-conjugated
      oligodeoxynucleotide probes. Microscopic observation revealed strong FITC-S-ODN
      fluorescence in reticular-shaped fibroblasts, the only known site of ependymin
      synthesis. Results demonstrate that selective inhibition of ependymin gene
      expression in vivo can specifically prevent memory formation. We conclude that in
      particular the newly synthesized ependymin molecules are involved in memory
      consolidation, possibly because they have not yet undergone irreversible
      molecular changes, which have been reported of this glycoprotein in a low-calcium
      microenvironment.

PMID- 7561840
TI  - Three unique 5' untranslated regions are spliced to common coding exons of high-
      and low-molecular-weight microtubule-associated protein-2.
AB  - Three unique 5' untranslated regions (UTRs) have been characterized for human
      microtubule-associated protein-2 (MAP-2) transcripts. All three UTRs shared a
      common 171-bp sequence adjacent to the MAP-2 coding region and then diverged
      upstream. The size of the unique upstream sequence was 281, 146, or 104 bp. PCR
      of genomic DNA demonstrated that the 5' UTRs span multiple exons. The unique
      region of the UTRs recognizes a 9.5- and a 6-kb MAP-2 transcript in poly(A)+ mRNA
      isolated from human MSN cells, and PCR analysis demonstrated that each unique UTR
      is contained in multiple high- and low-molecular-weight MAP-2 transcripts.
      Reverse transcription-PCR (RT-PCR) performed on MSN mRNA isolated from polysomes
      demonstrated that all three of the UTRs contained within multiple MAP-2
      transcripts were associated with polysomes and hence translated. RT-PCR from
      human fetal spinal cord and adult brain mRNA demonstrated that all of the UTRs
      are expressed at these developmental time points.

PMID- 7561843
TI  - Light-induced CREB phosphorylation and gene expression in rat retinal cells.
AB  - The signal pathway for light-induced expression of c-fos and the neuropeptide
      somatostatin (SS) in rat retinal cells was investigated. Flashing light induced c
      fos and SS mRNA in the inner nuclear layer and the ganglion cell layer. As both c
      fos and SS genes have a cyclic AMP response element (CRE) in their promoters, CRE
      binding protein (CREB) phosphorylation in retinal cells was examined with a
      phospho-CREB-specific antibody. Both flashing light and administration of the L
      type Ca2+ channel activator Bay K 8644 induced phosphorylation of CREB in the
      nuclei of the amacrine cells and the ganglion cells where c-fos/SS mRNAs were
      expressed. These cells could be double-stained with anti-calmodulin kinase II
      (anti-CaM kinase II) monoclonal antibody and phospho-CREB-specific polyclonal
      antiserum after Bay K 8644 administration, indicating the colocalization of
      phosphorylated CREB at Ser133 and CaM kinase II in the neural retina.

PMID- 7561841
TI  - Dynorphins modulate DNA synthesis in fetal brain cell aggregates.
AB  - Previously, opioid peptide analogues, beta-endorphin, and synthetic opiates were
      found to inhibit DNA synthesis in 7-day fetal rat brain cell aggregates via kappa
      and mu-opioid receptors. Here dynorphins and other endogenous opioid peptides
      were investigated for their effect on DNA synthesis in rat and guinea pig brain
      cell aggregates. At 1 microM, all dynorphins tested and beta-endorphin inhibited
      [3H]thymidine incorporation into DNA by 20-38% in 7-day rat brain cell
      aggregates. The putative epsilon-antagonist beta-endorphin (1-27) did not prevent
      the effect of beta-endorphin, suggesting that the epsilon-receptor is not
      involved in opioid inhibition of DNA synthesis. The kappa-selective antagonist
      norbinaltorphimine blocked dynorphin A or B inhibition of DNA synthesis,
      implicating a kappa-opioid receptor. In dose-dependency studies, dynorphin B was
      three orders of magnitude more potent than dynorphin A in the attenuation of
      thymidine incorporation, indicative of the mediation of its action by a discrete
      kappa-receptor subtype. The IC50 value of 0.1 nM estimated for dynorphin B is in
      the physiological range for dynorphins in developing brain. In guinea pig brain
      cell aggregates, the kappa-receptor agonists U50488, U69593, and dynorphin B
      reduced thymidine incorporation by 40%. When 21-day aggregates were treated with
      dynorphins, a 33-86% enhancement of thymidine incorporation was observed. Because
      both 7- and 21-day aggregates correspond to stages in development when glial cell
      proliferation is prevalent and glia preferentially express kappa-receptors in rat
      brain, these findings support the hypothesis that dynorphins modulate glial DNA
      synthesis during brain ontogeny.

PMID- 7561844
TI  - Staurosporine induces astrocytic phenotypes and differential expression of
      specific PKC isoforms in C6 glial cells.
AB  - In this study we examined the effects of staurosporine, a potent inhibitor of
      protein kinase C (PKC), on the differentiation of C6 glial cells and on the
      expression and cellular distribution of specific PKC isoforms. Staurosporine
      reduced cell proliferation and induced distinctive changes in the morphological
      appearance of the cells to that characteristic of cells exhibiting astrocytic
      phenotypes. The differentiative effect of staurosporine was further indicated by
      the increased expression of two proteins related to astrocytic phenotypes, glial
      fibrillary acidic protein (GFAP) and glutamine synthetase. Thus, staurosporine
      induced a dose-dependent increase both in GFAP immunoreactivity and in the
      activity and protein levels of glutamine synthetase. Staurosporine also induced a
      decrease in the expression of PKC-beta 2 and an increase in that of PKC-gamma. In
      addition, it induced translocation of PKC-epsilon from the membrane to the
      cytosol, whereas no differences were observed in the distribution of the other
      PKC isoforms. The results of our study indicate that staurosporine induced
      astrocytic phenotypes in glial cells and that changes in the expression and
      cellular distribution of these PKC isoforms may be related to astrocytic
      differentiation.

PMID- 7561845
TI  - Adenosine receptors modulate [Ca2+]i in hippocampal astrocytes in situ.
AB  - Cultured astroglia express both adenosine and ATP purinergic receptors that are
      coupled to increases in intracellular calcium concentration ([Ca2+]i). Currently,
      there is little evidence that such purinergic receptors exist on astrocytes in
      vivo. To address this issue, calcium-sensitive fluorescent dyes were used in
      conjunction with confocal microscopy and immunocytochemistry to examine the
      responsiveness of astrocytes in acutely isolated hippocampal slices to purinergic
      neuroligands. Both ATP and adenosine induced dynamic increases in astrocytic
      [Ca2+]i that were blocked by the adenosine receptor antagonist 8-(p
      sulfophenyl)theophylline. The responses to adenosine were not blocked by
      tetrodotoxin, 8-cyclopentyltheophylline, 8-(3-chlorostyryl)caffeine,
      dipyridamole, or removal of extracellular calcium. The P2Y-selective agonist 2
      methylthioadenosine triphosphate was unable to induce increases in astrocytic
      [Ca2+]i, whereas the P2 agonist adenosine 5'-O-(2-thiodiphosphate) induced
      astrocytic responses in a low percentage of astrocytes. These results indicate
      that the majority of hippocampal astrocytes in situ contain P1 purinergic
      receptors coupled to increases in [Ca2+]i, whereas a small minority appear to
      contain P2 purinergic receptors. Furthermore, individual hippocampal astrocytes
      responded to adenosine, glutamate, and depolarization with increases in [Ca2+]i.
      The existence of both purinergic and glutamatergic receptors on individual
      astrocytes in situ suggests that astrocytes in vivo are able to integrate
      information derived from glutamate and adenosine receptor stimulation.

PMID- 7561842
TI  - Differential induction of immediate early gene proteins in cultured neurons by
      beta-amyloid (A beta): association of c-Jun with A beta-induced apoptosis.
AB  - beta-Amyloid (A beta) is a 39-42 amino acid that is the primary component of
      plaques in Alzheimer's disease (AD). Previous studies from our laboratory and
      others have shown that A beta induces neurodegeneration via apoptosis in vitro,
      suggesting that A beta may also initiate an apoptotic pathway of cell death in
      AD. Apoptosis has been suggested to proceed by a gene-directed program in several
      systems. Accordingly, we have investigated whether A beta-mediated apoptosis is
      associated with the induction of genes that may regulate or play a role in cell
      death in vitro. Immediate early genes (IEGs) respond to cellular stimuli and
      participate in cellular signaling pathways. The protein products of some IEGs,
      e.g., c-jun, are capable of forming dimers and acting as transcriptional
      regulatory proteins, and have been implicated in apoptosis in both nonneuronal
      and neuronal cells. In this study, we report a selective and abnormally sustained
      induction of c-Jun in cultured hippocampal neurons treated with A beta. In
      addition, we describe the lack of induction of c-Jun in neurons that are
      relatively resistant to A beta-mediated toxicity, and a correspondence between
      immunoreactivity for c-Jun and changes in nuclear morphology that are indicative
      of apoptosis. These data demonstrate that c-Jun is induced in cultured neurons
      that undergo A beta-mediated apoptosis and suggest that c-Jun may participate in
      a cell death program in these neurons.

PMID- 7561846
TI  - Components of the plasminogen activator system in astrocytes are modulated by
      tumor necrosis factor-alpha and interleukin-1 beta through similar signal
      transduction pathways.
AB  - Migration of astrocytes is thought to play a role in nerve regeneration and to be
      mediated, at least in part, by inflammation-associated cytokines. Plasminogen
      activators are secreted proteases that function in fibrinolysis and participate
      in cellular migration and invasion and, in some cases, are modulated by
      cytokines. Here, we show that two cytokines, tumor necrosis factor-alpha and
      interleukin-1 beta, can modulate plasminogen activation in astrocytes, each
      causing 90% reduction of total plasminogen activator activity. Direct and reverse
      zymography indicated that this reduction resulted from two simultaneous events, a
      pronounced decrease in tissue-type plasminogen activator activity and an
      induction of plasminogen activator inhibitor-1. Northern hybridization analysis
      indicated a 30-fold increase of the steady-state level of plasminogen activator
      inhibitor-1 mRNA following treatment with each of the two cytokines. Both of the
      cytokine-induced effects could be blocked by cycloheximide or actinomycin D. When
      signal transduction pathways were blocked, the results indicated the involvement
      of reduction in cyclic AMP levels, protein kinase activity, and arachidonic
      metabolites of the lipoxygenase pathway. The results thus show that the two
      cytokines reduce the ability of astrocytes to conduct fibrinolysis and
      extracellular proteolysis, and suggest that the effect of these cytokines on
      members of the plasminogen activation system is through a common signal
      transduction pathway.

PMID- 7561847
TI  - The expression of two splice variants of metabotropic glutamate receptor subtype
      5 in the rat brain and neuronal cells during development.
AB  - We previously reported that a variant with extra amino acid residues exists in
      the metabotropic glutamate receptor subtype 5 (mGluR5). Either of the two
      isoforms, named mGluR5b and mGluR5a for the isoforms with and without the
      inserted sequence, respectively, generated Ca(2+)-activated Cl- current when
      expressed in Xenopus oocytes. We herein report that these two isoforms are
      produced by the alternative splicing of the exon skipping type. When examined
      during the course of postnatal development, the major mGluR5 isotype mRNA was
      observed to switch from mGluR5a to mGluR5b in the rat hippocampus and the
      cerebral cortex. We also investigated two cell lines that could be differentiated
      into neuron-like cells in vitro. Whereas the mGluR5b mRNA was hardly detectable
      in either undifferentiated or differentiated NG108-15 cells, the relative amounts
      of the two variant mRNAs changed after the induction of differentiation in the
      P19 cells. An extracellular application of trans-D,L-1-amino-1,3
      cyclopentanedicarboxylate on the neuron-like P19 cells induced intracellular Ca2+
      mobilization, thus suggesting that the cells could express functional mGluR(s)
      coupled to phospholipase C and other components that could mediate the signal
      transduction pathway. This cell line may thus provide a model system for studying
      both mGluR5 expression and other mGluR-induced phenomena at the molecular level.

PMID- 7561851
TI  - Evidence that the modulation of membrane-associated protein kinase C activity by
      an endogenous inhibitor plays a role in N1E-115 murine neuroblastoma cell
      differentiation.
AB  - Murine neuroblastoma cells, N1E-115, were induced to differentiate into neuron
      like cells by serum deprivation for 18 h. As previous studies have shown that the
      suppression of protein kinase C (PKC) activity by selective inhibitors or
      neutralizing antibodies induces neuroblastoma cells to differentiate, we tested
      the hypothesis that serum deprivation may cause a rapid loss in membrane PKC
      activity that occurs well before the morphological changes that are
      characteristic of cell differentiation. A significant reduction in particulate
      (membrane) PKC activity was indeed observed within 3 h of serum withdrawal when
      enzyme activity was measured in intact native membranes by the recently described
      in vitro "direct" assay. This rapid reduction in enzyme activity was confirmed by
      the decreased phosphorylation of the MARCKS protein, an endogenous PKC-selective
      substrate, in intact cells. The decrease in membrane PKC activity occurred
      without any loss in the amount of membrane-associated enzyme, suggesting that
      some factor(s) resident in neuroblastoma membranes was suppressing PKC activity.
      Indeed, results indicate the presence of an endogenous inhibitor of PKC tightly
      associated with neuroblastoma membranes. This inhibitory activity increased in
      the membranes of cells subjected to serum deprivation, raising the possibility
      that it was likely responsible for the decline in membrane PKC activity in
      differentiating N1E-115 cells. Preliminary characterization indicated that the
      inhibitory activity is a protein and is localized mainly in the membrane
      fraction. Thus, these results demonstrate directly that endogenous inhibitor can
      regulate membrane-associated PKC activity in cells and thereby modulate PKC
      related neuronal functions.

PMID- 7561849
TI  - Sphingolipid biosynthesis is necessary for dendrite growth and survival of
      cerebellar Purkinje cells in culture.
AB  - The requirement of complex sphingolipid biosynthesis for growth of neurons was
      examined in developing rat cerebellar Purkinje neurons using a dissociated
      culture system. Purkinje cells developed well-differentiated dendrites and axons
      after 2 weeks in a serum-free nutrient condition. Addition of 2 microM fumonisin
      B1, a fungal inhibitor of mammalian ceramide synthase, inhibited incorporation of
      [3H]galactose/glucosamine and [14C]-serine into complex sphingolipids of cultured
      cerebellar neurons. Under this condition, the expression of Purkinje cell
      enriched sphingolipids, including GD1 alpha, 9-O-acetylated LD1 and GD3, and
      sphingomyelin, was significantly decreased. After 2 weeks' exposure to fumonisin
      B1, dose-dependent measurable decreases in the survival and visually discernible
      differences in the morphology were seen in fumonisin-treated Purkinje cells. The
      Purkinje cell dendrites exhibited two types of anomalies; one population of cells
      developed elongated but less-branched dendrites after a slight time lag, but
      their branches began to degenerate. In some cells, formation of elongated
      dendrite trees was severely impaired. However, treatment with fumonisin B1 also
      led to the formation of spinelike protrusions on the dendrites of Purkinje cells
      as in control cultures. In contrast to the alterations observed in Purkinje
      cells, morphology of other cell types including granule neurons appeared to be
      almost normal after treatment with fumonisin B1. These observations indicated
      strongly that membrane sphingolipids participate in growth and maintenance of
      dendrites and in the survival of cerebellar Purkinje cells. Indeed, these effects
      of fumonisin B1 were reversed, but not completely, by the addition of 6-[[N-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)-amino dcaproyl]sphingosine (C6-NBD-ceramide), a
      synthetic derivative of ceramide. Thus, we conclude that deprivation of membrane
      sphingolipids in a culture environment is responsible for aberrant growth of
      Purkinje cells.

PMID- 7561848
TI  - Peroxynitrite-induced cytotoxicity in PC12 cells: evidence for an apoptotic
      mechanism differentially modulated by neurotrophic factors.
AB  - Peroxynitrite is a powerful oxidant formed by the near-diffusion-limited reaction
      of nitric oxide with superoxide. Large doses of peroxynitrite (> 2 mM) resulted
      in rapid cell swelling and necrosis of undifferentiated PC12 cells. However,
      brief exposure to lower concentrations of peroxynitrite (EC50 = 850 microM)
      intially (3-4 h) caused minimal damage to low-density cultures. By 8 h,
      cytoplasmic shrinkage with nuclear condensation and fragmentation became
      increasingly evident. After 24 h, 36% of peroxynitrite-treated cells demonstrated
      these features associated with apoptosis. In addition, 46% of peroxynitrite
      treated cells demonstrated DNA fragmentation (by terminal-deoxynucleotide
      transferase-mediated dUTP-digoxigenin nick end-labeling) after 7 h, which was
      inhibited by posttreatment with the endonuclease inhibitor aurintricarboxylic
      acid. Serum starvation also resulted in apoptosis in control cells (23%), the
      percentage of which was not altered significantly by peroxynitrite treatment.
      Although peroxynitrite is known to be toxic to cells, the present study provides
      a first indication that peroxynitrite induces apoptosis. Furthermore,
      pretreatment of cells with nerve growth factor or insulin, but not epidermal
      growth factor, was protective against peroxynitrite-induced apoptosis. However,
      both acidic and basic fibroblast growth factors greatly increased peroxynitrite
      initiated apoptosis, to 63 and 70%, respectively. Thus, specific trophic factors
      demonstrate differential regulation of peroxynitrite-induced apoptosis in vitro.

PMID- 7561850
TI  - Metallothionein induction in neonatal rat primary astrocyte cultures protects
      against methylmercury cytotoxicity.
AB  - Metallothionein (MT) protein and mRNA levels were monitored following exposure of
      rat neonatal primary astrocyte cultures to methylmercury (MeHg). MT-I and MT-II
      mRNAs were probed on northern blots with an [alpha-32P]dCTP-labeled synthetic
      cDNA probe specific for rat MT mRNA. MT-I and MT-II mRNAs were detected in
      untreated cells, suggesting constitutive MT expression in these cells. The probes
      hybridize to a single mRNA with a size appropriate for MT, approximately 550 and
      350 bp for MT-I and MT-II, respectively. Expression of MT-I and MT-II mRNA in
      astrocyte monolayers exposed to 2 x 10(-6) M MeHg for 6 h was increased over MT-I
      and MT-II mRNA levels in controls. Western blot analysis revealed a time
      dependent increase in MT protein synthesis through 96 h of exposure to MeHg.
      Consistent with the constitutive expression of MTs at both the mRNA level and the
      protein level, we have also demonstrated a time-dependent increase in MT
      immunoreactivity in astrocytes exposed to MeHg. The cytotoxic effects of MeHg
      were measured by the rate of astrocytic D-[3H]aspartate uptake. Preexposure of
      astrocytes to CdCl2, a potent inducer of MTs, completely reversed the inhibitory
      effect of MeHg on D-[3H]aspartate uptake that occurs in MeHg-treated astrocytes
      with constitutive MT levels. Associated with CdCl2 treatment was a time-dependent
      increase in astrocytic MT levels. In summary, astrocytes constitutively express
      MTs; treatment with MeHg increases astrocytic MT expression, and increased MT
      levels (by means of CdCl2 pretreatment) attenuate MeHg-induced toxicity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7561854
TI  - Potentiation of agonist-stimulated cyclic AMP accumulation by tyrosine kinase
      inhibitors in rat pinealocytes.
AB  - To study cross-talk mechanisms in rat pinealocytes, the role of tyrosine kinase
      or kinases in the regulation of adrenergic-stimulated cyclic AMP production was
      investigated. Both norepinephrine- and isoproterenol-stimulated cyclic AMP
      accumulation were increased by two distinct tyrosine kinase inhibitors, genistein
      or erbstatin, in a concentration-dependent manner. A similar increase was
      observed with two other inhibitors, tyrphostin B44 and herbimycin. In contrast,
      daidzein, an inactive analogue of genistein, was ineffective; whereas vanadate, a
      phosphotyrosine phosphatase inhibitor, reduced the adrenergic-stimulated cyclic
      AMP accumulation. The tyrosine kinase inhibitors were effective in potentiating
      the cholera toxin-or forskolin-stimulated cyclic AMP accumulation, indicating
      that their sites of action are at the postreceptor level. Neither an activator
      nor inhibitors of protein kinase C influenced the potentiation of the cyclic AMP
      responses by genistein, suggesting that the potentiation effect by tyrosine
      kinase inhibitors does not involve the phospholipase C/protein kinase C pathway.
      However, when the phosphodiesterase was inhibited by isobutylmethylxanthine,
      genistein failed to potentiate and vanadate did not inhibit the adrenergic
      stimulated cyclic AMP accumulation, indicating that the phosphodiesterase is a
      probable site of action for these inhibitors. These results suggest that cyclic
      AMP metabolism in the pinealocytes is tonically inhibited by tyrosine kinase
      acting on the cyclic AMP phosphodiesterase.

PMID- 7561853
TI  - Endothelin 1 stimulates Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport through
      ETA receptors and protein kinase C-dependent pathway in cerebral capillary
      endothelium.
AB  - The effect of endothelins (ET-1 and ET-3) on 86Rb+ uptake as a measure of K+
      uptake was investigated in cultured rat brain capillary endothelium. ET-1 or ET-3
      dose-dependently enhanced K+ uptake (EC50 = 0.60 +/- 0.15 and 21.5 +/- 4.1 nM,
      respectively), which was inhibited by the selective ETA receptor antagonist BQ
      123 (cyclo-D-Trp-D-Asp-Pro-D-Val-Leu). Neither the selective ETB agonists IRL
      1620 [N-succinyl-(Glu9,-Ala11,15)-ET-1] and sarafotoxin S6c, nor the ETB receptor
      antagonist IRL 1038 [(Cys11,Cys15)-ET-1] had any effect on K+ uptake. Ouabain
      (inhibitor of Na+,K(+)-ATPase) and bumetanide (inhibitor of Na(+)-K(+)-Cl-
      cotransport) reduced (up to 40% and up to 70%, respectively) the ET-1-stimulated
      K+ uptake. Complete inhibition was seen with both agents. Phorbol 12-myristate 13
      acetate (PMA), activator of protein kinase C (PKC), stimulated Na+,K(+)-ATPase
      and Na(+)-K(+)-Cl- cotransport. ET-1- but not PMA-stimulated K+ uptake was
      inhibited by 5-(N-ethyl-N-isopropyl)amiloride (inhibitor of Na+/H+ exchange
      system), suggesting a linkage of Na+/H+ exchange with ET-1-stimulated Na+,K(+)
      ATPase and Na(+)-K(+)-Cl- cotransport activity that is not mediated by PKC.

PMID- 7561852
TI  - Rat frontal cortex beta 1-adrenoceptors are activated by the beta 3-adrenoceptor
      agonists SR 58611A and SR 58878A but not by BRL 37344 or ICI 215,001.
AB  - SR 58611A, a selective agonist of gut and brown adipose tissue beta 3
      adrenoceptors (beta 3 ARs), has been reported to have antidepressant-like
      activity in rodents, by indicating brain beta 3ARs as the sites of this property.
      SR 58611A and its acid metabolite SR 58878A, as opposed to BRL 37344, ICI
      215,001, and CGP 12177, increased cyclic AMP levels in rat frontal cortex. ICI
      215,001, differently from BRL 37344, at concentrations in the millimolar range
      antagonized norepinephrine- or (-)-isoproterenol-stimulated adenylyl cyclase
      partially. The increase of cyclic AMP levels induced by SR 58878A was blocked
      selectively by beta 1AR antagonist CGP 20712A but not by beta 2AR antagonist ICI
      118,551. In addition, PCR analysis did not reveal beta 3AR mRNA, and no specific
      beta 3AR binding sites were detected by [3H]CGP 12177 in rat frontal cortex. When
      down-regulation of the beta 1AR ligand binding and mRNA levels had been induced
      in frontal cortex by chronic administration of imipramine, SR 58878A as well as
      norepinephrine and (-)-isoproterenol inceased the cyclic AMP production less
      markedly. Our findings indicate that beta 3ARs are absent in the adult rat
      frontal cortex, and that various beta 3AR agonists differently affect the frontal
      cortex beta 1ARs, indicating that SR 58611A may exert its putative antidepressant
      effect acting on the frontal cortex beta 1ARS.

PMID- 7561855
TI  - Evidence for presynaptic adenosine A2a receptors associated with norepinephrine
      release and their desensitization in the rat nucleus tractus solitarius.
AB  - Rat medullary brain segments containing primarily nucleus tractus solitarius
      (NTS) were used for superfusion studies of evoked transmitter release and for
      isotherm receptor binding assays. Isotherm binding assays with [3H]CGS-21680 on
      membranes prepared from NTS tissue blocks indicated a single high-affinity
      binding site with a KD of 5.1 +/- 1.4 nM and a Bmax of 20.6 +/- 2.4 fmol/mg of
      protein. The binding density for [3H]CGS-21680 on NTS membranes was 23 times less
      than comparable binding on membranes from striatal tissue. Electrically
      stimulated (1 min at 25 mA, 2 ms, 3 Hz) release of [3H]norepinephrine ([3H]NE)
      from 400-microns-thick NTS tissue slices resulted in an S2/S1 ratio of 0.96 +/-
      0.02. Superfusion of single tissue slices with 0.1-100 nM CGS-21680, a selective
      adenosine A2a receptor agonist, for 5 min before the S2 stimulus produced a
      significant concentration-dependent increase in the S2/S1 fractional release
      ratio that was maximal (31.3% increase) at 1.0 nM. However, superfusion of tissue
      slices with CGS-21680 over the same concentration range for 20 min before the S2
      stimulus did not alter the S2/S1 ratio significantly from control release ratios.
      The augmented release of [3H]NE mediated by 1.0 nM CGS-21680 with a 5-min tissue
      exposure was abolished by 1.0 and 10 nM CGS-15943 as well as by 100 nM 8-(3
      chlorostyryl)caffeine, both A2a receptor antagonists, but not by 1.0 nM 8
      cyclopentyl-1,3-dipropylxanthine, the A1 receptor antagonist.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7561856
TI  - Opioid-induced increase in [Ca2+]i in ND8-47 neuroblastoma x dorsal root ganglion
      hybrid cells is mediated through G protein-coupled delta-opioid receptors and
      desensitized by chronic exposure to opioid.
AB  - delta-Receptor agonists induce a concentration-dependent increase in
      intracellular calcium concentration ([Ca2+]i) in ND8-47 cells by activating
      dihydropyridine-sensitive Ca2+ channels. The role of G proteins in transducing
      the opioid effect has been studied. Pretreatment of cells with pertussis toxin
      (100 ng/ml, 24 h) almost completely blocked [D-Ser2,Leu5]enkephalin-Thr (DSLET)
      induced increase in [Ca2+]i. Cholera toxin (10 nM, 24 h) had no effect on DSLET
      induced response. Pretreatment of the cells with 1 microM DSLET for 1 h resulted
      in a 30% inhibition of DSLET-induced increase in [Ca2+]i and a 78% inhibition
      after exposure for 24 h. After 1 h of exposure to DSLET, there was a decrease in
      agonist affinity with no significant changes in receptor density. Cells exposed
      to 1 microM DSLET for 24 h demonstrate a nearly 90% decrease in [3H]diprenorphine
      binding, with a decrease in affinity for agonist at the remaining binding sites.
      G protein subunits alpha i2, alpha i3, alpha s, and alpha q were detected in ND8
      47 cell membranes by western blot; alpha o and alpha i1 were not present. Chronic
      DSLET treatment had no significant effect on the quantity of each of the alpha
      subunits. These results suggest that the DSLET-induced increase in [Ca2+]i
      mediated through pertussis toxin-sensitive G proteins (probably Gi2 or Gi3) and
      the attenuation of this response in chronically treated cells is associated with
      a relatively rapid reduction in receptor affinity to DSLET and a slow reduction
      in receptor density.

PMID- 7561857
TI  - Dopamine receptor stimulation decreases cytosolic gamma protein kinase C
      immunoreactivity in rat hippocampal slices: evidence for increased Ca(2+)
      dependent proteolysis.
AB  - The effect of dopamine (DA) receptor stimulation on the distribution of gamma
      protein kinase C (gamma PKC) in hippocampal slices was assessed. Nanomolar
      concentrations of DA decreased cytosolic gamma PKC (56%) without altering
      membrane gamma PKC levels, resulting in decreased total gamma PKC
      immunoreactivity. The maximal decrease in cytosolic gamma PKC occurred at 20 min
      of incubation and was significantly blocked by the D1 DA antagonist SCH 23390
      (10(-6) M) but not by the D2 antagonist sulpiride (10(-5) M). The D1 agonists SKF
      38393 and A 77636 mimicked the effect of DA with similar responses produced at 10
      microM and 1 nM, respectively. The D2 agonist quinpirole had no effect on gamma
      PKC immunoreactivity, thus indicating that this dopaminergic response is mediated
      through a D1-like receptor. DA had no effect on alpha, delta, or zeta PKC isozyme
      immunoreactivity in the same hippocampal preparations. The DA-induced decrease in
      cytosolic gamma PKC immunoreactivity was blocked by the Ca(2+)-dependent protease
      inhibitor N-acetyl-Leu-Leu-norleucinal (100 microM) and by the inorganic Ca2+
      channel blocker Co2+. The data suggest that DA stimulates a D1-like DA receptor,
      which increases the influx of Ca2+ and activates the Ca(2+)-dependent proteolysis
      of gamma PKC.

PMID- 7561858
TI  - Low level lead exposure decreases in vivo release of dopamine in the rat nucleus
      accumbens: a microdialysis study.
AB  - The basal and K(+)-induced release of dopamine and its metabolites, 3,4
      dihydroxyphenylacetic acid and homovanillic acid, were measured in microdialysate
      samples obtained in vivo from the nucleus accumbens region of rat subchronically
      exposed to 50 ppm lead for 90 days. The basal and stimulus-induced release of
      dopamine and the metabolites were significantly reduced in the lead-exposed rats
      as compared with the controls. These reductions in dopamine and its metabolites
      are consistent with the reports of decreased dopamine availability associated
      with lead-induced changes in certain behavioral indices (fixed-interval
      performance) in rats. Furthermore, these changes were observed at blood lead
      levels similar to those considered to cause impairment in cognitive functions in
      children.

PMID- 7561859
TI  - Phosphorylation and agonist-specific intracellular trafficking of an epitope
      tagged mu-opioid receptor expressed in HEK 293 cells.
AB  - We expressed the cloned mu-opioid receptor (muR) in high abundance (5.5 x 10(6)
      sites/cell) with an amino-terminal epitope tag (EYMPME) in human embryonic kidney
      293 cells. The epitope-tagged receptor (EE-muR) was similar to the untagged mu R
      ligand binding and agonist-dependent inhibition of cyclic AMP accumulation. By
      confocal microscopy, the labeled receptor was shown to be largely confined to the
      plasma membrane. Pretreatment with morphine failed to affect the cellular
      distribution of the receptor as judged by immunofluorescence and tracer binding
      studies. In contrast, exposure to the mu-specific peptide agonist [D-Ala2,
      MePhe4, Gly-ol5]enkephalin (DAMGO) caused strong labeling of endocytic vesicles,
      indicating extensive agonist-induced cellular redistribution of EE-muR. Tracer
      binding studies suggested partial net internalization and a small degree of down
      regulation caused by DAMGO. EE-muR-containing membranes were solubilized in
      detergent [3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate] and
      immunoprecipitated by an anti-epitope monoclonal antibody. Immunoblotting
      revealed a prominent band at approximately 70 kDa with weaker bands at
      approximately 65 kDa. EE-muR was labeled with [gamma-32P]ATP in permeabilized
      cells, immunoprecipitated, and analyzed by polyacrylamide gel electrophoresis
      autoradiography. A prominent band at 65-70 kDa indicated the presence of basal
      receptor phosphorylation occurring in the absence of agonist, which was enhanced
      approximately 1.8-fold with the addition of morphine. In conclusion,
      intracellular trafficking of the muR appears to depend on the agonist, with
      morphine and DAMGO having markedly different effects. Unlike other G protein
      coupled receptors, basal phosphorylation is substantial, even in the absence of
      agonist.

PMID- 7561860
TI  - Neuropeptide Y in frontal cortex is not altered in major depression.
AB  - Previously, we reported a modest but significant reduction in the concentration
      of neuropeptide Y in frontal cortices from victims of suicide relative to age
      matched natural or accidental death control subjects. The reduction in
      neuropeptide Y appeared to be greatest in a subgroup of victims of suicide for
      which there was indirect evidence of histories of depression. We pursued these
      initial findings in the present study by measuring neuropeptide Y concentrations
      in frontal cortices from natural or accidental death control subjects and from
      suicide victims in whom a firm diagnosis of major depression was established by
      psychiatric autopsy. Because several subjects with major depression had a
      comorbid diagnosis of alcoholism, a group of victims of suicide that had an Axis
      I diagnosis of alcohol dependence was also studied. No significant differences in
      neuropeptide Y concentrations were observed between control subjects and victims
      of suicide with major depression or victims of suicide with alcohol dependence.
      These findings do not support a role for neuropeptide Y in major depression.

PMID- 7561861
TI  - Acute stimulatory effect of estradiol on striatal dopamine synthesis.
AB  - The acute effect of physiological doses of estradiol (E2) on the dopaminergic
      activity in the striatum was studied. In a first series of experiments,
      ovariectomized rats were injected with 17 alpha or 17 beta E2 (125, 250, or 500
      ng/kg of body weight, s.c.), and in situ tyrosine hydroxylase (TH) activity
      (determined by DOPA accumulation in the striatum after intraperitoneal
      administration of NSD 1015) was quantified. A dose-dependent increase in striatal
      TH activity was observed within minutes after 17 beta (but not 17 alpha) E2
      treatment. To examine whether E2 acts directly on the striatum, in a second
      series of experiments, anesthetized rats were implanted in the striatum with a
      push-pull cannula supplied with an artificial CSF containing [3H]tyrosine. The
      extracellular concentrations of total and tritiated dopamine (DA) and 3,4
      dihydroxyphenylacetic acid (DOPAC) were measured at 20-min intervals. Addition of
      10(-9) M 17 beta (but not 17 alpha) E2 to the superfusing fluid immediately
      evoked an approximately 50% increase in [3H]DA and [3H]DOPAC extracellular
      concentrations, but total DA and DOPAC concentrations remained constant. This
      selective increase in the newly synthesized DA and DOPAC release suggested that
      E2 affects DA synthesis rather than DA release. Finally, to determine whether
      this rapid E2-induced stimulation of DA synthesis was a consequence of an
      increase in TH level of phosphorylation, the enzyme constant of inhibition by DA
      (Ki(DA)) was calculated. Incubation of striatal slices in the presence of 10(-9)
      M 17 beta (but not 17 alpha) E2 indeed evoked an approximate twofold increase in
      the Ki(DA) of one form of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561862
TI  - Tau protein from Alzheimer's disease patients is glycated at its tubulin-binding
      domain.
AB  - Glycated residues of tau protein from paired helical filaments isolated from the
      brains of Alzheimer's disease patients were localized by doing a proteolytic
      cleavage of the protein, fractionation of the resulting peptides, and
      identification of those peptides using specific antibodies. The most suitable
      residues for glycation, lysines, present at the tubulin-binding motif of tau
      protein, seem to be preferentially modified compared with those lysines present
      at other regions. Among these modified lysines, those located in the sequence
      comprising residues 318-336 (in the largest human tau isoform) were found to be
      glycated, as determined by the reaction with an antibody that recognizes a
      glycated peptide containing this sequence. Because those lysines are present in a
      tubulin binding motif of tau protein, its modification could result in a decrease
      in the interaction of tau with tubulin.

PMID- 7561863
TI  - Sphingolipid metabolic disorders in Trembler mouse peripheral nerves in vivo
      result from an abnormal substrate supply.
AB  - Sphingolipid metabolic pathways in the peripheral nerves of dysmyelinating
      Trembler mice were studied in vivo, using intraneurally injected [3H]palmitate as
      the exogenous substrate. The kinetic analysis of the experimental data obtained
      for the mutant revealed that, as in normal nerves, two metabolically and
      kinetically independent pathways are implicated in the biosynthesis of the major
      peripheral nerve sphingolipids: the ceramide pathway and another pathway in which
      there is no detectable labeled intermediate ("direct amidification"). The results
      also show that, in the Trembler mouse sciatic nerves: (a) The severely deficient
      sphingolipid biosynthesis results from the constitution of a qualitatively and
      quantitatively abnormal fatty acid substrate pool destined for metabolism via the
      ceramide pathway, which ensures the totality of the galactocerebroside labeling
      and two-thirds of that of sphingomyelin. The ceramide intermediates of this
      pathway are labeled only on their fatty acyl moiety, which contains only 16
      carbon atom chains. (b) "Direct amidification" events implicated in sphingolipid
      labeling are decreased compared with normal and account for the remaining
      sphingomyelin formation.

PMID- 7561864
TI  - Extracellular GABA in the ventrolateral thalamus of rats exhibiting spontaneous
      absence epilepsy: a microdialysis study.
AB  - There is compelling evidence that excessive GABA-mediated inhibition may underlie
      the abnormal electrical activity, initiated in the thalamus, associated with
      epileptic absence seizures. In particular, the GABAB receptor subtype seems to
      play a critical role, because its antagonists are potent inhibitors of absence
      seizures, whereas its agonists exacerbate seizure activity. Using a validated rat
      model of absence epilepsy, we have previously found no evidence of abnormal GABAB
      receptor density or affinity in thalamic tissue. In the present study, we have
      used in vivo microdialysis to monitor changes in levels of extracellular GABA and
      other amino acids in this brain region. We have shown that basal extracellular
      levels of GABA and, to a lesser extent, taurine are increased when compared with
      values in nonepileptic controls. However, modifying GABAergic transmission with
      the GABAB agonist (-)-baclofen (2 mg/kg i.p.), the GABAB antagonist CGP-35348
      (200 mg/kg i.p.), or the GABA uptake inhibitor tiagabine (100 microM) did not
      produce any further alteration in extracellular GABA levels, despite the ability
      of these compounds to increase (baclofen and tiagabine) or decrease (CGP-35348)
      seizure activity. These findings suggest that the increased basal GABA levels
      observed in this animal model are not simply a consequence of seizure activity
      but may contribute to the initiation of absence seizures.

PMID- 7561865
TI  - Toxic NMDA-receptor activation occurs during recovery in a tissue culture model
      of ischemia.
AB  - In some animal models of reversible ischemia, there is a therapeutic window
      during early recovery when glutamate receptor antagonists can rescue neurons from
      injury. We have previously reported that organotypic cultures of the hippocampus
      can be protected by NMDA-receptor antagonists during recovery from a brief period
      of simulated ischemia. To model ischemia, we have used potassium cyanide to
      inhibit oxidative metabolism and 2-deoxyglucose to inhibit glycolysis. To study
      the time course and mechanisms of delayed NMDA-receptor toxicity in more detail,
      we have extended these studies to dissociated cortical cultures. Injury was
      assessed by release of lactate dehydrogenase into the culture medium. Metabolic
      inhibition for 15 min caused dose-dependent injury. Morphologic signs of neuronal
      toxicity were delayed until the recovery period. MK-801 reduced injury
      significantly when present throughout the experiment. Surprisingly, MK-801
      provided the same protection when administration was delayed until after the end
      of the metabolic inhibition, blocking NMDA receptors only during recovery. To
      examine NMDA toxicity during metabolic inhibition, the competitive NMDA-receptor
      antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid was added during
      exposure. The protective effect of NMDA-receptor blockade was completely lost if
      the antagonist was removed during 1 min of continuing selective inhibition of
      oxidative metabolism. The toxic potency and effectiveness of glutamate were
      enhanced during metabolic inhibition, showing that receptors were not inactivated
      by simulated ischemia. These results are consistent with the specific hypothesis
      that return of oxidative metabolism triggers a critical period of toxic NMDA
      receptor activation.

PMID- 7561866
TI  - Comparison of in vitro ischemia-induced disturbances in energy metabolism and
      protein synthesis in the hippocampus of rats and gerbils.
AB  - To elucidate whether the high sensitivity of gerbil compared with rat hippocampus
      to metabolic stress results from tissue-specific or hemodynamic factors, ischemia
      induced metabolic disturbances [energy metabolism and protein synthesis rate
      (PSR)] were studied using the in vitro model of the hippocampal slice
      preparation. At the end of in vitro ischemia, ATP content was measured in
      individual slices with HPLC. In other groups of slices, PSR was measured after
      120 min of recovery after in vitro ischemia. ATP breakdown was almost identical
      in rat and gerbil slices at all temperatures (37 degrees C, 34 degrees C, or 31
      degrees C) and periods of ischemia (5, 10, or 15 min) studied. In contrast to the
      identical rate of ATP depletion during ischemia, however, postischemic
      disturbances in PSR were significantly increased in gerbil slices compared with
      rat slices and this relationship was stable after different periods of ischemia
      and at different incubation temperatures. The results illustrate that the pattern
      of ischemia-induced disturbances observed in vivo can also be reproduced using
      the in vitro model of hippocampal slice preparation, as evidenced by the
      postischemic disturbance in PSR. It is concluded that comparison of the extent of
      metabolic disturbances in gerbil and rat hippocampal slices after transient in
      vitro ischemia may help to elucidate the mechanisms of ischemic cell damage.

PMID- 7561867
TI  - Effect of reperfusion following cerebral ischaemia on the activity of the
      mitochondrial respiratory chain in the gerbil brain.
AB  - The effect of reperfusion following 30 min of cerebral ischaemia on brain
      mitochondrial respiratory chain activity has been studied in the gerbil. The
      state 3 respiration rates with both FAD- and NAD-linked substrates were reduced
      after ischaemia. After 5 min of reperfusion, state 3 respiration with FAD-linked
      substrates was restored, but levels of NAD-linked substrates did not return to
      control values until 30 min of reperfusion. By 120 min of reperfusion state 3
      respiration decreased relative to control values with all substrates studied.
      Measurement of the individual respiratory chain complexes showed that complex I,
      complex II-III, and complex V activities were reduced after ischaemia. By 5 min
      of reperfusion complex II-III activity was restored, but the activities of
      complexes I and V did not return to control values until 30 min of reperfusion.
      In contrast, complex IV activity was unaffected by ischaemia or 5 and 30 min of
      reperfusion but was significantly reduced after 120 min of reperfusion, possibly
      owing to free radical production and lipid peroxidation.

PMID- 7561868
TI  - Glutamate release and free radical production following brain injury: effects of
      posttraumatic hypothermia.
AB  - Posttraumatic hypothermia reduces the extent of neuronal damage in remote
      cortical and subcortical structures following traumatic brain injury (TBI). We
      evaluated whether excessive extracellular release of glutamate and generation of
      hydroxyl radicals are associated with remote traumatic injury, and whether
      posttraumatic hypothermia modulates these processes. Lateral fluid percussion was
      used to induce TBI in rats. The salicylate-trapping method was used in
      conjunction with microdialysis and HPLC to detect hydroxyl radicals by
      measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA).
      Extracellular glutamate was measured from the same samples. Following trauma,
      brain temperature was maintained for 3 h at either 37 or 30 degrees C. Sham
      trauma animals were treated in an identical manner. In the normothermic group,
      TBI induced significant elevations in 2,3-DHBA (3.3-fold, p < 0.01), 2,5-DHBA
      (2.5-fold, p < 0.01), and glutamate (2.8-fold, p < 0.01) compared with controls.
      The levels of 2,3-DHBA and glutamate remained high for approximately 1 h after
      trauma, whereas levels of 2,5-DHBA remained high for the entire sampling period
      (4 h). Linear regression analysis revealed a significant positive correlation
      between integrated 2,3-DHBA and glutamate concentrations (p < 0.05).
      Posttraumatic hypothermia resulted in suppression of both 2,3- and 2,5-DHBA
      elevations and glutamate release. The present data indicate that TBI is followed
      by prompt increases in both glutamate release and hydroxyl radical production
      from cortical regions adjacent to the impact site. The magnitude of glutamate
      release is correlated with the extent of the hydroxyl radical adduct, raising the
      possibility that the two responses are associated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7561869
TI  - Phosphorylation of VAMP/synaptobrevin in synaptic vesicles by endogenous protein
      kinases.
AB  - VAMP/synaptobrevin (SYB), an integral membrane protein of small synaptic
      vesicles, is specifically cleaved by tetanus neurotoxin and botulinum neurotoxins
      B, D, F, and G is thought to play an important role in the docking and/or fusion
      of synaptic vesicles with the presynaptic membrane. Potential phosphorylation
      sites for various kinases are present in SYB sequence. We have studied whether
      SYB is a substrate for protein kinases that are present in nerve terminals and
      known to modulate neurotransmitter release. SYB can be phosphorylated within the
      same vesicle by endogenous Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      associated with synaptic vesicles. This phosphorylation reaction occurs rapidly
      and involves serine and threonine residues in the cytoplasmic region of SYB.
      Similarly to CaMKII, a casein kinase II (CasKII) activity copurifying with
      synaptic vesicles is able to phosphorylate SYB selectively on serine residues of
      the cytoplasmic region. This phosphorylation reaction is markedly stimulated by
      sphingosine, a sphingolipid known to activate CasKII and to inhibit CaMKII and
      protein kinase C. The results show that SYB is a potential substrate for protein
      kinases involved in the regulation of neurotransmitter release and open the
      possibility that phosphorylation of SYB plays a role in modulating the molecular
      interactions between synaptic vesicles and the presynaptic membrane.

PMID- 7561870
TI  - Metabolic and energetic changes during apoptosis in neural cells.
AB  - Changes in cellular energetic and metabolic parameters were analyzed at several
      time points during apoptosis of differentiated PC12 cells following removal of
      nerve growth factor (NGF). As approximately 60% of the population died during the
      period of study (24 h), most of the measured metabolic indicators declined over
      time. However, this decline paralleled the overall decrease in cellular
      viability, suggesting that, in individual cells, a compromised metabolic state
      occurred suddenly and very late in the death process. For example, when expressed
      as a function of viable cells, protein and RNA synthesis did not decrease until
      24 h. Glucose utilization in live cells was never significantly reduced relative
      to control levels; lactate production decreased slightly within 4-8 h after NGF
      removal, but eventually rebounded to 122% of control levels by 24 h. ATP levels
      dropped 27% in an early predeath period, but then returned to near control levels
      (on a per-live-cell basis) once the population actively began to die. The ATP/ADP
      ratio remained at least 84% of control throughout. UTP/UDP and GTP/GDP ratios did
      not change significantly at any time point.

PMID- 7561871
TI  - Convulsant agents activate c-fos induction in both a calmodulin-dependent and
      calmodulin-independent manner.
AB  - Calcium acts as a second messenger and can enter neurons through several types of
      calcium channel. We sought to determine whether the calcium-dependent mechanisms
      inducing c-fos expression are identical following activation, by appropriate
      drugs, of L-type voltage-sensitive calcium channels or NMDA and non-NMDA
      receptors or following inhibition of the GABAergic system. We used primary
      cortical neurons and OF1 mice, and the levels of c-fos protein and c-fos mRNA
      were detected after treatment with the drugs by means of immunocytochemistry and
      in situ hybridization. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W-7) abolished gamma-hexachlorocyclohexane-, Bay K 8644-,
      pentylenetetrazole-, and kainic acid-induced increases in c-fos expression in
      cultured neurons. Conversely, W-7 did not affect either NMDA- or picrotoxinin
      mediated increases in c-fos expression. In mice, the pattern of protooncogene
      expression displayed some differences compared with cultured neurons, depending
      on the treatment. W-7 administered before gamma-hexachlorocyclohexane, Bay K
      8644, or pentylenetetrazole blocked the expression of c-fos elicited by these
      compounds. However, W-7 was not able to abolish c-fos expression induced by
      picrotoxinin. In the animals treated with W-7 before kainic acid or NMDA
      administration, c-fos expression was inhibited in cerebral cortex, but it was
      still present in hippocampus. These results agree with the existence of diverse
      mechanisms transducing the calcium signals to the nucleus. Calmodulin may mediate
      neuronal responses depending on the route by which calcium enters the neuron,
      resulting in activation of different enzymes.

PMID- 7561872
TI  - Neurotrophic factors attenuate glutamate-induced accumulation of peroxides,
      elevation of intracellular Ca2+ concentration, and neurotoxicity and increase
      antioxidant enzyme activities in hippocampal neurons.
AB  - Exposure of cultured rat hippocampal neurons to glutamate resulted in
      accumulation of cellular peroxides (measured using the dye 2,7
      dichlorofluorescein). Peroxide accumulation was prevented by an N-methyl-D
      aspartate (NMDA) receptor antagonist and by removal of extracellular Ca2+,
      indicating the involvement of NMDA receptor-induced Ca2+ influx in peroxide
      accumulation. Glutamate-induced reactive oxygen species contributed to loss of
      Ca2+ homeostasis and excitotoxic injury because antioxidants (vitamin E, propyl
      gallate, and N-tert-butyl-alpha-phenylnitrone) suppressed glutamate-induced
      elevation of intracellular Ca2+ concentration ([Ca2+]i) and cell death. Basic
      fibroblast growth factor (bFGF), nerve growth factor (NGF), and brain-derived
      neurotrophic factor (BDNF), but not ciliary neurotrophic factor, each suppressed
      accumulation of peroxides induced by glutamate and protected neurons against
      excitotoxicity. bFGF, NGF, and BDNF each increased (to varying degrees) activity
      levels of superoxide dismutases and glutathione reductase. NGF increased catalase
      activity, and BDNF increased glutathione peroxidase activity. The ability of the
      neurotrophic factors to suppress glutamate toxicity and glutamate-induced
      peroxide accumulation was attenuated by the tyrosine kinase inhibitor genistein,
      indicating the requirement for tyrosine phosphorylation in the neuro-protective
      signal transduction mechanism. The data suggest that glutamate toxicity involves
      peroxide production, which contributes to loss of Ca2+ homeostasis, and that
      induction of antioxidant defense systems is a mechanism underlying the [Ca2+]i
      stabilizing and excitoprotective actions of neurotrophic factors.

PMID- 7561873
TI  - Fatty acids from degenerating myelin lipids are conserved and reutilized for
      myelin synthesis during regeneration in peripheral nerve.
AB  - Following nerve crush, cholesterol from degenerating myelin is conserved and
      reutilized for new myelin synthesis during nerve regeneration. The possibility
      that other myelin lipids are salvaged and reutilized has not been investigated
      previously. We examined the fate of myelin phospholipids and their fatty acyl
      moieties following nerve crush by electron microscopic autoradiography of myelin
      lipids prelabeled with [3H]oleate or [2-3H]-glycerol. Both precursors were
      incorporated predominantly (> 90%) into phospholipids; > 85% of the [3H]-oleate
      was incorporated as oleate, with the remainder in longer-chain fatty acids.
      Before nerve crush, both labels were restricted to myelin sheaths. Following
      nerve crush and subsequent regeneration, over half the label from [3H]oleate, but
      little from [2-3H]glycerol, remained in nerve. The oleate label was present as
      fatty acyl moieties in phospholipids and was localized to newly formed myelin
      sheaths. Among the extracellular soluble lipids within the degenerating nerve,
      the bulk of the labeled phospholipids floated at the same density as lipoprotein
      particles. These data indicate that myelin phospholipids are completely
      hydrolyzed during nerve degeneration, that at least half the resultant free fatty
      acids are salvaged and reutilized for new myelin synthesis, and that these
      salvaged fatty acids are transported by a lipoprotein-mediated mechanism similar
      to that functioning in cholesterol reutilization.

PMID- 7561874
TI  - Transglutaminase cross-linking of the tau protein.
AB  - Tissue transglutaminase (EC 2.3.2.13) is a calcium-activated enzyme that cross
      links specific substrate proteins into insoluble, protease-resistant, high
      molecular weight complexes. Because the neurofibrillary tangles in Alzheimer
      disease have similar biochemical characteristics, and because the microtubule
      associated protein tau is the predominant component of these structures, the
      substrate properties of tau with respect to transglutaminase were investigated.
      Bovine tau and recombinant human tau isoforms rapidly form high molecular weight,
      cross-linked polymers on incubation with transglutaminase. Polyamine
      incorporation assays indicate that bovine tau is an excellent substrate of
      transglutaminase, with a Km of 10.4 +/- 2.2 microM and a Vmax of 40.9 +/- 4.5
      nmol/mg of enzyme/min. Individual recombinant human tau isoforms are not
      equivalent with respect to transglutaminase, as the smallest isoform T3 (352
      amino acids) is not as good a substrate as the larger isoforms T4 (383 amino
      acids) and T4L (441 amino acids). To determine which segments of the tau protein
      are susceptible to modification by transglutaminase, tau was labeled with
      [3H]putrescine by transglutaminase and proteolyzed with alpha-chymotrypsin, and
      the breakdown products were analyzed. These experiments demonstrate that the
      enzyme modifies tau at only one or a few discrete sites, primarily in the
      carboxyl half of the molecule. Thus, the reaction is specific for only a small
      number of the many glutamine residues in tau. Furthermore, a tau deletion
      construct (T264) containing a portion of the microtubule-binding domains, which
      is a substrate of transglutaminase, cannot be cross-linked by the enzyme. This
      provides evidence that the cross-linking reaction is specific, and requires that
      the substrates be appropriately associated for cross-linking to occur.

PMID- 7561875
TI  - Characteristics of the chromaffin granule aspartic proteinase involved in
      proenkephalin processing.
AB  - Proteolytic processing of neuropeptide precursors is required for production of
      active neurotransmitters and hormones. In this study, a chromaffin granule (CG)
      aspartic proteinase of 70 kDa was found to contribute to enkephalin precursor
      cleaving activity, as assayed with recombinant ([35S]Met) preproenkephalin. The
      70-kDa CG aspartic proteinase was purified by concanavalin A-Sepharose, Sephacryl
      S-200, and pepstatin A agarose affinity chromatography. The proteinase showed
      optimal activity at pH 5.5. It was potently inhibited by pepstatin A, a selective
      aspartic proteinase inhibitor, but not by inhibitors of serine, cysteine, or
      metalloproteinases. Lack of inhibition by Val-D-Leu-Pro-Phe-Val-D-Leu--an
      inhibitor of pepsin, cathepsin D, and cathepsin E--distinguishes the CG aspartic
      proteinases from classical members of the aspartic proteinase family. The CG
      aspartic proteinase cleaved recombinant proenkephalin between the Lys172-Arg173
      pair located at the COOH-terminus of (Met)enkephalin-Arg6-Gly7-Leu8, as assessed
      by peptide microsequencing. The importance of full-length prohormone as substrate
      was demonstrated by the enzyme's ability to hydrolyze 35S-labeled proenkephalin
      and proopiomelanocortin and its inability to cleave tri- and tetrapeptide
      substrates containing dibasic or monobasic cleavage sites. In this study, results
      provide evidence for the role of an aspartic proteinase in proenkephalin and
      prohormone processing.

PMID- 7561876
TI  - Induction of a nerve growth factor-sensitive kinase that phosphorylates the DNA
      binding domain of the orphan nuclear receptor NGFI-B.
AB  - Nerve growth factor (NGF) induces the synthesis and the phosphorylation of the
      orphan nuclear receptor NGFI-B in PC12 cells. Previous work has shown that
      phosphorylation, by protein kinase A, of a specific serine in the DNA-binding
      domain inhibits its binding to the NGFI-B response element. Also, cytoplasmic
      extracts from PC12 cells phosphorylate this serine, and phosphorylation is
      greater in extracts from cells treated with NGF. The present work describes the
      induction, identification, and partial purification of a kinase (termed NGFI-B
      kinase I) from PC12 cell extracts that catalyzes this phosphorylation.
      Phosphorylation of the DNA-binding domain with this purified preparation inhibits
      its binding to the NGFI-B response element. The kinase is rapidly activated by
      treatment of the cells with NGF, and the activation lasts for at least several
      hours. It also is activated by fibroblast growth factor and epidermal growth
      factor (EGF), but the activation by EGF is quite transient. The kinase requires
      Mg2+ but will use Mn2+. The molecular mass of the kinase is 95-100 kDa, and it is
      different from protein kinase A, Fos kinase, or pp90rsk. Comparison with a
      partially purified preparation of cyclic AMP response element-binding protein
      kinase, however, indicates that the two are either very similar or identical.

PMID- 7561877
TI  - Differential targeting to the plasma membrane of the Torpedo 15-kDa proteolipid
      expressed in oocytes.
AB  - Xenopus laevis oocytes were injected with poly(A)+ RNAs extracted from the
      electric lobes of Torpedo marmorata, which contain a homogeneous population of
      cholinergic neurons. These primed oocytes were able to synthesize acetylcholine
      and to release the neurotransmitter in a calcium-dependent manner. Fractionation
      of oocyte membranes as well as immunofluorescence experiments showed that the 15
      kDa proteolipid, a common subunit of the vacuolar H(+)-ATPase and of a
      presynaptic membrane protein capable of calcium-dependent acetylcholine
      translocation called the mediatophore, was located at the oocyte plasma membrane.
      In contrast, oocytes injected with separate transcripts encoding the 15-kDa
      proteolipid and choline acetyltransferase were unable to release acetylcholine in
      spite of an equivalent acetylcholine content and a higher level of 15-kDa
      proteolipid expression. We observed by immunofluorescence that under these
      conditions, the 15-kDa proteolipid was expressed in granular cytoplasmic
      membranes, which were then identified as being Golgi vesicles by cell
      fractionation. The striking difference in the distribution of the 15-kDa
      proteolipid expressed in oocytes primed with Torpedo electric lobe mRNA as
      compared with that seen in oocytes injected with the cRNA alone suggests that
      another protein endogenous to the electric lobe may be implicated in the
      localization of the 15-kDa proteolipid at the plasma membrane. Moreover, such a
      targeting mechanism could contribute to the capacity of electric lobe mRNA
      injected oocytes to release acetylcholine.

PMID- 7561878
TI  - Increase in chloride-dependent L-glutamate transport activity in synaptic
      membrane after in vitro ischemic treatment.
AB  - The effect of energy failure on Cl(-)-dependent L-glutamate (L-Glu) transport was
      examined with an in vitro preparation. Rat brain slices were incubated in low
      oxygen and glucose-deprived medium (in vitro ischemia), and a synaptic membrane
      fraction was prepared from the slices. Cl(-)-dependent L-[3H]Glu uptake into
      vesicles increased about twofold after 20 min of in vitro ischemia. The increased
      L-[3H]Glu uptake was inhibited by L-Glu, DL-2-amino-4-phosphonobutyrate, L
      homocysteic acid, L-cystine, 4,4'-diisothiocyano-2,2'-disulfonic stilbene, and
      removal of Cl-. Uptakes of Na(+)-dependent L-[3H]Glu, [3H]GABA, and [3H]taurine
      were not changed by the in vitro ischemia. In vitro ischemia increased the Vmax
      value without affecting the Km value. The increased L-[3H]Glu uptake by in vitro
      ischemia was reduced by subsequent incubation in a normoxic glucose-containing
      solution. ATP content in brain slices decreased to < 10% of control values by in
      vitro ischemia for 10 min. The decrease in ATP content was restored by subsequent
      incubation in normoxic glucose-containing solution. Treatment with veratrine, 2,4
      dinitrophenol, carbonyl cyanide m-chlorophenylhydrazone, and NaCN in normoxic
      conditions increased L-[3H]Glu uptake with a concomitant decrease in ATP content
      in slices. These results suggest that Cl(-)-dependent L-Glu transport activity in
      synaptic membranes increases in ischemia- or hypoxia-induced brain energy
      failures.

PMID- 7561879
TI  - Myelin P0 glycoprotein and a synthetic peptide containing the palmitoylation site
      are both autoacylated.
AB  - P0, the major protein of the PNS myelin, is palmitoylated at the cytoplasmic
      Cys153. To gain insights into the mechanism of P0 acylation, the in vitro
      palmitoylation of both P0 and a synthetic Cys153-containing octapeptide was
      studied. Incubation of PNS myelin membranes or isolated P0 with [3H]palmitoyl-CoA
      resulted in specific labeling of this protein, suggesting that the reaction is
      nonenzymatic. Incorporation of the labeled fatty acid into P0 was not affected by
      boiling the isolated P0 for 15 min before incubation or by adding sciatic nerve
      homogenate to the reaction mixture, which confirms the nonenzymatic nature of the
      reaction. After chemical deacylation, P0 was palmitoylated at a higher rate,
      suggesting that the original site was reacylated. Furthermore, tryptic digestion
      and peptide mapping showed that the same sites are acylated in vitro as in nerve
      slices indicating that the reaction has physiological significance. On incubation
      with [14C]palmitoyl-CoA, the synthetic peptide encompassing the natural P0
      acylation site (I150RYCWLRR157) was also spontaneously acylated at the cysteine
      residue. Thus, the integrity of the protein is not required for the nonenzymatic
      transacylation reaction. At pH 7.4 and 37 degrees C, peptide palmitoylation
      followed a second-order reaction (k2 = 246 +/- 6 M-1 min-1) and is likely a
      bimolecular nucleophilic substitution with the peptide thiolate attacking the
      highly reactive thioester bond in palmitoyl-CoA. The activation energy calculated
      from the Arrhenius plot is approximately 2 kcal/mol and much lower than that of
      enzyme-catalyzed transacylations. Finally, two other P0 peptides (V121PTRYG126
      and K109TSQVTL115) as well as various unrelated thiol-containing compounds,
      including cysteine, glutathione, pressinoic acid (CYFQNC), and crustacean
      cardioactive peptide (PFCNAFTGC), were not autoacylated. These results indicate
      that the IRYCWLRR peptide represents a particular structural motif and/or has
      some chemical features that allow the reaction to occur spontaneously.

PMID- 7561880
TI  - Transient increase of cyclic AMP induced by glutamate in cultured neurons from
      rat spinal cord.
AB  - We demonstrated that glutamate increased the cyclic AMP level in cultured neurons
      from rat spinal cord. A bath application of glutamate (300 microM) elicited a
      rapid increase of the cyclic AMP concentration reaching a level three times as
      high as the basal level in approximately 3 min, and its content then decreased to
      the control level in 15 min. The increase was not observed in a Ca(2+)-free
      medium and was inhibited by an antagonist of NMDA receptors or a voltage
      sensitive Ca2+ channel blocker. Preincubation with W7 also inhibited the
      glutamate-evoked cyclic AMP increase. NMDA, aspartate, and high-K+ conditions
      also induced a cyclic AMP increase; however, a decreasing phase did not follow.
      The decreasing phase was observed when (2S,1'S,2'S)-2-(carboxycyclopropyl)
      glycine, a potent agonist for metabotropic glutamate receptors, was combined with
      NMDA. These results suggest that the cyclic AMP increase is mediated by a Ca2+
      influx via both NMDA receptors and voltage-sensitive Ca2+ channels followed by an
      activation of the Ca2+/calmodulin system, and the decreasing phase observed in
      the case of glutamate exposure is due to the activation of the metabotropic
      glutamate receptors.

PMID- 7561881
TI  - hVH-5: a protein tyrosine phosphatase abundant in brain that inactivates mitogen
      activated protein kinase.
AB  - A novel protein tyrosine phosphatase [homologue of vaccinia virus H1 phosphatase
      gene clone 5 (hVH-5)] was cloned; it shared sequence similarity with a subset of
      protein tyrosine phosphatases that regulate mitogen-activated protein kinase. The
      catalytic region of hVH-5 was expressed as a fusion protein and was shown to
      hydrolyze p-nitrophenylphosphate and inactivate mitogen-activated protein kinase,
      thus proving that hVH-5 possessed phosphatase activity. A unique proline-rich
      region distinguished hVH-5 from other closely related protein tyrosine
      phosphatases. Another feature that distinguished hVH-5 from related phosphatases
      was that hVH-5 was expressed predominantly in the adult brain, heart, and
      skeletal muscle. In addition, in situ hybridization histochemistry of mouse
      embryo revealed high levels of expression and a wide distribution in the central
      and peripheral nervous system. Some specific areas of abundant hVH-5 expression
      included the olfactory bulb, retina, layers of the cerebral cortex, and cranial
      and spinal ganglia. hVH-5 was induced in PC12 cells upon nerve growth factor and
      insulin treatment in a manner characteristic of an immediate-early gene,
      suggesting a possible role in the signal transduction cascade.

PMID- 7561882
TI  - Tyrosine phosphorylation in a model of ischemia using the rat hippocampal slice:
      specific, long-term decrease in the tyrosine phosphorylation of the postsynaptic
      glycoprotein PSD-GP180.
AB  - The effects of the exposure of hippocampal slices to brief periods of ischemic
      like conditions on the tyrosine phosphorylation of proteins and glycoproteins
      were investigated. Freshly prepared hippocampal slices contained a range of
      tyrosine-phosphorylated proteins and two prominent tyrosine-phosphorylated
      glycoproteins of apparent M(r) 110,000 (GP110) and 180,000, which we have
      previously shown to correspond to the postsynaptic density (PSD)-associated
      glycoprotein PSD-GP180. When hippocampal slices were incubated in oxygenated
      Krebs-Ringer buffer containing 10 mM glucose (KRB), there was a transient
      increase in the tyrosine phosphorylation of a protein of M(r) 42,000 (p42) and a
      pronounced increase in the tyrosine phosphorylation of GP110. After these initial
      changes, the tyrosine phosphorylation of all proteins remained constant for at
      least 60 min. In vitro "ischemia" was achieved by transferring slices that had
      been preincubated for 60 min in KRB to KRB that had been equilibrated with N2
      instead of O2 and that did not contain glucose. Tyrosine-phosphorylated GP110 and
      PSD-GP180 could no longer be detected after 10 min of exposure of the slices to
      ischemic-like conditions. GP110 was rapidly rephosphorylated on tyrosine after
      transfer of slices back to oxygenated, glucose-containing buffer. In contrast,
      short periods of ischemia (5 or 10 min) resulted in the long-term loss of
      phosphotyrosine [Tyr(P)]-PSD-GP180 so that it was not detected even after 60 min
      of reincubation in oxygenated KRB. The sustained decrease in tyrosine
      phosphorylation of PSD-GP180 after ischemia was Ca2+ dependent, the levels of
      Tyr(P)-PSD-GP180 slowly increasing to preischemic values if Ca2+ was omitted from
      the incubation media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561883
TI  - Action of beta-N-oxalylamino-L-alanine on mouse brain NADH-dehydrogenase
      activity.
AB  - beta-N-Oxalylamino-L-alanine (L-BOAA), a non-protein neuroexcitatory amino acid
      present in the seeds of Lathyrus sativus (chickling or grass pea), is known to
      produce its neurotoxic effects by overstimulation of non-N-methyl-D-aspartate
      receptors, especially alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA) receptors, at micromolar concentrations. It has recently been reported
      that L-BOAA selectively inhibits mitochondrial enzyme NADH-dehydrogenase (NADH
      DH) in brain slices at subpicomolar concentrations. The present study finds that
      up to 4 mM concentrations of pure L-BOAA fail to inhibit NADH-DH activity in
      mouse brain homogenate and isolated brain mitochondria. Two known inhibitors
      (rotenone and 1-methyl-4-phenylpyridinium ion, MPP+) of this mitochondrial enzyme
      produced significant inhibition under identical conditions. NADH-DH inhibition
      was also not observed in the homogenate or mitochondria from the brains of
      animals systemically treated with convulsive doses of L-BOAA. Some inhibition (20
      37%) of NADH-DH activity was observed in mouse brain slices incubated with 100
      1,000 microM concentrations of L-BOAA for 1 h at 37 degrees C in an atmosphere of
      95% O2 and 5% CO2, but the inhibition was nonselective, because the activity of
      another mitchondrial enzyme, succinic dehydrogenase, was similarly inhibited by L
      BOAA. These results are in contrast with the report that L-BOAA inhibits
      mitochondrial NADH-DH selectively at subpicomolar concentrations. We suggest the
      observed nonselective NADH-DH inhibition in mouse brain slices treated with L
      BOAA is caused by neuronal damage through an excitotoxic mechanism.

PMID- 7561884
TI  - ATP-binding proteins on the external surface of synaptic plasma membranes:
      identification by photoaffinity labeling.
AB  - 8-Azidoadenosine triphosphate labeled in the alpha or gamma position with 32P was
      used as a photoaffinity reagent for identifying ATP binding sites on the external
      surface of intact rat brain synaptosomes. As revealed by autoradiography of
      sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns. UV
      irradiation of intact synaptosomes in the presence of the above radioactive
      compounds at 5-10 microM resulted in the formation of several major radioactive
      conjugates with approximate molecular masses of 29, 45/46, 58, and 93 kDa. Minor
      bands of 20, 39, 52/54, 82/84, 120, and 140 kDa were also consistently labeled in
      these experiments. The possibility that labeling of these proteins was due to the
      presence of contaminating subcellular particles or intrasynaptosomal proteins was
      excluded. The major 8-azidoadenosine [alpha-32P]triphosphate-labeled protein
      complex of approximately 45/46 kDa was resolved into several subbands that are
      labeled differently depending on the type of divalent cations added to the
      photoaffinity reaction. In the presence of magnesium only, the major labeled band
      appeared at 45 kDa. With calcium, two additional subbands (43 and 46 kDa) could
      be distinguished. In the presence of 1 mM EDTA, a band at 44 kDa was labeled
      within this ATP-binding complex. The labeling pattern of the subbands of this
      45/46-kDa complex is consistent with these bands being extracellular ATP-binding
      proteins on the surface of the synaptosome.

PMID- 7561885
TI  - Effects of brefeldin A on synthesis and intracellular transport of ganglioside
      GT3 by chick embryo retina cells.
AB  - Ganglioside GT3 is the precursor of c-series gangliosides. It is synthesized by
      sialylation of GD3 and is expressed in nervous tissue of birds and mammals at
      early stages of development. In this study we examined the sub-Golgi location of
      GT3 synthesis and the mechanism of its transport from the site of synthesis to
      the plasma membrane in chicken embryo retina cells in culture. Neural retina
      cells from 10-day-old chick embryo were cultured with [3H]galactose in the
      absence (control cells) or in the presence of 1 micrograms/ml brefeldin A (BFA).
      At the end of the labeling period, the fraction of labeled gangliosides
      transported to the plasma membrane was determined. For this, cells were treated
      with C. perfringens neuraminidase in conditions to desialylate only those
      gangliosides that were transported to the plasma membrane and consequently
      accessible to the enzyme. After neuraminidase treatment of cells, gangliosides
      were isolated, purified, and the pattern of radioactivity analyzed by HPTLC
      fluorography. It was found that BFA blocked the synthesis of complex gangliosides
      without affecting the synthesis of GM3, GD3, and GT3. Furthermore, in BFA-treated
      cells, GM3, GD3, and GT3 were protected from the action of added neuraminidase,
      indicating an intracellular localization and, hence, an inhibition of their
      transport to the plasma membrane. The results indicate that synthesis of the
      first intermediates of a-, b-, and c- series gangliosides occurs in a proximal
      Golgi compartment and that the proximal Golgi-synthesized gangliosides (GM3, GD3,
      and GT3) use a transport mechanism that is dependent on ADP ribosylation factor
      and coatomer proteins.

PMID- 7561886
TI  - Effects of brefeldin A on galactosphingolipid synthesis in an immortalized
      Schwann cell line: evidence for different intracellular locations of
      galactosylceramide sulfotransferase and ceramide galactosyltransferase
      activities.
AB  - Brefeldin A (BFA) has been used extensively to study the intracellular transport
      and processing of proteins and sphingolipids because of its dramatic alteration
      of the structural and functional organization of the Golgi. We have examined the
      effect of BFA on the synthesis of galactosylceramide sulfate (SGalCer) and its
      immediate precursor galactosylceramide (GalCer) in an immortalized Schwann cell
      line (S16) to determine the intracellular sites of synthesis of these two related
      glycolipids. During a 6-h labeling period, a dose-dependent inhibition of
      [35S]sulfate incorporation into SGalCer was observed with 95% inhibition
      occurring at 0.5 microgram/ml BFA. Labeling of newly synthesized
      galactosphingolipids with [3H]-palmitic acid for 6 h in the presence of BFA
      resulted in increased incorporation of label into GalCer containing nonhydroxy
      fatty acids (NFA-GalCer) to 162% of control values, whereas labeling of GalCer
      containing 2-hydroxy fatty acids (HFA-GalCer) was reduced to 63% of control.
      After 24 h, these values were at 366 and 91%, respectively. These results
      indicate that at least some of the HFA-GalCer was initially synthesized at a
      location distal to the BFA block and separate from the site of NFA-GalCer
      synthesis. Examination of [3H]palmitic acid incorporation into free ceramides
      showed an increase of 133 and 161% for hydroxy and nonhydroxy fatty acid
      ceramides, respectively, in cells treated for 6 h with BFA in comparison with
      levels found in untreated control cells, indicating that BFA did not block fatty
      acid 2-hydroxylation or the formation of HFA ceramide.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7561888
TI  - Zolpidem displays heterogeneity in its binding to the nonhuman primate
      benzodiazepine receptor in vivo.
AB  - The distinctive pharmacological activity of zolpidem in rats compared with
      classical benzodiazepines has been related to its differential affinity for
      benzodiazepine receptor (BZR) subtypes. By contrast, in nonhuman primates the
      pharmacological activity of zolpidem was found to be quite similar to that of
      classical BZR agonists. In an attempt to explain this discrepancy, we examined
      the ability of zolpidem to differentiate BZR subtypes in vivo in primate brain
      using positron emission tomography. The BZRs were specifically labeled with
      [11C]flumazenil. Radiotracer displacement by zolpidem was monophasic in
      cerebellum and neocortex, with in vivo Hill coefficients close to 1. Conversely,
      displacement of [11C]flumazenil was biphasic in hippocampus, amygdala, septum,
      insula, striatum, and pons, with Hill coefficients significantly smaller than 1,
      suggesting two different binding sites for zolpidem. In these cerebral regions,
      the half-maximal inhibitory doses for the high-affinity binding site were similar
      to those found in cerebellum and neocortex and approximately 100-fold higher for
      the low-affinity binding site. The low-affinity binding site accounted for < 32%
      of the specific [11C]-flumazenil binding. Such zolpidem binding characteristics
      contrast with those reported for rodents, where three different binding sites
      were found. Species differences in binding characteristics may explain why
      zolpidem has a distinctive pharmacological activity in rodents, whereas its
      pharmacological activity in primates is quite similar to that of classical BZR
      agonists, except for the absence of severe effects on memory functions, which may
      be due to the lack of substantial zolpidem affinity for a distinct BZR subtype in
      cerebral structures belonging to the limbic system.

PMID- 7561887
TI  - Presynaptic nicotinic receptors stimulate increases in intraterminal calcium of
      chick sympathetic neurons in culture.
AB  - Stimulation of chick sympathetic neurons in culture by the cholinergic agonists
      acetylcholine, nicotine, and 1,1-dimethyl-4-phenylpiperazinium (all at 10-1,000
      mumol/L) induced concentration-dependent increases of free calcium levels
      measured by fura 2 fluorescence in neuronal processes. The response evoked by
      acetylcholine had both nicotinic and muscarinic components, whereas that induced
      by 1,1-dimethyl-4-phenylpiperazinium was purely nicotinic. Tetrodotoxin (0.3
      mumol/L) blocked completely the increase of intraterminal free calcium level
      evoked by electrical stimulation. On the other hand, stimulation with 1,1
      dimethyl-4-phenylpiperazinium still evoked 20-25% of the control response in the
      presence of tetrodotoxin. The concentration-response relationship of 1,1-dimethyl
      4-phenylpiperazinium stimulation did not differ in the absence and in the
      presence of tetrodotoxin. The nicotinic antagonists d-tubocurarine (10 mumol/L)
      and mecamylamine (10 mumol/L), but not alpha-bungarotoxin (125 nmol/L), prevented
      the increase of intraterminal free calcium level evoked by 1,1-dimethyl-4
      phenylpiperazinium (100 mumol/L) in the presence of tetrodotoxin. These
      observations indicate the presence of nicotinic receptors on neuronal processes
      that increase the intraterminal concentration of free calcium and probably
      modulate transmitter release. Their pharmacological properties are similar to
      those of nicotinic receptors located on neuronal cell bodies.

PMID- 7561889
TI  - Nyctohemeral rhythm in the levels of S-adenosylmethionine in the rat pineal gland
      and its relationship to melatonin biosynthesis.
AB  - Liquid chromatographic techniques that permit the simultaneous analysis of S
      adenosylmethionine, melatonin, and its intermediary metabolites N-acetyl-5
      hydroxytryptamine and 5-hydroxytryptamine within individual pineal glands have
      been developed. S-Adenosylmethionine has been shown to undergo a marked
      nyctohemeral rhythm in the pineal gland of the rat, with maximal levels occurring
      during the light period and minimal levels during the dark period. Detailed
      studies of the temporal relationships between the levels of S-adenosylmethionine
      and those of melatonin and its intermediary metabolites suggest that an
      association exists between the levels of S-adenosylmethionine and the status of
      the biosynthesis of melatonin. Exposure of animals to continuous light and the
      administration of the beta-adrenoreceptor antagonist propranolol were both found
      to inhibit the induction of melatonin synthesis and prevent the reduction in the
      levels of S-adenosylmethionine during the dark period. As a corollary the
      induction of melatonin biosynthesis following the administration of the beta
      adrenoreceptor agonist isoproterenol during the light period was accompanied by a
      marked decrease in the levels of S-adenosylmethionine in the pineal gland. The
      significance of the link between the nyctohemeral rhythms in the levels of S
      adenosylmethionine and the biosynthesis of melatonin in the pineal gland is
      discussed in the context of the therapeutic efficacy of S-adenosylmethionine as
      an antidepressant.

PMID- 7561890
TI  - Schwannoma-derived growth factor interacts with the epidermal growth factor
      receptor.
AB  - Schwannoma-derived growth factor (SDGF) is a potent mitogen and neuronal
      differentiation factor. Because of its relationship to epidermal growth factor
      (EGF) and the heregulins, it was asked if SDGF interacts with the EGF receptor or
      HER2/neu. SDGF binds to and causes the phosphorylation on tyrosine of the EGF
      receptor but not HER2/neu.

PMID- 7561892
TI  - Docosahexaenoate turnover in brain phospholipids.

PMID- 7561891
TI  - Enhancement of beta-amyloid peptide A beta(1-40)-mediated neurotoxicity by
      glutamine synthetase.
AB  - The beta-amyloid peptide (A beta), a main constituent in both senile and diffuse
      plaques in Alzheimer's disease brains, was previously shown to be neurotoxic and
      to be able to interact with several macromolecular components of brain tissue.
      Previous investigations carried out in our laboratory demonstrated free radical
      species formation in aqueous solutions of A beta(1-40) and its C-end fragment, A
      beta(25-35). Toxic forms of A beta rapidly inactivate the oxidation-sensitive
      cytosolic enzyme glutamine synthetase (GS). In this regard, we suggested and
      subsequently demonstrated that A beta radicals can cause an oxidative damage of
      cell proteins and lipids resulting in disruption of membrane functions, enzyme
      inactivation, and cell death. Because GS can be a substrate for A beta-derived
      oxidizing species, the present study was conducted to determine if GS could
      protect against A beta neurotoxicity. In contrast to this initial hypothesis, we
      here report that GS significantly enhances the neurotoxic effects of A beta(1
      40). The A beta-mediated inactivation of GS was found to be accompanied by the
      loss of immunoreactive GS and the significant increase of A beta(1-40)
      neurotoxicity.

PMID- 7561893
TI  - Taxane-specific monoclonal antibodies: measurement of taxol, baccatin III, and
      "total taxanes" in Taxus brevifolia extracts by enzyme immunoassay.
AB  - Three monoclonal antibodies with either specificity to taxol or baccatin III, or
      cross-reactivity with several common taxanes have been prepared and used to
      develop sensitive competitive-inhibition enzyme immunoassays. The hybridomas
      producing these monoclonal antibodies were obtained by fusing P3X63Ag8.653
      plasmacytoma cells and splenocytes from mice hyperimmunized with keyhole limpet
      hemocyanin-7-succinyltaxol or -7-succinylbaccatin III conjugates. Direct and
      indirect competitive inhibition enzyme immunoassays were developed with these
      monoclonal antibodies and microtiter plates coated with bovine serum albumin
      conjugates of the complementary hapten. Detection limits for the direct
      competitive inhibition enzyme immunoassays, conducted in buffer containing 10%
      MeOH, were 0.6 nM taxol for 3C6 (anti-taxol); 1.1 nM baccatin III for 3H5 (anti
      baccatin III); and 0.6 nM taxol or baccatin III for 8A10 (anti-taxane). The
      immunoassays accurately detected taxol, baccatin III, and "total taxanes" in
      crude MeOH extracts of Taxus brevifolia bark and in hplc fractions of these
      extracts.

PMID- 7561894
TI  - Immunoenzymatic methods applied to the search for bioactive taxoids from Taxus
      baccata.
AB  - Polyclonal antibodies raised against 2'-succinyltaxol-bovine serum albumin (BSA)
      conjugate were used for the immunodetection of bioactive taxoids in
      chromatographic fractions of the stem bark extract of Taxus baccata. In addition
      to taxol, cephalomannine, and baccatin III, two taxoids were isolated and their
      structures were elucidated as 4 alpha,7 beta-diacetoxy-2 alpha,9 alpha-dibenzoxy
      5 beta,20-epoxy-10 beta, 13 alpha, 15-trihydroxy-11(15-->1)-abeo-tax-11-ene[5]
      and taxol C [6] using spectroscopic methods.

PMID- 7561895
TI  - Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1 reverse
      transcriptase.
AB  - Swertifrancheside [1], a new flavonone-xanthone glucoside isolated from Swertia
      franchetiana, 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2], a
      triterpene isolated from the roots of Maprounea africana, and protolichesterinic
      acid [3], an aliphatic alpha-methylene-gamma-lactone isolated from the lichen
      Cetraria islandica, were found to be potent inhibitors of the DNA polymerase
      activity of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT), with
      50% inhibitory doses (IC50 values) of 43, 3.7, and 24 microM, respectively. They
      were not cytotoxic with cultured mammalian cells. The kinetic mechanisms by which
      compounds 1-3 inhibited HIV-1 RT were studied as was their potential to inhibit
      other nucleic acid polymerases. Swertifrancheside [1] bound to DNA and was shown
      to be a competitive inhibitor with respect to template-primer, but a mixed-type
      competitive inhibitor with respect to TTP. On the other hand, 1 beta
      hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and protolichesterinic acid [3]
      were mixed-type competitive inhibitors with respect to template-primer and
      noncompetitive inhibitors with respect to TTP. Therefore, the mechanism of action
      of 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and protolichesterinic
      acid [3] as HIV-1 RT inhibitors involves nonspecific binding to the enzyme at
      nonsubstrate binding sites, whereas swertifrancheside [1] inhibits enzyme
      activity by binding to the template-primer.

PMID- 7561896
TI  - Bruceosides D, E, and F, three new cytotoxic quassinoid glucosides from Brucea
      javanica.
AB  - Three new quassinoid glucosides, bruceosides D [1], E [2], and F [3], were
      isolated from Brucea javanica, and their structures were elucidated by spectral
      evidence and chemical transformation to known compounds. Compounds 1-3 show
      selective cytotoxicity in the leukemia and non-small cell lung, colon, CNS,
      melanoma, and ovarian cancer cell lines with log GI50 values in the range of 
      4.14 to -5.72.

PMID- 7561897
TI  - A reinvestigation of Maprounea triterpenes.
AB  - Anti-HIV activity and the inhibition of phorbol ester receptor binding activity
      in two species of Maprounea were traced to small amounts of highly potent phorbol
      esters of the daphnane type. The triterpenes previously isolated from this genus
      were found to be devoid of biological activity when scrupulously purified. Four
      new triterpene esters were elucidated; two [3,4] were found in M. africana, while
      three [4,6,7] were found in M. membranacea. Nmr assignments have also been made
      for two previously known compounds [2,5] in this group.

PMID- 7561898
TI  - Addition of methyl thioglycolate and benzylamine to (Z)-ligustilide, a bioactive
      unsaturated lactone constituent of several herbal medicines. An improved
      synthesis of (Z)-ligustilide.
AB  - (Z)-Ligustilide [1] is a dihydrophthalide purported to be the active ingredient
      of Ligusticum plant species widely used as herbal medicines in the Orient and in
      Native American and Hispanic cultures. It readily underwent 1,6-conjugate
      addition with methyl thioglycolate in the presence of triethylamine. The methyl
      thioglycolate reaction also yielded a product from addition to the C-6-C-7 double
      bond and a diadduct from both 1,6-addition and addition to the C-6-C-7 bond.
      Reaction of 1 with benzylamine did not afford a 1,6-adduct, but yielded instead
      an N-benzyllactam, presumably formed by rearrangement from initial 1,2-addition
      to the carbonyl. An improved total synthesis of 1 was developed. (Z)-Ligustilide
      had weak antiviral properties and weak antimicrobial activity against Gram
      positive, Gram-negative, and yeast microorganisms. The broad biological activity
      of 1 and its electrophilic reactivity are consistent with the use of Ligusticum
      species in folk medicine.

PMID- 7561900
TI  - Antimicrobial metabolites from a bacterial symbiont.
AB  - Two types of antibiotics, namely, indoles and dithiolopyrrolones, have been
      isolated and identified from Xenorhabdus bovienii A2. Compounds 1 and 2 showed
      strong activity against Cryptococcus neoformans, compounds 3 and 4 showed strong
      activity against Botrytis cinerea, and compounds 1, 3, and 4 showed significant
      activity against Phytophthora infestants (2 was not tested). In addition, two
      lower homologues of xenorhabdins 5 and 6, namely, 6-(N-3'-methylbutanamido)-4,5
      dihydro-1,2-dithiolo[4,3-b]pyr rol-5- one [7] and 6-(N-butanamido)[4,5-dihydro
      1,2-dithiolo[4,3-b]pyrrol-5-one [8], have been isolated and characterized for the
      first time.

PMID- 7561899
TI  - A new monodesmosidic triterpenoid saponin from the seeds of Vigna unguiculata
      subsp. unguiculata.
AB  - A new triterpenoid saponin, 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-
      galactopyranosyl-(1-->4)-beta-D-glucuronopyranosyl]-soyaspogeno l B [1] was
      isolated along with cycloartenol, stigmasterol, 3-O-acetyloleanolic acid, and
      sitosterol 3-beta-D-glucoside from a methanolic extract of the seeds of Vigna
      unguiculata subsp. unguiculata. The structure of 1 was elucidated by
      spectroscopic and chemical means.

PMID- 7561901
TI  - [Cytotoxicity of aspidospermane indole alkaloids with a modified tryptamine
      chain].
AB  - Eight synthetic indole alkaloids with the aspidospermane structure have ben
      evaluated for cytotoxicity in the L-1210 cell culture test system. Two of them
      (compounds 9 and 5), bearing a modified tryptamine chain, were significantly
      active (IC50 values of 0.7 and 3.1 microM, respectively).

PMID- 7561902
TI  - Spiganthine, the cardioactive principle of Spigelia anthelmia.
AB  - Spiganthine [1] was isolated as the main cardioactive principle from medicinally
      used extracts of Spigelia anthelmia. Its structure was established by
      spectroscopic methods. The biological effect of spiganthine is characterized by a
      delay in contraction development of the heart muscle.

PMID- 7561903
TI  - Mycalolides D and E, new cytotoxic macrolides from a collection of the stony
      coral Tubastrea faulkneri.
AB  - Fractionation of a cytotoxic extract of the stony coral Tubastrea faulkneri
      yielded a series of cytotoxic polyoxazole macrolides and several noncytotoxic
      indole derivatives. Two new macrolides, mycalolides D [1] and E [2], were
      isolated and identified, in addition to the known compound mycalolide C [3]. The
      macrolide structures were elucidated by detailed analysis of their spectroscopic
      data and by comparison with related compounds.

PMID- 7561904
TI  - Sinugibberol, a new cytotoxic cembranoid diterpene from the soft coral Sinularia
      gibberosa.
AB  - Bioactivity-guided fractionation of a chloroform extract of the soft coral
      Simularia gibberosa afforded a new cytotoxic cembranoid diterpene, sinugibberol
      [1]. The structure of 1 was determined by spectral and X-ray crystallographic
      analysis.

PMID- 7561905
TI  - Sesquiterpene/quinol from a New Zealand liverwort, Riccardia crassa.
AB  - A new sesquiterpene/quinol, with mild cytotoxic and antibacterial activity, has
      been isolated from a New Zealand collection of the liverwort Riccardia crassa.
      The structure of this compound, riccardiphenol C [3], was established by nmr
      spectroscopy. Closely related compounds previously isolated from a Japanese
      collection of R. crassa were not detected in this collection.

PMID- 7561906
TI  - Biosynthesis of brominated tyrosine metabolites by Aplysina fistularis.
AB  - The biosynthesis of brominated tyrosine metabolites by the marine sponge Aplysina
      fistularis was investigated. [U-14C]-L-Tyrosine, [U-14C]-L-3-bromotyrosine, and
      [U-14C]-L-3,5-dibromotyrosine were incorporated into both dibromoverongiaquinol
      [1] and aeroplysinin-1 [2], and [methyl-14C]methionine was specifically
      incorporated into the O-methyl group group of 2. [Methyl-14C]-L-O-methyltyrosine,
      [methyl-14C]-L-3,5-dibromo-O-methyltyrosine, and several putative nitrile
      precursors were not incorporated into 1 or 2.

PMID- 7561907
TI  - Barceloneic acid A, a new farnesyl-protein transferase inhibitor from a Phoma
      species.
AB  - Three new diphenyl ethers, barceloneic acids A, B, and barceloneic lactone [1, 2,
      and 3, respectively] were isolated from a fermentation extract of a fungus of the
      genus Phoma. The structures of compounds 1-3 were determined by a combination of
      spectroscopic and single-crystal X-ray diffraction methods. The effect of these
      compounds on the inhibition of farnesyl-protein transferase (FPTase) was
      evaluated and results are presented. Barceloneic acid A [1] is a novel and modest
      inhibitor of FPTase with an IC50 value of 40 microM.

PMID- 7561908
TI  - The structures of new lanostane triterpenes from the fruiting bodies of Hebeloma
      senescens.
AB  - Three new lanostane triterpenes, hebelomic acids B[4], E[5], and F[6], were
      isolated from the inedible mushroom Hebeloma senescens. The latter two compounds
      are acyl derivatives of the new triterpene senescensol (12-deoxycrustulinol)
      [12]. The structures of compounds 4-6, including the absolute configuration of
      the 3-hydroxy-3-methylglutaric acid moiety, were established on the basis of
      spectral and chemical evidence.

PMID- 7561909
TI  - Persistent vegetative state.

PMID- 7561910
TI  - Cerebrospinal fluid.

PMID- 7561911
TI  - Spinal cord schwannoma after vertebral trauma: a causal relation?

PMID- 7561913
TI  - Convallari majalis (lily of the valley) (also known as Our Lady's tears, ladder
      to heaven).

PMID- 7561912
TI  - Changes in cerebral oxygen consumption are independent of changes in body oxygen
      consumption after severe head injury in childhood.
AB  - This study examines the relation between cerebral O2 consumption (CMRO2) and the
      O2 consumption of the rest of the body (BVO2) after severe head injury. Seventy
      nine serial measurements of whole body O2 consumption, CMRO2, plasma adrenaline,
      T3, and glucagon concentrations were made in 15 children with severe head
      injuries receiving neurointensive care. Body O2 consumption was measured with
      indirect calorimetry and CMRO2 with the Kety-Schmidt technique. There was no
      evidence of a significant relation between CMRO2 and BVO2. Within each child
      there were statistically significant positive relations between BVO2 and
      adrenaline, T3, and glucagon. By contrast, there was only a weak significant
      positive relation between CMRO2 and T3. In conclusion, CMRO2 and BVO2 seem to be
      determined independently after severe head injury. Thus therapeutic measures
      aiming to reduce CMRO2 need to be specific to the brain and it should not be
      assumed that measures which decrease whole body energy expenditure will
      necessarily have the same effect on CMRO2.

PMID- 7561914
TI  - Cerebral perfusion and psychometric testing in military amateur boxers and
      controls.
AB  - The objective was to compare two neurophysiological variables in active amateur
      boxers with non-boxing sportsmen. 41 boxers and 27 controls were given
      psychometric tests: 34 boxers and 34 controls underwent technetium-99m
      hexamethylpropyleneamineoxime single photon emission computerised tomography (Tc
      99m HMPAO SPECT) cerebral perfusion scans. The controls performed better at most
      aspects of the psychometric tests. Boxers who had fought fewer bouts had a
      tendency to perform better at psychometric tests than those boxers who had fought
      more bouts. Tc-99m HMPAO SPECT cerebral perfusion scanning showed that controls
      had less aberrations in cerebral perfusion than the boxers. In conclusion,
      significant differences were shown in two neurophysiological variables between
      young amateur sportsmen who box and those who do not. The long term effects of
      these findings remain unknown.

PMID- 7561915
TI  - Mild head injury in preschool children: evidence that it can be associated with a
      persisting cognitive defect.
AB  - This study describes the effect of mild head injury in preschool children on
      aspects of their cognitive performance in the year after injury and at the age of
      6.5 years, with particular reference to the development of reading skills. Mild
      head injury was defined by diagnosis at a hospital emergency department of a head
      injury which was not severe enough to need admission for observation. Seventy
      eight such children were compared with a group of 86 with a minor injury
      elsewhere. The groups had similar developmental, family, and socioeconomic
      status. There were no differences in cognitive tests soon after the injury, but
      at six months and one year children with mild head injury scored less than
      controls on one test, solving a visual puzzle (visual closure); they were also
      more likely to have had another mild head injury. At 6.5 years of age they still
      scored less than controls, reading ability was related to their visual closure
      score at one year, and they were more likely to have needed help with reading.
      Mild head injury seems to be able to produce subtle but significant changes which
      can affect school performance.

PMID- 7561916
TI  - Raised plasma arginine vasopressin concentrations during cluster headache
      attacks.
AB  - To obtain data about peripheral concentrations of arginine vasopressin in head
      pain syndromes, the plasma arginine vasopressin secretory pattern in 12 adult
      male patients with cluster headache was evaluated. Blood samples for plasma
      arginine vasopressin and osmolality determinations were collected before, and at
      15, 30, 45, 60, 90, and 120 minutes during a cluster attack. Blood pressure was
      also monitored. The same sampling was repeated during an asymptomatic period.
      During cluster attacks, the mean values of plasma arginine vasopressin before an
      attack (2.3 (0.1) ng/l) significantly increased, reaching their peak at 45
      minutes (4.8 (0.5) ng/l; P < 0.01 v baseline). No significant variations were
      found in mean arterial pressure and plasma osmolality. These data suggested
      involvement of neurotransmitter mechanisms regulating arginine vasopressin
      secretion and a possible role of arginine vasopressin in vasomotor phenomena
      accompanying cluster attacks.

PMID- 7561917
TI  - High resolution magnetic resonance imaging in adults with partial or secondary
      generalised epilepsy attending a tertiary referral unit.
AB  - In the past the underlying structural abnormalities leading to the development of
      chronic seizure disorders have usually only been disclosed by histological
      examination of surgical or postmortem material, due to their often subtle nature
      that was beyond the resolution of CT or early MRI. The MRI findings in 341
      patients with chronic, refractory epilepsy attending The National Hospital for
      Neurology and Neurosurgery and Chalfont Centre for Epilepsy are reported. Studies
      were performed on a 1.5 Tesla scanner with a specific volumetric protocol,
      allowing the reconstruction of 1.5 mm contiguous slices throughout the whole
      brain. Direct visual inspection of the two dimensional images without the use of
      additional quantitative measures showed that 254/341 (74%) were abnormal. Twenty
      four (7%) patients had more than one lesion. The principal MRI diagnoses were
      hippocampal asymmetry (32%), cortical dysgenesis (12%), tumour (12%), and
      vascular malformation (8%). Pathological confirmation was available from surgical
      specimens in 70 patients and showed a very high degree of sensitivity and
      specificity for the different entities. The advent of more widely available high
      resolution MRI should make it possible to identify the underlying pathological
      substrate in most patients with chronic partial epilepsy. This will allow a
      fundamental reclassification of the epilepsies for both medical and surgical
      management, with increasing precision as new methods (both of acquisition and
      postprocessing) are added to the neuroimaging battery used in clinical practice.

PMID- 7561918
TI  - Kallikrein-kinin system in chronic subdural haematomas: its roles in vascular
      permeability and regulation of fibrinolysis and coagulation.
AB  - The kallikrein-kinin system is closely related to both fibrinolysis and
      coagulation, and bradykinin--the end product of this system--is a powerful
      mediator which increases vascular permeability. In the present study, to test the
      hypothesis that the kallikrein-kinin system plays a part in the aetiology of
      chronic subdural haematomas, components of this system (prekallikrein, high
      molecular weight kininogen (HMW-kininogen), and bradykinin), and those of the
      fibrinolytic and coagulation systems were measured at 134 haematoma sites in 119
      patients. The activities of prekallikrein and HMW-kininogen in the haematomas
      were significantly lower than those in the plasma of the patients, and showed a
      parallel decrease. The bradykinin concentration in the haematomas was
      significantly higher than that in the plasma. These results indicate activation
      of the kallikrein-kinin system in chronic subdural haematomas. The activation of
      both fibrinolysis and coagulation was also shown, and there was a significant
      correlation between HMW-kininogen and plasminogen, fibrin/fibrinogen degradation
      products, or platelets in the haematomas. This suggests regulation of
      fibrinolysis and coagulation by the kallikrein-kinin system or mutual stimulation
      of these systems. In the outer membrane, perivascular haemorrhage, interstitial
      oedema, and leucocyte migration were evident microscopically, indicating an
      increase in vascular permeability. The protein concentration in the haematomas
      was significantly higher than that in the peripheral blood, indicating plasma
      exudation from the capillaries in the outer membrane. The activation of the
      kallikrein-kinin system, by increasing vascular permeability, may cause blood
      extravasation and plasma exudation from the capillaries into both the outer
      membrane and the haematoma cavity, resulting in enlargement of the haematoma.

PMID- 7561920
TI  - Hereditary myokymia and paroxysmal ataxia linked to chromosome 12 is responsive
      to acetazolamide.
AB  - A sixth family with autosomal dominantly inherited myokymia and paroxysmal ataxia
      is described. The syndrome in this family is linked to the recently discovered
      locus for inherited myokymia and paroxysmal ataxia on the human chromosome 12p,
      and a missense mutation is shown in the KCNA1 gene. The attacks of ataxia in this
      family compare well with those of previously described families and similarly are
      precipitated by kinesigenic stimuli, exertion, and startle. Responsiveness of
      these attacks to low dose acetazolamide is confirmed, but some loss of efficacy
      occurs with prolonged treatment, and side effects are notable. Although not all
      affected family members showed myokymia on clinical examination, electromyography
      invariably showed myokymic discharges, in one patient only after a short
      provocation with regional ischaemia. One affected family member also had attacks
      of paroxysmal kinesigenic choreoathetosis, responsive to carbamazepine.

PMID- 7561919
TI  - Spastic tetraplegia as an initial manifestation of familial Alzheimer's disease.
AB  - Two sisters with familial Alzheimer's disease developed spastic gait disturbance
      as an initial manifestation. Their gait disturbance progressed gradually,
      followed by dementia a few years later. Post-mortem examination of one of the
      patients disclosed degeneration of the thalamus and corticospinal tract in
      addition to numerous senile plaques and neurofibrillary tangles in the neocortex,
      both of which were confirmed by immunohistochemistry. This is the first report in
      which clinicopathological evaluation is sufficient to establish a new variant of
      Alzheimer's disease presenting initially as spastic tetraplegia.

PMID- 7561921
TI  - Psychogenic movement disorders: frequency, clinical profile, and characteristics.
AB  - Of 842 consecutive patients with movement disorders seen over a 71 month period,
      28 (3.3%) were diagnosed as having a documented or clinically established
      psychogenic movement disorder. Tremor was most common (50%) followed by dystonia,
      myoclonus, and parkinsonism. Clinical descriptions of various types are reviewed.
      Clinical characteristics common in these patients included distractability (86%),
      abrupt onset (54%), and selective disabilities (39%). Distractability seems to be
      most important in tremor and least important in dystonia. Other diagnostic clues
      included entrainment of tremor to the frequency of repetitive movements of
      another limb, fatigue of tremor, stimulus sensitivity, and previous history of
      psychogenic illness. On examination, 71% had other psychogenic features. Over 60%
      had a clear history of a precipitating event and secondary gain and 50% had a
      psychiatric diagnosis (usually depression). Twenty five per cent of patients
      presented with combined psychogenic movement disorder and organic movement
      disorder; 35% resolved and this subgroup had a shorter duration of disease than
      those who are unresolved. Psychogenic movement disorder represents an uncommon
      diagnosis among patients with movement disorders. The ability to make a diagnosis
      rests on the presence of a multitude of clinical clues and therapeutic action
      should be taken as early as possible.

PMID- 7561923
TI  - Progression of atrophy of the corpus callosum with deterioration of cerebral
      cortical oxygen metabolism after carotid artery occlusion: a follow up study with
      MRI and PET.
AB  - In cerebrovascular disease, progression of brain atrophy may reflect an increase
      in ischaemic changes. The purpose of this study was to determine whether atrophy
      of the corpus callosum progresses in association with a deterioration in cerebral
      cortical oxygen metabolism after occlusion of the carotid artery. Magnetic
      resonance imaging and PET were used to serially evaluate six patients with
      occlusion of the unilateral internal carotid artery at intervals ranging from 12
      to 50 months. One patient had no symptoms, one had a transient ischaemic attack,
      and four had a minor stroke. All patients had presented at most only subcortical
      lesions at the first evaluation. During follow up, no patient showed extension of
      subcortical lesions or recurrent stroke. The initial total callosal area:skull
      area ratio for the patients was significantly less than that for 14 age matched
      normal control subjects. The yearly decrease of callosal size in the patients,
      which differed significantly from zero and exceeded that in the controls, was
      significantly correlated with the deterioration in mean cerebral cortical oxygen
      metabolism. Three of the four patients who showed significant progression of
      callosal atrophy presented deterioration in haemodynamic states as well. It is
      concluded that in some patients atrophy of the corpus callosum progresses after
      occlusion of the carotid artery even in the absence of any overt episode of
      stroke, and that this atrophy is associated with deterioration in cerebral
      cortical oxygen metabolism. An increase in cerebral morphological changes with
      deterioration in cerebral metabolism related to ischaemia may occur after
      occlusion of the carotid artery, even in the absence of symptoms.

PMID- 7561922
TI  - Prognostic indicators in a range of astrocytic tumours: an immunohistochemical
      study with Ki-67 and p53 antibodies.
AB  - The treatment and prognosis of patients with cerebral astrocytic tumours are
      currently guided by histopathological classification. This study evaluates
      immunohistochemistry using Ki-67, an antibody to a nuclear protein expressed in
      proliferating cells, and DO-7, an antibody to the product of the tumour
      suppressor gene p53, as prognostic indicators for these tumours.
      Immunohistochemistry with Ki-67 has been correlated with the behaviour of many
      different tumours, but its value as a prognostic indicator in astrocytic tumours
      is diminished by the conflicting results of previous studies.
      Immunohistochemistry with antibodies to the p53 protein has been used as a
      prognostic indicator in melanomas and some carcinomas, but the relation between
      prognosis and accumulation of this protein in astrocytic tumours has not been
      clarified. We have tested the hypothesis that survival is correlated with Ki-67
      immunolabelling indices (LIs) and patterns of p53 immunolabelling in the cerebral
      astrocytic tumours of a large cohort of patients (n = 123) for whom clinical
      indices were well documented. Astrocytic tumours were divided into three
      histological types: fibrillary astrocytoma (n = 24), anaplastic astrocytoma (n =
      31), and glioblastoma (n = 68). Histological type and patient age were
      independent predictors of survival. Median Ki-67 LIs differed significantly (P <
      0.0001) between the types of astrocytic tumour, and tumours with a Ki-67 LI < 2%
      had a significantly (P < 0.0001) better prognosis. Ki-67 LI as a continuous
      variable carried a significant (P = 0.0043) unadjusted hazard to survival which
      was lost when adjusted for other variables, notably histological type. By
      contrast, no relation was found between survival and three categories of p53
      labeling (p53-negative, p53 LI < 40%, and p53 LI > 60%). The results indicate
      that, whereas Ki-67 immunohistochemistry predicts survival in patients with
      astrocytic tumours, conventional histological appraisal remains the best guide to
      prognosis, and immunohistochemistry for p53 has no value in the assessment of
      these tumours.

PMID- 7561924
TI  - Increased interictal cerebral glucose metabolism in a cortical-subcortical
      network in drug naive patients with cryptogenic temporal lobe epilepsy.
AB  - Positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) has
      been used to assess the pattern of cerebral metabolism in different types of
      epilepsies. However, PET with [18F]FDG has never been used to evaluate drug naive
      patients with cryptogenic temporal lobe epilepsy, in whom the mechanism of origin
      and diffusion of the epileptic discharge may differ from that underlying other
      epilepsies. In a group of patients with cryptogenic temporal lobe epilepsy, never
      treated with antiepileptic drugs, evidence has been found of significant
      interictal glucose hypermetabolism in a bilateral neural network including the
      temporal lobes, thalami, basal ganglia, and cingular cortices. The metabolism in
      these areas and frontal lateral cortex enables the correct classification of all
      patients with temporal lobe epilepsy and controls by discriminant function
      analysis. Other cortical areas--namely, frontal basal and lateral, temporal
      mesial, and cerebellar cortices--had bilateral increases of glucose metabolism
      ranging from 10 to 15% of normal controls, although lacking stringent statistical
      significance. This metabolic pattern could represent a pathophysiological state
      of hyperactivity predisposing to epileptic discharge generation or diffusion, or
      else a network of inhibitory circuits activated to prevent the diffusion of the
      epileptic discharge.

PMID- 7561925
TI  - Non-progressive familial idiopathic intracranial calcification: a family report.
AB  - The clinical features and long term outcome of familial idiopathic intracranial
      calcification in three members of one family are described. The illness presented
      as psychiatric disorder in all patients, and in one patient, epilepsy and
      intellectual deterioration were later manifestations. Skull radiographs and CT
      were performed sequentially, in one patient, over a 22 year period and, in
      another, CT was carried out eight years apart. In neither patient was there any
      evidence of progression of calcification.

PMID- 7561926
TI  - Chronic hypertrophic cranial pachymeningitis associated with HTLV-I infection.
AB  - Two patients presenting with recurrent multiple cranial neuropathy showed diffuse
      thickening and gadolinium enhancement of the dura mater on brain MRI. Both had
      anti-HTLV-I antibodies in serum. A quantitative polymerase chain reaction study
      of the peripheral blood disclosed that the HTLV-I proviral DNA loads increased
      considerably in one case and moderately in the other. Both showed a spontaneous
      proliferation of peripheral blood lymphocytes as well as an increase in
      helper/inducer T cells. Neither had any other underlying infections or autoimmune
      diseases. Thus it is possible that hypertrophic pachymeningitis developed as a
      result of multiorgan involvement of HTLV-I infection in these patients.

PMID- 7561927
TI  - Thalamo-olivary degeneration in a patient with laryngopharyngeal dystonia.
AB  - A 67 year old woman with a two year history of laryngopharyngeal dystonia,
      spasmodic dysphonia, and parkinsonism succumbed to Wernicke's encephalopathy and
      died six months later. Necropsy showed, besides Wernicke's encephalopathy,
      degenerative changes in selected thalamic nuclei (dorsomedial, pulvinar, and the
      medial geniculate bodies) and the inferior olives and numerous cerebellar
      torpedoes. The substantia nigra and basal ganglia were spared. Immunostaining for
      prion protein was negative. This patient indicated a new type of presentation of
      so-called pure thalamic degeneration, or more precisely thalamo-olivary
      degeneration.

PMID- 7561929
TI  - More doctors.

PMID- 7561928
TI  - Management of spontaneous extramedullary spinal haematomas: results in eight
      patients after MRI diagnosis and surgical decompression.
AB  - Spinal cord compression due to extradural and subdural haemorrhage is a
      neurosurgical emergency. Differences in clinical presentation in relation to
      localisation of the haematoma, value of MRI as a diagnostic tool, surgical
      treatment, and prognosis were investigated in a retrospective case series of
      eight patients with extradural (n = four) and subdural (n = four) haematomas.
      Results of MRI were compared with operative findings and proved to be of high
      sensitivity in defining the type of bleeding and delineating craniocaudal
      extension and ventrodorsal location. Surgical treatment by decompressive
      laminectomy, haematoma evacuation, and postoperative high dose corticosteroids
      resulted in resolution of symptoms in five patients and improvement in the
      clinical situation in two patients. One patient with a chronic subdural haematoma
      had a second operation because of arachnoidal adhesions. One patient presented
      with a complete cord transection syndrome due to an acute subdural haematoma and
      remained paraplegic. It is concluded that prompt, reliable, and non-invasive
      diagnosis by MRI leads to efficient surgical treatment and a favourable outcome
      in this rare condition.

PMID- 7561930
TI  - Improvement of Isaacs' syndrome after treatment with azathioprine.

PMID- 7561931
TI  - Hypomania after temporal lobectomy: a sequela to the increased excitability of
      the residual temporal lobe?

PMID- 7561932
TI  - Machado-Joseph disease mutations as the genetic basis of most spinocerebellar
      ataxias in Germany.

PMID- 7561933
TI  - Oculographic findings in traumatic unconsciousness: prognostic implications.

PMID- 7561935
TI  - Delayed ischaemia after subarachnoid haemorrhage: a role for small vessel
      changes.

PMID- 7561936
TI  - Neurosyphilis presenting with dissociative symptoms.

PMID- 7561934
TI  - Limbic system dysfunction in Alzheimer's disease.

PMID- 7561937
TI  - Alternating paroxysmal dystonia and hemiplegia in childhood as a symptom of basal
      ganglia disease.

PMID- 7561938
TI  - Functional brain imaging.

PMID- 7561939
TI  - Duchenne-like myopathy in double-mutant mdx mice expressing exaggerated mast cell
      activity.
AB  - Dystrophin-deficient female mdx mice were bred with male Tsk+/+ pa mice to
      examine the role played by mast cells in the pathophysiology of dystrophin
      deficiency. Resultant mdx/Tsk double-mutant mice were then examined functionally,
      biochemically, and histologically. While mdx mice remained as strong as their
      normal counterparts, mdx/Tsk double-mutant mice became progressively weak with
      age. Serum creatine kinase activity was significantly elevated in both mdx and
      mdx/Tsk double-mutant mice over normal controls. However, mast cell-derived
      plasma tryptase activity was consistently higher in the double-mutant than in mdx
      mice. In addition, histological examination of gastrocnemius muscle revealed that
      while necrosis was persistent in both strains of mdx mice from 2 to 8 weeks of
      age, regeneration was significantly reduced in the double-mutant mice. Of
      particular interest was the fact that necrosis in the mdx/Tsk double mutant
      exceeded mdx values at 8 weeks of age, corresponding approximately with a second
      peak in tryptase activity. Therefore, heightened mast cell activity appears to
      elicit in the dystrophin-deficient mdx mouse a myopathy not unlike the human
      Duchenne disease.

PMID- 7561941
TI  - Successful plasmapheresis in Bickerstaff's brain stem encephalitis associated
      with anti-GQ1b antibody.
AB  - Patients with Guillain-Barre syndrome (GBS) and Fisher's syndrome (FS) benefit
      from plasmapheresis. Specific treatments, however, have yet to be established for
      Bickerstaff's brain stem encephalitis (BBE). We showed earlier that sera from BBE
      patients, as well as from patients with FS and GBS with ophthalmoplegia, have
      autoantibody to GQ1b ganglioside in the acute phase of the disease. We report 2
      BBE patients who had high IgG anti-GQ1b antibody titers and were treated
      successfully with plasmapheresis.

PMID- 7561940
TI  - Activated sialidase activity in transformed lymphocytes by Epstein-Barr (EB)
      virus of sialidosis type I (cherry-red spot-myoclonus syndrome).
AB  - We report a new Japanese family of sialidosis type I. The sialidase activity was
      deficient in the lymphocytes of 2 patients (6.8% (sister) and 12.5% (brother) of
      control mean). However, surprisingly, using the transformed lymphocytes by EB
      virus, this activity was activated to 51.7% (sister) and 49.5% (brother) of
      control mean, respectively. Although the mechanism for this activation was not
      known, we discussed the possible mechanisms for this phenomenon.

PMID- 7561942
TI  - Time-trend analysis of mortality from malignant tumors of the nervous system in
      Spain, 1952-1986.
AB  - We analyzed time trends in mortality from malignant tumors of the nervous system
      (MTNS) in the adult Spanish population during the period 1952-1986, using Poisson
      regression analysis of age at death, year of birth and year of death. During such
      period, mortality rose especially in the elderly as well as among young and
      middle-aged men. We found two modest period effects, in both sexes attributed to
      changes in certification practice. An ascending effect in cohorts born up to 1920
      in males and females was attributed to improvements in ascertainment. A positive,
      progressive, cohort effect in males born post-1920 was detected. Mortality from
      MTNS in Spain was medium-high with a tendency to rise, most likely due to
      improvements in diagnosis and registration. From this analysis, the existence of
      a true increase in incidence of brain glioma among young and middle-aged male
      adults during recent decades is suggested.

PMID- 7561943
TI  - Effect of hypoxemia and ethacrynic acid on ABR and distortion product emission
      thresholds.
AB  - Various studies have shown that induction of hypoxemia in animals such that
      arterial blood oxygen tensions reach 20-30 mm Hg is accompanied by reversible
      threshold elevations of the auditory nerve-brain-stem evoked response (ABR). In
      this state, the endocochlear potential (EP) is depressed, causing a smaller
      potential difference across the hair cells and/or reduced activity of the
      cochlear amplifier of the outer hair cells. In order to test these possibilities,
      ABR threshold (an expression of the overall sensitivity of the cochlea) and
      changes in threshold of the cubic (2f1-f2) distortion product emissions (DPE) (an
      expression of activity of the cochlear amplifier) were measured in the same cats
      while the EP was depressed by hypoxemia or by ethacrynic acid. During the
      episodes of hypoxemia, DPE thresholds were elevated by 10 dB while ABR thresholds
      were elevated by 22.8 dB. Therefore, it seems that a normal EP is necessary both
      for normal cochlear transduction (inner hair cells) and for normal cochlear
      amplification (outer hair cells). The human fetus in utero is relatively hypoxic
      and there is evidence that its auditory threshold is also similarly elevated.
      Therefore the threshold elevation in the fetus in utero, estimated to be about 20
      dB, is a consequence of both reduced transduction current through the inner hair
      cells (about 10 dB) and an additional 10 dB reduction in the activity of the
      cochlear amplifier of the outer hair cells.

PMID- 7561944
TI  - Progressive sensory-motor polyneuropathy with tomaculous changes is associated to
      17p11.2 deletion.
AB  - We examined for the presence of 17p11.2 deletion, by Southern blotting and
      fluorescent in situ hybridization, 3 cases with progressive sensory-motor
      polyneuropathy and diffuse tomaculous changes at sural nerve biopsy. We
      demonstrated in all the cases the 17p11.2 deletion, previously reported in
      hereditary neuropathy with pressure palsy, an inherited disorder of the
      peripheral nervous system with similar pathologic changes but a different
      clinical phenotype. The molecular study of the 17p11.2 region should be
      considered as a non invasive method for differential diagnosis in selected cases
      of progressive polyneuropathy.

PMID- 7561945
TI  - Familial spastic paraplegia with mental impairment and thin corpus callosum.
AB  - We described four patients in two families of unique familial spastic paraplegia
      (FSP) which was thought to be possibly autosomal recessive inheritance. All four
      patients had quite similar manifestations. Gait disturbance started at their
      second decade, then spastic paraparesis and mental deterioration progressed
      slowly. Cerebellar ataxia and sensory loss in the distal parts of four
      extremities were also slightly presented. In all patients, cranial MRI revealed
      marked thin corpus callosum with mild changes in the region of periventricular
      white matter and in the gray matter. Biopsied sural nerves of all patients showed
      chronic axonal degeneration with mild decrease of both large and small myelinated
      fibers. Electron microscopic study demonstrated crystalline-like inclusion bodies
      in the cytoplasm of Schwann cells in all patients. Despite extensive
      investigation for metabolic disorder, we could not find any abnormality. However
      an etiology have not established at the time presented, the combination of these
      clinical features suggested that the disorder could represent a specific clinical
      entity.

PMID- 7561946
TI  - Fractionation of visuoperceptual dysfunction in Parkinson's disease.
AB  - There is considerable evidence that visuoperceptual function is impaired in
      Parkinson's disease although this view remains contentious. The issue is
      confounded by studies which have demonstrated impairment of visual sensation, in
      particular high-contrast visual acuity, in Parkinson's disease. We have measured
      the visuoperceptual performance of 16 patients with mild to moderate Parkinson's
      disease, both on and off drugs, and 16 age and sex matched control subjects on
      non-motor tests of visual resolution, static perception, and dynamic perception.
      Performance on the perceptual tasks was measured in terms of perceptual
      resolutions and was found impaired in the parkinsonian group. After removal of
      the contribution of poorer visual resolution, the overall visual perception
      remained impaired, although to a relatively subtle degree, such that the
      difference between the two groups on its static and dynamic components did not
      reach significance.

PMID- 7561948
TI  - Molecular analysis of X-linked adrenoleukodystrophy patients.
AB  - A molecular analysis of 4 Japanese adrenoleukodystrophy (ALD) patients was
      carried out, according to the recently published report on ALD gene cDNA. In a
      Southern blot analysis, we were not able to detect a large deletion in all
      patients. In a Northern blot analysis, no mRNA was detected in one patient, while
      the others had normal mRNA in both size and amount. Three patients had missense
      mutations including; 534Pro-->Leu (1987C-->T), 660Arg-->Trp (2364C-->T), and
      512Gly-->Ser (1920G-->A), respectively. These mutations existed in the C-terminal
      region conserved in the ATP-binding cassette superfamily of transporters. In a
      Western blot analysis using polyclonal antibodies against the C-terminal peptide
      as well as the whole peptide of ALD protein, no 80 kDa protein was found in any
      of the 4 patients, which was observed in the control cells. The ALD protein in 3
      patients with a missense mutation might be degraded immediately after translation
      because of the unstable higher structure or by the disruption of the hitherto
      unknown targetting signal to the peroxisome. The molecular analysis of the ALD
      gene as done in this study is thus considered to be the first step to further
      elucidate the pathogenic mechanism of ALD.

PMID- 7561947
TI  - Elevated cerebrospinal fluid levels of manganese superoxide dismutase in
      bacterial meningitis.
AB  - We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD)
      in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated
      levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method,
      were more prominent than those in aseptic meningitis (AM) and encephalitis (EN).
      In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase
      and S-100b protein, which are markers of damages to nervous tissues, but did not
      with any of them in BM. CSF concentrations of tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1 alpha (IL-1 alpha) were higher in BM than in AM and EN.
      From the serial measurements in BM, the peak values of these cytokines
      chronologically preceded or corresponded to those of Mn SOD.
      Immunohistochemically, a large number of the glial cells were stained for Mn SOD
      in the cerebral cortex from a patient with BM. By contrast, in the normal
      cerebral cortex, the glial cells were negative for Mn SOD staining. These results
      suggest that the marked increase of Mn SOD in the CSF in BM may be related to the
      increase of such cytokines as TNF-alpha and IL-1 alpha and that these cytokines
      may play a role in the induction of Mn SOD in nervous tissues.

PMID- 7561949
TI  - Comparison of cathepsin protease activities in brain tissue from normal cases and
      cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and
      Huntington's disease.
AB  - Recent evidence, based upon immunocytochemical and histochemical analysis of
      brain cortical tissue from alzheimer's disease patients, has suggested that
      altered activity and/or distribution of the lysosomal proteases cathepsins B and
      D may be implicated in the abnormal protein processing pathway resulting in
      formation of the neurotoxic amyloid A4 peptide, characteristic of this
      neurodegenerative disorder. We have therefore compared, via biochemical assay
      techniques using conventional or specially synthesised (corresponding to protein
      cleavage points of relevant to A4 peptide formation) fluorogenic substrates, the
      levels of activity of the lysosomal proteases cathepsins B, D, H and L, and
      dipeptidyl aminopeptidases I and II in frontal cortex (grey/white matter) from
      control and Alzheimer's disease patients. For comparative purposes, activity
      levels of the above enzymes were also determined in frontal cortex tissue from
      cases with Lewy body dementia and Parkinson's disease, and in caudate tissue from
      control and Huntington's disease cases. There was no significant difference in
      activity for any protease types in tissue from control cases and cases with
      Alzheimer's disease, Lewy body dementia or Parkinson's disease, with the
      exception of reduced dipeptidyl aminopeptidase II activity in Lewy body dementia
      and Parkinson's cases. We have therefore been unable to confirm a potential role
      for lysosomal cathepsins in the characteristic neurodegeneration associated with
      Alzheimer's disease; however the finding of significant increases in activity of
      dipeptidyl aminopeptidase II, cathepsin H and cathepsin D specifically in cases
      with Huntington's disease is of particular note. We therefore suggest the
      potential role of the latter enzymes in the pathogenesis of Huntington's disease
      requires further investigation.

PMID- 7561950
TI  - Increased cathepsin B activity in multiple sclerosis brain.
AB  - Cathepsin B (CB) activity was measured in aqueous extracts of frozen autopsy
      specimens of centrum semiovale from three MS patients, five control patients with
      other neurological diseases, and five normal individuals. Mean activity was
      significantly increased in the MS tissue compared with controls. The mean
      activity in MS tissue containing demyelinating lesions was higher than that in
      normal appearing white matter which was higher than that in normal control
      specimens but the differences were not statistically significant. The mean CB
      activity in patients with other neurological diseases was higher than normal
      control activity and, although the difference was not statistically significant,
      this observation suggests that increases in CB may not be specific for MS.
      Immunohistochemical studies of the MS brain tissue analyzed biochemically
      suggested that monocytes, macrophages and reactive astrocytes are potential
      sources of increased CB in MS brain.

PMID- 7561951
TI  - Serial magnetic resonance imaging in post-infectious focal encephalitis due to
      influenza virus.
AB  - Two cases of a 13-year-old girl and a 14-year-old boy with postinfectious focal
      encephalitis due to influenza are reported. The clinical and magnetic resonance
      imaging (MRI) findings included: (1) partial motor seizures as the initial
      central nervous system manifestation, appearing more than 20 days after the
      influenzal infection, (2) no change in the level of consciousness although a boy
      demonstrated apraxia, and (3) high signal intensity lesions noticed with T2
      weighted MRI located mainly in the cortex. The girl's lesion appeared to resolve
      within 10 days on MRI, while that of the boy (demonstrated in the thalamus on a
      third MRI) resolved within 1 week. However, a new lesion appeared in the cortex
      approximately 1 month later, that was visualized on a fourth MRI. Small
      gadolinium-enhanced lesions also were noticed during earlier stages in both
      patients. The pathogenesis of these MRI lesions is unknown, but the coexistence
      of small enhancing lesions, rapidly resolving lesions, and the elevated thrombin
      anti-thrombin III complexes, may indicate the presence of an angiopathy. Serial
      MRI examinations in patients with postinfectious encephalitis may lead to a
      better understanding of the pathogenesis of this disorder.

PMID- 7561952
TI  - Kearns-Sayre syndrome associated with mitochondrial DNA deletion or duplication:
      a molecular genetic and pathological study.
AB  - The neuropathological findings in 2 patients with Kearns-Sayre syndrome and
      mitochondrial DNA (mtDNA) rearrangements, one a predominant deletion and the
      other a predominant duplication, were remarkably similar, showing diffuse
      vacuolation of white matter. There were some of the pathological features of
      Leigh's syndrome in the spinal cord of the patient with a duplication. In the
      patient with a predominant deletion, rearranged mtDNA was undetectable in blood,
      spleen, and testis, and present in highest amounts in muscle and the brain, but
      relatively low in cerebellum, reflecting the ratio seen, albeit in much smaller
      amounts, in normal aged brains. MtDNA rearrangements in this patient were largely
      deletions or deletion dimers; duplicated mtDNA was present in only trace amounts
      in some tissues and there was none in skeletal muscle. The patient with a
      predominant duplication of mtDNA had higher amounts of rearranged mtDNA in blood
      (mainly duplicated) than muscle (mainly deleted). Correlation of these data with
      tissue dysfunction is probably complicated by the replicative behaviour of
      deleted, duplicated and normal mtDNA.

PMID- 7561953
TI  - A comparison between the stimulated and paroxysmal release of endogenous amino
      acids from rat cerebellar, striatal and hippocampal slices: a manifestation of
      spreading depression?
AB  - Spreading depression, which can be evoked by a variety of stimuli both in vitro
      and in vivo, is associated with profound changes in extracellular ion
      concentrations and enhanced release of neurotransmitter amino acids. We have
      observed a transient spontaneous release of amino acids in slice preparations
      obtained from rat cerebellum, striatum and hippocampus; this phenomenon has
      similar properties to stimulus-evoked spreading depression. Aspartate, glutamate,
      glutamine, serine, glycine and gamma-aminobutyric acid (GABA) release were
      potentiated during these episodes in all three brain regions, with a variable
      effect upon taurine release. When compared to glutamate release, a consistently
      high release of aspartate, glycine and serine was observed. Amino acid release,
      evoked by whole slice depolarization using veratridine (10-25 microM) or elevated
      potassium (35-60 mM) consistently enhanced glutamate release, and to a lesser
      extent aspartate release, but had negligible effect upon the other amino acids.
      Thus, the release profiles for spontaneous and depolarization-evoked release are
      markedly different. We suggest that the spontaneous release observed in brain
      slices represents a spreading depression-like phenomenon; the putative roles of
      the amino acids are discussed.

PMID- 7561954
TI  - A new familial congenital myopathy in children with desmin and dystrophin
      reacting plaques.
AB  - In 5 children with a progressive congenital myopathy representing 3 different
      families, unusual histological, immunohistochemical and ultrastructural changes
      in skeletal muscle have been found. Histologically, this myopathy was
      characterized by the presence of fine hyaline plaques devoid of oxidative as well
      as ATPase enzyme activities. At the ultrastructural level plaques were composed
      of helical filaments and amorphous dense material. Helical filament storage
      corresponded to strong desmin as well as ubiquitin immunoreactivity. In addition
      they were also dystrophin positive. The exclusive appearance of desmin, ubiquitin
      and dystrophin positive plaques in muscle specimens from 5 children emphasize the
      uniqueness of these plaques as well as this special form of a congenital
      myopathy.

PMID- 7561955
TI  - Genetic susceptibility to multiple sclerosis may be linked to polymorphism of the
      myelin basic protein gene.
AB  - The present paper compares the genetic polymorphism of a part of the myelin basic
      protein (MBP) gene in 64 Danish MS patients with that of 57 normal controls. PCR
      analysis, using primers flanking the 5' area from 479 to 1812 bp upstream the
      initiator methionine in the MBP gene, revealed that genetic susceptibility to MS
      is linked to polymorphism in the part of the MBP gene studied. Thus we found
      three different band patterns i.e. a homozygote with a 1445 bp long fragment, a
      homozygote with a fragment 1318 bp long and a heterozygote with both bands
      present. 59% of 64 patients with MS were homozygous for 1.445 kb allele, versus
      40% of 57 control subjects, 18% of the control subjects were homozygous for the
      1.318 kb, while only 0.7% of the MS patients possessed this allele. The
      differences between incidence of the three band pattern in the MS and the control
      group were significant at 1% level. Validation analysis furthermore support, the
      view that the 1445 bp PCR fragment is associated with MS.

PMID- 7561957
TI  - Influence of peripheral nerve grafts on the expression of GAP-43 in regenerating
      retinal ganglion cells in adult hamsters.
AB  - We have examined the ability of axotomized retinal ganglion cells in adult
      hamsters, to regenerate axons into a peripheral nerve graft attached to the optic
      nerve and the expression of GAP-43 by these neurons. We also examined the effect
      on these events of transplanting a segment of peripheral nerve to the vitreous
      body. The left optic nerves in three groups of hamsters were replaced with a long
      segment of peripheral nerve attached to the proximal stump of the optic nerve
      approximately 2 mm from the optic disc to induce regeneration of retinal ganglion
      cells into the peripheral nerve. An additional segment of peripheral nerve was
      transplanted into the vitreous of the left eye in the second group. The animals
      from the first and second groups were allowed to survive for 1-8 weeks and the
      number of regenerating retinal ganglion cells was determined by applying the
      retrograde tracer, Fluoro-Gold to the peripheral nerve graft and the expression
      of GAP-43 was studied by immunocytochemistry in the same retinas. As a control, a
      segment of optic nerve was transplanted into the vitreous body of the left eye in
      the third group of hamsters. These animals were allowed to survive for 4 weeks
      and the number of regenerating retinal ganglion cells was counted as in Groups 1
      and 2. The percentages of the regenerating retinal ganglion cells which also
      expressed GAP-43 were very high at all time points in Group 1 (with no
      intravitreal peripheral nerve) and Group 2 (with intravitreal peripheral nerve)
      and at 4 weeks for the Group 3 (with intravitreal optic nerve) animals. In
      addition, the number of regenerating retinal ganglion cells, the number of
      retinal ganglion cells expressing GAP-43 and the number of regenerating retinal
      ganglion cells which also expressed GAP-43 were much higher in Group 2 than in
      Group 1 at all the time points and it was also much higher in Group 2 than in
      Group 3 at 4 weeks whereas there was no significant difference between the
      results from Groups 1 and 3 at 4 weeks. These data suggested that there was a
      close correlation between the number of the axotomized retinal ganglion cells
      regenerating axons into the peripheral nerve graft attached to the optic nerve
      and the expression of GAP-43.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7561956
TI  - Is dystrophin always altered in Becker muscular dystrophy patients?
AB  - The differential diagnosis between autosomal recessive limb-girdle (LGMD) and X
      linked Becker muscular dystrophy (BMD) is very important for genetic counseling.
      It has been hypothesized that all BMD patients would have dystrophin alterations
      and dystrophin analysis could identify the Xp21 MD. Qualitatively abnormal
      dystrophin is easily detectable, but it is generally associated with in-frame DNA
      deletions or duplications. In patients with no detectable DNA deletions, in which
      X-linked inheritance cannot be proved, dystrophin quantification is still the
      only available test for differential diagnosis. In order to assess the accuracy
      of dystrophin quantification test in delineating Becker patients, we analyzed
      dystrophin abundance in BMD patients with a positive history of X-linked
      inheritance and no DNA detectable mutation, as compared to patients from families
      with LGMD. We observed that patients from 2 among the 5 BMD families have nearly
      normal dystrophin, while alteration in dystrophin content was observed in
      patients from 2 among the 7 LGMD families studied (probably as a secondary effect
      of alteration in the whole dystrophin-glycoproteins complex). These results
      suggest that dystrophin quantification, as an isolated test is not helpful for
      differential diagnosis between BMD and LGMD.

PMID- 7561958
TI  - Morphological plasticity of axotomized retinal ganglion cells following
      intravitreal transplantation of a peripheral nerve segment.
AB  - During normal development of retinal ganglion cells when the axons are growing,
      transient dendritic spines have been observed. Similar dendritic spine-like
      processes are also exhibited by retinal ganglion cells undergoing axonal
      regeneration into a peripheral nerve grafted to the damaged optic axons. Here we
      show, using the intracellular injection of Lucifer Yellow, that when a segment of
      peripheral nerve is transplanted to the vitreous body, a procedure which induces
      ectopic sprouting of axon-like processes from the cell bodies and dendrites of
      some retinal ganglion cells, similar spine-like processes appear on the dendrites
      of cells with ectopic sprouts. Quantitative analysis indicated that there were
      significant changes with posttransplantation survival time in the distributions
      of spine-like processes and axon-like processes on these sprouting retinal
      ganglion cells following the intravitreal transplantation of a piece of
      peripheral nerve. The remodelling of the spine-like processes and axon-like
      processes correlated with one another suggesting that plastic changes can occur
      in certain dendritic subcompartments independent of the growth activity of the
      other dendritic subcompartments.

PMID- 7561959
TI  - Alterations of Muller (glial) cells in dystrophic retinae of RCS rats.
AB  - We have carried out a light microscopical study of Muller cells in the retinae of
      rats with inherited retinal dystrophy (Royal College of Surgeons rats). Isolated
      retinae of both control and Royal College of Surgeons rats were exposed to a
      Procion Yellow solution which is taken up selectively into Muller cells. The
      shape of the cells was then studied by confocal microscopy. Enzymatically
      isolated Muller cells were studied immunocytochemically with antibodies against
      glial fibrillary acidic protein, cathepsin D, beta-amyloid precursor protein, bcl
      2 protooncogene product, and glutamine synthetase. Muller cells from RCS retinae
      were shorter than those from control retinae, and showed a coarse hypertrophy of
      their distal (sclerad) processes. In Muller cells isolated from the retinae of
      Royal College of Surgeon's rats, the expression of glial fibrillary acidic
      protein, cathepsin D, beta-amyloid precursor protein and bcl-2 protooncogene
      product was increased, and the expression of glutamine synthetase was reduced.
      Obviously, loss of neighbouring neurons leads to major alterations of both the
      shape and metabolism of Muller cells. The expression of enzymes that serve
      functional glio-neuronal interactions, such as glutamine synthetase, seems to be
      down-regulated, whereas proteins involved in cell reconstruction (cathepsin D),
      cell repair (possibly beta-amyloid precursor protein), and protection against
      apoptotic cell death (bcl-2 protooncogene product), are up-regulated, together
      with the 'pathological marker' glial fibrillary acidic protein.

PMID- 7561960
TI  - Sprouting of non-sympathetic myelinated and unmyelinated fibres in response to
      chronic sympathetic denervation in the pineal gland of the Chinese hamster,
      Cricetulus griseus.
AB  - We have examined the effects of chronic sympathetic denervation on non
      sympathetic myelinated and unmyelinated fibres in the superficial pineal gland of
      the Chinese hamster (Cricetulus griseus), using LM, EM and immunohistochemistry.
      The results suggest that non-sympathetic, myelinated and unmyelinated fibres
      enter the superficial pineal gland at its distal portion by way of the nervi
      conarii, and that these fibres are immunoreactive for calcitonin gene-related
      peptide or substance P. Non-sympathetic, myelinated and unmyelinated fibres in
      the superficial pineal gland increased in number following chronic superior
      cervical ganglionectomy. The number of unmyelinated fibres in the nervi conarii
      also increased in ganglionectomized animals. Thus, the numerical increase of
      calcitonin gene-related peptide or substance P fibres found in the superficial
      pineal gland after long-term sympathectomy may be due to sprouting of these
      fibres. It is speculated that the growth of non-sympathetic, myelinated and
      unmyelinated fibres and myelination of the former fibres occurring after
      sympathectomy are caused by nerve growth factor-related mechanisms.

PMID- 7561961
TI  - Spongy degeneration in the zitter rat: ultrastructural and immunohistochemical
      studies.
AB  - Pathological changes in the grey matter of the zitter rat were examined by
      electron microscopy and immunohistochemistry to investigate the pathogenesis of
      spongy degeneration. Vacuole formation was first detected in the pons and the
      outer thalamus at 2 weeks of age. The vacuoles arose from the periaxonal or inter
      myelinic spaces as well as the cytoplasm of some oligodendrocytes or astrocytes.
      With increasing age, some dendrites and the cytoplasm of neurons developed an
      electron lucent area with sparse organelles and the vacuoles occasionally fused
      together. Although spongy degeneration gradually extended to the entire CNS, no
      inflammatory or phagocytotic cell infiltration and no viral particles were
      detected. Glial fibrillary acidic protein immunoreactivity increased transiently
      in the vacuolated areas from 2 to 15 weeks of age (maximal at 7 weeks of age).
      Although zitter rats older than 65 weeks showed some reactive astrocytes in
      vacuolated areas, their numbers and the intensity of immunostaining decreased
      with advanced vacuolation suggesting astrocytic hypofunction in response to
      tissue damage. Immunoreactivity for synaptophysin was weaker in the zitter rats
      than in the control rats throughout the observation period, which suggested that
      synapse formation was disturbed in the zitter rats, probably due to a combination
      of hypomyelination and vacuole formation in the grey matter. These findings
      suggest that an unknown genetic abnormality, probably related to cell membrane
      biosynthesis or cell-to-cell interactions, produces both hypomyelination and
      spongy degeneration in the zitter rat.

PMID- 7561962
TI  - Rasmussen's syndrome: pathogenetic theories and therapeutic strategies.

PMID- 7561963
TI  - Neuropsychological tests and [99mTc]-HM PAO SPECT in the diagnosis of Alzheimer's
      dementia.
AB  - Twenty-three patients with Alzheimer's dementia (AD) in relatively early stages
      and 40 patients with other cognitive disorders of vascular or degenerative
      aetiology underwent neuropsychological examination and [99mTc]-HM PAO single
      photon emission computed tomography (SPECT). In contrast to the commonly accepted
      notion of a posterior temporoparietal reduction of tracer uptake as the typical
      SPECT pattern of AD, the most consistent feature found in the SPECT images of our
      AD patients was a hippocampal uptake deficit, associated with a variable degree
      of temporal, parietal and frontal deficit (extending from the posterior to the
      anterior regions), according to the severity of the disease. These results
      support the theory of AD as a "hippocampal dementia", at least in the early
      stages. Neuropsychological tests were found to be somewhat more specific and more
      accurate than SPECT in distinguishing AD from non-AD cases.

PMID- 7561965
TI  - Subclinical autonomic disturbances in multiple sclerosis.
AB  - We compared results from non-invasive autonomic testing [sympathetic skin
      responses (SSR), heart beat variation during deep breathing, and orthostatic
      manoeuvre with transcranial Doppler monitoring in 22 patients] with motor and
      somatosensory evoked potentials (MEP and SEP) in 30 unselected patients with
      multiple sclerosis. We found a similarly high yield of pathological results for
      SSR, MEP and SEP (66.7%, 65.5%, and 69%, respectively). When analysed for each
      limb (n = 120), SSR were highly correlated with MEP and SEP (for both P < 0.001).
      Heart beat variation was reduced in only 3 patients. In 4 of 22 patients
      orthostatic manoeuvre induced a pathological decrease in cerebral blood flow
      velocity despite normal systemic blood pressure being maintained. We conclude
      that SSR may be a useful additional diagnostic tool in patients with multiple
      sclerosis. Cerebral dysautoregulation is a rather frequent finding, although its
      significance is not known.

PMID- 7561964
TI  - Effects of cueing on visuospatial processing in unilateral spatial neglect.
AB  - Patients with typical left unilateral spatial neglect bisected lines after cueing
      to the left end-point, the fixation point being monitored with an eye camera.
      They persisted with the point of initial fixation made after cueing and placed
      the mark there without searching leftwards again. The rightward shift of fixation
      to the initial point of fixation thus determined the location of the subjective
      midpoint. We consider that rightward attentional bias increased the amplitude of
      this shift that was planned on the basis of the perception of the whole line
      while cueing. This hypothesis may explain smaller but obvious rightward bisection
      errors found in the cueing condition.

PMID- 7561967
TI  - Gaze-evoked nystagmus and smooth pursuit deficits: their relationship studied in
      52 patients.
AB  - Gaze-evoked nystagmus occurs with cerebellar and brainstem lesions and reflects a
      deficiency of the so-called common neural integrator. Experimental data show that
      loss of the neural integrator also abolishes slow conjugate eye movements, i.e.
      smooth pursuit eye movements and the vestibulo-ocular reflex (VOR). Since the
      smooth pursuit system has its own premotor circuits, a smooth pursuit deficit can
      be either the result of a premotor smooth pursuit lesion or the consequence of a
      gaze-holding deficit. To study this question DC eye movement recordings of 52
      patients with horizontal gaze-evoked nystagmus and/or smooth pursuit deficits
      were studied in detail. It was found that the majority (71%) had a combined
      smooth pursuit and gaze-holding deficit. Thirteen patients (25%) had a smooth
      pursuit deficit only. Only 2 patients (4%) had an isolated gaze-evoked nystagmus,
      which was comparatively weak. Thus a major finding is that each substantial gaze
      evoked nystagmus is combined with a smooth pursuit deficit; the two deficits are
      well correlated (coefficient r = 0.81). In all patients with a smooth pursuit
      deficit, visual suppression of the VOR was similarly impaired, when comparing the
      groups with and without gaze-evoked nystagmus. It is argued here that, although
      gaze-holding and smooth pursuit deficits are well correlated, the gaze-holding
      deficits seen in patients are not severe enough to explain the smooth pursuit
      deficit solely as a consequence of the gaze-holding deficit. Rather it probably
      reflects the close anatomical vicinity of gaze-holding and smooth pursuit
      mechanisms in the floccular region, the vestibular nuclei/nucleus prepositus
      complex and its connecting pathways.

PMID- 7561966
TI  - Postzygotic instability of the myotonic dystrophy p[AGC] in repeat supported by
      larger expansions in muscle and reduced amplifications in sperm.
AB  - We have analysed the [AGC] expansion in leucocytes, muscle and sperm from 17
      individuals affected by myotonic dystrophy (DM). Skeletal muscle showed a larger
      repeat number than leucocytes in the same patient. A similar degree of expansion
      was detected in differently affected muscles of a single patient. The germline
      mutation (< or = 350 repeats) was expanded in somatic cells of the progeny in all
      patients examined. Our results provide evidence of an early postzygotic
      instability of the [AGC] repeat in DM.

PMID- 7561968
TI  - Intrathecal production of specific IgA antibodies in CNS infections.
AB  - Cerebrospinal fluid (CSF) and serum from subjects with herpes simplex
      encephalitis, herpes zoster, mumps meningitis and neuroborreliosis were analysed
      for the presence of immunoglobulin A (IgA) and G (IgG) antibodies to the
      corresponding four antigens. Specific intrathecal IgA antibody synthesis as
      manifested by an elevated index was a frequent finding. Higher IgA index values
      than the corresponding IgG was seen in one third of the samples from subjects
      with herpes simplex encephalitis and herpes zoster. Correlation between specific
      IgG and IgA index was most pronounced for varicella-zoster virus (r = 0.66, P <
      0.001). In subjects with mumps meningitis a strong intrathecal IgA and IgG
      antibody response to Borrelia burgdorferi was demonstrated. Specific herpes
      simplex and varicella-zoster virus IgA was not found to contain secretory
      component, thus contradicting an active secretion into the CNS compartment. In
      conclusion, our data indicate that specific IgA is intrathecally produced in
      herpes simplex encephalitis, herpes zoster and mumps meningitis but is a rare
      finding in neuroborreliosis.

PMID- 7561969
TI  - Becker muscular dystrophy presenting with complete heart block in the sixth
      decade.
AB  - Becker muscular dystrophy may be associated with myocardial abnormalities which
      are usually diagnosed after the onset of weakness. We present a patient who
      developed complete heart block 6 years before the onset of muscle weakness which
      occurred unusually late at the age of 62 years.

PMID- 7561970
TI  - Diagnosing Alzheimer's disease in elderly, mildly demented patients: the impact
      of routine single photon emission computed tomography.
AB  - Based on the observation of bilateral temporoparietal hypoperfusion in
      Alzheimer's disease (AD), single photon emission computed tomography (SPECT) is
      advocated by some as a powerful diagnostic tool in the evaluation of demented
      patients. We studied whether routine brain SPECT in elderly, mildly demented
      outpatients increases the a priori diagnostic sensitivity and specificity of a
      careful clinical examination. 99mTc-HMPAO SPECT imaging was performed in 110
      patients for a first evaluation for dementia. A semiquantitative measure of
      temporoparietal (TP) perfusion was calculated as the ratio of the activity in the
      temporoparietal cortex to activity in the cerebellum. A diagnosis of probable AD
      according to the McKhann criteria was made in 68 patients (mean age of 79.3
      years) based on the results of a clinical examination, ancillary investigations
      and a 6-month follow-up. TP perfusion was significantly lower in AD patients than
      in 18 age-matched, non-demented controls. However, at a specificity of 89%,
      sensitivity was only 43% for detecting probable AD. The clinicians judged that
      SPECT had contributed to the final diagnosis in only 8% of the demented patients
      investigated. Routine brain SPECT in elderly, mildly demented outpatients does
      not contribute substantially to diagnostic accuracy after a careful clinical
      examination using current diagnostic criteria. Clinical guidelines have to be
      developed for the use of SPECT in patients with (suspected) dementia.

PMID- 7561972
TI  - Neuroacanthocytosis presenting with epilepsy.

PMID- 7561971
TI  - Neurophysiological assessment of peripheral nerve and spinal cord function in
      asymptomatic HIV-1 infection: results from the UCMSM/Medical Research Council
      neurology cohort.
AB  - As part of the Medical Research Council prospective study of the neurological
      complications of HIV infection, neurophysiological tests of spinal cord and
      peripheral nerve function were recorded in a cohort of homosexual or bisexual
      men. The studies included motor and sensory nerve conduction studies, vibration
      perception thresholds, somatosensory evoked potentials and motor evoked
      potentials elicited by magnetic stimulation. The results were compared with
      markers of immune function. The findings from 114 volunteers were analysed in a
      cross-sectional study. Fifty-nine were HIV-seropositive but asymptomatic, 26 had
      progressed to the symptomatic stages of HIV disease and 29 were persistently HIV
      seronegative. There was some evidence of a mild sensory axonopathy in the
      symptomatic HIV-seropositive group. No differences were detected between the
      asymptomatic HIV-seropositive group and the HIV-seronegative comparison group.
      There were no consistently significant correlations between the
      neurophysiological measurements and CD4 counts and beta 2-microglobulin levels.
      On repeated testing, there was no evidence of a trend towards deterioration over
      a mean period of approximately 3 years in 36 HIV-seropositive subjects who
      remained asymptomatic compared with 22 HIV-seronegatives. These findings have
      failed to demonstrate neurophysiological evidence of spinal cord or peripheral
      nerve dysfunction in the asymptomatic stages of HIV infection.

PMID- 7561973
TI  - Replacement of steric 6-12 potential-derived interaction energies by atom-based
      indicator variables in CoMFA leads to models of higher consistency.
AB  - The steric descriptors commonly used in CoMFA--Lennard-Jones 6-12 potential
      derived interaction energies calculated between a probe atom and the molecules
      under investigation--have been replaced by variables indicating the presence of
      an atom of a particular molecule in predefined volume elements (cubes) within the
      region enclosing the ensemble of superimposed molecules. The resulting 'atom
      indicator vectors' were used as steric fields in the subsequent PLS analyses,
      with and without inclusion of electrostatic Coulomb interaction-derived fields.
      Application of this method to five training sets (80 compounds each) and five
      test sets (60 compounds each), randomly selected from an ensemble of 256
      dihydrofolate reductase inhibitors, leads to models of significantly higher
      consistency, as indicated by the cross-validated r2 values for the training sets
      and the predictive r2 values for the test sets.

PMID- 7561974
TI  - PRO_LIGAND: an approach to de novo molecular design. 4. Application to the design
      of peptides.
AB  - In some instances, peptides can play an important role in the discovery of lead
      compounds. This paper describes the peptide design facility of the de novo drug
      design package, PRO_LIGAND. The package provides a unified framework for the
      design of peptides that are similar or complementary to a specified target. The
      approach uses single amino acid residues, selected from preconstructed libraries
      of different residues and conformations, and places them on top of predefined
      target interaction sites. This approach is a well-tested methodology for the
      design of organics but has not been used for peptides before. Peptides represent
      a difficulty because of their great conformational flexibility and a study of the
      advantages and disadvantages of this simple approach is an important step in the
      development of design tools. After a description of our general approach, a more
      detailed discussion of its adaptation to peptides is given. The method is then
      applied to the design of peptide-based inhibitors to HIV-1 protease and the
      design of structural mimics of the surface region of lysozyme. The results are
      encouraging and point the way towards further development of interaction site
      based approaches for peptide design.

PMID- 7561975
TI  - Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A
      chain active site.
AB  - Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a
      conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis.
      Molecular-dynamics simulation methods are used to analyze the structural
      interactions and thermodynamics that govern the binding of formycin 5'
      monophosphate (FMP) and several of its analogs to the active site of ricin A
      chain. Simulations are carried out initiated from the X-ray crystal structure of
      the ricin-FMP complex with the ligand modeled as a dianion, monoanion and
      zwitterion. Relative changes in binding free energies are estimated for FMP
      analogs constructed from amino substitutions at the 2- and 2'-positions, and from
      hydroxyl substitution at the 2'-position.

PMID- 7561976
TI  - Flexible matching of test ligands to a 3D pharmacophore using a molecular
      superposition force field: comparison of predicted and experimental conformations
      of inhibitors of three enzymes.
AB  - A computer procedure TFIT, which uses a molecular superposition force field to
      flexibly match test compounds to a 3D pharmacophore, was evaluated to find out
      whether it could reliably predict the bioactive conformations of flexible
      ligands. The program superposition force field optimizes the overlap of those
      atoms of the test ligand and template that are of similar chemical type, by
      applying an attractive force between atoms of the test ligand and template which
      are close together and of similar type (hydrogen bonding, charge,
      hydrophobicity). A procedure involving Monte Carlo torsion perturbations,
      followed by torsional energy minimization, is used to find conformations of the
      test ligand which cominimize the internal energy of the ligand and the
      superposition energy of ligand and template. The procedure was tested by applying
      it to a series of flexible ligands for which the bioactive conformation was known
      experimentally. The 15 molecules tested were inhibitors of thermolysin, HIV-1
      protease or endothiapepsin for which X-ray structures of the bioactive
      conformation were available. For each enzyme, one of the molecules served as a
      template and the others, after being conformationally randomized, were fitted.
      The fitted conformation was then compared to the known binding geometry. The
      matching procedure was successful in predicting the bioactive conformations of
      many of the structures tested. Significant deviation from experimental results
      was found only for parts of molecules where it was readily apparent that the
      template did not contain sufficient information to accurately determine the
      bioactive conformation.

PMID- 7561977
TI  - MAB, a generally applicable molecular force field for structure modelling in
      medicinal chemistry.
AB  - The mathematical formulation, parametrization scheme, and structural results of a
      new, generally applicable molecular force field are presented. The central
      features are a scheme for automatic parameter assignments, the consistent united
      atom approximation, the absence of atom types other than elements, the
      replacement of electrostatic terms by geometrical hydrogen-bonding terms, the
      concomitant lack of a need for partial atomic charge assignment and the strict
      adherence to a finite-range design. As a consequence of omitting all hydrogen
      atoms, optimal hydrogen-bond patterns are computed dynamically by appropriate
      network analyses. For a test set of 1589 structures, selected from the Cambridge
      Structural Database solely on the grounds of a given element list and criteria
      for high structure refinement, the agreements are on average 2 pm for bonds, 2
      degrees for valence angles and 10 to 20 pm for the root-mean-square deviation of
      atom positions, depending somewhat on size and flexibility of the structures.
      More qualitative testing of large-scale structural properties of the force field
      on proteins and DNA oligomers revealed satisfactory performance.

PMID- 7561978
TI  - BUILDER v.2: improving the chemistry of a de novo design strategy.
AB  - Significant improvements have been made to the de novo drug design program
      BUILDER. The BUILDER strategy is to find molecule templates that bind tightly to
      'hot spots' in the target receptor, and then generate bridges to join these
      templates. In this paper, the bridging algorithm has been further developed to
      improve the chemical sense and diversity of the bridges, as well as the
      robustness of the technique. The improved algorithm is then applied to rebuild
      known bridges in methotrexate and HIV protease. Finally, the entire BUILDER
      approach is tested by rebuilding methotrexate de novo.

PMID- 7561979
TI  - Quantitative structure-agonist activity relationship of capsaicin analogues.
AB  - The MULTIple Computer Automated Structure Evaluation (MULTICASE) methodology has
      been used to study the quantitative structure-agonist activity relationship of a
      series of capsaicin agonists. A number of substructures and physiochemical
      properties of capsaicin analogues were identified as being responsible for high
      agonist potency. The optimal log P value for the agonist potency as estimated
      from QSAR analysis is 5.12. It was also found that a cluster of inactive
      molecules in the database have lipophilicity values below 2.94. Molecular
      modeling was employed to elucidate the detailed structural features of the
      pharmacophore of capsaicin analogues. Systematic conformational analysis has
      shown that the activity of capsaicin analogues strongly depends upon their
      ability to reach the required conformational profile. Based upon these
      observations, a three-dimensional pharmacophore model for the capsaicin-receptor
      interactions is proposed.

PMID- 7561980
TI  - The impact of changes in coffee consumption on serum cholesterol.
AB  - To investigate the possible association between changes in coffee consumption and
      serum cholesterol levels, information was obtained from 2109 healthy nonsmokers
      aged 25-65 years at two clinic visits to a preventive medical center between 1987
      and 1991 (mean interval between visits: 16.7 months). After adjusting for age and
      changes in other potential confounders, about 2 mg/dl total cholesterol increase
      was associated with an increase of one cup of regular coffee per day (p < 0.001).
      A dose-response was found among those who decreased regular coffee consumption,
      those who continued the same dose, and those who increased consumption. The same
      trend was observed among those who quit drinking regular coffee, those who never
      drank coffee, and those who started to drink coffee. No change in cholesterol
      level was found among those continuing to consume the same quantity of regular
      coffee compared to those who never drank coffee. The change in cholesterol level
      was not related to consumption of decaffeinated coffee, regular tea,
      decaffeinated tea, or cola with caffeine. To our knowledge, this is the first
      follow-up study correlating change in coffee consumption with change in serum
      cholesterol in a large group of men and women.

PMID- 7561981
TI  - The predictive value of admission heart rate on mortality in patients with acute
      myocardial infarction. SPRINT Study Group. Secondary Prevention Reinfarction
      Israeli Nifedipine Trial.
AB  - The purpose of this study was to assess the predictive value of admission heart
      rate (HR) for in-hospital and 1 year post-discharge mortality in a large cohort
      of patients hospitalized for acute myocardial infarction (MI). Data were derived
      from the SPRINT-2 secondary prevention study population, and included 1044
      patients (aged 50-79), hospitalized in 14 coronary care units in Israel with
      acute MI in the years 1985-1986, before the beginning of thrombolytic therapy in
      acute MI. Demographic, historical and medical data were collected for each
      patient. All deaths during initial hospitalization and 1 year post-discharge were
      recorded. In-hospital mortality was 5.2% for 294 patients with HR < 70 beats/min,
      9.5% for 532 patients with HR 70-89 beats/min, and 15.1% for 323 patients with HR
      > or = 90 beats/min (p < 0.01). One year post-discharge mortality was 4.3% for
      patients with HR < 70 beats/min, 8.7% for patients with HR 70-80 beats/min and
      11.8% for patients with HR > or = 90 beats/min (p < 0.01). An increasing trend of
      mortality with higher HR was confined to patients with mild CHF (p = 0.02) and
      likely to patients with absent CHF (p = 0.06), but this post hoc observation
      requires confirmation in larger groups. The combination of high admission HR (>
      or = 90 beats/min) and a systolic blood pressure < 120 mmHg was a powerful
      predictor of in-hospital mortality. Multivariate analysis showed that admission
      HR was an independent risk factor for in-hospital and 1 year post-discharge
      mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7561982
TI  - The "utility" of the Time Trade-Off method in cancer patients: feasibility and
      proportional Trade-Off.
AB  - We examined the feasibility and the proportional trade-off assumption of the Time
      Trade-Off method. Utilities were assessed of the actual health states of 54
      testicular and 72 colorectal cancer patients, treated with the curative intent
      and 29 incurable colorectal cancer patients. Three periods of time were used to
      assess proportionality: the subject's life expectancy and two shorter periods.
      Results showed the method to be feasible in curatively treated patients, though
      the use of life expectancy posed difficulties in some very old subjects. This
      same difficulty was encountered in patients with symptomatic incurable disease. A
      two step procedure is proposed as a solution. The proportional trade-off
      assumption was violated. Utilities for the longer period were smaller than those
      for the shorter periods. Life expectancy and trade-off did not correlate, though.
      Remarkable was that many patients were unwilling to trade at all. The
      implications of the findings are discussed.

PMID- 7561983
TI  - Measuring patient and relative satisfaction with level or aggressiveness of care
      and involvement in care decisions in the context of life threatening illness.
AB  - The objective of the study was to develop valid and reliable discriminative
      indices which measure patient and relative satisfaction with two closely related
      aspects of medical care: the level of care received and their involvement in
      decisions regarding care. We generated items by literature review and interviews
      with patients, relatives, and health care providers. In the final questionnaires,
      we included the items identified most frequently as sources of dissatisfaction
      and rated most important by 102 patients and 153 relatives. To measure
      reliability and validity we administered the instruments to 105 patients and 75
      relatives of competent patients and 89 relatives of incompetent patients. We
      constructed three questionnaires: the Patient Satisfaction Index with 23 items,
      the Relative of Competent Patient Satisfaction Index with 34 items, and the
      Relative of Incompetent Patient Satisfaction Index with 29 items. We found mean
      scores of 75-80% of the maximum possible score, with a wide range of scores. The
      intraclass correlation for the instruments varied from 0.86 to 0.94. Correlations
      with global ratings were high (0.59-0.75) and similar to predictions.
      Correlations with caregiver ratings were lower than predicted (0.18-0.22). For
      both patients and relatives, our instruments discriminate between those with
      higher and lower satisfaction with the level of medical care and with their
      involvement with decision-making.

PMID- 7561985
TI  - PEAPS-Q: a questionnaire to measure the psychosocial effects of having an
      abnormal pap smear. Psychosocial Effects of Abnormal Pap Smears Questionnaire.
AB  - We have developed the Psychosocial Effects of Abnormal Pap Smears Questionnaire
      (PEAPS-Q) which measures distress experienced by women undergoing follow-up
      investigation after an abnormal Pap smear result. A thorough literature review
      and qualitative research resulted in the development of a questionnaire which was
      tested on 350 women attending a Family Planning New South Wales (FPNSW) clinic.
      This sample included women at different stages of management after detection of a
      cervical abnormality: 93 first colposcopy clients and 257 follow-up colposcopy
      clients. Factor analysis identified four dimensions of distress: experience of
      medical procedures, beliefs/feelings about cervical abnormality and changes in
      perception of oneself, worry about infectivity and effect on sexual
      relationships. Repeatability of the PEAPS-Q was indicated by intra-class
      correlations of 0.88 overall and at least 0.60 for each scale. Internal
      consistency was shown by Cronbach's alpha of 0.84 overall and at least 0.72 for
      each scale. Validity was demonstrated by the correlation of scale scores with the
      12-item General Health Questionnaire (GHQ) score of 0.32 (95% CI 0.22-0.41). The
      PEAPS-Q is a valid, reliable and multidimensional instrument for quantifying
      distress experienced by women with abnormal Pap smears.

PMID- 7561984
TI  - Are self-reports of smoking rate biased? Evidence from the Second National Health
      and Nutrition Examination Survey.
AB  - This study determined evidence for digit preference in self-reports of smoking in
      the Second National Health and Nutrition Examination Survey (NHANES II). Subjects
      were 4275 adult smokers. Self-reports of smoking showed a marked degree of digit
      preference, with the vast majority of smokers reporting in multiples of 10
      cigarettes per day. When number per day was compared to an objective measure of
      smoking exposure (carboxyhemoglobin; n = 2070) the distribution was found to be
      significantly assymetrical. Analysis of the distribution of COHb and various
      levels of number per day indicates that the differences in distribution are not
      due to variability in COHb. Heavier smokers, Caucasians, and those with less
      education were more likely to report a digit preference than lighter smokers.
      African-Americans, and those with more education. Results suggest that self
      reports of number of cigarettes per day may be biased towards round numbers
      (particularly 20 cigarettes per day). Implications for assessment of smoking
      behavior are discussed.

PMID- 7561986
TI  - Latex particle agglutination test in the diagnosis of Haemophilus influenzae type
      B, Streptococcus pneumoniae and Neisseria meningitidis A and C meningitis in
      infants and children.
AB  - The knowledge of purulent meningitis etiology is essential in deciding the
      immediate therapy; in developing countries, however, the etiological agent
      identification does not reach 60% of the cases. A comparative study using the
      latex particle agglutination test (LPAT) in cerebrospinal fluid (CSF) for the
      diagnosis of meningitis due to Haemophilus influenzae type b, Streptococcus
      pneumoniae or Neisseria meningitidis A and C was carried out in Belo Horizonte
      MG, Brazil. CSF culture was used as a gold-standard. Two hundred and ninety-nine
      children, ranging from 3 months to 14 years of age, were included in the
      investigation. One hundred and forty-four presented a positive CSF culture for
      the above mentioned bacteria; the remaining presented meningitis due to other
      organisms (other bacteria or viral) or a normal CSF. The sensitivity and the
      specificity of LPAT was 95.7 and 100.0% for N. meningitidis C, 95.2 and 100.0%
      for H. influenzae type b and 86.5 and 100.0% for S. pneumoniae, respectively.
      When all three organisms were considered simultaneously, the sensitivity and the
      specificity was 93.0 and 100.0%, respectively. Taking into consideration a
      realistic estimate of disease prevalence in the community where the diagnostic
      test is being used, the positive predictive value and the posttest probability
      were estimated as 36.7 and 47.1% for children < 5 years and as 21.3 and 35.1% for
      children < 14 years of age, respectively. LPAT is a useful diagnostic test for
      meningitis due to the studied pathogens, especially in developing countries where
      laboratory facilities are limited.

PMID- 7561987
TI  - The accuracy of environmental tobacco smoke exposure measures among asthmatic
      children.
AB  - This study determined the reliability and validity of parent-reported measures of
      environmental tobacco smoke (ETS) exposure among 91 asthmatic children. Test
      retest reliability assessments were conducted for environmental, biological and
      parent-reported measures of ETS exposure. All measures except a urine cotinine
      assay resulted in satisfactory levels of reliability. The parent-reported
      measures of ETS exposure were compared to the environmental filter measure of
      nicotine as well as submitted to a construct validity test. Parent-reported home
      exposure to ETS proved moderately and significantly correlated to the filter
      measure. Approximately 80% of all hypothetical constructs agreed with the
      observed relationships for convergent, divergent and discriminant validity. It
      was concluded that middle class Caucasian parents' reports of their asthmatic
      child's residential ETS exposure are reliable and valid. These parent-reported
      measures should be valuable tools for epidemiological investigations and for
      clinical programs designed to reduce asthmatic children's residential exposure to
      ETS.

PMID- 7561988
TI  - Reduced fertility after the crash of a U.S. bomber carrying nuclear weapons? A
      register-based study on male fertility.
AB  - A register-based study was performed to elucidate whether workers employed on the
      Thule air base in the clean-up period after the crash of a U.S. B-52 bomber
      carrying nuclear bombs had reduced fertility, as measured by the numbers of
      liveborn children. The highest birth rates were among 25-34-year olds with 1-3
      years of employment on the base, but who had not worked at the base the year
      before, who already had one child, with a 2-5-year interval since the birth of
      the last child. No difference was seen between the group of men who had worked at
      the base during the clean-up period after the crash--the possibly exposed group-
      and those people who had worked at the base only outside the clean-up period.
      Because of the massive media coverage and possible claims for damages a register
      based study is the only practicable way of elucidating statements about
      infertility. The main conclusion is that the accident has not reduced fertility.

PMID- 7561989
TI  - Aspirin, salicylate, sulfite and tartrazine induced bronchoconstriction. Safe
      doses and case definition in epidemiological studies.
AB  - Allergic-like reactions to chemical components of foods and medicines may be
      common. The prevalence of idiosyncratic reactions to aspirin, salicylate,
      metabisulfite and tartrazine is not known. We used a tertiary referral clinic
      population to estimate safe exposure doses for epidemiological studies. A 15%
      decrease in the amount of air expired in one second was defined a positive
      response. The median effective molar doses of the agents were remarkably similar:
      metabisulfite 0.19 mM, 34.4 mg [95% confidence interval (CI) 0.14, 0.27 mM];
      tartrazine 0.10 M, 55.0 mg (95% CI 0.05, 0.21 mM); aspirin 0.09 mM, 16.5 mg (95%
      CI 0.04, 0.19 mM); and salicylate 0.11 mM, 15.3 mg (95% CI 0.05, 0.27 mM). Doses
      to which the most sensitive (5%) and practically all (95%) susceptible persons
      might respectively respond are: metabisulfite 4.6 mg, 255.8 mg; tartrazine 3.4
      mg, 885.6 mg; aspirin 0.8 mg, 332.3 mg; and salicylate 2.6 mg, 89.9 mg. Doses
      within these ranges can be used in epidemiological studies.

PMID- 7561990
TI  - Increased asthma hospitalizations among registered Indian children and adults in
      Saskatchewan, 1970-1989.
AB  - We investigated asthma morbidity in children and adults among Registered Indians
      in Saskatchewan using hospitalization data for 1970-1989. In Registered Indians,
      significant increases were observed in the asthma hospitalization rates from 1979
      to 1989 in boys and girls under 4 years, boys aged 5-14 years, and female adults
      aged 15-34 years respectively. In children under 4 years, the asthma
      hospitalization rates increased from 12.7 per 1000 in 1979 to 21.7 per 1000 in
      1989. Asthma hospitalizations were higher among Indian boys than girls in the age
      group 0-4 years but this was reversed in the age groups 15-34 and 35-64 years.
      When compared with other Saskatchewan populations, the Indian population in age
      groups 0-4 and 35-64 years had significantly increased risk for hospitalization
      for asthma. Even though asthma was reported to be rare among Indians before 1975,
      we observed increases in asthma morbidity in recent years among Indian children
      and young adults.

PMID- 7561991
TI  - Rural elders and the decision to stop driving.
AB  - The purpose of this study was to describe the factors involved in rural older
      adults' decisions to stop driving. The sample was 30 men and 45 women with a mean
      age of 83.6 years. Prior accidents, feelings of insecurity about driving,
      impaired health, and the influence of family and friends were found to be
      significant factors in the decision to forfeit a driver's license. Regret and a
      sense of isolation were consequences of that decision.

PMID- 7561992
TI  - A professional challenge: nurses and smoking.

PMID- 7561993
TI  - Community health nurses' HIV care behavior.
AB  - The purpose of this study was to examine community health nurses' attitudes,
      subjective norms, and intentions to care for patients who are HIV positive using
      the theory of reasoned action. One hundred and forty-five participants completed
      a questionnaire developed according to guidelines described by Ajzen and Fishbein
      (1980). Consistent with the theory, nurses' attitudes and subjective norms were
      found to be significant predictors of intentions to care for persons who are HIV
      positive (R2 = .15). Personal beliefs found to discriminate between intenders and
      nonintenders were those related to possible consequences for self, family, and
      friends, but not to job-related consequences. In addition, qualitative data
      showed persistent concerns about occupational risk for contracting AIDS. Based on
      the results of this research, it is recommended that nurse educators in both
      clinical and academic settings target specific educational and training
      interventions to include transmission, prevention, and exploration of feelings,
      attitudes, beliefs, and behavioral intentions about HIV-related topics. Further
      theory-based research and testing of interventions to change community health
      nurses' attitudes and beliefs about HIV disease are advocated.

PMID- 7561994
TI  - Prostate cancer in African American men: increasing knowledge and self-efficacy.
AB  - An educational and screening program for prostate cancer designed to increase
      knowledge and self-efficacy in African American men was provided in African
      American churches in a major midwestern city. Modeling was provided by trained
      lay educators who were African American men previously diagnosed and treated for
      prostate cancer and who could serve as role models of the desired behaviors.
      Pretests and posttests developed for this study and provided to the participants
      were the Prostate Cancer Screening Knowledge Inventory and the Prostate Cancer
      Screening Self-Efficacy Scale. Paired t tests demonstrated that after completing
      the church-based intervention, participants had significantly improved knowledge
      and self-efficacy scores related to prostate cancer screening.

PMID- 7561995
TI  - Health care diaries of young women.
AB  - The purpose of this study was to describe young women's self-care activities
      related to health maintenance and symptom management. Seventy-six young adult
      women kept a daily health diary for 3 weeks. They reported a total of 1,213
      health maintenance practices. The self-care interventions used to manage symptoms
      were varied and specific to the reported symptoms. The most frequently reported
      illness management activity was the use of over-the-counter medications. The self
      care measures selected by these young women reflect deliberate approaches to
      their situations. The findings suggest that nurses in the community should use
      young adult health promoting and health maintaining behaviors as a basis for
      designing interventions.

PMID- 7561996
TI  - Transbronchial regional electroplethysmography of the lungs.
AB  - OBJECTIVE: The objective of this study was to describe a method of transbronchial
      regional electroplethysmography of the lungs. METHODS: The electrical resistance
      of a division of a lung, such as a segment or subsegment, as well as its
      pulsatile oscillation, were measured using a two-part process: A catheter
      transducer was wedged into a small bronchus and the electrical resistance of a
      blood sample obtained from the same patient was measured. The
      electroplethysmograph (EPG) was developed for this purpose. The theory behind our
      method is based on a model of the lung as a three-component structure (blood
      tissue-air). We performed experiments on isolated lung lobes of animals, using
      simultaneous electrometric and direct determination of physiologic indices for
      regional lung function. RESULTS: Equations have been proposed to calculate blood
      volume, Vb (+/- 10%); air volume, Va (+/- 11%); pulsatile increment of the blood
      volume, delta V (+/- 10%); and regional stroke volume, RSV (+/- 20%) per 100 cm3
      of the lung. The proposed formulas yield an accuracy that is adequate for the
      clinical range of variations in Vb and Va, as well as delta V and RSV.
      Experiments on lung lobes indicate that the conductivity of lung tissue (gamma t)
      is not large. This allows one to calculate the above indices without our having
      obtained accurate values for conductivity. CONCLUSIONS: The method of
      Transbronchial regional electroplethysmography of the lungs is described and
      cases in which this method was used for clinical investigation are presented.

PMID- 7561997
TI  - Reflectance pulse oximetry at the forehead improves by pressure on the probe.
AB  - In this study, we investigated the possibility of improving reflectance (back
      scatter) pulse oximetry measurements by pressure applied to the probe. Optimal
      signal detection, with the probe applied to an easily accessible location, is
      important to prevent erroneous oxygen saturation readouts. At the foreheads of 10
      healthy adult volunteers, the effects of pressure applied onto the reflectance
      pulse oximeter probe were studied. Distances between the LEDs (660 nm and 940 nm)
      and the three photodiodes in the sensor were 4 mm, 7 mm, and 10 mm. For each
      detector, recordings were evaluated regarding red-to-infrared (R/IR) ratios and
      pulse sizes in relation to the stepwise increased pressure applied to the probe.
      R/IR variability decreased with applied pressures between 60 and 120 mm Hg. These
      findings are partly attributed to a corresponding increase in red and infrared
      pulse sizes at the detectors, which results in an improved signal-to-noise ratio.
      It is thought that pressure onto the oximeter sensor forces venous blood out of
      the tissues underneath the sensor. Consequently, the disturbing influence of
      pulsating and non-pulsating venous blood is reduced. Moreover, the increased
      difference in vessel diameter between diastole and systole and the corresponding
      difference in light absorption and an increase in flow velocities, causes an
      increase in pulse size with increasing pressure on the probe. Pressure applied to
      the probe may be useful in increasing the accuracy of reflectance pulse oximetry.

PMID- 7561998
TI  - Clinical evaluation of continuous noninvasive blood pressure monitoring: accuracy
      and tracking capabilities.
AB  - A continuous, noninvasive device for blood pressure measurement using pulse
      transit time has been recently introduced. We compared blood pressure measurement
      determined using this device with simultaneous invasive blood pressure
      measurements in 35 patients undergoing general endotracheal anesthesia. Data were
      analyzed for accuracy and tracking ability of the noninvasive technique, and for
      frequency of unavailable pressure measurements by each method. A total of 25,133
      measurements of systolic pressure, diastolic pressure, and mean arterial pressure
      (MAP) by each method were collected for comparison from 35 patients. Accuracy was
      expressed by reporting mean bias (invasive pressure minus noninvasive pressure)
      and limits of agreement between the two measurements. After correction for the
      offset found when measuring invasive and oscillometric methods of arterial
      pressure measurement, the mean biases for systolic, diastolic, and mean pressures
      by the pulse wave method were -0.37 mm Hg, -0.01 mm Hg, and -0.05 mm Hg,
      respectively (p < 0.001). The limits of agreement were: -29.0 to 28.2 mm Hg, 
      14.9 to 14.8 mm Hg, and -19.1 to 19.0 mm Hg, respectively (95% confidence
      intervals). When blood pressure measured invasively changed over time by more
      than 10 mm Hg, the noninvasive technique accurately tracked the direction of
      change 67% of the time. During the entire study, 3.2% of the invasive
      measurements were unavailable and 12.9% of the noninvasive measurements were
      unavailable. The continuous noninvasive monitoring technique is not of sufficient
      accuracy to replace direct invasive measurement of arterial blood pressure, owing
      to relatively wide limits of agreement between the two methods.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7561999
TI  - Limitations of forehead pulse oximetry.
AB  - During initial clinical tests to calibrate our reflectance pulse oximetry system,
      we observed serious physiologic limitations to the use of pulse oximetry in the
      forehead region. We present a case of simultaneous reflectance and transmission
      mode pulse oximetry monitoring in a child undergoing cardiac surgery for
      congenital cyanotic heart disease with a large intracardiac shunt. During general
      anesthesia, when the patient was endotracheally intubated and mechanically
      ventilated, the transmission mode saturation agreed well with arterial oxygen
      saturation measurements; but, our reflectance pulse oximeter, with the sensor
      applied to the forehead, displayed spuriously lower (-18%) oxygen saturations.
      Before and after anesthesia and surgery, there was fine agreement between
      reflectance and transmission mode saturation values. We suggest that the
      difference was caused by vasodilatation and pooling of venous blood due to
      compromised venous return to the heart, and a combination of arterial and venous
      pulsations in the forehead region. This means that the reflectance pulse oximeter
      measured a mixed arterial-venous oxygen saturation.

PMID- 7562000
TI  - Validation of blood pressure measuring devices.

PMID- 7562001
TI  - Tissue distribution of methotrexate following administration as a solution and as
      a magnetic microsphere conjugate in rats bearing brain tumors.
AB  - A novel magnetic microsphere-methotrexate (MM-MTX) drug delivery system was
      synthesized and evaluated in rats bearing rat glioma-2 (RG-2) tumors.
      Methotrexate was linked to the surface of the magnetic particle via an
      aminohexanol linker that would release free drug following hydrolysis. Male
      Fischer 344 rats bearing RG-2 tumors were administered 3 mg/kg of methotrexate
      (MTX) either as MM-MTX or as a solution (MTX-S) over 5 min. A 6000 gauss magnetic
      field was applied for 15 min from the end of MM-MTX administrations. Serial
      sacrifices were conducted at 15 min, 30 min and 45 min after drug
      administrations, organs collected, and analyzed for total MTX by a radioassay. At
      all times, MTX right brain (ipsilateral), brain tumor, and left brain
      concentrations were approximately 3.5 to 5-fold greater in the MM-MTX group
      compared to the MTX-S group. MTX concentrations in all other organs were less
      following administration of MM-MTX than MTX-S except in lung at 30 and 45 min.
      The targeting efficacy, an index for site-specificity, for both MM-MTX and MTX-S
      were similar and indicated some enhancement in MTX localization in brain tumor.
      Confocal and conventional light microscopic analyses demonstrated a diffuse
      distribution of MM-MTX in tumor consistent with extravascular uptake, whereas a
      predominant capillary distribution of MM-MTX was observed in normal brain.
      Following 45 min, the animals treated with MM-MTX died possibly due to
      redistribution of particles to the lung. This toxicity was dose-dependent. High
      brain MTX concentrations coupled with extravascular uptake of MM-MTX provide a
      basis for further investigations with this novel drug delivery system.

PMID- 7562002
TI  - Metabolic patterns in malignant gliomas.
AB  - Changes of mitochondrial and cytoplasm tumor metabolism were studied in malignant
      gliomas and normal cortex probes in vitro. By spectrophotometric methods marker
      enzymes of different mitochondrial (whole respiratory chain, citrate acid cycle,
      fatty oxidation) and cytoplasm (glycolysis, pentose phosphate shunt) metabolic
      energy pathways were analysed. Generally, the activities of intramitochondrial
      key enzymes were significantly decreased in gliomas when compared with enzyme
      activities of normal cortex tissue (p < 0.01). Glycolytic enzymes and a
      representative of the pentose phosphate shunt were unchanged or increased. Ratios
      of marker enzymes of the glycolytic pathway (lactate dehydrogenase) and glycose-6
      P dehydrogenase revealed a significant difference between glioblastomas (p <
      0.05) and grade III (p < 0.05) tumors in comparison to normal astrocytic tissue
      and astrocytomas WHO grade II. Thus, biochemical analyses allow metabolic grading
      of gliomas in vitro and may be a useful tool for understanding tumor biology.

PMID- 7562003
TI  - Analysis of proliferative grade in glial neoplasms using antibodies to the Ki-67
      defined antigen and PCNA in formalin fixed, deparaffinized tissues.
AB  - In an effort to optimize immunocytochemical methods to evaluate cell kinetics in
      brain tumors, we studied two newly-developed antibodies which react with formalin
      resistant epitopes of Proliferating Cellular Nuclear Antigen (PCNA) and Ki-67.
      These results were compared with standard flow cytometric cell cycle data from
      the same tumor specimens to determine if these methods correlate with each other,
      and whether retrospective analysis using these antibodies is feasible for cell
      kinetic analysis of brain tumors. Thirty-one specimens of glial tumors submitted
      for flow cytometry during 1992 were also reacted with antibodies to PCNA (PC-10)
      and Ki-67 (MIB-1). Flow cytometry scores for S-phase Fraction were compared with
      immunocytochemical scores for both antibodies, using an arbitrary rating of 1
      (low, < 4%), 2 (intermediate, 4-6%), 3 (high, > 6%), and 1 (< 25% positive), 2
      (26-75% positive), 3 (> 75% positive), respectively. MIB-1 results were found to
      correlate significantly with the S-phase fraction as determined by flow
      cytometry. The MIB-1 data showed a trend toward underestimating, i.e., lower
      scores, the proliferative index compared with flow cytometry. There was less of a
      correlation between PC-10 antibody scores and flow cytometry S-phase fraction, as
      PC-10 immunostaining typically overestimated the proliferative rate of brain
      tumors when compared with flow cytometry. There was an exact correlation between
      PC-10 and MIB-1 in only 4 cases, whereas in the remaining specimens, PC-10
      results were always higher than MIB-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562004
TI  - Growth inhibition of rat glioma cells in vitro and in vivo by aspirin.
AB  - The effect of non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic
      acid (commonly known as aspirin), salicylic acid, piroxicam and indomethacin on
      the growth of rat glioma cells (RG 2) in vitro and aspirin in vivo was studied.
      The in vitro studies reveal that aspirin and salicylic acid strongly inhibit
      growth of rat glioma (RG 2) cells in concentrations used in medicine for
      treatment of rheumatic diseases. On the other hand, indomethacin and piroxicam
      had no effect, indicating that the inhibitory effect on tumor growth is not due
      to the inhibition of prostaglandin synthesis. The synthesis of ATP was markedly
      reduced (34% of control) in the presence of drugs, whereas protein synthesis
      measured as 3H-leucine incorporation was slightly more inhibited (73% of control)
      than cell growth. Aspirin administered to Fischer 344 rats inhibited growth of RG
      2 cells inoculated into the caudate nucleus in vivo, both when administered the
      day before inoculation of tumor cells and when tumors had formed, i.e. 5 days
      post inoculation.

PMID- 7562005
TI  - Cell adhesion molecules acting between C6 glioma and endothelial cells.
AB  - The interactions between tumor cells and endothelium play a key role in the
      process of tumor growth, local invasion, and distant metastasis. In the present
      study, we examined the adhesion of C6 glioma cells to bovine endothelial cell
      (EC) monolayers and defined the cell adhesion molecules acting between these
      cells. Pretreatment of the EC monolayer with cytokines, tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1 beta, and interferon (INF)-gamma, significantly
      increased the adhesion of C6 glioma cells to the EC monolayer. The effect lasted
      more than 24 hours and was protein-synthesis dependent. The adhesion of C6 glioma
      cells to TNF-activated ECs was blocked by the monoclonal antibody to the
      intercellular adhesion molecule-1 (ICAM-1) or beta 2 integrin, whereas that of
      melanoma cells was not. These findings provide evidence that ICAM-1 and beta 2
      integrin function as inducible cell surface molecules that can support the
      adhesion of C6 glioma cells to ECs, and may contribute to the characteristic
      growth of glial tumors in vivo.

PMID- 7562006
TI  - Intraarterial cisplatin plus intravenous doxorubicin for inoperable recurrent
      meningiomas.
AB  - The majority of meningiomas are cured by surgical resection. There is little
      information in the literature on the use of chemotherapy in meningiomas. We
      report 2 patients with inoperable recurrences of meningiomas that responded (1
      patient) or stabilized (1 patient) when treated with the combination of
      intracarotid cisplatin plus intravenous doxorubicin.

PMID- 7562008
TI  - Loss of porins following carbapenem-resistance selection and adherence
      modification in enterobacteria.
AB  - The acquired resistance to the carbapenems is frequently joined to modified
      expression of porins or other outer membrane (OM) structures, thus bacterial
      adherence, that also depends on the presence of peculiar surface structures,
      might theoretically be influenced. In this study the ability to adhere to Hep-2
      and I-407 eukaryotic cell monolayers was assayed for two susceptible strains of
      Serratia marcescens, one strain of Enterobacter cloacae and one of Providencia
      rettgeri in comparison with that of isogenic resistant mutants selected either by
      carbapenems or by cephalosporins. The mutants appeared slightly less adherent
      than the wild type strains, however, due to the high variability of this kind of
      assay, the differences observed in most cases could not be considered
      statistically significant. The data suggest that adherence, among the factors
      affecting the pathogenicity of the strains, remains probably unmodified in the
      resistant bacterial population possibly selected by a carbapenem treatment.

PMID- 7562011
TI  - Erythromycin is ineffective against Listeria monocytogenes in multidrug resistant
      cells.
AB  - Multidrug resistance of tumor cells is a well-known phenomenon in oncology. Among
      the substances excluded from the cells are not only antineoplastic drugs but also
      certain antibiotics, e.g. erythromycin. To prove the hypothesis that this might
      render infections with intracellular bacteria untreatable with these antibiotics
      we used erythromycin to treat intracellular infection of multidrug resistant
      (MDR) cells with Listeria monocytogenes. Erythromycin was unable to restrict the
      growth of L. monocytogenes in KBV-1 MDR cells in concentrations of up to 25
      micrograms/ml. In contrast, 0.049 micrograms/ml of erythromycin were sufficient
      to restrict the growth of the bacteria in nonresistant KB 3-1 cells. When
      verapamil was added to the supernatant of KBV-1 cells, erythromycin regained its
      effectivity on L. monocytogenes multiplying in these cells. The fact that MDR
      cells may render intracellular bacteria inaccessible to certain antibiotics might
      have important implications for the persistence of these bacteria in the host and
      for the treatment of patients with genetically engineered MDR cells.

PMID- 7562007
TI  - Epstein-Barr virus and brain lymphomas.

PMID- 7562010
TI  - Comparative in vitro killing activity of meropenem versus imipenem against
      multiresistant nosocomial Pseudomonas aeruginosa.
AB  - In order to compare the in vitro killing activity of meropenem and imipenem
      against multiresistant P.aeruginosa 14 strains were used. All nosocomial isolates
      were susceptible to meropenem and imipenem minimum inhibitory concentration (MIC
      < or = 4 micrograms/ml) and resistant to at least two other antimicrobial agents
      of diverse chemical class with antipseudomonal activity. Forty-two killing curves
      were performed by exposing a 5 x 10(5) CFU/ml log-phase inoculum to 1x minimum
      bactericidal concentration (MBC) of each carbapenem. Meropenem was found to
      possess a slower killing rate than imipenem over the first 5 hours of
      P.aeruginosa exposure, but to be equally effective as imipenem after 24 hours of
      incubation. Forty percent and 11.1% of P.aeruginosa strains developed resistance
      to imipenem and meropenem respectively after a 24-hour exposure to carbapenem.
      The authors speculate about the underlying mechanisms explaining the higher rate
      of resistance development to imipenem than to meropenem.

PMID- 7562009
TI  - Extended-spectrum beta-lactamases conferring resistance to monobactams and
      oxyimino-cephalosporins in clinical isolates of Serratia marcescens.
AB  - We studied antibiotic resistance patterns and extended-spectrum beta-lactamases
      (ES beta Ls) production in Serratia marcescens strains isolated in our hospital
      during 1993. We examined 210 S. marcescens isolates. Of these, 172 were obtained
      from 49 patients admitted to an intensive care ward; 157 out of 172 were obtained
      from February to October and presented the same pattern of antibiotic resistance,
      including monobactams and oxyimino-cephalosporins. The remaining 15 out of 172
      isolates (obtained from September to December) were susceptible to all drugs
      tested, with the exception of first generation cephalosporins. Thirty-eight
      additional isolates were recovered, during the same period, from 28 patients
      admitted to wards other than the intensive care unit; also these strains showed
      the high susceptibility pattern reported above. Epidemic strains of S. marcescens
      produced three different types of beta-lactamase with pI 5.4, 5.5, and 8.4. In
      contrast, non-epidemic strains produced only one type of beta-lactamase with pI
      8.4. Conjugation experiments showed that the beta-lactamases having a pI of 5.4
      and 5.5 (but not the one with pI 8.4) were plasmid-mediated. Since the beta
      lactamase with pI 5.5 was capable of hydrolyzing monobactams and oxyimino
      cephalosporins it was classified as ES beta L. Electrophoretic analysis showed
      that plasmids obtained from multiresistant strains were of about 54 kb; these
      plasmids appeared also to code for aminoglycoside resistance. Our data indicate
      that the plasmid-mediated production of ES beta Ls may contribute to the epidemic
      spread of Serratia marcescens in high-risk wards.

PMID- 7562012
TI  - In vitro activity of BAY y 3118, and nine other antimicrobial agents against
      anaerobic bacteria.
AB  - The antibacterial activity of BAY y 3118, a new chlorofluoroquinolone, was
      determined against 257 strains of anaerobic bacteria and compared with the
      activities of ofloxacin, ciprofloxacin, sparfloxacin, imipenem, cefoxitin,
      clindamycin, chloramphenicol, metronidazole, and ornidazole. Overall, BAY y 3118
      was the most active agent tested against the Bacteroides fragilis group. Its
      activity (MIC90, 0.5 mg/L) was 16-fold lower than that of sparfloxacin (MIC90, 8
      mg/L), and more than 100-fold lower than that of ofloxacin (MIC90, 64 mg/L) and
      ciprofloxacin (MIC90, 128 mg/L) against the group. No strains belonging to this
      group were resistant to metronidazole (MICs range, 0.12-2 mg/L) and ornidazole
      (MICs range, 0.12-4 mg/L). BAY y 3118 was more active than those quinolones
      against Prevotella and Porphyromonas spp., Fusobacterium spp., Clostridium
      perfringens and C. difficile (MIC90, 0.12, 0.06, 0.12 and 0.25 mg/L,
      respectively). The activity of BAY y 3118 against Peptostreptococcus spp. (MIC90,
      1 mg/L) was slightly lower than that of the other Gram-positive bacteria tested.
      In general, BAY y 3118 was more active than cefoxitin, and it was superior to
      antianaerobic chemical agents like metronidazole, ornidazole and clindamycin.
      Pharmacokinetic and clinical trials are required to define the role of BAY y 3118
      in the treatment of anaerobic infections.

PMID- 7562013
TI  - In vitro activity of levofloxacin and FK-037 against aerobic isolates from
      spontaneous bacterial peritonitis.
AB  - Spontaneous bacterial peritonitis is a potentially fatal complication of ascites,
      most often caused by the Enterobacteriaceae or streptococci. We have evaluated
      the in vitro activity of FK-037, a new cephalosporin, cefotaxime, cefpirome,
      ceftazidime, levofloxacin, and ofloxacin against a collection of 124 isolates
      from patients with spontaneous bacterial peritonitis. Levofloxacin (< or = 2
      mg/L) was active against all isolates and ofloxacin (< or = 2 mg/L) against 98.4%
      of isolates. The cephalosporins (< or = 8 mg/L) were less active against
      cefpirome = 95.4%, FK-037 = 94.4%, and cefotaxime and ceftazidime = 91.1%. Given
      the high mortality associated with spontaneous bacterial peritonitis, clinical
      studies of the quinolones (specifically of levofloxacin) and the alternative
      cephalosporins presented for treatment of spontaneous bacterial peritonitis
      appears warranted.

PMID- 7562014
TI  - In vitro and in vivo antimicrobial action of fluphenazine.
AB  - The antipsychotic drug fluphenazine was obtained in a dry powder form and was
      screened with respect to 482 strains of bacteria, which included 170 Gram
      positive and 326 Gram-negative strains. Nutrient agar plates containing
      increasing concentrations of fluphenazine (0-200 micrograms/ml) were used for the
      determination of the minimum inhibitory concentration (MIC) which was
      demonstrated by inoculating a loopful of an overnight peptone water culture of
      the organism on nutrient agar plates and determining the MIC against a control.
      Fluphenazine was detected to possess pronounced action against both Gram-positive
      and Gram-negative bacteria at 20-100 micrograms/ml. In the in vivo studies it was
      seen that when fluphenazine was used at a concentration of 1.5 micrograms/g and 3
      micrograms/g mouse body weight both the levels offered significant protection to
      Swiss strain of white mice when challenged with 50 minimum lethal dose (MLD) of a
      virulent strain of Salmonella typhimurium 74. The in vivo data with fluphenazine
      were highly significant (p < 0.001) according to the chi-square test.

PMID- 7562016
TI  - Efficacy of herpes vaccine and acyclovir (ACV) in a rabbit model following
      intraocular inoculation of herpes simplex virus.
AB  - It has been shown that injection of herpes simplex virus (HSV) type I into the
      vitreous body of the eye in 18-day-old albino rabbits consistently induced
      encephalitis. In the untreated group the lesions followed a defined anatomical
      pathway in the central nervous system and produced a chronic progressive disease
      with 95% survival. Detailed observations in the spread of HSV along the optic
      pathway determined the extent of damage at any given day. Some of the old rabbits
      developed typical herpetic lesions on nose and lips. HSV was demonstrated from
      these lesions by electron microscopy and also by tissue culture isolation. The
      combined efficacy of heat-killed herpes vaccine prepared from the same isolate
      and acyclovir (ACV) in this animal model was studied by starting treatment four
      days before or four days after the challenge. Ten animals immunised before the
      challenge were protected. However, immunisation after the challenge not only did
      not confer protection, but surprisingly, appeared to enhance the primary disease.
      All 10 rabbits immunised after the challenge developed weakness of the hind legs
      and progressed very rapidly to paralysis. ACV treatment alone did not completely
      abrogate the HSV infection, there appears to be reactivation of HSV which
      produced fresh small lesions. However, a combination of immunisation and
      treatment with ACV after the challenge of the 10 rabbits in the group prevented
      the development of weakness of the hind legs or paralysis. Detailed observations
      on the spread of HSV along the optic pathway revealed that pathological lesions
      and damage were limited in the ACV and combined treatment with ACV and vaccine
      group.

PMID- 7562015
TI  - Methods for determining concentrations of antimicrobial agents in human
      monocytes.
AB  - Human monocytes can be derived from the leukocyte-rich by-product of donors'
      blood available after platelet separation. Large volumes of the monocyte samples
      obtained from this product provided an opportunity to conduct experiments with
      relatively high concentrations of the antimicrobial agents sufficient for their
      detection in bioassays, thus avoiding the necessity of working with the
      radiolabelled drugs. Washing of the cells after their exposure to the drug may
      lead to an extraction of the tested agent from the cell, especially if it is a
      substance of low molecular weight. In our experiments we excluded the washing
      step, and separated the monocytes from the extracellular medium by velocity
      gradient centrifugation. In experiments with two rifamycins, the cell pellet as
      well as the extracellular fluid were subjected to a bioassay using Micrococcus
      luteus as a target organism. The method showed good reproducibility and
      consistency in results obtained.

PMID- 7562017
TI  - Clindamycin/cefonicid in head and neck oncologic surgery: one-day prophylaxis is
      as effective as a three-day schedule.
AB  - The aim of our study was to evaluate the optimal duration of antibiotic
      prophylaxis in major oncologic surgery of the head and neck using a novel broad
      spectrum drug combination: clindamycin and cefonicid. A prospective randomized
      study was carried out on 126 evaluable patients undergoing clean-contaminated
      (skin to mucosa) surgery for cancer of larynx, pharynx or oral cavity. Cases at
      high surgical risk (because of need of pedicled or microvascular free flaps
      reconstruction), were excluded from the study. Within 20 days after surgery, only
      one case of wound infection was recorded among the 62 patients treated with the
      one-day schedule, versus three cases registered among the 64 subjects receiving
      three-day chemoprophylaxis. Episodes of systemic infections and eventual wound
      complications occurring in the first 20 days after surgery have also been
      recorded. The role of potential risk factors for postoperative complications has
      been evaluated. According to our findings, a three-day antibiotic regimen is not
      more effective than a short-term (one-day) schedule in preventing wound or
      systemic infection in clean-contaminated head and neck cancer surgery without
      flap reconstruction.

PMID- 7562018
TI  - Brodimoprim, a new bacterial dihydrofolate reductase inhibitor: a minireview.
AB  - This brief review article synthesizes the principal literature regarding the
      clinical status of co-trimoxazole compared to monotherapy with one of the two
      diaminopyrimidines available commercially: trimethoprim or brodimoprim. Both
      these inhibitors of bacterial dihydrofolate reductase compare favorably to co
      trimoxazole as antimicrobial chemotherapy. Brodimoprim is characterized by its
      advantageous pharmacokinetics in comparison to both co-trimoxazole and
      trimethoprim.

PMID- 7562019
TI  - Cisplatin increases sensitivity of human leukemic blasts to triazene compounds.
AB  - High levels of O6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part,
      account for tumor cell resistance to O6-alkylguanine alkylating agents, including
      triazene compounds. A pilot clinical study indicates that dacarbazine can induce
      a marked decrease of leukemic blasts in patients affected by acute myelogenous
      leukemia (AML) with low pretreatment levels of OGAT activity. In this study we
      show a synergistic antitumor effect between cisplatin (CDDP) and temozolomide (an
      in vitro active analog of dacarbazine), following combined in vitro treatment of
      leukemic blasts. Synergistic effect appears to be CDDP-dose dependent. In vivo
      treatment of leukemic patients with CDDP was followed by a reduction of OGAT
      activity in 2 out 3 cases. These data point out that CDDP could be a good
      candidate for depleting OGAT protein of leukemic cells, thus reversing tumor cell
      resistance to dacarbazine.

PMID- 7562020
TI  - Changing pattern of relapse in osteosarcoma of the extremities treated with
      adjuvant and neoadjuvant chemotherapy.
AB  - In 551 patients with osteosarcoma of the extremities treated between 1980 and
      1991 in our Institution with surgery only (35 cases), surgery combined with
      adjuvant chemotherapy (147 cases) or neoadjuvant chemotherapy (369 cases) the
      relapse patterns were analyzed. Adjuvant chemotherapy was performed according to
      2 different protocols and neoadjuvant chemotherapy according to 3 different
      protocols successively activated. In the 252 patients who relapsed, the interval
      between initial treatment and first relapse was significantly longer in the group
      treated with adjuvant and neoadjuvant chemotherapy (18.1 and 21.3 mo) than in the
      group treated with surgery only (5.4 mo). For patients treated with neoadjuvant
      chemotherapy, a longer interval was seen in the most effective regimen of
      neoadjuvant chemotherapy (25 mo). No significant differences were seen among the
      3 groups, according to the site of first metastasis, although in patients treated
      with the most effective neoadjuvant regimen there was a higher incidence of bone
      metastasis. In patients who relapsed with pulmonary metastases the average number
      of nodules seen by standard X-rays, as well as CT scans, was significantly higher
      in patients treated with surgery only (3.6) than in patients treated with
      adjuvant or neoadjuvant chemotherapy (2.5 and 2.6 nodules). We conclude that
      these changes in metastatic pattern in patients treated with adjuvant and
      neoadjuvant chemotherapy are important, because they may encourage the use of
      salvage therapy with thoracotomy in a larger number of patients. Prolongation of
      time relapsed after more effective regimens of adjuvant and neoadjuvant
      chemotherapy should be considered when evaluating the preliminary results of new
      chemotherapy protocols.

PMID- 7562022
TI  - Oral etoposide as second-line chemotherapy for colorectal cancer: a GISCAD study.
      Gruppo Italiano Studio Carcinomi Apparato Digerente.
AB  - Twenty-one patients with advanced colorectal cancer, all previously pretreated
      with a fluoropyrimidine-based regimen, received oral etoposide: 100 mg/die for 21
      consecutive days, every three weeks. No objective response was achieved; 6 pts
      had a short-lasting stabilization of their disease. Toxicity was substantial and
      mainly represented by myelosuppression and alopecia. Protracted administration of
      etoposide is inactive as second-line treatment of colorectal cancer.

PMID- 7562021
TI  - Is there a role for adjuvant immunochemotherapy after radical nephrectomy in pT2
      3N0M0 renal cell carcinoma?
AB  - Five-year overall survival after radical surgery in N0M0 renal cell carcinoma
      varies from 45-80% in pT2 to 35-50% in pT3 categories. In view of the alpha
      interferon and vinblastine combination which has shown some activity in advanced
      disease with increasing efficacy in limited metastatic invasion, we decided to
      explore the theoretical advantage of adjuvant chemo-immunotherapy in radically
      resected stage II, III renal cell carcinoma. A single-institution phase II study
      was undertaken to evaluate the efficacy and tolerability of alpha 2a-interferon
      (alpha 2a-INF) in combination with vinblastine in 30 patients with pT2-T3 N0M0
      renal cell carcinoma (RCC). Thirty-two patients who received only radical
      nephrectomy and extended lymphadenectomy were analyzed and results were compared
      with the first group. Twenty-three of 30 (76.6%) patients in the first group are
      alive with no evidence of disease. The median follow-up for the 23 patients still
      alive was 67 months (range 60 to 72). Metastases were documented in 5 patients
      (16.6%) with a median interval to progression of 24 months. Four of them (13.6%)
      died of tumor. In the control group, 16 out of 32 patients (50%) are still alive,
      with a median follow-up for the patients still alive of 62 months (range 60 to
      68). Fifteen patients developed distant metastases and 2 of them had a local
      recurrence. All of them (46.8%) died of tumor. Median progression interval was 24
      months. After stratification by pathological grade, site, laterality and number
      of nodes found at lymphadenectomy there were no statistical differences in risk
      of progression or death in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562023
TI  - Undifferentiated nasopharyngeal carcinoma in children: a report of four cases.
AB  - Nasopharyngeal carcinoma in early stages in children is a highly curable
      neoplasm. The major cause of treatment failure is the development of distant
      metastases, predominantly in advanced stages. This paper reports about four young
      patients with undifferentiated nasopharyngeal carcinoma treated with preradiation
      chemotherapy, locoregional radiotherapy and maintenance chemotherapy up to a
      total period of two years. Treating these four children, we noticed that
      preradiation chemotherapy caused satisfactory regression of the primary tumor.
      Three patients are still without signs of disease after 28 to 88 months and one
      died due to tumor progression. Further studies have to confirm our observations
      and support research in designing the optimal combination of effective
      chemotherapeutic agents and radiotherapy.

PMID- 7562024
TI  - Nosocomial Torulopsis glabrata fungemia with shock in a pregnant woman
      successfully treated with high doses of fluconazole and delivery of healthy
      child.

PMID- 7562025
TI  - Instability of short tandem repeats (microsatellites) in human gliomas.
AB  - OBJECTIVE: Microsatellite instability implying multiple replication errors (RER)
      characterizes a proportion of familial and sporadic carcinomas. The purpose of
      this report is to analyze whether microsatellite instability occurred during the
      development of human gliomas. EXPERIMENTAL DESIGN: We checked prospectively 16
      central nervous system tumors, including 10 glioblastomas and 6 astrocytomas of
      different malignancy grades, for genetic microsatellite instability. Fifteen
      different microsatellites, located on 6 different chromosomes, were investigated.
      All microsatellites are dinucleotide CA, repeats except for D11S956,P23 (CTAT)
      and CYP 19, which are tetranucleotide repeats and P23 (GTTTT) which is a
      pentanucleotide repeat. The repeats were analysed by PCR amplification, followed
      by electrophoresis on denaturing 6% polyacrylamide gels. MEASURES: We looked for
      all kinds of microsatellite alterations. Only microsatellite shifts were
      considered to represent microsatellite instability. RESULTS: Three out of 10
      glioblastomas showed mobility shifts on gel electrophoresis in tumor, compared to
      corresponding normal DNA samples. In contrast, no microsatellite instability was
      found in any of the astrocytomas. Besides the presence of larger or smaller
      alleles, an imbalance in the ratio between alleles was noticed in one astrocytoma
      and in one glioblastoma multiforme. In addition, loss of heterozygosity (LOH) is
      observed without a fixed pattern in 3 glioblastomas. CONCLUSIONS: We conclude
      that genetic instability of microsatellites may be demonstrated in high grade
      gliomas rather than in their low grade precursors and should be regarded as an
      evolution in tumor progression rather than as a new mechanism for tumor
      initiation in gliomas.

PMID- 7562026
TI  - Death on neurological grounds.
AB  - During centuries, the loss of spontaneous cardio-pulmonary function was found to
      predict permanent non-functioning of the "organism as a whole", therefore serving
      adequately as a criterion of death, but during the era of Intensive Care, there
      was a shift to brain-oriented definitions of death, ie, the irreversible
      cessation of brain functions, started to be considered as the main reason for
      cessation of functioning of the "organism as a whole". A concept or definition of
      death is related to the question: What is it "about human life, which is
      irreplaceable by any artifice, and that its loss is so essential, that the
      individual who loses it ought to be called dead?" Further work has been centered
      on how much of the brain needs to be dead, before a person can be declared dead
      on neurological grounds: "whole brain", "brainstem death" ("brain as a whole")
      and "higher brain" formulations of death. These brain-oriented formulations of
      death are discussed and criticized, with the conclusion that although there is
      only one function, irreplaceable, which characterizes the human being: the
      "content" of consciousness, society is not yet prepared to define, diagnose and
      accept a "content" of consciousness-based standard of death, when this function
      is lost in isolation in PVS, advanced forms of dementia and anencephalics. I
      propose a concept of death that excludes those states taking in consideration the
      basic mechanisms of consciousness generation in human beings: "The irreversible
      loss of consciousness, considering both its capacity and its content". This
      definition of human death takes consideration as hallmarks, both components of
      consciousness which are essentially significant to the nature of man, to provide
      the functioning of the "organism as a whole".

PMID- 7562027
TI  - Lactate metabolism conducted by rat C6-glioma in the cells culture.
AB  - In order to investigate the lactate metabolism conducted by rat C6-glioma, the
      author incubated the C6-glioma cells in culture medium with oxygen and glucose,
      and measured the daily glucose and lactate concentrations in the cell culture
      fluid by using an electrode-based analyzer. The cells proliferated by the fourth
      culture day, saturated at the fifth or sixth days, and then the cell counts
      started to decrease. They died by the twelfth day. A large amount of the glucose
      was consumed within the first six culture days, while the lactate was produced
      during the same time periods in the medium solution having abundant oxygen. The
      lactate, however, started to be consumed from the seventh day. The author
      demonstrated in vitro that C6-glioma cells conducted anaerobic glycolysis in the
      glucose-rich aerobic culture condition, and consumed lactate in a
      hyperproliferative and low-glucose state, probably by using the glutamine
      oxidation.

PMID- 7562029
TI  - Automated percutaneous discectomy in herniated lumbar discs treatment: experience
      after the first 200 cases.
AB  - Two hundred patients presenting lumbo-sacral radicular pain were treated with
      automated percutaneous discectomy and were divided into two groups, on the ground
      of their symptomatology: group A included those patients that, otherwise, would
      undergo conservative therapy, because of their moderate pain; group B gathered
      patients whose severe pain needed undelayed surgery. The success rate that we
      reported in group A was 85%, while, in group B, it was 64%. Recurrences needing
      open surgery occurred in 15% of group B. Although characterized by delayed
      recovery, this technique seems to have good results even in so called surgical
      patients, in comparison with open surgery.

PMID- 7562028
TI  - Medulloblastoma in adults.
AB  - Seventeen adult patients (16 years of age and over) with medulloblastoma were
      managed at King Faisal Specialist Hospital and Research Centre between 1981 and
      1992. Nine patients were males and eight were females. The average age at
      diagnosis was 26.7 years; the females were younger than the males. The average
      duration of history before diagnosis was 14.5 weeks, the females presenting
      earlier than the males. The tumors were located in the midline (9) and the
      hemispheres (8). Nine patients had the desmoplastic variant and eight had
      standard primitive neuroectodermal tumor. Hydrocephalus developed in 14 of the
      patients only seven of whom required a shunting procedure. All patients had
      either subtotal or gross total removal of the tumor. Sixteen patients had
      postoperative radiation therapy; one patient refused radiation therapy. Two
      patients had chemotherapy following recurrence of the tumor. The clinical
      presentation, radiological studies, histological variants, treatment and outcome
      are discussed in this report.

PMID- 7562032
TI  - Spinal epidural meningiomas in childhood: a case report.
AB  - A case of a girl affected by an extradural spinal meningioma is described. This
      lesion is rare in childhood, and the prognosis may be not favorable. In our case
      a complete removal of the neoplasm with exeresis of the involved dura resulted in
      a very good clinical and radiological recovery.

PMID- 7562030
TI  - Intracranial nail. A case report.
AB  - Penetrating cranio-cerebral trauma caused by fire-arm constitute the most
      frequent penetrating wounds in civilian ambit; in these cases the great extention
      of cerebral damage is the result of distructive forces generated by high velocity
      which moves this bodies. In civilian ambit cranio-cerebral wounds caused by
      penetrating bodies, but moved by low cinetic energy are increasing constantly,
      due to the development of industrial activities. The cases reported in literature
      are few; in the present paper we present the case of a cranio-cerebral wound
      caused by a nail, which is the longest nail ever reported in literature (9 cm).
      Cranio-cerebral penetrating wounds caused by nail are reported only as curious
      experience; none authors tried to standard the medical-surgical approach as for
      what concern the clinic valutation, as for treatment. We think that for these
      traumatic event, we can adapt the same valutations criteria used for wounds
      caused by fire-arms. For what concerns surgery of such injuries, we consider the
      emergency operation the best solution; generally in these cases the purpose of
      surgery is not the removal of devitalized tissues, evacuation of hematomas or
      removal of bone fragments or of penetrating bodies as happen in cases of
      penetrating bodies moved by high cinetic energy, but for the possible
      complications which can result immediately or after the trauma.

PMID- 7562031
TI  - Spinal epidural abscess caused by Brucella: case report.
AB  - We report a case of a patient with symptoms and signs of sciatica, due to spinal
      epidural abscess caused by Brucella, which was diagnosed by Magnetic Resonance
      Image. The literature is reviewed and the radiological features, particularly
      magnetic resonance image findings, are analyzed.

PMID- 7562033
TI  - Intramedullary haemorrhage due to AVM located within the medulla oblongata in a
      three year old child. Case report.
AB  - Intramedullary arteriovenous malformations are rare in childhood. Yasargil
      reports only two cases in children under ten years of age out of a total of forty
      one cases of AVM operated on between 1967 and 1983 in which microsurgical
      techniques were used. The early symptoms of these lesions are those due to
      intramedullary or subarachnoid haemorrhage with neurological deficit, pain and/or
      weakness or numbness of one or more limbs. We report the case of an
      intramedullary haematoma due to arteriovenous malformation within the medulla
      oblongata in a three year old child admitted for cervical pain and right arm
      hypostenia. The CT scan and MRI showed an intramedullary expansive lesion with
      associated internal haematoma between C1-C7 level. Because of the rapid clinical
      deterioration upon the onset of right hemiparesis we procedeed to empty the
      intramedullary haematoma and to remove the intrabulbar AVM. A swift improvement
      of neurological deficit was observed along with a total regression of the
      symptomatology in a month's time. The excellent results reported in this case,
      very likely the only case in the literature occurring in a very small child at
      this spinal cord level, are mostly due to the early surgical treatment and to the
      exact information that MRI provided.

PMID- 7562034
TI  - Foramen magnum stenosis and bilateral benign subdural collections in
      achondroplasia: case report.
AB  - A case of achondroplasia is presented in which cervico-medullary junction
      compression by foramen magnum stenosis and generalized seizures by bilateral
      subdural effusions were relieved by suboccipital craniectomy with C1 laminectomy
      and drainage of the collections. The important role played by NMR in the
      diagnosis of foramen magnum stenosis is stressed; the possible causes of
      hydrocephalus and subdural collections in achondroplasic patients are discussed.
      According to the authors surgical drainage of benign subdural collections in
      these patients is indicated in case of intractable seizures.

PMID- 7562035
TI  - The radiopharmaceutical approval process: a day in the life.

PMID- 7562036
TI  - Vasoactive intestinal peptide receptor scintigraphy.
AB  - This study presents the biodistribution, safety and absorbed dose of 123I-VIP
      administered to 18 patients with intestinal adenocarcinomas or endocrine tumors.
      METHODS: To achieve high-specific activity, 123I-VIP was purified by HPLC.
      Following intravenous administration of 123I-VIP (172 +/- 17 MBq (4.65 +/- 0.5
      mCi); < 300 pmole ( < 1 microgram)/patient), sequential images were recorded
      during the initial 30 min. Thereafter, whole-body images were acquired in
      anterior and posterior views at various time points. Dosimetry calculations were
      performed on the basis of gamma camera data, urine, feces and blood activities.
      RESULTS: After injection of labeled peptide, the lung was the primary site of
      123I-VIP uptake. Peak lung activity represented 40% +/- 7% of the injected dose
      at 0.7 hr and declined to 21% +/- 7% at 3.5, to 14% +/- 3% at 7 and to 8% +/- 4%
      22 hr postinjection. Radioactivity was excreted into the urine and amounted to
      37% +/- 16% of the injected dose within 4, 68% +/- 12% within 8, 82% +/- 16%
      within 16 and 93% +/- 8% within 24 hr postinjection. The mean effective half-life
      of 123I-VIP in the lungs was 2.2 and 6 hr in the urinary bladder. The highest
      radiation absorbed doses were calculated for the lungs [67 muGy/MBq (248
      mrad/mCi)], urinary bladder [77 muGy/MBq (284 mrad/mCi)] and thyroid gland [104
      muGy/MBq (386 mrad/mCi)]. The effective dose was 28 muSv/MBq (104 mrem/mCi).
      CONCLUSION: HPLC-purified 123I-VIP shows favorable dosimetry and is a safe and
      promising peptide tracer for localization of tumors expressing receptors for VIP.

PMID- 7562037
TI  - Dual-isotope SPECT of skull-base invasion of head and neck tumors.
AB  - Skull-base invasions of head and neck tumors were examined by simultaneous bone
      and tumor dual-isotope SPECT (S-SPECT) with 99mTc-hydroxy-methylene-diphosphonate
      (99mTc-HMDP) and 201Tl-chloride. The effectiveness and reliability of tumor
      diagnosis by this method was the primary interest in this study. METHODS: Before
      S-SPECT imaging, a phantom experiment using dried skull-bone specimens was
      performed to establish anatomical details of the skull base with the SPECT
      camera. Radionuclide crosstalk, window widths and control patients were also
      examined prior to S-SPECT imaging. Twenty patients with suspected tumor invasion
      of the skull base underwent S-SPECT. RESULTS: Preliminary experiments revealed
      that crosstalk effects could be disregarded with adequate window width and
      routine administrative doses of the radionuclides. S-SPECT detected bone
      destruction and the extent of tumor invasion for all 12 patients in whom skull
      base involvement was diagnosed by CT or MRI. For the three patients in whom CT or
      MRI revealed no tumor invasion, the S-SPECT images did not show any abnormal
      accumulation in similar regions. In the remaining five patients without CT and
      MRI confirmation of skull-base invasion, the S-SPECT findings showed skull-base
      abnormalities in three. Tumor invasion was confirmed surgically or by clinical
      follow-up. The remaining two patients had negative S-SPECT images. CONCLUSION: S
      SPECT is an effective and reliable diagnostic technique for detecting tumor
      invasion in the complex bony regions of the skull base.

PMID- 7562038
TI  - Comparison of fluorine-18-fluorodeoxyglucose PET, MRI and endoscopy for staging
      head and neck squamous-cell carcinomas.
AB  - Accurate, preoperative assessment of tumor extent and lymph node involvement is
      mandatory for individualized therapy in patients with squamous-cell carcinomas
      (SCCs) of the head and neck region. Metabolic imaging, [18F]fluorodeoxyglucose
      (FDG) PET and MRI were compared with postoperative, histologic tissue
      characterization. METHODS: Dynamic and static PET with 370 MBq [18F]FDG up to 60
      min postinjection and MRI were compared prospectively in 22 patients with head
      and neck SCCs. PET results with and without attenuation correction were compared
      with postoperative T and N stages based on pathologic findings. RESULTS: Kinetic
      characteristics and tracer uptake intensity were similar in primary tumors and
      lymph node metastases. In both, FDG uptake did not reach a plateau phase 60 min
      postinjection. There was no statistically significant correlation of FDG uptake
      with plasma glucose level or histologic grading. All primary tumors were clearly
      demonstrated by PET, which tended to overestimate tumor size. The sensitivity and
      specificity for detecting individual lymph node involvement were 90% and 96%,
      respectively, for PET and, thus, significantly higher for MRI (78% and 71%,
      respectively; p < 0.05). N stages were correctly identified by MRI in only 4
      patients; PET correctly staged lymph nodes in 15 of 17 patients. Based on "neck
      sides", the sensitivity and specificity were higher for PET, 89% and 100%,
      respectively, compared with MRI values of 72% and 56%, respectively. CONCLUSION:
      FDG-PET may be helpful in detecting occult primary tumors with positive lymph
      nodes.

PMID- 7562039
TI  - Technetium-99m-sestamibi prone scintimammography to detect primary breast cancer
      and axillary lymph node involvement.
AB  - The purpose of this study was to evaluate prospectively the sensitivity and
      specificity of scintimammography in the detection of both primary breast cancer
      and axillary lymph node involvement. METHODS: Sixty-five consecutive women
      referred for a suspicious breast lesion on clinical examination and/or with
      abnormal mammographies suggestive of malignancies were studied with
      scintimammography using planar prone imaging (with a chest positioning device
      with semicircular lateral aperture on the imaging table) performed 15 min
      postinjection of 25-30 mCi 99mTc-sestamibi. Three planar views, right and left
      lateral prone and anterior supine thoracic views, were obtained (8-10 min/view).
      The entire breast and ipsilateral axillary region were included in the field of
      view. Excisional breast biopsy and/or fine needle aspiration cytology were
      performed in all patients within 4 wk after scintimammography. Axillary node
      dissection was also performed. RESULTS: The largest primary tumor measured 2 x 3
      cm. There were 47 primary breast cancers (8 different histologic types) and 18
      benign breast lesions (5 histologic types). The sensitivity of scintimammography
      for detecting primary breast cancer was 91.5% (43 true-positive, 4 false
      negative) and the specificity was 94.4% (17 true-negative, 1 false-positive).
      Metastatic axillary lymph node involvement was seen in 19 of 41 patients. The
      sensitivity of scintimammography to detect metastatic lymph nodes was 84.2% (16
      true-positive, 3 false-negative) and the specificity was 90.9% (20 true-positive,
      2 false-positive). CONCLUSION: This preliminary study confirms the results of
      some previous reports, which showed the high diagnostic accuracy of
      scintimammography in detecting breast cancer. This study also shows the potential
      value of this procedure to detect axillary lymph node involvement as concomitant
      information.

PMID- 7562041
TI  - Mammary lymphoscintigraphy in breast cancer.
AB  - Lymphoscintigraphy has previously been used to define lymph drainage patterns and
      locate sentinel lymph nodes, prior to surgery, in patients with cutaneous
      melanoma. The aim of this study was to apply this technique to patients with
      breast cancer using intramammary injections placed around the primary tumor in
      the breast. METHODS: Lymphoscintigraphy using 99mTc-labeled antimony sulphide
      colloid was performed in 34 patients with a suspected primary breast cancer.
      Images were recorded immediately and at 2.5 hr using a LFOV digital gamma camera.
      Sentinel lymph node location was marked when possible. RESULTS: Lymphatic
      drainage patterns were successfully recorded in all but three patients. Lymph
      drainage was to the axillary, internal mammary, supraclavicular and, in one
      patient, infraclavicular node fields in various combinations but always on the
      same side of the body as the breast tumor. There was unexpected drainage across
      the center line of the breast to axillary or internal mammary nodes in 32% of
      patients with inner or outer quadrant lesions. Direct drainage to supraclavicular
      or infraclavicular nodes occurred in 20% of upper quadrant lesions. Drainage to
      the ipsilateral axilla occurred in 85% of patients, where a single sentinel node
      was seen in all cases. CONCLUSION: Intramammary lymphoscintigraphy can be used to
      define the lymphatic drainage patterns of individual breast cancers. The surface
      location of sentinel lymph nodes in the draining node fields can be marked and in
      the axilla their depth can be measured. It should therefore be possible to use
      lymphoscintigraphy, along with a blue dye injection technique or the gamma probe
      at surgery, to locate sentinel lymph nodes in patients with breast cancer.

PMID- 7562040
TI  - Positron tomographic assessment of estrogen receptors in breast cancer:
      comparison with FDG-PET and in vitro receptor assays.
AB  - The purpose of this study was to assess the results of PET with 16 alpha
      [18F]fluoro-17 beta-estradiol (FES) and [18F]fluoro-2-deoxy-D-glucose (FDG) to
      validate the concordance between tumor estrogen-receptor (ER) status as
      determined by FES-PET and in vitro assays and to assess the relationship between
      tumor metabolic activity determined by FDG-PET and tumor ER status, both of which
      may provide information about tumor aggressiveness and prognosis. METHODS: We
      studied 32 patients with primary breast masses and 21 patients with clinical or
      radiological evidence of recurrent/metastatic breast carcinoma. A diagnosis of
      breast carcinoma was subsequently proven in 43 patients (24 primary, 15
      metastatic and 4 recurrent tumors). In vitro assessment of ER status was
      available for 40 malignant lesions (23 primary and 17 metastatic/recurrent). The
      patients underwent PET with both FES and FDG, and the uptake of each tracer
      within each lesion was evaluated qualitatively as well as semiquantitatively
      using the standardized-uptake-value (SUV) method. RESULTS: We found good overall
      agreement (88%) between in vitro ER assays and FES-PET. This degree of agreement
      is similar to that observed between replicate in vitro assays (with discordances
      due to interlaboratory, interassay and specimen variability). We were, however,
      unable to demonstrate any significant relationship between tumor FDG uptake and
      ER status or between tumor FDG and tumor FES uptake in these patients.
      CONCLUSION: These results indicate that in vitro ER assays and/or FES-PET provide
      unique direct information about breast cancer ER status that cannot be obtained
      indirectly by FDG-PET.

PMID- 7562042
TI  - Lymphoscintigraphy and the intraoperative gamma probe.

PMID- 7562043
TI  - Technetium-99m-sestamibi scintimammography of breast lesions: clinical and
      pathological follow-up.
AB  - Mammography and physical examination combined have a sensitivity of 85% for the
      detection of breast carcinoma. Mammography also has a positive predictive value
      of 15%-30%. The aim of this study was to evaluate the usefulness of
      scintimammography using 99mTc-sestamibi as a complementary technique to
      mammography for the detection of breast carcinoma to improve mammography's
      sensitivity and specificity. METHODS: We studied 100 consecutive patients (mean
      age 48.3 +/- 10.8 yr) who had 106 lesions warranting biopsy (67 lesions) or fine
      needle aspiration cytology (FNA) (39 lesions) of the breast. There were 85
      palpable and 21 nonpalpable lesions. The size of the lesions on the mammograms
      were moderate (2.3 +/- 1.8 x 1.9 +/- 1.5 cm). Each patient received 20 mCi 99mTc
      sestamibi intravenously. Five and 60 min postinjection, planar breast images in
      the lateral prone position were obtained. An anterior erect projection was then
      obtained to visualize the axilla and, if needed, a posterior oblique prone
      projection. RESULTS: Scintimammography was true-positive in 30 lesions with
      biopsy-confirmed breast carcinoma; it was true-negative in 65 lesions
      subsequently proved to be benign. There were nine breast lesions with benign
      findings in which the scintimammography result was positive (false-positive
      scintimammography) for cancer. Finally, two lesions with pathologically proven
      carcinomas demonstrated a negative scintimammographic result. Therefore, in this
      group, the sensitivity of scintimammography was 93.7% with a specificity of
      87.8%; the positive predictive value was 76.9%. The negative predictive value was
      97%. CONCLUSION: Scintimammography is a highly sensitive test that improves the
      specificity of conventional mammography for the detection of breast carcinoma.

PMID- 7562044
TI  - Predicting malignancy grade with PET in non-Hodgkin's lymphoma.
AB  - Our goal was to determine whether PET with 11C-methionine and/or 18FDG could
      predict malignancy grade in non-Hodgkin's lymphoma (NHL). METHODS: Twenty-three
      patients with high-grade, low-grade or transformed low-grade NHL were
      investigated. Standardized uptake values (SUV), transport rate and mass influx
      values were calculated both for the whole tumor [mean regions of interest, (ROI)]
      and for the tumor area with the highest levels of activity, comprising four
      contiguous pixels within each tumor and designated as a hot spot. RESULTS: Both
      11C-methionine and 18FDG detected all tumors. In addition, 18FDG discriminated
      between high- and low-grade NHL, whereas 11C-methionine did not. With 18FDG,
      three transformed low-grade NHLs behaved in an intermediate manner. All
      quantitative uptake values correlated well with each other for both tracers,
      except for the mean ROI SUV and transport rate of 11C-methionine. Quantifications
      of mean ROI uptake and hot spots were strongly correlated. CONCLUSION: The
      results of this study together with previous findings from other studies indicate
      that 18FDG but not 11C-methionine can predict malignancy grade in NHL. Further
      studies with a larger series of patients are needed.

PMID- 7562045
TI  - Axillary lymph node uptake of technetium-99m-MDP.
AB  - We sought to determine the frequency and significance of axillary lymph node
      visualization on bone scans performed with diphosphonates. METHODS: Consecutive
      99mTc-methylene diphosphonate (99mTc-MDP) bone scans (2435) were inspected for
      axillary soft-tissue uptake. In positive cases, the results of physical
      examination, correlative imaging studies and serial bone scans were recorded, as
      was the site of venipuncture. RESULTS: Forty-eight studies (2%) showed axillary
      uptake ipsilateral to the injection site. Extravasation of tracer, documented by
      focal activity near the injection site, was present in every case. There was no
      association with axillary adenopathy, mass, induration or radiographically
      visible calcification. On some images, foci adjacent to the axilla were
      superimposed on the rib, scapula, or humerus. The bone-to-background ratio was
      frequently reduced; repeat imaging after 1-2 hr usually improved osseous detail.
      CONCLUSION: Ipsilateral axillary lymph node visualization due to extravasation of
      99mTc-MDP is frequently associated with additional foci superimposed on osseous
      structures simulating pathology. Delayed skeletal uptake is common in such cases
      and necessitates a greater time interval between injection and imaging.

PMID- 7562047
TI  - Carbon-11-methionine PET imaging of malignant melanoma.
AB  - The purpose of the study was to assess the feasibility of PET and L-[methyl
      11C]methionine (11C-methionine) in the detection of malignant melanoma. METHODS:
      Ten patients diagnosed with malignant melanoma (two with primary melanoma and
      eight with metastatic melanoma of the skin) but had no liver metastases underwent
      a PET study before starting cancer therapy. Dynamic scanning was performed for 40
      min in seven patients and 10-20 min in three patients 25-45 min postinjection.
      RESULTS: Carbon-11-methionine PET detected all melanoma lesions greater than 1.5
      cm (n = 22) in diameter, whereas five smaller pulmonary lesions were not
      detected. The average standardized uptake value of the untreated lesions was 6.3
      +/- 2.1 (n = 19) and the uptake rate (influx constant) was 0.085 +/- 0.041 min-1
      (n = 16). CONCLUSION: PET imaging with 11C-methionine is an effective method for
      visualizing melanoma. It may also be useful in measuring tumor metabolic activity
      in vivo.

PMID- 7562046
TI  - Technetium-99m-labeled antigranulocyte antibody bone marrow scintigraphy.
AB  - Although bone scintigraphy is a sensitive method for detecting skeletal
      metastases, it is often equivocal for metastases due to poor specificity. This
      study evaluates 99mTc-antigranulocyte antibody (AGA) bone marrow scintigraphy in
      differentiating malignant from benign lesions, in 42 patients with skeletal
      tumors who had equivocal bone scans. METHODS: AGA scans performed approximately 1
      wk after 99mTc-MDP bone imaging were visually assessed for the presence of
      concordant marrow defects. Final diagnoses were made from radiological results,
      follow-up bone scans or clinical evaluation for 12 mo or longer. RESULTS: The
      final diagnoses were: skeletal metastasis (19 patients), no metastasis (20
      patients) and unconfirmed (3 patients). AGA scans could not determine the
      presence of a concordant defect in three patients because of overlying liver
      activity or previous irradiation of the region. Seventeen patients had bone
      marrow defects concordant with bone scan lesions, whereas 15/19 patients without
      metastasis had normal AGA scans. The sensitivity and specificity of AGA for
      detecting skeletal metastases were 100% and 79%, respectively. CONCLUSION: AGA
      scans had a low incidence of skeletal metastases in patients who had equivocal
      bone scans. Although a concordant marrow defect increases the possibility of
      metastasis, further radiological investigation to exclude benign disease is
      warranted.

PMID- 7562048
TI  - In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG
      PET.
AB  - The present study was designed to assess glucose metabolism in hepatocellular
      carcinoma (HCC) with PET and [18F]fluorodeoxyglucose (FDG) and to compare the
      results with the measured in vitro enzymatic activity of glucose metabolism and
      the histologic grading of HCC. METHODS: Dynamic FDG-PET scans were obtained in 17
      preoperative patients with HCC. From the serial tissue and arterial
      radioactivities obtained by dynamic PET, FDG kinetic rate constants (K1 to k4)
      were obtained. The standardized uptake value (SUV) was also determined from the
      images acquired 48 to 60 min after FDG administration. These PET results were
      compared with hexokinase and glucose-6-phosphatase (G6Pase) activities and
      histologic grading of HCC in surgically resected tumor materials. According to
      histologic grading, the tumors were divided into low-grade and high-grade HCCs.
      RESULTS: The k3 and SUV of high-grade HCCs were significantly higher than those
      of low-grade HCCs (p < 0.005, each). In addition, high correlations were observed
      between the hexokinase activities and these two parameters (r = 0.715 0.768,
      respectively). In some HCCs, relatively high G6Pase activities and k4 values
      modified tumor FDG uptake. CONCLUSION: FDG PET is a valuable method for assessing
      glucose metabolism and histologic grading of HCC.

PMID- 7562049
TI  - RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper
      64-labeled monoclonal antibody.
AB  - Detection of tumor foci may be improved by combining the selective tumor
      targeting properties of a monoclonal antibody with the superior sensitivity and
      contrast resolution of PET. METHODS: An anti-colorectal carcinoma monoclonal
      antibody (MAb 1A3) was labeled with 64Cu, a positron-emitting radionuclide, by
      use of a bifunctional chelate (bromoacetamidobenzyl-TETA) and evaluated in 36
      patients with suspected advanced primary or metastatic colorectal cancer. After
      radiopharmaceutical injection (5-20 mg protein, 10 mCi 64Cu), PET was performed
      once or twice, 4 to 36 hr later. All patients had CT scans and 18 patients were
      also studied with [18F]fluorodeoxyglucose (FDG) PET. RESULTS: In 29 patients, one
      or more tumor sites (n = 56) were proven, in 5 patients the absence of active
      tumor was confirmed and in the remaining 2, tumor status is not yet confirmed. Of
      the 56 confirmed tumor sites, 40 were detected by MAb-PET as foci of increased
      activity (sensitivity 71%). The positive predictive value of MAb-PET was
      excellent, ranging from 89% (40/45) to 96% (43/45), depending on the ultimate
      classification of three image-positive, but as yet unconfirmed tumor sites. Also,
      MAb-PET detected 11 new occult tumor sites, including 9 small abdominopelvic foci
      less than 2.0 cm in diameter that were not detected by CT or MRI. There were no
      complications, but significantly elevated HAMA titers were found in 28% of the 29
      patients tested 1 to 12 mo after injection. There was no apparent dose-related
      effect from 5 to 20 mg MAb 1A3. CONCLUSION: These Phase I/II results suggest that
      PET with radiolabeled MAbs (radioimmunoPET) may have important applications in
      clinical oncology, particularly for detecting smaller colorectal tumor foci in
      the abdomen or pelvis and for determining accurate dosimetry.

PMID- 7562050
TI  - Neuropeptide receptors in health and disease: the molecular basis for in vivo
      imaging.

PMID- 7562051
TI  - SUV: standard uptake or silly useless value?

PMID- 7562052
TI  - Localization of an ectopic parathyroid adenoma by double-phase technetium-99m
      sestamibi scintigraphy.
AB  - Double-phase planar scintigraphy using 99mTc-MIBI has been introduced as a means
      to detect and localize parathyroid adenomas. Focal uptake on both early and
      delayed imaging is typical of these entities. We report a patient with persistent
      hypercalcemia following subtotal parathyroidectomy, who was found
      scintigraphically to have an ectopic parathyroid adenoma. Following initial
      detection within the mediastinum using planar scintigraphy, the adenoma was more
      precisely localized using SPECT imaging. This case suggests that double-phase
      parathyroid planar scintigraphy augmented with SPECT imaging, if needed, is cost
      effective, and often necessary, in the assessment of primary hyperparathyroid
      patients before surgical reexploration.

PMID- 7562053
TI  - Cervical lymph node metastasis of thyroid papillary carcinoma imaged with
      fluorine-18-FDG, technetium-99m-pertechnetate and iodine-131-sodium iodide.
AB  - A 49-yr-old white woman with diffuse sclerosing variant of papillary carcinoma of
      the thyroid revealed abnormal [18F]FDG accumulation within cervical lymph node
      metastases prior to thyroidectomy. The abnormal cervical foci of glucose
      metabolism corresponded to similar areas of abnormal [99mTc]pertechnetate and
      radioiodine accumulation on presurgical scans. The primary thyroid tumor within
      the thyroid gland was not delineated as a focal defect on any of the three
      imaging studies. The relative thyroid-to-background soft-tissue ratio in the
      [18F]FDG study, however, appeared higher than usual. As with 131I and
      [99mTc]pertechnetate, this case demonstrates that [18F]FDG PET can detect
      cervical lymph node metastases in the preoperative thyroid cancer patient.

PMID- 7562054
TI  - In vitro identification of vasoactive intestinal peptide receptors in human
      tumors: implications for tumor imaging.
AB  - In vitro receptor measurements in tumors were performed to evaluate the potential
      of the vasoactive intestinal peptide receptor (VIP-R) as an imaging tool in human
      cancer. METHODS: Three hundred thirty-nine human tumors were investigated for
      their VIP-R content by in vitro receptor autoradiography on tissue sections with
      125I-VIP. For comparison, somatostatin receptors (SS-R) were measured in adjacent
      sections of these tumors with 125I-[Tyr3]-octreotide. RESULTS: VIP-R were
      characterized and localized in the neoplastic cells of most breast carcinomas,
      breast cancer metastases, ovarian adenocarcinomas, endometrial carcinomas,
      prostate cancer metastases, bladder carcinomas, colonic adenocarcinomas,
      pancreatic adenocarcinomas, gastrointestinal squamous cell carcinomas, non-small
      cell lung cancers, lymphomas, astrocytomas, glioblastomas and meningiomas. Among
      neuroendocrine tumors, all differentiated and one-half of undifferentiated
      gastroenteropancreatic tumors, pheochromocytomas, small-cell lung cancers,
      neuroblastomas and inactive pituitary adenomas were found to express VIP-R. In
      general, VIP-R were found much more frequently than SS-R, but only 5 of 19 growth
      hormone-producing adenomas and no medullary thyroid carcinomas or Ewing sarcomas
      had VIP-R. In all tumors tested, the VIP-R were of high affinity and specific for
      VIP and pituitary adenylate cyclase-activating peptide. No cross-competition
      between VIP and SS could be identified. CONCLUSION: Most human carcinomas express
      VIP-R, as measured by in vitro receptor autoradiography. These data represent the
      molecular basis for evaluation of VIP-R imaging of these tumors in vivo and
      predict its great potential value.

PMID- 7562055
TI  - Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: I.
      Are inflammatory cells important?
AB  - To investigate the contribution of various tumor components to tumor [3H]FDG
      uptake, the size of proliferative cell and macrophage populations and the extent
      of necrosis, inflammatory infiltration and granulation tissue formation were
      evaluated in syngeneic rat mammary cancers (RMC) grown in immunocompetent rats,
      an animal tumor model that closely mimics human breast carcinoma. METHODS: Tissue
      components of breast cancers grown in female Lewis rats (n = 6) were identified
      histologically and immunohistochemically. Tracer uptake was studied by
      quantitative autoradiography 2 hr after an intravenous injection of 100 muCi
      [3H]FDG. RESULTS;: RMC tumors were glandular, with small foci of necrosis and
      were surrounded by a thin layer of granulation tissue. Tumors retained
      approximately 4% of the injected FDG dose (1.9 +/- 0.27 muCi/g). Macrophages
      numbered 0.5% of total cancer cells (1.2 +/- 1.0 of 246 +/- 77) and 18.0% +/-
      3.9% of the nuclei of cancer cells were proliferating cell nuclear antigen (PCNA)
      positive (52 +/- 27 of 293 +/- 55). FDG uptake (in apparent disintegrations per
      minute per microgram of protein) in the cancer cell was 47.3 +/- 5.6, with the
      highest uptake in foci of high tumor cell density (82.1 +/- 6.3). Lower levels of
      FDG uptake were found in necrotic areas (19.8 +/- 22.9), granulation tissue (26.9
      +/- 9.2) and areas of inflammatory infiltration (20.5 +/- 15.5). CONCLUSION:
      These data suggest that FDG-PET imaging of untreated breast cancer mainly
      reflects tracer uptake in cancer cells.

PMID- 7562056
TI  - Autoradiography and radioscintigraphy of technetium-99m-sestamibi in c-neu
      transgenic mice.
AB  - Intratumor distribution patterns of 99mTc-sestamibi and 14C-2-deoxy-D-glucose
      were compared in the c-neu OncoMouse, a transgenic mouse that spontaneously
      develops breast tumors. METHODS: Thirty or 60 min after intravenous injection of
      5 muCi 14C-2-deoxy-D-glucose and 3 mCi 99mTc-sestamibi into mice (n = 3 per time
      point) bearing mammary tumors (0.3-1.5 cm), the animals were analyzed for organ
      and tumor distribution using dual-label, whole-body autoradiography. The
      retention patterns of the two compounds were related to tumor morphology and
      viability, based on H&E-stained adjacent sections. For imaging studies, the
      transgenic mice (n = 9) were anesthetized with pentobarbital, injected
      intravenously with 5-20 mCi 99mTc-sestamibi and imaged for 60 min using a gamma
      camera equipped with a 1-mm pinhole collimator. RESULTS: All positively stained
      tumors retained both agents, with a mean 99mTc-sestamibi tumor retention of 0.38%
      +/- 0.2% ID/g at 30 min compared to 4.18% +/- 0.62% ID/g for 14C-2-deoxy-D
      glucose. Tumor retention of the agents remained the same at 60 min, and neither
      compound localized within necrotic or cystic regions of the neoplasms. Repeat
      imaging at 2-8-day intervals indicated a predicted sensitivity to detect a 30%
      difference in tumor retention of a test versus reference compound in preclinical
      screening. CONCLUSION: The c-neu OncoMouse is a useful model for in vivo imaging
      and provides a spontaneous tumor model for preclinical screening of breast tumor
      imaging agents.

PMID- 7562057
TI  - Fluorine-18-fluorodeoxyglucose-guided breast cancer surgery with a positron
      sensitive probe: validation in preclinical studies.
AB  - In this study, the feasibility of utilizing 2-deoxy-2-fluoro-d-glucose (FDG) in
      conjunction with a positron-sensitive intraoperative probe to guide breast tumor
      excision was investigated. METHODS: The probe was constructed with a plastic
      scintillator tip coupled to a photomultiplier tube with fiber optic cable.
      Anticipated resolution degradation was evaluated by measurement of line spread
      functions in the presence of background radiation. Realistic photon background
      distributions were simulated with a human torso phantom and a cardiac insert. The
      relationship between resolution and energy threshold was measured to find the
      optimal discriminator settings. In addition, probe sensitivity as a function of
      energy threshold was determined for various size-simulated tumors. Finally, the
      ability to localize breast cancers in vivo was tested in a rodent model. Mammary
      rat tumors implanted in Lewis rats were examined after injection with FDG; these
      results were correlated with those of histologic analyses. RESULTS: Measurements
      of line spread functions indicated that resolution could be maximized in a
      realistic background photon environment by increasing the energy threshold to
      levels at or above the Compton continuum edge (340 keV). At this setting, the
      probe's sensitivity was determined to be 58 and 11 cps/muCi for 3.18- and 6.35-mm
      diameter simulated tumors, respectively. Probe readings correlated well with
      histologic results: the probe was generally able to discriminate between tumor
      and normal tissue. CONCLUSION: This study indicates that breast cancer surgery
      guided by a positron-sensitive probe warrants future evaluation in breast
      conserving surgery of patients with breast cancer.

PMID- 7562059
TI  - Presurgical visualization of primary breast carcinoma with PET emission and
      transmission imaging.
AB  - The aim of this study was to investigate a technique that visualizes findings
      from PET images in a context useful for surgery. METHODS: Simultaneously acquired
      PET emission and transmission scans were used. By applying a multipurpose
      imaging, registration and rendering tool (MPM), displays of orthogonal and volume
      rendered views or any combination thereof were obtained. The PET emission and
      transmission scans were acquired under routine conditions. The final user
      customized display (with a combination of orthogonal cuts and rendered views) was
      processed in 10 min or less on commercially available hardware. Distinct features
      of the body shape were clearly visible on the volume-rendered transmission views.
      Hot spots, e.g., in primary breast cancer, from the emission scans could be
      easily assessed in their localization relative to the body outline. CONCLUSION:
      Rendering of the main signatures in a single comprehensive display makes this
      method potentially valuable for simple presurgical workup and therapeutic
      management of breast cancer.

PMID- 7562058
TI  - Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)
      insulin visualizes human hepatocellular carcinomas.
AB  - Human hepatocellular carcinoma (HCC) is the most frequent primary hepatic
      malignancy and its diagnosis by conventional methods is still difficult. We
      hypothesized that the expression of specific receptors could possibly be used to
      improve in vivo localization of HCC with specific receptor-based radioligands.
      METHODS: In initial in vitro studies, receptor binding of 99mTc-galactosyl
      neoglycoalbumin (99mTc-NGA) and 123I-Tyr-(A14)-insulin to HCC was investigated.
      Scintigraphy was performed in 45 patients with histologically confirmed HCC using
      either 99mTc-NGA (75-150 MBq; 25-50 nmole, n = 27) and/or 123I-Tyr-(A14)-insulin
      (100-150 MBq; 7.5-10 micrograms, n = 30). RESULTS: HCC (1256 +/- 290 pmole
      bound/mg protein, Kd = 3.4 +/- 2.9 nM) expressed a 1000-fold higher number of
      specific receptors for 123I-Tyr-(A14)-insulin compared to normal liver tissue
      (2.4 +/- 0.8 pmole bound/mg protein, Kd = 4.2 +/- 2.4 nM), whereas HCC did not
      express receptors specific for 99mTc-NGA. All HCC lesions were identified as cold
      spots after injection of 99mTc-NGA, whereas 123I-Tyr-(A14)-insulin accumulated in
      these lesions, indicating HCC-to-normal liver ratios of 1.6 +/- 0.4 in the mean.
      Subtraction images obtained from planar studies visualized 123I-Tyr-(A14)-insulin
      in HCC lesions detected by 99mTc-NGA as cold spots. CONCLUSION: This hepatocyte
      receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)
      insulin could become clinically useful in the diagnosis of HCC.

PMID- 7562060
TI  - Development of a SPECT-based three-dimensional treatment planning system for
      radioimmunotherapy.
AB  - Two major obstacles in the development of improved methods for more accurate dose
      estimates for radioimmunotherapy have been the difficulty in obtaining an
      accurate patient-specific three-dimensional activity map in vivo and calculating
      the resulting absorbed dose. We propose a method for three-dimensional internal
      dosimetry that integrates the three-dimensional activity map from SPECT with a
      dose-point kernel convolution technique to provide the three-dimensional
      distribution of absorbed dose. METHODS: Accurate activity quantitation was
      achieved with appropriate methods. The count density map from SPECT images was
      converted into an activity concentration map with a calibration phantom approach.
      This map was then convolved with an 131I dose-point kernel and three-dimensional
      fast Fourier transform to yield three-dimensional distribution of absorbed dose,
      which was then processed to provide the absorbed dose distribution in regions of
      interest. RESULTS: The accuracy of quantitative SPECT was validated to be within
      16%. The calculated penetrating radiation absorbed dose was verified with
      thermoluminescent dosimeter measurements to be within 8%. With standard organs
      and configuration, the method calculated absorbed dose in good agreement with the
      MIRD formalism (less than 14%). CONCLUSION: This method overcomes the limitations
      of planar imaging techniques and the current routine implementation of the MIRD
      formalism. The results can be processed to provide the absorbed dose distribution
      in regions of interest and parameters for treatment optimization. Absorbed dose
      distribution from any plane can be graphically displayed in various ways.

PMID- 7562061
TI  - Filtered technetium-99m-sulfur colloid evaluated for lymphoscintigraphy.
AB  - Several 99mTc-labeled radiopharmaceuticals have been developed for
      lymphoscintigraphy of the extremities. In the United States, however, these
      agents are not widely used clinically. This study evaluates the use of smaller
      particle sizes ( < 0.1 micron) of 99mTc-sulfur colloid (99mTc-SC) for
      lymphoscintigraphy. METHODS: The 99mTc-SC was prepared by kit, and the final
      preparation was filtered through a sterile 0.1-micron filter. The radiochemical
      purity (RCP) of the filtered 99mTc-SC was determined before administration.
      Nineteen patients with suspected lymphedema were injected with 18.5 MBq (500
      muCi) filtered 99mTc-SC intradermally in each foot, and whole-body images were
      obtained immediately and 1, 3, 6 and 24 hr later. Local views over the inguinal
      or axillary lymph nodes were also obtained every 5 min for the first hour.
      RESULTS: The average RCP value was 93.4% +/- 4.2% (n = 19), and the RCP
      difference pre- and postfiltration of the 99mTc-SC preparation was -1.7% +/- 1.4%
      (n = 40). Evaluation of the particle size with the polycarbonate filter showed
      that 89.9% +/- 4.5% (n = 28) of particles were less than 50 nm, and the particle
      size was further determined by electron microscopy to be 38.0 +/- 3.3 nm (n =
      202). The mean particle sizes of two peaks measured by laser light scattering
      techniques were 7.5 and 53.9 nm (major peak). Clinical studies with filtered
      99mTc-SC demonstrated similar lymphoscintigrams compared with those obtained with
      99mTc antimony sulfide colloid (99mTc-ATC). Filtered 99mTc-SC showed a faster
      transport rate to the inguinal lymph nodes and lower radiation dosimetry for
      liver, spleen and whole body compared with 99mTc-ATC. CONCLUSION: Filtered 99mTc
      SC can be easily prepared and is readily available for routine clinical use in
      lymphoscintigraphic studies.

PMID- 7562062
TI  - Relationships between tumor size and curability for uniformly targeted therapy
      with beta-emitting radionuclides.
AB  - Targeted radionuclide therapy is a new form of radiotherapy that differs in some
      important respects from external beam irradiation. One of the most important
      differences is due to the finite range of ionizing beta particles emitted as a
      result of radionuclide disintegration. The effects of particle range have
      important implications for the curability of tumors. METHODS: We used a
      mathematical model to examine tumor curability and its relationship to tumor size
      for 22 beta-emitting radionuclides that may have therapeutic potential. The model
      assumed a uniform distribution of radionuclide throughout. RESULTS: For targeted
      radionuclide therapy, the relationship between tumor curability and tumor size is
      different from that for conventional external beam radiotherapy. With targeted
      radionuclides, there is an optimal tumor size for cure. Tumors smaller than the
      optimal size are less vulnerable to irradiation from radionuclides because a
      substantial proportion of the disintegration energy escapes and is deposited
      outside the tumor volume. CONCLUSION: We found an optimal tumor size for
      radiocurability by each of the 22 radionuclides considered. Optimal cure
      diameters range from less than 1 mm for short-range emitters such as 199Au and
      33P to several centimeters for long-range emitters such as 90Y and 188Re. The
      energy emitted per disintegration may be used to predict optimal cure size for
      uniform distributions of radionuclide.

PMID- 7562063
TI  - Radioimmunotherapy of micrometastases: sidestepping the solid-tumor hurdle.

PMID- 7562064
TI  - Direct labeling of monoclonal antibodies with technetium-99m by photoactivation.
AB  - Direct radiolabeling methods currently rely on the addition of exogenous chemical
      reagents to create the necessary binding sites for 99mTc binding to monoclonal
      antibodies (MAbs). This work describes the use of ultraviolet (UV) light to
      facilitate photoactivation of MAbs for 99mTc radiolabeling. METHODS: The
      parameters of exposure wavelength and solution composition were investigated to
      provide a basis for further development. Based on these results, various murine
      MAbs and a chimeric MAb were photoactivated using a 300-nm (nominal) wavelength,
      eight-lamp (3.9 W each) photochemical reactor providing exposure for defined time
      periods. The MAb preparations were stored frozen and subsequently labeled by the
      addition of pertechnetate. For MAb-170, the photoactivated preparation was
      compared to a stannous ion reduced preparation by radiochemical (radiolabeling
      yield, serum stability cysteine challenge), biochemical (SDS-PAGE, IEF, SE-HPLC)
      and immunochemical (immunoreactivity) assays and biodistribution studies in mice.
      RESULTS: Photoactivation produced high radiolabeling yields for all the MAbs
      studied and MAb-170 produced comparable in vitro quality control profiles and in
      vivo biodistribution data. CONCLUSION: The use of this relatively simple, short
      and easily controlled photoactivation process for MAbs facilitates facile
      radiolabeling with 99mTc and provides an alternative to the direct chemical
      radiolabeling procedures.

PMID- 7562065
TI  - Generalized approach to absorbed dose calculations for dynamic tumor and organ
      masses.
AB  - Tumor absorbed dose calculations in radionuclide therapy are presently based on
      the assumption of static tumor mass. This work examines the effect of dynamic
      tumor mass (growth and/or shrinkage) on the absorbed dose. METHODS: Tumor mass
      kinetic characteristics were modeled with the Gompertz equation to simulate tumor
      growth and an additional exponential term to accommodate tumor shrinkage that may
      result as a consequence of therapy. RESULTS: Correction factors, defined as the
      ratio of the absorbed dose, which was calculated by considering tumor mass
      dynamics, to the absorbed dose, which was calculated by assuming static mass, are
      presented for 1- and 100-g tumors with different tumor mass kinetics. The
      dependence of the correction factor on the effective half-life Te of the
      radioactivity in the tumor and the tumor shrinkage half-time Ts was examined. The
      correction factors for the 1-g tumor were > 1 for short Ts and Te. In contrast,
      the correction factor was less than 1 for long Ts ( > 9 days). The dose
      correction factors for the 100-g tumor were > 1 for all Ts and Te. Finally, the
      dosimetric method for dynamic masses is illustrated with experimental data on
      Chinese hamster V79 multicellular spheroids that were treated with 3H.
      CONCLUSION: Correction factors as high as about 10 are likely when Te and Ts are
      short. As Ts increases beyond 20 days, the importance of dynamic mass diminishes
      because most of the activity decays before the mass changes appreciably. In some
      cases, mass dynamics should be taken into account when the absorbed dose to
      tumors is estimated.

PMID- 7562066
TI  - Rapid washout of technetium-99m-MIBI from a large parathyroid adenoma.

PMID- 7562067
TI  - Scintimammography: magic bullet or false promise.

PMID- 7562068
TI  - Disseminated bone marrow metastases from primary breast cancer: detection and
      follow-up by radioimmune bone marrow scintigraphy.

PMID- 7562069
TI  - Nobel laureates foretell future based on past achievements.

PMID- 7562070
TI  - The evolution of nuclear medicine.

PMID- 7562071
TI  - The anatomy of a competency.
AB  - In response to the Joint Commission on Accreditation of Healthcare Organization
      (JCAHO) standards, many educators are involved in implementing competency-based
      orientation as a format for assessing and validating competence. Written
      competencies are the tools of this important process. The purpose of this article
      is to help educators understand the basic elements of a competency and show them
      how to develop a well written competency. Suggestions for validating initial and
      continued competence are also included.

PMID- 7562072
TI  - Assessment of satisfaction with computer training in a healthcare setting.
AB  - The use of computers in healthcare settings has become increasingly common.
      However, issues of training and training assessment have received scant
      attention. The main aim of the current study was to assess the use of consumer
      satisfaction data for evaluation and development of computer training packages in
      healthcare settings. One hundred and thirty-six randomly selected people
      completed a brief satisfaction questionnaire at the completion of computer
      training. The effects of different teachers, course duration, course complexity,
      and changes in satisfaction over time were examined. The use of a customer
      satisfaction approach to training evaluation is discussed.

PMID- 7562073
TI  - Code 50: an orientation matrix to track orientation cost.
AB  - Estimates of staff orientation costs can range from $20,000-50,000 per person.
      The Director of Finance and the Director of Nursing Education and Research
      developed a system to track the orientation process to determine the actual
      costs. Head nurses and educators approached the orientation process differently;
      therefore, there was no consistency as to the time allotted for orientation.
      Although competency-based orientation tools were used for all new orientees, the
      average amount of time for new orientees to become productive ranged from 3-9
      months. By creating the orientation matrix, a unique pay class (code 50) was
      assigned for all new orientees, and a computer program was developed to track
      costs. The overtime hours for orientees dropped to 159 from 941, resulting in an
      83% reduction in overtime hours. The matrix ensured a more cost effective
      approach to orientation.

PMID- 7562074
TI  - Developing workplace advocacy behaviors.
AB  - In this article, the authors describe the concept of workplace advocacy,
      workplace hazards experienced by hospital nurses, methods for teaching workplace
      advocacy behavior, and strategies for controlling specific workplace hazards.
      Workplace advocacy is a universally applicable concept for maintaining
      professional nursing practice. Staff development educators are key in helping
      staff nurses achieve autonomous nursing practice.

PMID- 7562075
TI  - Teaching ethics to nurses.
AB  - Educating nurses about ethics is more complex, multidimensional, and time
      consuming than educating nurses about technical skills. Many factors, including
      the ability of the nurse to view situations holistically, the moral development
      of the nurse, and the institution's ethics, are involved. To illustrate how to
      teach nurses ethics, two examples of programs are detailed in this article.

PMID- 7562076
TI  - The real meaning of the restraint-free environment.

PMID- 7562077
TI  - Pain management: an innovative educational approach.

PMID- 7562078
TI  - Dietary medium-chain fatty acids raise and (n-3) polyunsaturated fatty acids
      lower hepatic triacylglycerol synthesis in rats.
AB  - The hypothesis tested was that dietary medium-chain or (n-3) polyunsaturated
      fatty acids, when compared with (n-6) polyunsaturated fatty acids, alter plasma
      triacylglycerol levels by affecting hepatic triacylglycerol synthesis as
      reflected by the activities of acetyl-CoA carboxylase, fatty acid synthase and
      diacylglycerol acyltransferase in liver. In two separate experiments rats were
      fed purified diets containing (n-6) polyunsaturated fatty acids in the form of
      corn oil and either (n-3) polyunsaturated fatty acids in the form of fish oil or
      medium-chain triacylglycerols (MCT). Consumption of MCT significantly raised
      plasma triacylglycerol concentrations, whereas fish oil feeding had a lowering
      effect compared with the corn oil-fed group. In individual rats, the hepatic
      triacylglycerol concentration was directly correlated with the plasma
      triacylglycerol concentration (r = 0.60, P < 0.001). The MCT oil diet vs. the
      corn oil diet markedly raised the activities of hepatic acetyl-CoA carboxylase,
      fatty acid synthase and diacylglycerol acyltransferase. In the rats fed fish oil,
      the activities of fatty acid synthase and diacylglycerol acyltransferase were
      significantly reduced, whereas the activity of acetyl-CoA carboxylase was not
      affected relative to activities in rats fed corn oil. The activities of the three
      enzymes were directly correlated with plasma triacylglycerol concentrations in
      individual rats (r = 0.60-0.75, P < 0.001). The type of fat in the diet probably
      affects the rate of hepatic triacylglycerol synthesis which is an important
      determinant of plasma triacylglycerol concentrations.

PMID- 7562080
TI  - Rat cecal inocula produce different patterns of short-chain fatty acids than
      fecal inocula in in vitro fermentations.
AB  - The effects of bacterial collection site, bacterial adaption to substrate and
      duration of fermentation on short-chain fatty acid (SCFA) production were studied
      using an in vitro fermentation system. Cecal and fecal inocula from rats fed
      purified diets containing 100 g/kg dietary fiber from canned peas or psyllium
      seed husk, or a nonpurified diet containing 170 g/kg dietary fiber fermented
      ileal excreta from colectomized rats fed a purified diet containing 100 g/kg
      dietary fiber from canned peas. The SCFA concentration, measured by gas
      chromatography, in anaerobic fermentations of 0, 3, 6, 12, 24, 48, 72 and 96 h,
      increased (P < 0.05) through 72 h. Compared with fecal inocula, cecal inocula
      produced SCFA at greater (P < 0.05) initial rates, more (P < 0.05) total SCFA and
      a greater (P < 0.05) proportion as n-butyrate. Inocula from rats fed the pea or
      nonpurified diets produced SCFA at greater (P < 0.05) molar proportions as
      acetate and less (P < 0.05) as propionate than inocula from rats fed psyllium
      seed husk at most time points. We conclude that collection site, adaptation of
      bacteria to the substrate to be fermented and duration of fermentation
      significantly influence the results of in vitro fermentation studies.

PMID- 7562079
TI  - Starvation and refeeding regulate glycogen synthase gene expression in rat liver
      at the posttranscriptional level.
AB  - Starvation and refeeding affect glycogen metabolism. The effects of starvation
      and refeeding on the level of glycogen synthase (GS) gene expression were
      examined in rat liver. Depletion of hepatic glycogen stores by 72 h of starvation
      (7% of control) was supercompensated by 24 h of refeeding a standard laboratory
      diet (247% of control). Upon further refeeding, glycogen concentration gradually
      returned to control levels after 120 h. After 72 h of starvation, GS activity and
      immunoreactive protein in the liver were 60-64% lower than in control rats with
      free access to food. After 72 h of refeeding, GS activity and immunoreactive
      protein returned to control values. No significant differences in GS mRNA levels
      were found between fed, starved and refed rats, as determined by Northern blot
      analysis and PCR quantification, indicating that the long-term regulation of GS
      gene expression in starvation and refeeding occurs via a posttranscriptional
      mechanism. The amount of GS mRNA associated with polyribosomes was 90% lower in
      starved than in fed rats. These data indicate that the efficiency of GS mRNA
      translation, rather than its abundance, decreases during starvation.

PMID- 7562081
TI  - The CD45RA+ (quiescent) cellular phenotype is overabundant relative to the CD45RA
      phenotype within the involuted splenic T cell population of weanling mice
      subjected to wasting protein-energy malnutrition.
AB  - The objective of this investigation was to determine whether an imbalance between
      naive- and memory-phenotype cells occurs within CD4+ and/or CD8+ splenic T cell
      subsets in models of protein-energy malnutrition (PEM) which produce wasting
      disease (loss of approximately 1.6% of body weight per day for 14 d) and profound
      depression in thymus-dependent immunity. Male and female weanling mice of
      disparate inbred strains, CBA/J and C57BL/6J, were allocated to the following
      groups: zero-time control (23 d old and 19 d old, respectively), ad libitum
      intake of a complete purified diet (19% crude protein, 17 kJ/g gross energy),
      restricted intake of the complete diet, and (C57BL/6J, only) ad libitum intake of
      an isocaloric low protein diet (0.6% crude protein). Surface expression of
      isoforms of CD45, a component of the T cell receptor complex, as well as of the
      accessory molecule, CD2, were assessed by flow cytometry of splenic mononuclear
      cell suspensions. Both major T cell subsets in the malnourished groups contained
      a significantly higher proportion of cells expressing the surface marker, CD45RA,
      than was found in the spleen cells of the control groups. CD45RA+ (naive
      phenotype) T cells represent the extreme of quiescence and stringent activation
      requirements among thymic lymphocytes. The results provide the first clear
      evidence of a T cell subset imbalance in PEM which is consistent with depression
      in acquired immunity and which occurs, apart from antigenic challenge, in a site
      wherein immune responses take place. The T cell receptor complex may emerge as a
      focal point of the depressive influence of PEM on the competence of thymic
      lymphocytes.

PMID- 7562082
TI  - Astaxanthin, a carotenoid without vitamin A activity, augments antibody responses
      in cultures including T-helper cell clones and suboptimal doses of antigen.
AB  - Astaxanthin, a carotenoid without vitamin A activity, enhances T-dependent
      antigen (Ag)-specific humoral immune responses. We examined carotenoid actions on
      T-helper (Th) cell activity in a direct manner with reconstitution experiments;
      spleen Th cells were replaced with Ag-specific Type 1 and Type 2 (Th1 and Th2) Th
      cell clones. The Ag for the Th1 and Th2 clones were pigeon cytochrome C and
      rabbit gamma-globulin, respectively. Astaxanthin and beta-carotene augmented the
      number of IgM antibody (Ab)-secreting cells when unprimed B cells were incubated
      with Th clones and stimulated with suboptimal doses of Ag specific for each Th
      clone. The number of IgG Ab-secreting cells were greater with use of in vivo
      primed B cells than with unprimed B cells in both Th clones. Astaxanthin but not
      beta-carotene augmented the number of IgG Ab-secreting cells when primed B cells
      and Th cell clones were stimulated with suboptimal doses of Ag specific for each
      Th clone. In the presence of optimal doses of Ag for each Th clone, neither
      carotenoid augmented the number of Ab-secreting cells. Astaxanthin and beta
      carotene may enhance the actions of both Th1 and Th2 cells for humoral immune
      responses with suboptimal Ag challenges; certain carotenoids may help maintain Ag
      mediated immune responses at optimal levels.

PMID- 7562083
TI  - Long-term supplementation of canthaxanthin does not inhibit gastric epithelial
      cell proliferation in Helicobacter mustelae-infected ferrets.
AB  - The effect of canthaxanthin (CX), a nonprovitamin A carotenoid, on gastric
      epithelial proliferation was studied in ferrets colonized with Helicobacter
      mustelae, which causes a chronic gastritis and an increased gastric epithelial
      cell proliferation. Seven spayed female ferrets were dosed by gavage with CX
      beadlets (50 mg/kg body wt, 5 d/wk) over 2 y, whereas seven control animals were
      given placebo beadlets. At the end of the 2-y-period, ferrets were killed, and
      gastric tissues were obtained from the antrum and body regions. A cell
      proliferating biomarker, proliferating cell nuclear antigen (PCNA), was assayed
      by immunohistochemistry. The PCNA positivity was measured by a computer-based
      image analysis system. Serum concentrations of carotenoids, retinoids and
      tocopherols were analyzed by HPLC. Serum antioxidant status was measured by the
      oxygen radical absorbance capacity (ORAC) assay. The PCNA positivity in both
      antrum and body regions was not significantly different between CX-fed ferrets
      and controls. Serum CX concentrations were significantly higher in CX-fed ferrets
      vs. controls (P < 0.001), whereas levels of other carotenoids, retinoids and
      tocopherols were not significantly different. The ORAC values were not
      significant different between groups. This study does not suggest inhibitory
      effects of CX on gastric epithelial cell proliferation in H. mustelae infected
      ferrets.

PMID- 7562085
TI  - Vitamin B-12 status of long-term adherents of a strict uncooked vegan diet
      ("living food diet") is compromised.
AB  - The present study examined the vitamin B-12 status in long-term adherents of a
      strict uncooked vegan diet called the "living food diet." The study was comprised
      of two parts. In the cross-sectional part, the data on serum vitamin B-12
      concentrations and dietary intakes in 21 (1 male, 20 females) long-term adherents
      (mean 5.2 y, range 0.7-14) of the "living food diet" were compared with those of
      21 omnivorous controls matched for sex, age, social status and residence. In the
      longitudinal part of the study, food consumption data were collected and blood
      samples were taken from nine "living food eaters" (1 male, 8 females) on two
      occasions 2 y apart. The cross-sectional study revealed significantly (P < 0.001,
      paired t test) lower serum vitamin B-12 concentrations in the vegans (mean 193
      pmol/L, range 35-408) compared with their matched omnivorous controls (311, 131
      482). In the vegan group, total vitamin B-12 intake correlated significantly (r =
      0.63, P < 0.01) with serum vitamin B-12 concentration. The vegans consuming Nori
      and/or Chlorella seaweeds (n = 16) had serum vitamin B-12 concentrations twice as
      high as those not using these seaweeds (n = 5) (mean 221 pmol/L, range 75-408,
      vs. 105, 35-252, P = 0.025). In the longitudinal study, six of nine vegans showed
      slow, but consistent deterioration of vitamin B-12 status over a 2-y observation
      period. On the basis of these results we conclude that some seaweeds consumed in
      large amounts can supply adequate amounts of bioavailable vitamin B-12.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562086
TI  - Estimates of the effect of feeding on whole-body protein degradation in women
      vary with the amino acid used as tracer.
AB  - We measured how feeding status affects the kinetics of multiple indispensable
      amino acids in four adult female subjects studied both in fed and fasted state.
      The subjects ingested one dose of uniformly 13C-labeled algae (Spirulina
      platensis). The isotopic enrichments (measured with negative chemical ionization
      gas chromatography-mass spectrometry) of the branched chain amino acids,
      phenylalanine, lysine and threonine were followed for 24 h in both the plasma and
      in VLDL-apolipoprotein B-100 (apoB-100). Fasting lowered body protein degradation
      when measured with the branched chain amino acids, increased it when measured
      with phenylalanine and had no statistically significant effect when determined
      from the kinetics of lysine and threonine. These apparent differences challenge
      the adequacy of current models of whole-body protein turnover. The ratio of the
      peak labeling of amino acids in plasma and apoB-100 was used as an estimate of
      the isotopic dilution in the hepatic pool. In contrast to our earlier
      observations during intravenous tracer amino acid administration, in the present
      study fasting lowered the ratio of the peak isotopic enrichments of apoB-100 and
      plasma amino acids. This supports our contention that feeding increases the use
      of hepatic portal amino acids for hepatic secretory protein synthesis.

PMID- 7562084
TI  - Arctic indigenous women consume greater than acceptable levels of
      organochlorines.
AB  - Exposure to polychlorinated biphenyls and organochlorine pesticides through
      traditional food resources was examined for Arctic Indigenous women living in two
      cultural and environmental areas of the Canadian Arctic--one community
      representing Baffin Island Inuit in eastern Arctic and two communities
      representing Sahtu Dene/Metis in western Arctic. Polychlorinated biphenyls,
      toxaphene, chlorobenzenes, hexachlorocyclohexanes,
      dichlorodiphenyltrichloroethane, chlordane-related compounds and dieldrin were
      determined in local food resources as normally prepared and eaten. Quantified
      dietary recalls taken seasonally reflected normal consumption patterns of these
      food resources by women in three age groups: 20-40 y, 41-60 y and > or = 61 y.
      There was wide variation of intake of all organochlorine contaminants in both
      areas and among age groups for the Sahtu. Fifty percent of the intake recalls
      collected from the Baffin Inuit exceeded the acceptable daily intake for
      chlordane-related compounds and toxaphene, and a substantial percentage of the
      intake records for dieldrin and polychlorinated biphenyls exceeded the acceptable
      or tolerable daily intake levels. Primary contributing foods to organochlorine
      contaminants intake for the Baffin Inuit were meat and blubber of ringed seal,
      blubber of walrus and mattak and blubber of narwal. Important foods contributing
      organochlorine contaminant to the Sahtu Dene/Metis were caribou, whitefish,
      inconnu, trout and duck. The superior nutritional benefits and potential health
      risks of traditional food items are reviewed, as are implications for monitoring
      organochlorine contaminant contents of food, clinical symptoms and food use.

PMID- 7562087
TI  - The arachidonic acid content of the Australian diet is lower than previously
      estimated.
AB  - Linoleic acid [18:2(n-6)] is the most abundant polyunsaturated fatty acid in the
      Western diet and is considered to be the primary source of tissue arachidonic
      acid [20:4(n-6)]. Dietary 20:4(n-6) may also contribute to tissue 20:4(n-6)
      levels in humans, but the extent of this contribution is unclear. We believe that
      literature estimates of 20:4(n-6) intake of 200-1000 mg/d are too high, possibly
      because of incorrect values in food composition tables where high amounts of
      20:4(n-6) are recorded in margarines, some vegetable products and animal fat. We
      assessed the 20:4(n-6) content of common Australian foods and found that the
      20:4(n-6) levels (on a 100-g edible basis), were 891 mg and 390 mg, respectively,
      for duck and chicken egg yolks, 294 mg for liver, 153 mg for kidney, 75 mg for
      skinless turkey, 56 mg for lean pork, 49 mg for lean lamb, 31 mg for chicken
      breast, 56 mg for chicken legs and 35 mg for lean beef. Eicosapentaenoic acid
      [20:5(n-3)] levels were < 10 mg/100 g in chicken meat, turkey meat, emu meat and
      chicken eggs, whereas the values for 20:5(n-3) for beef, lamb, liver, kidney and
      duck egg yolk ranged from 11 to 138 mg/100 g food. Applying our current 20:4(n-6)
      measurements to previously determined food intakes of Australian adults
      determined in an Australiawide survey in 1983, we estimated the mean 20:4(n-6)
      intake for Australian adult males to be 130 mg/d and females 96 mg/d. Whether
      such intakes of dietary 20:4(n-6) make an important contribution to tissue 20:4(n
      6) levels is uncertain.

PMID- 7562088
TI  - Lean and heavy women may not use energy from alcohol with equal efficiency.
AB  - To assess whether energy from alcohol is efficiently utilized to maintain body
      mass, we examined changes in energy intake of young women when they drank
      alcohol. The women ate controlled diets typical of the American diet with regard
      to macronutrients. Body weights were controlled to within 1 kg of entry level
      weights. The subjects were given alcohol (30 g/d) and no alcohol treatments for 3
      mo each in a crossover design. The treatments were isoenergetic; for the no
      alcohol treatment alcohol energy was replaced with energy from carbohydrate. The
      average change in energy intake associated with the alcohol treatment was
      negligible when all subjects were considered collectively. There was, however, a
      divergence in response between lean and heavy subjects. Fifteen women required,
      on average, an additional 886 +/- 147 (mean +/- SEM) kJ/d to maintain body weight
      during the alcohol treatment, and these women were leaner (body mass index 22.6
      +/- 0.8 kg/m2 vs. 25.2 +/- 1.0, P < 0.05) than the 22 women who required, on
      average, 559 +/- 139 fewer kJ/d when on the alcohol treatment. This study
      suggests that all subjects do not use energy from alcohol with equal efficiency.

PMID- 7562089
TI  - Carnitine palmitoyltransferase modulation of hepatic fatty acid metabolism and
      radio-HPLC evidence for low ketogenesis in neonatal pigs.
AB  - A neonatal piglet model was used to study hepatic fatty acid metabolism during
      the early postnatal period. Hepatocytes were isolated from pigs at birth or after
      24 h, in fed or unfed states (n = 4 pigs/group). Cells were incubated with 1
      mmol/L [1-(14)C]-octanoate (C8) or -palmitate (C16) in the presence or absence of
      1 mmol/L L-carnitine, carnitine plus tetradecylglycidic acid (TDGA; 10 mumol/L)
      or carnitine plus glucagon (0.5 microgram/L). Accumulation of radiolabel
      [nmol/(h. 10(6) cells)] in CO2 and acid-soluble products (ASP) was higher (3.5-
      and 4.5-fold, respectively) from C8 than from C16 (P < 0.0001). Glucagon,
      carnitine and TDGA had no effect on the oxidation of C8 (P > 0.1). Carnitine
      addition tended to increase C16 flux to ASP [from 5.3 to 7.6 nmol/(h. 10(6)
      cells); P < 0.1], whereas carnitine plus TDGA decreased flux (from 7.6 to 2.1; P
      < 0.001). Esterified products accounted for 70% of metabolized label in control
      C16 incubations; this was reduced to 62% by carnitine (P < 0.05) and increased to
      80% by the addition of carnitine plus TDGA (P < 0.0001). The 1-(14)C flux to CO2
      in cells from 24-h-old unfed piglets was 47% lower than from fed pigs (P < 0.01)
      but 28% higher than in pigs at birth. Radiolabel contained in ASP and total
      metabolized label were 48% lower from unfed pigs compared with the piglets at
      birth and 24-h-old fed pigs (P < 0.01) and were paralleled by changes in oxygen
      consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562090
TI  - In vivo threonine oxidation rate is dependent on threonine dietary supply in
      growing pigs fed low to adequate levels.
AB  - Threonine oxidation was examined in 12 growing pigs fed a well-balanced control
      diet or a threonine-deficient diet supplemented (Glu) or not (LT) with glutamic
      acid during constant infusion of L-[1-(13)C]-threonine, [1-(14)C]glycine and [1
      (14)C]alpha-ketobutyrate for 10 h. During these infusion, liver glycine
      enrichment was significantly lower than plasma enrichment. Moreover, the pancreas
      to plasma glycine enrichment ratio was higher than the liver to plasma ratio (70
      89%), showing that an important part of glycine de novo synthesis in pancreas
      occurred through the threonine dehydrogenase (TDG) pathway. These results imply
      that calculation of threonine oxidation into glycine should be made with the
      assumption of both hepatic and extrahepatic oxidation. Plateau values of plasma
      threonine, glycine and alpha-ketobutyrate enrichments and specific radio
      activities allowed estimations of threonine oxidation through the TDG and
      threonine dehydratase (TDH) pathways. Threonine oxidation into glycine was 12.16
      +/- 2.06, 2.89 +/- 0.61 and 2.13 +/- 0.44 mumol/(kg.h), respectively, in pigs fed
      the control, LT and Glu diets, and threonine oxidation into alpha-ketobutyrate
      was 1.80 +/- 0.31, 0.88 +/- 0.02 and 0.55 +/- 0.06 mumol/ (kg.h) for the control,
      LT and Glu groups, respectively. Total threonine oxidation rates were 75 and 81%
      lower in the LT and Glu groups, respectively, than in the control group. Liver
      TDG and TDH activity measured in vitro were not affected by either the level of
      dietary threonine supply the addition of glutamic acid. On the basis of plasma
      data, it may be concluded that the addition of glutamic acid to a threonine
      deficient diet had no significant effect on threonine oxidation but did reduce
      the rate of threonine release from protein breakdown. Oxidation appears to be
      related to plasma threonine concentration.

PMID- 7562094
TI  - Pantothenic acid uptake and metabolism by red blood cells of rats.
AB  - Red blood cells (RBC) of rats and humans contain pantothenic acid (PA)
      derivatives, generally referred to as bound PA, which were never characterized or
      quantitated. This study was undertaken to define those factors that determine the
      rates of uptake and efflux of PA, and possibly PA derivatives, in RBC. Uptake of
      PA by RBC was studied by incubating RBC with different concentrations of PA (0.34
      34.0 mumol/L), each containing [14C]PA (0.34 mumol/L) at 37 degrees C for 3-360
      min. The effects of Na+, energy and pH on the uptake of PA in RBC were determined
      in experiments varying media concentrations of Na+ (0-152 mmol/L), glucose (0 and
      10 mmol/L) or pH (7.2-7.6). The release of PA from RBC was studied by incubating
      RBC containing [14C]PA (0.10-10.4 nmol/10(7) RBC, final concentration) in fresh
      media at 37 degrees C for 10-240 min. Uptake and efflux of PA were found to be
      nonsaturable; uptake was not affected by Na+, energy or pH. Quantitative and
      qualitative determination of PA derivatives was by enzymatic hydrolysis of lysed
      RBC, followed by analysis of PA by RIA and paper chromatography. The RBC were
      found to contain PA, 4'-phosphopantothenic acid and pantetheine. We conclude that
      PA diffuses passively into and out of RBC and that RBC contain only PA, 4'
      phosphopantothenic acid, pantetheine and no CoA.

PMID- 7562091
TI  - para-acetamidobenzoylglutamate is a suitable indicator of folate catabolism in
      rats.
AB  - The amount of biologically active folate excreted in the urine corresponds to a
      small fraction of the recommended dietary allowance, suggesting that a large
      amount of folate is excreted as its catabolites. A strategy of assessing folate
      requirement by measuring the daily urinary levels of products of folate
      catabolism depends on the demonstration of an exclusive mechanism of breakdown as
      well as a suitable marker of the catabolic process. Rats were given [3H] and
      [14C]folic acid by gastric intubation daily for 10 d to simulate normal dietary
      intake of the vitamin. Total urine was collected throughout this period as well
      as for the following 10 d. Reverse-phase HPLC of the radiolabeled urinary
      products revealed the presence of a variety of intact folates as well as products
      of C9-N10 scission of the folate molecule, pteridines, para-aminobenzoylglutamate
      and para-acetamidobenzoylglutamate. We detected no other N10-containing
      catabolites, nor did we find the oxidized folate derivative '4 alpha-hydroxy-5
      methyltetrahydrofolate'. Of all the urinary folate metabolites, only para
      acetamidobenzoylglutmate persisted at high levels up to 10 d after radiolabel
      treatment was withdrawn. We conclude that folate catabolism occurs exclusively
      through C9-N10 cleavage and that measurement of urinary para
      acetamidobenzoylglutmate provides a suitable indicator of daily folate turnover.

PMID- 7562093
TI  - The transport of lysine across monolayers of human cultured intestinal cells
      (Caco-2) depends on Na(+)-dependent and Na(+)-independent mechanisms on different
      plasma membrane domains.
AB  - To characterize the mechanisms involved in the intestinal absorption of the
      essential amino acid L-lysine from the diet, the transepithelial transport of L
      lysine was studied in monolayers of cultured human intestinal cells (Caco-2)
      grown and differentiated on microporous membrane supports. L-lysine was
      transported mainly in the apical (AP) to basolateral (BL) direction and the BL to
      AP transport was approximately one order of magnitude lower at all concentrations
      tested. Non-linear regression analysis of the transport in the AP to BL and the
      BL to AP direction identified, in both cases, single saturable components with
      similar Km but different Vmax and a nonsaturable diffusional component. The AP to
      BL L-lysine transport was highly energy- and sodium-dependent and was unaffected
      by an unfavorable concentration gradient. Selective replacement of sodium ions in
      the AP or the BL compartment and determination of both AP to BL transport and the
      intracellular soluble lysine pool showed that uptake occurs via a sodium
      independent mechanism, not significantly influenced by membrane potential,
      whereas efflux is a sodium-dependent process. Competition experiments showed that
      L-lysine uptake is highly stereospecific and is shared by cationic and large
      neutral amino acids. This study demonstrates the presence of a sodium-dependent
      mechanism of lysine efflux across the BL membrane of intestinal cells, which may
      be essential for lysine transport into the blood circulation. Overall, these
      results support the use of the Caco-2 cell model for studies of intestinal
      nutrient transport.

PMID- 7562092
TI  - Splanchnic infusions of short chain fatty acids do not change insulin sensitivity
      of pigs.
AB  - Long-term ingestion of high fiber diets is associated with reduced glucose
      concentrations during fasting and improved glucose tolerance (KG) in humans. Our
      objective was to determine if the beneficial effects of fiber were attributable
      to increased production of short-chain fatty acid (SCFA) in the large intestine.
      Effects of SCFA on insulin sensitivity (SI), glucose effectiveness (SG), KG and
      baseline concentrations of glucose, insulin, glucagon and free fatty acids were
      examined in unfed 20-50 kg pigs (n = 6). Animals randomly received separate
      portal infusions (0.32 mL.min-1) of saline, acetic, propionic, and butyric acid
      solutions (0.01 mmol SCFA kg body weight-1.min-1) for 7-d periods. On d 7,
      somatostatin and tolbutamide modified frequently sampled intravenous glucose
      tolerance tests were performed. SI and SG were calculated using Bergman's Minimal
      Model. KG was determined by regression of log glucose curve versus time. SI, SG
      and KG values did not differ among the treatments (P > 0.05). Baseline
      concentrations of glucose, insulin, glucagon and free fatty acids were unaffected
      by infusion treatment (P > 0.05). Our results suggest that SCFA delivery is not
      directly responsible for improvements in glucose metabolism observed with long
      term ingestion of high fiber diets.

PMID- 7562095
TI  - A diet producing a low diabetes incidence modifies immune abnormalities in
      diabetes-prone BB rats.
AB  - The effect of feeding a diet that produces a high or low incidence of diabetes on
      immune abnormalities proposed to contribute to the pathogenesis of autoimmune
      mediated diabetes was investigated. Diabetes-prone (BBdp) and nondiabetes-prone
      (BBn) BB rats (21 d) were fed for 21 d a nonpurified (high incidence) or purified
      (low diabetes incidence) diet. Compared with BBn, immune cells from spleen and
      mesenteric lymph nodes of BBdp rats demonstrated higher rates of metabolite
      production from glucose and glutamine, higher splenic cytotoxicity (lysis of 51Cr
      labeled YAC-1 cells) and lower mitogen responses (3H thymidine uptake). Bypassing
      the membrane, using the mitogen phorbol myristate acetate + lonomycin, improved
      the BBdp mitogen response, suggesting a membrane defect. Immune cells from BBdp
      rats fed the purified, compared with the nonpurified, diet had lower rates of
      glutamine (spleen) and glucose (lymph nodes) metabolism and lower splenic
      cytotoxic activity. Although diet altered the proportion of T and B cells in
      lymph nodes of BBdp rats, it did not correct the abnormal lymphocyte distribution
      or effect mitogen responses. Feeding the purified, compared with nonpurified,
      diet to BBn rats altered energy metabolism by lymph node cells and resulted in
      lower splenic cytotoxic activity. Reduced splenic natural killer cell activity
      and decreased immune cell metabolism are unlikely the mechanism for the
      preventative effect of feeding a purified diet to BBdp rats but are indicative of
      reduced immune activity.

PMID- 7562096
TI  - Dietary fructooligosaccharide, xylooligosaccharide and gum arabic have variable
      effects on cecal and colonic microbiota and epithelial cell proliferation in mice
      and rats.
AB  - Two experiments were conducted to determine if supplementing soluble fiber
      (fructooligosaccharide, xylooligosaccharide or gum arabic) to a semi-elemental
      diet would beneficially change cecal and colonic microbiota populations and
      enhance epithelial cell proliferation. Experiments 1 and 2 used identical dietary
      regimens; mice and rats were given free access to a powdered semi-elemental diet.
      Animals were assigned to one of the four following treatment groups: control, no
      supplemental dietary fiber, fructooligosaccharide, xylooligosaccharide and gum
      arabic. Dietary fiber was supplied via drinking water at 30 g/L. In Experiment 1
      populations of Bifidobacteria and total anaerobic flora were enumerated from the
      contents of the cecum and colon of weanling mice. Consumption of
      fructooligosaccharide increased (P < 0.05) the concentrations of Bifidobacteria
      and the ratio of Bifidobacteria to total anaerobic flora. In Experiment 2 tissue
      from the cecum and distal colon of weanling rats was examined for morphological
      changes of the mucosa. Consumption of xylooligosaccharide increased (P < 0.05)
      cecal crypt depth and labeling index relative to the other three treatments.
      Consumption of gum arabic and the control diet increased (P < 0.01) cecal
      proliferation zone. Consumption of xylooligosaccharide and the control diet
      increased (P < 0.01) cecal cell density (number of cells in a vertical-half of
      the crypt). Distal colonic crypt depth was greatest (P < 0.05) in controls and
      rats fed fructooligosaccharide, intermediate in those fed gum arabic, and
      smallest in those fed xylooligosaccharide. These results suggest that
      fructooligosaccharide effectively stimulates growth of Bifidobacteria and
      xylooligosaccharide supports a modest enhancement of cecal epithelial cell
      proliferation.

PMID- 7562097
TI  - Distributions of carotenoids and alpha-tocopherol among lipoproteins do not
      change when human plasma is incubated in vitro.
AB  - Carotenoids and alpha-tocopherol are dietary, lipophilic antioxidants which may
      protect plasma lipoproteins from oxidation, a process believed to contribute to
      atherogenesis. In this study, the quantities and distributions of carotenoids,
      alpha-tocopherol and major lipids in the plasma and lipoproteins of seven
      normolipidemic humans were determined. Experiments were also conducted to
      determine if these antioxidants redistribute among lipoproteins when plasma is
      incubated in vitro. Virtually all of the total carotenoid in plasma associated
      with lipoproteins, primarily LDL [73 +/- 10% (mean +/- SD)], as did the more non
      polar individual carotenoids, beta-cryptoxanthin (68 +/- 9%); lycopene (79 +/-
      9%), and beta-carotene (72 +/- 12%), in patterns which closely resembled the
      distribution of total cholesterol. Xanthophyll, the most polar carotenoid
      examined, distributed equally between LDL (44 +/- 11%) and HDL (38 +/- 14%),
      whereas alpha-tocopherol associated with LDL (43 +/- 12%), HDL (26 +/- 10%), and
      VLDL (27 +/- 13%). These patterns closely resembled that of phospholipid.
      Approximately four carotenoid molecules associated with each VLDL and one with
      each LDL particle, whereas only 25 of every 1000 HDL particles contained
      carotenoid. Approximately 145 molecules of alpha-tocopherol associated with VLDL,
      12 with LDL, and one with each HDL particle. Unlike triglyceride and cholesteryl
      ester, known to transfer among lipoproteins through the action of cholesteryl
      ester transfer protein, net transfer of carotenoids and alpha-tocopherol among
      lipoproteins did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562098
TI  - Variations of blood pressures in lean Zucker rats fed low or high fat diets.
AB  - The purpose of this study was to determine whether lean (Fa/?) Zucker rats which
      exhibit greater metabolic efficiency in response to a high (48%) fat diet also
      exhibit hypertension.Twenty-nine lean (Fa/?) and eleven obese (fa/fa) Zucker rats
      were fed low (12% energy) and high (48% energy) fat diets. Food intake and weight
      change were recorded weekly to obtain an index of energy efficiency. After 6 wk,
      direct intra-arterial blood pressure was measured in conscious, unrestrained
      animals. Arterial blood was collected for analyses of plasma insulin and glucose.
      The high fat diet had no effect on blood pressure in obese rats, although obese
      animals fed both diets had significantly higher blood pressure than lean
      siblings. High fat feeding in lean rats unmasked a heterogeneity in blood
      pressure. Blood pressure in this group was significantly correlated with weight
      change, energy efficiency ratio and plasma glucose concentration. Lean rats fed
      the high fat diet with blood pressures above the group median exhibited
      significantly greater plasma insulin (P < 0.02) and glucose (P < 0.01)
      concentration and energy efficiency ratios (P < 0.01) than those with lower blood
      pressures. Thus, it appears that there were two groups of lean animals present,
      one of which was more phenotypically sensitive to high fat feeding than the
      other. This suggests a possible gene dosage effect of the fa allele in the Zucker
      rat model.

PMID- 7562099
TI  - Methionine deficiency decreases protein accretion and synthesis but not tRNA
      acylation in muscles of chicks.
AB  - The effect of supplementing a methionine-deficient, isolated soy protein diet
      (0.5% total sulfur amino acids) with 0.2% D,L-methionine (DL-MET) or a molar
      equivalent of D,L-2-hydroxy-4-(methylthio) butanoic acid (DL-HMB) was assessed in
      chicks over an 8-d feeding study. Chicks consumed DL-HMB diet ad libitum (HIGH)
      or were restricted to the level consumed ad libitum by chicks fed the basal diet.
      The DL-MET diet was fed at the same two levels as the DL-HMB diet. Supplementing
      with either methionine source resulted in significantly greater growth rate,
      efficiency of feed conversion, and accretion and synthesis of protein in the
      gastrocnemius and pectoralis muscles. These increases were greater for chicks
      consuming feed ad libitum as compared with feed-restricted chicks and were not
      affected by methionine source. Rate of muscle protein degradation appeared to
      increase with supplementation of either methionine source, but only when feed
      intake was permitted to increase. The relative in vivo conversion of DL-HMB vs. D
      MET to L-MET was similar in all groups as indicated by pool sizes of methionine,
      tRNA(met), and tRNA(cys), and rates of protein accretion and synthesis. These
      data demonstrate that dietary DL-HMB and DL-MET are used with similar efficacy to
      support skeletal muscle protein accretion and rates of protein synthesis when
      feed intake is equalized.

PMID- 7562100
TI  - Short-term moderate energy restriction does not affect indicators of oxidative
      stress and genotoxicity in humans.
AB  - Restriction of energy intake (ER), without malnutrition of essential nutrients,
      has repeatedly been demonstrated to increase longevity in rodents. In the
      antioxidant theory of aging the lack of balance between the generation of free
      radicals and free radical scavenging was thought to be a main causal agent, in
      the aging process. From this point of view the antiaging effect induced by ER
      might be due to the lower rate of free-radical production and related damage
      induced by a lower metabolic rate. The antiaging effects of ER might also occur
      in humans. This study explored the effects of a 10-week moderately energy
      restricted diet (80% of habitual) in 24 non-obese middle-aged men (16 ER
      subjects, 8 controls) on resting metabolic rate (RMR) and indicators of the
      primary antioxidant defense system, oxidative stress and genotoxicity. RMR
      decreased significantly in both groups, even when adjustments were made for the
      change in body composition. The increase in blood vitamin C concentration
      correlated with the increase in urinary 8-hydroxydeoxyguanosine (80HdG)
      excretion. The change in urinary 80HdG excretion also correlated with the change
      in RMR per kg fat-free mass. No differences between groups were found for changes
      in indicators of genotoxicity, erythrocyte catalase, glutathione peroxidase and
      superoxide dismutase activity and in plasma vitamin E, A or beta-carotene
      concentrations. We conclude that 10 weeks of moderate ER did not affect
      indicators of antioxidative capacity, oxidative stress and genotoxicity of
      humans. Since subjects were not in energy balance at the end of the study, no
      conclusions can be made with respect to long-term effects.

PMID- 7562101
TI  - Fish oils lower rat plasma and hepatic, but not immune cell alpha-tocopherol
      concentration.
AB  - These studies were designed to measure the impact of different fish oil sources
      of dietary (n-3) polyunsaturated fatty acid on the alpha-tocopherol content of
      rat immune cells. In the first experiment, rats were fed diets containing either
      lard, corn oil, menhaden fish oil or cod liver oil. In the second study, sardine
      fish oil replaced corn oil. Dietary fat source did not significantly influence
      body weights or the yield of immune cells in either study. In both studies,
      plasma and liver alpha-tocopherol concentrations were significantly lower in (n
      3) polyunsaturated fatty acid-fed rats than in rats fed lard. In the first study,
      immune cell alpha-tocopherol concentrations followed those observed in the plasma
      and liver. These concentrations closely paralleled the amount of RRR-alpha
      tocopheryl acetate added to diets and not the total vitamin E present, which was
      the same for all treatment groups. However, in the second study, alpha-tocopherol
      concentration of immune cells was not significantly different among rats fed
      lard, menhaden fish oil, and sardine fish oil. In that study both the amount and
      form of vitamin E were carefully balanced across dietary treatment groups. In
      conclusion, despite having similar amounts of (n-3) polyunsaturated fatty acids,
      two out of three fish oils tested did not lower immune cell alpha-tocopherol
      concentration even in the face of significantly reduced plasma and liver alpha
      tocopherol concentrations.

PMID- 7562102
TI  - Diets causing taurine depletion in cats substantially elevate postprandial plasma
      cholecystokinin concentration.
AB  - Excessive secretion of the intestinal hormone cholecystokinin (CCK) was
      postulated to cause diet-related taurine depletion in cats. To test this
      hypothesis, plasma CCK-like immunoreactivity (CCK-LI) was measured in cats given
      four diets, two purified and two canned, that contained similar concentrations of
      protein, fat, moisture and taurine but produced variable rates of taurine
      depletion. Plasma CCK-LI was measured by RIA with a tyrosine-sulfate specific, C
      terminal anti-serum, validated for use in cat plasma. As indicated by
      measurements of taurine in whole blood and urine, a purified diet containing
      casein maintained body taurine, whereas the same diet containing soybean protein
      and a commercial canned diet preserved either by freezing or cooking depleted
      body taurine. Preprandial and peak postprandial plasma CCK-LI in cats given the
      casein-containing diet were 10.6 +/- 1.4 and 27.6 +/- 4.8 pmol/L, respectively,
      approximately two- to tenfold greater than those reported in humans. Integrated
      postprandial plasma CCK-LI was less for cats given the casein diet than cats
      given both forms of the canned diet; it tended to be lower in cats given the
      casein diet than in cats given the soy protein diet. A negative linear
      correlation was observed between apparent nitrogen digestibilities of the diets
      and integrated plasma CCK-LI. The results indicated that diets that cause taurine
      depletion have lower protein digestibilities and cause greater endocrine
      secretion of CCK than diets that maintain body taurine status.

PMID- 7562103
TI  - Chronic intake of a marginally low copper diet impairs in vitro activities of
      lymphocytes and neutrophils from male rats despite minimal impact on conventional
      indicators of copper status.
AB  - We investigated the impact of chronic intake of a diet marginally low in Cu on
      traditional indicators of Cu status and in vitro activities of splenic
      mononuclear cells and neutrophils. Pregnant Sprague-Dawley rats were fed diets
      containing either 2.8 (LCu) or 6.7 [adequate (ACu)]mg Cu/kg from midgestation
      through lactation. Weaned male and female offspring were fed the same diets as
      their dams until 6 months of age. Dietary Cu level did not alter growth, heart
      weight, the concentrations of Cu or the activities of cuproenzymes in serum and
      most tissues. In contrast, splenic mononuclear cells (MNC) from males, but not
      females, fed the LCu diet were less responsive to in vitro mitogenic activation
      and generated less interleukin-2 bioactivity than cultures prepared from males
      fed the ACu diet. Repletion with the ACu diet for 2 wk restored in vitro
      activities of splenic MNC to control levels. The phorbol myristate acetate
      induced generation of superoxide anion by elicited neutrophils from male rodents
      fed the LCu diet was only 60% that of cells from the ACu diet group. Brain Cu in
      adult rats fed LCu diet was irreversibly decreased compared with those fed ACu
      diet. These data show that the in vitro activities of T lymphocytes and
      neutrophils isolated from adult male rats chronically fed a diet marginally low
      in Cu were significantly suppressed without marked alterations in the traditional
      indicators of Cu status.

PMID- 7562106
TI  - Coupling of zinc dose to frequency in a regularly recurrent pattern shows a
      limited capacity of excessive dietary zinc to compensate for a previously
      deficient intake.
AB  - The impact of feeding a proportional dose of zinc in a regularly recurrent
      pattern (idiorrhythmic feeding) on body growth of weanling rats was studied to
      assess the extent to which an intake exceeding the requirement could compensate
      for a previously deficient intake. The idiorrhythmic regimen (1) was designed so
      that the overall dose-time equivalent (modulo; Mx) was kept constant over a
      selected period of time (epoch; E), whereas the actual dose and frequency varied
      regularly according to a predetermined pattern; that is, I = dnth(Mx)/dnth, where
      Mx and dnth are the selected dose-time equivalent and the sequential number of
      zinc-dosing days, respectively. For example, 3 mg Zn.kg-1 diet fed every day (I =
      3/1) and 24 mg Zn.kg-1 diet fed 1 d in an 8-d period (7 d of feeding a zinc
      deficient diet) (I = 24/8) are dose-time equivalents because they both provide 72
      mg Zn.kg-1 over a 24-d E. Modulos of M3, M6, M12 and M24 were used, which
      provided 3, 6, 12 and 24 mg Zn.kg-1.d-1 dose-time equivalents during a 24-d E.
      Each modulo had seven analogous idiorrhythms: I = Mx/1, 2Mx/2, 3Mx/3, 4Mx/4,
      5Mx/5, 6Mx/6 and 8Mx/8; for example, with 8 Mx/8, 24, 48, 96 or 192 mg Zn.kg-1
      diet was fed every 8th d; on the other 7 d a diet without a zinc supplement was
      fed for M3, M6, M12 and M24, respectively. Zinc dose-rate idiorrhythm generated a
      complex, gestalt-like, biphasic growth response pattern where an intake of
      dietary zinc exceeding requirements had either no effect (M3 or average of 3 mg
      kg-1 diet) or fully compensated for only 1 (M6 and M12 or average of 6 and 12 mg
      Zn.kg-1 diet) or 2 (M24 or average of 24 mg Zn.kg-1 diet) d.

PMID- 7562105
TI  - Calcium metabolism and requirements of chickens are affected by growth.
AB  - The interaction between growth and calcium homeostasis was studied by comparing
      the responses of (a) fast-growing broiler chickens (Cobb) and slow-growing
      Leghorns, and (b) fast-growing chickens (Cobb) fed either high energy (12.13
      kJ/g) or low energy (9.2 kJ/g) diets, to dietary calcium concentration ranging
      between 4 and 20 g/kg). Plasma calcium increased as dietary calcium increased,
      reaching an apparent plateau between 0.8 and 1.5% dietary calcium, regardless of
      basal growth rate. Dietary calcium levels of 1.5% and higher induced
      hypercalcemia and hypophosphatemia in fast- but not in slow-growing chickens.
      Weight gain was unaffected by dietary calcium in the slow-growing Leghorns, but
      followed a bell-shaped response pattern in the fast-growing Cobb chickens. Growth
      inhibition by feeding of low energy diets changed the response pattern from a
      quadratic form to that of an increase towards a plateau. The response of bone ash
      to dietary calcium was characterized as quadratic in fast-growing chicks,
      changing to a pattern of increase towards a plateau in slow-growing chicks.
      Intestinal calbindin was suppressed by dietary calcium and was higher in the fast
      growing than in the slow-growing chicks. An increase in dietary phosphorus
      resulted in a shift in the response curves of weight gain and bone ash and an
      increase in the calcium requirements. The results indicate that the response of
      chicks to dietary calcium and calcium requirements is markedly modified by growth
      rate.

PMID- 7562104
TI  - Rats treated with somatotropin select diets higher in protein.
AB  - It was previously shown that somatotropin (STH) increases growth rate, improves
      food efficiency and stimulates protein accretion. In rats, STH also increases
      food intake. This study examined the effect of exogenous STH on rats' selection
      of diets varying in protein content. It was hypothesized that the increase in
      food intake in response to STH is driven by an increased protein requirement.
      Rats were allowed to select between two diets varying in casein (5 and 30%) or
      given a diet of a single casein level (20%). In each diet group, rats were
      treated with 0 or 4 mg of porcine STH/d. Rats treated with STH showed greater
      food intake (20%) and protein accretion (125%), regardless of diet. However, the
      greater food intake in rats allowed to select was due to greater consumption of
      the high protein diet. Diet selecting, STH-treated rats consumed 75% more of the
      30% casein diet than did the saline-treated controls, while consuming a similar
      amount of 5% casein diet. Total protein intake (g/d) was 22 and 53% greater in
      rats injected with STH consuming the 20% casein diet and selection diets,
      respectively. The results indicate that rats injected with somatotropin select a
      diet greater in protein when compared with those not receiving somatotropin. It
      is suggested that the STH-induced increase in protein accretion results in a
      greater demand for essential amino acids. The mechanism whereby animals are able
      to monitor this greater need is not clear.

PMID- 7562107
TI  - Moderate copper deprivation during gestation and lactation affects dentate gyrus
      and hippocampal maturation in immature male rats.
AB  - The hippocampal formation (HF) is involved in higher brain functions including
      learning and declarative memory. The possibility that dietary copper has a role
      in the morphological development, and therefore the function of the HF, has
      received little attention. A rat model of tiered copper deficiency, initiated
      during gestation, was employed to determine the susceptibility of the HF, regions
      of which develop postnatally, to copper deficiency. At postnatal 23, pups whose
      dams had received either 1.8 or 1.4 mg Cu/kg diet during both gestation and
      lactation, compared with offspring of a group that had received 4.3 mg Cu/kg diet
      during both periods had, significantly more cell nuclei in the infrapyrimidal arm
      of the dentate gyrus. Offspring of rats fed 1.4 mg Cu/kg diet, but not those fed
      1.8 mg/kg, compared with those fed 4.3 mg/kg, exhibited smaller, shorter, and
      narrower cell nuclei in the infrapyrimidal and suprapyrimidal arms of the dentate
      gyrus and smaller cell nuclei in region CA3c of the hippocampus. A fourth group
      (gestation, 1.8 mg Cu/kg diet; lactation, 0.9 mg Cu/kg diet) exhibited
      alterations less marked than those exhibited by the group fed 1.4 mg Cu/kg diet.
      All alterations in the groups fed low copper diets were consistent with slowed
      cell nuclear maturation. The findings indicate that copper is required for
      maturation of the dentate gyrus and hippocampus. Also, copper supplied at or
      below 1.8 mg/kg is insufficient for morphological maturation of the dentate gyrus
      and hippocampus. Because the HF is important for higher brain functions, further
      research is needed to determine whether the copper deficiency-induced alterations
      in dentate gyrus and hippocampus development are transient or permanent.

PMID- 7562109
TI  - Controlled dietary folate affects folate status in nonpregnant women.
AB  - In a study designed to estimate the requirement for dietary folate in nonpregnant
      women, 17 women (21-27 y) consumed 200, 300, or 400 micrograms/d of total folate
      for 70 d which was provided by low folate conventional foods (30 micrograms) plus
      supplemental folic acid. Group means for initial serum and erythrocyte folate and
      plasma homocysteine concentrations were not significantly different. Serum and
      erythrocyte folate decreased relative to the initial value in the 200
      micrograms/d group (43.4 +/- 12.1%, 13.6 +/- 16.6%, respectively; mean +/- SD),
      in contrast to an increase in the 400 micrograms/d group (16.8 +/- 52.0%, 10.2 +/
      18.5%, respectively). The final serum folate in the 200 and 300 micrograms/d
      groups (6.4 +/- 0.8 nmol/L, 7.3 +/- 1.1 nmol/L, respectively) was significantly
      lower than that of the 400 micrograms/d group (14.3 +/- 2.0 nmol/L), with
      evidence in the 200 micrograms/d and 300 micrograms/d groups of low ( < 6.8
      nmol/L) serum folate concentrations. Differences in final erythrocyte folate did
      not reach statistical significance, although low values ( < 362 nmol/L) were
      frequent in subjects with 200 micrograms/d intake. In the 200 micrograms/d group,
      plasma homocysteine was negatively correlated with serum and erythrocyte folate,
      and final mean plasma homocysteine (12.6 +/- 1.7 mumol/L) was significantly
      higher than that of the 300 or 400 micrograms/d groups. Elevated plasma
      homocysteine levels ( > 16 mumol/L) were observed in the 200 micrograms/d group
      only.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562108
TI  - Seasonal vitamin A depletion in grazing horses is assessed better by the relative
      dose response test than by serum retinol concentration.
AB  - Vitamin A influences growth and reproduction in horses. A retinol dose response
      (RDR) test for retinol has been shown to be better than serum retinol
      concentration for assessing vitamin A status in other species, so we have
      compared these two methods in the horse. Forty-five Thoroughbred broodmares were
      assigned randomly to three groups fed pasture and hay (PH), pasture, hay and
      vitamin A-free concentrate (PHC), or hay and concentrate (HC) in early summer
      (May 1991). Mares in pasture groups produced 23 foals (March through June) that
      had access to their dam's diets and were also studied. In the mares, significant
      vitamin A depletion developed in 2 mo in the nonpasture group (HC) and in 8 mo in
      the two pasture groups (PH and PHC) according to the RDR test, and in all three
      groups at 8 mo as shown by a decrease in serum retinol concentration. In the
      weanlings (PH and PHC only), no differences between groups were found for serum
      retinol, but the RDR was significantly higher in the PH group, which had suffered
      a respiratory infection, than in the PHC group. These findings indicated that
      vitamin A depletion was detected more readily by the RDR test than by serum
      retinol concentration, that consumption of pasture delayed depletion in the late
      fall, and that infection was associated with lower vitamin A status.

PMID- 7562110
TI  - The mobilization and tissue distribution of beta-carotene in the rat by the
      venous injection method.
AB  - Now it is known that beta-carotene (beta-carotene) has other important biological
      functions in addition to the role of vitamin A precursor. The various
      epidemiological studies suggested that high beta-carotene intake might reduce the
      incidence of the cancer risk. Although several studies are under way to find
      biological evidence for the epidemiological results, the mechanism of action of
      beta-carotene is still unknown. As the first step to elucidate the biological
      functions of beta-carotene, we investigated the mobilization and the distribution
      of all-trans-beta-carotene in the rat. Because it was reported that the rat did
      not absorb the intact form of beta-carotene, we injected a beta-carotene
      suspension intravenously (dose; 2.0 mg/rat). After injection, a high amount of
      beta-carotene (about 1.5 mg-2.0 mg) accumulated in the lung very rapidly (within
      5 min). By this method, the time-dependent mobilization and distribution of beta
      carotene in the rat was as follows: all-trans-beta-carotene was accumulated in
      the lung then moved to the liver, was distributed in adipose tissues (after 1
      week), pancreas (after 2 weeks), and muscle tissue or testis (after 3 weeks).

PMID- 7562111
TI  - Poor fermentability of "mekabu" (sporophyll of Undaria pinnatifida) alginic acid
      in batch culture using pig cecal bacteria.
AB  - Sodium alginate, mannuronic acid-rich and guluronic acid-rich fractions were
      prepared from "Mekabu" (sporophyll of Undaria pinnatifida). The production of
      short-chain fatty acids such as acetic, propionic and n-butyric acids from these
      fractions in mini-scale batch culture using pig cecal bacteria was studied, and
      the gas released from the culture was monitored. The volume of released gas
      corrected for blank value decreased in the order: glucose (a reference substrate)
      > guluronic acid-rich fraction > sodium alginate = mannuronic acid-rich fraction.
      The amounts of short-chain fatty acids produced from three fractions of alginic
      acid were smaller than that of glucose. These results suggested that alginic acid
      was poorly fermentable for hindgut bacteria and that its contribution to the host
      energy pool via microbial metabolism is small.

PMID- 7562113
TI  - Effect of cysteine on expression of cystathionine beta-synthase in the rat liver.
AB  - Hepatic cystathionine beta-synthase activity is decreased by the addition of
      cysteine to the diet. This effect of cysteine was slightly greater in diets
      containing 0.25% methionine than in those containing 1% methionine, and was
      reduced during aging. Similar changes were observed in the level of the mRNA of
      this enzyme, although the changes in the transcript levels were slightly greater
      than the changes in enzyme activity. Thus, we conclude that the addition of
      cysteine to a methionine-containing diet causes a decrease in cystathionine beta
      synthase activity mainly by diminishing its mRNA level.

PMID- 7562114
TI  - Polyunsaturated fatty acid-mediated suppression of insulin-dependent gene
      expression of lipogenic enzymes in rat liver.
AB  - The effects of dietary polyunsaturated fat on insulin-dependent gene expression
      of lipogenic enzymes and a possible mechanism for PUFA-mediated suppression of
      the gene expression have been investigated in rat livers. When diabetic rats were
      injected with insulin, the insulin dose-dependent induction of lipogenic enzyme
      mRNAs were markedly reduced with increasing dietary corn oil. On the other hand,
      the PUFA-mediated suppression of the mRNA concentrations was partially restored
      by treatment with pioglitazone, a candidate for increasing insulin receptor
      phosphorylation. Moreover, insulin binding to receptors of liver, receptor
      autophosphorylation, and kinase activity toward exogenous substrate were lower in
      the corn oil diet group than in the hydrogenated fat group. The PUFA-mediated
      suppression of insulin binding was somewhat restored by pioglitazone, and the
      suppression of insulin receptor phosphorylation was significantly restored. It is
      suggested that the PUFA-mediated suppression of insulin-dependent gene expression
      of lipogenic enzymes can be ascribed to a decrease in insulin receptor binding
      primarily and also to receptor phosphorylation. Thus, PUFA appears to suppress
      the lipogenic enzyme gene expression stimulated by insulin.

PMID- 7562112
TI  - Antihypercholesterolemic effect of undigested fraction of soybean protein in
      young female volunteers.
AB  - The significant antihypercholesterolemic effect of the undigested high molecular
      fraction (HMF) of soybean protein is known in rats, but such an effect has not
      been shown in humans. The present two experiments were designed to elucidate it
      in humans. Subjects were female university students who had relatively high serum
      cholesterol levels for their age. In Experiment 1, subjects took 8% of their
      total energy from casein, soybean protein isolate (SPI), or HMF daily for 14
      days. Five basic menus and snacks were cycled. Energy intakes and daily
      activities were kept constant and body weight was maintained. The HMF group
      showed decreased low-density lipoprotein cholesterol (LDL-C) as compared to other
      groups. In Experiment 2, subjects took 4% of total energy from casein or HMF
      daily for a menstruation period. Five basic menus and snacks which contained two
      egg yolks (about 500 mg cholesterol) were cycled. Energy intakes and daily
      activities were kept constant and body weight was maintained. A decrease in LDL-C
      and an increase in high-density lipoprotein cholesterol (HDL-C) were observed in
      the HMF group as compared to the casein group. Fecal acidic steroid excretion was
      greater in the HMF group than in the casein group (p < 0.05). The results
      confirmed that HMF increases fecal steroid excretion and reduces serum
      cholesterol levels in humans.

PMID- 7562115
TI  - Effects of sesamin on the fatty acid composition of the liver of rats fed N-6 and
      N-3 fatty acid-rich diet.
AB  - Sesamin is known as a specific inhibitor of delta 5-desaturation, the conversion
      from dihomo-gamma-linolenic acid (20:3(n=6)) to arachidonic acid (20:4(n-6)). In
      the previous paper, we reported that sesamin inhibited delta 5-desaturation of n
      6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20:4(n-3)
      to 20:5(n-3). Then, we studied the effects of sesamin on delta 5-desaturation of
      n-6 and n-3 fatty acids in vivo. Rats were fed two types of diets containing
      sesamin (0.5% w/w) for 4 weeks as follows: in experiment 1 (Exp. 1) gamma
      linolenic acid-rich diet and in experiment 2 (Exp. 2) alpha-linolenic acid-rich
      diet. The fatty acid composition of liver lipids was compared to those of control
      groups without sesamin. In both Exps. 1 and 2, sesamin increased the liver weight
      and phospholipid contents in liver. In Exp. 2, sesamin increased n-6 fatty acids
      and decreased n-3 fatty acids even though the diet was rich in n-3 fatty acids.
      Sesamin enhanced the composition ratio of 20:3(n-6) in both Exps. 1 and 2.
      Decrease of delta 5-desaturation index of n-6 fatty acid, the ratio of 20:4(n
      6)/20:3(n-6), by the administration of sesamin suggested that sesamin inhibited
      the delta 5-desaturation of n-6 fatty acids in the liver. On the contrary, the
      delta 5-desaturation index of n-3 fatty acids, the ratio of 20:5(n-3) to 18:3(n
      3), was increased by sesamin administration in the liver of rats fed alpha
      linolenic acid-rich diet (Exp. 2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562117
TI  - The concentration of epidermal growth factor in Japanese mother's milk.
AB  - The concentration of epidermal growth factor (EGF) in human milk was measured by
      radioreceptor assay (RRA). Human milk samples collected from healthy Japanese
      mothers who delivered at full term were divided into 30 groups according to
      differences in the duration of lactation, seasons of the year and place of
      residence. Human milk collected from 3 to 5 days after delivery in winter and
      summer contained 15.03 micrograms/100 ml and 15.46 micrograms/100 ml of EGF,
      respectively. The concentrations decreased rapidly to 8.04 micrograms/100 ml and
      8.12 micrograms/100 ml in milk from 31 to 60 days, and to 5.10 micrograms/100 ml
      and 5.44 micrograms/100 ml in milk from 241 to 481 days. Seasonal and regional
      differences in EGF concentration were observed to some extent, but no clear
      tendency could be defined. These results suggest that EGF is an essential and
      fundamental factor for the growth of infants in the very early stages after
      delivery, because it was high only at the beginning of lactation and then it
      decreased.

PMID- 7562116
TI  - Effects of dietary protein on the induction of DNA synthesis and expression of
      growth-related genes in liver and kidney of growing rats.
AB  - To investigate molecular mechanisms of growth control by protein nutrition, we
      examined whether nutritive quality of protein affects the induction of DNA
      synthesis in liver and kidney of growing rats in relation to expression of growth
      related genes such as c-myc, c-fos, c-Ha-ras, and ornithine decarboxylase (ODC).
      Rats were adapted to 2-h meal feeding schedule at first with laboratory chow for
      10 days and then with a protein-free diet for 3 days prior to experiments. When
      protein-free diet was fed to the rats, the levels of c-myc, ODC and c-Ha-ras
      mRNAs increased in the liver within 2 days. However, substantial changes in the
      levels of those mRNAs were not observed in the kidney. The level of c-fos mRNA in
      these tissues was too low to detect by our method. Feeding of casein diet to rats
      that had been maintained on protein-free diet for 3 days caused a rapid decrease
      in the level of c-myc mRNA and induced DNA synthesis in the liver. On the other
      hand, zein diet, which lacks tryptophan and lysine, did not lower the c-myc mRNA
      level nor induced DNA synthesis in the liver. However, if zein diet was
      supplemented with tryptophan and lysine, a decrease in c-myc mRNA level and an
      induction of DNA synthesis were observed. The levels of ODC and c-Ha-ras mRNAs
      were not changed by feeding of casein or zein diet. Neither casein nor zein
      induced DNA synthesis and changed the levels of the mRNA in the kidney. The
      amount of food intake during the 2-h feeding period was not different among the
      diets. These results suggest that the liver cells are arrested in G1 phase during
      the feeding of protein-free diet and good quality of protein is required to
      progress the cell cycle to enter S phase.

PMID- 7562118
TI  - Adaptive response of apolipoprotein A-I and A-IV mRNA in residual ileum after
      massive small bowel resection in rats.
AB  - The response of apolipoproteins, which are synthesized mainly in the small
      intestine, after small bowel resection has not been documented. In this study, we
      investigated the effect of small bowel resection on the expression of
      apolipoprotein mRNA in the residual ileum in rats. Wistar rats underwent either
      an 85% jejunoileal resection or a sham-operation. Plasma concentrations of total
      and HDL-cholesterol, apolipoprotein A-I and A-IV were measured on days 0, 3, 6,
      9, 12, and 16 (surgery on day 1). The abundances of apolipoprotein mRNA in the
      residual ileum and liver on day 16 were determined. Plasma levels of total and
      HDL-cholesterol and apolipoprotein A-I and A-IV in resected rats were
      significantly lower than in sham-operated rats on days 3 and 6. Resected rats
      showed a significant increase in ileal apolipoprotein A-I (1.2-fold) and A-IV
      (3.2-fold) mRNA compared with sham-operated animals. Hepatic apolipoprotein mRNA
      were the same between two groups. These data suggest that the residual ileum
      adapts to jejunoileal resection by selective increases in apolipoprotein A-I and
      A-IV expression at a pretranslational stage. The recoveries of apolipoprotein A-I
      and A-IV in plasma appear to depend, at least in part, on the increased
      expression of these apolipoproteins in the residual ileum.

PMID- 7562119
TI  - In situ intestinal absorption of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid in
      guinea pigs.
AB  - The intestinal absorption efficacy of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid
      (AA-2G), which has been recently synthesized and characterized as a stable
      ascorbate (AsA), was determined in guinea pigs by the perfusion technique.
      Perfusion of AA-2G in isotonic phosphate buffer to the small intestine resulted
      in a decrease of AA-2G accompanied by an increase of AsA in the perfusate. The
      results showed that intact AA-2G was not detected in the plasma of the portal
      vein of guinea pigs at 2 h after perfusion. The disappearance of AA-2G from
      perfusate was completely inhibited by the addition of castanospermine, a specific
      alpha-glucosidase inhibitor, or by carbohydrates such as maltose. These results
      indicate that ascorbic acid released from AA-2G by alpha-glucosidase on the brush
      border membrane is effectively taken up across the intestinal ascorbate transport
      channels, into a serosal site, whereas AA-2G permeation was poor via the passive
      transport system.

PMID- 7562120
TI  - Adherence to screening mammography recommendations in a university general
      medicine clinic.
AB  - OBJECTIVE: To determine factors predicting adherence to a health care provider's
      screening mammography recommendation in a general internal medicine practice.
      DESIGN: Prospective observational study. SETTING: An urban academic general
      internal medicine practice. PATIENTS: Three hundred forty-nine asymptomatic
      women, aged 50 years and older, without prior history of breast cancer, who
      received a health care provider's recommendation for screening mammography.
      MEASUREMENT: Independent variables were: patient age, race, insurance type,
      educational level, and duration of affiliation with the practice; visit type; and
      health care provider gender and level of training. Dependent variables were
      acceptance of the recommendation and adherence, defined as undergoing mammography
      within three months of the recommendation. RESULTS: Overall, 193 (55%) of the
      women underwent the recommended mammography. Two hundred ninety-eight (85%)
      initially agreed to the recommendation, and of these, 190 (64%) completed
      mammography within three months. By univariate analysis, acceptance of the
      recommendation decreased significantly with increasing age (p < 0.01), and by
      race (African-Americans 89% vs whites 82%, p = 0.05). Only age remained
      independently predictive of acceptance in a multiple variable analysis. Among
      women who accepted the recommendation, adherence varied significantly according
      to race (white 70% vs nonwhite 59%, p = 0.05), insurance type [Medicare as only
      insurance 45%, Medicaid 66%, non-health maintenance organization (non-HMO)
      private 62%, HMO 73%, p = 0.03], and health care provider training (attending
      physicians 73%, residents 58%, nurse practitioners 47%, p = 0.02). In a logistic
      regression analysis, insurance type and health care provider training remained
      independently predictive of adherence. CONCLUSION: Acceptance of screening
      mammography recommendations decreases with age. Among the women who agreed to the
      recommendation for screening mammography, insurance type and health care provider
      level of training best predicted adherence.

PMID- 7562121
TI  - In-hospital complications among survivors of admission for congestive heart
      failure, chronic obstructive pulmonary disease, or diabetes mellitus.
AB  - OBJECTIVE: To determine the frequency of hospital complications among survivors
      of inpatient treatment for congestive heart failure (CHF), chronic obstructive
      pulmonary disease (COPD), or diabetes mellitus (DM). DESIGN: Retrospective cohort
      study. SETTING: Nine Veterans Affairs hospitals in the southern United States.
      PATIENTS: 1,837 men veterans discharged alive following hospitalization for CHF,
      COPD, or DM between January 1987 and December 1989. This patient population
      represents a subset of cases gathered to study the process of care in the
      hospital and subsequent early readmission; thus, veterans who died in the
      hospital were not included. MEASUREMENTS: Medical record review to record the
      occurrence of any of 30 in-hospital complications such as cardiac arrest,
      nosocomial infections, or delirium (overall agreement between two reviewers =
      84%, kappa = 0.37). RESULTS: Complications occurred in 15.7% of the CHF cases,
      13.1% of the COPD cases, and 14.8% of the DM cases. Hypoglycemic reactions were
      the most frequent individual adverse events in the CHF and DM cases (3.6% and
      11.4% of the cases, respectively), and theophylline toxicity was most frequent
      among the COPD cases (4.9%). Patient age, the presence of comorbid diseases, and
      the Acute Physiology Score (APS) of APACHE II were associated with complication
      occurrence. For each disease, the patients who had a complication had
      significantly longer mean hospital stays than did the patients who did not have
      complications (14.6 to 14.9 days vs 7.2 to 8.2 days, p < 0.01). CONCLUSIONS:
      Complications are frequent among patients discharged alive with CHF, COPD, or DM.
      The patients who experienced complications were more ill on admission and had
      longer hospital stays.

PMID- 7562122
TI  - Improving residents' confidence in using psychosocial skills.
AB  - OBJECTIVE: To evaluate an intensive training program's effects on residents'
      confidence in their ability in, anticipation of positive outcomes from, and
      personal commitment to psychosocial behaviors. DESIGN: Controlled randomized
      study. SETTING: A university- and community-based primary care residency training
      program. PARTICIPANTS: 26 first-year residents in internal medicine and family
      practice. INTERVENTION: The residents were randomly assigned to a control group
      or to one-month intensive training centered on psychosocial skills needed in
      primary care. MEASUREMENTS: Questionnaires measuring knowledge of psychosocial
      medicine, and self-confidence in, anticipation of positive outcomes from, and
      personal commitment to five skill areas: psychological sensitivity, emotional
      sensitivity, management of somatization, and directive and nondirective
      facilitation of patient communication. RESULTS: The trained residents expressed
      higher self-confidence in all five areas of psychosocial skill (p < 0.03 for all
      tests), anticipated more positive outcomes for emotional sensitivity (p = 0.05),
      managing somatization (p = 0.03), and nondirectively facilitating patient
      communication (p = 0.02), and were more strongly committed to being emotionally
      sensitive (p = 0.055) and managing somatization (p = 0.056), compared with the
      untrained residents. The trained residents also evidenced more knowledge of
      psychosocial medicine than did the untrained residents (p < 0.001). CONCLUSIONS:
      Intensive psychosocial training improves residents' self-confidence in their
      ability regarding key psychosocial behaviors and increases their knowledge of
      psychosocial medicine. Training also increases anticipation of positive outcomes
      from and personal commitment to some, but not all, psychosocial skills.

PMID- 7562123
TI  - A cost-effectiveness model of thrombolytic therapy for acute myocardial
      infarction.
AB  - OBJECTIVE: To assess the short- and long-term costs and clinical and quality of
      life outcomes with the use of streptokinase (SK) vs tissue plasminogen activator
      (tPA) for acute myocardial infarction (MI). DESIGN: A decision analysis model.
      PATIENTS: Patients with acute MI who were candidates for thrombolytic therapy and
      who presented within six hours of symptom onset. MEASUREMENTS: 30-day and one
      year mortality, impacts of disabling and nondisabling stroke, reinfarction,
      hemorrhage, hypotension, anaphylaxis, and long-term medical costs. RESULTS: Using
      30-day mortality data from the Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, the baseline
      analysis yielded an incremental cost-effectiveness for tPA of $30,300 per
      additional quality-adjusted life year (QALY) gained, compared with SK. Using one
      year mortality data from the GUSTO trial, the analysis yielded an incremental
      cost-effectiveness for tPA of $27,400 per additional QALY, compared with SK. The
      incremental cost-effectiveness of tPA over SK was sensitive to the difference in
      mortality seen with the two agents, exceeding $100,000 per QALY, for a relative
      survival advantage of approximately one-third that seen in the GUSTO trial. The
      incremental cost per QALY of tPA remained under $60,000 if the survival benefit
      was half that seen in the GUSTO trial. The cost-effectiveness of tPA declined
      with a shorter projected life expectancy following MI and for inferior (vs
      anterior) wall infarction. The analysis was modestly sensitive to the costs of
      the thrombolytic agents. CONCLUSIONS: In spite of its higher cost relative to SK,
      tPA is a cost-effective therapy for MI under a wide range of assumptions
      regarding clinical outcomes and costs.

PMID- 7562124
TI  - Internal medicine update: seven important advances in medical diagnosis and
      management for the general internist.

PMID- 7562125
TI  - Inadequacy of intravenous heparin therapy in the initial management of venous
      thromboembolism.
AB  - To determine the adequacy of initial anticoagulation by intravenous heparin for
      patients who have deep venous thrombosis (DVT), and the factors that influence
      delayed anticoagulation, independent, duplicate chart review of 63 consecutive
      patients who had venography-proven DVT was conducted. Adequate heparinization
      (AH) was defined as an activated partial thromboplastin time (PTT) of more than
      1.5 times the normal laboratory control. The proportions of patients achieving AH
      within 24 hours and 48 hours of initial heparin bolus were 46% and 62%,
      respectively. Patients who weighed more were less likely to achieve AH (p <
      0.05), while patients receiving care from the thromboembolism service were more
      likely to achieve AH (p < 0.05). Low initial infusion rate was strongly but not
      significantly predictive of inadequate anticoagulation (p = 0.06). The mean
      heparin bolus and initial infusion rates were significantly lower than those
      suggested in the literature (p < 0.01). The AH rates were comparable to
      historical controls but suboptimal compared with the rates of 66% at 24 hours and
      81% at 48 hours reported in association with heparin nomogram use (p < 0.05). A
      heparin nomogram is likely to achieve consistently higher rates of adequate
      heparinization.

PMID- 7562126
TI  - Health insurance does not guarantee access to primary care: a national study of
      physicians' acceptance of publicly insured patients.
AB  - The roles of reimbursement and other predictors that affect physicians'
      willingness to accept publicly insured continuing care patients were examined in
      a national survey. The response rate was 47%. Eighty-eight percent of the
      respondents were accepting new patients. Forty-two percent of these physicians
      were willing to accept new continuing care patients insured by Medicaid, 70%
      reported accepting those paying by Medicare assignment, and 85% said they accept
      patients covered by Medicare plus balance-billing payments. Low reimbursement was
      the strongest predictor for lack of acceptance. The results suggest that systems
      of multitiered reimbursement are associated with diminished access for patients
      insured in the lower tiers.

PMID- 7562127
TI  - The primary care pathway to mammography: a long and winding road.

PMID- 7562128
TI  - Thrombolytic therapy: just do it.

PMID- 7562129
TI  - Teaching an old dog new tricks.

PMID- 7562130
TI  - Cardiac rehabilitation factors.

PMID- 7562131
TI  - Human parvovirus B19 in pregnancy.
AB  - Human parvovirus is an often unrecognized but potentially deadly infection when
      contracted by childbearing women who are seronegative. Although maternal symptoms
      and sequelae are mild, the exposed fetus quickly can develop nonimmune hydrops
      fetalis and die. Health care providers can prepare for appropriate maternal and
      fetal management by reviewing the history, disease process, and transmission mode
      of parvovirus.

PMID- 7562132
TI  - Comparison of kangaroo and traditional methods of removing preterm infants from
      incubators.
AB  - OBJECTIVE: To compare the kangaroo and traditional methods of removing an infant
      from an incubator in terms of four physiologic parameters, mother's satisfaction,
      and mother's preference. DESIGN: Time-series design (quasi-experimental), with
      infant-mother dyads subjected to both methods. SETTING: Intermediate neonatal
      care unit in a tertiary hospital in Canada. PARTICIPANTS: A convenience sample of
      71 infant-mother dyads. INTERVENTION AND MEASURES: The intervention was use of
      the kangaroo or traditional method of maintaining body temperature of preterm
      infants. The dependent variables were physiologic parameters (skin temperature,
      heart rate, respiratory rate, and oxygen saturation) measured five times with
      each method. Mother's satisfaction was measured at the end of each testing period
      and mother's preference at the end of the experiment. RESULTS: The kangaroo
      method produced less variation in oxygen saturation and longer duration of
      testing, and it was preferred by most of the mothers. CONCLUSIONS: The kangaroo
      method is safe for the preterm infant and allows for early contact between
      parents and infants.

PMID- 7562133
TI  - Fathers' parenting attitudes during a child's first year.
AB  - OBJECTIVE: To determine whether fathers' interactions with their children from
      prebirth to 1 year of age changed the fathers' parenting attitudes as measured by
      the Adult-Adolescent Parenting Inventory (AAPI). DESIGN: Nonrandomized,
      longitudinal, descriptive study. SETTING: Private obstetricians' offices,
      prenatal clinics, and prenatal classes in a large city in the southeastern United
      States. PARTICIPANTS: White, well-educated, stable, upper-middle class fathers
      attending prenatal education classes. At time 1 (prebirth), n = 293 with 228
      first-time fathers and 65 experienced fathers. At time 2 (3 months), n = 62 with
      46 first-time fathers and 16 experienced fathers. At time 3 (1 year), n = 42 with
      30 first-time fathers and 12 experienced fathers. MAIN OUTCOME MEASURES:
      Parenting attitudes as measured by the AAPI. RESULTS: Repeated measures analysis
      of variance revealed a significant difference in two of the four constructs
      measured by the AAPI. When their children were 3 months old, fathers scored
      significantly lower in the areas of expectations and belief in the use of
      corporal punishment, and their raw scores did not significantly differ in the
      areas of empathy and appropriate family roles. CONCLUSION: These fathers need
      education about appropriate expectations of a 3-month-old child and information
      regarding alternative methods of discipline.

PMID- 7562134
TI  - The long-term psychosocial effects of infertility.
AB  - OBJECTIVE: To explore the psychosocial effects of infertility and the role that
      social support plays over time. The major hypothesis was that although infertile
      persons report less contentment, lower levels of marital and sexual satisfaction,
      and lower self-esteem over time, those with higher levels of social support will
      be less affected. DESIGN/SETTING: Four questionnaires were completed in subjects'
      own homes, one every 9 months. PARTICIPANTS: Subjects, all of whom perceived
      themselves as infertile, were recruited through the national newsletter for an
      infertility support group. Ninety-four subjects entered the study, and 41% of the
      sample completed it. MAIN OUTCOME MEASURES: Contentment, marital satisfaction,
      sexual satisfaction, self-esteem, sex-role identity, press (the measure of
      perceived internal and external pressures), and social support. RESULTS:
      Perceived support (F[3, 111] = 4.77, p < 0.004), as well as contentment and self
      esteem, significantly increased over time (F[3, 111] = 12.03, p < 0.0001, and
      F[3, 111] = 5.378, p < 0.002, respectively). Social support was positively
      correlated with all dependent measures. CONCLUSIONS: Contrary to what was
      hypothesized, infertile persons experienced increased social support and greater
      contentment over time. As hypothesized, there was a significant positive
      relationship between social support and all dependent measures. The positive
      impact of social support, counseling, and the adoption of strategies to deal with
      the stress of infertility lends credence to the crucial role nurses can play in
      helping infertile couples cope.

PMID- 7562135
TI  - The impact of recent advances in microbiology and immunology on perinatal and
      women's health care.
AB  - Microbiology and immunology have offered important advances in the care of women
      and newborns. Understanding of the interplay between individuals and the
      microorganisms associated with them has provided the framework for important
      changes in practice. An excellent historical example of this idea, well known to
      nurses, involves puerperal fever. A recent example is knowledge of the
      relationship of breastfeeding and human immunodeficiency virus. Recent advances
      in microbiology and immunology that have improved women's health include improved
      diagnostic tests and a more complete understanding of the vaginal biofilm.

PMID- 7562136
TI  - Nurses: at special risk.
AB  - Nurses are at occupational risk for many infections, but it was not until human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) was
      recognized that a work-acquired infection was uniformly fatal. Other work
      acquired infections, including tuberculosis, rubella, measles, varicella, and the
      viral hepatitides, may cause morbidity for the nurse and his/her family. Although
      the number of nurses who acquire occupational infections is small, each has a
      unique personal story, and all will have their productivity affected. A few will
      lose their lives to infections acquired on the job. Although all occupational
      infections cannot be prevented, understanding the chain of infection and how to
      break the links can go a long way in reducing risks and maintaining health for
      all health care workers.

PMID- 7562137
TI  - Infections during the postpartum period.
AB  - Postpartum infections are costly in terms of delayed mother-infant interaction;
      lactation difficulties; prolonged hospital stay or readmittance to the hospital
      and increased expense; and possible permanent injury or death. The nurse is in a
      unique position to identify the woman at risk, recognize early warning signs, and
      provide teaching and counseling for prevention and care. Shortened hospital stays
      challenge the nurse to develop, research, and discover funding for new
      interventions to provide care and teaching to minimize the effects of this
      problem.

PMID- 7562138
TI  - Sepsis during pregnancy.
AB  - The incidence of maternal mortality related to sepsis has decreased during the
      past 2 decades because of the availability of broad spectrum antibiotics and
      advances in critical care. However, sepsis continues to account for approximately
      7.6% of maternal deaths in the United States. This article focuses on
      intraamniotic infection as a source of maternal sepsis. Common causative
      pathogens, typical sources of sepsis, and related pathophysiology are reviewed.
      Nursing and medical management strategies are included. A case study is presented
      to illustrate the typical clinical course from infection, to bacteremia, sepsis,
      and septic shock.

PMID- 7562139
TI  - Toxic shock syndrome: an opportunity for nursing intervention.
AB  - Toxic Shock Syndrome (TSS) is a potentially fatal illness caused by a particular
      strain of Staphylococcus aureus. The clinical presentation is similar to that of
      septic shock. The incidence of TSS peaked in the late 1970s and early 1980s,
      probably as a result of availability of super absorbent tampons. Although most
      commonly associated with menstruation, the overall incidence of menstrual and
      nonmenstrual TSS in men and women ranges from 1 to 3 per 100,000. There are
      almost equal numbers of menstrual and nonmenstrual cases of TSS identified
      annually. S aureus, the causative microorganism in cases of TSS, has been
      isolated from many body tissues. Toxic shock syndrome presents as a flu-like
      illness with high fever, vomiting, diarrhea, general malaise, and muscle
      weakness. Nursing and medical management focus on controlling or preventing
      potentially serious complications, such as adult respiratory distress syndrome,
      renal failure, electrolyte imbalances, disseminated intravascular coagulation,
      encephalopathy, and cardiomyopathy. Judicious use of tampons and barrier
      contraceptive devices may decrease the risk of developing TSS.

PMID- 7562140
TI  - Group B streptococcus during the perinatal period.
AB  - The beta hemolytic streptococcus group B (GBS) emerged as a major pathologic
      threat to infants in the 1960s and continues to be the leading cause of maternal
      and neonatal morbidity in the 1990s. Current approaches to prevention are
      directed toward eliminating exposure to the pathogen through chemoprophylaxis or
      enhancing host resistance through immunoprophylaxis. Because research is
      advancing rapidly in this area, perinatal nurses should keep abreast of changes
      in prevention and treatment strategies to enhance patient education and improve
      care.

PMID- 7562141
TI  - Pancreatic adenocarcinoma presenting as a splenic abscess: case report and
      diagnostic approach.
AB  - As the fourth leading cause of cancer death in the United States, pancreatic
      adenocarcinoma is both a diagnostic and a therapeutic challenge. Its incidence
      has risen in the past four decades so that pancreatic cancer ranks second to
      colon cancer as a leading cause of death from gastrointestinal malignancy.
      Despite technical and therapeutic advances, the prognosis remains dismal; the
      average survival time after diagnosis is characteristically only five to eight
      months. The current patient had a pancreatic adenocarcinoma that mimicked other
      disorders. Variability in clinical presentation and imaging studies warrants
      consideration of this entity in the differential diagnoses of many splenic and
      pancreatic lesions.

PMID- 7562142
TI  - Vasoactive intestinal peptide and nerve growth factor effects on nerve
      regeneration.
AB  - Sixty rat sciatic nerves were used to study the effects of vasoactive intestinal
      peptide (VIP) and nerve growth factor (NGF) on nerve regeneration. They were
      divided into three groups. Groups 1 and 2 were treated with VIP and NGF,
      respectively, after dividing the nerves without repair and placing them in
      silastic chambers. Group 3 served a control. The rate and quality of nerve
      regeneration were compared among the groups using caliper measurements and
      histologic evaluation. Both VIP and NGF groups showed an enhanced rate of
      regeneration at three weeks as compared to controls (p < 0.05). The quality of
      nerve regeneration histologically and by axonal counting was not significantly
      different among the three groups, except for the presence of less vascularity in
      the VIP as compared with the NGF group. In addition to NGF, VIP appears to
      increase the rate of nerve regeneration as compared to controls.

PMID- 7562144
TI  - The ABCs of chronic hepatitis: reason out of confusion.
AB  - Chronic hepatitis is defined as a condition in which liver injury tests
      (aminotransferases or cholestatic enzymes such as alkaline phosphatase) are
      abnormal on several occasions (usually determined monthly) for more than 6
      months. The causes or the disease processes that can lead to chronic hepatitis
      are numerous, making the diagnosis and particularly the evaluation of patients
      with chronic hepatitis difficult or even mystical for those who do not identify
      themselves primarily as hepatologists. It is for these latter individuals (the
      bulk of practicing gastroenterologists and physicians in other primary fields)
      that the following editorial is written. It is hoped that a structured approach
      to the problem of chronic hepatitis will enable these physicians to make
      decisions concerning specific disease etiologies and, as a result, medical
      therapies for chronic hepatitis for their patients and that these decisions be
      both rational and simple. The system to be presented has been utilized by the
      author for over a decade and has been found to be very useful in training medical
      and surgical house officers as well as gastroenterology fellows and has been
      equally useful for the faculty of gastroenterology and hepatology programs. It is
      currently being used in Oklahoma at the Oklahoma Transplantation Institute and
      Hepatic and Digestive Diseases Center of Baptist Hospital in Oklahoma City.

PMID- 7562143
TI  - A statewide, toll-free telephone service to improve obstetric care.
AB  - The University of Oklahoma Health Sciences Center began in 1993 to provide a
      statewide, toll-free telephone service for pregnancy counseling to primary care
      physicians. The service was available 24 hours each day, and responses were made
      by the on-call maternal-fetal medicine specialist. This report summarizes our
      first full year of operation. Inquiries came from 34 (63%) of the state's 54
      counties having physicians who provide obstetric care. One hundred twenty-eight
      physicians made 523 inquiries (median 3, range 1-15). Information was sought
      about prenatal genetic disorders, risks from drugs, exposure to infection,
      environmental hazards, and active obstetric or medical complications. Funds from
      targeted ultrasounds, genetic amniocenteses, more detailed counselling, and
      maternal transfers provided support for this expanding educational resource.

PMID- 7562145
TI  - Oklahoma kids and tobacco: the problem is still growing.

PMID- 7562146
TI  - Pittsburgh University questions paper.

PMID- 7562147
TI  - Degenerative arthritis after tibial plateau fractures.
AB  - Secondary osteoarthritis after tibial plateau fracture was found in 44% of 131
      cases at 7.6 (3.3-13.4) years follow-up. Narrowing of the joint space was noted
      during the first 7 years after injury, usually in the same compartment as the
      fractured plateau. The incidence slightly increased with the age of patients.
      Removal of a meniscus during the fracture surgery resulted in secondary
      degeneration in 74% of the cases. When a meniscus was intact or repaired, the
      proportion of degenerative cases was only 37%. Normal or slight valgus alignment
      of the tibial plateau with intact menisci protected best against secondary
      degeneration. On the other hand, medial or lateral tilt of the tibial plateau
      with a removed meniscus was followed by osteoarthritis in most cases. The
      severity of articular irregularities correlated poorly with the degenerative
      process. Associated ligamentous injuries as well as postoperative infection
      increased the incidence of secondary degeneration.

PMID- 7562148
TI  - Indirect reduction and internal fixation of supracondylar femur fractures without
      bone graft.
AB  - Thirty supracondylar-intercondylar fractures of the distal femur were treated in
      a prospective series using an indirect reduction technique. From January 1988 to
      July 1993, patients who entered into this protocol had undergone fixation with a
      distal lateral plate without stripping of the medial soft tissues and without
      bone graft. With this technique, 86.6% excellent and satisfactory results were
      achieved using the Neer rating system. Of the three failures, two were in
      elderly, osteoporotic women with comminuted intraarticular fractures, and one
      failure occurred in a renal transplant patient with bilateral quadriceps ruptures
      despite a good result from her femur fracture. Only one patient with a grade 2
      open fracture and comminution developed a nonunion, which eventually healed after
      bone grafting. The results of this technique compare favorably with other series
      of osteosynthesis of supracondylar femur fractures in the orthopaedic literature
      without the added morbidity associated with autogenous bone grafting. The
      surgical technique is demanding and may not be suitable for patients with severe
      open fractures with devascularized bony fragments or marked osteoporosis.

PMID- 7562149
TI  - Distal femoral nonunion: treatment with a retrograde inserted locked
      intramedullary nail.
AB  - Between March 1989 and August 1993, 16 distal femoral nonunions (16 patients)
      were treated using the supracondylar intramedullary nail. The time between the
      initial event and retrograde nailing averaged 33 months. The nonunion level was
      infraisthmal in four patients and supracondylar in 12. Operative technique
      involved retrograde insertion of a reamed supracondylar intramedullary nail
      through the intercondylar notch. Follow-up was available on all patients and
      averaged 20 months (range 9-46). Four nonunions (25%) united with a single
      surgery at an average of 17 months. A fifth nonunion united at 21 months after
      nail dynamization and subsequent nail breakage. The nonunions of two additional
      patients united after exchange of a broken retrograde nail. Additional surgical
      procedures were performed in six of the remaining nine patients in an attempt to
      gain union. At an average follow-up of 16 months (range 9-23), none of the nine
      had united. Nine nails fractured at an average of 11 months, all through a screw
      hole near the nonunion. Based on these results, we cannot recommend use of the
      supracondylar intramedullary nail in its present form for the treatment of distal
      femoral nonunions.

PMID- 7562150
TI  - Treatment of unstable peritrochanteric fractures in elderly patients with a
      compression hip screw or with the Vandeputte (VDP) endoprosthesis: a prospective
      randomized study.
AB  - A prospective randomized study was set up, comparing a compression hip screw with
      the Vandeputte (VDP) endoprosthesis treatment for fresh, unstable
      peritrochanteric fractures, according to the Evans-Jensen and AO systems. Ninety
      patients, ages > or = 70 years, 47 of whom were treated with a compression hip
      screw and 43 with a VDP endoprosthesis, were included. All patients were being
      followed for 3 months. No difference between the two groups was found for
      operating time, wound complications, and mortality rate, but there was a higher
      transfusion need in VDP treatment. Severe fracture redisplacement or total
      collapse of the fracture occurred in 11 (26%) compression hip screw patients, two
      of whom had revision surgery. Only one patient needed reintervention after VDP
      treatment. Functional capacity of preoperative independent patients at hospital
      discharge did not differ for the two groups. In conclusion, the compression hip
      screw seemed to be an appropriate implant for most of the peritrochanteric
      fractures, but for very old patients with advanced osteoporosis, with a complex,
      unstable peritrochanteric fracture, and who are eligible for early mobilization,
      primary cemented endoprosthesis might be the best treatment.

PMID- 7562151
TI  - Modular unipolar versus bipolar prosthesis: a prospective evaluation of
      functional outcome after femoral neck fracture.
AB  - Between January 1, 1987, and December 31, 1992, 140 community-dwelling geriatric
      patients > or = 65 years of age with a displaced femoral neck fracture (Garden
      III-IV) underwent primary prosthetic replacement and were followed prospectively
      for a minimum of 1 year. Overall, 92 patients received a cemented bipolar
      prosthesis and 48 patients received a cemented modular unipolar prosthesis. There
      were no statistically significant differences between the two groups with respect
      to preinjury characteristics (age, sex, and number and severity of medical
      comorbidities) and functional ability. There were no statistically significant
      differences between the two groups with regard to the number of postoperative
      complications, length of stay, and 1 year mortality rate. An in-depth functional
      evaluation was obtained as follows: level of ambulation, independence in basic
      activities of daily living (feeding, bathing, dressing, toileting), and
      independence in instrumental activities of daily living (food shopping, food
      preparation, banking, laundry, housework, and use of public transportation). At 1
      year follow-up, no statistically significant differences in functional ability
      were identified between the unipolar and bipolar groups. Furthermore, at a
      minimum of 1 year follow-up, there were no statistically significant differences
      between the two groups with regard to the need for revision surgery or the
      incidence hip pain. Based on the results of this study, there does not appear to
      be any advantage to the use of bipolar endoprosthesis for the treatment of
      femoral neck fractures in the elderly patient. The lower cost of modular unipolar
      prostheses compared with bipolar prostheses provides additional support for their
      use.

PMID- 7562152
TI  - Toxic effects of wound irrigation solutions on cultured tibiae and osteoblasts.
AB  - Irrigating wounds with solutions of antiseptic or antibiotic agents is routinely
      performed in orthopaedic surgery to reduce the incidence of microbial infection.
      The effects of these agents on healthy bone tissue is unknown. Three commonly
      employed antiseptic agents (hydrogen peroxide, Betadine solution, Betadine scrub)
      and one antibiotic solution (bacitracin) were tested on tibiae and osteoblasts
      isolated from embryonic chicks. Osteoblast function was evaluated by glycolytic
      energy metabolism (lactate production), cell number (DNA content), and collagen
      synthesis ([3H]proline hydroxylation). Two series of experiments were performed.
      To study concentration-related effects, tibiae or cells were exposed to a range
      of concentrations of the agents (diluted in saline, 0.9% NaCl) for 2 min, rinsed
      with saline, and incubated for 24 h in medium containing [3H]proline. For the
      recovery study, the cells were exposed to an effective, but nonlethal,
      concentration of the antiseptic agents for 2 min, rinsed with saline, and the
      incubation was continued in complete culture medium for 6, 12, 24, 48, or 72 h
      with [3H]proline added for the final 6 h. Solutions containing the antiseptic
      agents were cytotoxic to both bones and cells at concentrations well below those
      used clinically in irrigation solutions. In contrast, bacitracin at the
      concentrations tested was safe for osteoblasts and tibiae. These results suggest
      that the use of irrigation solutions containing H2O2, Betadine solution, or
      Betadine scrub on exposed bone tissue should be considered with caution.

PMID- 7562153
TI  - Titanium anchors for the repair of rotator cuff tears: preliminary report of a
      surgical technique.
AB  - We used titanium anchors for the surgical repair of rotator cuff tears in 34
      selected patients, all of whom were < 60 years of age, had good bone quality, and
      had no known metabolic bone diseases. Nine tears were repaired within 6 months,
      15 within 6-12 months, and 10 later than 12 months after injury. Tear size was
      graded as small (10 patients), medium (15 patients), and large (nine patients)
      during open operation. After 6-24 months of follow-up, 30 patients reported
      satisfactory pain relief, function, active forward flexion, and muscle strength
      [18 excellent and 12 good results based on the University of California at Los
      Angeles rating system (UCLA scores)]; there were no implant failures (p < 0.001).
      Two patients had unsatisfactory function but good relief of pain, whereas two
      patients were dissatisfied with their overall result (four poor results based on
      UCLA scores). Although trans-bone suturing is presently the most common and
      successful surgical technique for rotator cuff tears, we found that use of
      titanium anchors shortens operative time and has results comparable with the
      traditional technique. Titanium anchors should not be used when bone quality is
      poor or good patient compliance is doubtful. They are also contraindicated, as
      our four poor results indicate, when the tear is old (> 6 months) and large
      (diameter > 5 cm with significant tissue degeneration).

PMID- 7562154
TI  - Fractures of the radial head treated by internal fixation: late results in 26
      cases.
AB  - Twenty-six patients, ranging in age from 14 to 57 years (average 29 years), were
      evaluated an average of 7 years and 4 months (range 1-14 years) after open
      reduction and internal fixation of a displaced radial head fracture. Using
      Mason's classification, there were 11 type II fractures, 9 type III fractures,
      and 6 type IV fractures with associated dislocation of the elbow. Seven patients
      had ipsilateral extremity injuries that included fractures of the coronoid
      process, capitellum, humerus, and distal radius. Using the Broberg and Morrey
      elbow score, good or excellent results were achieved in all Mason type II and
      type III fractures. Four of the six Mason type IV fractures were rated good or
      excellent. Fair results were obtained in two patients who had an associated
      dislocation of the elbow and multiple ipsilateral extremity injuries. In these
      two patients, secondary excision of the radial head relieved pain and yielded
      some improvement in flexion and forearm rotation.

PMID- 7562155
TI  - Measurement of serum angiogenic factor in devascularized experimental tibial
      fractures.
AB  - Early recovery of the vasculature is of profound importance in healing fractures,
      but the exact role of the regenerating endothelium remains controversial. Serum
      activity of endothelial cell-stimulating angiogenesis factor (ESAF) was measured
      after tibial osteotomy in two groups of sheep over a period of 42 days. Each
      osteotomy was held in an instrumented external fixator, and in one group the
      musculoperiosteal vasculature was excluded from the osteotomy site. In the well
      vascularized group (n = 4), ESAF activity was significantly higher 2-5 days after
      osteotomy, with a peak at 4 days (21.1 +/- 5.4, p < 0.05), and displayed a
      biphasic pattern of secretion with a second peak at 7 days (24.3 +/- 5.5). In the
      devascularized group (n = 4) overall activity was lower, with only a single peak
      occurring at 9 days (17.5 +/- 3.2). These findings were correlated with
      significant differences in structural properties and on histological examination.
      The early detection of such regional vascular responses may prove to be of
      significant clinical value in high-energy trauma, enabling prediction of those
      fractures at risk of delayed or nonunion.

PMID- 7562157
TI  - Reimplantation of a contaminated and devitalized bone fragment after autoclaving
      in an open fracture.
AB  - This case report describes a technique for dealing with open fractures with
      segmental bone loss and a critical need for restoration of anatomical alignment.
      In the majority of cases, autogenous bone graft can and should be used
      successfully. Regardless of the treatment option chosen though, meticulous
      debridement and sound judgment in regards to wound care and bony stabilization
      remain the foundation to a successful outcome. Autoclaving a devitalized bone
      fragment with subsequent reimplantation as described in this case report,
      although not the procedure of choice, does offer the orthopaedist another option
      in dealing with the difficult segmental fracture.

PMID- 7562156
TI  - A simple external fixator for use in metacarpal and phalangeal fractures: a
      technique paper.
AB  - We report the use of a simple and inexpensive external fixator for the treatment
      of unstable, displaced metacarpal and phalangeal fractures in a series of 12
      patients. The fixator was well tolerated and the clinical and radiological
      results were excellent in all cases.

PMID- 7562158
TI  - Controversies on the treatment of irreducible elbow dislocations with an
      associated nonsalvageable radial head fracture.
AB  - We report the case of a 26-year-old man who sustained an elbow dislocation with
      an associated radial head fracture entrapped in the joint, preventing closed
      reduction. A posterolateral approach to the radial head was performed to reduce
      the dislocation. A comminuted fracture of the entire radial head was found that
      required excision. Although radial head replacement has been stressed to restore
      sufficient stability in similar cases (because most are inherently unstable), it
      is important to determine whether the ulnar collateral ligament (UCL) is intact.
      Intraoperative use of valgus stress aids in that determination. The radial head
      can then be excised if the UCL is intact. In this case, no instability resulted
      with excision of the radial head because the UCL was intact. Failure to recognize
      and/or to treat an UCL rupture associated with radial head excision can result in
      elbow instability, increased elbow valgus deformity, and ulnohumeral arthritis.

PMID- 7562159
TI  - Burst fracture of the fifth lumbar vertebra in combination with a pelvic ring
      injury.
AB  - A burst fracture at the L5 level is a rare injury. To our knowledge, there have
      been no accounts of a concomitant, unstable pelvic ring injury. This report
      details the treatment and 2-year follow-up of such an unusual case. It is of
      interest that the two injuries are seemingly caused by different mechanisms, and
      issues in management are raised.

PMID- 7562161
TI  - Lumbosacral fracture-subluxation associated with bilateral fractures of the first
      sacral pedicles: a case report and review of the literature.
AB  - A case of an unusual lumbosacral fracture-subluxation associated with bilateral
      fractures of the first sacral pedicles is described. The authors are aware of
      only one reported case in the literature. A 58-year-old man was involved in an
      accident during which his trunk was severely twisted toward the left and flexed.
      He also demonstrated L5 and S1 radiculopathies. He was successfully treated with
      surgical decompression of the L5 and S1 nerve roots with bilateral
      foraminotomies, followed by posterolateral arthrodesis at the lumbosacral
      junction using a transpedicular screw system that extended fixation into the
      ilia.

PMID- 7562160
TI  - Late-onset sternomanubrial dislocation with progressive kyphotic deformity after
      a thoracic burst fracture.
AB  - Fractures and dislocations of the sternum may be associated with flexion
      compression injuries of the thoracic spine. Sternal injuries most commonly occur
      at or near the sternomanubrial joint. We present a patient with a known thoracic
      spine fracture who developed a subsequent late-onset, symptomatic sternomanubrial
      dislocation and progression of thoracic kyphosis, ultimately requiring operative
      fixation of both the sternum and the spine. Internal fixation of these sternal
      injuries should be considered in the setting of a flexion-compression thoracic
      spine fracture to possibly prevent a worsening kyphosis and neurological decline.

PMID- 7562162
TI  - Distal femur as bone graft donor site.

PMID- 7562163
TI  - Exercising your health care rights.

PMID- 7562164
TI  - Infection following treatment of mandibular fractures in human immunodeficiency
      virus seropositive patients.
AB  - PURPOSE: There are little data available on the prevalence of human
      immunodeficiency virus (HIV) disease and its relationship to postoperative
      infection in patients presenting with mandibular fractures. This retrospective
      study assesses these parameters. PATIENTS: The study population consisted of 251
      patients treated for mandibular fractures at San Francisco General Hospital
      (SFGH) between January 1990 and December 1993. Group 1 (n = 20) was composed of
      patients with documented HIV infection and group 2 (n = 231) served as controls.
      The groups were comparable with regard to age, sex, etiology, and number and
      types of fractures. RESULTS: HIV prevalence for this population was 7.9%, and was
      consistent with previously documented prevalence studies in SFGH surgical
      patients. In the HIV-positive group, 6 of 20 patients (30%) developed
      postoperative infection: 2 soft tissue (10%) and 4 bone-related (20%). In the
      control group, 22 of 231 patients (9.5%) developed postoperative infections: 16
      soft tissue (6.9%) and 6 bone-related (2.6%). Statistical analysis showed a
      significant difference between the two groups with regard to overall (P = .016)
      and to bone-related (P = .001) infection rates. There was no statistically
      significant difference in soft tissue infections between the two groups (P =
      .953). The rate of postoperative infection was significantly higher in those
      patients (both HIV-positive and controls) who had open reduction and internal
      fixation (ORIF; 25/155; 16%) versus those who had closed reduction and
      maxillomandibular fixation (3/96; 3.1%; P = .003). The postoperative infection
      rate after ORIF was significantly higher in the HIV-positive (5/11; 45%) compared
      with the control group (20/144; 13.9%; P = .02). CONCLUSIONS: The results of this
      study indicate that the overall rate of postoperative infection after treatment
      of mandibular fractures is significantly higher in HIV-positive than in HIV
      negative patients. Specifically, the use of ORIF in HIV-positive patients
      represents a significant risk.

PMID- 7562167
TI  - The cranial base in obstructive sleep apnea.
AB  - PURPOSE: The purpose of this investigation was to determine if there are cranial
      base differences in adults with obstructive sleep apnea (without identifiable
      craniofacial abnormalities) when compared with those of adults without airway
      problems. METHODS: Cephalometric analysis of the cranial base of 52 patients with
      documented sleep apnea were compared with 96 normal adult patients. Each of the
      groups was subdivided based on skeletal profiles (Class I, II, III).
      Cephalometric measurements included cranial base flexure angle and anterior and
      posterior cranial base lengths. Standard analysis of variance and Students' t
      test were used to determine level of significance. RESULTS: The cranial base
      flexure angle in patients with documented sleep apnea was significantly more
      acute than that found in the nonapnea group. Patients with a skeletal Class III
      profile had the most acute cranial base flexure whereas those with Class II
      profiles had the most obtuse angles. This pattern was true for apnea and nonapnea
      groups. No cranial base length differences could be found in either group.
      CONCLUSION: The results of this study demonstrate that there were abnormalities
      of the cranial base in patients with obstructive sleep apnea. Abnormalities of
      the cranial base seen in "nonsyndrome" obstructive sleep apnea patients are
      similar to those seen in patients with certain identifiable syndromes. This may
      suggest that sleep apnea is a reflection of a form of craniofacial syndrome.

PMID- 7562165
TI  - Evaluation of topical viscous 2% lidocaine jelly as an adjunct during the
      management of alveolar osteitis.
AB  - PURPOSE: This study evaluated the efficacy of topical viscous 2% lidocaine jelly
      for the alleviation of pain experienced during the instrumentation of mandibular
      third molar extraction sites diagnosed with alveolar osteitis and for pain relief
      during the postinstrumentation period. PATIENTS AND METHODS: Thirty adult
      patients with a diagnosis of alveolar osteitis in a mandibular third molar
      extraction site were included in this prospective, double-blind study. Each
      patient had their sutures removed, the socket irrigated, and 2% lidocaine jelly
      placed on the tip and side of the tongue to blind the patient against the test
      substances. The subjects were then randomly distributed into two groups. Group 1
      had a nonactive jelly base placed into the socket 2 minutes prior to the
      placement of a standard obtundant dressing. Group 2 had viscous 2% lidocaine
      jelly placed into the socket in the same manner. Patients subjectively quantified
      their pain intensity pretreatment, during instrumentation, immediately
      postmanipulation, at 5-minute intervals to 30 minutes, and at 45 and 60 minutes.
      They also subjectively quantified their pain relief at each of the time intervals
      following instrumentation. RESULTS: There was no statistical difference between
      the pretreatment pain experienced by both groups. The use of 2% lidocaine jelly
      had a measurable (P = .056), but not statistically significant, effect on pain
      due to instrumentation. At every time interval thereafter, the use of 2%
      lidocaine jelly elicited a statistically significant (P < .05) decrease in pain
      perception, and a statistically significant increase in pain relief when compared
      with the inactive jelly. CONCLUSION: Topical viscous 2% lidocaine jelly is a
      useful adjunct during the treatment of alveolar osteitis, especially in the early
      (< or = 60 minutes) postinstrumentation period.

PMID- 7562166
TI  - Craniomaxillofacial trauma in the elderly.
AB  - PURPOSE: Limited data are currently available regarding the nature of
      craniomaxillofacial fractures in the geriatric population. This retrospective
      study reviews 109 hospital records dating from 1981 to mid-1993. The goal of this
      study was to provide details relevant to these types of injuries. RESULTS: Most
      patients were injured in motor vehicle accidents (MVA) or fall-related episodes.
      Females sustained 43.9% of the fractures while males sustained 56.1%. In females,
      falls were the most common cause of fractures, while in males MVAs caused the
      majority of fractures (P < .01). Most fractures were found in the upper midface
      region (60.3%) and the mandible (27.5%). MVAs and falls were responsible for
      82.7% of all mandibular fractures. The majority of fractures were treated
      nonsurgically (49.5%); however, 37.6% were treated with open reduction and
      internal fixation. The in-hospital mortality rate was 11.1%, and there were three
      postoperative complications. CONCLUSION: The geriatric craniomaxillofacial trauma
      patient is readily treatable with both aggressive surgical measures and more
      conservative approaches. Elderly patients often have an underlying medical
      condition that may subsequently alter the patient's treatment. The findings of
      this study also suggest that more preventive measures and methods of minimizing
      mortality and morbidity need to be implemented.

PMID- 7562168
TI  - The effect of quiet tidal breathing on lateral cephalometric measurements.
AB  - PURPOSE: In the evaluation of the upper airway in patients with sleep apnea it
      has been suggested that cephalometric radiographs be performed at either end
      inspiration or end-expiration during quiet tidal breathing. This study sought to
      determine if standard soft tissue cephalometric measurements vary significantly
      with tidal breathing. PATIENTS AND METHODS: In this prospective, controlled study
      22 adult male patients with the sleep apnea/hypopnea syndrome and 27 nonapneic,
      nonsnoring male controls had cephalometric radiographs performed at end-tidal
      inspiration and end-tidal expiration. The measurements obtained from each
      radiograph included the posterior airway space distance, the mandibular plane to
      hyoid distance, and the posterior nasal spine to tip of palate (PNS-P) distance.
      RESULTS: There were no statistically significant differences between the
      inspiratory and expiratory measurements in either group. Only the PNS-P distance
      differed significantly between the two groups. Changes in cephalometric
      measurements did not occur uniformly in any one direction with tidal breathing.
      CONCLUSION: The data indicate that coordinating radiographic exposure to
      respiratory cycle phase is not necessary for soft-tissue measurements commonly
      used to assess upper airway patency in patients with the sleep apnea/hypopnea
      syndrome.

PMID- 7562169
TI  - Postoperative computed tomography scan study of the pterygomaxillary separation
      during the Le Fort I osteotomy using a micro-oscillating saw.
AB  - PURPOSE: The objective of the study was to evaluate the type of pterygomaxillary
      separation that occurs with use of a micro-oscillating saw. PATIENTS AND METHODS:
      Sixteen patients underwent a postoperative computed tomography scan. RESULTS:
      Ideal or near-ideal separations occurred on 26 of 32 sides (81%), while low-level
      fractures occurred in 6 of 32 sides (19%). No high-level fractures of the
      pterygoid plates, or fractures extending to the base of the skull or orbit, were
      seen. There was a striking difference in the number of ideal separations on the
      right-hand side (94%), compared with the left-hand side (50%), probably because
      of the greater difficulty of a right-handed surgeon positioning the saw blade
      correctly on the left side without bending the thin flexible saw blade backward.
      CONCLUSION: In view of the high percentage of ideal pterygomaxillary separations
      achieved using a micro-oscillating saw, and the absence of high-level pterygoid
      plate fractures extending to the base of the skull, this technique is recommended
      for the pterygomaxillary dysjunction.

PMID- 7562170
TI  - Patient satisfaction and chewing ability with implant-retained mandibular
      overdentures: a comparison with new complete dentures with or without
      preprosthetic surgery.
AB  - PURPOSE: The objective of this study was to compare denture satisfaction and
      chewing ability of edentulous patients treated with dental implant-retained
      overdentures or with full dentures with or without previous preprosthetic
      surgery. PATIENTS AND METHODS: This study was a controlled clinical trial. Thirty
      eight men and 52 women participated in the study. The mean height of the anterior
      mandible was 21 mm (range, 16 to 25 mm), measured on a lateral cephalometric
      radiograph. The subjects were randomly assigned to the three treatment
      modalities. The main outcome measures were denture satisfaction and chewing
      ability, which were assessed using questionnaires focusing on denture-related
      complaints and the ability to chew different types of food, and an overall
      denture satisfaction score. RESULTS: Based on the baseline data from the "denture
      complaints" and "chewing ability" questionnaires, nine interpretable factors
      could be extracted. Two factors did not vary following treatment and were
      excluded from the outcome analysis. At the 1-year evaluation five of seven
      factors showed significantly better scores for the two surgical groups than for
      the control group. The same was found for the overall denture satisfaction rate.
      CONCLUSION: Overdentures retained by dental implants or complete dentures made
      after a vestibuloplasty and deepening of the floor of the mouth provide a more
      satisfactory solution for denture-related problems than complete dentures alone.
      For the scale "functional complaints lower denture," the overdenture group showed
      even a significantly better score than the preprosthetic surgery group.

PMID- 7562171
TI  - A prospective study of the efficacy of various gloving techniques in the
      application of Erich arch bars.
AB  - PURPOSE: This is a prospective study of the efficacy of three different
      techniques of triple gloving during the application of Erich arch bars. Two
      different cut-resistant glove liners and three layers of latex gloves were
      compared with double gloving. METHODS AND MATERIALS: Thirty patients underwent
      Erich arch bar placement from first molar bilaterally on both arches. Two
      surgeons per case were arbitrarily placed into one of four groups that included
      double latex gloving, triple gloving with kevlar or stainless steel glove liners,
      or triple layer latex gloving, based on the availability of glove liners. All
      gloves were collected postoperatively and tested for perforation using water
      insufflation. RESULTS: One hundred eight of 120 outer gloves were perforated.
      There were 16 perforations in 11 inner gloves of the double latex glove group,
      but no perforations in the inner gloves of the triple latex glove group. There
      were two inner gloves with one perforation each in the stainless steel group and
      one glove with a perforation in the kevlar group. All techniques of triple
      gloving were found to be superior to double gloving. There was no difference
      between the techniques of triple gloving. CONCLUSION: During certain high-risk
      procedures greater protection to the surgeon can be obtained by triple gloving.
      The use of cut-resistant glove liners or triple layer latex gloving is superior
      to double layer latex gloving.

PMID- 7562172
TI  - The relationship of the lingual nerve to the mandibular third molar region: an
      anatomic study.
AB  - PURPOSE: This study evaluated the relationship of the mandibular third molar to
      the lingual nerve. MATERIALS AND METHODS: An anatomic dissection of the lingual
      nerve in the third molar region was done on 20 cadavers (40 sides). RESULTS: The
      position of the nerve on one side bore no statistical relationship to the
      position of the nerve on the opposite side. The position of the lingual nerve was
      variable in both the sagittal and coronal planes. In two specimens the nerve lay
      superior to the lingual plate and in another the superior surface of the nerve
      was level with the crest of the lingual plate. CONCLUSION: These findings have
      implications for the avoidance of lingual nerve damage during surgery in the
      third molar and retromolar region of the mandible.

PMID- 7562174
TI  - Soft tissue and bony enlargement of the mandible in an infant.

PMID- 7562175
TI  - Bilateral abducens nerve palsy secondary to maxillofacial trauma: report of case
      with proposed mechanism of injury.

PMID- 7562173
TI  - The structure, biochemistry, and metabolism of osteoarthritic cartilage: a review
      of the literature.
AB  - PURPOSE: To understand the possible significance of the presence of proteases,
      cytokines, growth factors, and arachidonic acid metabolites in the osteoarthritic
      temporomandibular joint (TMJ), the pathogenesis of TMJ osteoarthritis (OA) is
      discussed, based on knowledge of structure, biochemistry and metabolism of
      osteoarthritic cartilage in general, and a classification of TMJ OA is presented.

PMID- 7562176
TI  - Merkel cell tumor: report of case.

PMID- 7562177
TI  - Alveolar soft-part sarcoma of the oral cavity: report of a case and review of the
      literature.

PMID- 7562178
TI  - Acetaminophen toxicity: report of case and review of the literature.

PMID- 7562179
TI  - Paradental cyst of the second molar: report of a bilateral case.

PMID- 7562180
TI  - Cervical subcutaneous emphysema due to oropharyngeal barotrauma.

PMID- 7562181
TI  - Recurrent melanoma of the hard palate treated by en bloc excision and
      reconstruction with an autologous palatal bone graft subjected to cryotherapy and
      a buccal mucosal flap.

PMID- 7562183
TI  - Surgical access for inferior alveolar nerve repair.

PMID- 7562182
TI  - Epithelioid hemangioma of the maxillary sinus: a case report.

PMID- 7562184
TI  - A modified geniotomy technique for obstructive sleep apnea syndrome.

PMID- 7562186
TI  - The safety of ketamine for emergency department pediatric sedation.

PMID- 7562185
TI  - Successful treatment of leiomyosarcoma of the tongue.

PMID- 7562187
TI  - Where have all our values gone?

PMID- 7562188
TI  - A protocol for the management of failed alloplastic temporomandibular joint disc
      implants.
AB  - PURPOSE: This is a retrospective evaluation of a protocol for management of
      failed alloplastic temporomandibular joint (TMJ) disc implants. PATIENTS AND
      METHODS: The criteria for implant failure were defined as any one or combination
      of the following symptoms and signs: TMJ pain, jaw hypomobility, occlusal
      changes, and radiographic evidence of bone pathology related to the implant. The
      protocol consisted of removal of the implant, aggressive joint debridement,
      recontouring of the articulating surfaces, and placement of a pedicled temporalis
      muscle/fascia flap (TF) for joint lining. Arch bars and maxillomandibular guiding
      elastics were used if extensive condylar recontouring was necessary. No attempt
      was made to reconstruct the condyle or correct occlusal abnormalities at the time
      of implant removal. All 27 patients (42 joints) treated by this protocol during
      the study period were included for evaluation. There were 24 Proplast/Teflon
      (PTI) (Vitek, Inc, Houston, TX), 11 Silastic (SI) (Dow Corning, Midland, MI), and
      7 Christensen Fossa implants (CFI) (TMJ Implants, Golden, CO) implants removed.
      RESULTS: The mean follow-up period was 38.3 months (range, 3 to 65 months). Pain
      was well controlled in 24 of 27 patients (88.9%). Preoperative and postoperative
      mean maximal incisal opening (MIO) was 32.1 mm and 39.8 mm, respectively. Two
      patients (7.4%) required a second TMJ operation for persistent pain and
      limitation of opening. To date, 7 patients (25.9%) have required a secondary
      procedure (unilateral vertical ramus osteotomy, n = 1; Le Fort I osteotomy, n =
      6) to correct occlusal prematurity on the operated side or bilateral open bite.
      The remaining patients have required no additional surgical treatment.
      CONCLUSIONS: The results of this study indicate that a proposed protocol is an
      effective means of controlling pain and improving jaw motion in patients with
      failed alloplastic TMJ disc implants.

PMID- 7562189
TI  - Reconstruction of the temporomandibular joint using a temporalis graft with or
      without simultaneous orthognathic surgery.
AB  - PURPOSE: This article reports the outcome of free temporalis fascia and muscle
      graft (TFG) reconstruction of the temporomandibular joint (TMJ) with and without
      simultaneous orthognathic surgery (SOS). MATERIALS AND METHODS: Twenty-nine
      patients (45 joints) were evaluated retrospectively. Group 1 consisted of 17
      patients (16 women 1 man) and 30 joints. Fifteen (88%) patients had sagittal
      split ramus osteotomies (SSRO); 8 (53%) of these patients also had Le Fort I
      osteotomies, and 2 patients (12%) had only Le Fort I osteotomies with TFG. Group
      2 consisted of 12 patients (15 joints) who received only TFG and no SOS. RESULTS:
      Group 1 had 9 patients (53%) with an incisal opening greater than 35 mm, 11
      joints (37%) with greater than 6 mm lateral excursive movement, and 11 patients
      (65%) were asymptomatic postoperatively. Average follow-up was 57.4 months
      (range, 23 to 69 months). Group 2 had eight patients (67%) with an incisal
      opening greater than 35 mm, six joints (40%) with greater than 6 mm lateral
      excursive movement, and seven patients (58%) were asymptomatic postoperatively.
      Average follow-up was 55.1 months (range, 48 to 64 months). CONCLUSION: TFG with
      and without SOS produced similar treatment outcomes in comparing groups 1 and 2.
      No significant differences were observed for the number of patients with an
      incisal opening > 35 mm (P = .703), lateral excursion > 6 mm (P = 1.00), and
      successful elimination of pain (P = 1.00), even though group 2 had a
      significantly greater number of patients (P < 0.01) that were operated on
      unilaterally. Combining treatment outcomes for both groups, the number of
      previous joint surgeries significantly affected success (P < .01). The presence
      of osteoarthritic changes did-not significantly affect treatment outcome (P =
      .187).

PMID- 7562191
TI  - A lateral cephalometric analysis of the adult nose.
AB  - PURPOSE: The purpose of this study was to establish a set of standard values for
      the form of the nose and its relationship to other craniofacial structures in
      young adult caucasians. SUBJECTS AND METHODS: The subjects were 50 (25 male, 25
      female) caucasian dental students who gave no history of orthodontic treatment,
      facial surgery, or facial fractures. Lateral cephalometric radiographs were used
      to determine the form of the nose and its position relative to other craniofacial
      structures. RESULTS: The men had significantly longer and straighter noses than
      the women, and their noses also projected further from the face. The dorsum of
      the nose was straight in most subjects. The vertical distances from the tip of
      the nose to the most prominent part of the upper lip, to the incisal edge of the
      maxillary central incisor, and to soft tissue pogonion were significantly greater
      in the men. There were no gender differences in the horizontal distances between
      the same points and the tip of the nose. Subnasale was significantly more
      prominent in the men. CONCLUSIONS: In general, the findings of nasal form and
      position are in agreement with previous studies. Several gender differences in
      nasal form and position were found. The standards reported should prove to be a
      useful yardstick for clinicians engaged in procedures likely to alter the form of
      the adult human face.

PMID- 7562190
TI  - Functional and morphologic alterations secondary to superior repositioning of the
      maxilla.
AB  - PURPOSE: The purpose of this investigation was to 1) compare morphological
      characteristics and functional performance of a sample of patients with vertical
      maxillary excess (VME) with controls, and to 2) examine how the patients' oral
      motor function adapts to surgery. MATERIALS AND METHODS: Fifteen female VME
      patients were compared with 26 female controls before and up to 3 years after
      maxillary intrusion surgery. Measures of skeletal morphology, mandibular range of
      motion, maximum isometric bite force, and levels of electromyogram (EMG) activity
      in some of the muscles of mastication were made on all subjects over time. One
      way analysis of variance (ANOVA) was used to compare the controls with the
      patients before and after surgery. Univariate repeated measures ANOVA was used to
      study longitudinal changes in the patients. RESULTS: Preoperatively, the patients
      possessed morphological measurements characteristic of vertical maxillary excess.
      Superior repositioning of the maxilla averaged 3.3 mm. Concurrently, most
      skeletal measures were brought closer to normal values. Masseter muscle
      mechanical advantage was significantly lower in the patients than in controls
      both before and after surgery (P < or = .05). There was no significant difference
      between patients and controls for other biomechanical measurements. Mandibular
      hypomobility was apparent at 6 weeks after surgery, but returned to control
      values within 6 to 12 months. Before surgery, the patients had maximum isometric
      bite forces significantly less than those of controls. Bite forces steadily
      increased after surgery, approaching normal values within 2 years. Before surgery
      the patients' muscle activity levels per unit of bite forces were equivalent to
      those of controls or somewhat lower. After surgery some of the patients' muscles
      had significantly lower levels of muscle activity per unit of bite force than did
      controls. CONCLUSIONS: The results of this study suggest that correction of
      vertical maxillary excess with maxillary intrusion surgery improves some
      characteristic functional deficits.

PMID- 7562192
TI  - Mobility of the osteotomy site following Le Fort I osteotomy stabilized by
      titanium plate osteosynthesis.
AB  - PURPOSE: This study analyzed whether titanium plate osteosynthesis prevents
      mobility after Le Fort I osteotomy and, if not, how long the osteotomized segment
      is mobile. PATIENTS AND METHODS: In 10 patients aged 17 to 49 years, three metal
      bone markers were inserted below and three above the osteotomy during the Le Fort
      I procedure, each set forming a triangle. The patients were examined at intervals
      until 1 year postoperatively. At each examination two sets of x-ray stereograms
      were obtained; one in rest and one with pressure applied to the anterior part of
      the maxilla. The difference in position of the maxillary segment in relation to
      the reference segment between the two sets of stereograms, ie, the mobility,
      could thus be recorded. Findings of 0.4 degrees and 0.2 mm are considered
      significant. RESULTS: Immediately after surgery mobility in the osteotomy site
      was found in 7 of the 10 patients. One year postoperatively mobility in the
      osteotomy site was still found in four patients. CONCLUSION: Titanium plate
      osteosynthesis does not prevent mobility between the osteotomy segments after Le
      Fort I osteotomies. The osteotomized segment may remain mobile at least until 12
      months after surgery. During this period the impact of the functional matrix may
      cause migration of the segment.

PMID- 7562193
TI  - Correlation of magnetic resonance imaging and surgical findings in patients with
      temporomandibular joint disorders.
AB  - PURPOSE: This study compared the magnetic resonance imaging (MRI) and surgical
      findings in patients with temporomandibular joint disorders. MATERIALS AND
      METHODS: Forty-three patients and 30 asymptomatic volunteers underwent MRI using
      the three-dimensional (3D) FISP acquisition technique. The 43 patients (43
      joints) then underwent discectomy, and the surgical and MRI findings were
      correlated. RESULTS: In 28 joints (28 patients), splits surrounded by regions of
      high-signal intensity were seen in the discs and retrodiscal tissues on MRI.
      Surgically, a tear was confirmed in 26 (93%) of these joints. Histologically,
      these areas showed severe myxomatous degeneration. Disc deformity was visualized
      by MRI in all patients and increases in signal intensity were found in some
      discs. High-signal intensities also were observed in 30 joint spaces, in which
      serous joint effusion was confirmed surgically. CONCLUSION: Pathologic
      intracapsular changes are accurately depicted by FISP-3D, and this method is
      particularly useful for diagnosing changes in the disc and retrodiscal tissues.

PMID- 7562194
TI  - The impact of interpersonal support on patient satisfaction with orthognathic
      surgery.
AB  - PURPOSE: This prospective longitudinal study examined the relationship between
      interpersonal support and patient satisfaction with orthognathic surgery.
      PATIENTS AND METHODS: Fifty-five adult patients were assessed with two
      questionnaires measuring the level of general social support they perceived
      receiving from significant others during treatment, and the level of perceived
      support specifically for their decision to undergo orthognathic surgery and the
      treatment results. RESULTS: Availability of support and satisfaction with support
      from specific members of the patient's support group were found to be related to
      satisfaction in the early postoperative period. Support of close friends for the
      patient's decision to undergo surgery was found to be associated with
      satisfaction in the early postoperative months. Further, reactions of the
      patient's support group to his or her postoperative appearance was found to be
      highly related to satisfaction in both the early and late postoperative stages.

PMID- 7562195
TI  - Neurosensory recovery following the mandibular bilateral sagittal split
      osteotomy.
AB  - PURPOSE: This prospective study evaluated the neurosensory recovery pattern of
      the inferior alveolar nerve following the bilateral sagittal split osteotomy
      (BSSO). PATIENTS AND METHODS: Forty-two consecutive patients undergoing BSSO were
      studied using five neurosensory tests: 1) static light touch, 2) moving touch
      discrimination, 3) two-point discrimination, 4) nociception, and 5)
      thermoreception. Intraoperative assessment of inferior alveolar nerve damage was
      made; other variables recorded included type of fixation, age, concomitant
      procedures, advancement vs setback, and magnitude of the movement. A subjective
      questionnaire was completed by the patient. RESULTS: The variables that affected
      neurosensory function following BSSO were degree of nerve damage and the amount
      of time elapsed following surgery. Larger myelinated fibers (A-alpha) recovered
      slower and to a lesser degree at all time intervals up to 2 years when compared
      with small myelinated and unmyelinated nerve fibers. The magnitude of nerve
      damage directly correlated with early neurosensory deficit, but equalized over
      time. CONCLUSION: The long term (6 months and greater) chance for neurosensory
      recovery is good despite intraoperative nerve manipulation. Patients seem to
      adapt and report normal neurosensory function even though objective testing
      indicates continued neurosensory deficit.

PMID- 7562196
TI  - Measurements of shaft speed while drilling through bone.
AB  - PURPOSE: This study investigated the effect of force on drill speed and measured
      the energy consumed during the drilling process. MATERIAL AND METHODS: Applied
      force, drill speed, and energy consumed were measured during drilling in bovine
      cortical bone specimens. A commercial surgical drill was fitted with a custom
      designed speedometer for measuring the rotational speed. The handpiece was
      attached to a laboratory drill press and positioned above a bone specimen mounted
      on a load cell. To apply steady loads, weights were placed on the drill platform,
      and tests were conducted for forces between 1.5 and 9.0 N and for free-running
      speeds from 20,000 to 100,000 rpm. RESULTS: The simultaneous measurements of
      speed and load for the electrically powered instrument showed that the average
      operating speed changed with the force applied: at low starting speeds, the speed
      increased slightly with force; at high starting speeds, the speed decreased with
      force by as much as 50%. The measurements of electric power showed that the total
      energy consumed generally decreased with speed and force, primarily because of
      decreased drilling time. CONCLUSION: The decrease in energy suggests that
      drilling at high speed and with a large force may be desirable because bone
      temperature is reduced.

PMID- 7562197
TI  - Effect of aging on the rat condylar fracture model evaluated by bromodeoxyuridine
      immunohistochemistry.
AB  - PURPOSE: The effect of aging on the recovery of cellular proliferative ability in
      the experimentally fractured rat condyle was studied by bromodeoxyuridine (BrdU)
      immunohistochemistry. MATERIALS AND METHODS: The experimental animals (male
      Sprague-Dawley rats; n = 33, unilateral condylar fracture and sham operation)
      were divided into three age groups: 3, 6, and 36-weeks old. The cell
      proliferation was evaluated by the BrdU labeling index (LI) in the intermediate
      cell layer of the condyle at 1, 2, 4, 6, and 8 weeks after the fracture. RESULTS:
      The cell kinetics of both condyles was affected by the temporomandibular joint
      dysfunction due to the unilateral condylar fracture. In all age groups, the
      fracture healed within 4 weeks. The LI of the nonfractured as well as fractured
      condyles decreased strikingly up to 2 weeks, and then only slightly increased at
      4 weeks after the fracture. The LIs of the fractured condyles were lower than
      those of the control throughout the experiment regardless of age. Eight weeks
      after the fracture the percentage of recovery of the LI in the fractured condyle
      (LIs of fractured condyle in the fracture group/LIs of right condyle in the sham
      group) was 45.1% in 3-week-old-animals, 21.2% in 6-week-old-animals, and 16.1% in
      36-week-old-animals. CONCLUSION: This study shows that the recovery of cell
      proliferation in the fractured condyle depends on age.

PMID- 7562198
TI  - Anatomic relationship of the genial tubercles to the dentition as determined by
      cross-sectional tomography.
AB  - PURPOSE: This study determined the anatomic location and the dimensions of the
      genial tubercles in relation to the apices of the mandibular central incisors.
      MATERIALS AND METHODS: Linear cross-sectional tomographic images were made of 41
      adult human skulls. A 2-mm-thick section was produced through each central
      incisor. The vertical distance between the apex of each central incisor and the
      level of the superior aspect of the genial tubercle was measured on the
      radiographs. Additional measurements were taken on the dry skulls to determine
      the horizontal distance between the apices of the two central incisors and the
      width and height of the genial tubercle. RESULTS: Although 5 mm is considered a
      safe zone for geniotomies, 29 of the genial tubercles (35.4%) were less than 5 mm
      from the apices of the mandibular central incisors. The distance between the
      apices of these incisors ranged from 9 mm to 15 mm. CONCLUSION: Osteotomy of the
      genial tubercles can be performed within the confines of the mandibular central
      incisors, but care must be taken to avoid the root apices.

PMID- 7562199
TI  - Surgical management of inferior alveolar nerve injuries (Part I): The case for
      early repair.

PMID- 7562200
TI  - Surgical management of inferior alveolar nerve injuries (Part II): The case for
      delayed management.

PMID- 7562201
TI  - Tuberculosis: diagnosis and treatment of resurgent disease.
AB  - PURPOSE: The incidence of tuberculosis is, once again, on the rise in this
      country after many years of decline. As advances in the therapeutic management of
      tuberculosis occur, oral and maxillofacial surgeons should be aware of the
      current treatment modalities. This article provides a comprehensive review of
      tuberculosis, because it is likely that we will be seeing more patients with this
      disease in our practices.

PMID- 7562202
TI  - Painless mandibular gingival mass.

PMID- 7562203
TI  - Benign osteoblastoma of the mandible: report of a case.

PMID- 7562204
TI  - Synchronous central giant cell lesions of the jaws: report of a case and review
      of the literature.

PMID- 7562205
TI  - Pilomatrixoma of the cheek: report of case.

PMID- 7562207
TI  - Technique for fixation of the Frost suture.

PMID- 7562206
TI  - Perforation of a nasotracheal tube with a Kirschner wire during maxillofacial
      surgery: report of case.

PMID- 7562208
TI  - Hemi-genioplasty: a technique to correct chin asymmetry.

PMID- 7562209
TI  - Managing facial dog bites.

PMID- 7562210
TI  - Satisfaction from performing dentoalveolar surgery.

PMID- 7562211
TI  - Dental impacts on daily life and satisfaction with teeth in relation to dental
      status in adults.
AB  - The aim of this study was to investigate whether older people having missing
      posterior teeth had few impacts and considered their teeth and mouth acceptable.
      The main objective was to assess the relationship between satisfaction with teeth
      and mouth, and the number, position and condition of the natural teeth. The
      sample was an employed unrepresentative population most of whom were in daily
      contact with the public. There was a very poor association between reported
      satisfaction with teeth and the number of standing teeth. There was little
      difference in satisfaction with dental and mouth status and the number of
      functional posterior occluding pairs (POPs). Satisfaction with the number and
      position of the functional POPs was not statistically significantly different in
      those with more or less than four POPs. However, there was slightly more
      satisfaction with teeth in the group with more than four POPs. Overall, those
      with more molar and premolar pairs were most satisfied with their teeth.

PMID- 7562213
TI  - Lifetime prediction of dental materials--an engineering approach.

PMID- 7562212
TI  - Treatment of exposed implant threads using a synthetic bone graft.
AB  - The aim of this study was to evaluate clinically and histologically the use of a
      synthetic bone graft (Ionogran) alone and in combination with guided bone
      regeneration (GBR) to facilitate bone regeneration and augmentation around
      exposed implant threads. Five male Beagle dogs were used in this investigation.
      Prior to the study all 3rd and 4th premolars were extracted. After 3 months, a
      flap was elevated and two Branemark implants were inserted in each quadrant in
      such a way that two-three threads remained exposed over the alveolar bone. On the
      control sites the synthetic bone graft was then placed around the exposed threads
      and the flaps were repositioned and sutured. On the test sites, the same
      procedure was performed, but an expanded polytetrafluoroethylene barrier was
      placed to cover the bone graft and implants. Three months after implant
      placement, the barriers on the test sites were removed, healing abutments were
      inserted on all implants, and a thrice weekly plaque control regime was
      initiated. The following clinical parameters were measured at 1, 2, and 3 months:
      Plaque Index, Gingival Index, Probing Depth and Clinical Attachment Level. Three
      months after abutment connection the animals were killed and specimens were
      obtained for histological evaluation. Clinical parameters revealed a significant
      improvement on the experimental sites compared to control sites during the 3
      month loading phase. Histological analyses, however, could not determine a
      difference in the nature of the implant/tissue interphase between experimental
      and control sites.

PMID- 7562214
TI  - The bond strength of polymers and metal surfaces using the 'silicoater'
      technique.
AB  - The silicoater technique, or silicoating, is a chemical bond system (makes
      mechanical retentions unnecessary) which prevents the rising of a gap in the
      margin area between resin and metal. This procedure solves the problems of
      fracture and detachment of the veneer or its discolourization. The purpose of
      this investigation was to find out the values of the bond strength achieved by
      using the silicoater technique on Ag-Pd alloy with smooth surface and with
      mechanical retentions on the surface. Ninety specimens were divided into groups,
      subjected to water storage and thermocycling. The values of the bond strength
      were investigated in combination with this technique with Ag-Pd alloy and three
      veneer materials. The silicoater technique gave the best results in combination
      with Dentacolor XS veneer material and mechanical retentions on the surface of
      the dental alloy.

PMID- 7562215
TI  - Studies on adaptation to complete dentures. Part I: Oral and manual motor
      ability.
AB  - The assessment of an edentate patient's ability to adapt to new dentures is still
      a problem in prosthetic treatment. In this study the oral and manual motor
      abilities were compared with a patient's ability to adapt in 60 experienced
      denture wearers who had new dentures inserted 2-3 weeks before the experiment. To
      assess the oral muscular co-ordination ability a modification of the muscular
      ability (MA) test was used. To determine the manual motor ability a 'pinhole
      board' test and a 'margin-cutting' test were employed. The degree of adaptation
      to the new dentures was assessed by a questionnaire. The results show that a
      patient's age only roughly indicates the capability of adaptation. In contrast to
      the manual motor ability, the oral motor ability seems to correlate to the
      patient's adaptation to new dentures (r = 0.55). The manual motor ability was
      clearly more strongly (r = 0.61) age-related than the oral motor ability (r =
      0.33). The permanent altered oral perception through denture wearing and a
      training effect by the permanent challenge of intra-oral denture management are
      discussed.

PMID- 7562217
TI  - Experimental occlusal interferences. Part I. A review.
AB  - This review shows that experimental occlusal interferences (prematurities) may
      cause changes in the myoelectric contraction patterns of the human jaw muscles,
      and changes in the translatory motion patterns of the human mandible. However, it
      has not been unequivocally established that the observed changes have specific
      long-term detrimental effects. On the other hand, it is apparent that
      experimental occlusal interferences are associated with short-term clinical
      symptoms and signs, such as jaw muscle fatigue and pains, headaches, pains and
      clickings in the temporomandibular joints. This review suggests that new
      paradigms involving experimental occlusal interferences should be introduced.

PMID- 7562216
TI  - Some physical and mechanical properties of shellac dental baseplate material.
AB  - The historical and general use of shellac is discussed and its particular value
      in dentistry outlined. The effects of variations in the mica and aluminium
      content of shellac are evaluated. Measurements of elastic modulus, modulus of
      rupture and glass transition temperature are reported.

PMID- 7562218
TI  - Experimental occlusal interferences. Part II. Masseteric EMG responses to an
      intercuspal interference.
AB  - In 12 subjects, a rigid unilateral intercuspal interference (minimum mean height
      of 0.24 mm) was placed on either the right or left mandibular second premolar and
      first molar (sagittal physiological equilibrium point of the hemimandibular
      dental arch). During brisk and forceful clenching on the interference, bipolar
      surface electromyograms were obtained from the right and left masseter muscles.
      On the side opposite the interference, myoelectric clenching activity was
      significantly reduced. Correlation analyses showed that the interference elicited
      a non-linear (complex) co-ordination of the amplitude, but not the duration, of
      bilateral masseteric clenching activity, i.e. frequently there was significant
      motor facilitation on the side of the interference, and significant motor
      inhibition on the side opposite the interference. Theoretical considerations
      predicted that brief clenching on the interference would easily lead to frontal
      plane rotatory motions of the mandible which, indeed, occurred clinically.

PMID- 7562219
TI  - Modified polyalkenoate (glass-ionomer) cement--a study.
AB  - Conventional glass-ionomer cements with varying amounts (5-15%) of borax
      (Na2B4O7.10H2O) as modifier were prepared. These mixtures were spatulated with an
      aqueous solution of polyacrylic acid with a powder to liquid (P/L) ratio of
      1.5:1. Properties such as working time, setting time, compressive strength,
      diametral tensile strength, solubility and fluoride release of these cements were
      determined. It was observed that the working time and setting time of the
      resultant cements shortened with the addition of borax. Certain physical
      properties such as compressive and diametral tensile strength, solubility and
      disintegration of these glass-ionomer cements deteriorated with borax addition
      but fluoride release from them was unaffected.

PMID- 7562220
TI  - An overview of common bleeding disorders.
AB  - Hemophilia and von Willebrand disease are the most common bleeding disorders.
      Management of these disorders can be challenging for the patient and healthcare
      provider. This article will review the history, diagnosis, and treatment of
      Hemophilia A, Hemophilia B, and von Willebrand disease.

PMID- 7562221
TI  - Tocolytic therapy for the prevention of preterm labor.
AB  - The focus on treatment for preterm labor lies in risk screening, assessment,
      patient education, and the use of various tocolytic drug regimens. In years past,
      preterm labor patients were treated in the hospital with IV tocolytic drug
      therapies. However, patients can now receive oral subcutaneous tocolytics while
      remaining in their own homes. Modern technology allows for some women to be
      monitored daily for changes in uterine contraction activity without
      hospitalization. Nurses play an integral role in providing home care and
      education to these patients who comply with lifestyle changes to prolong the
      pregnancy toward term gestation.

PMID- 7562222
TI  - The evolving changes in healthcare reform. Keynote speech given at the 1994
      National Academy of the Intravenous Nurses Society in Atlanta, Georgia.
AB  - This article explores three major health reform questions: (1) Why do we need to
      reform a system that provides cutting-edge healthcare? (2) What are the
      consequences of inaction? (3) Why is it so difficult to carry out a reform that
      has the support of most Americans? Based on the answers to these three questions,
      the article offers a two-prong reform alternative. First, seek a national
      consensus on why we disagree on healthcare. Second, let the states experiment
      with several promising and competing reform plans before committing to a national
      level reform.

PMID- 7562223
TI  - The management of the difficult peripherally inserted central venous catheter
      line removal.
AB  - Difficulty with removing peripherally inserted central catheters is being
      encountered with increasing frequency. The most common cause of this phenomenon
      is venous spasm. Although gentle traction may overcome mild spasm, aggressive
      pulling is contraindicated. Methods and maneuvers to alleviate spasm are
      discussed, the simplest of which is to attempt catheter removal again after a
      short (20 to 30 minutes) or intermediate (12 to 24 hours) length of time, at
      which time spasm may have spontaneously abated.

PMID- 7562224
TI  - Peripherally inserted central catheters: resistance to removal: a rare
      complication.
AB  - Peripherally inserted central catheters that resist removal occur in 8 of 829
      catheters (0.965%). Several causes may be responsible as the reason for this
      phenomenon, such as infectious process, fibrin formation, and endothelial
      thrombosis. This article describes venospasm as confirmed by ultrasound as the
      cause. Removal in all but one catheter was completed in approximately 1 hour with
      gentle pulling, taped tension, and warm soaks for 20 minutes. Tourniquet
      application and gentle traction were employed. If unsuccessful, the tourniquet
      was removed and warm soaks reapplied. One catheter did not respond to this
      recommended treatment and was stuck for six days. Treatment of catheter embolus
      is outlined should the catheter be inadvertently broken during the removal
      process.

PMID- 7562225
TI  - Central venous catheter infection rates in an acute care hospital.
AB  - When questions arose in the spring of 1990 concerning central venous catheter
      infections at a 414-bed, midwestern hospital, it was found that no hospital-wide
      prospective study of this problem had ever been completed. A descriptive,
      prospective study was conducted over 6 months, from October 1990 to April 1991,
      to determine the rate of infection associated with short-term central venous
      catheters at the study hospital. Additional research questions sought to examine
      the influence of certain risk factors on central venous catheter infection rates.
      Observation of central venous catheter sites was done every other day. Distal
      catheter segments were cultured by the semi-quantitative roll-plate method and by
      broth culture. Blood cultures were drawn at the physicians' clinical discretion.
      Organisms were fully speciated when clinically indicated. The investigators
      examined 448 catheters in 209 patients. One hundred thirty-nine catheters were
      not cultured because of random human error or coroner's requirements. In the
      remaining 309 catheters in 158 patients, a total of 5 clinical line infections
      was found. The infection rates were 1.6% for catheters, 2.8 infections per 1000
      catheter days, and 3.2% per patient. Correlation of infection with risk factors
      was not possible because of the small number of infections. The clinical line
      infection rates found in this study compare favorably with other rates reported
      in the literature. Although the presence of any exceptional problem with central
      line infections at the hospital was not supported by this study, the number of
      lines placed during the study emphasizes the importance of high-quality central
      venous catheter placement and maintenance technique throughout the institution.

PMID- 7562226
TI  - Transcutaneous electrical nerve stimulator for procedural pain associated with
      intravenous needlesticks.
AB  - Venipuncture continues to be considered a painful and unpleasant experience for
      those receiving medical treatment. A prospective study investigating whether the
      application of a transcutaneous electrical nerve stimulator (TENS) decreases the
      complaints of pain and unpleasantness with i.v. needle insertion was conducted
      using a group of 71 subjects who were double-blinded and randomized to one of
      three groups: TENS, placebo-TENS, and control. This article gives an overview of
      this research and describes its findings.

PMID- 7562227
TI  - [Postoperative MRI findings after cholesteatoma surgery].
AB  - This study was designed to show MRI findings of postoperative middle ear
      pathologies and to discuss the usefulness of Gadolinium-enhanced MRI in
      evaluating the postoperative state of cholesteatoma. Thirty-eight ears which
      underwent intact canal wall tympanoplasty for cholesteatoma were examined.
      Recurrent cholesteatoma was detected as an iso-intensity area on T1-weighted
      images with negative enhancement. Notably, residual cholesteatoma were generally
      depicted as a round iso-intensity area with negative enhancement. Residual
      cholesteatoma less than 5mm in diameter were, however, not generally detectable
      with our MRI scanner. Granulation tissue can be separated from cholesteatoma as
      an area with positive enhancement. Cholesterol granuloma shows a characteristic
      high signal pattern on both T1 and T2-weighted images. Hypovascular fibrous
      tissue and fluid collection may be depicted as a pattern similar to that of
      cholesteatoma. However, the signal is usually more homogeneous than that of
      cholesteatoma. We conclude that Gadolinium-enhanced MRI is useful for detecting
      postoperative cholesteatoma and avoiding unnecessary second-look operations after
      cholesteatoma surgery, by the canal-up procedure.

PMID- 7562228
TI  - [Relationship between birch pollen allergy and oral and pharyngeal
      hypersensitivity to fruit].
AB  - We evaluated the relationship between birch pollen allergy and oral and
      pharyngeal hypersensitivities to certain fruits. 1. Of 171 birch pollen CAP
      positive (score > or = 2) patients, twenty two (13%) were revealed to be
      hypersensitive to apples, eleven (6%) to be hypersensitive to peaches, both rates
      being higher than those found in patients with other CAP positive reactions
      (orchard grass pollen CAP, mugwort pollen CAP or Dermatophagoides pteronyssius
      CAP positive). 2. Among the birch pollen CAP positive patients, the higher the
      CAP score for birch pollen, the higher the prevalences of hypersensitivity to
      apples and peaches were found to be. 3. Of 171 birch pollen CAP positive
      patients, six (3.5%) were revealed to be hypersensitive to kiwi fruit. Of 253
      patients with other CAP positive reactions, three (1%) were revealed to be
      hypersensitive to kiwi fruit.

PMID- 7562229
TI  - [A case of palatal polymorphous low grade adenocarcinoma].
AB  - We present a 58-year-old male patient with bilateral cheek swelling and an
      extraorally protruding tumor who has had deaf mutism since birth. He underwent
      surgery of the right hard palate 11 years ago. Five years later biopsy was
      performed for a recurrent lesion diagnosed as pleomorphic adenoma. He refused
      additional treatment and the size of the tumor subsequently increased slowly. As
      rapid tumor-growth had been observed since autumn of 1992, he was referred to
      Tokyo University Hospital. We took meticulous care of this deaf-mute patient,
      especially from the psychological aspect, which caused him to place great
      reliance upon us. We performed bilateral maxillectomy with partial resection of
      the right cheek skin and reconstructed his face and palate successfully using
      both latissmus dorsi and serratus anterior musculocutaneous free flaps with a
      rib. Histopathological diagnosis of the tumor was polymorphous low grade
      adenocarcinoma, which was registered as a definite entity in the WHO
      Classification in 1991. There was no evidence of local recurrence or metastasis
      one year postoperatively.

PMID- 7562231
TI  - [Detection of a mutation in mitochondrial DNA in a family with sensorineural
      deafness and diabetes mellitus as the predominant clinical features].
AB  - An A to G transition at nucleotide 3,243 in the tRNA(Leu(UUR)) gene of
      mitochondrial DNA (mtDNA) has been suggested to be the disease-related mutation
      for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke
      like episodes). Recently, the same mutation has also been found in several
      pedigrees with maternally inherited diabetes mellitus and sensorineural deafness.
      We report here a family showing the association of deafness and diabetes
      mellitus, as the predominant clinical features, with this mutation. The mutation
      was detected by restriction-enzyme analysis of the relevant PCR-amplified segment
      of the mtDNA, in two generations. In this family, it is noteworthy that two
      members with the mutation had some symptoms of MELAS such as short stature,
      seizures and mental retardation and that one had no clinical symptoms though the
      mtDNA mutation was identified in his blood. The findings in this family
      demonstrate the diversity of clinical expression of the mtDNA mutation and
      suggest that a combination of sensorineural deafness and diabetes mellitus is
      only one typical presentation of the various phenotypic features caused by the
      3,243 mutation.

PMID- 7562230
TI  - [Changes in respiratory function before and after laryngectomy].
AB  - Many patients with head and neck cancer have a smoking history, and pulmonary
      complications frequently lead to post-operative death. Due to technical problems,
      spirometric pulmonary function tests are rarely performed in patients with
      laryngectomy. The purpose of this study is to evaluate respiratory function in
      patients with laryngectomy. We made a tracheal mask with a heat and moisture
      exchanging baseholder, and used it for spirometry. Eight patients with
      laryngectomy, including 5 with laryngeal cancer and 3 with hypopharyngeal cancer,
      were studied. Arterial blood gas analysis and pulmonary function measurements,
      such as VC, % VC, FEV1.0% and V25/height (V25/HT), were evaluated before and
      after laryngectomy. Statistical analysis of the data was performed with the
      Wilcoxon rank-sum test. The following results were obtained: 1) No statistically
      significant changes in arterial blood gases and FEV1.0% were found. 2) A
      statistically significant decrease in VC was found after total laryngectomy (p <
      0.05). 3) A statistically significant decrease in V25/HT, which reflects small
      air way closure of the lung, was observed after total laryngectomy (p < 0.05). In
      all cases, the V25/HT value was below normal limits. We concluded that the
      decrease in VC was caused by a decrease in dead space in the upper airway, and
      that V25/HT may be a good parameter for evaluation of pulmonary function after
      laryngectomy.

PMID- 7562232
TI  - [Vestibular function in cochlear implants--prognostic factors and postoperative
      damage].
AB  - Eighteen patients with a 22-channel cochlear implant were evaluated both pre- and
      postoperatively with vestibular function tests; caloric test and body balance
      test using stabilometry. Preoperative promontory stimulation results and
      postoperative psychophysical factors of the cochlear implant showed no
      correlation with the preoperative vestibular function test results. The results
      of speech perception tests were not affected by the degree of residual vestibular
      function in any of the patients. However, for patients with deafness for a period
      of 10 to 20 years, the degree of the residual vestibular function estimated by
      the caloric test showed a correlation with the results of speech perception
      tests, significantly in the consonant recognition score. The results, not of
      length or the Rombberg ratio, but rather of the area of body sway, showed a
      correlation with the results of speech perception tests; consonant recognition,
      in patients with a short duration of deafness. Therefore preoperative vestibular
      function results may be useful as a predictive factor in postoperative speech
      perception; consonant recognition, for patients with a short duration of
      deafness. Reduced results of caloric testing after surgery were found in one of
      11 patients (9%) with residual vestibular function. The occurrence of vertigo
      immediately after surgery was observed in 5 of 18 patients (28%), but this
      symptom was transient. No change in stabilometry results, pre-versus post
      operatively, was observed. Thus, vestibular damage after surgery was considered
      to be minimal.

PMID- 7562233
TI  - [A case of vascular leiomyoma in the larynx].
AB  - We report a recently encountered case of vascular leiomyoma in the larynx. The
      patient was a 76-year-old man with a chief complaint of hoarseness. Laryngoscopy
      revealed a bean-sized, reddish tumor with a smooth surface, suspended from the
      right vocal cord toward the subglottis. Its border was clear on MR imaging.
      Tracheotomy was performed under local anesthesia, and laryngomicrosurgery was
      then carried out under general anesthesia. The tumor was encapsulated and could
      be completely resected. Histological study indicated smooth muscule cell
      proliferation, especially around capillaries, and the tumor was diagnosed as a
      vascular leiomyoma. Our extensive survey of the literature revealed 20 reports of
      benign myogenic tumor of the larynx (9 cases of simple leiomyoma, 10 of vascular
      leiomyoma, and 1 of leiomyoblastoma), many of which occurred in the middle and
      advanced years. The patients consisted of 15 men and 5 women, including 9 male
      vascular leiomyoma patients of middle or advanced age. The site of occurrence was
      supraglottic in 12, glottic in 4 and subglottic in 4; no relation was observed
      with the histological picture, however. Treatment was surgical, and some cases
      also required tracheotomy depending on the site of occurrence and morphology.

PMID- 7562234
TI  - [Whole mouth gustatory test (Part 2)--Effect of aging, gender and smoking on the
      taste threshold].
AB  - The whole mouth test method was employed for examining changes in gustatory
      senses due to aging. Participants were 314 male and 356 female healthy volunteers
      not complaining of taste disorders. Simultaneously, the effects of smoking were
      examined, comparing 71 male smokers to 142 male non-smokers, ranging from 20 to
      more than 60 years of age. A multiple comparison procedure (Tukey-Kramer) was
      applied to age groups, revealing a significant increase in the threshold with
      age; high threshold values were observed in the "70s and older" group in
      comparison to the younger group for all tastes other than the sweet taste.
      Concerning the differences between males and females, the gustatory thresholds of
      males were found to be higher than those of females for some in the "20s and
      older" group and for all tastes other than the sweet taste, whereas the
      thresholds of males were lower than those of females for all taste qualities in
      the late teen group. As to male subjects in whom the effects of smoking could be
      studied, smokers in their 20s demonstrated a slight rise in the threshold only
      for the bitter taste.

PMID- 7562235
TI  - [Therapeutic efficacy of zinc picolinate in patients with taste disorders].
AB  - We studied the therapeutic efficacy of zinc picolinate in patients with zinc
      deficient and idiopathic taste disorders. Efficacy was assessed in a double-blind
      study. The following findings were obtained: 1. There was a significant
      difference between the zinc picolinate and placebo groups in the grade of
      improvement shown by the filter-paper disk method. 2. There was a significant
      difference between the zinc picolinate and placebo groups in the serum zinc
      concentration. 3. There was no significant difference between the two groups in
      the degree of total subjective recovery or the grade of improvement, as shown by
      in the whole mouth method. 4. We conclude that the administration of zinc
      picolinate is effective for patients with zinc-deficient and idiopathic taste
      disorders.

PMID- 7562236
TI  - [Influence of aging on electrogustometric threshold].
AB  - Electrogustometric testing was carried out, with one researcher examining the
      electrogustometric threshold at three sites, in 461 normal cases, by TR-06 (Rion
      Co.), over a wide range. A multiple comparison procedure (Tukey-Kramer) was
      applied to age groups, revealing a significant increase in the threshold with
      advancing age; high threshold values were observed in the "60s and older" group
      for the chorda tympani nerve area (tongue tip) and the glossopharyngeal nerve
      area (tongue base), and in the "70s and older" group for the superficial greater
      petrosal nerve area (soft palate). As to the gender difference in women, a
      significant drop was observed in the late teens whereas a low tendency in all
      sites tested was not statistically, significant in other age groups. Differences
      between the right and the left sides were seen in most cases but were within 6dB.
      As to site differences, the soft palate threshold was higher than those of the
      tongue tip and the tongue base in all age groups. A significant decrease in the
      threshold of the tongue tip, as compared to the tongue base, was observed for
      those in their late teens, whereas minimal differences were noted in the other
      age groups and at other sites. The soft palate threshold was significantly
      reduced in smokers in their 30s and 40s as compared with non-smokers.

PMID- 7562237
TI  - [Temporal and spatial pattern analysis of pharyngeal swallowing in patients with
      abnormal sensation in the throat].
AB  - There are many patients who complain of abnormal sensations, such as an
      obstructive sensation, foreign body sensation, difficulty in swallowing, etc., in
      the throat, which do not have an obvious cause. The causes of such unpleasant
      symptoms have not been adequately investigated. As one of the potential factors
      in volved in abnormal sensations in the throat, we considered the existence of
      subclinical dysphagia. We then performed videofluoroscopic analysis in patients
      with an abnormal sensation in the throat to examine whether or not there were
      functional disorders in swallowing. Videofluoroscopy was performed in 42
      subjects, 30 patients with abnormal sensation in the throat and 12 volunteers
      without swallowing problems. We devised a temporal and spatial analysis system of
      swallowing using personal computer technology. Videofluoroscopic swallowing
      sequences during spoon feeding (3-5ml) and drinking from a cup (15-20ml) of
      liquid barium, were analyzed. The results suggest that two temporal measurements
      of swallow from videofluoroscopic studies are appropriate for parameter of
      subclinical dysphagia: the time it takes the bolus to move through pharynx from
      the point at which the bolus head passes the tongue base until the bolus head
      extends caudally beyond the piriform sinus while feeding from a spoon (S2), and
      the time it takes the bolus to move through the upper esophagus from the point at
      which the bolus head passes the bottom of the piriform sinus until the bolus tail
      passes the same point while drinking from a cup (C1). Then, we selected C1 and S2
      for variables and detect the patients who have subclinical dysphagia with cluster
      analysis. Forty-two subjects were divided into two groups: those composed of 14
      patients (cluster 1), and those composed of 16 patients and 12 controls (cluster
      2). We thought 14 patients in cluster 1 would have subclinical dysphagia for the
      cause of abnormal sensation in the throat. Temporal and spatial analysis revealed
      three forms of pharyngeal swallow in cluster 1. In 6 patients, the bolus stall in
      the valleculae prior to the onset of the pharyngeal swallow. In other 6 patients,
      the bolus stall in the piriform sinus before swallowing reflex. In the other 2
      patients, the bolus moved smoothly but slowly without delay in pharynx. Our
      results indicate that a delayed swallowing reflex is the main functional finding
      in videofluoroscopy in patients with subclinical dysphagia contributing to an
      abnormal sensatin in the throat.

PMID- 7562238
TI  - Use of pyruvate oxidase to overcome pyruvate inhibition during the lactate to
      pyruvate reaction for assaying lactate dehydrogenase in serum.
AB  - Automated assays of lactate dehydrogenase (LD) in serum are based on measuring
      the rate of NADH produced in a reverse LD reaction using lactate and NAD. The
      observed nonlinearity of LD reaction used in earlier assays performed in
      phosphate buffers has generally been attributed to the formation of a ternary
      complex of NAD, pyruvate, and phosphate. this is not satisfactory to explain the
      course of assay reaction carried out in organic buffers. Investigation of the
      possible causes of nonlinearity during the course of the reverse LD reaction
      during LD assays performed in Tris or other organic buffers indicated that
      inhibition of LD activity by pyruvate may be chiefly responsible for the observed
      effects, especially in serum exhibiting abnormally high LD enzyme activity. Most
      of the LD activity in serum was inhibited by 5 mMoles/L pyruvate. By contrast,
      the LD isoenzyme activities were inhibited partially at 0.5 mMole/L pyruvate, LD1
      being the most and LD4 the least susceptible. In assays of serum samples with
      abnormally high LD and PYR concentration using LD reagent containing Tris buffer,
      pH 9.3, the inclusion of a bacterial pyruvate oxidase (PO) enabled the removal of
      pyruvate accumulating in situ, making it possible to assay LD activity in the
      absence of inhibitory concentration of pyruvate. The inclusion of 10 U/L of PO in
      our routine LD reagent was sufficient to overcome pyruvate inhibition, thus
      permitting the assay of serum exhibiting high LD activity, hence the extension of
      the upper limits of linearity of LD assay without compromising assay performance.

PMID- 7562239
TI  - Urinary gonadotropin peptide: collection of specimens and cutoff levels.
AB  - A low-molecular-weight form of human chorionic gonadotropin (hCG), urinary
      gonadotropin peptide (UGP), has been isolated from the urine of pregnant women
      and of patients with cancer, mainly of gynecological origin. The clinical value
      of UGP measurement in gynecological diseases is under investigation but a
      preliminary study is necessary in order to ascertain whether there is a circadian
      rhythm in UGP production, to clarify the best way to express the results, and to
      establish the cutoff and decisional values. In our work we demonstrated a
      significant correlation between the UGP output and the UGP excretion normalized
      for urinary creatinine. A very significant agreement was even found in 24-hr
      urine collections and UGP concentration of a single morning specimen from the
      same patients. No evident circadian rhythm was found, although some patients
      presented morning levels of UGP higher than in other collections. UGP
      postmenopausal levels were higher than premenopausal. The cutoff level, adopting
      the 95.0 percentile, was 200 pmol/mol creatinine.

PMID- 7562240
TI  - Bioassay vs. immunoassay for quantification of interleukin-6 in biological
      fluids.
AB  - As several possible prognostic and therapeutic applications of interleukin-6 are
      currently under trial, the available methods for its quantification in biological
      fluids should be evaluated. In this report, the 7TD1 hybridoma bioassay is
      compared to an enzyme immunoassay for the determination of interleukin-6 in serum
      and plasma of normal subjects and patients with cancer, sepsis, and systemic
      lupus erythematosus, as well as in malignant pleural effusions and culture
      supernatants. The results show a good correlation between the two methods in all
      cases. Mean values of the examined groups were statistically different between
      the assays only in the case of septic patients. This may be attributed either to
      the influence of other molecules on the assays or to the nonlinearity of the dose
      response curves. Since immunoassays are easier to perform, it seems that they are
      more suitable for routine use, the bioassay being preferable in cases where
      increased sensitivity is required.

PMID- 7562241
TI  - Analysis of whole-blood cyclosporin G by liquid chromatography in renal
      transplant recipients.
AB  - Cyclosporin G (CsG) is less nephrotoxic than Cyclosporin A (CsA) and is
      undergoing clinical trials for use as an immunosuppressive agent after renal
      transplantation. In this study, CsG was measured by a rapid high-performance
      liquid chromatography (HPLC) technique in blood samples (n = 107) received from
      renal transplant recipients. The HPLC assay proved to be analytically suitable in
      that it was sensitive, linear, and precise and had high recovery (102%). However,
      interference was observed from some potentially co-administered drugs such as
      calcitriol, ferrous sulfate, hydrazaline, and minoxidil. The HPLC assay for CsG
      correlated well with a FPIA (Abbott TDx), FPIA = 0.964 (HPLC) + 33.59, r =
      0.9819, Sy/x = 36.66 for patients receiving a low dose of CsG (5 mg/kg/day) and a
      high dose (10 mg/kg/day). Furthermore, the HPLC technique was capable of
      measuring predictable CsG concentrations when the drug was tapered to lower doses
      at various stages of the 16 week clinical trial. The HPLC for CsG has the further
      advantage that the same system and mobile phase can be used to measure CsA while
      using CsC as the interval standard.

PMID- 7562242
TI  - PSA immunoreactivity detected in LNCaP cell medium, breast tumor cytosol, and
      female serum.
AB  - We made an effort to identify a reliable source for obtaining large quantities of
      both free (PSA) and PSA-ACT complex for the preparation of the calibrator for the
      PSA assay. Using size exclusion chromatography, we found both free PSA and PSA
      ACT complex in the conditioned cell medium of the LNCaP cell line, which was
      derived from a human metastatic adenocarcinoma of the prostate. An assay specific
      for PSA-ACT reacted only with the PSA-ACT complex from cells grown in serum-free
      medium, and not with the complex from the cell medium grown in 10% calf serum. We
      also found both free PSA and PSA-ACT complex in 15% of cytosols prepared from
      breast tumor tissues; the cytosol PSA concentrations ranged from 0.1 to 110
      ng/ml. No correlation was found between cytosol PSA and concentrations of
      estrogen receptor, progestin receptor, epidermal growth factor receptor,
      cathepsin D, or the ectodomain of c-erbB-2 protein. Based on chromatographic
      characterizations and the slope of their dose-response curves, it appears that
      both free PSA and PSA-ACT complex found in the cytosols are similar to PSA
      complex from the cell medium and the serum of prostate cancer patients. Ectopic
      PSA was also detected in pooled sera from patients with breast, ovarian,
      pancreatic, and colon carcinoma. The PSA concentrations in these serum pools
      increased with the level of their dominant tumor marker. In any event, the LNCaP
      cell medium appears to be a reliable source for obtaining both free and ACT
      complexed PSA of human tumor origin for the preparation of PSA assay calibrators.

PMID- 7562243
TI  - Development of a microplate ELISA for free PSA and PSA-ACT complex in serum.
AB  - An ELISA on microplate was established for the total serum PSA. We selected the
      monoclonal antibody for the assay from commercial sources making certain that it
      reacted with both free PSA and PSA-alpha 1-antichymotrypsin (PSA-ACT) complex
      from human serum with similar affinity (so-called "equimolar"). We also chose a
      test format with polyclonal anti-PSA antibodies coated on the well and monoclonal
      anti-PSA antibodies for quantification to gain higher test sensitivity. Two
      different sample volumes from each specimen, 5 and 50 microliters, were used for
      the assay in order not only to further increase test sensitivity and improve
      precision at both low and highly elevated PSA concentrations, but also to widen
      the assay concentration range (0-500 ng total PSA per ml). Using two sample
      volumes also reduces any hook effect and shortens the turn-around time because
      repeated determinations are usually required when specimens contain highly
      elevated PSA concentrations. The use of pooled sera containing approximately 95%
      PSA-ACT complex and 5% free PSA as a calibrator allows for a close matching of
      the calibrator with serum specimens in immunoreactivity and PSA composition.
      Moreover, our assay shows no hook effect up to 15,000 ng/ml. The within-day
      precision (% CV) in the critical concentration range of 4-12 ng/mL is
      approximately 5%. The PSA values obtained from this assay correlate well with
      that of the Hybritech kit (gamma = 0.998, slope equals to 1.033), indicating that
      this kit can replace the Hybritech Tandem E PSA kit for serum PSA determination
      in clinical laboratories.

PMID- 7562244
TI  - Generation, purification, and characterization of a recombinant source of human
      prostate-specific antigen.
AB  - Human prostate-specific antigen (PSA), a 33- to 34-kDa serine proteinase with
      extensive homology to glandular kallikrein, is a single-chain glycoprotein that
      contains 7% carbohydrate. The presence of PSA in the serum of patients with
      prostatic cancer is widely employed as a marker of disease status. PSA has also
      been thought of as a possible target for use in active specific immunotherapy
      protocols. To date, the source of PSA employed has been seminal fluid from
      different individuals; this has raised concerns about differences among PSA
      batches for standardization of assays. This report is the first description of
      the production and the purification of a recombinant source of PSA using a
      baculovirus expression system. A baculovirus recombinant of the cDNA encoding the
      full length PSA was expressed in insect cells yielding two major immunoreactive
      products of 31 and 29 kDa. The latter size conforms to the molecular weight of a
      core preprotein deduced from the sequence of the cDNA insert. The larger protein
      represents the N-linked glycosylated form of the preprotein. Western blot
      analysis showed that both the glycosylated and aglycosylated forms of PSA reacted
      with a polyclonal and two different monoclonal antibodies specific for PSA. bV
      PSA, like commercially available PSA, showed also low-molecular-weight
      immunoreactive products when culture supernatants were concentrated or taken
      through steps of purification. bV-PSA was purified to a final product consisting
      of a major 29-kDa protein and a minor 31-kDa protein.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7562245
TI  - PCR in clinical diagnosis.

PMID- 7562246
TI  - Microsatellite instability and hereditary non-polyposis colon cancer.

PMID- 7562247
TI  - Recent insights into the mechanisms of iatrogenic arteriosclerosis.

PMID- 7562248
TI  - Ductal carcinoma in situ: assessment of necrosis and nuclear morphology and their
      association with biological markers.
AB  - One hundred and five cases of pure ductal carcinoma in situ (DCIS) seen in the
      Guy's Hospital breast unit between 1975 and 1991 were reviewed. The presence and
      extent of necrosis and the degree of cytonuclear differentiation were assessed
      and the expression of p53 protein, cerbB2 protein, progesterone receptor, and a
      proliferation antigen KiS1, all factors reported to be of prognostic significance
      in invasive ductal carcinoma, was evaluated using immunohistochemical methods. A
      strong correlation was seen between the presence and extent of necrosis and the
      degree of cytonuclear differentiation and between both these morphological
      criteria and the biological markers as well as between the individual markers.
      The presence of extensive necrosis was associated with lack of cytonuclear
      differentiation and both were associated with a high proliferation rate, the
      presence of cerbB2 and p53 protein, and the absence of progesterone receptors. In
      cases with little or no necrosis, there was good nuclear differentiation and a
      strong correlation with the presence of progesterone receptor, absence of cerbB2
      and p53 protein, and a low rate of proliferation.

PMID- 7562250
TI  - Correlation of numerical chromosome 11 and 17 imbalance with metastasis of
      primary breast cancer to lymph nodes.
AB  - Abnormalities of chromosomes 11 and 17 have been widely reported in invasive
      carcinoma of the breast. Interphase cytogenetics using pericentromeric repeat
      probes allows the evaluation of numerical chromosomal aberrations in tumour cell
      populations. We have developed a method for interphase cytogenetics on fine
      needle aspirates taken from breast tumours and have applied it to the analysis of
      chromosomes 11 and 17 in 49 cases of invasive adenocarcinoma. Frequency
      distributions of signal number were generated for each case and no correlation
      was found between modal signal number and tumour size at presentation, nodal
      status or tumour differentiation. In 14 cases, two copies of each of chromosomes
      11 and 17 were present, and in 14, the number of chromosomes 11 and 17 were equal
      but abnormal. In 14 cases, the chromosome 11 number was greater than chromosome
      17 and in 7 cases, the chromosome 17 number was greater than chromosome 11.
      Chromosome inequality correlated with the presence of lymph node metastases or
      disseminated disease at presentation and the absence of in situ carcinoma. There
      was no relationship with the presence of vascular invasion. These data suggest
      that numerical chromosome 11 and 17 imbalance may indicate the ability of breast
      cancers to metastasize rather than invade vessels. The pattern of numerical
      chromosome abnormality described may define a subgroup of tumours with a greater
      tendency for metastasis.

PMID- 7562251
TI  - p53 gene alterations in special types of breast carcinoma: a molecular and
      immunohistochemical study in archival material.
AB  - The p53 locus on the short arm of chromosome 17 at 17p13.1 was examined for small
      genomic deletions and mutations in 23 formalin-fixed, paraffin-embedded cases of
      special types of breast carcinoma (six medullary, seven apocrine, five
      differentiated tubular, and five papillary). p53 mutations in the evolutionarily
      conserved exons 5-9 were detected in 11 cases (four apocrine, two papillary, two
      medullary, and three differentiated tubular), using the novel non-radioactive PCR
      based Hydrolink mutation detection enhancement (MDE) method, and confirmed by
      direct sequencing of the PCR products. Missense mutations causing amino acid
      substitutions were evenly distributed among exons. One case of apocrine carcinoma
      showed a polymorphism at codon 213 (CGA-->CGG). Twelve out of 23 cases were found
      to express a strong nuclear signal against CM-1 and DO-7, two anti-p53-specific
      antibodies. Small genomic deletions in the vicinity of the p53 locus were
      detected in 11 tumours (three papillary, three differentiated tubular, two
      medullary, and three apocrine carcinomas), using the multiplex PCR method. No
      statistical correlation was found between deletions at 17p13.1 and p53 mutations
      (P < 0.5). In addition, p53 mutations and immunoexpression correlated with the c
      erbB-2 gene product, an oncogenic protein that has been implicated in cell cycle
      control (P < 0.001). Our findings suggest that genomic alterations of the p53
      gene are quite common events associated with special types of breast carcinoma,
      particularly of the apocrine subtype, but the prognostic value is unlikely to be
      of clinical importance.

PMID- 7562249
TI  - The prognostic value of oncogenic antigen 519 (OA-519) expression and
      proliferative activity detected by antibody MIB-1 in node-negative breast cancer.
AB  - The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour
      proliferative activity was evaluated in a retrospective series of 118 patients
      with low-risk breast cancer. Low risk was defined as negative axillary nodes,
      tumour diameter < or = 50 mm, and no histological evidence of invasion of skin or
      deep fascia (= T1N0M0 and T2N0M0). The median follow-up time was 104 months
      (range 5-143 months). Immunohistochemical analysis of OA-519 expression was
      performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity
      was estimated using a Ki-67 equivalent monoclonal antibody (MIB-1), which is
      applicable on formalin-fixed, paraffin-embedded tissue after microwave
      pretreatment. OA-519 was expressed in about one-third of the tumours and the
      percentage of proliferating cells (the MIB-1 index) ranged between 1 and 72 per
      cent (median 17 per cent). Using multivariate Cox analysis, both the MIB-1 index
      and OA-519 expression were of independent prognostic value (2p < or = 0.01), and
      the combined immunohistological approach may therefore be useful in selecting
      patients with node-negative breast cancer who might benefit from adjuvant
      therapy.

PMID- 7562252
TI  - Apoptosis in the human liver during allograft rejection and end-stage liver
      disease.
AB  - The contribution of apoptosis (programmed cell death) to cellular damage in human
      liver disease is unknown. Using the in situ DNA end labelling method (ISEL),
      evidence was sought of programmed cell death (PCD) in liver tissue from patients
      with various liver diseases. In particular, the study aimed to determine whether
      PCD is involved in either the loss of interlobular bile ducts (vanishing bile
      duct syndrome--VBDS) or the perivenular hepatocyte drop-out, both of which are
      characteristic of irreversible graft rejection. Large numbers of apoptotic
      hepatocytes were found in perivenular areas in tissues taken from patients with
      chronic graft rejection. Significant hepatocyte apoptosis, was not seen in long
      term stable allografts, primary biliary cirrhosis, cholestasis, paracetamol
      induced fulminant hepatic failure, or fulminant hepatic failure of indeterminate
      origin (non-A, non-B, non-C hepatitis). Bile ducts rarely stained positively, but
      mononuclear cells present in the post-transplant tissues were frequently
      positive, showing nuclear or cytoplasmic staining. The presence of cytoplasmic
      staining suggested that some mononuclear cells had ingested apoptotic DNA from
      other cellular sources. PCD may thus contribute to the perivenular hepatocyte
      loss in chronic rejection. The absence of ductular epithelial cell staining
      suggests that PCD is not involved significantly in the bile duct loss of VBDS.
      Furthermore, apoptosis of mononuclear cells implies that PCD may be involved in
      regulating the inflammatory cell infiltration of graft rejection.

PMID- 7562253
TI  - Subcellular localization of pyruvate dehydrogenase dihydrolipoamide
      acetyltransferase in human intrahepatic biliary epithelial cells.
AB  - In previous histological studies, biliary epithelial cells (BEC) in the liver of
      patients with primary biliary cirrhosis (PBC), but not controls, reacted strongly
      with antibodies specific for the major autoantigen associated with PBC, the E2
      component of pyruvate dehydrogenase complex (PDC-E2). In this study we have used
      transmission electron microscopy (TEM) to document the precise subcellular
      localization of PDC-E2 in BEC. Two antibodies which recognize PDC-E2 were used:
      affinity-purified anti-PDC-E2 raised in rabbits; and human antibody from the
      serum of patients with PBC, affinity-purified against human heart PDC. The
      intracellular localization of antibody binding was determined by laser scanning
      confocal microscopy and TEM. Both antibodies bound to the inner membrane of
      mitochondria in BEC isolated from both patients with PBC and controls, but
      binding to the external aspect of the plasma membrane was observed only in BEC
      from patients with PBC. Surface antigen expression in PBC may make BEC
      immunological targets.

PMID- 7562254
TI  - The lymphoepithelial organization of the tonsil: an immunohistochemical study in
      chronic recurrent tonsillitis.
AB  - Interactions between leukocytes and crypt epithelium were extensively
      investigated in 12 cases of chronic recurrent tonsillitis, using
      immunohistochemistry and cytofluorimetric analysis of cell suspensions.
      Intraepithelial leukocytes are a mixed cell population composed of 50 per cent
      CD20-positive B lymphocytes, 40 per cent T lymphocytes with a 2.7 CD4/CD8 ratio,
      and 10 per cent CD68-positive macrophages. About 4 per cent of intraepithelial
      leukocytes are proliferating cells, as indicated by Ki-67 staining. Leukocyte
      infiltration is associated with expression on epithelial cells of the adhesion
      molecules ICAM-1 and VCAM-1. Crypt epithelium is supported by a basement membrane
      showing frequent interruptions and connected with the reticular stroma of the
      lymphoid tissue, which was stained for fibronectin, tenascin, collagen, and
      laminin. Extracellular matrix (ECM) distribution was correlated with integrin
      expression on B and T lymphocytes. It was found that the ECM was arranged
      differently in the follicles and in the extrafollicular area and that B and T
      lymphocytes exhibited different patterns of integrin expression.

PMID- 7562255
TI  - Detection of herpes simplex virus DNA in spontaneous abortions from HIV-positive
      women using non-isotopic in situ hybridization.
AB  - The purpose of this study was to determine the prevalence of Herpes simplex virus
      (HSV) endometritis in spontaneous abortions in HIV-positive women using non
      isotopic in situ hybridization (NISH). Post-abortal endometrial curettings from
      18 HIV-positive women were investigated for the presence of HSV-1 and HSV-2 DNA
      with NISH. In addition, 18 unselected post-abortal endometrial curettings in HIV
      negative women were used as controls, together with samples of normal
      proliferative and secretory endometrium. Thirteen of the 18 specimens (72 per
      cent) from the HIV-positive study group demonstrated the presence of HSV DNA,
      while 2 of the 18 HIV-negative group (11 per cent) showed a positive signal.
      Although the prevalence of HSV endometritis in the HIV-positive group was
      significantly higher than in the HIV-negative group (P < 0.05), a causal role for
      the virus in inducing the abortion remains to be determined. In addition, the
      significance of HSV endometritis with regard to the clinical management of HIV
      positive patients is as yet uncertain.

PMID- 7562256
TI  - The abnormal isoform of the prion protein accumulates in late-endosome-like
      organelles in scrapie-infected mouse brain.
AB  - The prion encephalopathies are characterized by accumulation in the brain of the
      abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of
      formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie
      infected mouse brain was used to show, both biochemically and by double-labelled
      immunogold electron microscopy, that proteinase K-resistant PrPsc is enriched in
      subcellular structures which contain the cation-independent mannose 6-phosphate
      receptor, ubiquitin-protein conjugates, beta-glucuronidase, and cathepsin B,
      termed late endosome-like organelles. The glycosylinositol phospholipid membrane
      anchored PrPc will enter such compartment for normal degradation and the
      organelles may therefore act as chambers for the conversion of PrPc into
      infectious PrPsc in this murine model of scrapie.

PMID- 7562257
TI  - Distribution of cyclooxygenase isoforms in murine chronic granulomatous
      inflammation. Implications for future anti-inflammatory therapy.
AB  - Inhibition of the enzyme cyclooxygenase (COX) is the basis for the mechanism of
      action of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as a
      constitutive (COX-1) and a mitogen-inducible (COX-2) isoform. The relative
      contribution of COX-1 and COX-2 to inflammation is unknown. This study
      investigated COX activity and the distribution of COX-1 and COX-2 during the
      development of a murine air pouch model of chronic granulomatous inflammation.
      COX activity progressively rose and was maximal at day 14. Of the COX metabolites
      measured, PGE2 was the greatest > 6-keto PGF1a > TXB2 > PGF2a. By day 7, COX-2
      labelled fibroblast- and macrophage-like cells were observed and their number and
      distribution increased with time. At all time points, endothelial cells of
      venules in the loose connective tissue of the dermis showed immunoreactivity for
      COX-2. After day 14, labelling of capillaries in the granuloma was also observed.
      This study is the first to show that COX-2 is the predominant COX isoform in all
      stages of the inflammatory response. These results suggest that selective
      inhibition of COX-2 may prove more beneficial, with fewer gastric and renal side
      effects, than existing NSAID therapy for the treatment of chronic inflammatory
      diseases.

PMID- 7562259
TI  - Drug use by homicide offenders.
AB  - This article uses data derived from interviews with 268 homicide offenders
      incarcerated in New York State correctional facilities to examine their drug use
      prior to and at the time of the homicide, and their perceptions as to whether and
      how the homicides were related to their drug use. Most respondents who used a
      drug were not hard-core users of that drug. About one in five of the respondents
      could be considered polydrug abusers. Thirty percent of the sample believed that
      the homicide was related to their drug use. Alcohol was the drug most likely to
      be implicated in these homicides. The implications of this research are
      discussed.

PMID- 7562258
TI  - Artefacts in electron microscopy: ultrastructural features of chrysiasis.
AB  - Eleven cases of chrysiasis have been studied ultrastructurally and by electron
      probe microanalysis. Tissue samples were examined both with and without osmium
      and uranyl acetate staining. There was a significant morphological difference in
      the appearance of the gold deposits within aurosomes between the two groups. The
      untreated group showed finely granular deposits, often arranged in a linear
      fashion. Aurosomes from samples treated with osmium and uranyl acetate showed
      more electron-dense deposits and star-like formations. We propose that treatment
      of the tissue with osmium and uranyl acetate causes a change in the electron
      microscopic appearance of aurosomes, including the formation of the
      characteristic star-like aurosomes.

PMID- 7562261
TI  - The demedicalization of methadone maintenance.
AB  - The institution of methadone maintenance as a treatment modality for heroin
      addiction in the mid-1960s was part of the growing medicalization of social
      problems in the United States. The definition of deviance as "sickness" rather
      than "badness" set the stage for America's first harm-reduction strategy. By the
      1970s methadone maintenance was seen as a way to reduce drug-related crime, and
      federally funded programs proliferated. Accompanying methadone's phenomenal
      expansion was increased regulation, bureaucratization, and criticism. The early
      1980s brought the Reagan era, fiscal austerity, the new "just say no" abstinence
      morality, and demedicalization of methadone maintenance. By the time needle
      sharing was recognized as a major contributing factor in the spread of HIV,
      methadone had been transformed into a largely fee-for-service, short-term,
      begrudgingly tolerated treatment modality. Ironically, while other countries were
      able to use methadone to curb the spread of AIDS, the United States refused to
      facilitate its expansion, and in fact impeded it. To the frustration of
      proponents and consumers, this original harm-reduction tool, with the potential
      to impact the epidemic, was demedicalized and remains marginalized.

PMID- 7562260
TI  - Illegal drug use, alcohol and aggressive crime among Mexican-American and white
      male arrestees in San Antonio.
AB  - This research explores the relationship between use of certain drugs and
      aggressive crimes among Mexican-American and White male arrestees in San Antonio,
      Texas, for 1992. This is based on a Drug Use Forecasting (DUF) sample of 534 male
      arrestees administered a drug urine analysis test and questionnaire by the
      Department of Justice and the city of San Antonio. Using a four-way asymmetrical
      analysis, logit-models were tested to examine the relationships between the
      response variable, the types of crimes charged (nonaggressive versus aggressive)
      and a set of exploratory variables, ethnicity (White versus Hispanic), drug test
      results (positive versus negative), and alcohol use (infrequent versus frequent).
      The logit-analysis allows the specification of a subset of relevant models to be
      tested for their adequacy of fit. Findings indicate a complex but interpretable
      pattern between drug use, alcohol use patterns, and aggressive crimes. A
      surprising finding was that more aggressive crimes were committed by all men
      testing negative for drugs. Mexican-Americans with frequent alcohol use and
      testing positive for drugs were twice as likely to commit an aggressive crime (a
      crime associated with violence) than Whites in the same subgroup. The implication
      of these findings for prevention strategies aimed at alcohol and other drug users
      involved in violent behavior is discussed.

PMID- 7562262
TI  - Treatment intensity and reduction in drug use for cocaine-dependent methadone
      patients: a dose-response relationship.
AB  - This study examined the impact of treatment intensity on cocaine use. Seventy
      seven cocaine-using methadone patients were enrolled in a six-month, structured,
      manual-driven, cognitive-behavioral treatment program. Sessions consisted of five
      individual and/or group sessions per week. At intake subjects showed extensive
      polydrug abuse, psychiatric comorbidity, criminal histories, and HIV risk
      behaviors. Treatment intensity was measured by dividing number of sessions
      attended into quartiles. Paired comparisons, within treatment quartiles, were
      made between subjects' intake and six-month self-reports of cocaine use. Subjects
      in quartiles two through four showed significant reductions in frequency of
      cocaine use at follow-up, with subjects who received the most treatment showing
      the greatest reductions in cocaine use. Bivariate and multivariate analyses
      showed that treatment sessions attended remained a strong predictor of reduction
      in cocaine use at follow-up, even after controlling for drug use at intake and
      background variables. The results indicate that there is a substantial treatment
      dose-response relationship.

PMID- 7562265
TI  - Modified tobacco use as a risk-reduction strategy.

PMID- 7562264
TI  - Relapse prevention for individuals with developmental disabilities, borderline
      intellectual functioning, or illiteracy.
AB  - The use of relapse-prevention-specific interventions in clinical addictions
      treatment programs is widely supported. While there is considerable information
      and research available regarding relapse prevention, there is little if any
      available regarding such interventions for individuals with developmental
      disabilities, borderline intellectual functioning, or illiteracy. A group design
      is proposed for this population that can be easily utilized by programs
      struggling with a lack of resources for the target population. This group model
      can be applied to individuals who are dually diagnosed because it is versatile
      and nonthreatening.

PMID- 7562266
TI  - The changing relationship between therapeutic communities and 12-Step programs: a
      survey.

PMID- 7562263
TI  - The use of node-link mapping in drug abuse counseling: the role of attentional
      factors.
AB  - This study extends previous research on the use of node-link mapping during
      counseling by addressing the effect that this visual representation technique has
      on clients with attentional problems. Participants were 13 counselors in a
      methadone treatment program and their 93 opioid-addicted clients who had been in
      treatment for more than three months. Both counselors and clients were randomly
      assigned to mapping-enhanced or standard counseling. Based on a self-report
      measure assessing attention-related problems of clients, they were categorized as
      having either adequate or poor levels of attentional stamina and attentional
      control. Consistent with previous findings, clients in mapping-enhanced
      counseling had lower percentages of urine samples that were positive for cocaine
      or heroin. In addition, results suggest that mapping has greater benefits in
      terms of session attendance and program perception for clients with poor
      attentional stamina.

PMID- 7562267
TI  - Psychoactive properties of pergolide mesylate.

PMID- 7562268
TI  - Sympathetic response to betel chewing.

PMID- 7562269
TI  - Canavan disease: from spongy degeneration to molecular analysis.
AB  - Establishing the basic defect in Canavan disease has led to reliable biochemical
      methods for the diagnosis of this disease. The isolation of the gene and
      identification of mutations causing Canavan disease have led to the possibility
      of using DNA methods for the diagnosis of Canavan disease and for carrier
      detection. A surprising finding is the high carrier frequency of this gene defect
      among Ashkenazi Jewish people. Analysis for two mutations leads to the
      identification of 97% of Jewish patients with Canavan disease, and screening of
      Ashkenazi Jews is possible. N-Acetylaspartic acid has been considered to be an
      inert compound. The pathophysiology of Canavan disease links lack of NAA
      hydrolysis to a severe, debilitating white matter disease. Currently, NAA is
      being studied in many other brain disorders, such as Alzheimer disease,
      Huntington disease, and stroke. However, the only disease with a specific defect
      in the metabolism of NAA is Canavan disease. An animal model for Canavan disease
      is needed to study some of the questions regarding the role of NAA in brain
      tissue, and for the study of therapeutic modalities, including gene therapy.

PMID- 7562270
TI  - Efficacy, immunogenicity, safety, and use of live attenuated chickenpox vaccine.

PMID- 7562271
TI  - Penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae
      causing sepsis and meningitis in children with sickle cell disease.
AB  - OBJECTIVE: We investigated the possibility that antimicrobial-resistant
      pneumococci were causing invasive disease in children with sickle-cell disease
      (SCD). STUDY DESIGN: Records of all children with SCD observed at the Mid-South
      Sickle Cell Center (MSSCC) at LeBonheur Children's Medical Center were reviewed
      from January 1990 to June 1994. Children with SCD and pneumococcal sepsis were
      identified. The Streptococcus pneumoniae isolates from these children were
      examined for serotype and antimicrobial susceptibilities. Two additional children
      not observed in the MSSCC had pneumococcal sepsis caused by penicillin-resistant
      isolates and were also included. RESULTS: Antimicrobial susceptibility testing of
      the six penicillin-resistant isolates revealed that four were resistant to
      trimethoprim-sulfamethoxazole, two to erythromycin, and one to clindamycin. The
      two isolates that were resistant to ceftriaxone also were multiply resistant.
      From the MSSCC, 26 children had pneumococcal sepsis during the 4 1/2-year period
      studied. Five of these children (19%) died. Four (15%), including one who died,
      were infected with penicillin-resistant strains. CONCLUSION: Pneumococcal sepsis,
      meningitis, and infections of other foci in children with SCD may be caused by S.
      pneumoniae that is resistant to one or more antimicrobial agents, including
      penicillin. The addition of vancomycin to the antibiotics currently used for
      initial management should be considered in areas where the antibiotic resistance
      of S. pneumoniae is prevalent.

PMID- 7562272
TI  - Streptococcus pneumoniae colonization in the young child: association with otitis
      media and resistance to penicillin.
AB  - OBJECTIVE: To determine the nasopharyngeal colonization rate of penicillin
      susceptible and penicillin-resistant strains of Streptococcus pneumoniae in young
      children, and to assess its relationship with the incidence of otitis media.
      DESIGN: Observational study in 215 children younger than 6 years of age who
      received care in the Vanderbilt Vaccine Clinic from September 1, 1992, to August
      31, 1993. RESULTS: Of 842 nasopharyngeal cultures obtained, results for 44% of
      the cultures were positive for S. pneumoniae; 73% of the isolates were serotypes
      6, 14, 19, or 23. Younger children had significantly higher rates of pneumococcal
      colonization than older children, with a peak at 1 year of age. By microdilution
      susceptibility testing, 37% of the cultures with positive results were
      intermediately or highly resistant to penicillin. Significantly more serotype 19
      and 23 isolates were penicillin resistant than organisms of other serotypes.
      Children younger than 2 years of age had a twofold higher percentage of resistant
      isolates than those older than 2 years of age. A significant association was
      noted between nasopharyngeal carriage of S. pneumoniae and acute otitis media (p
      = 0.0002); however, the incidence of acute otitis media did not differ
      significantly between children colonized with penicillin-susceptible or
      penicillin-resistant strains. Unresolved otitis media was diagnosed more often in
      children who were colonized with resistant organisms than in children colonized
      with susceptible strains (p = 0.04). CONCLUSIONS: There was a high rate of
      nasopharyngeal carriage of penicillin-resistant S. pneumoniae in this population
      of young children. Nasopharyngeal colonization was associated with an increased
      incidence of acute otitis media, and penicillin resistance was associated with an
      increased incidence of unresolved otitis media.

PMID- 7562273
TI  - Shortened survival in infants vertically infected with human immunodeficiency
      virus with elevated p24 antigenemia.
AB  - OBJECTIVE: To determine whether the amount of p24 antigenemia in the first 6
      months of life is a predictor of survival in children infected vertically with
      human immunodeficiency virus type 1. METHODS: A retrospective study of vertically
      infected infants and children who were followed prospectively from early infancy
      and who had quantitation of plasma p24 antigen concentration in the first 6
      months of life. Infants were first stratified by duration of survival as infants
      who died before 2 years of age (short-term survivors) and infants who survived to
      2 years of age (intermediate-term survivors). The median p24 antigen
      concentration and the proportion of infants in each group with high
      concentrations of antigen were compared. Analyses with and excluding all p24
      determinations made after the use of antiretroviral agents were compared Kaplan
      Meier product limit analysis was used to compare survival in infants with low and
      high antigenemia during the first 6 months of life. RESULTS: The median p24
      antigen concentration in 15 short-term survivors was 228 pg/ml, compared with 14
      pg/ml in 26 intermediate-term survivors (p < 0.05). The proportion of children
      with > 100 pg/ml of p24 was higher in short-term than in intermediate-term
      survivors (p = 0.01). Survival to 2 years of age in infants in whom all p24
      antigen values during the first 6 months of life were 100 pg/ml or less was 91%,
      in comparison with 39% in infants with values greater than 100 pg/ml (p =
      0.0017). CONCLUSIONS: Elevated p24 antigenemia in the first 6 months of life is
      associated with shorter survival and may be a useful predictor of outcome.

PMID- 7562274
TI  - Influence of host genotype on progression to acquired immunodeficiency syndrome
      among children infected with human immunodeficiency virus type 1.
AB  - OBJECTIVE: To study the role of host genotype in pediatric infection with human
      immunodeficiency virus type 1 (HIV-1) and progression to acquired
      immunodeficiency syndrome (AIDS). METHODS: Human leukocyte antigen (HLA) class II
      and complement C4 genotypes were determined by means of molecular genetic
      techniques for 243 black children born to HIV-1-infected mothers in New York City
      and San Francisco. Survival, cumulative incidences of opportunistic infections
      and encephalopathy, and rates of CD4+ T cell decline were compared in children of
      different genotypes. RESULTS: Among HIV-1-infected children, the HLA-DR3
      haplotype (DRB1*0301-DQA1*0501-DQB1*0201) was associated with increased incidence
      of encephalopathy, faster rate of CD4+ cell decline, and death before 2 years of
      age. Deletion of the C4A gene was independently associated with increased
      incidences of encephalopathy and early death. DPB1*0101 was associated with
      survival to at least 2 years of age. The presence of DQB1*0604 was associated
      with increased risk of HIV infection. CONCLUSIONS: These results are consistent
      with previously reported associations between HLA genotypes and faster
      progression to AIDS among HIV-infected adults. The DR3 haplotype and C4A deletion
      may reflect the same underlying mechanism of susceptibility in that the DR3
      haplotype is in linkage disequilibrium with other C4A null alleles. In addition,
      the class II locus DPB1 may have an independent effect on survival.

PMID- 7562275
TI  - Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in
      infants with cow milk allergy.
AB  - OBJECTIVE: To determine the antigenicity, nutritional adequacy, and growth
      promoting efficacy of protein hydrolysate or amino acid-derived formulas in
      infants with cow milk allergy. STUDY DESIGN: Several protein hydrolysate or amino
      acid-derived formulas were graded for beta-lactoglobulin content and skin
      reactivity in 74 atopic children with cow milk allergy proved by a double-blind,
      placebo-controlled challenge. A randomized, prospective follow-up study of 9
      months included 22 infants with a mean age of 6 months (95% confidence interval,
      4 to 7), who were fed an extensively hydrolyzed whey formula (group We), and 23
      infants with a mean age of 17 (95% confidence interval, 4 to 7) months, who were
      given an amino acid-derived formula (group AA). RESULTS: Both formulas were
      clinically and biochemically tolerated. The mean concentration of essential amino
      acids in plasma was lower in group We but higher in group AA compared with values
      for breast-fed control infants (p = 0.001). There was a different trend between
      the groups in weight (p = 0.09) and length (p = 0.006). Growth was promoted in
      group AA during the follow-up; it was constant during the first months, followed
      by a gradual decline in rate in group We. In both groups, atopic eczema improved
      significantly and progressively, and a downward trend was found in serum total
      and milk-specific IgE concentrations, proving the efficacy of both formulas.
      CONCLUSIONS: Extensively hydrolyzed formulas are safe and effective for most
      infants; an amino acid-derived formula may be preferable for infants with
      multiple food allergies, especially for the maintenance of normal growth.

PMID- 7562276
TI  - Eosinophil cationic protein in serum and nasal washes from wheezing infants and
      children.
AB  - OBJECTIVE: To compare eosinophil counts and concentrations of eosinophil cationic
      protein (ECP) in serum and nasal wash fluid from wheezing infants and children
      with those from age-matched children without respiratory tract symptoms. DESIGN:
      A case-control study of 71 children treated for wheezing and 59 control subjects
      in the University of Virginia Pediatric Emergency Department. The patients ranged
      from 2 months to 16 years of age. Eosinophil numbers and ECP concentrations were
      assessed in serum and nasal washes. Total serum IgE was measured and the
      radioallergosorbent test was used to measure IgE antibody to common inhalant
      allergens. RESULTS: Among children less than the age of 2 years, markedly
      elevated levels of ECP (> 200 ng/ml) were measured in nasal washes from 9 (41%)
      of 22 wheezing patients and 1 (6%) of 17 control subjects (p < 0.03). None of
      these children had a positive radioallergosorbent test result for IgE antibody to
      common aeroallergens or a nasal smear containing 10% eosinophils. Few of the
      wheezing children under 2 years of age had either increased concentrations of
      total IgE or ECP in their serum or an elevated total blood eosinophil count.
      After the age of 2 years, the percentage of patients with nasal ECP levels
      greater than 200 ng/ml was also significantly higher in wheezing children than in
      control subjects (p < 0.001), and a positive correlation was observed between ECP
      concentrations in their nasal washes and other eosinophil responses (total blood
      eosinophil counts, serum ECP levels, and nasal eosinophil counts). CONCLUSION:
      Increased concentrations of ECP were detected in nasal washes from wheezing
      infants and children, indicating that eosinophils may contribute to the
      pathogenesis of airway inflammation in some children who wheeze early in life.

PMID- 7562277
TI  - Cystic fibrosis-associated colitis and fibrosing colonopathy.
AB  - OBJECTIVE: To describe our experience with cystic fibrosis (CF)-associated
      colitis and fibrosing colonopathy, and to assess treatment strategies. STUDY
      DESIGN: We reviewed hospital charts and autopsy reports of all University of
      Minnesota patients with CF between 1975 and August 1994. We identified six
      patients with colonopathy and compared them with a cohort of 79 patients with CF
      in the same age range and seen during the same period. RESULTS: All patients with
      colonopathy had bloody diarrhea; five of the six had abdominal pain. Stool
      frequency and related symptoms distinguished the patients with colonopathy from
      the cohort population. All took a higher median dose of pancreatic enzymes than
      the cohort population during the 3 months preceding the onset of symptoms (p <
      0.002). For all six patients, barium studies revealed loss of haustration, and
      shortening and diffuse narrowing of the colonic lumen with relative rectal
      sparing. The distal ileal mucosa was irregular in four patients. A
      histopathologic study reveal fibrosis of the submucosa or lamina propria, and
      focal acute cryptitis in all six patients. Other features included ascites (2/6)
      and nodular regenerative hyperplasia of the liver (1/6). One patient continues to
      have symptoms, three had subtotal colectomy, and the condition of two improved
      after a regimen including a low-fat diet, withholding of pancreatic enzymes, and
      supplemental parenteral nutrition was initiated. CONCLUSIONS: Fibrosing
      colonopathy represents a newly recognized gastrointestinal complication of cystic
      fibrosis. Affected persons have taken larger doses of pancreatic enzymes than
      similar patients with cystic fibrosis, and have bloody diarrhea. We developed a
      medical protocol that may avoid surgical resection of the colon in some of these
      patients.

PMID- 7562278
TI  - Measured and predicted resting metabolic rate in obese and nonobese adolescents.
AB  - OBJECTIVES: The validity of equations for the calculation of resting metabolic
      rate (RMR) were studied and new predictive equations were developed. STUDY
      DESIGN: The RMR was measured in a sample of 371 10- to 16-year-old prepubertal
      and postpubertal children. The study group included 193 male (116 nonobese and 77
      obese) and 178 female (119 nonobese and 59 obese) subjects; for each group the
      RMRs predicted from five equations recommended for this age group were compared.
      The RMR was assessed by indirect calorimetry with a ventilated hood system for 45
      minutes after an overnight fast. Body composition was estimated from skin-fold
      measurements. RESULTS: The mean +/- SD RMR was found to be 5600 +/- 972 kJ/24 hr
      and 7223 +/- 1220 kJ/24 hr in nonobese and obese boys, and 5112 +/- 632 kJ/24 hr
      and 6665 +/- 1106 kJ/24 hr in nonobese and obese girls, respectively. All five
      equations applicable to 10- to 16-year-old children overestimated RMR by 7.5% to
      18.1% (p < 0.001 for each equation). Stepwise regression analysis, with
      independent variables such as age, weight, height, and gender, allowed
      development of new predictive equations for the calculation of RMR in 10- to 16
      year-old boys (RMR = 50.9 Weight (kg) + 25.3 Height (cm) -50.3 Age (yr) + 26.9;
      R2 = 0.884, p < 0.0001) and girls (RMR = 51.2 Weight (kg) + 24.5 Height (cm) -
      207.5 Age (yr) + 1629.8; R2 = 0.824, p < 0.0001). These predictive equations were
      tested in a second, independent cohort of children (80 male and 61 female
      subject) and were found to give a reliable estimate of RMR in 10- to 16-year-old
      obese and nonobese adolescents. CONCLUSIONS: The currently used predictive
      equations overestimate RMR in 10- to 16-year-old children. The use of the newly
      developed equations is recommended.

PMID- 7562279
TI  - Daily physical activity of schoolchildren with spastic diplegia and of healthy
      control subjects.
AB  - OBJECTIVE: To assess the differences in daily physical activity between children
      with spastic diplegia and healthy schoolchildren, to determine whether special
      physical activity programs are needed in the population with cerebral palsy.
      DESIGN: Cross-sectional design. SETTING: Children's rehabilitation center
      Franciscusoord (day care center) and elementary schools. SUBJECTS: Children with
      spastic diplegia (5 boys; mean (+/- SD) age 8.0 +/- 1.4 years; 9 ambulant, 1
      wheelchair use) and healthy children (5 boys; mean (+/- SD) age 8.4 +/- 1.0
      years). MEASUREMENTS: Total daily energy expenditure (TEE) and sleeping metabolic
      rate (SMR) were measured by the doubly labeled water technique and a respiration
      chamber. The TEE/SMR ratio was used as an index for the level of daily physical
      activity. RESULTS: The TEE/SMR ratio under normal daily conditions in the
      children with cerebral palsy (mean +/- SD): 1.56 +/- 0.19) was significantly
      lower (p < 0.05) than in their healthy peers (mean +/- SD: 1.83 +/- 0.23) and was
      similar to the TEE/SMR ratio in a room-sized chamber. CONCLUSION: Children with
      spastic diplegia are considerably less active than their healthy peers. We
      recommend special physical activity programs for these children.

PMID- 7562280
TI  - Exercise-induced anaphylaxis related to specific foods.
AB  - We describe the case, documented by challenge results, of a 16-year-old girl with
      exercise-induced anaphylaxis associated with eating pizza and a cheese sandwich.
      Patients in whom a specific coprecipitating food has been identified should avoid
      it for at least 12 hours before exercise. All patients should be instructed to
      avoid eating 6 to 8 hours before exercise, discontinue exercise at the first sign
      of symptoms, and exercise only with a companion prepared to administer
      epinephrine.

PMID- 7562281
TI  - Anti-pneumococcal antibody levels three to seven years after first booster
      immunization in children with sickle cell disease, and after a second booster.
AB  - We measured pneumococcal antibody levels in 55 patients (ages 7 to 20 years) with
      sickle cell disease 3 to 7 years after the first booster immunization. Only 6 of
      the children had protective levels of antibodies (> 300 ng/ml) against all 12
      serotypes tested. Thirty-two children (58%) had suboptimal levels against 1 to 3
      serotypes; 17 had suboptimal levels against 4 to 10 serotypes. Ten patients from
      the latter group (ages 13 to 17 years) received a second booster 6 to 8 years
      after the first booster immunization, and had a marked increase in antibody
      levels against all serotypes with the exception of serotypes 3 and 4 in two
      patients and serotype 6A in one patient.

PMID- 7562282
TI  - Age-related changes in colon motility.
AB  - To assess age-related changes, we analyzed 32 colon manometry studies of children
      referred for motility studies and found not to have colonic disease. Colon
      motility was recorded by endoscopically placed water-perfused catheters. There
      was an inverse correlation between the number of high-amplitude propagated
      contractions and age, before and after administration of a meal; colonic
      contractions different from the high-amplitude propagated contractions increased
      with age.

PMID- 7562283
TI  - Peroxisomal assembly defects: clinical, pathologic, and biochemical findings in
      two patients in a newly identified complementation group.
AB  - We describe the clinical, pathologic, and biochemical findings for two peroxisome
      deficient patients in a newly identified complementation group. Both patients had
      biochemical findings typical of patients with peroxisome biogenesis disorders.
      However, whereas one patient had the typical clinicopathologic features of
      Zellweger syndrome, the other patient's phenotype was atypical.

PMID- 7562284
TI  - Heterozygosity for long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
      and deterioration in liver function in a newborn infant infected with human
      immunodeficiency virus.
AB  - A child with perinatally acquired human immunodeficiency virus infection had
      rapidly progressive hepatic dysfunction, as had her older sibling who died.
      Urinary organic acid studies revealed 3-hydroxydicarboxylic aciduria, and
      cultured skin fibroblasts had reduced activity of 3-hydroxy-coenzyme A
      dehydrogenase. The introduction of a low fat diet resulted in marked improvement
      in clinical status and reversal of the liver disease. This case illustrates the
      necessity of metabolic evaluation in patients with liver dysfunction, even when
      other causes of liver dysfunction are present.

PMID- 7562285
TI  - Phosphorylase b kinase deficiency glycogenosis with cirrhosis of the liver.
AB  - We describe an Arab girl with complete absence of phosphorylase b kinase activity
      in the liver, symptomatic hypoglycemia, and persistently elevated serum
      aminotransferase values whose symptoms did not lessen with age; sequential liver
      biopsies showed progression to cirrhosis. Cirrhosis could not be ascribed to any
      other known cause. We conclude that type IX glycogenosis is not always associated
      with a benign outcome.

PMID- 7562286
TI  - Myelodysplasia and deficiency of uridine diphosphate-galactose 4-epimerase.
AB  - A 4-year-old girl known to have peripheral uridine diphosphate-galactose 4
      epimerase deficiency was examined for bruising and thrombocytopenia. She had
      dysplastic peripheral blood and bone marrow changes, with a global platelet
      function defect. Uridine diphosphate-galactose-4-epimerase participates in a
      metabolic pathway that provides substrates for posttranslational glycosylation of
      secreted and membrane glycoproteins, including hematopoietic growth factors and
      their receptors; there may be a causal relationship between the two disorders.

PMID- 7562287
TI  - Vulnerability of respiratory control in healthy preterm infants placed supine.
AB  - OBJECTIVE: We tested the hypothesis that healthy preterm infants have attenuated
      ventilatory responses to hypercapnia, associated with a decreased rib cage
      contribution to ventilation, in the supine versus prone position. STUDY DESIGN:
      We elicited hypercapnic ventilatory responses from 19 healthy preterm infants
      (postconceptional age 35 +/- 1 weeks) who were being prepared for hospital
      discharge. The O2 saturation was continuously monitored. Before and during CO2
      rebreathing, ventilation was measured with a nasal mask pneumotachygraph and was
      derived from chest wall motion as determined by respiratory inductance
      plethysmograph. This measuring method allowed us to compare both ventilation and
      the percentage rib cage contribution to ventilation between supine and prone
      positions. Statistical analysis employed analysis of variance with repeated
      measures. RESULTS: The supine position was associated with a higher respiratory
      rate (p < 0.02) and lower O2 saturation (p < 0.007) than the prone position. The
      increase in ventilation in response to hypercapnia was lower in the supine than
      in the prone position. This was statistically significant for the respiratory
      inductance plethysmograph (p < 0.008) but not the pneumotachygraph (p = 0.077),
      and was associated with a smaller rib cage contribution to ventilation in the
      supine than in the prone position (p < 0.0001). CONCLUSION: Respiratory control
      may be vulnerable when healthy preterm infants are placed supine. Widespread
      avoidance of the prone position may not be appropriate for such patients.

PMID- 7562288
TI  - Randomized, controlled trial of amoxicillin prophylaxis for prevention of
      catheter-related infections in newborn infants with central venous silicone
      elastomer catheters.
AB  - OBJECTIVE: To clarify the effectiveness of amoxicillin prophylaxis in the
      prevention of catheter-related infections. METHOD: We performed a randomized,
      controlled, sequential, prospective trial in newborn infants undergoing
      percutaneous central venous catheterization. RESULTS: Seventy-five infants
      (median birth weight, 1240 gm; median age at catheter insertion, 3 days) received
      prophylactic amoxicillin (100 mg/kg per day); 73 infants in the control group
      (median birth weight, 1170 gm; median age, 2 days) received no routine
      prophylactic antibiotic treatment. No infant receiving amoxicillin had
      septicemia, whereas two infants (2.7%) in the control group did; suspected
      septicemia (positive clinical and laboratory findings but negative blood culture
      results) was found in 3 infants in the amoxicillin group and in 6 of the control
      group (not significantly). Bacterial contamination of the catheter tip at removal
      was significantly reduced in the amoxicillin group (13.3% vs 28.8% in control
      subjects; p < 0.05). Negligible differences were found in duration of
      catheterization (median, 15 days in both groups), or the number of thrombotic
      (9.3% vs 2.7% in control subjects) and other catheter-related complications
      between the groups. CONCLUSION: A low incidence of catheter-related infections
      can be achieved in neonates with central venous catheters without using
      prophylaxis with an antibiotic.

PMID- 7562289
TI  - Effect of physical activity on bone mineralization in premature infants.
AB  - OBJECTIVE: A 4-week pilot study was done with 26 preterm infants to evaluate
      whether a physical activity program would result in greater bone mineralization.
      DESIGN: Subjects were matched by birth weight, gender, and gestational age, and
      randomly assigned to the physical activity program (group EX; n = 13) or to the
      control group (group C; n = 13). Physical activity consisted of range of motion
      with passive resistance to all extremities for 5 to 10 minutes daily. Baseline
      and 4-week values were determined for both bone mineral analyses and serum levels
      of calcium, phosphate, alkaline phosphatase, parathyroid hormone, and 25-hydroxy
      vitamin D. RESULTS: Despite similar nutrient intake at advised levels for preterm
      infants, EX infants gained more weight than control subjects (17.8 vs 13.4 gm/kg
      body weight per day; p = 0.01). A difference in radial bone mass and density
      change as determined by single-beam photon absorptiometry (+/- 2% error) was
      found between groups (p = 0.006 by analysis of covariance). Changes in bone width
      and in bone mineral content and density were enhanced by physical activity. Group
      EX infants had 12%, 18%, and 34% gains in bone width and in bone mineral density
      and content, respectively; group C infants had only a 2% gain in bone width and
      11% and 14% losses from baseline in bone mineral content and density,
      respectively, during the 4-week study. Serum biochemical values were similar in
      the groups except for lower alkaline phosphatase levels in group EX. There was a
      negative association between bone mineral content and parathyroid hormone values:
      r = -0.83, p = 0.01. CONCLUSIONS: A physical activity program may increase the
      effects of adequate nutrition in healthy preterm very low birth weight infants by
      promoting weight gain and bone mass and by decreasing the risk of osteopenia.

PMID- 7562290
TI  - Absorption of lactose, glucose polymers, or combination in premature infants.
AB  - STUDY OBJECTIVE: To determine the digestion and absorption of lactose, a
      combination of lactose and glucose polymers, and glucose polymers alone in
      infants born at 28 to 42 weeks of gestation. DESIGN: Each infant received the
      three carbohydrate solutions (85 gm/L concentration) in random order. SETTING:
      Tertiary care urban children's hospital. INTERVENTIONS: A double-lumen perfusion
      catheter was placed in the duodenum-jejunum. Absorption was defined as the
      disappearance of the carbohydrate and all its components (e.g., for lactose:
      galactose, glucose). MEASUREMENTS AND MAIN RESULTS: Absorption of lactose was
      less than that of the lactose-glucose polymer combination and the glucose
      polymers alone. There was no relationship between lactose absorption and
      postnatal age, whereas absorption of the lactose-glucose polymer combination and
      the glucose polymers alone correlated with age. Lactose absorption was not
      related to the number of days that the infants received full-strength feedings or
      the total number of days of feeding before the study, whereas absorption of both
      the lactose-glucose polymer combination and the glucose polymers alone was
      related to both. Absorption of the three solutions was not related to gestational
      age or to the number of days before the initial feeding. Lactose absorption was
      greater in infants who received formula alone than in infants fed formula
      together with human milk. CONCLUSIONS: Premature infants do not digest and absorb
      lactose as well as glucose polymers. However, lactose does not impair the
      absorption of glucose polymers. Lactose assimilation is not affected by
      maturation, but the type of diet may affect lactose digestion and absorption. In
      contrast, digestion and absorption of glucose polymers are related to both
      postnatal age and diet.

PMID- 7562291
TI  - Severe retinopathy of prematurity in infants with birth weights less than 1250
      grams: incidence and outcome of treatment with pharmacologic serum levels of
      vitamin E in addition to cryotherapy from 1985 to 1991.
AB  - OBJECTIVE: To determine the effect of vitamin E prophylaxis and treatment on the
      sequelae of severe (threshold) retinopathy of prematurity (ROP) in infants
      treated with cryotherapy at Pennsylvania Hospital from 1985 to 1991. STUDY
      DESIGN: Beginning on day 0, all infants with birth weights < or = 1250 gm
      received supplements of vitamin E using standard preparations. Serum E levels of
      23 to 58 mumol/L (1 to 2.5 mg/dl) were targeted for infants with immature retinal
      vasculature or ROP of stage 2 or less in severity, and levels of 58 to 81 mumol/L
      (2.5 to 3.5 mg/dl) for infants with prethreshold ROP. At diagnosis of threshold
      ROP, treatment with a parenteral investigational new drug preparation of alpha
      tocopherol was begun to raise serum levels to the pharmacologic range (93 to 116
      mumol/L or 4 to 5 mg/dl). Within 3 days of diagnosis, and at the discretion of
      the retinal specialist, one or both eyes were treated with cryotherapy. Visual
      outcome at 4 years was compared with the 42-month outcome reported for eyes in
      the infants randomly assigned to treatment in the 1986-1987 Multicenter Trial of
      Cryotherapy for ROP (CRYO-ROP). RESULTS: Threshold ROP developed in 22 of 450
      surviving infants (age 3 months). All were treated with pharmacologic serum
      levels of vitamin E; 17 infants were also treated with cryotherapy (10 in one eye
      and 7 in both eyes). These 17 infants, in comparison with infants in the CRYO-ROP
      trial (n = 187), were at least at equal risk for poor visual outcome on the basis
      of birth weight, gestational age, the percentage of zone 1 ROP, and mean interval
      from appearance of ROP to diagnosis of prethreshold ROP, which was shorter at
      Pennsylvania Hospital (4.1 days for the Pennsylvania Hospital group, 10.3 days
      for the CRYO-ROP group). However, on the basis of the mean number of days from
      diagnosis of prethreshold to threshold ROP (12.5 days for Pennsylvania Hospital,
      10.5 days for CRYO-ROP) and the extent of extraretinal neovascularization at
      threshold (mean 7.9 sectors for Pennsylvania Hospital, 9.7 for CRYO-ROP),
      progression of retinopathy beyond the prethreshold stage had slowed and visual
      outcome in the eyes of infants at Pennsylvania Hospital treated with both
      cryotherapy and vitamin E (worse eye used for those treated with bilateral
      cryotherapy) was better than that reported for the treated eye of infants in the
      CRYO-ROP group (percentage of favorable visual acuity, 76% vs 48%, p = 0.04;
      percentage of normal structure posterior retinal pole, 71% vs 38%, p < or =
      0.02). CONCLUSIONS: In this small case series, the combination of cryotherapy
      with anti-oxidant prophylaxis and treatment appeared to decrease the severity and
      sequelae of threshold ROP. This hypothesis deserves testing in a large,
      randomized clinical trial.

PMID- 7562292
TI  - Association of Ureaplasma urealyticum colonization with chronic lung disease of
      prematurity: results of a metaanalysis.
AB  - OBJECTIVES: We performed a metaanalysis to determine whether there is an
      association between Ureaplasma urealyticum and chronic lung disease of
      prematurity (CLD); most studies involved small sample sizes, and the reported
      lack of statistical significance could have been due to inadequate power.
      METHODS: Articles were identified from the literature through a search of
      MEDLINE, Excerpta Medica, and Reference Update, with the search terms "Ureaplasma
      urealyticum," "CLD," and "bronchopulmonary dysplasia." The search was initially
      conducted in June 1994 and updated in March 1995. Abstracts were identified
      through a hand search of proceedings from two meetings for the years 1987 through
      1994. Summary data on frequency of CLD in U. urealyticum-colonized and
      uncolonized babies were independently determined by the three authors. Preterm
      and term neonates were included. Colonization required recovery of U. urealyticum
      from a respiratory or surface specimen. The presence of CLD at 28 or 30 days was
      determined. RESULTS: Seventeen publications comprising 13 full publications and 4
      abstracts were included in the analysis. The estimates for relative risk (RR)
      exceeded one in all studies, although the lower confidence interval included one
      in seven studies. The RR for the development of CLD in colonized neonates was
      1.72 (95% confidence interval, 1.5 to 1.96) times that for uncolonized neonates.
      The RR was not significantly different for abstracts versus full publications;
      studies focusing on extremely premature, low birth weight neonates versus studies
      including all neonates; and studies in which only endotracheal aspirates were
      used to define colonization versus others. The RR since surfactant use was
      somewhat lower than in studies in which receipt of surfactant was unknown.
      CONCLUSIONS: This metaanalysis supports a significant association between U.
      urealyticum colonization and subsequent development of CLD. A randomized,
      controlled trial showing a reduction in CLD through the use of an antibiotic
      effective against U. urealyticum would provide further support of a causative
      role for this agent.

PMID- 7562293
TI  - Activated protein C resistance in a neonate with venous thrombosis.
AB  - A term infant had a life-threatening inferior venal caval thrombosis during the
      first 24 hours of life. The plasma from the infant and his mother was found to be
      resistant to activated protein C and to be heterozygous for the factor V mutation
      (FV Leiden) associated with this disorder. The presence of this hereditary
      disorder should be considered in infants with thrombosis and in infants with
      conditions predisposing them to thrombosis.

PMID- 7562294
TI  - Severe intracranial hemorrhage in a newborn infant with transplacental transfer
      of an acquired factor VII:C inhibitor.
AB  - We describe a woman in whom inhibitors to factor VIII:C developed in her first
      pregnancy. The neonate had a factor VIII:C level of 1% and an inhibitor titer of
      5.2 Bethesda units. After an uneventful vaginal delivery, the boy had an
      intracranial hemorrhage at 5 days of age. To our knowledge, this is the first
      report of a bleeding complication in a newborn infant with transplacental
      transfer of an acquired factor VIII:C inhibitor.

PMID- 7562295
TI  - Hypertrophy of the tongue associated with inhaled corticosteroid therapy in
      premature infants.
AB  - We describe three infants in whom hypertrophy of the tongue developed while they
      were receiving beclomethasone inhalation therapy. The condition resolved after
      cessation of treatment, an outcome suggesting that tongue hypertrophy is a
      possible side effect of this therapy.

PMID- 7562296
TI  - High-dose intravenous methylprednisolone therapy for patients with Diamond
      Blackfan anemia refractory to conventional doses of prednisone.
AB  - OBJECTIVES: To assess the efficacy and toxicity of very high doses of
      glucocorticoids in patients with congenital pure red cell aplasia (Diamond
      Blackfan anemia) who did not respond to standard doses of prednisone. STUDY
      DESIGNS: We prospectively treated eight patients with transfusion-dependent
      Diamond-Blackfan anemia with high intravenous doses of methylprednisolone. All
      patients had previously not responded to one or more oral courses of prednisone
      in standard doses and were dependent on erythrocyte transfusions. Every patient
      initially received methylprednisolone at a dose of 30 mg/kg per day, followed by
      slow tapering for 4 weeks, but none responded. All patients then received a
      second treatment course starting at 100 mg of methylprednisolone per kilogram per
      day, again followed by slow tapering of the dosage. RESULTS: Three patients had a
      complete response that has been sustained for 21+, 31+, and 41+ months,
      respectively. One patient had a partial response. Toxic effects included a rise
      in serum alanine aminotransferase activity in all patients, transient diabetes
      mellitus in one child, and three episodes of bacteremia in two patients with
      intravenous access devices. CONCLUSIONS: We conclude that very high doses of
      methylprednisolone may induce sustained remission in some patients with
      transfusion-dependent Diamond-Blackfan anemia refractory to standard-dose
      prednisone therapy.

PMID- 7562297
TI  - Response to interferon therapy in children with chronic hepatitis C.
AB  - We evaluated the effect of interferon therapy and investigated factors that may
      influence the outcome in 18 children with chronic hepatitis C. A complete
      response was obtained in 10 children (56%). The titer for pretreatment serum
      virus ribonucleic acid (< or = 10(7) copies/ml) was correlated significantly with
      a complete response to therapy.

PMID- 7562298
TI  - Treatment of resistant oral aphthous ulcers in children with acquired
      immunodeficiency syndrome.
AB  - Four children with acquired immunodeficiency syndrome and aphthous oral ulcers
      with severe odynophagia were treated with a short oral course of prednisone. The
      lesions resolved completely with no adverse effects. We recommend considering a
      short course of prednisone for relief of symptoms in these patients.

PMID- 7562299
TI  - Effect of breast-feeding on hospitalization rates for lower respiratory
      infections.

PMID- 7562300
TI  - Predictors of cost-related outcomes of neonatal intensive care.

PMID- 7562301
TI  - Pancreatitis associated with hepatitis A viral infection.

PMID- 7562302
TI  - Benzathine as a cause for a false-positive test result for amphetamines.

PMID- 7562303
TI  - Mother-to-infant transmission of hepatitis C virus and breast-feeding.

PMID- 7562304
TI  - Risk of infection in children with hemoglobin S-beta-thalassemia.

PMID- 7562305
TI  - Efficacy and cost analysis of treating low birth weight infants with
      erythropoietin.

PMID- 7562306
TI  - Children first: is it ever going to happen??

PMID- 7562308
TI  - HIV/AIDS in the classroom: ethical and legal issues surrounding the public
      education of the HIV-infected child.
AB  - The AIDS crisis has paralyzed the minds of many rational individuals. This
      paralysis of the mind unfortunately is the result of fear and ignorance. The past
      10 years of the AIDS crisis has resulted in massive quantities of published
      reports regarding the biology, pathogenesis, transmission, clinical
      manifestations, and treatment of the AIDS virus. Yet there are those who still
      respond hysterically to the AIDS crisis. One group on which the results of much
      fear and ignorance have fallen is the school-aged child who is HIV infected. This
      article explores the issues of risk (to other school children and the HIV
      infected child), the legal rights of the HIV-infected child to a public
      education, and the role of the pediatric nurse practitioner in the disclosure of
      the HIV-infected child's diagnosis.

PMID- 7562307
TI  - Defining anemia in a preadolescent African American population.
AB  - Preadolescents often have poor nutritional habits. Demands for rapid growth
      require essential nutrients, vitamins, and minerals. The purpose of this study
      was to determine the prevalence/incidence of anemia in this age group and to
      identify possible predictors of anemia in African American preadolescents. A
      retrospective chart review of 455 African American preadolescents enrolled in two
      school-based clinics was conducted. Thirty percent of the sample had hematocrit
      values below 37% for males and below 35% for females. These data showed that
      anemia is an understated problem among African American preadolescents. No
      identifiable predictors were found; therefore routine screening for anemia is an
      essential component of the preadolescent annual health examination.

PMID- 7562310
TI  - The new food label: implications for primary care.
AB  - Providers of primary care need to integrate accurate nutritional advice into
      their practice. Understanding and explaining food labels should be one aspect of
      the role of the primary care provider. By becoming knowledgeable of the new food
      label mandated by the nutrition labeling regulations set forth by the Food and
      Drug Administration and the daily recommended values of nutrients, primary care
      providers will be able to help their clients to be better consumers and avoid
      misconceptions when making food choices.

PMID- 7562309
TI  - Care of the infant with gastroesophageal reflux and respiratory disease: after
      the Nissen fundoplication.
AB  - In cases of severe gastroesophageal reflux with failed medical management over a
      period of 3 to 6 months and/or extreme aggravation of respiratory disease,
      surgical intervention is necessary. The operative choice in infants and the most
      commonly used and successful surgery for the control of gastroesophageal reflux
      is the Nissen fundoplication. Care of the infant with a Nissen fundoplication
      should be focused on meeting the needs of the infant and the family. An
      understanding of the disease process, effects of fundoplication, and family
      process are essential for the nurse practitioner in planning care for these
      infants and their families.

PMID- 7562311
TI  - Thromboembolic complications in children and adolescents: who is at risk?

PMID- 7562312
TI  - Lymphomas in children.

PMID- 7562313
TI  - Vulvovaginitis in the prepubertal child.

PMID- 7562314
TI  - Newborn with port wine stain.

PMID- 7562315
TI  - Renewal of the Ryan White CARE Act.

PMID- 7562316
TI  - Violence prevention.

PMID- 7562317
TI  - President's message: priorities for children's health care: how to achieve
      healthy people 2000 goals.

PMID- 7562318
TI  - Effect of venous stasis and hypoproteinemia in gingival fluid formation in rats.
AB  - Experiments were performed to provide information on the mechanisms of the
      formation of gingival fluid in rats and on the determinants of its flow and
      composition. For this purpose we studied the effect of increasing net capillary
      filtration by venous stasis induced by multiple ligations of the jugular vein or
      by hypoproteinemia induced through puromycine nephrosis. A 1 microliter glass
      capillary was placed in the sulcus of the first maxillary molar for collection of
      gingival fluid (GF). Colloid osmotic pressure (COP) was determined in GF, in wick
      fluid from attached gingiva and buccal mucosa, and in plasma. Interstitial fluid
      hydrostatic pressure (Pi) was measured by micropuncture technique and the
      fractional removal rate of radio-labelled human serum albumin (kAlb) was recorded
      in attached gingiva and buccal mucosa. During venous stasis the gingival fluid
      flow increased from 1.7 microliters/h to 3.8 microliters/h, whereas COPGF fell
      from 14.1 mmHg to 8.8 mmHg. COP in wick fluid from gingiva was reduced from 10.3
      to 4.3 mmHg. Pi increased from 6.8 to 13.1 mmHg, and kAlb in sham-operated
      controls increased from 0.068 to 0.189 h-1. In buccal mucosa COPi was
      significantly decreased to 7.1 mmHg in rats with venous stasis, whereas Pi and
      kAlb remained unchanged compared to the sham-operated controls. In
      hypoproteinemic rats COPGF was 5.0 mmHg and COPp was reduced from 18.9 to 8.0
      mmHg. COPi declined from 8.9 mmHg to 2.4 mmHg in gingiva and from 8.1 mmHg to 2.7
      mmHg in buccal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562319
TI  - Histological study of lectin binding in regenerated rat junctional epithelium.
AB  - We investigated the expression of carbohydrate residues in regenerated junctional
      epithelium (JE) cells histopathologically with lectin staining to clarify the
      mechanisms responsible for the changes in their expression in JE cells derived
      from residual oral epithelium. Curettage and root planing procedures were
      performed on the buccal gingival sulci of rat first lower molars, and JE and
      connective tissues were completely removed. The mandibles were resected after 12
      h and 1, 2, 3, 4, 5, 7, 10 and 14 days, fixed with paraformaldehyde, decalcified
      with EDTA and embedded in paraffin. Serial sections were stained histochemically
      with four kinds of lectins (PNA, DBA, GS I, UEA I) to clarify the expression
      patterns of carbohydrate residues in regenerating epithelium. No binding of PNA
      or DBA was observed even when the regenerating epithelium was attached to the
      root surface, and they showed the same negative reactions as the basal cells of
      oral gingival epithelium (OGE). Positive reactions were, however, observed on the
      more stratified regenerating epithelium along the root surface. Positive
      reactions with GS I and negative reactions with UEA I were observed throughout
      the regeneration process, and these were the same as those observed in the basal
      cells of OGE. Therefore, we concluded that the basal cells and regenerated
      epithelium derived from OGE expressed the same carbohydrate residues.
      Furthermore, the expression of carbohydrate residues, one of the characteristics
      of JE, was related not only to the attachment to the tooth surface but also to
      changes of cell shape and cytoskeleton with stratification along the root
      surface.

PMID- 7562322
TI  - Assessment of alveolar bone loss with high resolution computed tomography.
AB  - In this in vitro study we compared high resolution computed tomography (HR-CT)
      with dental radiographs regarding the interpretation of horizontal and vertical
      alveolar bone loss. After removal of the soft tissue and metallic restorations of
      20 dentate upper and lower jaw segments 40 infra-alveolar bony defects of
      different dimensions were experimentally produced. The specimens were examined
      radiographically with standardized dental radiographs and 1.0 mm thick contiguous
      axial CT-scans. On the specimens, radiographs and CT-scans the bone loss was
      measured between the cemento-enamel junction and the adjacent alveolar bone level
      of 472 mesial and distal tooth surfaces; the identification, classification and
      vertical depth of the infra-alveolar bony defects were also compared. An average
      underestimation of 0.6 mm of horizontal alveolar bone loss in the dental
      radiographs and an overestimation of 0.2 mm in CT-scanning was shown. No
      significant differences between the imaging accuracy of horizontal alveolar bone
      loss between dental radiographs and CT-scanning could be evaluated. In the dental
      radiographs 24 (60%) of the infra-alveolar bony defects could be identified and
      the vertical depth was underestimated by a mean of 2.2 mm. In comparison, all 40
      (100%) infra-alveolar defects could be identified in the CT-scans and the
      vertical depth was underestimated by an average of 0.2 mm. The HR-CT-technique
      offers a three-dimensional interpretation of the alveolar morphology without
      overlying structures. This permits a high identification rate and classification
      of infra-alveolar bone loss according to the number of surrounding bone walls
      into one-, two or three-walled bony pockets.

PMID- 7562320
TI  - Characterisation of black-pigmented anaerobes isolated from diseased and healthy
      periodontal sites.
AB  - Prevotella intermedia has recently been re-defined and a new species, Prevotella
      nigrescens has been proposed. However, there is little data available on the
      incidence of these new species in periodontal health or disease. Black-pigmented
      anaerobes isolated from diseased and healthy subgingival sites were identified by
      serotyping, SDS-PAGE and physiological tests. In adult periodontitis subjects,
      64% of active sites, 35.7% of inactive sites and 38.5% of healthy sites yielded
      black-pigmented anaerobes. Of these, Porphyromonas gingivalis was found in 11% of
      active and 5% of healthy sites in diseased patients, Prevotella intermedia in
      15.5% of active and 20.5% of healthy sites, Prevotella nigrescens in 37.7% of
      active and 11.5% of healthy sites and Prevotella denticola in 3% of active and 1%
      of healthy sites. In healthy subjects, 50% of sites yielded black-pigmented
      anaerobes. P. gingivalis was not found in healthy subjects but P. intermedia was
      found in 18% and P. nigrescens in 31% of sites. SDS-PAGE proved to be a useful
      method for routinely differentiating P. intermedia and P. nigrescens and two sub
      types of the latter species were detected on the basis of band pattern. Only one
      P. nigrescens sub-type was found in any given individual and one type, typified
      by ATCC 25261, was more commonly found in deep pockets. However, overall both P.
      nigrescens and P. intermedia as species were just as frequently found at healthy
      sites as diseased sites. Thus, these species, in contrast to P. gingivalis,
      appear to be common commensals but they may act as opportunistic pathogens.

PMID- 7562321
TI  - Characteristics of multimodal co-aggregation between Fusobacterium nucleatum and
      streptococci.
AB  - The co-aggregation characteristics between Fusobacterium nucleatum and
      streptococci were examined to clarify the adherence factors participating in the
      co-aggregation. Nineteen strains of F. nucleatum were classified into 8 groups
      according to co-aggregation titer and inhibition by L-arginine, L-lysine and N
      acetyl-D-galactosamine (or lactose). The inhibition activity was, however, very
      different from strain to strain. With two fusobacterial strains, two inhibitors,
      which were both inhibition negative on their own, completely inhibited the co
      aggregation when used together in a mixture. In some co-aggregation pairs, the
      protease treatment of F. nucleatum inactivated one of the adherence factors, and
      resulted in the change of inhibition characteristics. These results indicate the
      multimodal co-aggregation of F. nucleatum with streptococci mediated by L
      arginine-sensitive, L-lysine-sensitive, N-acetyl-D-galactosamine-sensitive and in
      some resistant factors, and that the adherence factor or factors participating
      the co-aggregation change according to the co-aggregation partners.

PMID- 7562323
TI  - Effect of whole oral bacteria and extracted lipopolysaccharides on peripheral
      blood leukocyte interleukin-2 receptor expression.
AB  - Expression of the interleukin-2 receptor (IL-2R) on T cells is the molecular
      mechanism that initiates the G0 to G1 transition and is the critical first step
      for T cell proliferation in response to antigen. The effect of whole periodontal
      bacteria and lipopolysaccharides (LPS) on peripheral blood mononuclear cell
      (PBMC) IL-2R expression was examined in vitro. LPS induced a modest but
      significant increase in high affinity IL-2R alpha/beta (p55/p75 positive)
      expression on PBMC over untreated cells after 48 h culture. Addition of LPS to
      PBMC cultures depleted of monocytes had no effect on IL-2R expression compared to
      untreated cultures. Interleukin-1 (IL-1) caused a similar effect to LPS in 48 h
      PBMC cultures but IL-1 also increased high affinity IL-2R expression in cultures
      depleted of adherent mononuclear cells. When antibody to IL-1 was simultaneously
      added with LPS to PBMC cultures, the high affinity IL-2R inductive effect was
      reversed at 48 h, suggesting that the LPS effect on PBMC IL-2R was indirect, via
      monocytes. Whole pathogenic oral bacteria cultured with PBMC at high (100:1), but
      not low (10:1) bacteria:PBMC ratios had a similar effect to LPS, inducing high
      affinity IL-2R expression at 48 h. Increases in soluble IL-2R alpha were also
      measured in supernatants of PBMC incubated with periodontal bacteria compared to
      untreated controls. In this system, a critical threshold of bacteria was required
      to activate PBMC perhaps related to the quantity of cell-surface LPS presented to
      adherent mononuclear cells.

PMID- 7562324
TI  - Periodontal variables affecting nifedipine sequestration in gingival crevicular
      fluid.
AB  - We previously demonstrated the sequestration of nifedipine in gingival crevicular
      fluid (GCF), especially in patients exhibiting significant gingival overgrowth.
      The aim of the present study is to determine the role of site specific
      periodontal factors in this phenomenon. 10 adult patients exhibiting nifedipine
      induced gingival overgrowth were studied. In each patient GCF was harvested from
      two sites that demonstrated inflammation and increased probing depth as well as
      from two clinically healthy sites. The concentration of nifedipine was determined
      using gas chromatography. Drug concentrations were significantly increased in the
      presence of inflammation (p = 0.004) and plaque (p = 0.029) whilst increased
      probing depths and gingival overgrowth were not significantly related to drug
      sequestration. We can conclude that inflammatory changes in gingival tissues
      appear to be a significant determinant for the sequestration of nifedipine in the
      GCF.

PMID- 7562325
TI  - Inhibitory effects of a bisphosphonate (risedronate) on experimental
      periodontitis in rats.
AB  - The present study was designed to examine whether systemic administration of a
      bisphosphonate, risedronate, could prevent alveolar bone resorption in rats with
      experimental periodontitis. On Day 1, an elastic ring was placed around the neck
      of the right mandibular 1st molar to induce inflammatory periodontitis. The
      animals were given daily injections of either 0.9% NaCl (control group), or 0.8,
      1.6 or 3.2 mumoles/kg (s.c.) of risedronate (experimental groups) from Days 1 to
      7, and were killed on Day 8. Histological examinations and determination of bone
      mineral density in the interdental area between the 1st and 2nd molars with an
      image analyzer revealed that the presence of the elastic ring induced a loss of
      attachment and bone resorption in the control group. Vigorous bone resorption,
      with appearance of a large number of osteoclasts, was observed in the interdental
      and bifurcation areas. In the experimental groups, however, the resorption of
      alveolar bone and the loss of bone mineral content in these areas were prevented
      in a dose-dependent fashion, especially at doses of 1.6 and 3.2 mumoles/kg. Many
      osteoclasts were detached from the surface of the alveolar bone and had
      degenerated appearances, such as rounded shapes, loss of polarity and pyknosis.
      These results suggest that administration of risedronate is effective in
      preventing bone resorption in periodontitis.

PMID- 7562326
TI  - Time and position-specific expression of glycosaminoglycans in rat molar cementum
      related to physiological tooth movement.
AB  - The role of glycosaminoglycans (GAGs) and proteoglycans during cementogenesis is
      not known. In this study, we have analysed the temporal and spacial expression of
      GAGs in the cellular cementum of 10-30 weeks old rats, immunohistochemically
      using monoclonal antibodies 2B6 and 3B3, specific for chondroitin 4
      sulfate/dermatan sulfate and chondroitin 6-sulfate, respectively. Both 2B6- and
      3B3-epitopes were expressed at similar position and time in the rat cellular
      cementum. Two types of cellular cementum were identified; GAG-positive and GAG
      negative cementum. The former corresponded to the lightly stained and the latter
      to the darkly stained cementum in sections stained with haematoxylin and eosin.
      The GAG-positive cementum was seen at the distal side of dentine surface and
      appeared most thick at, middle of the apical half roots, whereas the other parts
      of the cementum were the GAG-negative. Distribution of GAG-positive cementum
      showed changes with age of animals. In 10-15 week old rats, the GAG-positive
      cementum occupied most of the cementum layer, covering a thin layer of the GAG
      negative cementum. The cellular cementum of 20-30 week old rats consisted of
      three layers; GAG-negative, GAG-positive and GAG-negative cementum from dentine
      to cementum surface, reducing the GAG-positive area. Because our previous study
      has demonstrated that the lightly stained cementum is uncalcified, the present
      result suggests a correlation between calcification and contents of GAGs in the
      cellular cementum. Further, time- and position-specific expression of GAGs
      indicates their relation to the physiological tooth movement, which has been
      known in the rat molars.

PMID- 7562327
TI  - In vitro activity of tetracyclines, macrolides, quinolones, clindamycin and
      metronidazole against periodontopathic bacteria.
AB  - We re-evaluated several antibiotics including newer ones, for their in vitro
      killing activity, as well as their inhibitory activity, against clinical isolates
      of periodontopathic bacteria. Tetracyclines were active against Porphyromonas
      gingivalis, and were highly active against Prevotella intermedia, but
      demonstrated only a low killing activity against Actinobacillus
      actinomycetemcomitans. Rokitamycin, a new macrolide, and clindamycin were highly
      active against P. gingivalis and P. intermedia, but showed very weak killing
      activity against A. actinomycetemcomitans. Quinolones demonstrated excellent
      bactericidal activity against A. actinomycetemcomitans, and good inhibitory and
      bactericidal activity against P. gingivalis and P. intermedia. Metronidazole had
      an activity almost equivalent to quinolones against P. gingivalis and P.
      intermedia; but it was the least active against A. actinomycetemcomitans.

PMID- 7562328
TI  - Studies on the angular reproducibility of positioning patients adjacent to an x
      ray tube. 2. A new electronically guided, force-sensitive sensor-based alignment
      system.

PMID- 7562329
TI  - Calibration of laser Doppler flowmetry for measurement of gingival blood flow.

PMID- 7562330
TI  - Loss of periodontal attachment in HIV-seropositive military personnel.
AB  - The cross-sectional relationship between severe loss of periodontal attachment
      (LPA) and worsening immune status due to HIV infection was evaluated in 474 HIV
      infected subjects (416 men, 58 women) aged 18 to 49 years who had been classified
      at stages 1 through 6 of the Walter Reed Army Institute of Research (WR) Staging
      Classification System. LPA was measured at four sites per tooth using a manual
      probe; severe LPA was defined as > or = 1 site/subject exhibiting > or = 5 mm
      LPA. Severe LPA was found in 94 (20%) of the subjects. Modeling with multiple
      logistic regression analysis revealed that WR stage and peripheral CD4+
      lymphocyte cell counts were not significant independent predictors of severe LPA.
      Severe LPA was more common in subjects at WR stage 5 or 6 who exhibited oral
      candidiasis (OC), a marker of immune system damage, than in persons at those WR
      stages without OC (odds ratio = 7.85; 95% confidence interval (CI) = 1.94-31.81).
      After the analysis controlled for WR stage, younger subjects receiving AZT had
      greater odds of severe LPA than same-age subjects not taking the drug (e.g., odds
      ratio for subjects aged 30 years = 2.59; 95% CI = 1.22, 5.49). Other significant
      predictors in the model included male sex; retired military status; cigarette
      smoking; and presence of cratered, ulcerated, or necrotic interdental papillae.
      HIV-associated immune deficiency may be associated with localized severe LPA, but
      this may be an indirect association due to medication use, opportunistic
      infection, or other factors not captured by the WR staging system or peripheral
      CD4+ cell counts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562332
TI  - Evaluation of the use of orthodontic records to measure the width of keratinized
      tissue.
AB  - Understanding the gingival tissue response in patients undergoing orthodontic
      treatment requires accurate pretreatment measurements of the width of the
      attached and keratinized tissue. Even though these may not be routinely recorded,
      it has been suggested that the orthodontic records can provide an accurate method
      of assessing the pretreatment keratinized tissue width. This clinical study was
      conducted to compare measures of the width of the keratinized tissue calculated
      from intraoral photographs and study models with direct clinical measures.
      Maxillary and mandibular study models and intraoral photographs were obtained
      from 33 patients. The width of the keratinized gingiva facial to the mandibular
      incisors was measured on two occasions to the nearest 0.5 mm. The width of the
      gingiva was calculated for the same teeth from two measures taken from projected
      photographic slides and the study models using a modification of Coatoam's
      technique. The method error was determined to be 0.43 mm for clinical measures
      and 0.32 mm for the calculated gingival tissue width. The reliability of
      measurement from orthodontic records was slightly greater than direct clinical
      measurement, with intraclass correlations of 0.93 and 0.90, respectively. The
      differences between the averaged clinical measure and averaged calculated measure
      for each tooth were small and not statistically significant (paired t-test, P =
      0.21, 0.66, 0.24, 0.24 for teeth 23 through 26 respectively). The results
      indicate that carefully taken photographic slides and study models can provide an
      accurate measure of keratinized tissue width.

PMID- 7562331
TI  - The functional interaction of EGF and PDGF with bradykinin in the proliferation
      of human gingival fibroblasts.
AB  - Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-BB are
      both involved in periodontal wound healing. Each of these growth factors exerts a
      positive proliferative effect on cells of the periodontium in vitro. However, in
      vivo the peptide bradykinin is one of a complex array of mediators present in
      addition to these growth factors. The purposes of this investigation were to: 1)
      evaluate bradykinin interactions with EGF and PDGF-BB altering cell proliferation
      in cultured human gingival fibroblasts (HGF), periodontal ligament cells (HPDL),
      and cells derived from alveolar bone (HOB); and 2) determine at the signal
      transduction level the mechanism of interaction between EGF and bradykinin in
      HGF. EGF and PDGF-BB stimulated DNA synthesis in a concentration-dependent
      manner, as measured by [3H] thymidine incorporation. Bradykinin alone did not
      alter significantly based DNA synthesis values; however, bradykinin in
      combination with EGF reduced DNA synthesis to nearly basal levels and bradykinin
      in combination with PDGF reduced the DNA synthesis over 50%. Examination of the
      interactions between bradykinin and EGF signal transduction pathways revealed
      that PGE2 release was increased in the presence of bradykinin and EGF (167 +/-
      33% to 317 +/- 29%). The bradykinin-stimulated PGE2 release was completely
      abolished by indomethacin. Indomethacin also was found to block the bradykinin
      inhibition of EGF-induced DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562333
TI  - Effects of toothbrushing prior and/or subsequent to dietary acid application on
      smear layer formation and the patency of dentinal tubules: an SEM study.
AB  - Dentine sensitivity is a quite common condition, associated with open dentinal
      tubules patent all the way to the pulp. The purpose of this in vitro study was to
      assess the effects of toothbrushing preceded and/or followed by dietary acid
      application on the patency of dentinal tubules. Dentine sections were prepared
      from recently extracted human molars and, after removal of the smear layer, were
      treated as follows: 1) toothbrushing alone; 2) toothbrushing followed by exposure
      to orange juice; and 3) toothbrushing subsequent to orange juice exposure. All
      specimens were observed in the scanning electron microscope (SEM) at a standard
      magnification and the patency of the dentinal tubules estimated. Results showed
      that toothbrushing alone was the most effective in occluding the tubules,
      followed by toothbrushing subsequent to dietary acid application, and then by
      toothbrushing prior to dietary acid application. From the results of this study
      it may be that in cases of dentine sensitivity toothbrushing should not precede
      or follow dietary acid application but be separate from mealtimes. Clinical
      research is required to confirm the findings of this in vitro study.

PMID- 7562334
TI  - The possible association between localized juvenile periodontitis and
      supernumerary teeth.
AB  - Supernumerary teeth and localized juvenile periodontitis in the same patient is a
      very unusual finding. Only 5 cases are reported, 2 of which were identical twins.
      An additional 2 cases are presented in which localized juvenile periodontitis was
      associated with multiple supernumerary premolars. These cases are strikingly
      similar to 3 of the previously reported cases, raising the possibility that this
      combination of disorders may be more than a chance association.

PMID- 7562335
TI  - Periodontal status and selected cultivable anaerobic microflora of insulin
      dependent juvenile diabetics.
AB  - The periodontal status and subgingival microflora of insulin-dependent juvenile
      diabetic (JD) patients (n = 16, mean age = 11.3) were compared with that of their
      non-diabetic cohabiting healthy siblings (HS, n = 16, mean age = 13.2). JD
      patients were monitored every 3 months for levels of glycosylated hemoglobin
      (HbA1c) and clinical and microbial parameters were measured 6 weeks before
      drawing blood for levels of HbA1c (M% = 8.76). Clinical indices, measured for the
      entire permanent dentition, included: probing depth (PD), attachment level (AL),
      sulcus bleeding index (SBI), and plaque index (PI). Subgingival plaque samples
      were obtained at 2 sites from each subject; whenever possible, the site with the
      deepest probing depth and the mesial aspect of the maxillary right first molar
      were used. Microbial analyses were determined by cultural characteristics and
      biochemical tests. No significant differences were detected in any of the
      clinical indices for the entire dentition. The mean AL for JD sites was 2.32 +/-
      0.83 mm and for HS sites was 2.2 +/- 0.85 mm. Mean percentage of total cultivable
      anaerobic microflora included Capnocytophaga spp. (JD, 13.21%; HS, 11%) and
      Porphyromonas gingivalis (JD, 5.1%; HS, 7.9%). Differences between the two groups
      were not statistically significant. When cluster analysis was performed on
      sampled sites, one cluster group in JD patients showed significantly elevated P.
      gingivalis and lower Capnocytophaga spp. levels as compared to the overall mean.
      The clinical parameters of this cluster were characterized by statistically
      significant greater loss of attachment and probing depth. These data would
      suggest few differences between JD patients and their HS in this population.

PMID- 7562336
TI  - Periodontal regeneration in class III furcation defects of beagle dogs using
      guided tissue regenerative therapy with platelet-derived growth factor.
AB  - We developed an effective regenerative therapy, referred to as platelet-derived
      growth factor-BB (PDGF-BB)-modulated guided tissue regenerative (GTR) therapy (P
      GTR), capable of achieving periodontal regeneration of horizontal (Class III)
      furcation defects in the beagle dog. To determine its efficacy, repair and
      regeneration of horizontal furcation defects by P-GTR therapy and GTR therapy
      were compared. Chronically inflamed horizontal furcation defects were created
      around the second (P2) and fourth mandibular premolars (P4). After
      demineralization of the root surfaces with citric acid, the surfaces of left P2
      and P4 were treated with PDGF-BB (P-GTR therapy) and those of contralateral teeth
      were treated with vehicle only (GTR therapy). Periodontal membranes were placed
      and retained 0.5 mm above the cemento-enamel junction for both groups. The
      mucoperiosteal flap was sutured in a coronal position and plaque control was
      achieved by daily irrigation with 2% chlorhexidine gluconate. At 5, 8, and 11
      weeks, two animals each were sacrificed by perfusion with 2.5% glutaraldehyde
      through the carotid arteries, and the lesions were sliced mesio-distally,
      demineralized, dehydrated, and embedded. Periodontal healing and regeneration
      after GTR and P-GTR therapy were compared by histomorphometric as well as
      morphological analysis. Morphometric analysis for each time period was performed
      on the pooled samples of P2 and P4. Five weeks after both therapies, the lesions
      were filled primarily by tissue-free area, epithelium, inflamed tissue, and a
      small amount of newly formed fibrous connective tissue. At 8 and 11 weeks after P
      GTR therapy, there was a statistically greater amount of bone and periodontal
      ligament formed in the lesions. The newly formed bone filled 80% of the lesion at
      8 weeks and 87% at 11 weeks with P-GTR therapy, compared to 14% of the lesion at
      8 weeks and 60% at 11 weeks with GTR therapy. Also, with P-GTR therapy there was
      less epithelium and tissue-free area, less inflamed tissue, and less connective
      tissue. Morphological analysis indicated that the defects around P2 revealed
      faster periodontal repair and regeneration than those around P4. While the
      lesions around P2 were effectively regenerated by 11 weeks even after GTR
      therapy, those around P4 failed to regenerate. On the other hand, P-GTR therapy
      further promoted periodontal repair and regeneration so that at 8 weeks the
      lesions around P2 and P4 demonstrated complete and nearly complete regeneration,
      respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562338
TI  - Interproximal free gingival grafts after membrane removal in guided tissue
      regeneration treatment of intrabony defects. A randomized controlled clinical
      trial.
AB  - The purpose of this controlled clinical trial was to compare the efficacy of two
      surgical approaches to protect the regenerated tissue following membrane removal
      in guided tissue regeneration (GTR) treated intrabony defects. Twenty-eight (28)
      defects, one each in 28 patients were randomly assigned after placement of the
      membrane to one of two treatment groups by blocking to prognostic variables. The
      test group received free gingival grafts on the interproximal regenerated tissue.
      In the control group the surgical flaps were coronally positioned over the
      regenerated tissue. The two groups were well balanced with respect to all
      prognostic variables. The results indicated that: 1) similar amounts of
      regenerated tissue were obtained in the two groups at membrane removal (7.6 +/-
      2.8 mm, test; 8.3 +/- 2.3 mm, control); 2) a significantly greater amount of
      probing attachment level gain was observed in the test group (5.0 +/- 2.1 mm,
      test; 3.7 +/- 2.1 mm, control). This study indicated that placement of free
      gingival grafts on the interdental regenerated tissue further improves the
      clinical outcome of GTR in deep intrabony defects.

PMID- 7562337
TI  - Commercially-prepared allograft material has biological activity in vitro.
AB  - The well-established finding that implantation of demineralized bone matrix at
      non-skeletal sites results in formation of cartilage and bone has been attributed
      to bone morphogenetic proteins/factors. Commercially-available demineralized bone
      allograft materials are being used currently to reconstruct/regenerate bone. The
      studies described here focused on establishing biological activity of protein
      extracts prepared from commercially obtained bone graft material in vitro.
      Furthermore, the biological activity of these protein extracts in vitro was
      compared with similar extracts prepared from freshly obtained human bone.
      Biological activities of bone matrix proteins examined included their ability to
      promote proliferation, attachment, and migration of gingival fibroblasts using an
      in vitro system. Guanidine followed by guanidine/EDTA was used to separate bone
      matrix proteins into proteins associated with soft tissues of bone and proteins
      retained within the mineral compartment, respectively. Two preparations of each
      starting material were tested and the biological activity of each preparation was
      evaluated in triplicate at least three times. Slot blot analysis revealed that
      commercially-prepared material contained type I collagen; fibronectin; BSP; and
      BMP-2, 4, and 7. However, the freshly prepared bone extracts appeared to have
      higher BMP concentrations. The ability of commercial extracts to promote cell
      proliferation, while significant, was limited and significantly less when
      compared with similar extracts prepared from freshly obtained bone. All extracts
      promoted cell attachment significantly, while none of the extracts promoted cell
      migration. Thus, commercially-prepared material retained proteins having the
      capacity to influence cell behavior in vivo. However, some biological activity as
      measured in vitro was lost as a result of tissue processing.

PMID- 7562339
TI  - Devices for dentoalveolar regeneration: an up-to-date literature review.
AB  - Regeneration of periodontal and alveolar ridge defects utilizing barrier
      membranes has become well established in clinical dentoalveolar reconstruction.
      Application of this technique has evolved from the concept of separating tissues
      during healing to that of providing a healing environment capable of regeneration
      of functional structures. The biomaterial characteristics and design of membranes
      employed in this technique play an important role in establishing and maintaining
      this environment. Barrier membranes must incorporate specific features that
      address the biological, mechanical, and clinical use requirements involved in
      regenerative treatment. Although nondegradable materials require a second
      surgical procedure for removal, these materials simplify certain aspects of
      development, production, and clinical regenerative treatment for some
      applications. Degradable materials introduce specific considerations and
      limitations regarding material selection, design, and clinical application. The
      progressive breakdown of degradable membranes results in dynamic changes in the
      mechanical and biocompatibility profiles of these materials. With present
      technology, these factors may limit use of degradable materials to specific
      applications. Membrane materials, therefore, should be selected based on a
      thorough understanding of the benefits and limitations inherent to the
      material(s) in relation to the functional requirements of specific clinical
      applications.

PMID- 7562340
TI  - The potential role of bone morphogenetic proteins in periodontal reconstruction.
AB  - Growth factors and cytokines are currently under investigation as potential
      therapeutics for the site-specific regeneration of alveolar bone. Many of these
      factors, including TGF-beta, PDGF, IGF-I, IGF-II, and FGF influence bone growth
      and resorption, and as such may be useful in the regeneration process. However,
      these molecules have effects on many other tissue and cell types. In contrast,
      the bone morphogenetic proteins (BMPs) represent a unique set of differentiation
      factors that induce new bone formation at the site of implantation instead of
      changing the growth rate of pre-existing bone. Recombinant human BMP-2 (rhBMP-2),
      for example, has been shown to induce ectopic bone formation in an in vivo
      setting. Cell culture studies indicate that rhBMP-2 can cause mesenchymal
      precursor cells to differentiate into cartilage- and bone-forming cells.
      Additional animal studies have shown that rhBMP-2 is capable of replacing large
      (2.5 cm) defects in canine mandibles, healing a variety of long bone defects in
      orthopedic animal models, and repairing bony defects in animal models of bone
      lost due to periodontal disease. These results suggest that rhBMP-2 has broad
      therapeutic potential for dental and cranio/maxillofacial reconstruction.

PMID- 7562341
TI  - Periodontal regenerative potential of space-providing expanded
      polytetrafluoroethylene membranes and recombinant human bone morphogenetic
      proteins.
AB  - A concept of space provision to support skeletal repair has long been used in
      orthopedic and oral maxillofacial reconstructive therapy. More recently, this
      concept has been studied and adapted to periodontal reconstructive therapy. Other
      studies have demonstrated that skeletal tissues represent a significant reservoir
      of growth factors, including bone morphogenetic proteins. Such factors have been
      shown to stimulate skeletal repair in preclinical models and in clinical defects.
      We herein review studies using the critical size supraalveolar periodontal defect
      model in which clinically meaningful periodontal regeneration was achieved
      following reconstructive surgery, including space provision by reinforced
      expanded polytetrafluoroethylene membranes or including surgical implantation of
      recombinant human bone morphogenetic protein-2. Potential mechanisms involved in
      observed regeneration are discussed.

PMID- 7562342
TI  - Platelet-derived growth factor-modulated guided tissue regenerative therapy.
AB  - The goal of this study was to develop an effective regenerative therapy capable
      of achieving periodontal regeneration of Class III furcation defects. We
      attempted to achieve this goal by combining three therapeutic approaches. First,
      the lesion was protected by an expanded polytetrafluoroethylene barrier membrane
      that prevents migration of gingival fibroblasts as well as osteogenic cells from
      the mucoperiosteal flaps. Second, platelet-derived growth factor-BB (PDGF-BB),
      which has potent chemotactic and mitogenic effects on periodontal ligament
      fibroblasts (PDL), was used to promote migration of fibroblasts and their
      proliferation on the root surface. Third, the root surface, demineralized by
      citric acid conditioning, was chosen as the primary site for PDGF-BB application.
      The demineralized root surface appeared to have the capability of providing a
      sustained release of the applied growth factor. This seemed to facilitate rapid
      repopulation of PDL fibroblasts on the root surface and new PDL formation in the
      early stages of repair, which contributed to complete periodontal regeneration
      without root resorption and ankylosis in later stages. Combining these
      approaches, we developed a therapy referred to as "PDGF-modulated guided tissue
      regenerative therapy." Unlike guided tissue regenerative therapy alone (without
      PDGF-BB), this therapy effectively promoted periodontal regeneration of Class III
      furcation defects in the beagle dog without significant ankylosis or root
      resorption.

PMID- 7562343
TI  - Commentary on periodontal diagnostic testing.

PMID- 7562344
TI  - Re: Comparison of DNA probe and ELISA microbial analysis methods and their
      association with adult periodontitis.

PMID- 7562345
TI  - The effects of intracanal medicaments, fillers, and sealers on the attachment of
      human gingival fibroblasts to an exposed dentin surface free of a smear layer.
AB  - To date there has been very little research into the possible effects of
      endodontic therapy on regeneration of the lost periodontal attachment. The
      objective of this study was to examine the effects of endodontic medicaments on
      fibroblast attachment to dentin surfaces free of a smear layer. Pulp chambers of
      extracted third molars were filled with one of the following medicaments: gutta
      percha with Roth's zinc oxide and eugenol-based sealer, warm gutta-percha with
      sealer, warm gutta-percha without sealer, calcium hydroxide, formocresol, cotton
      pellet, or left empty. A predetermined dentin surface area was then inoculated
      with human gingival fibroblasts at a concentration of 2 x 10(4) cells per ml. The
      cells were allowed to adhere to the dentin surface for either 4 or 24 hours, then
      cell attachment was quantified using a methyl-tetrazolium assay. The data were
      analyzed using a Kruskal-Wallis one-way analysis of variance and Dunn's multiple
      comparison test. It was determined that fibroblast attachment was significantly
      reduced when exposed to formocresol or warm gutta-percha without sealer at both
      the 4 and 24 hour interval (P < or = 0.05). This suggests that the use of
      formocresol or warm gutta-percha without sealer in a root canal may impede
      periodontal wound healing and regeneration.

PMID- 7562346
TI  - Growth factor effects on the expression of collagenase and TIMP-1 in periodontal
      ligament cells.
AB  - The fibroblast is a prominent cellular component of the periodontal ligament. It
      is believed to play an important role in collagen metabolism in health and
      disease. The turnover of collagen in the periodontal ligament is believed to be
      controlled by the balance between collagen synthesis and degradation. The family
      of matrix metalloproteinases and their inhibitors is one of the mechanisms which
      regulates this balance. The factors that regulate the synthesis of collagenase
      and its inhibitor, TIMP-1, by the periodontal ligament cell are poorly
      understood. The present study was undertaken to assess the effect of interleukin
      1 beta (IL-1 beta), platelet-derived growth factor (PDGF), and transforming
      growth factor-beta 1 (TGF-beta) on the expression of collagenase (MMP-1) and TIMP
      1 mRNA in periodontal derived fibroblasts using reverse transcription polymerase
      chain reaction (RT-PCR). Early passage periodontal ligament derived fibroblasts
      were treated with IL-1 beta (10 and 100 pg/ml), two isoforms of PDGF, -AA and -BB
      (4 and 20 ng/ml) and TGF-beta (1 and 10 ng/ml). Treatment with growth factors
      from 2 to 24 hours revealed that the largest effects on MMP-1 mRNA occurred after
      24 hours. IL-1 beta induced a 5 to 9 fold increase in MMP-1 mRNA. The two
      isoforms of PDGF had less of an effect (3 to 5 fold) on MMP-1 mRNA whereas TGF
      beta induced a 25 to 50% decrease in the expression of this message. None of the
      growth factors had an effect on TIMP-1 mRNA expression.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7562349
TI  - Prevalence of nifedipine-induced gingival hyperplasia.
AB  - This study investigated the prevalence of gingival hyperplasia in subjects who
      were undergoing treatment with a calcium channel blocker, nifedipine, in dentate
      and edentulous subjects. In addition, the relationship between gingival
      hyperplasia and 5 other variables (duration of nifedipine intake, dose, age, oral
      hygiene index, and number of teeth) was investigated. Results of statistical
      analyses showed overwhelming evidence that the percent of nifedipine subjects
      with gingival hyperplasia was greater than that of the control subjects (P <
      0.05) and that, across treatment group, the percent of dentate subjects with
      hyperplasia was significantly higher than that for edentulous subjects (P <
      0.05). The chi2 test showed a strong univariate relationship between gingival
      hyperplasia and, separately, oral hygiene and number of teeth. For 24% of the
      subjects with gingival hyperplasia index (GHI) values of 2 or 3, gingivectomy was
      performed, and the tissues were prepared for histological examination.
      Microscopic examination of the biopsy material showed findings similar to those
      from previously reported cases of nifedipine- or phenytoin-induced hyperplasia.

PMID- 7562347
TI  - Occurrence of certain bacterial species and morphotypes in juvenile periodontitis
      in Chile.
AB  - The occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia, Eikenella corrodens, Fusobacterium nucleatum,
      Campylobacter rectus, Capnocytophaga species, and certain bacterial morphotypes
      was determined in 18 affected and 18 unaffected sites in 10 localized juvenile
      periodontitis (LJP) patients, and in 10 affected and 10 unaffected sites in 5
      generalized juvenile periodontitis (GJP) patients. The subgingival proportion of
      the 7 bacterial species was determined by selective and nonselective culturing.
      The results showed that when considering the pure prevalence of bacteria ( > 0%)
      there were significant differences (P < 0.05) in the subgingival plaque
      microflora of the affected sites versus those of the unaffected sites for P.
      gingivalis, A. actinomycetemcomitans, P. intermedia, E. corrodens, C. rectus, and
      F. nucleatum in LJP, and for P. gingivalis, P. intermedia, and F. nucleatum in
      GJP. The mean proportions of cocci, motile rods and spirochetes were also
      significantly different (P < 0.05) in affected sites compared to unaffected
      sites. Capnocytophaga sp, F. nucleatum, P. intermedia, and E. corrodens were
      found in more than 75% of affected sites in LJP. When taking the approach that an
      organism, to be associated with periodontal disease, has to be detected above a
      certain minimum threshold, the results indicated that bacteria most frequently
      associated with LJP and GJP in Chile are P. gingivalis (66% of LJP and 80% of GJP
      affected sites), and A. actinomycetemcomitans (44% of LJP and 50% in GJP affected
      sites). Different bacterial species may be judged to be important in the disease
      process depending upon whether a pure bacterial prevalence, or a prevalence above
      a certain detection level, is considered.

PMID- 7562348
TI  - Clinical comparison of desired versus actual amount of surgical crown
      lengthening.
AB  - The actual length of clinically exposed tooth structure between planned
      restoration margin and alveolar crest ("biologic width") obtained during surgical
      crown elongation procedures was compared to the textbook goal of 3.0 mm. Sixteen
      (16) patients with 21 teeth requiring surgical crown lengthening for restoration
      placement participated. Oral hygiene instructions were given and optimal plaque
      control was mandatory. At each clinician's discretion, surgical techniques
      consisted of either gingivectomy or an apically positioned flap with and without
      osseous resection. Utilizing a reference stent, measurements were obtained at the
      facial, mesial-facial, lingual, and distal-lingual of the treated teeth both
      before and after osseous reduction. Parameters evaluated were gingival margin
      position, probing depth, mucogingival junction position, alveolar crest location,
      mobility, plaque index, and gingival index. These measurements were again
      recorded 8 weeks after surgery with the exception of alveolar crest. Statistical
      analysis with the paired t-test and linear correlation showed no significant
      change from baseline or among operators with varying experience in any of these
      parameters. Overall the results showed that the default objective of 3 mm between
      planned restoration margin and alveolar crest was not routinely achieved (mean
      2.4 +/- 1.4 mm). The post-treatment distance from the planned restoration margin
      to the alveolar crest was greatest at the facial aspect of the teeth (mean 2.6 +/
      1.2 mm) and least at the distal-lingual (mean 2.2 +/- 1.7 mm). In addition,
      although more experienced periodontists removed a larger amount of bone, the
      amount of root surface exposed was still short of the initially desired biologic
      width.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562351
TI  - Dose-dependent gingival overgrowth induced by cyclosporin in rats.
AB  - This study evaluated the effect of dosage on severity of cyclosporin-A (CSA)
      induced gingival overgrowth. Eighty (80) male Sprague-Dawley rats were randomly
      distributed into 4 groups. Rats in each group daily received CSA in mineral oil
      by gastric feeding at dosages of 0 (control), 3, 10, and 30 mg/kg, respectively,
      for 6 weeks. Stone models of the mandibular incisal region were obtained biweekly
      and were used for analysis of the gingival dimensions. Animals were sacrificed at
      the end of week 6 and tissue sections were processed for histopathologic
      evaluations. Animals were sacrificed at the end of week 6 and tissue sections
      were processed for histopathologic evaluation Gingival overgrowth including bucco
      lingual and mesio-distal width and vertical height were significantly increased
      with increasing CSA dosage. Furthermore, the gingival dimensions displayed a
      positive linear relation to dosage and treatment duration. The histopathologic
      evaluation revealed a granulomatous tissue wedging the tooth-gingival interface
      in the 3 mg/kg group. This tissue had reached exuberant size in the 10 and 30
      mg/kg groups. In summary, the analysis of gingival dimensions the histopathologic
      evaluation shows a dose-dependent effect on the severity of CSA-induced gingival
      overgrowth.

PMID- 7562350
TI  - Immunohistochemical expression of extracellular matrix components of normal and
      healing periodontal tissues in the beagle dog.
AB  - Periodontal regeneration requires formation of periodontal tissues lost due to
      periodontal disease. To better understand the formation of new periodontal
      tissues during periodontal repair and regeneration, immunohistochemical
      expression of extracellular matrix components of normal as well as healing
      periodontal tissues was evaluated and compared using the avidin-biotin complex
      immunohistochemical technique. For this purpose, horizontal furcation defects
      were created around mandibular P2 and P4 of 6 dogs after extraction of P1 and P3.
      The root surfaces were conditioned with citric acid and expanded
      polytetrafluoroethylene (ePTFE) membranes were placed and retained 0.5 mm above
      the cemento-enamel junction. The mucoperiosteal flaps were sutured in a coronal
      position. Two animals were sacrificed at 2, 4, and 8 weeks, and mesio-distal
      tissue slices containing normal or healing periodontal tissues were
      demineralized, dehydrated, and embedded in paraffin. Immunohistochemical
      localization of type I collagen (CI), fibronectin (FN), secreted protein, acidic
      and rich in cysteine (SPARC), vitronectin (VN), and bone sialoprotein (BSP) was
      performed on 6 microns thick sections. Morphological results demonstrated that at
      2 weeks after defect creation, lesions were filled primarily with granulation
      tissue which was gradually replaced by newly-formed fibrous connective tissue,
      periodontal ligament (PDL), cementum, and bone between 4 and 8 weeks. The results
      of immunohistochemical study revealed that at 2 weeks the granulation tissue,
      especially in the intercellular spaces of inflammatory cells, was intensively
      stained for FN and VN. At 4 and 8 weeks, staining for CI, FN, and VN was found in
      fibrous connective tissue, the newly-formed PDL, cementum, and osteoid. Further
      the attachment zone of the PDL collagen fibers to cementum showed intense
      staining for FN. Immunostaining for SPARC was positive in the new PDL, cementum,
      and bone, while staining for BSP was restricted to the new cementum and bone.
      Interestingly, the PDL, especially in areas adjacent to active bone formation,
      demonstrated intense staining for BSP. However, fibrous connective tissue and PDL
      proper were unstained for BSP. These results indicate that FN and VN are involved
      in the early stages of periodontal repair, and periodontal regeneration is
      achieved through formation of periodontal tissues that are composed of different
      matrix components specific to different types of periodontal tissues.

PMID- 7562352
TI  - Planning for the manpower needs for the next generation of periodontal patients.
AB  - Projections by the bureau of the census indicate that there will be an additional
      55.6 million people 20 years and older living in this country by the year 2020.
      Estimates are developed for each state and region of the needed numbers of
      periodontists to maintain current practitioner levels. The availability of needed
      practitioners is considered in terms of the number of graduates from periodontal
      training programs. A short-fall is projected in the number of training program
      graduates needed to maintain current periodontist-to-population ratios by 2020.

PMID- 7562353
TI  - The influence of the design of two different bioresorbable barriers on the
      results of guided tissue regeneration therapy. An intra-individual comparative
      study in the monkey.
AB  - The aim of the present study was to compare two bioresorbable barriers to
      evaluate whether differences in design influence the result of guided tissue
      regeneration (GTR) therapy. Twenty-four (24) plaque exposed, recession type
      defects in 4 monkeys were treated. Contralateral defects were randomized for test
      or control treatment. During a healing period of 6 weeks, gingival recession
      resulting in device exposure occurred at 3 test and 10 control sites. One control
      barrier was exfoliated. Histologically, 9 of the 12 test barriers were completely
      integrated with the surrounding tissues. At 3 test sites, epithelium had migrated
      apically outside the barrier to a level not exceeding one-third of the height of
      the device. Seven of the 11 control barriers were enclosed by dentogingival
      epithelium. The adjacent connective tissue exhibited local inflammatory cell
      infiltrates (ICT). At the remaining 4 control sites, the epithelial downgrowth as
      well as the adjacent ICT areas were limited to the coronal 1/3 of the device. New
      attachment; i.e., new cementum with inserting collagen fibers, averaged 2.2 mm
      and 0.8 mm at the test and control sites respectively (P < 0.01). Based on the
      results of the present study, it was concluded that a bioresorbable GTR device,
      designed to prevent epithelial downgrowth along the barrier surface, has a higher
      potential to promote new attachment formation than a device which does not have
      this property.

PMID- 7562355
TI  - Treatment of class II furcation involvements in humans with bioresorbable and
      nonresorbable guided tissue regeneration barriers. A randomized multi-center
      study.
AB  - In this multi-center study 38 patients with contralateral molar Class II
      furcation defects were treated with GTR therapy using a bioresorbable matrix
      barrier (test) and a nonresorbable expanded polytetrafluoroethylene (ePTFE)
      barrier (control). Following flap elevation, scaling, root planing, and removal
      of granulation tissue, each device was adjusted to cover the furcation defect.
      The flaps were repositioned and sutured to complete coverage of the barriers. A
      second surgical procedure was performed at control sites after 4 to 6 weeks to
      remove the nonresorbable barrier. Before treatment and 12 months postsurgery all
      patients were examined and probing depths, clinical attachment levels, and
      position of the gingival margin were recorded. The primary response variable was
      the change in clinical attachment level in a horizontal direction (CAL-H change).
      Both treatment procedures reduced the probing depths (P < or = 0.001).
      Statistically significant gain of clinical attachment level in both horizontal
      and vertical direction was found at the test sites. At control sites gain of
      attachment in horizontal direction was statistically significant. The gain of CAL
      H was 2.2 mm at test sites compared to 1.4 mm at control sites (P < or = 0.05).
      At test sites, the gingival margin was maintained close to the pre-surgical level
      (0.3 mm), whereas at control sites gingival recession was evident (0.9 mm), the
      difference being statistically significant (P < or = 0.01). Postsurgical
      complications, such as swelling and pain were more frequent following the control
      treatment (P < or = 0.05).

PMID- 7562354
TI  - The effect of initial periodontal therapy on salivary platelet-activating factor
      levels in chronic adult periodontitis.
AB  - Platelet-activating factor (PAF), a potent phospholipid inflammatory mediator, is
      increased in the mixed saliva of subjects with periodontal disease and correlates
      with the extent of oral inflammation. The present study was designed to provide a
      longitudinal evaluation of the effect of initial periodontal therapy (home care
      instruction, prophylaxis, and scaling/root planing) on salivary PAF levels in
      chronic adult periodontitis patients (n = 15). Mixed saliva was collected prior
      to, during, and after initial therapy and was utilized to assess PAF levels after
      lipid extraction and fractionation as well as to histologically assess the number
      of polymorphonuclear leukocytes (PMN). PAF activity was determined in bioassay
      relative to authentic PAF (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine;
      16:0-alkyl-PAF). Initial salivary PAF levels (12.1 +/- 2.8 pmole equivalents of
      16:0-alkyl-PAF/ml saliva; mean +/- SE) decreased following supragingival plaque
      control (9.6 +/- 2.4) and were further reduced following scaling and root planing
      (5.7 +/- 1.4). In parallel, salivary PMN levels were significantly reduced and
      clinical estimates of periodontal disease were significantly improved; i.e.,
      there was a decrease in the percentage of sites with both bleeding on probing
      (from 46.1 +/- 4.6% of sites at pretreatment to 25.9 +/- 2.6% after scaling and
      root planing) and probing depths > or = 4 mm (from 16.7 +/- 1.9% of sites to 10.3
      +/- 1.2%). Thus, initial periodontal therapy reduced salivary PAF levels in
      concert with improvements in clinical estimates of marginal and submarginal
      periodontal inflammation suggesting that PAF may participate in inflammatory
      events during periodontal tissue injury and disease.

PMID- 7562356
TI  - Treatment of intrabony defects with collagen membrane barriers. Case reports.
AB  - Two separate investigations were undertaken to assess the clinical
      characteristics and the safety, and to determine whether an absorbable type 1
      bovine collagen barrier membrane would result in the improvement of clinical
      parameters during guided tissue regeneration in humans. The collagen membrane
      barrier was placed over a total of 21 interdental intrabony periodontal defects
      in 18 patients. The surgical procedures and postsurgical regimen were similar in
      both components of the investigation. Sulcular incisions were used and the sites
      were surgically exposed by reflection of full thickness mucoperiosteal flaps. The
      intrabony defects were debrided and the root surfaces prepared with automatic
      scalers and curets. Four 1-minute applications of tetracycline HCl 50 mg/ml were
      applied to the root surface. The collagen membrane barrier was hydrated in
      sterile saline until pliable, then trimmed so it covered the osseous defect and
      extended 2 to 3 mm beyond the defect. In both investigations, the collagen
      barrier membrane was not sutured, but retained by "pouching" or undermining the
      flap. Healing occurred without complications. There were no untoward or adverse
      reactions to the material in either phase of the study. In the initial
      investigation, 13 intrabony defects with probing depths of > or = 5 mm were
      treated in 9 patients having a mean age of 50.6 years. No controls defects were
      treated. Soft and hard tissue measurements were taken at the time of initial
      surgery and at 2, 4, and 6 months. In the second phase, 9 patients were enrolled
      with a mean age of 49.7 years. They had similar bilateral interdental intrabony
      defects with probing depths > or = 6 mm. One defect received the collagen
      membrane barrier, while the other was treated by flap debridement alone. The
      collagen membrane had undergone modification since the initial investigation, and
      was more highly cross-linked to retard absorption. After initial therapy, and
      prior to the surgical procedure, a series of 3 dermal patch tests were used to
      determine whether the patient would elicit a reaction to the collagen. Venous
      blood was drawn at baseline, 7 to 10 days, 18 to 21 days and at 8 weeks for
      analysis by ELISA for comparison of test and control sites relative to baseline.
      There were no allergic response to the dermal tests, and the ELISA tests
      indicated no significant differences between test and control sites. An automated
      probe was used to record soft and hard tissue measurements. These included the
      probing depths and clinical attachment levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562357
TI  - Treatment of an endodontic perforation with a restoration and a root coverage
      gingival graft.
AB  - This case report describes the treatment of a perforation on the facial surface
      of the maxillary right central incisor made during endodontic therapy. Treatment
      of this highly visible area required a creative approach to therapy. The
      perforation was repaired with an amalgam restoration. A connective tissue with
      partial thickness double pedicle graft was used to replace missing periodontal
      structures, cover the exposed root surface, and obscure from view, as much as
      possible, the amalgam restoration placed in the perforation. This unconventional
      therapy is offered as a possible treatment option when few or no other acceptable
      options exist.

PMID- 7562358
TI  - Occurrence of Actinobacillus actinomycetemcomitans and anti-leukotoxin antibodies
      in some members of an extended family affected by Papillon-Lefevre syndrome.
AB  - Eighteen (18) members of an extended family in which numerous individuals have
      Papillon-Lefevre syndrome (PLS) were examined. In all, 6 affected members and 12
      non-affected members were included. All patients underwent a clinical examination
      which, in the dentate persons, included plaque index, bleeding on probing,
      probing depth, and periodontal attachment loss and a set of full mouth periapical
      x-rays. Subgingival bacterial samples were also collected from 2 teeth in the
      dentate patients for cultures and identification of Actinobacillus
      actinomycetemcomitans. Serum samples were collected from all participants and
      assayed for antileukotoxin antibodies. The results indicate that there is a high
      prevalence of leukotoxic strains of A. actinomycetemcomitans in persons suffering
      from PLS, as well as in unaffected family members. The ubiquitous presence of A.
      actinomycetemcomitans in the family units suggests a close association between A.
      actinomycetemcomitans and the periodontal disease associated with the syndrome;
      it also suggests that A. actinomycetemcomitans by itself is not sufficient for
      the expression of periodontal disease and that other factors, some of which must
      be genetic, are necessary for lesion development.

PMID- 7562359
TI  - Levels and domains in personality: an introduction.
AB  - This special issue is centered around the problem of levels and domains in
      personality functioning. What kind of constructs--and at what levels and in what
      domains--are needed to understand what a person is like? To account for the
      complexity and scope of human lives, personality psychologists have traditionally
      put forth lists and taxonomies of factors, features, and variables that must be
      taken into consideration in formulating an adequate psychological portrait of the
      whole person. The five-factor model of personality traits has recently been
      offered as a comprehensive framework; however, critical analyses of the trait
      concept have revealed the limitations of a trait-based model of personality.
      Recognizing that the concept of trait is indispensable to a vital psychology of
      personality, this special issue aims to (a) communicate recent developments and
      organizational frameworks for understanding the person at multiple levels and in
      varied domains, and (b) articulate and elaborate units of analysis that, when
      combined with trait assessments, yield a psychology of personality that is
      commensurate with the complexity of individual functioning and that offers
      greater potential for the attainment of the original goals of the discipline.

PMID- 7562361
TI  - Seeing one's self: locating narrative memory in a framework of personality.
AB  - Individuals confront the continuing challenge of attending to the competing
      demands of internal and external stimuli. The emerging I-Self applies three
      principles of evaluation, categorization, and subsidiation to organize these
      informational demands. These principles guide the development of the five systems
      of personality--cognition, affect, motivation, behavior, and psychophysiology.
      These systems interact to create various Me-Selves that comprise the different
      roles and contexts of the personality. Each Me-Self contains evaluations
      (valenced responses to self and others), categories (self- and other
      representations), and sequences in time (the self and others in past, present,
      and future). Narrative is the perceptual expression of a particular Me-Self in
      consciousness. Narrative memory allows for meaningful analysis by consciousness
      of specific Me-Selves and the cognitions, affects, and goals associated with
      those selves. Applications of this position to research and psychotherapy are
      discussed.

PMID- 7562360
TI  - Psychological needs and the facilitation of integrative processes.
AB  - The assumption that there are innate integrative or actualizing tendencies
      underlying personality and social development is reexamined. Rather than viewing
      such processes as either nonexistent or as automatic, I argue that they are
      dynamic and dependent upon social-contextual supports pertaining to basic human
      psychological needs. To develop this viewpoint, I conceptually link the notion of
      integrative tendencies to specific developmental processes, namely intrinsic
      motivation; internalization; and emotional integration. These processes are then
      shown to be facilitated by conditions that fulfill psychological needs for
      autonomy, competence, and relatedness, and forestalled within contexts that
      frustrate these needs. Interactions between psychological needs and contextual
      supports account, in part, for the domain and situational specificity of
      motivation, experience, and relative integration. The meaning of psychological
      needs (vs. wants) is directly considered, as are the relations between concepts
      of integration and autonomy and those of independence, individualism, efficacy,
      and cognitive models of "multiple selves."

PMID- 7562362
TI  - The system-topics framework and the structural arrangement of systems within and
      around personality.
AB  - The field of personality psychology possesses rich theories and excellent
      research, but few good means to communicate them. The system-topics framework is
      an integratory approach that divides the study of personality into three central
      topics and their subdivisions: (a) the components of personality, (b) the
      organization of those components, and (c) the development of those components and
      their organization over time. The present article describes the system-topics
      framework and then examines the addition of a potential new topic useful to an
      improved exposition of the field: the structural arrangement of the component
      systems in and around personality. A three-dimensional model of these systems is
      created that can synthesize the many spatial metaphors used in earlier
      personality theory and research. The reasons for integrating this structural
      model within the system-topics framework and how such integration can be
      accomplished are discussed.

PMID- 7562363
TI  - A clinical-empirical model of personality: life after the Mischelian ice age and
      the NEO-lithic era.
AB  - A theory of personality should lead to both accurate prediction and interpretive
      understanding. Aside from its empirical uses, a personality theory should provide
      a grammar that allows personality psychologists to infer meaning from overt
      behavior with more sophistication than a layperson, and the best laboratory for
      testing the interpretive utility of a personality theory remains the clinic. With
      respect to the appropriate data for constructing and evaluating theories of
      personality, an overreliance on questionnaire data is problematic for several
      reasons: It assumes that understanding people requires no training, it mistakes
      research on the conscious self-concept for research on personality, it conflates
      implicit and explicit knowledge, it fails to address defensive biases, and it
      lacks interrater reliability. Consideration of both empirical and clinical data
      points to three questions that define the elements of personality necessary for a
      comprehensive assessment of an individual: (a) What psychological resources-
      cognitive, affective, and behavioral dispositions--does the individual have at
      his or her disposal? (b) What does the person wish for, fear, and value, and how
      do these motives combine and conflict? (c) How does the person experience the
      self and others, and to what extent can the individual enter into intimate
      relationships?

PMID- 7562364
TI  - Juxtaposed scripts, traits, and the dynamics of personality.
AB  - Although personality is theoretically composed of multiple facets that function
      in lively interrelatedness, the interplay among these multiplicities has mostly
      been missed by research that focuses on traits as the primary unit of
      personality. The juxtaposition of contrary interpersonal scripts is a promising
      way to capture dynamic processes of personality. A case study is used to
      illustrate the dynamic interplay between sociotropic (extraverted) and avoidant
      scripts. Whereas standard trait measures do not reveal how extraversion and
      avoidance co-relate in everyday experience, the dynamics are revealed by study of
      interpersonal scripts in narratives of memorable encounters. Similarities between
      the present approach and recent dialectical approaches to the self-concept are
      discussed (Hermans & Kempen, 1993). Such approaches, particularly when
      articulated so as to interface with more generalized units of personality, can be
      highly useful for advancing understanding of personality dynamics.

PMID- 7562365
TI  - Multiple identities and the integration of personality.
AB  - Life-history interviews show narrators to shift among multiple, often
      contradictory self-representations. This article outlines a model that accounts
      for how a relatively small set of self-symbols and metaphors can form a grammar
      like system that simultaneously defines and integrates multiple identities.
      Drawing on generative theories from linguistics, anthropology, and music, the
      model proposes that this system provides a unitary deep structure that can be
      configured in various arrangements to yield multiple surface structures. Each
      "surface" identity constructs an individual's emotions and social relations--and
      what he or she accepts as "Me" and rejects as "not-Me"--into a distinct pattern,
      with identity per se appearing as a dialogic or fugue-like structure of opposed
      voices. Study-of-lives interviews conducted by the author in urban America and
      rural Morocco are used to present the model and to demonstrate the pivotal role
      played by multistable or "structurally ambiguous" symbols in anchoring reversible
      self-representations which integrate personality as a system of organized
      contraction. The musical analogy is emphasized in order to build a bridge toward
      current research in cognitive science and toward efforts to formulate a "state
      integration" theory of personality development.

PMID- 7562366
TI  - Self-with-other representations and a taxonomy of motives: two approaches to
      studying persons.
AB  - This article discusses two approaches to studying persons. Part 1 describes data
      gathering procedures that lead to an integrated visual display of particular self
      representations of an individual in various spheres of life. "Self-with-other
      representation" is introduced as a central unit of analysis in this research.
      This concept is integrated into a method that is exemplified in this article by a
      description of how life can be injected into static trait characterization of a
      person. In the context of a case study, it is shown that the method provides
      information about how traits are organized in terms of self-with-other working
      models and the conditions under which a particular working model is likely to
      prevail. Part 2 presents a new taxonomy of motives. This taxonomy is a product of
      having dipped into the area of operant conditioning and reformulating behavioral
      consequences into motivational causes. This intrusion into reinforcement theory
      has resulted in a two-dimensional classification system (referred to as PACK)
      that accounts for motives to keep or acquire positive experiences, and to cure or
      prevent negative experiences. After the taxonomy is described, it is used to
      organize motivational concepts in the area of goal-directed behaviors, and it is
      applied to purpose statements of individuals in different age groups.

PMID- 7562367
TI  - A multifactorial approach to the study of gender characteristics.
AB  - The present article reviews some of the central conceptual issues confronted by
      gender researchers as they have tried to forge a theory of gender identity that
      can account for the complexity and diversity of gender-related characteristics
      displayed by women and men. An emerging consensus suggests that gender is
      incorporated into an individual's self-concept in multiple and loosely connected
      ways. We review one example of this emerging multiplicity perspective, Spence's
      (1993) multifactorial gender identity theory, and describe three recent studies
      testing its usefulness. We also discuss ways in which multiplicity models of
      gender could benefit from considering parallel developments in the general
      personality literature regarding the problem of levels or domains. In particular,
      it is argued that McAdams's (this issue) integrative three-level model of the
      structure of personality offers a helpful framework for guiding future test
      construction and theory development in gender research.

PMID- 7562368
TI  - Immunomodulatory role of melatonin: specific binding sites in human and rodent
      lymphoid cells.
AB  - This paper reviews the evidence that supports the hypothesis of the existence of
      specific binding sites for melatonin on immune cells. These binding sites have
      been described in human blood lymphocytes and granulocytes, and thymus, spleen,
      and bursa of Fabricius from different rodents and birds. The dissociation
      constant values of these binding sites are in the 0.1-1 nM range, suggesting that
      melatonin may play a physiological role in lymphocyte regulation. Moreover,
      melatonin binding sites appear to be modulated by guanine nucleotides. Therefore,
      in addition to other mechanisms described for the regulation of immune function
      by melatonin, a direct mechanism of regulation can be involved via binding of
      melatonin by immunocompetent cells.

PMID- 7562370
TI  - Distinct modes of melatonin secretion in normal men.
AB  - As for many hormones, melatonin levels in the blood suggest that it is discharged
      from the pineal gland in a pulsatile manner. Recently, the existence of short
      term episodes, superimposed on the circadian pattern of circulating melatonin,
      has been questioned. Because plasma melatonin levels reflect not only the
      secretory process, but also the effects of distribution and degradation,
      secretory rates were estimated from peripheral levels, using a deconvolution
      procedure. Fourteen healthy volunteers were studied during the night, while
      sleeping in the dark (2300-0700), and seven of them subsequently were used in a
      replicate study. Plasma melatonin levels were measured at 10-min intervals by a
      direct, specific radioimmunoassay. Pulse analysis was performed using the
      computer program ULTRA. Approximately 30% more pulses were detected on the
      overall secretory were often superimposed on tonic basal secretion. Their number,
      amplitude, and distribution over time were variable depending on subjects. Also
      the mean melatonin secretory rate varied more than threefold across individuals.
      Despite the large interindividual variability, the subjects, who were used in
      replicate experiment, displayed a rather similar secretory profile. We conclude
      that in normal adult men, melatonin secretion undergoes two distinct secretory
      modes, in which episodic secretion is superimposed on tonic secretion in subject
      dependent variable proportions.

PMID- 7562372
TI  - Effects of photoperiod on pineal melatonin in the marsh rice rat (Oryzomys
      palustris).
AB  - Pineal melatonin content was examined under four different photoperiods (10L:14D,
      12L:12D, 14L:10D, and 16L:8D) in adult female rice rats (Experiment 1). Pineal
      melatonin was basal during the light and increased beginning 1 hr after lights
      off. Within 2 hr after lights off, melatonin increased to levels that were
      maintained throughout the dark period. In all but one photoperiod (10L:14D),
      melatonin remained elevated prior to light onset and decreased markedly within
      one hour after lights on. In addition, the duration of pineal melatonin was
      inversely related to the length of the photoperiod. In Experiment 2, the time
      course of pineal melatonin content on 16L:8D was examined every 20 min during the
      first hour after lights off and the first hour after lights on. Melatonin content
      increased gradually during the first hour and decreased markedly within 20 min
      after lights on. These data show that pineal melatonin in female rice rats is
      regulated by photoperiod.

PMID- 7562371
TI  - Melatonin and cortisol assessment of circadian shifts in astronauts before
      flight.
AB  - Melatonin and cortisol were measured in saliva and urine samples to assess the
      effectiveness of a 7-day protocol combining bright-light exposure with sleep
      shifting in eliciting a 12-hr phase-shift delay in eight U.S. Space Shuttle
      astronauts before launch. Baseline acrophases for 15 control subjects with normal
      sleep-wake cycles were as follows: cortisol (saliva) at 0700 (0730 in urine);
      melatonin (saliva) at 0130 (6-hydroxymelatonin sulfate at 0230 in urine).
      Acrophases of the astronaut group fell within 2.5 hr of these values before the
      treatment protocols were begun. During the bright-light and sleep-shifting
      treatments, both absolute melatonin production and melatonin rhythmicity were
      diminished during the first 3 treatment days; total daily cortisol levels
      remained constant throughout the treatment. By the fourth to sixth day of the 7
      day protocol, seven of the eight crew members showed phase delays in all four
      measures that fell within 2 hr of the expected 11- to 12-hr shift. Although
      cortisol and melatonin rhythms each corresponded with the phase shift, the
      rhythms in these two hormones did not correspond with each other during the
      transition.

PMID- 7562369
TI  - Calbindin-D28k, calretinin, and S-100 immunoreactivities in rat pineal gland
      during postnatal development.
AB  - Profound morphological modifications occur during postnatal development of the
      rat pineal gland. We have immunohistochemically followed those events from
      postnatal day 1 to 20 by using three cytoarchitectonic markers (S-100, calbindin
      D28k, and calretinin) that belong to the calmodulin/troponin C calcium-binding
      protein family. In the developing rat pineal, anticalbindin-D28k antibody labels
      three cell types: immature and mature astrocytes and perivascular type II
      pinealocytes. During development, calbindin-D28k positive cells migrate from the
      base of the pineal stalk into the superficial part of the pineal. Calbindin-D28k,
      usually used as a neuronal marker in the central nervous system, recognizes in
      rat pineal precursor astrocytes 5 days before S-100 and labels a subpopulation
      somewhat different from S-100 positive astrocytes. Calretinin immunoreactivity
      appeared in the postero-superior part of the pineal and was abundant until
      postnatal day 5, then its density dramatically felt to leave, after postnatal day
      20, an occasional population of cells whose morphology is compatible with neuron
      like cells.

PMID- 7562373
TI  - Seasonal changes in the levels of antidiuretic hormone and melatonin in the
      elderly.
AB  - Antidiuretic hormone (ADH) and melatonin in plasma were measured every 4 hr
      during a 24-hr period in 69 elderly volunteers (42 males and 27 females) aged
      75.6 +/- 8.8 years (+/- SD) and 73.5 +/- 9.5 years, respectively. The population
      was divided into three groups, which were examined February 27-28, April 25-26,
      and November 14-15. For the males, the mean ADH level during 24 hr was lowest in
      April and highest in November with a level five times higher than in April. The
      ADH level in February was about three times higher that in April. Females did not
      show any seasonal variation in the ADH system. The melatonin levels were lowest
      in November, higher in February, and even higher in April in both male and female
      volunteers. The ADH increased with age in males (R2 = 0.13; P < 0.05) but not in
      females (R2 = 0.07; NS). The melatonin concentration decreased with age for the
      whole group, aged 60-98 years.

PMID- 7562374
TI  - Low and high melatonin excretors among healthy individuals.
AB  - To meet the need of establishing firm normative data regarding the
      secretion/excretion of human melatonin, nighttime urinary melatonin of 16 healthy
      volunteers was measured in samples collected monthly over a period of 1 year. Low
      melatonin excretors (N = 8) were distinguished from high melatonin excretors (N =
      8), based on a cut-off mean melatonin value of 0.25 nmol/l. There was no overlap
      in any of the monthly melatonin values between the two groups, while their annual
      rhythms of melatonin excretion were not different in shape. Since no obvious
      factors (age, sex, height, weight, etc.) were responsible for the observed
      differences, the distinction between low and high nocturnal excretion and by
      inference secretion of melatonin most likely reflects genetically determined
      variable levels of the noradrenergic secretory drive and/or variable N
      acetyltransferase/hydroxyindole-O-methyltransferase enzymatic activity during the
      night.

PMID- 7562375
TI  - Day-night changes in melatonin levels in different organs of the cricket (Gryllus
      bimaculatus).
AB  - Day-night levels of melatonin (N-acetyl-5-methoxytryptamine) were determined in
      different organs of adult female crickets (Gryllus bimaculatus) exposed to a
      12/12 light/dark cycle, using reversed-phase high performance liquid
      chromatography coupled with fluorometric detection. Melatonin levels in the
      compound eye, brain, and palp were significantly higher during the dark period
      than during the light period, suggesting that a diurnal rhythm of melatonin
      levels exists in these organs of crickets, with a peak during the dark period.
      Conversely, melatonin levels were significantly higher during the light period
      than the dark period in the cercus, ovipositor, antenna, hind-leg and ovary. No
      significant day-night difference was found in the fore- and mid-legs, Malpighian
      tube, and digestive tube. Thus, these organs may have different melatonin
      metabolizing systems compared to those found in the compound eye, brain, and
      palp. Differences in the phasing of the melatonin rhythm in various organs of the
      cricket suggest possible differences in melatonin function in these organs.

PMID- 7562376
TI  - Knowing and doing when the times are uncertain.

PMID- 7562377
TI  - Evolution of parental stress and coping processes: a framework for critical care
      practice.
AB  - Crisis theory, stress and coping theory, and research on parental stress and
      coping during pediatric critical care experiences are integrated into a
      conceptual framework for understanding, assessing, and ultimately intervening to
      reduce parental stress and bolster coping. Within this framework, cognitive
      appraisal of stress, coping and person and situation factors are discussed as
      important determinants of parents' adaptation to this stressful situation. The
      nurse's ability to respond to the evolving nature of parental stress and coping
      processes over the course of the experience enhances the use of the framework in
      designing coping interventions.

PMID- 7562378
TI  - Life-threatening situations: supporting the child survivor and the family.
AB  - Children encounter life-threatening situations through trauma as well as acute
      and chronic illnesses. These life-threatening situations are not only potentially
      physically incapacitating but also emotionally scarring. Using Jillings' model
      for life-threatening illnesses, nurses are able to assess and intervene with
      child survivors and their families to insure optimum psychological and emotional
      outcomes.

PMID- 7562379
TI  - Spiritual care of the school-age child with a chronic condition.
AB  - Chronic conditions present many challenges to the school-age child and the family
      that may create physical, psychosocial, and spiritual disruptions. The spiritual
      well-being of the child and family greatly influences coping and condition
      management. Therefore, spiritual assessment becomes an integral part of nursing
      care for these families. A case study describes the spirituality of the school
      age child and the family within the context of having a chronic condition.
      Therapeutic play, bibliotherapy, and use of self are discussed, using the nursing
      process, as strategies to meet the spiritual needs of child and family.

PMID- 7562380
TI  - Nursing management of children with sickle cell disease: an update.
AB  - This article reviews current trends in managing children with sickle cell disease
      (SCD). The pathophysiology, medical and nursing management, and complications of
      SCD are discussed. Current trends and research findings related to improving the
      prognosis of children with SCD are offered. The importance of the nurse's role in
      educating the family about the disease process and clinical interventions to
      prevent or manage complications are stressed. Lastly, a nursing care plan is
      offered which focuses on pertinent nursing diagnosis.

PMID- 7562381
TI  - Compensatory parenting: how mothers describe parenting their 3-year-old,
      prematurely born children.
AB  - Premature infants and their mothers experience difficulties in establishing their
      relationships. The effect of these early problems on later parenting is not
      known. This study explored whether mothers' recollections surrounding the birth
      and hospitalization of a preterm infant affected their perceptions and their
      parenting of these children at 3 years of age. Twenty-seven primary caregivers of
      30 prematurely born children completed three questionnaires on their perceptions
      of their children and were interviewed about parenting experiences. The core
      concept identified in analysis was compensatory parenting, a parenting style in
      which mothers provided special experiences and avoided others in an attempt to
      compensate the children for their neonatal experiences. Compensatory parenting
      was influenced by the view of these prematurely born children as both special and
      normal and by salient prenatal, labor, and delivery experiences; memories of the
      neonatal intensive care unit experience; the sequelae of emotional responses to
      these experiences; and subsequent health problems after discharge. Prospective
      research is needed to further study compensatory parenting and to develop
      interventions.

PMID- 7562382
TI  - Maternal responsiveness of socially high-risk mothers to the elicitation cues of
      their 7-month-old infants.
AB  - This descriptive study of 19 socially high-risk mother-infant dyads in
      naturalistic interaction focused on maternal response to infant elicitation cues.
      Maternal response behavior was coded on a continuum from underresponsive to
      adequate to overresponsive. Maternal affect was rated separately using selected
      items from an existing scale. As a whole, the maternal sample was emotionally
      depressed and largely underresponsive to infant cues. When placed by maternal
      response into adequate, overresponsive, and underresponsive subgroups, adequate
      mothers more often responded appropriately to infant cues, were never physically
      unavailable to their infants, showed no anxiety, and were more positively
      responsive to their infants' smiles and cries. Adequate mothers scored higher in
      all affective areas. Maternal depression was associated with both overresponse
      and underresponse. Angry maternal mood was significantly related to
      underresponse. Considerable maternal strength lies in this high-risk sample and
      could be the basis for therapeutic intervention to normalize parenting.

PMID- 7562383
TI  - Bright futures.

PMID- 7562384
TI  - Use of the Zaadi Doll to provide health education to children and families.

PMID- 7562385
TI  - Meeting patients' needs for educational materials.

PMID- 7562386
TI  - Childhood diarrhea and malnutrition in Pakistan, Part III: Social policy issues.

PMID- 7562387
TI  - The dissection of selection in person perception: inhibitory processes in social
      stereotyping.
AB  - Although people simultaneously belong to multiple social categories, any one of
      these competing representations can dominate the categorization process. It is
      surprising therefore to learn that only a few studies have considered the
      question of how people are categorized when multiple categorizations are
      available. In addition, relatively little is known about the cognitive mechanisms
      through which these categorization effects are realized. In the reported
      research, we attempted to extend recent ideas from work on selective attention to
      shed some light on these fundamental issues in social perception. Our basic
      contention was that following the initial identification of a person's applicable
      categories, the categorization process is driven by the interplay of both
      excitatory and inhibitory mechanisms. The results of 3 studies supported this
      contention. We discuss our findings in the wider context of contemporary issues
      in social stereotyping.

PMID- 7562388
TI  - Attitude strength and resistance processes.
AB  - This study examined whether multiple indicators of attitude strength form general
      dimensions that foster differential pathways to resistance. Ego involvement,
      certainty, personal importance, knowledge, and extremity were assessed.
      Resistance processes and outcomes were measured in a selective judgment paradigm.
      Intentions to act on attitudes and information-seeking proclivities were also
      assessed. Factor analysis of the strength measures revealed 2 factors. Both
      fostered intentions to act but were associated with differential resistance
      processes and outcomes. Heightened levels of the factor representing Commitment
      to one's position were associated with increased selective elaboration, selective
      judgment, and attitude polarization. Embeddedness, the linkage of the attitude to
      one's self-concept, value system, and knowledge structure, was associated with
      decreased selective elaboration and increased information seeking and selective
      memory.

PMID- 7562389
TI  - Savings in relearning: II. On the formation of behavior-based trait associations
      and inferences.
AB  - Five experiments based on Carlston and Skowronski's (1994) relearning paradigm
      suggest that people spontaneously derive trait knowledge about actors from
      behaviors but that this knowledge may reflect either explicit trait inference
      processes or implicit actor-trait associations. Experiments 1 and 2 found that
      inference-instructed and control Ss showed equivalent savings in subsequent
      efforts to learn actor-trait pairs but not when instructed Ss initially inferred
      the wrong trait. Experiment 3 showed that savings were equivalent for stimuli
      from different sources, and Experiment 4 showed that savings effects persisted
      even when the target was only incidentally associated with a stimulus behavior.
      Finally, Experiment 5 suggests that after several days, even explicit trait
      inferences can become inaccessible to intentional retrieval, although the earlier
      experiments show that they continue to exert an implicit effect on learning.

PMID- 7562390
TI  - Desensitization and resensitization to violence against women: effects of
      exposure to sexually violent films on judgments of domestic violence victims.
AB  - An experiment was conducted to examine the effects of repeated exposure to
      sexually violent films on emotional desensitization and callousness toward
      domestic abuse victims. Results indicated that emotional response, self-reported
      physiological arousal, and ratings of the extent to which the films were sexually
      violent all diminished with repeated film exposure. Three days following exposure
      to the final film, experimental participants expressed significantly less
      sympathy for domestic violence victims, and rated their injuries as less severe,
      than did a no-exposure comparison group. Five days after the final film exposure,
      their level of sensitivity to the domestic violence victims had rebounded to
      baseline levels established by the comparison group. Emotional responsiveness at
      the final film exposure was correlated with levels of sensitivity to the domestic
      violence victims 3 days later but not at subsequent observation points.

PMID- 7562392
TI  - Predicting young adults' health risk behavior.
AB  - A prototype model of risk behavior is described and was tested in a longitudinal
      study of 679 college students, beginning at the start of their freshman year.
      Perceptions of the prototype associated with 4 health risk behaviors (smoking,
      drinking, reckless driving, and ineffective contraception) were assessed along
      with self-reports of the same behaviors. Results indicated that prototype
      perception was related to risk behavior in both a reactive and a prospective
      manner. That is, perceptions changed as a function of change in behavior, and
      perceptions predicted those behavior changes as well. This prospective relation
      was moderated by social comparison, as the link between perception and behavior
      change was stronger among persons who reported frequently engaging in social
      comparison.

PMID- 7562393
TI  - Social evaluation and cardiovascular response: an active coping approach.
AB  - Cardiovascular effects of social evaluation were examined under different task
      conditions. In Experiment 1, systolic responses in women were greater under
      public than private conditions when a fixed behavioral challenge was difficult,
      but not when the challenge was easy. In Experiment 2, social evaluation
      potentiated systolic responsivity in men and women when a behavioral challenge
      was unfixed, but not when a behavioral challenge was fixed and easy to meet.
      Results are discussed in terms of a recent integrative analysis of effort and
      cardiovascular response as well as alternative conceptions that posit, or might
      be taken to imply, an association between publicity and physiologic activation.

PMID- 7562391
TI  - Stereotypes and ethnocentrism: diverging interethnic perceptions of African
      American and white American youth.
AB  - Much recent work on stereotyping has dealt with groups that are either
      artificially created or that do not have an extensive history of conflict. The
      authors attempted to overcome this limitation by examining issues of perceived
      variability and ethnocentrism among samples of White American and African
      American youth. The goals were both to examine theoretical issues in stereotyping
      and to describe the current state of ethnic interrelations among young people.
      Four studies are reported. Throughout, the samples of African Americans
      demonstrate interethnic judgments that are consistent with existing work on
      stereotyping and ethnocentrism. White American students, however, reported
      judgements that replicate neither the out-group homogeneity effect nor
      ethnocentrism. Alternative explanations for this difference are considered, and
      the discussion focuses on differing views concerning the role of ethnic identity
      and diversity in our society.

PMID- 7562394
TI  - Identity in three cohorts of midlife women.
AB  - To study similarities and differences in personality across historical periods,
      ego identity patterns, assessed by Q-sort prototypes, were compared in
      longitudinal samples of midlife women who had been young adults in the 1950s,
      early 1960s, and late 1960s. Identity pattern had similar relationships across
      sample with vector dimensions of the California Psychological Inventory but was
      related to work and family outcomes only in the younger cohorts, whose lives were
      less restricted. Women with the achieved-foreclosed pattern were more alike
      across cohort than women with the achieved-moratorium pattern. Among the latter,
      independence and high aspirations were salient salient features of the younger
      cohorts, whereas interest in motives of self and others were salient in the older
      cohort.

PMID- 7562395
TI  - The intersection of life stage and social events: personality and life outcomes.
AB  - Two studies examined the intersection of life stage with the experience of social
      events. Study 1 tested whether social events coinciding with early adulthood are
      more meaningful to individuals than events during other life stages (K. Mannheim,
      1972; A. J. Stewart & J. M. Healy, 1989). In 4 of 5 samples of college-educated
      women (3 age cohorts), the hypothesis was supported. Study 2 examined the impact
      of the women's movement on the personalities and careers of women who experienced
      the movement during early adulthood versus early middle adulthood. Women in both
      cohorts who found the movement meaningful attained higher education, work status,
      and income levels; were employed in upwardly mobile careers; and were more
      assertive and self-confident at midlife than women who found the movement less
      important. Consistent with hypotheses, finding the women's movement meaningful
      was associated with personality change in the older cohort.

PMID- 7562396
TI  - [Basic study and application of functional liposomes].
AB  - Liposomes are the models of biomembranes and are new thought to be ideal tools in
      the field of drug delivery system. Liposomalization of various drugs has been
      revealed to enhance their efficacy and to reduce the side effect of the drugs.
      For the site-specific delivery, intracellular targeting, and controlled release
      of drugs, many functional liposomes have been developed based on their natures as
      the models of biomembranes. In this report, the preparation and characterization
      of functional liposomes are discussed. At first, the hydration process of lipids
      which is an important step for the liposomal preparation was discussed. Secondly,
      three kinds of functional liposomes were presented, namely, thermosensitive
      liposomes for delivering macromolecules, pH-sensitive liposomes for the cytosolic
      delivery of encapsulated materials, and reticuloendothelial system (RES)-avoiding
      liposomes for the passive targeting to tumor tissues. Finally, the actual
      usefulness of RES-avoiding liposomes modified with a uronic acid derivative,
      palmityl-D-glucuronide for the tumor imaging and therapy was demonstrated.

PMID- 7562398
TI  - [Mechanism of resistance to antitumor agents--its involvement in blood-brain
      barrier].
AB  - Resistance of tumors to a variety of chemotherapeutic agents presents a major
      problem in cancer treatment. The gene responsible for multidrug resistance,
      termed mdr1, encodes a membrane glycoprotein (P-glycoprotein) that acts as a pump
      to transport various cytotoxic agents. The P-glycoprotein has been shown to bind
      anticancer drugs and several resistance-reversing agents including calcium
      channel blockers, and to be an ATPase. The P-glycoprotein was found to function
      in the blood-brain barrier. The physiological function of the P-glycoprotein in
      relation to therapy is discussed.

PMID- 7562397
TI  - [Nerve growth factor strategy and preparation of animal model for Alzheimer-type
      senile dementia].
AB  - Nerve growth factor (NGF) plays an important role in the survival and maintenance
      of cholinergic neurons in the central nervous system. In senile dementia of the
      Alzheimer type (SDAT), learning and memory are impaired by the loss of neurons in
      the magnocellular cholinergic neuronal system. It is, therefore, of interest to
      investigate the role of NGF in this degenerative disorder. Since NGF does not
      cross the blood-brain barrier and is easily metabolized by peptidases when
      administered peripherally, it can be used for medical treatment only when
      directly injected into the brain. We tried to develop drugs which could be taken
      orally and stimulate the NGF synthesis in the brain. In addition, we attempted to
      develop a SDAT animal model using osmotic minipump to infuse beta-amyloid protein
      into cerebral ventricle, since there are no SDAT model animals accompanied with
      various pathophysiological changes. We demonstrate here that the oral
      administration of propentofylline, idebenone and trimethylquinone derivative,
      potent in vitro NGF synthesis stimulators, induced the increase in NGF protein
      and mRNA, and in choline acetyltransferase activity, in basal forebrain-lesioned
      and aged rats, but not in intact young rats. These drugs also ameliorated the
      behavioral deficits in habituation, water maze, and passive avoidance tasks in
      these animals. These results suggest that these drugs stimulated NGF synthesis in
      vivo and ameliorated the behavioral deficits which were accompanied with the
      reduced choline acetyltransferase activity in the basal forebrain-lesioned and
      aged rats. In terms of the SDAT animal model, the performance of the water maze
      and passive avoidance tasks was impaired and choline acetyltransferase activity
      significantly decreased in beta-amyloid protein-treated rats. Histochemical
      results showed the deposition of beta-amyloid protein in the cortex and
      hippocampus and atrophy and loss of hippocampal neurons. These results suggest
      that the deposition of beta-amyloid protein in the brain is related to the
      impairment of learning and cholinergic neuronal degeneration, and that beta
      amyloid protein-treated rats could be an animal model for SDAT and used for the
      screening of drugs for SDAT.

PMID- 7562399
TI  - [Serum 1-methyladenosine and pseudouridine as tumor markers in tumor-bearing
      mice].
AB  - It is known that in cancer patients elevated levels of modified nucleosides
      originated from RNA are excreted in the urine. Modified nucleosides in the serum
      are thought to be more useful than those in the urine as tumor markers because
      they are not influenced by other factors. However the determination of these
      nucleosides is difficult because of their low amounts. To examine the efficacy of
      the modified nucleosides in the serum as tumor markers, ascites and solid tumor
      mouse models were prepared, and the amounts of 1-methyladenosine and
      pseudouridine in the serum were determined. Along with the growth of ascites
      tumor, the amounts of 1-methyladenosine and pseudouridine in the serum increased.
      The modified nucleosides in the serum in a solid tumor model also increased. This
      is the first report on the variation in the amount of 1-methyladenosine in the
      serum of tumor models, and the results suggest the usefulness of measuring the
      amounts of 1-methyladenosine and pseudouridine in the serum as tumor markers.

PMID- 7562400
TI  - [Activation of retinoic acid (RA)-differentiated HL-60 cells by saponins].
AB  - The effect of saponins on the one of major functions of neutrophil, namely the
      generation of superoxide anion (O2-), was investigated using retinoic acid (RA)
      differentiated HL-60 cells (promyelocytic leukemia cells). The generation of O2-
      from the cells induced by saponins was monitored by the reduction of cytochrome
      c. All five species of crude saponins studied here, i.e. tea-leaf saponins, tea
      seed saponins, ginsenosides, soyasaponins and saikosaponins, stimulated the
      generation of O2- from RA-differentiated HL-60 cells. Tea-leaf saponins showed
      the highest stimulating activity, followed by soyasaponins and ginsenosides. The
      cytotoxic activity of saponins was determined by the dye exclusion method after
      the incubation of RA-differentiated HL-60 cells with various concentrations of
      saponins. Saikosaponins and tea-seed saponins exhibited considerable cytotoxic
      activity and hemolytic activity. To examine the involvement of protein kinase C
      (PKC) in the neutrophil activation by saponins, the effect of H-7, an antagonist
      of PKC, on the generation of O2- induced by saponins was investigated. H-7 was
      found to inhibit the generation of O2- in a dose-dependent manner, suggesting the
      participation of PKC in the neutrophil stimulating process by saponins. Tea-leaf
      saponins, ginsenosides and soyasaponins, which had high neutrophil stimulating
      activity and low cytotoxic activity, seemed to be useful as a biological response
      modifier (BRM) for the activation of neutrophil.

PMID- 7562401
TI  - [Participation of sialic acid residue in the fibrinogen-fibrin conversion by
      thrombin].
AB  - In order to estimate the effects of sialic acid residues in fibrinogen on the
      fibrinogen-fibrin conversion by bovine thrombin the Michaelis constant (Km) and
      maximum velocity (Vmax) were determined. The Km value obtained by the use of
      intact-fibrinogen was smaller than that of asialo-fibrinogen. This fact suggests
      that the sialic acid residues affected the formation of the enzyme-substrate
      complex. It was also found that in comparison with the asialo-fibrinogen, the
      intact-fibrinogen was significantly influenced in the gel formation time by the
      ionic strength in the reaction solution.

PMID- 7562402
TI  - Formulation factors affecting release of drug from topical vehicles. II. Effect
      of solubility on in vitro delivery of a series of n-alkyl p-aminobenzoates.
AB  - The major influence on the rate of drug transfer out of its vehicle and into the
      skin is the thermodynamic activity of the drug within its formulation. This study
      addresses certain thermodynamic dependencies of topical delivery in a model
      system. Prototypical water-in-oil (W/O) and oil-in-water (O/W) emulsions and
      their component phases are used as the test vehicles, polydimethylsiloxane is the
      membrane, and three homologous n-alkyl p-aminobenzenzoate esters are the test
      permeants. In an emulsion, the interaction of the compound between the water and
      oil phase can determine the extent of lowering of the thermodynamic activity in
      the external phase in contact with the membrane. The emulsifiers (surfactants)
      impact strongly on partitioning and permeation as a result of the extra
      solubilizing capacity contributed by the surfactant micelles. The lower flux in
      the aqueous phase of the O/W emulsion is the result of micellar solubilization,
      and this solubilization increased with increasing ester chain length.
      Solubilization is also an influence in nonaqueous phases, but permeant
      hydrophobicity is without specific influence; therefore, transport become less
      dependent upon the structure of the compound.

PMID- 7562403
TI  - Budesonide-beta-D-glucuronide: a potential prodrug for treatment of ulcerative
      colitis.
AB  - Budesonide-beta-D-glucuronide is a potentially useful orally administered prodrug
      for the treatment of colonic inflammatory bowel disease. Budesonide is a
      topically active glucocorticosteroid that exhibits low oral bioavailability (15%)
      in humans and laboratory animals. Oral delivery of budesonide to the inflamed
      tissues of the large intestine as its glucuronide prodrug should lead to locally
      high concentrations of active drug. Following liberation and absorption of the
      active drug, a large portion should be inactivated due to hepatic metabolism.
      Budesonide-beta-D-glucuronide was chemically stable in solutions at pHs of 1.5,
      4.5, 6.5, and 7.4 at 37 degrees C. The enzymatic lability of the prodrug was
      assessed in luminal contents and mucosa obtained from conventional, germ-free,
      and colitic rats under in vitro conditions. There was a substantial change in
      glycosidase activity between the small intestine (proximal and distal portions)
      and the cecum in both conventional and colitic rat luminal contents. Luminal
      hydrolytic activity was low along the entire rat gastrointestinal tract of germ
      free rats. Mucosal glycosidase activity was relatively low along the entire
      gastrointestinal tract of all three types of rats. The hydrolysis of prodrugs
      budesonide-beta-D-glucuronide and dexamethasone-beta-D-glucuronide in human fecal
      samples from patients with ulcerative colitis and normal volunteers was also
      measured. There were no statistically significant differences between the normal
      and colitic fecal samples for hydrolysis of the either prodrug or between the
      relative rates of hydrolysis of the two prodrugs. Hydrolysis rates of the
      prodrugs were about two orders of magnitude less in human fecal samples compared
      with those in cecal and colonic contents from the rat.

PMID- 7562404
TI  - Absorption characteristics of chemically modified-insulin derivatives with
      various fatty acids in the small and large intestine.
AB  - Absorption characteristics of insulin derivatives chemically modified with
      various fatty acids in the intestine were determined by in situ loop and in vitro
      modified Ussing chamber methods. The pharmacological activities of these acyl
      derivatives, as assessed by their hypoglycemic effects after intravenous
      administration, were reduced upon increasing the carbon number of the fatty
      acid(s) chemically attached to native insulin. However, high pharmacological
      activities were seen when mono-and dicaproyl derivatives were administered
      intravenously. The absorption of insulin after its small intestinal
      administration could be hardly improved by acylation. In contrast, its absorption
      after the large intestinal administration was increased by increasing the number
      of caproic acid molecules attached to insulin. Furthermore, by an in vitro
      modified Ussing chamber method, it was revealed that the permeability of insulin
      across both the duodenal and colonic mucous membranes was also improved by
      increasing the number of caproic acid molecules. These in situ and in vitro
      results indicated that the chemical modification of insulin with fatty acids was
      a useful approach for improving insulin absorption from the large intestine.

PMID- 7562405
TI  - Penetration of minoxidil from ethanol/propylene glycol solutions: effect of
      application volume and occlusion.
AB  - We have previously established that the relative concentrations of propylene
      glycol and ethanol as a binary solvent system have a significant effect on the
      skin penetration of 2% solutions of minoxidil at 50 microL/cm2. The present work
      extends these studies and investigates the penetration of minoxidil from the
      different vehicle combinations as functions of application volume and occlusion.
      Decreasing the application volume has a variable effect which depends on vehicle
      composition. Penetration of minoxidil from 100% ethanol solutions decreased
      linearly with application volume. Generally, irrespective of the volume applied,
      the penetration of minoxidil increased with increasing ethanol fraction with a
      maximum penetration at 90% ethanol. Penetration from all the formulations was
      enhanced upon occluding the skin, with greatest increase evident in solutions
      with higher volatile fraction. Penetration of minoxidil in vivo showed trends
      similar to those seen in vitro.

PMID- 7562406
TI  - Physicochemical characterization of a new respirable form of nedocromil.
AB  - Elongated, respirable particles of nedocromil were prepared by its
      crystallization from N-methyl-2-pyrrolidone (NMP) obtained from an aqueous
      solution of its sodium salt by precipitation with hydrochloric acid. Aerosols of
      these particles were recently generated and characterized for their aerodynamic
      properties (Chan, H.-K.; Gonda, I. J. Aerosol Med. 1993, 6, 241-249). This paper
      reports the physiochemical properties of the solid form of nedocromil as
      characterized by polarizing optical and scanning electron microscopies, thermal
      analysis (DSC, TGA), X-ray powder diffraction, water vapor adsorption isotherms,
      mass spectrometry, solid state Fourier transform IR and solution 1H-NMR
      spectroscopies.

PMID- 7562407
TI  - A mechanistic study of ultrasonically-enhanced transdermal drug delivery.
AB  - Although ultrasound has been shown to enhance the transdermal transport of a
      variety of drugs, the mechanisms underlying this phenomenon are not clearly
      understood. In this paper, we evaluate the roles played by various ultrasound
      related phenomena, including cavitation, thermal effects, generation of
      convective velocities, and mechanical effects, in the ultrasonic enhancement of
      transdermal drug delivery (sonophoresis). Our experimental findings suggest that
      among all the ultrasound-related phenomena evaluated, cavitation plays the
      dominant role in sonophoresis using therapeutic ultrasound (frequency range, 1-3
      MHz; intensity range, 0-2 W/cm2). Furthermore, confocal microscopy results
      indicate that cavitation occurs in the keratinocytes of the stratum corneum upon
      ultrasound exposure. It is hypothesized that oscillations of the cavitation
      bubbles induce disorder in the stratum corneum lipid bilayers, thereby enhancing
      transdermal transport. Evidence supporting this hypothesis is presented using
      skin electrical resistance measurements. Finally, a theoretical model is
      developed to predict the effect of ultrasound on the transdermal transport of
      drugs. The model predicts that sonophoretic enhancement depends most directly on
      the passive permeant diffusion coefficient, rather than on the permeability
      coefficient through the skin. Specifically, permeants passively diffusing through
      the skin at a relatively slow rate are expected to be preferentially enhanced by
      ultrasound. The experimentally measured sonophoretic transdermal transport
      enhancement for seven permeants, including estradiol, testosterone, progesterone,
      corticosterone, benzene, butanol, and caffeine, agree quantitatively with the
      model predictions. These experimental and theoretical findings provide
      quantitative guidelines for estimating the efficacy of sonophoresis in enhancing
      transdermal drug delivery.

PMID- 7562408
TI  - Thermally induced denaturation of lyophilized bovine somatotropin and lysozyme as
      impacted by moisture and excipients.
AB  - The endothermic thermal transitions (i.e., denaturation) of lyophilized
      recombinant bovine somatotropin (rbSt) and lysozyme as seen via differential
      scanning calorimetry were evaluated with respect to moisture and excipients. The
      denaturation temperature, Tm, of rbSt and lysozyme decreased with increasing
      moisture irrespective of the excipient. However, the magnitude of the decrease
      elicited by moisture was dependent on the type of excipient. Furthermore, the
      effect of the excipient was dependent on the moisture content; excipients
      decreased Tm in low moisture solids (i.e., < 5% moisture) and increased it in
      hydrated solids (i.e., > 15% moisture). In the dry state (< 1% moisture), the
      addition of 50% sucrose, sorbitol, or glycerol lowered the Tm of rbSt from 161
      degrees C to 136, 120, and 83 degrees C, respectively, indicating a destabilizing
      mechanism. Likewise, the Tm of lysozyme decreased from 156 degrees C to 142, 128,
      and 97 degrees C due to the addition of sucrose, sorbitol, and glycerol,
      respectively. At higher moisture contents, the excipients promoted a higher
      transition temperature at a given moisture content than the pure protein systems,
      indicating a stabilizing mechanism. An increase in the enthalpy of unfolding for
      dehydrated lysozyme was noted with increasing levels of moisture and/or
      excipient, despite the observed decrease in Tm. The thermal stability, or Tm, of
      the dehydrated proteins appeared to be correlated to the glass transition
      temperature (Tg) of the excipient, which in turn should be related to the Tg of
      the system. The lower the Tg of the excipient, the greater was the degree of
      destabilization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562409
TI  - Effect of surfactants on the physical stability of recombinant human growth
      hormone.
AB  - The physical stability of a human growth hormone (hGH) formulation upon exposure
      to air/water interfaces (with vortex mixing) and to nonisothermal stress
      [determined by differential scanning calorimetry (DSC)] was investigated. The
      effect of these stresses on the formation of soluble and insoluble aggregates was
      studied. The aggregates were characterized and quantified by size exclusion-HPLC
      and UV spectrophotometry. Vortex mixing of hGH solutions (0.5 mg/mL) in phosphate
      buffer, pH 7.4, for just 1 min caused 67% of the drug to precipitate as insoluble
      aggregates. These aggregates were noncovalent in nature. Non-ionic surfactants
      prevented the interfacially induced aggregation at their critical micelle
      concentration (cmc) for Pluronic F-68 (polyoxyethylene polyoxypropylene block
      polymer) and Brij 35 (polyoxyethylene alkyl ether) and above the cmc for Tween 80
      (polyoxyethylene sorbitan monooleate). However, the same surfactants failed to
      stabilize hGH against thermal stress in DSC studies. Higher concentrations of
      surfactants actually destabilized hGH as evidenced by the decrease in the onset
      temperature for the denaturation endotherm.

PMID- 7562410
TI  - Enhanced potency of human calcitonin when fibrillation is avoided.
AB  - The peptide hormone calcitonin (CT) is a potent drug for the therapy of different
      bone diseases. Salmon CT (sCT) is reported to be more active than human CT (hCT).
      Human CT, but not sCT, has a strong tendency to aggregate and fibrillate in
      aqueous solutions. Recent investigations of the fibrillation mechanisms
      contributed to the development of hCT solutions in which fibrillation is
      inhibited. Taking into consideration these new findings, we tested the relative
      activities of hCT handled so as to avoid aggregation/fibrillation, sCT handled in
      exactly the same way, and hCT handled carefully but without regard to possible
      fibrillation (denoted R-hCT). The effect of the CTs on bone resorption by
      isolated osteoclasts was measured. This assay measures the activity of interest
      (bone resorption) by the cell (the osteoclast) at which therapy is directed. The
      concentration that inhibits 50% of resorption (EC50) for hCT is 10(-5)-10(-4)
      pg/mL, compared with 10(-2)-1 pg/mL for R-hCT and 10(-3)-10(-1) pg/mL for sCT.
      The results show that when aggregation and fibrillation are avoided, hCT at the
      EC50 is 2-4 orders of magnitude more active than R-hCT. Thus, earlier reports of
      lower potency of hCT compared with sCT may have been based on inadvertent use of
      partially aggregated/fibrillated samples of hCT. This finding may have
      implications for the dose and dosage forms advised for human therapy.

PMID- 7562411
TI  - Self-association of dexverapamil in aqueous solution.
AB  - The pKa and intrinsic solubility of monomeric dexverapamil were determined from
      its pH-solubility profile to be 8.90 and 6.6 x 10(-5) M, respectively. The
      solubility of dexverapamil below pH 7.0 was higher than expected on the basis of
      the aforementioned values. This unusually high solubility is believed to be due
      to the self-association of cationic dexverapamil. The apparent pKa of the self
      associated drug is estimated to be approximately 7.99. The self-association of
      dexverapamil hydrochloride is supported by the fact that it is surface active and
      that it increases the solubility of both naphthalene and anthracene in aqueous
      solutions. The dependence of the drug solubility on pH and the solubilization of
      naphthalene and anthracene as a function of ionized drug concentration suggest
      that the self-associated dexverapamil is a cationic dimer.

PMID- 7562412
TI  - Molecular profiling and weight determination of heparins and depolymerized
      heparins.
AB  - The recently proposed calibrant LHN-1 (lot F537; henceforth designated F537), for
      the molecular weight (MW) determination by high-performance size-exclusion
      chromatography of heparins, is shown here to have a range too narrow to allow for
      the accurate MW determination of all low molecular weight heparins (LMWHs). We
      have recently demonstrated, by this same methodology, that a chemically degraded
      benzyl ester of unfractionated heparin, heparin mass calibrator (HMC), is a
      better calibrant. Weight-average MW, number-average MW, peak MW, and dispersity
      values were calculated with F537, HMC, and by a reference narrow-range
      calibration method for various LMWHs and unfractionated heparins. Values for
      these parameters determined with HMC were not significantly different from those
      determined by the reference method until the MW of the substance exceeded 15.0
      kDa. In contrast, the MW profile obtained with F537 was appreciably different
      from that obtained by the reference method for samples with MWs > 7.5 kDa. The
      range exhibited by HMC should allow this calibrant to be used for both LMWHs and
      unfractionated heparins.

PMID- 7562413
TI  - Shear stress synergism index and relative thixotropic area.
AB  - Shear stress synergism index and relative thixotropic area are introduced as
      quantifiers of viscous synergism and comparative thixotropy. The utility of these
      terms is demonstrated by their application to microcrystalline cellulose-sodium
      carboxymethyl cellulose (MCC-NaCMC) hydrogel, a starch of different botanical
      origins hydrogels and their combinations.

PMID- 7562414
TI  - A novel skeletal drug delivery system using self-setting calcium phosphate
      cement. 9: Effects of the mixing solution volume on anticancer drug release from
      homogeneous drug-loaded cement.
AB  - The effects of mixing solution volume (0.25-0.65 mL/g) on in vitro drug release
      from a self-setting bioactive calcium phosphate cement containing the anticancer
      agent 6-mercaptopurine (6-MP) as a model compound were investigated. The drug
      release profiles from isolated planar surfaces as well as the entire surfaces of
      cement systems containing 5% 6-MP were measured in simulated body fluid at pH
      7.25 and 37.0 degrees C. The drug release rate from both cement system geometries
      increased with increasing mixing solution volume. Drug release profiles from the
      planar-release and entire-surface-release cement matrix systems were analyzed by
      and found to agree with the Higuchi and Cobby equations, and the kinetic
      parameters were estimated with a nonlinear least-squares computer program. Linear
      relationships were found between the mixing solution volume and the drug release
      rate constants or time required for 50% drug release for both cement release
      geometries. Furthermore, the total pore volume of the cements, as measured by
      mercury porosimetry, increased with increasing mixing solution volume.

PMID- 7562415
TI  - Stereospecific and competitive binding of drugs to human serum albumin: a
      difference circular dichroism approach.
AB  - Simultaneous binding of two drugs to human serum albumin (HSA) was investigated
      by difference circular dichroism (delta CD) spectroscopy. Phenylbutazone and
      diazepam were chosen as specific markers for binding areas I (cumarines) and II
      (indoles), respectively, and their stereospecific interactions with protein were
      selectively characterized. Displacers were drugs known to specifically bind to
      areas I (salicylate) and II (racemic ibuprofen). The results indicate two
      different interaction mechanisms: a direct competition one (diazepam-ibuprofen
      and phenylbutazone-salicylate) and an indirect competition one (diazepam
      salicylate and phenylbutazone-ibuprofen). The two major binding areas on HSA are
      distinct, but not independent, entities. Finally, the dissociation constants of
      marker ligands and competitors complexed to HSA were determined by quantitative
      analysis of CD data.

PMID- 7562416
TI  - A new bioassay for insulin in conscious rabbits by continuous measurement of
      glycemic responses.
AB  - Because of the substantial variability often observed in the determination of
      insulin potency by the United States Pharmacopeia (USP) bioassay method, a large
      number of rabbits are required in order to attain an accuracy of +/- 6% and each
      bioassay needs 2-3 weeks to be completed. In this report, an improved bioassay
      method has been developed. This bioassay was conducted in conscious healthy
      rabbits. The decline in blood glucose levels, following intravenous injection of
      an insulin preparation, was monitored (in uninterrupted manner) by the continuous
      glucose monitoring system developed. A glucose response curve was generated, and
      from this response curve, various pharmacodynamic parameters were easily
      determined. The whole procedure could be completed in 1 day and also achieved an
      accuracy where upon only one rabbit is needed to determine accurately the insulin
      potency. To validate the method, a total of nine healthy rabbits were studied to
      determine the inter- and intra-animal reproducibility. The values of insulin
      potency determined from four pharmacodynamic parameters were compared, and the
      potency calculated from the ABGC (area of the blood glucose response curve under
      baseline) was found to be the most accurate: a mean (+/- SEM) value of 102.3(+/-
      1.2)% was determined by inter-animal study (n = 9) and a value of 100.6(+/- 1.3)%
      by intra-animal study (n = 4). The inter-bioassay variability among the random
      dose bioassays was 1.2% for inter-animal and 1.3% for intra-animal studies. The
      insulin potency in an insulin sample determined by this bioassay had attained an
      overall mean (+/- SEM) value of 101.6(+/- 0.8)% (n = 17).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7562417
TI  - Optimization of in vitro flux through hairless mouse skin of cidofovir, a potent
      nucleotide analog.
AB  - The in vitro flux (4-8 h) of cidofovir (1-[(S)-3-hydroxy-2
      (phosphonomethoxy)propyl]cytosine) was measured across full-thickness hairless
      mouse skin to evaluate potential formulations for local treatment of herpes virus
      infections. The effects of propylene glycol, isopropyl alcohol, oleic acid, pH,
      and cidofovir concentration were examined. In addition, several prototype aqueous
      gel formulations were studied. Flux values (4-8 h) increased linearly with
      cidofovir concentration in both solution and gel formulations. Removal of the
      stratum comeum by tape stripping increased the flux by approximately 400-fold,
      whereas pH (4.5 versus 7) had little effect on flux. The presence of propylene
      glycol, isopropyl alcohol, or their combination did not significantly increase
      mean flux (p > or = 0.05). Pretreatment of the skin with oleic acid resulted in a
      significant enhancement of cidofovir flux (p < or = 0.01). From the measured flux
      values, the calculated concentration of cidofovir achievable in the viable
      epidemis from a 1% cidofovir gel formulation was approximately 14 micrograms/mL,
      which is comparable to the in vitro 50% inhibitory dose (ID50) values for herpes
      simplex viruses HSV-1 and HSV-2.

PMID- 7562418
TI  - Effect of chloride ion on the sedimentation volume and zeta potential of zinc
      insulin suspensions in neutral pH range.
AB  - When zinc insulin suspensions of different pH values were prepared in the
      presence of sodium chloride, an unusually high sedimentation volume was found at
      about pH 6.9. An experimental investigation was conducted in an effort to
      understand this phenomenon. The experiments involved measurements of
      electrophoretic mobilities to calculate zeta potentials and sedimentation volumes
      of zinc insulin suspensions prepared at different NaCl concentrations (0, 17, and
      120 mM) and at various pH values from 5 to 8. The general trend observed was that
      the magnitude of the zeta potential increased with pH when it was higher than the
      isoelectric point of 5.3. When the sodium chloride concentration was 120 mM, a
      very rapid change in zeta potential was observed in the pH range of 6.6 to 7.2,
      with a maximum magnitude of zeta potential at about pH 6.9, the same pH that was
      observed to yield the largest sedimentation volume. Our experimental results
      indicate that the greatest adsorption of chloride ion on the zinc insulin
      suspension particles occurred in the same pH range, which appeared to be
      responsible for the rapid change of zeta potential in that pH range. The
      experimental data were interpreted by DLVO (Derjaguin, Landau, Vervey, and
      Overbeek) theory, which involves a comparison of the forces of electrostatic
      repulsion and of the van der Waals attraction.

PMID- 7562419
TI  - Kinetic evaluation of nonlinear drug elimination by a disposition decomposition
      analysis. Application to the analysis of the nonlinear elimination kinetics of
      erythropoietin in adult humans.
AB  - The disposition-decomposition analysis (DDA) methodology enables isolation of the
      overall elimination and distribution effects in pharmacokinetics and facilitates
      analysis which focuses on drug elimination kinetics and does not require a
      specific structured modeling of drug distribution processes. A computer algorithm
      enables a curve fitting and a kinetic estimation by integration of the
      convolution type integrodifferential equation in the DDA. The approach is
      demonstrated in an analysis of the nonlinear disposition kinetics of
      erythropoietin (Epo) in 10 healthy, adult human subjects who each received 10,
      100, and 500 U/kg i.v. bolus doses of Epo. The nonlinearity is analyzed according
      to a Michaelis-Menten type nonlinear elimination function, considering
      simultaneous fitting to the data from all three doses in each subject. The
      simultaneous fittings produced estimates of the Michaelis-Menten parameters
      (mean, % cv) Vm (901 mU/mL/h, 19.4%) and km (4814 mU/mL, 24.6%). A linear
      clearance parameter is defined as the asymptotic clearance value approached when
      the drug level decreases toward zero. The degree of nonlinearity reached from
      various dosings was quantified in terms of a clearance ratio which is defined as
      the ratio between the linear clearance and the clearance estimated for the
      maximum drug concentration encountered at the given dose level. The subjects
      showed very little nonlinearity at the 10 U/kg dosing with a mean clearance ratio
      of 1.07 (2.1% CV) A statistically significant increase in the degree of
      nonlinearity was observed in the Epo elimination kinetics as the dosing level was
      increased to 100 and 500 U/kg, reaching clearance ratios of 1.66 (14% CV) and
      4.33 (27% CV), respectively. A zero value for the global elimination rate
      parameter in all 30 dosings indicates that Epo's elimination is entirely
      accounted for by nonlinear pathway(s).

PMID- 7562420
TI  - A novel multivariate approach for estimating the degree of similarity in
      bioavailability between two pharmaceutical products.
AB  - Statistical assessment of bioavailability and bioequivalence of drug products is
      generally carried out with a univariate analysis by independently comparing each
      relevant parameter [such as, area under the drug concentration curve (AUC) and
      peak drug concentration (Cmax)] of the test and reference products. The
      assumption is made that AUC and Cmax are independent of each other. In reality,
      AUC, Cmax, and other pharmacokinetic parameters are dependent on each other.
      Therefore, a multivariate approach is theoretically superior. In this report, a
      novel multivariate approach to determine the bioavailability and bioequivalence
      of pharmaceutical products is described. The method determines the bivariate
      confidence ellipse (CE) between Cmax and AUC and the trivariate confidence
      ellipsoid (CED) among Cmax, AUC, and either Tmax or MRT for test and reference
      products. The similarity between the test and reference products can be assessed
      by the fraction of overlapping areas of CE and volumes of CED. The method and its
      comparison with conventional univariate analysis are demonstrated with data
      obtained from a bioequivalence study of ketoconazole tablets.

PMID- 7562422
TI  - Biophysical models as an approach to study passive absorption in drug
      development: 6-fluoroquinolones.
AB  - A preliminary study attempting to assess and explain the intestinal absorption of
      a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented. The
      synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption
      rate constants, and in vitro antibacterial activity data found for these
      homologous compounds are described. A fluorimetric, reverse-phase HPLC method was
      performed for the quantification of the quinolones in absorption and partition
      samples. Equations based on two classic biophysical absorption models are given
      for predicting the intrinsic absorption features of the series according to the
      partition data or merely single structural parameters. In situ absorption rate
      constants were found to increase by a factor of 9.7-13.5 for moderately
      lipophilic derivatives relative to the simplest compound, while antibacterial
      activity decreased only by a factor of 4. In vivo absorption tests with two
      representative members of the series were carried out and the results showed a
      good accordance with those found in situ. This makes these compounds or related
      ones with similar partition features excellent candidates for further
      pharmacokinetic and pharmacological testing. The study can serve as an example of
      how to prevent potential absorption problems associated with the development of
      new drugs.

PMID- 7562421
TI  - Dielectric analysis in the characterization of amorphous pharmaceutical solids.
      1. Molecular mobility in poly(vinylpyrrolidone)-water systems in the glassy
      state.
AB  - The effect of water on the relaxation behavior below the glass transition
      temperature (beta-relaxation) of an amorphous powder, poly(vinylpyrrolidone)
      (PVP, MW 30,000), was studied by subjecting the sample to dielectric analysis in
      the frequency range from 20 Hz to 20 kHz. The material stored at 0% relative
      humidity (RH) (containing 0.05% w/w H2O) exhibited a frequency dependent second
      order beta-relaxation (T beta = -56 degrees C at 500 Hz). The peak frequency
      temperature data could be fitted to the Arrhenius equation, yielding an
      activation energy (Ea) of 36.5 kJ mol-1. Water was found to significantly lower T
      beta, increase the dielectric loss, and increase Ea. The initial decrease in T
      beta was found to be quite significant, as little as 7% w/w H2O lowering T beta
      by 26 degrees C, followed by a more gradual decrease. PVP exposed to 69% RH
      (containing approximately 31% w/w H2O) exhibited T beta at -104 degrees C with an
      activation energy of 46.3 kJ mol-1. The observations that the beta relaxation was
      poorly visible when the water content was 0.05% w/w and that the change in Ea was
      from a low to a high value as the temperature is decreased suggest that thermally
      activated rotational diffusion of water molecules plays a major role in the beta
      relaxation of PVP containing moderate to high water contents. The rate of
      increase in activation energy as a function of H2O/PVP mole ratio exhibited a
      minimum at unity, suggesting that water binding to one site on PVP has a distinct
      effect on the activation energy.

PMID- 7562423
TI  - Isoxazoles. 10. Degradation and enolization kinetics of 4-aminoisoxazolyl-1,2
      naphthoquinone in basic aqueous solution.
AB  - The kinetics of enolization and degradation of N-(5-methyl-4-isoxazolyl)-4-amino
      1,2-naphthoquinone (1) was investigated in aqueous solutions over a pH range of
      7.30 to 12.25, at 35 degrees C and at constant ionic strength (mu = 0.5) using
      reversed-phase HPLC. Pseudo-first-order kinetics was observed throughout the pH
      range studied. The rate of enolization (ke), the keto-enol equilibrium constant
      (Kt), and specific base catalysis rate constant (kCH) were determined. Good
      agreement between the theoretical pH-rate profile and the experimental data
      supports the proposed transformation process. The average recovery for 1 and its
      tautomerization product 2-hydroxy-N-(5-methyl-4-isoxazolyl)-1,4-naphthoquinone 4
      imine (2) from mixtures of different composition was evaluated.

PMID- 7562424
TI  - NMR spectroscopic characterization of adinazolam mesylate: pH-dependent structure
      change in aqueous solution and active methylene.
AB  - The present study is to investigate structural changes of adinazolam mesylate in
      aqueous solution under various pH conditions by NMR spectroscopy. By plotting of
      the signal integration and chemical shifts of the side chain, pKa values for
      imine hydrolysis and the side chain amine were determined. Conformational
      analysis of the side chain was performed with deuterium-induced isotope effects
      on chemical shifts, nuclear Overhauser effects, relaxation times, and energy
      calculations. Hydrogen/deuterium exchange due to an active methylene at the 4
      position under basic conditions was revealed.

PMID- 7562425
TI  - Tissue distribution of LY231617, an antioxidant with neuroprotectant activity, in
      the rat.
AB  - The tissue distribution of a butylated phenol antioxidant, LY231617, which has
      been shown to exert potent neuroprotection action was examined. Preliminary
      pharmacokinetic examination suggests that LY231617 was eliminated in a biphasic
      fashion after iv administration to the rat with a distribution half-life of 5 min
      and an elimination half-life of close to 2.5 h. The volume of distribution of the
      compound was large (7.4 L), consistent with its lipophilic structure. Dosing
      paradigms that have historically resulted in pharmacologically relevant activity
      were examined and were found to generate brain tissue levels of LY231617 of
      approximately 45 micrograms/g.

PMID- 7562426
TI  - Presystemic bradykinin metabolism in sheep and rat nasal homogenates.
AB  - Bradykinin (BK) and its fragments BK(1-8), BK(1-7), and BK(1-5) were incubated
      with sheep nasal homogenates to investigate the extent of peptide metabolism
      within the nasal mucosa. The products for both bradykinin and BK(1-8) degradation
      were found to be BK(1-7) and BK(1-5). BK(1-7) was metabolized to BK(1-5) alone.
      The patterns of degradation suggest that the Pro7-Phe8 bond of bradykinin was
      hydrolyzed first, then BK(1-7) was further hydrolyzed to form BK(1-5). The
      metabolism of bradykinin in rat nasal homogenates and plasma was also
      investigated. BK(1-5) was the only metabolite measurable in the rat nasal
      homogenates, likely due to the activity of an endopeptidase. The reduction in the
      bradykinin degradation rate resulting from the inhibition of angiotensin
      converting enzyme (ACE) or carboxypeptidase N indicates that these enzymes
      participate in mucosal bradykinin metabolism to some degree. In comparison, the
      products of bradykinin hydrolysis in rat plasma were found to be BK(1-8), BK(1
      7), and BK(1-5). These results indicate that the enzyme populations or/and
      activities vary significantly between different species and between different
      tissues within the same species. Although significant aminopeptidase activities
      were detected in the sheep nasal homogenates, bradykinin was not affected by
      their presence, since the N-terminal sequence of bradykinin is not susceptible to
      hydrolysis by most aminopeptidases.

PMID- 7562427
TI  - Quantitative determination of cocaine, cocaethylene (ethylcocaine), and
      metabolites in plasma and urine by high-performance liquid chromatography.
AB  - A sensitive HPLC assay was developed to quantitate the relatively nonpolar
      compounds cocaine, cocaethylene (ethylcocaine), norcocaine, and norcocaethylene,
      as well as the relatively polar metabolites benzoylecgonine and
      benzoylnorecgonine, in rat plasma and urine. The assay in plasma employed two
      successive liquid-liquid extractions and separate injections onto two different
      columns (C8 and C18) to separate and quantitate the relatively polar and nonpolar
      compounds. In urine, the procedure employed a liquid-liquid extraction followed
      by solid-phase extraction (C18 light-load cartridges) and two separate injections
      as for plasma. The UV absorbance of the effluent was monitored at 235 nm. Linear
      standard curves were obtained over the concentration ranges of 25 to 1000 ng/mL
      and 5 to 250 ng/mL in plasma and urine, respectively. The inter- and intraday
      coefficients of variation for the assay of all compounds in plasma and urine were
      < 18% at low concentrations (12.5-100 ng/mL) and < 12% at high concentrations
      (125-250 ng/mL). There was no degradation of these compounds during the
      extraction procedure or during 2 months of storage at -20 degrees C. The
      quantitation limits for the assay of the relatively nonpolar and polar compounds
      in plasma were 25 (2.5 ng in 0.1 mL) and 50 ng/mL (5 ng in 0.1 mL), respectively.
      For the assay in urine, the quantitation limits were 5 (2.5 ng in 0.5 mL) and
      12.5 ng/mL (6.25 ng in 0.5 mL) for the assay of the relatively nonpolar and polar
      compounds, respectively. The methods have been applied to quantitate those
      compounds in rat plasma.

PMID- 7562429
TI  - Dose dependency of the kinetics of dextrans in rats: effects of molecular weight.
AB  - The effects of dose on the serum and tissue kinetics of high and low molecular
      weight (M(r)) dextrans were studied in rats. Single intravenous (iv) doses of 1,
      25, or 100 mg of fluorescein-labeled dextrans with average M(r) of approximately
      4 kD (FD-4) or 150 kD (FD-150) per kilogram of body weight were administered to
      rats, and serum, urine, and various tissues were collected over time. The samples
      were analyzed by a sensitive and specific chromatographic method. For FD-150, the
      area under the serum concentration-time curves (AUCs) increased
      disproportionately when the dose was increased from 1 to 100 mg/kg; the dose
      corrected AUCs were 50.1 +/- 1.9, 85.9 +/- 2.4, and 122 +/- 3 micrograms.h/mL for
      the doses of 1, 25, and 100 mg/kg, respectively (p < 0.05). This increase in the
      dose-corrected AUCs was associated with a high and nonlinear accumulation of FD
      150 in the liver; that is, the percent dose recovered in the liver decreased from
      68.5 +/- 2.4% to 41.5 +/- 3.4% when the dose was increased from 1 to 100 mg/kg (p
      < 0.05). On the other hand, the serum kinetics of FD-4 exhibited dose
      independence [the dose-corrected AUCs were 2.38 +/- 0.04, 2.19 +/- 0.07, and 2.30
      +/- 0.07 microgram.h/mL for the doses of 1, 25, and 100 mg/kg, respectively (p >
      0.05)]. This dose independence was attributed to a high and linear excretion of
      FD-4 into urine as indicated by the percent doses of FD-4 excreted into urine
      [i.e., 82.0 +/- 1.8, 78.7 +/- 4.4, and 82.2 +/- 7.2 for the doses of 1, 25, and
      100 mg/kg, respectively (p > 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562428
TI  - Protein location in liposomes, a drug carrier: a prediction by differential
      scanning calorimetry.
AB  - Location of protein drugs in lipid carriers often determines the stability,
      loading efficiency, and release rate of these drugs from the carriers following
      administration. On the basis of conventional differential scanning calorimetry
      (DSC) measurements, Papahadjopoulos et al. (Biochim. Biphys. Acta 1975, 401, 317
      335) proposed that proteins can be classified into three categories depending on
      their effects on the thermotropic behavior of the lipids, e.g., transition
      temperature and enthalpy. Interactions are usually electrostatic, hydrophobic, or
      their combination. The nature of these interactions are reflected by changes in
      various thermotropic parameters. Our study aims to test the validity of
      Papahadjopoulos' classification. Hydrophilic ribonuclease A, cytochrome c, and
      superoxide dismutase (SOD), as well as hydrophobic cyclosporin A, are used as
      model proteins. Neutral lipids, e.g., dipalmitoylphosphatidylcholine, and/or
      negatively charged lipids, e.g., dipalmitoylphosphatidylglycerol (DPPG), are used
      to prepare liposomes. Results from conventional and high-sensitivity DSC are
      compared. High-sensitivity DSC gives significant, more reproducible results. We
      find that the classification of Papahadjopoulos et al. needs to be modified. No
      hydrophilic proteins bind to liposomes exclusively on the surface by
      electrostatic interactions, and some degree of penetration is observed in most
      cases. An unexpected binding between SOD and DPPG liposomes is observed. The
      binding of SOD to negatively charged lipids may account, at least in part, for
      its ability to protect lipid membranes against oxygen-mediated injury.

PMID- 7562431
TI  - Pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating
      factor in children after intravenous and subcutaneous administration.
AB  - Despite its widespread use, only limited pharmacokinetic data exist for
      recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF),
      especially in children. We evaluated the pharmacokinetics of rhGM-CSF in children
      who had undergone intensive multiagent chemotherapy: 11 children with refractory
      solid tumors received 500-1500 micrograms/m2 of rhGM-CSF (sargramostim) as a
      daily 2-h intravenous (iv) infusion, and seven children received subcutaneous
      (sc) rhGM-CSF at 1500-2000 micrograms/m2/d in two daily injections for 2 weeks.
      Serum samples obtained before and after rhGM-CSF administration were analyzed for
      granulocyte-macrophage colony-stimulating factor (GM-CSF) by a bioassay and by
      ELISA. Concentrations measured by the two methods were highly correlated (r2 =
      0.89, p < 0.001). Following 2-h iv infusions, the concentration-time data were
      best described by a two-compartment, first-order elimination model. The median
      (range) for rhGM-CSF systemic clearance (CI) was 49 mL/min/m2 (range, 15-118
      mL/min/m2), terminal half-life (t1/2) was 1.6 h (range, 0.9-2.5 h), and the time
      the GM-CSF concentration was > 1 ng/mL was 9 h (range, 6-13 h). The CI was not
      dose dependent or related to patient age. The absolute neutrophil count day 14 of
      GM-CSF was significantly related to GM-CSF dosage and platelet count on day 1.
      There was a weak correlation between AUC and duration of neutropenia (p = 0.05).
      The sc concentration-time data were best described by a one-compartment model
      with first-order absorption and elimination. Median apparent clearance was 72
      mL/min/m2 (range, 27-231 mL/min/m2) and t1/2 was 2.3 h (range 0.7-3.8
      h).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562432
TI  - Bradykinin metabolism in rat and sheep nasal secretions.
AB  - The nasal secretions are the first barrier that nasally administered drugs
      encounter. Therefore, the characterization of peptide metabolism in the nasal
      secretions is essential to predict nasal peptide bioavailability. Metabolism of
      bradykinin was measured in rat and sheep nasal secretions to estimate the extent
      of degradation of nasally administered peptide compounds. A single-pass, in situ
      nasal perfusion technique was employed to collect secretions for the
      investigation of peptide metabolism in rat nasal secretions. The protein content,
      mucin concentration, and degree of bradykinin metabolism in perfusate aliquots
      collected over a 2-h period showed that the early perfusate fractions contained
      most of the active secretory materials. Evidence of continuous mucus secretion
      and plasma extravasation was found in the nasal perfusate throughout the entire
      collection period. Sheep nasal secretions were collected with a cotton pledget
      inserted into the nasal cavity. Bradykinin and its fragments were degraded by
      carboxypeptidases and endopeptidases present in both rat and sheep nasal
      secretions. Hydrolysis of Phe5-Ser6 was the major metabolism pathway of
      bradykinin in the rat nasal perfusate, whereas in sheep nasal secretions,
      hydrolysis of the Pro7-Phe8 and Phe8-Arg9 bonds also occurred. Evidence of
      angiotensin converting enzyme, carboxypeptide N, and aminopeptidase activity was
      identified in the rat nasal perfusate with specific substrates and inhibitors.
      The activity of these and other enzymes in the nasal secretions may significantly
      limit the bioavailability of nasally administered peptide drugs prior to their
      exposure to the nasal mucosal tissues.

PMID- 7562430
TI  - A novel approach to preparing water soluble prodrug forms of cisplatin analogues
      bearing chelating diamines.
AB  - A novel method for creating water soluble prodrugs of cisplatin analogues bearing
      chelating diamines is introduced. When 2-(amino-methyl)aniline is reacted with
      K2PtCl4 between a pH of 6 and 7, the neutral chelated complex [2
      (aminomethyl)aniline)dichloroplatinum(II) (1) is isolated. On the other hand,
      when the complexation occurs under acidic conditions (i.e. pH 3), the
      zwitterionic, "open-ring" form [2-(ammonio-methyl)aniline
      N1]trichloroplatinate(II) (2) is obtained, whereby only the aniline nitrogen is
      coordinated to platinum. Compound 2 has a solubility of 10 mM in acidic aqueous
      medium; that is ca. 20 times greater than that of 1. However, 2 rapidly converts
      to compound 1 at physiologic pH; thus 2 functions as a water soluble prodrug of
      1. Both 1 and 2 are equally effective at halting the growth of three different
      human cancer cell lines in vitro, indicating that the prodrug is quantitatively
      converted to the parent drug in a complex, biologically relevant medium. In
      animal experiments, the prodrug form, when given at a dose of 25 mumol/kg three
      times a week for 6 weeks, significantly inhibits the growth of the MXT (M3.2)
      mammary tumor in BDF mice while the same dose of the parent drug has no antitumor
      activity.

PMID- 7562433
TI  - Evaluation of equations for unbound serum concentration prediction of
      carbamazepine and carbamazepine-10,11-epoxide in polytherapy pediatric patients
      with epilepsy.
AB  - We retrospectively evaluated the ability of equations with in vivo population
      binding parameters of our previous study (Method 1) or an average unbound
      fraction of 0.25 of Pynnonen (Method 2) to predict the unbound serum
      carbamazepine (CBZ) concentration in 50 serum samples from 28 polytherapy
      pediatric patients with epilepsy. In 12 serum samples from 10 patients, the
      ability of equations for unbound serum carbamazepine-10,11-epoxide (CBZ-E)
      concentration prediction was also determined in predictive performance with in
      vivo population binding parameters of our previous study (Method A) or an average
      unbound fraction of 0.5 of Pynnonen (Method B). Mean prediction error, mean
      absolute prediction error (MAE), and root mean squared error (RMSE) were
      calculated for each method, and these values served as a measure of prediction
      bias and precision. Method 1 shows a bias to underpredict unbound serum CBZ. The
      MAE and RMSE were lower in Method 2 (MAE = 0.696 microM, RMSE = 0.912 microM)
      than in Method 1 (MAE = 0.946 microM, RMSE = 1.138 microM). Method 2 is superior
      to Method 1 in accuracy and precision. The effects of antiepileptic co
      medications on predictive performance of Method 1 are relatively larger in a co
      medicated group of serum samples with valproic acid (n = 33, MAE = 0.994 microM,
      RMSE = 1.211 microM) than in a group of serum samples without valproic acid co
      medication (n = 17, MAE = 0.853 microM, RMSE = 0.979 microM).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7562434
TI  - Determination of nitrosourea compounds in brain tissue by gas chromatography and
      electron capture detection.
AB  - A relatively simple, high-sensitivity gas chromatographic assay is described for
      nitrosourea compounds, such as BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and
      MeCCNU [1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea], in small
      biopsy samples of brain and other tissues. After extraction with ethyl acetate,
      secondary amines in BCNU and MeCCNU are derivatized with trifluoroacetic
      anhydride. Compounds are separated and quantitated by gas chromatography using a
      capillary column with temperature programming and an electron capture detector.
      Standard curves of BCNU indicate a coefficient of variance of 0.066 +/- 0.018, a
      correlation coefficient of 0.929, and an extraction efficiency from whole brain
      of 68% with a minimum detectable amount of 20 ng in 5-10 mg samples. The assay
      has been facile and sensitive in over 1000 brain biopsy specimens after
      intravenous and intraarterial infusions of BCNU.

PMID- 7562435
TI  - Population characteristics of cyclodextrin complex stabilities in aqueous
      solution.
AB  - Binding constants (K11) of 1:1 complexes of alpha-cyclodextrin, beta
      cyclodextrin, and gamma-cyclodextrin with many substrates (guests) were collected
      from published sources and subjected to statistical analysis. All systems refer
      to 25 +/- 5 degrees C and aqueous solution. The frequency distributions of log
      K11 are satisfactorily described by normal distributions with the following
      parameters (n = number of complexes, mu = population mean, sigma = population
      standard deviation): alpha-cyclodextrin, n = 663, mu = 2.11, sigma = 0.90; beta
      cyclodextrin, n = 721, mu = 2.69, sigma = 0.89; gamma-cyclodextrin, n = 166, mu =
      2.55, sigma = 0.93. Stabilities of pairs of cyclodextrin complexes with a common
      substrate are not precisely correlated, but they do not appear to be wholly
      independent quantities. The stabilities of alpha-cyclodextrin complexes are
      consistent with a recent interpretation of solvent effects on alpha-cyclodextrin
      complex stabilities.

PMID- 7562437
TI  - A mechanistic study of the effects of the 1-alkyl-2-pyrrolidones on bilayer
      permeability of stratum corneum lipid liposomes: a comparison with hairless mouse
      skin studies.
AB  - The influence of a series of 1-alkyl-2-pyrrolidones (C2-C8) on the transport
      behavior of lipophilic and polar/ionic permeants across hairless mouse skin was
      recently investigated by employing a physical model approach that treats the
      stratum corneum barrier as a diffusional system of parallel lipoidal and pore
      pathways. In this previous study, the transport enhancement effects (enhancement
      factor, EHMS) on the lipoidal pathway of the stratum corneum were found to be
      essentially the same for all steroidal probe permeants investigated at various
      concentrations of these 1-alkyl-2-pyrrolidones. In the present research, the
      relationship between solute transport enhancement in the lipoidal pathway of
      hairless mouse skin and the transport enhancement in the stratum corneum lipid
      liposome bilayer was studied by comparing the enhancement factor for the lipoidal
      pathway in the hairless mouse skin, EHMS, with that for the stratum corneum lipid
      liposome, ESCLL, at equal solution concentrations of the 1-alkyl-2-pyrrolidones.
      The release rates of D-mannitol, D-glucose, 3-O-methyl-D-glucose, sucrose, and
      raffinose from stratum corneum lipid liposomes were determined, and the ESCLL
      values for these permeants were compared with the EHMS values obtained with
      hairless mouse skin using the steroidal permeants. An important finding in this
      study was a semiquantitative correlation between the enhancement effects induced
      by the 1-alkyl-2-pyrrolidones, except 1-ethyl-2-pyrrolidone, with the liposome
      bilayer using sugar molecules as permeants and those found with the lipoidal
      pathway in hairless mouse skin using steroid molecules as permeants.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562436
TI  - Studies in phlebitis. VII: In vitro and in vivo evaluation of pH-solubilized
      levemopamil.
AB  - We describe a computational model and an in vitro experiment for assessing
      whether or not a pH-solubilized drug has the potential to precipitate upon
      dilution with blood. The computational model enables an efficient means of
      selecting buffer concentration and pH, and the in vitro test provides a simple
      experimental validation. Both means of screening are applied to the formulation
      of the weakly basic drug levemopamil-HCI. A buffered formulation of levemopamil
      is chosen from the computational model and shown to be free of precipitation upon
      dilution in vitro and to not produce phlebitis in the rabbit ear model. In
      comparison, an unbuffered formulation at the same pH and drug concentration
      precipitates in vitro and causes significant phlebitis in vivo. The results of
      this study reinforce the importance of buffering parenteral formulations instead
      of simply adjusting the pH of the formulation.

PMID- 7562438
TI  - Quantitative structure-pharmacokinetic relationships (QSPR) of beta blockers
      derived using neural networks.
AB  - This study demonstrates the application of neural networks to predict the
      pharmacokinetic properties of beta-adrenoreceptor antagonists in humans. A
      congeneric series of 10 beta-blockers, whose critical pharmacokinetic parameters
      are well established, was selected for the study. An appropriate neural network
      system was constructed and tested for its ability to predict the pharmacokinetic
      parameters from the octanol/water partition coefficient (shake flask method), the
      pKa, or the fraction bound to plasma proteins. Neural networks successfully
      trained and the predicted pharmacokinetic values agreed well with the
      experimental values (average difference = 8%). The neural network-predicted
      values showed better agreement with the experimental values than those predicted
      by multiple regression techniques (average difference = 47%). Because the neural
      networks had a large number of connections, two tests were conducted to determine
      if the networks were memorizing rather than generalizing. The "leave-one-out"
      method verified the generalization of the networks by demonstrating that any of
      the compounds could be deleted from the training set and its value correctly
      predicted by the new network (average error = 19%). The second test involved the
      prediction of pharmacokinetic properties of compounds never seen by the network,
      and reasonable results were obtained for three out of four compounds tested. The
      results indicate neural networks can be a powerful tool in exploration of
      quantitative structure-pharmacokinetic relationships.

PMID- 7562439
TI  - Enhancing the avidity of a human recombinant anti-HIV-1 monoclonal antibody
      through oligomerization.
AB  - The oligomerization by chemical cross-linking of a recombinant human antiviral
      monoclonal antibody (MAb), r447-1, and its characterization are described. This
      MAb binds to an epitope residing in the hypervariable V3 region of the envelope
      protein (gp120/160) of HIV-1. A dimeric form of this MAb displays enhanced
      avidity and was found to be capable of neutralizing a greater variety of lymphoid
      cell culture-adapted HIV-1 variants and HIV-1 primary isolates than its monomeric
      form. The superior binding and breadth of reactivity of this antibody suggests it
      may have utility as a therapeutic and/or prophylactic agent, if it possesses an
      appropriate safety and immunogenicity profile.

PMID- 7562440
TI  - Zidovudine transport in the rabbit brain during intravenous and
      intracerebroventricular infusion.
AB  - The distribution of zidovudine (AZT) between plasma, brain extracellular fluid
      (ECF), and cerebrospinal fluid (CSF) was investigated in a crossover design study
      (n = 5) in unanesthetized rabbits. Drug was administered by intravenous (iv) and
      intracerebroventricular (icv) infusions at the same infusion rate (1.5 mg/h.kg).
      The concentrations of AZT in ECF and CSF were measured by HPLC with microdialysis
      sampling. Plasma concentrations of AZT were quantitated by HPLC. Following iv
      infusion, the ECF- and CSF-to-plasma concentration ratios at steady state (SS),
      were 0.19 +/- 0.05 and 0.29 +/- 0.06, respectively. These values were less than
      unity, indicating the existence of active transport processes for the transport
      of AZT from brain to plasma across the blood-brain barrier (BBB) or blood-CSF
      barrier (BCB). The transport processes were modeled by compartmental model
      analysis, and the results suggest that the transport efficiency of AZT across the
      BBB is asymmetric; that is, the efflux clearance was five times greater than the
      influx clearance. Similarly, the efflux clearance from CSF is three times larger
      than the influx clearance into CSF. The SS concentrations of AZT in brain ECF in
      the same animals that received an icv infusion of AZT in the crossover design
      study were approximately two orders of magnitude greater than those in animals
      following iv infusion at the same dosing rate. Nevertheless, the SS plasma
      concentrations of AZT were similar for both routes of administration (1.2 +/-
      0.19 and 1.2 +/- 0.13 micrograms/mL for iv and icv routes, respectively),
      confirming that the brain is not an organ that exhibits first-pass metabolism
      under the present experimental conditions.

PMID- 7562441
TI  - Stereoselective hydrolysis and penetration of propranolol prodrugs: in vitro
      evaluation using hairless mouse skin.
AB  - Stereoselective hydrolysis of two ester prodrugs of propranolol, isovaleryl
      propranolol (IV-PL) and cyclopropanoyl propranolol (CP-PL), was studied in Tris
      HCl buffer (pH 7.4) containing 0.15 M KCl, skin and liver homogenates, 5% plasma
      in Tris-HCl buffer, skin cytosol and microsomes, and liver cytosol and
      microsomes. The hydrolysis rate constants of (R)-isomers of the prodrugs were 1.1
      30.3 times greater than those of the respective (S)-isomers in tissue
      preparations. Skin showed considerable metabolic activity and very high
      stereoselectivity (R/S ratio: 7.3-30.3). The hydrolyzing capacities of buffer and
      different tissue preparations per milligram of protein content were in the
      following increasing order: buffer < skin homogenate < plasma < liver homogenate.
      The studies with microsomes and cytosol indicated that the esterases, which are
      responsible for the hydrolysis of prodrugs, were mainly present in the cytosolic
      and microsomal fractions of skin and liver, respectively. There was a good
      correlation between the octanol-buffer partition coefficients of propranolol and
      its prodrugs and the skin partition coefficient. In vitro stereoselective
      penetration of propranolol and the prodrugs through full-thickness hairless mouse
      skin was evaluated with flow-through diffusion cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7562442
TI  - Zwitterionic nature of tenoxicam: crystal structures and thermal analyses of a
      polymorph of tenoxicam and a 1:1 tenoxicam:acetonitrile solvate.
AB  - The products of recrystallization of tenoxicam (4-hydroxy-2-methyl-N-2-pyridinyl
      2H-thieno[2,3-e]-1,2-thiazine-3- carboxamide 1,1-dioxide) from ethanol and
      acetonitrile were investigated by thermogravimetric analysis, differential
      scanning calorimetry, and X-ray diffraction. Recrystallization from ethanol
      yielded a polymorph designated 1, and recrystallization from acetonitrile gave a
      solvate 2 with 1:1 stoichiometry. The structures of 1 and 2 were determined by
      single-crystal X-ray methods. Polymorph 1 is triclinic, space group P1, with Z =
      4; solvate 2 is monoclinic, space group P2(1)/n, with Z = 4. In both crystal
      structures, the tenoxicam molecule exists in the zwitterionic form, adopting a
      planar conformation that is stabilized by two intramolecular hydrogen bonds (N(+)
      H...O and N-H...O-). Tenoxicam molecules associate by N(+)-H...O and C-H...N
      hydrogen bonding in both crystal structures. Desolvation of 2 yields a polymorph
      of tenoxicam that is different from polymorph 1. A study of the kinetics of the
      desolvation of 2 by dynamic thermogravimetry yielded estimates of the activation
      energy in the range 69-72 kJ.mol-1. From a comparison of experimental and
      simulated X-ray powder diffraction patterns, neither 1 nor 2 undergoes a
      polymorphic transition upon grinding. X-ray patterns based on the single-crystal
      X-ray data for 1 and 2 are presented as reliable references for their
      identification.

PMID- 7562443
TI  - Construction of a diflunisal ion sensor and its use in automated flow-injection
      methods for assay, content uniformity, and dissolution studies of formulations.
AB  - A diflunisal ion selective electrode of the PVC membrane type with an ion
      exchanger consisting of the tetraheptylammonium-diflunisal ion pair is described.
      The sensor exhibits a rapid, near-Nernstian, selective response to diflunisal
      anion in the pH range 7-10, with a (batch) detection limit of 1 x 10(-5) M. The
      ion sensor was used as a flow detector in an automated flow-injection analyzer to
      develop routine methods for assays (concentration range 1-50 x 10(-4) M, (flow)
      detection limit 2.6 x 10(-5) M), content uniformity, and dissolution studies of
      diflunisal formulations. No serious interference from common ions and tablet
      excipients was found, and the drug can be directly determined in colored samples
      without separation steps. Fourty measurements can be performed automatically per
      hour with a precision of 0.5-1.8% relative standard deviation. The automated
      method for the dissolution test provides a complete dissolution profile by the
      end of the experiment. Using the constructed ion sensor, the intramolecular
      hydrogen bonding of the diflunisal anion was studied, thereby revealing a new
      application of ion sensor potentiometry.

PMID- 7562445
TI  - Molecular topology and quantum chemical descriptors in the study of reversed
      phase liquid chromatography. Hydrogen-bonding behavior of chalcones and
      flavanones.
AB  - The reversed-phase liquid chromatographic hydrophobicity parameters (log K'w and
      S) of several chalcones and flavanones were determined with methanol:water mobile
      phases of different compositions and with trace quantities of n-decylamine and 1
      octanol added to the eluent to minimize the silanophilic interactions present in
      alkylsilane-bonded phases. It has been reported that qualitative hydrogen bonding
      information can be obtained from the relationship between S and log K'w
      determined with these chromatographic conditions. To quantitatively describe the
      hydrogen-bonding discrimination effects observed for the compounds under study,
      the parameter delta was defined as follows: delta(s-log kw) = S-log K'w. With
      topological and molecular orbital calculations, several molecular descriptors
      were computed for test compounds, and multivariate statistical techniques were
      used to examine the informative value of the parameter proposed. The results
      obtained indicate that delta(s-log Kw) encodes structural information mainly
      related to the molecular polarity and the ability of compounds to participate in
      hydrogen-bonding interactions. Similar structural information was also obtained
      for delta(s-log Kw) values of 31 structurally dissimilar compounds.

PMID- 7562444
TI  - Pefloxacine mesilate- and ofloxacin-loaded polyethylcyanoacrylate nanoparticles:
      characterization of the colloidal drug carrier formulation.
AB  - The entrapment of fluoroquinolones, perfloxacine mesilate (PFX) and ofloxacin
      (OFX), in polyalkylcyanoacrylate (PECA) nanoparticles could offer some advantages
      for their biological application; for examples, increasing their bioavailability,
      controlling the drug time-release in blood, and reducing the formation of
      bacterial resistance. To load these two drugs in PECA polymeric bulk, the
      incorporation or adsorption method was performed. These two methods were capable
      of influencing nanoparticle size, molecular weight, release profile, and drug
      polymer association. The incorporation method, particularly for the OFX system,
      achieved PECA nanoparticle suspensions with a mean size value three times higher
      than that obtained in the absence of the drug. In contrast, negligible changes
      were observed for PFX systems. This preparation process also influenced the
      nanoparticle storage stability. The molecular weight values of the various
      nanoparticle preparations were also influenced; that is, the PFX-loaded systems
      showed an enhancement in the average molecular weight values, whereas a reduction
      was observed for OFX-loaded systems. The adsorption method showed no particular
      difference in particle size, molecular weight, and storage stability compared
      with nanoparticles prepared without the drugs. The nanoparticle loading capacity
      was higher for the colloidal systems obtained following the incorporation
      preparation procedure. The release of drug from the nanoparticles was biphasic
      for both preparation processes. The fluoro-quinolone-loaded nanoparticles showed
      an enhancement of the antimicrobial activity against standard bacteria strains
      from 2- to 50-fold compared with the free drugs.

PMID- 7562446
TI  - Legal implications of treating patients with HIV.
AB  - The status of a patient with human immunodeficiency virus (HIV) often has
      significant impact on a physician's willingness and ability to provide quality
      medical care. A physician may face substantial penalties for refusing to treat a
      patient with HIV. Even the referral of a patient with HIV to a specialist in the
      disease may constitute a discriminatory act. The law provides certain guidelines
      which, if followed, may help keep the physician out of the courtroom.

PMID- 7562447
TI  - AIDS and the podiatric medical practice.
AB  - The number of patients with HIV (human immunodeficiency virus) and AIDS (acquired
      immune deficiency syndrome) has increased to the point that every podiatric
      physician in this country will be treating patients who are HIV positive,
      knowingly or not. Podiatric physicians continue to be part of the medical team
      that must bear responsibility for the rapid changes in HIV education. Attention
      must be focused on educating physicians about all aspects of this disease,
      especially the primary and secondary diseases of AIDS and new treatments and
      their side effects. Sterile technique and universal precautions have now taken on
      new importance.

PMID- 7562448
TI  - Guidelines for the prevention of HIV transmission in the podiatric medical
      practice.
AB  - The incidence of human immunodeficiency virus (HIV) infection in the US has
      increased over the past decade. This increase has effected concern regarding the
      risks of HIV infection within the podiatric medical practice. Implementation of
      an effective infection control program for blood-borne pathogens within the
      podiatric medical practice can minimize such risks.

PMID- 7562449
TI  - Nutrition and HIV infection. A continuum of care.
AB  - Nutrition is a fundamental intervention in the early and ongoing treatment of
      human immunodeficiency virus (HIV) disease. Nutrition therapy, in coordination
      with other medical interventions, can extend and improve the quality and quantity
      of life in individuals infected with HIV and living with acquired immune
      deficiency syndrome (AIDS). The author reviews the current literature and
      practice for nutrition use in the treatment of patients with HIV and AIDS.

PMID- 7562450
TI  - Antiseptics and disinfectants. Current issues.
AB  - The authors address current issues regarding use of antiseptics and disinfectants
      with particular emphasis on the problems associated with claims made by
      manufacturers of various chemical agents. Other issues include the efficacy and
      limitations of commercial products, selecting the most appropriate formulation
      for proper disinfection, especially with instruments that come in contact with
      the patient, and preventing or minimizing iatrogenic infections in clinical
      practices. The authors stress that low-level and some intermediate-level
      disinfectants are unreliable because of their narrow safety margin and that
      chemical agents with a high level of activity should be used by all practitioners
      because of multi-drug resistant microorganisms and acquired immune deficiency
      syndrome (AIDS).

PMID- 7562451
TI  - Reading and writing biological literature. Prerequisites to research.

PMID- 7562452
TI  - New method for reconstruction in lateral ankle instability.
AB  - Ankle instability is a frequent sequel following inversion sprain mechanisms of
      injury and has been estimated as occurring in approximately 20% of patients,
      regardless of the type of initial treatment. Mismanagement and undertreatment of
      this common injury contribute to the development of chronic instability symptoms
      with resultant tendencies toward reinjury. Loss of anatomical integrity of the
      injured ligamentous structures, proprioceptive deficits, or superimposed varus
      structural aberrations may all contribute to the chronicity of this condition.
      Surgical reconstruction of the insufficient ligaments can be accomplished through
      a variety of methods to restore stability. The more popular procedures currently
      being performed will be critiqued, and a new variant will be suggested that
      reduplicates the injured collateral ligaments more anatomically and reduces the
      technical complications inherent to operative procedures of this nature.

PMID- 7562453
TI  - Torsion of the tendon of tibialis posterior.
AB  - The authors present a previously undescribed torsion located within the tendon of
      tibialis posterior. The musculotendinous unit of tibialis posterior was isolated
      from 17 lower extremities of cadavers. A small goniometer was constructed and
      used to quantify the degree of torsion located within each tibialis posterior
      tendon. Torsion was present in all 17 cadaver specimens, with a mean of 47.5
      degrees and a range from 21 degrees to 62 degrees. The regional anatomy and
      biomechanical functions of tibialis posterior are discussed, and proposed bases
      for the embryologic origins and functional significance of the torsion are
      presented.

PMID- 7562454
TI  - Variations in foot volume before and after exercise.
AB  - Foot volume measurements were taken on 12 feet of nine female intercollegiate
      volleyball players (mean age of 20 years) before and after a 2-hr rigorous
      practice session. No significant difference was found between foot volume before
      and after exercise. A slight reduction in the foot volume after exercise was
      noted in comparison with the foot volume before exercise. These findings suggest
      that fitting footwear with extra space in front of the longest toe to accommodate
      changes in foot length associated with foot volume increases following exercise
      is not necessary. However, providing extra space in front of the longest toe
      during shoe fitting should still be considered in order to accommodate anterior
      sliding of the foot during athletic activities.

PMID- 7562455
TI  - Clinical perspective of the treatment of fifth metatarsal fractures.
AB  - The authors present a retrospective study of fifth metatarsal fractures. These
      fractures include Jones fractures, avulsion fractures, spiral and oblique
      midshaft fractures, and the author-termed "tulip" fracture (impaction fracture of
      the fifth metatarsal head). These fractures were fixated with the cannulated
      screw, Kirschner wires, and cerclage loop wires combined with Kirschner wires. A
      one-way analysis of variance (ANOVA) was performed on the data to test for any
      significant difference in the fixation type used and the overall healing time.
      The ANOVA was found to be nonsignificant, F(2,10) = 0.379, p < 0.05. Therefore,
      it can be concluded that all three types of fixation work equally well. Other
      analyses were performed on each of the three specific types of fractures to see
      if there was any difference in fixating the fracture versus no fixation and
      immobilization. This information was significant for only the Jones fracture,
      F(1,5)2.23, p < 0.05, meaning that Jones fractures heal in a significantly
      shorter amount of time when some type of open reduction internal fixation is
      used. Since there was no difference in healing time between the different types
      of fixation, the authors advise that the cannulated screw be strongly considered
      because of its efficiency of insertion. In addition, because of the vascularity,
      muscle insertions, and motion related to the fifth metatarsal, the authors
      recommend that most Jones fractures be fixated for a more rapid return to
      function.

PMID- 7562456
TI  - Surgical referrals as evidence of a de facto podiatric medical specialization.
AB  - The authors present evidence on the patterns and correlates of surgical referrals
      to podiatric physicians that suggests a surgical specialty now exists in
      podiatric medicine. The primary factors on which surgical specialization appears
      to be based are residency training, hospital medical staff membership, and
      increased hospital podiatric practice activity. Surgically specialized podiatric
      physicians tend to be younger, but such specialization is not related to either
      the gender or race of podiatric physicians.

PMID- 7562457
TI  - Extensive lipoma of the foot. A case report.

PMID- 7562458
TI  - Magnetic resonance imagery of a calcaneal lipoma.
AB  - An intraosseous lipoma of the calcaneus has been present and stable in this
      patient for at least 16 years; the only change has been an increase in the
      central calcification of the tumor. Because of the apparent stability of the
      lesion and the patient's complete lack of symptoms, no surgical intervention has
      been attempted. A baseline magnetic resonance image of the tumor was obtained to
      confirm the diagnosis and to aid in ruling out malignant degeneration of the
      tumor. The magnetic resonance image appearance of the calcaneal lipoma; increased
      signal intensity on T1-weighted images, with areas of decreased signal intensity
      centrally within the lesion; and corresponding increased signal intensity on the
      T2-weighted images and Short Tau Inversion Recovery suppression, are consistent
      with the descriptions from various texts on magnetic resonance imaging of the
      foot and ankle.

PMID- 7562459
TI  - Cerebral gigantism (Sotos' syndrome). A rare cause of delayed walking and awkward
      gait.
AB  - A case history of an 8-year-old girl with cerebral gigantism (Sotos' syndrome)
      has been presented. Throughout her life, this child has demonstrated all of the
      common features of Sotos' syndrome including large size at birth, excessive
      growth during childhood, dysmorphic craniofacial features, delay in motor and
      speech development, generalized clumsiness, and awkward gait. Family history was
      contributory with delays in early language development and the possibility that
      the child's father had Sotos' syndrome. When evaluating a pediatric patient for
      pes planus, delayed walking, and gait problems, the practitioner should consider
      the entire clinical profile and unusual etiologies.

PMID- 7562460
TI  - Eccrine poroma. A case report.

PMID- 7562461
TI  - Clear cell sarcoma of the foot. A case report.

PMID- 7562462
TI  - Motile Aeromonas as agent of infections of the foot.
AB  - Motile Aeromonas infections of the foot are caused mostly by post-traumatic
      incidence, occurring mostly during summer months. Serious complications such as
      osteomyelitis and amputation can result if the infections go untreated or are
      inadequately treated. The role of each species of motile Aeromonas in
      pathogenesis and response to antimicrobial agents is not well understood because
      of taxonomic uncertainty. As a group, motile Aeromonas respond well to
      aminoglycosides, second-generation and third-generation cephalosporins,
      quinolones, and some beta-lactam antibiotics.

PMID- 7562463
TI  - Congenital absence of the tibial sesamoid.

PMID- 7562465
TI  - Shortening Z-osteotomy.

PMID- 7562464
TI  - Shortening Z-osteotomy.

PMID- 7562466
TI  - Increases in non-N-methyl-D-aspartate glutamatergic transmission, but no change
      in gamma-aminobutyric acidB transmission, in CA1 neurons during withdrawal from
      in vivo chronic ethanol treatment.
AB  - Evoked fast excitatory postsynaptic potentials and slow inhibitory postsynaptic
      potentials were measured in mouse CA1 neurons in hippocampal slices after chronic
      ethanol treatment in vivo. Intracellular recordings were made 2, 4 and 6 hr after
      ethanol withdrawal, i.e., after the beginning of slice preparation. The resting
      membrane potentials were standardized to -60 mV by using constant current
      injection. The fast excitatory postsynaptic potentials were isolated by adding DL
      2-amino-5-phosphonopentanoic acid, bicuculline and nitrendipine to the bathing
      solution and injecting QX-314 into the recording cell; stimulation then evoked a
      monophasic depolarization with a maximum of 16.3 mV at about 30 msec after
      stimulation, which was inhibited by 6-cyano-7-nitroquinozaline-2,3-dione. At 4
      and 6 hr after withdrawal, but not at 2 hr, the estimated fast excitatory
      postsynaptic potential conductance in slices from ethanol-treated mice was
      significantly larger than in those from control animals. There were no changes in
      stimulus/response relation or voltage-dependency of the depolarization. In the
      presence of these blocking agents, the thresholds for elicitation of field
      potentials was decreased at 6 hr from withdrawal. The slow inhibitory
      postsynaptic potentials were isolated by adding DL-2-amino-5-phosphonopentanoic
      acid, 6-cyano-7-nitroquinozaline- 2,3-dione and bicuculline to the bathing
      solution; stimulation of the Schaffer collateral fibers then evoked a monophasic
      hyperpolarization with a maximum of 5.7 mV at about 180 msec after stimulation,
      which was inhibited by the gamma-aminobutyric acidB antagonist saclofen. At the
      three time points, the stimulus/response relation, voltage dependency of the
      hyperpolarization and estimated slow inhibitory postsynaptic conductance in
      ethanol-treated mice did not differ from control animals.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7562467
TI  - Pharmacological characterization of the nonpeptide angiotensin II receptor
      antagonist, U-97018.
AB  - We examined the pharmacological properties of U-97018, a novel nonpeptide
      angiotensin II (AII) receptor antagonist, in various in vitro and in vivo
      studies. U-97018 selectively displaced 125I-AII specific binding in the membrane
      fraction derived from the rat mesenteric artery and adrenal cortex (AT1 subtype)
      with IC50 of 1.3 +/- 0.2 and 7.7 +/- 1.3 nM, respectively, without altering the
      AII binding of the rat adrenal medulla (AT2 subtype). In rat adrenal cortical
      cells, U-97018 inhibited 1 nM AII-induced aldosterone secretion with an IC50 of
      0.48 nM; it shifted concentration-secretion response curve for AII to the right
      and inhibited the maximal response to AII, yielding a pKB of 9.8. Similarly, U
      97018 showed insurmountable antagonism with a pKB of 10.6 against the AII-induced
      contraction in the isolated rabbit aorta. U-97018 had no direct effect on the
      activities of renin and angiotensin converting enzyme in vitro. In pithed rats, U
      97018 inhibited the AII-induced pressor response with an ED50 of 0.28 mg/kg, i.v.
      without any partial agonistic activity. In anesthetized rats and dogs,
      intraduodenal administration of U-97018 at a dose of 1 mg/kg inhibited the AII
      induced pressor response by about 60%. In spontaneously hypertensive rats, U
      97018 at 10 mg/kg p.o. produced antihypertensive effects which lasted for 24 hr
      after administration. Thus, U-97018 is an orally active, insurmountable AII
      receptor antagonist without any agonistic activity.

PMID- 7562468
TI  - The effects of chronic amphetamine treatment on prenatal ethanol-induced changes
      in dopamine receptor function: electrophysiological findings.
AB  - The sensitivity of dopamine (DA) receptors in the mesoaccumbens DA system was
      investigated with extracellular recording and microiontophoresis techniques in
      adult rats that received prenatal ethanol exposure and chronic postnatal
      amphetamine treatment. Pregnant rats were fed with a liquid diet containing 0 or
      35% ethanol-derived calories from gestation day 6 to 20. An ad libitum group
      received laboratory chow and water. Offspring were injected with amphetamine (2
      mg/kg/day s.c.) or saline from postnatal day 22 to 10- to 12-months of age.
      Electrophysiological recording procedures were performed 16 to 24 hr after the
      last amphetamine injection. A supersensitivity of somatodendritic DA
      autoreceptors in the ventral tegmental area was observed in animals exposed
      prenatally to ethanol. This prenatal ethanol exposure-induced supersensitivity
      was not observed after postnatal amphetamine treatment. In control animals,
      postnatal amphetamine treatment did not affect the sensitivity of somatodendritic
      DA autoreceptors. The sensitivity of D-1 DA receptors in the nucleus accumbens
      was reduced by prenatal ethanol exposure. Postnatal amphetamine treatment reduced
      D-1 DA receptor sensitivity in control animals, but not in animals exposed
      prenatally to ethanol. Neither prenatal ethanol treatment nor postnatal
      amphetamine treatment altered the sensitivity of D-2 DA receptors in the nucleus
      accumbens. There were no differences between the ad libitum and 0% ethanol
      derived calorie groups, indicating undernutrition did not affect DA receptor
      function. These results show that prenatal ethanol exposure altered DA receptor
      function in the mesoaccumbens DA system in adult animals. Furthermore, postnatal
      amphetamine treatment was able to eliminate the supersensitivity of
      somatodendritic DA autoreceptors in prenatal ethanol-exposed animals.

PMID- 7562469
TI  - Effect of tolbutamide on the rate of fatigue and recovery in frog sartorius
      muscle.
AB  - The goal of this study was to determine how blocking ATP-sensitive K+ channels
      with tolbutamide affects the excitability and contractility of intact frog
      sartorius muscle during fatigue development. Fatigue was elicited with one
      tetanic contraction every sec for 3 min. During fatigue the resting potential
      decreased by 10 mV although the action potential overshoot remained constant. The
      addition of 2 mmol.liter-1 tolbutamide 60 min before fatigue did not modify the
      effect of fatigue on the resting potential and action potential overshoot. During
      fatigue development the half-repolarization time of control muscles increased by
      0.26 msec in control muscles, although it increased by 0.77 msec in the presence
      of 2 mmol.liter-1 tolbutamide; the difference was significant. The decrease in
      force during fatigue development was not affected by 2 mmol.liter-1 tolbutamide
      (added 60 min before fatigue), whereas the recovery of force after fatigue was
      slower in tolbutamide- exposed muscles than in control muscles. Addition of 2
      mmol.liter-1 tolbutamide after 5 min of recovery reduced the recovery rate of the
      resting potential and half-repolarization time, but did not affect the recovery
      of tetanic force during the first 40 min. Our results are consistent with the
      hypothesis that ATP-sensitive K+ channels are activated during fatigue
      development and that they contribute to the repolarization phase of action
      potentials, but they do not support the hypothesis that ATP-sensitive K+ channels
      contribute to the decrease in force.

PMID- 7562470
TI  - Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO
      dependent mechanism.
AB  - Nebivolol, a beta 1 selective adrenergic receptor antagonist with additional
      properties, is a racemic mixture of (S,R,R,R)- and (R,S,S,S)-enantiomers. We
      investigated its effects on human forearm vasculature. Blood flow was measured
      using venous occlusion plethysmography during brachial artery infusion of drugs.
      Interaction between nebivolol and the L-arginine/nitric oxide pathway was
      investigated via comparison with carbachol (an endothelium-dependent agonist) and
      nitroprusside, and by coinfusion of a competitive inhibitor of nitric oxide
      synthase, NG-monomethyl L-arginine (LNMMA) +/- L-arginine. Nebivolol (354
      micrograms/min) increased blood flow by 91 +/- 18% (mean +/- SEM, n = 8, P < .01)
      whereas an equimolar dose of atenolol had no significant effect. L-NMMA (1
      mg/min) inhibited vasodilation to nebivolol (by 65 +/- 10%) and carbachol (by 49
      +/- 8%) to a significantly greater extent than it reduced responses to
      nitroprusside. Inhibition of nebivolol response by L-NMMA was abolished by L
      arginine (62 +/- 11% inhibition by L-NMMA, 15 +/- 17% inhibition by L-NMMA with L
      arginine, 10 mg/min, n = 8). Vasodilation caused by the (S,R,R,R)- and (R,S,S,S)
      enantiomers was similar. We conclude that nebivolol vasodilates human forearm
      vasculature via the L-arginine/nitric oxide pathway.

PMID- 7562471
TI  - Efflux of intracellular colchicine in lymphocytes with colchicine-specific Fab
      fragments.
AB  - Uptake of [3H]colchicine (2.5 ng/ml) by human lymphocytes in culture was slow in
      the length of time to reach steady state (> 48 hr) and was limited in the maximal
      intracellular colchicine amount (1-2% of total extracellular colchicine). Efflux
      of intracellular colchicine was investigated 40 hr after colchicine cell exposure
      by using either washing of the extracellular medium or adding different
      colchicine-specific Fab fragments:colchicine dose molar ratios of 0.5, 1 and 5.
      Except for the 0.5 dose molar ratio, the kinetics of [3H]colchicine efflux from
      lymphocytes induced by extracellular specific Fab fragments were similar to those
      obtained by washing and were characterized by a first-order decline with half
      lives ranging from 15.5 to 16.4 hr. These half-lives were in the same range as
      those characterizing the dissociation of colchicine from the intracellular
      tubulin receptor. Our data demonstrate that a tightly bound intracellular toxin
      may be extracted by antibody with high affinity for the toxin present in the
      extracellular space at a rate depending on the rate of dissociation of the toxin
      from its receptor.

PMID- 7562472
TI  - Subtype selectivity of the positive allosteric action of alcuronium at cloned M1
      M5 muscarinic acetylcholine receptors.
AB  - The neuromuscular blocking drug alcuronium was found earlier to increase the
      affinity of muscarinic receptors for methyl-N-scopolamine (NMS). This effect
      could be observed in some but not in other tissues. Subtype selectivity of the
      positive allosteric action of alcuronium was now investigated in radioligand
      binding experiments in Chinese hamster ovary (CHO) cells stably transfected with
      the genes encoding the M1-M5 subtypes of muscarinic receptors. Alcuronium had a
      particularly high affinity for the M2 receptor subtype (Kd = 0.6 microM) and its
      affinity for muscarinic receptor subtypes diminished in the order M2 > M4 = M3 >
      M1 > M5. Alcuronium allosterically increased the binding of (3H)NMS to membranes
      containing receptors of the M2 (cooperativity factor alpha = 0.38) and M4
      subtypes (alpha = 0.72) and inhibited the binding of (3H)NMS to membranes
      containing receptors of the M1, M3 and M5 subtypes (alpha = 3.35-4.35). The
      positive effects of alcuronium could also be observed in experiments with (3H)NMS
      binding to intact whole cells, indicating that the positive allosteric action of
      alcuronium occurs by alcuronium binding to receptor domains that are accessible
      from the extracellular space. Alcuronium diminished the affinity for
      (3H)quinuclidinyl benzilate [(3H)QNB] at all five subtypes of muscarinic
      receptors and slowed down the dissociation of both (3H)NMS and (3H)QNB; its
      decelerating effect on radioligand dissociation was most pronounced at the M2
      receptor subtype. Differences between the effects of alcuronium on individual
      muscarinic receptor subtypes are apparently responsible for differences between
      the allosteric effects of alcuronium on muscarinic receptors in various tissues
      that had been described previously.

PMID- 7562473
TI  - Characterization of 125I-endothelin-1 binding to rat and rabbit renal
      microvasculature.
AB  - We characterized 125I-ET-1 binding to renal microvascular membranes isolated from
      the rat, a species showing ETB receptor-mediated renal vasoconstriction, and the
      rabbit in which ET-induced renal vasoconstriction is mediated by the ETA
      receptor. In both species, 125I-ET-1 bound in a manner consistent with a single
      high-affinity site. Scatchard analysis yielded Kd and Bmax values of 20.1 +/- 0.4
      pM and 1343 +/- 64 fmol/mg for the rat and 21.5 +/- 0.9 pM and 810 +/- 64 fmol/mg
      for the rabbit. Competition binding studies with several selective (sarafotoxin
      6c, BQ123) and mixed ETA/ETB (SB 209670) ET receptor ligands showed that the
      renal microvasculature from both species contain ETA and ETB receptors in a
      proportion of 40:60. In the rat, the proportion of ETA receptors was higher in
      the microvasculature than in glomeruli and inner medullary collecting duct cells
      both of which contained > 80% ETB receptors. In the rabbit, the proportion of
      ETA/ETB receptors was similar in the microvasculature and inner medullary
      collecting duct cells (approximately 40:60), whereas glomeruli contained 80% ETB
      receptors. Although ET-induced renal vasoconstriction in the rat and rabbit is
      mediated by different ET receptor subtypes, the proportion of ETA to ETB
      receptors is the same in the renal microvasculature from these species.

PMID- 7562474
TI  - Trifluoperazine modulates [3H]resiniferatoxin binding by human and rat vanilloid
      (capsaicin) receptors and affects 45Ca uptake by adult rat dorsal root ganglion
      neurones.
AB  - Optimum treatment of neuropathic pain includes the use of adjuvant analgesics
      such as antipsychotic drugs and tricyclic antidepressants. Although the mechanism
      of their analgesic action is not known, it is possible that such agents act
      directly on pain pathways. The ability of capsaicin and its analogs to
      selectively deactivate primary afferent neurons provides a basis for their use in
      human therapy to relieve a number of chronic pain conditions. We examined whether
      the phenothiazine antipsychotic drug trifluoperazine (TFP) as well as other
      neuroleptics and tricyclic antidepressants have an effect on the agonist binding
      properties and the activation of the human and rat vanilloid receptors. Binding
      of [3H]resiniferatoxin (RTX) to membrane preparations of human dorsal horn and
      rat whole spinal cord was affected by TFP in a biphasic fashion, with an initial
      25 and 65% enhancement of [3H]RTX binding, respectively, preceding inhibition.
      The apparent Ki values for inhibition were 3.93 +/- 0.13 microM for human dorsal
      horn and 7.91 +/- 0.62 microM for rat spinal cord. Scatchard analyses revealed
      that TFP affected both the affinity and the cooperativity of [3H]RTX binding by
      the receptors, leaving the receptor density unaltered. Similar effects on [3H]RTX
      binding to rat spinal cord membranes were also induced by other antipsychotic
      phenothiazines and other types of antipsychotics, by phenothiazines without
      antipsychotic actions, as well as by tricyclic antidepressants. In cultures of
      dorsal root ganglion neurones, TFP at concentrations that increased [3H]RTX
      binding (1-3 microM) also induced an increase in 45Ca uptake; this increase was
      absent in cultures prepared from capsaicin desensitized animals.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562475
TI  - In vitro formation, disposition and toxicity of N-acetoxy-sulfamethoxazole, a
      potential mediator of sulfamethoxazole toxicity.
AB  - Variation in the formation and disposition of the hydroxylamine of (SMX-HA) is
      thought to play an important role in the pathogenesis of sulfamethoxazole (SMX)
      induced idiosyncratic adverse drug reactions. We hypothesized that, in analogy to
      carcinogenic arylamines, SMX-HA might be further converted to an electrophilic N
      acetoxy metabolite which could play a role in mediating SMX toxicity.
      Accordingly, we chemically synthesized N-acetoxy-SMX, and examined the
      characteristics of its formation, metabolism, cytotoxicity and mutagenicity in
      human and bacterial test systems. The human arylamine N-acetyl-transferases,
      (NAT)1 and NAT2, were capable of converting SMX-HA to N-acetoxy-SMX. NAT1 and
      NAT2 possessed similar affinities for SMX-HA (apparent Km values of 650 and 520
      microM, respectively), but the apparent maximal velocity of the NAT1-mediated
      acetylation was higher than that of NAT2. (1332 vs. 37 nmol/min/U of
      immunoreactive NAT protein). Human peripheral blood mononuclear cells 12,000 x g
      supernatant fractions converted N-acetoxy-SMX mainly back to SMX-HA, and also to
      a lesser extent to SMX, at clinically relevant concentrations. Similar pathways
      were observed in human hepatic cytosolic fractions. In a cytotoxicity assay, N
      acetoxy-SMX was significantly more toxic to human peripheral blood mononuclear
      cells than SMX-HA (16.6 vs. 11.5% dead cells at a concentration of 300 microM). N
      acetoxy-SMX was weakly mutagenic to the Salmonella typhimurium TA100 strain in
      the Ames test. These data suggest that the N-acetoxy metabolites of sulfonamides
      could potentially play a role in mediating sulfonamide idiosyncratic adverse drug
      reactions.

PMID- 7562477
TI  - Anticonvulsant, anxiolytic and discriminative effects of the AMPA antagonist 2,3
      dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX).
AB  - The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic
      seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4
      ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor
      impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At
      30 min after i.p. administration, NBQX was as effective as PCP and diazepam in
      protecting against audiogenic seizures and had a therapeutic ratio slightly
      higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully
      effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30
      min after i.p. administration. The anticonvulsant potential and motor-impairing
      effects of NBQX were evaluated further by the i.p. and the i.v. routes at
      different time points after administration. At all pretreatment intervals, NBQX
      protected against audiogenic seizures more potently than it produced motor
      impairment. NBQX administered i.p. protected against DMCM-induced seizures when
      given 15 min but not 5 min before testing, whereas after i.v. administration NBQX
      produced anticonvulsant and motor-impairing effects in the same dose range. NBQX
      only slightly and non-dose-dependently attenuated the discriminative effects of
      pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced
      no PCP-like or morphine-like discriminative effects in rats, suggesting lack of
      PCP or opiate-like subjective effects. These data demonstrate that NBQX has
      anticonvulsant effects, has limited anxiolytic effects, and does not produce
      subjective effects of PCP or opiate type.

PMID- 7562478
TI  - Disposition of L-carnitine and acetyl-L-carnitine in the isolated perfused rat
      kidney.
AB  - The isolated perfused rat kidney was used to investigate the regulation,
      specificity and concentration-dependence of the renal tubular disposition of L
      carnitine (LC) and its ester, acetyl-L-carnitine (ALC). Tritiated markers were
      used to study the renal disposition of LC and ALC and HPLC was used to purify 3H
      LC and 3H-ALC before radiochemical analysis. At perfusate concentrations
      comparable to those found in plasma in vivo (50 microM for LC and 5 microM for
      ALC), the renal clearance of both analogues was substantially less than GFR (P <
      .05) which, in view of their negligible binding to perfusate proteins, is
      indicative of extensive reabsorption. During the first 20 min of perfusion, the
      percent tubular reabsorption (%TR) of LC and ALC was 94 +/- (SD) 2.6% and 97 +/-
      0.6%, respectively. The extent of 3H-ALC and 3H-LC enrichment of perfusate in
      experiments with 3H-LC and 3H-ALC, respectively, provided evidence for the
      capability of the rat kidney to acetylate LC and deacetylate ALC. In addition, a
      portion of renally generated 3H-ALC and 3H-LC was found to undergo leakage into
      renal tubules and escape subsequent reabsorption. It was also found that the %TR
      of both compounds decreased substantially when the perfusate concentration was
      increased above endogenous levels; each compound was capable of decreasing the
      %TR of the other; and trimethylamine-N-oxide, a metabolite of LC, had no
      significant effect on the renal handling of the carnitine derivatives.

PMID- 7562476
TI  - Effects of the benzodiazepine inverse agonist RO19-4603 on the maintenance of
      tolerance to a single dose of ethanol.
AB  - The time course of the novel benzodiazepine inverse agonist, RO19--4603 (0.075 or
      0.150 mg/kg) in antagonizing the depressant effects of ethanol (EtOH) (0.50, 1.0
      and 1.5 g/kg) and the development of tolerance on locomotor behaviors (e.g.,
      ambulatory count, total distance and stereotypy count) were investigated in
      Sprague-Dawley rats given EtOH injections spaced at 24-hr intervals. A single
      dose of RO19--4603 prevented the development of tolerance to the 0.50- and 1.0
      g/kg EtOH doses 24-hr post-RO19--4603 administration on most locomotor behaviors.
      On Day 1, the 0.150-mg/kg RO19--4603 dose prevented the reduction of motor
      behaviors after the 1.0- and 1.5-g/kg EtOH doses, whereas the 0.075-mg/kg RO19-
      4603 dose prevented the reduction of motor behaviors only after the 1.5-g/kg EtOH
      dose. The 0.075- and 0.150-mg/kg RO19--4603 doses also prevented the EtOH-induced
      reduction of motor behaviors after the 1.5-g/kg EtOH dose 24-hr post-RO19--4603
      administration. RO19--4603 was without effect on activity when given alone. These
      data suggest that the motor impairing effects of EtOH and the development of
      tolerance to them may involve gamma-aminobutyric acidA-benzodiazepine receptor
      mechanisms that when occupied, even briefly by certain benzodiazepine inverse
      agonists, produce long-lasting effects on locomotion and tolerance.

PMID- 7562479
TI  - Selective peptide and nonpeptide ligands differentially bind to angiotensin II
      AT2 receptor and a non-angiotensin II CGP42112 binding site.
AB  - [125I]CGP42112 [Nic-Tyr-(epsilon-CBZ (benzyloxycarbonyl)-Arg)Lys-His-Pro-Ile]
      does not only recognize angiotensin II AT2 receptors, but has also the capacity
      to label a high-affinity, non-angiotensin II binding site, selectively associated
      with macrophages and activated microglia. We have searched for the structural
      requirements of the novel CGP42112 binding site, and compared these with the
      requirements for binding to the angiotensin II AT2 site. We designed a series of
      CGP42112 analogs and evaluated the new compounds by using binding assays on rat
      spleen (CGP42112 site) and rat fetal (angiotensin II AT2 site) membranes. The non
      peptidic analog Z-Arg(Pmc)OH (N alpha CBZ-NG-2,2,5,7,8-pentamethylchroman-6
      sulphonyl-L-Arg), the side chain of CGP42112 substituted on the guanidinium
      group, was selective in recognizing the CGP42112 site, and did not displace
      binding from the angiotensin II AT2 site. This is a potential lead compound for
      development of CGP42112 site-selective analogs. Conversely, the CGP42112 analog
      lacking the CBZ-group (Nic-Tyr-(Ac-Arg)Lys-His-ProOH, III) and the peptide Nic
      Tyr-Lys-His-Ala-HisOH (VI), were selective for the angiotensin II AT2 site, and
      recognized the CGP42112 site poorly. Our results demonstrate that the structural
      requirements for the nonangiotensin II CGP42112 and the angiotensin II AT2
      binding sites are different. We propose that the CBZ group and the free carboxyl
      terminal group, together with their spatial orientation, are key components of
      the molecule for the interaction in the non-angiotensin CGP42112 binding pocket.

PMID- 7562480
TI  - Blood pressure (BP) and renal vasoconstrictor responses to acute blockade of
      nitric oxide: persistence of renal vasoconstriction despite normalization of BP
      with either verapamil or sodium nitroprusside.
AB  - We have previously reported that acute systemic nitric oxide (NO) blockade in the
      conscious rat leads to increases in blood pressure and a profound renal
      vasoconstriction. In the present studies, we investigated the effect on renal
      vascular resistance of normalization of blood pressure (BP) during acute, i.v. NO
      blockade with nitro-L-arginine methyl ester (NAME). We found that two separate
      pharmacologic maneuvers which normalized BP after a transient period of
      hypertension, namely the NO donor sodium nitroprusside (SNP) or the calcium entry
      blocker verapamil (VER), did not reverse the increased renal vascular resistance
      (RVR) produced by acute NAME. In further studies, we prevented the transient
      increase in BP with the same combination of NAME and VER but with simultaneous
      administration of the drugs and in this situation, where the kidney was never
      exposed to a transient rise in renal perfusion pressure, RVR was unchanged
      compared to control. When we used angiotensin II (AII) as an alternative method
      of producing acute increases in BP and RVR, we found that VER reversed both the
      hypertension and the renal vasoconstriction, despite exposure of the kidney to a
      transient increase in BP. These data suggest that acute, transient exposure of
      the kidney to an increased BP during NO inhibition produces a sustained increase
      in RVR that is not reversible with either SNP or VER. The urinary data suggest
      that the combination of NAME and VER have a synergistic effection the renal
      tubule to produce a massive natriuretic and diuretic response.

PMID- 7562481
TI  - Quantitative and qualitative aspects of the hibernation-related reduction of
      morphine physical dependence in the ground squirrel (Citellus lateralis).
AB  - The development of morphine physical dependence in the contrasting brain states
      of the nonhibernating (NH) vs. the hibernating (H) condition was measured in the
      ground squirrel hibernator Citellus lateralis. Morphine was infused continuously
      into the lateral ventricle (3.44, 6.88 and 13.75 micrograms/hr for periods of 1,
      3 and 6 days) in NH and H animals, followed by measurement of the naloxone (1
      mg/kg s.c.) evoked abstinence syndrome during the NH state (i.e., H animals were
      tested after arousal to the NH state). The results showed that morphine treatment
      during the NH state resulted in significant naloxone-evoked abstinence and an
      overall dose- and duration-related increase in the strength of the abstinence
      syndrome. By contrast, morphine treatment during hibernation resulted in
      significantly reduced abstinence compared with that observed after treatment
      during the NH state, with no significant morphine dose-response or duration
      response trends evident. However, H-state morphine treatment did produce a dose
      related reduction of hibernation bout duration. The reduction in the strength of
      dependence during the H state was associated with a qualitative change in the
      abstinence syndrome, as revealed by exploratory factor analysis. This change was
      reflected by an approximate reversal of the rank order of abstinence signs. These
      results demonstrate that hibernation-related changes in central nervous system
      function significantly reduce the liability for and change the character of the
      development of morphine dependence.

PMID- 7562483
TI  - Specificity of p-aminohippurate transport system in the OK kidney epithelial cell
      line.
AB  - Substrate specificity of the p-aminohippurate (PAH) transport system was
      investigated in the OK kidney epithelial cells. PAH uptake by OK cells from the
      basal side was inhibited by beta-lactam antibiotics such as benzylpenicillin
      (PCG) and cefazolin. The inhibition of PAH uptake by PCG was competitive and the
      Ki value was calculated as 108.8 microM. Transcellular transport of PCG across OK
      cell monolayers occurred unidirectionally from the basal to apical side, and
      transcellular transport and basolateral uptake were inhibited by PAH, probenecid
      and beta-lactam antibiotics. The basolateral uptake of cefazolin and cefotiam was
      also inhibited by PAH and probenecid. The basolateral uptake of PAH and PCG were
      not affected by aliphatic dicarboxylates with 3 or 4 carbon atoms, but were
      strongly inhibited by those with 5 or 6 carbon atoms. The inhibitory effect
      became weaker for a longer dicarboxylate with 7 carbon atoms, then increased
      again with increasing number of carbon atoms. Such a pattern of inhibition by
      dicarboxylates is essentially the same with that observed in rat renal proximal
      tubules in situ. These findings suggest that the PAH transport system in OK cells
      has a substrate specificity similar to that in rat renal proximal tubules, which
      is involved in the active secretion of various organic anions including drugs.

PMID- 7562482
TI  - Glucocorticoid receptor activation potentiates the morphine-induced adaptive
      increase in dopamine D-1 receptor efficacy in gamma-aminobutyric acid neurons of
      rat striatum/nucleus accumbens.
AB  - The present study was designed to evaluate the hypothesis that enhanced
      corticosterone levels may facilitate the enduring neuroadaptive effects in the
      brain caused by drugs of abuse. Treatment of primary neuronal cultures of the rat
      striatal complex (striatum/nucleus accumbens, consisting for more than 90% of
      gamma-aminobutyric acid neurons) with 10 microM morphine for 2 hr to 3 days,
      enhanced the maximal stimulatory effect of the dopamine D-1 receptor agonist
      SKF38393 on adenylyl cyclase activity. This adaptive increase in D-1 receptor
      efficacy upon long-term mu-opioid receptor activation was about doubled after
      simultaneous or previous exposure of the neurons to the glucocorticoid receptor
      agonist dexamethasone (EC50 about 2 nM). A similar facilitation of the effect of
      morphine was observed upon exposure of the neurons to relatively high (nanomolar)
      concentrations of corticosterone, whereas the mineralocorticoid receptor agonist
      aldosterone appeared to be ineffective in this respect, indicating the
      involvement of glucocorticoid receptors. Interestingly, whereas morphine exposure
      also enhanced isoprenaline-stimulated adenylyl cyclase activity, this increase of
      beta adrenoceptor efficacy was not at all affected by dexamethasone. In both
      morphine-treated and untreated neurons, low concentrations (< .3 nM) of
      corticosterone or aldosterone, but not dexamethasone, caused a slight (about 20%)
      reduction of dopamine D-1 receptor-stimulated adenylyl cyclase activity,
      indicating the involvement of mineralocorticoid receptors. These data show that
      the morphine-induced adaptive increase of postsynaptic dopamine D-1 receptor
      efficacy (also observed in striatal slices of rats weeks after repeated treatment
      with morphine or cocaine) is strongly enhanced after previous or simultaneous
      glucocorticoid receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562484
TI  - Glutathione and protein thiol homeostasis in brain during reperfusion after
      cerebral ischemia.
AB  - The status of glutathione (GSH) and protein thiol homeostasis was examined in rat
      brain regions during reperfusion after moderate and severe cerebral ischemia. GSH
      levels were decreased in brain regions during reperfusion for 1 hr after moderate
      or severe ischemia for 0.5 hr. Maximal loss of GSH (50-66%) was observed in the
      striatum and hippocampus. The GSH lost from the brain regions was essentially
      recovered as protein-glutathione mixed disulfide (PrSSG) with concomitant loss of
      protein thiols (PrSH). The activities of enzymes such as Na+K+ ATPase, NADH
      dehydrogenase and glutathione reductase were also inhibited but were restored
      after incubation of the brain homogenate with dithiothreitol. The depletion of
      GSH was also accompanied by an increase in the levels of malondialdehyde and
      reactive oxygen species. The total GSH recovered as sum of GSH and PrSSG was
      significantly higher than the sham-operated controls in the hippocampus and
      striatum after 1 hr of reperfusion, after moderate ischemia for 0.5 hr, and at
      the end of 24 hr of reperfusion the GSH-protein thiol homeostasis was restored.
      In contrast after 1 hr of reperfusion after severe ischemia, the GSH recovered as
      sum of GSH and PrSSG was not significantly different from sham-operated controls
      and at the end of 24 hr, 7 of 9 animals died. The recuperation of the brain from
      oxidative stress during reperfusion after moderate ischemia was thus preceded by
      increased recovery of total GSH essentially in the form of PrSSG. Thus, rapid
      restoration of thiol homeostasis in the brain during reperfusion may help the
      brain recover from reperfusion injury.

PMID- 7562485
TI  - Blunting of renal excretory responses to acute volume expansion by nicotine: role
      of renal nerves.
AB  - During smoking, an activated sympathetic nervous system can produce a variety of
      adverse effects on the cardiovascular system. There is evidence of increased
      renal nerve activation during smoking; however, whether the increased renal nerve
      activation in smokers translates into sodium retention by the kidney remains to
      be determined. In the present study, we examined the effect of nicotine on the
      renal nerve-mediated handling of sodium by the kidney during an acute volume
      expansion (VE) with isotonic saline (0.25% of body weight per minute for 30 or 40
      min). Urine flow and sodium excretion from intact and denervated kidneys were
      measured before and during an acute graded VE in anesthetized control and
      nicotine-treated rats (2 micrograms/kg/min for 10 min before and 20 min during
      VE, respectively). In rats treated with nicotine, VE produced a significantly
      blunted diuresis (33% of control by 7.5% VE) and natriuresis (36% of control by
      7.5% VE) from the intact kidneys compared with control rats. Glomerular
      filtration rate was not significantly different between the two groups,
      indicating that hemodynamic changes per se were not responsible for the altered
      volume reflex in rats infused with nicotine. However, renal denervation abolished
      the difference between the control and nicotine-treated rats in diuresis and
      natriuresis in response to VE. In addition, the decrease in renal nerve activity
      (renal sympathoinhibition) in response to acute VE was significantly blunted (53%
      of control by 5% VE) in rats treated with nicotine compared with the control
      rats. Because smoking leads to chronic elevation of nicotine, we simulated a
      chronic elevation of nicotine by administering nicotine (2 mg/kg/day) for 1
      week.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562486
TI  - Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after
      unlimited access to intravenous cocaine.
AB  - To test the hypothesis that cocaine withdrawal is associated with abnormalities
      in serotonin (5-HT) neurotransmission, 5-HT concentrations in the nucleus
      accumbens (NAC) of rats were analyzed with microdialysis both during and after 12
      h of unlimited-access intravenous cocaine self-administration. For comparison
      with previous work, dopamine (DA) levels were also monitored. Self-administration
      produced sustained increases of both 5-HT and DA to approximately 340% of base
      line. During the first 6 h of withdrawal, dialysate 5-HT concentrations decreased
      to 41% of base-line levels obtained before self-administration and to 25% of
      levels in drug-naive control animals. During the same period, dialysate DA
      decreased to 72% of presession base-line concentrations but did not decline below
      control levels. Extracellular 5-HT concentrations were subsequently estimated by
      use of a quantitative microdialysis technique. After 12 h of self-administration
      extracellular 5-HT levels were significantly lower (0.6 +/- 0.3 nM) than levels
      in drug-naive animals (2.0 +/- 0.5 nM) or in rats given only limited-access to
      cocaine (3 h/day; 1.4 +/- 0.2 nM). Additionally, after 12 h of self
      administration low concentrations of intra-accumbens 5-HT applied by reverse
      dialysis significantly elevated DA efflux. This effect was not observed in either
      control animals or in rats given only limited access to cocaine. These results
      suggest that deficient 5-HT neurotransmission may be a significant factor in the
      cocaine withdrawal symptomatology and provide key information regarding
      nondopaminergic mechanisms involved in cocaine dependence.

PMID- 7562487
TI  - Enantioselective effects of experimental diabetes mellitus on the metabolism of
      ibuprofen.
AB  - Diabetes mellitus is associated with numerous metabolic events that may influence
      the elimination of R- and S-ibuprofen and the inversion of R-ibuprofen. Short (3
      days) and long (14 days) term experimental type I diabetes was induced in male
      Sprague-Dawley rats with streptozotocin, and genetically diabetic male Zucker
      rats were used as a model of type II diabetes. Isolated hepatocytes from long
      term streptozotocin-treated rats exhibited significantly greater rate constants
      for ibuprofenyl-coenzyme A (CoA) formation (1.44 +/- 0.05 vs. 0.60 +/- 0.09 hr-1)
      and the elimination of R-ibuprofen (0.34 +/- 0.07 vs. 0.22 +/- 0.07 hr-1)
      relative to control (P < or = .05). These increases were consistent with
      significant induction of hepatic cytochrome P450 (1.14 +/- 0.45 vs. 0.54 +/- 0.10
      nmol/mg protein) and an elevated hepatic free CoA content (313.4 +/- 48.5 vs.
      172.9 +/- 38.6 nmol/g) relative to control (P < or = .05). In hepatocytes from
      type II diabetic rats there were significant reductions (P < or = .05) in the
      rate constants for ibuprofenyl-CoA formation (1.02 +/- 0.12 vs. 1.22 +/- 0.12 hr
      1), R-ibuprofen elimination (0.21 +/- 0.06 vs. 0.34 +/- 0.10 hr-1) and S
      ibuprofen elimination (0.41 +/- 0.07 vs. 0.73 +/- 0.11 hr-1) but no change in
      hepatic content of cytochrome P450 or CoA relative to control. The activity of
      ibuprofenyl-CoA synthetase in whole liver homogenate supplemented with ATP and
      CoA was not influenced by experimental diabetes. In both type I and type II
      diabetes there was a significantly greater exposure of hepatocytes to ibuprofenyl
      CoA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562488
TI  - Cerebrovascular permeability changes during experimental meningitis in the rat.
AB  - Alterations in the blood-brain and blood-cerebrospinal fluid barriers occur
      during bacterial meningitis. Preventing barrier alterations is important as the
      increases in barrier permeability are thought to contribute to adverse
      neurological outcomes. The objective of this study was to characterize
      pharmacokinetically cerebrovascular permeability alterations during meningeal
      inflammation. 14C-Sucrose was used as a quantitative marker of cerebrovascular
      integrity 8 hr after induction of experimental meningitis by intracisternal
      injection of 0, 25 or 200 micrograms lipopolysaccharides. Serum and brain tissues
      were obtained after tracer dosing. 14C-Sucrose influx transfer coefficients
      (Kin(app)) and cerebrovascular volumes (Vbr) were calculated for each brain
      region. Regional Vbr values were unaffected by lipopolysaccharide pretreatment.
      However, statistically significant increases in 14C-sucrose K(in)(app) values
      were observed in various brain regions (1.6- to 3.3-fold from control; P < .05).
      These permeability alterations cannot be attributed to changes in the systemic
      pharmacokinetics of 14C-sucrose as total clearance and the volume of distribution
      were unaffected by lipopolysaccharide treatment. This approach can be used in
      future studies to examine the contribution of various inflammatory mediators to
      altered cerebrovascular permeabilities during experimental meningitis.

PMID- 7562489
TI  - Stimulation by aminooxyacetate of fluorescein uptake in rat renal tubules in
      vitro: role of intracellular alpha-ketoglutarate.
AB  - Uphill base-line uptake of a weak organic anion, fluorescein, in rat renal
      proximal tubules is stimulated by a transaminase inhibitor, aminooxyacetate (AOA,
      1 mM). Considering that an inhibition of cytoplasmic aspartate aminotransferase
      can be accompanied by an elevation in the cytoplasmic alpha-ketoglutarate (KG)
      level, it was hypothesized that the effect of AOA on the fluorescein uptake was
      mediated through an augmentation of the KG gradient across the basolateral
      membrane, which was maintained owing to the Li-inhibitable KG reuptake in the
      cells. In order to test this hypothesis, an influence of Li on the stimulatory
      effects of AOA and KG on the fluorescein uptake was investigated. The hypothesis
      was supported by results showing that LiCl (5 mM) completely abolished the
      stimulatory effect of KG and attenuated almost 3 times that of AOA, whereas Li
      did not affect the base-line fluorescein uptake. Moreover, the stimulatory
      effects of AOA and KG on the uptake were of the same degree but failed to be
      additive, suggesting that they share a common mechanism. Modulatory influences of
      metabolic inhibitors, such as fluoroacetate, malonate, phenylpyruvate and D
      malate, as well as of L-lysine on the effects of AOA and KG also were
      investigated to outline metabolic processes involved in these effects. It is
      concluded that KG metabolism related to its participation in the malate-aspartate
      shuttle, but not to its oxidation in the tricarboxylic acid cycle, is of
      importance for the AOA effect.

PMID- 7562490
TI  - Regulation of glutamate efflux by excitatory amino acid receptors: evidence for
      tonic inhibitory and phasic excitatory regulation.
AB  - Several biochemical and electrophysiological studies have proposed the presence
      of presynaptic receptors that potentiate the release of excitatory amino acids
      (EAA). However, these studies have utilized exogenous EAA agonists and thus have
      assessed the autoregulation of EAA release during conditions of receptor
      hyperstimulation, and not during base line conditions. The aim of the present
      study was to address the question of whether there is a tonic autoregulation of
      base line EAA release. It was demonstrated that in the hippocampus and the
      striatum of freely moving rats, basal outflow of glutamate (Glu) and aspartate
      (Asp) are increased, in a dose-dependent manner, by local application of the
      antagonists of N-methyl-D-aspartate (NMDA) or non-NMDA receptors, suggesting that
      there is an ongoing tonic inhibition of aspartate and Glu outflow by different
      subtypes of EAA receptors. Subsequently, to investigate the effect EAA receptor
      hyperstimulation on Glu outflow, a comprehensive study of the effect of various
      doses of ionotropic and metabotropic EAA agonists on the extracellular levels of
      Glu was performed. At high concentrations, agonists of all known subtypes of EAA
      receptors induced (large) increases in extracellular levels of Glu and in most
      cases caused behavioral stimulation and/or convulsion. This suggests that during
      conditions of high agonist availability, such as the massive Glu release thought
      to occur during pathological conditions, a positive feedback presynaptic
      mechanism may overcome the autoregulatory mechanism operating during base line
      conditions.

PMID- 7562491
TI  - Pharmacological characterization of a new class of nonpeptide neurokinin A
      antagonists that demonstrate species selectivity.
AB  - We examined the pharmacology of ZM253,270 and two representative examples of the
      pyrrolopyrimidines, a new class of nonpeptide, NK-2 receptor (NK-2R) antagonists.
      ZM253,270 competitively inhibited [3H]NKA binding to native or cloned NK-2R from
      hamster urinary bladder (Ki = 2 nM), but was a weaker (48-fold) inhibitor of
      [3H]NKA binding to cloned human NK-2R. A similar species selectivity was observed
      with less potent analogs of ZM253,270. The pyrrolopyrimidines demonstrated only
      marginal inhibition of [3H]SP binding to NK-1R in guinea pig lung membranes (Ki >
      2 microM). In hamster trachea, ZM253,270 competitively antagonized the
      contractile response evoked by neurokinin A (NKA, -logKB = 7.5). In human
      bronchus, ZM253,270 was about 90-fold less potent as a competitive antagonist of
      NKA. The data from ligand binding assays in cloned receptors combined with
      functional receptor assays in airway smooth muscles, demonstrate that the
      nonpeptide antagonist ZM253,270 is selective for the NK2 receptor species that
      are prevalent in hamster, compared with those found in human tissues.

PMID- 7562492
TI  - SB 203220: a novel angiotensin II receptor antagonist and renoprotective agent.
AB  - SB 203220, [(E)-alpha-[[2-butyl-1-[(4-carboxy-1-naphthalenyl)-methyl]-1H-
      imidazol-5-yl]-methylene]-2-thiophene-propanic acid], is a novel nonpeptide
      angiotensin II receptor antagonist with significant oral activity. In the present
      study, we compared the cardiovascular and renal effects of SB 203220 and
      captopril in rats with chronic renal failure induced by 5/6 nephrectomy.
      Preliminary studies indicated that SB 203220 (600 ppm in the diet) and captopril
      (250 mg/l in drinking water) significantly attenuated the pressor activity of
      exogenous angiotensin II and angiotensin I, respectively. After 5/6 nephrectomy,
      significant hypertension was observed such that at 6 weeks, systolic blood
      pressure had reached 176 +/- 9 mm Hg. Both SB 203220 (128 +/- 18 mm Hg) and
      captopril (131 +/- 7 mm Hg) significantly attenuated the hypertension. Urinary
      protein excretion increased progressively after renal ablation (from 7 to 124
      mg/day), and this was attenuated by both SB 203220 (32 +/- 7 mg/day) and
      captopril (42 +/- 6 mg/day). Assessment of serum creatinine and urea nitrogen
      indicated that SB 203220 but not captopril resulted in maintenance of renal
      function, close to that observed in control rats. Both SB 203220 and captopril
      attenuated the renal and left ventricular hypertrophy associated with 5/6
      nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562493
TI  - The pH dependence of cocaine interaction with cardiac sodium channels.
AB  - Previous in vitro and in vivo studies have provided evidence implicating cocaine
      block of cardiac sodium channels as a putative mechanism for cocaine-induced
      arrhythmias and sudden death. Cocaine also has been shown to cause seizures which
      can result in respiratory and/or metabolic acidosis. In this study we
      investigated how changes in both internal pH (pHi) and external pH (pHo) over the
      range of 6.6 to 9.2 modify the sodium channel blocking properties of cocaine in
      isolated guinea pig ventricular myocytes by using the whole-cell variant of the
      patch clamp technique. Use-dependent block produced by a train of 1-sec pulses to
      -20 mV was not affected by changes in pHi, but both the amplitude and time
      constant for approaching steady-state block were significantly affected by
      changes in pHo. Characterization of the time course of cocaine binding during a
      depolarizing pulse indicated that the kinetics of drug interaction with
      inactivated channels were independent of pHi, but were significantly affected by
      changes in pHo. The rate of recovery from channel block at a holding potential of
      -140 mV also was independent of pHi, but strongly dependent on pHo, with the
      unblocking time constant decreasing exponentially as pHo was increased. The
      results of this study indicate that cocaine's effect on cardiac sodium channels
      can be modulated significantly by changes in pHo, and provide further support for
      previously poorly tested assumptions of the modulated receptor hypothesis.

PMID- 7562494
TI  - ATP inhibits the synaptic release of acetylcholine in submucosal neurons.
AB  - Previously, we have shown that adenosine inhibits release of acetylcholine (ACh)
      by acting at A1 presynaptic receptors in guinea pig submucosal synapses. In this
      study, intracellular recordings were made to investigate the actions of ATP and
      some analogs on the synaptic release of ACh. Superfusion of these substances
      decreased the amplitude and duration of electrically induced fast excitatory
      postsynaptic potentials (EP-SPs) in about 90% of the tested neurons. ATP (0.1-30
      microM) effects were concentration dependent with an EC50 of 1.4 microM. ADP, AMP
      and ATP-gamma-S mimicked ATP inhibitory effects and were equally potent and
      efficacious. beta,gamma-Methylene-ATP seemed to act as a partial agonist, causing
      less than 50% of the inhibition obtained with ATP. 2-Methyl-thio-ATP was only
      active at the highest concentration tested whereas alpha,beta-methylene-ATP and
      UTP were inactive (0.3-30 microM). ATP-gamma-S did not alter depolarizations
      induced by exogenous application of ACh, indicating that ATP analogs inhibit
      EPSPs by acting at a presynaptic site. Although the EC50 values were similar for
      ATP and adenosine, the maximum responses (76 +/- 4.5% and 40 +/- 1.6%) were
      different. Adenosine deaminase (which inactivates adenosine) and alpha,beta
      methylene-ADP (an ecto-5'-nucleotidase inhibitor) did not alter ATP-induced
      inhibition of these EPSPs. Inhibition of EPSPs by 30 microM adenosine (maximal
      concentration) and 1 microM ATP (submaximal concentration) were additive. Suramin
      or reactive blue 2 (30 microM), antagonists of ATP actions in several tissues,
      did not modify the effects of ATP on the fast EPSPs. 8-Cyclopentyltheophylline
      inhibited, in a competitive manner, these ATP inhibitory effects. In conclusion,
      ATP inhibits synaptic release of ACh by acting at receptors similar to those
      previously identified as P3-purinoceptors.

PMID- 7562495
TI  - Cardioprotection by a novel recombinant serine protease inhibitor in myocardial
      ischemia and reperfusion injury.
AB  - Polymorphonuclear neutrophils (PMN) play an important role in myocardial
      ischemia/reperfusion (MI/R) injury; however, the role of neutrophilic proteases
      is less understood. The effects of a novel serine protease inhibitor (serpin),
      LEX032, were investigated in a murine model of MI (20 min) and R (24 hr) injury
      in vivo. LEX032 is a recombinant human alpha 1-antichymotrypsin in which six
      amino acid residues were replaced around the active center with those of alpha-1
      protease inhibitor. LEX032 has the ability to inhibit both neutrophil elastase
      and cathepsin G, two major neutral serine proteases in neutrophils, as well as
      superoxide generation. LEX032 (25 or 50 mg/kg) administered i.v. 1 min before
      reperfusion significantly attenuated myocardial necrotic injury evaluated by
      cardiac creatine kinase loss compared to MI/R rats receiving only vehicle (P <
      .001). Moreover, cardiac myeloperoxidase activity, an index of PMN accumulation,
      in the ischemic myocardium was significantly attenuated by LEX032 as compared
      with rats receiving vehicle (P < .001). LEX032 also moderately attenuated
      leukotriene B4-stimulated PMN adherence to rat superior mesenteric artery
      endothelium and markedly diminished superoxide radical release from LTB4
      stimulated PMN in vitro. In a glycogen-induced rat peritonitis model, LEX032 (50
      mg/kg) significantly attenuated PMN transmigration into the peritoneal cavity in
      vivo. In conclusion, the recombinant serine protease inhibitor, LEX032, appears
      to be an effective agent for attenuating MI/R injury by inhibiting neutrophil
      accumulation into the ischemic-reperfused myocardium and by inactivating
      cytotoxic metabolites (proteases and superoxide radical) released from
      neutrophils.

PMID- 7562496
TI  - SB 203347, an inhibitor of 14 kDa phospholipase A2, alters human neutrophil
      arachidonic acid release and metabolism and prolongs survival in murine endotoxin
      shock.
AB  - Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 fatty acyl group
      [predominantly arachidonic acid (AA)] of membrane phospholipids, the products of
      which are further metabolized, forming a variety of eicosanoids and/or platelet
      activating factor. PLA2 activity is significantly enhanced during inflammation
      and therefore offers an intriguing target in designing anti-inflammatory drugs.
      SB 203347 (2-[2-[3,5-bis (trifluoromethyl) sulfonamido]-4-
      trifluoromethylphenoxy] benzoic acid) potently inhibits rh type II 14 kDa PLA2
      (IC50 = 0.5 microM) but exhibits a 40-fold weaker inhibition of 85 kDa PLA2 (IC50
      = 20 microM) using [3H]-AA E. coli as substrate. A specific interaction with rh
      type II 14 kDa PLA2 was confirmed both by observing the pH dependence of its IC50
      and by demonstrating linear inhibition in a "scooting" kinetic model using
      radiolabeled phospholipid reporter substrate in a 1,2-dimyristoyl
      phosphatidylmethanol vesicle. Before evaluating the effect of SB 203347 on AA
      metabolism in intact human neutrophil, we showed that it fully inhibits PLA2
      activity in acid extracted-intact human neutrophil homogenate (IC50 = 4.7
      microM). SB 203347 inhibited A23187-induced intact human neutrophil AA mass
      release in a concentration-dependent manner (IC50 = 1 microM), which coincided
      with reductions in the biosynthesis of platelet-activating factor (IC50 = 1.5
      microM) and leukotriene B4 (IC50 = 2.3 microM). Finally, SB 203347 prolonged
      survival in a mouse model of endotoxin shock delivered i.p. Taken together, the
      data support a role of cellular 14 kDa PLA2 in the formation of AA-derived
      proinflammatory lipid mediator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562497
TI  - Serotonin and norepinephrine uptake inhibiting activity of centrally acting
      analgesics: structural determinants and role in antinociception.
AB  - Although it is well established that the analgesic effects of morphine are
      mediated by opioid receptors, previous studies have shown that some opioids
      additionally inhibit the uptake of serotonin and norepinephrine. The present
      investigation of a diverse group of opioids revealed that structurally
      identifiable subgroups inhibited the neuronal reuptake of these monoamines.
      Phenanthrene opioids with an oxygen bridge between C4 and C5, such as morphine
      and naloxone (group I), did not block norepinephrine or serotonin uptake, whereas
      phenanthrene opioids without the oxygen bridge and the C6-OH moiety, such as
      levorphanol and levomethorphan (group II), did inhibit uptake, as did
      nonphenanthrene opioids, such as d-propoxyphene and methadone (group III).
      Affinity at the mu opioid receptor correlated with antinociceptive potency (r =
      0.87, P < .05). Although the antinociceptive activity of the "active enantiomers"
      of group II and III compounds also correlated with their affinity at the mu
      opioid receptor (r = 0.85, P = .007), additional consideration of serotonin
      uptake inhibiting activity (but not of norepinephrine uptake inhibiting activity)
      significantly improved the correlation between antinociceptive potency and the in
      vitro activity of these compounds (r = 0.915, P = .0017). Additionally, for group
      II and III (but not group I) compounds, smaller differences between enantiomers
      in antinociceptive potency than in mu receptor affinity were noted, presumably
      because of the contribution of uptake inhibition to the antinociceptive activity
      of group II and III compounds. Evidence also is provided suggesting a broader
      role for the combination of mu opioid affinity and 5-hydroxytryptamine uptake
      inhibition in the activity of other antinociceptive agents.

PMID- 7562499
TI  - Intracellular alpha-ketoglutarate controls the efficacy of renal organic anion
      transport.
AB  - Renal organic anion secretion is driven by indirect coupling to the Na+ gradient
      at the basolateral membrane through Na(+)-dicarboxylate cotransport and
      dicarboxylate-organic anion exchange. The impact of changing intracellular alpha
      ketoglutarate (alpha KG) concentrations and gradient on p-aminohippurate (PAH)
      transport was assessed in rat renal cortical slices. Fluorimetric analysis of
      alpha KG indicated that freshly isolated slices averaged 137 +/- 4 nmol/g wet
      weight (approximately 265 microM in cellular water). This value was sustained
      over several hours at 4 degrees C. On incubation at 22 degrees C, intracellular
      alpha KG concentrations rose steadily, reaching levels of 2 (air) to 4 (100% O2)
      times that of fresh tissue. When internal alpha KG was increased by preincubation
      and PAH uptake was determined at a fixed gradient, PAH transport increased with
      increasing internal alpha KG. Conversely, at a fixed internal alpha KG
      concentration, PAH uptake was a linear function of the driving force provided by
      the alpha KG gradient. Thus, intracellular alpha KG is a major determinant of the
      efficacy of renal organic anion transport, and events that alter internal alpha
      KG concentration, gradient, or both are poised to exert significant control over
      organic anion secretion. Kinetic analysis of alpha KG-PAH exchange indicated that
      the Km for alpha KG was 151 microM in basolateral membrane vesicles and 131
      microM in slices. Because PAH transport increased at intracellular alpha KG
      concentrations that should have been saturating, this finding indicates that
      cytoplasmic alpha KG levels must be substantially lower than total tissue
      concentration, i.e., that much intracellular alpha KG must be sequestered.

PMID- 7562498
TI  - Complete reversal by thaliblastine of 490-fold adriamycin resistance in multidrug
      resistant (MDR) human breast cancer cells. Evidence that multiple biochemical
      changes in MDR cells need not correspond to multiple functional determinants for
      drug resistance.
AB  - The emergence of drug resistance is a major obstacle to effective cancer
      chemotherapy. The identification of novel agents that serve as selective, potent
      and nontoxic modulators of drug resistance is thus an important goal for
      improving the success of cancer treatment. Thaliblastine (TBL), a plant alkaloid
      and P-glycoprotein (P-gp) inhibitor, is presently shown to fully reverse 490-fold
      resistance to Adriamycin (AdR) in a multidrug-resistant (MDR) human breast cancer
      cell line (MCF/AdR) that overexpresses P-gp, whereas the same treatment had no
      effect on AdR cytotoxicity in the drug-sensitive parental MCF-7 cells.
      Mechanistic studies showed that this striking resistance reversal was achieved
      without alteration of cellular levels of glutathione and without inhibition of
      glutathione S-transferase, glutathione peroxidase or P450 reductase by TBL, each
      of which is significantly altered in MCF/AdR cells, and each of which has been
      proposed to contribute to AdR resistance in this MDR line. Rather, resistance
      reversal by TBL can be entirely explained by this drug's capacity to restore the
      intracellular accumulation of AdR in the resistant cells. These results establish
      that MDR associated with P-gp overexpression can be fully reversed by the potent
      P-gp inhibitor TBL. They further indicate that although changes in multiple drug
      metabolizing enzymes may accompany the development of MDR, these multiple
      biochemical alterations need not correspond to multiple functional determinants
      for drug resistance.

PMID- 7562500
TI  - Fentanyl-related 4-heteroanilido piperidine OHM3295 augments splenic natural
      killer activity and induces analgesia through opioid receptor pathways.
AB  - Recently, the fentanyl-related compound OHM3295 has been shown to induce a
      naltrexone-sensitive, dose-related analgesia in CD1 mice. However, unlike
      morphine or fentanyl, which are potent immunosuppressive drugs, OHM3295 has been
      found to augment splenic natural killer (NK) activity in a dose-related and
      naltrexone-reversible manner. The present study investigated the type (delta,
      kappa or mu) of opioid receptor involved in analgesia and immunomodulation after
      acute administration of OHM3295. CD1 mice pretreated with beta-funaltrexamine
      (beta-FNA, 40.0 mg/kg) showed an insignificant induction of analgesia (8.4 +/-
      3.7%) after 3.2 mg/kg OHM3295, whereas mice pretreated with vehicle,
      norbinaltorphimine (10.0 mg/kg) or naltrindole (20.0 mg/kg) exhibited 43.6 +/-
      12.6% of maximal analgesia, as determined by the tail-flick latency test.
      Consistent with previous results, acute administration of OHM3295 (3.2 mg/kg)
      augmented splenic NK activity (20.7 +/- 3.4 lytic units [LU]) relative to vehicle
      treated mice (8.2 +/- 0.7 LU). Pretreatment with beta-FNA (40.0 mg/kg) completely
      blocked (9.0 +/- 1.9 LU) OHM3295-mediated augmentation of NK activity, whereas
      pretreatment with norbinaltorphimine (10.0 mg/kg) partially blocked (15.8 +/- 2.2
      LU) the drug-induced effect. However, pretreatment with naltrindole (20.0 mg/kg)
      did not antagonize OHM3295-induced increases in splenic NK activity but rather
      further enhanced (32.3 +/- 4.2 LU) the effect. NK-enriched effector cells from
      OHM3295-treated mice displayed an increase in conjugation with YAC-1 target
      cells, an increase in the percent killing of target cells and a significant
      increase in the number of active killer cells compared with NK-enriched effector
      cells from vehicle-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562501
TI  - Pharmacological characterization of the muscarinic receptor subtype mediating
      contraction of human peripheral airways.
AB  - The postjunctional muscarinic receptors mediating contraction of human bronchial
      smooth muscle have been characterized using four nonselective muscarinic receptor
      agonists and eight subtype selective and nonselective muscarinic antagonists.
      Carbachol, methacholine, oxotremorine M and (+)-cis-dioxolane all caused
      concentration-related contractions of human bronchial smooth muscle with a rank
      order of potency (pD2) of (+)-cis-dioxolane (7.3 +/- 0.2) > oxotremorine M (6.7
      +/- 0.2) > carbachol (6.4 +/- 0.1) > methacholine (5.8 +/- 0.2, n = 5 for all).
      Maximum contractions were not significantly different between agonists, whether
      expressed as absolute my tension changes or as a percentage of the maximum
      response to 0.3 mM histamine. Antagonist apparent affinities (pKB) were
      determined against carbachol-induced contractions and the following rank order
      was obtained; 4-DAMP (9.4 +/- 0.3) > or = atropine (9.1 +/- 0.1) > zamifenacin
      (7.6 +/- 0.1) > hexahydrosiladifenidol (HHSiD; 7.1 +/- 0.1) > or = himbacine (7.0
      +/- 0.3) > or = pirenzepine (6.8 +/- 0.2) > para-fluoro-hexahydrosiladifenidol (p
      F-HHSiD; 6.7 +/- 0.1) > methoctramine (5.3 +/- 0.2). This rank order of
      antagonist affinities is consistent with activation of M3 receptors. The
      affinities of HHSiD, p-F-HHSiD and zamifenacin were, however, lower than those
      reported in guinea pig trachea.

PMID- 7562502
TI  - Targeting 6-thioguanine to the kidney with S-(guanin-6-yl)-L-cysteine.
AB  - Recently, S-(purin-6-yl)-L-cysteine (GC) was shown to be a kidney-selective
      prodrug of 6-mercaptopurine. In the present study, for further development of
      kidney-selective chemotherapeutic agents, GC was synthesized, and its metabolism
      was examined in the rat by cysteine conjugate beta-lyase (beta-lyase) to yield
      the antitumor and immunosuppressant drug, 6-thioguanine (6-TG). The apparent Km
      values obtained with renal mitochondrial and cytosolic beta-lyases were similar,
      but the Vmax value obtained with renal mitochondrial beta-lyase was approximately
      45-fold higher than the Vmax value obtained with renal cytosolic beta-lyase.
      After rats were administered GC (400 mumol/kg), the concentrations of GC in the
      kidney, liver and plasma at 30 min were higher than the corresponding values at
      15 or 60 min. GC concentrations in plasma and kidney were, however, 3- and 5-fold
      higher than that in liver, respectively. Although GC metabolites were not
      detected in plasma, they were detectable in liver and kidney; metabolite
      concentrations at 30 min were higher than those at 15 or 60 min. Renal 6-TG
      concentration at 30 min was nearly 4-fold higher than hepatic 6-TG concentration;
      hepatic and renal 6-thioxanthine and 6-thiouric acid concentrations were similar.
      The amount of GC metabolites excreted in urine within 24 hr was linearly
      proportional to the administered GC dose. Rats administered GC (400 mumol/kg)
      excreted nearly 5-fold the amount of metabolites as rats given an equimolar dose
      of 6-chloroguanine, a GC precursor. These results and the finding that renal 6-TG
      concentrations after GC treatments were in excess of the ED50 of 6-TG (0.5-1.0
      microM) in two human renal carcinoma cell lines (A-498 and CAKI-1) suggest that
      GC may have clinical usefulness as a prodrug of 6-TG.

PMID- 7562503
TI  - The role of serotonin in the effects of opioids in squirrel monkeys responding
      under a titration procedure: I. Kappa opioids.
AB  - The goal of the present study was to determine whether the serotonin (5-HT)
      system is involved in the effects of kappa opioids as measured with the squirrel
      monkey shock titration procedure. With this procedure, electric shock was
      delivered to the monkey's tail and scheduled to increase once every 15 sec from
      0.01 to 2.0 mA in 30 steps. Monkeys responded under a fixed ratio 5 schedule to
      determine the level at which shock intensity was maintained. The intensity below
      which monkeys maintained shock 50% of the time, or the median shock level (MSL),
      and the rate of responding in the presence of shock (RR) were determined after
      the administration of saline and all drug combinations. The kappa opioids U50,488
      and spiradoline increased MSL and decreased RR in a dose-dependent manner. The
      effects of U50,488 and spiradoline on both RR and MSL were enhanced in all three
      monkeys by the 5-HT2 antagonists ketanserin and pirenperone and in one monkey by
      another 5-HT2 antagonist, LY 53857. The effects of U50,488, but not spiradoline,
      were enhanced to a lesser degree by the 5-HT1A receptor agonist 8-OH-DPAT. The
      effects of U50,488 but not altered by the receptor agonist DOI, the 5-HT3
      receptor antagonist MDL 72222 or the alpha-1 adrenergic receptor antagonist
      prazosin. These results suggest that the effects of kappa opioids in the shock
      titration procedure probably involve serotonergic mechanisms that are modulated
      via 5-HT2 and, perhaps, 5-HT1A receptors. Moreover, these interactions probably
      reflect nonspecific decreases in RR rather than alterations in the
      antinociceptive effects of kappa opioids.

PMID- 7562504
TI  - Antinociception and delta-1 opioid receptors in the rat spinal cord: studies with
      intrathecal 7-benzylidenenaltrexone.
AB  - As part of the continuing investigation of the role of spinal delta opioid
      receptors in antinociception, this study characterized the ability of 7
      benzylidenenaltrexone (BNTX), a selective delta-1 opioid receptor antagonist, to
      antagonize the antinociception produced in the rat by intrathecal (i.t.)
      administration of the respective delta-1 and delta-2 opioid receptor agonists,
      DPDPE and [D-Ala2, Glu4]deltorphin (DELT), or the mu receptor agonist DAMGO. In
      the tail flick test, 10-min pretreatment with 1 microgram of BNTX, increased the
      ED50 value of DPDPE from 27.5 micrograms (42.6 nmol) to 114.8 micrograms (177.8
      nmol), but did not increase the ED50 values of either DELT or DAMGO. Increasing
      the dose of BNTX to 3 micrograms did not produce a significantly greater
      antagonism of the antinociceptive effects of DPDPE and did not antagonize the
      antinociceptive effects of DAMGO. However, it did enhance the antinociceptive
      effects of DELT decreasing its ED50 from 5.3 to 0.18 micrograms in the tail flick
      test. In the hot plate test, 10 min pretreatment with 1 microgram of BNTX
      selectively antagonized the antinociceptive effects of DPDPE, but did not
      antagonize the actions of DAMGO or DELT. Increasing the dose of BNTX to 3
      micrograms also did not produce a significantly greater antagonism of the
      antinociceptive effects of DPDPE in the hot plate test, but did antagonize both
      the increase in hot plate latency and the modest decrement in motor function
      produced by 30 micrograms i.t. of DELT. However, the antagonism of these effects
      of DELT occurred much later in time than BNTX's antagonism of the antinociceptive
      effects of DPDPE.

PMID- 7562505
TI  - A primate model of polydrug abuse: cocaine and heroin combinations.
AB  - Abuse of cocaine-opiate combinations ("speedballs") reported clinically was
      simulated in a rhesus monkey model of simultaneous cocaine and heroin self
      administration. The reinforcing effects of nine cocaine-heroin combinations
      (cocaine [0.001, 0.01 and 0.10 mg/kg per injection i.v.] and heroin [0.0001,
      0.001 and 0.01 mg/kg per injection i.v.]) were evaluated for 10 days on a second
      order fixed ratio of 4 (variable ratio of 16:S) schedule and compared with self
      administration of cocaine and heroin alone. Dose-effect curves for cocaine-heroin
      combinations usually were similar to those for cocaine and heroin alone, and
      intermediate doses maintained equivalent high levels of drug self-administration.
      No toxic effects were observed. In drug discrimination studies, cocaine (0.004
      1.3 mg/kg) substitution resulted in a dose-dependent generalization to the
      training dose (0.4 mg/kg i.m.) in all five monkeys. Heroin substitution (0.01-1.0
      mg/kg i.m.) resulted in dose-dependent and complete generalization to cocaine in
      three of five monkeys. Heroin pretreatment (0.1-0.18 mg/kg i.m.) did not change
      the cocaine discrimination dose-effect curve. Pretreatment with an opiate
      antagonist, quadazocine (0.1 mg/kg i.m.), had no effect on the discriminative
      stimulus effects of cocaine but antagonized the cocaine-like discriminative
      stimulus effects of heroin. Pretreatment with a dopamine antagonist, flupenthixol
      (0.018 mg/kg), antagonized the discriminative stimulus effects of cocaine but did
      not affect the cocaine-like effects of heroin. These findings demonstrate the
      feasibility of maintaining self-administration of cocaine-heroin combinations and
      suggest that cocaine and heroin have similar reinforcing and discriminative
      stimulus effects in rhesus monkeys.

PMID- 7562507
TI  - Furosemide renal excretion rate and the effects of the diuretic on different
      tubular sites are modified by endogenous dopamine in normohydrated rats.
AB  - The present study was designed to explore the involvement of endogenous dopamine
      in furosemide excretion and in the actions of the diuretic on tubular sodium
      reabsorption. The dose-response relationship for the diuretic effect of
      furosemide given as i.v. bolus injections (0.2-7.5 mg.kg-1) was studied by
      clearance technique in pentobarbital-anesthetized rats treated with vehicle,
      benserazide (BZ) (25 mg.kg-1 i.v.) or SCH 23390 (50 micrograms.kg-1 + 10
      micrograms.kg-1.min-1 i.v.). Furosemide induced the maximal diuresis 15 to 30 min
      after i.v. administration. The diuretic response was dose-dependent and was
      reduced in the animals treated with BZ and SCH 23390. Fractional sodium excretion
      was also increased by furosemide from 1.8 to 7.5% during the same period. This
      effect was reduced by both BZ or SCH 23390 by 35 to 50%. The effects of
      furosemide on proximal and distal renal tubules were dissected by measuring the
      renal lithium clearance (CLi+). Furosemide effective on proximal tubular sites
      (measured by FENa+ prox = CLi+/Cln) were completely abolished by BZ and SCH
      23390, whereas both drugs reduced furosemide effects on distal tubular sites
      (measured by FENa+ distal = CNa+/CLi+) by 20 to 40%. Furosemide excretion rate
      during the peak response to the diuretic was measured in the urine. BZ and SCH
      23390 diminished furosemide excretion by 45 to 80% as compared with vehicle
      treated animals. The furosemide tubular effects and the proximal and distal
      functions measured by CLi+ determined during the peak response were correlated to
      the maximal excretion rate of furosemide in the urine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7562506
TI  - Effects of CoA-independent transacylase inhibitors on the production of lipid
      inflammatory mediators.
AB  - The enzyme CoA-independent transacylase (CoA-IT) has been proposed to mediate the
      movement of arachidonate between specific phospholipid subclasses, and we have
      shown that two inhibitors of CoA-IT (SK&F 98625 and SK&F 45905) block this
      movement. In this report, we use these inhibitors to further characterize the
      role of CoA-IT in the production of lipid mediators. SK&F 98625 (diethyl 7-(3,4,5
      triphenyl-2-oxo-2,3-dihydro-imidazol-1-yl)heptane- phosphonate) and SK&F 45905
      [2(-)[3-(4-chloro-3-trifluoromethylphenyl)ureido]-4-trifluoromethyl phenoxy]-4,5
      dichlorobenzenesulfonic acid) inhibited CoA-IT activity (IC50 values of 9 microM
      and 6 microM, respectively). Neither compound had any effect on cyclooxygenase,
      14-kDa PLA2 or acetyltransferase activities at concentrations below 20 microM.
      However, SK&F 45905 inhibited 85-kDa PLA2 activity (IC50 = 3 microM), and both
      compounds inhibited 5-lipoxygenase activity (IC50 values of 2-4 microM). In
      ionophore-stimulated neurotrophils, SK&F 98625 and SK&F 45905 blocked the
      liberation of arachidonic acid from phospholipids, which suggests that the
      movement of arachidonate into specific phospholipid pools is a prerequisite for
      release. Both compounds also inhibited the production of platelet-activating
      factor in ionophore-stimulated neutrophils and antigen-stimulated mast cells.
      This inhibition of platelet-activating factor and arachidonic acid release was
      not mimicked by an inhibitor of 5-lipoxygenase, zileuton, which indicates that
      the primary mode of action of SK&F 98625 and SK&F 45905 is via inhibition of CoA
      IT. SK&F 98625 and SK&F 45905 were able to decrease prostaglandin production in
      several inflammatory cells and to block signs of inflammation in ears of phorbol
      ester-challenged mice. Taken together, these results show that blockade of CoA
      IT, which leads to inhibition of arachidonate remodelling between phospholipids,
      results in the attenuation of platelet-activating factor production, arachidonic
      acid release and the formation of eicosanoid products.

PMID- 7562508
TI  - Relative potencies of volatile anesthetics in altering the kinetics of ion
      channels in BC3H1 cells.
AB  - Single channel recording techniques have been used to study effects of the
      volatile anesthetics enflurane, halothane, isoflurane and methoxyflurane, and the
      gaseous agent nitrous oxide, on the properties of nicotinic channels activated by
      acetylcholine. Single channel currents activated by 250 nM acetylcholine were
      recorded from cell-attached patches of BC3H1 mouse tumor cells grown in culture.
      All of the potent volatile agents shortened the duration of individual opening
      events and caused openings to appear grouped together in bursts. The slower time
      constant of channel open-time distributions was decreased 50% by approximately
      0.22% enflurane (0.12 mM), 0.25% isoflurane (0.10 mM), 0.30% halothane (0.16 mM),
      0.076% methoxyflurane (0.21 mM) or 80% nitrous oxide (20 mM) at room temperature.
      Even when values were corrected to 37 degrees C, the concentrations required to
      decrease channel open time are less than clinical dosages. Anesthetic potency in
      altering channel properties was directly related to both clinical potency and
      lipid solubility, although those agents with greater clinical potencies required
      relatively higher concentrations to reduce channel open time. Results are
      interpreted in terms of a simple sequential channel blocking model, a sequential
      blocking model in which anesthetics also enhance the rate at which open channels
      normally close, and a cyclic blocking model in which blocked channels may close
      directly without having to pass back through the open state. All of the agents
      appeared to act in a qualitatively similar fashion and no differences were found
      that could account for the differing clinical profiles of the volatile
      anesthetics.

PMID- 7562509
TI  - Different biliary excretion systems for glucuronide and sulfate of a model
      compound; study using Eisai hyperbilirubinemic rats.
AB  - The disposition of conjugated metabolites (sulfate and glucuronide) was
      investigated in Eisai hyperbilirubinemic rats (EHBR) and normal Sprague-Dawley
      (SD) rats by in vivo and liver perfusion methods. EHBR are mutant rats that have
      conjugated hyperbilirubinemia as an autosomal recessive trait inheritance, and
      they show impaired excretion of organic anions into the bile. 6-Hydroxy-5,7
      dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040), a novel dual
      inhibitor of 5-lipoxygenase and thromboxane A2 synthetase, was used as a model
      compound, because the major metabolites of E3040 are glucuronide and sulfate.
      After the i.v. injection of [14C]E3040 to EHBR and SD rats, the plasma AUC for
      glucuronide was greater in EHBR than in SD rats. The cumulative biliary excretion
      of the glucuronide was impaired to a great extent in EHBR, and the urinary
      excretion was enhanced. There was no significant difference in the cumulative
      biliary and urinary excretion of sulfate between EHBR and SD rats. The influx,
      efflux and sequestration rates of E3040, measured by a multiple indicator
      dilution method in the perfused rat liver, were similar in EHBR and SD rats. The
      biliary excretion of the glucuronide formed in the liver, measured by the liver
      perfusion method, was also severely impaired in EHBR, so the recovery of the
      glucuronide in the outflow specimens was markedly enhanced. The disposition of
      the sulfate did not change in either type of rat.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7562510
TI  - JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive
      enhancer.
AB  - JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)
      1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain
      supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific
      inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a
      strong and durable ex vivo inhibitory effect on PEP in various regions of the rat
      brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine
      vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin,
      and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0,
      4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in
      rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the
      retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before
      acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition,
      coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin
      releasing hormone (at doses at which each drug alone did not prolong the
      retention time) improved the retention time of rats with scopolamine-induced
      amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant
      increase in ACh release in the frontal cortex and hippocampus of young rats at
      oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a
      dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide
      functions inhibiting PEP, that it activates cholinergic transmission and that it
      enhances learning and memory.

PMID- 7562511
TI  - Saralasin suppresses arrhythmias in an isolated guinea pig ventricular free wall
      model of simulated ischemia and reperfusion.
AB  - The effects of saralasin on electrophysiological changes and arrhythmias induced
      by simulated ischemia and reperfusion were examined in an isolated tissue model.
      Segments of guinea pig right ventricles, stimulated regularly, were exposed to
      simulated ischemia for 15 min and then were reperfused with normal Tyrode's
      solution for 30 min. Transmembrane electrical activity and a high-gain
      electrogram were recorded. Arrhythmias and electrophysiological changes
      accompanying simulated ischemia and reperfusion in control preparations were
      compared to those in preparations treated with 0.1 or 1 microM saralasin.
      Simulated ischemia caused abbreviation of action potential duration measured at
      90% repolarization, abbreviation of endocardial effective refractory period (ERP)
      and prolongation of transmural conduction time. Premature ventricular beats,
      ventricular tachycardia and conduction block were observed in approximately 35%
      of control preparations during simulated ischemia. Rapid sustained or
      nonsustained ventricular tachycardia occurred in approximately 60% of control
      preparations in early reperfusion. The overall incidence of arrhythmias and the
      incidence of ventricular tachycardia in early reperfusion were significantly
      decreased by 1 microM but not 0.1 microM saralasin. Saralasin (1 microM)
      prolonged the ERP in normoxic tissues, but it did not alter changes induced by
      ischemia or reperfusion in ERP or the action potential duration at 90%
      repolarization. Prolongation of transmural conduction time during ischemia and
      early reperfusion was significantly inhibited by both concentrations of
      saralasin. However, only 1 microM saralasin reduced the ratio of transmural
      conduction time to ERP enough to prevent arrhythmias. Our observations
      demonstrate that saralasin exerts antiarrhythmic effects in myocardial
      reperfusion by a mechanism independent of circulatory and central actions.

PMID- 7562512
TI  - Time-dependent antinociceptive interactions between opioids and nucleoside
      transport inhibitors.
AB  - Endogenous purinergic systems are important in spinal mechanisms of
      antinociception. Antinociception induced by spinal mu opioid receptor-selective
      agonists, in particular, appears to be mediated in part by opioid-stimulated
      adenosine release. Nucleoside transport system(s) have been implicated both in
      adenosine release and in its reuptake at spinal sites. The present investigations
      were designed to determine the significance of nucleoside transport system(s)
      inhibition in vivo in antinociception induced by opioids administered
      intrathecally in mice. Dilazep, but not dipyridamole or s (4-nitrobenzyl)-6
      thioinosine, nucleoside transport system(s) inhibitors, induced time- and dose
      dependent antinociception in the tail-flick test, putatively via spinal adenosine
      reuptake inhibition. Each nucleoside transport system(s) inhibitor, at doses that
      have no significant effects alone, enhanced adenosine-mediated antinociception
      when coadministered intrathecally. Concurrent treatment of mice with opioid
      receptor-selective agonists and nucleoside transport system(s) inhibitors had
      varying effects on antinociception, depending on the timing of the nucleoside
      transport inhibitor. In general, antinociception induced by mu opioid receptor
      selective agonists was inhibited by pretreatment, was not affected after
      coadministration and was enhanced by post-treatment, with nucleoside transport
      system(s) inhibitors. In contrast, antinociception induced by delta opioid
      receptor-selective agonists was enhanced by nucleoside transport system(s)
      inhibitors in all treatment protocols. These results provide in vivo evidence
      that alterations in adenosine movements into or out of spinal neurons via the
      nucleoside transport systems can induce antinociception and enhance or inhibit
      opioid-mediated antinociception. These data also support the hypothesis that
      adenosine plays significant but independent roles in antinociception induced by
      mu and delta opioid receptor-selective agonists.

PMID- 7562513
TI  - The pharmacology of SCH 50911: a novel, orally-active GABA-beta receptor
      antagonist.
AB  - Experiments were conducted to characterize the pharmacology of SCH 50911 ((+)-5,5
      dimethyl-2-morpholineacetic acid hydrochloride), a structurally novel GABA-B
      receptor antagonist. Although more potent GABA-B antagonists have been reported,
      in this study SCH 50911 was compared with CGP 35348, a moderately potent and
      selective GABA-B antagonist with acceptable in vivo activity. SCH 50911 was more
      potent to inhibit the binding of GABA to the GABA-B receptor in rat brain (IC50 =
      1.1 microM) than CGP 35348 (IC50 = 62 microM). SCH 50911 had no binding affinity
      for GABA-A, histamine H1, histamine H3, dopamine D1, dopamine D2, serotonin 5
      HT2, or muscarinic m1, m2, or m4 receptors. However, SCH 50911 (IC50 = 2.2
      microM) was active in a nonspecific muscarinic receptor binding assay, but was
      devoid of muscarinic agonist or antagonist activity in the isolated guinea pig
      ileum. SCH 50911 blocked inhibitory responses to baclofen of the guinea pig
      trachea in a competitive manner (pA2 = 5.8 +/- 0.004). CGP 35348 was 19-fold less
      potent in this assay (pA2 = 4.6 +/- 0.15). In vivo, SCH 50911 (ED50 = 2.9 mg kg
      1, s.c.) and CGP 35348 (ED50 = 5.8 mg kg-1, s.c.) blocked the antitussive effects
      of baclofen in the guinea pig. In the cat, both SCH 50911 (10 mg kg-1, i.v.) and
      CGP 35348 (10 mg kg-1, i.v.) shifted the antitussive dose response relationship
      for baclofen to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562514
TI  - Characterization of the antiabsence effects of SCH 50911, a GABA-B receptor
      antagonist, in the lethargic mouse, gamma-hydroxybutyrate, and pentylenetetrazole
      models.
AB  - Recent studies have shown that gamma-aminobutyric acidB (GABAB) receptor
      antagonists suppress absence seizures in animal models. (+)-5,5-Dimethyl-2
      morpholineacetic acid, hydrochloride (SCH 50911) is a new GABAB antagonist that
      is structurally dissimilar to previously studied GABAB antagonists such as 3
      aminopropyl-diethoxymethyl-phosphinic acid (CGP 35348), 3-aminopropyl-n-butyl
      phosphinic acid (CGP 36742) or 3-aminopropyl-cyclohexylmethyl-phosphinic acid
      (CGP 46381). In this study we measured the antiabsence effects of SCH 50911 in
      three animal models: the lethargic (lh/lh) mutant mouse, which has spontaneous
      absence seizures; and two rat models in which absence seizures were induced by
      administration of either gamma-hydroxybutyrate or pentylenetetrazole. SCH 50911
      abolished seizures in all three models in a dose-dependent fashion (ID100 = 8-170
      mumol/kg). In each model SCH 50911 was more potent (ID50 = 2-22 mumol/kg) than
      the following antiabsence compounds: the GABAB antagonist CGP 35348 (ID50 = 210
      890 mumol/kg); ethosuximide (ID50 < or = 142-1240 mumol/kg); trimethadione (ID50
      = 520-1100 mumol/kg); and valproic acid (ID50 = 900-2360 mumol/kg). SCH 50911 was
      equipotent with the GABAB antagonist CGP 46381 (ID50 = 20 mumol/kg) in the lh/lh
      mouse model. These findings suggest that antiabsence activity may be a defining
      feature of GABAB receptor antagonists and provide a rationale for pursuing
      clinical trials of GABAB receptor antagonists in human patients with absence
      seizures.

PMID- 7562515
TI  - The pharmacological profile of iloperidone, a novel atypical antipsychotic agent.
AB  - Iloperidone (1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]
      3-methoxyphenyl]ethanone) demonstrated a potent antipsychotic profile in several
      in vitro and in vivo animal models. Iloperidone displaced ligand binding at D2
      dopamine receptors (IC50 = 0.11 microM) and displayed a high affinity for
      serotonin (5-HT2) receptors (IC50 = 0.011 microM) and alpha-1 receptors (IC50 =
      0.00037 microM). In vivo, iloperidone antagonized apomorphine-induced climbing
      behavior in mice at low doses with good oral bioavailability, prevented 5-HT
      induced head twitch in rats at low doses, and inhibited self-stimulation behavior
      in rats, pole climb avoidance in rats and continuous Sidman avoidance responding
      in monkeys. The latter assay also demonstrated a good duration of action.
      Iloperidone was substantially less active in models of extrapyramidal side effect
      (EPS) liability, such as preventing apomorphine-induced stereotypy and causing
      catalepsy in rats. In single dopamine neuron sampling studies, iloperidone
      demonstrated clozapine-like effects on the number of active midbrain dopamine
      neurons. Based on the significant increase in the open arm time seen after
      iloperidone treatment in the elevated plus maze assay and increased interaction
      score in social interaction, iloperidone may also have favorable effects in the
      clinic on anxiety and, possibly, negative symptoms. Clinical trials are under way
      of the use of iloperidone for the treatment of schizophrenia.

PMID- 7562516
TI  - Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5
      HT2C receptors.
AB  - The present study assessed compounds displaying affinity for 5-HT1A, 5-HT1B, 5
      HT2A and 5-HT2C receptors for their ability to substitute for, enhance or
      antagonize the discriminative stimulus effects of cocaine (10 mg/kg) in rats. In
      substitution tests, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT; 0.2-1.6 mg/kg), the 5-HT1A/B receptor agonists RU 24969
      (0.25-2 mg/kg) and CGS 12066B (2-16 mg/kg), the 5-HT1B/2C receptor agonists m
      chlorophenylpiperazine (mCPP; 0.25-2 mg/kg) and m-trifluoromethylphenylpiperazine
      (TFMPP; 0.125-2 mg/kg), the 5-HT2A/2C receptor agonist 1-(4-bromo-2,5
      dimethoxyphenyl)-2-aminopropane ([+/-]-DOB; 0.0625-0.5 mg/kg), the 5-HT2C
      receptor agonist MK 212 (0.25-1 mg/kg) and the nonselective 5-HT receptor agonist
      quipazine (1-8 mg/kg) engendered 30% to 70% cocaine-appropriate responding. The
      DA receptor antagonists SCH 23390 (0.025 or 0.05 mg/kg) and haloperidol (0.125 or
      0.25 mg/kg) failed to block the partial substitution of RU 24969 (1 mg/kg) for
      cocaine. In combination tests, a fixed dose of either quipazine (4 mg/kg), RU
      24969 (0.25, 0.5 or 1 mg/kg) or TFMPP (0.5 mg/kg) but not 8-OH-DPAT (0.4 mg/kg)
      or CGS 12066B (16 mg/kg) produced a leftward shift in the cocaine dose-response
      curve (0.625-5 mg/kg). In contrast, coadministration of either mCPP (0.25-2
      mg/kg) or MK 212 (0.125-2 mg/kg) plus a dose of cocaine (5 mg/kg) that produced >
      85% cocaine-appropriate responding when given alone partially antagonized
      cocaine; mCPP (1 mg/kg) also produced a rightward shift in the cocaine dose
      response curve. Neither 8-OH-DPAT (0.2-1.6 mg/kg), (+/-)-DOB (0.125-0.5 mg/kg)
      nor quipazine (2-8 mg/kg) blocked the cocaine stimulus. The 5-HT1A receptor
      antagonist NAN 190 (0.2-0.8 mg/kg), the 5-HT2A/2C receptor antagonist LY 53857
      (0.5-4 mg/kg) and the 5-HT/DA receptor antagonist pirenperone (0.5-4 mg/kg)
      neither substituted for nor enhanced cocaine; however, pirenperone but not NAN
      190 or LY 53857 partially blocked the cocaine (10 mg/kg) response. Although 5-HT
      receptor compounds do not substitute for cocaine, several 5-HT receptor agonists
      (i.e., the indole derivative RU 24969 and the arylpiperazines mCPP, MK 212, TFMPP
      and quipazine), but not antagonists, differentially modulate the stimulus effects
      of cocaine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562518
TI  - Effects of route of administration on dextromethorphan pharmacokinetics and
      behavioral response in the rat.
AB  - One of the potential problems of using dextromethorphan as a neuroprotective or
      anticonvulsant agent is the phencyclidine-like behavioral effects that have been
      attributed to its major metabolite dextrorphan. Because previous behavioral
      studies of dextromethorphan have generally failed to consider metabolic
      conversion to this metabolite, the present studies were conducted to examine the
      effects of route of administration on dextromethorphan pharmacokinetics and
      locomotor activity in the rat. The bioavailability of dextromethorphan was 1.3
      fold lower and the formation of dextrorphan and other metabolites was 3-fold
      greater after i.p. injection of 30 mg/kg of dextromethorphan as compared to the
      s.c. route, indicating substantial effect of first-pass metabolism. Plasma
      dextromethorphan was correlated with brain dextromethorphan (r = 0.84, P < .001),
      and the brain/plasma concentration ratio was about 6.5. Plasma-free dextrorphan,
      but not conjugated dextrorphan, was correlated with brain dextrorphan (r = 0.97,
      P < .001). Tmax of brain dextrorphan was earlier, and Cmax was higher after i.p.
      injection of dextromethorphan than s.c. administration (60 min vs. 120 min and
      1.0 nmol/g vs. 0.2 nmol/g). Dextromethorphan (60 mg/kg i.p.) increased locomotor
      activity in the rat 60 min postdose, whereas the same dose of dextromethorphan
      administered by s.c. injection was without effect. These data demonstrate the
      route-specific effects on the disposition of dextromethorphan and dextrorphan in
      rat plasma and brain, as well as the behavioral consequence of the difference.

PMID- 7562517
TI  - Pharmacological characterization of purinoceptor-mediated constriction of
      submucosal arterioles in guinea pig ileum.
AB  - Sympathetic nerve stimulation causes a constriction of submucosal arterioles that
      is mediated by ATP acting at P2 receptors. In the present study, we examined the
      P2 receptor subtype mediating this response. A computer-assisted video monitoring
      system measured drug-induced changes in arteriolar diameter (resting diameter
      approximately 40-80 microns) in pieces of submucosa in vitro. The rank-order
      potency for vasoconstriction caused by several ATP analogs was alpha,beta
      methylene ATP (alpha,beta-MeATP) > beta,gamma-methylene ATP = 2-methylthioATP >
      ATP > ADP. Constrictions caused by alpha,beta-MeATP were competitively
      antagonized by suramin (KB = 3.2 microM) and were noncompetitively blocked by
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (KB = 0.5 microM).
      Norepinephrine-induced constrictions were not affected by suramin (100 microM) or
      by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (3 microM). Extracellular
      solutions with 0 added calcium prevented constrictions caused by alpha,beta-MeATP
      (0.1-1.0 microM), but not those caused by norepinephrine (3 and 10 microM).
      Nifedipine (0.3 and 1 microM) reduced constrictions caused by 40 and 60 mM
      extracellular potassium chloride, but not those caused by alpha,beta MeATP. These
      data indicate that P2X receptors mediate constriction of submucosal arterioles.
      P2X-mediated vasoconstriction is dependent on extracellular calcium, but calcium
      entry through nifedipine-sensitive calcium channels does not contribute to P2X
      mediated vasoconstriction.

PMID- 7562519
TI  - Cyclosporin A affects red blood cell deformability in vivo but not in vitro in
      guinea pig.
AB  - A hemorheological mechanism has been proposed for the hemodynamic effects of
      cyclosporin A (CsA). In vivo and in vitro effects of CsA on red blood cell (RBC)
      deformability were investigated in guinea pigs. RBC transit time, measured by a
      cell transit analyzer, was found to be prolonged, implying impaired deformability
      in guinea pigs treated with CsA (10 mg/kg/day) for 7 days. Blood CsA
      concentration was approximately 900 ng/ml. RBC cytosolic calcium concentration
      was higher in the CsA-treated groups than in the control group. RBC lipid
      peroxidation was not affected. Combining pentoxifylline injections (100
      mg/kg/day) with CsA therapy did not prevent the effect on RBC deformability and
      cytosolic calcium concentration. CsA did not affect RBC transit time and
      cytosolic calcium concentration in vitro. Thus, the influence of CsA on RBC
      deformability appears to be an indirect effect that is mediated by the
      alterations in RBC calcium homeostasis.

PMID- 7562520
TI  - Systemic administration of rhIGF-I enhanced regeneration after sciatic nerve
      crush in mice.
AB  - Despite numerous reports suggesting that insulin-like growth factor-I (IGF-I) may
      be involved in the survival and regeneration of damaged neurons in vitro and
      after local administration in vivo, there have been few studies on the effect of
      IGF-I administered systemically on regeneration of damaged nerves in vivo and the
      functional consequences of enhanced regeneration. In an earlier study,
      recombinant human IGF-I (rhIGF-I) administered systemically enhanced the rate of
      regeneration after a sciatic crush as measured by the number of nerve
      fibers/muscle section. The purpose of this study was to follow up this finding by
      evaluating whether rhIGF-I administered peripherally enhances the rate of
      functional recovery. In this study following nerve injury, mice lost the ability
      to grip a wire screen with their hind paws and to walk normally as indicated by a
      decrease in toe spread, internal toe spread and an increase in the angle between
      hind feet. The ability of injured mice treated with rhIGF-I to grip an inverted
      screen returned to control levels significantly faster than that of vehicle
      treated mice (day 12 vs. day 15, respectively). Similarly, rhIGF-I treatment of
      injured mice resulted in toe spread, internal toe spread and angle values that
      were significantly better than that of vehicle-treated mice and returned to
      control levels faster than vehicle-treated injured mice. There was a parallel
      loss of innervation after sciatic nerve crush as measured by a loss in choline
      acetyltransferase activity in the soleus and gastrocnemius muscles.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562521
TI  - Inactivation of Escherichia coli-expressed rabbit cytochrome P-450 2C enzymes by
      17 beta-substituted steroids.
AB  - The specific inactivation of rabbit cytochromes P-450 2C by 17 beta-substituted
      steroids has been investigated by using purified, Escherichia coli-expressed
      enzymes. The expressed P-450s provided a means to characterize accurately the
      effects of 21,21-dichloroprogesterone, 21,21-dichloropregnenolone, 21-chloro-21
      fluoropregnenolone, pregn-5,20-diene-3 beta-ol and pregn-4,20-diene-3-one on
      progesterone hydroxylation by P-450 2C5, 2C4, 2C3 and 2C3v. Previous studies
      using rabbit liver microsomes had suggested that 21-chloro-21-fluoropregnenolone
      is a selective inactivator of 2C5, a progesterone 21-hydroxylase. Studies of the
      expressed P-450 2C forms showed little selectivity of 21,21-dichloroprogesterone,
      pregn-5,20-diene-3 beta-ol or pregn-4,20-diene-3-one, whereas 21,21
      dichloropregnenolone and 21-chloro-21-fluoropregnenolone preferentially
      inactivate 2C5. The data indicate the importance of progesterone 21-hydroxylase
      activity in facilitating selective mechanism-based inactivation of 2C subfamily P
      450s by 21,21-dihalogenated steroids. Studies of the inactivation of P-450 2C16,
      a progesterone 16 alpha-hydroxylase, by the three dihalogenated steroids yielded
      results consistent with previous findings of 16 alpha-hydroxylase inactivation in
      rabbit liver microsomes from the inbred B/J strain. Additionally, two mutants,
      2C3v:V113A and 2C3v:V113A, T364N were created which confer progesterone 21
      hydroxylation on 2C3v. The single mutant, a 6 beta- and 21-hydroxylase, is
      inactivated rapidly by all three of the 21,21-dihalogenated steroids, whereas the
      double mutant, a 16 alpha- and 21-hydroxylase, is preferentially inactivated by
      21,21-dichloroprogesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562522
TI  - Distribution and pharmacokinetics of a potent peptide antagonist of parathyroid
      hormone and parathyroid hormone-related protein in the rat.
AB  - Humoral hypercalcemia of malignancy results from the production by cancer cells
      of parathyroid hormone related protein that activates receptors in bone. Peptide
      antagonists that block parathyroid hormone receptors in vivo would be
      instrumental in the clinical treatment of humoral hypercalcemia of malignancy. We
      report the in vivo whole body distribution and blood plasma pharmacokinetics of
      the parathyroid hormone receptor antagonist [Nle8,18,D-Trp12,monoiodinated
      Tyr34]bPTH(7-34)amide to determine parameters that are likely to affect its
      administration regimen. A single intravenously injected dose of [Nle8,18,D
      Trp12,monoiodinated Tyr34]bPTH(7-34)amide was rapidly cleared from blood plasma.
      The plasma concentration reaches a maximum at 10 min (Cmax = 1.93 +/- 0.27% of
      total injected CPM/ml), and the intact PTH derivative was detectable in plasma by
      HPLC analysis at this time. In vivo binding to plasma proteins was noncovalent.
      The peptide was rapidly cleared from blood by the liver, and more slowly by the
      kidney. Radiolabel was detected in excreted feces at 8 hr, but the preferred
      route of excretion was renal as judged by significant counts in excreted urine.
      Absorption of labeled peptide by skin and bone was sustained. Strong and
      sustained absorption also occurred in the vas deferens, seminal vesicle and
      hypothalamus. Given the rapid clearance of antagonist, multiple or sustained
      dosing schemes might be necessary to achieve the desired pharmacological effect.
      The high counts in liver at early time points after i.v. injection suggest that
      other routes of administration that do not bypass the hepatic first-pass effect
      would result in very low blood levels of drug.

PMID- 7562523
TI  - The pharmacological modulation of angiogenesis in chronic granulomatous
      inflammation.
AB  - Angiogenesis is required for the progression of chronic inflammation, and agents
      that alter it can affect the development of inflammation and the consequent
      tissue destruction. However, in vivo quantification of neovascularization and its
      modulation by angiostatic and angiogenic agents is difficult. Studies have relied
      on reported effects of drugs on embryonic and tumor vasculature to infer
      angiomodulatory actions. We have characterized a vascular casting method that
      incorporates carmine in gelatin. Vascularity expressed as micrograms dye/mg dry
      tissue (vascularity index, V.I.) was studied in the murine chronic granulomatous
      air pouch. Carmine was retained within the vasculature by gelatin, and its
      content increased before the granulomatous tissue, resulting in a V.I. peak at 5
      days, regression and a second peak over 14 to 28 days. The modulation of
      prostaglandin synthesis, plasma exudation and vasomotor tone showed that the
      carmine V.I. remained unaffected, unlike Evans blue, illustrating independence
      from acute inflammatory processes such as vasomotor tone and plasma exudation.
      The angiogenic stimulus p.o. heparin increased the V.I., whereas a sub-anti
      inflammatory dose of cortisone with 1000 U heparin reduced it. Higher doses of
      heparin overcame this. The potent angiostatic steroid tetrahydrocortisol
      significantly reduced the V.I. in the absence of heparin. Cortisone exhibited
      independence from heparin on topical administration in hyaluronan. Dexamethasone
      inhibited granulomatous tissue development with a resulting increase in V.I.
      These observations indicated the differential effects of angiostatic and anti
      inflammatory steroid activity. The pharmacological modulation of angiogenesis in
      inflammation can therefore be quantified.

PMID- 7562524
TI  - Characterization and localization of [125I]RTI-121 binding sites in human
      striatum and medial temporal lobe.
AB  - Dopamine Transporter (DAT) binding sites in medial temporal lobe structures are
      much less dense than in striatum and have been difficult to image and quantitate.
      The recently synthesized compound [125I]RTI-121 ([125I]2 beta-carboxylic acid
      isopropyl ester-3 beta-(4-iodophenyl)tropane) has demonstrated high specificity
      and affinity for the DAT in preliminary animal studies. The present experiments
      were designed to delineate the pharmacological and anatomical characteristics of
      [125I]RTI-121 binding sites in the striatum and medial temporal lobe of normal
      humans. A series of saturation experiments performed with striatal membrane
      preparations generated a one-site model with a KD averaging 1.49 +/- 0.06 nM, and
      a Bmax that was comparable to those of earlier reports. Competition experiments
      confirmed the selectivity of [125I]RTI-121 for DAT binding sites. After the assay
      conditions for autoradiography were optimized, [125I]RTI-121 binding was
      visualized, pharmacologically characterized and quantitated in human temporal
      lobe structures. In the hippocampus, specific binding was distributed in the CA4
      and CA3 pyramidal cell layers, the outer stratum radiatum and the dentate
      molecular layer, but not in the dentate granule cells or outer pyramidal cells.
      In the amygdala specific binding was limited to the basolateral nuclei. Dopamine
      nerve terminals, as identified with [125I]RTI-121 binding, also displayed a
      discrete and homologous innervation pattern in the amygdala and hippocampus of
      several other mammalian species. In summary, the kinetic, saturation, competition
      and autoradiographic experiments demonstrated that [125I]RTI-121 can be used to
      identify DAT binding sites and to assess their functional state in post mortem
      human brain samples.

PMID- 7562525
TI  - Regulation of allosteric coupling and function of stably expressed gamma
      aminobutyric acid (GABA)A receptors by chronic treatment with GABAA and
      benzodiazepine agonists.
AB  - Chronic treatments with drugs that stimulate or potentiate gamma-aminobutyric
      acid (GABA)A receptor function cause uncoupling of allosteric sites and
      downregulation of the GABAA receptors expressed in neurons. To study these
      effects on receptors having a defined subunit composition, we treated stably
      transfected mouse Ltk- cells (PA3 cells) with drugs known to uncouple GABAA
      receptors. Because dexamethasone controls the expression of bovine alpha-1, beta
      1 and gamma 2L GABAA receptor subunit genes in PA3 cells, this expression system
      provides a way to study receptors in the absence of neuronal subunit gene
      promoters. We assayed binding of [3H]flunitrazepam to measure allosteric coupling
      and uptake of 36Cl- to measure GABAA receptor function. Chronic (4 day) treatment
      of PA3 cells with muscimol, GABA or flunitrazepam reduced the GABA enhancement of
      binding of [3H]flunitrazepam to PA3 cells. Chronic flurazepam or muscimol
      treatments also caused downregulation of benzodiazepine potentiation of muscimol
      stimulated 36Cl- uptake. Chronic treatment with muscimol did not affect levels of
      subunit mRNAS and alpha 1- or beta 1-subunit protein of GABAA receptors and
      chronic flunitrazepam did not affect subunit mRNAs or alpha 1 protein. We
      conclude that chronic drug treatments regulate allosteric coupling and function
      of GABAA receptors in stably transfected cells and this regulation cannot be
      attributed to decreases in the expression of receptor subunits or to expression
      of subunits other than alpha 1 beta 1 or gamma 2L.

PMID- 7562526
TI  - Calcium channel activation mobilizes calcium from a restricted pericellular
      region surrounding canine coronary artery smooth muscle cells.
AB  - Functional responses and subcellular calcium redistribution were compared in
      extramural canine coronary arteries to determine the ultrastructural source of
      calcium for depolarization-induced contractions. The subcellular distribution of
      total (bound and free) 45Ca in coronary artery smooth muscle was determined using
      45Ca electron microscopic autoradiography procedures described previously
      (Wheeler-Clark et al., 1986). Relative 45Ca activities were compared for
      ultrastructural regions that included the plasma membrane (PM) region and
      sarcoplasmic reticulum in canine coronary smooth muscle frozen in control and
      high K+ solutions in the presence and absence of 3 x 10(-7) M nitrendipine. The
      45Ca activity of SR was similar in contracted and relaxed muscle cells; thus,
      sarcoplasmic reticulum Ca2+ release was not observed as a result of K(+)-induced
      contraction in canine coronary arteries. However, the 45Ca activity of the PM was
      reduced by 75% in K(+)-contracted cells (P < .05). Inasmuch as nitrendipine
      completely inhibited both contraction and 45Ca loss from the PM region of high
      K(+)-depolarized cells, we suggest that the decreased relative 45Ca activity in
      the PM region of K(+)-contracted cells is due to Ca2+ redistribution from the
      pericellular space into the cytosol during Ca2+ channel activation. Data obtained
      using electron probe x-ray microanalysis also indicate that extracellular Ca2+
      loss was restricted to the pericellular space within 100 nm of the membrane
      bilayer. As a model to explain our data, we suggest that: 1) calcium bound to the
      glycocalyx buffers the free Ca2+ that enters the cell through activated, Ca2+
      channels and 2) a diffusion barrier at the outer edge of the glycocalyx promotes
      and prolongs this calcium buffering.

PMID- 7562528
TI  - Modulation of opioid binding associated with nuclear matrix and nuclear membranes
      of NG108-15 cells.
AB  - Opioid binding sites were found in nuclear matrix preparations from NG108-15
      neurohybrid cells. Binding parameters of delta-specific radioligands indicated
      that high-affinity binding sites discovered in purified nuclei were present in
      nuclear membranes and nuclear matrix fractions. Agonists bind with low affinity,
      if at all, to nuclear matrix preparations. Neither sensitivity of agonist binding
      to the GTP analog 5-guanylylimidodiphosphate nor adenylyl cyclase activity were
      detected in this fraction, suggesting the presence of guanine nucleotide binding
      regulatory protein/effector uncoupled sites. Opioid inhibition of basal and
      forskolin-stimulated adenylyl cyclase activity was found in nuclear membrane
      preparations. Cycloheximide treatment of cells inhibited opioid binding to
      nuclear membrane fractions to a greater extent than that associated with
      membranes sedimenting at 20,000 x g (P20) or nuclear matrix. Colchicine, a
      microtubule disrupter and inhibitor of receptor internalization, caused up
      regulation of nuclear membrane and P20 opioid receptors and a loss in nuclear
      matrix associated sites. Taxol, a microtubule stabilizing agent, prevented the
      effect of colchicine. Etorphine-elicited down-regulation increased nuclear matrix
      associated binding while diminishing that in nuclear membranes and P20 fractions.
      Agonist-induced desensitization completely abolished nuclear matrix binding. In
      vitro preincubation of nuclear matrix preparations with protein kinase A
      catalytic subunit mimicked the desensitization effect. Forskolin treatment of
      cells potentiated nuclear matrix and P20 binding. These data suggest that nuclear
      membrane opioid receptors represent newly synthesized molecules en route to the
      cell surface, whereas nuclear matrix contains internalized delta sites.

PMID- 7562527
TI  - Mechanisms underlying endothelium-independent relaxation by acetylcholine in
      canine retinal and cerebral arteries.
AB  - Canine retinal central arterial strips responded to acetylcholine with a
      relaxation that was endothelium-independent. Indomethacin and atropine abolished
      the relaxation at low doses (10(-7) to 10(-6) M) and moderately attenuated the
      response to high concentrations (10(-5) and 10(-4) M). The residual relaxation at
      10(-5) and 10(-4) M in indomethacin-treated strips were abolished by NG-nitro-L
      arginine, hexamethonium, oxyhemoglobin and methylene blue, and the NG-nitro-L
      arginine-induced inhibition was reversed by L-arginine. Cerebral arterial strips
      with endothelium responded to acetylcholine with a transient relaxation followed
      by a contraction, whereas only a relaxation was induced when endothelium was
      denuded. The relaxations at low and high doses were modified by atropine,
      indomethacin, hexamethonium and NG-nitro-L-arginine quite similarly to those seen
      in retinal arteries. Histochemical study demonstrated the presence of
      perivascular nerves containing NADPH diaphorase in whole mount preparations of
      the retinal artery. It is concluded that acetylcholine-induced retinal arterial
      relaxations, independent of endothelium, are mediated possibly by prostaglandin
      I2 in activation of muscarinic receptors and by nitric oxide derived from
      perivascular nerves in response to nicotinic receptor stimulation. On the other
      hand, vasoconstrictor prostanoids appear to be liberated from the endothelium by
      muscarinic receptor stimulation in cerebral arteries, and mechanisms underlying
      the relaxation are similar to those seen in retinal arteries.

PMID- 7562529
TI  - Role of transforming growth factor-beta 1 on platelet-induced enhancement of
      endothelin-1 production in cultured vascular endothelial cells.
AB  - We and other investigators obtained evidence that platelets stimulate endothelin
      1 (ET-1) production at both message and protein levels in vascular endothelial
      cells (ECs), and that platelet-derived transforming growth factor-beta 1 (TGF
      beta 1) is responsible for this stimulation. In the present study, we examined
      the effects of acidification or heat treatment, known to activate latent TGF-beta
      1, on the platelet supernatant-induced ET-1 production in cultured porcine aortic
      ECs. Supernatant of platelets (6.0 x 10(8) platelets/ml) aggregated by adenosine
      diphosphate contained large amounts of TGF-beta 1, but were almost in a latent
      form, and the proportion of active TGF-beta 1 in the supernatant was increased
      markedly in the case of acidification or heat treatment. These treatments also
      significantly potentiated the supernatant-induced stimulation of prepro ET-1 mRNA
      expression and the ET-1 release in ECs. Purified TGF-beta 1 also enhanced ET-1
      release, dose-dependently, but the enhancement declined at the higher
      concentrations. Thus, powerful stimulation of ET-1 production by platelet
      supernatant after acidification or heat treatment cannot be explained only by
      increments in active TGF-beta 1. The supernatant-induced stimulation of ET-1
      synthesis was significantly inhibited by concomitant treatment of TGF-beta 1
      neutralizing antibody, but this inhibition was incomplete even at a concentration
      that abolished TGF-beta 1-induced maximal stimulation. These results suggest that
      platelet-induced stimulation and subsequent acidification and heat treatment
      induced potentiation on endothelial ET-1 production depend closely on release and
      activation of TGF-beta 1 derived from platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562531
TI  - Regulation of dihydropyridine-sensitive Ca++ channels during opioid tolerance and
      supersensitivity in rats.
AB  - The changes in cerebral dihydropyridine (DHP)-sensitive Ca++ channels (L-type)
      associated with tolerance and supersensitivity to the antinociceptive effect of
      the mu-opioid receptor agonist sufentanil were analyzed in rats. The tail-flick
      test was used to assess the nociceptive threshold. DHP binding and
      autoradiographic assays were performed with [3H]nimodipine and [3H]PN 200-110
      [isopropyl 4-(2,1,3-benzoxadizol-4-yl)- 1,4-dihydro-2,6-dimethyl-5
      methoxycarbonylpyridine-3-carboxylate], respectively. Chronic s.c. infusion of
      sufentanil (2 micrograms/hr) for 7 days induced tolerance (tolerance index, 5.6)
      in association with up-regulation of DHP binding sites in cerebral cortex
      membranes (+36%), as well as in brain sections. Animals were rendered
      hypersensitive to the antinociceptive effect of sufentanil by chronic and
      simultaneous infusion of sufentanil (2 micrograms/hr) and nimodipine (1
      microgram/hr) for 7 days (potentiation index, 40 vs. tolerant). Under these
      conditions, a greater increase in the number of DHP binding sites was observed in
      cortex membranes (+71%), and more evidently in brain sections. In these animals,
      withdrawal of nimodipine for 48 hr returned the dose-response curve of sufentanil
      to the tolerant values, whereas Ca++ channels remained increased. The role of an
      increased influx through L-type channels in opioid tolerance is reinforced. Our
      results also suggest that, although changes in neuronal Ca++ fluxes are not the
      only underlying mechanism, the increase and the sustained blockade of Ca++
      channels with nimodipine is essential for the expression of opioid
      supersensitivity.

PMID- 7562530
TI  - Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel
      nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat
      and nonhuman primate stomach.
AB  - Recent studies have shown that there are two isoforms of cyclooxygenases. The
      constitutive form, cyclooxygenase 1 (COX-1), is believed to be involved in the
      maintenance of physiological functions. A second isoform, cyclooxygenase 2 (COX
      2), has been shown to be induced in inflammation. In the present study, the
      pharmacology of a selective inhibitor of COX-2, L-745,337 (5-methanesulfonamido-6
      (2,4-difluorothiophenyl)-1-indano ne), is described. L-745,337 has IC50 values of
      23 +/- 8 nM and > 10 microM for the inhibition of prostaglandin E2 production in
      whole-cell assays for COX-2 and COX-1, respectively. This compound inhibited
      carrageenan-induced rat paw edema and rat paw hyperalgesia with ID50 values of
      2.00 and 0.37 mg/kg, respectively. In an endotoxin-induced pyresis assay in the
      rat, L-745,337 significantly reversed the pyretic responses (ID50 = 3.75 mg/kg).
      L-745,337 did not cause visible gastric lesions in rats at up to 30 mg/kg (4 hr
      after dosing). In a fecal 51chromium (51Cr) excretion assay to detect
      gastrointestinal integrity in rats and primates, L-745,337 had no effect at doses
      up to 100 mg/kg (rat) or after chronic dosing at 20 mg/kg per day for 5 days
      (primates). In contrast, oral administration of indomethacin, diclofenac or
      flurbiprofen resulted in substantial increase in fecal 51Cr excretion and/or
      frank gastric ulceration (rats). L-745,337 significantly inhibited the
      prostaglandin E2 levels in the inflammatory exudates from the rat pleural cavity
      after injection with carrageenan but did not inhibit prostaglandin E2 levels in
      the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562532
TI  - Mu-opioid receptor regulation during opioid tolerance and supersensitivity in rat
      central nervous system.
AB  - We have analyzed by radiometric procedures in rat central nervous system the
      changes in the properties of mu-opioid receptors associated with tolerance and
      supersensitivity to the opioid agonist sufentanil. This study has used [3H]-[D
      Ala2,MePhe4,Gly- (ol)5(2)]-enkephalin, a highly selective ligand, to label mu
      opioid receptors in both membranes and tissue sections. The induction of opioid
      tolerance by chronic infusion for 7 days of high doses of sufentanil, a high
      efficacy agonist, produced mu-opioid receptor down-regulation, with a significant
      decrease in their density in both cortical (-67%) and spinal cord membranes (
      55%) and no changes in the affinity constant. Autoradiographic studies showed an
      overall decrease of[3H]-Ala2,MePhe4,Gly-(ol)5(2)]-enkephalin binding in the
      somatosensory cortex (around -30%). When the dihydropyridine-Ca++ channel
      antagonist nimodipine was administered alone for 7 days, no significant changes
      in the density or affinity constant of mu-opioid receptors were observed.
      However, the chronic and simultaneous administration of nimodipine and sufentanil
      (7 days), induced a pronounced modification on the density of mu-opioid receptors
      of the rat central nervous system and blocked the down-regulation observed in
      sufentanil-treated (tolerant) rats. These neurochemical findings may account for
      the functional interaction we have observed previously in the analgesic studies
      between nimodipine and sufentanil. Our data strongly suggest a functional role of
      L-type Ca++ channels in the mediation of opioid tolerance and super-sensitivity.

PMID- 7562533
TI  - Selective modulation of elements of the immune system by low molecular weight
      nucleosides.
AB  - To optimally modulate a system as complex as the immune system, one must
      ultimately control its elements individually. Up to this time, use of polyclonal
      immune stimulants has necessarily involved modulation of a block of immune
      functions, frequently including undesired activities as well as the activity of
      interest. We now report selective modulation of individual elements of the immune
      system by low molecular weight nucleosides, within the context of a fully
      functional immune system. Loxoribine (7-allyl-8-oxoguanosine) is a well
      characterized pleiotropic agonist of the immune system in a variety of species,
      including mouse and humans. In B-cells it binds to soluble cytoplasmic binding
      proteins, which upregulate transcription upon translocation to the nucleus. By
      altering specific portions of the loxoribine molecule, multiple distinct,
      bioactivity profiles have now been obtained. These include: 1) selective
      augmentation of antibody responses without effects on B-cell proliferation or NK
      cell activity; 2) selective enhancement of NK-cell activity and B-cell
      proliferation in the absence of antibody responses; and 3) selective enhancement
      of NK-cell activity and antibody responses without B-cell proliferation.
      Predominant NK-cell responses with minimal B-cell activity of either type also
      can be generated. The pattern of cytokine mRNA transcription induced is
      consistent with the spectrum of cellular activities observed. Thus, it is
      possible to modulate selective activities of the immune system by relatively
      minor structural modifications of a broad-spectrum immunomodulator in an
      unseparated cell system.

PMID- 7562535
TI  - Characterization of a delta opioid receptor in rat pheochromocytoma cells.
AB  - In one subclone of PC12 pheochromocytoma cells, PC12h, the levels of delta opioid
      receptors markedly increase in response to nerve growth factor (NGF). This
      increase, as assessed by [3H]diprenorphine binding, is found only under specific
      culture conditions. NGF treatment of PC12h cells also results in the induction of
      delta opioid receptor (DOR-1) mRNA. The time course for NGF induction of mRNA and
      protein is similar, although the levels of mRNA increase approximately 5-fold,
      whereas the levels of receptor increase only 2-fold. Competition studies with
      selective delta ([D-Pen2,5]-enkephalin, DPDPE), mu ([D-Ala2,N-Me-Phe4,Gly-ol5]-
      enkephalin, DAMGO) and kappa (trans-[+/-]-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidinyl)-cyclohexyl]- benzenacetamide methansulfonate salt, U50,488) opioid
      agonists to displace [3H]diprenorphine confirm that the delta subtype of opioid
      receptor is present on PC12h cells. The delta opioid receptor is coupled
      functionally, as indicated by agonist inhibition of forskolin-stimulated cAMP
      accumulation in a naloxone-reversible manner. Finally, the delta opioid receptor
      was cloned from PC12h cells. The sequence was identical with that described
      previously for the rat clone. The PC12h cell line thus provides a model system in
      which to study regulation of delta opioid receptors.

PMID- 7562534
TI  - [3H]-quinelorane binds to D2 and D3 dopamine receptors in the rat brain.
AB  - Quinelorane is a BCD partial ergoline with potent dopaminergic effects in vitro
      and in vivo. Partial ergoline compounds of this series consist of the B-, C- and
      D-rings of the four ring ergoline skeleton. Many of the pharmacological effects
      of quinelorane are believed to be due to stimulation of the D2 subtype of the
      dopamine receptor. Recently, a D3 dopamine receptor was identified that is
      insensitive to guanine nucleotides and exhibits an unusual distribution in the
      brain. When this receptor is expressed in Chinese hamster ovary cells,
      quinelorane has higher affinity for the D3 receptor than the D2 receptor. To
      further define the pharmacology of quinelorane, we have synthesized [3H]
      quinelorane and examined its binding to sections of rat brain in vitro. [3H]
      quinelorane bound with high affinity (KD = 1.8 nM) and exhibited very low
      nonspecific binding. D2 selective antagonists, such as (+)butaclamol and
      spiperone, were potent inhibitors of binding while the D1 antagonist SCH23390 was
      significantly less potent. A majority of the binding was inhibited in a
      concentration-dependent manner by guanylyl-imidodiphosphate with a maximal
      inhibition at concentrations of 1 microM and greater. Autoradiographic studies
      were performed in the presence and absence of 10 microM Gpp(NH)p. Binding in D2
      containing regions, such as the caudate-putamen, was completely inhibited by
      guanylyl-imidodiphosphate although binding in D3 containing areas, such as the
      islands of Calleja, was unaffected. Therefore, [3H]-quinelorane is an excellent
      agonist radioligand for the localization of D2 and D3 receptors in rat brain.

PMID- 7562536
TI  - Antagonism of the discriminative stimulus effects of delta 9-tetrahydrocannabinol
      in rats and rhesus monkeys.
AB  - A newly developed cannabinoid antagonist, SR141716A [N-(piperidin-1-yl)- 5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxa mide
      hydrochloride], binds to brain cannabinoid receptors and has been shown to block
      characteristic pharmacological effects of the aminoalkylindole cannabinoid
      agonist, WIN 55,212-2 (R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpho-
      linyl)methyl]pyrol-(1,2,3-de]-1,4-benzoxazin-6-yl)(1-n aphthalenyl)methanone
      monomethanesulfonate). In the present study, the effects of this compound in an
      animal model of cannabis intoxication were investigated. Rats were trained to
      press one lever after being injected with 3 mg/kg of delta 9-tetrahydrocannabinol
      (delta 9-THC) and to press a second lever after injection with vehicle. Rhesus
      monkeys also were trained to discriminate between delta 9-THC and vehicle.
      Results of tests with various doses of SR141716A in combination with 3 mg/kg of
      delta 9-THC showed that SR141716A produced reversible, dose-dependent antagonism
      of the discriminative stimulus properties of delta 9-THC in rats, with recovery
      within 24 hr. SR141716A also blocked the discriminative stimulus effects of delta
      9-THC in monkeys. Furthermore, in rats, 1 mg/kg of SR141716A produced a 12-fold
      rightward shift in the delta 9-THC dose-effect curve and a 43-fold rightward
      shift in the WIN 55,212-2 dose-effect curve. When SR141716A was administered
      alone, it did not substitute for delta 9-THC in rats. The present results suggest
      that SR141716A blocks the discriminative stimulus effects of delta 9-THC via a
      receptor-mediated mechanism. This drug is the first reliable antagonist of
      cannabinoid discrimination and would be predicted to block or reverse cannabis
      intoxication in humans.

PMID- 7562537
TI  - Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin
      receptor antagonist activity.
AB  - Ziprasidone (CP-88,059) is a combined 5-HT (serotonin) and dopamine receptor
      antagonist which exhibits potent effects in preclinical assays predictive of
      antipsychotic activity. Whereas the compound is a dopamine antagonist in vitro
      and in vivo, its most potent action is antagonism of 5-HT2A receptors, where its
      affinity is an order of magnitude greater than that observed for dopamine D2
      sites. Laboratory and clinical findings have led to a hypothesis that antagonism
      of 5-HT2A receptors in the brain limits the undesirable motor side effects
      associated with dopamine receptor blockade and improves efficacy against the
      negative symptoms of schizophrenia. Ziprasidone possesses an in vitro 5
      HT2A/dopamine D2 receptor affinity ratio higher than any clinically available
      antipsychotic agent. In vivo, ziprasidone antagonizes 5-HT2A receptor-induced
      head twitch with 6-fold higher potency than for blockade of d-amphetamine-induced
      hyperactivity, a measure of central dopamine D2 receptor antagonism. Ziprasidone
      also has high affinity for the 5-HT1A, 5-HT1D and 5-HT2C receptor subtypes, which
      may further enhance its therapeutic potential. The prediction of antipsychotic
      efficacy without severe motor side effects is supported by the relatively weak
      potency of ziprasidone to produce catalepsy in animals, contrasted with its
      potent antagonism of conditioned avoidance responding and dopamine agonist
      induced locomotor activation and stereotypy. The compound is well tolerated in
      animals at doses producing effective dopamine antagonism in the brain.
      Ziprasidone should be a valuable addition to the treatment of psychotic
      disorders.

PMID- 7562538
TI  - Role of Na+ in the asymmetric paracellular transport of 4
      phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg across rabbit colonic
      segments and Caco-2 cell monolayers.
AB  - This study was conducted to demonstrate that Na+ played a role in the
      paracellular transport of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D
      Arg (Pz-peptide), a hydrophilic proline-containing pentapeptide, across the
      rabbit colonic mucosa and Caco-2 cell monolayers. Over the 1 to 5 mM
      concentration range, Pz-peptide transport was 25 to 180 times greater from the
      mucosal-to-serosal than from the opposite direction. This asymmetry in transport
      was consistent with the ability of Pz-peptide to lower the transepithelial
      electrical resistance of Caco-2 cell monolayers only from the mucosal side.
      Blockade of Na+ access to the apically located amiloride-sensitive Na+ channel in
      the lower intestinal segments by mucosal 10 microM amiloride, serosal 100 microM
      ouabain or removal of Na+ ions in the mucosal fluid dramatically reduced Pz
      peptide transport to 5% of the control. Moreover, Pz-peptide transport across
      Caco-2 cell monolayers could be titrated against mucosal Na+ concentration. There
      was a small mucosal-to-serosal solvent drag effect induced by transepithelial Na+
      flux stimulated by Pz-peptide in the colon, contributing in part to enhanced
      paracellular solute transport. Overall, the above findings are consistent with a
      scenario whereby Pz-peptide stimulates transepithelial Na+ flux across the
      colonic segments at the level of the amiloride-sensitive Na+ channel, thereby
      triggering yet to be identified intracellular biochemical changes that ultimately
      result in tight junctional opening and enhanced paracellular solute transport.

PMID- 7562539
TI  - Characterization of endothelin receptors mediating mechanical responses to the
      endothelins in the isolated stomach strip of the rat.
AB  - We have characterized the receptors mediating the mechanical responses of the
      isolated stomach strip to endothelin-1 (ET-1), endothelin-3 (ET-3) and the ETB
      selective receptor agonists sarafotoxin 6c (SX6c) and IRL 1620. As antagonists we
      used BQ-123 (ETA receptor selective), BQ-788 (ETB receptor selective) and PD
      145065 (ETA/ETB receptor nonselective). We have also compared the responses of
      the mature peptides to their precursors human big ET-1(1-38), porcine big ET-1(1
      39) and big ET-3(1-41) amide. ET-1, ET-3, SX6c and IRL 1620 produced equipotent
      concentration-dependent contractions of the rat stomach strips that were
      antagonized by PD 145065 (10(-5) M) or BQ-788 (10(-5) M) but not by BQ-123 (10-5
      M). This indicates that the ETB receptor mediates contractions to the endothelins
      in this preparation. In preparations precontracted with PGE2 (3 x 10(-8) M), ET
      1, but not SX6c (both 3 x 10(-9) M), caused a transient (< 2 min) relaxation
      (approx. 40% of the induced tone). This relaxation was antagonized by BQ-123 (10(
      5) M) but prolonged by BQ-788, and therefore mediated by ETA receptors. A single
      administration of 3 x 10(-7) M ET-1, ET-3, SX6c or IRL 1620 produced contractions
      that reached a maximal response after 1 to 3 min. The contractions were not
      maintained, although responses to ET-1 or ET-3 lost their tone less rapidly than
      those to SX6c or IRL 1620.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562540
TI  - Zatebradine, a specific bradycardic agent, alters the hemodynamic and left
      ventricular mechanical actions of levosimendan, a new myofilament calcium
      sensitizer, in conscious dogs.
AB  - The cardiovascular and left ventricular (LV) functional effects of levosimendan
      were examined (LSM; 0.5, 1.0, 2.0 and 4.0 micrograms.kg-1.min-1) in conscious,
      chronically instrumented dogs (n = 8) in the presence and absence of heart rate
      control with zatebradine (ZAT) or ZAT alone (0.25, 0.5 and 1.0 mg.kg-1). LSM
      increased heart rate (HR) cardiac output (CO), diastolic coronary blood flow
      velocity (DCBFV) and pressure-work index (PWI; calculated myocardial oxygen
      consumption) and decreased mean arterial, LV systolic and end-diastolic
      pressures, systemic vascular resistance and diastolic coronary vascular
      resistance (DCVR). ZAT alone decreased HR and PWI and increased stroke volume.
      LSM-induced increases in HR and PWI were attenuated by ZAT. Increases in DCBFV
      and decreases in DCVR occurred without changes in PWI in the presence of ZAT. LSM
      increased preload recruitable stroke work slope (Mw, 68 +/- 6 to 159 +/- 13 mm
      Hg) and +dP/dt. These positive inotropic effects were partially attenuated by
      ZAT. LSM alone decreased the time constant of isovolumic relaxation (tau, 36 +/-
      2 to 29 +/- 2 ms). LSM-induced decreases in tau were blunted by ZAT, indicating
      that changes in tau were partially dependent on heart rate. LSM increased the
      maximal rate of segment lengthening to a similar degree in ZAT-treated versus 
      untreated dogs. ZAT alone had minimal effects on LV function. Control of LSM
      induced tachycardia with ZAT decreases myocardial oxygen consumption but also
      partially attenuates the positive inotropic and lusitropic effects of LSM.

PMID- 7562541
TI  - Pharmacological characterization of the selective nonpeptide neuropeptide Y Y1
      receptor antagonist BIBP 3226.
AB  - The present study was undertaken to investigate the in vitro and in vivo
      pharmacological profile of the novel, nonpeptide neuropeptide Y (NPY) Y1
      selective antagonist, BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4
      hydroxyphenyl)methyl]-D-arginine-am ide], and a recently described peptidic
      structure [Ile-Glu-Pro-Orn-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic (2,4'), (2',4)
      diamide]. BIBP 3226 antagonized the NPY Y1 receptor-mediated decrease in the
      twitch response in the rabbit vas deferens preparation with a pKb value of 6.98
      +/- 0.06 (n = 16). It showed no affinity (EC50 > 1 microM) for NPY Y2 receptors
      in the rat vas deferens. NPY-induced increases in perfusion pressure in the
      isolated perfused rat kidney and rabbit ear preparations were antagonized with
      IC50 values of 26.8 +/- 4.5 (n = 4) and 214 +/- 30 nM (n = 4), respectively. The
      NPY-mediated potentiation of the noradrenaline elicited increase in perfusion
      pressure in the rat mesenteric bed was antagonized with an IC50 value of 976 (542
      1760) nM. The NPY-induced increase in blood pressure in the pithed rat was
      inhibited by BIBP 3226 dose-dependently (ED50 = 0.11 +/- 0.03 mg/kg i.v.),
      whereas no effect of BIBP 3226 (1 mg/kg i.v.) was observed for the noradrenaline
      , angiotensin-, endothelin- or vasopressin-induced pressor response. The data
      presented demonstrate that BIBP 3226 is a competitive and NPY Y1-selective
      antagonist. The peptidic compound proved to possess high potency for NPY Y1
      receptors, but showed both agonistic as well as antagonistic properties.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562542
TI  - Characterization of nitric oxide generator-induced hippocampal [3H]norepinephrine
      release. II. The role of calcium, reverse norepinephrine transport and cyclic
      3',5'-guanosine monophosphate.
AB  - The mechanisms by which two nitrogen monoxide (NO) generators, hydroxylamine and
      S-nitroso-L-cysteine (NO-CYS), induce hippocampal [3H]norepinephrine ([3H]NE)
      release was investigated. Neither hydroxylamine- nor NO-CYS-induced release was
      affected by the guanylate cyclase inhibitors, methylene blue or LY 83,583. The
      effect of hydroxylamine was completely dependent on extracellular Ca++ and
      reduced by 40% in the presence of omega-conotoxin GVIA, an N-type Ca(++)-channel
      antagonist; however it was unaffected by Ni++, nifedipine, caffeine or
      thapsigargin. The stimulatory effect of hydroxylamine on hippocampal cyclic GMP
      formation was not significantly affected by removal of extracellular Ca++,
      indicating that Ca(++)-dependent release is not due to inhibition of NO formation
      from hydroxylamine. However, the response to NO-CYS was reduced by 35 to 50% in
      either nominally Ca(++)-free or 10 mM MgSO4-containing buffer. Interestingly,
      buffer containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic
      acid dramatically enhanced the formation of NO from NO-CYS and potentiated the NO
      CYS response. Both NO-CYS- and hydroxylamine-induced [3H]NE release was inhibited
      by NE transport blockers, indicating a prominent role for reverse transport. NO
      CYS completely inhibited synaptosomal uptake of [3H]NE (IC50 approximately, 300
      microM). NO generator-induced [3H]NE release has a glutamate-dependent component
      (see accompanying article). Inhibition of glutamate-evoked [3H]NE release by
      mazindol, an inhibitor of NE transport, suggests that the glutamate-dependent
      component also involves reversal of the NE transporter. These data suggest that
      NO produced from hydroxylamine or NO-CYS evoke both vesicular and nonvesicular
      release of hippocampal [3H]NE. Putative NO target molecules and the role of
      extracellular Ca++ are discussed.

PMID- 7562543
TI  - Subtype selectivity and antagonistic profile of the nonpeptide Y1 receptor
      antagonist BIBP 3226.
AB  - In the present study, the subtype specificity and species selectivity of the
      nonpeptide BIBP 3226, as well as its in vitro antagonism of neuropeptide Y (NPY)
      mediated second messengers have been investigated. Radiolabeled NPY is potently
      displaced by BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenylmethyl]-D-
      arginine amide] on human Y1 receptor expressing Chinese hamster ovary-K1 cells
      (Ki = 0.47 +/- 0.07 nM). SK-N-MC human neuroblastoma cells (Ki = 5.1 +/- 0.5 nM)
      and the rat parietal cortex membranes (Ki = 6.8 +/- 0.7 nM). The interaction of
      BIBP 3226 with the Y1 receptor is stereoselective, because the (S)-enantiomer of
      the (R)-configured BIBP 3226 displays almost no affinity (Ki > 10,000 nM). In
      contrast, concentrations up to 10 microM BIBP 3226 do not displace [125I]NPY from
      the human Y2 receptor (neuroblastoma cell line SMS-KAN), the rabbit Y2 receptor
      (kidney) and the rat Y2 receptor (hippocampus). Functional antagonism could be
      shown for the human Y1 receptor: 0.1 microM BIBP 3226 antagonizes the NPY induced
      Ca++ mobilization (pKb = 7.5 +/- 0.17) as well as the NPY-mediated inhibition of
      cyclic AMP synthesis (pKb = 8.2 +/- 0.24) in SK-N-MC cells. In contrast, none of
      the formerly described putative antagonists PYX-2, [D-Trp32]NPY and benextramine
      could be characterized as high affinity Y1 receptor antagonists. The 18 amino
      acid NPY analog EXBP 68 Ile-Glu-Pro-Orn-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic (2,4'),
      (2',4')-diamide] displayed Y1-selective affinity with in vitro antagonistic
      properties (Ki = 0.33 +/- 0.04 nM and pKb = 8.4 +/- 0.07) in SK-N-MC cells.
      Therefore, BIBP 3226 is the first potent and subtype-selective nonpeptide Y1
      receptor antagonist.

PMID- 7562544
TI  - Development of behavioral sensitization to cocaine: influence of kappa opioid
      receptor agonists.
AB  - The effects of acute or repeated administrations of the selective kappa opioid
      receptor agonists U-69593 and U-50488H on cocaine-induced locomotor stimulation
      were examined in the rat. Acute administration of cocaine (10-30 mg/kg i.p.)
      produced a dose-dependent increase in locomotor activity. A single injection of U
      69593 (0.04-0.32 mg/kg s.c.) or U-50488H (2.5-7.5 mg/kg s.c.) administered 15 min
      before cocaine did not modify the effects of an acute cocaine challenge. In
      contrast, repeated administration of U-69593 or U-50488H in combination with
      saline for 3 days prevented the acute locomotor-activating effects of cocaine.
      Repeated administration of cocaine (10-30 mg/kg i.p.) for 3 days resulted in an
      enhancement of its locomotor-activating effects, i.e., sensitization. No such
      sensitized responses were observed in animals that had received U-69593 or U
      50488H in combination with the cocaine treatment regimen. Repeated administration
      of U-69593 (0.16 mg/kg s.c.) for 3 days failed to block the acute locomotor
      activating effects of nicotine (0.6 mg/kg s.c.). Furthermore, when U-69593 was
      given in combination with nicotine, sensitized motor responses to a subsequent
      nicotine challenge were still observed. These data demonstrate that the repeated
      activation of kappa opioid receptors prevents the locomotor activation that
      occurs in response to an acute cocaine challenge as well as the sensitized motor
      responses that develop after the repeated administration of cocaine.

PMID- 7562545
TI  - Schedule-controlled behavioral effects of the selective 2-amino-3-(5-methyl-3
      hydroxyisoxazol-4-yl)propanoic acid antagonist LY293558 in pigeons.
AB  - Behavioral effects of the selective 2-amino-3-(5-methyl-3-hydroxyisoxazol-4-
      yl)propanoic acid (AMPA) antagonist LY293558, along with its racemate (LY215490)
      and opposing enantiomer (LY293559) were evaluated in pigeons. When responding was
      maintained under a multiple fixed ratio 50 responses, fixed interval 5 minute
      (FRFI) schedule of food presentation, LY215490 completely antagonized the rate
      suppression induced by AMPA (10 mg/kg) and by the AMPA analog, 2-amino-3-hydroxy
      5-tert-butyl-4-isoxazolepropionic acid (ATPA; 40 mg/kg) at 1.25 and 2.5 mg/kg,
      respectively. In contrast, LY215490, up to 10 mg/kg, was unable to antagonize the
      rate suppression induced by N-methyl-D-aspartic acid. LY293558, at 0.32 mg/kg,
      completely blocked the rate suppression produced by AMPA in both components of
      the multiple schedule. Similarly, LY293558, at 0.64 mg/kg, blocked the rate
      suppression induced by ATPA in both components. In contrast, the opposing
      enantiomer, LY293559, up to 10 mg/kg, was without effect on rate suppression
      produced by AMPA in this model. In additional studies, behavior was maintained
      under a schedule in which responding was maintained by food presentation in the
      presence of one key color and in the presence of a second key color, responding
      was maintained by food and simultaneously suppressed by electric shock ("punished
      responding"). LY215490 significantly increased punished responding at 10 and 30
      mg/kg, whereas unpunished responding was unaffected until 56 mg/kg depressed it.
      LY293558 significantly increased punished responding at 3 mg/kg without having an
      effect on unpunished responding. LY293559, on the other hand, was unable to
      significantly increase punished responding at doses up to 175 mg/kg.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562546
TI  - New antiinflammatory compounds that inhibit tumor necrosis factor production:
      probable interaction with protein kinase C activation.
AB  - We have previously described a family of benzamide derivatives that showed
      antiinflammatory activity in vivo on carragenin-induced paw edema and
      experimental cerebral edema. Those compounds inhibited eicosanoids production
      from activated macrophages (M phi) without inhibiting cyclooxygenase. To further
      investigate their antiinflammatory activity and compare it to that of classical
      cyclooxygenase inhibitors, we analyzed their effect on the production of a major
      proinflammatory cytokine, tumor necrosis factor (TNF-alpha), by in vitro
      activated peritoneal macrophages. We show that, in marked contrast with
      ibuprofen, flurbiprofen and indomethacin which all significantly enhanced TNF
      production, the two benzamide derivatives tested, JM34 and JM42, significantly
      inhibited TNF-alpha production by zymosan or lipopolysaccharide-activated M phi.
      Those compounds did not interfere with the calcium-dependent pathway because they
      did not affect TNF production of either mice peritoneal M phi or human T cell
      clones induced by the calcium ionophore A23187 alone. More likely, these
      benzamide derivatives acted mainly at the level of the protein kinase C (PKC)
      pathway because: 1) After treatment of M phi with PKC inhibitors which
      significantly inhibited TNF production, our compounds showed no additional
      inhibition. 2) Our compounds significantly inhibited TNF production of M phi
      stimulated with the phorbol ester phorbol di-butyrate alone or in combination
      with A23187. 3) After depletion of PKC by prolonged phorbol di-butyrate treatment
      of M phi, inhibition of TNF production by our compounds was markedly
      decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562547
TI  - Felbamate relieves several abnormal pain sensations in rats with an experimental
      peripheral neuropathy.
AB  - The antiepileptic drug, felbamate, was tested in a rat model of painful
      peripheral neuropathy (the chronic constriction injury model). Intraperitoneal
      doses of 150, 300 and 600 mg/kg were given to animals with established heat
      hyperalgesia, mechanohyperalgesia, mechano-allodynia and signs of spontaneous
      pain (hindpaw guarding). Postinjection tests were conducted 2, 6, 12, 24 and 48 h
      later. The 150 mg/kg dose had little or no effect on any measure. Significant
      reductions in all measures of abnormal pain were seen after the 300 and 600 mg/kg
      doses; relief lasted 2 to 12 h. Side effects were trivial or absent by 2 h
      postinjection. Felbamate's actions were generally antihyperalgesic and
      antiallodynic, rather than analgesic, in that the responsiveness of the control
      (sham-operated) hindpaw was unaffected. We conclude that felbamate suppresses
      neuropathic pain sensations and that its effectiveness may be due to multiple
      mechanisms of action. The recently discovered severe side-effect liability of
      felbamate is likely to preclude its clinical application.

PMID- 7562548
TI  - Drug discrimination analysis of midazolam under a three-lever procedure. II:
      Differential effects of benzodiazepine receptor agonists.
AB  - Twelve rats were trained to discriminate 0.32 and 3.2 mg/kg s.c. midazolam from
      no drug under a three-lever, multiple trials drug discrimination procedure. In
      cumulative dose-response tests, midazolam s.c. (0.032-10 mg/kg) and i.p. (0.1-10
      mg/kg) occasioned dose-dependent increases first in 0.32 mg/kg (low-dose) lever
      responding and then in 3.2 mg/kg (high-dose) lever responding. The
      benzodiazepines diazepam (0.032-18 mg/kg) and triazolam (0.0032-3.2 mg/kg)
      produced patterns of generalization similar to that of midazolam; however,
      chlordiazepoxide (0.1-32 mg/kg), lorazepam (0.032-10 mg/kg), flurazepam (0.01-10
      mg/kg), bretazenil (0.01-32 mg/kg) and the imidazopyridazine zolpidem (0.032-3.2
      mg/kg) dose-dependently occasioned > 80% responding on the low- but not the high
      dose midazolam lever. Clonazepam (0.1-10 mg/kg) occasioned 0% responding on the
      high-dose lever, but also failed to occasion full generalization to the low-dose
      midazolam lever in 40% of the rats. Bretazenil has been well-characterized as a
      partial benzodiazepine agonist and zolpidem as benzodiazepine-receptor-subtype
      selective; the present results are consistent with their partial or selective
      agonist effects in those other paradigms. The differential effects of the classic
      1,4 benzodiazepine agonists tested suggest that the discriminative stimulus
      effects of these other compounds may be more differentiable than previous drug
      discrimination studies have suggested. This three-choice drug discrimination
      procedure appears to be a useful model for studying relative intrinsic efficacies
      of this class of compounds.

PMID- 7562549
TI  - Prophylaxis of genetically determined diabetes by diazoxide: a study in a rat
      model of naturally occurring obese diabetes.
AB  - The study was carried out using a new rat model of naturally occurring obese,
      nonketotic diabetes, Otsuka Long-Evans Tokushima Fatty rat (Kawano et al.,
      Diabetes 41: 1422-1428, 1992), which closely resembles obese noninsulin-dependent
      diabetes in human. At the age of 3.5 wk, body weight, glucose tolerance and
      plasma insulin level after glucose load were normal in Otsuka Long-Evans
      Tokushima Fatty rats, indicating the animals are at nonobese, prediabetic phase.
      At this age, however, glucose-stimulated insulin release by pancreatic islets in
      vitro was abnormally exaggerated whereas the islet insulin content and glucose
      metabolism by the islet cells were normal. Administration of diazoxide (0.2% in
      diet), an inhibitor of insulin secretion, to Otsuka Long-Evans Tokushima Fatty
      rats from the age of 4 to 12 wk completely prevented the development of obesity
      and insulin resistance, which was accompanied by marked improvement of glucose
      tolerance and disappearance of exaggerated B cell response to glucose in vitro.
      This is the first report of successful pharmacological prevention of genetically
      determined obese diabetes.

PMID- 7562550
TI  - Nonpeptide endothelin receptor antagonists. V: Prevention and reversal of acute
      renal failure in the rat by SB 209670.
AB  - The ability of the mixed endothelin (ETA/ETB) receptor antagonist (+/-)-SB 209670
      to prevent and reverse ischemia-induced acute renal failure (ARF) was studied in
      rats with moderate and severe ARF. Uninephrectomized, chronically instrumented
      Sprague-Dawley rats were used. Moderate and severe ARF was induced by occlusion
      of the renal artery for 30 and 45 min, respectively. During the 24 hr after 30
      min ischemia (moderate ARF), glomerular filtration rate (GFR) decreased by 95%,
      and fractional excretion of sodium increased from 0.6% to 10%. Infusion of (+/-)
      SB 209670 at 10, 30 and 100 micrograms/kg.min for 30 min before, during and 60
      min after renal ischemia had a moderate effect on renal function. Thus, with the
      highest dose, the ischemia-induced reduction in GFR was 70%. This dose, however,
      had no effect in rats when given before, during and after 45 min of renal
      ischemia (severe ARF). In contrast, when infused at 30 micrograms/kg.min for 3 hr
      on the day after ischemia, (+/-)-SB 209670 markedly increased survival rate (75%)
      in rats with severe ARF by significantly increasing tubular reabsorption of Na+,
      followed by a slow and gradual increase in GFR and reversal of the increase in
      plasma K+ concentration. Data from acute renal clearance studies in rats with
      moderate ARF showed that when infused 24 hr after ischemia, (+/-)-SB 209670
      acutely reversed the impairment in sodium reabsorption without increasing GFR or
      renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562551
TI  - Modulation by sigma ligands of intracellular free Ca++ mobilization by N-methyl-D
      aspartate in primary culture of rat frontal cortical neurons.
AB  - Despite substantial data on radioligand binding to the sigma receptor, neither
      the physiologic function nor the intracellular mechanism of this receptor is
      known. In this study, we examined the effect of sigma ligands on Ca++ influx
      induced by N-methyl-D-aspartate (NMDA) in single primary cultured rat frontal
      cortical neurons with fluorescence video microscopy. All sigma ligands tested
      reduced the NMDA-induced increase in intracellular Ca++ concentration ([Ca++]i)
      in a dose-dependent manner with IC50 values in the low micromolar range.
      Inhibition by haloperidol and (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1
      ethyl-but-3-en-1-ylam ine hydrochloride (JO1784) was noncompetitive; but,
      exogenous glycine (100 microM) did not alter their IC50 values. In addition,
      haloperidol (1 microM) enhanced Mg+(+)-mediated inhibition of the NMDA-induced
      [Ca++]i increase (IC50 = 0.45 +/- 0.01 mM vs. an IC50 = 0.98 +/- 0.06 mM for Mg++
      alone). Selective sigma receptor ligands (JO1784, (+)-pentazocine) caused a
      greater reduction of the sustained phase of the Ca++ response to NMDA, whereas
      haloperidol and DTG reduced both the initial and sustained phase of the response
      to a similar degree. The rank order of potencies for inhibition of both the
      sustained Ca++ response phase and (+)-[3H]SKF-10047 binding (Roman et al., J.
      Pharm. Pharmacol. 42: 439-440, 1989) were similar. These findings suggest that
      sigma 1 ligands indirectly modulate NMDA receptor complex function through sigma
      1 receptors and that sigma ligands facilitate the desensitization of the Ca++
      response to NMDA.

PMID- 7562552
TI  - The endothelin receptor profile in L6 myotubes.
AB  - In this study we characterized the endothelin (ET) receptors of cultured L6
      myotubes in order to gain a further insight into the mechanism of the ET effect
      on skeletal muscle cells. Displacements of 125I-ET-1 by unlabeled ET-1, ET-2 and
      ET-3 revealed receptors with a high affinity (Kd < 1 nmol/l) to ET-1 and ET-2 and
      a low affinity (Kd > 100 nmol/l) to ET-3, which suggested the presence of
      primarily ETA receptors on L6 myotubes. These findings were complemented by
      displacement binding kinetics, in which the ETA receptor antagonist JKC-301 was
      used. More-over, the ET-1-evoked increase in the cytosolic free Ca was blocked by
      JKC-301 but not by the ETB receptor antagonist IRL-1038. Collectively, these
      findings indicate that the ET-mediated response in cultured skeletal muscle cells
      is through the ETA receptor.

PMID- 7562553
TI  - Intrathecal baclofen and muscimol, but not midazolam, are antinociceptive using
      the rat-formalin model.
AB  - Both gamma-aminobutyric acid (GABA)A and GABAB receptor subtypes have been
      implicated in spinally mediated antinociception in acute pain models. In the
      current study, the formalin test was used as a model of protracted nociception to
      examine the effect of intrathecally (i.t.) administered baclofen (GABAB agonist),
      muscimol (GABAA agonist) or midazolam (a benzodiazepine) on antinociception. At
      doses that did not affect motor function, baclofen (0.3 and 1.0 micrograms, i.t.)
      decreased the flinch response in a dose-dependent manner during Phase 1 and Phase
      2. This effect was reversible by the GABAB-specific antagonist, CGP35348 ([P-(3
      aminopropyl)-P-diethoxymethyl-phosphinic acid]). Muscimol (0.3 and 1.0 microgram
      i.t.) evoked a dose-dependent, bicuculline-reversible decrease in flinching
      during Phase 1 and Phase 2, but midazolam had no effect on either phase. No
      attenuation of the quiescent period between Phase 1 and Phase 2 was seen upon
      administration of baclofen, muscimol or midazolam. Additionally, no increase in
      nocifensive behavior was observed upon administration of either GABAA or GABAB
      antagonists alone. Therefore, our conclusions are that both GABAA and GABAB
      agonists are antinociceptive at the spinal cord level and that endogenous spinal
      GABA levels are insufficient for a GABA potentiator to act alone in an
      antinociceptive manner.

PMID- 7562554
TI  - Effects of cholinesterase inhibitors and clonidine coadministration on rat cortex
      neurotransmitters in vivo.
AB  - In previous investigations, we have demonstrated that cholinesterase inhibitors
      such as physostigmine (PHY) and heptylphysostigmine (HEP) elicit a significant
      and simultaneous increase in acetylcholine (ACh) and norepinephrine (NE) levels
      in the rat cortex. This effect is enhanced by idazoxan, a selective alpha-2
      antagonist. These data suggest that a combination of cholinergic and adrenergic
      drug may improve the pharmacological effect of the cholinesterase inhibitor on
      cortical neurotransmitters such as ACh-NE. In order to obtain additional
      information on cortical cortical neurotransmitter interaction, we tested, in the
      cerebral cortex of the rat, the effect of PHY and HEP in animals pretreated with
      clonidine (CLO), a selective alpha-2 agonist, on ACh, NE, dopamine and 5
      hydroxytryptamine) extracellular levels. We detected no effect of systemic or
      intracortical CLO administration of ACh levels, but NE, dopamine and 5
      hydroxytryptamine levels were all decreased. Systemic coadministration of CLO and
      PHY significantly elevated ACh levels and decreased NE, dopamine and 5
      hydroxytryptamine levels. Systemic coadministration of CLO and HEP produced a
      significant elevation in ACh levels. Comparison between the two treatment
      combinations shows that, although CLO coadministration reduces the effect of PHY
      on ACh levels, HEP administered to animals pretreated with CLO produces a
      stronger effect than HEP alone. A possible explanation for this difference is the
      variation in duration of the two drugs on ACh elevation and muscarinic receptor
      desensitization. As a result of the alpha-2 agonist cholinesterase inhibitor
      coadministration, our data suggest that such a combination does not represent an
      advantage as a therapeutical alternative for treatment of cognitive impairment in
      Alzheimer disease patients.

PMID- 7562555
TI  - Tiapride attenuates pain transmission through an indirect activation of central
      serotonergic mechanism.
AB  - Tiapride dose-dependently attenuated the biphasic nociceptive responses induced
      by s.c. injection of formalin to the hindpaw of mice, and its activity on the
      first (ED50 = 110 mg/kg p.o.) and the second (ED50 = 32.0 mg/kg p.o.) phases
      paralleled that on the nociceptive response to intrathecal injection of substance
      P (ED50 = 190 mg/kg p.o.) and somatostatin (ED50 = 56.0 mg/kg p.o.),
      respectively. Moreover, a similar antinociceptive activity was observed in
      streptozotocin-induced diabetic or genetically diabetic (db/db) mice. The effects
      of tiapride (100 mg/kg p.o.) on both phases of the formalin test in normal mice
      were abolished by pretreatment with p-chlorophenylalanine (800 x 2 mg/kg p.o.), a
      5-hydroxytryptamine (5-HT) depletor, or pindolol (1 mg/kg i.p.), a 5-HT1
      antagonist, but were scarcely affected by 3-tropanyl-indole-3-carboxylate, a 5
      HT3 antagonist. Ketanserin (1 mg/kg i.p.), a 5-HT2 antagonist, attenuated the
      effect of tiapride on the second phase but not on the first phase. This study on
      the antinociceptive mechanism of action of tiapride (that blocks painful
      neuropathy in diabetic patients) has led us to hypothesize that the drug
      attenuates pain transmission through an indirect activation of central 5-HT1 and
      5-HT2 receptors.

PMID- 7562556
TI  - Interactions of dopaminergic and GABAergic neurotransmission: impact of 6
      hydroxydopamine lesions into the substantia nigra of rats.
AB  - We have evaluated (a) the effects of dopamine (DA) denervation on gamma
      aminobutyric acid (GABA) turnover in terms of in vivo rate of GABA synthesis; (b)
      effects of DA D1 and D2 receptor agonists and antagonists on the in vivo GABA
      synthesis rate; and (c) the effects of GABAA and GABAB receptor agonists and
      antagonists on the intracellular accumulation of cAMP in the ipsi- and
      contralateral striatum and substantia nigra of rats after unilateral 6
      hydroxydopamine-induced lesions of the nigrostriatal DA system (DA depletion >
      90%). We observed that the in vivo rate of GABA synthesis remained unaffected
      when the DA levels were depleted by 95% and 50% in the ipsilateral striatum and
      substantia nigra, respectively, compared with the contralateral intact side.
      Basal cAMP levels were increased significantly (92%) in the ipsilateral striatum
      only, compared with the contralateral intact side. The DA D2 agonist quinpirole
      (1.0 mg/kg) significantly decreased the rate of GABA formation in the ipsi- and
      contralateral striatum and substantia nigra. In contrast, the D2 antagonist (+/-)
      sulpiride (25.0 mg/kg) augmented the rate of GABA formation in the DA-denervated
      and intact striatum and substantia nigra. On the other hand, D1 agonist SKF 38393
      (10.0 mg/kg) did not affect the GABA synthesis rate. The in vivo rate of GABA
      synthesis also remained unaffected after administration of D1 antagonist SCH
      23390 (1.0 mg/kg) except in the ipsilateral striatum.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7562558
TI  - Acute amiodarone terminates ventricular fibrillation by modifying cellular Ca++
      homeostasis in isolated perfused rat hearts.
AB  - Intravenous amiodarone has an acute antiarrhythmic action, which may be mediated
      by effects on intracellular calcium concentration [Ca++]i. We evaluated
      termination of pacing-induced ventricular fibrillation (VF) and associated
      changes in [Ca++]i by acute amiodarone in isolated perfused rat hearts loaded
      with the [Ca++]i indicator 1-(2-amino-5-(6-carboxy-2- indolyl)phenoxy)-2-(2-amino
      5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid pentaacetoxymethyl ester.
      [Ca++]i was evaluated with surface fluorometry through fiberoptics placed on the
      interventricular septum. Two minutes after VF induction, hearts were perfused
      with amiodarone (n = 12, 10 micrograms/ml for 5 min followed by 1 micrograms/ml),
      low extracellular calcium concentration [Ca++]o (n = 12, 0.2 mM) or a control
      perfusate (n = 12, no treatment). VF termination during a 30-min observation
      period was significantly more frequent with amiodarone (92%) and with low [Ca++]o
      (75%) compared with no treatment (17%, P < .05). In nontreated hearts without
      recovery, [Ca++]i, expressed as a percentage of the base-line amplitude,
      increased continuously from 206% +/- 44% to 529% +/- 138% during 30-min VF (P <
      .05). In hearts that recovered with amiodarone and low [Ca++]o, [Ca++]i decreased
      significantly from 273% +/- 55% and 273% +/- 99% before treatment to 122% +/- 95%
      and 50% +/- 80% before defibrillation, respectively (P < .05). VF frequency was
      also significantly decreased with amiodarone. The nature of [Ca++]i transients in
      VF has not been fully known. Power spectrum analysis disclosed that [Ca++]i
      transients responded to every one or two electrocardiographic signals in VF with
      the highest frequency of 22 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562557
TI  - Quantification of the in vivo potency of the adenosine A2 receptor antagonist 8
      (3-chlorostyryl)caffeine.
AB  - The purpose of the present study was to quantify the in vivo potency of the
      selective adenosine A2a antagonist CSC [8-(3-chlorostyryl)caffeine]. Four groups
      of conscious, normotensive rats received a continuous i.v. infusion of 0, 6, 12
      and 24 micrograms/min/kg of CSC. During a steady-state infusion of CSC, the
      animals received 1000 micrograms/kg of the adenosine A2a receptor agonist CGS
      21680C [the sodium salt of 2-p-(2-carboxyethyl) phenylethylamino-5'-N
      ethylcarboxamidoadenosine] i.v. over 15 min. During the experiment, the mean
      arterial pressure and the heart rate were recorded continuously and arterial
      blood samples were taken for the analysis of drug concentrations. For each
      individual rat, the CGS 21680C-provoked reduction in blood pressure was related
      to the blood concentration of the agonist according to the sigmoidal Emax model.
      The presence of CSC produced a parallel shift of the concentration-hypotensive
      effect curve to the right, indicating competitive interaction of the compounds.
      Infusion of 0, 6, 12 and 24 micrograms/min/kg of CSC resulted in steady-state
      concentrations of 0, 85 +/- 7, 210 +/- 20 and 400 +/- 40 ng/ml, and apparent EC50
      values of CGS 21680C based on free concentrations (EC50,u) of 4.8 +/- 1.1, 7.2 +/
      0.5, 32 +/- 6 and 57 +/- 10 ng/ml, respectively (mean +/- S.E., n = 6, 6, 5 and
      6). The relationship between the CSC concentration and the apparent EC50 was
      quantified according to a competitive pharmacodynamic interaction model.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562559
TI  - Alpha-2 adrenergic modulation of sleep: time-of-day-dependent pharmacodynamic
      profiles of dexmedetomidine and clonidine in the rat.
AB  - Alpha adrenergic agonists such as clonidine are widely used for their
      antihypertensor effects, but they also cause sedation. The mechanisms underlying
      soporific effects of such compounds are poorly understood, but appear to involve
      the alpha-2 adrenergic receptor sub-type. To further investigate the role of this
      receptor in sleep-wake regulation, rats received injections i.p. either during
      their peak of activity (circadian time CT-18: 6 hr after lights out) or near the
      mid-point of their sleep-dominated phase (CT-5: 5 hr after lights on) with either
      the highly selective alpha-2 agonist dexmedetomidine (dMED) 0.02 to 0.04 mg/kg or
      the less selective alpha-2 agonist, clonidine 0.04 to 0.08 mg/kg, or vehicle.
      Clonidine and dMED showed remarkable overall similarities in their soporific
      profiles. Except for the lower dose of clonidine, both CT-5 and CT-18 treatments
      increased the percent of time spent in non-REM (NREM) sleep. The increase in NREM
      was followed by a reduction of NREM sleep that was accompanied by locomotor
      activity and body temperature above control levels. After CT-5 treatments, this
      period of reduced NREM sleep was followed by a secondary increase in NREM 7 to 10
      hr posttreatment. REM sleep was markedly reduced for 9 to 10 hr after all
      treatments at both times of day, with elevated REM levels 18 to 30 hr
      posttreatment. Pre-treatment with the selective alpha-2 antagonist atipamezole
      (0.5 mg/kg) reversed the effects of CT-18 dMED 0.04 mg/kg except REM sleep
      suppression, which was only partially reversed. The NREM-inducing potency of dMED
      0.02 mg/kg was greater when administered at CT-18 than at CT-5. Taken together
      with other evidence, these findings suggest that the profound NREM-inducing
      effects of dMED may be mediated by postsynaptic alpha-2 adrenoceptors.
      Furthermore, the pharmacodynamic action of alpha-2 adrenergic agonists, like many
      other sedative hypnotics (e.g., benzodiazepines), produce a hysteresis in sleep
      wake regulation characterized by "rebound" waking after drug-induced sleep.

PMID- 7562560
TI  - Microinjection of baclofen in the ventromedial medulla of rats: antinociception
      at low doses and hyperalgesia at high doses.
AB  - Neurons of the nucleus raphe magnus (NRM) and adjacent nucleus reticularis
      gigantocellularis pars alpha (NGCp alpha) receive a tonic inhibitory input from
      gamma-aminobutyric acid (GABA)-ergic neurons that is mediated by GABAA receptors.
      However, comparatively little is known about the role of GABAB receptors in these
      nuclei. The present study examined the effects on nociceptive threshold of
      microinjection of a wide dose range (0.1-150 ng) of the GABAB receptor agonist,
      baclofen hydrochloride (BAC), in the NRM, NGCp alpha or the nucleus reticularis
      giganto-cellularis (NGC). Microinjection of low doses of R(+)-BAC (0.1-1.0 ng) in
      the NRM or the NGCp alpha, but not the NGC increased response latencies in the
      tail flick test. As the dose of BAC was increased to 30.0 to 50.0 ng, response
      latencies in the tail flick test diminished to control values. Microinjection of
      the highest dose, 150 ng, in either the NRM, NGCp alpha or NGC significantly
      decreased response latencies in the tail flick test. Response latencies in the
      hot plate test were not increased by microinjection of 0.1 to 5.0 ng of R(+)BAC
      in the NRM, NGCp alpha or NGC. Although hot plate latency was increased after
      microinjection of 30.0 to 50.0 ng of R(+)-BAC in these nuclei, the effect was
      confounded by the occurrence of motor dysfunction. The effects of BAC were
      stereospecific as nociceptive threshold and motor function were not altered by
      microinjection of either 0.5 ng or 150 ng of the less active stereoisomer, S(-)
      BAC. The biphasic effect of R(+)-BAC suggests the existence of multiple
      mechanisms by which GABAB receptors modulate the activity of neurons in the
      ventromedial medulla. It is proposed that the antinociception produced by low
      doses of R(+)-BAC results from disinhibition (activation) of neurons in the NRM
      and NGCp alpha as a consequence of the presynaptic inhibition of inhibitory
      GABAergic and/or noradrenergic inputs. The decrement in antinociceptive effect
      and hyperalgesia produced by higher doses of R(+)-BAC may result from a
      presynaptic inhibition of excitatory inputs to the NRM and NGCp alpha,
      postsynaptic hyperpolarization of neurons in these nuclei or the unmasking of a
      descending facilitatory pathway originating from the NRM, NGCp alpha and NGC.

PMID- 7562561
TI  - Peptide structural requirements for antagonism differ between the two mammalian
      bombesin receptor subtypes.
AB  - Recently it has been established that both a gastrin-releasing peptide (GRP)
      receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin
      related peptides in mammals. Five different classes of peptides that function as
      GRP receptor antagonists have been identified; however, it is unknown whether
      similar strategies will yield antagonists for the closely related NMB receptor.
      In the present study we have used either native cells possessing only one
      bombesin (Bn) receptor subtype or cells stably transfected with one subtype to
      determine whether using the strategies that were used successfully for GRP
      receptors would allow NMB receptor antagonists to be identified. [DPhe12]Bn
      analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides;
      and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all
      synthesized and each functioned as a GRP receptor antagonist. All of these
      antagonists had low affinity for the NMB receptor. Application of similar
      strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des
      Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor
      antagonists. D-Amino acid SP and SP(4-11) analogs were weakly selective NMB
      receptor antagonists. No COOH-terminal fragments of NMB or GRP functioned as a
      GRP or NMB receptor antagonist. These results demonstrate that none of the known
      strategies used to prepare peptide GRP receptor antagonists are successful at the
      NMB receptor, suggesting that a different strategy will be needed for this
      peptide, such as the formation of somatostatin octapeptide or D-amino acid
      substituted substance P analogs. These results suggest that even though there is
      a close homology between GRP and NMB and their receptors, their structure
      function relations are markedly different. These results indicate that the
      development of receptor subtype-specific peptide agonists or peptide antagonists
      for newly discovered receptor subtypes of gastrointestinal
      hormones/neurotransmitters may be difficult because the strategies developed for
      one well-studied subtype may not apply to the other even though it is
      structurally closely related.

PMID- 7562562
TI  - Hepatic transport of rose bengal by perfused rabbit liver: the effect of albumin
      binding on the unidirectional rate constants.
AB  - The effect of albumin on the unidirectional rate constants for the hepatic
      transport of rose bengal was studied using perfused rabbit livers. Rabbit livers
      were perfused in a recirculating system with albumin concentrations between 10
      and 600 microM and the disappearance of I-125 rose bengal following a bolus
      injection was recorded. A distributed model of hepatic transport was used to
      estimate the rate constants for influx into cells, efflux from cells to plasma
      and biliary excretion. When the rate constants were corrected for albumin
      binding, the influx, but not the efflux or excretion constant, was a steeply
      rising function of the perfusate albumin concentration. The result that the
      influx but not efflux constant is albumin dependent suggests that the phenomenon
      is not due to slow diffusion across an unstirred fluid layer or to nonequilibrium
      binding within such a layer. The possibility that the albumin-dependent influx is
      due to a direct exchange of rose bengal between albumin and a membrane carrier
      protein is also considered. The independence of the efflux constant and the
      albumin concentration makes this hypothesis less tenable. However, these data are
      consistent with the facilitation of albumin-ligand dissociation by liver cells.
      This analysis represents the first reduction to practice of distributed modeling
      of disappearance curves. The fact that the excretion constant is independent of
      the perfusate albumin concentration serves to validate the model that has
      previously only been considered on theoretical grounds.

PMID- 7562563
TI  - Interactions of nifedipine with the renovascular effects of endothelin in humans.
AB  - Infusion of endothelin-1 in humans to obtain pathophysiological plasma levels
      causes mild hypertension, strong sodium retention and renal vasoconstriction.
      Animal studies have shown that part of these effects depend upon activation of
      voltage-dependent calcium channels. However, it is unknown whether hemodynamic
      effects of endothelin-1 in humans, once established, can be reversed by calcium
      channel blockers. We therefore studied in healthy subjects whether coinfusion of
      nifedipine, after 60 min of endothelin-1 infusion, could reverse these effects.
      During endothelin-1 infusion alone, plasma endothelin increased from 2.9 +/- 0.2
      to 8.0 +/- 0.6 pmol/l (P < .05). Blood pressure rose by approximately 6 mm Hg at
      the end of the endothelin-1 infusion (P < .05). Endothelin-1 caused a marked
      increase in renal vascular resistance by approximately 34% (P < .05) and in
      filtration fraction by approximately 25% (P < .05). Sodium excretion decreased
      from a base-line value of 144 +/- 25 to 81 +/- 15 mumol/min at the end of the
      endothelin infusion (P < .05). During coinfusion of nifedipine, plasma endothelin
      levels increased to similar values as found during endothelin-1 infusion alone.
      Blood pressure increase was prevented, whereas the increase in renal vascular
      resistance and antinatriuresis were reversed completely. However, nifedipine
      could not reverse the endothelin-induced increase of filtration fraction,
      indicating that the effects of endothelin-1 and nifedipine in the renal
      microcirculation do not overlap completely. Because calcium channel blockers have
      a preferentially preglomerular effect, this suggests that endothelin-1 maintained
      vasoconstriction of the efferent arteriole in the kidney during
      nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562564
TI  - Potent and selective inhibitors of leukotriene A4 hydrolase: effects on purified
      enzyme and human polymorphonuclear leukocytes.
AB  - Leukotriene (LT) A4 hydrolase (EC 3.3.2.6) is a bifunctional zinc metalloenzyme
      that catalyzes the hydrolysis of the unstable epoxide intermediate LTA4 into the
      proinflammatory substance LTB4 and also exhibits an amidase/peptidase activity
      toward synthetic substrates. Based on proposed reaction mechanisms for other zinc
      hydrolases, we have synthesized inhibitors of LTA4 hydrolase and evaluated their
      effects on the formation of LTB4 from LTA4 using both purified enzyme and intact
      polymorphonuclear leukocytes. The two most effective inhibitors, an alpha-keto
      beta-amino ester (compound IV) and a thioamine (compound VIII), exhibited IC50
      values of 1.9 +/- 0.9 and 0.19 +/- 0.12 microM (mean +/- SD, n = 4),
      respectively. Compounds IV and VIII were also potent inhibitors of LTB4
      biosynthesis in ionophore stimulated polymorphonuclear leukocytes with IC50 < 200
      nM. At higher concentrations, the biosynthesis of 5-hydroxy-eicosatetraenoic acid
      was also inhibited with IC50 approximately 10 microM for both substances. In
      contrast, leukocyte 15-lipoxygenase and platelet LTC4 synthase activity were not
      inhibited by these substances at the highest concentrations tested, 50 and 10
      microM, respectively. Compounds IV and VIII thus exhibit selectivity among enzyme
      activities in the arachidonic acid cascade. In conclusion, we describe two
      compounds that are among the most potent and selective inhibitors of LTA4
      hydrolase and LTB4 biosynthesis by intact polymorphonuclear leukocytes, described
      thus far.

PMID- 7562566
TI  - Arachidonic acid cascade and stimulation of acetylcholine release by human
      recombinant interleukin-1 beta in guinea pig ileum.
AB  - We examined the effect of interleukin 1 beta (IL-1 beta) on enteric cholinergic
      neuronal activity in the isolated guinea pig ileum. Pretreatment with human
      recombinant IL-1 (hr IL-1) (100-1000 pg/ml) for 15 to 60 min potentiated
      contractions of the ileum induced by electrical transmural stimulation (ETS) (1
      Hz, 1 msec, for 1 min) in a time- and concentration-dependent manner, hrIL-1 beta
      (300-1000 pg/ml) potentiated the ETS- (1 Hz, 1 msec, for 2 min) evoked release of
      [3H]acetylcholine (ACh) from entire preparations of ileum preloaded with
      [3H]choline, but not from longitudinal-myenteric plexus preparations and mucosa
      free preparations, in a time- and concentration-dependent manner. The maximum
      effect of IL-1 beta on both responses was obtained 60 min after exposure to 1000
      pg/ml IL-1 beta. hrIL-1 alpha had no effect on the contractions and [3H]ACh
      release induced by ETS. The boiled hrIL-1 beta and the hrIL-1 beta absorbed with
      anti-hrIL-1 beta antibody failed to potentiate the ETS-evoked release of [3H]ACh.
      Cycloheximide (100 micrograms/ml), mepacrine (10(-6) M), indomethacin (3 x 10(-6)
      M) and nordihydroguaiaretic acid (10(-5) M) inhibited the potentiating effect of
      IL-1 beta, with no effect on the ETS-evoked release. Thus, IL-1 beta stimulates
      enteric cholinergic neurons through the arachidonic acid cascade produced in
      tissues other than longitudinal muscle and myenteric plexus of the guinea pig
      ileum.

PMID- 7562565
TI  - Leukotriene C4 receptors on guinea pig tracheocytes.
AB  - Leukotriene (LT) C4 receptors have been characterized on freshly isolated guinea
      pig tracheal epithelial cells (tracheocytes). The [3H]LTC4 receptor affinity was
      enhanced by increasing the sodium (60-160 mM) and the magnesium (0-10 mM)
      concentrations. Low concentrations of calcium (0-3 mM) increased [3H]LTC4
      binding, but high concentrations (3-10 mM) decreased it. The pH (6.5-8.0) had no
      effect on [3H]LTC4 binding to tracheocytes. Under our experimental conditions,
      binding equilibrium was reached after 20 min. The association and the
      dissociation rate constants were estimated to be 2.75 +/- 0.25 x 10(6) M-1.min-1
      and 0.093 +/- 0.008 min-1, respectively. The Kd (35.4 +/- 8.6 nM) and the Bmax
      values (2.4 +/- 0.6 x 10(5) receptors/cell) were determined by Scatchard
      analysis. LTB4, LTD4 and LTE4 did not inhibit [3H]LTC4 binding to the receptors.
      However, the compound FPL 55712 inhibited the binding of [3H]LTC4 with an IC50
      value of 9.0 +/- 1.0 microM. [3H]LTC4 was not metabolized during the binding
      assays, as confirmed by reverse-phase high-performance liquid chromatography. The
      lack of [3H]LTC4 binding to glutathione-S-transferase was demonstrated in the
      presence of an excess of reduced glutathione. LTC4 produced a concentration
      dependent increase of free Ca++ in tracheocytes. Our results suggest that guinea
      pig tracheocytes possess a specific LTC4 receptor coupled to a Ca++ signaling
      pathway. This LTC4 receptor may play a key role in the epithelium-dependent
      responses of airway smooth muscle.

PMID- 7562567
TI  - Age-dependent sensitivity of rats to the long-term effects of the serotonergic
      neurotoxicant (+/-)-3,4-methylenedioxymethamphetamine (MDMA) correlates with the
      magnitude of the MDMA-induced thermal response.
AB  - The effects of developmental age on (+/-)-3,4-methylenedioxymethamphetamine
      (MDMA)-induced reductions in 5-hydroxytryptamine (5-HT) content and 5-HT reuptake
      sites were investigated in conjunction with the effects of developmental age on
      MDMA-induced thermoregulatory responses. MDMA was administered to rats at
      postnatal days (PND) 10, 40 and 70 in a range of ambient temperature environments
      (10 degrees C, 25 degrees C and 33 degrees C). Animals were monitored for
      alterations in body temperature and sacrificed 1 week after MDMA administration.
      MDMA administration at PND 10 did not result in persistent reductions in 5-HT
      content or 5-HT reuptake sites in frontal cortex, nor could a hyperthermic
      response be elicited. In contrast, MDMA administration at PND 40 and PND 70
      resulted in a hypothermic response in cold environments (10 degrees C) and a
      hyperthermic response in warm environments (> or = 25 degrees C). When
      hypothermia was observed after MDMA (10 degrees C environment), long-term
      reductions in 5-HT content and 5-HT reuptake sites were significantly attenuated
      or abolished. Conversely, when a hyperthermic response was observed (25 degrees C
      and 33 degrees C environments), long-term MDMA-induced reductions in 5-HT content
      and 5-HT reuptake sites were significantly enhanced. Thus, thermal responses
      significantly correlated with MDMA-induced reductions in 5-HT content and 5-HT
      reuptake sites. These experiments demonstrate a role for hyperthermia in the
      expression of serotonergic neurotoxicity after MDMA administration.

PMID- 7562568
TI  - Opioid modulation of fetal glucose homeostasis: role of receptor subtypes.
AB  - Opioids have long been known to influence glucose homeostasis in the adult.
      However, their role in modulating glucose regulation in the fetus is not known.
      The objectives of this study were to determine the effects of morphine on fetal
      plasma glucose levels and to ascertain the role of opioid receptor subtypes in
      fetal glucose homeostasis. The studies were carried out in 38 unanesthetized
      fetal sheep (123-142 days) (term being approximately 145 days). Intravenous
      infusion of morphine to the fetus resulted in dual actions on fetal plasma
      glucose, with hypoglycemia after 1.2 mg/hr (F3,16 = 6.02; P = .006; n = 5) and
      hyperglycemia after 5.0 mg/hr (F3,16 = 5.58; P = .008; n = 5). Significant
      increase in plasma lactate concentration also was found after 5.0 mg/hr (F3, 16 =
      5.25; P = .010). Both hypoglycemia and hyperglycemia were antagonized by i.v.
      naloxone, indicating both were mediated by specific opioid receptors. The mu
      selective agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (100 micrograms/hr
      i.c.v., n = 6), resulted in a significant increase in both plasma glucose (F3,20
      = 11.50; P = .001) and lactate (F3,20 = 3.77; P = .007) concentrations. In
      contrast, the delta-selective agonists, [D-Pen2,D-Pen5]-enkephalin (30 and 100
      micrograms/hr i.c.v.) and [D-Ala2]-deltorphin I (0.3 and 1.0 micrograms/hr
      i.c.v.) had no effect on plasma glucose or lactate levels. Similarly, Dynorphin
      A(1-13) (160 and 480 micrograms/hr i.c.v.) and U50,488H [trans-(+/-)-3,4-dichloro
      N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide] (200 micrograms/hr
      i.c.v.) also had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562569
TI  - Preventive effect of rebamipide on gastric lesions induced by ischemia
      reperfusion in the rat.
AB  - Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid),
      a novel antiulcer agent, has been reported to prevent various acute experimental
      gastric mucosal lesions and to accelerate the healing of chronic gastric ulcers.
      We investigated the effect of rebamipide on rat gastric mucosa damaged by
      exposure to 30 min of ischemia and 60 min of reperfusion (I/R) with continuous
      intragastric instillation of 0.1 N HCl (1 ml/100 g body weight) into the stomach.
      Rebamipide, at 30 and 100 mg/kg, i.p., reduced the mucosal damage score from 2.28
      (I/R vehicle group) to 1.54 and 1.07, respectively. Pretreatment with rebamipide
      significantly reduced the activity of myeloperoxidase (an index of neutrophil
      infiltration) and preserved the activities of superoxide dismutase and nitric
      oxide synthase in the gastric mucosa with inhibition of malondialdehyde
      production. Thus, a negative correlation between the activities of nitric oxide
      synthase and myeloperoxidase (y = 4.35-9.45x, r = .67, P < .01) was observed. In
      an in vitro study, rebamipide inhibited N-formyl-met-leu-phe-induced chemotaxis
      of neutrophils and production of superoxide anion from opsonized zymosan
      stimulated neutrophils. However, it did not affect the production of superoxide
      anion either by the xanthine-xanthine oxidase reaction or phorbol 12-myristate 13
      acetate-stimulated neutrophils. Based on these results, it is suggested that
      rebamipide exerts a protective effect on the I/R-induced gastric mucosal damage
      through inhibition of mobilization and activation of neutrophils in association
      with an attenuation of the decreases in both superoxide dismutase and nitric
      oxide synthase activities, thereby preventing the gastric microcirculation from
      deterioration.

PMID- 7562570
TI  - Cocaine sensitization in periadolescent and adult rats.
AB  - Periadolescent rats have been reported to be affected differentially by
      catecholaminergic agents when compared with younger or adult animals. The present
      study evaluated the behavioral responsivity of periadolescent (34- to 39-day-old)
      and adult (60- to 70-day-old) Sprague-Dawley rats of both sexes to i.p. cocaine
      (Coc) administration (0, 10 or 20 mg/kg, once daily for 4 days). All animals
      received injections of both saline and Coc every day paired with a different
      context, with one-half of the animals receiving the drug in the home cage (Coc
      Home) and the other half in the testing chamber (Coc-Test). Forty-eight hours
      after the last drug injection, all animals were challenged with 10 mg/kg i.p. of
      Coc, and their behavior in the test chamber was scored. As expected, acute Coc
      induced a prominent increase in a number of behaviors, and this response profile
      was less marked in periadolescent relative to adult animals. In contrast, Coc
      Test animals of both ages showed a clear behavioral sensitization relative to the
      chronic saline group. No evidence of carry-over effects was found in Coc-Home
      animals. Females were in general more sensitive than males to acute Coc effects.
      The development of behavioral sensitization to Coc was a function of age-specific
      alterations in sensitivity to psychostimulants. Periadolescent rats of both sexes
      showed sensitization to the locomotor activating effects (matrix crossings) of
      Coc, whereas a consistent sensitization profile for both stereotyped head
      scanning and focused sniffing activities were found in adults but not in
      periadolescents. Chronic Coc reduced body weight and food consumption,
      particularly in adult males, whereas it did not affect periadolescent patterns.
      No evidence of sensitization to Coc was found in the hormonal parameters
      considered.

PMID- 7562571
TI  - Effect of the 5-hydroxytryptamine3 receptor antagonist itasetron (DAU 6215) on
      (+)-N-allylnormetazocine-induced dopamine release in the nucleus accumbens and in
      the corpus striatum of the rat: an in vivo microdialysis study.
AB  - The in vivo brain microdialysis technique has been used to study the ability of
      itasetron, [DAU 6215, (3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide
      hydrochloride], a novel 5-hydroxytryptamine3 (5-HT3)-receptor antagonist, to
      antagonize the effect of the sigma-agonist (+)-N-Allylnormetazocine (SKF 10,047)
      in inducing the release of dopamine from mesolimbic and nigrostriatal
      dopaminergic neurons, in comparison with haloperidol and clozapine. SKF 10,047
      caused a dose-dependent increase in the release of endogenous dopamine
      preferentially from the nucleus accumbens septi with respect to the corpus
      striatum of the rat, the time to peak being 60 min from its administration.
      Itasetron (1-30 micrograms/kg s.c. given 45 min before SKF 10,047 5 mg/kg s.c.)
      dose dependently antagonized the SKF 10,047 response in the nucleus accumbens
      septi and not in the corpus striatum, without inducing by itself changes of basal
      DA output in either area at these doses. Another selective 5-HT3 receptor
      antagonist, ondansetron, at the dose of 10 micrograms/kg s.c., like itasetron,
      blocked the SKF 10,047-induced release of dopamine. At the dose of 100
      micrograms/kg s.c., both itasetron and ondansetron failed to modify the effect of
      SKF 10,047 and increased DA release per se in the nucleus accumbens septi.

PMID- 7562572
TI  - Preferential binding of the novel prostaglandin SC-46275 to canine gastric versus
      intestinal receptors.
AB  - Prostaglandins (PGs) in the E-series exhibit potent gastric antisecretory
      activity, but can also cause diarrhea, which is mediated via PGE receptors. SC
      46275, an omega-chain cyclopentenyl analog of the E-type PG enisoprost, was
      evaluated with other E-PGs for PGE receptor binding activity in gastric and
      intestinal tissues. SC-46275, enisoprost, misoprostol and PGE1 were first
      evaluated in enriched canine gastric parietal cells with [3H]misoprostol free
      acid binding and subsequently with [3H]PGE1 binding in canine intestinal tissues
      where misoprostol free acid had weak receptor binding activity. The receptor
      binding potency of SC-46275 (IC50, 0.013 mM) in enriched canine parietal cell
      preparations was found to be much greater than misoprostol and enisoprost (IC50,
      10 and 8 nM), whereas PGE1 had the least potency (IC50, 37 nM). Similar relative
      potencies for these PGs were also obtained in the inhibition of histamine
      stimulated acid secretion in enriched parietal cell preparations. In small
      intestinal mucosal and muscle membranes, the receptor binding potency of SC-46275
      (IC50, 13 and 20 microM) was much less than misoprostol or enisoprost (IC50, 0.39
      1.2 microM) and substantially less than PGE1 (IC50, 0.017 and 0.066 microM). This
      weak binding activity of SC-46275 in intestinal tissues is consistent with its
      reported weak diarrheagenic activity in the rat. These results suggest that SC
      46275 binds preferentially to gastric vs. intestinal PGE receptors and is
      specific for the EP3 receptors.

PMID- 7562573
TI  - Agonist and antagonist effects of dynorphin A-(1-13) in a thermal antinociception
      assay in rhesus monkeys.
AB  - The agonist and antagonist effects of intravenously administered dynorphin A-(1
      13) were characterized in the warm water (50 and 55 degrees C) tail withdrawal
      assay of antinociception in rhesus monkeys. The peptide dose-dependently elevated
      tail withdrawal latencies in 50 degrees C water, but was ineffective in 55
      degrees C water. The antinociceptive effect of dynorphin was surmountably
      antagonized by quadazocine (0.1 mg/kg) and nor-binaltorphimine (3.2 mg/kg), but
      was not antagonized by clocinnamox (0.1 mg/kg); this pattern of antagonism is
      consistent with a kappa-opioid receptor mediated effect. Pretreatment with
      dynorphin A-(1-13) (0.032-3.2 mg/kg) antagonized the antinociceptive effects of
      U50,488 and U69,593 in 55 degrees C water, suggesting a low efficacy action of
      the peptide at the receptors activated by these kappa agonists. However,
      dynorphin A-(1-13) (3.2 mg/kg) did not antagonize other kappa agonists:
      bremazocine (0.018-0.056 mg/kg) and enadoline (0.0056-0.018 mg/kg). Taken
      together, these dynorphin A-(1-13) findings support the notion of functional
      kappa-opioid receptor subtypes, and it appears that dynorphin A-(1-13) has
      limited efficacy at one of these sites. Finally, dynorphin A-(1-13) (0.32 mg/kg)
      also antagonized the antinociceptive effects of the mu-agonist etonitazene
      (0.0018-0.01 mg/kg).

PMID- 7562575
TI  - Microinfusion of mu but not delta or kappa opioid agonists into the basolateral
      amygdala results in inhibition of the tail flick reflex in pentobarbital
      anesthetized rats.
AB  - Recent evidence suggests that certain forms of opioid-mediated hypoalgesia may
      depend on monosynaptic projections from the amygdala to nociceptive modulatory
      neurons in the midbrain. We recently demonstrated that the microinjection of
      morphine sulfate into the basolateral nucleus of the amygdala will result in a
      robust elevation of radiant heat tail flick (TF) latency in the pentobarbital
      anesthetized rat. The present study was conducted to begin to clarify the opioid
      receptor type(s) responsible for this effect. Rats were anesthetized with sodium
      pentobarbital and prepared for microinfusion and TF testing. Rats received
      simultaneous bilateral infusions of agonists for mu ([D-Ala2, N-MePhe4, Gly-ol 5]
      enkephaphalin (DAMGO); 0.01, 0.05, 0.1, 1.0 or 5.0 micrograms), delta ([D-Pen2, D
      Pen5]enkephalin [DPDPE]; 6.458 or 64.58 micrograms) or kappa (trans-3,4-dichloro
      N-methyl-N-(2-(1-pyrolidinyl)-cyclohexyl)-benz ene acetamide methanesulfonate
      hydrate [U50, 488H]; 5.0, 40.0 or 84.0 micrograms) opioid receptors during TF
      testing. The mu agonist produced a dose- and time-dependent elevation in TF
      latency when injected into the basolateral amygdala. Application of the delta and
      kappa agonists to similar sites within the amygdala was without effect. In
      separate experiments, U50, 488H and DPDPE were injected into the lateral
      ventricle at concentrations similar to those applied to the amygdala.
      Intracerebroventricular administration of these compounds resulted in reliable
      inhibition of TF. These results indicate that mu opioid receptors in the
      basolateral amygdala may be able to modulate transmission in a recently
      identified neural circuit that is at least partially responsible for the
      expression of stress-related hypoalgesia in behaving animals.

PMID- 7562574
TI  - Effects of single and multiple intravenous cocaine injections in humans
      maintained on methadone.
AB  - The effects of i.v. cocaine were examined in individuals maintained on methadone.
      Sixteen adult methadone-maintained i.v. cocaine users, residing on a clinical
      research unit, participated in eight laboratory sessions under each of two
      conditions: cocaine 1 hr after daily methadone and cocaine 22 hr after daily
      methadone. The conditions were separated by an outpatient period of 3 to 5 weeks.
      During the first five sessions, the cardiovascular and subjective effects of
      single i.v. cocaine doses (0, 8, 16, 32 or 48 mg/70 kg) were determined. During
      the last three sessions, the effects of i.v. cocaine (0, 8 or 32 mg/70 kg)
      administered 4 times per session at 14-min intervals were determined. Single and
      repeated doses of cocaine produced dose-dependent increases in cardiovascular
      effects (e.g., diastolic pressure and heart rate), subjective effects (e.g.,
      ratings of "High," or "Stimulated") and ratings of cocaine dose (e.g., "Quality,"
      or "Liking"), regardless of methadone dose or the timing of cocaine
      administration. Increases in blood pressure after single cocaine doses were
      greater when cocaine was given 1 hr after methadone. Subjects maintained on
      higher methadone doses (> 60 mg) reported larger cocaine effects after single
      doses on several measures including ratings of Liking and Stimulated. Finally,
      the opiate symptom scores after cocaine administration were 100% larger than
      those observed previously after cocaine administration to opiate-experienced, but
      not dependent, individuals. These data suggest that any improvement in cocaine
      abuse observed in methadone-maintained individuals is not related to a blocking
      of the subjective effects of cocaine, and that higher methadone doses could have
      a negative impact on cocaine abuse in some individuals.

PMID- 7562576
TI  - Actions of the benzopyran compound terikalant on macroscopic currents in rat
      ventricular myocytes.
AB  - The putative Class III antiarrhythmic benzopyran compound terikalant (RP62719)
      has been applied to isolated rat ventricular myocytes. The drug, at extracellular
      concentrations from 1 to 60 microM, reduced the inactivation time constant of
      transient outward potassium current (I(to)) with the time constant decreased to
      50% of the control value with terikalant at 11 microM. The peak value of I(to)
      was also diminished with terikalant in excess of 2 microM and analysis of the
      integral of charge movement showed this quantity to be halved with a drug
      concentration near 5 microM. The voltage dependence for both activation and
      inactivation of I(to) were not changed by terikalant and the drug had no effect
      on the time course of recovery from inactivation. The inhibition of I(to)
      currents was increased with time during depolarizing pulses suggesting drug
      interactions with the open channel and analysis of the time dependence of drug
      block gave estimates of 3.7 x 10(6) M-1 s-1 and 64 s-1 for the respective
      blocking and unblocking rate constants. At concentrations greater than 5 microM,
      terikalant also altered the peak amplitudes of inward rectifier K+ currents (IK1)
      elicited with hyperpolarizing or depolarizing steps from holding potential and
      diminished IK1 resulting from voltage ramps. The results of this study represent
      the initial characterization of terikalant actions in a species possessing
      abundant I(to) in ventricular myocytes.

PMID- 7562577
TI  - Time- and concentration-dependent biphasic effect of ochratoxin A on growth of
      proximal tubular cells in primary culture.
AB  - Ochratoxin A (OTA) leads to trophic and functional changes in the proximal tubule
      of the kidney. We investigated the effects of micromolar and nanomolar
      concentrations of OTA on cell growth, cell viability and transepithelial
      transport in rat proximal tubular cells in primary culture. Micromolar
      concentrations of OTA exerted a hypotrophic and hypoplastic effect after 24 hr,
      but a hypertrophic and hypoplastic effect after 72 hr. These effects could be
      abolished in a concentration-dependent manner by the addition of albumin to the
      medium. In parallel, micromolar concentrations reduced cell viability, monolayer
      integrity and abolished the formation of transepithelial gradients of Na+ and K+.
      Nanomolar concentrations of OTA had neither hypotrophic nor hypertrophic effects,
      but stimulated DNA synthesis and cell division, leading to hyperplasia. At the
      same time, nanomolar concentrations did not reduce cell viability or the
      formation of electrolyte gradients. Lowering extracellular pH to 6.8 abolished
      the effect of nanomolar concentrations of OTA on DNA synthesis and cell number as
      well as the effect of micromolar concentrations on cellular protein. Cellular
      alkalinization (pH 7.7) also stimulated proliferation, but did not act additively
      with nanomolar concentrations of OTA. From these results, we conclude that OTA
      exerts a time-dependent biphasic effect on cellular protein content and a
      concentration-dependent biphasic effect on DNA synthesis. The stimulatory effect
      is independent of its toxic action. Modulation of both effects by extracellular
      pH suggests that cellular pH-homeostasis may be involved in the action of OTA.

PMID- 7562578
TI  - Comparison of benzodiazepine receptor ligands with partial agonistic,
      antagonistic or partial inverse agonistic properties in precipitating withdrawal
      in squirrel monkeys.
AB  - Benzodiazepine receptor (BZR) ligands previously characterized as differing in
      intrinsic efficacy were evaluated first for potency in antagonizing flunitrazepam
      induced sleep in monkeys. Data from these experiments were used to define
      approximately equieffective doses for subsequent use in precipitating withdrawal
      in diazepam-treated monkeys. It was shown that partial agonists with intermediate
      intrinsic efficacy (bretazenil, Ro 41-7812) were relatively ineffective in
      precipitating withdrawal reactions in diazepam-treated squirrel monkeys. The
      potent and specific BZR antagonist flumazenil, which possesses weak intrinsic
      efficacy, was more effective in precipitating a withdrawal reaction in diazepam
      treated monkeys. In contrast, the highest dose of the BZR antagonist ZK 93426
      that could be administered failed to precipitate withdrawal under the same
      experimental conditions. Finally, the BZR partial inverse agonist sarmazenil was
      the most effective of these BZR ligands in eliciting a precipitated withdrawal
      reaction. Thus, the results of the present investigation strongly suggest that
      BZR ligands differing in intrinsic efficacy differentially precipitate withdrawal
      in squirrel monkeys treated chronically with diazepam.

PMID- 7562580
TI  - Changes in sympathetic neurotransmission and adrenergic control of cardiac
      contractility during 1,3-dipropyl-8-sulfophenylxanthine-induced hypertension.
AB  - We have explored the hypothesis that systemic hypertension induced by long-term
      treatment with the purinoceptor antagonist 1,3-dipropyl-8-sulfophenylxanthine
      (DPSPX) might be associated with functional modifications of the adrenergic
      mechanisms of control of cardiac performance comparable to those described in
      other models of hypertension. Seven days continuous i.p. infusion of rats with
      DPSPX (30 micrograms/kg/hr) significantly increased systolic blood pressure. When
      sympathetic neurotransmission was evaluated via electrical field stimulation of
      atrial tissue, contractile responses were significantly reduced in hypertensive
      animals compared to controls. Similarly, contractile responses to exogenous
      norepinephrine were attenuated in tissue from hypertensive animals, thus
      suggesting that DPSPX treatment affects cardiac sympathetic neurotransmission via
      postjunctional rather than prejunctional changes. Inotropic responses of
      ventricular myocardium to both alpha- and beta-adrenoceptor stimulation were also
      significantly reduced in DPSPX-treated tissue. The responsiveness of atrial and
      ventricular myocardium to adenosine was unaffected by DPSPX treatment. The
      present study indicates that DPSPX-induced hypertension is associated with
      altered adrenergic regulation of the cardiac function that results in reduced
      inotropic responses of both atrial and ventricular myocardium to endogenous
      norepinephrine, as well as to adrenoceptor agonists applied exogenously. These
      alterations are comparable to those described in other models of genetic or
      induced hypertension, thus supporting the view that purinergic mechanisms may
      contribute to the onset and development of systemic hypertension.

PMID- 7562579
TI  - Repeated stimulation of dopamine D2-like receptors: reduced responsiveness of
      nigrostriatal and mesoaccumbens dopamine neurons to quinpirole.
AB  - Extracellular recording techniques were used to study antidromically activated
      nigrostriatal (NSDA) and mesoaccumbens (MADA) dopamine neurons in chloral hydrate
      anesthetized rats. Repeated 14-day i.p. treatment with the dopamine D2-like
      receptor agonists, quinpirole (2 mg/kg/day) or EMD 23448 (2.6 mg/kg/day),
      resulted in a significant decrease in the average potency and efficacy of i.v.
      quinpirole (cumulative doses administered on day 15) to inhibit the spontaneous
      activity of NSDA neurons relative to vehicle controls. Repeated 14-day quinpirole
      treatment caused a significantly greater decrease in the sensitivity of MADA
      neurons to i.v. quinpirole challenges than NSDA neurons. When the effects on NSDA
      neurons were examined after a shorter treatment period, the decrease in the
      average potency and efficacy of i.v. quinpirole appeared to occur after only 2
      days of i.p. quinpirole treatment (2 mg/kg/day). Iontophoretic studies, however,
      indicated that the average dopamine sensitivity of somatodendritic dopamine
      autoreceptors on MADA neurons, but not NSDA neurons, was significantly lower
      relative to controls after 14-day quinpirole treatment (2 mg/kg/day). These
      results suggest that this quinpirole treatment regimen can differentially affect
      the average sensitivity of somatodendritic dopamine autoreceptors on MADA and
      NSDA neurons. The somatodendritic autoreceptors on MADA neurons appear to be more
      sensitive to the effects of repeated 14-day quinpirole treatment than those on
      NSDA neurons.

PMID- 7562581
TI  - Necessity of newly synthesized ATP by creatine kinase for contraction of
      permeabilized longitudinal muscle preparations of rat proximal colon.
AB  - Necessity of newly synthesized ATP by creatine kinase for synthesis of ATP as an
      energy source for smooth muscle contraction was studied in permeabilized
      longitudinal muscle preparations of rat proximal colon. In alpha-toxin
      permeabilized preparations, Ca++ induced "phasic type" contraction in a normal
      bath solution containing 4 mM ATP and 5 mM phosphocreatine. Omission of
      phosphocreatine from the solution resulted in significant decrease in phasic
      contraction, and omission of ATP resulted in loss of the response to Ca++. When
      ADP, but not adenosine-5-O-(2-thiodiphosphate), with phosphocreatine was added as
      a substitute for ATP, Ca++ induced the same type of contraction as with ATP. The
      maximum tensions of the phasic and tonic phases of the contraction with ADP were
      approximately 60% of, and almost the same, respectively as those with ATP. A
      selective inhibitor of creatine kinase, 2,4-dinitrofluorobenzene, inhibited the
      phasic contraction induced by Ca++. After irreversible inhibition of endogenous
      creatine kinase by DNFB in beta-escin-permeabilized preparations, treatment of
      the preparations with exogenous creatine kinase restored Ca(++)-induced
      contraction. These findings suggest that ATP synthesized from ADP and
      phosphocreatine by creatine kinase was necessary for phasic contraction of
      permeabilized smooth muscle and that exogenous ATP was mainly used after its
      hydrolysis to ADP.

PMID- 7562582
TI  - Distribution of morphine 6-glucuronide and morphine across the blood-brain
      barrier in awake, freely moving rats investigated by in vivo microdialysis
      sampling.
AB  - Microdialysis was used to sample morphine 6-glucuronide (M6G) and morphine in
      striatal extracellular fluid after systemic administration in awake, freely
      moving rats. Morphine or M6G (25-67 mumol/kg) was given subcutaneously, and blood
      and striatal dialysate were sampled repeatedly during 120 min. Blood samples were
      obtained by indwelling catheters in the inferior vena cava. Opiates in serum or
      brain dialysate were analyzed with high-performance liquid chromatography. The
      functional intactness of the blood-brain barrier was verified by the use of
      sodium technetate (Na99mTcO4). The fractional penetration into the brain of
      morphine and M6G was approximately 350- and 90-fold higher than that of
      Na99mTcO4, respectively, with a relative difference in the transfer of morphine
      and M6G of about 4. No hydrolysis of M6G to morphine was detected. Striatal
      dialysate-to-serum ratios of M6G did not differ after 25 or 67 mumol/kg. Serum
      AUC0-120 min was 10 times higher for M6G than for morphine. This reflects both a
      smaller volume of distribution (Vd) for M6G and a decreased rate of elimination
      compared with morphine. The median t1/2 from serum was 36 and 32 min for morphine
      and M6G, respectively. The striatal dialysate AUC0-120 min of M6G was 2.9 times
      greater than that of morphine after an equimolar subcutaneous dose. Dialysate
      tmax was delayed approximately 40 min relatie to serum tmax for both drugs, and
      the median t1/2 from the dialysate was 82 and 48 min for M6G and morphine,
      respectively. These results represent direct evidence for the penetration of M6G
      into the brain after systemic administration to living rats.

PMID- 7562583
TI  - Reversal of cyclosporine A-induced alterations in biliary secretion by S-adenosyl
      L-methionine in rats.
AB  - This study examines the ability of S-adenosyl-L-methionine to prevent or
      antagonize the cyclosporine A-induced adverse effects on biliary secretion in the
      rat. S-adenosyl-L-methionine was administered as a single bolus 3, 5 and 8 hr
      before administering a single dose of cyclosporine A, and also concurrently
      administered with cyclosporine A for 1 or 2 wk. Acute S-adenosyl-L-methionine
      preadministration attenuated the cyclosporine-induced cholestasis and inhibition
      of bile acids, cholesterol and phospholipid biliary secretion. S-adenosyl-L
      methionine pretreatment for 1 wk and simultaneous cotreatment with cyclosporine
      for 1 or 2 wk not only maintained the beneficial effects reported above but
      further improved them because the adverse effects of the immunosuppressor drug
      were prevented or antagonized by S-adenosyl-L-methionine. These results provide
      the first direct evidence of the ability of exogenously administered S-adenosyl-L
      methionine to antagonize cyclosporine-induced abnormalities in biliary bile
      acids, lipids and protein secretion. The beneficial effects of S-adenosyl-L
      methionine could be related, at least in part, to the improvement in the
      hepatobiliary transport of bile acids.

PMID- 7562584
TI  - TEI-3313, a novel prostaglandin A1 derivative, prevents bone loss and enhances
      bone formation in immobilized male rats.
AB  - The effect of a novel prostaglandin A1 derivative, TEI-3313, with the chemical
      structure 5-[(Z,2E)-4,7-dihydroxy-2-heptenyridene]-4-hydroxy- 2-methylthio-4-(4
      phenoxybutyl)-2-cyclopentenone, on bone mineral content was investigated. Seven
      week-old Sprague-Dawley rats in which the right hindlimbs were immobilized by
      sciatic nerve dissection received 1, 10, 100 or 500 micrograms of TEI
      3313/kg/day, i.p., for 6 weeks. Control animals were operated on but received
      vehicle only. Bone mineral content of the femur was measured by single-photon
      absorptiometry, and biochemical parameters were analyzed. Histomorphometric
      observations were performed on the proximal metaphysial sections of the tibiae.
      The administration of up to 500 micrograms/kg of TEI-3313 to rats had no effect
      on body weight or on serum calcium, inorganic phosphorus and 1 alpha,25 dihydroxy
      vitamin D3 levels. Immobilization decreased the ash content, calcium content and
      total bone mineral content of the femur compared with nonimmobilization
      (unoperated femur). With TEI-3313 administration, changes in these parameters in
      the immobilized femur were prevented almost to the levels of the nonimmobilized
      femur, in a dose-dependent manner. The enhancement of bone mineral content was
      remarkable in the midshaft of the femur. TEI-3313 enhanced ash and calcium
      content and total bone mineral content in nonimmobilized femurs. Microradiograms
      showed that TEI-3313, unlike pamidronate and 17 beta-estradiol, had little
      inhibitory effect on trabecular bone resorption in the proximal portion of the
      tibia. TEI-3313 not only prevented the bone loss induced by immobilization but
      also increased bone mass in the nonimmobilized femurs without affecting the
      levels of 1 alpha,25 dihydroxy vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562585
TI  - Different molecular forms of basic fibroblast growth factor (bFGF) accelerate
      duodenal ulcer healing in rats.
AB  - Basic fibroblast growth factor is an angiogenic polypeptide that exhibits potent
      antiulcer activity without decreasing gastric acid or pepsin secretion. In this
      study, we investigated the effect of three acid-stable derivatives of human
      recombinant bFGF (hrbFGF) on the healing of chronic duodenal ulcer in rats. In
      Sprague-Dawley female rats, duodenal ulcers were induced by cysteamine-HCl. After
      laparotomy, rats were randomized to create six groups with homogeneously severe
      ulcers (perforated or penetrated into the liver or pancreas) and treated by
      gavage twice a day for 3 weeks with a) vehicle, b) cimetidine (10 mg/100 g), c)
      Ser78,96-hrbFGF (bioequivalent to rbFGF-CS23), d) CMC-hrbFGF, a carboxymethyl
      cysteine derivative of hrbFGF or e) PEG-hrbFGF, a polyethylene glycol derivative
      of hrbFGF. The peptides were administered at 100 ng/100 g. Autopsy was performed
      on the 21st day, and the ulcer size was measured. The ulcer sizes (mm2) were
      reduced from 10.3 +/- 1.8 in controls to 4.8 +/- 1.4* after cimetidine treatment
      and to 5.0 +/- 2.4, 4.2 +/- 1.1* and 0.5 +/- 0.2**, respectively, after
      administration of aforementioned hrbFGF derivatives (*P < .05; **P < .01 vs.
      vehicle group), which also significantly enhanced angiogenesis in the ulcer bed.
      CONCLUSIONS: 1) Oral administration of novel derivatives of hrbFGF accelerated
      the healing of cysteamine-induced chronic duodenal ulcer. 2) The PEG-hrbFGF
      derivative was more active than the other hrbFGF analogs. 3) The naturally
      occurring bFGF provides a good prototype to design new locally acting antiulcer
      drugs.

PMID- 7562586
TI  - In vitro pharmacokinetics of phosphorothioate antisense oligonucleotides.
AB  - ISIS 2105 (Afovirsen), a 20-mer phosphorothioate oligonucleotide that inhibits
      the production of a gene product essential to the growth of human papillomavirus,
      is in phase II clinical trials for the treatment of genital warts induced by
      human papillomavirus-6 and human papillomavirus-11. The uptake, subcellular
      distribution and metabolism of ISIS 2105 and three other similar length
      phosphorothioates have been studied in a variety of cell lines. Our experiments
      indicated that ISIS 2105 and other phosphorothioates are internalized and
      distributed in a time-, temperature-, concentration-, sequence- and cell line
      dependent manner. Cell association was also influenced by the tissue culture
      medium. Several different analytical techniques revealed that phosphorothioates
      were more rapidly degraded in vitro than previously reported. These data suggest
      that phosphorothioate oligonucleotide uptake and stability observed in tissue
      culture can vary as a function of cellular assay conditions and analytical
      methods used. Comparison of these results with those obtained in vivo suggests
      that the pharmacokinetic behavior of this class of compounds cannot necessarily
      be predicted from in vitro studies.

PMID- 7562587
TI  - Prevention and reduction of neural damage in ischemic strokes by w-(N,N'
      diethylamino)-n-alkyl-3,4,5-trimethoxybenzoate compounds.
AB  - Experimental ischemic stroke was induced by an occlusion of middle cerebral
      artery and common carotid artery of rats for 60 min. The occlusion was then
      released and the extent of neural damage was measured by the estimation of
      necrosis areas where the dead neurons lost their ability to take up triphenyl
      tetrazolium chloride. w-(N,N'-Diethylamino)-n-alkyl-3,4,5-trimethoxybenzoate
      (TMB) compounds are calcium antagonists capable of reducing intracellular free
      calcium through inhibition of calcium release from the sarcoplasmic reticulum.
      These compounds were found to prevent and/or reduce neural damage effectively.
      When the animals were pretreated with TMB-2, TMB-5 and TMB-8, 1 hr before
      ischemia, the areas of neural necrosis were reduced almost completely by 95%, 99%
      and 92%, respectively. When these TMB compounds were given at 0 time and 1 hr
      after ischemia, the prevention of necrosis was almost complete also. However,
      when TMB-2, TMB-5 and TMB-8 were administered 6 hr after ischemia, the necrosis
      areas were reduced less effectively by 83%, 78% and 91%, respectively. TMB
      compounds were also found to increase cAMP and to reduce intracellular free
      calcium concentration. These results indicate that TMB compounds are effective
      calcium antagonists to prevent/treat ischemic stroke by reducing the
      intracellular free calcium through reduction of calcium release from sarcoplasmic
      reticulum.

PMID- 7562588
TI  - Induction of apoptosis in murine and human neuroblastoma cell lines by the
      enediyne natural product neocarzinostatin.
AB  - Neocarzinostatin (NCS) is a naturally occurring enediyne antitumor agent that
      produces single- and double-strand breaks in cellular DNA. We have previously
      shown that treatment of human (SK-N-SH) and murine (NB41A3) neuroblastoma cells
      with NCS results in cell death for a subpopulation within the culture. The
      remaining cells undergo mitotic arrest with morphological differentiation along
      glial lines. Further investigation of cell death induced by this agent
      demonstrates that within 24 hr after a single one hr exposure to submicromolar
      concentrations of NCS, susceptible cells of both lines decrease in size, round
      up, detach from the culture surface and fragment in the overlying medium. This
      cytotoxicity is attenuated by the addition of cycloheximide (in NB41A3 cells) or
      aurintricarboxylic acid (in NB41A3 and SK-N-SH cells). Fluorescence and electron
      microscopic examination of the nonadherent cells reveals the chromatin
      condensation and fragmentation characteristic of apoptosis. Examination of the
      time course of DNA cleavage reveals that despite the presence of alkaline elution
      detectable DNA cleavage, oligonucleosomal-sized DNA fragments are not
      demonstrable by gel electrophoresis immediately after a 1-hr incubation with the
      drug (1.6-10,000 nM). However, by 6 hr after treatment, DNA ladders are in
      evidence at all concentrations of NCS. These results suggest that the
      oligonucleosomal cleavage of DNA seen after NCS treatment is associated with
      apoptosis, rather than being the direct result of the strand-cleaving effects of
      the drug itself.

PMID- 7562589
TI  - Interactions between hydroxocobalamin and nitric oxide (NO): evidence for a redox
      reaction between NO and reduced cobalamin and reversible NO binding to oxidized
      cobalamin.
AB  - Interactions of nitric oxide (NO) with various cobalamin species have been
      examined, apparently for the first time, with both absorption and electron
      paramagnetic resonance spectroscopy. Only slight shifts in the absorption
      spectrum of hydroxocobalamin, B12a [Cb(III)], were produced by NO, but dramatic
      changes in the spectrum of B12r [Cb(III)] were found on addition of NO. The
      addition of NO shifted the spectrum of Cb(II) to one very similar to that of
      Cb(III), indicating the oxidation of Cb(II). The addition of NO to Cb(III)
      resulted in a novel, weak and previously undescribed electron paramagnetic
      resonance signal. Although it has not been fully characterized, this appears to
      represent a reversible complex in which NO is liganded to the Cb(III). When NO
      was added to Cb(II), its strong electron paramagnetic resonance spectrum was
      replaced by that of this novel species, consistent with oxidation of Cb(II) by NO
      and then binding of additional NO by the resulting Cb(III). Porcine, aortic
      endothelial cells were able to partially reduce Cb(III), and release to the
      supernatant a previously characterized superoxide cobalt(III) complex, but some
      Cb(II) remained with the cell fraction. These reactions of Cb species could play
      a role in altering intracellular and intratissue levels of NO.

PMID- 7562590
TI  - Peripheral and central cholecystokinin receptors regulate postprandial intestinal
      motility in the rat.
AB  - Postprandial cholecystokinin (CCK) has been suggested as an important mediator of
      disruption of migrating myoelectric complexes (MMC) after a meal. However, the
      role of CCK in regulating small intestinal motility in rats and the participation
      of central and/or peripheral CCK-A and B receptors in CCK actions, are still
      unclear. For this study, Sprague-Dawley rats were prepared with electrodes in the
      small intestine, a catheter in the jugular vein and an intracerebroventricular
      (i.c.v.) cannula. Postprandial disruption of the MMC was blocked by the i.v.
      infusion of the CCK-B antagonist L-365,260 (2 x 10(-7) mol/kg), but not by the
      infusion of the CCK-A antagonist L-364,718. When administered i.c.v., L-364,718
      (2.25 x 10(-9) mol), but not L-365,260, restored the MMC pattern. The i.v.
      infusion of CCK-8 (1-3 x 10(-9) mol/kg) or CCK-4 (10(-7) mol/kg) disrupted the
      MMC pattern. CCK-8 effects where prevented by the i.v. infusion of either L
      364,718 or L-365,260. Administered i.c.v., only the antagonist L-364,718
      prevented CCK-8 disruption of the MMC. These results suggest that CCK-mediated
      motor changes after a meal are due to stimulation of peripheral CCK-B receptors.
      CCK also induces a release of central CCK that through CCK-A receptors
      participates on MMC disruption.

PMID- 7562591
TI  - Roles of prostaglandins, nitric oxide and the capsaicin-sensitive sensory nerves
      in gastroprotection produced by ecabet sodium.
AB  - We determined the mechanism of the gastroprotective effects of ecabet sodium
      (ecabet), a new antiulcer drug. Ecabet (12.5-100 mg/kg p.o.) dose-dependently
      protected gastric mucosa from ethanol-induced injuries in rats, as determined
      with the use of both macroscopic and microscopic analyses. Both inhibition of
      prostaglandin (PG) formation by indomethacin (5 mg/kg s.c.) and functional
      ablation of capsaicin-sensitive sensory nerves (CPSN) by systemic administration
      of capsaicin (125 mg/kg s.c.) partly reduced the gastroprotective activity of
      ecabet (25 and 100 mg/kg p.o.). Ecabet increased rat gastric mucosal PGE2
      formation. The treatment with indomethacin but not capsaicin decreased the ecabet
      induced increase in PGE2 formation. Inhibition of nitric oxide (NO) formation by
      NG-monomethyl-L-arginine (L-NMMA; 100 mg/kg i.v.) partly reversed the
      gastroprotective effect of ecabet and completely reversed that of capsaicin at an
      oral dose of 0.5 mg/kg, respectively. The effect of L-NMMA was abolished by
      pretreatment with L-arginine (100 mg/kg i.v.) but not with D-arginine (100 mg/kg
      i.v.). The gastroprotective activity of ecabet (25 mg/kg p.o.) was fully reversed
      by pretreatment with indomethacin in combination with L-NMMA or CPSN ablation. On
      the contrary, a combination of L-NMMA and CPSN ablation did not have additional
      effect on the suppression by either treatment alone. These findings indicate that
      the gastroprotection by ecabet is cooperatively mediated by endogenous PGs and
      CPSN-related endogenous NO.

PMID- 7562592
TI  - 5-Hydroxytryptamine-induced synovial plasma extravasation is mediated via 5
      hydroxytryptamine2A receptors on sympathetic efferent terminals.
AB  - 5-Hydroxytryptamine (5-HT) is known to act in peripheral tissues to produce pain
      and inflammation, yet the mechanisms underlying 5-HT-induced inflammation have
      not been well studied. The present study uses a rat knee joint model of
      inflammation (synovial plasma extravasation) and molecular biological techniques
      to determine the site of action of 5-HT and the specific 5-HT receptor subtype
      mediating synovial 5-HT-induced plasma extravasation. 5-HT (1 microM) stimulates
      synovial plasma extravasation 7-fold above base-line levels. Surgical lumbar
      sympathectomy, but not C-fiber depletion by neonatal capsaicin, dramatically
      reduces 5-HT-induced synovial plasma extravasation (P < .001), indicating that
      sympathetic efferents mediate this effect. Polymerase chain reaction
      amplification of 5-HT receptor cDNA demonstrates that 5-HT1A, 5-HT1B, 5-HT1D, 5
      HT2A and 5-HT3, but not the 5-HT2C, receptor subtypes are present in lumbar
      sympathetic ganglia. With selective ligands for these receptor subtypes, we
      demonstrate that 5-HT-induced synovial plasma extravasation is mediated via the 5
      HT2A receptor. These findings suggest a role for 5-HT2A antagonists in various
      synovial inflammatory pain states.

PMID- 7562593
TI  - Chronic antidepressant treatment facilitates G protein activation of adenylyl
      cyclase without altering G protein content.
AB  - It has been suggested that the molecular basis of antidepressant action involves
      postreceptor components. Results from our studies have suggested that a G protein
      (Gs) is one of those targets and that chronic antidepressant treatment
      facilitates the activation of adenylyl cyclase by Gs alpha. This report
      represents an attempt to define which aspects of G protein function are altered
      by chronic antidepressant treatment. Rats were treated for 21 days with
      amitriptyline, desipramine, ABT 200 (a pyrollidine with putative antidepressant
      effects) or electroconvulsive shock, and membranes were prepared from the
      cerebral cortexes. Each of these treatments caused an increase in membrane
      adenylyl cyclase assayed in the presence of guanyl-5'-imidodiphosphate (> or = 1
      microM). Results of acute antidepressant treatments were no different than those
      of control treatment. Chronic treatment with amphetamine, which inhibits
      neurotransmitter reuptake without displaying antidepressant effect, was also
      ineffective in increasing Gs alpha stimulation of adenylyl cyclase. Chronic
      antidepressant treatment did not change the content of G protein, as no change at
      the level of Gs alpha, Gi alpha, Go alpha or G beta protein was detected by
      immunoblotting. Although there was no change in the amount of G proteins,
      antidepressant treatment increased the number of active Gs alpha/adenylyl cyclase
      complexes immunoprecipitated by an anti-Gs alpha antibody. It is suggested that
      chronic antidepressant treatment alters certain membrane components such that a
      greater proportion of Gs alpha is activated, Gs alpha enjoys a more fruitful
      interaction with adenylyl cyclase, or both.

PMID- 7562594
TI  - Distribution of the mu and delta opioid binding sites in the brain of the alcohol
      preferring AA and alcohol-avoiding ANA lines of rats.
AB  - There is experimental evidence indicating that the positive reinforcing effects
      of ethanol, responsible for voluntary ethanol consumption, are in part mediated
      by the endogenous opioid system. Differences in some components of the endogenous
      opioid system have been observed between lines and strains of animals bred
      selectively for their high or low ethanol consumption. Our objective was to
      investigate the presence of differences in the density and distribution of mu and
      delta opioid receptors in the brain of the alcohol-preferring Alko-Alcohol and
      alcohol-avoiding Alko, NonAlcohol lines of rats using iodinated ligands specific
      for mu ([D-Ala2, MePhe4, Met(o)ol5]-Enkephalin (FK 33-824)) or for delta ([D
      Ser2]-leucine enkephalin-Thr) opioid receptors. Results calculated from studies
      on membrane preparations of whole brain minus cerebellum indicated that the Bmax
      and Kd were similar between the two lines of rats; however, autoradiographic
      studies showed that the alko-alcohol rats presented significantly higher density
      of mu opioid receptors in some brain regions, including nuclei of the limbic
      system that are important in mediating the reinforcing properties of many drugs
      of abuse. Furthermore, studies on brain membrane preparations indicated that both
      lines of rats were deficient in high affinity delta binding sites compared to
      Sprague-Dawley rats. Indeed, autoradiographic studies confirmed the presence of
      low density of the high affinity binding sites for [D-Ser2]-leucine enkephalin
      Thr in both lines of rats. However, the density of the high affinity delta
      binding sites was higher in some distinct brain regions of the Alko-Alcohol than
      Alko-NonAlcohol rats. These differences in the density of both mu and delta
      opioid receptors may be partially responsible for the differences in voluntary
      ethanol consumption exhibited by these two lines of rats.

PMID- 7562595
TI  - Noradrenergic involvement in the discriminative stimulus effects of cocaine in
      squirrel monkeys.
AB  - Noradrenergic involvement in the discriminative stimulus (DS) effects of cocaine
      was investigated in squirrel monkeys by using a two-lever drug discrimination
      procedure in which responding was maintained by a fixed-ratio schedule of
      stimulus-shock termination. Monkeys initially were trained to discriminate a
      relatively high dose of cocaine (1.0 mg/kg i.m.) from saline and subsequently
      were retrained to discriminate a 3.3- to 5.6-fold lower dose of cocaine (0.30 or
      0.18 mg/kg i.m.). The selective norepinephrine[fnc] uptake inhibitors talsupram,
      tomoxetine, nisoxetine and desipramine substituted for cocaine in the majority of
      subjects under the low-dose training condition, whereas the selective dopamine
      uptake inhibitor GBR 12909 [1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3
      phenylpropyl) piperazine] substituted for cocaine under both training conditions
      and the selective serotonin uptake inhibitor citalopram failed to substitute for
      cocaine under either condition. Representative alpha-1 [St 587 (2-(2-chloro-5
      trifluoromethyl-phenylimino)imidazolidine] and SDZ NVI 085 [(-)-(4aR, 10aR)
      3,4,4a,5,10,10a-hexahydro-6-methoxy-4- methyl-4-methyl-9-(methylthio)-2H
      naphth[2,3-b]-1,4-oxazine)], alpha-2 (clonidine and UK 14,304 (5-bromo-N-(4,5
      dihydro-1H-imidazol-2-yl)-6-quinoxalinamine]) and beta (clenbuterol) adrenoceptor
      agonists did not consistently substitute for cocaine under either condition in
      which they were studied. Pretreatment with the alpha-1 adrenoceptor blocker
      prazosin antagonized the DS effects of cocaine under both training conditions as
      well as the cocaine-like effects of talsupram and tomoxetine, but not GBR 12909,
      under the low-dose training condition. Pretreatment with the alpha-2 blocker
      efaroxan, the nonselective alpha blocker phentolamine and the beta blocker
      propranolol failed to alter the DS effects of cocaine consistently under either
      condition in which they were studied. Pretreatment with talsupram, at doses that
      did not substitute for cocaine when administered alone, enhanced the cocaine-like
      effects of GBR 12909 under both training conditions. The results support a role
      for norepinephrine uptake and alpha-1 adrenoceptor mechanisms in the DS effects
      of cocaine, possibly reflecting a facilitory noradrenergic influence on
      mesocorticolimbic dopamine activity.

PMID- 7562596
TI  - Characterization of the spinal antinociceptive activity of constrained
      peptidomimetic opioids.
AB  - We examined the in vitro and in vivo bioactivities of several families of
      peptidomimetic opioids including: constrained linear enkephalin (n = 12 analogs),
      dermorphin (n = 9 analogs) and morphiceptin (n = 17 analogs). The biological
      activities were assessed in vitro by examining the inhibitory effects of these
      agents on the electrically evoked contractions of the guinea pig ileum (GPI) and
      the mouse vas deferens (MVD) preparations. The in vivo bioactivities were
      determined from the antinociceptive activity of these agents on the 52.5 degrees
      C hot-plate test after spinal administration of rats with chronically placed
      spinal catheters. Examination of the effect of cyclization, incorporation of
      retro-inverso bonds and substitutions of D- or constrained amino acids reveals
      systematic changes in the activity of these agents. There was a significant
      correlation between the potency of these agents in the hot-plate bioassay and
      their activity in the GPI and, to a lesser extent, in the MVD tests. Examination
      of the ability of naltrindole (a delta selective antagonist) to reverse the drug
      action and the respective potency on the GPI and MVD, showed that a correlation
      exists with actions on the MVD, but not on the GPI, consistent with the
      likelihood that agents with high MVD/GPI ratios in vitro act at the mu sites,
      whereas those with low MVD/GPI ratios act at the delta receptor in the spinal
      cord. The close correlations between activity in the GPI and spinal cord suggest
      that the structural requirements for potency in the smooth muscle and in the
      spinal cord are essentially the same as those mu receptors that mediate
      nociceptive transmission.

PMID- 7562597
TI  - Characterization of nitric oxide generator-induced hippocampal [3H]norepinephrine
      release. I. The role of glutamate.
AB  - In this study we compared the effects of two nitrogen monoxide (NO) generators,
      hydroxylamine and S-nitroso-L-cysteine (NO-CYS), on hippocampal
      [3H]norepinephrine ([3H]NE) release. A 10-min incubation with hydroxylamine (3
      3,000 microM) or NO-CYS (30-10,000 microM) induced a concentration-dependent
      increase in the basal [3H]NE efflux with EC50 values of approximately 100 microM
      and 1 mM, respectively. Reduced hemoglobin, a NO scavenger, blocked both
      hydroxylamine- and NO-CYS-evoked [3H]NE release. Long-term exposure (> or = 25
      min) to 100 microM hydroxylamine, or to millimolar concentrations of NO-CYS,
      evoked a tetrodotoxin-insensitive [3H]NE release. However, a 10-min stimulation
      with either 100 microM hydroxylamine or 300 microM NO-CYS was sensitive to 0.5
      microM tetrodotoxin, a voltage-sensitive sodium channel blocker. This suggested
      that under these conditions hydroxylamine and NO-CYS induce [3H]NE release
      indirectly in part, perhaps via releasing an excitatory neurotransmitter. Indeed,
      kynurenate, a nonselective ionotropic glutamate receptor antagonist, produced an
      80% inhibition of the NO generator-evoked [3H]NE release. CGS 19755, a N-methyl-D
      aspartate receptor antagonist, had no significant effect, whereas the alpha-amino
      3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor antagonists, CNQX
      and GYKI 52446, inhibited the hydroxylamine response by 50%. In synaptosomes, a
      preparation in which synaptic interactions are nonsignificant, NO-CYS induced a
      dose-dependent release of both [3H]NE and [3H]glutamate. These data suggest that,
      in hippocampal slices, NO generators evoke [3H]NE release both directly from
      noradrenergic terminals and indirectly via releasing glutamate.

PMID- 7562598
TI  - Cepharanthin, a multidrug resistant modifier, is a substrate for P-glycoprotein.
AB  - P-glycoprotein modulators are respected to be multidrug resistance reversing
      agents in cancer chemotherapy. Some calcium channel blockers, calmodulin
      inhibitors or immunosuppressive agents have been used in clinical studies,
      although the dose of these drugs required to test in vitro experimental data
      might cause potent pharmacological effects which are not desirable in patients.
      By using LLC-GA5-COL150 cells that express P-glycoprotein specifically on the
      apical membranes, we examined the transport of anticancer drugs mediated by P
      glycoprotein. Cepharanthin, a biscoclaurine alkaloid, potently inhibits the
      transport of vinblastine and daunorubicin, both commonly used anticancer agents.
      The 50% inhibitory concentration of cepharanthin on daunorubicin transport was
      2.06 microM. Combined inhibitory effects on daunorubicin transport were observed
      when cepharanthin was used together with cyclosporin A, a potent
      immunosuppressive agent and P-glycoprotein modulator. Cepharanthin itself was
      transported by P-glycoprotein. Transcellular transport of cepharanthin across LLC
      GA5-COL150 cell monolayers was saturable when its concentration was under 5
      microM, and the transport was inhibited by P-glycoprotein modulators. These
      results indicate that cepharanthin can reverse multidrug resistance, and proper
      combination with other P-glycoprotein modulators could potentiate its inhibitory
      effect on expelling the anticancer drugs out of the cell via P-glycoprotein.

PMID- 7562599
TI  - Phenethyl isothiocyanate, a new dietary liver aldehyde dehydrogenase inhibitor.
AB  - Phenethyl isothiocyanate (PEITC) is found in cabbages and other commonly ingested
      cruciferous vegetables. Isothiocyanates have anticarcinogenic properties,
      proposed to be mediated in part by their inhibition of several cytochrome P450
      (CYP) forms. We administered PEITC to rats treated chronically with ethanol for
      38 days by means of total enteral nutrition model to inhibit CYP2E1. We observed
      that PEITC not only efficiently prevented the ethanol-induced elevation of CYP2E1
      apoprotein and mRNA, but also significantly elevated blood acetaldehyde levels.
      An elevation also was observed in naive animals acutely administered PEITC and
      ethanol, an effect found to be associated with marked inhibition of liver
      aldehyde dehydrogenase (ALDH). PEITC (1 mmol/kg) inhibited total liver ALDH
      activity by more than 70% and inhibition persisted for at least 24 hr. The
      inhibition was similar to that caused by an equimolar dose of disulfiram.
      Experiments using subcellular rat liver fractions revealed that both low- and
      high-Km ALDH forms were inhibited by low concentrations of PEITC (IC50 = 0.8-6.0
      microM). Importantly, the mitochondrial low-Km ALDH activity, which is mainly
      responsible for detoxification of low aldehyde levels, was strongly inhibited
      (IC50 = 1.4 microM). In contrast, neither alcohol dehydrogenase nor lactate
      dehydrogenase activity was inhibited by PEITC. Thus, PEITC inhibits liver ALDH
      with a potency similar to that of disulfiram, suggesting that, in susceptible
      individuals, ingestion of large amounts of cruciferous vegetables in combination
      with alcohol could give rise to antabus-like symptoms. This property of PEITC
      must be taken into account in experimental alcohol research and in evaluating its
      proposed anticarcinogenic actions on chemical procarcinogens that are activated
      into potentially carcinogenic aldehydes.

PMID- 7562600
TI  - Spinal opioid receptors and adenosine release: neurochemical and behavioral
      characterization of opioid subtypes.
AB  - Release of adenosine from the spinal cord contributes to spinal antinociception
      by morphine. Morphine induces a Ca(++)-dependent release of adenosine from dorsal
      spinal cord synaptosomes, which is augmented under partially depolarizing
      conditions. The present study examined the opioid receptor subtypes involved in
      this release, and determined whether adenosine is an important mediator of
      antinociception induced by the spinal administration of selective opioid agonists
      in rats. Nanomolar and micromolar concentrations of the selective mu opioid
      agonists DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin) and PLO17 ([N-MePhe3,D
      Pro4]morphiceptin) induced release of adenosine in a biphasic manner in the
      presence of a partial depolarization (addition of 6 mM K+ to the Krebs' medium).
      The delta opioid agonists DPDPE ([D-Pen2,D-Pen5]enkephalin) and DELT ([D
      Ala2,Cys4]deltorphin) and the kappa opioid agonist U50488H (trans-(+/-)-3,4
      dichloro-N-methyl-N-(2-(1-pyrroli-zemeacetamid e) had little effect on the
      release of adenosine except at high micromolar concentrations. Release of
      adenosine by mu (nanomolar) and delta (micromolar) ligands is Ca(++)-dependent,
      whereas the kappa (micromolar) receptor ligand releases adenosine via a Ca(++)
      independent mechanism. Behavioral antinociception using the hot-plate threshold
      test revealed that intrathecal administration of the mu and delta opioid receptor
      agonists produced dose-dependent antinociception with an order of potency of
      DAMGO, PLO17 > morphine, DELT > DPDPE. An ED75 dose of morphine, DAMGO or PLO17
      was attenuated dose-dependently by intrathecal pretreatment with the adenosine
      receptor antagonist caffeine. Caffeine did not block the antinociceptive response
      to delta agonists, but in fact augmented antinociception when combined with DPDPE
      and DELT. This augmentation was dose-dependent. This study demonstrates that
      activation of the mu receptor subtype is responsible for the opioid-induced
      release of adenosine from the spinal cord, that such release contributes to the
      spinal antinociception by mu agonists and that only release evoked by low doses
      of opioids is behaviorally relevant.

PMID- 7562601
TI  - Immunological characterization of urinary 8-epi-prostaglandin F2 alpha excretion
      in man.
AB  - F2-isoprostanes are prostaglandin (PG) F2-like compounds that are formed in vivo
      directly by free radical-catalyzed lipid peroxidation. One of the compounds that
      can be produced in abundance by such mechanism is 8-epi-PGF2 alpha, a potent
      vasoconstrictor. We have developed an enzyme immunoassay and a radioimmunoassay
      for measuring urinary concentrations of 8-epi-PGF2 alpha by raising antibodies
      against this compound. The antisera presented high titers (> 1/300,000) and
      provided highly sensitive assays (IC50, 8 and 24 pg/ml, for EIA and RIA,
      respectively); cross-reactivity with other PG was negligible. The interassay
      reproducibility of EIA was assessed by measuring the same urine stored frozen in
      aliquots after solid phase extraction and thin-layer chromatography (17%, n =
      13). Measurements of urinary 8-epi-PGF2 alpha by immunoassays were validated
      using different antisera and by comparison with gas chromatography/mass
      spectrometry. Healthy volunteers excreted 25 +/- 12 ng of 8-epi-PGF2 alpha/mmol
      creatinine (n = 19), with no circadian variation over three consecutive 8-hr
      collection periods (n = 10); preliminary results showed that excretion increased
      as a function of age. Urinary excretion of 8-epi-PGF2 alpha was unchanged by
      treatment with two nonsteroidal antiinflammatory drugs, Ibuprofen at 1.2 g/day
      for 4 days (n = 4) or aspirin as a single administration of 1 g (n = 6). In
      contrast, the urinary excretion of 11-dehydro-thromboxane B2, a platelet
      cyclooxygenase-derived metabolite was reduced by more than 80% after aspirin
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562602
TI  - Inactivation of the cardiac Na+ channels in guinea-pig ventricular cells through
      the open state.
AB  - 1. The inactivation kinetics of the Na+ current were investigated using the
      improved oil-gap voltage clamp method in single ventricular cells of guinea-pig
      hearts. 2. Activation of the Na+ current was observed on depolarization more
      positive than -50 mV from a holding potential of -100 mV, and inactivation was
      complete during these depolarizations. The time course of current decay was
      fitted by a double exponential at potentials between -40 and -15 mV, and
      virtually by a single exponential at more positive potentials. The decay time
      courses examined either by the double-pulse protocol or the single-pulse protocol
      were similar. 3. The double-pulse protocol clearly revealed a sigmoidal onset of
      inactivation on depolarization. The initial delay of inactivation decreased with
      more positive potentials. The time course of double-pulse inactivation was
      reconstructed by integrating the Na+ current recorded by a continuous
      depolarization. 4. These findings are consistent with the hypothesis that the
      cardiac Na+ channel inactivates exclusively through the open state.

PMID- 7562604
TI  - Coincidence of early glucose-induced depolarization with lowering of cytoplasmic
      Ca2+ in mouse pancreatic beta-cells.
AB  - 1. The temporal relationship between the early glucose-induced changes of
      membrane potential and cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in
      insulin-releasing pancreatic beta-cells. 2. The mean resting membrane potential
      and [Ca2+]i were about -70 mV and 60 nM, respectively, in 3 mM glucose. 3.
      Elevating the glucose concentration to 8-23 mM typically elicited a slow
      depolarization, which was paralleled by a lowering of [Ca2+]i. When the slow
      depolarization had reached a threshold of -55 to -40 mV, there was rapid further
      depolarization to a plateau with superimposed action potentials, and [Ca2+]i
      increased dramatically. 4. Imposing hyperpolarizations and depolarizations of 10
      mV from a holding potential of -70 mV had no detectable effect on [Ca2+]i.
      Furthermore, glucose elevation elicited a decrease in [Ca2+]i even at a holding
      potential of -70 mV. 5. Step depolarizations induced [Ca2+]i transients, which
      decayed with time courses well fitted by double exponentials. The slower
      component became faster by a factor of about 4 upon elevation of glucose,
      suggesting involvement of ATP-dependent Ca2+ sequestration or extrusion of
      [Ca2+]i. 6. Glucose stimulation increased the size and accelerated the recovery
      of carbachol-triggered [Ca2+]i transients, and thapsigargin, an intracellular
      Ca(2+)-ATPase inhibitor, counteracted the glucose-induced lowering of [Ca2+]i,
      indicating that calcium transport into intracellular stores is involved in
      glucose-induced lowering of [Ca2+]i. 7. The results support the notion that in
      beta-cells, nutrient-induced elevation of ATP leads initially to ATP-dependent
      removal of Ca2+ from the cytoplasm, paralleled by a slow depolarization due to
      inhibition of ATP-sensitive K+ channels. Only after depolarization has reached a
      threshold do action potentials occur, inducing a sharp elevation in [Ca2+]i.

PMID- 7562603
TI  - An ATP-sensitive potassium conductance in rabbit arterial endothelial cells.
AB  - 1. Whole-cell patch clamp recording was used to study an ATP-sensitive,
      sulphonylurea-inhibitable potassium (K+) conductance in freshly dissociated
      endothelial cells from rabbit arteries. 2. The ATP-sensitive K+ conductance was
      activated by micromolar concentrations of the K+ channel opener, levcromakalim,
      and by metabolic inhibition of endothelial cells using dinitrophenol and
      iodoacetic acid. The current-voltage (I-V) relationship obtained in isotonic K+
      solutions was linear between -150 and -50 mV and had a slope conductance of
      approximately 1 nS. 3. The permeability of the ATP-sensitive K+ conductance
      determined from reversal potential measurements exhibited the following ionic
      selectivity sequence: Rb+ > K+ > Cs+ >> Na+ > NH4+ > Li+. 4. Membrane currents
      activated by either levcromakalim or metabolic inhibition were inhibited by the
      sulphonylurea drugs, glibenclamide and tolbutamide, with half-maximal inhibitory
      concentrations of 43 nM and 224 microM and Hill coefficients of 1.1 and 1.2,
      respectively. Levcromakalim-induced currents were also inhibited by millimolar
      concentrations of Ba2+ or tetraethylammonium ions in the external solution. 5.
      Levcromakalim (3 microM) and metabolic inhibition hyperpolarized endothelial
      cells by approximately 10-15 mV in normal physiological salt solutions. The
      hyperpolarization induced by levcromakalim or metabolic inhibition was inhibited
      by bath application of 10 microM glibenclamide. 6. Internal perfusion of the
      cytosol of whole-cell voltage-clamped endothelial cells with an ATP-free pipette
      solution activated a membrane current which was reversibly inhibited by internal
      perfusion with a 3 mM MgATP pipette solution. This current was insensitive to
      other adenine and guanine nucleotides in the pipette solution. The inward current
      evoked in a nominally ATP-free internal solution was further increased by bath
      application of levcromakalim. 7. Levcromakalim (25 microM) did not induce a
      change in the intracellular Ca2+ concentration of fura-2-loaded endothelial
      cells, whereas metabolic inhibition caused a slow and sustained increase in
      intracellular Ca2+ concentration, which was attenuated by 10 microM glibenclamide
      applied externally.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562605
TI  - Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus
      oocytes.
AB  - 1. Voltage-dependent Ca2+ channels are multi-protein complexes composed of at
      least three subunits: alpha 1, alpha 2 delta and beta. Ba2+ currents were
      recorded in Xenopus oocytes expressing the neuronal alpha 1A Ca2+ channel, using
      the two-electrode voltage-clamp technique. Various subunit combinations were
      studied: alpha 1A, alpha 1A alpha 2 delta b, alpha 1A beta or alpha 1A alpha 2
      delta b beta. 2. The alpha 1A subunit alone directs the expression of functional
      Ca2+ channels. It carries all the properties of the channel: gating,
      permeability, voltage dependence of activation and inactivation, and
      pharmacology. The alpha 1A channel is activated by low voltages when
      physiological concentrations of the permeant cation are used. Both ancillary
      subunits alpha 2 delta and beta induced considerable changes in the biophysical
      properties of the alpha 1A current. The subunit specificity of the changes in
      current properties was analysed for all four beta gene products by coexpressing
      beta 1b, beta 2a, beta 3 and beta 4. 3. All beta subunits induce a stimulation in
      the current amplitude, a change in inactivation kinetics, and two hyperpolarizing
      shifts--one in the voltage dependence of activation and a second in the voltage
      dependence of steady-state inactivation. The most significant difference in
      regulation among beta subunits is the induction of variable rate constants of
      current inactivation. Rates of inactivation were induced in the following order
      (fastest to slowest): beta 3 > beta 1b = beta 4 > beta 2a. 4. The alpha 2 delta b
      subunit does not modify the properties of alpha 1A Ca2+ channels in the absence
      of beta subunits. However, this subunit increases the beta-induced stimulation in
      current amplitude and also regulates the beta-induced change in inactivation
      kinetics. 5. Of all the subunit combinations tested, Ca2+ channels that included
      a beta subunit were the most prone to decrease in activity. It is concluded that
      beta subunits are the primary target for the inhibitory mechanisms involved in
      Ca2+ channel run-down. 6. Both alpha 2 delta b and beta 1 b subunits slightly
      modified the sensitivity of the alpha 1A subunit to the snail peptide omega
      conotoxin MVIIC. 7. The subunit-induced changes in properties of the alpha 1A
      channel are surprisingly similar to changes reported for other alpha 1 subunits.
      These modifications in channel activity should therefore represent important
      functional landmarks in the on-going characterization of subunit-subunit
      interactions.

PMID- 7562606
TI  - Inhibition of N- and P-type calcium currents and the after-hyperpolarization in
      rat motoneurones by serotonin.
AB  - 1. We investigated the effects of serotonin (5-hydroxytryptamine, 5-HT) on whole
      cell barium currents through calcium channels in visualized neonatal rat
      hypoglossal motoneurones (HMs) in a thin brainstem slice preparation. 2. High
      voltage-activated (HVA) currents were elicited by depolarizing voltage steps from
      -70 to 0 mV; low voltage-activated (LVA) currents were evoked using steps to
      between -30 and -40 mV from hyperpolarized potentials (< -80 mV). 5-HT (1.0
      microM) inhibited HVA currents by at least 10% in 70% of HMs tested (n = 99); in
      those responsive neurones, 5-HT decreased HVA current by 22 +/- 1.3% (mean +/-
      S.E.M.). In contrast, 5-HT had no effect on LVA current amplitude in HMs (n = 7).
      3. Calcium current inhibition was mimicked by 5-carboxamidotryptamine maleate (5
      CT), a 5-HT1 receptor agonist, and by R(+)-8-hydroxydipropylaminotetralin
      hydrobromide (8-OH-DPAT), a specific 5-HT1A agonist; N-(3-trifluoromethylphenyl)
      piperazine hydrochloride (TFMPP), a 5-HT1B agonist, was without effect. The
      effect of 5-HT was blocked by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4-[4-(2
      phthalimido)butyl]piperazine hydrobromide (NAN-190) but not by ketanserin, a 5
      HT2A/2C antagonist. Although R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      hydrochloride (DOI), a 5-HT2A/2C agonist, mimicked the current inhibition by 5
      HT, it was ineffective in the presence of NAN-190. These data indicate that 5
      HT1A receptors mediate calcium current inhibition by 5-HT. 4. Following
      application of either omega-conotoxin-GVIA (omega-CgTX) or omega-agatoxin-IVA
      (omega-Aga-IVA), to block N- and P-type components of calcium current, the 5-HT
      sensitive current was reduced; 5-HT had no effect on the current remaining after
      application of both toxins. Thus, 5-HT inhibits both N- and P-type calcium
      currents in neonatal HMs. 5. Inhibition of HVA current by 5-HT was irreversible,
      and subsequent applications of 5-HT were occluded, when GTP gamma S was
      substituted for GTP in the pipette. In addition, inhibition of HVA current by 5
      HT was relieved following depolarizing prepulses. These data indicate that
      inhibition of calcium channels by 5-HT is mediated by G proteins. 6. Under
      current clamp, both 5-HT and 8-OH-DPAT decreased the amplitude of the after
      hyperpolarization (AHP) that followed action potentials, indicating involvement
      of a 5-HT1A receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562607
TI  - GABAB receptor-mediated presynaptic inhibition in guinea-pig hippocampus is
      caused by reduction of presynaptic Ca2+ influx.
AB  - 1. The hypothesis that activation of GABAB receptors inhibits evoked synaptic
      transmission by reducing the presynaptic Ca2+ influx was tested using a recently
      developed technique for simultaneously recording the presynaptic Ca2+ transient
      ([Ca2+]t) and the field excitatory postsynaptic potential (fEPSP) evoked by a
      single electrical stimulus at CA3 to CA1 synapses of guinea-pig hippocampus. 2.
      The GABAB receptor agonist baclofen reversibly blocked, in a dose-dependant
      manner, both the fEPSP and the presynaptic [Ca2+]t with similar time courses.
      During application of baclofen, the fEPSP was proportional to about the fourth
      power of the presynaptic [Ca2+]t, and the presynaptic fibre volley and the
      resting Ca2+ level did not change. These results are similar to those we
      previously observed following application of several voltage-dependent Ca2+
      channel blockers, suggesting that baclofen inhibits the fEPSP by blocking the
      presynaptic Ca2+ influx. 3. The inhibition by baclofen of both the fEPSP and the
      presynaptic [Ca2+]t was blocked by the GABAB receptor antagonist CGP 35348,
      consistent with the causal relationship between the GABAB receptor-mediated
      presynaptic inhibition of the [Ca2+]t and the fEPSP. 4. The inhibition by
      baclofen of the [Ca2+]t was partially occluded by application of the voltage
      dependent Ca2+ channel blocker omega-conotoxin-GVIA (omega-CgTX-GVIA), but not
      omega-agatoxin-IVA (omega-AgaTX-IVA), suggesting that baclofen reduces the
      presynaptic [Ca2+]t by blocking Ca2+ channels including the omega-CgTX-GVIA
      sensitive type. 5. We conclude that baclofen inhibits evoked transmitter release
      by reducing presynaptic Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562609
TI  - Characterization of a volume-sensitive chloride current in rat osteoblast-like
      (ROS 17/2.8) cells.
AB  - 1. During osmotic swelling, cultured osteoblastic cells (ROS 17/2.8) exhibited
      activation of large amplitude Cl- currents in the whole-cell configuration of the
      patch-clamp technique. Effects of hypotonic shock on cell volume and membrane
      conductance were rapidly reversed on return to isotonic conditions. 2. Voltage
      command pulses in the range -80 to +50 mV produce instantaneous activation of Cl-
      currents. At potentials more positive than +50 mV the current exhibited time
      dependent inactivation. The instantaneous current-voltage relationship was
      outwardly rectifying. 3. The anion permeability sequence of the induced current
      was SCN- (2.2) > i- (1.9) > Br- (1.5) > Cl- (1.0) > F- (0.8) > gluconate- (0.2).
      This corresponds to Eisenman's sequence I. 4. The volume-sensitive Cl- current
      was effectively inhibited by the Cl- channel blockers 4,4'-
      diisothiocyanatostilbene-2,2-disulphonic acid (DIDS) and 5-nitro-2-(3
      phenylpropylamino) benzoic acid (NPPB). Outward currents were more effectively
      suppressed by DIDS than inward currents. The concentrations for 50% inhibition
      (IC50) of outward and inward currents were 81 and 298 microM, respectively. NPPB
      was equally effective at inhibiting outward and inward currents (IC50 of 64
      microM). The current was relatively insensitive to diphenylamine-2-carboxylate
      (DPC), 500 microM producing only 22.5 +/- 4.0% inhibition. 5. Inhibitors of
      protein kinase A (H-89, 1 microM) and tyrosine kinase (tyrphostin A25, 200
      microM) were without effect upon activation of Cl- currents in response to
      hypotonic shock. Under isotonic conditions, elevation of intracellular Ca2+ by
      ionomycin (1 microM) or activation of protein kinase C by 12-O
      tetradecanoylphorbol 13-acetate (TPA, 0.1 microM) failed to evoke increases in
      basal Cl- conductance levels. 6. It is concluded that an outwardly rectifying Cl-
      conductance is activated upon osmotic swelling and may be involved in cell volume
      regulation of ROS 17/2.8 cells.

PMID- 7562608
TI  - Effects of high-energy phosphates on carbachol-evoked cationic current in single
      smooth muscle cells from guinea-pig ileum.
AB  - 1. Single smooth muscle cells from the longitudinal muscle layer of guinea-pig
      small intestine were voltage clamped in the whole-cell recording mode with patch
      pipettes. The cationic current (Icat) evoked by application of 50 microM
      carbachol (CCh) was examined when free internal calcium in the cell was 'clamped'
      at 10(-7) M with 20 mM BAPTA. The effects of varying the composition of the
      pipette solution were studied. 2. Phosphocreatine (PCr, 6 mM) added to the
      pipette solution increased Icat by about 7-fold (to near 620 pA); lower
      concentrations had similar, generally lesser, effects. Na2ATP (3 or 6 mM) with or
      without 5 mM MgCl2 was much less effective than phosphocreatine alone. Addition
      of 3 mM Na2ATP reduced Icat, whether or not phosphocreatine was present. 3.
      Creatine (6 mM) with or without 2 mM Na2ATP was less effective than
      phosphocreatine in maintaining Icat. 4. GTP (0.1 mM) did not affect Icat evoked
      by CCh, whether phosphocreatine was present or not. 5. GTP gamma S (0.2 mM)
      included in pipette solution mimicked the effect of CCH and evoked Icat
      independently of whether PCr was present or not in the pipette solution.
      Including 5 mM ATP in the pipette reduced this current, whereas 5'-adenylyl
      imidodiphosphate (AMP-PNP) and ADP were without effect. 6. The results show that
      phosphocreatine increases membrane channel responsiveness to receptor activation
      and that ATP above 2 mM suppresses it.

PMID- 7562610
TI  - The non-specific ion channel in Torpedo ocellata fused synaptic vesicles.
AB  - 1. Synaptic vesicles were isolated and fused into large structures with a
      diameter of more than 20 microns to characterize their ionic channels. The 'cell'
      attached and inside-out configurations of the patch clamp technique were used. 2.
      Two types of ion channels were most frequently observed: a low conductance
      chloride channel and a high conductance non-specific channel. 3. The non-specific
      channel has a main conducting state and a substate. The main conducting state has
      a slope conductance of 246 +/- 15 pS (+/- S.E.M., n = 15), in the presence of
      different combinations of KCl and potassium glutamate. 4. From the reversal
      potentials of the current-voltage (I-V) relation, it was concluded that this
      channel conducts both Cl- and K+. 5. The non-specific channel is highly voltage
      dependent: under steady-state voltages it has a high open probability near 0 mV
      and does not inactivate; when the membrane is hyperpolarized (pipette side more
      positive), the open probability decreases dramatically. 6. Voltage pulses showed
      that upon hyperpolarization (from holding potentials between -20 and + 20 mV),
      the channels deactivated; when the membrane was stepped back to the holding
      potential, the channels reactivated rapidly. 7. In a number of experiments, when
      the pipette side was made more negative than the bath, the open probability also
      decreased. 8. Frequently, a substate with a conductance of about 44 +/- 4% (+/-
      S.E.M., n = 3) of the main state was detected. 9. We speculate that this non
      specific ion channel may have different roles at the various stages of the life
      cycle of the synaptic vesicle. When the synaptic vesicle is an intracellular
      structure, it might help its transmitter-concentrating capacity by dissipating
      the polarization. After fusion with the surface membrane, it might constitute an
      additional conductance pathway, taking part in frequency modulation of synaptic
      transmission.

PMID- 7562611
TI  - Spontaneous, ligand-independent activity of the cGMP-gated ion channels in cone
      photoreceptors of fish.
AB  - 1. We studied the electrical conductance of membrane patches detached from the
      outer segment of single cone photoreceptors isolated from striped bass retina. 2.
      Only a single class of ion channels exists in the plasma membrane of the cone
      outer segments; they are gated by cytoplasmic cGMP and select cations over
      anions, but distinguish poorly among cations. In the absence of added cGMP and of
      divalent cations, however, membrane patches detached from the outer segments
      exhibit a small conductance that ideally selects cations over anions, but
      distinguishes poorly between Na+ and Li+. 3. The cGMP-independent conductance
      does not arise from the effect of residual cGMP that may remain associated with
      the detached membrane, because treatment of the patch with cGMP-specific
      phosphodiesterase does not affect this conductance. 4. The cGMP-independent
      conductance is pharmacologically indistinguishable from that activated by cGMP.
      Ca2+ and L-cis-diltiazem block both conductances at comparable concentrations and
      with similar quantitative characteristics. 5. We analysed the noise of Ca(2+)- or
      L-cis-diltiazem-dependent macroscopic currents both in the presence and in the
      absence of cGMP. In the presence of cGMP, the power density spectrum of the noise
      is well fitted by the sum of two Lorentzian components. The same function with
      similar corner frequencies fits the noise of the cGMP-independent currents.
      However, the total power in the current fluctuations is smaller in the absence of
      cGMP than in its presence; also, the ratio of the zero frequency asymptotes of
      the low over the high frequency components, S1(0)/Sh(0), is larger in the absence
      of cGMP than in its presence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562613
TI  - Action of salicylate on membrane capacitance of outer hair cells from the guinea
      pig cochlea.
AB  - 1. The effect of salicylate on membrane capacitance and intracellular pH has been
      measured in isolated outer hair cells (OHCs) during whole cell recording. Cell
      membrane capacitance was measured using a lock-in amplifier technique. 2.
      Salicylate applied in the bath reduced the fast charge movement, equivalent to a
      voltage-dependent membrane capacitance, present in OHCs. Simultaneous measurement
      of membrane capacitance and voltage-driven cell length changes showed that
      salicylate reduced both together. 3. A small effect of salicylate on outward
      currents at 0 mV was observed. Sodium salicylate (5 mM) reduced the currents by
      19% and another weak acid, sodium butyrate (10 mM), reduced outward currents in
      OHCs by 15%. 4. The ratiometric dye 2,7-bis(2-carboxymethyl)-5,6
      carboxyfluorescein (BCECF) was used to measure pHi changes in OHCs during weak
      acid exposure. Membrane capacitance and pHi were measured simultaneously in OHCs
      exposed first to 10 mM sodium butyrate and then to 5 mM sodium salicylate.
      Although both compounds produced a similar reduction in pHi, butyrate decreased
      the resting capacitance from a mean resting capacitance of 35 pF (at -30 mV) by
      5.4 +/- 2.1 pF, whereas salicylate decreased it by 15.7 +/- 2.3 pF (n = 4). 5.
      Exposure of OHCs to 10 mM sodium benzoate, an amphiphilic anion, reduced resting
      membrane capacitance at -30 mV by 9.2 +/- 3.2 pF (n = 3). Outward currents,
      measured at 0 mV, were reduced by 0.25 +/- 0.05 nA during benzoate application,
      comparable with the effect of salicylate. 6. Capacitance was measured during slow
      bath application of salicylate. The resulting dose-capacitance curve had a Hill
      coefficient of 3.40 +/- 0.85 (n = 4) and a half-maximal dose of 3.95 +/- 0.34 mM.
      The dose-capacitance curve was not significantly voltage dependent. 7. Salicylate
      had no detectable effect on the resting capacitance of Deiters' cells, a non
      sensory cell type of the organ of Corti. 8. It is concluded that many of the
      described effects of salicylate on hearing may arise from the partitioning of the
      salicylate molecule into the membrane of the OHC and consequent inhibition of OHC
      motility.

PMID- 7562612
TI  - Temporal structure in the light response of relay cells in the dorsal lateral
      geniculate nucleus of the cat.
AB  - 1. The spike interval pattern during the light responses of 155 on- and 81 off
      centre cells of the dorsal lateral geniculate nucleus (LGN) was studied in
      anaesthetized and paralysed cats by the use of a novel analysis. Temporally
      localized interval distributions were computed from a 100 ms time window, which
      was shifted along the time axis in 10 ms steps, resulting in a 90% overlap
      between two adjacent windows. For each step the interval distribution was
      computed inside the time window with 1 ms resolution, and plotted as a greyscale
      coded pixel line orthogonal to the time axis. For visual stimulation, light or
      dark spots of different size and contrast were presented with different
      background illumination levels. 2. Two characteristic interval patterns were
      observed during the sustained response component of the cells. Mainly on-cells
      (77%) responded with multimodal interval distributions, resulting in elongated
      'bands' in the 2-dimensional time window plots. In similar situations, the
      interval distributions for most (71%) off-cells were rather wide and featureless.
      In those cases where interval bands (i.e. multimodal interval distributions) were
      observed for off-cells (14%), they were always much wider than for the on-cells.
      This difference between the on- and off-cell population was independent of the
      background illumination and the contrast of the stimulus. Y on-cells also tended
      to produce wider interval bands than X on-cells. 3. For most stimulation
      situations the first interval band was centred around 6-9 ms, which has been
      called the fundamental interval; higher order bands are multiples thereof. The
      fundamental interval shifted towards larger sizes with decreasing stimulus
      contrast. Increasing stimulus size, on the other hand, resulted in a
      redistribution of the intervals into higher order bands, while at the same time
      the location of the fundamental interval remained largely unaffected. This was
      interpreted as an effect of the increasing surround inhibition at the geniculate
      level, by which individual retinal EPSPs were cancelled. A changing level of
      adaptation can result in a mixed shift/redistribution effect because of the
      changing stimulus contrast and changing level of tonic inhibition. 4. The
      occurrence of interval bands is not directly related to the shape of the
      autocorrelation function, which can be flat, weakly oscillatory or strongly
      oscillatory, regardless of the interval band pattern. 5. A simple computer model
      was devised to account for the observed cell behaviour. The model is highly
      robust against parameter variations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562614
TI  - Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli:
      estimates of receptor depth and threshold.
AB  - 1. Responses to ramped or stepped temperature stimuli were obtained from fifty
      three cutaneous C fibre mechano-heat nociceptors (CMHs) in the hairy skin of the
      pentobarbitone-morphine anaesthetized monkey. A three-layer heat transfer model
      was developed to describe the temperature distribution within the skin and to
      estimate receptor depth and heat threshold. 2. Surface heat threshold, defined as
      the surface temperature when the first action potential occurs, increased as: (a)
      the rate of temperature rise for the ramped stimuli increased from 0.095 to 5.8
      degrees C s-1; (b) the duration of stepped heat stimuli decreased from 30 to 1 s;
      and (c) the base temperature of stepped heat stimuli decreased from 38 to 35
      degrees C. These results suggest that the heat threshold for CMHs is determined
      by the temperature at the depth of the receptor. 3. Receptor depth estimates from
      responses to ramped stimuli ranged from 20 to 570 microns with a mean of 201
      microns. The estimated mean receptor heat threshold was 40.4 +/- 2.2 degrees C
      (+/- S.D.). No correlation was observed between depth and thermal or mechanical
      threshold. The average receptor depth and threshold, estimated from the responses
      to stepped heat stimuli, were 150 microns and 40.2 degrees C, respectively. 4. We
      conclude that: (a) the receptor endings of CMHs occur in the epidermis and
      dermis; (b) temperature at the level of the receptor determines threshold; (c)
      temperature at the receptor ending is much lower than skin surface temperature at
      threshold; and (d) the tight distribution of receptor heat thresholds suggests a
      uniform transducer mechanism for heat in CMHs.

PMID- 7562615
TI  - Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli:
      correlation with pain threshold in humans.
AB  - 1. Ramped heat stimuli were used to compare the effects of rate of temperature
      change on the responses of monkey nociceptors and on heat pain threshold in human
      subjects. Recordings were made from twenty-five cutaneous C fibre mechano-heat
      nociceptors (CMHs) innervating the hairy skin in the anaesthetized monkey. Heat
      pain thresholds were determined on the volar forearm of eight human subjects
      using a converging staircase technique. 2. The heat pain threshold decreased as
      stimulus ramp rate increased. In contrast, the CMH heat threshold, defined as the
      surface temperature at which the first action potential occurred, increased as
      stimulus ramp rate increased. Thus, the properties of the heat stimulus that
      dictate heat pain threshold are different from the properties of the heat
      stimulus that govern the initiation of a response in nociceptors. 3. Peak
      discharge frequency of CMHs during the heat ramp increased with stimulus ramp
      rate. Heat pain threshold was correlated with achievement of a minimum discharge
      rate in nociceptors (0.5 Hz), rather than with the threshold for action potential
      initiation.

PMID- 7562616
TI  - Tyrosine phosphorylation during synapse formation between identified leech
      neurons.
AB  - 1. We have examined whether tyrosine phosphorylation is required for synapse
      formation between identified neurons from the central nervous system of the leech
      in culture. 2. Within a few hours of contact with the cell body of the
      serotonergic Retzius neuron (R cell), the soma of the postsynaptic pressure
      sensitive neuron (P cell), but not the R cell, could be labelled intracellularly
      with an antibody against phosphotyrosine residues. The labelling seemed specific
      for P cells contacted by R cells, as it was greatly reduced in pairs of either R
      or P cells and in single cells. Genistein (20 microM) and lavendustin A (10
      microM), selective inhibitors of tyrosine kinases, blocked the labelling of
      contacted P cells, whereas their ineffective analogues (genistein and lavendustin
      B) had no effect on labelling. 3. R cell contact also induced the loss of an
      extrasynaptic, depolarizing response (due to modulation of cation channels) to
      serotonin (5-HT) in the P cell within a few days of juxtaposing cell bodies and
      within an hour of contact with growth cones. Treatment of the neurons with the
      tyrosine kinase inhibitors (but not the ineffective analogues) prevented the loss
      of the depolarizing response and of single cation channel modulation by 5-HT. 4.
      R cells formed inhibitory, Cl(-)-dependent synapses with P cells. Synapse
      formation was prevented by the tyrosine kinase inhibitors but not by their
      ineffective analogues. These compounds had no obvious effect on neurite outgrowth
      or cell adhesion. We conclude that tyrosine phosphorylation is a signal during
      the formation of this synapse.

PMID- 7562617
TI  - Tachykininergic slow depolarization of motoneurones evoked by descending fibres
      in the neonatal rat spinal cord.
AB  - 1. In the isolated spinal cord of the neonatal rat, repetitive electrical
      stimulation of the upper cervical region elicited a prolonged depolarization of
      lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly
      from ventral roots, or intracellularly. 2. This depolarizing response was
      markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2
      amino-5-phosphonovaleric acid (D-APV, 30 microM) and 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5
      hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 3. In the
      presence of these antagonists, a small part of the depolarizing response of slow
      time course remained, and this response was partially blocked by the tachykinin
      NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In
      contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no
      effect on the depolarizing response. 4. The slow depolarizing response in the
      presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase
      inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow
      depolarization became smaller after prolonged treatment (5-7 h) with 5,7
      dihydroxytryptamine (10 microM), a neurotoxin for 5-HT neurones. Under such
      conditions, the effects of thiorphan and GR71251 on the slow depolarization were
      virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications
      of tachykinins, substance P and neurokinin A produced depolarizing responses of
      lumbar motoneurones, and the responses were depressed by GR71251 and potentiated
      by thiorphan. 7. These results suggest that tachykinins contained in serotonergic
      fibres serve as neurotransmitters mediating the descending fibre-evoked slow
      excitatory postsynaptic potentials in motoneurones.

PMID- 7562618
TI  - In vivo activity of B- and C-neurones in the paravertebral sympathetic ganglia of
      the bullfrog.
AB  - 1. Spontaneous, in vivo synaptic activity was recorded from 146 B-cells and 60 C
      cells in the IXth and Xth paravertebral sympathetic ganglia of the urethane
      anaesthetized bullfrog. Sympathetic outflow to the blood vessels, which are
      innervated by C-cells, is different from that received by targets in the skin,
      which are innervated by B-cells. 2. B-cells were divided into three groups: the
      first (61 cells) exhibited only action potentials (APs) at 0.01-0.3 s-1; the
      second (59 cells) exhibited APs and EPSPs and the third (26 cells) were silent.
      In addition to their usual suprathreshold input from the ipsilateral sympathetic
      chain, 53% of B-cells received subthreshold input which probably arose from
      fibres in the contralateral chain. 'Slow' B-cells exhibited less subthreshold
      activity and a slightly higher AP frequency than 'fast' B-cells. All B-cells are
      involved in a sympathetic reflex which is activated by tactile stimulation of the
      skin of the hindlimb. Activation of this reflex increased AP frequency without
      promoting long-lasting depolarization. 3. Sixty-seven per cent of C-cells
      exhibited rhythmic bursting activity with or without small intraburst EPSPs.
      Bursts tended to correlate with electrocardiographic (ECG) activity. The
      remainder exhibited an irregular pattern of activity which was not correlated
      with ECG activity and which included one to three APs and EPSPs interspersed
      between the bursts. Activity of both types of C-cell was inhibited following
      stimulation of the skin. 4. An average of twenty-three B-cells and twenty-one C
      cells discharge simultaneously in vivo. This reflects branching of preganglionic
      fibres and results in synchrony of discharge in both postganglionic B- and C
      fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562619
TI  - Local modulation of adrenergic responses in the hindlimb vasculature of the
      intact conscious rat.
AB  - 1. Local modulation of adrenergic responses was examined in the hindlimb
      vasculature of chronically instrumented intact conscious rats. Sprague-Dawley
      rats (n = 22) were instrumented with a Doppler flow probe around the right common
      iliac artery, a polyethylene catheter inserted just distal to the flow probe and
      a left carotid arterial catheter. 2. The effects of various concentrations of the
      alpha 1-adrenergic receptor agonist phenylephrine (0.005-0.075 microgram kg-1),
      the alpha 2-adrenergic receptor agonist clonidine (0.1-0.7 microgram kg-1), and
      the endogenous adrenergic receptor agonist adrenaline (0.02-0.08 microgram kg-1),
      were investigated under control conditions, and in the presence of the nitric
      oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester hydrochoride
      (L-NAME) (NO-X, 0.2 mg kg-1) and the cyclo-oxygenase inhibitor indomethacin (CO
      X, 10 mg kg-1). Results were presented as dose-response curves. 3. Heart rate and
      arterial pressure were not altered by any of the agents because all were locally
      injected into the hindlimb vasculature and the selected doses were lower than
      those which elicited systemic responses. 4. Maximal vasoconstrictor responses to
      phenylephrine were enhanced in the presence of NO-X (50 +/- 6%) and CO-X (70 +/-
      9%). Maximal vasoconstrictor responses to clonidine were also enhanced in the
      presence of NO-X (75.3 +/- 4.8%) and CO-X (50.6 +/- 5.7%). 5. The responses to
      adrenaline were biphasic; NO-X significantly attenuated the vasodilator response
      (87 +/- 6%), and enhanced the vasoconstrictor response (51 +/- 7%). CO-X
      attenuated the vasoconstrictor response (71 +/- 6%). 6. These results demonstrate
      local modulation of responses to alpha 1- and beta-adrenergic receptor agonists
      by receptor-mediated dose-dependent release of NO and prostaglandins.

PMID- 7562620
TI  - Modulation of renal medullary ionic hypertonicity by prostaglandins: data from
      tissue admittance studies in the rat.
AB  - 1. Modulation of the cortico-papillary electrolyte gradient by prostaglandins
      (PG) was studied in the kidney of anaesthetized rats. The intrarenal PG activity
      was varied by synthesis blockade with indomethacin (Ind) or meclophenamate (Me)
      and by intrarenal infusion of prostaglandin E2 (PGE2). 2. The interstitial
      electrolyte concentration in the medulla was continuously recorded in the kidney
      in situ as tissue electrical admittance (reciprocal impedance); the total renal
      blood flow (RBF), inulin clearance (Cin) and renal excretion were measured
      simultaneously. 3. Indomethacin and Me (15 mg kg-1 h-1) increased tissue
      admittance 15-20% in the inner and 12-15% in the outer medulla (P < 0.001)
      whereas PGE2 (300 ng kg-1 min-1) decreased admittance 14 and 8%, respectively (P
      < 0.01). 4. Renal blood flow and Cin were not affected by intrarenal PG activity
      changes. There was an increase in urine concentration after PG blockade and a
      delayed decrease after PGE2 infusion. 5. A joint analysis of the dynamics of
      medullary tissue admittance, renal haemodynamics and renal excretion provides
      evidence that PGs modify the medullary ionic hypertonicity by affecting NaCl
      transport in the ascending limb of the loop of Henle.

PMID- 7562622
TI  - Opioid depression of respiration in neonatal rats.
AB  - 1. The effects of opioid receptor agonists and antagonists on the breathing
      pattern of neonatal rats were studied. Three experimental approaches were taken.
      In the first approach, the effects of opioid agonists and antagonists on the
      spontaneous respiratory neural activity generated by brainstem-spinal cords
      isolated from neonatal rats aged 0-4 days postnatal (P0-4) maintained in vitro
      were studied. Secondly, similar studies were performed utilizing medullary slice
      preparations consisting of respiratory rhythm-generating regions (pre-Botzinger
      complex). Thirdly, whole-body plethysmographic recordings were obtained from
      unanaesthetized neonatal (P0-18) rats before and after I.P. administration of
      opioid-receptor agonists and antagonists. 2. The mu-receptor agonists
      morphiceptin and DAGO (Tyr-D-Ala-Gly-[NMePhe]-Gly-ol), when added either to the
      solutions bathing the brainstems of neonatal rat brainstem-spinal cord
      preparations or bathing the medullary slice preparations, resulted in a naloxone
      reversible, dose-dependent decrease in the frequency of respiratory rhythmic
      discharge. 3. The respiratory burst frequency and amplitude in vitro were
      unaffected by the addition of the delta-opioid receptor agonist DPDPE ([D-pen2,5]
      enkephalin) and the kappa-opioid receptor agonist U50488 (trans-[+]-3,4-dichloro
      N-methyl-N-(2-[1- pyrrolidinyl]cyclohexyl) benzene-acetamide) or the opioid
      receptor antagonist naloxone. 4. Intraperitoneal administration of the mu-opioid
      receptor agonist fentanyl resulted in a naloxone-reversible, dose-dependent
      decrease in the frequency and amplitude of breathing of unanaesthetized neonatal
      rats (P0-P10). I.P. administration of the delta-opioid receptor agonist DPDPE did
      not affect breathing of neonatal rats until the second week postnatally. 5. We
      conclude that opioids suppress the frequency of neonatal rat respiration by
      acting via mu-opioid receptors located within regions of the ventral medulla
      containing respiratory rhythm-generating centres (the pre-Botzinger complex).
      delta-Opioid receptor activation does not affect breathing in neonatal rats until
      approximately the second week postnatally.

PMID- 7562621
TI  - Extracellular volume and blood volume in chronically catheterized fetal sheep.
AB  - 1. To determine the extracellular volume (ECV) in fetal sheep and its
      distribution between the plasma and interstitial spaces, ECV, blood volume (BV)
      and haematocrit were measured in ten chronically catheterized fetal sheep aged
      121-133 days. Relationships with age, weight and other fetal variables, including
      glomerular filtration rate (GFR), were studied. 2. ECV was measured as the mean
      of the volumes of distribution of [3H]inulin and [14C]mannitol extrapolated to
      time zero. The time zero volume of distribution was 1506 +/- 79 ml (means +/-
      S.E.M.) for inulin and 1590 +/- 80 ml for mannitol. The ECV was 1548 +/- 79 ml
      (632 +/- 18 ml (kg fetal wt)-1). BV, measured using 51Cr-labelled red cells, was
      351 +/- 27 ml (141 +/- 6 ml kg-1). Haematocrit, plasma volume and interstitial
      volume were 34 +/- 1%, 229 +/- 17 ml (92 +/- 3 ml kg-1) and 1319 +/- 63 ml (540
      +/- 17 ml kg-1), respectively. 3. Interstitial volume per kilogram fell with
      increasing fetal weight (P = 0.026). BV per kilogram did not change with weight
      or age. 4. The plasma: interstitial volume ratio was 0.17 +/- 0.01. This ratio
      increased as fetal weight and age increased (P = 0.026 and P = 0.044), that is,
      the proportion of ECV that was contained outside the vascular compartment was
      lower in heavier or older fetuses. 5. Since GFR was 3.4 +/- 0.4 ml min-1, the
      entire fetal ECV was filtered by the fetal kidney only 3.1 +/- 0.3 times per day.

PMID- 7562623
TI  - Effect of vibration on antagonist muscle coactivation during progressive fatigue
      in humans.
AB  - 1. Biceps femoris antagonist coactivation increases during progressive fatigue.
      Our purpose was to determine if the mechanism that increases coactivation during
      fatigue is susceptible to vibration. Vibration drives alpha-motoneurons via the
      Ia loop, producing force without descending motor drive, and thus uncoupling
      antagonist and agonist activation. Evidence that vibration increases coactivation
      disproportionately from its 'common drive' would suggest the possibility that
      some of the effects of fatigue are mediated through a segmental reflex loop. 2.
      Ten male subjects performed repeated maximal voluntary isometric contractions
      (MVCs) of the knee extensors of one leg. Paired submaximal test contractions (50%
      of MVC), without visual feedback, were performed when MVC reached 85, 70 and then
      50% of its initial value. Vibration was applied to the patellar tendon during one
      test contraction in each pair. 3. Vibration reduced test contraction force below
      control values. However, coactivation increased at the same rate in both
      conditions. Biceps femoris coactivation was greater during vibration, but did not
      change during fatigue in either condition. 4. Our observations suggest that
      agonist-antagonist muscle pairs are controlled as a single motor unit pool by a
      common central drive. Vibrating the agonist increases antagonist coactivity, but
      does not alter the rate at which coactivation increases during fatigue. This
      supports the idea that agonist coactivation is controlled by a central mechanism.

PMID- 7562624
TI  - Reduced servo-control of fatigued human finger extensor and flexor muscles.
AB  - 1. In healthy human subjects holding the index finger semi-extended at the
      metacarpophalangeal joint against a moderate load, electromyographic (EMG)
      activity was recorded from the finger extensor and flexor muscles during
      different stages of muscle fatigue. The aim was to study the effect of muscle
      fatigue on the level of background EMG activity and on the reflex responses to
      torque pulses causing sudden extensor unloadings. Paired comparisons were made
      between the averaged EMG and finger deflection responses under two conditions:
      (1) at a stage of fatigue (following a sustained co-contraction) when great
      effort was required to maintain the finger position, and (2) under non-fatigue
      conditions while the subject tried to produce similar background EMG levels to
      those in the corresponding fatigue trials. 2. Both the unloading reflex in the
      extensor and the concurrent stretch reflex in the flexor were significantly less
      pronounced and had a longer latency in the fatigue trials. Consequently, the
      finger deflections had a larger amplitude and were arrested later in the fatigue
      trials. 3. It is concluded that--with avoidance of 'automatic gain compensation',
      i.e. reflex modifications attributable to differences in background EMG levels-
      the servo-like action of the unloading and stretch reflexes is reduced in
      fatigued finger extensor and flexor muscles.

PMID- 7562625
TI  - Mitochondrial membrane potential in single living adult rat cardiac myocytes
      exposed to anoxia or metabolic inhibition.
AB  - 1. The relation between mitochondrial membrane potential (delta psi m) and cell
      function was investigated in single adult rat cardiac myocytes during anoxia and
      reoxygenation. delta psi m was studied by loading myocytes with JC-1 (5,5',6,6'
      tetrachloro-1,1',3,3'- tetra-ethylbenzimidazolylcarbocyanine iodide), a
      fluorescent probe characterized by two emission peaks (539 and 597 nm with
      excitation at 490 nm) corresponding to monomer and aggregate forms of the dye. 2.
      De-energizing conditions applied to mitochondria, cell suspensions or single
      cells decreased the aggregate emission and increased the monomer emission. This
      latter result cannot be explained by changes of JC-1 concentration in the aqueous
      mitochondrial matrix phase indicating that hydrophobic interaction of the probe
      with membranes has to be taken into account to explain JC-1 fluorescence
      properties in isolated mitochondria or intact cells. 3. A different sensitivity
      of the two JC-1 forms to delta psi m changes was shown in isolated mitochondria
      by the effects of ADP and FCCP and the calibration with K+ diffusion potentials.
      The monomer emission was responsive to values of delta psi m below 140 mV, which
      hardly modified the aggregate emission. Thus JC-1 represents a unique double
      sensor which can provide semi-quantitative information in both low and high
      potential ranges. 4. At the onset of glucose-free anoxia the epifluorescence of
      individual myocytes studied in the single excitation (490 nm)-double emission
      (530 and 590 nm) mode showed a gradual decline of the aggregate emission, which
      reached a plateau while electrically stimulated (0.2 Hz) contraction was still
      retained. The subsequent failure of contraction was followed by the rise of the
      emission at 530 nm, corresponding to the monomer form of the dye, concomitantly
      with the development of rigor contracture. 5. The onset of the rigor was preceded
      by the increase in intracellular Mg2+ concentration ([Mg2+]i) monitored by mag
      indo-1 epifluorescence. Since under these experimental conditions intracellular
      [Ca2+] and pH are fairly stable, the increase in [Mg2+]i was likely to be
      produced by a decrease in ATP content. 6. The inhibition of mitochondrial ATPase
      induced by oligomycin during anoxia was associated with a rapid and simultaneous
      change of both the components of JC-1 fluorescence, suggesting that delta psi m,
      instead of producing ATP, is generated by glycolytic ATP during anoxia. 7. The
      readmission of oxygen induced a rapid decrease of the monomer emission and a
      slower increase of the aggregate emission. These fluorescence changes were not
      necessarily associated with the recovery of mechanical function.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7562626
TI  - Involvement of dihydropyridine receptors in terminating Ca2+ release in rat
      skeletal myotubes.
AB  - 1. Combined patch-clamp and fura-2 measurements were performed in order to
      investigate the effect of dihydropyridine (DHP) antagonists on termination of
      sarcoplasmic reticulum (SR) Ca2+ release in cultured rat skeletal myoballs. 2.
      Ca2+ transients induced by 10 mM caffeine were curtailed by depolarization (e.g.
      +20 mV for 1 s) and subsequent repolarization (-70 mV). This phenomenon is termed
      RISC (repolarization-induced stop of caffeine-induced Ca2+ release). 3. At 0.5 to
      1 microM, DHP antagonists (nifedipine or (+)PN200-110) strongly inhibited RISC
      and also slowed the decay of intracellular Ca2+ concentration ([Ca2+]i) following
      repolarization after depolarization-induced Ca2+ release (-20 or -10 mV for 5 s).
      4. The activation time course of the Ca2+ channel associated with the DHP
      receptor (DHPR) was investigated by measuring DHP-sensitive Ca2+ channel tail
      currents, while varying the duration of depolarizing pulses. The tail currents
      increased with pulse duration and peaked around 0.7, 0.9 and 1.1 s for
      depolarizations to +70, +40 and +20 mV, respectively. These values are compatible
      with the activation time course of RISC (0.5-1 s to maximally activate RISC at
      +20 to +60 mV). 5. These results suggest that the DHPR in T-tubular membranes
      regulates closing of the ryanodine receptor (RyR)-Ca2+ release channel complex
      through membrane potential change.

PMID- 7562627
TI  - Arachidonic acid and diacylglycerol release associated with inhibition of myosin
      light chain dephosphorylation in rabbit smooth muscle.
AB  - 1. Exogenous arachidonic acid (AA) inhibits the protein phosphatase that
      dephosphorylates smooth muscle myosin, thus sensitizing the contractile response
      to Ca2+; it also inhibits voltage-gated Ca2+ channels in smooth muscle. The
      purpose of the present study was to determine whether endogenous AA is increased
      by agonists in a manner consistent with its role as a messenger regulating myosin
      phosphatase and Ca2+ channels. Both AA and diacylglycerol (DAG) were measured in
      [3H]AA-labelled intact and permeabilized (with staphylococcal alpha-toxin) rabbit
      femoral arteries stimulated with the alpha 1-adrenergic agonist phenylephrine
      (PE) (intact and permeabilized smooth muscles) or by guanosine-5'-O-(3
      thiotriphosphate (GTP gamma S; permeabilized smooth muscles in which the [Ca2+]
      was maintained constant). Arachidonic acid mass was determined with gas
      chromatography and mass spectrometry (GC-MS). 2. In intact smooth muscle, PE
      increased both AA and DAG levels significantly, to 210 and 145% of baseline
      values, respectively. Another Ca2+-sensitizing agent, the thromboxane analogue
      U46619, caused a similar increase in AA and DAG levels in rabbit pulmonary
      artery. 3. In permeabilized smooth muscle at constant [Ca2+](pCa 6.5) GTP gamma S
      induced AA and DAG release preceded force development and GTP gamma S (50 microM,
      10 min) increased AA mass to 61-88 microM. 4. Phorbol-12,13-dibutyrate (PDBu),
      another Ca2+-sensitizing agent, also increased both AA and DAG levels in
      permeabilized smooth muscle at pCa 6.5, whereas the inactive analogue, 4 alpha
      phorbol, did not have a Ca2+-sensitizing effect, nor did it increase AA and DAG
      levels. 5. In the virtual absence of Ca2+ (pCa > 8) GTP gamma S also increased AA
      and DAG levels by 3.5- and 1.6-fold, respectively. The effect of free Ca2+ itself
      on AA and DAG release was modest in the physiological range (pCa 7.0 to pCa 6.0),
      but pCa 4.5 caused an approximately 3- to 4-fold increase in AA and DAG levels,
      compared with the levels at pCa 8. In permeabilized ileum smooth muscle
      maintained at constant [Ca2+] (pCa 6.0), carbachol also significantly increased
      AA to 1.75 times its original value within 1 min of its application. 6. Our
      results are consistent with, although do not prove, the roles of AA and DAG as
      second and/or co-messenger(s) in smooth muscle, while the increases in AA and DAG
      levels induced by PDBu raise the possibility that they contribute to some of the
      cellular effects of phorbol esters.

PMID- 7562629
TI  - Chimeric L-type Ca2+ channels expressed in Xenopus laevis oocytes reveal role of
      repeats III and IV in activation gating.
AB  - 1. Chimeric alpha 1 subunits consisting of repeat I and II from the rabbit
      cardiac (alpha 1C-a) and repeat III and IV from the carp skeletal muscle Ca2+
      channel (alpha 1S) were constructed and expressed in Xenopus laevis oocytes
      without co-expressing other channel subunits. Ba2+-current kinetics of five
      chimeric channel constructs were studied in Xenopus oocytes using the two
      microelectrode technique. 2. Exchange of repeats III and IV of alpha 1C-a with
      sequences of alpha 1S results in a significantly slower and biexponential
      activation (apparent activation time constants tau 1act = 19.8 +/- 1.8 ms and tau
      2act = 214 +/- 28.7 ms, n = 7) of expressed Ca2+ channel currents; no current
      inactivation was observable during an 800 ms test pulse to 0 mV. 3. Activation of
      a chimera consisting of repeats I, II and IV from the alpha 1C-a subunit and
      repeat III from alpha 1S was fast and monoexponential (tau 1act = 6.33 +/- 1.7
      ms, n = 5) and the current inactivated during a 350 ms test pulse to 0 mV (tau
      inact = 175 +/- 22 ms, n = 5). The current kinetics of this construct did not
      significantly differ from kinetics of a construct consisting of repeats I to IV
      from alpha 1C-a (tau 1act = 6.6 +/- 2.1 ms; tau inact = 198 +/- 14 ms; n =
      9).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562628
TI  - H2O2-induced chloride currents are indicative of an endogenous Na(+)-Ca2+
      exchange mechanism in Xenopus oocytes.
AB  - 1. Defolliculated Xenopus oocytes were voltage clamped in bathing solutions
      containing 115 mM KCl and 1.8 mM CaCl2. External application of H2O2 transiently
      elicited voltage-dependent outward rectifying currents within several seconds.
      Upon depolarization to +50 mV these currents had an activation time constant of
      370 ms and reached amplitudes of up to 70 microA. This current was also observed
      in oocytes without the vitelline membrane. 2. The current was abolished by 500
      microM niflumic acid, by the replacement of external Cl- by methanesulphonate, or
      when extracellular Ca2+ was removed indicating the involvement of Ca2+-activated
      Cl- channels, which are very abundant in Xenopus oocytes. 3. While the current
      could be recorded in bathing solutions containing Li+, K+, Rb+, Cs+ and NH4+,
      extracellular Na+ abolished the current completely (IC50 = 6 mM Na+). 4. The H2O2
      induced Cl- current was half-maximally blocked by approximately 25 microM 2'4'
      dichlorobenzamil, 250 microM MgCl2, 100 microM CdCl2 and 100 microM NiCl2. These
      substances have been shown to block Na+-Ca2+ exchangers in various tissues. 5.
      The data are consistent with the existence of an endogenous Na+-Ca2+ exchanger in
      the plasma membrane of Xenopus oocytes, which runs in reverse mode in the absence
      of high external Na+ and the presence of external Ca2+. This endogenous component
      has to be considered when Xenopus oocytes are used for heterologous expression
      studies.

PMID- 7562630
TI  - Functional expression of the tachykinin NK1 receptor by floor plate cells in the
      embryonic rat spinal cord and brainstem.
AB  - 1. The floor plate is a ventral mid-line structure that plays a pivotal role in
      the organization of the developing vertebrate central nervous system. Previous
      studies have demonstrated that the floor plate may provide signals that induce
      neuronal differentiation and guide axons; however, it is not known whether the
      floor plate can itself respond to signals that derive from surrounding tissue. 2.
      The peptide substance P is one of the first transmitters to be expressed in the
      developing spinal cord. To determine whether the floor plate may respond to
      substance P we have examined the expression of the principal substance P receptor
      (the tachykinin NK1 receptor) by floor plate cells of the rat embryonic spinal
      cord using immunocytochemistry, in situ hybridization and fura-2 calcium imaging.
      3. Immunocytochemistry demonstrated selective expression of the NK1 receptor by
      cells at the ventral mid-line of the spinal cord. Double immunofluorescence
      labelling with the specific floor plate marker FP3 indicated that NK1 receptor
      expression is confined to cells in the lateral region of the floor plate. 4. In
      order to confirm the specificity of the NK1 receptor immunoreactivity we
      performed in situ hybridization histochemistry using antisense cRNA probes
      directed against the NK1 receptor. In situ hybridization demonstrated selective
      expression of NK1 receptor mRNA by floor plate cells. 5. The ontogeny of NK1
      receptor protein and mRNA expression in the floor plate was defined. NK1 receptor
      expression occurred in a rostrocaudal progression that begins at embryonic day 10
      11 (E10-E11) and is complete by E12-E14. The restriction of NK1 receptor
      expression to the lateral part of the floor plate was conserved throughout
      embryonic development. 6. NK1 receptor signalling was assessed by monitoring
      substance P-evoked changes in the intracellular concentration of calcium ions
      ([Ca2+]i) of acutely dissociated cells from the floor plate region. Application
      of substance P (5 nM) elevated [Ca2+]i in 10% of cells examined. 7. Selective
      neurokinin agonists were used to identify the receptor subtype involved in the
      substance P-evoked elevation of [Ca2+]i. Acetyl-[Arg6,Sar9,Met(O2)11]-substance
      P(6-11) (5 nM) and [Sar9,Met(O2)11]-substance P (5 nM), two highly selective NK1
      receptor agonists, both elevated [Ca2+]i in floor plate cells that responded to
      substance P. [beta-Ala8]-neurokinin A(4-10) (50 nM) and senktide (50 nM),
      selective agonists respectively of NK2 and NK3 receptors, had no effect on
      [Ca2+]i.

PMID- 7562631
TI  - Increased perinuclear Ca2+ activity evoked by metabotropic glutamate receptor
      activation in rat hippocampal neurones.
AB  - 1. The effect of metabotropic glutamate receptor activation on intracellular Ca2+
      activity (alpha Cai) of rat hippocampal pyramidal neurones in vitro was examined
      using ratiometric confocal laser scanning microscopy with the Ca(2+)-sensitive
      fluorescent probe indo-1 AM. 2. Metabotropic receptors were selectively activated
      with 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 100 microM) in
      the presence of D-2-amino 5-phosphonovaleric acid (D-APV), 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) and CdCl2. Most pyramidal neurones (77/84)
      responded with an elevation in Ca2+ activity, maximal after 3-5 min. Fluorescence
      ratio responses were concentration dependent (EC50 approximately 10 microM) and
      were blocked by prior application of the antagonist (RS)-4-carboxy-3
      hydroxyphenylglycine (RS-CHPG, 300 microM). 3. Responses to 1S,3R-ACPD (100
      microM) also caused acidification of the neurones, from estimated control pH 7.2
      to pH 6.6 (measured with the pH-sensitive dye SNAFL-calcein). The correction
      factor for indo-1 determination of Ca2+ was estimated to be x 1.4. 4. Elevations
      in alpha Cai were greater within the perinuclear region (> 1000 nM), than in the
      cytoplasm (approximately 200 nM). This region was devoid of staining by the
      endoplasmic reticulum staining dye 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)).
      5. It is concluded that activation of metabotropic receptors in immature rat
      hippocampal pyramidal neurones leads to a large increase in perinuclear Ca2+
      which would be well positioned to interact with the genome.

PMID- 7562633
TI  - Presynaptic metabotropic glutamatergic regulation of inhibitory synapses in rat
      cerebellar slices.
AB  - 1. The effects of the metabotropic glutamate agonist trans-ACPD (t-ACPD) were
      investigated in various locations of the inhibitory network made by GABAergic
      interneurones in the molecular layer of rat cerebellar slices. 2. t-ACPD exerted
      complex effects on spontaneous IPSCs in Purkinje cells. IPSC frequency was
      transiently inhibited during short (< 1 min) applications, and enhanced upon
      washing. During prolonged exposure to t-ACPD, IPSCs became organized in high
      frequency bursts interspersed with periods of deep inhibition. 3. In
      interneurones, the frequency of spontaneous IPSCs was enhanced by t-ACPD. As in
      Purkinje cells, spontaneous IPSCs had a tendency to cluster in bursts in the
      presence of t-ACPD. 4. Evoked IPSCs recorded either in interneurones or in
      Purkinje cells upon stimulation of presynaptic interneurones were reversibly
      inhibited by t-ACPD. 5. Miniature IPSCs (mIPSCs) were recorded in the presence of
      tetrodotoxin both in Purkinje cells and in interneurones. t-ACPD did not alter
      the mean amplitude of mIPSCs in either cell type. It reduced the frequency of
      mIPSCs in Purkinje cells, but did not alter their rate in interneurones. 6. In
      cell-attached recordings on interneurone somata, t-ACPD was found to induce
      clustering of action potentials and to enhance the mean rate of firing. These
      results apply whether t-ACPD was tested in normal saline, in the presence of
      glutamatergic ionotrophic blockers, or in the presence of a mixture of
      glutamatergic and GABAergic blockers. 7. The results suggest that t-ACPD has at
      least two different modes of action. One effect is to alter the intrinsic firing
      rate of interneurones, presumably through an action on somatic conductance
      mechanisms. The other is to decrease the efficacy of the interneurone
      interneurone and interneurone-Purkinje cell synapses, presumably through an
      action on axonal conductance systems and/or vesicle release mechanisms.

PMID- 7562632
TI  - Potassium currents in adult rat intracardiac neurones.
AB  - 1. Properties of K+ currents were studied in isolated adult rat parasympathetic
      intracardiac neurones with the use of single-electrode voltage-clamp techniques.
      2. A hyperpolarization-activated inward rectifier current was revealed when the
      membrane was clamped close to the resting level (-60 mV). The slowly developing
      inward relaxation had a mean amplitude of 450 pA at -150 mV, an activation
      threshold of -60 to -70 mV and a relaxation time constant of 41 ms at -120 mV.
      The current was reversibly blocked by Cs+ (1 mM) and became smaller with reduced
      [K+]o and [Na+]o, indicating that this inward rectifier current probably is a
      time- and voltage-dependent Na(+)-K+ current. 3. Step depolarizations from the
      holding potential of -80 mV evoked a transient (< 100 ms at -40 mV) outward K+
      current (IA) which was blocked by 4-aminopyridine (4-AP, 1 mM). The time
      constants for IA inactivation were 20 ms at -50 mV and 16 ms at -20 mV. The
      steady-state activation and (removal of) inactivation curve showed a small
      overlap between -70 and -40 mV; the reversal potential of IA was close to EK. 4.
      Step hyperpolarizations from the depolarized potentials, i.e. -30 mV, revealed a
      slow inward relaxation associated with the deactivation of a time- and voltage
      dependent current. The inward relaxation became faster at more hyperpolarized
      potentials and reversed at -85 and -53 mV in 4.7 and 15 mM [K+]o. This current
      was blocked by muscarine (20 microM) and Ba2+ (1 mM) but not affected by Cs+ (1
      mM); this current may correspond to the M-current (IM). 5. Depolarization
      activated outward K+ currents were evoked by holding the membrane close to the
      resting potential in the presence of tetrodotoxin (TTX, 3 microM), 4-AP (1 mM)
      and Ba2+ (1 mM). The amplitude of the outward relaxation and the tail current
      became smaller as the [K+]o was elevated. The outward tail current was reduced in
      a Ca(2+)-free solution and the residual current was eliminated by the addition of
      tetraethylammonium (TEA, 10 mM); the reversal potential was shifted in a
      direction predicted by the Nernst equation. These findings suggest the presence
      of delayed rectifier K+ current and Ca(2+)-activated K+ current. 6. Superfusion
      of TEA, Ba2+ and 4-AP, but not Cs+, induced rhythmic discharges in some of the
      otherwise quiescent intracardiac neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7562637
TI  - The electrical activity of mouse pancreatic beta-cells recorded in vivo shows
      glucose-dependent oscillations.
AB  - 1. The characteristics of the electrical activity of beta-cells from islets of
      Langerhans recorded in vivo are described. For blood glucose concentrations from
      4 to 11 mM, the electrical activity of pancreatic beta-cells is oscillatory, with
      alternating depolarized and hyperpolarized phases. During the depolarized phases,
      action potentials are triggered. 2. The main effect of increasing glucose
      concentration consists of an increase in the duration of the depolarized phase.
      The relationship between blood glucose concentration and the percentage of time
      in the depolarized phase can be described by a sigmoidal function with half
      activation at 6.8 mM glucose. The equivalent value obtained in parallel
      experiments in vitro is 13.3 mM, a significant rightward shift in the activation
      curve that suggests a role for other neural or humoral factors in determining the
      islet sensitivity to glucose. 3. The injection of glucose into the bloodstream
      produces a transitory phase of continuous electrical activity that is recorded
      within seconds after the change and that leads to a decrease of the glycaemia to
      the prestimulatory value. 4. The results demonstrate that under physiological
      conditions the electrical response of beta-cells to glucose consists of membrane
      potential oscillations, validating previous data obtained with isolated
      preparations. Furthermore, the electrical response occurs at lower levels of
      glycaemia than those predicted from recordings in isolated preparations and is
      maximal within the physiological range of blood glucose.

PMID- 7562634
TI  - Ca(2+)-induced Ca2+ release and its activation in response to a single action
      potential in rabbit otic ganglion cells.
AB  - 1. Ryanodine-sensitive intracellular Ca2+ release activated by Ca2+ entry was
      studied with fura-2 fluorescence and intracellular voltage recording techniques
      in rabbit otic ganglion cells. 2. The removal of extracellular Ca2+ reduced
      sustained, transient or oscillatory rises in intracellular Ca2+ ([Ca2+]i) induced
      at high extracellular K+ and abolished the [Ca2+]i oscillation in cultured
      neurones. 3. Ryanodine (10 microM) transiently increased [Ca2+]i and reduced the
      amplitude and rate of rise of the high-K(+)-induced rise in [Ca2+]i, while
      caffeine (5 mM) produced a few transient rises in [Ca2+]i in most cultured cells
      and [Ca2+]i oscillation only in one cell. 4. The two components of the slow after
      hyperpolarization (AHP) of an action potential in neurones of freshly isolated
      ganglia were dependent on extracellular Ca2+ and abolished by Ca2+ channel
      blockers, Cd2+ or Co2+. 5. The late component of AHP (LAHP), but not the initial
      component, in 'fresh' neurones increased in area with an increase in the
      preceding interval, was abolished by ryanodine (10 microM) and intracellularly
      injected EGTA, and mimicked by intracellular injection of Ca2+. 6. A ryanodine
      sensitive Ca(2+)-induced Ca2+ release thus exists, operates in response to an
      action potential-induced Ca2+ entry and underlies LAHP in rabbit otic ganglion
      cells.

PMID- 7562638
TI  - The effects of lyotropic anions on electric field-induced guidance of cultured
      frog nerves.
AB  - 1. Dissociated Xenopus neurites turn cathodally in small applied electric fields.
      Increasing the external polycation concentration alters the direction and extent
      of field-induced orientation. A decrease in membrane surface charge may underlie
      these effects. 2. Lyotropic anions increase membrane surface charge and we have
      examined the effect of perchlorate (ClO4-), thiocyanate (SCN-) and sulphate
      (SO4(2-)) on galvanic nerve orientation. 3. Perchlorate and SCN- had no effect on
      field-induced cathodal turning, whereas incubation with SO4(2-) was inhibitory.
      In addition to its effects on surface charge, SO4(2-) increases production of the
      second messengers diacylglycerol and inositol trisphosphate. Interestingly,
      lithium (Li+), a blocker of polyphosphoinositide metabolism, had a similar effect
      to SO4(2-) on field-induced neurite orientation. 4. We conclude that increasing
      surface charge with lyotropic anions neither enhances galvanotropic orientation
      nor underlies the inhibitory effects of SO4(2-) and suggest that modulation of
      galvanotropism by SO4(2-) occurs owing to changes in the inositolphospholipid
      second messenger system.

PMID- 7562636
TI  - Characterization of spontaneous excitatory synaptic currents in salamander
      retinal ganglion cells.
AB  - 1. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under
      voltage-clamp conditions. Consistent with activation of non-NMDA-type glutamate
      receptors, the sEPSCs reversed at potentials above 0 mV, were blocked by 1 microM
      CNQX and prolonged by 2 mM aniracetam. 2. The peak conductance of the averaged
      sEPSCs (n = 70-400) was 130 +/- 60 pS (mean +/- S.D.; 17 cells, ranging from 70
      to 290 pS). Amplitude distributions were skewed towards larger amplitudes. 3. The
      decay of individual and mean sEPSCs was exponential with a mean time constant
      (tau d) of 3.75 +/- 0.84 ms (n = 13), which was voltage independent. The 10-90%
      rise time of the sEPSCs was 1.30 +/- 0.44 ms (n = 13). There was no correlation
      between sEPSC rise time and tau d suggesting that dendritic filtering alone did
      not shape the time course of sEPSCs. 4. Light-evoked EPSCs in these retinal
      ganglion cells are mediated by concomitant activation of NMDA and non-NMDA
      receptors; however, no NMDA component was discerned in the sEPSCs, even when
      recording at -96 mV in Mg(2+)-free solutions. The decay time course was not
      altered by 20 microM AP7, an NMDA antagonist, nor was an NMDA component unmasked
      by adding glycine or D-serine. These results suggest that NMDA and non-NMDA
      receptors are not coactivated by a single vesicle of transmitter during
      spontaneous release, and thus are probably not colocalized in the postsynaptic
      membrane at the sites of spontaneous release. 5. The sEPSCs were an order of
      magnitude faster than the non-NMDA receptor-mediated EPSCs evoked by light
      stimuli, and it is proposed that the EPSC time course is determined largely by
      the extended time course of release of synaptic vesicles from bipolar cells. The
      quantal content of a light-evoked non-NMDA receptor-mediated EPSC in an on-off
      cell is about 200 quanta.

PMID- 7562635
TI  - Activation of recombinant mouse acetylcholine receptors by acetylcholine,
      carbamylcholine and tetramethylammonium.
AB  - 1. The kinetic properties of cloned mouse embryonic nicotinic acetylcholine
      receptors (AChRs) expressed in HEK 293 cells or Xenopus oocytes were examined
      using high concentrations of acetylcholine (ACh), carbamylcholine (CCh), or
      tetramethylammonium (TMA). The rate constants of agonist binding and channel
      gating were estimated by fitting kinetic models to idealized open and closed
      intervals over a range of agonist concentrations. 2. Once doubly liganded, TMA
      activated receptors open at approximately 3000 s-1. The equilibrium binding
      constants for TMA are 525 and 12,800 microM. Doubly liganded CCh-activated
      receptors open at approximately 11,500 s-1; the equilibrium binding constants for
      this agonist are 14 and 570 microM. If we assume that doubly liganded, ACh
      activated receptors open at 60,000 s-1, then the equilibrium binding constants
      for ACh are 20 and > 650 microM, similar to those for CCh. For all three agonists
      the higher affinity site both binds and releases agonists more slowly than does
      the lower affinity site. 3. ACh and CCh bind to the two sites equally rapidly, at
      approximately 2 x 10(7) and 4 x 10(7) M-1 s-1 at the first and second binding
      sites, respectively. Compared with ACh, the TMA association rate is approximately
      100 times slower at the first binding site, and approximately 30 times slower at
      the second binding site. These results indicate that at both binding sites the
      association rate of TMA is not limited by diffusional or steric factors. 4. All
      three agonists dissociate from the receptor binding sites at similar rates. The
      dissociation rate for all agonists was approximately 40 times slower at the first
      binding site than at the second. These results suggest that the interaction of
      the quarternary amine moiety with the receptor determines the rate of release of
      the agonist, and that the nature of this interaction is quite different at the
      two binding sites. 5. Although the channel opening rates for the three agonists
      varied approximately 20-fold, the channel closing rates were not strongly agonist
      dependent, and varied less than 3-fold. We speculate that the ester moiety of the
      agonist promotes both rapid binding and fast opening of the ligand receptors, and
      that interactions of the quarternary amine moiety of the agonist with the
      receptor determine the channel closing rate constant.

PMID- 7562639
TI  - Analysis of bursting responses of oxytocin neurones in the rat in late pregnancy,
      lactation and after weaning.
AB  - 1. Electrophysiological recordings were undertaken to compare bursting
      characteristics of oxytocin (OT) neurones at four reproductive stages: day 20
      pregnancy, day 22 of pregnancy (expected day of parturition), day 7-11 of
      lactation, and day 5-6 after weaning. 2. Each OT neurone was recorded for 1 h of
      suckling, combined with cervico-vaginal probing at 5 min intervals as an
      additional stimulus for bursting. Intracerebroventricular (I.C.V.) oxytocin (2.2
      ng) was given after 30 min to facilitate bursting responses. Bursts observed
      during suckling were classified as 'spontaneous' or 'probe-evoked'. 3. The
      percentage of cells displaying spontaneous and/or probe-evoked bursts during the
      recording was low in day 20 pregnant animals, high in lactators and intermediate
      in day 20 pregnant and weaner groups. These differences may relate to variation
      in the proportion of animals with a responsive milk-ejection reflex, as well as
      the relative size of the population of bursting OT neurones. 4. In the period
      before I.C.V. OT, overall burst frequency (including both spontaneous and probe
      evoked bursts) was similar across groups. After I.C.V. OT, overall burst
      frequency was much higher in lactators compared with other groups. Similar
      results were obtained when spontaneous bursts were analysed separately. 5. Burst
      amplitude (action potentials per burst, including both spontaneous and probe
      evoked bursts) prior to I.C.V. OT was similar between the day 20 pregnant, day 22
      pregnant and lactating groups, but was lower in weaners. All groups showed an
      increase in burst amplitude after I.C.V. OT, but values in weaners remained lower
      than in other groups. In a separate analysis of spontaneous bursts, burst
      amplitude after I.C.V. OT was higher in lactators, and lower in weaners, than in
      pregnant animals. 6. Background firing rates of OT cells were higher in the day
      20 and day 22 pregnant groups compared with lactators, and lower in weaners. Only
      OT cells in lactators showed a significant increase in background firing rates
      following I.C.V. OT. 7. It is concluded that the bursting characteristics of OT
      cells change markedly between late pregnancy, mid-lactation and weaning. The
      factors underlying these changes, which are only loosely correlated with the
      sequence of morphological adaptations in OT cells surrounding lactation, remain
      to be established.

PMID- 7562640
TI  - Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on
      breathing movements in fetal sheep in utero.
AB  - 1. We studied the effects of systemic administration of the alpha 1- and alpha 2
      adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor
      antagonist prazosin on fetal breathing movements (FBM) and electrocortical
      activity (ECoG) in fetal sheep. In one group of fetuses (group I; n = 7) the
      effects of phentolamine were measured during normoxia and hypoxia. In the second
      group of fetuses (group II; n = 8) the effects of either phentolamine, or
      combined phentolamine and prazosin, or prazosin alone, were measured during
      normoxia. 2. In group I fetuses, the incidence of FBM increased after
      phentolamine treatment. An increase in the incidence and mean episode duration of
      low-voltage ECoG (LV-ECoG) was also measured after phentolamine treatment. These
      effects of phentolamine persisted during hypoxia. 3. In group II fetuses a
      pronounced decrease in the incidence of FBM occurred after administration of
      prazosin following either phentolamine or saline pretreatment. These effects of
      prazosin on FBM were independent of an effect on ECoG activity. 4. We conclude
      that catecholamines have a stimulatory role on FBM mediated via an alpha 1
      adrenoreceptor mechanism. Phentolamine leads to an increase in FBM by
      preferentially antagonizing presynaptic alpha 2-adrenoreceptors over postsynaptic
      alpha 1-adrenoreceptors. This influence of phentolamine on FBM may be secondary
      to its effect on ECoG. Promotion of LV-ECoG by catecholamines is mediated via an
      alpha 1-independent mechanism.

PMID- 7562641
TI  - Ozone-induced oxygen radical release from bronchoalveolar lavage cells and airway
      hyper-responsiveness in dogs.
AB  - 1. Ozone inhalation causes airway hyper-responsiveness and airway inflammation in
      dogs. The purpose of this study was to determine whether these effects are
      associated with increases in oxygen radical production from bronchoalveolar
      lavage (BAL) cells. 2. Twelve randomly selected dogs were studied twice, 4 weeks
      apart. On each study day, acetylcholine (ACh) airway responsiveness was measured
      before and 1 h after ozone (3 p.p.m., 30 min) or dry air inhalation, followed by
      BAL. The response to ACh was expressed as the concentration causing an increase
      in lung resistance of 5 cmH2O l-1 s-1 above baseline. Spontaneous and phorbol
      myristate acetate (PMA) (2.4 mumol l-1)-stimulated oxygen radical release from
      washed BAL cells (4 x 10(6) cells ml-1) was measured by luminol-enhanced
      chemiluminescence in a luminometer at 37 degrees C. 3. Ozone inhalation caused
      airway hyper-responsiveness. The concentration of ACh causing an increase in lung
      resistance of 5 cmH2O l-1 s-1 (the 'provocative' concentration) fell from 4.68 mg
      ml-1 (% S.E.M., 1.43) before, to 0.48 mg ml-1 (% S.E.M., 1.60) after ozone (P <
      0.0001). Spontaneous chemiluminescence area under the curve (AUC) significantly
      increased after ozone from 4.08 mV (10 min) (% S.E.M., 1.28) after dry air to
      8.25 mV (10 min; % S.E.M., 1.29) after ozone (P = 0.007). Ozone inhalation also
      increased PMA-stimulated chemiluminescence AUC from 18.97 mV (10 min; % S.E.M.,
      1.18) after dry air to 144.03 mV (10 min; % S.E.M., 1.45) after ozone (P =
      0.0001). The increase in PMA-stimulated chemiluminescence was significantly
      correlated with ozone-induced ACh airway hyper-responsiveness (r = 0.83, P <
      0.001). 4. These results indicate that inhaled ozone increases oxygen radical
      release from BAL cells and suggest that oxygen radicals are important in causing
      ozone-induced airway hyper-responsiveness.

PMID- 7562642
TI  - Hypoxic changes in rat locus coeruleus neurons in vitro.
AB  - 1. Intracellular recordings were made in a pontine slice preparation of the rat
      brain containing the nucleus locus coeruleus (LC). Locus coeruleus neurons
      responded to brief hypoxic stimuli (replacement of 95% O2-5% CO2 with 95% N2-5%
      CO2) with hyperpolarization and a cessation of spontaneous action potentials.
      When the cells were continuously hyperpolarized by about 15 mV in order to
      abolish spontaneous firing, hypoxia induced an early depolarization (HD),
      followed by a hypoxic hyperpolarization (HH) and after reoxygenation, a
      posthypoxic hyperpolarization (PHH). These responses were accompanied by a
      decrease in input resistance, which was larger during HH than during HD but,
      thereafter, became smaller during PHH. 2. The hypoxia-induced currents associated
      with the changes in membrane potential, at a holding potential of -70 mV, were an
      early inward current (HIC), a subsequent outward current (HOC) and after
      reoxygenation, another outward current (PHOC). The HIC did not change with an
      increasing holding potential. In contrast, the HOC reversed its amplitude at
      about -95 mV. Finally, the PHOC decreased, but did not reverse its polarity at
      more negative holding potentials. When the external K+ was elevated from 2.5 to
      10.5 mM, the current-voltage (I-V) relation of the HOC and its reversal potential
      were shifted to the right. 3. In the presence of tetrodotoxin, the HH decreased.
      A low Ca(2+)-high Mg2+ medium depressed both the HH and PHH. Rauwolscine did not
      alter either response to hypoxia, while 8-cyclopentyl-1,3-dipropylxanthine
      decreased the PHH only. S-(p-Nitrobenzyl)-6-thioguanosine potentiated both HH and
      PHH. 4. Whereas tolbutamide markedly lowered the HH and PHH, glibenclamide was
      ineffective. Tetraethylammonium also failed to alter the hypoxic responses.
      Furthermore, ouabain or the removal of K+ from the superfusion medium, depressed
      PHH. 5. Pressure application of adenosine inhibited the spontaneous firing of LC
      neurons. DPCPX did not alter the firing, but antagonized the effect of adenosine.
      Tolbutamide also counteracted the inhibitory effect of adenosine and,
      additionally, facilitated the firing rate in some neurons. Moreover, tolbutamide
      abolished the adenosine-induced outward current. 6. Early hypoxic depolarization
      and PHH are mostly due to the blockade and subsequent reactivation of the K(+)
      Na+ pump, respectively. The HH is caused by the opening of ATP-sensitive K+
      (KATP) channels in response to the hypoxia-induced decline of intracellular ATP.
      Adenosine released by hypoxic stimuli may lead to an adenosine A1-receptor
      mediated opening of (KATP) channels during the HH and more markedly during the
      PHH.

PMID- 7562643
TI  - Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP-sensitive
      potassium channels.
AB  - 1. Nitric oxide (NO) relaxes vascular smooth muscle (VSM) by mechanisms which are
      not fully understood. One possibility is that NO hyperpolarizes membranes,
      thereby diminishing Ca2+ entry through voltage-dependent Ca2+ channels. In the
      current study, the effects of NO on membrane potential of rabbit mesenteric
      arteries were recorded using intracellular microelectrodes. 2. NO, released by 3
      morpholinosydnonimine (SIN-1, 3 microM), reversibly hyperpolarized arteries by 
      9.5 +/- 4.0 mV (means +/- S.D., n = 97) from a resting membrane potential of 
      53.1 +/- 5.7 mV. The hyperpolarization was blocked by oxyhaemoglobin (20 microM),
      and only occurred in arteries pre-treated with N omega-nitro-L-arginine (100
      microM) or denuded of endothelium. 3. The effect of SIN-1 was concentration
      dependent (EC50 approximately 0.4 microM) and its dose response was shifted to
      the left by zaprinast (100 microM), an inhibitor of cGMP-specific
      phosphodiesterases. 4. The hyperpolarization due to SIN-1 was modified by changes
      in extracellular K+ concentration, but not by changes in Ca2+, Na+ or Cl-. The
      hyperpolarization was blocked by glibenclamide (IC50 approximately 0.15 microM),
      but not by apamin (3-300 nM), barium (5-150 microM), tetraethylammonium (0.1-10
      mM), or 4-aminopyridine (5-500 microM). The hyperpolarization due to lemakalim
      (0.03-3 microM), an activator of ATP-sensitive potassium channels (KATP),
      displayed the same sensitivities to these K+ channel blocking agents, whereas the
      endothelium-derived hyperpolarizing factor, triggered by the addition of
      acetylcholine (3 microM), caused a hyperpolarization (-15.3 +/- 6.2 mV) that was
      blocked by apamin, but not by any other agent. 5. These results suggest that NO
      hyperpolarizes VSM in rabbit mesenteric arteries by activating KATP channels,
      with the accumulation of cGMP as an intermediate step.

PMID- 7562644
TI  - Modulation of calcium-activated non-selective cation channel activity by nitric
      oxide in rat brown adipose tissue.
AB  - 1. Single-channel calcium-activated non-selective cation currents from isolated
      rat brown fat cells were measured using the inside-out patch configuration of the
      patch-clamp technique. The existence of a possible modulatory effect of nitric
      oxide on the putative redox-modulatory site located on the intracellular side of
      the non-selective cation channel was investigated. 2. The nitric oxide-releasing
      substances nitroglycerin, sodium nitroprusside, S-nitrosocysteine and S-nitroso-N
      acetyl-D,L-penicillamine (all at 100 microM) were able to block channel activity
      almost completely. 3. In each case the blockade was persistent and could not be
      washed away. Dithiothreitol (DTT, 2 mM) was able to reverse the blockade to a
      large extent, whereas oxidized DTT (2 mM) was without effect. 4. It was concluded
      that nitric oxide can modulate non-selective cation channel activity by oxidizing
      sulfhydryl groups and that this effect can be reversed by reduction.

PMID- 7562646
TI  - Modulation by magnesium of the affinity of NMDA receptors for glycine in murine
      hippocampal neurones.
AB  - 1. The effects of the divalent cation Mg2+ on NMDA currents recorded from
      cultured fetal mouse and acutely isolated neonatal rat hippocampal neurones were
      studied using the whole-cell patch-clamp technique. 2. Current-voltage relations
      were measured in the presence or absence of applied Mg2+ and added glycine. NMDA
      evoked currents were studied in the absence or in a low concentration (0.2 mM) of
      applied Ca2+ in order to minimize Ca(2+)-dependent inactivation of the responses.
      Mg2+ unexpectedly enhanced NMDA-activated currents at positive membrane
      potentials. At negative membrane potentials Mg2+ caused a previously
      characterized voltage-dependent block of inward NMDA-activated currents. 3. The
      potentiation by Mg2+ of outward currents activated by NMDA was concentration
      dependent (EC50, approximately 3 mM; Hill coefficient, approximately 2). Mg2+
      also reduced the desensitization of the NMDA receptor. The maximal enhancement of
      steady-state NMDA-activated currents was 2.7-fold and at 6 mM the time constant
      of desensitization was doubled. 4. Comparisons of concentration-response curves
      for glycine and 7-chloro-kynurenic acid demonstrated that Mg2+ significantly
      increased the affinity of the NMDA receptor for glycine. The EC50 for glycine was
      380 nM in the absence of Mg2+ and 163 nM in 3 mM Mg2+. Mg2+ had little effect on
      the forward rate of the glycine response but halved the off-rate (2.34 to 1.15 s
      1) and thus similarly reduced the apparent dissociation constant. 5. There was a
      good correlation between the concentration of extracellular Ca2+ and a reduction
      in the time constant of the glycine-sensitive component of NMDA receptor
      desensitization. Ca2+ could enhance these NMDA-activated currents briefly
      following exposure to high concentrations of Ca2+. These results are consistent
      with a Ca(2+)-dependent enhancement of the affinity of the NMDA receptor for
      glycine. 6. Mg2+ can enhance NMDA-mediated currents and reduce desensitization of
      this receptor by allosterically interacting with the glycine binding site. This
      interaction may be a key physiological mechanism through which modulation of the
      NMDA receptor is achieved.

PMID- 7562645
TI  - Effects of divalent cations on muscarinic receptor cationic current in smooth
      muscle from guinea-pig small intestine.
AB  - 1. Effects of Mg2+ and Ca2+ on muscarinic receptor cationic current (Icat) in
      guinea-pig ileal smooth muscle cells have been studied using patch-clamp
      techniques (whole-cell recording). Icat was activated either by externally
      applied carbachol or, to bypass receptors, by intracellular GTP-gamma-S. 2.
      Independently of the main permeant cation the current-voltage (I-V) relation for
      Icat was U-shaped between the reversal potential (usually 0 mV) and very negative
      potentials such as -120 mV where current could be virtually lost. Adding Ca2+ to
      Ca(2+)- and Mg(2+)-free external solution reduced inward current and made it less
      U-shaped whereas adding Mg2+ reduced inward current and shifted more positively
      the potential at which maximum inward current occurred. 3. Activation of the
      conductance underlying Icat could be described by the Boltzmann relation which
      was shifted positively by adding Ca2+ or Mg2+. Extracellular Ca2+ also distorted
      the relation by increasing the slope factor; maximal conductance was reduced in
      all cases. Icat relaxation at negative potentials was accelerated by increasing
      Mg2+ and slowed down by Ca2+. 4. These data suggest the presence of fixed
      negative surface charges on or near the muscarinic receptor cationic channel,
      which allow its modulation through alteration of surface potential. Additional
      more direct ion binding to and blocking of the channel cannot be ruled out. Some
      additional effects of Ca2+ (if compared with Mg2+) could be explained on the
      assumption that the Ca(2+)-binding activation site known to be present on the
      internal side of the channel can be accessible to Ca2+ entering through the open
      channel during muscarinic receptor stimulation, as Ca2+ ions contribute to a
      limited extent to Icat. 5. We conclude that voltage-dependent gating of
      muscarinic receptor cationic channels is an intrinsic channel property and that
      Ca2+ and Mg2+ have strong modulatory effects.

PMID- 7562647
TI  - Hyperosmotic modulation of the cytosolic calcium concentration in a rat
      osteoblast-like cell line.
AB  - 1. The effects of hyperosmotic stress on cytosolic calcium concentration
      ([Ca2+]i) were studied by ratio image analysis in single cells of an osteoblast
      like bone cell line (RCJ 1.20) loaded with fura-2 AM. 2. The ratio (340 nm/380
      nm) of steady-state [Ca2+]i in resting osteoblasts kept in Hepes-buffered medium
      was 0.82 +/- 0.04. A hyperosmotic stimulus (200 mosmol l-1 sucrose) produced a
      [Ca2+]i transient with a peak ratio of 1.28 +/- 0.09, which decayed with an
      apparent half-life (t1/2) of 42.7 +/- 2.6 s. 3. The hyperosmotically induced
      [Ca2+]i transients were insensitive to verapamil, diltiazem or nifedipine, which
      excludes the involvement of dihydropyridine-sensitive Ca2+ channels in the
      process. Non-specific Ca2+ channel blockers (Mn2+, Ni2+, La3+ or Gd3+) partially
      abolished the hyperosmotically induced [Ca2+]i elevation, indicating the
      contribution of extracellular Ca2+ influx. 4. A hyperosmotic stimulus applied in
      Ca(2+)-free medium (0.5 mM EGTA) lowered the [Ca2+]i peak to a ratio of 0.96 +/-
      0.08 (P < 0.001) compared with a Ca(2+)-containing medium. This suggests that the
      [Ca2+]i increase is due to extracellular influx, as well as release from an
      intracellular Ca2+ pool. 5. Application of thapsigargin (0.5 microM), a specific
      inhibitor of endoplasmic reticulum Ca(2+)-ATPase, in Ca(2+)-free medium caused
      transient [Ca2+]i elevation to peak ratios of 1.33 +/- 0.09, and completely
      abolished the [Ca2+]i response to a hyperosmotic stimulus. This implies the
      existence of a thapsigargin-sensitive intracellular pool of Ca2+ that is
      mobilized by hyperosmotic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562648
TI  - Rehabilitation research and development in physical medicine in Japan: a
      historical and state-of-the-art review.

PMID- 7562651
TI  - Gait initiation of persons with below-knee amputation: the characterization and
      comparison of force profiles.
AB  - The purpose of this study was to characterize gait initiation of persons with leg
      amputation and determine whether prosthetic alignment was a critical parameter in
      the initiation process. Gait initiation was chosen for study because of the
      difficult neuromuscular demands placed on the body in negotiating the transition
      from stance to ambulation. In this investigation, ground reaction force data were
      collected on seven persons with below-knee amputation. These subjects underwent a
      series of gait initiation trials while varying prosthetic alignment. An analysis
      of the data demonstrated key elements in the gait initiation process, including
      the motion of the center of gravity in preparation for steady-state walking.
      Significant asymmetries in the force profiles of the residual and nonamputated
      limbs were also found; gait initiation forces were consistently higher for the
      prosthetic limb and the timings of maxima and minima were indicative of an intact
      limb preference. Relatively small changes in prosthesis alignment proved not to
      have statistically significant effects on generalized force parameters. This
      result is consistent with the findings of other studies that gait initiation is a
      motor program with certain invariant characteristics.

PMID- 7562650
TI  - Energy expenditure during ambulation in dysvascular and traumatic below-knee
      amputees: a comparison of five prosthetic feet.
AB  - Recent advancement in prosthetic technology has led to the development of dynamic
      elastic response feet (DER), which are reported to store and release energy to
      facilitate gait. To date, there has been no objective evidence to suggest energy
      conservation while using these foot designs. The purpose of this study was to
      compare the energy expenditure of five commercially available prosthetic feet
      (SACH and four DER feet) in both the traumatic and dysvascular populations during
      level walking. Seventeen male subjects with below-knee amputation (nine traumatic
      and seven dysvascular) were tested for energy expenditure (Douglas Bag technique)
      during a 20-min walk while wearing each of the prosthetic feet. The DER
      prosthetic foot designs were not shown to reduce the energy cost (ml O2/kg-m) or
      rate of energy expenditure (ml O2/kg-min) compared to the SACH foot. Overall, the
      traumatic amputees had a similar oxygen consumption per meter traveled compared
      to the dysvascular amputees; however, the rate of energy consumption was much
      higher in the traumatic group. This increased rate was a function of the greater
      walking velocity employed by the traumatic subjects, made possible by their
      better physical fitness.

PMID- 7562649
TI  - Re: A survey of marginal wheelchair users JRRD 31(4):297-302.

PMID- 7562652
TI  - The prediction of metabolic energy expenditure during gait from mechanical energy
      of the limb: a preliminary study.
AB  - Measurements of metabolic energy consumption and free-walking velocity were
      recorded for four persons with trans-femoral amputation with variations of
      prosthesis mass and mass distribution. Hot-film anemometers, rate gyroscopes, and
      a force platform were used to measure prosthetic limb segment velocities and
      ground reaction forces. Metabolic energy consumption for the nine configurations
      of mass and mass distribution averaged 1.177 cal/kg/m with a standard deviation
      of +/- 0.052 cal/kg/m. Two measures of mechanical work of the amputated
      extremity, one based on power developed across joints (W1) and the other based on
      changes in energy of the body segments (W2), were computed to be 0.162 +/- 0.014
      and 0.175 +/- 0.025 cal/kg/m, respectively. A linear regression model led to
      rejections of both W1 and W2 as predictors of metabolic energy expenditure of the
      amputee at a significance level of 0.05.

PMID- 7562653
TI  - The effects of thigh soft-tissue stiffness on the control of anterior tibial
      displacement by functional knee orthoses.
AB  - Using three soft-tissue analogs of variable compliances, four custom functional
      knee orthoses were evaluated for their abilities to control anterior tibial
      displacement (ATD) using an anterior cruciate ligament (ACL)-deficient surrogate
      knee model with applied forces from 25 to 250 N. These analogs had stiffnesses
      (compliance) ranging from 2.18 N/mm to 4.6 N/mm, simulating the range in the
      thigh soft-tissue compliances found in subjects ranging from sedentary
      individuals to competitive athletes. Significant differences in the ATDs allowed
      were observed between the soft-tissue analogs, orthoses, and the force applied.
      At low forces, soft-tissue compliance did not play an important role in the
      reduction of ATD; however, at high forces ATD was directly related to the soft
      tissue compliance.

PMID- 7562654
TI  - Volumetric determinations with CAD/CAM in prosthetics and orthotics: errors of
      measurement.
AB  - During the next decade CAD/CAM technique will probably become routine in
      prosthetics and orthotics, not only as a complement to manual techniques, but
      also introducing new possibilities. However, even complex and sophisticated
      techniques have errors of measurement that must be considered. Such errors are of
      two principal kinds: systematic errors and random errors. In this study we have
      evaluated the Swedish CAPOD system with respect to volumetric determinations. We
      used two types of reference objects for volume determinations: cylinders and
      amputation residual limb models. Three different sizes were examined of each type
      of object. Volume measurements with CAPOD were compared with volumes obtained by
      water immersion or mathematical calculation (cylinders only). We found a
      constant, linear systematic error of +2.5%. Such an error can easily be corrected
      for. The random error, represented by the coefficient of variation, was 0.5%,
      which means that there is a theoretical possibility to detect volume changes
      exceeding 1%. We consider the precision sufficient for clinical practice in
      prosthetics and orthotics. Biological variations due to soft tissue deformation
      must be added on top of these errors. Such deformations were not evaluated in
      this study.

PMID- 7562656
TI  - Experiments in dysarthric speech recognition using artificial neural networks.
AB  - In this study, we investigated the use of artificial neural networks (ANNs) to
      recognize dysarthric speech. Two multilayer neural networks were developed,
      trained, and tested using isolated words spoken by a dysarthric speaker. One
      network had the fast Fourier transform (FFT) coefficients as inputs, while the
      other network had the formant frequencies as inputs. The effect of additional
      features in the input vector on the recognition rate was also observed. The
      recognition rate was evaluated against the intelligibility rating obtained by
      five human listeners and also against the recognition rate of the Introvoice
      commercial speech-recognition system. Preliminary results demonstrated the
      ability of the developed networks to successfully recognize dysarthric speech
      despite its large variability. These networks clearly outperformed both the human
      listeners and the Introvoice commercial system.

PMID- 7562655
TI  - An animal model and computer-controlled surface pressure delivery system for the
      production of pressure ulcers.
AB  - Pressure ulcers continue to be a major health care problem. This paper describes
      an animal model and surface pressure delivery system for the production of
      experimentally derived pressure ulcers. A method for inducing dermal pressure
      lesions on the fuzzy rat was developed using a computer-controlled displacement
      column which produced a constant tissue interface pressure. The pressure column
      consists of a force transducer located between two 0.5-in (1.27-cm) diameter
      metal cylinders. The desired cutaneous pressure is maintained by a computer
      controlled miniature stepper motor which displaces the column with the aid of
      interactive software. The force transducer signal is converted from analog to
      digital form, amplified, and recorded. Blood perfusion is monitored using a laser
      Doppler flowmeter (located in the tip of the column) during the application of
      pressure. The application of 145 mmHg pressure for 5 consecutive 6-hr sessions
      resulted in a greater than 90% incidence of pressure ulcers. The implications of
      our model and contributions of earlier animal models are discussed. This model
      provides a tightly controlled and measured environment making possible the
      scientific study of ulcer development and the evaluation of potential
      preventative or curative compounds.

PMID- 7562657
TI  - Energy cost and locomotive economy of handbike and rowcycle propulsion by persons
      with spinal cord injury.
AB  - Seven subjects with chronic paralysis due to spinal cord injury completed a
      series of experiments to 1) determine and compare the metabolic cost of
      propelling the Handbike and Rowcycle, and 2) evaluate the potential of these
      upper body-powered devices for improving the cardiorespiratory fitness of persons
      with lower limb disabilities. Mean intrasubject differences between the Handbike
      and Rowcycle rides for heart rate, minute ventilation, oxygen uptake, and net
      locomotive energy cost were small and did not reach statistical significance for
      any of the ride conditions. Lower net locomotive energy cost (greater economy)
      during a 5.5 mi.hr-1 ride condition predicted vehicle preference in all cases (P
      = 0.008). The range of values for percent peak oxygen uptake suggests that all
      but one of the subjects were able to utilize either vehicle at an intensity
      sufficient for improving and maintaining cardiorespiratory fitness without undue
      fatigue.

PMID- 7562658
TI  - Oral cancer and precancer related to betel and miang chewing in Thailand: a
      review.
AB  - Historical aspects of betel and miang chewing in Thailand are described, as is
      the betel quid. Available literature on cancer and precancer in Thailand is
      reviewed. While oral cancer has been a major health problem in the past, changes
      in habit patterns with marked reduction of betel and miang chewing during the
      last decades have prompted a change in frequency of oral cancer in some
      provinces. Oral effects of miang chewing are less marked, although chewer's
      mucosa has been observed. Betel and miang chewing seem to be vanishing habits in
      Thailand in contrast to other Southeast Asian or South Asian countries.

PMID- 7562659
TI  - Reduction in nicotine intake and oral mucosal changes among users of Swedish oral
      moist snuff after switching to a low-nicotine product.
AB  - The purpose of this investigation was to assess nicotine regulation among users
      of portion-bag Swedish oral moist snuff (snus) when switching from an ordinary
      snus product (Brand A) to a low-nicotine product having only half the
      concentration of nicotine (Brand B). Two studies were performed to compare the
      short-term effects on consumption and nicotine intake of switching to low
      nicotine snus with those of long-term effects. In Study 1, consumption data, soft
      tissue changes and nicotine intake were measured in a group of 24 habitual users
      of Swedish portion-bag snus, both during use of their ordinary snus (Brand A) for
      2 weeks and during consumption of the low-nicotine product (Brand B) for 10
      weeks. In study 2, the same data were measured during 2 weeks in a reference
      group of 18 snus users who had been habitual users of the low-nicotine snus
      (Brand B) for at least one year. Although there was no increase in number of
      hours of daily consumption, the amount of snus consumed increased on average by 2
      grams a day (+15%) when switching from Brand A to the low-nicotine Brand B (Study
      1). The Brand B reference group (Study 2) consumed about 3 grams less snus a day
      during the same number of hours as the subjects in Study 1 who had switched to
      Brand B. These results indicate that snus users compensate to a small extent for
      the lower nicotine delivery by increasing their consumption on short-term
      switching but the same does not apply to long-term users.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7562660
TI  - Lack of effect of hormonal treatment and smoking on cytokeratin expression in
      buccal mucosa.
AB  - Differences in cytokeratin expression of clinically normal buccal mucosa were
      studied in 50 healthy women by indirect immunofluorescence staining with
      monoclonal antibodies. The subjects were divided into four groups: control group
      (N = 18), smokers (N = 8), oral contraceptive users (N = 8) and smokers receiving
      oral contraceptives (N = 16). Our findings indicate that cytokeratin expression
      in noncornified stratified epithelium is not influenced by smoking or
      oestradiol/progesterone treatment. Only cytokeratin No. 19 showed variable
      patterns of expression but the differences could not be ascribed to smoking or
      contraceptives. Cytokeratin No. 19 gave a positive reaction in the basal and
      suprabasal layers in 34 subjects (68%). In 9 (18%) specimens, the staining was
      positive in the basal cells and showed a positive heterogeneous cytoplasmic
      reaction in the suprabasal cells. Interestingly, cytokeratin No. 7 was recognized
      in all epithelial cells except the basal cells. Our results suggest that changes
      in the serum oestradiol levels do not affect the cytokeratin pattern in buccal
      mucosa.

PMID- 7562661
TI  - Elevated ras p21 expression in oral premalignant lesions and squamous cell
      carcinoma in Taiwan.
AB  - Expression of ras p21 oncoproteins was examined in histological sections of oral
      squamous cell carcinoma (SCC), epithelial dysplasia, epithelial hyperkeratosis
      and normal oral mucosa using antibodies to ras p21 with an immunoperoxidase
      technique. Ras p21-positive staining was found in 47 of 51 (92.2%) cases of oral
      SCC, 4 of 4 (100%) cases of epithelial dysplasia, 7 of 7 (100%) cases of
      epithelial hyperkeratosis, and 1 of 6 (16.7%) cases of normal oral mucosa. The
      positive staining rate of ras p21 in oral SCC, epithelial dysplasia or epithelial
      hyperkeratosis was significantly higher than that in normal oral mucosa (P <
      0.05). No correlation was found between ras p21 expression and patient age,
      tumour location, tumour size, clinical staging or histological differentiation of
      SCC. However, a significant positive correlation was found between ras p21
      expression and patients' sex (P < 0.05) or regional lymph node status (P < 0.05).
      A significant positive correlation was also discovered between ras p21 expression
      and patients' smoking habits (P < 0.01), as well as daily or total betel quid
      (BQ) consumption (P < 0.05). Of the 47 immunostain-positive SCC patients,
      specimens from 6 patients were also obtained after chemotherapy, when ras p21
      expression was found to be reduced. These results indicate that ras p21
      overexpression may play an important role in the initiation and progression of
      oral SCCs in patients who are smokers and BQ chewers.

PMID- 7562662
TI  - Preliminary assessment of the epithelial nuclear-cytoplasmic ratio and nuclear
      volume density in human palatal lesions.
AB  - We have analysed both the nuclear-cytoplasmic (N/C) ratio and nuclear volume
      densities (VVN) in defined strata from human hard palate lesions with and without
      malignant potential to determine the prognostic reliability and/or validity of
      this parameter. Measurements of cellular and nuclear areas of basal and spinous
      cells from normal (N) and pathological palatal epithelium were made on
      histological sections using an image analyser. The lesions comprised fibrous
      hyperplasia (FH), traumatic inflammation (INF), benign hyperkeratosis (HK),
      squamous cell papilloma (PP), dysplastic epithelium adjacent to invasive
      carcinoma (CE) and islands of invasive squamous cell carcinoma (CI). In basal
      cells, no significant differences were detected in comparisons of N/C and VVN
      between all pathological groups and the N control group. The mean value for CE
      was lower than that obtained for N. In spinous cells, the only statistically
      significant comparison was between IF and FH for both N/C and VVN. Both
      parameters were lower in CE than in N. Of all groups analysed except CI, the CE
      group is the only one likely to possess an increased malignant potential. The N/C
      ratio therefore seems to be of no value as a predictor of malignancy in palatal
      epithelial lesions.

PMID- 7562664
TI  - Psychological factors associated with oral lichen planus.
AB  - 50 patients with oral lichen planus (LP) were investigated for current anxiety
      and depression and for related personality factors. Anxiety levels, as measured
      on the Hospital Anxiety and Depression (HAD) Scale, were elevated in 50% of cases
      while depression scores, measured on the same scale, were low in all but a few.
      The sample profile showed a slight tendency towards anxiety, as measured by the
      Cattell 16 PF Questionnaire, but did not confirm previous reports of high
      intelligence and intellectual orientation. There were no statistically
      significant associations between erosive oral LP and either anxiety or
      depression, as measured on the HAD Scale, or anxiety as measured by the Cattell
      16 PF Questionnaire.

PMID- 7562663
TI  - Relationship between mast cell degranulation and inflammation in the oral cavity.
AB  - Mast cells are granule-containing secretory cells which are distributed
      preferentially about the microvascular bed in oral mucosa. This work examined the
      contribution of mast cell mediators to inflammation in the oral cavity. Mast
      cells in oral tissues expressed the serine proteases, tryptase and chymase, with
      a minor subpopulation being chymase-negative. Mast cells contained the cytokine
      tumour necrosis factor-alpha (TNF) in their granules. Degranulation of mast cells
      was a consistent feature of inflammatory lesions (lichen planus, gingivitis,
      pulpitis, periapical inflammation). In lichen planus, intracellular stores of TNF
      were depleted, and expression of mRNA for TNF was upregulated, indicating ongoing
      production and release of the cytokine. The density of mast cells in tissue
      compartments was related to the level of expression of E-selectin, an endothelial
      adhesion molecule which is known to be induced in skin by TNF derived from
      degranulating mast cells. Further attention should be directed toward the role of
      mast cell products, particularly TNF, in inflammation in the oral cavity.

PMID- 7562665
TI  - Pseudomembranous oral candidiasis in HIV infection: ultrastructural findings.
AB  - A light and electron microscopic investigation of pseudomembranous candidiasis in
      HIV infection was undertaken as there is little data available on the
      ultrastructural features of the invasive phase of Candida in this disease. On
      examination of biopsy specimens of four patients, histopathology revealed the
      classic features of superficial candidiasis, including hyphal penetration down to
      the spinous cell layer, parakeratosis, acanthosis and spongiosis of the infected,
      superficial epithelium. However, in one case, hyphae traversed the entire
      epithelium and crossed the basal membrane, invading the adjacent connective
      tissue. Ultrastructural investigations revealed initial hyphal penetration
      through the intercellular spaces, possibly demonstrating thigmotropism. However,
      hyphal penetration was not solely confined to intercellular spaces, as some
      specimens demonstrated hyphal elements traversing both the cytoplasm and the
      nuclei of the spinous cells. In these areas of the epithelium appressoria-like
      appendages were often found at the hyphal tip. These phenomena, commonly
      described in plant fungi, have rarely been described in human material. Pools of
      desmosomes were seen in the vicinity of the hyphal pathways, implying that the
      penetration procedure is associated with detachment and congregation of
      desmosomes, possibly by enzymatic means. Interestingly, the host immune response
      to fungal invasion appeared to be minimal, as no immune-effector cells were seen
      closely associated with either the blastospores or the hyphae in any of the
      tissues examined. Whether the foregoing events are exaggerated by the abortive
      immune response seen in HIV-infected patients, or common in immunocompetent
      individuals during candidal invasion of epithelia, needs to be ascertained by
      further studies.

PMID- 7562666
TI  - Oral hairy leukoplakia in a HIV-negative asthmatic patient on systemic steroids.

PMID- 7562668
TI  - [Oil-gap method for internal perfusion and voltage clamp of single cardiac
      cells].

PMID- 7562667
TI  - Florid cemento-osseous dysplasia with concomitant simple bone cysts: a case in a
      Japanese woman.
AB  - Florid cemento-osseous dysplasia (FCOD) with concomitant simple bone cysts is not
      common. We report a case of FCOD involving three quadrants of the jaws and
      associated with two large cystic lesions of the mandible in a 40-year-old
      Japanese woman. Microscopic examination revealed unencapsulated fibroblastic
      proliferation with formation of bone and cementum, showing different
      developmental stages, and cystic lesions resembling a simple bone cyst.

PMID- 7562669
TI  - Comprehension of nonlexical categories in agrammatism.
AB  - The focus of the paper is a proposal advanced by Grodzinsky (1984, 1986, 1990)
      concerning a possible syntactic deficit in agrammatism with respect to nonlexical
      categories. Eight native speakers of Serbo-Croatian, who presented a clinical
      picture of Broca's aphasia with agrammatism, were tested. Subjects' sensitivity
      to traces and their knowledge of the inflectional and determiner system was
      investigated using a grammaticality judgment paradigm. The processing load was
      further minimized by use of short sentences that unequivocally exemplified
      different syntactic violations. These steps led to significant improvement in the
      performance of agrammatic aphasics, a result that is incompatible with the claim
      that the content of nonlexical elements is lost in agrammatism.

PMID- 7562670
TI  - Somatoform and personality disorders: personality and the soma.

PMID- 7562671
TI  - Somatoform disorders and personality traits.

PMID- 7562672
TI  - Somatoform and personality disorders: syndromal comorbidity and overlapping
      developmental pathways.
AB  - We review the literature on the relationship between somatoform disorders and
      personality disorders, which reveals that approximately two in three patients
      with a somatoform disorder meet criteria for a personality disorder. We suggest
      that the most clinically salient problems presented by patients with somatoform
      disorders reflect dysfunctions of personality. We also examine research on the
      childhood antecedents of somatoform disorders and argue for reconsidering
      somatoform disorders, along with personality disorders, as disorders of
      development. Our argument involves rejecting the traditional approach to
      classification in favour of a prototypical polythetic view. We also suggest that
      the perspectives of developmental psychopathology and life-span research offer
      more to this field than the search for biological substrates or principles based
      on descriptive psychopathology, which to date have yielded meagre research
      findings with limited clinical utility.

PMID- 7562673
TI  - Beyond specificity: effects of serotonin and serotonergic treatments on
      psychobiological dysfunction.
AB  - Serotonin is a ubiquitous neurotransmitter with widespread projections that
      provide for the involvement of serotonin in the regulation of many biological and
      psychological functions. A variety of serotonin receptor subtypes exist that
      mediate overlapping psychobiological functions and that are targets for a new
      generation of medications. Although these new generation medications appear to
      possess great biochemical specificity, their actions extend to many psychiatric
      disorders, reflecting the many interactions of serotonergic subsystems.

PMID- 7562674
TI  - Psychosocial correlates of immune responsiveness and illness episodes in US Air
      Force Academy cadets undergoing basic cadet training.
AB  - This study examined psychosocial correlates of immune function and illness in 89
      male first-year US Air Force Academy cadets. A psychosocial questionnaire was
      administered to cadets prior to their arrival at the academy and was
      readministered during cadet orientation and during the stressful environment of
      Basic Cadet Training (BCT). Immune responsiveness was analyzed by PHA-, PMA-, or
      anti-CD3-stimulated thymidine uptake in mononuclear leucocytes. Illness episodes
      were assessed via medical chart review and self-reported symptoms. There were
      significant increases in distress levels as cadets entered BCT. No psychosocial
      measure assessed prior to arrival at the academy predicted level of PHA-, PMA-,
      and anti-CD3-stimulated thymidine uptake or risk of illness. However, hostility
      levels reported during BCT predicted risk of illness in the four weeks following
      psychosocial assessment (odds ratio = 7.1; 95% confidence interval: 1.4-36.1).
      Elevated response to environmental stressors and lower well-being levels also
      predicted impending illness, but only in the cohort of cadets who had not
      contracted food poisoning prior to assessment during BCT (OR = 9.3, CI = 1.9
      46.7; OR = 0.09, CI = 0.02-0.53). These results suggest that self-report measures
      of hostility, response to environmental stressors and well-being may be useful
      predictors of impending illness episodes in males encountering high stress
      environments.

PMID- 7562675
TI  - Perceived touch deprivation and body image: some observations among eating
      disordered and non-clinical subjects.
AB  - The developmental literature suggests that touch, consisting of secure holding
      and hugging, plays an important role in the formation of body image. We tested
      the hypothesis that women with anorexia nervosa and/or bulimia nervosa (N = 59),
      conditions associated with body image problems, report a greater deprivation of
      tactile nurturance than a sample of non-clinical randomly selected women (N =
      140) from the community. Measures of body image included the Drive for Thinness
      and Body Dissatisfaction subscales of the Eating Disorder Inventory. Perceived
      touch deprivation was rated on a 10-point scale, previously developed by the
      author. Analysis of covariance, controlling for the effects of age and body mass
      index, revealed that the eating disorder group reported greater (p < 0.0001) body
      image concerns and perceived greater (p < 0.0001) touch deprivation both during
      their childhood and their current life, than the non-clinical group. Our
      preliminary empirical findings suggest that touch deprivation may play a role in
      body image pathologies.

PMID- 7562676
TI  - Can psychological traits predict the outcome of lumbar disc surgery when
      anamnestic and physiological risk factors are controlled for? Results of a
      prospective cohort study.
AB  - In a prospective study 122 patients with herniated lumbar disc pre-operatively
      completed psychological questionnaires. Surgical outcome was evaluated 12 months
      post-operatively mainly by a composite clinical overall score (COS), and by its
      separate elements. Anxiety (HAD-A scale) and psychosomatic symptoms (MSPQ) had
      predictive value: fewer symptoms favoured a satisfactory overall outcome, and
      vice versa. The HAD-A Scale had a predictive power of poor (ppp) and satisfactory
      (pps) outcome of 28 and 81%, respectively. Correspondingly, for the MSPQ, the ppp
      and pps were 42 and 85%. Anamnestic and biological variables (including
      fibrinolytic variables: ECLT and PAI-1) predicted 20% of the outcome. By adding
      all psychological variables the prediction increased only to 24%, but the HAD-A
      Scale and the MSPQ were still significant. The results suggest that in order to
      further improve prediction of outcome, future studies should combine biological
      variables sensitive to the mental state of the patient, with psychometric
      assessments.

PMID- 7562678
TI  - Accurate awareness of heartbeat in hypochondriacal and non-hypochondriacal
      patients.
AB  - We measured the accurate awareness of resting heartbeat in a sample of medical
      out-patients meeting DSM-III-R criteria for hypochondriasis (n = 60), and in a
      comparison group of non-hypochondriacal patients (n = 60) from the same general
      medical clinic. Patients also completed subjective self-report ratings of their
      sensitivity to benign bodily sensation and of functional somatic symptoms.
      Hypochondriacal patients did not differ significantly from non-hypochondriacal
      patients in their accurate awareness of heartbeat. They did, however, consider
      themselves more sensitive to benign bodily sensation and report more functional
      somatic symptoms. Within each sample, the only statistically significant
      association found was a negative correlation (r = -0.32, p = 0.025) between
      heartbeat awareness and the severity of hypochondriacal symptoms among the
      hypochondriacal patients. These results suggest that hypochondriacs may not be
      more accurately aware of normal cardiac activity, and therefore that
      hypochondriacal somatic complaints may not result from an unusually fine
      discriminative ability to detect normal physiological sensations that non
      hypochondriacal individuals do not perceive.

PMID- 7562677
TI  - Genetic and environmental factors in premenstrual symptom reporting and its
      relationship to depression and a general neuroticism trait.
AB  - Previous work has indicated a genetic contribution to premenstrual symptom
      reporting, regularity and menarche but no genetic contribution to cycle length,
      and no consistent genetic contribution to premenstrual symptom reporting. This
      paper reports the results (n = 634) of multivariate genetic analysis in which
      premenstrual symptom reporting is included in a general personality factor along
      with extroversion (E), neuroticism (N) and depression (D). The results showed
      that N, E, D and PMS all fitted on a common personality factor. There was no
      evidence for a specific genetic contribution of depression or premenstrual
      symptom reporting over and above those shown in the common personality factor.
      There were, however, unique/specific environmental contributions for PMS. For E
      and N, in contrast, both unique genetic and environmental contributions were
      apparent.

PMID- 7562680
TI  - Life events and the onset of rheumatoid arthritis.

PMID- 7562679
TI  - Characteristics of individuals who excrete versus retain sodium under stress.
AB  - To examine the role of stress on renal sodium excretion, we studied 27
      normotensive and 21 hypertensive subjects. All subjects were placed on a
      standardized sodium diet. After water loading (2290 ml in 3 1/2 hr) they
      completed a 30 min baseline and a 30 min stress period (competitive videogame).
      Sixty-nine percent of the subjects increased ("excreters") and 31% decreased
      ("retainers") their sodium excretion under stress. In addition to increased
      potassium excretion (p < 0.006), excreters also manifested less of a stress
      associated increase in systolic (p = 0.055) and diastolic (p = 0.040) blood
      pressure and showed greater expression of anger (p < 0.02) than retainers. The
      same subjects were also studied to determin the effects of angiotensin converting
      enzyme inhibition (captopril 25 mg b.i.d.) on sodium excretion. On captopril,
      excreters now showed a retention of sodium (p < 0.001) and potassium (p < 0.01)
      under stress and no longer differed significantly in blood pressure reactivity.
      The results suggest that there are two different stress-related patterns of renal
      sodium excretion, that these patterns are related to blood pressure responses to
      stress, and may be related to anger expression. In addition, sodium excretion
      patterns under stress may be altered with certain type of antihypertensive
      medications.

PMID- 7562681
TI  - Trauma junkie: taking charge of my survival.
AB  - 1. Nurses face the threat of violence daily. 2. Awareness of your individual
      responses to violent behavior may help you survive a critical incident. 3.
      Deliberately enrich and balance your personal, work, and spiritual life to
      enhance both your quality of life and your ability to resist the negative effects
      of stress.

PMID- 7562682
TI  - Better late than never: of reminiscence and resolution.
AB  - My purpose in writing this article was to offer observations and helping
      strategies to nurse-colleagues who deal with depressed elderly. The process
      begins (as always) with careful assessment and a willingness to adapt strategies
      to changing needs. Change is expected--both in assessment data and in clients'
      behavior. This model is client-driven. The client defines her needs, her goals,
      her feelings, and her solutions. When the nurse offers suggestions, it is only to
      "prime the pump." The nurse must have no vested interest in the ultimate use of
      those suggestions. In fact, there is cause to rejoice when a client discards them
      in favor of her own. The nurse must avoid being cast in the role of referee or
      judge in working with Angry Depressed clients. Who is "to blame" in clients'
      ruptures with the family and/or friends is outside the nurse's area of concern.
      The focus is on healing those ruptures if the client wishes to do so and for the
      client's sake. Within the framework of Erikson's eighth stage, the client's task
      has been to resolve the tension between the polar extremes of integrity and
      despair. The tools at hand for accomplishing this task have been the client's
      intrinsic strengths and the nurse's professional skills. "Dorothy" and "Julia"
      have had some degree of success in this endeavor, placing them at positions
      closer to integrity on an integrity-despair continuum. Others have had less
      positive resolutions. Still others are "in process." One woman in her 80s has
      resumed telephone contact with her daughter after a long hiatus, but is still
      estranged from her son.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562683
TI  - Restraints: retraumatization for rape victims?
AB  - Clients who have experienced trauma through rape or sexual assault discuss the
      traumatic feelings associated with being placed in leather restraints during
      times of hospitalization for psychiatric/mental health problems. In the eyes of
      those who have openly discussed their private interpretations of their
      experiences, restraint becomes revictimization. The clients who came forward to
      tell their stories may be only a small percentage, or they may represent a much
      larger percentage of the inpatient psychiatric population than nurses and
      therapists have recognized. Developing a therapeutic rapport with clients is a
      critical element of psychiatric/mental health nursing that may be severely
      impaired if the client perceives nurses to be perpetrators of violence.

PMID- 7562684
TI  - Massage for the seriously mentally ill.
AB  - 1. Some seriously mentally ill clients have unfulfilled needs for safe touch. 2.
      Flashbacks or provocative behavior have not been triggered by the use of massage
      in a structured setting. 3. The blending psychiatric skills and therapeutic
      massage can be an effective stress reducer for inpatients or outpatients who seek
      safe touch.

PMID- 7562685
TI  - Therapeutic insight: from family to practice.
AB  - 1. Because of the positive and negative therapeutic insights gained by mental
      health professionals who have family members suffering from mental illness, an
      ongoing evaluation of one's practice must be balanced with careful introspection.
      2. Therapeutic insights that may be gained from family experiences include
      letting go of the shame; remembering the particular strengths in the psychiatric
      nursing role; knowing when you have regressed; learning when to get support; and
      learning to appreciate your talents as a mental health professional. 3. Mental
      health professionals who have family experiences with mental illness may bring a
      bias or suffer from countertransference; however, these individuals bring to work
      a unique perspective that is born from shared suffering and shared hope.

PMID- 7562686
TI  - Stimulating research thinking: the case for mini-research.
AB  - 1. Nursing faculty of Tel Aviv University developed a tool to improve care in
      geropsychiatric units. This resulted in the establishment of a national "forum"
      of geropsychiatric nurse practitioners, administrators, and educators. The forum
      conducts study days, publishes a journal, and encourages research activities. 2.
      A major achievement of the forum was the organization of more than 15 mini
      research groups of grass-roots nurses guided by an academic adviser. The groups
      examined nursing interventions, such as dolls as therapy, and specific patient
      care problems, such as violence, interpersonal relationships among patients, and
      needs of families. 3. The meetings and mini-research have had a positive impact
      on quality of patient care, increased family involvement, enhanced self-image of
      personnel, new ways of thinking, and a model for cooperation between service and
      academia.

PMID- 7562687
TI  - Susan.

PMID- 7562689
TI  - ATLS--essential training for Naval medical officers? Advanced Trauma Life
      Support.

PMID- 7562690
TI  - Telemedicine--a paramedical and specialist tool.

PMID- 7562688
TI  - Interviewing the young child sexual abuse victim.
AB  - 1. Nurses can facilitate the disclosure by a young child of sexual abuse by using
      developmentally sensitive language, such as through the use of proper nouns,
      single-idea sentences, and the avoidance of technical terms. 2. Nurses can guide
      the interview from benign, open-ended questions to context-specific, focused
      questions. Differentiation is made between being specific versus being
      suggestive. 3. Rapport-building is an important part of the alliance with the
      child and the nurse. Interviewers should be matter-of-fact and acknowledge any
      discomfort the child may demonstrate. 4. Cognitive interviewing is a specific
      technique designed to access accurate recall of a child's memories through
      reconstruction and memory-jogging techniques.

PMID- 7562691
TI  - Preparing to travel.

PMID- 7562692
TI  - A tropical experience.

PMID- 7562693
TI  - Case report: brucella osteomyelitis--a difficult diagnosis.
AB  - The patient in this case report was probably infected by ingesting unpasteurised
      milk from a non-immunised dairy herd. The initial infection which probably
      occurred some 10 years prior to presentation, was evident only by night sweats. A
      high index of suspicion must be maintained in patients complaining on non
      specific symptoms who are or have been at occupational risk, or have travelled in
      endemic areas of the world.

PMID- 7562694
TI  - The diagnosis, progression, prognostic indication and classification of
      periodontal disease: a review (Part 3).
AB  - Periodontal disease may be largely divided into gingivitis and periodontitis
      depending on the extent of tissue involved. It is not inevitable that all sites
      or patients exhibiting gingivitis will progress to periodontitis although it is
      rare for the latter to arise de novo. Although periodontal diseases frequently
      occur in the systemically healthy individual, systemic disease often modifies the
      response of these tissues and may offer an early chance to diagnose any
      underlying general health problems. A detailed full mouth periodontal examination
      must constitute part of the dental examination and can prove a valuable health
      screening measure as part of general health care.

PMID- 7562695
TI  - Is perianal sepsis adequately managed? The results of a five year audit at Royal
      Naval Hospital Haslar.
AB  - A retrospective audit and postal questionnaire of 148 patients presenting with
      perianal sepsis confirms that the isolation of gut-related organisms remains a
      sensitive indicator of a perianal fistula. It did not confirm that the use of
      microbiological results affects the long term outcome for these patients. It
      suggests that early examination under anaesthetic and laying open of a fistula
      may not be necessary in all patients in which gut-related organisms are
      identified. There was no statistical difference in recurrence rates of perianal
      sepsis between those operated on by senior or junior surgeons, though there may
      have been selection bias in these patients.

PMID- 7562696
TI  - Update on pre-registration nurse education.

PMID- 7562697
TI  - The Mary Rose and Tudor surgery.

PMID- 7562698
TI  - Nelson's wounds.

PMID- 7562699
TI  - Medical confidentiality in the Armed Forces.
AB  - The doctor/patient relationship is unique. The doctor's surgery/clinic can be
      likened to the confessional and the duty of confidence to a patient does not end
      with the patient's death. It is ongoing. It is accepted that in the Armed Forces,
      a Commanding Officer can request disclosure of all relevant medical information
      by his medical officer. The medical officer in this case would need to be guided
      not only by military law but also by guidelines laid down by the General Medical
      Council (the GMC 'blue book'). Each case needs to be considered on its own merit.
      The Medical Defence Union is available to discuss individual cases with its
      members. (An MDU booklet 'Confidentiality' is available free to members.
      Application may be made to the Medical Defence Union, 3 Devonshire Place, London
      W1N 2EA.)

PMID- 7562700
TI  - Radio medical advice--the Danish experience.
AB  - From 1980 to 1993, the Danish Radio Medical Advice Service (RMAS) had 1136
      contacts from overseas Danish merchant ships and 213 contacts from Danish
      territorial waters. The diagnoses were almost always of acute conditions. The
      distribution of the diagnoses in the overseas contacts were; diseases in the
      digestive and genitourinary system 30%, traumatic lesions 23%, infectious
      diseases 14% and diseases in the cardiovascular and respiratory system 9%. The
      only trend over the years was a significant (P = 0.01) decrease in psychiatric
      diagnosis. Evacuation from the ship was recommended in 53% and medicine was
      prescribed in 61% of the contacts. The medicine was antibiotics in 40% and
      analgesics in 29% of the contacts. Intravenous infusion was evaluated as relevant
      in 5% of the cases and this procedure will be included in the new education of
      officers on the ships. In the contacts from Danish territorial waters, where many
      ships are recreational yachts, evacuation was recommended in 79% and medicine was
      prescribed in 28% of the contacts. This was probably due to the short distance to
      the nearest harbour and the variation in medical equipment and knowledge. The
      medical speciality for doctors participating in RMAS should be general surgery or
      orthopaedic surgery but access to advice from all other medical specialities
      should be available. Experience as a naval medical officer would be beneficial.
      The education of the officers on the ships should be more comprehensive including
      e.g. intravenous infusion. Communication should be by telephone and television
      would be an advantage.

PMID- 7562701
TI  - Colorectal cancer in the Royal Navy--an opportunity to intervene?
AB  - Colorectal cancer is uncommon in Royal Naval personnel; an average of two cases
      are diagnosed annually, often with disease advanced at presentation. During the
      next five years, 10 serving individuals are likely to present with colorectal
      cancer and many, if not all of these, already harbour premalignant adenomas or
      asymptomatic colonic malignancy. Currently over 2,000 servicemen are estimated to
      carry undiagnosed colorectal adenomas. Requests for hospital appointments for
      those reporting a family history of colorectal cancer and who request screening
      are increasing in frequency. An understanding of the personal implications of a
      family history of colorectal cancer and a basis for the management of these
      individuals will be provided. This paper considers ways in which the impact of
      colorectal cancer on the Royal Navy and its pensioners could be altered. Evidence
      derived from population based and family history based colorectal cancer
      screening studies are organised into a protocol by which the Royal Navy might be
      examined. The effect of a family history of colorectal cancer on disease
      incidence and the percentage of positives resulting from faecal occult blood
      testing are applied to the age profile of the Royal Navy. These show that a
      maximum of 56 flexible sigmoidoscopies and 90 colonoscopies would be needed in
      the first year of a programme to attempt the early detection of colorectal
      neoplasia. This paper is aimed at gaining feedback from primary and secondary
      care practitioners so that the possibility of introducing a programme for the
      early detection of colorectal cancer in the Royal Navy can be considered.

PMID- 7562702
TI  - Cardiac diseases of young people. II: Hypertrophic cardiomyopathy.
AB  - HCM is an uncommon but serious disease with important implications in the
      services. It requires extensive evaluation and careful consideration of measures
      to reduce the risk of sudden death or deterioration to end stage heart failure.
      This can be achieved only by cardiologists with access to non-invasive and
      invasive testing facilities and with reference to colleagues with wide experience
      of the condition. It has been suggested that in those identified to be at high
      risk of sudden death, appropriate therapeutic measures including drug and pacing
      therapy may allow a return to strenuous activity. These findings are preliminary,
      involving small numbers of patients and are unlikely to be acceptable in a
      service environment. HCM should be a bar to entry into the services but if the
      diagnosis is made during active service it may be compatible with limited
      continued service following full evaluation including an assessment of risk of
      sudden death.

PMID- 7562703
TI  - Tuberculous epididymitis presenting as acute hydrocele.
AB  - A case of tuberculous epididymitis which presented as an acute hydrocele is
      reported and the relevant literature reviewed. The patient had undergone
      contralateral orchidectomy 20 years previously for the same condition associated
      with pulmonary tuberculosis. The most recent episode followed unrelated illness;
      the diagnosis was confirmed after surgical intervention and cure was achieved
      with adjuvant chemotherapy. Although rare, genital tuberculosis should still be
      considered in cases of scrotal swelling when there is a history of previous
      tuberculous disease or exposure.

PMID- 7562704
TI  - Penile problems--hidden lesions of the sailor.

PMID- 7562705
TI  - Orthopaedic implant removal at Royal Naval Hospital Stonehouse: a three-year
      review.
AB  - A recent study stated that 11% of all elective orthopaedic procedures performed
      at a Regional Orthopaedic Unit involved removal of orthopaedic implants.
      Indications for certain orthopaedic implant removal remain unclear. As budgets
      are squeezed even tighter throughout all branches of the Royal Navy, we looked at
      each operation performed for orthopaedic implant removal at Royal Naval Hospital
      Stonehouse and questioned their effectiveness with respect to finance and working
      days lost for serving personnel.

PMID- 7562706
TI  - The early morbidity of varicose vein surgery.
AB  - The early outcome and morbidity associated with varicose vein surgery were
      assessed at six months post operation by postal questionnaire. Most cases
      underwent sapheno-femoral ligation, above-knee stripping of the long saphenous
      vein and multiple stab avulsions. A 73.8% response rate resulted in 155 replies,
      and revealed a high incidence (65.8%) of perceived complications within the first
      two weeks after surgery. The commonest of these were bruising, pain and numbness.
      Over a third of patients consulted their general practitioner (GP)
      postoperatively. Half of these required further management or treatment and the
      rest, reassurance alone. At six months 79.4% were satisfied with the outcome of
      their surgery, although some still claimed problems with residual veins, skin
      discoloration, numbness, and ankle or foot discoloration. Eleven percent were
      referred to hospital for further opinion, mostly because of perceived residual
      varicose veins. The difference between residual and recurrent varicose veins is
      discussed. No patient felt that the standard 2.5 day admission was too long, and
      12.9% thought it too short. Day case surgery is not a popular option in this
      population group. Despite high satisfaction rates, there is a considerable
      morbidity attached to varicose vein surgery. We believe that good pre- and
      perioperative communication, augmented by a comprehensive information sheet, is
      important to prepare patients for those postoperative problems and thus reduces
      their perceived importance.

PMID- 7562707
TI  - A year of laparoscopic general surgery at RNH Haslar.
AB  - Laparoscopic general surgery at RNH Haslar started in October 1992. A review of
      the procedures undertaken in the first year (October 1992-October 1993) and
      comparison with some published series is presented.

PMID- 7562708
TI  - Shipshape and Bristol fashion: a personal view of higher professional training in
      Bristol University, Department of Surgery.

PMID- 7562709
TI  - Learning in the clinical area: the Portsmouth Partnership experience.
AB  - This paper outlines a new, innovative method of obtaining a degree pertinent to
      one's job description. The Partnership Programme implemented from the University
      of Portsmouth had its first intake of students in October 1992. The course is
      primarily aimed for students in full-time employment. Following submission of a
      portfolio, students can obtain a degree in two years. Students undertake part
      time university modules and learning projects at the workplace, the latter
      forming up to 60% of their total credits. Presently there are only two similar
      course frameworks in the United Kingdom.

PMID- 7562710
TI  - Pitfalls in Accident and Emergency Departments.

PMID- 7562711
TI  - Consent to treatment.

PMID- 7562712
TI  - The Royal Naval Medical Branch ratings and Sick Berth Staff Association.

PMID- 7562713
TI  - Tuberculosis in the Royal Navy.

PMID- 7562714
TI  - Skin paddle salvage in the fibula osteocutaneous free flap with secondary skin
      paddle vascular anastomosis.
AB  - The fibular osteocutaneous free flap has become a popular choice for the
      reconstruction of bone and skin defects. A potential drawback has been the
      reported unreliability of the skin paddle. Previous studies have emphasized total
      loss of the overlying skin paddle, if the expected perforating vessels are not
      present either in the intermuscular septum or in the soleus. Two cases are
      presented in which the skin paddle was found to be supplied by vessels arising
      from the proximal peroneal artery. there were no intraseptal or intramuscular
      vessels in the osteocutaneous septum which connected to the overlying skin
      paddle. The skin island was salvaged by performing independent microsurgical
      anastomoses of the fibular graft and the skin paddle. Both patients had complete
      survival of the fibula and overlying skin paddle.

PMID- 7562715
TI  - Entire scalp replantation: case report and review of the literature.
AB  - A case of successful replantation of a totally avulsed scalp in a 40-year-old
      woman is presented. During a 19-hr surgical procedure, bilateral superficial
      temporal arteries and veins were anastomosed. The postoperative course was
      uneventful, except for partial necrosis of the distal end of the avulsed flap,
      i.e., the occipital region. Since the first successful scalp replantation using
      microsurgical technique was reported in 1976, the authors have found at least 32
      subsequently reported cases. Of these, there were 22 cases of entire scalp
      avulsion (more than 80 percent of the scalp), including 15 females and seven
      males. A summary of these cases is included. From analysis of the reported cases
      of entire scalp avulsion, the keys to success in scalp replantation are
      considered to be the adequate selection of vessels for repair and the use of vein
      grafts, if necessary.

PMID- 7562716
TI  - Split, free, jejunal transfer for pharyngoesophageal and soft-tissue
      reconstruction.
AB  - Pharyngoesophageal reconstruction utilizing free jejunal transfer is well
      established. Extensive resection or debridement for extensive tumor, infection,
      or radiation may necessitate additional soft-tissue coverage. The authors report
      a successful reconstruction using a split, free, jejunal transfer to provide
      simultaneous pharyngoesophageal and soft-tissue coverage.

PMID- 7562717
TI  - "Plasmatic imbibition" in the rabbit flow-through venous flap, using horseradish
      peroxidase and fluorescein.
AB  - In the present study, the phenomenon of "plasmatic imbibition" was investigated
      histologically in a rabbit flow-through venous flap model, using horseradish
      peroxidase and fluorescein. Horseradish peroxidase introduced between the flap
      and the recipient bed, produced brown staining of the entire contact surface 10
      min postoperatively. At 30 min, erythrocytes in the flow-through vein stained
      red. The flap and the erythrocytes became more intensely stained over time. When
      horseradish peroxidase was introduced from a central artery after a Silastic
      sheet had been inserted between the flap and recipient bed, the flap color became
      a soft brown and the erythrocytes of the flow-through vein stained red 10 min
      postoperatively. In the experimental groups subjected to fluorescein, introduced
      between the graft (or flap) and the recipient bed, fluorescence was seen 10 min
      postoperatively, except in the flow-through vein. At 30 and 120 min, the whole
      graft (or flap) showed fluorescence. Fluorescein was introduced into the femoral
      vein after flap elevation, or a Silastic sheet was inserted between the flap and
      the recipient bed. At 10 min, these groups showed a weak fluorescence only in the
      flow-through vein; subsequently, at 120 min, the flow-through vein and its
      surrounding tissue showed fluorescence, but the flap showed none. Plasmatic
      imbibition was proved to be acting in the flow-through vein, and it is considered
      as important a phenomenon in flap survival as venous flow itself.

PMID- 7562718
TI  - Variations in the vascular pedicle of the rat gracilis muscle flap.
AB  - The rat gracilis muscle is a reliable model for microsurgical research.
      Exploration of 364 inguinal regions and preparation of 80 free gracilis muscle
      flaps in Sprague-Dawley and Lewis rats revealed six distinct origins of the
      dominant arterial pedicle and four variations of the venous pedicle. Popliteal,
      external iliac, and truncus pudendoepigastricus associations are described for
      the first time in this study. The total incidence of atypical variation of
      arterial pedicle origin is 20.7 percent. The most common origin of muscular
      branch arteries are the superficial epigastric artery (53.3 percent), femoral
      artery (22.0 percent), popliteal artery (14.6 percent), and the external iliac
      arteries (5.5 percent). Muscular branch veins drain most frequently into the
      femoral vein (79.1 percent). Gracilis muscle flaps prepared from rats weighing
      329 +/- 45 g weighed an average of 0.64 +/- 0.13 g, and their volume averaged
      0.87 +/- 0.12 ml. Muscular branch artery and vein diameters (external) averaged
      0.21 +/- 0.05 mm and 0.54 +/- 0.06 mm, respectively. This new anatomic
      information is essential for reproducible microsurgery research using the rat
      gracilis muscle.

PMID- 7562719
TI  - The scalene reflex: relationship between increased median or ulnar nerve pressure
      and scalene muscle activity.
AB  - Neck pain, headaches, upper thoracic pain, and dystonic scalene muscles are
      common findings in patients who have severe entrapment neuropathies of the upper
      extremities. This problem was taken to the laboratory in an attempt to discover
      the correlation between distal entrapment neuropathies, brachial plexus
      entrapments, and prominent scalenus muscles. When increased pressure (over 40
      mmHg) was applied to the median and ulnar nerves in the forelimbs of eight goats,
      increased electromyographic activity was noted in the ipsilateral scalenus
      muscle. Pressures ranging from 100 to 150 mmHg caused increased electromyographic
      activity on the contralateral scalene muscle, and the authors postulate that it
      is mediated by the gamma afferent and efferent system. This relationship may
      explain the commonly found neck pain and muscle spasm in patients with peripheral
      neuropathies, and it represents a link between the somatic efferent nerves and
      the gamma motor neuron system. At present, the same phenomenon has been
      documented in 30 humans with the diagnosis of brachial plexus entrapment.

PMID- 7562721
TI  - A fixed anastomotic coupling device.

PMID- 7562720
TI  - Levator scapulae transfer and fascia lata fasciodesis for chronic spinal
      accessory nerve palsy.
AB  - A retrospective evaluation of the functional results after reconstructive
      treatment with levator scapulae transfer and scapulo-spinal fasciodesis by fascia
      lata slings for complete chronic trapezius palsy is presented. Five patients
      (ages 6 to 40 years) were operated on between 1988 and 1991 because of
      incapacitating pain and/or functional limitations. Treatment was recommended
      after failure to alleviate symptoms by a shoulder-girdle muscle-strengthening
      program or after unsuccessful nerve graft. The descriptions of the results are
      drawn from the last follow-up evaluation available for each patient (minimum: 14
      months post-operative). They are expressed in terms of functional recovery,
      residual pain, and patient satisfaction. Three patients had an excellent result,
      with at least 80 percent of normal abduction and forward elevation of the arm, no
      residual pain, and a high satisfaction rate. One patient showed good improvement
      in function, with 90 percent of normal shoulder function, but complained of some
      residual pain. The last patient was not improved by the surgery. Levator scapulae
      transfer and scapulo-spinal fasciodesis by fascia lata slings, substitute for the
      function of the upper trapezius and enhance the function of the serratus
      anterior, thus helping to relieve pain and to improve shoulder function after
      chronic trapezius palsy. The procedure warrants consideration in patients who are
      not candidates for nerve repair and reconstruction.

PMID- 7562722
TI  - Peripheral nerve surgery today, turning point or continuous development? Part
      VII. Vienna, Austria, November 23-26, 1991.

PMID- 7562723
TI  - Rethinking dental insurance.

PMID- 7562724
TI  - Smoking and oral health: a population survey in Finland.
AB  - OBJECTIVES: A survey was conducted to study smokers' oral health behaviors and
      attitudes, and to determine if smokers were advised by their dentists to quit
      smoking. METHODS: A random sample of 1,200 adults 15 to 64 years of age living in
      the province of North Karelia, Finland, was selected in each of two study years
      (1990 and 1991) and surveyed using a mail questionnaire. The 102-item
      questionnaire solicited information on smoking status, oral health behaviors,
      missing teeth, perceptions of tobacco's harmful effects on oral health, smoking
      status and quitting, and advice on smoking cessation provided by dentists.
      Variations in behaviors and opinions according to smoking status were analyzed.
      RESULTS: Nonsmokers reported more frequent healthy oral health behaviors than did
      daily smokers, with the exception that no difference in toothbrushing frequencies
      existed among women. Daily smoking was associated with increased use of sugar in
      tea or coffee, and with more frequent alcohol consumption. Daily smoking was
      correlated with the number of missing teeth in bivariate analyses, but not in
      multivariate analyses. Fewer daily smokers than nonsmokers considered smoking to
      have harmful effects on oral health. The majority of daily smokers, however,
      wanted to quit. Eight percent of daily smokers reported that they had been
      advised by their dentist to quit. CONCLUSIONS: Dentists need to provide patients
      with counseling on tobacco use because of the desire of many smokers to quit.
      Counseling of smokers by the oral health team requires special attention and
      skills, because smokers' health behaviors and attitudes appear to be less
      favorable to oral health compared to nonsmokers.

PMID- 7562726
TI  - Oral cavity and pharyngeal cancer among Department of Veterans Affairs hospital
      discharges.
AB  - OBJECTIVES: The purpose of this study is to determine the number of oral cavity
      and pharyngeal cancers among hospital discharges at Department of Veterans
      Affairs (VA) medical centers in one 12-month period. METHODS: A SAS file was
      created from the patient treatment file (PTF) with all discharges during fiscal
      1990 having ICD-9-CM codes for oral cavity and pharyngeal cancer. Up to 10
      discharge diagnoses from the most recent discharge summary were included in the
      data set. ICD-9-CM codes for alcohol dependence syndrome, drug dependence, and
      nondependent abuse of drugs also were included. ICD-9-CM codes for salivary and
      nasopharyngeal cancers were excluded. RESULTS: There were 3,733 unique
      individuals discharged with a diagnosis of oral cavity and pharyngeal cancer. The
      majority of cases (62%) were found in the oral cavity. The age distribution of
      oral cavity and pharyngeal cancer did not parallel the age distribution of
      veterans discharged during this year. Race and ethnicity of those discharged with
      the disease does not differ from that of all VA hospital discharges for 1990.
      CONCLUSIONS: VA data provide descriptive statistics of oral cavity and pharyngeal
      cancer among VA hospital discharges. VA data sets such as the PTF may offer the
      opportunity to examine hospital management issues, length of stay, and co-morbid
      diagnoses associated with oral cavity and pharyngeal cancer.

PMID- 7562725
TI  - Attitudes of college football coaches regarding NCAA mouthguard regulations and
      player compliance.
AB  - OBJECTIVES: The purpose of this study was to assess the attitudes of Division 1-A
      college head football coaches regarding the NCAA mouthguard regulations, current
      patterns of use by players, and responsibility for enforcement; and to compare
      the coaches' responses with those of officials studied previously. METHODS: A 15
      item questionnaire was mailed to all 106 Division 1-A football coaches to assess
      their attitudes. Percent frequency distributions of coaches' responses to each
      item were computed and compared to the officials' responses. RESULTS: Responses
      were received from 98 coaches (92.45%). While 87 percent of coaches reported
      having a team dentist, the majority reported that the team trainer was
      responsible for selecting the type of mouthguard used. Most coaches (53%)
      reported that all players wore mouthguards, but that quarterbacks were least
      compliant. Most coaches reported that mouthguard rules were beneficial in
      determining player compliance and resulted in more frequent use. Seventy-four
      percent would warn the player of a violation themselves, yet only 26 percent felt
      the coach had the greatest influence on players wearing mouthguards. Seventy-six
      percent felt the current enforcement of the rules is appropriate. Coaches
      opinions varied from those of officials. CONCLUSIONS: Coaches view themselves,
      the players, or the trainer as most responsible for players wearing mouthguards,
      not referees. This finding coincides with the officials' opinion that the coaches
      should be accountable.

PMID- 7562727
TI  - Longitudinal evaluation of sealing molars with and without incipient dental
      caries in a public health program.
AB  - OBJECTIVES: This study undertook a retrospective evaluation of the effect of
      sealants on the caries experience of initially sound and incipient permanent
      first molar pit and fissure surfaces. METHODS: Records of children with complete
      five-year records were obtained from a school-based dental sealant program in a
      fluoridated community. Sealants were placed on 677 tooth surfaces in 96 children;
      120 tooth surfaces in 17 children who received baseline examinations were not
      sealed because of lack of caregiver consent. Tooth surfaces were initially
      diagnosed as being sound or having incipient lesions, and evaluated for caries
      status after five years. RESULTS: For initially incipient surfaces the five-year
      decay rate was 10.8 percent (41 of 380 surfaces) for sealed surfaces and 51.8
      percent (29 of 56 surfaces) for nonsealed surfaces with an odds ratio of 8.88
      (95% CI = 4.56, 17.35). Initially sound surfaces had a decay rate of 8.1 percent
      (24 of 297 surfaces) for sealed surfaces and 12.5 percent (8 of 64 surfaces) for
      nonsealed surfaces with an odds ratio of 1.63 (95% CI = 0.63, 4.08). The two odds
      ratios were significantly different. CONCLUSIONS: Initially sound tooth surfaces
      were unlikely to become decayed in five years, and did not benefit greatly from
      the application of sealants. Within the limitations of this study, there were
      clear efficiencies in sealing incipient, but not sound, surfaces. The targeting
      of teeth with incipient caries for sealants is therefore recommended.

PMID- 7562729
TI  - Fluoride supplement use by children in fluoridated communities.
AB  - OBJECTIVES: The purpose of this study is to describe patterns of inappropriate
      fluoride supplementation among a sample of Connecticut schoolchildren living in
      optimally fluoridated areas. METHODS: Fluoride exposure histories were obtained
      via a written questionnaire with a response rate of 89 percent and an overall
      reliability of 87 percent agreement. RESULTS: A total of 575 subjects lived the
      entire first eight years of life in a fluoridated community. Of these, 26.1
      percent had a history of inappropriate supplementation sometime during that
      period, including 31.8 percent of subjects with mild to moderate fluorosis and
      22.8 percent of subjects without fluorosis. There were no significant supplement
      history differences related to current age, sex, or socioeconomic status.
      Overall, 71 percent of these subjects used only vitamins with fluoride, while
      only 14 percent were reported to have used fluoride supplements alone. Sixty
      eight percent of the subjects who were supplemented while breast feeding,
      continued supplementation after cessation of breast feeding. CONCLUSIONS: These
      findings reinforce the need for health professionals to be targeted more
      aggressively at the school, residency, and private practice levels to better
      promote a full understanding of the proper utilization of fluoride supplements.

PMID- 7562728
TI  - Risk factors for dental fluorosis in pediatric dental patients.
AB  - OBJECTIVES: Concerns have been raised recently about whether a substantial amount
      of dental fluorosis is resulting from the increased use of fluoride from various
      sources. The purposes of this study were to determine the prevalence and severity
      of dental fluorosis in a sample of pediatric patients seeking dental treatment in
      a university pediatric dental clinic and to evaluate sources of fluoride as risk
      factors for dental fluorosis. METHODS: A convenience sample of 157 children aged
      8 to 17 years were examined for dental fluorosis using the Tooth Surface Index of
      Fluorosis (TSIF). Fluoride history questionnaires assessing previous exposure to
      fluoride during the first eight years of life were completed by the children's
      parents. Fluoride exposures were compared among 54 cases and 54 matched controls
      using a case-control retrospective design. RESULTS: Fluorosis was found in 72
      percent of the children, but was generally quite mild. The risk of fluorosis was
      significantly greater for children who had greater exposure to fluoridated water
      and who used larger amounts of fluoridated toothpaste up to age eight.
      CONCLUSIONS: This study provided evidence that increased use of fluoride
      toothpaste may be a risk factor for dental fluorosis. The results suggest prudent
      use of dentifrice by young children to minimize the risk of fluorosis.

PMID- 7562730
TI  - The prevalence of dental fluorosis in a school-based program of fluoride
      mouthrinsing, fluoride tablets, and both procedures combined.
AB  - OBJECTIVES: The objective of the study was to describe and compare the prevalence
      and severity of dental fluorosis in children who participated in an eight-year
      clinical trial of the effectiveness of school-based fluoride procedures according
      to three treatment regimens and age of regimen initiation. METHODS: At baseline
      in 1981, 1,640 kindergarten and first grade children residing in a fluoride
      deficient community (Springfield, OH) were assigned randomly to a group that (1)
      rinsed once a week with a 0.2 percent neutral NaF solution; (2) chewed, rinsed,
      and swallowed daily a neutral 2.2 mg NaF tablet; or (3) carried out both
      procedures. DMFS examinations were conducted at baseline and after two, five, and
      eight years of treatment. As a follow-up in 1992, fluorosis examinations using
      Dean's index were conducted on 448 remaining subjects. RESULTS: Overall, the
      prevalence of fluorosis was 4.4 percent with 20 children classified as having
      some definitive level of the condition. No statistically significant differences
      existed in the prevalence or severity of fluorosis: (1) among the preventive
      regimens; (2) among children who began the regimens at ages 5, 6, or 7; or (3) by
      eruptive status of teeth. CONCLUSION: These results reiterate the safety of
      school-based fluoride mouthrinse, fluoride tablet, or combined regimens in
      communities with fluoride-deficient water supplies.

PMID- 7562731
TI  - Enamel opacities and dental esthetics.
AB  - OBJECTIVES: The purpose of this study was to determine the esthetic importance of
      different types of developmental enamel defect. METHODS: In the first method
      used, individual subjects from three different populations with less than 0.1,
      0.7, and 0.9 ppm fluoride in their drinking water, were asked about the
      appearance of their teeth and results compared to assessments of clinical
      photographs made by a single examiner. In the second method used, dentist and lay
      observers were asked to assess the appearance of the dentition of selected
      individuals who had a range of enamel defects. RESULTS: According to the first
      method, both the size of demarcated opacities and the degree of enamel
      hypomineralization (TF index) were related to satisfaction with appearance.
      However, there was no difference in satisfaction with the appearance of the teeth
      among the three areas included in this study. In the second method, similar types
      of enamel defects were found to be esthetic stimuli as with the first study, but
      the dentists responded more strongly to the stimulus of enamel hypomineralization
      than the lay examiners. CONCLUSIONS: Both demarcated opacities and enamel
      hypomineralization may be important when assessing differences between
      populations. Further, esthetic ratings by dentists may not be a suitable means of
      assessing the esthetic importance of different types of enamel defects.

PMID- 7562732
TI  - Predetermination as a cost-containment mechanism in a social allowances dental
      program in Manitoba.
AB  - OBJECTIVES: A review of dental consultant actions during predetermination of
      benefits in the publicly insured indemnity program in Manitoba under which Social
      Allowances Health Services certificate holders receive dental care was undertaken
      to determine the value of this process as a cost-containment mechanism. METHODS:
      Dollar amounts of services denied by a dental consultant during eight
      predetermination sessions selected to represent the 96 sessions during the 1990
      91 fiscal year were determined and grouped according to category of service.
      RESULTS: Approximately one-third of average total expenditures each month were
      reviewed by the dental consultant through the predetermination process. Of the
      requested dollar amount reviewed, 26 percent was denied, a savings of 8.5 percent
      of average total monthly expenditures. The categories of services that made up
      the denied requests were: prosthodontics (30%); endodontics (32%); restorative
      (5%); periodontics (12%); and miscellaneous (21%), including diagnostic,
      surgical, preventive, orthodontic, and adjunctive. CONCLUSIONS: A properly
      administered predetermination process can save a third party 8.5 percent of total
      plan expenditures; dollar changes to altered treatment plans amount to a 26
      percent reduction of expenditures relating to these requests. A predetermination
      process with an unbiased appeal mechanism provides a system to advise and protect
      providers regarding what treatment is covered.

PMID- 7562733
TI  - Variation in dentists' clinical decisions.
AB  - OBJECTIVES: The first comprehensive review of the recent literature regarding
      variation in dentists' clinical treatment decisions is presented. METHODS:
      Variation among dentists in the clinical decisions they make as well as the
      methods used for assessing this variation are examined at three levels of
      aggregation of clinical decisions: the dental practice (or dentist), the patient,
      and the individual tooth. RESULTS: The extent to which differences in dentists'
      clinical decisions have been examined is limited. Studies are particularly sparse
      at the level of the dental practice, where the aggregate of dentists' treatment
      decisions is reflected. Further, the methods and measures used to assess
      variation tend to be different across studies, making quantification of variation
      difficult. Nevertheless, the available information reflects substantial variation
      in measures such as rates of provision of specific procedures; cost and numbers
      of procedures recommended for specific patients; and diagnoses, intervention
      decisions, and treatment selections for individual teeth. CONCLUSIONS: Even when
      differences in patients are controlled, variation in dentists' clinical decisions
      is ubiquitous. While its consequences remain undetermined, the variation in basic
      clinical decisions such as caries diagnosis signals the need to consider the
      extent to which the appropriateness of care is affected.

PMID- 7562734
TI  - Metastatic squamous cell carcinoma of the hand and review of the literature.
AB  - New cases of cancer amongst medical workers arising as a result of X-ray exposure
      are now rare. We record a case of a dentist who presented 11 years ago with a
      radiation induced squamous cell carcinoma of the ring finger of his left hand
      with massive axillary lymphadenopathy. Repeated exposure of his hands to
      diagnostic dental irradiation in his surgery had lead 16 years previously to a
      troublesome radiodermatitis which had been mistakenly diagnosed and had itself
      been treated with radiotherapy without effect. Management by amputation of the
      distal phalanx of the ring finger, debulking of the axillary lymphadenopathy with
      adjunctive radiotherapy to the axilla and chemotherapy, have been successful in
      achieving a prolonged disease free interval and satisfactory hand function.

PMID- 7562735
TI  - Acute respiratory distress syndrome following autotransfusion with the Biosurge
      autotransfuser.
AB  - A case of acute respiratory distress syndrome in a 79-year-old man is presented
      in which the use of a BioSurge synchronous autotransfuser may be implicated. This
      has not been reported before.

PMID- 7562736
TI  - Reproductive performance on the Maltese Islands during the First World War.

PMID- 7562737
TI  - Chronic fatigue syndrome in Army general practice.

PMID- 7562738
TI  - Paradoxical bronchoconstriction with salbutamol.

PMID- 7562739
TI  - The Army and the Cochrane collaboration.

PMID- 7562741
TI  - Screening for ischaemic heart disease by maximal exercise testing as part of the
      extended PULHHEEMS examination--the first 10 years.
AB  - Exercise tests have been an integral part of the extended PULHHEEMS examination
      since its inception in 1983. In the first 10 years a total of 240 individuals
      have been examined and 180 (75%) have had normal exercise tests. Individuals with
      an abnormal test who wished further assessment (58) were subjected to an exercise
      thallium scan. Of these 36 were normal allowing reassurance of the individual. Of
      the 22 abnormal scans 15 were subjected to regular follow-up whilst 7 were
      sufficiently abnormal to merit angiography. Of the seven patients who had
      angiography one was normal, 3 had significant coronary artery disease and 3 had
      mitral valve prolapse.

PMID- 7562740
TI  - The Sir David Bruce Lecture, 1994. A matter of principles.

PMID- 7562742
TI  - Immunisation of armed service medical personnel against hepatitis B infection.
AB  - Clinical and laboratory staff of the Army and RAF medical services at risk of
      acquiring infection with hepatitis B were immunised against the virus with a
      recombinant vaccine. Vaccine was administered in Service hospitals and medical
      centres located throughout the world. After a primary course of vaccine, 73% of
      personnel developed anti-HBs titres > or = 100 IU/L to hepatitis B surface
      antigen and were considered protected; 11% were non-responders (anti-HBs < 10
      IU/l). A significantly higher proportion of females than males, and vaccinees
      under 40 years of age, produced a good response. Among those achieving a good
      response, antibody titres were higher in the younger age group and in females.
      After a fourth (booster) dose of vaccine, 87.2% of the poor responders and 37%
      non-responders, developed anti-HBs titres > or = 100 IU/L.

PMID- 7562744
TI  - Audit of asthma care in Army general practice.
AB  - Asthma is a common condition. General Practitioners in the NHS now receive
      specific remuneration for running asthma disease management programmes. This
      paper presents the results of an audit of asthma management in an Army General
      Practice. The records of all patients were reviewed. In addition a questionnaire
      survey of patient knowledge and satisfaction was undertaken. The study identified
      several areas for improvement.

PMID- 7562743
TI  - Do cadet force units need a dedicated medical pack?
AB  - There are over 38,000 army cadets in the United Kingdom of whom about 20,000
      attend a two week annual camp each summer. In response to criticisms from the
      medical staff attached to cadet units about the suitability of the routinely
      issued medical pack, a national questionnaire survey of all serving Army Cadet
      Force medical personnel has been performed, along with an analysis of patient
      attendances at annual camp between 1989 and 1992 in one East Midlands County
      Force. In particular the appropriateness of the Medical Treatment Pack Training
      Camp Large as currently issued to cadet units has been examined. The findings
      suggest that, on its own, the pack is unsuitable to treat about 40% of cadets who
      attend for medical treatment during annual camp; medical staff on average rate
      its suitability for cadets as very low. Moreover, there is objective evidence
      that most cadet units need to obtain extra medical supplies, particularly
      bronchodilators, modern antibiotics and modern dressings; many do so via private
      purchases from civilian sources. The study highlights a situation in urgent need
      of review.

PMID- 7562745
TI  - Perinatal death: worse obstetric and neonatal outcome in a subsequent pregnancy.
AB  - A retrospective case-control study was undertaken of women with a history of a
      previous stillbirth or neonatal death, who subsequently delivered in BMH Rinteln.
      Their obstetric and neonatal outcome was compared to that of a control group of
      women of similar age and parity and its relationship to specific socio-economic
      factors assessed. Index patients had a worse obstetric and neonatal outcome. They
      were statistically significantly more likely to be admitted to hospital during
      their pregnancy (46% vs 26%), to have medical complications (58% vs 34%), to be
      delivered prematurely (16% vs 8%), and by Caesarean section (22% vs 9%). Their
      babies were more likely to have complications (28.8% vs 20.4%), to be of low
      birth weight (14% vs 7%), require intubation (11% vs 5%) and be admitted to the
      Special Care Baby Unit (SCBU) (13% vs 7%). Apart from small stature, no
      differences in socio-economic factors between the two groups could be identified.
      Index patients were four times more likely than controls to have their pregnancy
      terminated prematurely as a result of complications (6.7% vs 1.6%), but there was
      also a high level of obstetric intervention in the absence of clear medical
      indications. Although perinatal mortality was not statistically increased, the
      results were suspicious and it is concluded that these women should continue to
      be considered a high-risk group.

PMID- 7562746
TI  - Noise induced hearing loss in military helicopter aircrew--a review of the
      evidence.
AB  - Noise Induced Hearing Loss (NIHL) has been recognised for some time. In the
      military environment one group of personnel at risk are Army helicopter aircrew
      who are exposed to continuous noise levels of up to 100 dB(A) in flight. The
      evidence for the damaging effect of this occupational noise is reviewed and some
      of the difficulties in drawing conclusions are highlighted. The current
      protection offered for the Mk 4 helmet is discussed and the incorporation of
      Active Noise Reduction (ANR) is suggested as a likely way of ensuring that the in
      flight noise exposure in Army aircrew is kept as low as possible.

PMID- 7562747
TI  - Measurement of skin involvement in scleroderma.

PMID- 7562748
TI  - Gene therapy and arthritis.

PMID- 7562749
TI  - Lipopolysaccharide binding protein as a marker of inflammation in synovial fluid
      of patients with arthritis: correlation with interleukin 6 and C-reactive
      protein.
AB  - OBJECTIVE: To determine levels of lipopolysaccharide binding protein (LBP) in
      serum and in synovial fluid (SF) of patients presenting with various articular
      disorders [degenerative arthritis, rheumatoid arthritis (RA), reactive arthritis
      (ReA)] and to correlate these levels with C-reactive protein (CRP) and
      interleukin 6 (IL-6), 2 markers of the acute phase response. METHODS: LBP was
      measured by a radioimmunoassay made up of lipopolysaccharide (LPS) to capture LBP
      and radiolabelled anti-LBP antibodies to detect LBP. LBP was also measured for
      its ability to present fluorescein isothiocyanate LPS (FITC-LPS) to human
      monocytes. CRP was measured by nephelometry and IL-6 bioassay. RESULTS: Levels of
      LBP in serum and in SF were significantly higher in patients with RA and ReA than
      in the control group of degenerative arthropathies. In the latter group, LBP
      values were similar to those found in controls. Serum LBP values correlated
      positively with SF LBP values. LBP values also correlated with CRP and IL-6
      levels measured in SF. Functionally, LBP was found to be active and able to
      present LPS to monocytes, resulting in tumor necrosis factor-alpha (TNF-alpha)
      release upon LPS challenge. CONCLUSION: These in vitro data support the
      observation that LBP could play a major role in local joint disorders. Our
      results also strengthen the view that LBP may be a new marker of synovial
      inflammation.

PMID- 7562750
TI  - High levels of antibodies to annexins V and VI in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Glucocorticoids are powerful antiinflammatory agents widely used for
      the treatment of rheumatoid arthritis (RA). Synthesis and/or secretion of annexin
      I (A-I) is induced by these steroids. Annexins V and VI are also found
      extracellularly but are not induced by glucocorticoids. Annexins may be potent
      antagonists of phospholipase A2 (PLA2). Since autoantibodies to A-I have been
      reported in patients with RA, we studied the reactivity of sera from patients
      with RA to A-V and A-VI. METHODS: Sera from 26 patients with RA were assessed for
      anti-A-V and anti-A-VI antibodies and compared with sera from 26 sex/age matched
      healthy subjects. IgG and IgM antibodies were analyzed in an ELISA: A correlation
      study with disease activity and corticosteroid treatment schedule was performed.
      RESULTS: Sera from patients with RA contained significantly higher levels of IgG
      [anti-A-V and anti-A-VI] autoantibodies than control sera, both being correlated.
      This rise in antiannexin antibody titers was correlated with the RA activity
      score, and negatively correlated with the daily dose of corticosteroids.
      CONCLUSION: High levels of IgG (anti-A-V and anti-A-VI) antibodies were found in
      sera from patients with RA. We suggest that antiannexin autoantibodies may play a
      role in the clinical course of RA by impairing the anti-PLA2 effect of annexins.

PMID- 7562752
TI  - Percentile curve reference charts of physical function: rheumatoid arthritis
      population.
AB  - OBJECTIVE: To construct percentile curve reference charts of physical function in
      a population of patients with rheumatoid arthritis (RA); to explore the
      relationship of age, gender, and disease duration on physical function using
      percentile curve reference charts; to explore the potential clinical applications
      of percentile curve reference charts. METHODS: We surveyed 358 patients with RA
      from a teaching hospital clinic and 4 rheumatological private practices. The
      study factors were age, sex, disease duration, and physical function (Health
      Assessment Questionnaire). The sample percentiles were derived empirically, using
      the weighted average method, and their distribution-free confidence limits were
      calculated. Cubic spline interpolation curves were used to smooth the percentile
      lines. RESULTS: We constructed percentile curve reference charts of physical
      function. The best time-dependent variable was increasing disease duration rather
      than increasing age. There was no overlap of the 95% confidence limits for the
      10th, 50th, and 90th percentile curves. CONCLUSION: Percentile curve reference
      charts could be used (1) to describe the distribution of health status in a
      defined population; (2) as an index of change, enabling clinicians to judge the
      success or failure of therapeutic interventions in terms of movement of their
      patients' values across percentiles of function; and (3) to set RA management
      objectives developed from population based norms.

PMID- 7562751
TI  - Comparison of phenytoin with auranofin and chloroquine in rheumatoid arthritis--a
      double blind study.
AB  - OBJECTIVE: To evaluate efficacy of phenytoin in modifying the course of
      rheumatoid arthritis (RA) by comparing it to gold (auranofin) and chloroquine.
      METHODS: A double blind, randomized study of 6 months' duration was conducted at
      the Nizam Institute of Medical Sciences, Hyderabad, India. One hundred and thirty
      two patients with active RA (defined by the 1987 ARA criteria) were entered into
      the study and randomized into 3 groups: phenytoin, chloroquine, or auranofin.
      RESULTS: Full data were evaluable in 100 patients who satisfactorily completed
      the protocol (phenytoin, 35; auranofin, 30; and chloroquine, 35). Twenty-four
      patients were noncompliant and did not take medication or return for evaluation;
      8 patients had the drug withdrawn because of side effects before study
      completion. For each of the 3 drugs all clinical and laboratory variables
      improved when pre and posttreatment values (p < 0.05 to 0.001) were compared.
      There was a greater reduction in posttreatment mean morning stiffness in the
      chloroquine group than in the phenytoin and auranofin groups (p < 0.05).
      Posttreatment grip strength was also greatest in the chloroquine group. On the
      other hand, there were statistically significant decreases in IgM levels in both
      the phenytoin and auranofin groups (p < 0.001), but not with chloroquine. Among
      the 53 patients with a disease history of 3-6 months, global outcome was best
      with phenytoin (16/17), compared to chloroquine (12/18) and auranofin (12/18) (p
      < 0.03). However, there was no such difference in the 47 patients in all 3 groups
      with a disease history longer than 6 months. Eight patients had side effects
      (phenytoin, auranofin, 2; chloroquine, 1) requiring withdrawal of the drug.
      However, the incidence of side effects was not significantly different for the 3
      drugs. CONCLUSION: Our data indicate that phenytoin is comparable to auranofin
      and chloroquine in its efficacy in RA and may be considered an alternative
      disease modifying agent for RA.

PMID- 7562753
TI  - The use of single photon emission computerized tomography in neuropsychiatric
      SLE: a pilot study.
AB  - OBJECTIVE: To test the sensitivity of single photon emission computerized
      tomography (SPECT) in detecting brain abnormalities in cases of definite active
      neuropsychiatric systemic lupus erythematosus (NPSLE) in a blinded, prospective
      pilot study. METHODS: Fourteen patients fulfilling at least 4 of the American
      College of Rheumatology criteria for the classification of SLE plus positive
      serology manifested by either elevated DNA binding or decreased serum complement
      and a recent neuropsychiatric event were evaluated with cerebral SPECT using hexa
      methyl-propylene-amine-oxime labeled 99Tc. Secondary causes such as infection,
      uremia, hypertension, drugs, and metabolic abnormalities were excluded. Patients
      underwent brain scan and electroencephalogram (EEG) for comparison. When
      clinically indicated, CT scan, magnetic resonance imaging, angiography, and
      lumbar puncture were performed. RESULTS: SPECT scan abnormalities were noted in
      12/14 patients and brain scan was abnormal in 12/14 patients. SPECT and brain
      scan were in accordance in 12/14 patients (11 patients both positive and 1 both
      negative) and the combination of SPECT and brain scan yielded 13/14 positive
      results. In the 3 patients with headache, SPECT scan was negative in 2/3, despite
      positive EEG and one with a positive brain scan. The positive SPECT in the
      patient with headache showed an old cerebrovascular accident (CVA), which was
      confirmed by CT scan. The most consistent CT finding was cortical atrophy;
      however, SPECT identified a lesion in the occipital cortex in a patient with
      seizure, and a lesion in the basal ganglia in a patient with ataxia. CONCLUSION:
      In clinically and serologically active NPSLE, SPECT is a sensitive diagnostic
      tool. When further stratifying NPSLE into focal (seizure, ataxia, CVA) and
      diffuse (headache, organic brain syndrome, psychosis), SPECT appeared to be
      sensitive for focal disease and for most diffuse manifestations, with the
      exception of headache. The high sensitivity of SPECT in patients with true,
      positive NPSLE merits further controlled studies in unselected patients with SLE.

PMID- 7562754
TI  - Herpes zoster in systemic lupus erythematosus.
AB  - OBJECTIVE: To define the clinical spectrum and disease sequelae of herpes zoster
      and to determine the risk factors associated with the development of herpes
      zoster in patients with systemic lupus erythematosus (SLE). METHODS:
      Retrospective matched case control study in a consecutive series of patients with
      SLE first evaluated between 1979 and 1989. Patients were classified as cases if
      their first episode of zoster occurred after lupus diagnosis. Lupus patients who
      never had zoster were eligible as controls and were matched 2:1 to cases for age,
      race, sex, and survival status. Clinical features of the cases from the time of
      lupus diagnosis to the time of zoster were compared to their respective controls
      over similar time periods. RESULTS: Forty eight (15%) of 321 patients were
      classified as cases. Cases were more likely to have received cyclophosphamide (p
      = 0.03), and azathioprine (p = 0.006). More cases had lupus nephritis (p = 0.02),
      and a concurrent or previous malignancy (p = 0.01) than their controls. Seven
      cases had cutaneous dissemination. Seven patients had postherpetic neuralgia > 2
      months and in only 2 patients symptoms persisted for > 12 months' duration. Only
      3 of 36 patients had immunosuppressive medication discontinued at the time of
      diagnosis of zoster, and 10 cases received acyclovir for the zoster infection.
      There were no permanent neurologic deficits or death. CONCLUSION:
      Immunosuppressive therapy, specifically cyclophosphamide and azathioprine, lupus
      nephritis, and a concurrent or previous malignancy may be risk factors for the
      development of herpes zoster infections in patients with SLE. Our study suggests
      that although herpes zoster occurs frequently in patients with SLE, it has a
      relatively benign course. Discontinuing needed immunosuppressive therapy in
      patients with SLE may be unnecessary in the setting of a zoster infection. With
      the current emphasis on reduction in medical costs, both by limiting inpatient
      admissions and eliminating unneeded medications, it is necessary to identify
      which patients require more intensive therapy with antiviral medications and/or
      hospitalization and which are likely to have a benign, self-limited course
      without intervention.

PMID- 7562755
TI  - Mortality studies in systemic lupus erythematosus. Results from a single center.
      I. Causes of death.
AB  - OBJECTIVE: To study the causes of death in patients with SLE, followed
      prospectively in a single center. METHODS: The study population comprised 665
      patients with systemic lupus erythematosus (SLE). Causes of death were determined
      by review of hospital files, autopsy reports, and death certificates.
      Nonparametric lifetable models were used to calculate Kaplan-Meier estimates of
      survival probabilities. RESULTS: One hundred and twenty-four patients (18.6%) had
      died. The primary causes of death were active SLE in 20 (16%), infection in 40
      (32%), acute vascular event in 19 (15.4%), sudden death in 10 (8.1%), organ
      failure in 6 (4.8%), malignancy in 8 (6.5%), others in 8 (6.5%), and unknown in
      13 (10.5%). Death as a result of active SLE was more common in patients who died
      within 5 years of diagnosis compared to those dying after 5 years (p = 0.021),
      and deaths due to vascular events and end organ failure not related to active
      lupus were more frequent in the late death group (p = 0.028). The overall 5, 10,
      15, and 20 year survival rates were 93, 85, 79, and 68%, respectively. Patients
      with SLE had a 4.92 fold increased risk for death compared with the general
      population. CONCLUSION: Survival rates continue to improve in SLE but causes of
      mortality vary at different stages.

PMID- 7562756
TI  - Mortality studies in systemic lupus erythematosus. Results from a single center.
      II. Predictor variables for mortality.
AB  - OBJECTIVE: To analyze the factors associated with mortality in patients with
      systemic lupus erythematosus (SLE), followed prospectively in a single center.
      METHODS: The study included 665 patients with SLE followed over a 20-year period
      according to a standard protocol. Clinical laboratory information has been
      entered into a database. Univariate analysis was carried out to identify
      prognostic factors of death. The Cox proportional hazard regression model was
      used to estimate risk ratio of death. RESULTS: Renal damage, thrombocytopenia,
      lung involvement, systemic lupus erythematosus disease activity index (SLEDAI) >
      or = 20 at presentation, and age > or = 50 at diagnosis were predictive factors
      for mortality in the univariate as well as in the multivariate analyses.
      Hypertension and ischemic heart disease were significantly associated with death
      only in the univariate analysis. CONCLUSION: Renal damage, thrombocytopenia,
      SLEDAI > or = 20 at presentation, lung involvement, and age > or = 50 at
      diagnosis are prognostic factors associated with mortality.

PMID- 7562757
TI  - Variability of skin scores and clinical measurements in scleroderma.
AB  - OBJECTIVE: To determine the variability of several clinical outcome measurements
      commonly used in scleroderma clinical trials. METHODS: Ten researchers, members
      of a multicenter placebo controlled trial of methotrexate in early diffuse
      scleroderma, studied the intraobserver and interobserver variability of variables
      used to assess efficacy in scleroderma trials. RESULTS: For most measures, the
      variability within an observer was less than that found between observers, and
      therefore the intraobserver reliability was better than the interobserver
      reliability. The reliability of the modified Rodnan skin score exceeded the
      Rodnan skin score. Measures with inherent interpretation such as global
      assessments and skin scores had more variability than easily performed
      measurements such as grip strength and oral opening. CONCLUSION: Some of our
      variability was higher than variability previously reported; this could be due to
      the large number of examiners and patients in our study.

PMID- 7562758
TI  - Is it possible to reduce observer variability in skin score assessment of
      scleroderma? The ad hoc International Group on the Assessment of Disease Outcome
      in Scleroderma.
AB  - OBJECTIVE: A total skin thickness score based on summating the numerical severity
      grade at a specific number of skin sites is a widely accepted method of disease
      assessment in scleroderma. Our aim was to simplify the modified Rodnan skin
      thickness score (grade 0-3 at 17 sites) by either (1) reducing the number of
      grades or (2) reducing the number of sites, and to increase agreement without
      losing precision. METHODS: Eight patients were examined in random order by 16
      experienced clinicians using the modified Rodnan method. The data were analyzed
      to determine (1) whether there was an improvement in agreement by reducing
      severity grades to a 0-2 scale, (2) whether the precision of the score could be
      maintained by using a reduced number of sites. RESULTS: Collapsing adjacent
      grades from the 0-3 scale to generate 3 new 0-2 scales performed similarly
      (intraclass correlation coefficients 0.66-0.72). A regression analysis showed
      that 95% of the variance in skin score can be predicted by inclusion of scores
      from just 5 sites: forearms, lower legs, anterior chest, upper arms, and fingers.
      CONCLUSION: A simpler skin score may be useful in clinical studies depending on
      the precision required.

PMID- 7562759
TI  - Inter and intraobserver variability of total skin thickness score (modified
      Rodnan TSS) in systemic sclerosis.
AB  - OBJECTIVE: Assessment of the inter and intraobserver variability of the modified
      Rodnan (m-Rodnan) total skin thickness score by clinical palpation [a commonly
      used outcome measure in trials of systemic sclerosis (SSc)]. METHODS: Skin
      thickness was assessed by clinical palpation of 17 body areas on 0 to 3 scale
      (normal, mild, moderate, severe). The m-Rodnan total skin thickness score was
      derived by summation of the scores from all 17 body areas. Using the m-Rodnan, 6
      7 investigators assessed skin thickness in 5-6 patients with SSc (22 patients and
      23 examiners total) at each of 4 sessions for the determination of interobserver
      variability (accuracy). In addition 21 of the investigators then assessed m
      Rodnan in 2-3 patients each (60 patients total) 3 times over a 2-8 week period to
      quantitate intraobserver variability (reliability). RESULTS: Interobserver and
      intraobserver mean +/- within patient standard deviations (SD) for the m-Rodnan
      were found to be 17.7 +/- 4.6 and 20.7 +/- 2.45, respectively. CONCLUSION: The m
      Rodnan total skin thickness score is at least as reliable for measuring skin
      thickness in SSc as are the ARA and Ritchie joint tenderness counts for assessing
      joint disease in rheumatoid arthritis. These data are useful for the
      determination of sample size and for the definitions of clinically meaningful
      response. Assessment of skin score is sufficiently reproducible to include as a
      measure of disease outcome, especially if patients are serially evaluated by the
      same investigator.

PMID- 7562761
TI  - Microscopic polyarteritis has a poor prognosis in Chinese.
AB  - OBJECTIVE: To analyze retrospectively the clinical course and outcome of 10
      consecutive Chinese patients with microscopic polyarteritis (MPA) admitted to our
      hospital over a period of 3 years. METHODS: Ten patients with MPA who presented
      1990-93 were studied. Their serum antineutrophil cytoplasmic autoantibody levels
      were assayed. RESULTS: The male to female ratio was 1:1 and the mean age was 61
      years. Eight patients (80%) had renal impairment on presentation and 5 of them
      (50%) were dialysis dependent. Seven patients (70%), during their clinical
      course, had pulmonary hemorrhage. Six patients (60%) had hypoxic lung disease
      requiring ventilatory support. All 10 patients were pANCA positive; 8 patients
      were tested for antimyeloperoxidase antibody and were all positive. Seven
      patients were treated with immunosuppressants consisting of steroid and
      cyclophosphamide with additional plasma exchange. Nine patients died after a mean
      survival of 9 months (range 1-33); causes of death were respiratory failure (5),
      infection (2), uremia (one), and stroke (one). The ANCA level reflected the
      disease activity of the vasculitis. CONCLUSION: MPA in Chinese patients appeared
      to be a more severe disease with a poor prognosis. This may be related to the
      older age group, and the more frequent and severe pulmonary and renal
      manifestations of MPA in these patients.

PMID- 7562762
TI  - Elevated cancer incidence in patients with dermatomyositis: a population based
      study.
AB  - OBJECTIVE: To study the relationship of polymositis (PM) and dermatomyositis (DM)
      and cancer in Finland. METHODS: The medical records of 175 patients with PM and
      71 with DM diagnosed between 1969 and 1985 were reviewed. The patients were
      followed until death or until December 30, 1990 through the files of Statistics
      Finland and the Finnish Cancer Registry. RESULTS: Thirty-four cases of cancer
      were found [standardized incidence ratio (SIR) 2.1, 95% confidence interval 1.4
      2.9]. In the PM group the SIR was 1.0 (95% CI 0.5-1.8), and in the DM group 6.5
      (95% CI 3.9-10). The relative risk of cancer among DM cases was very high (SIR
      26, 12-48) in the first year after DM diagnosis. CONCLUSION: DM is associated
      with cancer, but not PM. The risk is high among patients with DM older than 49.
      Cytotoxic drugs given to DM patients did not increase the risk of malignancies.
      DM and certain cancers seem to share etiological factors.

PMID- 7562760
TI  - Anti-CENP-B response in sera of uranium miners exposed to quartz dust and
      patients with possible development of systemic sclerosis (scleroderma).
AB  - OBJECTIVE: To look for anti-CENP-B antibodies and their diagnostic relevance in
      patients negative and positive for anticentromere antibodies (ACA) with different
      risk for the development of systemic sclerosis (SSc), including uranium miners
      exposed to quartz dust. METHODS: We studied sera of 107 patients with SSc, 121
      patients with possible SSc, 202 uranium miners heavily exposed to quartz dust, 14
      patients with vibration induced white fingers, and 240 control patients. Subjects
      were screened for ACA by indirect immunofluorescence on HEp-2 cells (IIF-ACA) and
      then for anti-CENP-B autoantibodies by an ELISA using eukaryotically expressed
      human full length recombinant CENP-B protein. RESULTS: All IIF-ACA positive sera
      of "idiopathic" SSc (N = 19), "idiopathic possible" SSc (N = 6) and other
      patients (N = 11), and 17 of 19 IIF-ACA positive sera of miners exposed to silica
      with (N = 13) and without (N = 6) symptoms of SSc reacted with CENP-B in this
      assay. Of the 622 IIF-ACA negative sera, 28 were found positive for anti-CENP-B.
      There was a significant increase of the prevalence of anti-CENP-B antibodies in
      IIF-ACA negative patients with possible SSc (11 of 109) and in miners exposed to
      silica (11 of 196) compared to a group of men older than 60 years with diseases
      or symptoms not related to SSc (1 of 138). CONCLUSION: (1) CENP-B is also the
      major target of the IIF-ACA response in diseases other than scleroderma and in
      the risk group of miners exposed to quartz dust. (2) Anti-CENP-B antibodies can
      be found in IIF-ACA-negative sera, particularly in those at risk for SSc. (3) The
      detection of anti-CENP-B antibodies in miners exposed to quartz dust may indicate
      a high risk group for developing SSc and reveals possibilities for the study of
      early pathogenetic changes as well as exogenic and endogenic factors involved in
      the development of this disease.

PMID- 7562763
TI  - Problem elicitation to assess patient priorities in ankylosing spondylitis and
      fibromyalgia.
AB  - OBJECTIVE: To elicit patient priorities as outcome measures in ankylosing
      spondylitis (AS) and fibromyalgia (FM); to relate these measures to other
      outcomes; to assess construct validity and sensitivity to change of the problem
      elicitation technique (PET) questionnaire. METHODS: One hundred thirty-four
      patients with AS were randomly allocated to weekly sessions of group physical
      therapy or daily exercises at home, whereas 73 patients with FM were randomized
      into one of 3 groups (low impact fitness, biofeedback, controls). The PET
      questionnaire was applied by trained interviewers at baseline and at 6 (FM) and 9
      (AS) month followup. A PET score was calculated at each assessment. Construct
      validity of the PET was assessed by correlation and multiple regression of
      baseline values with other disease outcomes (pain, stiffness, patient's global
      assessment, Sickness Impact Profile (SIP), Health Assessment Questionnaire (HAQ),
      Arthritis Impact Measurement Scale (AIMS), patient utilities). Sensitivity to
      change of PET was assessed against changes in these outcomes and by comparing the
      efficiency of the PET with other outcomes. RESULTS: Patients with FM identified
      more problems (mean 6.8) than patients with AS (mean 4.4). Moreover, more
      patients with AS than with FM were unable to identify any problem at baseline
      (10% compared to 1%). The PET score improved from 14.9 to 11.3 (p = 0.0001) in
      patients with AS but did not change from 21.8 to 21.1 (p = 0.24) in patients with
      FM. Construct validity testing of the PET score showed statistically significant
      (p < 0.05) correlations with AIMS, utilities, SIP, HAQ, pain, stiffness, and
      patient's global health in both groups of patients (r varying from 0.22 to 0.66).
      By multiple regression pain explained 29% of the variance in PET scores among
      patients with AS. In FM patient global assessment accounted for 39% of total
      variance of PET scores, whereas pain explained another 15%. Changes in PET scores
      correlated significantly (p < 0.05) with changes in AIMS, utilities, pain,
      stiffness, and patient global health in both AS and FM (r varying from 0.22 to
      0.51). Some 6% of the variance in changes in PET scores was explained by changes
      in pain in patients with AS and 35% by changes in pain and subjective health in
      patients with FM. Assessment of sensitivity to change revealed that efficiency of
      the PET score was 0.6 in patients with AS and 0.09 in those with FM. Compared to
      other outcomes this was reasonable in patients with AS but low in those with FM.
      CONCLUSION: Obtaining patient priorities was generally feasible. In both groups
      of patients construct validity of the PET questionnaire was satisfactory. The PET
      was much more sensitive to change in patients with AS than in patients with FM.

PMID- 7562764
TI  - Acute local reactions after intraarticular hylan for osteoarthritis of the knee.
AB  - OBJECTIVE: To describe acute local reactions following intraarticular hylan
      injection and determine their frequency. METHODS: Retrospective review of all
      patients with osteoarthritis of the knee treated with hylan by 3 rheumatologists.
      RESULTS: Twenty-two patients had 88 injections to 28 knees. Six patients had
      reactions within 24 h of injection characterized by pain, warmth, and swelling,
      lasting up to 3 weeks. This occurrence was unpredictable. Corticosteroid
      injections were sometimes required. Synovial fluid cell counts were 5.0-75.0 x
      10(9)/l, often with a prominent mononuclear component. Crystal studies and
      cultures were negative. Radiographic chondrocalcinosis was present in only 1
      patient. One patient had serum antibodies to chicken serum proteins. CONCLUSION:
      Intraarticular hylan was associated with significant local inflammatory reactions
      in 27% of patients, or 11% of injections. The mechanism(s) and long term sequelae
      are unclear.

PMID- 7562765
TI  - Effectiveness of spa therapy in chronic low back pain: a randomized clinical
      trial.
AB  - OBJECTIVE: To assess the overall effectiveness of spa therapy compared with usual
      routine drug therapy in chronic low back pain (LBP). METHODS: One hundred and
      twenty-one patients were randomly allocated to treatment (n = 59) and control (n
      = 62) groups. In the treatment group, patients underwent routine drug therapy and
      spa therapy 6 days/week for 3 consecutive weeks in Saint-Nectaire, France. In the
      control group, patients received routine drug therapy. Effectiveness was assessed
      based on clinical measures, duration and intensity of pain, Roland and Morris'
      disability questionnaire, the patient's overall evaluation of back health, and
      drug consumption (analgesic and antiinflammatory). Groups were compared using
      analysis of covariance with repeated measures. RESULTS: At 3 weeks, patients in
      the treatment group had significant improvement in all outcome variables (p <
      0.0001) except for the Schober index and analgesic and antiinflammatory drug
      consumption. At 6 months, improvement was still significant for the same outcome
      variables (p < 0.0001), plus a significant reduction in analgesic consumption.
      CONCLUSION: This study suggests both immediate and 6 month effectiveness of spa
      therapy in chronic LBP. Spa therapy may be beneficial in the management of
      chronic LBP.

PMID- 7562768
TI  - Mononuclear cell (MNC) subtypes in osteoarthritis synovial fluid. Comparison with
      MNC subtypes in rheumatoid arthritis synovial fluid.
AB  - OBJECTIVE: To examine mononuclear cell (MNC) subtypes in osteoarthritis (OA)
      synovial fluid (SF) and compare these results with MNC subtypes in SF from
      patients with rheumatoid arthritis (RA). METHODS: MNC were obtained from SF by
      gradient centrifugation with Ficoll-Hypaque. MNC subtypes were identified using
      color immunofluorescence with monoclonal antibody pairs and flow cytometry.
      RESULTS: Significantly lower percentages of CD3+ (p < 0.01) and CD4+ cells (p <
      0.01) were found in patients with OA. No differences were noted between CD8+
      cells and the CD4/CD8 ratio. Significantly higher percentages of CD14+ (p <
      0.001) and CD16+/CD56+ (p < 0.001) were found in patients with OA. CONCLUSION:
      Significant differences in MNC subtypes in OA and RA were noted that may reflect
      differences in pathophysiologic mechanisms operational in each disease.

PMID- 7562766
TI  - Soft tissue tuberculosis: a series of 11 cases.
AB  - OBJECTIVE: To describe the clinical characteristics of soft tissue tuberculosis
      (TB). METHODS: Retrospective review of all cases of soft tissue TB seen by the
      authors. RESULTS: Eleven cases were seen between 1988 and 1994. All patients but
      one were foreign born. Six patients had collagen vascular disorders and another
      had a kidney transplant. Five were taking immunosuppressive therapy and/or
      prednisone. Three had preceding trauma to the affected area. Five had evidence of
      previous TB by history or chest radiograph. Symptoms (mean duration 4.4 months)
      included swelling and pain and often mimicked the underlying disease. Six
      patients had definite or suspected active TB at other sites. Good initial
      responses were seen with debridement or drainage and multiple drugs for 6 to 12
      months. Two patients have had possible relapses at other sites. Medication
      intolerance was frequent. CONCLUSION: TB should be considered in patients who
      present with unexplained soft tissue swelling and pain, particularly if they are
      immunosuppressed, were foreign born in an endemic area, have an abnormal chest
      radiograph, or have had trauma to the affected area.

PMID- 7562767
TI  - Monocyte-macrophage antigen expression on chondrocytes.
AB  - OBJECTIVE: To characterize chondrocytes in normal and arthritic joints and
      compare their phenotype to that of synovial macrophages present in rheumatoid
      joints. METHODS: Using an immunoperoxidase staining technique, we examined the
      presence and distribution of a number of leukocyte activation and differentiation
      antigens on samples of cartilage obtained from resected joints of normal controls
      and subjects with rheumatoid arthritis or osteoarthritis. RESULTS: Chondrocytes
      in each group were CD14+, CD68+, Thy-1+, CD11a+, CD18+, MAX.3-, and MAX.24-.
      Staining was variable for MAX.1 and CD45. HLA-DR and CD71 were expressed only on
      cells located in the superficial layer of rheumatoid cartilage. We found lower
      levels of expression of CD14 on chondrocytes in arthritic joints, whereas CD58
      was expressed at higher levels. Surface expression of CD14 was confirmed on
      normal chondrocytes using flow cytometry and further supported by the detection
      of CD14 mRNA by polymerase chain reaction. CONCLUSION: Our findings demonstrate
      that chondrocytes express several antigens that are also found on monocytes and
      macrophages.

PMID- 7562769
TI  - Interleukin-1 receptor antagonist inhibits proteoglycan breakdown in antigen
      induced but not polycation induced arthritis in the rabbit.
AB  - OBJECTIVE: To compare the alterations in proteoglycan metabolism in antigen
      induced arthritis and polycation induced arthritis and to determine the
      involvement of interleukin-1 (IL-1) in the cartilage degradation that occurs in
      these models of rheumatoid arthritis (RA). METHODS: The time course for loss of
      proteoglycan into the synovial fluid (SF) and inhibition of proteoglycan
      synthesis, as well as depletion of articular cartilage proteoglycan content, was
      compared in rabbit antigen arthritis and polycation arthritis. The ability of
      recombinant IL-1 receptor antagonist IL-1ra to block the acute cartilage loss at
      24 h in these models was investigated, compared to its ability to block the
      cartilage breakdown induced by direct administration of IL-1 in rabbits. RESULTS:
      Initial loss of cartilage proteoglycan was accompanied by release of high levels
      of glycosaminoglycan (GAG) into the SF and decrease in proteoglycan synthetic
      rates in both antigen and polycation induced arthritis SF GAG rapidly returned to
      control levels, while proteoglycan synthesis and cartilage proteoglycan content
      remained depressed, suggesting that the inhibition in proteoglycan synthesis
      prevented recovery to normal levels. GAG loss from the cartilage into the SF in
      response to IL-1 injection, as well as other effects of IL-1 challenge, was
      blocked in a dose dependent manner by IL-1ra administered either intraarticularly
      (ED50 = 160 ng) or intravenously (iv) (ED50 = 0.09mg/kg). In the antigen induced
      arthritis model, IL-1ra (20 mg/kg, iv -2h) inhibited GAG release by 40%, whereas
      in polycation induced arthritis no inhibition was observed even with repeated
      administration of high doses of inhibitor. CONCLUSION: These studies suggest that
      sustained depression of proteoglycan synthesis may be responsible for the chronic
      depletion of articular cartilage proteoglycan in the antigen and the polycation
      model of RA. However, while IL-1 may play a role in the initial breakdown of
      articular cartilage in antigen induced arthritis, it does not appear to be
      involved in polycation induced arthritis in the rabbit.

PMID- 7562770
TI  - Effects of dietary modification and fish oil supplementation on
      dyslipoproteinemia in pediatric systemic lupus erythematosus.
AB  - OBJECTIVE: To determine if a program of dietary modification and fish oil
      supplementation is effective in treating the dyslipoproteinemia in pediatric
      systemic lupus erythematosus (SLE). METHODS: Prospective clinical trial where
      each patient serves as his/her own control. Twenty-four consecutive adolescents
      fulfilling SLE classification criteria were screened with fasting lipid profiles.
      Patients were identified as having dyslipoproteinemia of active disease or of
      corticosteroid therapy. Patients were treated for 6 weeks with dietary
      modification and if dyslipoproteinemia did not normalize with another 6 weeks of
      dietary modification and fish oil supplementation. RESULTS: Seventeen patients
      (71%) had dyslipoproteinemia; 10 of active disease, 4 of steroid therapy; 3 with
      a combined pattern. Eleven patients underwent dietary modification. There was a
      significant decrease in serum triglyceride concentrations (p < 0.05). Total
      cholesterol, low density lipoprotein cholesterol, and high density lipoprotein
      cholesterol did not change significantly. A further significant decline in serum
      triglycerides was achieved with fish oil supplementation (p < 0.05). Five of the
      11 patients who underwent treatment continued to have dyslipoproteinemia.
      CONCLUSION: Dyslipoproteinemia is common in pediatric SLE. Dietary modification
      and fish oil supplementation appear to be effective in improving serum lipid
      profiles, and blinded studies are warranted. a significant number of patients may
      require pharmacologic therapy for persistent dyslipoproteinemia to prevent
      complications of premature atherosclerosis.

PMID- 7562771
TI  - Clinical and serological identification of 2 forms of complete heart block in
      children.
AB  - OBJECTIVE: To study the association of maternal antibodies to Ro(SSA) and/or
      La(SSB) with isolated complete congenital heart block (CCHB) in children
      according to the child's age at detection. METHODS: Sera from 17 mothers of 18
      children with CCHB of unidentified cause were studied. Autoantibodies were
      measured by double immunodiffusion, enzyme linked immunosorbent assay (ELISA),
      Western blot, and immunoprecipitation from cell extracts. Statistical analysis
      used the chi 2 test with Yates' correction. RESULTS: CCHB was diagnosed in 12
      children of 11 mothers before the age of 3 mo (Group A) and in 6 children of 6
      mothers after the age of 17 mo (Group B). Seven Group A mothers and no Group B
      mother had connective tissue disorders; autoantibodies were found in 9/11 Group A
      and in 1/6 Group B mothers (p < 0.01). Eight Group A children needed a pacemaker
      and one other died of cardiac insufficiency, whereas only one of the 6 Group B
      children needed a pacemaker. Interestingly, this latter child was the only one
      from Group B whose mother's serum contained autoantibodies. Irrespective of their
      age at diagnosis, the children with CCHB who needed a pacemaker and the one who
      died were born to mothers with autoantibodies (p < 0.001). CONCLUSION: CCHB
      detected before the age of 3 mo is highly associated with the presence of anti
      Ro(SSA)/La(SSB) in the mothers, while CCHB diagnosed later is generally not. For
      epidemiological studies, the former type should be considered early onset as
      opposed to late onset CCHB in the latter type. Establishing this
      clinicoserological distinction is also important for the children, since it
      alerts the clinician to a more severe prognosis (necessity of a pacemaker), even
      in the rare occurrence of late diagnosed CCHB.

PMID- 7562772
TI  - Patterns of T lymphocyte clonal expansion in HLA-typed patients with juvenile
      rheumatoid arthritis.
AB  - OBJECTIVE: The presence of clonally expanded T lymphocytes appears to be a
      characteristic feature of autoimmune diseases, including juvenile rheumatoid
      arthritis (JRA), although the relevance of such clones to immunopathogenesis is
      not clear. Identification of clones specific for a disease and/or particular MHC
      haplotypes should help differentiate those of pathogenic importance. METHODS: A
      reverse transcriptase polymerase chain reaction assay for T cell receptor (TCR)
      complementarity determining region 3 (CDR3) length heterogeneity and cDNA
      sequencing were used to identify clonal expansion in synovial fluid (SF) samples
      obtained from 36 patients with JRA. RESULTS: The majority of patients had
      multiple synovial T cell clones using different TCR V beta families. Fifty-eight
      percent of these clonally expanded T cell populations used one of six TCR V beta
      families (V beta 2, V beta 8, V beta 14, V beta 16, V beta 17, and V beta 20).
      Patients with polyarticular, as opposed to pauciarticular, JRA had higher numbers
      of clones in joints. TCR V beta 8, V beta 14, V beta 16, and V beta 17 families
      were most frequently found in these clones. Overall, the most frequently used V
      beta family was V beta 20, which was observed in 18 of 36 SF samples. Of 18
      patients exhibiting TCR V beta 20 clonal expansion, 14 (78%) had pauciarticular
      onset JRA. The V beta 20 association was especially strong in patients who
      possessed HLA-DR8+ haplotypes (p = 0.01, Fisher's exact test). SF from the
      patients who had other types of JRA (and other MHC haplotypes) did not show this
      association. CONCLUSION: The distinct clinical subtypes of JRA are characterized
      by different patterns of synovial T cell clonality. These findings imply that
      different molecular pathways underlie the development of arthritis in each
      subtype of JRA.

PMID- 7562774
TI  - Polyneuropathy in juvenile dermatomyositis.
AB  - We describe 2 patients in whom juvenile dermatomyositis (DM) was associated with
      well defined clinical polyneuropathies, and review the clinical and serological
      data. Light and electron microscopy were used to study muscle and nerve tissues
      from one patient. Neuropathy in our patients was associated with ulcerative skin
      lesions and elevated serum levels of factor VIII related antigen. Light
      microscopic studies of muscle revealed perifascicular atrophy and microinfarcts
      consistent with juvenile DM. Light microscopy of the affected sural nerve showed
      axonal degeneration. Electron microscopy of the same nerve demonstrated capillary
      endothelial inclusions characteristic of those observed as manifestations of
      early endothelial injury in juvenile DM muscle tissue. Polyneuropathy in patients
      with juvenile DM is a rare complication and is likely due to ischemia secondary
      to endothelial damage.

PMID- 7562773
TI  - Elevation of maternal alpha-fetoprotein in systemic lupus erythematosus: a
      controlled study.
AB  - OBJECTIVE: To determine if maternal alpha fetoprotein (AFP) is elevated in lupus
      pregnancy and, if so, whether it is associated with treatment or outcome.
      METHODS: Maternal serum AFP values were obtained once during Weeks 16.3 to 31.7
      in 54 pregnancies followed prospectively. AFP was measured by the Maryland State
      Health Department, who reported the AFP level and a corrected value, multiple of
      the median (AFP MOM), adjusted for weight, gestational age, and insulin dependent
      diabetes. Controls were 1001 consecutive samples measured by the same laboratory.
      RESULTS: AFP MOM was higher in lupus pregnancies (1.425 +/- 0.73 vs 1.169 +/-
      0.50, p = 0.001), as were the unadjusted AFP levels (lupus 68.26 +/- 42.2,
      control 52.49 +/- 27.25, p = 0.001). Of lupus pregnancies 7.4 vs 2.6% of control
      pregnancies had an abnormal AFP MOM (p = 0.06). The 4 patients with abnormal AFP
      MOM, using the 2.3 cutoff, were taking more prednisone (27.25 +/- 18.54 mg vs
      10.85 +/- 12.29 mg, p = 0.02), were more likely to have delivered preterm (31.50
      +/- 36.31 weeks, p = 0.02), and were more likely to have a high anticardiolipin
      (aCL) antibody during the pregnancy (p = 0.03). CONCLUSION: AFP is higher in
      lupus than in control pregnancies, without any increase in neural tube or other
      birth defects. An abnormal maternal serum AFP level is associated with higher
      prednisone dose, preterm delivery and aCL. Patients and obstetricians need to be
      aware that an elevated maternal AFP in lupus pregnancy is not necessarily due to
      a birth defect, and may be predictive of preterm delivery.

PMID- 7562775
TI  - Pancytopenia related eosinophilia in rheumatoid arthritis: a specific
      methotrexate phenomenon?
AB  - Methotrexate (MTX) induced pancytopenia has been reported in about 3% of patients
      with rheumatoid arthritis (RA) receiving low dose MTX. We describe 4 additional
      patients with RA (2M, 2F; mean age 65 yrs; mean duration of RA 9 yrs) who
      developed pancytopenia while receiving low dose MTX. Risk factors identified for
      the development of pancytopenia in our patients included impaired renal function,
      hypoalbuminemia, advanced age, low folate level, concurrent use of multiple
      comedication, nonsteroidal antiinflammatory drugs, and cotrimoxazole).
      Remarkably, pancytopenia related eosinophilia was observed in blood and bone
      marrow after restoring the intracellular folate level by folinic acid. The range
      of eosinophils was 22-56% of the number of peripheral white blood cells (mean
      nadir 33%). The peak level of eosinophilic granulocytes was reached after a mean
      of 6 days in hospital (range 4-8), whereas the peak of neutrophils was reached
      after a mean of 11 days (range 9-13 days). The duration of the eosinophilic
      response was 11 days. As eosinophilia has not been observed in other drug induced
      pancytopenias in patients with RA this could be a specific MTX induced
      phenomenon.

PMID- 7562776
TI  - Anterior dissection of popliteal cyst causing anterior compartment syndrome.
AB  - Dissection and rupture of popliteal cysts occur commonly. We describe a case of a
      13-year-old girl with polyarticular juvenile rheumatoid arthritis who presented
      with anterior tibial swelling and dropped foot. She was found to have dissecting
      popliteal cyst resulting in anterior compartment syndrome.

PMID- 7562778
TI  - Scleroderma, polymyositis, and hairy cell leukemia.
AB  - We report a case of scleroderma myositis overlap, associated with hairy cell
      leukemia. The patient was dramatically improved by treatment with prednisone and
      2'-deoxycoformycin.

PMID- 7562777
TI  - Widespread cutaneous necrosis as the initial manifestation of the
      antiphospholipid antibody syndrome.
AB  - We describe a patient with the acute onset of widespread cutaneous necrosis as
      the initial manifestation of the antiphospholipid antibody syndrome (APS). The
      patient was effectively treated with corticosteroids and anticoagulants, however
      extensive skin grafting was eventually required. We review 6 other reported cases
      and discuss the various underlying etiologies of vascular thrombosis resulting in
      cutaneous necrosis. Early recognition and treatment of the APS may limit the
      extent of thrombotic complications that can result in tissue necrosis.

PMID- 7562779
TI  - Pericardial effusion and vasculitis in a patient with systemic sclerosis.
AB  - We describe a case of diffuse scleroderma with a large pericardial effusion,
      pleural effusions, and subsequent oliguric renal failure. Histology of the
      pericardium and pleura revealed the presence of leukocytoclastic vasculitis.
      Pleuropericarditis in systemic sclerosis may occur on the basis of vasculitis.
      Large pericardial effusions may predispose to subsequent renal failure.

PMID- 7562780
TI  - C5 deficiency in a patient with primary Sjogren's syndrome.
AB  - We report a case of C5 deficiency in combination with Sjogren's syndrome (SS).
      Our patient presented with polyarthritis and complaints of oral and ocular
      dryness. In the serum there was a very low titer of total hemolytic complement
      (CH50) due to a deficiency of the fifth complement component. C5 deficiency is
      often associated with recurrent life threatening infections, membranous
      glomerulonephritis, and discoid lupus erythematosus, but it has not been
      described in association with primary SS.

PMID- 7562781
TI  - Cyclosporin A in the treatment of adult Still's disease.
AB  - Cyclosporin A (CyA) has been used successfully in the treatment of rheumatoid
      arthritis. There is one case report of CyA used successfully in the treatment of
      severe systemic onset Still's disease. To our knowledge, there are no reports of
      CyA used in adult Still's disease. We present the first report of a patient with
      refractory adult Still's disease successfully treated with CyA. We submit that
      cyclosporine treatment may induce remission of symptoms in patients with adult
      Still's disease and reduce the steroid requirements.

PMID- 7562782
TI  - Raynaud's phenomenon as a presenting sign of ovarian adenocarcinoma.
AB  - We describe a 53-year-old white woman whose first manifestation of ovarian
      adenocarcinoma was a sudden onset of severe Raynaud's phenomenon, which rapidly
      progressed to fixed ischemic changes in her thumb. After surgical removal of the
      tumor and chemotherapy, the vasospastic features regressed. To our knowledge this
      is only the 2nd such reported case.

PMID- 7562783
TI  - Ossification of the posterior longitudinal ligament, diffuse, idiopathic skeletal
      hyperostosis, abnormal retinol and retinol binding protein: a familial
      observation.
AB  - We describe a 52-year-old man who presented with diffuse idiopathic skeletal
      hyperostosis, ossification of the posterior longitudinal ligament, and abnormal
      levels of retinol and retinol binding protein (RBP). The molar retinol/retinol
      binding protein ratio was high, suggesting congenital functional RBP deficiency.
      His two sons, aged 23 and 27 years, shared the same biological abnormality
      without clinical symptoms. To our knowledge, this is the first case report of
      such a familial association.

PMID- 7562784
TI  - Principles of economic evaluation for health care programs.
AB  - There is a growing demand for economic evaluation of new therapeutic
      interventions to provide health care decision makers with information on the
      relative value for money offered by alternative treatments. We review the
      rationale for economic evaluation and distinguish between 4 analytic techniques:
      cost minimization analysis, cost effectiveness analysis, cost utility analysis,
      and cost benefit analysis. Each technique is illustrated with an example from the
      literature.

PMID- 7562785
TI  - Economic analysis alongside clinical trials: problems and potential.
AB  - Controlled clinical trials are recognized as the best source of data on the
      efficacy of health care interventions. Because economic evaluation is dependent
      on the quality of the underlying medical evidence, clinical trials have
      increasingly been viewed as the natural vehicle for economic analysis. However,
      the closer integration of economic and clinical research raises many
      methodological issues. This paper discusses these issues in trial design,
      collection of resource use and outcome data, and the interpretation of results.
      Suggestions are made for resolving the major problems.

PMID- 7562786
TI  - Assessing the cost effectiveness of NSAID: an international perspective.
AB  - A number of factors may affect the cost effectiveness of treatments and can cause
      this to vary by location. These factors include the patient population, relative
      price levels, clinical practice patterns and incentives to health professionals
      and institutions such as hospitals. This paper illustrates these issues by
      assessing the relative cost effectiveness of 3 nonsteroidal antiinflammatory
      drugs (NSAID), with different levels of gastrointestinal side effects, in 3
      countries. We conclude that the relative cost effectiveness of drugs is not only
      dependent on drug price but may also vary by country.

PMID- 7562787
TI  - Economic evaluation using mathematical models: the case of misoprostol
      prophylaxis.
AB  - Using misoprostol prophylaxis as an example, many of the methods employed in
      economic analyses that incorporate mathematical models were described. These
      included: decision analysis, cost effectiveness analysis (including incremental
      cost effectiveness analysis), one-way, multi-way, and probabilistic sensitivity
      analysis, and the estimation of quality adjusted life years for use in cost
      utility analysis. In the case of misoprostol prophylaxis, the cost effectiveness
      analysis demonstrated that, compared to the no prophylaxis alternative,
      prophylaxis cost an extra $650, on average, for every additional ulcer prevented,
      and was potentially cost saving for some high risk groups. The cost utility
      analysis demonstrated that prophylaxis resulted (on average) in modest additional
      costs and no additional quality of life benefits. Sensitivity analysis
      demonstrated that, at worst, prophylaxis reduced quality of life; at best, the
      incremental cost effectiveness ratio was $9333 for each quality adjusted life
      year gained by prophylaxis compared to no prophylaxis. The results of the cost
      utility analysis also showed that prophylaxis may be cost saving in high risk
      groups, confirming the results of the cost effectiveness analysis. Finally, and
      perhaps most importantly, this analysis illustrated the importance of
      incorporating measures of health related quality of life into economic
      evaluation.

PMID- 7562788
TI  - OMERACT II: the biologics perspective.
AB  - The development of biologic agents for the treatment of rheumatic diseases will
      necessitate inclusion of pharmacoeconomic analyses in the phase III trials. These
      products are expensive to manufacture, administer, and monitor. Typically, they
      require parenteral administration and regular monitoring. Often the duration of
      benefit is brief; although they may effectively serve as "induction therapy." For
      example, we have a "wonderful new biologic agent," judged effective by the ACR
      preliminary index for improvement, which after 2 treatment courses at +1500 (US)
      each, offers a year of "clinically meaningful" improvement with an acceptable
      safety profile in most patients. How will we convince our regulatory authorities
      and health services agencies that it should be approved and added to our
      formularies? It will be necessary to prospectively collect information about its
      costs (both direct and indirect) and the costs of alternative treatments. In the
      multicenter clinical trials for approval, patients' opinions about their health
      status, quality of life, and the treatment itself must be sought. In addition to
      a disease specific measure of function/disability, a generic measure of health
      status/quality of life should be included. Use of a health utilities instrument
      will allow comparison of different therapeutic interventions. The promise of
      specifically targeting disregulated immune responses without altering underlying
      normal immune function makes biologic agents uniquely attractive for use in an
      early disease population. It will therefore be important to identify those
      indirect costs saved or gained by maintaining function and work capacity, as well
      as the direct (and indirect) costs incurred by treatment associated
      toxicities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562789
TI  - Economic analysis alongside clinical trials: practical considerations. The
      Economics Workgroup.

PMID- 7562790
TI  - Interactive conference voting. The OMERACT II Committee. Outcome Measures in
      Rheumatoid Arthritis Clinical Trial Conference.
AB  - We describe and analyze opinion polling results from interactive voting
      procedures undertaken before and after presentations during the Outcome Measures
      in Rheumatoid Arthritis Clinical Trials Conference (OMERACT II) in Ottawa,
      Canada, June 30-July 2, 1994. The scoring procedure was a matched voting design;
      when a participant used the same keypad at the beginning and end of voting,
      change within a participant could be estimated. Participants, experienced in the
      rheumatic diseases included clinicians, researchers, methodologists, regulators,
      and representatives of the pharmaceutical industry. Patients under consideration
      were those with any rheumatic diseases. Questions were constructed to evaluate
      the change in voting behavior expected from the content of the presentation.
      Statistically significant and substantively important changes were evident in
      most questions.

PMID- 7562791
TI  - How many types of patients meet classification criteria?

PMID- 7562792
TI  - How many types of patients meet classification criteria?

PMID- 7562793
TI  - Cartilage destruction via the synovial fluid in rheumatoid arthritis.

PMID- 7562794
TI  - The role of antiphospholipid antibodies in coronary artery disease in juvenile
      systemic lupus erythematosus.

PMID- 7562796
TI  - Plasma thrombomodulin as a marker of vascular damage in systemic sclerosis.

PMID- 7562795
TI  - Accelerated nodulosis, pleural effusion, and pericardial tamponade during
      methotrexate therapy.

PMID- 7562798
TI  - Guidelines for testing slow acting drugs in arthritis--addendum.

PMID- 7562797
TI  - Purulent abscess after bacillus Calmette-Guerin therapy for bladder cancer.

PMID- 7562799
TI  - Methotrexate benefits in patients with lupus with and without nephritis.

PMID- 7562800
TI  - Pheochromocytoma and pseudovasculitis.

PMID- 7562801
TI  - The meaning of words in the New Health Service.

PMID- 7562802
TI  - The lessons of middle-ear function in non-mammals: improving columellar
      prostheses.
AB  - Due to the simplicity of their manufacture and placement, middle-ear prostheses
      are generally constructed using only a single 'ossicle'. The variety of
      pathologies frequently make it necessary to devise individual solutions and the
      results are often unsatisfactory. Many methods of improving the prostheses have
      been tried, with very mixed results. Even until recently, the fundamental
      assumptions underlying the use of single-ossicle, or columellar, prosthesis have
      been questioned, with suggestions that this type of prosthesis should be
      abandoned in favour of attempts to reconstruct a true three-ossicle middle ear.
      As some of the assumptions in the literature regarding columellar middle ears are
      incorrect and some published information is not easily accessible, a brief review
      of pertinent details of non-mammalian systems is given here.

PMID- 7562804
TI  - Dilemmas of life and death: Part two.

PMID- 7562803
TI  - Sequelae of premature sexual life.

PMID- 7562805
TI  - The oral tumours of two American presidents: what if they were alive today?

PMID- 7562806
TI  - Teenage pregnancy: a comparative study of teenagers choosing termination of
      pregnancy or antenatal care.
AB  - A comparative study of 167 pregnant teenagers in Devon attending either antenatal
      booking clinics or for National Health Service (NHS) termination of pregnancy was
      carried out to determine differences in their characteristics, use and experience
      of local family planning services. Teenagers presenting for termination of
      pregnancy were younger and more likely to say that they had wished to avoid
      getting pregnant. Whether the teenager was in a stable relationship was strongly
      associated with the outcome of the pregnancy, with single girls being more likely
      to choose a termination of pregnancy. The termination of pregnancy group were
      also more likely to be condom users, and to have learned about their method of
      contraception from school rather than from health care professionals. Teenagers'
      frequency of contact with family planning services suggested that teenagers
      choosing a termination were less likely than antenatal attenders to have attended
      regularly. This was mainly due to differences in behaviour among teenagers
      attending their general practitioner (GP) for contraceptive advice: teenagers
      having a termination were more likely to describe their visit to their GP as
      embarrassing. These findings have implications for local family planning services
      attempting to reduce the number of unwanted teenage pregnancies.

PMID- 7562808
TI  - Current practice and future directions in clinical immunology.

PMID- 7562807
TI  - Assessing the effectiveness of a screening campaign: who is missed by 80%
      cervical screening coverage?
AB  - A case-control study was conducted to assess the effectiveness of a regional call
      programme in reaching women at risk of cervical cancer. Home interviews were
      conducted with a random sample of 614 women aged 20-64 who were identified from a
      computerized register as either having had a smear test within the previous 3
      years or not having an up-to-date smear history. Unscreened women fell
      principally into two age cohorts: under 35 years and over 50 years. A small
      social class differential was found to persist following the campaign. Overall,
      unscreened women were not at epidemiologically higher risk than the screened
      population. Thirty-five per cent of unscreened women reported never having had
      sexual intercourse compared to 3% of screened women: 17% of the unscreened and
      38% of screened women reported two or more lifetime sexual partners. No
      difference was observed between screened and unscreened women in the frequency of
      current cigarette smoking (37% unscreened, 38% screened). Cigarette smoking was,
      however, associated with social class (31% classes 1 or 2 compared with 50%
      classes 4 and 5). Level of practical difficulties did not differentiate those who
      attended from those who did not, suggesting that recent changes to delivery or
      screening services have been effective in ensuring equity of access. Non
      attenders and lower class women held more negative attitudes towards the test
      procedure and were less likely to believe that they were at risk of cervical
      cancer. Perceived personal risk was not associated with cigarette smoking,
      suggesting that further attention might be given to this factor in educational
      campaigns.

PMID- 7562809
TI  - Women doctors--a review.
AB  - There have been very marked changes in the number of women doctors who have come
      into the profession in this country in the past 40 years. They have faced
      problems because of society's preconceptions of their role as women. I previously
      reviewed their position in 1975 and 1986, and now take a look at areas where
      progress has been made, and also note whether there is still inequality and where
      women have still not achieved their full potential. I shall make some suggestions
      for improvement.

PMID- 7562810
TI  - Pain and corneal foreign bodies.
AB  - The commonest cause for ocular pain, presenting to an ophthalmic emergency
      centre, is due to corneal foreign bodies. Although the problem is transient, the
      degree of morbidity is often underestimated. The object of this study was to
      assess the degree of pain associated with these lesions.

PMID- 7562812
TI  - Thoracoscopic repair of a transmural rupture of the oesophagus (Boerhaave's
      syndrome).
AB  - Transmural spontaneous oesophageal rupture was first described in 1724 by
      Boerhaave and in 1946 Barrett was the first to describe successful surgical
      treatment for this condition. The advent of minimal access surgery has seen a
      minimally invasive approach to many well recognized surgical conditions and we
      report a thoracoscopic repair of a spontaneously ruptured oesophagus.

PMID- 7562811
TI  - Mozart and medicine in the eighteenth century.
AB  - Over the years the medical history and death of Mozart have been the subject of
      many studies, but in spite of all this attention much remains controversial. In
      an attempt to resolve some of the difficulty it is useful to see his life, and
      that of his family as recorded in their letters, in the context of medicine in
      eighteenth-century Europe.

PMID- 7562813
TI  - Runway malaria in a British serviceman.
AB  - 'Runway malaria' is a clinical entity first described in 1990 and refers to a
      patient who has contracted malaria, in whom the only possible exposure has been
      when the aircraft in which they were travelling has landed transiently in a
      malarious zone. We describe such a case in a British Serviceman travelling from
      the South Atlantic to Germany, who acquired malaria in West Africa.

PMID- 7562814
TI  - Bilateral symmetrical branch retinal artery occlusions.
AB  - We present a report of a 52-year-old hypertensive patient with documented
      bilateral symmetrical branch retinal artery occlusions involving the maculae. The
      patient presented with no visual symptoms and maintained 6/5 unaided visual
      acuity in each eye. Although the incidence of retinal artery occlusion in
      hypertensive patients is well documented, symmetrical bilateral branch retinal
      artery occlusions suggest a possible anatomical vascular predisposition.

PMID- 7562815
TI  - Delayed diagnosis of cystic fibrosis due to normal sweat electrolytes.
AB  - The sweat test, if properly performed, is a reliable tool to assist in the
      diagnosis of cystic fibrosis. In practice, most errors arise from false positive
      results. This case serves as a reminder that false negatives may also occur.

PMID- 7562816
TI  - Reliability of ethics committees.

PMID- 7562817
TI  - Duplex versus angiography.

PMID- 7562818
TI  - A brief journey into medical care and disease in Ancient Egypt.

PMID- 7562819
TI  - Getting the best quality: use the right instrument.

PMID- 7562820
TI  - Primary care at the centre.

PMID- 7562821
TI  - 'Get some research under your belt!'--good advice? A personal view.

PMID- 7562822
TI  - Children coping with the death of a sibling.

PMID- 7562823
TI  - Balancing primary versus specialty care.

PMID- 7562825
TI  - Caffeine dependence: fact or fiction?

PMID- 7562824
TI  - Anticardiolipin antibodies and cardiovascular disease.

PMID- 7562827
TI  - The value of antegrade stenting for lower ureteric obstruction.
AB  - Eleven kidneys in 10 patients (mean age 80 years) presenting over a period of 1
      year with obstruction of the lower ureter secondary to malignant obstruction (8
      patients), stone disease (1 patient), and bladder wall hypertrophy (1 patient)
      underwent nephrostomy with subsequent immediate or delayed antegrade stenting. An
      antegrade placement of the stent was achieved in 10 of the 11 kidneys (90%
      success). In three cases a combined procedure was performed with cystoscopic
      assistance. In most cases there was rapid improvement of renal function following
      stenting. Insertion of ureteric stents in patients admitted to hospital with
      malignant ureteric obstruction allowed treatment of their renal failure and
      subsequent discharge without use of permanent external urinary diversion
      appliances. No significant complications of the procedure were encountered.
      Medium term follow-up of patients stented for malignant ureteric obstruction
      suggests that the stents can be left in place without replacement for up to 20
      months.

PMID- 7562826
TI  - Intracellular (polymorphonuclear) magnesium content in patients with bronchial
      asthma between attacks.
AB  - Previous studies have demonstrated the role of polymorphonuclears in asthma, the
      importance of increases in intracellular concentrations of ionized calcium in the
      release of chemical mediators, the role of magnesium as natural calcium channel
      blocker, and the importance of magnesium deficiency in plasma histamine
      concentration and in tissue prostanoid concentration. The objective of our study
      was to measure the polymorphonuclear magnesium content in patients with asthma in
      the interval between attacks. We measured the polymorphonuclear magnesium
      content, and serum and erythrocyte sodium, calcium, and magnesium concentrations
      in 21 healthy volunteers and 50 patients with different types of asthma. In our
      patients, the polymorphonuclear magnesium content was lower than in the control
      group (P < 0.001), while magnesium levels in erythrocytes and serum and the
      levels of other ions in erythrocytes and serum were normal. This is the first
      report to document low polymorphonuclear magnesium content in patients with
      bronchial asthma. The reduction of polymorphonuclear magnesium content may have
      an important role in the pathogenesis of asthma.

PMID- 7562828
TI  - 'Surgical mules': the smuggling of drugs in the gastrointestinal tract.
AB  - The presentation to surgical units of patients carrying illegal drugs in the
      gastrointestinal tract is a frequent occurrence at hospitals sited close to
      international airports. Drugs, usually heroin or cocaine, are wrapped in
      cellophane packets or condoms. The packages are intracorporeally concealed by
      being swallowed or passed into the rectum. The majority of drug traffickers
      carrying intracorporeal drug packages do not require any medical intervention.
      Recent reports have suggested that these patients are best treated expectantly
      avoiding any operative procedures. However, the quantity of drug in any one of
      the ingested packets is usually above the toxic dose and acute drug toxicity, as
      well as bowel obstruction, can result in fatalities. We report a series of five
      patients who presented over a period of 2 years to a hospital close to Heathrow
      International Airport, London. The presentation and treatment are reviewed and
      the management of such 'surgical mules' discussed. We have shown that
      conservative treatment is appropriate providing bowel obstruction or package
      perforation has not occurred.

PMID- 7562829
TI  - Testosterone deficiency myopathy.
AB  - Testosterone is recognized to have a positive effect on nitrogen balance and
      muscle development in hypogonadal men, but significantly myopathy secondary to
      testosterone deficiency has been reported only rarely. We describe a patient who
      presented with a myopathy associated with testosterone deficiency, and who
      demonstrated a significant functional and myometric response to treatment.

PMID- 7562830
TI  - Before intensive therapy?

PMID- 7562831
TI  - The bloody angle: 100 years of acoustic neuroma surgery.

PMID- 7562832
TI  - Pet-FDG imaging in the clinical evaluation of head and neck cancer.

PMID- 7562833
TI  - The hazards of using a child as an interpreter.
AB  - When a language barrier prevents communication with immigrant parents, there may
      be a temptation to use a bilingual child as an interpreter. We report a possible
      hazard.

PMID- 7562834
TI  - Endophthalmitis after routine intra-ocular surgery in an asplenic patient.
AB  - A 72-year-old asplenic man developed an acute early pneumococcal endophthalmitis
      after a routine endocapsular cataract extraction with poor final visual outcome.
      It is recognized that splenectomy increases the risk and severity of pneumococcal
      infections. Our patient had not received pneumococcal vaccination or been
      prescribed prophylactic antibiotics since his splenectomy or at the time of
      surgery. Failure of these measures to occur may have affected visual outcome.

PMID- 7562835
TI  - Erythropoietic protoporphyria presenting in an adult.
AB  - Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism,
      in which reduced activity of the enzyme ferrochelatase leads to accumulation of
      protoporphyrins in erythrocytes. Protoporphyrins are photoactivated by ultra
      violet light causing tissue damage by release of free oxygen radicals, which
      manifests as photosensitivity. The majority of cases of erythropoietic
      protoporphyria present in childhood although sometimes symptoms are delayed until
      the second decade. We report here a case presenting in adulthood and discuss the
      risk of liver disease in the condition.

PMID- 7562836
TI  - Percutaneous endovascular covered stenting of a distal superficial femoral artery
      occlusion.
AB  - Peripheral vascular disease is a common problem in the elderly population. This
      is commonly treated nowadays by percutaneous transluminal angioplasty (PTA). When
      PTA is used in the treatment of superficial femoral artery (SFA) occlusions 35%
      reocclude within 1 year. Endovascular stents (uncovered) have been used to try to
      overcome this problem; however, results have been disappointing with reocclusion
      rates similar to PTA. In order to try to reduce this problem covered endovascular
      stents have been developed. We report the first known case in the UK of one of
      these stents being used in the treatment of SFA disease.

PMID- 7562837
TI  - Restorative proctocolectomy for Chagasic megacolon.
AB  - Chagas' disease is endemic in South America, affecting several million people.
      Megacolon, the commonest intestinal manifestation, causes severe constipation and
      usually requires surgery. We report a case which was treated by restorative
      proctocolectomy. We believe this to be a useful new technique in the treatment of
      this condition.

PMID- 7562838
TI  - Improving the documentation and appropriateness of cardiopulmonary resuscitation
      decisions.

PMID- 7562839
TI  - The genetic background of anticipation.

PMID- 7562841
TI  - Traditional Chinese medicine and public health: the Yin and the Yang.

PMID- 7562840
TI  - Chopin's illnesses.

PMID- 7562842
TI  - Malnutrition and mortality.

PMID- 7562843
TI  - Anatomy of a physiological discovery: William Harvey and the circulation of the
      blood.

PMID- 7562844
TI  - Post-prandial hypotension in the elderly.

PMID- 7562845
TI  - Modern opioids: uses defined by chrono-pharmacology, not receptor selectivity.

PMID- 7562846
TI  - The role of fluoride toothpastes in the prevention of dental caries.

PMID- 7562847
TI  - Parental presence during procedures: a survey of attitudes amongst
      paediatricians.
AB  - As a child's primary caretaker, the parent plays a significant role in the
      management of paediatric pain. Is this what physicians want and allow? This paper
      analyses the results of a survey conducted among paediatricians. Three hundred
      and fourteen consultant paediatricians were sent questionnaires about their
      attitudes towards parental presence during medical procedures performed on
      children under local anaesthesia. Paediatricians were asked under what
      circumstances they allowed parents to remain, and what factors led to their
      exclusion. The response rate was high--60.8%. Though 98.5% of paediatricians were
      willing to let parents remain, 57.5% excluded some parents from certain
      procedures, particularly if parents were anxious and the procedure difficult or
      painful. Ninety-one per cent relied on verbal explanations alone to prepare
      parents prior to procedures.

PMID- 7562849
TI  - Psychiatric consequences of radical curative surgery for gastric cancer.
AB  - Radical resection of gastric cancer offers the best hope of cure, but carries the
      risk of significant psychological morbidity in addition to the well-documented
      physical complications. In the case presented, recognition of clinical depression
      after thoracoabdominal gastrectomy enabled successful psychological intervention.

PMID- 7562848
TI  - NATALI--a model for National Computer Databases in the investigation of new
      therapeutic techniques.
AB  - New medical treatments are often introduced without the benefit of randomized
      trials. We describe how a national computerized database was produced, by the
      Thrombolysis Study Group, for monitoring one such new treatment: peripheral
      arterial thrombolysis. A novel method for transferring angiograms to computer
      generated arterial maps that can help in the classification and analysis of the
      outcome of thrombolysis is also described. Data provided by prospective
      collection from 14 hospitals within the UK was entered onto the database
      (Auditbase for Windows), to give contributing members a continual audit of their
      own results and complications that can be compared with that of the group as a
      whole. This system may be an appropriate model for other forms of multi-centre
      audit and the monitoring of new treatments.

PMID- 7562851
TI  - Audit of post-operative auto-transfusion of shed blood in hip arthroplasty.
AB  - Auto-transfusion of shed blood for joint arthroplasty has several theoretical
      advantages: availability, compatibility, avoidance of transmission of infection
      and cost. The clinical records of 92 primary hip arthroplasties were reviewed to
      investigate the effect of auto-transfusion on the use of the National Blood
      Transfusion Service both in terms of blood ordered and subsequently used.
      Overall, post-operative auto-transfusion had no significant effect on blood
      ordering or usage and was very expensive. The majority of patients were over
      transfused.

PMID- 7562850
TI  - A celebration of women in anaesthesia 1894-1994.

PMID- 7562852
TI  - Pitfalls in accident and emergency chest pain evaluation.

PMID- 7562853
TI  - O'Brien's actinic granuloma: response to isotretinoin.
AB  - We describe a 75-year-old man demonstrating the florid clinical features of
      actinic granuloma of O'Brien. This rare disfiguring condition is believed to
      result from a granulomatous reaction of the dermis to solar-induced elastosis and
      is poorly responsive to topical steroids. Twelve weeks' treatment with
      isotretinoin prevented the development of new granulomata and produced almost
      complete resolution of established lesions.

PMID- 7562855
TI  - Renal autotransplantation for aortic dissection in Marfan's syndrome.
AB  - Marfan's syndrome is an autosomal dominant condition with a prevalence of 4 to
      6:100,000, and classically comprises skeletal changes, ectopia lentis and cystic
      medial necrosis of the largest arteries. The latter leads to aneurysm formation,
      most often commencing at the aortic root, and is responsible for an average age
      at death of 32 years. We describe successful preservation of threatened renal
      function by renal autotransplantation, without concurrent aortic replacement,
      following dissection of the descending aorta in a patient with Marfan's syndrome.

PMID- 7562854
TI  - Urticaria pigmentosa and acute lymphoblastic leukaemia.
AB  - Childhood urticaria pigmentosa is generally considered to have a good prognosis
      with the majority of cases undergoing spontaneous resolution. However, there have
      been a number of reports of haematological malignancies occurring in association
      with urticaria pigmentosa. We describe a child with extensive urticaria
      pigmentosa and a congenital cardiac anomaly who developed acute lymphoblastic
      leukaemia and suggest a possible common aetiology.

PMID- 7562857
TI  - The 'Pinocchio' nasal deformity due to cavernous lymphangioma.
AB  - The 'Pinocchio' or 'Cyrano' nose is a rare condition in which deformity of the
      nasal tip is produced by an underlying soft tissue tumour. Previously reported
      cases have been due to either capillary or cavernous haemangiomas (angiolipomas).
      The deformity is the cause of much teasing in children. There has been debate as
      to whether surgical intervention is indicated, as a proportion of cases will
      regress spontaneously. We report a case of 'Pinocchio' nose with a lymphangioma
      of the nasal tip which is previously undescribed and review the options for
      management.

PMID- 7562856
TI  - Remission of recurrent mature teratoma with interferon therapy.
AB  - Although alpha-interferons have anti-tumour activity in a variety of solid and
      haematological malignancies, they are not generally considered to be effective
      therapy for mature testicular teratomas. We report a case of complete remission
      in a patient with recurrent mature teratoma following treatment with alpha
      interferon.

PMID- 7562858
TI  - Breastfeeding.

PMID- 7562859
TI  - Osteoarthritis in old age.

PMID- 7562860
TI  - Clinical case reports.

PMID- 7562862
TI  - Fungal feeding-line infection.

PMID- 7562861
TI  - Expert witness.

PMID- 7562863
TI  - John Knight and The King's Healing.

PMID- 7562864
TI  - Rebound exacerbation of anxiety during prolonged tranquilizer ingestion.

PMID- 7562866
TI  - Explaining the French paradox.
AB  - The 'French paradox' refers to the very low incidence of and mortality rates from
      ischaemic heart disease in France despite the fact that saturated fat intakes,
      serum cholesterol, blood pressure and prevalence of smoking are no lower there
      than elsewhere. To some extent it is due to under-reporting, but this is not the
      whole explanation. The relative immunity of the French to ischaemic heart disease
      has been attributed to their high alcohol consumption and to their intake of
      antioxidant vitamins, both being supplied by wine. The custom of drinking wine
      with the meal may confer protection against some of the adverse effects of the
      food.

PMID- 7562865
TI  - Vegetable and fruit consumption: some past, present and future practices.
AB  - In Western populations, historically, from early times until the 19th century,
      diets were composed largely of plant foods-cereals, beans, vegetables and fruit.
      The huge majority of populations were very poor with restricted food choices. The
      same situation prevails with most present-day Third World populations, although
      principally with rural dwellers. In Western populations, in recent times,
      stemming largely from urbanization and rise in prosperity, and accompanying
      increased partiality to animal foods, there have been falls in the intake of some
      plant foods yet rises in others. Potato intake has halved, whereas vegetable
      consumption has increased only slightly, although that of fruit more so. National
      consumptions of these foodstuffs vary widely, those in the United Kingdom and
      United States of American being only about half of those in Mediterranean
      countries, Spain, Portugal and Greece. In the former countries, present dietary
      guidelines urge that vegetable consumption be doubled, with fruit up by a half.
      In southern Africa, consumption of vegetables and fruit by the white population
      appears similar to those in The USA and UK. Yet in African cities, intake is low
      due to their cost. In view of the protective role of high vegetable and fruit
      intake in the combating of coronary heart disease and many forms of cancer, the
      relatively low consumption of these foodstuffs, especially in the poorer
      populations, is disappointing, and alas, appears unlikely to rise in the near
      future.

PMID- 7562867
TI  - Psychosocial context of stress in health and illness.

PMID- 7562868
TI  - The role of nicotine in tobacco smoking: implications for tobacco control policy.
AB  - This paper outlines some of the evidence that tobacco smoking is maintained by
      addiction to nicotine. Smokers often perceive that tobacco helps them cope with
      stress and aids their mental alertness. Nicotine withdrawal symptoms are one
      important factor preventing many smoker from quitting (only about 3% succeed with
      each unaided quit attempt). A number of policies are suggested to reduce the
      health consequences of smoking more quickly than at present. These include (a)
      banning all tobacco advertising and prosecuting retailers who sell illegally to
      children, in order to reduce the number of young people becoming addicted, (b)
      increasing the real price of tobacco in order to encourage more people to try to
      stop smoking, (c) providing specialist smokers' clinics in every large general
      hospital in order to assist highly motivated but addicted smokers to quit and (d)
      increasing the rate at which tobacco manufacturers must reduce permissible tar
      and carbon monoxide yields, such that in 20 years time only nicotine delivery
      products which are free of tar and carbon monoxide will be allowed.

PMID- 7562869
TI  - Compliance with short-term antibiotic therapy among patients attending primary
      health centres in Riyadh, Saudi Arabia.
AB  - Non-compliance results in several undesired consequences. Admissions due to non
      compliance have been estimated to account for up to 10.5% of all admissions to
      hospital. There seems to be very little data about compliance in Saudi Arabia.
      The present study addressed the problem of non-compliance with short-term
      antibiotic therapy in patients attending Primary Health Centres (PHC). The data
      were collected from five different centres selected randomly from the 53 centres
      in the Riyadh area, Saudi Arabia. A five-part questionnaire was designed and used
      to collect data. Different parts were required to be completed by patient,
      doctor, pharmacist and social worker. At the end of the study period 414
      questionnaires were suitable for evaluation. Paediatric patients (< 15 years old)
      constituted 65.9% of the sample. Compliance was noted in 67.8%. Those who missed
      three doses or less and more than three doses were 22.7% and 9.4% respectively.
      Factors which appeared to enhance patient compliance were: parental involvement
      (p < 0.001), unemployment (p < 0.01), absence of psychiatric illness (p < 0.02)
      and early improvement of symptoms (p < 0.05). Reasons most frequently mentioned
      by patients for non-compliance were: rapid improvement of symptoms, bitter taste
      of drug(s), forgetfulness and frequent dosing. These reasons accounted for 73.7%
      of reasons for non-compliance. Our findings suggest that approximately two thirds
      of patients were compliant with their medications. It is also worth noting that
      approximately three quarters of patients were not compliant for reasons which
      could be minimised or removed by good patient counselling and effective
      communication with patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562870
TI  - Self-reported incidence of accidental exposures to patients' blood and body
      fluids by resident doctors in Nigeria.
AB  - An anonymous survey of 149 resident doctors was conducted to estimate the extent
      of accidental exposures to blood and body fluids of patients over a one-year
      period. There was a total of 1142 exposures. Ninety-three percent of respondents
      reported one or more exposure incident(s). Analysis of events and procedures
      leading to accidental exposures revealed that recapping needles was involved in
      17%, suturing accounted for 14%, setting up intravenous lines 11%, cuts with
      scalpel 9% and phlebotomy 9%. Surgical residents had a threefold greater risk of
      exposure compared with medicine residents. No trend was found for accidental
      exposures by level of residency training. Seventy-four percent of the residents
      used universal precautions 50% or less of the time. Only half of the doctors
      could recall formal instruction on correct course of action after exposure and 5%
      of them had as undergraduates hepatitis B vaccine prior to the commencement of
      venepuncture duties. All but one of the residents' exposures were not reported to
      the Staff Medical Services Department. The doctor who reported was neither tested
      for hepatitis B virus or human immunodeficiency virus nor was he properly
      treated. Only 5 (4.6%) of the contaminating patients were evaluated serologically
      for their status of these viruses. These data emphasize the need for increased
      efforts toward improved early and continuing education, prevention and correct
      management of accidental exposures to blood or body fluids of patients by
      resident doctors in Nigeria. No recent study exists that exclusively addresses
      this problem in doctors in tropical Africa.

PMID- 7562871
TI  - A study of nosocomial infection in relation to different host factors in an
      Indian teaching hospital.
AB  - Out of a total of 422 patients studied, 164 (38.8%) developed nosocomial
      infection. The rate was higher (41.6%) in males than in females (34.7%). A rising
      trend of infection was observed with age, maximum (69.6%) being in the above 60
      age group. Nosocomial infection rate was inversely proportional to the socio
      economic status of the patient. At the same time some underlying diseases in the
      patients influenced the rate of infection to a great extent, eg infection rates
      in patients with anaemia (53.7%), diabetes mellitus (85.2%), hypertension (82.0%)
      and obesity (51.5%) were much more than in patients with no such underlying
      disease (17.5%).

PMID- 7562872
TI  - Hazard analysis and the caterer.

PMID- 7562873
TI  - HACCP implementation in food businesses: the need for a flexible approach.
AB  - There is a considerable literature on microbiological hazards which cause food
      borne diseases and illnesses, and factors which influence their occurrence and
      growth in foods. Similarly, stages in the food chain where foods may be
      mishandled, and practices which often lead to outbreaks of food-borne diseases
      are well documented. Although these hazards and practices can be controlled in
      order to prevent or minimise risks to health, food-borne diseases have continued
      to present a serious challenge to public health. Because the traditional
      approaches of inspection and end-product testing have proved inadequate in
      tackling the problem of food-borne diseases, there is an urgent need to apply
      more rational and effective strategies. One such strategy is the Hazard Analysis,
      Critical Control Points (HACCP) system which is currently in international
      discussion. This paper examines the epidemiological basis for the application of
      HACCP to food safety control and describes its advantages. It is concluded that
      to realise the objectives of HACCP, a flexible and simple approach is needed in
      its practical application across food businesses. Any argument that the system
      cannot be applied without fully developed and well structured food systems will
      ultimately reduce its potential usefulness in food safety control.

PMID- 7562874
TI  - An introduction to health and safety in the laboratory.

PMID- 7562876
TI  - Assessment: the view from the private sector.

PMID- 7562875
TI  - Users, carers and care agencies--conflict or co-operation?

PMID- 7562877
TI  - Public health in the United States.

PMID- 7562878
TI  - Managed health care.

PMID- 7562879
TI  - Poisoning with anti-hypertensive drugs: alpha-adrenoceptor antagonists.
AB  - Experience with overdosage and toxicity with the alpha (alpha)-adrenoceptor
      antagonists remains very limited, and all the cases in the literature relate to
      prazosin overdosage. The selective alpha-blocker appears, however, to have a low
      acute toxicity. Supportive therapy by the reduction of gastrointestinal
      absorption, monitoring of vital signs and the correction of hypotension (with
      intravenous fluids) is indicated.

PMID- 7562880
TI  - Relation between family history of hypertension, overweight and ambulatory blood
      pressure: the HARVEST study.
AB  - The aim of the present paper was to evaluate the influence of a family history of
      hypertension and the degree of obesity as indicated by tertiles of body mass
      index on ambulatory blood pressure (BP) values in large number (n = 406) of young
      mild essential hypertensives. Positive family history of hypertension was
      associated with a significant increase in 24h ambulatory systolic blood pressure
      (SBP). The difference was most pronounced in the upper tertile of body mass index
      with almost 6 mm Hg difference between patients with and without a family history
      of hypertension. Both the degree of obesity and family history of hypertension
      had significant effects on 24h diastolic blood pressure (DBP). Twenty four hour
      DBP was highest in the upper tertile of body mass index in the hypertensives with
      a positive family history, representing an increase of 5 mm Hg compared with
      patients with a negative family history in the lower tertile. We conclude that
      mild hypertensives with a positive family history of hypertension are
      characterised by higher ambulatory BP than patients without parental hypertension
      and similar supine BP. Furthermore, our results indicate that in mild
      hypertensives the increase in DBP with body mass index is underestimated by
      conventional sphygmomanometry.

PMID- 7562881
TI  - Determination of systemic haemodynamic alterations induced by slow-release
      nifedipine in elderly hypertensive patients using a non-invasive method: double
      blind cross-sectional random study.
AB  - We evaluated the systemic haemodynamic alterations induced by slow-release
      nifedipine administered to elderly hypertensive patients, 20 mg twice daily by
      the oral route for 4 weeks. A non-invasive chest electrical bio-impedance method
      was used to detect changes in stroke volume and cardiac output. The random,
      double-blind, crossover study showed variations in measurements made in the
      supine and in the standing position: delta -18.0% (P < 0.001) and delta -14.9% (P
      < 0.001) for mean arterial pressure; delta -16.5% (P < 0.01) and delta -34.9% (P
      < 0.01) for total peripheral resistance; and delta +8.1% (P < 0.05) and delta
      +12.6% (P < 0.01) for heart rate, respectively. In contrast, cardiac output and
      stroke volume were the same when measured in the supine and standing positions
      both when compared with the placebo period and when compared with each other. We
      conclude that slow-release nifedipine is effective in reducing systemic blood
      pressure levels of elderly subjects and that this phenomenon occurs without
      reductions in cardiac output.

PMID- 7562882
TI  - Lisinopril administration improves insulin action in aged patients with
      hypertension.
AB  - Thirty elderly, mildly hypertensive patients were enrolled for a single-blind,
      randomised cross-over placebo controlled trial in which placebo and lisinopril
      (20 mg/day before breakfast) were given for 4 and 8 weeks, respectively. A wash
      out period of 3 weeks between placebo and lisinopril was observed. In each
      patient a euglycaemic glucose clamp with simultaneous indirect calorimetry
      allowed us to determine whole body glucose disposal and substrate oxidation.
      Changes in morning SBP and DBP were also determined. Lisinopril vs. placebo
      significantly improved whole body glucose disposal (40.4 +/- 0.4 vs. 30.3 +/- 0.4
      mumol/kg LBM x min; P < 0.01), non-oxidative glucose metabolism (18.1 +/- 0.7 vs.
      10.9 +/- 0.6 mumol/kg LBM x min; P < 0.01) and fasting plasma potassium levels
      (4.8 +/- 3 vs. 4.4 +/- 0.4 mmol/l; P < 0.05). SBP (175 +/- 3.3 vs. 160 +/- 3.0 mm
      Hg; P < 0.001) and DBP (106 +/- 2.3 vs. 95 +/- 2.0 mm Hg; P < 0.001) were
      significantly reduced by lisinopril administration. After ACE inhibition, fasting
      plasma potassium levels correlated with the decline in mean arterial BP (r = 
      0.71; P < 0.006). In conclusion, lisinopril administration reduces arterial BP
      and improves insulin sensitivity in elderly hypertensive patients.

PMID- 7562883
TI  - Study of the usefulness of optic fundi examination of patients with hypertension
      in a clinical setting.
AB  - The purpose of this study was to evaluate the usefulness of direct opthalmoscopy
      by non-opthalmologists in patients with hypertension. In a cross-sectional
      survey, we analysed the association between optic fundi abnormalities,
      individually and according to the criteria of Keith and Wagener (KW), with blood
      pressure and duration of known hypertension in 400 non-diabetic hypertensive
      patients. The optic fundi abnormalities were more frequent in patients with
      diastolic blood pressure (DBP) > 105 mm Hg (P = 0.002), SBP > 180 mm Hg (P <
      0.0001) and with a duration of known hypertension > 3 years (P = 0.002). The
      severity of hypertension did not vary in parallel with the KW classes I and II:
      34.5% of patients classified as KW I had a diastolic pressure of > 105 mm Hg
      compared with only 25.3% of those classified as KW II. Class III abnormalities
      were infrequent (2.5% of the whole cohort). In a logistic regression model,
      diffuse arteriolar narrowing was associated with DBP (P = 0.002) and age (P <
      0.001). Abnormalities of the arteriovenous crossings were associated with SBP (P
      = 0.001) and duration of disease (P = 0.008). The positive predictive value of
      any fundoscopic abnormality to estimate the severity of hypertension was 59% and
      the negative value was 60%. The results of this study demonstrate that optic
      fundi examination by internists and cardiologists does not give an accurate
      assessment of the severity of hypertension in most patients, and that the Keith
      Wagener classification of retinopathy has a limited applicability.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7562884
TI  - Lack of association between HLA class II polymorphisms and essential hypertension
      in a Belgian population.
AB  - The aim of the present study was to investigate whether the HLA class II
      polymorphisms contributes to the susceptibility to essential hypertension in the
      Belgian population. For this purpose we studied 120 hypertensive patients and 168
      normotensive controls by means of a PCR-SSO assay. No significant difference in
      allele and genotype frequencies of the DRB and DPB1 loci could be found between
      the two groups. We concluded that essential hypertension as a multifactorial and
      heterogeneous disease cannot be associated with one of the HLA class II DRB and
      DPB1 alleles in Belgian patients.

PMID- 7562886
TI  - Characteristics of a reversed circadian blood pressure rhythm in pregnant women
      with hypertension.
AB  - The objective of the study was to describe the 24h blood pressure (BP) pattern in
      pregnant women with a reversed circadian BP rhythm. The 24h BP monitorings
      (24BPM) were performed in 73 pregnant women hospitalised for hypertension.
      Daytime (6.00 am to 10.00 pm) and night-time (10.00 pm to 6.00 am) BP variables
      were calculated. A reversed circadian BP rhythm was defined as a day/night mean
      BP ratio < 1.0. Fourteen women had a reversed circadian BP rhythm. Their diurnal
      mean BP was equal to women with a normal rhythm, but their nocturnal mean BP was
      significantly higher and their BP oscillation amplitudes tended to be lower. The
      day/night mean SBP and DBP ratios correlated significantly, with the DBP ratios
      slightly higher than corresponding SBP ratios. At repeated 24BPM (n = 14), the
      day/night ratio did not change but a reversed rhythm occurred during anti
      hypertensive medication in one case, and a reversed rhythm switched spontaneously
      to normal in one case. The diurnal BP pattern did not differ between women with a
      reversed and a normal circadian BP rhythm. Women with a reversed rhythm had a
      higher nocturnal BP, but this was part of the definition. The BP variations were
      generally smaller in the group with a reversed rhythm, although the variations
      were still large. The definition with a day/night ratio cut-off at 1.0 was rather
      a convenient mathematical choice than a biologically-determined limit. The
      day/night BP ratio remained unchanged at repeated measurements, but a reversed
      rhythm was not a constant phenomenon in occasional cases. Women with a reversed
      circadian BP rhythm were therefore not a well-defined group and, with exception
      for a tendency to smaller BP fluctuations, no specific behavioural BP pattern
      could be described. Until the normal circadian BP rhythm in normal pregnancy has
      been described, there is no possibility to identify women with an abnormal
      circadian BP rhythm. Ideally, any definition of an abnormal rhythm should be
      related to the clinical relevance.

PMID- 7562885
TI  - Changes in plasma lipids, lipoproteins and apolipoproteins in
      hypercholesterolaemic patients treated with pravastatin.
AB  - Plasma lipids, lipoproteins and apolipoproteins were studied before and during 6
      months of pravastatin administration in patients with hypecholesterolaemia. After
      a 1 month placebo run-in period, the patients were treated double-blind either
      with placebo (n = 25) or with pravastatin (n = 25) for 6 months. Placebo or
      pravastatin 10 mg during the first month, 20 mg during the second month and 40 mg
      during the additional 4 months was administered once daily in the evening.
      Compared with the placebo group the plasma concentration of total cholesterol and
      phospholipids, free cholesterol and cholesterol esters as well as the plasma LDL
      cholesterol and LDL-phospholipids were decreased during 6 months of pravastation
      therapy. No changes in plasma VLDL-, HDL-, HDL2-, or HDL3-cholesterol, 
      phospholipids or -triglycerides were observed in the pravastatin-treated
      patients. A decrease in the plasma level of apolipoprotein B and of LDL-apo B,
      but not of VLDL-apo B, was observed during pravastatin therapy; the plasma
      apolipoprotein AI and AII levels as well as HDL2- and HDL3-apo AI and apo AII
      levels remained, however, unchanged. Plasma lipoprotein Lp(a) did not change
      during pravastatin therapy whereas the plasma lecithin cholesterol
      acyltransferase activity (LCAT) increased. In conclusion, treatment of
      hypercholesterolaemic patients with pravastatin results in a decrease in the
      plasma concentration of total and free cholesterol, LDL-cholesterol,
      apolipoprotein B, LDL-apo B, phospholipids and cholesterol esters and in an
      increase in plasma LCAT activity. Plasma Lp(a), HDL-cholesterol and triglyceride
      levels remained, however, unchanged.

PMID- 7562887
TI  - Hawksley random zero sphygmomanometer versus the standard sphygmomanometer: an
      investigation of mechanisms.
AB  - There has been recent controversy over the accuracy of the Hawksley random zero
      sphygmomanometer (RZS). In most instances, there has been a bias towards lower
      recordings with the RZS. In an attempt to identify the mechanism, we designed a
      study to test the hypothesis that biased error is due to: (1) the magnitude of
      the random zero; and (2) the magnitude of the pressure being recorded. A RZS (60
      mm Hg zero UK version) was connected via a Y-tube to a standard mercury
      sphygmomanometer (SMS). The circumference of the cam responsible for the variable
      reservoir size in the RZS was marked into quarters. Within each 10 mm Hg band
      from 300 to 60 mm Hg, 12 paired readings were taken randomly: three within each
      of the four quarters of the cam circumference. The mean SMS value was 148.8 vs.
      148.2 mm Hg for the RZS. Although of minimal biological significance this
      difference was highly significant (t = 6.2; p < 0.0001). Our findings fail to
      confirm the difference between RZS and SMS previously reported and we did not
      find any evidence of a relation in the difference between SMS and RZS and either
      the random zero value or the height of the blood pressure. Our findings suggest
      that if the RZS does under record BP versus the SMS it may relate to a patient
      machine interaction not detectable in our system.

PMID- 7562888
TI  - Measurement of trough-to-peak ratios of four anti-hypertensive drugs on the basis
      of 24 h ambulatory blood pressure monitoring: different methods may give
      different results.
AB  - With 24 h ambulatory blood pressure monitoring (ABPM), the trough-to-peak (T/P)
      ratios (corrected for placebo) of atenolol 100 mg, cilazapril 2.5 mg, enalapril
      20 mg and nifedipine-GITS 30 mg administered once daily for 4 weeks were
      determined in four groups of hypertensive patients. T/P ratios were calculated by
      three different methods: directly from the curves that averaged all individual 24
      h profiles (A); averaging all individual T/P ratios after ABPM data were averaged
      for each patient over either 1 h intervals (B) or 3 h intervals (C). Methods B
      and C produced different values of T/P which, for each drug, were significantly
      higher with method C. With method A, nifedipine appeared to have the higher T/P.
      With methods B and C (which in contrast to method A, permitted statistical
      comparisons), differences between nifedipine and the other drugs were not
      significant. Meanwhile, method B appears to adhere most closely to FDA guidelines
      by taking more into account the interindividual variability of BP profile. Thus,
      we suggest that precise guidelines for measuring T/P on the basis of ABPM are
      needed, whereas for the comparison between drugs, both the mean value of the T/P
      and its variance must be determined.

PMID- 7562889
TI  - Relation between age, left ventricular mass and ventricular arrhythmias in
      patients with hypertension.
AB  - To evaluate the effect of age on left ventricular hypertrophy-related arrhythmias
      in patients with essential arterial hypertension, 68 hypertensives (47 men and 21
      women, mean age 59.4 +/- 9.5 years) without other cardiovascular disorders were
      studied. All patients underwent M-mode and two-dimensional echocardiogram and 24
      h ambulatory electrocardiographic monitoring to measure left ventricular internal
      dimension, septum and posterior wall thickness, left ventricular mass index,
      premature ventricular beats and modified Lown grade. Premature ventricular beats
      (PVB) and modified Lown grade were significantly related to left ventricular mass
      index, but not to left ventricular internal dimension, fractional shortening,
      systolic and diastolic blood pressure. There was no relation between age and
      number of PVB, or severity of arrhythmias. In conclusion, in hypertensive
      patients only left ventricular hypertrophy, and not age, plays a significant role
      in the pathophysiology of the increased incidence of ventricular arrhythmias by a
      different mechanism than age-related increased ventricular arrhythmias.

PMID- 7562890
TI  - Relation of sodium-lithium countertransport activity to markers of cardiovascular
      risk in normotensive subjects.
AB  - A study was undertaken in 298 normotensive, normolipidaemic and normoglycaemic
      subjects to define the range of erythrocyte sodium-lithium countertransport
      activity in this cohort and to determine the associations between
      countertransport activity and markers of vascular risk. Countertransport activity
      showed a positively skewed non-normal distribution with a median (95% confidence
      interval) of 0.197 (0.123-0.271) mmol Li/L erythrocytes per hour.
      Countertransport activity was elevated in women who were taking oral
      contraceptives (median (95% CI) mmol Li/L erythrocytes per hour, 0.270 (0.162
      0.320) vs. 0.147 (0.110-0.201)). Countertransport activity was also found to be
      elevated in subjects who had alcohol intakes greater than the recommended weekly
      maximum (median (95% CI) mmol Li/L erythrocytes per hour, 0.193 (0.139-0.211) vs.
      0.260 (0.148-0.317)). Positive correlations with sodium-lithium countertransport
      activity were noted with resting diastolic blood pressures (n = 298; P = 0.004)
      and maximal systolic blood pressure at peak exercise (n = 123; P = 0.003). In
      respect of serum biochemical variables, positive correlations were only found
      with triglycerides (P = 0.025) and creatinine (P = 0.005). These results support
      the view that elevation of erythrocyte sodium-lithium countertransport activity
      may reflect an alteration in the behaviour of cell membrane proteins through the
      influence of environmental factors associated with vascular risk.

PMID- 7562891
TI  - The continuing challenge of hypertension--bridging the gap between theory and
      practice. Proceedings of an international symposium. Barcelona, Spain, 28-29
      October 1994.

PMID- 7562892
TI  - Managing hypertension in general practice: can we do better?
AB  - Two surveys of hypertension treatment in Europe have revealed major differences
      between doctor perception, patient belief and the reality of BP control. The
      first survey (part of the Cardiomonitor Study) investigated 23,339 cardiovascular
      patients treated by 1471 doctors in Italy, Spain, France, the UK and Germany. The
      second survey researched attitudes to treatment among 301 general practitioners
      and 300 patients in Italy, France and the UK. Cardiomonitor revealed that
      hypertension was poorly controlled, with only 37% of patients achieving target
      BP. In contrast, the second survey revealed that doctors believed that target BP
      was reached in the majority (76%) of their treated patients with hypertension,
      while an even higher percentage of patients (95%) believed their BP to be well
      controlled. There were significant discrepancies in the perceived reasons for
      treatment failure between doctors and patients. Most doctors considered poor
      compliance with therapy to be the main reason for failure to achieve target BP.
      In contrast, most patients reported good compliance, blaming poor efficacy or
      side-effects for treatment failure. Objective studies suggest that compliance is
      lower than patients report and can be reduced by factors that affect quality of
      life, such as side-effects of treatment, complex dosing regimens, changes in
      therapy and concern about poorly controlled disease. This argues for effective,
      well-tolerated antihypertensive drugs that can be taken once daily, enabling
      quality of life to be maintained throughout treatment.

PMID- 7562893
TI  - Limiting factors in the control of BP: why is there a gap between theory and
      practice?
AB  - The benefits of BP reduction are undisputed, and management guidelines are well
      established. Nevertheless, epidemiological studies and randomised clinical trials
      have consistently shown that, although treated, BP frequently remains
      inadequately controlled. This failure to control BP adequately is not fully
      recognised by physicians or their patients. Furthermore, even when BP control is
      not achieved, there is evidence that many physicians do little to modify therapy.
      This gap between theory and practice in the control of hypertension is a
      multifactorial phenomenon. Patients may not take medication or adhere to their
      physician's advice; physicians appear satisfied with sub-optimal therapy; the
      underlying pathophysiology of hypertension is heterogeneous and thus it can be
      difficult to predict which patients will respond to a specific treatment; there
      is poor communication between physicians and their patients; and treatment
      guidelines may be too complex, theoretical and unclear to be followed in general
      practice. Despite these difficulties, it is clear that BP control can be improved
      by combining several antihypertensive drugs. This requires careful consideration
      with regard both to the mechanisms of action of the agents selected and their
      tolerability.

PMID- 7562894
TI  - What are the implications for the community of the discrepancy between the theory
      and practice of BP control?
AB  - Epidemiological data suggest that the lower the BP, the lower the cardiovascular
      risk. This is true across a broad range of BP levels, including those considered
      'normal'; more than half of all cardiovascular events attributed to raised BP
      occur when DBP is < or = 95 mmHg. The belief that lowering BP too far is harmful
      is based on the hypothesis of a J-shaped relationship between BP and risk of
      cardiovascular disease. The weight of evidence now clearly suggests, however,
      that the J-shaped curve is not a consequence of treatment, but of underlying
      cardiovascular dysfunction that reduces BP and increases morbidity and mortality.
      Current prospective observational data give no evidence of a threshold BP below
      which there is no further reduction in cardiovascular disease risk. The average
      BP reductions in randomised trials are 5-6 mmHg (diastolic) and 10-12 mmHg
      (systolic), which would be expected to reduce the incidence of stroke by 35% and
      of coronary heart disease by 21%. If average BP reductions were doubled,
      prospective observational studies suggest the cardiovascular risk would be
      reduced by a further 15-20%.

PMID- 7562895
TI  - Improving the management of hypertension in clinical practice.
AB  - Antihypertensive therapy is unquestionably beneficial, but current management of
      hypertension does not reduce cardiovascular risk to normotensive levels.
      Treatment of the hypertensive patient may be improved by a number of measures.
      These include control of SBP as well as DBP, with reduction to < 140/90 mmHg.
      Treatment of concomitant diseases and of other risk factors is likely to be of
      benefit, as is 24 h control of BP. Variability of BP appears to influence
      clinical outcome, but it is unclear whether this can be reduced by treatment.
      Poor patient compliance with treatment instructions may be an important factor in
      disappointing therapeutic performance, but could be improved with less complex
      treatment regimens.

PMID- 7562896
TI  - The hidden truth: what do the clinical trials really tell us about BP control?
AB  - Prospective observational studies show clearly that the risks of stroke, coronary
      heart disease and premature death are related directly to BP. Furthermore, the
      results of prospective, randomised intervention studies indicate that effective
      BP control reduces these risks. Although the number of patients being treated for
      hypertension has approximately doubled in the last 20 years, premature morbidity
      and mortality remain higher than in the normotensive population. This may relate
      to the inadequate level of BP control achieved in many patients. Two large
      studies have shown that DBP can be reduced to < 90 mmHg in almost all patients if
      antihypertensive therapy is intensified, and preliminary evidence suggests that
      this can be done without increasing the incidence of side-effects. The level to
      which BP should be reduced to achieve an optimum reduction in cardiovascular
      morbidity and mortality is currently being investigated in the Hypertension
      Optimal Treatment (HOT) Study.

PMID- 7562897
TI  - The heterogeneity of hypertension: why doesn't every patient respond to every
      antihypertensive drug?
AB  - Hypertension is a multifactorial disease, and there is growing evidence that
      implicates a range of environmental factors in its aetiology. These include
      dietary sodium, obesity, alcohol and stress. Additionally, several genetic
      abnormalities may predispose an individual to hypertension. The number of
      hypertensive phenotypes resulting from different environmental-genetic
      interactions may explain, therefore, why there is marked heterogeneity in
      response to treatment and why any single antihypertensive agent would be unlikely
      to control BP in more than 25-50% of patients. This is one rationale for
      combination therapies in which the component drugs affect different
      pathophysiological mechanisms.

PMID- 7562898
TI  - Improving the therapeutic balance between efficacy and tolerability in
      antihypertensive drugs--the rationale and benefits of combining felodipine and
      metoprolol.
AB  - Several studies, most recently the Starnberg Study on Epidemiology of
      Parkinsonism and Hypertension in the Elderly (STEPHY), have shown that BP is not
      adequately controlled in a substantial proportion of treated hypertensive
      patients. This finding highlights the need for new treatment strategies that are
      sufficiently effective throughout the dosing interval, well tolerated, and
      available in a convenient, once-daily regimen. Monotherapy with any individual
      drug class is often unable to fulfil all of these criteria in more than a
      minority of patients. In contrast, once-daily therapy with rational combinations
      of antihypertensive drugs offers a promising approach to improving treatment of
      hypertension. The highly vascular selective calcium antagonist felodipine and the
      cardioselective beta-blocker metoprolol have complementary mechanisms of action,
      making them appropriate for use together in the management of hypertension. A new
      extended-release (ER) formulation, combining felodipine, 5 mg, and metoprolol, 50
      mg*, has therefore been developed. This formulation has been shown to provide
      significantly greater reductions and higher antihypertensive response rates than
      either agent used alone. This high efficacy is achieved with maintained good
      tolerability. In comparative trials, felodipine-metoprolol has also been shown to
      be more effective than combination treatment with nifedipine and atenolol, or
      captopril and hydrochlorothiazide. It is concluded that the felodipine-metoprolol
      ER tablet offers predictably high 24 h antihypertensive response rates from a
      convenient and well-tolerated once-daily dose.

PMID- 7562899
TI  - A felodipine-metoprolol extended-release tablet: its properties and clinical
      development.
AB  - The current failure of antihypertensive therapy to control BP in many
      hypertensive patients highlights the need for new treatment strategies. Ideally,
      these new strategies should provide reliable, effective 24 h BP control in all
      types of patients with a convenient, well-tolerated regimen. Logimax, an extended
      release tablet containing felodipine and metoprolol, has been developed, which
      provides more effective control of BP in a wider range of patients than either
      component as monotherapy, without compromising tolerability. This combination
      increases the likelihood of achieving target BP and is therefore likely to
      provide further reductions in cardiovascular risk.

PMID- 7562900
TI  - The continuing challenge of hypertension.

PMID- 7562901
TI  - Management guidelines for hypertension: is anyone taking notice?
AB  - A number of national bodies and the World Health Organisation/International
      Society of Hypertension have published guidelines on the treatment of
      hypertension, and there is reasonable consensus between them. Repeated and
      accurate BP measurements are an essential starting point in the clinical
      management of hypertension. In mild-to-moderate hypertension, non-pharmacological
      treatments should always be instituted and their impact evaluated before drugs
      are considered. The recommended diastolic threshold for initiation of drug
      therapy varies between 90 and 100 mmHg and the systolic threshold lies between
      140 and 160 mmHg. There is also agreement that this threshold should be reduced
      to 140/90 mmHg when multiple risk factors co-exist. The generally accepted aim of
      treatment is to reduce DBP to < 90 mmHg, but there is controversy about lowering
      it further to < 80 mmHg. There is convincing evidence that elderly patients
      benefit most from treatment. It is also clear that treated patients with
      inadequately controlled BP remain at high risk of premature cardiovascular death.
      This highlights the need for guidelines that are suitable for routine use in
      clinical practice.

PMID- 7562902
TI  - Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity
      relationships and therapeutic applications.

PMID- 7562904
TI  - Synthesis of 1,4,7,8,9,10-hexahydro-9-methyl-6-nitropyrido[3,4-f]- quinoxaline
      2,3-dione and related quinoxalinediones: characterization of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (and N-methyl-D-aspartate) receptor
      and anticonvulsant activity.
AB  - Four related series of substituted quinoxalinediones containing angular fused
      piperidine rings have been synthesized as alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor antagonists with potential as
      neuroprotective agents, primarily for acute therapy immediately following a
      stroke. The compounds were tested for their affinity to the AMPA, kainate, and
      strychnine-insensitive glycine receptor sites. In AMPA binding, the most potent
      compound was 27a (PNQX, IC50 = 63 nM), with affinity comparable to the literature
      standard 1 (NBQX, IC50 = 52 nM). Other 6-nitro analogs from the 9-aza series had
      comparable affinity at the AMPA receptor, as did 6-nitro-8-aza derivatives such
      as 13a (iPNQX, IC50 = 290 nM). The receptor binding profile of 27a differed from
      that of 1 in that 27a possessed significant affinity at the glycine site of the N
      methyl-D-aspartate (NMDA) receptor, whereas 1 was essentially inactive. Three
      compounds, 26c, 26d, and 26e, demonstrated moderate selectivity for kainate
      relative to AMPA receptors. Selected analogs reported herein as well as in the
      literature were superimposed to generate an AMPA pharmacophore model, and 6
      substituted compounds from the PNQX and iPNQX series were combined and analyzed
      via quantitative structure-activity relationship techniques. Compounds with high
      affinity at non-NMDA receptors were further characterized in functional assays in
      neuronal cell culture and in a cortical wedge preparation. Both 1 and 27a showed
      comparable effectiveness in an AMPA- and kainate-induced excitoxicity assay. Both
      inhibited AMPA-induced depolarizations in the cortical wedge. However, 27a also
      inhibited spontaneous epileptiform discharges in the cortical wedge (reversed by
      glycine), while 1 was ineffective. The combination of AMPA and NMDA antagonist
      activity may contribute to the 30-fold difference in potency between 27a and 1 in
      the maximal electroshock convulsant assay in mice. The significant in vivo
      potency of 27a suggests that it has potential clinical utility.

PMID- 7562903
TI  - 1-Aminoindan-1,5-dicarboxylic acid: a novel antagonist at phospholipase C-linked
      metabotropic glutamate receptors.

PMID- 7562905
TI  - Potent and orally active angiotensin II receptor antagonists with equal affinity
      for human AT1 and AT2 subtypes.
AB  - In order to block the effects induced by the interactions between angiotensin II
      (AII) and both AT1 and AT2 receptors, we have pursued the discovery of orally
      active non-peptide AII antagonists that exhibit potent and equal affinity for
      human AT1 and AT2 receptor subtypes. A series of previously prepared nanomolar
      (IC50) trisubstituted 1,2,4-triazolinone biphenyl-sulfonamide dual-acting AII
      antagonists has been modified at five different positions in order to increase
      AT2 binding affinity, maintain AT1 activity, and reduce the human adrenal AT2/AT1
      potency ratio (IC50 ratio) from > or = 10. The targeted human adrenal potency
      ratio of < or = 1 was achieved with a number of compounds possessing an ethyl
      group at C5 of the triazolinone and a 3-fluoro substituent at the N4-biarylmethyl
      moiety. The most favored of these was compound 44 which exhibited subnanomolar
      potency at both the AT1 (rabbit aorta) and AT2 (rat midbrain) receptors, with a
      slight preference for the latter, and had a human adrenal AT2/AT1 IC50 ratio of
      1. This tert-butyl sulfonylcarbamate with an N2-[2-bromo-5-(valerylamino)phenyl]
      substituent had excellent iv activity at 1 mg/kg (100% peak inhibition, > or = 4
      h duration of action) and is orally active at 3 mg/kg with > 6 h duration of
      action in a conscious rat model. The present study shows that the NH of the amide
      on the N2-aryl moiety is not required for subnanomolar binding affinity to either
      receptor subtype, although a keto functionality at this position is essential for
      acceptable AT2 binding. Receptor-ligand binding interactions derived from the
      structure-activity relationships are discussed with respect to both receptor
      subtypes.

PMID- 7562907
TI  - New spiropiperidines as potent and selective non-peptide tachykinin NK2 receptor
      antagonists.
AB  - The synthesis of a series of 2-(5-fluoro-1H-indol-3-yl)ethyl spiropiperidines is
      described together with their tachykinin NK2 receptor affinities measured in a
      rat colon binding assay. Equivalent NK2 receptor binding affinity was observed
      for the spirooxazolidinone 3-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-1-oxa-3,8
      diazaspiro[4.5] decan-2-one (3a), the imidazolidinone 3-benzyl-8-[2-(5-fluoro-1H
      indol-3-yl)ethyl]-1,3,8-triazaspiro[4.5 ] decan-2-one (3s), and the pyrrolidinone
      2-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-2,8-diazaspiro[4.5]decan -3 - one
      (3t). Substitution in the phenyl ring of compound 3a produced no significant
      enhancement in NK2 binding affinity. Replacement of the phenyl ring in 3a with
      other aromatic rings resulted in a significant loss in binding affinity. Compound
      3a was shown to be a potent NK2 receptor antagonist in guinea pig trachea where
      it also demonstrated 1000-fold selectivity for NK2 receptors over NK1. In the
      anesthetized guinea pig, compound 3a administered by the intravenous or oral
      route displayed potent and long-lasting antagonist activity against NK2 receptor
      agonist induced bronchoconstriction.

PMID- 7562906
TI  - Derivatives of 5-[[1-(4'-carboxybenzyl)imidazolyl]methylidene]hydantoins as
      orally active angiotensin II receptor antagonists.
AB  - A series of 5-[[1-(4'-carboxybenzyl)imidazolyl]methylidene]hydantoins have been
      prepared and evaluated as in vitro and in vivo angiotensin II (Ang II)
      antagonists. Variation of substituents on the hydantoin ring leads to potent and
      selective Ang II antagonists with nanomolar IC50 values at the AT1 receptor and
      negligible affinity for the AT2 receptor. Preferred substituents include an n
      butyl at R1 and an alkyl or heteroarylmethyl substituent at R2. The selection of
      the R2 substituent was guided in part by the calculation of its log P since a
      significant correlation was observed between CLOGP and AT1 binding affinity. The
      biphenyl tetrazole pharmacophore, common to a number of AT1 antagonists, could be
      replaced by, for example, a 4-carbomethoxyphenyl substituent resulting in potent
      Ang II antagonists both in vitro and in vivo. A representative compound of this
      series is 57, which reduced the mean arterial blood pressure of renal
      hypertensive rats by 40% at 30 mg/kg po and by 25% at 10 mg/kg po. In addition
      this compound was efficacious in the salt-deplete normotensive monkey model
      maximally decreasing blood pressure 27% at 10 mg/kg po. In summary, these
      compounds belong to a novel class of Ang II antagonists that lack the biphenyl
      tetrazole moiety yet display appreciable and long lasting oral activity.

PMID- 7562908
TI  - Tyrosine kinase inhibitors. 7. 7-Amino-4-(phenylamino)- and 7-amino-4
      [(phenylmethyl)amino]pyrido[4,3-d]pyrimidines: a new class of inhibitors of the
      tyrosine kinase activity of the epidermal growth factor receptor.
AB  - The synthesis of 7-aminopyrido[4,3-d]pyrimidines bearing aromatic side chains at
      the 4-position is reported. These compounds are shown to be a new class of
      inhibitors of the tyrosine kinase activity of the epidermal growth factor
      receptor (EGFR). Structure-activity relationships (SARs) for substitution in both
      4-(phenylamino)- and 4-[(phenylmethyl)amino] side chains were determined, using a
      series of substituents (NO2, Br, CF3, OMe, NH2, and NMe2) selected primarily for
      their wide range of electronic properties. In the phenylamino series, 3
      substituted derivatives were more potent than the corresponding 2- and 4
      substituted analogues. For the 3-substituted compounds, activity was favored by
      electron withdrawal, in a relationship which could be quantified, with the 3-Br
      being the most potent compound (IC50 = 0.01 microM compared with IC50 = 0.34
      microM for the unsubstituted side chain derivative). No such correlation was
      apparent for the 2- or 4-substituent, although Br was still the best substituent.
      In contrast, in the 4-[(phenylmethyl)amino] series, substitution of the side
      chain was not beneficial. For the 4-(phenylamino) series, the substituent SARs
      are broadly similar to that found previously for 4-(phenylamino)quinazolines.
      These results suggest that side chain SARs may be broadly invariant over a range
      of different chromophores, with the side chain of choice for optimization of EGFR
      inhibitory activity being 4-[(3-bromophenyl)amino].

PMID- 7562909
TI  - Synthesis, antitumor activity, and chemical properties of silaplatin and related
      platinum (II) and platinum (IV) complexes derived from beta-silyl amines.
AB  - Platinum (II) and platinum (IV) coordination complexes derived from beta-silyl
      substituted amines were prepared. The solubility of selected complexes in water
      and physiological saline was measured, and the effect of the beta-silicon on the
      reactivity of the complex in aqueous solution was determined by HPLC. The
      stabilities of selected silyl complexes were compared to the carbon analogues.
      The cyclic complexes 2a ("silaplatin") and its Pt(IV) analogue, 2b, were very
      active against L1210 leukemia in vivo. Both the platinum (II) complex 2a and the
      platinum (IV) complex 2b produced a significant number of cures over the dose
      range 10-40 mg/kg. The platinum (II) complex 2a, silaplatin, was very active in
      vivo against an L1210 leukemia subline that was resistant to cisplatin; 2a was
      also active, when given ip, against ic implanted L1210. The
      cyclobutanedicarboxylic acid complex 3c was synthesized; this complex was active
      against both cisplatin sensitive and resistant L1210 leukemia but was less potent
      than the analogous dichloro compound 2a. The acyclic platinum (II) and platinum
      (IV) complexes 1a,b were synthesized and unexpectedly found to be inactive in
      vivo against L1210 leukemia. More lipophilic silaplatin analogues were prepared-
      Pt(II) complex 2c and Pt(IV) complex 2d have one additional methylene carbon
      compared to 2a,b, whereas Pt(II) complex 2e and Pt(IV) complex 2f have two
      additional methylene carbons. Cyclization of the alkyl groups attached to the
      silicon gave the spiro bicyclic Pt(II) complexes 10a and 11a and the Pt(IV)
      complexes 10b and 11b.

PMID- 7562910
TI  - Effect of bridge region variation on antifolate and antitumor activity of
      classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines.
AB  - Variation of the bridge linking the heterocyclic ring and p-aminobenzoyl-L
      glutamate portions of our previously described classical 2,4-diaminofuro[2,3
      d]pyrimidines 1 and 2 are reported as inhibitors of dihydrofolate reductase
      (DHFR) and thymidylate synthase (TS) and as antitumor agents. Specifically 
      CH2CH2- and -CH2NHCH2- bridged analogues, N-[4-[2-(2,4-diaminofuro[2,3
      d]pyrimidin-5-yl) ethyl]benzoyl]-L-glutamic acid (3) and N-[4-[[N-[(2,4
      diaminofuro[2,3-d]pyrimidin-5-yl) methyl]amino]methyl]benzoyl]-L-glutamic acid
      (4), respectively, were synthesized. Compound 3 was obtained via a Wittig
      reaction of the tributylphosphonium salt of 2,4-diamino-5-(chloromethyl)furo[2,3
      d]pyrimidine (5) and methyl 4-formylbenzoate (6) followed by reduction and
      coupling with the diethyl ester of L-glutamic acid. Compound 4 was synthesized by
      the nucleophilic displacement of 5 with diethyl N-[4-(aminomethyl)benzoyl]-L
      glutamate (15) and saponification. Both analogues were evaluated in vitro as
      inhibitors of DHFRs from (recombinant) human, human CCRF-CEM cells, and
      Lactobacillus casei. Compound 3 showed moderate activity (IC50 10(-6)-10(-7) M).
      Compound 4 was essentially inactive (IC50 10(-5) M, CCRF-CEM). The compounds were
      also evaluated against TS from (recombinant) human and L. casei and were of low
      activity (IC50 10(-5) M). The three-atom-bridged analogue 4 was somewhat more
      inhibitory to human TS than methotrexate (MTX). Compound 3 inhibited the growth
      of tumor cells in culture (IC50 10(-7) M) while 4 showed a low level of growth
      inhibitory activity. The inhibition of the growth of leukemia CCRF-CEM cells by
      both compounds parallels their inhibition of CCRF-CEM DHFR. Analogue 3 was a good
      substrate for human folylpolyglutamate synthetase (FPGS) derived from CCRF-CEM
      cells (Km 8.5 microM). Further evaluation of the growth inhibitory activity of 3
      against the MTX-resistant subline of CCRF-CEM cells (R30dm) with decreased FPGS
      indicated that poly-gamma-glutamylation was important for its action. Protection
      studies with 3 in the FaDu squamous cell carcinoma cell line indicated that
      inhibition was completely reversed by leucovorin [(6R,S-5-formyltetrahydrofolate]
      or by a combination of thymidine and hypoxanthine, suggesting an antifolate
      effect directed at DHFR.

PMID- 7562911
TI  - Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by
      geldanamycin and dihydrogeldanamycin derivatives.
AB  - The erbB-2 oncogene encodes a transmembrane protein tyrosine kinase which plays a
      pivotal role in signal transduction and has been implicated when overexpressed in
      breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin
      antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found
      to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3
      cells in culture. Chemistry efforts to modify selectively the quinoid moiety of
      GDM afforded derivatives with greater potency in vitro and in vivo. Analogs
      demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after
      systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells
      transfected with human erbB-2 (FRE/erbB-2). Specifically, dosed intraperitoneally
      at 100 mg/kg, 17-(allylamino)-17-demethoxygeldanamycin and other 17-amino analogs
      were effective at reducing p185 phosphotyrosine in subcutaneous flank FRE/erbB-2
      tumors. Modifications to the 17-19-positions of the quinone ring revealed a broad
      structure-activity relationship in vitro.

PMID- 7562913
TI  - Novel cytotoxic 3'-(tert-butyl) 3'-dephenyl analogs of paclitaxel and docetaxel.
AB  - 3'-(tert-Butyl) 3'-dephenyl analogs of paclitaxel were synthesized from 10
      deacetylbaccatin III and oxazolidinecarboxylic acid 7 followed by acylation of
      intermediate amines 10 and 11. Oxazolidinecarboxylic acid 7 was prepared in five
      steps and in good overall yield from L-tert-leucine. Twelve analogs were
      synthesized and evaluated for their in vitro ability to stimulate the formation
      of microtubules and for their cytotoxicity against B16 melanoma cells. Amide,
      carbamate, urea, and thiourea congeners were prepared. The most potent
      derivatives found in this study are the docetaxel analog 13, the N-[(tert
      amyloxy)carbonyl] analog 17, and the 3'-phenylurea and 3'-tert-butylurea
      derivatives 20 and 23. Six of these analogs were shown to be ca. 90 times more
      soluble in water than paclitaxel and ca. 4-5 times more water-soluble than
      docetaxel.

PMID- 7562912
TI  - erbB-2 oncogene inhibition by geldanamycin derivatives: synthesis, mechanism of
      action, and structure-activity relationships.
AB  - Overexpression of the erbB-2 oncogene has been linked to poor prognosis in
      breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin
      antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found
      to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3
      cells in culture. Chemistry efforts to modify selectively the ansa ring of GDM
      afforded derivatives with greater potency in vitro and in vivo. Analogs
      demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after
      systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells
      transfected with human erbB-2. Functional group modification in the ansa ring was
      performed stereoselectively and regiospecifically without the need for protection
      strategies. Essential functional groups that were required for anti-erbB-2
      activity were the 7-carbamate and the 2,3-double bond. Modification of the
      functional groups at the other positions was permitted. Structure-activity
      relationships are described for 1-5-, 7-9-, 11-, 15-, and 22-substituted
      geldanamycins.

PMID- 7562914
TI  - Furanfurin and thiophenfurin: two novel tiazofurin analogues. Synthesis,
      structure, antitumor activity, and interactions with inosine monophosphate
      dehydrogenase.
AB  - The syntheses of furan and thiophene analogues of tiazofurin (furanfurin and
      thiophenfurin, respectively) are described. Direct stannic chloride-catalyzed C
      glycosylation of ethyl 3-furan-carboxylate (6) or ethyl 3-thiophencarboxylate
      (18) with 1,2,3,5-tetra-O-acetyl-D-ribofuranose gave 2- and 5-glycosylated
      regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5
      diglycosylated derivatives. Deprotection of ethyl 5-(2,3,5-tri-O-acetyl-beta-D
      ribofuranosyl)furan-3-carboxylate (9 beta) and ethyl 5-(2,3,5-tri-O-acetyl-beta-D
      ribofuranosyl)thiophene-3-carboxylate (20 beta) with sodium ethoxide afforded
      ethyl 5-beta-D-ribofuranosylfuran-3-carboxylate (12 beta) and ethyl 5-beta-D
      ribofuranosylthiophene-3-carboxylate (23 beta) which were converted into 5-beta-D
      ribofuranosylfuran-3-carboxamide (furanfurin, 4) and 5-beta-D
      ribofuranosylthiophene-3-carboxamide (thiophenfurin, 5) by reaction with ammonium
      hydroxide. The anomeric configuration and the site of glycosylation were
      established by 1H-NMR and proton-proton nuclear Overhauser effect difference
      spectroscopy. The structure of compound 23 beta was confirmed by X-ray
      crystallography. Thiophenfurin was found to be cytotoxic in vitro toward murine
      lymphocytic leukemia P388 and L1210, human myelogenous leukemia K562, human
      promyelocytic leukemia HL-60, human colon adenocarcinoma LoVo, and B16 melanoma
      at concentrations similar to that of tiazofurin. In the same test furanfurin
      proved to be inactive. Thiophenfurin was found active in vivo in BD2F1 mice
      inoculated with L1210 cells with a % T/C of 168 at 25 mg/kg. K562 cells
      incubation with thiophenfurin resulted in inhibition of inosine monophosphate
      (IMP) dehydrogenase (63%) and an increase in IMP pools (6-fold) with a concurrent
      decrease in GTP levels (42%). Incubation of adenosine-labeled K562 cells with
      tiazofurin, thiophenfurin, and furanfurin resulted in a 2-fold higher NAD
      analogue formulation by thiophenfurin than by tiazofurin. Furanfurin was
      converted to the NAD analogue with only 10% efficiency. The results obtained
      support the hypothesis that the presence of S in the heterocycle in position 2
      with respect to the glycosidic bond is essential for the cytotoxicity and IMP
      dehydrogenase activity of tiazofurin, while the N atom is not.

PMID- 7562915
TI  - Synthesis and structure-activity relationships of analogs of 2'-deoxy-2'-(3
      methoxybenzamido)adenosine, a selective inhibitor of trypanosomal glycosomal
      glyceraldehyde-3-phosphate dehydrogenase.
AB  - In continuation of a project aimed at the structure-based design of drugs against
      sleeping sickness, analogs of 2'-deoxy-2'-(3-methoxybenzamido)adenosine (1) were
      synthesized and tested to establish structure-activity relationships for
      inhibiting glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Compound
      1 was recently designed using the NAD:GAPDH complexes of the human enzyme and
      that of Trypanosoma brucei, the causative agent of sleeping sickness. In an
      effort to exploit an extra hydrophobic domain due to Val 207 of the parasite
      enzyme, several new 2'-amido-2'-deoxyadenosines were synthesized. Some of them
      displayed an interesting improvement in inhibitory activity compared to 1.
      Carbocyclic or acyclic analogs showed marked loss of activity, illustrating the
      importance of the typical (C-2'-endo) puckering of the ribose moiety. We also
      describe the synthesis of a pair of compounds that combine the beneficial effects
      of a 2- and 8-substituted adenine moiety on potency with the beneficial effect of
      a 2'-amido moiety on selectivity. Unfortunately, in both cases, IC50 values
      demonstrate the incompatibility of these combined modifications. Finally,
      introduction of a hydrophobic 5'-amido group on 5'-deoxyadenosine enhances the
      inhibition of the protozoan enzyme significantly, although the gain in
      selectivity is mediocre.

PMID- 7562916
TI  - Inhibition of uridine phosphorylase: synthesis and structure-activity
      relationships of aryl-substituted 5-benzyluracils and 1-[(2-hydroxyethoxy)methyl]
      5-benzyluracils.
AB  - A series of 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils were synthesized and
      tested for inhibition of murine liver uridine phosphorylase (UrdPase). Inhibitors
      of UrdPase are reported to enhance the chemotherapeutic utility of 5-fluoro-2'
      deoxyuridine and 5-fluorouracil and to ameliorate zidovudine-induced anemia in
      animal models. We prepared a series of 5-aryl-substituted analogues of 5
      benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 microM), to
      develop a compound with enhanced potency and improved pharmacokinetics. The first
      phase of structure-activity relationship studies on a series of 32 aryl
      substituted 5-benzyluracils found several 5-(3-alkoxybenzyl) analogues of 5
      benzyluracil with enhanced potency. The acyclovir side chain, the (2
      hydroxyethoxy)methyl group, was substituted on the more potent aryl-substituted 5
      benzyluracils. The two most potent compounds, 10y (3-propoxy) and 10dd (3-sec
      butoxy), were inhibitors of UrdPase with IC50s of 0.047 and 0.027 microM,
      respectively. Six compounds were tested in vivo for effects on steady-state
      concentrations of circulating uridine in rats. Plasma uridine levels were
      elevated 3-9-fold by compound levels that ranged from 8 to 50 microM.

PMID- 7562918
TI  - Quantitative structural activity relationship study of bis-tetraazacyclic
      compounds. A novel series of HIV-1 and HIV-2 inhibitors.
AB  - This work describes a study of quantitative structural activity relationships
      (QSAR) of bis-tetraazamacrocyclic compounds. These compounds represent a novel
      class of very potent and selective anti-HIV inhibitors, with a new mode of
      action. The QSAR study correlates structural features of the compounds with anti
      HIV activity, resulting in a model which has a high predictive capacity
      (predictive r2 = 0.79). This predictive model will be of major importance for the
      design of new anti-HIV inhibitors of this class. Use is made of partial least
      squares (PLS) analysis, with the novelty being that structural features derived
      by inclusion of all sterically allowed conformations for each molecule are
      included in the analysis. PLS analysis was made of descriptors, including
      structural parameters, macrocyclic ring size, metal chelating ability, etc., and
      those features necessary for the observed antiviral activities of these compounds
      were deduced from the models. Since all sterically allowed conformations are
      included in the analysis, the flexibility of the molecules is also taken into
      account. In addition, a correlation is found (indicated by a predictive r2 value
      of 0.61) between inhibition of HIV-1 (HIV-2) and syncytium formation inhibition
      in the presence of bis-cyclam analogues, leading to the suggestion of a common
      target, namely, gp120, being involved in both inhibition of virus replication and
      syncytium formation.

PMID- 7562917
TI  - 1-Phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes and related derivatives as
      ligands for the neuromodulatory sigma 3 receptor: further structure-activity
      relationships.
AB  - A series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl-3
      aminotetralins, PATs) previously was found to stimulate tyrosine hydroxylase
      activity and dopamine synthesis in rat brain through interaction with a novel
      sigma 3 receptor. Specifically, the trans-1R,3S-(-) isomer of H2-PAT showed
      highest affinity for sigma 3 receptors and also produced maximal stimulation of
      tyrosine hydroxylase activity and dopamine synthesis, as compared to the trans
      1S,3R-(+) isomer. Affinity for sigma 3 receptors and functional potency at
      stimulating dopamine synthesis were attenuated either by altering the position or
      dimethyl substitution pattern of the amino group or by hydroxylating the tetralin
      aromatic ring. A preliminary binding model can accommodate many PAT analogs and
      several non-PATs with a wide range of affinities for the sigma 3 receptor. Here,
      we report the synthesis and evaluation of additional analogs in order to expand
      previous structure-activity relationship studies. Further molecular modifications
      include synthesis of 1-phenyl-1-methyl-3-amino, 1-phenyl-2-amino, 1-phenyl-3
      (trimethylammoniumyl), and 1-phenyl-3-(phenylalkyl) analogs, as well as ring
      expanded tetrahydrobenzocycloheptenes. In general, the above modifications
      decreased sigma 3 receptor affinity and, in some cases, caused a reversal of the
      sigma 3 binding selectivity of trans- versus cis-PATs found previously. Most
      analogs were selective for sigma 3 receptors and showed little or no affinity for
      either sigma 1/sigma 2 or dopamine D1, D2, and D3 receptors. N-Phenylalkyl
      substituents, such as N-phenylethyl, however, endowed the 1-phenyl-3
      aminotetralins with enhanced sigma 1/sigma 2 and dopamine receptor affinity while
      decreasing sigma 3 affinity, thus abolishing sigma 3 selectivity.

PMID- 7562919
TI  - Inhibition of monoamine oxidase-B by 5H-indeno[1,2-c]pyridazines: biological
      activities, quantitative structure-activity relationships (QSARs) and 3D-QSARs.
AB  - A large series (66 compounds) of indeno[1,2-c]pyridazin-5-ones (IPs) were
      synthesized and tested on their monoamine oxidase-A (MAO-A) and MAO-B inhibitory
      activity. All of the tested compounds acted preferentially on MAO-B displaying
      weak (nonmeasurable IC50 values) to high (submicromolar IC50 values) activities.
      The most active compound was p-CF3-3-phenyl-IP (IC50 = 90 nM). Multiple linear
      regression analysis of the substituted 3-phenyl-IPs yielded good statistical
      results (q2 = 0.74; r2 = 0.86) and showed the importance of lipophilic,
      electronic, and steric properties of the substituents in determining inhibitory
      potency. Various comparative molecular field analysis studies were performed with
      different alignments and including the molecular lipophilicity potential. This
      led to a model including the steric, electrostatic and lipophilicity fields and
      having a good predictive value (q2 = 0.75; r2 = 0.93).

PMID- 7562921
TI  - A new paclitaxel photoaffinity analog with a 3-(4-benzoylphenyl)propanoyl probe
      for characterization of drug-binding sites on tubulin and P-glycoprotein.

PMID- 7562922
TI  - Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase
      2 inhibition.
AB  - The antiinflammatory activity of a series of 2-substituted- and 2,3-disubstituted
      4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was previously shown
      by quantitative structure-activity relationship (QSAR) studies to be correlated
      with the molar refractivity and inductive field effect of the 2-substituent and
      the lipophilicity of the 3-substituent. The present study demonstrates that much
      of the antiinflammatory activity of these pyrroles could be correlated with the
      inhibition of the inducible isoform of cyclooxygenase (COX2). Additional QSAR
      studies have been used to identify the molecular parameters necessary for
      maximizing COX2 inhibition while simultaneously minimizing the inhibition of
      constitutively expressed cyclooxygenase-1. Such an effort should facilitate the
      discovery and development of selective COX inhibitors that should lead to safer
      nonsteroidal antiinflammatory drugs.

PMID- 7562920
TI  - Synthesis and anticonvulsant activity of N-benzylpyrrolo[2,3-d]-, -pyrazolo[3,4
      d]-, and -triazolo[4,5-d]pyrimidines: imidazole ring-modified analogues of 9-(2
      fluorobenzyl)-6-(methylamino)-9H-purine.
AB  - Analogues of 9-(2-fluorobenzyl)-6-(methylamino)-9H-purine (1) containing
      isosteric replacements of the imidazole ring atoms were synthesized and tested
      for anticonvulsant activity. The pyrrolo[2,3-d]-, pyrazolo[3,4-d]-, and
      triazolo[4,5-d]pyrimidines were less active than 1 against maximal electroshock
      induced seizures (MES) in rats when given po. The differences in anti-MES
      activity for these analogues was not explained by differences in pKa or
      lipophilicity. However, the four classes of heterocycles have distinctly
      different calculated electrostatic isopotential maps, which may be related to
      optimum anticonvulsant activity.

PMID- 7562923
TI  - Pyrazinoic acid esters with broad spectrum in vitro antimycobacterial activity.
AB  - A series of substituted pyrazinoic acid esters has been prepared and examined for
      their in vitro activity against Mycobacterium avium and Mycobacterium kansasii as
      well as Mycobacterium tuberculosis. Modification of both the pyrazine nucleus and
      the ester functionality have been very successful in expanding the activity of
      pyrazinamide to include M. avium and M. kansasii, organisms normally not
      susceptible to pyrazinamide. Several of these compounds have activities 100-1000
      fold greater than that of pyrazinamide against M. tuberculosis.

PMID- 7562924
TI  - Resolution and in vitro and initial in vivo evaluation of isomers of iodine-125
      labeled 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)
      alpha-phenylacetate: a high-affinity ligand for the muscarinic receptor.
AB  - 1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)- alpha
      phenylacetate (IQNP, 1), is a highly selective ligand for the muscarinic
      acetylcholinergic receptor (mAChR). There are eight stereoisomers in the racemic
      mixture. The optical isomers of alpha-hydroxy-alpha-phenyl-alpha-(1-propyn-3
      yl)acetic acid were resolved as the alpha-methylbenzylamine salts, and the
      optical isomers of 3-quinuclidinol were resolved as the tartrate salts. The E and
      Z isomers were prepared by varying the reaction conditions for the stannylation
      of the triple bond followed by purification utilizing flash column
      chromatography. In vitro binding assay of the four stereoisomers containing the
      (R)-(-)-3-quinuclidinyl ester demonstrated that each isomer of 1 bound to mAChR
      with high affinity. In addition, (E)-(-)-(-)-IQNP demonstrated the highest
      receptor subtype specificity between the m1 molecular subtype (KD, nM, 0.383 +/-
      0.102) and the m2 molecular subtype (29.6 +/- 9.70). In vivo biodistribution
      studies demonstrated that iodine-125-labeled (E)-(-)-(+)-1 cleared rapidly from
      the brain and heart. In contrast, iodine-125-labeled (E)-(-)-(-)-, (Z)-(-)-(-)-,
      and (Z)-(-)-(+)-1 have high uptake and retention in mAChR rich areas of the
      brain. It was also observed that (E)-(-)-(-)-IQNP demonstrated an apparent
      subtype selectivity in vivo with retention in M1 (m1, m4) mAChR areas of the
      rain. In addition, (Z)-(-)-(-)-IQNP also demonstrated significant uptake in
      tissues containing the M2 (m2) mAChR subtype. These results demonstrate that the
      iodine-123-labeled analogues of the (E)-(-)-(-)- and (Z)-(-)-(-)-IQNP isomers are
      attractive candidates for single-photon emission-computed tomographic imaging of
      cerebral and cardiac mAChR receptor densities.

PMID- 7562926
TI  - Novel 4'-substituted and 4',4"-disubstituted 3 alpha-(diphenylmethoxy)tropane
      analogs as potent and selective dopamine uptake inhibitors.
AB  - A series of 4'-substituted and 4',4"-disubstituted 3 alpha
      (diphenylmethoxy)tropane analogs were prepared as novel probes for the dopamine
      transporter. These compounds were evaluated in radiolabeled binding assays for
      the dopamine, norepinephrine, and serotonin transporters. All of these compounds
      monophasically displaced [3H]WIN 35,428 binding in rat caudate putamen with Ki
      values ranging from 11.8 to 2000 nM. The most potent compound in this series was
      4',4"-difluoro 3 alpha-(diphenylmethoxy)tropane 7c with a Ki = 11.8 nM. All of
      the compounds inhibited dopamine uptake in rat caudate putamen (IC50 = 24-4456
      nM) which correlated significantly (r = 0.907; p > 0.0001) with binding
      affinities at the dopamine transporter. None of the compounds demonstrated high
      affinity binding at the norepinephrine (Ki > 4800 nM) or serotonin (Ki > 690 nM)
      transporters. Therefore, the most potent dopamine uptake inhibitors in this
      series were highly selective for the dopamine transporter. Preliminary behavioral
      studies of several of these analogs (7a-e) suggested that the compounds did not
      display a cocaine-like behavioral profile, despite their ability to inhibit
      dopamine uptake. The present data coupled with the observed differences from
      cocaine in structure-activity relationships suggested that the 3 alpha
      (diphenylmethoxy)tropane analogs may be interacting at a different active site
      than cocaine on the dopamine transporter and that an additional binding domain
      might be exploited for the identification of potential therapeutics for the
      treatment of cocaine abuse.

PMID- 7562927
TI  - Mononucleoside phosphotriester derivatives with S-acyl-2-thioethyl bioreversible
      phosphate-protecting groups: intracellular delivery of 3'-azido-2',3'
      dideoxythymidine 5'-monophosphate.
AB  - The synthesis, in vitro anti-HIV-1 activity, and decomposition pathways of
      several mononucleoside phosphotriester derivatives of 3'-azido-2',3'
      dideoxythymidine (AZT) incorporating a new kind of carboxylate esterase-labile
      transient phosphate-protecting group, namely, S-acyl-2-thioethyl, are reported.
      All the described compounds showed marked antiviral activity in thymidine kinase
      deficient CEM cells in which AZT was virtually inactive. The results strongly
      support the hypothesis that such pronucleotides exert their biological effects
      via intracellular delivery of the 5'-mononucleotide of AZT. This point was
      corroborated by decomposition studies in cell extracts and culture medium.

PMID- 7562929
TI  - Synthesis and anti-DNA viral activities in vitro of certain 2,4-disubstituted-7
      (2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d d pyrimidine nucleosides.
AB  - Several novel 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D-
      arabinofuranosyl)pyrrolo[2,3-d]pyrimidines have been synthesized and evaluated
      for their anti-human cytomegalovirus (HCMV), anti-hepatitis B virus (HBV), and
      anti-herpes simplex virus (HSV) activities in vitro. These nucleosides were
      prepared starting from 2-amino-4-chloro-7-(2-deoxy-2-fluoro- 3,5-di-O-benzoyl
      beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (3), which in turn was
      synthesized by direct glycosylation of the sodium salt of 2-amino-4
      chloropyrrolo[2,3-d]pyrimidine (1) with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D
      arabinofuranosyl bromide (2). Displacement of the 4-chloro group of 3 with OH,
      NH2, NHOH, SH, and SeH nucleophiles furnished the corresponding nucleosides 6-8,
      12, and 14, respectively. The 3'-deoxygenation of 2-amino-4-chloro-7- (2-deoxy-2
      fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (4) and subsequent
      amination gave 2,4-diamino-2',3'-dideoxy derivative 19. Catalytic hydrogenation
      of 3 followed by debenzoylation afforded 2-aminopyrrolo[2,3-d]pyrimidine
      nucleoside 23. Among the compounds evaluated for their ability to inhibit the
      growth of HCMV (strain AD169) in MRC-5 cells using a plaque reduction assay, only
      7 was significantly active in vitro with a 50% inhibitory concentration (IC50) of
      3.7 micrograms/mL (TI > 125), whereas the IC50 value of ganciclovir (DHPG) was
      3.2 micrograms/mL. Strain D16 of HCMV was more resistant to 7 (IC50 11
      micrograms/mL) than the AD169 strain. When 7 was tested in combination with DHPG,
      the resultant anti-HCMV activity was found to be moderately synergistic with no
      evidence of antagonism. Nucleoside 7 also reduced episomal HBV replication in
      human hepatoblastoma 2.2.15 cells with an IC50 of 0.7 micrograms/mL (TI > 143).
      Development of cells harboring HBV which had become resistant to the drug was not
      observed with 7. Compound 7 also exhibited significant activity against herpes
      simplex virus types 1 and 2 (IC50 of 4.1 and 6.3 micrograms/mL, respectively) in
      Vero cells.

PMID- 7562930
TI  - Pseudodipeptide inhibitors of protein farnesyltransferase.
AB  - A series of pseudodipeptide amides are described that inhibit Ras protein
      farnesyltransferase (PFTase). These inhibitors are truncated versions of the C
      terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for
      PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics
      previously reported, these inhibitors do not have a C-terminal carboxyl moiety,
      yet they inhibit farnesylation in vitro at < 100 nM. Despite the absence of the X
      residue in the CAAX motif, which normally directs prenylation specificity, these
      pseudodipeptides are greater than 100-fold selective for PFTase over type 1
      protein geranylgeranyltransferase.

PMID- 7562925
TI  - Synthesis and antifungal activity of new azole derivatives containing an N
      acylmorpholine ring.
AB  - A series of azole derivatives carrying an N-acylmorpholine ring are described.
      The compounds were chemically designed to simulate the lanosterol D ring, taking
      advantage of the conformational preferences of 2-alkyl-1-acylmorpholines. Three
      structural variables, the nature of the N-benzoyl group, the phenyl substituents,
      and the degree of oxidation at carbon 2 of the morpholine, were optimized for
      maximum activity. Only the (5R,6R) isomers showed antifungal activity. Cyclic
      hemiacetal (-)-39a (UR-9746) and cyclic ether (-)-41 (UR-9751) were selected for
      further development. In vitro, (-)-41 was clearly more active than (-)-39a and
      somewhat less active than the acyclic counterpart (-)-7. In vivo activity was
      assessed by a systemic (mouse) and a vaginal (rat) candidosis model. In the
      former, (-)-39a, (-)-41, and (-)-7 at 1 mg/kg given 1, 4, and 24 h postinfection
      displayed 90-100% protection from mortality on day 9. Compound (-)-39a was
      slightly more potent than (-)-41 and similar in potency to (-)-7. The three
      compounds were superior in potency to fluconazole and similar in potency in SCH
      42427 in this test. In the vaginal model, (-)-39a and (-)-41 given daily during 3
      days after infection at 0.5 mg/kg showed high levels of protection on days 10 and
      15. At 0.25 mg/kg, (-)-39a was slightly more potent than SCH-42427 and (-)-7 and
      superior in potency to (-)-41 and fluconazole in this model. Preliminary 28-day
      toxicity tests at 100 mg/kg/day po in rats indicated no or very mild adverse
      effects for the two UR compounds.

PMID- 7562928
TI  - Chiral dioxolane inhibitors of leukotriene biosynthesis: structure-activity
      relationships and syntheses using asymmetric dihydroxylation.
AB  - 1,3-Dioxolanes have been described as chiral inhibitors of 5-lipoxygenase (5LO).
      In the present work, this series has been developed further to provide agents
      which showed comparable or superior potency in vivo to ZD2138, a
      methoxytetrahydropyran inhibitor of 5LO, which is currently undergoing clinical
      evaluation. An asymmetric synthesis was developed to these dioxolanes based on
      asymmetric dihydroxylation. (S)-N-Methyl-4'-[[4-(2,2,4- trimethyl-1,3-dioxolan-4
      yl)thien-2-yl]thio]acetanilide ((S)-10d) inhibited leukotriene B4 (LTB4)
      synthesis in A23187-stimulated human whole blood in vitro with IC50 0.039 microM,
      25-fold more potent than (R)-10d. In vivo, (S)-10d inhibited LTB4 synthesis by
      70% in zymosan-inflamed air pouch exudate in rat 10 h after an oral dose of 1.5
      mg/kg. Structure-activity relationship considerations suggested that the
      dioxolane and methoxytetrahydropyran series are related, a conclusion which can
      be supported by molecular modeling.

PMID- 7562931
TI  - Peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In
      vitro and in vivo potency of a series of peptidyl alpha-ketobenzoxazoles.
AB  - A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for
      their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These
      compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl
      carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the
      benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a
      variety of substituents which spanned a range of physicochemical properties had
      only a modest effect on in vitro potency (Ki = 3-0.4 nM). This apparent lack of a
      significant effect is believed to result from the fact that any increased ketone
      carbonyl activation by the ring substituent is counter balanced by a
      corresponding decrease in the hydrogen-bonding ability of the benzoxazole
      nitrogen atom. In contrast to the results in vitro, maximizing in vivo activity
      was critically dependent upon the choice of the benzoxazole ring substituent.
      Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE
      induced lung injury when administered intratracheally 24 h prior to the enzyme.

PMID- 7562932
TI  - Cyclization-activated prodrugs: N-(substituted 2-hydroxyphenyl and 2
      hydroxypropyl)carbamates based on ring-opened derivatives of active
      benzoxazolones and oxazolidinones as mutual prodrugs of acetaminophen.
AB  - N-(Substituted 2-hydroxyphenyl)- and N-(substituted 2-hydroxypropyl)carbamates
      based on masked active benzoxazolones (model A) and oxazolidinones (model B),
      respectively, were synthesized and evaluated as potential drug delivery systems.
      A series of alkyl and aryl N-(5-chloro-2-hydroxyphenyl)carbamates 1 related to
      model A was prepared. These are open drugs of the skeletal muscle relaxant
      chlorzoxazone. The corresponding 4-acetamidophenyl ester named chlorzacetamol is
      a mutual prodrug of chlorzoxazone and acetaminophen. Chlorzacetamol and two other
      mutual prodrugs of active benzoxazolones and acetaminophen were obtained in a two
      step process via condensation of 4-acetamidophenyl 1,2,2,2-tetrachloroethyl
      carbonate with the appropriate anilines. Based on model B, two mutual prodrugs of
      acetaminophen and active oxazolidinones (metaxalone and mephenoxalone) were
      similarly obtained using the appropriate amines. All the carbamate prodrugs
      prepared were found to release the parent drugs in aqueous (pH 6-11) and plasma
      (pH 7.4) media. The detailed mechanistic study of prodrugs 1 carried out in
      aqueous medium at 37 degrees C shows a change in the Bronsted-type relationship
      log t1/2 vs pKa of the leaving groups ROH: log t1/2 = 0.46pKa-3.55 for aryl and
      trihalogenoethyl esters and log t1/2 = 1.46pKa-16.03 for alkyl esters. This
      change is consistent with a cyclization mechanism involving a change in the rate
      limiting step from formation of a cyclic tetrahedral intermediate (step k1) to
      departure of the leaving group ROH (step k2) when the leaving group ability
      decreases. This mechanism occurs for all the prodrugs related to model A.
      Regeneration of the parent drugs from mutual prodrugs related to model B takes
      place by means of a rate-limiting elimination-addition reaction (E1cB mechanism).
      This affords acetaminophen and the corresponding 2-hydroxypropyl isocyanate
      intermediates which cyclize at any pH to the corresponding oxazolidinone drugs.
      As opposed to model A, the rates of hydrolysis of mutual prodrugs of model B
      clearly exhibit a catalytic role of the plasma. It is concluded from the plasma
      studies that the carbamate substrates can be enzymatically transformed into
      potent electrophiles, i.e., isocyanates. In the case of the present study, the
      prodrugs are 2-hydroxycarbamates for which the propinquity of the hydroxyl
      residue and the isocyanate group enforces a cyclization reaction. This
      mechanistic particularity precludes their potential toxicity in terms of potent
      electrophiles capable of modifying critical macromolecules.

PMID- 7562933
TI  - Novel deltorphin heptapeptide analogs with potent delta agonist, delta
      antagonist, or mixed mu antagonist/delta agonist properties.
AB  - A series of deltorphin (DLT: Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) analogs in which
      Leu5 and/or Met6 were mainly replaced by t-Leu(Tle) and/or N alpha-alkylated
      glycine were synthesized and examined for their receptor binding properties and
      in vitro bioactivities by guinea pig ileum (GPI) and mouse vas deferens (MVD)
      assays. [Tle5]DLT(2) showed a dramatic decrease in the MVD potency when compared
      to the parent peptide and was found to have a potent delta receptor antagonist
      activity against various delta agonists with Ke values of 16-311 nM.
      Interestingly, the antagonist potency of 2 against DPDPE as agonist was 20-fold
      weaker than that against deltorphins or Leu-enkephalin. Among the analogs in
      which Met6 was replaced by an N alpha-alkylated Gly residue, [N alpha-isobutyl
      Gly6]DLT(5) behaved as a mixed mu antagonist/delta agonist while its isomeric
      analogs in which the N alpha-alkyl is n-butyl (4) or (R or S) sec-butyl (6a,b)
      were very potent delta receptor agonists. Analogs 2, 4, 6a, and 6b were highly
      stable against rat brain and rat plasma enzymes and thus may represent a starting
      point for the development of novel receptor-specific compounds useful as ligands
      for studies of opioid receptors.

PMID- 7562934
TI  - Ribose-modified adenosine analogues as potential partial agonists for the
      adenosine receptor.
AB  - We have adopted a practical three-step route for the synthesis of 2'- and 3'
      deoxy analogues of N6-substituted adenosines: protection of the hydroxyl groups,
      replacement of the N6-amino by a better leaving group, and combined deprotection
      and N6-amination in the last step. This route was used to synthesize deoxy
      analogues of CPA, CHA, and R- and S-PIA. The compounds were tested on the
      adenosine A1 and A2a receptors in our search for partial agonists for these
      receptors. The GTP shift was used as an in vitro measure for the intrinsic
      activity of these compounds; the in vivo intrinsic activities of the deoxy
      analogues of CPA and R-PIA were determined in the rat cardiovascular system.
      Thus, it was shown that the hydroxyl groups are determinants for the affinity and
      intrinsic activity of these analogues. Removal of the 2'- and 3'-hydroxyl groups
      affects affinity and intrinsic activity, whereas removal of the 5'-hydroxyl group
      decreases only affinity.

PMID- 7562935
TI  - Synthesis and antiviral activity of 8-aza analogs of chiral [2-(phosphonomethoxy)
      propyl]guanines.
AB  - (R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza
      PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus
      (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2
      (phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the
      alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(
      )[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by
      deprotection of the phosphonic moiety. A different, even more convenient
      synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)
      pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also
      reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the
      MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding
      S enantiomers were found to be less potent. When evaluated in combination with
      AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic
      anti-HIV-1 effects, respectively.

PMID- 7562936
TI  - Synthesis of tight binding inhibitors and their action on the proprotein
      processing enzyme furin.
AB  - Furin is a subtilisin-like eukaryotic serine endoprotease which processes
      proproteins to biologically active proteins and peptides. Also, the envelope
      proteins of viruses, such as influenza and HIV viruses, need to be processed by
      furin for infectivity. This enzyme has a consensus substrate specificity for Arg
      Xxx-Lys/Arg-Arg at the cleavage site. Two kinds of transition state analog
      peptides were designed and tested in vitro with furin. The ketomethylene series,
      psi (COCH2), have Ki's in the submicromolar range; the aminomethyl aminomethyl
      ketone series, psi(COCH2NH), have Ki's in the nanomolar range. The best inhibitor
      is Dec-Arg-Val-Lys-Arg-CH2-Ala-Val-Gly-NH2 (2c) with a Ki of 3.4 nM.

PMID- 7562938
TI  - New antihistamines: substituted piperazine and piperidine derivatives as novel H1
      antagonists.
AB  - Structural manipulation of polycyclic piperazinyl imide serotonergic agents led
      to the synthesis of compound 8, 2-[4-[4-[bis(4-fluorophenyl)methyl]-1
      piperazinyl]-4, 4a,5,5a,6,6a-hexahydro-4,6-ethenocycloprop[f]isoindole-1,3(2H,3
      aH)-dione, which demonstrated good H1-antagonist activity. Substitution of a
      xanthinyl moiety for the polycyclic imide group led to the identification of
      novel xanthinyl-substituted piperazinyl and piperidinyl derivatives with potent
      antihistamine H1-activity without the undesirable antidopaminergic activity of 8.
      One compound, 24, 7-[3-[4-(diphenylmethoxy)-1-piperidinyl]propyl]- 3,7-dihydro
      1,3-dimethyl-1H-pyrine-2,6-dione (WY-49051), is a potent, orally active H1
      antagonist with a long duration of action and a favorable central nervous system
      profile.

PMID- 7562937
TI  - Synthesis and biological evaluation of N6-cycloalkyl derivatives of 1
      deazaadenine nucleosides: a new class of anti-human immunodeficiency virus
      agents.
AB  - A series of 1-deazaadenine nucleosides with the N6 nitrogen unsubstituted or
      bearing methyl or cycloalkyl substituents, with or without a chloro group in the
      2-position, and with the glycosylic moiety being ribose (1-16), 2'-deoxyribose
      (17-32), or 2', 3'-dideoxyribose (33-48) were designed and synthesized starting
      from 5,7-dichloro-3H-imidazo[4,5-b] pyridine (50). These compounds were evaluated
      for their in vitro activity against human immunodeficiency virus type-1 (HIV-1)
      and herpes simplex virus type-1 (HSV-1). In addition they were tested for their
      ability to inhibit adenosine deaminase (ADA) from calf intestine. While the
      parent compounds 1-deazaadenosine (9), 2'-deoxy-1-deazaadenosine (25), and 2',3'
      dideoxy-1- deazaadenosine (41) and the corresponding 2-chloro derivatives were
      inactive, nucleosides bearing cycloalkyl substituents on N6 exhibited moderate to
      good anti-HIV-1 activity, compared to 2',3'-dideoxyadenosine, with the degree and
      pattern of improvement depending on the structure of the sugar moiety. In
      general, 2'-deoxy- and 2',3'-dideoxy derivatives were more potent compounds than
      the corresponding ribose nucleosides. Compounds bearing a 6-cycloheptyl or
      cyclooctylamine were the most active in every series. The presence of a chloro
      group in the 2-position improved both activity and therapeutic index in every
      series, the most active compound being 2'-deoxy-2-chloro-N6-cycloheptyl-1
      deazaadenosine (23; ED50 = 0.2 microM). On the other hand, most of these
      derivatives were inactive as anti-HSV-1 agents, showing a high degree of virus
      selectivity. The 1-deazaadenine derivatives were not substrates of adenosine
      deaminase, and some of them proved to be good inhibitors of the enzyme. However,
      the ADA inhibitory activity does not account for the antiviral potency since
      increased lipophilicity and steric hindrance of substituents resulted in
      derivatives much less active than the parent compounds.

PMID- 7562939
TI  - Synthesis and anticonvulsant activity of enaminones. 3. Investigations on 4'-, 3'
      , and 2'-substituted and polysubstituted anilino compounds, sodium channel
      binding studies, and toxicity evaluations.
AB  - In a continuing evaluation of the aniline-substituted enaminones, the synthesis
      of additional para-substituted analogs has been made in an attempt to further
      quantify the electronic (sigma) and lipophilic (pi) requirements for
      anticonvulsant activity in this series. In addition, meta- and ortho-substituted
      and polysubstituted compounds have been synthesized and evaluated for
      anticonvulsant activity. In the para-substituted series, 4-cyano analogs (32 and
      33) (+ sigma, - pi), which were highly active via intraperitoneal (ip) injection
      in mice, were inactive on oral (po) administration in rats. The para-substituted
      trifluoromethoxy (+ sigma, + pi) analog (8) had significant potency by both
      routes. Meta substitution limited the activity due to steric factors. Bromo and
      iodo substituents produced active para-substituted analogs (5 and 17) but were
      inactive when substituted in the meta position (37 and 41, respectively). Ortho
      substitution provided no clear relationship due to nonparametric deviations.
      Neither 1, the prototype enaminone, nor 2, the putative metabolite, produced
      significant nephrotoxicity or hepatotoxicity. Sodium channel binding of 1 and 8
      indicated that 8 displayed relatively potent sodium channel binding but 1 showed
      weaker effects with IC50 values of 489 and 170 microM respectively against
      [3H]batrachotoxinin A 20 alpha-benzoate ([3H]BTX-B).

PMID- 7562941
TI  - Design, synthesis, and structure-activity relationships of a new series of alpha
      adrenergic agonists: spiro[(1,3-diazacyclopent-1-ene)-5,2'-(1',2',3',4'-
      tetrahydronaphthalene)].
AB  - The contractions induced by a partial alpha 1-adrenoceptor agonist in cutaneous
      veins, such as the saphenous vein, show a particular sensitivity to changes in
      local temperature: the contractility to a partial alpha 1-adrenoceptor agonist
      increases when the temperature is raised, a response that contrasts to that noted
      with full alpha 1- and alpha 2-adrenoceptor agonists. This observation may be of
      importance for the treatment of the symptoms of venous insuffiency, favored
      during warm summer days. A new series of full and partial alpha-adrenergic
      agonists was designed and synthesized, the spiro[(1,3-diazacyclopent-1-ene)-5,2'
      (1',2',3',4'- tetrahydronaphthalene)] 7a-kk or spiro-imidazolines. Using in vitro
      (femoral artery and saphenous vein) and in vivo (pithed rat) biological
      evaluations, structure-activity relationships could be defined which allowed the
      discovery of a full alpha 2-agonist (34b), a full alpha 1-agonist (7s), and a
      nonselective partial alpha 1/alpha 2-agonist (7aa) endowed with an outstanding
      veinotonic selectivity as compared to its effect on mean arterial pressure. The
      latter compound is presently undergoing extensive pharmacological and
      toxicological evaluations, as a clinical candidate.

PMID- 7562940
TI  - Characterization of potent and selective antagonists at postsynaptic 5-HT1A
      receptors in a series of N4-substituted arylpiperazines.
AB  - Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl
      chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to
      obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From
      the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4
      benzodioxin-5-yl)piperazine (3a) was chosen as a model of an arylpiperazine in
      view of its selectivity for 5-HT1A receptors versus alpha 1-, alpha 2-, and beta
      adrenergic receptors, as well as dopamine D1 and D2 receptors. Two other closely
      related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1
      (benzofuran-7-yl)piperazine (3c), were also examined in this study. All compounds
      showed high affinity at 5-HT1A sites (8.10 < or = pKis < or = 9.35), and the
      majority behaved as antagonists in vivo in blocking the hypothermia induced by
      the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at
      equivalent doses. An in vivo evaluation of dopamine D2 receptor antagonist
      properties revealed that the majority of compounds was devoid of activity at this
      site, in marked contrast to BMY 7378 which displayed virtually no selectivity for
      5-HT1A versus dopamine D2 receptors. Moreover, six compounds of the present
      series, 8, 10, 11, 14, 25, and 37, showed > 10-fold selectivity in vitro for 5
      HT1A versus alpha 1-adrenergic receptors. Compound 14 displayed an optimal
      compromise between potency (pKi = 8.75), marked antagonist activity, and
      selectivity toward alpha 1-adrenergic (81-fold) and dopamine D2 (195-fold)
      receptors. These characteristics clearly distinguish 14 from previously-reported
      ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial
      agonist NAN 190 which, in contrast to the compounds of this series, belong to the
      well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The
      availability of 14 (S 15535) should facilitate the further elucidation of the
      functional role and potential therapeutic significance of 5-HT1A receptors.

PMID- 7562942
TI  - Synthesis, X-ray crystallography, and pharmacokinetics of novel azomethine
      prodrugs of (R)-alpha-methylhistamine: highly potent and selective histamine H3
      receptor agonists.
AB  - Since various neuroregulatory functions of the histamine H3 receptor have been
      proved during the last few years, the H3 receptor is of current interest.
      Azomethine derivatives of the highly potent histamine H3 receptor agonist (R)
      alpha-methylhistamine (1) were prepared as lipophilic prodrugs to improve the
      bioavailability of the hydrophilic drug, particularly its entry into the brain.
      Additionally, azomethine derivatization provides protection against histamine
      methyltransferase, the major metabolizing enzyme in man, and thus efficiently
      enhances the bioavailability of 1. The molecular conformations of (R)-2(-)[[N(
      )[1-(1H-imidazol-4-yl)-2-propyl]- imino]phenylmethyl]phenol (9a) and (R)-4-fluoro
      2(-)[[N(-)[1-(1H-imidazol-4-yl)-2-propyl[imino]- (4-chlorophenyl)methyl]phenol
      (9p) were determined by X-ray structure analysis. An intramolecular hydrogen bond
      which is essential for the stability of these azomethines was thereby confirmed.
      Moreover, the pharmacokinetic parameters of the prodrugs were investigated in
      vitro as well as in vivo. The halogenated azomethines have an effect following
      peroral administration in mice, and some of them seem to be highly potent for the
      central nervous system (CNS) delivery of 1. At present the most potent prodrug of
      1 is (R)-4-chloro-2(-)[[N(-)[1-(1H-imidazol-4-yl)-2-propyl]imino](4-
      chlorophenyl)methyl]phenol (9q), reaching by far the highest CNS level of 1 (Cmax
      = 71 ng/g). Prodrugs of this type are not only valuable pharmacological tools but
      may also become H3 histaminergic drugs for therapeutic use.

PMID- 7562943
TI  - A molecular dynamics approach to receptor mapping: application to the 5HT3 and
      beta 2-adrenergic receptors.
AB  - A molecular dynamics-based approach to receptor mapping is proposed, based on the
      method of Rizzi (Rizzi, J. P.; et al. J. Med. Chem. 1990, 33, 2721). In Rizzi's
      method, the interaction energy between a series of drug molecules and probe atoms
      (which mimic functional groups on the receptor, such as hydrogen bond donors) was
      calculated. These interactions were calculated on a three-dimensional grid within
      a molecular mechanics parameters, were placed at these minima. The distances
      between the dummy atom sites were monitored during molecular dynamics simulations
      and plotted as distance distribution functions. Important distances within the
      receptor became apparent, as drugs with a common mode of binding share similar
      peaks in the distance distribution functions. In the case of specific 5HT3
      ligands, the important donor--acceptor distance within the receptor has a range
      of ca. 7.9--8.9 A. In the case of specific beta 2-adrenergic ligands, the
      important donor--acceptor distances within the receptor lie between ca. 7--9 A
      and between 8 and 10 A. These distances distribution functions were used to
      assess three different models of the beta 2-adrenergic G-protein-coupled
      receptor. The comparison of the distance distribution functions for the
      simulation with the actual donor--acceptor distances in the receptor models
      suggested that two of the three receptor models were much more consistent with
      the receptor-mapping studies. These receptor-mapping studies gave support for the
      use of rhodopsin, rather than the bacteriorhodopsin template, for modeling G
      protein-coupled receptors but also sounded a warning that agreement with binding
      data from site-directed mutagenesis experiments does not necessarily validate a
      receptor model.

PMID- 7562945
TI  - Design, synthesis, and antiviral activity of certain 2,5,6-trihalo-1-(beta-D
      ribofuranosyl)benzimidazoles.
AB  - A new series of 2-substituted 5,6-dichlorobenzimidazole ribonucleosides has been
      synthesized and tested for activity against two human herpes viruses and for
      cytotoxicity. 2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) was
      prepared by ribosylation of the heterocycle 2,5,6-trichlorobenzimidazole followed
      by a removal of the protecting groups. The 2-bromo derivative (BDCRB) was made in
      a similar fashion from 2-bromo-5,6-dichlorobenzimidazole. In contrast, the 2-iodo
      derivative presented a more difficult problem since the appropriate heterocycle
      was unavailable. This prompted us to prepare the 2-amino derivative followed by
      nonaqueous diazotization and removal of the blocking groups. Biological
      evaluation revealed marked differences in the activities of these compounds and
      the closely related known compound 5,6-dichloro-1-(beta-D
      ribofuranosyl)benzimidazole (DRB). DRB was weakly active against both human
      cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), (IC50's = 42 and
      30 microM, respectively) but was cytotoxic to uninfected human foreskin
      fibroblasts and KB cells in the same dose range. Similar results were obtained
      with the heterocycle 2,5,6-trichlorobenzimidazole. In marked contrast, the
      ribonucleoside of 2,5,6-trichlorobenzimidazole (TCRB) was active against HCMV
      (IC50 = 2.9 microM, plaque assay; IC90 = 1.4 microM, yield assay) but only weakly
      active against HSV-1 (IC50 = 102 microM, plaque assay). Little to no cytotoxicity
      was observed in HFF and KB cells at concentrations up to 100 microM. By changing
      the substituent at the 2-position from chlorine to bromine (BDCRB), a 4-fold
      increase in activity against HCMV was observed without any significant increase
      in cytotoxicity. In contrast, the 2-I and 2-NH2 derivatives were only weakly
      active against HCMV and HSV-1 with activity not well-separated from cytotoxicity.
      These data establish that for maximum activity against HCMV with separation from
      cytotoxicity, ribose is preferred at the 1-position and that Cl or Br is
      apparently preferred at the 2-position. The activity and selectivity of both TCRB
      and BDCRB were better than that observed with either ganciclovir or foscarnet.

PMID- 7562944
TI  - In vivo and in vitro studies on the neurotoxic potential of 6-hydroxydopamine
      analogs.
AB  - In an attempt to determine which physical and biological properties could best be
      correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)
      2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and
      compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in
      combination with the standard 1, include all eight of the 2,4,5-trisubstituted
      phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the
      substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high
      (300 nmol) intracerebroventricular doses of all analogs produced long-term (7
      day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of
      dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4
      dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective
      than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid
      method and Fink-Heimer silver degeneration stain, it was determined that overt
      neural degeneration was produced by 8. In vitro, the ease of oxidation of the
      eight analogs was found to be represented by a formal potential range of -130 to 
      212 mV vs SCE. However, there was no obvious relationship between ease of
      oxidation and the extent of monoamine depletion from mouse brain. Using kinetic
      analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the
      standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/-
      0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis
      was used to determine that differences in NE and DA depletion by each analog
      could not be explained by differences in potency for in vitro uptake blockade.
      However, there was a correlation between the Ki for [3H]NE uptake blockade and
      the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 =
      0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in
      vitro tests both reflect interaction with the same NE neuronal membrane transport
      site. A similar correlation between Ki and EC50 was shown for all eight analogs
      using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction
      with the same DA neuronal membrane transport site. These findings demonstrate
      that there is no single property that can account for selectivity of action
      and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

PMID- 7562948
TI  - Synthesis and antimalarial activities of several fluorinated artemisinin
      derivatives.
AB  - The carbonyl groups in several artemisinin derivatives were converted into
      geminal difluorinated compounds on treatment with diethylaminosulfur trifluoride.
      A number of other mono- and polyfluorinated artemisinin derivatives were
      prepared. Their in vitro antimalarial activities were all equal to or greater
      than the nonfluorinated analogs or precursors.

PMID- 7562946
TI  - Synthesis and antiproliferative and antiviral activity of 2'-deoxy-2'
      fluoroarabinofuranosyl analogs of the nucleoside antibiotics toyocamycin and
      sangivamycin.
AB  - The glycosylation of 3,4-dicyano-2-[(ethoxymethylene)amino]pyrrole (7) with 2
      deoxy-2-fluoro-alpha-D-erythro-pentofuranosyl bromide (2) furnished an anomeric
      mixture of nucleosides (8a,b). This mixture was separated, and the individual
      anomers were treated with methanolic ammonia to effect a concomitant deblocking
      and ring closure. This furnished both anomers of 2'-deoxy-2'-fluoro-ara
      toyocamycin (9a,b). The cyano moiety of 9b was converted to the carboxamide
      moiety to furnish 2'-deoxy-2'-fluoro-ara-sangivamycin (10) and to the
      thiocarboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-thiosangivamycin (11).
      The target compounds 10 and 11 showed similar antiproliferative activity against
      L1210 cells in vitro, with IC50's of 3 and 5 microM. Antiviral evaluation
      revealed a somewhat different pattern of activity. All analogs, both alpha and
      beta anomers, were active against human cytomegalovirus (HCMV), albeit the beta
      anomers were most active. The beta anomers also were active against herpes
      simplex virus type 1 (HSV-1) and human immunodeficiency virus (HIV). Compound 10
      was most active in the series, ca. 10-fold more potent than 11; IC50's for 10
      ranged from 4 to 25 nM for HCMV, HIV, and varicella zoster virus (VZV) and from
      30 to 500 nM for HSV-1. Even though compound 10 was cytotoxic, which will
      probably preclude its use as an antiviral drug (IC50's = 0.2-5.5 microM), the
      difference between cytotoxicity and activity against HCMV, HIV, and VZV was
      sufficient to indicate specific activity against a viral target.

PMID- 7562947
TI  - Synthesis and evaluation of certain thiosangivamycin analogs as potential
      inhibitors of cell proliferation and human cytomegalovirus.
AB  - A series of 7-substituted 4-aminopyrrolo[2,3-d]pyrimidines related to the
      nucleosides toyocamycin and thiosangivamycin were prepared and tested for their
      activity against human cytomegalovirus (HCMV). The nucleosides 2'
      deoxytoyocamycin (1), xylo-toyocamycin (2), 3'-deoxytoyocamycin (3), 2',3'
      dideoxy-2',3'-didehydrotoyocamycin (4), 2',3'-dideoxytoyocamycin (5), ara
      toyocamycin (6), 2'-deoxy-2'-amino-ara-toyocamycin (7), and 5'-deoxytoyocamycin
      (8) were treated with sodium hydrogen sulfide generated in situ to afford the
      corresponding thiosangivamycin analogs (9-16). The cyano derivatives 1-8 were
      synthesized by modifications of literature procedures. All of the thioamide
      derivatives (9-16) were active against HCMV with IC50's ranging from 0.5 to 6
      microM. Most also were active against herpes simplex virus type 1 (HSV-1) but at
      higher concentrations. The antiviral activity was not completely separated from
      cytotoxicity in two human cell lines. The antiproliferative activity was strongly
      influenced by the position of the modification on the carbohydrate moiety. The
      xylosyl and 3'-deoxy derivatives were significantly more potent than those with
      modifications at the 2', 5', or 2',3' position(s). Interestingly, 5'
      deoxythiosangivamycin (16) possessed both antiviral and antiproliferative
      activity suggesting that phosphorylation of the 5'-hydroxyl may not be required
      for these compounds to have biological activity.

PMID- 7562951
TI  - Probing the hydrophobic pocket of the active site of aromatase with 4-phenoxy-7
      alpha-(phenylthio)-4-androstene-3,17-dione.
AB  - In order to examine the nature of the hydrophobic pocket at the active site of
      aromatase, we carried out the synthesis, biochemical evaluation, and molecular
      modeling studies on 4-phenoxy-7 alpha-(phenylthio)-4-androstenedione 2. Aromatase
      inhibitory activity of 2 was found to be significantly weaker than that of the 4-
      and 7 alpha-mono(phenylthio)-substituted derivatives of androstenedione. These
      results along with those obtained from the modeling studies suggest the existence
      of a single hydrophobic pocket corresponding to the alpha-face in the C4, C6, C7
      region of androstenedione.

PMID- 7562949
TI  - Development of a potent thrombin receptor ligand.
AB  - The N-terminal thrombin receptor peptide H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp
      Lys-Tyr-Glu-Pro-Phe-OH (1) fully activates the thrombin receptor with an EC50 of
      10 microM. Structural features in the tetradecapeptide which are responsible for
      receptor activation have been elucidated. Agonist potency has been enhanced 1000
      fold with the design of the shortened peptide H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr-NH2
      (56). This analog exhibits an EC50 of 0.01 microM and is the most potent agonist
      for receptor activation reported to date. The monoiodinated derivative H-Ala
      Phe(p-F)-Arg-Cha-HArg-Tyr(3-I)-NH2 (59) exhibits an EC50 of 0.03 microM, a level
      sufficient for development of a radioligand.

PMID- 7562950
TI  - 1-(Fluorobenzyl)-4-amino-1H-1,2,3-triazolo[4,5-c]pyridines: synthesis and
      anticonvulsant activity.
AB  - A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for
      activity against maximal electroshock-induced seizures in rodents. The most
      promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a
      purine anticonvulsant, has a profile in rodents that suggests 14 will be free of
      emesis and useful in the treatment of seizure disorders for which phenytoin is
      presently indicated.

PMID- 7562952
TI  - Ah receptor involvement in mediation of pyruvate carboxylase levels and activity
      in mice given 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - The arylhydrocarbon receptor (AhR) plays a central role in mediating 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) toxicity in animals. The investigations
      described here provide evidence that support a role for the AhR in TCDD-mediated
      pyruvate carboxylase (PC) level/activity reductions in mice. Pyruvate carboxylase
      plays a pivotal role in gluconeogenesis and in supplying carbon units for the
      citric acid cycle. Delivered ip in a corn oil carrier, TCDD suppresses PC
      activity/amount at doses as low as 1 microgram/kg in responsive C57BL/6J(Ahb/b)
      mice. Corn oil alone injected ip into mice at 4 mL/kg appears to be an inducer
      that increases the amount and activity of PC. However, TCDD suppresses this
      induction. In the Ahb/b mouse, PC levels and activity are reduced to 10% of
      control values at a dose of 75 micrograms/kg. A time-course experiment shows that
      the PC reductions are apparent within 16 hours post-TCDD exposure. Here we report
      investigations on the PC/TCDD response using a congenic C57BL/6J(Ahd/d) mouse
      strain having an AhR with a low affinity for TCDD. If the PC/TCDD response is AhR
      mediated, the congenic mouse strain (Ahd/d) would require much higher doses of
      TCDD to suppress PC. In the Ahd/d mice, we observe that an approximately 60-fold
      increase in TCDD dose is necessary to produce a PC/TCDD effect. We also find that
      in Ahd/d mice, corn oil does not induce an increase in PC activity/amounts, as
      reported for Ahb/b mice.

PMID- 7562953
TI  - Lipoxygenase-mediated glutathione oxidation and superoxide generation.
AB  - Soybean lipoxygenase-mediated cooxidation of reduced glutathione (GSH) and
      concomitant superoxide generation was examined. The oxidation of GSH was
      dependent on the concentration of linoleic acid (LA), GSH, and the enzyme. The
      optimal conditions to observe maximal enzyme velocity included the presence of
      0.42 mM LA, 2 mM GSH, and 50 pmole of enzyme/mL. The GSH oxidation was linear up
      to 10 minutes and exhibited a pH optimum of 9.0. The reaction displayed a Km of
      1.49 mM for GSH and Vmax of 1.35 +/- 0.02 mumoles/min/nmole of enzyme. Besides
      LA, arachidonic and gamma-linolenic acids also supported the lipoxygenase
      mediated GSH oxidation. Hydrogen peroxide and 13-hydroperoxylinoleic acid
      supported GSH cooxidation, but to a very limited extent. Oxidized glutathione
      (GSSG) was identified as the major product of the reaction based on the depletion
      of nicotinamide-adenine dinucleotide 3'-phosphate (NADPH) in the presence of
      glutathione reductase. The GSH oxidation was accompanied by the reduction of
      ferricytochrome c, which can be completely abolished by superoxide dismutase
      (SOD), suggesting the generation of superoxide anion radicals. Under optimal
      conditions, the rate of superoxide generation (measured as the SOD-inhibitable
      reduction of ferricytochrome c) was 10 +/- 1.0 nmole/min/nmole of enzyme. These
      results clearly suggest that lipoxygenase is capable of oxidizing GSH to GSSG and
      simultaneously generating superoxide anion radicals, which may contribute to
      oxidative stress in cells under certain conditions.

PMID- 7562954
TI  - A kinetic analysis of hepatic microsomal activation of parathion and chlorpyrifos
      in control and phenobarbital-treated rats.
AB  - A kinetic analysis of cytochrome P450-mediated desulfuration (activation) or
      dearylation (detoxication) showed that rat hepatic microsomes have a greater
      capacity to detoxify and a lower capacity to activate chlorpyrifos compared to
      parathion. Kinetic curves for the desulfuration of both parathion and
      chlorpyrifos were biphasic; Kmapps of 0.23 and 71.3 microM were calculated for
      parathion, and 1.64 and 50.4 microM for chlorpyrifos. While phenobarbital (PB)
      exposure seemed to generally lower the Kmapps for desulfuration except for the
      low Km activity on chlorpyrifos, the results were not statistically significant.
      While the low Km activity contributed 44 and 60% of the control Vmax for
      parathion and chlorpyrifos, respectively, it contributed 50 and 17% in PB-treated
      rats. These studies have indicated the presence of a low Km activity capable of
      functioning at very low substrate concentrations. A single dearylation Kmapp was
      calculated, 56.0 and 9.8 microM for parathion and chlorpyrifos, respectively.
      Phenobarbital exposure seemed to raise the Kmapps of dearylation; however, again,
      the results were not statistically significant. While numerous biochemical
      factors contribute to the overall toxicity levels of phosphorothionate
      insecticides, the in vitro efficiencies of hepatic microsomal desulfuration and
      dearylation of parathion and chlorpyrifos correspond to the acute toxicity
      levels.

PMID- 7562955
TI  - Effect of thyroid hormone administration on the depletion of circulating
      glutathione in the isolated perfused rat liver and its relationship to
      basolateral gamma-glutamyltransferase activity.
AB  - The influence of thyroid hormone administration on liver glutathione (GSH)
      extraction in the isolated perfused liver was studied in fed rats for a period of
      1-7 days following a single dose of 0.1 mg 3,5,3'-triiodothyronine (T3)/kg. T3
      treatment led to an early and transient calorigenic response, as well as an
      enhancement in liver GSH removal, reaching a maximal effect at 2 days after
      hormone administration, which was normalized in the 3- to 7-day period studied.
      Addition of the gamma-glutamyltransferase (gamma-GT) inhibitor DL-serineborate (4
      mM) to the perfusate abolished the increase in the hepatic removal of GSH
      elicited by T3, and enhanced the sinusoidal concentration of GSH, studied at 2
      days after hormone administration. These data support the role of hepatic
      basolateral gamma-GT ectoactivity in the depletion of portally added and liver
      derived GSH as an adaptive response to recover GSH levels after reduction by T3
      induced oxidative stress.

PMID- 7562956
TI  - Toxicology of cupric salts on honeybees. IV--Gluconate and sulfate action on
      hemolymph trehalose activity in vivo and in vitro.
AB  - A biphasic increase of hemolymph glucose levels was observed following injection
      to bees of cupric gluconate or sulfate, both potent agents for the control of
      Varroa jacobsoni, a parasitic mite of hives. The simultaneous injection to bees
      of 0.3 microM BAYg5421 (an inhibitor of alpha-glucosidases) quenched the
      response, suggesting a direct effect of 2 nmol/bee cupric ions on trehaloses'
      activity. One nanomol of injected cupric gluconate increased the trehalose (Tre)
      activity by 233% in crude hemolymph extracts at 1 mM trehalose concentration, and
      exhibited biphasic dose-related effects with a maximum 15% increase at 0.5 mM
      cupric ion and a stabilized 20% inhibition from 4 mM, regardless of the anionic
      moiety. Upon partial purification of the enzyme complex, two fractions (FI = 75%
      and FII = 25% of total activity) were isolated that exhibited, respectively, less
      and more marked positive cooperatively than crude extract. Form I showed almost
      no susceptibility to either cupric derivatives, which indicated form II as the
      most likely target, with 68% and 72% increases with 0.25 mM cupric sulfate and
      0.5 mM cupric gluconate, in presence of 16 mM trehalose.

PMID- 7562957
TI  - Hepatic oxidative stress and related defenses during treatment of mice with
      acetylsalicylic acid and other peroxisome proliferators.
AB  - The peroxisome proliferators perfluorooctanoic acid (PFOA; 0.02% w/w),
      perfluorodecanoic acid (PFDA; 0.02%, w/w), nafenopin (0.125%, w/w), clofibrate
      (0.5%, w/w), and acetylsalicylic acid (ASA; 1%, w/w) were administered to male
      C57 BL/6 mice in their diet for two weeks. Parameters for Fe3+ ADP, NADPH or
      ascorbic acid-initiated lipid peroxidation in vitro were measured. Approximately
      a twofold increase in susceptibility to lipid peroxidation was obtained for all
      the peroxisome proliferators tested. Cotreatment of mice with the peroxisome
      proliferator ASA (1%, w/w) and a catalase inhibitor, 3-amino-1,2,4-triazole (AT;
      0.4%, w/w) for 7 days resulted in little inhibition of peroxisome proliferation,
      an elevated level of H2O2 in vivo, and total inhibition of the increased
      susceptibility to lipid peroxidation in vitro. No increase in lipid peroxidation
      in vivo was observed. Certain antioxidant enzymes (DT-diaphorase, superoxide
      dismutase, glutathione transferase, glutathione peroxidase, and glutathione
      reductase) and components (ubiquinone and alpha-tocopherol) were also measured.
      The results showed that there was some induction of these antioxidant enzymes and
      components by ASA or aminotriazole, except for glutathione peroxidase and
      superoxide dismutase, which were inhibited. The possible involvement of oxidative
      stress in the carcinogenicity of peroxisome proliferators is discussed.

PMID- 7562958
TI  - Evidence for two functionally distinct forms of the human Ah receptor.
AB  - The Ah receptor (AhR) was visualized using monoclonal antibody Rpt 1 on protein
      blots of HeLa cell cytosol; two bands were detected at 104 and 106 kDa. The
      photoaffinity ligand, 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin, was added
      to HeLa cells in culture, and after 1 hour the cells were UV irradiated.
      Cytosolic and high salt nuclear preparations were isolated and subjected to
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by
      transfer of the protein to membrane. The AhR was visualized on the membrane,
      revealing two bands. Alignment of an autoradiogram with the membrane revealed
      that only the 106 kDa (upper) band was photoaffinity labeled. The nuclear
      fraction contained only the photoaffinity-labeled 106 kDa form of the AhR. The
      104 kDa AhR does not appear to be a proteolytic product of the 106 kDa form.
      Cyanogen bromide fragmentation revealed that both forms contain the same size N
      terminal fragment. Sucrose density gradient analysis of HeLa cell cytosol
      indicated that both forms cosedimented at 9 S. Both the 106 and 104 kDa AhR bands
      were detected in four different human cell lines. Together, these results would
      indicate that the AhR in human cell lines exists in two distinct forms.

PMID- 7562959
TI  - HLA-B27 and spondyloarthropathy: value for early diagnosis?

PMID- 7562962
TI  - Emotional and functional impact of DNA testing on patients with symptoms of
      Huntington's disease.
AB  - The potential impact of DNA testing on asymptomatic subjects at risk for
      Huntington's disease (HD) has been addressed by numerous studies, but the effect
      of revealing the genetic results to patients with a clinically established
      diagnosis of HD has not been previously evaluated. We studied 36 patients, with
      equal distribution of men and women, mean age 53.9 (SD 12.3) years (range 25-76)
      and mean duration of symptoms of 11.2 (SD 7.7) years (range 2-33), whose clinical
      diagnosis of HD was confirmed by expanded CAG repeats (> 40). Coping strategies
      and depression levels were assessed before the results of DNA testing were
      imparted. The assessments were repeated two weeks and three months after the
      results were explained to the patients and their relatives and were compared to
      the baseline assessments. This group of HD patients was compared with 10 patients
      who had similar symptoms but the diagnosis of HD was excluded by normal CAG
      repeats (< 30). Although some patients with HD expressed a subjective reaction to
      the positive result (four were "surprised", one was "frustrated", and one
      "devastated"), there were no differences in any psychological scores including
      Beck Depression Inventory, functional capacity, symptom interference,
      independence scale, and other measures of mood and behaviour two weeks and three
      months later. Similarly, no change was noted in any of these measures in the non
      HD group. These results suggest that mood and coping strategies are unaffected by
      DNA confirmation of diagnosis in symptomatic patients with HD.

PMID- 7562961
TI  - Utilities for high throughput use of the single strand conformational
      polymorphism method: screening of 791 patients with familial
      hypercholesterolaemia for mutations in exon 3 of the low density lipoprotein
      receptor gene.
AB  - We have modified several aspects of the single strand conformational polymorphism
      (SSCP) method to increase the speed with which the technique can be used for
      mutation detection. The methods attain high resolution of small mobility
      differences using long (30 cm) gels and use a modified polymerase reaction to
      maximise detection sensitivity using a minimised quantity of 32P. By using custom
      cut "sharktooth" combs (4.5 mm between teeth) as the slot formers, commercially
      available multichannel pipettes (9 mm tip to tip) can be used to load eight or 12
      samples at a time from standard microtitre plates. PCR products that have been
      prepared and radiolabelled using simplified protocols are loaded on to the gel,
      and after a precalculated time of electrophoresis another set of samples can be
      loaded, either with combs moved across 2.25 mm or onto the same gel tracks. The
      run conditions are calculated so that there is no overlap between the bands
      produced by the two loadings, thus doubling the amount of information that can be
      gained from one gel. A computer program has been developed to solve equations to
      determine suitable timings for repetitive loadings. Finally, a modification of
      the gel pouring system is described so that two gels can be poured between three
      standard glass plates, with both gels run simultaneously. Of the order of 1000
      PCR reactions can be prepared and analysed in 24 man hours using five 40 cm x 30
      cm gel tanks. The application of these techniques is described to detect SSCPs in
      exon 3 of the low density lipoprotein receptor (LDLR) gene in 791 patients with
      familial hypercholesterolaemia (FH). Eight different SSCP patterns were seen, one
      of which was caused by the previously described E80K mutation, which was present
      in 11 patients (1.4%). In total, 32 patients (4%) were identified with exon 3
      mutations.

PMID- 7562960
TI  - FISH analysis on spontaneously arising micronuclei in the ICF syndrome.
AB  - The ICF syndrome is a rare disorder where patients show undercondensation of the
      heterochromatic blocks of chromosomes 1, 9, and 16 along with variable
      immunodeficiency. The undercondensation of the heterochromatic block appears to
      be restricted to a portion of PHA stimulated T cells. Patients with this syndrome
      also show an increase in micronuclei formation. We have used dual colour FISH to
      investigate the chromosomal content of these micronuclei in PHA stimulated
      peripheral blood cultures, an EBV transformed B cell line, and also micronuclei
      observed in vivo from peripheral blood smears. Chromosome 1 appears to be present
      in a higher proportion of micronuclei compared to chromosomes 9 and 16 in both a
      PHA stimulated culture and an EBV transformed cell line. An 18 centromeric probe,
      not associated with the ICF syndrome, showed no signal in any of the micronuclei
      observed. The implications from these observations are that the heterochromatic
      instability in the ICF syndrome is manifested not only in T but also in B cells
      and that it is present in vivo.

PMID- 7562963
TI  - Ascertainment of myotonic dystrophy through cataract by selective screening.
AB  - Myotonic dystrophy (DM) almost always results from the expansion of an unstable
      (CTG)n repeat. The mutation can be detected directly. Affected patients with
      cataracts may have minimal additional signs of the disorder, but all are at risk
      of life threatening complications. We have studied the efficacy of detecting new
      families with myotonic dystrophy by selectively screening cataract patients.
      Selection criteria were: age under 60 with no obvious precipitating factor
      (except non-insulin dependent diabetes mellitus (NIDDM)); patients of any age
      with other signs suggestive of myotonic dystrophy detected by the
      ophthalmologist. Ninety-six patients were tested prospectively; 17 others under
      55 were screened retrospectively. All patients were counselled by a clinical
      geneticist before testing. The patients' DNA was analysed using the DNA
      probe/restriction enzyme combinations GB2.6/EcoRI, KB1.4/BglI and polymerase
      chain reaction (PCR). Six patients have been found to have a mutation, three
      (3.1%) in the prospective group and three (17.6%) in the retrospective group.
      Three of these patients had minimal myotonic dystrophy and three had classical
      DM.

PMID- 7562964
TI  - The epidemiology of Huntington's disease in Northern Ireland.
AB  - A survey of Huntington's disease (HD) in Northern Ireland, with a population of
      1.5 million, has shown a 1991 prevalence rate of 6.4/100,000. Virtually complete
      ascertainment was achieved, enabling prevalence rate estimates and age statistics
      to be calculated over the last 20 years. The prevalence rate is similar to the
      high prevalence rates of HD found in most European populations, suggesting the
      presence of either one extremely ancient or a number of separate mutational
      origins, resulting in a uniform European HD prevalence. The ages at diagnosis and
      duration of the disease are similar to previous studies, suggesting a consistent
      effect of the HD gene in all families. Estimates of heterozygote frequency (HF),
      direct and indirect mutation rate, fertility, and genetic fitness (W) were made.
      Reliable HF estimates gave values between 10 and 11 x 10(-5). The direct and
      indirect mutation rates were 0.32 x 10(-6) and 1.05 x 10(-6) respectively. W was
      increased in the affected HD population but decreased in the at risk population.
      Fertility in HD is not reduced, but it appears that at risk patients have
      actively limited their family size. Factors responsible include, among others,
      the fear of developing HD and genetic counselling of families. This is the first
      published epidemiological survey to include ascertainment data in a population
      both before and after isolation of the HD gene, and with the diagnosis in
      virtually all patients confirmed by DNA mutation testing.

PMID- 7562965
TI  - Chromosome 13q deletion with Waardenburg syndrome: further evidence for a gene
      involved in neural crest function on 13q.
AB  - Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by
      pigmentary abnormalities and sensorineural deafness. It is subcategorised into
      type 1 (WS1) and type 2 (WS2) on the basis of the presence (WS1) or absence (WS2)
      of dystopia canthorum. WS1 is always caused by mutations in the PAX3 gene,
      whereas WS2 is caused by mutations in the microphthalmia (MITF) gene in some but
      not all families. An association of WS symptoms with Hirschsprung disease (HSCR)
      has been reported in many families. We report here a patient with characteristics
      of WS2 and a de novo interstitial deletion of chromosome 13q. We also describe a
      family with two sibs who have both WS2 and HSCR. In this family, all possible
      genes for WS and HSCR, but not chromosome 13q, could be excluded. As an
      association between chromosome 13q and HSCR/WS has been reported previously,
      these data suggest that there is a gene on chromosome 13q that is responsible for
      WS or HSCR or both.

PMID- 7562968
TI  - Confirmation of genetic heterogeneity in familial psoriasis.
AB  - Psoriasis affects approximately 2% of the European population and is often
      familial. Linkage of a subset of psoriasis families to loci on chromosome 17q has
      recently been reported. We have studied members of a large multiply affected
      family from the north east of England and analysed genotypes for markers from
      17q, including the polymorphic microsatellite markers AFM210xa5, AFM163yg1,
      AFM044xg3, AFMa353yg1, and AFM217yd19. Two point and multipoint analysis clearly
      show exclusion of linkage between the telomeric region of 17q and psoriasis in
      this family. This confirms the genetic heterogeneity of psoriasis and the
      existence of at least one other major psoriasis locus.

PMID- 7562966
TI  - The impact of newborn screening on cystic fibrosis testing in Victoria,
      Australia.
AB  - Newborn screening for cystic fibrosis (CF) by examining the levels of
      immunoreactive trypsinogen was introduced in Victoria in 1989. This was modified
      by the addition of testing for the common CF gene mutation, delta F508, in 1990.
      Problems with the first newborn screening protocol were overcome with the
      addition of the DNA test as there was no need to contact the majority of
      families, there was a reduced number of sweat tests, and less anxiety was
      experienced by parents. The mode of diagnosis changed from failure to thrive,
      steatorrhoea, rectal prolapse, and family history to diagnosis through newborn
      screening. Newborn screening dramatically reduced the time of diagnosis of CF to
      approximately six weeks or less in the majority of cases. Since the introduction
      of newborn screening, the uptake of prenatal diagnosis in CF families has
      increased two and a quarter fold.

PMID- 7562967
TI  - Population differences in the frequency of the factor V Leiden variant among
      people with clinically symptomatic protein C deficiency.
AB  - The factor V Leiden variant, responsible for the phenomenon of activated protein
      C resistance, was found to be less frequent among British (0.06) and
      Swedish/Danish (0.15) protein C deficiency patients than previously reported in a
      Dutch study (0.19). In the Swedish population, a significantly increased
      frequency of the factor V Leiden allele was apparent in protein C deficiency
      patients as compared to healthy controls. However, this was not found in the
      British population. Coinheritance of the factor V Leiden variant is therefore
      unlikely to be the sole determinant of whether a person with protein C deficiency
      will come to clinical attention. Nevertheless, when patient data were analysed by
      type of protein C deficiency, it was noted that the frequency of the factor V
      Leiden variant was 2.8-fold higher in type II patients compared to type I
      patients. A possible explanation of this disparity is discussed.

PMID- 7562969
TI  - Mutations in L1-CAM in two families with X linked complicated spastic paraplegia,
      MASA syndrome, and HSAS.
AB  - The suggestion that the three X linked syndromes X linked spastic paraplegia (MIM
      312900), MASA syndrome (MIM 303350), and X linked hydrocephalus owing to stenosis
      of the aqueduct of Sylvius (MIM 307000) are variable clinical manifestations of
      mutations at the same locus at Xq28 was confirmed by the finding of mutations in
      the L1-CAM gene in the three syndromes. Recently, two families in which different
      subjects showed a clearly different phenotype within the same family of the three
      X linked syndromes were described. A reverse transcription PCR assay was
      developed for the analysis of the L1-CAM cDNA in two of the members of these
      families. RNA isolated from EBV transformed cell lines and a colon carcinoma
      derived cell line was used as a starting material. The L1-CAM cDNA of two male
      patients from each family was sequenced. We report two new mutations in the L1
      CAM gene in these two families showing that the three different phenotypes
      observed in different generations within the same family are variable phenotypic
      expressions of the same mutation.

PMID- 7562970
TI  - Identification of constitutively activating mutation of the luteinising hormone
      receptor in a family with male limited gonadotrophin independent precocious
      puberty (testotoxicosis).
AB  - A family of male limited gonadotrophin independent precocious puberty was
      examined for activating mutation of the LH receptor. A transition of A to G in
      nucleotide 1733 of the human LH receptor gene was identified in all affected
      males and in an unaffected carrier female. The mutation was shown by identifying
      a new restriction site created by the mutation. This mutation appears to be a
      common feature of the disorder, as it has been reported previously in unrelated
      families. Therefore, the presence of this new restriction site can serve as a
      diagnostic tool in males at risk before the onset of symptoms, as well as
      identifying carrier females.

PMID- 7562971
TI  - Right upper limb bud triplication and polythelia, left sided hemihypertrophy and
      congenital hip dislocation, facial dysmorphism, congenital heart disease, and
      scoliosis: disorganisation-like spectrum or patterning gene defect?
AB  - A Somali female baby with right upper limb triplication, polythelia, left sided
      hemihypertrophy, congenital hip dislocation, facial dysmorphism, congenital heart
      disease, and scoliosis is described. It seems that the above described pattern of
      anomalies has not been reported before. The possible developmental genetic
      mechanism responsible for this phenotype is briefly discussed.

PMID- 7562972
TI  - A fetus with an X;1 balanced reciprocal translocation and eye disease.
AB  - A 19 week female fetus is described with a de novo X;1 reciprocal balanced
      translocation, with the breakpoint on the X chromosome at Xp11.4, and eye
      pathology consistent with the early stages of Norrie disease. The fetus seems to
      be an example of a female manifesting an X linked recessive disease, and it was
      shown that the normal X chromosome was completely inactivated in all cells
      examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ
      hybridisation studies showed that the Norrie disease gene had not obviously been
      disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of
      the coding region of the gene. Several eye disease genes map to the same region
      of the X chromosome, but are excluded on grounds of pathology. One possibility is
      that this fetus has a Norrie-like eye disease caused by the mutation of another
      gene located at Xp11.4. If this is so, there are implications for prenatal
      diagnosis.

PMID- 7562974
TI  - Molecular analysis of three patients with interstitial deletions of chromosome
      band 14q31.
AB  - Two patients and one three generation family with interstitial deletions of
      distal chromosome band 14q31 are described. The deletions were initially
      identified by chromosome analysis; we have used highly informative simple
      sequence repeat polymorphisms to define the deletions at the molecular level.
      This analysis also establishes the parental origin of the deleted chromosome. One
      of the patients was initially described as having a terminal deletion of
      chromosome 14 from 14q31 to 14qter; we show here that this child has instead an
      interstitial deletion of band 14q31. The smallest deletion involves a single
      anonymous DNA marker and is associated with an almost normal phenotype. The two
      patients with larger deletions have phenotypes similar to those seen in
      previously described cases of interstitial deletions of chromosome 14, including
      minor dysmorphic features and developmental delay. Delineation of these deletions
      allows the ordering of markers within the 14q31 region, in which the gene for the
      degenerative neurological disorder Machado-Joseph disease is localised.

PMID- 7562973
TI  - Cerebellar atrophy in a patient with velocardiofacial syndrome.
AB  - Velocardiofacial syndrome and DiGeorge syndrome have not previously been
      associated with central nervous system degeneration. We report a 34 year old man
      who presented for neurological evaluation with cerebellar atrophy of unknown
      aetiology. On historical review, he had neonatal hypocalcaemia, an atrial septal
      defect, and a corrected cleft palate. His physical examination showed the
      characteristic facies of velocardiofacial syndrome as well as dysmetria and
      dysdiadocho-kinesia consistent with cerebellar degeneration. Molecular
      cytogenetic studies showed a deletion of 22q11.2. This man is the first reported
      patient with the association of a neurodegenerative disorder and 22q11.2 deletion
      syndrome.

PMID- 7562975
TI  - Rapid detection of rare variants and common polymorphisms in the APC gene by PCR
      SSCP for presymptomatic diagnosis and showing allele loss.
AB  - During the course of screening the 5' half of exon 15 of the APC gene for
      germline and somatic mutations in two groups of patients, those with the
      inherited cancer prone syndrome adenomatous polyposis coli (APC) or with sporadic
      colorectal cancer, we have identified a number of intragenic changes that are not
      associated with the disease phenotype. Four of these changes are rare variants,
      each confined to one or two families and not detected in 50 additional unrelated
      people. Two common polymorphisms, at codon 1493 (exon 15I) and codon 1678 (exon
      15J), were extensively investigated and found to be in almost complete linkage
      disequilibrium not only with each other but with a previously described
      polymorphism at codon 1960 (exon 15N). The rapid and sensitive single strand
      conformation assay used provides an efficient method for presymptomatic diagnosis
      using intragenic variants and was additionally used to show allele loss at the
      APC locus in sporadic colorectal carcinomas.

PMID- 7562976
TI  - Chromosomal localisation of a Y specific growth gene(s).
AB  - Although a Y specific growth gene(s) has been postulated in the Yq11 region, the
      precise location has not been determined. To localise the growth gene(s), we
      correlated genotype with stature in 13 Japanese and four European non-mosaic
      adult male patients with a partial Yq deletion. Fourteen patients preserving the
      region between DYS11 and DYS246 did not have short stature (11 Japanese, 165-180
      cm; three Europeans, 165-173 cm) whereas the remaining three patients with the
      region deleted had short stature (two Japanese, both 159 cm; one European, 157
      cm). The results suggest that the region defined by DYS11 at interval 5C and by
      DYS246 at interval 5D may be the critical region for the Y specific growth
      gene(s).

PMID- 7562977
TI  - High incidence of delta I507 mutation of the CFTR gene in a limited area of the
      north west of France.

PMID- 7562978
TI  - Allele distribution of a highly polymorphic repeat on chromosome 12 in patients
      with symptoms of chorea and ataxia.

PMID- 7562980
TI  - A new method of comparative bone strength measurement.
AB  - Most investigations of the material properties of bone have been concerned with
      the measurement of absolute values for various mechanical parameters. It can be
      necessary, however, to produce test samples with similar mechanical properties in
      order to assess the effect on these properties of particular treatments. Absolute
      values for these properties may not be as important as any changes observed. We
      describe here a new method whereby many bone test samples with very similar
      mechanical properties can be produced. If the femoral shaft at the diaphysis is
      cut in transverse section, it is possible to produce many similar shaped rings of
      bone. We compared the material properties of 48 ring samples with 65 beam
      specimens. Both were tested in three-point bending. Global estimates of
      coefficient of variation (CV) for each parameter were used to assess similarity
      within each group. All the rings had very similar ash weights (1.98%),
      thicknesses (1.97%), and diameters (< 0.01%). Values of load/deflection of the
      rings were more similar than the values of Young's modulus (E) for the beams
      (7.06 versus 9.9%), and the maximum loads sustainable by the rings were more
      similar than the bending strengths of the beams (5.7 versus 13.6%). The energy
      absorbed by the ring samples were more consistent than the beams (14.31 versus
      34.41%). We suggest that there is improved similarity in mechanical
      characteristics within groups of samples produced in this manner than with more
      conventional sample configurations.

PMID- 7562979
TI  - Detection of Y mosaicism in patients with Turner's syndrome.

PMID- 7562981
TI  - Performance of angiographic catheters.
AB  - Simple methods of quantifying selected physical characteristics of angiographic
      catheters, which are likely to influence their in vivo performance, have been
      developed. The torsional stiffness ('torque') of catheters was measured, and tip
      control ('manoeuvrability') in an angiographic phantom was studied. Both braided
      and unbraided catheters were investigated all having the 'headhunter' tip shape.
      Significant differences between measurements made at 20 and 37 degrees C were
      found. Torsional stiffness was not a good predictor of performance in the
      angiographic phantom. Ethylene oxide re-sterilization has only a limited effect
      on the physical characteristics studied.

PMID- 7562983
TI  - Therapy for penicillin-resistant Streptococcus pneumoniae.

PMID- 7562982
TI  - An accurate 3-D model for magnetic stimulation of the brain cortex.
AB  - We present a 3-D model for the simulation of a realistic clinical situation
      during magnetic stimulation. The electromagnetic problem is solved by
      reconstructing the inhomogeneous head tissues from magnetic resonance images and
      associating relative values of conductivity to each tissue. Application of
      Maxwell's equations in the integral form leads to an equivalent 3-D electrical
      network, whose solution gives the current density distribution in the brain. The
      high spatial resolution and rigorous electromagnetic approach make this model an
      accurate and useful tool for stimulator design and for estimating the efficiency
      and safety of this clinical methodology.

PMID- 7562984
TI  - The phagocytosis of mycoplasmas.

PMID- 7562985
TI  - In-vivo induction of apoptosis in murine lymphocytes by bacterial
      lipopolysaccharides.
AB  - The effect of bacterial lipopolysaccharide (LPS) on the lymphoid organs in
      C3H/HeN and C3H/HeJ mice was investigated. In C3H/HeN mice, LPS induced
      apoptosis, characterised by morphological nuclear condensation and DNA
      fragmentation resulting in thymic atrophy. Similar but less severe changes were
      also observed in the spleen and lymph nodes. In C3H/HeJ mice, only a slight
      depletion of lymphocyte numbers was observed in the lymphoid organs. The plasma
      endotoxin levels were dependent on the LPS dose regardless of mouse strain. On
      the other hand, the plasma TNF-alpha levels were significantly elevated in
      C3H/HeN mice 1 h post-injection and the time course of plasma corticosterone
      concentration correlated well with the development of apoptosis. These findings
      suggest that TNF-alpha and corticosterone may play an important role in LPS
      induced apoptosis of lymphocytes.

PMID- 7562986
TI  - The influence of exo-enzyme S and proteases on endogenous Pseudomonas aeruginosa
      bacteraemia in mice.
AB  - The role of Pseudomonas aeruginosa exo-enzymes was evaluated in a murine model of
      endogenous bacteraemia in which the bacteria invaded the bloodstream after oral
      dosing. Although an elastase mutant PAO-E64 was as virulent as its parent strain
      PAO1, an exo-enzyme S-deficient mutant, DG1-ExS5 and alkaline protease mutants
      PAKS-16, PAKS-17, PAKS-19, were less virulent than their parent strains, DG1 and
      PAKS-1, respectively (p < 0.01). Thus exo-enzyme S and alkaline protease, but not
      elastase, appear to contribute to the pathogenicity of P. aeruginosa in this
      model.

PMID- 7562987
TI  - Further characterisation of a monoclonal antibody reactive with Escherichia coli
      O157:H7.
AB  - Monoclonal antibody (MAb) 4E8C12 has been previously reported to recognise low
      mol. wt proteins from enterohaemorrhagic Escherichia coli (EHEC) serotypes
      O157:H7 and O26:H11. Crude lipopolysaccharide (LPS) preparations from proteinase
      K-digested bacterial suspensions reacted in Western blots with MAb 4E8C12, as did
      highly purified LPS from O157:H7 strains. The material recognised by this
      antibody was, therefore, LPS. The LPS epitope was identified by a whole-cell
      ELISA in several EHEC, verotoxin producing E. coli (VTEC) and verotoxin-negative
      strains in addition to E. coli serotypes O157:H7 and O26:H11. Acriflavine and
      bile salts enhanced the production or availability of the epitope at the cell
      surface and in culture supernates. These data indicate that the presence of the
      epitope did not correlate with the virulence of these organisms.

PMID- 7562988
TI  - IgG subclass responses to Pseudomonas aeruginosa a- and b-type flagellins in
      patients with cystic fibrosis: a prospective study.
AB  - Sera from 20 cystic fibrosis patients, whose lungs were colonised by Pseudomonas
      aeruginosa, were examined in a 3-5-year prospective study for any relationship
      between IgG subclass antibody levels to P. aeruginosa a- and b-type flagellins
      and pulmonary function (FEV1 and radiological score). Patients were divided into
      two groups according to their pulmonary status: group 1 comprised 11 patients
      with poor pulmonary status; group 2 comprised nine patients with relatively good
      pulmonary status. High concentrations of IgG1, IgG2 and IgG3 antibodies to
      flagellins, particularly to the b-type, were found in most patients. IgG4
      reactivity was observed in only a few patients. Comparison of the two groups of
      patients showed that those with poor pulmonary status (group 1) had a
      significantly higher concentration (p < 0.05) of IgG3 for two of the three
      periods studied and of IgG2 for the last period studied. Moreover, IgG3 and IgG1
      reactivities to b-type flagellin and IgG3 to a-type flagellin were also increased
      significantly (p < 0.05) in group 1 patients between the first and the last
      period studied. These patients also showed a significant (p < 0.05) time
      dependent increase in IgG3 and IgG1 antibody concentrations. These data
      demonstrate that cystic fibrosis patients with poorer pulmonary status have
      higher IgG3 levels to flagellin than other cystic fibrosis patients. High
      concentrations of strong opsonic IgG3 and, to a lesser degree, of IgG1 antibodies
      may increase pulmonary inflammation and induce heightened pulmonary
      deterioration.

PMID- 7562989
TI  - Frequency analysis of proliferating and cytotoxic T cells in livers and
      peripheral blood of patients with chronic hepatitis B.
AB  - Frequencies of proliferating and cytotoxic lymphocytes from liver biopsy samples
      and peripheral blood of chronic hepatitis B (CHB) patients and control subjects
      were monitored by limiting dilution analysis. Precursor frequencies of
      proliferating T lymphocytes were not significantly different in the liver and
      peripheral blood compartments of patients and controls. Moreover, similar
      frequencies of natural killer cells and cytotoxic T lymphocytes were observed in
      the peripheral blood of patients and controls. A higher frequency of cytotoxic T
      cells (1 of 22) compared to NK cells (1 of 306) was observed in liver tissues of
      CHB patients. Dual colour flow cytometric analysis revealed the presence of both
      CD4+ HLA-DR+ and CD8+ HLA-DR+ T cells in the liver tissues. These results suggest
      that in livers of CHB patients not only activated CD8+ T cells but also activated
      CD4+ T cells may play a significant role in the pathogenesis of chronic hepatitis
      B.

PMID- 7562990
TI  - Purification and characterisation of a metallopeptidase of Candida albicans.
AB  - A novel aminopeptidase was purified by high performance liquid chromatography
      from a cytosoluble 100,000 g extract of Candida albicans on the basis of its
      ability to cleave L-arginine 7-amino-4-methylcoumarin. The purification factor
      was 36 and the yield was 20%. The native enzyme had a mol. wt of 52 kDa as
      demonstrated by SDS-PAGE in the presence or absence of reducing conditions and
      exhibited an iso-electric point of 4.3. The aminopeptidase showed optimum
      activity at pH 7.2, a Michaelis constant of c. 50 microM and a Vmax at 19 mM AMC
      released/min/mg of protein for L-Arg-AMC. This enzyme was shown to cleave at low
      affinity L-leucine-7-amino-4-methylcoumarin as demonstrated by the
      spectrofluorimetric method. The enzyme was strongly inhibited by specific metallo
      enzyme inhibitors-EDTA and o-phenanthroline. Furthermore, there is evidence that
      a similar or identical enzyme occurs in other C. albicans clinical isolates and
      other Candida spp.

PMID- 7562991
TI  - Virulence of Cryptococcus neoformans serotypes A, B, C and D for four mouse
      strains.
AB  - The relative virulence of Cryptococcus neoformans serotypes A, B, C and D in four
      mouse strains was assessed by measuring their migration from the foot-pad of the
      animals to the spleen, lungs and brain in 6-week-old DBA/2, BALB/c, A/J and a
      hybrid mouse strain by re-isolating yeasts from the internal organs. Comparable
      doses of each C. neoformans serotype were inoculated into the foot-pads of the
      mice. C. neoformans var neoformans strains A68, D52, A-(IN) and D-(IN) were more
      virulent than C. neoformans var gatti strains B112 and C18. However, the
      differences in the relative virulence of the var neoformans and the var gatti
      serotypes for the mouse strains were not significant (p > 0.05). Re-isolation of
      yeasts from mice showed that the BALB/c mice, in particular, and the DBA/2 mice
      were more susceptible to disseminated C. neoformans infection. The virulence of
      C. neoformans serotypes through foot-pad inoculation of mice was established.

PMID- 7562992
TI  - Resistance to extended-spectrum cephalosporins, caused by PER-1 beta-lactamase,
      in Salmonella typhimurium from Istanbul, Turkey.
AB  - Two Salmonella typhimurium isolates were studied, one as a representative from a
      series of neonatal meningitis cases treated at an Istanbul teaching hospital, the
      other from a gastro-enteritis case seen at a different Istanbul hospital. Both
      isolates were resistant to extended-spectrum cephalosporins, as well as
      penicillins, aminoglycosides and chloramphenicol. Cephalosporin resistance
      depended on production of PER-1 beta-lactamase, which is an extended-spectrum
      class A enzyme that is only distantly related to TEM and SHV enzymes, and which
      was previously known only from Pseudomonas aeruginosa isolates. The PER-1 gene
      was carried by an 81-MDa plasmid, which also determined resistance to
      aminoglycosides and chloramphenicol. Although it was not self-transmissible to
      Escherichia coli, this element did transfer if mobilised with plasmid pUZ8. The
      two S. typhimurium isolates gave indistinguishable DNA restriction patterns and,
      in addition to their 81-MDa plasmid, also contained 52- and 2.8-MDa plasmids, the
      last of these encoded TEM-1 enzyme. The two isolates were identical in serotype,
      antibiogram and plasmid-profile but nevertheless differed in phage type, and,
      therefore, represented distinct strains. The emergence of cefotaxime and
      ceftriaxone resistance in salmonellae is disturbing, since these agents are
      preferred therapy for neonatal meningitis caused by members of the genus.

PMID- 7562994
TI  - Proposed new bacterial taxa and proposed changes of bacterial names published
      during 1994 and considered to be of interest to medical or veterinary
      bacteriology.

PMID- 7562993
TI  - Mechanisms of resistance to beta-lactam antibiotics amongst Pseudomonas
      aeruginosa isolates collected in the UK in 1993.
AB  - Antimicrobial resistance among 1991 Pseudomonas aeruginosa isolates collected at
      24 UK hospitals during late 1993 was surveyed. Three-hundred and seventy-two of
      the isolates were resistant, or had reduced susceptibility, to some or all of
      azlocillin, carbenicillin, ceftazidime, imipenem and meropenem, and the
      mechanisms underlying their behaviour were examined. Only 13 isolates produced
      secondary beta-lactamases: six possessed PSE-1 or PSE-4 enzymes and seven had
      novel OXA enzyme types. Those with PSE types were highly resistant to azlocillin
      and carbenicillin whereas those with OXA enzymes were less resistant to these
      penicillins. Chromosomal beta-lactamase derepression was demonstrated in 54
      isolates, most of which were resistant to ceftazidime and azlocillin although
      susceptible to carbenicillin and carbapenems. beta-Lactamase-independent
      "intrinsic" resistance occurred in 277 isolates and is believed to reflect some
      combination of impermeability and efflux. Two forms were seen: the classical
      type, present in 195 isolates, gave carbenicillin resistance (MIC > 128 mg/L) and
      reduced susceptibility to ciprofloxacin and to all beta-lactam agents except
      imipenem; a novel variant, seen in 82 isolates, affected only azlocillin,
      ceftazidime and, to a small extent, meropenem. Resistance to imipenem was largely
      dissociated from that to other beta-lactam agents, and probably reflected loss of
      D2 porin, whereas resistance to meropenem was mostly associated with intrinsic
      resistance to penicillins and cephalosporins. Comparison of the present results
      with those of a similar study in 1982 revealed significant increases in the
      proportions of isolates with intrinsic resistance or stable derepression (p <
      0.01, chi 2 test).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7562995
TI  - Staphylococcal scalded skin syndrome.
AB  - Staphylococcal scalded skin syndrome (SSSS) is a recognised clinical entity that
      affects primarily the very young and, in rare cases, the very old or the
      immunocompromised. Koch's postulates have been fulfilled in that: (i)
      Staphylococcus aureus is isolated from every case; (ii) S. aureus can reproduce
      the syndrome in an experimental animal model; (iii) a specific extracellular
      toxin can reproduce the syndrome; and (iv) antibody to the toxin can protect
      experimental animals. Although exfoliative toxin (ET) is responsible for the skin
      loosening seen in SSSS, it does not account for all the symptoms of the disease.
      Purified ET does not cause erythema in either neonatal mice or man, and the
      lesions are not painful unless the loosened epidermis is removed. This suggests
      that other factors, e.g., delta-haemolysin, are involved in the pathogenesis of
      this condition. Although much has been learned about the pathogenesis of the
      syndrome, we are still largely ignorant of the factors which govern host
      resistance to SSSS (i.e., intoxication by ET-producing strains of S. aureus). It
      is fortunate from the patient's point of view that the aetiological agent can be
      destroyed readily by the use of appropriate antibiotic therapy.

PMID- 7562996
TI  - Antibody response to Staphylococcus aureus collagen binding protein in patients
      with S. aureus septicaemia and collagen binding properties of corresponding
      strains.
AB  - An ELISA was developed for the detection of IgG antibodies to Staphylococcus
      aureus collagen binding protein (CnBP) in 95 patients with S. aureus
      endocarditis, complicated septicaemia with bone and joint involvement or
      uncomplicated septicaemia and in 95 control patients. Sixty percent of S. aureus
      infected patients showed a positive peak anti-CnBP antibody level or a
      significant rise in titre, or both, during infection, but patients with S. aureus
      endocarditis or complicated septicaemia could not be differentiated from those
      with uncomplicated S. aureus septicaemia. The collagen binding capacity of S.
      aureus strains from 82 of the 95 patients was investigated in a particle
      agglutination assay and a 125I-labelled assay. All strains bound collagen in the
      particle agglutination assay as did 68% in the 125I-labelled assay, but there was
      no correlation between collagen binding of the patient strain and endocarditis,
      joint or skeletal involvement. An anti-CnBP antibody response was seen in 16
      patients infected with a S. aureus strain negative for collagen binding in vitro,
      indicating in-vivo expression of CnBP.

PMID- 7562997
TI  - Antibodies to meningococcal class 1 outer-membrane protein and its variable
      regions in patients with systemic meningococcal disease.
AB  - Antibodies to the meningococcal serosubtype-specific P1.7,16 protein and its
      variable regions (VR) were analysed in 28 convalescent sera drawn 8-36 months
      after systemic meningococcal disease by immunoblotting and enzyme immunoassay
      (EIA) methods. EIA antigens were the meningococcal P1.7,16 protein, produced in
      Bacillus subtilis, and peptides covering its VR1 (P1.7 region) and VR2 (P1.16
      region) inserted into a bacterial penicillinase protein. In the immunoblotting
      method, three meningococcal reference strains were used; they expressed either
      the P1.7,16 protein, or only its VR1 or VR2 epitopes in their class 1 proteins.
      Both methods showed a strong IgG response in four sera to P1.7,16 and VR2, but
      not to VR1; 18 sera had no or weak anti-class 1 protein activity. The six
      remaining sera were positive only on blots. The VR2-specific sera had 30-fold
      higher bactericidal activity than those with negligible P1.7,16 responses.
      Previous vaccination of the patients with a B:15:P1.7,16 meningococcal vaccine
      was associated with a strong anti-P1.7,16 and anti-VR2 booster response that
      declined with time. The subtype-specific antibody activity in some sera indicated
      colonisation after disease by meningococci with class 1 proteins different from
      the strain that had caused disease.

PMID- 7562998
TI  - Outer-membrane protein- and rough lipopolysaccharide-specific monoclonal
      antibodies protect mice against Brucella ovis.
AB  - Brucella ovis, a naturally virulent rough Brucella species, is the aetiological
      agent of ram epididymitis. The identification of protective antigens is necessary
      to obtain a safe, specific subcellular vaccine. Monoclonal antibodies (MAbs)
      directed at both brucella outer-membrane proteins (OMPs) and rough
      lipopolysaccharide (R-LPS) in a mouse protection test were used to identify
      potential targets for humoral immunity. Mixtures of MAbs directed at the 16.5-,
      25-27-, 31-34- and 36-38-kDa OMPs conferred significant protection 7 days after
      challenge with reference strain B. ovis 63/290 compared with controls receiving
      either saline or an anti-brucella O-polysaccharide MAb. Furthermore, an anti-R
      LPS MAb tested alone conferred protection at a level comparable with that
      obtained with the mixture of anti-OMP MAbs. The combination of protective OMP
      MAbs with the anti-R-LPS MAb was also strongly protective. One combination of OMP
      MAbs, which bound intensely to B. ovis in vitro, was ineffective. These results
      indicate that B. ovis OMPs and R-LPS are targets for protective antibodies and
      that they can be regarded as candidates for ram epididymitis subcellular
      vaccines.

PMID- 7563000
TI  - Cytotoxin detection in Campylobacter jejuni strains of human and animal origin
      with three tissue culture assay systems.
AB  - Cytotoxin (CTX) production in 34 human and 22 animal strains of Campylobacter
      jejuni isolated in Japan and other countries was studied by three assay systems
      described previously. Furthermore, cholera-like enterotoxin production by these
      strains was tested by reversed passive latex agglutination (RPLA). CTX titres in
      the fetal calf serum (FCS) and newborn calf serum (NCS) assays were relatively
      lower, with a maximum of 4 and 8, respectively, than the maximum of 128 for the
      serum-free culture (SFC) assay. CTX detection rates were 62, 85 and 100% in human
      isolates and 64, 77 and 100% in animal isolates for the FCS, NCS and SFC assay
      systems, respectively. There was no significant difference in the detection rate
      of CTX between human and animal isolates, or between human isolates from Japan
      and other countries. With the three assay systems, the strains were divided into
      four groups from the pattern of CTX detection; 54% of strains gave positive
      results in all three assay systems, and 9% of them were positive in the SFC assay
      only. Morphological changes on CHO cells showed distended instead of rounded
      cells with eight of 21 strains negative in the FCS assay. Cholera-like
      enterotoxin was not detected in the culture filtrate of any of the strains when
      tested by RPLA. These results indicate that cytotoxin production by C. jejuni is
      complex as compared with that of other enteric pathogens.

PMID- 7562999
TI  - Pheno-genotyping of verotoxin 2 (VT2)-producing Escherichia coli causing
      haemorrhagic colitis and haemolytic uraemic syndrome by direct analysis of
      patients' stools.
AB  - The subtype of verotoxin 2 (VT2) found in 22 VT2-positive stool samples from
      severely diseased Italian and German children with haemorrhagic colitis or
      haemolytic uraemic syndrome, or both, and that produced by the corresponding VT
      producing Escherichia coli (VTEC) strains isolated from the stools were studied
      by cytotoxicity seroneutralisation assays and by polymerase chain reaction (PCR)
      amplification of the VT2 B-subunit gene, followed by restriction fragment length
      polymorphism (RFLP) analysis. The free faecal toxin was serotyped as the
      classical VT2 in 21 stool samples, and as the VT2 variant VT2c in one. For all
      but one of the VTEC isolates, the toxin phenotype was consistent with the type of
      VT produced in vivo and found in the corresponding stool samples. Genotyping was
      in agreement with phenotyping for those strains harbouring a single type of VT2
      gene. Three O157:H7 isolates carrying both VT2 and VT2c genes had the VT2
      phenotype, instead of the expected VT2c phenotype. Direct PCR analysis of stools
      detected VT genes in only 11 of 20 VT-positive stool samples suggesting that the
      Vero cell cytotoxicity assay is more sensitive in diagnosing VTEC infection.
      Immunological and genetic subtyping of VT2 performed directly on stool samples
      from patients with haemolytic uraemic syndrome could be a useful complementary
      approach to understanding the role of the different types of VT in this syndrome.

PMID- 7563001
TI  - An alpha 5 beta 1-like integrin receptor mediates the binding of less pathogenic
      Candida species to fibronectin.
AB  - The present study was undertaken to investigate whether less pathogenic Candida
      species (C. tropicalis, C. stellatoidea, C. krusei and C. glabrata) express a
      fibronectin receptor (FNr) antigenically related to alpha 5 beta 1 integrin,
      which mediates their binding to fibronectin (FN). By flow cytometric analysis, a
      monoclonal antibody (MAb) directed against human alpha 5 integrin subunit (clone
      SAM-1) and two different antisera to FNr positively stained C. tropicalis, C.
      stellatoidea and C. glabrata, with the greatest expression observed for C.
      tropicalis. No or only marginal immunoreactivity was found on C. krusei. C.
      tropicalis, C. stellatoidea, C. glabrata, but not C. krusei yeasts specifically
      adhered to FN; higher levels of adhesion were found for C. tropicalis and C.
      stellatoidea with respect to C. glabrata. Less pathogenic Candida spp. bound to
      the Arg-Gly-Asp (RGD) containing 120-kDa fragment of FN and adhesion to intact FN
      was markedly inhibited by Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), but not by Gly-Arg
      Gly-Glu-Ser-Pro (GRGESP) peptides. In addition, anti-alpha 5 SAM-1 MAb and both
      anti-FNr antisera strongly blocked binding of less pathogenic Candida spp. to FN.
      Overall, these results indicate that less pathogenic Candida spp., including C.
      tropicalis, C. stellatoidea and C. glabrata, express a receptor antigenically
      related to alpha 5 beta 1 integrin which mediates their adhesion to FN.

PMID- 7563004
TI  - Susceptibility of Streptococcus pyogenes to azithromycin, clarithromycin,
      erythromycin and roxithromycin in vitro.
AB  - The susceptibility of 180 clinical isolates of Streptococcus pyrogenes from six
      regions of The Netherlands to the macrolide antibiotics azithromycin,
      clarithromycin, erythromycin and roxithromycin was analysed. The results of a
      microbroth MIC method, the E-test method and a disk diffusion assay were
      compared, and the MBC determined. In addition, the susceptibility to erythromycin
      of 436 clinical isolates of S. pyogenes from the Leiden region was determined.
      The microbroth MIC90s of azithromycin, clarithromycin, erythromycin and
      roxithromycin for group A streptococci were < or = 0.5 mg/L. Erythromycin had the
      lowest MIC90 (0.09 mg/L). The MIC data obtained with the E-test method suggested
      that clarithromycin and erythromycin had slightly higher anti-streptococcal
      activity than azithromycin and roxithromycin in vitro. MICs obtained with the E
      test were lower than those found with the microbroth method. Only minor
      discrepancies were observed among the three methods. The MBC50 for both
      clarithromycin and erythromycin was 0.75 mg/L and 5.0 mg/L for azithromycin and
      roxithromycin. None of the 180 strains and two of the collection of 436 strains
      (0.5%) were resistant to erythromycin and the other macrolides tested; MICs
      ranged from 1 to 16 mg/L. The erythromycin-resistant strains showed an inducible
      type of macrolide-lincosamide-streptogramin B (MLS) resistance.

PMID- 7563003
TI  - Penicillin-resistant Streptococcus pneumoniae in Germany: genetic relationship to
      clones from other European countries.
AB  - Penicillin-resistant Streptococcus pneumoniae strains isolated in different parts
      of Germany between 1982 and 1992 were compared with penicillin-resistant
      isolates, mainly of serogroups 6, 9, 14, 19 and 23, from other European
      countries. The main clones were recognised by their serotypes, antibiotic
      resistance patterns and penicillin-binding protein properties, and this typing
      was confirmed by multi-locus enzyme electrophoresis for a sample of 43 selected
      isolates. Eleven of the 14 resistant German isolates could be assigned to five
      genotypes isolated also in other countries. These included representatives of two
      distinct serotype 23F lineages predominant in Spain and France; a cluster of
      three serotype 6B isolates identical to clones in Spain, France, Finland and
      Hungary; and a serotype 9V clone of a type prevalent in Spain and now also in
      France. Serotype 19A clones of the type found in Hungary were not collected in
      Germany. The data suggest that two 23F lineages, represented by seven isolates
      from different locations, have become disseminated in Germany. Several resistant
      types found in the former West Germany resembled those found elsewhere in Western
      Europe whereas those from East Germany were distinct or, in one case, resembled a
      clone from Hungary. These data may reflect pre-unification travel patterns.

PMID- 7563002
TI  - Efficacy of sustained release ciprofloxacin microspheres against device
      associated Pseudomonas aeruginosa biofilm infection in a rabbit peritoneal model.
AB  - The relative effectiveness of a poly(L-lactic acid) ciprofloxacin hydrochloride
      (CIP) microsphere formulation (250-425 microns) against peritoneal implanted
      biofilm of Pseudomonas aeruginosa was investigated in a rabbit model.
      Correlations between in-vivo CIP pharmacokinetics in peritoneal dialysate and
      serum after intraperitoneal administration, in-vivo cell counts and rabbit
      survival rate were obtained. Dialysate and serum concentrations after 12 h (C12h)
      were greater than those obtained with free drug whereas maximum serum
      concentrations (Cmax) were lower and the time to reach Cmax(tmax) was longer. A
      silastic implant device pre-colonised with P. aeruginosa for 2 days was implanted
      in the rabbit peritoneum, and dialysate with or without drug or microspheres was
      administered via a catheter. Rabbits receiving no antibiotic and those receiving
      free drug (10 mg in dialysate) died of peritonitis and septicaemia, whereas all
      rabbits given CIP microspheres recovered completely from infection. The viable
      count of P. aeruginosa was markedly reduced or eliminated from the catheter, the
      device and the peritoneal wall in CIP microsphere-treated rabbits but not in
      rabbits treated with free drug, as determined from histological and scanning
      electronmicroscopic evidence. These results demonstrate that sustained release of
      antibiotics at biofilm eradication concentrations (BEC) is required to treat
      biofilm infections associated with peritoneal implanted devices.

PMID- 7563005
TI  - Antihypertensive effects of captopril without adverse effects on glucose
      tolerance in hyperinsulinemic rhesus monkeys.
AB  - The rhesus monkey (Macaca mulatta), which has been found to develop spontaneous
      obesity, non-insulin dependent diabetes mellitus (NIDDM; Type 2), and
      hypertension, was used to evaluate the potential blood pressure-lowering effects
      of captopril as well as the specific effects, if any, on the prediabetic state.
      Intravenous and oral glucose tolerance testing was carried out with oral
      captopril dosing. Results showed that captopril significantly decreased both
      systolic and diastolic blood pressure in all monkeys and significantly decreased
      fasting plasma glucose levels. Based on these preliminary studies in monkeys, we
      conclude that captopril exerted antihypertensive effects without adverse effects
      on glucose metabolism.

PMID- 7563006
TI  - Feeding enrichment and body weight in captive chimpanzees.
AB  - Although positive behavioral consequences have been attributed to feeding
      enrichment, physiological changes may also occur. In this study, the body weight
      records of a large chimpanzee colony were reviewed to determine if body weight
      was affected by the implementation of a daily enrichment program, including food
      items offered three to four times per week. Comparing the mean body weight by age
      groups indicated that the weight of female chimpanzees was significantly greater
      after feeding enrichment but that male body weight did not differ.

PMID- 7563007
TI  - Normal serum biochemical and hematological values of the Sulawesi macaques.
AB  - Sulawesi macaque (SM) species are currently of interest to primatologists for
      genetic and behavioral studies world wide. However, there are no published
      reference hematological and serum biochemical profile values for several of the
      seven SM species. Twenty-five clinically healthy, outdoor housed, ketamine
      sedated Macaca tonkeana and Macaca maurus were serially sampled (two to four
      times) over a 16-month period (N = 68). Normal ranges were defined to include two
      standard deviations and 2.5-97.5 percentile. Significant differences in single
      sample data comparisons (P < 0.05) of species (serum Ca, MCHC), age (BUN,
      BUN/creatinine, alkaline phosphatase, phosphorus), gender (total protein, RBC,
      hemoglobin, HCT) and pregnancy (phosphorus and neutrophil count) groups were
      found. This normative data facilitates clinical evaluation of SM species and
      allows comparison to other macaque species.

PMID- 7563008
TI  - A baboon (Papio hamadryas) model of insulin-dependent diabetes.
AB  - Over a period of four years, streptozocin has been used to induce diabetes in 10
      baboons, all of whom are insulin dependent. We describe our experience with their
      husbandry, induction of diabetes, insulin therapy, metabolic control and growth
      rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal
      hepatic or renal toxicity. Using a once daily injection of mixed short and
      intermediate acting insulins at a dosage of 2-4 U/kg, it is possible to maintain
      a degree of metabolic control similar to that attained in patients.

PMID- 7563009
TI  - Presence of virion protein x (Vpx) of simian immunodeficiency virus SIVmac 251 in
      target cells in vivo.
AB  - Localization of virion-associated protein x (Vpx) of SIVmac 251 was studied in
      lymph nodes and liver of six SIVmac-infected monkeys. Vpx was found associated
      with the network of follicular dendritic cells and macrophages in lymph nodes
      and/or livers from five out of six animals by immunohistochemistry. Although the
      humoral response to Vpx occurs in only 50% of the animals, the presence of Vpx in
      target cell or antibodies to Vpx in all the monkeys studied, suggests that Vpx
      may be necessary for viral replication in vivo.

PMID- 7563011
TI  - Melanotic ependymoma in a Goeldi's marmoset (Callimico goeldii).
AB  - A spontaneous melanotic ependymoma was observed in the brain of an adult female
      Goeldi's marmoset (Callimico goeldii). The mass completely occupied the left
      lateral ventricle, rupturing the fornix and corpus callosum, and compressing the
      adjacent neuropil. Special histochemical techniques, including melanin bleach,
      periodic acid-Schiff, Perls iron and phosphotungstic acid hematoxylin,
      demonstrated the neoplasms to be an ependymoma with a rare melanotic
      differentiation.

PMID- 7563010
TI  - Immunocytochemistry of Kaposi's sarcoma-like tumor cells from pigtailed macaques
      with simian AIDS.
AB  - Some macaques infected with SRV-2 developed SAIDS and RF, a Kaposi's sarcoma (KS)
      like tumor. We investigated the immunophenotypic markers of this SAIDS-associated
      retroperitoneal fibromatosis (RF). RF tumor is characterized by proliferation of
      spindle cells accompanying inflammatory cell infiltrates, fibroblasts, and
      endothelial cells. RF spindle cells in tumor tissues revealed several
      immunobiologic characteristics similar to vascular smooth-muscle cells or
      myofibroblasts based on positive immunoreactivity of smooth-muscle alpha-actin
      and desmin. The majority of cultured RF spindle cells also expressed specific
      markers for vascular smooth muscle. These results suggest that the RF spindle
      cells are derived from vascular smooth-muscle cells. Furthermore, RF tissues and
      cells were persistently infected with SRV-2, which may play an important role in
      viral etiology of AIDS-associated neoplasm in this macaque model.

PMID- 7563012
TI  - Anti-human gonadotropin antibodies generated during in vitro fertilization (IVF)
      related cycles: effect on fertility of rhesus macaques.
AB  - Administration of human gonadotropins such as hFSH, hLH, and hCG to rhesus
      macaques can result in formation of anti-human gonadotropin antibodies. To
      determine whether the presence of these antibodies interferes with subsequent
      fertility, sixteen female rhesus macaques (Macaca mulatta) with known antibody
      levels were bred with male rhesus macaques. The presence of antibodies did not
      interfere with conception or maintenance of pregnancy. Furthermore, antibody
      titers did not increase during gestation or following the resolution of
      pregnancy.

PMID- 7563013
TI  - Calcium and inositol trisphosphate receptors.

PMID- 7563014
TI  - Sodium currents in toad cardiac pacemaker cells.
AB  - Cells in the pacemaker region of toad (Bufo marinus) sinus venosus had
      spontaneous rhythmic action potentials. The rate of firing of action potentials,
      the rate of diastolic depolarization and the maximum rate of rise of action
      potentials were reduced by TTX (10 nM to 1 microM). Currents were recorded with
      the whole cell, tight seal technique from cells enzymatically dissociated from
      this region. Cells studied were identified as pacemaker cells by their
      characteristic morphology, spontaneous rhythmic action potential activity that
      could be blocked by cobalt but not by TTX and lack of inward rectification. When
      calcium, potassium and nonselective cation currents (If) activated by
      hyperpolarization were blocked, depolarization was seen to generate transient and
      persistent inward currents. Both were sodium currents: they were abolished by
      tetrodotoxin (10 to 100 nM), their reversal potential was close to the sodium
      equilibrium potential and their amplitude and reversal potential were influenced
      as expected for sodium currents when extracellular sodium ions were replaced with
      choline ions. The transient sodium current was activated at potentials more
      positive than -40 mV while the persistent sodium current was obvious at more
      negative potentials. It was concluded that, in toad pacemaker cells, TTX
      sensitive sodium currents contributing both to the upstroke of action potentials
      and to diastolic depolarization may play an important role in setting heart rate.

PMID- 7563015
TI  - Cellular chloride depletion inhibits cAMP-activated electrogenic chloride fluxes
      in HT29-18-C1 cells.
AB  - Cyclic AMP-activated chloride fluxes have been analyzed in HT29-18-C1 cells (a
      clonal cell line derived from a human colon carcinoma) using measurements of cell
      volume (electronic cell sizing), cell chloride content (chloride titrator) and
      intracellular chloride activity (6-methoxy-N-(3-sulfopropyl)quinolinium; SPQ).
      HT29-18-C1 was shown to mediate polarized chloride transport. In unstimulated
      cells, the apical membrane was impermeable to chloride and net chloride flux was
      mediated by basolateral furosemide-sensitive transport. Forskolin (10 microM)
      increased furosemide-insensitive chloride permeability of the apical membrane,
      and decreased steady-state intracellular chloride concentration approximately 9%.
      Cellular chloride depletion (substitution of medium chloride by nitrate or
      gluconate), caused greater than fourfold reduction in cellular chloride
      concentration. When chloride-depleted cells were returned to normal medium, cells
      regained chloride and osmolytes via bumetanide-sensitive transport, but forskolin
      did not stimulate bumetanide-insensitive chloride uptake. The inhibition of cAMP
      activated chloride reuptake was not explained by limiting cation conductance,
      cell shrinkage, choice of substitute anion, or decreased generation of cAMP in
      chloride-depleted cells. When cells with normal chloride content were depolarized
      (135 mM medium potassium + 10 microM valinomycin), cAMP activated electrogenic
      chloride uptake permselective for Cl- approximately Br- > NO3- > I-. The
      electrogenic transport pathway was inhibited in chloride-depleted cells. Results
      suggest that chloride depletion limits activation of electrogenic chloride flux.

PMID- 7563016
TI  - Characterization of the acetylcholine-sensitive muscarinic K+ channel in isolated
      feline atrial and ventricular myocytes.
AB  - M2-cholinergic receptor activation by acetylcholine (ACh) is known to cause a
      negative inotropic and chronotropic action in atrial tissues. This effect is
      still controversial in ventricular tissues. The ACh-sensitive muscarinic K+
      channel (IK(ACh)) activity was characterized in isolated feline atrial and
      ventricular myocytes using the patch-clamp technique. Bath application of ACh (1
      microM) caused shortening of action potential duration without prior stimulation
      with catecholamines in atrial and ventricular myocytes. Resting membrane
      potential was slightly hyperpolarized in both tissues. These effects of ACh were
      greater in atrium than in ventricle. ACh increased whole-cell membrane current in
      atrial and ventricular myocytes. The current-voltage (I-V) relationship of the
      ACh-induced current in ventricle exhibited inward-rectification whose slope
      conductance was smaller than that in atrium. In single channel recording from
      cell-attached patches, IK(ACh) activity was observed when ACh was induced in the
      pipette solution in both tissues. The channel exhibited a slope conductance of 47
      +/- 1 pS (mean +/- SD, n = 14) in atrium and 47 +/- 2 pS (n = 10) in ventricle
      (not different statistically; NS). The open times were distributed according to a
      single exponential function with mean open lifetime of 2.0 +/- 0.3 msec (n = 14)
      in atrium and 1.9 +/- 0.3 msec (n = 10) in ventricle (NS); these conductance and
      kinetic properties were similar between the two tissues. However, the
      relationship between the concentration of ACh and single channel activity showed
      a higher sensitivity to ACh in atrium (IC50 = 0.03 microM) than in ventricle
      (IC50 = 0.15 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563018
TI  - Sequential potassium binding at the extracellular side of the Na,K-pump.
AB  - Ion binding at the extracellular face of the Na,K-ATPase is electrogenic and can
      be monitored by the styryl dye RH 421 in membrane fragments containing a high
      density of the Na,K-pumps. The fluorescent probe is noncovalently bound to the
      membrane and responds to changes of the local electric field generated by binding
      or release of cations inside the protein. Due to the fact that K+ binding from
      the extracellular side is an electrogenic reaction, it is possible to detect the
      amount of ions bound to the pump as function of the aqueous concentration. The
      results are in contradiction to a second order reaction, i.e., a simultaneous
      binding of two K+ ions. A mathematical model is presented to discuss the nature
      of the two step binding process. On the basis of this model the data allow a
      quantitative distinction between binding of the first and the second K+ ion. The
      temperature dependence of ion binding has been investigated. At low temperatures
      the apparent dissociation constants differ significantly. In the temperature
      range above 20 degrees C the resulting apparent dissociation constants for both
      K+ ions merge and have values between 0.2 and 0.3 mM, which is consistent with
      previous experiments. The activation energy for the half saturating concentration
      of K+ is 22 kJ/mol. Additional analysis of the titration curve of K+ binding to
      the state P-E2 by the Hill equation yields a Hill coefficient, nHill, of 1.33,
      which is in agreement with previously published data.

PMID- 7563019
TI  - Effects of voltage clamping on epithelial cell composition in toad urinary
      bladder studied with x-ray microanalysis.
AB  - Toad urinary bladder epithelial cells were incubated in Na Ringer's with the
      serosal surface of the epithelium clamped at either +50 mV, 0 mV (short
      circuited) or -50 mV with respect to the mucosal surface. Following incubation,
      portions of tissue were coated with an external albumin standard and rapidly
      frozen. Cryosections were freeze-dried and cell composition determined by x-ray
      microanalysis. Cell water and ion contents were unaffected when tissues were
      short-circuited rather than clamped close to their open-circuit potential
      difference (+50 mV). Incubation with vasopressin at +50 mV, and under short
      circuit conditions, caused Na uptake without cell swelling or gain in Cl.
      Clamping at -50 mV resulted in uptake of water and ions, with considerable
      variation from cell to cell. These variations in cell composition were
      exacerbated by vasopressin. The greater the increase in water content, the
      greater the rise in cell Cl. However, there was no consistent pattern to the
      associated changes in cation contents. Most cells gained some Na. In some cells,
      this gain was accompanied by an increase in K. In others, the gain of Na was
      predominant and cell K content actually fell. At -50 mV with ouabain, many of the
      cells also gained water. As was found in our earlier study with ouabain under
      short circuit conditions (Bowler et al., 1991), there was considerable variation
      in the extent of the Na gain and K loss; some cells were largely depleted of K
      while in others the K content remained relatively normal. These results indicate
      differences between granular cells in the availabilities in the plasma membranes
      of ion pathways, either as a consequence of differences in the numbers of such
      pathways or in their control.

PMID- 7563017
TI  - Electrical currents generated by a partially purified Na/Ca exchanger from
      lobster muscle reconstituted into liposomes and adsorbed on black lipid
      membranes: activation by photolysis of Ca2+.
AB  - The Na/Ca exchanger from lobster muscle crossreacts specifically with antibodies
      raised against the dog heart Na/Ca exchanger. Immunoblots of the lobster muscle
      and mammalian heart exchangers, following SDS-PAGE, indicate that the
      invertebrate and mammalian exchangers have similar molecular weights: about 120
      kDa. The exchanger from lobster muscle was partially purified and functionally
      reconstituted into asolectin vesicles which were loaded with 160 mM NaCl. 45Ca
      uptake by these proteoliposomes was promoted by replacing 160 mM NaCl in the
      external medium with 160 mM KCl to produce an outwardly-directed Na+
      concentration gradient. When the proteoliposomes were adsorbed onto black lipid
      membranes (BLM), and DM-Nitrophen-Ca2+ ("caged Ca2+") was added to the KCl
      medium, photolytically-evoked Ca2+ concentration jumps elicited transient
      electric currents. These currents corresponded to positive charge exiting from
      the proteoliposomes, and were consistent with the Na/Ca exchanger-mediated exit
      of 3 Na+ in exchange for 1 entering Ca2+. The current was dependent upon the Ca2+
      concentration jump, the protein integrity, and the outwardly directed Na+
      gradient. KCl-loaded proteoliposomes did not produce any current. Low external
      Na+ concentrations augmented the current, whereas Na+ concentrations > 25 mM
      reduced the current. The dependence of the current on free Ca2+ was Michaelis
      Menten-like, with half-maximal activation (KM(Ca)) at < 10 microM Ca2+. Caged
      Sr2+ and Ba2+, but not Mg2+, also supported photolysis-evoked outward current, as
      did Ni2+, but not Mn2+. However, Mg2+ and Mn2+ augmented the Ca-dependent
      current, perhaps by facilitating the adsorption of proteoliposomes to the BLM.
      The Ca-dependent current was irreversibly blocked by La3+ (added as 200 microM
      DMN-La3+). The results indicate that the properties of the Na/Ca exchanger can be
      studied with these electro-physiological methods.

PMID- 7563020
TI  - Sodium channels in cultured neuroblastoma cells grown in high glucose or L
      fucose.
AB  - Patch clamp techniques were used to record whole cell and single channel Na+
      currents from NB41A3 neuroblastoma cells grown in culture. Cells were grown for
      two weeks in control medium or medium supplemented with 30 mM D-glucose of 30 mM
      L-fucose. Cells exposed to glucose or L-fucose had smaller whole cell Na+
      currents than cells grown in unsupplemented medium, consistent with earlier
      studies (Yorek, Stefani & Wachtel, 1994). Whole cell macroscopic currents showed
      no change in activation or inactivation kinetics. Single channel current
      properties and opening probability were also unchanged. The number of
      [3H]saxitoxin binding sites, and therefore the total number of Na+ channels, was
      not reduced in cells grown in glucose or L-fucose (Yorek et al., 1994).
      Therefore, we conclude that some of the channels must have been rendered
      nonfunctional by the conditioning media. The finding that single channel
      properties are not altered suggests that channels become nonfunctional in an all
      or-none manner.

PMID- 7563021
TI  - Cytoskeletal disruption in A6 kidney cells: impact on endo/exocytosis and NaCl
      transport regulation by antidiuretic hormone.
AB  - Antidiuretic hormone (ADH; 2.5 x 10(-8) M vasotocin) produces a stimulation of
      apical fluid phase endocytosis, protein secretion and NaCl reabsorption in
      Xenopus laevis A6 distal nephron cell epithelia pretreated with aldosterone (10(
      6) M). The increase of NaCl transport is mediated by a sequential opening of
      apical Cl and Na conductances. The aim of this study was to characterize the
      actin and tubulin cytoskeleton of A6 cells and to assess the impact of its
      disruption on baseline and ADH-induced apical vesicular membrane movements and
      ion transport to test for possible functional links. The microfilament (MF) and
      microtubule (MT) networks and their disruption were visualized by confocal laser
      microscopy. Conditions of depolimerization were selected, by cytochalasin D or
      cold and nocodazole, respectively. MF disruption produced an increase in baseline
      apical protein secretion (exocytic movements) (plus 18%) and a decrease of its
      induction by ADH (minus 35%). MF disruption also increased baseline horseradish
      peroxidase uptake (endocytic movements) (plus 21%), however, without affecting
      its ADH-induced increase. In the case of MT disruption, the ADH-induced
      stimulation of both protein secretion and fluid phase endocytosis was decreased
      by 70 and 44%, respectively. At the ion transport level, MF and MT disruption
      only insignificantly affected the ADH-induced Cl conductance, while they
      decreased the ADH-induced stimulation of Na transport (amiloride-sensitive short
      circuit current and conductance) by a factor of 2 to 4. In conclusion, both MT
      and MF disruption decrease ADH-induced apical protein secretion and Na
      conductance, while the ADH-induced apical Cl conductance is not significantly
      affected. Taken together the data support the hypothesis that the modulation of
      Na channel expression by apical vesicular membrane movements plays a role in Na
      transport expression and its regulation by ADH.

PMID- 7563023
TI  - Small-conductance chloride channels in human peripheral T lymphocytes.
AB  - During whole-cell patch-clamp recording from normal (nontransformed) human T
      lymphocytes a chloride current spontaneously activated in > 98% of cells (n >
      200) in the absence of applied osmotic or pressure gradients. However, some
      volume sensitivity was observed, as negative pressure pulses reduced the current.
      With iso-osmotic bath and pipette solutions the peak amplitude built up (time
      constant approximately 23 sec at room temperature), a variable-duration plateau
      phase followed, then the current ran down spontaneously (time constant
      approximately 280 sec). The anion permeability sequence, calculated from reversal
      potentials was I-, Br- > NO3-, Cl- > CH3SO3-, HCO3- > CH3COO- > F- > aspartate,
      gluconate, SO4(2-) and there was no measurable monovalent cation permeability.
      The Cl- current was independent of time during long voltage steps and there was
      no evidence of voltage-dependent gating; however, the current showed intrinsic
      outward rectification in symmetrical Cl- solutions. The conductance of the
      channels underlying the whole-cell current was calculated from fluctuation
      analysis, using power-spectral density and variance-vs.-mean analysis. Both
      methods yielded a single channel conductance of about 0.6 pS at -70 mV (close to
      the normal resting potential of T lymphocytes). The power spectral density
      function was best fit by the sum of two Lorentzian functions, with corner
      frequencies of 30 and 295 Hz, corresponding to mean open times of 0.54 and 5.13
      msec. The pharmacological profile included rapid block by external application of
      flufenamic acid (50 microM), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB,
      100 microM), [6,7-dichloro-2-cyclopentyl-2,3- dihydro-2-methyl-1-oxo-1H-inden-5
      yl)oxy] acetic acid (IAA-94, 250 microM) or 100 microM 1,9-dideoxyforskolin. The
      stilbene derivatives DIDS (4,4'-diisothiocyano-2,2' disulphonic acid stilbene,
      500 microM) and SITS (4-acetamido-4'-isothiocyano-2,2'-disulphonic acid stilbene,
      500 microM) prevented buildup of Cl- current after a 30-min preincubation at 500
      microM. When tested in a mitogenic assay, DIDS, flufenamic acid, NPPB and IAA-94
      all inhibited T-cell proliferation, suggesting a physiological function in
      addition to the observed volume sensitivity.

PMID- 7563024
TI  - Modulation of neuronal calcium channels by arachidonic acid and related
      substances.
AB  - Low-voltage-activated (l-v-a) and high-voltage-activated (h-v-a) Ca2+ currents
      (ICa) were recorded in whole-cell voltage clamped NG108-15 neuroblastoma x glioma
      hybrid cells. We studied the effects of arachidonic acid (AA), oleic acid,
      myristic acid and of the positively charged compounds tetradecyltrimethylammonium
      (C14TMA) and sphingosine. At pulse potentials > -20 mV, AA (25-100 microM)
      decreased l-v-a and h-v-a ICa equally. The decrease developed slowly and became
      continually stronger with increasing time of application. It was accompanied by a
      small negative shift and a slight flattening of the activation and inactivation
      curves of the l-v-a ICa. The shift of the activation curve manifested itself in a
      small increase of l-v-a ICa at pulse potentials < -30 mV. The effects were only
      partly reversible. The AA effect was not prevented by 50 microM 5, 8, 11, 14
      eicosatetraynoic acid, an inhibitor of the AA metabolism, and not mimicked by 0.1
      1 microM phorbol 12, 13-dibutyrate, an activator of protein kinase C. Probably,
      AA directly affects the channel protein or its lipid environment. Oleic and
      myristic acid acted similarly to AA but were much less effective. The positively
      charged compounds C14TMA and sphingosine had a different effect: They shifted the
      activation curve of l-v-a ICa in the positive direction and suppressed l-v-a more
      than h-v-a ICa; their effect reached a steady-state within 5-10 min and was
      readily reversible. C14TMA blocked l-v-a ICa with an IC50 of 4.2 microM while
      sphingosine was less potent.

PMID- 7563025
TI  - The role of the proton electrochemical gradient in the transepithelial absorption
      of amino acids by human intestinal Caco-2 cell monolayers.
AB  - We determined the extent of Na(+)-independent, proton-driven amino acid transport
      in human intestinal epithelia (Caco-2). In Na(+)-free conditions, acidification
      of the apical medium (apical pH 6.0, basolateral pH 7.4) is associated with a
      saturable net absorption of glycine. With Na(+)-free media and apical pH set at
      6.0, (basolateral pH 7.4), competition studies with glycine indicate that
      proline, hydroxyproline, sarcosine, betaine, taurine, beta-alanine, alpha
      aminoisobutyric acid (AIB), alpha-methylaminoisobutyric acid (MeAIB), tau-amino-n
      butyric acid and L-alanine are likely substrates for pH-dependent transport in
      the brush border of Caco-2 cells. Both D-serine and D-alanine were also
      substrates. In contrast leucine, isoleucine, valine, phenylalanine, methionine,
      threonine, cysteine, asparagine, glutamine, histidine, arginine, lysine,
      glutamate and D-aspartate were not effective substrates. Perfusion of those amino
      acids capable of inhibition of acid-stimulated net glycine transport at the brush
      border surface of Caco-2 cell monolayers loaded with the pH-sensitive dye 2',7'
      bis(2-carboxyethyl-5(6)-carboxyfluorescein) (BCECF) caused cytosolic
      acidification consistent with proton/amino acid symport. In addition, these amino
      acids stimulate an inward short-circuit current (Isc) in voltage-clamped Caco-2
      cell monolayers in Na(+)-free media (pH 6.0). Other amino acids such as leucine,
      isoleucine, phenylalanine, tryptophan, methionine, valine, serine, glutamine,
      asparagine, D-aspartic acid, glutamic acid, cysteine, lysine, arginine and
      histidine were without effect on both pHi and inward Isc. In conclusion, Caco-2
      cells express a Na(+)-independent, H(+)-coupled, rheogenic amino acid transporter
      at the apical brush-border membrane which plays an important role in the
      transepithelial transport of a range of amino acids across this human intestinal
      epithelium.

PMID- 7563022
TI  - The inositol 1,4,5-trisphosphate (InsP3) receptor.

PMID- 7563027
TI  - Regulation of calcium-activated nonselective cation channel activity by cyclic
      nucleotides in the rat insulinoma cell line, CRI-G1.
AB  - The regulation of a calcium-activated nonselective cation (Ca-NS+) channel by
      analogues of cyclic AMP has been investigated in the rat insulinoma cell line,
      CRI-G1. The activity of the channel is modulated by cyclic AMP in a complex way.
      In the majority of patches (83%) tested concentrations of cyclic AMP of 10 microM
      and above cause an inhibition of channel activity which is immediately reversible
      on washing. In contrast, lower concentrations of cyclic AMP, between 0.1 and 1.0
      microM, produce a transient activation of channel activity in most patches (63%)
      tested. One group of analogues, including N6-monobutyryl cyclic AMP and N6, 2'-O
      dibutyryl cyclic AMP reduced the activity of the Ca-NS+ channel at all
      concentrations tested and 2'-O-Monobutyryl cyclic AMP produced inhibition in all
      patches tested except one, at all concentrations. A second group produced dual
      concentration-dependent effects on Ca-NS+, low concentrations stimulating and
      high concentrations inhibiting channel activity. 6-Chloropurine cyclic AMP and 8
      bromo cyclic AMP produced effects similar to those of cyclic AMP itself. In
      contrast, 8-[4-chlorophenylthio] cyclic AMP also showed a dual action, but with a
      high level of activation at all concentrations tested up to 1 mM. Ca-NS+ channel
      activity was also predominantly activated by low concentrations of Sp-cAMPS. The
      activating effects of both Sp-cAMPS and cyclic AMP are antagonized by Rp-cAMPS,
      which by itself only produced a weak inhibition of Ca-NS+ channel activity even
      at concentrations of 10 microM and above. The results are discussed in terms of a
      model in which cyclic AMP, and other cyclic nucleotides, modulate the activity of
      the Ca-NS+ channel by binding to two separate sites.

PMID- 7563026
TI  - Use of 82Br- radiotracer to study transmembrane halide flux: the effect of a
      tranquilizing drug, chlordiazepoxide on channel opening of a GABAA receptor.
AB  - We used the short-lived radionuclide, 82Br- to follow gamma-aminobutyrate (GABA)
      receptor-mediated halide exchange into membrane vesicles from rat cerebral cortex
      in millisecond and second time regions using quench-flow technique. The
      radioisotope was prepared by neutron capture [81Br-(n,gamma)82Br-] on irradiation
      of a natural isotope of bromine, 81Br- in a neutron flux. 82Br- decays by beta
      emission with secondary gamma-emission. Possible advantages of 82Br- over 36Cl-
      in anion tracer measurements include, (a) a short lifetime (t1/2 = 35.3 hr),
      which alleviates contamination and disposal problems, (b) high counting
      efficiency (1.54) due to the secondary radiation, (c) measurement with a gamma
      counter as well as a beta-counter, (d) a simple preparation not requiring
      subsequent purification steps giving a specific activity depending on the
      irradiation time. With 6 hr irradiation time the specific activity was sufficient
      to make measurements with < 1 mM Br-, which is less than the bromide
      concentration known to affect the properties of GABAA receptor. The radiotracers,
      82Br- and 36Cl- could be compared with the same solution composition. In
      conditions where a direct effect of binding of halide to receptor does not
      contribute to a difference in measured ion-flux, 82Br- was translocated only
      marginally faster than 36Cl-. The effect of chlordiazepoxide (CDPX) (2-250
      microM) on the progress of GABA (10 microM)-mediated 82Br- uptake was measured in
      a time range of 200 msec to 20 sec using quench-flow technique. The two phases of
      anion exchange previously reported in this experimental model with GABA alone
      were observed. The rate of 82Br- exchange was increased 2.3-fold at 30-60 microM
      CDPX and was not further increased with increasing [CDPX]. The rate of halide
      exchange is a measure of open channel concentration. The isotope exchange rate
      constant, J, in a membrane vesicle preparation, is a measure of the membrane
      permeability per internal volume/surface area, J = PmA/V. Receptor
      desensitization rate was also increased by CDPX, but unlike the isotope exchange
      rate, it continued to increase up to at least 250 microM CDPX.

PMID- 7563028
TI  - Exogenous GABA persistently opens Cl- channels in cultured embryonic rat thalamic
      neurons.
AB  - We recorded whole-cell Cl- currents in cultured embryonic rat thalamic neurons by
      brief applications of GABA or the structural analogue muscimol. In 17 of 141
      neurons (12%) the Cl- current persisted for a minute or more after the pipette
      was removed from the bath. Cl- current never persisted after muscimol exposure
      even in those cells exhibiting persistent GABA-activated currents (PGC). The half
      decay times (T50) of PGCs were exponentially and asymptotically related to the
      duration of GABA exposure and could be interrupted or completely aborted by low
      pressure application of saline. PGCs were insensitive to membrane potential, to
      Tiagabine, a nipecotic acid analogue known to block GABA uptake, and persisted in
      Cao(2+)-free medium. Fluctuation analysis revealed that PGCs exhibited inferred
      Cl- channel properties whose kinetic components and estimated average elementary
      conductance showed no significant difference from those estimated during GABA
      exposure. The relative contribution of low frequency components was consistently
      reduced and that of high frequency components modestly increased during PGC
      compared to those recorded during GABA exposure. Taken together, the results
      suggest the existence of a superficial compartment in these embryonic neurons
      that can momentarily accumulate and release exogenous GABA.

PMID- 7563029
TI  - Detection of different adenosine triphosphatases in human placental brush border
      membranes.
AB  - The microvillous membrane of human placental syncytiotrophoblast cells contains a
      high ATPase activity. The purpose of this study was to characterize this activity
      and to investigate the presence of vacuolar type H+ ATPase in this membrane.
      Intact brush border membrane vesicles strongly hydrolyzed ATP, reflecting the
      presence of ATPase on the external side of the membrane. The ATPase activity was
      entirely Mg2+ dependent and increased with pH. At pH 7.5, Vmax was 31.0 +/- 1.7
      mumol/mg/20 min and Km 0.18 +/- 0.03 mM ATP. Hydrolysis of ATP was not influenced
      by the presence of bicarbonate or alkaline phosphatase inhibitors, but at pH 8 it
      decreased by half following addition of 100 microM dicyclohexylcarbodiimide
      (DCCD). At pH 7.5, 1 mM N-ethylmaleimide (NEM) depressed this activity by less
      than 5%. Opening the membrane vesicles with 0.1% desoxycholate (DOC) or Triton-X
      neither revealed any additional ATPase activity nor altered the low sensitivity
      to NEM. Treatment of these membranes with 1% cholate decreased the ATPase
      activity by more than 70% and did not enhance the sensitivity of ATP hydrolysis
      to NEM. 10(-7) M Bafilomycin, which reduced by 56 +/- 9% the ATPase activity in
      dog kidney brush border membranes treated with 0.1% DOC, had no effect on
      placental brush border membranes subjected to the same procedure. Finally,
      neither immunocytochemical staining using monoclonal antibody to the M(r) 31000
      subunit of V-type H+ ATPase, nor electron microscopic examination detected the
      presence of H(+) ATPase in placental membranes. In conclusion, the placental
      brush border membrane is the site of a strong "ecto" ATPase activity which is
      partially DCCD sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563030
TI  - Ouabain resistance of the epithelial cell line (Ma104) is not due to lack of
      affinity of its pumps for the drug.
AB  - Na+, K(+)-pumps of most eukaryotic animal cells bind ouabain with high affinity,
      stop pumping, and consequently loose K+, detach from each other and from the
      substrate, and die. Lack of affinity for the drug results in ouabain resistance.
      In this work, we report that Ma104 cells (epithelial from Rhesus monkey kidney)
      have a novel form of ouabain-resistance: they bind the drug with high affinity
      (Km about 4 x 10(-8) M), they loose their K+ and stop proliferating but, in spite
      of these, up to 100% of the cells remain attached in 1.0 microM ouabain, and 53%
      in 1.0 mM. When 4 days later ouabain is removed from the culture medium, cells
      regain K+ and resume proliferation. Strophanthidin, a drug that attaches less
      firmly than ouabain, produces a similar phenomenon, but allows a considerably
      faster recovery. This reversal may be associated to the fact that, while in
      ouabain-sensitive MDCK cells Na+, K(+)-ATPases blocked by the drug are retrieved
      from the plasma membrane, those in Ma104 cells remain at the cell-cell border, as
      if they were cell-cell attaching molecules. Cycloheximide (10 micrograms/ml) and
      chloroquine (10 microM) impair this recovery, suggesting that it also depends on
      the synthesis and insertion of a crucial protein component, that may be different
      from the pump itself. Therefore ouabain resistance of Ma104 cells is not due to a
      lack of affinity for the drug, but to a failure of its Na+, K(+)-ATPases to
      detach from the plasma membrane in spite of being blocked by ouabain.

PMID- 7563031
TI  - A novel type of cell-cell cooperation between epithelial cells.
AB  - Ma104 cells (renal, epithelial) have a peculiar way of resisting ouabain: their
      Na+,K(+)-pumps bind the drug with high affinity, cellular K+ is lost and cell
      division arrested, but cells do not detach as most cell types do. Then, if up to
      4 days later the drug is removed, Ma104 cells recover K+ and resume proliferation
      (Contreras et al., 1994). In the present work, we investigate whether Ma104 cells
      are able to protect ouabain-sensitive MDCK cells in co-culture. The main finding
      is that they do, but in this case protection is not elicited by the usual
      mechanism of maintaining the K+ content of neighboring cells through cell-cell
      communications. Ma104 cells treated with ouabain simply remain attached to the
      substrate and to their MDCK neighbors, and both cells lose K+. This attachment
      includes tight junctions, because the transepithelial electrical resistance of
      the monolayers is not abolished by ouabain. Although the beta-subunit of the
      Na+,K(+)-ATPase is known to possess molecular characteristics of cell-cell
      attachment molecules, attachment between Ma104-MDCK cells does not seem to be
      mediated by this enzyme, as immunofluorescence analysis reveals that Na+,K(+)
      ATPase is only inserted in the plasma membrane facing a neighboring cell of the
      same type.

PMID- 7563033
TI  - Extracellular pH modulates the Ca2+ current activated by depletion of
      intracellular Ca2+ stores in human macrophages.
AB  - Intracellular Ca2+ (Ca(i)) signaling following the binding of surface receptors
      activates a Ca2+ permeable plasma membrane conductance which has been shown to be
      associated with store depletion in a number of cell types. We examined the
      activation of this conductance in human monocyte-derived macrophages (HMDMs)
      using whole-cell voltage-clamp techniques coupled with fura-2 microfluorimetry
      and characterized the importance of external pH (pHo) as a modulator of current
      amplitude. Current activation was observed following experimental maneuvers
      designed to deplete intracellular Ca(2+)-stores including: (i) dialysis of the
      cell with 100 microM inositol 1,4,5-triphosphate (IP3), (ii) intracellular
      dialysis with high concentrations of the Ca2+ buffers EGTA and BAPTA, or (iii)
      exposure of the cell to the Ca(2+)-ATPase inhibitor thapsigargin (1 microM).
      Currents associated with store depletion were inwardly rectifying with kinetics,
      inactivation, and selectivity that appeared similar irrespective of the mode of
      activation. Currents were Ca2+ selective with a selectivity sequence of Ca2+ >
      Sr2+ >> Mg2+ = Mn2+ = Ni2+. The Ca2+ influx current was modulated by changes in
      pHo; modulation was not produced as a consequence of changes in internal pH
      (pHi). External acidification led to a reversible reduction in current amplitude
      with a pKa at pH 8.2. Changes in pHo alone failed to induce current activation.
      These observations are consistent with a scheme by which changes in pHo, as would
      be encountered by macrophages at sites of inflammation, could change the time
      course and magnitude of the Cai transient associated with receptor activation by
      regulating the influx of Ca2+ ions.

PMID- 7563034
TI  - Preparation, characterization, and structure of half gap junctional layers split
      with urea and EGTA.
AB  - Gap junctions, collections of membrane channels responsible for intercellular
      communication, contain two paired hemichannels (also called connexons). We have
      investigated conditions for splitting the membrane pair using urea. We have
      developed a protocol which consistently splits the gap junction samples with 60
      90% efficiency. Our results indicate that hydrophobic forces are important in
      holding the two connexons together but that Ca2+ ions are also important in the
      assembly of the membrane pair. Greater yields and better structural integrity of
      split junctions were obtained with a starting preparation of gap junctions which
      had been detergent treated. Image analysis of edge views of single connexon
      layers reveal an asymmetry in the appearance of the cytoplasmic and extracellular
      surface. Cryo-electron microscopy and image analysis of split junctions show that
      the packing and structural detail of membranes containing arrays of single
      connexons are the same as for intact junctions, and that the urea treatment
      causes no gross structural changes in the connexon assembly.

PMID- 7563032
TI  - Lipids in biological membrane fusion.

PMID- 7563035
TI  - A calcium-activated and nucleotide-sensitive nonselective cation channel in M-1
      mouse cortical collecting duct cells.
AB  - We recently reported that M-1 mouse cortical collecting duct cells show
      nonselective cation (NSC) channel activity (Proc. Natl. Acad. Sci. USA 89:10262
      10266, 1992). In this study, we further characterize the M-1 NSC channel using
      single-channel current recordings in excised inside-out patches. The M-1 NSC
      channel does not discriminate between Na+, K+, Rb+, Cs+, and Li+. It has a linear
      I-V relation with a conductance of 22.7 +/- 0.5 pS (n = 78) at room temperature.
      The Pcation/P(anion) ratio is about 60 and there is no measurable conductance for
      NMDG, Ca2+, Ba2+, and Mn2+. Cytoplasmic calcium activates the M-1 NSC channel at
      a threshold of 10(-6) M and depolarization increases channel activity (NPo).
      Cytoplasmic application of adenine nucleotides inhibits the M-1 NSC channel. At
      doses of 10(-4) M and 10(-3) M, ATP reduces NPo by 23% and 69%, respectively.
      Furthermore, since ADP (10(-3) M) reduces NPo by 93%, the inhibitory effect of
      adenine nucleotides is not dependent on the presence of a gamma-phosphoryl group
      and therefore does not involve protein phosphorylation. The channel is not
      significantly affected by 8-Br-cGMP (10(-4) M) or by cGMP-dependent protein
      kinase (10(-7) M) in the presence of 8-Br-cGMP (10(-5) M) and ATP (10(-4) M). The
      NSC channel is not sensitive to amiloride (10(-4) M cytoplasmic and/or
      extracellular) but flufenamic acid (10(-4) M) produces a voltage-dependent block,
      reducing NPo by 35% at depolarizing voltages and by 80% at hyperpolarizing
      voltages. We conclude that the NCS channel of M-1 mouse cortical collecting duct
      cells belongs to an emerging family of calcium-activated and nucleotide-sensitive
      nonselective cation channels. It does not contribute to amiloride-sensitive
      sodium absorption and is unlikely to be a major route for calcium entry. The
      channel is normally quiescent but may be activated under special physiological
      conditions, e.g., during volume regulation.

PMID- 7563036
TI  - Mechanisms of cell volume regulation in the proximal segment of the Malpighian
      tubule of Rhodnius neglectus.
AB  - The cell volume regulation of the lower segment cells of the Malpighian tubule of
      Rhodnius neglectus in anisosmotic media was evaluated by using video-optic
      techniques. When the medium osmolality was increased with addition of 100 mM
      mannitol the cells shrank to a minimum of 16.84 +/- 2.62% and subsequently
      swelled towards their initial volume undergoing a typical regulatory volume
      increase (RVI). Replacement of either K+ or Cl- or HCO(3-) by Na+, gluconate and
      phosphate, respectively, abolished the RVI response. Furthermore, the
      substitution of Na+ by tetramethylammonium (TMA+) in isosmotic conditions led to
      cellular swelling and death. Addition of either amiloride 10(-4) M, anthracene-9
      COOH 5 x 10(-4) M, furosemide 5 x 10(-4) M or ethacrynic acid 5 x 10(-5) M, also
      abolished RVI. On the other hand, addition of either Ba2+ 10(-3) M, SITS 5 x 10(
      4) M, ouabain 10(-3) M or vanadate 10(-3) M, did not change the RVI response.
      When the tubules were incubated in hyperosmotic media with EGTA 2 mM or verapamil
      10(-6) M, the RVI response was abolished. In contrast, a decrease of NaCl
      concentration from 129 to 79 mM induced a cell swelling to a maximum of 33.11 +/-
      1.73%, but the cells maintained swollen, only partially regulating their volume.
      These results show that the proximal cells of Malpighian tubule of R. neglectus
      are able to regulate their volume in hyperosmotic but only partially regulating
      in hyposmotic solutions. The mechanisms in RVI involve Na+, K+, Cl-, Ca2+ and
      HCO(3-) transport pathways and a ouabain-insensitive ATPase stimulated by Na+.

PMID- 7563037
TI  - Kinetic analysis of two simultaneously activated K+ currents in root cell
      protoplasts of Plantago media L.
AB  - Two different, simultaneously activated outward rectifying K+ currents were
      analyzed in the plasmalemma of root cortex protoplasts of Plantago media. Their
      gating is dependent on the diffusion potential for K+(EK). The threshold
      potential was more negative than EK allowing small inward currents at potentials
      below EK thereby keeping cells with little pump activity in the K state
      (Vogelzang & Prins, 1994). Time and voltage dependence of the outward rectifying
      K+ currents have been analyzed with Hodgkin-Huxley-like (HH) models. Dynamic
      responses of whole cell currents to pulse potentials were analyzed with two
      voltage dependent functions, the Boltzmann distribution for open probability per
      gate and the transition rate towards the open state (alpha). The transition rate
      in the opposite direction (beta), was calculated from alpha and the Boltzmann
      distribution. These functions were used for an integral analysis of activation
      and deactivation currents measured over a range of pulse potentials. Both whole
      cell and single channel data were used for the determination of the number of
      closed and open states. The effects of single channel flickering on time response
      and amplitude of tail currents were added to the model. The dominant K+ channel
      present in the plasmalemma of P. media has a characteristic nonlinear single
      channel I-V curve reducing the amplitude of whole cell currents at positive
      potentials. To compensate for this nonlinearity, a four state translocator model
      was added to the whole cell open probability model. The analysis presented here
      provides a general basis for the study and comparison of K+ channel kinetics in
      plant protoplasts.

PMID- 7563038
TI  - Voltage-dependent sodium currents recorded from dissociated rat taste cells.
AB  - Voltage-dependent sodium currents were analyzed in detail from dissociated
      mammalian taste receptor cells using the whole-cell patch clamp technique.
      Approximately 50-75% of all taste receptor cells expressed sodium currents. These
      currents activated close to -50 mV (holding potential = -80 mV) with maximal
      currents most often occurring at -10 mV. The distribution of maximal inward
      currents across all cells appeared to display two peaks, at -254 pA and -477 pA,
      possibly due to differences in sodium channel density. Inward currents were
      eliminated by replacing 90% of external sodium with N-methyl-D-l-glucamine. The
      current-voltage relationship of the activated current, as measured by a tail
      current analysis, was linear, suggesting an ohmic nature of the open channel
      conductance. The relationship between the time to the peak activated current and
      the step potential was well fit by a double exponential curve (tau1 = 6.18, tau2
      = 37.8 msec). Development of inactivation of the sodium current was dependent
      upon both voltage- and temporal-parameters. The voltage dependence of the time
      constant (tau) obtained from removal of inactivation, development of
      inactivation, and decay of the sodium current displayed a bell-shaped curve with
      a maximum of 55 msec at -70 mV. In addition to fast inactivation (half maximal at
      -50 mV), these currents also displayed a slow inactivation (half maximal at -65
      mV). Voltage-dependent sodium currents were reversibly inhibited by nanomolar
      concentrations of tetrodotoxin (Kd = 10(-8) M). There was no evidence of a TTX
      insensitive sodium current. This description broadens our understanding of
      gustatory transduction mechanisms with a particular relevance to the
      physiological role of receptor cell action potentials.

PMID- 7563039
TI  - Thermodynamically specific gating kinetics of cardiac mammalian K+(ATP) channels
      in a physiological environment near 37 degrees C.
AB  - Elementary K+ currents through isolated ATP-sensitive K+ channels from neonatal
      rat cardiocytes were recorded to study their temperature dependence between 9
      degrees C and 39 degrees C. Elementary current size and, thus, K+ permeation
      through the open pore varied monotonically with temperature with a Q10 of 1.25
      corresponding to a low activation energy of 3.9 kcal/mol. Open-state kinetics
      showed a complicated temperature dependence with Q10 values of up to 2.94.
      Arrhenius anomalies of tau(open)(1) and tau(open)(2) indicate the occurrence of
      thermally-induced perturbations with a dominating influence on channel portions
      that are involved in gating but are obviously ineffective in altering pore
      forming segments. At 39 degrees C, open-state exit reactions were associated with
      the highest activation energy (O2 exit reaction: 12.1 kcal/mol) and the largest
      amount of entropy. A transition from 19 degrees C to 9 degrees C elucidated a
      paradoxical kinetic response, shortening of both O-states, irrespective of the
      absence or presence of cAMP-dependent phosphorylation. Another member of the K+
      channel family and also a constituent of neonatal rat cardiocyte membranes, 66 pS
      outwardly-rectifying channels, was found to react predictably since tau(open)
      increased on cooling. Obviously, cardiac K+(ATP) channels do not share this
      exceptional kinetic responsiveness to a temperature transition from 19 degrees C
      to 9 degrees C with other K+ channels and have a unique sensitivity to thermally
      induced perturbations.

PMID- 7563040
TI  - Ca2+ modulation of sarcoplasmic reticulum Ca2+ release in rat skeletal muscle
      fibers.
AB  - Ca2+ transients and the rate of Ca2+ release (dCaREL/dt) from the sarcoplasmic
      reticulum (SR) in voltage-clamped, fast-twitch skeletal muscle fibers from the
      rat were studied with the double Vaseline gap technique and using mag-fura-2 and
      fura-2 as Ca2+ indicators. Single pulse experiments with different returning
      potentials showed that Ca2+ removal from the myoplasm is voltage independent.
      Thus, the myoplasmic Ca2+ removal (dCaREM/dt) was studied by fitting the decaying
      phase of the Ca2+ transient (Melzer, Rios & Schneider, 1986) and dCaREL/dt was
      calculated as the difference between dCa/dt and dCaREM/dt. The fast Ca2+ release
      decayed as a consequence of Ca2+ inactivation of Ca2+ release. Double pulse
      experiments showed inactivation of the fast Ca2+ release depending on the
      prepulse duration. At constant interpulse interval, long prepulses (200 msec)
      induced greater inactivation of the fast Ca2+ release than shorter
      depolarizations (20 msec). The correlation (r) between the myoplasmic [Ca2+]i and
      the inhibited amount of Ca2+ release was 0.98. The [Ca2+]i for 50% inactivation
      of dCaREL/dt was 0.25 microM, and the minimum number of sites occupied by Ca2+ to
      inactivate the Ca2+ release channel was 3.0. These data support Ca2+ binding and
      inactivation of SR Ca2+ release.

PMID- 7563041
TI  - Reduced ambulatory heart rate response to physical work and complaints of fatigue
      among hypertensive males treated with beta-blockers.
AB  - Treatment with beta-blockers affects oxygen metabolism and lipolysis during
      physical exertion. Together with possible central nervous system effects, this
      may impair the work capacity of treated hypertensive subjects. In a study of 1619
      male employees, aged 45-64 years, mean resting and ambulatory heart rate (HR) and
      complaints of fatigue were compared between hypertensive workers treated with
      beta-blockers and untreated hypertensives and normotensives under low and high
      workload conditions. Treated hypertensives had lower mean resting HRs compared
      with normotensives and untreated hypertensives. Their change from resting to
      ambulatory HR during low and high workload was also lower than normotensives and
      untreated hypertensives, and they had higher fatigue scores than their untreated
      counterparts at both workload levels. The highest fatigue score was reported by
      treated subjects under high workload. These findings demonstrate a reduced HR
      response to physical work accompanied by more symptoms of fatigue during
      treatment with beta-blockers. When hypertensives are engaged in physically
      demanding work, other classes of antihypertensive therapy should be considered.

PMID- 7563042
TI  - Psychoactive medication, alcohol use, and falls among older adults.
AB  - The purposes of this study were to determine: (1) the prevalence of psychoactive
      medication and alcohol use and (2) the relationship among psychoactive
      medications, alcohol use, and falls in a sample of 1028 independently living
      women and men, aged 55 and older. Twenty-six percent of the sample reported
      falling, 28% were taking one or more psychoactive drugs, and 38% drank alcohol
      during the past year. Analyses with logistic regression indicate that predictors
      of falls were psychoactive drug use, age, and number of illnesses. Living alone,
      frequency of alcohol use, and gender were not significant predictors.

PMID- 7563044
TI  - Effect of binge eating on the prediction of weight loss in obese women.
AB  - Factors that may be associated with successful weight loss in the obese are of
      clinical and theoretical significance. Although perceived behavioral control
      (PBC) had been shown to predict weight loss in a nonclinical population, it had
      not been used to predict weight loss in the obese. We studied obese women
      enrolled in a 15-week structured weight loss program and hypothesized that PBC
      would predict weight loss for low binge eaters better than for high binge eaters.
      Results indicated that the ability of PBC to predict weight loss immediately
      posttreatment and 6 months posttreatment depended on binge eating severity,
      whereas prediction of group attendance was independent of binge eating status.

PMID- 7563043
TI  - Cardiovascular reactivity and positive/negative affect during conversations.
AB  - Systolic and diastolic blood pressures (SBP, DBP) were measured for 70 college
      students before, during and after informal dyadic conversations. Participants
      rated the positive and negative affect they experienced during conversation. SBP
      and DBP increased significantly from baseline to conversation. Increases in SBP
      and DBP were associated with more positive affect and unrelated to negative
      affect. Blood pressure measures taken one week later provided a more useful
      assessment of resting levels than measures taken before the conversation.
      Relationships between BP reactivity and positive affect remained significant
      after controlling for resting levels of BP, amount of talk during conversation,
      and sex of speaker in hierarchical regression. Blood pressure elevation during
      social interaction may be associated with involvement or enthusiasm, rather than
      emotional distress; this association is not simply an artifact of talkativeness.
      We suggest that cardiovascular reactivity in healthy young adults engaged in
      nonthreatening conversations may be a widespread phenomenon and not necessarily
      pathological.

PMID- 7563045
TI  - Effect of interventions on stage of mammography adoption.
AB  - Mammography has been found significantly to impact mortality in women; however,
      compliance is still problematic. A theoretical model which combined Health Belief
      Model (HBM) constructs with stage of mammography adoption was used to investigate
      the effect of an individualized belief and/or informational intervention on
      mammography compliance. A control group and three intervention groups (belief,
      information, and belief and information) were used. A probability sample of 405
      women ages 40-88 years without a prior history of breast cancer was randomly
      assigned to groups. Subjects in the intervention group received individually
      tailored messages to alter beliefs or provider information related to mammography
      screening. Women in the combined belief/information group were over two times
      more likely to have been compliant with mammography 1 year postintervention than
      those in the control. In addition, groups who received the belief intervention
      had significantly more women that went from a lower to a higher stage of
      mammography adoption.

PMID- 7563046
TI  - Poor sleepers who do not complain of insomnia: myths and realities about
      psychological and lifestyle characteristics of older good and poor sleepers.
AB  - Psychological adjustment, lifestyle, and sleep parameters were investigated in
      634 older community residents. Participants were divided into three categories:
      good sleepers, poor sleepers experiencing high distress, and poor sleepers
      experiencing minimal distress. Results indicate that (1) highly distressed poor
      sleepers manifested an anxious, depressed, negative cognitive-affective set; (2)
      many coped well with age related changes in sleep quality--they resembled good
      sleepers in the relative absence of psychological maladjustment they displayed;
      (3) the three groups had similar lifestyles, but they differed in the cognitive
      affective evaluation of their activities, (4) the insomnia complaint is itself
      multifaceted and is comprised of three distinct elements--difficulty sleeping,
      distress, and daytime fatigue; (5) sleep practices (e.g., naps, bedtimes) are not
      implicated in chronic poor sleep; and (6) many commonly held assumptions about
      sleep disruptions in older individuals are myth rather than reality. Implications
      for better understanding and treating insomnia in older individuals are
      discussed.

PMID- 7563047
TI  - Work, marriage, lifestyle, and changes in men's physical health.
AB  - Using three waves of data for 320 men living in the rural Midwest, this study
      tested a model which proposed independent effects of work conditions and marital
      experiences on change in physical health through health behaviors. The findings
      support the hypothesized model. Both control over work and positive marital
      interactions reduced the probability of a risky lifestyle in terms of health
      related behaviors after controlling for family economic status. Risky lifestyle,
      in turn, was related to poorer self and spouse reported health after controlling
      for previous health status and family income. The findings underscore the
      importance of specific work and marital processes for men's physical health.

PMID- 7563048
TI  - Analysis of action of the wobble adenine on codon reading within the ribosome.
AB  - Computer graphics simulation of the interaction between the codon-anticodon
      duplexes containing adenine in the first (wobble) position of the anticodons, and
      bound to the ribosomal A- and P-sites, was made. This demonstrated that
      widespread use of adenine in the wobble position in anticodons should lead to a
      low efficiency of ribosomal translation, since the wobble A of the P-site tRNA
      weakens the codon-dependent binding of aminoacyl-tRNA at the A-site via
      interduplex interaction. Besides the canonical partner U, the wobble A of
      aminoacyl-tRNA can recognize A, C, G in the third position of the codon by the
      formation of the propeller twist in the wobble pairs AA, AC, AG. The conversion
      of the wobble A into inosine improves its pairing with the codon bases (the pairs
      IA and IC, unlike AA and AC, should not form the propeller twist leading to the
      deformation of base-base hydrogen bonds) and should reduce an adverse effect of
      the P-site wobble adenine on the formation of the A-site duplex. The consequence
      of the interaction between the ribosomal P- and E-site duplexes has been
      formulated. According to this the E-site wobble A should enhance the probability
      of frameshifting. These properties of the wobble A and I could be a reason why A
      is very rarely observed in the first anticodon position and why evolutionary
      processes have developed the enzyme which modifies the wobble A to I. The results
      obtained can be subjected to direct experimental tests.

PMID- 7563049
TI  - A stable interaction between separated pyrimidine.purine tracts in circular DNA.
AB  - Pyrimidine.purine tracts are widespread in eukaryotic genomes and have the
      potential to form a number of unusual structures including triplexes. Two such
      tracts, which could form triplexes with each other but not with themselves, were
      cloned into a plasmid at separate sites. Upon lowering the pH, linear, open
      circular and relaxed plasmid molecules formed a number of novel structures that
      were observed on agarose gels and directly by electron microscopy. In open
      circles a stable join was formed between the two Pyr.Pur tracts giving rise to
      molecules resembling dumbells, trefoils and tetrafoils, which collectively are
      termed T-loops. The structure was stable at pH 8 and contains a single-stranded
      region that was sensitive to P1 nuclease. Thus, there is no apparent topological
      impediment to the formation of triplex-mediated loops in circular molecules.
      These structures may be important for gene regulation and chromosome
      condensation.

PMID- 7563050
TI  - Kinetics of expression of inducible beta-galactosidase in murine fibroblasts:
      high initial rate compared to steady-state expression.
AB  - We have constructed a murine fibroblast cell line in which synthesis of beta
      galactosidase can be induced by incubation with isopropyl-beta-D
      thiogalactopyranoside (IPTG). This was obtained by transfection by both a plasmid
      expressing lacI and a second plasmid expressing lacZ from a modified simian virus
      40 (SV40) promoter containing a lac operator. We have measured the induction
      kinetics as well as the basal and induced differential rate of synthesis of beta
      galactosidase. The steady-state rate of synthesis is tenfold higher in the
      presence than in the absence of inducer; we calculate an average of 1200 lacZ
      polypeptides are synthesized per minute per cell in the induced cultures.
      However, immediately after induction, the rate of accumulation of beta
      galactosidase is up to 50-fold higher than the basal level. Based on our
      measurements of stability of beta-galactosidase, we suggest that induction may
      result in a subsequent down-modulation of the transcriptional activity from the
      induced gene. We hypothesize this inhibition may result from structural changes
      in DNA components, such as nucleosomes.

PMID- 7563051
TI  - Modification of primary structures of hairpin ribozymes for probing active
      conformations.
AB  - Hairpin ribozymes consist of two stem-loop domains, and these domains are assumed
      to interact with each other to produce the self-cleavage activity. We have
      studied the relationship of the tertiary structure of the hairpin ribozyme and
      the cleavage activity by dividing and re-joining the domains. A hairpin ribozyme
      (E50) was divided at the hinge region, and the main part was joined to a
      substrate (S1) using tri- or penta-cytidylates. These ribozymes retained the
      cleavage activity in the presence of the rest of the molecule, indicating that
      the active conformation could be maintained if the two domains interacted with
      each other. Based on the these results, we designed a new type of hairpin
      ribozyme by replacing one of the domains. To maintain the interaction of the
      domains, oligocytidylates were inserted at a junction. These reversely jointed
      ribozyme complexes showed cleavage activity that was dependent on the linker
      lengths. These modifications in the primary structure of the hairpin ribozyme
      confirm the structural requirement for the catalytic reaction and provide
      information for the correlation of the tertiary structure with the cleavage of
      the hairpin ribozyme.

PMID- 7563053
TI  - Determination of the folding topology of the SL1 RNA from Caenorhabditis elegans
      by multidimensional heteronuclear NMR.
AB  - The process of trans-splicing involves the transfer of a short spliced leader
      (SL) RNA sequence to a consensus acceptor site on a separate pre-mRNA transcript.
      In this study, the first stem loop of the SL1 RNA from the nematode
      Caenorhabditis elegans was examined by homonuclear and heteronuclear NMR. Results
      of enzymatic cleavage patterns established that the first 36 nucleotides (which
      includes the splice site and a complementary base-paired region surrounding a
      nine-nucleotide hairpin loop) remain structurally independent of the rest of the
      100-nucleotide full-length transcript. A comparison of exchangeable and non
      exchangeable proton chemical shifts in the region of the splice site and loop
      between the native sequence and a modified 26-nucleotide fragment from which an
      asymmetric internal loop had been deleted was made. There was no significant
      difference between the resonance locations of the equivalent protons in the two
      molecules, establishing that there was no tertiary interaction between the
      hairpin and internal loops. Full chemical shift assignments of 1H, 13C, and 15N
      chemical shifts were obtained for the modified fragment by multidimensional
      homonuclear and heteronuclear NMR spectroscopy. The stem adopts an A-form helix
      typical of RNA. The A-type helical conformation of the stem appears to continue
      for the first three nucleotides of the 5' side of the loop, followed by a
      guanosine residue in a syn conformation about the glycosidic bond. Base stacking
      is not seen on the 3' side of the loop. There was no evidence for formation of
      Watson-Crick base-pairs within the loop, but several long distance NOEs indicated
      cross-loop contacts, indicative of a structured loop. The final loop residues, an
      adenine which is conserved among all known nematode SL RNA sequences, adopts an
      extrahelical conformation.

PMID- 7563052
TI  - Electrostatic mechanism of nucleosome spacing.
AB  - Native bulk chromatin is characterized by regular arrays of nucleosomes with
      defined internucleosomal distances. The nucleosome repeat length is not a
      constant but varies between species and cell-types, during differentiation and
      during gene activation. Previous studies have highlighted the importance of
      linker histones as a major determinant of nucleosome repeat length in vivo. We
      used a physiological reconstitution system derived from Drosophila embryos to
      study nucleosome spacing. In these extracts, histone H1 incorporation increases
      the apparent linker length in a gradual way. Manipulation of the chromatin
      assembly conditions in vitro allowed us to define additional parameters that
      modulate nucleosomal distances, such as protein phosphorylation events and the
      precise ionic conditions during the reconstitution. Interestingly, moderate
      changes in the concentrations of mono-, di-, and multivalent cations affect the
      precise distances between nucleosome cores remarkably. These changes in the ionic
      environment are unlikely to affect the association of linker proteins but are
      known to influence the folding of the nucleosomal fiber by modulation of
      electrostatic forces. Our results suggest electrostatic interactions in chromatin
      units as major determinants of nucleosome spacing. Nucleosome spacing and the
      folding of the nucleosomal fiber can therefore be explained by common principles,
      most notably the neutralization of charges in linker DNA.

PMID- 7563054
TI  - A residue to residue hydrogen bond mediates the nucleotide specificity of
      ribonuclease A.
AB  - Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of the P-O5
      bond of RNA after residues bound in the enzyme's B1 subsite. This subsite binds
      to cytidine 30-fold more tightly than to uridine and > 10(5)-fold more tightly
      than to adenine. Structural studies had suggested that the hydroxyl group of
      Thr45 can interact directly with the base of a bound nucleotide. In contrast, the
      carboxylate group of Asp83 cannot interact directly with bound substrate but can
      accept a hydrogen bond from the hydroxyl group of Thr45. To assess the role of
      the Thr45-Asp83 hydrogen bond in catalysis, T45G, D83A and T45G/D83A RNase A were
      prepared and their abilities to catalyze the cleavage of various substrates were
      determined. The results indicate that the side-chain of Asp83 enhances catalysis
      of reactions in which uridine is bound in the B1 subsite, but that this
      enhancement relies on the side-chain of Thr45. In contrast, the side-chain of
      Asp83 does not contribute to catalysis of reactions with cytidine in the B1
      subsite. Thermodynamic cycles derived from kinetic parameters for the cleavage of
      poly(U) indicate that the Thr45-Asp83 interaction contributes 1.2 kcal/mol to
      transition state stabilization, which is 0.9 kcal/mol greater than its
      contribution to ground state stabilization. Thus, like many residue-substrate
      interactions, this residue to residue interaction enhances catalysis by becoming
      stronger as the reaction approaches the transition state.

PMID- 7563055
TI  - Thermodynamic mapping of the inhibitor site of the aspartic protease
      endothiapepsin.
AB  - The discovery that the protease from the human immunodeficiency virus (HIV)
      belongs to the aspartic protease family has generated renewed interest in this
      class of proteins. In this paper, the interactions of endothiapepsin, an aspartic
      proteinase from the fungus Endothia parasitica, with the inhibitor pepstatin A
      have been studied by high-sensitivity calorimetric techniques. These experiments
      have permitted a complete characterization of the temperature and pH-dependence
      of the binding energetics. The binding reaction is characterized by negative
      intrinsic binding enthalpy and negative heat capacity changes. The association
      constant is maximal at low pH (2 x 10(9) M-1 at pH 3) but decreases upon
      increasing pH (8.1 x 10(6) M-1 at pH 7). The binding of the inhibitor is coupled
      to the protonation of one of the aspartic moieties in the Asp dyad of the
      catalytic site of the protein. This phenomenon is responsible for the decrease in
      the apparent affinity of the inhibitor for the enzyme upon increasing pH. The
      experimental results presented here indicate that the binding of the inhibitor is
      favored both enthalpically and entropically. While the favorable enthalpic
      contribution is intuitively expected, the favorable entropic contribution is due
      to the large gain in solvent-related entropy associated with the burial of a
      large hydrophobic surface, that overcompensates the loss in conformational and
      translational/rotational degrees of freedom upon complex formation. The
      characteristics of the molecular recognition process have been evaluated by means
      of structure-based thermodynamic analysis. Three regions in the protein
      contribute significantly to the free energy of binding: the residues surrounding
      the Asp dyad (Asp32 in the N-terminal lobe and Asp215 in the C-terminal domain)
      and the flap region (Ile73 to Asp77). In addition, the rearrangement of residues
      that are not in immediate contact with the inhibitor provides close to 40% of the
      protease contribution to the binding free energy. On the other hand, the two
      statine residues provide more than half of the inhibitor contributions to the
      total free energy of binding. It is demonstrated that a previously developed
      empirical structural parametrization of the thermodynamic parameters that define
      the Gibbs energy, accurately accounts for the binding energetics and its
      temperature and pH-dependence.

PMID- 7563056
TI  - Free energy determinants of secondary structure formation: I. alpha-Helices.
AB  - The Zimm-Bragg parameters s and sigma are calculated for the helix-coil
      transition of poly-L-alanine. The theoretical approach involves evaluating gas
      phase conformational energies for both coil and helical states using the CHARMM
      potential function and accounting for solvation effects with various continuum
      solvation models. Conformational free energies are then incorporated into a
      formalism developed by Go et al. for the calculation of s and sigma. Calculated
      values for both s and sigma as well as the enthalpy change associated with helix
      formation are in good agreement with experimental data when the Finite Difference
      Poisson-Boltzmann (FDPB) method is used to treat solvent effects. The driving
      force for the helix-coil transition is analyzed in terms of individual free
      energy components. Hydrogen bond formation is found to contribute little to helix
      stability because the internal hydrogen bonding energy is largely canceled by the
      large free energy cost associated with removing polar groups from water. The
      entropic cost associated with fixing backbone dihedral angles in the helical
      conformation is found to be approximately 7 e.u./residue (about 2 kcal/mol at
      room temperature). The major driving force favoring helix formation can be
      associated with interactions including enhanced van der Waals interactions in the
      close-packed helix conformation and the hydrophobic effect. These contribute
      about 2 kcal/mol favoring the helical state. The differences in helical
      propensities between alanine and glycine are attributed primarily to hydrophobic
      and packing interactions involving the C beta with a smaller contribution arising
      from increased conformational freedom for glycine in the coil state. The
      description of helix formation presented here is consistent with previous
      conclusions regarding tertiary structure formation which suggest that hydrophobic
      and close-packed interactions provide stability while hydrogen bond formation
      constitutes a structural constraint imposed by the high free energy cost
      associated with burying unsatisfied hydrogen bonding groups. alpha-Helix
      formation may thus be viewed as a form of hydrophobic collapse constrained by the
      requirement that polar groups be either exposed to solvent or form hydrogen
      bonds. More generally it appears from this study that for a folding model to be a
      realistic, it must properly account for the chemical nature of the polypeptide
      chain, particularly the solvation energetics of amide groups.

PMID- 7563057
TI  - Free energy determinants of secondary structure formation: II. Antiparallel beta
      sheets.
AB  - The factors that determine the stability of antiparallel beta-sheets are
      considered via a theoretical analysis of conformational free energies. A series
      of idealized model polyalanine beta-sheets are built with constraints such that
      the angular geometry of hydrogen bonding varies in the range observed in proteins
      while hydrogen bonding distance remains fixed. The conformations of the sheets
      generated in this way have a broad distribution of twist angles ranging from
      highly twisted left-handed to highly twisted right-handed orientations. The
      association free energies of the sheets are calculated with a gas phase CHARMM
      potential and FDPB/gamma solvation models. Left-handed structures are found to be
      less stable than right handed structures due to intrachain steric hindrance in
      isolated left-handed strands. This explains why antiparallel beta-sheets in
      proteins are invariably twisted in the right-handed direction. The free energy
      surface for right-handed sheets shows particular preference for conformations
      ranging from flat to those that exhibit a pronounced right-handed twist. This
      suggests that antiparallel beta-sheets can adopt a variety of right-handed
      conformations, a result that is consistent with observations on known proteins.
      In parallel with our study of alpha-helices we find that van der Waals and
      hydrophobic interactions are the primary factor stabilizing polyalanine beta
      sheets, while electrostatic interactions including hydrogen bonding are found to
      be destabilizing. However, in contrast to helices, the net change in
      conformational free energy involving only backbone-backbone interactions
      (including beta-carbons) is not sufficient to overcome the loss in
      configurational entropy that accompanies sheet formation. Rather we suggest that
      cross-strand non-polar side-chain-side-chain interactions are essential for sheet
      formation, explaining why large non-polar amino acids have the greatest sheet
      forming propensities. Thus, sheet propensities involve pairwise interactions and
      are expected to be context dependent, as has been observed in recent experiments.

PMID- 7563058
TI  - The avian adenovirus penton: two fibres and one base.
AB  - The penton capsomer of mammalian adenoviruses consists of a trimeric, long and
      thin fibre inserted into a pentameric base. The avian adenoviruses possess a
      penton which presents another symmetry mismatch: each pentameric base is
      associated with two fibres. Here we have studied the morphology of the penton of
      CELO virus, an avian adenovirus, and we have determined the sequence of both
      fibres, one long and one short. The short fibre is probably associated with the
      base in the same way as the mammalian viral fibres and we will discuss how the
      long fibre could be attached. The shafts of all known adenovirus fibres consist
      of a series of 15-residue repeats. The avian virus fibres show a more complicated
      and less regular shaft repeat structure with single, double and triple repeats.
      The sequences of the receptor binding (head) domains of both fibres are very
      different from all other known fibre head domains and very different from each
      other, suggesting that the two fibres might bind to different receptors. The
      genome organization of the sequenced region is rather different from that in
      human adenoviruses. In particular, a region homologous to the human virus E3
      region was not found at the position where it normally occurs in the human virus
      genome.

PMID- 7563059
TI  - The small subunit of the terminase enzyme of Bacillus subtilis bacteriophage SPP1
      forms a specialized nucleoprotein complex with the packaging initiation region.
AB  - Initiation of SPP1 DNA packaging requires the gene 1 and gene 2 products (G1P and
      G2P), which are different subunits of the terminase enzyme. G1P specifically
      recognizes the phage packaging initiation region (pac). The apparent equilibrium
      constant for the G1P-pac-DNA complex was estimated to be 9 nM. DNase I
      footprinting experiments reveal that the pac region can be subdivided into three
      discrete sites (pacL, pacC and pacR). G1P binds co-operatively to the non
      adjacent pacL and pacR sites. Several G1P protomers bind to the target sequences
      which map close to the pac cleavage site (pacC site), but do not overlap with it.
      G1P interacts in a different fashion with the encapsidated (pacR site) and with
      the non-encapsidated (pacL site) end of the phage genome. G1P interaction with
      the intrinsically bent pacL DNA occurs only on one face of the DNA double helix.
      G1P binding to the pacL and in the pacR region results in a DNA loop. Electron
      microscopy of purified G1P shows that the protein is an oligomer in solution. G1P
      binding to the core region of the pacL site could facilitate the formation of a
      higher-order nucleoprotein structure. This specialized complex would allow the
      pac DNA to form a loop between binding sites brought together by interaction with
      G1P. The results presented here suggest that G1P could provide a tool to
      discriminate the first encapsidated end, which contains pacR, from the non
      encapsidated pacL end.

PMID- 7563060
TI  - DNA cleavage at two recognition sites by the SfiI restriction endonuclease: salt
      dependence of cis and trans interactions between distant DNA sites.
AB  - At low ionic strength, the SfiI restriction enzyme cleaved at similar rates both
      supercoiled and linear DNA with two SfiI sites and linear DNA with one SfiI site.
      For the substrates with two sites, the majority of the DNA was converted directly
      to products cut at both sites; the enzyme appears to bind to two sites before
      catalyzing its reactions, looping out the intervening DNA. At high ionic
      strength, linear DNA with one SfiI site was not cut at all, linear DNA with two
      sites was cleaved slowly while supercoiled DNA with two sites was cleaved
      rapidly, though only half of the DNA with two sites was cut at both sites; the
      DNA that had been cut at one site was not cleaved again at the remaining site.
      The singly cut product must therefore have been generated by a reaction
      incorporating both sites. All DNA cleavage reactions by SfiI thus involve the
      tetrameric enzyme bound to two copies of its recognition sequence, but weakened
      DNA-protein interactions at high ionic strength can cause this complex to
      dissociate before cleaving both sites. Intramolecular interactions between
      distant DNA sites are generally thought to be enhanced by supercoiling and to be
      more stable than intermolecular interactions. The preference of SfiI at high
      ionic strength for substrates with two sites over substrates with one site and,
      in the former case, for supercoiled over linear DNA, validates this view. At low
      ionic strength, the similar rates with the different substrates may be due to
      rate-limiting product dissociation.

PMID- 7563061
TI  - X-ray diffraction of scrapie prion rods and PrP peptides.
AB  - Certain neurodegenerative diseases in humans and animals are caused by small
      proteinaceous infectious particles called prions. Limited proteolysis and
      detergent extraction of the prions containing PrPSc generate prion rods that are
      composed of a polypeptide having an apparent molecular mass of 27 to 30 kDa. This
      polypeptide, termed prion protein PrP 27-30, has a ragged N terminus that begins
      at about residue 90, but retains scrapie infectivity. Moreover, the findings in a
      patient having an inherited prion disease of a truncated PrP with its C terminus
      at residue 145 suggest that the residues 90 to 145 may be of particular
      importance in the pathogenesis of prion diseases. To determine the three
      dimensional organization of prion rods and to identify the core region involved
      in amyloid formation, we recorded X-ray diffraction patterns from rods purified
      from scrapie-infected Syrian hamster (SHa) brains which contain PrP 27-30, and
      from synthetic SHaPrP peptides. Three peptides were studied corresponding to
      residues 113 to 120 (peptide A8A, an octamer composed of glycines and alanines),
      109 to 122 (H1, the first predicted alpha-helical region of PrPC), and 90 to 145
      (a 56 residue peptide containing both H1 and the second predicted alpha-helical
      region of PrPC, H2). Electron microscopy, carried out in parallel with the X-ray
      measurements, revealed that all the samples formed linear polymers which were
      approximately 60 to approximately 200 A wide, with fibrillar or ribbon-like
      morphology. Gels and dried preparations of prion rods gave X-ray patterns that
      indicated a beta-sheet conformation, in which the hydrogen bond distance was 4.72
      A and the intersheet distance was 8.82 A. For the three PrP peptides, the
      intersheet spacings varied widely, owing to the side-chains of the residues
      involved in the formation of the beta-sheet interactions, i.e., 5.13 A for A8A,
      5.91 A for lyophilized H1, 7.99 A from solubilized and dried H1 and 9.15 A for
      the peptide SHa 90-145. The intersheet distance of PrP 27-30 was thus within the
      observed range for the peptides, and suggests that the amyloidogenic core of PrP
      is closely modeled by the peptide SHa 90-145.

PMID- 7563062
TI  - Homodimers of chromosomal proteins HMG-14 and HMG-17 in nucleosome cores.
AB  - In this work, we report that nucleosome core particles interact with an equimolar
      mixture of the chromosomal proteins HMG-14 and HMG-17 to form, exclusively,
      complexes containing two molecules of either HMG-14 or HMG-17 (homodimers).
      Analysis of the binding of various mixtures of wild-type proteins and their
      deletion mutants indicates that homodimer formation is not dependent on contacts
      between the nucleosome-bound HMG-14/-17 proteins themselves. We suggest that HMG
      14/-17 proteins in nucleosomes cross-talk by inducing specific allosteric
      transitions in the chromatin subunit.

PMID- 7563063
TI  - Crystal structure of cellular retinoic acid binding protein I shows increased
      access to the binding cavity due to formation of an intermolecular beta-sheet.
AB  - A recombinant form of murine apo-cellular retinoic acid binding protein I (apo
      CRABPI) has been purified and crystallized at pH 5.0, and the crystal structure
      has been refined to an R-factor of 19.6% at a resolution of 2.7 A. CRABPI binds
      all-trans retinoic acid and some retinoic acid metabolites with nanomolar
      affinities. Coordinates of the holo form of CRABP were not available during the
      early stages of the study, and in spite of numerous homologs of known structure,
      phases were not obtainable through molecular replacement. Instead, an
      interpretable electron density map was obtained by multiple isomorphous
      replacement methods after improvement of the heavy-atom parameters with density
      modified trial phases. Two molecules of apo-CRABPI occupy the P3121 asymmetric
      unit and are related by pseudo 2-fold rotational symmetry. Unique conformational
      differences are apparent between the two molecules. In all of the family members
      studied to date, there is a lack of hydrogen bonds between two of the component
      beta-strands resulting in a gap in the interstand hydrogen bonding pattern. In
      the crystallographic dimer described here, a continuous intermolecular beta-sheet
      is formed by using this gap region. This is possible because of an 8 A outward
      maximum displacement of the tight turn between the third and fourth beta-strands
      on one of the molecules. The result is a double beta-barrel containing two apo
      CRABPI molecules with a more open, ligand-accessible binding cavity, which has
      not been observed in other structures of a family of proteins that bind
      hydrophobic ligands.

PMID- 7563064
TI  - The unfolding thermodynamics of c-type lysozymes: a calorimetric study of the
      heat denaturation of equine lysozyme.
AB  - The energetics of the temperature-induced unfolding of equine lysozyme was
      studied calorimetrically and compared with that of two structurally homologous
      proteins: hen egg white lysozyme and alpha-lactalbumin. The structure of each of
      these proteins is characterized by the presence of a deep cleft that divides the
      molecule into two regions called the alpha and beta domains. In equine lysozyme
      and alpha-lactalbumin the latter domain specifically binds Ca2+. It is shown
      that, in contrast to hen egg white lysozyme in which the alpha and beta domains
      unfold as a single cooperative unit, in equine lysozyme the two domains unfold in
      two separate cooperative stages even in the presence of excess Ca2+. The calcium
      binding beta-domain unfolds at a lower temperature and with more extensive heat
      absorption than the alpha-domain. Binding of Ca2+ increases the stability of the
      beta-domain, but even in the holo form it is less stable than the alpha-domain.
      The thermodynamic characteristics of Ca2+ binding have been determined, and
      indicate that it is an entropically driven process. The unfolding of equine
      lysozyme largely resembles the unfolding of alpha-lactalbumin, which also unfolds
      in two stages, but in the latter case the second stage is much less cooperative
      and proceeds with a smaller and diffuse heat absorption. As a result, the total
      enthalpy of unfolding of equine lysozyme is significantly larger than that of
      alpha-lactalbumin, being almost of the same magnitude as the enthalpy of egg
      white lysozyme unfolding, which proceeds as a single two-state transition.
      Analyses of the unfolding enthalpy function of various lysozymes, which bind or
      do not bind Ca2+, and unfold in one or two stages, have led us to the conclusion
      that the main reason for the loss of interdomain cooperativity in equine lysozyme
      is not the cluster of negative charges forming the calcium binding site, but the
      difference in atomic packing in the interior and at the interface between the
      alpha and beta domains.

PMID- 7563065
TI  - Impact of local and non-local interactions on thermodynamics and kinetics of
      protein folding.
AB  - To address the question of how the geometry of a protein's native conformation
      affects its folding and stability, we studied three model 36-mers on a cubic
      lattice. The native structure of one of these model 36-mers consisted mostly of
      local contacts, while that of a second consisted mostly of non-local contacts.
      The third native structure had a typical compact native conformation, and served
      as our reference. For each protein, the amino acid sequence was designed to have
      a pronounced energy minimum at its native conformation. We observed dramatic
      differences in folding, dependent on the presence or absence of non-local
      contacts. For the proteins with a typical large number of non-local contacts, the
      folding transition was all-or-none, whereas for the one with mostly local
      contacts, it was not. Although the maximum rate of folding was similar for all
      three proteins, we found that under conditions at which each native conformation
      was stable, the structure with mostly non-local contacts folded two orders of
      magnitude faster than the one with mostly local contacts. The statistical
      analysis of protein structure agrees fully with the implications of the theory.
      We discuss the importance of cooperativity in protein folding for its stability.

PMID- 7563066
TI  - Proline in a transmembrane helix compensates for cavities in the photosynthetic
      reaction center.
AB  - A site-specific double mutant, in which the large aromatic residues M208Tyr and
      L181Phe in the interior of the photosynthetic reaction center (RC) complex were
      replaced by smaller threonine residues, showed a dramatic reduction in the number
      of assembled complexes and was incapable of photosynthetic growth. The cavity
      created by the smaller side-chains was thought to interfere with the stability
      and/or assembly of the complex. Phenotypic revertants were recovered in which a
      spontaneous second-site mutation restored photocompetence in the presence of the
      original site-specific mutations. In these strains, an Ala-->Pro substitution in
      a neighboring transmembrane helix (at M271) resulted in an increased yield of RC
      complexes. To test the hypothesis that the original phenotype was due to a
      cavity, other mutants were constructed that created similar-sized voids at other
      positions in the membrane-spanning interior. These substitutions caused the same
      phenotype. Coupling of the above proline substitution to these new cavity mutants
      also resulted in photocompetent strains that carry increased levels of RC
      complexes. Therefore, the proline substitution at M271 serves as a global
      suppressor of the phenotype caused by these internal cavities. The proline
      substitution slightly increases the thermal stability of the complex at higher
      temperatures, but the mutant and suppressor strains have about the same stability
      at the optimal culture temperature, where both are less stable than the wild-type
      strain. Therefore, the proline substitution may suppress the non-photosynthetic
      phenotype of cavity mutants by facilitating folding of the nascent polypeptides
      as they assemble with cofactors to form the transmembranar RC complex. The
      proline replacement occurs at a pre-existing kink in a transmembrane helix where
      it can be accommodated without introducing a strain in the structure. The
      function of proline residues in transmembrane helices might be to promote folding
      and/or assembly in general.

PMID- 7563067
TI  - Conformational properties of four peptides spanning the sequence of hen lysozyme.
AB  - Four peptides encompassing the entire amino acid sequence of hen lysozyme were
      examined in aqueous solution and in 50% (v/v) 2,2,2-trifluoroethanol (TFE) by far
      UV CD. Two peptides, 1-40 and 84-129, correspond to regions which are helical in
      the native protein, and together represent the alpha-domain. The beta-domain of
      the native enzyme was also synthesized as two peptides, one (41-60) containing
      the residues in the triple stranded antiparallel beta-sheet and the other (61-82)
      corresponding to a region lacking regular secondary structure. In water at pH 2.0
      and 25 degrees C, the monomeric peptides 1-40, 41-60 and 61-82 appear to be
      predominantly unstructured. By contrast, the peptide 84-129 has considerable,
      presumably helical structure, corresponding to approximately 19%, or nine
      residues, on average, which can be unfolded by the addition of 8 M urea or 6 M
      guanidine hydrochloride. In 50% TFE the conformational properties of the four
      peptides are again distinct. Although little helical structure is induced in the
      peptides 41-60 and 61-82, and a native-like extent of helical structure is
      induced in the peptide 1-40, the peptide 84-29 converts almost entirely to
      helical structure in 50% TFE. The far-UV CD spectrum of a stoichiometric mixture
      of the four peptides in water resembles closely that of a denatured state of the
      intact protein formed by reductive methylation of its four disulphide bonds, but
      differs significantly from that of the native protein. The far-UV CD spectrum of
      the peptide mixture in TFE is indistinguishable from that of the intact protein
      in this solvent, both in the presence and in the absence of its four disulphide
      bonds. The conformational preferences of the peptides are not predicted using
      standard assessments of helical propensity or hydrophobicity, but correlate
      instead with the number of local contacts made in the native protein. On the
      basis of these results, we suggest that the region 84-129 could play an important
      role in determining the nature of the early folding events in the folding pathway
      of the intact polypeptide chain.

PMID- 7563068
TI  - Fluctuation and cross-correlation analysis of protein motions observed in
      nanosecond molecular dynamics simulations.
AB  - Nanosecond molecular dynamics simulations of bovine pancreatic trypsin inhibitor
      and lysozyme in water are analyzed in terms of backbone atomic positional
      fluctuations and dynamical cross-correlations. It is found that although the
      molecular systems are stable, B-factors calculated over a time period as long as
      500 ps are not representative for the motions within the proteins. This is
      especially true for the most mobile residues. On a nanosecond time-scale, the B
      factors calculated from the simulations of the proteins in solution are
      considerably larger than those obtained by structure refinement of the proteins
      in crystals, based on X-ray data. The time evolution of the atomic fluctuations
      shows that for large portions of the proteins under study, atomic positional
      fluctuations are not yet converged after a nanosecond. Cross-correlations do not
      converge faster than the fluctuations themselves. Most display very erratic
      behavior if the sampling covers less than about 200 ps. It is also shown that
      inclusion of mobile atoms into the procedure used to remove rigid-body motion
      from the simulation can lead to spurious correlations between the motions of the
      atoms at the surface of the protein.

PMID- 7563069
TI  - Sequence determinants for -2 frameshift mutagenesis at NarI-derived hot spots.
AB  - The recognition sequence of the NarI restriction enzyme is known to be a strong
      hot spot for -2 frameshift mutations (G1G2CG3CC-->GGCC) induced by the chemical
      carcinogen N-2-acetylaminofluorene (AAF). In an attempt to define a "consensus
      sequence" for this mutation hot spot, we have investigated the role of the bases
      flanking the central dinucleotide GpC repeat in the NarI sequence (NaGCGCNb) on
      the mutation frequency induced by the carcinogen. Construction and random
      modification with AAF of the 16 plasmids resulting from the replacement of Na and
      Nb by A,T,G and C, respectively, have been undertaken. All 16 sequences tested
      are found to be -2 frameshift mutation hot spots. Indeed, a level of modification
      of approximately five AAF adducts per plasmid molecule induces a mutation
      frequency ranging between 500 and 5000-fold above background. The mutations
      observed are mainly (90%) deletion of a dinucleotide CpG in the targeted sequence
      NaGCGCNb. Previous studies on NarI mutagenesis (G1G2CG3CC-->GGCC) have shown that
      only AAF adducts at G3 in the template for lagging strand synthesis induce -2
      frameshift mutagenesis at a high level. When the mutation data obtained in this
      work are analyzed as originating essentially from adducts to guanines in this
      strand, we find that it is the nucleotide Nb located 3' to the central
      dinucleotide GpC repeat that strongly modulates the mutation frequency, while the
      nucleotide Na located on the 5' side has little effect. Our present model of
      frameshift mutagenesis at NarI sites involves a template-primer misalignment step
      with a two-nucleotide slipped mutagenic intermediate. In the context of this
      model, the modulation of mutagenesis by nucleotide Nb located two nucleotides 3'
      from the putative adduct site in the template strand can be explained in view of
      the fact that the replication complex encounters this nucleotide before it
      encounters the adduct.

PMID- 7563070
TI  - Molecular analysis of mutations in the hprt gene of V79 hamster fibroblasts:
      effects of imbalances in the dCTP, dGTP and dTTP pools.
AB  - dCMP-deaminase-deficient V79/dC hamster cells have highly imbalanced
      deoxyribonucleoside triphosphate (dNTP) pools, i.e. a 17-fold larger dCTP pool, a
      slightly reduced dTTP and a very low dGTP pool, compared to dCMP-deaminase
      proficient V79/p cells. Nevertheless, the two lines showed the same rates of
      spontaneous mutation at the hprt and ouabain-resistance loci. Analysis of
      spontaneous hprt mutations indicated an increase in misincorporation of C in
      V79/dC cells, although it was not statistically significant. When the dCTP pool
      was further increased fivefold by incubating V79/dC cells with cytidine, C
      misincorporation increased to 88%, but the mutation frequency remained unchanged.
      The dNTP pools of V79/dC cells were also altered by treatment with thymidine, or
      with thymidine plus deoxycytidine. After incubation with thymidine alone, the
      dCTP pool all but disappeared, whereas it maintained a normal level in the
      presence of deoxycytidine. In both cases dTTP rose to nmol amounts, and dGTP
      accumulated. Incubation with 10 mM thymidine was the only treatment that
      increased the mutation frequency; T misincorporation then accounted for 94% of
      the base substitutions. In the presence of deoxycytidine the cells had a
      dTTP/dCTP ratio of 0.04, but 86% of the base substitutions involved C
      misincorporation and most probably originated from G mis-incorporation caused by
      excess dGTP. Alterations of RNA splicing and hot spots for base substitutions
      varied with the imbalance, the latter showed "next-nucleotide effects". Our
      results suggest that the fidelity of DNA replication in V79 cells is only
      affected by large changes in the pool and is more sensitive to changes in dGTP
      than in dCTP or dTTP.

PMID- 7563072
TI  - Changes in conserved region 3 of Escherichia coli sigma 70 mediate ppGpp
      dependent functions in vivo.
AB  - In Escherichia coli, deletion of relA and spoT results in an inability to
      synthesize ppGpp, guanosine-3',5'-bis(pyrophosphate), and a loss in the ability
      to grow on amino acid-free minimal media. Two spontaneous missense suppressor
      alleles, rpoD(P504L) and rpoD(S506F), able to confer complete prototrophy without
      the reappearance of ppGpp, were localized to that portion of rpoD coding for
      conserved region 3.1 of sigma 70. Characterization of these mutants revealed
      distinct physiological effects. Both mutations cause growth rate defects
      exacerbated in the presence of ppGpp and paralleled by reductions in rrnB P1-lacZ
      reporter gene expression, as if growth of these mutants is limited by rrn P1
      promoter activity. Levels of ppGpp, as a function of growth rate, are lowered by
      a constant fraction (75%) in the rpoD(P504L) strain and by a decreasing fraction
      at lower growth rates in the rpoD(S506F) strain. Comparisons of rrnB P1-lacZ
      expression at different ppGpp levels is interpreted for the rpoD(P504L) mutant as
      resulting from a hypersensitivity to ppGpp. For the rpoD(S506F) mutant there is a
      normal sensitivity to ppGpp but the action of ppGpp is functionally mimicked;
      that is, a low intrinsic rrnB P1 promoter activity is manifested even in the
      absence of ppGpp. In addition to effects on rrnB P1 promoters, the accumulation
      of the stationary phase-specific sigma factor (sigma s), which is normally ppGpp
      dependent, was assayed in the rpoD mutants and in one, rpoD(S506F), found to be
      restored in the absence of ppGpp. The behavior of these mutants thus seems
      consistent with a unitary effect of ppGpp on transcription resulting in both
      negative and positive regulation of gene expression. In addition, the cellular
      fraction of sigma 70 associated with holoenzyme appears reduced by both rpoD
      mutations as judged by comparison with wild-type and ppGpp-deficient strains.
      Interestingly, the amount of holoenzyme-associated sigma 70 was higher in the
      ppGpp-deficient than in the wild-type strain, possibly indicating that sigma 70
      core RNA polymerase interactions are decreased by ppGpp.

PMID- 7563071
TI  - Short transcripts of the ternary complex provide insight into RNA polymerase II
      elongational pausing.
AB  - Expression of the hsp70 gene of Drosophila melanogaster is controlled at the
      level of transcript elongation. In the uninduced state, hsp70 possesses an RNA
      polymerase II complex, elongationally engaged, but paused early in the
      transcription unit. In this study, we have used a powerful new selection
      amplification technique to analyze the RNA transcripts associated with such
      "paused polymerases" under non-heat shock and heat shock-induced conditions. They
      reveal a region of pausing on the uninduced gene in vivo spanning from +21 to
      +35. This region is interrupted by an area of low polymerase density, centered at
      about +26. Upon induction, an accumulation of short transcripts, similar in size
      to those associated with the paused complex, was seen. Models for polymerase
      pausing and release are discussed in light of these data. The increased
      sensitivity of our new technique also allowed us to investigate ternary complexes
      associated with genes with much lower levels of engaged RNA polymerase. These
      included two of the small heat shock genes (hsp26 and hsp27) and two metabolic
      genes (Gapdh-1 and Gapdh-2), where paused polymerases were thought to be present,
      plus two other genes (Mtn and yp1), where polymerase pausing has not been
      detected in the past. In both of the small heat shock genes, we found evidence of
      previously unknown sites of transcriptional termination, residing immediately
      upstream of the regions of polymerase pausing.

PMID- 7563073
TI  - Characteristics of UV-induced mutation spectra in human XP-D/ERCC2 gene-mutated
      xeroderma pigmentosum and trichothiodystrophy cells.
AB  - To study the relationships between mutagenesis and carcinogenesis, we compared
      the mutations and their frequency induced by ultraviolet irradiation at 254 nm
      (UV-C) in XP-D (GM-08207B/XP6BE), TTD/XP-D (TTD1VI-LAS-KMT11) and wild-type (MRC
      5V1) human cells. XP-D and TTD/XP-D cells, mutated in the same XP-D/ERCC2 gene,
      are deficient in nucleotide excision repair. Whereas XP-D patients develop early
      skin tumors, TTD patients do not exhibit abnormal levels of cancers. After
      verification of UV hypersensitivity and DNA repair defect of the immortalized
      cell lines XP-D and TTD compared with a wild-type cell line, UV-induced
      mutagenesis was studied with a new shuttle vector pR2, carrying the target lacZ'
      gene. The UV-mutation frequencies in XP-D and TTD cells were similar and
      significantly increased compared with normal cells. Sequence analysis of 312
      independent mutant plasmids revealed that more rearrangements were induced in TTD
      cells (16%) than in XP-D (5%) and normal cells (1%), while XP-D cells exhibited a
      twofold higher rate of tandem mutations compared with TTD and normal cells. In
      the three cell lines, a predominance of G:C to A:T transitions was found,
      especially in chiefly on the cytosine at 5'-TC-3' sites. The types of UV-induced
      point mutations in TTD cells were, however, more similar to those in normal cells
      than those found in XP-D cells. XP-D mutations were preferentially located in 5'
      TCPur-3' sites, while mutations in normal and TTD cells were mostly at 5'-TCC-3'
      sites. Analysis of mutation spectra revealed differences in the location of the
      mutational hotspots between the three lines. Although the mutation frequency of
      the UV-irradiated pR2 vector is much higher in TTD and XP-D cells than in normal
      cells, the mutation spectrum is closer between TTD and normal cells as compared
      with XP-D cells. These dissimilarities could contribute to an explanation of some
      of the differences between the two syndromes.

PMID- 7563074
TI  - Formation of stable and functional HIV-1 nucleoprotein complexes in vitro.
AB  - HIV genomic RNA resides within the nucleocapsid, in the interior of the virus,
      which serves to protect the RNA against nuclease degradation and to promote its
      reverse transcription. To investigate the role of nucleocapsid protein (NCp7) in
      the stability and replication of genomic RNA within the nucleocapsid, we used
      NCp7, reverse transcriptase (RT) and RNAs representing the 5' and 3' regions of
      the genome to reconstitute functional HIV-1 nucleocapsids. The nucleoprotein
      complexes generated in vitro were found to be stable, which, according to
      biochemical and genetic data, probably results from the tight binding of NCp7
      molecules to the RNA and strong NCp7/NCp7 interactions. The nucleoprotein
      complexes efficiently protected viral RNA against RNase degradation and, at the
      same time, promoted viral DNA synthesis by RT. DNA strand transfer from the 5' to
      the 3' RNA template was very efficient in nucleoprotein complexes formed in the
      presence of both RNAs, but not when the RNAs were in separate complexes. These
      results indicate that the in vitro reconstituted HIV-1 nucleoprotein complexes
      function like virion nucleocapsids and thus provide a way to study at the
      molecular level this viral substructure and the synthesis of proviral DNA, and to
      search for new anti-HIV agents.

PMID- 7563075
TI  - Regions of 23 S ribosomal RNA proximal to transfer RNA bound at the P and E
      sites.
AB  - tRNAPhe transcribed in a T7 RNA polymerase system has been modified in such a way
      that 4-thiouridines have randomly replaced unmodified uridines. These 4
      thiouridines serve as sites for conjugation of the cleavage reagent 5
      iodoacetamido-1,10-phenanthroline (IOP). 1,10-Phenantholine, when complexed with
      Cu2+ in a reducing environment, causes hydrolysis of nearby nucleic acids. We
      show here that tRNA-phenanthroline (tRNA-OP) conjugates, when bound in situ to
      the P- and E-sites of 70 S ribosomes, cause cleavage, mainly in domains I, III
      and V of 23 S ribosomal RNA (rRNA). The cleavage sites in domain V predominantly
      occur very close to or in the peptidyl-transferase region. The regions of domain
      I and III that are cleaved are apparently folded in the 50 S ribosomal subunit so
      as to be proximal to the peptidyl-transferase center. Most of the cleavage events
      occur whether the tRNA-OP conjugate is bound to ribosomes alone, or yeast tRNA is
      also present in the P/P hybrid state. Cleavages that occur only in the absence of
      yeast tRNA are limited to the 1100 region of domain II, and the 2800 region of
      domain VI. Cleavages that occur only in the presence of yeast occur in the 2170
      region of domain V. The regions of 23 S rRNA in which tRNA-OP induced cleavage
      occur complement those sites shown by chemical protection and cross-liking to be
      in a close proximity to the tRNA. However, the cleavage approach allows a more
      versatile and expanded view of the near neighborhood of rRNA surrounding the
      tRNA. These results provide considerable information which will allow a more
      detailed modeling of the tertiary structure of the 50 S ribosomal subunit.

PMID- 7563076
TI  - Dissecting and analyzing the secondary structure domains of group I introns
      through the use of chimeric intron constructs.
AB  - The mitochondrial genes of the yeast Saccharomyces cerevisiae are often
      interrupted by introns defined as either group I or group II. Some of the introns
      contained within the precursor RNAs of these genes will self splice in vitro. The
      fourth introns of apocytochrome b (bi4) and cytochrome oxidase (ai4) are group I
      introns that do not self splice in vitro, even though they can fold into the same
      RNA secondary structures that are characteristic of the self-splicing introns.
      They require an intron-encoded maturase protein and a nuclear-encoded protein (a
      tRNALeu synthetase) for splicing in vivo. We have divided these introns into
      several sequence or structural elements and assayed them individually for their
      ability to support self-splicing activity. This was done by replacing the
      equivalent elements from the self-splicing intron from Tetrahymena thermophila
      with the mitochondrial elements. These intron chimeras show that peripheral
      sequences and the elements that define the splice sites are adequate for self
      splicing activity but that the central portions containing the catalytic cores of
      ai4 and bi4 are deficient; these cores are the likely targets of the splicing
      proteins. In addition, the catalytic activity of the Tetrahymena intron is
      remarkably resistant to the structural alterations that we have introduced; this
      suggests that this technique will be of general utility for studying the
      structural and functional relationships of elements contained within different
      RNAs.

PMID- 7563077
TI  - The modular character of a DNA junction-resolving enzyme: a zinc-binding motif in
      bacteriophage T4 endonuclease VII.
AB  - Bacteriophage T4 endonuclease VII is one of a class of structure-selective
      enzymes that resolve helical branchpoints in DNA molecules. The sequence of this
      protein suggests a modular organisation. We have expressed a synthetic gene
      encoding endonuclease VII, which has been used in a directed mutagenesis
      exercise, with the aim of understanding the role of different sections of the
      protein sequence. Towards the N-terminal end of the protein lies a section of
      polypeptide in which four cysteine residues distributed in a CxxC--CxxC pattern
      co-ordinate one atom of zinc. The N-terminal section composed of amino acid
      residues 1 to 65 isolated from the remaining C-terminal section also binds one
      mole of zinc, suggesting that this region folds autonomously. Mutation shows that
      the outer cysteine residues are essential for zinc binding, while the inner
      cysteine residues are partially degenerate in that either one of the two (but not
      both) can be replaced while retaining some zinc. The activity as a junction
      resolving enzyme correlated qualitatively with the presence of the zinc. In the C
      terminal part of the protein lies a section that is 48% identical with a sequence
      found in the DNA repair protein T4 endonuclease V. We can replace the section of
      T4 endonuclease VII with the corresponding sequence from T4 endonuclease V with
      no change in the pattern of cleavage on four-way junctions. The evidence supports
      a modular construction for T4 endonuclease VII.

PMID- 7563078
TI  - Structural changes in actin-tropomyosin during muscle regulation: computer
      modelling of low-angle X-ray diffraction data.
AB  - The crystal structure of G-actin monomer has been used together with tropomyosin
      in a filament model to explain the low-angle X-ray diffraction data from relaxed
      and activated actin filaments. The four-subdomain actin monomer can be
      approximated quite well by a four-sphere unit. Orienting this unit and
      tropomyosin into a filament by searching for the best fit between the computed
      Fourier transform and the observed vertebrate skeletal muscle low-angle actin
      layer-lines from muscles at non-overlap sarcomere lengths produced models for the
      structural changes within the thin filaments (actin plus tropomyosin) between the
      resting state and the active states, which occur as a result of calcium
      activation and independent of myosin interaction with actin. The models are very
      sensitive to changes in the positions of the centres of mass of the subdomains,
      but not to the exact shape of the objects used to represent them (e.g. spheres,
      ellipsoids etc.), as long as the volume is fixed, at the resolution here
      considered. It is concluded that, even with a four-subdomain structure for the
      actin molecules, the observed low-angle X-ray diffraction patterns cannot be
      explained without a substantial azimuthal swing of the tropomyosin strands when
      resting filaments are calcium-activated. The direction of this swing upon calcium
      activation is away from a position close to the proposed major binding site of
      the myosin head on actin; a result consistent with the original "steric blocking
      model" of thin filament-based regulation in which the tropomyosin position on
      actin is crucial for regulation of the myosin crossbridge cycle on actin.
      Tropomyosin sterically hindering myosin attachment in the "off" state remains a
      possibility. However, even in the "on" state, the tropomyosin position is close
      enough to the myosin-binding site to have an effect, where it could regulate the
      transition of the head from a weak to a strong state. In addition to this
      tropomyosin movement there are small, but plausible, actin subdomain movements. A
      tropomyosin shift on its own will not explain the data. Allowance for possible
      movement of actin subdomain 2 along with the tropomyosin shift still does not
      explain the data. An additional small movement of subdomain 1; the main myosin
      binding subdomain, is postulated.

PMID- 7563079
TI  - Self-association of beta-amyloid peptide (1-40) in solution and binding to lipid
      membranes.
AB  - The beta-amyloid peptide (beta AP), a 39 to 43 residue peptide, is the major
      component of Alzheimer plaques. Using circular dichroism spectroscopy, titration
      calorimetry, and analytical ultracentrifugation we have analyzed the self
      association of beta AP(1-40) in aqueous solution and the binding of beta AP(1-40)
      to negatively charged lipid vesicles. The CD spectra of both aggregation and
      membrane binding are characterized by an isodichroic point at 212 nm, indicating
      a simple two-state equilibrium for both cases. In aqueous solution beta AP(1-40)
      exhibits a reversible, concentration-dependent random coil<-->beta-structure
      transition which can be described by a cooperative aggregation model with an
      association constant of s = 1.05 x 10(4)M-1 and a nucleation parameter of sigma =
      0.012. A similar conformational change is observed upon addition of lipid. At a
      given peptide concentration, the addition of negatively charged, small
      unilamellar vesicles also induces a conformational change from a random coil
      conformation to a conformation with 40 to 60% beta-structure. The binding
      isotherm can be measured with high sensitivity titration calorimetry. It is
      approximately linear in the initial binding phase and exhibits an apparent
      saturation behaviour. The apparent binding constant decreases with concentration
      from Kapp approximately 2100 M-1 at low concentration to 700 M-1 at the highest
      concentration measured. Peptide penetration into the lipid membrane and peptide
      aggregation at the membrane surface are proposed as possible mechanisms to
      explain the lipid-induced random coil<-->beta-structure transition.

PMID- 7563080
TI  - Crystallographic structure of a PLP-dependent ornithine decarboxylase from
      Lactobacillus 30a to 3.0 A resolution.
AB  - Ornithine decarboxylase from Lactobacillus 30a (L30a OrnDC) is representative of
      the large, pyridoxal-5'-phosphate-dependent decarboxylases that act on lysine,
      arginine or ornithine. The crystal structure of the L30a OrnDC has been solved to
      3.0 A resolution using MIR phases in combination with density modification (space
      group P6; a = 195.6 A, c = 97.6 A; dimer of 1460 amino acid residues/asymmetric
      unit; VM = 3.26 A3/Da). The refined crystallographic R-value was 0.219 (Rfree =
      0.268) using 2-fold restraints with a 4 sigma cutoff and 8.0 to 3.0 A resolution
      data. Six dimers related by C6 symmetry compose the enzymatically active
      dodecamer (approximately 10(6) Da). Each monomer of L30a OrnDC can be described
      in terms of five sequential folding domains. The amino-terminal domain, residues
      1 to 107, consists of a five-stranded beta-sheet termed the "wing" domain. Two
      wing domains of each dimer project inward towards the center of the dodecamer and
      contribute to dodecamer stabilization. The "linker" domain, residues 108 to 160,
      consists of short alpha-helices separated by a loop that fills in the PLP pocket.
      The third domain, residues 161 to 413, is an alpha/beta domain containing a seven
      stranded beta-sheet that resembles the PLP-binding domain of the aspartate
      aminotransferases. The fourth domain, residues 414 to 569, resembles the "small"
      domain of the aspartate aminotransferases, but is significantly larger due to
      insertions. The remaining carboxy-terminal domain, residues 570 to 730, is
      organized into multiple antiparallel loops and seven alpha-helices that help form
      a deep channel leading to the PLP-binding site.

PMID- 7563081
TI  - Thrombin-bound structures of designed analogs of human fibrinopeptide A
      determined by quantitative transferred NOE spectroscopy: a new structural basis
      for thrombin specificity.
AB  - The mutation of Gly12 to Val12 in the A alpha chains of human fibrinogen Rouen is
      associated with a delayed proteolytic release of fibrinopeptide A (FpA or A alpha
      1 to 16 of fibrinogen) by thrombin, leading to a bleeding disorder. Analogs of
      FpA and FpA Rouen have been designed that include a Pro15 to replace Val15 in
      natural FpA and to mimic the frequent occurrences of a proline residue at
      equivalent positions of other protein substrates of thrombin. The Pro15 analogs
      of FpA and FpA Rouen bind specifically to the active site of thrombin as shown by
      thrombin-induced differential line broadening and transferred nuclear Overhauser
      effects (transferred NOEs). Pro15 is well tolerated by the thrombin-bound
      structures of both FpA and FpA Rouen in solution, resulting in enhanced
      conformational stabilities of the thrombin-FpA complexes. The Val12 mutation in
      FpA Rouen causes backbone conformational changes in residues Val12 and Gly13
      accompanied by an expansion of the hydrophobic cluster of FpA to accommodate the
      bulky side-chain of Val12. The single turn of helical structure between residues
      Asp7 and Glu11 is stabilized by hydrogen bonds from the side-chain carboxylate of
      Asp7 to the exposed backbone NH groups of Ala10 and/or Leu9 (N-capping), and by
      hydrogen bonds between the exposed backbone carbonyl groups of residues Phe8 and
      Leu9, and the backbone NH groups of Gly12/Val12 and Gly13 (C-capping). The bound
      structure of FpA Rouen may be further stabilized by a non-polar (i,i + 4)
      interaction between the aromatic side-chain of Phe8 and the aliphatic side-chain
      of Val12. Despite these optimized intrapeptide interactions, the thrombin-peptide
      interactions are highly dynamic as indicated by the fast rate of dissociation
      (koff > 100 s-1) of the peptide ligands from the thrombin complexes. Sequence
      comparison between mammalian fibrinopeptides A and B suggests that the
      specificity of thrombin is dictated by a four-residue consensus motif, Phe(P4)
      Xxx(P3)-Pro(P2)-Arg(P1) or FXPR, when Xxx at P3 can be a charged or a neutral
      polar residue capable of specific interactions with residues near the active site
      of thrombin.

PMID- 7563083
TI  - Recognizing native folds by the arrangement of hydrophobic and polar residues.
AB  - Central to the ab initio protein folding problem is the development of an energy
      function for which the correct native structure has a lower energy than all other
      conformations. Existing potentials of mean force typically rely extensively on
      database-derived contact frequencies or knowledge of three-dimensional structural
      information in order to be successful in the problem of recognizing the native
      fold for a given sequence from a set of decoy backbone conformations. Is the
      detailed statistical information or sophisticated analysis used by these
      knowledge-based potentials needed to achieve the observed degree of success in
      fold recognition? Here we introduce a novel pairwise energy function that
      enumerates contacts between hydrophobic residues while weighting their sum by the
      total number of residues surrounding these hydrophobic residues. Thus it
      effectively selects compact folds with the desired structural feature of a
      buried, intact core. This approach represents an advance over using pairwise
      terms whose energies of interaction that are independent of the position in the
      protein and greatly improves the discrimination capability of an energy function.
      Our results show that 85% of a set of 195 representative native folds were
      recognized correctly. The 29 exceptions were lipophilic proteins, small proteins
      with prosthetic groups or disulfide bonds, and oligomeric proteins. Overall, our
      method separates the native fold from incorrect folds by a larger margin
      (measured in standard deviation units) than has been previously demonstrated by
      more sophisticated methods. The arrangement of hydrophobic and polar residues
      alone as evaluated by our novel scoring scheme, is unexpectedly effective at
      recognizing native folds in general. It is surprising that a simple binary
      pattern of hydrophobic and polar residues apparently selects a give unique fold
      topology.

PMID- 7563082
TI  - Acid and thermal denaturation of barnase investigated by molecular dynamics
      simulations.
AB  - The transition in barnase from the native state to a partially unfolded
      conformation has been studied by molecular dynamics simulations with explicit
      water molecules at 360 K and low pH(450 ps), and at 600 K and neutral pH (three
      simulations of 120, 250 and 200 ps each). The use of several simulations provides
      evidence that the results are not sensitive to initial conditions. To mimic low
      pH conditions, the acidic sidechains in barnase were neutralized and the two
      histidine residues were doubly protonated. Runs at 300 K showed that the solvated
      structures at low pH (300 ps) and neutral pH (310 ps) are very similar. The main
      structural differences involved the acidic residues, histidine residues, and the
      beta-turn connecting strands 4 and 5. When the temperature is raised to 360 K at
      low pH and to 600 K at neutral pH the barnase molecule begins to unfold. The
      molecule rapidly expands (Rg changes from 13.9 A to 15.3 A in 450 ps at 360 K and
      from 13.7 A to between 15.1 and 15.5 A in 120 ps at 600 K). However, the
      expansion is not uniform. In all the simulations, the chain termini, loops and
      the N-terminal parts of the main alpha-helix (helix 1) show a continuous and
      progressive unfolding. An essential step in the denaturation process is that the
      major alpha-helix (helix 1) separates from the beta-sheet; this is coupled to the
      exposure of the principal hydrophobic core, many of whose non-polar side chains
      become solvated by hydrogen-bonded water molecules. The barnase-water interaction
      energy improves during unfolding at the expense of the barnase self-energy. The
      deterioration of the intramolecular van der Waals energy suggests that the
      rupture of the tight packing during the initial unfolding phase contributes to
      the energy barrier of the denaturation process. The mutationally well-analyzed
      Asp8-Arg110-Asp12 double salt-bridge on the barnase surface is found to be
      marginally stable in the folded form in the simulations. A Poisson-Boltzmann
      calculation indicates that the salt-bridge is unstable; this is probably due to
      an overestimate of the solvation energy. A detailed analysis of the main
      hydrophobic core reveals that increase in solvent-accessible surface area and
      penetration of water molecules are simultaneous in the high-temperature
      simulation; at lower temperatures there is significant cavity formation and the
      entrance of the water molecules is somewhat delayed. The cavities occur in the
      neighborhood of the hydrophobic sidechains; the region formed by the sidechains
      of Val10, Leu14, Leu20, Tyr24, Ala74, Ile76 and Tyr90 is involved. The loosening
      of the core packing is coupled to an increase in the number of dihedral
      transitions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7563084
TI  - GABA receptor minigene rescues insecticide resistance phenotypes in Drosophila.
AB  - A single point mutation within the GABA receptor gene Resistance to dieldrin
      (Rdl) confers a high level of resistance to cyclodiene insecticides in a wide
      range of insects. Previous studies have shown partial rescue of the susceptible
      phenotype via germline transformation of a 36 kb cosmid coding (or all four
      alternative Rdl splice forms. Here, we describe the construction of two Rdl
      promoter/cDNA minigenes, each coding for one of the splice forms alone. Single
      splice forms rescued both the insecticide susceptible and resistant phenotypes
      associated with the locus as effectively as the complete cosmid. The minigenes
      also rescue the lethality associated with homozygous re-arrangements disrupting
      the Rdl gene, and the level of rescue observed is not increased by the addition
      of more than one splice form. This demonstrates that only a single Rdl splice
      form is necessary both to confer insecticide sensitivity and also to rescue
      lethality. Methods by which phenotype rescue could be enhanced and the potential
      advantages of using Rdl as a selectable marker are discussed.

PMID- 7563085
TI  - Single base-pair precision and structural rigidity in a small IHF-induced DNA
      loop.
AB  - The prokaryotic integration host factor (IHF) is a DNA-bending protein that binds
      to specific DNA sites as a heterodimer. Genetic and mutational analyses have
      previously identified asymmetric protein-DNA contacts by the individual subunits.
      By exploiting the unique sequence and positional context of one IHF binding site,
      H' in Lambda attachment sites (att sites), we have identified a symmetry element
      of binding and have localized the functional bend center to the center of this
      symmetry. A shift of the H' bend center by a single base-pair to the right or to
      the left within the very tight loop formed with Lambda integrase (Int) and IHF in
      att-site "intasomes" severely reduces recombination. This suggests that a
      precise, but wrongly positioned, DNA bend within a loop of constant length
      negatively influences the juxtaposition or "phasing" of the core-type and arm
      type Int binding sites by differentially affecting the length of each leg of the
      loop. Furthermore, ten base-pair insertions within this loop that should not
      interfere with correct helical phasing are sensed in a position-dependent manner.
      Distal insertions abolish recombination, whereas proximal or double insertions
      (in both legs of the loop) are well tolerated.

PMID- 7563086
TI  - The amino terminal domain of HIV-1 Rev is required for discrimination of the RRE
      from nonspecific RNA.
AB  - The ability of HIV-1 Rev to successfully discriminate between specific Rev
      responsive elements (RRE) and nonspecific binding sites in the presence of excess
      nonspecific RNA was examined using filter binding, gel shift, and gel filtration
      techniques, using purified M4 Rev mutant protein and endoproteinase Lys-C cleaved
      wild-type Rev. The M4 Rev displayed a slightly reduced binding affinity to the
      RRE, as well as a tenfold decrease in its ability to discriminate the RRE from
      non-specific RNA compared to the wild-type Rev. Gel shift and gel filtration
      chromotography data also showed decreased ability of the mutant to multimerize in
      the absence or presence of the RRE. The Lys-C cleaved Rev, which lacks the amino
      terminal 20 amino acids of the protein, displayed less ability to discriminate
      the RRE from nonspecific RNA compared to either the wild-type or the M4 mutant
      Rev and appeared unable to form protein-protein interactions, yet still bound
      sense and antisense RNA species with high affinity (Kd was in the nanomolar
      concentration range). A 40 amino acid peptide containing the arginine-rich RRE
      binding domain of Rev was also observed to interact with both the RRE and
      antisense RNA fragments with a binding constant of about 1 x 10(-9) M. However,
      the peptide displayed almost no ability to discriminate between the RRE and a
      comparably sized antisense RRE. The loss in ability to discriminate correct from
      incorrect binding sites correlates with overall decreases in the alpha-helical
      character of the protein and perturbations within the amino terminus. The amino
      terminus of Rev is likely to maintain the conformational integrity of the
      arginine rich RRE binding domain which is required for specific RNA binding site
      discrimination or stabilization of specific Rev-RRE interactions.

PMID- 7563087
TI  - Heterogeneity of E. coli RNA polymerase revealed by high pressure.
AB  - The activity and subunit association of Escherichia coli RNA polymerase has been
      investigated by high pressure techniques (up to 2000 atm). The extent of subunit
      dissociation in the presence and absence of DNA was monitored by carrying out
      electrophoresis directly at elevated pressure. The degree of inactivation brought
      about by high pressure was determined by measuring the enzyme activity following
      decompression. The loss of activity if the enzyme molecules are not actively
      involved in transcription is correlated with the extent of association of the
      polymerase subunits. At any particular pressure only a fraction of polymerase
      molecules becomes inactivated; the remaining fraction retains its original
      activity characteristics. If the enzyme molecules are actively involved in
      transcription when the high pressure is applied, the RNA synthesis can be
      completely halted, but the elongation activity is fully recovered on
      decompression. The experimental results are consistent with the existence of a
      broad distribution of protein conformers that are differentially sensitive to the
      level of pressure. RNA polymerase molecules that display similar catalytic
      properties have large differences in their free energy of subunit association in
      the absence of substrates.

PMID- 7563088
TI  - Evidence for coupling of folding and function in trp repressor: physical
      characterization of the superrepressor mutant AV77.
AB  - The fine-control of gene expression in the trp repressor system is achieved
      through the thermodynamic linkage of multiple equilibria involving the trp
      repressor protein (TR), tryptophan (L-Trp) and DNA. We have undertaken studies of
      superrepressor mutants of TR as a means of dissecting the coupled equilibria that
      contribute to repressor function. Unlike all the other tested super-repressors
      that exhibit differences from wild-type TR DNA binding affinity or stoichiometry,
      the AV77 superrepressor (an alanine to valine substitution at position 77:
      AV77TR) has been indistinguishable from TR in vitro. The present studies using a
      variety of biophysical measurements comparing TR and AV77TR provide strong
      evidence that the helix-turn-helix (HTH) region of apoTR exists in a partially
      folded conformation. Far UV CD spectra of the two proteins reveal a 10% increase
      in helical content for the apoAV77TR compared to apoTR. Moreover, urea
      denaturation studies demonstrate that apoAV77TR is more stable to denaturation
      than apoTR. ApoTR binds large amounts of 1,8-ANS, a hydrophobic fluorescence
      probe used to detect protein folding intermediates, with high affinity, where
      apoAV77TR exhibits only marginal binding of this ligand. While the tryptophan
      affinities of the two proteins as measured by titration calorimetry are quite
      similar, the thermodynamic signatures are distinct, with a much reduced
      unfavorable entropic contribution for AV77TR. Finally, the allosteric effect of L
      Trp on oligomerization is abolished by the AV77 mutation. Taken together these
      data support previous calorimetric studies implicating coupling of folding and L
      Trp binding for TR. Moreover, they are consistent with NMR observations
      indicating partial disorder in the HTH region of apoTR. Based upon the distinct
      biophysical properties of TR and AV77TR, we propose a model in which folding of
      the HTH region accompanies ligand binding in TR. In this model distinct protein
      protein interactions of the apo- and holoTR link this conformational change to
      apparent operator affinities, thereby modulating TR function in vivo.

PMID- 7563089
TI  - Stabilised secondary structure at a ribosomal binding site enhances translational
      repression in E. coli.
AB  - The expression of the gene encoding Escherichia coli threonyl-tRNA synthetase is
      negatively autoregulated at the translational level. The negative feedback is due
      to the binding of the synthetase to an operator site on its own mRNA located
      upstream of the initiation codon. The present work describes the characterisation
      of operator mutants that have the rare property of enhancing repression. These
      mutations cause (1) a low basal level of expression, (2) a temperature-dependent
      expression, and (3) an increased capacity of the synthetase to repress its own
      expression at low temperature. Surprisingly, this enhancement of repression is
      not explained by an increase of affinity of the mutant operators for the enzyme
      but by the formation, at low temperature, of a few supplementary base-pairs
      between the ribosomal binding site and a normally single-stranded domain of the
      operator. Although this additional base-pairing only slightly inhibits ribosome
      binding in the absence of repressor, simple thermodynamic considerations indicate
      that this is sufficient to increase repression. This increase is explained by the
      competition between the ribosome and repressor for overlapping regions of the
      mRNA. When the ribosomal binding site is base-paired, the ribosome cannot bind
      while the repressor can, giving the repressor the advantage in the competition.
      Thus, the existence of an open versus base-paired equilibrium in a ribosomal
      binding site of a translational operator amplifies the magnitude of control. This
      molecular amplification device might be an essential component of translational
      control considering the low free repressor/ribosome ratio of the low affinity of
      translational repressors for their target operators.

PMID- 7563090
TI  - Plus-strand DNA synthesis of the yeast retrotransposon Ty1 is initiated at two
      sites, PPT1 next to the 3' LTR and PPT2 within the pol gene. PPT1 is sufficient
      for Ty1 transposition.
AB  - Long terminal repeat elements and retroviruses require primers for initiation of
      minus and plus-strand DNA synthesis by reverse transcriptase. Here we demonstrate
      genetically that plus-strand DNA synthesis of the yeast Ty1 element is initiated
      at two sites located at the 5' boundary of the 3' long terminal repeat (PPT1) and
      near the middle of the pol gene in the integrase coding sequence (PPT2). A
      consequence of the presence of two PPTs is that Ty1 plus-strand DNA exists as
      segments at some time during replication. Three fragments have been identified:
      the plus-strand strong-stop DNA initiated at PPT1, a downstream fragment
      initiated at PPT2 and an upstream fragment spanning the 5'-terminal part of Ty1
      and a portion of the TyB gene. Characterization of the 3' ends of the plus-strand
      DNA fragments reveals (1) that the upstream fragment is elongated beyond PPT2
      creating a plus-strand overlap and (2) that the majority of plus-strand strong
      stop DNA fragments bear a copy of the minus-strand primer binding site in
      agreement with the accepted model of retroviral genomic RNA reverse
      transcription. The two polypurine tracts, PPT1 and PPT2, have an identical
      sequence GGGTGGTA. Mutations replacing purines by pyrimidines in this sequence
      significantly diminish or abolish initiation of plus-strand synthesis. Ty1
      elements bearing a mutated PPT2 sequence are not defective for transposition
      whereas mutations in PPT1 abolish transposition.

PMID- 7563091
TI  - Effect of folding on the export of ribose-binding protein studied with the
      genetically isolated suppressors for the signal sequence mutation.
AB  - Ribose-binding protein (RBP) has a bilobate structure and functions in the
      periplasm of Escherichia coli. Mutations that affect the folding of RBP were
      isolated as intragenic suppressors for the export-defective signal sequence
      mutation. Of 13 different mutational changes found in the mature region, 12 were
      located in the several peptides forming the N-domain, and one in the C-domain.
      Translocation kinetics of mutant proteins were analyzed by pulse-labeling and
      chase experiments, showing the recovery of precursor processing in the range of
      42 to 70%. Folding properties of seven mutant RBPs purified were investigated in
      vitro by means of tyrosine fluorescence. The stability of the mutant proteins,
      estimated by equilibrium analysis in the presence of denaturant, were reduced by
      2.1 to 5.1 kcal/mol of changes in free energy of unfolding. All the mutant
      proteins showed retardation in folding rate by 4.4 to 63-fold compared to wild
      type while unfolding was little affected. The only exception was the L129Q that
      has a change in the C-domain resulting in unstability due to faster unfolding.
      Our approach took advantage of an involvement of the folding process in protein
      export, which was genetically employed to dissect the folding pathway of RBP. As
      a result, amino acid residues that are specifically involved in the folding
      pathway of RBP were identified. Most of them are concentrated in one of the
      subdomains, suggesting that the folding event in the N-domain of RBP is crucial
      in the rate-determining step.

PMID- 7563092
TI  - The structure of the human immunodeficiency virus type-1 TAR RNA reveals
      principles of RNA recognition by Tat protein.
AB  - The human immunodeficiency virus type-1 (HIV-1) Tat protein stimulates
      transcriptional elongation. Tat is introduced to the transcription machinery by
      binding to the transactivation response region (TAR) RNA stem-loop encoded by the
      5' leader sequence found on all HIV-1 mRNAs. We have used multidimensional
      heteronuclear NMR to determine the structure of the TAR RNA in the presence of
      the ADP-1 polypeptide, a 37-mer that carries the minimal RNA recognition region
      of the Tat protein and closely mimics Tat binding specificity. In the presence of
      a variety of ligands, including ADP-1, related basic peptides and the amino acid
      derivative argininamide, the bulge region of TAR undergoes a local conformational
      rearrangement and forms a more stable structure. The structure of TAR in the
      bound form has been determined from over 1000 NMR-derived constraints. The U23
      residue at the 5' end of the bulge is positioned near G26 and A27 in the major
      groove, rather than stacked on A22 as in the free TAR. U23 and G26 are brought
      into close proximity by contacts to the guanidinium group and side-chain amide
      group of a common arginine residue. However, the interaction of this guanidinium
      group with TAR is not the only source of binding specificity. Besides NOEs to the
      arginine residue participating in the conformational change, ADP-1 shows
      additional intermolecular NOEs to TAR, suggesting that there are multiple points
      of contacts between TAR RNA and residues from the basic and core regions of Tat.
      These structural results provide important clues towards the identification of
      small molecular mass and/or peptidomimetic inhibitors of the essential Tat-TAR
      interaction.

PMID- 7563093
TI  - High-resolution structure of the catalytic domain of avian sarcoma virus
      integrase.
AB  - Retroviral integrase (IN) functions to insert retroviral DNA into the host cell
      chromosome in a highly coordinated manner. IN catalyzes two biochemically
      separable reactions: processing of the viral DNA ends and joining of these ends
      to the host DNA. Previous studies suggested that these two reactions are
      chemically similar and are carried out by a single active site that is
      characterized by a highly conserved constellation of carboxylate residues, the
      D,D(35)E motif. We report here the crystal structure of the isolated catalytic
      domain of avian sarcoma virus (ASV) IN, solved using multiwavelength anomalous
      diffraction data for a selenomethionine derivative and refined at 1.7 A
      resolution. The protein is a crystallographic dimer with each monomer featuring a
      five-stranded mixed beta-sheet region surrounded by five alpha-helices. Based on
      the general fold and the arrangement of catalytic carboxylate residues, it is
      apparent that ASV IN is a member of a superfamily of proteins that also includes
      two types of nucleases, RuvC and RNase H. The general fold and the dimer
      interface are similar to those of the analogous domain of HIV-1 IN, whose crystal
      structure has been determined at 2.5 A resolution. However, the ASV IN structure
      is more complete in that all three critical carboxylic acids, Asp64, Asp121 and
      Glu157, are ordered. The ordered active site and the considerably higher
      resolution of the present structure are all important to an understanding of the
      mechanism of retroviral DNA integration, as well as for designing antiviral
      agents that may be effective against HIV.

PMID- 7563095
TI  - 6-Pyruvoyl tetrahydropterin synthase, an enzyme with a novel type of active site
      involving both zinc binding and an intersubunit catalytic triad motif; site
      directed mutagenesis of the proposed active center, characterization of the metal
      binding site and modelling of substrate binding.
AB  - 6-Pyruvoyl tetrahydropterin synthase (PTPS) is an enzyme involved in
      tetrahydrobiopterin biosynthesis, the cofactor for several aromatic amino acid
      monooxygenases and the nitric oxide synthases. The crystal structure of PTPS was
      recently solved and showed a homohexameric enzyme composed of a dimer of trimers.
      A transition metal binding site formed by the three histidine residues 23, 48 and
      50 was found in each subunit. We showed by metal analysis and reconstitution of
      apo-PTPS that Zn(II) was the bound transition metal and responsible for the
      enzymatic activity. Site-directed mutagenesis of each of these three histidine
      residues resulted in a complete loss of metal binding and enzymatic activity. The
      three residues, Cys42, His89 and Glu133, located close to the metal binding site,
      were previously postulated to be involved in the catalytic reaction. We altered
      these residues and found a complete loss of enzymatic activity for the mutant
      C42A. The two mutants, H89N and E133Q, showed 4.3% and 1.3% enzymatic activity,
      respectively, but had similar KM values for the substrate as compared to wild
      type PTPS. Based on these results we propose a model of the substrate fitted into
      the active site and we described a novel intersubunit catalytic triad motif
      composed of the amino acid residues Cys42, His89 and Asp88. Different from most
      other catalytic triads that catalyse the hydrolysis of an amide or ester bond,
      the catalytic triad in the active site of PTPS seems to be involved in the
      deprotonation of the substrate's side-chain carbons. Our model also proposes
      Zn(II) as the coordination site for the two substrate side-chain hydroxy groups
      as well as the involvement of Glu133 as putative stereospecific proton server.

PMID- 7563094
TI  - The C-terminal portion of BM-40 (SPARC/osteonectin) is an autonomously folding
      and crystallisable domain that binds calcium and collagen IV.
AB  - The extracellular glycoprotein BM-40 consists of three domains, an acidic domain
      I, a follistatin (FS)-like domain II and a calcium-binding EC domain with an EF
      hand related motif. BM-40 and several other related proteins (QR1, SC1/hevin,
      testican and tsc-36/FRP) are members of a novel modular protein family that share
      the FS domain followed by an EC domain. We have expressed this pair of FS and EC
      domains (mutant delta I) and the calcium-binding EC domain alone (mutant delta I,
      II) of human BM-40 as recombinant proteins in human 293 cells. Circular dichroism
      demonstrated that both mutants were obtained as folded proteins with a distinct
      three-dimensional conformation. In addition, mutant delta I, II could be readily
      crystallized and diffraction patterns with a resolution limit of 2.4 A resolution
      were obtained. Calcium binding to this fragment was ten times weaker (Kd = 0.8
      microM) than for the wild-type protein. Identical reversible increases in alpha
      helicity upon calcium binding were observed for the 150-residue long mutant delta
      I, II and for BM-40 (286 residues). A 26-residue synthetic peptide corresponding
      to the EF-hand related motif exhibited much weaker calcium binding. The apparent
      dissociation constant decreased with increasing peptide concentration (from Kd
      2.4 mM at 1 microM, to Kd 0.3 mM at 100 microM peptide concentration) and calcium
      binding was accompanied by dimerization of the peptide. This suggests that for
      strong calcium binding the EF-hand related motif has to be embedded into a larger
      protein domain that can form an autonomously folding protein module. The EC
      domain was also shown by surface plasmon resonance assay to be responsible for
      calcium-dependent binding to collagen IV with an affinity (Kd = 19 microM) only
      sixfold lower than that of intact human BM-40.

PMID- 7563096
TI  - Comprehensive analysis of hydrogen bonds in regulatory protein DNA-complexes: in
      search of common principles.
AB  - A systematic analysis of hydrogen bonds between regulatory proteins and their DNA
      targets is presented, based on 28 crystallographically solved complexes. All
      possible hydrogen bonds were screened and classified into different types: those
      that involve the amino acid side-chains and DNA base edges and those that involve
      the backbone atoms of the molecules. For each interaction type, all bonds were
      characterized and a statistical analysis was performed to reveal significant
      amino acid-base interdependence. The interactions between the amino acid side
      chains and DNA backbone constitute about half of the interactions, but did not
      show any amino acid-base correlation. Interactions via the protein backbone were
      also observed, predominantly with the DNA backbone. As expected, the most
      significant pairing preference was demonstrated for interactions between the
      amino acid side-chains and the DNA base edges. The statistically significant
      relationships could mostly be explained by the chemical nature of the
      participants. However, correlations that could not be trivially predicted from
      the hydrogen bonding potential of the residues were also identified, like the
      preference of lysine for guanine over adenine, or the preference of glutamic acid
      for cystosine over adenine. While Lys x G interactions were very frequent and
      spread over various families, the Glu x C interactions were found mainly in the
      basic helix-loop-helix family. Further examination of the side-chain-base edge
      contacts at the atomic level revealed a trend of the amino acids to contact the
      DNA by their donor atoms, preferably at position W2 in the major groove. In most
      cases it seems that the interactions are not guided simply by the presence of a
      required atom in a specific position in the groove, but that the identity of the
      base possessing this atom is crucial. This may have important implications in
      molecular design experiments.

PMID- 7563098
TI  - Potassium regulation during exercise and recovery in humans: implications for
      skeletal and cardiac muscle.
AB  - This review summarizes the main cellular mechanisms involved in potassium
      regulation in plasma and skeletal muscle during exercise. The effects of exercise
      induced hyperkalemia and post-exercise hypokalemia on the cardiac action
      potential are reviewed in light of recent research on Na+ and K+ channel
      activity. Specific consideration is given to K+ release from contracting skeletal
      muscle, K+ uptake by contracting skeletal muscle, K+ uptake by non-contracting
      tissues during the period of exercise, and K+ uptake by skeletal muscle
      recovering from contractile activity. The onset of exercise is associated with a
      net release of K+ from contracting skeletal muscle that results in an increase in
      plasma [K+]. Resultant decreases in intracellular [K+] and increases in
      interstitial [K+] in contracting skeletal muscle have been implicated in the
      fatigue process. The rate and magnitude of increase in plasma [K+] is dependent
      on exercise intensity, trained state of the individual, and on drugs such as beta
      adrenoceptor blockers and caffeine. During exercise, the uptake of K+ from the
      blood by non-contracting tissues may be important in preventing plasma [K+] from
      rising to excessive levels that will impair skeletal muscle and myocardial
      excitability and contractility. Cessation of exercise results in a rapid decrease
      in plasma [K+], often to 3 mEq/l or less with intense exercise, that may be
      maintained for prolonged periods. The rapid increases and decreases in plasma
      [K+] with onset and cessation of exercise, respectively, has been implicated in
      altered myocardial function and sudden cardiac death. Recent studies suggest that
      increases in catecholamines during exercise are cardioprotective to the
      arrhythmogenic effects of hyperkalemia.

PMID- 7563097
TI  - Significance of sodium pump isoforms in digitalis therapy.
AB  - Despite the long history of use of cardiac glycosides, questions persist relating
      to the very narrow range of therapeutic v toxic levels of the drug, and the
      factors, including hypokalemia, that predispose a patient to cardiac glycoside
      toxicity. The therapeutic receptor for cardiac glycosides is believed to be the
      alpha subunit of sodium pump, Na,K-ATPase. Three isoforms of this subunit are
      expressed in the heart, and the levels of cardiac sodium pump expression are
      depressed in heart failure. Which human sodium pump isoform(s) binds cardiac
      glycosides in the therapeutic range (1-2 nM for digoxin) in the failing heart has
      not been determined. Hypokalemia can potentially influence cardiac glycoside
      sensitivity at multiple levels: (1) it directly increases the affinity of cardiac
      glycosides for sodium pumps by decreasing competition with K+, (2) it decreases
      cardiac sodium pump expression which can augment or amplify the effects of
      decreased pump expression and activity due to heart failure itself and cardiac
      glycoside inhibition; (3) it decreases the expression of skeletal muscle sodium
      pumps which will influence the relative tissue and plasma distributions of
      cardiac glycosides. Establishing the therapeutic v toxic targets of cardiac
      glycosides will enable investigators to design isoform specific inhibitors that
      would potentially be specific for the therapeutic receptors and independent of
      plasma potassium levels.

PMID- 7563099
TI  - A "second window of protection" or delayed preconditioning phenomenon: future
      horizons for myocardial protection?

PMID- 7563100
TI  - The role of oxygen free radicals in preconditioning.

PMID- 7563101
TI  - Harnessing an endogenous cardioprotective mechanism: cellular sources and sites
      of action of adenosine.
AB  - Endogenous adenosine is produced by the heart during ischemia-reperfusion as a
      natural cardioprotectant. The benefits of this local protective mechanism can be
      harnessed by ischemic preconditioning and amplified by drugs such as acadesine,
      that augment extracellular adenosine levels specifically during an ischemic
      event. Classically, adenosine production by cardiomyocytes, and measured in the
      interstitial fluid, is considered the relevant source of this mediator. In
      contrast, it is proposed that there are two independent sites of adenosine
      formation in the heart--the myocytes and the endothelial cells, that are
      differentially regulated. Recent evidence implicates the vascular endothelium as
      a potentially important site of both adenosine formation and action that
      subserves the cardioprotective effects of the nucleoside. The mechanisms by which
      endogenous adenosine protects the heart from ischemia-reperfusion injury require
      clarification, and may involve different adenosine receptors (A1, A2, and A3)
      acting through various second messenger systems that contribute to the overall
      response. Additional studies are required to define the source of adenosine, the
      mechanisms by which its levels are regulated, and the effector pathways
      responsible for the myocardial protection observed.

PMID- 7563102
TI  - Combination therapy with probucol prevents adriamycin-induced cardiomyopathy.
AB  - Adriamycin (doxorubicin) is a broad spectrum anti-tumor antibiotic used to treat
      cancer patients. However, the potential usefulness of this drug is currently
      limited by the development of a dose-dependent cardiomyopathic process
      terminating in severe heart failure. Although several mechanisms have been
      suggested to explain the pathogenesis of adriamycin-induced cardiomyopathy, free
      radical induced oxidative stress appears to play an important role. A concise
      description of adriamycin-induced cardiomyopathy is provided. Various combination
      therapies which have been attempted in the past to modulate the adriamycin
      induced cardiomyopathy are also discussed. Recently, it has been discovered that
      probucol, a lipid lowering agent and potent antioxidant, provides complete
      protection against adriamycin-induced cardiomyopathy in rats without interfering
      with the anti-tumor properties of this antibiotic. Clinical trials employing
      adriamycin therapy in combination with probucol are needed to determine the
      applied value of these laboratory findings.

PMID- 7563103
TI  - Enhancement of cardiac function by cyclocreatine in models of cardiopulmonary
      bypass.
AB  - This study tests the hypothesis that the administration of cyclocreatine prior to
      global ischemia enhances recovery of cardiac function during reperfusion. Two
      models were used. First, in a Langendorff-working heart model of normothermic
      cardioplegic arrest, rats (n = 6 per group) were injected intravenously with
      saline or cyclocreatine (600, 300, or 150 mg/kg). After 30 min or 2 h, hearts
      were excised and perfused in the Langendorff mode for 5 min and then in the
      working heart mode for 20 min. Normothermic arrest was induced by infusing warm
      St. Thomas solution once; then hearts were kept at 37 degrees C for 40 min.
      Following arrest, hearts were reperfused in the Langendorff mode for 15 min and
      then in the working mode for 30 min. Cyclocreatine consistently produced
      significantly better recovery of aortic flow and cardiac output compared to that
      of saline hearts. Second, in an intact canine model of cold cardioplegic arrest,
      adult mongrel dogs (n = 3 to 6 per group) underwent aortic cross-clamping for 1
      h, followed by reperfusion on bypass for 45 min and off bypass for 4 h. Dogs were
      injected intravenously with saline or cyclocreatine (500 mg/kg) for 1 h before
      experiment. Post-bypass segmental contractility and cardiac output were
      significantly better in cyclocreatine hearts compared to that of controls. In a
      limited study, after a 3 h aortic cross-clamp time, cyclocreatine hearts achieved
      91% baseline function while control hearts failed after 2 h. Results of this
      study suggest that cyclocreatine, without inotropic or chronotropic effect,
      protects the heart from global ischemic injury.

PMID- 7563104
TI  - Characterization and structural organization of the cardiac beta-myosin heavy
      chain gene from Syrian hamster.
AB  - In order to perform comparative studies of the cardiac myosin heavy chain (MyHC)
      genes, we determined the sequence of the Syrian hamster beta-MyHC gene and its 5'
      flanking region. This 33,960 basepair (bp) sequence contains 12,196 bp of the 5'
      flanking region as well as 21,731 bp of the complete beta-MyHC gene, with its 3'
      end overlapping with the alpha-MyHC gene. All the exon/intron boundaries were
      determined and relative to the human beta-MyHC gene, an extra 5' untranslated
      exon was identified. The isolation and sequencing of the Syrian hamster beta-MyHC
      gene may further the understanding about the regulation and the evolution of the
      cardiac MyHC genes.

PMID- 7563105
TI  - Role of protein kinase C in mediating effects of hydrogen peroxide in guinea-pig
      ventricular myocytes.
AB  - The present study examined the effects of hydrogen peroxide (H2O2) on
      intracellular calcium transients and unloaded cell shortening in the presence of
      the protein kinase C (PKC) inhibitors 1-(5-isoquinolinesulfonyl-2
      methylpiperazine (H7) or chelerythrine chloride (CHC) or the PKC activator
      phorbol 12-myristate 13-acetate (PMA). Calcium transient amplitudes and cell
      shortening were measured simultaneously in single, enzymatically dissociated
      ventricular myocytes loaded with fura2-AM. Exposure of myocytes to H2O2, 25
      microM or 75 microM, for 15 min caused a time- and concentration-dependent
      increase in calcium transient amplitude, cell shortening and the diastolic
      340/380 fluorescence ratio. Significant increases in calcium transient amplitude
      were observed from 7 to 15 min of superfusion with 25 microM H2O2 and the
      transient amplitude remained elevated throughout the 10 min washout period. In
      the presence of 75 microM H2O2, transient amplitude was elevated following 2 min
      and remained elevated for the remainder of the experiment. Significant increases
      in cell shortening were also observed from 7 to 15 min in the presence of either
      25 or 75 microM H2O2. This effect was reversed upon washout of the lower
      concentration of H2O2 but persisted during the initial 5 min of washout at the
      higher concentration. The diastolic 340/380 fluorescence ratio was unaltered in
      the presence of 25 microM of H2O2, however this parameter was significantly
      increased from 7 to 15 min following exposure to 75 microM H2O2 and remained
      elevated throughout the washout period. The H2O2-induced increases in calcium
      transient amplitude and cell shortening were significantly attenuated in myocytes
      which were pretreated with either H7 or CHC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563106
TI  - Effects of training on potassium homeostasis during exercise.
AB  - Potassium release from contracting skeletal muscle cells facilitates ongoing
      muscle contraction but may also lead to muscular fatigue. This review focuses on
      the effects of altered physical activity on K+ regulation during exercise, with
      special emphasis on K+ regulation in humans. Endurance and sprint training
      specifically enhance prolonged and high intensity exercise performance,
      respectively. Both forms of training reduce the exercise-induced rise in plasma
      [K+] at the same absolute exercise work rate and duration and increase the total
      concentration of Na+,K+ pumps in trained human muscle by approximately 15%.
      However, the increased pump density has not been proven to account directly for
      either the reduced hyperkalaemia or the improved exercise performance after
      training. The most likely factor accounting for the improved K+ regulation after
      training is an increased activation of Na+,K+ pumps during exercise, but this is
      not due to increased circulating catecholamine concentrations after training. A
      chronic reduction in physical activity reduces the muscle Na+K+ pump
      concentration in animal models, with an augmented exercise-induced rise in plasma
      [K+]. Thus, physical training enhances, whilst inactivity impairs K+ regulation
      during exercise, consistent with the improved exercise performance after physical
      training and the impaired performance with inactivity.

PMID- 7563107
TI  - The anatomy of a molecular giant: how the sarcomere cytoskeleton is assembled
      from immunoglobulin superfamily molecules.
AB  - Cross-striated muscle contains an elastic cytoskeleton comprised of the giant
      protein titin and several associated proteins. cDNA sequencing revealed that all
      these proteins are immunoglobulin superfamily members. This modular structure
      opens the possibility to dissect the proteins involved into functional units and
      to approach the problem of structure-function correlation at the molecular level.

PMID- 7563108
TI  - Preconditioning in man: progress and prospects.

PMID- 7563109
TI  - Preconditioning induced protection against post-ischaemic contractile
      dysfunction: characteristics and mechanisms.

PMID- 7563110
TI  - Fibronectin expression during physiological and pathological cardiac growth.
AB  - Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix of
      most tissues that serves as a bridge between cells and the interstitial collagen
      meshwork and influences diverse processes including cell growth, adhesion,
      migration, and wound repair. Multiple FN forms arise by the alternative splicing
      of a primary transcript originating from a single gene. The spatial and temporal
      alterations in FN expression in the myocardium has been studied in models of
      cardiac growth in vivo such as fetal development, and hypertrophy secondary to
      pressure overload. This review focuses on the differential expression of FN
      isoforms that are observed in different models of cardiac growth. Using a
      combination of qualitative and quantitative analyses it is shown that in the rat
      myocardium: (1) the FN phenotype is developmentally regulated, (2) the re
      expression of the fetal FN isoforms is observed in different models of cardiac
      hypertrophy secondary to a sudden or progressive hypertension and (3) the changes
      in cardiac FN expression affect mostly the coronary artery smooth muscle cells.

PMID- 7563111
TI  - Possibilities for the pharmacological exploitation of ischaemic preconditioning.

PMID- 7563113
TI  - Evolution and recombination of bovine DNA repeats.
AB  - The history of the abundant repeat elements in the bovine genome has been studied
      by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both
      emerged just after the divergence of the Camelidae and the true ruminants. A 31
      bp subrepeat motif in satellites of the Bovidae species cattle, sheep, and goat
      is also present in Cervidae (deer) and apparently predates the Bovidae. However,
      the other components of the bovine satellites were amplified after the divergence
      of the cattle and the Caprinae (sheep and goat). A 23-bp motif, which as
      subrepeat of two major satellites occupies 5% of the cattle genome, emerged only
      after the split of the water buffalo and other cattle species. During the
      evolution of the Bovidae the satellite repeat units were shaped by recombination
      events involving subrepeats, other satellite components, and SINE elements.
      Differences in restriction sites of homologous satellites indicate a continuing
      rapid horizontal spread of new sequence variants.

PMID- 7563112
TI  - Gorilla and orangutan c-myc nucleotide sequences: inference on hominoid
      phylogeny.
AB  - The nucleotide sequences of the gorilla and orangutan myc loci have been
      determined by the dideoxy nucleotide method. As previously observed in the human
      and chimpanzee sequences, an open reading frame (ORF) of 188 codons overlapping
      exon 1 could be deduced from the gorilla sequence. However, no such ORF appeared
      in the orangutan sequence. The two sequences were aligned with those of human and
      chimpanzee as hominoids and of gibbon and marmoset as outgroups of hominoids. The
      branching order in the evolution of primates was inferred from these data by
      different methods: maximum parsimony and neighbor-joining. Our results support
      the view that the gorilla lineage branched off before the human and chimpanzee
      diverged and strengthen the hypothesis that chimpanzee and gorilla are more
      related to human than is orangutan.

PMID- 7563115
TI  - The beta-tubulin gene family evolution in the Drosophila montium subgroup of the
      melanogaster species group.
AB  - The beta 1-, beta 2-, and beta 3-tubulin genes have been mapped by in situ
      hybridization on the polytene chromosomes of 11 selected species (15 strains)
      belonging to the Drosophila montium subgroup. Although the hybridization pattern
      among the strains of the same species does not differ, this pattern is
      significantly different among the species. The beta-tubulin genes in the montium
      subgroup seem to be organized in a cluster, or in a semicluster or are completely
      dispersed. The clustered arrangements is found in the North-Oriental sibling
      species D. auraria, D. triauraria, and D. quadraria. The semiclustered
      arrangement, wherein the beta 1 and beta 2 genes are located at the same locus
      while beta 3 is at a different one, appears in the South-Oriental species D.
      bicornuta, D. serrata, and D. birchii, as well as in the Afrotropical species D.
      diplacantha and D. seguyi. The complete separation of the genes is observed in
      the Indian species D. kikkawai and D. jambulina and in the Afrotropical species
      D. vulcana. Based on the above results, a possible mode of evolution of the beta
      tubulin genes in the montium subgroup is attempted. In addition, phylogenetic
      relationships among the montium species are discussed.

PMID- 7563114
TI  - Concerted evolution of mammalian cardiac myosin heavy chain genes.
AB  - We have recently determined the complete nucleotide sequences of the cardiac
      alpha- and beta-myosin heavy chain (MyHC) genes from both human and Syrian
      hamster. These genomic sequence data were used to study the molecular evolution
      of the cardiac MyHC genes. Between the alpha- and beta-MyHC genes, multiple gene
      conversion events were detected by (1) maximum parsimony tree analyses, (2)
      synonymous substitution analyses, and (3) detection of pairwise identity of
      intron sequences. Approximately half of the 40 cardiac MyHC exons have undergone
      concerted evolution through the process of gene conversion with the other half
      undergoing divergent evolution. Gene conversion occurred more often in exons
      encoding the alpha-helical myosin rod domain than in the globular head domain,
      and an apparent directional bias was also observed, with transfer of genetic
      material occurring more often from beta to alpha.

PMID- 7563116
TI  - Evolution of the bovine lysozyme gene family: changes in gene expression and
      reversion of function.
AB  - Recruitment of lysozyme to a digestive function in ruminant artiodactyls is
      associated with amplification of the gene. At least four of the approximately ten
      genes are expressed in the stomach, and several are expressed in nonstomach
      tissues. Characterization of additional lysozymelike sequences in the bovine
      genome has identified most, if not all, of the members of this gene family. There
      are at least six stomachlike lysozyme genes, two of which are pseudogenes. The
      stomach lysozyme pseudogenes show a pattern of concerted evolution similar to
      that of the functional stomach genes. At least four nonstomach lysozyme genes
      exist. The nonstomach lysozyme genes are not monophyletic. A gene encoding a
      tracheal lysozyme was isolated, and the stomach lysozyme of advanced ruminants
      was found to be more closely related to the tracheal lysozyme than to the stomach
      lysozyme of the camel or other nonstomach lysozyme genes of ruminants. The
      tracheal lysozyme shares with stomach lysozymes of advanced ruminants the
      deletion of amino acid 103, and several other adaptive sequence characteristics
      of stomach lysozymes. I suggest here that tracheal lysozyme has reverted from a
      functional stomach lysozyme. Tracheal lysozyme then represents a second instance
      of a change in lysozyme gene expression and function within ruminants.

PMID- 7563117
TI  - Molecular evolutionary analysis of the YWVZ/7B globin gene cluster of the insect
      Chironomus thummi.
AB  - We report the sequence of 8.1 kb of DNA containing the 3' end of one and seven
      other complete intronless globin genes from the YWVZ/7B locus of the dipteran
      Chironomus thummi thummi. One of these (ctt-v) appears to be a pseudogene by
      virtue of a premature termination codon, whereas the others encode apparently
      functional globin polypeptides. taken together with previously published data,
      the C. th. thummi YWVZ/7B locus codes for at least 11 globins, five of which
      differ from one another by no more than two amino acids. In contrast only nine
      globin genes are found in a comparable genomic clone isolated from C. th. piger.
      As indicated by sequence alignment, this difference in copy number can be
      attributed to a loss of one gene (fusion of globin genes 7B8 and 7B10) in the
      piger lines, coupled with a gain (globin gene 7B9) in the thummi lineage.
      Comparisons between the thummi and piger sequences showed that YWVZ/7B intergenic
      regions have maintained a level of 91% similarity since the thummi/piger
      divergence: most differences are simply due to single base substitutions or
      insertion/deletion events in either the thummi or the piger DNA, but three
      instances of partially overlapping deletions were also detected. A phylogenetic
      analysis of YWVZ/7B gene products was conducted, from which a plausible
      reconstruction of the evolutionary history of the locus was obtained. In
      addition, alignment of globin 7B amino acid sequences suggested that globin genes
      7B2 and 7B3 (reported at the protein and cDNA level, respectively, but not
      contained on the C. th. thummi or C. th. piger genomic clones) are possibly
      chimeric genes. Given the trend toward expansion of the C. thummi globin gene
      family in general and of the globin 7B subfamily in particular, we propose that
      increased copy number of these genes has been positively selected as a mechanism
      to achieve a high Hb concentration in the larval hemolymph.

PMID- 7563118
TI  - Divergence of the phytochrome gene family predates angiosperm evolution and
      suggests that Selaginella and Equisetum arose prior to Psilotum.
AB  - Thirty-two partial phytochrome sequences from algae, mosses, ferns, gymnosperms,
      and angiosperms (11 of them newly released ones from our laboratory) were
      analyzed by distance and character-state approaches (PHYLIP, TREECON, PAUP). In
      addition, 12 full-length sequences were analyzed. Despite low bootstrap values at
      individual internal nodes, the inferred trees (neighbor-joining, Fitch, maximum
      parsimony) generally showed similar branching orders consistent with other
      molecular data. Lower plants formed two distinct groups. One basal group
      consisted of Selaginella, Equisetum, and mosses; the other consisted of a
      monophyletic cluster of frond-bearing pteridophytes. Psilotum was a member of the
      latter group and hence perhaps was not, as sometimes suggested, a close relative
      of the first vascular plants. The results further suggest that phytochrome gene
      duplication giving rise to a- and b- and later to c-types may have taken place
      within seedfern genomes. Distance matrices dated the separation of mono- and
      dicotyledons back to about 260 million years before the present (Myr B.P.) and
      the separation of Metasequoia and Picea to a fossil record-compatible value of
      230 Myr B.P. The Ephedra sequence clustered with the c- or a-type and Metasequoia
      and Picea sequences clustered with the b-type lineage. The "paleoherb" Nymphaea
      branched off from the c-type lineage prior to the divergence of mono- and
      dicotyledons on the a- and b-type branches. Sequences of Piper (another
      "paleoherb") created problems in that they branched off from different
      phytochrome lineages at nodes contradicting distance from the inferred trees'
      origin.

PMID- 7563120
TI  - Kinetics of synonymous codon change for an amino acid of arbitrary degeneracy.
AB  - The kinetics of synonymous codon change and species divergence is described in a
      matrix formalism that is equally applicable to all levels of codon degeneracy and
      all levels of codon or nucleotide bias. Based on the formalism it is possible to
      calculate the sum of all synonymous substitution rate constants from the observed
      sequence differences between two species. This sum, the relaxation rate, is
      equivalent to the Log Det transformation that has recently been proposed as a new
      measure of evolutionary distance (Lockhardt et al. Mol. Biol. Evol. 11(4):605
      612, 1994). The relationship between this measure and the average number of base
      changes per site (Ks) is discussed. The formalism is tested on some sets of
      simulated sequence divergence data.

PMID- 7563121
TI  - Patterns of nucleotide composition at fourfold degenerate sites of animal
      mitochondrial genomes.
AB  - Three statistics (%GC, GC-skew, and AT-skew) can be used to describe the overall
      patterns of nucleotide composition in DNA sequences. Fourfold degenerate third
      codon positions from 16 animal mitochondrial genomes were analyzed. The overall
      composition, as measured by %GC, varies from 3.6 %GC in the honeybee to 47.2 %GC
      in human mtDNA. Compositional differences between strands of the mitochondrial
      genome were quantified using the two skew statistics presented in this paper.
      Strand-specific distribution of bases varies among animal taxa independently of
      overall %GC. Compositional patterns reflect the substitution process. Description
      of these patterns may aid in the formation of hypotheses about substitutional
      mechanisms.

PMID- 7563119
TI  - Structure of the human CRFB4 gene: comparison with its IFNAR neighbor.
AB  - The cytokine receptor family consists of a growing number of structurally and
      evolutionarily related transmembrane receptors. CRFB4 and IFNAR are two of the
      most similar members of this family. They are encoded by two neighboring genes on
      both human chromosome 21 and murine chromosome 16. The sequence of the human
      CRFB4 gene was determined from the first exon to the last intron. The nature of
      the repetitive sequences present in the introns was analyzed and compared with
      those present in the human IFNAR gene. This analysis leads to considerations of
      the antiquity of the duplication that gave rise to both genes from a common
      ancestor. A pseudogene for USF has been identified in the IFNAR gene and a new
      definition for the repetitive sequence MER37 is proposed. The polymorphism
      associated with two CA repeats present in the CRFB4 gene is described.

PMID- 7563122
TI  - Molecular phylogeny of gibbons inferred from mitochondrial DNA sequences:
      preliminary report.
AB  - We analyzed the 896 base-pair (bp) mitochondrial DNA (mtDNA) sequences for seven
      gibbons, representative of three out of four subgenera. The result from our
      molecular analysis is consistent with previous studies as to the monophyly of
      subgenus Hylobates species, yet the relationship among subgenera remains slightly
      ambiguous. A striking result of the analysis is the phylogenetic location of
      Kloss's gibbon (H. klossii). Kloss's gibbon has been considered to be an initial
      offshoot of the subgenus Hylobates because of its morphological primitiveness.
      However, our molecular data strongly suggest that Kloss's gibbon speciated most
      recently within the subgenus Hylobates.

PMID- 7563123
TI  - Evolution according to large ribosomal subunit RNA.
AB  - Evolutionary trees were constructed, by distance methods, from an alignment of
      225 complete large subunit (LSU) rRNA sequences, representing Eucarya, Archaea,
      Bacteria, plastids, and mitochondria. A comparison was made with trees based on
      sets of small subunit (SSU) rRNA sequences. Trees constructed on the set of 172
      species and organelles for which the sequences of both molecules are known had a
      very similar topology, at least with respect to the divergence order of large
      taxa such as the eukaryotic kingdoms and the bacterial divisions. However, since
      there are more than ten times as many SSU as LSU rRNA sequences, it is possible
      to select many SSU rRNA sequence sets of equivalent size but different species
      composition. The topologies of these trees showed considerable differences
      according to the particular species set selected. The effect of the dataset and
      of different distance correction methods on tree topology was tested for both LSU
      and SSU rRNA by repetitive random sampling of a single species from each large
      taxon. The impact of the species set on the topology of the resulting consensus
      trees is much lower using LSU than using SSU rRNA. This might imply that LSU rRNA
      is a better molecule for studying wide-range relationships. The mitochondria
      behave clearly as a monophyletic group, clustering with the Proteobacteria. Gram
      positive bacteria appear as two distinct groups, which are found clustered
      together in very few cases. Archaea behave as if monophyletic in most cases, but
      with a low confidence.

PMID- 7563126
TI  - Pervasive migration of organellar DNA to the nucleus in plants.
AB  - A surprisingly large number of plant nuclear DNA sequences inferred to be
      remnants of chloroplast and mitochondrial DNA migration events were detected
      through computer-assisted database searches. Nineteen independent organellar DNA
      insertions, with a median size of 117 bp (range of 38 to > 785 bp), occur in the
      proximity of 15 nuclear genes. One fragment appears to have been passed through a
      RNA intermediate, based on the presence of an edited version of the mitochondrial
      gene in the nucleus. Tandemly arranged fragments from disparate regions of
      organellar genomes and from different organellar genomes indicate that the
      fragments joined together from an intracellular pool of RNA and/or DNA before
      they integrated into the nuclear genome. Comparisons of integrated sequences to
      genes lacking the insertions, as well as the occurrence of coligated fragments,
      support a model of random integration by end joining. All transferred sequences
      were found in noncoding regions, but the positioning of organellar-derived DNA in
      introns, as well as regions 5' and 3' to nuclear genes, suggests that the random
      integration of organellar DNA has the potential to influence gene expression
      patterns. A semiquantitative estimate was performed on the amount of organellar
      DNA being transferred and assimilated into the nucleus. Based on this database
      survey, we estimate that 3-7% of the plant nuclear genomic sequence files contain
      organellar-derived DNA. The timing and the magnitude of genetic flux to the
      nuclear genome suggest that random integration is a substantial and ongoing
      process for creating sequence variation.

PMID- 7563124
TI  - Translation elongation factor-3 (EF-3): an evolving eukaryotic ribosomal protein?
AB  - Fungi appear to be unique in their requirement for a third soluble translation
      elongation factor. This factor, designated elongation factor 3 (EF-3), exhibits
      ribosome-dependent ATPase and GTPase activities that are not intrinsic to the
      fungal ribosome but are nevertheless essential for translation elongation in
      vivo. The EF-3 polypeptide has been identified in a wide range of fungal species
      and the gene encoding EF-3 (YEF3) has been isolated from four fungal species
      (Saccharomyces cerevisiae, Candida albicans, Candida guillermondii, and
      Pneumocystis carinii). Computer-assisted analysis of the predicted S. cerevisiae
      EF-3 amino acid sequence was used to identify several potential functional
      domains; two ATP binding/catalytic domains conserved with equivalent domains in
      members of the ATP-Binding Cassette (ABC) family of proteins, an amino-terminal
      region showing significant similarity to the E. coli S5 ribosomal protein, and
      regions of predicted interaction with rRNA, tRNA, and mRNA. Furthermore, EF-3 was
      also found to display amino acid similarity to myosin proteins whose cellular
      function is to provide the motive force of muscle. The identification of these
      regions provides clues to both the evolution and function of EF-3. The predicted
      functional regions are conserved among all known fungal EF-3 proteins and a
      recently described homologue encoded by the Chlorella virus CVK2. We propose that
      EF-3 may play a role in the ribosomal optimization of the accuracy of fungal
      protein synthesis by altering the conformation and activity of a ribosomal
      "accuracy center," which is equivalent to the S4-S5-S12 ribosomal protein
      accuracy center domain of the E. coli ribosome. Furthermore, we suggest that EF-3
      represents an evolving ribosomal protein with properties analogous to the
      intrinsic ATPase activities of higher eukaryotic ribosomes, which has wider
      implications for the evolutionary divergence of fungi from other eukaryotes.

PMID- 7563125
TI  - Primary structure and eubacterial relationships of the pyruvate:ferredoxin
      oxidoreductase of the amitochondriate eukaryote Trichomonas vaginalis.
AB  - In the eukaryotic unicellular organism Trichomonas vaginalis a key step of energy
      metabolism, the oxidative decarboxylation of pyruvate with the formation of
      acetyl-CoA, is catalyzed by the iron-sulfur protein pyruvate:ferredoxin
      oxidoreductase (PFO) and not by the almost-ubiquitous pyruvate dehydrogenase
      multienzyme complex. This enzyme is localized in the hydrogenosome, an organelle
      bounded by a double membrane. PFO and its closely related homolog,
      pyruvate:flavodoxin oxidoreductase, are enzymes found in a number of
      archaebacteria and eubacteria. The presence of these enzymes in eukaryotes is
      restricted, however, to a few amitochondriate groups. To gain more insight into
      the evolutionary relationships of T. vaginalis PFO we determined the primary
      structure of its two genes (pfoA and pfoB). The deduced amino acid sequences
      showed 95% positional identity. Motifs implicated in related enzymes in liganding
      the Fe-S centers and thiamine pyrophosphate were well conserved. The T. vaginalis
      PFOs were found to be homologous to eubacterial pyruvate:flavodoxin
      oxidoreductases and showed about 40% amino acid identity to these enzymes over
      their entire length. Lack of eubacterial PFO sequences precluded a comparison.
      pfoA and pfoB revealed a greater distance from related enzymes of Archaebacteria.
      The conceptual translation of the nucleotide sequences predicted an amino
      terminal pentapeptide not present in the mature protein. This processed leader
      sequence was similar to but shorter than leader sequences noted in other
      hydrogenosomal proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563127
TI  - Molecular and phylogenetic analysis of PCR-amplified cyclin-dependent kinase
      (CDK) family sequences from representatives of the earliest available lineages of
      eukaryotes.
AB  - Cyclin-dependent kinase (CDK) and cell division control (CDC2) sequences are
      strongly conserved among eukaryotes and may complement the use of other sequence
      families in eukaryotic phylogenetic inference. We synthesized degenerate PCR
      primers to amplify the catalytic region of CDK homologs in representatives of the
      earliest available lineages of eukaryotes. CDK family sequence-based, maximum
      likelihood distance measurements with neighbor-joining, and Fitch-Margoliash
      least-squares analyses produced unrooted dendrograms that included protists,
      yeasts, and higher eukaryotes. Bootstrap confidence estimates supported CDK-based
      phylogenetic groupings among the protists, fungi, and vertebrates although
      resolution within these groups was often insignificant. However, Trichomonas
      vaginalis and Giardia lamblia exhibited two of the most divergent CDK-like
      sequences consistent with rRNA-phylogenetic inference of early divergence of
      these eukaryotic lineages. In the evolution from unicellular to multicellular
      organisms, a constellation of amino acid residues aligning with the human, CDK N
      terminal beta sheet may have undergone abrupt replacement.

PMID- 7563128
TI  - A Drosophila hsp70 gene contains long, antiparallel, coupled open reading frames
      (LAC ORFs) conserved in homologous loci.
AB  - A clone isolated from a Drosophila auraria heat-shock cDNA library presents two
      long, antiparallel, coupled (LAC) open reading frames (ORFs). One strand ORF is
      1,929 nucleotides long and exhibits great identity (87.5% at the nucleotide level
      and 94% at the amino acid level) with the hsp70 gene copies of D. melanogaster,
      while the second strand ORF, in antiparallel in-frame register arrangement, is
      1,839 nucleotides long and exhibits 32% identity with a putative, recently
      identified, NAD(+)-dependent glutamate dehydrogenase (NAD(+)-GDH). The overlap of
      the two ORFs is 1,824 nucleotides long. Computational analysis shows that this
      LAC ORF arrangement is conserved in other hsp70 loci in a wide range of
      organisms, raising questions about possible evolutionary benefits of such a
      peculiar genomic organization.

PMID- 7563130
TI  - Evolutionary divergence of the cytochrome b5 gene of Drosophila.
AB  - Cytochrome proteins perform a broad spectrum of biological functions ranging from
      oxidative metabolism to electron transport and are thus essential to all
      organisms. The b-type cytochrome proteins bind heme noncovalently, are expressed
      in many different forms and are localized to various cellular compartments. We
      report the characterization of the cytochrome b5 (Cyt-b) gene of Drosophila
      virilis and compare its structure to the Cyt-b gene of Drosophila melanogaster.
      As in D. melanogaster, the D. virilis gene is nuclear encoded and single copy.
      Although the intron/exon structures of these homologues differ, the Cyt-b
      proteins of D. melanogaster and D. virilis are approximately 75% identical and
      share the same size coding regions (1,242 nucleotides) and protein products (414
      amino acids). The Drosophila Cyt-b proteins show sequence similarity to other b
      type cytochromes, especially in the N-terminal heme-binding domain, and may be
      targeted to the mitochondrial membrane. The greatest levels of similarity are
      observed in areas of potential importance for protein structure and function. The
      exon sequences of the D. virilis Cyt-b gene differ by a total of 292 base
      changes. However, 62% of these changes are silent. The high degree of
      conservation between species separated by 60 million years of evolution in both
      the DNA and amino acid sequences suggests this nuclear cytochrome b5 locus
      encodes an essential product of the Drosophila system.

PMID- 7563129
TI  - Molecular evolution of the genes encoding receptor tyrosine kinase with
      immunoglobulinlike domains.
AB  - Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobulinlike
      domains in their extracellular regions are classified as subclasses III, IV, and
      V, respectively. Conservation of the exon/intron structure of the downstream part
      of the human KIT, FMS, and FLT3 genes that encode RTK of subclass III together
      with the particular chromosomal localization of these genes suggests that RTKIII
      genes have evolved from a common ancestor by cis and trans duplications. To
      strengthen this model of evolution and to determine if it can be extended to
      RTKIV and V genes, we constructed a phylogenetic tree of RTKIII, IV, and V on the
      basis of a multiple alignment of their catalytic tyrosine kinase domain sequences
      and determined the exon/intron structure of PDGFRA (subclass III), FGFR4
      (subclass IV), and FLT4 (subclass V) genes in their downstream part. Phylogenetic
      analyses with amino acid or nucleotide sequences both resulted in one most
      parsimonious tree. The phylogenetic trees obtained indicate that all three
      subclasses are well individuated and that RTKIII and RTKV are closer to each
      other than RTKIV. Furthermore, RTKIII and FLT4 (subclass V) genes possess the
      same exon/intron structure in their downstream part while the structure of the
      RTKIV genes is very similar to that of RTKIII and FLT4. Both approaches are in
      complete agreement and indicate that RTKIII, IV, and V genes most probably
      evolved from a common ancestor already "in pieces" by successive duplications
      involving entire genes.

PMID- 7563131
TI  - Sex in Escherichia coli does not disrupt the clonal structure of the population:
      evidence from random amplified polymorphic DNA and restriction-fragment-length
      polymorphism.
AB  - Analysis of the Escherichia coli population by multilocus enzyme electrophoresis
      (MLEE) has established its clonal organization, but there is increasing evidence
      that horizontal DNA transfer occurs in E. coli. We have assessed the genetic
      structure of the species E. coli and determined the extent to which recombination
      can affect the clonal structure of bacteria. A panel of 72 E. coli strains from
      the ECOR collection was characterized by random amplified polymorphic DNA (RAPD)
      and restriction-fragment-length polymorphism (RFLP) of the ribosomal RNA gene
      (rrn) regions. These strains have been characterized by MLEE and are assumed to
      reflect the range of genotypic variation in the species as a whole. Statistical
      analysis, including factorial analysis of correspondence (FAC) and hierarchical
      classifications, established that the data obtained with the three genetic
      markers are mutually corroborative, thus providing compelling evidence that
      horizontal transfer does not disrupt the clonal organization of the population.
      However, there is a gradient of correlation between the different classifications
      which ranges from the highly clonal structure of B2 group strains causing
      extraintestinal infections in humans to the less-stringent structure of B1 group
      strains that came mainly from nonprimate mammals. This group (B1) appears to be
      the framework from which the remaining non-A group strains have emerged. These
      results indicate that RAPD analysis is well suited to intraspecies
      characterization of E. coli. Lastly, treating the RAPD data by FAC allowed
      description of subgroup-specific DNA fragments which can be used, in a strategy
      comparable to positional cloning, to isolate virulence genes.

PMID- 7563132
TI  - Synonymous substitution-rate constants in Escherichia coli and Salmonella
      typhimurium and their relationship to gene expression and selection pressure.
AB  - Based on the differences in synonymous codon use between E. coli and S.
      typhimurium, the synonymous substitution rates can be estimated. In contrast to
      previous studies on the substitution rates in these two organisms, we use a
      kinetic model that explicitly takes the selection bias into account. The
      selection pressure on synonymous codons for a particular amino acid can be
      calculated from the observed codon bias. This offers a unique opportunity to
      study systematically the relationship between substitution-rate constants and
      selection pressure. The results indicate that the codon bias in these organisms
      is determined by a mutation-selection balance rather than by stabilizing
      selection. A best fit to the data implies that the mutation rate constant
      increases about threefold in genes at low expression levels relative to those
      that are highly expressed.

PMID- 7563133
TI  - Evolution of seed storage protein genes: legumin genes of Ginkgo biloba.
AB  - Legumin-like seed storage proteins have been intensively studied in crop plants.
      However, little is known about the molecular evolution of these proteins and
      their genes and it was assumed that they originated from an ancestral gene that
      already existed at the beginning of angiosperm evolution. We have evidence for
      the ubiquitous occurrence of homologous proteins in gymnosperms as well. We have
      characterized the major seed storage globulin from Ginkgo biloba by amino acid
      sequencing, which reveals clear homology to legumin-like proteins from
      angiosperms. The Ginkgo legumin is encoded by a gene family; we describe two of
      its members. The promoter regions contain sequence motifs which are known to
      function as regulatory elements involved in seed-specific expression of
      angiosperm legumins, although the tissues concerned are different in gymnosperms
      and angiosperms. The Ginkgo legumin gene structure is divergent from that of
      angiosperms and suggests that the evolution of legumin genes implicated loss of
      introns. From our data and from functional approaches recently described it
      becomes obvious that the posttranslational processing site of legumin precursors
      is less conserved than hitherto assumed. Finally, we present a phylogenetic
      analysis of legumin encoding sequences and discuss their utility as molecular
      markers for the reconstruction of seed plant evolution.

PMID- 7563134
TI  - The Sex-lethal gene homologue in Chrysomya rufifacies is highly conserved in
      sequence and exon-intron organization.
AB  - A great variety of sex determination mechanisms exists in insect species. In
      Drosophila melanogaster sex is determined by the ratio between X chromosomes and
      autosomes, while in the blowfly Chrysomya rufifacies it is maternally determined.
      A cascade of genes which are involved in sex determination has been identified in
      D. melanogaster with the Sex-lethal gene (Sxl) as the key gene. We screened
      genomic libraries of C. rufifacies with a probe of the Sxl gene from D.
      melanogaster and isolated a genomic region that included most of the homologous
      gene. DNA- and protein-sequence comparison showed a high percent identity between
      the Chrysomya and the Drosophila gene. Up to 90% identity of the amino acid
      sequences was found in the region that contained the RNA-binding domains. The
      degree of identity is much lower outside of this functionally important region
      (18% identity). cDNA analysis showed a highly conserved exon-intron structure
      between the two species, although sex-specific splicing as used in D.
      melanogaster for the regulation of Sxl activity, could not be detected in C.
      rufifacies.

PMID- 7563135
TI  - Sequence diversification and exon inactivation in the glycophorin A gene family
      from chimpanzee to human.
AB  - In humans, the allelic diversity of MNSs glycophorins (GP) occurs mainly through
      the recombinational modulation of silent exons (pseudoexons) in duplicated genes.
      To address the origin of such a mechanism, structures of GPA, GPB, and GPE were
      determined in chimpanzee, the only higher primate known to have achieved a three
      gene framework as in humans. Pairwise comparison of the chimpanzee and human
      genes revealed a high degree of sequence identity and similar exon-intron
      organization. However, the chimpanzee GPA gene lacks a completely formed M- or N
      defining sequence as well as a consensus sequence for the Asn-linked
      glycosylation. In the case of the GPB gene, exon III is expressed in the
      chimpanzee but silenced, as a pseudoexon, in the human. Therefore, the protein
      product in the chimpanzee bears a larger extracellular domain than in the human.
      For the GPE genes, exon III and exon IV have been inactivated by identical donor
      splice-site mutations in the two species. Nevertheless, the chimpanzee GPE-like
      mRNA appeared to be transcribed from a GPB/E composite gene containing no 24-bp
      insertion sequence in exon V for the transmembrane domain. These results suggest
      a divergent processing of exonic units from chimpanzee to human in which the
      inactivation of GPB exon III preserved a limited sequence repertoire for
      diversification of human glycophorins.

PMID- 7563136
TI  - Presence and abundance of CENP-B box sequences in great ape subsets of primate
      specific alpha-satellite DNA.
AB  - CENP-B, a highly conserved centromere-associated protein, binds to alpha
      satellite DNA, the centromeric satellite of primate chromosomes, at a 17-bp
      sequence, the CENP-B box. By fluorescence in situ hybridization (FISH) with an
      oligomer specific for the CENP-B box sequence, we have demonstrated the abundance
      of CENP-B boxes on all chromosomes (except the Y) of humans, chimpanzee, pygmy
      chimpanzee, gorilla, and orangutan. This sequence motif was not detected in the
      genomes of other primates, including gibbons, Old and New World monkeys, and
      prosimians. Our results indicate that the CENP-B box containing subtype of alpha
      satellite DNA may have emerged recently in the evolution of the large-bodied
      hominoids, after divergence of the phylogenetic lines leading to gibbons and
      apes; the box is thus on the order of 15-25 million years of age. The rapid
      process of dispersal and fixation of the CENP-B box sequence throughout the human
      and great ape genomes is thought to be a consequence of concerted evolution of
      alpha-satellite subsets on both homologous and nonhomologous chromosomes.

PMID- 7563137
TI  - Polymorphism, monomorphism, and sequences in conserved microsatellites in primate
      species.
AB  - Dimeric short tandem repeats are a source of highly polymorphic markers in the
      mammalian genome. Genetic variation at these hypervariable loci is extensively
      used for linkage analysis, for the identification of individuals, and may be
      useful for interpopulation and interspecies studies. In this paper, we analyze
      the variability and the sequences of a segment including three microsatellites,
      first described in man, in several species of primates (chimpanzee, orangutan,
      gibbon, and macaque) using the heterologous primers (man primers). This region is
      located on the human chromosome 6p, near the tumor necrosis factor genes, in the
      major histocompatibility complex. The fact that these primers work in all species
      studied indicates that they are conserved throughout the different lineages of
      the two superfamilies, the Hominoidea and the Cercopithecidea, represented by the
      macaques. However, the intervening sequence displays intraspecific and
      interspecific variability. The sites of base substitutions and the
      insertion/deletion events are not evenly distributed within this region. The data
      suggest that it is necessary to have a minimal number of repeats to increase the
      rate of mutation sufficiently to allow the development of polymorphism. In some
      species, the microsatellites present single base variations which reduce the
      number of contiguous repeats, thus apparently slowing the rate of additional
      slippage events. Species with such variations or a low number of repeats are
      monomorphic. These microsatellite sequences are informative in the comparison of
      closely related species and reflect the phylogeny of the Old World monkeys, apes,
      and man.

PMID- 7563138
TI  - T-DNA integrations in a new family of repetitive elements of Nicotiana tabacum.
AB  - A number of T-DNA insertions in the genome of Nicotiana tabacum were
      characterized. One class of integrations was found to have occurred in a new
      family of highly repetitive sequences. Three genomic regions (ecoA, ecoB, and
      ecoC) were isolated, all of which contain basic units of 180 bp, organized in
      direct tandem repeats. Several of the 180-bp elements contain an EcoRI
      recognition site within the repeating unit and are therefore named "eco repeats."
      All members of this family are weakly homologous in sequence to a previously
      described class of repeat elements which contained a BamHI site (HRS60 repeat
      family), which suggests that both groups of sequences are of common evolutionary
      origin. The allotetraploid genome of N. tabacum is presumed to originate from the
      hybridization of two diploid genomes. The HRS60 elements previously described
      have been found exclusively in the genome of one of the ancestors, N. sylvestris,
      and in N. tabacum itself. Our DNA hybridization data suggest that the eco
      elements originate from the genome of the other ancestor, N. tomentosiformis.
      Whereas the HRS60 elements are transcriptionally silent, at least some eco
      elements appear to be transcribed.

PMID- 7563141
TI  - Putting the "informed" in informed consent about mammography.

PMID- 7563140
TI  - Phylogeny reconstruction for protein sequences based on amino acid properties.
AB  - This paper presents an essentially new method used to construct phylogenetic
      trees from related amino acid sequences. The method is based on a new distance
      measure which describes sequence relationships by means of typical steric and
      physicochemical properties of the amino acids and is advantageous in some
      essential points. The method was applied to different sets of protein sequences
      and the results were compared with other well-established methods.

PMID- 7563142
TI  - Body wars: effect of friendly fire (cancer therapy)

PMID- 7563143
TI  - Genetic clues about colon cancer reshape treatment approaches.

PMID- 7563144
TI  - Scientists show that invasive breast cancer develops from early cancer cells.

PMID- 7563139
TI  - Fundulus heteroclitus vitellogenin: the deduced primary structure of a piscine
      precursor to noncrystalline, liquid-phase yolk protein.
AB  - We have cloned and sequenced a cDNA encoding a vitellogenin (Vtg) from the
      mummichog, Fundulus heteroclitus, an estuarine teleost. We constructed a liver
      cDNA library against RNA from estrogen-treated male mummichogs. Five overlapping
      cDNA clones totalling 5,197 bp were isolated through a combination of degenerate
      oligonucleotide probing of the library and PCR. The cDNA sequence contains a
      5,112 bp open reading frame. The predicted primary structure of the deduced 1,704
      amino-acid protein is 30-40% identical to other documented chordate Vtgs,
      establishing this Vtg as a member of the ancient Vtg gene family. Of the
      previously reported chordate Vtg sequences (Xenopus laevis, Gallus domesticus,
      Ichthyomyzon unicuspis, and Acipenser transmontanus), all four act as precursor
      proteins to a yolk which is eventually rendered insoluble under physiological
      conditions, either as crystalline platelets or as noncrystalline granules. The
      yolk of F. heteroclitus, on the other hand, remains in a soluble state throughout
      oocyte growth. The putative F. heteroclitus Vtg contains a polyserine region with
      a relative serine composition that is 10-20% higher than that observed for the
      other Vtgs. The trinucleotide repeats encoding the characteristic polyserine
      tracts of the phosvitin region follow a previously reported trend: TCX codons on
      the 5' end and AGY codons toward the 3' end. Whether the difference in Vtg
      primary structure between F. heteroclitus and that of other chordates is
      responsible for the differences in yolk structure remains to be elucidated. As
      the first complete teleost Vtg to be reported, these data will aid in designing
      nucleotide and immunological probes for detecting Vtg as a reproductive status
      indicator in F. heteroclitus and other piscine species.

PMID- 7563145
TI  - Researchers transfer immunity to a woman with cancer.

PMID- 7563146
TI  - Enthusiasm for quality-of-life research rises.

PMID- 7563147
TI  - Experts warn of health risks from loss of biodiversity.

PMID- 7563148
TI  - Are drugs from the jungle cheaper to develop?

PMID- 7563149
TI  - Perceptions of breast cancer risk and screening effectiveness in women younger
      than 50 years of age.
AB  - BACKGROUND: The National Cancer Institute has recently changed its approach and
      has substituted summary-of-evidence statements for specific recommendations for
      breast cancer screening in women 40-50 years of age, leaving these women with a
      greater share of decision-making responsibility. To make an informed decision
      about breast cancer screening, women need accurate information about their breast
      cancer risk and the benefit of screening. Although it has been suggested that
      women younger than 50 years of age overestimate this risk and benefit, their
      estimates have not been quantified. PURPOSE: The purpose of this study was to
      determine how women 40-50 years of age perceive their risk of breast cancer and
      the effectiveness of screening and how these perceptions compare with estimates
      derived from epidemiologic studies of breast cancer incidence and randomized
      clinical trials of screening. METHODS: We mailed a questionnaire to 200 women,
      identified through the computerized medical records of Dartmouth-Hitchock Medical
      Center, who were between 40 and 50 years of age and had no history of breast
      cancer. Each woman was asked about her risk factors for breast cancer and asked
      to estimate her probabilities of developing breast cancer and dying of it within
      10 years, with and without screening. The women's answers were compared with
      individual probabilities derived from the Gail et al. model, age-specific
      probabilities of developing and dying of breast cancer in the United States, and
      the results of randomized clinical trials of screening. RESULTS: The mailed
      questionnaire was completed and returned by 145 (73%) of the 200 women.
      Respondents over-estimated their probability of dying of breast cancer within 10
      years by more than 20-fold (median, 22.3; interquartile range, 11.1-74.2).
      Assuming a 10% relative risk reduction from screening, respondents overestimated
      the relative risk reduction by sixfold (median, 6.0; interquartile range, 5.0
      7.5) and the absolute risk reduction more than 100-fold (median, 127.5;
      interquartile range, 47.1-399.6). The median perceived estimate of absolute risk
      reduction was 6.0 breast cancer deaths per 100 women; the median calculated
      estimate was only 0.04 per 100 women. CONCLUSION: These findings suggest that
      many women younger than 50 years of age substantially overestimate their breast
      cancer risk and the effectiveness of screening. IMPLICATIONS: A balanced
      presentation of information about breast cancer risk and screening effectiveness
      may improve decision making for women younger than 50 years of age and reduce
      their anxiety about breast cancer, regardless of whether they choose to be
      screened.

PMID- 7563150
TI  - Incidence of second cancers in patients treated for Hodgkin's disease.
AB  - BACKGROUND: Numerous studies of treatment for Hodgkin's disease have demonstrated
      large increases in the incidence of leukemia in the early years following
      chemotherapy, although the duration of effect and the specific agents involved
      are not well understood. Also, some, but not all, studies have indicated that the
      incidence of certain solid tumors increases following treatment for Hodgkin's
      disease. PURPOSE: We studied the association between treatment for Hodgkin's
      disease and the incidence of second cancers. METHODS: We conducted a study within
      a cohort that included 10,472 patients from 14 cancer centers in the United
      States and Canada who were first diagnosed as having Hodgkin's disease at some
      point from 1940 through 1987. Discounting the 1st year after diagnosis, the
      average length of follow-up was 7.1 years per subject. RESULTS: We observed 122
      leukemias and 438 solid tumors. The relative risk (RR) of leukemia following
      chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI]
      = 5.6-35). Increased risks of leukemia were observed after treatment with
      chlorambucil (RR = 2.0; 95% CI = 1.1-3.6), procarbazine (RR = 4.9; 95% CI = 2.6
      9.1), vinblastine (RR = 1.7; 95% CI = 1.1-2.8), and a group of rarely used drugs
      that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI
      = 1.9-7.4). RRs were also estimated for various combinations of drugs, including
      MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95%
      CI = 2.9-12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (RR
      = 1.5; 95% CI = 0.7-3.4). The RR of leukemia associated with splenectomy was 1.6
      (95% CI = 1.0-2.5). The RR of solid tumors following chemotherapy was 1.4 (95% CI
      = 1.1-1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1
      (95% CI = 1.7-5.8). Chemotherapy was associated with an increased risk of cancers
      of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI =
      1.7-20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1-3.2).
      In patients followed for 10 or more years after radiotherapy, increased risks
      were found for cancers of the respiratory system and intrathoracic organs (RR =
      2.7; 95% CI = 1.1-6.8) and for cancers of the female genital system (RR = 2.4;
      95% CI = 1.1-5.4). CONCLUSIONS: Procarbazine, chlorambucil, and vinblastine are
      associated with increased leukemia risk. Combination drug regimens have
      leukemogenic effects estimated as the product of RRs for individual drugs.
      Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the
      effect of chemotherapy on solid tumor risk is weaker than the leukemogenic
      effect. IMPLICATIONS: Without doubt, the benefits of treatment of Hodgkin's
      disease outweigh the risk of a subsequent malignancy, but data on the
      carcinogenic effects of radiation and drugs beyond 10 years after treatment
      continue to be sparse, and future analyses should be directed at long-term
      survivors.

PMID- 7563151
TI  - Genetic alterations at 5p15: a potential marker for progression of precancerous
      lesions of the uterine cervix.
AB  - BACKGROUND: Development of uterine cervical cancer is preceded by preneoplastic
      proliferative changes in the cervical epithelium called "intra-epithelial
      neoplasia" or "dysplasia." The genetic basis of the origin and progression of
      such preneoplastic lesions is not known. By analysis of carcinomas for loss of
      constitutional heterozygosity (LOH), we have previously shown a high frequency of
      allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a
      candidate tumor suppressor gene located in 5p and associated with the development
      of this tumor. PURPOSE: To further understand the role of genetic alterations
      that affect 5p in cervical carcinogenesis, we evaluated the status of
      microsatellite polymorphisms at five loci mapped to 5p14-ter in precancerous and
      cancerous lesions. METHODS: Biopsy specimens from two groups of patients were
      analyzed for genetic alterations affecting 5p. One group comprised 14 cases of
      precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ
      (CIS); the second group comprised 46 previously untreated patients with invasive
      carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for
      genetic losses and instability at five polymorphic microsatellite loci (D5S392,
      D5S406, D5S208, D5S117, and D5S432) mapped to 5p. RESULTS: LOH was observed in 25
      (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS,
      and three (21%) of 14 precancerous lesions. Among the loci tested, D5S406 (5p15.1
      15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three
      cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be
      the site in 5p of the novel candidate tumor suppressor gene. In addition,
      replication error-type alterations were noted in the 5p14-ter region in six (13%)
      of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14
      precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12
      instances that showed microsatellite instability. CONCLUSION: These observations
      suggest that allelic loss and microsatellite instability in the region of D5S406
      may play a role early in the development of cervical carcinoma and identify the
      site of a candidate tumor suppressor gene. These genetic markers (allelic loss
      and microsatellite instability) may also define CIS and precancerous lesions at
      high risk for progression to invasive cancer. IMPLICATIONS: The future molecular
      cloning of the candidate tumor suppressor gene at 5p15.1-15.2 may provide new
      insights into the genetic mechanisms of cervical carcinogenesis. Analysis and
      clinical follow-up of a large cohort of prospectively ascertained cases of
      precancerous lesions would help to validate the usefulness of these markers.

PMID- 7563152
TI  - Comparison of the effects of a pure steroidal antiestrogen with those of
      tamoxifen in a model of human breast cancer.
AB  - BACKGROUND: Tamoxifen, a nonsteroidal estrogen antagonist, is the most prescribed
      drug for the treatment of breast cancer. The use of tamoxifen is limited,
      however, by the development of resistance to this compound in most patients.
      Although tamoxifen behaves primarily as an estrogen antagonist, it has agonist
      (or growth-stimulatory) activity as well. ICI 182,780 is a 7 alpha-alkylsulfinyl
      analogue of estradiol lacking agonist activity. The absence of agonist activity
      may make this steroidal antiestrogen superior to tamoxifen in suppressing tumor
      cell growth. PURPOSE: We compared the inhibitory effects of ICI 182,780,
      tamoxifen, and estrogen withdrawal on the growth of established tumors and on
      tumorigenesis in a model system that uses estrogen-dependent, human MCF-7 breast
      tumor cells growing in athymic nude mice. We also studied the hormonal
      responsiveness of tumors that became resistant to the two estrogen antagonists
      and the effects of these drugs on estrogen-regulated gene expression. METHODS:
      MCF-7 cells were injected subcutaneously into the flanks of castrated, female
      nude mice. The effects of repeated doses of tamoxifen and ICI 182,780 (500
      micrograms and 5 mg, respectively) on the growth of established tumors (8-10 mm
      in size) were determined after supplemental estrogen was removed. The effects of
      antiestrogen treatments on the process of tumorigenesis, in the absence of
      estrogen supplementation, were determined by initiating drug administration on
      the same day as tumor cell inoculation. To evaluate the hormonal responsiveness
      of tumors resistant to tamoxifen and ICI 182,780, 1-mm3 segments of the tumors
      were transplanted onto the flanks of new recipient mice, which were then treated
      with estrogen or the antiestrogens--alone or in combination. Tumor growth was
      monitored by measuring tumor volumes twice a week. Expression of the estrogen
      responsive genes, pLIV1 and pS2, in the tumors of treated animals was analyzed
      using blots of total cellular RNA and complementary DNA probes. RESULTS:
      Treatment with ICI 182,780 suppressed the growth of established tumors twice as
      long as treatment with tamoxifen or estrogen withdrawal. Tumorigenesis, in the
      absence of supplemental estrogen, was delayed to a greater extent in ICI 182,780
      treated mice than in tamoxifen-treated mice. ICI 182,780 was found to be more
      effective than tamoxifen in reducing the expression of estrogen-regulated genes.
      Most tumors eventually became resistant to ICI 182,780 and grew independently of
      estrogen. CONCLUSIONS: ICI 182,780 is a more effective estrogen antagonist than
      tamoxifen in the MCF-7 tumor cell/nude mouse model system.

PMID- 7563153
TI  - Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor
      response to tamoxifen therapy in recurrent breast cancer.
AB  - BACKGROUND: Urokinase-type plasminogen activator (uPA) is a proteolytic enzyme
      thought to be involved in processes leading to tumor cell invasion of surrounding
      tissues. Its activity during metastasis may be regulated by an inhibitor, PAI-1.
      Previous work has shown that high levels of uPA and PAI-1 are associated with
      poor prognosis in primary breast cancers. PURPOSE: In this pilot study, we
      explored possible associations between the expression levels of uPA or PAI-1 and
      the efficacy of tamoxifen treatment in breast cancer patients with relapsed
      disease. METHODS: Levels of uPA, PAI-1, estrogen receptor (ER), and progesterone
      receptor (PgR) were assayed in cytosolic extracts derived from the primary breast
      tumors of 235 tamoxifennaive patients who had recurrent disease. The extracts
      were classified as positive or negative for each assayed factor. In some
      analyses, ER and PgR levels were evaluated together. In these analyses, three
      ER/PgR subsets were defined: low, intermediate, and high. All patients in the
      study received tamoxifen therapy upon relapse (median follow-up, 57 months).
      Association of the tested factors with the response to tamoxifen treatment was
      studied by logistic regression analysis. Association of the factors with
      progression-free and overall survival was further evaluated by Cox univariate and
      multivariate regression analyses. RESULTS: Patients with uPA-negative tumors
      exhibited a better response (tumor regression or stable disease, maintained for
      more than 6 months) to tamoxifen treatment than those with uPA-positive tumors
      (51% versus 26% response; odds ratio [OR] = 0.34; 95% confidence interval [CI] =
      0.18-0.65). The response rate was also better for patients with PAI-1-negative
      tumors than for those with PAI-1-positive tumors (49% versus 35% response; OR =
      0.57; 95% CI = 0.32-1.01). In addition, patients with uPA-positive or PAI-1
      positive tumors showed shorter progression-free survival (P = .001 and P < .05,
      respectively) and total survival after relapse (P = .005 and P < .005,
      respectively). When patients were stratified by ER/PgR status, the only
      statistically significant association between uPA levels and reduced tamoxifen
      response was seen in the subset whose tumors possessed intermediate levels of
      ER/PgR (16% response in uPA-positive versus 60% response in uPA-negative tumors;
      OR = 0.13; 95% CI = 0.04-0.41). Overall, uPA status appeared independent of
      association with ER/PgR status in its ability to predict response to tamoxifen
      treatment. The association of PAI-1 expression and the response to tamoxifen was
      less pronounced when patients were stratified by ER/PgR status. CONCLUSION:
      Measurement of primary breast tumor uPA levels may be useful in predicting the
      overall response of metastatic disease to tamoxifen therapy.

PMID- 7563155
TI  - Helicobacter pylori seroprevalence and colorectal neoplasia: evidence against an
      association.

PMID- 7563154
TI  - Differential inactivation of CDKN2 and Rb protein in non-small-cell and small
      cell lung cancer cell lines.
AB  - BACKGROUND: The CDKN2 gene encodes the human cyclin-dependent kinase 4 inhibitor.
      This inhibitor protein is believed to be a tumor suppressor that plays an
      essential role in cell cycle regulation. One half of all cancer cell lines and
      one fourth of lung cancer cell lines examined to date contain homozygous
      deletions (i.e., both alleles lost) of CDKN2. However, the relative frequency of
      homozygous CDKN2 deletions in non-small-cell lung cancers (NSCLC) and in small
      cell lung cancers (SCLC) has not been determined. Inactivation or loss of another
      tumor suppressor encoded by the retinoblastoma gene (the Rb protein) is more
      common in SCLC than in NSCLC. PURPOSE: We measured the frequency of homozygous
      CDKN2 deletions in 77 NSCLC and in 93 SCLC tumor cell lines. In addition,
      possible associations were explored between CDKN2 gene loss, the presence or
      absence of Rb protein, and the clinical status of lung cancer patients. METHODS:
      DNA was isolated from each tumor cell line and from the primary tumor and normal
      tissue of one NSCLC patient. Sequences corresponding to exons 1 and 2 of the
      CDKN2 gene were amplified by use of the polymerase chain reaction, and the
      resulting amplification products were analyzed by agarose gel electrophoresis and
      DNA blotting. Genomic DNA blotting was also used to evaluate CDKN2 gene
      deletions. The frequency of homozygous CDKN2 loss and the presence or absence of
      functional Rb protein (reported previously) in the cell lines were compared.
      RESULTS: Homozygous deletion of CDKN2 was detected in 18 (23%) of 77 cell lines
      established from patients with NSCLC, compared with one (1%) of 93 cell lines
      established from patients with SCLC (P < .001). No CDKN2 gene loss was observed
      in the normal tissue of an NSCLC patient whose tumor cell line showed homozygous
      deletion of the gene; however, the primary tumor from this patient had evidence
      of CDKN2 loss. Homozygous CDKN2 deletion was detected in 13 (28%) of 46 tumor
      cell lines from patients with stage III or stage IV NSCLC, compared with zero of
      10 tumor cell lines from patients with stage I or stage II NSCLC. Coincident loss
      of CDKN2 genes and functional Rb protein was rarely observed (in two of 135 cell
      lines). CONCLUSION: The frequency of homozygous CDKN2 gene deletion in NSCLC cell
      lines is greater than that observed for any other known, or candidate, tumor
      suppressor gene. IMPLICATION: Further study of the role of CDKN2 gene alteration
      in the pathogenesis of NSCLC is needed.

PMID- 7563156
TI  - Re: Prophylactic cranial irradiation for patients with small-cell lung cancer.

PMID- 7563157
TI  - Re: Prophylactic cranial irradiation for patients with small-cell lung cancer.

PMID- 7563159
TI  - Screening women aged 40-49 years: where are we today?

PMID- 7563158
TI  - A question that will not go away: at what age should mammographic screening
      begin?

PMID- 7563160
TI  - Importance of chromosome 9p loss in human lung cancer.

PMID- 7563161
TI  - Managed care forces cancer centers to retrench.

PMID- 7563162
TI  - Elusive estrogens may hold key to some cancer risk.

PMID- 7563163
TI  - Hormones influence on cancers still foggy.

PMID- 7563164
TI  - Cancer survival varies widely across Europe, new study finds.

PMID- 7563166
TI  - New drug screen assay uses fewer mice, while cutting costs.

PMID- 7563165
TI  - Better access for the poor may improve lung cancer survival.

PMID- 7563167
TI  - Quantitative interpretation of age-specific mortality reductions from the Swedish
      breast cancer-screening trials.
AB  - BACKGROUND: Results from five Swedish randomized trials may provide the most
      conclusive evidence on the effect of mammographic screening and have been used to
      forecast the expected reduction in breast cancer mortality in other programs.
      However, those trials demonstrated different degrees of reduction. The
      interpretation of observed mortality reduction after long follow-up for women
      aged 40-49 years at trial entry is both important and controversial. PURPOSE: We
      estimated what percentage of the observed mortality reduction for women aged 40
      49 years at entry into the five Swedish screening trials might be attributable to
      screening these women at 50 years of age or older. Moreover, we calculated the
      most likely percentage mortality reduction for specific screening programs if the
      Swedish results were generalized and analyzed whether characteristics of each
      trial might at least partly explain the observed differences in reductions among
      the trials. METHODS: Each Swedish trial was simulated with one underlying
      computer simulation model (MISCAN--MIcrosimulation SCreening ANalysis) of the
      natural history of the disease and the performance of screening, taking into
      account nine important trial characteristics. Improvement in prognosis for screen
      detected case patients was estimated with age-specific reduction for all trials
      and each trial design as a reference. RESULTS: An expected 7% reduction in breast
      cancer mortality for women aged 40-49 years at trial entry (relative risk [RR] =
      0.93) was determined by computer modeling, assuming no improvement in prognosis
      for cancers that are screen detected before 50 years of age. This result
      indicates that, of the overall 10% observed reduction (RR = 0.90) in the five
      Swedish trials analyzed, most (70%) of this reduction might be attributable to
      screening these women in later rounds after their 50th birthday. Using additional
      trial information, predictions of breast cancer mortality reduction in women 50
      years or older might be 11% larger than previously expected, assuming that high
      quality mammographic screening can be achieved in nationwide programs. For women
      aged 50-69 years at trial entry, the differences in expected versus observed
      mortality reduction among the trials are estimated to be relatively small.
      (Expected mortality reductions range from 24% to 32%). CONCLUSIONS: Results from
      the Swedish randomized breast cancer-screening trials should be seen as more
      favorable regarding the effect of mammographic screening in reducing breast
      cancer mortality for women aged 50-69 years than was estimated earlier. Our
      analyses also suggest that the improvement in prognosis due to screening for
      women aged 40-49 years is much smaller than that for women aged 50 years or
      older. Approximately, 70% of the 10% observed reduction in breast cancer
      mortality (i.e., 7%) for women aged 40-49 years at trial entry might be
      attributable to a reduction due to screening these women after they reach age 50.
      IMPLICATIONS: Detailed screening data for the 40- to 49-year age group of all
      Swedish trials should be analyzed to specifically estimate the natural history
      and performance of screening in this age group.

PMID- 7563168
TI  - Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying
      non-small-cell lung cancers.
AB  - BACKGROUND: Carcinogenesis is a multistep process, which may begin as a
      consequence of chromosomal changes. Deletions in the short arm of chromosome 9
      (9p) have been observed in lung carcinomas. In addition, morphologically
      recognizable preneoplastic lesions, frequently multiple in number, precede onset
      of invasive carcinomas. PURPOSE: We tested for deletions and loss of
      heterozygosity (LOH) at 9p loci in preneoplastic and neoplastic foci in lungs of
      patients with non-small-cell lung carcinomas (NSCLCs). METHODS: Seven archival,
      paraffin-embedded, surgically resected NSCLC specimens were selected. They were
      predominantly from patients with adenocarcinomas and contained multiple
      preneoplastic lesions, including hyperplasia, metaplasia, dysplasia, and
      carcinoma in situ (CIS). Fifty-three histologically identified preneoplastic and
      malignant lesions present in bronchi, bronchioles, and alveoli were precisely
      microdissected from stained tissue sections with a micromanipulator. Stromal
      lymphocytes were used to determine constitutional heterozygosity. The specimens
      were analyzed for LOH using polymerase chain reaction-based assays for
      polymorphism in dinucleotide repeats (microsatellite markers) in interferon alfa
      (IFNA) and D9S171 loci on 9p. RESULTS: All seven cases were constitutionally
      heterozygous for one or both microsatellite markers. Five of seven cases had LOH
      at one or both 9p loci in the invasive primary cancers (doubly informative
      cases). Four of these five cases also revealed LOH in preneoplastic foci. In the
      doubly informative cases, LOH was detected in five (38%) of 13 foci of
      hyperplasia, four (80%) of five foci of dysplasia, and three (100%) of three CIS
      lesions. LOH was detected in preneoplastic lesions from all regions of the
      respiratory tract, including bronchi, bronchioles, and alveoli, and involved five
      different cell types. The identical allele was lost from both the preneoplastic
      lesions and the corresponding tumors (12 of 12 lesions, 17 of 17 comparisons), a
      phenomenon we have referred to as "allele-specific mutation." Statistical
      analyses employing a cumulative binomial test demonstrated that the probabilities
      of such findings occurring by chance are 2.4 x 10(-4) and 7.6 x 10(-6),
      respectively. From comparisons with the previously published data on other
      chromosomal abnormalities in the same tissue specimens, it appears that LOH at 3p
      and 9p loci occurred early in the hyperplasia stage, but the ras gene point
      mutations were relatively late, at the CIS stage. CONCLUSIONS: LOH at 9p loci
      occurs at the earliest stage in the pathogenesis of lung cancer and involves all
      regions of the respiratory tract. LOH in NSCLC is not random but targets a
      specific allele in individuals. Studying preneoplastic lesions may help identify
      intermediate markers for risk assessment and chemoprevention.

PMID- 7563169
TI  - Drug resistance-associated marker Lrp for prediction of response to chemotherapy
      and prognoses in advanced ovarian carcinoma.
AB  - BACKGROUND: Drug resistance is a major impediment to the successful treatment of
      ovarian carcinoma. None of the earlier-identified resistance mechanisms, such as
      overexpression of the MDR1 gene product, P-glycoprotein (Pgp), has been shown to
      be a major determinant of clinical response to chemotherapy and survival for
      ovarian cancer patients. The multidrug resistance-associated protein (Mrp) and
      the lung resistance protein (Lrp, also called the p110 major vault protein), are
      newly described proteins associated with multidrug resistance in vitro. PURPOSE:
      The aim of this retrospective study was to investigate the expression of Mrp and
      Lrp, in addition to Pgp, in advanced ovarian carcinoma and to determine whether
      such expression was predictive of response to chemotherapy and survival. METHODS:
      Fifty-seven banked frozen specimens, previously collected and frozen at the time
      of diagnosis from an equal number of patients with International Federation of
      Gynecology and Obstetrics (FIGO) stage III or IV ovarian carcinoma, were
      immunostained for Pgp (with monoclonal antibodies [MAbs] MRK-16 and JSB-1), Mrp
      (with MAb MRPrl), and Lrp (with MAb LRP-56). All patients had received platinum-
      or alkylating-based chemotherapy after debulking surgery. Clinicopathologic
      parameters determined at diagnosis were retrospectively assessed for their
      relationship with Pgp, Mrp, and Lrp expression. Response to treatment and
      survival were compared between Pgp, Mrp, and Lrp expression groups. Qualitative
      variables were analyzed using Fisher's exact test or the chi-squared test. All
      reported P values are two-tailed. RESULTS: Nine (16%), 39 (68%), and 44 (77%) of
      the 57 tumor specimens examined showed positive immunostaining for Pgp, Mrp, and
      Lrp, respectively. Positive immunostaining for these proteins was not associated
      with any other prognostic factor examined. No association was found between Pgp
      and Mrp expression and response to chemotherapy and survival. In contrast,
      patients with Lrp-positive tumors had poorer response to chemotherapy (P = .004)
      and shorter progression-free (P = .003) and overall (P = .007) survival than Lrp
      negative patients. Multivariate analysis of Lrp expression, FIGO stage, residual
      tumor after initial surgery, tumor grade, and presence or absence of ascites
      showed that only Lrp status was independently related to both progression-free
      survival and overall survival. CONCLUSIONS: Positive Lrp immunostaining in
      advanced ovarian carcinoma appears to be an indicator of poor response to
      standard chemotherapy (platinum or alkylating agents) and of adverse prognoses.
      IMPLICATIONS: The functional characterization of Lrp and related proteins may
      reveal new approaches to modulate Lrp-associated drug resistance. A large
      prospective study is warranted to confirm the prognostic value of Lrp.

PMID- 7563170
TI  - Vascular permeability factor (vascular endothelial growth factor) expression and
      angiogenesis in cervical neoplasia.
AB  - BACKGROUND: Angiogenesis is a critical factor in the progression of solid tumors,
      including cervical cancers. The mechanisms responsible for angiogenesis in
      cervical neoplasia, however, are not well defined. PURPOSE: Our goal was to
      determine the relationship between angiogenesis and the expression of the
      angiogenic cytokine vascular permeability factor (VPF), also known as vascular
      endothelial growth factor, and its receptors in cervical neoplasia. METHODS:
      Sixty-six cervical biopsy specimens were evaluated; among these, 16 samples were
      designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as
      high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell
      carcinomas. Histologic sections immunostained for factor VIII-related antigen
      were evaluated quantitatively for microvessel density and for the presence of
      epithelial-stromal vascular cuffing. Sections were also evaluated for VPF
      messenger RNA (mRNA) expression by in situ hybridization. RESULTS: VPF mRNA
      expression, epithelial-stromal vascular cuffing, and microvessel density counts
      were significantly increased in invasive carcinoma and in high-grade
      intraepithelial lesions as compared with low-grade intraepithelial lesions and
      benign squamous epithelium. Vascular cuffing and increased microvessel density
      counts were also significantly associated with increased VPF mRNA expression.
      CONCLUSIONS: These observations suggest that VPF is an important angiogenic
      factor in cervical neoplasia.

PMID- 7563171
TI  - Polymorphism of glutathione S-transferase M1 and lung cancer risk among African
      Americans and Caucasians in Los Angeles County, California.
AB  - BACKGROUND: Glutathione S-transferase M1 (GSTM1) is active in the detoxication of
      a number of carcinogens, including polyaromatic hydrocarbons, such as those
      present in cigarette smoke. In about 30%-55% of individuals, depending on the
      ethnic group, there is a virtual absence of GSTM1 enzyme activity due to deletion
      of both copies of the GSTM1 gene (GSTM1 null genotype). This genetic polymorphism
      of the GSTM1 gene locus has been proposed as a risk factor for lung cancer.
      However, results across studies are inconsistent. PURPOSE: We conducted a case
      control study of patients with incident lung cancer and population control
      subjects to examine the association between homozygous deletion of the GSTM1 gene
      and lung cancer risk among African-Americans and Caucasians. METHODS: At 35
      hospitals in Los Angeles County, California, we identified patients with a first
      diagnosis of lung cancer between September 1, 1990, and January 6, 1994. Of the
      859 potentially eligible case patients, 207 had died by the time their physicians
      had received our request for permission to contact them. We enrolled 356 eligible
      case patients (167 African-Americans and 189 Caucasians) and 731 eligible control
      subjects (258 African-Americans and 473 Caucasians, all residents of Los Angeles
      County). Samples of white blood cell DNA sufficient for determination of the
      GSTM1 genotype by a polymerase chain reaction-based assay were obtained from 342
      case patients and 716 control subjects. The odds ratios (ORs) and 95% confidence
      intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1
      gene, in total and after stratification by a number of relevant characteristics,
      were estimated by logistic regression analysis. RESULTS: For patients with all
      lung cancers combined, the GSTM1 null genotype was associated with an OR of 1.29
      (95% CI = 0.94-1.77). The OR was similar among African-Americans (OR = 1.20; 95%
      CI = 0.72-2.00) and Caucasians (OR = 1.37; 95% CI = 0.91-2.06). The association
      was strongest for squamous cell carcinoma (OR = 1.57; 95% CI = 0.93-2.63). We
      observed an OR of 1.77 (95% CI = 1.11-2.82) for the GSTM1 null genotype in
      relation to lung cancer risk among smokers of less than 40 pack-years, but no
      association among heavier smokers (OR = 0.90; 95% CI = 0.56-1.44). CONCLUSIONS:
      Our data do not support a substantial association between homozygous deletion of
      the GSTM1 gene and the risk of lung cancer overall in this population. However,
      our data do suggest an elevated risk for lighter smokers with this genotype.
      IMPLICATIONS: Because the power of our analyses within strata of lifetime smoking
      history was limited, larger studies will be needed to confirm these findings.

PMID- 7563172
TI  - Accumulation of p53 protein as a possible predictor of response to adjuvant
      combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and
      prednisone for breast cancer.

PMID- 7563175
TI  - Survival without tumor shrinkage: re-evaluation of survival gain by cytostatic
      effect of chemotherapy.

PMID- 7563173
TI  - Expression pattern of MRP in human tissues and adult solid tumor cell lines.

PMID- 7563174
TI  - Inhibition of mammary carcinogenesis in rats by sulfone metabolite of sulindac.

PMID- 7563176
TI  - Mammography screening.

PMID- 7563177
TI  - Cell cycle and cancer.

PMID- 7563178
TI  - Smoking, treatment for Hodgkin's disease, and subsequent lung cancer risk.

PMID- 7563179
TI  - Researchers gain footholds in the cell cycle.

PMID- 7563180
TI  - BRCA1 alteration found in eastern European Jews.

PMID- 7563181
TI  - Screening tests pick up too many indolent cancers.

PMID- 7563182
TI  - IARC director juggles agency's public health mission with cutting-edge research.

PMID- 7563183
TI  - NCI survey explores the M.D.'s perspective on ABMT trials.

PMID- 7563184
TI  - Congressional legislation will affect cancer research.

PMID- 7563185
TI  - RET gene and its implications for cancer.
AB  - The RET proto-oncogene encodes a protein receptor tyrosine kinase. RET mutations
      are associated with the dominantly inherited cancer syndromes multiple endocrine
      neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma (FMTC).
      In MEN 2A, MEN 2B, and FMTC, direct detection of RET mutations can be used to
      identify disease allele carriers prior to the development of clinically evident
      neoplasms. RET mutations are also associated with sporadic thyroid carcinomas.
      The effects of RET mutation on protein function have been investigated both in
      vivo and in vitro, and the study of RET has served to provide insights into the
      mechanisms of tumorigenesis in general.

PMID- 7563186
TI  - Deletion of the p16 and p15 genes in human bladder tumors.
AB  - BACKGROUND: Two genes, p16 (also known as CDKN2, INK4A, or MTS1) and p15 (also
      described as INK4B or MTS2), are found in tandem at chromosome 9p21. These genes
      are designated as candidate tumor suppressor genes because they encode proteins
      that function as negative cell cycle regulators. (The encoded polypeptides
      inactivate specific cyclin-protein kinase complexes that are required for
      progression through the cell cycle.) Molecular genetic studies have revealed that
      deletion of the p16 and p15 genes occurs frequently in cancer cell lines and in
      certain malignant neoplasms. PURPOSE: We evaluated the frequency of p16 and p15
      gene alterations in a well-characterized cohort of human transitional cell
      bladder cancers, and we explored potential associations between alterations in
      these genes and tumor stage and/or grade. METHODS: Tumor tissue and normal tissue
      from 110 patients with transitional cell carcinoma of the urinary bladder were
      examined. The status of the p16 and p15 genes in these tissues was determined by
      Southern blotting and hybridization with gene-specific probes, by coupled
      polymerase chain reaction and single-strand conformation polymorphism analysis
      (PCR-SSCP), and by sequencing DNA fragments produced during PCR. Associations
      between alterations in the genes and tumor stage and/or grade were evaluated
      using the two-tailed Fisher's exact test. RESULTS: Homozygous deletion (both
      alleles lost) of the p16 and the p15 genes was observed in 11 and nine bladder
      tumors, respectively. Eight of the 11 tumors exhibiting complete loss of the p16
      gene also displayed homozygous deletion of the p15 gene. Exclusive loss of either
      gene was detected in only three tumors. Hemizygous deletion (one allele lost,
      also referred to as loss of heterozygosity [LOH] of the p16 and/or p15 genes was
      observed in eight tumors. Rearrangement of the two genes was indicated in three
      additional tumors. No point mutations were identified in either gene. The overall
      frequency of alteration in this cohort of bladder tumors was approximately 18%
      for each gene (in 20 [18.3%, 95% confidence interval (CI) = 11.1%-25.6%] of 109
      informative tumors for the p16 gene and in 18 [18%, 95% CI = 10.5%-25.5%] of 100
      informative tumors for the p15 gene). A statistically significant association
      between p16 gene alteration and bladder tumors of low stage (P < .01) and grade
      (P < .01) was observed; a significant association between p15 gene alteration and
      tumors of low stage (P < .01) was also detected. CONCLUSIONS: Alteration of the
      p16 and p15 genes, especially coincident homozygous deletion, appears to be a
      common event in bladder cancer.

PMID- 7563188
TI  - Influence of tobacco marketing and exposure to smokers on adolescent
      susceptibility to smoking.
AB  - BACKGROUND: Today the uptake of smoking is primarily an adolescent pursuit.
      Awareness of tobacco advertising and promotion is high, and evidence suggests
      that it plays a role in adolescent smoking uptake. PURPOSE: We evaluated the
      influence of tobacco advertising and promotion and exposure to smokers on never
      smoking adolescents' susceptibility to smoking. METHODS: We used data on 3536
      adolescent never smokers (those who had never even puffed on a cigarette) from
      the 1993 California Tobacco Survey. That survey questioned adolescents about
      smoking history and inclinations. For this analysis, we defined as susceptible to
      smoking those never smokers who said on the survey that they could not rule out
      independently deciding to try a cigarette soon or smoking one offered by a
      friend. Also for this analysis, we devised two indices: 1) a 5-point index of an
      individual's receptivity to tobacco advertising as determined by the number of
      positive responses to five survey items (recognition of advertising messages,
      having a favorite advertisement, naming a brand he/she might buy, owning a
      tobacco-related promotional item, and willingness to use a tobacco-related
      promotional item) and 2) an index classifying an individual's reported exposure
      to family and peer smoking into one of four levels. Using logistic regression, we
      assessed the independent importance of our indices in predicting susceptibility
      to smoking after adjustment for sociodemographic variables, including age, sex,
      and race/ethnicity, and for perceived school performance. Tests of statistical
      significance were two-sided. RESULTS: Receptivity to tobacco advertising and
      exposure to smokers were independently associated with susceptibility to smoking,
      but the relationship appeared stronger for receptivity to advertising.
      Adolescents exposed to family members and peers (n = 489) who smoked were 1.89
      (95% confidence interval [CI] = 1.30-2.74) times as likely to be susceptible,
      whereas adolescents who scored 4 or more on the Index of Receptivity to Tobacco
      Marketing (n = 361) were 3.91 (95% CI = 2.38-6.42) times as likely to be
      susceptible as those who scored 0. Even adolescents who scored 2 (n = 1090) were
      2.03 (95% CI = 1.31-3.15) times as likely to be susceptible. There was no
      interaction effect between score on the Index of Receptivity to Tobacco Marketing
      and exposure to smokers. CONCLUSION: Our results support the hypothesis that
      tobacco marketing may be a stronger current influence in encouraging adolescents
      to initiate the smoking uptake process than exposure to peer or family smokers or
      sociodemographic variables including perceived school performance.

PMID- 7563187
TI  - Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease.
AB  - BACKGROUND: Several studies have shown that survivors of Hodgkin's disease have
      increased risk of lung cancer, but the factors responsible for this excess risk
      are not well known. PURPOSE: This study was undertaken to investigate the effects
      of radiation dose, chemotherapy, and smoking on the risk of lung cancer following
      treatment of Hodgkin's disease. METHODS: We conducted a case-control study in a
      cohort of 1939 patients treated for Hodgkin's disease from 1966 through 1986 in
      The Netherlands. Detailed treatment information was collected from the medical
      records for 30 case patients with lung cancer following Hodgkin's disease and 82
      matched control subjects who had not developed lung cancer. Multiple sources were
      used to obtain as complete smoking histories of the study participants as
      possible. For each case-control set, the radiation dose received by the area of
      the lung where the case patient developed the tumor was estimated on the basis of
      radiotherapy charts and experimental simulations of treatments. The estimates of
      relative risk (RR) for lung cancer associated with specific exposures were
      obtained from logistic regression methods, and all tests of statistical
      significance were two-sided. RESULTS: A statistically significant increase in
      risk of lung cancer was observed with increasing radiation dose (P for trend =
      .01) with an RR of 9.6 (95% confidence interval [CI] = 0.93-98) for patients who
      received 9 Gy or more compared with those who received less than 1 Gy. Patients
      who smoked more than 10 pack-years after the diagnosis of Hodgkin's disease had a
      sixfold increase in the risk of lung cancer compared with patients who smoked
      less than 1 pack-year (P = .03). Positive interaction on a multiplicative scale
      was observed between the carcinogenic effects of smoking and radiation. The
      increase in risk of lung cancer with increasing radiation dose was much greater
      among the patients who smoked after diagnosis of Hodgkin's disease than among
      those who refrained from smoking (P = .04). There was no increase in lung cancer
      risk in relation to the number of cycles of chemotherapy or the cumulative doses
      of the drugs mechlorethamine and procarbazine. CONCLUSIONS: The excess risk of
      lung cancer in Hodgkin's disease patients treated with radiotherapy is related to
      the radiation dose received by the affected area of the lung. Smokers experience
      a significantly greater risk attributable to radiotherapy than nonsmokers.
      IMPLICATIONS: Physicians in charge of patient treatment should make a special
      effort to dissuade Hodgkin's disease patients from smoking after receiving
      radiotherapy.

PMID- 7563189
TI  - Effect of matrix metalloproteinase inhibitor batimastat on breast cancer regrowth
      and metastasis in athymic mice.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the invasion and
      metastasis of human cancers by mediating the degradation of extracellular matrix
      components. Therefore, these enzymes constitute promising targets in the
      development of anticancer therapies. Batimastat ([(4-N-hydroxyamino)-2R-isobutyl
      3S-(thienyl-thiomethyl)succinyl]-L- phenyl-alanine-N-methylamide) is one of a new
      class of agents designed to inhibit MMP activity. PURPOSE: We asked whether
      batimastat, given as adjuvant therapy after primary tumor resection, could
      inhibit local-regional tumor regrowth and the formation of lung metastases in a
      human breast cancer xenograft model. We also explored possible effects of
      batimastat on breast cancer cell viability and on the accumulation of specific
      messenger RNAs (mRNAs). METHODS: Human MDA-MB-435 breast cancer cells were
      treated in vitro for 6 days with batimastat at concentrations ranging from 0.1 to
      10.0 microM, and then viable cell counts were performed. The activity of
      collagenases, directly associated with cultured MDA-MB-435 cells or released into
      their culture fluids, was assessed by gelatin zymography after 1 and 3 days of
      batimastat treatment (drug range, 0.2-2.0 microM). Athymic nude mice were given
      daily intraperitoneal injections of batimastat (30 mg/kg body weight) after
      resection of MDA-MB-435 primary tumors grown in their mammary fat pads; the
      volumes of tumor regrowths and the numbers and volumes of lung metastases were
      calculated; neovascularization in the regrowths was assessed by
      immunohistochemical analysis with an antibody directed against CD31, an
      endothelial cell antigen. The effect of batimastat treatment on the accumulation
      of mRNAs encoding specific MMPs and the tissue inhibitor of metalloproteinases-2
      (TIMP-2) in cultured cells, primary tumors, and tumor regrowths was measured by
      RNA dot blotting and hybridization with complementary probes. Linear regression
      analysis, Student's t tests, and chi-squared analysis were used to evaluate the
      data. RESULTS: The viability of cultured MDA-MB-435 cells was not affected by
      treatment with batimastat; however, measured activities for the 72-kd and 92-kd
      collagenases released by these cells were reduced after batimastat treatment.
      Intraperitoneal injection of batimastat significantly inhibited the local
      regional regrowth of resected MDA-MB-435 tumors in athymic nude mice (in
      comparison with control mice, P = .035), and it reduced the incidence (P < .05),
      number (P = .0001), and total volume (P = .0001) of lung metastases. Batimastat
      treatment did not affect cellular levels of MMP or TIMP-2 mRNAs. CONCLUSION:
      Batimastat inhibits human breast cancer regrowth and metastasis in a nude mouse
      xenograft model. Potential mechanisms for batimastat's inhibitory activity do not
      include direct cell toxicity or alteration of MMP or TIMP mRNA levels.

PMID- 7563190
TI  - Educational attainment and racial differences in cigarette smoking.

PMID- 7563191
TI  - Lack of vesicant injury following extravasation of liposomal doxorubicin.

PMID- 7563192
TI  - Re: Potential impact of genetic testing on cancer prevention trials, using breast
      cancer as an example.

PMID- 7563193
TI  - Fluorouracil: active in ZD1694 (tomudex)-resistant cell lines with markedly
      elevated thymidylate synthase levels.

PMID- 7563194
TI  - Protein N-myristoylation as a chemotherapeutic target for cancer.

PMID- 7563195
TI  - Chemosensitizers to overcome and prevent multidrug resistance?

PMID- 7563196
TI  - Cultural gaps leave patients angry, doctors confused.

PMID- 7563197
TI  - BRCA1 discovery aftermath: no rush for genetic testing.

PMID- 7563198
TI  - Gallo retires from NIH to launch new research facility.

PMID- 7563200
TI  - Nocturnal animals help shed light on human melanoma.

PMID- 7563199
TI  - Polymers help guide cancer drugs to tumor targets--and keep them there.

PMID- 7563201
TI  - Modulation of the organ microenvironment for treatment of cancer metastasis.

PMID- 7563202
TI  - Decreased mutation rate for cellular resistance to doxorubicin and suppression of
      mdr1 gene activation by the cyclosporin PSC 833.
AB  - BACKGROUND: Various mechanisms can contribute to cellular resistance to
      doxorubicin. These include expression of the multidrug transporter P-glycoprotein
      (product of the mdr1 gene [also known as PGY1], Mrp (multidrug resistance
      associated protein), the p110 major vault protein, altered glutathione
      metabolism, and altered levels or activity of topoisomerase II (Topo II). We
      reported recently that single-step treatment of human MES-SA sarcoma cells with
      40 nM doxorubicin resulted in selection of spontaneous mutants at a rate of 1.8 x
      10(-6) per cell generation. All individually selected mutants manifested the
      multidrug-resistant phenotype, related to activation of the mdr1 gene. PURPOSE:
      Luria and Delbruck fluctuation analysis was performed with MES-SA cells to
      determine the mutation rate and the nature and mechanisms of resistance after
      single-step selection with doxorubicin in the presence of the cyclosporin PSC
      833, a potent modulator of multidrug resistance. METHODS: Ten flasks were seeded
      with 2000 cells/flask and grown to confluent populations of approximately 8 x
      10(6) cells. After reseeding in 96-well plates, the populations were treated with
      40 nM doxorubicin and 2 microM PSC 833 for 3 weeks. Surviving colonies were
      scored, individually harvested, and propagated. The drug-resistant phenotype was
      assessed by the tetrazolium dye (MTT) cytotoxicity assay and by monitoring
      cellular glutathione content and radiolabeled drug accumulation. Coupled reverse
      transcription-polymerase chain reaction (RT-PCR) was used to evaluate mdr1, MRP,
      Topo II alpha, and Topo II beta gene expression. Topo II, P-glycoprotein, and
      p110 levels were examined by immunoblotting or immunocytochemistry. Topo II
      activity was assessed by decatenation of kinetoplast DNA, and etoposide-induced
      cleavable complex formation was studied by the potassium-sodium dodecyl sulfate
      precipitation assay. RESULTS: Mutations were detected at a rate of 2.5 x 10(-7)
      per cell generation. Analysis of variance indicates that spontaneous mutations,
      rather than changes in cellular function, conferred resistance to doxorubicin and
      PSC 833. None of the isolated clones expressed mdr1 messenger RNA or P
      glycoprotein, and none exhibited an increase in MRP expression. No alterations
      were found in cellular glutathione content, intracellular accumulations of
      daunorubicin and etoposide, levels of p110 protein, or levels of Topo II beta
      transcripts. However, a significant decrease in Topo II alpha messenger RNA and
      protein was found in all examined clones, as well as decreased Topo II catalytic
      activity and reduced cleavable complex formation in the presence of etoposide.
      CONCLUSIONS: PSC 833 co-selection reduced the mutation rate for doxorubicin
      selected resistance by 10-fold and suppressed the emergence of mdr1 mutants.
      Survival of cells exposed to doxorubicin and PSC 833 occurs by selection of
      spontaneously arising mutants that exhibit altered Topo II alpha expression.
      IMPLICATIONS: Our results suggest that treatment with multidrug resistance
      modulators such as PSC 833 together with multidrug resistance-related cytotoxins
      may suppress the activation of mdr1 and prevent the emergence of resistant cancer
      cell clones with the multidrug-resistant phenotype.

PMID- 7563203
TI  - Angiogenesis in bladder cancer: relationship between microvessel density and
      tumor prognosis.
AB  - BACKGROUND: Tumor stage, histologic grade, and regional lymph node status are
      currently used to obtain prognostic information about bladder cancers. However,
      additional prognostic indicators are needed to aid clinicians in selecting
      patients who would benefit most from specific therapies. A majority of studies
      assessing the prognostic value of measuring tumor angiogenesis (i.e., measurement
      of tumor microvessel densities) have found a positive association between
      increasing microvessel densities and worsening prognosis. PURPOSE: We explored
      the relationship between established prognostic indicators and the extent of
      tumor-associated angiogenesis in patients with invasive transitional cell
      carcinoma (TCC) of the bladder, and we determined whether tumor microvessel
      density measurement could be used independently to predict bladder tumor
      behavior. METHODS: Tumor tissue was obtained from 164 patients with invasive
      primary TCC of the bladder. The extent of tumor-associated angiogenesis in this
      tissue was evaluated by immunohistochemical methods using HPCA-1, a mouse
      monoclonal antibody directed against the endothelial cell antigen, CD34. The
      number of microvessels in a 200x microscopic high-power field (hpf) containing
      the area of greatest neovascularization within or immediately adjacent to each
      tumor was determined. The patient population was then divided into three
      equivalently sized groups, with tumors containing low (< or = 64), intermediate
      (65-99), or high (> or = 100) numbers of microvessels per hpf. Kaplan-Meier
      product limit estimates of overall survival and the complement of cumulative
      incidence curves for recurrence-free survival were plotted. When analyzing
      survival or recurrence, the logrank test was used to compare groups of patients
      with and without stratification according to tumor stage. Analysis of variance
      was used to test for an association between microvessel density and established
      prognostic variables. Reported P values are from two-sided tests. RESULTS:
      Microvessel density was significantly associated with disease-free (P < .0001)
      and overall (P = .0007) survival. The estimated probabilities of recurrence at 5
      years were 19% (95% confidence interval [CI] = 8-29), 56% (95% CI = 43-69), and
      68% (95% CI = 55-81) for patients with lowest, intermediate, and highest
      microvessel counts, respectively. Overall survival at 5 years was estimated to be
      68% (95% CI = 56-81), 44% (95% CI = 30-57), and 34% (95% CI = 21-47) for the same
      three patient groups. Microvessel density was associated with disease progression
      in patients with organ-confined tumors, tumors extending through the bladder
      wall, and tumors that had spread to regional lymph nodes. Tumor angiogenesis was
      found to be an independent prognostic indicator when evaluated in the presence of
      histologic grade, pathologic stage, and regional lymph node status. CONCLUSION:
      Tumor angiogenesis, as determined by microvessel density measurement, is an
      independent prognostic indicator for patients with invasive TCC of the bladder.

PMID- 7563204
TI  - Medical diagnostic x rays and thyroid cancer.
AB  - BACKGROUND: Diagnostic x rays are the largest man-made source of exposure to
      ionizing radiation for the general population. Whether there are meaningful
      cancer risks associated with such exposures is unclear. Most previous case
      control studies have relied on recalled histories of x rays, and there is concern
      that completeness and accuracy of recall might differ between cancer case and
      control subjects. PURPOSE: The present study used information recorded
      prospectively in hospital charts to address the relationship between medical
      diagnostic x rays and risk of thyroid cancer. METHODS: The Swedish Cancer
      Registry and the Uppsala-Orebro Regional Cancer Registry were used to identify
      persons with papillary or follicular thyroid cancer diagnosed from January 1,
      1980, through December 31, 1992, among residents of the Uppsala Health Care
      Region. After histopathologic review, there were 484 such case subjects available
      for study. An equal number of age-, sex-, and county of residence-matched control
      subjects from the general population were randomly selected on the basis of the
      Swedish Registry of the Total Population. Lifetime residential histories were
      compiled, and radiology records were searched at all Swedish hospital serving
      regions where study subjects ever maintained an official residence. Approximate
      radiation doses to the thyroid gland for specific types of x-ray examinations
      were assigned on the basis of mean values of measurements made in Sweden in 1973
      1975 and in the United States in 1970. Odds ratios were used to evaluate the
      association between diagnostic radiography and risk of thyroid cancer. RESULTS: A
      total of 3853 medical diagnostic x rays were ascertained among thyroid cancer
      case subjects and 4039 among the matched control subjects. There were no tendency
      for case subjects to have had more of the types of x-ray procedure associated
      with higher radiation dose to the thyroid gland (i.e., those involving the head
      or neck area). This finding was true even when analysis was restricted to x rays
      occurring before 1960, when doses likely were higher than in more recent years,
      and for examinations occurring in childhood and adolescence, when susceptibility
      to radiation-induced thyroid cancer is greatest. The relative risk of thyroid
      cancer was not significantly associated with estimated cumulative dose to the
      thyroid gland from diagnostic x rays (two-sided P for trend = .80). CONCLUSION:
      These data indicate that the risk of thyroid cancer due to medical diagnostic x
      rays, if any, is very small.

PMID- 7563205
TI  - Mammographic features and breast cancer risk: effects with time, age, and
      menopause status.
AB  - BACKGROUND: Mammographic images from women with a high proportion of epithelial
      and stromal breast tissues are described as showing high-density parenchymal
      patterns. Most past studies that noted an increase in breast cancer risk
      associated with mammographic parenchymal patterns showing high density either 1)
      lacked information on other breast cancer risk factors, 2) were too small, or 3)
      included insufficient follow-up time to adequately resolve persisting doubts
      whether mammographic features are "independent" measures of breast cancer risk
      and not a detection artifact. PURPOSE: The purpose of this study was twofold: 1)
      to evaluate the associations between mammographic features and other breast
      cancer risk factors and 2) to assess effects of mammographic features on breast
      cancer risk by time, age, and menopause status. METHODS: To address these
      questions, we analyzed detailed information from a large, nested case-control
      study with 16 years of follow-up. This study used information from both screening
      and follow-up phases of the Breast Cancer Detection Demonstration Project, a
      nationwide program that offered annual breast cancer screening for more than
      280,000 women from 1973 to 1980. Mammographic features were assessed from the
      base-line screening mammographic examination for 1880 incident case subjects and
      2152 control subjects. Control subjects were randomly selected from women of the
      same age and race as each case subject. Control subjects attended the same
      screening center as the case subject and were free of breast cancer at the case
      subject's date of diagnosis. Odds ratios (ORs) with 95% confidence intervals
      (CIs) provided estimates of the relative risk of breast cancer. RESULTS:
      Mammographic features were associated with known breast cancer risk factors.
      However, the high-density parenchymal pattern effects were independent of family
      history, age at first birth, alcohol consumption, and benign breast disease. The
      increase risk for women with Wolfe's two high-density parenchymal patterns, P2
      (OR = 3.2; 95% CI = 2.5-4.0) and Dy (OR = 2.9; 95% CI = 2.2-3.9), was explained
      primarily by measured percent of the breast with dense mammographic appearance.
      Compared with women with no visible breast density, women who had a breast
      density of 75% or greater had an almost fivefold increased risk of breast cancer
      (95% CI = 3.6-7.1). These effects persisted for 10 or more years and were noted
      for both premenopausal and postmenopausal women of all ages. CONCLUSIONS: Of the
      breast cancer risk factors assessed in the participants, high-density
      mammographic parenchymal patterns, as measured by the proportion of breast area
      composed of epithelial and stromal tissue, had the greatest impact on breast
      cancer risk. Of the breast cancers in this study, 28% were attributable to having
      50% or greater breast density.

PMID- 7563206
TI  - Increased N-myristoyltransferase activity observed in rat and human colonic
      tumors.
AB  - BACKGROUND: Colorectal cancer is one of the leading causes of cancer death in
      North America. Since treatment of colonic cancer remains difficult because of the
      lack of effective chemotherapeutic agents, it is important to continue to search
      for cellular functions that can be disrupted by chemotherapeutic drugs and
      inhibit the development or progression of this disease. Modification of proteins
      by myristoylation has been recognized as important in the function of various
      viral, oncogenic, and signal-transduction proteins and thus has been proposed as
      a target for chemotherapeutic drug design. However, the activity of the enzyme
      that catalyzes this modification, N-myristoyltransferase, has not been
      investigated in cancer relative to normal tissue. PURPOSE: The purpose of this
      study was twofold: 1) to investigate the activity of N-myristoyltransferase in
      azoxymethane-induced rat colonic cancer tissue compared with normal and normal
      appearing rat colonic tissue and 2) to determine if similar differences would be
      observed in a small sample of human colonic tumors. METHODS: N
      Myristoyltransferase activity was determined in 45 colonic tissue specimens from
      Sprague-Dawley rats--10 given injections of the colon carcinogen, azoxymethane,
      and three untreated. Tissue specimens included 35 colonic tumors of varying
      pathologic stages, seven specimens of normal-appearing adjacent mucosa, and three
      specimens of normal colonic mucosa. Colectomy specimens from five patients were
      assayed for N-myristoyltransferase activity. Subcellular distribution of N
      myristoyltransferase activity was determined. Synthetic peptides of known
      myristoylated proteins--pp60src and cyclic adenosine monophosphate-dependent
      protein kinase--were used in kinetic analyses of N-myristoyltransferase in
      colonic cancer and normal-appearing colonic tissue. All P values are two-tailed.
      RESULTS: N-Myristoyltransferase activity was increased in rat colonic tumors
      compared with normal-appearing adjacent mucosa and normal mucosa (P = .0002).
      Elevation of N-myristoyltransferase activity was present in all tumors, including
      colonic polyps. Increased N-myristoyltransferase activity was also observed in
      human colonic tumors and was predominantly cytosolic. N-Myristoyltransferase of
      colonic cancer tissues had a similar Michaelis constant but an approximate
      twofold higher maximum velocity for both the pp60src- and cyclic adenosine
      monophosphate-dependent protein kinase-derived peptides compared with N
      myristoyltransferase of normal-appearing tissue. CONCLUSIONS: This study
      demonstrates for the first time that N-myristoyltransferase activity is higher in
      colonic epithelial neoplasms than in normal-appearing colonic tissue and that an
      increase in N-myristoyltransferase activity appears at an early stage in colonic
      carcinogenesis.

PMID- 7563207
TI  - Re: Enhanced cancer growth in mice administered daily human-equivalent doses of
      some H1-antihistamines: predictive in vitro correlates.

PMID- 7563208
TI  - How does the MRP/GS-X pump export doxorubicin?

PMID- 7563209
TI  - Re: Severe interaction between methotrexate and a macrolide-like antibiotic.

PMID- 7563210
TI  - Paclitaxel in doxorubicin-resistant metastatic breast cancer patients.

PMID- 7563212
TI  - Erratum and apology re: "Detection of K-ras oncogene mutations in bronchoalveolar
      lavage fluid for lung cancer diagnosis".

PMID- 7563211
TI  - More about: a prospective study of endogenous estrogens and breast cancer in
      postmenopausal women.

PMID- 7563213
TI  - PCDDs, PCDFs, and PCBs in human milk from different parts of Norway and
      Lithuania.
AB  - Concentrations of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs)
      and dibenzofurans (PCDFs) as well as 16 polychlorinated biphenyls (PCBs) have
      been determined in pooled samples of breast milk from 10-12 mothers living in
      three different geographical areas in both Norway and Lithuania. The results
      indicate no apparent dependency of the PCDD/PCDF levels, expressed as toxic
      equivalents (TEQs), and total PCB levels on the geographical residence of the
      donors within a country. This confirms the findings from a corresponding
      Norwegian study in 1985/1986 where individual samples from the same areas were
      analyzed. Teh total TEQs, including dioxin-like PCBs, ranged from 31 to 42 pg
      TEQs/g fat in Norway and from 45 to 49 pg TEQs/g fat in Lithuania. The mean
      concentration of PCDDs/PCDFs in teh Norwegian samples (10.4 pg TEQs/g fat) was
      slightly lower than in the Lithuanian samples (14.8 pg TEQs/g fat). Dioxin-like
      PCBs were found to contribute two to three times more to the total TEQs than the
      PCDDs and PCDFs. Major contributors among the dioxin-like PCBs were PCBs 126,
      156, 114, 118, and 170. Comparison of the present data with those obtained in the
      Norwegian study in 1985/1986 shows that for PCDDs/PCDFs the mean TEQ levels have
      decreased by about 37% in the 7-yr time span, while the levels of total PCBs, as
      determined by packed-column gas chromatography, have remained unchanged or only
      slightly decreased. Future studies are necessary to confirm this potential
      temporal trend.

PMID- 7563214
TI  - Retrospective appraisal of the relationship between skin irritancy and contact
      sensitization potential.
AB  - A retrospective analysis of the association between skin irritancy and the
      potential to cause contact sensitization has been performed employing a
      historical database for 50 chemicals and formulations. Correlations between the
      results of Draize skin irritation tests and skin sensitizing activity measured
      with the occluded patch test of Buehler have been examined. Weak, but
      nevertheless statistically significant, associations between contact
      sensitization and skin irritancy have been demonstrated. It is proposed that such
      correlations are consistent with the irritant properties of a material exerting
      an important influence on the extent to which contact sensitization is induced.

PMID- 7563215
TI  - Alveolar macrophage cytokine and growth factor production in a rat model of
      crocidolite-induced pulmonary inflammation and fibrosis.
AB  - The present study was undertaken to further define the role of alveolar
      macrophages (AM) in the pulmonary response to crocidolite fibers. Briefly, groups
      of 4 male F344 rats were intratracheally instilled with saline or saline
      suspensions of crocidolite at 2 or 20 mg/kg body weight. Animals were sacrificed
      3, 7, 14, and 28 d after exposure and the lung response was characterized by
      analysis of bronchoalveolar lavage fluid (BALF) for markers of lung injury and
      inflammation. AM obtained in BALF were cultured and their production of the pro
      inflammatory cytokines, tumor necrosis factor alpha (TNF alpha), and interleukin
      1 (IL-1) were characterized along with fibronectin, a protein known to stimulate
      fibroblast migration and proliferation. Lung hydroxyproline content was
      determined 28 d after exposure and lung histopathology was characterized on d 28
      and 90 after exposure. Crocidolite instillation resulted in transient dose
      related pulmonary inflammation as evidenced by increased numbers of BALF
      neutrophils at the low dose and neutrophils, macrophages, and lymphocytes at the
      high dose. Cytotoxicity and increased permeability were demonstrated by increased
      levels of BALF lactate dehydrogenase (LDH) and total protein, respectively. AM
      TNF alpha and IL-1 production were increased only at the high crocidolite dose.
      This cytokine response was greatest at d 3 and decreased thereafter. AM TNF alpha
      and IL-1 release were positively correlated with the increased BALF neutrophils.
      In contrast to TNF alpha and IL-1, AM fibronectin release was increased at both
      the low and high doses, with the magnitude of response increasing over time.
      Consistent with previous acute asbestos inhalation studies, histopathology
      revealed inflammation localized at the level of the terminal bronchioles and
      alveolar ducts. Fibrosis was demonstrated at both doses by increased trichrome
      staining of lung tissue sections. Only the high dose resulted in a detectable
      increase in lung hydroxyproline. Given the bioactivities of TNF alpha, IL-1, and
      fibronectin, their increased production after crocidolite exposure indicates they
      contribute to the pulmonary inflammation and fibrosis occurring with this mineral
      fiber. In addition, the correlation of increased AM TNF alpha and IL-1 production
      with increased BALF neutrophils supports a role for these cytokines in
      crocidolite-induced inflammatory cell recruitment. Lastly, association of a
      persistent increase in AM fibronectin production with an eventual increase in
      lung collagen deposition extends the growing database indicating this response is
      a predictive marker of pulmonary fibrosis.

PMID- 7563216
TI  - Changes in primary and secondary lymphoid organ T-cell subpopulations resulting
      from acute in vivo exposure to propanil.
AB  - Acute exposure to the herbicide propanil is immunotoxic for selected immune
      functions, as well as causing changes in the weights of the thymus and spleen.
      Although spleen cellularity and weight increase with propanil exposure, the
      thymus: body weight ratio decreases with increasing doses of propanil. The
      present study analyzes the thymocyte subpopulations in the thymus, spleen, and
      mesenteric lymph nodes. C57Bl/6 mice were treated with either 0, 100, 150, or 200
      mg/kg propanil, and 7 d later thymocyte populations were analyzed by flow
      cytometry. In the thymus, propanil exposure resulted in a dose-dependent decrease
      in total numbers of T cells, as would be expected with its reduced weight.
      Determination of the thymocyte subpopulation distribution in the thymus showed a
      significant reduction in the number of CD3+CD4+CD8- (CD3+4+8-), CD3+CD4-CD8+
      (CD3+4-8+), and CD3+CD4+CD8+ (CD3+4+8+) cells. Percent distribution of these
      thymic cell subpopulations showed similar decreases only with the highest dose.
      Apparent dose-related decreases in the numbers of CD3-CD4+CD8+ (CD3-4+8+) cells
      were also noted and were attributed to the general decrease in total thymus
      cells. The percentage of CD3- subpopulations showed an increasing trend with
      dose, which suggests that at 7 d postpropanil exposure there may be a specific
      effect on this most immature population. Although the size and cellularity of the
      spleen were increased, no change in CD4+ or CD8+ cell distribution was observed.
      Similarly, mesenteric lymph nodes showed no changes in the cell subpopulation
      distribution between propanil-treated and control animals.

PMID- 7563217
TI  - Differences in xenobiotic detoxifying activities between bone marrow stromal
      cells from mice and rats: implications for benzene-induced hematotoxicity.
AB  - Benzene is a human carcinogen; exposure to benzene can result in aplastic anemia
      and leukemia. Data from animal models are frequently used in the risk assessment
      for benzene. In rodent studies, mice have been shown to be more sensitive to
      benzene-induced hematotoxicity than rats. In this regard, we have observed that
      bone marrow stromal cells from mice were significantly more susceptible to the
      cytotoxicity induced by the benzene metabolites hydroquinone (HQ) and
      benzoquinone (BQ) than cells from rats. Since cellular glutathione (GSH) and
      quinone reductase (QR) are known to play critical roles in modulating HQ-induced
      cytotoxicity, we have measured the GSH content and the QR and glutathione S
      transferase (GST) activity in stromal cells from both species. In rat cells, the
      GSH content and the QR specific activity were 2 and 28 times as much as those
      from mice, respectively. GSH and QR in both mouse and rat stromal cells were
      inducible by 1,2-dithiole-3-thione (D3T). D3T pretreatment of both mouse and rat
      stromal cells resulted in a marked protection against HQ-induced toxicity.
      Pretreatment of both mouse and rat stromal cells with GSH ethyl ester also
      provided a dramatic protection against HQ-induced toxicity. Conversely,
      dicoumarol, an inhibitor of QR, enhanced the HQ-induced toxicity in stromal cells
      from both mice and rats, indicating an important role for QR in modulating HQ
      induced stromal toxicity in both species. Buthionine sulfoximine (BSO), which
      depleted GSH significantly in both species, potentiated the HQ-induced toxicity
      in mouse but not in rat stromal cells. Surprisingly, incubation of stromal cells
      with BSO resulted in a significant induction of QR, especially in rats. The
      failure of BSO to potentiate HQ-induced toxicity in rat stromal cells may be due
      to the concomitant induction of QR by BSO. Overall, this study demonstrates that
      the differences in stromal cellular GSH content and QR activity between mice and
      rats contribute to their respective susceptibility to HQ-induced cytotoxicity in
      vitro, and may be involved in the greater in vivo sensitivity of mice to benzene
      induced hematotoxicity.

PMID- 7563218
TI  - Potentiation of carbon tetrachloride hepatotoxicity by inhaled methanol: time
      course of injury and recovery.
AB  - Increases in the use of methanol (MeOH) as a transportation fuel would result in
      greater potential for inhalation exposure. Because oral exposure to MeOH
      potentiates the hepatotoxicity of carbon tetrachloride (CCl4), we examined the
      ability of inhaled MeOH to potentiate CCl4 hepatotoxicity and the time course of
      injury and recovery. Adult male F-344 rats were exposed to 0 or to 10,000 ppm
      MeOH by inhalation for 6 h and gavaged with 0.075 ml CCl4/kg 24 h later.
      Hepatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30, and 61 d after CCl4
      exposure. For CCl4 alone, hepatotoxicity was most severe at 0.5 and 1 d, when
      minimal centrilobular hepatocellular necrosis and predominately mild
      centrilobular hepatocellular vacuolar degeneration occurred. By d 3, the livers
      from the CCl4 rats were histologically normal. For MeOH+CCl4, peak severity of
      hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and
      moderate/marked centrilobular degeneration occurred. MeOH+CCl4 resulted in serum
      levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      that were increased, relative to CCl4 alone, 171- and 113-fold, respectively, on
      d 1, and 166- and 140-fold, respectively, on d 1.5. Significant serum elevations
      in MeOH+CCl4 rats, relative to CCl4 alone rats, were present until d 7 and d 15
      for AST and ALT, respectively. By d 3 and d 7, degeneration and necrosis,
      respectively, due to MeOH+CCl4 were essentially resolved. On d 7, the MeOH+CCl4
      hepatic injury consisted mainly of chronic inflammation and centrilobular
      fibrosis. By d 30, the livers of MeOH+CCl4 rats were histologically normal. These
      data demonstrate that inhaled MeOH potentiates the hepatotoxicity of orally
      ingested CCl4, increasing the severity of CCl4 hepatotoxicity as well as the time
      required for recovery.

PMID- 7563219
TI  - Comparison of thermally oxidized lipids and acetaminophen with concurrent
      consumption of ethanol as inducers of liver cirrhosis.
AB  - The mechanism(s) of liver damage initiated by ingestion of toxic components of
      thermally oxidized lipids was compared in a rat model with the documented
      mechanisms of hepatic failure and necrosis initiated by acetaminophen.
      Acetaminophen (50 mg/kg body weight) or oxidized lipids (0.15 ml oxidized
      trilinolein or 1.05 ml oxidized butter oil per rat) were intubated at 12-h
      intervals to rats. Treated rats were allowed free access to food and water
      containing 3% ethanol. Changes in relative concentration of acute-phase plasma
      proteins, determined by two-dimensional (2D) immunoelectrophoresis, were taken as
      a marker of liver damage. In contrast to simple inflammation, acute-phase plasma
      proteins in this study disproportionately increased or decreased as histological
      damage of the liver due to intubation oxidized lipids or acetaminophen.
      Histological examination of liver of rats intoxicated with oxidized lipids
      revealed severe liver cirrhosis at the end of the trial, where the remaining
      viable hepatocytes were separated in a matrix of collagen. [3H1]Thymidine
      incorporation in hepatic DNA of acetaminophen or oxidized lipid intoxication
      increased in the early stages of intoxication, indicative of regenerative
      activity of the liver. Further progression of the cirrhosis inhibited continued
      liver regeneration and [3H1]thymidine incorporation into hepatic DNA. The
      cirrhotic liver at this stage failed to regenerate to the original mass upon 75%
      partial hepatectomy. Therefore, it may be concluded that hepatic necrosis
      produced by oxidized lipids or by acetaminophen may have similar mechanisms.

PMID- 7563220
TI  - Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid
      peroxidation.
AB  - Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an
      antifibrotic drug to treat the lesions of silicosis. Its mechanism in the
      treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping
      was employed to investigate the antioxidant properties of tetrandrine. The spin
      trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Tetrandine efficiently
      reacted with hydroxyl (.OH) radicals with a reaction rate of approximately 1.4 x
      10(10) M-1 s-1. The .OH radicals were generated by the Fenton reaction [Fe(II) +
      H2O2) as well as by reaction of chromium(V) with H2O2. Similar results were
      obtained using .OH radicals generated by reaction of freshly fractured quartz
      particles with aqueous medium. Tetrandrine also scavenged superoxide (O2-)
      radicals produced from xanthine/xanthine oxidase. The effect of tetrandrine on
      lipid peroxidation induced by freshly fractured quartz particles was evaluated
      using linoleic acid as a model lipid. The results showed that tetrandrine caused
      a significant inhibition on freshly fractured quartz-induced lipid peroxidation.

PMID- 7563221
TI  - Anesthetic in urine as biological index of exposure in operating-room personnel.
AB  - The aim of this study was to determine if a relationship existed between some
      inhalation anesthetics airborne exposure levels (Cl) and the concentration of
      anesthetics in samples of urine produced throughout the exposure time (Cu). The
      concentrations of nitrous oxide (N2O), halothane (fluothane), enflurane
      (ethrane), and isoflurane (forane) in the ambient atmosphere were determined in
      190 operating theaters of 41 hospitals in Italy. Nitrous oxide, halothane,
      enflurane and isoflurane were detected in the urine of 1521 exposed subjects
      (anesthetists, surgeons, and nurses). The environmental measurements were
      performed using personal passive samplers, and the biological measurements were
      performed using the head space method. Significant correlations were found
      between the anesthetics concentration in urine produced during the shift
      collected after a 4-h exposure (Cu, microgram/L) and anesthetics environmental
      concentration (Cl, ppm). The results show that the urinary anesthetic
      concentration can be used as an appropriate biological exposure index. The
      biological values (urinary concentration values) proposed are the following:
      nitrous oxide, 25 micrograms/L, for an environmental value of 50 ppm; halothane,
      97 micrograms/L, corresponding to 50 ppm of environmental exposure; 6.2
      micrograms/L, corresponding to 2 ppm of environmental exposure; enflurane, 145
      micrograms/L for an environmental exposure of 75 ppm and 5.6 micrograms/L for an
      environmental exposure of 2 ppm; isoflurane, 5.3 micrograms/L for an
      environmental exposure of 2 ppm. The values proposed are the respectively 95%
      lower confidence limit and therefore should be considered as a protection for the
      individual, especially if each biological value is corrected according to
      analytical variability of the measurements. In our opinion, the method of choice
      in the assessment of occupational exposure to inhalation anesthetics is the
      measurement of the urinary anesthetic concentration.

PMID- 7563222
TI  - Experimental strategies to promote central nervous system remyelination in
      multiple sclerosis: insights gained from the Theiler's virus model system.
AB  - The destruction of central nervous system (CNS) myelin, the lipid-rich insulator
      surrounding axons in the mammalian brain and spinal cord, is the primary
      pathological finding in multiple sclerosis. Myelin loss can result in a
      significant clinical deficit, and was originally thought to be permanent, similar
      to axonal destruction. However, myelin regeneration is now an established
      phenomenon in both human disease and animal models of CNS demyelination. In this
      review, the concept of remyelination in demyelinating diseases such as multiple
      sclerosis is discussed and the usefulness of animal models of CNS demyelination
      in developing experimental strategies to promote remyelination is examined.
      Special emphasis is given to the Theiler's murine encephalomyelitis model, which
      has been the primary animal model used to investigate therapies designed
      specifically to stimulate myelin repair.

PMID- 7563224
TI  - Functional topography of myelin-associated glycoprotein. II. Mapping of domains
      on molecular fragments.
AB  - The myelin-associated glycoprotein (MAG), an adhesion molecule of the
      immunoglobulin (Ig) superfamily with five Ig-like domains, was investigated with
      regard to its binding site(s) for the neuronal cell surface, collagen I, and
      heparin, using a panel of new monoclonal antibodies and cyanogen bromide cleavage
      fragments of MAG. All antibodies generated competed with each other for binding
      to MAG, indicating that they reacted with identical or closely related epitopes.
      Mapping of the reactive epitopes on recombinant deletion fragments of MAG
      expressed by Chinese hamster ovary (CHO) fibroblasts showed reactivity of
      monoclonal antibody 513 with domains I, II, and III, comprising the amino
      terminal end of the extracellular domain. Monoclonal antibody 15 recognized
      domain III only. Binding of MAG-containing liposomes to neurons was blocked by
      antibodies 15 and 513. Cyanogen bromide (CNBr) fragments of domains I, II, and
      III bound to collagen type I under isotonic buffer conditions. CNBr fragments
      containing domains I and II were involved in binding to heparin. These
      observations suggest that domain III may be important for binding to the neuronal
      cell surface receptor for MAG, while domains I, II, and III interact with
      collagen type I and domains II and III with heparin.

PMID- 7563225
TI  - Glia-to-axon communication: enrichment of glial proteins transferred to the squid
      giant axon.
AB  - The transfer of newly synthesized proteins from the glial sheath into the axon is
      a well-documented process for the squid giant axon. In this study, we used a
      novel approach to separate the transferred glial proteins (TGPs) from the
      endogenous axoplasmic proteins of the squid giant axon. Axoplasm, containing
      radiolabelled TGPs, was extruded as a cylinder and immersed in an intracellular
      buffer. After 1-30 min, the TGPs were enriched in the intracellular buffer,
      because they were eluted from the axoplasm into the intracellular buffer much
      faster than the endogenous axoplasmic proteins. Most of the TGPs enriched in the
      intracellular buffer did not pellet when centrifuged at 24,000 g for 20 min and
      were susceptible to protease digestion without the addition of Triton X-100.
      Additionally, transmission electron microscopic autoradiography of intact axons,
      containing radiolabelled TGPs, suggested that most TGPs were not associated with
      vesicular organelles within the axon. We conclude that most of the TGPs are not
      contained within vesicles in the axoplasm of the squid giant axon, as would be
      expected if the mechanism of glia-to-axon transfer were conventional exocytosis
      endocytosis or microphagocytosis.

PMID- 7563223
TI  - Expression of receptor protein tyrosine phosphatase-sigma (RPTP-sigma) in the
      nervous system of the developing and adult rat.
AB  - The expression of receptor protein tyrosine phosphatase-sigma (RPTP-sigma) mRNA
      during rat development was examined by Northern blot and in situ hybridization
      analyses. Northern blot analysis revealed that the two transcripts (5.7 kb and
      6.9 kb) had different spatial and temporal patterns of expression. The 6.9-kb
      transcript was more abundant during embryonic development, whereas the 5.7-kb
      transcript was more abundant during postnatal development and in the adult. In
      situ hybridization revealed that RPTP-sigma mRNA was widely expressed throughout
      the central and peripheral nervous system during embryonic development. Very high
      levels were seen in the ventricular zone, subventricular zone, cortex, dorsal
      root ganglia, cranial nerve ganglia, olfactory epithelium, and retina. During
      postnatal development the level of expression decreased in most brain regions.
      However, high levels continued to be seen in the hippocampus. Emulsion
      autoradiography revealed that the majority of RPTP-sigma mRNA is expressed in
      neurons. Northern analysis showed that cultured glial cells expressed the 6.9-kb
      transcript, but not the 5.7-kb. RPTP-sigma mRNA expression profiles were clearly
      distinct from those of leukocyte antigen-related protein (LAR), a closely related
      RPTP. The spatiotemporal pattern of RPTP-sigma mRNA expression indicates that
      RPTP-sigma may play a role in the development of the nervous system.

PMID- 7563227
TI  - Inhibition of neurite outgrowth following intracellular delivery of anti-GAP-43
      antibodies depends upon culture conditions and method of neurite induction.
AB  - NB2/dl neuroblastoma cells acquire a neuronal phenotype in response to several
      differentiating agents, including dibutyryl cAMP (dbcAMP) and the withdrawal of
      serum. As shown previously, antibodies to the growth-associated protein, GAP-43,
      introduced intracellularly using a lipid carrier, blocked the differentiation
      induced by dbcAMP. Antibodies to GAP-43, at a low concentration, also blocked
      neurite outgrowth induced by serum withdrawal when cells were grown on a
      relatively unadhesive substrate. On more adhesive substrates such as poly-L
      lysine and laminin, however, anti-GAP-43 antibodies had less of an effect on
      neurite outgrowth. Previous studies have shown that the increased adhesivity of
      laminin allows a small but significant population of neurites to grow from serum
      deprived cells, even in the presence of the microtubule-depolymerizing drug,
      colchicine. The outgrowth of this population of neurites was blocked by
      antibodies to GAP-43. These results are in conformity with recent studies showing
      that the requirement for GAP-43 in neuritogenesis may be related to membrane
      adhesiveness, and may contribute to an understanding of some of the apparent
      discrepancies in the literature concerning the involvement of GAP-43 in neuronal
      differentiation.

PMID- 7563228
TI  - Axonal atrophy in aging is associated with a decline in neurofilament gene
      expression.
AB  - Neurofilaments (Nfs) are major determinants of axonal caliber. Nf transcript
      levels increase during development and maturation, and are associated with an
      increase in Nf protein, Nf numbers, and caliber of axons. With aging there is
      axonal atrophy. In this study we asked whether the axonal atrophy of aging was
      associated with a decline in Nf transcript expression, Nf protein levels, and Nf
      numbers. Expression of transcripts for the three Nf subunits was evaluated in
      dorsal root ganglia (DRG) of Fischer-344 rats aged 3-32 months by Northern and in
      situ hybridization. There was an approximately 50% decrease in Nf subunit mRNA
      levels in DRG of aged (> 23 months) as compared to young and mature (3 and 12
      months) rats, whereas expression of another neuronal mRNA, GAP-43, showed no
      decline. Western analysis showed a corresponding decrease in Nf subunit proteins
      and no decline in GAP-43. Morphometric analysis showed a 50% decrease in Nf
      numbers within axons. The decrease in Nf gene expression and Nf numbers was
      accompanied by a decrease in cross-sectional area and circularity of all
      myelinated fibers, with the largest fibers showing the most marked changes, and a
      shrinkage in the perikaryal area of large neurons. Furthermore, we found a
      concomitant decrease in the expression of transcripts for the nerve growth factor
      receptors trkA and p75 with aging. Although the mechanisms leading to the
      decrease in Nf gene expression with aging are not known, a decrease in the
      availability of growth factors, or the neuron's ability to respond to them, may
      play a role in this process.

PMID- 7563226
TI  - 192IgG-saporin immunotoxin-induced loss of cholinergic cells differentially
      activates microglia in rat basal forebrain nuclei.
AB  - To characterize the specificity of a novel cholinergic immunotoxin (conjugate of
      the monoclonal antibody 192IgG against the low-affinity nerve growth factor
      receptor with the cytotoxic protein saporin), coronal sections through the basal
      forebrain of adult rats, that received a single intracerebro-ventricular
      injection of 4 micrograms of 192IgG-saporin conjugate, were subjected to
      histochemical and immunocytochemical procedures to evaluate cholinergic (choline
      acetyltransferase (ChAT)-immunoreactive, acetylcholinesterase-positive, NADPH
      diaphorase-positive) and GABAergic structures (parvalbumin-immunoreactive,
      labeling of perineuronal nets with Wisteria floribunda agglutinin) as well as
      microglia (visualized with Griffonia simplicifolia agglutinin) and astrocytes
      (immunostaining for glial fibrillary acidic protein). Seven days following
      injection of the immunotoxin, ChAT-immunoreactive cells nearly completely
      disappeared throughout the magnocellular basal forebrain complex, including
      globus pallidus, as compared to vehicle-injected controls. However, there was no
      significant difference in the number of ChAT-positive cells in the adjacent
      ventral pallidum and in the caudate-putamen of immunolesioned and control
      animals. NADPH-diaphorase-containing cells, including a significant subpopulation
      of cholinergic cells, also strikingly decreased in number by more than 90% in the
      magnocellular basal forebrain complex following immunolesion, and only a few
      noncholinergic diaphorase-positive cells survived in the medial septum, vertical
      and horizontal diagonal band, and nucleus basalis of Meynert. In contrast, the
      number of parvalbumin-containing GABAergic projection neurons in the septum
      diagonal band of Broca complex and nucleus basalis of Meynert from immunolesioned
      rats was not different from that of vehicle-injected control animals.
      Immunolesioning also did not result in any change in either number or shape of
      cells surrounded by perineuronal nets, which are frequently associated with
      parvalbumin-containing GABAergic neurons. Seven days following injection of the
      immunotoxin, a very strong activation of microglia with an identical distribution
      pattern was observed in all experimental animals. Large numbers of activated
      microglia were found in all magnocellular basal forebrain nuclei, corresponding
      to the distribution of degenerating cholinergic cells. Additionally,
      immunolesioning also resulted in a dramatic activation of microglia in the
      lateral septal nuclei, which are known to be almost free of cholinergic cells,
      but not of penetrating cholinergic dendrites in adjacent zones, and in the
      ventral pallidum, where there was no observed loss of cholinergic cells. There
      was no significant increase in microglia activation in striatum and cortical
      areas, and no astrocytic response in any of the basal forebrain nuclei at this
      particular time point of survival. These results suggest that 192IgG-saporin
      specifically destroys basal forebrain cholinergic neurons and does not suppress
      their neuronal activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7563230
TI  - Adaptation of C6 glioma cells to serum-free conditions leads to the expression of
      a mixed astrocyte-oligodendrocyte phenotype and increased production of neurite
      promoting activity.
AB  - C6 cells were adapted to proliferate in defined culture medium to allow the study
      of long-term effects of serum-free growth conditions on their phenotypic antigen
      expression and production of neurite promoting factors (NPFs). Cultures were
      grown in either Ham's F-12 or supplemented Opti-MEM-I containing 15% heat
      inactivated horse serum and 2.5% fetal calf serum (serum-containing) or in
      supplemented Opti-MEM-I alone (serum-free). Immunocytochemical and
      immunofluorescence techniques were used to determine the antigenic expression of
      A2B5, galactocerebroside (GalC), and glial fibrillary acidic protein (GFAP) in
      passage matched and sister cultures of serum and serum-free grown C6 cells. When
      C6 cells were grown under serum-containing conditions, two populations of cells
      were seen: young oligodendrocytes (A2B5+, GFAP-, GalC+), and mixed astrocyte
      oligodendrocyte phenotype (A2B5+, GFAP+, GalC+). After adaptation of the C6 cells
      to serum-free conditions over 2-3 passages, only one population of cells was
      observed, the mixed astrocyte-oligodendrocyte phenotype. The serum-free
      conditions also resulted in greater staining of the C6 cells. Conditioned media
      from the two growth conditions were fractionated by ultrafiltration into two
      fractions: components > 50 kDa and components of 10-50 kDa. The amount of neurite
      promoting activity seen between the two culture conditions resulted in a 3-fold
      increase in NPF activity under serum-free conditions in the > 50 kDa fraction.
      The 10-50 kDa fraction only expressed NPF activity if obtained from the serum
      grown C6 cells. This alteration in NPF activity appears to be the result of the
      phenotypical alteration of the C6 cells, and may suggest that the NPF activities
      from the two culture conditions may not be identical.

PMID- 7563229
TI  - NGF-producing transfected 3T3 cells: behavioral and histological assessment of
      transplants in nigral lesioned rats.
AB  - The rodent fibroblast clonal cell line, 3T3, was retrovirally transfected with
      the rat nerve growth factor (NGF) gene and selected for NGF synthesis. This study
      tested the hypothesis that transplanted 3T3 cells, transfected to secrete nerve
      growth factor (3T3NGF+), change motor behavioral indices created by striatal
      denervation in a dose-dependent fashion. 3T3NGF+ cells were transplanted into the
      lateral ventricle of rats following ipsilateral lesions of the substantia nigra
      pars compacta by stereotaxic injections of 6-hydroxydopamine (10 micrograms), an
      established lesion model. Control groups included vehicle injections and
      transplanted untransfected cells. The extent of the lesions was measured by
      determining rotational behavior before and two weeks after transplantation.
      Immediately prior to transplantation, cells were incubated with the fluorescent
      dye marker, Dil. To assess cell viability, whole brains were cryosectioned and
      examined for Dil-labeled 3T3 cells using fluorescent microscopy. The number of
      Dil-labeled profiles in five animals per group were counted in at least five
      noncontiguous sections per animal. From these data a statistically derived
      estimate of viable, transplanted 3T3 cells was obtained. The number of surviving
      transplanted cells correlated with the behavioral changes measured. The 3T3NGF+
      transplants reduced rotational behavior, while control 3T3 transplants
      exacerbated rotational behavior. Thus, while NGF delivery was found to be
      beneficial, it was apparent that naive 3T3 had detrimental effects. These results
      underscore the importance of making dose-response measurements when attempting
      transplant-based modifications of CNS behavior.

PMID- 7563231
TI  - Characterization of gonadotropin-releasing hormone (GnRH)-immunoreactive protein
      in the rat pineal gland.
AB  - The aim of the present study was to characterize GnRH-like substance(s) in the
      rat pineal gland using a monoclonal antibody, LRH13, as a probe. The epitope of
      LRH13 is between 2nd and 5th amino acid residues of the mammalian GnRH, and its
      immunological characters were previously defined by us. LRH13 could show strong
      immunological signal on the rat pineal gland. Immunoblot after SDS-PAGE of the
      pineal gland preparations showed a LRH13 immunoreactive band with apparent mol wt
      52 kilo-Dalton (kD), which is much bigger than that of hypothalamic GnRH
      precursor (10 kD). The 52 kD protein, however, was detected from insoluble
      fraction of the pineal homogenate and liberated from the fraction by Triton X-100
      (2%) treatment. On the other hand, NaCl (140 mM and 500 mM) or EDTA (10 mM)
      treatment failed to liberate. Two-dimensional gel electrophoresis showed that the
      52 kD protein is a mixture of two proteins with different isoelectric points (pI
      approximately 6.8 and 7.0). Both proteins showed identical patterns of peptide
      mapping by V8 protease digestion, and they might be originated from the same
      peptide. These results suggest that the rat pineal GnRH-immunoreactive substance
      has a unique property as a membrane associate protein.

PMID- 7563232
TI  - Bilateral gliosis in unilaterally lesioned septohippocampal system: changes in
      GFAP immunoreactivity and content.
AB  - Unilateral damage to the lateral fimbria led to a bilateral gliosis in the septum
      and hippocampus. The gliosis was manifested by an increase in GFAP staining,
      accompanied by an increased number of glial fibrillary acidic protein (GFAP)(+)
      cells and GFAP content; the latter however was not visible in the contralateral
      septum. In general, the contralateral reaction appeared weaker than the
      ipsilateral one. The pattern of contralateral increase in GFAP-immunoreactivity
      (IR) matched almost exactly that observed on the ipsilateral side in the
      hippocampus (the most evident increase was seen in the oriens and pyramidal
      layers of cornu Ammonis 3 and in polymorphic area of gyrus dentatus). In the
      septum the bilateral increase in GFAP-IR was mainly visible in the dorsolateral
      quadrant of the structure; however in the ipsilateral side it spread over the
      whole half of the structure. The astrocytic responses in the septum and
      hippocampus were not equivalent: they differed mainly with regard to the increase
      of GFAP(+) cells (over 300% of control in the anterior part of the septum and
      only about 120% in the dorsal hippocampus). The differences between the
      percentage increases of other gliotic indices: GFAP-IR and GFAP content. Various
      possibilities that may account for the occurrence of contralateral gliosis are
      discussed, the most plausible being the contribution of interhemispheric and
      intraseptal links and the action of some diffusible agents. We suggest that
      bilateral gliosis may have an impact on compensatory postlesion processes,
      possibly by providing trophic support to impaired neurons.

PMID- 7563233
TI  - Stimulation of choline acetyl transferase activity by l- and d-carnitine in brain
      areas of neonate rats.
AB  - Acetyl-CoA supply to the cytosol and its regulatory influence on acetylcholine
      biosynthesis is still an unsolved question. Acetylcarnitine through the carnitine
      acetyl transferase (CarAT) system has been proposed to be the acetyl donor in
      this process. Carnitine isomers were injected into rat developing brains every
      day for 14 days after birth. Results showed that carnitine and its associated
      forms produced a choline acetyl transferase (ChAT) activity increase in the
      striatum and the hippocampus. Carnitine acetyl transferase activity was
      stimulated by the treatment of l-carnitine in the hippocampus but it remained
      unchanged in the striatum and the cerebral cortex. These results suggest that
      ChAT and CarAT activities might be modulated by Acetyl-CoA derived preferentially
      from acetylcarnitine. It is suggested that ChAT activity enhancement depends on
      intrinsic and extrinsic cholinergic afferents to these brain areas.

PMID- 7563234
TI  - Thyroid hormone and conditioned medium effects on astroglial cells from
      hypothyroid and normal rat brain: factor secretion, cell differentiation, and
      proliferation.
AB  - The effects of triiodothyronine (T3) on cell morphology were examined in cerebral
      hemisphere and cerebellar astrocyte cultures obtained from normal and hypothyroid
      neonatal rats. T3-treatment induced morphological changes in astrocytes from
      cerebral hemispheres. This morphological effect was produced earlier if
      astrocytes were treated with conditioned medium obtained from cerebral hemisphere
      astrocyte cultures previously exposed to 50 nM T3. T3 or conditioned medium
      treatment produced faster morphological changes in hypothyroid rat cerebral
      hemisphere astrocyte monolayers. Cerebellar astrocytes from normal brain did not
      respond to thyroid hormone with morphological changes, but proliferated after T3
      treatment. However, hypothyroid cerebellar astrocyte cultures exhibited
      morphological changes, differently than normal cells. We verified that T3 may
      induce astrocyte secretion of factor(s) that promotes morphological
      differentiation in cerebral hemisphere astroglial cultures and stimulates the
      proliferation of cerebellar astrocytes. Astrocytes obtained from hypothyroid
      animals were more sensitive to secreted factors than normal cells. These results
      emphasize the heterogeneity and the importance of glial cells to normal brain
      development and open new questions about thyroid hormone therapy in
      hypothyroidism.

PMID- 7563235
TI  - Glutamate-induced antigenic changes of phospholipase C-delta in cultured cortical
      neurons.
AB  - Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal
      transduction. It was previously demonstrated that an antibody to an isozyme of
      PLC, PLC-delta, produces intense staining of neurofibrillary tangles (NFT), the
      neurites surrounding senile plaque (SP) cores and neuropil threads in the brains
      of patients with Alzheimer's disease (AD). Although the etiology of neuronal
      degeneration in AD is still to be defined, excitotoxic glutamate might be a
      candidate. In the present study, an anti-PLC-delta antibody was used to examine
      the influence of glutamate on PLC-delta immunoreactivity in cultured rat cortical
      neurons. Exposure to glutamate caused the death of cultured cortical neurons and
      exhibited increased immunostaining with the anti-PLC-delta antibody. Subtoxic
      doses of glutamate also increased PLC-delta immunoreactivity in a dose-dependent
      manner. Both glutamate-induced neuronal degeneration and the increases in PLC
      delta immunoreactivity were prevented by removal of extracellular Ca2+ or the
      application of an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. The
      glutamate-induced increase in PLC-delta immunoreactivity was also prevented by N
      omega-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor. These results
      suggest that NO formation secondary to Ca2+ influx by NMDA receptor activation
      leads to similar modifications of PLC-delta to those seen in AD.

PMID- 7563236
TI  - Deciphering the native GABAA receptor: is there hope?
AB  - The bewildering number of GABAA receptor subunits, their regionally dependent
      expression in the brain, and their supernumerary expression in single cells
      present major challenges in studying the function of native GABAA receptors.
      Which subunit combinations actually exist in native neurons? In this mini-review,
      GABAA receptor subunit diversity is considered in light of using the wealth of
      "structure-function" information gained from studying recombinant receptor to
      predict the subunit composition and functional properties of native GABAA
      receptors.

PMID- 7563237
TI  - Demonstration of interleukin-3 receptor-associated antigen in the central nervous
      system.
AB  - We previously reported that interleukin-3 (IL-3) acts as a neurotrophic factor
      for cholinergic neurons. However, it has not yet been determined whether the
      action is derived from the interaction of IL-3 with IL-3 receptors. As the first
      step to study IL-3 receptors in the central nervous system, we examined the
      presence and localization of IL-3 receptor-associated antigen (IL-3RAA) in mouse
      and rat brain. Immunohistochemically, IL-3RAA, which is closely involved both in
      the IL-3 binding to IL-3 receptors and the tyrosine phosphorylation in the signal
      transduction for IL-3 in hematopoietic cells, was demonstrated in neurons
      throughout the brain. This was confirmed in primary cultured neurons and neuronal
      cell lines by immunocytochemistry and flow cytometry. The staining intensity
      varied among regions and the most intense immunoreactivity for IL-3RAA was found
      in large neurons in the magnocellular basal nuclei, pyramidal cells in the
      cerebral cortex, and neuronal cells in some nuclei of the brainstem. Not only
      cholinergic cell lines derived from the septal region but also other neuronal
      cell lines exhibited IL-3RAA immunoreactivity by flow cytometry. Therefore, we
      conclude that IL-3RAA is present in a wide variety of neurons in the brain
      including cholinergic neurons of the basal forebrain. Western blot analysis
      revealed that the candidates for IL-3RAA are 145, 100, and 50 kDa proteins both
      in neuronal and IL-3-dependent cell lines.

PMID- 7563238
TI  - Differential expression of exons 10 and 11 in normal tau and tau associated with
      paired helical filaments.
AB  - Antibodies were raised to two synthetic peptides with amino acid sequences
      encoded by a variable region of exons 10 and 11 of the tau gene. The affinity
      purified antibodies, designated E-10 and E-11, were used to determine whether PHF
      tau and normal tau differ in variants containing three or four repeats in the
      microtubule-binding domain, respectively. Normal adult human brain was shown by
      gel electrophoresis to contain six isoforms of tau. All of the isoforms reacted
      with E-11, whereas only four of them with slower electrophoretic mobility were
      recognized by E-10. Fetal brain tau was readily recognized by E-11 but reacted
      poorly with E-10. In PHF preparations, E-11 bound to all three polypeptides of
      PHF-tau of 68 kD, 64 kD, and 60 kD and reacted intensely with a material smearing
      from the top of the gel to about the 50-kD region. In contrast, E-10 only weakly
      recognized the two higher molecular weight PHF-tau polypeptides of 68 kD and 64
      kD, as well as smeared material, and the binding was not affected by phosphatase
      treatment. Using recombinant tau with four repeats as a reference, the
      immunoreactivity of E-10 with PHF-tau was estimated to be approximately 5% of
      that of E-11. By comparison, the immunoreactivity of E-10 with four isoforms of
      normal tau was comparable to that of E-11. These results indicate that the ratio
      of three vs. four repeat variants in PHF-tau is higher than in normal tau and
      suggest that Alzheimer disease may be associated with the disproportional
      expression of fetal (or juvenile) forms of tau. Alternatively, the weak
      reactivity of PHF-tau with E-10 antibody could be due to post-translational
      modifications other than phosphorylation.

PMID- 7563239
TI  - Chemotaxis and accumulation of nerve growth factor by microglia and macrophages.
AB  - Astrocytes and microglia play a critical role in the reaction of the central
      nervous system (CNS) to trauma. Although both astrocytes and microglia can
      produce it, accumulation of immunoreactive nerve growth factor (the prototype
      neurotrophin important for the survival of several classes of neurons) was
      observed selectively in cultured microglia and macrophages, rather than in
      astrocytes. Furthermore, microglia were found to display chemotaxis toward a
      localized source of nerve growth factor and, as demonstrated by autoradiography,
      take up extracellular nerve growth factor. These findings suggest that microglia,
      the brain's own macrophages, participate in the regulation of nerve growth factor
      availability in a site-specific manner. This novel function may assume a general
      importance both in the CNS and the peripheral nervous system at critical times
      after trauma when this neurotrophin is needed for nerve cell survival.

PMID- 7563240
TI  - Localization of constitutive and hyperthermia-inducible heat shock mRNAs (hsc70
      and hsp70) in the rabbit cerebellum and brainstem by non-radioactive in situ
      hybridization.
AB  - Neural expression of constitutive hsc70 mRNA and hyperthermia-inducible hsp70
      mRNA is examined using radioactive and non-radioactive in situ hybridization
      procedures. A strong induction of hsp70 mRNA was noted in cell populations in
      cerebellar layers and in the brainstem which demonstrated expression of mRNA
      encoding proteolipid protein, an oligodendrocyte marker. The non-radioactive in
      situ hybridization procedure using digoxigenin (DIG)-UTP-labeled riboprobes
      permitted improved signal localization, and stress-inducible hsp70 mRNA was
      detected at the cytoplasmic cap areas of individual oligodendrocytes. Cell types
      which express constitutive members of the hsc/hsp70 multigene family were also
      identified. Neurons in the brainstem and in the deep white matter and molecular
      layer of the cerebellum showed expression of hsc70 mRNA while signal was not
      detected in adjacent glial cells. A neuron-specific enolase riboprobe aided in
      the identification of neuronal cell types. The non-radioactive DIG riboprobe
      revealed that hsc70 mRNA was highly localized to the cytoplasm of individual
      neurons. High constitutive levels of hsc70 in certain neurons may dampen hsp70
      induction after hyperthermia in these cell populations.

PMID- 7563241
TI  - Increase in GAP-43 and GFAP immunoreactivity in the rat hippocampus subsequent to
      perforant path kindling.
AB  - Kindling is an animal model of epilepsy which is accompanied by morphological and
      biochemical changes in the brain, including sprouting of fibers and increased
      transmitter release. Here we have examined the immunocytochemical expression of
      1) GAP-43, a growth-associated protein, which is a neuron-specific PKC substrate,
      particularly expressed in development and regeneration and 2) glial fibrillary
      acidic protein (GFAP), part of the astrocytic cytoskeleton, after perforant path
      kindling. Subsequent to kindling, GAP-43 immunoreactivity was increased in CA1
      stratum lacunosum-moleculare and the inner and outer molecular layer of the
      fascia dentata. Other hippocampal subregions showed a lower increase. GFAP
      immunoreactivity was increased in the entire hippocampus, but especially in
      stratum lacunosum-moleculare of the CA1 and the hilus of fascia dentata. The
      difference between the number of GFAP-positive profiles in the hippocampus of
      control rats and in fully kindled rats was found to be non-significant. We
      interpret these findings as being related to both plastic neuronal changes and
      possible neuronal degeneration.

PMID- 7563242
TI  - Studies on T-cell receptors involved in experimental autoimmune encephalomyelitis
      using the complementary peptide recognition approach.
AB  - Based upon Blalock's complementary recognition approach, a complementary or
      antisense peptide (CP) was designed to the experimental autoimmune
      encephalomyelitis (EAE) epitope peptide, rat myelin basic protein (MBP) peptide
      72-82. This peptide (EAE CP) was shown to have some sequence similarities to T
      cell receptors (TCR) and MHC II molecules in a sequence homology search. Solid
      phase binding assays demonstrated specific and high affinity binding (3 and 4
      microM) between the EAE CP and the rat and guinea pig EAE epitope peptides (Rt72
      82 and Gp69-82), respectively. This EAE CP was also found to be immunogenic in
      rats in an ear swelling test for delayed type hypersensitivity (DTH) reactions
      and an ELISA for antibody responses. However, a rabbit antibody generated to EAE
      CP was shown to be unable to stain the V beta 8+ EAE susceptible T-cells in
      immunofluorescence analyses. This EAE CP was also used in attempts to down
      regulate EAE and the results showed that prior immunization with EAE CP in
      complete Freund's adjuvant could not prevent the Lewis rats from developing EAE.
      Although the data on sense-antisense peptide interaction were positive and the
      EAE CP was immunogenic, the inability of EAE CP to regulate EAE indicates that
      the CP approach may not be generally applicable.

PMID- 7563243
TI  - Specificity of nerve growth factor signaling: differential patterns of early
      tyrosine phosphorylation events induced by NGF, EGF, and bFGF.
AB  - The specificity of nerve growth factor (NGF) action was examined by comparing
      early tyrosine phosphorylation events induced by NGF, epidermal growth factor
      (EGF), and basic fibroblast growth factor (bFGF). In PC12 cells, administration
      of either the differentiation factor NGF or the mitogenic factor EGF led to
      tyrosine phosphorylation of multiple polypeptides in the 100-110 kDa size range
      associated with PI-3 kinase. However, NGF induced a more prolonged
      phosphorylation, relative to a transient EGF effect. In contrast, the
      differentiation factor bFGF failed to induce measurable tyrosine phosphorylation
      of PI-3 kinase-associated proteins. Similarly, NGF but not bFGF induced marked
      tyrosine phosphorylation of PLC gamma, another early signaling molecule,
      suggesting that multiple pathways exist for promoting differentiation, and/or
      that these signaling molecules are not essential for differentiation. TrkA
      signaling was also compared between PC12 cells and NIH-3T3 cells heterologously
      expressing trkA, where receptor activation promotes mitogenesis. In this
      comparison, significant differences were observed in the tyrosine phosphorylation
      pattern of PI-3 kinase-associated polypeptides, suggesting the existence of cell
      type-specific molecular interactions influencing trkA signaling. Mechanistically,
      NGF stimulation of PC12 cells resulted in a weak or possibly indirect association
      between trkA and PI-3 kinase. Furthermore, NGF did not appear to activate or
      substantially alter the overall level of PI-3 kinase activity, raising the
      possibility that ligand-induced phosphorylation may serve instead to relocalize
      constitutively active PI-3 kinase molecules within the cell. Taken together, data
      presented suggest that the temporal pattern of induced phosphorylation, the
      nature of induced associations with other phosphoproteins, and cell type-specific
      components may all contribute to the generation of NGF signaling specificity.

PMID- 7563244
TI  - Selective in vitro blockade of neuroepithelial cells proliferation by
      methylazoxymethanol, a molecule capable of inducing long lasting functional
      impairments.
AB  - In order to characterize the antiproliferative effect of methylazoxymethanol
      neuroepithelial cells derived from the rat striata primordia at embryonic day 14
      have been exposed to graded doses of this compound. It was found that
      methylazoxymethanol application to striatal neuroblasts elicits a blockade of
      cell proliferation at a dose which does not interfere with cell survival. By
      using synchronized cells and short term exposures to this compound, we found that
      the antiproliferative effect of methylazoxymethanol is strikingly correlated to
      the number of cells actively dividing in culture, thus indicating that the cells
      targeted by methylazoxymethanol must be in an active mitotic phase. To test for
      the selectivity of action of Methylazoxymethanol for dividing neuroblasts either
      cultures composed of mature proliferating astrocytes or muscle cells have been
      subjected to the same treatment. It has been observed that astrocytes
      proliferation was not affected by the dose of methylazoxymethanol shown to be
      effective on neuroepithelial cells. Finally we demonstrated that
      methylazoxymethanol is able only transiently to interfere with smooth muscle cell
      division, further supporting its selectivity of action within the developing CNS.

PMID- 7563245
TI  - Mitogen induced proliferation of isolated adult mouse Schwann cells.
AB  - The proliferation of neonatal Schwann cells (SCs) in response to mitogenic agents
      has been well analyzed in vitro, but a limited range of mitogens have been
      defined. We investigated whether three identified neonatal SC mitogens [glial
      growth factor (GGF), platelet-derived growth factor BB (PDGF-BB), and basic
      fibroblast growth factor (bFGF)] are required to stimulate mitosis of adult SCs.
      Adult SCs were isolated from mouse sciatic nerves by mechanical and chemical
      dissociation, following three experimental steps: 1) culturing the dissociated
      cells for 24 hr in 10% FCS-F12 medium, 2) culturing these cells in serum-free
      medium for the next 48 hr, and 3) purifying adult SCs by differential adhesion.
      We describe a new method for preparation of SCs from peripheral nerves of adult
      mouse that provides 99.5% pure SCs populations at cell yields of greater than 3 x
      10(3) cells/mg of starting nerve wet weight within 5 culture days. Although
      mitosis of SCs in culture in response to mitogens requires the presence of serum,
      the complex nature of serum renders difficult a complete analysis of mitogens
      required for SCs DNA synthesis, so we examined the proliferating response of
      adult SCs to GGF, PDGF-BB, and bFGF in serum-free medium. GGF alone had
      mitogenicity for adult SCs in a dose-dependent manner, and synergistic activation
      coupling with forskolin was not observed. Neither PDGF-BB nor bFGF was mitogenic
      for adult SCs when used alone or with forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563246
TI  - Acetyl- and butyrylcholinesterase activities in the rat retina and retinal
      pigment epithelium.
AB  - The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in
      the neural retina and retinal pigment epithelium (RPE) of adult rats were
      determined. The tissues were extracted with a saline buffer to release the
      soluble enzymes (S1) and the pellet re-extracted with Triton X-100 to detach the
      membrane-bound enzymes (S2). Less than 5% of the cholinesterase activity measured
      in retina and almost 30% of that assayed in RPE was due to BChE. About 20% and
      10% of the AChE in retina and RPE was brought into solution with a saline buffer
      and the rest with a detergent-containing buffer. Main AChE molecular forms of
      10.5S (hydrophilic G4H), 9.5S (amphiphilic G4A) and 3.0S (amphiphilic G1A) were
      identified in retina by subjecting the supernatant S1 to sedimentation analysis
      in sucrose gradients made with Brij 96. Amphiphilic G4 and G1 AChE were found in
      S2. Analysis of the soluble fractions obtained from RPE in the gradients made
      with Brij 96 revealed 16.0S (asymmetric A12), 10.5-10.0S (globular G4H + G4A),
      4.5S (G2A), and 3.0S (G1A) AChE forms in S1, whereas G4A, G2A, and G1A enzyme
      molecules predominated in S2. Our results show that amphiphilic tetramers and
      monomers of AChE are abundant in neural retina, and enzyme tetramers, dimers, and
      monomers in RPE. The AChE in the neural retina might be involved in cholinergic
      actions. The enzyme function in the retinal pigment epithelium remains to be
      established.

PMID- 7563247
TI  - Neurons express ciliary neurotrophic factor mRNA in the early postnatal and adult
      rat brain.
AB  - The regional and subcellular localization in the central nervous system (CNS) of
      postnatal day 5, day 15, and adult rats of ciliary neurotrophic factor (CNTF)
      mRNA was examined by in situ hybridization with biotinylated riboprobes. Probe
      specificity was determined by Northern blot analysis of poly(A)+ RNA extracted
      from adult rat brain using digoxigenin labeled riboprobes and chemiluminescent
      detection. Both a 4 kb and a 1.2 kb transcript were detected in the cortex and
      brainstem. In situ hybridization revealed that CNTF mRNA was widely distributed
      in neurons and glia throughout the CNS at each of the developmental time points.
      The density of the neuronal hybridization signal was found to be greater in
      neuronal nuclei than in their cytoplasm. In the nucleus of most neurons, CNTF
      mRNA distribution was concentrated in a perinucleolar fashion. Alternate sections
      from the same animals, which were incubated with a specific polyclonal antibody
      against a CNTF peptide fragment, revealed that both neurons and glia in postnatal
      day 5, day 15, and adult rat brain were immunoreactive for CNTF.

PMID- 7563248
TI  - Noradrenaline-induced stimulation of glutamine metabolism in primary cultures of
      astrocytes.
AB  - Effects of noradrenaline and of adrenergic subtype specific agonists on the
      uptake and metabolism of [14C]glutamine and [14C]glutamate in primary cultures of
      mouse astrocytes have been investigated. The total uptake of radioactivity from
      extracellular [14C]glutamine into the cells was enhanced during exposure to 100
      microM noradrenaline, isoproterenol, or clonidine. This is partly due to an
      increased radioactivity in the glutamine pool and partly due to an increased
      formation of labeled glutamate from glutamine, which had become very marked (66%)
      after 240 min of incubation. The CO2 formation from labeled glutamine during 4 hr
      of incubation was enhanced about twofold in the presence of noradrenaline. Ten
      millimolar amino oxyacetic acid (AOAA), a transamination inhibitor, had no effect
      on CO2 formation from glutamine, indicating that the formation of alpha
      ketoglutarate from glutamate occurs as an oxidative deamination. The stimulation
      of 14CO2 production from labeled glutamine was at least as large when glucose was
      deleted from medium, suggesting that the increased 14CO2 formation represents a
      stimulation of glutamine metabolism as such and is not only a reflection of an
      increase in oxidative metabolism of glucose and a bidirectional exchange between
      alpha-ketoglutarate and glutamate. The opposite process, incorporation of
      radioactivity from labeled glutamate into glutamine, was not enhanced in the
      presence of noradrenaline. The findings suggest that noradrenaline stimulates the
      rates of glutamine uptake, glutamate synthesis, and CO2 production from glutamine
      and thus increases energy supply to astrocytes but has no effect on the opposite
      reaction, i.e., glutamine formation from glutamate, a reaction of importance for
      neuronal-astrocyte interations.

PMID- 7563249
TI  - Expressions of nerve growth factor and p75 low affinity receptor after transient
      forebrain ischemia in gerbil hippocampal CA1 neurons.
AB  - Expressions of nerve growth factor (NGF) and low affinity p75 NGF receptor (p75
      NGFR) in gerbil hippocampal neurons after 3.5-min transient forebrain ischemia
      were studied. Most hippocampal CA1 neurons were lost (neuronal density = 44 +/-
      12/mm) at 7 days after recirculation, while no cell death was found in the sham
      control neurons (220 +/- 27/mm). NGF immunoreactivity was normally present in the
      sham-control hippocampal neurons. However, it decreased in hippocampal CA1
      neurons, and slightly decreased in the neurons of CA3 and dentate gyrus areas
      from 3 hr after recirculation. By 7 days, NGF immunoreactivity returned almost
      completely to the sham-control level in the CA3 and dentate gyrus neurons but
      decreased markedly in the CA1 neurons. In contrast, p75 NGFR immunoreactivity was
      scarcely present in the sham-control hippocampal neurons but was induced from 1
      hr after recirculation in the CA1 and CA3 neurons and from 3 hr in the dentate
      gyrus. At 7 days, p75 NGFR immunoreactivity was expressed greatly in the
      surviving CA1 neurons and the reactive astrocytes but was not seen in the other
      hippocampal neurons. The markedly decreased NGF and greatly induced p75 NGFR
      immunoreactivity found in the CA1 neurons after transient forebrain ischemia
      suggests that NGF and p75 NGFR may be involved in the mechanism of delayed
      neuronal death.

PMID- 7563250
TI  - Early neuroblasts are pluripotential: colocalization of neurotransmitters and
      neuropeptides.
AB  - This study was undertaken in order to establish the presence of pluripotential
      neuroblasts in the developing chick CNS. This has been suggested by our previous
      observations that expression of emerging neuronal phenotypes in the chick embryo
      CNS is affected by exposure to neurotrophic substances (i.e., GHRH, SRIF, NGF,
      EGF, muscle-derived factors) or neurotoxins such as ethanol. We have proposed
      that one mechanism whereby these substances elicit their effects is by shifting
      phenotypic expression in populations of pluripotential neuroblasts. In order to
      establish the presence of significant populations of pluripotential neuroblasts,
      cultures obtained from 3-day-old whole chick embryos (E3WE) were double-stained
      with antibodies to markers specific for four neuronal phenotypes in various
      permutations. Cultures at 6 DIV were tested for the presence of tyrosine
      hydroxylase (TH), choline acetyltransferase (ChAT), gamma-aminobutyric acid
      (GABA), and somatostatin (SRIF) alone, and in various combinations. We observed a
      colocalization of all phenotypic markers within neuronal perikarya and processes
      in more than fifty percent of neuronal cells in these cultures. These data
      suggest that developing neuroblasts at this stage of embryogenesis possess the
      machinery necessary to adopt multiple neuronal phenotypes. The colocalization of
      neurotransmitter proteins in early neuroblasts (60 hr of embryogenesis) supports
      the recent concept that these substances themselves may influence phenotypic
      expression and also supports our idea that microenvironmental factors (i.e.,
      ethanol, growth factors) provide signals which affect emerging phenotypes.

PMID- 7563252
TI  - Growth and development.

PMID- 7563251
TI  - Differential regulation of bcl-2, bax, c-fos, junB, and krox-24 expression in the
      cerebellum of Purkinje cell degeneration mutant mice.
AB  - Purkinje cell degeneration (pcd) is an autosomal recessive mutation in the mouse
      characterized by an almost complete loss of cerebellar Purkinje neurons between
      postnatal days 22 and 28. The pcd gene has not been identified, however, a
      relationship between activation of specific genes and cell death has been
      suggested in other models of neuronal cell death. In the present study we
      analyzed the expression of several candidate cell death effector genes (bax, c
      fos, junB, krox-24) and a cell death repressor gene (bcl-2) in the cerebellum of
      pcd homozygotes and wild-type mice. At postnatal day 22, when Purkinje cells
      start to degenerate, levels of c-fos, junB, and krox-24 mRNA increased about 5
      fold in mutants. To the contrary, the amount of bcl-2 mRNA declined and bax
      transcripts remained unchanged compared to wild-type animals. Immunoreactivity
      for c-Fos and Jun could be detected exclusively in cerebellar Purkinje neurons of
      pcd mice but not in wild-types, whereas the number of Bcl-2 immunopositive
      Purkinje cells decreased significantly in mutants. Both double labeling
      experiments and immunostaining of consecutive sections revealed lack of
      colocalization of Jun with Bcl-2. These results demonstrate an induction of
      members of the fos and jun family and a downregulation of antiapoptotic bcl-2 in
      cerebellar Purkinje neurons that are destined to die. Fos and Jun transcription
      factor proteins may be implicated in the regulation of bcl-2 expression and in
      the signal cascade leading to Purkinje cell death.

PMID- 7563253
TI  - Frequency of schistosomiasis mansoni, of its clinicopathological forms and of the
      ectopic locations of the parasite in autopsies in Belo Horizonte, Brazil.
AB  - The frequency of schistosomiasis mansoni, of its clinicopathological forms, and
      of the distribution of Schistosoma mansoni eggs in ectopic locations in each
      clinicopathological form were studied in 1863 complete consecutive autopsies
      performed in Belo Horizonte, Brazil, in the period from 1971 to 1990. Three
      hundred and thirteen cases of S. mansoni infection (16.8%) were found. The
      intestinal form was the most frequent (67.4%), followed by the hepatosplenic form
      without pulmonary hypertension (24.9%). The intestinal form showed a smaller
      number of ectopic sites and a lower percentage of involvement of these sites
      compared to the more severe forms, particularly the hepatosplenic form with
      pulmonary hypertension. The distribution of the frequency of schistosomiasis
      mansoni cases, of the clinicopathological forms of the disease, and of the
      ectopic sites of S. mansoni eggs over the decades considered showed a marked
      reduction in all of these parameters, particularly in the more severe forms.
      These findings can be explained only by earlier diagnosis of the disease and the
      greater efficacy of the specific chemotherapy used today, preventing progression
      to the more severe forms of the parasitosis.

PMID- 7563254
TI  - Efficacy of a 3-day oral regimen of quinine in an area of northern Nigeria with
      low-grade resistance of Plasmodium falciparum to chloroquine and sulphadoxine
      pyrimethamine.
AB  - The efficacy in vivo of a 3-day oral regimen of quinine (30 mg/kg/day) was
      assessed in 34 children with falciparum malaria in an area of northern Nigeria
      with previously documented low-grade parasite resistance to chloroquine and
      sulphadoxine-pyrimethamine (SDX/PYR). By day 4, all 34 children were free of
      parasites. Mean parasite clearance time and fever clearance time were 2.7 and 1.7
      days, respectively. However, on day 14, 5 (14.7%) children were again
      parasitaemic and 4 of them were clinically ill. They were again treated
      successfully with a standard course of oral chloroquine. No adverse drug effects
      were recorded. Of the 34 children, 9 parasite isolates were successfully cultured
      in vitro. EC50 and EC99 were 14.0 and 126.0 pmol per well respectively,
      indicating decreased parasite sensitivity but no resistance in vitro. In
      conclusion, the 3-day course of quinine was found to be an effective alternative
      to standard chloroquine treatment in the study area.

PMID- 7563256
TI  - Scorpion envenomation in children in southern India.
AB  - The clinical presentation of 32 children with scorpion envenomation was analysed.
      The most common presentation was cold, clammy extremities with normal blood
      pressure. Myocarditis was present in 16 children (50%) and encephalopathy in four
      (12.5%). Two children died. ECG was a sensitive indicator of myocarditis which
      was subclinical in four children. Left ventricular dysfunction was a transient
      phenomenon. Myocarditis and encephalopathy were the two lethal complications
      observed. Serum free fatty acid levels were elevated two to three-fold in all
      symptomatic patients. Blood glucose levels were only mildly elevated and serum
      amylase levels and electrolytes were normal in all the children. No specific
      antivenom was given. In the absence of specific antivenom, early and active
      supportive treatment reduces the morbidity and mortality due to scorpion
      envenomation.

PMID- 7563255
TI  - Takayasu's arteritis in Kuwait.
AB  - The present study describes the epidemiological profile and clinical features of
      Takayasu's arteritis (TA) in Kuwait, as well as its association with other
      autoimmune diseases and primary hypercoagulable states. Thirteen patients were
      included from its start on 1 January 1989 till 30 June 1994. Diagnosis of TA was
      established by angiographic studies. Twelve patients were Arabs and 7 were
      Kuwaiti nationals. Five patients were males and renal disease secondary to
      isolated involvement of the abdominal aorta (TA, type II) was the main
      presentation in 4 patients. Coagulation tests were performed in 7 patients and
      included antiphospholipid antibody (aPL) assay as well as protein S, protein C
      and antithrombin III activity. Only one manifested recurrent thrombosis and
      laboratory tests confirmed the presence of a hypercoagulable state secondary to
      aPL and protein S deficiency. Serological tests of systemic lupus erythematosis
      (SLE) were positive in this patient. These data indicate that TA is not a rare
      disease in the Arabic population. In our study, female predominance was not a
      common feature of TA and renal disease secondary to TA type II disease was
      commonly encountered. The association of TA with SLE and primary hypercoagulable
      states was not a consistent finding in our patients with TA, and hence, the
      proposed role for thrombotic vasculopathy in the pathogenesis and progression of
      this disease was unfounded.

PMID- 7563257
TI  - Descriptive features of Dientamoeba fragilis infections.
AB  - A total of 237 cases of Dientamoeba fragilis were identified by a state public
      health laboratory in 1985 and 1986. Dientamoeba fragilis was the only parasite
      found in about two-thirds of the cases. Compared to Giardia cases diagnosed in a
      similar time period, D. fragilis occurred more frequently in females and in
      children 5-9 years old; it was also more likely to be detected in spring and
      summer months. Giardia occurred more frequently in children 0-4 years old.
      Seventy-nine per cent of 70 interviewed D. fragilis cases reported symptoms
      associated with infection; nearly 80% had diarrhoea or loose stools. Interviewed
      cases reported more household and non-household exposure to children 5-9 years
      old than children of other ages. The difference in age and sex distribution of D.
      fragilis and Giardia cases may be related to the life cycle and mode of
      transmission of the two protozoans.

PMID- 7563258
TI  - Paragonimus mexicanus pericarditis: report of two cases and review of the
      literature.
AB  - The cases of two Costa Rican children with pericarditis due to Paragonimus
      mexicanus are reported. Clinical, epidemiological and laboratory tests are
      consistent with the disease. Treatment with praziquantel and bitheonol was
      associated with clinical cure. A review of the literature and a suggested table
      of diagnostic criteria are included.

PMID- 7563259
TI  - Deltamethrin impregnated bednets for the control of urban malaria in Kumba Town,
      South-West Province of Cameroon.
AB  - This study was conducted from January to December 1992 in Kumba, a town situated
      in the rain forest region of the South-West Province of Cameroon, and consisted
      of a longitudinal survey including parasitological and clinical studies. Forty
      households were chosen for the study and randomly divided into two groups, each
      with approximately 240 inhabitants aged < or = 15 years. One group received
      deltamethrin impregnated bednets and the other group had no nets (control). For
      the months of April, June and August (rainy season), deltamethrin impregnated
      bednets did not reduce malaria prevalence significantly, but the overall malaria
      prevalence for all months of the study was significantly reduced (chi 2 MH =
      9.17, P = 0.002). Enlarged spleen rates (chi 2 MH = 6.73, P = 0.009) and spleen
      sizes (P = 0.0002) were also significantly reduced by the nets. However, the
      reduction in the geometric mean parasite density (GMPD) was not significant. Even
      though some of these reductions were statistically significant, they were
      relatively low in a global context compared with previous work done mainly in
      rural areas. In an urban environment, parents and children usually stay up late,
      and probably receive many mosquito bites before going to sleep.

PMID- 7563260
TI  - Cyclospora cayetanensis associated with watery diarrhoea in Peruvian patients.
AB  - Acid-fast, coccidian-like bodies (Cyclospora cayetanensis) were identified over
      the last 18 months in the stools of seven Peruvian patients suffering from
      diarrhoea. The follow-up of two patients revealed a watery, self-limited
      diarrhoea, which lasted for up to four weeks. The organism was simultaneously
      identified in the diarrhoeal stools of three members of the same family who drank
      unchlorinated canal water and in the stools of a duck bred by this family. The
      organism was not found in the faecal samples of 50 healthy subjects and 10 ducks
      bred by families without known diarrhoea cases. These findings, albeit
      preliminary, may be suggesting that besides consumption of untreated water,
      additional modes of transmission such as contact with domestic animals may be
      important in this disease. Further studies are needed to assess whether this
      disease behaves as a zoonotic condition and to ascertain the relative importance
      of symptom-free subjects in person-to-person transmission of the organism.

PMID- 7563261
TI  - Rabies viral antigen in human tongues and salivary glands.
AB  - Lingual and major salivary tissue samples from three cases of rabies were stained
      with the immunoperoxidase (ABC) technique. All tissue blocks had been embedded in
      paraffin 4-10 years before. The first antibody used was monoclonal antirabies
      nucleocapsin (N) mouse antibody (HAM). Four out of five pieces of tongue from two
      cases showed a large amount of granular staining indicating rabies antigen (RVAg)
      inside serous glandular cells, terminal nerves, muscle cells and covering
      epithelial cells including taste cells. In the tissue probes from the third case
      only minimal granular staining was found, probably due to complete absence of the
      serous gland. In contrast to the tongue, only a little weakly reacting material
      was found in 4 out of 9 probes of salivary gland, either in acini or in nerve
      fibres. The amount of RVAg is evidently much greater in the human tongue than in
      major salivary glands, whereas major salivary glands from infected dogs, foxes
      and skunks reportedly contain much RVAg. As the human tongue's serous gland
      appears to be a preferred location for RVAg, it may be a source of oral
      infection.

PMID- 7563262
TI  - An epidemiological investigation of the first outbreak of rhinosporidiosis in
      Europe.
AB  - Until January 1992 rhinosporidiosis was unknown in the Balkans. The outbreak
      which took place at that time in northern Serbia (Yugoslavia) affected 17 people
      over a period of less than two years. The number of patients in this epidemic
      exceeded the total number of autochthonous cases of rhinosporidiosis ever
      recorded in Europe. The male-to-female ratio was 10:7 and, except for a middle
      aged man, all patients were in the age range 6-16 years. Preponderance of ocular
      (12) over nasal (5) localization of the disease in this epidemic indicates that
      the real number of cases may be much higher. The only experience all patients had
      in common was that they spent their holiday preceding the onset of symptoms
      bathing in the same accumulation of stagnant water (the Silver Lake). A case
      control study showed that the odds of being exposed to that particular
      environment by chance were extremely remote.

PMID- 7563264
TI  - Characterization of group A streptococci isolated in Kuala Lumpur, Malaysia.
AB  - T-agglutination patterns of 190 strains of group A streptococci isolated between
      January 1989 and December 1993 from body fluids (10), throat culture (56), pus
      (51) and skin lesions (73) were determined. Mucoid colonial morphology was
      exhibited by 6.3% (12/190) of the strains on initial isolation. Type T-5,11,27,44
      comprised 23.7%, followed by T-1,3,13,B3264 (11.1%), T-4,6 (8.4%) and T-8,25, Imp
      19 (7.9%). About 42% (80/190) strains could not be characterized by T
      agglutination pattern. T-typing of 71 selected strains at WHO Collaborating
      Center, Minneapolis yielded similar results. Nineteen selected strains were
      further characterized by M-typing; only three strains were M-typeable. These
      strains were isolated from throat (M1), sputum (M5) and pus (M12). About 68%
      (48/71) isolates produced serum opacity factor. These data support the existence
      of as yet uncharacterized group A streptococcal serotypes in this region.

PMID- 7563263
TI  - Urban to rural routes of HIV infection spread in Ethiopia.
AB  - A descriptive survey to identify routes of spread of HIV infection from urban to
      rural populations was carried out in a rural south-central Ethiopian district.
      High risk practices for HIV infection and transmission were first documented
      among rural residing former soldiers, merchants and students. Extramarital
      intercourse during the previous 3 months was reported by 45-50% of these
      subgroups. In 25-37%, intercourse with an urban commercial sex worker (CSW) was
      reported and condom use varied from 10 to 30% among subgroups. The perceived risk
      for AIDS was low and changes in risk behaviours were minimal. Next, 502 rural
      males farmers were surveyed. An extramarital sexual contact in the past 3 months
      was reported by 13.5%, with 7% reporting their most recent contact with an urban
      CSW. Only 6% of farmers reported using condoms. Awareness of AIDS was reported by
      59% and, of these, only 28% perceived they were vulnerable. In this study
      increased knowledge was associated with more frequent high risk sexual practices.
      It is concluded that the spread of AIDS into rural communities is occurring as a
      result of the high frequency of high risk sexual behaviours in specific rural
      residing subgroups which frequently travel into urban communities in combination
      with a low background prevalence of high risk practices among the general male
      farmer population.

PMID- 7563266
TI  - The pattern of malignant lymphoma in Oman.
AB  - The pattern of malignant lymphoma (ML) in the Middle East has not been well
      documented and constitutes a lacuna in the epidemiology of this disease. This
      preliminary report describes a retrospective study of 46 native Omanis who, at
      the Sultan Qaboos University Hospital and the Royal Hospital, Sultanate of Oman,
      were diagnosed in 1990 as having ML. Of the 46 patients with ML, 16 (35%) were
      found to have Hodgkin's disease (HD) and 30 (65%) had non-Hodgkin's lymphomas
      (NHL). Among the HD, mixed cellularity (MC) appeared in 9 cases (56%). Among the
      NHL, 25 (83%) showed a diffuse pattern and 5 (17%) were follicular. Twenty-one
      (70%) of the NHL were of high-grade type, of which 5 (17%) were Burkitt-like
      lymphomas. Immunological study of the NHL biopsies revealed 24 (80%) of the B
      cell type, 2 (7%) of the T-cell type, 1 (3%) of the null cell type and 3 (10%)
      could not be classified because of scanty material or unsatisfactory fixation. We
      present in this study the pattern of ML in Oman, which was found to be different
      from those reported from the West, Far East and Saudi Arabia, with some
      resemblance to the pattern from tropical Africa.

PMID- 7563265
TI  - Human T-lymphotropic virus type-I, and hepatitis A, B and C viruses in Nepal: a
      serological survey.
AB  - In 1987, 676 blood samples were collected from inhabitants of the Bhadrakali and
      Kotyang villages in Nepal. The samples were tested for the prevalence of antibody
      to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to
      hepatitis B core antigen (anti-HBc), second-generation antibody to hepatitis C
      virus (anti-HCV) and antibody to human T-lymphotropic virus type-I (anti-HTLV-I).
      Anti-HAV was present in 99.3% of the people surveyed. The prevalence of anti-HAV
      reached 100% in the < 25 age group and was as high or only slightly lower in all
      other age groups. The prevalence of HBsAg was 0.3% and of anti-HBc 7.7%. Anti-HCV
      was found in 0.1% of the residents. No significant difference by gender or
      village was noted in the prevalence of anti-HAV, HBsAg, anti-HBc, or anti-HCV. No
      anti-HTLV-I-positive persons were identified. These data suggest that the
      prevalence of hepatitis B and C virus infections in Nepal is low in contrast to
      hepatitis A virus infection, and that human T-lymphotropic type-I infection may
      be absent in this population.

PMID- 7563267
TI  - Acute rhinocerebral mucormycosis caused by Rhizopus arrhizus from Sri Lanka.
AB  - Rhinocerebral mucormycosis is a rare fungus infection reported mainly from the
      United States of America and Europe. The disease is caused by zygomycete fungi,
      most often by a Rhizopus species. Diagnosis is often made post-mortem and in many
      instances culture identification of the fungus responsible has not been
      performed. A case of culturally proven rhinocerebral mucormycosis is described
      for the first time in Sri Lanka. The patient was a 56-year-old male who had been
      treated for diabetes mellitus for 17 years. He had typical symptoms of numbness
      and loss of sensations over the temporal region, followed by loss of vision and
      proptosis, all on the right side of his face. The diagnosis of rhinocerebral
      mucormycosis was confirmed by microscopic examination and culture of material
      obtained from the retro-orbital space. The patient died before effective
      antifungal therapy could be instituted.

PMID- 7563268
TI  - Acute bronchiolitis.

PMID- 7563269
TI  - Predicting hypoxia in children with acute lower respiratory infection: a study in
      the highlands of Papua New Guinea.
AB  - Pneumonia accounts for nearly half of all admissions amongst children less than 5
      years of age to health centres and hospitals in the highlands of Papua New
      Guinea. Until recently, the indications for the use of oxygen in the management
      of childhood pneumonia in Papua New Guinea had been confined to the detection of
      cyanosis and restlessness. Oxygen is, however, difficult to deliver to many parts
      of Papua New Guinea, leading to high transport costs and shortages. Health
      workers in rural areas are continually faced with decisions as to which children
      should be given oxygen when it is in short supply. This study related clinical
      signs to the oxygen saturation of the blood using a pulse oximeter, in order to
      offer rational criteria for the use of oxygen in health centres and hospitals in
      remote areas. Data were collected on 110 children who were admitted to Tari
      Hospital with a diagnosis of moderate or severe pneumonia. Following admission,
      assessments were repeated at 12-hourly intervals until the child was discharged
      from the intensive nursing ward. All clinical assessments and oximetry readings
      were taken by a registered nurse. A rule developed via quadratic discrimination
      analysis was able to correctly classify 80 per cent of children as having
      adequate/inadequate oxygen saturation, with 'inadequate oxygen saturation'
      defined as less than 85 per cent. This, however, involved a complicated equation
      which would not be suitable for general use in a developing country. The use of a
      'clinical score' using a summation of the major clinical signs was not found to
      offer any advantage over the recognition of any one of four 'indicator'
      signs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563270
TI  - Red cell genetic disorders and plasma lipids.
AB  - To study the plasma lipid levels in patients with red cell genetic disorders, we
      investigated 400 normal individuals, 100 sickle cell disease (SCD) patients, 220
      sickle cell heterozygotes (Hb AS), and 100 individuals suffering from glucose-6
      phosphate dehydrogenase (G-6-PD) deficiency. Whole blood samples were used for
      the determination of haematological parameters and red cell indices, and plasma
      was used for the estimation of plasma lipids using Autoanalyser American Monitor
      'Parallel'. Haemoglobin types in the haemolysates were separated by
      electrophoresis and G-6-PD activity was determined using kits from Boehringer
      Mannheim GmbH. The results from males and females were analysed separately. In
      each group cholesterol levels were slightly higher in the male population, while
      the reverse was true for triglyceride. Sickle cell disease patients had
      significantly (P < 0.05) lower cholesterol level compared to the normal
      individuals. In the Hb AS and G-6-PD deficient groups no significant differences
      were encountered. Multiple regression analysis between cholesterol and
      haematological parameters showed a statistically significant positive correlation
      (P < 0.01) between plasma cholesterol and total haemoglobin in each group,
      particularly in the sickle cell disease patients. The results suggest that
      increased utilization or decreased production may account for the lower
      cholesterol level in severely anaemic patients, particularly those with sickle
      cell anaemia.

PMID- 7563271
TI  - Infection with hepatitis viruses (B and C) and human retroviruses (HTLV-1 and
      HIV) in Saudi children receiving cycled cancer chemotherapy.
AB  - Serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV), human T
      cell lymphotropic virus type 1 (HTLV-1), and human immunodeficiency viruses (HIV
      1 and HIV-2) were studied in 53 Saudi children (31 males, 22 females; 1-12 years
      of age) receiving cycled cancer chemotherapy and in 168 healthy Saudi children
      taken as control. Exposure to HBV in the patients was similar to that in the
      control (6 per cent HBsAg in patients v. 7 per cent in the control; 19 per cent
      exposure rate in patients v. 20 per cent in control). None of our patients was
      vaccinated against HBV prior to chemotherapy. The fact that among the 10 HBV
      exposed patients five patients were anti-HBs-positive is in favour of vaccinating
      Saudi oncology patients against HBV prior to chemotherapy. In contrast to the
      situation with HBV the prevalence of anti-HCV in the patients (11 per cent) was
      significantly higher than that in the control (1 per cent) (P = 0.003). None of
      our patients or the control were anti-HTLV-1 or anti-HIV-positive. The results of
      this study stress the need for an awareness of HCV problem in Saudi oncology
      patients. Strict measures of screening blood donors for all blood-borne viruses
      and, in particular, for HCV in addition to the use of disposable equipment in
      management of cancer patients are items that should be implemented as soon as
      possible.

PMID- 7563272
TI  - The effect of routine hospital care on the health of hypothermic newborn infants
      in Zambia.
AB  - A prospective cohort study was carried out at the University Teaching Hospital,
      Lusaka, Zambia, to investigate the prevalence of neonatal hypothermia, type of
      infant care and incidence of mortality. Two-hundred-and-sixty-one infants, aged 0
      7 days, admitted to the pediatric unit during the 'warm' season were recruited to
      the study. Forty-four per cent of the infants were hypothermic (< 36 degrees C)
      on admission, and admission hypothermia correlated to admission weight and home
      delivery in the youngest age group (0-24 hours). Exclusively breastfed infants
      (age group 1-7 days) were less likely to be hypothermic at admission.
      'Hypothermia' was not recorded as an admission diagnosis and no special attention
      was given to those infants in terms of clinical management. Mean time to reach a
      body temperature above 35.9 degrees C did not differ between infants kept in a
      cot and in an incubator. Total numbers of death was 82 (31 per cent) and the
      mortality was higher in infants who were hypothermic at admission compared to
      those who were not. This study demonstrates that a change of existing care
      routines is needed.

PMID- 7563273
TI  - Concurrent evaluation of immunization programme by Lot Quality Assurance
      Sampling.
AB  - The current EPI methodology for identifying immunization coverage is simple and
      easy to carry out under field conditions and gives a good idea about immunization
      coverage. However, it is not useful for local managers. It does not identify
      small health units with poor performance. Information on performance at the local
      level is vital to enhance overall immunization coverage. Estimation of coverage
      on a small area basis can be made by Lot Quality Assurance Sampling (LQAS). LQAS
      was used in nine sub-centres of district Saharanpur. The methodology was found to
      be feasible and identified seven sub-centres with poor current performance.
      Although LQAS may not be a good substitute for current EPI methodology to
      evaluate immunization coverage in a large administrative area, it is suggested
      that LQAS is a useful additional method for routine monitoring and evaluation of
      health programmes on a small area basis, especially as the overall coverage
      increases.

PMID- 7563274
TI  - Defective clonidine-induced growth hormone secretion and normal thyroid and
      adrenal functions in prepubertal children with chronic renal insufficiency (CRF).
AB  - We evaluated clonidine-induced growth hormone (GH) secretion, insulin-like factor
      I (IGF-I), free thyroxine (FT4), and thyroid stimulating hormone (TSH)
      concentrations, basal (8-h) as well as adrenocorticotrophic hormone (ACTH)
      provoked cortisol secretion in 14 prepubertal children suffering from chronic
      renal failure (CRF) with impaired statural growth [growth velocity (GV) = 3.7 +/-
      0.3 cm/year] and compared these values with those of 10 normal age matched
      children with normal variant short stature (NVSS) (GV = 4.6 +/- 0.4 cm/year). The
      body mass indices and the bone age delay did not differ between the two groups
      (14.8 +/- 0.7 kg/m2 and 1.5 +/- 0.35 years v. 13.8 +/- 0.48 kg/m2 and 2 +/- 0.25
      years, respectively). The basal GH concentrations in CRF patients (4.1 +/- 0.8
      micrograms/l) were significantly higher than those for the NVSS group (1.56 +/-
      0.2 micrograms/l). The peak GH response to clonidine was significantly lower in
      children with CRF (8.4 +/- 1.7 micrograms/l) v. (19.6 +/- 2.3 micrograms/l) for
      the control group (P < 0.01). Eight out of the 14 children with CRF did not mount
      a proper GH response (> 10 micrograms/l) to clonidine stimulation whereas the GH
      response of all the children with NVSS was above 10 micrograms/l. IGF-I
      concentrations were higher in patients with CRF (35.6 +/- 10.9 IU/l) compared to
      those for the NVSS group (22.1 +/- 4.9 IU/l). However, the difference was not
      statistically significant. There was no significant difference in the FT4, TSH as
      well as basal (8-h) and ACTH-stimulated cortisol concentrations between the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563275
TI  - Glucose-6-phosphate dehydrogenase deficiency and sickle cell genes in Bisha.
AB  - This study was conducted on 820 Saudi males and females from Bisha in the western
      province of Saudi Arabia. Blood samples were analysed to determine the frequency
      of glucose-6-phosphate dehydrogenase deficiency and haemoglobin S (Hb S) genes,
      and to investigate interactions between the two genes. Severe G-6-PD deficiency
      in this population was due to G-6-PD-Mediterranean; the African variant G-6-PD-A-
      was not detected. The normal and common form of the enzyme was G-6-PD-B+,
      occurring at a frequency of 0.8444 and 0.8177 in males and females, respectively.
      Variants included G-6-PD-A+, G-6-PD-Mediterranean, and G-6-PD-Mediterranean-like
      at frequencies of 0.0043, 0.0767, and 0.0746, respectively, in males and 0.0057,
      0.05413, and 0.0855, respectively, in females. Sickle cell haemoglobin (Hb S) was
      encountered in the homozygous (4 per cent) and heterozygous (10 per cent) states
      at a gene frequency of 0.0860. No interaction between G-6-PD deficiency and Hb S
      gene was observed. A severe haematological and clinical presentation of the Hb SS
      disease was encountered in the children from Bisha.

PMID- 7563276
TI  - Serum vitamin A (retinol) concentrations and association with respiratory disease
      in premature infants.
AB  - Vitamin A has been shown to be important in immunity and in differentiation of
      epithelial tissues. Serum concentrations of vitamin A (retinol) were measured at
      birth, in 54 preterm and 24 full term infants. Vitamin A concentrations were
      significantly lower in the preterm compared to the full term infants (9.81 +/-
      0.58 micrograms/dl v. 15.58 +/- 1.00 micrograms/dl, P = 0.0001). Serum retinol
      and birth weight were positively correlated (r = 0.39, P = 0.0004); however,
      there was no correlation between maternal and infant vitamin A concentrations.
      The initially reduced vitamin A levels in the preterm infants were not associated
      with respiratory distress syndrome or pneumonia.

PMID- 7563277
TI  - Maternal behaviour and socio-economic influences on the bacterial content of
      infant weaning foods in rural northern Thailand.
AB  - The bacterial contamination of infant weaning foods was examined in the context
      of a longitudinal study of lactation and infant growth, the Chiang Mai Lactation
      Study. Sixty-two mother-infant pairs were selected by random sampling from a
      rural area outside the city of Chiang Mai and studied for 48 hours in their homes
      on six occasions over the first year of life. Data on food hygiene practices and
      maternal factors were related to the total bacterial count per gram and coliform
      content of weaning foods. Bottle feeding, premastication, and mashing were
      significantly related to an increased bacterial content of weaning foods, while
      boiling foods to make soups, preparing in and feeding from a banana leaf, and
      using boiled water to prepare foods all reduced their bacterial content. Storage
      also increased the bacterial contamination in foods and foods were more highly
      contaminated in the rainy season. Maternal age and education were also related to
      some feeding practices. By promoting the feeding of traditional, but less
      contaminated weaning foods, an intervention is put forward which would aim to
      reduce weaning food contamination and thereby reduce incidence of diarrhoea in
      this area of Northern Thailand.

PMID- 7563278
TI  - Algorithm for managing a baby with dusky soles.
AB  - We have been using dusky colour of the sole in newborns as proxy to cyanosis. An
      algorithm for management of dusky soles was developed presupposing that a baby
      can have dusky soles due commonly to hypothermia, hypoxaemia, or hypotension in
      isolation or in combination. Fifty-one consecutive babies were managed according
      to a predetermined algorithm based largely on clinical signs. Forty babies were
      covered by these three broad groups and 37 of them could be managed successfully.
      Of the remaining babies two were found to have congenital malformations on
      autopsy and one died of hyperthermia. Algorithmic approach has simplified the
      management with low failure rate and can be useful when hi-tech neonatal care is
      unaffordable.

PMID- 7563279
TI  - Filarial antibody detection in suspected occult filariasis in children in an
      endemic area.
AB  - A study was conducted in filarial endemic area for diagnosis of occult filariasis
      in various clinical conditions in children. Thirty-five age- and sex-matched
      controls (endemic-15, non-endemic-10, disease control-10), 16 classical lymphatic
      filariasis, and 92 occult filariasis (clinical conditions which fall in the
      spectrum of occult filariasis and suspected to be filarial), were subjected to
      peripheral night blood smear examination for microfilaria (mf) and stick ELISA
      test using mf ES antigen for filarial antibodies. In the control group none
      showed mf and only 3 per cent (1/35) among endemic control were positive for
      filarial antibodies. In classical filariasis 1 per cent (2/16) showed mf and 94
      per cent (15/16) had filarial antibodies. In suspected occult filariasis 1 per
      cent (one case of arthritis) showed mf and 62 per cent (57/92) showed filarial
      antibodies. These consisted of tropical pulmonary eosinophilia 63 per cent
      (15/24), arthritis where no cause could be ascertained on investigation 64 per
      cent (27/42), nephrotic syndrome 69 per cent (11/16), acute glomerulonephritis
      with ASO < 200 units 38 per cent (3/8), and cardiomyopathy 50 per cent (1/2).
      Correlation with age showed that 80 per cent (4/5) of cases of arthritis seen in
      0-4 years of age group and 82 per cent (11/9) of nephrotic syndrome in the 10-14
      years of age group were positive for filarial antibody. Arthritis due to other
      causes and minimal change nephrotic syndrome are uncommon in these respective age
      groups. It is concluded that the role of filariasis in endemic areas in these
      disease states cannot be denied and needs to be studied further.

PMID- 7563280
TI  - New information on the composition of bint al Dhahab, a mixed lead monoxide used
      as a traditional medicine in Oman and the United Arab Emirates.
AB  - X-ray diffraction and X-ray micro-analyser studies of the traditional medicine
      bint al dhahab confirm that it is composed of two polymorphs of lead monoxide
      (PbO). These studies also show the presence of cadmium and a third complex
      monoxide of lead containing antimony. Bulk analyses show that the substance
      contains approximately 91 g of lead monoxide, 600 mg of antimony oxide, and 50 mg
      of cadmium per 100 g of bint al dhahab. This new information may assist
      physicians to devise appropriate treatment regimens for patients presenting with
      symptoms of toxicity.

PMID- 7563282
TI  - Pediatric treatment costs and the HIV epidemic.

PMID- 7563281
TI  - Shortcomings in the pharmacotherapy of epileptic children in Bombay, India.
AB  - In 108 epileptic children referred for Therapeutic Drug Monitoring (TDM), 60 (56
      per cent) had epilepsy for over 2 years. At first estimation among 79 (73 per
      cent) children on monotherapy, only three out of 23 on phenytoin, 20 out of 31 on
      phenobarbitone, and 15 out of 25 on carbamazepine had plasma levels within the
      therapeutic range. After TDM, only nine (8 per cent) were advised to continue the
      original prescription. Only 35 (32 per cent) followed up beyond 6 months and 15
      (14 per cent) who benefited had a significantly shorter duration of epilepsy
      before referral (P < 0.001). Eventually, 12 (11 per cent) followed up beyond 2
      years, and five (5 per cent) had achieved a probable cure. The study highlights
      the urgent need for setting up TDM clinics for epileptic children in India.

PMID- 7563283
TI  - Use of arm circumference (AC) measurement and maternal reporting of illness.

PMID- 7563284
TI  - Salmonella gastroenteritis in young children: a clinical study.

PMID- 7563285
TI  - The coordination and consistency of rowers in a racing eight.
AB  - Recordings of force developed simultaneously by four rowers in a good club
      standard eight over a 20-min training run were analysed in terms of mean and
      variability. The average force-time profiles showed small but distinctive
      differences between rowers that were maintained as force declined through the
      run. The variability was examined further in terms of time-series of features
      extracted from single force-time profiles, including the peak force, duration and
      interstroke interval. There were consistent positive correlations between rowers
      in interstroke intervals even after removal of low-periodicity components
      (trends) in the time-series.

PMID- 7563286
TI  - An evaluation of instrumented tank rowing for objective assessment of rowing
      performance.
AB  - The aim of this study was to evaluate instrumented tank rowing for its ability to
      measure objectively the individual performance components of power output and
      rowing skill in a sample of collegiate rowers. The measuring system utilized
      strain gauges and a potentiometer to measure force on the oar and its angular
      position at each sampling interval. Power outputs were calculated for 13
      collegiate rowers tested individually during a 30-s bout of maximal work. Results
      from this 'tank test' were compared with power measurements from both Concept II
      (CII) and Stanford rowing ergometers and from a Wingate test, using similar 30-s
      bouts of maximal work. Significant differences (P < 0.05) were found between the
      tank test and all other modes of testing except the Wingate test for average
      power. These differences can probably be attributed to the different methods of
      power measurement and to the different skill-dependence associated with the
      tests. For each subject, peak power and average power per stroke were measured
      from the rowing tests. The CII and Stanford test data for all subjects were
      correlated with their tank test data. Similar correlations were made between tank
      data and the peak and mean power from the Wingate test. The strongest correlation
      was in peak power measurements with the Wingate test (r = 0.92, P = 0.0001).
      Instrumented tank rowing provided objective information on individual power
      output unique from rowing and cycling ergometry. Of the various tests, the tank
      test appeared to provide better and more complete power data specific to rowing.
      This method also provided objective data for interpreting various aspects of
      rowing skill, including oar handling, technical efficiency, consistency, stroke
      frequency, stroke recovery ratio and stroke length. Instrumented tank rowing has
      substantial potential as a coaching tool or as a self-training device for
      improving rowing ability.

PMID- 7563287
TI  - Cellular immune activity in response to increased training of elite oarsmen prior
      to Olympic competition.
AB  - This study investigated the changes in urinary neopterin, a biochemical marker of
      cellular immune activity, in elite male rowers undertaking a progressive increase
      in training prior to Olympic competition. Twenty-seven male rowers of the 1992
      Great Britain team provided daily urine samples for a 4-week period of training
      that included 17 days of altitude training and 10 days of heat acclimatization.
      The mean (+/- S.D.) ratio of neopterin/creatinine in urine increased from pre
      training values of 135 +/- 32 to a peak of 219 +/- 121 mumol neopterin per mol
      creatinine on day 19 of training (P < 0.05). Changes in the ratio of
      neopterin/creatinine with training were found to be transient and highly variable
      between subjects, ranging from no change to peak values five-fold greater than
      baseline. On the basis of the in vivo measurement of cell-mediated immunity
      employed in this study, we conclude that elite athletes engaged in high-intensity
      training prior to competition show either no change or a moderate increase in
      cellular immune activation.

PMID- 7563289
TI  - The application of modern methods of biomechanics to the evaluation of jumping
      performance in ancient Greece.
AB  - Modern methods of biomechanics are applied to examine some of the outstanding
      feats of jumping that have been reported in the literature from classical times.
      It is concluded that these feats could not have been achieved using the current
      long-jump prescription, with the take-off and landing areas in the same
      horizontal plane. A possible explanation is that the landing area was some 5.5 m
      or more below the take-off area. Alternatively, and more plausibly, the jump
      could have been similar to the modern triple jump.

PMID- 7563288
TI  - Do selected kinanthropometric and performance variables predict injuries in
      female netball players?
AB  - The aim of this study was to determine which kinanthropometric and performance
      variables predict injuries in female netball players. In a prospective study, 72
      volunteer grade A netball players (mean age 20.6 +/- 3.6 years, range 15-36
      years) were measured for hypermobility, somatotype, static balance, jumping
      abilities and anaerobic fitness at the University of Western Australia Human
      Movement Performance Laboratory prior to the start of their 14-week season.
      Injuries were classified by site, diagnosis and severity, and were monitored
      throughout the entire season by the same physiotherapist at the Western Australia
      (WA) Matthews Netball Centre, Perth, Australia. A total of 22 injuries in 22
      players were recorded, affecting the ankle joint lateral ligament complex (59%),
      knee ligaments (18%), back (18%) and Achilles tendon (5%). Injuries were more
      common among grade A1 players than other grades (54 vs 19%, P < 0.001). Within
      grade A1 players, the proportion of injuries decreased with age (P < 0.05).
      Players were more likely to have had an injury if they had better jumping
      ability, better anaerobic fitness and if they were low on the endomorphy
      somatotype scale (P < 0.05). After allowing for both jumping ability and
      endomorphy, there was no longer a significant difference between A1 and non-A1
      players in their risk for injury. Young elite players are at a substantially
      increased risk of injury. This higher risk appears to be associated with--if not
      a direct consequence of--their being thinner, fitter and having more powerful
      jumping capabilities. This suggests that injury-prevention programmes should be
      targeted at elite players, especially the younger ones.

PMID- 7563290
TI  - The use of artificial intelligence in the analysis of sports performance: a
      review of applications in human gait analysis and future directions for sports
      biomechanics.
AB  - Computers have played an important supporting role in the development of
      experimental and theoretical sports biomechanics. The role of the computer now
      extends from data capture and data processing through to mathematical and
      statistical modelling and simulation and optimization. This paper seeks to
      demonstrate that elevation of the role of the computer to involvement in the
      decision-making process, through the use of artificial intelligence techniques,
      would be a potentially rewarding future direction for the discipline. In the
      absence of significant previous work in this area, this paper reviews experiences
      in a parallel field of medical informatics, namely gait analysis. Research into
      the application of expert systems and neural networks to gait analysis is
      reviewed, observations made and comparisons drawn with the biomechanical analysis
      of sports performance. Brief explanations of the artificial intelligence
      techniques discussed in the paper are provided. The paper concludes that the
      creation of an expert system for a specific well-defined sports technique would
      represent a significant advance in the development of sports biomechanics.

PMID- 7563291
TI  - Performance prediction for Olympic kayaks.
AB  - This paper sets out the effects of the various factors which determine the speed
      of racing kayaks and canoes, with the aim of identifying the areas most likely to
      lead to improvements. The friction, wave and aerodynamic components of hull drag
      are first described in terms of the hull parameters, in order to provide accurate
      predictions of propulsive power as a function of hull speed. The generation of
      thrust by paddling is described via the mechanics of vortex-ring wakes, in order
      to determine the propulsive efficiency in terms of the parameters describing the
      blade and stroke. Equating the thrust and drag then leads to reliable estimates
      of the mechanical power actually delivered by a canoeist. The earlier analysis
      then leads to a predictive model for hull speed in terms of all the parameters
      describing the hull and blade performance. This is used to determine the
      sensitivity of hull speed to small changes in each parameter, enabling the most
      important factors to be identified. The paper concludes with a discussion of the
      various improvements to kayaks that have actually appeared in recent years, and
      uses the earlier analysis to explain and predict the resulting speed changes.

PMID- 7563292
TI  - Examining warm-up decrement as a function of interpolated open and closed motor
      tasks: implications for practice strategies.
AB  - Warm-up decrement (WUD) is a loss in the level of physical performance following
      rest and prior to subsequent trials. The activity-set hypothesis is one of
      several explanations for this phenomenon. The purposes of this study were to
      field test the efficacy of the activity-set hypothesis and explore the
      effectiveness of performing closed and open interpolated tasks in reducing WUD.
      The criterion task was hitting tennis ground strokes in response to a ball
      tossing machine, an open skill. Elite players (n = 20) from a tennis club in New
      South Wales, Australia, practised either a closed or open task, or rested, prior
      to resuming the first post-rest trial, using a repeated-measures design. The
      results yielded partial support of the activity-set hypothesis. Although the
      closed interpolated task markedly reduced WUD, open skill practice solicited
      better post-rest performance. Warm-up decrement was clearly evident under the
      rest condition. Furthermore, post-rest scores were statistically superior for the
      open skill condition as compared to practising a closed interpolated task, at
      least for the first two post-rest trials (trials 21 and 22). The implications for
      these results in reducing WUD are explored within the frameworks of task
      classification systems and schema theory.

PMID- 7563293
TI  - Fluid intake in male and female runners during a 40-km field run in the heat.
AB  - To compare physiological responses, hydration status and exercise performance in
      similarly trained men and women in a hot, humid environment, 12 highly trained
      runners were studied during a simulated 40-km race. A 7% carbohydrate-electrolyte
      (CE) beverage was consumed prior to exercise (400 ml) and every 5 km
      (approximately 250 ml) during the run. The run times of the males and females did
      not differ significantly (173.5 +/- 8.5 and 183.8 +/- 4.2 min, respectively); nor
      did the rate of fluid intake relative to body mass (10.3 +/- 0.7 and 10.7 +/- 0.8
      ml kg-1 h-1, respectively) or percent body mass loss (4.0 +/- 0.1% and 3.9 +/-
      0.1%, respectively). During the run, %VO2 max, heart rate, concentrations of
      blood lactate, serum total protein and plasma osmolality were also similar for
      both groups. However, some significant sex differences (P < 0.05) were observed:
      the females had lower plasma volume losses and higher serum potassium and sodium
      concentrations than the males during the run. Rectal temperatures were lower in
      the female runners compared with the males during the last 10 km of the run (0.7
      degrees C) and recovery (1.1 degrees C). Findings from this 40-km field run in
      hot, humid conditions suggest that CE fluid replacement at a relatively similar
      dosage (approximately 10 ml kg-1 h-1) may have sex-specific physiological
      effects. These observations warrant further investigation to assess the need for
      sex-specific fluid replacement guidelines.

PMID- 7563294
TI  - The relationship between critical power and running performance.
AB  - Critical power is a theoretical concept that presumes there is a certain work
      rate which may be maintained without exhaustion. The extent to which critical
      power predicts running performance over varying distances has not been
      determined, and so the aim of this study was to correlate measurements of
      critical power in the laboratory to running performances in the field at 40 m and
      1, 10 and 21.1 km in a group of .17 male long-distance runners (mean +/- S.D. age
      = 31.7 +/- 7.3 years). Each subject ran to exhaustion on the treadmill in the
      laboratory at six different speeds, ranging from 17 to 25 km h-1. Least squares
      analyses were used to fit an exponential decay to the relationship between the
      running speed (y) versus time to exhaustion (x). Critical power was calculated as
      the running speed (y) coinciding with the asymptote or C parameter of the y =
      A.e(-Bx) + C relationship. The VO2 max was also measured in all subjects. For the
      data in the field, each subject was timed over 40 m and 1 km and participated in
      10- and 21.1-km races. The mean critical power of the subjects in this study was
      18.5 +/- 1.6 km h-1. The test-retest correlation coefficient for the
      determination of critical power was r = 0.99. The mean VO2 max, measured in a
      progressive exercise protocol starting at 13 km h-1 and increasing by 1 km h-1
      every minute, was 59.2 +/- 4.6 ml O2 kg-1 min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563295
TI  - Normal uterine arterial blood flow in postmenopausal women assessed by
      transvaginal color Doppler ultrasonography.
AB  - We used transvaginal color Doppler sonography to study uterine artery blood flow
      velocity waveforms in 345 normal postmenopausal women who had never been on
      hormone replacement therapy. Our objective was to establish the standard baseline
      flow values for normal postmenopausal women. The mean pulsatility index was 3.38
      +/- 1.04 and the mean resistive index was 0.93 +/- 0.09. There was a positive
      correlation between arterial blood flow impedance and number of years since
      menopause. We believe that these levels may become important screening parameters
      for the detection of endometrial carcinoma in postmenopausal women.

PMID- 7563298
TI  - Quantitative comparison of two distinct echogenic structures appearing on the
      same image using gain-assisted densitometric evaluation of sonograms (GADES).
AB  - Gain-assisted densitometric evaluation of sonograms with two distinct echogenic
      structures appearing on each image was performed to establish if their density
      gain setting curves have similar inclinations. We used the breast model (n = 67)
      in which hyperechoic masses were compared to the surrounding hyperechoic tissue
      at the optimal gain (Gopt) and at Gopt + 5. Both structures had significantly
      different film-corrected densities and showed a linear decline of density as the
      system gain increased from Gopt - 5 to Gopt + 5. The least squares regression
      lines were almost parallel. The density-gain unit decrease from Gopt - 5 to Gopt
      was not different, but the decrease from Gopt to Gopt + 5 reached statistical
      significance. The data suggest that skewed values are theoretically possible in
      comparing two distinct echogenic structures. However, within the gain intervals
      used in GADES, these differences are negligible and comparisons are as accurate
      as with the assessment of a single echogenic structure.

PMID- 7563297
TI  - Transvaginal color Doppler assessment of endometrial status in normal
      postmenopausal women: the effect of hormone replacement therapy.
AB  - We used transvaginal color Doppler sonography to study the effects of hormone
      replacement therapy on the endometrial structure and vascular flow of 345 normal
      postmenopausal women. We studied women taking estrogen replacement alone,
      continuous combined estrogen and progestogen, and estrogen followed sequentially
      by estrogen-progestogen combination. Endometrial measurements prior to the
      initiation of hormone replacement therapy were used as baseline values. An
      increase in endometrial thickness was seen soon after initiation of hormone
      replacement therapy (P < 0.0001). Hyperplasia or adenocarcinoma was found only
      when endometrial thickness was greater then 9 mm. No correlation was found
      between hormone replacement therapy and the occurrence of endometrial hyperplasia
      or adenocarcinoma.

PMID- 7563296
TI  - Normal uterine arterial blood flow in postmenopausal women assessed by
      transvaginal color Doppler sonography: the effect of hormone replacement therapy.
AB  - We used transvaginal color Doppler sonography to study the effect of hormone
      replacement on the uterine arterial blood flow for 203 postmenopausal women. The
      regimens studied involved estrogen replacement alone, continuous combined
      estrogen and progestogen, and estrogen followed sequentially by combined estrogen
      progestogen. The mean pulsatility index fell to 65% +/- 9% and the mean resistive
      index fell to 87% +/- 4% of baseline during the first month of therapy (P <
      0.0001). The addition of a progestogen did not alter the effect of estrogen alone
      (P > 0.5). Our findings suggest that the increase in vascular flow occurs even in
      women who begin therapy long after menopause.

PMID- 7563299
TI  - Prenatal sonographic predictors of liver herniation in congenital diaphragmatic
      hernia.
AB  - We conducted a retrospective review of prenatal sonograms of all fetuses (n = 25)
      with left sided congenital diaphragmatic hernia undergoing in utero surgical
      repair of the defect at the University of California, San Francisco, Fetal
      Treatment Center. Sixteen candidates were selected for analysis to determine
      reliable predictors of liver herniation. Bowing of the umbilical segment of the
      portal vein (portal sinus) to the left of midline and coursing of portal branches
      to the lateral segment of the left hepatic lobe toward or above the diaphragmatic
      ridge were the best predictors for liver herniation into the fetal thorax
      (positive predictive values of 85% and 100%, respectively). The stomach position
      was a good predictor if observed in a posterior or midthoracic location (positive
      predictive value = 100%). However, this occurred in only 7 of 16 (44%) cases.
      Visibility of the right lung was less informative (positive predictive value =
      63%). We do not recommend in utero primary closure of congenital diaphragmatic
      hernia when there is sonographic evidence of liver herniation into the fetal
      thorax.

PMID- 7563300
TI  - Color Doppler sonography of adnexal torsion.
AB  - The purpose of this study was to describe the color Doppler sonographic findings
      in adnexal torsion that distinguish viable from nonviable ovaries. We present the
      color Doppler sonographic features in 13 patients with surgically proved adnexal
      torsion that help determine whether or not the ovaries were viable or nonviable
      at the time of surgery. Eleven combined ovarian and tubal torsions and two
      isolated tubal torsions were studied. In 10 cases the ovaries were considered
      nonviable at the time of surgery and in three cases they were considered viable.
      Of the nonviable group, six showed absent arterial and venous flow centrally, but
      two had low velocity (< 5 cm/s) arterial flow peripherally in the region of the
      adnexal branch of the uterine artery or in the main ovarian artery, and two
      demonstrated absent or reversed diastolic arterial flow. None of the nonviable
      ovaries showed venous flow centrally. In contrast, all of the viable ovaries
      demonstrated venous flow centrally, and two had peripheral and central arterial
      flow. Although the CDS findings in adnexal torsion are variable, ovarian
      viability may be predicted if central venous flow is present.

PMID- 7563301
TI  - Transvaginal pulsed and color Doppler sonography for the evaluation of
      adenomyosis.
AB  - In an earlier paper, we reported our scoring system for the diagnosis of
      adenomyosis by gray scale transvaginal sonography. In this study we evaluated 44
      benign uterine masses (adenomyosis and myomas) and seven uterine malignancies. We
      used transvaginal color and pulsed Doppler imaging to determine whether this
      technique is useful to differentiate adenomyosis from uterine malignancies. The
      peak systolic velocity and the resistive index of intratumoral vessels were
      studied. The differences in these parameters for adenomyosis and uterine
      malignancies were statistically significant. Our results suggest that this
      technique is useful to differentiate adenomyosis from uterine malignancies.

PMID- 7563303
TI  - Sonographic diagnosis of a corpus callosum lipoma with extracranial extension in
      an infant.

PMID- 7563302
TI  - Early prenatal diagnosis of bronchopulmonary sequestration with associated
      diaphragmatic hernia.

PMID- 7563304
TI  - Nephrogenic diabetes insipidus: a cause of severe nonobstructive urinary tract
      dilatation.

PMID- 7563305
TI  - The prenatal ultrasonographic visualization of imperforate anus in monoamniotic
      twins.

PMID- 7563306
TI  - Acrania.

PMID- 7563307
TI  - Sonographic manifestation and Doppler blood flow study in fetal triploidy
      syndrome: report of two cases.

PMID- 7563309
TI  - High expression of a CD38-like molecule in normal prostatic epithelium and its
      differential loss in benign and malignant disease.
AB  - PURPOSE: We characterize an undescribed antigen on prostatic epithelial cells,
      which is recognized by anti-CD38. MATERIALS AND METHODS: Normal (3 cases), benign
      hyperplastic (10) and carcinomatous (10) prostatic tissues were analyzed using
      immunohistochemistry, immuno-electron microscopy and the Western blot test.
      RESULTS: Comparison of prostatic and lymphatic CD38 antigen revealed identical
      bands at 45 kD. Electron microscopy demonstrated anti-CD38 reactivity on the
      cytoplasmic membrane and within the secretory vacuoles. Double labeling with anti
      cytokeratin types 5/15 and 8/18 confirmed that basal and secretory normal
      prostatic epithelial cells express CD38. By contrast, a complete loss was found
      in malignant (52.8%), tumor-surrounding nonmalignant (16.3%) and benign prostatic
      hyperplasia derived glands (3.7%). CONCLUSIONS: CD38 is a novel prostatic
      antigen. Its role in intracellular calcium mobilization may contribute to smooth
      muscle cell contraction and/or sperm motility.

PMID- 7563308
TI  - Percutaneous management of transitional cell carcinoma of the renal collecting
      system: 9-year experience.
AB  - PURPOSE: We establish the effectiveness of percutaneous resection of transitional
      cell carcinomas of the renal collecting system. MATERIALS AND METHODS: A
      retrospective analysis was done of 36 kidneys treated during a 9-year period.
      Adjunctive therapy with bacillus Calmette-Guerin was given in 19 cases. RESULTS:
      Of 36 kidneys 6 were treated by immediate nephroureterectomy for aggressive
      disease, leaving 30 units treated by a complete course. The recurrence rate was
      33%, which varied with histology as specific recurrence rates for grades 1 to 3
      tumors (18%, 33% and 50%, respectively). The only cancer related mortalities
      occurred with grade 3 tumors. These tumors also had a higher incidence of
      understanding and vascular complications. Bacillus Calmette-Guerin therapy showed
      no significant improvement in survival. CONCLUSIONS: With vigilant followup,
      percutaneous management of transitional cell carcinoma of the renal collecting
      system is an acceptable alternative to nephroureterectomy in patients with grade
      1 disease, grade 2 disease who are at risk for renal insufficiency and medical
      contraindications to a major open operation.

PMID- 7563310
TI  - Combination finasteride and flutamide in advanced carcinoma of the prostate:
      effective therapy with minimal side effects.
AB  - PURPOSE: The efficacy of the combination of finasteride and flutamide in select
      patients with advanced prostatic cancer is determined. MATERIALS AND METHODS: A
      total of 22 sexually active patients with stages C and D1 carcinoma of the
      prostate was treated with finasteride plus flutamide. Mean followup was 22
      months. RESULTS: Initial mean prostate specific antigen level was 42.9 ng./ml. At
      3 and 6 months, the mean prostate specific antigen level was 3.6 ng./ml. and 2.9
      ng./ml., respectively. The results appear durable at 24 months. Side effects were
      minimal, with 86% of the men maintaining sexual function. CONCLUSIONS:
      Finasteride plus flutamide should be considered in sexually active patients with
      minimal volume advanced prostate cancer.

PMID- 7563311
TI  - Spontaneous unilateral adrenal hemorrhage: computerized tomography and magnetic
      resonance imaging findings in 8 cases.
AB  - PURPOSE: We report and discuss the imaging features of 8 cases of spontaneous
      unilateral adrenal hematomas, a rare lesion. MATERIALS AND METHODS: Computerized
      tomography (CT) was done in 8 cases, magnetic resonance imaging (MRI) in 5, and
      CT and MRI in 5. Imaging findings were reviewed and correlated with histological
      findings in all 8 cases. RESULTS: MRI was the most accurate imaging modality and
      showed variable appearances. On pathological evaluation the hematomas were old
      and organized. No contrast enhancement was noted on CT or MRI. CONCLUSIONS: One
      must not consider the diagnosis of spontaneous adrenal hematoma only as
      superimposed on a phechromocytoma or malignant lesion in the case of an
      incidentally discovered large adrenal mass with normal biological findings. MRI
      signs of adrenal hemorrhage and the failure of enhancement of such a mass should
      strongly suggest adrenal hematoma.

PMID- 7563312
TI  - Adrenalectomy via the dorsal approach: a benchmark for laparoscopic
      adrenalectomy.
AB  - PURPOSE: We reviewed our experience with posterior surgical excision of
      aldosteronomas. MATERIALS AND METHODS: A retrospective review identified 40
      consecutive cases performed by 1 surgeon. RESULTS: Mean patient age was 46 years
      and mean blood loss was 237 cc. There was no perioperative mortality or
      intraoperative complications. Times to unassisted ambulation and return to a
      normal diet were 2.2 and 2.4 days, respectively, with a mean postoperative
      hospital stay of 4.4 days. CONCLUSIONS: The removal of aldosteronomas via the
      dorsal approach is a safe reliable technique with acceptable morbidity. These
      results provide a benchmark by which the results of laparoscopic adrenalectomy
      may be judged.

PMID- 7563313
TI  - Laparoscopic nephropexy: Washington University experience.
AB  - PURPOSE: We evaluated the efficacy of laparoscopic nephropexy for symptomatic
      nephroptosis. MATERIALS AND METHODS: We performed laparoscopic right nephropexy
      in 6 patients who presented with symptomatic nephroptosis documented by
      radiographic studies and/or renal scans. In the first patient Gerota's fascia was
      secured to the peritoneal reflection of the line of Toldt using tacking clips. In
      the subsequent 5 patients the lateral border of the kidney was sutured to the
      overlying fascia of the quadratus lumborum muscle using an intracorporeal
      suturing technique. Additionally, the superior edge of the incised infrahepatic
      triangular ligament was sutured to the anterior mid portion of the renal capsule,
      thereby creating a vertical and horizontal means of fixation. RESULTS:
      Laparoscopic right nephropexy was successful in all 6 patients. Average operative
      time was 4 hours. All patients resumed oral intake during postoperative day 1.
      Average parenteral analgesia requirement postoperatively was 42.7 mg. morphine.
      Hospital stay averaged 2.5 days and patients returned to usual activities an
      average of 2.5 weeks postoperatively. Postoperative imaging studies confirmed a
      decrease in or resolution of nephroptosis in all patients. All patients remained
      asymptomatic for an average of 11 months (range 2 to 30). CONCLUSIONS:
      Laparoscopic nephropexy appears to be a feasible treatment option for patients
      with symptomatic, documented nephroptosis. The procedure can be accomplished
      safely and effectively with satisfactory anatomical and clinical results.

PMID- 7563314
TI  - Ureteroscopy in pregnancy.
AB  - PURPOSE: We report our experience with ureteroscopy in pregnancy. MATERIALS AND
      METHODS: From 1984 to 1994, 24 pregnant women with lasting symptoms of ureteral
      obstruction underwent diagnostic and therapeutic ureteroscopy. Most of the women
      were in the second or third trimester of gestation. RESULTS: A rigid ureteroscope
      was introduced easily to the upper third of the ureter or into the renal pelvis
      in all patients. Ureteral calculi were extracted in 13 cases. There were no
      serious complications. CONCLUSIONS: Ureteroscopy is a safe procedure that may be
      used to diagnose and extract obstructing ureteral calculi during pregnancy when
      conservative measures fails.

PMID- 7563315
TI  - New approaches to old diseases.

PMID- 7563317
TI  - Gout and stones or stones and gout?

PMID- 7563316
TI  - Clinical and biochemical presentation of gouty diathesis: comparison of uric acid
      versus pure calcium stone formation.
AB  - PURPOSE: We compared gouty diathesis with uric acid versus calcium stones.
      MATERIALS AND METHODS: We retrospectively reviewed clinical and laboratory data
      from 95 gouty diathesis patients (28 with uric acid and 67 with calcium stones)
      and 99 normal subjects. RESULTS: Of the gouty diathesis patients gouty arthritis
      was present in 21% of those with uric acid and 12% of those with calcium stones.
      Hyperuricemia developed in 43% of those with uric acid and 27% of those with
      calcium stones, and 2% of controls. Urinary pH was independent of the net
      gastrointestinal absorption of alkali in the gouty diathesis groups. Urinary pH
      and citrate increased after potassium citrate treatment. CONCLUSIONS: The
      characteristic features of primary gout were present in both gouty diathesis
      groups and both are responsive to treatment.

PMID- 7563318
TI  - Extracorporeal shock wave lithotripsy in 5 patients with aortic aneurysm.
AB  - PURPOSE: The safety and efficacy of extracorporeal shock wave lithotripsy (ESWL*)
      in patients with an aortic aneurysm were assessed. MATERIALS AND METHODS: Five
      patients with an aortic aneurysm and symptomatic renal (4) or upper ureteral (1)
      lithiasis underwent ESWL with either an HM3 or HM4 lithotriptor. RESULTS: The
      procedure was well tolerated in all patients. The stone was fragmented completely
      in the 4 patients with renal lithiasis, while 1 with ureteral lithiasis also
      required ureteroscopic extraction of the stone fragments. CONCLUSIONS: For
      patients with symptomatic renal stones and an aortic aneurysm ESWL may be the
      treatment of choice.

PMID- 7563319
TI  - Long-term radiographic and functional outcome of extracorporeal shock wave
      lithotripsy induced perirenal hematomas.
AB  - PURPOSE: We determined the long-term radiographic and functional outcome of
      extracorporeal shock wave lithotripsy (ESWL) related perirenal hematomas.
      MATERIALS AND METHODS: We followed 19 patients with 21 ESWL induced hematomas for
      4 to 61 months (mean 19.6) after ESWL with serial ultrasound, blood pressure and
      serum creatinine determinations. RESULTS: Complete radiographic resolution of the
      hematoma was evident in 18 cases (85.7%), while 2 (9.5%) were significantly
      smaller and 1 (4.8%) remained unchanged. Of 10 patients who were normotensive
      before ESWL none experienced sustained new onset hypertension. Of 9 patients with
      preexisting hypertension none had a sustained exacerbation. Finally, during
      followup serum creatinine levels overall remained unchanged from pre-ESWL values.
      CONCLUSIONS: We conclude that, by far, the most likely outcome for patients with
      ESWL related hematomas is spontaneous radiographic resolution within 2 years
      without clinically evident adverse effects on blood pressure or renal function.

PMID- 7563320
TI  - Intraoperative sonography for the evaluation and management of renal tumors:
      experience with 100 patients.
AB  - PURPOSE: Intraoperative sonography was used to evaluate prospectively the renal
      parenchyma of patients undergoing surgery for presumed renal neoplasia. MATERIALS
      AND METHODS: One surgeon (F.F.M.) evaluated 100 kidneys using a triple-head
      sector ultrasonic transducer (5 MHz., 7.5 MHz. and 10 MHz. with duplex Doppler
      imaging). The size, number, echo texture, location, and relationship of suspected
      lesions to the collecting system, vasculature and renal capsule were recorded.
      Real-time Doppler imaging was used to distinguish among renal arteries, renal
      veins and the collecting system. Sonography was used to delineate the extent of
      the tumor and presence or absence of satellite lesions. All patients were
      evaluated preoperatively with abdominal computerized tomography. RESULTS: Under
      ultrasonic guidance partial nephrectomy was done in 40 cases, radical nephrectomy
      in 56, unroofing of renal cysts in 3 and renal biopsy in 1. Of the patients 8
      were considered candidates for partial nephrectomy but underwent radical
      nephrectomy after intraoperative sonography revealed more extensive tumor,
      especially at the renal hilum. Similarly, 3 patients with a suspected malignancy
      were spared nephrectomy after intraoperative sonography and frozen section
      analysis revealed benign multilocular cysts. All surgical margins after
      sonographic evaluation were negative in patients undergoing partial nephrectomy.
      CONCLUSIONS: Intraoperative ultrasound is a useful adjunct for the dynamic
      evaluation of renal tumors in the surrounding environment of renal cysts, the
      collecting system and the renal vasculature. It is particularly beneficial in
      defining preoperative indeterminate renal lesions and in evaluating extrarenal
      structures for tumor involvement, such as the renal vein, inferior vena cava,
      adrenal gland and liver. Intraoperative sonography is most useful during partial
      nephrectomy and may improve tumor-free surgical margins. Sonography is routinely
      used during partial nephrectomy.

PMID- 7563322
TI  - Gasless laparoscopy-assisted nephrectomy without tissue morcellation for renal
      carcinoma.
AB  - PURPOSE: The efficacy of gasless laparoscopy-assisted nephrectomy for renal
      tumors is determined. MATERIALS AND METHODS: Seven patients with renal tumors
      underwent gasless laparoscopy-assisted nephrectomy. The results were compared to
      those of patients undergoing open nephrectomy. RESULTS: Although a long operating
      time was required, convalescence was significantly more rapid. En bloc removal of
      the kidney and complete pathological examination were possible in all patients.
      CONCLUSIONS: This procedure may be useful for the treatment of noninvasive renal
      carcinoma, especially in patients with cardiovascular and/or ventilatory
      complications. However, long-term followup is necessary to confirm the efficacy
      in preventing recurrence.

PMID- 7563321
TI  - Vein invasion in renal cell carcinoma: impact on metastatic behavior and
      survival.
AB  - PURPOSE: The development of a thrombus extending into the veins is well
      recognized in renal cell carcinoma. We investigated the hypothesis that vein
      invasion alone has no adverse impact on survival but is a highly negative factor
      in other tumors. MATERIALS AND METHODS: In 200 consecutive patients invasion of
      the renal vein and vena cava was evaluated and compared with the clinical course.
      RESULTS: A total of 26 patients had vena caval and 47 had renal vein invasion.
      Patients with venous invasion had a significantly shorter survival but no
      survival difference was demonstrated based on the level of involvement.
      CONCLUSIONS: Our study indicates that vein invasion itself seems to be an
      important prognostic factor in renal cell carcinoma.

PMID- 7563323
TI  - Nucleolar organizer regions: a new prognostic factor for upper tract urothelial
      cancer.
AB  - PURPOSE: The prognostic significance of argyrophilic staining in the nucleolar
      organizer regions was studied in 63 patients with primary urothelial tumors of
      the renal pelvis and ureter. MATERIALS AND METHODS: Silver staining of paraffin
      embedded sections was performed using a 1-step technique. RESULTS: The prognosis
      for patients with a mean number of argyrophilic nucleolar organizer region
      proteins per nucleus (argyrophilic nucleolar organizer region score) of 8 or
      greater was significantly worse than that for patients with a score of less than
      8 (P <0.001). CONCLUSIONS: Argyrophilic nucleolar organizer region score is a new
      prognostic factor in primary urothelial tumors of the renal pelvis and ureter,
      and it is particularly useful for patients with invasive tumors.

PMID- 7563324
TI  - Changing trends in the management of iatrogenic ureteral injuries.
AB  - PURPOSE: We evaluated changing trends in the management of late diagnosed
      iatrogenic ureteral injuries before and after the introduction of percutaneous
      nephrostomy. MATERIALS AND METHODS: The study included 44 patients of whom 24
      were treated primarily by immediate reconstructive surgery from 1979 to 1984 and
      20 were treated primarily by percutaneous nephrostomy tube insertion beginning in
      1985. RESULTS: Six of the 24 patients underwent ureteroneocystostomy and 18
      underwent end-to-end uretero-ureteral anastomosis to repair the injury.
      Postoperatively 18 patients had a urinary tract infection. Hospital stay after
      reconstructive surgery ranged from 14 to 35 days (average 18). Long-term followup
      showed a normal upper urinary tract in 22 patients and mild to moderate
      hydroureteronephrosis in 2. Of the 20 patients who underwent percutaneous
      nephrostomy 16 (80%) had complete spontaneous recovery of the injured ureter
      after 14 to 66 days (average 32). Hospital stay after the insertion of the
      percutaneous nephrostomy tube ranged from 3 to 5 days. Urinary tract infection
      developed in 4 patients and mild hydronephrosis was noted in 1 on long-term
      followup. CONCLUSIONS: The primary management of ureteral injury by percutaneous
      nephrostomy resulted in significantly decreased reoperation and morbidity rates,
      and enabled spontaneous recovery of the injured ureter in the majority of
      patients.

PMID- 7563325
TI  - Risk of bowel dysfunction with diarrhea after continent urinary diversion with
      ileal and ileocecal segments.
AB  - PURPOSE: In a retrospective study we evaluated the risk of diarrhea after
      continent urinary diversion using ileal and ileocecal segments. MATERIALS AND
      METHODS: We interviewed 100 patients of whom 65 underwent ileal and 35 underwent
      ileocecal resection. RESULTS: Of the 65 patients who underwent ileal resection 7
      (11%) and of the 35 who underwent ileocecal resection 8 (23%) reported chronic
      diarrhea of greater than 6 months in duration, which subsided spontaneously in 2
      patients in each group. In each group 3 patients responded well to cholestyramine
      treatment and 3 responded to loperamid or psyllium. Two patients with ileocecal
      resection failed to respond to drug therapy. CONCLUSIONS: The risk of diarrhea
      after ileocecal resection seems to be twice as high as after ileal resection.
      Most patients responded to symptomatic drug therapy. Alternative surgical
      therapies should be considered when risk factors are present.

PMID- 7563327
TI  - Combination chemotherapy with intra-arterial cisplatin and doxorubicin plus
      intravenous methotrexate and vincristine for locally advanced bladder cancer.
      Kyushu University Urological and Radiological Oncology Group.
AB  - PURPOSE: We evaluate the usefulness of neoadjuvant chemotherapy for bladder
      cancer. MATERIALS AND METHODS: The usefulness of neoadjuvant, modified
      methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy was evaluated
      in 36 patients with locally advanced bladder cancer. RESULTS: Of 36 patients 12
      achieved a clinical complete response and 17 had a partial response. Of the 12
      patients who achieved a clinical complete response the bladder was preserved in
      11 and all patients were disease-free at a median of 33 months. No significant
      toxicity was observed. CONCLUSIONS: This chemotherapy is useful for locally
      advanced bladder cancer and the feasibility of bladder preservation in patients
      with a clinical complete response was suggested.

PMID- 7563326
TI  - Early and late cystometry of detubularized and nondetubularized intestinal
      neobladders: new observations and physiological correlates.
AB  - PURPOSE: We studied the volume and pressure changes with time in detubularized
      and nondetubularized neobladders. MATERIALS AND METHODS: Cystometry was performed
      at early and late followup in 54 male patients with post-cystectomy intestinal
      neobladders constructed from an intact ileocecal segment in 33, detubularized
      sigmoid in 11 and detubularized ileum in 10. RESULTS: With time the capacity of
      the neobladder increased in all 3 groups. Concomitantly, while intact ileocecal
      bladders showed an increase in intra-reservoir pressure and persistence of
      involuntary contractions, detubularized sigmoid and ileal bladders showed a
      decrease in intra-reservoir pressure and involuntary contractions. CONCLUSIONS:
      Increased capacity with time is not due to detubularization per se but rather to
      over distension, which is more marked in detubularized (109 to 112%) than in
      tubular (79%) segments. Detubularized intestinal neobladders not only offer a
      high capacity, low pressure and high compliant reservoir but these
      characteristics also are increased with time.

PMID- 7563328
TI  - The prostate involvement as prognostic factor in patients with superficial
      bladder tumors.
AB  - PURPOSE: The prognostic value of prostate involvement in patients with
      superficial bladder cancer was analyzed. MATERIALS AND METHODS: We studied 96
      patients with prostate involvement. Taking progression-free survival rate as an
      end point, univariate and multivariate analyses were done. RESULTS: The presence
      or absence of bladder carcinoma in situ is related to poor and good prognoses,
      respectively (p < 0.001). Stromal invasion (p < 0.001) and pan-urothelial
      involvement (p = 0.03) were also identified as independent factors of poor
      prognosis. CONCLUSIONS: Patients with tumor limited to the mucosa can be treated
      conservatively. Cystoprostatectomy can be performed in patients with ductal
      involvement. The prognosis of patients with stromal invasion is poor despite
      radical treatment.

PMID- 7563329
TI  - Changing age incidence and pathological types of schistosoma-associated bladder
      carcinoma.
AB  - PURPOSE: The changes in certain characteristic features of schistosoma-associated
      bladder carcinoma are determined. MATERIALS AND METHODS: A retrospective study
      was done of patients with schistosoma-associated bladder carcinoma treated
      between 1962 and 1967, and between 1987 and 1992. RESULTS: Mean patient age
      increased from 47 +/- 13.6 to 53 +/- 12.2 years and the male-to-female ratio
      changed from 7.8:1 to 4.9:1. Tumors showed a decreased incidence of nodular
      (58.7% versus 83.4%) and squamous (54% versus 65.8%) cell types, and an increased
      incidence of papillary (34.8% versus 4.3%) and transitional (42% versus 31%) cell
      types. All changes were statistically significant (p < 0.05) and paralleled by an
      increased incidence of low degree schistosomal infestation from 18.6 to 47.8% (p
      < 0.05). CONCLUSIONS: The shift in age incidence and pathological findings
      towards those of nonschistosomal cases could conceivably be attributed to the
      increased incidence of low infestation in recent years. The change in male-to
      female ratio is probably due to more exposure of women to schistosomal
      infestation than has occurred previously.

PMID- 7563330
TI  - Changing concepts on pathology and therapy for transitional cell carcinoma.

PMID- 7563331
TI  - Paclitaxel, cisplatin and methotrexate combination chemotherapy is active in the
      treatment of refractory urothelial malignancies.
AB  - PURPOSE: We investigated the activity of combination chemotherapy consisting of
      paclitaxel, cisplatin and methotrexate in patients with advanced urothelial
      cancers. MATERIALS AND METHODS: A total of 25 consecutive patients with
      metastatic refractory urothelial malignancies was treated with a combination of
      200 mg./m.2 paclitaxel, 30 mg./m.2 methotrexate and 70 mg./m.2 cisplatin in a
      pilot study. RESULTS: There were no complete responses. Of 25 patients 10 (40%),
      including 3 of 7 with liver metastases, had a partial response. Hematological and
      nonhematological toxicity was tolerable. CONCLUSIONS: The combination
      chemotherapeutic regimen of paclitaxel, cisplatin and methotrexate is active in
      patients with advanced urothelial cancer and warrants further study.

PMID- 7563332
TI  - Scrotal flap epilation in urethroplasty: concepts and technique.
AB  - PURPOSE: We describe our technique of scrotal epilation and the advantages of
      using the resultant glabrous scrotal skin in reconstructive urethral surgery.
      MATERIALS AND METHODS: An insulated needle model adapted to scrotal hair
      characteristics and a thermocoagulation current generator were used. RESULTS: An
      average of 3 epilatory sessions with a 4-week interval between treatments was the
      optimal schedule. No cutaneous infection was noted. CONCLUSIONS: The good results
      permitted the conversion of predetermined scrotal zones into wide areas of
      alopecia to be used as excellent skin flaps in complex urethral stenosis surgery
      in postpubertal male patients.

PMID- 7563333
TI  - Preference, compliance and initial outcome of therapeutic options chosen by
      female patients with urinary incontinence.
AB  - PURPOSE: We determined the patient preference for, compliance with and initial
      outcome of either behavioral modification, pharmacotherapy or surgery for urinary
      incontinence. MATERIALS AND METHODS: A total of 150 incontinent women underwent
      basic evaluation based on Agency for Health Care Policy and Research urinary
      incontinence guidelines. Options were presented and the chosen modality was
      evaluated at 4 to 6-week intervals. RESULTS: Of the patients 61% chose behavioral
      modification, 25% chose pharmacotherapy and 14% chose surgery. The dropout rate
      was 33% (50 of 150 women), including mostly those on behavioral modification. Of
      the remaining patients 74% on pharmacotherapy and 73% on behavioral modification
      reported marked improvement. CONCLUSIONS: When given options, patients chose
      nonoperative measures first. Compliance was poor among patients who chose
      behavioral modification.

PMID- 7563334
TI  - The effect of study methodology on reported success rates of the modified Pereyra
      bladder neck suspension.
AB  - PURPOSE: We compared surgical results in a cohort of women after modified Pereyra
      bladder neck suspension using questionnaire based outcomes analysis versus a
      retrospective chart review. MATERIALS AND METHODS: Of 151 patients who underwent
      modified Pereyra bladder neck suspension 102 had complete questionnaire and chart
      data for review. Mean patient age was 56 years and followup was 25 months.
      RESULTS: According to outcomes analysis 48 patients (47.1%) were cured and in 65
      (64%) stress urinary incontinence improved compared to 74 (72%) cured and 89
      (89%) improved by retrospective review. Of the 102 chart review patients 10 (9%)
      reported daily pad use compared to 55 of the 102 (53%) in the questionnaire
      study. CONCLUSIONS: This study controls for patient selection, definition of cure
      and length of followup, and demonstrates that study methodology profoundly
      affects reported outcomes for the modified Pereyra bladder neck suspension.

PMID- 7563335
TI  - Cavernous oxygen tension and smooth muscle fibers: relation and function.
AB  - PURPOSE: We studied the effect of intracavernous oxygen tension on the alteration
      of cavernous smooth muscle fibers in potent and impotent men. MATERIALS AND
      METHODS: Intracavernous oxygen tension (mm. Hg) was measured during flaccidity
      and 10 minutes after intracavernous prostaglandin E1 injection in psychogenic
      control patients, and those with venous leakage and arterial lesions. Cavernous
      biopsies were performed and the percent of smooth muscle fibers was analyzed
      objectively using immunohistochemical actin anti-actin staining. Simultaneously
      brachial oxygen tension (mm. Hg) was measured and the cavernous brachial oxygen
      tension index was then determined. RESULTS: At flaccidity no significant
      difference was noted in oxygen tension values among the 3 groups of patients.
      After prostaglandin E1 injection cavernous oxygen tension and the cavernous
      brachial oxygen tension index in the control group were significantly different
      (p < 0.01) from those of the venogenic and arteriogenic groups (p < 0.01). The
      mean percent of cavernous smooth muscle fibers in the control group was
      significantly different from those of the venous leakage and arterial lesion
      groups (p < 0.01). There was a good correlation between the percent of cavernous
      muscle fibers and the value of oxygen tension before (p < 0.05) and after
      prostaglandin E1 injection (p < 0.01). A similar correlation was noted between
      cavernous muscle fibers and cavernous brachial oxygen tension index in the
      different groups of patients (p < 0.01). CONCLUSIONS: Reduction of the
      intracavernous smooth muscle fibers in impotent patients could be explained by
      low intracavernous oxygen tension.

PMID- 7563336
TI  - Comparison of RigiScan and sleep laboratory nocturnal penile tumescence in the
      diagnosis of organic impotence.
AB  - PURPOSE: We evaluated the relative use of RigiScan measurement of radial rigidity
      compared to sleep laboratory measurement of axial rigidity and trained observer
      determination of erectile function in the diagnosis of organic impotence.
      MATERIALS AND METHODS: A total of 28 patients underwent simultaneous 2-night
      formal sleep laboratory nocturnal penile tumescence and RigiScan monitoring.
      Standard normal values for radial rigidity and axial rigidity were tested for
      accuracy in predicting normal nocturnal penile tumescence compared to trained
      observer determination of the adequacy of an erection for penetration. RESULTS:
      RigiScan tip measurements correlated poorly with buckling pressure, while base
      measurements strongly correlated (p = 0.0005). Observer determination of a
      functional erection was strongly associated with tip (p = 0.002), base (p =
      0.0005) and buckling pressure measurements (p = 0.0005). Using observer
      determination as the gold standard receiver operating curves were generated to
      select RigiScan base and buckling pressure measurements that predicted functional
      erections with the highest sensitivity and specificity. CONCLUSIONS: RigiScan is
      a useful tool for measuring nocturnal penile tumescence. However, base
      measurements are more accurate than tip measurements for evaluating erectile
      function. The currently accepted level of rigidity used to define a normal
      erection (70% or greater) overestimates organic erectile dysfunction.

PMID- 7563337
TI  - A study in patients with erectile dysfunction comparing different formulations of
      prostaglandin E1. Alprostadil Study Group.
AB  - PURPOSE: Prostaglandin E1 sterile powder and sterile solution are 2 new
      formulations of exogenous prostaglandin E1 that are more convenient for auto
      injection therapy for erectile dysfunction than the presently used pediatric
      sterile solution. Therefore, the pharmacodynamic profiles of intracavernous
      prostaglandin E1 sterile powder and nonalcohol sterile solution were compared
      with the pediatric sterile solution in men with erectile dysfunction who were
      known to be stable responders to intracavernous prostaglandin E1. MATERIALS AND
      METHODS: Based on the dose used at home, patients were randomized to 1 of 5 dose
      groups: 0 microgram. (placebo), 2.5 micrograms., 5 micrograms., 10 micrograms. or
      20 micrograms. Each patient received a single injection of the same dose of each
      of the 3 formulations. The primary pharmacodynamic end points were clinical
      evaluation of erectile response, RigiScan real-time evaluation of erectile
      response and patient evaluation of erectile response. RESULTS: No significant
      differences were identified among the formulations for any of these end points,
      either by comparison among all active doses or by comparison at each
      prostaglandin E1 dose level. There was also little or no intra-patient variation
      in dose response and the inter-dose variation in response between patients was
      not significant. Pharmacodynamic end points were well intercorrelated, although
      assessment of erectile response by the patients tended to be more positive than
      that by RigiScan or clinical evaluation. There were no major side effects. Penile
      pain on injection and/or during erection occurred in 9 to 17% of the patients
      according to the formulations. However, penile pain was also reported by 11% of
      the placebo-treated patients. CONCLUSIONS;: The 3 formulations of prostaglandin
      E1 showed equivalence and were safe for the treatment of erectile dysfunction
      with respect to side effects.

PMID- 7563338
TI  - Analysis of immunological alterations associated with testicular prostheses.
AB  - PURPOSE: Recipients of silicone gel filled testicular prostheses were evaluated
      for the possible immunological abnormalities of human adjuvant disease. MATERIALS
      AND METHODS: Medical record audits were performed for 48 recipients of a silicone
      gel filled testicular prosthesis. Seven patients consented to a detailed health
      profile questionnaire, physical examination and serological testing. RESULTS:
      Retrospective chart analyses and physical examinations were unremarkable.
      Serological results and questionnaire responses varied. One patient with signs
      and symptoms suggestive of human adjuvant disease underwent prosthesis removal
      but adjacent tissues had no evidence of silicosis. Long-term followup was poor.
      CONCLUSIONS: Immunological alterations were present in 71.4% of examined
      recipients but they may have been coincidental. Careful followup of recipients of
      a silicone gel filled testicular prosthesis is needed.

PMID- 7563339
TI  - The effect of varicocelectomy on serum testosterone levels in infertile men with
      varicoceles.
AB  - PURPOSE: We evaluated the effect of varicocelectomy on serum testosterone.
      MATERIALS AND METHODS: We retrospectively reviewed the effect of varicocelectomy
      on serum testosterone levels in 53 infertile men with varicoceles. RESULTS: Mean
      serum testosterone increased from a preoperative level of 319 +/- 12 to 409 +/-
      23 ng./dl. postoperatively (p < 0.0004). Men with at least 1 firm testis
      preoperatively had a greater increase in serum testosterone (p < 0.005). An
      inverse correlation was noted between preoperative testosterone levels and change
      in testosterone after varicocelectomy (r = -0.34, p < 0.013). CONCLUSIONS:
      Varicocelectomy can increase serum testosterone for infertile men with
      varicoceles. Although improvement in serum testosterone does not necessarily
      cause a direct improvement in semen quality, varicocelectomy may improve hormonal
      and spermatogenic function.

PMID- 7563340
TI  - Sclerosing Sertoli cell tumor of the testis: a distinct histological subtype.
AB  - PURPOSE: A case of sclerosing Sertoli cell tumor of the testis is reported. The
      histological and clinical features are compared to those of other Sertoli cell
      tumor subtypes. MATERIALS AND METHODS: The current urological and pathological
      literature was reviewed. RESULTS: The tumor was identified incidentally in a 35
      year-old white man. Pathological examination was performed and the patient was
      well at 9 months. CONCLUSIONS: Sertoli cell tumors are heterogeneous and not
      accurately considered a uniform entity. The currently recognized variants differ
      in apparent malignant potential as well as the association with disease processes
      in other unrelated organ systems.

PMID- 7563341
TI  - Improved accuracy of computerized tomography based clinical staging in low stage
      nonseminomatous germ cell cancer using size criteria of retroperitoneal lymph
      nodes.
AB  - PURPOSE: We evaluated the significance of retroperitoneal lymph nodes detected by
      computerized tomography (CT) of low stage nonseminomatous germ cell tumor
      patients. MATERIALS AND METHODS: A blind retrospective review of 143 CTs of low
      stage nonseminomatous germ cell tumor revealed pathological stage A disease on 89
      (62.2%) and pathological stage B disease on 54 (37.8%). A multivariate logistic
      regression model was used to evaluate the relationships between diameter of the
      retroperitoneal nodes detected in these CTs and pathological stage. RESULTS:
      Based on this model, as the diameter of the nodes increased within a 0 to 25 mm.
      range, the likelihood of pathological stage B disease increased in a continuous
      fashion. Using a 3 mm. threshold to define nonmetastatic nodes the sensitivity
      and negative predictive value of CT based staging was 90%. CONCLUSIONS: This
      measurement scheme improves the accuracy of staging compared to conventional
      methods.

PMID- 7563342
TI  - Transition zone index as a method of assessing benign prostatic hyperplasia:
      correlation with symptoms, urine flow and detrusor pressure.
AB  - PURPOSE: Prostate volume has been poorly correlated to various parameters used to
      assess benign prostatic hyperplasia (BPH), including symptoms, peak urine flow
      and detrusor pressure at peak urine flow. The purpose of this study was 2-fold:
      1) to determine if transrectal ultrasound measurement of the transition zone of
      the prostate served as a better proxy for determining prostate size and
      correlated better with American Urological Association symptom score, peak urine
      flow and detrusor pressure, and 2) if the parameter transition zone index (the
      ratio between transition zone volume and prostate volume) was useful in
      evaluating clinical prostatism. MATERIALS AND METHODS: We prospectively evaluated
      61 men with symptomatic BPH (age 64.6 +/- 9.7 years) according to symptoms, peak
      urine flow, pressure/flow analysis, transrectal ultrasound volume of the entire
      prostate and the transition zone, and calculation of the transition zone index.
      RESULTS: Age correlated with symptoms (r = 0.31, p = 0.01) and peak urine flow
      correlated negatively with symptoms and age (p = 0.002). Age also correlated with
      prostate volume (r = 0.54 and p = 0.03) and transition zone (r = 0.31, p = 0.05).
      There was a weak correlation between prostate volume and symptoms, peak urine
      flow and detrusor pressure at peak urine flow; a stronger correlation between
      transition zone and symptoms (r = 0.48, p = 0.03), and peak urine flow (r = 
      0.34, p = 0.05), and a significant correlation (p = 0.001) between transition
      zone index and symptoms (r = 0.75), peak urine flow (r = -0.71) and detrusor
      pressure at peak urine flow (r = 0.43). A transition zone index of greater than
      0.50 was a useful cutoff point and highly significant (p = 0.002) for delineating
      patients with more severe abnormalities of symptoms, peak urine flow and detrusor
      pressure at peak urine flow. CONCLUSIONS: Transition zone index is a parameter
      that correlates significantly with evaluated parameters of BPH and may serve as a
      useful proxy for evaluating worsening obstruction. Studies are underway to
      determine if transition zone index can be used prospectively to predict and
      correlate response with therapies designed to ablate prostatic tissue medically
      or surgically.

PMID- 7563343
TI  - Benign prostatic hyperplasia specific health status measures in clinical
      research: how much change in the American Urological Association symptom index
      and the benign prostatic hyperplasia impact index is perceptible to patients?
AB  - PURPOSE: We assessed the relationship between changes in scores for the American
      Urological Association (AUA) symptom index and benign prostatic hyperplasia (BPH)
      impact index with patient global ratings of improvement in a large Veterans
      Affairs trial comparing different pharmacological therapies for BPH. MATERIALS
      AND METHODS: The primary analyses compared absolute score changes from baseline
      with global ratings of improvement at 13 weeks for 1,218 men. RESULTS: Subjects
      who rated themselves as being slightly improved had a mean decrease in AUA
      symptom index and BPH impact index scores of 3.1 and 0.4 points, respectively.
      However, the baseline scores strongly influenced this relationship. CONCLUSIONS:
      These data provide guidance for investigators using the AUA symptom index and BPH
      impact index as outcome measures.

PMID- 7563344
TI  - Responders and nonresponders to transurethral microwave thermotherapy: a
      multicenter retrospective analysis.
AB  - PURPOSE: We attempted to identify any parameter that could possibly lead to a
      successful treatment outcome after transurethral microwave thermotherapy.
      MATERIALS AND METHODS: Clinical parameters and treatment profiles of 292 patients
      were analyzed in a retrospective multicenter manner. Responder and nonresponder
      groups were identified according to a given definition. RESULTS: No statistically
      significant differences in baseline characteristics were found. Responders showed
      a 76% symptomatic improvement rate compared to 27% in nonresponders, and an 82%
      improvement rate in peak flow compared to a 5% decrease in nonresponders.
      Responders also showed a significantly greater increase in posttreatment PSA
      level and a significantly greater amount of energy released during treatment.
      CONCLUSIONS: No baseline clinical parameter is capable of predicting treatment
      outcome.

PMID- 7563345
TI  - The effects of finasteride on hematuria associated with benign prostatic
      hyperplasia: a preliminary report.
AB  - PURPOSE: The efficacy of finasteride was assessed in the treatment of gross
      hematuria associated with benign prostatic hyperplasia (BPH). MATERIALS AND
      METHODS: A retrospective review was done of 18 patients who had been placed on
      finasteride (5 mg . daily) for the treatment of gross hematuria associated with
      BPH. A hematuria grading system was devised. RESULTS: Of the 12 patients with
      longer than 3 months of followup (mean 14) 11 improved according to the grade of
      hematuria after finasteride therapy. CONCLUSIONS: Finasteride is effective in
      treating hematuria associated with BPH. This finding is especially relevant for
      patients with multiple medical problems and anesthetic risks.

PMID- 7563346
TI  - Benign prostatic hypertrophy--measurement of clinical outcomes.

PMID- 7563347
TI  - A comparative study of transurethral resection of the prostate using a modified
      electro-vaporizing loop and transurethral laser vaporization of the prostate.
AB  - PURPOSE: We determined the relative efficacy of a modification of transurethral
      resection of the prostate using a vaporizing loop (VaporTrode) with transurethral
      laser vaporization of the prostate using the Ultraline fiber. MATERIALS AND
      METHODS: A comparative trial of 58 patients with symptomatic prostatism was
      performed. Parameters evaluated included operative time, postoperative
      catheterization time, American Urological Association (AUA) symptom score, peak
      urine flow and post-void residual urine. RESULTS: Of the 29 patients who
      underwent electro-vaporization AUA symptom score decreased from 15.3 to 5.3 and
      4.9, and peak urine flow increased from 8.2 to 14.9 ml. per second and 15.6 ml.
      per second at 1 and 3 months, respectively (p = 0.01). Of the 29 patients
      undergoing laser vaporization of the prostate AUA symptom score decreased from
      14.7 to 10.1 and 7.6, and peak urine flow increased from 9.7 to 13.7 ml. per
      second and 14.9 ml. per second at 1 and 3 months, respectively (p = 0.025).
      However, there were significant differences in mean catheterization time (electro
      vaporization group 14.7 hours and laser group 79.6 hours, p < 0.001), and cases
      of postoperative irritative symptoms (3 electro-vaporization and 19 laser) and
      retention requiring repeat catheterization (6 laser). CONCLUSIONS: Our early
      clinical experience highlights several potential advantages of electro
      vaporization, particularly the low incidence of postoperative morbidity.
      Currently a multicenter clinical trial is underway to determine the long-term
      efficacy and safety of electro-vaporization as a potential therapeutic modality
      in the treatment of men with symptomatic benign prostatic hyperplasia.

PMID- 7563348
TI  - The incidence of high grade prostatic intraepithelial neoplasia in needle
      biopsies.
AB  - PURPOSE: High grade prostatic intraepithelial neoplasia is the most likely
      precursor of invasive prostate cancer. The identification of prostatic
      intraepithelial neoplasia in needle biopsy specimens warrants repeat biopsy
      because of its high predictive value for cancer. The incidence of prostatic
      intraepithelial neoplasia in contemporary needle biopsies is unknown. MATERIALS
      AND METHODS: To determine the incidence of patients requiring repeat needle
      biopsy because of abnormal findings in needle aspirations (high grade prostatic
      intraepithelial neoplasia and microscopic foci suspicious for but not diagnostic
      of malignancy), we compared the pathological findings in 400 prostatic needle
      biopsies, including 200 consecutive cases from an academic medical center (Mayo
      Clinic) and an equal number from a private practice laboratory (Glendale Memorial
      Hospital and Health Center). RESULTS: The biopsies revealed similar findings from
      the 2 medical centers: benign prostatic tissue in 41.5 to 50% of the cases,
      prostatic intraepithelial neoplasia in 16.5 to 9.5%, foci suspicious for but not
      diagnostic of malignancy in 1.5 to 2.5% and cancer in 40.5 to 38% (Mayo Clinic
      versus Glendale Memorial, respectively). Clinical information was available from
      the 200 Mayo Clinic patients who underwent biopsy, and there was no difference in
      the distribution of findings by digital rectal examination or transrectal
      ultrasound, although the median serum prostate specific antigen concentration was
      higher in patients with prostatic intraepithelial neoplasia and cancer than in
      those with benign biopsies. CONCLUSIONS: High grade prostatic intraepithelial
      neoplasia is a frequent finding in needle biopsies and is present in up to 16.5%
      of the cases. There was no apparent difference in the incidence of prostatic
      intraepithelial neoplasia and cancer between 2 geographically diverse medical
      centers. Up to 18% of patients are candidates for another biopsy based on needle
      biopsy findings of prostatic intraepithelial neoplasia or foci suspicious for but
      not diagnostic of malignancy.

PMID- 7563349
TI  - Prostatic transition zone biopsies in men with previous negative biopsies and
      persistently elevated serum prostate specific antigen values.
AB  - PURPOSE: In men with persistently elevated serum prostate specific antigen (PSA)
      concentrations and prostatic biopsies that show no cancer an important question
      is whether the PSA elevation is caused by undetected cancer in the transition
      zone of the prostate gland. MATERIALS AND METHODS: To evaluate this issue further
      we examined 166 men age 50 years of older who participated in a PSA based
      screening trial for prostate cancer. All men had an initially elevated serum PSA
      concentration of 4.1 ng./ml. or greater. They had undergone 1 or 2 sets of
      negative peripheral zone biopsies of the prostate but elevated serum PSA
      concentrations persisted. They underwent repeat biopsy of the peripheral zone as
      well as 2 core biopsies from the right and 2 from the left transition zone region
      of the prostate. RESULTS: Peripheral and transition zone biopsies revealed cancer
      in 3 of 19 cases (16%). Cancer was present in the peripheral zone only biopsy in
      14 of 19 cases (74%). Two of 19 cancers (10%) were detected only in the
      transition zone. Overall 17 of the 19 cancers (89%) were detected by peripheral
      zone biopsy. CONCLUSIONS: Transition zone biopsy detects few additional prostate
      cancers in men with persistent serum PSA elevations and previous negative
      biopsies.

PMID- 7563350
TI  - Ultrasound guided seminal vesicle biopsies in men with suspected prostate cancer.
AB  - PURPOSE: The histology of ultrasound guided seminal vesicle biopsies is assessed
      and the results are correlated with clinical or pathological stage of prostate
      cancer. MATERIALS AND METHODS: A total of 517 consecutive men underwent bilateral
      (515) or unilateral (2) seminal vesicle biopsy during sextant biopsy of the
      prostate. RESULTS: Seminal vesicle epithelium and muscularis were identified in
      490 of 1,032 biopsy specimens (47%) and smooth muscle consistent with seminal
      vesicle muscularis was identified in 393 (38%). The seminal vesicle biopsy was
      positive for cancer in 7 of 123 patients (6%) with with clinical stages T1c and
      T2 tumors, 27 of 60 (45%) with stages T3 to 4 disease and 9 of 13 (69%) with
      metastatic cancer. Of 39 patients who underwent radical prostatectomy 1 of 36
      (3%) without and 0 of 3 (0%) with seminal vesicle invasion had a positive seminal
      vesicle biopsy. CONCLUSIONS: Seminal vesicle epithelium and muscularis or smooth
      muscle consistent with the seminal vesicle muscularis can be procured in most
      patients using contemporary ultrasound guided biopsy techniques. However,
      apparently false-negative seminal vesicle biopsies are not uncommon and seminal
      vesicle biopsies contribute little to the staging of T1c and T2 tumors.

PMID- 7563351
TI  - Prostate specific antigen in the expressed prostatic fluid of men with benign
      prostatic hyperplasia and prostate carcinoma.
AB  - PURPOSE: We tested the hypothesis that the histochemically demonstrated prostate
      specific antigen (PSA) content of prostate carcinoma cells does not necessarily
      reflect PSA production and secretion by evaluating expressed prostatic fluid.
      MATERIALS AND METHODS: Expressed prostatic fluid and serum from 152 men with
      clinical benign prostatic hypertrophy (BPH), 132 with histologically proved BPH
      and 46 with prostate carcinoma were analyzed with the Hybritech PSA assay.
      RESULTS: Expressed prostatic fluid PSA levels from carcinoma patients (median
      1.70 mg./ml., mean 2.25) were significantly higher than in the histologically
      proved BPH group (median 1.28 mg./ml., mean 1.42, p < 0.05). CONCLUSIONS: PSA
      concentration is increased in the expressed prostatic fluid of prostates of men
      with carcinoma compared to those with histological BPH. This finding may be a
      functional manifestation of a field change or paracrine effects within the
      prostate.

PMID- 7563352
TI  - Prostate cancer.

PMID- 7563353
TI  - Tumor volume and prostate specific antigen: implications for early detection and
      defining a window of curability.
AB  - PURPOSE: We attempted to determine the relationship between tumor volume and
      extent of localized prostate cancer, as well as the interrelationships of tumor
      volume with prostate specific antigen (PSA) level, grade and stage. MATERIALS AND
      METHODS: Serial whole mount sections from 128 patients who underwent radical
      prostatectomy were analyzed using a computer assisted volumetric program.
      Statistical evaluations were performed using logistic and simple regression
      analyses. RESULTS: The median tumor volume for patients with organ confined
      disease was significantly lower than for those with extraprostatic extension
      (1.25 versus 2.94 cc, p < 0.001). A significant incidence (32%) of small volume
      cancers (0.51 to 1.5 cc) exhibited extraprostatic extension while that of
      extraprostatic disease increased to 66% for patients with tumor volumes greater
      than 1.5 cc (p < 0.001). Of men with clinically significant (greater than 0.5 cc,
      or Gleason score 7 or more) pathological stage B disease 31% had a serum PSA
      value of 4 ng./ml. or less. Multivariate regression analysis of tumor volume as a
      function of PSA, grade and stage demonstrated that log PSA had the strongest
      association with tumor volume. Goodness-of-fit analysis (coefficient of
      determination) revealed that only 40 to 50% of the PSA levels are explained by
      tumor volume. CONCLUSIONS: These data suggest that the window of curability for
      prostate cancer decreases significantly once the tumor grows to a volume greater
      than 1.5 cc, and that grade and tumor volume are more significantly related to
      stage than PSA.

PMID- 7563354
TI  - Percutaneous cryoablation of the prostate: preliminary results after 95
      procedures.
AB  - PURPOSE: We examined the role of percutaneous cryoablation of the prostate in the
      treatment of prostate cancer. MATERIALS AND METHODS: We performed 95 percutaneous
      cryoablations of the prostate on 87 patients with prostate cancer. Of the
      patients 6 had positive lymph nodes preoperatively, radiation failed in 9 and 9
      began postoperative hormonal therapy because of treatment failure. Mean patient
      age, prostate specific antigen (PSA) level (ng./ml.) and Gleason score were 65.4,
      12.60 and 6.03, respectively. Median followup was 12 months (mean 9.3, range 1 to
      24). In 49 of the 87 patients (56%) the lymph nodes were evaluated before
      cryoablation based on the treatment protocol. RESULTS: Median PSA level at 12
      months was 0.55 ng./ml. (mean 1.73) with a 17% positive biopsy rate at 3 months.
      When the positive lymph node, radiation failure and postoperative hormonal
      therapy groups were removed from analysis, the median PSA level was 0.80 ng./ml.
      (mean 1.86) with a 5% positive biopsy rate. Of the patients in the radiation
      failure group 37% had a positive biopsy at 3 months. Cases were classified
      according to stage, grade and PSA level, and the biopsy results were presented.
      The complications of percutaneous cryoablation of the prostate were reviewed.
      CONCLUSIONS: The low percentage of positive biopsies is encouraging but the
      significance of the persistent PSA levels remains uncertain.

PMID- 7563355
TI  - Prognostic significance of positive surgical margins in radical prostatectomy
      specimens.
AB  - PURPOSE: The prognostic significance of positive surgical margins in radical
      prostatectomy specimens was assessed. MATERIALS AND METHODS: The interval to
      progression (increasing prostate specific antigen level) was measured in 478
      patients by status of the surgical margins. RESULTS: At 5 years, the
      nonprogression rate was 64% for patients with and 83% for those without positive
      surgical margins. With a high grade cancer, seminal vesicle invasion or lymph
      node metastases, positive surgical margins had no effect on prognosis; with
      extracapsular extension and a Gleason score of 6 or less positive surgical
      margins were associated with a higher progression rate. CONCLUSIONS: Prognosis
      was adversely affected by positive surgical margins only in moderately
      differentiated cancers with extracapsular extension alone. If the cancer is
      otherwise confined, positive surgical margins are associated with an excellent
      prognosis unlikely to be improved by adjuvant therapy.

PMID- 7563356
TI  - Clinical and urodynamic effects of intravesical capsaicin treatment in patients
      with chronic traumatic spinal detrusor hyperreflexia.
AB  - PURPOSE: We administered capsaicin, a neurotoxic substance causing a reversible
      suppression of C fiber afferent neuronal activity, in an attempt to decrease
      bladder hyperreflexia. MATERIALS AND METHODS: Capsaicin solution (2 mM.)
      dissolved in 30% alcohol was instilled into the bladders of 10 men with traumatic
      chronic spinal lesions and left in place for 30 minutes. Effects on bladder
      function, including response to cold stimulation, were recorded during treatment,
      immediately after instillation and at followup. RESULTS: Bladder function
      improved in all but 1 patient, which was expressed as an increase in cystometric
      capacity and/or a decrease in maximal detrusor pressure. The effects lasted for 2
      to 7 months. Immediately after capsaicin administration the ice water test was
      negative in half of the patients. CONCLUSIONS: The positive effects on bladder
      function of capsaicin treatment can be explained by the blocking of C fiber
      afferents. The optimum dose and treatment interval are presently not established.
      The ice water test might possibly be used as an instrument to monitor the ideal
      dosage.

PMID- 7563357
TI  - Electrically stimulated gracilis sphincter (dynamic graciloplasty) for treatment
      of intrinsic sphincter deficiency: a pilot study on feasibility and side effects.
AB  - PURPOSE: The feasibility and side effects of electrically stimulated gracilis
      sphincter (dynamic graciloplasty) were studied in 7 patients with severe
      incontinence due to intrinsic sphincter deficiency. MATERIALS AND METHODS: The
      distal part of the gracilis muscle is wrapped around the bladder neck.
      Afterwards, 2 muscle electrodes and a programmable pulse stimulator are
      implanted. During a stimulation program the fatigable type 2 skeletal fibers are
      replaced by slow type 1 fibers, which are able to sustain a long lasting
      contraction. RESULTS: Among the patients 3 are continent, 1 is partially
      continent and treatment failed in 3. CONCLUSIONS: The results are encouraging.
      Dynamic graciloplasty may have a role in the treatment of intrinsic sphincter
      deficiency.

PMID- 7563359
TI  - Modified Pereyra bladder neck suspension: 10-year mean followup using outcomes
      analysis in 125 patients.
AB  - PURPOSE: We attempt to determine the long-term success rate of the modified
      Pereyra bladder neck suspension, identify preoperative factors predictive of long
      term outcome, and investigate the influence of method and length of followup on
      reported continence status after modified Pereyra bladder neck suspension.
      MATERIALS AND METHODS: The charts of 177 patients who underwent modified Pereyra
      bladder neck suspension at our institution more than 5 years ago were reviewed.
      An attempt was made to contact all patients either by mail or telephone to
      complete a patient survey questionnaire. RESULTS: Of 177 patients 125 (71%)
      completed the patient survey with a mean followup of 9.8 years. At survey
      followup 20% of the patients reported no incontinence of any type and 51%
      reported stress urinary incontinence with or without urge incontinence. Of the
      patients 71% reported significant improvement in the incontinence and 73% were
      satisfied with the results of the procedure. No accurate preoperative predictors
      of long-term outcome were identified. The method and length of followup had
      significant impact on reported continence status after modified Pereyra bladder
      neck suspension. CONCLUSIONS: This long-term study using outcomes analysis
      reveals a high rate of recurrent stress incontinence after modified Pereyra
      bladder neck suspension. However, most patients maintain significant subjective
      improvement and remain satisfied with the results of the operation.

PMID- 7563358
TI  - Continuous occlusion test to determine detrusor contractile performance.
AB  - PURPOSE: A study was conducted to determine the merits of the continuous
      occlusion test as a method of detrusor contractility assessment by comparing it
      with other stop tests and with contractility derived from pressure-flow analysis.
      MATERIALS AND METHODS: The continuous occlusion test was performed in elderly men
      by occluding the bladder outlet before the onset of a detrusor contraction and it
      was repeated to assess reproducibility. The magnitude of the isovolumetric
      contraction, maximum slope of the detrusor contraction, and duration of detrusor
      activation were determined. Voluntary and mechanical stop tests were performed
      during the mid voiding phase. Continuous occlusion test parameters were compared
      with the pressure-flow contractility parameters. RESULTS: The continuous
      occlusion test was evaluated in 159 patients. The maximum isovolumetric
      contraction pressure of the continuous occlusion test was significantly higher
      than that of the voluntary stop test (49 patients). Continuous occlusion test
      contractility parameters were reproducible. The maximum isovolumetric contraction
      pressure and the maximum slope of the detrusor contraction of the continuous
      occlusion test significantly correlated with the estimated maximum isovolumetric
      contraction pressure and estimated velocity of shortening (derived from pressure
      flow), respectively (r = 0.79, p < 0.0001 and r = 0.385, p = 0.016, 39 patients).
      The watts factor was well correlated with maximum isovolumetric contraction
      pressure (r = 0.75, 39 patients). CONCLUSIONS: Our study suggests that the
      continuous occlusion test can be used as an effective alternative method of
      assessing detrusor contractility.

PMID- 7563360
TI  - Lower urinary tract dysfunction.

PMID- 7563361
TI  - Urodynamic study of storage and evacuation of urine in patients with a urethral
      Kock pouch.
AB  - PURPOSE: The urodynamics of pouch-urethra function were investigated in patients
      with a urethral Kock pouch to understand mechanisms involved in the storage and
      evacuation of urine, and elucidate any problems of long-term outcome. MATERIALS
      AND METHODS: Urodynamic evaluation was performed in 18 male patients who
      underwent bladder replacement with a urethral Kock pouch following radical
      cystectomy. RESULTS: Good urinary continence was achieved with normal frequency
      of voiding. On urodynamics pressure within the pouch remained low during the
      storage phase (mean 33.2 cm. water) but markedly increased during the evacuation
      of urine (mean 77.3 cm. water). In 8 patients (44%) extremely high pressure
      within the pouch (80 to 150 cm. water) was noted at voiding. Clean intermittent
      self-catheterization was initiated in a patient with high pressure within the
      pouch at voiding in whom pouch-ureter reflux developed 7 months postoperatively.
      The external urethral sphincter was impaired to some extent postoperatively but
      it contracted in response to filling of the pouch with a marked increase in
      urethral pressure from a mean of 31.6 to 66.3 cm. water. CONCLUSIONS: Urodynamic
      and radiological studies will be necessary periodically since high pressure
      within the pouch at voiding might jeopardize the antireflux mechanism, leading to
      reflux and renal impairment.

PMID- 7563363
TI  - Primary transitional cell carcinoma arising at the site of previous dismembered
      pyeloplasty.

PMID- 7563364
TI  - Knotting of a double pigtail stent within the ureter: an initial report.

PMID- 7563362
TI  - Spontaneous regression of pulmonary metastasis from nonfunctioning adrenocortical
      carcinoma after removal of the primary lesion: a case report.

PMID- 7563365
TI  - Vesicovaginal fistula after laser vaporization of vaginal condyloma.

PMID- 7563367
TI  - Refractory epididymitis and ejaculatory duct obstruction.

PMID- 7563366
TI  - Arteriovesical fistula after pancreatic transplantation.

PMID- 7563368
TI  - Primary malignant melanoma of the prostate.

PMID- 7563369
TI  - Urology peer review at the National Institutes of Health.
AB  - PURPOSE: Urology is a field with many subspecialties and, as a consequence,
      urological research grant applications are distributed to a variety of different
      study sections at the National Institutes of Health (NIH). It has long been the
      conviction of urological investigators that urological grant funding suffers as a
      result of this distribution. We investigated the composition of these study
      sections to identify the prevalence of urological expertise (or lack thereof).
      The review challenges the concept that urological research grant applications are
      being subjected to adequate peer review. MATERIALS AND METHODS: Aided by
      personnel from the National Institute for Diabetes, and Digestive and Kidney
      Diseases, and the National Cancer Institute, 22 study sections to which
      urological grants are distributed were identified. A 3 to 5-year retrospective
      MEDLINE analysis of all the scientific publications of each study section member
      was done. Urological experts were identified by the criterion of having more than
      1 urological publication published per year or a proportional equivalent. An
      equivalent analysis was performed for the study sections reviewing cardiology
      grants to serve as a comparison. RESULTS: Data analysis revealed that only 12 of
      351 study section members reviewing urological grants are urological experts
      (3.4%). Only 3.1% of the collective published productivity of these members is in
      the broadly defined field of urological investigation. Omitting the published
      productivity of these 12 experts, less than 1% of the published works of the
      remaining 339 members reflects interest or expertise in urological
      investigations. Of the 22 study sections only 8 have urological expertise
      represented in their membership. Except for 1 study section, representation of
      urological experts was usually limited to 1 individual reflecting a 5.9 to 11.1%
      minority in these study sections. CONCLUSIONS: The lack of urological expertise
      represented on the NIH study sections reviewing basic and clinical urological
      research grant applications has far reaching ramifications. Consequently, grant
      applications on genitourinary diseases that commonly afflict a preponderance of
      Americans are inadequately reviewed at the NIH. Only through the provision of
      appropriate peer reviewers will this problem be solved.

PMID- 7563370
TI  - Re: Fluconazole treatment in Torulopsis glabrata upper urinary tract infection
      causing ureteral obstruction.

PMID- 7563371
TI  - Re: Functional replacement of bladder and urethra after cystectomy for bladder
      cancer in a female patient.

PMID- 7563372
TI  - Re: The lowest effective dose of prostaglandin E1 as treatment for erectile
      dysfunction.

PMID- 7563373
TI  - Re: Synchronous management of anastomotic contracture and stress urinary
      incontinence following radical prostatectomy.

PMID- 7563374
TI  - Re: Video laparoscopic excision of a seminal vesicle cyst associated with
      ipsilateral renal agenesis.

PMID- 7563375
TI  - Urinary tract obstruction in children.
AB  - PURPOSE: Perinatal identification of children with congenital urinary obstruction
      has challenged our understanding of the pathophysiology and clinical treatment of
      many children with hydronephrosis. MATERIALS AND METHODS: A critical review of
      recent reports relating to congenital urinary obstruction in children was
      performed in an attempt to integrate clinical and experimental information.
      RESULTS: Several themes emerged from the many reports relating to congenital
      urinary obstruction that have not been previously emphasized. Congenital
      obstruction begins and evolves in a developing fetal kidney, indicating the
      importance of the effect of obstruction on renal growth and development, which is
      distinct from the postnatal renal response to obstruction. Variation in the
      ability of the developing kidney to compensate for obstruction may be an
      important factor in explaining variability in clinical and experimental reports.
      Clinical data show an unpredictable outcome of congenital hydronephrosis.
      Nonoperative management of hydronephrosis is supported by empirical evidence yet
      raises many questions regarding the certainty of outcome and the risks involved.
      It imposes on the practitioner a significant clinical obligation. The ability to
      differentiate between clinically significant and insignificant obstruction is the
      current challenge to be fulfilled by integrated clinical and experimental
      investigation. CONCLUSIONS: The unique features of congenital urinary obstruction
      separate it from better understood acquired postnatal obstruction. Understanding
      the effects of obstruction on the developing kidney prenatally and postnatally is
      critical. A definition is proposed for congenital urinary obstruction in
      children, that is a condition of impaired urinary drainage which, if uncorrected,
      will limit the ultimate functional potential of a developing kidney.

PMID- 7563376
TI  - Diuretic enhanced duplex Doppler sonography in 33 children presenting with
      hydronephrosis: a study of test sensitivity, specificity and precision.
AB  - PURPOSE: We assessed the value of diuretic enhanced Doppler sonography in the
      diagnosis of pediatric renal obstruction as well as its reproducibility,
      sensitivity and specificity. MATERIALS AND METHODS: We studied 33 children (68
      kidneys) by standard diagnostic techniques and diuretic Doppler sonography. A
      total of 20 obstructed kidneys was compared to 48 without obstruction and we
      performed surgery on 13. An average of 2.3 resistive index measurements were made
      per test and 436 total resistive index values were assessed by Student's t
      distribution and chi-square analysis before and after surgical repair. The
      assessor was blinded to the clinical diagnosis. RESULTS: The obstructed mean
      resistive index before (0.71) and after (0.74) furosemide administration differed
      significantly from the nonobstructed mean resistive index (0.65, p < 0.02).
      Postoperative mean resistive index (0.68) was not affected by the diuretic and
      did not differ from the mean resistive index of nonobstructed kidneys. Resistive
      index test sensitivity was 76% and specificity was 88%. The precision for 3
      values per test was +/- 0.11. CONCLUSIONS: When at least 3 values are obtained
      per test, diuretic Doppler sonography predicts the actual resistive index average
      with 98% confidence limits 90% of the time.

PMID- 7563377
TI  - Outcome analysis of pediatric pyeloplasty as a function of patient age,
      presentation and differential renal function.
AB  - PURPOSE: We retrospectively reviewed a consecutive series of patients who
      underwent pyeloplasty. In all cases preoperative and postoperative isotope renal
      scans were performed to assess the surgical outcome with particular emphasis on
      the change in renal function postoperatively. MATERIALS AND METHODS: The clinical
      records of 108 consecutive children with ureteropelvic junction obstruction were
      reviewed. Individual renal function was evaluated and obstruction was confirmed
      by diuretic assisted 99mtechnetium diethylenetriaminepentaacetic acid or
      mercaptoacetyltriglycine renography. A total of 100 pyeloplasties in 98 children
      between 5 days and 16 years old was included. Results were analyzed by groups
      according to patient age and symptoms at presentation. RESULTS: Drainage half
      times improved in 98% of patients and only 1 required reoperation. Improved renal
      function greater than 5% was noted in about a third of each age group. Function
      remained stable in 68% of the kidneys and decreased in only 1. Of the improved
      kidneys 77% had impaired function preoperatively (40% or less of the total
      contribution). Those presenting with a renal mass had the greatest improvement in
      function. There was no statistically significant difference in improvement in
      renal function by age group or patient presentation. Regression analysis revealed
      that preoperative differential renal function was the only statistically
      significant predictor of improvement in renal function after pyeloplasty.
      CONCLUSIONS: Pyeloplasty in children is safe and renal functional improvement can
      be expected in the majority of kidneys with impaired function at presentation.
      However, there was no indication that early pyeloplasty in infants is more likely
      to result in improved function than in older children.

PMID- 7563378
TI  - Retroperitoneal foreign body presenting as a sarcomatous bladder tumor.

PMID- 7563379
TI  - Relative microbial resistance of gastric, ileal and cecal bladder augmentation in
      the rat.
AB  - PURPOSE: Bladder resistance to bacterial infection after gastrocystoplasty,
      ileocystoplasty and cecocystoplasty was investigated in the rat. MATERIALS AND
      METHODS: Bladders were infected with Escherichia coli 6 to 13 months after
      augmentation and urine culture was obtained weekly for 3 months. RESULTS: No
      differences were observed in the number of infected animals within each group or
      electrolyte data among groups. The number of animals infected after surgery but
      before E. coli challenge was lowest in the gastrocystoplasty group. Bladder
      stones formed only in ileocystoplasty and cecocystoplasty groups. No group had a
      change in urinary pH. CONCLUSIONS: Gastrocystoplasty may be associated with a
      lower incidence of spontaneous infection and stone formation. An aggressive
      infection protocol may have masked differences in susceptibility to infection.
      Since urinary pH was unchanged after gastrocystoplasty, use of the rat may not be
      appropriate for augmentation studies.

PMID- 7563380
TI  - Prevalence and repair of inguinal hernias in children with bladder exstrophy.
AB  - PURPOSE: We delineated the prevalence, recurrence rates and optimal treatment of
      inguinal hernia in the exstrophy population. MATERIALS AND METHODS: Of 181
      children with exstrophy followed at our hospital inguinal hernias developed in
      121 (66.8%). RESULTS: In a 12-year period inguinal hernias developed in 81.8% of
      the boys and 10.5% of the girls. In 18.2% of the cases the hernia was repaired
      via a preperitoneal approach at the same time as exstrophy closure. The remaining
      patients underwent an inguinal operation. Most patients had a wide defect at the
      internal ring in addition to a patent processus vaginalis. The overall recurrence
      rate was 8.3%. The incidence of synchronous or asynchronous bilaterality was
      81.8%. CONCLUSIONS: Children with bladder exstrophy should be carefully examined
      for inguinal hernias before bladder closure. If a unilateral hernia is present,
      the contralateral side should be explored. Careful preperitoneal repair should
      emphasize repair of the internal ring.

PMID- 7563381
TI  - Psychosexual adjustment of children and adolescents after different types of
      hypospadias surgery: a norm-related study.
AB  - PURPOSE: We studied the psychosexual adjustment, sexual behavior and genital
      appraisal of 9 to 18-year-old hypospadias patients. MATERIALS AND METHODS: We
      interviewed 116 hypospadias patients and 88 comparison subjects in a semi
      structured manner. RESULTS: Hypospadias patients had a more negative genital
      appraisal and anticipated more ridicule by a partner because of penile appearance
      than comparison subjects but they did not have a different sexual adjustment. No
      significant impact of medical treatment (surgical procedures, number of
      operations or age at final surgery) was noted. Many hypospadias patients (38.8%)
      desired functional or cosmetic penile improvement. CONCLUSIONS: In addition to
      procedures that bring the meatus to a more terminal position, those that bring it
      more ventral can be performed without negatively affecting psychosexual
      adjustment. Hypospadias patients were reluctant to seek advice for problems and,
      therefore, they should be followed through adolescence.

PMID- 7563382
TI  - Accessory scrotum located on the distal penile shaft.

PMID- 7563383
TI  - Effect of the potassium channel opener YM934 on the contractile response to
      electrical field stimulation in pig detrusor smooth muscle.
AB  - PURPOSE: The effect of a potassium channel opener, YM934, on the contractile
      response to excitatory neurotransmitters was investigated in isolated pig
      detrusor smooth muscle. MATERIALS AND METHODS: Electrical field stimulation (EFS;
      5 second trains, 50 V, 0.8 msec. duration), alpha, beta-MeATP (3 x 10(-7) to 10(
      5) M.) or carbachol (3 x 10(-8) to 10(-6) M.) produced a contractile response in
      isolated pig detrusor smooth muscle. The effect of YM934 on the contractile
      responses was evaluated in comparison with the antagonism of the putative
      cotransmitters, acetylcholine and ATP. RESULTS: A tetrodotoxin-sensitive,
      frequency-dependent contractile response to electrical field stimulation was
      obtained. Atropine (3 x 10(-8) M.) significantly inhibited the contractile
      response at high frequencies, whereas alpha, beta-MeATP (5 x 10(-6) M.)
      (desensitizer of P2X-purinoceptors) significantly inhibited the response at low
      frequencies. YM934 (10(-8) to 10(-7) M.) dose-dependently inhibited the nerve
      mediated contractile responses to all frequencies but preferentially at low
      frequencies, by analogy with alpha, beta-MeATP. A combination of YM934 (3 x 10(
      8) M.) and atropine (3 x 10(-8) M.) reduced the response at all frequencies to
      between 10 and 20% of control, an effect similar to that obtained with alpha,
      beta-MeATP (5 x 10(-6) M.) and atropine (3 x 10(-8) M.). In addition, YM934 (3 x
      10(-8) M.) markedly inhibited the contractile response induced by exogenously
      applied alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) but only slightly inhibited
      the contractile response induced by exogenously applied carbachol (3 x 10(-8) to
      10(-6) M.). CONCLUSION: These results suggest that YM934 may hyperpolarize the
      membrane of pig detrusor smooth muscle through the opening of ATP-sensitive
      potassium channels and, as a result, may functionally inhibit the contractile
      response to purinergic nerve stimulation that elicits the membrane
      depolarization.

PMID- 7563384
TI  - Effect of pH on myofilament Ca(2+)-sensitivity in alpha-toxin permeabilized
      guinea pig detrusor muscle.
AB  - PURPOSE: To ascertain if the inotropic effects of altered intracellular pH on
      detrusor smooth muscle could be explained by a change in Ca(2+)-sensitivity of
      the contractile proteins. MATERIALS AND METHODS: Guinea pig detrusor smooth
      muscle was permeabilized with alpha-toxin and exposed to solutions mimicking the
      composition of the intracellular compartment and of varying [Ca2+]. Isometric
      tension was measured during exposure to solutions of varying [Ca2+] at pH 6.3,
      7.1 and 7.5. RESULTS: At pH 7.1 the pCa (-log10[Ca2+]) required for half-maximal
      activation (pCa50) was 6.00 +/- 0.07 at 22C. A Hill coefficient of unity
      suggested lack of cooperativity in myofilament Ca2+ activation. A decrease of pH
      from 7.1 to 6.3 had no significant effect on the pCa50 value or the maximum Ca2+
      activated force. An increase to pH 7.5 decreased the pCa50 value by 0.65 +/- 0.20
      units but left maximum force unaffected. CONCLUSIONS: The reduced Ca2+
      sensitivity of detrusor myofilaments at alkaline pH could partly explain the
      negative inotropic effect of intracellular alkalosis in intact muscle. The
      positive inotropic effect of intracellular acidosis cannot, however, be explained
      by alteration to myofilament Ca2+ sensitivity.

PMID- 7563385
TI  - A model of bladder tumor xenografts in the nude rat.
AB  - PURPOSE: An in vivo tumor model for the study of human urothelial carcinoma is
      desirable. Orthotopic xenografts are useful in order to better approximate human
      tumor cell behavior in situ. A prior model has been described in the nude mouse.
      However, its small bladder size limits both histologic characterization and the
      application of intravesical therapeutics. In the absence of preirradiation,
      orthotopic xenografts of human transitional cell carcinoma in the nude rat has
      not been previously reported. MATERIALS AND METHODS: Nude rats 2 to 4 weeks of
      age were inoculated with 1-5 x 10(6) cells of RT4 (well differentiated papillary
      human bladder tumor cell line). Inoculation was performed via open cystotomy.
      Techniques of mucosal injury including acid treatment and cautery were explored
      in an effort to optimize tumor implantation and growth. Animals were sacrificed
      at varying intervals and histologic assessment was performed. RESULTS: The
      overall rate of tumor implantation and growth was 93.4% (57 of 61). Tumors
      reliably grew within the muscularis and mucosal growth was seen as well.
      Intramuscular tumor growth was less differentiated and had a higher fraction of
      mitotic cells than mucosal tumor. Tumor growth was consistently seen as early as
      2 weeks after inoculation which facilitates experimental trials. Distant
      metastasis was not observed. Mucosal injury did not increase the rate of tumor
      implantation. CONCLUSION: This model is highly reproducible and will prove useful
      in the further study of bladder cancer progression as well as in the development
      of therapeutic modalities for both superficial and muscle invasive bladder
      carcinoma.

PMID- 7563386
TI  - Effect of orchiectomy on the alpha adrenergic contractile response of dog
      prostate.
AB  - PURPOSE: To investigate the effect of androgen deprivation on the alpha
      adrenergic contractile response of the dog prostate using both in vitro and in
      vivo methods. MATERIALS AND METHODS: In vitro muscle bath study: One month after
      surgery, responses to KCl (120 mM.) and norepinephrine (10(-8) to 10(-3)M.) of
      prostatic tissue strips (of the same size) from castrated (n = 6) and sham
      operated (n = 6) adult mongrel dogs were determined. In vivo study: Before and 1
      month after surgery, the intraprostatic urethral pressure response to intravenous
      norepinephrine administration of 6 castrated and 5 sham-operated adult dogs was
      examined. RESULTS: (1) Before castration the serum level of testosterone was 1.24
      +/- 0.2 ng./ml.; 1 month after castration, it had dropped to an undetectable
      level. (2) Histological examination of the prostates from castrated animals
      revealed profound atrophy of glandular tissue with a relatively increased stromal
      tissue component in each section. (3) In vitro study: The contractile responses
      to KCl and norepinephrine of individual prostate strips (same size) from
      castrated animals were significantly higher than control. However, if the
      response to norepinephrine was normalized to the response to KCl, there was no
      significant difference in response to norepinephrine between the 2 groups. In
      addition, the ED50 of the norepinephrine-stimulated contractile response was not
      changed by castration. (4) In vivo study: There was no significant change in
      intraprostatic urethral pressure response to intravenous norepinephrine
      administration after orchiectomy. CONCLUSIONS: The results of this study show
      that the sensitivity of the alpha-adrenergic contractile response of the dog
      prostate is not affected by androgen deprivation, nor is alpha-adrenergic
      contractile activity of the dog prostate regulated by androgen.

PMID- 7563387
TI  - Laparoscopic assisted continent urinary diversion in the pig.
AB  - PURPOSE: The ideal urinary reservoir would be low pressure, nonrefluxing and
      simple to construct. Hohenfellner recently described creating an in situ
      ureterosigmoidostomy with a 5 to 6 cm. detubularized portion of sigmoid colon and
      rectum (sigmoid-rectum pouch). In an effort to further study the reconstructive
      applications of laparoscopy, we sought to laparoscopically create a sigmoid
      rectum pouch in an animal model. In addition, we sought to compare a "dunked"
      (right ureter) with a hand-sewn end-to-side ureterocolonic anastomosis (left
      ureter). MATERIALS AND METHODS: Nine male domestic pigs underwent laparoscopic
      creation of a continent urinary diversion. Pouch creation and the ureterocolonic
      anastomoses were done extracorporeally; ureteral stents were not used. Average
      operative time was 122 minutes. Eight pigs survived the 10 to 12 week study
      period. RESULTS: Mean pouch capacity was 360 cc and pouch pressure remained < 20
      cm.H2O. Stones were noted on the bowel staple line in 44% of the animals.
      Ureterocolonic obstruction occurred in 11% of the right ureters and 33% of the
      left ureters. CONCLUSIONS: A laparoscopically created continent sigmoid-rectum
      diversion appears to be feasible. A "dunked" ureterocolonic anastomosis provides
      equivalent or better drainage than a traditional hand-sewn ureterocolonic
      anastomosis. Problems with stone formation on the titanium staple line need to be
      resolved.

PMID- 7563389
TI  - The effect of iontophoresis on bacterial growth in urine.
AB  - PURPOSE: To determine the effect of iontophoresis (electrical current for
      therapeutic purposes) on the growth of pathogenic bacteria in human urine.
      MATERIALS AND METHODS: Pathogenic bacteria were isolated and inoculated into a
      dynamic in vitro artificial bladder model. Pooled sterile human urine was
      regulated through the artificial bladder by intravenous tubing and pumps to
      simulate filling and emptying of the human bladder. The effect of electrical
      current on bacterial growth in the system was then studied. RESULTS: When
      iontophoresis is applied at low bacterial concentrations ( < 10(8) colony forming
      units [CFU]/l.), inhibition of bacterial growth occurs. However, when
      iontophoresis is applied after fulminant growth of bacteria ( > 10(8) CFU/l.), no
      inhibition of bacterial growth occurs. Iontophoresis was not found to enhance the
      antibacterial action of gentamicin to resistant Pseudomonas aeruginosa.
      CONCLUSIONS: Iontophoresis inhibits bacterial growth at low bacterial
      concentrations. It does not inhibit bacterial growth after infectious levels have
      been attained, and it does not potentiate the action of gentamicin on resistant
      Pseudomonas aeruginosa.

PMID- 7563388
TI  - The effect of extracorporeal electromagnetic shock waves on the morphology and
      contractility of rabbit ureter.
AB  - PURPOSE: Although extracorporeal shock wave lithotripsy (ESWL) is known to cause
      pathologic changes in various organs, little is known about its effects on the
      ureter, the target organ in ESWL of ureteral stones in situ. In this study, we
      sought to determine the short-term effects of ESWL on the ureter. MATERIALS AND
      METHODS: Left lower ureteral segments of 21 rabbits were removed to serve as the
      control group and 2000 shocks were applied to the right lower ureters. Groups of
      7 rabbits were sacrificed 1, 3 and 5 days after shock wave exposure. While
      histomorphological alterations were examined under light and transmission
      electron microscopy, contractility of all ureters was determined in organ baths.
      RESULTS: The epithelial cells disclosed no change after shock wave application.
      Histologically the muscular layer was the most affected part of the ureter. There
      was interstitial and intracellular edema on light microscopy and marked chromatin
      and mitochondrial changes at the subcellular level. The adventitial layer was
      also edematous. These changes were prominent on days 1 and 3 and returned to
      normal on day 5. The contractility of the ureters on day 1 was significantly
      reduced (p < 0.05). However, the contractility of the samples on days 3 and 5
      were not significantly different from controls. CONCLUSION: Our findings
      demonstrate that electromagnetic shock waves produce reversible morphological and
      functional changes in rabbit ureteric muscle.

PMID- 7563390
TI  - In vivo reduction of bacterial populations in the urinary tract of catheterized
      sheep by iontophoresis.
AB  - PURPOSE: Iontophoresis kills microbes in vitro and, therefore, may be a useful
      method for eliminating microbial populations associated with catheter-induced
      urinary tract infections in vivo. MATERIALS AND METHODS: Catheters were modified
      to deliver current to platinum electrodes in the catheter tip. Female sheep were
      catheterized with this iontophoretic catheter and left ambulatory. In 5 sheep
      (experimental group) 400 microA was applied to the catheter and withheld in 4
      sheep (control group) for 20 to 21 days. The animals were then sacrificed. During
      the study, types and concentrations of bacteria, and physical and chemical
      characteristics of the urine samples were determined. RESULTS: Throughout the
      study, bacteria levels were reduced in urinary tracts of the experimental group
      (10(3) to 10(4) microbes per ml.) compared with the control group (10(7) microbes
      per ml.), without extensive alterations to urine chemistry or the sheep urinary
      tract. CONCLUSIONS: Since iontophoresis safely reduced bacterial populations in
      catheterized sheep, this technology may reduce or eliminate nosocomial, catheter
      induced urinary tract infections in humans.

PMID- 7563391
TI  - Alterations of the p16 (MTS1) gene in testicular, ovarian, and endometrial
      malignancies.
AB  - PURPOSE: The p16 (MTS1) gene codes for a cyclin-dependent kinase inhibitor and
      may be a new tumor suppressor gene. It is frequently mutated in a variety of cell
      lines established from tumors. This is the first report of screening for
      alteration of the p16 gene in testicular, ovarian and endometrial malignancies.
      MATERIALS AND METHODS: We examined alterations of p16 in 78 primary genital
      tumors (42 testicular, 21 ovarian and 15 endometrial cancers) and mononuclear
      cells from 2 patients with Lynch syndrome II as well as 5 testicular tumor cell
      lines by single-strand conformation polymorphism (SSCP) and Southern blot
      hybridization. RESULTS: The DNA from the p16 gene of 2 testicular tumors (5%), an
      ovarian cancer (4%) and a testicular tumor cell line (20%) had altered migration
      in gel electrophoresis as shown by SSCP. Analysis of DNA sequence of these
      samples revealed a polymorphism at codon 140. Southern blot hybridization
      detected neither deletions nor rearrangements of the p16 gene in any of the
      samples. CONCLUSIONS: Taken together, these results suggest that p16 alterations
      probably are not important for tumorigenesis of testicular, ovarian and
      endometrial tumors.

PMID- 7563392
TI  - Stage specific identification of the expression of GnRH mRNA and localization of
      the GnRH receptor in mature rat and adult human testis.
AB  - PURPOSE: To identify the expression of gonadotropin-releasing hormone (GnRH)
      messenger ribonuclueic acid (mRNA) and localize GnRH receptors in mature rat and
      adult human testes. MATERIALS AND METHODS: In situ hybridization and enzymatic
      receptor binding localization were performed. RESULTS: GnRH mRNA was expressed
      within the seminiferous tubules in both mature rat and adult human testis. In
      rats, expression of GnRH mRNA was identified in the Sertoli cells and
      spermatogenic cells of some seminiferous tubules, but the other tubules did not
      express any hybridization signal. In humans, expression of GnRH mRNA was
      identified only in some spermatogenic cells in some seminiferous tubules. The
      receptors for GnRH were localized to cells in the interstitial tissues of the
      testis, probably Leydig cells. CONCLUSION: The authors believe that the mature
      rat and adult human seminiferous tubular cells produce GnRH at the same specific
      stage of the spermatogenic cycle and that GnRH produced within seminiferous
      tubules, including Sertoli cells and spermatogenic cells, reacts with neighboring
      GnRH receptors in interstitial cells, including Leydig cells. The GnRH produced
      from the Sertoli cells in seminiferous tubules would react with GnRH receptors in
      interstitial cells as a paracrine hormone.

PMID- 7563393
TI  - Prognostic value of p53 nuclear overexpression in patients with invasive bladder
      cancer treated with neoadjuvant MVAC.

PMID- 7563394
TI  - Does neoadjuvant cisplatin-based chemotherapy improve the survival of patients
      with locally advanced bladder cancer: a meta-analysis of individual patient data
      from randomized clinical trials. Advanced bladder cancer overview collaboration.

PMID- 7563395
TI  - A pharmacogically guided phase I study of carboplatin in combination with
      methotrexate and vinblastine in advanced urothelial cancer.

PMID- 7563396
TI  - Redistribution of blood flow after carotid endarterectomy.
AB  - PURPOSE: We wanted to characterize the immediate effect of endarterectomy on flow
      of the arteries composing the extracranial carotid artery system. METHODS:
      Transit time ultrasound probes were used to measure flow through the carotid
      bifurcation in 48 patients undergoing endarterectomy. Maximum single-diameter
      stenosis affecting the internal carotid artery (ICA) was determined by
      angiography. The significance of differences between means were determined by t
      tests and analysis of variance; linear and nonparametric correlation analyses
      were also applied to analyze the relation between stenosis and several flow
      derived parameters. RESULTS: Common carotid artery flow significantly increased
      (p = 0.0043) from a mean value of 264 +/- 99 ml/min to 314 +/- 98 ml/min,
      corresponding to an average percent increase of 34.3% +/- 71.3%. ICA flow
      increased from 128 +/- 69 ml/min to 173 +/- 66 ml/min (p < 0.0001), with an
      average percent increase of 74.9% +/- 114.9%. External carotid artery (ECA) flow
      decreased from 129 +/- 61 ml/min to 106 +/- 49 ml/min (p = 0.0098), representing
      an average percent decrease of -5.2% +/- 48.2%. The difference between ECA and
      ICA mean flow changes is highly significant (p < 0.001). The percent change in
      ECA flow did not correlate with preoperative stenosis. We noted, however, a
      positive correlation between stenosis and the ECA/ICA flow ratio before
      endarterectomy (Spearman r = 0.31, p = 0.032), indicating that more severe
      stenosis led to a greater distribution of blood into the ECA. The ECA/ICA flow
      ratio fell from an initial value (ECFbef/ICFbef) of 1.52 +/- 1.74 before
      endarterectomy to 0.69 +/- 0.37 (ECFaft/ICFaft) after endarterectomy (p =
      0.0006). CONCLUSIONS: The data are consistent, with the ECA being an important
      collateral path for cerebral perfusion when ICA stenosis exists. When
      endarterectomy relieves bifurcation stenosis, common carotid artery blood flow is
      redistributed preferentially to the ICA at the expense of ECA flow, consistent
      with a change in the relative resistances of the two vessels resulting from
      operative reconstruction.

PMID- 7563398
TI  - Preliminary experience with the Endovascular Technologies bifurcated endovascular
      aortic prosthesis in a calf model.
AB  - PURPOSE: The purpose of this study was to develop a bifurcated endoluminal
      prosthesis for transfemoral placement in the aortoiliac position with a large
      animal model that would simulate human implantation. METHODS: Fifteen calves (160
      to 200 kg) underwent bilateral femoral artery exposure and transfemoral placement
      in the aortoiliac position of a bifurcated Dacron prosthesis, inserted through a
      26F sheath with an over-the-bifurcation guide wire to retrieve the contralateral
      limb and secured proximally and distally with self-expanding attachment systems.
      The preferred location was determined before implantation and compared with final
      implant location by caliper measurements and angiography. Events during
      implantation, maneuvers used to accomplish accurate deployment, and final
      results, as judged by angiography and clinical evaluation, were recorded. Four
      animals survived and were used for chronic evaluation and healing by gross and
      microscopic studies. RESULTS: All grafts (n = 15) were patent at the end of the
      procedure. All (n = 7) noncrimped grafts had minor kinks in areas of curvature,
      whereas eight of eight crimped grafts (device modification) had none. Torque
      control of the body and individual limbs was necessary to correct twists before
      deployment in 10 of 15 grafts, with two greater than 30-degree twists remaining,
      which did not appear to affect flow. One implant was entirely deployed in the
      aorta because of parallax error, subsequently avoided by use of a marker board
      placed dorsally. Three premature deployments occurred, corrected by attachment
      system lock modification. The mean final implant position was within 2.9 +/- 1.4
      mm (aortic), 1.6 +/- 1.1 mm, and 1.5 +/- 0.8 mm (contralateral and ipsilateral
      iliac limbs, respectively) of the intended position. Three of four animals
      intended for long-term evaluation were killed prematurely because of clinically
      evident spinal cord ischemia. Histologic sections at 2 weeks showed early wall
      repair without inflammatory cells and pannus ingrowth across the anastomosis.
      CONCLUSION: We conclude that implantation of a bifurcated endovascular prosthesis
      through the bilateral femoral approach is possible, provided the intended aortic
      implantation site (neck) is at least 12 mm in length (mean +/- 2 SD each
      direction). Torque control of each portion of the device will be needed in the
      majority of instances, with attention to parallax effect necessary for optimal
      placement. This animal model is not suitable for chronic graft evaluation because
      of its sensitivity for spinal cord ischemia. Healing data suggest graft
      incorporation similar to that of a surgically placed prosthesis.

PMID- 7563399
TI  - Effect of differential shear stress on platelet aggregation, surface thrombosis,
      and endothelialization of bilateral carotid-femoral grafts in the dog.
AB  - PURPOSE: The purpose of this study was to determine the effects of increased
      shear stress on the aggregability of platelets as they traverse a long, small
      caliber (6 mm) Dacron graft in the dog and on the surface thrombosis and
      endothelialization of such a graft. METHODS: Each of nine dogs received bilateral
      carotid-femoral artery grafts, approximately 75 cm long, for 3 months; one graft
      of each pair had a distal femoral arteriovenous fistula to produce a higher shear
      rate than the contralateral graft. Platelet aggregation scores were determined on
      blood withdrawn from the external jugular vein and from the proximal and distal
      ends of the grafts in each animal. Graft flow rates, which were used in the
      computation of shear stress, and luminal pressure gradients through grafts were
      measured during surgery and specimen retrieval. Specimens were studied with light
      microscopy after hematoxylin and eosin and immunocytochemical staining and by
      scanning electron and transmission electron microscopy to evaluate the nature,
      composition, and thickness of the flow surface lining, as well as the transmural
      healing. RESULTS: Two high-shear stress and two low-shear stress grafts occluded
      unilaterally; five dogs had bilaterally patent grafts, allowing comparative
      analyses. All subjects had low platelet aggregability with aspirin. Platelet
      aggregation scores taken from proximal and distal ends of the grafts were not
      significantly different. The high-shear stress grafts had significantly more
      endothelial-like cell coverage (p < 0.0371) than the low-shear stress grafts,
      less flow-surface thrombus (p < 0.0056), and a thinner surface lining (p <
      0.0029), on both the neointima and pseudointima. CONCLUSIONS: In subjects with
      low platelet aggregation scores, long Dacron grafts do not elevate platelet
      aggregability of blood flowing through them. High-shear stress grafts have less
      flow surface thrombus, more endothelialization, and a thinner surface lining than
      do low-shear stress grafts.

PMID- 7563397
TI  - Diagnosis and long-term clinical outcome in patients diagnosed with hand
      ischemia.
AB  - PURPOSE: The long-term clinical outcome of patients diagnosed with digital artery
      obstruction and symptomatic hand ischemia is largely unknown. Our long-term
      experience with the diagnosis of symptomatic digital artery obstruction and the
      long-term natural history of this condition forms the basis for this report.
      METHODS: From 1971 to 1985, 44 patients with symptomatic hand ischemia and palmar
      or digital arterial obstruction underwent arteriography and digital
      photoplethysmography (PPG). Patients were grouped according to severity of hand
      ischemia symptoms, including ulceration and digital amputation and the presence
      of a connective tissue disease (CTD). Arteriography was compared with PPG by
      creating an objective severity scale (digital obstruction index [DOI]). RESULTS:
      Average follow-up was 15.2 years (range 10 to 22 years). Initially 21 patients
      (48%) had moderate symptoms, and 23 patients (52%) had severe symptoms of hand
      ischemia. Follow-up symptoms in 28 patients improved (13 of 26 with CTD, 15 of 18
      without CTD), in 15 patients (12 of 26 with CTD, 3 of 18 without CTD) remained
      unchanged, and in only 1 patient (1 of 26 with CTD) worsened. Seventeen (65%)
      patients with CTD (n = 26) had development of one or more ulcers, and six (24%)
      underwent one or more digital amputations. Four (22%) patients without CTD (n =
      18) had finger ulceration (p < 0.012 compared with patients with CTD), and one
      patient (6%) underwent subsequent digital amputation (p = NS). The arteriography
      DOI and PPG-DOI were equally accurate in determining severity of finger ischemia
      as manifested by severity of symptoms or ulcer development. CONCLUSIONS: The
      favorable long-term prognosis of symptomatic finger artery occlusion described
      herein mandates the avoidance of premature finger amputation. Patients with CTD
      fare worse, but even in this group tissue loss is modest. Finger PPG is as
      accurate as arteriography for determining severity of hand ischemia.

PMID- 7563400
TI  - Durability of cross-femoral grafts after aortic graft infection: the fate of
      autogenous conduits.
AB  - PURPOSE: Revascularization for the treatment of aortic graft infection is usually
      accomplished by remote prosthetic axillofemoral bypass combined with cross
      femoral bypass. When infection at the femoral level precludes placement of a
      prosthetic cross-femoral graft, we have used a variety of autogenous tissue
      conduits to restore circulation to the contralateral leg. To determine which of
      these conduits offers the most durable reconstruction, we have reviewed 78
      patients treated for aortic graft infection. METHODS: Between 1980 and 1991 we
      used either autogenous saphenous vein (ASV, n = 34), endarterectomized
      superficial femoral artery (SFA, n = 14), or direct ilioiliac anastomosis (iliac,
      n = 10) to provide cross-femoral flow. We compared the performance of these
      tissue conduits with a concurrent patient group with aortic graft infection in
      whom a prosthetic cross-femoral graft was used (prosthetic, n = 20). RESULTS:
      Follow-up was available for 98.7% of patients, average 3.8 +/- 2.9 years, and was
      not different between the four groups. Bleeding complications occurred
      exclusively in the ASV group (n = 3, 8.8%) and were all in the perioperative
      period. In addition one ASV and one iliac conduit developed multiple false
      aneurysms. Hemodynamic conduit failure (thrombosis or stenosis) occurred in nine
      (26.5%) ASV conduits, six (42.8%) SFA conduits, and one iliac conduit, but not in
      the prosthetic group. When all of these adverse events were combined for each
      conduit group, both ASV and SFA conduits had a higher rate of conduit failure
      when compared with the prosthetic conduits (p < 0.05, log-rank test). Limb loss
      resulting from cross-femoral conduit failure occurred in six (17.6%) patients in
      the ASV group, four (28.6%) patients in the SFA group, and one patient each in
      the iliac and prosthetic groups. These differences were not significant.
      CONCLUSIONS: We conclude that ASV and SFA conduits do not provide stable long
      term cross-femoral revascularization and should be regarded as bridge grains
      until femoral infection is eradicated. When femoral infection mandates their use,
      frequent postoperative conduit surveillance is required. If ASV or SFA caliber is
      marginal, consideration should be given to the use of a larger autogenous
      conduit, such as superficial femoral vein.

PMID- 7563401
TI  - The incidence of iliac, femoral, and popliteal artery aneurysms in hospitalized
      patients.
AB  - PURPOSE: Previous studies have attempted to determine the incidence and mortality
      rate of abdominal aortic aneurysms in a variety of populations; however, the
      incidence of iliac, femoral, and popliteal artery aneurysms have not been
      established. The objective of this study was to determine the incidence of lower
      extremity aneurysms in hospitalized patients in the state of Utah, which has a
      population at low risk for cardiovascular disease, atherosclerosis, and smoking,
      and to compare the results with the incidence in the United States. METHODS:
      Incidences of iliac, femoral, and popliteal artery aneurysm in Utah were
      determined over a 6-year period, with data obtained via diagnostic codes from the
      Utah Hospital Association. The incidence of iliac, femoral, and popliteal artery
      aneurysms in the United States hospital population was calculated by use of
      National Hospital Discharge Summary 1990 data, a complex sample of nonfederal
      short-stay hospitals in the United States, which provides the most comprehensive
      database of health statistics in the United States. RESULTS: The incidence of
      iliac femoral/popliteal artery aneurysms in hospitalized Utah men is 3.76 and
      4.85 per 100,000 population, respectively. In American men, iliac and
      femoral/popliteal artery aneurysm incidences are 6.58 and 7.39 per 100,000
      population, respectively. Incidences among hospitalized women in Utah are 0.24
      and 1.07 per 100,000; incidences in women in the United States are 0.26 and 1.00
      per 100,000, respectively. The incidence of nonaortic peripheral aneurysms among
      hospitalized patients in Utah is lower than in the United States. The rate ratios
      (Utah/United States) for incidences of iliac, femoral, and popliteal artery
      aneurysms in men are 0.57 and 0.66, respectively (p < 0.05). No statistical
      difference is seen between incidences in women in Utah and the United States (p >
      0.05)-ratios of 0.93 and 1.06, respectively. CONCLUSION: This study validates the
      traditional belief that iliac, femoral, and popliteal artery aneurysms are much
      less frequent, at least in hospitalized patients, than previously published
      incidences of abdominal aortic aneurysms.

PMID- 7563402
TI  - Screening for abdominal aortic aneurysms during lower extremity arterial
      evaluation in the vascular laboratory.
AB  - PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of
      screening for abdominal aortic aneurysms (AAA) during noninvasive lower extremity
      arterial examination in the vascular laboratory. METHODS: Over 30 months we
      screened 531 patients who underwent lower extremity arterial evaluations in the
      vascular laboratory. The patients had fasted overnight, and, after the regular
      noninvasive lower extremity arterial examination, the abdominal aorta was
      screened with B-mode ultrasonography. RESULTS: The aorta was adequately
      visualized in 475 patients (89%). Mean aortic diameter was 19.6 +/- 4.1 mm at the
      juxtarenal level and 18.8 +/- 7.2 mm in the lower infrarenal aorta. The aortic
      diameter was larger in men (p < 0.001) and in smokers (p < 0.001). AAA (diameter
      greater than 3.0 cm) were identified in 32 patients (6.0% of the 531 patients
      screened), and 15 of the aneurysms were equal to or larger than 4.0 cm. The best
      predictors for AAA by logistic regression analysis were male sex (p < 0.005),
      advanced age (greater than 65 years, p < 0.01), and a history of smoking (p <
      0.01). The prevalence of AAA was 6.7% (32/475) in the population in whom the
      aorta was visualized and 15.2% (19/125) in male smokers over 65 years of age.
      Aneurysms of 4.0 cm or greater were identified in 3.2% of the entire population
      screened and 8.8% of male smokers over age 65. Limited aortic scanning prolonged
      the vascular laboratory examination by an average of 5 minutes. Thus detection of
      one aneurysm required 83 minutes of scanning time for the whole population
      studied and 36 minutes of scanning of male smokers over age 65, at a cost of $240
      to $553 per aneurysm identified. CONCLUSION: Screening for AAA during lower
      extremity arterial evaluation in the vascular laboratory addresses a high-risk
      population, is cost-effective, and should be considered an appropriate and
      valuable addition to the examination protocol.

PMID- 7563403
TI  - Ultrasound-guided compression of iatrogenic femoral pseudoaneurysm failure,
      recurrence, and long-term results.
AB  - PURPOSE: Iatrogenic femoral pseudoaneurysms (IFP) have traditionally been treated
      surgically. Recently, this common problem has been successfully treated without
      operation by use of ultrasound-guided compression (UGC) to induce thrombosis of
      the false aneurysm cavity, but the risk factors for failure and the long-term
      outcome have not been defined. METHODS: All patients referred to the vascular
      laboratory from June 1992 to November 1994 whose femoral pseudoaneurysms were
      treated by UGC were included in the study. Data were collected prospectively
      during the last 18 months of the study. Data regarding the location and
      morphologic characteristics of the pseudoaneurysms and anticoagulation status
      were documented. Patients who had successful UGC underwent follow-up duplex
      scanning and ankle-brachial arterial pressure evaluations. RESULTS: Fifty-seven
      patients with IFP were treated with UGC over a 30-month period; the last 34 were
      evaluated prospectively. UGC was successful at obliterating the false aneurysm
      cavity with the initial attempt in 47 (83%). Thrombosis of seven additional
      pseudoaneurysms was achieved on subsequent UGC attempts for an overall success
      rate of 95%. Recurrent false aneurysms were noted in two patients 2 and 10 days
      after initially successful UGC. Both were treated successfully with repeat UGC.
      Multivariate analysis of 14 variables revealed heparin anticoagulation (chi
      square 9.025, p = 0.001) as the only significant risk factor for failure of UGC.
      There were no episodes of arterial thrombosis, embolization, or femoral nerve
      injury associated with UGC. Temporary occlusion of femoral artery during UGC and
      compression intervals of 20 minutes were well tolerated. Long-term follow-up from
      30 to 400 days after UGC was available in 36 patients. There was no late
      recurrence or significant change in ankle-brachial pressures (p > 0.05).
      CONCLUSION: UGC is a safe and effective treatment for most catheter-induced
      femoral pseudoaneurysms with a low complication rate and excellent long-term
      results at a cost substantially lower than operative treatment. Because the
      natural history of IFP is unpredictable, UGC appears to be the preferred
      treatment for all IFPs persisting after cessation of heparin anticoagulation.

PMID- 7563404
TI  - Prospective evaluation of peripheral vascular disease in heart transplant
      recipients.
AB  - PURPOSE: Retrospective reviews suggest that the progression of peripheral
      vascular disease (PVD) may be accelerated in heart transplant recipients. This
      study was undertaken to determine the incidence and to identify those risk
      factors that may be associated with the development or progression of PVD in
      these patients. METHODS: Between January 1990 and December 1993 a prospective
      vascular screening protocol including abdominal ultrasonography, Doppler-derived
      ankel-brachial pressure indexes (ABI), and carotid artery duplex imaging was
      added to the routine preoperative and annual postoperative evaluation of 239
      heart transplant recipients. RESULTS: Thirty-one significant vascular lesions
      were detected in 10% (24 of 239) of patients 52 +/- 9 years of age at a mean of
      3.2 years after transplant. The distribution of lesions included carotid artery
      stenosis (11), femoropopliteal occlusive disease (10), aortoiliac occlusive
      disease (five), aortic aneurysm (four), and renal artery stenosis in one patient.
      Revascularization procedures were performed in 12 (50%) patients (carotid
      endarterectomy (four), aortobifemoral bypass grafting (three), abdominal aortic
      aneurysm repair (two), transluminal angioplasty (two), splenorenal bypass (one),
      and femorotibial bypass grafting (one)). One patient with diabetes mellitus (DM)
      was found to have noncompressible vessels during pretransplant evaluation. An
      additional 26 patients (11%), seven with DM, had noncompressible vessels in the
      lower extremities during the follow-up period. Logistic regression analysis
      revealed that the development of posttransplant PVD was associated with smoking
      (p < 0.05) and ischemic cardiomyopathy as an indication for transplantation (p <
      0.05). The development of noncompressible vessels was associated with younger age
      (p < 0.05) and the presence of diabetes (p < 0.05). CONCLUSION: Posttransplant
      peripheral vascular disease occurred in 10% of heart transplant recipients and is
      associated with pretransplant ischemic cardiomyopathy and smoking. A previously
      unrecognized subgroup of patients who have noncompressible vessels after
      operation is described. If the long-term survival of the heart transplant
      recipient is to be improved, routine follow-up to identify and treat those
      patients at greater risk appears justified.

PMID- 7563405
TI  - Essential thrombocytosis: underemphasized cause of large-vessel thrombosis.
AB  - PURPOSE: The purpose of this study was to describe the clinical course of
      patients seen with large-vessel thrombosis in association with essential
      thrombocytosis (ET). METHODS: This study was a retrospective review of all
      patients treated for large-vessel thrombosis caused by ET during a 2-year period
      at University of Washington teaching hospitals. RESULTS: Five patients presented
      with arterial (femoral-popliteal-tibial: aortic), portal (two cases), or systemic
      venous (inferior vena cava) thrombosis and required operation. Two were known to
      have ET; in three others ET was diagnosed after operation when platelet counts
      persistently in excess of 500,000/mm3 were noted. The diagnosis of ET was
      established in each case by ruling out causes of reactive thrombocytosis and (in
      the three new cases) by evidence for megakaryocyte hyperplasia on bone marrow
      biopsy. Platelet counts in all five patients were reduced to normal levels by
      cytoreductive therapy, and no further thrombotic episodes have occurred during 18
      months (mean) of follow-up. During this 2-year period ET accounted for more large
      vessel thrombotic complications in our institutions than all other more
      frequently described hypercoagulable states combined. CONCLUSIONS: ET is an
      underemphasized cause of large-vessel thrombosis.

PMID- 7563406
TI  - Progression of atherosclerosis in arteries distal to lower extremity
      revascularizations.
AB  - PURPOSE: The characteristics of progression of atherosclerotic occlusive disease
      (AOD) of the lower extremities after revascularization are unknown. Duplex
      scanning or angiography were used to determine progression in 150 patients after
      they underwent revascularization for AOD. METHODS: Follow-up studies were
      compared with presurgical arteriograms. Superficial femoral (SFA) and popliteal
      arteries were graded as less than 50% stenosis, 50% to 99% stenosis, or occluded.
      Tibial arteries were graded with regard to whether they were continuously patent
      from the popliteal trifurcation to the ankle. Progression was defined as an
      increase in one stenosis category. RESULTS: At a mean follow-up of 4.8 years, 18%
      of native arteries, 39% of extremities, and 52% of patients demonstrated
      progression of AOD. Overall, 21% of arteries in patients undergoing infrainguinal
      bypass and 14% of arteries in patients undergoing suprainguinal bypass
      demonstrated progression (p = 0.004). Progression was more frequently detected in
      examinations performed more than 4 years after baseline arteriography (66%) than
      in examinations performed 6 months to 2 years (45%, p = 0.032) or 2 to 4 years
      (44%, p = 0.029) after baseline arteriography. Thirty percent of SFAs
      demonstrated progression, and 32% with 50% stenosis or greater at baseline became
      occluded. There was no difference in SFA, popliteal, or tibial artery progression
      in revascularized versus nonrevascularized extremities after suprainguinal
      bypass. There was no difference in tibial artery progression in operated and
      nonoperated limbs after femoropopliteal artery bypass. CONCLUSIONS: AOD
      progression occurs frequently in patients requiring revascularization and is more
      prevalent in patients requiring femoropopliteal than in patients requiring
      suprainguinal bypass. AOD progression in patients undergoing vascular surgery is
      associated with the pattern of disease producing lower extremity ischemia and
      does not appear to be worsened by arterial reconstruction.

PMID- 7563408
TI  - Vein graft lesions: time of onset and rate of progression.
AB  - PURPOSE: The objectives of this study were to determine the time of onset,
      location, severity, rate of progression, and subsequent fate of infrainguinal
      vein graft lesions. METHODS: Sixty-one infrainguinal vein grafts were studied
      serially with duplex ultrasonography to document the location and severity of
      each lesion. Grafts were studied at 1, 2, 3, 4, 6, 9, 12, and 18 months and then
      annually. RESULTS: The cumulative secondary graft patency rate at 3 years (life
      table analysis) was 93.2%. A total of 158 lesions were detected in 55 of the 61
      grafts studied. The degree of diameter reduction at the time of initial detection
      was as follows: 1% to 19% (29.6%), 20% to 49% (51.0%), 50% to 75% (17.3%), and
      greater than 75% (3.1%). Forty-eight percent were detected at the first
      examination, 59.2% within 2 months, and 85.7% within 6 months. Progression was
      detected in 31.2% of the lesions by 6 and in 39.1% of the lesions by 18 months
      (life-table analysis). Thrombosis, in the absence of significant changes in ankle
      brachial index (> or = 0.15) or return of symptoms, was not observed in grafts
      that had lesions with less than 75% diameter reduction. CONCLUSIONS: The data
      support the performance of a duplex scan either during surgery or before
      discharge from the hospital in addition to frequent surveillance for the first 6
      months. Frequent surveillance is appropriate for lesions with less than 75%
      diameter reduction as long as they remain asymptomatic and without a significant
      reduction in the ankle-brachial index.

PMID- 7563407
TI  - Should percutaneous transluminal angioplasty be recommended for treatment of
      infrageniculate popliteal artery or tibioperoneal trunk stenosis?
AB  - PURPOSE: The purpose of this study was to determine the effectiveness of
      percutaneous transluminal angioplasty (PTA) for treatment of patients with
      localized stenosis of the infrageniculate popliteal artery and tibio-peroneal
      trunk (IGPA). METHODS: The records of 25 patients undergoing IGPA PTA from 1983
      to 1993 were reviewed. Patients underwent follow-up with clinical examinations,
      ankle-brachial indexes, Duplex scanning, and arteriography. Demographic variables
      and cardiovascular risk factors were analyzed and correlated with outcome.
      RESULTS: Mean follow-up was 44 months. With life-table analysis, clinical and
      hemodynamic success was 59%, 32%, and 20% at 1, 2, and 3 years, respectively.
      Average time to recurrence was 17 months. Sixteen patients required a subsequent
      procedure; two had only repeat PTA, six had repeat PTA followed by arterial
      bypass, and eight had bypass alone. The mean additional benefit of repeat PTA was
      8 months. Eleven of the 14 patients treated with bypass became symptom-free with
      patent grafts at a mean follow-up of 52 months. No risk factor was statistically
      significant in predicting success of IGPA PTA. CONCLUSIONS: IGPA PTA is an
      expensive temporizing measure with a high rate of recurrence requiring subsequent
      intervention. The procedure should be restricted to patients with limited life
      expectancy or contraindications to operation.

PMID- 7563409
TI  - Do normal early color-flow duplex surveillance examination results of
      infrainguinal vein grafts preclude the need for late graft revision?
AB  - PURPOSE: Optimal duration of postoperative duplex surveillance of infrainguinal
      vein grafts is not known. Previous reports have suggested nearly all vein graft
      stenoses are present within the first postoperative year, and normal duplex
      examination results during this time eliminate the need for ongoing graft
      surveillance. To determine whether surveillance may be safely discontinued in
      patients with normal early postoperative surveillance studies, we reviewed the
      color-flow surveillance examinations in our patients who underwent infrainguinal
      reverse vein graft revisions during a 4 1/2 year period. METHODS: Clinical and
      vascular laboratory records were reviewed of all patients who underwent
      infrainguinal reverse vein bypass grafting followed by subsequent graft revision
      for a duplex scanning-detected abnormality at our institution between January
      1990 and July 1994. RESULTS: Of 447 infrainguinal reverse vein bypasses
      performed, 36 (8.1%) underwent surgical revision as a result of an abnormal
      finding during routine duplex surveillance. The initial postoperative duplex
      examination was obtained within 2 weeks of graft implantation in 23 (64%)
      patients, between 2 weeks and 3 months in 10 (28%) patients, and between 3 and 6
      months in three (8%) patients. Duplex abnormalities prompting revision included
      11 (31%) grafts with a mid-graft peak systolic velocity (PSV) < or = 45 cm/sec,
      23 (64%) grafts with a focal PSV > or = 200 cm/sec, one graft with a PSV > or =
      150 cm/sec but < 200 cm/sec, and one thought to be occluded by duplex but found
      to be patent by angiography. Abnormal duplex findings were initially detected
      within 2 weeks of graft implantation in five (14%) patients, between 2 weeks and
      3 months in eight (22%) patients, from 3 to 6 months in 12 (33%) patients, from 6
      to 12 months in six (17%) patients, and > 1 year in five (14%) patients. In only
      25% of cases were mid-graft PSVs < or = 45 cm/sec or focal velocities > or = 200
      cm/sec identified on the initial examination; 75% were found during subsequent
      surveillance. CONCLUSIONS: Although most reverse vein graft abnormalities
      detected by duplex surveillance and prompting graft revision appear within the
      first postoperative year, many are not detected on the initial examination. In
      our recent experience 31% of duplex abnormalities leading to vein graft revision
      were first detected more than 6 months after operation. Discontinuation of graft
      surveillance based on normal early findings will result in thrombosis of some
      vein grafts that may otherwise be salvaged.

PMID- 7563410
TI  - A prospective evaluation of transcutaneous oxygen measurements in the management
      of diabetic foot problems.
AB  - PURPOSE: To test the hypothesis that lower extremity transcutaneous oxygen
      (TcPO2) measurements can accurately predict severity of foot ischemia and can be
      used to select appropriate treatment (conservative versus operative) for patients
      with diabetes and tissue necrosis or ischemic rest pain. METHODS: Fifty-five
      patients with 66 limbs were prospectively treated from June 1993 to July 1994.
      Noninvasive hemodynamic arterial assessment and TcPO2 mapping of the involved
      limb were obtained before treatment was selected. If the transmetatarsal TcPO2
      level was 30 mm Hg or greater, the patient's foot problem was managed
      conservatively with local wound care, debridement, or a minor foot amputation. If
      the transmetatarsal TcPO2 level was less than 30 mm Hg, arteriography was
      performed with the anticipated need for vascular reconstruction. The endpoints
      for determining treatment success or failure were complete wound healing or
      relief of ischemic rest pain. RESULTS: Thirty-one of 36 (86%) limbs with an
      initial transmetatarsal TcPO2 level of 30 mm Hg or greater were treated
      successfully with conservative care, including 73% (11 of 15 feet) of limbs
      without a palpable pedal pulse. After either bypass or angioplasty, 20 of 24
      (83%) limbs achieved a transmetatarsal TcPO2 level greater than 30 mm Hg and had
      complete resolution of their presenting foot problem. An initial or
      postintervention transmetatarsal TcPO2 level of 30 mm Hg or greater was more
      accurate (90%, p = 0.001) than a palpable pedal pulse (65%, p = 0.009), in
      predicting ultimate wound healing or resolution of rest pain. CONCLUSIONS: TcPO2
      mapping is a useful noninvasive modality that can prospectively determine
      severity of foot ischemia, aid in selecting appropriate treatment for patients
      with diabetes and foot salvage problems, and decrease the total cost of such
      care.

PMID- 7563411
TI  - Clostridium septicum bacteremia associated with aortic graft infection.
AB  - After emergency repair of a ruptured abdominal aortic aneurysm associated with an
      aortocaval fistula, Clostridium septicum sepsis prompted evaluation for colon
      cancer. Adenocarcinoma of the right colon ultimately required hemicolectomy,
      after which the patient had development of recurrent C. septicum bacteremia.
      Computed tomography scanning demonstrated a large fluid collection surrounding
      the aortic graft, and percutaneous drainage documented recurrent C. septicum.
      Initial axillobifemoral bypass was followed by removal of the patient's aortic
      graft and retroperitoneal drainage. After 3 years the patient is without evidence
      of recurrent infection or tumor. This case report consists of a known instance of
      C. septicum infection of an aortic graft.

PMID- 7563412
TI  - Leiomyosarcoma of the subclavian artery.

PMID- 7563413
TI  - Bidirectional vena cava filter placement.

PMID- 7563414
TI  - The Western Vascular Society: its first ten years.

PMID- 7563415
TI  - Serologic survey of neotropical bats in Guatemala for virus antibodies.
AB  - Neotropical bats were collected from different life zones in Guatemala in 1983
      and 1984 to determine the presence and distribution of antibody against 10
      viruses. Bats were collected with mist nets at 13 sites in eight departments and
      332 serum specimens were obtained for testing for neutralizing (N) antibody by
      the plaque-reduction neutralization test. Eighty-seven (26%) of the 332 bats from
      16 (38%) of 42 bat species sampled were serologically positive for five of six
      arboviruses and for two other viruses tested. Antibodies against Venezuelan
      equine encephalitis (VEE) variant I-A/B, eastern equine encephalitis, western
      equine encephalitis, St. Louis encephalitis, vesicular stomatitis, Tacaribe, and
      Rio Bravo viruses were detected in resident species of bats. However, N
      antibodies against the enzootic strain of VEE (Mena II, variant I-E) or Nepuyo
      viruses were not detected.

PMID- 7563416
TI  - Antibodies to St. Louis encephalitis virus in armadillos from southern Florida.
AB  - From January 1990 through March 1991, 189 armadillos (Dasypus novemcinctus) were
      collected from Brevard and Glades Counties in southern Florida (USA). The sera
      were analyzed for hemagglutination-inhibition (HAI) antibodies against St. Louis
      encephalitis (SLE) and eastern equine encephalomyelitis (EEE) viruses. None of
      the armadillos had detectable HAI antibody to EEE virus, but 59 (31%) had
      antibodies against SLE virus. Sera from 31 of the HAI-positive armadillos
      contained significant levels of neutralizing (NT) antibody to SLE virus.
      Armadillos captured during the 1990 SLE human epidemic in south Florida had a
      greater prevalence of HAI and NT antibody to SLE virus than did animals captured
      before the start of the epidemic. This is evidence that armadillos were fed on by
      mosquitoes infected with SLE virus. We propose that armadillos may be involved in
      the SLE amplification and transmission cycles in Florida.

PMID- 7563417
TI  - Carfentanil, bison, and statistics: the last word?

PMID- 7563418
TI  - Brucellosis in captive bison.

PMID- 7563419
TI  - Prevalence of antibodies to Toxoplasma gondii in wild mammals of Missouri and
      east central Kansas: biologic and ecologic considerations of transmission.
AB  - Sera from 273 wild mammals from Missouri and Kansas (USA), collected between
      December 1974 and December 1987, were tested for the presence of antibodies to
      Toxoplasma gondii using the Sabin-Feldman dye test. Sixty-five (24%) had
      antibodies at titers of > or = 1:8, including 38 (66%) of 58 carnivores, 14 (15%)
      of 94 omnivores, 13 (11%) of 117 herbivores, and none of four insectivores. The
      prevalence of antibodies in mice (Mus musculus and Peromyscus spp.) and rats
      (Rattus norvegicus and Sigmodon hispidus) was low (3%), while medium sized
      herbivores such as squirrels (Sciurus spp.), rabbits (Sylvilagus floridanus), and
      muskrats (Ondatra zibethicus) had prevalences of about 18%. Red foxes (Vulpes
      fulva) and mink (Mustela vison) had the highest prevalence of antibodies with
      frequencies of 90 and 66%, respectively. In 32 attempts to isolate Toxoplasma
      gondii from wild mammals with positive (> or = 1:4) titers, only six (19%) were
      successful: a gray squirrel (Sciurus carolinensis), a beaver (Castor canadensis),
      an opossum (Didelphis marsupialis), a red fox and two mink. These findings are
      consistent with the hypothesis that the probability of infection with Toxoplasma
      gondii, and therefore prevalence of antibodies in wildlife, is greatest in
      carnivores.

PMID- 7563420
TI  - Molecular characterization of Pasteurella testudinis isolated from desert
      tortoises (Gopherus agassizii) with and without upper respiratory tract disease.
AB  - Isolates of Pasteurella testudinis recovered from clinically healthy desert
      tortoises (Gopherus agassizii) and tortoises with upper respiratory tract disease
      (URTD) were characterized in an attempt to identify strains associated with
      disease. Eighty-nine isolates, 52 from ill and 37 from healthy tortoises
      collected from Nevada (USA), June 1990 to September 1991, were genomically
      fingerprinted and grouped based on ribotype similarity. Twelve isolates (six from
      ill and six from healthy tortoises) were further characterized with regard to
      whole-cell protein (WCP) and outer membrane protein (OMP) composition and their
      ability to survive in normal tortoise plasma. The 89 isolates were initially
      distributed into 33 distinct ribotype groups using the restriction enzyme EcoRI;
      five ribotypes contained over 50% of the isolates. Only one EcoRI ribotype was
      comprised of multiple isolates (n = 4) exclusively recovered from tortoises with
      URTD. When the ten EcoRI ribotypes that contained more than one isolate per
      ribotype were further studied using a second restriction enzyme, EcoRV, one
      EcoRI/EcoRV ribotype contained five isolates recovered from URTD tortoises and
      none from healthy animals. The EcoRI ribotype comprised of four isolates, all
      from tortoises with URTD, was further separated into three distinct groups with
      EcoRV. All 12 isolates studied grew equally well in normal tortoise plasma, and
      when broth-grown WCP and OMP profiles were evaluated, no proteins were unique to
      isolates from URTD tortoises. Iron-regulated OMP's were produced in three
      isolates examined, but these OMP's apparently were not virulence-related.

PMID- 7563421
TI  - An epizootic of hemorrhagic disease in white-tailed deer (Odocoileus virginianus)
      in Missouri: necropsy findings and population impact.
AB  - An epizootic occurred among white-tailed deer (Odocoileus virginianus) from July
      through October 1988 in Missouri (USA). From late July through September, nine
      necropsied deer had lesions of the peracute or acute forms of hemorrhagic disease
      (HD) or no apparent lesions, whereas two deer necropsied in October had lesions
      of the chronic form of HD. Epizootic hemorrhagic disease virus was isolated from
      two necropsied deer. Based on changes in population indices, there is evidence
      that deer populations declined in seven of Missouri's 57 deer management units
      from 1987 to 1990. Based on a deterministic model designed to simulate deer
      populations in management units, it appeared that summer and fall 1988 mortality
      ranging from 6% to 16% accounted for the population decreases in deer management
      units with population declines. Heavily hunted areas where high deer mortality
      was not reported in the summer and fall of 1988 did not have population declines.
      Based on these results, we believe that HD mortality was high and resulted in
      deer population declines in parts of Missouri when combined with hunting harvest.

PMID- 7563422
TI  - Capture of wood bison (Bison bison athabascae) using carfentanil-based mixtures.
AB  - Between 1986 and 1991, 155 wood bison (Bison bison athabascae) (33 adult females,
      92 adult males, twelve 6 mo-old calves, eighteen 1 to 2 mo-old calves) in the
      Mackenzie Bison Sanctuary, Northwest Territories, Canada, and adjacent area were
      captured by dart immobilization. Initial trials with carfentanil, xylazine and
      R51163 as immobilizing agents were conducted. Subsequently, carfentanil alone, or
      in combination with xylazine, was used. Small doses of xylazine were used when
      required to control head and hind limb movement of recumbent bison. The mean dose
      of carfentanil used was 7.0 micrograms/kg. Narcotic antagonists used were
      naltrexone, naloxone and M5050. Narcotic recycling was seen in animals treated
      with naloxone and low doses of naltrexone. Furthermore recycling was suspected in
      the deaths of several animals treated with these antagonist regimes. No recycling
      was seen when doses of naltrexone in excess of 90:1 naltrexone:carfentanil were
      used. We recommend using a naltrexone:carfentanil dose in excess of 125:1 to
      ensure uneventful recovery.

PMID- 7563423
TI  - Immobilization of ocelots and bobcats with ketamine hydrochloride and xylazine
      hydrochloride.
AB  - We immobilized 10 ocelots (Felis pardalis), and 21 bobcats (F. rufus) in south
      Texas (USA) during March to November 1991 with a mixture of ketamine
      hydrochloride (KH) and xylazine hydrochloride (XH); two ocelots were immobilized
      twice. Species were immobilized with (mean +/- SE) 14.7 +/- 1.6 mg KH/kg body
      mass for ocelots, 13.3 +/- 1.8 mg KH/kg for bobcats, and 1.1 +/- 0.1 mg XH/kg and
      1.2 +/- 0.1 mg XH/kg for ocelots and bobcats, respectively. Immobilization times
      in bobcats were longer (P = 0.08) than in ocelots. Adult female ocelots (18.5 +/-
      2.6 mg/kg) needed larger (P < 0.05) doses of KH than adult males (12.0 +/- 1.7
      mg/kg). Bobcats were immobilized during summer with lower initial (8.6 +/- 0.9
      mg/kg, P < 0.001) and total (10.1 +/- 1.3 mg/kg, P = 0.02) doses of KH than
      bobcats immobilized in winter (14.5 +/- 1.0 mg/kg, and 18.5 +/- 3.8 mg/kg,
      respectively); summer immobilization times (44.3 +/- 3.8 min) were also shorter
      (P = 0.03) than during winter (59.1 +/- 5.2 min). Bobcats immobilized during
      summer had lower (P < 0.01) initial rectal temperatures (39.4 +/- 0.2 C) than
      bobcats trapped in winter (41.1 +/- 0.4 C). Overall, we observed no effects of KH
      XH dose on body temperature.

PMID- 7563424
TI  - Heavy metals in some species of waterfowl of northern Italy.
AB  - Concentrations of heavy metals (zinc, copper, cadmium, and iron) were measured in
      several tissues (brain, gizzard, leg-muscle, heart, breast-muscle, intestine,
      liver and kidney) of moorhens (Gallinula chloropus), black-headed gulls (Larus
      ridibundus), and coots (Fulica atra) collected between autumn 1985 and spring
      1989 in northern Italy. Cadmium concentrations in the liver and kidney of water
      rails (Rallus aquaticus) and in five species of Anatidae collected also were
      measured. High mean (+/- SD) copper levels were detected in aerobic muscles such
      as heart (38 +/- 5 micrograms/g dry weight (DW)) and pectoral muscles (35 +/- 7
      micrograms/g DW). Compared to other tissues, the iron content of brain was rather
      low and constant, with a mean value of 160 +/- 17 micrograms/g DW in moorhens,
      157 +/- 60 micrograms/g DW in black-headed gulls, and 157 +/- 25 micrograms/g DW
      in coots. Iron concentrations in tissues of moorhens from the Reno River were
      significantly higher than those from the Sile River. Cadmium was detectable only
      in the liver and kidney; there was a linear relationship between cadmium levels
      in these two organs. The highest mean (+/- SD) cadmium concentrations were
      present in the kidney of black-headed gull (30 +/- 20 micrograms/g DW).

PMID- 7563425
TI  - A humane killing trap for lynx (Felis lynx): the Conibear 330 with clamping bars.
AB  - The Conibear 330 failed to render irreversibly unconscious in < or = 3 min one
      lynx (Felis lynx) struck in the shoulders and two of eight lynx struck in the
      neck region, in simulated natural environments. A Conibear 330 with two clamping
      bars rendered unconscious in < or = 3 min eight lynx struck in the neck and one
      struck in the shoulders. The mean (+/- SE) times to loss of consciousness and
      heartbeat were 67.2 (+/- 4.0) sec and 196.0 (+/- 10.4) sec, respectively. This
      modified Conibear 330 can be expected to render > or = 70% of captured lynx
      irreversibly unconscious in < or = 3 min (P < 0.05).

PMID- 7563426
TI  - Efficacy of ivermectin pour-on against Ostertagia ostertagi infection and
      residues in the American bison, Bison bison.
AB  - Sixteen American bison, Bison bison, were artificially infected with 10(5)
      infective stage larvae of Ostertagia ostertagi on 21 April 1993. At 42 days post
      infection eight bison were treated with 0.5% ivermectin pour-on (500
      micrograms/kg bodyweight) and eight treated with the carrier only. Bison were
      necropsied 17 and 18 days post-treatment (21 and 22 June 1993, respectively).
      Mean (+/- SE) of 5,413 (+/- 1,716) adults and 565 (+/- 305) immature O. ostertagi
      were recovered at necropsy from bison treated with the carrier. No O. ostertagi
      were detected in bison treated with ivermectin pour-on. Based on the levels of
      the ivermectin marker metabolite in liver and adipose tissue 18 days post
      treatment, the established bovine withdrawal time of 48 days appears adequate to
      insure that violative residues do not occur.

PMID- 7563427
TI  - Serological survey for avian paramyxoviruses from wildfowl in aquatic habitats in
      Andalusia.
AB  - A serological survey for a range of avian paramyxoviruses (PMV) was carried out
      among wildfowl from southern Spain, 1990 to 1992, using the hemagglutination
      inhibition technique. We collected 579 sera from 24 avian families (18 aquatic
      and six non-aquatic). Antibodies were detected to all paramyxoviruses in
      waterfowl, with a notable prevalence of antibodies to PMV-8 (43%) and to a lesser
      extent PMV-6 (21%). By contrast, in non-aquatic species high antibody prevalences
      were detected only to PMV-2 (60%), particularly in sparrows (68%), while antibody
      prevalences to other PMV's were moderate or low.

PMID- 7563429
TI  - Fulminant Streptococcus pneumoniae meningitis in a lion-tailed macaque (Macaca
      silenus) without detected signs.
AB  - A 3-month-old lion-tailed macaque (Macaca silenus) infant that died on 2 February
      1985 in the Baltimore Zoo (Baltimore, Maryland, USA) due to fulminating
      Streptococcus pneumoniae meningitis had congested, edematous lungs, and thickened
      and congested brain leptomeninges with a grayish-yellow fluid within the
      subarachnoid brain space. From bacterial cultures made postmortem of the
      subarachnoid brain space fluid, cerebrospinal fluid, throat secretions, nasal
      secretions, and lung fluid, we isolated pure cultures of group B streptococci,
      alpha hemolytic S. pneumoniae, type 19F (capsular). We also isolated
      Staphylococcus aureus and S. hemolytica from antemortem nasal and throat
      bacterial cultures from all 13 animals of the M. silenus colony. Streptococcus
      pneumoniae meningitis in M. silenus has not been previously reported.

PMID- 7563430
TI  - Occurrence of rabies in a wolf population in northeastern Alaska.
AB  - Nine Alaskan wolves (Canis lupus) were found dead during spring and summer 1985;
      five of seven animals tested for rabies virus were positive. The 1985 epizootic
      altered annual den use patterns by wolves in northeastern Alaska, but did not
      appear to affect population size. We propose that rabies in arctic wolves may be
      more common than previously thought.

PMID- 7563428
TI  - Lentivirus infection in an African lion: a clinical, pathologic and virologic
      study.
AB  - In May 1991, clinical, pathologic, and virologic investigations were carried out
      on an 8-yr-old male lion (Panthera leo), with recurrent infections, in captivity
      with two lionesses in the Zoological Garden of Pistoia, Tuscany, Italy. The lion
      had severe pneumonia, neutropenia, thrombocytopenia, and an increase in blood
      urea nitrogen and creatininemia; in spite of therapy, it died within 3 months. At
      necropsy, the animal had a lymphoma and other lesions similar to those described
      in feline immunodeficiency virus-infected cats. We identified FIV gag-sequence
      using PCR amplification of lymph node tissues.

PMID- 7563431
TI  - Tuberculosis in a wild Australian fur seal (Arctocephalus pusillus doriferus)
      from Tasmania.
AB  - Tuberculosis was found in a wild, mature male Australian fur seal (Arctocephalus
      pusillus doriferus) at Hobart, Tasmania on 8 March 1992. We observed
      fibrogranulomatous and pyogranulomatous lesions in the lung, pleura, lymph nodes
      and spleen. The SDS/PAGE profile of this Tasmanian isolate was similar to other
      seal strains; however, differences were detected using pTBN12 and insertion
      sequence IS6110 probes.

PMID- 7563432
TI  - Trichomoniasis as a factor in mourning dove population decline in Fillmore, Utah.
AB  - We examined whether trichomoniasis had been a factor in a dramatic mourning dove
      (Zenaida macroura) population decline in Fillmore, Utah (USA). We reasoned that
      if we could not find a high proportion of doves showing clinical signs of disease
      then the population was not being affected. Prevalences of Trichomonas gallinae
      in doves were 21% for 1992 and 14% for 1993. We also examined 230 birds and found
      only one with oral lesions. These prevalences were similar to those observed at
      the same study site in the 1950's, or reported elsewhere. Based on our results,
      we believe that trichomoniasis was not affecting the Fillmore mourning dove
      population at the time of our study.

PMID- 7563433
TI  - Survey for blood parasites in redheads (Aythya americana) wintering at the
      Chandeleur Islands, Louisiana.
AB  - We detected no infections with species of Plasmodium, Haemoproteus,
      Leucocytozoon, Sarcocystis or Trypanosoma in blood smears, liver and spleen
      impressions, and muscle tissue from 136 redheads (Aythya americana) collected or
      captured at the Chandeleur Islands, Louisiana (USA), during three winters (1987
      to 1990). One bird, a juvenile male, was infected with an unidentified species of
      microfilaria. Thus, we found no evidence that hematozoa had an effect on redheads
      during the course of the study.

PMID- 7563434
TI  - A practical method for cleaning Baermann glassware.
AB  - When using the Baermann technique to detect larvae of Parelaphostrongylus tenuis
      in deer feces, it is difficult to ensure that no larvae remain on glassware
      between samples. Of several cleaning methods tested here, emersion in 95% ethanol
      after flushing with hot or cold water was the most effective and practical.

PMID- 7563436
TI  - Exclusion of copper from altered hepatocytes in white perch (Morone americana)
      with hepatic copper storage.
AB  - Iron is excluded from foci of hepatocellular alteration in carcinogenesis of
      rodents and some fish. Among white perch (Morone americana), there is a condition
      of hepatic copper storage in which copper-loaded livers are produced naturally.
      In a group of fish collected from the Chesapeake Bay, Maryland (USA), from
      September to December 1990, we observed hepatic lesions which excluded copper
      similar to the phenomenon of iron exclusion, in a white perch with over 3,600
      micrograms/g wet weight hepatic copper. The lesions were of two types: one with
      cells morphologically different from normal hepatocytes and which had diminished
      to absolute exclusion of copper with the copper specific histochemical stain
      rubeinic acid, and a second with cells morphologically similar to normal
      hepatocytes which had only a partial exclusion of copper. Although the exact
      cause and nature of the lesions was not determined, intrinsic copper toxicity,
      environmental pollution, or a combination of these factors may have contributed
      to their development.

PMID- 7563435
TI  - Hematology of fledgling Manx shearwaters (Puffinus puffinus) with and without
      'puffinosis'.
AB  - Hematological parameters were measured in 14 fledgling Manx shearwaters (Puffinus
      puffinus), with the disease puffinosis and in 10 birds that did not have the
      disease, on the Island of Skomer between 2 and 11 September 1991. The mean plasma
      fibrinogen concentration was significantly higher in the diseased birds and some
      of these had abnormally elevated monocyte counts. No other significant
      differences were observed.

PMID- 7563437
TI  - Computer-based medical translator system helps bridge language gap between
      physician, patient.

PMID- 7563438
TI  - Inner-city asthma control campaign under way.

PMID- 7563439
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      worldwide, 1995.

PMID- 7563440
TI  - From the Centers for Disease Control and Prevention. Update: HIV-2 infection
      among blood and plasma donors--United States, June 1992-June 1995.

PMID- 7563441
TI  - Treatment guidelines for hyperthyroidism and hypothyroidism.

PMID- 7563442
TI  - Treatment guidelines for hyperthyroidism and hypothyroidism.

PMID- 7563443
TI  - Treatment guidelines for hyperthyroidism and hypothyroidism.

PMID- 7563445
TI  - If almost nothing goes wrong, is almost everything all right? Interpreting small
      numerators.

PMID- 7563444
TI  - Optimal calcium intake.

PMID- 7563447
TI  - Nursing care and development of pressure ulcers.

PMID- 7563446
TI  - Cost-effectiveness of noninvasive testing for osteomyelitis.

PMID- 7563448
TI  - And then there were none: the demise of national medical television.

PMID- 7563449
TI  - And then there were none: the demise of national medical television.

PMID- 7563450
TI  - The naturalness of dying.

PMID- 7563451
TI  - Intravenous thrombolysis with recombinant tissue plasminogen activator for acute
      hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS)
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravenous thrombolysis using
      recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic
      stroke. DESIGN: Randomized, prospective, multicenter, double-blind, placebo
      controlled clinical trial. SETTING: A total of 75 hospitals in 14 European
      countries. PATIENTS: A total of 620 patients with acute ischemic hemispheric
      stroke and moderate to severe neurologic deficit and without major early infarct
      signs on initial computed tomography (CT). INTERVENTION: Patients were randomized
      to treatment with 1.1 mg per kilogram of body weight of rt-PA (alteplase) or
      placebo within 6 hours from the onset of symptoms. OUTCOME MEASURES: Primary end
      points included Barthel Index (BI) and modified Rankin Scale (RS) at 90 days.
      Secondary end points included combined BI and RS, Scandinavian Stroke Scale (SSS)
      at 90 days, and 30-day mortality. Tertiary end points included early neurologic
      recovery (SSS) and duration of in-hospital stay. Safety parameters included
      mortality and incidence of intracranial or extracranial hemorrhage. RESULTS: The
      distribution of demographic variables was similar among patients in the rt-PA and
      placebo treatment arms in both the intention-to-treat (ITT) analysis and the
      explanatory analysis for the target population (TP). A total of 109 patients
      (17.4%) were included in the trial despite major protocol violations but excluded
      from the TP. There was no difference in the primary end points in the ITT
      analysis, while the TP analysis revealed a significant difference in the RS in
      favor of rt-PA-treated patients (P = .035). Of the secondary end points, the
      combined BI and RS showed a difference in favor of rt-PA-treated patients in both
      analyses (P < .001). Neurologic recovery at 90 days was significantly better for
      rt-PA-treated patients in the TP (P = .03). The speed of neurologic recovery
      assessed by the SSS was significantly better up to 7 days in the ITT analysis and
      up to 30 days for the TP in the rt-PA treatment arm. In-hospital stay was
      significantly shorter in the rt-PA treatment arm in both analyses. There were no
      statistically significant differences in the mortality rate at 30 days or in the
      overall incidence of intracerebral hemorrhages among the rt-PA and placebo
      treatment arms in either analysis. However, the occurrence of large parenchymal
      hemorrhages was significantly more frequent in the rt-PA-treated patients.
      CONCLUSIONS: Intravenous thrombolysis in acute ischemic stroke is effective in
      improving some functional measures and neurologic outcome in a defined subgroup
      of stroke patients with moderate to severe neurologic deficit and without
      extended infarct signs on the initial CT scan. However, the identification of
      this subgroup is difficult and depends on recognition of early major CT signs of
      early infarction. Therefore, since treating ineligible patients is associated
      with an unacceptable increase of hemorrhagic complications and death, intravenous
      thrombolysis cannot currently be recommended for use in an unselected population
      of acute ischemic stroke patients.

PMID- 7563452
TI  - Relationship between driver's license renewal policies and fatal crashes
      involving drivers 70 years or older.
AB  - OBJECTIVE: To assess the relationship between state driver's license renewal
      policies and fatal crashes involving drivers aged 70 years or older (seniors).
      DESIGN AND ANALYSIS: Poisson regression methods were used to isolate the
      relationship between different state policies mandating vision tests, knowledge
      tests, or road tests for driver's license renewal and fatal crashes involving
      senior drivers. The analysis controlled for differences among states, other than
      their renewal policies, likely to influence senior motor vehicle crashes.
      SETTING: United States, 1985 through 1989. PARTICIPANTS: All fatal crashes
      identified in the National Highway Traffic Safety Administration Fatal Accident
      Reporting System involving at least one driver aged 70 years or older. MAIN
      OUTCOME MEASURE: The number of fatal crashes per state in which at least one of
      the drivers was aged 70 years or older. When a single fatal crash involved more
      than one senior driver, each was included. RESULTS: State-mandated tests of
      visual acuity, adjusted for license renewal period, were associated with lower
      fatal crash risk for senior drivers (relative risk, 0.93; 95% confidence
      interval, 0.89 to 0.97). Knowledge tests, when added to vision tests and applied
      only to seniors, provided a nonsignificant reduction in the senior fatal crash
      risk (relative risk, 0.91; 95% confidence interval, 0.79 to 1.05). CONCLUSION:
      Tests of vision and knowledge for senior drivers at license renewal merit further
      attention as a means of improving senior traffic safety.

PMID- 7563453
TI  - The epidemic of gang-related homicides in Los Angeles County from 1979 through
      1994.
AB  - OBJECTIVE: To determine trends in gang homicides and the population at greatest
      risk for homicide by reviewing all gang-related homicides in Los Angeles County,
      California, from January 1979 to December 1994. DESIGN: Homicide files of the Los
      Angeles Police Department and the Los Angeles County Sheriff's Department from
      1979 to 1994 involving violent street gang activity were reviewed. Gang files
      were reviewed for demographic data, weapons used, homicides by drive-by
      shootings, and times and geographic areas of occurrence. SETTING: Los Angeles
      County from January 1, 1979, to December 31, 1994. MAIN OUTCOME MEASURES: Age,
      race, and sex of gang-related homicide victims; frequency of weapon use; and the
      change in gang-related homicide rates during the study period. RESULTS: A total
      of 7288 gang-related homicides occurred in Los Angeles County from 1979 through
      1994; 5541 of these homicides occurred in Los Angeles Police Department and Los
      Angeles County Sheriff's Department jurisdictions. During the study period, the
      proportion of all homicides that were gang related increased from 18.1% to 43.0%
      (P < .001). Of the 5541 gang-related homicide victims, 4580 (85.6%) were aged 15
      to 34 years, 93.3% were African American or Hispanic, 5157 (93.2%) were male,
      3559 (64.2%) were gang members, and 1408 (25.4%) occurred during drive-by
      shootings. Firearms were used in an increasing proportion of homicides, from
      71.4% in 1979 to 94.5% in 1994. Homicides by semiautomatic handguns dramatically
      increased during the study period. Gang-related homicide rates for African
      American males aged 15 to 19 years increased from 60.50 per 100,000 population
      per year in 1979 to 1981 to 192.41 per 100,000 population per year in 1989 to
      1991. CONCLUSIONS: Gang-related homicides in Los Angeles County have reached
      epidemic proportions and are a major public health problem. To prevent gang
      violence, the root causes of violent street gang formation must be alleviated,
      the cycle of violent street gang involvement must be broken, and access to
      firearms must be limited.

PMID- 7563454
TI  - Hospitalization for congestive heart failure. Explaining racial differences.
AB  - OBJECTIVE: To determine whether the higher rate of hospitalization among African
      Americans for congestive heart failure (CHF) could be explained by racial
      differences in the prevalence of clinical risk factors for CHF. DESIGN:
      Retrospective cohort study. SETTING: A large health maintenance organization
      (HMO). PATIENTS: A sample of 64,877 enrollees (27% African American and 73%
      white) of the Northern California Kaiser Permanente Medical Care Program who took
      at least one multiphasic health checkup (MHC) at or after the age of 40 years and
      were free of CHF at that time. MAIN OUTCOME MEASURES: First hospitalization with
      a principal diagnosis of CHF. RESULTS: Among cohort members younger than 60 years
      at baseline MHC, the age-adjusted risk ratio (RR) (African American/white) for
      CHF hospitalization was 2.14 for men and 2.73 for women, while for persons 60
      years of age and older at MHC, the age-adjusted RR was 1.48 for both sexes. Cox
      proportional hazards models were used to adjust for risk factors and length of
      follow-up. In persons aged 60 years and older, the race difference was explained
      by greater prevalence of hypertension and diabetes in African Americans (RR =
      1.12; 95% confidence interval [CI], 0.94 to 1.34 after adjustment for
      hypertension and diabetes). In those younger than 60 years, findings differed by
      sex. For men, African-American race was no longer a significant predictor of CHF
      after adjusting for hypertension, diabetes, left ventricular hypertrophy on
      electrocardiogram, and body mass index (adjusted RR = 1.16; 95% CI, 0.86 to
      1.56). However, among younger women, African Americans continued at increased
      risk despite adjustment for these variables as well as smoking, plasma
      cholesterol, renal function, alcohol use, and myocardial infarction (adjusted RR
      = 1.49; 95% CI, 1.00 to 2.21). CONCLUSIONS: In this HMO population, the race
      differences in first hospitalization for CHF are largely explained by known
      clinical and behavioral risk factors, although in younger women these risk
      factors do not completely explain the excess risk among African Americans. These
      findings highlight the role of hypertension and diabetes in the development of
      CHF, particularly among African Americans.

PMID- 7563455
TI  - Alcohol interventions in trauma centers. Current practice and future directions.
AB  - Nearly half of all trauma beds are occupied by patients who were injured while
      under the influence of alcohol. Alcoholism plays such a significant role in
      trauma that efforts to reduce injury recurrence are unlikely to be successful if
      it remains untreated. An injury requiring hospitalization creates a unique
      opportunity to intervene and to motivate patients to alter their drinking
      behavior, thereby making trauma centers ideal sites to implement an alcohol
      screening, intervention, and referral program. However, despite emphasis on
      injury control and prevention, little has been done to incorporate alcohol
      intervention programs into care of the injured patient. Effective means of
      intervention exist that are consistent with the time, financial, and staffing
      constraints of trauma centers, and they should be implemented.

PMID- 7563456
TI  - A quantitative assessment of plasma homocysteine as a risk factor for vascular
      disease. Probable benefits of increasing folic acid intakes.
AB  - OBJECTIVES: To determine the risk of elevated total homocysteine (tHcy) levels
      for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic
      acid, and calculate the potential reduction of coronary artery disease (CAD)
      mortality by increasing folic acid intake. DATA SOURCES: MEDLINE search for meta
      analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease
      and 11 studies of folic acid effects on tHcy levels. STUDY SELECTION AND DATA
      EXTRACTION: Studies dealing with CAD, cerebrovascular disease, and peripheral
      arterial vascular disease were selected. Three prospective and six population
      based case-control studies were considered of high quality. Five cross-sectional
      and 13 other case-control studies were also included. Causality of tHcy's role in
      the pathogenesis of vascular disease was inferred because of consistency across
      studies by different investigators using different methods in different
      populations. DATA SYNTHESIS: Elevations in tHcy were considered an independent
      graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR)
      for CAD of a 5-mumol/L tHcy increment is 1.6 (95% confidence interval [CI], 1.4
      to 1.7) for men and 1.8 (95% CI, 1.3 to 1.9) for women. A total of 10% of the
      population's CAD risk appears attributable to tHcy. The OR for cerebrovascular
      disease (5-mumol/L tHcy increment) is 1.5 (95% CI, 1.3 to 1.9). Peripheral
      arterial disease also showed a strong association. Increased folic acid intake
      (approximately 200 micrograms/d) reduces tHcy levels by approximately 4 mumol/L.
      Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect
      of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain
      fortification. Under different assumptions, 13,500 to 50,000 CAD deaths annually
      could be avoided; fortification of food had the largest impact. CONCLUSIONS: A 5
      mumol/L tHcy increment elevates CAD risk by as much as cholesterol increases of
      0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises
      to prevent arteriosclerotic vascular disease. Clinical trials are urgently
      needed. Concerns about masking cobalamin deficiency by folic acid could be
      lessened by adding 1 mg of cobalamin to folic acid supplements.

PMID- 7563458
TI  - Older drivers and physicians.

PMID- 7563457
TI  - ECASS: lessons for future thrombolytic stroke trials. European Cooperative Acute
      Stroke Study.

PMID- 7563459
TI  - The Lasker Awards at fifty.

PMID- 7563460
TI  - The 1995 Albert Lasker Medical Research Award. Helicobacter pylori. The etiologic
      agent for peptic ulcer.

PMID- 7563461
TI  - The 1995 Albert Lasker Medical Research Award. The keys to cell-mediated
      immunity.

PMID- 7563462
TI  - The 1995 Albert Lasker Medical Research Award. MHC-restricted T-cell recognition.
      The basis of immune surveillance.

PMID- 7563463
TI  - The 1995 Albert Lasker Medical Research Award. The concept of antigen processing
      and presentation.

PMID- 7563464
TI  - The 1995 Albert Lasker Medical Research Award. The class I and class II proteins
      of the human major histocompatibility complex.

PMID- 7563465
TI  - The 1995 Albert Lasker Medical Research Award. The war against disease and
      disability.

PMID- 7563466
TI  - Hepatitis B virus vaccination of medical students: a call for rigorous standards.

PMID- 7563467
TI  - A call for health policy education in the medical school curriculum.

PMID- 7563468
TI  - Medical technology watchdog plays unique role in quality assessment.

PMID- 7563469
TI  - A piece of my mind. Ashes, ashes.

PMID- 7563470
TI  - Conference seeks to provide basis for prostate cancer guidance message.

PMID- 7563471
TI  - ERISA ruling creates options for state reforms.

PMID- 7563472
TI  - Elective acquaints medical students with abortion.

PMID- 7563474
TI  - From the Centers for Disease Control and Prevention. Arboviral disease--United
      States, 1994.

PMID- 7563473
TI  - From the Food and Drug Administration.

PMID- 7563475
TI  - From the Centers for Disease Control and Prevention. Disabilities among children
      aged < or = 17 years--United States, 1991-1992.

PMID- 7563476
TI  - From the Centers for Disease Control and Prevention. NIOSH alert: request for
      assistance in preventing deaths and injuries of adolescent workers.

PMID- 7563477
TI  - The future of the Department of Veterans Affairs.

PMID- 7563478
TI  - Antibiotic treatment for exacerbations of chronic obstructive pulmonary disease.

PMID- 7563479
TI  - Exercise intensity and longevity in men.

PMID- 7563480
TI  - Promotion of women physicians in academic medicine.

PMID- 7563481
TI  - Promotion of women physicians in academic medicine.

PMID- 7563482
TI  - Educational attainment in survivors of ALL.

PMID- 7563483
TI  - Controlling costs: the case of Kaiser.

PMID- 7563484
TI  - The relationship between coronary angioplasty procedure volume and major
      complications.
AB  - OBJECTIVE: To assess the relationship between the volume of percutaneous
      transluminal coronary angioplasty (PTCA) procedures performed in a cardiac
      catheterization laboratory and major complications after adjusting for case mix
      and to evaluate the applicability of current guidelines for minimum laboratory
      volume. DESIGN: Cohort study using the 1992 and 1993 registries of the Society
      for Cardiac Angiography and Interventions. SETTING: Forty-eight cardiac
      catheterization laboratories from throughout the United States and Canada.
      PATIENTS: All 19 594 consecutive patients without an acute myocardial infarction
      (MI) undergoing a first coronary balloon angioplasty. MAIN OUTCOME MEASURES:
      Emergency bypass surgery, MI, or in-hospital death. RESULTS: There was a
      significant decrease in the rates of in-hospital mortality (P = .04), emergency
      bypass surgery (P < .001), MI (P - .001), and major complications (defined as one
      or more of these outcomes; P < .001) with increasing cardiac catheterization
      laboratory volume. After adjustment for case mix using multivariable analysis,
      these associations persisted, although the association with mortality was no
      longer statistically significant. There was no significant difference in outcomes
      in laboratories performing at least 200 vs fewer than 200 procedures per year,
      the currently recommended minimum laboratory volume (odds ratio [OR] for major
      complications, 0.81; 95% confidence interval [CI], 0.53 to 1.25). However, a
      statistically significant decrease in major complications was observed in
      laboratories performing more than 400 procedures per year (adjusted OR, 0.66; 95%
      CI, 0.46 to 0.96; P = .03; and OR, 0.54; 95% CI, 0.38 to 0.78; P = .001) when
      laboratories performing 400 through 599 procedures and at least 600 procedures
      per year, respectively, are compared with those performing fewer than 200 per
      year. CONCLUSIONS: An inverse association between cardiac catheterization
      laboratory procedure volume and major complications during PTCA exists
      independent of differences in patients' risk profiles. Our data suggest that the
      currently recommended minimum laboratory volume may be too low to distinguish
      higher-risk from lower-risk laboratories.

PMID- 7563485
TI  - Trends of diarrheal disease--associated mortality in US children, 1968 through
      1991.
AB  - OBJECTIVES: To describe temporal patterns in mortality related to diarrheal
      disease in US children and to assess progress toward its prevention and control.
      DESIGN: Retrospective analyses of death certificate data on diarrhea of all
      causes compiled by the National Center for Health Statistics, Centers for Disease
      Control and Prevention, Atlanta, Ga. PATIENTS: Children aged 1 month through 4
      years who died with diarrhea. SETTING: United States, 1968 through 1991. RESULTS:
      A total of 14 137 deaths associated with diarrhea among children were reported in
      the United States between 1968 and 1991. Of these, 78% occurred in infants (ie,
      aged 1 to 11 months); the median age at the time of death has declined from 5 to
      1.5 months. Diarrheal disease mortality dropped by approximately 75% during the
      first 18 years of the study, but no decline has occurred since 1985. Infant
      mortality due to diarrhea (per 100 000 live births) averaged 12.8 and was found
      to be high for blacks (33.1) and for residents of the southern United States
      (18.5). The infant mortality due to diarrhea from 1986 through 1991 is 5.9. Peaks
      in winter deaths previously associated with rotavirus were prominent in the early
      years among infants aged 4 through 11 months. Such peaks have virtually
      disappeared since 1985. Diarrhea was the principal cause of death, as the leading
      associated diagnoses (electrolyte disorders [30%], cardiac arrest [16%], shock
      [8%], and nausea/vomiting [4%]) were commonly recognized complications of
      diarrhea. Since 1979, prematurity has emerged as a common associated diagnosis.
      CONCLUSIONS: Diarrheal deaths nationwide have declined 75% from 1968 to 1985 but
      stabilized since then at about 300 deaths per year. Because many of these deaths
      may still be preventable by early rehydration, future prevention efforts should
      be directed at educating health care providers about the continuing problem and
      recognition of the high-risk infant and at teaching mothers of such infants to
      begin rehydration early and to seek medical attention when their infant develops
      diarrhea.

PMID- 7563486
TI  - Consequences of direct genetic testing for germline mutations in the clinical
      management of families with multiple endocrine neoplasia, type II.
AB  - OBJECTIVE: Multiple endocrine neoplasia, type II (MEN-II) is an autosomal
      dominant disorder characterized by tumors of thyroid C cells and
      pheochromocytoma. Recently, germline mutations in the RET proto-oncogene have
      been identified in patients with MEN-II. The aims of this study were (1) to
      define the mutations in clinically diagnosed MEN-II families, (2) to compare the
      results of genetic and biochemical testing, and (3) to evaluate the impact of
      mutation analyses for the members of these families. DESIGN: Register-based
      survey study of clinically affected and unaffected members of MEN-II families.
      SETTING: Register of families from Germany and Spain with pheochromocytomas. Two
      research laboratories at Cambridge University in the United Kingdom. PATIENTS: We
      investigated consenting affected and unaffected members belonging to a series of
      10 families who met the clinical criteria for MEN-II. MAIN OUTCOME MEASURES: (1)
      Presence or absence of germline mutation in the RET proto-oncogene in affected
      and unaffected members of the 10 families, and (2) in the absence of RET mutation
      in a given family, presence or absence of germline mutation in the von Hippel
      Lindau (VHL) gene, which is the susceptibility gene involved in a closely related
      syndrome, von Hippel-Lindau disease. RESULTS: In eight of these families, RET
      mutations were identified. The specific mutations were detected in all affected
      members. The remaining two families without RET mutations were subsequently shown
      to have a mutation within the VHL gene. The VHL mutations were identified in both
      families and represent a previously undescribed base change. After identification
      of the mutation, premorbid genetic testing was performed in all MEN-II and VHL
      families, resulting in detection of asymptomatic carriers in the MEN-II families.
      Clinically, the two VHL families differed from the eight MEN-II families by the
      presence of a C-cell tumor in only one individual from each family and extra
      adrenal pheochromocytoma in three of nine affected individuals in the two
      families combined. CONCLUSIONS: The diagnosis of MEN-II should be confirmed by
      molecular genetic analysis and the diagnosis of VHL syndrome should be considered
      for families with an absence of RET mutations and a preponderance of
      pheochromocytomas.

PMID- 7563487
TI  - Treatment of hyperlipidemia in women.
AB  - OBJECTIVE: To assess the evidence that lipid lowering prevents coronary heart
      disease (CHD) events in women. DATA SOURCES: English-language literature
      assessing the effects of cholesterol lowering with dietary and/or drug
      interventions as primary or secondary prevention on CHD events in women. MAIN
      OUTCOME MEASURES: Coronary heart disease and total mortality were the primary
      outcomes assessed. Angiographic regression of coronary atherosclerosis was a
      secondary outcome. STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: All nine
      of the identified studies that met the criteria were included. Relative risks for
      CHD and total mortality were calculated from available data. Summary relative
      risks were calculated using meta-analytic techniques. CONCLUSIONS: There is no
      evidence from primary prevention trials that cholesterol lowering affects total
      mortality in healthy women, although the available data are limited. Limited
      evidence suggests that treatment of hypercholesterolemia in women with coronary
      disease may decrease CHD mortality. Future research should address the role of
      dietary and other nondrug treatment of hypercholesterolemia in women at high risk
      for CHD.

PMID- 7563488
TI  - A couple with infertility.

PMID- 7563490
TI  - The critical question of procedure volume minimums for coronary angioplasty.

PMID- 7563489
TI  - Pediatric HIV disease, zidovudine in pregnancy, and unblinding heelstick surveys.
      Reframing the debate on prenatal HIV testing.

PMID- 7563491
TI  - Forensic scientists helping Haiti heal.

PMID- 7563492
TI  - Other AIDS drug regimens beat AZT alone, reduce clinical progression and
      mortality.

PMID- 7563493
TI  - Informed consent waiver for emergency research.

PMID- 7563494
TI  - From the Health Care Financing Administration.

PMID- 7563495
TI  - From the Centers for Disease Control and Prevention. Human rabies--Washington,
      1995.

PMID- 7563496
TI  - From the Centers for Disease Control and Prevention. Histoplasmosis--Kentucky,
      1995.

PMID- 7563497
TI  - From the Centers for Disease Control and Prevention. Knowledge and use of folic
      acid by women of childbearing age--United States, 1995.

PMID- 7563498
TI  - Idiopathic progressive spastic paraparesis.

PMID- 7563499
TI  - Restless legs syndrome.

PMID- 7563500
TI  - Rotating tourniquets for acute cardiogenic pulmonary edema.

PMID- 7563501
TI  - The role of schools in Healthy People 2000.

PMID- 7563502
TI  - Informed consent for emergency research.

PMID- 7563503
TI  - Colloidal silver proteins marketed as health supplements.

PMID- 7563504
TI  - Fruits, vegetables, and stroke risk.

PMID- 7563506
TI  - Lewy body pathology and heterogeneity of Alzheimer's disease.

PMID- 7563505
TI  - Lipoprotein(a) concentration and risk of atherothrombotic disease.

PMID- 7563507
TI  - Ocular manifestations of Wegener's granulomatosis.

PMID- 7563508
TI  - Attitudes about cancer screening: dinnertime bias.

PMID- 7563509
TI  - Prevention of hepatitis B virus transmission by immunization. An economic
      analysis of current recommendations.
AB  - OBJECTIVE: To evaluate the outcome of immunization strategies to prevent
      hepatitis B virus (HBV) transmission. DESIGN AND SETTING: A decision model was
      used to determine the incremental effects of the following hepatitis B
      immunization strategies in a birth cohort receiving immunization services in the
      public sector: (1) prevention of perinatal HBV infection, (2) routine infant
      vaccination, or (3) routine adolescent vaccination. MAIN OUTCOME MEASURES: Over
      the lifetime of the cohort, the reduction in infections and medical and work-loss
      costs of HBV-related liver disease were determined for each strategy and compared
      with the outcome without immunization. RESULTS: Prevention of perinatal infection
      and routine infant vaccination would lower the 4.8% lifetime risk of HBV
      infection by at least 68%, compared with a 45% reduction for adolescent
      vaccination. From a societal perspective, each strategy was found to be cost
      saving, but was not cost saving with respect to direct medical costs. The
      estimated cost per year of life saved was $164 to prevent perinatal HBV
      infection, $1522 for infant vaccination, and $3730 for adolescent vaccination.
      CONCLUSIONS: Routine vaccination of infants in successive birth cohorts to
      prevent HBV transmission is cost-effective over a wide range of assumptions.
      While economically less attractive than infant vaccination, adolescent
      vaccination could serve to protect those children who were not vaccinated as
      infants.

PMID- 7563510
TI  - Assessment of a universal, school-based hepatitis B vaccination program.
AB  - OBJECTIVE: To assess a hepatitis B vaccination program offered to all grade 6
      students in British Columbia in 1992. DESIGN: Cohort study. SETTING: British
      Columbia, Canada. PARTICIPANTS: All grade 6 students were offered vaccine.
      Subsets of 454 and 259 students participated in studies of minor adverse events
      and seroresponse, respectively. INTERVENTION: The vaccine used was Engerix-B, 20
      micrograms, given at intervals of 0, 1, and 6 months. MAIN OUTCOME MEASURES:
      Province-wide acceptance and series completion rates and reports of severe
      adverse events. Minor adverse events and immunogenicity in subsamples. RESULTS: A
      total of 127,922 vaccine doses were administered. Initial enrollment totaled
      43,358 students or 95.4% of those eligible. The series was completed by 41,594
      students (95.6%). Minor adverse events were infrequent in the cohort assessed: no
      absenteeism or physician visits resulted from vaccination. Sixty-nine reported
      severe adverse events met surveillance definitions, the major categories being
      injection site reactions (23% of reports), fainting (20%), and rashes (17%).
      There was one instance of anaphylaxis. Only 13 of these events resulted in
      recommendations to discontinue the series. Of students tested following the
      series, 98% had levels of antibody to hepatitis B surface antigen considered to
      be protective (> or = 10 IU/L), the geometric mean titer being 690 IU/L (95%
      confidence interval, 498 to 957 IU/L). CONCLUSION: Our experience indicates that
      school-based programs for universal vaccination of preadolescents can be highly
      acceptable and efficient.

PMID- 7563511
TI  - Evaluation of percentage of free serum prostate-specific antigen to improve
      specificity of prostate cancer screening.
AB  - OBJECTIVE: To evaluate measurement of percentage of free prostate-specific
      antigen (PSA) in serum to improve the specificity of prostate cancer screening in
      men with serum PSA levels between 4.1 and 10.0 ng/mL. DESIGN: Retrospective,
      nonrandomized analysis using a research assay for measuring free PSA in frozen
      serum from men with a spectrum of prostate sizes and digital rectal examination
      results. SETTING: General community outpatient prostate cancer screening program
      at a university center. PATIENTS: One hundred thirteen men aged 50 years or
      older, 99% of whom were white, with serum PSA concentrations of 4.1 to 10.0
      ng/mL, including 63 men with histologically confirmed benign prostatic
      hyperplasia, 30 with prostate cancer with an enlarged gland, and 20 with cancer
      with a normal-sized gland. All study volunteers had undergone prostatic
      ultrasonography and biopsy. MAIN OUTCOME MEASURES: Percentage of free PSA in
      serum and percentage of free PSA cutoff that maintained at least 90% sensitivity
      for prostate cancer detection. RESULTS: Median percentage of free PSA was 9.2% in
      men with cancer and a normal-sized gland, 15.9% in men with cancer and an
      enlarged gland, and 18.8% in men with benign prostatic hyperplasia (P < .001).
      The percentage of free PSA cutoff was higher in men with an enlarged gland and in
      those with a palpably benign gland. In men with an enlarged, palpably benign
      gland, a free PSA cutoff of 23.4% or lower detected at least 90% of cancers and
      would have eliminated 31.3% of negative biopsies. CONCLUSIONS: Measurement of
      percentage of free serum PSA improves specificity of prostate cancer screening in
      selected men with elevated total serum PSA levels and can reduce unnecessary
      prostate biopsies with minimal effects on the cancer detection rate; however,
      further studies are needed to define optimal cutoffs. Final evaluation of PSA
      screening also must consider the ability of current treatments to improve the
      prognosis of screen-detected prostate cancer.

PMID- 7563512
TI  - The role of polyneuropathy in motor convalescence after prolonged mechanical
      ventilation.
AB  - OBJECTIVE: To test the hypothesis that prolonged motor recovery after long-term
      ventilation may be due to polyneuropathy and can be foreseen at an early stage by
      electromyography (EMG). DESIGN: Cohort study with an entry period of 18 months.
      Polyneuropathy was identified by EMG studies in the intensive care unit (ICU).
      During a 1-year follow-up, amount of time was recorded to reach a rehabilitation
      end point. SETTING: The general ICU of a community hospital. PATIENTS: Fifty
      patients younger than 75 years who were receiving mechanical ventilation for more
      than 7 days. MAIN OUTCOME MEASURES: A rehabilitation end point was defined as
      return of normal muscle strength and ability to walk 50 m independently. RESULTS:
      In 29 of 50 patients, an EMG diagnosis of polyneuropathy was made in the ICU.
      Patients with polyneuropathy had a higher mortality in the ICU (14 vs 4; P =
      .03), probably related to multiple organ failure (22 vs 11; P = .08) or
      aminoglycoside treatment of suspected gram-negative sepsis (17 vs 4; P = .05).
      Rehabilitation was more prolonged in 12 patients with polyneuropathy than in 12
      without polyneuropathy (P = .001). Of nine patients with delays beyond 4 weeks,
      eight had polyneuropathy, five of whom had persistent motor handicap after 1
      year. In particular, axonal polyneuropathy with conduction slowing on EMG
      indicated a poor prognosis. CONCLUSIONS: Polyneuropathy in the critically ill is
      related to multiple organ failure and gram-negative sepsis, is associated with
      higher mortality, and causes important rehabilitation problems. EMG recordings in
      the ICU can identify patients at risk.

PMID- 7563513
TI  - Maintaining low HIV seroprevalence in populations of injecting drug users.
AB  - OBJECTIVES: To describe prevention activities and risk behavior in cities where
      human immunodeficiency virus (HIV) was introduced into the local population of
      injecting drug users (IDUs), but where seroprevalence has nevertheless remained
      low (< 5%) during at least 5 years. DESIGN AND SETTING: A literature search
      identified five such cities: Glasgow, Scotland; Lund, Sweden; Sydney, New South
      Wales, Australia; Tacoma, Wash; and Toronto, Ontario. Case histories were
      prepared for each city, including data on prevention activities and current
      levels of risk behavior among IDUs. PARTICIPANTS: Injecting drug users recruited
      from both drug treatment and non-treatment settings in each city. INTERVENTIONS:
      A variety of HIV prevention activities for IDUs had been implemented in each of
      the five cities. RESULTS: There were three common prevention components present
      in all five cities: (1) implementation of prevention activities when HIV
      seroprevalence was still low, (2) provision of sterile injection equipment, and
      (3) community outreach to IDUs. Moderate levels of risk behavior continued with
      one third or more of the IDUs reporting recent unsafe injections. CONCLUSIONS: In
      low-seroprevalence areas, it appears possible to severely limit transmission of
      HIV among populations of IDUs, despite continuing risk behavior among a
      substantial proportion of the population. Pending further studies, the common
      prevention components (beginning early, community outreach, and access to sterile
      injection equipment) should be implemented wherever populations of IDUs are at
      risk for rapid spread of HIV.

PMID- 7563514
TI  - Cigarette smoking in China. Prevalence, characteristics, and attitudes in Minhang
      District.
AB  - OBJECTIVE: To determine the prevalence, pattern, and financial implications of
      cigarette smoking and the attitudes toward and knowledge of the health effects of
      tobacco use in a population in China. DESIGN: A two-stage, stratified cluster
      survey using door-to-door interviews. SETTING: Minhang District, China (near
      Shanghai), with a population of 506,000. PARTICIPANTS: A total of 3423 males and
      3593 females aged 15 years and older. MAIN OUTCOME MEASURES: Smoking prevalence,
      age of initiation of smoking, reasons for smoking, knowledge of tobacco hazards,
      and costs of smoking. RESULTS: A total of 2279 males (67%) but only 72 females
      (2%) smoke. Many males initiate smoking in adulthood. A total of 1156 males
      (50.7%) began smoking between 20 and 24 years of age, and 666 (29.2%) began
      between 25 and 39 years of age. Among all respondents, 6202 (88.4%) believe
      smoking is harmful for both the smoker and those exposed passively to the smoke.
      Only 332 (14.1%) of all male smokers reported a desire to quit smoking. Current
      smokers spent an average of 3.65 yuan daily on cigarettes or 1332 yuan yearly
      (8.5 yuan per US dollar), which represents 60% of personal income and 17% of
      household income. CONCLUSIONS: The survey reveals a dangerous health situation
      that in all likelihood will worsen. More than two thirds of men smoke, and people
      in successive age cohorts start smoking at earlier ages. Smokers spend a
      substantial proportion of their income on cigarettes. There is a low rate of
      quitting and a low desire to quit despite high awareness of the health hazards.
      Tobacco control measures need to be implemented urgently in China.

PMID- 7563516
TI  - The public's health unprotected. Reversing a decade of underutilization of
      hepatitis B vaccine.

PMID- 7563515
TI  - TennCare--health system reform for Tennessee.
AB  - TennCare, the health care system reform plan implemented in Tennessee on January
      1, 1994, was developed with the dual objectives of controlling the rapidly rising
      cost of the state's Medicaid program and extending health insurance coverage to
      most Tennesseans without access to employer-sponsored or other government
      sponsored health insurance. Beneficiaries enroll in competing, state-chartered
      managed care organizations that are responsible for providing broad preventive,
      inpatient, and outpatient services and are reimbursed by the state on a
      capitation basis at a rate based on a statewide global budget for health care.
      The program initially proposed to enroll up to 1,775,000 citizens and was
      projected to result in a cumulative cost savings to Tennessee and the federal
      government of $7.2 billion by the end of the 5-year demonstration period.
      However, major start-up problems encountered by the state and by managed care
      organizations and limitations imposed by the government have significantly
      constrained these expectations. At the end of its first year, more than 1.2
      million citizens were enrolled, but the program incurred a $99 million deficit.
      Managed care organizations and hospitals have reported major financial problems,
      and constituency groups--especially those representing physicians--have attempted
      to block the program. Our objective is to describe the design and rationale of
      TennCare and discuss key issues the plan continues to face that may affect its
      long-term success.

PMID- 7563517
TI  - New initiative for global TB control.

PMID- 7563519
TI  - From the Centers for Disease Control and Prevention. Syringe exchange programs-
      United States, 1994-1995.

PMID- 7563520
TI  - From the Centers for Disease Control and Prevention. State and national
      vaccination coverage levels among children aged 19-35 months--United States,
      April-December 1994.

PMID- 7563518
TI  - Research priorities for Parkinson's recommended.

PMID- 7563522
TI  - Menopause in Japanese women.

PMID- 7563521
TI  - From the Centers for Disease Control and Prevention. Blood lead levels among
      children in a managed-care organization--California, October 1992-March 1993.

PMID- 7563523
TI  - The patient-physician covenant.

PMID- 7563524
TI  - Ischemic stroke and activated protein C resistance.

PMID- 7563525
TI  - Losartan and severe migraine.

PMID- 7563526
TI  - Physicians and pharmaceutical sales representatives.

PMID- 7563527
TI  - Physicians and pharmaceutical sales representatives.

PMID- 7563528
TI  - The 'nursing' in nursing homes.

PMID- 7563529
TI  - Talc and condoms.

PMID- 7563530
TI  - HIV prevention: community planning groups.

PMID- 7563531
TI  - A randomized controlled trial of an HIV sexual risk-reduction intervention for
      young African-American women.
AB  - OBJECTIVE: To evaluate the efficacy of a community-based social skills human
      immunodeficiency virus (HIV) prevention intervention to enhance consistent condom
      use. DESIGN: A randomized, single-blind controlled trial. SETTING: Bayview
      Hunter's Point neighborhood of San Francisco, Calif, a predominantly African
      American community that is economically disadvantaged. PARTICIPANTS: A sample of
      128 sexually active, heterosexual, African-American women 18 through 29 years of
      age was recruited using street outreach techniques. Participants completed a
      structured baseline interview; 100 women (78.1%) completed 3-month follow-up
      interviews. INTERVENTION: Women randomized to the social skills intervention
      completed five sessions that emphasized ethnic and gender pride, HIV risk
      reduction information, sexual self-control, sexual assertiveness and
      communication skills, proper condom use skills, and developing partner norms
      supportive of consistent condom use. Women randomized to the HIV education
      condition participated in a single session that provided HIV risk-reduction
      information. Women randomized to the delayed HIV education control condition
      received no HIV risk-reduction information until all follow-up interviews were
      completed. MAIN OUTCOME MEASURES: Consistent condom use, HIV risk-reduction
      knowledge, sexual self-control, sexual assertiveness, sexual communication, and
      partner norms supportive of consistent condom use. RESULTS: Compared with the
      delayed HIV education control condition, women in the social skills intervention
      demonstrated increased consistent condom use (adjusted odds ratio [OR], 2.1; 95%
      confidence interval [CI], 1.03 to 4.15; P = .04), greater sexual self-control
      (adjusted OR, 1.9; 95% CI, 1.00 to 3.60; P = .05), greater sexual communication
      (adjusted OR, 4.1; 95% CI, 1.67 to 10.01; P = .002), greater sexual assertiveness
      (adjusted OR, 1.8; 95% CI, 1.01 to 3.27; P = .05), and increased partners'
      adoption of norms supporting consistent condom use (adjusted OR, 2.1; 95% CI,
      1.08 to 3.87; P = .03). No statistically significant differences in outcome
      variables were observed between the HIV education condition relative to the
      delayed HIV education control condition. CONCLUSION: Community-based HIV risk
      reduction programs that are gender relevant and culturally sensitive and provide
      social skills training can effectively enhance consistent condom use.

PMID- 7563532
TI  - Prostate-specific antigen values at the time of prostate cancer diagnosis in
      African-American men.
AB  - OBJECTIVE: To determine if African-American men with newly diagnosed prostate
      cancer (PC) have higher pretreatment serum prostate-specific antigen (PSA) values
      after adjustment for clinical stage, age, and tumor grade, and to determine if
      any difference detected is related to tumor volume difference. DESIGN:
      Consecutive case series of newly diagnosed PC patients between January 1990 and
      September 1994 and cohort analytic study of PC patients treated by radical
      prostatectomy (RP) and who had whole-mount pathologic tumor volume assessment
      between May 1993 December 1994. SETTING: Tertiary care military medical center.
      PATIENTS: A total of 541 evaluable newly diagnosed PC patients (408 white and 133
      black) having pretreatment PSA assessment at one laboratory; 91 patients
      undergoing RP had whole-mount tumor volume analysis. INTERVENTIONS: Medical
      record review for pretreatment PSA value, race, tumor grade, clinical stage, and
      age, as well as whole-mount pathologic assessment of RP specimen and measurement
      of tumor volume. MAIN OUTCOME MEASURES: The PSA differences between black and
      white PC patients with adjustments for age, biopsy tumor grade (Gleason score),
      and clinical stage (TNM stage); PSA differences between black and white PC
      patients undergoing RP with adjustment for age, RP grade, clinical stage, and
      tumor volume. RESULTS: The mean (geometric) PSA value for 133 black men was 14.00
      ng/mL compared with 8.29 ng/mL for 408 white men (P < .001). The black patients
      had higher PSA values across all stage, grade, and age categories. The racial
      difference in PSA levels remained statistically significant when stage, grade,
      and age were simultaneously controlled for (P < .001). Multivariable odds ratio
      testing revealed that even after adjustment for stage, grade, and age, black
      patients were 2.2 times as likely as white patients to have a PSA value greater
      than 10.0 ng/mL (95% confidence interval, 1.3 to 3.6). Tumor volume (geometric
      mean) was 5.42 cm3 and 2.10 cm3 for black and white RP patients, respectively (P
      = .002). Across all clinical stages (T1a to T3), black men had tumor volumes 1.3
      to 2.5 times greater than those of white men. Multivariable analysis of
      covariance revealed that tumor volume and stage of disease were important
      predictors of PSA level, but race, grade, and age were not. (The percentage of
      white and black patients whose cancer was detected by screening [75.4% vs 70.4%]
      or who had symptoms [37.7% vs 29.6%] was not significantly different.)
      CONCLUSIONS: As a group, African-American men with newly diagnosed PC have higher
      PSA values at initial diagnosis than white men. This PSA difference appears to be
      due to larger tumor volumes within clinical (TNM) stage categories among black
      patients. Elevated PSA value was a surrogate for larger tumor volume in this
      cohort of black men. This stage-for-stage tumor volume disparity even in an equal
      access health care environment should prompt further study of screening behavior
      and/or biological differences of PC in the black population.

PMID- 7563533
TI  - Regionalization of cardiac surgery in the United States and Canada. Geographic
      access, choice, and outcomes.
AB  - OBJECTIVE: To determine how regionalization of facilities for coronary artery
      bypass surgery (CABS) affects geographic access to CABS and surgical outcomes.
      DESIGN: Computerized hospital discharge records were used to measure hospital
      CABS volume and in-hospital post-CABS mortality rates. Relationships between
      surgical volume and age- and sex-adjusted mortality rates were compared using chi
      2 tests. Small-area analysis of the association between CABS rates and distances
      to nearest CABS hospital was performed using multivariate linear regression
      methods. SETTING: All nonfederal hospitals in New York, California, Ontario,
      Manitoba, and British Columbia. PATIENTS: All adult residents of the five
      jurisdictions who underwent CABS in a hospital in their jurisdiction from 1987
      through 1989. RESULTS: In New York and Canada, approximately 60% of all CABS
      operations took place in hospitals performing 500 or more CABS operations per
      year, compared with only 26% in California. The highest mortality rates were
      found among California hospitals performing fewer than 100 CABS operations per
      year (adjusted 14-day in-hospital mortality was 4.7% compared with 2.4% in high
      volume California hospitals, P < .001). The percentage of the population residing
      within 25 miles of a CABS hospital was 91% in California, 82% in New York, and
      less than 60% in Canada. Eliminating very low-volume (< 100 cases per year) CABS
      hospitals in California would increase travel distances to a CABS hospital only
      slightly for a small number of residents. The Canadian degree of regionalization
      was not associated with lower CABS rates within provinces for populations living
      at more remote distances from the nearest CABS hospital. CONCLUSION:
      Regionalization of CABS facilities in New York and Canada largely avoids the
      problem of low-volume outlier hospitals with high postoperative mortality rates
      found in California. New York has avoided the redundancy of facilities that
      exists in California while still providing residents a geographically convenient
      selection of CABS hospitals. Stricter regionalization in Canada may leave
      residents with a more narrow choice of facilities, but does not
      disproportionately affect access to surgery for populations living at remote
      distances from CABS facilities.

PMID- 7563534
TI  - Multiple organ dysfunction syndrome in bone marrow transplantation.
AB  - OBJECTIVE: To define the frequency and outcome of organ dysfunction in bone
      marrow transplantation (BMT) and to determine if patients with organ dysfunction
      have lower levels of protein C (PC) and/or antithrombin III (ATIII) than those
      without organ dysfunction. DESIGN: Inception cohort of patients undergoing BMT,
      followed for 28 days, until hospital dismissal, or until death. SETTING: Bone
      marrow transplant department of a university hospital. PATIENTS: A total of 199
      consecutive patients admitted for BMT. INTERVENTIONS: Standard supportive care
      was given to all patients. MAIN OUTCOME MEASURES: Definitions of organ
      dysfunction were arrived at prior to beginning the study. They include pulmonary,
      central nervous system (CNS), hepatic, and renal dysfunction. Protein C and ATIII
      levels were measured prior to beginning the preparative regimen and weekly
      thereafter. RESULTS: Single organ dysfunction, manifesting as pulmonary, CNS, or
      hepatic dysfunction, occurred in 93 (48.5%) of the 199 patients and was a strong
      predictor of multiple organ dysfunction syndrome (MODS) and death. Death occurred
      in 14 (7.0%) of the patients. Cause of death was precisely identified in only
      four patients. Low levels of either PC or ATIII were associated with death and
      pulmonary, CNS, and hepatic dysfunction. Multivariate analysis showed ATIII and
      PC levels were associated with single organ dysfunction independent of the type
      of transplant, the type of preparative regimen, and the presence of bacteremia.
      CONCLUSIONS: Single organ dysfunction during BMT is a marker for a systemic
      abnormality that has a high likelihood of progressing to MODS, similar to that
      seen in other critically ill patient populations. MODS is the leading cause of
      death in series of BMT patients. Low levels of ATIII and PC are markers of and
      may be involved in the pathogenesis of MODS in BMT.

PMID- 7563535
TI  - The superficial femoral vein. A potentially lethal misnomer.
AB  - OBJECTIVE: To assess the potential for error in interpretation of venous duplex
      reports that use the term "superficial femoral vein." DESIGN: Three surveys
      conducted by mail. SETTING: Three multispecialty medical groups, anatomy
      departments of all US medical schools, and vascular laboratories. PARTICIPANTS: A
      total of 46 family practitioners and general internists, 95 chairpersons of
      departments of anatomy, and 85 laboratory directors. MAIN OUTCOME MEASURES:
      Proposed treatment of a patient with leg pain and an acute thrombosis of the
      superficial femoral vein; what nomenclature(s) for the deep thigh veins is (are)
      felt to be correct, what are acceptable alternatives, what is taught to students
      and which is preferred; and what terminology is being used in lower limb venous
      duplex reports. RESULTS: Only 24% (11/46) of the respondents would have
      administered anticoagulants to the patient as described. Only 3% (3/95) of
      anatomists felt the term "superficial femoral vein" was correct, 22% (21/95) felt
      it was an acceptable alternative (though only 9% [9/95] taught it to medical
      students), and only 7% (7/95) of anatomists felt the term was preferred for
      everyday use. The term "superficial femoral vein" is used by 93% (79/85) of
      vascular laboratories in lower limb venous duplex reports. CONCLUSION: Although
      the overwhelming majority of vascular laboratories use the term "superficial
      femoral vein" in venous duplex reports, the use of this term is potentially
      hazardous to patients. Most primary care physicians have not been taught and are
      not aware that the superficial femoral vein is a deep vein and that acute
      thrombosis of this vessel is potentially life threatening.

PMID- 7563536
TI  - The rational clinical examination. Is listening for abdominal bruits useful in
      the evaluation of hypertension?

PMID- 7563537
TI  - New estimates of the underinsured younger than 65 years.
AB  - We estimate that at least 29 million Americans with private insurance are
      underinsured. That figure identifies the underinsured younger than 65 years by
      the risk of large out-of-pocket expenditures for an unusually expensive,
      catastrophic illness. A slightly smaller number, about 25 million, are
      underinsured by an alternate definition: they have insurance that pays a smaller
      proportion of claims than the plan with the largest enrollment in the federal
      employee program. The federal employee plan was the insurance standard proposed
      in several recent health system reform bills. Our estimate of the number of
      people who are underinsured for catastrophic illness is almost half again larger
      than the number that was widely cited during last year's debates on health system
      reform. That estimate was based on the same concept but was projected from a
      study published 10 years ago.

PMID- 7563538
TI  - On federal regulation of methadone treatment.

PMID- 7563539
TI  - Opportunities and challenges of laboratory testing at alternative sites.

PMID- 7563540
TI  - Managed care in JAMA and the Archives journals. A call for papers for coordinated
      theme issues.

PMID- 7563542
TI  - Conjugate vaccines hold hope for countering resistant pneumococcus.

PMID- 7563541
TI  - What do Hillary Rodham Clinton and Newt Gingrich have in common?
AB  - In a somewhat tongue-in-cheek style, this article tries to persuade conservatives
      that it might be in their best interests to consider broader health system reform
      alternatives in their quest to reduce the cost of federal health entitlements for
      a balanced budget by 2002. The conventional means for reducing the federal budget
      by $450 billion in 7 years will inflict much pain on many voters. The
      substitution of a new, more targeted entitlement, prospectively, for all
      Americans represents an alternative that provides much gain to many and only some
      pain to a few.

PMID- 7563543
TI  - Learning how phytochemicals help fight disease.

PMID- 7563545
TI  - From the Centers for Disease Control and Prevention. Increasing pneumococcal
      vaccination rates among patients of a national health-care alliance--United
      States, 1993.

PMID- 7563546
TI  - From the Centers for Disease Control and Prevention. Progress toward elimination
      of Haemophilus influenzae type b disease among infants and children--United
      States, 1993-1994.

PMID- 7563547
TI  - From the Centers for Disease Control and Prevention. Increasing influenza
      vaccination rates for Medicare beneficiaries--Montana and Wyoming, 1994.

PMID- 7563544
TI  - From the Institute of Medicine.

PMID- 7563548
TI  - Three vs 10 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis.

PMID- 7563549
TI  - Three vs 10 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis.

PMID- 7563550
TI  - Three vs 10 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis.

PMID- 7563551
TI  - Reporting randomized controlled trials.

PMID- 7563552
TI  - Measuring blood pressure: which arm?

PMID- 7563553
TI  - Cardiac troponin T and point-of-care testing for myocardial infarction.

PMID- 7563554
TI  - Contempo: ethical issues of human embryos research and physician-assisted
      suicide.

PMID- 7563555
TI  - Contempo: ethical issues of human embryos research and physician-assisted
      suicide.

PMID- 7563556
TI  - Boundaries in the physician-patient relationship.

PMID- 7563557
TI  - Boundaries in the physician-patient relationship.

PMID- 7563558
TI  - Varying nicotine patch dose and type of smoking cessation counseling.
AB  - OBJECTIVE: To compare the efficacy and safety of 22-mg and 44-mg doses of
      transdermal nicotine therapy when it is paired with minimal, individual, or group
      counseling to improve smoking cessation rates. DESIGN: An 8-week clinical trial
      (4 weeks double-blind followed by 4 weeks open label) using random assignment of
      participants to both dose (22 or 44 mg) and counseling (minimal, individual, or
      group) conditions. PARTICIPANTS: Daily cigarette smokers (> or = 15 cigarettes
      per day for at least 1 year) who volunteered to participate in a study of smoking
      cessation treatment. A total of 504 participants were enrolled at two sites.
      INTERVENTION: Four weeks of 22- or 44-mg transdermal nicotine therapy followed by
      4 weeks of dosage reduction (2 weeks of 22 mg followed by 2 weeks of 11 mg).
      Counseling consisted of a self-help pamphlet (minimal); a self-help pamphlet, a
      brief physician motivational message, and three brief (< 15 minutes) follow-up
      visits with a nurse (individual); or the pamphlet, the motivational message, and
      eight weekly 1-hour group smoking cessation counseling visits (group). All
      participants returned weekly to turn in questionnaires and for assessment of
      their smoking status. MAIN OUTCOME MEASURES: Abstinence from smoking was based on
      self-report, confirmed by an expired carbon monoxide concentration lower than 10
      ppm. Withdrawal severity was assessed by means of an eight-item self-report
      questionnaire completed daily. RESULTS: Smoking cessation rates for the two
      nicotine patch doses and three levels of counseling did not differ significantly
      at either 8 weeks or 26 weeks following the quit date. Among those receiving
      minimal contact, the 44-mg dose produced greater abstinence at 4 weeks than did
      the 22-mg dose (68% vs 45%; P < .01). Participants receiving minimal-contact
      adjuvant treatment were less likely to be abstinent at the end of 4 weeks than
      those receiving individual or group counseling (56% vs 67%; P < .05). The 44-mg
      dose decreased desire to smoke more than the 22-mg dose, but this effect was not
      related to success in quitting smoking. Transdermal nicotine therapy at doses of
      44 mg produced a significantly greater frequency of nausea (28%), vomiting (10%),
      and erythema with edema at the patch site (30%) than did a 22-mg dose (10%, 2%,
      and 13%, respectively; P < .01 for each adverse effect). Three serious adverse
      events occurred during use of the 44-mg patch dose. CONCLUSIONS: There does not
      appear to be any general, sustained benefit of initiating transdermal nicotine
      therapy with a 44-mg patch dose or of providing intense adjuvant smoking
      cessation treatment. The two doses and all adjuvant treatments produced
      equivalent effects at the 26-week follow-up, and the higher patch dose produced
      more adverse effects. Higher-dose (44-mg) nicotine replacement does not appear to
      be indicated for general clinical populations, although it may provide short-term
      benefit to some smokers attempting to quit with minimal adjuvant treatment.

PMID- 7563559
TI  - High-dose nicotine patch therapy. Percentage of replacement and smoking
      cessation.
AB  - OBJECTIVE: To assess the level of nicotine replacement, evidence of nicotine
      toxicity, and withdrawal symptom relief with placebo and 11-, 22-, and 44-mg/d
      doses of transdermal nicotine. A secondary objective was to assess short- and
      long-term smoking cessation rates. DESIGN: Randomized, double-blind, placebo
      controlled inpatient/outpatient trial. SUBJECTS: Seventy-one cigarette smokers
      stratified according to light (n = 23), moderate (n = 24), and heavy (n = 24)
      smoking rates. INTERVENTIONS: After baseline measures were obtained, subjects
      were randomly assigned to placebo or an 11-, 22-, or 44-mg/d dose of transdermal
      nicotine and admitted to a special hospital unit for intensive inpatient
      treatment of nicotine dependence. During the 6-day inpatient stay, daily nicotine
      and cotinine levels were determined from trough and peak blood samples.
      Outpatient patch therapy continued for 7 weeks following the hospital stay, and
      those initially assigned to placebo were randomly assigned to 11 or 22 mg/d. At
      week 4, the dosage of those initially assigned to 44 mg/d was reduced to 22 mg/d.
      MAIN OUTCOME MEASURES: Percentage of replacement of cotinine was calculated by
      dividing the steady-state levels attained during patch therapy by the
      corresponding baseline levels. Abstinence from smoking was verified by expired
      air carbon monoxide. Withdrawal symptoms and nicotine toxicity were assessed
      daily through questionnaires during the inpatient stay. Follow-up visits were at
      3, 6, 9, and 12 months. RESULTS: There was a statistically significant
      relationship between baseline smoking rate and baseline trough and peak blood
      cotinine levels (rs = 0.39, rs = 0.45; P < .001 in both instances). A dose
      response relationship was observed with higher patch doses, which produced a
      higher percentage of cotinine replacement and better withdrawal symptom relief.
      Only one subject (a light smoker assigned to the 44-mg dose) developed signs of
      nicotine toxicity. There was a positive association between the week 2 patch dose
      and the biochemically confirmed abstinence at the end of patch therapy (P = .007)
      but not for subsequent follow-up times. A higher percentage of cotinine
      replacement was associated with the higher 8-week smoking abstinence rate (P =
      .03), an association not found at long-term follow-up. CONCLUSION: A 44-mg/d dose
      of nicotine patch therapy appears to be safe for use in heavy smokers. Cigarette
      smoking rates can be used to estimate the initial nicotine patch dose. Monitoring
      blood cotinine levels at baseline and steady state can be used for assessing the
      adequacy of nicotine replacement. Withdrawal symptom relief can be improved with
      more complete nicotine replacement. Achieving a greater percentage of nicotine
      replacement may increase the efficacy of nicotine patch therapy.

PMID- 7563560
TI  - The risk of esophageal cancer in patients with achalasia. A population-based
      study.
AB  - OBJECTIVE: To determine more precise and accurate cancer risk estimates for
      achalasia that could be used to plan surveillance. DESIGN: Cohort. SETTING:
      Swedish population. PARTICIPANTS: All patients with achalasia listed in the
      population-based Swedish Inpatient Register from 1964 through 1989. MAIN OUTCOME
      MEASURES: The observed number of cancers in the cohort was compared with expected
      numbers of cancers (standardized incidence ratio [SIR]) for each 5-year age group
      and calendar year of observation, calculated using data from the Swedish Cancer
      Registry. RESULTS: A total of 1062 patients with achalasia accumulated 9864 years
      of follow-up. The mean age at entry was 57.2 years, and the mean age at cancer
      diagnosis was 71.0 years. Esophageal cancer occurred in 24 patients. The risk of
      esophageal cancer in the first year after achalasia diagnosis was extremely high
      (SIR, 126.3; 95% confidence interval [CI], 63.0 to 226.1) as a consequence of
      prevalent cancers leading to distal esophageal obstruction simulating achalasia.
      During years 1 to 24, the risk was increased more than 16-fold (SIR, 16.6; 95%
      CI, 8.8 to 28.3). Annual surveillance after the first year would require 406
      endoscopic examinations in men and 2220 in women to detect one cancer.
      CONCLUSIONS: Patients with achalasia are at markedly increased risk of developing
      esophageal cancer. A substantial number of surveillance examinations might be
      required to screen for cancers, especially in women. It is not known whether
      surveillance will result in improved survival.

PMID- 7563562
TI  - Safety of the blood supply.

PMID- 7563561
TI  - Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty
      acids and the risk of primary cardiac arrest.
AB  - OBJECTIVE: To assess whether the dietary intake of long-chain n-3 polyunsaturated
      fatty acids from seafood, assessed both directly and indirectly through a
      biomarker, is associated with a reduced risk of primary cardiac arrest. DESIGN:
      Population-based case-control study. SETTING: Seattle and suburban King County,
      Washington. PARTICIPANTS: A total of 334 case patients with primary cardiac
      arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493
      population-based control cases and controls, matched for age and sex, randomly
      identified from the community. All cases and controls were free of prior clinical
      heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF
      EXPOSURE: Spouses of case patients and control subjects were interviewed to
      quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the
      prior month and other clinical characteristics. Blood specimens from 82 cases
      (collected in the field) and 108 controls were analyzed to determine red blood
      cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated
      fatty acid intake. RESULTS: Compared with no dietary intake of eicosapentaenoic
      acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3
      fatty acids per month (the mean of the third quartile and the equivalent of one
      fatty fish meal per week) was associated with a 50% reduction in the risk of
      primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4
      to 0.8), after adjustment for potential confounding factors. Compared with a red
      blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty
      acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated
      fatty acid level of 5.0% of total fatty acids (the mean of the third quartile)
      was associated with a 70% reduction in the risk of primary cardiac arrest (OR,
      0.3; 95% CI, 0.2 to 0.6). CONCLUSION: Dietary intake of n-3 polyunsaturated fatty
      acids from seafood is associated with a reduced risk of primary cardiac arrest.

PMID- 7563563
TI  - Infectious disease testing for blood transfusions. NIH Consensus Development
      Panel on Infectious Disease Testing for Blood Transfusions.
AB  - OBJECTIVE: To provide physicians and other transfusion medicine professionals
      with a current consensus on infectious disease testing for blood transfusions.
      PARTICIPANTS: A nonfederal, nonadvocate, 12-member consensus panel representing
      the fields of hematology, infectious disease, transfusion medicine, epidemiology,
      and biostatistics and a public representative. In addition, 23 experts in
      hematology, cardiology, transfusion medicine, infectious disease, and
      epidemiology presented data to the consensus panel and a conference audience of
      450. EVIDENCE: The literature was searched through MEDLINE and an extensive
      bibliography of references was provided to the panel and the conference audience.
      Experts prepared abstracts with relevant citations from the literature.
      Scientific evidence was given precedence over clinical anecdotal experience.
      CONSENSUS: The panel, answering predefined consensus questions, developed their
      conclusions based on the scientific evidence presented in open forum and the
      scientific literature. CONSENSUS STATEMENT: The panel composed a draft statement
      that was read in its entirety and circulated to the experts and the audience for
      comment. Thereafter, the panel resolved conflicting recommendations and released
      a revised statement at the end of the conference. The panel finalized the
      revisions within a few weeks after the conference. CONCLUSIONS: The serum alanine
      aminotransferase test should be discontinued as a surrogate marker for blood
      donors likely to transmit posttransfusion non-A, non-B hepatitis infection since
      specific hepatitis C antibody testing has eliminated more than 85% of these
      cases. Antibody to hepatitis B core antigen testing should continue as it may
      prevent some cases of posttransfusion hepatitis B; it may also act as a surrogate
      marker for human immunodeficiency virus (HIV) infection in donors and may prevent
      a small number of cases of transfusion-transmitted HIV infection. Syphilis
      testing should continue until adequate data can determine its effect on the
      rarity of transfusion-transmitted syphilis. Vigilant public health surveillance
      is critical in responding to emerging infectious disease threats to the blood
      supply.

PMID- 7563564
TI  - Ability of primary care physicians to recognize physical findings associated with
      HIV infection.
AB  - OBJECTIVE: To assess the ability of primary care physicians to identify physical
      findings associated with human immunodeficiency virus (HIV) infection. DESIGN:
      Standardized patient examination. PARTICIPANTS: A total of 134 general internists
      and family practitioners were randomly selected after stratifying by year of
      medical school graduation, specialty, and experience caring for patients with HIV
      infection. MAIN OUTCOME MEASURES: Recognition of physical findings of Kaposi's
      sarcoma, oral hairy leukoplakia, and diffuse lymphadenopathy. RESULTS: Despite
      being directed by presenting histories to sites of prominent physical
      abnormalities, only 23 (25.8%) of 89 physicians evaluating a patient with
      Kaposi's sarcoma and 22 (22.7%) of 97 physicians evaluating a patient with oral
      hairy leukoplakia detected and correctly diagnosed the abnormalities. Twenty
      three (17%) of 133 physicians detected diffuse lymphadenopathy in a patient
      complaining of fatigue, fever, and arthralgias. Physicians with the most
      experience treating patients with HIV infection more frequently identified oral
      hairy leukoplakia, but HIV experience did not influence identification of
      Kaposi's sarcoma or detection of lymphadenopathy. There were no differences
      between general internists and family practitioners or among physicians by year
      of medical school graduation in identifying the three physical findings
      associated with HIV infection. CONCLUSIONS: Primary care physicians may
      frequently miss important physical findings related to HIV infection during
      patient examinations.

PMID- 7563566
TI  - Treatment of nicotine dependence. Is more better?

PMID- 7563565
TI  - A 79-year-old musician with asymptomatic carotid artery disease.

PMID- 7563568
TI  - My secret.

PMID- 7563567
TI  - Assisting troubled medical students.

PMID- 7563569
TI  - Counseling services at the University of California, Davis: helping medical
      students cope.
AB  - Our on-site counseling for medical students at UCD School of Medicine has
      provided easily accessible services by psychologists who understand the rules,
      values, and traditions of the medical training experience. We also have had the
      benefit of a close working relationship with the faculty, staff, and
      administration of the School of Medicine. Counseling can facilitate exploration
      of personal issues that have been exposed during medical training, and it offers
      medical students an opportunity to learn new coping skills and enhance their
      understanding of themselves and their training environment, which in turn
      contributes to their professional growth. On-site psychological services also
      provide faculty and staff with a referral resource when they encounter students
      who present with specific psychological challenges and concerns. We encourage
      students who are experiencing the stress of their arduous training experience to
      seek counseling when their usual coping strategies are exhausted. We encourage
      other medical schools to provide effective, accessible counseling services to
      their students. These services will assist in the development of a training
      atmosphere in which students can learn that medical education involves their
      whole person.

PMID- 7563570
TI  - Students' use of psychiatric services: the Columbia experience.
AB  - Medical students spend almost a decade learning how to take good care of their
      patients. No less time and effort should be spent in learning how to take good
      care of themselves. When students find themselves needing assistance in sorting
      out their problems, we are available to help them conceptualize their
      difficulties and carry out an appropriate treatment regimen in a fully
      confidential matter.

PMID- 7563571
TI  - A piece of my mind. Respect for the dead.

PMID- 7563572
TI  - Haemorrheologic and haemostatic factors in ischaemic heart disease.

PMID- 7563573
TI  - Apical hypertrophic cardiomyopathy in Pakistan: electrocardiographic,
      echocardiographic and myocardial scintigraphic features.
AB  - Apical hypertrophic cardiomyopathy is a recently recognised entity, with typical
      electrocardiographic, echocardiographic and myocardial scintigraphic features.
      Thallium imaging is more sensitive than echocardiography, but electrocardiogram
      appears to be an important clue to its diagnosis which shows changes in the mid
      precordial leads in most of the patients.

PMID- 7563574
TI  - The value of fine needle aspiration biopsy in the management of breast disease.
AB  - Fine needle aspiration biopsy is a technique used all over the world in the
      diagnosis and management of breast lumps. It is safe, quick, accurate, cost
      effective and acceptable to the patients. We reviewed 234 fine needle aspiration
      biopsies performed over a period extending from 1991-1993 for diagnosis of breast
      lesions. Majority of the patients presented with breast lumps (89.7%). On FNAB
      144 (61.4%) cases were reported as benign and 60 (25.6%) as malignant.
      Histological diagnosis was available in 116 cases. On comparison with open biopsy
      diagnosis, FNAB was found to have a sensitivity of 96.4%, a specificity of 95.5%
      and efficiency rate of 96.2%. The results of the study endorse the use of FNAB as
      an accurate and effective technique in the management of breast ailments in our
      set-up.

PMID- 7563575
TI  - Altered platelet activating factor metabolism in insulin dependent diabetes
      mellitus.
AB  - Diabetes mellitus is associated with several abnormalities of platelet function.
      Recent studies have shown that the blood level of platelet activating factor
      (PAF), a potent inducer of platelet aggregation, is elevated in insulin dependent
      diabetes mellitus (IDDM) and remains unchanged in non-insulin dependent diabetes
      mellitus (NIDDM) patients. However, the mechanism of this increase in PAF levels
      has not been determined. In this study we have measured the activity of plasma
      PAF acetylhydrolase (an enzyme that regulates PAF levels) and lipoprotein levels
      in control subjects and diabetic patients. The data presented show that plasma
      PAF acetylhydrolase activity is significantly decreased in IDDM and is not
      altered in NIDDM patients. The lipoprotein levels were similar in control and
      diabetic subjects and there was no correlation between lipoprotein levels and PAF
      acetylhydrolase activity. These results suggest that the elevated levels of PAF
      in IDDM patients could be due to a decrease in plasma PAF acetylhydrolase
      activity.

PMID- 7563576
TI  - Visceral leishmaniasis--a study of 38 cases on the basis of geographical
      distribution.
AB  - Geographical distribution of thirty-eight cases of visceral leishmaniasis (VL),
      who were diagnosed in the department of Pathology, Rawalpindi Medical College and
      two private laboratories in Rawalpindi and Islamabad is presented. Majority
      (84.2%) came from Azad Kashmir, especially from areas around Poonch (e.g.,
      Rawlakot-28.9%; Bagh-23.7%; Dirkot-5.3% and Pallandari-2.6%) and areas around
      Muzaffarabad (e.g., Chakothi-13.2% and Punja Sharif-5.3%). Only two patients
      (5.3%) belonged to Gilgit agency. Four cases came from villages around Murree,
      Rawalpindi and Abbottabad. These places are not known as endemic areas of VL. It
      is proposed that epidemiological studies for VL should be carried out in areas of
      Azad Kashmir, especially concentrating on the places from where patients keep on
      presenting for treatment in various hospitals of Rawalpindi and Islamabad.

PMID- 7563577
TI  - Diagnostic evaluation of pleural effusion and the role of needle pleural biopsy.

PMID- 7563578
TI  - Pharyngocutaneous fistula following laryngectomy.
AB  - Sixty-eight cases of stage III and IV laryngeal cancer were analysed to determine
      the frequency and management of post-operative pharyngocutaneous fistula (PCF).
      The overall incidence in our series is 8.9% (6 cases). In five patients PCF
      healed spontaneously without any surgical intervention while one patient expired
      due to concomitant other medical illness. The longest time taken by the fistula
      to heal by conservative treatment was 7 weeks. Retaining the NG tube for a longer
      period (14-16 days) and adequate and appropriate antibiotic cover reduces the
      incidence of fistula formation.

PMID- 7563579
TI  - Guidelines for anticoagulation therapy in pregnancy.

PMID- 7563580
TI  - Hepatocellular carcinoma: clinical features, evaluation and treatment.

PMID- 7563581
TI  - Jugular foramen tumours.

PMID- 7563583
TI  - Formaldehyde.

PMID- 7563582
TI  - Lansoprazole--a new proton pump inhibitor.

PMID- 7563584
TI  - Wood dust.

PMID- 7563585
TI  - [Susceptibilities of bacteria isolated from patients with respiratory infectious
      diseases to antibiotics (1990)].
AB  - These investigations have been continued since 1981. In this year the isolation
      frequencies and sensitivities to antibiotics were investigated for 654 bacterial
      strains isolated from respiratory tract infections in 20 institutions during the
      period of October 1990 to September 1991. Among Staphylococcus aureus isolated
      from inpatients, many were methicillin-resistant S. aureus (MRSA), and the
      frequency of their isolation was 56.3% for inpatients and 4.3% for outpatients.
      Of the relation to antibiotic administration, the isolation frequency of MRSA
      before administration of antibiotics was 19.6% (10/51), and after administration
      was 75.0% (27/36). The sensitivities of S. aureus to imipenem and clindamycin
      (MIC80) decreased from 0.2 microgram/ml to 64 micrograms/ml and from 0.2
      micrograms/ml to 128 micrograms/ml, respectively. We investigated year to year
      changes in the backgrounds of patients with respiratory tract infections.
      Bacterial pneumonia was 31.6% among respiratory tract infections in the period of
      the study, this trend has increase from 1989. Frequencies of different
      etiological bacteria in respiratory tract infections did not change appreciably
      from year to year, and S. aureus, Streptococcus pneumoniae and Pseudomonas
      aeruginosa were the most showing some frequent pathogens.

PMID- 7563586
TI  - [Pharmacokinetic and clinical studies of S-1108 in the pediatric field. Pediatric
      Study Group of S-1108].
AB  - S-1108 in granules, a new oral cephem antibiotic, was pharmacokinetically and
      clinically evaluated in the pediatric field and the following results were
      obtained. 1. Pharmacokinetics S-1108 was administered at single doses of 2, 3, 4,
      6 mg/kg orally and the following results were obtained on Cmax, T 1/2 and AUC,
      respectively: Cmax: 0.79, 1.03, 1.39, 1.06 micrograms/ml, T 1/2: 1.28 +/- 0.40,
      1.27 +/- 0.65, 1.10 +/- 0.29, 1.83 hrs., AUC: 2.65 +/- 0.63, 3.99 +/- 2.77, 5.25
      +/- 1.83, 5.15 micrograms.hr/ml. These values indicated a dose-dependent
      pharmacokinetic behavior. Urinary recovery rates were 12.5-30.0% in the first
      8(6) hours after administration. 2. Clinical results The clinical efficacy of S
      1108 was evaluated in 456 patients with various infections. S-1108 was
      administered at a dose of 2-4 mg/kg three time a day to most patients. The
      overall clinical efficacy rate was 95.0%. In 294 cases with identified causative
      pathogen, the clinical efficacy rate was 96.9%, and the bacteriological
      eradication rate was 89.0%. Side effects occurred in 18 (3.23%) of 558 patients
      subjected to safety analyses. The main side effect was diarrhea but those side
      effects were mild and reversible. Abnormal laboratory test results were observed
      in 25 cases, (eosinophilia and elevated GOT and GPT). These abnormalities were
      not dose-dependent and also seen with other cephems to a similar extent. No
      particular and serious problems were associated with administration of this drug.
      Based on the above results, S-1108 is considered to be very useful at a standard
      dose of 2-4 mg/kg t.i.d. against most infections encountered in the pediatric
      field out-patient clinic.

PMID- 7563587
TI  - [Clinical efficacy of sulbactam/cefoperazone for the treatment of geriatric
      patients with respiratory tract infections].
AB  - We performed clinical studies on sulbactam/cefoperazone (SBT/CPZ) for the
      treatment of geriatric patients with respiratory tract infections. Seven patients
      with pneumonia, 7 with acute bronchitis, 6 with chronic respiratory tract
      infections were treated with SBT/CPZ. The patients were administered with a daily
      dose of 2.0 g or 4.0 g for 4-14 days. The clinical responses were excellent in 3,
      good in 13, fair in 3, and poor in 1 patients. The efficacy rate was 80.0%. No
      side effects were observed in any patients, but elevations of GOT, GPT were
      observed in two cases. Causative organisms were E. coli (2 strains), P.
      aeruginosa (2), MSSA (1), MRSA (1), S. pneumoniae (1), H. influenzae (1), K.
      oxytoca (1), and E. aerogenes (1). The bacteriological effect rate was 60%. One
      strain of MRSA and one of two strains of P. aeruginosa persisted in 2 patients.

PMID- 7563588
TI  - [Clinical and bacteriological effects of cefetamet pivoxil against community
      acquired respiratory tract infections].
AB  - We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT
      PI) in community-acquired respiratory tract infections and obtained the following
      findings. 1. Of the 420 respiratory tract infection cases that were treated with
      CEMT-PI according to a same protocol at a total of 42 institutions in Tokyo,
      Kanagawa-ken, Saitama-ken and Chiba-ken from February to the beginning of April
      1994, 359 cases in which clinical evaluations were considered possible were
      selected as the subjects of the clinical study. Regarding genders of patients,
      slightly more females (56.3%) than males were included. Diagnoses given to these
      patients included laryngopharygealitis (60.7%), tonsillitis (14.2%) and acute
      bronchitis (13.6). Outpatients accounted for 94.4% of the subjects. 2. For the
      bacteriological study, a written material describing the method of collecting
      specimens, storage and transport in detail was distributed to the above mentioned
      institutions. The isolation and identification of suspected causative bacteria,
      determination of minimum inhibitory concentrations (MIC) and investigation of
      beta-lactamase production were conducted all together. Suspected causative
      bacteria were detected from 238 (66.3%) out of the 359 cases. They included 85
      strains of Haemophilus influenzae, 76 strains of Streptococcus pneumoniae, 20
      strains of Streptococcus pyogenes and 17 strains of Moraxella subgenus
      Branhamella catarrhalis. 3. Clinical efficacy rates (the ratio of those
      excellent+good) among those who were treated with 1 CEMT-PI tablet (194 mg,
      titer) twice a day was 76.5% and among those who were given 2 tablets twice a day
      was 87.4%. The improvement rate of the latter was higher at a significant level
      of P < 0.05. 4. The clinical efficacies classified by suspected causative
      bacteria (single bacterium) were 93.3% against M.(B.) catarrhalis, 91.7% against
      beta-streptococci, 87.1% against H. influenzae and 78.4% against S. pneumoniae,
      etc. Though 7 (9.2%) of the 76 strains of S. pneumoniae were benzylpenicillin
      (PCG)-insensitive S. pneumoniae (PISP), the bacteriological efficacy was assessed
      either excellent or good in all of the 7 patients from whom PISP were detected.
      The clinical efficacy was assessed 100.0% in those from which a plural number of
      bacteria were detected. The 13 cases from which small numbers of Staphylococcus
      aureus was detected with other bacterium were also included in these cases.

PMID- 7563589
TI  - Ofloxacin concentrations in serum, saliva and pleural effusion of patients with
      pulmonary tuberculosis and lung cancer.
AB  - The ofloxacin (OFLX) concentration in serum, saliva and pleural effusion was
      measured in 12 patients with pleural effusion after oral administration at a dose
      of 200 mg three times a day (600 mg daily). Three patients had non-small cell
      lung cancer and the others had pulmonary tuberculosis. The mean OFLX levels in
      the serum, saliva and pleural effusion at 2 hours after the first administration
      on day 3 was 3.15 +/- 1.52, 3.36 +/- 2.23 and 2.86 +/- 1.77 micrograms/ml
      respectively. There was a strong correlation among these concentrations. The OFLX
      concentration of pleural effusion was predictable from that of saliva. A 3-day
      oral administration is sufficient to achieve the OFLX level of pleural effusion
      similar to that of the serum. It is possible that OFLX is effective for pleuritis
      caused not only by common infectious pathogens but also by Mycobacterium
      tuberculosis.

PMID- 7563590
TI  - [Cellular biology of Reed-Sternberg cells in Hodgkin's disease].

PMID- 7563591
TI  - [Platelet (P)-selectin: its basics and clinical implications].

PMID- 7563592
TI  - [Trial of combined cytosine arabinoside with granulocyte colony-stimulating
      factor therapy or refractory acute myeloid leukemia].
AB  - Thirteen cases, including 10 relapse cases, of refractory acute myeloid leukemia
      (AML) (aged 17-70, median 46) by cytosine arabinoside (Ara-C) combined with
      granulocyte colony-stimulating factor (G-CSF) simultaneously to enhance the
      sensitivity to Ara-C. Low dose Ara-C (10-40 mg/day) combined with G-CSF was
      administered in most of them. Complete (CR) and partial remission (PR) were
      achieved in 5 and 4 patients, respectively, and response (CR + PR) rate was
      69.2%. We obtained 5 CRs and 3 PRs in 10 patients with relapsed AML. However, CR
      and PR duration was short in all cases. None of the 3 patients with MO, AML
      transformed from myelodysplastic syndrome (MDS), and de novo AML with trilineage
      myelodysplasia (TMDS) had any response. There was no leukemic colony formation in
      the culture medium containing G-CSF in the nonresponding patients. The
      combination therapy caused severe myelosuppression, and most patients experienced
      prolonged neutropenia, and suffered from infections. In some patients enhanced
      chemosensitivity of leukemic cells induced by G-CSF was indicated but, the effect
      of this approach must be determined by large scale controlled studies.

PMID- 7563594
TI  - [Acute myelomonocytic leukemia complicated with syndrome of inappropriate
      secretion of antidiuretic hormone, nephrotic syndrome, and hemophagocytic
      syndrome].
AB  - A 59-year-old man was admitted to our hospital because of fever in August 1991.
      Bone marrow showed normocellularity with 41.5% of CD13, 14, 33 positive blasts,
      and a diagnosis of AMMoL was made. Laboratory investigation revealed hyponatremia
      and elevated serum ADH level, indicating the syndrome of inappropriate secretion
      of antidiuretic hormone (SIADH). Intensive chemotherapy successfully induced
      hematological complete remission and his serum sodium level became normal. In
      February 1992, he developed proteinuria and findings were consistent with
      nephrotic syndrome (NS). Renal biopsy specimen showed membranous proliferative
      glomerulonephritis and massive infiltration of macrophages, and his serum
      interleukin 6 level was elevated. Five months later, he suffered from
      pancytopenia and elevation of biliary enzymes with increase of hemophagocytic
      histiocytes in his bone marrow (hemophagocytic syndrome). He transiently
      responded to low dose chemotherapy but he died due to severe infection. It is
      interesting that association between macrophages and/or cytokines with these
      various complications was suggested in AMMoL.

PMID- 7563593
TI  - [Continuous infusion therapy with low dose cytosine arabinoside and etoposide in
      acute myelogenous leukemia patients hardly tolerable for intensive combination
      chemotherapy].
AB  - We evaluated the efficacy of continuous drip infusion therapy with low dose
      cytosine arabinoside (AraC) and etoposide (VP16) in poor-condition patients with
      acute myelogenous leukemia (AML). Patients' age ranged from 19 to 85 years with a
      median of 63 years. Principally they received continuous drip infusion for 14
      days with AraC (20 mg/day) and VP16 (50 mg/day). Complete remission (CR) rate was
      58.3% (7/12) in untreated cases, 33.3% (2/6) in refractory cases to the standard
      chemotherapy, and 28.6% (2/7) in relapsed cases. The duration of CR ranged from
      1.5 to 20 (+) months (median 8) in untreated group and from 2 to 22 months
      (median 10) in refractory and relapsed groups. Adverse effects such as
      gastroenterological symptoms appeared but were tolerable. Although infections due
      to myelosuppression appeared in 22 of 25 cases, they were well controlled by
      antibiotics. Chemotherapy-related death was not observed. Although CR rate and CR
      duration of this therapy were not sufficiently high, the regimen was effective in
      some patients with refractory or relapsed AML. Further studies are required to
      establish the efficacy, indication and safety of this treatment.

PMID- 7563595
TI  - [Postpartum parvovirus B19-associated acute pure red cell aplasia and
      hemophagocytic syndrome].
AB  - A 30-year-old postpartum woman was admitted to our hospital because of
      progressive anemia, malaise, night sweating, headache and low grade fever which
      began 9 days after delivery (day 0). She had normocytic hypochromic anemia
      accompanied with marked decrease in reticulocytes. In addition, a temporary
      decrease in platelets and white blood cells especially neutrophils were observed.
      Bone marrow smears showed an apparent decrease in erythroid cells and the
      presence of giant proerythroblasts (1.2%) as well as hemophagocytes (1.2%). IgM
      and IgG antibody against human parvovirus B19 (HPV) was detected on day 22 of the
      disease although negative results were obtained on day 3. The presence of the
      virus in the blood on admission was confirmed by dot-blot analysis. Thus, this
      case was diagnosed as acute pure red cell aplasia and hemophagocytic syndrome
      caused by HPV infection. This patient had been given iron for iron deficiency
      anemia before delivery and the iron deficiency was still present after the
      episode of the present disease although the iron metabolism data was perturbed
      during the disease. These findings suggest that HPV could cause acute pure red
      cell aplasia not only in patients with hemolytic anemia but also in patients with
      iron deficiency anemia or after acute bleeding. Furthermore it is suggested that
      pancytopenia often observed on HPV infection could be at least partly caused by
      hemophagocytic syndrome.

PMID- 7563596
TI  - [Successful treatment of recurrent chronic myelogenous leukemia in allogeneic
      marrow transplant recipient with the donor leukocyte transfusion, without
      induction of acute graft-versus-host disease].
AB  - A 45-year-old female developed cytogenetic relapse of chronic myelogenous
      leukemia 4 years after allogeneic bone marrow transplantation. To induce a graft
      versus-leukemia effect, peripheral blood buffy-coat cells were collected from the
      original marrow donor during 5 rounds of leukapheresis over 3 weeks, and 2.47 x
      10(8) cells/kg were infused into the patient. Acute graft-versus-host disease
      (GVHD) did not develop even after an interval of 50 days from the last donor
      leukocyte transfusion (DLT). However, karyotypic analysis of bone marrow cells
      performed on the same day showed an apparent decrease in the proportion of Ph1
      chromosome-positive cells (1/20) among all dividing cells, compared with the
      proportion (13/20) observed before DLT. At the same time, the proportion of red
      blood cells (RBCs) of donor origin among the peripheral RBCs of the patient,
      which was less than 10% before DLT, began to rise and reached 100% at 4 months
      after DLT. The karyotype of bone marrow cells obtained on day 90 after DLT was
      completely normal. Although chronic GVHD of the buccal mucosa and liver developed
      in association with pancytopenia on day 71 after DLT, this improved rapidly with
      oral administration of cyclosporine. The clinical course of this patient suggests
      that acute GVHD is not a prerequisite for elimination of Ph1-positive cells by
      DLT.

PMID- 7563597
TI  - [Secondary myeloid/natural killer cell acute leukemia appeared in multiple
      myeloma treated with melphalan].
AB  - A 67-year-old woman was treated with MP-P therapy and combination chemotherapy
      for multiple myeloma IgG-lambda type. After the therapy for about three years,
      pancytopenia developed. Bone marrow aspiration study revealed a few of myeloma
      cell and many atypical cells showing promyelocytic feature. Chromosomal
      abnormality was 46, X, -X, +8, -13, +mar. CD33 and CD56 were positive, but CD16
      and HLA-DR were negative. We diagnosed as multiple myeloma complicated with
      secondary myeloid/natural killer (NK) cell acute leukemia. After she had been
      treated with low dose etoposide for leukemia, she obtained complete remission.
      But since myeloma progressed and the amount of M protein was increased, she was
      treated with dexamethasone and low dose etoposide, resulting in a decrease in the
      amount of M protein. After that, because of leukemic cell re-proliferation, she
      was treated with etoposide. However, she died of sepsis due to severe
      myelosuppression. This case was interesting one in coexist of multiple myeloma
      and secondary myeloid/NK cell acute leukemia, and those affecting her clinical
      course each other.

PMID- 7563599
TI  - [Bence Jones type multiple myeloma showing diffuse infiltration to the dura mater
      by myeloma cells].
AB  - A 62-year-old man with aleukemic Bence Jones type multiple myeloma who developed
      neurologic abnormalities is reported. After admission, consciousness disturbance
      appeared and a lumbar puncture obtained M-protein. Though brain CT showed no
      abnormal findings except a punched out lesion of the temporal bone, MRI disclosed
      remarkable enhancement of the dura mater. Meningeal involvement by myeloma cells
      without leukemic blood picture is very rare though it is common in other
      lymphoproliferative disorders such as acute lymphocyte leukemia and malignant
      lymphoma. We report a case of BJ type multiple myeloma with meningeal involvement
      due to diffuse infiltration to the dura mater and discuss a possible mechanism of
      meningeal involvement in this patient.

PMID- 7563598
TI  - [Spinal canal bleeding in hemophilia A].
AB  - Case 1: Sensory and motor paralysis below the L3 level developed in a moderate
      hemophilia A due to spinal epidural bleeding following lumbar anesthesia for the
      resection of retro-peritoneal hematoma. By the treatment with cryoprecipitates,
      the patient recovered to walk with sticks after laminectomy. Case 2: the patient
      had severe hemophilia A with 220 Bethesda units/ml of inhibitor. The patient
      suffered from epidural and intramedullary spinal bleeding from C3 to C7 and
      developed tetraplegia. Since the inhibitor titer was high, infusion therapy with
      FEIBA was performed. Paralysis gradually reduced to the T5 level, but the patient
      had both sensory and motor paralysis of the extremities. It is required that an
      effective hemostastic treatment for spinal canal bleeding in hemophilia A with
      high-responder inhibitor is established.

PMID- 7563600
TI  - [Transient promyelocytic expansion in primary myelofibrosis].
AB  - A 46-year-old man with primary myelofibrosis developed polyarthralgia. Marked
      hepatosplenomegaly was noted, and hematological examinations revealed a white
      cell count of 25,600/microliters with 42% promyelocytes and thrombocytopenia. The
      promyelocytes were positive for CD4 antigen and nonspecific esterase as well as
      peroxidase. Cytogenetic analysis of circulating mononuclear cells showed the
      trisomy of No. 22 chromosome in 3 of 5 cells examined. Four months later, the
      patient became asymptomatic, and hematological picture and hepatosplenomegaly
      returned to the original level. This is the first report describing the transient
      promyelocytic expansion in myeloproliferative disorders.

PMID- 7563601
TI  - [Multiple myeloma developing myelodysplastic syndrome with thrombocytosis].
AB  - A 64-year-old woman with multiple myeloma, IgG lambda type Durie-Salmon Stage II,
      was admitted because of gradually developing anemia and increased blasts with
      abnormal karyotype in her bone marrow after 10 years of treatment. The
      chromosomal analysis showed 44, XX, del(5q), del(7q), -9, add(12p), -21, typical
      of secondary MDS due to the cumulative alkylating agents. Thrombocytosis
      concomitantly occurred with emergence of chromosomal abnormality, but the serum
      interleukin 6 level was not elevated, which suggested that it was related to
      development of secondary MDS.

PMID- 7563602
TI  - [Acute promyelocytic leukemia following ulcerative colitis].
AB  - We report a case of acute promyelocytic leukemia (APL) following ulcerative
      colitis (UC). A 23-year-old man was diagnosed as UC in January 1991 and had been
      treated with salazosulfapyridine and prednisolone with good effect. In September
      1993, he developed bleeding tendency and a diagnosis of APL with disseminated
      intravascular coagulation was made based on the results of bone marrow aspiration
      and coagulation profile. Complete remission was achieved with All-trans retinoic
      acid together with combined chemotherapy. He died of sepsis during consolidation
      chemotherapy in December 1993. Autopsy revealed no recurrence of UC.

PMID- 7563604
TI  - [Chromosomes, morphologic subtypes and their prognostic evaluation in acute non
      lymphocytic leukemia].
AB  - Cytogenetic and morphological analyses were performed on 55 adult patients (34
      males, 21 females) with acute non-lymphocytic leukemia (ANLL) diagnosed between
      1986 and 1992, and the results were studied with regard to therapeutic response
      and prognosis. Eleven patients had M1 (20%), 14 had M2 (25.5%), 14 had M3
      (25.5%), 7 had M4 (12.7%), 3 had M5 (5.5%), 5 had M6 (9.1%) and one had M7
      (1.8%). The overall incidence of chromosomal abnormalities were 65.5% including
      10 cases (18.2%) with t (8;21), 12 (21.8%) with t (15;17), 5 (9.1%) with
      pseudodiploid, 3 (5.5%) with hyperdiploid, 2 (3.6%) with hypodiploid and 4 (7.3%)
      with abnormalities of 5 or 7 chromosomes. Outcomes were analyzed in 45 patients.
      36 patients (80%) achieved complete remission (CR). All 12 patients with M2
      entered CR, and they showed a significantly longer median survival than M1. The
      median survival of 10 patients with t (8;21) was significantly longer than that
      of patients with t (15;17). However, therapeutic response and prognosis did not
      correlate with either chromosomal status (NN, AN, or AA) or with age-groups (> or
      = 60, < 60). These results confirmed that morphological subtypes and certain
      types of chromosomal abnormality are important variables in determining the
      prognosis of adult patients with ANLL.

PMID- 7563603
TI  - [Expression of a proliferation associated-nuclear antigen defined by Ki-67
      monoclonal antibody in childhood acute leukemia].
AB  - The growth fraction of childhood acute leukemia was evaluated by the
      immunostaining with the monoclonal antibody "Ki-67", which reacts with a nuclear
      antigen in proliferating cells. Ki-67 labeling rates (the percentage of Ki-67
      positive cells in the total cells analyzed) greatly varied from patient to
      patient (0.0% approximately 49.2%). The mean value of the Ki-67 labeling rates
      was significantly higher in ALL than in ANLL (23.6% vs 5.6%, p < 0.001). In ALL,
      the Ki-67 labeling rates correlated with the proportion of S-phase cells
      determined by DNA flow cytometry (FCM) (r = 0.82) High Ki-67 labeling rates were
      preferably seen in ALL with favorable prognostic factors, although the
      correlation was not statistically significant. These results suggest that Ki-67
      labeling rates reflect the differences in proliferative activity of bone marrow
      blast cells in childhood acute leukemia and is useful to determine the treatment
      schedule of cycle specific drugs.

PMID- 7563605
TI  - [Prostaglandin E1 bladder instillations for late-onset hemorrhagic cystitis
      following allogeneic bone marrow transplantation].
AB  - Between July, 1990 and March, 1994, 31 patients with hematological malignancies
      or severe aplastic anemia underwent allogeneic bone marrow transplantation (BMT)
      at the Second Department of Internal medicine, Chiba University Hospital. Among
      the 29 evaluable patients who survived over 100 days after transplant, 11
      patients (37.9%) developed late-onset hemorrhagic cystitis with a median time of
      onset of 57 days (range 11-205) from BMT. Adenovirus type 11 was isolated from
      the urine of 4 patients. Five patients recovered with fluid hydration and forced
      diuresis, while 6 patients had persistent gross hematuria with clot formation, 5
      of whom also developed hydronephrosis. Seven-day courses of 500 micrograms
      prostaglandin E1 (PGE1) bladder instillations was initiated to control hematuria
      in these 6 patients. Complete resolution of gross hematuria was achieved in 4,
      and partial response with decreased clot formation and partial clearing of the
      urine was observed after 4 of 9 courses of the treatment. Although all patients
      experienced bladder spasm or lower abdominal pain during the PGE1 instillations,
      these symptoms were manageable with sedative drugs and morphine. No systemic side
      effect was apparent. PGE1 bladder instillations is a safe and useful treatment
      for severe, life-threatening late-onset hemorrhagic cystitis after allogeneic
      BMT.

PMID- 7563606
TI  - [Autopsy cases of cytomegalovirus interstitial pneumonitis following bone marrow
      transplantation].
AB  - We investigated the relevance of cytomegalovirus (CMV) to interstitial
      pneumonitis (IP) using formalin-fixed and paraffin-embedded lung tissues obtained
      from 12 autopsy cases who died following bone marrow transplantation (BMT) from
      May 1985 to March in 1992. The lung tissues were examined by hematoxylin and
      eosin (H.E.) staining, immunohistochemistry with monoclonal antibodies (DDG9,
      CCH2) and polymerase chain reaction (PCR) for amplifying human CMV DNA. Eight of
      12 cases were clinically diagnosed as IP. The 4 cases showed no signs of IP, and
      their tissues were used as controls. H.E. staining revealed inclusion bodies in
      two of the eight and only severe fibrosis in the other six. In 4 of the 6 cases,
      however, CMV was identified by immunohistochemistry or PCR. We concluded that the
      relevance of CMV in the genesis of IP is often overlooked by H.E. staining alone.
      Immunohistochemistry and PCR are useful in examining tissues which are suspected
      of CMV-IP.

PMID- 7563607
TI  - [Multicentric Castleman's disease with lymphoid interstitial pneumonia died of
      aggressive course with adult respiratory distress syndrome].
AB  - A 49-year-old man was admitted to our hospital with anemia and
      hypergammaglobulinemia. Physical examination revealed superficial lymph node
      swelling and no hepatosplenomegaly. Laboratory findings showed WBC
      5,300/microliters with normal hemogram, microcytic and hypochromic anemia. Total
      protein was 11.5 g/dl and immunoglobulinemia (IgG 10,100 mg/dl, IgA 295 mg/dl,
      IgM 160 mg/dl) was observed without M-component in serum and urine. The CD4/CD8
      ratio of lymphocyte subsets was 0.58 and the tuberuculin skin test was negative.
      Urinary protein was positive and renal biopsy disclosed plasma cell infiltration.
      Lymph node biopsy revealed multiple lymphoid follicles and infiltration of plasma
      cells in the interfollicular areas. A diagnosis of multicentric Castleman's
      disease (MCD) was made baredon clinical findings and lymph node biopsy. After
      therapy with plasmapheresis and the CHOP regimen, he was given etoposide.
      Although discharged with clinical improvement and a decrease of serum IgG, he was
      readmitted because of pyrexia after 4 days and died of pneumonia with adult
      respiratory distress syndrome. The autopsy revealed lymphoid interstitial
      pneumonia. It seems important to notice that some of MCD have poor prognoses
      because of accompanying immunodeficiency.

PMID- 7563608
TI  - [Peripheral blood stem cell transplantation for rapidly spreading myeloma].
AB  - We report a case of rapidly spreading myeloma of immature cell morphology treated
      by peripheral blood stem cell transplantation (PBSCT). A 54-year-old man had a
      right orbital tumor, which subsequently was removed and proved to be
      plasmacytoma. Three years later a mass lesion appeared in his left lung and
      bilateral kidneys. The specimen obtained at lung biopsy confirmed the diagnosis
      of plasmacytoma. Serum M-protein, IgG lambda was increased, but there was no
      increase in plasma cells in the bone marrow. Since chemotherapy with VAD did not
      show any improvement, a high dose etoposide (500 mg/day, 4 days) was
      administered. When bone marrow suppression recovered, PBSCs were harvested (3.3 x
      10(6)/kg). After conditioning therapy with cyclophosphamide (2.0 g/day, 2 days),
      etoposide (200 mg/day, 3 days) and ranimustine (200 mg/day, 2 days), the stored
      PBSCs were injected. Minor response was obtained and he was discharged. 2 months
      thereafter, it was found that plasma cells increased in the bone marrow. He died
      of pulmonary bleeding soon. Autopsy revealed immature plasma cell infiltration in
      multiple organs including the heart, liver, spleen, kidneys, intestine, bone and
      bone marrow.

PMID- 7563609
TI  - [Therapy-related leukemia with t(8;21) initially diagnosed as MDS (RAEB in T)].
AB  - A 64-year-old woman was diagnosed as having myelodysplastic syndrome (MDS) at 45
      months after receiving radiotherapy for advanced carcinoma of the uterine cervix.
      We chose low dose therapy of SPAC and ACR because of the diagnosis as therapy
      related MDS and the existence of radiation colitis. She obtained minor response,
      but two months later she transformed to AML (M2). The interval between low dose
      therapies was getting shorter and shorter, so we tried intensive chemotherapy
      consisting of BHAC, ACR and 6MP. Blast numbers were reduced, but she died of
      sepsis and intestinal bleeding. The patients of MDS with t(8;21) and the patients
      of therapy-related AML (tAML) with t(8;21) are very rare. According to the
      literature, only karyotype is a prognostic factor in AML/MDS with t(8;21). And
      diagnosis by the criteria of FAB classification is of little value regarding
      clinical progress. That is to say, if the patient has only t(8;21) or karyotypic
      abnormalities which are of little value in prognosis, such as the loss of a sex
      chromosome, it must be treated as de novo AML, but if patient has karyotypic
      abnormalities such as -5, 5q-, -7, 7q-, and/or multiple (complicated)
      abnormalities, we must accept that the prognosis is poor and must treat it as
      ordinary MDS/tAML.

PMID- 7563611
TI  - [Vancomycin-induced thrombocytopenia for MRSA pneumonia].
AB  - Thrombocytopenia occurred after 17 days of administration of vancomycin (VCM) in
      2 cases of MRSA pneumonia. The drug lymphocyte stimulation test using VCM and
      anti-platelet antibody were negative for these 2 cases. However, platelet bound
      IgG significantly increased and the total number of immature megakaryocytes in
      the bone marrow increased. Corticosteroid administration after VCM was very
      effective for thrombocytopenia. In case 1, thrombocytopenia occurred three times
      after using of VCM, suggesting to have been induced by VCM. The mechanism of
      thrombocytopenia was immunological destruction. It has been reported that VCM
      induced neutropenia might be induced via an immunological mechanism. We reported
      here 2 cases of thrombocytopenia induced by VCM, which is frequently used for
      MRSA pneumonia.

PMID- 7563610
TI  - [Intermittent-dose ara-C/daunomycin therapy combined with cyclosporin-A and G-CSF
      led to a fourth remission in a patient with acute promyelocytic leukemia].
AB  - A 50-year-old female was admitted with acute promyelocytic leukemia (APL) in
      August, 1988. She was treated with behenoyl-ara-C, daunomycin, 6-mercaptopurine
      and prednisolone (BH-AC.DMP), which led to a complete remission. Thereafter, she
      was treated with 2 courses of BH-AC.DM and discharged from hospital.
      Intensification therapy was performed twice a year, with 1 course of BH-AC.DM and
      5 courses of intermittent-dose ara-C/mitoxantrone which ended in March, 1992. She
      had a relapse in September, 1993 and was treated with all-trans retinoic acid,
      which led to a second remission. A second relapse occurred in May, 1994, and
      intermittent-dose ara-C/mitoxantrone, combined with granulocyte colony
      stimulating factor (G-CSF), led to a third remission. However, she had a third
      relapse in September, 1994. She was treated with a trial of G-CSF (300
      micrograms/body, day 1-7), to stimulate dormant leukemic cells to enter the cell
      cycle, and cyclosporin-A (78 mg/kg, day 2-5), in order to overcome daunomycin
      resistance in refractory leukemia, combined with daunomycin (45 mg/m2, day 3-5)
      and ara-C (1.4 g/m2, day 3-7), after obtaining informed consent. The fourth
      remission needed 46 days after combination chemotherapy because of severe
      myelosuppression. It was suggested that intermittent-dose ara-C/daunomycin
      therapy combined with G-CSF and cyclosporin-A may be useful for relapsed and
      refractory leukemia.

PMID- 7563612
TI  - [A HBV carrier with fulminant hepatitis complicated by ATL, multiple myeloma and
      thyroid cancer].
AB  - A 75-year-old female, born in Tochigi Prefecture, was admitted because of lumbago
      in August of 1991. The leukocyte count was 11,800/microliters with 22.5% atypical
      lymphocytes. We demonstrated a lymphocyte surface marker, ATL-associated antigen,
      and proviral DNA. We also identified 2.60 g/dl of serum monoclonal protein, found
      to be IgG, lambda type, and punched out lesions in the skull. We made a diagnosis
      of ATL. She was also a HBV carrier. The patient was treated with a modification
      of CHOP therapy, because of increasing atypical lymphocytes in the peripheral
      blood in November of 1992. She died of acute hepatitis, suddenly, in March of
      1993. Autopsy revealed multiple myeloma, fulminant hepatitis and occult thyroid
      cancer in addition to ATL.

PMID- 7563613
TI  - [Chemotherapy with concomitant IFN treatment in three HBV carriers (mutant
      strain) with malignant lymphoma].
AB  - Intensive multidrug chemotherapy with concomitant IFN was performed in three
      hepatitis B virus (HBV) carriers with malignant lymphomas. All of the patients
      were HBsAg+, HBsAb-, HBcAb+, HBeAg- and HBeAb+ (mutant strain+). HBV-DNA
      polymerase (DNA-P) was normal at the beginning of chemotherapy, and complete
      response was achieved with CO-BLAM chemotherapy (without PDN) in all cases. In
      case 1, a slight elevation of DNA-P and normal GOT and GPT was observed after IFN
      alpha was started during the third course. IFN-alpha was administered twice a
      week. In case 2, elevation of DNA-P and normal GOT and GTP were noted at the end
      of the 5th course, then daily IFN-alpha was started. In case 3, daily IFN-alpha
      was started during the 3rd course because of elevation of DNA-P. It was possible
      to prevent severe liver damage by administering IFN immediately after the
      elevation of DNA-P, since DNA-P elevation is noted before GOT and GPT elevation.
      The detection of the HBV mutant strain could be helpful in the treatment of
      HBsAg+ and HBeAb+ patients. In all of three patients, DNA-P, serum GOT and GPT
      normalized quickly after the administration of IFN-alpha. Severe hepatitis did
      not develop.

PMID- 7563614
TI  - [Aplastic anemia with giant splenomegaly and myelofibrosis successfully treated
      with antilymphocyte globulin].
AB  - Severe aplastic anemia was diagnosed in a 58-year-old female because of
      pancytopenia with leukocyte count 700/microliters, hemoglobin 3.4 g/dl, platelet
      count 4.2 x 10(4)/microliters and fatty hypoplastic bone marrow in August 1992.
      In January 1993, she was admitted with an abdominal skin infection caused by
      pseudomonas aeruginosa. After treatment of the infection, antilymphocyte globulin
      was given at a dose of 2,000 mg/day for four consecutive days in July 1993. This
      resulted in a gradual but steady improvement in her hematological data. In
      February 1995, her leukocyte count increased to 2,000/microliters, hemoglobin to
      15.2 g/dl and platelet count to 11.0 x 10(4)/microliters. Although no
      splenomegaly or myelofibrosis was found previously, from April 1993, the spleen
      enlarged and was palpable 10 cm below the costal margin. Her bone marrow biopsy
      in June 1993 revealed prominent myelofibrosis. Thereafter no changes were found
      in these features. Splenomegaly and myelofibrosis are characteristic of primary
      myelofibrosis and although the relationship is uncertain, there is no previous
      report on aplastic anemia with splenomegaly and myelofibrosis.

PMID- 7563615
TI  - [Double cancer in patients with adult T cell leukemia].
AB  - We have studied the incidence and characteristics of associated neoplasms in 210
      ATL patients. Twelve patients had other primary neoplasms and the incidence of
      double cancer was 5.7%. The additional malignancies in ATL patients consisted of
      4 cases of stomach, 3 cases of colon and one of each lung, ovary, uterus, liver
      and bladder cancer. In metachronous double cancer patients, the neoplasm was
      found before the time of diagnosis of ATL in 5 out of 6 patients.
      Immunodeficiency due to HTLV-I infection as well as chemotherapy for the
      preceding neoplasm are suggested to be related to the leukemogenesis of ATL.

PMID- 7563616
TI  - [The structure and function of renal tubulointerstitium].

PMID- 7563617
TI  - [The structure and function of the renal interstitial cells].
AB  - The renal interstitial cells consist of fibroblast-like cells, lipid-laden
      interstitial cells, macrophages, interstitial dendritic cells and perivascular
      cells. The fibroblast-like cells are mainly located in renal cortex and medulla,
      and have long cytoplasmic processes forming a reticular network between the
      tubules and capillaries. In disease state, interstitial cells show expressions of
      HLA-class 2 antigen, ICAM-1 and VCAM-1, and the expressions are related with
      leukocyte infiltrate and tubulitis. In tubular injury and obstruction, the
      proliferation of interstitial cells occurs around damaged tubules, and form a
      lymphatic system. In the interstitial fibrosis, interstitial and tubular
      epithelial cells secrete procollagen and interstitial cells have the action of
      resolving them. Therefore, the relationship between interstitial fibrosis and
      interstitial cells is not yet clear. The medullary interstitial cells have
      receptors for angiotensin 2 or bradykinin and secrete PGE2. The interstitial
      cells show an interaction of blood components and tubular epithelial cells.

PMID- 7563618
TI  - [Microcirculation in renal interstitium].
AB  - Microcirculation in the renal interstitium plays an important role in the
      regulation of urinary sodium excretion and thus in the control of blood pressure.
      An increase in renal interstitial hydrostatic pressure caused by renal perfusion
      pressure elevation induces pressure natriuresis by decreasing tubular
      reabsorption. Chronic NO inhibition in the medullary interstitium decreases
      medullary blood flow and induces sodium retention and blood pressure elevation.
      Chronic medullary, but not intravenous, infusion of ACE inhibitor restores the
      impaired pressure natriuresis by improving medullary microcirculation in SHR. The
      tubuloglomerular feedback signal transmission is dependent on Cl concentration in
      the juxtaglomerular interstitium and its sensitivity is modulated by pressure
      there in.

PMID- 7563619
TI  - [Role of interstitium in the regulation of renal tubular solute transport].
AB  - The physiological significance of the renal interstitium is reviewed with special
      reference to solute transport. The renal tubules and vasculatures participate in
      essential parts of the nephron functions. The renal interstitium, interposing
      among these structures, regulates solute transport across the renal tubules. In
      the renal cortex, changes in the interstitial pressure modulate the proximal
      tubular fluid reabsorption via paracellular shunt pathways. In the renal medulla,
      the interstitium may play an important role in the lateral diffusion of solutes
      and water, contributing to the mechanisms of urine concentration, as well as,
      medullary potassium recycling and ammonia excretion.

PMID- 7563620
TI  - [Receptors and its signal transduction pathway in the renal interstitial cells].
AB  - There are several types of renal interstitial cells, such as fibroblast,
      monocyte/macrophage, lymphocyte, dendritic cell, and so on. These cells in the
      interstitium probably modulate changes in tubular repair, including cell
      proliferation, cell mitosis, fibrosis, immune cell infiltration and interstitial
      fibrosis through a complex cytokine and/or mediator network. These factors bind
      to cellular receptors, and then they activate signal transduction pathways, and
      result in expression of several information such as cell proliferation, mitosis
      and so on. In this paper, we attempt to describe some receptors and its signal
      transduction pathway in the renal interstitial cells.

PMID- 7563621
TI  - [Electrolyte metabolism in renal tubules].
AB  - Obese, diabetic and hypertensive populations have an increased prevalence of
      hyperinsulinemia and insulin resistance with respect to glucose metabolism.
      Insulin is thought to contribute to hypertension by sodium retention in the
      kidney. Here we describe the direct effect of insulin on renal tubular transport.
      The ascending thin limb of Henle's loop (ATL) plays an important role in
      concentrating urine. However, it is still controversial whether Na+ reabsorption
      in this nephron segment is an active process or a passive one. Moreover hormonal
      regulation of Cl- transport in the ATL is completely unknown. Therefore we also
      describe the mechanism of Na+ transport and hormonal regulation of Cl- transport
      in the ATL.

PMID- 7563622
TI  - [Biosynthesis of hormones in renal tubular and interstitial cells].
AB  - Renal tubular and interstitial cells produce various hormones. Renin is
      synthesized in juxtaglomerular cells which are derived from the media of the
      afferent arteriole. Endothelin-1 is formed in mesangial cells of glomeruli and
      inner medullary collecting duct. In contrast, endothelin-3 synthesis is observed
      in glomeruli and all the tubule segments. 1 alpha-hydroxylase is present in
      proximal tubule and catalyzes production of 1,25(OH)2D. PGE2 is synthesized in
      glomeruli, all the tubule segments, and interstitial cells. The major production
      sites of PGF2 alpha and 6-keto-PGF1 alpha are glomeruli and medullary collecting
      duct. Kallikreins are mainly produced in connecting tubule. The cells responsible
      for erythropoietin synthesis are thought to be interstitial cells which are
      localized around the proximal tubule.

PMID- 7563623
TI  - [Growth factors in tubular cells].
AB  - Tubular cells are a major source of growth factors in the kidney, while the
      growth factors may play a crucial role for maintaining the histological structure
      or functions of renal tubulus. EGF, IGF-1 and HGF are important for the
      development of tubular segment, renal hypertrophy, regeneration after acute
      tubular necrosis and renal cyst formation. In contrast, TGF-beta is closely
      related to tubulo interstitial fibrosis. Since the tubulo interstitial lesions
      determine the progression or prognosis of the renal diseases, the regulation of
      these growth factors may be needed for the prevention of the irreversible tubular
      injury or for the regeneration of tubular cells.

PMID- 7563624
TI  - [Immune reactions that mediate tubulointerstitial nephritis].
AB  - Experimental autoimmune tubulointerstitial nephritis (TIN) is induced by
      immunization with TBM antigen and adjuvant in guinea pigs, rats, and mice. In
      animal models, both anti-TBM autoantibody and TBM-sensitized T cells have
      important roles in development of TIN. Antibodies deposited on TBM bind with
      complements, and these complexes induce infiltration of macrophages and
      leukocytes into interstitium. And, then, lymphocytes infiltrate into the
      inflammatory lesions. In these lesions, inter-cellular adhesion molecule-1 (ICAM
      1) is expressed within peritubular endothelia and tubular epithelia. There are
      several subpopulations of TBM-specific T cells associated TIN. One is Helper T
      cells (CD8+), they induce cytotoxic T cells which is CD8 positive and have
      cytotoxic activity against tubular epithelia. The function of cytotoxic T cells
      is downregulated by suppressor T cells.

PMID- 7563625
TI  - [Hypertrophy and hyperplasia of renal tubular interstitial cells--regulatory
      factors].
AB  - Renal tubular cells do not proliferate under normal intact conditions, whereas a
      marked regeneration is evident when tubular cells are injured by renal toxins or
      by ischemia. In case of compensatory renal growth too, hyperplasia of renal
      proximal tubular cells is observed. Various growth factors, including epidermal
      growth factor (EGF) and insulin-like growth factor-I (IGF-I) seem to be involved
      in renal regeneration, however, the physiological role of these growth factors
      for the natural course of the renal regeneration have yet to be established.
      Hepatocyte growth factor (HGF), a potent mitogen for cultured renal tubular
      cells, may function as a renotropic factor, which enhances regeneration of the
      kidney. Once renal tubular cells are damaged by some agents, HGF mRNA, HGF
      activity and DNA synthesis of renal tubular cells are sequentially increased.
      Since both HGF mRMA and HGF protein are localized in renal interstitial cells,
      HGF seems to act on the tubular cells as a paracrine mediator. In addition to
      these results, HGF has multiple biological functions. This suggests that HGF
      possesses biological activities essential for renal regeneration.

PMID- 7563626
TI  - [Tumorigenesis of kidney tubule].
AB  - Renal cell carcinoma is derived from renal tubule, blastematous tubule or
      nephrogenic rest. Most common sporadic clear cell tumors have structural changes
      of the chromosomes, such as the cancer suppressor genes at 3p14, 3p21 or 3p25
      (VHL gene). Cytogenetically, clear cell tumor (non papillary tumor) initially
      develops as a cancer, while papillary tumor progresses sequentially from atypical
      tubule to adenoma to carcinoma. Papillary tumors demonstrate numeric changes in
      the chromosomes. Renal cell carcinoma complicated with acquired renal cysts in
      dialysis patients tends to develop from papillary tumor. However, the exact
      mechanism inducing these genetic changes remains to be clarified.

PMID- 7563627
TI  - [Recent advances of studies on interstitial nephritis--definition and
      pathogenesis].
AB  - An abbreviated history describing our understanding of the interstitial nephritis
      was outlined in the present report. Interstitial nephritis has been recognized
      with increasing frequency. This nephritis is a diverse group of renal disorders
      in which the predominant morphologic changes occur in the interstitium included
      tubules. Recent explosive advances in immunological studies and molecular
      biological techniques have greatly expanded a study on the mechanisms of
      interstitial fibrosis.

PMID- 7563629
TI  - [Symptoms in patients with tubulo-interstitial nephritis].
AB  - High dosages of nephrotoxic drugs in elderly patients might be correlated with an
      increase in the number of patients with tubulo-interstitial nephritis (TIN). In
      patients with acute TIN, marked fever, back or flank pain, CVA tenderness, skin
      rash, arthralgia, eosinophilia, and eosinouria are observed. Clinical symptoms
      might be induced by glomerular, proximal tubular or distal tubular dysfunction in
      chronic TIN. Mild to moderate proteinuria, edema, hypertension, azotemia,
      glucosuria, aminoaciduria, polyuria and polydipsia are characteristic findings in
      patients with chronic TIN. These findings are slowly progressive in such
      patients. It appears that the marked fibrosis with lymphocyte infiltration in the
      interstitium is a poor clinical marker in patients with TIN. Furthermore, it is
      important to differentiate TIN from glomerulonephritis.

PMID- 7563628
TI  - [Immunological and non-immunological mechanisms of tubulo-interstitial
      nephropathies].
AB  - Studies in experimental models and human cases provide compelling evidence for
      immune mechanisms of tubulo-interstitial nephropathy (TIN) or tubulo-interstitial
      nephritis. Analogous to immune-mediated glomerular injuries, anti-tubular
      basement membrane antibodies, immune complex deposition, antibodies with cell
      surface antigens and cell-mediated reactions may contribute to the initiation and
      progression of TIN. Recent studies further indicate that local expression of
      cytokines, growth factors and adhesion molecules along with activation of tubular
      epithelial cells and fibroblasts participates in the inflammation and
      fibrogenesis in the renal interstitium. This process may also occur secondarily
      to primary glomerulonephritis, in which the tubulo-interstitial injury is
      suggested to be closely associated with the decline in renal function.

PMID- 7563630
TI  - [General examination and renal function test for tubulointerstitial nephropathy].
AB  - This paper deals with the examination of urine and blood specimens and the renal
      function test specifically as they relate to the diagnosis of tubulointerstitial
      nephropathy. The diagnostic significance of urinalysis, measurement of
      creatinine, creatinine clearance, fractional excretion, beta 2-microglobulin,
      alpha 1-microglobulin, N-acetyl-glucosaminidase and free water clearance, the
      Fishberg concentration test and the ammonium chloride loading test is discussed
      in the evaluation of tubulointerstitial disorder. Physicians must choose the most
      appropriate ones among the many examinations and tests also from the viewpoints
      of minimal invasiveness and cost-effectiveness.

PMID- 7563632
TI  - [The image diagnoses on renal diseases; techniques of CT, MRI and ultrasound].
AB  - The accuracy on diagnosing a renal disease greatly depends on what the method is
      used for examination. Among those clinical using radiologic images, the
      techniques of new developed CT, MRI and ultrasonography were discussed. Their
      diagnostic advantages, shortages and the findings on using these techniques to
      detect the renal diseases were also discussed respectively.

PMID- 7563631
TI  - [Renal biopsy for diagnosis of interstitial nephritis].
AB  - Tubulo-interstitial nephropathy or nephritis is suggested if renal function is
      deteriorated and urinary findings are slight. In most cases, the daily urinary
      protein excretion is less than 1 g and macrohematuria is not present. Urinary
      excretion of N- acetyl-beta-glucosaminidase and beta 2-microglobulin is a good
      indicator for tubulo-interstitial damage. Acute renal failure is caused either by
      acute tubulo-interstitial nephritis or acute tubular necrosis. In either case,
      renal biopsy is essential for diagnosis and to characterize the renal damage. In
      the interstitium, edema and fibrosis are seen and lymphocytes, plasma cells,
      polymorpholeukocytes, and/or eosinophils infiltrate. Tubular basement membrane is
      sometimes disrupted and lymphocytes have infiltrated inside (tubulitis).

PMID- 7563633
TI  - [Tubulointerstitial nephropathy--radionuclide imaging diagnosis].
AB  - There are many spectrums in renal diseases which induce tubulointerstitial
      nephropathy (TIN). Primarily, the renal tubule and interstitium are involved but
      glomerular and vascular lesions are found in the chronic course of TIN. Renal
      scintigraphy is poor for evaluating characteristic aspects of tubular function of
      TIN but demonstrate individual renal function as a whole. Particularly,
      measurement of the 99m-Tc-DMSA renal uptake rate is useful for evaluating a
      functioning tubular mass.

PMID- 7563634
TI  - [Acute tubulointerstitial nephritis in acute infection].
AB  - Acute tubulointerstitial nephritis (ATIN) is divided into two groups; acute
      pyelonephritis (APN) and ATIN associated with systemic infections. APN is
      generally occurred in females through the urinary tract. The causative organisms
      are gram-negative enteric bacteria, of which E. coli is the most common. Since
      antibiotics were used for the treatment of the infection, the prognosis became
      favorable, except for the presence of underlying diseases. On the other hand,
      ATIN in systemic infection is characterized by the association of acute renal
      dysfunction and infiltration of the interstitium by inflammatory cells. Renal
      biopsy is needed for adequate diagnosis. Since antibiotic era, the incidence of
      ATIN decreased.

PMID- 7563635
TI  - [Interstitial nephropathy due to chronic bacterial pyelonephritis].
AB  - Chronic renal infection (Chronic bacterial pyelonephritis) is a cause of tubulo
      interstitial nephropathy (nephritis); TIN. The disorder causes end-stage renal
      failure in about 2% of the patients who are treated by dialysis. However, Chronic
      bacterial pyelonephritis is a relatively benign condition that seldom leads to
      renal function loss. The affected kidney shows non-specific histological pictures
      similar to that seen with other diseases producing TIN. Clinical symptoms are of
      ten vague. Obstructive uropathy (eg, stones, benign prostatic hyperplasia) is
      frequently present. The affected kidney, which is almost unilateral, shows
      atrophy and scarring of variable degree. Significant pyuria and bacteriuria may
      or may not be found. Depending on the stage of the disease, the serum creatinine
      and blood urea nitrogen may be normal or elevated. Contributing obstructive
      uropathy should be corrected. The patients must be followed closely, urinary
      tract infection must be controlled and complications (eg, hypertension, azotemia)
      must be identified promptly and treated adequately.

PMID- 7563636
TI  - [Tubulointerstitial nephropathy secondary to collagen-vascular diseases].
AB  - Although collagen-vascular diseases mainly affect glomeruli and vessels,
      tubulointerstitial (TI) involvements as well, are frequently demonstrated
      histologically. In renal biopsy specimens from patients with lupus erythematosus,
      tubular atrophy, mononuclear (MN) cell infiltration into the interstitium and
      interstitial fibrosis are demonstrated in nearly 50% of cases. Immunoglobulins
      and complement components are sometimes deposited along tubular basement
      membrane, suggesting an immune-complex mediated mechanism. Infiltrating cells are
      mainly T cells, but the surface marker studies are not conclusive as to the
      subset of T cells responsible for the inflammation. As for Sjogren syndrome, TI
      changes and renal tubular acidosis are the prominent features of the disease. MN
      cell infiltration in the renal interstitium is also reported in patients with
      systemic vasculitis.

PMID- 7563637
TI  - [Granulomatous tubulointerstitial nephritis--Wegener's granulomatosis,
      sarcoidosis].
AB  - Typical renal histological findings of Wegener's granulomatosis (WG) indicate a
      pauciimmune focal necrotizing glomerulonephritis with periglomerular granuloma
      and marked inflammatory cell infiltration in the interstitium. The recognition of
      the association between C (proteinase-3) anti-neutrophil cytoplasmic antibody (C
      [PR-3] ANCA) and WG is the only tool available to aid in the assessment of
      disease activity. Stage adapted immunosuppressive therapy (glucocorticoids and
      cyclophosphamide) has significantly altered the outcome of this once fatal
      disease. There are four categories of renal disease in Sarcoidosis (SD). 1) renal
      changes by abnormal calcium metabolism, 2) interstitial nephritis or
      granulomatous nephritis, 3) glomerulonephritis and 4) renal vasculitis.
      Corticosteroid therapy yield a favorable outcome for interstitial granulomatous
      nephritis of SD.

PMID- 7563638
TI  - [The renal tubulointerstitium in diabetes mellitus].
AB  - Recently, the tubulo-interstitial lesions in diabetes mellitus (DM) have become
      of greater interest, as well as, glomerulosclerosis. From the view points of
      tubular function, a variety of changes, including tubular proteinuria and
      transport of sodium, glucose, and divalent ions have been known until the present
      time, although the details remain to be elucidated. Morphologically the
      interstitial fibrosis and the thickening of tubular basement membrane were
      pointed out to be important features in incipient or overt diabetic nephropathy
      of insulin-dependent DM patients. We found the expansion of interstitium even in
      the area without hyalinized glomeruli and atrophic tubules in normo- and
      microalbuminuric non-insulin dependent DM patients by semiquantitative evaluation
      of biopsy specimens. Further studies of the mechanisms will be necessary to
      clarify the mechanism of the development of diabetic nephropathy.

PMID- 7563639
TI  - [Renal diseases in disturbance of urate metabolism].
AB  - Although serum concentrations of uric acid could be frequently measured in
      various diseases, most clinicians are less interesting in the significance of
      serum urate levels. Since uric acid is produced in the body and eliminated
      through the kidney into the urine, the kidney plays a main role in controlling
      serum urate level. On the other hand higher concentrations of uric acid in blood
      and urine could involve renal damage because uric acid is less soluble in acidic
      solutions like a tubular fluids, resulting in tubulointerstitial nephropathy. In
      this paper I described that the mechanism of urate metabolism in the human kidney
      and then how disorders of urate metabolism involve the kidney.

PMID- 7563640
TI  - [Nephropathy associated with electrolyte disorders].
AB  - It is well known that renal dysfunction is associated with several types of
      electrolyte disorders. On the other hand, renal manifestations have been
      attributed to electrolyte disorders. Hypokalemia is the most frequent electrolyte
      abnormality encountered in clinical practice. The main cause of hypokalemia is
      due to abuse of laxatives and diuretics or to anorexia nervosa. Hypercalcemia is
      another major electrolyte abnormality, associated with numerous renal
      manifestations. Renal tubules damages and chronic interstitial nephritis are
      characteristic pathological findings in prolonged electrolyte disorders. The
      mechanism of renal involvement and characteristic clinical manifestations of the
      electrolyte disorders are reviewed.

PMID- 7563641
TI  - [Congenital metabolic disorder].
AB  - In children, tubulo-interstitial nephritis (TIN) is often associated with
      obstructive uropathy, metabolic disorders or hereditary diseases. The author
      reviewed congenital metabolic disorders (Fanconi syndrome, cystinosis, Lowe's
      syndrome, and hyperoxaluria) as causes of TIN. The Fanconi syndrome is caused by
      numerous disorders including cystinosis and Lowe's syndrome, and refers to a
      dysfunction of the proximal tubule leading to excessive urinary excretion of
      amino acids, glucose, phosphate, bicarbonate, etc. Prognosis of idiopathic
      Fanconi syndrome is not so bad if electrofluid balance is well maintained. On the
      other hand, prognosis of the infantile type of cystinosis, Lowe's syndrome, or
      hyperoxaluria "type 1" is poor. The pathophysiology of each disease should be
      fully understood for early diagnosis and treatment.

PMID- 7563642
TI  - [Tubulointerstitial changes in some hematological disorders].
AB  - This paper describes tubulointerstitial changes of the kidney in association with
      a) pathophysiology of paraproteinuria and related disorders, and b) the
      management of leukemia and malignant lymphoma. Various forms of
      tubulointerstitial changes might be provoked following the accumulation of
      "abnormal macromolecules" In a), multiple myeloma, light chain cast nephropathy
      (myeloma kidney), AL amyloidosis, light chain deposition disease,
      macroglobulinemia, cryoglobulinemia etc. are briefly reviewed. In the majority of
      cases, leukemia and lymphoma do not manifest themselves as tubulointerstitial
      disorders. However, a large number of patients suffer from tubulointerstitial
      abnormalities in the course of and/or after receiving chemotherapy. Thus it is
      explained, in b), why treatment for hematological malignancy is apt to induce
      tubulointerstitial complications. In this context, drugs responsible for the
      development of tubulitis and/or interstitial fibrosis are briefly reviewed.

PMID- 7563643
TI  - [Cystic disease of the kidney].
AB  - The kidney is one of the most common sites of cyst. Since cystic disease of the
      kidney includes various disorders, it is difficult to classify the diseases
      systematically. It appears that the classification of the American Academy of
      Pediatrics is suitable for clinical side for the present. In this paper the
      cystic disease of the kidney is explained on actual cases. Recently, development
      of imaging diagnosis is contributing widely to the diagnosis of the diseases.
      Treatment of the diseases, however, is not established satisfactorily. It is
      hoped that the mechanism of occurrence of the diseases is known further and that
      regulation of the classification and establishment of the treatment will become
      available.

PMID- 7563644
TI  - [Obstructive and reflux nephropathy].
AB  - Urinary tract obstruction and vesicoureteral reflux have marked effects on renal
      function. Renal interstitial fibrosis and glomerular hypertrophy with subsequent
      focal segmental glomerulosclerosis like changes are a common consequence of
      chronic obstruction and vesicoureteral reflux. Evidence suggests that vasoactive
      compounds and cytokines such as angiotensin II, nitric oxide, eicosanoids, TNF,
      TGF, EGF, PDGF, bFGF have a role in the hemodynamic and structural abnormalities
      that occur following obstruction of the urinary tract or vesicoureteral reflux.
      Use of modulators for these compounds appears to be beneficial for treatment of
      obstructive or reflux nephropathy in near future.

PMID- 7563645
TI  - [Tubulointerstitial damage attributable to acute circulatory failure:
      postischemic acute renal failure].
AB  - Renal damage attributable to acute circulatory failure includes prerenal
      azotemia, postischemic acute renal failure and bilateral renal cortical necrosis.
      In this review, recent findings of the pathophysiology, diagnosis, and treatment
      of postischemic acute renal failure are reviewed. The medullary thick ascending
      limb of Henle and the proximal straight tubule are extremely susceptible to
      ischemic damage because of the characteristic anatomical feature of the vasa
      recta in the medulla. Appropriate supportive treatment and initiation of dialysis
      early in the course of acute renal failure improve survival. However, the
      prognosis of acute renal failure with multiple organ failure is poor. Further
      studies on the precise cellular mechanism of acute renal failure may provide us
      with some future modes of treatment.

PMID- 7563646
TI  - [Renal arterial disease-induced tubulo-interstitial lesions].
AB  - Renal arterial disease-induced tubulo-interstitial lesions described in this
      chapter include benign arterio- and/or arteriolo-sclerotic and malignant
      nephrosclerosis, renal infarction and renal cortical necrosis. In these
      conditions renal glomeruli as well as tubules are always involved, and consequent
      loss of nephrons, or renal parenchyma results in interstitial fibrotic changes.
      The parenchymal lesions have a spectrum from slowly progressive atrophy and loss
      to necrosis of abrupt onset and disappearance of glomeruli and tubules. As for
      glomerular reactions to the ischemia, the intermediate type consisted of
      mesangial degeneration and epithelial cell proliferation described as "alterative
      glomerulitis" is noteworthy. Briefly, in renal arterial diseases, glomeruli are
      rather variably involved than tubules and loss of the parenchyma results in
      interstitial fibrosis.

PMID- 7563647
TI  - [Tubulo-interstitial lesions in human renal allograft].
AB  - Tubulo-interstitial lesions developed in renal allografts are divided to two
      major categories, i.e., primary group specific for renal allografts consisting of
      rejection, cyclosporine nephrotoxicity and post-transplant acute tubular
      necrosis, and secondary group accompanied with nephron atrophy caused by any
      kinds of glomerular, interstitial and/or vascular diseases. An international
      classification for renal allograft biopsy called Banff criteria was proposed and
      a comparative study using this criteria would be possible in any place of the
      world hereafter. After a clinical application of potent immunosuppressive agent
      cyclosporine or taclorimus, acute and chronic rejection related tubulo
      interstitial lesions changed to mild and less specific findings for rejection
      required a new specific diagnostic criteria for chronic rejection. A concomitant
      lesion with rejection, glomerulonephritis and cyclosporine nephrotoxicity was an
      ordinary diagnosis in cyclosporine era. New diagnostic methods using
      immunohistochemistry and electron-microscopy will contribute to a new and
      sophisticated pathologic classification for tubulo-interstitial lesions of renal
      allografts.

PMID- 7563648
TI  - [Clinical aspects of drug-induced tubulo-interstitial nephropathy].
AB  - It is well known that many drugs can induce tubulointerstitial nephropathy (DTIN)
      in the kidney. There are two kinds of onset mechanisms such as dose-dependent and
      allergic nephropathy. Risk factors inducing DTIN are known as aging, dehydration,
      preexisting renal damage, hypertension and serum electrolyte abnormalities.
      Treatment of DTIN is firstly to cease suggestive drugs of inducing nephropathy
      and then followed by diuresis, correcting serum electrolyte levels and sometimes
      hemodialysis or hemoadsorption to reduce the suggested drug levels in the
      circulation. In allergic nephropathy, high-dose glucocorticoid therapy is
      available for improving renal function rapidly. The prevention of DTIN is to know
      the patients background and monitor serum drug levels.

PMID- 7563649
TI  - [Tubulointerstitial injuries in heavy metal intoxications].
AB  - The kidney is one of the organs susceptible to heavy metal intoxication. The
      total body burden and "saturation" level in renal tissue are important limiting
      factors to the onset of renal injuries. Acute or chronic exposure to many of
      heavy metals can induce renal tubulointerstitial injuries, including acute
      tubular necrosis, chronic tubulointerstitial nephritis, Fanconi syndrome, renal
      tubular acidosis, and renal tubular dysfunction without morphological changes.
      Chronic cadmium intoxication can cause irreversible Fanconi syndrome with chronic
      tubulointerstitial nephritis. Both urinary low-molecular weight protein excretion
      and urinary cadmium excretion (greater than 200-400 ppm) are the most reliable
      earlier markers of tubulointerstitial injury in chronic cadmium intoxication. The
      role of metallothionein is central to an understanding of cadmium-induced
      nephropathy. Acute lead intoxication in children can cause reversible Fanconi
      syndrome. Hypertension, hyperuricemia, and elevated serum creatinine, without
      Fanconi syndrome, are clinical manifestations of chronic lead exposure in adults.
      Nuclear inclusion body in proximal tubular cell is characteristic. Chronic
      exposure to inorganic germanium can cause chronic renal failure without urinary
      abnormalities, due to tubular degeneration and interstitial fibrosis, mainly in
      the thick ascending limb of Henle and distal tubulus.

PMID- 7563650
TI  - [Idiopathic chronic tubulointerstitial nephritis].
AB  - Chronic tubulointerstitial nephritis is a chronic disorder that primarily affects
      the renal tubules and interstitium while sparing the glomeruli and vasculature.
      Although there are variable underlying causes, 10% to 25% of the cases of chronic
      tubulointerstitial nephritis are entirely idiopathic. A thorough search for the
      underlying causes of chronic tubulointerstitial nephritis is especially important
      because to avoid or to correct such underlying causes may prevent progression or
      even allow for some reversal of renal failure. Thus, diagnosis of idiopathic form
      of chronic tubulointerstitial nephritis is carefully made after the exclusion of
      potential underlying causes. The major pathologic features of idiopathic chronic
      tubulointerstitial nephritis are 1) interstitial fibrosis, 2) tubular atrophy and
      3) infiltration of the parenchyma with mononuclear inflammatory cells. Of these
      three features, the extent of interstitial fibrosis is significantly correlated
      with decreased glomerular filtration rate and progression rate of renal failure.
      Idiopathic chronic tubulointerstitial nephritis seems to be slowly progressive
      and develop to end stage renal failure. Since there is no specific treatment for
      idiopathic chronic tubulointerstitial nephritis, avoidance and correction of
      exacerbation factors are essential for progression to renal failure. It is
      acceptable that protein-restricted diet be applied to idiopathic chronic
      tubulointerstitial nephritis although its effects on the disease still remain
      equivocal.

PMID- 7563651
TI  - [Hereditary tubulo-interstitial nephropathy].
AB  - Most of the hereditary tubulointerstitial nephropathy see the cyst formation in
      the kidney. Among them, juvenile nephronophthisis and medullary sponge kidney,
      which primarily involve the tubule structures of the renal medulla, are
      associated with variable enlargement of the distal tubules and collecting ducts
      and with interstitial fibrosis and inflammation of a variable extent. Juvenile
      nephronophthisis features sodium wasting, anemia, and renal failure. Eighty % of
      juvenile nephronophthisis is an autosomal recessive disorder, and it also has a
      variant form which is an autosomal dominant disease. A gene for autosomal
      recessive juvenile nephronophthisis is now mapped to 2q13, although no linkage
      has been observed in autosomal dominant variant to this region. Thus genetic
      heterogeneity between autosomal recessive variant and autosomal dominant variant
      of juvenile nephronophthisis is suggested. Juvenile nephronophthisis progress to
      end-stage renal failure. In contrast, medullary sponge kidney, which features
      nephrocalcinosis and urinary stones, is a relatively benign condition and occurs
      occasionally in the same family.

PMID- 7563652
TI  - [Searching for hepatitis C virus by immunoelectron microscopy and its
      morphology].
AB  - Many investigators have searched for the causative agent(s) of blood-borne non-A,
      non-B hepatitis in sera and liver from patients and experimental animals, and
      have reported various virus-like particles, morphologically resembling
      parvovirus, togavirus, picornavirus, hepadnavirus, paramyxovirus, papovavirus,
      retrovirus or bunyavirus. Despite extensive effort, none of these virus-like
      particles has been confirmed universally as an etiologic virus because of the
      absence of immunological identification. The frustration was solved by the
      success in cloning cDNA of the genome of hepatitis C virus (HCV), a major
      etiologic agent of human non-A, non-B hepatitis, in 1989, but the morphology of
      HCV remained in riddles. We attempted to visualize HCV by indirect immunogold
      electron microscopy, using specific antibodies to the putative HCV envelope 1
      protein and succeeded in identifying HCV particle in HCV-RNA-rich plasma. Our
      study showed that HCV particles are 55-65 nm spherical particles with 6 nm fine
      surface spike-like projections, and have a 30-35 nm inner core.

PMID- 7563654
TI  - [HCV envelope gene transgenic mice].

PMID- 7563653
TI  - [Preparation and application of knock-out mice].
AB  - Mouse embryonic stem cells can be cultured in vitro and still retain their
      pluripotency. When reintroduced into mouse embryos, these cells can contribute to
      the germ line of the resultant chimeras. Homologous recombination between DNA
      sequences residing in the chromosome of embryonic stem cells and newly introduced
      DNA sequences allows the transfer of any modification of the cloned gene into the
      genome of a living mouse. This article discusses the current status of knock-out
      mice preparation, with emphasis on unsettled steps, during the knock-out
      procedure and introduces some of the newly developed gene targeting techniques by
      which more ideal animals can be prepared.

PMID- 7563655
TI  - [Role of peptide hormones in adipocyte metabolism].

PMID- 7563656
TI  - [Long term/intermittent treatment of chronic hepatitis C with recombinant
      interferon alfa-2b].

PMID- 7563657
TI  - [Interferon treatment for chronic hepatitis C--assessment of 3 regimens in
      patients received more than 500 MU interferon treatment and their effect
      predictive factors for interferon treatment using multivariate analysis with the
      logistic regression model].

PMID- 7563658
TI  - [Efficacy of interferon re-therapy and its adaptation in chronic hepatitis C].

PMID- 7563659
TI  - [Features and therapy of the patients with chronic hepatitis C resistant to IFN
      therapy].

PMID- 7563660
TI  - [Cationic liposome-mediated expression of hepatitis C virus genome in adult rat
      liver].

PMID- 7563661
TI  - [Efficacy of interferon combined glycyrrhizin therapy in patients with interferon
      resistant chronic hepatitis C].

PMID- 7563662
TI  - [Adverse effect of interferon therapy and its prevention].

PMID- 7563663
TI  - [Role of catecholamines in adipocyte metabolism].

PMID- 7563664
TI  - [HCV gene transfected animal using receptor mediated gene delivery].

PMID- 7563665
TI  - [Ultrastructural feature of HCV particle as revealed by immunoelectron
      microscopy].

PMID- 7563666
TI  - [Role of steroid hormone in adipocyte metabolism].

PMID- 7563667
TI  - [Development of hepatitis C virus vaccine].

PMID- 7563668
TI  - [Proliferation and differentiation of fat cells].

PMID- 7563669
TI  - [An analysis of the B-cell epitopes recognized in hypervariable region 1 of
      hepatitis C virus in chronic persistent hepatitis].

PMID- 7563670
TI  - [Pathogenesis of visceral fat accumulation].

PMID- 7563671
TI  - [Linear B cell epitopes located on core and NS3 regions of HCV].

PMID- 7563672
TI  - [Metabolic steps related to fat accumulation].

PMID- 7563673
TI  - [Viral escape from humoral immune system by mutations in hypervariable region of
      HCV envelope protein and mechanism of persistent viral infection].

PMID- 7563674
TI  - [Regulation of food intake and appetite: overview].

PMID- 7563675
TI  - [Characteristics of adipose].

PMID- 7563676
TI  - [Amino acid substitution of hepatitis C virus for persistent infection].

PMID- 7563677
TI  - [Guidelines for body weight in adults].

PMID- 7563678
TI  - [HCV-RNA in the circulating immune complexes].

PMID- 7563679
TI  - [Indices of obesity derived from body weight and height].

PMID- 7563680
TI  - [Hypervariable region specific formation of immune complexes in a plasma with
      quasispecies of hepatitis C virus].

PMID- 7563681
TI  - [HCV core specific CTL and epitope].

PMID- 7563682
TI  - [Techniques of measurement of human body fat mass: overview].

PMID- 7563683
TI  - [Induction of cytotoxic T cells specific for HCV-NS5 and cytokine].

PMID- 7563684
TI  - [Densitometry (hydrostatic weighing) for measurement of human body fat mass].

PMID- 7563685
TI  - [Structure and organization of hepatitis C virus genome].

PMID- 7563686
TI  - [T cell proliferative responses to HCV-related antigens].

PMID- 7563687
TI  - [Total body water by D2O dilution].

PMID- 7563688
TI  - [Analysis of the mechanisms relating the localization of HCV core protein and
      hepatic injury--an immunohistochemical study].

PMID- 7563689
TI  - [Dual photon absorptiometry, dual energy X-ray absorptiometry for analysis of
      body fat mass].

PMID- 7563690
TI  - [Bio-electrical impedance analysis method for body fat mass].

PMID- 7563691
TI  - [Analyses of cellular immune mechanism in chronic hepatitis C using recombinant
      vaccinia virus expression system].

PMID- 7563692
TI  - [Near infrared interactance for measurement of body fat mass].

PMID- 7563693
TI  - [Significance of apoptosis in hepatitis C and possible involvement of soluble
      factor in hepatocyte apoptosis].

PMID- 7563695
TI  - [Regulatory factors in food intake: overview].

PMID- 7563694
TI  - [Skinfold thickness for analysis of body fat mass].

PMID- 7563696
TI  - [TUNEL method rarely revealed DNA fragmentation in chronic hepatitis C].

PMID- 7563697
TI  - [Evaluation of obesity by anthropometry (weight and height)].

PMID- 7563699
TI  - [Progress in currently available anti-HCV assay systems].

PMID- 7563698
TI  - [Role of Fas system in apoptosis induced by hepatitis C virus infection].

PMID- 7563700
TI  - [Ultrasonic diagnosis of visceral type obesity].

PMID- 7563701
TI  - [The measurement of fat distribution by computed tomography].

PMID- 7563702
TI  - [Immunodominant regions of core protein of hepatitis C virus and antibody-assays
      employing two recombinant core proteins, p22 and JCC4].

PMID- 7563704
TI  - [Waist to hip circumference ratio].

PMID- 7563703
TI  - [Fat measurement using MRI].

PMID- 7563705
TI  - [Serodiagnosis of HCV infection by means of HCV core antibodies (CP-9 Ab, CP-10
      Ab)].

PMID- 7563706
TI  - [Definition, classification and judgement of obesity, and clinical diagnosis of
      obesity as disease].

PMID- 7563708
TI  - [An assay system for ARIMA14 antibody].

PMID- 7563707
TI  - [C8-2 (NS5) antibody and epitope analysis].

PMID- 7563709
TI  - [Etiology of obesity].

PMID- 7563710
TI  - [Anti-GOR antibodies].

PMID- 7563711
TI  - [Quantitative assay of anti-HCV core antibody with JCC-2 ELISA: anti-HCV core IgG
      antibody].

PMID- 7563712
TI  - [Epidemiologic study on factors related to obesity].

PMID- 7563713
TI  - [Mechanism of hepatitis C virus protein processing].

PMID- 7563714
TI  - [Antibodies generated against hepatitis C virus (HCV) core antigen: IgM and IgA
      antibody against HCV core].

PMID- 7563715
TI  - [Visceral fat obesity].

PMID- 7563716
TI  - [Regulatory factors in food intake: glucoreceptor neuron and gluco-sensitive
      neuron].

PMID- 7563717
TI  - [Specific antibody assay for genotyping of hepatitis C virus].

PMID- 7563718
TI  - [Obesity as a risk factor of diabetes mellitus (prospective study)].

PMID- 7563719
TI  - [Relationship between ELISA-based serotypic grouping and PCR-based genotypic
      grouping of HCV].

PMID- 7563720
TI  - [Obesity as a risk factor of hypertension (prospective study)].

PMID- 7563721
TI  - [Serotypes of hepatitis C virus defined by antibodies directed to the putative
      core protein].

PMID- 7563722
TI  - [Detection of hepatitis C virus RNA with reverse transcription-nested polymerase
      chain reaction].

PMID- 7563723
TI  - [Obesity as a risk factor of ischemic brain disease (prospective study].

PMID- 7563724
TI  - [The relationship between the incidence of ischemic heart disease and the degree
      of obesity].

PMID- 7563725
TI  - [Quantitation of HCV-RNA by competitive-PCR].

PMID- 7563727
TI  - [Serum levels of HCV-RNA determined by branched DNA (bDNA) probe assay in chronic
      hepatitis C].

PMID- 7563726
TI  - [Obesity as a risk factor of breast cancer (prospective study)].

PMID- 7563728
TI  - [Obesity as a risk factor of endometrial cancer of the uterus].

PMID- 7563729
TI  - [Method of detecting plus and minus strands of hepatitis C viral RNA by strand
      specific reverse transcription-polymerase chain reaction].

PMID- 7563730
TI  - [Abnormal glucose metabolism and insulin resistance in obesity].

PMID- 7563731
TI  - [Nervous regulation of metabolism].

PMID- 7563732
TI  - [Expression and purification of hepatitis C virus serine proteinase].

PMID- 7563733
TI  - [Detection of HCV-RNA in liver by in situ hybridization].

PMID- 7563734
TI  - [Obesity and hyperlipidemia].

PMID- 7563735
TI  - [Detection of hepatitis C virus (HCV) infected cell using in situ hybridization
      and PCR in situ hybridization].

PMID- 7563736
TI  - [Hyperuric acidemia and obesity].

PMID- 7563737
TI  - [PCR-based genotyping with genotype-specific primers derived from the C gene of
      HCV genome].

PMID- 7563738
TI  - [Endocrine function (pituitary, thyroid, adrenal gland) of obesity].

PMID- 7563739
TI  - [Effect of obesity on gonadal function in men].

PMID- 7563740
TI  - [Genotyping of hepatitis C virus by polymerase chain reaction with a mixed primer
      set derived from nucleotide sequences of NS5 region].

PMID- 7563741
TI  - [Hemodynamics in obesity].

PMID- 7563742
TI  - [Prediction of interferon therapy outcome by PCR-SSCP analysis of HCV 5' NCR].

PMID- 7563743
TI  - [Role of biogenic amines (catecholamines, histamine, serotonin, etc.) in food
      intake].

PMID- 7563744
TI  - [Cardiac hypertrophy and ischemic heart disease in obesity].

PMID- 7563745
TI  - [Sequencing of HCV genome by using RT-PCR products].

PMID- 7563746
TI  - [Cerebral circulatory disorder, ischemic cerebrovascular disease in obesity].

PMID- 7563747
TI  - [Analysis of hepatitis C virus quasispecies populations using PCR-SSCP method].

PMID- 7563748
TI  - [Respiratory function disturbance in obesity].

PMID- 7563749
TI  - [Epidemiology of hepatitis C virus infection in Japan].

PMID- 7563751
TI  - [Long-term prognosis in patients with epidemic hepatitis C].

PMID- 7563750
TI  - [Diseases of the biliary system in obesity].

PMID- 7563752
TI  - [Liver injuries in obese patients].

PMID- 7563753
TI  - [Molecular epidemiology of HCV in hyperendemic area].

PMID- 7563754
TI  - [Renal alterations in obesity].

PMID- 7563755
TI  - [Structural and functional analysis of the internal ribosome entry site within 5'
      noncoding region of hepatitis C virus RNA].

PMID- 7563756
TI  - [Present status of hepatitis C virus infection and molecular evolutionary
      analysis in the area with frequent occurrence of hepatitis C].

PMID- 7563757
TI  - [Abnormality of coagulation and fibrinolysis in obesity].

PMID- 7563758
TI  - [Prevalence and transmission of hepatitis C virus in polluted area in Japan].

PMID- 7563759
TI  - [Obesity associated with distorted function of autonomic nervous system].

PMID- 7563760
TI  - [Molecular epidemiology of infection by hepatitis C virus in the Airin District
      of Osaka City].

PMID- 7563763
TI  - [Orthopaedic disorders and problems related to obesity].

PMID- 7563762
TI  - [Etiologic and clinical studies of hepatitis C in an epidemic area in Japan].

PMID- 7563761
TI  - [Impaired immunity in obesity].

PMID- 7563764
TI  - [The recent incidence of post-transfusion hepatitis C since the implementation of
      the anti-HCV screening program for blood donors].

PMID- 7563765
TI  - [Gynecological diseases in obesity].

PMID- 7563766
TI  - [A follow up study of patients who received blood positive for hepatitis C virus
      core antibody, with genetic evidence of hepatitis C virus transmission].

PMID- 7563767
TI  - [Mental disorders and obesity].

PMID- 7563768
TI  - [HCV screening of blood donors and its preventive effect on PT-HC].

PMID- 7563769
TI  - [Feeding behavior: its deviation in obese subjects].

PMID- 7563771
TI  - [Transfusion associated HCV infection].

PMID- 7563770
TI  - [Effect of gut peptides on feeding and body weight regulation].

PMID- 7563772
TI  - [Features of eating behaviour and their psychological background in simple
      obesity patients].

PMID- 7563773
TI  - [Mother-to-infant transmission of HCV].

PMID- 7563774
TI  - [HCV-RNA and HCV genotype in mother-to-infant transmission of HCV].

PMID- 7563775
TI  - [Obesity due to central nervous system diseases].

PMID- 7563777
TI  - [Endocrine obesity].

PMID- 7563776
TI  - [Mother to child transmission of HCV--from the analysis of the nucleotide
      sequence].

PMID- 7563778
TI  - [Intrafamilial transmission of hepatitis C].

PMID- 7563779
TI  - [Drug induced obesity].

PMID- 7563780
TI  - [Analysis of intrafamilial and spouse to spouse transmission of hepatitis C virus
      by molecular evolutionary method].

PMID- 7563781
TI  - [Highly conserved secondary structures predicted in 5' noncoding region of HCV: a
      possible connection to viral replication].

PMID- 7563782
TI  - [Obesity due to alcohol intake].

PMID- 7563784
TI  - [Genetic syndrome with obesity].

PMID- 7563783
TI  - [Infection and prevention of hepatitis C virus in medical personnel].

PMID- 7563785
TI  - [General aspects of the management for obesity].

PMID- 7563787
TI  - [Investigation into hepatitis C virus infection after needlestick injury].

PMID- 7563786
TI  - [Diet therapy in obesity].

PMID- 7563788
TI  - [Physical exercise and obesity].

PMID- 7563789
TI  - [Prevalence of hepatitis C virus infection among chronic hemodialysis patients].

PMID- 7563790
TI  - [Behavioural modification for therapy of obesity].

PMID- 7563791
TI  - [HCV infection in Japanese hemophiliacs].

PMID- 7563792
TI  - [Drug abuse and HCV infection].

PMID- 7563793
TI  - [Tattooing as a risk factor of HCV infection].

PMID- 7563795
TI  - [Hepatitis C virus infection as sexually transmitted diseases].

PMID- 7563796
TI  - [Psychotherapy for obesity].

PMID- 7563794
TI  - [Cognitive-behavioral therapy for obesity--with special reference to binge eating
      disorder].

PMID- 7563797
TI  - [Demonstration of hepatitis C virus genome in saliva and urine of patients with
      type C hepatitis].

PMID- 7563798
TI  - [Drug treatment of obesity].

PMID- 7563799
TI  - [Detection of HCV-RNA in saliva and stool of patients with HCV infection].

PMID- 7563800
TI  - [Surgical treatment of morbid obesity].

PMID- 7563801
TI  - [General remarks of acute hepatitis C].

PMID- 7563802
TI  - [Effect of brain peptides on feeding and body weight regulation].

PMID- 7563803
TI  - [Early diagnosis of acute hepatitis C and usefulness of IgM anti-HCV for its
      diagnosis].

PMID- 7563805
TI  - [Sequential analysis of the hypervariable region of the hepatitis C virus genome
      in acute infection].

PMID- 7563804
TI  - [Very low calorie diets for obesity].

PMID- 7563807
TI  - [Evolutionary analysis of the hypervariable region of hepatitis C virus E2/NS1
      gene in the case infected by a needlestick accident].

PMID- 7563806
TI  - [Effects of one-week inpatient weight reduction program for obese persons].

PMID- 7563810
TI  - [Morbid obesity].

PMID- 7563808
TI  - [Processing of hepatitis C virus envelope proteins].

PMID- 7563809
TI  - [Post-transfusion hepatitis C, its diagnosis and treatment].

PMID- 7563812
TI  - [Diagnosis of childhood obesity].

PMID- 7563811
TI  - [Studies on predictive factors of prolonged cases in type C acute sporadic
      hepatitis--serial analysis of transaminase and anti-HCV markers].

PMID- 7563813
TI  - [Interferon therapy for acute hepatitis C: evaluation by HCV antibody, HCV
      genotypes and serum RNA titer].

PMID- 7563814
TI  - [Complication of childhood obesity].

PMID- 7563815
TI  - [The role of hepatitis C virus in fulminant hepatitis].

PMID- 7563816
TI  - [Childhood obesity: treatment and prognosis].

PMID- 7563817
TI  - [Clinical and immuno-virological aspects in type C fulminant hepatitis].

PMID- 7563818
TI  - [Obesity in the elderly].

PMID- 7563819
TI  - [Pathology of type C fulminant hepatitis and type C subacute hepatitis].

PMID- 7563820
TI  - [Operative complications of obese patients and its countermeasure].

PMID- 7563821
TI  - [Virological and immunological pathogenesis of hepatitis C virus-associated
      fulminant and subacute hepatitis].

PMID- 7563822
TI  - [Treatment of type C fulminant and subfulminant hepatitis--featuring antiviral
      and immunosuppressive treatment].

PMID- 7563823
TI  - [Obesity in pregnancy and delivery].

PMID- 7563827
TI  - [The virological and histological states of anti-HCV-positive subjects with
      normal liver biochemical values].

PMID- 7563826
TI  - [Clinicopathological studies on the solitary positive cases of HCV core
      antibody].

PMID- 7563825
TI  - [Bulimia nervosa and obesity].

PMID- 7563824
TI  - [Clinico-pathological study of so-called asymptomatic HCV carrier].

PMID- 7563829
TI  - [Molecular evolutionary analysis of hepatitis C virus--phylogenetic tree and
      divergence time].

PMID- 7563830
TI  - [Comparison of hepatohistological findings with asymptomatic HCV carrier and
      asymptomatic HBV carrier].

PMID- 7563828
TI  - [Molecular biology of obesity].

PMID- 7563832
TI  - [Obesity and syndrome X].

PMID- 7563831
TI  - [Histological features and HLA-DNA types in HCV carriers with persistently normal
      ALT levels].

PMID- 7563834
TI  - [An introduction to chronic hepatitis C].

PMID- 7563833
TI  - [Role of cytokines in regulation of food intake and appetite].

PMID- 7563835
TI  - [Progress in research on the central mechanism of feeding behavior--neuronal
      network].

PMID- 7563836
TI  - [Fundamentals of chronic viral hepatitis and histopathological characteristics of
      chronic hepatitis C].

PMID- 7563837
TI  - ["The FIND" classification for assessing histological staging and activity in
      chronic viral hepatitis].

PMID- 7563838
TI  - [Experimental animal models of obesity].

PMID- 7563840
TI  - [Histological activity index score and levels of hepatitis C virus RNA in chronic
      hepatitis C].

PMID- 7563839
TI  - [Classification of chronic hepatitis (staging) and serum HCV-RNA levels].

PMID- 7563841
TI  - [Relation between histological findings by Scheuer's scores and serum levels of
      HCV-RNA, and HCV-genotype].

PMID- 7563842
TI  - [Hepatitis C viral quasispecies in patients with type C chronic liver disease].

PMID- 7563843
TI  - [Distribution of HCV-infected hepatocytes in chronic hepatitis C].

PMID- 7563844
TI  - [HCV-RNA in liver of chronic hepatitis C--plus strand RNA and minus strand RNA].

PMID- 7563845
TI  - [Cytokine gene expression in the liver of chronic hepatitis C].

PMID- 7563846
TI  - [An immunohistochemical analysis in portal lymphocytic aggregation of chronic
      hepatitis C].

PMID- 7563847
TI  - [Genetic heterogeneity and variability of hepatitis C virus and hypervariable
      regions].

PMID- 7563848
TI  - [Role of growth factors in regulation of food intake].

PMID- 7563849
TI  - [Analyses of T-cell receptor repertoire in liver-infiltrating lymphocytes in
      chronic hepatitis C using immunohistochemical and PCR methods].

PMID- 7563850
TI  - [The prognosis of chronic hepatitis C--comparison between patients with genotypes
      1 and 2 hepatitis C viruses].

PMID- 7563851
TI  - [Hepatic and extrahepatic HCV-RNA strands of patients infected with hepatitis C
      virus].

PMID- 7563852
TI  - [Nucleotide sequence substitutions of hepatitis C virus].

PMID- 7563853
TI  - [Histological findings of the liver].

PMID- 7563855
TI  - [Long-term prognosis of the interferon-treated patients with chronic hepatitis
      C].

PMID- 7563856
TI  - [Long-term follow up of histological changes in IFN-treated patients with chronic
      hepatitis C].

PMID- 7563854
TI  - [Immunohistochemical observation of Fas in the liver with chronic hepatitis C].

PMID- 7563857
TI  - [The etiology of liver cirrhosis and the clinical analysis of anti-HCV positive
      patients with liver cirrhosis].

PMID- 7563858
TI  - [Causative incidence of hepatic cirrhosis and clinical statistics of hepatic
      cirrhosis type C].

PMID- 7563860
TI  - [Causes of liver cirrhosis and clinical statistics on HCV associated liver
      cirrhosis].

PMID- 7563859
TI  - [Steroid hormone receptors in the CNS from animal models with fatty syndrome].

PMID- 7563861
TI  - [Classification of hepatitis C virus genotypes and its application to molecular
      epidemiology].

PMID- 7563862
TI  - [Clinical course and prognostic value of Child-Turcotte criteria and Child-Pugh
      score in medically treated cirrhosis positive for HCV antibody--in comparison
      with cirrhosis positive for HBs Ag].

PMID- 7563863
TI  - [Progress of chronic hepatitis C to liver cirrhosis--comparison with chronic
      hepatitis B].

PMID- 7563864
TI  - [Risk factors for development of hepatocellular carcinoma in patients with liver
      cirrhosis associated with hepatitis C virus].

PMID- 7563865
TI  - [Influence of heavy drinking for the development of hepatocellular carcinoma in
      type C cirrhosis].

PMID- 7563866
TI  - [High risk group for evolution of hepatocellular carcinoma from HCV related liver
      cirrhosis].

PMID- 7563867
TI  - [Significance of hepatocellular proliferation in the development of
      hepatocellular carcinoma from anti-hepatitis C virus-positive cirrhotic
      patients].

PMID- 7563868
TI  - [Possibility and significance of interferon therapy for liver cirrhosis type C].

PMID- 7563870
TI  - [Does interferon therapy on type C liver cirrhosis prevent the occurrence of
      hepatocellular carcinoma?].

PMID- 7563871
TI  - [Epidemiology of hepatocellular carcinoma and hepatitis C virus in Japan].

PMID- 7563869
TI  - [Role of activin and inhibin in regulation of food intake].

PMID- 7563872
TI  - [Clinical features of hepatitis C virus-related liver cancer].

PMID- 7563874
TI  - [HCV genome in type C hepatocellular carcinoma].

PMID- 7563873
TI  - [The clinical difference of HCV-related hepatocellular carcinoma and HBV-related
      hepatocellular carcinoma].

PMID- 7563875
TI  - [Hepatitis C virus infection in Japanese patients with hepatocellular carcinoma-
      an analysis by direct detection of HCV-RNA in paraffin-embedded specimens].

PMID- 7563877
TI  - [Analysis of replicating hepatitis C virus quasispecies in hepatocellular
      carcinoma tissues using PCR-SSCP method].

PMID- 7563876
TI  - [Comparison of hepatocellular carcinoma type C and B by quantitation of serum HCV
      RNA and HBV-DNA using branched DNA probe assay].

PMID- 7563879
TI  - [A comparative study of hypervariable regions in positive- and negative-stranded
      HCV-RNAs from hepatocellular carcinoma and the surrounding liver].

PMID- 7563878
TI  - [Expression of HCV proteins by using recombinant baculoviruses].

PMID- 7563881
TI  - [Recurrence and prognosis of hepatitis C virus-related hepatocellular carcinoma-
      as compared with hepatitis B virus-related cases].

PMID- 7563882
TI  - [Recurrence rates and prognosis after hepatectomy on the patients with
      hepatocellular carcinoma compromised with HCV hepatitis--comparison between B, BC
      and NBNC type].

PMID- 7563880
TI  - [Incidence of hepatocellular carcinoma in patients treated with interferon].

PMID- 7563883
TI  - [Radical and multimodality therapy for hepatitis C virus-related hepatocellular
      carcinoma].

PMID- 7563884
TI  - [Natural course of infants with hepatitis C virus].

PMID- 7563885
TI  - [A clinical and pathological features of children with hepatitis C virus
      infection].

PMID- 7563886
TI  - [Treatment of children with chronic hepatitis C with IFN].

PMID- 7563887
TI  - [Diagnosis of alcoholic liver disease with HCV].

PMID- 7563888
TI  - [Role of miscellaneous substances (organic acids, lactone, etc) in regulation of
      food intake].

PMID- 7563889
TI  - [Expression of the proteins encoded by the hepatitis C viral genome by vaccinia
      virus expression system].

PMID- 7563890
TI  - [Hepatitis C virus infection in alcoholic patients with chronic liver disease].

PMID- 7563891
TI  - [Histopathological characteristics of alcoholic liver injury in cases with serum
      HCV markers].

PMID- 7563892
TI  - [Treatment for alcoholic liver disease with HCV].

PMID- 7563893
TI  - [HCV infection in autoimmune hepatitis].

PMID- 7563894
TI  - [Clinical manifestation and immunogenetic background of HCV-marker-positive
      autoimmune hepatitis].

PMID- 7563895
TI  - [Molecular mimicry between LKM 1-autoantigen and HCV-polyproteins].

PMID- 7563896
TI  - [Selection of therapy for chronic hepatitis C with feature of autoimmune
      hepatitis].

PMID- 7563897
TI  - [Analysis of the frequency of superinfection with hepatitis C virus in chronic
      hepatitis B virus carriers].

PMID- 7563898
TI  - [Clinical characteristics of HBV and HCV coinfection in patients with chronic
      hepatitis].

PMID- 7563899
TI  - [Superinfection of HCV in HBV carrier and its histological progress of liver
      disease].

PMID- 7563900
TI  - [Human interferon: molecular mechanisms of antiviral activities].

PMID- 7563901
TI  - [Expression of HCV genes using adenovirus vector with CAG promoter].

PMID- 7563902
TI  - [Genomic changes in the E2/NS1 region of HCV before and after IFN therapy].

PMID- 7563903
TI  - [Molecular biology of adipocyte metabolism and obese gene].

PMID- 7563905
TI  - [Different effect of interferon on hepatitis C virus genomes using CAT expression
      system].

PMID- 7563904
TI  - [Fluctuation of hepatitis C virus quasispecies with interferon treatment and
      interferon-resistant variants in hepatitis C virus 1b].

PMID- 7563906
TI  - [HCV-RNA of the hepatocytes of the complete responders with disappearance serum
      HCV-RNA after IFN treatment--using in situ hybridization].

PMID- 7563907
TI  - [Clinical evaluation of positive- and negative-stranded HCV-RNAs in liver in
      relation to IFN therapy].

PMID- 7563908
TI  - [Hypermethylation and inactivity of hepatitis C virus cDNA transgene in
      transgenic mice].

PMID- 7563909
TI  - [HCV genotype as a predictor of response to IFN therapy in chronic hepatitis C].

PMID- 7563910
TI  - [HCV-serotype and IFN response].

PMID- 7563911
TI  - [HCV-RNA quantity of the serum].

PMID- 7563912
TI  - [Change of HCV-RNA levels in liver tissue and interferon responsiveness in
      patients with chronic hepatitis C].

PMID- 7563914
TI  - [Changes of serum 2',5'-oligoadenylate synthetase activity and neopterin during
      interferon treatment for chronic hepatitis C].

PMID- 7563913
TI  - [Liver histology as a predictor of the response to interferon therapy].

PMID- 7563915
TI  - [Criteria of IFN treatment for chronic hepatitis C].

PMID- 7563916
TI  - [Treatment of chronic hepatitis C with different regimens of interferon].

PMID- 7563917
TI  - [Therapeutic effects of interferon on chronic hepatitis C from the aspect of
      dosage and method of administration].

PMID- 7563918
TI  - [Endoscopic mucosal resection of the stomach using a ligating device (EMRL)-
      experimental study for the purpose of establishing reliable and safe technique].
AB  - We confirmed a new reliable and safe technique for endoscopic mucosal resection
      of the stomach using a ligating device (EMRL), which was used for endoscopic
      ligation of esophageal varices. We resected the gastric mucosa by this procedure
      in 6 mongrel dogs, and examined resected specimens histopathologically. It is
      concluded that EMRL can take a mucosal specimen 15 x 12mm in size on the average,
      be performed almost all the site which was previously difficult to resect
      endoscopically, and the submucosal local injection of physiological saline
      solution is necessary to perform EMRL. Based on these conclusion, we experimented
      to establish the safe and reliable technique of the divided mucosal resection,
      too. EMRL procedure is an easy and valuable treatment modality.

PMID- 7563919
TI  - [Study of gastric mucosal lesion in portal hypertension].
AB  - An assessment has been made regarding the gastric mucosal lesion associated with
      portal hypertension clinically and histopathologically. Endoscopically,
      characteristic findings were those accompanied mainly by mucosal atrophy, red
      spots and hemorrhagic spots (portal hypertensive gastropathy: PHG). It was
      considered that rupture of the gastric mucosal defense factor is involved in
      portal hypertension as gastric acid secretion shows hypoacidity in the patients.
      The true form of portal hypertension is considered to be congestive gastropathy
      from the points that PHG is observed in high frequencies in the high portal
      pressure group, the severe esophageal varices group and group without gastrorenal
      or splenorenal shunt, that the mucosal blood flow rate in the lesion increased
      and that venectasia is present in the submucosal layer. Exacerbation of PHG was
      observed in the fundic area after EIS (endoscopic injection sclerotherapy), but
      no particularly large change was observed in the region after direct operation on
      esophageal varices. Administration of propranolol was effective for PHG.

PMID- 7563920
TI  - [Effects of medical vagotomy and sympathectomy on gastric mucosal prostaglandins
      in water immersion restrain rats].
AB  - Ulcer index (UI), gastric submucosal blood flow (SMBF), gastric fundic mucosal
      content of 5 prostaglandins (PGE2, TXB2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha)
      were measured in water immersion restrain rats under medical vagotomy (MV) or
      medical sympathectomy (MSp). UI decreased under MV and MSp with 6 hours stress.
      SMBF decreased less under MV and MSp than control rats. PGE2 of control rats
      decreased under stress, but increased under MV and MSp. It is resulted that MV
      and MSp effect PGE2 to increase, inhibition of SMBF decreasing because of
      increasing PGE2 were recognised and there for stress ulcer were inhibited.

PMID- 7563921
TI  - [Blood coagulation and fibrinolysis in relation to endotoxemia in liver cirrhosis
      and hepatocellular carcinoma].
AB  - The blood coagulation and fibrinolysis of 33 patients with compensated liver
      cirrhosis and 31 patients with hepatocellular carcinoma were examined using
      several markers, namely thrombin-antithrombin III complex (TAT), plasmin-alpha 2
      plasmin inhibitor complex (PIC), antithrombin-III (AT-III) and prothrombin time,
      and the relationship between these markers, endotoxemia, and TNF-alpha was
      examined. These patients had no complications due to hepatic failure, such as
      infections, encephalopathy, ascites, G-I bleeding and clinical DIC. PIC was not
      elevated, but TAT tended to be elevated in LC and significantly elevated in HCC.
      AT-III was decreased in LC and HCC, and the blood endotoxin was partly positive
      in LC and HCC, but was not correlated with AT-III or PT. The TAT level in the
      blood-endotoxin-positive patients measured by endospecy methods was higher than
      that in the negative patients, and was significantly correlated with the blood
      endotoxin level in the LC and HCC patients (r = 0.57, r = 0.88, p < 0.01). No
      relationship was observed between TNF-alpha and blood endotoxin. In conclusion,
      (1) blood coagulability was activated already in compensated LC and HCC, but was
      not connected with fibrinolysis, (2) the activation of coagulability was closely
      related with endotoxemia, and (3) TNF-alpha was not correlated with blood
      endotoxin or TAT.

PMID- 7563922
TI  - [Morphological analysis of the gallbladder elevated lesions--Macroscopic,
      stereoscopic, and histological study].
AB  - I analyzed morphological pathology of elevated lesions of gallbladder (ELGB) 136
      cases, 177 lesions. According to the characteristic morphological feature, I can
      reach to differential diagnosis of ELGB. Most of I s and II a type carcinoma is
      papillary adenocarcinoma, which have irregular papillary surface. A few of II a
      type carcinoma is tubular adenocarcinoma, which is macroscopically granular and
      nodular, but, have stereoscopically small, uneven pits. Adenoma, most of which is
      tubular adenoma, is pedunculated, and have macroscopically multinodular,
      stereoscopically smooth surface. Whereas, hyperplastic polyp can be classified to
      "papillary type" and "nodular type", according to surface structure. "Papillary
      type" is pedunculated or sessile, but, "nodular type" is only sessile. This
      morphological feature is different from adenoma's. Pedunculated carcinoma (I p
      type) is frequently localized in mucosa. Whereas, if we can exclude
      adenomyomatosis, sessile lesion, more than 13mm is frequently advanced carcinoma,
      which invade to subserosa or more deeply. But, sessile carcinoma, smaller than
      11mm, is frequently early carcinoma, which is localized in mucosa or muscle
      layer.

PMID- 7563923
TI  - [Localization of NADPH-diaphorase activity and NOS immunoreactivity in the
      pancreas of rat and dog].
AB  - To clarify the role of nitric oxide (NO) in the pancreas, we investigate the
      localization of NADPH-diaphorase activity and neuronal nitric oxide synthase
      (nNOS) immunoreactivity in the pancreas of the rat and dog. NADPH-diaphorase
      activity and nNOS immunoreactivity were identical in the neuronal element of both
      species. NADPH-diaphorase activity and nNOS immunoreactivity were localized in
      neurons and endothelial cells of vascular system. Numerous NADPH-diaphorase
      positive and nNOS immunoreactive fibers were observed around pancreatic ducts and
      arteries. A moderate number of NADPH-diaphorase positive and nNOS immunoreactive
      fibers were observed surrounding the acini of dog pancreas, but there were few of
      these structures in rat pancreas. The islets of the rat pancreas contained a
      moderate number of NADPH-diaphorase positive and nNOS immunoreactive fibers.
      However in the dog, these positive fibers were not detected inside the islets. In
      the rat pancreas, 85% of the ganglion cells showed NADPH-diaphorase staining. In
      the dog, however, 30-50% of the ganglion cells demonstrated NADPH-diaphorase
      activity. Although NADPH-diaphorase histochemistry did not show any positive
      staining in the islet cells of pancreas in either species, NOS immunocytochemical
      method demonstrated weak positive staining in the rat islet cells. These results
      indicate that NO may play an important role for the neuronal regulation of
      pancreatic exocrine and endocrine activities in both species, but in the species
      specific manner.

PMID- 7563924
TI  - [An analysis on fat digestion in the upper small intestine after intragastric
      infusion of a test meal in patients with exocrine pancreatic insufficiency].
AB  - To clarify the mechanism of the fat maldigestion in 9 patients with exocrine
      pancreatic insufficiency, lipase activities, pH, and micellar lipids in the upper
      small intestinal contents were studied. The upper small intestinal pH was
      slightly less in patients with exocrine pancreatic insufficiency than in healthy
      controls. Lipase activities and micellar lipids were significantly reduced in
      patients with exocrine pancreatic insufficiency compared with in healthy
      controls. There was a significant correlation between serum cholesterol and
      micellar cholesterol concentrations. The results suggest that there is
      maldigestive state in the digestion-absorption process in patients with exocrine
      pancreatic insufficiency due to insufficiency of lipase secretion and that
      insufficiency of lipase secretion disturbs hydrolysis of triglyceride and
      prevents micelle formation and leads to reduced uptake of cholesterol into
      micellar phase and it is reflected in serum cholesterol.

PMID- 7563925
TI  - [A case of giant gastric varices successfully treated by arranged balloon
      occluded retrograde transvenous obliteration].

PMID- 7563926
TI  - [A case of eosinophilic gastroenteritis accompanied by perimyocarditis, which was
      strongly suspected].

PMID- 7563927
TI  - [A case of duodenal Brunner's gland hyperplasia associated with in situ
      carcinoma].

PMID- 7563928
TI  - [A case of adult human herpesvirus-6 associated hemophagocytic syndrome recovered
      from acute liver failure].

PMID- 7563929
TI  - [Two cases of acute exacerbation of chronic hepatitis C improved after the
      administration of an immunosuppressive drug and interferon].

PMID- 7563930
TI  - [A case of insulinoma whose secretion of insulin was inexplicably low].

PMID- 7563931
TI  - [A case of intrapancreatic accessory spleen with epidermoid cyst].

PMID- 7563932
TI  - [A case report of the VIP producing tumor with liver metastasis presenting WDHA
      syndrome].

PMID- 7563933
TI  - [Carcinoma of the large intestine among the aged Japanese].

PMID- 7563934
TI  - [Reliability and validity of a Japanese version of the cost of care index].
AB  - The home management of chronic disability in the elderly often relies upon the
      receipt of family. These caregivers have been shown to experience a considerable
      burden in providing day-to-day care. It is important that identifying problem
      areas may result in the need of consider alternatives for the care of an elderly
      person, identify and mobilize existing community resources to relieve some of the
      "cost". We studied the reliability and validity of a Japanese version of the Cost
      of Care Index (CCI) which was originally developed by Kosberg et al as a case
      management tool in the assessment of caregivers. Our subject consisted of 27
      cases with dementia (mean age 74.5 years), and 15 cases of patients with
      neurological disorders without dementia (80.7 years), and their caregivers. The
      test-retest reliability and internal consistency were very good; the coefficient
      of correlation between CCI scores at the two interviews was 0.83, the coefficient
      of internal consistency was 0.92. CCI scores correlated significantly with ADL-20
      scores, DBD score and caregivers' SDS scores; r = -0.48, r = 0.46 and r = 0.36,
      respectively. Our results indicate that the CCI is highly reliable, and may be
      useful for assessment caregivers' burden.

PMID- 7563935
TI  - [Usefulness of COP-BLAM therapy with concomitant G-CSF in elderly patients with
      non-Hodgkin's lymphoma in comparison with patients not given G-CSF].
AB  - COP-BLAM therapy with concomitant G-CSF was performed in patients 65 years of age
      of older with non-Hodgkin's lymphoma (NHL) and the therapeutic effects and its
      adverse effects were compared with those in a group not given G-CSF
      concomitantly. The subjects were 64 patients with NHL, divided into 36 in the G
      CSF group and 28 in the non-G-CSF group. In the G-CSF group, complete remission
      (CR) was achieved in 88.9% and the efficacy rate was 94.5%. In the non-G-CSF
      group, 89.3% achieved CR, and there was no significant difference between the G
      CSF and non-G-CSF groups. The survival time and duration of remission also showed
      no significant differences between the G-CSF and non-G-CSF groups. The frequency
      of granulocytopenia as an adverse effects was significantly reduced in the G-CSF
      group, but the other adverse effects showed no intergroup differences. The
      occurrence rates of fever of at least 37.5 degrees C and documented infection
      were significantly less in the G-CSF group. These results indicate that COP-BLAM
      therapy with concomitant G-CSF achieved a high remission rate, showed few severe
      adverse effects, especially infections, and can be safely performed in elderly
      patients.

PMID- 7563936
TI  - [Chronological study concerning ADL among Okinawan centenarians].
AB  - Since 1976 medicobiological and sociological surveys have been carried out upon
      centenarians in Okinawa. Recently dementia and disability have increased among
      centenarians. In order to determine the statistical significance, ADL (Activities
      of Daily Living) scores among Okinawan centenarians were compared; 43 subjects
      were studied from the 1970's (1976-1980), 99 subjects from the 1980's (1986
      1988), and 109 subjects from the 1990's (1992-1994). ADL scores of each
      centenarian were recorded by the same researchers at the University of the
      Ryukyus Hospital, based on observation and examination of the centenarians where
      they lived. Five categories of self sufficiency were defined; completely
      independent, independent but slow, independent with difficulty, partially
      dependent, and completely dependent. There were seven physical tasks scored;
      taking meals, bowel and bladder continence, ability to rise from a toilet,
      ability to stand, extent of general activities, ability to bathe, and ability to
      dress oneself. Their sensory functions (auditory acuity and eyesight) and
      cognitive abilities (comprehension and self-expression) were also scored.
      Declining rates of total ADL scores were more marked between the 1970's and the
      1980's than between the 1980's and the early 1990's. It was also more remarkable
      in institutionalized centenarians than in centenarians living at home. Decline in
      physical activities was more distinct in institutionalized than in home-living
      centenarians. On the other hand, cognitive abilities declined more among
      centenarian living at home than among institutionalized centenarians. The
      population of centenarians has increased 23 times over the past 22 years in
      Okinawa. Human life span has been remarkably extended by advanced medical
      technology, physically easier life style, and improvement in overall social
      welfare.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563937
TI  - [Gastric cancer in the elderly].
AB  - Gastric cancer in the elderly was evaluated with regard to age-related
      pathomorphological changes. Resected gastric cancer was studied with regard to
      location, stage, morphology and histology in male young old (65-74 years old)
      which were 25 cases and 31 lesions, respectively male middle old (75-84 years
      old); 104 cases and 120 lesions, male very old (85 years-); 96 cases and 110
      lesions, female young old; 22 cases and 31 lesions, female middle old; 91 cases
      and 106 lesions, female very old; 51 cases and 55 lesions. Multiple gastric
      cancers were more frequent in female older group. In early cancer the frequency
      of elevated type increased significantly and that of depressed type decreased in
      very old group. In advanced cancer Borrmann I type was not so common in very old
      group. Histologically the frequency of signet ring cell cancer decreased and of
      tubular adenocarcinoma and of papillary adenocarcinoma increased significantly in
      female very old group. Hepatic metastasis increased significantly in male very
      old group. Lymph node metastasis and peritoneal metastasis did not show any
      change in age-related frequency.

PMID- 7563938
TI  - [Perceived quality of life and social factors in elderly hypertensive patients].
AB  - We conducted a cross-sectional study of elderly outpatients with hypertension to
      examine the relationship between quality of life (QOL) scores and social
      background factors. The subjects consisted of 516 outpatients (267 females), age
      of 60 or over, at nine clinics of major hospitals which participated in the
      National Cardiovascular Center Research Project. The perceived QOL was evaluated
      by the QOL scale originally based on Japanese patients with cardiovascular
      diseases. The scale consisted of the following 5 subscales; difficulty due to
      disease, psychological stability, independence, satisfaction in daily living and
      vitality. The background factors included family structure, socioeconomic factors
      and work status, and physical activity of daily living (ADL). After adjusting for
      age, sex, administered drugs and complicating conditions such as ischemic heart
      disease and/or apoplexy, a significant odds ratio of a low score of difficulty
      due to disease, psychological stability, satisfaction in daily living and
      vitality was found in the impaired physical ADL group with low socioeconomic
      class, and a significant odds ratio of low score of independence were found in
      the impaired physical ADL group who had lost jobs due to illness and had no
      children.

PMID- 7563939
TI  - [Successful treatment of a 74-year-old man with refractory anemia with excess of
      blasts in transformation (RAEB in T) by low-dose Ara-C injection].
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic
      disorders characterized by normal or hypercellular but dysfunctional bone marrow.
      They usually are refractory to empirical therapeutic regimens. Recently the
      prevalence of MDS in the elderly is increasing and now the syndromes are
      relatively commonly encountered in elderly patients. Two major causes of death in
      MDS are progression to acute leukemia (especially in subtypes of RAEB and RAEB in
      T), and bone marrow aplasia. Since cytoreductive therapy for RAEB or RAEB in T in
      the elderly is often accompanied by serious adverse complications, such as
      infection and hemorrhage, special care is necessary. Here we describe successful
      induction remission in a 74-year-old man with MDS (RAEB in T) by twice daily low
      dose cytosine arabinoside injections (10 mg/m2, s.c.), which was well-tolerated,
      free of serious adverse effects, and seemed to be a useful therapeutic option for
      elderly patient with RAEB or RAEB in T.

PMID- 7563940
TI  - [A case of multiple sclerosis associated with lateralization of bone change].
AB  - We report a 63-year-old female, case of multiple sclerosis associated with
      lateralization of bone change. In 1969, at age 38 she lost sight in her right
      eye. After that, she had several episodes of remission and exacerbation. In 1992,
      left hemiparesis, sensory disturbance and vesicorectal disturbance appeared, and
      she was admitted to our hospital. Immediately, steroid pulse-therapy was
      initiated then steroids were tapered. Her muscle strength recovered to some
      degree. The left upper limb showed low skin temperature, edema and decreased
      circulation. In January and September of 1993, bone examinations were conducted
      using multiple scanning X-ray photodensitometry. Osteopenia was observed,
      especially in the left hand. The bone density in the right hand changed slightly
      during the 8-month course of the illness, but osteopenia in the left hand became
      more marked. The asymmetrical bone change suggested that osteopenia results from
      a disorder of the central nervous system, especially through autonomic disorder.

PMID- 7563941
TI  - Estimation of age from image processing of soft X-ray findings in Japanese male
      thyroid cartilages.
AB  - A method was developed for estimating the age at death based on image processing
      of soft X-ray pictures of thyroid cartilage from Japanese males. Data for 501
      individuals were used to derive equations for this determination. Prior to image
      processing, gross morphological findings were used for estimation. Soft X-ray
      pictures indicated ossification with age and one index for image processing was
      introduced. The exponential function was applied to age estimation.

PMID- 7563942
TI  - Estimation of age from soft X-ray findings of Japanese females thyroid
      cartilages.
AB  - A method for estimating the age at death using the image processing of soft X-ray
      pictures of the thyroid cartilages of Japanese females was examined. The soft X
      ray pictures showed increasing ossification with age. One index for image
      processing was introduced. It is ossification rate (OSFR). Corresponding to this
      index, one age estimation equation was obtained. This age estimation equation
      showed accuracies of 60% or more for the age range of +/- 5 years and about 80%
      for the age range of +/- 8 years.

PMID- 7563943
TI  - [Sequence polymorphism of mitochondrial DNA and its forensic application].
AB  - We have investigated polymorphism of mitochondrial (mt) DNAs in the Japanese
      population. In order to compare 288-bp sequences (nucleotide positions 16,111 to
      16,398) in the noncoding region, a 452-bp segment elongated by 82 bp at both
      sides of the target was amplified by PCR and analyzed directly by Taq cycle
      sequencing with FITC-labelled primers. A survey of 100 Japanese individuals
      revealed the existence of 66 types of mtDNAs. Among them, 10 types including two
      frequent types were shared by more than one individual. During this
      investigation, it was found that 19 types (from 25 individuals) possessed a
      common nucleotide replacement of T by C at position 16,189, by which a "C
      continuous stretch" was formed, and that clear reading of their sequences was
      restricted in the region lying ahead of the C stretch on either forward or
      reverse sequencing. Cloning analysis of PCR product possessing the C stretch
      demonstrated that the length of the C stretch was heterogeneous. Consequently, we
      propose the following rules for mtDNA sequencing and its forensic application: 1)
      the replacement of T by C at position 16,189 is acceptable as a variation factor.
      2) The number of Cs in the C stretch is tentatively fixed at 10.

PMID- 7563944
TI  - Preparation of multi-locus DNA probe cocktail by liquid-phase reassociation.
AB  - We developed a simple, rapid method for the preparation of a DNA-fingerprinting
      probe cocktail, and tested its usefulness in paternity testing. Exploiting the
      property of tandemly repetitive DNA segments to be rapidly renatured after heat
      denaturation, we enriched restriction fragments of a child's genomic DNA for
      minisatellites by liquid phase reassociation followed by capture with immobilized
      streptavidin. We amplified and simultaneously labeled the reassociation product
      by anchored PCR using a digoxigenin-labeling mixture. Using this probe cocktail,
      we were able to detect fingerprints of paternity case trios, and the results were
      corroborated by DNA fingerprinting with a commercially available probe as well as
      by conventional phenotyping. Our method enables one to prepare a fresh cocktail
      of probes from the DNA sample under study during the overnight electrophoresis
      and Southern transfer steps in DNA fingerprinting, and eliminates the need of
      having an expensive probe of limited shelf life. If one has a practical outlook
      on DNA fingerprinting and regard it as a preliminary test, one does not have to
      use a cloned DNA probe. The present study demonstrates that a multi-locus probe
      cocktail serves such a practical purpose.

PMID- 7563945
TI  - Death due to asphyxia linked to antipsychotic drugs.
AB  - A 46-year-old man with schizophrenia, died in hospital. Autopsy revealed numerous
      facial injuries and the direct cause of death was apparently asphyxia as a large
      amount of coagulated blood was present in the lower part of the trachea and
      bronchi. The blood derived from a lacerated wound of the mouth. The question was
      raised as to why expectoration was impossible and a toxicological analysis was
      directed to the antipsychotic drugs allegedly prescribed by doctors at the
      hospital. Using gas chromatography and gas chromatography/mass spectrometry, four
      different antipsychotic drugs including chlorpromazine, levomepromazine, zotepine
      and haloperidol were identified in the whole blood and tissues with
      concentrations being 1.91, 0.75, 0.61 and 0.48 micrograms/g in the blood,
      respectively. These levels were toxic to the extent that he could not expectorate
      and blood accumulating in the airway led to asphyxia and death.

PMID- 7563946
TI  - Autopsy cases of giant heart during the past ten years in Osaka (1985-1994).
AB  - We collected data from 30 autopsied cases, in which the heart weight were 800 g
      or more (maximum 1,300 g), at the Osaka Medical Examiner's office, for past 10
      years. Among these cases, the cause of death was cardiac failure in 17 cases
      (56.7%), followed by pulmonary diseases (3 cases, 10.0%), cerebral infarction (3
      cases, 10.0%), and aortic rupture (2 cases, 6.6%). The mean weight of the giant
      hearts was 880 g (about 77% of the cases) and 4 cases (13%) had 1,000 g or more.
      The mean height of the giant heart victims was close to the standard level, and
      thus the mean level of the ratio of heart weight to height were about 2.5 times
      higher than the standard levels. The liver weights were also greater by 500-1,000
      g than the standard levels.

PMID- 7563947
TI  - [Deaths due to heat waves during the summer of 1994 in Osaka Prefecture, Japan].
AB  - The summer of 1994 was unusually hot and dry in Japan, setting a record for high
      temperature and low rainfall in many areas. The daily record of temperature of
      July and August which were announced by Osaka District Meteorological Observatory
      exceeded the past ones. The daily recorded temperature of 75 consecutive days in
      Osaka city was above 30 degrees C with the maximum 39.1 degrees C on 18 August
      1994 and 38 degrees C on 16 July 1994. The number of unusual deaths (except
      traffic accidents) in Osaka Prefecture was 655 and 733 in the month of July and
      August respectively which exceeded the number of death for the corresponding
      period of the last 5 consecutive years by 1.5 folds, which was directly
      proportionate to the change of temperatures. This was due to the illness of the
      people concerned. We investigated the age, sex and rectal temperature during the
      inquest and compared them with those of the same period of 1992, which we kept as
      control. On comparing age and sex of the dead bodies, the cases of 1994 were
      older than those of 1992, which was due to increased number of death of female
      aged 70 or more. On comparing the rectal temperatures of those who were found
      indoors within 8 hours after death, the average temperature of 1994 was also
      higher than that of 1992. Between the age groups of 75 or more and 74 or younger,
      the rectal temperature of the former is significantly higher than those of later
      age group. While regarding the room temperature of the high rectal temperature
      (39 degrees C < or =) group, no significant difference was observed between the
      age groups of 75 or more and 74 or younger. In general, the number of unusual
      deaths in the summer of 1994 in Osaka was more compared to those of previous
      years. The analysis of the recorded rectal temperatures demonstrated that, 75 or
      older age group has a tendency to hyperthermia. Since the aging society of Japan
      is gradually increasing, preventive measures will be necessary when forecasting
      heat wave to reduce the morbidity and mortality of the aged people.

PMID- 7563948
TI  - Clinical guidelines of IgA nephropathy.

PMID- 7563949
TI  - Cloning of a pH sensitive K+ channel in the kidney.
AB  - The renal collecting tubules are responsible for secretion of K+ into the urine
      and play a major regulatory role in K+ homeostasis of mammals. There are several
      factors which affect K+ secretion, including aldosterone, K intakes and acid-base
      balance. We have cloned a complementary DNA encoding a K+ channel of the rabbit
      renal cortical collecting tubule cells (RACTK1). RACTK1 is a voltage-independent,
      pH sensitive K(+)-permeable channel, encoding 284 amino-acids, and putatively
      having two transmembrane segments. This channel is located not only in the
      luminal membrane of the collecting duct but also in the vascular smooth muscles
      of the several arteries. The expression of RACTK1 is regulated by external pH but
      neither by aldosterone nor by K+ concentration in cultured cells. Thus RACTK1
      seems to be a unique and distinct from K+ channels in that it is regulated
      specifically by changes in ambient pH, contributing to the pH dependent urinary
      K+ excretion.

PMID- 7563950
TI  - Difference of myosin heavy chain expression between mesangial cells and vascular
      smooth muscles.
AB  - Contraction of the pre- and postglomerular arteries play an important role in the
      regulation of glomerular blood flow. Mesangial cells may also be involved in the
      mechanism of this regulation, but it has not been clarified yet whether or not
      mesangial cells and vascular smooth muscles show an identical phenotype,
      especially in terms of their contractile proteins. In this study, in order to
      elucidate any difference in the cellular phenotypes between mesangial cells and
      renal vascular smooth muscles, we investigated the localization of myosin heavy
      chain isoforms using a monoclonal antibody against SM1 and SM2. Both SM1 and SM2
      are specific to smooth muscles. SM1 is specifically expressed in smooth muscles
      from early development and SM2 appears after birth. In normal renal tissues, SM1
      and SM2 were expressed only in the smooth muscle cells of the arterioles and
      small arteries. However, glomerular cells, including mesangial cells, were not
      stained with either anti-SM1 antibody or anti-SM2 antibody. Localization of SM1
      and SM-2 was similar to that of alpha-smooth muscle actin (SM alpha-actin).
      Staining for SM-1 was not observed in the mesangial areas of renal tissues with
      glomerular disease. These results clearly indicate that mesangial cells have a
      different phenotype from that of vascular smooth muscle cells in terms of their
      contractile proteins.

PMID- 7563951
TI  - Loop diuretics act directly on adenylate cyclase in rat renal tubular basolateral
      membranes.
AB  - We have reported previously that loop diuretics, especially azosemide and
      ethacrynic acid, may act not only on the AVP receptor site, but also on the post
      AVP receptor site in rat renal tubular basolateral membranes. The purpose of this
      study was to examine whether loop diuretics (furosemide, azosemide, ethacrynic
      acid) affect the post-AVP receptor components, using GTP-gamma S, forskolin and
      cholera toxin as tools acting distal to the receptor. Adenylate cyclase activity
      stimulated by 10(-9)M AVP was inhibited more potently by azosemide and ethacrynic
      acid than by furosemide at the concentration of 10(-3) M. Azosemide and
      ethacrynic acid at concentrations above 10(-4) M also significantly decreased the
      enzyme activity that was stimulated by 10(-7) M GTP-gamma S and 10(-5)M
      forskolin, while significant inhibition by furosemide was observed only at 10(
      3)M. In addition, the inhibitory effect of these loop diuretics on cholera toxin
      stimulated enzyme activity was almost similar to the results observed in AVP-,
      GTP-gamma S- or forskolin-stimulated the enzyme activity. From these results, we
      conclude that loop diuretics, especially azosemide and ethacrynic acid, directly
      affect adenylate cyclase in part as well as the AVP receptor site.

PMID- 7563952
TI  - A clinicopathological study of idiopathic nephrotic syndrome in children.
AB  - This paper retrospectively examines the association of outcome with histological
      and clinical manifestations in 107 pediatric patients with idiopathic nephrotic
      syndrome (INS). At the time of renal biopsy, the patients were between 2 and 15
      years of age. The interval from the onset of the disease to renal biopsy ranged
      from 1 to 156 months with a mean of 21 months. Continuous clinical follow-up was
      successfully conducted in 96 patients. The average duration of INS in these
      patients was 86.6 months (31 to 208 months). IgM deposition in the mesangium may
      play an important role in the pathogenesis of INS and our data showed that even
      in a minor glomerular abnormality (MCNS) subgroup, nearly half of the cases
      (42.9%) showed mesangial IgM deposition. However, the severity of hematuria,
      response to drug therapy with either steroids or cyclophosphamide, and the
      outcome, were not related to the presence or absence of IgM deposition, but were
      more closely associated with the type of histological category. The subgroup of
      patients with focal segmental glomerulosclerosis (FSGS) and diffuse mesangial
      proliferation (FSGS + DP) showed the most significant ultrastructural changes
      with positive mesangial IgM deposition (73.6%). The presence of IgM deposition in
      most of the patients in the subgroups with diffuse mesangial proliferative
      glomerulonephritis (DPGN) and FSGS + DP closely corresponded to the presence of
      electron-dense mesangial deposition. The FSGS + DP subgroup had a high incidence
      of denudation, vacuolization and detachment of podocytes, partial collapse of the
      glomerular basement membrane, and a very high incidence of resistance to steroid
      therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7563953
TI  - Histomorphometric study in children with idiopathic nephrotic syndrome.
AB  - From 1981 to 1987, renal specimens obtained from 91 children with idiopathic
      nephrotic syndrome were categorized into 5 histologic subgroups, according to the
      WHO classification. We analyzed differences in the ratios of the size of the
      mesangial stalks and attached capillary, including the Bowman's space between the
      capillary tufts (E), mesangial matrix (Mx), and approximate capillary lumens (E
      Mx) to the whole glomerular area of these subgroups using the histomorphometer
      IBAS. Focal segmental glomerulosclerosis with diffuse mesangial proliferation
      (FSGS + DP) had the largest matrix area (Mx/G > 0.5), and smallest capillary
      lumen size (E/G-Mx/G) (0.3474 +/- 0.0702). On the contrary, FSGS with minimal
      change (FSGS + MC) had the smallest mesangial matrix (Mx/G), 0.2834 +/- 0.07726,
      but preserved a larger capillary lumen (0.427 +/- 0.1215). The approximate size
      of capillary lumens, from the smallest to the largest, was in the following
      order: FSGS + DP, diffuse mesangial proliferative glomerulonephritis (DPGN),
      focal segmental proliferative glomerulonephritis (FSPGN), FSGS + MC and minimal
      change nephrotic syndrome (MCNS). The ratio of the total number of mesangial
      cells to the area of the whole glomerulus (MCN/G) derived from the light
      microscopic examination was parallel to the value of Mx/G obtained by the
      histomorphometric technique. In summary, we introduced the histomorphometric
      technique using the histomorphometer-IBAS for quantitative measurement of various
      areas in the glomeruli. The data derived from the system is compatible with those
      obtained by experienced nephrologists, suggesting that the histomorphometric
      technique is helpful in histopathology. It is hoped that this new methodology
      will be used more extensively in the near future.

PMID- 7563954
TI  - Clinicopathological study of dialysis patients with lupus nephritis.
AB  - To determine the clinical characteristics and long-term prognosis of 11 Japanese
      systemic lupus erythematosus (SLE) patients who were starting dialysis, we
      studied the clinicopathological findings before dialysis and during the clinical
      course after dialysis. Patients were divided into three groups: Group A
      consisting of temporary dialysis patients (n = 5); Group B consisting of early
      death patient (n = 1); and Group C consisting of maintenance dialysis patients (n
      = 6). At the start of dialysis, the progression pattern of renal failure in all
      Group A patients was either acute exacerbation of chronic renal failure (CRF) or
      rapidly progressive glomerulonephritis (RPGN). The pattern in Group C was mostly
      CRF (83%). Three patients from Group A and three from Group C were still alive at
      the latest follow-up (mean follow-up period was 11.0 years, ranging from 1.8 to
      16.2 years) and they showed no signs of clinical or serological activity.
      Infection was the cause of death in 3 of the 5 patients who died. We suggest that
      dialysis can be discontinued in patients with SLE who receive dialysis for acute
      exacerbation of CRF or RPGN. After the initiation of dialysis, patients tend to
      show diminished SLE activity. Infection is the major contributor to the poor
      prognosis of SLE patients receiving dialysis.

PMID- 7563955
TI  - Participation of histones and ubiquitin in lupus nephritis.
AB  - To evaluate the role of histones and ubiquitin in lupus nephritis, we searched
      for glomerular deposits of histones and ubiquitin in renal biopsy specimens from
      53 patients with systemic lupus erythematosus (SLE) and 30 with non-lupus
      glomerulonephritis. Glomerular immunofluorescence staining revealed positive for
      histone H2A, H1 + H3, H4 and ubiquitin in 49.1% (26/53), 45.3% (24/53), 32.1%
      (17/53) and 22.6% (12/53) of the SLE patients, respectively. Non-SLE renal
      biopsies revealed absence of positive staining with histone H2A, H1 + H3, H4 and
      ubiquitin. The positive incidence of histone H1 + H3 and ubiquitin in diffuse
      proliferative lupus nephritis was significantly different (p < 0.01) from that in
      minor glomerular abnormality. Levels of CH50 in patients with glomerular
      deposition of histone H1 + H3 (p < 0.001) and ubiquitin (p < 0.01) were
      significantly lower than in patients without deposition. Levels of anti-DNA
      antibody in patients with glomerular deposition of histone H1 + H3 were
      significantly higher than in patients without deposition (p < 0.05). Only the
      positive incidence of glomerular deposition of ubiquitin was correlated with the
      histological activity index (p < 0.05). These results suggest that histones and
      ubiquitin may play an important role in the induction of lupus nephritis.

PMID- 7563956
TI  - Effect of iron as a new type of phosphate binder in hemodialysis patients.
AB  - Hyperphosphatemia is one of the major problems requiring management in the
      majority of hemodialysis patients and they require phosphate-binding agents to
      control the hyperphosphatemia. Aluminum hydroxide and calcium compounds are used
      currently as phosphate-binding agents to treat hyperphosphatemia, but these
      compounds can cause undesirable side effects. Therefore, the development of new
      phosphate-binding agents is imperative. It is well known that oral and
      intravenous administration of iron causes hypophosphatemia. We hypothesized that
      this side effect of iron may be beneficial for the treatment of hyperphosphatemia
      in hemodialysis patients. Consequently, we conducted a fundamental and clinical
      investigation of the effects of iron administration. Membrane permeability of
      phosphorus in a mixture of sodium ferrous citrate and dessicated aluminium
      hydroxide in the presence of hydrogenated lecithin as a phosporic compound was
      examined. Fifteen patients undergoing hemodialysis were treated with 150 mg of
      sodium ferrous citrate given orally for eight weeks. The permeability of the
      filtering membrane to phosphorus decreased in accordance with the dosage of
      sodium ferrous citrate and dessicated aluminum hydroxide. The degree of phosphate
      binding effect of sodium ferrous citrate was larger than that of dessicated
      aluminum hydroxide. Serum phosphorus decreased significantly during the
      experiment. These results suggest that the oral administration of sodium ferrous
      citrate as a new phosphate binder is a useful therapeutic method for hemodialysis
      in patients with hyperphosphatemia.

PMID- 7563958
TI  - [The 35th annual meeting of the Japanese Society of Nuclear Medicine. October 4
      6, Yokohama, Japan].

PMID- 7563957
TI  - Late-onset renal dysfunction in a patient with non-Hodgkin's lymphoma following
      an autologous bone marrow transplantation.
AB  - Various types of glomerulonephropathy have been reported in patients with
      malignant lymphoma. The present report describes a 21-year-old man with non
      Hodgkin's lymphoma who developed renal insufficiency 4 months after undergoing
      autologous bone marrow transplantation without combined total body irradiation
      treatment. At the presentation of renal dysfunction, the malignant lymphoma had
      been in complete remission. A renal biopsy specimen revealed glomerular changes
      resembling those seen in patients with hemolytic uremic syndrome. However,
      hematologic examinations exhibited no evidence of thrombocytopenia or thrombotic
      microangiopathy, such as red cell fragmentations on the peripheral blood smear.
      Although the etiology of this nephropathy remains unclear, the chemotherapeutic
      agents administered in conditioning regimens for bone marrow transplantation were
      suspected of contributing to the renal insufficiency. Methylprednisolone pulse
      therapy appeared to be effective in arresting progression of the nephropathy.
      This case indicates that renal function should be monitored carefully in patients
      with malignant lymphoma after bone marrow transplantation, even if such patients
      lack the signs or symptoms of thrombotic microangiopathy.

PMID- 7563959
TI  - Differential control of proceptive and receptive components of female rat sexual
      behavior by the preoptic area.

PMID- 7563960
TI  - Restricted diffusion of an 19F-labelled organic acid in human erythrocytes
      analyzed by 19F pulsed field gradient NMR.
AB  - The diffusion coefficient of an 19F-labelled organic acid (3
      trifluoromethylhippurate: TFMH) was measured in intact human red blood cells
      (RBCs) and sealed right-side-out ghosts at 22.5 +/- 0.05 degrees C. Diffusion
      coefficients were measured using stimulated echo and spin-echo pulsed field
      gradient sequences. The apparent diffusion coefficient (Da) of TFMH in the
      intracellular space was much smaller than in the extracellular medium. This was
      due to restricted diffusion of intracellular TFMH since i) the intracellular Da
      decreased when the diffusion time was increased, and ii) the smaller Da component
      disappeared when the membrane was permeabilized with saponin. From the
      intracellular Da values obtained over a range of diffusion times, from 5 ms to 1
      s, the apparent radius of the diffusion barrier was estimated to be 3 +/- 1.1
      micron assuming spherical geometry. Despite the high protein concentration in the
      intracellular space of the intact RBC, the intracellular values of Da were
      similar to the values obtained in the ghosts at the same diffusion times. We
      therefore conclude that the small diffusion coefficient of intracellular TFMH is
      mainly explained by the restricted diffusion due to the cell boundary.

PMID- 7563961
TI  - Potentiation of cholecystokinin-induced amylase release by peptide VIP in guinea
      pig pancreatic acini.
AB  - The mechanism of the potentiating effect of vasoactive intestinal peptide (VIP)
      on cholecystokinin (CCK-8)-induced amylase release was studied in isolated and
      perifused pancreatic acini of the guinea pig. VIP (30 pM-10 nM) potentiated CCK-8
      (100 pM)-induced amylase release. Unexpectedly, VIP inhibited CCK-8-induced
      intracellular Ca2+ oscillations. Forskolin (10 microM), an activator of adenylate
      cyclase, potentiated CCK-8 (100 pM)-induced amylase release with a time course
      similar to that observed with VIP. Caffeine (20 mM) inhibited both amylase
      release and Ca2+ oscillations in response to CCK-8, suggesting that inhibition of
      Ca2+ oscillations does not necessarily lead to a potentiation of amylase release.
      When intracellular Ca2+ concentration ([Ca2+]c) was raised by thapsigargin (10
      microM), a selective inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum
      (ER), VIP (10 nM) induced significantly greater amylase release than that induced
      by VIP alone. When [Ca2+]c was lowered by preincubation with BAPTA-AM (25
      microM), a cell-permeant Ca2+ chelator, VIP-induced amylase release was
      completely abolished. These results suggest that VIP, in spite of its inhibitory
      action on Ca2+ oscillations, facilitates a Ca(2+)-dependent process distal to the
      increase in [Ca2+]c to potentiate CCK-8-induced amylase release.

PMID- 7563962
TI  - Effects of chronic iron deficiency anemia on brain metabolism.
AB  - The effects of chronic iron deficiency anemia on brain (cortex) metabolism were
      estimated by 31P-nuclear magnetic resonance spectroscopy and biochemical analyses
      in male Wistar rats. Iron deficiency anemia was induced by supplying diet
      containing either approximately 2 or approximately 6 ppm Fe. Control diet was
      supplemented with 100 ppm Fe as ferric citrate. After 8-9 weeks, blood hemoglobin
      levels were approximately 13, 5, and 3 g/100 ml in the 100 ppm, 6 ppm, and 2 ppm
      Fe group, respectively. The blood lactate levels at rest in these groups were
      approximately 3, 5, and 6 mM. The blood glucose concentration also tended to be
      elevated in iron-deficient rats. The high-energy phosphate contents in brain were
      not affected by iron deficiency. The activities of succinate dehydrogenase and
      cytochrome oxidase per unit protein in the 2 ppm Fe group were significantly less
      than in the 100 ppm Fe group, but those activities were not significantly
      affected by feeding diet with 6 ppm Fe. The activities of lactate dehydrogenase
      in iron-deficient group tended to be elevated but not significantly. The
      activities of non-iron containing mitochondrial enzymes, citrate synthase and
      beta-hydroxyacyl CoA dehydrogenase, were unchanged. It is suggested that the
      brain has a higher tolerance to iron deficiency than skeletal muscle in terms of
      the metabolic characteristics, although this may be associated with a lower level
      of neural activity.

PMID- 7563963
TI  - Sympathetic efferent activity in the viscerovascular reflexes induced by urinary
      bladder distension.
AB  - In chloralose-anesthetized cats, rapid distension of the urinary bladder with
      warm (37 degrees C) normal saline (50-60 ml) causes an increase in blood pressure
      and contraction of the spleen. This response is due to peripheral
      vasoconstriction. In this experiment, the evidence of direct involvement of the
      spleen, as well as splenic and splanchnic sympathetic efferent activity on the
      viscerovascular reflexes, was investigated by pharmacological and
      electrophysiological (single unit preparation) means and analysis. The
      viscerovascular reflexes induced by urinary bladder distension remained
      unaffected by propranolol, but phentolamine, guanethidine sulfate, and
      hexamethonium completely antagonized the reflex vasopressor response. All these
      results with these blocking agents show that sympathetic nerves are actively
      involved in the reflex responses to distension of the urinary bladder with
      activation at the postganglionic level involving alpha-adrenoceptors and thereby
      the release of catecholamines. It is thus evident that the same mechanisms
      operate in the case of reflex elevation of blood pressure and contraction of the
      spleen. After bilateral denervation of the splanchnic sympathetic nerves, bladder
      distension failed to produce a reflex response. The efferent activity from the
      splanchnic and splenic sympathetic nerves in producing a reflex rise in blood
      pressure was recorded for direct evidence. The significant increase of
      asynchronous spontaneous discharge rate in the splanchnic and splenic sympathetic
      nerves was found along with a rise in blood pressure during bladder distension.
      On the basis of this study, it may be suggested that the spleen as well as
      splenic and splanchnic sympathetic nerves play an important role in the control
      of viscerovascular reflexes.

PMID- 7563964
TI  - Different effects of removing extracellular Ca2+ on cytosolic Ca2+ response to
      anoxia of sensory neurons and carotid chemoreceptor cells from newborn rabbits.
AB  - To study the mechanism of the increases in cytosolic Ca2+ ([Ca2+]i) induced by
      anoxia, the author examined the effect of removing extracellular Ca2+ on the
      [Ca2+]i response in cultured nodose ganglion neurons (control) and carotid body
      glomus cells prepared from newborn rabbits using a fura-2 microfluorimetry. The
      sensory neurons showed a small increase in [Ca2+]i during anoxia which was not
      affected by the removal of extracellular Ca2+ or D600. On the other hand, in the
      chemoreceptor glomus cells, Ca2+ removal eliminated the anoxia-induced large
      [Ca2+]i increase in 85% of the tested cells (n = 67), and depressed it in the
      rest. Interestingly, recovery from exposure to an anoxic Ca(2+)-free solution
      reversibly produced a large and transient rise in [Ca2+]i. The magnitude of this
      post-anoxic/Ca(2+)-free [Ca2+]i transient correlated with the intensity of the
      suppression of the [Ca2+]i response to anoxia in Ca(2+)-free solution. Also the
      [Ca2+]i transient was mostly inhibited by L-type Ca2+ channel blockers
      (nifedipine and D600), but was not affected by tetrodotoxin. These results
      suggest that the anoxia-induced large increase in [Ca2+]i were, in most glomus
      cells, coming from extracellular sources and, in a few cells, from both
      extracellular sources and from intracellular pools, whereas the slight increase
      in [Ca2+]i in sensory neurons was probably produced by releasing Ca2+ from
      intracellular stores. The post-anoxic/Ca(2+)-free [Ca2+]i transient, seen in the
      chemoreceptor cells alone, may have resulted from modification of the anoxic
      [Ca2+]i response by Ca2+ removal and involves mostly L-type Ca2+ channels and a
      few other Ca2+ entry pathways.

PMID- 7563966
TI  - Dynamical features of thermoregulatory model of sleep control.
AB  - We have developed a quantitative model of human sleep-wake rhythms based on a
      thermoregulatory feedback control mechanism modulated by two circadian
      oscillators. Homeostatic features of sleep regulation are realized through the
      heat memory which represents the history of the masking process associated with
      sleep-wake cycles: heat load during wake and heat loss during sleep. Simulations
      under entrained conditions showed that the model closely mimics well-known
      features of human sleep-wake rhythm, and that the homeostatic and the oscillatory
      aspects of the human circadian system are successfully integrated in our model.
      In this paper, parameter dependency of the model behavior is studied by
      simulations. Because of its physiology-based structure, the parameter dependency
      could show the possible underlying mechanism for the typical features of human
      sleep-wake rhythm. In addition, the model stability is analyzed by the linear
      system theory and the simulations, which establishes the stability condition and
      suggests that the presented simulation results are basically stable. These
      results are informative to apply our model to actual data of sleep-wake rhythms,
      and to interpret them from the physiological point of view.

PMID- 7563965
TI  - A thermoregulatory model of sleep control.
AB  - We hypothesize that non-rapid-eye-movement sleep (NREM) is controlled by
      thermoregulatory mechanisms of the preoptic/anterior hypothalamus. Circadian and
      homeostatic thermoregulatory processes may be integrated in this brain area. To
      investigate this hypothesis, we have developed a mathematical model of
      qualitative features of human sleep-waking behavior based on a thermoregulatory
      feedback control mechanism, with modulation by two circadian oscillators, one a
      temperature rhythm, the other modulating sleepiness. Homeostatic features of the
      sleep rhythm are generated by integration of a heat load associated with waking.
      Simulations under entrained conditions show that the model closely mimics typical
      features of human sleep rhythms, including a biphasic daily pattern of sleepiness
      and sleep-onsets and awakenings fixed in a descending phase and an ascending
      phase of the temperature rhythm, respectively. Sleep duration is strongly
      controlled by the phase difference between the two oscillators with the same
      period; these could represent two phase-differentiated expressions of a single
      oscillator. In addition, the simulation of sleep deprivation provides a natural
      interpretation of the experimentally observed phenomena, which shows that the
      homeostatic and the oscillatory aspects of the human circadian system is
      successfully integrated in our model. The promising results obtained suggest that
      the control of sleep-wake rhythm could be understood within the framework of the
      thermoregulation.

PMID- 7563967
TI  - The effect of intravenous infusion of L-arginine, glycine and D-lysine on urinary
      calcium excretion in the rat.
AB  - Standard renal clearance techniques were used to compare the effects of
      intravenous infusions of L-arginine, D-lysine and glycine on urinary calcium
      excretion in the rat. A significant calciuric response was evident following the
      infusion of all three amino acids in all the animals. The maximal effect was
      evident in rats receiving L-arginine. The mechanism for the increased urinary
      calcium excretion in rats infused with L-arginine and D-lysine appeared more due
      to a decreased fractional reabsorption of this cation as no significant changes
      in the glomerular filtration rate (GFR) were evident in these two groups. The
      calciuria in rats receiving glycine appears due to increased filtered load
      secondary to the increased GFR, suggesting that the mechanism for calciuria
      evident following protein ingestion or amino acid infusion may vary and may be
      dependent upon the amino acid ingested or infused.

PMID- 7563968
TI  - Transient increase in human muscle sympathetic nerve activity during manual
      acupuncture.
AB  - To clarify the effects of manual acupuncture on the autonomic nervous system, we
      measured efferent muscle sympathetic nerve activity (MSNA) from the right
      peroneal nerve while simultaneously recording blood pressure and heart rate both
      during the resting period and after manual acupuncture applied to the Tsusanli
      acupoint of the same limb. The needle was rotated intermittently for 30 s at 5
      min intervals. MSNA increased transiently with the suppression of heart rate
      during rotation of the acupuncture needle. No consistent change in blood pressure
      was found throughout the acupuncture session. After removal of the needle, both
      the MSNA and heart rate returned to the initial control values, and the mean
      blood pressure showed an increase over the resting value. MSNA showed a negative
      correlation with heart rate in four out of five subjects who received
      acupuncture. These results suggest that the coactivation of cardiac vagal and
      muscle sympathetic nerves is evoked by the acupuncture maneuver.

PMID- 7563969
TI  - Increased and decreased choroidal blood flow elicited by cervical sympathetic
      nerve stimulation in the cat.
AB  - The effect of electrical stimulation of the cervical sympathetic nerve on
      choroidal blood flow in the cat was investigated. Flow at various sites in 30
      pentobarbital-anesthetized cats was continuously measured trans-sclerally using a
      laser Doppler flowmeter. Changes in either direction, increases and decreases,
      occurred in response to electrical stimulation of the peripheral cut end of the
      cervical sympathetic nerve. These changes in flow appeared to depend on the site
      of choroidal blood flow measurement, as decreases were seen at sites with a high
      baseline blood flow and increases at sites with a low baseline level. Both types
      of response were reduced when the cats were treated with the alpha-adrenoreceptor
      antagonist phentolamine, but not by treatment with the beta-adrenoceptor
      antagonist propranolol. The decrease in choroidal blood flow elicited by cervical
      sympathetic nerve stimulation appears to be mediated via the vasoconstrictor
      fibers in that nerve. A choroidal blood flow increase may occur as a secondary
      effect following vasoconstriction of the arterioles elicited by cervical
      sympathetic nerve stimulation, producing a passive net increase in choroidal
      blood flow.

PMID- 7563970
TI  - Effect of DP-1904, a thromboxane A2 synthase inhibitor, administered from the
      autologous phase on crescentic-type anti-GBM nephritis in rats.
AB  - The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8
      tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane (TX) A2
      synthase inhibitor, was compared with that of OKY-046 and azathioprine, using an
      experimental model of nephritis, crescentic-type anti-glomerular basement
      membrane (GBM) nephritis. Test drugs were given p.o. once daily from an
      autologous phase in which proteinuria was already fully developed. DP-1904 (15
      and 45 mg/kg per day) and OKY-046 (20 mg/kg per day), another TXA2 synthase
      inhibitor, significantly inhibited the development of glomerular alteration as
      well as the elevation of proteinuria. On the other hand, azathioprine (20 mg/kg
      per day), an immunosuppressive agent, failed to suppress the proteinuria. A
      single administration of DP-1904 or OKY-046 inhibited glomerular TXB2 production
      and increased glomerular prostaglandin (PG) E2 and 6-keto PGF1 alpha production
      in nephritic rats. Both drugs apparently decreased the depositions of both rabbit
      immunoglobulin (Ig) G and rat IgG on GBM in nephritic rats, but azathioprine
      inhibited only the deposition of rat IgG. These results suggest that DP-1904 may
      be an effective agent for the treatment of proliferative glomerulonephritis and
      its antinephritic effect may be due to the amelioration of abnormal metabolism of
      arachidonic acid.

PMID- 7563972
TI  - Effects of strontium on calcium metabolism in rats. II. Strontium prevents the
      increased rate of bone turnover in ovariectomized rats.
AB  - The effects of stable strontium were investigated in ovariectomized (OVX) rats by
      calcium balance and calcium kinetic studies, histomorphometric analysis and
      measurements of calcium levels in bone. After 10 days of pair-feeding with a
      control diet, 71-day-old female Wistar rats were either sham-operated (Sham
      group) or ovariectomized. The OVX rats were divided into two subgroups: those
      that were treated with strontium (OVX+Sr group, strontium intake; 87.5
      mumol/day/rat) and those that were not (OVX group). Both groups were pair-fed
      their respective control or strontium diets for 2 weeks. Calcein and tetracycline
      were injected every 2 weeks from 1 week before ovariectomy to calculate the rate
      of bone formation in the diaphyseal femora cortex (% BFFC). In the OVX group,
      urinary calcium and % BFFC decreased, while bone resorption, bone formation and
      femora length increased at the end of the experiment, as compared with those in
      the Sham group. No such changes were observed in rats in the OVX+Sr group. The
      calcium balance, calcium levels in bone and trabecular bone volume in the
      metaphysis did not change in any of the three groups. These results suggest that
      strontium may be able to prevent the changes in bone turnover induced by estrogen
      deficiency.

PMID- 7563971
TI  - Comparative study of vasodilator effects of the potassium channel openers NIP-121
      and levcromakalim in dogs and rats.
AB  - The effects of potassium channel openers NIP-121 ((+)-7,8-dihydro-6,6-dimethyl-7
      hydroxy-8-(2-oxo-piperidine-1-yl)-6H- pyrano[2,3-ss]benz-2,1,3-oxadiazole) and
      levcromakalim were examined in vitro and in vivo. In isolated canine vascular
      beds, NIP-121 (3 x 10(-9) to 10(-7) M) and levcromakalim (3 x 10(-8) to 10(-6) M)
      produced a concentration-dependent reduction in the vasoconstrictor responses to
      U46619. The effects were antagonized by glibenclamide, an ATP-sensitive potassium
      channel blocker. The maximal relaxation was more than 70% of the maximal
      vasodilation induced by papaverine (10(-4) M), except in the basilar artery.
      These compounds had very potent effects on the coronary and cranial mesenteric
      arteries and saphenous vein. In the coronary perfused rat heart, both compounds
      (10(-7) M) also increased coronary perfusion flow. The effects were also
      inhibited by glibenclamide (10(-6) M). In anesthetized dogs, NIP-121 (1 to 10
      micrograms/kg (3.2 to 32 nmol/kg), i.v.) and levcromakalim (3 to 30 micrograms/kg
      (10.5 to 105 nmol/kg), i.v.) dose-dependently increased coronary and renal blood
      flow. NIP-121 and levcromakalim at higher doses produced the greatest increase in
      coronary blood flow among the blood vessels examined, in spite of the hypotensive
      effect. In conclusion, NIP-121 and levcromakalim were similarly selective
      vasodilators on the canine isolated coronary and cranial mesenteric arteries and
      saphenous vein, and they selectively increased coronary blood flow in vivo. With
      respect to increasing the coronary blood flow, NIP-121 had a fourfold greater
      potency than levcromakalim. This effect might be related to the glibenclamide
      sensitive potassium channels.

PMID- 7563973
TI  - Gastroprotective activity of FRG-8813, a novel histamine H2-receptor antagonist,
      in rats.
AB  - FRG-8813 ((+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2- pyridyl]oxy
      (Z)-2-butenyl]acetamide) is a novel histamine H2-receptor antagonist with gastric
      antisecretory and gastroprotective activities. The present study was designed to
      investigate the property of gastroprotective action. The oral ED50 values for
      inhibition of mucosal lesions against 1% NH3-, 60% ethanol in 0.15 N HCl-, 100%
      ethanol-, 0.6 N HCl- and sodium taurocholate in 0.4 N HCl-induced damage were
      3.3, 11.1, 14.9, 23.3 and 23.1 mg/kg, respectively. FRG-8813 was gastroprotective
      despite pretreatment with omeprazole, suggesting that the protective effect is
      independent of its antisecretory activity. It is unlikely that FRG-8813 works as
      a mild irritant because it showed a gastroprotective effect after intraperitoneal
      injection, but oral administration itself did not influence the rat gastric
      mucosa. Although pretreatment with indomethacin or N-ethylmaleimide did not
      affect the gastroprotection of FRG-8813, chemical deafferentation induced by
      capsaicin abolished the gastroprotection. Furthermore, prior administration of
      tetrodotoxin, the calcitonin gene-related peptide (CGRP) antagonist hCGRP or NG
      nitro-L-arginine attenuated the gastroprotection of FRG-8813 as well as that of
      capsaicin. In contrast to capsaicin, repeated administration of FRG-8813 neither
      enhanced the susceptibility of the mucosa to damage nor affected the
      gastroprotective action of short-term treatment. In conclusion, these results
      suggest that FRG-8813 has gastroprotective activity independently of acid
      antisecretory activity and that capsaicin-sensitive nerves may be partially or
      fully involved in the gastroprotective mechanisms of FRG-8813.

PMID- 7563974
TI  - Effects of sematilide, a novel class III antiarrhythmic agent, on action
      potential in guinea pig atrium.
AB  - Electrophysiological effects of sematilide, a novel class III antiarrhythmic
      agent, were examined and compared with those of (+/-)sotalol in guinea pig left
      atrium by a conventional microelectrode technique. Application of 0.1-1000 microM
      sematilide or 1-1000 microM (+/-)sotalol concentration-dependently prolonged the
      duration of action potentials (APD) that were elicited by electrical stimulation
      at 1 Hz. Other parameters of action potentials such as the maximum upstroke
      velocity of phase 0 depolarization, action potential amplitude and resting
      membrane potential were not affected significantly by these drugs in the
      concentration ranges employed. The prolongation of APD by sematilide or (+/
      )sotalol was accompanied by a corresponding increase in the effective refractory
      period (ERP). Approximately a 30% increase in ERP was obtained by the treatment
      with 5 microM sematilide or 100 microM (+/-)sotalol, suggesting that sematilide
      as a class III antiarrhythmic agent is approximately 20 times more potent than
      (+/-)sotalol on a molecular basis. When the stimulation rate was increased
      stepwise from 0.2 to 2 Hz, the relative increase in APD at 90% repolarization by
      the treatment with sematilide and (+/-)sotalol was slightly larger at 2 Hz than
      at 0.2 Hz, indicating that "reverse rate-dependence" was not observed under these
      conditions. These results may suggest a possibility that sematilide effectively
      blocks atrial arrhythmia.

PMID- 7563975
TI  - Impairment of endothelium-dependent relaxation by diesel exhaust particles in rat
      thoracic aorta.
AB  - Nitric oxide released from vascular endothelium plays important regulatory roles
      in cardiovascular and pulmonary systems. Epidemiological studies suggest that
      diesel exhaust particles (DEP) seem to be one of the causative factors
      responsible for the recent increase in pulmonary diseases. To clarify the
      pathogenic mechanism, the effects of DEP on vascular endothelial functions were
      investigated in terms of endothelium-dependent relaxation. Ring preparations of
      rat thoracic aorta were preincubated for 10 min with a DEP suspension (1, 10, 100
      micrograms/ml) at 37 degrees C in organ baths and relaxed with cumulative
      additions of acetylcholine following precontraction with phenylephrine (10(-6)
      M). The relaxation was attenuated by DEP-exposure in a concentration-dependent
      manner. An addition of superoxide dismutase (SOD) completely abolished the
      inhibitory effect of DEP at lower concentrations, but only partially at the
      higher concentration. DEP (10 micrograms/ml) neither affected the contractile
      response to phenylephrine in intact aortic rings nor the endothelium-independent
      relaxation by sodium nitroprusside in denuded rings, while DEP (100
      micrograms/ml) significantly attenuated both responses. These results suggest
      that 1) inhaled DEP causes pulmonary inflammation by inhibiting the endothelial
      formation and/or the effect of nitric oxide and 2) SOD reduces the adverse
      effects.

PMID- 7563976
TI  - Effect of E5324, a novel inhibitor of acyl-CoA:cholesterol acyltransferase, on
      cholesteryl ester synthesis and accumulation in macrophages.
AB  - The in vitro potencies of a novel inhibitor of acyl-CoA:cholesterol
      acyltransferase (ACAT), E5324 (n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1
      yl)propoxy]-6- methylphenyl]urea), were studied. E5324 was found to be a potent
      ACAT inhibitor in microsomes from a various tissues and in cultured cell
      homogenate, with IC50 values in the range of 0.044 to 0.19 microM. The kinetic
      study on E5324 showed that the inhibition of rat intestine ACAT was competitive
      with respect to oleoyl CoA. E5324 inhibited [3H]olate incorporation into
      cholesteryl [3H]oleate in phorbol ester-treated THP-1 cell lines (IC50 = 0.44
      microM). The rate of [3H]oleate incorporation into phospholipids and
      triglycerides was not affected by E5324. In an experiment with [3H]cholesterol as
      the substrate for ACAT, E5324 also inhibited [3H]cholesteryl ester synthesis
      (IC50 = 0.41 microM). Furthermore, E5324 prevented accumulation of both
      esterified and total cholesterol in acetyl low density lipoprotein-loaded THP-1
      cells. These results indicate that E5324 is a potent and selective ACAT inhibitor
      and prevents cholesteryl ester accumulation in macrophages.

PMID- 7563978
TI  - Role of GABAergic systems in the development of morphine tolerance in formalin
      treated mice.
AB  - Since the development of tolerance to morphine antinociception in formalin
      treated mice was delayed and diazepam normalized the delay, the involvement of
      GABAergic systems in the process was investigated. Gamma amino-n-butyric acid
      (GABA) at 10 mg/kg and the GABAA-receptor agonist muscimol at 0.05 mg/kg, i.p.,
      30 min before daily morphine injection at 10 mg/kg, s.c. completely reversed the
      delay in the development of morphine tolerance in the formalin-treated mice. The
      GABAA antagonist bicuculline at 1 mg/kg and the Cl(-)-channel blocker picrotoxin
      at 1 mg/kg extinguished the reverse effect of muscimol and GABA, respectively. In
      contrast, the GABAB antagonist CGP 35348 (3-aminopropane-diethoxymethyl
      phosphinic acid) up to 100 mg/kg, i.p. failed to abolish the GABA effect; and
      baclofen, a GABAB-receptor agonist, at 0.5 and 2 mg/kg, i.p., 30 min before
      morphine was without effect on the delay. On the other hand, bicuculline was
      incapable of abolishing the reverse effects of diazepam on the delay of tolerance
      development; and likewise, the reverse effect of muscimol was not affected by
      flumazenil. No appreciable influence of these GABA-related compounds was seen on
      morphine antinociception itself nor the development of tolerance in normal mice.
      These results suggest that the benzodiazepine-GABAA-Cl- channel complex is
      involved in the mechanism underlying the delay of the development of morphine
      tolerance in formalin-treated mice; however, it is deduced that benzodiazepine
      receptor and GABAergic systems are not always functionally coupled to each other
      in the mechanisms.

PMID- 7563977
TI  - Anti-thrombotic activity of KBT-3022 in experimental models of thrombosis.
AB  - In this study, we investigated the effects of KBT-3022 (ethyl 2-[4,5-bis(4
      methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate) , a potent and long-lasting anti
      platelet agent, in several experimental thrombosis models and compared them with
      those of other anti-platelet drugs. Oral administration of KBT-3022 prevented
      arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with
      respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of
      acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022,
      and ticlopidine hydrochloride (TP) showed no such effect in these models. In a
      guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus
      formation on a silk thread inserted into the shunt was dose-dependent and 300 and
      30 times more potent than the inhibition obtained with ASA and indomethacin,
      respectively. In a model of aortic thrombosis induced by perivascular application
      of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus
      formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had
      no effect. However, in a stasis-induced venous thrombosis model in guinea pigs,
      TP inhibited thrombus formation significantly, but KBT-3022 and ASA were
      ineffective. These results suggest that KBT-3022 may be a useful drug for the
      treatment and/or prophylaxis of thrombus formation in shunts and aortic
      thrombosis.

PMID- 7563979
TI  - Effects of KW-3902, an adenosine A1-receptor antagonist, on ascites volume in
      puromycin aminonucleoside (PAN)-induced nephrotic rats.
AB  - We investigated the effects of KW-3902 (8-(noradamantan-3-yl)-1,3
      dipropylxanthine), a potent adenosine A1-receptor antagonist, on the nephrotic
      edema induced by puromycin aminonucleoside (PAN; 100 mg/kg, i.v.) in rats. The
      treatment with PAN decreased urine volume and urinary excretions of sodium and
      potassium, resulting in the ascites formation in 7 days. In rats with the
      nephrosis, KW-3902 (0.01-1 mg/kg/day for 3 days, p.o.) showed diuretic effects
      and reduced the volume of ascites, as was the case with furosemide (30 mg/kg/day)
      and trichlormethiazide (1 mg/kg/day). These results suggest that even in the
      nephrotic state, the adenosine A1-receptor antagonist can be an effective
      diuretic to ameliorate edema.

PMID- 7563981
TI  - Differential effects of microtubule inhibitors on axonal branching and elongation
      of cultured rat hippocampal neurons.
AB  - We investigated the effects of microtubule inhibitors, taxol and colchicine, on
      the axonal branching and elongation in cultured rat hippocampal neurons. Taxol
      (50 nM) did not affect the morphology of neurons cultured under the control
      conditions, but significantly reduced the axonal branching stimulated by basic
      fibroblast growth factor. The axonal elongation stimulated by astrocyte
      conditioned medium was not affected by the same concentration of taxol.
      Colchicine (10 nM) showed similar effects as taxol. These results suggest that
      microtubules play more important roles in axonal branching than in axonal
      elongation.

PMID- 7563980
TI  - Vasopressin V1-receptor stimulation produces a positive inotropic response
      without affecting pHi in guinea pig papillary muscles.
AB  - Effects of arginine-vasopressin (AVP) on the contractile force, action potential
      (AP) and intracellular pH (pHi) were studied in isolated guinea pig papillary
      muscles using conventional and ion-selective microelectrode techniques. AVP
      increased the developed tension and the resting tension, and these responses were
      attenuated by the V1-receptor antagonist OPC-21268 (1-(1-[4-(3
      acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2 (1H)- quinolinone).
      However, AVP failed to affect AP configuration or pHi. These results suggest that
      AVP produces a positive inotropy by mechanism(s) other than intracellular
      alkalinization.

PMID- 7563982
TI  - Centrally applied bombesin increases nerve activity of both sympathetic and
      adrenal branch of the splanchnic nerves.
AB  - We reported that centrally applied bombesin probably excites both the gastric
      sympathetic and adrenomedullary systems and thus induces inhibition of gastric
      acid secretion. In the present study, therefore, we examined whether or not
      centrally applied bombesin directly affects sympathetic nerve activities in rats
      anesthetized with urethane. Intracerebroventricular administration of bombesin
      (0.3 and 3.0 nmol) increased discharge rates of the sympathetic branch as well as
      those of the adrenal branch of preganglionic greater splanchnic nerves. These
      effects were not secondary to changes in arterial blood pressure by bombesin. In
      conclusion, centrally applied bombesin directly activates both the sympathetic
      and adrenomedullary systems.

PMID- 7563983
TI  - Hypoxia and reoxygenation-induced injury of renal epithelial cells: effect of
      free radical scavengers.
AB  - The aim of this study was to characterize injuries of LLC-PK1 and MDCK cells
      exposed to hypoxia and reoxygenation. Exposure of LLC-PK1 cells to hypoxia
      reduced the ATP contents and increased the leakage of lactate dehydrogenase
      (LDH), but MDCK cells had no such injuries. Hypoxia-reoxygenation of LLC-PK1
      cells dramatically increased LDH leakage, which was suppressed by free radical
      scavengers, N,N'-diphenyl-p-phenylenediamine, superoxide dismutase and N,N'
      dimethylthiourea. These results suggest that use of LLC-PK1 cells has advantages
      for the investigation of ischemia-reperfusion injury of the kidney as an in vitro
      model and that generation of oxygen radicals is involved in the cellular injury
      induced by hypoxia-reoxygenation.

PMID- 7563984
TI  - [Construction of a scale for independent and interdependent construal of the self
      and its reliability and validity].
AB  - A hypothetical model about person's independent and interdependent construal of
      the self was proposed, based on the theories proposed by Markus and Kitayama
      (1991), Triandis (1989) and Yamaguchi (1994). The purpose of this study was to
      construct a scale for measuring individual difference on the independent and
      interdependent construal of the self and to examine its reliability and validity.
      Four hundred and ninety-four subjects (180 males and 314 females) responded to a
      questionnaire. Sixteen items were selected for the scale through item analysis.
      This scale showed one-factor structure and a high reliability. As for the
      construct validity, the scale showed significant correlations with Collectivism
      scale, Need for Uniqueness scale and Public Self-Consciousness scale. These
      results supported the hypothetical model about independent and interdependent
      construal of the self.

PMID- 7563985
TI  - [Uniqueness seeking behavior as a self-verification: an alternative approach to
      the study of uniqueness].
AB  - Uniqueness theory explains that extremely high perceived similarity between self
      and others evokes negative emotional reactions and causes uniqueness seeking
      behavior. However, the theory conceptualizes similarity so ambiguously that it
      appears to suffer from low predictive validity. The purpose of the current
      article is to propose an alternative explanation of uniqueness seeking behavior.
      It posits that perceived uniqueness deprivation is a threat to self-concepts, and
      therefore causes self-verification behavior. Two levels of self verification are
      conceived: one based on personal categorization and the other on social
      categorization. The present approach regards uniqueness seeking behavior as the
      personal-level self verification. To test these propositions, a 2 (very high or
      moderate similarity information) x 2 (with or without outgroup information) x 2
      (high or low need for uniqueness) between-subject factorial-design experiment was
      conducted with 95 university students. Results supported the self-verification
      approach, and were discussed in terms of effects of uniqueness deprivation,
      levels of self-categorization, and individual differences in need for uniqueness.

PMID- 7563986
TI  - [A study of the suggestibility effect on eyewitness testimony: discussion on the
      integration and the coexist hypothesis].
AB  - The purpose of the present study was to examine whether or not the eyewitness
      suggestibility effect might be obtained with a recognition memory and a source
      monitoring test, when an original event consisted of many pictures. In this
      source-monitoring test subjects identified the source of their memories. Results
      showed that the suggestibility effect was obtained in the recognition memory but
      not in the source-monitoring test, suggesting that misleading postevent
      information did not impair memory of the original event. The results also
      indicated that the eyewitness suggestibility effect might be caused by misled
      subjects' decision rather than their integrated memory representation.

PMID- 7563987
TI  - [A measurement scale for the Type A behavior pattern in women: the development of
      the Everyday Behavior Questionnaire].
AB  - A new 23-item scale, the Everyday Behavior Questionnaire (EDBQ) was developed to
      assess the Type A behavior pattern in women. Nurses (N = 139) in an university
      hospital participated in the validation study. Factor analysis of the 23 items
      revealed a four-factor structure. The four factors were anger/impatience,
      competitiveness/hard-driving, speed, and eagerness/interest. Internal consistency
      reliability estimates of four factors were adequate. Concurrent validity assessed
      by the relationship between the EDBQ and the Jenkins Activity Survey was
      significantly high. The four-factor structure and the relationship between the
      factors and psychological/physical symptoms adequately demonstrated Type A
      characteristics, as well as the uniqueness of the new questionnaire. These
      results suggested that the construct validity was in the desired direction.
      Further reliability and validity researches with the EDBQ in various samples were
      suggested.

PMID- 7563988
TI  - [The effects of the modes of task-oriented verbalization and the attractiveness
      of the tempting-objects on the kindergarteners' waiting behavior].
AB  - The purpose of the present study was to investigate the effects of overt and
      covert task-oriented verbalizations on kindergarteners' waiting behavior in the
      situation where the attractiveness of games was varied. One hundred and twenty
      kindergarteners, 4-6 years olds, were prohibited to touch the games while they
      were waiting for the experimenter who was out of the room to come back. High and
      low attractive situations were set by manipulating the attractiveness of games.
      In each situation, three treatment conditions were used: overt task-oriented
      verbalization, covert task-oriented verbalization, and no verbalization
      conditions. Subjects under the verbalization conditions were asked to respond to
      the buzzer signals during the waiting period by saying "don't touch the games"
      either aloud (overt condition) or silently moving lips (covert condition).
      Transgression latency was used to measure the effect of verbalization on waiting
      behavior. The results were as follows: (1) The overt task-oriented verbalization
      was effective in the low attractive situation, but not in the high attractive
      situation. (2) The covert task-oriented verbalization was not effective in both
      the high and low attractive situations.

PMID- 7563989
TI  - [The influences of self-evaluation level and items evaluation on test-retest
      effect: application of temporal comparison theory].
AB  - To examine the influences of items evaluation and self-evaluation on test-retest
      effect, which was first pointed out by Windle (1954) as the influence of prior
      test experience, a self-evaluative consciousness scale was repeatedly
      administered to 174 female college students. They were divided into an-hour, a
      month, and a-year conditions by intervals of tests. Thirty items of the scale
      were classified into five levels according to the size of evaluation factor
      loading. Findings were as follows: 1) Test-retest effect appeared in the group of
      a-month interval condition, 2) only for the items belonging to the lowest level
      of evaluation, 3) and this effect was mainly caused by the subjects whose self
      evaluative consciousness was not high. Results were discussed in terms of
      temporal comparison theory proposed by Albert (1977), which states that making an
      assessment of present self character, a person compares it with his or her past
      assessment mainly on inferior traits (items), unconsciously trying to raise self
      evaluation through responding to these items more positively. This mechanism is
      supposed to be driven by the motivation of evaluation maintenance.

PMID- 7563990
TI  - [The differences between individualists and cooperators: interpersonal cognition
      of resource allocation].
AB  - The purpose of this article is to study interpersonal cognition of resource
      allocation and individual differences in the cognition. Sixty subjects
      participated in an experimental game, and 18 individualists and 16 cooperators
      were selected according to their tendency in resource allocation, which is called
      social values. Then, they rated resource allocating behavior. Major findings were
      as follows: (1) Both groups rated "allocating more resource to the partner" as
      more socially desirable and friendly. (2) Individualists rated "allocating more
      resource to self," which was consistent with their social values, as more
      socially desirable. They also rated "equal allocation with own resource adjusted"
      as more socially desirable but less dynamic. (3) Cooperators rated "equal
      allocation with own resource adjusted," which was consistent with their social
      values, as more socially desirable and friendly. (4) Both groups rated "more
      resource to self" and "less resource to the partner" as dynamic (active and
      assertive). The relation between interpersonal cognition and social values is
      discussed.

PMID- 7563991
TI  - [Texture segregation in large visual field].
AB  - Using large texture stimuli (72 degrees x 72 degrees or 20 degrees x 20 degrees),
      we investigated spatial properties of texture segregation. In Experiment 1, we
      used L-like forms, T-like forms, or tilted T-like forms to create a large
      background texture field, in which a small target region of the odd forms was
      embedded. The texture display was presented for 255 ms, and subjects were asked
      to detect the target and to recall its position. The target upright Ts in the
      tilted Ts and the target tilted Ts in the upright Ts segregated easily. In
      contrast to our expectation, however, the target upright Ts in the Ls and the
      target Ls in the upright Ts were detected better in the periphery than in the
      central area. In Experiment 2, subjects were asked to detect a single target
      element embedded in the background. The size of the elements was enlarged to that
      of the target texture region in Experiment 1. The target Ts and Ls were detected
      better in the central area than in the periphery. These results can be explained
      by the differential grouping processing and distribution of attention in the
      visual field.

PMID- 7563992
TI  - [Serum phospholipase A2 activity in patients with aspirin-induced asthma].
AB  - Urinary excretion of leukotrienes is greater in patients with aspirin-induced
      asthma (AIA) than in other patients with asthma in remission, and is greater
      still during an aspirin-induced attack. We therefore hypothesized that increased
      phospholipase A2 (PLA2) activity leads to increased leukotriene synthesis when
      non-steroidal antiinflammatory drugs inhibit cyclooxygenase in patients with AIA,
      and that PLA2 activity increases further during an aspirin induced attack. To
      test this hypothesis, we measured the serum PLA2 activity in adult asthmatic
      patients, and compared the activity in those with AIA to the activity in those
      without AIA. The subjects were 43 patients with asthma in remission, 17 with AIA
      and 26 without AIA. Serum PLA2 activity was also measured before and after
      intravenous administration of lysine-aspirin in three patients with AIA and in
      one without AIA. Serum PLA2 activity was measured by radioimmunoassay. Serum PLA2
      activity in patients with AIA, in those without AIA, and in healthy controls was
      300.9 +/- 52.9, 294.4 +/- 65.3 and 171.7 +/- 41.8 pmol/ml/min, respectively.
      Serum PLA2 activity in asthmatic patients was significantly higher than in
      healthy controls (p < 0.01), but there was no difference between patients with
      and without AIA. Intravenous lysine-aspirin provoked asthmatic attacks in three
      patients with AIA. However, intravenous lysine-aspirin did not significantly
      change serum PLA2 activity in the three patients with AIA or in the patient
      without AIA. These results indicate that although PLA2 may be involved in the
      pathogenesis of bronchial asthma, it is not specific to AIA. Thus, the
      pathophysiology of AIA remains unclear and further investigation is needed.

PMID- 7563993
TI  - [Clinical evaluation of the small solitary pulmonary nodule].
AB  - The diagnostic process for small solitary pulmonary nodules was retrospectively
      analyzed. Three hundred and forty-three patients, each with a solitary pulmonary
      lesion of less than 3 cm on chest radiography, were evaluated. The patients were
      seen at our hospital between September 1986 and December 1993. They consisted of
      138 with malignant diseases (114 with lung cancer and 24 with metastatic tumors),
      and 205 with benign diseases. There were 146 patients (71%) with benign lesions
      of less than 2 cm. The diagnosis in 118 patients (86%) with malignant disease was
      made by lung biopsy. Of these 118 patients, 19 underwent biopsy of the lung
      through a thoracoscope or open lung biopsy via a thoracotomy. Benign diseases
      were diagnosed in 167 patients (81%) by various laboratory tests and imaging
      techniques, including chest radiography. Thinsection CT was done in 132 patients.
      In 72 of these 132 patients (16 with lung cancer, 23 with metastatic tumors, and
      33 with benign tumors), a judgement regarding whether the lesion was malignant or
      not could not be made. Therefore, open lung biopsy was done in 5 patients. Twenty
      four patients were only observed, 43 underwent biopsy, and 35 underwent surgery.
      A decision tree needs to be established to select therapeutic options for
      management of patients whose diagnoses remain indeterminate even after thin
      section CT. Formulation of a decision tree based not only on clinical findings
      but also on the results of diagnostic imaging is necessary to improve clinical
      decision making regarding small solitary pulmonary nodules.

PMID- 7563994
TI  - [Efficacy of video thoracoscopic lung biopsy in diffuse lung diseases: comparison
      with open lung biopsy].
AB  - The efficacy and safety of video thoracoscopic lung biopsy (VTLB) and of open
      lung biopsy (OLB) were compared in patients with diffuse lung diseases. Thirty
      three patients who had undergone VTLB were retrospectively studied and compared
      with 67 patients who had undergone OLB. There were no significant differences in
      age (52.8 +/- 10.9 vs 53.4 +/- 10.3), in the number of biopsies per patient (2.6
      +/- 0.6 vs 2.7 +/- 0.6), or in the rate of diagnosis (94% vs 93%) between the two
      groups. However, the rate of diagnosis was low when the number of VTLB or OLB
      performed per patient was low. The patients undergoing VTLB had significantly
      shorter operative times (VTLB, 100.2 +/- 27.2 min. vs OLB, 119.8 +/- 42.6 min; p
      < 0.01) and less blood loss (VTLB, 4.7 +/- 14.6 ml vs OLB, 65.7 +/- 77.0 ml; p <
      0.001). Complications occurred in 3 of the 33 who underwent VTLB, and in 18 of
      the 67 who underwent OLB. These results indicate that VTLB is an effective and
      safe alternative in the diagnosis of diffuse lung diseases.

PMID- 7563995
TI  - [Clinical features of subacute interstitial pneumonia--clinico-pathological study
      based on open lung biopsy findings].
AB  - A clinico-pathological study was done to elucidate characteristic features of
      subacute interstitial pneumonia. The patients were four men and mine women, with
      a mean age of 60 years. In ten patients, the disease was idiopathic, three had
      collagen vascular disease, (and one was undergoing gold therapy for rheumatoid
      arthritis). The time interval between onset of symptoms and open lung biopsy was
      80 +/- 40 days. Eleven patients had progressive dyspnea, seven had coughing, and
      only one complained of fever. Fine crakles were heard in ten patients. Mild
      increases in CRP were observed in all cases. Mild increases in total serum IgG
      concentration were observed in five of eight cases. Multiple patchy infiltration
      or diffuse interstitial shadows, located predominantly in the lower fields of
      both lungs were the characteristic chest roentgenographic findings. The average
      %VC was 62.7 +/- 17% and the average PaO2 was 68.3 +/- 10 Torr. Bronchoalveolar
      lavage was done in nine patients, and the mean total cell count was 16.5 +/- 10.2
      x 10(4)/ml. A moderate increase in lymphocytes (30.8 +/- 18.6%) with a low CD4/8
      ratio (0.48 +/- 0.57), a mild increase in neutrophils (6.2 +/- 9.1%), and a mild
      increase in eosinophils (2.3 +/- 3.7%) were observed. Pathologically,
      interstitial cellulo-fibrous changes associated with alveolar space closure due
      to organization of exudate were the main features. Patients were given steroid
      pulse therapy or oral steroids. The results were mild to marked improvements in
      chest roentgenographic findings and lung function.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7563996
TI  - [Foamy alveolar macrophages in various lung diseases, and their origin in rabbit
      lungs].
AB  - The present studies were done to clarify the significance of foamy alveolar
      macrophages (FAM) in lung diseases, and the mechanism of the production of
      macrophages in rabbit lungs. Human subjects consisted of 18 normal volunteers
      (NV) and 47 patients with lung disorders: chronic bronchitis (CB), 7 cases;
      pulmonary fibrosis (PF), 8 cases; old pulmonary tuberculosis (OPT), 7 cases; lung
      cancer (LC), 20 cases; and bronchiectasis (BE), 5 cases. In each case, over 30
      macrophages in the BALF were observed by transmission electron microscopy. There
      were no significant differences in the percentage of FAm in the BALF among NV,
      CB, and PF. Furthermore, OPT and LC were not significantly different. Many more
      FAM were seen in OPT and LC than in NV, CB, and PF (p < 0.005). The percentage of
      FAM obtained from BE was much higher than that from OPT and LC (p < 0.005). These
      results suggest that the grade of foamy change in macrophages differs among lung
      diseases. Three groups of rabbits were studied. Group I rabbits (n = 6) were
      control, Group II rabbits (n = 6) underwent bronchial clamping, and Group III
      rabbits (n = 6) underwent complete replacement of blood with saline. The number
      of macrophages and type II cells was much greater in Group II rabbits than in
      Group I rabbits. In Group III rabbits, the number of macrophages was lower than
      in Group I rabbits. In Group III rabbits, vacuole-like structures were seen in
      the cytoplasma of type II cells, but not from in macrophages. These findings
      suggest that anoxia and blood flow are important for the appearance of
      macrophages in alveolar space. Group III rabbits had few alveolar macrophages.
      Therefore, alveolar macrophages may be derived from monocytes in blood.

PMID- 7563997
TI  - [Role of viral infections in acute exacerbation of idiopathic interstitial
      pneumonia].
AB  - To evaluate the possibility that viral infections can trigger acute exacerbations
      of idiopathic interstitial pneumonia (IIP), we analyzed data from 105 patients
      with IIP. Acute exacerbation was defined as an increase in dyspnea, a decrease in
      PaO2 by more than 10 Torr, and worsening of chest radiographic findings within
      one month. Viral infection was said to be involved when patients had more than a
      4-fold change in viral antibody titer or viral inclusion bodies in sputum during
      the acute exacerbation. Of the 105 patients with IIP, 30 had acute exacerbations.
      Among these 30 patients, viral infection was said to be involved in 11 (37%).
      Presumptive viruses were influenza virus (n = 6), parainfluenza virus (n = 1),
      herpes simplex virus (n = 1), RS virus (n = 1), and cytomegalovirus (n = 2). The
      levels of serum immunoglobulin A (IgA) before acute exacerbations were
      significantly lower (p < 0.05) in patients in whom viral infection was said to be
      involved. These results suggest that viral infection associated with a low value
      of serum IgA is an important trigger of acute exacerbations of IIP.

PMID- 7563998
TI  - [Acyclovir and guinea-pig airway smooth muscle].
AB  - Acyclovir, an anti-herpes virus drug, has been reported to affect aspirin-induced
      asthma (AIA). Acyclovir was reported to decrease the sensitivity to aspirin in
      some AIA patients. Although the hypothesis that AIA is related to viral infection
      has been stated, there is no proof that patients with AIA are infected with a
      specific virus. Therefore, whether the effect of acyclovir on AIA is due to an
      antiviral effect is not clear. We hypothesized that acyclovir directly affects
      airway smooth muscle. To test this hypothesis, we examined whether acyclovir can
      directly contract or relax guinea-pig airway strips, and whether it can modify
      contraction or relaxation induced with several agents in vitro. Acyclovir did not
      directly affect basal smooth muscle tone and did not affect the responses to
      leukotriene D4, prostaglandin E2, carbachol, or KCl. We conclude that acyclovir
      has no direct effect on the function of guinea-pig airway smooth muscle.

PMID- 7563999
TI  - [A case of systemic arterial supply to the normal left basal segments with
      anomalous return of the left inferior pulmonary vein].
AB  - A 38-year-old man was admitted to Yatsushiro General Hospital because of an
      abnormal shadow on chest X-ray film. Chest X-ray film showed a tumorous shadow in
      the left posterior basal segment (S10). Chest CT scan showed that this shadow was
      consisted of torutuous vessels and was connected to the descending thoracic
      aorta. Angiographic examinations showed that there was no normal left basal trunk
      of the pulmonary artery, and revealed an anomalous arterial supply to the basal
      segments from the descending thoracic aorta, with an anomalous left inferior
      pulmonary vein. The left bronchial tree appeared normal during fibroptic
      bronchoscopy (confirmed by post-operative bronchography). From these findings, we
      determined that this patient had an systemic arterial supply to the normal basal
      segments. Furthermore, this patient had an anomalous left inferior pulmonary
      vein, which took a peculiar route to the left atrium. The left lower lobe and the
      anomalous systemic artery were resected. In the resected specimen, the bronchi of
      the left lower lobe had a normal structure and showed a normal pattern of
      distribution. This anomalous systemic artery had an elastic component.

PMID- 7564001
TI  - [A case of interstitial pneumonia in polymyositis difficult to distinguish from
      gold pneumonitis].
AB  - Rheumatoid arthritis was diagnosed in a 48-year-old woman. She received a gold
      compound, and 4 weeks after the start of that therapy, interstitial pneumonia
      appeared. Findings from a muscle biopsy, and high serum CPK and LDH levels
      indicated that she suffered from polymyositis rather than rheumatoid arthritis.
      The result of a drug lymphocyte stimulation test (DLST) for the gold compound was
      more than 200%. Because the usefulness of the DLST for the gold compound in the
      diagnosis of gold pneumonitis is not thoroughly established, the DLST was also
      done in patients with rheumatoid arthritis who were receiving the gold compound
      without side effects, and in normal subjects. Many of the rheumatoid arthritis
      patients and some of the normal subjects had a positive response to the gold
      compound. Therefore a positive response on the DLST for the gold compound does
      not always support the diagnosis of gold pneumonitis.

PMID- 7564000
TI  - [A case of acute eosinophilic pneumonia: bronchoalveolar lavage findings before
      and after steroid treatment].
AB  - An 18-year-old woman presented with coughing, fever, progressive dyspnea, and
      diffuse infiltrates on the chest X-ray film. Analysis of bronchoalveolar lavage
      fluid showed 73% eosinophils. Acute eosinophilic pneumonia was diagnosed.
      Methylprenisolone, 1 g per day was given for three days and her condition
      improved dramatically. No relapse was observed. Analysis of bronchoalveolar
      lavage fluid also showed lymphocytosis, abnormally high concentrations of ECP, GM
      CSF, IL-5 and sICAM-1, and hypersegmentation of eosinophil nuclei. After steroid
      treatment almost all these findings returned to normal; only lymphocytosis
      remained. Precipitating antibodies against four kinds of fungi, including
      Trichoderma viridae, were noted in the serum, but the environmental provocation
      test was negative and those fungi were not detected in the environmental culture
      growth. Comparison of bronchoalveolar lavage findings obtained before and after
      steroid treatment can provide information on the mechanism of eosinophil
      accumulation in the lung. This case also draws attention to the relationship
      between acute and chronic eosinophilic pneumonia.

PMID- 7564002
TI  - [A case of slowly progressing interstitial pneumonia associated with idiopathic
      thrombocytopenic purpura].
AB  - A 72-year-old man had been taking 10 mg/day of prednisone since idiopathic
      thrombocytopenic purpura (ITP) was diagnosed when he was 60 years old. An
      interstitial lung shadow was observed on chest X-ray films when he was about 62
      years old, and interstitial pneumonia (IP) (chronic-type), etiology unknown was
      diagnosed. With the progression of honey-comb shadows on the dorsal side of the
      lower lung fields, cystic changes on the anterior side of the upper lung fields
      also became more obvious. Slowly progressing IP associated with ITP is very rare.
      In addition, the chest CT findings of cystic changes on the dorsal side in the
      lower lung fields and on the anterior side in the upper lung fields are quite
      interesting.

PMID- 7564003
TI  - [A case of post-traumatic arteriovenous fistula of the subclavian artery].
AB  - A 67-year-old woman was admitted to our hospital for a complete medical
      evaluation of a pulmonary nodule on a chest X-ray film, which was found during an
      annual check-up. A loud bruit was audible over the left chest and the
      supraclavicular region. Computerized tomography (CT) scan and magnetic resonance
      imaging revealed an arteriovenous fistula from a branch of the left subclavian
      artery into the paravertebral veins. Angiography disclosed that the arteriovenous
      fistula was fed by the left costocervical artery. Transarterial embolization of
      the arteriovenous fistula was done with 5 mechanical detachable coils and 2 micro
      coils. Postembolization angiography showed a marked decrease in blood flow and
      near-elimination of the arteriovenous fistula. The shrinkage of the arteriovenous
      fistula was also observed on CT scan. This patient had been in a traffic
      accident, and had been clinically well before the accident. Post-traumatic
      arteriovenous fistula was strongly suspected, because a pulmonary nodule on chest
      X-ray film and a bruit were found after a traffic accident.

PMID- 7564004
TI  - [Persistent reactive airway dysfunction syndrome after exposure to chromate].
AB  - A 42-year-old man was admitted to the hospital because of wheezing and dyspnea
      that began 20 minutes after accidental exposure to irritant gas containing
      chromate at a chrome pellet manufacturing plant. The patient had a positive skin
      reaction to chromite (Cr2O3). Reduction of FEV1.0 was observed 120 minutes after
      Cr2O3 inhalation challenge. By 150 minutes after Cr2O3 inhalation, FEV1.0 had
      decreased by 32%. Chest X-ray film revealed no abnormalities. Histological
      findings of the lung tissue obtained by open lung biopsy revealed bronchospasm
      and peri-bronchial inflammatory cell infiltration without bronchiolar
      obstruction, and thus bronchiolitis obliterans was ruled out. This patient
      fulfilled the criteria of reactive airway dysfunction syndrome (RADS) proposed by
      Brooks; onset of symptoms very soon after a single exposure to an irritant,
      persistence of asthmatic symptoms, obstructive pulmonary dysfunction, and the
      presence of airway hyperreactivity to methacholine. During the initial hospital
      stay, asthmatic symptoms were relieved by intensive anti-asthmatic treatment
      including oral and parenteral corticosteroids. However, the patient's asthmatic
      symptoms have lasted for eight years and necessitate the use of systemic
      steroids, and regular use of inhaled steroids and bronchodilators. We know of no
      previous reported case of RADS after chromate exposure.

PMID- 7564005
TI  - [A benign clear cell tumor of the lung that grew gradually over five years].
AB  - A 38-year-old man was found to have an abnormal shadow in his chest X-ray film
      during a general medical examination. A nodule with a homogeneous density and a
      clear margin was seen in the upper lobe of the right lung. Since this shadow
      gradually enlarged during a five-year follow-up period, he was admitted to our
      hospital. Chest contrast and dynamic CT scans and aortography showed
      characteristics of a benign tumor with somewhat rich vascularity. The doubling
      time of this tumor was about 430 days. Transbronchial brushing for cytologic
      study and a transbronchial biopsy showed no malignancy. However, the tumor was
      surgically resected because of its gradual growth over the five years. The
      resected tumor was histologically diagnosed as a benign clear cell tumor of the
      lung. This disease was first described by Leibow and Castleman in 1963, as a
      benign pulmonary tumor similar to metastatic renal cell carcinoma. This disease
      is extremely rare and only 61 cases have been reported: twenty cases, including
      the present case, in Japan and 41 in other countries.

PMID- 7564007
TI  - [A case of Legionella pneumonia successfully treated with roxithromycin].
AB  - A 56-year-old man was admitted to our hospital because of a high fever. An
      abnormal shadow was seen on his chest X-ray film. He was treated with
      piperacillin, isepamycin, and minocycline, but his fever remained and the
      abnormal shadow got worse. Because he had proteinuria, a severe headache,
      hyponatremia, and hypophosphatemia, Legionella pneumonia was suspected. A skin
      test for erythromycin was positive, so roxithromycin was given orally. By the
      next day the fever had remitted, the appearance of the chest X-ray film had
      improved, and his symptoms were promptly relieved. This case suggests that
      roxithromycin can be effective against Legionella pneumonia.

PMID- 7564006
TI  - [A case of cystic fibrosis in a Japanese student].
AB  - A 16-year-old boy was admitted to our hospital because of coughing, sputum, and
      exertional dyspnea. Seven months after birth cystic fibrosis had been diagnosed.
      The chest roentgenogram on admission showed diffuse reticulonodular shadows and
      overinflation. Pulmonary function tests revealed obstructive and restrictive
      impairment. Erythromycin and Lomefloxacin were administered by mouth, and
      aminoglycosides were administered by inhalation. His symptoms were alleviated,
      and he is now an outpatient. In Japan, cystic fibrosis is rare, and this patient
      is extremely rare because he has grown up to be a 16-year-old. In this case, low
      dose and long-term erythromycin administration was very effective.

PMID- 7564008
TI  - [A patient with cryptogenic organizing pneumonitis who presented with multiple
      patchy shadows].
AB  - A 62-year-old woman was admitted to our institution for abnormal shadows on a
      screening chest roentgenogram. An immunoelectrophoresis test on admission
      revealed a polyclonal gammopathy. In her bronchoalveolar lavage fluid, the
      percentage of lymphocytes was found to be high: 47%. These results indicated an
      abnormal immunological state. A chest X-ray film showed multiple patchy shadows
      in both lungs. A chest CT scan revealed that the shadows were distributed
      peripherally, and abutted the pleura. Before treatment, the lesions enlarged
      toward the hilum concentrically, and cleared from the pleural side. This change
      is characteristic of cryptogenic organizing pneumonitis. The pathological finding
      at open lung biopsy was organizing pneumonitis. Bronchiolitis obliterans was not
      pathologically recognized. The shadows on the chest X-ray film almost completely
      disappeared after treatment with predonisolone at a daily dose of 30 mg. We
      diagnosed this as a case of cryptogenic organizing pneumonitis with typical
      shadows.

PMID- 7564009
TI  - [A case of thymic enlargement with hyperthyroidism].
AB  - A case of thymic enlargement with hyperthyroidism is reported. Hyperthyroidism
      was diagnosed in an 18-year-old woman, and a chest roentgenogram showed an
      anterior mediastinal mass. The mass had shrunk after anti-thyroid medication was
      given. This patient was thought to have thymic hyperplasia associated with
      hyperthyroidism.

PMID- 7564011
TI  - [Valve repair or valvulectomy without replacement for infective endocarditis: a
      report of 11 cases].
AB  - Recently advances in early diagnosis of infective endocarditis (IE) by
      echocardiography provide for IE as a target disorder for valve repair.
      Valvulectomy without replacement might be still better operation of choice for
      some cases of intractable right-sided endocarditis. For our experience in 11
      cases of valve repair or valvulectomy without replacement for IE, actuarial
      survival and reoperation-free rate at 6.8 years of mean follow-up after surgery
      was 81.8% and 90.9%. Persistent infection and intraoperative evaluation of the
      residual regurgitation was the point for postoperative management after these
      procedures. Although an elaborative valve repair should be applied for right
      sided endocarditis, total pulmonary valvulectomy or regional tricuspid
      valvulectomy without prosthesis was available for destructive endocarditis.

PMID- 7564010
TI  - [Surgical treatment of the true aortic arch aneurysm combined with coronary
      artery disease].
AB  - Between January 1989 and August 1994, 6 patients with true transverse aortic arch
      aneurysm combined with coronary artery disease (CAD) were operated in our
      institute. They had the simultaneous revascularization for both lesions. There
      were no cardiac deaths at early and late result. The present data suggested that
      the patient who underwent successful coronary artery bypass grafting have the
      same risk for transverse aortic arch aneurysm operations as the patients without
      CAD.

PMID- 7564012
TI  - [Citrate and ionized calcium on extracorporeal circulation in pediatric cardiac
      surgery].
AB  - The control of optimum concentrations of ionized calcium Ca2+ during
      cardiopulmonary bypass is important in maintaining cardiac function and reducing
      reperfusion injury. Ca2+ may be in part dependent upon the serum level of citrate
      Cit in use of hemodiluted prime in pediatric cardiac surgery. The purpose of this
      study was to ascertain fluctuations of Ca2+ during bypass in relation to Cit and
      to study control of optimum Ca2+. Ca2+ and Cit was measured prior to and every 10
      or 20 minutes during bypass in 12 children aged 21 days to 6 years. Of 6 patients
      (body weight less than 6 kg) received acid-citrate-dextrose (ACD) solution 20 ml
      before aortic declamp to give low Ca2+ for reducing reperfusion injury. Ca2+
      showed initial drop and then gradually increased as the result of decreasing Cit.
      Ca2+ was inversely correlated with Cit (r = 0.85, p = 0.0001). When ACD 20 ml was
      added, Ca2+ significantly decreased from 1.00 +/- 0.13 to 0.65 +/- 0.13 mmol/l.
      However, Cit remained 24.3 +/- 13.3 mg/dl at the end of bypass. In conclusion,
      the results of this study suggest that gradually increasing Ca2+ during bypass
      may be related to the rate of citrate metabolism and the use of citrate for the
      control of Ca2+ remains questionable.

PMID- 7564013
TI  - [Anomalous origin of the right pulmonary artery from the ascending aorta: a case
      report].
AB  - We report a successful case of anomalous origin of the right pulmonary artery
      from the ascending aorta. A 34 days old infant, who had suffered from cardiogenic
      shock, underwent a direct anastomosis of the right pulmonary artery to the main
      pulmonary artery behind the ascending aorta under cardiopulmonary bypass.
      Postoperative catheterization showed no significant stenosis over the anastomosis
      and normalized pulmonary artery pressure. We conclude that early surgical
      correction is necessary in the treatment of this life threatening disease.

PMID- 7564014
TI  - [Continuous measurement of myocardial oxygen saturation using near-infrared
      spectroscopy during warm blood cardioplegia].
AB  - Continuous infusion of warm blood cardioplegic solution is often interrupted
      during coronary artery bypass grafting to obtain a bloodless operating field. We
      measured myocardial oxygen saturation continuously using near-infrared
      spectroscopy to determine myocardial oxygen metabolism during intermittent warm
      blood cardioplegia (IWBC). In 7 adult mongrel dogs undergoing cardiopulmonary
      bypass IWBC was administered using the Buckberg-Shiley system. Cardiac arrest was
      induced by a warm blood cardioplegic infusion of 100 ml/min for 5 minutes
      followed by a maintenance infusion of 40 ml/min for 5 minutes. The infusion of
      warm blood cardioplegia was then stopped for 15 minutes. Measurement of
      myocardial oxygen saturation was performed continuously throughout
      cardiopulmonary bypass. IWBC produced an increase in myocardial oxygen saturation
      for the first 5 minutes and a slight decrease for the second 5 minutes. After the
      termination of IWBC, myocardial oxygen saturation showed a marked reduction for 3
      minutes and plateaued after 5 minutes. Measurement of myocardial oxygen
      saturation revealed myocardial oxygen metabolism during IWBC. This procedure may
      be a useful way to monitor myocardial oxygen metabolism during open heart
      surgery.

PMID- 7564015
TI  - [An operative case of the dumbbell type retromediastinal schwannoma].
AB  - Neurogenic tumors of the mediastinum with an intraspinal component connected by a
      narrowed segment in the intervertebral one are generally described as dumbbell or
      hour-glass tumors, which need cautious and precise diagnoses and remedies,
      compared with other neurological tumors. A 62-year-old male was admitted to our
      hospital for abnormal tumor shadow in the chest X-ray film. We diagnosed this
      case as dumbbell type neurogenic tumor by MRI and CT. An operation was performed
      by modified Grillo's method: One-stage operation. With patient in prone position,
      L-shaped skin incision was made. Through total laminectomy of T-5 and T-6 and
      resection of the 6th rib, paravertebral portion of the tumor was removed, and
      thoracotomy in the same position under the same view enabled us to remove the
      residual tumor. Histopathological diagnosis was schwannoma. After the operation,
      no neurological complications were detected.

PMID- 7564016
TI  - [Two cases of CA19-9 producing pulmonary papillary adenocarcinoma].
AB  - Two cases of CA 19-9 producing pulmonary papillary adenocarcinoma were reported.
      Pathological examination showed a well differentiated papillary adenocarcinoma
      with partially bronchiolo-alveolar cell type. Immunohistochemical study showed a
      positive straining for CA 19-9 on tumor cells. The level of CA 19-9 decreased
      after lobectomy and anti-cancer chemotherapy using CDDP and VDS. The series of CA
      19-9 level is very useful to evaluate the effect of surgery and chemotherapy.
      Also it is useful to find out the recurrence of carcinoma.

PMID- 7564017
TI  - [Long-term results of Bentall and modified Bentall procedure in aortic root
      replacement].
AB  - Between 1976 and 1994, sixteen patients who had annulo-aortic ectasia required
      aortic root replacements. Ten patients had annulo-aortic ectasia and 6 patients
      had aortic dissections. The operative techniques included Bentall procedure in 6,
      Cabrol procedure in 3 and Carrel patch procedure in 7. No hospital death was
      noted, although there were three major late complications and two of them died.
      First patient having Bentall procedure died from acute myocardial infarction
      because of the compressed left coronary artery by the wrapping aneurysmal wall.
      Second patient having Bentall procedure had enlargement of residual false lumen.
      Third patient having Cabrol procedure developed false aneurysm at the ostial
      anastomosis and died of cerebral haemorrhage. In contrast, no late complication
      has been noted in patients having Carrel patch procedure. Although further long
      term follow-up is required, our experience suggests that Carrel patch procedure
      has less late complication.

PMID- 7564018
TI  - [Coronary artery bypass grafting in cases with the atherosclerotic ascending
      aorta].
AB  - Among 172 cases of coronary artery bypass grafting, 9 cases (5%) revealed
      severely atherosclerotic ascending aorta. In 3 of the 9 cases, total aortic cross
      clamping in the distal anastomoses of saphenous vein graft (SVG) and partial
      aortic clamp in the proximal anastomoses of SVG were performed. In 1 case with
      this technique, cerebral infarction was occurred. In 4 cases, total aortic cross
      clamping in the distal and proximal anastomoses of SVG was performed. In 2 of
      these cases with this technique, cerebral infarctions were occurred. Hypothermic
      circulatory arrest was performed in 2 of the rest. In one case that was predicted
      to have atherosclerosis of ascending aorta prior to operation, the left internal
      thoracic artery was anastomosed to the left anterior descending, and SVG to the
      right coronary artery with hypothermia and ventricular fibrillation. And during
      the proximal anastomoses of SVG, hypothermic circulatory arrest without aortic
      clamping was initiated. In another case, atherosclerosis of ascending aorta was
      noted after aortic cross-clamping. Then the aorta was declamped, hypothermic
      circulatory arrest was established, the aorta was opened, the diseased segment
      was resected, and proximal anastomoses of SVG was performed to Dacron patch which
      was implanted for aortic wall. There were no cerebral infarction in last two
      patients.

PMID- 7564019
TI  - [Two case reports of Stanford type A acute aortic dissection complicated with
      thrombosed false lumen and saccular aneurysm formation].
AB  - We report two cases of successful surgical treatment for Stanford type A aortic
      dissection with thrombosed false lumen and saccular aneurysm formation. They were
      admitted to our clinic for severe anterior chest and back pain. Diagnosis was
      made as a Stanford type A dissection with thrombosed false lumen by chest CT,
      aortography and cardiac ultrasonography. Aortography showed ulcer like projection
      (ulp) in the ascending aorta, although flow in false lumen was not visualized.
      They were initially treated with antihypertensive drugs. Six and eight weeks
      later, although medical therapy was continued, a saccular aneurysm of the
      ascending aorta was found to be increased in size rapidly in both cases.
      Operation performed was the ascending aorta replacement with resection of the
      saccular aneurysm. The location of the ulp was found to be corresponded with the
      intimal tear at surgery. The postoperative courses were uneventful. Thus, careful
      medical follow up and surgical treatment were necessary in these cases. We
      believe that the ulp represents defect in the intima leading to the clotted false
      lumen and provides a possible sign of rupture in clinical course of aortic
      dissection.

PMID- 7564020
TI  - [A case of pulmonary arteriovenous fistula failed in transcatheter embolization
      and followed by emergency operation].
AB  - We reported a 55-year-old male case with pulmonary arteriovenous fistula. The
      lesion existed in right S9b and was about 6 cm in diameter. The afferent artery
      and the efferent vein, both were more than 10 mm in diameter, were shown on the
      chest CT and DSA film. At first transcatheter embolization with steel coils and
      Histoacryl was tried. Though we succeeded in embolization of the afferent artery,
      embolization of the fistula was failed because of reflux from the drainage vein.
      And a coil, a fragment of Histoacryl dropped and floated in the fistula. With
      concerning about the risk of embolization of the other organ with these
      materials, we performed the enucleation of the fistula at the next day. Although
      transcatheter embolization is useful in treating pulmonary arteriovenous fistula,
      in the case of wide communication with large drainage vein such as our case, it
      seems to be risky.

PMID- 7564021
TI  - [A case report of tracheal stenosis due to true aortic arch aneurysm of
      retroesophageal right aortic arch associated with so called vascular ring-facial
      syndrome].
AB  - A 63-year-old man admitted to our hospital because of dyspnea and inspiratory
      stridor. The X-ray computed tomography and angiogram revealed tracheal stenosis
      due to compression by aortic arch aneurysm of retroesophageal right aortic arch.
      His face was congenitally asymmetrical, and he also showed anotia, and meatal
      atresia. In the operation, we approached the aneurysm via median sternotomy and
      left thoracotomy by the 3rd intercostal space, and found atretic left aortic arch
      in front of trachea. So, operative diagnosis was Edwards Ib complete vascular
      ring associated with right aortic arch aneurysm. The aneurysm was incised and the
      arch and its branches were reconstructed with vascular prosthesis under ECC using
      selective cerebral perfusion. Postoperatively, until 5th postoperative day his
      condition was uneventful, and he was neurologically almost normal. But on the 5th
      postoperative day, his hemodynamics suddenly deteriorated because of severe
      pneumonia and septicemia. On the 6th postoperative day, he died in spite of
      earnest resuscitation. We could not find any previous reports about this rare
      combination of diseases.

PMID- 7564022
TI  - [A case of tricuspid regurgitation due to blunt chest trauma].
AB  - A case of tricuspid regurgitation due to blunt chest trauma is presented. A 35
      year-old man was in good health until he sustained blunt chest trauma in a
      traffic accident 17 years ago (in 1972). After that easy fatiguability developed.
      In 1977, slight tricuspid regurgitation was detected, but he was clinically well
      and no treatment seemed necessary. In October 1989, he was admitted due to right
      heart failure. The chest X-ray film showed marked cardiomegaly and ECG revealed
      atrial fibrillation and complete right bundle branch block. Two-dimensional
      echocardiogram showed a flail anterior leaflet of the tricuspid valve and severe
      tricuspid regurgitation. In December 1989, he underwent tricuspid valve
      replacement with Carpentier-Edwards bioprosthesis. The chordae tendineae to the
      anterior leaflet of the tricuspid valve were ruptured. Furthermore, an artificial
      cardiac pacemaker was implanted because of slow atrial fibrillation. His
      postoperative course was uneventful.

PMID- 7564023
TI  - [Syphilitic thoracic aortic aneurysm with destruction of vertebral body,
      producing numbness of lower extremities and paraplegia].
AB  - Numbness and paraplegia are uncommon complaints in patient with thoracic aortic
      aneurysm (TAA). The patient was a 64-year-old man. He suffered numbness and gait
      disturbance (paraplegia). The blood examination showed no positive findings
      except a Wassermann was positive. Roentgen examination of the chest showed two
      abnormal shadows like tumors. The CT and MRI revealed destruction of the
      vertebral bodies and TAAs adjacent to the spinal cord. After the graft
      replacement was performed, numbness and paraplegia disappeared. This suggests
      that in our patient the TAAs destruct the vertebral body and produce pressure on
      the spinal cord, causing numbness and paraplegia. We experienced a rare case of
      the syphilitic TAA producing bone destruction, numbness and paraplegia.

PMID- 7564024
TI  - [A surgical treatment of ruptured aortic dissection with non-opacified false
      lumen].
AB  - A 63-year-old woman was admitted to our intensive care unit suffering from severe
      chest pain and shock. Emergency CT scan demonstrated an acute type A aortic
      dissection with non-opacified false lumen and cardiac tamponade. The aortography
      showed ulcer like projection at the ascending aorta. An emergency operation was
      performed to replace the ascending aorta with a woven double-velour Dacron graft
      of 30 mm in diameter. It seems that an acute type A aortic dissection with non
      opacified false lumen has good prognosis. The presence of other complications,
      however, suggests that surgical treatment should be decided upon at an early
      stage.

PMID- 7564025
TI  - [A case report of left atrial free-floating ball thrombus in a patient without
      mitral valve disease].
AB  - A 77-year-old man who had a left atrial free-floating ball thrombus without
      mitral valve disease was operated. His electrocardiogram showed atrial
      fibrillation. Transesophageal echocardiography showed free-floating mass in
      dilated left atrium and intact mitral valve. Transesophageal echocardiogram was
      also useful for intra-operative management. At the operation, the mass proved to
      be a free-floating ball thrombus in the left atrium and the intact mitral valve
      was confirmed. The thrombus was removed, but we could not wean the patient from
      extra-corporeal circulation due to intra-operative myocardial infarction. Autopsy
      showed left ventricular hypertrophy and the focus of acute myocardial infarction
      in lateral wall and posterior wall of left ventricle. Furthermore, large
      organized thrombi were found in aorta and right main pulmonary artery. It was
      suggested that the patient had abnormal coagulative system or fibrolytic system
      preoperatively.

PMID- 7564026
TI  - [Surgical treatment for total anomalous pulmonary venous connection of Darling
      type Ib and IIb, using SVC-appendage anastomosis and pedicled right atrial flap].
AB  - A eight-day-old girl with total anomalous pulmonary venous connection of type I b
      + IIb underwent a total correction. Right atrium (RA) was entered through a
      vertical incision. Atrial septal defect (ASD) in the caudal aspect of fossa
      ovalis was enlarged by cutting the primum tissue. RA flap was sutured to ASD and
      intracardiac orifice margin of SVC to create a roof of pulmonary venous channel.
      SVC just cranial to entrance of common pulmonary vein was oversewn. Anastomosis
      between the cephalad SVC and opened right atrial appendage was made.
      Postoperative angiography showed wide PV channel and SVC channel.

PMID- 7564027
TI  - [Operative removal of esophageal leiomyosarcoma: a case report].
AB  - This is a case report of 56-year-old man complaining of dysphasia. Upon
      admission, his chest X-ray film revealed medium amount of fluid accumulation in
      the right pleural space. Cytological examination of the aspirated fluid revealed
      nothing particular. Preoperative radiological examination including esophagogram,
      CT and MRI demonstrated cystic appearance of mass lesion, measuring approximately
      5 cm in size located in posterior aspect of the lower portion of the mediastinum.
      Upon operation, it was found that a tumor with pedunculated connection to the
      esophageal muscle layer, suspecting diagnosis of leiomyoma of the esophagus.
      Then, tumor was removed together with the part of esophageal muscle.
      Postoperative pathology reported leiomyosarcoma of the esophagus with low grade
      malignancy. We added no esophagectomy. He made uneventful recovery without no
      sign of recurrence of the malignancy, 4 years after the surgery.

PMID- 7564028
TI  - [Empyema caused by perforation of metastatic colon cancer: a case report].
AB  - The patient was a 51-year-old female, underwent total gastrectomy for gastric
      cancer 6 years ago. She was admitted to a local hospital with the complaint of
      fever, the chest X-ray showed niveau in the left pleural cavity. Fecal material
      flowed out by drainage. Barium enema showed fistula of diaphragma from transverse
      colon. She was transferred to our hospital. Partial transverse colon resection
      and removal of the diaphragma fistula were performed. The colon tumor was
      histologically determined to be metastasis from gastric cancer with thoracic
      empyema.

PMID- 7564029
TI  - [A case of primary pulmonary hemangiopericytoma recurred locally 10 years after
      the first surgery].
AB  - Hemangiopericytoma is a rare tumor of vascular origin. This tumor has a malignant
      potential and often recurs or metastasize. A case of primary pulmonary
      hemangiopericytoma which recurred locally 10 years after the first surgery is
      presented. The histological appearance of the tumor had some findings of
      malignant potential in both of the primary and recurrent lesions. We discussed on
      malignant potential of this tumor in the number of mitotic figures, cellular
      atipia, and DNA ploidy pattern.

PMID- 7564030
TI  - [A case of bilateral thoracoscopic partial resection for unilateral spontaneous
      pneumothorax].
AB  - There is a high incidence of pneumothorax on the contralateral side in patients
      with unilateral spontaneous pneumothorax. This is because bullae and blebs of the
      lungs, the cause of this condition, are frequently present bilaterally. Recently,
      thoracoscopic partial lung resection has become more common and has been proven
      to have advantages such as less bleeding, less pain and a smaller skin incision.
      In view of the common occurrence of contralateral pneumothorax, bilateral
      simultaneous thoracoscopic partial lung resection for unilateral spontaneous
      pneumothorax is recommended for patients in their teens and twenties who have
      contralateral bullae and blebs.

PMID- 7564031
TI  - [Separate perfusion of upper and lower body under mild hypothermia during
      operation on the thoracoabdominal aorta].
AB  - During last 7 years, we performed 24 operations on the thoracoabdominal aorta.
      There were 9 true and 15 dissecting aneurysms. There were two cases of ruptured
      aneurysm and thoracoabdominal replacement was performed as a last stage operation
      for total aortic replacement in 4 cases. Three cases with aortic dissection died
      within 30 days after surgery. Femoro-femoral bypass was used in 4 cases (1 case
      died of brain damage, paraplegia and MOF), left heart bypass in 5 cases and
      separate perfusion of upper and lower body (SPULB) under deep hypothermia in 7
      cases (2 cases died of LOS and cerebrovascular accident occurred at 2 weeks after
      operation) and SPULB with mild hypothermia in 8 cases for circulatory support.
      There was one case of renal dysfunction and transient mild liver dysfunction
      occurred in 7 cases. There was no evidence on relationship between surgical
      outcome and methods of circulatory supports, but we recently prefer SPULB under
      mild hypothermia for thoracoabdominal surgery since intraoperative massive
      bleeding and cardiac arrest can be easily treated and major organs can be
      protected by introducing hypothermia in this perfusion technique.

PMID- 7564032
TI  - [Five cases of ASD-PDA complex: a review of 38 cases reported in Japan].
AB  - Five cases of ASD-PDA complex were experienced. The incidence of ASD-PDA complex
      was 1.2% of CHD in our institution. The age at operation was ranged from 10 days
      after birth to 2 years of age. Four patient were male and 1 was female. Also, 4
      patients had noncardiac anomalies, including Down syndrome, microcephaly, cleft
      palate, micrognathia, and cranioschisis. All patient had moderate or severe
      pulmonary hypertension. Three patients received ASD and DA closure under
      cardiopulmonary bypass, however, 2 patients were succeeded in decreasing CTR and
      pulmonary vascular shadow by ligation of DA. Operative and hospital mortality was
      none. We also studied concerning clinical features and surgical treatment by the
      review of 38 cases reported in Japan and our 5 cases.

PMID- 7564033
TI  - [Surgical treatment of metastatic lung tumor from colorectal cancer].
AB  - We have experienced thirty-one operations of metastatic lung tumors from
      colorectal cancer. Various factors affecting prognosis are studied based on 5
      year survival in this report. Overall 5-year survival rate was 32%. Statistical
      significance was present in the relationship between the prognosis and both
      maximum diameter of lesions and the disease free intervals (DFI) after surgery
      for metastatic lesions. Though not significant, sex, stage of primary lesion,
      nodal involvement, surgical procedure, postoperative serum CEA were likely
      affecting factors on the prognosis. In contrast, there were no relationship
      between the prognosis and following factors: age, location of the metastatic
      lesion, DFI after the operation for primary lesion and chemotherapy. Although
      pulmonary metastasis is essentially an index of the advanced state of malignant
      diseases leading to poor prognosis, long-term survivors were encountered in our
      series of surgical treatments for pulmonary metastases from colorectal cancers.
      It was concluded to be important to make efforts to extend the indication for
      surgical treatment, since the appropriate selection of patients revealed to give
      excellent results from our experience of colorectal cancer. In order to improve
      the prognosis, early detection of pulmonary metastases is quite important, since
      the incidence of nodal involvement proved to be higher in lesions with larger
      diameter resulting in inferior survivals from the present study. In addition, low
      incidence of nodal involvement in small-sized lesion may support possible
      applicability of thoracoscopic surgery in the excision of metastatic tumors
      locating at peripheral lesion.

PMID- 7564035
TI  - [New configuration of right ventricular dynamic cardiomyoplasty by latissimus
      dorsi for hypoplastic right ventricle].
AB  - The purpose of this experimental study is to evaluate the efficacy of linear-type
      right ventricular (RV) dynamic cardiomyoplasty in a setting of patch enlargement
      model for hypoplastic RV. In 6 puppies (6-8 kg), under a cardiopulmonary bypass
      (CPB), RV free wall and septal traveculation were resected and replaced with
      large pericardial patch, simulating RV patch enlargement of hypoplastic RV. A
      pedicled left LD, anchored to 3rd rib, wrapped onto the RV patch in parallel to
      RV long axis, while LD fixed to only RV diaphragma surface without wrapping LV
      surface. After the termination of CPB, LD flap was synchronously paced at 1:1
      ratio with cardiac beat with a trained-pulse stimuli (10-25 Hz). RV performance
      was tested by RV function curve (RVSWI vs CVP) and RV pressure-volume
      relationship (ESPVR) assessed by conductance catheter. RESULTS: LD graft
      stimuration showed significant augmentation of PAP (145 +/- 21%), PA flow (152 +/
      21%) and AP (128 +/- 23%) at CVP of 10 mmHg. RV function curve and ESPVR
      confirmed dramatical augmentation of RV performance by graft stimulation, which
      was identical to preoperative normal RV function even at the low CVP range.
      CONCLUSIONS: Linear LD myoplasty after patch enlargement of RV may viable
      surgical option for hypoplastic RV.

PMID- 7564034
TI  - [Repeat open heart surgery in a case associated with persistent left superior
      vena cava: a method of simple occlusion of L-SVC using an alternative extra
      pericardial approach and retrograde cardioplegia].
AB  - Twelve years ago, we reported a method of extrapericardial approach to the L-SVC.
      Since then we have used this approach and performed simple occlusion of L-SVC
      during cardiopulmonary bypass without any cerebral complications. We have been
      expecting for a long time and have believed that this method will be very
      valuable especially in repeat open heart surgery. A case of 49-year-old man
      successfully underwent a redo operation for mitral and tricuspid valve
      replacement using extrapericardial occlusion of the L-SVC and retrograde
      cardioplegia. Although there was a pitfall for retrograde cardioplegia in the
      persistent L-SVC and a possibility of steal of cardioplegic fluid through a
      branch of the accessory hemiazygos vein during retrograde cardioplegia for a case
      with persistent L-SVC, sufficient cardiac protection was obtained in the case
      presented.

PMID- 7564036
TI  - [Significance of combined use of anticoagulants and antiplatelet agents in the
      early stage after prosthetic valve replacement].
AB  - Patients who had undergone prosthetic valve replacement were treated with
      warfarin (anticoagulant) alone or in combination of ticlopidine (200 mg/day) or
      aspirin (81 mg/day) (anti-platelet agents). The study of blood coagulation
      factors and platelet aggregation were carried out with these cases. 1) The
      patients (n = 24) receiving warfarin for 21 days after prosthetic valve
      replacement revealed marked increases in PIVKA-II and vitamin K1-epoxide. The
      protein C activity was significantly lower than that before the operation. High
      levels of more than 5 ng/ml of TAT were found before operation and after warfarin
      administration for 21 days. 2) Warfarin did not affect platelet aggregation,
      whereas ticlopidine inhibited ADP-induced platelet aggregation and aspirin
      inhibited both collagen-induced and arachidonic acid-induced aggregation. In
      conclusion, combined use of anticoagulants and antiplatelet agents after
      prosthetic valve replacement will suppress not only the blood coagulation but
      also the platelet aggregation systems.

PMID- 7564037
TI  - [Epidural injection for postoperative pain relief after thoracoscopic surgery].
AB  - For the pain relief after thoracoscopic surgery, the epidural injection of
      buprenorphine was performed in 46 cases. In 28 cases, intermittent injection was
      performed before awaking from anesthesia. The effect was excellent in 6 cases,
      who were free from pain without any more injection after returning to the ward,
      and good in 27 cases, who sometimes felt dull pain and had another analgetics
      (intermittent epidural injection in 16 cases, intermittent epidural injection and
      another medication in 5 cases). In 18 cases, continuous injection was performed.
      The effect was excellent in 9 cases and good in 9 cases. It was concluded that
      the epidural injection had effective analgesic effect after thoracoscopic
      surgery, both in intermittent injection group and continuous injection group. For
      limited medication, the intermittent epidural injection was considered the first
      choice after thoracoscopic surgery.

PMID- 7564038
TI  - [A case of pentalogy of Cantrell with tetralogy of Fallot and left ventricular
      diverticulum].
AB  - We report a successful repair of tetralogy of Fallot and left ventricular
      diverticulum associated with pentaology of Cantrell. The repair consisted of
      partial infundibular septectomy, closure of ventricular septum, reconstruction of
      right ventricular outlet using monocuspid transjunctional patch, and resection of
      left ventricular diverticulum. The infundibulum was extremely elongated, caused
      by ventricular dextroversion, and the hypoplasia of pulmonary trunk was absent.
      Therefore, transjunctional patch was longer, even after infundibular septectomy.
      This report discuss the pathogenesis of these cardiac anomalies and surgical
      imlication.

PMID- 7564039
TI  - [Surgical treatment of coronary artery fistulas].
AB  - Coronary artery fistula is one of the most common coronary malformations and is
      being diagnosed with increasing frequency with widespread use of selective
      coronary arteriography. Twenty-one patients with coronary artery fistulas
      underwent surgical treatment at our institute between 1973 and 1994. The left
      coronary artery was most commonly involved, and the fistula communicated
      primarily with the pulmonary artery. Associated cardiovascular disease include:
      mitral stenosis (1), mitral insufficiency (1), partial anomalous pulmonary venous
      return (1), ventricular tachycardia (1), atrial septal defect (1), aortitis
      syndrome (1), and coronary arteriosclerotic narrowing (1). In five patients, the
      coronary artery fistulas were selectively ligated without CPB. In sixteen
      patients, in addition to selective ligation, the fistula ostia were closed from
      inside using CPB. There were no operative or late deaths in the patients who
      underwent operations. Thus, the risks of surgical correction appear to be
      considerably less than the potential development of serious and possibly fatal
      complications, even in asymptomatic patients.

PMID- 7564040
TI  - [Surgical treatment of congenital aortic stenosis by aortoseptal approach].
AB  - Between 1975 and 1994, six patients under 15 years old with congenital aortic
      stenosis underwent relief of left ventricular outflow tract obstruction (LVOTO)
      by aortoseptal approach. Although we got satisfactory relief of LVOTO in all
      patients, there were two late deaths. In one patient with residual ventricular
      septal defect (VSD), intractable ventricular arrhythmia developed 12 years
      postoperatively. Although the residual VSD closure was performed, the patient
      died of the arrhythmia. The another one who was the youngest 4-year-old boy
      suddenly died 4 months postoperatively. The detail about his death was unknown,
      but we presumed ischemic heart attack as the cause of his death. In 3 of
      remaining survived 4 patients, we encountered a few complications. They were
      right ventricular outflow obstruction, coronary artery injury and conduction
      system injury. All complications and problems we encountered in this series were
      related to the incision and the reconstruction of aortoseptal approach. In
      conclusion, the aortoseptal approach is effective technique for relief of LVOTO,
      but on the other hand it is invasive and not so safe operation. So we should be
      cautious about these complications and problems.

PMID- 7564041
TI  - [A successful case of emergency CABG using PCPS due to acute myocardial
      infarction].
AB  - A successful case of emergency CABG (Coronary Artery bypass Grafting) by using
      PCPS (Percutaneous Cardio Pulmonary Bypass) for a 60-year-old with shock due to
      acute myocardial infarction was reported. He developed shock due to acute
      myocardial infarction before arrival at our hospital. He was resuscitated by
      PCPS. Coronary angiography revealed that LMT was 99% stenosed and LAD just
      proximal was totally occluded. Emergency CABG was performed to LAD and CX using
      saphenous vein grafts. Post-operative course was uneventful and the patient was
      discharged at hospital two months after the operation. PCPS is useful for bridge
      until emergency CABG.

PMID- 7564042
TI  - [A successfully treated case of thoracoabdominal aortic aneurysm complicated with
      the coagulation disorder].
AB  - We could performed the safe operation for thoracoabdominal aortic aneurysm
      complicated with pre-DIC. A diagnosis of pre-DIC was made by laboratory data. Low
      heparin pretreatment was performed for the short term because we presumed the
      cause for pre-DIC was thromboses in aneurysm. That treatment was effective for
      the temporal remission of pre-DIC. In addition, during partial ECC low heparin (1
      mg/kg) and nafamostat mesilate (2 mg/kg/h) were used. As a result, during and
      after the operation blood loss was a little. In summary heparin pretreatment is
      useful therapy for DIC and pre-DIC in aortic aneurysm patients.

PMID- 7564043
TI  - [A successful case of ischemic cardiomyopathy associated with left ventricular
      aneurysm and mitral regurgitation].
AB  - A 67-year-old female patient underwent a left ventricular aneurysmectomy and
      mitral valve replacement for ischemic cardiomyopathy. The replacement was done
      through left ventricle rather than left atrium. She had heart failure of NYHA
      class IV despite aggressive medical therapy. Preoperative examination revealed a
      left ventricular aneurysm and mitral regurgitation of grade II with markedly
      reduced ventricular function (LVEF 17%). Mitral valve replacement through left
      ventricle preserving chorda of the mitral valve is a promising method to
      eliminate regurgitation and shorten the cardiac ischemic time.

PMID- 7564044
TI  - [A case report of an operation for graft stenosis with complete obstruction of
      the coronary artery].
AB  - A case report of an operation after CABG and AVR was presented. The patient was a
      52-year-old female. She underwent CABG with saphenous veins at 43 years old and
      AVR at 45 years old. She was admitted to our hospital due to acute myocardial
      infarction. Coronary angiography revealed that all the native coronary arteries
      were occluded at the proximal side, two grafts to RCA and CX were occluded, and
      LAD graft had a 99% stenosis. She became critically ill due to low cardiac output
      and acute renal failure. Endoartrectomy of the LAD graft was performed under CPB.
      Early postoperative course was uneventful. Severe ST depression in the pre
      operative ECG normalized in the postoperative ECG. But she had a chest pain again
      in the 4th postoperative week. She became critically ill and died on the 43rd
      postoperative day. It was thought that redo CABG should have been performed after
      her condition improved.

PMID- 7564045
TI  - [Aortitis syndrome with left coronary ostial occlusion and aortic regurgitation:
      a case report].
AB  - A 22-year-old woman with left coronary ostial occlusion and aortic regurgitation
      due to aortitis syndrome was reported. The coronary artery bypass grafting, using
      saphenous vein and aortic valve replacement were performed. The distal
      anastomosis of saphenous vein was performed to left anterior descending artery
      (Seg. 6), just distal to the origin of circumflex artery. The postoperative
      course was uneventful. There was no peri-prosthetic valvular leakage and bypass
      graft was patent.

PMID- 7564046
TI  - [A successful repair of the aortic dissection (DeBakey type I) with ischemic
      complications of the kidney and lower extremities].
AB  - A 65-year-old male was referred to our institution under diagnosis of aortic
      dissection which passed 1 month after the onset. An aortography revealed DeBakey
      type I aortic dissection with the left renal artery involvement and the very
      narrow true lumen of the abdominal aorta compressed by the pseudolumen,
      especially at the orifice of the right renal artery. On the 3rd day of admission,
      the patient manifested SVC syndrome, oliglia and pulselessness of the femoral
      artery bilaterally, that indicated ischemia of the kidney and the lower
      extremities. An emergency operation was performed, and the ascending aorta was
      replaced using open distal anastomotic technique for the distal site of the aorta
      under deep hypothermia and retrograde cerebral perfusion method. The ischemic
      symptoms and SVC syndrome were disappeared promptly after operation.
      Postoperative CTscan showed the narrow true lumen of the abdominal aorta expanded
      remarkably. The postoperative course was uneventful and the patient discharged on
      the 54th postoperative day.

PMID- 7564047
TI  - [Left diaphragmatic hernia due to blunt chest trauma complicated with
      intrapleural gastric perforation].
AB  - A 17-year-old male was injured by traffic accidents. Multiple left rib fractures,
      radiopacity of left hemithorax and rightward mediastinal shift lead us to the
      diagnosis of traumatic hemothorax. But left tube thoracostomy could not obtain
      any fluid. After this finding we suspected diaphragmatic hernia. Neither inserted
      nasogastric tube nor abdominal echogram could not lead to definitive diagnosis.
      Chest CT could identify stomach and spleen in the thoracic cavity. Insufflation
      of 300 ml air through nasogastric tube could not expand the stomach. By insertion
      of another thoracic tube some coffee-ground like materials could be obtained.
      Laparotomy disclosed rupture of left hemidiaphragm and intrathoracic displacement
      of the stomach and spleen. After reposition of stomach, we discovered 5 cm
      fissure of the stomach and left thoracic cavity filled with leaked gastric
      contents. Though reports of combined diaphragmatic hernia and gastric rupture are
      rare, these combination could occur if a patient with diaphragmatic hernia
      encounters blunt chest trauma on a full stomach.

PMID- 7564048
TI  - [A recurrence of benign fibrous mesothelioma of the pleura: a case report].
AB  - A 64-year-old man who complained of the right chest pain was admitted in our
      hospital. A mass shadow which revealed the extrapleural sign was shown in the
      chest X-ray. This patient was performed thoracotomy and a tumor invading to the
      intercostal muscles was resected. Pathological diagnosis was benign fibrous
      mesothelioma. About 10 months after this operation, we suspected the local
      recurrence of the tumor on the chest X-ray. The re-operation was performed, and
      we resected the recurrent tumor and the 2nd and 3rd ribs. Pathologically the
      resected tumor was benign fibrous mesothelioma.

PMID- 7564049
TI  - [Congenital cystic adenomatoid malformation of the lung: a case report in a
      newborn infant with severe respiratory failure and a review of the literature].
AB  - The patient was newborn infant with severe respiratory failure. The left upper
      lobe of her lung was occupied by multiple small cysts and it was getting worse in
      her condition soon after birth. So left upper lobectomy was underwent urgently
      four days later. Then she was recovering her strength. Pathological examination
      of resected specimen revealed congenital cystic adenomatoid malformation (CCAM)
      of the lung (type II lesion of Stocker's classification). It is reported that
      about seventy percent of CCAM present between birth and one month of age. Its
      prognosis is poor without operation. The lesion is showed by Chest-abdominal X
      ray and ultrasonography, and recognized to best advantage by computed tomography.
      Neonatal CCAM must be rapidly diagnosed and decided its indication of lobectomy,
      then its prognosis may be improved.

PMID- 7564050
TI  - [Studies on production of interleukin-1 beta (IL-1 beta) and granulocyte.
      Macrophage-colony stimulating factor (GM-CSF) by peripheral blood monocytes from
      patients with Mycobacterium avium-intracellulare complex (MAC) infection].
AB  - Production of Interleukin-1 beta (IL-1 beta) and granulocyte macrophage-colony
      stimulating factor (GM-CSF) by peripheral blood monocytes (PBMs) from patients
      with Mycobacterium avium-intracellulare complex (MAC) infection was assessed and
      the relationship with their clinical course was analyzed. PBMs were obtained from
      MAC-infected patients in their active stage as well as in the inactive stage and
      the healthy controls. Spontaneous release of IL-1 beta by PBMs from patients in
      the active stage was higher than those by the cells in the inactive stage or the
      healthy controls. On the other hand, spontaneous GM-CSF release by PBMs from
      patients in the active stage was higher than the healthy controls. When PBMs were
      stimulated with MAC-derived purified protein derivatives (PPD-B), increased
      production of both IL-1 beta and GM-CSF were obtained for PBMs in their active
      stage. While these enhanced production upon stimulation with PPD-B related to the
      persistent infection with MAC, the increased IL-1 beta production correlated with
      the exhausted nutritional state. Both IL-1 beta and GM-CSF produced by PBMs
      seemed to be closely related with the clinical course of human MAC infection.

PMID- 7564051
TI  - [Massive and progressive hepatosplenomegaly caused by disseminated nontuberculous
      mycobacteriosis in a patient with acquired immunodeficiency syndrome].
AB  - A 28-year-old hemophilia A patient was admitted to our hospital in July, 1991
      because of high fever, chronic diarrhea and anemia. The patient had been
      recognized as a asymptomatic carrier of human immunodeficiency virus (HIV) in
      1985 and had developed Pneumocystis carinii pneumonia and had been diagnosed as
      acquired immunodeficiency syndrome (AIDS) in 1990. Hematologic laboratory
      examinations on admission revealed pancytopenia and a CD4+ cell count of 3/mm3. X
      ray findings of chest and abdomen were normal and bacterial cultures of sputum,
      urine, blood, stool, cerebrospinal fluid and bone marrow yielded no pathogenic
      microorganisms. Microscopical examination of the stained specimens showed no acid
      fast bacilli. On his fifth hospital day, his liver and spleen enlarged markedly
      and an abdominal CT scan obtained on the 13th day revealed high-grade
      hepatosplenomegaly. Administration of several kinds of antibiotics, antifungal
      agents, antiviral agents, antituberculous agents and gamma-globulin medicines did
      not relieve the symptoms. On the 28th day the patient had developed a
      subarachnoid hemorrhage and died five days later. Retrospectively all cultures
      for acid-fast bacilli of the specimens on his admission yielded nontuberculous
      mycobacteria. The bacteria were identified as Mycobacterium avium by polymerase
      chain reaction and his disease was eventually diagnosed as disseminated
      Mycobacterium avium complex (MAC) infection. The liver and spleen weighed 2,660 g
      and 1,840 g respectively at autopsy. Although hepatosplenomegaly is commonly
      recognized in AIDS patients with disseminated MAC infection, such massive and
      rapid enlargement has been rarely observed. This case study emphasize the
      importance of diagnosis and rapid treatment at the early stage of MAC infection.

PMID- 7564053
TI  - [A case of solitary tuberculosis in lower lung field showing marked pleural
      indentation complicated with chronic renal failure with special reference to
      mechanism of of formation of pleural retraction].
AB  - A case of 62-year-old male patient with tuberculosis in the lower lung field of
      right side was reported. The case showed a solitary lesion in S8b of 2.5 x 2.0 cm
      in size and was detected by the mass survey. The case was complicated with
      chronic renal failure and was treated by lobectomy because of suspicion of lung
      cancer, as there was a marked pleural indentation on CT. By examining the
      resected specimen, the following findings were revealed. The solitary exudative
      tuberculous lesion located in the margin of the basal segment extended both to
      the costal and diaphragmatic pleura, and a small triangular shaped normal lung
      parenchyma located at the periphery of the lesion was isolated, and the air flow
      from the lower lobar bronchus was cut. As a result, hyperinflation of the
      isolated normal lung took place through collateral air leak and check-valve
      mechanism (The Culiner Theory), finally the pleural constriction was formed at
      the boundary between the lesion where the elasticity was lost and the
      hyperinflated parenchyma.

PMID- 7564052
TI  - [A case report of the atypical tuberculosis associated with AIDS].
AB  - A 49-year-old Japanese male who had been imprisoned for five years then lived
      with other men complained of fever, constitutional symptoms and a 12 kg weight
      loss over four-month period. He was referred to us as his gastric washings were
      positive for acid-fast bacilli (AFB). Chest X-ray showed patchy, infiltrative
      small shadows primarily in the right upper lung field without hilar adenopathy.
      Before transfer to our hospital, tuberculosis chemotherapy composed of SM, INH,
      RFP and PZA was initiated. Over the next three weeks, fever dropped, and the
      above described abnormal shadows on the chest X-ray improved, leaving small
      cystic lesions. Although a sputum smear was negative for AFB, M. tuberculosis was
      isolated from cultured samples and sensitive to all standard anti-tuberculous
      drugs. AFB were also demonstrated on a touch imprint of biopsied cervical lymph
      nodes. Sputum samples turned negative one month later both on smear and culture.
      Moreover, high fever developed and another abnormal shadow indicative of
      Pneumocystis carinii (PCP) appeared in the left lung field one month after the
      admission. White plaque was noted in the oral cavity. Dark red nodules were
      observed on the upper extremities and chest wall, and diagnosed histologically as
      Kaposi's sarcoma. Serologic testing for HIV was positive both by PA and Western
      blot methods, thus AIDS was diagnosed according to the CDC surveillance case
      definition for AIDS with the diagnosis of tuberculosis. The patient died of
      wasting syndrome on the 90th hospital day. On autopsy, small thin-walled cavities
      were observed in the right upper lung, correlating with earlier X-ray and CT
      findings.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564054
TI  - [Status quo of pyrazinamide as an antituberculosis drug].
AB  - Pyrazinamide (PZA), an antituberculosis agent, was first synthesized in 1940 by
      Hall and Spoerri and a clinical trial was carried out since 1949 by Yeager and
      others. Its usefulness as a potent antituberculosis drug was first reported by
      them in 1952. PZA was once believed to be a secondary choice drug for cases with
      refractory tuberculosis and/or relapsed cases which are resistant to all other
      antituberculosis drugs. There was some hesitation among doctors to use PZA for
      the initial treatment of tuberculosis because of rather high incidence of liver
      impairment after the use of regimens with PZA. It was, however, revealed later
      that this was not always true as PZA was ordinarily employed for clinical use in
      combination with ethionamide and/or cycloserin, and the latter drugs are both
      known to be hepatotoxic, too. PZA has a unique biological activity observed in
      murine experimental tuberculosis. The study showed that PZA when administered to
      animals, enters into the bacilli-ingested macrophages and exerts its killing
      effect on the bacilli under the environment of acidic pH inside the phagosome of
      the cells and in areas of acute inflammation both of which favors the acid-fast
      bacilli to stay in a dormant state and proliferate very slowly. This unique
      killing ability of PZA which is deficient in other drugs has recently spotlighted
      PZA once again as a pivotal and first line agent for the 6 months short course
      chemotherapy of tuberculosis. Sterile eradication of microbe is indispensable for
      the chemotherapy of tuberculosis, and the potency of a certain antituberculosis
      agent could be assessed by the availability of negative conversion of bacilli in
      sputum by culture within two months of administration of the drug. Another
      important aspect to assess the potency of a drug is to observe the relapse rate
      after the termination of therapy with the drug. The addition of PZA to the
      ordinary regimen consisting of INH, RFP and SM/EB has been reported to raise the
      negative conversion rate of bacilli from 60-70% by the regimen without PZA to as
      high as 80-90% by the regimen with PZA. In addition, there is no difference in
      the relapse rate of about 0-2% within 2 years after the termination of
      chemotherapy between the two regimens; 6 months with PZA and 9 months without
      PZA. Thus, the addition of PZA to the ordinary regimen enabled us to shorten the
      duration of antituberculosis chemotherapy than before.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7564055
TI  - [Surveillance of tuberculosis in Japan].

PMID- 7564057
TI  - [Reproducibility of MTD system for detection of Mycobacterium tuberculosis: a
      cooperative study among six laboratories].
AB  - The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) is a rapid
      test for the detection of Mycobacterium tuberculosis, utilizing the rRNA
      amplification method. For assessing the reliability and reproducibility of the
      method, a co-operative blind study was conducted among 6 laboratories. Materials
      for test were sputum and water samples containing known numbers of Mycobacterium
      bovis BCG or Mycobacterium avium, and samples without bacteria. From three of 6
      laboratories, false-positive results were reported for bacteria negative samples,
      however, the ratio was below 10%; 8.3% (3/36 samples), 5.6% (2/36), and 2.8%
      (1/36), respectively. It indicates the indispensability of negative controls for
      sample pretreatment and RNA extraction stages in the routine MTD test. In every
      laboratory, all the samples with 10(2) BCG in water and 10(4) BCG in sputum were
      found to be MTD positive. For the sputum samples with 10(2) BCG, positive results
      with the ratio above 80% were reported from 4 laboratories. These results
      indicate that the MTD test based on rRNA amplification method is quite useful for
      the rapid diagnosis of M. tuberculosis infection.

PMID- 7564056
TI  - [The evaluation of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF
      alpha) level in peripheral blood of patients with active pulmonary tuberculosis].
AB  - We investigated the serum level of IL-8 and TNF-alpha using ELISA in 16 patients
      with active pulmonary tuberculosis before administration of antituberculous drugs
      and in age-, smoking habit-matched 20 healthy controls. The mean level of serum
      IL-8 in patients with active pulmonary tuberculosis was significantly higher than
      that in healthy controls (P < 0.001). The mean level of serum TNF-alpha in
      tuberculosis patients was also high, while TNF-alpha was not detectable in the
      sera of healthy controls. We also examined the relationship between clinical
      pictures mainly defined by radiographic findings and the serum levels of IL-8 and
      TNF-alpha. The serum IL-8 level of 9 patients with tuberculous cavity is
      significantly higher than that of 7 patients without cavity. (P < 0.05) We
      classified the patients with cavities into two subgroups according to the
      radiographic classification of the Japanese Society of Tuberculosis. Four
      patients with advanced lesions on chest X-ray showed higher serum IL-8 level than
      5 patients with moderate lesions (P < 0.05). On the other hand, there was no
      correlation between serum TNF-alpha level and radiographic findings. These
      results suggest that IL-8 appears to be involved in the formation of tuberculous
      cavitary lesion.

PMID- 7564058
TI  - [A case of miliary tuberculosis during pregnancy in a patient on hemodialysis].
AB  - A 33-year-old woman had been on hemodialysis since she was 25 years old. In
      September, 1993, she had cough, which gradually increased in severity, and was
      accompanied by slight fever. No abnormality was observed on the chest radiography
      taken on November 2. However, bilateral diffuse miliary shadows were observed on
      the radiograph taken on November 30. Tubercle bacilli were detected by the
      examination of sputum smear. As she was pregnant 20 weeks, therapeutic abortion
      was done on December 8. A case of miliary tuberculosis occurring during pregnancy
      in a patient on hemodialysis has not been documented in Japan to date, and the
      first case in Japan was reported with a review of the literature.

PMID- 7564059
TI  - [A case of miliary tuberculosis with skull tuberculosis].
AB  - A 47-year old woman was admitted to our hospital with complaints of headache and
      right occipital swelling. Brain CT scan showed right occipital bone defect with a
      sequestrum and soft tissue swelling. T1 weighted MRI enhanced by GD-DTPA revealed
      several nodules. A right occipital craniotomy was performed. Subcutaneous pus and
      a well-circumscribed yellowish, firm mass which existed under the bone defect was
      extirpated. Pathologically, this mass was considered to be a tuberculoma and
      intracranial nodules were suspected to be cerebral tuberculosis. Anti-tuberculous
      therapy was started. Since her admission fecal occult blood continued and
      endoscopic examination with biopsy revealed sigmoid colon cancer. Sigmoidectomy
      was performed and she has been well during 1 year post-operative follow up.
      Although tuberculous disease are decreasing in number in our country, we must
      take into account of the existence of skull tuberculosis.

PMID- 7564060
TI  - [Epidemic of tuberculosis in Meiji and Taisho eras in Japan and excess deaths
      from tuberculosis in females].
AB  - Acute increase in tuberculosis mortality between 1885 and 1910 could be explained
      by rapidly increased birth rate, consequently large expansion of noninfected
      population, and gradual increase in opportunity of contact with infectious
      patients by changing working environments and living conditions. Prevalence of
      tuberculosis patients was not so few in the beginning of Meiji era. Vicious
      spiral of increased young susceptibles, many infectious sources and increased
      opportunity of infection had been continued for long. Lower nutrition from infant
      to adult, hard work and poor living conditions had worsen prognosis of the
      patients. Nation-wide tuberculosis control campaign, mainly avoiding contact with
      patients and contaminated materials had started around 1910 and then issued
      Factory act which had been improved working conditions in the factories, although
      the speed was very slow. Tuberculosis mortality began to decrease in 1910s, but
      sharp temporary rise of tuberculosis mortality was marked in 1918-19 by epidemic
      of influenza, then the mortality had been declined again. Excess mortality by
      influenza caused temporary reduction of infectious sources, which had affected
      mortality rate of tuberculosis in the younger ages after 1920. Large raise-up of
      wages for factory workers around 1920 and increase trend in income for other
      workers by economic growth since 1900 had been improved not only working and
      living conditions, but also dietary life with increased higher intake of animal
      foods. Female excess deaths from tuberculosis comparing those of males had
      continued until 1930, then male mortality exceeded females. Mobilization of young
      women to spinning and textile industries in Meiji and Taisho eras forced to
      increase in tuberculosis mortality among them.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564062
TI  - The future of nursing in home health.
AB  - The home health industry has been expanding faster than any other segment of
      health care. This growth is expected to increase and many exciting opportunities
      will be available for nurses. A model utilizing advanced practice nurses in home
      health care utilizing is discussed.

PMID- 7564061
TI  - Consumer trends in self diagnosis, home testing and over the counter medication:
      implications for the registered nurse.
AB  - Consumers are being called upon to assume more responsibility for their own
      health promotion and disease prevention practices. This challenge has motivated
      consumers to embrace the use of over the counter medications (OTC) and self
      testing devices with enthusiasm. Indeed, many chronic and short term ailments
      respond well to OTC's. Pharmaceutical companies, anxious to expand their profit
      margins, have bombarded consumers with intensive advertising. This information
      highway has made product names household words. The attendant dangers with OTC's
      are the same as for prescribed medications. Self testing devices are likewise
      subject to misinterpretation. This new patient independence has created
      additional challenges for registered nurses.

PMID- 7564063
TI  - Pregnancy and cocaine: a charge to nurses.

PMID- 7564064
TI  - School-based clinics: overcoming the obstacles.
AB  - Obstacles to the establishment of school-based clinics are investigated to
      determine possible strategies for the future. The current social environment
      necessitates a health care model that provides increased access and improved
      outcomes for children in particular. The advanced registered nurse practitioner
      is an integral part of the school-based clinic. Although opposition to school
      based clinics has been well organized in the past, proponents are learning new
      ways to deal with this challenge.

PMID- 7564065
TI  - Investigating forensic nursing.
AB  - Forensic nurses are making a positive impact in our society today. They are
      reaching out to aid victims of violence by not only attending to their injuries
      and emotional distress, but also by identifying, collecting, and preserving vital
      evidence that will be needed to assist their patients to seek justice through the
      legal system. Misinterpretation or failure to properly obtain evidence may result
      in a miscarriage of justice. Helping victims obtain validation of their injustice
      is crucial to their healing process and may be of critical importance in the
      effort to avoid further victimization. Forensic nurses work with victims of child
      abuse, elder abuse, domestic violence, sexual assault, and persons involved with
      violence or imminent death. This area includes psychiatric specialists who
      intervene not only with victims but also with perpetrators of violent and/or
      sexual acts.

PMID- 7564066
TI  - Evidence for a role of protein phosphatases 1 and 2A during early nephrogenesis.
AB  - Although most transcriptional events appear to be modulated by reversible protein
      phosphorylation, little is known about the role of this regulatory system during
      the development of mammalian organs. Here we have studied the serine/threonine
      protein phosphatases (PP) 1 and 2A in the early embryonic rat kidney with regard
      to expression and effects on growth and differentiation. All isoforms of PP-1 and
      PP-2A were ubiquitously expressed in 15-day embryonic (E15) kidneys (in situ
      hybridization studies). In contrast, mRNA for inhibitor-1 (I-1), an endogenous
      inhibitor of PP-1, was detected only in undifferentiated stem cells in the outer
      cortical area. I-1 is a novel marker for these cells. The abundance of the PP-1
      protein, confirmed with immunoblotting, was high in the embryonic kidney. In
      organ culture of E13 kidneys, okadaic acid (OA), an exogenous inhibitor of PP-1
      and PP-2A, dose-dependently inhibited growth and nephron formation (apparent half
      maximal effect at 6 nM). OA 10 nM had little effect on the growth of cultured E15
      kidneys, whereas nephron formation was disturbed and morphological evidence of
      apoptosis was seen. In summary, this study points towards important roles for
      protein phosphatases 1 and/or 2A in regulation of mitogenic activity in the early
      embryonic kidney.

PMID- 7564067
TI  - PDGF and TGF-beta mediate collagen production by mesangial cells exposed to
      advanced glycosylation end products.
AB  - Deposition of type III collagen protein is increased when cultured rat mesangial
      cells are cultured in media containing high glucose concentrations. Possible
      mechanisms for this effect include the production of growth factors, such as PDGF
      and TGF-beta, and the formation of abnormal glucose-protein adducts called
      advanced glycosylation end products (AGEs). In our studies, neutralizing
      antibodies to PDGF and TGF-beta prevented increased type III collagen deposition
      by mesangial cells exposed either to high glucose media or to low glucose media
      containing AGEs. Daily addition of PDGF or TGF-beta stimulated type III collagen
      production. However, while co-incubation with the TGF-beta Ab prevented PDGF
      stimulated type III collagen production, the PDGF Ab did not prevent TGF-beta
      stimulated type III collagen production. Daily addition of PDGF or TGF-beta
      stimulated, while AGEs inhibited, mesangial cell proliferation after 96 hours. We
      propose that high extracellular glucose and AGEs stimulate type III collagen
      production by pathways that involve the intermediate formation of PDGF and TGF
      beta by mesangial cells. PDGF may increase type III collagen production by
      stimulating the intermediate production of TGF-beta. Exposure to high glucose,
      AGEs, or TGF-beta also leads to impaired mesangial cell proliferation. The
      autocrine effects of TGF-beta and PDGF play important roles in the effects of
      high extracellular glucose and AGEs on cultured mesangial cells.

PMID- 7564068
TI  - Effects of Ca++ and glycine on lipid breakdown and death of ATP-depleted MDCK
      cells.
AB  - The relationships between cytosolic free calcium (Caf), cell associated glycine,
      phospholipid hydrolysis and cell death were investigated in Madin-Darby canine
      kidney (MDCK) cells injured by depletion of adenosine triphosphate (ATP). Glucose
      free incubation for three hours with a mitochondrial uncoupler resulted in
      progressive loss of glycine from cells. However, they were not lethally injured
      unless a perturbation of Ca++ homeostasis was also induced. Exposure to a Ca++
      ionophore and uncoupler in 1.25 mM Ca++ medium (+Ca) resulted in accelerated cell
      death. ATP depleted cells with ionophore in 100 nM Ca++ medium (-Ca) were also
      lethally injured, but after a significant delay. Depletion of glycine preceded
      death in both groups of cells. Exogenous glycine (5 mM) protected +Ca cells
      against lethal membrane damage, but the beneficial effects were lost over a
      period of time. In contrast, -Ca cells were completely protected throughout.
      Phospholipid mass and radioactive label in lipid fractions of cells prelabeled
      with 3H-oleic acid were measured. Accelerated death of +Ca cells was accompanied
      by large decreases of phospholipid mass, loss of phospholipid label, and
      accumulation of unesterified labeled fatty acid. These changes were greatly
      decreased by incubation in -Ca medium. On the other hand, protection by glycine
      could not be attributed to modifications of either the massive breakdown of
      phospholipids that occurred in +Ca cells, or the modest changes seen in -Ca
      cells. In +Ca cells, the deleterious effects of increased Caf and phospholipid
      breakdown ultimately prevailed over protection by the amino acid. Thus, separate
      pathways of cell death associated with increased Caf and decreased glycine were
      defined in ATP depleted, Ca(+)- permeabilized MDCK cells. Calcium excess and
      massive phospholipid loss are features of a damage process that occurs
      independently of whether cells are protected by glycine or not. Conversely, the
      glycine sensitive component of injury is expressed regardless of whether
      intracellular Ca++ is increased, or large phospholipid losses occur. ATP
      depletion in -Ca medium provides a system to study mechanisms of glycine
      cytoprotection uncomplicated by Ca++ toxicity.

PMID- 7564069
TI  - Association of calcium oxalate monohydrate crystals with MDCK cells.
AB  - Many factors are presently known which determine the risk of calcium oxalate
      (CaOx) stone formation in the kidney, although the early events in the
      pathogenesis of this disease are still to be elucidated. One of these early
      events is the interaction of intraluminal crystals with the epithelial cells
      lining the renal tubules. In this study we determined the interaction of
      approximately 2 microns calcium oxalate monohydrate (COM) crystal with monolayers
      of Madin-Darby canine kidney (MDCK) cells grown on porous supports in a two
      compartment culture system. Crystal-cell interaction studies were performed after
      the monolayers reached their highest level of gamma-glutamyltranspeptidase (gamma
      GT) enzyme activity, a marker for brush border development. Technical aspects
      were evaluated, such as the size and morphology of the crystals and the influence
      of incubation time, temperature and pH on crystal-cell interaction. Kinetic data
      demonstrated that an equilibrium between free and associated particles was
      reached within 30 minutes. Crystal-cell interaction was often associated with
      cell damage. However, evidence is provided that in an environment that was
      saturated with calcium oxalate, MDCK cells in an environment that was a certain
      amount of COM crystals without sustaining measurable injury. After initial
      attachment to the cell surface, crystals were taken up and subsequently
      eliminated again from the monolayers. The model system described in this paper
      provides a tool for detailed studies of processes that are involved in renal
      cellular handling of luminal COM crystals.

PMID- 7564070
TI  - Alpha-adrenoceptors and angiotensinogen gene expression in opossum kidney cells.
AB  - To investigate whether alpha (alpha)-adrenoceptor agonists have a stimulatory
      effect on the expression of the angiotensinogen (Ang) gene in opossum kidney (OK)
      cells, we used OK 27 cells with a fusion gene containing the 5'-flanking
      regulatory sequence of the rat angiotensinogen gene fused with a human growth
      hormone (hGH) gene as a reporter, pOGH (Ang N-1498/+18), permanently integrated
      into their genomes. The level of expression of the pOGH (Ang N-1498/+18) was
      quantitated by the amount of immunoreactive-human growth hormone (IR-hGH)
      secreted into the medium. The addition of iodoclonidine (alpha 2-adrenoceptor
      agonist, 10(-13) to 10(-9) M) and phorbol 12-myristate 13-acetate (PMA, 10(-13)
      to 10(-5) M) stimulated the expression of pOGH (Ang N-1498/+18) in a dose
      dependent manner, whereas the addition of phenylephrine (alpha 1-adrenoceptor
      agonist, 10(-13) to 10(-5) M) had no effect. The stimulatory effect of
      iodoclonidine was blocked by the presence of yohimbine (alpha 2-adrenoceptor
      antagonist) and staurosporine (an inhibitor of protein kinase C) but not blocked
      by the presence of prazosin (alpha 1-adrenoceptor antagonist) or Rp-cAMP (an
      inhibitor of cAMP-dependent protein kinase A). The addition of iodoclonidine,
      phenylephrine or PMA had no effect on the expression of pTKGH in OK 13 cells, an
      OK cell line, into which had been stably integrated a fusion gene, pTKGH
      containing the promoter/enhancer DNA sequence of the viral thymidine-kinase (TK)
      gene fused with a human growth hormone gene as a reporter.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7564071
TI  - Platelet-derived growth factor A-chain expression in developing and mature human
      kidneys and in Wilms' tumor.
AB  - Regulated expression of PDGF A-chain may be important in kidney development. We
      employed two polyclonal antisera to detect expression of PDGF A-chain in fetal
      and normal adult kidneys by immunohistochemistry. Specificity of the antisera was
      demonstrated by Western blots of fetal and adult kidneys, demonstrating
      monospecific bands at 10 to 15 kD, and by absorption studies with PDGF-A peptide.
      PDGF A-chain is uniformly expressed by visceral glomerular epithelial cells and
      the epithelial cells of the distal nephron, including collecting ducts and
      contiguous urothelium lining the renal pelvis, in both fetal and adult kidneys.
      Fetal kidneys also demonstrate expression of PDGF A-chain at the earliest stages
      of vesicle formation from the metanephric blastema; this expression is then only
      intermittently detectable in developing glomeruli until differentiation of
      visceral epithelial cells occurs. Fetal and mature arterial smooth muscle cells,
      and some express PDGF A-chain. In situ hybridization with a riboprobe made from
      PDGF A-chain cDNA showed close correlation of mRNA expression with protein
      immunohistochemistry. PDGF A-chain expression was also identified in epithelial
      elements of 5/6 Wilms' tumors studied. These are the first studies to localize
      PDGF A-chain expression in human kidney and suggest sites of activity for PDGF A
      chain in development, neoplasia, and in the renal arterial sclerosis of aging.

PMID- 7564072
TI  - Three-dimensional analysis of glomerular morphology in patients with subtotal
      nephrectomy.
AB  - Previous studies documented that single section examination of kidney tissue
      underestimates glomerulosclerosis and that three-dimensional examination of
      glomerular morphology improves recognition of the incidence and distribution of
      sclerotic changes within the glomerular capillary tuft. We have adopted this
      technique to evaluate the true frequency and the spatial extent of
      glomerulosclerosis in patients who were subjected to extensive renal mass
      reduction. We re-evaluated four kidney biopsies of patients with a solitary
      kidney who had undergone partial nephrectomy for renal-cell carcinoma.
      Histopathological examination aimed at detection of glomerular sclerotic lesions
      was performed on serial sections (from 75 to 93 serial sections for each biopsy,
      3 microns thick) together with three-dimensional morphometric analysis of
      glomerular tuft and sclerotic areas using a computer-based image processing
      system. Results were compared with observations based on more conventional single
      section evaluation of the same biopsies. Among 65 glomeruli examined by three
      dimensional morphometric analysis, only 8% were normal, 42% revealed segmental
      sclerosis and 51% global sclerosis. These results confirmed that single section
      evaluation grossly overestimates the number of normal glomeruli (37% vs. 8%,
      respectively), since the majority of glomeruli classified as normal are indeed
      affected by sclerotic changes in areas typically out of the section plane. The
      three-dimensional distribution of sclerosis is characterized by the appearance of
      multi-focal areas affecting a small capillary tuft volume (< 10%) which
      ultimately propagate to the entire capillary tuft. Despite the maintenance of
      renal function, at the time of biopsy in patients with extensive ablation of
      renal mass, the incidence of glomerulosclerosis affects almost the entire
      glomerular population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564074
TI  - Renovascular disease in older patients beginning renal replacement therapy.
AB  - Renovascular disease (RVD) in older patients can cause progressive renal
      insufficiency and even end-stage renal disease (ESRD). The frequency of this
      clinical problem is not well defined. Renal duplex sonography (RDS) correctly
      identifies the presence of RVD with an overall accuracy of approximately 95%.
      Therefore, the purpose of this study was to utilize RDS as a noninvasive tool to
      identify the presence of critical RVD (> or = 60% diameter-reducing stenosis or
      occlusion) in patients 50 years of age or older beginning renal replacement
      therapy. A total of 53 consecutive participating patients were prospectively
      interrogated. Complete interrogations occurred in 45 of the 53 patients (85%),
      and 92 of the 103 kidneys (89%). Critical RVD was noted in 10 of 45 patients
      (22%). RVD was bilateral in 5 patients, unilateral in 5 patients, and there were
      4 renal artery occlusions noted. All patients with critical RVD were white (10 of
      25 white patients or 40%). Total pack years of smoking as well as associated
      cardiovascular and cerebrovascular conditions were greater in those patients with
      critical RVD compared to those without. These results indicate that RDS remains
      technically feasible as renal blood flow and function decline. Unsuspected RVD
      possibly contributory to renal insufficiency exists in a significant number of
      primarily white patients 50 years of age or older beginning renal replacement
      therapy. These patients are generally smokers with a high frequency of associated
      extrarenal atherosclerosis The addition of RVD as a separate category of disease
      causing ESRD would improve U.S. Renal Data System ESRD classification. RVD should
      be recognized as a cause of ESRD.

PMID- 7564073
TI  - Glomerulopathy associated with predominant fibronectin deposits: a newly
      recognized hereditary disease.
AB  - A newly recognized type of familial glomerulopathy observed in patients of both
      sexes in six families is reported. Proteinuria, often within the nephrotic range,
      microscopic hematuria, hypertension and a slowly decreasing renal function over
      several years were common. No underlying systemic diseases were identified.
      Generally, light microscopy showed enlarged glomeruli with minimal
      hypercellularity and with extensive deposits in the mesangium and subendothelial
      space. By electron microscopy, granular deposits with some admixture of fibrils
      were most common. In one family, the deposits were predominantly fibrillary.
      Immunoglobulins and complement factors were inconstant or lacking. A main finding
      was a strong immune reactivity to fibronectin, corresponding to the distribution
      of the deposits. In one patient, the deposits recurred in a renal transplant.
      There was no indication of systemic deposition. Abnormalities in the metabolism
      of circulating fibronectin may play a pathogenetic role in this disease of
      probably autosomal dominant inheritance.

PMID- 7564076
TI  - Bony content of oxalate in patients with primary hyperoxaluria or oxalosis
      unrelated renal failure.
AB  - Oxalate retention occurs in end-stage renal failure. Regular dialysis treatment
      does not prevent progressive accumulation of oxalate in cases of ESRF due to
      primary hyperoxaluria (PH), whereas such accumulation seldom seems to occur in
      oxalosis-unrelated ESRF. To elucidate this issue we have measured the bony
      content of oxalate on biopsies of the iliac crest taken from 32 uremic patients,
      7 of them with ESRF associated with PH1 (6 cases) or PH2 (1 case). Ten subjects
      with normal renal function and no evidence of metabolic bone disease were taken
      as controls. Only trace amounts levels of oxalate were detected in normal
      subjects and oxalate to phosphate ratio was below 3:10,000. Non-PH dialyzed
      patients exhibited fivefold increases in oxalate levels, which rose to 5.1 +/-
      3.6 mumol/g bony tissue. Calcium oxalate was estimated to represent 0.18% of the
      hydroxyapatite content of bone. Oxalate amounts were neither related to pre
      dialysis plasma levels of oxalate, nor with duration of dialysis treatment,
      suggesting that accumulation was not progressive disorder. Oxalate levels were
      slightly higher in patients with a low turnover osteodystrophy compared to those
      with a high turnover pattern. Dialyzed patients with PH had remarkable increases
      in oxalate levels, which ranged between 14.8 and 907 mumol/g bony tissue. Oxalate
      deposition appeared to be progressive in that oxalate levels were significantly
      related to time on dialysis. In three patients calcium oxalate was a significant
      fraction of the mineralized bone. The occurrence of calcium oxalate crystals
      affected the histomorphometric patterns, that were featured by an increase in
      resorptive areas and a decrease in bone formation rate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7564075
TI  - Pyruvate neutralizes peritoneal dialysate cytotoxicity: maintained integrity and
      proliferation of cultured human mesothelial cells.
AB  - Toxic effects of commercially available peritoneal dialysate (PD) fluid include
      damage to mesothelial cells (MC), causing a severely disturbed proliferation of
      cultured MC. We investigated the injury to the cell membrane (by release of
      lactate dehydrogenase, LDH), the proliferation (by cell counts and by 3H
      thymidine incorporation), and optional the cytokine generation (by IL-1 receptor
      antagonist production, IL-1 ra) of cultured human MC during the 48 hours after a
      30 minute exposure to PD containing either 35 mmol/liter sodium lactate or sodium
      pyruvate. All solutions had a pH of 5.2 to 5.6 and were composed as standard PD.
      Glucose contents of 1.36 and 3.86 mmol/liter were tested. After exposure to the
      lactate-PD containing 1.36% glucose, LDH activity was increased by more than 30%,
      proliferation of MC was inhibited by more than 30%, and IL-1 ra production was
      reduced significantly when compared to pyruvate-PD and the control solution.
      After preincubation with 3.86% glucose containing PD, all negative effects became
      even more pronounced in the lactate group whereas the MC maintained their
      integrity, rate of proliferation and IL-1 ra release after pre-exposure to
      pyruvate containing PD. These results suggest that the acute toxic effects of
      commercially available PD on the integrity, proliferation and IL-1 ra production
      of MC can be avoided by the use of sodium pyruvate instead of sodium lactate.

PMID- 7564077
TI  - Lipid-lowering therapy in patients with renal disease.
AB  - A growing number of clinical trials have examined the effects of different lipid
      lowering strategies in patients with renal disease. We carried out a meta
      analysis to compare and contrast the relative efficacy of various antilipemic
      therapies in different renal disease settings. Studies that investigated one or
      more therapies designed to lower serum lipids were combined using weighted
      multiple linear regression. The analysis adjusted treatment effects for
      differences in baseline lipid levels and possible placebo effects. The results
      showed that antilipemic therapies generally had similar effects on lipids in
      different renal disease settings. In nephrotic syndrome the greatest and most
      consistent reductions in low density lipoprotein cholesterol (LDL) were seen with
      3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (regression
      coefficient with 95% confidence interval in mg/dl = -63, -79 to -46). Similar
      results were seen for LDL in renal transplant (-51, -57 to -45), renal
      insufficiency (-62, -82 to -42), hemodialysis (-65, -80 to -50) and continuous
      ambulatory peritoneal dialysis (CAPD) patients (-84, -104 to -64). Fibric acid
      analogues had less effect on LDL, but caused greater reductions in triglycerides:
      -132, -178 to -87, in nephrotic syndrome; -69, -93 to -45 in transplant: -107, 
      169 to -45 in renal insufficiency; -72, -120 to -24 in hemodialysis; and -96, 
      162 to -30 in CAPD. In general, the effects of diet and other therapies were less
      consistent. Despite possible limitations of this meta-analysis, the results
      provide a useful framework for choosing antilipemic therapy, and point to areas
      for future long-term studies examining the safety and efficacy of lipid lowering
      strategies in patients with renal disease.

PMID- 7564078
TI  - Detection of oxidants in uremic plasma by electron spin resonance spectroscopy.
AB  - Depletion of antioxidants and the presence of products of free radical damage in
      plasma suggest that oxidative stress is increased in uremia. We have developed an
      application of electron spin resonance spectroscopy, and used this method to show
      that a stable oxidizing component or components of plasma accumulate in uremia.
      No oxidizing activity was detectable in plasma from subjects with normal renal
      function. The oxidant was detected by its capacity to oxidize the spin trap 3,5
      dibromo-4-nitrosobenzene sulphonate (DBNBS). The oxidant was dialyzable from
      plasma, had an upper molecular weight limit of about 3,000 Daltons and was stable
      over many months. Physiological plasma concentrations of vitamin C, a water
      soluble congener of vitamin E and reduced glutathione were unable to inhibit the
      oxidizing capacity of uremic plasma. Thus, uremia is associated with accumulation
      of an endogenous oxidizing activity at much higher concentrations than in
      subjects with normal renal function.

PMID- 7564079
TI  - The hemolytic uremic syndrome.

PMID- 7564080
TI  - Glomerular actions of nitric oxide.
AB  - NO, a simple molecule synthesized from L-arginine by NO synthases, has been
      identified to play an important role in cell communication, cell defense and cell
      injury. The half life of NO is very short because NO either reacts with
      superoxide anion (O2-), and/or binds to heme molecules or Fe-S groups present in
      proteins. The biological effects of NO depend on both the concentration of NO at
      the site of action as well as upon the specific location where NO is generated.
      Small quantities of NO are generated by cNOS such as that present in the vascular
      endothelium, while large quantities of nitric oxide are synthesized by iNOS in
      response to cytokines or bacterial products. Within the kidney NO generated by
      endothelial cNOS participates in the regulation of the glomerular
      microcirculation by modifying the tone of the afferent arteriole and mesangial
      cells (Fig. 4). In addition, NO generated by macula densa and the afferent
      arteriole control glomerular hemodynamics via TGF and by modulating renin
      release. Therefore NO is important in the physiologic regulation of glomerular
      capillary blood pressure, glomerular plasma flow and the glomerular
      ultrafiltration coefficient. Through its actions on glomerular pressures and
      flows, NO may also regulate the macro- and micromolecular traffic through the
      mesangium. Chronic NO insufficiency causes hypertension and glomerular damage and
      may be causally involved in the genesis of salt dependent hypertension. Increased
      NO production may be involved in the early pathogenic hemodynamic changes in
      diabetes and in the physiologic hemodynamic responses to normal pregnancy.
      Maintenance of the antithrombogenic properties of the endothelium is another
      important action of NO which inhibits platelet aggregation and adhesion. Large
      quantities of NO such as that synthesized by either glomerular cells or
      macrophages during glomerular inflammation may lead to glomerular injury. A
      better understanding of the physiology and pathophysiology of NO in the kidney
      will lead to the development of new therapeutic avenues.

PMID- 7564081
TI  - Screening for acquired cystic kidney disease: a decision analytic perspective.
AB  - Acquired cystic kidney disease (ACKD) increases the risk of renal malignancy, and
      many authors suggest routine screening of dialysis patients for ACKD and renal
      tumors. However, they have defined neither the target population, the optimal
      screening strategy, the magnitude of its benefit, nor its risk. We used decision
      analysis to evaluate strategies of performing either computed tomography (CT) or
      ultrasound every three years on all dialysis patients and annually on patients
      found to have cysts. We compared these strategies to a strategy of seeking cysts
      and cancer only if these are clinically suspected. The baseline analysis shows
      that both CT and ultrasound may decrease cancer deaths by half for patients with
      a life expectancy of 25 years. Screening for ACKD offers these patients as much
      as a 1.6 year gain in life expectancy. However, for the majority of patients
      beginning renal replacement therapy, age or comorbid disease substantially limits
      life expectancy. For such patients, the gain in life expectancy from an ACKD
      screening program is measured in days. Sensitivity analyses show that the benefit
      of screening depends on the rate of malignant transformation, which needs better
      definition. The gain in life expectancy does not appear to be large enough to
      justify an ACKD screening program for the entire ESRD population. However, for
      the youngest and healthiest patients, a screening program would be of benefit.
      The magnitude of this benefit is uncertain, because the analysis was consistently
      biased in favor of the screening strategies.

PMID- 7564082
TI  - Aquaretic effects of the nonpeptide V2 antagonist OPC-31260 in hydropenic humans.
AB  - The antidiuretic action of arginine vasopressin (AVP) is mediated by interaction
      with renal V2 receptors. A nonpeptide V2 receptor antagonist, OPC-31260, has
      recently been developed. In this study, the effects of OPC-31260 on the excretion
      of water and electrolytes were investigated in normal subjects who were under
      water restriction. Since the clinical circumstances in which a V2 antagonist
      would be useful generally would be in patients with concentrated urine, a
      hydropenic state with nearly maximally concentrated urine was selected as the
      experimental condition. Intravenous injection of OPC-31260 caused an increase in
      urine volume and a decrease in urine osmolality in a dose dependent manner
      without any significant changes in the excretion of sodium and other
      electrolytes. A high dose of OPC-31260 (1 mg/kg body wt) caused free water
      excretion equivalent to that obtained during maximum diuresis after water
      loading, followed by an increase in plasma sodium and AVP concentration.
      Excretion of urea increased transiently during diuresis. Thus, OPC-31260 is
      demonstrated to be the first V2 antagonist which exhibits water diuresis
      (aquaresis) in hydropenic humans with endogenous AVP secretion and maximally
      concentrated urine. The drug will be useful as an aquaretic in the treatment of
      some types of hyponatremia where there is excess AVP and water retention.

PMID- 7564084
TI  - Effect of dialysate temperature on central hemodynamics and urea kinetics.
AB  - Use of cool dialysate is associated with increased intradialytic blood pressure,
      but the hemodynamic mechanism is unknown. Whether changes in dialysate
      temperature affect muscle blood flow, which may the alter the degree of urea
      compartmentalization, also is unknown. We measured hemodynamics and blood and
      dialysate-side urea kinetic indices in nine hemodialysis patients during two cool
      (35.0 degrees C) versus two warm (37.5 degrees C) dialysate treatments. The %
      change in mean arterial pressure was different when using the cool (+6.5 +/- 9.7
      mm Hg) versus the warm (-13.4 +/- 3.6) dialysate (P < 0.01), despite comparable
      amounts of fluid removal. Percent changes in cardiac output were similar with the
      two dialysates, and thus the blood pressure effect was due primarily to changes
      in total peripheral resistance (% delta TPR, cool +26 +/- 13.6, warm +8.6 +/-
      14.5; P < 0.02). During cool dialysate use tympanic membrane temperature changed
      by -0.51 +/- 0.23 degree C, whereas body temperature increased by 0.52 +/- 0.14
      degree C during use of warm dialysate. Measured urea recovery normalized to the
      predialysis urea nitrogen concentration was similar with the two treatments: cool
      31.3 +/- 0.039 liter-1; warm 29.7 +/- 0.021; P = NS. In a second study, post
      dialysis urea rebound values from 15 seconds to 30 minutes, expressed as the
      percent of the post-dialysis SUN, were similar after the two treatments: cool
      11.79 +/- 1.4; warm 12.21 +/- 2.27, P = NS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564085
TI  - Theory and validation of access flow measurement by dilution technique during
      hemodialysis.
AB  - The theory shows that access flow can be measured by the dilution technique by
      reversal of the blood dialysis lines with the venous outlet facing the access
      stream: (1.) with one dilution sensor in arterial line and two injections
      Equation (6); (2.) with two matched dilution sensors on the venous line and on
      the arterial line and one injection Equation (8); (3.) with blood sampling as for
      recirculation measurement using BUN or other methods in Equation (12). In all
      cases, accurate measurement of hemodialysis blood flow is required. The results
      of this bench validation demonstrate that dialysis blood flows, in the clinical
      range of 200 to 350 ml/min or more, create good mixing conditions in a vascular
      access model. Accurate measurements are provided for all clinically significant
      ranges of access flows, needle positions, and vascular access inner diameters.
      This simple, non-invasive, and inexpensive technique shows great promise for
      routine diagnosis of vascular access failure in hemodialysis patients.

PMID- 7564083
TI  - Oxidation of low density lipoproteins from patients with renal failure or renal
      transplants.
AB  - Peroxidation of low density lipoproteins (LDL) may be involved in the development
      of atherosclerosis which is prevalent in patients with chronic renal failure and
      renal transplant recipients. We determined the copper ion catalyzed oxidation in
      vitro, vitamin E content, and chemical and fatty acid composition of LDL isolated
      from 38 patients with renal disease and 15 healthy subjects. Also the acute
      effect of hemodialysis treatment on LDL oxidation variables was tested. The lag
      time in conjugated diene formation during oxidation was significantly (P = 0.011)
      shorter in LDL from renal transplant recipients (66 min, N = 18) mainly due to
      significantly (P < 0.05) shorter times in women (47 min, N = 7), compared with
      healthy subjects (83 min, N = 15), patients on hemodialysis (91 min, N = 13) and
      patients treated by continuous ambulatory peritoneal dialysis (CAPD) (82 min, N =
      7). The maximum rate and the extent of LDL oxidation were significantly (P <
      0.01) lower in all patients with renal disease compared with healthy subjects.
      The triglyceride content of LDL was significantly (P < 0.001) higher in women
      with kidney grafts (7.3%) compared with levels in the corresponding men (5.3%)
      and healthy women (5.0%), and was correlated significantly with the lag time in
      LDL oxidation in renal transplant recipients (Spearmans r = -0.502, P = 0.034).
      The percentage oleic acid in LDL was significantly higher (P = 0.002) and the
      percentage linoleic acid was significantly lower (P = 0.046) in patients with
      renal disease, and may largely account for their lower rates and extent of LDL
      oxidation. Levels of the LDL oxidation variables and organic lipid peroxide
      content of LDL were not significantly different before and after hemodialysis and
      24 hours later. These results suggest that LDL from women with renal transplants
      may be abnormally susceptible to oxidation possibly due to increased triglyceride
      content.

PMID- 7564086
TI  - Chronic renal allograft rejection can be predicted by area under the serum
      creatinine versus time curve (AUCCr).
AB  - Acute rejection is the most important single risk factor for chronic renal
      allograft rejection. Numerical quantitation of rejection episodes does not take
      into account the intensity and length of these episodes, both of which may
      contribute to the severity of chronic rejection. We propose a single numerical
      parameter for the frequency, intensity and length of acute rejections, the "Area
      Under the Serum Creatinine versus Time Curve" (AUCCr) using renal allografts
      between inbred rat strains. Twenty-seven renal transplantations were performed
      from the DA to WF rat strain. The rats were immunosuppressed with 5 mg/kg body
      weight of CyA injected s.c. for 1, 2, 3 and 12 weeks, resulting in differing
      numbers (0-4) of biopsy-confirmed acute rejections of varying intensity (s-cre:
      100-448 mumol/L) and length (3-24 days), all of which were reversed with
      additional CyA treatment. The intensity of chronic changes in graft histology was
      quantitated using the "Chronic Allograft Damage Index" (CADI). End-point
      transplant function was quantitated as level of serum creatinine at sacrifice.
      The AUCCr from 0 to 3 weeks (AUCCr0-3), encompassing the recovery period after
      operation, free of rejections, did not correlate with the CADI (r = 0.230, P =
      0.249). All AUCCr from 3 weeks onwards correlated with the CADI. The best
      correlation with the CADI was obtained with AUCCr from 3 to 12 weeks (AUCCr3-12)
      (r = 0.922, P = 0.0001). This interval coincides with the timing of all acute
      rejection episodes. AUCCr3-12 correlated equally well to end-point transplant
      function (r = 0.890, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564087
TI  - The pathogenesis of parathyroid gland hyperplasia in chronic renal failure.

PMID- 7564088
TI  - Potential role of IGF-1 in parathyroid hormone-related renal growth induced by
      high protein diet in uninephrectomized rats.
AB  - Recent studies indicate that parathyroidectomy (PTX) prevents the progression of
      kidney damage due to high protein diet in the subtotal nephrectomized rat model
      of chronic renal failure. Associated with this protection, the difference in the
      renal "compensatory" growth induced by high (HPr) as compared to normal protein
      diet (NPr) is completely abolished by PTX. To understand the physiological
      mechanism responsible for this protection, the changes in both circulating level
      and kidney content of IGF-1, a growth factor capable of influencing renal
      "compensatory" growth, was analyzed after unilateral nephrectomy (UNX). In UNX
      rats, HPr as compared to NPr diet given for five days significantly increased the
      kidney/body weight ratio (0.48 +/- 0.01%, N = 11 vs. 0.44 +/- 0.01%, N = 11, P <
      0.005) and the plasma level of IGF-1 (365 +/- 10 ng/ml vs. 306 +/- 10 ng/ml, P <
      0.001). In UNX rats fed HPr, PTX completely abolished the renal "compensatory"
      growth (0.38 +/- 0.02%, N = 7, P < 0.001) and the increased plasma level of IGF-1
      (246 +/- 14 ng/ml, N = 7, P < 0.001). In PTX-UNX rats treated with physiological
      doses of 1,25-dihydroxyvitamin D3 which nearly normalized the calcemia, the renal
      growth and the increased plasma level of IGF-1 induced by HPr were restored
      towards those recorded in SHAM-UNX rats fed the HPr diet. Similar effects were
      observed in PTX-UNX rats in which the plasma calcium concentration was increased
      by the chronic administration of a retinoid derivative, used as an agent where
      the calcemic effect is essentially mediated by a stimulation of bone
      resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564089
TI  - Glomerular hemodynamic responses to pregnancy in rats with severe reduction of
      renal mass.
AB  - These studies investigate glomerular hemodynamic responses to pregnancy in rats
      with 5/6th reduction of renal mass of four weeks duration. Both preglomerular and
      efferent arteriolar resistances (RA and RE) fell significantly at midterm
      although single nephron glomerular filtration rate (SNGFR) and glomerular plasma
      flow (QA) were unchanged versus virgins. In late pregnant rats with reduction of
      renal mass, the gestational fall in RA and RE was maintained and GFR, RPF, SNGFR
      and QA were higher compared to virgins. The gestational renal vasodilation was
      prolonged in this model of hypertension versus normals and a peripheral
      vasodilation is also indicated by the late fall in blood pressure. In virgins
      with 5/6th reduction of renal mass, PGC is elevated but in pregnant rats PGC fell
      towards term. The value of Kf was doubled in late pregnancy compared to virgins.
      All three groups of rats with reduction of renal mass showed similar proteinuria
      and similar levels of focal glomerular sclerosis, suggesting that pregnancy did
      not exacerbate the glomerular damage in this model of hypertension and renal
      disease. A decrease in hematocrit in late pregnancy compared with both virgin and
      midterm pregnancy indicated a plasma volume expansion. We conclude that when
      superimposed on hypertension with glomerular damage due to 5/6th reduction of
      renal mass, pregnancy induced gestational renal and peripheral vasodilation and
      plasma volume expansion. Since pregnancy was antihypertensive and lowered PGC,
      there was no hemodynamic basis for pregnancy-associated exacerbation of damage in
      this model of glomerular injury.

PMID- 7564090
TI  - Insulin-like growth factor I induces mesangial proliferation and increases mRNA
      and secretion of collagen.
AB  - Insulin-like growth factor I (IGF-1) is a peptide growth factor that is
      synthesized in cultured mesangial cells and induces hyperplasia. We tested
      whether incubation with IGF-1 at concentrations of 7 nM, 70 nM, and 350 nM
      stimulates mesangial cell extracellular matrix mRNA and protein levels, and
      whether it influences mesangial cell growth. Mesangial cells incubated with IGF-1
      demonstrated a statistically significant increase in procollagen alpha 1(I) (100
      +/- 13% vs. 147 +/- 12%, 154 +/- 10%, and 173 +/- 21%) and alpha 1(IV) 100 +/- 9%
      vs. 112 +/- 9%, 125 +/- 8%, and 172 +/- 28%) mRNA. Furthermore, IGF-1 also
      stimulated a statistically significant increment in alpha 1(IV) mRNA in isolated
      glomeruli when measured by Northern hybridization and corroborated by in situ
      hybridization experiments. In addition, mesangial cells incubated with IGF-1
      induced a statistically significant increase in both secreted and cell associated
      type I (secreted: 100 +/- 5% vs. 127 +/- 9%, 148 +/- 5%, 178 +/- 11%; and cell
      associated: 100 +/- 19 vs. 132 +/- 17%, 198 +/- 24%, and 314 +/- 17%) and type IV
      (secreted: 100 +/- 19% vs. 138 +/- 11%, 192 +/- 17%, 379 +/- 16%, and cell
      associated: 100 +/- 8% vs. 139 +/- 10%, 206 +/- 16%, 310 +/- 15%) collagen. Thus,
      mRNA and collagen levels increased in a dose dependent fashion after incubation
      with IGF-1. Furthermore, IGF-1 stimulated hyperplasia but not hypertrophy in this
      in vitro system. These data suggest that IGF-1 may contribute to glomerular
      sclerosis by increasing mesangial matrix production as well as proliferation.

PMID- 7564091
TI  - Bicarbonate transport in collecting duct segments during chloride-depletion
      alkalosis.
AB  - Renal correction of chloride-depletion alkalosis (CDA) by chloride replacement
      results in bicarbonate secretion in the cortical collecting duct (CD) and urinary
      bicarbonate excretion. To assess the participation of the more distal segments of
      the CD, we determined net total CO2 transport in the outer medullary (OMCD),
      initial (IMCDi) and terminal (IMCDt) inner medullary CD segments obtained from
      Sprague-Dawley rats with normal acid-base balance (NML) or with CDA produced by
      peritoneal dialysis. Tubules were bathed and perfused with isotonic solutions
      containing Cl 110 mM and HCO, 25 mM. Net total CO2 transport was decreased in all
      segments: OMCD 22.1 +/- 4.2 to 9.2 +/- 2.0; IMCDi 38.1 +/- 4.6 to 9.3 +/- 1.7;
      IMCDt 6.7 +/- 1.2 to -0.5 +/- 0.4 pmol/min/mm tubule length. Perfusion rates,
      tubule lengths, and transepithelial voltages did not differ between groups in any
      segment. These data show that all CD segments beyond the cortical segment
      decrease bicarbonate reabsorption during CDA. This permits the bicarbonate
      secreted by the cortical CD to be excreted, and is likely an important mechanism
      for the correction of CDA.

PMID- 7564092
TI  - FK 506: effects on glomerular hemodynamics and on mesangial cells in culture.
AB  - FK 506 is a new immunosuppressive drug that, like cyclosporine A (CsA), presents
      nephrotoxicity. Glomerular hemodynamic studies showed that acute FK 506 infusion
      (N = 9, 3 mg/kg body wt, i.v. in bolus) caused a 57% reduction in glomerular
      filtration rate (GFR) (0.74 +/- 0.03 to 0.32 +/- 0.02 ml/min, P < 0.05) and a 40%
      reduction in single nephron glomerular filtration rate (SNGFR; 43.0 +/- 5.2 to
      26.0 +/- 2.5 nl/min, P < 0.05) due to a 25% reduction in glomerular plasma flow
      rate (QA) (133.4 +/- 19.8 to 99.8 +/- 12.0 nl/min) and a 22% reduction in
      glomerular ultrafiltration coefficient (Kf; 0.1009 +/- 0.0203 to 0.0790 +/-
      0.0130 nl/sec. mm Hg). After 10 days of FK treatment (N = 8, 0.6 mg/kg body wt,
      i.p.), we observed a reduction of 23% in GFR (0.97 +/- 0.02 to 0.75 +/- 0.04
      ml/min, P < 0.05) and of 23% in SNGFR (37.9 +/- 3.0 to 29.1 +/- 1.9 nl/min, P <
      0.05) due to a 42% reduction in Kf (0.1486 +/- 0.0101 to 0.0870 +/- 0.0110
      nl/sec.mm Hg, P < 0.05) and a 38% reduction in QA (117.6 +/- 10.2 to 73.5 +/- 6.1
      nl/min, P < 0.05). The latter was consequent to the increment of 72% in total
      arteriolar resistance (RT) (3.1 +/- 0.2 to 5.2 +/- 0.5 +/- 0.5 10(10).dyn.sec.cm
      5, P < 0.05). Thus, the pattern of FK 506 effect on glomerular hemodynamics was
      similar in both acute and chronic treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564093
TI  - Growth hormone and nutrition interact to regulate expressions of kidney IGF-I and
      IGFBP mRNAs.
AB  - The effects of growth hormone (GH) and fasting on renal insulin-like growth
      factor-I (IGF-I) and IGF-binding proteins (IGFBP)-1, -2, -3, -4, -5 were examined
      in spontaneous dwarf rats (SDR) which have a complete and specific lack of GH
      among pituitary hormones. Renal expression of the mRNA which encodes IGF-I was
      reduced in these rats, and IGFBP-1 and IGFBP-4 were found to be elevated.
      Administration of GH restored expression of IGF-I and IGFBP-1 mRNA, suggesting
      that GH is, among other pituitary hormones, more specifically associated with
      renal expression of these genes. The elevation in the IGFBP-4 mRNA level,
      however, was not attenuated by GH administration, indicating that this hormone
      may not be directly related to the regulation of expression of this gene. Fasting
      for 48 hours resulted in a reduction of IGF-I mRNA and an increase in IGFBP-1
      mRNA in SDRs as well as in normal rats, suggesting that a cause other than a
      reduced serum GH is responsible for these fasting-induced changes. Fasting
      resulted in little change in levels of other IGFBP-2, -3, -4, -5 mRNAs. When
      these results were compared with those obtained using liver, IGFBP mRNA
      expression was shown to be regulated differently in different tissues. Based on
      our finding that IGFBP-1 modulates the mitogenic action of IGF-I, a full
      understanding of nutrition-related growth processes in the kidney must take this
      relationship into consideration as well as that which exists between GH and IGF
      I.

PMID- 7564094
TI  - Protease resistance and binding of Ig light chains in myeloma-associated
      tubulopathies.
AB  - Kidney tubule dysfunction and lesions are frequent complications of myeloma,
      related to unknown properties of the monoclonal light chain. We have analyzed
      protease sensitivity and binding properties of urinary light chains from four
      patients with Fanconi's syndrome, 12 with cast nephropathy, and four control
      patients without myeloma-associated tubulopathy. All light chains were normal
      sized, monomeric and/or dimeric, and none was N-glycosylated. Kinetic studies of
      light chain digestion by pepsin and the lysosomal enzyme cathepsin B showed the
      generation of a protease-resistant 12 kDa fragment, corresponding to the V domain
      of the kappa chain in the four Fanconi's syndrome patients; in two out of four
      the V domain was also completely resistant to trypsin. Western and dot blots
      revealed similar patterns of reactivity of light chains from patients with the
      Fanconi's syndrome towards other light chains. Properties of cast-nephropathy
      light chains were more heterogeneous but clearly differed from those of Fanconi's
      syndrome: (i) 9 out of 12 were of the lambda-type; (ii) only four yielded a
      transient 12 kDa fragment after cathepsin B digestion, but all showed some
      resistance to proteolysis of the entire molecule or a fragment thereof to at
      least one protease, at variance with control light chains; (iii) they displayed
      various patterns of reactivity with other light chains; (iv) 7 out of 12 reacted
      specifically with Tamm-Horsfall protein (THP) by ELISA, in contrast with those of
      Fanconi's syndrome. In one patient who presented with cast nephropathy and the
      Fanconi's syndrome, the light chain exhibited both partial resistance of the V
      kappa domain to cathepsin B and the highest reactivity with THP.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564095
TI  - Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by
      transgenesis with the human Mpv17 homologue.
AB  - The germ line insertion of a defective retrovirus into the Mpv17 gene of mice is
      associated with a recessive phenotype. Mice homozygous for the integration
      develop glomerulosclerosis at a young age. The phenotype resembles human
      glomerulosclerosis in its physiological parameters as well as in histology. A
      human homologue of the Mpv17 gene has been identified, isolated and analyzed. We
      here show that this gene, which has a role in the production of reactive oxygen
      species, can rescue the phenotype of Mpv17 deficient mice when introduced by
      transgenesis. This provides formal proof for the hypothesis that the phenotype is
      caused by the loss of function of the Mpv17 gene. It also provides evidence for
      the functional conservation of the Mpv17 gene in mammals and points to a
      potential role of this gene in human kidney disease.

PMID- 7564096
TI  - Adenine nucleotide and protein kinase C regulation of renal tubular epithelial
      cell wound healing.
AB  - The present studies were done to determine the effect of selected adenine
      nucleotides on healing of wounds made by mechanically denuding areas in confluent
      monolayers of renal tubular epithelial cells. We found that hydrolyzable and
      nonhydrolyzable forms of ATP but not UTP stimulated healing of LLC-PK1 cell
      wounds, while both ATP and UTP promoted healing of MDCK cell wounds, suggesting
      that different subtypes of purinoceptors regulated wound healing in these cells.
      Stimulation of wound healing by ATP was equivalent in control cells and in cells
      in which irradiation suppressed proliferation, suggesting a prominent role for
      cell migration in the healing process. Since ATP receptors are often linked to
      activation of protein kinase C, the effect of a protein kinase C activator (4
      beta-phorbol 12-myristate 13-acetate, PMA) on wound healing was studied. Long
      term (24 hr) exposure to PMA inhibited while short-term (30-120 min) exposure to
      PMA enhanced cell wound healing. Two chemically and mechanistically dissimilar
      protein kinase C inhibitors (calphostin C and chelerythrine) inhibited LLC-PK1
      and MDCK cell wound healing, and calphostin C prevented ATP enhancement of LLC
      PK1 healing. These observations suggest a role for protein kinase C in regulation
      of basal and adenine nucleotide-stimulated wound healing. Adenosine triphosphate
      did not affect cell-cell adhesion of either LLC-PK1 or MDCK cells. Adenine
      nucleotides and PMA enhanced and calphostin C inhibited short-term adhesion of
      LLC-PK1 and MDCK cells to plastic and to other substrates such as fibronectin,
      laminin and collagen type IV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564098
TI  - Human immunodeficiency virus-associated glomerulosclerosis.
AB  - The constellation of nephrotic proteinuria, FSGS, and rapid loss of renal
      function in a patient infected with HIV-1 has been sufficiently widespread and
      well documented to justify identification as a specific renal syndrome, HIV
      associated nephropathy. The position paper of the National Kidney Foundation
      National Institutes of Health task force estimated in 1990 that 10,000 to 15,000
      persons will develop renal disease in association with AIDS [94]. Management of
      these patients is complex, and many will reach ESRD and require dialysis
      treatment, posing additional care problems. Greater understanding of the
      pathogenesis of the renal disease should lead to treatments which will forestall
      the development of HIVAN and possibly other forms of fibrotic renal disease. The
      ultimate eradication of AIDS will consign this renal syndrome to an interesting
      footnote in the history of nephrology. Since that time is still far in the
      future, nephrologists will continue to be faced with the need to diagnose and
      treat HIV-1-infected patients with renal involvement.

PMID- 7564099
TI  - Growth hormone, insulin-like growth factor and the kidney.

PMID- 7564097
TI  - A major role for CD62P/CD15s interaction in leukocyte margination during
      hemodialysis.
AB  - We investigated expression of several antigens on neutrophils and monocytes,
      involved in cell adhesion, from patients hemodialyzed with cellulosic and
      polyacrylonitrile membranes. Among the antigens tested only the expression of
      CD15s and CD11b was significantly increased on neutrophils and monocytes in
      patients dialyzed with cellulosic membranes. No changes occurred with
      polyacrylonitrile membranes. Leukocyte counts from patients dialyzed with
      cuprophane membranes decreased at the same time as expression of cellular CD15s
      increased, resulting in a significant negative correlation at all time points
      tested. No correlation was found between the drop of monocytes and their
      expression of CD11b. When CD15s expression increased on neutrophils and
      monocytes, we observed a concomitant increase of CD62P, a specific selectin of
      activated platelets. When whole blood cells were incubated with complement
      activated serum both antigens increased but not when cells were incubated with
      hrC5a. We also observed that CD61, a platelet phenotypic antigen, was present on
      leukocytes incubated with complement activated serum. At the time when platelet
      leukocyte coaggregates decreased, CD62P expression remained stable on leukocytes,
      suggesting that both neutrophils and monocytes are able to trap either CD62P shed
      by activated platelets or soluble CD62P present in normal human serum. The
      present study documents a major role of P-selectin (CD62P)/sialyl-Lewis x (CD15s)
      interaction in the transient leukocyte margination during hemodialysis.

PMID- 7564100
TI  - Role of platelet activating factor in kidney transplant rejection in the rat.
AB  - Platelet activating factor (PAF) is a potent lipid mediator with a broad range of
      biologic activities. Experimental evidence suggests that PAF plays a role in the
      pathogenesis of a variety of inflammatory processes including allograft
      rejection. In this study, we evaluated the effects of the PAF antagonist BN52021
      on the course of renal allograft rejection in a rat model. Kidneys from ACI
      (RT1a) rats were transplanted into fully allogeneic PVG (RT1c) rat recipients.
      Animals received 60 mg/kg/day of the PAF antagonist or vehicle beginning
      immediately prior to the transplantation procedure. In rats treated with the PAF
      antagonist, allograft GFR and plasma flow were maintained at levels that were
      significantly greater than controls. Despite the improvement in renal allograft
      function, BN52021 had no effect on allograft histomorphology and both groups
      manifested intense inflammatory cell infiltration consistent with acute cellular
      rejection. PAF antagonism reduced urinary excretion of thromboxane metabolites
      and decreased thromboxane production by homogenates prepared from kidney
      allografts. The PAF antagonist had no effect on urinary excretion of
      peptidoleukotriene metabolites or on the production of LTB4 by allografts. These
      data support a role for PAF in the pathophysiology of acute renal allograft
      rejection, and they suggest that the hemodynamic effects of PAF during rejection
      may be mediated through stimulation of thromboxane A2. In view of the beneficial
      effects of PAF blockade in rejection as well as recent reports describing
      efficacy in models of cyclosporine nephrotoxicity, PAF antagonists may have
      clinical applications in human renal allograft recipients.

PMID- 7564101
TI  - Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens
      with sorbinil and galactose feeding.
AB  - Sorbitol plus myo-inositol, betaine and glycerophosphorylcholine (GPC) are
      cellular osmolytes in the mammalian renal medulla. Galactosemia and hyperglycemia
      can cause excessive levels of galactitol or sorbitol in several organs via aldose
      reductase (AR) catalysis. AR inhibitors can reduce these polyols. To examine
      osmolyte responses to polyol perturbations, male Wistar rats were fed normal
      diet, the AR inhibitor sorbinil (at 40 mg/kg/d), 25% galactose, or a combination,
      for 10, 21 and 42 days. All animals at 21 days had higher apparent renal AR
      activity than at 10 or 42 days, possibly providing resistance to sorbinil.
      Sorbinil feeding alone tended to increase urinary, plasma and renal urea levels.
      It reduced AR activity and sorbitol contents in renal inner medulla, though less
      so at 21 days; other renal osmolytes, especially betaine, were elevated.
      Galactose feeding caused little change in renal AR activity, and resulted in high
      galactose and galactitol contents in renal medulla, urine, blood and lens (and
      higher renal Na+ contents at 10 days). Renal sorbitol, inositol and GPC
      decreased, while betaine contents trended higher at all times. Sorbinilgalactose
      feeding reduced renal AR activities and galactitol contents (again less so at 21
      days), urine, blood and lens galactitol, and further reduced renal sorbitol
      contents. At 10 and 21 days it tended to raise renal betaine more, and restore
      inositol (but not GPC) contents to control levels. At 42 days it reduced renal
      and urinary Na+ and galactose, and decreased renal betaine to control levels.
      Under most conditions, total renal (non-urea) organic osmolyte contents (presumed
      to be mostly intracellular) and Na+ plus galactose contents (presumed mostly
      extracellular) changed together such that cell volumes may have been maintained.
      The exception was 10 days on galactose, where total osmolytes appeared too low.
      In galactose-fed animals, urine/plasma ratios suggest some renal galactitol
      efflux, and cellular galactitol probably helps maintain osmotic balance rather
      than cause swelling.

PMID- 7564103
TI  - Human mesangial cell production of monocyte chemoattractant protein-1: modulation
      by lovastatin.
AB  - Macrophages play a critical role in the progression of clinical and experimental
      glomerular injury. Serum-stimulated human fetal mesangial cells in culture
      produce a chemotactic factor that is monocyte-selective. This chemotactic factor
      is most likely monocyte chemoattractant protein-1 (MCP-1) as a monoclonal
      antibody directed against MCP-1, but not an irrelevant antibody, suppressed the
      mesangial cell-derived chemotactic activity. Inhibition of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase by lovastatin resulted in a
      reduction of the mesangial cell-derived chemotactic activity as well as MCP-1
      mRNA expression. The inhibitory effects of lovastatin in the presence of
      exogenous cholesterol were reversed by mevalonate, suggesting a role for
      isoprenoid intermediates of the mevalonate pathway and/or isoprenylated proteins
      in mesangial cell MCP-1 regulation. These findings suggest an additional
      mechanism by which HMG-CoA reductase inhibition in vivo may reduce glomerular
      injury.

PMID- 7564102
TI  - Regulation of manganese superoxide dismutase in glomerular epithelial cells:
      mechanisms for interleukin 1 induction.
AB  - Reactive oxygen species have been implicated as mediators of tissue injury in
      glomerular inflammation. The expression of the antioxidant enzyme, manganese
      superoxide dismutase (MnSOD), was examined in primary cultures of rat glomerular
      epithelial cells (GEC) in response to inflammatory mediators. The results
      demonstrate that GEC respond to interleukin-1 (IL-1) and bacterial
      lipopolysaccharride (LPS) with an increase in MnSOD steady-state mRNA levels. The
      IL-1 alpha-mediated induction of MnSOD mRNA levels was both time- and dose
      dependent. Maximal levels approximately 40-fold above controls, were observed at
      12 hours with 2 ng/ml of IL-1 alpha. MnSOD protein levels were also markedly
      elevated by IL-1 alpha. The induction of MnSOD mRNA by IL-1 alpha required de
      novo transcription as well as some degree of protein synthesis. To elucidate the
      potential intracellular signal that mediates IL-1 alpha-dependent MnSOD
      expression, three classical signaling pathways were examined. We found no
      evidence that MnSOD induction by IL-1 alpha is mediated by either the
      cyclooxygenase or lipoxygenase pathway or via activation of protein kinase C.
      Based on the presence of IL-1 alpha in several forms of glomerular inflammation,
      the observed increase in MnSOD expression by this immunoregulatory cytokine must
      have an important role in the antioxidant defense of glomerular epithelial cells.

PMID- 7564104
TI  - Diversity and variability of smooth muscle phenotypes of renal arterioles as
      revealed by myosin isoform expression.
AB  - The contractility and distensibility of renal arterioles are important in the
      regulation of glomerular filtration. However, little is known regarding the
      characteristics of contractile proteins in these arterioles. Recently it was
      demonstrated that vascular smooth muscles contain two types of myosin heavy chain
      (MHC) isoforms, SM1 and SM2, which are unique molecular markers of smooth muscle
      cell phenotypes. SM1 is constitutively expressed in all types of smooth muscles,
      whereas SM2 exists only in mature smooth muscles. We characterized the expression
      of MHC isoforms as well as the ultrastructural myofilament assembly of renal
      arteriolar smooth muscles in human, rat and rabbit by immunohistochemical
      techniques. SM1 and alpha-smooth muscle actin were localized in both the
      preglomerular vessels (including the afferent arterioles) and efferent
      arterioles, whereas SM2 was present only in the preglomerular vessels. Renin
      producing cells in the afferent arterioles (juxtaglomerular granular cells, JG
      cells) were positive for alpha-smooth muscle actin but negative for SM2. When
      renin synthesis was stimulated, the more proximal afferent arteriolar smooth
      muscles turned renin-positive and SM2 disappeared. Glomerular mesangial cells did
      not show immunoreactivities for SM1, SM2 or alpha-smooth muscle actin. The
      difference in MHC isoform expression in these arterioles was also reflected by
      ultrastructures; the afferent arteriolar smooth muscles contained abundant
      myofilaments including thick filaments, whereas the efferent arteriolar smooth
      muscles had a few myofilaments composed only of thin microfilaments. The JG cells
      displayed a myofilament assembly similar to that in the efferent arteriolar
      smooth muscles. We conclude from these observations that smooth muscles in pre
      and postglomerular arterioles, the glomerular mesangial cells and JG cells differ
      in phenotypes, suggesting that they may have different contractile properties
      which may be critically involved in the regulation of glomerular filtration.

PMID- 7564105
TI  - Cadmium-induced expression of immediate early genes in LLC-PK1 cells.
AB  - To identify molecular mechanisms underlying renal cell damage by cadmium, the
      effect of this heavy metal on the level of immediate early genes (IEGs)
      transcripts in LLC-PK1 cells was studied. Cadmium chloride (CdCl2) induced the
      expression of four IEGs examined, but with differing time courses. The level of c
      fos mRNA peaked at 30 minutes, and then decreased. The levels of c-jun and c-myc
      transcripts reached a maximum at one hour, and remained elevated up to four
      hours. Egr-1 mRNA level peaked at one hour, and returned to the control level by
      three hours. Experiments with cycloheximide and actinomycin D showed,
      respectively, that induction of IEGs by cadmium occurred in a protein synthesis
      independent and transcriptional activation-dependent manner. Cadmium induction of
      c-fos mRNA was reduced markedly by the intracellular calcium chelator, bis-(o
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)-ester
      (BAPTA/AM), and was decreased partially by a protein kinase C (PKC) inhibitor, 1
      (5-isoquinolinylsulfonyl)-2- methylpiperazine (H-7). These data indicate that IEG
      induction by cadmium requires intracellular calcium mobilization and occurs in
      part by a PKC-dependent pathway. Exposure of LLC-PK1 cells to CdCl2 (20 microM
      for 1 to 24 hr) resulted loss of cell viability and DNA fragmentation, which was
      indicative of apoptosis.

PMID- 7564106
TI  - An endothelin-1 mediated autocrine growth loop involved in human renal tubular
      regeneration.
AB  - Renal tubules have the capacity to regenerate following injury. We have
      investigated the possibility that tubular-derived endothelins, acting as
      autocrine growth factors, may be involved in this response in human kidney. ET-1
      immunoreactivity was demonstrated by immunohistochemical staining in proximal
      tubules, distal cortical tubules and medullary collecting ducts of human kidney.
      In cultured human renal proximal tubular cells, RNAase protection assays
      demonstrated the expression of ET-1 and ET-2 mRNA's, and radioimmunoassay,
      following separation of conditioned medium by reverse phase HPLC, showed
      immunoreactive material which co-eluted with ET-1 and ET-2. Competition binding
      studies revealed the presence of at least two types of endothelin receptor: one
      with high and one with low affinity for ET-3 relative to ET-1. Analysis of
      cellular RNA by RT-PCR demonstrated expression of mRNA's for both ETA and ETB
      receptor subtypes. Combined blockade of ETA and ETB receptors (by PD-145065) but
      not that of ETA receptors alone (by BQ-123) blocked the mitogenic effect of
      exogenous or endogenous ET-1 and also profoundly suppressed endogenous ET-1
      synthesis. By contrast, incubation with the ETB receptor agonist, BQ-3020,
      stimulated endogenous ET-1 synthesis. Exposure of the cells to hypoxia (1% O2 for
      16 to 24 hr) resulted in specific up-regulation of ET-1 but not ET-2 gene
      expression. These findings reveal the existence of a hypoxia-inducible, autocrine
      growth system in human proximal tubular cells, which is mediated by ET-1 through
      the ETB receptor, and which could function in vivo as an autoregenerative system
      for restoring tubular integrity after injury. The widespread distribution of ET-1
      peptide in different tubular segment suggests that ET-1 mediated tubular
      regeneration may also occur in other nephron segments.

PMID- 7564107
TI  - Localization of mRNAs for insulin-like growth factor binding proteins 1 to 6 in
      rat kidney.
AB  - Insulin-like growth factor-I (IGF-I) is a peptide growth factor whose activity is
      modulated by interaction with the family of six IGF binding proteins (IGFBPs).
      IGF-I is detected in rat kidney and has metabolic and growth effects. We have
      used in situ hybridization to localize mRNAs for the IGFBPs in rat kidney.
      Messenger RNAs for all six IGFBPs were detected, each with a distinctive
      distribution. IGFBP-1 mRNA was expressed in the distal nephron, from the thick
      ascending limb of the loop of Henle to the cortical collecting ducts. IGFBP-2
      mRNA expression was confined to epithelial cells of the glomeruli and the thin
      limbs of the loop of Henle. IGFBP-3 mRNA was localized to the cortical
      interstitium while IGFBP-4 was the only IGFBP mRNA found in the proximal tubule.
      IGFBP-5 mRNA, the most abundant and widely distributed of the IGFBP mRNAs in the
      kidney, occurred in the glomerular mesangium and the medullary interstitium as
      well as in the epithelial cells of the distal nephron. IGFBP-6 mRNA, the least
      abundant, was expressed mainly in fibroblasts associated with renal blood vessels
      and the ureter. This heterogeneous distribution of the IGFBPs may enable IGF
      action to be regulated by multiple factors in a site-specific manner.

PMID- 7564108
TI  - Complement regulation in the rat glomerulus: Crry and CD59 regulate complement in
      glomerular mesangial and endothelial cells.
AB  - The complement regulators, decay accelerating factor, membrane cofactor protein,
      and CD59 are present in human glomeruli. Crry is the rodent analogue to the
      former two proteins. In this study, we examined complement regulation in cultured
      rat glomerular endothelial cells (GEnC) and mesangial cells (MES).
      Immunoprecipitation of 125I-labeled membrane proteins and Western blotting
      studies were performed with anti-Crry and anti-CD59. In both GEnC and MES, Crry
      was present as 53, 65, and 78 kD proteins. The 20 kD CD59 was apparent in GEnC.
      CD59 was also present in MES, but in relatively smaller quantities. By Northern
      analyses, 1.8 kb CD59 mRNA was present in GEnC as well as in RNA from isolated
      rat glomeruli. mRNA for Crry was present in both GEnC and MES as 2.2 kb species.
      The functional significance of these proteins was evaluated next. Anti-Thy 1.1
      IgG was used to activate the complement classical pathway in MES. To inhibit the
      function of the complement regulators, anti-CD59 and/or anti-Crry F(ab')2
      antibodies were added with anti-Thy 1.1. Inhibition of Crry function led to
      enhanced cytotoxicity, while there was no effect when CD59 function was
      inhibited. The complement alternative pathway was studied by adding complement in
      Mg-EGTA buffer. Inhibition of Crry led to productive alternative pathway
      activation, which was accentuated by anti-CD59 when Crry was incompletely
      inhibited. Alternative pathway regulation was also evaluated in GEnC. Inhibition
      of CD59 function alone had no effect in GEnC, while inhibition of Crry led to
      significant cytotoxicity from alternative pathway activation. Under conditions in
      which Crry was inactive, inhibition of CD59 further enhanced cytotoxicity.
      Therefore, Crry is present in both GEnC and MES and restricts the complement
      alternative pathway in both cell types. Crry also regulates the classical pathway
      in MES. CD59 is present and functionally active in GEnC, while it appears to have
      a minor role in MES.

PMID- 7564109
TI  - Protein kinase C signals thromboxane induced increases in fibronectin synthesis
      and TGF-beta bioactivity in mesangial cells.
AB  - Previous studies have demonstrated that thromboxane (TX) stimulates matrix
      protein synthesis in mesangial cells (MC), and that this action is signalled by
      receptor mediated activation of protein kinase C (PKC). In the present study, we
      examined the hypothesis that activation of PKC by TX signals increases in
      transforming growth factor beta (TGF-beta) bioactivity, which in turn induces
      enhanced matrix protein synthesis. In cultured rat MC, the TXA2/prostaglandin
      endoperoxide analogue U-46619, but not exogenous human platelet TGF-beta 1,
      activated PKC as reflected by enhanced in situ phosphorylation of MARCKS protein,
      an endogenous substrate of PKC. U-46619 and TGF-beta 1 stimulated fibronectin
      (Fn) synthesis in MC, as shown by [35S]methionine incorporation into
      immunoprecipitable Fn. Pan-specific rabbit anti-TGF-beta antibody blocked the
      increases in Fn synthesis induced by exogenous TGF-beta and those induced by U
      46619 at 24 to 72 hours after addition. Anti-TGF-beta antibody did not block the
      small increases in FN synthesis observed six hours after addition of U-46619,
      suggesting that this acute response was not dependent on TGF-beta. Anti-TGF-beta
      antibody also failed to block activation of PKC by U-46619. U-46619 and 50 nM of
      the PKC agonist phorbol dibutyrate (PDBu) significantly increased both the active
      fraction and total (latent plus active) TGF-beta in MC culture media, as assayed
      with the mink lung epithelial cell bioassay system.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7564110
TI  - Cyclosporine A induced arteriolopathy in a rat model of chronic cyclosporine
      nephropathy.
AB  - Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone
      marrow, and renal transplantation, and is characterized in humans by striped
      interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar
      arterioles. This last feature is highly specific for cyclosporine injury and has
      been difficult to reproduce in normotensive animal models. Salt-depletion has
      been shown to sensitize rodents to the effects of CsA and accelerate the disease
      process. We conducted sequential studies in chronically salt depleted, pair fed
      rats treated with CsA (15 mg/kg, s.c.) or an equivalent dose of olive oil
      vehicle, and found a histologic lesion associated with CsA that consisted of
      striped cortical interstitial fibrosis, tubular dilatation and atrophy, and
      hyalinization of many afferent arterioles. The arteriolopathy was first detected
      at day 10 with progressive hyalinization of arterioles continuing until
      termination of the study at day 35. The arteriolopathy consisted initially of
      eosinophilic granular transformation of smooth muscle cells comprising afferent
      hilar glomerular arterioles, and progressed to foci of smooth muscle cell
      vacuolization and accumulation of discrete hyaline deposits in vessel walls.
      Electron microscopy demonstrated marked accumulation of typical renin granules
      throughout the smooth muscle cell cytoplasm, corresponding to the eosinophilic
      granular transformation revealed histologically. Immunocytochemistry confirmed
      the up-regulated production of renin in these vessels. This study documents a
      rodent model for CsA arteriolopathy and CsA-associated interstitial fibrosis that
      strikingly reproduces the most characteristic nephropathic effects of
      cyclosporine found in human patients treated with this agent.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7564112
TI  - Ischemia-induced changes in cell element composition and osmolyte contents of
      outer medulla.
AB  - The effect of 60 minutes of ischemia and subsequent reflow on cell electrolyte
      and water homeostasis in the rat renal outer medulla was studied by determining
      sodium, potassium, chloride and phosphorus concentrations and dry weights in
      individual tubule cells using electron microprobe analysis. HPLC was employed to
      measure glycerophosphorylcholine, betaine, inositol and sorbitol, as well as
      several free amino acids in cortical and outer medullary tissue. Ischemia caused
      cell sodium and chloride concentrations to rise and cell potassium and phosphorus
      concentrations and cell dry weights to fall. These changes were most pronounced
      in the proximal straight tubule (PST) cells, less in thick ascending limb (MAL)
      and outer medullary collecting duct (OMCD) dark cells and barely noticeable in
      OMCD light cells. Except for some PST cells these changes were almost completely
      reversed 60 minutes after reintroducing blood flow. After 24 hours of reperfusion
      the number of PST cells exhibiting deranged electrolyte homeostasis was greatly
      increased. The contents of glycerophosphorylcholine, betaine or inositol in the
      cortex and outer medulla were not affected immediately following ischemia. After
      24 hours of reperfusion, the cortical contents of osmolytes were still normal,
      while outer medullary contents were reduced. Except for low glycine contents, the
      ischemia-induced changes in amino acid contents were reversed after 24 hours of
      reflow in the cortex, whereas in the outer medulla aspartate, glycine and taurine
      contents were diminished. These results indicate increasing manifestation of PST
      cell injury in the reflow period. The defective re-accumulation of organic
      osmolytes and free amino acids in the outer medulla during reflow may reflect
      reduced interstitial tonicities, or may be due to inappropriate cellular uptake,
      synthesis or/and release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564111
TI  - Cellular proliferation and macrophage influx precede interstitial fibrosis in
      cyclosporine nephrotoxicity.
AB  - Chronic cyclosporine (CsA) nephrotoxicity is a major complication of solid organ
      transplantation, and is characterized histologically by striped
      tubulointerstitial fibrosis, tubular atrophy, and hyalinization of the afferent
      arteriole, a highly specific finding in cyclosporine injury. The salt-depleted
      rat model of chronic cyclosporine nephropathy mimics these lesions in humans. We
      conducted sequential studies of this model in groups of pair fed rats (N = 6)
      treated with CsA (15 mg/kg, s.q.) or an equivalent dose of olive oil.
      Proliferation of tubular and interstitial cells was documented early in the
      medulla by day 5 (3.2 +/- 2.1 vs. 0.81 +/- 0.4 cells/HPF in CsA vs. control, P <
      0.02), and was maximal in areas of interstitial fibrosis by day 35 (7.9 +/- 3.7
      vs. 0.52 +/- 0.2 cells/HPF in CsA vs. control, P < 0.005). The interstitial
      fibrosis was associated with a significant macrophage influx by day 35 (13.9 +/-
      3.5 vs. 1.5 +/- 0.32 cells/HPF, CsA vs. control, P < 0.005), which correlated
      with increased cortical tubular staining for the macrophage adhesion protein,
      osteopontin. Elevated serum creatinine correlated with interstitial fibrosis at
      day 35 (0.85 +/- 0.11 vs. 0.40 +/- 0.03 mg/dl Cr, CsA vs. control, P < 0.005) by
      linear regression (r = 0.9, P < 0.05). Medullary proliferation and interstitial
      fibrosis correlated with decreased tubular concentrating ability, and higher
      urinary volume. Cortical interstitial fibrosis was maximal at day 35 and was
      associated with an increase in type I and type IV collagen deposition, while
      tubular injury was associated with increased vimentin expression. Tubular
      interstitial cells also expressed increased vimentin early in the medulla (day
      10) and later in the cortex. Both groups remained normotensive despite
      significantly elevated juxtaglomerular (JG) apparatus renin expression in CsA
      treated animals, implicating the intrarenal-renal renin-angiotensin system in
      this disease. We conclude that cyclosporine nephrotoxicity is associated with
      early tubular and interstitial cell proliferation, and a significant macrophage
      influx that precedes the development of cortical interstitial fibrosis and
      afferent arteriolar hyalinosis. These early cellular changes correlate with
      functional abnormalities including decreased creatinine clearance (CCr) and
      decreased medullary concentrating ability, which stabilized despite progressive
      fibrosis. These cellular events may be important in the pathogenesis of chronic
      CsA nephrotoxicity.

PMID- 7564113
TI  - Inhibition of the CD40-CD40ligand pathway prevents murine membranous
      glomerulonephritis.
AB  - Several forms of glomerulonephritis are induced by antibodies against self or
      foreign antigens. Normal B lymphocyte antibody production requires T cell
      costimulatory signals provided in part by T cell surface expression of
      gp39/CD40ligand (CD40L) that engages the B cell receptor CD40 and induces B cell
      differentiation and immunoglobulin class switching. We assessed the effect of
      disrupting the CD40L-CD40 costimulatory pathway, using a CD40-Ig fusion protein,
      on the development of membranous glomerulonephritis (MGN) in the mouse. MGN is
      induced by mouse antibodies that recognize and bind to exogenously administered
      rabbit anti-mouse renal tubular brush border (RbAMBB) IgG immobilized in the
      glomerular capillary wall. MGN did not occur in nude mice, showing the need of
      the T cell function. C57Bl/10 mice immunized with RbAMBB and treated with CD40-Ig
      fusion protein displayed a delayed autologous response and absence of MGN
      lesions, while control fusion proteins failed to prevent the development of the
      disease. These observations provide evidence that disruption of the CD40-CD40L
      costimulatory pathway can prevent the development of MGN by suppressing T cell
      dependent antibody production.

PMID- 7564114
TI  - Epidemic aluminum intoxication in hemodialysis patients traced to use of an
      aluminum pump.
AB  - This study was designed to identify the source, risk factors, and clinical
      consequences of an outbreak of aluminum intoxication in hemodialysis patients
      using case-control and cohort studies. In 1991, a dialysis center in Pennsylvania
      [Dialysis Center A (DCA)] identified a number of patients with elevated serum
      aluminum levels. All patients receiving dialysis at DCA during January 1, 1987 to
      March 26, 1992 were involved in the study. A case-patient was defined as any
      patient with a serum aluminum level > or = 100 micrograms/liter after > or = 5
      dialysis sessions at DCA. Fifty-nine case-patients were identified. Risk factors
      for elevated serum aluminum levels were receipt of bicarbonate- (rather than
      acetate-) based dialysate, higher number of sessions using bicarbonate dialysis,
      receipt of acid concentrate (used in bicarbonate dialysis) passed through one of
      two electric pumps, and a greater number of sessions using this concentrate. The
      electric pumps had an aluminum casing, casing cover, and impeller. Elevated
      levels of aluminum were found in acid concentrate after passing through a pump.
      Seizures and mental status changes requiring hospitalization were associated with
      aluminum exposure. We found that epidemic aluminum intoxication was caused by the
      use of an electric pump with aluminum housing to deliver acid concentrate used in
      bicarbonate dialysis. This outbreak demonstrates why it is essential to insure
      that all fluid pathways, storage tanks, central delivery systems, and pumps are
      compatible with low pH fluids before converting from acetate to bicarbonate
      dialysis.

PMID- 7564116
TI  - Plasma protein adsorption to highly permeable hemodialysis membranes.
AB  - Although membrane adsorption of plasma proteins is one of several factors
      determining the biocompatibility and mass transfer characteristics of a
      hemodialyzer, this process has not been evaluated rigorously. We performed an
      equilibrium and kinetic analysis of the binding of proteins of differing
      molecular weight to highly permeable membranes of differing hydrophobicity and
      surface change. Hydrophobic, anionic polyacrylonitrile (PAN) and hydrophilic,
      uncharged cellulose triacetate (CT) membrane fragments were incubated in buffer
      containing radioiodinated beta 2-microglobulin (beta 2m) or bovine serum albumin
      (BSA). From an initial solution concentration of 50 mg/liter, both membranes
      adsorbed significantly more beta 2m than BSA at equilibrium (PAN, 352 +/- 30 vs.
      32.1 +/- 2.4 ng; CT, 87.0 +/- 0.6 vs. 30.8 +/- 1.7 ng). These results were
      consistent with membrane pore exclusion of BSA. Comparison of the slopes of the
      equilibrium isotherm lines (concentration range, 0 to 220 mg/liter) showed the
      PAN binding affinity for beta 2m and BSA was 28 and 1.4 times that of CT,
      respectively. In kinetic studies, the approach to equilibrium versus (time)1/2
      was assessed. For all protein-membrane combinations, this relationship was
      linear, consistent with a diffusion-controlled process. This latter
      characteristic permitted the determination of beta 2m membrane diffusivity values
      for both PAN and CT, which were found to be 0.30 and 3.25 x 10(-7) cm2/sec,
      respectively. These data suggest membrane hydrophobicity more significantly
      influences the binding of low-molecular weight proteins than that of pore
      excluded proteins. In addition, these results demonstrate electrostatic membrane
      protein interactions may influence the kinetics of both the adsorption and
      transmembrane mass transfer of plasma proteins.

PMID- 7564115
TI  - Flaxseed: a potential treatment for lupus nephritis.
AB  - Flaxseed is rich in alpha-linolenic acid (alpha-LA) which has anti-atherogenic
      properties, and lignans which are platelet activating factor (PAF)-receptor
      antagonists. These constituents of flaxseed, and its beneficial effects in the
      MRL/lpr lupus mouse prompted us to perform this dosing study in lupus nephritis
      patients. Nine patients were enrolled, eight of whom completed the study. After
      the baseline studies, patients were given 15, 30, and 45 g of flaxseed/day
      sequentially at four week intervals, followed by a five-week washout period.
      Compliance, disease activity, blood pressure, plasma lipids, rheology, PAF
      induced platelet aggregation, renal function, and serum immunology were assessed.
      Flaxseed-sachet count and a significant increase of serum alpha-LA indicated good
      compliance for 15 and 30 g doses. Total and LDL cholesterol, and blood viscosity
      were significantly reduced with 30 g and to a lesser extent 45 g doses. PAF
      induced platelet aggregation was inhibited by all doses. There was a significant
      decline in serum creatinine with 30 and 45 g, and a concomitant increase in
      creatinine clearance with increasing flaxseed dose. Proteinuria was reduced with
      30 g and to a lesser extent with 45 g of flaxseed. Complement C3 was
      significantly elevated by all three doses. CD11b expression on neutrophils, a
      measure of C3bi receptors, was significantly reduced with the 30 g dose. In
      conclusion, 30 g flaxseed/day was well tolerated and conferred benefit in terms
      of renal function as well as inflammatory and atherogenic mechanisms important in
      the pathogenesis of lupus nephritis.

PMID- 7564118
TI  - Gender-dependent disease severity in autosomal polycystic kidney disease of rats.
AB  - The impact of gender on the course of chronic renal failure in polycystic kidney
      disease (PKD) has been under discussion for years. Recently an animal model of
      autosomal dominant PKD in the rat became available allowing this topic to be
      studied. The aim of this study was to evaluate disease severity according to
      gender, and the occurrence of anticipation and/or genetic imprinting. Male and
      female affected PKD rats were crossed with respective Wistar-Ottawa-Karlsburg
      (WOK) rats. From this P generation 26 affected F1 hybrids were obtained, which
      were then backcrossed with WOK rats, resulting in 275 backcrosses (BC
      generation). In BC rats the affected males had a significantly higher kidney
      weight, worse histology and poorer renal function than the females. In the male,
      but not the female rats of the BC generation, transmission from an affected F1
      mother resulted in significantly higher kidney weight, worse histology and poorer
      renal function than when the gene was inherited through an affected father. Since
      at the same time body and kidney weight were higher in the respective unaffected
      males, the previous effect in the affected rats might be due to a growth factor
      transferred by the mother's milk. The sex of the P generation had no such impact
      on these parameters. Thus our data provide no evidence for disease anticipation
      and genetic imprinting (in the classical sense) in the PKD rats, and the
      assumption of a gender-dependent disease expressivity is favored.

PMID- 7564119
TI  - Calcium oxalate monohydrate crystals stimulate gene expression in renal
      epithelial cells.
AB  - Primary or secondary hyperoxaluria is associated with calcium oxalate
      nephrolithiasis, interstitial fibrosis and progressive renal insufficiency.
      Monolayer cultures of nontransformed monkey kidney epithelial cells (BSC-1 line)
      and calcium oxalate monohydrate (COM) crystals were used as a model system to
      study cell responses to crystal interactions that might occur in the nephrons of
      patients during periods of hyperoxaluria. To determine if COM crystals signal a
      change in gene expression, Northern blots were prepared from total renal cellular
      RNA after the cells were exposed to crystals. The immediate early genes c-myc,
      EGR-1, and Nur-77 were induced at one hour. At two to six hours stimulated
      expression of the genes encoding plasminogen activator inhibitor (PAI-1) and
      platelet-derived growth factor (PDGF)-A chain was detected, but constitutive
      expression of urokinase-type plasminogen activator (u-PA) was not altered.
      Expression of connective tissue growth factor (CTGF) was induced at one hour and
      persisted up to 24 hours. The stimulation of gene expression by COM crystals was
      relatively crystal- and renal cell-type specific. Thus the interaction of kidney
      epithelial cells with COM crystals alters expression of genes that encode three
      classes of proteins: transcriptional activators, a regulator of extracellular
      matrix (ECM), and growth factors. Activation of PAI-1 gene expression without a
      change in u-PA favors accumulation of ECM proteins, as does increased expression
      of PDGF and CTGF which can also stimulate fibroblast proliferation in a paracrine
      manner. These results suggest that COM crystal-mediated stimulation of specific
      genes in renal tubular cells may contribute to the development of interstitial
      fibrosis in hyperoxaluric states.

PMID- 7564120
TI  - Mechanisms of hypoalbuminemia in hemodialysis patients.
AB  - Hypoalbuminemia is the most powerful predictor of mortality in end-stage renal
      disease. Since protein-calorie malnutrition can decrease albumin synthesis it is
      assumed that hypoalbuminemia results principally from malnutrition in these
      patients, but albumin synthesis may also be decreased as part of the acute-phase
      response, and hypoalbuminemia can also result from redistribution of albumin
      pools or from albumin losses. We measured albumin synthesis, fractional catabolic
      rate, and distribution from the turnover of [125I] human albumin in six
      hemodialysis patients with plasma albumin less than 35 mg/ml and in six patients
      with plasma albumin greater than 40 mg/ml. Patients with liver disease, HIV, or
      other infection were excluded. Both groups were maintained with high-flux
      polysulfone dialyzers for more than three months. Kt/Vurea and PCR were measured
      during each dialysis (N = 12 to 18/patient). A four-day calorie and protein
      intake was determined by dietary history and long-term nutritional status was
      determined anthropometrically. Measured variables included serum urea,
      creatinine, transferrin, and the positive acute-phase proteins alpha 2-
      macroglobulin, C-reactive protein, ferritin, and IGF-1. Albumin synthesis was
      significantly reduced in the low albumin group. There were no differences in
      dietary intake, body composition, PCR, BUN, creatinine, or Kt/Vurea. Plasma
      albumin concentration correlated negatively with ferritin, C-reactive protein and
      alpha 2-macroglobulin. Albumin synthesis rate correlated negatively with both
      alpha 2-macroglobulin and Kt/Vurea. Both plasma albumin concentration and
      synthesis rate correlated positively with IGF-1, and both were independent of PCR
      and all other nutrition-related variables.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564121
TI  - Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic
      nephropathy.
AB  - Advanced protein glycation has been proposed as a major factor in the development
      of diabetic nephropathy. Advanced glycation end products (AGEs) have altered the
      structure of extracellular matrix component and impaired self association in
      vitro. To elucidate the role of AGEs in the progression of diabetic nephropathy,
      the present study was undertaken to localize glomerular AGEs
      immunohistochemically. Ultrastructural changes of the mesangial matrix were
      analyzed with high resolution scanning electron microscopy. No glomerular AGEs
      staining was noted in normal control kidney specimens, or in tissue from
      glomerulonephritis patients without diabetes mellitus. The mesangium showed a
      positive AGEs staining in advanced stages of diabetic nephropathy, and the most
      characteristic finding was the strong AGEs staining in nodular lesions. By high
      resolution scanning electron microscopy, control and diabetic mesangial matrices
      revealed a meshwork structure composed of fine fibrils (10 nm in width) and
      numerous pores (12 to 13 nm in diameter). In the nodular lesions, however,
      loosening of the meshwork was significant, and the diameter of the pores was
      enlarged (approximately 24 nm). This study provides the first immunohistochemical
      evidence that AGEs are localized in diabetic glomeruli, most notably to nodular
      lesions. Advanced glycation might play a role in the progression of diabetic
      nephropathy through impairment of the assembly of matrix proteins in vivo.

PMID- 7564117
TI  - Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant
      recipients.
AB  - Five years of normoglycemia following pancreas transplantation (PT) does not
      ameliorate glomerular lesions in patients with their own kidneys and with long
      term insulin-dependent diabetes (IDDM) (Lancet 342:1193, 1993). All these
      patients received cyclosporine (CsA) as part of their immunosuppression. Here we
      examined the relationship of CsA dose and blood levels to the presence and
      severity of CsA-associated renal lesions and changes in renal function in these
      PT patients. Renal biopsies were taken before (0) and two and five years after PT
      from 13 non-uremic IDDM patients and were compared with baseline and five year
      biopsies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg/kg/day
      in the first month to 5 +/- 2 in the fifth year post-PT. Creatinine clearance
      (CCr) decreased by 34% at one year post-PT and was stable thereafter, and did not
      change in C. The decline in CCr from 0 to one year was related to CsA blood
      levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction
      [Vv(Int/Cortex)], the index of tubular atrophy, and % sclerotic glomeruli
      increased significantly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001,
      respectively), but did not change in C. There was no significant change from 0 to
      two years post-PT in these lesions, while there was a clear progression from two
      to five years. Mean CsA dose and blood levels in the first year post-PT
      correlated with the increase (delta) in Vv(Int/Cortex) at five years (P < 0.05
      for both).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564122
TI  - Macrophages in childhood IgA nephropathy.
AB  - The role of glomerular macrophages in IgA nephropathy in children was
      investigated using a new monoclonal antibody (KP1) as a probe. The average number
      of glomerular macrophages per patient (ANM/P) was closely correlated with the
      degree of hematuria (P < 0.01) as well as with the degree of leukocyturia (P <
      0.01) in the absence of any correlation with proteinuria, serum IgA levels or the
      interval between the detection of urine abnormalities and renal biopsy. ANM/P was
      significantly higher in patients diagnosed pathologically as having focal and
      diffuse proliferative glomerulonephritis than in patients with minor glomerular
      abnormalities or advanced sclerosis (P < 0.05). Among various types of glomerular
      morphology in individual patients, macrophages predominantly infiltrated
      glomeruli with cell-proliferative lesions despite an absence of any increase in
      glomeruli with minor abnormalities or with sclerosis. Macrophages were mainly
      localized within the capillary lumen in association with endocapillary
      proliferative lesions (tuft necrosis), they accumulated in areas of mesangial
      proliferation, and they were attached to Bowman's capsule in segmental lesions.
      Macrophages were less evident in sclerosis. Furthermore, ultrastructural analysis
      revealed macrophages in the paramesangial areas in close proximity to lytic
      changes in the glomerular basement membrane and effacement of epithelial foot
      processes. In addition, some cases in repeat biopsy shows prolonged or increased
      values of ANM/P after several years of interval in association with progression
      of proliferative lesions. These results suggest that macrophages infiltrate
      glomeruli during acute glomerular inflammation, and that they are involved in
      mesangial proliferation or the development of extracapillary lesions in the
      absence of apparent clinical symptoms. Furthermore, recurrence or prolonged
      infiltration may promote progression of IgA nephropathy.

PMID- 7564123
TI  - Renal proximal tubular epithelium from patients with nephropathic cystinosis:
      immortalized cell lines as in vitro model systems.
AB  - The renal proximal tubule is a major site of injury in a variety of
      congenital/metabolic diseases including nephropathic cystinosis, the most
      commonly known cause of renal Fanconi's syndrome. In this lysosomal storage
      disease there are defects in proximal tubule function within the first few months
      of life. While culture of renal tubular cells from the urine of these patients is
      possible, development of immortalized cell lines would insure large numbers of
      homogeneous cells for studies of renal epithelial cell morphology and
      pathophysiology in this disease. To develop immortalized cells, cystinotic and
      normal proximal tubular cells in culture were exposed to an immortalizing vector,
      containing pZiptsU19 with the temperature sensitive SV40 T-antigen allele
      tsA58U19 and a neomycin resistance gene, and neomycin-resistant tubular cells
      were selected for propagation. Ten clones from cystinotic patients have been
      developed and characterized. All clones express T-antigen at permissive
      temperature (33 degrees C). Immortalized cells have an epithelial morphology and
      grow to form confluent monolayers; doubling times vary from 31 to 86 hours.
      Cystinotic clones are keratin, MDR P-glycoprotein, and alpha-95 kD brush-border
      associated protein positive but Tamm-Horsfall protein negative by
      immunocytochemistry, as are normal proximal tubule cells immortalized with this
      vector. This is consistent with a proximal tubule origin of the cystinotic
      clones. The cystine content of the cystinotic cells is 70 to 160 times that of
      normal renal proximal tubular cells in culture, with most of the cystine
      sequestered in cell lysosomes, confirming that these cell lines express the
      storage defect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564124
TI  - Impaired endothelial function in patients with nephrotic range proteinuria.
AB  - Proteinuria is associated with increased cardiovascular morbidity and mortality.
      Release of nitric oxide by the endothelium has been advanced as an important
      defense mechanism against vessel-wall damage. In the present study we therefore
      tested the hypothesis that proteinuria is associated with a defect in nitric
      oxide-dependent vasodilation, by using venous occlusion plethysmography of the
      forearm in nine patients with nephrotic range proteinuria (> 3.5 g/24 hr) and
      normal renal function (creatinine 83.1 +/- 8.7 mumol/liter), eight patients with
      active glomerulonephritis but normal renal function (creatinine 81.2 +/- 5.4
      mumol/liter) and low range proteinuria (< 1.0 g/24 hr), and ten healthy
      volunteers. We infused L-NMMA (2 mg/min) to inhibit basal nitric oxide
      production, serotonin (0.1, 0.3 and 1.0 ng/kg/min) as an endothelium-dependent
      vasodilator, and nitroprusside (1, 10, 30 and 100 ng/kg/min) as an endothelium
      independent vasodilator into the brachial artery. Administration of L-NMMA
      decreased basal forearm vascular resistance (FVR) by 30 +/- 4% in the nephrotic
      subjects, 38 +/- 4% in the non-nephrotic patients and by 37 +/- 2% in the healthy
      controls (P = 0.15). Upon the highest dose of serotonin FVR decreased in
      nephrotic subjects by 40 +/- 5%, which was less than in non-nephrotic patients
      (56 +/- 3%; P < 0.05) or in healthy controls (55 +/- 3%; P < 0.05). The maximal
      decrease in FVR upon nitroprusside infusion was not different between the groups
      (respectively 84 +/- 2, 84 +/- 3 and 84 +/- 2%). The impaired serotonin-induced
      vasodilation could be attributed to a defect in nitric oxide production, since L
      NMMA almost completely prevented serotonergic vasodilation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7564125
TI  - Steady improvement in renal allograft survival among North American children: a
      five year appraisal by the North American Pediatric Renal Transplant Cooperative
      Study.
AB  - From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative
      Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we
      have analyzed one and two year graft survival by annual cohorts for the years
      1987 through 1991. For the 1987 cohort one and two year graft survival was 72%
      and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively.
      Using a proportional hazards model, and comparing the 1987 cohort to the 1991
      cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of
      practice patterns revealed the following changes which may have been associated
      with this improved graft survival: (1) use of T cell induction antibody, 38% in
      1987 and 67% in 1991 (P < or = 0.001); (2) the increased use of cyclosporine
      (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to
      97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12
      months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991
      (P = 0.03); (4) the decreased use of random transfusions, 54% receiving > 5
      transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use
      of younger cadaver donors between 1987 and 1991 (P < 0.001).

PMID- 7564127
TI  - Kt/V in CAPD by different estimations of V.
AB  - This study compared the measurements of total body water (TBW) by 58% body weight
      (TBW58%), the Watson equation (TBWWV) and bioelectric impedance (TBWBIA) with the
      gold standard, Deuterium oxide (TBWD2O) dilution method in twenty continuous
      ambulatory peritoneal dialysis (CAPD) patients. TBW volumes were highest when
      calculated as TBW58% (42.6 +/- 9.4 liter) and lowest when calculated from TBWWV
      (34.6 +/- 6.8 liter). TBWBIA underestimated TBW when compared to TBWD2O, although
      the difference was not statistically significant (37.1 +/- 9.8 liter and 38.8 +/-
      9.3 liter, respectively). In fact, TBWBIA correlated strongly with TBWD2O (r =
      0.8, P < 0.0001). These discrepancies resulted in significant differences when
      Kt/V week-1 derived from the four methods were compared. To determine the effect
      of percent fat mass on the estimation of TBW by each method, we compared TBW and
      Kt/V week-1 derived from the four methods in nine CAPD patients who had normal
      percent fat mass (Non-Obese) and 11 CAPD patients who had greater than normal %
      fat mass (Obese). In the Non-Obese group, there was close correlation of TBWBIA,
      TBWWV and TBW58% when compared with TBWD2O (r = 0.93, P < 0.001, r = 0.89, P <
      0.01 and R = 0.86, P < 0.01, respectively. Also, Kt/V week-1 derived from TBWBIA,
      TBWWV and TBW58% correlated strongly with Kt/V week-1 from TBWD2O (r = 0.93, P <
      0.0005, r = 0.83, P < 0.01 and r = 0.8, P < 0.01, respectively).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564126
TI  - Expression studies of two vasopressin V2 receptor gene mutations, R202C and
      804insG, in nephrogenic diabetes insipidus.
AB  - Nephrogenic diabetes insipidus (NDI) is a rare X-linked disorder associated with
      renal tubule resistance to arginine vasopressin (AVP). To understand the
      mechanisms of AVP resistance underlying this disorder, we have analyzed the
      vasopressin V2 receptor gene in two unrelated Japanese kindreds with NDI and
      expressed the mutants to characterize their functional properties. Direct
      sequencing revealed two V2 receptor gene mutations: a missense mutation from
      Arg202 to Cys in the third extracellular domain (R202C) and a single base
      insertion (G) in two consecutive GGG triplets (nucleotide 804 to 809) in the
      third cytoplasmic domain, resulting in a frame shift with premature termination
      at codon 258 (804insG). Transient expression study with COS-7 cells showed that
      R202C mutation reduced both binding affinity (15%) and capacity (30%), while
      804insG mutation abolished binding ability. For further evaluation of the binding
      ability of the R202C mutant, we expressed the mutants in Chinese hamster ovary
      (CHO) cells. Although the mutant cell lines produced V2 receptor mRNA comparable
      levels to the wild-type receptor cell lines, R202C mutant cell lines had no
      binding ability. Our results suggest an introduction of a new cysteine residue in
      the extracellular domain and a receptor truncation removing one third of the
      carboxyl terminus could impair ligand binding activity of the V2 receptor through
      a post-transcriptional mechanism, thereby causing AVP resistance in the NDI
      patients.

PMID- 7564128
TI  - ELISA procedures for the quantitation of glutathione transferases in the urine.
AB  - The proximal portion of the human kidney tubular system contains the alpha form,
      while the distal portion contains the pi form of glutathione transferase. These
      cytoplasmic proteins are released into the urine under pathological conditions,
      and an ELISA procedure has been developed for their quantitation. Optimal
      conditions with respect to concentrations of antibody and antigen and incubation
      times were determined. The procedure developed can detect as little as 0.5 ng
      enzyme per ml urine, even in the presence of high concentrations of other
      proteins. No cross reaction between these two isoenzymes or with a number of
      other proteins in the urine was observed. Antibodies interacted with these
      antigens in urine samples in the same manner as they interacted with the purified
      proteins. Storage of samples without loss of antigen required the presence of low
      concentrations of detergent, such as Tween 20, which both stabilized the enzymes
      and prevented their adsorption to the walls of the plastic tubes. The results
      indicate that increased urinary levels of these two enzyme proteins, as
      determined by the ELISA procedure, are useful markers for tubular damage.

PMID- 7564129
TI  - Interleukin-1 in crescentic glomerulonephritis.

PMID- 7564130
TI  - [The Alzheimer test].

PMID- 7564132
TI  - [Effect of calcium dobesilate on progression of diabetic retinopathy].
AB  - BACKGROUND: The increase of platelet aggregation, plasma and whole blood
      viscosity and the decrease of red cell deformability in patients with diabetes
      mellitus may be causative in the development of retinopathy. A therapy
      influencing these factors maybe prevents retinopathy or slows progression.
      MATERIAL AND METHODS: In a clinical and prospective study over 2 years 74
      patients aged 20 to 69 years with a mild background retinopathy were randomly
      assigned to take oral 3 x 500 mg calcium dobesilate (Doxium) or no therapy. Both
      groups did neither differ in demographic nor in laboratory data. In fluorescein
      angiography following characteristics of retinopathy were graded: microaneurysms,
      size and outline of foveal avascular zone, capillary loss and severity of dye
      leakage. Additionally in 15 patients contrast sensitivity, visual fields and
      oscillatory potentials were investigated. RESULTS: The results of the fluorescein
      angiographical characteristics revealed no statistically significant difference
      between both groups. In the oscillatory potentials a significant shortening of
      latency could be found in both groups, but there was no difference between the
      groups. CONCLUSION: A 2-years application of calcium dobesilate has no
      statistically significant influence on the progression of diabetic retinopathy.

PMID- 7564133
TI  - [Thermal photodisruptive laser iridotomy. A retrospective long-term study].
AB  - BACKGROUND: The combined application of the argon- and Nd:YAG-laser for
      iridotomies permits utilizing advantages of both lasertypes and avoiding their
      disadvantages. Long-term results of this thermal-photodisruptive technique have
      so far not been presented, however. PATIENTS AND METHODS: 127 eyes of 70 patients
      with an average age of 67.8 years were retrospectively examined in order to
      obtain information on the longterm results, with special attention being given to
      a potential occlusion of the iris coloboma, potential cataract progression,
      regulation of IOP, the pigmentation of the anterior chamber angle and the
      formation of synechiae. The average time of follow-up was 2.8 years. Laser
      iridotomy had been performed because of glaucoma of the involved eye or at the
      fellow eye or because of a narrow angle situation. RESULTS: The total amount of
      energies applied was 1.1 J on the average for the argon laser and 172.2 mJ for
      the Nd:YAG-laser. Iris colobomas with an average diameter of 500 microns were
      performed on all eyes. Due to this large diameter none of the colobomas was found
      to be occluded. Progression of cataract was seen in 21/127 eyes (16.5%). In some
      of the cases this seemed to be attributable to a lentogene component already in
      starting the acute angle closure glaucoma or the narrow angle situation. IOP was
      within the normal range in 113/127 (89.0%) eyes not additionally treated by any
      other therapy. In 46/74 (62.2%) eyes was increased pigmentation of the chamber
      angle. Synechiae arose in 25/74 (33.8%) eyes. These, however, could be
      significantly reduced by giving mydriatics immediately after the procedure. There
      were no significant differences on comparing laser iridotomy with surgical
      iridectomy. CONCLUSION: Thermal-photodisruptive laser iridotomy has become a
      successful alternative method to the application of either argon- or Nd:YAG-laser
      alone. Since it is a low-risk procedure, it should be regarded as the method of
      choice prior to surgical iridectomy.

PMID- 7564131
TI  - [Confocal scanning laser indocyanine green angiography with the Heidelberg
      retinal angiograph].
AB  - PURPOSE: Indocyanine-green angiography (ICG) has been shown to be a valuable
      adjunctive technique to fluorescein angiography including further delineation of
      choroidal neovascularization in age-related macular degeneration. We report on
      initial clinical experiences with a newly developed infrared confocal scanning
      laser ophthalmoscope. MATERIALS AND METHODS: Fundus and fluorescein angiography
      photographs were obtained in 20 patients with various fundus changes. Confocal
      laser scanning ICG-angiography using the Heidelberg Retina Angiograph (Heidelberg
      Engineering GmbH, Germany) was performed after injection of 25 mg ICG. The
      confocal principle ensures that only light reflected from a defined focal plane
      is detected by the integrated photomultiplier. Excitation wave-length was 795 nm,
      and emission was recorded above 810 nm. About 60% of the emission is detected. An
      additional built-in diode laser (830 nm) allowed fundus visualization prior to
      dye injection. RESULTS: ICG angiography using the scanning laser angiograph
      showed typical findings as previously reported with other systems. The images
      were characterized by high contrast. In addition, the retinal vessels were
      readily visualized in the late phase. By means of the confocal mode different
      layers of the circulation could be visualized. CONCLUSIONS: The findings indicate
      that the confocal scanning angiograph is a useful alternative tool for ICG
      angiography and that it offers similar information obtained by other imaging
      systems. Advantages compared with previous techniques may include high image
      contrast, visualization of retinal vessels in the late phase, lower amount of
      light exposure, direct digital image acquisition and easy practical operation.

PMID- 7564134
TI  - [Postoperative intraocular pressure in the first days after intraocular
      administration of hyaluronic acid solution with different viscosities].
AB  - BACKGROUND: Viscoelastic substances are used in anterior segment surgery to
      reduce tissue trauma and endothelial cell loss and to serve as space maintainer.
      Healon GV (approximately greater viscosity), a hyaluronic acid product with a ten
      times higher viscosity than Healon, is utilized in complicated procedures
      (vitreous pressure, flat anterior chamber, congenital cataracts, etc.) and often
      in phacoemulsification. Intraocular pressure (IOP) rise following incomplete
      removal is a known problem. MATERIALS AND METHODS: A prospective randomized study
      was performed to evaluate the IOP following cataract surgery with Healon or
      Healon GV and different removal times (RT). Forty patients (forty eyes) having
      uncomplicated phacoemulsification with foldable silicone posterior chamber lens
      implantation and identical viscoelastic removal technique were assigned to four
      groups: Healon with 20 or 40 seconds (sec.) RT, Healon GV with 20 or 40 sec. RT.
      All surgeries were performed by the same surgeon using the same technique
      especially for the removal of the viscoelastic. All patients had an identical pre
      and postoperative medication. Intraocular pressures were obtained using
      Goldman's applanation tonometry preoperatively, six, 24, 36, and 48 hours
      postoperatively. RESULTS: The IOP follow-up showed no significant difference
      between the two viscoelastic substances and the two different removal times of 20
      and 40 sec. (t-test). In four patients (two of the Healon-groups, two of the
      Healon GV-groups) the IOP required treatment. On the second postoperative day,
      the same four patients showed IOP lower than 22 mm Hg. The highest mean-IOP (mm
      Hg) in both Healon-groups was obtained at 24 hours postoperatively: 18.5 +/- 3.9
      SD (Healon); 17.3 +/- 5.9 SD (Healon GV). CONCLUSION: The incidence of
      postoperative rise in IOP using high viscosity hyaluronic acid (Healon GV) can be
      minimized by the applied removal technique. Both viscoelastics-despite of higher
      molecular weight and viscosity-can be removed equally from the anterior chamber
      following phacoemulsification and posterior chamber lens implantation utilizing
      IOP as a parameter in vivo.

PMID- 7564135
TI  - [Cogan I syndrome: too often detected too late? A contribution to early diagnosis
      of Cogan I syndrome].
AB  - BACKGROUND: Cogan's syndrome is an uncommon disease characterized by ocular
      inflammation, vestibuloauditory dysfunction and symptoms of systemic disease. The
      etiology is unknown, however there is evidence for an autoimmune pathogenesis.
      The "typical" Cogan's syndrome presents as bilateral interstitial keratitis and
      progressing vestibuloauditory dysfunction. The presence of other inflammatory
      manifestations in addition of keratitis has been termed as "atypical" Cogan's
      syndrome. PATIENTS: We report on six patients presenting with typical as well as
      atypical ocular manifestations between 1982 and 1994. Typically, the illness was
      accompanied by systemic symptoms. Each patient had audiovestibular involvement,
      that was the initial presentation in 4 cases. Vestibular dysfunction often
      preceded hearing loss. Five of our patients not only presented with keratitis but
      also demonstrated signs of ocular inflammation diagnosed as scleritis or
      episcleritis. In two patients these ocular symptoms were the first signs of
      Cogan's syndrome, recurred periodically and did not respond to corticosteroids.
      RESULTS: In 3 patients that were diagnosed early and treatment with
      corticosteroids was initiated early, hearing could be stabilized, in the
      remaining patients total bilateral deafness could not be prevented. CONCLUSION:
      The importance of being aware that vestibuloauditory dysfunction may occur in
      patients with ocular inflammation, and the fact that early immunotherapy may
      prevent the risk of deafness, has to be emphasized.

PMID- 7564136
TI  - [Importance of ocular blood flow in glaucoma].
AB  - BACKGROUND: The vascular factor is becoming increasingly important in the
      pathogenesis of primary open-angle glaucoma. Ocular hypotonia, which is
      indubitably a risk factor in the development of glaucoma, cannot be regarded as
      the sole pathogenic factor. Clinical experience leaves no doubt that some
      patients tolerate a high IOP for prolonged periods of time without ocular damage.
      In others, however, severe glaucoma-related lesions result from slight hypertonia
      or critically low pressure. METHODS: The authors analyze the general factors
      which influence ocular blood flow and increase the deleterious effect of ocular
      hypertonia, and report results relating to the hemodynamic status of a group of
      glaucoma patients prior to and after one year of therapy with beta-blockers. The
      results are analyzed and discussed.

PMID- 7564137
TI  - [Sandwich intraocular lens implant: a concept for aphakia correction in
      children].
AB  - BACKGROUND: In the management of congenital cataracts the correction of aphakia
      is still an unsatisfactorily solved problem. As far as surgical techniques and
      materials are concerned, the implantation of an IOL seems to be justified even in
      younger children; but choosing the refractive power of the lens is somewhat
      difficult regarding the expected growth of the eye. MATERIALS AND METHODS: A new
      type of IOL is presented as a solution for this problem. Being composed of a PMMA
      fashioned optic and haptic it bears a silicone lens which is fastened on top of
      it. The supporting lens is made of PMMA (polymethylmethacrylate) with a biconvex
      surface with modified J-loops. The diameter of the optic is 6 mm, the overall
      diameter is 11 mm. The supplementary lens is made of the same silicone material
      as used for foldable intraocular lenses. Its diameter is 4.5 mm. This additional
      component can be removed from the implanted lens so that the needed reduction of
      refractive power after completed growth of the eye can be performed. The PMMA
      fashioned basic component remains in situ just like a conventional posterior
      chamber lens. The lens was examined using scanning-electron microscopy. Im- and
      explantation was performed in isolated porcine eyes. RESULTS: The high quality of
      the lens could be demonstrated using scanning-electron microscopy. The technical
      feasibility of this concept could be demonstrated on isolated porcine eyes.
      DISCUSSION: Currently the sandwich lens is being tested in animal experiments.
      Our special interest is focussed on biocompatibility, formation of secondary
      cataract, biological reactions in the interface and the possibility of atraumatic
      explantation of the silicone lens.

PMID- 7564138
TI  - [Computer program for improved diagnostic coding in ophthalmology based on the
      expanded ICD 10].
AB  - BACKGROUND: The coding of ophthalmological diagnoses is a long-standing problem
      that has recently been highlighted by the planned introduction of ICD 10.
      METHODS: Using an alphanumerical classification system for the first time, ICD 10
      offers the space needed for necessary expansion without leading once again to
      dislocations in the numbering system. The FoxPro 2.5 database system was used to
      create a program based on an expanded ICD 10 that can be applied from DOS and
      Windows. RESULTS: ICD 10 was expanded by the addition of a numerical fifth digit,
      thus increasing the number of classifiable ophthalmological disorders by a factor
      of 4.2 from 390 to 1635. The new program greatly facilitates the handling of this
      substantial amount of data. CONCLUSIONS: The enhanced diagnosis coding achieved
      with the expanded ICD 10 permits nosologically exact statistics to be kept for
      use as a basis for further scientific work.

PMID- 7564139
TI  - [Corneal markers for continuous keratoplasty sutures].
AB  - BACKGROUND: In penetrating keratoplasty adaptation of wound edges, mode of
      trephination of both donor and patient cornea and last but not least techniques
      of suture style are the factors determining postoperative astigmatism. A new
      corneal marking device for keratoplasties and epikeratophakias is introduced.
      This marker helps the surgeon both to center the trephine and to perform a
      perfect double running torque antitorque suture. METHODS: The marker has the
      shape of an 8-bite star. It can be stained and printed on the cornea. The cross
      hair of the marker has to be right in the optical center. After trephination we
      fix the graft with temporal single sutures. Then we mark the dried cornea, so
      that an 8-bite star can be printed on the cornea. Now a first 10-0 running suture
      is done. The second continuous suture can be set just in between. In our
      experience it turns out more precisely, if this second running suture is
      previously marked, too. RESULTS AND CONCLUSIONS: After 35 perforating
      keratoplasties performed with this new marking device the mean astigmatism was
      2.0 +/- 0.75 dpt (x +/- sx). Only a prospective, randomized study comparing
      different suture styles with and without star marker can elucidate the definite
      value of this new surgical instrument.

PMID- 7564141
TI  - [Symposium of the Berlin-Brandenburg Ophthalmological Society. Berlin, 3-4
      December 1994. Abstracts].

PMID- 7564140
TI  - [Lymphatic congestion of the conjunctiva after pre-auricular lymph node
      excision].
AB  - PATIENT: A 68-year-old woman presented with massive congestion of lymphatic
      vessels of temporal inferior conjunctiva two months after extirpation of the
      parotic gland for an aciniform epithelioma on the same side. Clinical findings of
      the right and left eye were unremarkable otherwise. The congestion resolved
      spontaneously. METHODS: Patent Blue 2.5% was injected into the subconjunctiva in
      5 mm distance of the limbus. The superior conjunctiva revealed a normal circular
      pattern of lymphatic vessels. In the temporal inferior conjunctiva massively
      congested lymphtic vessels could be demonstrated. This area is normally drained
      by the regional lymphnodes now interrupted by the surgery. CONCLUSION: The
      individual anatomy of the lymphatic vessels may be of significance also in
      filtering surgery. Especially radial conjunctival cuts may interrupt the
      lymphatic vessels. The regional lymphatic drainage from the temporal inferior
      conjunctiva is blocked by massive surgery of the parotic gland.

PMID- 7564142
TI  - [Society of Pediatric Oncology and Hematology--current status].

PMID- 7564143
TI  - [Acute myeloid leukemia in children with Down syndrome].
AB  - Forty-four children, aged between 0.4 and 16.2 years (median 2.0 years) with
      Down's syndrome and acute myelogenous leukemia (AML) including subacute
      megakaryoblastic leukemia (M7) were diagnosed between 1980 and 1986 (group 1, n =
      16) or between 1987 and 1992 (group 2, n = 28). The leukemic blasts from Down's
      syndrome patients often proved difficult to classify. In group 1 the most
      frequent diagnoses were FAB M5 (6 pts.), M6 (3 pts.), in 3 patients the
      morphological diagnosis of M7 can retrospectively be assumed. In group 2, 15 of
      28 patients were classified as M7, in 3 patients based on morphology alone, and
      in the other 12 patients confirmed by immunophenotyping or biopsy. The other
      children in group 2 were classified as: FAB M0 (3 pts.), M1 (1 pt.), M4 (2 pts.),
      M5 (2 pts.), M6 (4 pts.), M6/M7 (1 pt.). Initially, the latter and 10 of the
      patients with M7 presented with < 30% of blasts in the bone marrow. Karyotyping
      in 12 of 13 children frequently revealed numeric abnormalities, particularly
      trisomies involving chromosomes 8 (n = 6), 11 (n = 3), 21 (n = 3) and 14 (n = 1)
      in addition to the constitutional + 21c. Six patients in group 1 received no
      specific treatment, while 10 children were treated according to the protocols AML
      BFM-78 or -83. Four of them are still alive for more than 5 years, two others
      died from infections in remission after 1.0 and 3.8 years. Fourteen of the 28
      patients in group 2 did not receive any chemotherapy (10 with M7), and
      subsequently died.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564144
TI  - Testicular germ cell tumors. Results of the GPO MAHO studies -82, -88, -92.
AB  - The MAHO studies 82, 88 and 92 were cooperative studies for the treatment of
      testicular germ cell tumors in childhood. Between 1992 and 1993 137 Patients were
      registered: 76 suffered from yolk sac tumors (YST), 30 from differentiated
      teratomas (TD), 29 from malignant teratomas of either intermediate (MTI),
      undifferentiated (MTU) or trophoblastic type (MTT) and 2 from seminoma. All
      patients received semicastratio. Chemotherapy was administered to 53 patients
      based on stage and histology. Standard therapy consisted of four courses of
      vinblastine, bleomycin and cisplatinum. However, if viable tumor was suspected
      after two courses delayed laparotomy was performed (7 patients). If there was
      then complete tumor regression, standard therapy was continued (4 pts). If there
      was incomplete tumor response, the patients received a salvage therapy with 3
      courses of VP 16, ifosfamide and cisplatinum (3 pts). Results YST: 73 patients
      had stage I, 3 patients higher stages. 56 were followed according to "watch and
      wait" policy. 9 of these needed a delayed standard chemotherapy, one died. The
      disease free survival of all 76 patients is 98%. TD: 30 patients had stage I. The
      disease free survival is 100%. Malignant teratomas (MTI, MTU, MTT): 13 patients
      had stage I. 8 received adjuvant chemotherapy and 5 lymphadenectomy without
      chemotherapy. All patients survived disease free. 10 patients had stage II and
      received chemotherapy. All patients survived disease free. 6 patients had stage
      III. 3 died. Altogether 26 of 29 patients survived disease free. In summary, the
      probability of disease free survival of all 137 patients suffering from
      testicular germ cell tumors is 97% after a median observation time of 60 months.

PMID- 7564145
TI  - [Prognosis in Ewing sarcoma patients with initial pathological fractures of the
      primary tumor site].
AB  - In this retrospective analysis, data of 52 patients with Ewing's sarcoma or PNET
      with a pathological fracture in the area of the primary tumor were evaluated. All
      patients were treated according to the trials CESS 81, CESS 86 P, CESS 86, CESS
      91 P and EICESS 92 of the German Society of Pediatric Oncology and Haematology
      (GPOH). At the date of evaluation (15. September 1994) all patients had completed
      treatment and had been under observation for at least one year following
      diagnosis. The median follow-up time was 28 months. 22 patients were female, 30
      male. The median age was 12 years. 75% of primary tumors had a volume of > or =
      100 ml. 30 patients presented with fractures in proximal, 12 in central and 10 in
      distal parts of the skeleton. 10 patients had primary metastases. The
      histological definition was Ewing's sarcoma (including atypical Ewing's sarcoma)
      in 43 patients, PNET in 8 and small-cell osteosarcoma in 1 patient. For local
      therapy the patients underwent surgery, definitive radiotherapy or a combination
      of both. The percentage of primary metastases in the group of the patients with
      pathological fractures is comparable to the whole reference group. The present
      analysis focuses on those patients with pathological fractures who had no
      metastases at diagnosis. The relapse-free survival of patients with a
      pathological fracture and no primary metastases is 58%, the overall survival 65%.
      These rates are similar to those of the reference group of protocol patients
      without pathological fractures at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564146
TI  - [Second neoplasms after malignant diseases in childhood].
AB  - Since 1980 the German Registry of Childhood Malignancies has been established. In
      the framework of the long-term follow-up secondary malignancies are reported
      continually to the registry. An additional retrospective inquiry to all treating
      clinicians and principal investigators of clinical trials as well as a link to a
      previously existing pool of secondary malignancies (1) lead to a completion of
      the data. At the registry now 329 patients with second malignant neoplasms have
      been observed. 41.3% of them had been developed the first malignancy before the
      registry started its work in 1980. The most common primary malignancies are acute
      lymphoblastic leukaemia (ALL, 28.6%), brain tumours (12.2%), and retinoblastomas
      (8.8%). Compared to the population of the registry retinoblastomas as a secondary
      malignancy occur in excess (2.5% vs 8.8%). Most common secondary malignancies are
      brain tumours (20.1%), acute non-lymphoblastic leukaemia (13.1%), osteosarcomas
      (10.9%), and thyroid carcinomas (6.1%). Hereby especially for thyroid cancer a
      remarkable deviation from the frequency in the total population of the registry
      (0.2%) is observed. In 3% of the patients a secondary malignancy appears within a
      span of 10 years after the primary malignancy. This is a twentyfold increase
      compared with the cumulative rate of developing a malignancy in the first 10
      years of life. Brain tumours after ALL (8.5%) and after other brain tumours
      (5.8%) and osteosarcomas after retinoblastomas (4.9%) are the most often reported
      combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564147
TI  - Brachytherapy in the combined modality treatment of pediatric malignancies.
      Principles and preliminary experience with treatment of soft tissue sarcoma
      (recurrence) and Ewing's sarcoma.
AB  - Radiotherapy is an integral part in the treatment of soft tissue and Ewing's
      sarcoma in children. By brachytherapy a high dose can be delivered in a
      restricted volume with sparing of normal tissues surrounding the target. Taking
      into account this principle potential benefit brachytherapy may play some role in
      the local treatment especially in children. However, only limited experience with
      pediatric brachytherapy has been reported apart from a few centers, which have
      gained their experience with Low-Dose-Rate (LDR)-brachytherapy. Since 1991 - 12
      patients with soft tissue sarcoma and 6 patients with Ewing's sarcoma were
      treated with High-Dose-Rate (HDR) and Pulse-Dose-Rate (PDR)-brachytherapy at the
      departments of radiotherapy in Munster, Kiel and Vienna. The combined modality
      treatment was performed according to the CWS-86/91, EICESS-92 and CESS/CWS-REZ-91
      protocols. In 8 patients with soft tissue sarcoma brachytherapy was part of the
      recurrence treatment regime, in 4 patients brachytherapy was part of the primary
      treatment alone or in combination with external beam therapy. In HDR-treatment a
      dose of 15 to 43 Gy was delivered in 3 to 16 fractions, in PDR-treatment 13 to 36
      Gy in fractions of 1 Gy/hour. Follow-up is 3-39 months (median 14 months). 7
      patients show no evidence of disease, 9 patients are locally controlled and 3
      patients progressed locoregionally. In 6 patients with Ewing's sarcoma
      brachytherapy was performed intraoperatively as a boost treatment after external
      beam therapy (50-55 Gy), if no wide resection could be achieved within first line
      treatment. A dose of 10-12 Gy was applied in one fraction in a limited volume (20
      50 ccm) at the time of surgery. Follow-up is 13-26 months (median 21 months).
      There is no evidence of disease in all patients, perioperative and subacute
      morbidity was not increased. These encouraging preliminary results with HDR/PDR
      brachytherapy must be further evaluated prospectively and systematically within
      an interdisciplinary approach by some specialized collaborating centers, which
      not only have the equipment (HDR/PDR/(LDR)-brachytherapy) but also can meet the
      complex demands to accumulate the necessary experience.

PMID- 7564148
TI  - [Psychosocial services in pediatric oncology. Results of a country-wide survey].
AB  - 8 years after the beginning of a german state financed project concerning the
      psychosocial care of children with cancer and their families 52 german children's
      oncology units were asked about their present psychosocial staff. The situation
      of psychosocial care in children with cancer is very good, as most of the staff
      are employed on a long term basis, financed by the german health insurance
      companies.

PMID- 7564149
TI  - [Local school attendance by students with cancer during and after therapy].
AB  - The pilot project brought to attention in this study aims to improve social
      integration and reintegration at school of pupils inflicted by cancer. The
      guidelines include an intensive, long-range individual care and accompanied
      visits in the patients' own classes. Conversations are offered by hospital
      teachers and, eventually, by physicians in the classroom proper. This approach
      results in reducing fear, insecurity and ignorance of both school-mates and
      teachers at the school of origin, thus mediating better human implications facing
      children and adolescents involved. The experience attained from over 80 visits in
      schools of origin indicates that these contacts strengthen the patients'
      prospects and reduce their social and school-associated problems in terms of
      promotising their psycho-social conditions.

PMID- 7564151
TI  - [Oncologic after-care--a patient-oriented concept. Basic diagnostic plan for
      pediatric oncology patients].
AB  - With intensive treatment many children and young adults with cancer can be cured
      of their disease. Therefore, the recognition of late effects of therapy will
      become increasingly important. Future concepts of follow-up care in pediatric
      oncology will have to serve two purposes: First, to determine the status of the
      malignant disease with early diagnosis of relapse and second, to recognize
      relevant side effects of treatment. We present a comprehensive approach of follow
      up care which is primarily based on the definition of risk criteria for the
      development of relevant organ toxicity after different treatment modalities. For
      each patient a standardized summary of therapy delivered is documented. According
      to the definition of the risk criteria an individualized schedule for follow-up
      is decided upon. We hope that this structured concept will result in appropriate
      patient care while keeping the diagnostic efforts and costs limited.

PMID- 7564150
TI  - [After-care of children and young adults surviving cancer. Initial
      recommendations by the late sequelae study group].
AB  - An increasing number of children suffering from cancer has been treated
      successfully during the last 25 years using therapy protocols of the Gesellschaft
      fur Padiatrische Onkologie und Hamatologie. The patients had to undergo an
      interdisciplinary treatment modality and a mostly intensive chemotherapy. Late
      effects could result from this approach for the now 20,000 survivors in the
      Federal Republik of Germany. The executive committee of the GPOH founded a
      working group for the detection of late effects stretching over all therapy
      studies. The first report of this group describes a spectrum of relevant late
      effects and proposes investigations for their detection.

PMID- 7564152
TI  - [Severe neuropathy after chemo- and radiotherapy of Ewing sarcoma].
AB  - A 15 year old patient presenting with a lumbar Ewing's Sarcoma was treated
      according to the EICESS-92 pilot study (EVAIA branch). Local therapy consisted of
      definitive irradiation given simultaneously to chemotherapy courses 5 to 7. Close
      to the end of treatment the patient developed progressive peripheral neurologic
      deficits. Such combined toxic treatment side effects are unique and unforeseen in
      the study protocol.

PMID- 7564153
TI  - [Long-term infusion of L-asparaginase--an alternative to intramuscular
      injection?].
AB  - Nine children of the ALL-REZ BFM 87 and 90 trial received L-Asparginase (L-ASP)
      as a continuous infusion for 48-72 hs (i.e. 25 therapy cycles). Seven patients
      had had an allergic reaction towards an i.m. application (i.m., 29 therapy
      cycles). Two further patients got L-ASP initially as continuous infusion. The
      i.m. applications were carried out 19 times with Erwinia and 10 times with E.
      coli-Asparaginase, the continuous infusions 15 times with Erwinia and 10 times
      with E. coli-Asparaginase. In case of four patients continuous infusions of the
      same L-ASP type (E. coli or Erwinia) was well tolerated, after there had been an
      allergic reaction after i.m. application. Allergic reactions after i.m.
      application occurred during 10 courses as local painful erythema, during five
      courses as urticaria, during four courses as a general exanthema during one
      course as difficult breathing and during a further course as drop in blood
      pressure. After continuous infusion of L-ASP urticaria and difficult breathing
      occurred once and a transient exanthema two times. There was no anaphylactic
      reaction in any case. These data show that i.m. application of L-ASP causes no
      life-threatening side effects but allergic reactions (local pain and swelling)
      which clearly impaired general condition. Continuous infusion is a
      pharmacologically equivalent alternative with less impairment of the patients'
      general condition.

PMID- 7564154
TI  - [Phenotypic differences between CD34 positive cells in various transplantation
      tissues].
AB  - Transplantations to restore the hematopoietic system were originally performed
      with cells from the bone marrow (BM) (20) which was considered the only cell
      source comprising repopulating progenitor cells. The discovery that chemotherapy
      induced the mobilization of CD34+ cells into the peripheral blood (PB) (14) gave
      rise to the successful autologous transplantation of PBSC (1, 13). Also cord
      blood (CB) was found to contain considerable numbers of "stem cells", and to date
      at least 42 allogeneic transplantations have been performed with this cell source
      (22, J. Wagner, personal communication). Further investigations led to the
      successful autologous transplantation of positively selected CD34+ cells from BM
      and PB (18), and the latest results indicate that it is promising to transplant
      purified CD34+ cells obtained from cytokine-stimulated donors (4, 10, 15-16).
      Despite such achievements it remains unclear how many "stem cells" are required
      per kg of the recipient and how they are phenotypically characterized. In this
      communication we give examples of typical differences observed by flow cytometry
      and clonogenic assay between the CD34+ cells contained in the different cell
      sources. They may explain why it is not sufficient only to analyze the CD34+ cell
      populations which may represent progenitors of different lineages as well as of
      various states of differentiation. CB CD34+ cells are early myeloid progenitor
      cells with the highest incidence of CFU-mix among the three cell sources. They
      have a high proliferative potential in vitro. They hardly coexpress B cell
      antigens and they are partially negative for CD38.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7564155
TI  - [Residual placental blood and bone marrow as sources of hematopoietic stem cells
      for allogenic stem cell transplantation. Comparative analysis of hematopoietic
      potential].
AB  - Umbilical cord blood (UCB) contains a high number of hematopoietic progenitor
      cells, which can be used for a HLA-identical transplantation. To proof the
      usefulness of this source of stem cells for transplantation we compared the
      cellular composition of 19 specimen of bone marrow of healthy donors (BM) and 23
      of UCB. We determined the cell number, the frequency of CD34+ progenitor cells
      and the CFU-GM as well as the T- and B-cell-subsets by means of flow cytometry
      and in vitro culture methods. The T-cell content was higher in UCB than in BM
      while the B-cell number was lower. The CD34+ progenitor number per ml was 2.9
      fold higher in BM than in UCB, but the frequency and the proliferative capacity
      of the CFU-GM progenitor cells in the CD34+ population was 8.6 fold higher in UCB
      than in BM. First clinical trials have demonstrated the usefulness of UCB for
      allogeneic stem cell transplantation in children. It is possible to harvest 80
      100 ml UCB per placenta containing 1.2 x 10(9) nucleated cells with 9.7 x 10(5)
      (4-15 x 10(5)) CFU-GM.

PMID- 7564156
TI  - [Expression of CD44-standard in 182 primary neuroblastomas].
AB  - 182 untreated neuroblastomas were examined for the expression of the adhesion
      molecule CD44s by immunohistochemistry; all tumors were also tested for
      amplification of the oncogene N-myc by conventional Southern blot analyses.
      Positive CD44s immunoreactivity correlated not with a more favorable prognosis in
      contrast to an absence of CD44s expression in stage dependent or independent
      evaluations. All patients with stage 4S disease (n = 16) expressed CD44s on a
      high level and had an event-free survival probability of 82%. In undifferentiated
      neuroblastoma subgroups could be defined, depending on the expression of CD44s (p
      < 0.01). In 93% of N-myc non-amplified tumors CD44s expression was detected,
      whereas only 62% of N-myc amplified tumors were positive for CD44s expression.
      These results point to CD44s expression as a new histological marker in
      neuroblastoma, having prognostic impact in tumors of undifferentiated morphology.

PMID- 7564157
TI  - Cleavage of BCR/ABL mRNA by synthetic ribozymes--effects on the proliferation
      rate of K562 cells.
AB  - Ribozymes are effective tools for the cleavage of target RNAs in a sequence
      specific way. In chronic myelogenous leukemia (CML) the reciprocal translocation
      of chromosomes 9 and 22 results in the formation of the unique BCR/ABL fusion
      gene which is believed to play a crucial role in the establishment of CML. In
      order to decrease the BCR/ABL gene product we designed short synthetic ribozymes
      and analyzed their effects on the proliferation rate of K562 cells. Ribozymes
      proved to have a higher inhibitory potential as conventional antisense constructs
      of comparable nucleotide sequence.

PMID- 7564158
TI  - [Serum concentrations of insulin-like growth factors (IGF)-I and IGF-II and IGF
      binding proteins (IGFBP)-2 and IGFBP-3 in 49 children with ALL, NHL or solid
      tumors].
AB  - The IGF regulatory system has been shown to mediate mitogenic effects during
      normal growth and tumor proliferation. The bioavailability of both IGF-I and IGF
      II is regulated by at least six specific IGF binding proteins (IGFBPs). Whereas
      IGFBP-3 is the main IGFBP postnatally, IGFBP-2 is the predominant IGFBP during
      fetal life. In addition, IGFBP-2 is expressed in a range of tumor cell lines. In
      order to investigate the IGF regulatory pathway in malignancies we analyzed by
      RIA serum samples of 49 children with leukemia, Non-Hodgkins' Lymphoma (NHL) or
      solid tumors at the time of diagnosis. Serum concentrations of IGF-I (mean/range:
      -2.4/0.3 to -9.9 SDS), IGF-II (-2.5/0.2 to -5.6 SDS) and IGFBP-3 (-1.3/2.2 to 
      6.8 SDS) were significantly decreased, but IGFBP-2 (3.2/-0.9 to 8.6 SDS) was
      elevated. Both absolute as well as SDS values of IGF-I, -II and the sum of IGF-I
      and IGF-II (r = -0.49, p < 0.01) were inversely correlated with IGFBP-2. Serum
      levels of the growth factors IGF-I and IGF-II were significantly decreased in
      different types of malignancies to concentrations usually seen only in patients
      with growth hormone deficiency or during starvation. However, the elevated levels
      of IGFBP-2 in 70% of our patients exceeded by far those in growth hormone
      deficiency. Furthermore, in this study we could demonstrate that serum levels of
      IGF-I and IGF-II were inversely correlated to IGFBP-2 independent on the type of
      malignancy, indicating a common regulatory mechanism of the IGF signaling pathway
      in these diseases.

PMID- 7564160
TI  - [Cytogenetic aspects of pediatric germ cell tumors].
AB  - We have performed in situ hybridization (ISH) studies predominantly on paraffin
      sections and on isolated nuclei of 22 pediatric germ cell tumors (GCTs) from 18
      patients including 4 recurrences from three patients. In addition, we performed
      conventional cytogenetic analyses in three tumor samples. Because reports on
      cytogenetic studies in pediatric GCTs are scarce we focused our studies on those
      chromosome abnormalities frequently observed in adult GCTs. These included
      numeric and structural abnormalities of chromosomes 1 and 12 (e.g. isochromosome
      12p) and numeric deviations of chromosomes 8, 10, X and Y. The histological
      subsets of the tumors investigated included two dysgerminomas (DGE), one seminoma
      (SE), one combined seminoma, two embryonal carcinomas (EC), two recurrent ECs,
      six pure yolk sac tumors (YST), five combined teratomas, one immature teratoma
      (IT) and two recurrences of IT, and three differentiated teratomas (TD). Similar
      to the GCTs in adults, additional copies of chromosome 12 were the most
      frequently observed numeric abnormalities. The analysis of two paraffin-embedded
      tumors suggested that changes in the size of the pericentromeric hybridization
      signals of chromosome 12 may be attributed to the presence of i(12)(p10). This
      was confirmed following the karyotype analysis of one EC which unequivocally
      revealed the presence of two i(12)(p10). Interestingly, using these probes, no
      chromosomal abnormalities were found in the pure TD or in the TD cells of mixed
      tumors containing a YST component. In the YST portion, however, the 1p deletions
      and/or numeric chromosome changes were present. Surprisingly, deletions at the
      short arm of chromosome 1, del(1)(p36.3), were frequently observed in malignant
      pediatric GCTs and were the sole abnormality detected in one case.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564162
TI  - Chlamydia pneumoniae infection in children with lower respiratory tract
      infections.
AB  - The incidence of antibody and the clinical features of Chlamydia pneumoniae
      (C.pneumoniae) infection have not been studied in children in Japan. We
      investigated the incidence of C.pneumoniae antibody in sera from 580 healthy
      children (including 30 umbilical cord blood samples) during the 2-year period
      between June 1992 and June 1994. The antibody titer was determined by a
      microimmunofluorescence (MIF) test by using the elementary body of C.pneumoniae
      TW-183 as the antigen. Umbilical cord blood samples were positive for the
      antibody in 50% of newborns tested at birth. The incidence of positivity
      decreased to 0% in 1-year-old children. It was still low in children up to 5
      years of age and then increased rapidly in children 6 years of age or older. The
      positivity reached increased rapidly in children 6 years of age or older. The
      positivity reached 55% in 7-year-old children and remained at this level in
      children older than 7 years of age. High antibody titer (IgG > or = 512),
      indicating recent infection, was observed in 13 (2.2%) of the 580 children, two
      of whom showed no symptoms. We detected the pathogen in throat swabs by culture
      and capillary polymerase chain reaction (PCR), and determined IgM and IgG serum
      titers to C.pneumoniae in 130 children with lower respiratory tract infection (91
      with pneumonia and 39 with bronchitis) between December 1993 and December 1994.
      The infection due to C.pneumoniae was confirmed in 10 (7.7%). Of these, 7 were
      boys and 3 were girls, ranging in age from 9 months to 12 years. The clinical
      manifestations of the infection were mild symptoms like in common cold; post
      nasal discharge, hoarseness and prolonged cough were relatively characteristic.
      There was no significant difference in the incidence of serum positivity between
      the healthy children group and the patients group. The present study suggests
      that primary-schoolers show antibodies for C.pneumoniae with nearly the same
      frequency as adults. Mild clinical symptoms are very common in C.pneumoniae
      infections in children as in adults.

PMID- 7564161
TI  - [Minimal metastatic and minimal residual disease in patients with Ewing tumors].
AB  - At least 95% of Ewing tumors (ET) are characterized by an EWS-gene rearrangement
      with either FLI-1 or ERG and by extraordinary high MIC2/CD99 expression. Both
      features can be used for the specific identification of tumor cells, which might
      also be present in blood and bone marrow in minimal metastatic or minimal
      residual disease. We report the establishment of sensitive ET cell detection
      methods based on these characteristics. Preliminary results of 14 patients are
      given and two cases are reported in detail. 6/14 patients showed RT-PCR
      positivity in the bone marrow whereas in 8/14 patients ET cells could be detected
      by immunofluorescence. Only in 2 patients, one at diagnosis and one at relapse,
      tumor cells were detected in blood samples by RT-PCR. Peripheral blood stem cells
      of 5 patients showed no contamination with ET cells. The versatility of the
      immunocytochemical approach as compared to the RT-PCR analysis is discussed in
      order to explain the discrepancies between the results obtained with the two
      detection methods.

PMID- 7564159
TI  - [Expression and clinical significance of resistance proteins in initial acute
      lymphatic leukemia (ALL) in childhood].
AB  - In a retrospective study the expression of the resistance proteins P-170
      glycoprotein (P-170), glutathione S-transferase pi (GST-pi), thymidylate-synthase
      (TS), dihydrofolate reductase (DHFR) and metallothionein (MT) was investigated in
      111 patients with newly diagnosed acute lymphoblastic leukemia (ALL) using the
      streptavidin-biotin-peroxidase complex method. The expression of the resistance
      proteins was found in following frequency: P-170 in 39 (35%), GST-pi in 54 (49%),
      TS in 46 (42%), DHFR in 21 (20%) and MT in 30 (33%) cases of the investigated
      patients. Patients with overexpression of P-170 or GST-pi had a significant lower
      probability of remaining in continuous first remission (P < 0.05 for P-170 and P
      < 0.01 for GST-pi). The expression of TS and DHFR had no prognostic significance
      on the probability of first remission. Patients with MT-overexpression showed
      only a tendency for a lower probability of continuous first remission.
      Coexpression of P-170 and GST-pi was observed in leukemias of 22 patients (21%)
      and 38 patients (37%) showed no evidence for the expression of both markers.
      Combining P-170 and GST-pi improved the prognostic value. The expression of the
      resistance proteins was independent of age, sex, FAB-type, immunological subtype
      and of the initial peripheral blast cell count. The multivariate analysis
      indicated that only the expression of P-170 was an independent unfavorable
      prognostic factor for children with initial ALL. The reason for this was an minor
      correlation of P-170 and GST-pi (P = 0.01).

PMID- 7564163
TI  - Adult idiopathic chondrolysis of the hip--report of two cases.
AB  - Idiopathic chondrolysis of the hip is characterized by pain, limping and a
      progressive restriction in the range of motion of the hip. The paper describes
      the case of two female patients, age 28 and 37, who were referred to our hospital
      in October 1985 and May 1991 for pain and limitation of movement in the right
      hip. Neither patient had a previous history of systemic illness or trauma or
      medication such as steroids. On admission they underwent clinical and X-ray
      examinations. Both required an open biopsy to confirm the diagnosis. They have
      been followed for 4 years and 8 years, respectively.

PMID- 7564164
TI  - A convenient conversion chart for obtaining serum LDL-cholesterol values.
AB  - I devised a convenient conversion chart to obtain the LDL-cholesterol value from
      the measured total cholesterol, HDL-cholesterol and triglyceride values without
      calculations. The principles and the practical use of the chart are described.
      Its application to the development of slide calculators that allow direct reading
      of LDL-cholesterol value is also discussed.

PMID- 7564165
TI  - Inhibition of Fc gamma R- and CR-mediated human neutrophil chemiluminescent
      responses by anti-allergic and anti-histaminergic drugs.
AB  - The effects of ketotifen fumarate (KF) and clemastine fumarate (CF) on neutrophil
      chemiluminescent (CL) responses to zymosan particles coated with either IgG
      (IgGZ), C3 (C3Z), or both (IC3Z), were examined in vitro. These opsonized
      zymosans caused not only detectable neutrophil superoxide anion generation
      evaluated by an MCLA-dependent CL (MDCL) assay, with the order of light emission
      being IC3Z > IgGZ > C3Z, but also a transient rise of neutrophil [Ca2+]i measured
      by an aequorin-dependent CL (ADCL) assay. Both KF and CF could suppress all
      opsonized zymosan-induced neutrophil MDCL in a dose-dependent fashion, but not
      all ADCL. Similar inhibitory effects of KF and CF were observed on the phorbol
      myristate acetate-induced MDCL. However, there was no interference by these two
      drugs with the measurement of MDCL in the hypoxanthine/xanthine oxidase
      superoxide anion generation system. These results indicate that the inhibitory
      effects of both KF and CF on Fc gamma R- and/or CR-mediated neutrophil oxidative
      potential is attributable to effects on an enzymatic reaction after protein
      kinase C activation in the oxidative signal transduction pathway.

PMID- 7564166
TI  - Clinicopathologic characteristics of stage I lung adenocarcinoma in women.
AB  - A total of 75 cases of surgically resected Stage I lung adenocarcinoma in women
      were analyzed. The patients were divided into three age groups: less than 50,
      between 50 and 70, and more than 70 years old. On the basis of the pathological T
      factor, 45 of 75 (60%) were T1 and 30 of 75 (40%) were T2 tumor. On the basis of
      pleural involvement, 47 of 75 (63%) cases revealed p0. On the basis of
      differentiation, all but two cases (97%) were well to moderately differentiated.
      On the basis of structure, papillary adenocarcinoma were 64 of 75 (85%). There
      was no difference among the three age groups in the pathological findings.
      Survival curves of each group indicated no statistically significant difference.
      We suggest that hormonal factors related to age do not affect the characteristics
      of lung cancer in women nor the survival of the patients.

PMID- 7564167
TI  - Plasma concentrations of atrial natriuretic peptide in cardioembolic stroke with
      atrial fibrillation.
AB  - The aim of the present study was to determine whether the level of plasma atrial
      natriuretic peptide (ANP), an indicator of atrial stretching, correlates with the
      formation of a thrombus in the left atrium during cardioembolic stroke with
      atrial fibrillation. Plasma concentrations of immunoreactive ANP and thrombin
      antithrombin III complex (TAT) were measured in five age-matched groups
      including: 16 patients with acute cardioembolic stroke and atrial fibrillation
      (group 1), 26 patients with chronic cardioembolic stroke and atrial fibrillation
      (group 2), 27 patients with atrial fibrillation without previous stroke (group
      3), 21 patients with acute lacunar stroke (group 4), and 27 healthy controls. The
      plasma ANP levels were higher in group 1, regardless of the stage, than those
      estimated at chronic stage in group 4 and in healthy controls. There were no
      stage-related differences between groups 1, 2 and 3. Plasma levels of ANP in
      group 2, a high risk group of cardioembolic stroke, were higher than in group 3,
      a low risk group. There was no correlation between plasma levels of ANP and mean
      blood pressure, pulse rate or plasma levels of TAT in any group. These results
      indicate that the determination of plasma ANP concentration is useful to
      distinguish a high risk patient from a low risk patient and also a cardioembolic
      stroke patient from a lacunar stroke patient. They also underscore the
      difficulties in recognizing left atrial thrombus formation by determining the
      plasma ANP concentration in cardioembolic stroke.

PMID- 7564168
TI  - Developmental pattern of urinary ketonic bile acids during the neonatal period.
AB  - We tested the hypothesis that healthy neonates and infants excrete in the urine
      ketonic bile acids, delta 4-3-oxo bile acids and delta 1-3-oxo bile acids. The
      hypothesis is based on the finding of ketonic bile acids in amniotic fluid at
      full term. We measured the urinary concentration of ketonic bile acids during the
      neonatal period. Urine from 24 healthy full-term infants (aged 3 d and 1, 2, and
      3 mo, six per group) was analyzed for bile acids by gas chromatography-mass
      spectrometry with selected ion monitoring. Large amounts of ketonic bile acids
      were detected in the urine of healthy neonates and infants. The concentration of
      ketonic bile acids in urine at age 3 d was significantly higher than at age 1, 2,
      or 3 mo (P < 0.01, P < 0.01, P < 0.001, respectively). This study demonstrates
      that healthy new-born infants excrete large amounts of ketonic bile acids in the
      urine.

PMID- 7564169
TI  - Resected early gastric cancer--clinicopathological studies on 610 cases.
AB  - A total of 610 cases of early gastric cancer were studied, retrospectively. Of
      these, 541 (88.7%) cases were single and 62 (10.1%) cases were multiple cancers.
      Lymph node metastasis occurred in 11.2% of the elevated, in 8.2% of the depressed
      and in 15.1% of the mixed type. There was no lymph node metastasis when a mucosal
      or submucosal cancer was less than 10 mm in diameter. By contrast, in the cases
      in which the preoperative diagnosis was suspected advanced cancer, the incidence
      of lymph node metastasis was high, at 33%. Therefore, when the preoperative
      diagnosis is advanced cancer, standard radical gastrectomy and/or extended
      radical gastrectomy should be selected even though they are found to be early
      gastric cancer. The age-corrected 5-year survival rate was 98.5% in the cases
      with no lymph node metastasis and 93.0% in the cases with lymph node metastasis
      (p > 0.05). The 5-year survival rate was 100% in mucosal cancer and 95.5% in
      submucosal cancer (p > 0.05).

PMID- 7564171
TI  - [Defeat to violence. "Everybody is responsible to everyone about everything"].

PMID- 7564172
TI  - [Basal stimulation. Reviving through the senses].

PMID- 7564170
TI  - Relationships between eosinophil-associated parameters and disease severity in
      atopic dermatitis.
AB  - This study demonstrated not only the presence of house dust mite antigen (HDM)
      specific IgE and IgG antibodies in the sera of 27 patients with atopic dermatitis
      (AD), but also considerably increased levels of serum eosinophil cationic protein
      (ECP) and uniformly nadir levels of plasma ECP, which provides evidence for ECP
      release from eosinophils in vitro. Besides blood eosinophilia, AD patients had an
      increased number of CD32+ eosinophils and EG2+ "activated" eosinophils; both of
      which, especially the latter, were significantly correlated with elevated levels
      of serum ECP. AD-source eosinophils had enhanced sensitivity for IgG-immune
      complexes corresponding to their increased expression of CD32, whereas neither
      HDM alone nor IgE/HDM-immune complex induced eosinophil activation. There were no
      gamma globulin-bearing cells in AD-source eosinophils, indicating that serum ECP
      levels may be dependent on EG2+ eosinophil numbers rather than the state of CD32
      mediated eosinophil degranulation, as shown in vitro. Since HDM can cause an
      eczematous skin reaction accompanying the eosinophil accumulation and
      degranulation in sensitized AD, increased numbers of both CD32+ and EG2+
      eosinophils according to the extent of AD severity indicates that these
      eosinophil in vivo generations and their subsequent functioning in the lesional
      skin may be regulated through HDM-initiated dermatitis events, and then, may form
      a vicious circle as the AD lesions spread.

PMID- 7564173
TI  - ["Here I am regarded as a person ...". Interview by Claire Cuendet].

PMID- 7564174
TI  - [Decisions for the future].

PMID- 7564175
TI  - [Depression. III. Building a relationship. Listening, bearing, accompanying].

PMID- 7564176
TI  - [An excursion on the historical and social change of a term. Autonomy and the
      illusion of freedom].

PMID- 7564177
TI  - [Violence must not be a taboo].

PMID- 7564178
TI  - [Towards better attention while accompanying patients to the end of their lives.
      Harmonic song].

PMID- 7564179
TI  - [Transparently and with exact information...].

PMID- 7564180
TI  - [Does the self-care concept work at home? Support for self-care].

PMID- 7564181
TI  - [Preparations for a project. Personal care also in home care].

PMID- 7564182
TI  - ["I bring her food and heat her home"].

PMID- 7564183
TI  - [A questionable letter].

PMID- 7564184
TI  - [The nurses without borders tell: the heart overflows with memories].

PMID- 7564185
TI  - [The unfortunate auto-dynamics of institutions].

PMID- 7564186
TI  - [Working in zones of armed conflict. The difficulty of learning humility].

PMID- 7564187
TI  - [Directly from Bosnia: facing the absurdity of war: engagement and powerlessness
      of nurses].

PMID- 7564188
TI  - [The struggle for quality and efficiency].

PMID- 7564190
TI  - [The Bethel Foundation. A head full of projects].

PMID- 7564189
TI  - [Impact of stress on the psychological equilibrium. Living through the return].

PMID- 7564191
TI  - [Empathy as an antidote to violence].

PMID- 7564192
TI  - [Dependent elderly. Helpful measures].

PMID- 7564193
TI  - [Successful attempt to overcome the fear and insecurity in the presence of
      patients with AIDS. How I turned into a trusted companion].

PMID- 7564195
TI  - [Mouth and eye care].

PMID- 7564196
TI  - [Exercise therapy for cardiac insufficiency].

PMID- 7564194
TI  - [Health structure legislation--a chance for nursing services?].

PMID- 7564197
TI  - [Clinical significance of breast sonography].

PMID- 7564199
TI  - [Touch is essential to everybody].

PMID- 7564200
TI  - [A new generation of protective wound cremes. New: a protective wound creme for
      babies by PENATEN].

PMID- 7564198
TI  - [Fistulas in the upper gastrointestinal tract, combined with a defect in the
      abdominal wall--a standardized therapeutic concept].

PMID- 7564201
TI  - [Vitamin-rich nutrition is no alibi for unhealthy habits].

PMID- 7564202
TI  - [There is only effective or ineffective medicine].

PMID- 7564203
TI  - [On the joys of duty].

PMID- 7564204
TI  - Provision for welfare of non-human primates used in biomedical research.

PMID- 7564205
TI  - Biological propensities of the Callitrichinae: a much used-little known group.
AB  - The use of callitrichid primates in biomedical research was encouraged initially
      by their susceptibility to various diseases such as infectious hepatitis and
      rubella. However, there was no supporting biological knowledge which helped to
      keep them healthy and breed effectively in captivity. Further, various
      callitrichid biomedical models are endangered species; hence, animal welfare and
      primate conservation are interrelated. Recent information has extended our
      knowledge of the natural life styles of these species in various ways; but there
      is still little to predict persistent concerns of effective management in
      captivity. Hence, we need practical information such as those derived from
      laboratory records of housing, reproduction, diet and health, together with
      studies that compare specifically behaviour in different laboratory conditions.
      More important in the long run, is that we study the biobehavioural propensities
      of different species. As yet callitrichids are largely unknown in these regards-
      a situation that continues to present problems for the reliability, validity,
      standardization and generalization of experimental procedures.

PMID- 7564206
TI  - Guidelines and legal codes for the welfare of non-human primates in biomedical
      research.
AB  - Recommendations have been drawn up in different countries for the housing of non
      human primates. Four of them are compared and it is clear that there is little
      consistency with regard to spatial allowances or suitable temperature and
      humidity ranges. Often the cage sizes quoted are incompatible with requirements
      to meet the behavioural needs of the animals. Only one provides guidance on
      primates' different social needs. To achieve greater consistency and credibility,
      guidelines should be regularly revised to include advances in our knowledge of
      the animals' needs.

PMID- 7564207
TI  - Individual differences in macaques' responses to stressors based on social and
      physiological factors: implications for primate welfare and research outcomes.
AB  - Primates are used extensively in a variety of research settings. Federal
      regulations in the US mandate that caretakers provide for the 'psychological well
      being of laboratory primates'. One of the difficulties in implementing this law
      has been both in the definition of psychological well-being and in the need to
      deal with each primate species and, in some cases, age or sex class, uniquely.
      Non-human primates exhibit distinct individual differences in their behavioural
      and physiological responses to experimental challenges and caretaking procedures.
      We have been investigating what factors can predict some of these individual
      differences, and have found that factors both intrinsic and extrinsic are
      significant. Extrinsic factors found to predict individual differences in
      response to stressors include the nature and prior experience with the challenge,
      the presence of familiar peers and availability of social support. Intrinsic
      factors include cognitive interpretations of the challenge and temperamental
      differences in reactivity. These studies highlight the importance of
      understanding the context and individual psychology of macaques in order to
      provide laboratory environments conducive to their welfare, and in order to
      understand the impact experimental and caretaking procedures are likely to have
      on the health and welfare of our subjects.

PMID- 7564208
TI  - Measurement of blood pressure and heart rate by telemetry in conscious
      unrestrained marmosets.
AB  - A system is described for the continuous measurement of blood pressure, heart
      rate and motor activity by telemetry in conscious marmosets freely moving in
      their home cages. Consistent diurnal variations in these parameters were observed
      under standard conditions. However these parameters were sensitive to changes in
      the environment. Blood pressure values were similar to those measured by non
      telemetric methods in conscious restrained marmosets while heart rate values were
      significantly lower.

PMID- 7564209
TI  - Carbon dioxide euthanasia in rats: oxygen supplementation minimizes signs of
      agitation and asphyxia.
AB  - This paper records the effects of carbon dioxide when used for euthanasia, on
      behaviour, electrical brain activity and heart rate in rats. Four different
      methods were used. Animals were placed in a box (a) that was completely filled
      with carbon dioxide; (b) into which carbon dioxide was streamed at a high flow
      rate; (c) into which carbon dioxide was streamed at a low flow rate and (d) into
      which a mixture of carbon dioxide and oxygen was streamed at a fast rate. It was
      found that the cessation of behaviour was associated with an aberrant pattern of
      electrical brain activity together with an abnormally low heart rate. The time to
      reach this point was shortest in those animals placed in the box filled with pure
      carbon dioxide, longer when carbon dioxide was introduced at a high rate into the
      box, longer still when oxygen was added to the carbon dioxide gas, and longest
      when carbon dioxide was streamed slowly into the box. In the condition with pure
      carbon dioxide, signs of behavioural agitation and asphyxia were seen. This was
      also true for the two conditions in which carbon dioxide streamed into the box,
      but to a lesser degree. These signs occurred when some degree of consciousness
      may still have been present in the animals. Signs of agitation and asphyxia were
      almost completely absent in the condition where oxygen was added to the carbon
      dioxide. These results not only demonstrate the usefulness of behavioural
      criteria next to electrophysiological indices, but also demonstrate that the
      negative effects of carbon dioxide euthanasia can be prevented by an additional
      supply of oxygen.

PMID- 7564210
TI  - Evaluation of thiopentone-midazolam-fentanyl anaesthesia in pigs.
AB  - Induction of anaesthesia in swine by thiopentone (27.1-35.7 mg/kg, mean 29.9
      mg/kg) was followed by bolus doses and continuous infusion of midazolam and
      fentanyl (0.90 mg/kg followed by 0.90 mg/kg/h and 0.025 mg/kg followed by 0.025
      mg/kg/h, respectively). This produced good anaesthesia and analgesia for up to 2
      h in 6 Norwegian Landrace pigs (wt: 17-42 kg), based on responses to painful
      stimuli elicited by pinching the nasal septum, the mouth, the forefoot and the
      perineal skin area. The first responses occurred after 110 min of anaesthesia. No
      significant drop in rectal temperature due to the regimen was noted during
      monitoring periods (140-180 min). This combined intravenous anaesthetic regimen
      gave good anaesthesia and analgesia to pigs for up to 2 h as monitored by
      clinical signs. The regimen may not be sufficient for longer time periods. We
      cannot advocate the incorporation of neuromuscular blocking agents in this
      regimen.

PMID- 7564211
TI  - The topography, structure and incidence of mineralized bodies in the basal
      ganglia of the brain of cynomolgus monkeys (Macaca fascicularis).
AB  - Whole coronal slices from 6 levels of the brain of 16 cynomolgus monkeys (8
      control and 8 treated by daily gavage with a novel pharmaceutical agent for one
      year) were examined histologically. Mineralized bodies were identified only in
      coronal sections passing through the optic chiasma and mammillary bodies.
      Identical mineralized structures were present in the basal ganglia of both
      control and treated animals. The majority were seen in the globus pallidus,
      occasionally in the putamen and once in the nearby caudate nucleus. These
      structures were partially ferruginated and also partially calcified. They
      appeared to arise in relation to small vessels. They are part of the naturally
      occurring background pathology of several species of non-human primates and the
      incidence in this study (3/8 control and 5/8 treated) was approximately what
      might be expected from reports in the literature. Mineralized bodies of the basal
      ganglia of primates represent a spontaneous lesion with a characteristic
      distribution. They may cause confusion in interpretation of toxicological studies
      if their natural occurrence is not appreciated.

PMID- 7564212
TI  - A transport and monitoring unit for piglets under general anaesthesia.
AB  - A transport and monitoring unit for fully anaesthetized piglets (weight 20-30 kg)
      was made. The unit provided easy transport for short or longer distances while at
      the same time making continuous monitoring of invasive blood pressure (IBP),
      temperature and HR possible. The animals stayed in the unit for the duration of
      the experiments which required that the anaesthetized animal be kept in exactly
      the same position for several hours. This, as well as the experimental animal's
      welfare, was ensured by the unit. Such a unit can be used for any lengthy
      transportation of experimental animals to research facilities located separately
      from animal laboratories.

PMID- 7564213
TI  - Change in locomotor activity pattern in mice: a model for recognition of
      distress?
AB  - Recognition and assessment of pain and distress is made by observing common
      clinical and behavioural signs. Observation usually occurs during a limited
      period of time and results can be biased by interpretation of an individual
      observer. To improve objective assessment of distress we studied the locomotor
      activity pattern of mice during a 24-h interval. As a reference compound,
      Freund's complete adjuvant (FCA) was used. Mice were injected intraperitoneally
      with different doses FCA (0, 0.1, 0.2 and 0.5 ml) and observed for 5 to 7 days.
      Animals did not appear to be in pain and seemed to have a normal activity and
      behaviour pattern at first sight, however FCA induced a dose-dependent decrease
      of body weight. Open field activity (total distance run) measured during a
      limited period of time was not altered as a result of FCA. However, nocturnal
      activity was dose dependently decreased during the first 3 to 4 nights after
      treatment with FCA. The data presented indicate that using locomotor activity
      patterns over 24 h might be a useful adjunct and an objective approach to assess
      distress.

PMID- 7564214
TI  - Serological studies of Corynebacterium kutscheri and coryneform bacteria using an
      enzyme-linked immunosorbent assay (ELISA).
AB  - An enzyme-linked immunosorbent assay (ELISA) to measure Corynebacterium kutscheri
      antibodies in mice and rats was developed. Seven C. kutscheri isolates showed
      considerable serological relationship, but Japanese isolates differed from the
      British isolates. The ELISA appeared specific since C. kutscheri antigen did not
      react with antisera against 8 heterologous coryneform species. Antibodies to C.
      kutscheri were to a limited extent absorbed by autologous and homologous antigen,
      but not at all by the heterologous coryneform species. In naturally infected wild
      Rattus norvegicus and laboratory NA rats, the ELISA demonstrated high ODs to C.
      kutscheri.

PMID- 7564215
TI  - Leptospira interrogans serovar sejroe infection in a group of laboratory dogs.
AB  - Interstitial nephritis was seen histologically in 19 (59%) out of 32 pure-breed
      beagle dogs (16 males and 16 females) subjected to standard safety tests. In
      these animals no clinical abnormalities were observed and all the tested
      parameters (haematology, biochemistry and urine analysis) were within the normal
      ranges. Leptospiral antibody titres ranging from 1 : 100 to 1 : 6400, against a
      serovar (hardjo) belonging to the Sejroe serogroup, were detected by the
      microscopic agglutination test (MAT) in the serum of the 19 dogs with
      interstitial nephritis. All animals without renal lesions were seronegative.
      Leptospiral antigen was detected immunohistochemically in the kidneys of 4 dogs;
      leptospires were detected in Warthin-Starry stained sections of one dog.
      Leptospires were isolated from the kidneys of 3 of the 4 dogs examined by
      bacterial culture. The isolated strains were typed as serovar sejroe by
      restriction endonuclease digestion and Southern blot hybridization analysis of
      their DNA. It was concluded that Leptospira interrogans serovar sejroe, was
      responsible for an asymptomatic chronic renal infection which was widespread in
      this group of laboratory dogs.

PMID- 7564216
TI  - An enzyme-linked immunosorbent assay (ELISA) for monitoring rodent colonies for
      Pasteurella pneumotropica antibodies.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of
      Pasteurella pneumotropica antibodies in the sera of rats, mice, hamsters and
      Mastomys. P. pneumotropica from mice and rats showed cross-reactivity. The ELISA
      using P. pneumotropica NCTC 8284 detected more infected animals than selective
      culture in groups of rodents from which P. pneumotropica, Haemophilus sp and/or
      Actinobacillus sp were cultured. Cross reactivity between P. pneumotropica NCTC
      8284 and haemophilus and actinobacillus isolates were not studied.

PMID- 7564217
TI  - Reclassification of 30 Pasteurellaceae strains isolated from rodents.
AB  - Thirty Pasteurellaceae strains isolated from gerbil, guineapig, hamster, mouse,
      muskrat and rat were reinvestigated and reclassified after comparison with
      reference strains. Strains originally described as Pasteurella pneumotropica were
      reclassified as [Pasteurella] pneumotropica Heyl biotype (7), [P.] pneumotropica
      Jawetz biotype (1), Pasteurella dagmatis (1) or Taxon 22 (2). Strains previously
      reported as Actinobacillus sp. were reclassified as [P.] pneumotropica biotype
      Jawetz (3), P. dagmatis (3) or Taxon 6 (7). Strains earlier described as
      Pasteurella gallinarum were renamed as SP group pasteurella (4) or Taxon 25 (2).
      Some of these reclassified Pasteurellaceae have not been reported previously in
      rodents. The present findings underline the importance of extended
      characterization of isolates and comparison with references strains to avoid
      misclassification within the family Pasteurellaceae Pohl 1981.

PMID- 7564218
TI  - Potential of two-cell mouse embryos to develop to term despite partial damage
      after cryopreservation.
AB  - Approximately 18% of cryopreserved 2-cell mouse embryos of 26 different batches
      showed various degrees of morphological damage after the freeze-thaw process.
      Normal and damaged morphology were assessed by light microscopy and the ability
      of an embryo to develop in vitro to a blastocyst, or to develop to term, after
      transfer to foster mothers. Using vital stains such as Fluorescein-diacetate
      (FDA) and 4', 6-Diamidino-2-Phenylindole (DAPI) it was found that in
      approximately 82% of the cases, both of the 2 blastomeres of the cryopreserved
      embryos survived the freeze-thaw process; in 10% only one cell survived the
      process; and in 8% none survived. Normally, only intact 2-cell embryos are
      considered for transfer. Here it was shown that over 60% of the partially damaged
      embryos developed in vitro to the blastocyst stage and, of those, 26% developed
      to term after transfer to suitable foster mothers. Although the inner cell mass
      (ICM) appeared to remain smaller during culture after the transfer of partially
      damaged 2-cell stage embryos, no difference during gestation period was found
      compared with intact embryos.

PMID- 7564219
TI  - Influence of prostaglandins E2 and F2 alpha on passage pressure across the
      uterotubal junction and isthmus in the rat.
AB  - The influence of prostaglandins E2 and F2 alpha on passage pressure across the
      uterotubal junction (UTJ) and isthmus were studied in rats that were either in
      the pro-oestrus, oestrus, metoestrus or dioestrus phases. Effects of these
      prostaglandins were also investigated in rats that had been either ovariectomized
      and treated with oestradiol or medroxiprogesterone acetate, or only
      ovariectomized. In each rat, the left UTJ was surgically resected and the isthmus
      anastomosed to the uterine horn, whereas the right UTJ was left untouched. The
      passage pressures across the left isthmus and the right UTJ were measured before
      and after prostaglandin treatment. The pressures obtained in the UTJ in the
      oestrus phase and oestrogen-treated ovariectomized animals were lower than those
      registered in the remaining groups. Prostaglandin E2 decreased the pressures when
      compared with pre-treatment measures in all groups. Significantly higher
      pressures were registered across the UTJ in prostaglandin F2 alpha than in E2
      treatment, with these higher pressures being similar to pre-treatment pressures.
      Both hormonal changes throughout the oestrous cycle and prostaglandin E2
      treatment had a similar influence on the passage pressure across the isthmus, as
      that described for UTJ, but with lower values. The results indicate that
      prostaglandin E2 decreases the passage pressure across both UTJ and isthmus and
      can have an influence on the regulation of transport across these 2 areas.

PMID- 7564220
TI  - Ovarian changes in Sprague-Dawley rats produced by nocturnal exposure to low
      intensity light.
AB  - This study was performed to investigate the potential effects of nocturnal, low
      intensity light upon ovarian morphology of female Sprague-Dawley rats and to
      investigate the cause for ovarian changes which had been observed in an earlier
      study following transient exposure of control female Sprague-Dawley rats to
      indirect light of minimal intensity during the nocturnal 12-h dark cycle. Twenty
      female Sprague-Dawley CD rats (initial age: 5 weeks) were kept for 8 weeks under
      our standard laboratory conditions including a daily 12-h light cycle (light
      intensity: approximately 200 lux) followed by a 12-h dark cycle with exposure to
      an indirect light source of low intensity (approximately 30 lux). Ten female
      control rats of comparable age from a concurrent toxicology study housed in an
      adjacent animal room under our standard 12 h light/dark cycle served as controls.
      At the end of the study the rats were sacrificed, necropsied and the ovaries were
      evaluated histopathologically. In 5 of the 20 animals we found ovarian atrophy
      consisting of decreased number and size of corpora lutea and increased number of
      tertiary follicles and/or follicular cysts. Most corpora lutea present in these
      ovaries were old, indicating the absence of recent ovulations. In contrast, the
      incidence of ovarian changes in the control group was 0/10. In conclusion,
      nocturnal exposure of female Sprague-Dawley rats to light of minimal intensity
      produced a substantial incidence of ovarian changes and suggests that the
      incidence of ovarian atrophy observed in a previous study may have been due to
      transient exposure to indirect nocturnal light of minimal intensity.

PMID- 7564221
TI  - Microchip implant system used for animal identification in laboratory rabbits,
      guineapigs, woodchucks and in amphibians.
AB  - Traditional methods for animal identification have a number of drawbacks. We
      evaluated a new system for individual identification using microchip implants in
      rabbits, guineapigs, woodchucks (Marmota monax) and amphibians (Xenopus laevis,
      Pleurodeles waltlii). Implantation procedure and long-term observations are
      described. Microchip implants proved to be a practicable and reliable system for
      animal identification without obvious adverse effects. The applicability of
      electronic animal identification in comparison with common methods and with
      regard to animal welfare and legal aspects is discussed.

PMID- 7564222
TI  - Tyrosinaemia type I: considerations of treatment strategy and experiences with
      risk assessment, diet and transplantation.

PMID- 7564223
TI  - Liver transplantation in tyrosinaemia type I: the Groningen experience.

PMID- 7564224
TI  - Liver transplantation in nine Spanish patients with tyrosinaemia type I.

PMID- 7564226
TI  - Nutritional value of essential amino acids in the treatment of adults with
      phenylketonuria.

PMID- 7564225
TI  - Plasma antioxidant capacity in two cases of tyrosinaemia type 1: one case treated
      with NTBC.

PMID- 7564227
TI  - Improvements in behaviour and physical manifestations in previously untreated
      adults with phenylketonuria using a phenylalanine-restricted diet: a national
      survey.

PMID- 7564228
TI  - Physical growth in patients with phenylketonuria.

PMID- 7564229
TI  - Long-term follow-up of 77 patients with isolated methylmalonic acidaemia.

PMID- 7564230
TI  - Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase
      deficiency.

PMID- 7564231
TI  - Biochemical follow-up in late-treated nephropathic cystinosis.

PMID- 7564232
TI  - Galactosaemia: relationship of IQ to biochemical control and genotype.

PMID- 7564233
TI  - Catch-up growth in Fanconi-Bickel syndrome with uncooked cornstarch.

PMID- 7564234
TI  - Case report: four-year follow-up of bone-marrow transplantation in late juvenile
      metachromatic leukodystrophy.

PMID- 7564235
TI  - Juvenile metachromatic leukodystrophy: neurological outcome two years after bone
      marrow transplantation.

PMID- 7564237
TI  - Immunosuppressive effects of organic acids accumulating in patients with maple
      syrup urine disease.

PMID- 7564236
TI  - Defective neutrophil activity in fructose-1,6-diphosphatase deficiency.

PMID- 7564238
TI  - Acute pancreatitis in propionic acidaemia.

PMID- 7564239
TI  - Early signs and course of disease of glutaryl-CoA dehydrogenase deficiency.

PMID- 7564240
TI  - Folinic acid responsive seizures: a new syndrome?

PMID- 7564241
TI  - Diagnosis of a new case of trimethylaminuria using direct proton NMR spectroscopy
      of urine.

PMID- 7564242
TI  - Combined deficiencies of NADPH- and NADH-dependent dihydropyrimidine
      dehydrogenases, a new finding in a family with thymine-uraciluria.

PMID- 7564243
TI  - Organic acids in cerebrospinal fluid and plasma of patients with L-2
      hydroxyglutaric aciduria.

PMID- 7564244
TI  - D-2-hydroxyglutaric acidaemia: identification of a new enzyme, D-2
      hydroxyglutarate dehydrogenase, localized in mitochondria.

PMID- 7564245
TI  - Segregation of the N301T mutation in the family of the index patient with
      mevalonate kinase deficiency.

PMID- 7564246
TI  - Phytanic acid oxidation in man: identification of a new enzyme catalysing the
      formation of 2-ketophytanic acid from 2-hydroxyphytanic acid and its deficiency
      in the Zellweger syndrome.

PMID- 7564247
TI  - 3-hydroxyisobutyric aciduria with a mild clinical course.

PMID- 7564248
TI  - RFLPs for linkage analysis in families with glycogen storage disease type III.

PMID- 7564249
TI  - Molecular analysis of patients affected by homocystinuria due to cystathionine
      beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in
      intron 11.

PMID- 7564250
TI  - Prenatal diagnosis for Canavan disease: the use of DNA markers.

PMID- 7564251
TI  - DIDMOAD syndrome; further studies and muscle biochemistry.

PMID- 7564252
TI  - Mitochondrial complex deficiencies in a male with cardiomyopathy and 3
      methylglutaconic aciduria.

PMID- 7564253
TI  - KBS-DIAMET: database and expert system for diagnosis and treatment of patients
      with inborn errors of metabolism.

PMID- 7564254
TI  - Riboflavin-responsive epilepsy in a patient with SER209 variant form of short
      chain acyl-CoA dehydrogenase.

PMID- 7564255
TI  - A patient with lethal cardiomyopathy and a carnitine-acylcarnitine translocase
      deficiency.

PMID- 7564256
TI  - Six years' experience with carnitine supplementation in a patient with an
      inherited defective carnitine transport system.

PMID- 7564257
TI  - Clinical and biochemical findings in a Spanish boy with primary carnitine
      deficiency.

PMID- 7564258
TI  - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: high frequency of the
      G1528C mutation with no apparent correlation with the clinical phenotype.

PMID- 7564260
TI  - Mitochondropathy presenting with non-ketotic hypoglycaemia as 3
      hydroxydicarboxylic aciduria.

PMID- 7564261
TI  - Is genotyping useful for the screening of medium-chain acyl-CoA dehydrogenase
      deficiency in France?

PMID- 7564259
TI  - Clinical and biochemical presentation of long-chain 3-hydroxyacyl-CoA
      dehydrogenase deficiency.

PMID- 7564262
TI  - Do criteria exist from urinary organic acids to distinguish beta-oxidation
      defects?

PMID- 7564263
TI  - Rheumatoid arthritis. The multiple pathways to chronic synovitis.

PMID- 7564264
TI  - Insulin-like growth factor-I receptor. Its role in cell proliferation, apoptosis,
      and tumorigenicity.
AB  - From the point of view of cell growth, the IGF-IR activated by its ligands has
      three important functions: (a) it is required for optimal growth both in vivo and
      in vitro, although some growth occurs even in its absence; (b) it is obligatory
      for the establishment and maintenance of the transformed phenotype and for
      tumorigenesis for several types of cells; and (c) it protects cells from
      apoptosis, both in vivo and in vitro. The IGF-I receptor does seem to occupy a
      central role in these processes. Whereas an overexpressed IGF-I receptor is
      mitogenic for IGF-I alone and is fully transforming and protects cells from
      apoptosis, the same cannot be said for overexpressed EGF and PDGF receptors (205,
      206). These two receptors can neither induce growth or transform most cells
      lacking IGF-I receptors. The reversal of the transformed phenotype and the
      induction of apoptosis that occur when the levels of IGF-I receptors are
      artificially decreased also point out the essential role of the receptor in these
      three processes. An important distinction in this regard is that it is not so
      much an overexpressed IGF-I receptor that is important in transformation but the
      lack of it that does not allow the transformed phenotype. This distinction is
      extremely important if we wish to use the IGF-IR as an approach to therapeutic
      interventions. Returning to more basic questions, a mutational analysis of the
      IGF-I receptor has shown that specific domains are involved in its mitogenicity
      or its ability to facilitate transformation and that these two processes can be
      separated at the level of the receptor itself. This finding raises a crucial
      question: Is the transforming activity using a pathway that is separate from the
      mitogenic signaling pathway? Alternatively, is it simply a question of a
      quantitative effect? The answer to this question could be a very important
      contribution to the mechanism of transformation. Little is known about the
      mechanism(s) by which the IGF-I receptor protects cells from apoptosis; here
      again, some fundamental questions can be raised. Are there specific domains in
      the receptor for its antiapoptotic activity? Is this activity tied to mitogenesis
      and/or transformation? Which elements in the signal transduction pathway are
      involved in these three different functions of the IGF-I receptor? Although many
      problems are still unresolved, the last few years have seen a very rapid rise in
      the importance of the IGF-I receptor in both normal and abnormal growth.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7564265
TI  - Expression of CD60 on multiple cell lineages in inflammatory synovitis.
AB  - BACKGROUND: CD60 is a recently described T cell subset marker that is expressed
      on the surface of most T lymphocytes in synovial tissue and fluid and on a
      smaller proportion of peripheral T cells. Activation of T lymphocytes can be
      triggered through CD60. CD60 is also expressed by neuroectodermally derived cells
      in thymic epithelium and in skin. EXPERIMENTAL DESIGN: Immunohistologic analysis
      of CD60 expression in synovium and thymus was performed using formalin-fixed
      tissue samples. Nonlymphoid cell lines grown from similar tissues were analyzed
      by flow cytometry. RESULTS: CD60 was readily identified in formalin-fixed,
      paraffin-embedded tissues. Simultaneous examination of CD60 distribution and cell
      morphology demonstrated that, in addition to its presence on T cells, CD60 was
      also expressed by a variety of nonlymphoid cells in synovium, including synovial
      lining cells, vascular endothelium, and dendritic-appearing cells deep within
      synovial tissue. Synovial tissue expression of CD60 was similar in rheumatoid
      arthritis and in other forms of inflammatory arthritis. In addition, it was
      strongly expressed by giant cells in pigmented villonodular synovitis. Surface
      expression of CD60 was detected by flow cytometry on cultured synoviocytes and on
      other CD60+ nonlymphoid cells, thus excluding adsorption of CD60 shed by T cells
      as a sufficient explanation of the immunohistologic findings. CONCLUSIONS: These
      results define the T cell-activating CD60 determinant as a broadly distributed Ag
      within synovial tissue, with a possible functional role in the activation of a
      variety of cellular populations. CD60 may also be a marker for previously
      undescribed cell subsets in the synovial compartment, possibly including a cell
      population of neuroectodermal origin.

PMID- 7564266
TI  - Expression of basic fibroblast growth factor in synovial tissue from patients
      with rheumatoid arthritis and degenerative joint disease.
AB  - BACKGROUND: Recent studies have implicated polypeptide growth factors in the
      development of rheumatoid arthritis (RA), which is characterized by synoviocyte
      hyperplasia and neovascularization. One such polypeptide, basic fibroblast growth
      factor (bFGF), is of particular interest because of its potent mitogenic and
      angiogenic activities. We have previously reported that cultured human
      synoviocytes synthesize and bind bFGF and also proliferate in response to it (1).
      Recently, we found a close association between increased bFGF expression and
      destructive changes in arthritic joints from rats (2). Now we extend our study by
      detecting in vivo expression of bFGF in human synovial tissues obtained from
      patients with RA. EXPERIMENTAL DESIGN: Human synovial tissues from patients with
      RA, degenerative joint disease (DJD), and trauma were collected during joint
      surgery. The expression of bFGF protein and mRNA by the synovia was examined by
      immunolocalization, Western blot, Northern blot, and RNase protection assays.
      Synovium from patients with DJD and trauma was used to compare with rheumatoid
      synovium. Double immunostaining with cell type-specific antibodies was carried
      out to identify cellular sources of bFGF. RESULTS: Both polypeptide and mRNA for
      bFGF were detected in the synovial samples examined. Increased bFGF staining was
      found in synovium-cartilage interface where joint destruction occurred and in
      hyperplastic synoviocytes of a subset of rheumatoid synovium. Strong cytoplasmic
      bFGF staining was localized in the majority of mast cells and vascular cells.
      CONCLUSIONS: Synovial tissue from patients with RA, DJD, and trauma express bFGF.
      Increased bFGF staining in the hyperplastic lining synoviocytes and at the pannus
      cartilage interface suggests that bFGF may play a role in synovial hyperplasia
      and joint destruction. Strong cytoplasmic bFGF staining found in mast cells and
      vascular cells indicates that these cells are the major sources of tissue bFGF.

PMID- 7564267
TI  - Human synovial fibroblasts coexpress IL-1 receptor type I and type II mRNA. The
      increased level of the IL-1 receptor in osteoarthritic cells is related to an
      increased level of the type I receptor.
AB  - BACKGROUND: Cytokines, in particular IL-1, are believed to be responsible for
      mediating cartilage degradation in osteoarthritis (OA). To investigate the role
      of the IL-1 system in this disease, we studied in normal and OA human synovial
      fibroblasts the nature, the number, and the level of expression of the IL-1
      receptor (IL-1R) and through which receptor the biologic stimulation of these
      cells by IL-1 is mediated. EXPERIMENTAL DESIGN: We determined the IL-1R level by
      radioligand assay, the type of IL-1R with the use of specific antibodies and by
      the reverse transcriptase-PCR (RT-PCR), and the mRNA level of the type I IL-1R by
      slot blot analysis. Biologic activity was measured on the synovial fibroblasts
      via IL-1 binding and prostaglandin E2 production. RESULTS: Binding data revealed
      the presence of a single class of high affinity IL-1R in both normal (kD, 21 +/-
      4.5 pM) and OA (kD, 23 +/- 5.0 pM) human synovial fibroblasts. The number of
      receptors was significantly higher (p < 0.004) in OA synovial fibroblasts (2534
      +/- 187 sites/cell) than in normal cells (1310 +/- 96 sites/cell). This increase
      was transient; OA synovial fibroblasts in second and third passages had a normal
      level of IL-1R. Analysis of the mRNA species by RT-PCR revealed that both type I
      and type II IL-1R are coexpressed in normal and OA synovial fibroblasts; the type
      I mRNA was the most predominant in all samples. No difference in the relative
      amount of type I IL-1R mRNA level was found between normal and OA cells. A
      blocking Ab against the type I IL-1R completely inhibited, in both normal and OA
      cells, the receptor binding and IL-1 beta stimulated PGE2 production, whereas the
      treatment with anti-type II IL-1R was ineffective. CONCLUSIONS: These results
      indicate that the type I IL-1R is up-regulated in OA synovial fibroblasts and is
      responsible for mediating the biologic activation of these cells by IL-1. This
      phenomenon is probably secondary to an abnormality in the post-transcriptional
      regulation of the type I IL-1R. Although type II IL-1R is also expressed, its
      translation seems to be inoperative, or this receptor is already shed.

PMID- 7564268
TI  - Induction of atypical hyperplasia, apoptosis, and type II estrogen-binding sites
      in the ventral prostates of Noble rats treated with testosterone and
      pharmacologic doses of estradiol-17 beta.
AB  - BACKGROUND: We have previously shown that combined administration of testosterone
      (T) and a low dose of estradiol 17 beta (T+LDE2) for 16 weeks induces an atypical
      proliferative lesion, termed dysplasia, in the dorsolateral prostates of intact
      Noble rats (1, 2). The lesion was accompanied by increases in the levels of a
      moderate affinity, high capacity, estrogen-binding site (type II sites) found
      exclusively in dorsolateral prostates of these animals (1, 3). In contrast, a
      proliferative response and type II sites were not observed in the ventral
      prostates (VP) of the same rats treated with this hormonal regimen. In the
      current study, rats were treated with a higher dose of E2 (4 x LDE2) but the same
      dose of T (T+HDE2) for 16 weeks. Our aims were to determine how the VP would
      respond to the T+HDE2 treatment. EXPERIMENTAL DESIGN: Intact Noble rats were
      treated with T+HDE2 for 16 weeks. Prostatic tissues were removed for histology,
      electronmicroscopy, and type II site measurements. Proliferating cells were
      identified by the histochemical detection of proliferating cell nuclear antigen
      and colcemid-arrested mitotic figures. Apoptotic cells were recognized by their
      characteristic histologic and ultrastructural features and by in situ detection
      of nuclear DNA fragmentation. Data were compared with results previously obtained
      from VP of rats treated with T+LDE2. RESULTS: The VP of T+HDE2-treated animals
      contained focal atypical hyperplasia and wide-spread apoptosis. Proliferating
      cell nuclear Ag-positive-stained epithelial cells and mitotic figures were only
      present in foci of atypical hyperplasia. Total DNA content of the VP was
      significantly increased, but the tissue wet weight was not augmented. Nuclear
      type II sites, never observed in untreated or T+LDE2-treated rats, were detected
      in the VP of the majority of T+HDE2-treated animals. CONCLUSIONS: The
      administration of a high dose of E2 with T produced a unique lesion in the VP,
      characterized by simultaneous occurrence of apoptosis and proliferation. The
      synergy between androgens and estrogens, via type II site induction, likely
      produces the proliferative response. On the other hand, inhibition of
      intracellular androgen activation pathways, leading to reduction in cell survival
      factors, may be the cause for the apoptotic development. Our model, thus,
      provides a unique opportunity to further study the balance/switch between cell
      proliferation and apoptosis that is often disturbed during cancer development.

PMID- 7564269
TI  - The cell proliferation-associated protein Ki-67 is a target of autoantibodies in
      the serum of MRL mice.
AB  - BACKGROUND: Ab in the serum of patients with autoimmune diseases have been used
      to identify, characterize, and purify many autoantigens. EXPERIMENTAL DESIGN:
      Serum from a patient (Ge) with Sjogren's syndrome was used to identify cDNA
      clones encoding novel autoantigens. This patient's serum was chosen for study
      because it contained antinuclear Ab that were different from those frequently
      detected in patients with autoimmune diseases. RESULTS: Ge serum identified a
      cDNA clone encoding part of protein Ki-67, a cell proliferation-associated
      protein. The Ki-67 protein (pKi-67) was not previously known to be a target of
      autoantibodies. To investigate the association between Ab directed against pKi-67
      and autoimmune diseases, sera from autoimmune mice were tested for reactivity
      with a recombinant fragment of pKi-67. Ab were detected in serum from MRL/MpJ(
      )+/+ and MRL/MpJ-lpr/lpr mice but not in serum from other autoimmune mice or
      control animals. CONCLUSIONS: Protein Ki-67 joins the proliferating cell nuclear
      Ag (PCNA) as an example of a cell proliferation-associated protein that is a
      target of autoantibodies. The presence of anti-pKi-67 Ab in MRL mice, but not
      other autoimmune mice, suggests that anti-pKi-67 Ab may be specific markers for
      the systemic lupus erythematosus-like illness that develops in these animals.
      Further characterization of the immune response directed against this Ag may
      provide clues to the etiology and pathogenesis of autoimmune disease in these
      animals.

PMID- 7564270
TI  - High glucose alters actin assembly in glomerular mesangial and epithelial cells.
AB  - BACKGROUND: Glomerular mesangial and epithelial cell structure and function are
      maintained by cytoskeletal protein organization and function. To determine
      whether the diabetic milieu alters filamentous (F-) actin assembly, the spatial
      distributions and content of F- and monomeric (G-) actin were analyzed in rat
      mesangial and glomerular epithelial cells (10 to 15 passages) cultured for 5 days
      in high (22.4 mM) or normal (5.2 mM) glucose and in cells of whole glomeruli
      isolated from streptozotocin-treated diabetic or normal rats. EXPERIMENTAL
      DESIGN: Cells were labeled with the fluorescent probes rhodamine-phalloidin and
      FITC-DNase-1 specific for F- and G-actin, respectively. The average pixel
      intensities per cell were measured using dual channel confocal laser scanning
      microscopy (N = 60 cells per group). Total and G-actin were measured in mesangial
      cells by a spectrophotometric-based DNase-1 inhibition assay. RESULTS: In
      response to endothelin-1, 0.1 microM, vasopressin 1.0 microM, or angiotensin II
      1.0 microM, mesangial cells cultured in normal glucose displayed partial
      disassembly of F-actin characterized by decreased fluorescence intensity
      (microfilament bundle pattern changed to network) with no change in G-actin
      fluorescence. In high glucose, but not mannitol (22.4 mM), partial disassembly of
      F-actin and loss of response to the agonists were observed. In high glucose, the
      F-actin content (micrograms/mg cellular protein) was reduced significantly with
      no change in absolute G-actin compared with normal glucose exposure. The effect
      of high glucose on mesangial cell actin was reversed by returning the cells to
      normal glucose for 2 days, stimulation with insulin 2 micrograms/ml, or with a
      protein kinase C inhibitor. Mesangial cells in high glucose were smaller in
      planar area and exhibited loss of contractile response to endothelin-1 (0.1
      microM) or vasopressin (1.0 microM) measured by videomicroscopy. High glucose
      induced F-actin disassembly, possibly due to activated protein kinase C, could
      account for smaller cell size and lack of response to vasopressor agents.
      Glomerular epithelial cells cultured in normal glucose demonstrated F-actin
      disassembly and increased G-actin fluorescence intensity in response to A23187 (5
      microM) or bradykinin (10 nM). When cultured in high glucose, but not mannitol,
      increased epithelial G-actin fluorescence and loss of F- and G-actin response to
      agonists were observed. Although stimulation with insulin reversed the high
      glucose effect on epithelial G-actin, F-actin remained unresponsive to agonists.
      The cells of glomeruli isolated from the diabetic rat displayed the same increase
      in G-actin, no change in F-actin fluorescence, and loss of response to agonist
      stimulation as observed in cultured epithelial cells. CONCLUSIONS: These findings
      suggest that high glucose alters actin assembly in both glomerular mesangial and
      epithelial cells in vitro and in vivo, possibly contributing to cellular
      dysfunction in early diabetes.

PMID- 7564271
TI  - Cytokine production and visualized effects in the feto-maternal unit.
      Quantitative and topographic data on cytokines during intrauterine disease.
AB  - BACKGROUND: A large array of cytokines show high activity in amniotic fluid.
      Attempts have been made to quantify the concentrations or to track rising levels
      for diagnostic purposes when examining disturbances of the feto-maternal unit.
      However, the kinetics of cytokine production in the amniotic fluid are not well
      understood, and there is lack of knowledge about concomitant levels in fetal and
      maternal blood. EXPERIMENTAL DESIGN: The presence of cytokines in fetal and
      placental cells was demonstrated by immunohistochemistry using mAb. Cytokines
      were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal
      blood. This was done with regard to two disease states that quite frequently
      complicate the course of pregnancy, namely chorioamnionitis and intrauterine
      growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1,
      IL-6, and IL-8. RESULTS: In chorioamnionitis, all cytokines, except GM-CSF, were
      elevated about 100 times in the amniotic fluid. An accompanying increase in
      maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in
      fetal blood only. Intrauterine growth retardation was characterized by elevated
      levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta
      were significantly reduced. Immunohistochemistry showed that under normal
      conditions the cytokines are to be found in a characteristic distribution in
      certain cell types in the fetus, the placenta, and the placental bed. With rising
      concentrations, more cells seemed to be recruited for cytokine production,
      especially macrophages and decidual cells. In chorioamnionitis, fetal
      extramedullary granulopoiesis was augmented, and in intrauterine growth
      retardation, erythropoiesis as well as granulopoiesis were depressed.
      CONCLUSIONS: Not only inflammatory disease but also intrauterine growth
      retardation is characterized by a changing cytokine pattern. Alterations in fetal
      hematopoiesis observed at postmortem examination of perinatal deaths can be
      correlated to changes in cytokine production within the feto-maternal unit.

PMID- 7564272
TI  - Expression of extracellular matrix genes in adult human dermal microvascular
      endothelial cells and their regulation by heparin and endothelial cell mitogens.
AB  - BACKGROUND: Microvascular alterations are prominent features of systemic
      sclerosis (SSc) and often precede the appearance of clinically detectable
      fibrosis. The mechanism leading to selective microvascular injury in SSc is not
      known; however, microvascular endothelial cell (EC) activation has been
      demonstrated in SSc skin and is considered to be an early event in the
      pathogenesis of SSc. EXPERIMENTAL DESIGN: The expression of genes encoding
      extracellular matrix (ECM) proteins was examined in adult human dermal
      microvascular EC (HDMVEC), human iliac vein EC (HIVEC), and human umbilical vein
      EC (HUVEC) using indirect immunofluorescence (IIF) and Northern hybridization
      analysis. The effects of heparin and the endothelial cell mitogens, endothelial
      cell growth factor (ECGF) supplement and acidic and basic fibroblast growth
      factors (aFGF and bFGF), on the expression of ECM genes by these cells were also
      studied. RESULTS: Abundant transcripts for collagen types I, IV, VI, and
      fibronectin (FN) and weak expression of the type III collagen gene were detected
      in HDMVEC cultures in the absence of ECGF and heparin. In contrast, in the
      presence of these factors, no mRNA for types I, III, and VI collagens and marked
      down-regulation (more than twofold) of mRNA levels for collagen type IV and FN
      were observed. These results were confirmed at the protein level by IIF staining.
      In contrast to HDMVEC, HIVEC and HUVEC did not show expression of genes encoding
      types I, III, and VI collagens under any culture conditions examined. Next we
      studied the separate effect of heparin and aFGF or bFGF on the expression of ECM
      genes in HDMVEC. In contrast to the maximal expression of types I and VI
      collagens and FN detected in the absence of growth factors, aFGF decreased mRNA
      levels by 43% for type I collagen, by 52% for type VI collagen, and by 47% for
      FN. The decreases in mRNA levels caused by bFGF were 37, 41, and 36%,
      respectively. Heparin alone decreased the mRNA levels for these genes by 60, 77,
      and 65%, respectively; however, FGF potentiated the negative effect of heparin on
      ECM gene expression. CONCLUSIONS: These results demonstrate that HDMVEC display a
      unique pattern of expression of ECM genes that is different from that displayed
      by EC from medium and large vessels. The data also demonstrate that heparin, ECGF
      supplement, aFGF, and bFGF regulate ECM gene expression in HDMVEC in vitro and
      suggest that these growth factors may modulate the expression of matrix genes in
      vivo. Altered expression of ECM genes by HDMVEC may play an important role in
      diseases affecting the microvasculature, such as SSc.

PMID- 7564273
TI  - Reduced expression of platelet surface glycoprotein receptor IIb/IIIa at
      hyperthermic temperatures.
AB  - BACKGROUND: Hyperthermic temperatures exist from the heat dissipation of the
      implantable energy source of an artificial heart. This procedure as well as
      therapies for cancer and thermal injuries pose a new medical problem. Among many
      reported effects of heat on biologic systems, platelet functions such as maximal
      aggregation and adhesion are known to be reduced. Using flow cytometry, we have
      studied platelet dysfunction at elevated temperatures and have gained a
      mechanistic comprehension of the loss of platelet function. EXPERIMENTAL DESIGN:
      Platelet rich plasma was incubated at differing temperatures for 1 hour.
      Immediately after, the platelets were stained using mAb against glycoprotein
      IIb/IIIa (GPIIb-IIIa) (CD41a) and other platelet surface glycoproteins (GP)
      involved in aggregation and adhesion. Relative fluorescence intensity was
      measured using single-labeled, laser flow cytometry to determine changes in GP
      surface expression. In addition, scanning electron microscopy was used to
      evaluate morphologic changes. RESULTS: Hyperthermic temperatures between 40 and
      44 degrees C significantly lowered the mAb cell surface binding in vitro of GP
      that participate in aggregation and adhesion. The most dramatic temperature
      dependent loss of mAb binding was demonstrated by anti-GPIIb-IIIa, the mAb
      against the fibrinogen receptor. mAb binding to this receptor at 44 degrees C was
      decreased to 6.2% of a base-line fluorescence intensity of 654 (arbitrary units).
      The ADP-induced aggregation of platelets incubated at the same temperature also
      decreased to 2.1% of maximum aggregation. Other mAb, such as those against the
      von Willebrand factor receptor (GPIb) (CD42b), the thrombospondin receptor (GPIV)
      (CD36), and GPIIIa (CD61), also showed statistically significant reduction of mAb
      binding but to a lesser degree. Finally, scanning electron microscopy as well as
      side-scatter density plots from flow cytometry revealed that platelets became
      more spherical after incubation at 44 degrees C. CONCLUSIONS: The significant
      reduction in mAb binding correlates with functional impairment exhibited during
      hyperthermic incubation. Our results support the loss of binding ability of
      surface GP that are involved in aggregation and adhesion as a mechanism of
      platelet dysfunction upon heating. GPIIb-IIIa appeared the most susceptible to
      heat and the principal agent in thermal induced loss of platelet function.
      Significant morphologic changes at 44 degrees C, the critical temperature at
      which ADP-induced aggregation ceases, may contribute as well.

PMID- 7564274
TI  - Hepatocyte growth factor is a potent mitogen for normal human pancreas cells in
      vitro.
AB  - BACKGROUND: Little is known regarding the mechanisms that regulate cell
      proliferation in the exocrine pancreas. The aim of this study was to analyze the
      effect of growth factors on normal human exocrine pancreas cultures. EXPERIMENTAL
      DESIGN: The mitogenic effect of hepatocyte growth factor (HGF), insulin-like
      growth factor-1 (IGF-1), epidermal growth factor (EGF), and other growth factors
      was examined using [3H]-thymidine uptake assays. The phenotype of the cultures
      was analyzed using a panel of mAb. c-met expression was determined by
      immunohistochemistry and Western blotting. RESULTS: HGF was the most potent
      mitogen (concentration range 0.1 to 10 ng/ml), although IGF-1, EGF, and platelet
      derived growth factor were also mitogenic in some assays. Combinations of HGF+EGF
      or HGF+IGF-1 were superior to HGF when used at suboptimal concentrations.
      Proliferative cultures expressed cytokeratins 7, 8, 18, and 19 and the MUC1
      mucin, a phenotype characteristic of normal ductal cells. The 170-kDa precursor
      and 145-beta chain of c-met were detected in cultured cells with rabbit
      polyclonal antisera raised against synthetic peptides corresponding to the
      carboxy-terminal domains of the beta chain. c-met was also detected in the apical
      membrane of ductal cells in normal pancreas tissue but was generally absent from
      acinar, centroacinar, and islet cells. CONCLUSIONS: These results suggest that
      HGF and c-met may play a role in growth regulation in this organ.

PMID- 7564275
TI  - Susceptibility to lipid peroxidation of human hepatocellular carcinoma cell lines
      with different levels of multiple drug-resistant phenotype.
AB  - BACKGROUND: It has not been established whether the presence of intrinsic or
      acquired multiple drug-resistant (MDR) phenotype affects susceptibility to
      undergo iron-stimulated lipid peroxidation. EXPERIMENTAL DESIGN: To assess this
      point, human hepatocellular carcinoma cell lines with moderate, clinically
      relevant (P1) or elevated (P1(0.5)) MDR phenotype and their parental drug
      sensitive (P5) cell line were exposed to ADP-Fe or ascorbate-Fe complexes and
      H2O2 in different experiments. Thiobarbituric acid-reactive substances (TBARS)
      were measured. Total cell glutathione, glutathione-S-transferase, total and
      selenium-dependent glutathione peroxidase activities, and cell alpha-tocopherol
      content were also determined. RESULTS: P5 and P1 cell lines showed similar and
      significant formation of TBAR after 1-hour incubation exposure to iron complexes,
      whereas P1(0.5) subclone did not. No accumulation of TBAR was observed during the
      exposure to H2O2 in the three cell lines. Among antioxidants, only alpha
      tocopherol cell content was significantly higher in P1(0.5) in comparison with
      either P1 or P5. CONCLUSIONS: These data suggest that MDR phenotype development
      per se does not increase resistance to iron-related free radical attack in human
      hepatocellular carcinoma cell lines. Resistance to undergo lipid peroxidation is
      associated only to high degrees of drug resistance and appears more related to
      increased alpha-tocopherol cell content rather than an MDR phenotype.

PMID- 7564276
TI  - Bile duct-specific lectins, Dolichos biflorus agglutinin and peanut agglutinin,
      as probes in mouse hepatocarcinogenesis.
AB  - BACKGROUND: It is well established that alterations in the expression of cell
      surface glycoproteins occur during the course of tumorigenesis and can be
      detected immunohistochemically. However, no consistent markers of malignancy in
      mouse hepatocellular tumors have yet been identified. EXPERIMENTAL DESIGN: Lectin
      histochemistry, using three bile duct-specific lectins, Dolichos biflorus
      agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti
      epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin
      embedded tissues of a spectrum of benign and malignant hepatocellular
      proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA
      binding glycoproteins in normal livers and in bile and liver tumors of mice were
      verified by SDS-PAGE and Western blot analysis. RESULTS: Normal bile duct cells
      stained strongly with DBA but minimally to moderately with PNA and SBA. DBA
      positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of
      hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43%
      of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of
      hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain
      tumor cells. Normal hepatocytes and those in altered foci were consistently
      negative for these three lectins. Keratin-positive staining was found only in
      normal bile ductular cells and ductal elements in 70% of
      hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated
      that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa
      glycoproteins believed to be of bile duct cell origin and commonly present in
      hepatocellular adenomas, hepatocellular carcinomas, and
      hepatocholangiocarcinomas, with strongest expression in the last. In addition,
      hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200
      kDa) labeled with DBA as detected in bile. CONCLUSIONS: Our results suggest that
      some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have
      the potential of biliary differentiation. DBA is a sensitive marker for malignant
      hepatocytes in mice.

PMID- 7564277
TI  - Cell type-specific and inflammatory-induced expression of haptoglobin gene in
      lung.
AB  - BACKGROUND: Haptoglobin (HP) is a hemoglobin-binding protein and a major acute
      phase reactant. Recently, HP has been shown to possess antioxidant and angiogenic
      properties. HP is known to be produced mainly in the liver. Expression of HP in
      specific cells of nonhepatic origin including lung cells has not been studied
      before. The presence of extracellular plasma proteins in lung epithelial fluid
      has been assumed to be of blood serum origin. EXPERIMENTAL DESIGN: To investigate
      the expression of the HP gene in lung, the presence of HP mRNA and the production
      of HP protein in the lung were examined by Northern blot analysis and
      immunoprecipitation, respectively. Cellular expression of HP during development
      and inflammation were studied by in situ hybridization with lung tissues derived
      from different gestational stages from baboons and mice and from mice treated
      with lipopolysaccharide. RESULTS: Northern blot and in situ hybridization
      analyses established a high level of expression of HP in fetal and adult lung
      tissues, which were confined to the epithelial lining of the airways in mouse and
      baboon. After inflammation had been induced in vivo, expression of the HP gene
      rose fourfold in lung, an increase compatible with that observed in normal mouse
      liver. However, HP mRNA level was not significantly altered in airway epithelium.
      Instead, HP expression in alveolar epithelial cells, most likely type 2 cells,
      was strongly increased. CONCLUSIONS: Our data suggest that locally synthesized HP
      provides a major source of antioxidant and/or antimicrobial activity in the mucus
      blanket as well as in the alveolar fluid in the lung. The regulation and cell
      type-specific expression of HP during development and inflammation indicate a
      protective role for HP in lung and confirm recent reports that HP plays important
      roles in protecting against infection and in repairing injured tissues.

PMID- 7564278
TI  - Distribution and quantitation of lung parenchymal contractile tissue in ovine
      lentivirus-induced lymphoid interstitial pneumonia. Do tissue forces limit lung
      distensibility?
AB  - BACKGROUND: Lymphoid interstitial pneumonia (LIP) is frequently identified in
      sheep infected with the ovine lentivirus, maedi-visna virus (MVV). Functional
      consequences of this condition include a reduction in lung distensibility that
      cannot be explained by the density of surface forces within the lung parenchyma.
      A potential source of tissue forces to account for this functional deficit is the
      substantial parenchymal smooth muscle hyperplasia that is a feature of the lung
      pathology. This investigation examines the relationship between lung
      distensibility and the quantity and distribution of smooth muscle hyperplasia in
      MVV-induced LIP. EXPERIMENTAL DESIGN: Immunohistochemical localization of alpha
      smooth muscle actin (ASMA) was used to identify parenchymal contractile tissue.
      The distribution and morphometric quantitation of ASMA in lung parenchyma was
      determined in normal sheep lungs and in lungs from sheep seropositive for MVV.
      The relationship between the volume density of ASMA in lung parenchyma (Vv'ASMA')
      and static lung compliance (Cst) and lung distensibility (K) was examined.
      RESULTS: In normal lungs, ASMA was expressed by typical smooth muscle cells
      surrounding airways and blood vessels, by cells at the alveolar septal tips
      protruding into the alveolar ducts, and, rarely, by individual cells within
      septa. In MVV-seropositive sheep with minimal histopathology, increased ASMA
      expression occurred in association with early interstitial infiltrates and was
      located both at septal tips and within septa. With more severe pathology, ASMA
      expressing cells became organized into bundles within obviously thickened septa
      and septal tips. In maedi, Vv'ASMA' is negatively correlated with K and Cst (rs =
      -0.614; p < 0.005; and rs = -0.504; p < 0.025, respectively). However, partial
      correlation coefficients indicate that Vv'ASMA' and lung parenchymal tissue
      density (Vvt) are strongly interdependent. CONCLUSIONS: ASMA expression in normal
      sheep lung parenchyma follows a similar pattern of distribution to that described
      for human lungs. The quantity of ASMA in lung parenchyma in LIP associated with
      MVV infection is negatively correlated with lung distensibility; however, whether
      this is a causal association remains undetermined.

PMID- 7564279
TI  - Simultaneous exposure to nicotine and hyperoxia causes tumors in hamsters.
AB  - BACKGROUND: We have shown that the nicotine-derived nitrosamine 4-(methyl
      nitrosamino)-3-(pyridyl)-1-butanone (NNK) causes a high incidence of
      neuroendocrine lung tumors in male Syrian golden hamsters when administered to
      animals maintained in an atmosphere of 60% hyperoxia. In vitro studies with fetal
      hamster pulmonary neuroendocrine cells (PNE cells) and human neuroendocrine lung
      cancer cell lines revealed that nicotine and NNK are both potent mitogens for
      normal and neoplastic PNE cells when the cells were maintained in an atmosphere
      of high CO2. These effects were completely inhibited by antagonists of nicotinic
      acetylcholine receptors (nAChR). NNK displaced 3H-(-)L-nicotine from the nAchR in
      radioreceptor assays with cell membrane fractions from hamster lungs enriched in
      PNE cells. We therefore hypothesized that NNK acts as an agonist of the nAchR in
      PNE cells and that stimulation of this receptor in an environment of impaired
      pulmonary oxygenation is an important molecular event leading to the development
      of lung tumors with a neuroendocrine phenotype. EXPERIMENTAL DESIGN: To test this
      hypothesis, we exposed male Syrian golden hamsters maintained in 60% hyperoxia to
      s.c. injections of nicotine for the duration of their life. To allow for a
      survival time long enough to assess a potential carcinogenic effect of this
      treatment, animals demonstrating symptoms of respiratory distress were returned
      to ambient air for 24 hours throughout the experiment. RESULTS: A low but
      significant number of the animals exposed to hyperoxia and nicotine developed
      tumors of the nasal cavity, lungs, and adrenal glands. All of the tumor-bearing
      animals had survived 40 weeks or longer. The lung tumors demonstrated focal areas
      of positive immunoreactivity to neuron-specific enolase (NSE) and 5-hydroxy
      tryptamine (5-HT, serotonin), both of which are markers of neuroendocrine
      differentiation. Hamsters maintained in ambient air and receiving identical
      injections with nicotine as well as animals maintained in hyperoxia and injected
      with saline did not develop tumors in any organs. All hamsters exposed to
      hyperoxia and surviving more than 12 weeks had thickened alveolar walls and
      emphysema. CONCLUSIONS: Our data support the hypothesis that chronic stimulation
      of the nAChR in an environment of impaired pulmonary oxygenation contributes to
      the carcinogenic burden associated with exposure to cigarette smoke and provides
      selective growth advantage for lung tumors with a neuroendocrine phenotype.

PMID- 7564280
TI  - Infection and disease due to human immunodeficiency virus and the acquired
      immunodeficiency syndrome.

PMID- 7564281
TI  - AIDS: where do we stand?

PMID- 7564282
TI  - Bridging the "med-ed gap" for students with special health care needs: a model
      school liaison program.
AB  - A successful school experience is critical to the development of all children,
      particularly in the areas of academic achievement, regular school attendance, and
      social competency. Vulnerabilities in achieving each of these three goals have
      been documented among students with special health care needs (SSHCN), and
      ascribed to the influence of their health-related disabilities. Despite
      recognition of these vulnerabilities, barriers still exist to successful
      integration of SSHCN into educational settings. A key barrier to successful
      integration involves poor linkages between the health and education systems. This
      article describes a model linkage system--the School Liaison Program at Texas
      Children's Hospital, developed as a U.S. Dept. of Health and Human Services
      Maternal and Child Health Bureau Special Project of Regional and National
      Significance. The program provides educational liaison services between the
      largest pediatric hospital in the United States and school districts in the
      fourth largest city. A description of the linkage system emphasizes
      interdisciplinary staffing by both special educators and health providers. The
      model for educational liaison service delivery presented includes the elements of
      eligibility, assessment of the educational implications of illness, plan
      development and referral, involvement in educational placement, and monitoring.
      Resources for integrating SSHCN into educational settings are suggested.

PMID- 7564283
TI  - Gender and developmental differences in exercise beliefs among youth and
      prediction of their exercise behavior.
AB  - This study examined gender and developmental differences in exercise-related
      beliefs and exercise behaviors of 286 racially diverse youth and explored factors
      predictive of exercise. Compared to males, females reported less prior and
      current exercise, lower self-esteem, poorer health status, and lower exercise
      self-schema. Adolescents, in contrast to pre-adolescents, reported less social
      support for exercise and fewer exercise role models. In a path model, gender, the
      benefits/barriers differential, and access to exercise facilities and programs
      directly predicted exercise. Effects of grade, perceived health status, exercise
      self-efficacy, social support for exercise, and social norms for exercise on
      exercise behavior, were mediated through the benefits/barriers differential.
      Effect of race on exercise was mediated by access to exercise facilities and
      programs. Continued exploration of gender and developmental differences in
      variables influencing physical activity can yield valuable information for
      tailoring exercise promotion interventions to the unique needs of youth.

PMID- 7564284
TI  - Drug use, sexual activity, and suicidal behavior in U.S. high school students.
AB  - Data from the 1990 Youth Risk Behavior Survey were used to examine the
      interrelationship of drug use, sexual activity, and suicidal behavior in U.S.
      high school students. Findings indicated adolescents who engaged in substance use
      and/or sexual activity were more likely to experience suicide ideation and
      behavior than those who abstained from such activities. Data analysis revealed a
      significant and positive relationship between cocaine use and severity of
      outcomes of suicide attempts. Marijuana use and alcohol use were related to
      suicide behavior, but these relationships were not as strong as those noted for
      cocaine use. The study also revealed a positive relationship between frequency of
      sexual activity and attempted suicide, but could not determine whether such
      sexual activity was coerced, forced, or voluntary in nature.

PMID- 7564285
TI  - The influence of parental smoking on youth smoking: is the recent downplaying
      justified?

PMID- 7564286
TI  - The top 10 healthy list.

PMID- 7564287
TI  - School nurses' experiences with children with chronic conditions.

PMID- 7564288
TI  - Trends in sexual risk behavior among high school students--United States, 1990,
      1991, and 1993.

PMID- 7564289
TI  - Urine concentrations of ecgonine from specimens with low benzoylecgonine levels
      using a new ecgonine assay.
AB  - A new approach to detecting drug positives for cocaine in urine having
      benzoylecgonine concentrations below the Department of Defense (DoD) cutoffs was
      examined by measuring the concentrations of the metabolite ecgonine. The DoD
      cutoff concentrations for determining a positive for cocaine are 150 and 100
      ng/mL for radioimmunoassay and gas chromatography-mass spectrometry,
      respectively. To facilitate this approach, a new assay was developed for ecgonine
      using only 1 mL urine. The urine was passed through an anion-exchange cartridge,
      and the eluant was evaporated to dryness in a water bath under nitrogen. The
      residue was subjected to nonylation and a standard back extraction procedure
      before a second derivatization with propionic anhydride. A total of 139 urine
      specimens were analyzed in this manner, and 104 yielded ecgonine concentrations
      greater than 50 ng/mL. The average ecgonine concentration in the latter specimens
      was approximately 5 times the comparable benzoylecgonine concentration. By
      monitoring ecgonine alone or in conjunction with benzoylecgonine, the number of
      cocaine positives detected in urine could be dramatically increased.

PMID- 7564291
TI  - Meconium analysis for cocaine: a validation study and comparison with paired
      urine analysis.
AB  - We established the validity of a drug-screening method to detect the presence of
      cocaine or benzoylecgonine or both in meconium and then undertook an analysis of
      results from urine and meconium specimens obtained concurrently from neonates
      within 3 days of birth. Meconium specimens from 82 consecutive newborns were
      analyzed using fluorescence polarization immunoassay (FPIA), Kinetic Interaction
      of Microparticles in Solution (KIMS), and gas chromatography-mass spectrometry
      (GC-MS). Each meconium specimen was analyzed by all three methods. Fifty-four
      paired urine and meconium specimens were obtained over a 13-month period from a
      neonatal intensive care unit. Urine drug testing was performed by immunoassay
      (enzyme multiplied immunoassay [EMIT] technique), whereas meconium specimens
      utilized FPIA with GC-MS confirmation on all but one specimen (due to
      insufficient quantity). Ten true positives were found by GC-MS, 10 positives were
      found by FPIA, and 70 positives were found by KIMS. Of the 54 paired samples, 39
      samples tested negative for cocaine in both urine and meconium; four specimens
      were positive by both routes; 10 specimens were negative in urine but positive in
      the meconium; and one specimen tested positive in urine but negative in the
      meconium. Thus, 9.3% of the urine specimens tested positive, and 25.9% of
      meconium samples tested positive (p = .011; McNemar's Test). We conclude that
      screening meconium specimens by FPIA followed by GC-MS confirmation of screened
      positives yields highly accurate determinations of the presence of cocaine or
      benzoylecgonine or both in meconium and that testing of meconium for cocaine and
      its metabolites is more sensitive than testing of urine.

PMID- 7564290
TI  - Separation and quantitation of the enantiomers of methamphetamine and its
      metabolites in urine by HPLC: precolumn derivatization and fluorescence
      detection.
AB  - To study the disposition kinetics of methamphetamine (MAP), we have developed a
      sensitive high-performance liquid chromatographic (HPLC) assay to quantitate the
      enantiomers of MAP and its major metabolites, amphetamine (AP), p
      hydroxymethamphetamine (p-OH-MAP), and p-hydroxyamphetamine (p-OH-AP), the latter
      two of which are hydroxylated metabolites, in rat urine. To determine conjugated
      hydroxylated metabolites, urine samples were treated with beta-glucuronidase.
      Both hydrolyzed and nonhydrolyzed p-OH-MAP and p-OH-AP were extracted into ethyl
      acetate and back extracted with 0.05M HCl. To determine MAP and AP, urine samples
      were extracted with benzene, followed by back extraction into 0.05M HCl. The acid
      layer was collected, and to it was added (-)-1-(9-fluorenyl)ethyl chloroformate
      (FLEC) for the derivatization of MAP and its metabolites. Derivatization was
      allowed to proceed for 24 h at room temperature. The derivatized products were
      separated on a C18 column with a mobile phase consisting of acetate buffer (pH
      3.6)-acetonitrile-tetrahydrofuran. Quantitation was achieved using a fluorescence
      detector at an excitation wavelength of 265 nm and an emission wavelength of 330
      nm. Linear standard curves were obtained over the concentration range of 5-100
      ng/mL. The interday and intraday coefficients of variation for the assay for all
      eight enantiomers at 10 and 75 ng/mL were less than 13%. The detection limit was
      5 ng/mL or 0.5 ng on-column.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564292
TI  - A high-performance liquid chromatographic method for determining [3H]T-2 and its
      metabolites in biological fluids of the cynomolgus monkey.
AB  - High-performance liquid chromatography (HPLC) was used to separate, identify, and
      quantitate the trichothecin mycotoxin, T-2 (4 beta,15-diacetoxy-3 aopha-hydroxy-8
      alpha [3-methyl-butyryloxy]-12,13-epoxy delta 9-trichothecin), and its
      metabolites in plasma and urine samples from cynomolgus monkeys treated with the
      toxin. A 15-min gradient elution system was developed to separate and measure
      radiolabeled T-2 mycotoxin and its metabolites. The HPLC technique for separating
      T-2 and its metabolites was compared with thin-layer chromatography. Samples from
      the in vitro metabolism of T-2 by plasma and urine were included as controls and
      as a measure of the toxin's stability in biological samples. Within 5 min, 22% of
      the plasma radiolabeled T-2 toxin was detected as metabolites after an
      intravenous administration of [3H] T-2 toxin to cynomolgus monkeys. By 24 h post
      exposure, there was no parent T-2 toxin detected in plasma or urine. T-2 tetraol
      was the major metabolite detected in the plasma and urine of monkeys. Other
      metabolites observed in urine up to 5 days after exposure were 3'OH-T-2 and 3'OH
      HT-2. We conclude that T-2 toxin was rapidly metabolized to more polar
      metabolites, which were eliminated in urine.

PMID- 7564294
TI  - Morphine and morphine glucuronides in serum of heroin consumers and in heroin
      related deaths determined by HPLC with native fluorescence detection.
AB  - A simple, rapid, and sensitive high-performance liquid chromatographic method for
      the simultaneous determination of serum morphine, morphine-6-glucuronide (M6G),
      and morphine-3-glucuronide (M3G) based on native fluorescence detection is
      described. For the extraction of drugs and their metabolites, 200 microL serum
      was applied to 50 mg of a commercially available octylsilan phase. After
      isocratic separation in two steps (6.5 min) by reversed phase, the compounds were
      determined at an excitation wavelength of 245 nm and an emission wavelength of
      345 nm (the limit of detection was approximately 5 micrograms/L for each
      compound). The concentrations of morphine, M6G (with respect to its potential
      analgesic activity), and M3G were investigated in 20 heroin addicts in police
      custody and in 10 heroin-associated deaths. The ratios between M6G or M3G and the
      morphine concentrations and between M6G and M3G are related to the morphine
      concentration and consequently depend on the time elapsed since the last
      administration of morphine or heroin. Consequently, the M6G values were found to
      be higher in cases of death than in the living addicts. By considering the
      M6G/morphine or M3G/morphine ratios, the narcotic effect of heroin as reflected
      by morphine and its metabolite concentrations in impaired addicts and cases of
      fatal poisoning can be better assessed than by use of the morphine concentration
      alone.

PMID- 7564295
TI  - Measuring ethanol in saliva with the QED enzymatic test device: comparison of
      results with blood- and breath-alcohol concentrations.
AB  - An enzymatic test device, QED (quantitative ethanol detector), intended for on
      the-spot analysis of ethanol not equal to saliva was evaluated in laboratory
      experiments. Tests were made in vitro with known-strength aqueous ethanol
      standards and also in vivo after healthy volunteers drank a moderate dose of
      alcohol (0.80 g/kg), either on an empty stomach or after breakfast. Acetone,
      methanol, 2-butanone, and ethylene glycol did not react with the QED when tested
      in vitro. However, n-propanol (100 mg/dL) gave an apparent ethanol response of 60
      mg/dL; the secondary alcohol, 2-propanol (100 mg/dL), gave a response of 20
      mg/dL, but a longer time was needed to reach an endpoint. When ethanol solutions
      of 50, 100, and 140 mg/dL were analyzed, the QED gave readings of 50 +/- 2 (+/-
      standard deviation [SD]), 102 +/- 3, and 136 +/- 5, corresponding to recoveries
      of 100, 102, and 97%, respectively. The analytical precision, expressed as
      coefficients of variation, ranged from 3.2-4.0%. The mean difference between the
      QED test result and venous blood ethanol was 4.4 +/- 0.91 mg/dL (+/- standard
      error [SE]), and the 95% limits of agreement (LOA) were -18 and 26 mg/dL. The QED
      saliva test also compared well with breath-alcohol readings; the mean difference
      was 3.3 +/- 0.71 mg/dL, and the 95% LOA were now slightly narrower: -12 and 19
      mg/dL. The QED device proved useful for quickly analyzing alcohol in saliva, and
      the results agreed well with the concentrations of ethanol in venous blood and
      end-expired breath.

PMID- 7564296
TI  - Testosterone administration to mares: criteria for detection of testosterone
      abuse by analysis of metabolites in plasma and urine.
AB  - A pharmacological dose of a long-acting testosterone ester, testosterone
      hexahydrobenzoate, was administered intramuscularly to two mares. The time course
      for some characteristic metabolites in blood and urine was then studied using an
      analytical method based on gas chromatography-mass spectrometry associated with
      stable isotope dilution. Among the plasma analytes, testosterone glucuronide was
      found to be the most adequate indicator for the monitoring of exogenous
      testosterone up to 2 weeks postadministration if a threshold value of 200 ng/L
      was applied. In urine, the simultaneous measurement of the concentrations of
      testosterone sulfate (TS) and epitestosterone sulfate (ES) allowed the
      calculation of the concentration ratio, TS/ES, which was independent of urine
      flow and which offered the possibility of detecting testosterone misuse 20 to 30
      days after dosing if a tentative threshold value of 8 was adopted. In addition to
      this ratio, particularly when the TS/ES ratio was close to the cutoff point, it
      seemed advisable to take into account the concentrations of 5 alpha-androstane-3
      beta, 17 alpha-diol (glucuronide) and its 17 beta-isomer (sulfate), which should
      not exceed 50 micrograms/L.

PMID- 7564293
TI  - Comparison of the hydrolysis rates of morphine-3-glucuronide and morphine-6
      glucuronide with acid and beta-glucuronidase.
AB  - The acid and enzymatic hydrolysis rates for two morphine metabolites, morphine-3
      glucuronide (M3G) and morphine-6-glucuronide (M6G), were compared. Urine
      fortified with M3G or M6G was hydrolyzed in a boiling water bath or with beta
      glucuronidases. Optimal temperatures for beta-glucuronidases were 60 degrees C
      for Helix pomatia and abalone and 50 degrees C for Escherichia coli. A 3-h
      incubation with 1,000-1,500 Fishman units of enzyme gave complete hydrolysis of
      M3G. The enzymatic hydrolysis rate of M6G was approximately 25% of the hydrolysis
      rate of M3G and required 24 h for completion. The acid hydrolysis rate of M6G was
      slower than M3G and required a 0.5-h incubation with a 1:1 mixture of
      concentrated HCl in a boiling water bath for completion. For comparison, the acid
      hydrolysis rate of codeine conjugates was found to be similar to the rate of M6G,
      but the enzymatic rate of codeine conjugates appeared slower than the rate of
      M6G.

PMID- 7564297
TI  - Determination of triamcinolone acetonide in equine serum and urine by liquid
      chromatography-atmospheric pressure ionization mass spectrometry.
AB  - Urine and serum samples collected from four standard-bred mares after 30-mg
      intraarticular administrations of triamcinolone acetonide were analyzed using
      combined high-performance liquid chromatography-atmospheric pressure ionization
      mass spectrometry. Maximum triamcinolone acetonide concentrations of 32.3, 14.8,
      24.3, and 29.4 ng/mL in the urine and 2.7, 1.9, 2.3, and 2.5 ng/mL in the serum
      samples were observed. The peak concentrations of the drug were detected
      approximately 22 h (urine) and 12 h (serum) after administration. The drug
      elimination profiles for both urine and serum are presented and discussed.

PMID- 7564298
TI  - Measurement of methyl tert-butyl ether and tert-butyl alcohol in human blood by
      purge-and-trap gas chromatography-mass spectrometry using an isotope-dilution
      method.
AB  - We developed an isotope-dilution method for measuring methyl tert-butyl ether
      (MTBE) and tert-butyl alcohol (TBA) in whole human blood using a purge-and-trap
      gas chromatographic-mass spectrometric method. The labeled analogues for MTBE and
      TBA were [2H12]methyl tert-butyl ether and [2H9]-tert-butyl alcohol,
      respectively. Volatiles were removed from the blood by direct helium purging of
      the liquid; were trapped on a Tenax trap; and were desorbed, cryofocused, and
      chromatographed on a DB-624 capillary column that was connected directly to the
      ion source of a mass spectrometer. Detection was by mass analysis using a double
      focusing magnetic-sector mass spectrometer operating in the full-scan mode at the
      medium mass resolution of 3000. For the isotope-dilution method, the minimum
      detection limits in blood (5-10 mL) are 0.01 microgram/L for MTBE and 0.06
      microgram/L for TBA. The isotope-dilution method proved to be a big improvement
      in recovery, reproducibility, and sensitivity over our previous analytical
      method, which used the labeled ketone, [4-2H3]-2-butanone, as the internal
      standard for both MTBE and TBA. The isotope-dilution method has sufficient
      sensitivity for monitoring blood levels of MTBE and TBA in populations exposed to
      oxygenated fuels containing MTBE.

PMID- 7564299
TI  - Serum-ethanol determination: comparison of lactate and lactate dehydrogenase
      interference in three enzymatic assays.
AB  - Gas chromatography is considered to be the reference method for ethyl alcohol
      determination. However, enzymatic ethanol assays have been developed for use in
      the clinical laboratory by several commercial vendors. Essentially, these assays
      utilize the oxidation of ethyl alcohol to acetaldehyde with concurrent reduction
      of nicotinamide adenine dinucleotide (NAD) to NADH while monitoring the increase
      in absorbance at 340 nm. The increase in absorbance is theoretically proportional
      to the ethanol concentration in the sample. Previously, several authors reported
      that increased concentrations of lactate and lactate dehydrogenase (LDH) can
      cause false-positive results with certain enzymatic ethyl alcohol assays. In the
      present investigation, we further studied the interference of lactate and LDH in
      three enzymatic assays. Apparent ethyl alcohol concentrations in serum spiked
      with lactate and LDH, as well as patient and autopsy samples, were determined by
      the Syva, Abbott, and Roche enzymatic assays and by gas chromatography. The
      effect of coenzyme depletion on the rate of reaction and the interference of
      hemolysis were also investigated. Based on our results we suggest that coenzyme
      depletion plays a major role in the severity of the false-positive ethyl alcohol
      result, and the interference from hemolysis has a negligible effect on these
      results. We also confirm the previous studies in showing that elevated serum
      lactate and LDH concentrations can result in varying degrees of false-positive
      ethyl alcohol concentrations in the three enzymatic assays. This should be taken
      into consideration in the management of patients in a tertiary care medical
      center.

PMID- 7564301
TI  - Presence of rifampicin in urine causes cross-reactivity with opiates using the
      KIMS method.

PMID- 7564300
TI  - Analysis of diethyltoluamide (DEET) following intentional oral ingestion of
      Muscol.
AB  - N,N-Diethyl-m-toluamide (DEET) is an effective component of several insect
      repellent products. A 19-year-old woman was admitted to the emergency department
      following ingestion of 15-25 mL 95% diethyltoluamide (Muscol). Serum and urine
      toxicology screening tests were negative except for detection of DEET. DEET was
      qualitatively identified and quantitated by gas chromatography-mass spectrometry.
      Concentrations of DEET based on selected ion monitoring (ion at m/z 119) were
      63.0, 17.2, 1.9, and less than 0.2 mg/L in serum specimens collected at 2, 5, 24,
      and 48 h following ingestion, respectively. Serial monitoring of DEET
      concentrations and the cardiac abnormalities observed in this case following oral
      ingestion were not reported previously.

PMID- 7564302
TI  - Comparison of urine and hair testing for drugs of abuse.

PMID- 7564303
TI  - Affect and memory in advertising: an empirical study of the compensatory
      processes.
AB  - The influence of the affect dimensions (a) source identification, (b)
      attractiveness, and (c) fear appeal on memorization of a message by advanced
      Canadian students was investigated. Professionally designed commercials were used
      for the experiment. The results indicate a strong relationship between the three
      affective variables of the communication and the number of items in the
      respondents' memory. Two-way interactions between (a) attractiveness and
      identification and (b) attractiveness and fear were significant, as was the three
      way interaction.

PMID- 7564304
TI  - Stressful life events and psychological status in black South African women.
AB  - The relationship between stressful life events and psychological status in Black
      South African women was explored, using a semistructured interview that consisted
      of a demographic questionnaire; the Xhosa Life Event Scale (XLES; Swartz, Elk,
      Teggin, & Gillis, 1983), which comprises mainly personal stressors; the Township
      Life Event Scale (TLES; Bluen & Odesnik, 1988), which comprises mainly
      sociopolitical stressors; and the General Health Questionnaire (GHQ, Goldberg,
      1972, 1978). The participants were a random sample of 100 Black women living in a
      South African township. There were significant positive correlations between
      psychological distress and (a) undesirable life changes, (b) recurring stressful
      events of a sociopolitical nature (but not of a personal nature), and (c)
      continuous stressful events of a sociopolitical nature (but not of a personal
      nature). The results indicated that adverse sociopolitical conditions and the
      stress that accompanied them had a stronger negative effect than stressful events
      of a personal nature did on the women's mental health.

PMID- 7564305
TI  - Demographic characteristics of subjective age.
AB  - The relationships between subjective age and (a) gender, (b) marital status, (c)
      education, (d) income, and (e) race were examined, using data from two U.S. adult
      samples. None of these demographic characteristics were systematically related to
      any dimension of subjective age, suggesting that other characteristics are
      responsible for variation in subjective age.

PMID- 7564307
TI  - Family variables as mediators of the relationship between work-family conflict
      and marital adjustment among dual-career men and women.
AB  - Selected social-psychological processes within the family were examined as
      potential mediators of the relationship between work-family conflict and marital
      adjustment among career men and women in the United States. Seventy-nine men and
      198 women who were professionals in psychology participated in the study. A path
      analytic model was used to test two specific family variables--perceptions of
      equity in spousal home division of labor and perceptions of spousal social
      support--as potential mediators of the proposed negative relationship between
      work-family conflict and marital adjustment. Spousal social support and equity in
      spousal home division of labor played an important, albeit small, mediating role
      in the negative relationship between work-family conflict and marital adjustment
      for men and women. Contrary to expectations, gender exhibited no overall indirect
      effect on marital adjustment.

PMID- 7564306
TI  - Passionate love and anxiety: a cross-generational study.
AB  - This study was designed to assess whether the experience of passionate love would
      change as a consequence of development throughout adulthood and whether highly
      anxious people would be especially motivated to seek passionate love
      relationships. The Passionate Love Scale and the State-Trait Anxiety Inventory
      were administered to a cross-generational sample (total N = 255) of adolescents,
      young adults, middle-aged adults, and elderly in the United States. Status of
      past and present relationships was also determined. Contrary to expectations, no
      age-related differences were found for overall PLS scores. Moreover, the
      anticipated correlation between anxiety and passionate love was found only in the
      adolescent sample. A regression analysis revealed that for all age groups,
      whether or not a person was currently experiencing a passionate love relationship
      was the best predictor of scores on the PLS. These findings suggest a
      reconceptualization of passionate love as a life-span construct, rather than as a
      phenomenon largely confined to the period of adolescence.

PMID- 7564308
TI  - The birth order factor: ordinal position, social strata, and educational
      achievement.
AB  - The relationship between birth order and academic attainment of 817 men and women
      from a variety of socioeconomic backgrounds in the United States was explored. A
      measure of respondents' family economic situation during their growing-up years
      was incorporated. Birth order was found to have an impact on total years of
      education completed among members of the middle class. The observed patterns also
      indicate that "only" children, contrary to findings of previous research, appear
      disproportionately to excel in terms of educational attainment. These findings
      support a resource-dilution hypothesis.

PMID- 7564309
TI  - Cross-cultural, gender, and age differences in Singaporean mothers' conceptions
      of children's intelligence.
AB  - The effect of mothers' ethnic affiliation on their conceptions of children's
      intelligence was examined. Seven hundred eight Singaporean mothers of Chinese,
      Malay, and Indian ethnic origin responded to a 55-item questionnaire. For each
      item, the respondents indicated, on a 9-point scale, how typical they thought the
      specified behavior was for an intelligent child. There was a high level of
      similarity among the factor structures of the three subsamples, but several
      specific intergroup differences indicated that the mothers' conceptions of
      children's intelligence were affected to a certain extent by their ethnic
      affiliations and by the age and the sex of the child.

PMID- 7564310
TI  - Public and private attributions to luck as a function of social anxiety.

PMID- 7564311
TI  - Energy depletion in the liver and in isolated hepatocytes of tumor-bearing
      animals.
AB  - Cancer cachexia has a great impact on morbidity and mortality in patients
      undergoing surgery. Failure to maintain lean tissue against tumor-induced
      hypermetabolism results in cumulative weight loss and ultimate failure of the
      host. Cellular free energy is among the factors that regulates metabolic pathways
      and may be altered in the tumor-bearing state. We studied in-vivo and in-vitro
      ATP levels and metabolic parameters in Fischer rats bearing a methylcholanthrene
      induced sarcoma to elucidate the energy state. Tissue ATP was measured in freeze
      clamped liver and muscle in 15 tumor-bearing rats (TBR) at different tumor
      burdens and their pair-fed controls (CTR) by bioluminescence assay. Plasma
      metabolites, hormones, and enzymes were determined in the same animals. Liver ATP
      level was lower in TBR with a 5% tumor burden: 3.07 +/- 0.56 (SE) nmole/mg tissue
      vs CTR: 5.33 +/- 0.60 (P < 0.05), 10% TBR: 2.48 +/- 0.54 vs CTR: 4.05 +/- 0.63
      (n.s.), and 20% TBR: 1.91 +/- 0.21 vs CTR: 3.86 +/- 0.40 (P < 0.01). Muscle ATP
      was not different between TBR and CTR. This progressive loss of liver ATP was
      associated with decreased plasma insulin level (P < 0.001) and with increased
      alkaline phosphatase level (P < 0.01) by multiple regression. In vitro,
      hepatocytes were isolated from 8 TBR and 8 CTR by in-situ liver perfusion with
      collagenase and the cellular ATP was measured before and after 60 min incubation
      with glucogenic substrates. Hepatocytes from TBR decreased ATP by 42% (P < 0.05)
      in 10 mM lactate with higher gluconeogenesis, while control hepatocytes
      maintained the ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564312
TI  - Pharmacokinetics of endotoxin in a rhesus macaque septic shock model.
AB  - Using a prospective, randomized, controlled study, we tested the hypothesis that
      the initial administered dose of endotoxin determines its pharmacokinetics in a
      rhesus macaque septic shock model. Twelve adult male rhesus macaques, weighing 6
      to 10 kg, were equally divided into two groups. The first group received a 20
      mg/kg intravenous bolus of the gram-negative endotoxin. The second group received
      a bolus comparable to the concentration of endotoxin found in the plasma of the
      first group, 12 hr postendotoxin injection. Both groups were monitored for 12 hr
      and sacrificed. Plasma endotoxin concentrations were measured using the limulus
      amebocyte lysate assay and a pharmacokinetic model was applied to the
      concentration curves. Results of the pharmacokinetic evaluation revealed
      differences in half-life, clearance, and total apparent volume of distribution
      between the two groups of animals, suggesting that the changes in these
      parameters may have a biphasic pattern and may be related to the initial dose of
      endotoxin injected.

PMID- 7564313
TI  - University of Wisconsin solution effects on intimal proliferation in canine
      autogenous vein grafts.
AB  - This study was carried out to investigate if the University of Wisconsin solution
      (UWs) is suitable for long-term preservation of autogenous vein grafts (AVG)
      prior to transplantation, compared to autologous whole blood (AWB) and normal
      saline (NS). Autogenous jugular and femoral veins were harvested from adult
      mongrel dogs, using a "no-touch" technique. One segment of vein was immediately
      implanted to serve as a control, while other segments were stored for 24 hr at 4
      degrees C in AWB, NS, or UWs. The control and the preserved veins were implanted
      as reversed interposition grafts in the common carotid or femoral artery
      positions. After 6 weeks, scanning electron microscopy revealed an intact
      endothelial cell monolayer in all vein grafts that was stained positively for
      factor VIII. The degree of intimal thickening, as assessed by light microscopy in
      the middle position of the grafts, was similar in controls (52.0 +/- 15.8
      microns) and in veins stored in UWs (58.5 +/- 16.1 microns), but it was
      significantly increased (P < 0.05) in veins preserved in NS (198.9 +/- 19.5
      microns) and in AWB (312.0 +/- 171.6 microns). Isometric tension studies revealed
      that maximum contraction and sensitivities (assessed by EC50) to norepinephrine
      were significantly reduced (P < 0.05) in AVG stored in AWB (0.05 +/- 0.02 g/mm2
      and 5.5 +/- 2.8 microM), but not in UWs (0.16 +/- 0.03 g/mm2 0.92 +/- 0.34
      microM) and NS (0.09 +/- 0.03 g/mm2 and 3.0 +/- 1.1 microM), compared with
      controls (0.17 +/- 0.03 g/mm2 and 0.99 +/- 0.38 microM). Acetylcholine (Ach)
      induced maximum relaxations were similar in all of the veins.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7564314
TI  - Inferior rectal nerve stimulation for anal sphincteric control: experimental
      study.
AB  - The effect of inferior rectal nerve (IRN) stimulation on sphincteric control of
      the rectal neck was studied in eight dogs. With the dog under anesthesia, the IRN
      was exposed through para-anal incision, and a bipolar electrode was applied to
      it. Response of the rectal and rectal neck pressures as well as external and
      sphincter (EAS) EMG activity to IRN stimulation was determined. IRN stimulation
      resulted in increase in both the rectal neck pressure (P < 0.01) and the EMG
      activity of EAS (P < 0.01). Response increased with increasing stimulation
      frequency up to 50 Hz, above which no more response occurred. Rectal pressure
      showed no change (P > 0.05). Both the latency and the duration of response
      decreased with increased stimulation. The response was resumed after an off-time
      of twice the stimulation phase. Long-term activation has not been associated with
      an impairment of nerve responsiveness or with electrode migration or break. To
      conclude, a stimulus of 50 Hz evokes the most adequate EAS contraction and RN
      pressure elevation. Chronic electrostimulation of the perineal nerve may restore
      EAS tone.

PMID- 7564315
TI  - The beneficial effects of immunostimulation in posttraumatic sepsis.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) is a myelopoietic
      cytokine that may enhance immune mechanisms directed against bacterial infection.
      Injury is associated with an increased incidence of such infection. This study
      assessed the potential immunostimulatory role of GM-CSF in the injured host
      predisposed to infection. Six- to eight-week old female CD-1 mice underwent
      trauma and were then randomized to received either GM-CSF or saline vehicle
      control intraperitoneally for 5 days. They then received a septic challenge in
      the form of a cecal ligation and puncture. Following this, assessment was made of
      survival and bacterial growth indices in blood cultures, and peritoneal cells
      were harvested for assessment of peritoneal immune function. Intraperitoneal GM
      CSF administration daily for 5 days following injury was associated with
      significantly greater survival following cecal ligation and puncture compared to
      controls (40 vs 5%, P < 0.05). There was a significant increase in peritoneal
      cell yields in the GM-CSF group compared to the control group (11 +/- 1 x 10(6)
      vs 8 +/- 1 x 10(6) P < 0.05). PMA-stimulated macrophages released significantly
      higher amounts of both superoxide anion (1.4 +/- 0.1 vs 0.93 +/- 0.1, P < 0.05)
      and tumor necrosis factor (5.2 +/- 0.6 vs 2.6 +/- 0.7, P < 0.03) and
      significantly less nitric oxide compared to the control group (175 +/- 8 vs 267
      +/- 24, P < 0.003). Finally, bacterial growth indices were significantly reduced
      following GM-CSF administration (194 +/- 6 vs 218 +/- 4, P < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564316
TI  - Do results justify an aggressive strategy targeting the pedal arteries for limb
      salvage?.
AB  - We initiated a strategy to bypass all of the significant popliteal and tibial
      disease in the setting of limb-threatening ischemia beginning in September 1986.
      Of 194 infrapopliteal bypasses performed for limb salvage during the ensuing 6
      years, 111 (57%) autogenous vein bypasses were performed to the pedal vessels at
      or distal to the ankle. By life table analysis, primary graft patency at 60
      months for pedal bypasses was 57%, with salvage of failed grafts resulting in
      secondary patency of 61%. Limb salvage was 64% at 60 months. Of 33 graft
      thromboses, 24 (73%) resulted in eventual limb loss. Five limbs were amputated
      due to wound complications or progressive forefoot sepsis despite patent pedal
      grafts. More bypasses were performed to the dorsalis pedis than the posterior
      tibial at the ankle (78 vs 33), but patency and limb salvage were similar.
      Bypasses to the pedal arteries resulted in superior limb salvage compared with
      peroneal bypass when forefoot tissue necrosis was present (63 vs 33% at 36
      months, P = 0.048). Pedal grafts had comparable overall patency (57 vs 64%) and
      limb salvage (64 vs 75%) to more proximal tibial bypasses. Pedal bypass provides
      acceptable long-term outcomes for both patency and limb salvage. When forefoot
      ischemic tissue loss is present, pedal bypass, when feasible, appears preferable
      to peroneal bypass.

PMID- 7564317
TI  - Is measured energy expenditure correlated to injury severity score in major
      trauma patients?.
AB  - A common method for calculating energy needs (PEE) in acute trauma patients is
      multiplying the Harris-Benedict equation (BEE) by activity factors (AF) and
      variable stress factors (SF) depending on the injury severity. Selection of the
      SF can be an arbitrary and potentially inaccurate decision. The purposes of this
      study were: (1) to investigate the relationship between injury severity score
      (ISS) to postinjury energy expenditure (MEE), and (2) to compare the MEE to PEE
      when using the SF of 1.75. Thirty-five severely injured patients (mean ISS = 27.5
      +/- 10.7 SD) admitted to our Level I Trauma Center of the University of New
      Mexico were prospectively assessed for energy needs [PEE = BEE x 1.2(AF) x
      1.75(SF)] and ISS. Total nutritional support delivered estimated needs. Indirect
      calorimetry measurements were obtained on all of the patients within the first 7
      10 days following injury. No correlation (r = -0.042) existed between the MEE and
      ISS. There was a significant correlation (r = 0.772, P < 0.05) between PEE and
      MEE when using the SF of 1.75 for all of the patients. These results suggest that
      there is not a correlation between ISS and subsequent MEE in major trauma
      patients. In addition, using the SF of 1.75 will closely estimate energy needs in
      acute trauma patients.

PMID- 7564318
TI  - Regulation of the transcription factor C/EBP alpha following peritoneal sepsis.
AB  - The transcription factors C/EBP alpha and C/EBP beta belong to the leucine-zipper
      C/EBP (CCAAT/enhancer binding protein) family of DNA-binding proteins. C/EBP
      alpha and C/EBP beta are expressed in the liver and are implicated in the control
      of transcriptional events following following sepsis. It is hypothesized that
      inhibition of C/EBP alpha gene expression following sepsis may lead to some of
      the phenotypic features we recognize as sepsis syndrome such as decreased
      visceral protein (albumin) synthesis. In this study we demonstrate that C/EBP
      alpha mRNA accumulation is transiently inhibited 12 hr following peritoneal
      insult, consistent with previous data. However, we demonstrate that (1) there is
      increased binding of hepatic nuclear protein to the C/EBP alpha DNA response
      element 48 hr following insult, (2) a marked increase in C/EBP alpha protein is
      observed 48 hr following CLP insult compared with no increase in hepatic C/EBP
      alpha protein at 12 hr postinsult, (3) the increase in hepatic C/EBP alpha
      protein at 48 hr following cecal ligation and puncture is not associated with an
      increase in C/EBP alpha mRNA accumulation, (4) the increase in hepatic C/EBP
      alpha protein is associated with an increase in C/EBP beta protein, and (5)
      hepatic albumin mRNA accumulation is decreased at 12 and 48 hr following insult
      and does not correlate with the C/EBP alpha protein synthesis. We conclude that
      the possible role of the transcription factor C/EBP alpha with respect to
      decreased albumin gene expression following sepsis must be reevaluated.

PMID- 7564319
TI  - When does the lung die? Time course of high energy phosphate depletion and
      relationship to lung viability after "death".
AB  - The shortage of lung donors for clinical transplantation could be significantly
      alleviated if lungs could be retrieved from cadavers hours after death. However,
      the time course of loss of lung viability after circulatory arrest and organism
      death remains unclear. To determine postmortem adenine nucleotide tissue levels
      in the lung and their relationship to lung viability, Sprague-Dawley rats were
      sacrificed and then ventilated with 100% oxygen (n = 50, O2) or 100% nitrogen (n
      = 40, N2) or left nonventilated (n = 50). Lungs from control rats (n = 20) were
      retrieved immediately after sacrifice. Lungs in the three study groups were
      retrieved at successive intervals postmortem. Adenine nucleotides (ATP, ADP, and
      AMP) and hypoxanthine and xanthine metabolites of adenosine were extracted from
      lung tissue and measured using high-performance liquid chromatography. Pulmonary
      parenchymal cell viability was quantified by pulmonary artery infusion of trypan
      blue vital dye in the contralateral lung of each animal. By 4 hr postmortem,
      viability was 85 +/- 1% in the O2-ventilated cadaver rat lungs, significantly
      higher than in the N2-ventilated (43 +/- 8%) and in the nonventilated (48 +/- 4%)
      lungs, where the percentage of viable cells was similar. All of the groups showed
      a time-dependent decrement in ATP levels and total adenine nucleotide (TAN)
      levels after death, but this was markedly attenuated in O2-ventilated cadaveric
      rat lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564320
TI  - Effect of glutamine supplement and hepatectomy on DNA and protein synthesis in
      the remnant liver.
AB  - One of the physiological roles of glutamine is as a precursor for DNA synthesis.
      The aims of this study were to determine (1) whether glutamine-supplemented total
      parenteral nutrition (TPN) enhanced DNA and protein synthesis in the liver and
      (2) whether glutamine uptake was increased following partial hepatectomy in rats.
      Male Donryu rats (n = 59; body weight, 250-275 g) were randomized into four
      groups: (1) sham operation + standard TPN solution (C-STPN); (2) C + glutamine
      supplemented TPN (C-GTPN); (3) 70% partial hepatectomy + STPN (H-STPN); (4)
      partial hepatectomy + GTPN (H-GTPN). On Day 0, rats underwent either a sham
      operation or 70% partial hepatectomy and concomitantly were catheterized in the
      jugular vein. TPN was begun immediately after the surgery. GTPN was isocaloric
      and isonitrogenous with STPN and 25% of total nitrogen was given as glutamine. On
      Day 2, the animals were sacrificed after either a continuous infusion of 1-14C
      leucine or a bolus i.v. injection of bromodeoxyuridine. The rate of hepatic
      regeneration was enhanced with glutamine supplementation (H-STPN, 60.8 +/- 1.6%
      vs H-GTPN, 66.3 +/- 2.0, P < 0.05) due to an increase in protein synthesis in the
      liver (H-STPN, 134.0 +/- 10.3%/day vs H-GTPN, 160.9 +/- 6.9, P < 0.05) and DNA
      synthesis in hepatocytes (H-STPN, 23.1 +/- 2.5% vs H-GTPN, 31.4 +/- 2.9, P <
      0.05). The uptake of glutamine by the liver was increased following hepatectomy
      with GTPN supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564321
TI  - Nitric oxide as a positive inotropic agent in isolated rat hearts.
AB  - The purpose of this study was to examine the inotropic effects of nitroprusside
      (NP), a direct nitric oxide (NO) donor, in isolated rat hearts. Langendorff
      perfused hearts (n = 5), paced at 6 Hz, were subjected to 15 min of equilibration
      (EQ) followed by infusion of NP, producing a coronary artery concentration of 1 x
      10(-5) M. Coronary flow, left ventricular developed pressure (DP), end-diastolic
      pressure, and contractility and compliance (+/- dP/dt) were monitored throughout
      the experiment by a computerized data acquisition system. Myocardial oxygen
      consumption (MVO2) was measured at the end of EQ and after 2 1/2 min of NP
      infusion. Myocardial efficiency was calculated as the quotient of DP divided by
      MVO2. Values are expressed as the mean +/- SEM. Paired t tests were used to
      calculate statistical significance. Values for parameters monitored at end EQ and
      at 2 1/2 min NP infusion showed that there was a 93% increase in coronary flow,
      18, 17, and 16% increases in developed pressure, contractility, and compliance,
      respectively, no significant change in end-diastolic pressure, a 49% increase in
      myocardial oxygen consumption, and a 21% decline in myocardial efficiency (P <
      0.05 for all differences). We conclude that in the isolated rat heart, NO behaves
      as a positive inotrope.

PMID- 7564322
TI  - Quantifying c-myc expression in c-myc antisense phosphorothioate
      oligodeoxynucleotide-treated leukemic and colon cancer cell lines.
AB  - Antisense oligodeoxynucleotides (oligo) have been used to inhibit oncogene
      expression and have potential therapeutic applications. Using a 15-mer antisense
      phosphorothioate oligo (S-oligo), inhibition of c-myc oncogene expression and
      cellular proliferation is studied in two cell lines with c-myc overexpression: a
      colon cancer cell line (Colo 320 DM) and a promyelocytic leukemic cell line(HL
      60). Quantitative analysis of c-myc mRNA transcript is performed by competitive
      reverse transcription-polymerase chain reaction (RT-PCR). This utilizes an RNA
      competitive reference standard (CRS RNA) template that is identical to the native
      c-myc mRNA except for a short segment deletion to allow for differentiation of
      the two by gel electrophoresis. A fixed quantity of test mRNA and a series of
      known concentrations of CRS RNA template placed in the same test tubes under
      identical conditions are reverse transcribed and amplified by PCR. Since the
      reaction is competitive, the ratio of the PCR products reflects the ratio of the
      initial concentrations of the two templates. After gel electrophoresis, the two
      PCR products are quantified densitometrically. Treating Colo 320 DM and HL-60
      cells with c-myc antisense oligo and S-oligo results in a 20- to 100-fold
      decrease in c-myc mRNA transcripts, respectively. This inhibition is dose
      dependent and sequence specific (c-myc sense and missense oligo have no effects).
      The quantitative decrease in c-myc mRNA is associated with corresponding
      inhibition of c-myc oncoprotein synthesis as demonstrated by flow cytometry and
      Western blots. Furthermore, there is inhibition of cellular proliferation of the
      respective cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564324
TI  - Effector of hemodynamics during laparoscopy: CO2 absorption or intra-abdominal
      pressure?
AB  - Controversy has been raised about the effects of systemic carbon dioxide
      accumulation versus the intra-abdominal pressure on hemodynamics during
      laparoscopy. We compared the acid-base and hemodynamic changes during
      pneumoperitoneum in a randomized cross-over study between CO2 and nitrogen gases
      to test the hypothesis that the CO2 absorbed during laparoscopy, rather than the
      15 mmHg intra-abdominal pressure created, accounted for these changes. Eight
      adult pigs were anesthetized and ventilated with a fixed minute ventilation.
      Metabolic function was measured from analysis of expired flow by a metabolic
      measurement cart. After baseline periods, animals were randomized into two
      groups, for 2 hr of either CO2 or nitrogen pneumoperitoneum at 15 mmHg intra
      abdominal pressure, followed by 1 hr of recovery. After at least a 48-hr recovery
      period, the experiment was repeated with the other gas. Metabolic data revealed
      that there was a significant absorption of CO2 gas across the peritoneal
      epithelium during CO2 pneumoperitoneum. Animals insufflated with CO2 gas
      experienced a 75% increase in pulmonary CO2 excretion, with significant acidemia
      and hypercapnia, whereas there were no acid-base disturbances in those with
      nitrogen insufflation. Oxygen consumption remained essentially unchanged in both
      groups, even during pneumoperitoneum. CO2 pneumoperitoneum was also associated
      with systemic and pulmonary arterial hypertension and a reduction in stroke
      volume of up to 15%. Pneumoperitoneum alone did not compromise hemodynamics.
      Pneumoperitoneum using CO2 gas during laparoscopy resulted in systemic CO2
      absorption across the peritoneum. This led to acidemia, hypercapnea, and
      depressed hemodynamics. The intra-abdominal pressure routinely used during
      laparoscopic surgery did not affect metabolic function, acid-base balance, or
      hemodynamics in the experimental model.

PMID- 7564323
TI  - Increased efficacy of CSA following rearterialization in the rat OLTX model.
AB  - Many investigators presently use a rat orthotopic liver transplant (OLTX) model
      without rearterialization of the graft. Rearterialization has been demonstrated
      to have a variable effect on the rejection response in various strain
      combinations. However, there are little data on the effects in a model with
      immunosuppression. The influence of rearterialization on the efficacy of
      cyclosporine (CSA) in such a model was examined, with the hypothesis that
      rearterialization may alter the rejection response and efficacy of cyclosporine.
      OLTX was performed between adult male D Agouti rats and Lewis rats.
      Rearterialization was performed between the recipient and donor celiac axis, and
      CSA was delivered at 1 mg/kg/day by continuous infusion for 14 days
      postoperatively. Treatment groups consisted of no rearterialization/no CSA,
      rearterialization/no CSA, no rearterialization/CSA, and rearterialization/CSA.
      Survival time and histology of liver grafts were measured. Rearterialization
      itself did not prolong survival in this strain combination (median survival no
      rearterialization/no CSA is 11 days versus median survival rearterialization/no
      CSA is 10 days). The addition of CSA at this dose without rearterialization also
      did not prolong survival (median survival no rearterialization/CSA is 15.5 days).
      The combination of CSA with rearterialization did prolong survival significantly
      (median survival rearterialization/CSA is 22 days; P < 0.05 versus the other
      three groups). The mechanism of this increased efficacy is unknown, but may
      involve altered MHC antigen expression, altered metabolism of CSA, decreased
      toxicity of CSA, or decreased nonspecific inflammation in the rearterialized
      grafts.

PMID- 7564325
TI  - Impedance cardiography in the measurement of cardiac output: studies in rabbits.
AB  - A thoracic electric bioimpedance device with improved signal processing was used
      to noninvasively measure cardiac output in eight New Zealand White rabbits
      (average wt = 4.7 kg). Prospective correlation was performed between aortic
      thermodilution and impedance cardiography in a closed chest model. Aortic
      thermodilution was compared to the electromagnetic flowmeter in an open chest
      model. In four rabbits, the change in the impedance signal (dZ/dt) was quantified
      after repeated mechanical occlusion of the aorta and pulmonary artery. The mean
      cardiac output as measured by the impedance device was 0.56 +/- 0.01 liter/min
      (range 0.29-1.16 liter/min) compared to 0.53 +/- 0.01 liter/min (range 0.25-0.83
      liter/min) by aortic thermodilution. For the 116 data pairs, regression analysis
      revealed a statistically significant agreement (r = 0.82, P < 0.001) between the
      two techniques. The mean difference between the techniques (bias) was -0.03
      liter/min and 81% of the impedance values were within 0.1 liter/min of the
      individual thermodilution measurements. A statistically significant decline in
      the mean magnitude of the dZ/dt signal tracing (1.6 +/- 0.10 V-pre, 0.31 +/- 0.4
      V-post, P < 0.005, n = 21) was observed upon aortic arch occlusion. conversely,
      pulmonary artery occlusion did not have a statistical effect on the impedance
      signal (1.07 +/- 0.09-pre, 0.95 +/- 0.08-post, P > 0.05, n = 20). In conclusion,
      a significant correlation was observed between impedance cardiography and aortic
      thermodilution in measurement of cardiac output in sedated, anesthetized rabbits.
      This simple technique which involves application of skin electrodes may prove
      useful in measurement of cardiac output in surgical experimental small animal
      models.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564326
TI  - Nitric oxide participates in the hypotensive effect induced by adenosine A2
      subtype receptor stimulation.
AB  - In a previous study, we demonstrated that adenosine plays an important role in
      the central control of the cardiovascular system with involvement of adenosine A2
      rather than A1 subtype receptors. In the present study, we investigated the
      putative relationship between nitric oxide (NO) and adenosine in the central and
      peripheral control of the cardiovascular system. Adult male normotensive
      anesthetized rats were treated with N6-cyclohexyladenosine (CHA), an A1
      purinoceptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2
      purinoceptor agonist intracerebroventricularly (i.c.v. 3rd ventricle; 0.05-0.1
      0.5 microgram/rat) and by intravenous injection (0.5-1-5 microgram kg-1 i.v.).
      CPCA and CHA induced a significant and dose-dependent decrease in arterial blood
      pressure (BP). CHA effects were less marked than CPA. Rats were pretreated with
      xanthine amine congener (XAC), and A1 adenosine antagonist, with 3,7-dimethyl-1
      propargylxanthine (DMPX), an A2 adenosine antagonist (both administered at doses
      of 0.05 microgram/rat i.c.v. or 0.5 microgram kg-1 i.v.) and with N omega-nitro-L
      arginine methyl ester, an NO synthase inhibitor, (L-NAME, 90 microgram/rat i.c.v.
      and 0.3 mg kg-1 i.v.). The intracerebroventricular and intravenous pretreatment
      with DMPX or L-NAME inhibited CPCA-induced hypotension; the effect of L-NAME was
      weaker than that of DMPX. The L-NAME inhibitory effect was reversed both in the
      central nervous system (CNS) and at the peripheral level by pretreatment with L
      arginine (L-Arg; 90 mg kg-1 i.v.), a precursor of NO synthesis. Pretreatment with
      XAC, but not with L-NAME, reduced the hypotensive effect of CHA. Moreover,
      intracerebroventricular pretreatment with L-Arg (174 micrograms/rat) increased
      the hypotensive effect of CPCA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564327
TI  - Electrophysiological effects of SD-3212, a novel antiarrhythmic agent, on rabbit
      hearts in vivo and in vitro.
AB  - We examined the electrophysiological effects of SD-3212, a novel antiarrhythmic
      agent in rabbits in in vivo and in vitro experiments. During in vivo experiments,
      monophasic action potentials (MAPs) of the left ventricular endocardium were
      simultaneously recorded with surface ECG and arterial blood pressure (BP). Under
      constant atrial pacing, SD-3212 (0.1, 0.2, and 0.3 mg/kg/min) was continuously
      infused in rabbits for 20 min. SD-3212 > or = 0.2 mg/kg/min prolonged PQ
      interval, QRS duration, and MAP duration, and decreased arterial BP dose
      dependently. During in vitro experiments, transmembrane APs were recorded from
      the isolated papillary muscles by a microelectrode technique. SD-3212 (3 x 10(-6)
      10(-5) M) prolonged the AP duration (APD) and decreased the maximum upstroke
      velocity of the AP (Vmax) in a concentration-dependent manner without affecting
      the amplitude of AP or resting potential. The inhibitory action of SD-3212 on
      Vmax was enhanced as the stimulation frequency was increased, whereas the
      prolongation of APD did not vary with stimulation frequency. The results suggest
      that SD-3212 has an inhibitory action on some outward currents as well as sodium
      and calcium currents.

PMID- 7564329
TI  - A sensitive [Na,K]ATPase assay specific for inhibitors acting through the
      digitalis-binding site.
AB  - Efforts to study the endogenous sodium pump inhibitor (ESPI) have been
      complicated by the limited specificity of available assays. We recently developed
      an assay of [Na,K]ATPase inhibition more sensitive than conventional assays. This
      enhancement reflects a prereaction step that increases binding affinity of
      digitalislike molecules to the digitalis receptor. We tested the possibility that
      this enhanced inhibition is limited to inhibitors acting specifically through the
      digitalis-binding site. Using both the standard and sensitive [Na,K]ATPase
      methods, known specific inhibitors of the sodium pump (ouabain, digoxin, bufalin)
      showed significant increases in the inhibition in the sensitive as compared with
      the standard [Na,K]ATPase assay (ouabain 34.4 +/- 7.3 vs. 8.3 +/- 0.5%, digoxin
      43.2 +/- 9.1 vs. 7.2 +/- 3.1%, bufalin 46.9 +/- 5.0 vs. 22.6 +/- 1.6%). Some
      proposed candidates for the ESPI, acknowledged to be nonspecific inhibitors,
      showed no enhancement (oleic acid 36.0 +/- 4.5 vs. 34.8 +/- 5.6%,
      lysophosphatidyl choline 10.8 +/- 3.5 vs. 12.8 +/- 5.2%, and vanadate 34.3 +/-
      8.8 vs. 33.8 +/- 1.4%). Other candidates, whose inhibitory specificity is
      unknown, including an ESPI from the peritoneal dialysate of patients with renal
      failure were also studied. The ESPI showed enhanced inhibition (24.1 +/- 4.9 vs.
      5.3 +/- 2.0%). These studies suggest that the sensitive assay in conjunction with
      a standard [Na,K]ATPase assay may allow the early determination of candidates
      interacting specifically with the digitalis receptor to inhibit the sodium pump.

PMID- 7564328
TI  - Hemolysis on intravenous administration of a new calcium antagonist.
AB  - Hemolysis-inducing properties of the new calcium antagonist Ro 40-5967
      administered intravenously to 39 healthy male subjects were investigated in a
      placebo-controlled study. The volunteers were randomized into five parallel
      groups of 9 subjects each: three groups, receiving infusions of 40 mg Ro 40-5967
      in 60, 30, and 15 min, respectively; one group receiving 80 mg Ro 40-5967 in 30
      min as two simultaneous doses of 40 mg in the cubital veins of both arms; and one
      group receiving 80 mg Ro 40-5967 in 30 min in one arm. Within each group, 3
      subjects received placebo under randomized double-blind conditions. Plasma
      haptoglobin decreased by 67% after 3.5 h in 2 subjects who received 80 mg Ro 40
      5967 in one arm (treatment schedule thereupon discontinued). Serum bilirubin
      levels also increased in a dose-dependent manner in all groups as compared with
      placebo. Other parameters of hemolysis remained unchanged; no hemoglobinuria was
      observed. The intravascular hemolysis observed on infusion limits the therapeutic
      application of Ro 40-5967 to oral use only.

PMID- 7564330
TI  - Effect of palmitoyl carnitine isopropyl ester on the actions of BAY K 8644 and
      norepinephrine in the perfused rat heart.
AB  - We examined the actions of the isopropyl ester of palmitoyl carnitine (P1Pi), a
      novel vasodilator compound, on coronary constriction mediated by the calcium
      channel activator BAY K 8644 and positive inotropic responses mediated by
      norepinephrine (NE) and low sodium perfusion in perfused rat hearts. Langendorff
      perfused hearts were given bolus doses of BAY K 8644 or NE. The effects of P1Pi
      or atenolol on perfusion pressure, heart rate (HR), and developed tension changes
      induced by these agents were studied. In other experiments, low-sodium perfusion
      was used to manipulate sodium-calcium exchange in the presence and absence of
      P1Pi. P1Pi inhibited the coronary constrictor action of BAY K 8644 and also
      produced a selective inhibition of the inotropic but not the chronotropic action
      of NE. These effects of P1Pi were not associated with any depression of basal
      myocardial contractility. P1Pi did not affect the inotropic or coronary
      constrictor responses induced by low-sodium perfusion. The effects of P1Pi on the
      responses induced by BAY K 8644 and NE indicate that P1Pi inhibits activated L
      type calcium channels while having no effect on sodium-calcium exchange. These
      effects may be related to the charged nature of this amphiphilic compound.

PMID- 7564332
TI  - Effects of U-97018 on pressor responses to intracerebroventricularly administered
      angiotensin II in conscious normotensive rats.
AB  - We examined the effects of U-97018, an AT1 receptor antagonist, on the pressor
      response to intracerebroventricularly (i.c.v.) administered angiotensin II (AII)
      in conscious normotensive rats in comparison to losartan, EXP 3174, EXP 655, and
      saralasin. In an i.c.v. study, U-97018, losartan, and EXP 3174 reduced the
      pressor response. EXP 655, an AT2 selective antagonist, also inhibited the
      pressor response to i.c.v. AII. U-97018 combined with EXP 655 did not fully
      eliminate the pressor response to i.c.v. AII. Moreover, saralasin, a nonselective
      peptide AII antagonist, also failed to abolish the pressor response to i.c.v.
      AII. Therefore, both AT1- and AT2-receptors probably are functional in inhibiting
      the pressor response to i.c.v. AII and that a part of the i.c.v. AII-induced
      pressor response occurs through non-AT1- and non-AT2-receptors. In an intravenous
      (i.v.) study, U-97018, losartan, and EXP 3174 reduced the pressor response to
      i.c.v. AII. At 10 mg/kg orally (p.o.), which is an antihypertensive dose in
      spontaneously hypertensive rats (SHR), neither U-97018 nor losartan reduced the
      pressor response to i.c.v. AII even at 180 min after administration. This result
      indicates that neither U-97018 nor losartan, at the oral antihypertensive dose,
      reaches the brain in sufficient amount to affect the pressor response to i.c.v.
      AII.

PMID- 7564331
TI  - Novel 21-aminosteroidlike compounds prevent iron-induced free radical-mediated
      injury to vascular endothelial cells.
AB  - Free radicals appear to play a major role in the reperfusion injury of the
      myocardium. Iron chelators and antioxidants can prevent the reperfusion injury.
      The cellular source of free radicals during reperfusion is not clearly
      established. However, an important source may be the endothelial cells (EC). The
      protective effect of iron chelators and antioxidants on reperfusion injury of the
      myocardium may be partially mediated by their effect on vascular EC, which may
      attenuate the formation of hydroxyl radicals. We examined the protective effect
      of deferoxamine and antioxidants on iron-dependent free radical-mediated damage
      to EC and membrane lipid peroxidation and compared it with those of a new class
      of compounds (21-aminosteroids: U-74389F, U-74500A, U-78517F) which have both
      antioxidant and iron chelating properties. We examined viability of the EC and
      membrane lipid peroxidation using primary aortic EC. First, the effect of
      increasing iron concentration (0-3.8 microM) (added as ferric ammonium citrate)
      was characterized. We then examined the effect of deferoxamine (1-10 microM),
      butylated hydroxytoluene (BHT 1-10 mM), probucol (0.5-5.0 mM), allopurinol (1
      1,000 microM), U-74389F (2-20 microM), U-74500A (1-5 microM), and U-78517F (0.1
      1.0 microM) on reversing the effect of iron. With increasing iron concentration,
      there was a significant decrease in the viability of dog aortic or bovine
      pulmonary arterial EC as compared with NIH 3T3 or human fibroblasts. Equally,
      there was also a significant increase in lipid peroxidation of the cellular
      membranes. There were significant differences between the compounds with respect
      to their ability to maintain the viability of EC and prevent membrane lipid
      peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564333
TI  - Pharmacokinetics and pharmacodynamics of TP-9201, a GPIIbIIIa antagonist, in rats
      and dogs.
AB  - Because activation of the glycoprotein IIbIIIa (GPIIbIIIa) on platelets
      represents the final common pathway of platelet aggregation, inhibition of
      fibrinogen binding to the GPIIbIIIa complex provides an excellent target for
      inhibiting platelet aggregation. Peptides containing the arginine-glycine
      aspartic acid (RGD) sequence have been shown to inhibit the binding of fibrinogen
      to the GPIIbIIIa receptor on platelets competitively. We studied the
      pharmacokinetics of TP-9201, a synthetic cyclic peptide containing the RGD
      sequence, in rats and dogs after a 24-h intravenous (I.V.) infusion at three
      doses. The mean plasma clearance of TP-9201 after intravenous infusions of 30,
      150, and 600 mg/kg/day in rats was 20.2, 18.7, and 18.5 ml/min/kg, respectively.
      In beagles, TP-9201 clearance was 9.0, 7.5, and 7.3 ml/min/kg, corresponding to
      infusions of 10, 75, and 600 mg/kg/day, respectively. The volume of distribution
      was larger than plasma volume, and the terminal half-life (t1/2) was short in
      both species studied ranging from 0.5 to 0.7 h in rats and from 2.5 to 2.6 h in
      dogs. The results suggest that TP-9201 follows linear pharmacokinetics over the
      dose range studied. Despite the multiple blood sampling procedure used in the
      study, there were no hemorrhagic complications. Pharmacodynamic assessment in
      beagles showed that TP-9201 produces a dose-dependent inhibition of ADP-mediated
      platelet aggregation. The estimated in vivo IC50 value and sigmoidicity were 124
      and 3.5 ng/ml, respectively, suggesting that TP-9201 is a potent GPIIbIIIa
      antagonist with a steep concentration-effect relationship. TP-9201 is rapidly
      cleared from the circulation on termination of the intravenous infusion. There is
      a corresponding reversal of platelet inhibition as TP-9201 is cleared from the
      circulation.

PMID- 7564334
TI  - Effect of gamma 2-melanocyte-stimulating hormone on cerebral blood flow in rats.
AB  - The effects of the proopiomelanocortin-(POMC)-derived peptide gamma 2-melanocyte
      stimulating hormone (gamma 2-MSH) on mean arterial blood pressure (BP: MAP),
      heart rate (HR), internal and total carotid blood flow (BF) (CFint and CFtot,
      respectively), and regional cerebrocortical blood flow (CBF) were measured in
      urethane-anesthetized rats after intravenous (i.v.) and intracarotid (i.car.)
      administration of the peptide. gamma 2-MSH (1.5-100 nmol/kg) administered i.v.
      and i.car. caused a dose-dependent increase in MAP and HR. Injection of the
      peptide i.car. in the middose range resulted in a more pronounced pressor effect.
      Furthermore, the earlier onset of the hemodynamic effects after i.car. injection
      suggests that forebrain structures play a role in these effects. In addition to
      the pressor response, gamma 2-MSH produced a strong increase in CFint, CFtot, and
      CBF after both routes of administration, suggesting an increased intracerebral
      BF. Whereas the effects of the higher doses of gamma 2-MSH on MAP and CFtot were
      quantitatively comparable after either the intravenous or intracarotid
      administration, the effect on regional CBF and CFint was about twice as high
      after i.car. infusion, indicating a centrally mediated phenomenon underlying this
      effect on CBF. The increase in CFint cannot in itself be ascribed to a gamma 2
      MSH-mediated higher perfusion pressure (i.e., BP), since an equipressor dose of
      norepinephrine (NE) caused a significant decrease in CFint. The significant and
      more than twofold higher increase in CBF after intracarotid administration of
      gamma 2-MSH in comparison with administration of NE by the same route also
      suggests a central origin for the enhancement of microcirculatory flow due to the
      peptide.

PMID- 7564335
TI  - Differences in onset of impaired endothelial responses and in effects of vitamin
      E in the hypercholesterolemic rabbit carotid and renal arteries.
AB  - Hypercholesterolemia (HC) is known to be associated with impaired endothelium
      mediated responses in the vasculature. Evidence suggests that increased levels of
      reactive oxygen species (ROS) in the vessel wall may contribute to the impairment
      by decreasing the biological activity of endothelium-derived relaxing factor
      (EDRF). We compared the relative onset of HC-induced impairment of endothelial
      responses in the carotid and renal arteries and investigated the potentially
      beneficial effect of the antioxidant vitamin E. Rabbits were fed a 1% cholesterol
      enriched diet for 4 and 8 weeks, and vascular responses were compared using
      isolated ring segments of the carotid and renal arteries. In the carotid artery,
      relaxant responses to acetylcholine (ACh) were significantly and progressively
      impaired after 4 and 8 weeks; in the renal artery, however, responses were only
      slightly impaired after 8 weeks. There were no changes in responsiveness to
      A23187 or sodium nitroprusside (SNP) in either artery. We tested the effect of
      0.2% vitamin E by adding it to the diet for 4 weeks, after an initial 4-week of
      feeding of 1% cholesterol alone. Vitamin E reversed impaired responses to ACh in
      the carotid but not the renal artery and also enhanced relaxant responses to
      A23187. We conclude that the carotid artery is more susceptible than the renal
      artery to HC-induced endothelial impairment and that ROS may play a role in this
      impairment in the carotid artery but not in the renal artery.

PMID- 7564336
TI  - Effects of bradykinin on short-term variability in blood pressure and heart rate
      in rats: a spectral study.
AB  - Using a spectral procedure, we studied the effects of two treatment regimens of
      bradykinin (BK) on the blood pressure (BP) and heart rate (HR) variabilities in
      conscious Wistar rats. We performed a second series of experiments with
      hydralazine, at doses equihypotensive to those used in BK treatments, to
      discriminate between a specific effect of the peptide and those induced by
      vasodilation. We assessed the activity of the sympathetic nervous system (SNS),
      using the responses to atenolol and prazosin. First, at a subhypotensive
      treatment regimen, BK (5 micrograms/min) increased low-frequency (LF, 0.02-0.2
      Hz) and mid-frequency (MF, 0.2-0.6 Hz) frequency components of BP variability and
      also activated the SNS. Lesser enhancements of LF and MF areas were induced by
      hydralazine (0.15 mg/kg). Second, high-dose treatment regimens of BK (100
      micrograms/min) and hydralazine (2 mg/kg), which markedly decreased BP, did not
      change the areas of the LF and MF components of BP variability, whereas
      overactivity of the SNS was still assessed with the adrenergic blockers. On the
      other hand, high-dose BK induced a sixfold increase in the amplitude of the high
      frequency (HF, respiratory) component of BP. The effect of bradykinin on HF
      domain was associated with an increase in the depth of respiration in a group of
      anesthetized rats. Hoe 140 (60 micrograms/kg), a B-2 BK-receptor antagonist,
      abolished both the effects of BK on HF fluctuations in BP and the effects on
      breathing pattern. Our results demonstrate that BK induced different effects on
      LF and MF fluctuations in BP depending on the treatment regimen, whereas the SNS
      was activated by the two selected treatment regimens. Therefore, the MF component
      of BP variability should be considered only as a marker of the activity of the
      SNS when the BP level was not affected. Furthermore, we characterized an
      amplifying effect of BK on the HF domain of BP variability partly mediated by an
      increase in the depth of respiration.

PMID- 7564337
TI  - Beneficial effects of H290/51, a new lipid peroxidation inhibitor, on functional
      recovery after ischemia and reperfusion in isolated cold-arrested rat hearts.
AB  - Lipid peroxidation is one of the major mechanisms involved in free radical
      mediated postischemic myocardial injury. In the present study, a newly
      synthetized lipid peroxidation inhibitor H290/51 [cis-7methyl-9-methoxy
      5,5a,b,10b- tetrahydroindeno(2,1-6 indole)] was evaluated for its effects on
      myocardial functional recovery during reperfusion after 30-min global ischemia in
      isolated cold-arrested rat hearts. Administration of 200 and 800 nM H290/51 at
      initiation of global ischemia markedly improved the functional recovery, whereas
      50 nM H290/51 had no significant effects. The percent recovery of cardiac output
      (CO), left ventricular developed pressure (LVDP), and LVdP/dtmax at the end of
      the 30-min reperfusion period in the working mode was much higher in the groups
      receiving 200 and 800 nM H290/51 than that in vehicle group (CO 73 +/- 5 and 60
      +/- 5 vs. 23 +/- 7%; LVDP 79 +/- 5 and 73 +/- 8 vs. 43 +/- 10%; LV dP/dtmax 78 +/
      5 and 69 +/- 4 vs. 45 +/- 10%). The indenoindole compound H290/51 reduced
      ischemia/reperfusion-induced cardiac dysfunction.

PMID- 7564338
TI  - Cardiac hypertrophy in rats after intravenous administration of CI-959, a novel
      antiinflammatory compound: morphologic features and pharmacokinetic and
      pharmacodynamic mechanisms.
AB  - CI-959 is an antiallergic/antiinflammatory agent currently in development. In
      rats, daily bolus intravenous administration of CI-959 at doses > or = 10 mg/kg
      was associated with development of cardiac hypertrophy. There was no morphologic
      or biochemical evidence of myocyte injury, and cardiac hypertrophy rapidly
      reversed after treatment was discontinued. Cardiac hypertrophy was not evident
      when CI-959 was given orally or by continuous intravenous infusion with ALZA
      osmotic pumps. Maximum plasma drug concentrations (Cmax) were significantly
      higher when CI-959 was given by bolus intravenous injection, suggesting that
      cardiac effects were dependent on high Cmax concentrations. When neonatal rat
      cardiomyocytes were exposed to CI-959 in vitro, there was no evidence of myocyte
      enlargement or increased protein content. Cardiac hypertrophy was prevented by
      pretreatment with nonselective beta- and beta 1-selective adrenoceptor blockers
      as well as with central sympatholytics. beta 2- and alpha-adrenoceptor blockers
      were ineffective in preventing cardiac hypertrophy. Bolus intravenous CI-959
      administration resulted in prolonged hypotension and associated increase in
      plasma catecholamine levels, with apparent inhibition of reflex tachycardia. We
      conclude that CI-959-associated cardiac hypertrophy in rats was not a direct drug
      effect but instead was probably mediated by endogenous catecholaminergic
      stimulation of cardiac beta 1-adrenoceptors.

PMID- 7564339
TI  - Mechanism of acetylcholine-induced constriction enhanced by endothelial removal
      in isolated, perfused canine basilar arteries.
AB  - We examined the responses to intraluminally applied acetylcholine (ACh) in
      isolated and perfused canine basilar arteries by the stainless-steel cannula
      inserting method. In control vessels with intact endothelium, ACh produced a
      slight vasodilatation followed by a long-lasting vasoconstriction in the absence
      of induced tone. Propranolol, a beta-adrenoceptor blocker, had no effect on the
      response to ACh. After endothelial removal with intraluminal saponin, the
      constrictor component of the response to ACh was significantly enhanced, and the
      constrictions to prostaglandin F2 alpha (PGF2 alpha) and potassium chloride (KCl)
      were significantly potentiated. After exposure to extraluminal oxyhemoglobin, the
      ACh-induced constriction was significantly augmented, whereas the dilator
      component of the response to calcium ionophore A23187 was significantly
      attenuated. The enhanced constriction to ACh after endothelial removal was
      significantly blocked by OKY-046 (a thromboxane synthetase inhibitor) and
      nimodipine (a dihydropyridine calcium antagonist), but was slightly though not
      significantly suppressed by AA-861 (a lipoxygenase inhibitor). The response to
      PGF2 alpha was not altered by OKY-046 or AA-861. These results suggest that the
      potentiation of ACh-induced constriction after endothelial removal may be
      mediated in part by thromboxane A2 (TXA2), linked with extracellular calcium
      entry in smooth muscle cells (SMC). This mechanism might be involved in the
      pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH).

PMID- 7564340
TI  - Inhibition of restenosis by beraprost sodium (a prostaglandin I2 analogue) in the
      atherosclerotic rabbit artery after angioplasty.
AB  - We examined the effect of beraprost sodium (BPS), a stable prostaglandin I2
      (PGI2) analogue, on restenosis after balloon angioplasty in the atherosclerotic
      artery in rabbits. Regional atherosclerosis was induced in the femoral artery of
      New Zealand white rabbits by balloon deendothelialization and 2% cholesterol
      diet. After establishment of atheroma in the femoral artery, angioplasty was
      performed. In all, 65 rabbits were assigned to the following six subcutaneous
      drug treatment groups: control group (n = 13, saline 0.25 ml/kg); BPS low-dose
      group (n = 11, BPS 50 micrograms/kg twice daily); BPS high-dose group (n = 12,
      BPS 100 micrograms/kg twice daily); 2-day BPS high-dose group (n = 11, BPS 100
      micrograms/kg twice daily for 2 days after angioplasty); aspirin (ASA) group (n =
      10, ASA 30 mg once daily); and BPS+ASA group (n = 8, BPS 50 micrograms/kg twice
      daily plus ASA 30 mg once daily). Administration of each drug was started 30 min
      before balloon angioplasty and was continued until 4 weeks thereafter, except in
      the 2-day BPS high-dose group. Re-examination 4 weeks after the angioplasty
      showed significant (p < 0.05) preservation of the luminal diameter in the BPS
      high-dose and 2-day BPS high-dose groups (1.30 +/- 0.15 and 1.25 +/- 0.09 mm,
      respectively) as compared with that in the control group (0.83 +/- 0.10 mm);
      however, the luminal diameter in the BPS low-dose, ASA, and BPS+ASA groups (0.94
      +/- 0.18, 1.06 +/- 0.11, and 1.05 +/- 0.15 mm, respectively) was not
      significantly different from that in the control group.

PMID- 7564341
TI  - Kinetics of frequency-dependent conduction delay by class I antiarrhythmic drugs
      in human atrium.
AB  - We investigated use-dependent prolongation of interatrial conduction time (IACT)
      by class I antiarrhythmic drugs in 16 patients. Changes in IACT at the initiation
      of atrial pacing were used to evaluate the onset kinetics. We examined recovery
      kinetics by giving a single extra stimulus with a varying coupling interval after
      discontinuing train stimulation. Time constants of the onset kinetics were 1.52
      +/- 0.15/n(fast) and 0.087 +/- 0.031/n(slow) for mexiletine, 0.075 +/- 0.015/n
      for aprindine, 0.078 +/- 0.019/n for disopyramide, and 0.050 +/- 0.006/n for
      pilsicainide. The recovery time constants were 203 +/- 66 ms for mexiletine,
      1,021 +/- 162 ms for aprindine, 993 +/- 101 ms for disopyramide, and 2,930 +/-
      569 ms for pilsicainide. Class I antiarrhythmic drugs produced use-dependent IACT
      prolongation in humans, with characteristic kinetics for each agent similar to
      that of depression of the maximum upstroke velocity of cardiac action potential
      (Vmax) reported in in vitro studies.

PMID- 7564342
TI  - Impaired responsiveness of platelets from patients with stable angina pectoris to
      antiaggregating and cyclicAMP-elevating effects of prostaglandin E1.
AB  - The antiplatelet effects of prostacyclin (PGI2) and prostaglandin E1 (PGE1) are
      mediated by the same receptor and are secondary to intraplatelet cyclicAMP
      formation. Therefore, any dysfunction in PGI2/PGE1-stimulated cyclicAMP
      generation might lead to pathologically increased platelet aggregation. This
      possible consequence has not yet been studied. We examined antiaggregating
      effects of PGE1 in comparison with its cyclicAMP-elevating potency in platelets
      obtained from normal subjects and patients with stable angina pectoris; platelet
      hyperaggregability in such patients has been documented by us previously. ADP
      induced aggregation was measured in platelet-rich plasma (PRP); PGE1 was added to
      platelets 0.5 min after ADP for assessment of reversal of incipient aggregation.
      Concentrations of PGE1 associated with 50% reversal of aggregation (C50) were 2.4
      +/- 0.3 x 10(-8) M in normal subjects and 6.3 +/- 1.6 x 10(-7) M in patients (p <
      0.01). PGE1 produced a concentration-dependent increase in intraplatelet
      cyclicAMP, and there was a strong correlation between cyclicAMP-stimulating and
      antiaggregating effects of PGE1. Maximal increases in cyclicAMP with PGE1 10(-4)
      M were 330 +/- 10% for normal subjects and 220 +/- 20% for patients (p < 0.01).
      Thus, the observed decrease in PGE1-induced reversal of platelet aggregation in
      patients can be attributed to a suppressed cyclicAMP response to PGE1. These
      results are likely also to imply reduced platelet sensitivity in vivo to
      endogenous PGE1 and PGI2, which in turn might contribute to platelet
      hyperaggregability observed in cardiovascular diseases.

PMID- 7564343
TI  - Different actions between pindolol and propranolol on the ionic currents in
      spontaneously beating rabbit sino-atrial node cells.
AB  - Electrophysiological effects of beta-adrenoceptor blocking drugs (pindolol and
      propranolol) on the action potentials (APs) and the membrane currents in
      spontaneously beating rabbit sino-atrial (SA) node cells were examined by the two
      microelectrode voltage-clamp technique. Cumulative administrations of both
      blocking drugs (10(-7)-10(-6) M) prolonged the AP duration (APD) and caused a
      negative chronotropic effect in a concentration-dependent manner. Propranolol
      exhibited stronger responses than pindolol. At 10(-6) M, propranolol depolarized
      the maximum diastolic potential (MDP) and pindolol decreased the maximum rate of
      depolarization significantly, but the drugs had little or no effect on the AP
      amplitude (APA). In voltage-clamp experiments, both blockers (10(-7)-10(-6) M)
      inhibited the slow inward and the time-dependent outward currents in a
      concentration-dependent manner. Holding potential was -40 mV. The
      hyperpolarization-activated inward current was not affected by pindolol, but it
      was concentration-dependently inhibited by propranolol. The inactivation curve of
      Isi was not modified by either pindolol or propranolol. The activation curve of
      IK was unaffected by pindolol, but was shifted by propranolol 10(-6) M by
      approximately 11 mV in the depolarizing direction. These results indicate that
      both beta-adrenoceptor blocking drugs (pindolol and propranolol) inhibit the slow
      inward and the time-dependent outward currents, but produce different actions on
      the hyperpolarization-activated inward current and the activation kinetic of IK
      due to their pharmacological properties, thereby resulting in difference in
      decrease in the spontaneous activity of rabbit SA node cells.

PMID- 7564344
TI  - Effects of indapamide on atherosclerosis development in cholesterol-fed rabbits.
AB  - We examined the effect of indapamide (IND) on the development of atherosclerosis
      lesions in rabbits maintained on a 1% (wt/wt) cholesterol-enriched diet for a 16
      week period. IND was supplemented to the diet at three different levels to
      correspond to doses of 0.1, 0.3, and 1 mg/kg/day. Throughout the treatment,
      dietary consumption and body weight gains were comparable among the experimental
      and control groups. IND had no significant effect on plasma cholesterol,
      triglycerides, or phospholipids concentrations. Despite the lack of effect of the
      drug on these parameters, its administration produced a tendency toward a
      reduction in the aortic content of cholesterol and a dose-dependent and
      significant decrease in aortic damage. In the aortic arch, the extent of intimal
      aortic surface covered by grossly discernible atherosclerotic lesions was
      decreased by IND 1 mg/kg/day from 11.02 +/- 1.10 to 6.00 +/- 1.00% (p < 0.05) and
      from 9.72 +/- 1.39 to 5.37 +/- 1.20% (p < 0.05) in the remaining thoracic
      sections. In addition, the former dose also reduced the number of lesions per
      square centimeter from 3.69 +/- 0.68 to 1.72 +/- 0.53% (p < 0.05), and from 3.37
      +/- 0.85 to 1.55 +/- 0.46% (p < 0.05) in aortic arch and in thoracic sections,
      respectively. The possibility that IND reduces the development of atherosclerotic
      lesions produced by diet-induced hypercholesterolemia through a mechanism
      involving its calcium antagonist and/or its antioxidant activity is discussed.

PMID- 7564345
TI  - Nitric oxide synthase blockade and renal vascular responses to norepinephrine and
      endothelin-1 in conscious dogs.
AB  - The effects of inhibiting nitric oxide (NO) synthase with NG-nitro-L-arginine (L
      NNA) on renal vasoconstrictor responses to intrarenally administered
      norepinephrine (NE) and endothelin-1 (ET-1) were studied in conscious dogs. NE
      was infused into the renal artery at 0.02, 0.05, 0.1, and 0.2 micrograms/kg/min
      (15 min at each rate), with the dogs (n = 5) pretreated with either L-NNA 10
      mg/kg intravenously (i.v.) or vehicle (250 mM NaHCO3 solution at 2 ml/kg i.v.) NE
      produced dose-related decreases in renal blood flow (RBF) and renal vascular
      conductance that were significantly greater after L-NNA pretreatment than after
      vehicle. ET-1 was infused intrarenally at 2.7 ng/kg/min for 45 min with the dogs
      (n = 5) pretreated with either L-NNA 10 mg/kg i.v. or vehicle. ET-1 caused a
      progressive decrease in RBF and renal vascular conductance. In contrast to the
      results with NE, RBF and renal vascular conductance decreased significantly less
      in response to ET when the dogs were pretreated with L-NNA as compared with
      pretreatment with vehicle. Therefore, blockade of NO synthase augmented NE
      induced but not ET-induced renal vasoconstriction. The results therefore suggest
      that NO may act to lessen the renal vascular effects of NE, but this effect does
      not appear to be generalised to all vasoconstrictors.

PMID- 7564346
TI  - Comparison of the angiotensin II antagonist UP269-6 with the angiotensin
      converting enzyme inhibitor enalapril in normotensive volunteers challenged with
      angiotensin I.
AB  - We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II
      (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy
      male volunteers maintained on an unrestricted sodium intake and compared it with
      that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180
      mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double
      blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was
      given in an ascending dose order. The peak systolic blood pressure (SBP) response
      to a test dose of ANG I was determined serially before and after oral drug
      administration by monitoring finger BP by a photoplethysmographic method. No drug
      related side effect was observed. There was a dose-dependent inhibition of the
      SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking
      effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40
      mg doses of UP269-6, the SBP response was still attenuated when drug levels no
      longer were measurable in plasma. UP269-6 also produced a dose-related increase
      in active renin and ANG II levels at 24 h after drug intake. In these volunteers
      on unrestricted salt intake, no statistically significant effect on 24-h urinary
      aldosterone excretion was observed. Based on these preliminary data, the
      pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was
      estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally
      active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the
      ANG I pressor response as does enalapril 20 mg.

PMID- 7564347
TI  - Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril
      20 mg on blood pressure and neurohormonal effects in salt-deplete man.
AB  - We compared the response of the oral angiotensin II (Ang II) receptor antagonist
      (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril
      20 mg or placebo, during salt depletion in normal men. We also evaluated safety
      and tolerability. Sixteen healthy, normotensive male volunteers followed a
      standardised salt-depletion regimen for 3 days before each study day. Seven
      different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered
      double blind in a four-panel dose escalation, with enalapril and placebo
      randomised within each panel. Supine and erect blood pressure (BP) and heart rate
      (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and
      Ang II were measured at intervals. Urinary electrolytes and aldosterone were
      measured for the 24 h before dosing and for 24 h after dosing. Dizziness and
      light-headedness on standing were reported after UP 269-6 at higher doses.
      Enalapril caused one episode of symptomatic postural hypotension. No other drug
      related adverse events (AE) were noted. There was a dose-related decrease in
      supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40
      mg, with no change in HR. Based on the maximal decrease in mean arterial pressure
      (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril
      20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was
      greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary
      aldosterone suppression was greater with enalapril than with any dose of UP 269
      6.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564348
TI  - Acute thrombogenicity of arterial prostheses exposed to reduced blood flow in
      dogs: effects of heparin, aspirin, and prostacyclin.
AB  - Thrombogenesis is considered the principal cause of early failure of arterial
      grafts. Although antithrombotic drugs are recommended, their efficiency under low
      blood flow conditions is still being debated. In this study, we evaluated the
      ability of three drugs to modify the thrombotic properties of blood and,
      consequently, to influence platelet and fibrin deposition on the luminal surface
      of polyester arterial prostheses. In dogs receiving saline (control, n = 10),
      heparin (100 U/kg, n = 5), aspirin (325 mg, n = 5), or prostacyclin (15
      ng/kg/min, n = 5), a 30-cm, woven, loop-shaped, DeBakey arterial prosthesis was
      implanted as a substitute for the infrarenal aorta and exposed to reduced blood
      flow (50 ml/min) for 4 h. The parameters of the blood measured included activated
      clotting time (ACT) and platelet aggregation with collagen, determined before and
      after each treatment. Blood deposits were quantified using 111In labeled
      platelets and 125I-labeled fibrinogen. The ACT was significantly prolonged only
      after heparin treatment, and platelet aggregation, which was decreased by 35% (p
      < 0.05) after heparin treatment, was almost abolished after aspirin and
      prostacyclin treatments. As compared with the control group, both platelet and
      fibrin uptake on the luminal surface of the prostheses were reduced significantly
      by heparin by 87 and 37%, respectively. Despite their inhibition of platelet
      aggregation in vitro, aspirin and prostacyclin induced no significant change in
      platelet and fibrin deposition on the luminal surface of the woven polyester
      arterial prostheses under low blood flow conditions. Under such conditions,
      however, thrombin generation with subsequent platelet-fibrin deposition was
      prevented by use of heparin anticoagulant therapy.

PMID- 7564349
TI  - Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase in
      rats with hypertension.
AB  - Angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), are two
      mechanistically similar enzymes involved in the metabolism of several vasoactive
      peptides. Selective inhibitors of ACE are effective antihypertensive agents in
      high-renin, renovascular rats and normal-renin, spontaneously hypertensive rats
      (SHR), but are not effective in the low-renin, deoxycorticosterone acetate (DOCA)
      salt hypertensive rats. In contrast, NEP inhibitors are only effective in the low
      renin model of hypertension. Treatment with a combination of selective inhibitors
      or with a dual inhibitor of both enzymes produces an antihypertensive response
      regardless of basal plasma renin activity. In this study, we compared the
      activities of MDL 100,173, a novel subnanomolar inhibitor of both ACE and NEP,
      with those of equimolar doses of captopril, a selective ACE inhibitor, following
      intravenous administration in these three rat models of hypertension. Treatment
      with MDL 100,173 significantly lowered blood pressure compared to vehicle
      treatment in all three models, whereas captopril treatment lowered blood pressure
      in the renovascular and SHR models only. Administration of MDL 100,173 also
      significantly elevated diuresis and natriuresis compared to either vehicle or
      captopril treatment in the SHR and DOCA-salt rats. Urinary excretion of atrial
      natriuretic peptide (ANP) was increased by MDL 100,173 treatment in all three
      models of hypertension. Treatment with captopril did not alter urine, sodium, or
      ANP excretion in any of the models. However, plasma-renin activity was elevated
      by both MDL 100,173 and captopril
      '''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''' ''''''''

PMID- 7564350
TI  - Controlled multicenter study with quinapril, hydrochlorothiazide, and combination
      in patients with moderate to severe hypertension.
AB  - In an 8-week, double-blind, randomized, active-controlled, multicenter study with
      three parallel treatment groups, we compared the efficacy and safety of once
      daily 20 mg quinapril plus 12.5 mg hydrochlorothiazide (HCTZ) with each drug as
      monotherapy in patients with moderate to severe hypertension. Hypertensive out
      patients with supine diastolic blood pressure (DBP) > or = 105 and < or = 120 mm
      Hg at the end of a 2- to 4-week placebo-baseline period were randomly assigned to
      one of the treatment groups. Of the 323 patients who were randomized to double
      blind medication, 297 completed the study, but 6 patients were excluded for
      violations of protocol; therefore, statistical analysis was performed in 291
      patients. Only 7 patients withdrew owing to lack of efficacy (2 receiving
      combination therapy). In all three treatment groups, clinically significant
      reductions in DBP were achieved. Combination therapy was statistically more
      effective than each component in both evaluable data and intent-to-treat
      analyses. The incidence of adverse events (AE) was 24% in the quinapril
      monotherapy group, 14% in the combination therapy group, and 11% in the HCTZ
      monotherapy group. Orthostatic hypotension with related symptoms was observed in
      4 patients (2 receiving quinapril monotherapy, 1 receiving HCTZ monotherapy, and
      1 receiving combination therapy). Once-daily quinapril plus HCTZ provided
      increased reduction of DBP as compared with the monotherapies and was well
      tolerated in patients with moderate to severe hypertension.

PMID- 7564351
TI  - Endothelial nucleotide-mediated aorta relaxation in aged Watanabe heritable
      hyperlipidemic rabbits.
AB  - We investigated the activity of muscarinic and purinergic endothelial receptors
      during atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbit aorta.
      Experiments were performed on isolated thoracic aorta from WHHL rabbits aged 1
      and 2.5 years. The relaxant response to acetylcholine (ACh) was progressively
      reduced with aging, being almost completely abolished in 2.5-year-old rabbits.
      The relaxant effect of ATP was not affected by the P2-purinoceptor antagonist
      suramin, thus excluding any involvement of relaxant P2y purinoceptors in both
      considered ages. The pyrimidine UTP, acting on nucleotide (P2U) receptors,
      produced concentration-dependent relaxation in 1-year-old WHHL rabbit aorta only
      in the presence of endothelium; relaxation was reduced in older animals. In 1
      year-old WHHL rabbits, the endothelium-dependent relaxant effect of UTP was not
      antagonized by suramin, but was by the inhibitors of nitric oxide (NO) effect,
      methylene blue (MB) and L-NG-nitroarginine methyl ester (L-NAME), suggesting
      involvement of NO in the UTP-mediated relaxation. Morphological data from
      electron microscopy observations indicated the presence of typical
      atherosclerotic lesions and extensive dystrophic changes in endothelial cells,
      gradually evolving at 1 and 2.5 years of age. The present data suggest that
      progressive atherosclerosis differentially affects the activity of endothelial
      receptors: The most precociously altered is the P2y-purinoceptor, followed by an
      impairment of the muscarinic and finally of the P2U-purinoceptor.

PMID- 7564352
TI  - Differential effects of a missed dose of trandolapril and enalapril on blood
      pressure control in hypertensive patients.
AB  - A double blind randomised comparison of two angiotensin-converting enzyme (ACE)
      inhibitors was made in a study in which ambulatory blood pressure was monitored
      over a steady-state dosage interval and the subsequent 24-h period, the latter
      being designed to mimic a missed dose of drug. The blood pressure responses on
      active therapy were compared to an identical recording made at the end of a 3
      week placebo run in period. Eighty-eight essential hypertensives were treated
      with a morning dose of either trandolapril 2 mg or enalapril 20 mg. Mean systolic
      (SBP) and diastolic blood pressure (DBP) were calculated on each of the following
      periods: daytime (8:31 a.m.-10:30 p.m.), nighttime (10:31 p.m.-6:30 a.m.), and
      early morning (6:31 a.m.-8:30 a.m.). Trough/peak was calculated for each group
      both on active treatment and after a missed dose. Twelve patients were excluded
      from analysis before opening the randomisation code because of inadequate
      ambulatory blood pressure monitoring (ABPM) recordings. Demographic data, placebo
      period office blood pressure, and ABPM recordings were not significantly
      different between the two groups. Both trandolapril and enalapril effectively
      reduced blood pressure over the 24-h period. Twenty four-hour ambulatory SBP and
      DBP decreased from 148 +/- 14/92 +/- 10 mm Hg to 135 +/- 14/83 +/- 10 mm Hg in
      the trandolapril group (p < 0.001). The same parameters decreased to a quite
      similar extent after enalapril, from 143 +/- 13/91 +/- 5 mm Hg to 133 +/- 15/83
      +/- 8 mm Hg (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564353
TI  - Effect of thromboxane A2 antagonist GR32191B on prostanoid and nonprostanoid
      receptors in the human internal mammary artery.
AB  - Arterial grafts have been demonstrated to be very effective for coronary artery
      bypass surgery. Thromboxane A2 (TXA2) is a potent vasoconstrictor for arterial
      grafts. To determine whether the specific TXA2 (TP) receptor antagonist GR32191B
      is effective in inhibition of prostanoid or nonprostanoid receptors, we studied
      the effect of GR32191B in human internal mammary artery (IMA) segments, taken
      from coronary bypass patients, in organ chambers. In IMA precontracted with
      U46619 (10 nM, n = 7), prostaglandin F2 alpha (PGF2 alpha 1 microM, n = 7), or
      potassium chloride (K+ 25 microM, n = 6). GR32191B induced 100.0 +/- 0, 97.86 +/-
      2.14, or 45.87 +/- 7.63% relaxation. In other experiments, one IMA ring taken
      from each patient was used as a control and others from the same patient were
      allocated to other groups treated with different concentrations of GR32191B [3
      300 nM for U46619, 30 nM-3 microM for PGF2 alpha, 300 nM-100 microM for K+, 3
      microM norepinephrine (NE), and 3 microM for 5-hydroxytryptamine (5-HT)] for 1 h
      before concentration-contraction curves to these vasoconstrictors (expressed as
      percentage of K(+)-induced contraction force) were established. Treatment with
      GR32191B (300 nM) significantly decreased the contraction induced by U46619 (from
      306.4 +/- 22.1 to 61.9 +/- 24.9%, p < 0.01) and that induced by PGF2 alpha (from
      208.2 +/- 13.5 to 1.4 +/- 1.4%, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564355
TI  - The effects of losartan and captopril on vasopressor actions of cirazoline in the
      absence and presence of SZL-49 and nifedipine.
AB  - The effects of the nonpeptide angiotensin II receptor antagonist losartan and the
      angiotensin-converting enzyme inhibitor captopril on pressor responses to the
      selective alpha 1-adrenoceptor agonist cirazoline (10 ng/kg-3.0 mg/kg) in the
      pithed rat were compared. In addition, the effects of losartan and captopril on
      pressor responses to cirazoline were compared in the presence of the selective
      irreversible alpha 1-adrenoceptor antagonist SZL-49 (1-(4-amino-6,7-dimethoxy-2
      quinazolinyl)-4-(2-bicyclo[2,2,2]octa-2,5- dienyl-carbonyl)-piperzine) and/or the
      Ca2+ channel antagonist nifedipine. Losartan (5.0 mg/kg) and captopril (3.0
      mg/kg), as compared to saline, significantly lowered the blood pressure of
      intact, anaesthetized and pithed rats. Continuous infusion with vasopressin was
      used to restore the blood pressure of pithed rats pretreated with losartan or
      captopril to a level comparable to animals that had received saline. Losartan,
      captopril, nifedipine (1.0 mg/kg), and SZL-49 (10.0 mg/kg) antagonized the
      pressor actions of cirazoline, which displaced the dose-diastolic blood pressure
      response curve for the agonist to the right. Moreover, pressor responses to
      cirazoline were significantly reduced in rats that had received losartan and
      nifedipine in comparison to nifedipine alone. In contrast, in rats treated with
      nifedipine, further administration of captopril did not significantly reduce
      pressor responses to cirazoline as compared to nifedipine alone. Cirazoline
      mediated pressor responses at all doses were significantly attenuated in rats
      treated with SZL-49 and either losartan or nifedipine combined as compared to SZL
      49 alone. In contrast, only cirazoline-mediated pressor responses at lower doses
      were significantly reduced by pretreatment with a combination of SZL-49 and
      captopril as compared to SZL-49 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564354
TI  - Antifibrillary action of class I-IV antiarrhythmic agents in the model of
      ventricular fibrillation threshold of anesthetized guinea pigs.
AB  - We compared the effects of class I-IV antiarrhythmic agents on the ventricular
      fibrillation threshold (VFT) induced by electrical stimulation directly on the
      myocardium in anesthetized, open-chest guinea pigs. VFT was assessed by
      determining the intensity (mA) of electrical current required to induce
      ventricular fibrillation (VF) and is expressed as a percentage change of the
      baseline premedication value. The following antiarrhythmic agents or their
      solvent were administered intravenously (i.v.) to pentobarbital-anesthetized
      animals (n = 6-12 per group): class I antiarrhythmic agent encainide (1.5 mg/kg);
      class II antiarrhythmic agents atenolol (2.5 mg/kg), metoprolol (2.5 mg/kg), and
      nebivolol (2.5 mg/kg); class III antiarrhythmic agents dofetilide (0.08 mg/kg),
      terikalant (0.04 mg/kg), and DL-sotalolol (10 mg/kg); and class IV antiarrhythmic
      agent verapamil (0.16 mg/kg). The antiarrhythmic compounds or their solvents
      resulted in the following changes in the VFT at 15 min after treatment: saline
      control, 1 +/- 14% (mean +/- SEM) from its baseline value; 10% hydroxypropyl-beta
      cyclodextrine (CD), 4 +/- 13%; encainide, 183 +/- 46% (p < 0.05 vs. saline);
      atenolol, 66 +/- 23% (p > 0.05 vs. saline); metoprolol, 89 +/- 25% (p > 0.05 vs.
      saline); nebivolol, 224 +/- 58% (p < 0.05 vs. 10% CD); DL-sotalol, 485 +/- 119%
      (p < 0.05 vs. saline); dofetilide, 357 +/- 69% (p < 0.05 vs. saline); terikalant,
      487 +/- 183% (p < 0.05 vs. saline), and verapamil, -17 +/- 21% (p > 0.05 vs.
      saline). At the doses used, all compounds significantly reduced heart rate
      (HR).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564356
TI  - Cardioprotection with the KATP opener cromakalim is not correlated with ischemic
      myocardial action potential duration.
AB  - We endeavored to determine if the enhanced shortening of the myocardial action
      potential duration (APD) during ischemia can be dissociated from the
      cardioprotective effects of the adenosine triphosphate (ATP) sensitive potassium
      channel (KATP) opener cromakalim. To establish if there is a relationship between
      APD shortening and the cardioprotective effect of cromakalim, we determined the
      effect of a dose of the delayed rectifier (IKr) blocker dofetilide (which
      abolishes the APD shortening effect of cromakalim) on the cardioprotective
      activity of cromakalim. Cromakalim was infused at a previously determined
      cardioprotective dose (10 micrograms/kg + 0.3 micrograms/kg/min infusion i.c.),
      and we determined the effect of 1 mg/kg (followed by a 0.01 mg/kg/min i.v.
      infusion) dofetilide alone and in combination with cromakalim on APD shortening
      and infarct size (90-min coronary occlusion and 5-h reperfusion) in anesthetized
      dogs. Dofetilide completely abolished the APD shortening effects of cromakalim
      during ischemia such that APD was similar to preischemic values. Cromakalim only
      shortened the APD during ischemia, although this effect was attenuated late into
      ischemia. Cromakalim significantly reduced infarct size (40% reduction from
      vehicle group value), whereas dofetilide alone had no effect. Dofetilide, at a
      dose that prevented the cromakalim-induced shortening of APD in ischemic tissue,
      did not attenuate the cardioprotective effects of cromakalim. No differences in
      collateral blood flow for any of the groups were observed. Dofetilide did cause a
      slight bradycardia, but this effect is unlikely to affect the interpretation of
      the results. These data suggest that APD shortening observed with the KATP opener
      cromakalim is not correlated with its cardioprotective effects.

PMID- 7564357
TI  - Role of tyrosine kinases in norepinephrine-induced contraction of vascular smooth
      muscle.
AB  - We used various probes to examine the involvement of tyrosine kinases in
      norepinephrine (NE)-induced contractile responses of the isolated rat aorta
      denuded of endothelium. The putative tyrosine kinase inhibitors, genistein and
      tyrphostin, significantly inhibited the contractile responses of the aorta to NE
      but not to potassium chloride (KCl). The protein tyrosine phosphatase inhibitor,
      sodium orthovanadate, also selectively potentiated the contractile response of
      the artery to NE. The inhibitory effect of genistein on NE-induced contraction
      was observed both in the absence and presence of extracellular calcium, which
      produced phasic and tonic contractile responses, respectively. The effect of
      genistein was more pronounced on the phasic contraction, suggesting that tyrosine
      kinases play a greater role in mediating the responses associated with the
      release of intracellular calcium. Genistein, however, had no effect on
      contraction elicited by the direct protein kinase C (PKC) activator phorbol 12,
      13 dibutyrate (PDB), providing evidence for the lack of involvement of tyrosine
      kinases in PKC-mediated contractile responses which contribute to the NE-induced
      tonic contraction. In contrast, genistein attenuated the contraction of the
      vessel evoked by the direct G-protein activator sodium fluoride (NaF), suggesting
      the involvement of tyrosine kinases in responses associated with G-protein
      activation. The data indicate that genistein- and tyrphostin-sensitive tyrosine
      kinases participate in NE-induced contraction of rat aortic smooth muscle.
      Although this may involve one or more steps in the signal transduction pathway,
      the enzymes appear to have a greater role in mediating the responses linked to
      the release of intracellular calcium and have no roles in certain other
      processes, including those mediated by PKC activation.

PMID- 7564358
TI  - Electrophysiological demonstration and activation of mu-opioid receptors in the
      rabbit sinoatrial node.
AB  - To investigate the presence of opioid receptors and their physiological role in
      cardiac pacemaker cells, we studied electrophysiological effects of fentanyl
      citrate, an activator of the mu-opioid receptors, on the spontaneous action
      potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1
      mm) of rabbit sinoatrial (SA) node (SAN). Fentanyl (0.1-3 microM) progressively
      decreased the AP amplitude (APA), maximal rate of depolarization (MRD), and
      spontaneous firing frequency (SFF) and prolonged the AP duration (APD) and
      diastolic interval in a concentration-dependent manner. At 1 microM, the
      spontaneous activity ceased in two of the eight preparations. These actions were
      blocked by a mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but
      were not modified by either kappa-opioid receptor antagonist nor-binaltorphimine
      (nor-BNI), or delta-opioid receptor antagonist ICI-174864. In voltage-clamp
      experiments using double microelectrode techniques, 1 microM fentanyl reduced the
      Ca2+ current (ICa) obtained on step depolarization from -40 to 0 mV by 19.9 +/-
      9.3% (p < 0.05, n = 5), the fast and slow components of the delayed rectifying K+
      current (IKfast, IKslow) tail obtained on repolarization from 10 to -60 mV by
      54.7 +/- 4.7 and 41.4 +/- 2.4% (p < 0.05, n = 4), and the hyperpolarization
      activated inward current at -90 mV by 12.6 +/- 0.5% (p < 0.05, n = 7),
      respectively. The gating kinetics of ICa and IKslow were not altered.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564359
TI  - Effects of dicentrine on the mechanical properties of systemic arterial trees in
      dogs.
AB  - We evaluated the effects of dicentrine on the physical properties of systemic
      arterial trees. Dicentrine, isolated from Lindera megaphylla, was identified as a
      potent, selective alpha 1-adrenoceptor antagonist. We used high-fidelity
      multisensor catheter to measure the ascending aortic pressure and flow signals in
      9 mongrel dogs. A succinct T-tube model with vascular nonuniformity was adopted
      to relate the pulsatile pressure and flow waves. The model-estimated parameters
      were capable of representing the mechanical properties of the blood vessel walls.
      Dicentrine had a beneficial effect on the rigidity of head and body circulation,
      respectively. There were great improvements not only in the tube distensibility
      and wave transmission time, but also in the peripheral load compliance and
      resistance. In global circulation that was defined as the parallel combination of
      head and body circulation, dicentrine significantly reduced values in
      characteristic impedance of the ascending aorta from 164 +/- 67 to 105 +/- 43
      dynes/s/cm5, and in wave reflection factor from 0.46 +/- 0.14 to 0.36 +/- 0.13,
      and in total peripheral vascular resistance from 4,751 +/- 1,226 to 3,581 +/-
      1,277 dynes/s/cm5. On the other hand, total peripheral load compliance was
      increased from 0.2950 +/- 0.1794 to 0.4457 +/- 0.2199 ml/mm Hg. Cardiac output
      (CO) and heart rate (HR) remained unchanged, however. Dicentrine had an impact on
      the mechanical properties of Windkessel vessels and resistance vessels in the
      systemic circulation.

PMID- 7564360
TI  - Age-dependent changes in the beta-adrenoceptor-G-protein(s)-adenylyl cyclase
      system in human right atrium.
AB  - With increasing age, cardiac beta-adrenoceptor function decreases. To study
      possible mechanisms underlying this process, we assessed in right atrial
      appendages from 52 patients of different ages (group A, < 20 years, mean age 3.7
      +/- 1.0 years, n = 20; group B, 20-50 years, mean age, 37.9 +/- 2.3 years, n = 9;
      group C, > 50 years, mean age 66.1 +/- 1.5 years, n = 23) without apparent heart
      failure who were undergoing open heart surgery beta-adrenoceptor number and
      subtype distribution (by (-)-[125I]-iodocyanopindolol [ICYP] binding), adenylyl
      cyclase activity, and Gs- and Gi-protein alpha-subunits (by quantitative Western
      blotting). beta-Adrenoceptor number in the three groups was not significantly
      different; in contrast, basal, 10 microM GTP-, 100 microM isoprenaline (ISO), 10
      mM NaF-, 100 microM forskolin-, and 10 mM Mn(2+)-stimulated adenylyl cyclase
      activity was significantly higher in group A than in group B and was further
      decreased in group C. Similarly, 100 microM terbutaline-, 100 microM histamine-,
      and 100 microM 5-HT-stimulated adenylyl cyclase activity significantly decreased
      from group A to group C. Moreover, all these adenylyl cyclase parameters were
      significantly negatively correlated with the age of the patients. Although Gs
      alpha was not altered, Gi alpha in group C was significantly higher than in group
      A; moreover, there was a weak but significant positive correlation between Gi
      alpha and the age of the patients. We conclude that an impairment of the activity
      of the catalytic unit of adenylyl cyclase is involved in the decrease in cardiac
      beta-adrenoceptor function with age; an increase in Gi alpha might contribute
      further to the reduced beta-adrenoceptor function.

PMID- 7564361
TI  - Effects of idrapril calcium on tissue angiotensin-converting enzyme in rats.
AB  - Tissue angiotensin-converting enzyme (ACE) inhibition was measured in rats after
      single intravenous (i.v.) and oral (p.o.) doses of idrapril calcium, and the
      correlation between peak inhibition and tissue concentration of the drug was
      investigated. Five minutes after idrapril calcium (3 mg/kg i.v. as free acid),
      ACE in the examined tissues (serum, lungs, kidneys, heart, aorta, adrenals,
      testes, and brain) showed > 50% inhibition, always associated with measurable
      amounts of idrapril. After 90 min, ACE activity was still inhibited only in
      serum, lungs, kidneys, and aorta, recovering to basal values by 8 h in all
      samples but serum. Oral idrapril calcium (30 mg/kg) produced > 50% peak ACE
      inhibition in serum, lungs, and kidneys, in which measurable levels of the drug
      were detected, and in the aorta, where idrapril was not detected. Other tissues
      showed neither marked inhibition nor measurable drug levels. Kinetics of ACE
      inhibition in affected tissue mirrored those observed after intravenous
      administration. Idrapril, despite its hydrophilic nature, is able to reach
      extravascular tissues and to inhibit local ACE. However, in no tissue did the
      effect on ACE last longer than in serum and the hypothesis of a peculiar role of
      tissue RAS in determining the hypotensive activity of idrapril calcium is not
      supported in rats.

PMID- 7564362
TI  - Double-blind comparison of antihypertensive treatment with ramipril and
      piretanide, given alone or in combination.
AB  - In a double-blind, randomized, multicenter trial, we compared the efficacy and
      safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the
      respective component monotherapies in hypertensive patients [supine diastolic
      blood pressure (DBP) 100-114 mm Hg]. After a single-blind run-in period on
      placebo, 611 patients were randomized to ramipril (n = 209), piretanide (n =
      201), or the combination therapy (n = 201). At randomization, the three groups
      had the same characteristics (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/-
      6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with
      monotherapy. As compared with piretanide monotherapy, the gain in the
      antihypertensive effect in the supine position averaged 2.1 mm Hg [90% confidence
      interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SBP) and 1.9 mm Hg (CI 0.3
      3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, these
      differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008) and 2.0 mm Hg (CI 0.5
      3.6 mm Hg, p = 0.009). The incidence of adverse events (AE) and the changes in
      biochemical measurements were similar in the three treatment groups with the
      exception of spontaneously reported polyuria and serum uric acid concentration.
      Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n =
      23) and combined therapy (n = 19) than with ramipril therapy (n = 1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564363
TI  - Renal and systemic effects of the renin inhibitor remikiren in patients with
      essential hypertension.
AB  - Remikiren is an orally available renin inhibitor with an established blood
      pressure-lowering effect in patients with essential hypertension. No data are
      available on the renal effects of remikiren in humans. We therefore studied the
      effects of a single oral administration of remikiren on blood pressure and renal
      function in 16 patients with essential hypertension on a restricted dietary
      sodium intake. Remikiren induced a peak fall in mean arterial pressure of 8.5 +/-
      0.8%. The glomerular filtration rate (GFR) remained stable, whereas the effective
      renal-plasma flow rose by 11.3 +/- 1.4%. As a consequence, the filtration
      fraction and the renal vascular resistance fell by 11.7 +/- 1.2% and 17.6 +/-
      1.3%, respectively. These systemic and renal hemodynamic changes were more
      pronounced in individuals with a higher initial immunoreactive renin. Remikiren
      induced a significant rise in the fractional excretion of sodium [0.38% (0.24
      0.52) to 0.50% (0.31-0.76)] and lithium [28.7% (25.0-32.4) to 33.2% (27-39.4)].
      Moreover, remikiren induced a decrease in urinary albumin excretion [497 (268
      815) to 252 (114-389) micrograms/h]. In patients with essential hypertension, a
      single oral dose of remikiren can induce a renal vasodilation, without affecting
      the GFR and despite a significant decrease in blood pressure. This systemic and
      renal hemodynamic response is more pronounced in case of a more activated renin
      angiotensin system.

PMID- 7564364
TI  - Electromechanical effects of zatebradine on isolated guinea pig cardiac
      preparations.
AB  - The effects of zatebradine on rate and contractile force and transmembrane action
      potentials were studied in isolated guinea pig atria and ventricular papillary
      muscles. In spontaneously beating right atria, zatebradine, 10(-7)-10(-4) M,
      produced a negative chronotropic effect (IC50 = 6.5 +/- 3.0 x 10(-6) M) and
      prolonged the recovery of the sinus function. In addition, it produced a biphasic
      effect on the atrial contractility, so that at concentrations up to 10(-5) M, it
      exerted a positive inotropic effect, whereas at higher concentrations, a negative
      inotropic effect was observed (IC50 = 9.0 +/- 0.3 x 10(-5) M). In electrically
      driven left atria, zatebradine produced a negative inotropic effect, though no
      changes were observed in the total contraction time or the time to peak tension.
      In papillary muscles, zatebradine > or = 5 x 10(-6) M caused a significant
      decrease in the maximum upstroke velocity (Vmax) without altering the resting
      membrane potential and exerted biphasic effects on the action potential duration
      (APD). At concentrations up to 5 x 10(-5) M, it prolonged the APD, whereas at
      higher concentrations, it shortened the APD. In addition, zatebradine, 10(-4) M,
      significantly reduced the amplitude and Vmax of the slow action potentials
      elicited by isoproterenol in K(+)-depolarized papillary fibres. In the presence
      of zatebradine, trains of stimuli at rates between 0.5 and 3 Hz led to an
      exponential decline in Vmax (frequency-dependent Vmax block), which was augmented
      at higher rates of stimulation. The time constant for the recovery of Vmax from
      the frequency-dependent block was 2.9 s.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564365
TI  - Relative contribution of alpha 1-adrenoceptor blocking activity to the
      hypotensive effect of the novel calcium antagonist monatepil.
AB  - Monatepil, a novel calcium antagonist, has alpha 1-adrenoceptor blocking
      activity; in the present study, we examined the relative contribution of this
      alpha 1-blocking activity to its hypotensive effect. Monatepil and diltiazem
      produced dose-dependent hypotensive effects in anesthetized rats with the same
      potency. Prazosin and monatepil inhibited the L-phenylephrine (L-PE)-induced
      pressor response, whereas diltiazem scarcely did. The injection of prazosin
      produced a decrease in blood pressure (BP) in anesthetized rats. The decrease was
      recovered with angiotensin II (AII) infusion in a dose-dependent manner. We
      developed a new rat model by first intravenously injecting prazosin and then
      infusing AII in anesthetized rats. In this model, diltiazem produced the same
      hypotensive effect as it did in pretreated conditions, although the hypotensive
      effect of monatepil was attenuated by 20-35% as compared with pretreated
      conditions. These results suggest that monatepil exerts alpha 1-adrenoceptor
      blocking action in vivo and 20-35% of the hypotensive effect of monatepil is
      attributed to its alpha 1-adrenoceptor blocking activity.

PMID- 7564366
TI  - Effects of chronic nifedipine treatment on streptozotocin-induced diabetic rats.
AB  - We studied the effects of 6-week treatment with nifedipine (35 mg/kg/day orally,
      p.o.) on streptozotocin (STZ)-induced diabetic rats. Injection of STZ [45 mg/kg
      intravenously, (i.v.) single dose] produced a significant increase in blood
      pressure (BP), bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia,
      hypothyroidism, depression in left ventricular developed pressure (LVDP),
      cardiomyopathy, and nephropathy. Treatment of diabetic rats with nifedipine
      normalized the BP and prevented bradycardia. Insulin levels were decreased after
      nifedipine treatment in diabetic as well as nondiabetic rats. However, serum
      glucose levels were also partially decreased in diabetic animals by nifedipine
      treatment. In control animals as well, glucose levels were in the normal range
      despite lower insulin levels observed after nifedipine treatment. Nifedipine
      treatment significantly prevented STZ-induced increase in cholesterol and
      triglyceride levels. Nifedipine treatment significantly prevented STZ-induced
      hypothyroidism and also prevented STZ-induced cardiac depression and
      cardiomyopathy. Our data indicate that nifedipine increases insulin sensitivity
      and has some beneficial effects on cardiovascular parameters. It may therefore be
      considered a preferred drug in the treatment of hypertension associated with
      diabetes mellitus.

PMID- 7564367
TI  - Comparative effects of losartan, captopril, and enalapril on murine acute
      myocarditis due to encephalomyocarditis virus.
AB  - Losartan, a recently developed nonpeptide angiotensin II (AII) receptor
      antagonist, was orally administered for 14 days to mice with viral myocarditis,
      beginning 7 days after encephalomyocarditis virus inoculation. The angiotensin
      converting enzyme inhibitors (ACEI) captopril and enalapril were also
      administered in the same manner to compare the therapeutic effects of these three
      drugs on the degree of myocarditis, acute heart failure, and left ventricular
      (LV) hypertrophy. Heart weight and the heart weight/body weight ratio were
      reduced by losartan (60 mg/kg/day) and captopril (7.5 mg/kg/day), but not by
      enalapril (1 mg/kg/day). LV wall thickness and cavity dimension were decreased in
      the losartan and captopril groups. Captopril reduced both myocardial necrosis and
      inflammation, whereas enalapril reduced myocardial necrosis but not inflammation.
      However, none of the studied losartan doses (1.2, 12, 60 mg/kg/day) influenced
      myocardial necrosis and inflammation resulting from viral infection. Thus,
      specific blockade of AII is beneficial in congestive heart failure (CHF) and LV
      hypertrophy but is not effective in viral-evoked inflammation and injury.

PMID- 7564368
TI  - Tissue- and subtype-specific modulation of angiotensin II receptors by chronic
      treatment with cyclosporin A, angiotensin-converting enzyme inhibitors and AT1
      antagonists.
AB  - We wished to determine whether chronic treatment of rats with cyclosporin A
      (CSA), an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor
      antagonists modulates the angiotensin receptor density. In rats treated
      chronically with CSA, the vasoconstrictor response to angiotensin II (AII) is
      increased and this increase is modulated by ACEI and angiotensin receptor
      antagonists. Rats were treated for 6 weeks orally with CSA (15 mg/kg/day), the
      ACE inhibitor lisinopril (10 mg/kg/day), the angiotensin receptor antagonists DUP
      753 (10 mg/kg/day), and D 8731 (10 mg/kg/day) and the combinations CSA +
      lisinopril, CSA + DUP 753, and CSA + D 8731. Olive oil was used as a control. The
      number of total AII receptors (Bmax) was determined by Scatchard analysis of
      [125I]Sar1 Ile8 AII binding in kidney, liver, adrenal cortex, and adrenal
      medulla. The receptor subtypes were analyzed with the specific antagonists DUP
      753 (subtype 1) and PD 123319 (subtype 2). CSA upregulated angiotensin receptors
      in all organs studied. Lisinopril alone downregulated angiotensin receptors and
      abolished the effect of CSA in liver and adrenal cortex and medulla, but not in
      the kidney, where it had no effect. DUP 753 alone downregulated the angiotensin
      receptor subtype 1 in kidney, liver and adrenal cortex; its effect on the adrenal
      medulla in which 89% of angiotensin receptors are subtype 2, did not quite reach
      significance. The combination of DUP 753 and cyclosporin CSA abolished the CSA
      induced increase in angiotensin receptor density in all four organs. The
      angiotensin receptor antagonists D 8731 downregulated the angiotensin receptors
      (subtype 1) in liver and kidney and upregulated angiotensin receptors (subtype 2)
      in the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564369
TI  - Antihypertensive effects of moexipril, a new ACE inhibitor, as add-on therapy to
      nifedipine in patients with essential hypertension.
AB  - Moexipril is a new nonpeptide angiotensin-converting enzyme (ACE) inhibitor with
      an intermediate duration of action. The antihypertensive efficacy and safety of
      moexipril as add-on therapy to nifedipine retard (20 mg b.i.d) was compared to
      placebo during 8 weeks in a double-blind trial with a parallel group design. A
      total of 203 patients with essential hypertension and a sitting diastolic blood
      pressure (DBP) > or = 95 mm Hg on nifedipine alone were randomly assigned to
      placebo or moexipril 3.75 mg o.d., 7.5 mg o.d., or 15 mg o.d.. At endpoint, the
      adjusted mean reductions in DBP from baseline were 6 mm Hg, 9 mm Hg (p < 0.01),
      and 9 mm Hg (p < 0.05) in the moexipril 3.75 mg, 7.5 mg, and 15 mg groups,
      respectively, compared to 5 mm Hg in the placebo group. All dosages of moexipril
      were well tolerated, and the overall percentages of patients who reported adverse
      experiences were smaller than in the placebo group. We concluded that moexipril
      as add-on therapy to nifedipine is well tolerated and gives additional
      antihypertensive effects.

PMID- 7564370
TI  - Increased sensitivity to inhibition by nifedipine of responses of the mesenteric
      artery bed of the SHRSP to noradrenaline is not dependent on alpha 1-adrenoceptor
      subtypes.
AB  - The effects of noradrenaline (NA) on the perfusion pressure of mesenteric
      vascular bed preparations from stroke-prone spontaneously hypertensive rats
      (SHRSP) or weight-matched normotensive Wistar-Kyoto (WKY) rats in the presence of
      chloroethylclonidine (CEC, alpha 1B-adrenoceptor antagonist) or WB4101 (WB, alpha
      1A-adrenoceptor antagonist), with or without the addition of nifedipine, were
      studied. NA caused a greater maximum increase in the perfusion pressure of the
      SHRSP mesenteric bed than that of the WKY, and the EC50 for NA was lower in the
      SHRSP. There was no difference between the normotensive or hypertensive beds in
      the reduction of responses to NA produced by WB or CEC. Nifedipine, in the
      presence of either CEC or WB, further reduced responses to NA, but to a
      significantly greater extent in the SHRSP than in the WKY. There was no
      difference within either group between the additional inhibitory effect of
      nifedipine in combination with CEC or WB. These results confirm that following
      alpha 1-adrenoceptor subtype blockade, the response to NA by the mesenteric bed
      of the SHRSP is more sensitive to inhibition by nifedipine than its WKY
      counterpart. However, the increased sensitivity to the inhibitory effects of
      nifedipine on responses to NA is not a result of preferential linkage of Ca2+
      entry mechanisms to one or other of the alpha 1-adrenoceptor subtypes.

PMID- 7564372
TI  - Endothelium-dependent vasorelaxation caused by various plant extracts.
AB  - In a previous study (Am J Physiol 1993;265: H774-8), we found that certain red
      wines and other grape products caused endothelium-dependent vasorelaxation. In
      the present study, aqueous extracts of a variety of vegetables, fruits, teas,
      nuts, herbs, and spices were tested for their endothelium-dependent relaxing
      ability in vitro. Rings of rat aorta, with or without an intact endothelium, were
      mounted in tissue baths, contracted with phenylephrine, and then exposed to
      diluted plant extracts. Many, but not all, extracts exhibited endothelium
      dependent relaxations that were reversed by NG-monomethyl-L-arginine, a nitric
      oxide synthase inhibitor, which suggested involvement of nitric oxide, the
      endothelium-derived relaxing factor in the response. Furthermore, extracts that
      caused relaxation also increased tissue levels of cyclic GMP, the mediator of
      nitric oxide-induced vascular smooth-muscle relaxation. These results may lend
      further support to mounting evidence that plant foods contain compounds that, if
      absorbed intact and in sufficient quantities, could conceivably be beneficial in
      prevention of cardiovascular disease.

PMID- 7564371
TI  - Clinical efficacy and safety of once-daily diltiazem in patients with stable
      angina pectoris switched from twice-daily diltiazem.
AB  - The maintenance of angina control was assessed in this multicenter (three sites),
      randomized, double-blind, parallel-group study. Patients with stable angina
      pectoris receiving twice-daily sustained-release (SR) diltiazem were switched to
      equivalent doses of once-daily controlled-delivery (CD) diltiazem or to diltiazem
      SR. Patients who were switched from diltiazem SR to diltiazem CD (n = 28)
      experienced a 5% increase in time to termination (p = 0.0004) on the exercise
      tolerance test (ETT), as well as an 8% improvement in time to onset of angina (p
      < 0.0001) on the ETT. A similar trend was observed in patients randomized to
      diltiazem SR (n = 7), which suggested a training effect, and, therefore, equal
      efficacy between diltiazem SR and diltiazem CD. During exercise testing in the
      diltiazem SR baseline phase, 77% of the patients did not experience angina,
      whereas 60% of the patients did not experience ST-segment depression. Following
      transfer to diltiazem CD, 79 and 61% of patients, respectively, remained angina-
      and ST-segment depression free. No significant changes in the number of angina
      attacks, nitroglycerin use, or any hemodynamic-related parameters were observed
      following transfer to diltiazem CD. Eleven percent of the patients receiving
      diltiazem CD experienced treatment-related adverse events, which were limited to
      headache and abdominal pain; these adverse events did not lead to discontinuation
      of treatment. These findings suggest that patients whose angina is controlled
      with twice-daily diltiazem SR can be safely and effectively switched to an
      equivalent daily dose of the once-daily diltiazem CD.

PMID- 7564373
TI  - Collateral development and angiogenesis after major artery ligation does not
      alter hindquarter vascular reactivity in conscious rabbits.
AB  - We tested whether vasodilator and vasoconstrictor responses of the hindquarter
      vasculature in conscious rabbits were altered 1 day, 2 weeks, and 6 months after
      bilateral superficial femoral artery ligation (SFAL). With pharmacological
      autonomic blockade, hindquarter flow (Doppler flowmeter) was restored to 84% of
      control values 1 day postligation (n = 5). Responses to aortic balloon inflation
      (5-80 s), and intraaortic infusion of norepinephrine, angiotensin II, serotonin,
      acetylcholine, sodium nitroprusside, and adenosine were similar to pre-SFAL
      responses. Two weeks post-SFAL, acrylic casts showed an extensive collateral
      network originating from branches of internal iliac and deep femoral arteries.
      Acetylcholine-induced dilatation was attenuated postligation (n = 7) relative to
      controls (n = 13). Serotonin caused constriction in two rabbits postligation but
      dilatation in all others; however responses to all other agents tested were
      similar to controls. Reactive hyperemia and vascular reactivity were similar in
      rabbits 6 months post-SFAL (n = 5) and controls (n = 5). Thus, despite extensive
      vascular remodeling after SFAL, global hyperemic flow responses of the rabbit
      hindquarter vasculature appeared normal. We found only minimal changes in
      vascular reactivity to constrictor and dilator stimuli. This model of peripheral
      vascular disease does not reflect the clinical syndrome.

PMID- 7564374
TI  - Optimal management of malignant mesothelioma after subtotal pleurectomy:
      revisiting the role of intrapleural chemotherapy and postoperative radiation.
AB  - Malignant pleural mesothelioma (MPM) is a generally fatal disease with no
      standard treatment. There are encouraging reports using intraperitoneal
      chemotherapy to treat peritoneal mesotheliomas and intrapleural chemotherapy
      (IPC) to treat malignant pleural effusions. Our objective was to evaluate the
      efficacy of IPC after subtotal pleurectomy. Between 1988 and 1992, 20 consecutive
      patients with diffuse MPM limited to one hemithorax underwent subtotal
      pleurectomy. Thirteen patients with biopsy-proven MPM known prior to thoracotomy
      were enrolled in a phase II combined modality protocol consisting of
      perioperative intrapleural cisplatin (100 mg/m2) and ara-C (1,200 mg) after
      subtotal pleurectomy, followed by systemic cisplatin (50 mg/m2/week x 8) and
      mitomycin-C (8 mg/m2, days 1 and 36). Seven patients with MPM could not be
      enrolled because their diagnosis was made post-thoracotomy. These patients
      underwent subtotal pleurectomy with (n = 4) or without (n = 3) adjuvant radiation
      (4,500-5,000 cGy in 3 patients, 2,100 cGy in 1 patient). One of three patients
      who developed chemotherapy-related nephrotoxicity died, the only treatment
      related mortality. All 3 patients requiring postoperative readmission received
      IPC. Significant morbidity did not occur in patients not receiving chemotherapy.
      Median survival and time to progression were significantly longer in patients not
      receiving IPC (21 vs. 9 months, P = 0.04; 12 vs. 6 months, P = 0.01). In
      conclusion, intrapleural and postoperative systemic chemotherapy resulted in
      significant toxicity and did not improve survival in our patients who underwent
      subtotal pleurectomy for MPM.

PMID- 7564375
TI  - Prognosis of breast cancer: evidence for interaction between c-erbB-2
      overexpression and number of involved axillary lymph nodes.
AB  - The prognostic significance of c-erbB-2 oncogene amplification or overexpression
      in relation to axillary lymph node metastasis is controversial. We investigated
      this question in 159 cases of operable breast cancer: 56 patients with node
      negative disease and 103 patients with pathological involvement of axillary lymph
      nodes. c-erbB-2 overexpression was assessed by immunohistochemistry using a
      polyclonal antibody raised against a synthetic peptide fragment of the
      oncoprotein. The overall incidence of c-erbB-2 overexpression was 35%. c-erbB-2
      overexpression was significantly related to survival when all patients were
      considered (P = 0.0124), and also for patients with positive axillary lymph nodes
      (P = 0.0026). c-erbB-2 overexpression had no influence on survival of node
      negative patients (P = 0.7972). A multivariate survival analysis using the Cox
      proportional hazard model revealed that number of involved lymph nodes, c-erbB-2
      overexpression, ER status, and tumour size were independently related to
      prognosis (P = 0.0000, 0.0012, 0.0112, and 0.0204, respectively). When an
      interaction term was introduced in the Cox model between c-erbB-2 overexpression
      and number of involved axillary lymph nodes, a statistically highly significant
      interaction between these two factors was observed (P = 0.0002), suggesting that
      the expression of prognostic power of c-erbB-2 overactivity is related to the
      number of involved axillary lymph nodes. The 159 patients were then subdivided
      into three groups: node negative (-ve) (56); 1-6 node positive (+ve) (55); and >
      or = 7 node +ve (48). This cutoff criterion gave the most numerically equitable
      distribution of the 159 patients into three groups. The relative risk of death
      increased stepwise from 0.86 (95% CI 0.26-2.78) for node negative patients, to
      1.95 (95% CI 0.82-4.63) for 1-6 node positive patients, to 2.23 (95% CI 1.15
      4.35) for > 7 node positive patients. Our results suggest that the prognostic
      influence of c-erbB-2 overexpression increases arithmatically with increasing
      number of involved axillary lymph nodes.

PMID- 7564378
TI  - Intraoperative radiation therapy for locally advanced recurrent rectal or
      rectosigmoid cancer.
AB  - Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A
      treatment program of external beam irradiation, surgery, and intraoperative
      irradiation has been used for 41 patients. The 5-year actuarial local control and
      disease-free survival of all 41 patients was 30% and 16%, respectively. Subset
      analysis demonstrated differences in outcome by extent of surgical resection. The
      5-year actuarial local control and disease-free survival of 27 patients
      undergoing complete resection was 47% and 21%, respectively. By contrast, the
      outcome of 14 patients undergoing partial resection was poor, with a 5-year
      actuarial local control and survival of 21% and 7%, respectively. Late
      complications included soft tissue or peripheral nerve injury, with many of these
      resolving within 4-18 months. Local control and disease-free survival rates are
      favorable in comparison with the results achieved by aggressive surgery. Patients
      who achieve a gross total resection at intraoperative irradiation have a markedly
      better prognosis than that of patients with residual gross disease.

PMID- 7564377
TI  - Hepatic artery chemoembolization or embolization for primary and metastatic liver
      tumors: post-treatment management and complications.
AB  - This paper describes complications and patient management issues associated with
      hepatic arterial chemoembolization (HACE) and embolization (HAE) used to treat
      liver malignancies and characterizes patient survival based on histologic tumor
      type. We performed a retrospective review of all patients treated with HACE or
      HAE between January 1, 1988 and December 31, 1990. During the study period, 314
      HACEs and HAEs were performed in 121 patients. Ninety-six of the patients (79%)
      were treated for neoplasms metastatic to the liver. The morbidity rate following
      HACE and HAE in this study was 5.1%. The major complications included portal vein
      thrombosis, hepatic abscess, and liver failure. The treatment-related mortality
      rate was 4.1%. Fever and ileus were the most common management problems following
      HACE or HAE. Median survival for patients with liver metastases varied according
      to histologic type, and median survival for patients with hepatocellular cancer
      was 306 days. Morbidity and mortality from HACE and HAE to treat liver tumors can
      be minimized by proper selection and careful management of patients. HACE or HAE
      alone was not curative in any of these 121 patients. An understanding of
      treatment-related side effects is necessary to aid in the management of patients
      following HACE or HAE.

PMID- 7564376
TI  - Collagen promotes perianastomotic tumour growth in an experimental animal model.
AB  - Local application of growth factors promote wound healing and may find clinical
      application for use in high-risk intestinal anastomoses such as that following
      anterior resection. Since viable tumour cells are present in the bowel lumen and
      circulation after curative colorectal cancer surgery, it is unclear what effect
      such factors may have on tumour recurrence. The aim of this study was to examine
      the effect of epidermal growth factor (EGF) and basic fibroblast growth factor
      (bFGF) in a collagen suspension on perianastomotic tumour growth in an animal
      model. Significantly (P < 0.05) more animals in the collagen treated groups
      developed anastomotic tumours. The area of tumour growth at the anastomosis was
      also significantly greater for the collagen (median 14.7 mm2) and collagen + EGF
      (median 10.8 mm2) groups compared with controls (median 0.78 mm2). We were unable
      to demonstrate any promotion of tumour by growth factors alone. Collagen promotes
      perianastomotic tumour growth in this model and is not a suitable vehicle for
      growth factor application in colorectal cancer surgery.

PMID- 7564379
TI  - Sinus histiocytosis mimicking metastatic melanoma in lymph nodes of a patient
      with a large joint prosthesis: case report and review of the literature.
AB  - Malignant melanoma metastases to regional lymph nodes may be mimicked by several
      non-neoplastic processes, including sinus histiocytosis induced by fragments shed
      from joint prostheses. A patient who had an elective lymph node dissection for
      malignant melanoma and was found to have "post-prosthesis lymph node
      histiocytosis" resembling metastatic disease is described. Knowledge of the
      patient's past history of a total shoulder joint replacement along with the use
      of polarized light microscopy to identify birefringent particles of prosthetic
      debris allows for an accurate histologic diagnosis.

PMID- 7564380
TI  - Acute appendicitis secondary to metastatic nasopharyngeal carcinoma.
AB  - This is a review of a rare case of acute appendicitis secondary to metastatic
      nasopharyngeal carcinoma (NPC) that had never before been reported in the
      literature. The clinical presentation did not differ from usual cases of acute
      appendicitis, but the pathology caused us to re-evaluate the NPC stage of the
      patient.

PMID- 7564381
TI  - Preoperative embolization of osseous metastases from hypervascular cancers.

PMID- 7564382
TI  - The need to recognize germ cell tumor in metastatic poorly differentiated
      carcinoma with unknown primary site.

PMID- 7564383
TI  - Rates of growth of human solid neoplasms: Part I.
AB  - The purpose of this article is to consolidate data collected from a variety of
      sources that have permitted calculations of the rates of growth of human
      neoplasms. These sources include Fischel State Cancer Hospital (Columbia, MO);
      Mallinckrodt Institute of Radiology, (St. Louis, MO); Roentgen Diagnostic
      Institute, Allmanna Sjukhuset (Malmo, Sweden); University of Louisville
      (Louisville, Kentucky); University of Heidelberg (Heidelberg, Germany); and St.
      Luke's Hospital (St. Louis, MO). Included in the data are laboratory measurements
      of cell replication rates. All gross measurements were made either on imaging
      studies or with a centimeter scale for surface or palpable neoplasms. Data have
      been reported for breast and pulmonary cancers and metastases of many types,
      melanomas, skeletal sarcomas, benign and malignant colonic neoplasms, and
      isolated cases of less frequent neoplasms. Related cytokinetic measurements by
      tritriated thymidine labelling, bromodeoxyuridine labelling, S-phase fraction
      from DNA flow cytometric analysis, and mitotic indices are discussed. The various
      mathematical formulae applicable to the analysis of the collected data and the
      determination of rates and patterns of growth are included. Also considered are
      the clinical implications of these data and the importance of ever better
      knowledge on the cytokinetics of human cancer. Prior studies on the evolution of
      insight into this field are cited and discussed. The authors conclude that a more
      accurate quantification of the growth rates of human cancer is essential for
      understanding the biological variance of human cancers seen clinically.

PMID- 7564385
TI  - Treatment of breast cancer in elderly patients.
AB  - The objective of this study was to analyze the treatment and its results in
      breast cancer of the elderly. Special attention was given to the primary
      treatment with tamoxifen alone. We reviewed 210 patients over 70 years old with
      breast cancer treated between 1980 and 1992. Mean follow-up time was 41 months.
      Tamoxifen was given as primary treatment in 34 patients without distant
      metastases; 147 patients without distant metastases underwent surgery. Local or
      regional recurrence occurred in 6% of the patients who had surgery. Local
      progressive disease was reported in 27% of those treated with tamoxifen (P <
      0.005). These patients had further surgery. There was no difference between the
      two groups in overall survival of patients and occurrence of metastases. We
      concluded that optimal treatment of breast cancer in the elderly should include
      surgery. Only patients with very limited life expectancy should receive tamoxifen
      alone.

PMID- 7564384
TI  - Small hepatocellular carcinoma of single nodular type: a specific reference to
      its surrounding cancerous area undetected radiologically and macroscopically.
AB  - A total of 128 surgically resected small hepatocellular carcinomas, measuring
      less than or equal to 3 cm in diameter, were studied by both macroscopic and
      histologic examinations. In 95 single nodular-type tumors of the 128 lesions,
      eight tumors were associated with the cancerous areas of well differentiated
      hepatocellular carcinoma around the nodule. These surrounding cancerous areas
      went undetected by both the preoperative radiological examinations and the gross
      findings of resected specimens. Based on the immunohistochemical findings, the
      labeling index, both of the proliferating cell nuclear antigen (PCNA) and of the
      Ki-67 in the surrounding cancerous areas, were lower than that of the main
      nodules but higher than in the nontumorous liver parenchyma in seven of eight
      cases. These results suggest that the main nodule was generated from the
      surrounding cancerous area, supporting the hypothesis of a stepwise progression
      of HCC. Even if the tumor seems to be a small and single nodular type, it is
      recommended that its surrounding areas should be closely examined and the
      surgical cutting margin should be made more than 1.0 cm away from the main nodule
      at hepatic resection.

PMID- 7564386
TI  - Total gastrectomy for early gastric cancer.
AB  - A total gastrectomy was performed in 49 patients with early gastric cancer, and
      the effectiveness of this procedure was evaluated by reviewing the hospital files
      of the patients. The reasons for this total gastrectomy were as follows: (1)
      lymph node dissection for 22 patients, (2) surgeon's choice in reconstruction for
      10 patients, (3) modification of the surgery from subtotal to total gastrectomy
      for seven patients, (4) synchronous multiple cancers for seven patients, and (5)
      cancer in a stomach remnant for three patients. Of 49 patients, 42 had the
      cancerous lesions in the upper portion of their stomachs. Lymph node involvement
      occurred in 5 patients, but not in the supra- or infrapyloric lymph nodes.
      Postoperative complications such as anastomotic leakage, reflux esophagitis and
      pancreatic fistula occurred in five, four, and two patients, respectively.
      Postoperative death, including two patients who died within 30 days after the
      surgery, occurred in 5 patients. Our study showed that total gastrectomy resulted
      in excessive unnecessary surgery in 39 out of 49 patients (79.6%). We conclude
      that a total gastrectomy should not be performed on patients with early gastric
      cancer except for synchronous multiple cancers and for cancers in a stomach
      remnant.

PMID- 7564387
TI  - Typical medullary carcinoma of the breast: a clinical and pathological analysis
      of 52 cases.
AB  - Fifty-two women with typical medullary breast carcinoma, diagnosed according to
      criteria of Ridolfi et al. [Cancer 40:1365-1385, 1977] are described. At the time
      of diagnosis, 90% of the patients were stages I and II. The primary tumor size
      was < or = to 4 cm in 46 (88.5%) and > 4 cm in 6 (11.5%) patients. Axillary lymph
      nodes were microscopically negative in 35 (67.3%) and positive in 17 (32.7%)
      patients. All 52 women underwent the Patey operation. Seventeen patients with
      microscopically positive axillary lymph nodes received postoperative irradiation.
      Of the 52 treated patients, 44 (84.6%) survived 10 years NED. The only prognostic
      factor was the microscopical axillary lymph nodes status. In the group of pNO
      patients, 97.1% survived 10 years NED, pN+ 58.8% only. The sole causes of
      unsuccessful treatment were distant metastases to lungs, hepar, and bones.
      Typical medullary carcinoma is a favorable histological type of breast carcinoma
      with very good prognosis for pNO patients.

PMID- 7564388
TI  - Expression and loss of heterozygosity of c-met proto-oncogene in primary breast
      cancer.
AB  - The c-met proto-oncogene encodes the receptor to hepatocyte growth factor-scatter
      factor (HGF-SF), a mesenchyme-derived cytokine with cell-dissociating, invasion,
      and angiogenic properties. The expression of c-met in breast cancer is the
      subject of controversy; 111 primary breast cancers were examined for LOH of c-met
      by Southern blot electrophoresis. c-met expression was measured in a further 40
      patients with breast cancer and in 8 patients with benign breast disease by flow
      cytometry. LOH of c-met was detected in only 4% of informative breast cancers.
      Expression of c-met was significantly greater in patients with breast cancer than
      in those with benign breast disease (P < 0.01, Mann-Whitney). There was no
      correlation however between increased c-met expression and clinicopathological
      prognostic variables. These results do not support the role of c-met as a tumour
      suppressor gene in breast cancer but suggest increased receptor expression in
      malignant breast disease. The significance of this increased expression in breast
      cancer is the subject of further investigation.

PMID- 7564389
TI  - Non-Newtonian flow of blood in an arteriosclerotic blood vessel with rigid
      permeable walls.
AB  - The steady, laminar and fully developed flow of blood in an arteriosclerotic
      blood vessel with rigid permeable walls is investigated, taking into account the
      slip condition at the vessel walls. The constitutive equation of blood is
      represented by a Casson fluid model. The model is used to study the influence of
      the yield stress on blood flow through arteriosclerotic arteries. The variation
      of the flow resistance and wall shear stress, with permeability parameter, slip
      parameter and Casson number are obtained for different sizes of growth of the
      arteriosclerotic lesions. Comparison of the results is made with available
      results that consider the impervious wall and those that consider blood as a
      Newtonian fluid. It is found that permeability has a significant effect on the
      values of flow resistance and wall shear stress. Biological implications of the
      present model on different arterial diseases are discussed.

PMID- 7564391
TI  - Fractal dimension of exon and intron sequences.
AB  - In this paper, the concept of fractal is applied to describe the features of
      nucleotide sequences. We introduce the mapping from nucleotide sequences to two
      dimensional metric space. Then we use this mapping to study quantitatively the
      self-similarity of exon and intron sequences in different scales. We find that
      self-similarity exists in the geometrical range and main range of a nucleotide
      sequence and define the fractal dimension in these ranges. The results show that
      the fractal properties of exon sequences are quite different from those of
      introns, reflecting their difference in structure and function. The fractal
      dimension of the geometrical range may be used to predict the exon regions of a
      raw nucleotide sequence.

PMID- 7564390
TI  - Modeling positive and negative selection and differentiation processes in the
      thymus.
AB  - T cells begin their development as precursor cells in the bone marrow. These
      cells migrate to the thymus, where they further divide, differentiate, and mature
      into functional T cells. Most thymocytes (95-99%) die in the course of this
      process, and only relatively few exit the thymus as mature cells. Here we develop
      a differential equation model of cell proliferation, differentiation and death in
      the thymus that can account for both the total number of thymus cells and the
      fractions of various types of immature and mature thymocytes. Our model suggests
      that positive and negative selection may have more complex effects than simply
      deleting some cells and allowing others to survive.

PMID- 7564392
TI  - Restricted intramolecular energy flow in the enzyme-substrate complex.
AB  - The fate of the energy released during the formation of the enzyme-substrate
      complexes is discussed in connection with energetic aspects of the one-substrate
      enzyme-catalysed reaction. Assuming a free and rapid intramolecular energy flow
      in the complex, the high enzyme catalytic activity cannot be explained. It is
      suggested that a metal ion near the active site can serve as a barrier to the
      energy flow from the binding sites of the complex into the enzyme molecule. The
      effective vibrational temperature of the bonded substrate molecule is then higher
      than the temperature of the reaction system.

PMID- 7564393
TI  - Tandem genes and clustered genes.
AB  - Two patterns of gene repetition are described: tandem arraying and clustering.
      Tandemly arrayed genes reside within segments of DNA that are repeated head-to
      tail a number of times. Clustered genes are linked but irregularly spaced, are
      often mutually inverted in an unpredictable pattern and are connected by non
      conserved DNA. Tandem arrays are homogenized by both unequal recombination and
      gene conversion, are necessary for the maintenance of large gene families, can
      expand and contract rapidly in response to changing demand, can keep functionally
      related genes equal in number, and do not engender increased genetic complexity.
      Gene clusters are homogenized by conversion only, seldom if ever contain more
      than 50 members, are stable in number, and often engender increased genetic
      complexity. The interrelationships among these properties are discussed. Tandem
      gene arrays can evolve into gene clusters. It is suggested that this occurs when
      some change in the array inhibits unequal recombination but not gene conversion.
      The most common such change is inversion of part of the tandem array with respect
      to the rest; however, arrays can evolve into clusters without inversion.
      Clustered genes are sometimes re-amplified into new tandem arrays. Clustered
      genes are probably more durable than tandemly arrayed genes during periods of
      relaxed selection, and in the case of fish antifreeze protein genes, seem to
      behave as a genetic memory.

PMID- 7564394
TI  - Learning and evolution: a quantitative genetics approach.
AB  - Recent models of the interactions between learning and evolution show that
      learning increases the rate at which populations find optima in fixed
      environments. However, learning ability is only advantageous in variable
      environments. In this study, quantitative genetics models are used to investigate
      the effects of individual learning on evolution. Two models of populations of
      learning individuals are constructed and analyzed. In the first model, the effect
      of learning is represented as an increase in the variance of selection. Dynamical
      equations and equilibrium conditions are derived for a population of learning
      individuals under fixed and variable environmental selection. In the second
      model, the amount of individual learning effort is regulated by a second gene
      specifying the duration of a critical learning period. The second model includes
      a model of the learning process to determine the individual fitness costs and
      benefits accrued during the learning period. Individuals are then selected for
      the optimal learning investment. The similarities of the results from these two
      models suggest that the net effects of learning on evolution are relatively
      independent of the mechanisms underlying the learning process.

PMID- 7564395
TI  - Theoretical analysis of the regulation of interferon expression during priming
      and blocking.
AB  - Interferon superinduction, in the case of cell pretreatment with low doses of
      interferon (priming), may be explained by activation of 2',5'-oligoadenylate
      synthetase and endonuclease L, since the latter, as expected, leads to a more
      rapid amplification of the standard scheme of interferon induction based on the
      antirepression mechanism. In the given case, endonuclease L will further increase
      the degradation rates for messages, which encode repressor proteins controlling
      interferon gene expression. Under ordinary induction, these messages are
      destroyed only by short-lived nuclease activated by double-stranded RNA. Cell
      pretreatment with high doses of interferon (blocking) considerably increases the
      concentrations of protein kinase and 2',5'-oligoadenylate synthetase in the cell.
      However, it seems that during blocking protein kinase plays the main role in
      inhibition of interferon synthesis, and this leads to almost complete depression
      of translation in the cell. When protein kinase is not sufficiently activated,
      blocking does not occur since treatment of cells with high concentrations of
      interferon does not hinder priming induced by 2',5'-oligoadenylate synthetase and
      endonuclease L. The proposed model is consistent with the findings that both
      interferon-treated primed and blocked cells are able to produce interferon more
      rapidly than normal cells. The analysis, based on a computer simulation model,
      suggests that priming and blocking of interferon may be based on processes
      controlling its induction and antiviral activity.

PMID- 7564396
TI  - Evolution of altruism in optional and compulsory games.
AB  - In "optional" variants of the iterated prisoner's dilemma, players may choose
      whether or not to participate. Members of evolving populations playing optional
      variants of the iterated prisoner's dilemma by following inherited strategies
      tend to cooperate more than do members of populations playing the standard,
      "compulsory" version. This result is due to dynamical properties of the evolving
      systems: the populations playing the compulsory game can become stuck in states
      of low cooperation that last many generations, while the optional games provide
      routes out of such states to states of high cooperation. Computational
      simulations of the evolution of populations playing these games support these
      analytic results and illustrate the interactions between the genetic
      representation of strategies and the composition of populations in which those
      strategies are deployed.

PMID- 7564397
TI  - Cell cycle progression: computer simulation of uncoupled subcycles of DNA
      replication and cell growth.
AB  - A computer simulation is presented for cell proliferation in a structured cell
      cycle model. The simulation takes into account the idea that DNA replication and
      cell growth are two loosely coupled subcycles. The simulation experiments
      performed offer an explanation for the close correlation often found in
      interdivision times of sister cell pairs and demonstrate that the exponential
      slope of the so-called beta-curve is linked to an exponential increase in cell
      mass. However, in synchronization experiments, a linear increase in mean mass of
      a cell population develops over time. A channel is opened for a genetic and
      growth rate influence extending from grandparent to granddaughter. Positive and
      negative time correlations close to zero still occurred for mother-daughter cell
      cycles. The computer program leaves two sites in the cell cycle available for
      gene, molecular and size checkpoints, one in G1 and one in G2. The simulation
      experiments bridge the gap between models considering (i) size control, (ii)
      transition probability, and (iii) inherited properties as interpretations of cell
      cycle progression and are applicable to embryonic cells with the potential to
      differentiate, somatic cells, and to the kinetics of activation of serum-starved
      cells. A G0 state is also defined.

PMID- 7564398
TI  - Relation between adiabatic and pseudoadiabatic compressibility in ultrasonic
      velocimetry.
AB  - A fundamental problem in measurements of the adiabatic compressibility of
      macromolecules in aqueous solution using sound velocity is the unknown heat
      exchange between the interior of the molecule and the bulk solvent. Usually only
      a pseudoadiabatic compressibility is measured, which is between isothermal and
      adiabatic compressibility. The measured compressibility might even be close to
      the isothermal compressibility, depending on the experimental conditions. In this
      paper, a model is proposed that enables the deviation of experimental conditions
      from the requirement of adiabatic measurements to be estimated. This model treats
      the macromolecule as a heat conductive sphere. Analytical solutions for the
      temporal and local heat diffusion are obtained. Proteins less than 100 kDa in
      molecular weight at a sound frequency of less than 10 MHz are found to be
      essentially in thermal equilibrium with the bulk solvent. In this case, for the
      aqueous protein solution at temperatures < or = 25 degrees C and less than 2%
      protein concentration, the theory predicts that the sound velocity measurement of
      the interior of protein is close to isothermal conditions.

PMID- 7564399
TI  - Entropy, irreversibility and evolution.
AB  - The Second Law of Thermodynamics is investigated with respect to its value as an
      indicator of the direction of the evolutionary process. Non-thermodynamic entropy
      concepts and possible errors in the use of thermodynamic entropy are discussed.
      The importance of genuine thermodynamic potentials and their correct application
      for understanding processes is emphasized. There is no direct connection between
      evolutionary events such as speciation and thermodynamic entropy changes; the
      irreversibility of evolution is not a consequence of thermodynamic
      irreversibility.

PMID- 7564400
TI  - A simple model of K+ channel activation in nerve membrane.
AB  - A model is proposed for activation of potassium ion channel current, IK, in squid
      giant axons, which consists of two closed states and one open state. The rate
      parameter in the forward direction between the two closed states depends upon
      previous history. That is, it relaxes exponentially to its steady-state value
      appropriate to the membrane potential of a voltage clamp step rather than change
      instantaneously as in traditional models of channel gating. The model
      successfully describes both the enhancement of the delay in activation of IK with
      relatively negative prepulse potentials, i.e. the Cole-Moore effect, and the time
      dependent rising phase of "on" gating current, which has been reported recently
      for several types of potassium channels.

PMID- 7564401
TI  - The effect of point of expression on ESS sex ratios.
AB  - The sex ratio produced by an individual may be a consequence of relative
      frequencies of genotypes amongst offspring, or may result directly from parental
      (maternal) control. We analyse the evolutionarily stable sex ratio for a
      hypothetical organism in which both forms of sex ratio expression can occur. We
      prove that the point of expression of sex ratio does not affect the
      evolutionarily stable sex ratio for diploid hosts in populations infected with
      cytoplasmically inherited sex ratio distorters.

PMID- 7564402
TI  - What KNA did for me: the story of a St. Anthony nurse.

PMID- 7564403
TI  - Focus on diversity.

PMID- 7564404
TI  - Affordable preventive health screening: mammograms for older African American
      women.

PMID- 7564405
TI  - Use of bicycle helmets.

PMID- 7564406
TI  - Factors associated with non-compliance in follow-up human immunodeficiency virus
      testing among healthcare workers after blood and/or body fluid exposure.

PMID- 7564407
TI  - Nurses rally to raise awareness of issues, inform patients of care.

PMID- 7564408
TI  - What is a certified registered nurse anesthetist?

PMID- 7564409
TI  - Nursing--the centerpiece of health care.

PMID- 7564410
TI  - Nursing practice cabinet poster sessions: getting the word out!

PMID- 7564411
TI  - Focus on diversity.

PMID- 7564412
TI  - Traditional medicine in Turkey. V. Folk medicine in the inner Taurus Mountains.
AB  - Folk medicine in the inner region of the Taurus Mountains in south Anatolia has
      been studied; 256 remedies prepared from 124 plant and 3 animal species are
      listed. Data include vernacular names, the parts used, the methods of preparation
      of the drugs and the medicinal use.

PMID- 7564413
TI  - Screening of selected medicinal plants of Nepal for antimicrobial activities.
AB  - In an ethnopharmacological screening of selected medicinal plants used in Nepal,
      methanol extracts from 21 plant species were assayed for activity against 8
      strains of bacteria and 5 strains of fungi. Duplicate assays were conducted with
      and without exposure to UV-A radiation to test for light-activated or light
      enhanced activity. All 21 of the extracts showed activity against at least 2
      bacterial strains, and 20 showed activity against at least 2 fungi. Six extracts
      were active only when exposed to UV-A light, and the antibiotic or antifungal
      effect of 14 extracts was enhanced upon exposure to light.

PMID- 7564414
TI  - Effects of Dalbergia subcymosa Ducke decoction on rats and their offspring during
      pregnancy.
AB  - In order to evaluate Dalbergia subcymosa Ducke stem bark decoction for possible
      embryo-fetotoxicity effects and disturbance of postnatal development of pups,
      female rats were treated on days 6-15 of pregnancy with either the decoction (40
      mg/rat) or distilled water (0.5 ml/rat), by gastric intubation. Half of the
      animals were killed on day 20 and the other half was allowed to deliver.
      Maternal, fetal and newborn studies suggest absence of embryo-fetotoxicity and no
      disturbance of postnatal development of the pups indicating that the beverage may
      be safe for human use as an anti-inflammatory.

PMID- 7564415
TI  - Anti-ulcer effect of the hot water extract of black tea (Camellia sinensis).
AB  - The effect of the hot water extract of black tea (Camellia sinensis (L.) O.
      Kuntze, Theaceae) on ulceration induced by various ulcerogens and by cold
      restraint stress (CRS) was investigated in albino rats. While prior
      administration of tea extract for 7 days significantly reduced the incidence of
      ulcer, ulcer number and ulcer index produced by aspirin, indomethacin, ethanol,
      reserpine and CRS, it failed to inhibit the ulcers induced by serotonin and
      histamine. Tea extract also favourably altered the changes in acid and peptic
      activity of gastric secretion induced by aspirin, indomethacin, ethanol,
      reserpine and CRS. The observations suggest that the hot water extract of black
      tea possesses anti-ulcer activity, probably mediated through prostaglandins.

PMID- 7564416
TI  - Scavenging effects of Mallotus repandus on active oxygen species.
AB  - The active oxygen species scavenging potencies of Mallotus repandus (Willd.)
      Muell.-Arg. extracts were evaluated by the electron spin resonance (ESR) spin
      trapping technique. Superoxide radical (O2.-) and hydroxyl radical (OH.) were
      supplied enzymatically from hypoxanthine-xanthine oxidase (HPX-XOD) reaction and
      hydrogen peroxide-ferrous sulfate (Fenton reaction), respectively, to the assay
      system. The ethyl acetate fraction of Mallotus repandus (stem) showed the
      greatest superoxide radical scavenger activity and the n-hexane fraction of
      Mallotus repandus (stem as well as root) the greatest hydroxyl radical scavenger
      activity.

PMID- 7564417
TI  - Pharmacology of Casimiroa edulis; III. Relaxant and contractile effects in rat
      aortic rings.
AB  - The relaxant and contractile effects of an aqueous extract of the seeds of the
      hypotensive plant Casimiroa edulis were investigated in rat aortic rings. The
      extract inhibited contractions elicited by noradrenaline, serotonin and
      prostaglandin F2 alpha, but did not affect responses to KCl. Inhibition did not
      require the presence of intact vascular endothelium and was not affected by
      histamine antagonists. In this preparation, the extract also elicited
      concentration-related contractions which were more marked in the absence of
      endothelium, were not blocked by histamine antagonists, and were completely
      suppressed by alpha-adrenergic blockade. It was concluded that the relaxant
      effect of the extract is not exerted through release of an endothelial relaxing
      factor nor through blockade of calcium channels or of specific smooth muscle
      receptors, and does not involve histaminergic mechanisms. The contractile effect
      is modulated by vascular endothelium and is alpha-adrenergic in nature.

PMID- 7564418
TI  - Ethnopharmacology of bear gall bladder: I.
AB  - Both bear and pig bile solutions were shown to have anti-inflammatory,
      anticonvulsion and analgesic effects, and also to prolong the survival time of
      mice in hypoxic conditions. It is possible that pig gall bladders could be
      developed as an alternative to bear gall bladders for uses in certain
      prescriptions of Chinese medicine.

PMID- 7564419
TI  - Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma
      lucidum and Ganoderma neo-japonicum.
AB  - The free radical scavenging and antihepatotoxic activity from Ganoderma lucidum,
      Ganoderma formosanum and Ganoderma neo-japonicum were studied. Treatment with the
      water extract of Ganoderma lucidum, Ganoderma formosanum and Ganoderma neo
      japonicum caused a marked decrease in the CCl4-induced toxicity in rat liver,
      made evident by their effect on the levels of glutamic oxaloacetic transaminase
      (GOT) and lactic dehydrogenase (LDH) in the serum. The scavenging potency of the
      water extracts of the crude drugs was evaluated in terms of their ability to
      reduce the peaks of spin adducts using electron spin resonance (ESR) spin
      trapping techniques. The results indicated that Ganoderma formosanum showed the
      greatest antihepatotoxic activity and the greatest free radical scavenging
      activity.

PMID- 7564420
TI  - Evaluation of the protective potential of Artemisia maritima extract on
      acetaminophen- and CCl4-induced liver damage.
AB  - The hepatoprotective activity of the aqueous-methanolic extract of Artemisia
      maritima was investigated against acetaminophen (paracetamol, 4-hydroxy
      acetanilide)- and carbon tetrachloride (CCl4)-induced hepatic damage.
      Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice, while
      pretreatment of animals with the plant extract (500 mg/kg) reduced the death rate
      to 20%. Acetaminophen at the dose of 640 mg/kg produced liver damage in rats as
      manifested by the significant (P < 0.001) rise in serum levels of glutamate
      oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 1529
      +/- 172 I.U./l and 904 +/- 116 I.U./l (n = 10), respectively, compared to
      respective control values of 87 +/- 12 I.U./l and 31 +/- 5 I.U./l. Pretreatment
      of rats with the plant extract (500 mg/kg) lowered significantly (P < 0.001) the
      respective serum GOT and GPT levels to 112 +/- 10 I.U./l and 47 +/- 11 I.U./l.
      Similarly, a hepatotoxic dose of CCl4 (1.5 ml/kg, orally) raised significantly (P
      < 0.01) the serum GOT and GPT levels to 463 +/- 122 I.U./l and 366 +/- 58 I.U./l
      (n = 10), respectively, compared to respective control values of 92 +/- 18 I.U./l
      and 35 +/- 9 I.U./l. The same dose of plant extract (500 mg/kg) was able to
      prevent significantly (P < 0.01) the CCl4-induced rise in serum transaminases and
      the estimated values of GOT and GPT were 105 +/- 29 I.U./l and 53 +/- 17 I.U./l,
      respectively. Moreover, it prevented CCl4-induced prolongation in pentobarbital
      sleeping time confirming hepatoprotectivity and validates the traditional use of
      this plant against liver damage.

PMID- 7564421
TI  - The plant molluscicide Millettia thonningii (Leguminosae) as a topical
      antischistosomal agent.
AB  - The West African legume Millettia thonningii is used in Ghana as an anthelmintic
      and as a purgative agent. A chloroform extract of the seeds of Millettia
      thonningii which is known to be molluscicidal and cercaricidal was topically
      applied to mouse skin 2 and 24 h prior to exposure to Schistosoma mansoni
      cercariae. The presence of Millettia thonningii extract components on the surface
      of the skin appeared to be effective in preventing subsequent establishment of
      infection. The compound responsible for the activity is thought to be the
      isoflavonoid alpinumisoflavone.

PMID- 7564422
TI  - Antiulcer activity of Pteleopsis suberosa.
AB  - The bark Pteleopsis suberosa is commonly used in Mali for the treatment of
      gastric ulcers. The present study evaluated the antiulcerogenic property of
      chloroform, ethanol and aqueous extracts and of decoction of P. suberosa bark
      against ulcer lesions induced by ethanol and indomethacin in rats. The results
      tend to confirm the popular use of the plant.

PMID- 7564423
TI  - Plant-derived triterpenoid sweetness inhibitors.
AB  - Considerable recent attention has been focused on naturally occurring compounds
      with taste-modifying activity, which are of potential use in both dietary
      sweetness management and in gaining a better understanding of the sweet taste
      sensation. This review summarizes information on the phytochemistry and
      biological activity of more than 40 triterpenoid sweetness inhibitors that have
      been isolated from the leaves of three medicinal plants, namely, Gymnema
      sylvestre R.Br. (Asclepiadaceae), Ziziphus jujuba P. Miller (Rhamnaceae), and
      Hovenia dulcis Thunb. (Rhamnaceae).

PMID- 7564424
TI  - In acute lung injury, inhaled nitric oxide improves ventilation-perfusion
      matching, pulmonary vascular mechanics, and transpulmonary vascular efficiency.
AB  - Acute respiratory distress syndrome continues to be associated with significant
      morbidity and mortality related to ventilation-perfusion mismatch, pulmonary
      hypertension, and right ventricular failure. It has been suggested that inhaled
      nitric oxide, which is a selective pulmonary vasodilator, may be effective in the
      treatment of acute respiratory distress syndrome; however, the effects of nitric
      oxide on cardiopulmonary interactions are poorly understood. We therefore
      developed a model of acute lung injury that mimics the clinical syndrome of acute
      respiratory distress syndrome. In our model, inhaled nitric oxide significantly
      reduced pulmonary artery pressure, pulmonary vascular resistance, and pulmonary
      vascular impedance. In addition, inhaled nitric oxide improved transpulmonary
      vascular efficiency and ventilation-perfusion matching, which resulted in
      increased arterial oxygen tension. Although arterial oxygen tension increased,
      oxygen delivery did not improve significantly. These data suggest that by
      improving ventilation-perfusion matching and arterial oxygen tension while
      lowering pulmonary vascular resistance and impedance, nitric oxide may be
      beneficial in patients with acute respiratory distress syndrome. However,
      additional measures to enhance cardiac performance may be required.

PMID- 7564425
TI  - Prognostic factors obtained by a pathologic examination in completely resected
      non-small-cell lung cancer. An analysis in each pathologic stage.
AB  - We attempted to clarify what factors predominantly influence the survival of
      patients with non-small-cell lung cancer in each pathologic stage on the basis of
      information generally obtained by a pathologic examination of completely resected
      non-small-cell lung cancer. The subjects included 243 patients with stage I, 63
      with stage II, and 108 with stage IIIA disease. Pathologic features used in the
      analysis were as follows: the greatest tumor size (< or = 3.0 cm versus > 3.0
      cm), the histologic cell type (squamous versus nonsquamous cell carcinoma), the
      grade of differentiation, and tumor invasion of pleura and vessels. In stage
      IIIA, the extent of the metastasis to the lymph nodes was also included in the
      analysis. The significant prognostic factors (p < 0.05) in stage I demonstrated
      by a univariate analysis of the survival curves included the tumor size, the
      grade of differentiation (well differentiated versus moderately and poorly
      differentiated tumor), pleural involvement, and invasion of the artery and vein.
      In addition, the histologic cell type and the pleural involvement in stage II and
      invasion of the vein and the extent of metastasis to the lymph nodes (N0 and N1
      versus N2) in stage IIIA were also found to be significant prognostic factors. A
      multivariate prognostic factor analysis showed that the grade of differentiation,
      pleural involvement, and venous invasion in stage I; the histologic cell type and
      pleural involvement in stage II; and venous invasion and mediastinal lymph node
      metastasis in stage IIIA were all predominant prognostic factors. These
      observations therefore suggest that a pathologic examination can identify the
      patients with a poor prognosis, which is different among the stages.

PMID- 7564426
TI  - Preoperative and intraoperative ultrasonographic examination as an aid in lung
      cancer operations.
AB  - To assess the extent of tumor invasion in lung cancer, my colleagues and I
      routinely use preoperative transesophageal ultrasonic endoscopy and
      intraoperative ultrasonography in addition to preoperative roentgenography,
      computed tomographic scanning, and other standard procedures. Both
      transesophageal ultrasonic endoscopy and intraoperative ultrasonography allow for
      a real-time assessment of the extent to which the lung cancer has invaded
      adjacent organs and are useful in determining the operability and safety margin
      of the involved organ or organs. We found intraoperative ultrasonography to be
      more accurate than transesophageal ultrasonic endoscopy, because intraoperative
      ultrasonography can be done at any time during the operation, as needed, and the
      probe can be directly applied to the desired location from a variety of angles.
      In contrast, when transesophageal ultrasonic endoscopy is used, the presence of
      air in the lung tissue can interfere with an accurate evaluation of some aspects
      of the tumor. Our results indicate that the sensitivity of transesophageal
      ultrasonic endoscopy and intraoperative ultrasonography is 68.4% and 100%,
      respectively, and the specificity is 81.3% for transesophageal ultrasonic
      endoscopy and 95.5% for intraoperative ultrasonography.

PMID- 7564427
TI  - Transposition of the great arteries [S,D,L]. Pathologic anatomy, diagnosis, and
      surgical management of a newly recognized complex.
AB  - The transposition of the great arteries [S,D,L] complex is delineated for the
      first time from the anatomic, diagnostic, and surgical standpoints in this study
      of 26 cases: 16 surgical and 10 postmortem. Transposition of the great arteries
      with situs solitus of the viscera and atria (S), D-loop ventricles (D), and L
      transposition (L) was characterized by six additional interrelated anomalies that
      largely determined surgical management: (1) ventricular septal defect, usually
      conoventricular, in 96%; (2) malalignment of the conal septum, typically leftward
      and posteriorly, in 80%; (3) right ventricular hypoplasia in 50%; (4) pulmonary
      outflow tract stenosis in 27%; (5) ventricular malposition, such as
      superoinferior ventricles, in 23%; and (6) absent left coronary ostium resulting
      in "single" right coronary artery in 23%. Complete surgical repair was done in
      81% of the surgical patients with a 12.5% hospital mortality rate and no late
      deaths. When there was no pulmonary outflow tract stenosis and intracardiac
      anatomy was uncomplicated, we undertook anatomic repair before 1 month of age.
      However, when pulmonary outflow tract stenosis coexisted, complete repair was
      deferred until after age 1 year, our currently preferred operation being the REV
      procedure (reparation a l'etage ventriculaire). When complex intracardiac anatomy
      precluded biventricular repair, a palliative procedure was performed in 19%
      without mortality. Hence, this experience indicates that surgical management of
      patients with the transposition of the great arteries [S,D,L] complex is
      feasible.

PMID- 7564428
TI  - Total cavopulmonary connection without the use of prosthetic material: technical
      considerations and hemodynamic consequences.
AB  - Total cavopulmonary connection with use of an autogenous intraatrial tunnel to
      create a straight tube between the inferior vena cava and the pulmonary artery
      was attempted in several types of cardiac anomaly in eight consecutive candidates
      for the Fontan operation. A small right atrium with an extraordinary location of
      the inferior vena cava and a short superior vena cava prevented the use of this
      procedure in two cases. By preserving the crista terminalis and the sinus node
      and its arteries we prevented the development of postoperative atrial arrhythmias
      in the short follow-up period, and the P trigger-signal averaged P waves were not
      different from those of other cardiac anomalies. The proximal stump of the
      superior vena cava was not incised in any case to enlarge the anastomosis, even
      when size mismatch between the superior and inferior venae cavae existed, as in a
      case of bilateral superior venae cavae. Stretching the vessels by approximately
      150% was possible and permitted an adequate anastomosis. Cavopulmonary
      connections via the intraatrial tunnel ensured smooth, nonturbulent, somewhat
      pulsatile flow without a pressure gradient. We concluded that the creation of an
      autogenous intraatrial tunnel was possible in many cases without serious
      complications and that this procedure has potential benefit for the pulmonary
      circulation in the aspect of pulsatility.

PMID- 7564429
TI  - Total body water in children with congenital heart disease, before and after
      cardiac surgery.
AB  - The aim of this study was to measure total body water in children with congenital
      heart disease before and after cardiac surgery and to compare the results of
      deuterium and 18oxygen dilution methods. Seventeen children (aged 4 to 33 months)
      were given aliquots of isotopically labeled water 1 week before and 6 hours after
      cardiac surgery. Isotope equilibration and analysis of the declining enrichment
      of daily urine samples allowed calculation of the total body water content.
      Before operation, total body water was significantly elevated (p < 0.001,
      Wilcoxon test); after operation it fell to approximately normal values. This
      finding is in contrast to those of previous reports, but may be explained in that
      the method used for calculation depended on measurements taken over a 7-day
      period rather than on a single measurement of isotope dilution as used elsewhere.
      Nevertheless, these results do suggest that surgery can correct the preoperative
      fluid overload. Comparison of deuterium and 18oxygen dilution methods showed a 2%
      to 2.5% overestimation of the total body water content with deuterium sampling.

PMID- 7564430
TI  - Systemic and pulmonary venous connections in visceral heterotaxy with asplenia.
      Diagnostic and surgical considerations based on seventy-two autopsied cases.
AB  - To facilitate the preoperative diagnosis and surgical management of visceral
      heterotaxy and asplenia, 72 postmortem cases were reviewed with particular
      attention focused on the systemic and pulmonary venous connections. The superior
      vena cava was bilateral in 51 cases (71%), but in 9 cases one of the superior
      venae cavae was partly or totally atretic. Patent bilateral superior venae cavae
      were found in 42 cases (58%) and the superior vena cava was unilateral in 21
      (29%). Although the inferior vena cava was never interrupted, a prominent azygos
      vein was found in 6 cases (8%). Some hepatic veins drained separately from the
      inferior vena cava in 20 cases (28%). An intact coronary sinus was rare (2 cases,
      3%). Anomalous pulmonary venous connection to a systemic vein was total in 42
      (58%) of 72 and partial in 2 (3%) of 72, with obstruction in 24 (55%) of 44.
      Abnormal pulmonary artery branches (severe hypoplasia, localized stenosis, or
      discontinuity) were present in 21 (29%), and these obstructive arterial anomalies
      were associated with a significantly higher prevalence of anomalous pulmonary
      venous connection (p < 0.01) and of pulmonary venous obstruction (p < 0.01).
      Cardiac pulmonary venous connections were found in 28 (39%), with the pulmonary
      veins and the inferior vena cava entering the same atrium in 10 (36%) of 28.

PMID- 7564431
TI  - The Carpentier-Edwards pericardial aortic valve. Ten-year results.
AB  - To evaluate the function of the Carpentier-Edwards pericardial valve in the
      aortic position, we analyzed the results of 310 aortic valve replacements
      performed between 1982 and 1985. Mean age was 64.2 +/- 10.8 years (range 22 to 95
      years); 190 patients (61.3%) were male patients. There were 18 hospital deaths
      (5.8%), and none were valve related. Follow-up of the 292 survivors was 100%
      complete at a mean of 7.8 +/- 2.9 years; 2290 patient-years of follow-up were
      available for analysis. There were 133 late deaths (45.5%). Actuarial survivals
      at 5 and 10 years were 82.5% and 45.9%, respectively. The 10-year actuarial
      freedom from events was 88.7% +/- 2.1% for thromboembolism, 90.9% +/- 1.8% for
      hemorrhage, 94.3% +/- 1.6% for endocarditis, and 91.2% +/- 2.6% for structural
      deterioration. The 153 hospital survivors 65 years of age or older had an
      extremely low incidence of structural valve deterioration, with only four
      explants and 95.5% actuarial freedom from explantation at 10 years, and a
      linearized rate of 0.3 +/- 0.2 per patient-year compared with 88.6% and 0.7 +/-
      0.2 for patients younger than 65 years of age. Twelve valves were explanted for
      structural deterioration. Of these, 11 (93%) had leaflet calcification causing
      stenosis and one had a wear-related leaflet tear. The Carpentier-Edwards
      pericardial valve has a low incidence of valve-related complications. The freedom
      from structural valve deterioration is low at 10 years, particularly in patients
      65 years of age and older.

PMID- 7564432
TI  - Comparative results with the St. Jude Medical and Medtronic Hall mechanical
      valves.
AB  - This study compared the clinical performance of the St. Jude Medical and
      Medtronic Hall mechanical valves in isolated aortic or mitral valve replacement.
      From 1984 to 1993, 349 St. Jude Medical valves (aortic 237, mitral 112) and 465
      Medtronic Hall valves (aortic 272, mitral 193) were implanted in 814 patients at
      the University of Ottawa Heart Institute. The patients had similar preoperative
      characteristics. The hospital mortality rate for aortic valve replacement was
      3.4% with the St. Jude Medical valve and 5.8% with the Medtronic Hall valve (p =
      0.26) and the rate for mitral valve replacement was 8.9% with the St. Jude
      Medical valve and 11.9% with the Medtronic Hall valve (p = 0.54). Actuarial
      estimates of survival and freedom from complications were calculated. At 5 years
      the actuarial probability of survival (including hospital deaths) for aortic
      valve replacement was 86% +/- 3% with the St. Jude Medical valve and 68% +/- 4%
      with the Medtronic Hall valve (p = 0.0001) and for mitral valve replacement was
      75% +/- 7% with the St. Jude Medical valve and 70% +/- 4% with the Medtronic Hall
      valve (p = 0.54). The most common cause of late death was cardiac failure and no
      deaths were caused by structural failure. The 5-year probability of freedom from
      bleeding after aortic valve replacement was 99% +/- 1% with the St. Jude Medical
      valve and 95% +/- 2% with the Medtronic Hall valve (p = 0.06) and after mitral
      valve replacement 99% +/- 1% with the St. Jude Medical valve and 97% +/- 2% with
      the Medtronic Hall valve (p = 0.37). The 5-year probability of freedom from
      thromboembolism after aortic valve replacement was 88% +/- 4% with the St. Jude
      Medical valve and 81% +/- 3% with the Medtronic Hall valve (p = 0.08) and after
      mitral valve replacement was 85% +/- 7% with the St. Jude Medical valve and 77%
      +/- 5% with the Medtronic Hall valve (p = 0.17). Reoperation was uncommon and
      there were no cases of structural valve failure. The 5-year actuarial estimate of
      freedom from reoperation therefore for aortic valve replacement was 99% +/- 1%
      with the St. Jude Medical valve and 96% +/- 2% with the Medtronic Hall valve (p =
      0.09) and for mitral valve replacement was 98% +/- 2% with the St. Jude Medical
      valve and 95% +/- 3% with the Medtronic Hall valve (p = 0.40).(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7564433
TI  - Tricuspid valve replacement: postoperative and long-term results.
AB  - A series of 146 consecutive patients who underwent tricuspid valve replacement at
      the University Brugmann Hospital between 1967 and 1987 was reviewed. Mean age at
      operation was 51.4 years (+/- 12.1 years). Different types of prostheses were
      implanted including porcine and bovine pericardial bioprostheses and older and
      bileaflet mechanical valves. Most patients were severely disabled by their
      cardiac disease before operation, with 30.1% in New York Heart Association
      functional class III and 69.9% in class IV. Operative mortality and hospital
      mortality rates (30 days) were high (16.4%). Incremental risk factors for
      hospital death included icterus (p < 0.005), preoperative hepatomegaly (p =
      0.012), and New York Heart Association functional class IV (p = 0.013).
      Multivariate analysis only selected preoperative icterus (p < 0.01) as being
      independently significantly related to hospital mortality. The hospital survivors
      were followed up for a median of 94 months. A complete follow-up was available
      for all patients except two for 30 months or more. At 30 months the only two
      significant parameters were the type of myocardial protection (p = 0.024) and the
      year of operation (before 1977 or after [precardioplegia era or after], p =
      0.011). There were 70 late deaths during the entire follow-up period. The
      univariate (log-rank statistics) incremental risk factor for late death was the
      type of tricuspid prosthesis (Smeloff-Cutter and Kay-Shiley versus St. Jude
      Medical versus bioprosthesis) (p = 0.04). A trend was observed for the type of
      operative myocardial protection (normothermia and coronary perfusion) (p = 0.06)
      and preoperative New York Heart Association functional class IV (p = 0.055).
      Actuarial survival was 74% at 60 months and 23.4% at 180 months. Cumulative
      follow-up added up to 1015 patient-years. In a more detailed analysis of the
      effect on survival of the type of tricuspid prosthesis, a significant difference
      was observed between the bioprostheses and some older mechanical prostheses
      (Smeloff-Cutter and Kay-Shiley) (p = 0.04) but not between the bioprostheses and
      the bileaflet valves (p = 0.15). When the follow-up period was stratified
      according to less than 7 years and more than 7 years of follow-up, no difference
      was observed for the first period, but for the late follow-up the new mechanical
      prostheses did better than the bioprostheses (p = 0.05), suggesting a degradation
      of the bioprostheses after 7 years and favoring mechanical prostheses for those
      patients with a good long-term prognosis.

PMID- 7564434
TI  - Allograft heart valve sterilization: a six-year in-depth analysis of a twenty
      five-year experience with low-dose antibiotics.
AB  - At the Prince Charles Hospital, from a 25-year experience with allograft heart
      valves (1969 to 1994), a 6-year analysis from March 1988 to August 1994 of the
      contamination rates and efficiency of a short-duration, low-dose antibiotic
      sterilization protocol was made. This analysis covered 642 collections and 680
      aortic and pulmonary valve implants. Tissue samples obtained at collection, valve
      trimming, postantibiotic incubation, and implant provided the raw data. At
      collection, valves retrieved in open mortuaries produced the highest
      contamination rate of 54%. Minimal exposure to antibiotics during transport and
      trimming reduced the contamination rate to 11% (p < 0.05). This was similar to
      the contamination rate at trimming for valves collected in the "sterile"
      operating room from multiorgan donors (12%). Antibiotic incubation at 37 degrees
      C for 6 hours reduced the contamination rate to 4% (p < 0.05). Only valves that
      showed no contamination at cryopreservation were implanted. However, at implant,
      resected tissue from valves that had been incubated in antibiotics showed a
      contamination rate of 3%, presumably from the theater environment, compared with
      15% (p < 0.05) for tissue from valves that had not been incubated. A residual
      antibiotic effect appears present at the time of implant in valves that have been
      incubated in antibiotics and may assist in the reduction of and resistance to
      infection in the immediate postoperative period. This is supported by the low
      incidence of endocarditis in the first 3 postoperative months. The simple and
      effective protocol of collection within 24 hours of death combined with low-dose
      antibiotic sterilization is sufficient to produce pathogen-free valves in the
      majority of cases (> 95%).

PMID- 7564435
TI  - Commissural dehiscence of Carpentier-Edwards mitral bioprostheses. Explant
      analysis and pathogenesis.
AB  - Manufacturing factors have seldom been implicated as a direct cause of structural
      deterioration of valvular bioprostheses; this phenomenon has generally been
      considered to be of a host-dependent origin. We analyzed the clinical and
      pathologic data from 12 Carpentier-Edwards mitral bioprostheses removed from 12
      patients because of severe dysfunction and showing detachment of the porcine
      aortic wall from the stent in one commissure or more. These 12 prostheses were
      part of a group of 92 such valves that were explanted and displayed structural
      deterioration. They belong to a population of 405 Carpentier-Edwards
      bioprostheses implanted in the mitral position in our institution between May
      1978 and November 1988. The patients included three men and nine women with a
      mean age of 54 +/- 13 years. One patient had a history of chronic renal failure,
      and two had systemic hypertension. Prosthesis sizes were 29, 31, and 33 mm (n = 4
      for each size). The models of the valves were 6625 (n = 8) and 6650 (n = 4). Mean
      duration of implantation of the prostheses was 99 +/- 27 months (52 to 136
      months) and did not differ depending on the model. There was no significant
      clustering of commissural detachments depending on valve size, year of
      implantation, or gender of the patient. No similar phenomenon was observed among
      76 explanted aortic Carpentier-Edwards bioprostheses with structural
      deterioration from a population of 441 valves implanted during the same time
      frame. Native porcine aortic roots (n = 5) and aortic Carpentier-Edwards
      bioprostheses explanted because of structural deterioration (n = 4) were used as
      controls for comparison. Macroscopic examination showed single commissural
      dehiscence in 10 patients and double in two. Radiology disclosed no or mild
      mineralization in eight valves and no calcium in the area of aortic wall
      dehiscence, except for heavily calcified valves. Light microscopy evidenced a
      significant thinning of the aortic wall at the paracommissural level of mitral
      bioprostheses (351 +/- 68 microns) compared with either aortic bioprostheses (526
      +/- 59 microns; p < 0.01) or control native porcine aortic roots (419 +/- 50
      microns; p < 0.01). No difference was found in terms of aortic wall thickness
      between detached (322 +/- 42 microns) and intact (366 +/- 74 microns) commissures
      in mitral bioprostheses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7564436
TI  - Dilation of the internal mammary artery by external and intraluminal papaverine
      application.
AB  - Three methods for prevention of perioperative spasm of the internal mammary
      artery were compared in 78 patients undergoing coronary artery bypass grafting.
      In group 1, internal mammary artery pedicles were divided distally, clamped, and
      placed under the upper sternum submerged in papaverine solution (1.5 mg/ml). In
      group 2, as in group 1 but before clamping, 2 ml of heparinized blood with 1.5
      mg/ml papaverine added was injected into the vessel lumen. In group 3 treatment
      was as in group 2, but heparinized blood with papaverine was injected a second
      time just before extracorporeal bypass was begun. In a univariate analysis free
      flow from dilated internal mammary arteries was not significantly different among
      the groups (group 1, 58 ml/min; group 2, 82 ml/min; group 3, 68 ml/min; p < 0.1).
      When free flow from dilated internal mammary arteries was the dependent variable
      in a regression analysis, the use of intraluminal papaverine, high blood pressure
      during flow measurement, and high initial blood flow were predictors of high flow
      (all p < 0.01). Morphometric measurements on the resected distal portion of the
      dilated internal mammary arteries disclosed less folding of the internal elastic
      lamina and a larger luminal area in groups 2 and 3 compared with respective
      findings in group 1 (1.21 mm2 and 1.42 mm2 versus 0.77 mm2; p < 0.02). Mechanical
      vessel wall injury occurred in 8 of 52 internal mammary arteries treated with
      intraluminal papaverine. Intraluminal papaverine solution injected once or twice
      in addition to external papaverine exposure therefore provides a better blood
      flow rate and distal dilation than mere submersion in papaverine solution, but at
      a considerable risk of mechanical wall injury.

PMID- 7564437
TI  - Magnetic resonance velocity vector mapping of blood flow in thoracic aortic
      aneurysms and grafts.
AB  - Magnetic resonance imaging with multidirectional cine velocity mapping was used
      to study relationships between aortic blood flow patterns and the geometry of
      thoracic aortic aneurysms and grafts. Ten patients with 13 thoracic aortic
      aneurysms, single or multiple, or grafts (4) participated in the study. The
      causes of disease were atherosclerosis (4), Marfan's syndrome (2), trauma (1),
      and unknown (1), and there were two dissections. Spin-echo imaging and cine
      velocity mapping in 10 mm thick slices with vertical and horizontal velocity
      encoding were done. Maps of the two velocity components were processed into
      multiple computer-generated streaks whose orientation and length corresponded to
      velocity vectors in the chosen plane. The dynamic arrow maps were compared with
      previously reported aortic arrow maps from normal subjects. The forward flow
      occupied the entire lumen in the normal aorta in systole and small vortices were
      only present in the sinuses of Valsalva. Atherosclerotic aneurysms in the
      ascending aorta were located at the anterior right and had oblique, eccentric jet
      flows that created a large secondary vortex in the aneurysm. Patients with
      Marfan's syndrome had a central jet and two large vortices, one on each side. All
      other aneurysms, dissections, and grafts had irregular flows and vortices not
      seen in normal subjects. Magnetic resonance imaging with multidirectional
      velocity mapping is a powerful noninvasive tool to assess morphologic features
      and disturbed blood flow in aortic aneurysms and grafts. Recognizably altered
      flow patterns were found to be associated with altered vessel geometry. The
      significance of this requires further investigation.

PMID- 7564439
TI  - Extracorporeal membrane oxygenation as an adjunct treatment for primary graft
      failure in adult lung transplant recipients.
AB  - Primary graft failure is a catastrophic event in lung transplantation. Failure is
      characterized by profound abnormalities of gas exchange that are frequently
      unresponsive to alterations in mechanical ventilation. This condition can be
      fatal and, if less severe, is usually associated with significant permanent
      damage to the allograft. We report the use of extracorporeal membrane oxygenation
      as a means to support lung transplant recipients with severe graft failure. Since
      1991, extracorporeal membrane oxygenation has been used on 17 occasions for the
      temporary support of 16 adult lung transplant recipients. All patients met or
      exceeded standard National Institutes of Health guidelines for institution of
      extracorporeal membrane oxygenation. Nine double lung, six single lung, and one
      heart-lung recipients were supported for 1 to 12 days (mean 4.6 +/- 2.2 days).
      Extracorporeal membrane oxygenation was instituted early, within 7 days of
      transplantation, in ten patients. Eight early patients (80%) were successfully
      weaned from extracorporeal membrane oxygenation. Seven of ten (70%) patients were
      long-term survivors, and five of the seven had normal lung function. In
      comparison, there were no survivors among six recipients placed on extracorporeal
      membrane oxygenation for late (> or = 7 days) graft dysfunction. Extracorporeal
      membrane oxygenation is a lifesaving adjunct in recipients with acute graft
      failure after lung transplantation. Ischemia-reperfusion injury and acute graft
      dysfunction after lung transplantation can be successfully reversed with early
      aggressive intervention.

PMID- 7564438
TI  - Xanthine oxidase inactivation attenuates postocclusion shock after descending
      thoracic aorta occlusion and reperfusion in rabbits.
AB  - "Declamping shock" is observed after aortic crossclamping, with hypovolemia,
      hypotension, and metabolic acidemia invariably present. We hypothesized that
      oxidants derived from xanthine oxidase influence the resuscitative interventions
      required to maintain baseline hemodynamic and acid-base status after aortic
      occlusion and reperfusion in rabbits. We also hypothesized that inactivation of
      xanthine oxidase with sodium tungstate could reduce systemic injury as assessed
      by the release of lactate dehydrogenase and alkaline phosphatase. To test these
      hypotheses, we established aortic occlusion in rabbits (n = 10, standard diet; n
      = 8, tungstate diet) for 40 minutes by inflation of a 4F Fogarty catheter in the
      descending thoracic aorta followed by 2 hours of reperfusion. Sham-operated
      rabbits (n = 10, standard diet; n = 9, tungstate diet) served as controls.
      Tungstate-pretreated rabbits required significantly less Ringer's solution (28%),
      phenylephrine (68%), and sodium bicarbonate (30%) during reperfusion (p < 0.005).
      Lactate dehydrogenase and alkaline phosphatase release during reperfusion was
      significantly attenuated by tungstate pretreatment (p < 0.05). Tungstate
      pretreatment resulted in plasma xanthine oxidase activities significantly lower
      than those in the sham group administered a standard diet (p = 0.007).
      Resuscitation requirements and systemic injury were reduced by inactivation of
      xanthine oxidase in a rabbit model that simulates the situation of human thoracic
      aorta operations.

PMID- 7564440
TI  - Experimental tracheal allograft revascularization and transplantation.
AB  - The feasibility of tracheal allotransplantation with a fascial vascular carrier
      was examined in three groups with varied dose sequences of immunosuppression. A
      control group (group 1) received no medication. The three experimental groups
      were given daily cyclosporine intramuscular doses of 5 mg/kg (group 2), 5 mg/kg
      plus 3 mg/kg methylprednisolone (Solu-Medrol) (group 3), and 10 mg/kg (group 4)
      for 6 weeks or until death. Grafts were assessed by silicone dye infusion of the
      artery of the fascial flap to examine their microcirculation and by quantitative
      histologic study. Group 1 evidenced complete rejection after a heterotopic
      revascularization period of 14 days. The allografts of the experimental groups
      remained viable after 14 days of revascularization and could be transplanted
      orthotopically after this period. After transplantation, the viability of group 2
      tracheas was unpredictable with changes ranging from mild to complete rejection.
      Group 3 evidenced well-preserved transplant viability with infection-induced
      necrosis at the anastomoses caused by the corticosteroid component. All group 4
      animals survived the follow-up period with normal allograft viability.
      Cyclosporine in a dosage of 10 mg/kg per day can effectively suppress the immune
      response after transplantation of vascularized tracheal allografts. This
      experimental model will allow future studies to examine airway wall
      immunogenicity.

PMID- 7564441
TI  - Extracellular and standard University of Wisconsin solutions provide equivalent
      preservation of myocardial function.
AB  - The deleterious effect of hyperkalemic cardioplegic solutions on coronary
      endothelium has been documented and has also been demonstrated with University of
      Wisconsin solution. We evaluated a new extracellular University of Wisconsin
      formulation for efficacy in heart preservation. Six neonatal piglet hearts were
      arrested with and stored in the standard intracellular University of Wisconsin
      solution (group 1: K+ 125 mEq/L, Na+ 29 mEq/L). Six piglet hearts were preserved
      for 24 hours with an extracellular University of Wisconsin solution that differed
      only in the concentrations of potassium and sodium (group 2: K+ 25 mEq/L, Na+ 129
      mEq/L). Hearts underwent modified reperfusion with leukocyte-depleted aspartate
      glutamate enriched blood cardioplegic solution followed by conversion to a left
      sided working mode on a Langendorff circuit with perfusion from a support pig.
      Stroke work index was calculated at left ventricular end-diastolic pressures of
      3, 6, 9, and 12 mm Hg. Sixty minutes after reperfusion, there was no significant
      difference in stroke work index between group 1 (16.4 +/- 1.9 x 1000 erg/gm) and
      group 2 (15.3 +/- 2.7 x 1000 erg/gm). There was also no significant difference in
      high-energy phosphate stores or myocardial water content between the two groups.
      Extracellular University of Wisconsin solution provides myocardial preservation
      equivalent to standard University of Wisconsin solution while preventing exposure
      of coronary endothelium to high levels of potassium, which justifies its use in
      clinical heart transplantation.

PMID- 7564442
TI  - Desensitization of myocardial beta-adrenergic receptors and deterioration of left
      ventricular function after brain death.
AB  - Brain death often results in a series of hemodynamic alterations that complicate
      the treatment of potential organ donors before transplantation. The deterioration
      of myocardial performance after brain death has been described; however, the
      pathophysiologic process of the myocardial dysfunction that occurs after brain
      death has not been elucidated. This study was designed to analyze the function of
      the myocardial beta-adrenergic receptor and the development of left ventricular
      dysfunction in a porcine model of experimental brain death. Analysis of the beta
      receptor included determination of receptor density and adenylate cyclase
      activity after stimulation independently at the receptor protein, the G protein,
      and the adenylate cyclase moiety. Myocardial beta-receptor density did not change
      after the induction of brain death. A decrease in stimulated adenylate cyclase
      activity was observed within the first hour after brain death at the level of the
      beta-receptor, the G protein, and the adenylate cyclase moiety, which suggests
      the occurrence of rapid desensitization of beta-receptor function. Significant
      deterioration of myocardial performance also occurred within the first hour after
      brain death, represented by a decrease in preload-recruitable stroke work
      compared with the baseline value. The deterioration of myocardial performance
      after brain death correlates temporally with desensitization of the myocardial
      beta-receptor signal transduction system. The mechanism of impairment appears to
      be localized to the adenylate cyclase moiety itself.

PMID- 7564443
TI  - Protection against injury during ischemia and reperfusion by acadesine
      derivatives GP-1-468 and GP-1-668. Studies in the transplanted rat heart.
AB  - BACKGROUND: Acadesine (AICAr: 5-amino-4-imidazole carboxamide riboside) has been
      shown to afford sustained protection against injury during ischemia and
      reperfusion. The present studies used the heterotopically transplanted rat heart
      to assess the protective properties of two new acadesine analogs: GP-1-468 and GP
      1-668. METHODS AND RESULTS: Hearts were excised, arrested with a 2-minute
      infusion of cardioplegic solution, and subjected to 4 hours of global ischemia
      (20 degrees C) with cardioplegic reinfusion for 2 minutes every 30 minutes. The
      hearts were then transplanted (1 hour of additional ischemia) into the abdomens
      of recipient rats and reperfused in situ for 30 minutes or 24 hours. The hearts
      were then excised, perfused aerobically for 20 minutes, and contractile function
      was assessed. GP-1-468 or GP-1-668 was administered to donor rats (20 mg/kg
      intravenously, 30 minutes before excision). They were also added to the
      cardioplegic solution (10 mumol/L for GP-1-468, 5 mumol/L for GP-1-343, the
      active metabolite of GP-1-668) and were also given to recipient rats (20 mg/kg
      intravenously, 30 minutes before transplantation, so that the drugs were present
      during reperfusion). Nine groups of hearts were studied. Three groups of studies
      were carried out (n = 24 transplants for each group). The first group of hearts
      was reperfused for 30 minutes, the second group was reperfused for 24 hours, and
      the third group was transplanted but not reperfused; instead, they were frozen at
      the end of 5 hours of ischemia and taken for metabolite analysis. Within each
      group were three subgroups (n = 8 per group) receiving GP-1-468, GP-1-668, or
      saline solution. In the 30-minute reperfusion group the recoveries of left
      ventricular developed pressure were 88 +/- 4, 87 +/- 7, and 50 +/- 9 mm Hg,
      respectively (p < 0.05 versus saline-treated controls); left ventricular volumes
      (recorded at 12 mm Hg) were 112 +/- 20, 132 +/- 28, and 41 +/- 9 microliters,
      respectively (p < 0.05 versus saline-treated controls), and coronary flows were
      13.1 +/- 0.7, 13.4 +/- 1.0, and 9.9 +/- 0.5 ml/min, respectively (p < 0.05 versus
      saline-treated controls). In addition to improving functional recovery, the two
      analogs increased the tissue content of adenosine at the end of the ischemic
      period (5.4 +/- 0.6 and 7.3 +/- 0.5 mumol/gm dry weight, respectively, versus 2.7
      +/- 0.4 mumol/gm dry weight in the saline-treated controls; p < 0.05); however,
      they did not influence adenosine triphosphate or its catabolites. In the 24-hour
      reperfusion group the corresponding values were 77 +/- 6 and 88 +/- 6 versus 35
      +/- 4 mm Hg for left ventricular developed pressure (p < 0.05), 111 +/- 9 and 121
      +/- 11 versus 41 +/- 8 microliters for left ventricular volume (p < 0.05), and
      13.7 +/- 0.7 and 13.0 +/- 0.6 versus 11.7 +/- 0.7 ml/min for coronary flow (no
      significant difference). Thus both analogs afforded an early and comparable
      degree of protection of contractile function that was sustained even after 24
      hours of reperfusion. CONCLUSIONS: Both GP-1-468 and GP-1-668 increase the rate
      and extent of early postischemic recovery, and this protection is sustained for
      at least 24 hours. These beneficial actions were associated with an increase of
      the tissue content of adenosine during ischemia, but they appeared to be
      independent of the status of the high-energy metabolism.

PMID- 7564444
TI  - Experimental carinal autotransplantation and allotransplantation.
AB  - Grafting is required when a primary reconstruction of a carinal defect is not
      feasible. A series of experiments in 21 dogs was conducted to assess the
      possibility of carinal reconstruction with the use of carinal autografts and
      allografts, with or without omentopexy. Carinal autograft transplantations were
      done without omentopexy in group A (n = 6) and with omentopexy in group B (n =
      6). In group C (n = 9), carinal allograft transplantations were done with
      omentopexy and FK 506 was administered after operation. Survival of grafts was
      seen in 50% of group A, 83% of group B, and 44% of group C dogs. Postoperative
      bronchoscopy revealed inflammatory changes in the surviving grafts; the changes
      resolved more rapidly in the dogs with omentopexy than in the dogs without
      omentopexy. These experiments suggest that omentopexy is an effective method of
      facilitating survival and healing in carinal grafts and that carinal
      reconstruction with carinal allografts with FK 506 is feasible.

PMID- 7564445
TI  - Regional generation of free oxygen radicals during cardiopulmonary bypass in
      children.
AB  - Studies on free radical generation during cardiopulmonary bypass have focused
      mainly on the heart and the lungs. However, low pumping pressure, nonpulsatile
      perfusion, and hypothermia affect the entire circulation, resulting in decreased
      splanchnic blood flow, increased intestinal permeability, and endotoxemia. To
      evaluate regional phenomena, we studied 16 children undergoing cardiopulmonary
      bypass. Free radical production, granulocyte activation, and hypoxanthine
      metabolism were assessed separately in the circulations drained by the inferior
      and superior venae cavae, as well as in the oxygenator. Three minutes after the
      onset of cardiopulmonary bypass, significant gradients between the inferior vena
      cava and the arterial line of the oxygenator existed in malondialdehyde (+0.60 +/
      0.12 mumol/L, lactoferrin (+18.21 +/- 7.65 micrograms/L), myeloperoxidase
      (+53.75 +/- 16.50 micrograms/L), hypoxanthine (-0.62 +/- 0.15 mumol/L), and urate
      (+8.87 +/- 4.03 mumol/L). These gradients decreased in parallel with decreasing
      body temperature. Except for a transient gradient in malondialdehyde at 3 minutes
      after the onset of cardiopulmonary bypass (+0.23 +/- 0.08 mumol/L), no changes
      were detected between the superior vena cava and the arterial line. In the
      oxygenator, granulocyte activation was observed only after aortic declamping. We
      conclude that during cardiopulmonary bypass, significant free radical generation,
      granulocyte activation, hypoxanthine elimination, and urate production take place
      in the region drained by the inferior vena cava. In the oxygenator, granulocyte
      activation occurs only after aortic declamping.

PMID- 7564446
TI  - Tissue oxygenation with graded dissolved oxygen delivery during cardiopulmonary
      bypass.
AB  - BACKGROUND: Intravascular perfluorochemical emulsions together with a high oxygen
      tension may increase the delivery of dissolved oxygen to useful levels. The
      hypothesis of this study is that increasing the dissolved oxygen content of blood
      with incremental doses of a perfluorochemical emulsion improves tissue
      oxygenation during cardiopulmonary bypass in a dose-related fashion. METHODS AND
      RESULTS: Oxygen utilization was studied in a profoundly anemic canine model of
      hypothermic cardiopulmonary bypass. Forty-two dogs underwent normovolemic
      hemodilution to a hematocrit of 15.8% +/- 0.6% (mean +/- standard error of the
      mean). Cardiopulmonary bypass was begun and resulted in a hematocrit of 9.4% +/-
      0.6%. A standard priming solution was used in the control group (n = 12), and the
      test groups received 1.35 gm perfluorochemical.kg-1 (n = 10 dogs), 2.7 gm
      perfluorochemical.kg-1 (n = 10 dogs), or 5.4 gm perfluorochemical.kg-1 (n = 10
      dogs) through the venous return cannula. Each animal underwent a series of
      randomized pump flows (0.25, 0.5, 1.0, 1.5, 2.0, and 3.0 L.min-1.m-2) at 32
      degrees C. After the randomized flows were completed at 32 degrees C, the
      temperature was raised to 38 degrees C and cardiopulmonary bypass was
      discontinued. Mortality from cardiac failure on separation from cardiopulmonary
      bypass was 42% in the control group and 20% in perfluorochemical-treated groups.
      The mean perfluorochemical dose was higher in survivors than in nonsurvivors (2.9
      +/- 0.4 versus 1.3 +/- 0.5 gm perfluorochemical.kg-1; p < 0.05). No differences
      in oxygen consumption or transbody lactate gradient were found between groups
      during cardiopulmonary bypass. Analysis of mixed venous oxygen tension (a
      surrogate measure for tissue oxygenation) as a function of cardiopulmonary bypass
      flow normalized to body surface area showed that the control group had
      significantly lower mixed venous oxygen tension (p < 0.05) than the
      perfluorochemical emulsion-treated groups. Furthermore, the differences were
      related to the perfluorochemical emulsion dose. These differences in mixed venous
      oxygen tension continued after termination of cardiopulmonary bypass. The
      coronary sinus oxygen tension and cardiac arterial-venous oxygen content
      differences during and after cardiopulmonary bypass were similar among the
      control and perfluorochemical emulsion-treated animals. Dissolved oxygen
      consumption during and after cardiopulmonary bypass was calculated. Dissolved
      oxygen consumption increased in the perfluorochemical-treated animals in a
      perfluorochemical dose-related manner and was significantly higher in
      perfluorochemical-treated animals than in the control animals (p < 0.05).
      CONCLUSIONS: Graded increases in mixed venous oxygen tension during
      cardiopulmonary bypass were observed in response to graded increases in the
      dissolved oxygen delivery. These data suggest that enhancing oxygenation with
      perfluorochemical-dissolved oxygen is an effective temporary substitute for the
      use of hemoglobin-bound oxygen during cardiopulmonary bypass. Perfluorochemical
      dissolved oxygen may be particularly beneficial in the setting of multiple
      hypoxic stresses.

PMID- 7564447
TI  - The relationship between intelligence and duration of circulatory arrest with
      deep hypothermia.
AB  - A total of 114 children (51 with tetralogy of Fallot, 30 with transposition of
      the great arteries, and 33 with ventricular septal defect) who had these defects
      repaired with the use of deep hypothermia and circulatory arrest were assessed
      for intellectual and neuropsychologic function at an average of 9 to 10 years
      after the operation. Children with preoperative intellectual handicaps or
      postoperative neurologic complications were excluded. These children were
      compared with 54 who had atrial septal defects repaired with the use of
      cardiopulmonary bypass. The only significant difference in the neuropsychologic
      measures was that the bypass group had reaction times 2 to 3 seconds shorter on
      average than those of the hypothermic circulatory arrest group. Although there
      was no significant difference in intelligence quotient between the groups, a
      relationship between intelligence quotient and arrest time was found. Regression
      analysis of intelligence quotient against duration of arrest showed a significant
      decrease in intelligence quotient with increasing arrest time (slope = -0.36; p =
      0.002; 95% confidence interval, -0.59, -0.14) indicating a decrease of 3 to 4
      intelligence quotient points for each extra 10 minutes of arrest time. It appears
      that deep hypothermia with circulatory arrest for cardiac operations in children
      does not fully protect the brain, with a linear relationship existing between the
      amount of impairment and the duration of circulatory arrest.

PMID- 7564448
TI  - Left ventricular mechanoenergetics during asynchronous left atrial-to-aortic
      bypass. Effects of pumping rate on cardiac workload and myocardial oxygen
      consumption.
AB  - The purpose of this study was to analyze left ventricular energetics during
      asynchronous, pulsatile left atrial to aortic bypass in the failing heart with
      the use of the pressure-volume relationship. In 12 anesthetized Holstein calves
      (body weight 94 +/- 7 kg), 10 microns microspheres (3.3 x 10(7) +/- 1.1 x
      10(7)/100 gm left ventricular weight) were injected into the left main coronary
      artery to induce heart failure. Baseline left ventricular end-systolic elastance
      significantly decreased from 7.9 +/- 0.7 to 5.5 +/- 0.4 mm Hg/ml 100 gm left
      ventricular weight. Left ventricular pressure was measured with a micromanometer,
      and ultrasonic dimension transducers measured left ventricular orthogonal
      diameters. Ellipsoidal geometry was used to calculate simultaneous left
      ventricular volume. End-systolic elastance, pressure-volume area, external work,
      potential energy, and myocardial oxygen consumption were analyzed during steady
      state contractions. After pre-pulsatile left atrial to aortic bypass measurements
      were taken, the measurements were repeated during asynchronous pulsatile left
      atrial to aortic bypass at the maximal pumping rate (69 +/- 13 beats/min) termed
      100%, and then 80%, 60%, and 40% of the maximal pumping rate in the full to empty
      mode. With increases in pumping rate, pressure-volume area and external work
      proportionally decreased, whereas potential energy remained unchanged except for
      100% of maximal pumping rate. Pressure-volume area correlated linearly with
      myocardial oxygen consumption during asynchronous pulsatile left atrial to aortic
      bypass (r = 0.971). As a result, pumping rate correlated linearly with
      conservation of myocardial oxygen consumption (r = 0.998). In conclusion,
      decreased pressure-volume area accounts for the reduction in myocardial oxygen
      consumption during asynchronous pulsatile left atrial to aortic bypass.
      Conservation of myocardial oxygen consumption is mainly attributed to the
      reduction of external work.

PMID- 7564449
TI  - Adequate distribution of warm cardioplegic solution.
AB  - Seventy-five patients undergoing coronary artery bypass grafting were randomized
      to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of
      warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution.
      Myocardial oxygen utilization, lactate and acid metabolism, and adenine
      nucleotides and their degradation products were measured during the operation and
      cardiac function was assessed postoperatively. Warm retrograde delivery of
      cardioplegic solution increased lactate and acid release during cardioplegia and
      reperfusion, decreased left ventricular adenosine triphosphate concentrations,
      and reduced the washout of adenine nucleotide degradation products from both left
      and right ventricles. Warm antegrade delivery of cardioplegic solution resulted
      in less lactate and acid release during cardioplegia but more lactate accumulated
      in the territory of the left anterior descending artery during the crossclamp
      period. Intermittent antegrade delivery of the cardioplegic solution during
      combination cardioplegia washed out lactate and acid, which suggested
      inhomogeneous delivery of the cardioplegic solution during continuous retrograde
      cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in
      the left ventricle and resulted in the best postoperative left and right
      ventricular function. A combination of intermittent antegrade and continuous
      retrograde delivery of cardioplegic solution provided better myocardial
      protection than either antegrade or retrograde delivery of cardioplegic solution
      alone.

PMID- 7564450
TI  - Hemostatic function of aspirin-treated platelets vulnerable to cardiopulmonary
      bypass. Altered shear-induced pathway.
AB  - The impaired hemostasis of aspirin-treated patients is an annoying problem during
      and after cardiopulmonary bypass. The hemostatic function of platelets comprises
      two mechanisms: the shear-induced and the cyclooxygenase pathways. Because the
      latter is inhibited in aspirin-treated patients, the hemostatic function depends
      mainly on the former pathway. To investigate the effect of cardiopulmonary bypass
      on the shear-induced pathway, a double-blind study of preoperative aspirin
      treatment (325 mg) and placebo was conducted in 40 patients undergoing coronary
      artery bypass grafting. Postoperative blood loss was higher in the aspirin
      treated patients than in the placebo-treated patients (p < 0.05). The shear
      induced hemostasis was monitored by the in vitro bleeding test (Thrombostat),
      which mimics bleeding through an injured arteriole. The shear-induced pathway of
      aspirin-treated platelets was not affected before cardiopulmonary bypass, but it
      was impaired more during the operation (p < 0.01) and remained worse afterward (p
      < 0.05), compared with that of placebo-treated platelets. The inhibitory effects
      of aspirin on thromboxane production and on collagen-induced platelet aggregation
      remained throughout the operation. In aspirin-treated platelets, the aggregation
      capacity induced by adenosine diphosphate was inhibited before the operation (p <
      0.05) and showed substantial recovery during the operation (p < 0.05). These
      results suggest that the shear-induced pathway of aspirin-treated platelets is
      more vulnerable to cardiopulmonary bypass than the pathway in normal platelets
      and causes severe impairment of hemostasis afterward.

PMID- 7564451
TI  - Gut mucosal ischemia during normothermic cardiopulmonary bypass results from
      blood flow redistribution and increased oxygen demand.
AB  - Impaired gut mucosal perfusion has been reported during cardiopulmonary bypass.
      To better define the adequacy of gut blood flow and oxygenation during
      cardiopulmonary bypass, we measured overall gut blood flow and ileal mucosal flow
      and their relationship to mucosal pH, mesenteric oxygen delivery and oxygen
      consumption in immature pigs (n = 8). Normothermic, noncross-clamped, right
      atrium-to-aorta cardiopulmonary bypass was maintained at 100 ml/kg per minute for
      120 minutes. Animals were instrumented with an ultrasonic Doppler flow probe on
      the superior mesenteric artery, a mucosal laser Doppler flow probe in the ileum,
      and pH tonometers in the stomach, ileum, and rectum. Radioactive microspheres
      were injected before and at 5, 60, and 120 minutes of cardiopulmonary bypass for
      tissue blood flow measurements. Overall gut blood flow significantly increased
      during cardiopulmonary bypass as evidenced by increases in superior mesenteric
      arterial flow to 134.1% +/- 8.0%, 137.1% +/- 7.5%, 130.3% +/- 11.2%, and 130.2%
      +/- 12.7% of baseline values at 30, 60, 90, and 120 minutes of bypass,
      respectively. Conversely, ileal mucosal blood flow significantly decreased to
      53.6% +/- 6.4%, 49.5% +/- 6.8%, 58.9% +/- 11.6%, and 47.8% +/- 10.0% of baseline
      values, respectively. Blood flow measured with microspheres was significantly
      increased to proximal portions of the gut, duodenum and jejunum, during
      cardiopulmonary bypass, whereas blood flow to distal portions, ileum and colon,
      was unchanged. Gut mucosal pH decreased progressively during cardiopulmonary
      bypass and paralleled the decrease in ileal mucosal blood flow. Mesenteric oxygen
      delivery decreased significantly from 67.0 +/- 10.0 ml/min per square meter at
      baseline to 42.4 +/- 4.6, 44.9 +/- 3.5, 46.0 +/- 3.6, and 42.9 +/- 3.9 ml/min per
      square meter at 30, 60, 90, and 120 minutes of bypass. Despite the decrease in
      mesenteric oxygen delivery, mesenteric oxygen consumption increased progressively
      from 10.8 +/- 1.4 ml/min per square meter at baseline to 13.4 +/- 1.2, 15.9 +/-
      1.2, 16.7 +/- 1.4, and 16.6 +/- 1.54 ml/min per square meter, respectively. We
      conclude that gut mucosal ischemia during normothermic cardiopulmonary bypass
      results from a combination of redistribution of blood flow away from mucosa and
      an increased oxygen demand.

PMID- 7564452
TI  - Reduced complement activation and improved postoperative performance after
      cardiopulmonary bypass with heparin-coated circuits.
AB  - A randomized controlled trial that involved 30 patients undergoing elective
      coronary artery bypass grafting was done to determine the effect of heparin
      coated circuits and full heparinization on complement activation, neutrophil
      mediated inflammatory response, and postoperative clinical recovery. Peak
      concentrations of terminal complement complex were 38% lower (p = 0.004) in 15
      patients treated with heparin-coated circuits (median 775 micrograms/L,
      interquartile range 600 to 996) compared with those in 15 patients treated with
      uncoated circuits (median 1249 micrograms/L, interquartile range 988 to 1443).
      Although no significant intergroup differences in concentrations of
      polymorphonuclear neutrophil elastase were found, a positive correlation (rs =
      0.74, p < 0.0007) was calculated between peak concentrations of terminal
      complement complex and polymorphonuclear neutrophil elastase. Differences in
      patient recovery were analyzed with use of a score composed of fluid balance,
      postoperative intubation time, and the difference between rectal temperature and
      skin temperature. The score was significantly lower in patients treated with
      heparin-coated circuits (p = 0.03), whereas its components showed no intergroup
      significance. We conclude that the use of heparin-coated circuits with full
      systemic heparinization results in improved biocompatibility, as assessed by
      complement activation, and leads to an improved postoperative recovery of the
      patient.

PMID- 7564453
TI  - Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic
      acid. Double-blind, randomized clinical trial.
AB  - This prospective, double-blind, randomized trial assessed the effectiveness of
      high-dose tranexamic acid given in the preoperative period on blood loss in
      patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled
      to undergo cardiac operations with cardiopulmonary bypass were randomized into
      three groups of equal size. The first group received 10 gm of tranexamic acid
      intravenously over 20 minutes before sternotomy and a placebo infusion over 5
      hours. The second group received 10 gm of tranexamic acid over 20 minutes and
      then another 10 gm infused intravenously over 5 hours. The control group received
      a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline
      solution). The blood loss after the operation was measured at 6 hours and 24
      hours. The homologous blood and blood products given during and up to 48 hours
      after operation were recorded. Eighteen percent of the control group patients
      shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic
      acid groups. Patients who shed more than 750 ml blood required 93% more red blood
      cell transfusions than patients without excessive bleeding. Tranexamic acid (10
      gm) given intravenously in the period before cardiopulmonary bypass reduced blood
      loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid
      infusion (10 gm over 5 hours) did not reduce bleeding further. There was no
      difference in the coagulation profile before operation between patients with and
      without excessive bleeding. However, coagulation tests done in the postoperative
      period indicated ongoing fibrinolysis and platelet dysfunction in patients with
      excessive bleeding.

PMID- 7564455
TI  - The rapid transformation of hyperthyroidism to hypothyroidism complicated by
      myasthenia gravis.

PMID- 7564454
TI  - Complications of extracorporeal life support systems using heparin-bound
      surfaces. The risk of intracardiac clot formation.
AB  - Extracorporeal life support with heparin-coated extracorporeal membrane
      oxygenation circuits are being used with increased frequency in patients who have
      cardiogenic shock. We report our experience in 30 patients with cardiogenic
      shock, looking specifically at the complications associated with this form of
      life support. Thirty patients with a mean age of 46.5 +/- 16.6 years received
      extracorporeal life support for a mean of 62.8 +/- 41.1 hours (range 0.5 to 159
      hours). Twenty-three patients had postcardiotomy cardiogenic shock, five had
      acute myocardial infarction, and one each had acute cardiac deterioration after a
      balloon coronary angioplasty and another after pulmonary artery balloon
      angioplasty. Peripheral (femoral vein to femoral artery) cannulation was used in
      24 patients. Limb ischemia developed in 21 patients (70%), renal failure in 17
      patients (57%), oxygenator failure requiring change in 13 patients (43%),
      bleeding requiring reexploration in 12 (40%), and infection in 9 patients (30%).
      Transesophageal echocardiography revealed intracardiac thrombus formation in 6
      patients (20%) and clot was visualized grossly in the pump head in 2 patients
      (6%) necessitating pump-head change. Nine patients (30%) were discharged home. We
      conclude that the use of heparin-coated extracorporeal life support without
      systemic heparinization, especially after protamine has been used to reverse
      systemic heparinization in patients having postcardiotomy cardiogenic shock, may
      be dangerous. Extracorporeal life support has introduced new complications unique
      to itself specifically limb ischemia, oxygenator failure, and pump-head thrombus.

PMID- 7564456
TI  - Pulmonary atresia, intact ventricular septum, and major aortopulmonary
      collaterals: morphogenetic and surgical implications.

PMID- 7564457
TI  - Tumor dissemination after thoracoscopic resection for lung cancer.

PMID- 7564458
TI  - Transventricular mitral valve dilator: an improved design concept.

PMID- 7564459
TI  - Transfer of the posterior tricuspid leaflet and chordae for mitral valve repair.

PMID- 7564460
TI  - Successful treatment of life-threatening acute reperfusion injury after lung
      transplantation with inhaled nitric oxide.

PMID- 7564461
TI  - Pseudoaneurysm of the brachiocephalic artery caused by blunt chest trauma.

PMID- 7564462
TI  - Modified hemi-Fontan operation and subsequent nonsurgical Fontan completion.

PMID- 7564463
TI  - Reconstruction of the pulmonary artery by a conduit of autologous pericardium.

PMID- 7564464
TI  - Enoximone in internal mammary artery hypoperfusion.

PMID- 7564465
TI  - Narrowing of the aortic anulus in valve-sparing annuloaortic grafting.

PMID- 7564466
TI  - Nonsyndrome familial atrial myxoma in two generations.

PMID- 7564467
TI  - Perioperative use of carbon dioxide production in cardiac surgery.

PMID- 7564468
TI  - Characteristic biological features of human megakaryoblastic leukaemia cell
      lines.
AB  - Both normal and leukaemic human megakaryocytopoiesis are stimulated by several
      cytokines, including stem cell factor, granulocyte-macrophage colony stimulating
      factor (GM-CSF), interleukin-3, GM-CSF/interleukin-3 fusion protein, interleukin
      6, interleukin-11, basic fibroblast growth factor and thrombopoietin, but are
      inhibited by tumour necrosis factor-alpha, platelet factor 4, beta
      thromboglobulin, thrombin, interleukin-4, interferon-alpha and interferon-gamma.
      Human megakaryoblastic leukaemia cell lines have common biological features,
      including high expression of the megakaryocytic specific antigen: CD41; high
      expression of the early myeloid antigens: CD34 and CD33; constitutive expression
      of interleukin-6 and platelet-derived growth factor; complex karyotype picture;
      expression of c-kit: the stem cell factor receptor; growth-dependency or 
      stimulation by stem cell factor, interleukin-3 and/or GM-CSF; megakaryoblastic
      differentiation by phorbol-myristate-acetate; and in vivo tumorigenicity in mice
      is associated with marked fibrosis. Only a few agents including phorbol-myristate
      acetate; vitamin D3, interferon-alpha, interferon-beta 2, erythropoietin and
      thrombin have been reported to induce megakaryocytic differentiation in the human
      megakaryoblastic leukaemia cells.

PMID- 7564469
TI  - Acute leukemic transformation of myelodysplastic syndrome--immunophenotypic,
      genotypic, and cytogenetic studies.
AB  - The clinical and biological characteristics of myelodysplastic syndrome (MDS) in
      acute leukemic transformation were studied in 23 patients. All had myeloid
      transformation according to FAB criteria, but coexpression of lymphoid-associated
      antigens was detected in five of the 20 patients who underwent an
      immunophenotypic study. Rearrangement of the immunoglobulin heavy chain gene was
      also observed in one of the five patients who coexpressed lymphoid markers and
      that of the T-cell receptor beta chain gene in another one. None had pure
      lymphoid transformation. Clonal chromosomal abnormalities were noted in 12 (63%)
      of the 19 patients who underwent cytogenetic study, most commonly - 7 (six
      patients or 32%). In the 18 patients who underwent serial analyses both at MDS
      diagnosis and at acute transformation, seven (39%) underwent karyotypic
      evolution. The most common new or additional aberrations were +8 and +21. N-ras
      gene mutation was detected in two of the nine patients at acute leukemic
      transformation. The median interval from diagnosis of MDS to onset of acute
      transformation was 10 months (1-36 months). Patients with a normal karyotype at
      diagnosis had a significantly longer chronic phase duration than those with
      chromosomal abnormalities (median of 20 months vs. 5 months). However, all had a
      short survival time after diagnosis of acute leukemia, whether chromosomal
      anomalies were present or not.

PMID- 7564470
TI  - Effects of vitamin A on survival in patients with chronic myelogenous leukemia: a
      SWOG randomized trial.
AB  - A national cooperative group trial was conducted in 153 patients with chronic
      myelogenous leukemia (CML) in chronic phase treated with oral pulse busulfan to
      determine if oral vitamin A can increase the time to blast crisis and enhance
      survival of patients. Patients diagnosed within 1 year and in the chronic phase
      of CML were randomized to receive oral pulse busulfan or the alkylator plus
      continuous oral vitamin A. Distributions of clinical progression and overall
      survival were estimated using the method of Kaplan and Meier. Associations of
      these endpoints with treatment and other patient characteristics were analyzed
      using the proportional hazards regression method of Cox. Both regimes were well
      tolerated. Patients in the busulfan plus vitamin A arm had somewhat longer
      durations of clinical progression-free survival (median 46 months) and overall
      survival (51 months) compared to those in the busulfan arm (medians 38 and 44
      months). However, the differences were not statistically significant (one-tailed
      P = 0.11 for clinical progression-free survival, 0.081 for survival). After
      adjustment for significant factors identified in an additional exploratory
      multivariate analysis, risk of clinical progression or death was 53% (P = 0.022)
      greater and risk of death 60% (P = 0.014) greater among busulfan patients. Given
      the relatively large though non-significant difference between treatment arms,
      the limited statistical power of the study, and the likelihood that oral vitamin
      A may not be the most effective means of delivering retinoid therapy, we conclude
      that further investigation of retinoids in chronic phase CML is warranted.

PMID- 7564471
TI  - A novel intracellular antigen in HL-60 cells that changes in molecular weight
      after granulocytic and monocytic differentiation.
AB  - The present study reports the identification and partial characterization of a
      novel antigen with M(r) 100,000 by a monoclonal antibody (D29A8) that was
      obtained by immunizing BALB/c mice with nuclei of HL-60 cells. D29A8 detected
      mainly a nucleolar macromolecule with M(r) 100,000 (p100). On the other hand,
      when HL-60 cells were induced to differentiate either into a granulocytic or
      monocytic pathway, the antibody detected mainly a cytoplasmic macromolecule with
      M(r) 95,000 (p95). Since two subtypes of the antigen (p100 and p95) appear to be
      present in the same cells that differ in the stage of cell differentiation, the
      antigen may play an important role in cellular differentiation.

PMID- 7564472
TI  - Characterization of a HTLV-I-infected cell line derived from a patient with adult
      T-cell leukemia with stable co-expression of CD4 and CD8.
AB  - A long-term T-cell line, termed SP+, was developed from a human T-cell leukemia
      virus type I (HTLV-I)-infected patient with adult T-cell leukemia that is
      dependent on exogenous IL-2 for growth. The SP+ expresses a full complimentation
      of HTLV-I-specific viral proteins, and contains replication competent viral
      particles. Restriction enzyme digestion followed by Southern blot analysis
      demonstrated the presence of a single integrated proviral copy and limiting
      dilution analysis confirmed the clonality of the cell line. Interestingly,
      phenotypically, the SP+ cell line is CD2+, CD3+ and coexpresses CD4 and CD8, yet
      lacks TCR alpha beta and TCR tau delta expression. Further ontogenetic
      characterization of the SP+ cell line demonstrated the lack of thymic T-cell
      precursor markers, including absence of cell surface expression of CD1,
      intracellular thymic terminal deoxynucleotidyl transferase (TdT) enzyme, as well
      as message expression for V(D)J recombinase activating gene-1 (RAG-1).
      Furthermore, the SP+ cell did express the message for the CD3 delta chain. Taken
      together, these data suggest that the SP+ cell line resulted from HTLV-I
      infection of a mature CD4+/CDB+ lymphocyte. This cell line can be potentially
      useful as a model, both for regulation of cellular functions by HTLV-I and for
      immunologic functions of mature dual CD4/CD8 positive T-cells.

PMID- 7564473
TI  - Megakaryocytes and fibroblasts--interactions as determined in normal human bone
      marrow specimens.
AB  - An in vitro study was performed to investigate possible interactions between
      megakaryocytes and bone marrow fibroblasts, both obtained from healthy donors. We
      were able to demonstrate that the proliferation of fibroblasts increased
      significantly by co-culturing these cells with megakaryocytes for 6 days.
      Addition of neutralizing antibodies for PDGF and TGF beta 1, caused a significant
      reduction of fibroblast growth. Inhibition of cell to cell contacts via tissue
      culture inserts generated a conspicuous impairment of fibroblast proliferation
      compared with megakaryocyte-fibroblast co-cultures, where contact was allowed.
      Hence, our findings suggest that a close spatial relationship between
      megakaryocytes and fibroblasts is needed for the activation of growth in normal
      human bone marrow. Neighbouring of megakaryocytes and fibroblasts seems to be
      necessary in order to achieve a certain threshold of local growth factor
      concentration. Our results are in keeping with the assumption that PDGF and TGF
      beta 1, are secreted by normal human megakaryocytes in very low concentrations
      and promote significantly fibroblast proliferation.

PMID- 7564474
TI  - Spontaneous cytokine overproduction by peripheral blood mononuclear cells from
      patients with myelodysplastic syndromes and aplastic anemia.
AB  - We studied spontaneous cytokine production by peripheral blood mononuclear cells
      (PBMC) obtained from 14 patients with aplastic anemia (AA) and 28 various
      myelodysplastic syndromes (MDS). The levels of interleukin-6, interleukin-1 beta,
      and tumor necrosis factor-alpha in cultured PBMC were measured by ELISA. The
      average levels of these cytokines were higher in AA or in refractory anemia (RA)
      than in RA with excess of blasts (RAEB) or in RAEB in transformation (RAEB-T).
      Marked cytokine overproduction was observed in RA as well as in AA. High cytokine
      levels were observed in hypocellularity and low blast cell counts in the bone
      marrow. These results may suggest that the increase of cytokines may be a
      reactive response in hypocellular bone marrow.

PMID- 7564475
TI  - Augmentation by aphidicolin of 1-beta-D-arabinofuranosylcytosine-induced c-jun
      and NF-kappa B activation in a human myeloid leukemia cell line: correlation with
      apoptosis.
AB  - 1-beta-D-arabinofuranosylcytosine (ara-C) (2 microM) can induce apoptosis in a
      human myeloid leukemia cell line, U937, after 4 h of incubation. Pretreatment of
      cells with aphidicolin (2 microM) augments ara-C-induced apoptosis, since it was
      first observed at 0.4 microM ara-C and became more intense at 2 and 10 microM.
      Although aphidicolin itself had a marginal effect on c-jun expression, it
      significantly augmented ara-C induced c-jun upregulation by shortening the lag
      time and lowering ara-C concentrations necessary for the induction of detectable
      c-jun transcripts. Aphidicolin and ara-C acted synergistically to increase NF
      kappa B DNA binding activity as determined by an electrophoretic mobility shift
      assay. Expression of c-myc was slightly increased through the DNA degradative
      phase, and was then downregulated. Thus, the activation of NF-kappa B and c-jun
      expression seems to be well correlated with the potentiation by aphidicolin of
      ara-C-induced apoptosis.

PMID- 7564477
TI  - Aminopeptidase-N (CD13; gp 150): contrasting patterns of enzymatic activity in
      blood from patients with myeloid or lymphoid leukemia.
AB  - We have investigated the compartmentalization of aminopeptidase-N-like activity
      in various blood fractions obtained from patients with acute lymphoid (ALL) or
      myeloid (AML) leukemia. The primary difference appears not to be the absolute
      level of overall activity, but rather the relative proportions of the different
      forms of activity detected. Thus, despite similar levels of total aminopeptidase
      N-like activity detected in cells from different leukemic groups, true
      aminopeptidase-N/CD13 activity was only detected in cells derived from AML
      patients. Even in these patients, however, most of the detected aminopeptidase-N
      like activity ( > 80%) could not be attributed to aminopeptidase-N/CD13. In
      marked contrast, plasma from leukemic patients also contained substantial total
      aminopeptidase-N-like activity, of which (irrespective of leukemic group) most
      could be attributed to aminopeptidase-N/CD13. Whilst slightly higher levels of
      total activity were obtained in plasma from AML patients compared to ALL
      patients, there was no difference in the relative proportion attributable to
      aminopeptidase-N/CD13 (approximately 80% of total aminopeptidase-N-like
      activity). Evaluation of total aminopeptidase-N-like activity present in whole
      blood gave differential patterns, and whilst only a proportion (20-40% of total
      aminopeptidase-N-like activity) could be attributed to true aminopeptidase
      N/CD13, blood from patients with CD13+ AML showed the greatest activity so
      attributable. In total, our results outline the complexities of peptidase
      activities present within blood of leukemic individuals, and may, in part,
      explain the variability of previous studies attempting to associate prognostic
      features with phenotypic expression of CD13.

PMID- 7564476
TI  - Effects of bryostatin-5 and hematopoietic growth factors on acute myeloid
      leukemia cell differentiation, proliferation, and primary plating efficiency.
AB  - We examined the effect of bryostatin-5 (bryo-5) with and without a combination of
      myeloid growth promoting factors on human acute myeloid leukemia (AML) cell
      growth, maturation, and primary plating efficiency. In vitro treatment of AML
      samples with bryo-5 induced a macrophage-like cell differentiation as evidenced
      by morphological changes, esterase staining, and cell surface expression of CD11a
      and CD18. AML cells exposed to growth factors doubled their cell numbers
      following culture, this increase being abrogated by co-exposure to bryo-5. An
      antiproliferative effect, as well as the antagonistic interaction of bryo-5 with
      growth factors, was confirmed in methylcellulose clonogenic assays. Together,
      these findings indicate that the compound bryo-5 exerts an anti-proliferative
      effect on AML cells and counteracts growth factor induced leukemic proliferation.

PMID- 7564478
TI  - Bryostatin 1 induces apoptosis and augments inhibitory effects of vincristine in
      human diffuse large cell lymphoma.
AB  - Bryostatin 1 (Bryo1), a macrocyclic lactone and a protein kinase C activator, is
      isolated from the marine bryozoan Bugula neritina. In this study we describe its
      effect, alone or after sequential use with vincristine (VCR), on the human
      diffuse large cell lymphoma cell line WSU-DLCL2. Our results show that both Bryo1
      and VCR induced apoptosis as demonstrated by morphological examination, DNA flow
      cytometry (FCM), and DNA fragmentation on agarose gel electrophoresis. Cells
      pretreated for 24 h with Bryo1 and then exposed to VCR showed an increase in
      apoptosis compared to cells that were exposed to Bryo1 or VCR alone. We also
      studied the effects of Bryo1, VCR and their combination on cell growth, bcl-2 and
      p53 expression, and inhibition of cell proliferation as measured by [3H]
      thymidine incorporation. Cell analysis showed significant growth inhibition of
      WSU-DLCL2 cells by the Bryo1/VCR combination as compared to either agent alone.
      Immunocytochemistry (ICC) revealed that relative bcl-2 oncoprotein expression was
      decreased in cells treated with Bryo1, or VCR separately and was abolished by
      combining both drugs. When examined by ICC, WSU-DLCL2 cells were initially
      negative for the p53 protein. However, upon treatment with the above agents, the
      relative expression of p53 was moderate on Bryo1-or VCR-treated cells and strong
      on cells treated with the Bryo1/VCR combination. Cell proliferation as measured
      by [3H]-thymidine incorporation revealed significant inhibition of tumor growth
      by exposure to the agents when compared to the control. In contrast, Bryo1, VCR
      and their combination did not show any inhibition of normal bone marrow growth.
      These findings taken together, suggest that the exposure of WSU-DLCL2 cells to
      Bryo1 prior to treatment with VCR enhances apoptosis, a phenomenon which might be
      exploited for future therapies.

PMID- 7564479
TI  - Translocation (8;21)(q22;q22) and the myelodysplastic syndrome.

PMID- 7564480
TI  - Effects of thromboxane A2 analogue on vascular resistance distribution and
      permeability in isolated blood-perfused dog lungs.
AB  - This study was designed to determine the effects of thromboxane A2 (TxA2) on the
      distribution of vascular resistance, lung weight, and microvascular permeability
      in isolated dog lungs perfused at a constant pressure with autologous blood. The
      stable TxA2 analogue (STA2; 30 micrograms, n = 5) caused an increase in pulmonary
      capillary pressure (Pc) assessed as double-occlusion pressure to 14.0 +/- 0.4
      mmHg from the baseline of 7.9 +/- 0.3 mmHg with progressive lung weight gain.
      Pulmonary vascular resistance increased threefold exclusively due to pulmonary
      venoconstriction. Pulmonary venoconstriction was confirmed in lungs perfused in a
      reverse direction from the pulmonary vein to the artery (n = 5), as evidenced by
      marked precapillary vasoconstriction and a sustained lung weight loss.
      Furthermore, in lungs perfused at a constant blood flow (n = 5), STA2 also caused
      selective pulmonary venoconstriction. Vascular permeability measured by the
      capillary filtration coefficient and the isogravimetric Pc at 30 and 60 min after
      STA2 infusion did not change significantly from baseline in any lungs studied.
      Moreover, elevation of Pc by raising the venous reservoir of the intact lobes (n
      = 5) to the same level as the STA2 lungs caused a greater or similar weight gain
      compared with the STA2 lungs. Thus, we conclude that TxA2 constricts selectively
      the pulmonary vein resulting in an increase in Pc and lung weight gain without
      significant changes in vascular permeability in isolated blood-perfused dog
      lungs.

PMID- 7564481
TI  - Short term effect of methotrexate in severe steroid-dependent asthma.
AB  - The steroid-sparing capacity of methotrexate in asthmatics is still being
      debated. The present study was undertaken to evaluate the effect of low-dose
      methotrexate on steroid consumption in patients with severe asthma, who require
      very high doses of systemic corticosteroids. We conducted a randomized, double
      blind, parallel clinical trial in 24 patients with long-standing asthma. After a
      3-week run-in period, patients received a 16-week course of either 15 mg of oral
      methotrexate weekly or matched placebo in addition to their previous asthma
      therapy. The daily steroid dose (at run-in 30 +/- 14 mg/day in the methotrexate
      group; 25 +/- 9 mg/day in the placebo group (NS)) decreased by 24% in the
      methotrexate group (p < 0.01) and by 5% in the placebo group (NS) during weeks 9
      16 of the treatment period when compared with run-in values. However, there was
      no difference in steroid consumption between the two groups at any time. We
      conclude that in patients with severe asthma who require very high doses of
      systemic corticosteroids, short-term treatment with methotrexate allows only a
      marginal steroid reduction. Our study does not support the use of methotrexate as
      a steroid-sparing agent in asthmatics.

PMID- 7564482
TI  - Lymphocyte subsets in bronchoalveolar lavage after exposure to Actinobacillus
      pleuropneumoniae in pigs previously immunized orally or by aerosol.
AB  - Young pigs were immunized with the lung-pathogenic bacterium Actinobacillus
      (Haemophilus) pleuropneumoniae by aerosol or orally using viable and inactivated
      bacteria. The cellular changes in the bronchoalveolar lavage (BAL) were studied
      in repeated lavages after the pigs were infected with live bacteria. The
      nucleated cells in the BAL were differentiated and lymphocyte subsets determined.
      There were no major differences between the two routes of immunization or between
      viable and inactivated bacteria. The immunization induced an increase in all
      lymphocyte subsets studied and in the appearance of plasma cells and lymphoid
      blasts. The infection did not cause a further increase except in granulocytes.
      The lack of a booster-type increase in lymphocytes in the BAL might indicate a
      different immunologic reaction of the lung or that lymphocytes of the BAL do not
      represent lung lymphocytes in general. The protective effect of the immunization
      might be deduced from the increase in lymphocytes after immunization but not from
      the reaction pattern after infection.

PMID- 7564483
TI  - The influence of pH on surface properties of lung surfactants.
AB  - Protein-lipid interactions at air-liquid interfaces are dependent on
      electrostatic charges, cations, anions, distribution of protons, and surface
      potential, which are influenced by pH changes. All of these factors may affect
      lung surfactant function. To verify the pH dependence of surface activity of
      pulmonary surfactant, we studied the in vitro effects of pH and Ca2+ on the
      surface tension-lowering abilities of various surfactants in an oscillating
      bubble surfactometer. Surface tension measurements were made of mixtures at known
      pHs or after the replacement of the subphase fluid of surfactant films with
      buffered saline at various pH values. At the pH range 4.0-7.0, the average
      equilibrium surface tension (EST)/minimum surface tension (MST) for natural
      surfactants human amniotic fluid and natural lung surfactant from rabbit lung
      lavage was 24/2 mN/m. At the same pH range, Exosurf and phospholipids alone had
      an EST/MST of 44/25 and 44/12 mN/m, respectively. Survanta (SUR) containing SP-B
      and SP-C and a phospholipid surfactant (KL4) containing a leucine/lysine peptide
      had an EST/MST of 29/5 and 36/3, respectively. Alkalinization of the subphase (pH
      > 7.4) significantly decreased the surface tension-lowering ability of SUR (P <
      0.01) and to a lesser extent that of KL4 surfactant (P < 0.05), but natural lung
      surfactants were not significantly affected over a pH range of 3-7.5. These data
      demonstrate that natural surfactants maintain their optimal surface activities
      over a broader pH range than do the commercial products because of a lack of SP
      A. Careful monitoring of the pH for optimal surface activity is recommended when
      evaluating surfactant function and the effects of specific inhibitors on this
      function.

PMID- 7564484
TI  - Lipid peroxidation in lung of rat stressed by immobilization: effects of vitamin
      E supplementation.
AB  - This study was carried out to examine the possibility of initiation of lipid
      peroxidation in the lung of Wistar albino male rats stressed by immobilization.
      The effects of vitamin E supplementation were also investigated. We found that
      immobilization of rats with normal pulmonary content of vitamin E caused lipid
      peroxidation in the lung. Decrease of the lung content of unsaturated fatty acids
      and vitamin E was also established. The immobilization-induced changes of all of
      these parameters were significantly inhibited by vitamin E injection (100 mg/kg
      body weight) for 7 days. A possible sequence of events leading to the initiation
      of lipid peroxidation and lung cell membrane damage in rats stressed by
      immobilization is discussed.

PMID- 7564485
TI  - Endobronchial radiation therapy for obstructing malignancies: ten years'
      experience with iridium-192 high-dose radiation brachytherapy afterloading
      technique in 365 patients.
AB  - From 1983 to 1993, 365 patients with obstructing endobronchial malignancies were
      treated by endobronchial high-dose radiation (HDR) iridium-192 afterloading. In
      346 patients, the objective was palliation, and in 19, the objective was
      curative. A dose of 5 Gy at 10 mm from the source axis was administered on three
      (palliation) and four (cure) occasions, at intervals of 14 days. The majority of
      patients were treated after exhaustion of external beam radiation therapy (EBRT),
      often in conjunction with other interventional bronchologic modalities such as
      endobronchial laser resection. Of the patients, 65% had a squamous cell
      carcinoma. Endobronchial HDR brachytherapy results in few acute complications and
      can be performed with no major discomfort on an outpatient basis. In
      approximately 66% of patients, a palliative effect is achieved, even after the
      exhaustion of conventional treatment. Life may be prolonged for a few months, but
      the enhancement of survival is difficult to assess for several reasons. Mean
      survival is 9 months for limited disease and 5 months for extensive disease.
      Endobronchial HDR brachytherapy influences the pattern of failure: a 21% rate of
      fatal hemorrhages is probably the result of the selection of patients for this
      treatment rather than a treatment-related complication. There is sufficient
      evidence to suggest the rational use of HDR brachytherapy in combination with
      EBRT to effect a cure, or even on its own when tumor growth is strictly limited.
      However, the standardization of radiotherapy and endoscopic indications is an
      urgent priority. Prospective, controlled, and cooperative studies are mandatory.
      Endobronchial iridium-192 HDR brachytherapy complements endobronchial laser
      resection and is currently an established technique in the treatment of advanced
      malignant airway obstruction.

PMID- 7564486
TI  - Heterogeneous activity of pulmonary vagal receptors during high-frequency
      oscillation ventilation.
AB  - The purpose of the study was to examine the response of vagal pulmonary slowly
      adapting stretch receptors (SAR) to high-frequency oscillation ventilation (HFO)
      in rabbits by analyzing the afferent activity recorded in vagal single-fiber
      preparations. The vagal afferent activity was recorded during short runs of HFO
      with a stroke volume of 2-3 ml/kg applied at oscillation frequencies (fosc) of 5,
      10, 15, 20, and 25 Hz and each frequency at three levels of mean airway pressure
      (P(aw)), namely, 1, 3, and 8 cm H2O. The receptor discharge rates during HFO were
      compared with those during quiet spontaneous breathing as well as during static
      lung inflations and deflations. The majority of SAR was stimulated by HFO,
      however, the SAR discharge patterns during HFO were less homogeneous than during
      static lung inflations. The heterogeneity of SAR responses to HFO became
      pronounced with increasing P(aw) and fosc. From the results, we conclude that HFO
      elicits heterogeneous discharge patterns of SAR, but the previously reported
      heterogeneity of responses of rapidly adapting receptors was even greater. This
      heterogeneity of vagal activity is probably the result of heterogeneous
      mechanical conditions within the lungs during HFO and may, in turn, give rise to
      the various types of respiratory reflex responses to HFO.

PMID- 7564487
TI  - Effects of corticosteroid inhalation therapy on the deposition pattern of Tc-99m
      human serum albumin radioaerosols in asthma.
AB  - This study evaluated the effects of steroid inhalation on the deposition pattern
      of Tc-99m human serum albumin (Tc-99m HSA) radioaerosols in 25 asthma patients. A
      total of 12 normal controls also underwent the same examination. The pattern of
      radioaerosol deposition was quantitatively evaluated as the percentage of total
      deposition (PTD) in the central, intermediate, and peripheral regions of the
      right lung. The baseline PTD was calculated before and after the administration
      of a 1-week course of inhalation therapy of 0.05 mg beclomethasone dipropionate
      four times daily. There were significant differences in PTD between normal
      controls and asthma patients. Significant differences were also found before and
      after corticosteroid inhalation therapy in asthma patients. In conclusion, a week
      long course of beclomethasone dipropionate inhalation therapy does influence the
      deposition patterns of aerosols in asthma patients, based on the findings of Tc
      99m HSA radioaerosol inhalation lung scintigraphy.

PMID- 7564491
TI  - Improving the scientific image of lymphology.

PMID- 7564492
TI  - Limb circumference measurement for recording edema volume in patients with
      filarial lymphedema.
AB  - To evaluate the impact of therapy and monitor the progression of filarial
      lymphedema, it is necessary to measure accurately the changes in limb edema
      volume. In this communication, we report the reliability of circumference
      measurements for recording volume changes. The measurements included the distal
      parts of limbs important for filarial lymphedema. In a series of 100 patients
      with unilateral lower limb lymphedema, both water displacement and circumference
      measurements were done. The results showed a significant correlation (r = 0.91; P
      = 0.0000) between the actual volume and that estimated by circumference
      measurement. Not only could volume of edema be calculated by circumference
      measurements, but the simple measurement of average circumference difference
      between the affected and normal limb accurately reflected the volume of actual
      edema.

PMID- 7564489
TI  - Tannin inhibition of protein kinase C in airway epithelium.
AB  - Tannin, a polydisperse polyphenol extracted from cotton bracts (CBE), has been
      implicated in the pathogenesis of byssinosis, a lung disease of mill workers. CBE
      tannin inhibits chloride secretion in airway epithelial cells by means of an
      unknown mechanism(s). Activation of protein kinase C (PKC) by PMA (phorbol 12
      myristate 13-acetate) in airway cells increases chloride secretion. The effect of
      tannin on this PKC pathway was examined, using canine tracheal epithelium mounted
      in Ussing chambers. PMA addition (10 nM) to the mucosal bath resulted in a 0.36
      +/- 0.07 microEq/cm2.h (mean +/- SEM, n = 20) increase in short-circuit current
      (Isc) and a 0.38 +/- 0.17 microEq/cm2.h increase in net chloride secretion
      (Jnet). The inactive 4 alpha-phorbol had no effect. Tannin addition to the
      mucosal bath produced a dose-dependent decrease in Isc and Jnet. In tissues
      pretreated with 2-50 micrograms/ml tannin, and subsequently stimulated with PMA,
      tannin inhibited PMA stimulation of chloride secretion beginning at a tannin
      concentration of 10 micrograms/ml (0.09 +/- 0.05 microEq/cm2.h [n = 10] increase
      in Isc and 0.08 +/- 0.03 microEq/cm2.h increase in Jnet with PMA after tannin
      pretreatment). At 50 micrograms/ml tannin, the stimulatory effect of PMA was
      completely abolished. The known PKC inhibitor, H-7 (20 microM), inhibited PMA
      stimulation, while chelerythrine (2 microM) had not effect on PMA-stimulated Isc
      and Jnet, and calphostin C was toxic to the airway epithelium. In membrane
      fragments, 2.5 micrograms/ml tannin inhibited the rate of histone III
      phosphorylation by PMA from 32.1 +/- 4.4 nmol/mg protein per min to 20.1 +/- 2.7
      nmol/mg protein per min (n = 7). In bovine airway cells, tannin pretreatment (2.5
      micrograms/ml) decreased the cytosolic activity of PKC but had no effect on PKC
      translocation to the membrane. We conclude that tannin inhibits chloride
      secretion in airway epithelial cells in part by inhibiting PKC.

PMID- 7564488
TI  - Pulmonary function survey in spinal cord injury: influences of smoking and level
      and completeness of injury.
AB  - Spirometry was performed on 165 subjects with spinal cord injury (84 with
      quadriplegia and 81 with paraplegia). Subjects were characterized by level of
      lesion as: high quadriplegia (HQ, C4 and above not requiring mechanical
      ventilation), low quadriplegia (LQ, C5-8), high paraplegia (HP, T1-7), and low
      paraplegia (LP, T8-L3). Thirty-nine subjects had complete motor lesions, and 126
      had incomplete motor lesions. Nonsmokers (54 with quadriplegia and 53 with
      paraplegia) were defined as those who had never smoked or those who had stopped
      smoking for 1 year. Current smokers (28 with quadriplegia and 28 with paraplegia)
      were defined as those who currently smoked cigarettes, cigars, and/or pipe or
      those who had quit for < or = 1 year. We found by linear regression analysis that
      forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak
      expiratory flow (PEF), and maximal voluntary ventilation (MVV) were inversely
      correlated with the level of injury (i.e., the higher the level of injury, the
      lower the parameter). In the HQ group, those with complete injury had
      significantly lower pulmonary function parameters than those with incomplete
      lesions. In contrast, there were no significant differences in pulmonary function
      parameters between complete and incomplete lesions in subjects in the LQ, HP, and
      LP groups. In the LQ, HP, and LP groups, the FEV1 and PEF were significantly
      lower in smokers than in nonsmokers. Thus, this study demonstrates the effects of
      completeness of injury and smoking on pulmonary function in a large group of
      subjects with spinal cord injury.

PMID- 7564493
TI  - Chylothorax in the dog and cat: a review.
AB  - Chylothorax is a rare but complex disorder in domestic animals. Etiologies
      include neoplasia, fungal infections, heartworm infestation, cardiac disease,
      thrombosis of the cranial vena cava, and congenital anomaly of the thoracic duct.
      Most cases of chylothorax in dogs and cats are idiopathic. Positive contrast
      lymphangiography on dogs and cats with chylothorax consistently reveals extensive
      lymphangiectasia of mediastinal and pleural lymphatics. Reported treatment
      modalities for chylothorax in animals include removal of the etiologic agent,
      such as a mediastinal tumor, thoracic duct ligation, and implantation of active
      or passive drainage devices such as a pleuroperitoneal shunt. Thoracic duct
      ligation has been most successful in our experience, but continued study is
      needed since treatment failures are common.

PMID- 7564490
TI  - Acute and chronic treatment with glucocorticosteroids, modifying the beta 2
      adrenergic response of the guinea pig trachea.
AB  - The effect of beta 2-adrenoceptor agonists on airway smooth muscle relaxation may
      be subject to desensitization. It could be modified by glucocorticosteroid
      treatment. An increase in the beta 2 agonist response by glucocorticosteroids in
      vitro has been described. We studied the effects of acute and chronic treatment
      with dexamethasone on the relaxation response of tracheal smooth muscle to beta 2
      agonists, fenoterol and salbutamol. Fenoterol showed a greater force of
      relaxation than salbutamol, and both drugs induced desensitization. Acute
      treatment with dexamethasone reduced desensitization to both beta 2 agonists.
      Chronic treatment (120 micrograms/kg of dexamethasone for 7 days) reduced the
      desensitization to fenoterol alone. Dexamethasone (200 micrograms/kg for 7 days)
      increased relaxation to salbutamol and reduced desensitization to both drugs. The
      interaction between beta 2 agonists and glucocorticosteroids could be important
      in the clinical use of both drugs in the treatment of asthma.

PMID- 7564494
TI  - Pregnancies after endolymphatic therapy of residual retroperitoneal Hodgkin
      lymphoma.
AB  - Three young women with Hodgkin lymphoma (stage III and IV) had residual
      retroperitoneal lymphoma after 6 cycles of standard chemotherapy. To preserve
      fertility, chemotherapy was subsequently continued as a single endolymphatic
      injection of 60 mg Bleomycin in oily suspension (Oil Bleo). Except for slight,
      transient fever in one patient, no side effects occurred. Follow-up plain X-rays
      with lipoidal stained lymph nodes showed a marked reduction in size of the
      retroperitoneal lymphomatous lymph nodes in all 3 patients. Each woman became
      pregnant between 2 and 14 months after endolymphatic therapy and bore healthy
      infants. Two of the women remain free of disease. The third has had a recurrence
      in the neck and has been treated with second-line intravenous chemotherapy.
      Endolymphatic therapy of retroperitoneal lymphoma may achieve a satisfactory
      result in selected patients while preserving fertility.

PMID- 7564496
TI  - Radiographic demonstration of intercostal lymphatics and lymph nodes.
AB  - The anatomy of the posterior intercostal lymphatics and lymph nodes is reviewed.
      These lymph nodes are occasionally visualized by bipedal conventional
      lymphography. Opacified and/or enlarged posterior intercostal lymph nodes may
      also be identified with computed tomography of the chest. Familiarity with the
      lymphatic drainage patterns of the intercostal spaces and recognition of abnormal
      intercostal lymph nodes may provide additional information regarding disease
      status in patients with inflammatory or malignant disease of the thorax.

PMID- 7564495
TI  - Assessment of truncal edema following breast cancer treatment using modified
      Harpenden skinfold calipers.
AB  - After initial treatment for breast cancer, lymphedema often affects the trunk as
      well as the arm. Evaluation of truncal swelling by the clinical "pinch test" of
      the posterior axillary fold is unreliable. Our aim was to develop an objective
      measurement, using modified Harpenden skinfold calipers. Standard Harpenden
      skinfold calipers exert a pressure of 12.6 g.mm-2, which rapidly squeezes edema
      fluid out of the skinfold. Springs were substituted to exert a lighter but
      relatively constant load (3.7 g.mm-2). Repeated skinfold thickness measurements
      on the same, normal subject then gave a relative standard deviation (r.s.d.) or
      coefficient of variation of 5%. The posterior axillary folds of 14 patients (age
      56 +/- 13 (s.d.) years) with an average 30% arm swelling were measured using the
      same procedure. Readings were taken at 10 s, and again after 60 s of sustained
      application to assess the rate of creep, or deformation with time, attributed to
      displacement of pressurized interstitial fluid. Two patients had clinically
      observable axillary fold swelling. Eight patients, including the above two,
      showed axillary fold swelling by caliper measurement, defined as a 10% increase
      over the contralateral side (2 r.s.d.'s). Creep was greater on the affected side
      in all 14 patients. Thus, modified calipers can detect axillary fold edema, and
      thereby provide an objective method for assessing changes in swelling after
      lymphedema treatment.

PMID- 7564498
TI  - A non-random chromosome abnormality found in precursor-B lineage acute
      lymphoblastic leukaemia: dic(9;20)(p1?3;q11).
AB  - A comparison of cytogenetical data on acute lymphoblastic leukaemia studied at
      four large European centres has revealed a non-random dicentric chromosome
      abnormality: dic(9;20) (p1?3;q11) in 10 patients, nine of whom were children. All
      had early precursor-B lineage ALL, and eight children had a non-standard risk
      clinical presentation. The origin of the dicentric chromosome was demonstrated
      using a range of chromosome banding techniques. This was confirmed by FISH using
      paints and centromeric probes for chromosomes 9 and 20, together with a number of
      cosmid probes. The follow-up time of these patients is presently too short and
      the number of patients too few to determine the prognostic significant of this
      chromosome abnormality.

PMID- 7564500
TI  - A new myeloproliferative disorder associated with chromosomal translocations
      involving 8p11: a review.
AB  - Chromosomal breakpoints associated with malignancy are known to cluster at
      particular regions of the karyotype. Based on a review of the literature we have
      identified a novel leukaemia syndrome associated with translocations involving
      8p11. This syndrome is distinct from the previously described translocation
      t(8;16)(p11;p13) associated with acute monoblastic leukaemia. We have summarized
      the clinical and cytogenetic features of 13 case reports which describe a
      myeloproliferative syndrome with eosinophilia, lymphadenopathy and a high
      incidence of T cell non-Hodgkin's lymphoma with progression to acute myeloid
      leukaemia. The translocations involving 8p11 were: either t(8;13)(p11-12;q11-12),
      t(8;9) (p11;q32-34) or t(6;8)(q27;p12). In two cases of t(8;13) molecular studies
      have mapped the chromosome 13 breakpoint to a 1.5 Mbp region, but a full
      molecular characterization of these translocations is required. In view of the
      striking clinicopathological and karyotypic similarities between these cases we
      propose that they be considered a single nosological entity and termed '8p11
      myeloproliferative syndrome'.

PMID- 7564497
TI  - Differentiation of lymphatics from blood vessels in the broad ligament of the
      swine using S-100 protein immunohistochemical localization in the vascular
      endothelium.
AB  - We examined the immunohistochemical staining characteristics of S-100 protein in
      the vessels of the broad ligament of the swine uterus. The endothelial cells of
      arterial vessels, lymphatics and blood capillaries as well as nerve fiber bundles
      showed S-100 protein positivity. In contrast, the endothelial cells of veins did
      not react for the S-100 antiserum. Immunoreactivity for S-100 protein in the
      endothelial cells of lymphatics did not consistently demonstrate strong staining
      intensity. Accordingly, we filled lymphatics with colored gelatin before
      immunohistochemical staining to facilitate identification of lymphatics under
      light microscopy. Numerous arterioles and capillaries (of which the endothelial
      cells were immunopositive for S-100 protein) in the lymphatic walls, especially
      those in the paraovarian vascular plexus, support the existence of a
      microvascular arterio-arterial rete mirabile network.

PMID- 7564499
TI  - CD30 expression in normal and neoplastic lymphoid tissue: biological aspects and
      clinical implications.
AB  - CD30 expression is found on Hodgkin and Reed-Sternberg cells, anaplastic large
      cell lymphoma cells and on activated B or T lymphocytes. Recently CD30 was shown
      to be a transmembrane receptor that is significantly homologous to the tumor
      necrosis factor receptor (TNFR) family. Ligands for most members of this family,
      including CD30, have now been identified. This review summarizes the role of the
      different TNFR family members in lymphocyte proliferation and differentiation in
      an attempt to understand more clearly the role of CD30 expression in the
      pathogenesis and clinical behavior of non-Hodgkin's lymphomas. We state that CD30
      expression is of prognostic relevance in primary cutaneous and nodal T cell
      lymphomas in contrast to the absence of clinical relevance of CD30 expression in
      B cell lymphomas.

PMID- 7564504
TI  - Chronic myeloid leukemia, BCR/ABL transcript, response to alpha-interferon and
      survival. The Italian Cooperative Study Group on Chronic Myeloid Leukemia.
AB  - There is increasing evidence for a relationship between specific genomic
      alterations and the distinctive features of leukemia, including the course and
      the response to treatment. In Philadelphia (Ph) positive chronic myeloid leukemia
      (CML) the BCR/ABL fusion genes can be transcribed in at least two different mRNAs
      that can either include (a2b3) or exclude (a2b2) the exon 3 of the major
      breakpoint cluster region in chromosome 22. We identified by polymerase chain
      reaction the transcript type in 146 patients with Ph+ CML who were enrolled in a
      prospective study of treatment with alpha-interferon (alpha-IFN) for at least 1
      year, and were followed for 39 to 84 months (median 60 months). The transcript
      was a2b3 in 84 cases (57%) and a2b2 in 62 cases (43%). A trend in favor of a2b3
      cases was observed, as to the karyotypic response after 1 year of alpha-IFN
      treatment (39% in the a2b3 cases vs 24% in the a2b2 cases) and 5-year survival
      rate, that was 71% (95% CI 59-82) in a2b3 cases vs 57% (95% CI 41-73) in a2b2
      cases. However, these differences were not significant, and we conclude that the
      identification of the transcript type by current methodology does not predict for
      response to alpha-IFN and for prognosis. Further studies may be required to
      confirm that conclusion, or to detect a true smaller difference.

PMID- 7564503
TI  - Acute lymphoblastic leukemia in the elderly: results of two different treatment
      approaches in 49 patients during a 25-year period.
AB  - This paper reported on a series of 49 elderly patients over 60 years of age
      affected by acute lymphoblastic leukemia (ALL), observed at our institution from
      1969 to 1993. The biological characteristics considered, median WBC count, FAB
      classification, immunophenotype at onset of disease, were no different from those
      of our adult ALL series. Overall complete remission (CR) rate of these patients
      was 59%, 18% had resistant disease and 23% died during induction. Overall median
      survival was 9 months and overall median duration of CR was 7 months. All
      patients were divided according to treatment into two groups: group A (13
      patients) received an intensive treatment including vincristine (VCR), prednisone
      (PDN), daunorubicin (DNR) and L-asparaginase (L-Asp), while in group B (36
      patients) were included patients who received mild conventional induction with
      VCR and PDN. In group A, 77% of patients achieved CR and 23% died during
      induction. All patients were hospitalized during induction treatment. During
      follow-up, among 10 CRs, five (50%) died in CR because of hemorrhage (two),
      infections (two) and myocardial infarction (one); five (50%) relapsed. Median
      survival was 4 months and median duration of CR was 3.5 months. In group B, 53%
      of patients obtained CR, 25% had resistant disease and 22% died during induction.
      During induction, 44% of patients were hospitalized. During follow-up, among 19
      CRs, 14 (74%) relapsed and three (15%) died in CR because of infection (two) and
      cardiorespiratory failure (one). Three patients (15%) are still alive: two in
      first CR and one in second CR. No statistical differences between the two groups
      in terms of CR rate or survival were noted. Standardized therapeutic trials are
      needed better to evaluate results in these patients, considering also the
      introduction of new therapeutic agents or supportive treatments, such as growth
      factors.

PMID- 7564502
TI  - A phase II study of menogaril (7R-O-methylnogarol) in patients with
      relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative
      Oncology Group.
AB  - Fifty-one patients (47 evaluable) with AML, 27 in first relapse and 20 either in
      second relapse or refractory were treated with menogaril, 100 mg/m2/day as a 90
      min infusion daily for 5 days. The complete response (CR) rate was 17% (8/47),
      and there was one partial response. Seven of eight responders were in first
      relapse with a 26% response rate among first relapse patients (7/27). The median
      duration of survival was 3 months for all first relapse patients and 4.3 months
      for all other patients. Toxicity included grades 3-4 pancytopenia and fever (100%
      of patients) and grades 3-4 stomatitis and hepatic enzyme elevation (25% of
      patients). Grades 3-4 cardiac toxicity occurred in three patients (two grade 3
      arrhythmias and one heart block). All had previously received anthracyclines.
      Remission duration was 1.6-48+ months; two patients underwent bone marrow
      transplantation and continue in CR at 36+ and 48+ months. The nontransplanted
      patients remained in CR 1.6, 2.0, 3, 7, 14 and 27 months. Activity and toxicity
      of menogaril in this study were comparable to that of other clinically useful
      anthracyclines in AML. Further investigation of this agent in AML is warranted.

PMID- 7564501
TI  - Phase I trial of high-dose tamoxifen as a modulator of drug resistance in
      combination with daunorubicin in patients with relapsed or refractory acute
      leukemia.
AB  - Tamoxifen and its main metabolite N-desmethyltamoxifen (NDMTmx) have been shown
      to increase intracellular daunorubicin (DNR) levels in human leukemia cell lines
      that display the multidrug resistant (MDR) phenotype. We designed a phase I dose
      escalation study of Tmx (200-700 mg/day p.o. for 7 days) in combination with a
      fixed dose of DNR (50 mg/m2 intravenously on days 5, 6 and 7) in patients with
      advanced leukemia to determine whether this combination could be given safely and
      whether plasma levels of 10 microM, the effective in vitro MDR modulator
      concentration, could be achieved. Pharmacologic studies of Tmx, NDMTmx and DNR,
      and its main metabolite daunorubicin-ol (DNR-ol) were performed as was
      determination of P-glycoprotein (Pgp) using a monoclonal antibody that recognizes
      an external epitope of the molecule. A total of 14 patients (median age 50, range
      22-67) were treated at the following dose levels: 200 mg/day: three patients; 400
      mg/day: four patients; 550 mg/day: three patients; and 700 mg/day: four patients.
      Two patients with relapsed AML achieved remission. Toxicity of the combination
      was similar to that seen with DNR alone and no severe hepatic, cardiac or retinal
      toxicity was noted. Plasma Tmx levels approached 7 microM at the two highest dose
      levels studied; plasma levels of NDMTmx were slightly less. The area under the
      curve for DNR and its main metabolite daunorubicin-ol (DNR-ol) did not show
      significant changes with escalation of Tmx dose. This phase I study suggests that
      concentrations of Tmx high enough to reverse the MDR phenotype can be approached
      and that the combination of high-dose Tmx with a standard dose of DNR has an
      acceptable toxicity profile. More evaluation in phase II studies is necessary to
      define further its role as an MDR modulator.

PMID- 7564506
TI  - Expression of multidrug resistance-associated protein (MRP) and multidrug
      resistance (MDR1) genes in acute myeloid leukemia.
AB  - The frequency, prognostic value and interrelation of MRP and MDR1 gene
      expressions were investigated by quantitative reverse transcription polymerase
      chain reaction (RT-PCR) in 91 cases of de novo acute myeloid leukemia (AML), of
      which 51 were newly diagnosed, 21 were relapsed, and 19 were refractory patients.
      As compared with normal bone marrow cells and peripheral granulocytes, an
      overexpression of MRP gene was found in 24% (22 of 91) cases of de novo AML. The
      incidence of MRP gene overexpression tended to be higher in relapsed patients
      than in newly diagnosed patients (38 vs 18%, P = 0.063). In 52 evaluable newly
      diagnosed and relapsed patients treated with MDR-related drugs, both MRP and MDR1
      gene overexpressions correlated to a higher rate of emergence of clinical drug
      resistance (83 vs 22%, P = 0.005; and 67 vs 24%, P = 0.045, respectively). A
      positive correlation was found between MRP and MDR1 gene overexpressions (R =
      0.53, P < 0.001). Analysis of 46 evaluable MDR1-negative cases revealed a trend
      for higher resistant disease rate in MRP-positive patients as compared with MRP
      negative patients (100 vs 20%, P = 0.053). These data suggest that MRP, like
      MDR1, may have an important negative impact on the outcome of chemotherapy, and
      that there may be a common mechanism of induction for the overexpression of these
      two genes.

PMID- 7564505
TI  - Topoisomerase II alpha gene expression in childhood acute lymphoblastic leukemia.
AB  - Previously, we showed that in vitro resistance to daunorubicin (DNR) at initial
      diagnosis was related to a poor long-term clinical outcome in childhood acute
      lymphoblastic leukemia (ALL), and that cells of relapsed ALL were in vitro more
      resistant to DNR than cells of untreated ALL. Topoisomerase II (Topo II) is an
      intracellular target for anthracyclines and epipodophyllotoxins. Decreased levels
      and/or activity of Topo II have been associated with multidrug resistance in cell
      lines. We investigated Topo II alpha gene expression in fresh leukemic samples
      from 19 children with untreated and 14 children with relapsed ALL using a
      sensitive RNase protection assay. The in vitro cytotoxicity of the Topo II
      inhibitors DNA and teniposide (VM26) was measured using the MTT assay, and the
      cell cycle distribution of leukemic samples was analyzed by DNA flow cytometry.
      Results showed that (1) relapsed ALL samples were more resistant to DNR, but not
      to VM26 compared to untreated samples; (2) large interpatient variations existed
      in both Topo II alpha gene expression and in vitro cytotoxicity results; (3) Topo
      II alpha gene expression was detectable in 29/33 childhood ALL samples with a
      median expression of 5% the level of a relatively chemosensitive human small cell
      lung cancer cell line; (4) Topo II alpha gene expression did not differ between
      untreated and relapsed ALL; (5) Topo II alpha gene expression was positively
      correlated with the percentage of ALL cells in S- and G2M-phase, but not with the
      in vitro cytotoxicity of the drugs tested. In conclusion, resistance to DNR in
      childhood ALL can not be explained by decreased levels of Topo II alpha gene
      expression, but additional Topo II activity studies in fresh leukemia samples may
      need further exploration.

PMID- 7564507
TI  - Direct evidence for the participation of bcl-2 in the regulation by retinoic acid
      of the Ara-C sensitivity of leukemic stem cells.
AB  - All-trans retinoic acid (ATRA) increases the sensitivity of AML blast cells to
      cytosine arabinoside (Ara-C) or daunorubicin (DNR) when ATRA is given after drug.
      We have proposed that down-regulation of bcl-2 is part of the mechanism by which
      ATRA regulates drug sensitivity. To test this hypothesis cDNA encoding bcl-2 was
      transfected into cells of the continuous lines OCI/AML-2 and OCI/AML-5. Four
      transfectant lines were isolated; three contained transfected bcl-2 in the sense
      orientation (AML5-BCL2sa, AML5-BCL2sb and 2-bcl2) and one with anti-sense bcl
      2(AML5-bcl2as). The presence of the transfected gene was demonstrated by Northern
      blot; translation of the sense transfected genes into protein was demonstrated by
      Western blotting. Lines with sense-oriented transfected bcl-2 were significantly
      less sensitive to Ara-C or H2O2 than the parental lines; the cells with anti
      sense transfected genes were more sensitive than their parent but the difference
      did not reach statistical significance. The effect of ATRA on bcl-2 expression
      was compared in sense-transfected cells and their parents; by Northern blotting
      it was shown that the endogenous but not the transfected genes were down
      regulated after ATRA exposure. The capacity of cells with transfected genes to
      respond to ATRA was tested by obtaining Ara-C survival curves for ATRA-treated
      cells. Compared to controls not exposed to ATRA, the transfected cells showed
      little or statistically insignificant changes in Ara-C sensitivity after ATRA
      treatment. We conclude that data from the transfectants provides evidence that
      expression of bcl-2 is a determinant of sensitivity to Ara-C and H2O2; and that
      the effect of ATRA on sensitivity requires the presence of bcl-2 genes in
      association with regulatory elements.

PMID- 7564509
TI  - L-asparaginase may potentiate the leukemogenic effect of the epipodophyllotoxins.
AB  - The risk for induction of epipodophyllotoxin-related acute myeloid leukemia (AML)
      depends largely on the schedule of drug administration and, to a lesser degree,
      the cumulative dose. Concomitant use of other genotoxic drugs, such as alkylating
      agents and cisplatin, can increase the hazard further. We have treated 154
      consecutive higher-risk cases of acute lymphoblastic leukemia in our recent Total
      Therapy Study XIII with an intensive post-remission regimen of chemotherapy that
      included etoposide given every other week or less often-a schedule associated
      with a relatively low cumulative incidence of secondary AML in our Study XI.
      Unexpectedly, four patients have developed secondary AML at 12 to 23 months from
      the start of treatment (median, 16 months). The 2-year cumulative risk estimate
      significantly exceeds that for 185 historical controls in Study XI whose
      continuation regimen included epipodophyllotoxins every other week: 5.4% (95%
      confidence interval, 0-11%) compared with 1.1% (0-2.6%), P = 0.046. Compared to
      patients treated in Study XI, those enrolled in Study XIII receive fewer
      scheduled doses of epipodophyllotoxin (48 (all etoposide) vs 63 (30 etoposide, 33
      teniposide)) but 16 to 19 additional doses of L-asparaginase and eight additional
      doses of high-dose methotrexate, all within the week preceding etoposide
      treatment. We attribute the apparently increased rate of secondary AML in Study
      XIII to the use of L-asparaginase immediately before etoposide administration. On
      this schedule, the enzyme could increase systemic exposure to etoposide or its
      catechol metabolites and reduce the ability of cells to repair DNA damage.

PMID- 7564510
TI  - A new t(2;5) translocation in a null cell type CD30 positive anaplastic large
      cell lymphoma case.
AB  - Anaplastic large cell lymphoma (ALCL) expressing the CD30 antigen is an uncommon
      subtype of non-Hodgkin's lymphoma characterized by distinct morphological and
      clinical features. The recurrent chromosomal abnormality found in these tumours
      is a t(2;5)(p23;q35) which has been detected in a minority of these cases,
      predominantly with a T cell immunophenotype. We report here a CD30 positive null
      cell type ALCL case cytogenetically characterized by a new type of t(2;5)
      translocation with distinct breakpoints at 2q37 and 5q31. FISH with a panel of 5q
      specific DNA probes applied in this case allowed for a mapping of a 5q31
      breakpoint region between the locus for IL-3 (proximally) and CI5-56 probe
      (distally). These results point to a localization of unknown gene(s) on the long
      arm of chromosome 5 that, in addition to the NPM gene at 5q35, may be involved in
      the pathogenesis of some CD30+ ALCL.

PMID- 7564508
TI  - Intracellular pharmacokinetics of 2-chlorodeoxyadenosine in leukemia cells from
      patients with chronic lymphocytic leukemia.
AB  - 2-Chlorodeoxyadenosine (2-CdA) is an important agent in the treatment of hairy
      cell leukemia and chronic lymphocytic leukemia (CLL). Others have reported that
      levels of 2-CdA phosphates present in human leukemia cells decline rapidly when
      the cells are in 2-CdA-free medium (Santana et al. J Clin Oncol 1991; 9: 416
      422). In the present study, time-courses of 2-CdA loss from CLL cells were
      biexponential: the mean half-life of the initial phase was 0.30 +/- 0.18 h; the
      presence of 0.5 microM nitrobenzylthioinosine (NBMPR, a classical inhibitor of
      nucleoside transport) in the suspending medium, significantly decreased the
      initial rate of 2-CdA efflux (mean half-life, 0.43 +/- 0.22 h). As a consequence,
      AUCs (areas under time-course plots) were significantly higher in the NBMPR
      treated cells (4.56 +/- 2.01 pmol.h/10(6) cells, n = 19) than in untreated
      control cells (3.83 +/- 1.74 pmol.h/10(6) cells; n = 19). 2-CdA was the principal
      efflux product released into the medium from 2-CdA-loaded CLL cells. We conclude
      that nucleoside transport processes contribute to the efflux of 2-CdA from CLL
      cells and that NBMPR may be useful as a retentive agent.

PMID- 7564511
TI  - A late-appearing Philadelphia chromosome in acute lymphoblastic leukemia
      confirmed by expression of BCR-ABL mRNA.
AB  - We report two cases of acute lymphoblastic leukemia (ALL) with a late-appearing
      Philadelphia chromosome (Ph1), confirmed by the expression of BCR-ABL mRNA, using
      the reverse transcriptase/polymerase chain reaction (RT/PCR) technique. The first
      patient was a 10-year-old boy with precursor B cell type ALL-L1 (FAB
      classification). At diagnosis, no metaphase cells were found by chromosome
      analysis and BCR-ABL mRNA was not observed. At the beginning of relapse, which
      occurred after 7 months of complete remission, a normal karyotype was observed.
      At the terminal stage, leukemic cells with Ph1 and BCR-ABL mRNA for the P190
      variety were observed. The second patient was a 12-year-old boy with immature T
      cell type ALL-L1. The metaphase cells showed a 9p- chromosome at diagnosis and
      Ph1 appeared in addition to 9p- at relapse. Hybrid mRNA for the P210 variety was
      detected only when Ph1 had developed. The blast cells with Ph1 were derived from
      the original leukemic clone through clonal evolution, since the same clonal
      rearrangements of IGH or TCRB were detected in leukemic cells obtained both at
      diagnosis and relapse in both patients. Thus, in both cases, Ph1 was detected
      only in the course of ALL along with expression of BCR-ABL mRNA. This observation
      also confirmed that, as in de novo Ph1-positive ALL, both the P190 and P210
      varieties of BCR-ABL mRNA are observed in ALL with late-appearing Ph1.

PMID- 7564512
TI  - Expression of c-myc oncoprotein in chronic T cell leukemias.
AB  - T cell clones in patients with ataxia telangiectasia (AT) and T cell
      prolymphocytic leukemia (T-PLL) have identical chromosome abnormalities, namely
      inv(14)(q11q32), t(14;14)(q11;q32) and t(X;14)(q27;q11). In T-PLL and AT
      developing T cell leukemia, the above abnormalities occur frequently together
      with trisomy for 8q. We postulated that the additional abnormalities of
      chromosome 8, where the c-myc oncogene is mapped to 8q24, may play a role in the
      development of overt leukemia. DNA analysis using the CD1A c-myc probe did not
      reveal rearrangements of the c-myc gene by Southern blotting. We have used a
      monoclonal antibody for the c-myc protein to investigate the level of expression
      in 11 patients with T-PLL and two with Sezary cell leukemia and compared it with
      levels seen in normal lymphocytes. Significantly higher levels were observed in
      patients compared with controls (P < 0.0001). The highest levels of c-myc were
      seen in eight cases with trisomy for 8q resulting from an i(8q). One patient was
      investigated before and after treatment. In the active state, c-myc showed a
      level of 64.36 units (range 20-200). After treatment a residual population of
      malignant cells showed a c-myc level of 155 (range 90-280). This study suggests
      that the increased expression of c-myc as a result of trisomy for 8q may have a
      role in the pathogenesis of de novo T-PLL and T cell leukemia supervening AT and
      that there may be a correlation between c-myc levels and resistance to therapy.

PMID- 7564513
TI  - Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing
      V alpha 1 or V alpha 14 elements.
AB  - Human acute lymphoblastic leukemia cell lines represent valuable tools to
      investigate distinct steps of the complex regulatory pathways underlying T cell
      receptor recombination and expression. A case in point are V delta 2D delta 3 and
      subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic
      pre-B cells as well as in normal lymphopoiesis. The functional expression of
      these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by
      alternative splicing events. In this report we show that alternative splicing at
      cryptic splice donor sites within V elements is not a unique feature of hybrid
      TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR,
      alternatively spliced products were observed in TCR alpha recombinations
      containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral
      blood cells and thymocytes, the leukemia cell line JM expressing functional V
      alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA
      species.

PMID- 7564514
TI  - Detection of the ageing-associated 5-Kb common deletion of mitochondrial DNA in
      blood and bone marrow of hematologically normal adults. Absence of the deletion
      in clonal bone marrow disorders.
AB  - In recent years, a variety of chronic degenerative diseases that mainly involve
      brain, heart and muscle have been shown to result from mutations in mitochondrial
      DNA (mtDNA). A 4977-bp deletion (mtDNA-4977, also known as the common deletion)
      is the most frequent abnormality in patients with mitochondrial myopathies. A low
      percentage of mtDNA-4977 is also found in various tissues of normal ageing
      individuals. Accumulation of this deletion as well as other mtDNA deletions and
      point mutations is thought to contribute to normal cell ageing. We examined blood
      and bone marrow samples of 63 hematologically normal patients undergoing
      sternotomy for cardiac surgery. Using short-cycle PCR, which favors the
      amplification of molecules carrying large deletions, we detected the common
      deletion in 22 (35%) of the patients. In one of the probands, a hitherto unknown
      4867-bp deletion was identified (nt 8561-13429). In each sample the percentage of
      mtDNA-4977 was very low, since detection always required primer-shift
      reamplification of a primary PCR product. Because mtDNA molecules with large
      deletions are known to be progressively enriched through their tendency to
      replicate more rapidly than full-size mtDNA, the small amount of mtDNA-4977
      detected is likely to be concentrated in a small fraction of cells. The common
      deletion was not detectable in 20 patients with myelodysplastic syndromes (MDS),
      20 patients with acute myeloid leukemia (AML), and 10 patients with chronic
      myeloid leukemia (CML). The seeming paradox of detectability of mtDNA-4977 in
      hematologically normal individuals and its absence in clonal myeloid disorders is
      explained by varying selection against self-renewing stem cells harboring the
      common deletion. Selection appears to be effective under circumstances of
      proliferative stress (eg among continuously proliferating stem cells in clonal
      hematopoiesis), whereas in normal steady-state hematopoiesis, affected stem cells
      persist because they are rarely recruited into cell cycle and can thus tolerate
      mitochondrial dysfunction.

PMID- 7564515
TI  - CDR3 size analysis of T cell receptor V beta transcripts: follow-up study in a
      patient with T cell acute lymphoblastic leukemia.
AB  - T cell acute lymphoblastic leukemia (T-ALL) is generally considered to be a
      clonal disorder arising as an expansion of committed lymphoid precursors. The
      generation of functional T cell receptor (TCR) genes involves DNA rearrangement
      processes. This predisposes immature lymphoid cells to abnormal rearrangements.
      Previous analysis of the TCR genes strongly suggested the clonal origin of human
      T-ALL. We present a sensitive clonal analysis of bone marrow TCR V beta
      transcripts in a case of T-ALL. This study allows the analysis not only of TCR V
      beta transcripts in tumor cells but also the temporal modification of the global
      TCR repertoire in the follow-up of clinical specimens from bone marrow aspirates.
      Moreover, we used clone-specific junctional region oligonucleotide probes
      corresponding to the clonal leukemic population for the molecular monitoring of
      the malignant clone throughout the clinical course of the disease. This molecular
      fingerprint appears to be a sensitive method to detect minimal residual disease.
      It shows that junctional regions of rearranged TCR beta genes corresponding to
      the tumor cells can also be detected at the time of the complete remission.

PMID- 7564516
TI  - Effect of 5637-conditioned medium and recombinant cytokines on P-glycoprotein
      expression in a human GM-CSF-dependent leukemic myeloid cell line.
AB  - This study was aimed at evaluating the influence of 5637-conditioned medium (5637
      CM) and human recombinant cytokines on both expression and function of P
      glycoprotein (P-gp) in TF-1, a GM-CSF/IL-3-dependent acute myeloid leukemia cell
      line which constitutively expresses functional P-gp. P-gp expression was measured
      by flow cytometry using MRK16 monoclonal antibody. P-gp function was measured by
      rhodamine 123 (Rh 123) efflux kinetics. When TF-1 cells were cultured with 5637
      CM (50% v/v), both P-gp expression and P-gp efflux capacity were increased in a
      time-dependent manner with a 4-fold increase in P-gp expression level at day 6
      whereas TF-1 cell differentiation status remained unchanged as assessed by
      morphological studies, phenotypical and cytochemistry analysis. Recombinant
      cytokines including GM-CSF, G-CSF, IL-1 beta, IL-6, stem cell factor, LIF,
      erythropoietin, and IL-3 had no effect on P-gp expression whereas TNF alpha
      induced dose- and time-dependent P-gp and mdr-1 gene overexpression. However, TNF
      alpha-induced P-gp overexpression had no influence on P-gp efflux capacity.
      Furthermore, when TF-1 cells were exposed to IL-3 for periods longer than 1
      month, we found that P-gp efflux capacity was increased as compared to cells
      cultured with GM-CSF whereas P-gp expression was unchanged. Both TNF alpha and IL
      3 did not induce TF-1 differentiation. Collectively, these results suggest that
      cytokines may influence both expression and function of P-gp in TF-1 cells
      without interfering with their differentiation status. In contrast to cytokines,
      phorbol esters enhanced expression and efflux capacity of P-gp in parallel with
      TF-1 cell monocytic differentiation. Finally, our study suggests that paracrine
      and/or autocrine secretion of cytokines may interfere with P-gp activity in some
      acute myeloid leukemia cells.

PMID- 7564517
TI  - Prolonged persistence of PCR-detectable minimal residual disease after diagnosis
      or first relapse predicts poor outcome in childhood B-precursor acute
      lymphoblastic leukemia.
AB  - The follow up of minimal residual disease (MRD) in childhood B-precursor ALL by
      polymerase chain reaction (PCR) may be of help for further stratification of
      treatment protocols, to improve outcome. However, the clinical relevance of this
      approach has yet to be defined. We report the retrospective follow-up of MRD in
      bone marrow (BM) samples from 50 childhood B-precursor ALL patients by IgH/TCR
      delta PCR. Twenty-two patients remained in continuous complete remission (median
      follow-up 61 months), and 28 experienced relapse (median follow-up 75 months).
      Initial regression of MRD on therapy correlated with outcome. At the end of
      induction therapy 2/18 (11.1%) patients from the CCR group were PCR positive vs
      10/16 (62.5%) from the 'relapse' group (P = 0.005). The presence of PCR
      detectable MRD predicted event-free survival independent of standard clinical and
      cytogenetical parameters. Also subsequent to first BM relapse, a correlation
      between MRD regression and outcome was observed. Six of eight patients who became
      PCR negative in the time period between relapse and bone marrow transplantation
      are in CCR, whereas 7/7 patients who remained PCR positive in this time period
      died (P = 0.006). In approximately 70% of evaluable patients, clinical relapse
      was preceded by recurrence of detectable MRD at time intervals of 3-18 months
      earlier and the recurrence of PCR positivity after a period of negativity was
      always followed by overt relapse. At relapse, the combined use of IgH and TCR
      delta probes reduced false negativity caused by clonal evolution to approximately
      10%. This study shows that the evolution of PCR detectable MRD is an independent
      predictor of outcome.

PMID- 7564518
TI  - Analysis of CD7 expression in acute myelogenous leukemia: martingale residual
      plots combined with 'optimal' cutpoint analysis reveals absence of prognostic
      significance.
AB  - Conflicting results exist regarding the prognostic importance of CD7 expression
      in acute myelogenous leukemia (AML). Differences in the method of determining CD7
      positivity, the antibody used, the therapy administered, and the CD7 level used
      as a cutoff point to reduce it to a binary variable have all been postulated to
      account for the discordant findings. We determined the level of CD7 expression by
      flow cytometric analysis using the Leu9 monoclonal antibody in 331 patients with
      newly diagnosed AML and attempted to determine the impact of CD7 on AML
      prognosis. This study used the same methodology and antibody as three of the four
      studies that reported a positive association between CD7 expression and prognosis
      in AML. Optimal cutpoint analysis was used to divide the population into CD7
      positive (CD7+) (>10.5% expression) and CD7-negative (CD7-) (< 10.5% expression)
      groups with the largest survival difference. At the optimal cutpoint, the
      difference in survival was not statistically significantly different (P = 0.068
      uncorrected, P = 0.244 corrected for optimal cutpoint search). There was a marked
      imbalance in the distribution of favorable cytogenetic abnormalities [t(8;21),
      inversion 16, t(15;17)], with 95% segregating to the CD7- group. Analysis
      excluding patients with favorable cytogenetic abnormalities revealed no
      prognostic importance for CD7 expression (P = 0.24 uncorrected). The response
      rate (CR) and survival experiences of CD7+ and CD7- patients were similar with
      six different regimens. CD7 expression was not a significant independent
      prognostic factor in a Cox regression model that included cytogenetics as a
      predictive variable, but it was marginally significant when cytogenetics was
      excluded. We conclude that regardless of the antibody used, the therapy received,
      or the cutoff point selected to determine CD7 expression, CD7 is not associated
      with response rate, prognosis, or survival in AML. The 'optimal cutoff point
      analysis' utilized in this study has applicability to other biologic parameters
      as well.

PMID- 7564519
TI  - Glutathione-S-transferases pi, alpha, mu and mdr1 mRNA expression in normal
      lymphocytes and chronic lymphocytic leukemia.
AB  - Chronic B cell lymphoproliferative disorders are frequently sensitive to
      alkylating agents. To assess the glutathione-S-transferases (GSTs) gene
      expression in B tumoral lymphocytes, possibly responsible for this sensitivity,
      we developed a sensitive RT-PCR assay for the three isoenzymes GST pi, GST mu and
      GST alpha mRNA. Normal B and T lymphocytes from 11 blood donors were separated by
      magnetic beads and tested with this assay. The GST pi was the most abundant
      transferase, and was detected in all B and T cell samples. GST mu was
      undetectable ('null' phenotype) in 6/11 normal donors, either in B or T cells.
      GST alpha was very stable from donor to donor, and was highly correlated between
      B and T cells of the same individual (P < 0.0001). There is no correlation
      between the three isoenzymes, and between each isoenzyme and mdr1 gene
      expression. Twenty-three B lymphoproliferative disorders (20 B-CLL, 3 CD5-
      chronic lymphoproliferative syndromes) were tested with the same technique. An
      average decrease of 57% of the GST pi expression was noted in the mononuclear
      cells of these patients (P < 0.02), with no differences between the untreated and
      treated cases. The GST alpha and mdr1 mRNA levels did not differ from normal B
      lymphocytes, but the proportion of patients with no detectable expression of GST
      mu is lower than in the control (13%). Interestingly, the low content of GST pi
      in B-CLL could explain the frequent sensitivity of this disease to alkylating
      agents.

PMID- 7564521
TI  - Incidence and characteristics of clonal hematopoiesis in remission of acute
      myeloid leukemia in relation to morphological dysplasia.
AB  - We studied 34 patients in remission of acute myeloid leukemia (AML) by performing
      clonal analysis of peripheral blood polymorphonuclear (PMN) cells and mononuclear
      (MN) cells, using X-linked DNA polymorphisms, in conjunction with the assessment
      of morphological myelodysplastic changes, performed by a scoring method. Nine
      patients demonstrated a non-random or skewed X-chromosome inactivation pattern in
      PMN cells. Three of these nine patients had an apparently random pattern in MN
      cells (group A), whereas the remaining six patients demonstrated no difference
      between the inactivation patterns of PMN and MN cells (group B). The PMN cells of
      the other 25 patients showed a random X-chromosome inactivation pattern, and the
      patterns of the PMN cells did not differ from those of the MN cells (group C).
      The scores for myelodysplasia were high (> or = 4) in all three patients in group
      A, intermediate (2-3) in two patients and low (score < 2) in four patients in
      group B, and intermediate in five patients and low in 20 patients in group C. The
      duration of remission in patients with a myelodysplasia score of > or = 2 was
      significantly shorter than that of patients with a score of < 2 (P < 0.01). We
      conclude that clonal remission actually occurs with myelodysplastic features in
      some patients with AML (around 10%, group A). It is possible that this clonal
      analysis may not be sensitive enough to detect the preleukemic clone with
      myelodysplastic features when this clone constitutes only a minor population of
      remission hematopoiesis. To further elucidate the biology of such preleukemic
      clones it is essential to develop more sensitive molecular methods for the
      detection of genetic abnormalities specific to preleukemic hematopoiesis.

PMID- 7564520
TI  - Histological conversion of follicular lymphoma with structural alterations of
      t(14;18) and immunoglobin genes.
AB  - About half of the patients with follicular lymphoma will develop an aggressive B
      cell lymphoma with morphological changes in growth pattern and cellular
      morphology. Changes of the immunophenotype, especially of the expression of
      immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples
      of two patients with follicular lymphoma who developed tumor progression, were
      studied by Southern blot analysis for rearrangements of the Ig genes and the
      oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene
      rearrangements, especially of the Ig light-chain genes, and the structure of the
      t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine
      restriction mapping, remained unaltered with time. However, both within the
      functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive
      secondary alterations took place. This indicates clonal evolution rather than the
      appearance of an independent lymphoma. In the first case with progression from
      follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations
      were especially present 3' of the t(14;18) breakpoint. In the second patient with
      a change from follicular to diffuse centroblastic lymphoma 4 years after
      diagnosis, subsequent class switches from IgM to IgG and to defective IgH
      expression were accompanied by deletion of C mu sequences and a rearrangement of
      the MYC gene, respectively. Additionally, in both patients alterations in
      individual restriction sites occurred, which most likely were due to somatic
      mutations within both the functional IgH and translocated allele. Our data
      indicate that complex alterations of both the functional and non-functional IgH
      allele may accompany tumor progression and may erroneously suggest the appearance
      of independent clones by Southern blot analysis. It remains to be established
      whether these alterations are causative events or the consequence of genetic
      instability and clonal evolution.

PMID- 7564522
TI  - Differentiation of U937 myelomonocytic cell line by all-trans retinoic acid and
      1,25-dihydroxyvitamin D3: synergistic effects on tissue transglutaminase.
AB  - We studied tissue transglutaminase (TGase) expression in human myelomonocytic
      leukemia cells treated by combinations of all-trans retinoic acid (RA) and 1,25
      dihydroxyvitamin D3 (VD). We found that in U937 cells, as in HL-60 and THP-1
      cells, RA alone caused an early induction of enzyme activity, correlated with
      increased mRNA expression. VD alone also induced rapid TGase mRNA expression but
      in this case TGase enzymatic activity was not measurable until 96 h following
      onset of treatment. Combinations of both agents had no additional effects over
      those of RA alone on HL-60 cells, THP-1, and U937 cells during the first 48 h.
      However, following further incubation, U937 cells expressed increased levels of
      TGase when treated by both agents. By many criteria, including their sensitivity
      to various inducers of oxidative burst, lipopolysaccharide-induced production of
      monokines and in the present work, lysozyme secretion and TGase expression, U937
      cells exposed to combinations of RA and VD exhibit a behavior different from
      those of HL-60 and THP-1 cells. They represent a type of leukemia cell amenable
      by this treatment to a stage close to that of a terminally differentiated
      macrophage.

PMID- 7564524
TI  - Successful in vitro purging of leukemic blasts from marrow by cortivazol, a
      pyrazolosteroid: a preclinical study for autologous transplantation in acute
      lymphoblastic leukemia and non-Hodgkin's lymphoma.
AB  - An important new approach to curative treatment of leukemia is vigorous treatment
      of autologous marrow to remove residual abnormal cells in vitro prior to
      reinfusion. This in vitro 'purging' must destroy the malignant cells while
      preserving sufficient normal precursors to allow re-establishment of normal in
      vivo function. We have confirmed that cortivazol (CVZ), a glucocorticoid with an
      unusual structure, can kill dexamethasone (DEX)-resistant leukemic cells and have
      examined its ability to purge DEX-sensitive (CEM-C7) and -resistant (ICR-27)
      human leukemic blasts artificially mixed with normal marrow mononuclear cells in
      vitro. By carefully defining time and dose, we established a 'therapeutic window'
      that allowed 'cure' of the artificial remission marrow. A sufficient number of
      viable normal myeloid precursor cells (CFU-GM) remained to suggest that normal
      marrow precursors adequate for successful marrow transplantation could survive
      such treatment. CVZ could be a useful drug for in vitro purging of bone marrow
      for autologous transplantation in patients with acute lymphoblastic leukemia or
      non-Hodgkin's lymphoma, sensitive or resistant to standard glucocorticoid.

PMID- 7564523
TI  - Adult T cell leukemia following HTLV-I-associated myelopathy/tropical spastic
      paraparesis: case reports and implication to the natural course of ATL.
AB  - Adult T cell leukemia (ATL) is the T cell malignancy caused by human T
      lymphotropic virus type I (HTLV-I), and HTLV-I is also the causative agent of
      HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although
      HTLV-I causes both diseases, concomitant occurrence is reported to be rare. This
      paper describes two cases of HAM/TSP that developed into lymphoma-type ATL after
      the onset of HAM/TSP. In one case, the same HTLV-I infected clone could be
      detected by polymerase chain reaction in peripheral blood obtained when the
      patient was diagnosed as HAM/TSP. This finding showed that the HTLV-I clone
      already existed at the stage of HAM/TSP. Since frequent detection of clonal
      proliferation of HTLV-I infected cells has been reported previously in patients
      with HAM/TSP, careful follow-up is needed for patients with HAM/TSP.

PMID- 7564525
TI  - Detection of evolving immunoglobulin heavy-chain gene rearrangements in acute
      lymphoblastic leukemia: a PCR-based assay employing overlapping DJH primers.
AB  - The use of the polymerase chain reaction (PCR) to amplify clonal immunoglobulin
      heavy-chain (IgH) gene rearrangements appears to be a particularly promising
      technique for detecting minimal residual disease (MRD). However, a major obstacle
      to successful implementation of this technique involves the problem of clonal
      evolution, in which instability of the VHDJH region leads to the generation of
      further rearrangements of the IgH gene over time. Such clonal evolution results
      in a high likelihood of false negative results when detecting MRD using clone
      specific primers based on the rearrangement present at diagnosis. Since in acute
      lymphoblastic leukemia (ALL), clonal evolution commonly involves alterations of
      the VHD joining but not the DJH joining, we have devised a novel PCR strategy to
      circumvent the problem of false negativity in these evolved leukemias. The
      strategy, which involves construction of overlapping clone-specific DJH primers
      for use with a consensus VH segment primer, can be used to amplify both evolved
      and nonevolved ALL populations with high sensitivity and specificity. The method
      does not require radioactivity and should prove valuable for improving the
      effectiveness of PCR-based detection of residual leukemia.

PMID- 7564527
TI  - Molecular characterization of an unusual variant t(15;17) detected in an APL
      patient.

PMID- 7564526
TI  - Proposals for the immunological classification of acute leukemias. European Group
      for the Immunological Characterization of Leukemias (EGIL).
AB  - Criteria for the immunological classification of acute leukemias are proposed by
      a recently established European group designated EGIL. The main aims of EGIL are
      to establish guidelines for the characterization of acute leukemias based on
      marker expression and provide a uniform basis for the diagnosis of the various
      types of these hemopoietic malignancies which should be helpful for future
      multinational clinical and laboratory investigations. Within the two major types
      (B and T cell lineage) of acute lymphoblastic leukemia (ALL), several groups are
      delineated according to the degree of cell differentiation. Within the acute
      myeloid leukemias (AML), only three subtypes as defined by the FAB
      classification: M0-AML, M6-AML and M7-AML, can be unequivocally defined by
      immunological markers; prospective studies are undertaken to see whether
      characteristic immunological profiles are associated with particular AML subtypes
      defined by specific cytogenetic abnormalities. Criteria for the definition of
      biphenotypic acute leukemia (BAL) are devised and a scoring system is outlined
      aimed to distinguish BAL from those acute leukemias with expression of a marker
      from another lineage. In addition, an uncommon subset of acute leukemias with no
      evidence of lymphoid or myeloid differentiation is recognized and the useful
      panel of markers to investigate and establish the cell nature of the acute
      leukemias is outlined. EGIL will focus in the future on testing the
      reproducibility of the proposed guidelines, particularly those for BAL, assessing
      their clinical value within a framework of multicentric trials and setting up
      uniform methodological criteria.

PMID- 7564528
TI  - Low frequency of RAS gene mutations and absence of mutations within the FLR exon
      of NF1 in patients with therapy-related leukemias.

PMID- 7564530
TI  - Binding of BCR/ABL junctional peptides to major histocompatibility complex (MHC)
      class I-B35 molecules: relationship between antigen defective cell lines and HLA
      frequencies in CML patients.

PMID- 7564529
TI  - P170-related multidrug resistance. Enhancement of idarubicin content in leukemic
      cells with cyclosporin in vivo: a report of two cases.

PMID- 7564531
TI  - A novel type of MLL/AF10 fusion transcript in a child with acute megakaryocytic
      leukemia (AML-M7)

PMID- 7564532
TI  - Concomitant complete remission of APL and smoldering ATL following ATRA therapy
      in a patient with the two diseases simultaneously.

PMID- 7564533
TI  - Nurses find rewards with Haitian poor.

PMID- 7564534
TI  - Advanced practice nursing--a look at four Maine nurses.

PMID- 7564535
TI  - Study of women in Maine's economy finds many living on the edge.

PMID- 7564537
TI  - Noninvasive evaluation of the hemodynamically unstable patient: the advantages of
      seeing clearly.

PMID- 7564536
TI  - Smoking in Russia: what do Stalin and Western tobacco companies have in common?

PMID- 7564540
TI  - BLB oxygen mask and aviation.

PMID- 7564539
TI  - Approach to the diagnosis of sarcoidosis.

PMID- 7564538
TI  - The elusive role of atrial natriuretic peptide in hypertension.

PMID- 7564541
TI  - Dr. Walter C. Alvarez at Mayo.

PMID- 7564542
TI  - Role of transesophageal echocardiography in hemodynamically unstable patients.
AB  - OBJECTIVE: To evaluate the clinical impact of transesophageal echocardiography on
      subsequent management and outcome in hemodynamically unstable patients with
      suspected cardiovascular pathologic conditions. DESIGN: We reviewed data on
      patients with hemodynamic instability (hypotension, shock, or pulmonary edema)
      who underwent transesophageal echocardiography between December 1987 and May
      1994. MATERIAL AND METHODS: A total of 127 patients (70 male and 57 female
      patients with a mean age of 68 years) underwent transesophageal echocardiography
      at our institution as part of the diagnostic procedures used to evaluate unstable
      hemodynamics. RESULTS: No clinically significant complication was encountered
      during the procedure; transesophageal echocardiographic imaging was inadequate in
      three patients (2%). Of the 124 patients with adequate images, transesophageal
      echocardiography disclosed a severe cardiovascular abnormality responsible for
      the unstable hemodynamics in 65 patients (52%), and 26 patients (21%) underwent
      urgent pericardiocentesis or a cardiac surgical procedure, primarily based on
      transesophageal echocardiographic findings. CONCLUSION: Transesophageal
      echocardiography can be safely performed in hemodynamically unstable patients, it
      produces a high diagnostic yield, and it provides important information for
      prompt therapeutic decision making. Therefore, we recommend transesophageal
      echocardiography as one of the initial diagnostic procedures in critically ill
      patients suspected of having an underlying cardiovascular disorder.

PMID- 7564543
TI  - Atrial natriuretic peptide and blood pressure in a population-based sample.
AB  - OBJECTIVE: To assess the relationship of plasma atrial natriuretic peptide (ANP)
      levels with blood pressure levels and the occurrence of hypertension in a large
      population-based sample. DESIGN: We performed a cross-sectional study of the
      relationship between ANP levels and blood pressure levels, diagnosis of
      hypertension, and family history of hypertension in Caucasians from Rochester,
      Minnesota. MATERIAL AND METHODS: Plasma ANP and blood pressure levels were
      measured in 1,338 Caucasian subjects who were members of 301 three-generation
      families from the population of Rochester. Hypertension was defined as systolic
      blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or
      more. Each subject in the parental generation was categorized as having zero,
      one, or two parents with hypertension. Analyses were done separately for each
      generation and gender stratum. RESULTS: Within gender and generation strata, we
      noted no consistent pattern of positive or negative correlation of plasma ANP
      levels with systolic blood pressure, diastolic blood pressure, or heart rate.
      Within the grandparental generation, mean plasma ANP levels did not differ
      between those with normal blood pressure and those with hypertension. In the
      parental generation, mean plasma ANP levels did not differ between subjects with
      zero, one, or two parents with hypertension. CONCLUSION: In Caucasians,
      interindividual differences in plasma ANP levels are not associated with
      interindividual differences in blood pressure levels, the diagnosis of
      hypertension, or family history of hypertension.

PMID- 7564544
TI  - Cervical disk prolapse.
AB  - OBJECTIVE: To correlate the findings on computed tomographic myelography (CTM)
      with surgically and pathologically proven prolapsed cervical disks, mention other
      pertinent cross-sectional imaging studies, and note the clinical relevance of
      certain CTM features. DESIGN: We retrospectively reviewed the medical and
      radiologic records of Mayo patients with suspected degenerative cervical disk
      disease during a 4-year period. MATERIAL AND METHODS: Between January 1986 and
      December 1989, 734 patients with possible cervical disk disease underwent
      assessment by CTM. An extruded disk was noted in 297 of these patients. In this
      study group, magnetic resonance (MR) imaging was also done in 28 patients and
      plain computed tomography was performed in 14, and we summarized those findings.
      RESULTS: Of the 297 study patients, 280 had a cervical radiculopathy and 17 had a
      myelopathy. CTM identified more than 90% of the extruded cervical disks. CTM
      could not distinguish between an osteophytic cartilaginous cap and a disk, and
      CTM could not identify the source of a cervical radiculopathy in 102 patients.
      Although only a few imaging studies other than CTM were performed, those
      modalities were less sensitive in the detection of prolapsed disks. CONCLUSION:
      Imaging of cervical disk prolapse continues to be difficult, and the results are
      not always specific. CTM is the most sensitive imaging examination, but the
      number of MR studies in the current series of patients was insufficient for a
      reasonable comparison between the two modalities.

PMID- 7564545
TI  - Werner Arber--Nobel laureate.

PMID- 7564546
TI  - Mediastinal parathyroid cysts.
AB  - OBJECTIVE: To present our experience with mediastinal parathyroid cysts and
      summarize previously reported cases. DESIGN: We retrospectively reviewed medical
      records and reviewed the pertinent literature. MATERIAL AND METHODS: The
      clinical, operative, and pathologic findings in 7 cases of mediastinal
      parathyroid cysts encountered at one institution and 31 cases previously reported
      in the literature are described. RESULTS: Rarely, cysts may arise from an
      aberrant mediastinal parathyroid gland. Such cysts may manifest as a symptomatic
      mass, as an asymptomatic finding on roentgenography, or during the assessment of
      a patient with hyperparathyroidism. The diagnosis may be made by fine-needle
      aspiration or by excision and pathologic examination. CONCLUSION: Functioning
      parathyroid cysts represent degeneration of a hyperfunctioning gland, such as an
      adenoma, and are usually removed through a cervical approach. Nonfunctioning
      cysts in asymptomatic patients with normal serum calcium levels are considered
      indeterminate and should be managed accordingly. Excision is usually recommended.

PMID- 7564548
TI  - Heart rate variability: technique and investigational applications in
      cardiovascular medicine.
AB  - OBJECTIVE: To describe heart rate variability (HRV) analysis, especially time-
      and frequency-domain analyses, and some of its investigational applications in
      clinical cardiovascular medicine. DESIGN: We provide a brief introduction to the
      magnitude of sudden cardiac death and the factors that influence life-threatening
      ventricular arrhythmias as a backdrop to the potential importance of the
      autonomic nervous system and how this system might be assessed by the analysis of
      HRV. MATERIAL AND METHODS: We reviewed the literature from 1973 to 1994 that
      described beat-to-beat changes in heart rate, heart rate signal recording and
      processing, and investigational applications of HRV analysis to cardiovascular
      medicine. RESULTS: Beat-to-beat changes in heart rate are partly influenced by
      the autonomic nervous system. Briefly, changes in sympathetic input to the
      sinoatrial node affect low-frequency HRV, whereas changes in parasympathetic
      input affect high-frequency HRV. Multiple physiologic and nonphysiologic
      determinants of HRV exist, and therefore analysis of HRV as a direct "window" to
      autonomic tone is problematic. CONCLUSION: In selected patient populations,
      analysis of HRV yields important information about sinoatrial responsiveness to
      autonomic input and mortality risk stratification. Routine application of HRV
      analysis to clinical cardiovascular medicine awaits further investigation,
      however.

PMID- 7564547
TI  - Utility of a "swish and spit" technique for the collection of buccal cells for
      TAP haplotype determination.
AB  - OBJECTIVE: To demonstrate the utility of a "swish and spit" technique as a
      nucleated cell source for transporter associated with antigen processing (TAP)
      haplotype determination by molecular methods in large-scale clinical trials.
      DESIGN: Twenty normal volunteers were recruited for this prospective feasibility
      study. From each subject, buccal or blood cells (or both) were collected for use
      in TAP haplotype assignment by molecular methods and subjected to various storage
      conditions. MATERIAL AND METHODS: As an alternative to use of lymphocytes
      obtained by venipuncture, we developed a swish and spit technique for collecting
      buccal cells for assigning TAP haplotype. For this technique, the subject
      vigorously swishes isotonic saline in the mouth and expectorates it into a
      collection container. DNA is extracted from the buccal cells by proteinase K
      digestion, phenol-chloroform extraction, and ethanol precipitation. In addition,
      we compared DNA extracted from mouthwash specimens stored under various
      conditions to which a specimen might be exposed if mailed. RESULTS: DNA extracted
      from buccal cells obtained by the swish and spit technique provided excellent
      templates for the polymerase chain reaction (PCR), and subject acceptance of this
      method was universal. In all cases, assigning TAP haplotype by PCR amplification
      of specific alleles with use of buccal or blood-derived specimens was successful.
      The integrity of the specimens was unaffected by storage at -20 degrees C, 4
      degrees C, 25 degrees C, or 37 degrees C, and we were able to use the DNA from
      cells stored under any of these conditions for TAP haplotying. CONCLUSION: We
      conclude that DNA from buccal cells collected by the swish and spit technique for
      TAP haplotype assignment is an excellent substitute for DNA obtained from
      nucleated blood cells, and the technique is useful for large-scale clinical
      studies that require DNA from subjects geographically distant from the research
      site.

PMID- 7564549
TI  - Transverse vaginal septum associated with tubal atresia.
AB  - Transverse vaginal septum is a defect of vertical fusion during embryogenesis of
      the vagina. The estimated incidence is 1 per 30,000 to 84,000 women. It is
      infrequently associated with genitourinary tract, gastrointestinal tract,
      musculoskeletal, and cardiac malformations. Previous reports of transverse
      vaginal septum have included unilateral absence of the fallopian tube and ovary
      and absence of the proximal portion of the fallopian tube. This report describes
      bilateral tubal atresia associated with a transverse vaginal septum. A 17-year
      old nulligravida sought medical assessment because of primary amenorrhea and
      cyclic pelvic pain. Physical examination revealed a blind vaginal pouch and a
      tender pelvic mass. Radiologic studies showed a transverse vaginal septum 1.5 cm
      distal to the cervix. The septum was resected with laparoscopic guidance, and
      bilateral fallopian tubal atresia was noted. The pelvis was otherwise normal.
      Patients commonly have a pelvic or abdominal mass, pain, and amenorrhea at time
      of expected menarche. Surgical resection is the treatment of choice.
      Postoperative dilation may be necessary to prevent restenosis. Outlook for
      pregnancy is encouraging despite a higher than normal incidence of spontaneous
      abortion and endometriosis in such patients.

PMID- 7564550
TI  - Castleman's disease.
AB  - OBJECTIVE: To describe the two variants of Castleman's disease--the hyaline
      vascular type and the plasma-cell type--and discuss the associated histologic
      features. DESIGN: We present a case of the hyaline-vascular type and review the
      literature. RESULTS: Castleman's disease was once thought to be localized and
      self-limited, but in recent years, reports have described a multicentric variety
      with severe systemic manifestations and, at times, an inexorable clinical course.
      Unlike the localized type for which surgical excision is curative regardless of
      the histologic type, multicentric disease often necessitates aggressive systemic
      therapy and portends a poor outcome. Little is known about the cause of this
      disorder, but the bulk of evidence points toward faulty immunoregulation that
      results in excessive proliferation of B lymphocytes and plasma cells in lymphoid
      organs. CONCLUSION: Castleman's disease is rare and poorly understood. The
      diagnosis is "contextual" and must be considered in the appropriate clinical
      setting and only after all other causes of lymphadenopathy have been investigated
      and excluded. The optimal therapeutic regimen is unknown.

PMID- 7564551
TI  - Treatment options for osteoporosis.
AB  - The number of women affected by postmenopausal osteoporosis is likely to continue
      to increase substantially as the population ages. Furthermore, the therapeutic
      options for such patients are likely to increase. In this brief review, we
      outline the use of the currently available medications for the management of
      osteoporosis--namely, estrogen, calcitonin, calcium, and vitamin D. In addition,
      we discuss the next generation of drugs that are likely to become available in
      the future--the bisphosphonates and estrogen analogues. As these options become
      available, the prevention and treatment of osteoporosis will become similar to
      the management of other common disorders such as hypertension or hyperlipidemia,
      in which the most appropriate medication may differ for individual patients.
      Thus, the treatment of osteoporosis is likely to evolve from a decision of
      whether to initiate estrogen replacement therapy to a more complex decision of
      the best agent to use for an individual patient.

PMID- 7564552
TI  - 27-year-old woman with fever, increased bilirubin level, and thrombocytopenia.

PMID- 7564554
TI  - Delirium in elderly patients: evaluation and management.
AB  - OBJECTIVE: To review the evaluation and management of delirium in elderly
      patients for primary-care providers. DESIGN: We summarize the clinical features,
      course, pathophysiologic aspects, predisposing factors, causes, and differential
      diagnosis of delirium and discuss approaches to affected patients and various
      management strategies. RESULTS: Delirium, an altered mental state, occurs more
      frequently in elderly than in younger patients. The pathophysiologic changes
      associated with aging and the higher occurrence of multiple medical problems and
      need for medications contribute to the higher frequency of delirium in elderly
      patients. Evaluation should begin with a consideration of the most common causes,
      such as a change in or addition to prescribed medications, a withdrawal from
      alcohol or other sedative-hypnotic drugs, an infection, or a sudden change in
      neurologic, cardiac, pulmonary, or metabolic state. Finally, management of
      delirium is threefold: (1) identifying and treating underlying causes, (2)
      nonpharmacologic interventions, and (3) pharmacologic therapies to manage
      symptoms of delirium. CONCLUSION: Elderly patients frequently experience
      delirium. Delirious symptoms can produce devastating consequences if they are not
      recognized and appropriately treated.

PMID- 7564553
TI  - Initial assessment of infants and children with suspected inborn errors of
      metabolism.

PMID- 7564557
TI  - Chromosomal analysis in young vs. senescent human fibroblasts by fluorescence in
      situ hybridization: a selection hypothesis.
AB  - Almost all previous studies on chromosomal analysis related to in vitro aging of
      human fibroblasts were done using only metaphase chromosomes. However, this
      procedure may provide only partial information since the aneuploidy presumably
      hidden in interphase cells would remain undetected. For this reason, we have
      analyzed aneuploidy both at interphase and at metaphase. Female (IMR-90) and male
      (IMR-91) cells were grown from the lowest to the highest population doubling
      levels and aneuploidy analysis was done by FISH with alpha-satellite DNA probes
      of 15 autosomes and two sex chromosomes. Our data on total aneuploidy in young
      cells indicate that significantly higher proportions of cells with aneuploidy can
      be detected at interphase than at metaphase. This presumably indicates that
      during active division of young cells, more aneuploid than diploid cells are
      selected against entry to mitosis. In contrast, interphase senescent cells from
      both strains show significantly fewer aneuploid nuclei than do young cells at
      interphase. This probably indicates that during senescence, there is greater
      selective pressure in the culture against long-term survival of aneuploid cells
      than against survival of diploid cells. Our study shows that cellular dynamics
      with respect to aneuploidy involving various chromosomes differs significantly at
      interphase and at mitosis during in vitro aging of human fibroblasts, and we
      propose a 'Selection Hypothesis' as an explanation to our findings.

PMID- 7564555
TI  - Recognition and management of anxiety and depression in elderly patients.
AB  - OBJECTIVE: To describe important aspects of the recognition and management of
      anxiety and depression in elderly patients. DESIGN: We reviewed pertinent recent
      articles in the medical literature and compiled guidelines for diagnosing and
      treating anxiety and depression in the geriatric population. RESULTS: Depression
      and anxiety are common in the elderly population. The development of depression
      in elderly subjects is associated with a higher risk of death from suicide than
      for any other age-group. Recognition of depression in elderly patients is often
      hampered by an inability or reluctance on the part of these patients to report
      depressive symptoms. In addition, anxiety and depression are often attributed to
      organic illness in this age-group. Pharmacotherapy is effective; however, older
      patients are probably more likely than young patients to experience adverse
      effects. Using medications at lower doses, choosing drugs with shorter half
      lives, and avoiding drugs with potent anticholinergic side effects are often
      advisable. CONCLUSION: Anxiety and depression are common conditions among the
      elderly population. Correct recognition, attention to underlying precipitating
      factors, and compassionate, supportive care can vastly improve the quality of the
      lives of these patients.

PMID- 7564556
TI  - Neurochemical changes related to ageing in the senescence-accelerated mouse brain
      and the effect of chronic administration of nimodipine.
AB  - The levels of neurotransmitters and related metabolic enzyme activities in the
      brain of young-adult (3 months old), aged (11 months old) and nimodipine
      administered (11 months old) senescence-accelerated mouse (SAM) were compared.
      Nimodipine, a calcium antagonist, was administered orally for 5 months.
      Acetylcholine (ACh), serotonin (5-HT) and dopamine (DA) levels all decreased with
      age but this decrease was attenuated by nimodipine. Choline acetyltransferase and
      choline esterase activities increased with age, and nimodipine enhanced their
      activities. Tryptophan hydroxylase activity was not affected by age or nimodipine
      administration. Monoamine oxidase-A activity increased with age, and was
      decreased by nimodipine administration. These results suggest that SAM rapidly
      undergoes neurochemical changes which are considered to be part of the normal
      aging process, and these changes were attenuated by chronic administration of
      nimodipine.

PMID- 7564558
TI  - The proliferative response and anti-oncogene expression in old 2BS cells after
      growth factor stimulation.
AB  - The limited replicative lifespan of diploid human cells in vitro (cellular
      senescence) serves as a cellular model of aging. We examined the proliferative
      response of 2BS cells of different population doubling levels to fibroblast
      growth factor (FGF). DNA synthesis was measured by thymidine incorporation. As
      the cells aged, there was a significant decrease in the stimulation of DNA
      synthesis by FGF addition (P < 0.01). The effective concentration of FGF and the
      latent period prior to DNA synthesis did not change. Expression of Rb and p53
      mRNA after growth factor stimulation was also examined. Young and old cells had
      similar Rb mRNA levels, whereas the p53 mRNA level was significantly reduced in
      old cells. After both cells were treated by FGF or epidermal growth factor (EGF),
      Rb expression increased 210-275% in young cells and 50-60% in old ones. However,
      no significant change was found in p53 gene transcriptions after FGF addition.
      The results further suggest that cell aging is associated with a progressive loss
      of the ability of cells to respond to growth factors.

PMID- 7564559
TI  - Brassinolide is a selective ribosomal cistron regulator in onion leaf base
      tissue.
AB  - Outer epidermal cells from the basal, equatorial, near-apical, and apical regions
      of the third turgid onion (Allium cepa L. var. yellow, sweet Spanish) leaf base
      were treated (3 and 6 h in the dark = T3 and T6, respectively) with brassinolide
      (Br, a brassinosteroid plant growth regulator; effects on excised pieces compared
      with those in water controls: there were no statistical differences between the
      T3 and T6 results). Br induced increases in the volume and changes in
      morphologies of the major nucleoli to a greater extent than observed for major
      nucleoli in basal through near-apical controls. No major nucleoli were activated
      in control or Br-treated apical tissue. Minor nucleolar organizer regions in
      control and Br-treated tissue remained inactive in all locations. We propose that
      Br is a major ribosomal cistron regulator.

PMID- 7564560
TI  - Influence of aging and neurodegenerative disease on changes in band 3-like
      proteins in white blood cells.
AB  - Fluorescent microspheres were used to measure antibody-induced capping of
      leukocyte membrane proteins that are immunologically related to band 3, the anion
      exchanger of the erythrocyte. The degree of capping was found to increase with
      donor age. Surface labeling and capping characteristics of cells from healthy,
      age-matched controls were not different from those from patients with Alzheimer's
      disease, multi-infarct dementia, and Down's syndrome. Immunoblots, however,
      indicated increased expression and/or breakdown of band 3-like proteins in
      leukocytes from patients when compared with young and old control donors. These
      findings emphasize the possible involvement of band 3-like proteins of nucleated
      cells in aging and disease.

PMID- 7564561
TI  - Interrelationship of fever, immune response and aging in mice.
AB  - Fever is the cardinal manifestation of infection and may be blunted in certain
      infected elderly individuals. It is known that elevated body temperature enhances
      both the inflammation response and immune function, resulting in increased host
      resistance to infection. Recently, it has been suggested that the elevation of
      body temperature and the activation of lymphocytes by IL-1 are interrelated host
      effects. However, the question of whether fever response in vivo is closely
      correlated to cell-mediated immune parameters is unknown. In this study, a well
      defined murine model was used to study the relationships between aging, fever and
      cell-mediated immune response. Thus, measurements of rectal temperature changes
      were made in individual young (4-6 months) and old (26-27 months) BALB/c mice to
      determine their ability to respond to endogenous pyrogen (recombinant IL-1).
      Splenic cells from these animals were used to assess T- and B-cell proliferation,
      production of interleukin 1 (IL-1) and IL-2. The results revealed that the
      proliferative capacity and the IL-1 and IL-2 producing capacity of splenic cells
      from old mice were markedly decreased. However, aging did not significantly
      affect the mean febrile responses in old mice following rIL-1 injections.
      Finally, there was no significant correlation between in vivo fever responses and
      the immune parameters measured in vitro in both young and old mice.

PMID- 7564563
TI  - Role of immune response as determinant of tumor progression in function of host
      age in the B16 melanoma.
AB  - Aging constitutes the major cause for the development of most neoplastic
      diseases. However, tumors in aged people present with a lower degree of
      aggressiveness than in young patients. The reasons for this paradoxical behavior
      are not clear. We attempted to verify whether the immune system has a role in the
      relation between host age, immune response and tumor progression. We compared the
      growth rate of B16 melanoma and a highly malignant variant, the B16/Col/R, in
      young and aged mice that have or have not undergone splenectomy. The following
      results were obtained: (1) Splenectomy stimulated growth in the parental melanoma
      in both young and aged mice, indicating a protective role of the spleen against
      this tumor at all ages; (2) Spleen ablation provoked inhibition of the highly
      metastatic variant growth in young mice, suggesting a stimulatory role of the
      spleen in this case; (3) By contrast, in aged mice inoculated with the B16/Col/R
      variant, splenectomy enhanced tumor growth, indicating a defensive role of the
      spleen. Age favors a positive host response against the aggressive clone of the
      melanoma. Differential host response in young versus aged mice can explain, in
      this tumor system, the difference in tumor progression rate as a function of age.

PMID- 7564564
TI  - Changes in the plasmatic membrane characteristics during microsomal monooxygenase
      induction in the liver of adult and old rats.
AB  - The experiments on adult (6-8 months) and old (24-26 months) male Wistar rats
      have shown that treatment of animals with phenobarbital results in a significant
      increase in hepatic microsomal enzyme content, plasmatic membrane Na+, K(+)
      ATPase activities and the elevation of hepatocyte membrane potential value. It is
      presumed that the changes in plasmatic membrane characteristics during microsomal
      monooxygenase induction are related to the synthesis of specific intracellular
      factors (invertors). This assumption was verified by the experiments with
      'cellular hybrid' system (cytosol--plasmatic membranes). Using this cross
      systems, it was shown that the hepatocyte cytosol of rats treated with
      phenobarbital produced Na+, K(+)-ATPase activity. The extent of Na+, K(+)-ATPase
      activation was essentially lower when cytosol derived from old rat hepatocytes
      was used. The presence of specific factors that activated Na+, K(+)-ATPase in
      hepatocyte plasmatic membrane was also discovered in blood serum of induced adult
      and old rats.

PMID- 7564562
TI  - Restriction and functional changes of dopamine release in rat striatum from young
      adult and old rats.
AB  - In order to investigate the age-related changes in dopaminergic activity in rats,
      we have utilized the K(+)- and veratridine-stimulated [14C]dopamine release from
      striatum in vitro as a functional index of responsiveness to these stimuli in
      aging. We found that the K(+)-stimulated dopamine release from old (12 months)
      rats decreased by more than 50% compared to that from young adult rats (3
      months). Reserpine (5 mg/kg) led to a pronounced decrease of the K(+)-stimulated
      dopamine release of young adult as well as old rats. Whereas ouabain (10 mumol/l)
      decreased the K(+)-stimulated dopamine release from young adult rats, in old rats
      the K(+)-induced dopamine release was increased up to 250%. However, in old rats
      which were reserpine pretreated, ouabain was unable to stimulate the K(+)-induced
      dopamine release. In contrast, the veratridine-stimulated dopamine release of old
      rats was increased up to 200% compared to that of young adult rats and was highly
      sensitive to reserpine pretreatment but not to ouabain. However, reserpine did
      not alter this veratridine-stimulated dopamine release from young adult rats. The
      present data indicate that the age-related reduction of exocytosis-related,
      Ca(2+)-dependent release mechanisms (K+) are probably compensated via an increase
      in Ca(2+)-independent, uptake carrier-mediated release processes (veratridine).

PMID- 7564565
TI  - On the role of the peroxisome in ontogeny, ageing and degenerative disease.
AB  - This article reviews the available data on the role of the peroxisome in the
      growth, differentiation and degeneration of mammalian tissues. Developmental
      progressions of peroxisomes are described, along with the influence of inhibitors
      of peroxisomal enzymes, peroxisome proliferators and morphogenetic agents on the
      ontogeny of experimental animals. The role of the peroxisome in protecting
      tissues from damage by oxygen free radicals is also described, as is the changing
      role of the peroxisome in the ageing animal. Amongst the degenerative diseases
      which have been associated with free radical damage are cancer, atherosclerosis,
      muscular dystrophy, rheumatoid arthritis and the senile degeneration of brain
      function. In all these conditions, the major characteristics of molecular damage
      have been considered, along with the particular role of the peroxisome in
      alleviating these effects. Proposals for further research into peroxisomal
      function during ontogeny and the degenerative changes associated with ageing are
      developed, and the possibility of palliative treatments discussed.

PMID- 7564566
TI  - Developmental expression and corticosterone inhibition of adenosine deaminase
      activity in different tissues of mice.
AB  - The activity expression and corticosterone inhibition of adenosine deaminase
      (ADA) were studied in the spleen, stomach, and liver of mice at various postnatal
      ages. The specific activity of ADA is very low in the spleen and stomach of 5-
      and 10-day-old mice, and increases significantly (2.5- to 3.0-fold) in 20- and 30
      day-old animals. Its level shows a further increase in the spleen of 60-day-old
      mice while stomach increase of ADA is not significant. In contrast, the activity
      of ADA is significantly higher in the liver of 5- and 10-day-old mice, decreases
      markedly (2.5-fold) in 20- and 30-day-old animals and shows a sharp increase in
      the liver of 60-day-old mice. Corticosterone administration brings a marked
      inhibition in the activity of ADA at all ages studied in the spleen and stomach
      whereas it inhibits the liver ADA only at 30 and 60 days postnatal age. These
      findings suggest an age- and tissue-specific expression of ADA activity and also
      indicate corticosterone as an inhibitory regulator of this enzyme.

PMID- 7564567
TI  - Changes in the levels of enzymes which modulate the antioxidant balance occur
      during aging and correlate with cellular damage.
AB  - Oxidative metabolism produces a flux of superoxide anions that must be removed
      from the cellular environment if the cell is to survive. The levels of
      antioxidant enzyme involved in the elimination of superoxide anions and/or
      hydrogen peroxide were investigated in an attempt to correlate any changes in the
      levels of these enzymes during aging with changes in free radical mediated
      cellular damage. Cu/Zn superoxide dismutase (Sod1), glutathione peroxidase (Gpx1)
      and catalase levels were measured in a number of organs during murine aging. Sod1
      enzyme activity rose during aging in all organs studied, while the levels of both
      Gpx1 and catalase showed organ specific profiles. Both organs in which lipid
      peroxidation damage (which was used as a marker of free radical mediated damage)
      increased with age, namely the brain and small intestine, also showed a
      significant increase in the ratio of Sod1 to Gpx1 enzyme activity. In organs
      where either the ratio of Sod1/Gpx1 activity or Sod1/catalase levels (in the lung
      only) ratios were maintained during aging, no increased lipid peroxidation damage
      was detected. In the lung where Sod1/Gpx1 ratio did increase, Sod1/catalase
      remained constant and this was able to provide protection during aging. Thus our
      data shows that alterations in the balance between first and second steps of the
      antioxidant pathway correlate with cellular damage, and that this may contribute
      to the aging changes seen in some organs.

PMID- 7564568
TI  - How long can humans live? Lower bound for biological limit of human longevity
      calculated from Danish twin data using correlated frailty model.
AB  - How long can people live? Opinions of the researchers diverge and debates
      continue. Is there any systematic way to address this question? In this paper, we
      suggest an approach to the estimation of the biological limit of human longevity
      using survival data for twins from different zygocity groups. The approach is
      based on the genetic model of individual frailty. It combines ideas used in
      demography and survival analysis with methods of quantitative genetics and
      genetic epidemiology. The association between the life-spans of related
      individuals is described by the correlated frailty model of bivariate survival. A
      version of this model is used in order to estimate heritability of the individual
      frailty and to calculate the lower bound of human longevity. The limitations of
      this approach and directions of further research are discussed.

PMID- 7564569
TI  - Rapid tyrosine phosphorylation of Grb2 and Shc in T cells exposed to anti-CD3,
      anti-CD4, and anti-CD45 stimuli: differential effects of aging.
AB  - Two adapter proteins, Grb2 and Shc, have recently been implicated in the
      transmission of activation signals from the stimulated T cell receptor to Ras. We
      show here that in vitro stimulation of mouse splenic T cells with crosslinked
      anti-CD3 antibody leads within 30 s to phosphorylation of both Grb2 and Shc.
      Treatment with crosslinked anti-CD45 antibody leads to phosphorylation of Grb2
      and also to a slight retardation in the mobility of this protein in an SDS
      polyacrylamide gel; both changes are seen within 30 s of crosslinking.
      Crosslinked anti-CD4 antibody leads to phosphorylation of Shc and to the
      phosphorylation of a 30-kDa protein that cross-reacts with anti-Grb2 antibodies.
      Aging leads to a decline in CD3-stimulated phosphorylation of Shc (but not Grb2),
      and to an increase in CD4-stimulated phosphorylation of Grb2, Shc, and the 30-kDa
      Grb2-like protein. Increased tyrosine-phosphorylation of Grb2 after exposure to
      either anti-CD3 or anti-CD45 suggests that Grb2 may be a common substrate for
      both CD3-linked kinases and the CD45 phosphatase. The differences between T cells
      from young and old mice suggest that aging may lead to a set of alterations in
      kinase/substrate coupling that contribute to immune dysfunction in the elderly,
      and that activation of the Ras pathway might be impaired by aging in T
      lymphocytes.

PMID- 7564570
TI  - Indenoindole depresses lipofuscin formation in cultured neonatal rat myocardial
      cells.
AB  - Lipofuscin accumulation in cultured rat myocardial cells is considered an index
      of intra-lysosomal oxidative reactions and was registered by autofluorescence
      measurements. Lipofuscinogenesis in secondary lysosomes is thought to be a
      consequence of Fenton reactions, and is much enhanced by oxidative stress
      obtained by culturing the cells in an atmosphere containing 40% oxygen. The
      influence of the synthetic antioxidant indenoindole (DHII), as compared to
      control cells, was a dose-responsive depression of lipofuscinogenesis to a degree
      of 19% and 17% with 20 microM DHII and to 25% and 23% with 40 microM DHII after 7
      and 14 days in culture, respectively. This demonstrates a significant quenching
      of oxidative stress and suggests the therapeutic value of DHII and related
      antioxidants in protecting against oxygen radical-related diseases. It is also
      suggested that neonatal cardiac myocytes in culture are a suitable model system
      for the evaluation of oxygen radical-induced myocardial damage.

PMID- 7564572
TI  - [Nutritional deficiency an unlikely cause of death during sport training].

PMID- 7564571
TI  - Superoxide generation by alveolar macrophages from aged rats: improvement by in
      vitro treatment with IFN-gamma.
AB  - Alveolar macrophages (AM) from aged rats show an impaired oxidative response, but
      it is unclear whether or not this is due to the inability of these cells to be
      activated. To elucidate this, we investigated the capacity of AM from young (16
      week-old) and aged (100-week-old) rats to become primed with recombinant rat
      interferon-gamma (IFN-gamma) for increased phorbol myristate acetate (PMA)
      elicited O2- production, utilizing an MCLA-dependent chemiluminescent assay. We
      also compared concanavalin A- or Bacillus Calmette Guerin (BCG)-induced IFN-gamma
      production by the spleen cells of young and aged animals. The data indicated that
      AM freshly harvested from non-sensitized aged rats produced less O2- than those
      from young animals. A similar result was obtained in BCG-sensitized rats.
      However, AM from aged rats were primed with in vitro treatment with IFN-gamma for
      increased rate of O2- production to an equivalent level of that by AM from young
      animals. In addition, the ability of spleen cells to produce IFN-gamma was well
      maintained in aged rats. These results suggest that AM function is suppressed in
      the lungs of aged animals. Our observation that the decreased AM function in aged
      rats can be reversed is important because it suggests that appropriate treatment
      may reduce the incidence and mortality of respiratory infections in the elderly.

PMID- 7564573
TI  - [Lower mortality after subarachnoid hemorrhage].

PMID- 7564574
TI  - [Angina pectoris is as expensive as myocardial infarction. An unexpected result
      of a study].

PMID- 7564576
TI  - [Subarachnoidal hemorrhage in a perspective of 20 years].

PMID- 7564575
TI  - [Skeletal dysplasia. Medical interdisciplinary care is necessary for optimal
      treatment].

PMID- 7564577
TI  - [A heart-assist device. A life-saving mechanical circulatory support to be used
      while waiting for heart transplantation].

PMID- 7564579
TI  - [Oral selenium therapy against growing pain in children].

PMID- 7564578
TI  - [Expert advice is not expected from everyday practice. Patients on regular check
      ups are often getting sicker with time].

PMID- 7564580
TI  - [Training of clinical skills in undergraduate medical education. Professional
      patients as educators].

PMID- 7564581
TI  - [25th year of the Medical Society's ethics committee. Resources, everyday issues
      should be in focus].

PMID- 7564582
TI  - [Medical ethics should be deeply rooted in everyday health care!].

PMID- 7564583
TI  - [Renaissance of medical ethics?].

PMID- 7564584
TI  - [Comments on criticism of the ethics committee. Embryo transfer is not in the
      best interest of the child].

PMID- 7564586
TI  - [A new classification introduced in Fass (Swedish Drug Index). A simple way for
      assessment of drug interactions].

PMID- 7564585
TI  - [Helicopter landing sites on hospitals in Central Sweden. Only one of 27
      approved].

PMID- 7564587
TI  - [Disappointing expectations in psychiatry. Former mental hospitals better than
      their reputation?].

PMID- 7564588
TI  - [It is unfortunate to make a diagnosis based on news advertisement].

PMID- 7564589
TI  - [Where did surgery disappear?].

PMID- 7564590
TI  - [Questionable therapeutic suggestions in shoulder instability].

PMID- 7564591
TI  - [The cause of health care crisis needs to be discussed!].

PMID- 7564592
TI  - [75 percent sick listing--why?].

PMID- 7564593
TI  - [Combination drugs in the treatment of hypertension. Simpler for patients,
      physicians and pharmacies].

PMID- 7564594
TI  - [Surfactant therapy of fullterm infants. An alternative in meconium aspiration
      and pneumonia].

PMID- 7564595
TI  - [Pancreas resection in cancer. Reduced mortality but morbidity is still high].

PMID- 7564596
TI  - [Life-threatening hemorrhage caused by insertion of pacemakers and central venous
      catheters].

PMID- 7564598
TI  - [Peep-hole techniques may cause biliary tract injury. Risks of laparoscopic
      cholecystectomy].

PMID- 7564597
TI  - [The man behind the rod: John Auer. A broad-minded physiologist].

PMID- 7564599
TI  - [Resistance to activated protein C. A common genetic risk factor in venous
      thrombosis].

PMID- 7564600
TI  - [Oral examination in general practice. Functioning for short-term courses with
      many students].

PMID- 7564601
TI  - [Ambulatory surgery must follow the rules of the game! Strict patient selection
      is important].

PMID- 7564602
TI  - [Are you a professional physician? Consult a professional interpreter!].

PMID- 7564603
TI  - [A report on quality of surgical treatment: no evidence of the fact that bigger
      hospitals are better than small ones].

PMID- 7564604
TI  - [Private health insurance leads to segregated care].

PMID- 7564605
TI  - ["Stan" (cardiotocography) should not be abolished].

PMID- 7564606
TI  - [Statistics too have been hit by strict saving plans].

PMID- 7564607
TI  - [Big weight gain differences between patients on dialysis].

PMID- 7564608
TI  - [Misleading information about patients with palmar sweating].

PMID- 7564609
TI  - [Swedish control of implants is of a high international class].

PMID- 7564610
TI  - [Drug prescription may be influenced by active efforts].

PMID- 7564611
TI  - [Moving the elderly may be a success].

PMID- 7564612
TI  - [Acute renal failure can be prevented. New discoveries on the significance of
      hypoxia in the renal medulla].

PMID- 7564613
TI  - [Emergency readmissions are common within 14 days. A 2-year study at a department
      of internal medicine].

PMID- 7564614
TI  - [Patch tests should be performed by experiences dermatologists. Many allergens
      can cause contact dermatitis].

PMID- 7564616
TI  - [New discoveries on atherosclerosis. LDL oxidation plays a central role].

PMID- 7564615
TI  - [Break in the trend of treatment of acute poisoning. Ventricular lavage may be
      substituted by active carbon].

PMID- 7564617
TI  - [Arterial surgery of the extremities without angiography. A simpler preoperative
      survey with color doppler].

PMID- 7564618
TI  - [Lactose intolerance after gastroenteritis. Not the serious clinical problem as
      supposed earlier].

PMID- 7564619
TI  - [P-pill research is kept on low heat. Yet there is a vaccine out of reach so
      far].

PMID- 7564620
TI  - [Serious cases of allergy caused by wrongly labeled food. Information and
      education minimize the risks].

PMID- 7564621
TI  - [Peroral selenium therapy in growth pain in children].

PMID- 7564622
TI  - [Legal protection of patient status. A way to strengthen the patient's right to
      health care?].

PMID- 7564623
TI  - [Abuse of statistics in the treatment with ginseng].

PMID- 7564624
TI  - [No convincing results in the use of ginseng preparations].

PMID- 7564625
TI  - [How to prevent mistakes].

PMID- 7564626
TI  - [Information about adverse effects of drugs is not included in Fass (Swedish drug
      catalog)].

PMID- 7564627
TI  - [Combine the vaccination against influenza and pneumococcal infections. Great
      benefits for the elderly].

PMID- 7564628
TI  - [A caution for psilocybine in wild mushrooms. A young addict acquired acute
      delirium].

PMID- 7564629
TI  - [Pneumococcal vaccine for children prior the year of 2000. Promising data on
      vaccine candidates].

PMID- 7564631
TI  - [Tularemia occurs in the whole country. A good year for rodents prepares the
      ground for an epidemic].

PMID- 7564630
TI  - [The next influenza wave is a question of time. A new variant may cause a
      pandemic].

PMID- 7564632
TI  - [A rapid troponin T test in acute chest pain. Evaluation in the routine clinical
      work].

PMID- 7564633
TI  - [Relentless fight against malaria in Thailand].

PMID- 7564634
TI  - [Towards a new drug management].

PMID- 7564635
TI  - [Drug utilization should be analyzed on the premises].

PMID- 7564637
TI  - [A traveller to the East is more exposed to the risk of infection].

PMID- 7564636
TI  - [A debate on test-tube fertilization. Conclusions by the medical-ethical
      committee should not be surprising!].

PMID- 7564638
TI  - [Evaluation of the FINSAM at SoS and RFV: importance of finding ways of
      cooperation between health care and social insurance].

PMID- 7564639
TI  - [A test for a new diploma for competence in clinical trial management].

PMID- 7564640
TI  - [At what age is estrogen therapy beneficial?].

PMID- 7564641
TI  - [2 hours--too careful return to work].

PMID- 7564642
TI  - [Routine cystoscopy after Burch cystoplasty in incontinence?].

PMID- 7564643
TI  - [Need for serious debate on remedial and dyslexia-classes].

PMID- 7564644
TI  - [Estrogen and thrombosis--additional research still needed].

PMID- 7564645
TI  - [We certainly can afford good health services for all!].

PMID- 7564646
TI  - [Decoction of rice as a cure for diarrhea. An old-fashioned treatment in a new
      light].

PMID- 7564647
TI  - [Let us not forget children of the mentally ill!].

PMID- 7564648
TI  - [Children of mentally ill parents must get more support].

PMID- 7564649
TI  - [Future drugs against aging? New research on molecular background of aging].

PMID- 7564650
TI  - [Inflammatory bowel disease or infectious colitis? Clinical picture, microbiology
      and histology offer guidelines].

PMID- 7564651
TI  - [Many problems in the diagnosis of colitis. 2 case reports].

PMID- 7564653
TI  - [Better instruction at the obstetrics departments].

PMID- 7564654
TI  - [Young children may suffer from bacterial gastritis].

PMID- 7564652
TI  - [Is depression in men under-treated? High frequency of sudden, unexpected
      suicides].

PMID- 7564655
TI  - [Subdural hematoma after spinal anesthesia. A rare but serious complication].

PMID- 7564656
TI  - [Does restricted housing space protect against allergy? Hypotheses on low
      frequency of allergies in Eastern Europe].

PMID- 7564658
TI  - [Fever and shivering during dobutamine infusions].

PMID- 7564657
TI  - [Intensive studies on Drosophila lead to Nobel prize. A few genes direct the
      development of parts of the body].

PMID- 7564659
TI  - [Pulmonary edema after Narcanti].

PMID- 7564660
TI  - [Bronchospasm and cough connected to Losartan].

PMID- 7564662
TI  - [Muscular symptoms during fluoroquinolone treatment may be adverse effects].

PMID- 7564661
TI  - [ACE inhibitors may cause hypoglycemia in patients with diabetes].

PMID- 7564663
TI  - Trading trust for blood money.

PMID- 7564664
TI  - Paraoxonase: another factor in NIDDM cardiovascular disease.

PMID- 7564665
TI  - Autologous bone-marrow transplantation in childhood acute lymphoblastic
      leukaemia.

PMID- 7564666
TI  - Lessons from a very hot summer.

PMID- 7564667
TI  - Towards even fewer colostomies....

PMID- 7564668
TI  - Environmental medicine for all: getting there form here.

PMID- 7564669
TI  - Dopaminergic defect of enteric nervous system in Parkinson's disease patients
      with chronic constipation.
AB  - Clinical studies suggest that gut disorders are common in Parkinson's disease,
      but the morphological basis is unknown. Depletion of dopamine-containing neurons
      in the central nervous system is a basic defect in Parkinson's disease. We
      compared colonic tissue from 11 patients with advanced Parkinson's disease, 17
      with adenocarcinoma (normal tissue was studied), and five who underwent colectomy
      for severe constipation. Immunohistochemistry was used to stain myenteric and
      submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal
      polypeptide (VIP). Each class of neurons was quantified as a percentage of the
      total neuronal population stained for the marker protein gene product 9.5. Nine
      of the 11 Parkinson's disease patients had substantially fewer dopaminergic
      myenteric neurons than the other subjects (mean 0.4 [SE 0.2] vs 6.9 [2.3] in
      controls and 5.7 [2.0] in constipated subjects). There was very little difference
      between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two
      Parkinson's disease patients had similar distributions of all types of neurons,
      including dopaminergic myenteric neurons, to the controls. High-performance
      liquid chromatography showed lower levels of dopamine in the muscularis externa
      (but not mucosa) in four Parkinson's disease patients than in four controls (7.3
      [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopamine metabolites were
      similar in the two groups. The identification of this defect of dopaminergic
      neurons in the enteric nervous system in Parkinson's disease may lead to better
      treatment of colorectal dysfunction in this disease.

PMID- 7564670
TI  - Early administration of terlipressin plus glyceryl trinitrate to control active
      upper gastrointestinal bleeding in cirrhotic patients.
AB  - Upper gastrointestinal bleeding (GIB) is a major complication in cirrhotic
      patients. Endoscopy and oesophageal sclerosis are reference treatments and must
      be done as soon as possible. However, such treatment is not possible unless the
      patient is admitted to hospital. In a prospective, randomised, double-blind
      trial, we compared the efficacy of terlipressin combined with glyceryl trinitrate
      (TER-GTN), administered as early as possible to 76 patients with cirrhosis who
      had active GIB (84 bleeding episodes). Infusion was done at the patient's home by
      the physician on the emergency team (a mobile intensive care unit) if the patient
      had GIB and a history and clinical signs of cirrhosis. Patients received either
      an intravenous injection (1 to 2 mg) of TER-GTN or a double-placebo injection,
      and then another injection at 4 and 8 h. Control of bleeding, rebleeding, and
      mortality rate at days 15 and 42 were evaluated. In most patients, endoscopy
      confirmed the rupture of oesophageal varices (75.7%). Bleeding control was
      significantly better in the TER-GTN group (n = 41) than in the double-placebo
      group (n = 43) (p = 0.034). Mortality due to bleeding episodes was significantly
      lower in the TER-GTN group than in the double-placebo group at day 15 (p = 0.035)
      and at day 42 (p = 0.06). There were no serious side-effects. Early
      administration of TER-GTN lowers the deleterious consequences of prolonged
      hypovolaemia on the hepatic function of these patients.

PMID- 7564671
TI  - Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2
      diabetes.
AB  - Paraoxonase is a high-density-lipoprotein-associated enzyme capable of
      hydrolysing lipid peroxides. Thus it might protect lipoproteins from oxidation.
      It has two isoforms, which arise from a glutamine (A isoform) to arginine (B
      isoform) interchange at position 192. The relevance of this polymorphism to
      coronary heart disease (CHD) in non-insulin-dependent diabetic patients was
      investigated in case-control study. Of the 434 patients, 171 had confirmed
      coronary artery disease; the other 263 had no history of such disease. The B
      allele and AB+BB genotypes were associated with an increased risk of coronary
      heart disease. Compared with subjects homozygous for the A allele (AA genotype),
      the odds ratio of CHD for subjects homozygous for the B allele was 2.5 (95% CI
      1.2-5.3) and that for those heterozygous for the B allele was 1.6 (95% CI 1.1
      2.4), suggesting a codominant effect on cardiovascular risk. When subjected to
      multivariate analysis, the B allele remained significantly associated with CHD
      (odds ratio 1.94, p = 0.03). The paraoxonase gene polymorphism is thus an
      independent cardiovascular risk factor in non-insulin-dependent diabetic
      patients. A possible explanation for this finding is that activity of the
      paraoxonase B isotype does not protect well against lipid oxidation, a major
      atherogenic pathway.

PMID- 7564673
TI  - Hypokalaemia related to acute chloroquine ingestion.
AB  - Large doses of chloroquine can cause poisoning. Our aim was to determine the
      possible relation between the plasma potassium concentration on admission with
      the severity of acute chloroquine poisoning and to assess the mechanism of
      chloroquine-induced hypokalaemia. We conducted a retrospective study of 191
      consecutive cases. The main data included the occurrence of vomiting before
      admission, plasma, and urinary potassium concentration at admission, whole blood
      chloroquine concentration on admission, haemodynamic parameters and ECG,
      administration of catecholamines and outcome. Mean blood chloroquine level was
      20.1 mumol/L (SD 14.3) (therapeutic level < or = 6 mumol/L). Mean plasma
      potassium concentration was 3.0 mmol/L (0.8) and was lower in the subjects who
      died than in those who survived (p = 0.0003). Plasma potassium varied directly
      with the systolic blood pressure and inversely with the QRS and QT. Plasma
      potassium varied inversely with the blood chloroquine (p = 0.0001; tau = -0.42).
      Acute chloroquine intoxication is responsible for a hypokalaemia which correlates
      with the gravity of the intoxication and may be due to a transport-dependent
      mechanism. Plasma potassium concentrations should be carefully observed,
      particularly among patients who also receive catecholamine infusions. We should
      keep in mind, however, that overzealous repletion invokes the risk of subsequent
      hyperkalaemia and thus should be avoided.

PMID- 7564672
TI  - Autologous bone-marrow transplants compared with chemotherapy for children with
      acute lymphoblastic leukaemia in a second remission: a matched-pair analysis. The
      Berlin-Frankfurt-Munster Study Group.
AB  - It is unclear how best to treat children with acute lymphoblastic leukaemia (ALL)
      who are in a second remission. Treatment with bone-marrow transplants from HLA
      identical siblings results in a statistically greater likelihood of leukaemia
      free survival than does chemotherapy. Less than 25% of relapsed patients are able
      to benefit from this therapy due to a lack of matching donors; chemoradiotherapy
      or autologous BMT are considered for the rest. We compared treatment results for
      children who underwent autologous BMT with those who had chemotherapy. All
      patients were registered between 1983-94 in the multicentre trials. We selected
      groups of patients by matching variables associated with treatment outcome and
      duration of second remission. 52 matched-pairs were studied. The probability of
      event-free survival at 9 years was 0.32 (SD 0.07) for patients receiving
      chemotherapy versus 0.26 (SD 0.07) for patients who underwent autologous BMT. For
      two groups--children with prognostic factors indicating high risk of relapse and
      those with factors indicating lower risk--the outcome from transplantation did
      not differ significantly from that of chemotherapy: no advantage of autologous
      BMT over chemotherapy as post-induction treatment for children with ALL in a
      second remission could be detected with regard to event-free survival. Because
      autologous BMT has been used as the final step of treatment it is possible that
      its relative ineffectiveness has been due to the lack of continuation therapy
      after transplant. Attempts should be made to complement autologous BMT by
      subsequent immunotherapy, molecular biotherapy, chemotherapy, or a combination of
      these.

PMID- 7564676
TI  - Can low-back pain be due to lumbar-artery disease?

PMID- 7564675
TI  - Breast cancer: cause and prevention.

PMID- 7564674
TI  - Effects of azithromycin on malariometric indices in The Gambia.
AB  - Azithromycin (a macrolide-like antibiotic) has antimalarial effects in vitro and
      in animal models. In the course of a randomised trial of trachoma control we
      examined the effects of azithromycin on parasite and spleen rates in the
      population aged 5-14 years from eight villages in the Farafenni study area in The
      Gambia, West Africa. The entire population of four treatment villages received
      three doses of azithromycin 20 mg/kg weekly (days 1, 8, and 15) and four control
      villages received daily tetracycline eye ointment topically (days 1-42). Among
      226 children studied before treatment and at day 28, azithromycin reduced the
      proportions with Plasmodium falciparum parasites (rate ratio 0.56, 95% confidence
      interval 0.44-0.71; p < 0.0001), with palpable spleens (RR 0.50, 95% CI 0.36
      0.70; p < 0.0001), with febrile parasitaemia (RR 0.45, 95% CI 0.27-0.75; p <
      0.01), and with P malariae infection (p < 0.001). This effect was related more to
      resolution of parasitaemia than to prevention of new infections.

PMID- 7564677
TI  - What kind of crisis is the NHS in?

PMID- 7564678
TI  - Combination superior to zidovudine in Delta trial.

PMID- 7564680
TI  - Support for needle-exchange programmes.

PMID- 7564679
TI  - Oral ganciclovir fails to prevent CMV in HIV trial.

PMID- 7564681
TI  - Creutzfeldt-Jakob disease in a dairy farmer.

PMID- 7564682
TI  - Creutzfeldt-Jakob disease in Europe.

PMID- 7564683
TI  - Pott's paraplegia today.

PMID- 7564684
TI  - Dual-energy X-ray absorptiometry results differ between machines.

PMID- 7564685
TI  - Vesico-ureteric reflux, urinary-tract infection, and renal damage in children.

PMID- 7564686
TI  - Vesico-ureteric reflux, urinary-tract infection, and renal damage in children.

PMID- 7564688
TI  - Evidence-based in-vitro fertilisation.

PMID- 7564687
TI  - Hepatitis B vaccination strategy for newborn babies.

PMID- 7564689
TI  - Pasteurella "SP" group infection after a guinea pig bite.

PMID- 7564690
TI  - Long-term hospital support for dialysis.

PMID- 7564692
TI  - Pathologist or laboratory physician?

PMID- 7564691
TI  - Occupational allergy to propacetamol.

PMID- 7564693
TI  - Role of lymphagenesis in neovascularisation.

PMID- 7564694
TI  - Pathologist or laboratory physician.

PMID- 7564695
TI  - Pathologist or laboratory physician.

PMID- 7564696
TI  - Standardised mortality ratios.

PMID- 7564697
TI  - Burkholderia pseudomallei and Indian plague-like illness.

PMID- 7564698
TI  - Bone mineral loss and recovery after cardiac transplantation.

PMID- 7564699
TI  - Impact factor as a misleading tool in evaluation of medical journals.

PMID- 7564700
TI  - Will the real Dr Doublit please stand up?

PMID- 7564701
TI  - Community participation in health care.

PMID- 7564702
TI  - Do refugees belong in camps?

PMID- 7564703
TI  - Neonatal blood tests to exclude caesarean section as a cause of maternal-fetal
      transmission of hepatitis C.

PMID- 7564704
TI  - Genetic variation of the 5-HT2A receptor and response to clozapine.

PMID- 7564706
TI  - Effects of compassionate care on the homeless.

PMID- 7564705
TI  - Genetic variation of the 5-HT2A receptor and response to clozapine.

PMID- 7564707
TI  - Successful autotransplantation of lingual thyroid: 37-year follow-up.

PMID- 7564708
TI  - Clinical staging system for AIDS patients.

PMID- 7564709
TI  - Programmed cell death in brains of HIV-1-positive pre-AIDS patients.

PMID- 7564710
TI  - New chlamydial antigen as a serological marker in HIV infection.

PMID- 7564711
TI  - Genetic diversity and HIV detection by polymerase chain reaction.

PMID- 7564712
TI  - Epstein-Barr virus and autoimmune hepatitis.

PMID- 7564713
TI  - Remission of epilepsy.

PMID- 7564714
TI  - Family infection with methicillin-resistant Staphylococcus aureus.

PMID- 7564715
TI  - Are varicella zoster and herpes simplex sentinel lesions for cytomegalovirus in
      renal transplant recipients?

PMID- 7564716
TI  - Melanoma and sun exposure.

PMID- 7564718
TI  - The diagnosis I longed to make.

PMID- 7564717
TI  - Untreated coeliac disease and attempted suicide.

PMID- 7564719
TI  - Trumping the ACE.

PMID- 7564720
TI  - Buying into the orphan drug market.

PMID- 7564721
TI  - Taming the brain storms: felbamate updated.

PMID- 7564723
TI  - How to treat bacteraemic Mycobacterium avium complex disease.

PMID- 7564722
TI  - Multiple subcortical infarction: CADASIL in context. Cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leucoencephalopathy.

PMID- 7564724
TI  - Umbilical cord-blood transplantation: is there a future?

PMID- 7564725
TI  - The effectiveness of combined oral lysine acetylsalicylate and metoclopramide
      compared with oral sumatriptan for migraine.
AB  - Aspirin is commonly used to treat migraine attacks, although sumatriptan, a much
      more expensive treatment, is also effective. We compared a combination of lysine
      acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide
      (LAS+MTC) with oral sumatriptan (100 mg) and placebo in 421 patients with
      migraine. LAS+MTC was as effective as sumatriptan with a decrease of headache
      from severe or moderate to mild or none of 57% and 53%, respectively, for the
      first migraine attack treated. Both treatments were better than placebo (success
      rate 24%, p < 0.0001). LAS+MTC was significantly more effective in the treatment
      of nausea than sumatriptan (p < 0.0001) and was better tolerated (adverse events
      in 18% and 28%, respectively, p < 0.05). LAS+MTC is as effective as sumatriptan
      in the treatment of migraine attacks. It is also much cheaper.

PMID- 7564726
TI  - A prospective study of antineutrophil cytoplasmic antibody (c-ANCA) and clinical
      criteria in diagnosing Wegener's granulomatosis.
AB  - Antineutrophil cytoplasmic antibody (c-ANCA) has a reported sensitivity and
      specificity greater than 90% for active Wegener's granulomatosis in selected
      patients with previously-defined disease. Because of these reports, some
      clinicians believe that a positive c-ANCA result provides strong circumstantial
      evidence for the diagnosis of Wegener's granulomatosis in patients with
      compatible clinical symptoms. However, this approach has not been examined
      prospectively. We prospectively studied 346 consecutive patients suspected of
      having vasculitis; those with previously established Wegener's granulomatosis (n
      = 29) or receiving immunosuppressives other than corticosteroids (n = 65) at
      baseline were excluded. Measures included a baseline c-ANCA, blinded chart
      reviews to record symptoms, physical findings, and corticosteroid use at
      baseline, and 2 to 8 months later to record final diagnoses and biopsy results.
      Wegener's granulomatosis was defined using the 1990 American College of
      Rheumatology (ACR) criteria, which does not require a biopsy. Follow-up
      information was available for 212 (84%) of the 252 patients eligible for this
      study (no corticosteroids: n = 174; corticosteroids: n = 78). 25 patients with
      compatible symptoms were classified with Wegener's granulomatosis by ACR
      criteria; only 6 of the 25 had biopsy-proven disease. 14 of these 212 patients
      had positive c-ANCA results. The overall sensitivity and specificity of c-ANCA
      for ACR-defined Wegener's granulomatosis were 28% (95% CI, 10%-46%) and 96% (93%
      99%) respectively. The positive and negative predictive values were 0.50 and
      0.91. The specificity remained greater than 90% regardless of baseline
      corticosteroid use or disease activity; however, the sensitivity and positive
      predictive value remained poor. For Wegener's granulomatosis defined by biopsy
      criteria and compatible clinical symptoms, the sensitivity was 83% (53%-100%);
      however, the positive predictive value was 36%. These results raise serious
      questions about the use of positive c-ANCA tests in diagnosing Wegener's
      granulomatosis in patients with clinical symptoms alone.

PMID- 7564727
TI  - Is senile dementia "age-related" or "ageing-related"?--evidence from meta
      analysis of dementia prevalence in the oldest old.
AB  - The observation of an exponential increase in senile dementia prevalence with age
      has led to the conclusion that this disease may be inevitable in those who live
      long enough. The alternative view is that at very high ages the prevalence rate
      levels off. Studies conducted to date have not included sufficient numbers of
      very old people to resolve this difference of opinion. The question is important
      both to our understanding of the biological mechanisms involved and for public
      health planning. We have carried out a meta-analysis of nine epidemiological
      studies of senile dementia that used DSM III diagnostic criteria and that
      included samples of elderly people over age 80. The resulting curve was best
      described as a flattened S curve that fitted a modified logistic function rather
      than an exponential pattern. The rate of increase in senile dementia prevalence
      was found to fall in the age range 80-84, and at around the age of 95 prevalence
      was seen to level off to about 40%. It seems that senile dementia is better
      conceptualised as an "age-related" (ie, occurring within a specific age range)
      rather than as an "ageing-related" disorder (that is, caused by the ageing
      process itself). Very elderly survivors may be at diminishing risk of dementia
      and this has implications for public health policy.

PMID- 7564728
TI  - Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited arterial disease of the brain
      recently mapped to chromosome 19. We studied 148 subjects belonging to seven
      families by magnetic resonance imaging and genetic linkage analysis. 45 family
      members (23 males and 22 females) were clinically affected. Frequent signs were
      recurrent subcortical ischaemic events (84%), progressive or stepwise subcortical
      dementia with pseudobulbar palsy (31%), migraine with aura (22%), and mood
      disorders with severe depressive episodes (20%). All symptomatic subjects had
      prominent signal abnormalities on MRI with hyperintense lesions on T2-weighted
      images in the subcortical white-matter and basal ganglia which were also present
      in 19 asymptomatic subjects. The age at onset of symptoms was mean 45 (SD [10-6])
      years, with attacks of migraine with aura occurring earlier in life (38.1 [8.03]
      years) than ischaemic events (49.3 [10.7] years). The mean age at death was 64.5
      (10.6) years. On the basis of MRI data, the penetrance of the disease appears
      complete between 30 and 40 years of age. Genetic analysis showed strong linkage
      to the CADASIL locus for all seven families, suggesting genetic homogeneity.
      CADASIL is a hereditary cause of stroke, migraine with aura, mood disorders and
      dementia. The diagnosis should be considered not only in patients with recurrent
      small subcortical infarcts leading to dementia, but also in patients with
      transient ischaemic attacks, migraine with aura or severe mood disturbances,
      whenever MRI reveals prominent signal abnormalities in the subcortical white
      matter and basal ganglia. Clinical and MRI investigations of family members are
      then crucial for the diagnosis which can be confirmed by genetic linkage
      analysis. The disease is probably largely undiagnosed.

PMID- 7564729
TI  - Genotyping of hepatitis D virus by restriction-fragment length polymorphism and
      relation to outcome of hepatitis D.
AB  - The outcome of hepatitis D virus (HDV) superinfection varies among patients and
      in different geographical areas. To find out whether HDV genotype affects
      outcome, we used a simple genotyping method based on restriction-fragment length
      polymorphism with enzymes XhoI and SacII for cleavage of PCR products of the HDV
      genome. Of samples from 88 patients studied, the genotypes of 61 were confirmed
      by two methods--analysis with both enzymes or by combined restriction-enzyme and
      direct sequencing analyses--with consistent results. No genotype III HDV was
      detected among these patients. The majority of patients with acute HDV infection
      (35/41 [85%]) had genotype II HDV. Among the 41 patients with acute infection,
      four of six with genotype I had fulminant disease compared with two of 35 with
      genotype II. Among patients in chronic stage, cirrhosis or hepatocellular
      carcinoma were found in 12 of 18 with genotype I HDV and eight of 29 with
      genotype II. Thus genotype II was the predominant HDV genotype in this study in
      Taiwan. Genotype II HDV was less frequently associated with fulminant hepatitis
      at the acute stage or with an unfavourable long-term clinical outcome at the
      chronic stage than was genotype I.

PMID- 7564730
TI  - Increased frequency of homozygosity of abnormal mannan-binding-protein alleles in
      patients with suspected immunodeficiency.
AB  - A low plasma concentration of mannan-binding protein (MBP) impairs opsonisation
      and phagocytosis. Three different mutations in the MBP gene have a dominant
      effect on MBP concentration. We investigated the frequency of the abnormal MBP
      alleles in 228 unrelated patients suspected of various non-HIV-related
      immunodeficiencies. The frequency of heterozygotes for the abnormal alleles was
      not different from that in the background population (36.0% and 37.4%,
      respectively). By contrast, the frequency of homozygotes for the abnormal alleles
      was significantly increased (8.3% and 0.8%, respectively; p = 0.0017). This
      finding implies that homozygotes for abnormal MBP alleles are predisposed to
      recurrent infections.

PMID- 7564731
TI  - Activated-guidewire technique for treating chronic coronary artery occlusion.
AB  - Coronary angioplasty was successfully carried out with an activated guidewire
      technique in 33 of 47 patients who had undergone a failed attempt at conventional
      angioplasty for the treatment of chronic coronary artery occlusion. 80% of these
      occlusions were stump-like occlusions. This technique involves the attachment of
      a hand-held battery-driven motorised device to standard angioplasty equipment and
      can be used at any time during the procedure. The device generates complex
      vibratory movement in the guidewire to facilitate crossing of occluded vessels.

PMID- 7564732
TI  - Necropsy as a research method in the age of molecular pathology.

PMID- 7564733
TI  - Tuberculosis in prisons--forgotten plague.

PMID- 7564734
TI  - Pathophysiology of carotid sinus hypersensitivity in elderly patients.
AB  - Carotid sinus hypersensitivity (CSH) is recognised in up to 45% of elderly
      patients with syncope, falls, and dizziness that may not be attributed to
      specific myocardial sinus node dysfunction, various diseases that affect
      pacemaker activity, cardiac output and blood supply to the brain. The
      pathophysiology of CSH is unclear but it is associated with ageing, hypertension,
      and ischaemic heart disease. CSH is potentially treatable with dual chamber
      pacing for prolonged sinus arrest (cardio-inhibitory CSH) but therapy for the
      more prevalent hypotension (vasodepressor CSH) is unsatisfactory. However,
      hypersensitivity of the carotid sinus is not consistent with the known blunting
      effects of senescence and hypertension on baroreflex sensitivity. The present
      hypothesis proposes that CSH in elderly patients results from up-regulation of
      brainstem postsynaptic alpha-2 adrenoceptors. Reduced carotid sinus compliance in
      elderly arteriosclerotic hypertensive patients will reduce afferent impulse
      traffic in the baroreflex pathway. Such relative deafferentation may be expected
      to cause baroreflex postsynaptic hypersensitivity, mediated by up-regulation of
      the dominant postsynaptic receptor population in the baroreflex pathway, ie,
      alpha-2 adrenoceptors. Vigorous carotid sinus stimulation, eg, massage, could
      thus cause an overshoot baroreflex efferent response, resulting in profound
      hypotension and bradycardia. Hypotension and bradycardia are compounded by the
      effects of age, hypertension, ischaemic heart disease and arteriosclerosis on
      rapid cardiovascular compensation, resulting in cerebral hypoperfusion and
      syncope. Thus CSH in elderly patients should be considered as a clinical marker
      of widespread arteriosclerotic disease, rather than as a distinct disease entity.
      If correct, this hypothesis has potentially important implications for the
      pharmacotherapy of hypotension-related symptoms in elderly arteriosclerotic
      patients.

PMID- 7564735
TI  - The war on the war on poverty.

PMID- 7564736
TI  - HIV gene arrests cell cycle.

PMID- 7564737
TI  - Risks and benefits of calcium antagonists.

PMID- 7564738
TI  - Risks and benefits of calcium antagonists.

PMID- 7564739
TI  - Risks and benefits of calcium antagonists.

PMID- 7564740
TI  - Risks and benefits of calcium antagonists.

PMID- 7564741
TI  - Risks and benefits of calcium antagonists.

PMID- 7564742
TI  - Condom semen samples for unlinked anonymous HIV testing.

PMID- 7564743
TI  - 9-year-old child with falling CD4 count after neonatal HIV.

PMID- 7564744
TI  - Transmission of hepatitis B virus by HBV-negative blood transfusion.

PMID- 7564745
TI  - Skin cancer in transplant recipients.

PMID- 7564746
TI  - Skin cancer in transplant recipients.

PMID- 7564747
TI  - Why do cystic duct clips migrate into the common bile duct?

PMID- 7564748
TI  - Type I diabetes and pregnancy.

PMID- 7564749
TI  - IgM-specific measles-virus antibody in families with a high frequency of Crohn's
      disease.

PMID- 7564750
TI  - Apolipoprotein E-epsilon 4 gene dose.

PMID- 7564751
TI  - Bronchodilation subsensitivity to salbutamol after salmeterol.

PMID- 7564752
TI  - Bronchodilation subsensitivity to salbutamol after salmeterol.

PMID- 7564753
TI  - Bronchodilation subsensitivity to salbutamol after salmeterol.

PMID- 7564754
TI  - 5HT2A receptor gene and bipolar affective disorder.

PMID- 7564755
TI  - Priorities in humanitarian relief.

PMID- 7564757
TI  - Attitudes of Japanese physicians towards life-sustaining treatment.

PMID- 7564756
TI  - Attitudes of Japanese physicians towards life-sustaining treatment.

PMID- 7564758
TI  - Injury research and the US gun lobby.

PMID- 7564759
TI  - Rifampicin-resistant tuberculosis.

PMID- 7564760
TI  - Antibiotics, free radicals, and acute pancreatitis.

PMID- 7564761
TI  - Remission of leukaemic meningitis after fludarabine.

PMID- 7564762
TI  - Requesting vitamin B12 and folate assays.

PMID- 7564763
TI  - Requesting vitamin B12 and folate assays.

PMID- 7564764
TI  - Requesting vitamin B12 and folate assays.

PMID- 7564765
TI  - Spurious rises in troponin T in end-stage renal disease.

PMID- 7564766
TI  - White cell enhancement in the treatment of severe candidosis.

PMID- 7564767
TI  - Burkholderia pseudomallei and Indian plague-like illness.

PMID- 7564768
TI  - Topical treatment with dinitrochlorobenzene.

PMID- 7564769
TI  - Megatrials and management of acute myocardial infarction.

PMID- 7564770
TI  - Molecular typing as an epidemiological tool in the study of sexual networks.

PMID- 7564771
TI  - Ciprofloxacin-associated Clostridium difficile disease.

PMID- 7564772
TI  - Methicillin-resistant Staphylococcus aureus in the community.

PMID- 7564773
TI  - Mortality from cardiac arrest.

PMID- 7564774
TI  - Interleukin-1 receptor antagonist gene polymorphism and multiple sclerosis.

PMID- 7564775
TI  - Mortality from cardiac arrest.

PMID- 7564777
TI  - English as she is wrote.

PMID- 7564776
TI  - History of informed medical consent.

PMID- 7564778
TI  - SAPping maternal health.

PMID- 7564779
TI  - Prognostic value of portal haemodynamics.

PMID- 7564780
TI  - Understanding "informed consent".

PMID- 7564781
TI  - False memory syndrome.

PMID- 7564782
TI  - Tackling liver cancer with interferon.

PMID- 7564783
TI  - From "black box" to bedside, one day.

PMID- 7564784
TI  - Randomised trial of effects of interferon-alpha on incidence of hepatocellular
      carcinoma in chronic active hepatitis C with cirrhosis.
AB  - Patients with chronic active hepatitis C and cirrhosis often develop
      hepatocellular carcinoma. Interferon (IFN) seems to be effective in some patients
      but whether it prevents carcinogenesis is unknown. In a prospective randomised
      controlled trial, we evaluated the effects of IFN-alpha in cirrhotic patients
      with HCV infection because of their high risk of hepatocellular carcinoma. 90
      patients with compensated chronic active hepatitis C with cirrhosis were randomly
      allocated to receive IFN-alpha (6 MU three times weekly for 12-24 weeks) (45
      patients) or symptomatic treatment (45 controls), and were followed up for 2-7
      years. In nine controls, alanine aminotransferase (ALT) decreased to less than 80
      IU/L but did not stay in the normal range. In 19 patients given IFN-alpha, ALT
      decreased to less than 80 IU/L (in seven patients, it became and stayed normal; p
      = 0.011, Wilcoxon rank-sum test). However, the mean change in ALT was not
      significantly different between the two groups. The mean change in peak alpha
      fetoprotein values was smaller in patients given IFN-alpha than in controls (p =
      0.021). The mean change in the serum albumin level was higher in the IFN-alpha
      group (p < 0.001). The histological activity index in the 12 IFN-alpha patients
      undergoing a second biopsy after therapy was improved (p = 0.031). Hepatitis C
      viral RNA disappeared in seven (16%) of the 45 IFN-alpha patients (95% CI, 7-29%)
      and in none of the 45 controls (0-8%; p = 0.018). Hepatocellular carcinoma was
      detected in two (4%, 1-15%) IFN-alpha patients and 17 (38%, 24-54%) controls (p =
      0.002, Wilcoxon signed-rank test). The risk ratio of IFN-alpha treatment versus
      symptomatic treatment was 0.067 (0.009-0.530; p = 0.010 Cox's proportional
      hazards). IFN-alpha improved liver function in chronic active hepatitis C with
      cirrhosis, and its use was associated with a decreased incidence of
      hepatocellular carcinoma.

PMID- 7564785
TI  - Relation between portal pressure response to pharmacotherapy and risk of
      recurrent variceal haemorrhage in patients with cirrhosis.
AB  - In patients with variceal bleeding as a complication of hepatic cirrhosis,
      propranolol therapy reduces the risk of recurrent variceal haemorrhage. However,
      the relation between portal pressure response to pharmacological treatment and
      clinical events has not been well defined. This relation was prospectively
      investigated in 69 cirrhotic patients receiving continued propranolol therapy
      after an episode of variceal bleeding. Hepatic venous pressure gradient (HVPG)
      was measured before and at 3 months of continued drug therapy. At 3 months HVPG
      had fallen by 20% or more in 25 patients. During follow-up of 28 (SD 17) months
      rebleeding occurred in 2 of these 25 patients compared with 23 of 44 who had
      lesser reductions in HVPG. Cumulative probability of rebleeding at 1, 2, and 3
      years was 4%, 9%, and 9% in patients with a decrease in HVPG > or = 20%, and 28%,
      39%, and 66% in patients with a decrease in HVPG < 20% (p < 0.001, log-rank
      test). On multivariate analysis, a decrease in HVPG > or = 20% was the only
      independent predictor of rebleeding (relative risk 0.09, 95% CI 0.02-0.41. Of the
      8 patients in whom the HVPG fell to 12 mm Hg or less, none rebled. This study
      suggests that measurement of the HVPG response to pharmacotherapy will provide
      useful prognostic information on the long-term risk of variceal rebleeding.

PMID- 7564786
TI  - Informed versus randomised consent to clinical trials.
AB  - We compared different procedures for seeking consent to participate in a sham
      randomised clinical trial and assessed whether refusal is affected by awareness
      of the severity of outlook. 2035 healthy subjects aged between 20 and 80 years,
      who visited a scientific exhibition, were enrolled in a hypothetical trial of
      experimental versus standard therapy, and randomly assigned to groups asked for
      conventional informed consent or prerandomisation consent. There were four study
      groups: one-sided informed consent for randomisation (subjects who refused would
      receive standard treatment); two-sided informed consent for randomisation
      (subjects who refused could choose between standard and experimental treatment);
      randomised consent to experimental treatment (subjects who refused would receive
      standard treatment); and randomised consent to standard treatment (subjects who
      refused would receive experimental treatment). The refusal rates were 16.2%,
      19.9%, 12.1%, and 49.2%, respectively. The perceived severity of the simulated
      disease affected the refusal rate: the worse the outlook, the lower the refusal
      rate for informed consent or for consent after randomisation to new treatment,
      and the higher the refusal rate for consent after randomisation to standard
      treatment. The prerandomisation design seems to be efficient in a one-sided
      clinical scenario (eg, a trial of a new drug that would not be given outside the
      trial) because the refusal rate was substantially lower for prerandomisation to
      the new treatment than for conventional one-sided informed consent. However, in a
      two-sided clinical scenario (eg, a trial comparing similar treatments) the
      prerandomisation design is potentially highly inefficient; the refusal rate was
      much higher for prerandomisation to standard treatment than for conventional two
      sided informed consent.

PMID- 7564787
TI  - Breastfeeding as prophylaxis against atopic disease: prospective follow-up study
      until 17 years old.
AB  - Atopic diseases constitute a common health problem. For infants at hereditary
      risk, prophylaxis of atopy has been sought in elimination diets and other
      preventive measures. We followed up healthy infants during their first year, and
      then at ages 1, 3, 5, 10, and 17 years to determine the effect on atopic disease
      of breastfeeding. Of the initial 236 infants, 150 completed the follow-up, which
      included history taking, physical examination, and laboratory tests for allergy.
      The subjects were divided into three groups: prolonged (> 6 months), intermediate
      (1-6 months), and short or no (< 1 month) breastfeeding. The prevalence of
      manifest atopy throughout follow-up was highest in the group who had little or no
      breastfeeding (p < 0.05, analysis of variance and covariance with repeated
      measures [ANOVA]). Prevalence of eczema at ages 1 and 3 years was lowest (p =
      0.03, ANOVA) in the prolonged breastfeeding group, prevalence of food allergy was
      highest in the little or no groups (p = 0.02, ANOVA) at 1-3 years, and
      respiratory allergy was also most prevalent in the latter group (p = 0.01, ANOVA)
      having risen to 65% at 17 years of age. Prevalences in the prolonged,
      intermediate, and little or no groups at age 17 were 42 (95% CI 31-52)%, 36 (28
      44)%, and 65 (56-74)% (p = 0.02, trend test) for atopy, respectively, and 8 (6
      10)%, 23 (21-25)%, and 54 (52-56)% (p = 0.0001, trend test) for substantial
      atopy. We conclude that breastfeeding is prophylactic against atopic disease-
      including atopic eczema, food allergy, and respiratory allergy--throughout
      childhood and adolescence.

PMID- 7564788
TI  - Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida.
AB  - Periconceptional folate supplementation reduces the risk of neural-tube defects.
      We studied the frequency of the 677C-->T mutation in the 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene in 55 patients with spina bifida
      and parents of such patients (70 mothers, 60 fathers). 5% of 207 controls were
      homozygous for the 677C-->T mutation compared with 16% of mothers, 10% of
      fathers, and 13% of patients. The mutation was associated with decreased MTHFR
      activity, low plasma folate, and high plasma homocysteine and red-cell folate
      concentrations. The 677C-->T mutation should be regarded as a genetic risk factor
      for spina bifida.

PMID- 7564789
TI  - Role of thrombin in pulmonary fibrosis.
AB  - Pulmonary fibrosis commonly develops in systemic sclerosis. We assessed the role
      of thrombin in promoting fibroblast proliferation in the lungs in this disorder.
      Bronchoalveolar lavage fluid (BALF) thrombin concentrations were higher in ten
      patients with systemic sclerosis than in 12 healthy controls (14.6 vs 3.6 nmol/L,
      p < 0.02), but values in patients with cryptogenic fibrosing alveolitis (n = 10)
      or sarcoidosis (n = 10) were not increased. BALF from all patients induced
      fibroblast proliferation. This proliferation was attenuated by thrombin
      inhibitors for BALF from systemic sclerosis patients only. We suggest thrombin
      contributes to lung fibroblast proliferation in this disorder.

PMID- 7564790
TI  - Endogenous synthesis of galactose in normal men and patients with hereditary
      galactosaemia.
AB  - Despite restricted ingestion of lactose, patients with galactose-1-phosphate
      uridyltransferase deficiency have raised concentrations of galactose metabolites
      in blood and urine. Endogenous production of galactose may underlie this
      phenomenon. Using isotopically labelled galactose in a continuous intravenous
      infusion, we employed the steady-state flux method to calculate endogenous
      galactose production rate in three normal men and three patients with classic
      galactosaemia. We found that galactosaemic patients and normal subjects
      synthesise gram quantities of galactose per day. The rate of synthesis ranged
      from 0.53-1.05 mg/kg per h. Endogenous production of galactose may be an
      important factor in the pathogenesis of the complications of the brain and ovary,
      and could explain the persistent elevation of galactose metabolites in patients
      despite dietary restriction of galactose.

PMID- 7564791
TI  - Introduction to neural networks.

PMID- 7564792
TI  - Prevention of diabetic renal disease with special reference to microalbuminuria.

PMID- 7564793
TI  - Comparing methods of measurement: why plotting difference against standard method
      is misleading.
AB  - When comparing a new method of measurement with a standard method, one of the
      things we want to know is whether the difference between the measurements by the
      two methods is related to the magnitude of the measurement. A plot of the
      difference against the standard measurement is sometimes suggested, but this will
      always appear to show a relation between difference and magnitude when there is
      none. A plot of the difference against the average of the standard and new
      measurements is unlikely to mislead in this way. We show this theoretically and
      by a practical example.

PMID- 7564794
TI  - Republicans' swift health-legislation moves.

PMID- 7564795
TI  - Way paved for HIV settlement talks in Japan.

PMID- 7564796
TI  - GMC revises guidelines.

PMID- 7564797
TI  - Sex chromosome abnormalities after intracytoplasmic sperm injection.

PMID- 7564798
TI  - Sex chromosome abnormalities after intracytoplasmic sperm injection.

PMID- 7564799
TI  - Sex chromosome abnormalities after intracytoplasmic sperm injection.

PMID- 7564800
TI  - Sex chromosome abnormalities after intracytoplasmic sperm injection.

PMID- 7564802
TI  - Bacteroides fragilis infection of a knee prosthesis after haemorrhoidectomy.

PMID- 7564801
TI  - Sex chromosome abnormalities after intracytoplasmic sperm injection.

PMID- 7564803
TI  - Tear injuries and upper endoscopy.

PMID- 7564804
TI  - Changing epidemiology of dengue in Singapore.

PMID- 7564806
TI  - Treatment of tuberculosis in developing countries.

PMID- 7564805
TI  - Treatment of tuberculosis in developing countries.

PMID- 7564807
TI  - Treatment of tuberculosis in developing countries.

PMID- 7564809
TI  - Contents of "ecstasy".

PMID- 7564808
TI  - Hazard to pathologists and anatomists from vena-caval (Greenfield) filters.

PMID- 7564810
TI  - Salbutamol in the treatment of asthma.

PMID- 7564811
TI  - Bayer promotional publications misleading about effect of ciprofloxacin on
      hospital admissions.

PMID- 7564812
TI  - Secondary transmission of HIV by aware seropositives.

PMID- 7564813
TI  - Clinical staging system for AIDS patients.

PMID- 7564814
TI  - Prediction by Humble of correction of thalassaemia and haemoglobin-E disease.

PMID- 7564815
TI  - Hyperammonaemia in cirrhosis and Helicobacter pylori infection.

PMID- 7564816
TI  - Treatment of warfarin-induced hair loss with ubidecarenone.

PMID- 7564818
TI  - NSAIDs, Cox-2 inhibitors, and the gut.

PMID- 7564817
TI  - NSAIDs, Cox-2 inhibitors, and the gut.

PMID- 7564819
TI  - Fibrosing colonopathy in a child on low-dose pancreatin.

PMID- 7564820
TI  - Epidemiology of rugby football injuries.

PMID- 7564821
TI  - Genetic variation of 5-HT2A receptor and response to clozapine.

PMID- 7564822
TI  - Simple measure of insulin resistance.

PMID- 7564823
TI  - Transluminal vascular stents for ostial atherosclerotic renal artery stenosis.

PMID- 7564824
TI  - Transluminal vascular stents for ostial atherosclerotic renal artery stenosis.

PMID- 7564825
TI  - Paromomycin for nitroimidazole-resistant trichomonosis.

PMID- 7564826
TI  - Tonsillectomy.

PMID- 7564827
TI  - Balancing community and academic health center needs while preserving educational
      quality.

PMID- 7564828
TI  - Surgical treatment of cervicofacial nontuberculous mycobacterial adenitis in
      children.
AB  - Fifteen children with nontuberculous mycobacterial adenitis of the head and neck
      underwent surgical treatment between July 1991 and July 1994. Fine-needle
      aspiration for biopsy and culture allowed early diagnosis in nine children.
      Positive cultures grew Mycobacterium avium-intracellulare complex in 12 children
      and M. chelonei in one child. Total excision was performed in 10 cases with
      combinations of lymphadenectomy and salivary gland excision. Curettage was used
      to successfully treat five children. One patient required local flap coverage for
      primary wound repair. Two patients required more than one surgical procedure. Our
      approach to early diagnosis and surgical treatment of cervicofacial
      nontuberculous mycobacterial adenitis is presented.

PMID- 7564829
TI  - Complications of endoscopic sinus surgery in a residency training program.
AB  - Endoscopic sinus surgery (ESS) is now taught in most otolaryngology residency
      programs in the United States. However, this is technically challenging surgery
      and concerns exist regarding patient safety early in the surgeon's learning
      curve. The authors reviewed 193 cases of ESS performed by residents, under
      faculty supervision at our program, between 1987 and 1992. Sixty-seven percent of
      patients underwent bilateral anterior ethmoidectomy, 40% had bilateral total
      ethmoidectomy, and 44% had bilateral middle turbinate reduction. The overall
      complication rate was 22% and included one major complication. Synechiae
      accounted for 50% of minor complications. There was no correlation between middle
      or inferior turbinate reduction and the formation of synechiae. Posterior
      ethmoidectomy was not associated with a significant increase in complications. We
      conclude that ESS can be safely performed by otolaryngology residents in
      carefully structured and supervised training programs.

PMID- 7564830
TI  - Snare uvulopalatoplasty.
AB  - Single-stage outpatient treatment of snoring with snare dissection
      uvulopalatoplasty (UPP) has been developed and found to be safe and effective.
      Single-stage snare dissection UPP (SUPP) was performed on 25 habitual loud
      snorers with readily available instrumentation in an ambulatory setting. Fourteen
      had associated septoplasty. When only SUPP was performed, local and topical
      anesthesia and minimal oral premedication were used in most cases. No significant
      immediate or delayed bleeding occurred. Postoperative discomfort persisted for 3
      to 12 days and required only oral analgesics. No postoperative complications
      occurred. Ninety-one percent of patients reported satisfactory reduction or
      elimination of snoring after surgery. Preoperative and postoperative acoustic
      analysis of sleeping respiration (SNAP testing) was used to document the effects
      of SUPP in eight patients. SUPP is a safe, cost-effective method of treating
      patients with habitual snoring.

PMID- 7564832
TI  - Vascularized auricular perichondrium in airway reconstruction: the effects of
      stenting with and without a mucosal graft.
AB  - This study quantitatively examines the effects of laryngotracheal stenting with
      and without mucosal grafting on chondrogenesis in a rabbit model. Vascularized
      auricular perichondrium was transferred to a cricothyroid membrane (CTM) defect
      in three groups of New Zealand white rabbits: group A, CTM defect alone; group B,
      CTM defect with endotracheal tube stent; and group C, CTM defect with a buccal
      mucosa graft (BMG) interposed between the stent and perichondrium. The rabbits
      were sacrificed at 7 weeks for histologic examination and determination of
      cartilage thickness by digitometry. Chondrogenesis was not significantly affected
      by stenting (n = 11; 0.719 mm +/- 0.203 mm) or by BMG (n = 12; 0.775 mm +/- 0.203
      mm) as compared with controls (n = 14; 0.695 mm +/- 0.216 mm) (P value = not
      significant). Laryngotracheal stenting and BMG do not adversely influence
      chondrogenesis in airway reconstruction with vascularized perichondrium in the
      rabbit model. The application of these principles in human airway reconstruction
      is discussed.

PMID- 7564831
TI  - Advanced techniques in magnetic resonance imaging in the evaluation of the large
      endolymphatic duct and sac syndrome.
AB  - The purpose of this report is to compare temporal bone computed tomography (CT)
      to high-resolution magnetic resonance (MR) imaging using a novel thin-section
      fast spin echo (FSE) pulse sequence in identifying and characterizing patients
      with large vestibular aqueduct syndrome. Sixteen patients with sensorineural
      hearing loss and a CT diagnosis of large vestibular aqueduct(s) underwent high
      resolution fast spin echo magnetic resonance imaging with dual, 3-in phased array
      receiver coils centered over the external auditory canals. Magnetic resonance
      imaging parameters included axial and oblique sagittal fast spin echo with an
      effective slice thickness of 1 mm contiguous. Thirty-eight patients with 76
      normal inner ears who underwent MR imaging using this technique had their
      endolymphatic duct measured. MR alone identified the enlarged endolymphatic sac
      seen along with the large endolymphatic duct in all cases. Three cases (five
      inner ears) with enlarged bony vestibular aqueducts on CT showed no evidence of
      endolymphatic duct or sac enlargement on MR. MR alone identified a single case of
      mild cochlear anomaly in conjunction with an enlarged endolymphatic duct and sac.
      In the normal population the size of the normal endolymphatic duct at its
      midpoint measured from 0.1 to 1.4 mm. Thin-section, high-resolution fast spin
      echo MR imaging of the inner ear may be superior to CT in the evaluation of
      patients with the large vestibular aqueduct syndrome.

PMID- 7564834
TI  - Gunshot injuries of the temporal bone.
AB  - Despite an increasing incidence of gunshot wounds to the temporal bone, there is
      little in the literature regarding management of survivors of these serious
      injuries. Twelve patients were treated for such wounds between 1986 and 1994. The
      most frequent presentations were cranial nerve injury, especially facial
      paralysis (9 patients), hearing loss (7), vascular injury (4), and vestibular
      dysfunction (3). Persistent cerebrospinal fluid otorrhea was uncommon (1 patient)
      in this series. Computed tomography and audiovestibular testing were helpful in
      evaluating the severity of injury and guiding the surgical approach when
      necessary. Electroneurography was helpful in evaluating facial nerve function;
      however, documented disruption of the facial nerve canal in itself was considered
      an indication for surgical exploration. Other indications for surgical
      intervention included evidence of dural tear, vascular injury, and severe
      disruption of the external auditory canal.

PMID- 7564833
TI  - Vocal fold medialization using autologous cartilage in a canine model: a
      preliminary study.
AB  - Unilateral vocal fold paralysis can alter phonation. Medialization of the vocal
      fold using cartilage augmentation dates to the early 1950s. Improved phonation
      after cartilage chordal augmentation has been reported, but no study has as yet
      documented cartilage viability or size in this setting over time. The authors of
      this study evaluated thyroid alar cartilage as a medializing material in three
      mongrel dogs. Grafts were inserted lateral to the inner thyroid perichondrium at
      the vocal fold level via a window in the thyroid cartilage. Changes in weight,
      size, and volume were assessed 6 months after implantation. The average graft
      weight declined by 15%, and the average square area declined by 3%. Importantly,
      the average volume maintained was 87%. The grafts remained rigidly fixed to the
      thyroid cartilage in their placement positions. Histologic examination documented
      minimal resorption. The data suggest that thyroid alar cartilage is a viable
      filler in type I thyroplasty procedures.

PMID- 7564835
TI  - Bacteriology of sinusitis in human immunodeficiency virus-positive patients:
      implications for management.
AB  - The bacteriology of sinusitis in human immunodeficiency virus (HIV)-infected
      patients has been only sporadically reported. In this study, we report the
      results of cultures taken from 12 HIV patients with refractory chronic sinusitis
      who underwent surgery. Nine of the 12 patients had positive cultures with 16
      isolates and 5 patients having multiple isolates. Five of the 12 patients grew
      out atypical or opportunistic infections not responsive to standard medical
      therapy, including 3 patients with cytomegalovirus, 1 with Aspergillus fumigatus,
      and 1 with Mycobacterium kansasii. These results suggest the need for aggressive
      medical care for HIV-infected patients with sinusitis and early intervention for
      tissue cultures in patients who do not respond to standard antibiotic regimens.

PMID- 7564836
TI  - Peroneal motor nerve crush injury and hyperbaric oxygen effect.
AB  - The potential therapeutic effect of hyperbaric oxygen (HBO) after rat peroneal
      nerve crush was evaluated. Animals were given 100% oxygen at 2.5 atmosphere
      absolute for 90 minutes twice daily for 1 week and then once daily for 1 week.
      Edema increased in crushed nerves compared with control nerves, but no effect was
      associated with the administration of HBO. Gait analysis demonstrated injury at
      1, 7, and 14 days after nerve crush, but no difference was found at 22 and 28
      days after injury (analysis of variance: P < .001, 10 animals per group). Eight
      weeks after injury, nerve stimulation and muscle force measurements were 114 g
      for the injured group and 146 g for the control group (P < .001). There were no
      HBO-associated changes in gait parameter or nerve/muscle force measurements. This
      study demonstrated that rat peroneal nerve crush injury causes acute intraneural
      edema and temporary decrement of gait parameters. Elicited nerve stimulation
      demonstrated persistent loss of force 4 weeks after normalization of gait, but no
      HBO effect.

PMID- 7564837
TI  - Preoperative identification of patients at risk for delirium after major head and
      neck cancer surgery.
AB  - This study was performed to determine preoperative criteria for identifying
      patients at risk for delirium after major head and neck cancer surgery. The
      authors prospectively evaluated 138 consecutive patients undergoing head and neck
      cancer surgery lasting more than 2 hours at the Arthur G. James Cancer Hospital
      and Research Institute, Ohio State University, Columbus, from July 1993 through
      May 1994. Postoperative delirium developed in 24 of 138 patients (17%; 95%
      confidence interval 11% to 24%). The strongest univariate predictors of delirium
      were living alone (P = .005), the American Society of Anesthesiologists class (P
      = .003), and the preoperative white blood cell count (P < .0001). A predictive
      model for delirium using five criteria--age of 70 or more years, alcohol abuse,
      poor cognitive status, poor functional status, and markedly abnormal serum
      sodium, potassium, or glucose level--stratified the patients into three cohorts
      with an increasing risk of postoperative delirium (i.e., 9%, 19%, and 25%).

PMID- 7564838
TI  - The role of magnetic resonance angiography in head and neck surgery.
AB  - Magnetic resonance angiography (MRA) is a recently developed, noninvasive
      vascular imaging technique. The authors of this investigation assessed the
      diagnostic value of MRA, along with its influence on therapeutic decisions, in 11
      patients with a variety of head and neck disorders. In 5 patients, MRA diagnosed
      or ruled out an intrinsic vascular lesion. MRA was used to evaluate 5 of 8
      patients with cancer for evidence of direct tumor involvement of vascular
      structures. Other uses of MRA included preoperative determination of tumor
      vascularity and delineation of anatomic relationships between normal vessels and
      head and neck pathology. Overall, MRA results guided management in 10 patients,
      and in some cases it determined the extent of surgical intervention. Because MRA
      is safer and more practical than traditional angiography, the authors recommend
      more frequent use of this imaging technique in the practice of head and neck
      surgery.

PMID- 7564839
TI  - A murine model for the immunotherapy of head and neck squamous cell carcinoma.
AB  - A murine model for the immunotherapy of head and neck cancer was established. The
      AT-84 tumor, a spontaneously arising oral squamous cell tumor of C3H mice, was
      evaluated for susceptibility to lymphokine-activated killer (LAK) cells. In vitro
      chromium-release assays demonstrated that AT-84 is sensitive to LAK-cell-mediated
      killing. Furthermore, in vivo experiments employing a lung metastasis model
      demonstrated a 50% reduction in the number of metastases in LAK-cell-treated mice
      as compared with untreated controls (P2 = .001). These experiments showed that AT
      84 is an appropriate model for the immunotherapy of head and neck cancer. This
      model should be invaluable for further study of the mechanisms involved in immune
      mediated therapy of head and neck cancer.

PMID- 7564840
TI  - Head and neck surgery workforce in the year 2014.
AB  - The head and neck surgery workforce in the United States over the next 20 years
      is of significant interest to physicians, patients, and others. Using election to
      fellowship in the American Society for Head and Neck Surgery or the Society of
      Head and Neck Surgeons, or both, as the criteria for designation as a head and
      neck surgeon, a mathematical model was designed to project the growth of the head
      and neck surgery workforce through the year 2014. The current combined active
      membership of the two societies was analyzed to determine the impact of age
      distribution on this model. The paradigm assumes 30 new head and neck surgeons
      each year and includes the appropriate mortality rate for each cohort. Based on
      this model, the total number of head and neck surgeons should decrease slightly
      from 1109 in the year 1994 to 1028 in the year 2014. A steady-state supply of
      head and neck surgeons is therefore predicted.

PMID- 7564842
TI  - Functional outcome after surgery for prevention of pharyngospasms in
      tracheoesophageal speakers. Part I: Speech characteristics.
AB  - The speech characteristics of 29 patients with primary tracheoesophageal puncture
      who received either a pharyngeal constrictor myotomy, a unilateral pharyngeal
      plexus neurectomy, or a unilateral pharyngeal plexus neurectomy with drainage
      myotomy limited to the cricopharyngeus were studied. All patients used a Blom
      Singer low-pressure voice prosthesis. Audio recordings of each patient speaking
      with both the Blom-Singer tracheostoma valve and manual occlusion of the
      tracheostoma were recorded at 3 weeks, 6 months, and 12 months after surgery. The
      three surgical variations were equally effective at preventing pharyngospasms;
      only 1 patient (10%) in each group had some loss of fluency during the 12-month
      study period. Neurectomized patients produced significantly higher fundamental
      frequencies during reading than did patients in the other groups. Residual
      resting tone in the neurectomized pharyngoesophageal segment may contribute to
      more favorable speaking frequencies in this group.

PMID- 7564841
TI  - Management of carotid artery rupture by monitored endovascular therapeutic
      occlusion (1988-1994).
AB  - The reported mortality (40%) and neurologic morbidity (25%) rates for carotid
      rupture remain unacceptably high. This study was conducted to assess the impact
      of endovascular detachable balloon occlusion and the changing characteristics of
      carotid rupture in head and neck surgery. Between January 1, 1988, and June 30,
      1994, 18 carotid ruptures were identified in 15 patients. Etiologic factors
      included radical surgery, radiation therapy, wound complications, and recurrent
      or persistent carcinoma. In 15 of 18 instances of carotid rupture, patients
      survived without major neurologic sequelae. After the introduction of
      endovascular techniques in 1991, the 12 patients whose hemorrhage was
      definitively managed through permanent balloon occlusion survived without
      significant neurologic sequelae. Endovascular occlusion techniques in the
      monitored patient may significantly improve the outcome after carotid rupture.

PMID- 7564843
TI  - Functional outcome after surgery for prevention of pharyngospasms in
      tracheoesophageal speakers. Part II: Swallow characteristics.
AB  - The swallowing function of 29 patients with primary tracheoesophageal puncture
      who received either a pharyngeal constrictor myotomy, a unilateral pharyngeal
      plexus neurectomy, or a unilateral pharyngeal plexus neurectomy with a small
      drainage myotomy limited to the cricopharyngeus was studied. Swallowing function
      data were collected on each patient at 3 weeks, 6 months, and 12 months after
      surgery using videofluoroscopy. Differences in swallowing function among the
      treatment groups were primarily the amounts and loci of oral and pharyngeal
      residues. The differing patterns of bolus residue may reflect the different
      mechanisms that were affected by the various procedures. Despite significant
      changes in some swallow measures, the patients did not complain of dysphagia.
      Oropharyngoesophageal swallow efficiency--a clinical measure that weighs the
      amount of bolus swallowed by total transit time--fell within normal limits for
      each patient group at each evaluation. This measure may be a better index of the
      patients' perceived normal swallow than the component variables of residue and
      transit times would suggest.

PMID- 7564844
TI  - Severe laryngomalacia: surgical indications and results in 115 patients.
AB  - Between 1987 and 1993, 115 children were operated on for severe forms of
      laryngomalacia in two pediatric ear, nose, and throat (ENT) departments. The
      criteria used to determine the severity of the illness were selected following
      short hospitalization periods during which the children received both pediatric
      and ENT checkups. Based on clinical manifestations and/or the results of pH
      monitoring gastroesophageal reflux was found to be present in 68% of the children
      in the study. Detailed analysis and endoscopy were used to differentiate the
      symptoms that were related to laryngomalacia from those that were caused by other
      conditions, including mixed-breathing, swallowing, and sucking difficulties.
      Endoscopic resection of the aryepiglottic folds, with or without the use of a
      carbon dioxide laser, resulted in rapid improvement of both ventilation and
      swallowing. The success rate of this simple and effective procedure, which has no
      inherent morbidity, was 98% in an average follow-up period of 30 months. Only
      seven children required an additional similar procedure. The procedure failed in
      only two children, who needed to be tracheotomized. Given these excellent
      results, endoscopic resection can be considered an effective technique for the
      management of severe laryngomalacia.

PMID- 7564845
TI  - The natural history of globus pharyngeus.
AB  - While globus pharyngeus is a common disorder, accounting for 3% to 4% of new
      otolaryngology outpatient referrals, few long-term follow-up studies have been
      conducted on patients with this condition. The authors of this study followed 74
      patients with a diagnosis of globus pharyngeus for an average of 7 years, 7
      months (range: 7 years to 8 years, 10 months). During the follow-up period, 55%
      of patients were asymptomatic and 45% of patients had persistent symptoms. An in
      depth analysis of features at clinical presentation failed to reveal any reliable
      prognostic indicators. A number of patients developed other conditions during the
      follow-up period, but no patient developed upper aerodigestive tract malignancy.
      This study represents the longest follow-up of globus patients to date and, to
      the authors' knowledge, is the first to address the issue of malignancy in
      globus.

PMID- 7564846
TI  - Nodal inclusion cysts of the parotid gland and parapharyngeal space: a discussion
      of lymphoepithelial, AIDS-related parotid, and branchial cysts, cystic Warthin's
      tumors, and cysts in Sjogren's syndrome.
AB  - The purpose of this report is to examine the computed tomography scans, magnetic
      resonance images, and pathologic findings in 44 patients, 42 of whom had
      inclusion-type cysts of the parotid and parapharyngeal space of varying
      etiologies. Two additional cases of cystic changes in the benign lymphoepithelial
      lesion (BLEL) of Sjogren's syndrome are highlighted here, since they had
      unusually large cystic components mimicking acquired immunodeficiency syndrome
      related parotid cysts (ARPCs). A retrospective examination identified 18 ARPCs, 3
      lymphoepithelial cysts (LECs), 13 cystic Warthin's tumors, 8 branchial cysts, and
      2 cases of cysts in patients with Sjogren's syndrome (BLEL), all of whom had
      imaging studies and pathologic confirmation. There were 30 men and 14 women with
      an age range of 25 to 72 years (median, 46.82 years). Any similarities in the
      imaging appearances were noted, as were any differences in pathologic detail. On
      imaging, only the cystic Warthin's tumors had any focal wall nodularity; the
      other cysts had smooth walls. When multiple parotid cysts were present, the
      distinguishing feature between ARPCs and cysts in BLEL (and some cystic Warthin's
      tumors) was the presence of diffuse cervical adenopathy in patients with ARPCs.
      Imaging usually could not differentiate between a solitary parotid LEC, a
      branchial cyst, and some cystic Warthin's tumors. Extraparotid lesions were
      either branchial cysts or cystic Warthin's tumors. Physicians should be aware of
      the variety of different inclusion-type cysts that may occur in the parotid gland
      and parapharyngeal space, all of which may have similar imaging appearances.
      Although imaging clearly identifies these cysts and may suggest a specific
      diagnosis, it must always be remembered that the precise diagnosis remains in the
      province of the pathologist.

PMID- 7564847
TI  - Reconsidering a paradigm: the spread of supraglottic carcinoma to the glottis.
AB  - This study was performed to evaluate the spread of supraglottic carcinoma to the
      glottic level. Whole organ sections of total laryngectomy specimens from 37
      patients with previously untreated supraglottic carcinomas were reviewed
      retrospectively. Of the 37 specimens, 20 (54%) were noted to have extension of
      cancer to the glottic level. A significant relationship was noted between glottic
      extension and abnormal cord motion (P = .0002). A statistically significant trend
      was noted for the relationship between inferior extension along the supraglottic
      mucosa and glottic level extension (P < .0001). Contrary to the prevailing model
      of the spread of supraglottic carcinoma, in which there is a distinct barrier to
      spread at the ventricle, this analysis of selected supraglottic carcinomas
      revealed a continuum of spread from the supraglottic to the glottis.

PMID- 7564848
TI  - Botulinum toxin type A injection for hyperfunctional facial lines.

PMID- 7564849
TI  - The free bone flap approach to the frontal sinus in the high-risk orbital
      patient.

PMID- 7564851
TI  - Directory of otolaryngological societies.

PMID- 7564850
TI  - Reconstruction of the total columellar defect.

PMID- 7564852
TI  - Reduction rhinoplasty.

PMID- 7564854
TI  - Role of the Alexandrite laser for removal of tattoos.
AB  - BACKGROUND AND OBJECTIVE: The development of the Alexandrite laser for the
      removal of blue-black tattoos is described. STUDY DESIGN/MATERIALS AND METHODS:
      The responses of an animal study, using professionally tattooed skin and a human
      study involving 22 (professional and nonprofessional) blue-black tattoos, to the
      Alexandrite laser are reported. RESULTS: Histopathologic evaluation of tattooed
      pig skin biopsies demonstrated the method of removal of dermal tattoo pigment. An
      average 11.6 treatments were required to remove completely the ten human blue
      black professional tattoos compared to an average of 10.3 treatments to reach the
      same endpoint in six subjects with nonprofessional tattoos. CONCLUSION: Of
      significance was the fact that unlike the Q-switched Ruby and Nd:YAG lasers where
      punctate bleeding and tissue splattering have been reported to occur during laser
      tattoo removal, epidermal integrity was maintained during exposure of tattooed
      skin to the Q-switched Alexandrite laser at therapeutic fluences used.

PMID- 7564853
TI  - Clinical and preclinical photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a treatment modality that utilizes a
      photosensitizing drug activated by laser generated light, and is proving
      effective for oncologic and nononcologic applications. This report provides an
      overview of photosensitizers, photochemistry, photobiology, and the lasers
      involved in photodynamic therapy. Clinical and preclinical PDT studies involving
      Photofrin and various second generation photosensitizers are reviewed.

PMID- 7564855
TI  - Ultrastructural alterations in heated canine myocardium.
AB  - BACKGROUND AND OBJECTIVE: The anisotropy factor of light scattering (g)
      (wavelength 632.8 nm) in heated myocardium decreases as a function of
      temperature, suggesting, on the basis of Mie theory of light scattering,
      formation of an increasing number of particles with diameters smaller than the
      incident wavelength. STUDY DESIGN/MATERIALS AND METHODS: To test this hypothesis,
      fresh myocardium was heated at constant temperatures between 37 degrees C and 75
      degrees C for 1,000 s. Changes in size and number of granules generated by
      disintegrating organelles and sarcomeres were studied as a function of
      temperature by transmission electron microscopy, planimetry and particle
      counting. RESULTS: The mitochondria started to disintegrate at 45 degrees C and
      myofibrils between 45 degrees C and 50 degrees C into increasing numbers of small
      electron dense granules (diameter 50-200 nm), which correlated with the observed
      decrease of g from 0.93 +/- 0.02 (at room temperature to 45 degrees C) to 0.77 +/
      0.05 at 75 degrees C. CONCLUSION: The scattering coefficient microseconds of 161
      +/- 33 cm-1 did not change significantly.

PMID- 7564856
TI  - Laser photocoagulation of prostate: influence of dosimetry.
AB  - BACKGROUND AND OBJECTIVE: Recently, increasing enthusiasm has been shown for
      application of lasers for the treatment of benign prostate hyperplasia (BPH).
      However, little is known about the thermodynamics of prostatic tissue response
      during laser irradiation and how the treatment outcome can be optimized. Our
      objective was to conduct a systematic study of the influence of exposure
      parameters on the extent of tissue coagulation and to determine the effects of
      rate of tissue heating on lesion size by comparing the tissue response to high
      laser power rapid heating vs. low laser power slow heating. STUDY
      DESIGN/MATERIALS AND METHODS: Nd:YAG laser irradiation of prostate was performed
      in 15 mongrel canines, using an incident power of 15, 30, or 50 Watts (at the
      fiber tip) and an exposure time varying from 30 to 300 seconds. The laser beam
      was delivered via a Urolase side-emitting catheter. The tissue response was
      compared based on gross as well as histological evaluations of thermal lesions.
      RESULTS: The depth of coagulation necrosis increased as the laser power was
      reduced from 50 W to 30 W and further to 15 W while the total delivered energy
      was kept constant at 2,700 J by adjusting the exposure time. The difference
      between the three heating rates was more dramatic when the estimated volume of
      coagulated tissue was considered. Increasing the irradiation time for the low
      power (15 W) from 180 to 300 seconds resulted in enlarging the coagulated volume
      by a factor of 1.6. However, for high power (50 W), increasing the exposure time
      from 54 to 90 seconds resulted in increasing the coagulated volume by a factor of
      1.2. CONCLUSION: This study suggests that a slow heating regimen yields larger
      volumes of coagulation necrosis than the currently used rapid heating approach.

PMID- 7564857
TI  - Creation of a volume lesion in the dog prostate using neodymium:YAG laser
      coagulation: concepts for clinical treatment.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to determine the
      geometrical development of a coagulated zone in the canine prostate during free
      beam side fire Nd:YAG laser coagulation. STUDY DESIGN/MATERIALS AND METHODS: A
      series of 10 male dogs underwent endoscopic prostatic Nd:YAG fixed position laser
      coagulation through a suprapubic cystotomy using a right-angle deflecting
      delivery catheter (Microvasive, Boston, MA) at times varying from 10 to 120
      seconds at 30 watts. In addition, two dogs underwent lasing by pulling the
      catheter at 1 mm/s in four quadrants. Acute gross and microscopic pathology
      specimens were prepared and the lesion shape and volume determined. RESULTS:
      Analysis of the coagulated volume showed that during the initial 15 seconds of
      lasing, the zone of coagulation approximates a sphere centered on the urothelium
      opposite the laser fiber. However, as lasing progressed, the lesion changed from
      a sphere to an expanding ellipse. This changing geometry can be explained by the
      absorption and scatter characteristics of the laser and the temperature
      equilibrium that is established within the prostate. CONCLUSION: An understanding
      of this time-dependent geometrical shift from a sphere to an ellipse allows the
      surgeon to supplement the fixed protocols for lasing at certain positions for
      given amounts of time. Specific plans can then be established for tissue at the
      bladder neck, apex, anterior stroma, floor, and irregular prostatic regrowth.

PMID- 7564858
TI  - Superior nerve anastomosis using a low-output CO2 laser on fibrin membrane.
AB  - BACKGROUND AND OBJECTIVE: To date, no procedure of laser-aided nerve anastomosis
      has yet proved to be consistently superior to suture nerve repair. This study
      examines a new method for nerve repair using a low output CO2 laser and fibrin
      membrane to ascertain the efficacy of this method for nerve regeneration in
      comparison with the suture method. STUDY DESIGN/MATERIALS AND METHODS: Both
      sciatic nerves of 42 Wister rats were used. The left sciatic nerves were cut and
      reconnected using 70 mW of irradiation on fibrin membrane bridging the nerve
      stumps, whereas the right sciatic nerves were repaired with two stitches of
      epineuro-fascicular sutures. RESULTS: No deleterious effect of the irradiation on
      nerve regeneration was demonstrated at any time after surgery. The number of
      myelinated axons larger than 5 microns in diameter and the mean diameter of
      mylinated axons 8 weeks after surgery were significantly larger in the laser
      group than those in the suture group (P < 0.05). CONCLUSION: The results suggest
      this new method may be useful and effective for clinical nerve repair.

PMID- 7564859
TI  - Double-blind, placebo-controlled investigation of the effect of combined
      phototherapy/low intensity laser therapy upon experimental ischaemic pain in
      humans.
AB  - BACKGROUND AND OBJECTIVE: This study assessed the putative analgesic effect of
      combined monochromatic light/laser irradiation at low intensity (660-950 nm; 31.9
      J/cm2; pulsed at 16 or 73 Hz). STUDY DESIGN/MATERIALS AND METHODS: The
      investigation was completed under double-blind conditions using a standardised
      form of the submaximal effort tourniquet technique. Healthy male volunteers naive
      to the experimental conditions (n = 45) attended on two occasions for the
      purposes of pain induction, the first during which baseline data were obtained
      and on a second occasion during which they were randomly allocated to one of two
      treatments or a placebo condition. For the treatment conditions, irradiation was
      applied to the ipsilateral Erb's point at the parameters stated; for the placebo
      condition, sham "irradiation" was delivered using a dummy unit. Pain was measured
      using computerised visual analogue scales and McGill Pain Questionnaires (MPQ) to
      assess "current pain intensity" and "worst pain experienced," respectively.
      RESULTS: Analysis of variance and appropriate post hoc tests demonstrated only a
      weak (but significant) hypoalgesic effect compared to placebo (P < 0.05) in the
      treatment group irradiated at 16Hz for the sensory component of the MPQ; other
      comparisons were found to be nonsignificant. CONCLUSIONS: These results do not
      provide convincing evidence for the hypoalgesic potential of combined
      monochromatic light/laser irradiation, at least at the parameters used here, and
      thus indicate the necessity of additional work to investigate this modality
      further in order to assess the potential benefit, if any, of such treatment in
      the clinical setting.

PMID- 7564860
TI  - Spot size reduction in coupling of laser to micromanipulator in laser
      microsurgery by fiberoptic link.
AB  - BACKGROUND AND OBJECTIVE: In coupling laser with micromanipulator through
      fiberoptics, the resulting diameter of the spot is limited by the laws of
      geometrical optics, because of the high numerical aperture (N.A.) of fiberoptic
      radiation. A new method for the reduction of spot size diameter is suggested.
      STUDY DESIGN/MATERIALS AND METHODS: The output of a 2 mW He-Ne laser was couped
      via fiberoptic link, the fiberoptic output light collected by a single lens
      collimator and directed to the input of the micromanipulator. RESULTS: The spot
      size can be considerably reduced by the introduction of an aperture which reduces
      the numerical aperture (N.A.) of the fiberoptic. The resulting reduction in total
      power has little effect on the power density. CONCLUSION: This approach to the
      collimator design permits reduction in spot size without any significant changes
      in power density, thus avoiding damage to the tissue and obtaining optimum
      performance from the micromanipulator.

PMID- 7564861
TI  - [Once again: "A sick federal health office watches over health!"].

PMID- 7564863
TI  - [Who is affected by blindness?].

PMID- 7564862
TI  - [Federal health office commentaries: false, misleading citations].

PMID- 7564864
TI  - [What is the effect of omeprazole in acute peptic ulcer hemorrhage?].

PMID- 7564865
TI  - [Long-term therapy with omeprazole: when will it finally be approved?].

PMID- 7564866
TI  - [Treatment error, negligent physical injury and negligent homicide].

PMID- 7564868
TI  - [What can be learned from this case?].

PMID- 7564867
TI  - [We hope that the responsible persons learn from the experience!].

PMID- 7564869
TI  - [Gastroesophageal reflux: current status of therapy].
AB  - The aim in treatment of reflux oesophagitis is to relieve symptoms as well as to
      prevent complications and recurrence of the disease. The obvious preventive
      measures as abstinence from alcohol and nicotine and to sleep in a raised bed are
      useful for the health of the patient in general, but application on a whole is
      not possible and their efficiency in therapy of reflux oesophagitis is
      questionable. As to pharmaceutical treatment, proton pump inhibitors are the
      first line therapy. Such treatment enables the raising of pH levels over 4 to
      enable efficient acid blocking. It works directly on the key enzyme without being
      influenced by other environmental factors. Proton pump inhibitors have few side
      effects and they are suitable for long term treatment. In comparison to other
      medications proton pump inhibitors have proved to be significantly better in
      reducing symptoms of reflux oesophagitis in a shorter time. They also reduce
      healing time of peptic lesions and have proved to be efficient in higher stages
      of reflux oesophagitis and even in cases resistant to H2-inhibitors. H2
      inhibitors have lost their place in the treatment of reflux oesophagitis with the
      arrival of proton pump inhibitors, because they are less effective, have a
      comparable number of side effects and are not prophylactic against relapse. Only
      patients complaining of reflux symptoms without provable morphological changes in
      the oesophago-gastral region are suitable for treatment with antacida or H2
      inhibitors. There is a strict indication for long term treatment in stages with
      severe morphological changes (stage III or IV according to Savary and Miller) and
      in prevention of symptomatical relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564871
TI  - [Complications of endoscopic sclerotherapy of esophageal varices].
AB  - Within the framework of a retrospective study complications of endoscopic
      variceal sclerotherapy were analyzed. From April, 1, 1988 till August, 31, 1994
      267 consecutive patients (158 male, 109 female, mean age 43 [27-78] years) with
      esophageal variceal hemorrhage due to liver cirrhosis and portal hypertension
      underwent endoscopic variceal injection treatment. Sclerotherapy was performed
      with 24.5 ml (12-34 ml) 1% of polydocanole on average per treatment. Each patient
      had 4.5 (2-7) therapy sessions on average. Local complications were: Transient
      dysphagia (73%), chest pain (65%), esophageal ulcerations (63%), ulerogenic
      bleeding (14%), posttherapeutic hemorrhage (13%), esophageal strictures (10%),
      pleural effusions (9%), subfebrile temperatures (6.4%), pericarditis (0.4%) and
      esophageal perforation (0.4%). No patient died from sclerotherapy-induced side
      effects. In conclusion, endoscopic injection therapy is an efficient treatment of
      acute variceal hemorrhage. Not severe local complications often occur, severe
      side effects are extremely rare, however.

PMID- 7564870
TI  - [Treatment of acute peptic gastroduodenal ulcer: omeprazole is superior to
      ranitidine especially in the early phase of ulcer healing. A prospective
      controlled randomized serial endoscopy study].
AB  - Omeprazole (OM) has been shown to be superior to H2-Blockers in terms of complete
      healing rates of gastric (GU) and duodenal ulcers (DU). We investigated in more
      detail the kinetics of ulcer healing under OM (20 mg mane) compared with
      ranitidine (RAN 300 mg nocte) in GU (n = 28) and DU (n = 27) by multiple series
      endoscopy. After endoscopic diagnosis (day 0) patients were allocated to either
      OM or RAN in a random order. Endoscopic controls were undertaken at day (d) 3, 7,
      14, 21, 28, 42 up to complete ulcer healing. The seize of ulcer areas was
      assessed by independent endocopists estimating the longest and shortest diameter
      D acc. to the formula A = pi x D1 x D2:4. RESULTS: In GU and DU cumulating
      healing rates were sign, higher under OM. In GU and DU, the most striking
      differences in the absolute and percentual reduction of ulcer seize in favour of
      OM vs RAN were observed mainly during the first week. At d3 under OM the
      reduction in DU-area was 43% and at d7 75% compared to a distinctly lower rate
      under RAN with the corresponding figures of 9% and 61% resp. In GU the mean
      reduction in area was for IM at d3 41%, at d7 82% in contrast to RAN at d3 of 34%
      and d7 of 49%. The faster healing during the first week was accompanied by sign
      more rapid reduction in day-and-night-painscore during OM vs RAN.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7564874
TI  - [Development of malignancies and chronic inflammations of the gastrointestinal
      tract--new concepts].

PMID- 7564872
TI  - [Anastomotic recurrence with tumor stenosis after Billroth II gastrectomy for
      adenocarcinoma: implantation of 2 metal stents as palliative therapy].
AB  - We report on a 70 year old patient with a great relapse in the region of the
      anastomosis after a palliative, subtotal gastrectomy with Billroth-II
      gastrojejunostomie because of an adenocarcinoma one year before. He was unable to
      swallow fluids or solid food. The possibility of a sufficient
      gastroenteroanastomosis was certainly limited (great tumor-mass left during
      operation). So we implantated two metal stents in the afferent and the efferent
      limb, respectively. The patient's vomiting completely relieved and he was able to
      swallow fluid food again. After that treatment the patient's quality of live
      noticeably increased. Furthermore, by stenting the afferent limb a sufficient
      drainage out of the duodenum could be reached, thereby preventing an increasing
      cholestasis.

PMID- 7564873
TI  - [Pedicled polypoid carcinosarcoma: a very rare esophageal tumor].
AB  - Neoplasms of the esophagus normally appear either as a exophytic-polypoid form,
      or as an infiltrating carcinoma or as an ulcerating tumor. We report on a 86 year
      old man suffering from the rare case of a pedicle polypoid tumor of the esophagus
      histologically diagnosed as a carcinosarcoma. We discuss the histological
      problems and our diagnostic and therapeutic proceeding.

PMID- 7564875
TI  - Effect of halofantrine and its desbutyl metabolite on lymphocyte proliferation
      dynamics.
AB  - Halofantrine hydrochloride (HF), one of the latest antimalarial agents currently
      undergoing clinical trials, and its active metabolite, N-desbutylhalofantrine
      (DHF), were examined for their effects on human and rat lymphocytes. HF has a
      biphasic concentration-dependent effect on phytohemagglutinin stimulated
      proliferation of human lymphocytes. Concentrations lower than 2.25 microM
      enhance, while higher concentrations inhibit proliferation. The IC50 values were
      9.4 microM for HF, 4.5 microM for DHF and 14.7 microM for chloroquine. In human
      lymphocytes, enhanced proliferation was not detected for DHF unlike for HF.
      Combined achievable plasma concentrations of HF and DHF may sometimes be in the
      range where reduced lymphocyte proliferation occurs in vitro when based on simple
      additive dynamics. It remains to be confirmed if malarial treatment with HF leads
      to reduced T-cell responsiveness to antigenic challenges since HF and DHF persist
      for several days.

PMID- 7564876
TI  - Antinociceptive activity of filenadol on inflammatory pain.
AB  - The novel analgesic filenadol (d, 1-erythro-1-(3',4'-methylenedioxyphenyl)-1-
      morpholinopropan-2-ol) inhibited phenyl-p-benzoquinone-induced writhing in mice
      with ID50 values of 68.8 (p.o.), 1.67 (i.v.) and 0.48 (i.c.v.) mg/kg.
      Hyperalgesia induced by arachidonic acid, PGE2 or LTB4 in this test was also
      decreased by filenadol (ID50 = 24.4, 3.7 and 50.1 mg/kg p.o., respectively). This
      compound was effective on PGE2, LTB4, bradykinin, PAF or IL-1 beta-induced
      decrease in pain threshold in the rat paw pressure model and almost totally
      suppressed the writhing induced by zymosan in mice, while peritoneal production
      of 6-ketoPGF1 alpha was inhibited by 48.5-62% and only at 100 mg/kg significant
      inhibition of LTC4 was achieved. The late phase of formalin-induced pain response
      in mice was prevented by filenadol, without affecting the oedema. Filenadol is an
      antinociceptive agent that reduces the hyperalgesic effects of inflammatory
      mediators besides inhibiting partially the synthesis of eicosanoids.

PMID- 7564878
TI  - Anti-inflammatory activity of amylin and CGRP in different experimental models of
      inflammation.
AB  - The anti-inflammatory activity of amylin was studied in different models of
      inflammation, and compared to that of CGRP. Both peptides were active against
      mouse ear oedema induced by croton oil and acetic acid-induced peritonitis in the
      rat. CGRP was more potent than amylin in both models. Pretreatment with CGRP 8-37
      fragment blocked the anti-inflammatory activity of both peptides in croton oil
      ear oedema. No anti-inflammatory activity was evidenced against serotonin-induced
      rat paw oedema and plasma protein extravasation induced by dextran in rat skin.
      Our results suggest that amylin exerts anti-inflammatory activity only in
      inflammatory models characterized by a vascular component. This effect appears to
      be mediated by the involvement of CGRP receptors.

PMID- 7564877
TI  - Comparison of two pet radioligands for imaging extrastriatal dopamine
      transporters in human brain.
AB  - We compared the sensitivity of two dopamine transporter (DAT) ligands ([C
      11]cocaine and [C-11]d-threo-methylphenidate) for measurement of extrastriatal
      DAT availability using positron emission tomography (PET) on separated groups of
      10 age matched male volunteers (age range, 21-49 years). DAT availability was
      obtained using the ratio of the distribution volume in the region of interest to
      that in the cerebellum (Bmax'/Kd'+ 1). DAT availability measured with [C-11]d
      threo-methylphenidate was highest in basal ganglia, followed by thalamus >
      temporal insula, cingulate > orbitofrontal, frontal and occipital cortices. A
      similar ranking order for DAT availability was obtained with [C-11]cocaine.
      Specific binding (Bmax'/Kd') of [C-11]cocaine in thalamus was 25-33% that of
      basal ganglia and [C-11]d-threo-methylphenidate in thalamus was 11-13% that of
      basal ganglia. The regional measures with [C-11]cocaine were significantly
      correlated with those of [C-11]d-threo-methylphenidate (p < or = 0.0001). These
      results document extrastriatal binding in human brain with two different DAT
      ligands.

PMID- 7564879
TI  - Measurement of nitric oxide synthase and its mRNA in genetically obese (ob/ob)
      mice.
AB  - Recent studies have suggested a role for nitric oxide (NO) in the regulation of
      food intake. The obese (ob/ob) mouse is a genetic model of obesity. Previously,
      it has been demonstrated that ob/ob mice show a marked weight reduction when
      treated with a nitric oxide synthase inhibitor. In the studies reported here, we
      demonstrate increased levels of nitric oxide synthase (NOS) and its mRNA in the
      hypothalamus of genetically obese (ob/ob) mice compared to their lean littermate
      controls (ob/c). NOS levels were 0.016 +/- 0.001 nmol/mg/min in ob/ob compared to
      0.009 +/- 0.001 in ob/c (p < 0.01) and NOS mRNA was 32.0 +/- 5.0 pg NOS mRNA/mg
      total RNA in ob/ob compared to 12.4 +/- 4.0 in ob/c (p < 0.05). These studies
      further support the possibility of a role for nitric oxide in the regulation of
      food intake.

PMID- 7564880
TI  - Spasmolytic and calmodulin inhibitory effect of non-steroidal anti-inflammatory
      drugs in vitro.
AB  - The effect of several anti-inflammatory drugs (NSAIDs), the calmodulin inhibitor
      W-7 and cortisol on vanadate-induced tonic contraction and on calmodulin
      dependent cAMP-phosphodiesterase activity have been assayed. Indomethacin,
      diclofenac, phenylbutazone, mefenamic acid, naproxen, tolmetin, piroxicam,
      aspirin and W-7, but not metimazol, produce dose-dependent relaxation of vanadate
      induced tonic contraction on isolated rat uterus. Cortisol relaxes the vanadate
      contraction up to 45%. None of the drugs assayed inhibit the basal activity of
      phosphodiesterase with concentrations lower than 1 mM. However, indomethacin,
      diclofenac, phenylbutazone, mefenamic acid, naproxen, piroxicam, aspirin and W-7
      inhibit, in a concentration-dependent way, the calmodulin-stimulated activity of
      phosphodiesterase. The maximum inhibition achieved with tolmetin (1 mM) and
      cortisol (1 mM) was 38% and 24%, respectively. Metamizol has no effect on basal
      or/and stimulated phosphodiesterase. This, as far as we know, is the first
      description of relationship between NSAIDs and calmodulin-dependent processes and
      our results suggest that the inhibition of calmodulin with NSAIDs may be directly
      related to their pKa and liposolubility.

PMID- 7564881
TI  - Involvement of polyamines in the contragestational effect of hyperthermia.
AB  - Although hyperthermia produces teratogenic effects in a great variety of animal
      species, the molecular mechanisms by which hyperthermia exerts its action remain
      unknown. We have studied the implications of polyamines in contragestational
      hyperthermia in rats. Our results show that the contragestational action of
      hyperthermia when applied in consecutive periods during days 8, 9 and 10 of rat
      pregnancy could be completely prevented by the previous administration of
      polyamines (putrescine and spermidine, 0.6 mmoles/kg and 0.03 mmoles/kg
      respectively) in combination with the diamine oxidase inhibitor aminoguanidine or
      by this inhibitor alone (0.12 mmoles/kg). The administration of polyamines alone
      partially prevented the fetotoxic effect of hyperthermia but produced a marked
      mortality (50%) in the pregnant rats. These findings support a major and complex
      role of polyamines in the mechanisms of hyperthermia-mediated teratogenesis, and
      suggest that the oxidative catabolism of polyamines could be in part responsible
      of the deleterious effect produced by hyperthermia in rat pregnancy.

PMID- 7564882
TI  - Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum
      melatonin. Role of duration and intensity of exposure.
AB  - The purpose of this study was to determine whether the exposure to a 50-Hz
      sinusoidal magnetic field could influence serum melatonin concentration and
      pineal enzymes activities in rats. The effects of both duration and intensity of
      exposure were also looked at. Two groups of Wistar male rats were exposed to 50
      Hz magnetic fields of either 1, 10 or 100 microT. The first group was exposed for
      12 hours and the second for 30 days (18 hours per day). During this time the
      animals were kept under a standard 12:12 light: dark cycle with a temperature of
      25 degrees C and a relative humidity of 45 to 50%. Control (Sham-exposed) animals
      were kept in a similar environment but without exposure to a magnetic field. The
      animals were sacrificed under red dim light. Serum melatonin concentration and
      pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT)
      activities were studied. Long-term exposure to a magnetic field (10 and 100
      microT) significantly depressed the nocturne peak of serum melatonin
      concentration and pineal NAT activity whereas no effect was observed on HIOMT
      activity. Short-term exposure depressed both pineal NAT activity and nocturnal
      serum melatonin concentration but only with the highest intensity used (100
      microT). Our results suggest that sinusoidal magnetic fields alter the production
      of melatonin through an inhibition of pineal NAT activity. Both duration and
      intensity of exposure play an important role in this effect. This work shows
      that, 1) sinusoidal magnetic field depresses NAT activity as static magnetic
      field does whereas HIOMT activity remains unaltered whatever the type of
      experiment and the intensity used, 2) the effect observed is related to both the
      duration of exposure and the intensity of magnetic fields, 3) the sensitivity
      threshold to magnetic fields vary with the duration of exposure which strongly
      suggests a cumulative effect of sinusoidal magnetic fields on pineal function.

PMID- 7564883
TI  - Ginsenosides activate DNA polymerase delta from bovine placenta.
AB  - The activation of a DNA polymerase delta (pol delta) purified from bovine
      placenta by ginsenosides from Panax Ginseng C. A. Meyer has been studied.
      Preincubation of the enzyme with ginsenosides increased the polymerase activity
      2.2-fold in a dose-dependent manner. There was a reproducible decrease in Km, in
      addition to a substantial increase in Vmax, in response to increasing
      concentrations of ginsenosides. Ginsenosides also activated the proofreading
      ability of 3'- to 5'-exonuclease activity associated with DNA pol delta. The
      coordinated activation of both polymerase and exonuclease activities of DNA pol
      delta by ginsenosides is consistent with the view that its polymerase and its
      exonuclease activities residue on the same protein molecule. UV/Vis difference
      spectroscopic studies suggested that the activation of DNA pol delta by
      ginsenosides might be due to the conformational change induced by ginsenosides
      binding.

PMID- 7564884
TI  - 1-Acetyl-7-deacetylforskolin: a potential non-specific inactive analog of
      forskolin for estimation of its specific high-affinity binding and adenylyl
      cyclase stimulation in vitro.
AB  - Labeled and unlabeled 1-acetyl-7-deacetylforskolin and forskolin were synthesized
      by acetylation of 7-deacetylforskolin with labeled and unlabeled acetyl chloride.
      The binding of 1-acetyl[1-acetyl-11C]-7-deacetylforskolin ([11C]1-acetyl-7
      deacetylforskolin) and [7-acetyl-11C]forskolin ([11C]forskolin) to rat brain
      membranes was studied using filtration assay. The [11C]forskolin binding was
      decreased with an increasing load of unlabeled forskolin, whereas [11C]1-acetyl-7
      deacetyl-forskolin binding was always very low, the level of which agreed with
      that of the non-specific binding in forskolin. However, binding of [7-acetyl
      11C]1,9-dideoxyforskolin, which has been used as a non-specific inactive analog
      of forskolin, had a higher binding ratio than that of the non-specific binding of
      forskolin. The binding of [11C]forskolin was not affected by an increased load of
      cold 1-acetyl-7-deacetylforskolin. Forskolin activated adenylyl cyclase (AC) in
      cultured human endothelial cells, whereas 1-acetyl-7-deacetylforskolin did not.
      These data show that the 1-acetyl-7-deacetylforskolin lacks specific binding
      affinity and the ability to stimulate AC, while it has similar physical
      properties with forskolin. The compound 1-acetyl-7-deacetylforskolin would be a
      suitable "non-specific inactive analog" of forskolin with which to estimate its
      specific high-affinity binding capacity and to validate forskolin-specific AC
      stimulation in vitro.

PMID- 7564885
TI  - Effects of thapsigargin, an intracellular CA2+ pump inhibitor, on insulin release
      by rat pancreatic B-cell.
AB  - This is the first report as to the effects of thapsigargin (Tg), an inhibitor of
      intracellular Ca2+ pumps, on insulin release by pancreatic B-cells. Tg does not
      alter basal insulin release by the isolated islets, with 3 mM glucose. However,
      it potentiates high glucose-induced insulin release: potentiation of the first
      phase response is dose-related in a concentration range of 1.3-40 microM. In
      isolated B-cells, Tg causes a minimal rise in basal cytosolic free calcium
      concentration ([Ca2+]i) and eliminates high glucose-induced initial lowering of
      [Ca2+]i. Tg does not alter glucose oxidation by the islets and the islet insulin
      content. An elimination of glucose-induced sequestration of Ca2+ into Tg
      sensitive intracellular pool(s) is considered to be the cause of Tg potentiation
      of glucose effect on insulin release.

PMID- 7564886
TI  - Plasma sialic acid in animal models of diabetes mellitus: evidence for modulation
      of sialic acid concentrations by insulin deficiency.
AB  - An elevated circulating sialic acid concentration is a risk factor for
      cardiovascular disease. Serum sialic acid levels are elevated in NIDDM but not in
      uncomplicated IDDM. To study why sialic acid is increased in some types of
      diabetes, we assayed plasma sialic acid in various animal models of diabetes:
      obese (ob/ob) mice, before and after streptozotocin treatment, neonatal
      streptozotocin-treated (nSTZ) rats, and diabetic BB rats during and after insulin
      treatment. In obese mice, which exhibit moderate hyperglycemia and marked
      hyperinsulinemia, plasma sialic acid was decreased by 45% (fed) and 42% (fasted),
      compared to lean controls. Fasting reduced plasma glucose and insulin but
      increased sialic acid in the obese and lean mice. There was a negative
      correlation (r = -0.84, P < 0.001) between log plasma insulin and sialic acid in
      the lean and obese mice. The plasma sialic acid:globulin ratio was reduced by 35%
      in obese mice vs. lean controls, indicating that there may be altered sialylation
      of glycoproteins in obese mice. Streptozotocin treatment of obese and lean mice
      reduced plasma insulin but increased sialic acid. In nSTZ rats, hyperglycemia was
      associated with mild hypoinsulinemia, but not significantly different from
      control animals, and sialic acid was not altered. In diabetic BB rats, plasma
      glucose rose from a mean of 4.9 to 23.5 mM 48 hr after insulin withdrawal but
      sialic acid did not change. We conclude that an elevated plasma sialic acid level
      is associated with marked insulin deficiency, rather than hyperglycemia per se.
      The magnitude and speed of this change in sialic acid varies between species.

PMID- 7564888
TI  - Abatement of bleomycin-induced pulmonary injury by cell-impermeable inhibitor of
      phospholipase A2.
AB  - The mechanism of bleomycin (Bleo)-induced pulmonary injury is not fully
      understood. Elevated levels of lung phospholipase A2 (PLA2) have been previously
      reported following intratracheal (IT) instillation of Bleo, but the role of this
      enzyme in the pathogenesis of lung injury is not clear. In this pilot study, we
      have evaluated the effect of a cell impermeable inhibitor of PLA2 (CME) on Bleo
      induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a
      single IT instillation of Bleo (1 unit/0.5 ml saline). Three groups of male
      Syrian hamsters were evaluated: 1) BLEO-CME animals received IT Bleo and daily
      intraperitoneal (IP) injections of CME (1 mumole/kg), starting 1 day before IT
      instillation; 2) BLEO-SAL animals--received IT Bleo and IP injections of saline
      and 3) SAL-SAL animals--treated with IT and IP administrations of saline. Animals
      were sacrificed 14 days after IT treatment and lung injury was evaluated
      histologically by a semiquantitative morphologic index and by a differential cell
      count of bronchoalveolar lavage fluid. CME treatment significantly ameliorated
      Bleo-induced lung injury compared to BLEO-SAL animals (P < 0.05). The percentage
      of neutrophiles in bronchoalveolar lavage fluid was reduced from 17.7 +/- 3.2%
      (mean +/- S.E.) in BLEO-SAL group to 7.3 +/- 1.7% in BLEO-CME group (P < 0.05),
      achieving levels comparable to SAL-SAL control animals. These results suggest
      that treatment with an extracellular PLA2 inhibitor-CME abates Bleo-induced
      pulmonary injury. This may indicate an active role of PLA2 in the pathogenesis of
      interstitial pulmonary fibrosis.

PMID- 7564887
TI  - Antagonistic effect of buprenorphine on the antitussive effect of morphine is
      mediated via the activation of mu 1-opioid receptors.
AB  - The effect of buprenorphine on the antitussive effect of morphine was examined in
      mice. Buprenorphine at doses of 0.1, 0.3 and 1 mg/kg given i.p. alone have no
      effects on the % inhibition in the number of capsaicin-induced coughs. However,
      pretreatment with the same doses of buprenorphine for 2 hr significantly
      attenuated the antitussive effect of morphine (3 mg/kg, i.p.). Naloxonazine, a
      selective mu 1-opioid receptor antagonist, had no effect of buprenorphine on
      antitussive effect of morphine. These results suggest that buprenorphine
      antagonizes the antitussive effect of morphine via the activation of mu 1-opioid
      receptors.

PMID- 7564891
TI  - Effect of prenatal malnutrition on release of monoamines from hippocampal slices.
AB  - The effect of prenatal protein malnutrition on release of monoamine
      neurotransmitters, their precursors and metabolites, from hippocampal slices was
      investigated in 15, 30, 90 and 220 days old male rats. The release of dopamine
      and its metabolites, tryptophan, and 5-hydroxyindoleacetic acid from hippocampal
      slices of malnourished rats was greater than release from control slices at all
      ages studied. Malnutrition also significantly increased the release of
      normetanephrine but only in the 220 day age group. Potassium-induced
      depolarization increased release of tyrosine, normetanephrine and 5
      hydroxyindoleacetic acid less from slices of malnourished than from control rats.
      The release of norepinephrine, normetanephrine, serotonin and 5
      hydroxyindoleacetic acid increased significantly with age while the release of
      tyrosine, 3,4-dihydroxyphenylacetic acid and homovanillic acid decreased
      significantly with age. Age was also significantly associated with the
      effectiveness of potassium-induced depolarization in increasing release of
      tyrosine, norepinephrine, normetanephrine, tryptophan, serotonin and 5
      hydroxyindoleacetic acid.

PMID- 7564889
TI  - Comparison of bronchodilator responses to adrenomedullin and proadrenomedullin N
      terminal 20 peptide.
AB  - This study was designed to determine and compare airway responses to synthetic
      human adrenomedullin(AM) and proadrenomedullin N-terminal 20 peptide (PAMP) in
      anesthetized guinea pigs in vivo. 10(-7) M AM and PAMP significantly inhibited
      acetylcholine-and histamine-induced bronchoconstriction. However, this
      significant bronchodilator effect of PAMP lasted about five minutes, which was
      much shorter than that of AM. In addition, the bronchodilator effect of AM is
      approximately 100-fold more potent than PAMP. We demonstrated that PAMP had a
      potent bronchodilator activity, and induced a rapid and short-lasting
      bronchodilation. These findings suggest that AM and PAMP may play important roles
      in airway functions.

PMID- 7564890
TI  - Tyrosine phosphorylation and synapse formation at the neuromuscular junction.
AB  - Protein tyrosine phosphorylation is prevalent throughout the nervous system. It
      has been implicated to play an important role in the development and maintenance
      of neuronal functions. In the past few years significant advances have been made
      in our understanding of the molecular mechanisms of synapse formation and
      synaptic plasticity. Protein tyrosine phosphorylation appears to be important in
      the neuron-induced synthesis of the nicotinic acetylcholine receptor and
      aggregation of synaptic proteins at the neuromuscular junction during
      development. In addition, protein tyrosine phosphorylation may regulate the ion
      channel activity of the nicotinic acetylcholine receptor.

PMID- 7564892
TI  - Thyroid hormone upregulates gene expression, synthesis and release of pro
      epidermal growth factor in adult rat kidney.
AB  - Attempts were made to elucidate whether thyroid hormone upregulates renal pro
      epidermal growth factor (pro-EGF) gene expression, biosynthesis and release in
      adult rats which were rendered hypothyroid. Predominantly pro-EGF was detected in
      renal cortex, whereas pro-EGF and its degraded species were found in urine. We
      demonstrated that T3 increased pro-EGF levels in renal cortex to 2.2 +/- 0.17,
      2.37 +/- 0.19, 2.73 +/- 0.25, and 3.10 +/- 0.45 fold within day 1, 2, 4 and 8,
      respectively following treatment. Immunoreactive EGF, assessed by
      immunohistochemical methods, was confined in the distal convoluted tubule and
      thick ascending limb of Henle. T3 markedly enhanced the density of irEGF in these
      nephrons. T3 augmented the concentration of urinary irEGF to 2.1, 2.2, 2.8 and
      3.6 fold within day 1, 2, 4 and 8 and the abundance of urine pro-EGF to 2.53 +/-
      1.39, 3.8 +/- 0.70, 3.59 +/- 1.48 fold within day 1, 2, 4, respectively.
      Moreover, we employed reverse transcriptase/polymerase chain reaction method to
      analyze relative abundance of pro-EGF mRNA in kidneys of various thyroid states
      and found T3 markedly increased pro-EGF mRNA levels after treatment of 1, 2 and 4
      days. These results indicated that thyroid hormone augmented the gene expression,
      biosynthesis and excretion of pro-EGF in adult rat kidney.

PMID- 7564893
TI  - CCB, a novel specific kappa opioid agonist, which discriminates between opioid
      and sigma 1 recognition sites.
AB  - CCB, 6,11-Dimethyl-1,2,3,4,5,6-hexahydro-3-([2'-methoxycarbonyl-2'-(4-
      chlorophenyl)cyclopropyl]methyl)-2,6-methano-3-benzazocin-8-ol, displays
      specificity and very high affinity for kappa opioid receptor types (Ki = 0.41 +/-
      0.19 nM). In contrast to other kappa opioid agonists, CCB is also selective with
      respect to sigma 1 sites (Ki = 1,050 +/- 55 nM). CCB displays antinociceptive and
      sedative effects in the mouse comparable to those of U50,488H and morphine.
      Naltrexone fully antagonizes these effects. The sedative effects of CCB are
      blocked in mice pretreated with naltrexone or nor-BNI. CCB and U50,488H produce a
      superimposable diuresis in rats. Naltrexone and nor-BNI, both are effective in
      antagonizing the effect. CCB does not produce any stereotyped behavior or ataxia
      in the behavioral assay in doses up to 40 mg/kg s.c. These findings suggest that
      CCB might be a useful tool to investigate the physiological role of kappa opioid
      receptors.

PMID- 7564895
TI  - Circadian dosing time dependency in the forearm skin penetration of methyl and
      hexyl nicotinate.
AB  - The forearm skin penetration of hydrophilic methyl nicotinate (MN) and lipophilic
      hexyl nicotinate (HN) was assessed around the clock. The sixteen healthy women
      (median age: 22 years, weight: 57 kg and height: 162 cm) who volunteered for the
      study were synchronized with a diurnal activity from 07.00h (+/- 1h) to 23.00h
      (+/- 1h.30min) and a nocturnal rest before and during the 48h sojourn in air
      conditioned rooms (26 degrees C +/- 0.5 degrees C). Both HN (0.5% ethanol
      solution) and MN (5% ethanol solution) have a vasodilative effect on dermal
      vessels. The lag time (LT) between the delivery of a fixed volume (10
      microliters) of the agent at the skin surface and the beginning of the
      vasodilatation, detected with a laser-Doppler method, was used to quantify the
      penetration kinetics. Tests were performed every 4h, at fixed clock hours, over a
      span of a 40h. Two types of tests were done with each of the agents: fixed site
      (one site only) and shifted sites (10 different places). Both cosinor and ANOVA
      have been used for statistical analyses. The shortest LT (fastest penetration)
      was located around 04.00h. The longest LT (slowest penetration) occurred during
      the day with a single peak around 13.00h in three of the situations, or two peaks
      (HN with fixed site). A rather large rhythm amplitude (peak-to-trough difference
      larger than 50% of the 24h mean LT) was validated.

PMID- 7564894
TI  - Effects of acute caffeine ingestion and menopause on sulfate homeostasis in
      women.
AB  - Inorganic sulfate is a physiological anion which is utilized in the metabolism of
      both endogenous compounds and xenobiotics. Its homeostasis is maintained
      predominantly by facilitated reabsorptive processes in the kidneys. The
      objectives of the present investigation were to evaluate the effects of
      menopausal status and caffeine ingestion on the serum concentrations and
      clearance of inorganic sulfate. Thirty-nine women who were classified as
      premenopausal, postmenopausal with or without estrogen treatment, and
      postmenopausal with osteoporosis participated in the study. The women were
      studied on two separate occasions following the ingestion of a decaffeinated
      beverage to which 6 mg caffeine/kg lean body mass or no caffeine was added. All
      women were habitual caffeine users (mean ingestion of 588 mg caffeine per day)
      but abstained from all caffeine sources for 2 weeks prior to the control study
      day. Postmenopausal women with estrogen supplementation exhibited significantly
      lower sulfate serum concentrations (0.24 +/- 0.02 mM vs. 0.32 +/- 0.04 mM in
      premenopausal women, mean +/- SD, p < 0.05) and a decreased renal reabsorption of
      sulfate for the control (no caffeine) period. There was no difference in serum
      sulfate or sulfate reabsorption in estrogen supplemented postmenopausal women,
      compared with women not taking estrogen. Postmenopausal women with osteoporosis
      had significantly lower creatinine and sulfate clearances than postmenopausal
      women with estrogen supplementation which may be related to their older age, or
      factors related to the disease process. The 6 mg/kg dose of caffeine caused a
      diuresis, but no change in GFR, as indicated by urine volume and creatinine
      clearance values, respectively. Caffeine administration resulted in an increase
      in the sulfate excretion rate; there was no change in sulfate serum
      concentrations. The results of this investigation indicate that menopause results
      in decreased sulfate serum concentrations that may be the consequence of a
      decreased renal reabsorption of sulfate. Secondly, this investigation
      demonstrated that caffeine ingestion increases the urinary excretion of sulfate,
      an effect that may be related to the diuretic effect of caffeine or due to a
      caffeine-induced alteration in the renal reabsorption of sulfate.

PMID- 7564896
TI  - A mutant strain (LEC) of rat with low degree of zinc-induced hepatic
      metallothionein gene expression.
AB  - A mutant strain (LEC) of rats was found to possess the feature of low degree of
      the zinc-induced hepatic metallothionein (MT) gene expression due to an
      alteration of the transcription factor concerned in the gene expression. Northern
      blot analyses showed that the amount of MT-1 mRNA induced by intraperitoneal zinc
      injection is smaller in LEC mutant rat liver than in normal rat liver, while the
      amount of MT-1 mRNA induced by copper injection is indistinguishable between LEC
      and normal rat livers. Gel retardation assays showed that LEC and normal rat
      livers are different in the nuclear protein which binds to the metal-responsive
      element (MRE) of the MT gene in a zinc-dependent manner, and that the efficiency
      of the zinc-dependent binding of the nuclear protein to the MRE is lower in LEC
      rat liver than in normal rat liver. LEC rat should provide a useful model to
      understand the transcription factor concerned in the MT gene expression by zinc.

PMID- 7564897
TI  - The effects of nicotinamide and glimepiride on diabetes prevention in BB rats.
AB  - Glimepiride is an oral sulfonylurea drug; nicotinamide is an inhibitor of poly
      (ADP-ribose) synthetase and a precursor of NAD. Three studies were carried out to
      determine whether glimepiride and/or nicotinamide could prevent diabetes in BB
      rats. In Study I, we administered glimepiride treatment 200 mg/kg/day orally from
      the 35th to 143rd day of age. The incidence of diabetes in the glimepiride group
      was lower than in the control group (32% vs 55%, p < 0.02). In Study II, the
      treatment period was from the 35th to 147th day of age, and rats received
      glimepiride combined with nicotinamide (500 mg/kg/day IP). The treatment group
      showed a 22% incidence of diabetes compared to 53 in controls (p < 0.03). In
      Study III, nicotinamide treatment alone (1000 mg/kg/day orally) and combined with
      glimepiride were compared to untreated controls. The treatment period was from
      the 35th to 167th day of age. Nicotinamide-treated rats showed a 42% incidence of
      diabetes compared to 60% in controls (p = NS). In the nicotinamide combined with
      glimepiride treatment group, a lower incidence (28%) was observed when compared
      to the controls (60%, p < 0.05). These findings suggest that glimepiride can
      prevent diabetes in BB rats; however, nicotinamide when used in young animals
      shows only a trend to lower the incidence of diabetes, and when combined with
      glimepiride, no significant effect is observed.

PMID- 7564898
TI  - Human neutrophil (PMN) oxygen radical production and the cytoskeleton.
AB  - Electron paramagnetic resonance (EPR) studies were conducted to examine oxygen
      radical generation following PMN activation by N-formyl-1-methionyl-1-leucyl-1
      phenylalanine (fMLP) in the presence or absence of phalloidin and cytochalasin B
      (CB), agents which stabilize or disrupt f-actin, or taxol and colchicine which
      stabilize and disrupt microtubule cytoskeletal structures respectively. PMN
      oxyradical production was monitored using the spin trap 5,5-dimethyl-1-pyrroline
      n-oxide (DMPO). PMN when unstimulated, treated with phalloidin (10(-6)-10(-8)M),
      CB (10(-6)-10(-8)M), taxol (10(-6)-10(-8)M), or colchicine (10(-6)-10(-8)M), did
      not produce a detectable DMPO signal. Stimulation with fMLP (10(-6)M), however,
      resulted in a significant hydroxyl radical signal which was augmented by PMN
      treatment with CB (10(-6)-10(-7)M, p < 0.05) and attenuated following PMN
      treatment with phalloidin (10(-6)-10(-7)M, p < 0.05). Interestingly, colchicine
      treatment (10(-6)-10(-8)M) significantly attenuated fMLP-mediated oxyradical
      production, whereas taxol (10(-6)-10(-7)M) significantly increased PMN oxyradical
      production. These data suggest that stabilization of f-actin and disruption of
      microtubules attenuates the PMN oxidative burst, whereas disruption of f-actin
      and stabilization of microtubules increases radical production. These findings
      suggest cytoskeletal domain-specific contributions to PMN oxidative activity.

PMID- 7564899
TI  - Effect of naltrindole on the development of physical dependence on morphine in
      mice: a behavioral and biochemical study.
AB  - The effect of pretreatment with a delta opioid receptor antagonist, naltrindole
      (NTI), on the development of physical dependence on morphine was investigated in
      mice. Several withdrawal signs, an increase in cortical noradrenaline (NA)
      turnover and a decrease in dopamine (DA) turnover in the limbic forebrain were
      observed following naloxone challenge in morphine-dependent mice. Pretreatment
      with NTI (0.3-5 mg/kg, s.c.) during chronic morphine treatment dose-dependently
      suppressed the behavioral and biochemical changes after withdrawal. The blocking
      effects of NTI suggest that delta opioid receptors may play a significant role in
      modulating the development of physical dependence on morphine.

PMID- 7564900
TI  - Effect of adenosine and adenosine agonists on amylase release from rat pancreatic
      lobules.
AB  - The effects of adenosine on the amylase secretion from rat pancreatic lobules
      have been studied. Adenosine induces a dose-dependent stimulation on amylase
      release, which is maximal at a concentration of 10(-4) M. It has been observed a
      clear inhibition of this secretory action when atropine was added whereas no
      amylase release was seen in isolated acini after adenosine. The effect of
      adenosine is completely blocked by the adenosine receptors antagonist
      theophylline (10(-4) M), but not by dipyridamole (10(-3) M), a drug that inhibits
      the transport of adenosine into the cell. The increase of amylase secretion
      induced by adenosine is inhibited by either the relatively selective A1 receptor
      antagonist PD116,948 (10(-6) M) and by the A2 receptor antagonist PD115,199 (10(
      6) M). Significant increases of amylase release are observed after the relatively
      selective A1 receptor agonist R-PIA (10(-5) M) and after the relatively selective
      A2 receptor agonist NECA (10(-4) M). Finally, the effect of R-PIA is not modified
      by coincubation with PD115,199 and the effect of NECA is not affected by
      coincubation with PD116,948. These results suggest that the action of adenosine
      is mediated through the release of acetylcholine and probably by the simultaneous
      occupation of both A1 and A2 adenosine receptors, whereas the intracellular
      action of adenosine could be discarded.

PMID- 7564901
TI  - Potentiation by ouabain of bradykinin-induced catecholamine secretion and calcium
      influx into cultured bovine adrenal chromaffin cells: evidence for involvement of
      Na+ influx associated with the bradykinin B2-receptor.
AB  - The effect of bradykinin (BK), in the presence of ouabain, an inhibitor of Na(+)
      K+ ATPase, on catecholamine (CA) secretion was studied in cultured bovine adrenal
      chromaffin cells, to determine whether Na+, as well as Ca2+, is involved in BK
      receptor mediated CA secretion. BK (10(-8)-10(-5) M)-induced CA secretion was
      markedly potentiated by addition of ouabain (10(-5) M), was blocked by a BK-B2
      receptor antagonist, and was decreased in Ca(2+)-free medium. BK-induced increase
      in 45Ca2+ influx was also potentiated by addition of ouabain. The cultured cells
      were first incubated with BK for 30 min in Ca(2+)-free medium in the presence or
      absence of ouabain and then stimulated for 15 min with Ca(2+)-medium without BK
      or ouabain. Prior stimulation of the cells, BK induced 22Na+ influx and increased
      Ca(2+)-induced CA secretion and these stimulatory effects of BK were potentiated
      by added ouabain. When the cells were stimulated with BK and ouabain in Na(+)
      free sucrose medium, the Ca(2+)-induced CA secretion was greatly reduced. These
      results indicated that activation of the BK-B2 receptor and inhibition of the Na+
      pump both increase the intracellular Na+ level, resulting in increase in Ca2+
      influx and CA secretion.

PMID- 7564902
TI  - Nitric oxide: its identity and role in blood pressure control.
AB  - In response to biochemical factors like catecholamines, bradykinins, histamine
      and physical factors like shear stress, endothelial cells release a non
      prostanoid factor, called endothelium derived relaxing factor (EDRF), which
      relaxes vascular smooth muscle. Since this discovery in 1980, many additional
      agents have been shown to stimulate release of EDRF from endothelium. Biological
      and chemical evidence has supported the proposal that EDRF is actually nitric
      oxide (NO). Research on the synthesis, inhibition and physiological roles of
      nitric oxide (NO) has led to studies of its involvement in blood pressure
      homeostasis and immune functions.

PMID- 7564904
TI  - Effects of cocaine on leakage of creatine kinase from skeletal muscle: in vitro
      and in vivo studies in mice.
AB  - The mechanism of cocaine-induced rhabdomyolysis and/or muscle damage has not been
      elucidated. To determine if cocaine has a direct effect on muscle, isolated
      soleus and EDL muscles were incubated in the presence of 1 mM and 0.2 mM cocaine
      using a pulse and continuous exposure protocol. The release of creatine kinase
      from the isolated EDL muscle was statistically significant only when muscles were
      exposed to 1 mM cocaine for a period of 30 minutes. These findings suggest that
      cocaine-induced creatine kinase release could be mediated by a direct action on
      the fibers. It is also possible, however, that cocaine-induced muscle damage and
      creatine kinase release may be mediated via an indirect effect. It is possible
      that cocaine's vasoconstrictor effects could lead to muscle damage via an
      ischemia-reperfusion injury leading to free radical formation and lipid
      peroxidation. This study, therefore, also investigated the possibility that
      cocaine-induced cytosolic enzyme release may be mediated via the formation of
      free radicals leading to lipid peroxidation. To test this hypothesis, muscle
      total glutathione levels, a free radical scavenger, and muscle thiobarbituric
      acid reactive substances (TBARS), a measurement of lipid peroxidation, were
      examined following an acute IV cocaine dose in mice. Sedentary BalbC mice were
      injected with cocaine (40 mg/kg) or normal saline via the tail vein. Creatine
      kinase levels in serum and total glutathione and TBARS in liver and muscle were
      determined at 4, 8, and 24 hrs. Serum creatine kinase levels were significantly
      elevated 5-fold, while TBARS were elevated 100% in the gastrocnemius muscle of
      cocaine-treated animals at 4 hrs compared to normal saline controls. However,
      serum creatine kinase levels, total glutathione and TBARS in the gastrocnemius
      muscle were not statistically different at 8 or 12 hrs; or in the liver and
      anterior tibialis muscle at 4, 8, or 24 hrs. The present findings suggests that
      lipid peroxidation may be occurring in skeletal muscle after a single IV cocaine
      dose in mice.

PMID- 7564903
TI  - Ca(+2)-phosphatidylserine-dependent protein kinase C activity in fetal, neonatal
      and adult rabbit lung and isolated lamellar bodies.
AB  - Evidence indicates that Ca(+2)-phosphatidylserine-dependent protein kinase C
      (PKC) is involved in regulation of surfactant secretion. This study was done to
      examine PKC activity in lung as surfactant synthesis and secretion is initiated,
      and at birth and to compare these enzyme levels with those in the adult lung. NZW
      rabbits were used. Fetal and adult lungs were fractionated into subcellular
      compartments including a lamellar body fraction, which represents intracellular
      surfactant. The time course for microsomal enzyme activity was compared between
      24th gestational day and adult rabbit lung. The reactivity appeared similar in
      both fractions. PKC specific activity displayed a prominent peak between the 27th
      and 30th gestational days in total homogenate and lamellar bodies. Specific
      activity was also high in nuclear, mitochondrial and microsomal fractions the day
      prior to birth. Adult levels were similar or higher. Total PKC activity was high
      during late gestation but declined sharply the day prior to birth. A marked
      increase was present on the first postnatal day. In contrast lamellar bodies
      displayed a peak in activity between the 27th and 30th gestational days followed
      by a decline to adult levels. Delipidation of lamellar body fraction indicated
      that the high enzyme activity in this fraction on the 27th gestational day was
      not artifactual. The changes observed in PKC in fetal, neonatal and adult lung
      indicate this enzyme activity changes in lung during the period of onset of
      surfactant synthesis and secretion during late gestation and may be associated
      with lamellar bodies, in 27th gestational day fetal lung.

PMID- 7564906
TI  - Estrogen effects on blood amino acid compartmentation.
AB  - The present paper focuses on the study of blood amino acid compartmentation in
      healthy men (lean and obese) and women, with special emphasis on the estimation
      of the recently described blood-cell adsorbed amino acid pool. The wide range of
      changes found in this pool on comparing different physiological situations may be
      attributable to its proposed characteristic high dynamism on the one hand, but
      also to the influence of other factors such as hormones. Along these lines, the
      sex- and obesity-linked variations found here in human blood led to the
      speculation as to whether these differences could be related to the influence of
      estrogens. This hypothesis was further tested by chronically treating a group of
      male rats with estrone and checking their subsequent blood amino acid compartment
      changes (which yielded a greater difference in the adsorbed pool). From the
      overall results obtained it may be concluded that the higher production of
      estrogens in women and obese men affects amino acid availability to the tissues
      by modulating the blood-cell adsorbed amino acid pool through a mechanism that
      is, at present, unknown.

PMID- 7564905
TI  - Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy
      digestive balance in the rat.
AB  - In the present study, we have assessed the apparent retention of gross energy,
      nitrogen and Ca, Mg, Fe, Zn and Cu in rats receiving a diet supplemented with
      fermentable fructo-oligosaccharides with high and low degree of polymerization.
      Feeding 10% Raftilose (degree of polymerization: 4.8) or 10% Raftiline (degree of
      polymerization: 10) decreased to the same extent (a) the fecal excretion of all
      the minerals, despite an increase in total fecal mass excretion leading to an
      improvement of the absorption of Ca, Mg, Fe and Zn; (b) total gross energy
      absorption; and (c) led to an increase in the faecal excretion and to a decreased
      urinary excretion of nitrogen, suggesting a displacement of part of nitrogen
      excretion towards the large intestine. Feeding fermentable fructo
      oligosaccharides may thus constitute a good way to counteract syndromes resulting
      from hyperammonemia or disturbed Fe, Ca, Mg and Zn homeostasis.

PMID- 7564908
TI  - Novel evidence that beta adrenoceptors of the medial septal area regulate blood
      pressure and electrolyte balance.
AB  - We investigated the participation of the beta-adrenoceptors of the septa area
      (SA) in sodium and potassium excretion and urine flow. The alterations in
      arterial pressure and some renal functions were also investigated. The injection
      of 2.10(-9) to 16.10(-9) M of isoproterenol, through a cannula permanently
      implanted into the SA produced a significant dose-dependent decrease in urinary
      Na+ and K+ excretion and urinary flow. Pretreatment with 16.10(-9) M butoxamine
      antagonized the effect of 4.10(-9) M isoproterenol but pretreatment with 16.10(
      9) M practolol did not abolish the effect of isoproterenol. The beta 2-agonist
      terbutaline and salbutamol (4.10(-9) M when injected intraseptally also caused a
      decrease in urine flow and in renal Na+ and K+ excretion. After injection of
      isoproterenol or salbutamol (4.10(-9) M) into the SA, the arterial pressure,
      glomerular, filtration rate (GFR) and filtered Na+ were reduced while Na+
      fractional reabsorption was increased. The results indicate that the beta 2
      adrenoceptors of the SA play a role in the decrease of Na+, K+ and urine flow and
      this effect may be due to a drop in GFR and filtered Na+ and to the rise in
      tubular Na+ reabsorption.

PMID- 7564907
TI  - Activin and activin receptors in the normal urinary bladder:
      immunohistochemistry, in situ hybridization, and RT-PCR.
AB  - To determine whether rat urinary bladder produces activin-A, a multifunctional
      growth factor in the transforming growth factor beta superfamily (TGF beta), we
      have conducted immunohistochemistry using specific antibodies for activin beta A
      subunit which were raised against a synthetic cyclic fragment of the beta A
      subunit of activin. The mature activin-A molecule was identified at transitional
      epithelial cells, smooth muscle, and endothelial cells. To determine if messenger
      RNAs for the beta A-subunits of activin-A and activin receptors are expressed in
      these cells, both in situ hybridization with specific probes and the reverse
      transcription-polymerase chain reaction (RT-PCR) technique with primers specific
      for the beta A-subunit of activin and activin receptors, respectively, were used.
      Messenger RNA expression of the beta A-subunit of activin-A and activin receptors
      were detected by RT-PCR and localized in the transitional epithelial, smooth
      muscle, and endothelial cells as determined by in situ hybridization. In
      addition, the identity of the cDNA product of RT-PCR was verified with DNA
      sequencing. The localization of mature activin-A protein and its corresponding
      message as well as that of activin receptors to urinary bladder cells suggest
      that activin-A may have an autocrine function in the urinary bladder, perhaps in
      the transitional epithelial, smooth muscle, and endothelial cells themselves.

PMID- 7564909
TI  - Stimulation of alpha-adrenoceptors inhibits cholesterol synthesis in freshly
      isolated human mononuclear leukocytes.
AB  - Specific agonists and antagonists for alpha 1- and alpha 2-adrenoceptors were
      used to determine an alpha-adrenoceptor-mediated action of adrenaline on the rate
      of sterol synthesis from [14C]acetate in freshly isolated human mononuclear
      leukocytes. In the presence of the beta-adrenergic blocker propranolol (1
      microM), adrenaline (100 microM) and noradrenaline (100 microM) suppressed sterol
      synthesis by 36% and 38%, respectively, suggesting an action via alpha
      adrenoceptors. The catecholamine effect could be mimicked by alpha 2-selective
      beta-phenethylamines including alpha-methylnoradrenaline, but not by
      imidazolines. alpha 1-Selective agonists like phenylephrine and methoxamine had
      no effect on the pathway. Accordingly, the effects of adrenaline and the alpha 2
      selective agonist alpha-methylnoradrenaline on sterol synthesis were attenuated
      by the unselective alpha-antagonist phentolamine and the selective alpha 2
      antagonist yohimbine, but not by the alpha 1-antagonist prazosin. The results
      provide evidence that catecholamines can affect sterol synthesis in human
      mononuclear leukocytes by stimulating alpha-adrenoceptors of the alpha 2-subtype.

PMID- 7564910
TI  - Highly-sensitive identification of alpha-fetoprotein mRNA in circulating
      peripheral blood of hepatocellular carcinoma patients.
AB  - In order to capture hepatocellular carcinoma (HCC) cells in circulating
      peripheral blood, we made analysis to see if alpha-fetoprotein (AFP) mRNA exists
      in the peripheral blood obtained from patients with HCC and also, as a control,
      from hepatitis-viral-marker-positive patients without HCC and a healthy
      volunteer. As the number of HCC cells in peripheral blood and the quantity of AFP
      mRNA are expected to be very small, the analysis was performed by the reverse
      transcription followed by an original three-step polymerase chain reaction. By
      this highly-sensitive method, 5 of 7 HCC patients were positive for AFP mRNA.
      These 5 positive patients consisted of three with clinically apparent recurrence,
      one preoperative patient with tumor thrombus in the portal vein and one
      recurrence-free patient who developed clinically detectable recurrence three
      months after this analysis. Neither 4 patients with positive viral markers nor a
      healthy volunteer was positive. The results suggest that detection of AFP mRNA
      from HCC patients' peripheral blood by our highly-sensitive RT-PCR may be a
      practical and powerful tool to diagnose the preoperative spreading of HCC and to
      monitor its recurrence.

PMID- 7564911
TI  - Structure and biosynthesis of novel conjugated polyene fatty acids from the
      marine green alga Anadyomene stellata.
AB  - Novel polyunsaturated fatty acids with four conjugated double bonds were found in
      extracts of the green macroalga, Anadyomene stellata. The isolation of five of
      these with different chain lengths and varying degrees of unsaturation--16:5,
      18:4, 20:5, 20:6, and 22:7--was accomplished by organic extraction followed by a
      combination of vacuum and high-performance liquid chromatography. One of these
      that was a novel substance (22:7) was characterized as 4Z,7Z,9E,11E,13Z,16Z,19Z
      do cosaheptaenoic acid and assigned the trivial name stellaheptaenoic acid. The
      structure of this new compound, isolated as its methyl ester derivative, was
      deduced from detailed nuclear magnetic resonance, gas chromatography/mass
      spectrometry (GC/MS), and other spectroscopic methods. Incubation of a
      chloroplast preparation, isolated from a crude algal homogenate by differential
      centrifugation, with six unsaturated fatty acids (palmitoleic, 6Z,9Z,12Z,15Z
      octadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid, 7Z,10Z,13Z,16Z
      docosatetraenoic acid, and 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoi c acid) resulted
      in substantially increased synthesis of unique tetraene compounds as detected by
      ultraviolet spectrophotometry and tentatively identified by GC/MS.

PMID- 7564912
TI  - Synthesis of E,E-diene hydroperoxides via photoisomerization of protected
      hydroperoxides.
AB  - A general approach to E,E-diene hydroperoxides is described based upon
      photoisomerization of readily available Z,E-diene monoperoxyketals. Protection of
      a Z,E-diene hydroperoxide as the 2-methoxypropyl peroxyketal is followed by
      iodine-mediated photoisomerization to produce a mixture enriched in the E,E
      isomer. After chromatographic purification, deprotection of the peroxyketal with
      mild acid furnishes the E,E-diene hydroperoxide.

PMID- 7564913
TI  - Furan fatty acids determined as oxidation products of conjugated octadecadienoic
      acid.
AB  - The objective of this study was to identify oxidation products of conjugated
      linoleic acid (CLA), a series of octadecadienoic acids with conjugated double
      bonds, which have been reported to have antioxidant and anticarcinogenic
      properties. Reference materials of CLA were oxidized in different concentrations
      of water/methanol; for example, 0.5 g octadecadienoic acid was dissolved in 50 mL
      methanol, and 100 mL water was added; this suspension was heated at 50 degrees C
      and continuously aerated. Aliquots of 5 mL were taken over time, extracted with
      ether, treated with diazomethane and examined by gas chromatography/mass
      spectrometry and/or gas chromatography with flame-ionization detection. Products
      identified included the following furan fatty acids (FFAs): 8,11-epoxy-8,10
      octadecadienoic; 9,12-epoxy-9,11-octadecadienoic; 10,13-epoxy-10,12
      octadecadienoic; and 11,14-epoxy-11,13-octadecadienoic. Conjugated dienes should
      be considered as a possible source of FFAs, and CLA may have products common to
      furans in their overall oxidative scheme.

PMID- 7564914
TI  - Reinvestigation of the antioxidant properties of conjugated linoleic acid.
AB  - Despite repeated suggestions that antioxidant activity of conjugated linoleic
      acid (CLA), a collective of conjugated dienoic isomers of linoleic acid,
      underlies its reported anticarcinogenic and antiatherosclerotic effects, the
      antioxidant properties of CLA remain ill-defined. Therefore, this study was
      undertaken to gain more insight into the mechanism of potential CLA antioxidant
      activity. It was tested whether CLA could protect membranes composed of 1
      palmitoyl-2-linoleoyl phosphatidylcholine (PLPC) from oxidative modification
      under conditions of metal ion-dependent or -independent oxidative stress.
      Progress of oxidation was determined by direct spectrophotometric measurement of
      conjugated diene formation and by gas chromatographic/mass spectrometric analysis
      of fatty acids. The oxidative susceptibility of CLA was higher than that of
      linoleic acid, and comparable to arachidonic acid. When oxidation of PLPC (1.0
      mM) was initiated using the lipid-soluble 2,2'-azobis(2,4-dimethylvaleronitrile)
      or the water-soluble 2,2'-azobis(2-amidinopropane) hydrochloride, the radical
      scavengers vitamin E and butylated hydroxytoluene (BHT) at 0.75 microM
      efficiently inhibited PLPC oxidation, as evident from a clear lag phase. In
      contrast, 0.75 microM CLA did not have any significant effect on PLPC oxidation.
      Inhibition of PLPC oxidation by higher concentrations of CLA appeared due to
      competition, not to an antioxidant effect. When oxidation of PLPC was initiated
      by hydrogen peroxide/Fe2+ (500 microM/0.05-20 microM), both vitamin E (1 microM)
      and ethylene glycol-bis(aminoethyl ether) tetraacetic acid (50 microM)
      efficiently inhibited PLPC oxidation. However, CLA (1-50 microM) did not show a
      clear protective effect under any of the conditions tested. We conclude that CLA,
      under these test conditions, does not act as an efficient radical scavenger in
      any way comparable to vitamin E or BHT. CLA also does not appear to be converted
      into a metal chelator under metal-ion dependent oxidative stress, as had
      previously been suggested. On the basis of our observations, a role for CLA as an
      antioxidant does not seem plausible.

PMID- 7564915
TI  - Studies on the mechanism of the ursodeoxycholic acid-induced increase in hepatic
      low-density lipoprotein binding.
AB  - Previously, we have shown, in golden Syrian hamsters, that chronic feeding of
      ursodeoxycholic acid (UDCA), in contrast to that of its 7 alpha-epimer,
      chenodeoxycholic acid (CDCA), produced a significant increment in hepatic low
      density lipoprotein (LDL) uptake, despite similar suppression of bile acid
      synthesis by both bile acids. Evidence for a direct effect of this bile acid on
      hepatic LDL metabolism was shown in vitro, with isolated hamster hepatocytes,
      suggesting that this effect was unique to UDCA and specific for receptor-mediated
      LDL catabolism. The aim of the present study was to define the cellular
      mechanism(s) associated with this phenomenon, using male golden Syrian hamsters.
      Regardless of chronic exposure of the liver to either UDCA or CDCA, acute
      incubation with UDCA consistently resulted in an increase of LDL binding to
      isolated hepatocytes by 15 to 40%. Furthermore, chronic treatment with either
      UDCA or CDCA did not result in alterations in lipoprotein particle composition.
      Likewise, incubation of hepatocytes with UDCA was not associated with a change of
      the membrane lipid composition. In isolated liver membrane fractions, UDCA
      increased both the maximum number of LDL binding sites and the affinity constant
      for LDL by around 35%, suggesting an interaction of UDCA with the LDL receptor,
      at the plasma membrane level, independent of an effect on receptor cycling. The
      results of the studies support a role for UDCA in the recruitment of cryptic LDL
      receptors from a cellular membrane pool, possibly due to the unique localization
      of UDCA in the plasma membrane lipid bilayer.

PMID- 7564917
TI  - Effect of peroxyl radicals on lecithin/cholesterol acyltransferase activity in
      human plasma.
AB  - The objective of this study was to determine whether subjecting human plasma to
      oxidant stress reduces the activity of lecithin/cholesterol acyltransferase
      (LCAT, EC 2.3.1.43). Plasma was incubated for 4 h with 2.25-45 mM of 2,2'
      azobis(2-amidinopropane)HCl (AAPH), a source of peroxyl radicals. A time- and
      concentration-dependent reduction of LCAT activity occurred, relative to control
      samples incubated in the absence of AAPH. Reduction of LCAT activity was
      disproportionate to elevation of thiobarbituric acid-reactive substances (TBARS)
      in the plasma. Added ascorbate was able to significantly prevent reduction of
      LCAT activity, but this effect was unrelated to blockage of TBARS formation by
      the antioxidant. The results suggest that LCAT activity can be down-modulated by
      oxidant stress, but not necessarily by lipid peroxidation.

PMID- 7564916
TI  - Carbohydrate type and amount alter intravascular processing and catabolism of
      plasma lipoproteins in guinea pigs.
AB  - To test the effects of exchanging dietary complex and simple carbohydrate for fat
      calories on lipoprotein metabolism, guinea pigs were fed two different
      fat/carbohydrate ratios: 2.5:58% (w/w) or 25:29% (w/w) with either sucrose or
      starch as the carbohydrate source. Animals fed high-fat had higher plasma low
      density lipoprotein (LDL) and hepatic cholesterol concentrations than animals fed
      low-fat diets (P < 0.01). The cholesteryl ester content per particle was higher,
      and the number of triacylglycerol (TAG) molecules was lower in very low density
      lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high
      fat/sucrose resulted in higher plasma LDL concentrations than intake of high
      fat/starch, and animals fed low-fat/starch had the highest plasma TAG
      concentrations associated with VLDL particles containing more TAG molecules, as
      well as a TAG-enriched LDL. The activity of plasma lecithin cholesteryl:acyl
      transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart
      lipoprotein lipase (LPL) activity was higher in animals fed high-fat diets.
      Hepatic apoprotein B/E (apo B/E) receptor number (Bmax) was increased 21% with
      low-fat diets (P < 0.01). These results suggest that the hypercholesterolemia
      induced by high-fat and by sucrose intake are associated with a higher plasma
      LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the
      action of LPL, might be more readily converted to LDL through the delipidation
      cascade leading to downregulation of hepatic apo B/E receptors. The
      hypertriglyceridemia associated with low-fat intake may result from increased
      production of VLDL TAG, which would explain the increased TAG content and the
      higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet.

PMID- 7564918
TI  - Kinetic analysis of cardiolipin synthase: a membrane enzyme with two
      glycerophospholipid substrates.
AB  - Mitochondrial cardiolipin synthase catalyzes the transfer of a phosphatidyl
      moiety from phosphatidyl-CMP (PtdCMP) to phosphatidylglycerol (PtdGro) in the
      presence of specific divalent cations. The synthase was solubilized from
      Saccharomyces cerevisiae mitochondria and purified about 300-fold. The partially
      enzyme was part of a medium-size, mixed micelle which had to bind to a foreign
      substrate/detergent micelle before catalysis could occur. The kinetics of
      cardiolipin synthase were studied by changing the molar fraction of substrate in
      the micelles. The enzyme obeyed Michaelis-Menten kinetics in relation to PtdCMP
      with a Km of 0.03 mol%. PtdGro caused sigmoidal kinetics with a low apparent
      affinity. It is speculated that it was involved in docking the enzyme to the
      substrate/detergent micelle. Cardiolipin synthase did not catalyze isotope
      exchange between [14C]CMP and PtdCMP, virtually excluding a ping-pong catalytic
      mechanism. Mg2+ stimulated the activity by increasing the turnover number rather
      than the substrate affinity, a mechanism which was also found for the Co(2+)
      activation of rat liver cardiolipin synthase. It is concluded that a direct
      association of the metal ion and the enzyme forms the active cardiolipin synthase
      which has a very high affinity for PtdCMP and a lower affinity for PtdGro.

PMID- 7564919
TI  - Synergistic induction of phospholipid metabolism by granulocyte-macrophage colony
      stimulating factor and steel factor in human growth factor-dependent cell line,
      M07e.
AB  - Steel factor (SLF), the ligand for the c-kit proto-oncogene tyrosine kinase
      receptor, synergizes with several hematopoietic growth factors to produce greatly
      enhanced proliferation of normal human hematopoietic progenitor cells as well as
      that of the human growth factor-dependent myeloid cell line, M07e. The mechanisms
      of this phenomenon remain unknown. In an attempt to understand the cellular
      processes relevant to this phenomenon, we examined the effects of SLF and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) on induced lipid
      metabolism in M07e cells. We find that both GM-CSF and SLF induced increased
      phosphatidylcholine (PC) turnover rates (biosynthesis and degradation) as
      measured by increased [3H]-choline labelling, with SLF being more potent than GM
      CSF after 6 h of stimulation, but equipotent at 24 h of stimulation. The
      labelling of aqueous intermediates of PC metabolism was also increased by
      cytokine stimulation, most notably phosphocholine. Simultaneous stimulation with
      GM-CSF plus SLF resulted in a true synergistic induction of PC, lysoPC, and
      phosphocholine labelling. GM-CSF and SLF each induced asymmetric labelling of
      various phospholipid classes as measured by incorporation of different [3H]-fatty
      acids. [3H]-myristic acid labelling of phosphatidylserine was most prominently
      induced (approximately 12-fold). Cytosolic choline kinase activity was also
      upregulated more than twofold over control by SLF, which might contribute to the
      increased phosphocholine labelling. These effects may have relevance to the
      intracellular mechanisms of the synergistic proliferative stimulation of SLF plus
      GM-CSF on M07e cells.

PMID- 7564921
TI  - Dietary fatty acids, membrane transport, and oxidative sensitivity in human
      erythrocytes.
AB  - This study examined effects of dietary n-3 fatty acids on age-related changes in
      erythrocyte anion transport and susceptibility to oxidation. Blood was drawn from
      healthy adult volunteers before and after six weeks' supplementation (nine/group)
      with 4.0 g/day of safflower oil (containing 2.9 g n-6 fatty acids) or fish oil
      (containing 1.2 g long-chain n-3 fatty acids). Following density separation of
      young and old erythrocytes, membrane anion transport and cell membrane lipid
      composition were measured. Oxidative damage was measured in erythrocyte ghosts
      exposed to a free radical generator. Fish oil significantly increased 16:0 and
      20:5n-3 in ghosts of both young and old cells, and 22:5n-3 and 22:6n-3 in old
      cells alone. Safflower oil increased 16:0, 18:0, 18:1n-9, and 22:5n-6 in ghosts
      of young cells only. The age-dependent increase in membrane anion transport (P <
      0.01) was decreased by dietary fish oil supplementation, but not by safflower oil
      supplementation. Safflower oil and fish oil increased the susceptibility of both
      young and old erythrocytes to oxidative damage by free radical generation (P <
      0.001).

PMID- 7564920
TI  - Plasma fatty acids and lipids in two separate, but genetically comparable,
      Icelandic populations.
AB  - Levels of serum lipids and lipoproteins, and the fatty acid composition of plasma
      phospholipids, were measured in two genetically comparable, but widely separated,
      populations. The 1975 mortality rates for ischemic heart disease were
      significantly higher in one of these populations, the Manitoban residents of pure
      Icelandic descent, than in the other, a rural population from Northeastern
      Iceland. Two study populations, Icelanders and Icelandic-Canadians, were drawn
      from these larger populations. The study populations were matched for age and sex
      and divided into three age groups, 20-39, 40-59, and 60-69 years. In comparison
      to the Icelandic-Canadians, the Icelanders exhibited significantly higher levels
      of total cholesterol, low-density lipoprotein cholesterol, and high-density
      lipoprotein cholesterol, but lower triglyceride levels. Their plasma
      phospholipids contained significantly lower levels of saturated fatty acids
      (SFA), monounsaturated fatty acids, and n-6 polyunsaturated fatty acids (PUFA);
      but their n-3 PUFA levels were three times as high. It was additionally found
      that fatty acid composition of plasma phospholipids differed among Icelanders of
      different ages. SFA levels were significantly lower, and n-6 PUFA levels
      significantly higher, in the 20-39 year group than in the 60-69 year group,
      possibly due to different dietary fat consumption patterns between generations.
      No corresponding age-related difference in the fatty acid composition of plasma
      phospholipids was found in the Icelandic-Canadian study population. As the
      Icelandic and Icelandic-Canadian groups are assumed to be genetically similar,
      the biochemical differences between them are evidently due to environmental,
      probably dietary, differences. The findings indicate that n-3 PUFA may be
      cardioprotective in the context of an otherwise atherogenic diet.

PMID- 7564922
TI  - Separation of gamma- and alpha-linolenic acid containing triacylglycerols by
      capillary supercritical fluid chromatography.
AB  - The separation of gamma- and alpha-linolenic acid containing triacylglycerols
      with an identical acyl carbon number and degree of unsaturation was obtained on
      capillary supercritical fluid chromatography using a 25% cyanopropyl-75%
      methylpolysiloxane stationary phase. The resolution of 1,3-dioleoyl-2-alpha
      linolenoyl-sn-glycerol was 1.35 on a 10 m x 50 microns i.d. column, whereas the
      resolution was enhanced to 1.66 by combining two 10-meter columns in series. The
      difference in the position of double bonds in one linolenic acid residue of
      triacylglycerols resulted in two series of peaks in the separation of alpine
      currant (Ribes alpinum) and black currant (R. nigrum) seed oils. The use of the
      10-meter column was found to be appropriate for the screening of the
      triacylglycerol profile in both seed oils studied.

PMID- 7564923
TI  - Lymphatic fatty acids from rats fed human milk and formula supplemented with fish
      oil.
AB  - Absorption of long-chain polyunsaturated fatty acids from human milk and formula
      supplemented with fish oil was studied to determine if the distribution route
      into lymphatic triacylglycerol (TAG) and phospholipid (PL) varies with the
      dietary source. Rats were intraduodenally infused with human milk or formula
      containing graded amounts of fish oil (0, 0.5, or 1.0 g/100 mL), and the
      mesenteric lymph was collected. Arachidonic acid (20:4n-6) levels in lymphatic
      TAG and PL were highest from animals fed human milk. In the animals infused with
      formula containing fish oil, as the amount of eicosapentaenoic acid (EPA, 20:5n
      3) infused increased, there was essentially an equal increase in EPA associated
      with both lymphatic TAG and PL. Animals intraduodenally infused with human milk
      or formula without fish oil had only minor levels (less than 1%) of EPA in the
      lymph. In the fish oil-treated animals, as the amount of docosahexaenoic acid
      (DHA, 22:6n-3) infused increased, there was a 16-fold increase in DHA associated
      with lymphatic TAG, but only a 3-fold increase in DHA associated with lymphatic
      PL. The highest level of DHA in rats infused with human milk was observed in
      lymphatic PL. Hence, fish oil can be added to formula as a source of long-chain
      polyunsaturated fatty acids, but the distribution of fatty acids into lymphatic
      TAG and PL is not the same as that observed with human milk.

PMID- 7564924
TI  - Comparison of the fatty acids of the tunicate Botryllus schlosseri from the Black
      Sea with two associated bacterial strains.
AB  - The fatty acid composition of the tunicate Botryllus schlosseri and of two
      bacterial strains found within the tunicate, namely Vibrio parahaemolyticus and
      of an associated but previously unreported gram positive cocci were studied. The
      polyunsaturated fatty acids 6,9,12-octadecatrienoic acid, 5,8,11,14,17
      eicosapentaenoic acid, and 4,7,10,13,16,19-docosahexaenoic acid were particularly
      abundant in B. schlosseri and were not detected in the two bacterial strains
      found in the tunicate. The iso/anteiso pair, 13-methyltetradecanoic acid and 12
      methyltetradecanoic acid, were the principal fatty acids in the gram positive
      cocci, and the 9- and 11-hexadecenoic acids were particularly abundant in V.
      parahaemolyticus. The diunsaturated fatty acid 9,12-octadecadienoic acid was also
      shown to be present in V. parahaemolyticus. The fatty acid composition of a third
      bacterial strain, characterized as either a Pseudomonas or an Alteromonas
      species, and shown to be present only in the sea water from the Black Sea and not
      in B. schlosseri, is also reported. This is the first investigation on fatty
      acids from Black Sea bacteria.

PMID- 7564926
TI  - Residents' breast examination performance. How often? How well?
AB  - The American Cancer Society recommends annual clinical breast examination (CBE)
      for women with average risk of breast cancer beginning at age 40. The purpose of
      the current chart review study was to determine the adequacy of CBE performed by
      house officers in a community teaching hospital. A chart audit of 92 women aged
      50 or older who were consecutively admitted to the medical service was used as a
      baseline measure of CBE documentation. Two subsequent series of 100 women each
      were evaluated. The first series, which also involved women admitted to the
      medical service, followed increased emphasis on the importance of CBE during
      twice daily conferences with supervisor staff. The second series involved women
      admitted to the obstetrics/gynecology service. In that series, house staff used
      two history/physical examination forms: one with a slot dedicated to CBE and one
      without a dedicated slot. Results indicate that supervisors' stressing the
      importance of CBE resulted in only slight improvement in house officers'
      performance, even in the presence of risk factors for breast cancer. In the third
      chart audit, CBE was documented by 88% of house staff who used a form with a
      dedicated slot for CBE; there were no CBE documentations among staff who used a
      form without a dedicated slot. The dedicated form was more successful in
      increasing CBE performance and documentation than verbal emphasis about the
      importance of breast cancer screening.

PMID- 7564925
TI  - Acute outpatient care and comprehensive management of acute myocardial ischemia
      in chest pain emergency departments.

PMID- 7564927
TI  - Solid and papillary epithelial neoplasm diagnosis and treatment: a case study.

PMID- 7564928
TI  - Urinary tract infections in the elderly.

PMID- 7564929
TI  - Aesculapius at the bicentennial: reflections on the evolution of the insignia of
      the Medical and Chirurgical Faculty of Maryland.

PMID- 7564930
TI  - A brief history of women and organized medicine.

PMID- 7564931
TI  - New EMS Palliative Care/DNR protocol will replace existing hospice protocol.

PMID- 7564932
TI  - The role of reluctance to give up life in the measurement of the values of health
      states.
AB  - Questions that involve willingness to risk or give up life often are used to
      measure the values of health states. In the Boston Health Study, interviews with
      291 patients who had AIDS included questions about health status and current
      desire for resuscitation, and a series of hypothetical questions about desire for
      life-extending efforts if the patients found themselves in undesirable states,
      such as being chronically nauseous or blind. An index, "reluctance to give up
      life" was made from five such questions. The desire for resuscitation was related
      to current health status, but the general reluctance to give up life was not.
      Desire to be resuscitated was significantly related to current health status only
      when "reluctance to give up life" was "low." For people reluctant to say they
      will give up any life at all, questions that involve risking or trading life seem
      likely to be poor measures of the values of health states.

PMID- 7564933
TI  - The person-trade-off approach to valuing health care programs.
AB  - The person-trade-off technique is a way of estimating the social values of
      different health care interventions. Basically it consists in asking people how
      many outcomes of one kind they consider equivalent in social value to X outcomes
      of another kind. The paper outlines a number of the author's previous studies
      using the technique. The studies suggest that while the technique is
      theoretically appealing for resource-allocation purposes, it is in practice quite
      demanding. It needs to be applied in fairly large groups of subjects to keep
      random measurement error at an acceptable level. Possible framing effects include
      the effects of argument presentation and the choice of start points in numerical
      exercises. To control for these effects, it seems important to take subjects
      through a multistep procedure, in which they are induced to carefully consider
      the various arguments that might be relevant in each exercise and to reconsider
      initial responses in the light of their implications. The investigator must also
      think through which decision context he or she wishes to study and make his or
      her choice of context very clear when reporting the results. In spite of these
      problems, the person-trade-off technique deserves greater attention in the field
      of cost-utility analysis.

PMID- 7564934
TI  - Assessing preferences about the DNR order: does it depend on how you ask?
AB  - Despite increasing emphasis on advance directives, there has been little
      methodologic work to assess preferences about the "do not resuscitate" (DNR)
      order. This developmental work assessed, in a non-patient group, the performance
      of a probability-trade-off task designed to assess DNR attitudes, in terms of
      framing effects and stability of preferences. 105 female nursing students each
      completed one of two versions of the task. In version I (n = 58), the trade-off
      moved to increasingly negative descriptions of the outcomes of resuscitation
      (decreasing chance of survival and increasing risk of brain death), whereas in
      version II (n = 47), the trade-off moved to increasingly positive descriptions.
      One week later, repeat assessments were obtained for versions I (n = 35) and II
      (n = 28). The DNR preference scores were lower and more stable when the task
      moved to increasingly positive descriptions; perhaps this version of the task
      tends to weaken risk aversion. These results imply that care should be used in
      applying a probability trade-off task to the assessment of DNR preferences, since
      artefactual effects could be induced.

PMID- 7564936
TI  - Probability judgement in medicine: discounting unspecified possibilities.
AB  - Research in cognitive psychology has indicated that alternative descriptions of
      the same event can give rise to different probability judgments. This observation
      has led to the development of a descriptive account, called support theory, which
      assumes that the judged probability of an explicit description of an event (that
      lists specific possibilities) generally exceeds the judged probability of an
      implicit description of the same event (that does not mention specific
      possibilities). To investigate this assumption in medical judgment, the authors
      presented physicians with brief clinical scenarios describing individual patients
      and elicited diagnostic and prognostic probability judgments. The results showed
      that the physicians tended to discount unspecified possibilities, as predicted by
      support theory. The authors suggest that an awareness of the discrepancy between
      intuitive judgments and the laws of chance may provide opportunities for
      improving medical decision making.

PMID- 7564935
TI  - Advance directives: a policy-capturing approach.
AB  - Policy capturing was used to provide insight into those factors that people
      consider important in the decision of whether to accept life-sustaining medical
      treatment. First, open-ended interviews with community-dwelling elderly persons
      (n = 30) were conducted to determine the factors they would consider when
      drafting an advance directive. College students (n = 53) then made judgments as
      to whether they would accept life-sustaining treatment for each of 100
      hypothetical vignettes comprising a similar set of factors. Results revealed that
      1) students made consistent judgments, 2) there was considerable variability in
      their mean judgments, 3) the most influential factors were mental and physical
      functioning, 4) mental and physical functioning had an interactive effect on
      judgments, and 5) subjective estimates of importance were significantly related
      to policy-capturing weights. This approach for studying the relationship of
      individuals' values to their acceptance of life-sustaining therapy may be useful
      in future studies of patient and surrogate decision making.

PMID- 7564937
TI  - Effects of patient education on decisions about breast cancer treatments: a
      preliminary report.
AB  - The authors examined the effects of materials for educating patients about
      treatment options for breast cancer on knowledge about the disease, preferences
      for alternative treatments, and how changes in knowledge and preferences were
      related. Eighty-two undergraduate students acted as advisors to a hypothetical
      patient. They completed a knowledge test and rated their preferences for three
      options--breast-sparing surgery with radiation, mastectomy followed by
      reconstructive surgery, and mastectomy followed by use of a breast prosthesis-
      before and after viewing a videotape or a booklet version of the educational
      materials. Both formats increased knowledge scores. Treatment preferences were
      not affected by reading the booklet, but viewing the videotape resulted in a
      preference shift toward breast-sparing surgery. This media difference may be due
      to features of the video that were not reproduced in the booklet, such as
      interviews with other patients. Knowledge gains were uncorrelated with preference
      changes.

PMID- 7564939
TI  - Confidence intervals for cost-effectiveness ratios.
AB  - The problem of variability in computed cost-effectiveness ratios (CERs) is
      usually addressed by performing sensitivity analyses to determine the effects on
      these ratios of plausible ranges of values of input parameters. However, the
      sampling variation that exists in these estimated parameters can be utilized to
      obtain confidence intervals for cost-effectiveness ratios. As cost-effectiveness
      analysis becomes more widely used, new techniques need to be developed for
      establishing when a difference in strategies evaluated is meaningful. A first
      step is to establish the precision of the CER itself. The authors estimate the
      precision of a CER in the context of a statistical model in which the primary
      outcome is survival, with cost and effectiveness defined in terms of the
      underlying survival distribution (S). Effectiveness (alpha) is measured by life
      expectancy, restricted to a finite time horizon and discounted at a fixed rate r,
      alpha = integral of e-rtS(t)dt. Cumulative cost (beta) per patient is regarded as
      resource utilization and incurred randomly over time depending on the survival
      experience of the patient, beta = integral of e-rtS(t)dC(t), where C(t) is the
      total potential resources utilized up to time t. Average cost-effectiveness (ACE)
      of a single strategy is beta/alpha, and when comparing two strategies, the CER is
      delta beta/delta alpha, the ratio of the incremental cost to the difference in
      mean survival. Utilizing the sampling distribution of the Kaplan-Meier estimate
      of S yields standard errors and confidence intervals for ACE and CER. The
      technique is applied to survival data from 218 previously studied patients to
      assess 95% confidence intervals for the CER and ACE of the implantable
      cardioverter defibrillator as compared with electrophysiology-guided therapy.

PMID- 7564938
TI  - Decision-making strategies for telephone triage in emergency medical services.
AB  - Decision-making strategies used by nurses in telephone triage involving public
      emergency calls for medical help were investigated as a function of task urgency
      and complexity in the real-world dynamic environment. The sample included 34
      nurses as call receivers. Transcripts of 50 nurse-client dialogues and 50
      explanations of the decision-making process, elicited immediately after
      completion of the calls, were analyzed using methods of discourse and protocol
      analyses. In high-urgency situations, heuristic rules based on symptoms were
      used, and the decisions were mostly accurate. With the increase in problem
      complexity, more causal explanations were found, and the decisions were more
      often inaccurate. Furthermore, the explanations supporting the accurate decisions
      were often inaccurate, showing a decoupling of knowledge and action. Alternate
      strategies were used in moderate- to low-urgency conditions, where contextual
      knowledge of the situations was exploited to identify the needs of the clients
      and to negotiate the best plan of action to meet these needs, resulting in more
      accurate decisions.

PMID- 7564940
TI  - Bayesian decision making based on measurements containing errors.
AB  - The paper presents a Bayesian approach to the construction of diagnostic and
      prognostic algorithms, based on the use of several diagnostic factors (tests) in
      combination. With this approach, the simultaneous use of dichotomous, discrete,
      categoric, and continuous factors is easy and the resulting algorithms are more
      efficient than those of other known methods. Moreover, each factor value that is
      available for use is assumed to represent an estimate (the result of an imperfect
      measurement) of some (unknown) true value. The proposed method of accounting for
      measurement errors is advantageous as regards efficiency for users of the
      algorithm (physicians) if the accuracy of the factor-measurement techniques at
      their disposal differs from that of the constructor of the algorithm (the
      scientist). The approach is illustrated by an example, and possible error models
      and methods of collecting statistical data are discussed.

PMID- 7564942
TI  - Measuring patient preferences: rating scale versus standard gamble.

PMID- 7564941
TI  - Testing an underlying assumption on a ROC curve based on rating data.
AB  - The receiver operating characteristic (ROC) curve is widely accepted as the
      measurement that best represents the accuracy of a diagnostic system that
      consists of a diagnostic imaging modality and a reader who is interpreting
      results from the modality. However, there is one implicit assumption in a ROC
      curve: that the cutoff points to declare a positive test for decision variables
      of a diseased patient and a nondiseased patient are the same. If this assumption
      is violated, then a ROC curve does not exist. The author develops a statistical
      procedure to test this assumption. To demonstrate, he applies the method to a ROC
      data set and shows that the assumption of the equal cutoff points could be
      rejected.

PMID- 7564943
TI  - Assessing patients' preferences.

PMID- 7564944
TI  - Utility measurement and the allocation of health care resources.

PMID- 7564945
TI  - Validity of diagnostic scoring models for gastrointestinal disease.

PMID- 7564947
TI  - MNA takes firm stand on medication administration.

PMID- 7564946
TI  - Computer graphics for Bayes calculations.

PMID- 7564948
TI  - In the child's best interest.

PMID- 7564949
TI  - MNA nurses week health fair a resounding success.

PMID- 7564951
TI  - HIV testing during pregnancy: implications for prenatal nurses.

PMID- 7564950
TI  - Myths and realities of the BCG vaccine in the pediatric population.

PMID- 7564952
TI  - Health problems facing homeless children.

PMID- 7564953
TI  - 6,000 unlicensed persons certified to administer medications.

PMID- 7564954
TI  - Ethics column.

PMID- 7564955
TI  - Nurses key to legislation for improved childbirth and postpartum care benefits.

PMID- 7564956
TI  - Academic little league.

PMID- 7564957
TI  - Alan Turing: the machine, the enigma, and the test.

PMID- 7564958
TI  - Patient handouts from the internet.

PMID- 7564959
TI  - Oxymorons.

PMID- 7564960
TI  - Measurement of intelligence: misplaced trust and the lure of prophecy.
AB  - A careful look at studies of "intelligence" and "aptitude" tests belies the
      contention that these tests measure heritable attributes. Rather, they are
      achievement tests that measure learned abilities. When stripped of the aura of
      "intelligence" and "aptitude" and compared with other indexes of accomplishment,
      they are poor predictors of future performance. Furthermore, when promulgated as
      measures of cognitive potential, they are socially harmful, particularly to
      disadvantaged children.

PMID- 7564961
TI  - Current status of interactive multimedia education in medicine.
AB  - This article describes a subset of interactive medical education software that is
      representative of currently available products. Packages are now being produced
      with a variety of languages and "authoring" programs and have been distributed
      over CD-ROMs, floppy disks, and laser videodiscs. The developers and distributors
      include individuals, universities, pharmaceutical companies, publishers, and
      software companies. The target audiences are physicians, allied health workers,
      patients, and students. Software development is currently being encouraged by the
      recognition, on the part of several professional organizations, of the need to
      use computers in medical education.

PMID- 7564962
TI  - Clinical computing: a view from the United Kingdom.

PMID- 7564963
TI  - Lecture to the London Mathematical Society on 20 February 1947. 1986.

PMID- 7564964
TI  - Physicians' online: a free version of Medline.

PMID- 7564965
TI  - MedHelp: a Windows system offering drug information and selection.

PMID- 7564966
TI  - Exercise-induced gastric mucosal acidosis.
AB  - Gastric acidosis as assessed by tonometry was applied to evaluate changes in
      splanchnic blood flow during exercise. In six healthy male oarsmen, we determined
      gastric acidosis in response to 30 min of maximal ergometer rowing. The gastric
      mucosa carbon dioxide tension was determined by equilibration of isotonic saline
      to the tonometer. Arterial bicarbonate (HCO3-), pH, arterial oxygen tension
      (PaO2), and saturation (SaO2) were obtained simultaneously, while pH (pHi) of the
      gastric mucosa was calculated using the Henderson-Hasselbach equation. During
      rowing PaO2 and SaO2 decreased to values of 73.7 mm Hg and 95.5%, respectively (P
      < 0.05). However, during the last minute of rowing the values were normalized
      with a hyperventilation reducing PaCO2 to 27.1 mm Hg (P < 0.05). Rowing decreased
      HCO3- from 25.8 (21.4-28.5) to 14.1 (11.6-17.4) mmol l-1, while the gastric
      carbon dioxide tension increased from 36.8 (24.1-63.9) to 61.7 (48.9-82.0) mm Hg
      (P < 0.05). Accordingly, pHi decreased from 7.25 (7.04-7.48) to 6.79 (6.67-6.85)
      (P < 0.05). Arterial pH also decreased (from 7.42 (7.41-7.44) to 7.29 (7.26-7.33)
      (P < 0.05)), with the enlarged difference between pH and pHi suggesting marked
      splanchnic hypoperfusion during rowing.

PMID- 7564967
TI  - Maximal and ventilatory threshold responses to treadmill and water immersion
      running.
AB  - This study compared the metabolic responses of 13 endurance runners, familiar
      with nonweight-bearing water immersion (WI) running, at ventilatory threshold
      (Tvent) and maximal effort (VO2max) for both treadmill and WI running
      performance. Oxygen consumption (VO2), ventilation (VE), heart-rate (HR), VE/VO2,
      respiratory exchange ratio (RER), perceived exertion (RPE), and stride frequency
      (SF) were measured at Tvent and VO2max. Paired t-tests revealed higher VO2max
      (59.7 vs 54.6 ml.kg.-1min-1), HRmax (190 vs 175 bpm), RERmax (1.20 vs 1.10), VO2
      at Tvent (46.3 vs 42.8 ml.kg.-1min-1), HR at Tvent (165 vs 152 bpm) for treadmill
      versus WI running, respectively. Treadmill and WI VEmax (109.0 vs 105.8 l.min-1),
      RPEmax (20), VE at Tvent (66.4 vs 65.7 l.min-1), RER at Tvent (0.99 vs 0.98), RPE
      at Tvent (13 vs 12) were similar, as were blood lactate [BLa] values obtained at
      30 s (10.4 vs 9.8 mmol.l-1) and 5 min (9.7 vs 9.2 mmol.l-1) post-test. SF values
      over time were higher on the treadmill. The lower WI VO2max with similar peak
      [BLa] and lower SF values suggests that the active musculature and muscle
      recruitment patterns differ in WI running due to the high viscosity friction of
      water, and the nonweight-bearing nature of WI running.

PMID- 7564968
TI  - Thermal responses to swimming in three water temperatures: influence of a wet
      suit.
AB  - The primary objective of this investigation was to determine the thermal and
      metabolic effects of wearing a rubberized wet suit (WS) while swimming for 30 min
      in 20.1, 22.7, and 25.6 degrees C water. Metabolic and body temperature
      measurements were recorded in each water temperature with subjects wearing either
      a WS or a competitive swimming suit (SS). Immediately after each swim the
      subjects cycled for 15 min on a stationary cycle ergometer. Energy expenditure
      (VO2), heart rate, post-swim blood lactate, work completed on the cycle
      ergometer, and rating of perceived exertion (RPE) were similar in all trials.
      Mean (+/- SE) core temperature (Tc) during swimming in the SS trials increased
      0.56 (+/- 0.33), 0.48 (+/- 0.20), and 1.22 (+/- 0.24) degrees C, whereas in the
      WS trial Tc rose 0.62 (+/- 0.22), 1.02 (+/- 0.15), and 0.89 (+/- 0.13) degrees C
      in the 20.1, 22.7, and 25.6 degrees C treatments, respectively. Following
      swimming many of the subjects experienced a decrease in Tc, but it was
      significantly elevated above preimmersion by the end of cycling in all trials
      except the SS 20.1 degrees C trial. Mean trunk temperatures (Ttr) during swimming
      in the WS trials were 4.32 +/- 0.16 (20.1 degrees C), 3.90 +/- 0.25 (22.7 degrees
      C), and 3.21 +/- 0.20 (25.6 degrees C) degrees C warmer than in the SS. Ttr rose
      after the subjects exited the water, but remained significantly below baseline
      throughout cycling in all trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564969
TI  - Inflammatory cell response to acute muscle injury.
AB  - Nonmuscle cells play central roles in muscle repair and regeneration during the
      inflammation that follows muscle injury, although many aspects of the mechanisms
      by which inflammatory cells are attracted to injury sites and activated are
      unknown. Current evidence indicates that substances released from injured muscle
      can act as "wound hormones" that initiate inflammation. Most evidence supports
      the view that mononucleated cells that normally reside in muscle are activated by
      the injury, and then provide the chemotactic signal to circulating inflammatory
      cells. Three subsequent stages of inflammation can be identified, according to
      differences in the populations of inflammatory cells. First, neutrophils rapidly
      invade the injury site and promote inflammation by releasing cytokines that can
      attract and activate additional inflammatory cells. In at least some muscle
      injuries, neutrophils may further damage the injured muscle by releasing oxygen
      free radicals that can damage cell membranes. Next, there is an increase in
      macrophages that invade damaged muscle fibers and phagocytose debris. Finally,
      there is an increase in a second subpopulation of macrophages that are associated
      with muscle regeneration. Although many of the potential mediators that underlie
      the proliferation, invasion, and activation of these inflammatory cell
      populations are known, few have been demonstrated conclusively to function in
      injured muscle in vivo.

PMID- 7564970
TI  - The level and tempo of children's physical activities: an observational study.
AB  - We develop an observation system that quantifies the duration, intensity, and
      frequency of children's physical activities. We use this system to assess the
      level and tempo of energy expenditure under free-ranging, natural conditions
      experienced by 15 children aged 6-10 yr in southern California. Observations were
      recorded every 3 s during 4-h time blocks from 8:00 a.m.-8:00 p.m. Agreement
      among observers using the coding system was 91%. Using indirect calorimetry,
      calibration studies in the laboratory determined VO2 (ml.min-1.min-1) during each
      coded activity, and activities were categorized by intensity (low, medium, or
      high). Subjects were found to engage in activities of low intensity 77.1% of time
      and activities of high intensity 3.1% of time. The median duration of low and
      medium intensity activities was 6 s, of high intensity activities only 3 s with
      95% lasting less than 15 s. Children engaged in very short bursts of intense
      physical activity interspersed with varying intervals of low and moderate
      intensity. These findings may be important for discovering how children's
      activity patterns under natural conditions influence physiological processes
      leading to growth and development. This study demonstrates the advantages of
      using an observational system that captures more than the intensity and frequency
      of children's activities to include duration and the length of intervals between
      activities of varying intensity.

PMID- 7564971
TI  - Variability and tracking of physical activity over 2 yr in young children.
AB  - The purpose of this study was to examine tracking of physical activity at home
      and recess in young children. Three hundred fifty-one Mexican-American and Anglo
      American children entered the study (mean age = 4.4 yr), and 83% completed 2 yr
      of measurement. Physical activity was directly observed on 10 d over 2 yr.
      Measurement waves occurred every 6 months, and each wave consisted of 2 d of
      observation within 1 wk. Children were observed for 60 min at home on a weekday
      evening and up to 30 min during recess at preschool or school. Maximum likelihood
      procedures using a linear mixed-effects model indicated that most of the variance
      in home and recess physical activity was accounted for by short-term/weekly
      factors. Tracking of physical activity accounted for 15% of the total variance at
      home and 8% at recess. Pearson correlations for physical activity over time were
      higher at home than at recess. Tracking of home physical activity was r = 0.15
      when single days were correlated and r = 0.36 when the means of 4 d were
      correlated. There was a small, but detectable, stable component of physical
      activity in young children, at least at home.

PMID- 7564972
TI  - Cardiovascular responses to exercise in sprinters and distance runners.
AB  - The purpose of this study was to examine the cardiovascular responses of
      sprinters and distance runners to isometric (IE) and dynamic exercise (DE).
      Normotensive males were selected and grouped according to prior running
      performance: sprinter (N = 6) or distance runner (N = 6). Each subject completed
      an incremental DE (cycle ergometry) test (6-min stages) at 20%, 40%, and 60% of
      VO2peak, and 3 min of isometric handgrip at 30% of MVC. Blood pressure (BP),
      heart rate (HR), cardiac output (Q), oxygen uptake, and blood lactate were
      measured, while mean arterial blood pressure (MABP), cardiac index (CI), and
      systemic vascular resistance (SVR) were calculated during each stage of DE. BP
      and HR were measured during each minute of IE. Muscle biopsies of the vastus
      lateralis revealed a significant difference in capillary density (capillaries per
      mm2 and capillaries per fiber) between the sprinters and distance runners (323 +/
      23 vs 409 +/- 27 and 2.2 +/- 0.2 vs 3.2 +/- 0.3, P < 0.05) and for the
      percentage of Type I fibers (46.4 +/- 4% vs 64.8 +/- 7%, P < 0.05). The IE
      challenge elicited a greater BP response at minute 3 in the sprinters, which was
      associated with a greater HR response. During DE, there were no significant
      differences in BP or HR between the groups. However, at 60% of VO2peak, the
      distance runners had a significantly higher cardiac index and a lower systemic
      vascular resistance than the sprinters (P < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7564973
TI  - Physiological and performance responses to nicotinic-acid ingestion during
      exercise.
AB  - The purpose of this study was to assess how selected physiological and
      performance responses are affected when the normal increase in plasma free fatty
      acid concentration during exercise is blunted by ingesting nicotinic acid. On
      four occasions, 10 subjects cycled at 68 +/- 1% VO2peak for 120 min followed by a
      timed 3.5-mile performance task. Every 15 min during exercise, subjects ingested
      3.5 ml.kg LBM-1 of one of four beverages: 1) water placebo (WP), 2) WP + 280 mg
      nicotinic acid.l-1 (WP + NA), 3) 6% carbohydrate-electrolyte beverage (CE), and
      4) CE + NA. Ingestion of nicotinic acid (WP + NA and CE + NA) blunted the rise in
      FFA associated with WP and CE; in fact, NA ingestion effectively prevented FFA
      from rising above rest values. The low FFA levels with NA feeding were associated
      with a 3- to 6-fold increase in concentrations of human growth hormone throughout
      exercise. The mean performance time for CE (10.7 min) was significantly less than
      for WP (12.2 min) and WP + NA (12.8 min), but did not differ from CE + NA (11.4
      min). The results indicate that blunting the normal rise in FFA alters the
      hormonal response to exercise and reduces the capacity to perform high-intensity
      exercise.

PMID- 7564974
TI  - Overtraining following intensified training with normal muscle glycogen.
AB  - The purpose of this study was to determine if consumption of appropriate amounts
      of carbohydrate during a period of increased exercise training would protect the
      athletes from becoming overtrained. Eight male competitive cyclists were
      monitored and tested during three training periods: a) normal training (moderate
      intensity, long duration, 7 d, NORM); b) overtraining (high intensity training,
      15 d, OVER); and c) recovery (minimal training, 6 d, REC). Throughout the
      training 160 g of liquid carbohydrate were consumed within the first 2 h after
      the daily exercise bout. Mean dietary intake (NORM = 13.7 +/- 1.6, OVER = 14.1 +/
      1.0 MJ.d-1) and carbohydrate percent (NORM = 64.0 +/- 2.1, OVER = 67.4 +/- 2.5%)
      were not different during the different training periods. Similarly, resting
      muscle glycogen levels were not different (NORM = 530.9 +/- 42.5, OVER = 571.2 +/
      27.5 mumol.g-1 dry weight). Five criteria were used to determine if overtraining
      occurred in a subject (decreased maximal workload, maximal heart rate, ratio of
      maximal lactate to rating of perceived exertion (HLa:RPE), and resting plasma
      cortisol levels, increased affirmative response to a daily questionnaire). All
      subjects met at least three of the five criteria and thus were classified as
      overtrained. Therefore, short-term overtraining may occur even when resting
      muscle glycogen levels are maintained.

PMID- 7564975
TI  - Field trial of a three-dimensional activity monitor: comparison with self report.
AB  - We examined the ability of the Tritrac-R3D to estimate daily energy expenditure
      (EE) and characterize the physical activity patterns of free-living humans. Daily
      EE was estimated by the Tritrac, a 3-d physical activity log (PAL), and a 7-d
      recall (SDR). Digital storage of activity data by the Tritrac allowed us to
      tabulate the number of minutes the monitor recorded EE at specific activity
      intensities. Twenty-five men and women (mean age and body mass 26.7 yr, 72.5 kg)
      wore the monitor for 7 d. The Tritrac significantly underestimated daily EE
      compared with the PAL and SDR, 2552.7 vs 2915.5 kcal.d-1 and 2530.0 vs 2840.3
      kcal.d-1, respectively (both, P < 0.01). Correlations between the Tritrac and PAL
      and the SDR were r = 0.82 and r = 0.77 (both, P < 0.001). Compared with the PAL,
      the Tritrac overestimated time accumulated in sedentary activities (862.7 vs
      827.2 min.d-1) but underestimated time accumulated in active behaviors (37.5 vs
      78.0 min.d-1). In conclusion, these data suggest the Tritrac ranks activity
      levels similarly to the PAL and SDR but it significantly underestimates free
      living energy expenditure.

PMID- 7564976
TI  - Military body fat standards and equations applied to middle-aged women.
AB  - Military circumference equations are used to assess compliance of military
      personnel with body fat (BF) standards. The purpose of the present study was to
      determine the ability of military equations to correctly classify 62 women aged
      40-60 yr (50.9 +/- 6.2, mean +/- SD) as overfat or underfat using underwater
      weighing (UWW) as the reference method and military BF standards as diagnostic
      cutoffs. Values for the mean +/- SD percent BF from UWW, Army, Marine Corps, and
      Navy equations were 29.5 +/- 7.1, 27.3 +/- 4.7, 25.7 +/- 5.8, and 30.3 +/- 5.1,
      respectively. The Army and Marine Corps equations underpredicted percent BF
      compared to UWW, P < 0.05. Bland-Altman plots showed a lack of agreement in
      predicting percent BF in women 40-60 yr between equation and UWW-derived percent
      BF. This finding was supported by the low agreement in correctly classifying an
      individual as meeting or exceeding the BF standards, range 25%-57%, Cohen's
      kappa. The low sensitivities (range 20%-74%) and higher specificities (range 80%
      98%) of the equations indicated they identified individuals who met the BF
      standards better than those who exceeded them. Caution must be exercised when
      using military prediction equations to assess compliance with military BF
      standards in healthy middle-aged women.

PMID- 7564977
TI  - Effect of swimming suit design on the energy demands of swimming.
AB  - Eight competitive male swimmers completed a standardized 365.8 m (400 yd)
      freestyle swimming trial at a fixed pace (approximately 90% of maximal effort)
      while wearing a torso swim suit (TOR) or a standard racing suit (STD). Oxygen
      uptake (VO2), blood lactate, heart rate (HR), and distance per stroke (DPS)
      measurements were obtained. In addition, a video-computer system was used to
      collect velocity data during a prone underwater glide following a maximal leg
      push-off from the side of the pool while wearing the TOR and STD suits. These
      data were used to calculate the total distance covered during the glides. VO2
      (3.76 +/- 0.16 vs 3.92 +/- 0.18 l.min-1) and lactate (8.08 +/- 0.53 vs, 9.66 +/-
      0.66 mM) were significantly (P < 0.05) lower during the TOR trial than the STD
      trial. HR was not different (P > 0.05) between the TOR (170.1 +/- 5.1 b.min-1)
      and STD (173.5 +/- 5.7 b.min-1) trials. DPS was significantly greater during the
      TOR (2.70 +/- 0.066 m.stroke-1) versus STD (2.58 +/- 0.054 m.stroke-1) trial. A
      significantly greater total distance was covered during the prone glide while
      wearing the TOR (2.05 +/- 0.067 m) compared to the STD (2.00 +/- 0.080 m) suit.
      These findings demonstrate that a specially designed torso suit reduces the
      energy demand of swimming compared to a standard racing suit which may be due to
      a reduction in body drag.

PMID- 7564978
TI  - Air friction and rolling resistance during cycling.
AB  - To calculate the power output during actual cycling, the air friction force Fa
      and rolling resistance Fr have to be known. Instead of wind tunnel experiments or
      towing experiments at steady speed, in this study these friction forces were
      measured by coasting down experiments. Towing experiments at constant
      acceleration (increasing velocity) were also done for comparison. From the
      equation of motion, the velocity-time curve v(t) was obtained. Curve-fitting
      procedures on experimental data of the velocity v yielded values of the rolling
      resistance force Fr and of the air friction coefficient k = Fa/v2. For the
      coasting down experiments, the group mean values per body mass m (N = 7) were km
      = k/m = (2.15 +/- 0.32) x 10(-3)m-1 and ar = Fr/m = (3.76 +/- 0.18) x 10(-2)ms-2,
      close to other values from the literature. The curves in the phase plane
      (velocity vs acceleration) and the small residual sum of squares indicated the
      validity of the theory. The towing experiments were not congruent with the
      coasting down experiments. Higher values of the air friction were found, probably
      due to turbulence of the air.

PMID- 7564980
TI  - Scaling anaerobic performance for differences in body dimensions.

PMID- 7564979
TI  - The validity of non-exercise cardiorespiratory fitness prediction models.

PMID- 7564982
TI  - Effects of oral contraceptives on fibrinolytic response to exercise.
AB  - In this study the influence of low-dose oral contraceptives (OC) on the different
      components of the fibrinolytic system before and immediately after maximal
      exercise was examined in a group of 18 moderately active women. Nine women using
      OC and nine control women performed a maximal effort treadmill protocol.
      Comparison of the resting parameters revealed higher plasma FbDP, plasminogen,
      alpha 2-antiplasmin and protein C concentrations, and lower PAI activity in the
      OC group. No differences were observed in plasma concentrations of t-PA antigen,
      t-PA activity, PAI antigen, antithrombin III, and protein S. Acute maximal
      exercise resulted in significant increases in t-PA antigen, t-PA activity, t
      PA/PAI complexes, and FbDP in both groups of subjects, while PAI activity was
      reduced. No significant differences were found for the change in those parameters
      between control and OC users. Exercise induced no variation in any of the groups
      for PAI antigen, alpha 2-antiplasmin, plasminogen, protein C, or protein S. Our
      data suggest that changes in the fibrinolytic system induced by physical exercise
      are not affected by oral contraceptives.

PMID- 7564981
TI  - Etiology of iliotibial band friction syndrome in distance runners.
AB  - The objectives of our study were: 1) to examine differences between a noninjured
      cohort of runners (N = 70) and runners afflicted with iliotibial band friction
      syndrome (ITBFS) (N = 56) according to selected anthropometric, biomechanical,
      muscular strength, and training measures; 2) to explore multivariate
      relationships among these measures in both the well and injured groups; and 3) to
      develop specific hypotheses concerning risk factors for injury that will later be
      tested in a prospective observational study. High speed videography (200 fps), a
      force platform (500 Hz), and a Cybex II+ isokinetic dynamometer were used to
      assess rearfoot motion, ground reaction forces, and knee muscular strength and
      endurance, respectively. A linear discriminant function analysis of the training
      data revealed weekly mileage, training pace, number of months using current
      training protocol, % time spent swimming, and % time spent running on a track to
      be significant (P < 0.10). Height was a significant anthropometric discriminator,
      while seven isokinetic strength and endurance measures were found to discriminate
      significantly between the groups. Calcaneal to vertical touchdown angle, and
      maximum supination velocity were significant rearfoot movement discriminators.
      Maximum braking force was the only significant kinetic discriminator. A combined
      discriminant analysis using those variables found to be significant in the
      previous analyses revealed weekly mileage, and maximum normalized braking force
      to be the best discriminators (model P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7564983
TI  - Muscle strength and body composition: associations with bone density in older
      subjects.
AB  - This study investigated the relationship between isokinetic muscle strength and
      bone density (SPA and DPA) in men and women aged 45-77 yr. Regression models were
      adjusted for age, weight, smoking status, and calcium supplementation. Elbow
      extensors (but not flexors) peak torque was correlated with radial density in men
      (partial r = 0.26, P < 0.05) and women (partial r = 0.24, P < 0.05). Knee flexor
      (but not extensor) peak torque in women was significantly correlated with spine
      density (partial r = 0.28, P < 0.05), and muscle mass was significantly
      correlated with Ward's triangle density (partial r = 0.35, P < 0.05). No
      associations between knee flexor or extensor muscle strength and spine or femur
      bone density were observed in men. Fat-free mass (FFM, hydrodensitometry) was
      associated with all bone density sites in males and females (partial r = 0.30
      0.55; P < 0.05). These results demonstrate that 1) significant associations
      observed between elbow extensor strength and radial bone density in men and women
      may reflect loading along the longitudinal axis of the radius associated with
      elbow extensor activity; and 2) significant associations exist between knee
      flexor muscle strength and lumbar density in women only. Additionally, the
      associations between FFM and bone density do not necessarily reflect associations
      between isokinetic muscle strength and bone density.

PMID- 7564984
TI  - The therapeutic role of exercise in patients with orthotopic heart transplant.
AB  - January 1995 marked the 27th anniversary of the performance of the first human
      cardiac transplant in the United States. This followed nearly a decade of
      laboratory work developing and validating the technique involved. During the past
      26 yr, cardiac transplantation has evolved from what was initially considered a
      radical and experimental form of therapy to one that is currently viewed in most
      of the world as a valid form of advanced therapy for end-stage heart disease.
      Today, many patients go home to medical personnel who may not be familiar with
      all the medical parameters associated with a patient's condition after cardiac
      transplantation. If patients with a heart transplant are to live in the community
      and work and enjoy themselves, their ability to lead healthy and active lives
      needs to be recognized and facilitated by professionals in the field of cardiac
      rehabilitation. The purpose of this article is to review the clinical
      considerations related to the physiology of the transplanted human heart. A
      review of studies conducted to investigate the acute and chronic responses to
      exercise in the transplanted human heart is presented. Recommendations for
      exercise testing, exercise prescription, and exercise programming for this
      patient population based on current data are presented.

PMID- 7564985
TI  - Immune function in marathon runners versus sedentary controls.
AB  - Marathon runners (N = 22) who had completed at least seven marathons (X +/- SEM =
      23.6 +/- 5.7) and had been training for marathon race events for at least 4 yr
      (12.3 +/- 1.3) were compared with sedentary controls (N = 18). Although the two
      groups were of similar age (38.7 +/- 1.5 and 43.9 +/- 2.2 yr, respectively) and
      height, the marathon runners were significantly leaner and possessed a VO2max 60%
      higher than that of the controls. Neutrophil counts tended to be lower in the
      group of marathoners, while other leukocyte and lymphocyte subsets were similar
      to controls. Mitogen-induced lymphocyte proliferation did not differ between
      groups. Natural killer cell cytotoxic activity (NKCA) was significantly higher in
      the marathoners versus controls (373 +/- 38 vs 237 +/- 41 total lytic units,
      respectively, a 57% difference, P = 0.02). For all subjects combined (N = 40) and
      within the group of marathon runners (N = 22), percent body fat was negatively
      correlated with NKCA (r = -0.48, P = 0.002; r = -0.49, P = 0.019, respectively),
      and age was negatively correlated with Con A-induced lymphocyte proliferation (r
      = -0.41, P = 0.009; r = -0.53, P = 0.011, respectively). These data indicate that
      NKCA but not mitogen-induced lymphocyte proliferation is higher in marathon
      runners relative to sedentary controls.

PMID- 7564986
TI  - Cardiac adrenergic responses and electrophysiology during ischemia: effect of
      exercise.
AB  - Whether exercise protects the myocardium from arrhythmias during ischemia (ISC)
      or alters electrophysiology is controversial. We used microelectrode techniques
      in isolated cardiac fibers from exercise-trained (ET: 8-10 wk daily exercise) and
      sedentary (SED: 8-10 wk cage-rest) dogs to examine the effect of exercise on
      cellular electrophysiology during simulated ISC. We superfused fibers first with
      normal Tyrode's, then "ischemic Tyrode's" ([K+]o = 10 mM, pH = 6.7, pO2 < 25 mm
      Hg), and then again with normal Tyrode's. In automatic fibers, maximum diastolic
      potential in normal Tyrode's was -98 +/- 1 mV (ET, N = 22) and -97 +/- 1 mV (SED,
      N = 23); rates were 20 +/- 2 and 18 +/- 3 bpm for ET and SED, respectively. All
      fibers depolarized to -61 +/- 2 mV with ISC. Abnormal rhythms (abnormal
      automaticity with or without delayed afterdepolarizations) during ISC alone were
      seen in 0% of ET and 33% of SED; during ISC with alpha-adrenergic stimulation
      with 5 x 10(-8) M phenylephrine the incidence was 25% of ET and 0% of SED; during
      ISC with isoproterenol it was 75% for ET (P < 0.05 vs control) and 38% for SED.
      Transmembrane potentials in paced subendocardial fibers were similar for ET and
      SED during control, ISC, and reperfusion. Exercise did not alter cellular
      electrophysiology but did influence ectopic rhythms seen with beta-stimulation
      during ISC.

PMID- 7564988
TI  - [Identification of leishmaniasis: current clinical and epidemiological tools].

PMID- 7564987
TI  - [Mauritania: land of men. Health conditions in 1995].

PMID- 7564989
TI  - [Minimal requirements for a laboratory in the tropical zone].

PMID- 7564990
TI  - [Health recommendations for travelers: the latest update].

PMID- 7564991
TI  - [Health cooperation or the unachievable dream].

PMID- 7564992
TI  - [Ebola virus and yellow fever: lessons to learn from the epidemics].

PMID- 7564993
TI  - [Five cases of non-typhoid salmonellosis in patients infected with the human
      immunodeficiency virus in Senegal].
AB  - Among the opportunistic infections observed during infection with human
      immunodeficiency virus, recurrent non-typhoid salmonella bacteriemia has not been
      widely documented in Black Africa. This retrospective study identified 5 cases of
      non-typhoid salmonellosis in a series of 27 seropositive patients, i.e. 18.5%,
      hospitalized over a two-year period in an internal medicine department in
      Senegal. All 27 patients presented general or digestive manifestations and were
      in the stage of full-blown AIDS. The diagnosis was salmonella septicemia in 60%
      of cases. The incidence of salmonella is higher in immunocompromised patients
      than in healthy subjects, particularly in Africa. These infections frequently
      lead to bacteriemia, have a strong tendency to recur, and are highly indicative
      of immunodeficiency. Salmonellosis which is curable should be suspected in
      seropositive African patients presenting general and/or digestive manifestations.

PMID- 7564994
TI  - [Malnutrition and health status of children under five years old in the suburban
      zone of Niamey, Niger].
AB  - In June 1992 prior to a community-based screening campaign for malnourished
      children, a cross-sectional survey was conducted in a semi-urban area located ten
      kilometers from Niamey, the capital city of Niger. Nutritional data gathered from
      a representative sample of children under the age of 5 years were compared to
      corresponding data from the National Center for Health Statistics. Acute
      malnutrition among children under six months was 8%. In the sample as a whole,
      the rates acute and chronic malnutrition were 17.7% (13.4-22.0) and 28.7% (23.4
      33.9) respectively with 4% accuracy. These rates were similar to those of a
      previous regional study made in 1990. Nutritional status was related to the
      identity of the caretaker. Mothers had a mean of 4.07 living children and 0.99
      dead children. The study indicated a child mortality rate of 181 (136-225) per
      thousand. The primary anamnestic causes of death were diarrhea and measles.
      Malnutrition was the fifth cause of death. Twenty-two percent of children
      screened had been sick in the month preceding the study. Low cure rates of the
      malnourished at the nutritional center of Niamey (7.42%) and high level of
      chronic malnutrition underline the need for solutions better suited to semi-urban
      areas.

PMID- 7564996
TI  - [One-year follow-up of 466 nerve decompressions in 123 lepers during multidrug
      therapy in Madagascar].
AB  - Surgical decompression of nerves in patients with leprosy is a simple procedure
      that can be used in developing countries. At the leprosy center of Ambatoabo on
      the east coast of Madagascar, 466 nerve decompressions were performed on 123
      subjects and results were evaluated by the same examiner 15 months later. All
      subjects were undergoing multidrug therapy at the time of the procedure. The
      decision to perform surgery was based on recent onset of sensory and motor
      neurologic signs and on progression or persistence of symptoms despite
      administration of prednisolone. Decompression led to pain relief in 100% of cases
      and regression of sensory disturbances in 97%. Sensory recovery in the plantar
      ulcers of the foot was obtained in 80% of cases and motor performance improved in
      61%. These favorable results confirm the value of surgical decompression to
      prevent sequels of leprosy and the feasibility of this procedure in remote areas.

PMID- 7564995
TI  - [Epidemiologic, clinical and hematologic profile of K Woolwich hemoglobinopathies
      in Ivory Coast].
AB  - From 1968 to 1992, the hematology laboratory at the University Hospital Center of
      Abidjan performed 197705 hemoglobin electrophoreses. Isoelectric focusing using
      the Basset technique allowed identification of hemoglobin K Woolwich. This
      abnormality of hemoglobin structure (beta 132 (H10) Lys ... Glu) was detected in
      130 cases, i.e. 0.065%. It was homozygous in 3 cases, heterozygous in 110 cases,
      and associated with other hematologic abnormalities in 17 cases. The abnormality
      was asymptomatic and did not cause any hematological disturbance. Due to
      autosomal transmission, hemoglobin K Woolwich is a trait of Akan populations (75%
      of cases) in which it is dominant in the Attie subgroup. Given its ethnic
      specificity, this abnormality is of anthropological interest.

PMID- 7564997
TI  - [Disseminated Histoplasma capsulatum histoplasmosis in African AIDS patients (3
      cases)].
AB  - The authors describe three cases of Histoplasma capsulatum histoplasmosis that
      occurred in black AIDS patients living in France but originally from Guinea and
      Ivory Coast. In all three cases histoplasmosis was disseminated with fever. In
      two cases there were cutaneous manifestations. One patient had renal
      insufficiency and nephrotic syndrome and another presented ulcerative colitis
      with histoplasma in the chorion. The outcome was favorable in two patients. These
      three cases are in addition to the five previously reported cases in african AIDS
      patients. These cases stress the need for awareness of this opportunistic
      infection as a complication of AIDS in patients from Black Africa.

PMID- 7564998
TI  - [Chronic myeloid leukemia manifesting as gout. Reflections on secondary gout in
      Black Africa].
AB  - This report describes the case of a 63-year-old obese and alcoholic butcher who
      suffered two episodes of distal oligoarthritis. These episodes were attributed to
      gout on the basis of response to colchicine and demonstration of hyperuricemia.
      Given the presence of hepatomegaly, splenomegaly and hyperleukocytosis, a sternal
      puncture and myelogram were performed and led to diagnosis of chronic myelogenous
      leukemia. In addition to the classic predisposing factors for gout, sickle cell
      anemia could be implicated in Black Africa. Longer life expectancy for patients
      with sickle cell anemia could increase the incidence of gout in Black Africa.

PMID- 7564999
TI  - [Choanal atresia: an abnormality not to be overlooked. Study of three cases in
      the University Hospital Center of Lome, Togo].
AB  - Choanal atresia is an uncommon congenital malformation which the midwife or
      obstetrician must recognize at birth. In this report the authors describe three
      cases observed at the University Hospital Center of Lome, Togo, in which
      diagnosis was made late, i.e. at the ages of 7 days, 13 days and 8 months.
      Atresia identified by rhinoscopy was bilateral in one case and unilateral in two
      cases. All three cases were treated by transnasal divulsion, using a rubber
      catheter in 2 cases and a curette in one case, followed by calibration with a
      Portex catheter that was removed after two months. At 6 months after treatment,
      all three children presented normal nasal ventilation. Since it can be easily
      diagnosed and treated, choanal atresia is curable and better training is needed
      to ensure detection at birth.

PMID- 7565000
TI  - [Role of hysterosalpingography in the evaluation of infertility in Black Africa].
AB  - Infertility affects a great number of women in Black Africa and tubal obstruction
      seems to be common. Because of this high incidence, an accurate test for tubal
      patency is needed and several examinations have been proposed. Recent reports
      indicate that the method of choice is hysterosalpingography since it is simple,
      quick, and reliable. Concordance with laparoscopy, the gold standard, is 85% for
      assessment of tubal patency and 75% for detection of tubal abnormalities. Due to
      the lack of radiological facilities in most hospitals in Black Africa, a
      simplified examination is proposed and seems to be useful as an initial screening
      test. This simplified test consists of obtaining a delayed anteroposterior image
      after a brief walk. The most severe complication of hysterosalpingography is
      pelvic infection which occurs in 2 to 4% of cases and requires prophylactic
      antibiotic therapy. Interestingly an increase in pregnancy rate has been observed
      in the months after hysterosalpingography. Recent reports concerning infertility
      workups in developing countries confirm that the method of choice for assessment
      of tubal function is hysterosalpingography provided that the risk of infection
      can be controlled.

PMID- 7565001
TI  - [Pseudo-parasites in histology and cytopathology].
AB  - When interpreting smears and specimens, histologist and cytopathologists can be
      misled by images mimicking micro-organisms especially parasites such as protozoa,
      mycotic agents or helminths. Although some of these pitfalls are well-known,
      others can be problematic especially if nature of the contaminant is the same as
      that of the parasite that it mimics. False protozoa parasites can correspond
      either to exogenous agents such as spores, remnants of human cells, or inert
      exogenous particles. Pseudo-yeast images can be due to pollen, starch or soot but
      especially to cells such as macrophages, spermatozoids, and neurons or to various
      inert bodies such as pigments or calcifications. Pseudomycotic filaments can
      result from vegetable silk, asbestos bodies, radiate granules or fibrin.
      Curschmann's spirals and vegetable fibers can be confused with helminths and
      bacterial particles or pollen with helminth eggs.

PMID- 7565002
TI  - [Burundi: humanitarian mission (January-April 1994)].
AB  - The 1993 assassination of the President of the Republic of Burundi led to a
      bloodbath resulting in the killing of 700 000 people and 300 000 refugees in
      camps scattered throughout the country. After the emergency surgery phase, the
      French cooperation which was in charge of health care in the Gitega sector
      requested a humanitary mission. Two public health physicians, a polyvalent
      clinical physician, and two field nurses were sent. All were armed service
      personnel. From January to April 1994, after a preliminary assessment of the
      situation, this mission took charge of health services as well as administrative
      services for the population of the region including some 10 000 refugees.
      Epidemiologic surveillance was carefully organized. During the first quarter of
      the year, there were 2451 declared cases of bacterial dysentery, 6738 cases of
      malaria-like fever including 25% confirmed by paristological findings on a study
      of 60 consultants, 87 cases of measles, and 1306 cases of conjunctivitis. There
      were no cases of cholerea or meningoccoal meningitis. A food support program was
      started when it was noted that the overall rate of acute malnutrition among
      refugee children under the age of 5 years was 25% (weight/height ratio less than
      minus 2 standard deviations or observation of edema). At the present time the
      situation in the sector is back to normal and the health care system is operating
      satisfactorally. However the situation in neighboring Rwanda could have adverse
      effects on the political stability of Burundi.

PMID- 7565003
TI  - [Senegal: installation of a microcomputer in the emergency admission service of
      the Ziguinchor Regional Hospital].
AB  - An Emergency Department was opened at the Regional Hospital of Ziguinchor in
      August 1993. Although adapted to local conditions, facilities are state-of-the
      art and allow 24-hour reception of patients regardless of the gravity of their
      condition. There are many people involved: family, police, firemen,
      administration ... and there are also many questions. Records must be efficiently
      and accurately managed and the computer is the ideal tool for this purpose. The
      department was able to install a system at a particularly low cost since the PC
      computer and Epi-Info software were provided at no charge by the World Health
      Organization. To ensure consistent data entry, a coding system was used with some
      codes being specific to the department. Thanks to this system the department now
      has a 24 hour source of information for day-to-day management, statistical
      reporting, regional morbidity assessment, comparison of performance with similar
      facilities, and patient follow-up. Our experience shows that this type of low
      cost computer system and simple processing techniques are perfectly suited to the
      special requirements of medical practice in Black Africa.

PMID- 7565004
TI  - [Recurrent lepromatous leprosy in conventional triple therapy: value of the
      rifampicin-ofloxacin combination].

PMID- 7565005
TI  - [Prolonged QT interval and cardiac toxicity due to halofantrine].

PMID- 7565006
TI  - [Hepatic amebiasis and hemorrhagic rectocolitis: an accidental association?].

PMID- 7565007
TI  - [Von Recklinghausen neurofibromatosis in Lome, Togo].

PMID- 7565008
TI  - [Fatal hepatitis due to allopurinol in Dakar].

PMID- 7565009
TI  - [Hartmann procedure, indications and results in Yaounde].

PMID- 7565010
TI  - Analysis of the interaction of group A streptococci with fibrinogen,
      streptokinase and plasminogen.
AB  - Group A streptococci demonstrate a number of distinct ways to interact with the
      human fibrinolytic system to acquire unregulatable cell-surface enzymatic
      activity. Interactions between bacteria, fibrinogen, streptokinase and
      plasminogen resulted in acquisition of cell-associated enzymatic activity that
      can lyse fibrin clots despite the presence of the major physiological plasmin
      inhibitor, alpha 2-antiplasmin. Western blot analysis of extracted streptococcal
      surface proteins suggested that binding of fibrinogen to M or M-related proteins
      mediated the capture of streptokinase-plasminogen complexes to the bacteria. The
      enzymatic complex formed by reaction of bacteria with fibrinogen, streptokinase
      and plasminogen was found to be more stable in human plasma than pre-formed
      plasmin bound directly to the same bacteria strain.

PMID- 7565011
TI  - Distribution of the cytolethal distending toxin A gene (cdtA) among species of
      Shigella and Vibrio, and cloning and sequencing of the cdt gene from Shigella
      dysenteriae.
AB  - We investigated the distribution of the cytolethal distending toxin A gene (cdtA)
      among S. dysenteriae, Vibrio cholerae 01 and Vibrio parahaemolyticus by
      polymerase chain reaction (PCR) using primers constructed from the nucleotide
      sequences of Escherichia coli cdtA gene reported independently by Scott and Kaper
      (Infect Immun 1994; 62: 244-51) and by Pickett et al. (Infect Immun 1994; 62:
      1046-51). The cdtA gene reported by Scott and Kaper was found to occur among
      eight of the 35 strains of S. dysenteriae but was not found among V. cholerae O1
      and V. parahaemolyticus. The cdtA gene reported by Pickett et al. was not found
      among S. dysenteriae, V. cholerae O1 and V. parahaemolyticus. To further
      investigate the distribution of the cdtA gene among a large number of Shigella
      spp. (S. dysenteriae, S. flexneri, S. boydii and S. sonnei), and among Vibrio
      spp. (Vibrio cholerae O1, V. cholerae O139 and V. parahaemolyticus) by colony
      hybridization test, we constructed a cdtA gene specific DNA probe by amplifying
      the cdtA gene by PCR with primers designed from the nucleotide sequence of the
      cdtA gene reported by Scott and Kaper. The cdtA gene reported by Scott and Kaper
      was found to occur among eight of the 35 strains of S. dysenteriae and one of the
      100 strains of S. sonnei, but was not found among other species of Shigella or
      among the Vibrio species examined. From one cdtA gene-positive S. dysenteriae
      strain that showed cytolethal distending toxin (CDT) activity on Chinese hamster
      ovary cells, we cloned and sequenced the entire cdt gene comprising cdtA, cdtB
      and cdtC genes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565012
TI  - Identification of binding proteins for pertussis toxin on pancreatic beta cell
      derived insulin-secreting cells.
AB  - The ability of pertussis toxin (PT) to recognize and bind to surface proteins on
      cells derived from pancreatic insulin-secreting beta cells and alpha cell-like
      glucagon-producing cells was investigated employing HIT-T15 (beta cell-derived)
      and In-R1-G9 (alpha cell-like) cell lines. PT recognition of membrane binding
      proteins on HIT-T15 and In-R1-G9 cells was first assessed with immunofluorescence
      microscopy in tissue culture. Both cell lines were equally well recognized by PT.
      N-octylglucoside extracts of whole cells and isolated membranes were separated by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and blotted
      onto nitrocellulose membranes. PT, the B-oligomer, or the isolated PT dimers S2
      S4 and S3-S4 recognized distinct proteins in HIT-T15 and In-R1-G9 cells of about
      220 kDa. Recognition by the sialic acid specific Sambucus nigrica lectin
      identified these proteins as sialoglycoproteins. Incubation of the blotted
      membrane proteins with sialidase or pretreatment of PT with anti-PT polyclonal
      antibodies abolished the recognition and binding of these proteins by PT. To
      demonstrate that these glycoproteins are also able to transduce PT mediated
      effects and thus might serve as PT binding proteins, the stimulation of insulin
      secretion in HIT-T15 cells was assessed. As the secretion of insulin in HIT-T15
      cells increased about 30% upon interaction with PT it was concluded that these
      glycoproteins are indeed functional as PT receptors.

PMID- 7565013
TI  - A serum-sensitive, sialyltransferase-deficient mutant of Neisseria gonorrhoeae
      defective in conversion to serum resistance by CMP-NANA or blood cell extracts.
AB  - A stable, sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62
      totally defective in CMP-NANA-dependent lipopolysaccharide (LPS) sialylation was
      isolated by insertion mutagenesis with transposon Tn 1545-delta 3 and screened
      for unlabelled colonies following incubation with CMP-14C-NANA. In contrast to
      the parental strain which became serum resistant on incubation with CMP-NANA or
      blood cell extracts, the mutant, JB1, remained serum sensitive. French press
      extracts of strain F62 catalysed LPS sialylation, but corresponding extracts of
      the mutant were inactive. Five LPS components were detected by SDS-PAGE in the
      parental strain. Five components of the same Mr were also found in the mutant.
      Three identical components were detected by Western blotting using MAb 3F11,
      which recognizes the Gal beta 1-4GlcNAc groups in the conserved LPS components of
      F62 which can be sialylated. The mutant, JB1, is therefore deficient in the
      sialyltransferase that is essential for both LPS sialylation and conversion of
      serum-sensitive gonococci to serum resistance by either CMP-NANA or blood cell
      extracts. No evidence was obtained for an LPS sialylation pathway by blood cell
      extracts that is independent of CMP-NANA.

PMID- 7565015
TI  - Mouse hepatitis virus A59-induced demyelination can occur in the absence of CD8+
      T cells.
AB  - Mouse hepatitis virus causes a chronic demyelinating disease in C57BL/6 mice.
      While early studies suggested demyelination is due to direct cytolytic effects of
      virus on oligodendrocytes, there is increasing evidence for the involvement of
      the immune system in the mechanism of demyelination. In this study we have asked
      whether demyelination can occur in the absence of functional MHC class I
      expression and CD8+ T cells. We infected transgenic mice lacking expression of
      beta 2 microglobulin (beta 2 M -/- mice) with MHV-A59. In beta 2M-/- mice, virus
      was much more lethal than in either of the parental strains used to produce the
      mice; furthermore, while clearance from the CNS did occur in beta 2M-/- mice, it
      was slower than in C57BL/6 mice. This is consistent with the importance of CD8+
      cells in viral clearance. Because of the increased sensitivity of the beta 2M-/-
      mice to infection, only low levels of virus could be used to evaluate chronic
      disease. Even at these low levels, demyelination did occur in some animals. To
      compare infection in beta 2M-/- and C57BL/6 mice we used a higher dose of an
      attenuated variant of MHV-A59, C12. The attenuated variant induced less
      demyelination in C57BL/6 mice compared to wild type A59, but the levels observed
      were not significantly different from those seen in beta 2M-/- mice. Thus, MHV
      induced demyelination can occur in some animals in the absence of MHC class I and
      CD8+ cells.

PMID- 7565014
TI  - Molecular investigation of the role of ApxI and ApxII in the virulence of
      Actinobacillus pleuropneumoniae serotype 5.
AB  - The extracellular hemolytic toxins (ApxI and ApxII) of Actinobacillus
      pleuropneumoniae are thought to be important factors in this microorganism's
      virulence and the pathogenesis of swine pleuropneumonia. Using the polymerase
      chain reaction, the apxI locus of a non-hemolytic, avirulent mutant of A.
      pleuropneumoniae serotype 5 (mIT4-H) generated by chemical mutagenesis (Inzana T.
      J., Todd J., Veit H. P. Microb Pathog 1991; 10: 281-96) was found to contain
      deletions that affected major parts of the entire apxICABD operon, thus
      inactivating each gene in the operon. The apxII locus was not affected.
      Monoclonal antibodies to ApxI and ApxII were used to confirm that ApxI was not
      synthesized, and that ApxII was synthesized but not secreted from the cell. The
      apxICABD genes and apxIBD genes were cloned into a broad host range vector to
      obtain plasmids pJFF800 and pJFF801, respectively. Each recombinant plasmid was
      electroporated into strain mIT4-H to obtain strain mIT4-H/pJFF800 and strain mIT4
      H/pJFF801, respectively. Strain mIT4-H/pJFF800 exported ApxI and ApxII, and
      produced hemolytic activity comparable to or exceeding that of wild type strain
      J45. Strain mIT4-H/pJFF801 exported only ApxII and produced weak hemolytic
      activity. Strain mIT4-H/pJFF800 was virulent in mice, and had an LD50 of about 2
      x 10(6) colony forming units. In contrast, mIT4-H/pJFF801 and mIT4-H were
      essentially avirulent in mice, and LD50s for these strains could not be
      calculated. Strain mIT4-H/pJFF800 was virulent in pigs and caused lethal
      pleuropneumonia, whereas parent strain mIT4-H was avirulent. Strain mIT4
      H/pJFF801 was also able to induce pleuropneumonia in pigs, although a higher dose
      was required to induce lesions similar to those caused by mIT4-H/pJFF800. Thus,
      A. pleuropneumoniae strains that produce ApxI and ApxII require ApxI for full
      virulence and toxic activity in pigs. However, other factors including ApxII
      contribute to the virulence of A. pleuropneumoniae in pigs.

PMID- 7565016
TI  - Catabolite repression of the adhesion of Vero cytotoxin-producing Escherichia
      coli of serogroups O157 and O111.
AB  - The virulence traits that mediate Vero cytotoxin-producing E. coli (VTEC)
      adherence are unclear. Many VTEC strains possess the eaeA gene which is involved
      in the attaching and effacing effects of enteropathogenic E. coli (EPEC). Most
      eae-positive VTEC adhered to HEp-2 cells in a localized manner; however some
      strains did not adhere. Thus we investigated the adhesion of poorly adherent
      strains, especially those of serogroups O111 and O157. To establish a model, the
      adherence to HEp-2, INT407 and Caco-2 cells of 12 O157 VTEC and six O111 VTEC
      isolated from cases of human infection were studied after growth of the bacteria
      under different conditions. For adhesion tests mannose is usually added during
      prior broth culture of the bacteria, and during the period of attachment, so that
      any adhesion due to mannose-sensitive type 1 pili is inhibited. Bacteria cultured
      in peptone water in the absence of mannose adhered to all three lines; there were
      localized clusters of bacteria on 1%-82% cells, whether mannose was present
      during the attachment period or not. Bacteria grown in the presence of D-mannose,
      or any other sugar that was metabolized, showed little adherence (range 0-9%).
      alpha-Methyl-glucoside also caused marked inhibition of adhesion. It was
      concluded that inhibition of adhesion was due to catabolite repression.

PMID- 7565017
TI  - Distribution of genes encoding cholera toxin, zonula occludens toxin, accessory
      cholera toxin, and El Tor hemolysin in Vibrio cholerae of diverse origins.
AB  - A large collection of 1154 strains of Vibrio cholerae of diverse origins
      including serogroups 01 and 0139 and those belonging to the non-01 and non-0139
      (non-01:non-0139) serogroups were examined with a battery of DNA probes specific
      for cholera toxin (CT), zonula occludens toxin (ZOT), accessory cholera toxin
      (ACE) and El Tor hemolysin (HLY) to determine the distribution of genes among
      wild strains and to understand the importance of these factors in the
      pathogenesis of the disease cholera. Among the 01 clinical isolates, the majority
      of the strains had an intact core region (ctx, zot, ace) and also possessed the
      hlyA gene. Although rare, strains of 01 with natural deletions of the ctx, zot
      and/or ace genes were also detected. The absence of the virulence genes
      comprising the core region and the presence of the hlyA gene dominated the 01
      environment, food isolates and the clinical and environmental non-01: non-0139
      strains of V. cholerae. All the 0139 strains examined in this study possessed
      genes located in the core region and the hlyA gene. Among all the virulence
      associated genes examined, the hlyA gene was the most conserved genetic element
      in V. cholerae independent of biotypes and serogroups.

PMID- 7565018
TI  - Testicular autotransplantation for the intra-abdominal testis.
AB  - Oftentimes patients with intra-abdominal testes require more than the standard
      procedure to accomplish orchiopexy. Division of the spermatic vessels has been
      one mainstay of operative approaches for the intra-abdominal testis since Fowler
      and Stephens (Congenital Malformations of Rectum, Anus, and Genitouriary Tracts,
      chapter 19, pp 306-320, 1963) provided an anatomically rational basis for this
      procedure. Silber and Kelly (J Urol, 115:452-454, 1976) first described using a
      microvascular anastomosis to bring extra blood supply to the testicle after
      mobilization of a high intra-abdominal testicle into the scrotum; however, this
      approach has not been adopted by many for a number of reasons. The microvascular
      skill and instrumentation required for a successful anastomosis are not
      universally available and there is a misconception that the procedure is a
      lengthy one (Bianchi, Br J Urol 56:521-524, 1984; Bogaert et al., Urology 42:182
      188, 1993). We present our series for testicular autotransplantation used over a
      17 year period with a greater than 95% success.

PMID- 7565019
TI  - Penile microvascular arterial bypass surgery.

PMID- 7565020
TI  - Staged approach to phallic construction and penile reconstruction.

PMID- 7565021
TI  - Ulnar forearm phallic construction and penile reconstruction.

PMID- 7565022
TI  - Prosthetic implantation after phallic construction.

PMID- 7565024
TI  - Epididymovasostomy.
AB  - There are a variety of causes of epididymal obstruction, but the most frequent
      indication for epididymovasostomy today is obstruction following vasectomy. We
      have seen significant advances over the last few decades in our techniques for
      reconstructing the proximal excurrent ductal system in order to restore sperm to
      the ejaculate and fertility in men with azoospermia secondary to epididymal
      obstruction. The patency rates for epididymovasostomy have improved significantly
      with the use of microsurgical techniques and specific tubule anastomosis. The
      level of anastomosis plays a crucial role in eventual fertility. These
      microsurgical techniques are tedious and difficult to master but practice and
      meticulous attention to detail are rewarded by excellent results.

PMID- 7565023
TI  - Microscopic vasovasostomy: current practice and future trends.

PMID- 7565025
TI  - Microsurgical sperm aspiration coupled with the advanced reproductive
      technologies.

PMID- 7565026
TI  - Gamete microsurgery for assisted fertilization.
AB  - Several methods of gamete microsurgery have been proposed to facilitate the union
      of the spermatozoon and oocyte in infertile couples. Partial zona dissection,
      subzonal sperm insertion, and intracytoplasmic sperm insertion are the three
      techniques currently being used for assisted fertilization in human in vitro
      fertilization laboratories. Fertilization and pregnancy rates after partial zona
      dissection and subzonal insertion have been variable and rather low. Recent
      reports of relatively high fertilization and pregnancy rates achieved after
      intracytoplasmic sperm insertion have rejuvenated interest in gamete
      microsurgery. Methods for each procedure are described. Studies which have
      attempted patient selection for gamete microsurgery are discussed.

PMID- 7565027
TI  - Can varying flow velocity across an arterial anastomosis prevent thromboembolic
      injury?
AB  - In this study, simulated "poor" repairs applied to transverse incisions in the
      iliac arteries of 40 rats were the basis for comparing the effect of variations
      in blood flow on thromboembolism. Using vital microscopy and digital image
      processing, we performed 2 experiments. In the first experiment (n = 20), the
      reduction of post-repair blood flow by approximately 50% resulted in an 83%
      reduction in the total number of emboli appearing in the microcirculation of the
      cremaster muscle distal to the repair. In the second experiment (n = 20), the
      same reduction in blood flow typically resulted in larger repair-site thrombi
      which required significantly more time to grow to their maximum size. We conclude
      that reducing pedicle artery blood flow to approximately half in our rat model
      during reperfusion can protect the downstream microcirculation from embolic
      injury without increasing the incidence of thrombotic occlusion.

PMID- 7565029
TI  - [Diagnosis and treatment of myasthenia gravis. Experience 1974-1992].
AB  - Between 1974 and 1992, 118 patients with Myasthenia gravis (MG) were studied in
      our Hospital; 92 patients, followed up for longer than 6 months, were surveyed
      for therapeutical results. Patients were categorized according to Osserman
      criteria; 22 belonged to group I; 77 to group II; 4 to group III and 15 to group
      IV. MG predominated in females, the ratio was 1.87:1.0. This predominance was
      more obvious in patients below 35 years of age (2.68:1.0) than above (1.18:1.0).
      The greatest prevalence was found at the 3rd decade of life. The assessment of
      the diagnostic test is as follows: 1) edrophonium test was positive in 97% of 93
      patients; 2) supramaximal repetitive stimulation performed in 3 different nerves
      yielded positive results in 83% of 118 patients. It is worth noting that the test
      was positive in 92% of patients with generalized MG while only 48% of those with
      ocular MG displayed positive results; 3) sera antiacetycholine receptor
      antibodies (ACRA) quantification produced positive results in 88% of the patients
      with generalized MG and in 33% of ocular MG. Altogether the positivity of this
      test was 83%; 4) passive transfer of patients sera (25 generalized and 2 ocular
      MG forms) to mice and measurement of mepp's amplitude in the phrenic-diaphragm in
      vitro preparation yielded positive results in 100% of the tested cases. Once the
      diagnosis was achieved, the characteristics of the thymus were studied combining
      pneumomediastinography and linear tomography (PT) in 60 patients. Thorax Computed
      tomography (CT) was performed in 51 patients. Of those patients who underwent
      thymectomy, the coherence between radiological and histological diagnosis for PT
      was 100% while for CT just 60%. More recently 14 patients were studied by
      combining both procedures. Reliability of this technique is currently under
      study. Therapeutical assessment was carried out adscribing patients to 5
      different groups according to their response after treatment withdrawal; group 2:
      Improved, neither symptoms nor signs; group 1: Remission, neither symptoms nor
      signs while on medication or minimal disability without medication; group 3:
      Unchanged while on medication; group 4: Worse, patients with more severe or
      frequent signs and symptoms despite being on treatment, group 5: Death, patients
      who died due to respiratory failure. Groups 1 and 2 were considered successful
      while 3, 4 and 5 as unsuccessful. Treatment was based on the administration of
      anticholinesterase drugs (piridostigmine, neostigmine) in 113 patients. Of these,
      35 received those drugs as the only medication of whom 39% obtained successful
      results. Steroids (methylprednisone) were administered to 75 patients, in 40
      cases combined with anticholinesterase drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7565028
TI  - Effect of isovolemic hemodilution with dextran and albumin on thrombus formation
      in artificial vessel grafts inserted into the abdominal aorta of the rabbit.
AB  - The effects of isovolemic hemodilution with dextran-70 and albumin on thrombus
      formation in artificial arterial grafts were investigated. A
      polytetrafluoroethylene graft (PTFE, length 13 mm, inner diameter 3 mm) was
      inserted into the abdominal aorta of rabbits. Three groups of animals were
      studied; 1) animals receiving isovolemic hemodilution with dextran-70 (10 ml/kg
      body weight), 2) animals receiving isovolemic hemodilution with albumin (10 ml/kg
      body weight), and 3) nonhemodiluted controls. The blood flow increased by about
      70% and 60% after the hemodilution with dextran and albumin, respectively, and
      remained high in the hemodiluted animals, after insertion of the graft. After 2
      days, the vessel graft was removed and weighed. The thrombus mass was separately
      weighed. The results suggest that isovolemic hemodilution with both albumin and
      dextran is associated with a marked increase in blood flow in the rabbit.
      Hemodilution with dextran also reduced the amount of thrombus formation on the
      inner wall of the graft.

PMID- 7565030
TI  - [Evaluation of the alarm reaction induced by blood pressure determination].
AB  - The purpose of this paper was to evaluate the characteristics of the alarm
      reaction that induces an increase of blood pressure (BP) above the "basal" when
      it is measured in the clinic. This "supplemental" increase that is added to the
      "basal" pressure was analyzed through the decrease of systolic blood pressure
      (SBP) along ten consecutive measurements separated by 3 minutes intervals in 85
      patients with BP values within a wide range (Table I). 91% of the patients showed
      a decrease in consecutive measurements and only 9% showed increases or no
      significant change in SBP values. The decrease showed good correlation with the
      exponential decay (r = 0.99). The asymptote was for the SBP of -8.7 +/- .81 mmHg
      (P < 0.01) (Fig. 2) with a time constant T (tau) of 4.7 +/- 1.3 minutes. There
      was no correlation between the magnitude of the decrease and the BP levels, which
      does not support the idea that this reaction would be increased in hypertensives.
      The decrease of DBP was lower (3.87 +/- .71 mmHg (P < 0.01) but with similar
      characteristics (Fig. 3). If we consider the characteristics of the exponential
      decay and the fact that after 4 or 5 measurements we arrive at values near the
      asymptote, basal BP could be simply determined by the average of 2 or 3
      determinations with 3 minutes intervals measured after discarding the first two
      or three readings obtained in the same conditions or by calculating the
      exponential decay from the equation SBP = Po.e-1/T + As (Fig. 6).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7565031
TI  - [The role of food in cholera transmission].
AB  - The spreading of cholera, from Peru to other Latinoamerican countries in 1991,
      raised questions regarding food safety, food transportation and handling.
      Control, prevention and risks implied in food import-export were also matters of
      concern. We deemed it interesting to determine the viability of Vibrio cholerae
      in wide consumption food locally. Selected food had different intrinsic
      characteristics such as: acidity (pH), water activity (aw), chemical composition,
      indigenous flora and other biologic and physic parameters. Twenty food products
      were contaminated with V. cholerae O1, Ogawa, toxigenic and not toxigenic
      strains: yoghurt, cream cheese, apricot marmelade, hip rose marmelade,
      mayonnaise, italian pasta for "empanadas", "dulce de leche", meat sausage, meat
      and spinach ravioli, margarine, milk dessert (made with cocoa, milk confiture,
      starch and additives), lettuce, tuna fish, ricotta and sterilized milk. Table I
      shows the viability of V. cholerae in tested foods, its pH and the reasons why
      the experiments were ended: 75% of the products studied could tolerate the
      development of the microorganism for a period ranging from one day (pasta for
      "empanadas") to ninety days (sterilized milk). Foods with acredity higher than pH
      5.5 did not favor the growth of Vibrio. When pH was neutral or slightly acid,
      viability persisted independently from aw, microbial antagonisms and other
      physic, chemical or biologic parameters. Nevertheless, other factors such as:
      surface adherence, amino acids, magnesium and environmental influences not yet
      well determined, could eventually modify the persistence of V. cholerae in food.
      According to this study, most food products could tolerate growth and persistence
      of the infectant agent, up for three months in some cases.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7565032
TI  - [Raul J. Usandivaras].

PMID- 7565033
TI  - [Use-dependence of propafenone. Clinical demonstration of the hypothesis of
      modulated receptors].
AB  - The aim of this study was to assess use-dependence in patients with ventricular
      premature contractions (VPC's) treated with propafenone, by means of the increase
      in heart rate using transesophageal atrial pacing. It was also analyzed whether
      this phenomenon was related to the antiarrhythmic effect. Fifteen patients with
      more than 30 symptomatic VPC's/sour were evaluated. Esophageal pacing was
      performed with cycles of 600 and 400 msec during periods of 1 min and with
      simultaneous recording of 2 or 3 EKG leads with a paper speed of 100 mm/sec.
      Holter monitoring (HM) was carried out in all patients. Propafenone was
      administered in doses of 450 and 900 mg/day, during 5-7 days, at which moment
      another HM and esophageal stimulation were repeated. The QRS duration (pre
      treatment) was 82.6 +/- 13.5 msec (basal) and 82.4 +/- 13 msec during pacing with
      600 msec cycle length (p: NS). The QRS duration with P (900 mg/day) was 96.6 +/-
      20 msec (basal) (p:NS vs. pre-treatment) but during atrial pacing with 600 msec
      cycle length it increased to 109.3 +/- 23 msec (p < 0.0004). This use-dependence
      was also observed with pacing at 600 msec in patients receiving doses of 450
      mg/day: 95.3 +/- 13 msec (p < 0.0001 vs. baseline QRS) (Table 1). IN CONCLUSION:
      1) there was no significant increase in the QRS duration with P without pacing;
      2) propafenone showed use-dependence during atrial stimulation, even with cycle
      length of 600 msec and with the lower doses.

PMID- 7565034
TI  - Ritanserin pharmacokinetics in abstinent chronic alcoholics.
AB  - Ritanserin is a thymosthenic agent with an extensive hepatic metabolism and long
      elimination half life in healthy volunteers. It has been used in abstinent
      chronic alcoholic patients showing an interesting performance in this condition.
      Ritanserin pharmacokinetics has only been evaluated in single dose healthy
      volunteer studies and, on the other hand, chronic use of the drug in alcoholic
      patients during withdrawal period could be anticipated. Therefore, the objective
      of the present study, is to assess the cumulating kinetics of the serotonin
      antagonist during chronic administration. Ten abstinent alcoholic patients were
      included in an open study. The drug was administered at a daily dose of 10 mg for
      28 days and the active phase was preceded by a seven-day wash out period with
      placebo. Blood samples were taken on the 1st, and 28th, day of treatment, 24
      hours after taking the drug. Urine samples were taken during the night before the
      second and 28th dose. Plasma and urine ritanserin concentration was measured by
      high performance liquid chromatography. Very large variations in initial and
      steady state concentrations (CV = 65 and 52% respectively) were found, which is
      reflected in the large variability of the calculated pharmacokinetic parameters.
      Ritanserin cumulation factor (R) was 6.9 +/- 8.3 (mean+SEM). Two patients showing
      extensive accumulation had prolonged elimination half lives (433 and 279 hours)
      that are explained mostly by an expansion of the volume of distribution and, to a
      lesser extent, by diminished clearance.

PMID- 7565035
TI  - A maternally-inherited alteration in the T cell repertoire of BALB/c mice.
AB  - A number of milk-borne exogenous mammary tumor viruses (MMTV) infect mice shortly
      after birth and, when expressed, produce superantigens. The expression of these
      superantigens mediate the progressive deletion of T cells expressing specific V
      beta products. Here we describe a maternally-inherited alteration in the T cell
      repertoire in one colony of BALB/c mice which has not been reported up to now.
      This alteration involves the deletion of V beta 2+ and 14+ CD4+ T cells and
      correlates with a high incidence of mammary tumors, suggesting the involvement of
      a superantigen(s) probably transmitted through an exogenous MMTV in milk.

PMID- 7565036
TI  - [Malignant peritoneal mesothelioma. An infrequent cause of prolonged fever
      syndrome and leucocytosis in a young adult].
AB  - Peritoneal mesothelioma is a rare neoplasia usually associated with exposure to
      asbestos. The incidence in the population not in contact with asbestos is of one
      per million per year. The disease is most common in males over the age of 40,
      with signs and symptoms of neoplasic disease together with abdominal pain and
      ascitis with or without a palpable abdominal mass. We report the case of a young
      male without a history of exposure to asbestos who presented with prolonged
      fever, leukocytosis and a septated peritoneal exudate. With a presumptive
      diagnosis of peritoneal tuberculosis, the patient received empirical
      antituberculosis treatment. Because the clinical picture persisted and
      microbiological studies remained negative, a second exploratory laparotomy was
      performed which demonstrated the presence of a malignant epithelial peritoneal
      mesothelioma.

PMID- 7565037
TI  - [Treatment of motor fluctuations in Parkinson's disease with subcutaneous
      injections of apomorphine].
AB  - Sixteen patients with Parkinson's disease and severe motor fluctuations were
      treated with subcutaneous injections of apomorphine and followed up prospectively
      for a year. The use of the drug improved the number of daily "off" hours by 52%,
      while treatment efficacy remained constant for a year without the appearance of
      tolerance (ANOVA with repeated measurements:p = 0.0002). No severe adverse effect
      or any justifying treatment discontinuance were recorded. Apomorphine proved a
      safe and reliable drug for the treatment of motor fluctuations.

PMID- 7565038
TI  - [Bronchial obstruction due to carcinoma with psammoma and metastasis].

PMID- 7565039
TI  - [Dolichoectatic intracranial arteries. Advances in images and therapeutics].
AB  - Dolichoectasia of intracranial arteries is an infrequent disease with an
      incidence less than 0.05% in general population. It represents 7% of all
      intracranial aneurysms. Commonly seen in middle age patients with severe
      atherosclerosis and hypertension, the affected arteries include the basilar
      artery, supraclinoid segment of the internal carotid artery, middle, anterior and
      posterior cerebral arteries; males are more frequently affected. The clinical
      features of these fusiform aneurysms are divided in three categories: ische-mic,
      cranial nerve compression and signs from mass effect. Hemorrhage may also occur.
      Nine patients with symptomatic cerebral blood vessel dolichoectasias are
      presented. Six of them were males with moderate or severe hypertension. Lesions
      were confined to the basilar artery in 3 cases, carotid arteries and the middle
      cerebral artery in 1 case, and both systems were affected in 4 patients. Middle
      cerebral arteries were affected in 5 cases and the anterior cerebral artery in
      one. An isolated fusiform aneurysm of the posterior cerebral artery is also
      presented (case 8) (Table 3). Motor or sensory deficits, ataxia, dementia,
      hemifacial spasm and parkinsonism were observed. One patient died from cerebro
      meningeal hemorrhage (Table 2). All patients were studied with computerized axial
      tomography of the brain, 5 cases with four vessel cerebral angiography, 4 cases
      with magnetic resonance imaging (MRI) and case 5 with MRI angiography. Clinical
      symptoms depend on the affected vascular territory, size of the aneurysm and
      compression of adjacent structures. The histopathologic findings are atheromatous
      lesions, disruption of the internal elastic membrane and fibrosis of the muscular
      wall. The resultant is a diffuse deficiency of the muscular wall and the internal
      elastic membrane. Recent advances in neuroimaging such as better resolution of CT
      scan, magnetic resonance images (MRI) and MRI angiography increased the diagnosis
      of this pathology showing clearly the affected vessels. This avoids the use of
      conventional or digital subtraction angiography, reserved only for diagnosing
      suspected saccular aneurysm, evidence of subarachnoid hemorrhage or planning
      surgical treatment. The treatment of this entity may be medical or surgical.
      There is evidence suggesting a more favorable outcome with anticoagulation
      therapy, although antiaggregation is a reasonable alternative. In our experience
      no difference in clinical outcome was evident. Surgical treatment of this type of
      aneurysm includes intra- or extracranial occlusion of parent artery, clipping or
      aneurysm trapping, tourniquet occlusion, and circumferential wrapping with clip
      reinforcement. Endovascular occlusion has been accomplished with detachable
      balloon technique or coils. No surgical attempt was done in our cases. The
      prognosis is variable depending on the patients age, vessels involved and
      clinical complications.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7565040
TI  - [Metabolic evaluation at the time of the first renal lithiasis episode].
AB  - There are little doubts about the need of studying thoroughly every patient with
      recurrent renal lithiasis. However, the behavior to be followed after the first
      renal calculi remains controversial. For that reason, we decided to answer a
      series of questions after which, we formulate our own criteria: Which is the
      recurrence rate after the first calculi? Has a patient with recurrent lithiasis,
      the same metabolic disarrangement as a patient who has his first episode? Is the
      family history of both kidney stone patients the same? Which is the morbility of
      both groups? We answered these questions with data drawn from 200 of our patients
      (100 with first episode and 100 with recurrent lithiasis) and a review of the
      medical literature. The patients with their first episode of lithiasis correspond
      to the same population of patients with recurrent episodes, but they are detected
      at different moments of their stone disease. This was concluded since both groups
      of patients had the same metabolic disarrangement with predominance of
      hypercalciuria and alteration in uric acid metabolism. Furthermore, the family
      history was practically the same in both groups (39% in first episode, 41% in
      recurrent lithiasis) and so was the morbility. Therefore, we propose the
      following conduct: 1. every patient with renal lithiasis should be studied
      starting at the first episode, from the urological and metabolic point of view;
      2. the initial metabolic studies have to be as extensive as possible in order to
      aim for specific treatment from the start in order to prevent a recurrence, and
      in the case of hypercalciuric patients to prevent secondary osteopenia.

PMID- 7565041
TI  - [Nobel Prize in medicine 1994: Martin Rodbell and Alfred Gilman. Signal
      transduction].

PMID- 7565042
TI  - [Converting enzyme inhibitors in acute myocardial infarct and heart failure].

PMID- 7565044
TI  - [Trends in the pharmacotherapy of chronic airflow obstruction in Argentina: 1983
      1990].

PMID- 7565043
TI  - [Mutant mice in experimental oncoimmunology].

PMID- 7565046
TI  - [Bacterial sacroileitis. Clinical findinds and clinical course in 9 cases].
AB  - Since septic sacroileitis is one of the less frequent localizations among joint
      infections, we decided to review 9 cases in a retrospective study of 5 females
      and 4 males, aged between 22 and 60 years old. None had a clinically predisposing
      condition. The initiating factor was gynecologic-obstetric in 4 women, the
      irruption of the skin barrier in 3 cases and finally in one case the infection
      reached the joint through the psoas muscle. Fever and lumbar pain were present in
      all cases and allowed diagnostic orientation. Radiologic and centellographic
      alterations were useful for clinical confirmation. An articular biopsypunction
      was performed in 4 cases, while in the other 5 cases the clinical and radiologic
      features and the bacteriologic positivity in the blood cultures were enough
      criteria for diagnosis. The bacteriologic findings were Staphylococcus aureus (4
      cases), Streptococcus group A beta hemolitico (1 case), Staphylococcus coagulase
      negative (1 case), Streptococcus agalactiae (1 case), Proteus mirabilis (2
      cases). Eight out of 9 patients were treated with a B-lactamic and aminoglycoside
      association. One patient received her treatment per os, with quinolones. Six
      patients recovered, 2 died and one needed to be sent to another hospital.

PMID- 7565045
TI  - [Discordance between CD4 values obtained by flow cytometry or by microscopy in
      HIV infected hemophiliac patients].

PMID- 7565047
TI  - Familial dwarfism and painful muscle spasms.
AB  - We report a family with a disorder characterized by limbs and truncal undulating
      painful muscle spasms, short stature, fine and sparse hair in the scalp, absence
      of body hair, low implanted ears, big nose, pitched voice, enlarged heart
      ventricles and increased fasting glucose levels. Symptoms began in childhood and
      did not progress after the third decade of life. This disorder represents a new
      clinical phenotype among the several forms of dwarfism associated with
      neurological manifestations already described in the literature.

PMID- 7565048
TI  - [Changes in the heme metabolic pathway in diabetic patients].
AB  - In the last decades several authors have observed a frequent association between
      diabetes mellitus and porphyria, mainly porphyria cutanea tarda. In previous
      studies, it has been demonstrated that both d delta d-aminolevulic acid
      dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D), enzymes of the heme
      pathway, are inhibited by high concentrations of glucose in vitro in crude
      preparations of erythrocytes. The activity of these same enzymes was diminished
      in different tissues obtained from streptozotocin induced diabetic mice.
      Therefore, we decided to investigate the incidence of heme metabolism alterations
      in diabetes mellitus in a population of 100 non selected adult patients. The
      activities of erythrocytic ALA-D and PBG-D were measured. Rhodanese, an enzyme of
      the sulfocompounds pathway closely related to the regulation of heme
      biosynthesis, was also studied. Urine porphyrin content as well as the
      chromatographic pattern of esterified porphyrins were determined. ALA-D and PBG-D
      activities were diminished in diabetic patients (40% and 20% respectively), while
      rhodanese was only slightly increased (Fig. 1). ALA-D activity was subnormal in a
      92% of the complete diabetic population, while PBG-D activity was less than
      normal in a 79% of the same population. No significative differences between
      enzymic activities were observed in the groups insulin and non-insulin dependent
      (Fig. 3). Urine porphyrin content was increased in 5% of the diabetic population.
      Chromatographic pattern of urinary porphyrins was notably altered in diabetic
      patients irrespectively of their porphyrin content (Fig. 4), suggesting an
      alteration in the enzyme uroporphyrinogen decarboxylase resembling the primary
      enzymic defect observed in porphyria cutanea tarda.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7565049
TI  - [Congenital Chagas disease in the city of Santa Fe. Diagnosis and treatment].
AB  - We studied 6123 pregnant women and their 341 newborn (NB), from Santa Fe city, by
      the following serological tests for chagasic infection: Direct Agglutination with
      and without 2-mercaptoethanol, Indirect Hemagglutination and Indirect
      Immunofluorescence test, and by identification of parasites by Fresh drops,
      Strout and/or by Xenodiagnosis. The prevalence of seropositivity found in
      pregnant women was of 14.62% with a 73% of migratory history. The parasitological
      studies yielded 9/341 incidence of transplacentary infection. Clinical
      examinations were made in the infected newborn (NB). They were treated with
      Benznidazol or Nifurtimox, and post-treatment evolution was evaluated. We
      registered connatal infection in twin-brothers. Brothers/sisters (siblings) of
      infected NB were also studied. Some of them were seropositive and the others
      seronegative. Results here obtained show that this way of transmission is
      important, and should be considered even in low endemicity areas. The
      parasitological assays proved to be decisive for the NB infection diagnosis
      (Table 1). The serological assays enabled us to follow the non-infected NB up to
      their negativization. A 6 month follow-up is recommended. It is impossible to
      define only one clinical outline because both symptomatic and asymptomatic
      infected NB may be found with gestational age at term and pre-term and when born
      with a weight above or below 2000 g. We obtained parasitological and serological
      negativization in all cases. The chagasic pregnant woman does not necessarily
      transmit the infection to all her descendents. Only 2.64% are infected. It is
      possible to systematize the diagnosis without extra resources beyond the usual
      ones.

PMID- 7565050
TI  - [Early gastric cancer as a metachronic or synchronic tumor. Report of 6 cases].
AB  - Through a period of 16 years, 108 cases of early gastric cancer (EGC) were
      diagnosed at Hospital Mexico, a leading teaching hospital of Costa Rica's social
      security system and the University of Costa Rica. It was found that in four
      cases, the gastric neoplasia was a second primary tumor, and in the two remaining
      cases, the EGC developed synchronously to another neoplasm. Two of the four
      metachronic EGC were preceded by a uterine cervix neoplasm on stage lla; the
      third one was preceded by a breast adenocarcinoma, and the fourth one by a larynx
      cancer in a heavy male smoker. The treatment received for the first cancer was
      radiation therapy only, except for the breast cancer patient in whom surgery was
      employed as well. One of the patients with uterine cervix cancer developed an
      epidermoid bronchogenic cancer 17 years after the first tumor and 8 years after
      her EGC. In the two male patients with synchro tumors, the EGC developed together
      with a squasmous cell carcinoma of esophagus, and in the remaining one the EGC
      appeared simultaneously with a peritoneal mesothelioma. It is important to
      emphasize the presence of radiation therapy in the metachronous tumors, as well
      as the antecedent of smoking in the patient with three primary cancers, the
      esophagus one, and the larynx cancer patient.

PMID- 7565051
TI  - [Pseudohypoparathyroidism].
AB  - A 5 year old boy with normal phenotype and normal renal function presented
      tetany. Hypocalcemia and hyperphosphatemia, with increased serum levels of
      parathyroid hormone (PTH) were detected in serial measurements.
      Pseudohypoparathyroidism was diagnosed. This disease presents the biochemical
      abnormalities of hypoparathyroidism (hypocalcemia, hyperphosphatemia) with
      peripheral resistance to PTH activity. The patient was treated effectively with
      calcium and vitamin D supplements. The causes of hypocalcemia related to
      parathyroid gland activity are reviewed and the physiopathology of
      pseudohypoparathyroidism is described.

PMID- 7565052
TI  - [Febrile syndrome: myocarditis and brucellosis].
AB  - A 20 year-old white man was admitted with fever and weight loss since 60 days
      previous to his admission and cardiac failure (functional class IV). The heart
      was enlarged in the echocardiographic examination without valvular involvement.
      Liver biopsy showed granulomatous hepatitis with a necrosis focus. The patient
      was treated with a combination of venous dilators and digital. Serum
      agglutination test for Brucella showed a titer of 1/250, and complement fixation
      1/40. Seven days later, agglutination titer was 1/4000. He was treated with
      rifampin and trimethoprimsulfametoxazol. He got better; fever disappeared, and
      the signs of cardiac failure improved. Brucellosic myocarditis is an uncommon
      complication of brucellosis in the absence of endocarditis. In our knowledge,
      this case would be the first reported in Argentina and the third in adult
      patients out of the five cases reported worldwide.

PMID- 7565053
TI  - [Unexpected cryptococcosis and AIDS in an elderly patient].

PMID- 7565055
TI  - [Use of polymerase chain reaction (PCR) in oncohematology. Detection of minimal
      residual disease].
AB  - The early detection of clonogenic cells able to survive cytotoxic therapy and to
      initiate a neoplastic process, defined as Minimal Residual Disease (MRD),
      represents a major objective for the development of new and more sensitive
      diagnostic methods. The cloning of different chromosomal translocations along
      with the application of the Polymerase Chain Reaction (PCR) technique has allowed
      the characterization of various hematological disorders at the molecular level.
      This approach has led to the development of PCR based assays able to detect a
      minimum number of malignant cells with very high specificity. In the present
      paper we discuss the use of PCR and its value as a predictor for relapse in
      lymphomas, chronic myelogenous leukemia and acute promyelocytic leukemia,
      characterized by the t(14;18) t(9;22) and t(15;17) translocations, respectively.

PMID- 7565054
TI  - [Hematologic neoplasms and pregnancy].
AB  - Hematologic neoplasms diagnosed during pregnancy, present significant
      difficulties in patient management. Besides the strictly medical facts, moral,
      ethical and religious issues should be strongly considered. For the optimal
      management of individual situations an integrated multidisciplinary approach is
      mandatory. Hodgkin's disease, acute leukemias, non Hodgkin's lymphoma and less
      frequently chronic myelogenous leukemia have been reported in pregnant women.
      Curative treatment for most of these diseases include intensive chemotherapy
      regimens. Potential damage to the fetus is a major concern, due to the
      teratogenic effects of antimetabolites, alkylating agents and radiation therapy.
      Effect of pregnancy in each of these neoplasms is discussed. Although some rules
      of management exist, dangerous generalizations should be avoided. Particular
      obstetric considerations such as timing of delivery, and therapeutic abortion
      should be carried out on an individual basis. The emotional impact of the
      situation must not be underestimated.

PMID- 7565056
TI  - [What was the cause of Oscar Wilde's death?].

PMID- 7565057
TI  - [Ethical problems in medical practice].

PMID- 7565058
TI  - [Mildly dilated congestive myocardiopathy. Unusual case of dilated
      myocardiopathy].

PMID- 7565060
TI  - [The so-called prions].

PMID- 7565059
TI  - [Gene of polycystic renal diseases: point of arrival or departure?].

PMID- 7565062
TI  - [Estimate of the number of persons with Chagas disease in Argentina].

PMID- 7565061
TI  - [Biological markers of diagnostic value in Ewing's sarcoma: the use of antibodies
      against the antigen p30/32 MIC2, called 013].

PMID- 7565063
TI  - [Actuarial survival analysis of patients in dialysis].
AB  - The survival rate of our end stage renal disease (ESRD) population was calculated
      by means of actuarial survival curves. A total of 167 patients undergoing
      hemodialysis or CAPD during the 1977-1991 period were studied. They had been
      treated and closely followed for at least three months. Mean age for starting
      dialysis was 40.6 +/- 17 years; 107 (64%) were males and 60 (36%) females.
      Glomerulonephritis (25%), diabetes (14%) and nephroangiosclerosis (12%) were the
      primary causes of ESRD. Survival rates were analysed by actuarial curves as
      designed by Kaplan and Meier. Statistical significance between curves was
      calculated with the Log Rank test. The level of significance considered was below
      0.05. Multivariate analysis of survival was performed using the Cox proportional
      hazards regression model. Survival rates were in all cases expressed for the 1
      degree, 5 degree and 10 degree year. They were for the whole group of 89%, 63%,
      and 38% respectively. When analysed according to their age: those under 30 years;
      between 30 and 50 and over 50 years old (at time to start dialysis); survival
      rates were of 97%, 86%, and 81% for the first group; 89%, 66% and 29% for the
      second group, and 85%, 44%, and 10% for the third group. Significant differences
      were found between the first and second group (p < 0.025); the first and the
      third group (p < 0.001) and second and third group (p < 0.001) (Fig. 4).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7565066
TI  - Bone metabolism and osteopenia in eating disorders.
AB  - Bone loss is a potentially debilitating condition in women with eating disorders.
      Complications may include failure to achieve peak bone mass, increased risk of
      premature fractures, and inability to reach the height potential. We therefore
      conducted a comprehensive evaluation of 58 women with anorexia nervosa (AN),
      bulimia (BUL) and anorexia/bulimia (AB), comparing bone mineral density (BMD) to
      physical parameters, biochemical indices, and markers for bone formation and
      resorption. BMDs were significantly lower in patients with AN than in those with
      AB and BUL, and overt osteopenia was uncommon in AB and BUL. Hypercortisolism was
      the best laboratory marker to assess the risk of osteopenia in patients with AN.
      However, there were no associated changes in bone formation or resorption
      parameters. No direct correlation was found between BMD and body mass index,
      estrogen deficiency, tubular reabsorption of phosphorus, serum vitamin D, PTH,
      BGP, or alkaline phosphatase levels. Although the prognosis for complete recovery
      to normal BMD is poor, treatment of the underlying depressive disorder,
      improvement in nutrition with increased weight, and spontaneous resumption of
      menses are associated with restoring bone health.

PMID- 7565065
TI  - Polyarteritis nodosa related to hepatitis B virus. A prospective study with long
      term observation of 41 patients.
AB  - Hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) is a rare disease
      whose frequency has been decreasing over the past 10 years. We evaluated 41
      patients with HBV-related PAN to determine the circumstances leading to
      infection, the clinical features of vasculitis, the prognostic factors, and the
      response to therapy. Most patients were first treated briefly with
      corticosteroids, and all were included in 2 nonrandomized prospective therapeutic
      trials of an antiviral agent (35 patients with vidarabine, 6 patients with
      interferon-alpha 2b) and plasma exchanges. The mean duration of follow-up was
      69.6 +/- 44.8 months. At the end of the study, 21 (51.2%) patients had
      seroconverted to anti-HBeAb and 10 (24.4%) also had seroconverted to anti-HBsAb.
      In all, 23 (56%) patients no longer expressed serologic evidence of HBV
      replication. All 33 (80.5%) patients still alive at the end of follow-up
      recovered from PAN. Nineteen also recovered from HBV infection and were
      considered to be cured; 13 patients had persistent HBV infection and were
      considered to be in clinical recovery; and 1 patient was in remission, maintained
      with steroid therapy. Eight patients died during the study period; 3 deaths were
      directly attributable to PAN. HBV-related PAN is an acute disease, occurring
      shortly after infection and sharing the characteristics of classic PAN. It is not
      an antineutrophil cytoplasm antibodies (ANCA)-mediated vasculitis. The outcome
      was good for patients treated with short-term steroid therapy, antiviral agents,
      and plasma exchanges. We propose this protocol as the first treatment for HBV
      related PAN, because it surpasses the conventional treatment with corticosteroids
      and cyclophosphamide, which facilitates viral replication and the development of
      chronic HBV infection.

PMID- 7565064
TI  - Silica-associated connective tissue disease. A study of 24 cases.
AB  - We prospectively studied all patients hospitalized for connective tissue disease
      (CTD) in our French rheumatology clinic from January 1979 to December 1989. Our
      aims were 1) to determine if CTDs associated with occupational exposure to silica
      (Si) are currently observed in a rheumatology clinic, and, if so, 2) to describe
      the major features of Si-associated CTD, and 3) to specify which individuals are
      affected by Si-associated CTD. Patients were divided into 2 groups based on their
      responses to a questionnaire: those who had been exposed to Si, and those who had
      no occupational exposure to Si. Among the 764 patients with CTD studied, 24 (3%)
      were patients with Si-associated CTD and 740 (97%) were patients with non-Si
      associated CTD. The sex ratio between the 2 groups was significantly different
      with a high frequency of men and of immigrants in the Si-associated CTD group.
      Two thirds of the patients exposed to Si were male miners or sandblasters, but
      the other third had more unusual exposures to Si, which may involve members of
      all socio-economics sectors and both sexes, such as sculpture or exposure to
      abrasive powders. Progressive systemic sclerosis (PSS) was significantly more
      prevalent in the Si-associated CTD group. This group also consisted of patients
      with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE),
      dermatomyositis (DM), and other autoimmune diseases. Si-associated CTD was
      characterized by the frequency of radiologic lung fibrosis, impaired pulmonary
      function tests, secondary Sjogren syndrome, and antinuclear antibodies. The
      number of mineral particles and crystalline Si content were raised in all the
      bronchoalveolar lavage specimens of Si-exposed patients but in none of those of
      nonexposed patients. In some cases of Si-associated CTD, the disease was
      reversible after early cessation of Si exposure. Epidemiologic studies are
      required to confirm our hypothesis that not only PSS and RA but also SLE and DM
      are associated with occupational exposure to Si. Pending such results, exposure
      to Si should be sought in the history of any patient with CTD, especially in a
      male patient with pulmonary signs, and if present, exposure should be stopped. In
      the meantime, steps should be taken to ensure that workers exposed to Si in all
      environments have adequate protection.

PMID- 7565067
TI  - Spontaneous periodic hypothermia.
AB  - Spontaneous periodic hypothermia is a rare syndrome of recurrent, centrally
      mediated hypothermia without an identifiable systemic cause or brain lesion. Most
      patients defend a temporarily lowered temperature "set point" during episodes of
      hypothermia, despite manifesting many well-known systemic consequences of core
      temperature hypothermia. No case of death directly attributable to an episode of
      spontaneous periodic hypothermia has been reported, although many of the serious
      systemic effects of hypothermia have been documented in these cases, so it is not
      unlikely that death may occur. The syndrome's cause, and that of Shapiro
      syndrome, remains unknown. Pharmacologic trials to date have been only modestly
      successful. Anticonvulsant agents, clonidine, and cyproheptadine appear the most
      likely to succeed, with cyproheptadine being a reasonable first choice. Given
      that the term "spontaneous periodic hypothermia" describes a syndrome, and not a
      pathophysiologic mechanism, it is likely to encompass a common eventuality,
      arrived at via several different pathways. One can postulate mechanisms such as
      structural abnormalities, trauma, infection, irritation, and degeneration
      involving strategic locations which create a focus for epileptic or other
      periodic dysfunction whose scope involves the centers for thermoregulation. The
      existence of 2 distinct, oppositional thermoregulatory centers would allow for
      speculation of similar mechanisms accounting for cases of both periodic hypo- and
      hyperthermia (61). Postmortem data regarding the hypothalamic and surrounding
      areas from future cases of Shapiro syndrome and spontaneous periodic hypothermia
      would be of great interest. Further, more sensitive in vivo testing methods are
      clearly needed. The role of PET or single photon emission computed tomography
      (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m
      HMPAO) performed acutely during an episode remains to be characterized (64, 103,
      105). The term "diencephalic epilepsy" may in fact be accurate, given the
      periodic episodes of the case presented here and similar cases resulting from non
      generalized seizure activity, with or without an underlying predisposing lesion.
      The label diencephalic epilepsy has been merely speculative so far, however, as
      definitive evidence of seizure activity has not been documented. Further, it is
      expected that the descriptive terms "spontaneous periodic hypothermia" and
      "episodic spontaneous hypothermia with hyperhidrosis" will outlive their
      usefulness as researchers gain greater understanding of this syndrome, and be
      replaced with a more pathophysiologically meaningful nomenclature.

PMID- 7565068
TI  - Long-term outcome after whiplash injury. A 2-year follow-up considering features
      of injury mechanism and somatic, radiologic, and psychosocial findings.
AB  - With the increased incidence of whiplash injury following the introduction of
      compulsory car seat belts, a large number of reports have dealt with the
      aftermath of this condition. Previous studies, however, focused on somatic
      symptoms on the one hand or considered only psychological or neuropsychological
      variables on the other hand, often in loosely defined or selected groups of
      patients. No study so far has analyzed the long-term outcome in a nonselected
      group of patients using a clear injury definition considering patient history;
      somatic, radiologic, and neuropsychological findings; and features of the injury
      mechanisms assessed soon after trauma and during follow-up. the present
      investigation was designed to assess these combined factors. According to a
      strict definition of whiplash injury, we assessed a consecutive nonselected
      sample of 117 patients with recent injury who had similar sociocultural and
      educational backgrounds. The patients had been in automobile crashes and were all
      equally covered by accident insurance according to the country-wide scheme.
      Initial examination was performed 7.2 +/- 4.2 days after trauma, and follow-up
      examinations 3, 6, 12, and 24 months later. At baseline, features of injury
      mechanism, subjective complaints, and different aspects of patient history were
      documented and cervical spine X rays performed. At all examinations patients
      underwent neurologic examination and cognitive and psychosocial factor
      assessment. At 2 years, patients were divided into symptomatic and asymptomatic
      groups and then compared with regard to the initial findings. In addition,
      symptomatic patients who were disabled at the 2-year follow-up examination and
      symptomatic patients not disabled (that is, they were able to work at the
      pretraumatic level) were compared regarding initial and 2-year findings. At 2
      years, 18% of patients still had injury-related symptoms. With regard to baseline
      findings the following significant differences were found: Symptomatic patients
      were older, had higher incidence of rotated or inclined head position at the time
      of impact, had higher prevalence of pretraumatic headache, showed higher
      intensity of initial neck pain and headache, complained of a greater number of
      symptoms, had a higher incidence of symptoms of radicular deficit and higher
      average scores on a multiple symptom analysis, and displayed more degenerative
      signs (osteoarthrosis) on X ray. In addition, symptomatic patients scored higher
      with regard to impaired well-being and performed worse on tasks of attentional
      functioning and showed more concern with regard to long-term suffering and
      disability.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7565070
TI  - [Examination of health effects from exposure to metallic mercury in workers
      employed in production of chlorine and aldehyde. II. Assessment of kidney
      lesions].
AB  - A group under study embraced 73 workers involved in the production of acetic
      aldehyde, 74 workers of the department of chlorine and 13 retired workers with
      past poisoning by mercury. The control group consisted of 40 persons.
      Examinations performed in all subjects were designed mainly to assess the kidney
      lesions. The following results were obtained: Simple markers of kidney lesions
      (functions) such as urine standard examination, concentration of creatinine and
      glomerular filtration did not reveal clear-cut symptoms of metallic mercury
      nephrotoxic effect. In persons exposed to mercury an increased activity of
      lysosomal enzyme--beta-N-acetylglucosaminidase (beta-NAG) in urine was found. The
      activity of this enzyme showed correlation with actual mercury excretion in
      urine. A lack of correlation between beta-NAG activity and the index of cumulated
      urine excretion of mercury and the duration of exposure to mercury as well as low
      activity of this enzyme in the group of retired workers and pensioners with past
      poisoning by mercury suggest that the increase of beta-NAG activity is an
      reversible phenomenon. The value of determination of beta-2-microglobulin
      concentration in urine in persons currently exposed to mercury is doubtful
      because of the degradation of this protein resulting from urine acidification.
      The prolongation of secretory and excretory phase found in the renovasographic
      examination indicates the value of this method in the evaluation of kidney lesion
      in persons exposed to metallic mercury.

PMID- 7565069
TI  - The science of whiplash.

PMID- 7565074
TI  - [Transformation of ownership in occupational health services].
AB  - The process of the ownership transformation in occupational health services began
      in 1991. At that time Section X of the Labour Code was amended by introducing the
      system according to which employers participate in the costs of organization of
      occupational health services and other expenditure involved in health care of
      their workers. In addition, the Health Service Institutions Act of August 30,
      1991 prepared the ground for the organization of health care units by various
      economic subjects including employers if the responsibility for taking care of
      workers' health is included in the statute of such a unit. From 1992 the process
      of the ownership transformation in occupational health services has started to
      progress. New non-public occupational health care units began to be established
      mainly by numerous institutions. In 1992 already 62 units were set up in six
      voivodships (provinces). In 1993 their number increased to 306 and they were
      located in 20 voivodships. The analysis of facilities and activities of non
      public occupational health care units, based on the data available, indicated,
      however, that the process of the ownership transformation has not satisfied to
      date all expectations concerning the change in the quality of services rendered.
      Although these new units have not been established by the state administration
      their activities show similar week points as those belonging to the old system of
      industrial health services. Still treatment accounts for 80% of their activities,
      secondary care represents almost the same standard as in the public health
      service sector.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565072
TI  - [Renin-angiotensin-aldosterone system in chronic poisoning of rats with lead and
      cadmium].
AB  - The aim of the study was to investigate the impact of the chronic, single and
      combined exposure to lead and cadmium on renin-angiotensin-aldosterone system in
      rats. Experiments were performed on male Buffalo rats which were intragastrically
      administered of lead acetate in doses of 35 mg Pb/kg body weight once a week or
      in doses of 70 mg Pb/kg body wt. twice a week and/or cadmium chloride in doses of
      20 mg Cd/kg body wt. once a week for a period of seven weeks. One day after the
      feeding was over, the following parameters were measured: plasma renin activity,
      activity of angiotensin converting enzyme, serum concentration of angiotensin II
      and aldosterone. Metal content (lead, cadmium and zinc) in blood, kidneys and
      brain was determined by means of atomic absorption spectrophotometry. No clinical
      signs of lead or cadmium toxicity effects were observed. Rats poisoned with
      different doses of lead displayed no changes in renin-angiotensin system. In
      comparison to controls, in rats poisoned with cadmium, decrease in the plasma
      renin activity, serum angiotensin II and aldosterone concentrations were
      observed, but it was associated with unchanged activity of angiotensin converting
      enzyme. The decrease in plasma renin activity depended on cadmium levels in
      blood. In comparison to rats given cadmium, in rats treated with cadmium and lead
      together the inhibitor of the renin-angiotensin-aldosterone systems was weaker,
      although cadmium was used in the same dose.

PMID- 7565071
TI  - [The linear correlation coefficient of serotonin and prolactin concentrations in
      plasma of women chronically exposed to carbon disulfide].
AB  - A group of 70 women, examined clinically, was divided into two even subgroups:
      subgroup I--controls, aged 49.8 +/- 3.2 years, non-exposed to carbon disulfide
      (CS2), and subgroup II, aged 43.6 +/- 1.7 years chronically exposed to CS2 in
      concentration of 9.36--23.4 mg/m3. The concentration of CS2 was measured using Mc
      Cammon's method, concentration of serotonin in plasma by employing the
      colorimetric method according to Manuchin and the radioimmunological method was
      applied in measuring the prolactin concentration. Student-t test and Pearson's
      linear correlation coefficient "C" were used for the statistical analysis. It was
      found that in women exposed to CS2 serotonin and prolactin concentrations were
      significantly higher (p < 0.001). The linear correlation between serotonin and
      prolactin concentrations was also significantly positive (r = 0.44; p 0.01) in
      women expose to carbon disulfide.

PMID- 7565075
TI  - [Is heavy physical work a risk factor for ischemic heart disease?].
AB  - The authors presents current data on the relationship between the level of
      physical activity and the incidence of ischaemic heart disease. It was stressed
      that occupational and non-occupational physical activity should be considered
      differently in view of the fact that the most common physical effort at work
      applies to a limited group of muscles with a high component of static effort.
      Therefore it is not optimal from the training point of view, and affects
      negatively the circulatory system. Attention is also turned to the health
      consequences of a psycho-social load related to work, education and social
      status. In conclusion it is stated that blue collar workers become a group of an
      increased risk of ischaemic heart disease because of accumulation of all negative
      factors: heavy work, static effort, insufficient physical activity outside the
      work and limited health conductive life style, inadequate and rapidly lowering
      physical fitness, usually work at high speed and difficulties in controlling own
      situation. Therefore, special preventive programs indicating how to eliminate
      unhealthy behaviour and promote life style which reduces the risk of ischaemic
      heart disease should be developed.

PMID- 7565073
TI  - [Causes and consequences of maxillofacial trauma due to occupational accidents in
      the north-east region of Poland].

PMID- 7565076
TI  - [Oxidative stress as a basic mechanism of the carcinogenic effect of man made
      mineral fibers on the human body].
AB  - Man made mineral fibres have been recently introduced into industry as asbestos
      exchangers due to their much less harmful effect on workers' health. However, in
      1988 IARC classified such mineral fibres as glass wool, rock wool and slag wool
      as probably carcinogenic for a man. The mechanism how MMMF may induce the
      carcinogenic process remains still unclear. It is assumed that the involvement of
      these fibres in the production of free oxygenic radicals is one of the most
      important factors contributing to the initiation of this process by MMMF. In the
      condition where free oxygenic radicals are produced very fast, the cell is
      exposed to an oxidative stress. The DNA damage is an important consequence of the
      oxidative stress. New oxygenic radicals may modify DNA and lead to mutation and
      finally they may contribute to the occurrence of neoplastic cells. OH is an
      oxygenic radical which most often damages DNA. It was also indicated that MMMF
      contributes to the increase of the number and activity of neutrophilic
      granulocytes and macrophages. The appearance of MMMF fraction in granulocyte
      results in an increased production of free oxygenic radicals which may damage DNA
      of epithelial cells. Experimental studies indicate that the production of free
      oxygenic radicals by neutrophilic granulocytes and macrophages activated by MMMF
      increases under the influence of chemicals embodied in tobacco smoke. The fibres
      when combined with tobacco smoke enlarge the number of DNA damages.
      Notwithstanding the information on a possible induction of a carcinogenic process
      by MMMF, epidemiological studies indicate that MMMF shows much less carcinogenic
      hazard than asbestos fibres.

PMID- 7565078
TI  - [Information sources on carcinogenic agents].
AB  - This work comprises lists of publications and computer data bases available at
      the Scientific Information Department, The Nofer Institute of Occupational
      Medicine, Lodz, Poland, containing information on cancer risks resulting from
      exposure to carcinogenic agents. The following publications have been described:
      IARC Monographs on the Evaluation of Carcinogenic Risk to Humans; Official lists
      of carcinogens valid in individual countries; a periodical--Survey of compounds
      which have been tested for carcinogenic activity; a guide--The Annual Report on
      Carcinogens, a series on Carcinogens in the Occupational Environment, comprising
      Information Cards and Monographs; a guide on Carcinogenic Agents, and computer
      databases, including the INCAR, IRIS, IRPTC, RTECS CHEMINFO factual databases and
      the CANCER-CD, MEDLINE, TOXLINE, NIOSHTIC and MEDIP bibliographic (or reference)
      databases. The presented publications and databases may prove helpful in
      searching for data on identifying and preventing the adverse health effects of
      environmental and occupational exposure to carcinogens.

PMID- 7565079
TI  - [About life, work and health problems of fishermen employed by PPP and H "Dalmor"
      SA., fishing at the Sea of Okhotsk].

PMID- 7565077
TI  - [Myocardial infarction as a work-related occurrence].
AB  - An accident is a work-related event caused by an external factor. The aim of this
      work is to present a cause-effect relationship between myocardial infarction and
      working conditions. An attitude of the Supreme Court to the question of
      certification highlighting key issues and facilitating the understanding of the
      problem is also presented. Myocardial infarction as a work-related accident is an
      issue of both law and medicine, and particularly, occupational medicine that will
      have to deal and solve this problem in the near future.

PMID- 7565080
TI  - Branched-chain fatty acids: the case for a novel form of cell-cell signalling
      during Myxococcus xanthus development.
AB  - The esg locus is required for the formation of multicellular fruiting bodies and
      spores by the developmental bacterium Myxococcus xanthus. Studies have suggested
      that esg mutants are defective in the production of an essential signal (E
      signal) used in cell-cell communication and that E-signalling is required for the
      expression of many developmental genes. Recently we have determined that the esg
      locus encodes components of a branched-chain keto acid dehydrogenase, a
      multienzyme complex involved in branched-chain amino acid metabolism in many
      bacteria and higher organisms. During vegetative growth in M. xanthus, this
      enzyme complex appears to participate in the production of the branched-chain
      fatty acids found in this organism. M. xanthus fatty acids (including the
      branched-chain fatty acids) have been observed to have a variety of effects on
      developing cells. These effects include: (i) the lysis of M. xanthus cells
      (autocide activity), (ii) acceleration of the rate of sporulation and (iii)
      rescue of sporulation by certain development-defective mutants. These and other
      results suggest a model in which the branched-chain fatty acids, synthesized
      during growth, are released from cellular phospholipid by a developmentally
      regulated phospholipase during fruiting-body formation. This model proposes that
      one or more of the branched-chain fatty acids that are released constitutes the E
      signal which must be transmitted between cells to complete M. xanthus
      development.

PMID- 7565081
TI  - The esg locus of Myxococcus xanthus encodes the E1 alpha and E1 beta subunits of
      a branched-chain keto acid dehydrogenase.
AB  - The esg locus of Myxococcus xanthus appears to control the production of a signal
      that must be transmitted between cells for the completion of multicellular
      development. DNA sequence analysis suggested that the esg locus encodes the E1
      decarboxylase (composed of E1 alpha and E1 beta subunits) of a branched-chain
      keto acid dehydrogenase (BCKAD) that is involved in branched-chain amino acid
      (BCAA) metabolism. The properties of an esg::Tn5 insertion mutant supported this
      conclusion. These properties include: (i) the growth yield of the mutant was
      reduced with increasing concentrations of the BCAAs in the medium while the
      growth yield of wild-type cells increased, (ii) mutant extracts were deficient in
      BCKAD activity, and (iii) growth of the mutant in media with short branched-chain
      fatty acids related to the expected products of the BCKAD helped to correct the
      mutant defects in growth, pigmentation and development. The esg BCKAD appears to
      be involved in the synthesis of long branched-chain fatty acids since the mutant
      contained reduced levels of this class of compounds. Our results are consistent
      with a model in which the esg-encoded enzyme is involved in the synthesis of
      branched-chain fatty acids during vegetative growth, and these compounds are used
      later in cell-cell signalling during development.

PMID- 7565082
TI  - Low-molecular-weight succinoglycan is predominantly produced by Rhizobium
      meliloti strains carrying a mutated ExoP protein characterized by a periplasmic N
      terminal domain and a missing C-terminal domain.
AB  - The membrane topology of the Rhizobium meliloti 2011 ExoP protein involved in
      polymerization and export of succinoglycan was analysed by translational fusions
      of lacZ and phoA reporter genes to the exoP gene. Based on this analysis, the
      ExoP protein could be divided into an N-terminal domain mainly located in the
      periplasmic space and a C-terminal domain located in the cytoplasm. Whereas the C
      terminal domain of ExoP is characterized by a potential nucleotide-binding motif,
      the N-terminal ExoP domain contains the sequence motif 'PX2PX4SPKX11GXMXG', which
      is also present in proteins involved in the determination of O-antigen chain
      length. R. meliloti strains carrying mutated exoP* genes, exclusively encoding
      the N-terminal ExoP domain, produced a reduced amount of succinoglycan. This
      reduction could be suppressed by a mutation in the regulatory gene exoR. The
      ratio of low-molecular-weight to high-molecular-weight succinoglycan was
      significantly increased in the exoP* mutant strain. In the exoP*/exoR mutant
      strain only low-molecular-weight succinoglycan could be detected. Based on
      sequence homologies and similar hydropathic profiles, the N-terminal domain of
      ExoP was proposed to be a member of a protein family thought to be involved in
      polysaccharide chain-length determination.

PMID- 7565083
TI  - Activation of the transcriptional regulator XylR of Pseudomonas putida by release
      of repression between functional domains.
AB  - In the presence of toluene, xylenes and other structural analogues, the
      regulatory protein XylR, of the family of transcriptional regulators which act in
      concert with the sigma 54 factor, activate the promoter Pu of the TOL (toluene
      degradation) plasmid pWWO of Pseudomonas putida. Amino acid changes Val-219-Asp
      and Ala-220-Pro, introducing a proline kink at the hinge region between the N
      terminal A domain and the central portion of XylR, resulted in a semi
      constitutive phenotype which mimicked the activating effect of aromatic inducers.
      This phenotype was further exacerbated by inserting extra amino acid residues
      within the same inter-domain region. A truncated XylR protein devoid of the
      signal-receiving, amino-terminal portion of the protein stimulated the cognate
      promoter Pu at high levels independently of inducer addition, both in Escherichia
      coli and in Pseudomonas putida. Replacement of the amino-terminal domain by a
      heterologous peptide derived from the MS2 virus polymerase resulted in a hybrid
      protein still able to bind DNA to the same extent in vivo as XylR, but unable to
      stimulate transcription. These data indicate that a key event in the activation
      of XylR by toluene/xylenes is the release of the repression caused by the A
      domain of the protein on surfaces located at the central domain of the regulator.

PMID- 7565084
TI  - The genetic basis of colony opacity in Streptococcus pneumoniae: evidence for the
      effect of box elements on the frequency of phenotypic variation.
AB  - Streptococcus pneumoniae undergoes spontaneous phase variation in colony
      morphology. Differences in colony opacity have previously been shown to correlate
      with differences in the ability of organisms to colonize the mucosal surface of
      the nasopharynx in an animal model. The genetic basis of opacity variation was
      identified in transformation experiments. A DNA library, from a strain that
      varies at high frequency, was screened to identify a single clone capable of
      transforming a transparent recipient strain which varies at low frequency to an
      opaque phenotype. Analysis of this opacity locus revealed two genes, glpD and
      glpF, with similarity to genes required for glycerol metabolism in other
      bacteria. Following the pneumococcal glpF, repetitive intergenic elements, boxes
      A and C, were identified. These stem-loop-forming elements were not present in
      the same locus of the recipient strain. Although not required for phase variation
      in colony opacity, the box element was necessary for expression of phase
      variation at high frequency. Introduction of the box elements during
      transformation affected colony morphology, possibly by altering expression of a
      putative regulatory gene downstream from the box element. Mutagenesis within this
      region confirmed the contribution of the putative regulatory gene to the
      expression of colony opacity. Growth characteristics of strains generated in this
      study provide additional evidence for an association of differences in cell wall
      autolysis and variation in colony opacity.

PMID- 7565085
TI  - A family of bacteriocin ABC transporters carry out proteolytic processing of
      their substrates concomitant with export.
AB  - Lantibiotic and non-lantibiotic bacteriocins are synthesized as precursor
      peptides containing N-terminal extensions (leader peptides) which are cleaved off
      during maturation. Most non-lantibiotics and also some lantibiotics have leader
      peptides of the so-called double-glycine type. These leader peptides share
      consensus sequences and also a common processing site with two conserved glycine
      residues in positions -1 and -2. The double-glycine-type leader peptides are
      unrelated to the N-terminal signal sequences which direct proteins across the
      cytoplasmic membrane via the sec pathway. Their processing sites are also
      different from typical signal peptidase cleavage sites, suggesting that a
      different processing enzyme is involved. Peptide bacteriocins are exported across
      the cytoplasmic membrane by a dedicated ATP-binding cassette (ABC) transporter.
      Here we show that the ABC transporter is the maturation protease and that its
      proteolytic domain resides in the N-terminal part of the protein. This result
      demonstrates that the ABC transporter has a dual function: (i) removal of the
      leader peptide from its substrate, and (ii) translocation of its substrate across
      the cytoplasmic membrane. This represents a novel strategy for secretion of
      bacterial proteins.

PMID- 7565086
TI  - Genetic studies reveal that myristoylCoA:protein N-myristoyltransferase is an
      essential enzyme in Candida albicans.
AB  - MyristoylCoA:protein N-myristoyltransferase (Nmt) catalyses the co-translational,
      covalent attachment of myristate (C14:0) to the amino-terminal glycine residue of
      a number of eukaryotic proteins involved in cellular growth and signal
      transduction. The NMT1 gene is essential for vegetative growth of Saccharomyces
      cerevisiae. Studies were carried out to determine if Nmt is also essential for
      vegetative growth of the pathogenic fungus Candida albicans. A strain of C.
      albicans was constructed in which one copy of NMT was partially deleted and
      disrupted. A Gly-447-->Asp mutation was introduced into the second NMT allele.
      This mutation produced marked reductions in catalytic efficiency at 24 and 37
      degrees C, as judged by in vitro kinetic studies of the wild-type and mutant
      enzymes which had been expressed in, and purified from, Escherichia coli. The
      growth characteristics of isogenic NMT/NMT, NMT/delta nmt, and nmt delta/nmtG447D
      C. albicans strains were assessed under a variety of conditions. Only the nmt
      delta/nmtG447D strain required myristate for growth. This was true at both 24 and
      37 degrees C. Palmitate could not substitute for myristate. Incubation of nmt
      delta/nmtG447D cells at 37 degrees C in the absence of myristate resulted in cell
      death as observed by the inability to form colonies on media supplemented with
      500 microM myristate. Studies in an immunosuppressed-mouse model of C. albicans
      infection revealed that the NMT/delta nmt strain produced 100% lethality within 7
      d after intravenous administration while the isogenic nmt delta/nmtG447G strain
      produced no deaths even after 21 d. These observations establish that Nmt is
      essential for vegetative growth of C. albicans and suggest that inhibitors of
      this acyltransferase may be therapeutically useful fungicidal agents.

PMID- 7565087
TI  - Entry of Listeria monocytogenes into hepatocytes requires expression of inIB, a
      surface protein of the internalin multigene family.
AB  - The intracellular bacterium Listeria monocytogenes can invade several types of
      normally non-phagocytic cells. Entry into cultured epithelial cells requires the
      expression of inIA, the first gene of an operon, comprising two genes: inIA,
      which encodes internalin, an 800-amino-acid protein, and inIB, which encodes a
      630-amino-acid protein. Several genes homologous to inIA are detected in the
      genome of L. monocytogenes; InIB is one of them. We have assessed the role of
      inIB in invasiveness of L. monocytogenes by constructing isogenic chromosomal
      deletion mutants in the inIAB locus. Our findings indicate that: i) inIB is
      required for entry of L. monocytogenes into hepatocytes, but not into intestinal
      epithelial cells; ii) inIB encodes a surface protein; iii) internalin plays a
      role for entry into some hepatocyte cell lines. These results provide the first
      insight into the cell tropism displayed by L. monocytogenes.

PMID- 7565088
TI  - Purification and characterization of LasD: a second staphylolytic proteinase
      produced by Pseudomonas aeruginosa.
AB  - We have previously described studies of a 22 kDa active fragment of the LasA
      proteinase. In follow-up studies of LasA, we have discovered the separate
      existence of a 23 kDa proteinase which shares many of the enzymatic properties of
      LasA, including the ability to lyse heat-killed staphylococci. However, this
      apparent serine proteinase, which we designate LasD, is distinct from the 22 kDa
      active LasA protein for the following reasons: (i) the N-terminal sequence of
      LasD shares no homology with LasA or the LasA precursor sequence; (ii)
      Pseudomonas aeruginosa LasA mutant strains AD1825 and FRD2128 do not produce LasA
      yet produce LasD; and (iii) specific antibodies to each proteinase do not show
      any cross-reactivity. LasD appears to be produced as a 30 kDa protein, which is
      possibly cleaved to produce a 23 kDa active fragment. The purified LasD fragment
      (23 kDa) shows strong staphylolytic activity only at higher pH conditions, while
      LasA exhibits staphylolytic activity over a broad pH range. In addition to their
      ability to cleave at internal diglycine sites, both the LasD and LasA
      endoproteinases efficiently cleave beta-casein.

PMID- 7565089
TI  - Lipopolysaccharides of polymyxin B-resistant mutants of Escherichia coli are
      extensively substituted by 2-aminoethyl pyrophosphate and contain aminoarabinose
      in lipid A.
AB  - Lipopolysaccharides (LPS) of two polymyxin-resistant (pmr) mutants and the
      corresponding parent strain of Escherichia coli were chemically analysed for
      composition and subjected to 31P-NMR (nuclear magnetic resonance) for assessment
      of phosphate substitution. Whereas the saccharide portions, fatty acids, and
      phosphate contents were similar in wild-type and pmr LPS, the latter contained
      two- to threefold higher amounts of 2-aminoethanol. The pmr LPS also contained 4
      amino-4-deoxy-L-arabinopyranose (L-Arap4N), which is normally not a component of
      E. coli LPS. This aminopentose has been assigned to be linked to the 4'-phosphate
      of lipid A. Comparative 31P-NMR analysis of the de-O-acylated LPS of the wild
      type and pmr strains revealed that phosphate groups of the pmr LPS were mainly
      (71-79%) diphosphate diesters, which accounted for only 20% in the wild-type LPS.
      Diphosphate monoesters were virtually nonexistent in the pmr LPS, whereas they
      accounted for 42% of all phosphates in wild-type LPS. In the lipid A of the pmr
      strains, the 4'-phosphate was to a significant degree (35%) substituted by L
      Arap4N, whereas in the wild-type LPS the L-ArapN was absent. In the pmr lipid A,
      2-aminoethanol was completely substituting the glycosidic pyrophosphate but not
      the glycosidic monophosphate, forming a diphosphate diester linkage at this
      position in 40% of lipid A molecules. In the wild-type LPS the glycosidic
      position of lipid A carried mostly unsubstituted monophosphate and pyrophosphate.
      Thus the polymyxin resistance was shown to be associated, along with the
      esterification of the lipid A 4'-monophosphate by aminoarabinose, with extensive
      esterification of diphosphates in LPS by 2-aminoethanol.

PMID- 7565090
TI  - Activation of a temporally regulated Caulobacter promoter by upstream and
      downstream sequence elements.
AB  - The flagellar genes of Caulobacter crescentus are expressed under cell-cycle
      control. Expression is regulated by both flagellar assembly cues and cell-cycle
      events. In this paper we define the sequences required for the expression of the
      flgF operon, a new class of sigma 54 flagellar promoter. This promoter type is
      expressed in the middle portion of the cell cycle and regulates the expression of
      basal-body genes. DNase I footprinting and mutagenesis demonstrates that an
      integration host factor (IHF)-binding site is required for maximal levels of
      transcription of the flgF promoter. In addition to containing a conventional
      upstream enhancer element (RE-1), this promoter is unusual in that it also
      requires sequences (element RE-2) immediately downstream of the transcriptional
      start site for maximal levels of gene expression. Cell-cycle experiments indicate
      that RE-1 and RE-2 contribute equally to the regulation of temporal
      transcription. The presence of two intact elements in the promoter results in a
      fourfold increase in promoter activity compared with a promoter containing only
      one intact element, suggesting that these two elements may function
      synergistically to activate transcription.

PMID- 7565091
TI  - Enhanced secretion through the Shigella flexneri Mxi-Spa translocon leads to
      assembly of extracellular proteins into macromolecular structures.
AB  - Genes required for entry of Shigella flexneri into epithelial cells in vitro are
      clustered in two adjacent loci, one of which encodes secretory proteins, the IpaA
      D proteins, and the other their dedicated secretion apparatus, the Mxi-Spa
      translocon. Ipa secretion, which is induced upon contact of bacteria with
      epithelial cells, is prevented during growth in vitro. Here, we show that ipaB
      and ipaD mutations lead to enhanced secretion of a set of about 15 proteins.
      These extracellular proteins and some Ipas associate in organized structures
      consisting of extended sheets. Growth of the wild-type strain in the presence of
      Congo red is shown to induce protein secretion through the Mxi-Spa translocon.
      Cultures grown to stationary phase in the presence of Congo red contain
      extracellular filaments whose composition and morphology are similar to those
      produced by the hypersecreting ipaB and ipaD mutants.

PMID- 7565092
TI  - Isolation and characterization of genes that promote the expression of inositol
      transporter gene ITR1 in Saccharomyces cerevisiae.
AB  - The expression of many genes of Saccharomyces cerevisiae, such as ITR1, is
      regulated by inositol and choline. In this work, a yeast strain has been
      constructed in which HIS3 expression is controlled by the ITR1 promoter. Using
      this strain, three genes were isolated which, when introduced as multicopies,
      abolish the repression caused by inositol via the ITR1 promoter. Northern blot
      analysis revealed that two of these three genes, designated as DIE1 and DIE2,
      clearly increased the expression of ITR1. DIE2 is more effective for ITR1
      expression than DIE1. Gene-disruption experiments revealed that DIE1 was
      essential for the expression of ITR1 but that DIE2 was not. The sequence of the
      DIE1 gene was shown to be identical to that of INO2 (also called SCS1), which
      encodes a protein required for the expression of INO1. DIE2 is a new gene and is
      capable of encoding 525 amino acid residues with a calculated molecular weight of
      61,789. Experiments involving lacZ fusion genes showed that multicopy DIE2
      resulted in an increase in the expression of both ITR1 and INO1. These results
      strongly suggest that the DIE1 and DIE2 gene products have an important
      regulatory function for gene expression of not only ITR1 but also INO1.

PMID- 7565093
TI  - The Escherichia coli genes sspA and rnk can functionally replace the Pseudomonas
      aeruginosa alginate regulatory gene algR2.
AB  - The algR2 (also known as algQ) gene of Pseudomonas aeruginosa has previously been
      identified as being necessary for alginate production at 37 degrees C. We have
      cloned two genes, from a cosmid library of Escherichia coli, which can restore
      mucoidy to an algR2 mutant of P. aeruginosa. The complementing regions of both
      cosmids were localized by subcloning restriction fragments. One of the E. coli
      genes identified here has not previously been described; we have named this gene
      rnk (regulator of nucleoside diphosphate kinase). It encodes a 14.9 kDa protein
      with no homology to any other protein. The other gene, sspA, is a regulator
      involved in stationary-phase regulation in E. coli. Either gene will restore
      mucoidy to an algR2-deficient strain of P. aeruginosa. AlgR2 has been shown to
      regulate at least two enzymes, succinyl-CoA synthetase (Scs) and nucleoside
      diphosphate kinase (Ndk), which form a complex in P. aeruginosa. When we examined
      the ability of the E. coli analogues to regulate Ndk, we found that rnk but not
      sspA was able to restore Ndk activity to the P. aeruginosa algR2 mutant.
      Furthermore, rnk was able to restore growth of the algR2 mutant in the presence
      of Tween 20, which inhibits other Ndk-like activities.

PMID- 7565094
TI  - Genetic and molecular analysis of a regulatory region of the herbicide 2,4
      dichlorophenoxyacetate catabolic plasmid pJP4.
AB  - In Alcaligenes eutrophus JMP134, pJP4 carries the genes coding for 2,4
      dichlorophenoxyacetate (2,4-D) and 3-chlorobenzoate (3-Cba) degradation plus
      mercury resistance. The plasmid genes specifying 2,4-D and 3-Cba catabolism are
      organized in three operons: tfdA, tfdB, and tfdCDEF. Regulation of these operons
      by two unlinked genes, tfdR and tfdS, has been proposed. Physical and DNA
      sequence analyses revealed that the tfdR and tfdS genes were identical and were
      located within a longer inverted repeat of 1592 bp. Similar stem-loop structures
      were observed among other 2,4-D plasmids. The tfdR gene is 888 bp long and
      capable of encoding a polypeptide of 32 kDa. The deduced amino acid sequence of
      tfdR indicates that it is a member of the LysR-type activators. Investigation of
      the regulation of the catabolic gene clusters through the construction of a pJP4
      defined deletion mutant, pYG1010, which lacks a 4.2 kilobase Xbal fragment
      containing the inverted repeat region carrying the tfdR and tfdS regulatory
      genes, showed that Pseudomonas cepacia strains containing pYG1010 became 2,4-D
      negative, but 3-Cba positive. In vivo recombinants of pYG1010 and a cloned tfdS
      gene rescued the 2,4-D phenotype, indicating that TfdS is a positive regulator of
      tfdA expression, but not for tfdCDEF expression.

PMID- 7565095
TI  - A second ABC transporter is involved in oleandomycin resistance and its secretion
      by Streptomyces antibioticus.
AB  - A 3.2 kb Sstl-Sphl DNA fragment of Streptomyces antibioticus, an oleandomycin
      producer, conferring resistance to oleandomycin was sequenced and found to
      contain an open reading frame of 1710 bp (oleB). Its deduced gene product (OleB)
      showed a high degree of similarity with other proteins belonging to the ABC
      transporter superfamily including the gene product of another oleandomycin
      resistance gene (OleC). The OleB protein contains two ATP-binding domains, each
      of approximately 200 amino acids in length, and no hydrophobic transmembrane
      regions. Functional analysis of the oleB gene was carried out by deleting
      specific regions of the gene and assaying for oleandomycin resistance. These
      experiments showed that either the first or the second half of the gene
      containing only one ATP-binding domain was sufficient to confer resistance to
      oleandomycin. The gene oleB was expressed in Escherichia coli fused to a maltose
      binding protein (MBP) using the pMal-c2 vector. The MBP-OleB hybrid protein was
      purified by affinity chromatography on an amylose resin and polyclonal antibodies
      were raised against the fusion protein. These were used to monitor the
      biosynthesis and physical location of OleB during growth. By Western analysis,
      the OleB protein was detected both in the soluble and in the membrane fraction
      and its synthesis paralleled oleandomycin biosynthesis. It was also shown that a
      Streptomyces albus strain, containing both a glycosyltransferase (OleD) able to
      inactivate oleandomycin and the OleB protein, was capable of glycosylating
      oleandomycin and secreting the inactive glycosylated molecule. It is proposed
      that OleB constitutes the secretion system by which oleandomycin or its inactive
      glycosylated form could be secreted by S. antibioticus.

PMID- 7565096
TI  - The tagGH operon of Bacillus subtilis 168 encodes a two-component ABC transporter
      involved in the metabolism of two wall teichoic acids.
AB  - We report the nucleotide sequence and the characterization of the Bacillus
      subtilis tagGH operon. The latter is controlled by a sigma A-dependent promoter
      and situated in the 308 degrees chromosomal region which contains genes involved
      in teichoic acid biosynthesis. TagG is a hydrophobic 32.2 kDa protein which
      resembles integral membrane proteins belonging to polymer-export systems of Gram
      negative bacteria. Gene tagH encodes a 59.9 kDa protein whose N-moiety contains
      the ATP-binding motif and shares extensive homology with a number of ATP-binding
      proteins, particularly with those associated with the transport of capsular
      polysaccharides and O-antigens. That the tagGH operon is essential for cell
      growth was established by the failure to inactivate tagG and the 5'-moiety of
      tagH by insertional mutagenesis. During limited tagGH expression, cells exhibited
      a cocoid morphology while their walls contained reduced amounts of phosphate as
      well as galactosamine. These observations, revealing impaired metabolism of both
      wall teichoic acids of B. subtilis 168, i.e. poly(glycerol phosphate), and
      poly(glucose galactosamine phosphate), combined with sequence homologies, suggest
      that TagG and TagH are involved in the translocation through the cytoplasmic
      membrane of the latter teichoic acids or their precursors.

PMID- 7565097
TI  - Effects of upstream deletions on light- and oxygen-regulated bacterio-opsin gene
      expression in Halobacterium halobium.
AB  - The bacterio-opsin gene (bop) of Halobacterium halobium is located within a
      cluster with three other genes. Growth conditions of high light intensity and low
      oxygen tension induce bop gene cluster expression. To identify putative
      regulatory factor binding sites upstream of the bop gene, we have compared
      sequences upstream of the bop gene with the corresponding sequences from two
      other genes in the bop gene cluster. Conserved sequence motifs were observed
      which may mediate the effect of high light intensity and/or low oxygen tension on
      bop gene expression. Based on these motifs, a set of mutants was constructed
      which contained deletions upstream of the bop gene. These constructs were tested
      in a host strain where bop gene expression is independent of oxygen regulation
      and in another strain where it is regulated by oxygen and light. The minimal
      upstream sequence required for both light- and oxygen-regulated bop gene
      expression was determined to be 54 bp.

PMID- 7565099
TI  - Collapse and repair of replication forks in Escherichia coli.
AB  - Single-strand interruptions in a template DNA are likely to cause collapse of
      replication forks. We propose a model for the repair of collapsed replication
      forks in Escherichia coli by the RecBCD recombinational pathway. The model gives
      reasons for the preferential orientation of Chi sites in the E. coli chromosome
      and accounts for the hyper-rec phenotype of the strains with increased numbers of
      single-strand interruptions in their DNA. On the basis of the model we offer
      schemes for various repeat-mediated recombinational events and discuss a
      mechanism for quasi-conservative DNA replication explaining the recombinational
      repair-associated mutagenesis.

PMID- 7565098
TI  - Saturation of penicillin-binding protein 1 by beta-lactam antibiotics in growing
      cells of Bacillus licheniformis.
AB  - With the help of a new highly sensitive method allowing the quantification of
      free penicillin-binding proteins (PBPs) and of an integrated mathematical model,
      the progressive saturation of PBP1 by various beta-lactam antibiotics in growing
      cells of Bacillus licheniformis was studied. Although the results confirmed PBP1
      as a major lethal target for these compounds, they also underlined several
      weaknesses in our present understanding of this phenomenon. In growing cells, but
      not in resting cells, the penicillin target(s) appeared to be somewhat protected
      from the action of the inactivators. In vitro experiments indicated that amino
      acids, peptides and depsipeptides mimicking the peptide moiety of the nascent
      peptidoglycan significantly interfered with the acylation of PBP1 by the
      antibiotics. In addition, the level of PBP1 saturation at antibiotic
      concentrations corresponding to the minimum inhibitory concentrations was not
      constant, suggesting that additional, presently undiscovered, factors might be
      necessary to account for the experimental observations.

PMID- 7565100
TI  - Beta-lactamases and bacterial resistance to antibiotics.
AB  - The efficiency of beta-lactam antibiotics, which are among our most useful
      chemotherapeutic weapons, is continuously challenged by the emergence of
      resistant bacterial strains. This is most often due to the production of beta
      lactamases by the resistant cells. These enzymes inactivate the antibiotics by
      hydrolysing the beta-lactam amide bond. The elucidation of the structures of some
      beta-lactamases by X-ray crystallography has provided precious insights into
      their catalytic mechanisms and revealed unsuspected similarities with the DD
      transpeptidases, the bacterial enzymes which constitute the lethal targets of
      beta-lactams. Despite numerous kinetic, structural and site-directed mutagenesis
      studies, we have not completely succeeded in explaining the diversity of the
      specificity profiles of beta-lactamases and their surprising catalytic power. The
      solutions to these problems represent the cornerstones on which better
      antibiotics can be designed, hopefully on a rational basis.

PMID- 7565101
TI  - The role of anti-sigma factors in gene regulation.
AB  - Despite the isolation of an anti-sigma factor over 20 years ago, it is only
      recently that the concept of an anti-sigma factor emerged as a general mechanism
      of transcriptional regulation in prokaryotic systems. Anti-sigma factors bind to
      sigma factors and inhibit their transcriptional activity. Studies on the
      mechanism of action of anti-sigma factors has shed new light on the regulation of
      gene expression in bacteria, as the anti-sigma factors add another layer to
      transcriptional control via negative regulation. Their cellular roles are as
      diverse as FIgM of Salmonella typhimurium, which can be exported to sense the
      structural state of the flagellar organelle, to SpoIIAB of Bacillus subtilis
      participating in the switch from one cell type to another during the process of
      sporulation. Additionally, the bacteriophage T4 uses an anti-sigma factor to
      sabotage the Escherichia coli E.sigma 70 RNA polymerase in order to direct
      exclusive transcription of its own genes. Cross-linking, co-immunoprecipitations,
      and co-purification indicate that the anti-sigma factors directly interact with
      their corresponding sigma factor to negatively regulate transcription. In B.
      subtilis, anti anti-sigma factors regulate anti-sigma factors by preventing an
      anti-sigma factor from interacting with its cognate sigma factors, thereby
      allowing transcription to occur.

PMID- 7565102
TI  - IHF- and RpoN-dependent regulation of hydrogenase expression in Bradyrhizobium
      japonicum.
AB  - Sequence analysis of the Bradyrhizobium japonicum hydrogenase promoter regulatory
      region indicated the presence of a -24/-12 type promoter, which is recognized by
      RpoN, and a potential integration host factor (IHF)-binding site. B. japonicum
      rpoN1-/rpoN2- double mutants were deficient in hydrogen-uptake activity. Using
      plasmid-borne hup-lacZ fusions, it was shown that the rpoN mutants were also
      deficient in nickel-dependent transcriptional regulation of hydrogenase. Gel
      shift assays of the hydrogenase promoter regulatory region showed that purified
      IHF from Escherichia coli binds to a 210 bp fragment. DNase footprint analysis
      revealed a protected region of 31 bp between bases -44 and -75 from the
      transcription start site. Western analysis with B. japonicum soluble extract and
      antibodies against E. coli IHF gave two bands equivalent to molecular masses of
      12 and 14 kDa approximately. When the IHF-binding area is mutated on a plasmid
      borne hup-lacZ fusion, nickel-dependent transcriptional regulation of hydrogenase
      is still observed, but the transcriptional rates are clearly less than in the
      parent hup-lacZ fusion plasmid. Like the results with nickel, regulation of
      hydrogenase by other transcriptional regulators (hydrogen and oxygen) still
      occurs, but at a diminished level in the IHF-binding-area-mutated construct.

PMID- 7565103
TI  - The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative
      stress responses of Saccharomyces cerevisiae.
AB  - The YAP1 and YAP2 genes encode yeast transcription factors of the c-jun family.
      We show that yeast mutants deleted for either the YAP1 or the YAP2 genes are
      hypersensitive to oxidants, particularly H2O2, and that these genes play a role
      in regulating the induction of the H2O2 adaptive stress response in Saccharomyces
      cerevisiae. They do not significantly affect the regulation of the superoxide
      adaptive stress response. The intrinsic resistance of stationary-phase and
      respiring yeast cells towards superoxide anions is unaffected by deletion of the
      YAP1 and YAP2 genes. However, resistance towards H2O2 under these conditions is
      significantly reduced. We show that expression of the yeast GSH1 gene (encoding
      gamma-glutamylcysteine synthetase) and the SSA1 gene (encoding an HSP70 isoform)
      are induced by oxidants. Unlike the SSA1 and thioredoxin (TRX2) genes, expression
      of the GSH1 gene is more strongly induced by superoxide anions than by H2O2. In
      the absence of added oxidants, transcription of the GSH1 gene is reduced in
      strains carrying the yap1 deletion. However, we show that Yap1 is not required
      for the superoxide anion-mediated induction of GSH1 gene expression. Furthermore,
      while the H2O2-mediated induction of SSA1 expression is shown to by YAP1
      dependent, the heat-shock-mediated induction of the SSA1 gene does not require
      YAP1. We also present evidence to show that the YAP2 gene does not regulate the
      expression of the TRX2, SSA1 or GSH1 genes.

PMID- 7565104
TI  - Organization of tcp, acf, and toxT genes within a ToxT-dependent operon.
AB  - The toxin coregulated pilus (TCP) is required for Vibrio cholerae to colonize the
      human intestine. The expression of the pilin gene, tcpA, is dependent upon ToxR
      and upon ToxT. The toxT gene was recently mapped within the TCP biogenesis gene
      cluster and shown to be capable of activating a tcpA::TnphoA fusion when cloned
      in Escherichia coli. In this study, we determined that ToxR/ToxT activation
      occurs at the level of tcpA transcription. ToxT expressed in E. coli could
      activate a tcp operon fusion, while ToxR, ToxR with ToxS, or a ToxR-PhoA fusion
      failed to activate the tcp operon fusion and we could not demonstrate binding of
      a ToxR extract to the tcpA promoter region in DNA mobility-shift assays. The
      start site for the regulated promoter was shown by primer extension to lie 75 bp
      upstream of the first codon of tcpA. An 800-base tcpA message was identified, by
      Northern analysis, that correlates by size to the distance between the
      transcriptional start and a hairpin-loop sequence between tcpA and tcpB. The more
      sensitive assay of RNase protection analysis demonstrated that a regulated
      transcript probably extends through the rest of the downstream tcp genes,
      including toxT and the adjacent accessory colonization factor (acf) genes. An in
      frame tcpA deletion, but not a polar tcpA::TnphoA fusion, could be complemented
      for pilus surface expression by providing tcpA in trans. This evidence suggests
      that the tcp genes, including toxT, are organized in an operon directly activated
      by ToxT in a ToxR-dependent manner. Most of the toxT expression under induced
      conditions requires transcription of the tcpA promoter. Further investigation of
      how tcp::TnphoA insertions that are polar on toxT expression retain regulation
      showed that a low basal level of toxT expression is present in toxR and
      tcp::TnphoA strains. Overall, these observations support the ToxR/ToxT cascade of
      regulation for tcp. Once induced, toxT expression becomes autoregulatory via the
      tcp promoter, linking tcp expression to that of additional colonization factors,
      exotoxin production, and genes of unknown function in cholera pathogenesis.

PMID- 7565105
TI  - Molecular cloning and functional expression of bacteriophage PK1E-encoded
      endoneuraminidase Endo NE.
AB  - Homopolymeric alpha-2,8-linked sialic acid (PSA) has been found as a capsular
      component of sepsis- and meningitis-causing bacterial pathogens, and on
      eukaryotic cells as a post-translational modification of the neural cell adhesion
      molecule (NCAM). The polysaccharide is specifically recognized and degraded by a
      phage-encoded enzyme, the endo-N-acetylneuraminidase E (Endo NE). Endo NE
      therefore has become a valuable tool in the study of bacterial pathogenesis and
      eukaryotic morphogenesis. In this report we describe the molecular cloning of
      Endo NE and the expression of a functionally active recombinant enzyme. The
      cloned DNA sequence (2436 bp) encodes a polypeptide of 811 amino acids, which at
      the 5' end contains a totally conserved neuraminidase motif. Expressed in
      Escherichia coli, the enzyme migrates as a single band of approximately 74 kDa in
      SDS-PAGE. A central domain of 669 amino acid residues is about 90% homologous to
      the recently cloned Endo NF. Both phage-induced lysis of bacteria and the
      catalysis of PSA degradation by the recombinant enzyme are efficiently inhibited
      by a polyclonal antiserum raised against the intact phage particle. The C
      terminal region seems to be essential to enzymatic functions, as truncation of 32
      amino acids outside the homology domain completely abolishes Endo NE activity.
      Our data also indicate that the 38 kDa protein, previously assumed to be a
      subunit of the Endo NE holoenzyme, is the product of a separate gene locus and is
      not necessary for in vitro depolymerase activity.

PMID- 7565107
TI  - The phoP locus influences processing and presentation of Salmonella typhimurium
      antigens by activated macrophages.
AB  - The destruction and processing of bacteria by activated macrophages facilitates
      the presentation of antigens to T cells and thereby promotes the induction of
      specific immunity. The PhoP-PhoQ regulatory system that controls the synthesis of
      many Salmonella proteins required for virulence and survival within macrophages
      is one mechanism that this particular intracellular pathogen has evolved to
      resist destruction. To address whether the phoP locus also influences antigen
      processing during the interaction of Salmonella typhimurium with macrophages, we
      tested the effect of phoP mutations on the processing and presentation of model
      antigens expressed by the bacteria. Activated macrophages processed phoP-
      bacteria with greater efficiency than wild-type bacteria, as measured by the
      response of antigen-specific T-hybridoma cells; Salmonella constitutively
      expressing PhoP were processed even less efficiently than wild-type Salmonella.
      After heat-inactivation, however, both wild-type and phoP- bacteria were
      efficiently processed. The altered processing and presentation efficiency was not
      due to differences in the level of antigen expressed by the bacteria or
      differences in the level of bacterial uptake by the macrophages. In addition,
      phoP-regulated gene expression was shown to influence processing of antigen
      phagocytosed independently of the bacteria. Thus, phoP-regulated gene products
      decrease the processing and presentation of S. typhimurium antigens,
      demonstrating a role for this virulence locus in the inhibition of the induction
      of specific immunity.

PMID- 7565106
TI  - Identification and characterization of pilG, a highly conserved pilus-assembly
      gene in pathogenic Neisseria.
AB  - Expression of type IV pili appears to be a requisite determinant of infectivity
      for the strict human pathogens Neisseria gonorrhoeae and Neisseria meningitidis.
      The assembly of these colonization factors is a complex process. This report
      describes a new pilus-assembly gene, pilG, that immediately precedes the
      gonococcal (Gc) pilD gene encoding the pre-pilin leader peptidase. The nucleotide
      sequence of this region revealed a single complete open reading frame whose
      derived polypeptide displayed significant identities to the pilus-assembly
      protein PilC of Pseudomonas aeruginosa and other polytopic integral cytoplasmic
      membrane constituents involved in protein export and competence. A unique
      polypeptide of M(r) 38 kDa corresponding to the gene product was identified. A
      highly related gene and flanking sequences were cloned from a group B
      polysaccharide-producing strain of N. meningitidis (Mc). The results indicate
      that the pilG genes and genetic organization at these loci in Gc and Mc are
      extremely conserved. Hybridization studies strongly suggest that pilG-related
      genes exist in commensal Neisseria species and other species known to express
      type IV pili. Defined genetic lesions were created by using insertional and
      transposon mutagenesis and moved into the Gc and Mc chromosomes by allelic
      replacement. Chromosomal pilG insertion mutants were devoid of pili and displayed
      dramatically reduced competence for transformation. These findings could not be
      ascribed to pilin-gene alterations or to polarity exerted on pilD expression. The
      results indicated that PilG exerts its own independent role in neisserial pilus
      biogenesis.

PMID- 7565108
TI  - Plasmid pT181 replication is decreased at high levels of RepC per plasmid copy.
AB  - The replication of staphylococcal plasmid pT181 is indirectly controlled at the
      level of the synthesis of its replication initiator, RepC. As a result, high
      levels of RepC synthesis per plasmid copy were expected to lead to autocatalytic
      plasmid replication, which secondarily would affect host physiology.
      Surprisingly, RepC overexpression was found to lead to a rapid decrease in pT181
      copy number and replication rate. These effects depended on the ratio of RepC to
      the pT181 replication origin rather than on the absolute amount of RepC in the
      cell. In a wild-type host, the increase in RepC/plasmid copy also inhibited
      chromosome replication and cell division. The changes in host physiology did not
      play any role in the decrease in pT181 replication caused by RepC overexpression
      since pT181 replication responded in the same way in a host mutant insensitive to
      the effects of RepC induction. These results suggest that pT181, the prototype of
      an entire class of plasmids from Gram-positive bacteria, responds to
      overexpression of its replication initiator by a decrease in plasmid replication.

PMID- 7565109
TI  - Identification of a gene, pilV, required for type 4 fimbrial biogenesis in
      Pseudomonas aeruginosa, whose product possesses a pre-pilin-like leader sequence.
AB  - Type 4 fimbriae are important colonization factors in Pseudomonas aeruginosa and
      other pathogens that mediate attachment to epithelial cells of the host. They are
      also responsible for a form of translocation termed 'twitching motility' and are
      implicated in the susceptibility to fimbrial-specific bacteriophage. Analysis of
      a transposon mutant which lacks functional fimbriae has identified a new gene
      which is required for fimbrial biogenesis. This gene, termed pilV, is located on
      chromosomal SpeI fragment E, 2 kb downstream of the previously characterized
      pilSR genes involved in transcriptional activation of the fimbrial subunit gene.
      The pilV gene encodes a 20 kDa membrane-located protein with considerable amino
      terminal homology to the type 4 consensus pre-pilin leader sequence, suggesting
      that it is processed by a leader peptidase. Site-directed mutagenesis has shown
      that PilV requires such cleavage to be functional. PilV also exhibits close
      similarity to a group of proteins involved in extracellular protein secretion
      from a number of Gram-negative bacteria, suggesting that the biogenesis of type 4
      fimbriae may have a similar basis.

PMID- 7565110
TI  - Characterization of a five-gene cluster required for the biogenesis of type 4
      fimbriae in Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa produces type 4 fimbriae which
      promote adhesion to epithelial cells and are associated with a form of surface
      translocation called twitching motility. Transposon mutagenesis was used to
      identify loci required for fimbrial assembly or function by screening for mutants
      that lack the spreading colony morphology characteristic of twitching motility.
      Six mutants were isolated that contain transposon insertions upstream of the
      previously characterized gene pilQ. This region contains four genes: pilM-P,
      which encode proteins with predicted sizes of 37.9, 22.2, 22.8 and 19.0 kDa,
      respectively. pilM-P appear to form an operon and to be expressed from a promoter
      in the intergenic region between pilM and the divergently transcribed upstream
      gene ponA. PilM-P were found to be required for fimbrial biogenesis by
      complementation studies using twitching motility and sensitivity to fimbrial
      specific phage as indicators of the presence of functional fimbriae. This was
      confirmed by electron microscopy. PilO and PilP did not have homologues in the
      sequence databases, but the predicted PilN amino acid sequence displayed
      similarity to XpsL from Xanthamonas campestris, a protein required for protein
      secretion. PilP contained a hydrophobic leader sequence characteristic of
      lipoproteins, while PilN and PilO have long internal hydrophobic domains which
      may serve to localize them to the cytoplasmic membrane. PilM has shared sequence
      motifs with the cell division protein FtsA from Bacillus subtilis and Escherichia
      coli, as well as the rod-shape-determining protein MreB from E. coli. These
      motifs are also conserved in eukaryotic actin, in which they are involved in
      forming an ATPase domain. Deletion mutants of pilM and pilQ displayed a dominant
      negative phenotype when transformed into wild-type cells, suggesting that these
      genes encode proteins involved in multimeric structures.

PMID- 7565111
TI  - Molecular population genetic analysis of the streptokinase gene of Streptococcus
      pyogenes: mosaic alleles generated by recombination.
AB  - To understand the mechanisms governing molecular evolution of the streptokinase
      gene (skn), a 384 bp DNA fragment encoding two variable regions of the molecule
      was characterized in 47 isolates of Streptococcus pyogenes. The results reveal
      that alleles of the streptokinase gene have a mosaic structure, and provide
      strong evidence for intragenic recombination. Moreover, organisms that are well
      differentiated in overall chromosomal character have identical skn alleles, which
      suggests that horizontal gene transfer and recombination have participated in the
      evolution of this locus. No simple relationship between skn allele and serum
      opacity factor production or specific disease was identified. The predicted amino
      acid sequences of highly divergent skn alleles are strikingly similar in
      hydrophilicity and hydrophobicity profiles, distribution of amphipathic and
      flexible regions, surface probability plots, and antigenic indices, indicating
      that despite extensive nucleotide polymorphism in the two skn variable regions,
      selective pressure has constrained overall structural divergence. These results
      add to an important emerging theme that intragenic recombination plays a critical
      role in diversifying genes coding for streptococcal virulence factors.

PMID- 7565113
TI  - Molecular genetics of the chloramphenicol-resistance transposon Tn4451 from
      Clostridium perfringens: the TnpX site-specific recombinase excises a circular
      transposon molecule.
AB  - The chloramphenicol-resistance transposon Tn4451 undergoes precise conjugative
      deletion from its parent plasmid plP401 in Clostridium perfringens and precise
      spontaneous excision from multicopy plasmids in Escherichia coli. The complete
      nucleotide sequence of the 6338 bp transposon was determined and it was found to
      encode six genes. Genetic analysis demonstrated that the largest Tn4451-encoded
      gene, tnpX, was required for the spontaneous excision of the transposon in both
      E. coli and C. perfringens, since a Tn4451 derivative that lacked a functional
      tnpX gene was completely stable in both organisms. Because the ability of this
      derivative to excise was restored by providing the tnpX gene on a compatible
      plasmid, it was concluded that this gene encoded a trans-acting site-specific
      recombinase. Allelic exchange was used to introduce the tnpX delta 1 allele onto
      plP401 and it was shown that TnpX was also required for the conjugative excision
      of Tn4451 in C. perfringens. It was also shown by hybridization and polymerase
      chain reaction (PCR) studies that TnpX-mediated transposon excision resulted in
      the formation of a circular form of the transposon. The TnpX recombinase was
      unique because it potentially contained the motifs of two independent site
      specific recombinase families, namely the resolvase/invertase and integrase
      families. Sequence analysis indicated that the resolvase/invertase domain of TnpX
      was likely to be involved in the excision process by catalysing the formation of
      a 2 bp staggered nick on either side of the GA dinucleotide located at the ends
      of the transposon and at the junction of the circular form. The other Tn4451
      encoded genes include tnpZ, which appears to encode a second potential site
      specific recombinase. This protein has similarity to plasmid-encoded Mob/Pre
      proteins, which are involved in plasmid mobilization and multimer formation.
      Located upstream of the tnpZ gene was a region with similarity to the site of
      interaction of these mobilization proteins.

PMID- 7565112
TI  - Transcriptional regulation of the proton translocating NADH dehydrogenase genes
      (nuoA-N) of Escherichia coli by electron acceptors, electron donors and gene
      regulators.
AB  - The promoter region and transcriptional regulation of the nuoA-N gene locus
      encoding the proton-translocating NADH:quinone oxidoreductase was analysed. A 560
      bp intergenic region upstream of the nuo locus was followed by a gene (designated
      lrhA for LysR homologue A) coding for a gene regulator similar to those of the
      LysR family. Disruption of lrhA did not affect growth (respiratory or non
      respiratory) or expression of nuo significantly. Transcriptional regulation of
      nuo by electron acceptors, electron donors and the transcriptional regulators
      ArcA, FNR, NarL and NarP, and by IHF (integration host factor) was studied with
      protein and operon fusions containing the promoter region up to base pair -277
      ('nuo277') or up to base pair -89 ('nuo899'). The expression of the nuo277-lacZ
      fusions was subject to ArcA-mediated anaerobic repression and NarL(+ nitrate)
      mediated anaerobic activation. FNR and IHF acted as weak repressors under
      anaerobic conditions. Expression of nuo899-lacZ was stimulated during anaerobic
      fumarate respiration and aerobically by C4 dicarboxylates. Therefore, expression
      of nuo is regulated by O2 and nitrate via ArcA, NarL, FNR and IHF at sites within
      the -277 region, and by other factors including C4 dicarboxylates at a site
      between -277 and -899. A physiological role for the transcriptional stimulation
      by O2 and nitrate is suggested.

PMID- 7565114
TI  - Characterization of the osmotically inducible gene osmE of Escherichia coli K-12.
AB  - osmE, an osmotically inducible gene of Escherichia coli, was physically mapped on
      the bacterial chromosome, cloned and sequenced. osmE appeared to encode a 12,021
      Da protein of unknown function, with a lipoprotein-type signal sequence at the
      amino-terminus. The osmE reading frame was confirmed by sequencing the junction
      of an osmE-phoA gene fusion. osmE was demonstrated to be transcribed as a single
      cistron. A phi [osmEp-lac] operon fusion was constructed, and analysis of its
      expression demonstrated that osmE osmotic regulation probably occurs at the
      transcriptional level. The osmE promoter was identified by both S1 nuclease and
      primer extension mapping of the 5' end of the osmE mRNA, by deletion analysis and
      by identification of a point mutation reducing its activity. Sequence information
      sufficient for expression and osmotic regulation is present on a DNA fragment
      extending from positions -37 to +52 with respect to the osmE transcription start.
      Uninduced expression of the osmE-lac fusion was increased in the presence of
      mutations in the hns and himA genes. The osmE promoter overlaps a promoter for a
      gene transcribed in the opposite direction, efg. Transcription from the efg
      promoter is only weakly affected by osmotic pressure and is independent of the
      presence of an intact OsmE protein.

PMID- 7565116
TI  - Characterization of the pilF-pilD pilus-assembly locus of Neisseria gonorrhoeae.
AB  - Expression of Type IV pili by the bacterial pathogen Neisseria gonorrhoeae
      appears to be essential for colonization of the human host. Several N.
      gonorrhoeae gene products have been recently identified which bear homology to
      proteins involved in pilus assembly and protein export in other bacterial
      systems. We report here the isolation and characterization of transposon
      insertion mutants in N. gonorrhoeae whose phenotypes indicate that the N.
      gonorrhoeae pilF and pilD gene products are required for gonoccocal pilus
      biogenesis. Mutants lacking the pilD gene product, a pre-pilin peptidase, were
      unable to process the pre-pilin subunit into pilin and thus were non-piliated.
      pilF mutants processed pilin but did not assemble the mature subunit. Both
      classes of mutants released S-pilin, a soluble, truncated form of the pilin
      subunit previously correlated with defects in pilus assembly. In addition,
      mutants containing transposon insertions in pilD or in a downstream gene, orfX,
      exhibited a severely restricted growth phenotype. Deletion analysis of pilD
      indicated that the poor growth phenotype observed for the pilD transposon mutants
      was a result of polar effects of the insertions on orfX expression. orfX encodes
      a predicted polypeptide of 23 kDa which contains a consensus nucleotide-binding
      domain and has apparent homologues in Pseudomonas aeruginosa, Pseudomonas putida,
      Thermus thermophilus, and the eukaryote Caenorhabditis elegans. Although
      expression of orfX and pilD appears to be transcriptionally coupled, mutants
      containing transposon insertions in orfX expressed pili. Unlike either pilF or
      pilD mutants, orfX mutants were also competent for DNA transformation.

PMID- 7565115
TI  - Molecular cloning and characterization of the rfc gene of Pseudomonas aeruginosa
      (serotype O5).
AB  - Previous work from our laboratory has shown that cosmid clone pFV100, containing
      a 26 kb insert, is able to restore O-antigen synthesis in serotype O5 rough
      mutants of Pseudomonas aeruginosa. Mobilization of pFV100 into two P. aeruginosa
      semi-rough (SR) mutants, AK14O1 and rd7513, resulted in O-antigen expression,
      indicating that pFV100 may contain an O-polymerase (rfc) gene. pFV.TK6, a
      subclone of pFV100 that contains a 5.6 kb chromosomal insert, was able to
      complement O-antigen expression in these SR mutants. Mutagenesis of pFV.TK6 using
      Tn1000 exposed a 1.5 kb region that was essential for complementing O-antigen
      expression in AK14O1. A 2.0 kb XhoI-HindIII fragment, containing this region, was
      cloned into vector pUCP26 and the resulting plasmid called pFV.TK8. In Southern
      analysis of the 20 P. aeruginosa serotypes using a probe generated from the 1.5
      kb XhoI fragment of pFV.TK8, the rfc probe hybridized to a common fragment of the
      cross-reactive O2-O5-O16-O18-O20 serogroup, suggesting that these serotypes may
      share a common O-polymerase gene. In functional studies of the rfc gene, the PAO1
      (serotype O5) chromosomal rfc was mutated using a gene-replacement strategy.
      These knockout mutants expressed the SR lipopolysaccharide (LPS) phenotype, which
      indicated that they were no longer producing a functional O-polymerase enzyme.
      Nucleotide sequence analysis of the insert DNA of pFV.TK8 revealed one open
      reading frame (ORF), designated ORF48.9, which could code for a 48.9 kDa protein.
      In comparisons of the P. aeruginosa rfc nucleotide and amino acid sequences with
      DNA and protein databases, no significant homology was found. However, the
      deduced structure of the P. aeruginosa Rfc protein indicated that it is very
      hydrophobic and contains 11 putative membrane-spanning domains. Therefore, the
      predicted structure is similar to that of other reported Rfc proteins.
      Furthermore, comparison of the amino acid composition and codon usage of the P.
      aeruginosa Rfc with other Rfc proteins revealed significant similarity between
      them.

PMID- 7565117
TI  - Resistance to mecillinam produced by the co-operative action of mutations
      affecting lipopolysaccharide, spoT, and cya or crp genes of Salmonella
      typhimurium.
AB  - Lipopolysaccharide (LPS), spoT, and cya or crp mutations individually do not
      affect the minimum inhibitory concentration of mecillinam on Salmonella
      typhimurium. However, when mutations of two of these types were combined in the
      same strain, high-level resistance appeared, and increased even further when all
      three types of mutations were present. Most mutations affecting LPS (rfa, rfb,
      rfc) showed this behaviour, although to different degrees. The highest resistance
      to mecillinam was caused by galE and rfc mutations whereas almost no effect was
      noticed with rfaB or rfaK mutations. This phenomenon appears to be specific for
      mecillinam since none of several other antibiotics elicited it. Reduction of
      guanosine tetraphosphate (ppGpp) levels by introduction of a relA mutation did
      not significantly affect the MIC of mecillinam on strains carrying different
      combinations of spoT, galE, and cya or crp mutations. All the strains produced
      spherical cells in medium with a low concentration (0.05 microgram ml-1) of the
      antibiotic. These results suggest that the antibacterial action of mecillinam on
      S. typhimurium is somehow dependent on the interaction of LPS, cyclic AMP/cyclic
      AMP receptor protein (cAMP/CRP), and SpoT. The reported resistance to mecillinam
      of cya and crp mutants of Escherichia coli K-12 is probably due to the natural
      LPS defectiveness of this strain.

PMID- 7565118
TI  - Purification of ArcA and analysis of its specific interaction with the pfl
      promoter-regulatory region.
AB  - ArcA is one of several transcription factors required for optimal anaerobic
      induction of the pyruvate formatelyase (pfl) operon. To aid the study at the
      molecular level of the interaction of ArcA with the pfl promoter-regulatory
      region we developed a procedure for the isolation of ArcA. The purification of
      ArcA involved chromatography in heparin agarose, hydroxylapatite and Mono-Q
      matrices and delivered a protein that was > 95% pure. Gel retardation assays
      demonstrated that ArcA bound specifically to the pfl regulatory region. Three
      distinct ArcA-DNA complexes could be resolved depending on the ArcA concentration
      used. This finding suggested that either multiple ArcA-binding sites are present
      in the regulatory region or that ArcA can oligomerize at one or more sites. The
      DNA-binding activity of ArcA could be increased as estimated 10-fold by prior
      incubation of the protein with carbamoyl phosphate, suggesting that
      phosphorylation activates DNA binding or oligomerisation. DNase I footprint
      analyses identified four sites that were protected by ArcA from cleavage. Two of
      these sites spanned the transcription start site and -10 regions of promoters 6
      and 7, while a third site partially overlapped the characterized binding site of
      integration host factor (IHF). ArcA exhibited the highest affinity for a stretch
      of DNA located between the IHF site and the transcription start site of promoter
      7. These results are congruent with the hypothesis that a higher-order
      nucleoprotein complex comprising several proteins, including ArcA, is required to
      activate transcription from the multiple promoters of the pfl operon.

PMID- 7565119
TI  - The consequences of malaria infection in pregnant women and their infants.
AB  - Preliminary results are presented from this study which indicate that 84.8% of
      pregnant women present at first antenatal visit with anemia (Hb 11g/dl) an 8.7%
      of their infants (n = 230) have a hemoglobin at birth below 14g/dl. There is an
      association between pregnancy anemia and malaria. A case control study in
      pregnant women and an infant cohort study to 18 months of age, are employed to
      study the cause and effects of anemia and malaria on women and their infants
      health.

PMID- 7565120
TI  - Chimpanzees and supporting models in the study of malaria pre-erythrocytic
      stages.
AB  - Chimpanzees are being used in the study of immune response to Plasmodium
      falciparum malaria pre-erythrocytic stages (MPES). Responses induced by
      immunisation with recombinant/synthetic antigens and by irradiated sporozoites
      are being evaluated in a model system that is phylogenetically close to humans
      and that is amenable to limited manipulation not possible in humans. The value of
      chimpanzees for the in-depth study of immunological mechanisms at work in MPES
      induced protection are discussed. A total number of 7 chimpanzees have been used
      to evaluate the immune response to recombinant antigens, and 5 have been
      challenged with large numbers of sporozoites, followed by surgical liver-wedge
      resection, in order to generate infected liver tissue for histological and
      immunological studies. As a complementary model, SCID mice carrying live,
      transplanted human and primate hepatocytes have been inoculated with sporozoites
      and infection of transplanted cells has been monitored by histological and
      immunological methods. In ongoing experiments chimpanzees are being immunised
      with MPES-derived lipopeptides that have been shown to overcome MHC restriction
      in mice, and with irradiated sporozoites.

PMID- 7565121
TI  - Development of sporogonic cycle of Plasmodium vivax in experimentally infected
      Anopheles albimanus mosquitoes.
AB  - The sporogonic cycle of Plasmodium vivax was established and maintained under
      laboratory conditions in two different strains of Anopheles albimanus mosquitoes
      using as a parasite source blood from human patients or from Aotus monkeys
      infected with the VCC-2 P.vivax colombian isolate. Both the Tecojate strain
      isolate from Guatemala and the Cartagena strain from the colombian Pacific coast
      were susceptible to infections with P.vivax. A higher percentage of Cartagena
      mosquitoes was infected per trial, however the Tecojate strain developed higher
      sporozoite loads. Intravenous inoculation of Aotus monkeys with sporozoites
      obtained from both anopheline strains resulted in successful blood infections.
      Animals infected with sporozoites from the Tecojate strain presented a patent
      period of 21-32 days whereas parasitemia appeared between days 19-53 in monkeys
      infected with sporozites from Cartagena strain.

PMID- 7565122
TI  - Transmission blocking immunity as observed in a feeder system and serological
      reactivity to Pfs 48/45 and Pfs230 in field sera.
AB  - Monoclonal antibodies (mAbs) and human sera from gametocyte carriers were applied
      in the bio-assay to test for their transmission-blocking capacity. Competition
      ELISA's have been developed for the detection of natural transmission blocking
      antibodies. Approximately 55% of the sera blocking in the bio-assay gave positive
      results in these competition ELISA's.

PMID- 7565123
TI  - Serum factors inhibitory for in vitro development of Plasmodium falciparum blood
      stage parasites.
AB  - Sera from 29 individuals residing in a malaria-endemic region of Colombia were
      evaluated by an inhibition assay for their capacity to retard the growth of
      Plasmodium falciparum in vitro. The inhibitory activity was found to be
      independent of antibody activity. Furthermore, the degree of inhibition of
      parasite development was variable, depending on the parasite isolate used for the
      assay and the season of malaria transmission. We selected sera with high
      inhibitory activity and carried out partial analytical characterization by anion
      exchange fast protein liquid chromatography (FPLC) to identify the chemical
      nature of the inhibitory factor(s). The results suggested that the in vitro
      inhibitory activity might result from the additive effect of different molecules.
      It appears that these molecules could be non-specifically induced by stimulation
      of the immune system, they seem to play a role in the immunity to malaria.

PMID- 7565125
TI  - Interactions between parasites and insects vectors.
AB  - This review stresses the importance of studies that will provide a basic
      understanding of the pathology of parasite-infected vector insects. This
      knowledge should be a vital component of the very focussed initiatives currently
      being funded in the areas of vector control. Vector fecundity reduction is
      discussed as an example of such pathology. Underlying mechanisms are being
      investigated in a model system, Hymenolepis diminuta-infected Tenebrio molitor
      and in Onchocerca-infected blackflies and Plasmodium-infected Anopheles
      stephensi. In all cases, host vitellogenesis is disrupted by the parasite and, in
      the tapeworm/beetle model, interaction between the parasite and the endocrine
      control of the insect's reproductive physiology has been demonstrated.

PMID- 7565124
TI  - Early sporogonic development in local vectors of Plasmodium falciparum in rural
      Cameroon.
AB  - In ongoing studies on experimental transmission of Plasmodium falciparum in the
      city of Yaounde gametocyte carriers are daily being identified among dispensary
      patients with malaria-like complaints. This species comprises 93% of all
      parasitemias and because of the selection criteria most patients have it as a
      recent infection. 17% of all P. falciparum-positives carry detectable gametocytes
      with little difference between youngsters and adults. Blood of adult carriers is
      taken and infection of Anopheles gambiae mosquitoes is attempted by membrane
      feeding; the establishment of infection is judged by the presence of oocysts.

PMID- 7565127
TI  - Subtelomeric structure of Plasmodium falciparum chromosomes.
AB  - Previous studies of subtelomeric regions in Plasmodium berghei led to the
      identification of subtelomeric repeats (2.3kb long) present in a variable number
      at many chromosomal ends. Both loss and increase in 2.3kb-repeat copy number are
      involved in chromosome-size polymorphisms. Subtelomeric losses leading to
      chromosome-size polymorphisms have been described by several authors in
      P.falciparum where the structure of subtelomeric regions is not known in detail.
      We therefore undertook their characterisation, by means of chromosome walking and
      jumping techniques, starting from the telomere-flanking sequence present in
      pPftel.1, the P.falciparum telomeric clone described by Vernick and McCutchan
      (1988). The results indicate that at least 20 (out of 28) chromosomal ends in
      P.falciparum 3D7 chromosomes share a subtelomeric region, about 40kb long,
      covering (but not limited to) the Rep20 region. Non repetitive, AT-rich portions
      flanking the Rep20 region on both sides are also conserved at most chromosomal
      ends.

PMID- 7565126
TI  - A double comparative study of the acceptability of untreated bed nets versus
      permethrin, lambda-cyhalothrin and deltamethrin impregnated bed nets.

PMID- 7565128
TI  - Isolation of a distally located gene possibly correlated with gametocyte
      production ability.
AB  - Previous studies were focussed on the attempt to correlate observable variations
      in the size of Plasmodium berghei chromosomes with the loss of ability to produce
      viable gametocytes. A temporal coincidence between the appearance of a
      subtelomeric deletion on P. berghei chromosome 5 and the loss of the ability to
      produce viable gametocytes was observed in a clone (HPE) directly derived from
      the high gametocyte-producer clone 8417 during mechanical passages. Interestingly
      enough, three P. berghei sexual-specific genes have already been mapped on
      internal fragments of this chromosome. A novel gene, clone 150, isolated from a
      genomic library of clone 8417 using a probe enriched for sexual-specific
      transcripts, maps on chromosome 5 within 100kb from the telomere. Subtelomeric
      deletions of chromosome 5 affecting two non-producer clones involve part of the
      transcribed region of this gene.

PMID- 7565129
TI  - Attempted isolation of the gene encoding the 21 Kd Plasmodium berghei ookinete
      transmission blocking antigen from Plasmodium yoelli and Plasmodium vivax.
AB  - The 21kD ookinete antigen of Plasmodium berghei (Pbs 21) has been shown to elicit
      an effective and long lasting transmission blocking immune response in mice.
      Having cloned and sequenced this antigen (Paton et al. 1993) the sequence was
      compared to the genes of the same family previously identified in P. falciparum,
      P. gallinaceum (Kaslow et al. 1989) and P. reichenowi (Lal et al. 1990). Four
      conserved areas were identified in this comparison, to which degenerate
      oligonucleotides were designed. PCR amplification and screening of genomic
      libraries was then carried out using these oligonucleotides. The P. yoelii gene
      was successfully cloned and a number of novel P. vivax genes identified but the
      P. vivax homologue of Pbs21 remains elusive.

PMID- 7565130
TI  - Chromosomes and sexual development of rodent malaria parasites.

PMID- 7565131
TI  - Plasmodium falciparum proteinases: cloning of the putative gene coding for the
      merozoite proteinase for erythrocyte invasion (MPEI) and determination of
      hydrolysis sites of spectrin by Pf37 proteinase.
AB  - Numerous proteinase activities have been shown to be essential for the survival
      of Plasmodium falciparum. One approach to antimalarial chemotherapy, would be to
      block specifically one or several of these activities, by using compounds
      structurally analogous to the substrates of these proteinases. Such a strategy
      requires a detailed knowledge of the active site of the proteinase, in order to
      identify the best substrate for the proteinase. Aiming at developing such a
      strategy, two proteinases previously identified in our laboratory, were chosen
      for further characterization of their molecular structure and properties: the
      merozoite proteinase for erythrocytic invasion (MPEI), involved in the
      erythrocyte invasion by the merozoites, and the Pf37 proteinase, which hydrolyses
      human spectrin in vitro.

PMID- 7565132
TI  - Immune mechanisms underlying the premunition against Plasmodium falciparum
      malaria.
AB  - The most unique characteristic of a parasite when it is in its normal host is the
      ability to make itself tolerated, which clearly indicates that it has
      sophisticated means to ensure the neutrality of its host. This is true also in
      the case of Plasmodium falciparum, since after numerous malaria attacks an
      equilibrium is reached with a chronic stage of infection, characterized by a
      relatively low parasitemia, and low or no disease (Sergent & Parrot 1935). We
      shall briefly review the main characteristics of this state of "premunition", and
      present data suggesting that the underlying mechanisms of defense rely on the
      cooperation between cell and antibodies, leading to an antibody dependent
      cellular inhibition of the intra-erythrocytic growth of the parasite.

PMID- 7565133
TI  - Naturally acquired antibodies against the major merozoite surface coat protein
      (MSP-1) of Plasmodium falciparum acquired by residents in an endemic area of
      Colombia.
AB  - A preliminary baseline epidemiological malaria survey was conducted in the
      village of Punta Soldado, Colombia. Parasite prevalence and density as well as
      serological data were obtained from 151 asymptomatic children and adults. Fifty
      individuals were infected with Plasmodium falciparum. The mean parasite density
      was 184 parasites/mm3. Greater than 90% of the sample population were P.
      falciparum antibody positive as detected by the indirect immunofluorescent
      antibody test (IFAT). The enzyme-linked immunosorbent assay (ELISA) was used to
      detect antibodies against the major merozoite surface protein (MSP-1) of P.
      falciparum. In this population, anti-MSP-1 antibody concentration is acquired in
      an age dependent manner with equal immunogenicity to both the N- and C-terminal
      regions of the molecule. Infection at the time of sampling was associated with a
      higher anti-MSP-1 antibody concentration than that found in non-infected
      individuals. Further studies are planned to assess the role of immune and non
      immune factors in limiting the number of cases of severe malaria seen in this
      population.

PMID- 7565134
TI  - Patterns of acquired anti-malarial immunity in Sri Lanka.

PMID- 7565135
TI  - Aspects of immunity for the AMA-1 family of molecules in humans and non-human
      primates malarias.
AB  - The apical membrane antigen (AMA-1) family of malaria merozoite proteins is
      characterised by a high degree of inter-species conservation. Evidence that the
      protein (PK66/AMA-1) from the simian parasite Plasmodium knowlesi was protective
      in rhesus monkeys suggested that the 83kDa P. falciparum equivalent (PF83/AMA-1)
      should be investigated for protective effects in humans. Here we briefly review
      pertinent comparative data, and describe the use of an eukaryotic full length
      recombinant PF83/AMA-1 molecule to develop a sensitive ELISA for the
      determination of serological responses in endemic populations. The assay has
      revealed surprisingly high levels of humoral response to this quantitatively
      minor antigen. We also show that PK66/AMA-1 inhibitory mAb's are active against
      merozoites subsequent to release from schizont-infected red cells, further
      implicating AMA-1 molecules in red cell invasion.

PMID- 7565136
TI  - Immunogenicity of multiple antigen peptides containing Plasmodium vivax CS
      epitopes in BALB/c mice.
AB  - Multiple antigen peptide systems (MAPs) allow the incorporation of various
      epitopes in to a single synthetic peptide immunogen. We have characterized the
      immune response of BALB/c mice to a series of MAPs assembled with different B and
      T cell epitopes derived from the Plasmodium vivax circumsporozoite (CS) protein.
      A B-cell epitope from the central repeat domain and two T-cell epitopes from the
      amino and carboxyl flanking regions were used to assembled eight different MAPs.
      An additional universal T cell epitope (ptt-30) from tetanus toxin protein was
      included. Immunogenicity in terms of antibody responses and in vitro T lymphocyte
      proliferation was evaluated. MAPs containing B and T cell epitopes induced high
      titers of anti-peptides antibodies, which recognized the native protein on
      sporozoites as determined by IFAT. The antibody specificity was also determined
      by a competitive inhibition assay with different MAPs. A MAP containing the B
      cell epitope (p11) and the universal epitope ptt-30 together with another
      composed of p11 and the promiscuous T cell epitope (p25) proved to be the most
      immunogenic. The strong antibody response and specificity for the cognate protein
      indicates that further studies designed to assess the potential of these proteins
      as human malaria vaccine candidates are warranted.

PMID- 7565137
TI  - A novel merozoite surface antigen of Plasmodium falciparum (MSP-3) identified by
      cellular-antibody cooperative mechanism antigenicity and biological activity of
      antibodies.
AB  - We report the identification of a 48kDa antigen targeted by antibodies which
      inhibit Plasmodium falciparum in vitro growth by cooperation with blood monocytes
      in an ADCI assay correlated to the naturally acquired protection. This protein is
      located on the surface of the merozoite stage of P. falciparum, and is detectable
      in all isolates tested. Epidemiological studies demonstrated that peptides
      derived from the amino acid sequence of MSP-3 contain potent B and T-cell
      epitopes recognized by a majority of individuals living in endemic areas.
      Moreover human antibodies either purified on the recombinant protein, or on the
      synthetic peptide MSP-3b, as well as antibodies raised in mice, were all found to
      promote parasite killing mediated by monocytes.

PMID- 7565138
TI  - Advances toward the development of an asexual blood stage MSP-1 vaccine of
      Plasmodium vivax.

PMID- 7565139
TI  - Present development concerning antimalarial activity of phospholipid metabolism
      inhibitors with special reference to in vivo activity.
AB  - The systematic screening of more than 250 molecules against Plasmodium falciparum
      in vitro has previously shown that interfering with phospholipid metabolism is
      lethal to the malaria parasite. These compounds act by impairing choline
      transport in infected erythrocytes, resulting in phosphatidylcholine de novo
      biosynthesis inhibition. A thorough study was carried out with the leader
      compound G25, whose in vitro IC50 is 0.6 nM. It was very specific to mature
      parasites (trophozoites) as determined in vitro with P. falciparum and in vivo
      with P. chabaudi -infected mice. This specificity corresponds to the most intense
      phase of phospholipid biosynthesis activity during the parasite cycle, thus
      corroborating the mechanism of action. The in vivo antimalarial activity (ED50)
      against P. chabaudi was 0.03 mg/kg, and a similar sensitivity was obtained with
      P. vinckei petteri, when the drug was intraperitoneally administered in a 4 day
      suppressive test. In contrast, P. berghei was revealed as less sensitive (3- to
      20-fold, depending on the P. berghei-strain). This difference in activity could
      result either from the degree of synchronism of every strain, their invasion
      preference for mature or immature red blood cells or from an intrinsically lower
      sensitivity of the P. berghei strain to G25. Irrespective of the mode of
      administration, G25 had the same therapeutic index (lethal dose 50 (LD50)/ED50)
      but the dose to obtain antimalarial activity after oral treatment was 100-fold
      higher than after intraperitoneal (or subcutaneous) administration. This must be
      related to the low intestinal absorption of these kind of compounds.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7565140
TI  - PCR characterization of isolates from various endemic areas: diversity and turn
      over of Plasmodium falciparum populations are correlated with transmission.

PMID- 7565141
TI  - Infected erythrocyte choline carrier inhibitors: exploring some potentialities
      inside Plasmodium phospholipid metabolism for eventual resistance acquisition.
AB  - We have developed a model for designing antimalarial drugs based on interference
      with an essential metabolism developed by Plasmodium during its intraerythrocytic
      cycle, phospholipid (PL) metabolism. The most promising drug interference is
      choline transporter blockage, which provides Plasmodium with a supply of
      precursor for synthesis of phosphatidylcholine (PC), the major PL of infected
      erythrocytes. Choline entry is a limiting step in this metabolic pathway and
      occurs by a facilitated-diffusion system involving an asymmetric carrier
      operating according to a cyclic model. Choline transport in the erythrocytes is
      not sodium dependent nor stereospecific as demonstrated using stereoisomers of
      alpha and beta methylcholine. These last two characteristics along with distinct
      effects of nitrogen substitution on transport rate demonstrate that choline
      transport in the infected erythrocyte possesses characteristics quite distinct
      from that of the nervous system. This indicates a possible discrimination between
      the antimalarial activity (inhibition of choline transport in the infected
      erythrocyte) and a possible toxic effect through inhibition of choline entry in
      synaptosomes. Apart from the de novo pathway of choline, PC can be synthesized by
      N-methylation from phosphatidylethanolamine (PE). There is a de novo pathway for
      PE biosynthesis from ethanolamine in infected cells but phosphatidylserine (PS)
      decarboxylation also occurs. In addition, PE can be directly and abundantly
      synthesized from serine decarboxylation into ethanolamine, a pathway which is
      absent from the host. The variety of the pathways that exist for the biosynthesis
      of one given PL led us to investigate whether an equilibrium can occur between
      all PL metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565143
TI  - Enhancing the participation and independence of students with severe physical and
      multiple disabilities in performing community activities.
AB  - The effectiveness of a multi-element approach derived from factors to increase
      self-determination of middle- and high-school-age students with physical and
      multiple disabilities was examined. The approach includes equipment and
      performance adaptations, brief in-school simulation training, and instruction and
      support for parents and home assistance providers. The intervention was
      instituted with 3 students; a multiple baseline design was used. Student
      participation and independence dramatically increased after the intervention.
      Results suggest that this approach may be one solution to providing students with
      both inclusive education and community skill and activity instruction. The impact
      of the intervention on student self-determination was discussed.

PMID- 7565142
TI  - Transport pathways in the malaria-infected erythrocyte: characterization and
      their use as potential targets for chemotherapy.
AB  - The intraerythrocytic malarial parasite is involved in an extremely intensive
      anabolic activity while it resides in its metabolically quiescent host cell. The
      necessary fast uptake of nutrients and the discharge of waste product, are
      guaranteed by parasite-induced alterations of the constitutive transporters of
      the host cell and the production of new parallel pathways. The membrane of the
      host cell thus becomes permeable to phospholipids, purine bases and nucleosides,
      small non-electrolytes, anions and cations. When the new pathways are
      quantitatively unimportant, classical inhibitors of native transporters can be
      used to inhibit parasite growth. Several compounds were found to effectively
      inhibit the new pathways and consequently, parasite growth. The pathways have
      also been used to introduce cytotoxic agents. The parasitophorous membrane
      consists of channels which are highly permeable to small solutes and display no
      ion selectivity. Transport of some cations and anions across the parasite
      membrane is rapid and insensitive to classical inhibitors, and in some cases it
      is mediated by specific antiporters which respond to their respective inhibitors.
      Macromolecules have been shown to reach the parasitophorous space through a duct
      contiguous with the host cell membrane, and subsequently to be endocytosed at the
      parasite membrane. The simultaneous presence of the parasitophorous membrane
      channels and the duct, however, is incompatible with experimental evidences. No
      specific inhibitors were found as yet that would efficiently inhibit transport
      through the channels or the duct.

PMID- 7565144
TI  - Thioridazine withdrawal-induced behavioral deterioration treated with clonidine:
      two case reports.
AB  - Neuroleptic withdrawal reactions have significant clinical and medicolegal
      implications for individuals with developmental disabilities. Behavioral
      deterioration following neuroleptic taper can represent (a) relapse of a mental
      illness, (b) and anticholinergic rebound reaction, (c) tardive akathisia, and (d)
      possibly a supersensitivity psychosis. Such reactions may preclude the
      discontinuation of neuroleptic drug therapy, even in the absence of a drug
      responsive psychiatric illness. In this report, the case histories of two
      individuals who experienced a thioridazine (Mellaril) withdrawal-induced
      behavioral deterioration were presented. Both reactions were characterized by
      anxiety and insomnia, and the patients' symptoms were relieved by uncontrolled
      treatment with clonidine (Catapres) therapy. Evidence for adrenergic
      hyperactivity as a mediating event was presented.

PMID- 7565145
TI  - African American families, religion, and disability: a conceptual framework.
AB  - In recent years, there has been considerable discussion of the impact of factors
      such as religion and ethnicity on the adjustment of families who have a child
      with disabilities. The role of religion is particularly relevant for African
      American families because of its historic influence on basic social and cultural
      values of this ethnic group. In this paper we explored issues of religion,
      disability, and ethnicity, with emphasis on how these factors relate to
      adjustment for families, particularly African American families. Findings
      gathered from diverse literature sources are reflected in a proposed framework to
      guide future research and policy development.

PMID- 7565146
TI  - From paper tigers to consumer-centered quality assurance tools: reforming
      incident-reporting systems.
AB  - A practical framework for program administrators seeking to improve the
      effectiveness of their incident reporting and investigation procedures and
      practices was provided. Too often, these systems, which are designed by outside
      parties, are viewed by program administrators as instruments of risk exposure
      rather than viable tools for risk management and quality improvement. Program
      administrators were encouraged to take control of their incident-reporting
      systems by transforming them into viable consumer-centered quality assurance
      tools to meet the quality improvement needs of their own program. Specific
      performance indicators for effective systems were proposed, including consumer
      centeredness; accountable reporting; thorough fact-finding; and prompt
      identification and implementation of corrective actions, fairness, and cost
      effectiveness.

PMID- 7565147
TI  - Grandparents as a source of support for parents of children with disabilities: a
      brief report.
AB  - Measures of emotional adjustment and perceived emotional and instrumental support
      by grandparents were administered to parents of young children with developmental
      disabilities. A significant positive correlation between paternal adjustment and
      grandparent support was found. Grandparents' most frequent forms of assistance
      were babysitting and buying clothing. These results were discussed relative to
      the importance of grandparents as a source of support to families with a child
      who has a disability.

PMID- 7565148
TI  - Family-centered/interdisciplinary team approach to working with families of
      children who have mental retardation.
AB  - Working with children who have mental retardation and their families is
      challenging and rewarding. When these children also have behavioral/psychiatric
      problems, the challenge is far greater. An interdisciplinary team is needed for
      comprehensive assessment, treatment, and management in order to be successful in
      accomplishing goals, providing continuity of care, and supporting the family in
      the community. In this paper we focused on the interdisciplinary team concept
      blended with the family-centered approach in a psychiatric setting and provided a
      case study of a family who had a child diagnosed with mental retardation, autism,
      and severe behavior problems. Practical suggestions were given to demonstrate the
      implementation of a family-centered/interdisciplinary team approach.

PMID- 7565149
TI  - The law hath not been dead: protecting adults with mental retardation from sexual
      abuse and violation of their sexual freedom.
AB  - The extent to which three professional groups (law enforcement officers,
      licensing personnel, and sex educators/counselors) utilize legally relevant
      criteria when assessing the sexual abuse of an adult with mental retardation was
      examined. Subjects were randomly assigned to one of four experimental conditions
      that varied in terms of the ability of a woman with mental retardation to
      understand concepts involving the nature and consequences and right of volition
      in a sexual relationship. The results indicated significant effects for both
      treatment condition and group. Thus, more explicit, standardized criteria should
      be developed for professionals to utilize when assessing consent involving
      possible sexual abuse of adults with mental retardation.

PMID- 7565151
TI  - Beyond consequences.

PMID- 7565150
TI  - Inclusionary standard for determining sexual consent for individuals with
      developmental disabilities.

PMID- 7565152
TI  - Midwifery provided services under attack again.

PMID- 7565153
TI  - Costs of intrapartum care in a midwife-managed delivery unit and a consultant-led
      labour ward.
AB  - OBJECTIVE: to investigate whether there are differences between the cost of
      intrapartum care for women at low obstetric risk in a midwife-managed labour and
      delivery unit and that in a consultant-led labour and delivery ward. DESIGN: cost
      analysis based on the findings of a randomised controlled trial comparing two
      alternative types of intrapartum care. SETTING: Aberdeen Maternity Hospital,
      Grampian. SUBJECTS: the number of women 'booked' for care in the Midwives' Unit
      in a standard year and a comparable group of women cared for in the consultant
      led labour ward. PRIMARY OUTCOME MEASURE: the cost 'outcome' is the extra (or
      reduced) cost per woman resulting from the introduction of a midwife-managed
      delivery unit. FINDINGS: the baseline extra cost of the introduction of the
      Midwives' Unit was found to be 40.71 pounds per woman. Depending on the scenario
      used, this ranged from a cost saving of 9.74 pounds per woman to an additional
      cost of 44.23 pounds per woman. CONCLUSIONS: this study has shown that, in terms
      of costs incurred during the intrapartum period, the marginal cost of caring for
      women at low obstetric risk alongside women at high obstetric risk in a standard
      labour ward is small. However, the impact of establishing a separate midwife
      managed delivery unit, requiring an increase in midwifery staffing levels, can be
      significant.

PMID- 7565154
TI  - Changes in midwives' attitudes to their professional role following the
      implementation of the midwifery development unit.
AB  - OBJECTIVE: to examine changes in midwives' attitudes to their professional role
      following the implementation of the midwifery development unit (MDU). DESIGN:
      prospective cohort study. SETTING: the MDU is based at a major teaching hospital
      in Glasgow, UK. The MDU midwives provide care via a new self-rostering system
      which is intended to improve continuity of care. Midwives aim to provide total
      care for each woman from the antenatal period through delivery and the postnatal
      period. PARTICIPANTS: 21 midwives who joined the MDU were compared with a group
      of 64 midwives at the hospital who were also eligible and who continued in their
      usual pattern of work (non-MDU midwives). MEASUREMENTS: an audit questionnaire
      was distributed to MDU and non-MDU midwives prior to the implementation of the
      unit and about 15 months afterwards. In addition, the MDU midwives were sent the
      questionnaire every three months. Extra questions were added at each time period
      in order to identify specific problems. This information was then fed back to the
      midwifery management team to aid in the planning and implementation of the care
      programme. FINDINGS: the MDU midwives experienced a significant positive change
      in attitudes; no significant change was evident for the non-MDU group. There was
      no evidence of increased stress in the MDU midwives. In general, both groups of
      midwives had positive attitudes towards the unit and felt that MDU-style care had
      a role to play in the future provision of maternity care. A number of areas of
      concern were also highlighted, such as the system of liaison with colleagues.
      CONCLUSIONS: innovative models of midwifery care such as an MDU can have a
      positive impact on midwives' attitudes towards their professional role.
      IMPLICATIONS FOR PRACTICE: if change is managed in a systematic manner which
      involves the midwives, it may be possible to increase midwives' professional
      satisfaction, while at the same time minimising any negative effects such as
      increased stress.

PMID- 7565156
TI  - Women's perceptions of childbirth and childbirth education before and after
      education and birth.
AB  - OBJECTIVE: to illuminate women's perceptions of childbirth and childbirth
      education before and after education and birth. DESIGN: qualitative, using tape
      recorded interviews to collect data. Interpretation was performed from
      Antonovsky's concept sense of coherence. SETTING: childbirth education, a part of
      parent education in Sweden. PARTICIPANTS: eleven women expecting their first
      child, where the pregnancy was planned and normal MEASUREMENTS AND FINDINGS: the
      development of perceptions of childbirth and childbirth education was described.
      The women adopted the content of the education in different ways. Fear as well as
      unreflected knowledge seemed to block acquisition of new knowledge. Factors which
      contributed to a childbirth experience worse than expected were lack of or
      inconsistent information. Increased knowledge about childbirth and experiences of
      confirmation during childbirth contributed to a good or better experience than
      expected. KEY CONCLUSION: any model of childbirth education which does not take
      into consideration the individual woman's perceptions of childbirth and
      childbirth education seems to be inadequate. IMPLICATIONS FOR PRACTICE: the
      findings stress the importance of individual assessment of expectations of and
      experiences of childbirth education. Consistency in information given before and
      during childbirth supports a sense of comprehensibility, manageability and
      meaningfulness.

PMID- 7565155
TI  - The experience of labour: a perspective from those receiving care in a midwife
      led unit.
AB  - AIM: to elucidate the experience of labour for those receiving any aspect of care
      in a midwife-led unit. PARTICIPANTS: a total of 32 women and six partners who
      were interviewed during the postnatal period, either prior to discharge from the
      unit or between three and five months following delivery. METHOD: in-depth
      focused interviews were taped, transcribed, and analysed using a grounded theory
      approach to identify common categories of experience. FINDINGS: the core category
      to emerge was the balance of perceived control and perceived support. Sub
      categories included feeling informed, having options and choices, a supportive
      environment and someone to trust and give confidence. Continuity of care was
      found not to be an option for those whose care was transferred during pregnancy
      or labour. CONCLUSIONS: staffing levels which provide immediate access to the
      support of the midwife throughout labour enhance personal control. Those with the
      greatest need for support and continuity of care and carer are among those least
      likely to receive it.

PMID- 7565157
TI  - A comparison of attenders at antenatal classes in the voluntary and statutory
      sectors: education and organisational implications.
AB  - OBJECTIVE: this study sought to identify whether differences existed in the
      demographic details of clients attending each of three types of antenatal
      classes: those provided at a large inner city hospital, and those provided in the
      voluntary sector by National Childbirth Trust (NCT) and Active Birth teachers.
      The aim was to establish whether there is an overlap in provision of antenatal
      education which might warrant a rationalisation of services. DESIGN: a survey was
      conducted using questionnaires which asked for basic demographic details.
      SETTING: the questionnaires were distributed at antenatal classes held in the
      hospital and in the venues used by the lay teachers (generally their homes).
      PARTICIPANTS: these included 78 primiparae attending 'couples' classes at the
      hospital, 36 primiparae attending NCT classes and 25 primiparae attending Active
      Birth classes. FINDINGS: the women in the three groups were largely similar in
      terms of being older than the national average for childbearing women, middle
      class and affluent as measured by car-ownership. Women from social classes 4 and
      5 and very young women were almost entirely unrepresented. Twenty-three per cent
      of hospital class attenders, 61% of NCT attenders and 48% of Active Birth
      attenders were also going to a second set of antenatal classes, suggesting a
      considerable duplication of effort on behalf of childbirth educators. KEY
      CONCLUSIONS: liaison between the voluntary and statutory sectors could lead to a
      more rational deployment of childbirth educators for the group of women currently
      attending antenatal classes, thus freeing midwives for one-to-one information
      giving or alternative educational provision for women who do not now attend
      formal classes and who may be considered at risk.

PMID- 7565158
TI  - A case-control study of maternal nutrition and neural tube defects in Northern
      Ireland.
AB  - OBJECTIVE: to compare dietary intake and biochemical indices of nutritional
      status in women following birth of a baby/termination of a pregnancy affected by
      neural tube defect (NTD) and women with a normal baby. DESIGN: quantitative,
      using case control methods. SETTING: dietary records were completed by women in
      their own home, blood samples were taken in the local health centres.
      PARTICIPANTS: 15 women referred to the study following an affected pregnancy
      (subjects), matched with 15 women whose pregnancy outcome was normal (controls).
      MEASUREMENTS AND FINDINGS: 7-day weighed dietary records indicated no
      statistically significant differences in nutrient intake but a tendency for lower
      fruit and vegetable consumption in subjects than in controls. Biochemical
      analysis of nutritional status showed that levels of serum vitamin B12 were
      significantly lower in subjects, and activities of two of the nucleotide salvage
      pathway enzymes were significantly higher. KEY CONCLUSIONS: the findings are
      consistent with the findings of other research on NTD and the metabolism of
      folate and vitamin B12. IMPLICATIONS FOR PRACTICE: this study, and other research
      in this area, has implications for health professionals, including midwives with
      their particular involvement in prenatal care, and also highlights the need for a
      clearer focus on nutrition in nursing and midwifery education.

PMID- 7565159
TI  - 1995 Michigan State Medical Society membership directory issue.

PMID- 7565160
TI  - Physicians must provide auxiliary aids/services to assure effective communication
      with hearing impaired patients.

PMID- 7565161
TI  - Visits to three POs provide valuable information.

PMID- 7565162
TI  - To be or not to be an employed physician. Physicians have more choices than they
      may think.

PMID- 7565163
TI  - Changes in risk management on the way.

PMID- 7565165
TI  - Surfing the Internet.
AB  - More physicians are surfing the Internet than ever before, thanks to the recent
      launch of MSMSNET, the Michigan State Medical Society's new online service for
      physician members. If words like World Wide Web, E-mail, and Hypertext links send
      you into a state of confusion, then read on. This month's cover story discusses
      MSMS's launch into the information superhighway and training programs MSMS has in
      store for physician members. Also included is an examination of the Internet-
      past, present and future--by the president of Voyager Information Networks, Inc.,
      a Michigan corporation specializing in Internet services for Michigan trade
      groups and other organizations, including MSMS. This cover story marks the
      beginning of a series of articles on the Internet which will appear in future
      issues of Michigan Medicine. Hop on board and enjoy the ride!

PMID- 7565166
TI  - The birth of the Internet: it's been around longer than you may have thought.
AB  - The Internet just keeps on growing. The handful of computers linked in 1969 has
      grown to nearly 5 million today. Today's reported 30 million Internet users
      worldwide is projected to grow to 100 million within five years.

PMID- 7565164
TI  - Michigan tax changes: the impact on you and your practice.
AB  - Governor Engler and the Legislature have been very active over the last year
      enacting numerous tax changes that have affected both your individual and your
      practice's "bottom lines." This article will summarize these changes both for
      your Michigan personal income tax and for the Single Business Tax (SBT). The SBT
      changes are illustrated later in the article by comparing the SBT liability with
      and without the impact of the new laws, as they would impact typical solo
      practitioners; a two-person practice; and a physicians group practice.

PMID- 7565167
TI  - Medical mission to the Philippines and Thailand an ambitious project.

PMID- 7565168
TI  - Bridging the worlds of organized medicine and public health. A conversation with
      Michigan's chief medical officer Ronald M. Davis, MD. Interview by M. Susan Raef.

PMID- 7565169
TI  - Human regulator of complement activation (RCA) gene family proteins and their
      relationship to microbial infection.

PMID- 7565170
TI  - Identification of phosphocholine-containing glycoglycerolipids purified from
      Mycoplasma fermentans-infected human helper T-cell culture as components of M.
      fermentans.
AB  - Previously, we have reported the occurrence of novel phosphocholine-containing
      glycoglycerolipids (GGPLs: GGPL-I and GGPL-III) in human helper T-cell (MT-4 cell
      line) (Mustuda et al, Glycoconjugate J. 10:340). However, the GGPLs disappeared
      from the MT-4 after treatment with an antimycoplasma agent. This disappearance
      suggested the involvement of microorganisms in the GGPL expression. In this
      paper, we show that the novel lipids are components of Mycoplasma fermentans
      itself. The supernatant fluid of the antimycoplasma agent-untreated Mt-4 cell
      culture produced mycoplasma-like colonies on PPLO agar plates, and PCR and
      immunological methods revealed the presence of M. fermentans. GGPLs were
      expressed again in the treated Mt-4 cells after infection with the isolated M.
      fermentans. The isolated M. fermentans had glycoglycerolipids corresponding to
      GGPL-I and GGPL-III. Thin-layer chromatography-mass spectrometry and
      immunological analyses showed that these glycoglycerolipid which were derived
      from the isolated M. fermentans were identical with GGPL-I and GGPL-III
      previously obtained. This is the first report that shows mycoplasma has
      phosphocholine-containing glycoglycerolipids.

PMID- 7565171
TI  - Typing of Staphylococcus epidermidis colonizing in human nares by pulsed-field
      gel electrophoresis.
AB  - From the nares of 11 healthy adults, 253 strains of coagulase negative
      staphylococcus were isolated and 88% of them were identified as Staphylococcus
      epidermidis using the API STAPH system. Chromosomal DNA fingerprinting of the
      isolated strains revealed that each person carried multiple types of S.
      epidermidis in his or her nares. The colonization of the strains was not stable;
      the types of the isolates changed in the first and the second examinations 5
      months apart. The results contrasted with previous findings in which only one
      strain of S. aureus colonized persistently in the nares of healthy adults.

PMID- 7565172
TI  - Heat shock proteins in the human periodontal disease process.
AB  - The production of HSP by periodontopathic Gram-negative bacteria was examined by
      SDS-PAGE, two dimensional gel electrophoresis, and Western blotting using
      monoclonal antibodies against HSPs. Strains of Actinobacillus
      actinomycetemcomitans, Eikenella corrodens, Fusobacterium nucleatum, Prevotella
      intermedia, Prevotella nigrescens, Prevotella melaninogenica, and Treponema
      socranskii species produced HSP which reacted with anti-Yersinia enterocolitica
      HSP 60 and/or mycobacterial 65-kDA HSP monoclonal antibodies. It found that
      gingival homogenate samples from patients with adult periodontitis reacted with
      anti-human HSP were also found in a serum sample from a periodontitis patient.
      The present study suggests that HSPs are implicated in human periodontal disease
      process.

PMID- 7565174
TI  - Seroepidemiological survey of Bartonella (Rochalimaea) henselae in domestic cats
      in Japan.
AB  - A total of 199 domestic cat serum samples from 3 geographical areas
      (northeastern, central and southwestern) of Japan collected between 1992 and 1994
      were examined for serum antibody against Bartonella henselae using an
      immunofluorescent assay. The antibody prevalence was 15.1% (30/199). A
      significant difference in the prevalence of B. henselae antibody was observed
      between the northeastern area (6.3%:3/48) and the central area (22.0:13/59) in
      Japan. There was no significant difference between the average age of
      seropositive cats (4.39 +/- 3.26 years) and that of seronegative cats (4.03 +/-
      3.84 years), and also between the frequency of seropositive male cats
      (16.5%:15/91) and that of seropositive female cats (11.8:9/76). This is the first
      report of B. henselae antibodies in cats in Japan

PMID- 7565173
TI  - Electron microscopic examination of factors influencing the expression of
      filamentous surface structures on clinical and environmental isolates of
      Aeromonas veronii Biotype sobria.
AB  - Strains of Aeromonas veronii biotype sobria isolated from clinical and
      environmental sources were examined for their expression of surface structures
      under a variety of culture conditions. When grown on solid media at 37 degrees C,
      more than 95% of bacteria from the majority of strains isolated from human
      diarrheal feces and chicken carcasses were non-piliated or expressed only a few
      pili of long, flexible morphology per cell. Strains isolated from water or other
      foods were much more likely to express pili. Heavily piliated strains (all
      sources) possessed pili of several morphological types, including long, flexible
      pili of varying widths and rigid pili of varying lengths. Expression of Pili was
      favored by growth at temperatures ca. 20 degrees C and below and growth in liquid
      medium. Most fecal strains expressed some pili under these conditions. In
      addition, other surface structures (fibrillar aggregates, fibrillar networks
      bundle-forming pili) were seen on some strains from most sources. These were also
      seen most frequently when bacteria were grown in liquid media at temperatures ca.
      20 degrees C and below. Pili expression was not dramatically influenced by growth
      under anaerobic conditions, or in iron-depleted media, or by combinations of the
      above conditions. The role of the above surface structures in Aeromonas
      pathogenicity remains to be elucidated.

PMID- 7565175
TI  - Correlation between the presence of virulence-associated genes as determined by
      PCR and actual virulence to mice in various strains of Listeria spp.
AB  - Five chromosomal genes, prfA, plcA, hlyA, mpl and plcB, are implicated in the
      virulence of Listeria monocytogenes and some of these genes have been used for
      the identification of bacteria by polymerase chain reaction (PCR). Using 6
      strains of L. monocytogenes and 3 L. innocua strains, the relationship was
      examined between the presence of five virulence-associated genes and actual
      virulence to mice in terms of 50% lethal dose (LD50), bacterial viability in the
      organ of infected mice and the intracellular growth in cultured macrophages. None
      of the five genes could be amplified by PCR in all the L. innocua strains and
      they were actually avirulent to mice. All L. monocytogenes strains were shown to
      be virulent and to have intact virulence-associated genes except for the strain
      ATCC15313. This particular strain was revealed to be avirulent and defective in
      hlyA and plcA in PCR amplification. It was suggested that PCR detection of genes
      prfA, mpl, or plcB may not be sufficient to detect virulent strains of L.
      monocytogenes. It appeared that the ability to produce listeriolysin O (LLO),
      which is encoded by hlyA, was critical for the expression of virulence regardless
      of the amount of LLO produced.

PMID- 7565177
TI  - Isolation of influenza A and B viruses in HeLa cells.
AB  - The HeLa cell line which is one of the most popular cell lines was shown to be
      suitable for isolation of types A (H3N2) and B influenza viruses from throat
      washings of patients. Sixty-nine and 67 out of 147 throat washings taken from
      patients during the period from January to April 1994, were positive for
      influenza A virus in HeLa cells and MDCK cells respectively. Seven out of 10
      throat washings taken between January and March, 1993, were positive for
      influenza B virus in MDCK. Of these 7, 4 were also positive for HeLa cells.

PMID- 7565176
TI  - Sheep red blood cell instillation at palatine tonsil effectively induces specific
      IgA class antibody in saliva in rabbits.
AB  - We have shown that the palatine tonsil effectively incorporates exogenous foreign
      substances instilled at its surface. It is not clear whether antigen-specific IgA
      can be induced by the instillation. Sheep red blood cells (SRBC) were instilled
      at the palatine tonsil every three days as the antigen, and the agglutination
      titer of specific IgA in saliva was examined. Nasal or intragastric
      administration, which have been shown to induce specific antibody in saliva, were
      done as control experiments. Anti-SRBC antibody in saliva from the tonsillar
      instillation group was detected in the second week, and the agglutination titer
      reached a maximum in the 6th week after instillation. The maximum titers in the
      tonsillar instillation group and nasal administration group were 16 (P < 0.01, n
      = 7) and 4 times (P < 0.01, n = 7) higher, respectively, than that in the
      intragastric administration group. In the tonsillar instillation group, the
      number of specific antibody- producing cells per 10(5) lymphocytes was the
      highest in the parotid glands compared with the lymphoid tissues such as the
      retropharyngeal lymph nodes, nasal mucosa, mesenteric lymph nodes, Peyer's
      patches, cervical lymph nodes, palatine tonsil and spleen. In the nasal
      administration group, the number of lymphocytes was the highest in the nasal
      mucosa. The results indicate that tonsillar instillation was more effective than
      nasal administration in inducing specific iIgA in saliva.

PMID- 7565178
TI  - A flow cytometric assay reveals a suppression of phagocytosis by rabbit defensin
      NP-3A in mouse peritoneal macrophages.
AB  - Phagocytosis of fluorescein isothiocyanate (FITC)-labeled polystyrene
      microparticles by peritoneal macrophages from thioglycollate-elicited mice was
      examined by means of flow cytometry (FCM). This assay revealed that rabbit
      defensin NP-3A suppressed the phagocytosis in a dose-dependent manner. The
      present results suggest that NP-3 released from neutrophils is one of the
      mediators which modulates the activity of macrophages in response to infection.

PMID- 7565179
TI  - Rheumatic heart disease: how big is the problem?

PMID- 7565180
TI  - Pattern of acute rheumatic fever in a local teaching hospital.
AB  - Hospital records of children admitted to the department of Paediatrics,
      University Hospital, Kuala Lumpur, from January 1981 to December 1990, who were
      diagnosed to have acute rheumatic fever (ARF) were studied. 134 children
      satisfied the Jones' modified criteria, thus giving a hospital incidence of
      21.2/100,000 paediatric admission per year, of which incidence of first attack
      was 15.8/100,000 per year and recurrent attack was 5.38/100,000 per year. The M:F
      ratio is 1.39:1. Majority of cases occur in the 6-11 years age group with 6 cases
      encountered below the age of 5. The Indians had a higher relative risk to develop
      both the first acute attack as well as recurrences with a relative risk of 2.4
      and 4.10 respectively as compared to the Malays. Majority of the patients,
      irrespective of the ethnic group, came from families with low income.

PMID- 7565181
TI  - Early congenital syphilis--a continuing problem in Malaysia.
AB  - Between February 1990 and May 1993, 13 cases of early congenital syphilis (ECS)
      were managed in the Paediatrics Unit, University Hospital, Kuala Lumpur. Twelve
      mothers were unbooked with 10 inborn babies. Only one mother had antenatal
      booking at this hospital but she defaulted antenatal follow-up. Several risk
      factors associated with ECS were identified: inadequate or no prenatal care
      (5/13), failure to repeat a serological test for syphilis in the third trimester
      when it was tested negative at first booking (5/13), sexual promiscuity,
      substance abuse and a past history of contracting sexually transmitted disease.
      All 10 mothers who had their serological test repeated at delivery were found to
      have a positive VDRL and TPHA. Adequate antenatal care early referral of
      infected, expectant mothers for treatment, and a repeat serological test for
      syphilis could have prevented these cases of ECS.

PMID- 7565182
TI  - Comparison of three different methods in the assessment of neutrophil function.
AB  - Three different methods to measure the oxidative respiratory burst of neutrophils
      were performed. Of the three, the chemiluminescence technique was observed to be
      the most sensitive among them. The strong statistical correlation and an
      acceptable agreement between chemiluminescence with that of the killing assay
      provides evidence for using the chemiluminescence assay as an alternative method
      of detecting gross defects of neutrophil respiratory burst killing assays.

PMID- 7565185
TI  - Infant feeding practices and attitudes of mothers in Kelantan towards
      breastfeeding.
AB  - The incidence of breastfeeding among 96 mothers (88/96 were Malays) who were
      attending various clinics at Universiti Sains Malaysia Hospital and Kota Bharu
      General Hospital was about 95%. The feeding patterns show that about 72% of
      mothers gave mixed feedings (breastmilk plus infant formula) while only 30% gave
      exclusive breastmilk to their infants in the first six months. Two main reasons
      for giving mixed feedings were that mothers had to start working soon after
      giving birth and reported "insufficient milk". Mixed feedings were seen to be
      more prevalent in the higher income group mothers (> RM1000 per month). About 64%
      of them who breastfed their child continued to do so beyond 6 months. Regarding
      their knowledge on breastfeeding, most mothers (98%) knew that breastmilk is good
      for baby's health, economical, strengthens bonding between mother and child, and
      was sufficient for the sustenance of the baby. However, when asked about
      colostrum, 66% of mothers who breastfed their child threw away the colostrum
      before feeding; some of the reasons given were that colostrum is dirty, and not
      suitable for the baby's health and it might cause some diseases.

PMID- 7565183
TI  - Rice starch low sodium oral rehydration solution (ORS) in infantile diarrhoea.
AB  - The relative efficacy and incidence of hypernatremia of a rice starch based low
      sodium (sodium of 60 mmol/L) oral electrolyte solution was compared to the
      standard WHO oral rehydration solution (ORS; sodium 90 mmol/L) in 60 infants with
      non choleragenic acute diarrhoea. Both solutions were found to be equally
      effective in correcting dehydration as determined by the respective post
      hydration weight gain which was 150 +/- 175 gms in the rice starch low sodium ORS
      group and 164 +/- 125 gms in the standard WHO ORS group. However, the mean
      frequency of stools was greater and the duration of stay longer in the WHO ORS
      group compared to the rice starch low sodium group. There were 5 cases of
      hypernatremia in the WHO ORS group as opposed to only one in the rice starch low
      sodium ORS group. The present study shows that a rice starch low sodium ORS was
      as effective as the standard WHO ORS and had a lower incidence of hypernatremia
      in the fluid and electrolyte management of infants with non choleragenic
      diarrhoea.

PMID- 7565184
TI  - Splenorrhaphy: omental pouch.
AB  - This work studies the efficacy of an autogenous viable omental pouch as a means
      of splenorrhaphy for saving the traumatised spleen. One sheep and 9 goat spleens
      were mobilised and their vascular pedicles clamped. All spleens were subjected to
      AAST grade IV trauma. The injured spleens were put into omental pouches and
      manual pressure was applied for 10 minutes after removal of the vascular clamp.
      Bleeding was controlled in 8 animals which became fully active 12-36 hours
      postoperatively. Two animals died, one due to aspiration of gastric contents
      during surgery and the other due to bleeding 24 hours postoperatively. All
      remaining spleens were harvested after 6 weeks. They were surrounded by a fibrous
      capsule and the previously inflicted injuries were easily identifiable. Viable
      omental pouch based on left epiploic vascular pedicle offers itself as a good
      autogenous alternative other methods used for saving the injured spleen. This
      method has been used in two humans so far.

PMID- 7565186
TI  - Anti-lymphocyte globulin therapy in aplastic anaemia--a university hospital
      experience.
AB  - Antilymphocyte globulin (ALG) was given every other day for 5 doses with platelet
      transfusions immediately following ALG administration in 6 patients with aplastic
      anaemia. Four patients responded and 3 durable remissions were achieved. One
      patient relapsed and further treatment with anti-thymocyte globulin and
      cyclosporin also failed. One patient died of Flavobacterium septicaemia 6 days
      after completion of ALG. Our data suggests that using an alternate day regimen, a
      response rate similar to a daily regimen can be obtained.

PMID- 7565187
TI  - Management of patients before, during and after upper gastrointestinal endoscopy.

PMID- 7565190
TI  - "Koro"-like syndrome affecting the tongue--a case report.
AB  - A 52-year-old man presented with a 2-year history of episodic retraction of his
      tongue into the throat with a belief that he will die if the retraction is
      complete. The presentation is similar to koro except that the tongue is involved
      instead of the penis. It appears that retraction taxon can involve other organs
      and may not necessarily be culture bound.

PMID- 7565189
TI  - Osteogenesis Imperfecta and non-accidental injury: problems in diagnosis and
      management.
AB  - It has been noted in the literature that Osteogenesis Imperfecta is frequently
      mistaken for non-accidental injury. This article serves to illustrate the
      difficulty in differentiating between the two conditions and that they can occur
      concomitantly in one patient.

PMID- 7565188
TI  - Acquired haemophilia--a therapeutic challenge.
AB  - Acquired haemophilia is a rare clinical condition arising from the spontaneous
      development of inhibitors to factor VIII. We describe two cases encountered in
      the University Hospital over the past five years. We also review the literature
      and discuss the therapeutic difficulties faced in dealing with patients with high
      levels of inhibitors. In one of these patients we also describe, for the first
      time in this region, a novel method in managing the acute bleeding episode in
      acquired haemophilia using recombinant factor VIIa.

PMID- 7565192
TI  - Pontine myelinolysis following correction of hyponatraemia.
AB  - A patient with severe hyponatreamia secondary to chronic renal failure was
      treated with peritoneal dialysis (PD). On the third day of admission, she
      developed progressive obtundation. Neurological examination showed bilateral
      brisk reflexes with intact brain stem reflexes. Magnetic resonance imaging
      demonstrated patchy demyelination of the pontine area indicating central pontine
      myelinolysis (CPM). Despite supportive measures, the patient died on the
      fifteenth day of admission. The rate of correction of hyponatraemia with
      peritoneal dialysis can be rapid and detrimental to hyponatraemic chronic renal
      failure patients and careful monitoring of serum sodium level is advocated.

PMID- 7565191
TI  - Laboratory acquired murine typhus--a case report.
AB  - A 34-year-old laboratory worker developed murine typhus after an accidental
      splashing of Rickettsia typhi over her right eye and lips. Indirect
      immunoperoxidase test showed a four-fold increase in titre to Rickettsia typhi.
      She responded well to doxycycline.

PMID- 7565193
TI  - Clonorchiasis/opisthorchiasis in Malaysians case reports and review.
AB  - Clonorchiasis and opisthorchiasis are snail-transmitted trematode infections. The
      disease is endemic in many parts of Asia. Local case reports have been
      predominantly in Chinese with a history of travel to endemic countries. Thus far,
      20 cases of liver fluke infestation have been reported in this country. This
      report presents another two cases of clonorchiasis and a case of opisthorchiasis.
      We also briefly review pertinent aspects of the disease.

PMID- 7565194
TI  - Moyamoya disease in Malaysia: two documented cases.
AB  - Moyamoya disease is a rare cause of young strokes. The definitive diagnosis of
      moyamayo disease is made by cerebral angiography. We report two cases of moyamoya
      disease in Malaysia.

PMID- 7565195
TI  - Retroperitoneal malignant fibrous histiocytoma with renal involvement.
AB  - Malignant fibrous histiocytoma is a mesenchymal tumour which can involve the
      genitourinary organs primarily or by secondary extension. Both conditions are
      rare. We report four cases of retroperitoneal malignant fibrous histiocytoma
      involving the kidney by local extension. Diagnosis was difficult because of
      diverse, non-specific clinical features and may only be reached at operation or
      post mortem. Prognosis is poor. Although en bloc tumour resection with
      nephrectomy was possible in two patients, they returned with recurrences.

PMID- 7565196
TI  - Baby walker associated scalding injuries seen at University Hospital Kuala
      Lumpur.
AB  - Baby walker associated injuries are occurring in Malaysia. Most are not noticed
      as paediatricians are more concerned with the treatment of the injury and forget
      the preventive measures required to overcome this problem. We believe that baby
      walkers should be banned in Malaysia as the risks of injury far outweighs any
      benefits. We present 4 cases of baby walker associated scalding injuries.

PMID- 7565197
TI  - Coronary heart disease mortality in peninsular Malaysia.

PMID- 7565198
TI  - Epidural blood patch for post dural puncture headache.

PMID- 7565199
TI  - Hereditary angioedema: report of a family in Malaysia.

PMID- 7565200
TI  - How parents in a rural area of Pekan district, Pahang perceive immunisation.

PMID- 7565201
TI  - Leech, wire and urethra.

PMID- 7565202
TI  - Hospital-acquired infections: a skeleton in the closet of medical progress.

PMID- 7565203
TI  - Shifting medicolegal sands.

PMID- 7565204
TI  - Preventing sports injury remains a challenge.

PMID- 7565205
TI  - Folate, B12 and neural tube defects.

PMID- 7565206
TI  - A prospective audit of total parenteral nutrition at a major teaching hospital.
AB  - OBJECTIVE: To examine patterns of use and clinical outcomes of total parenteral
      nutrition (TPN). DESIGN: A prospective six-month audit (December 1992-June 1993).
      PATIENTS AND SETTING: All inpatients administered TPN at a metropolitan teaching
      hospital during the audit period. MAIN STUDY MEASURES: Process measures included
      data about TPN initiation (bodyweight, period not receiving oral/nasogastric
      feeding, serum albumin level, compliance with hospital guidelines), TPN delivery
      data (kilojoules, and nutrient and electrolyte content), and bases for cessation
      or changes of TPN (biochemistry data, gastric and intestinal function). Outcome
      measures included body mass change, infection rate, detection of biochemical
      abnormalities, and death. RESULTS: During the audit 168 consecutive patients
      received 175 TPN courses. These patients were followed until discharge or death;
      49 patients (29%) died. Intensive care units accounted for 57.7% of TPN use.
      Deviations from approved hospital guidelines for initiation of TPN were common.
      Only a minority of patients were malnourished on objective audit criteria; 18% of
      men and 13% of women were underweight by body mass index criteria and 36% were
      malnourished when serum albumin level (< 30 g/L) was considered. Early initiation
      of TPN outside accepted guidelines was common. Complications included bacteraemia
      (9.1% of patients tested) and catheter-tip sepsis (55.2% of 87 catheters tested).
      Four patients died; line sepsis caused one death and probably a further two. The
      incidence of glucose intolerance was 36.5%, and 25% had markers of abnormal liver
      function. CONCLUSIONS: TPN use is associated with a high risk of morbidity, and a
      1.7% mortality. We recommend better patient selection for TPN, more appropriate
      use of enteral feeding, better infection control procedures, avoidance of
      substrate overload (particularly glucose), and earlier change to enteral
      nutrition.

PMID- 7565207
TI  - Antibiotic resistance among respiratory pathogens in preschool children.
AB  - OBJECTIVE: To determine the prevalence of antibiotic resistance among common
      respiratory pathogens circulating in the community. DESIGN: Survey of common
      respiratory pathogens isolated from nasal discharges. SETTING: 117 childcare
      centres and kindergartens in metropolitan Melbourne between May and July 1991
      1993 and 42 from sociodemographically matching suburbs in Sydney between May and
      July, 1993. SUBJECTS: Children aged six years and under with nasal discharge.
      OUTCOME MEASURES: Resistance to penicillins, erythromycin and tetracycline among
      isolates of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella
      (Branhamella) catarrhalis and Staphylococcus aureus. RESULTS: A total of 2286
      nasal discharge swabs were collected. Amoxycillin resistance was detected in 99
      of 711 isolates of H. influenzae (13.9%) and penicillin resistance in 781 of 834
      isolates of M. catarrhalis (93.6%), 342 of 375 isolates of S. aureus (91.2%), and
      30 of 781 isolates of S. pneumoniae (3.9%). Of 86 strains of H. influenzae type b
      isolated, 20 (23.3%) produced beta-lactamase. Penicillin resistance tended to
      become more common among isolates of H. influenzae and S. pneumoniae during the
      three-year period. CONCLUSION: Antibiotic resistance, mediated by beta-lactamase
      or altered penicillin-binding proteins, among respiratory pathogens carried by
      preschool children was significant and possibly increasing. This highlights the
      impact of prescribed antibiotics in the community and the folly of prescribing
      the limited store of antibiotics for viral infections.

PMID- 7565208
TI  - Catastrophic injuries to the eyes and testicles in footballers.
AB  - OBJECTIVE: To report the occurrence of uncommon but catastrophic eye and testicle
      injuries to rugby league and rugby union footballers in New South Wales. METHODS:
      A retrospective review of players who had permanent football-related injuries and
      who claimed financial compensation from a voluntary sports injury insurance
      scheme from 1978-1994. RESULTS: An average of 100 000 rugby league and rugby
      union players per year were registered with the insurance scheme in NSW. As a
      consequence of playing football, 15 players lost 90%-100% vision in one eye, five
      lost 75% vision in one eye, four lost 50% of vision in one eye and two lost 75%
      vision in both eyes. Eye injuries were caused by "gouging" with fingers, kicks,
      or blows from fists, elbows and knees; five cases appeared to be intentional.
      Fourteen players had testicular injuries: in 11 players this resulted in complete
      loss of one testicle, and in three partial loss of one or both testicles. The
      immediate cause of the injuries to the testicles was kicking and kneeing, usually
      during tackles; at least three of the injuries appeared to be intentional.
      RECOMMENDATIONS: Rules relating to tackles, kicks and other assaults to the head
      or groin should be strengthened and policed. Officials, players, parents and the
      public should be educated to support this.

PMID- 7565209
TI  - General practitioner attitudes to recall systems for cervical screening.
AB  - OBJECTIVES: To document the factors associated with general practitioner (GP) use
      of Pap smear reminder/recall systems and to canvass options for coordinating
      these GP-based systems with similar centrally based schemes. METHODS: A
      questionnaire survey of a random sample of South Australian GPs. RESULTS: 259
      (78%) of 334 GPs returned questionnaires. 117 (45.2%) GPs had practice-based
      reminder/recall systems, with a higher prevalence among metropolitan GPs with a
      computer and who had been in practice for less than 20 years. 91.9% of GPs
      reported that the central register would be of some help in ensuring regular
      cervical screening. 38.2% of the GPs preferred reminder letters from the register
      to be sent to their practice; 27.8% preferred them to be sent directly to women
      and 22.8% opted for letters to be sent from the register via the laboratories to
      their practice. 61.4% of respondents had a method of recording women with
      abnormal smears and 95.6% of these actively recalled such women. CONCLUSION:
      Substantial variation exists in the use of practice-based reminder/recall systems
      among GPs. A central register would assist most GPs by providing a back-up
      reminder service to follow-up women for cervical screening.

PMID- 7565210
TI  - Donor insemination: effects on parents.
AB  - OBJECTIVE: To examine the psychosocial effects of donor insemination on couples.
      DESIGN: Questionnaire survey of couples who had a child by donor insemination at
      four NSW clinics over a 15-year period. RESULTS: Forty-seven per cent of couples
      thought their marriage had improved, while 3% thought their marriage had
      deteriorated as a result of having a child by donor insemination. Seventy-six per
      cent felt it had a positive personal effect and almost all couples had no regrets
      about having a child this way. Over 90% of respondents felt very close to these
      children. In those who also had children not conceived by donor insemination (60
      couples), men were significantly closer to their children by donor insemination
      than to their "other" children (P < 0.001). There was a significant sex
      difference in perceptions of the child's resemblance (P < 0.0001): 61% of women
      thought their child conceived by donor insemination resembled their partner,
      while 89% of men thought the child resembled their partner. Twenty-one per cent
      of couples were concerned about having to tell the child about donor
      insemination. CONCLUSION: Donor insemination can have positive psychosocial
      effects on couples and close relationships exist between the parents and their
      children conceived by donor insemination. The concern about the physical
      appearance of children conceived by donor insemination can be allayed by our
      finding that the majority of couples see a resemblance between the child and
      their partner.

PMID- 7565211
TI  - Helicobacter pylori and gastric neoplasia: evolving concepts.
AB  - There is evidence that Helicobacter pylori infection is associated with gastric
      cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and possibly with
      non-ulcer dyspepsia. Eradication therapy for confirmed H. pylori infection may
      therefore become mandatory in patients with non-ulcer dyspepsia severe enough to
      warrant endoscopy and in first-degree relatives of patients with gastric cancer.
      However, routine treatment of asymptomatic carriers awaits confirmation of the
      association with cancer.

PMID- 7565212
TI  - Amyloid, aluminium and the aetiology of Alzheimer's disease.
AB  - Several lines of evidence suggest that neurotoxic beta A4 amyloid deposits are of
      prime importance in the pathogenesis of Alzheimer's disease. Epidemiologically
      determined risk factors such as Down's syndrome, head injury and apoE allelic
      status can be explained on the basis of this hypothesis. However, there are
      difficulties with the hypothesis--amyloid accumulation may be necessary, but is
      not sufficient to produce the neuronal damage seen in Alzheimer's disease. The
      association between aluminum exposure and Alzheimer's disease remains unproven
      and is considered to be increasingly peripheral to recent developments in our
      understanding of the disease.

PMID- 7565213
TI  - Has informed consent become a legal nightmare?

PMID- 7565214
TI  - Social and legal changes in medical malpractice litigation.

PMID- 7565215
TI  - Position statement on the use of rectal diazepam in epilepsy. Epilepsy Society of
      Australia, the Child Neurology Study Group, the Australian Association of
      Neurologists, and the National Epilepsy Association of Australia.

PMID- 7565216
TI  - The future of medicine: does the profession have a vision?

PMID- 7565217
TI  - Contaminated razor blades as a possible source of hepatitis C virus infection.

PMID- 7565218
TI  - Management of hepatitis C in general practice.

PMID- 7565219
TI  - Repetition strain injury: a 10-year follow-up.

PMID- 7565220
TI  - Transfusions: how many cases of Ross River virus infection do we cause?

PMID- 7565221
TI  - Hazards of transrectal biopsy of prostate.

PMID- 7565222
TI  - Deaths of Australian travellers overseas.

PMID- 7565223
TI  - Transient ischaemic attacks.

PMID- 7565224
TI  - Safe prescribing of methotrexate for rheumatoid arthritis.

PMID- 7565225
TI  - Heat stroke in the city...

PMID- 7565227
TI  - More law, less order.

PMID- 7565226
TI  - Hypoglycaemia, Munchausen's syndrome and pseudoinsulinoma.

PMID- 7565228
TI  - Neurotoxicity from overuse of nitrous oxide.

PMID- 7565229
TI  - Obstetric care in the late 20th century.

PMID- 7565230
TI  - Chronic fatigue syndrome: what's in a name?

PMID- 7565231
TI  - Glaucoma: is there light at the end of the tunnel?

PMID- 7565232
TI  - Parkinson's disease: moving forward.

PMID- 7565233
TI  - Continuity of care by a midwife team versus routine care during pregnancy and
      birth: a randomised trial.
AB  - OBJECTIVE: To compare continuity of care from a midwife team with routine care
      from a variety of doctors and midwives. DESIGN: A stratified, randomised
      controlled trial. PARTICIPANTS AND SETTING: 814 women attending the antenatal
      clinic of a tertiary referral, university hospital. INTERVENTION: Women were
      randomly allocated to team care from a team of six midwives, or routine care from
      a variety of doctors and midwives. MAIN OUTCOME MEASURES: Antenatal, intrapartum
      and neonatal events; maternal satisfaction; and cost of treatment. RESULTS: 405
      women were randomly allocated to team care and 409 to routine care; they
      delivered 385 and 386 babies, respectively. Team care women were more likely to
      attend antenatal classes (OR, 1.73; 95% CI, 1.23-2.42); less likely to use
      pethidine during labour (OR, 0.32; 95% CI, 0.22-0.46); and more likely to labour
      and deliver without intervention (OR, 1.73; 95% CI, 1.28-2.34). Babies of team
      care mothers received less neonatal resuscitation (OR, 0.59; 95% CI, 0.41-0.86),
      although there was no difference in Apgar scores at five minutes (OR, 0.86; 95%
      CI, 0.29-2.57). The stillbirth and neonatal death rate was the same for both
      groups of mothers with a singleton pregnancy (three deaths), but there were three
      deaths (birthweights of 600 g, 660 g, 1340 g) in twin pregnancies in the group
      receiving team care. Team care was rated better than routine care for all
      measures of maternal satisfaction. Team care meant a cost reduction of 4.5%.
      CONCLUSION: Continuity of care provided by a small team of midwives resulted in a
      more satisfying birth experience at less cost than routine care and fewer adverse
      maternal and neonatal outcomes. Although a much larger study would be required to
      provide adequate power to detect rare outcomes, our study found that continuity
      of care by a midwife team was as safe as routine care.

PMID- 7565234
TI  - A preliminary investigation of chlorinated hydrocarbons and chronic fatigue
      syndrome.
AB  - OBJECTIVE: To determine whether serum levels of chlorinated hydrocarbons are
      elevated in patients with chronic fatigue syndrome. METHODS: Chlorinated
      hydrocarbon levels were measured in 22 patients with chronic fatigue syndrome
      (CFS) (as defined by the Centers for Disease Control [CDC]); in 17 patients with
      CFS symptoms whose history of exposure to toxic chemicals excluded them from the
      research definition of CFS; and in 34 non-CFS control subjects matched for age
      and sex. RESULTS: DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) was detected
      in all serum samples at levels over 0.4 ppb. The incidence of hexachlorobenzene
      (HCB) contamination (> 2.0 ppb) was 45% in the CFS group, compared with 21% in
      the non-CFS control group (P < 0.05). The CFS group had a significantly higher
      total organochlorine level (15.9 ppb; SEM, 4.4) than the control group (6.3 ppb;
      SEM, 1.1; P < 0.05). The toxic exposure group also had a higher mean
      organochlorine level (13.6 ppb; SEM, 6.2) than the control group, but the
      difference was not statistically significant. DDE and HCB comprised more than 90%
      of the total organochlorines measured in each of the groups. CONCLUSION: The
      results suggest that recalcitrant organochlorines may have an aetiological role
      in CFS. There were no significant differences in serum organochlorine
      concentrations between CFS patients and chronic fatigue patients with a history
      of toxic chemical exposure. Therefore, exclusion of patients from the CDC
      research definition of CFS on the basis of a reported history of known exposure
      to toxic chemicals is not valid. The role of low-level organochlorine
      bioaccumulation in the development of CFS symptoms requires further
      investigation.

PMID- 7565236
TI  - Early-onset group B streptococcal infections in Aboriginal and non-Aboriginal
      infants. Australasian Study Group for Neonatal Infections.
AB  - OBJECTIVES: To survey early-onset neonatal infections in Australian and New
      Zealand neonatal units and to compare the incidence of group B streptococcal
      (GBS) sepsis among Aboriginal and non-Aboriginal babies. DESIGN: Second year of
      an ongoing longitudinal, prospective study. SETTING: Nine Australian units and
      one New Zealand unit with level 3 neonatal care and one Australian unit with
      level 2 care, between October 1992 and September 1993 inclusive. OUTCOME
      MEASURES: Episodes of early-onset sepsis (within 48 hours of birth), causative
      organisms, mortality, birthweight and gestational age. SUBJECTS: Babies in the
      neonatal units with early-onset systemic sepsis, either born in attached
      maternity hospitals or referred. RESULTS: In the Australian units there were 100
      episodes of early-onset sepsis (incidence among babies born in attached maternity
      hospitals of 2.9 per 1000 live births). GBS was the commonest infecting agent
      (70% of cases) and caused all 12 cases of early-onset meningitis. The mortality
      from early-onset sepsis was 10%. The incidence of GBS sepsis was 1.7 per 1000
      live births in non-Aboriginal babies and 5.2 per 1000 in Aboriginal babies (odds
      ratio, 3.1; 95% confidence interval, 1.4-6.6). CONCLUSIONS: Early-onset GBS
      sepsis is more than three times as common in Aboriginal babies delivered in
      hospital than in non-Aboriginal babies. Four of seven Australian maternity
      hospitals surveyed had no firm policy for reducing the incidence of early-onset
      GBS sepsis. All should urgently consider such a policy.

PMID- 7565235
TI  - The Tay-Sachs disease prevention program in Australia: Sydney pilot study.
AB  - OBJECTIVES: To determine the frequency of heterozygous carriers of the Tay-Sachs
      disease gene in an asymptomatic Ashkenazi Jewish population and to compare the
      acceptability of different community testing strategies. DESIGN: Pilot survey of
      carrier rates and community attitudes. SETTING: Sydney, February 1993 to November
      1994. PARTICIPANTS: 147 self- or medically referred people of Ashkenazi Jewish
      origin were tested. Jewish religious, medical and community organisations and
      leaders were consulted. OUTCOMES: Prevalence of HEXA mutations, client and
      community preference for different testing and reporting strategies. RESULTS:
      Frequency of heterozygous carriers was 1 in 18, with a relative frequency of the
      three major allelic variants similar to that in overseas studies. Most subjects
      were medically referred and preferred individual reporting of their carrier
      status. Community representatives had serious reservations about this strategy
      and few orthodox Jews participated in the study. An alternative strategy was
      developed for future testing. CONCLUSIONS: Frequency of heterozygous carriers of
      the Tay-Sachs disease gene was higher than found among Ashkenazi Jews in other
      countries, possibly because of ascertainment bias. A testing strategy with
      medical referral and individual reporting of carrier status may not be
      appropriate for all the community at risk and a modified strategy is necessary.

PMID- 7565237
TI  - Recognising drug and alcohol problems in patients referred to consultation
      liaison psychiatry.
AB  - OBJECTIVE: To study the extent of recognition by referring doctors of drug and
      alcohol problems in patients referred to consultation-liaison psychiatry for any
      reason, and the factors associated with non-recognition. DESIGN: Comparison of
      referring doctors' reasons for referral and psychiatrists' DSM-III-R diagnoses in
      2347 inpatients referred consecutively over three years, by means of the
      prospective MICROCARES clinical database used by the consultation-liaison
      psychiatry service of each hospital involved. SETTING: Four general teaching
      hospitals of Monash University. RESULTS: Psychiatrists considered a psychoactive
      substance use disorder diagnosis likely in 336 (14%) of the referred patients;
      referring doctors missed 188 (56%) of these, referring instead for "depression",
      "anxiety" and "suicide attempt evaluation". The factors correlating with this
      discordance included younger age, male sex, having a personality disorder
      diagnosed, and having attempted self-harm. CONCLUSIONS: The extent of the failure
      to identify drug and alcohol problems in patients in whom some psychological
      problem worthy of referral to psychiatry had been detected is symptomatic of the
      extent of this failure in medicine generally. Education and the use of screening
      procedures may lead to development of coherent drug and alcohol protocols in
      individual institutions.

PMID- 7565238
TI  - Chronic fatigue syndrome: current perspectives on evaluation and management.
AB  - OBJECTIVE: To describe clinical and laboratory guidelines for assessment and
      management of patients presenting with chronic fatigue syndrome (CFS). DATA
      SOURCES: Relevant international consensus diagnostic criteria and research
      literature on the epidemiology, pathophysiology, concurrent medical and
      psychological disturbance and clinical management of CFS. CONCLUSIONS: Medical
      and psychiatric morbidity should be carefully assessed and actively treated,
      while unnecessary laboratory investigations and extravagant treatment regimens
      should be avoided. No single infective agent has been demonstrated as the cause
      of CFS, and immunopathological hypotheses remain speculative. The aetiological
      role of psychological factors is debated, but they do predict prolonged illness.
      The rate of spontaneous recovery appears to be high. Effective clinical
      management requires a multidisciplinary approach, with consideration of the
      medical, psychological and social factors influencing recovery.

PMID- 7565239
TI  - Fundholding and rationing by general practitioners.

PMID- 7565240
TI  - Clinicians and management.

PMID- 7565241
TI  - Doctors in health care: can we determine the right numbers?

PMID- 7565242
TI  - Australian medical schools intake: threats to student numbers.

PMID- 7565243
TI  - Preoperative assessment and postoperative management of the elderly surgical
      patient.
AB  - The population undergoing surgery is aging and this trend will continue for many
      decades to come. Better anaesthetic and surgical techniques are lowering the risk
      benefit ratio for surgery, making it an increasingly attractive treatment option.
      Good preoperative assessment and postoperative management form an integral part
      of strategies to minimise morbidity and mortality while maximising hospital
      efficiency.

PMID- 7565244
TI  - The move towards evidence-based medicine.

PMID- 7565245
TI  - The move towards evidence-based medicine.

PMID- 7565246
TI  - Infection control practices.

PMID- 7565247
TI  - Isolation of HIV-1 from experimentally contaminated multidose local anaesthetic
      vials.

PMID- 7565248
TI  - Helicobacter pylori: how often are eradication therapies prescribed?

PMID- 7565249
TI  - Mesothelioma: is asbestos exposure the only cause?

PMID- 7565250
TI  - Lower back pain and sciatica: 25 years of tropical fruit treatment
      (chemonucleolysis)

PMID- 7565251
TI  - Free-flow waterbeds are potentially deadly to infants.

PMID- 7565252
TI  - Waiting times for non-urgent specialist appointments.

PMID- 7565253
TI  - Progress in clinical toxicology: from case reports to toxicoepidemiology.

PMID- 7565255
TI  - Strategies to avoid the risks of blood transfusion: are they widely applied in
      Australia?

PMID- 7565254
TI  - Geriatric medicine, a holistic specialty.

PMID- 7565256
TI  - Stroke: progress at last?

PMID- 7565257
TI  - Gastric emptying in acute overdose: a prospective randomised controlled trial.
AB  - OBJECTIVE: To test the hypothesis that administration of activated charcoal is as
      efficacious and safe as the combination regimen of gastric emptying plus charcoal
      in adults after acute oral overdose. DESIGN: Prospective randomised controlled
      trial, with subjects presenting on odd-numbered dates allocated to the emptied
      group (E), and those on even-numbered dates to the not-emptied group (NE).
      SETTING: Princess Alexandra Hospital, Brisbane (a tertiary referral hospital),
      which serves an adult urban community, between 4 January 1988 and 11 June 1990.
      SUBJECTS: Consecutive patients (13 years or older) who presented to the Emergency
      Department after ingesting an overdose of one or more compounds able to be
      adsorbed by activated charcoal. INTERVENTIONS: All patients received charcoal by
      the oral or nasogastric route. Those in the E group also had gastric emptying by
      ipecac-induced emesis or gastric lavage. OUTCOME MEASURES: Clinical course during
      the first six hours after treatment began, length of hospital stay,
      complications. RESULTS: 876 patients were eligible for the study. There were no
      significant differences between the E and NE groups in age and sex distribution,
      severity of the overdose or other characteristics, except the mean interval
      between presentation and administration of charcoal (91 min [SD, 52] for E group
      and 55 [SD, 41] for NE group; P = 0.0001). There were no significant differences
      between the E and NE groups in outcome, even when the groups were stratified for
      severity of the overdose or into subgroups that presented sooner or later than
      one hour after ingestion. CONCLUSIONS: Gastric emptying can be omitted from the
      treatment protocol for adults after acute oral overdose.

PMID- 7565258
TI  - Optimising collection of autologous blood. A pilot study of the use of
      recombinant human erythropoietin and parenteral iron.
AB  - OBJECTIVE: To optimise collection of sufficient autologous blood for elective
      surgery. METHODS: Prospective study of 40 patients referred for donation of
      autologous blood, who were booked for elective orthopaedic surgery in the period
      August 1992 - September 1994. Patients received recombinant erythropoietin (r
      EPO) to stimulate erythropoiesis, and sufficient iron by injection so that iron
      deficiency did not limit the bone marrow response to the r-EPO. RESULTS: Thirty
      eight of the 40 patients treated with this protocol stored an average of 3.7
      units each on a twice-weekly donation schedule. Only one patient required
      supplemental homologous blood (two units) in subsequent surgery. One patient
      developed persistent hypotension, and one a late reaction to parenteral iron
      (which was controlled with corticosteroids). There were no other adverse events.
      CONCLUSIONS: r-EPO in combination with parenteral iron is a safe and effective
      method of ensuring the collection of optimal amounts of autologous blood before
      surgery.

PMID- 7565259
TI  - Massive blood transfusion in a tertiary referral hospital. Clinical outcomes and
      haemostatic complications.
AB  - OBJECTIVE: To determine blood products used, clinical outcomes and frequency of
      haemostatic complications of massive blood transfusion. DESIGN AND SETTING:
      Retrospective review of the medical records of patients receiving more than 10
      units of blood in 24 hours at a tertiary referral hospital in 1993. PATIENTS:
      Forty-three patients fulfilled this criterion. The major reasons for massive
      transfusion were trauma (46%; 20 patients), gastrointestinal bleeding (21%; nine
      patients) and leaking abdominal aortic aneurysm (14%; six patients). MAIN OUTCOME
      MEASURES: Blood products used, platelet count ( < 50 x 10(9)/L in first 48 h),
      prothrombin time (PT) and activated partial thromboplastin time (APTT) (twice
      normal in first 48 h), microvascular bleeding, and survival. RESULTS: The 43
      patients used 824 units of packed cells 15.2% of the total used in 1993), 457
      units of fresh frozen plasma (FFP) (17.1% of the 1993 total) and 370 units of
      platelets (14.8% of the 1993 total). Overall, these patients consumed 16% of the
      total number of units of blood product used in 1993 for 1478 transfusion
      episodes. The overall survival rate was 60%. Severe coagulopathy occurred in 19
      patients (44%) (mortality rate, 74%), and 13 (31%) had severe thrombocytopenia (
      < 50 x 10(9)/L). There was no significant correlation between the severity of
      coagulopathy/thrombocytopenia and total units transfused, or between the age of
      the units of blood and development of coagulopathy or microvascular bleeding.
      CONCLUSIONS: Severe coagulopathy is common after massive transfusions. In the
      absence of clear correlation with the number of units transfused, "formula"
      replacement with plasma and platelets is unlikely to avoid the problem. Duration
      of tissue hypoperfusion and platelet consumption are likely to be more important
      than simple haemodilution of coagulation factors.

PMID- 7565260
TI  - Exaggerated hearing loss in noise induced hearing loss compensation claims in
      Victoria.
AB  - OBJECTIVE: To determine the incidence of exaggerated hearing loss in people
      claiming workers compensation for noise induced hearing loss, as well as the
      ability of a range of testers to detect this exaggeration. SUBJECTS: 333 people
      who claimed compensation for noise induced hearing loss between 13 September 1993
      and 31 July 1994 in Victoria and who had undergone two independent subjective
      hearing tests. METHOD: The hearing test results and referral decisions made by
      testers were examined in the light of the results of a single objective hearing
      test (cortical evoked response audiometry). RESULTS: The incidence of exaggerated
      hearing loss was 17.7%. Testers performing the first subjective hearing test
      detected only 2.2% of claimants who exaggerated. The audiologist performing the
      second subjective test detected 94.2% of claimants who exaggerated. CONCLUSIONS:
      The high incidence of exaggerated hearing loss and the large difference in
      ability to detect this exaggeration by the two groups of testers demonstrate the
      need for appropriate test procedures to be followed and a second hearing test to
      be reintroduced. Without accurate testing, there will be overpayment for noise
      induced hearing loss claims.

PMID- 7565261
TI  - Difficulties in clinical diagnosis of measles: proposal for modified clinical
      case definition.
AB  - OBJECTIVE: To examine the accuracy of clinical diagnosis of measles and to
      develop an improved measles clinical case definition. DESIGN: Case survey.
      SETTING: Eastern Sydney, December 1990 to August 1993. SUBJECTS: All cases of
      measles notified to the Eastern Sydney Public Health Unit without or before
      serological confirmation. OUTCOME MEASURES: Demographic and clinical details,
      measles- and rubella-specific IgM and measles complement fixation titres in acute
      and convalescent (when available) sera and epidemiological links with confirmed
      measles cases. RESULTS: Of 49 subjects reported and with complete follow-up, 24
      were confirmed with measles, four with rubella and 21 had no definite diagnosis.
      Clinical diagnosis of measles had a false positive rate of 51%. Subjects with
      confirmed measles were significantly more likely to have a cough (23/24) than
      those with no definite diagnosis (15/21; P = 0.03) and to be febrile on the day
      of rash onset (23/24 versus 10/21; P = 0.001). The Centers for Disease Control
      definition had a sensitivity of 92% but specificity of only 24%. A modified case
      definition of rash, cough and fever present at onset of rash had equal
      sensitivity but greater specificity (57%). CONCLUSIONS: As measles is no longer
      common in Australia, clinical diagnosis is unreliable. When a public health
      response is needed, cases should be confirmed by serological tests or, if not
      available, we propose use of our modified clinical case definition.

PMID- 7565262
TI  - New insights into osteoarthritis.
AB  - Not only has our understanding of cartilage structure, synthesis and breakdown
      increased over the last decade, but so have the possibilities for investigation
      and treatment of osteoarthritis. New strategies for investigation include
      ultrasound, magnetic resonance imaging, radionuclide scintigraphy, monitoring of
      biochemical markers for cartilage breakdown and miniarthroscopy. There is greater
      appreciation of the importance of exercise and analgesics in pain management, and
      drugs to retard cartilage breakdown are under development.

PMID- 7565263
TI  - Politics and health care: beyond the federal-state wrangle.

PMID- 7565264
TI  - Diabetes and hypertension. Australian Diabetes Society position statement.

PMID- 7565265
TI  - Nutritional disorders in the elderly.
AB  - Overnutrition and undernutrition can contribute to many common diseases or
      disorders in the elderly. Some conditions may take years to develop, while others
      can occur within weeks. Protein energy malnutrition may be the direct result of
      poor diet, or it may develop indirectly when other illnesses increase nutritional
      requirements beyond usual needs. One of the most easily recognised consequences
      of overnutrition is obesity, which is a risk factor for other diseases such as
      non-insulin-dependent diabetes mellitus, cardiovascular disease and hypertension.
      If nutritional disorders are identified and managed appropriately, the health of
      many elderly people can be significantly improved.

PMID- 7565266
TI  - Mammographic screening trials for women aged under 50.

PMID- 7565268
TI  - The effect of a common (viral) stress on plasma glutamine concentration.

PMID- 7565267
TI  - A positive hepatitis C enzyme immunoassay antibody test in a low risk population:
      what does it mean?

PMID- 7565269
TI  - Delayed notification of a large outbreak of diarrhoeal illness in a child care
      centre.

PMID- 7565270
TI  - Gestational diabetes: recent trends in Australia in screening and diagnosis.

PMID- 7565271
TI  - Children of parents with psychotic disorders.

PMID- 7565272
TI  - Respiratory depression associated with spinal narcotic anaesthesia.

PMID- 7565273
TI  - Prostate cancer: enthusiasm for screening.

PMID- 7565274
TI  - Paroxetine-induced SIADH.

PMID- 7565275
TI  - High and low roads to aboriginal health.

PMID- 7565276
TI  - Mesothelioma: is asbestos exposure the only cause?

PMID- 7565277
TI  - Proceedings of the 10th International Symposium Epidemiology in Occupational
      Health. Como, Italy, 20-24 September 1994.

PMID- 7565278
TI  - Genetic susceptibility in the occupational setting: introduction to the workshop.

PMID- 7565280
TI  - Markers of susceptibility and environmental cancer risk: experiences in Italy.

PMID- 7565279
TI  - Genetic susceptibility and occupational cancer.
AB  - This review describes statistical models for the biological interaction of
      susceptibility genes and environmental exposures, as observed in epidemiologic
      studies. The importance of metabolic transformation of industrial carcinogens and
      the potential role of genetic polymorphisms in metabolic enzyme activity are
      outlined. Several genetic polymorphisms have been associated with cancer risk,
      but the link with the relevant exposures has only infrequently been specified.
      For example, studies show that slow N-acetylation increased bladder cancer risk
      among workers exposed to some arylamines, as found among dye workers in England,
      but that this effect does not hold for benzidine exposure. This link of a genetic
      susceptibility factor with cancer risk due to some aromatic amines, but not to
      others, illustrated the specific nature of metabolic environment/gene
      interactions. Epidemiologic studies to investigate the role of genetic
      susceptibility in cancer development promise to further the identification of
      human carcinogens by focusing on susceptible individuals and, in turn, to enhance
      understanding of human cancer by relating cancer risk in populations to
      underlying biologic processes. Occupational studies are key to this effort.

PMID- 7565281
TI  - Use of case-control studies in the general population and in occupational cohorts
      to study genetic susceptibility and cancer risk.

PMID- 7565282
TI  - A genetic marker for chronic beryllium disease.

PMID- 7565284
TI  - Occupational exposure to carcinogens and cancer occurrence in Europe.

PMID- 7565283
TI  - ALA-D genotype is not associated with HT or HB levels among workers exposed to
      low levels of lead.

PMID- 7565285
TI  - Occupational cancer in central Europe.

PMID- 7565286
TI  - Occupational cancer in the Mediterranean Region.

PMID- 7565287
TI  - Occupational cancer problems in the European part of the Commonwealth of
      Independent States.

PMID- 7565289
TI  - Occupational cancer in Europe as it relates to the chemical industry in the
      1990's.

PMID- 7565288
TI  - Identifying associations between cancer and occupation in women in Europe. The
      role of routinely collected national data.

PMID- 7565290
TI  - Asbestos and cancer.

PMID- 7565291
TI  - Participatory approaches in occupational health research: a review.

PMID- 7565292
TI  - Principles of toxicology of importance in epidemiology.

PMID- 7565293
TI  - Biomarkers.

PMID- 7565294
TI  - Babies, bread, and basic science: input output relationships do not generalize.

PMID- 7565295
TI  - Organic solvent exposure, mood disorders, and cancer risk. An hypothesis.

PMID- 7565296
TI  - Silica, silicosis, and risk of tuberculosis and lung cancer.

PMID- 7565298
TI  - Over-the-counter H2-receptor antagonists for heartburn.

PMID- 7565297
TI  - Drugs for AIDS and associated infections.

PMID- 7565299
TI  - Sevoflurane for general anesthesia.

PMID- 7565300
TI  - Nalmefene--a long-acting injectable opioid antagonist.

PMID- 7565301
TI  - The effects of the atomic bombings of Hiroshima and Nagasaki.

PMID- 7565303
TI  - SIOP Working Committee on Psychosocial Issues in Pediatric Oncology: guidelines
      for school/education.

PMID- 7565302
TI  - Hiroshima and Nagasaki: the beginning of the nuclear age.

PMID- 7565304
TI  - p53 gene mutations in pediatric brain tumors.
AB  - We investigated the frequency of p53 mutations in 47 pediatric brain tumors of
      various histologic subtypes that were collected over a period of 5 years. The
      specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade
      astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed
      glial tumor, eight ependymomas, one choroid plexus carcinoma, and one
      gangliocytoma/ganglioneuroma. Mutations were identified by single strand
      conformation polymorphism analysis of exons 4-8 and verified by sequencing.
      Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade
      astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC
      to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A
      second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with
      loss of the wild-type allele, but normal tissue was not available for comparison.
      In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic
      CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in
      other histologic subtypes and in two cases with multiple primary cancers. These
      data are consistent with earlier findings that p53 mutations are rare in PNETs,
      which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations
      in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in
      pediatric low grade astrocytomas suggests not only histological differences, but
      also a different molecular pathogenesis in adult and pediatric patients.

PMID- 7565305
TI  - DNA index and %S-phase cells determined in acute lymphoblastic leukemia of
      children: a report from studies ALL V, ALL VI, and ALL VII (1979-1991) of the
      Dutch Childhood Leukemia Study Group and The Netherlands Workgroup on Cancer
      Genetics and Cytogenetics.
AB  - DNA per cell content was routinely recorded by single-parameter flow cytometry in
      leukemic blasts from 473 children with acute lymphoblastic leukemia (ALL),
      enrolled in national studies ALL V, VI, and VII (1979-1991) of the Dutch
      Childhood Leukemia Study Group. The parameters bonemarrow %S-value and DNA Index
      were compared with clinical features, with chromosome number based on cytogenetic
      analyses and with treatment results in study ALL VI. %S-values, ranging between 1
      and 36%, were unrelated to initial white blood cell count, immunophenotype, and
      DNA index but were lowest in blasts with L1 morphology. In study ALL VI (non-high
      risk), the survival of patients with < or = 6% S-phase cells was superior to that
      of patients with %S-values of > 6 (P = 0.030). Hyperdiploidy, defined by a DNA
      index > or = 1.16, was compared to the cytogenetic hyperdiploid classification of
      n > 50. Initially there were 25 discrepancies in 189 samples jointly analysed by
      flow cytometry and cytogenetics. After review only five discrepancies remained
      unresolved. Hyperdiploidy, independent of the method used, was found to be
      unrelated to blast morphology and %S-phase cells but closely associated with c
      ALL and was absent in T-ALL. In study ALL VI, event-free survival at 8 years of
      hyperdiploid patients was 90.6% but was not significantly different from non
      hyperdiploid patients (EFS = 82.1%; P = 0.08). Routine DNA flow cytometry
      appeared a valuable adjunct to cytogenetic analyses and allowed the
      identification of a large subset of non-high-risk ALL patients in study ALL VI
      with a DNA index > or = 1.16 or %S-value of < or = 6.0 with highest survival
      probability.

PMID- 7565306
TI  - Is there a gender difference in red blood cell thiopurine methyltransferase
      activity in healthy children?
AB  - We have examined red blood cell (RBC) thiopurine methyltransferase (TPMT)
      activity in a healthy population sample of Norwegian children, age 1-10 years.
      Boys had mean RBC TPMT activity of 11.1 +/- 2.0 U (n = 87) vs. 10.6 +/- 2.2 U (n
      = 71) in girls, the difference was not significant (P = 0.3). Age was negatively
      correlated to RBC TPMT activity (rs = -0.2, P = 0.01). As boys with acute
      lymphoblastic leukemia (ALL) tolerate more 6-mercaptopurine (6-MP) than girls and
      have a higher risk of relapse, we have searched for pharmacokinetic causes of
      these gender differences. The gender difference in 6-MP tolerance and clinical
      outcome in children with ALL cannot be explained by the minor and nonsignificant
      higher RBC TPMT activity in boys compared to girls.

PMID- 7565307
TI  - Survival and quality of life of paediatric intracranial germ cell tumour patients
      treated at the Christie Hospital, 1972-1993.
AB  - From 1972 to 1993, 25 patients under 16 years old were treated at the Christie
      Hospital for intracranial germ cell tumours (ICGCTs). A retrospective analysis of
      the case notes was undertaken. The cases comprised 10 germinomas, nine non
      germinomatous germ cell tumours (NGGCTs), and six cases with no histology. Ten
      patients had either complete or incomplete removal of the tumour. All patients
      received radiotherapy (20 patients received craniospinal irradiation [CSI]).
      Thirteen patients received chemotherapy at presentation (six platinum-based). All
      marker-negative pure germinomas treated with CSI survived. The actuarial 5-year
      survival for NGGCTs was 44%. Although CSI resulted in spine shortening, the
      overall effect on growth was not marked and the neuropsychologic sequelae were
      minimal with good overall functional results.

PMID- 7565308
TI  - Tropisetron in the prevention of nausea and vomiting in 131 children receiving
      cytotoxic chemotherapy.
AB  - Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a selective
      antagonist of the serotonin receptor (5-HT3) dosed once-daily at 0.2 mg/kg (with
      a maximum of 5 mg daily), was evaluated in the prevention of chemotherapy-induced
      nausea and vomiting in 131 children with a median age of 5 years (age 10 weeks to
      21 years). Acute lymphocytic leukemia was the most common malignancy (49%). Most
      children (82%) had received cytotoxic chemotherapy before enrollment. Patients
      received tropisetron during one or more courses of chemotherapy (455 courses in
      total). Tropisetron was administered slowly intravenously as a single dose before
      the start of chemotherapy on day 1 and intravenously or by mouth the subsequent
      days as a single daily dose (median treatment duration: 5 days). Response to
      tropisetron per 24 hour period on the first 5 days of each chemotherapy course
      was graded as complete (absence of both nausea and vomiting), partial (one to
      four vomits and/or less than 5 hours of nausea), or failure. Overall complete
      response on day 1 was observed in 305 out of 455 chemotherapy courses (67%). The
      patients receiving intravenous chemotherapy (N = 92) had a 70% complete response
      rate and a 26% partial response rate on day 1, both for course 1 and course 2.
      The percentage of complete responders increased the subsequent days of the
      course. Emesis after day 1 was observed primarily during courses with the most
      emetogenic chemotherapy. No side-effects of tropisetron other than a single case
      of diarrhoea were documented in this study.

PMID- 7565309
TI  - High-dose-rate brachytherapy in childhood sarcomas: a local control strategy
      preserving bone growth and function.
AB  - The administration of external beam radiation therapy (EBRT) has been an integral
      part of the successful treatment of childhood sarcomas. However, EBRT has severe
      late morbidity in the developing child. In an attempt to deliver adequate
      tumoricidal radiation while preserving bone growth and organ function, 13
      children with diverse sarcomas were treated with high dose rate brachytherapy
      (HDR). Seven patients had rhabdomyosarcoma and six patients had other soft tissue
      sarcoma variants. All patients were treated with disease-appropriate
      chemotherapy, usually according to the intergroup Rhabdomyosarcoma Study. Eleven
      patients received fractionated 36 Gy HDR alone at a mean of 3.5 months from
      diagnosis. Two patients received 10-12.5 Gy intraoperative HDR brachytherapy and
      additional 27 Gy EBRT. Nine of 11 patients in first remission have had no
      recurrences. One died of recurrent pulmonary metastases. The other patient that
      did recur is disease-free 21 months post-recurrence. Two additional patients were
      treated with HDR after tumor recurrence. One patient with recurrent Ewing's
      sarcoma, relapsed and died. The second is disease free 3 months after autologous
      bone marrow transplant. Grade 1 morbidity occurred in 46%, Grade 2 in 15%, and
      Grade 3 in 8% of the children, while relatively good bone and organ growth was
      maintained. The combination of conservative surgery, chemotherapy, and HDR offers
      the potential for disease control in young children while preserving bone growth
      and organ function.

PMID- 7565310
TI  - Plain radiography for diagnosis of gastrointestinal perforation in immune
      compromised children--is it enough?
AB  - Gastrointestinal perforation is a surgical emergency in the pediatric patient and
      any delay in diagnosis might be hazardous. In immunocompromised children, the
      clinical signs of perforation may be blunted. We describe a child with acute
      lymphoblastic leukemia (ALL) and a perforated appendix and ileum in whom
      computerized tomography (CT) revealed extraluminal air that was not initially
      identified on plain abdominal film. Our case demonstrates the importance of early
      abdominal CT and ultrasound examination in detecting these potentially lethal
      complications.

PMID- 7565311
TI  - Acute renal failure in high dose carboplatin chemotherapy.
AB  - Carboplatin has been reported to cause acute renal failure when administered in
      high doses to adult patients. We report a 4 1/2-year-old girl who was treated
      with high-dose carboplatin for metastatic parameningeal embryonal
      rhabdomyosarcoma. Acute renal failure developed followed by a slow partial
      recovery of renal function. Possible contributing factors are discussed.

PMID- 7565312
TI  - Simultaneous choriocarcinoma in mother and newborn infant.
AB  - A male infant, born following an uncomplicated pregnancy, was severely anaemic at
      birth following significant foeto-maternal haemorrhage. At three weeks of age a
      tumour was found in the liver with evidence of metastatic disease in the lungs.
      The infant died before treatment could be started. Postmortem revealed
      choriocarcinoma which led to subsequent diagnosis in the mother who also had
      pulmonary metastases. The mother has been successfully treated. The case is
      described in detail and followed by a discussion and a literature review of
      reported cases of simultaneous choriocarcinoma in infant and mother.

PMID- 7565313
TI  - Pleuro-pulmonary blastoma: a case report and review of the literature.
AB  - Pleuro-pulmonary blastoma is a rare malignant lung tumor in children and distinct
      from ordinary pulmonary blastoma of adulthood. Combination chemotherapy plays an
      important role in the treatment of this tumor, but so far no attempt of high dose
      chemotherapy with subsequent bone marrow or blood stem cell transplantation has
      been published. The case is reported of a 2-year-old boy with pleuro-pulmonary
      blastoma who achieved partial remission with conventional chemotherapy and
      surgery. Subsequent administration of high dose melphalan, etoposide, and
      carboplatin, followed by autologous blood stem cell transplantation resulted in a
      3-month disease-free interval but did not prevent eventual local recurrence,
      leading to death within a few weeks. Clinical presentation, pathology,
      management, and prognosis are discussed and the literature reviewed.

PMID- 7565314
TI  - Chemotherapy-induced veno-occlusive disease of the liver.

PMID- 7565315
TI  - [Relation between preclinical and clinical studies--status and perspectives].

PMID- 7565316
TI  - [Vascular characteristics of the human subfornical organ].
AB  - The aim of the study regarding adult brains is to determine the sources of
      vascularization, vascular area, the size and density of the capillary network of
      the human subfornical organ. The examined brain blood vessels under filled with a
      mixture of Indian ink and gelatin. The serial paraffin sections of 50 and 200
      microns were cleared after Spalteholz. In the vascularization of this
      neuroendocrine structure of the diencephalon, two arterial stems take part with
      their branches: a. cerebri anterior and a. choroidea posterior. In order to
      quantify the density of the capillary network, the authors used the standard
      stereologic parameters volume density, surface density and mean radius of blood
      vessels. By the comparative test of obtained mean values of males and females no
      statistically significant differences pertaining to sex and in respect to the
      size and density of capillary network in subfornical organ were confirmed. While
      the precise functions of the human subfornical organ have yet to be fully
      elucidated, the similarity in organization of this region to the vascular organ
      of the lamina terminalis, has led several authors to suggest that the subfornical
      organ is a site of receptors which are stimulated by circulating angiotensin II
      to induce water drinking and vasopressin secretion.

PMID- 7565317
TI  - [Possibilities of interventional ultrasonography in the differential diagnosis of
      pancreatic malignancy].
AB  - Pancreatic carcinoma is one of the most aggressive visceral malignancies with
      lethal ending in 99% of cases. Although diagnostic methods make a great progress,
      the world epidemiologists consider this disease to be increasing. The main reason
      for this is probably the problem of making early diagnosis. Various diagnostic
      techniques including ultrasonography often make no difference between benign and
      malignant changes. The aim of this paper is to consider values of pancreatic
      functions under the control of ultrasound in a group of patients. The examination
      included patients with evident pancreatic changes. By cytopathologic analysis of
      the gathered material clear diagnosis was made. In most cases malignancy was
      established. The aim of diagnostic examination is to make diagnosis as early as
      possible, using minimal number of tests which should be the least invasive and
      traumatic for patients. As a diagnostic method ultrasonography is fast and simple
      which provides better chances for patients with pancreatic carcinoma.

PMID- 7565318
TI  - [Effects of ethanol on thyroid gland development].
AB  - Maternal ingestion of alcohol appears to cause a pattern of congenital anomalies
      with pre- and postnatal growth in the offspring. In order to study the possible
      implication of thyroid function in the effect of exposure to alcohol, we have
      studied structural alterations of this gland during early postnatal period (0-20
      days) of the rats from alcohol-fed mother, which were given 15% ethanol as the
      only drinking solution daily one month before and during pregnancy and lactation.
      The results of the light-microscopic and stereological analysis clearly show that
      maternal ingestion of ethanol results in the stimulation off the thyroid gland of
      their pups. This was the most prominent in 20-day-old rats, what is substantiated
      by the much more irregular apical surface of the follicular cells, appearance
      numerous colloid droplets, significant increase both the volume density of
      follicular epithelium (p < 0.05) and interfollicular tissue (p < 0.001) and
      significant reduction in volume density of colloid (p < 0.001). These results
      suggest that maternal ethanol exposure disturbs the normal structure of the
      thyroid gland of their offspring what may, at least partly, mediate to alcohol
      induced detrimental effect on growth and development in the fetus and neonate.

PMID- 7565320
TI  - [Blood of patients with acute leukemia increases the leukocyte count in the
      peripheral blood of mice].
AB  - Serum of 23 patients suffering from acute myeloid leukemia were given to groups
      of six mice (s.c. 0.6 ml); 3 and 5 days later the total number of leucocytes,
      granulocytes and lymphocytes was determined in the peripheral blood of mice.
      Serums of all patients caused significant increase of leucocytes in mice 3 and/or
      5 days after the serum's application. In most cases the increase was caused by
      increased number of granulocytes and lymphocytes, and in 6 cases only by increase
      of granulocytes or only lymphocytes. This increase can also be thought of as a
      stimulation of leukocytopoiesis by increased concentration of hematopoetic growth
      factors in blood of those suffering from acute leukemia.

PMID- 7565319
TI  - [The effect of contaminants on characteristics of 99mTC radiopharmaceuticals].
AB  - The influence of 99Tc, oxygen and cupric ions on labeling yield of eight
      radiopharmaceuticals was examined. The results obtained for commercial and
      experimental preparations were compared. The latter were formulated so that the
      content of 99Tc was 4 times, hydrogen peroxide 5 times and copper 50 times higher
      than in commercial preparations. It was found that these impurities did not
      affect labeling of 99mTc(Sn)tetracyclin, 99mTc(Sn)dimercaptosuccinate and
      99mTc(Sn)diethylida. Long-living 99Tc did not affect any preparations. Oxygen
      influenced in lesser extent 99mTc(Sn) DTPA, 99mTc(Sn)pyrophosphate and 99Tc(Sn)
      dicarboxy-propane diphosphonate but strongly 99mTc(Sn) phytate 99mTc(Sn)methylene
      diphosphonate. Copper influenced only 99mTc(Sn)-methylene diphosphonate.
      Therefore this preparation was examined in broader range of copper
      concentrations. According to the results of radiochemical and biodistribution
      analyses it was concluded that under the experimental conditions the effect of
      oxygen and copper resulted in an increased content of free 99mTc-pertechnetate in
      the examined preparations.

PMID- 7565321
TI  - [Determination of lipoprotein Lp(a) in clinical practice: personal experience].
AB  - The paper presents up-to-date knowledge on structure, origin, metabolic ways and
      physiologic role of lipoprotein Lp(a). Apart from discussing analytic actions,
      plasmatic distribution and conjunction with atherosclerosis, results of our own
      investigations which took several years performed in about 5000 patients are
      being reported as well as directives for rational diagnostic and therapeutic
      approaches.

PMID- 7565322
TI  - [Psychology of severe somatic diseases].
AB  - This paper deals with description of all possible stages of complex psychological
      and especially emotional occurrences in patients with serious somatic diseases.
      It is pointed to the necessity of considerate treatment of these patients
      appreciating their personal characteristics. Knowledge on existence of emotional
      reactions regarding serious somatic diseases pointed to the necessity of
      psychotherapeutic as well as pharmacotherapeutic care of these patients.

PMID- 7565323
TI  - [Malignant tumors of the oropharynx].
AB  - Data on 31 patient suffering from malignant tumors of oropharynx were analyzed
      during a 5 year period at the Clinic for otorhinolaryngologic diseases.
      Oropharynx carcinoma was pathohistologically diagnosed in all patients. It is an
      illness which occurs in older people, in 87% in patients older than 60 years of
      age, and mostly in males (9:1). 77.4% were smokers, 83.8% consumed alcohol while
      38.7% were treated for alcoholism. The first and most frequent symptoms are
      odynophagia (58.1%) and dysphagia (38.7%). Metastases of lymph nodes of the neck
      were present in 64.5% of the sick at the time when sickness was diagnosed and all
      were ipsilateral. 25.8% of patients were surgically treated and 6 of them were
      also treated by radiation. 54.8% of patients were primarily treated with
      telecobalt therapy. Three year survival in 3 patients points to extremely
      negative localization of the malignant process with a bad course and outcome.

PMID- 7565324
TI  - [Evaluation of long-term prognosis in patients with whiplash syndrome].
AB  - We reviewed 50 patients who sustained whiplash injuries of the neck. The mean
      time of the follow-up was 3 years. Only 16% of observed cases recovered
      completely. Residual symptoms were severe in 38%. Pain in the neck, headache and
      paraesthesia were the commonest complaints. Older patients and patients with
      significantly restricted movements of the neck, sharp local kyphotic deformity,
      chronic instability and neurologic involvement had a worse prognosis.

PMID- 7565325
TI  - [The effect of noise and vibration on the cardiovascular system in exposed
      workers and possibilities of preventing their harmful effects].
AB  - We examined the state of blood pressure, peripheral arterial circulation and
      changes of polycardiogram before and after three hour work of 160 workers
      professionally exposed to noise and vibrations. They were divided into two sub
      groups regarding physical recreational activity (walking, swimming or running),
      with the average load level from 60% to 80% of maximal oxygen consumption. 85
      workers made up the control group. They were not exposed to noise and vibrations
      at work. The gathered results show that the prevalence of the arterial
      hypertension and obliterating endarteritis is statistically significantly higher
      in the group of workers exposed to noise and vibrations and that these
      professional damages cause important hemodynamic changes of cardiovascular
      system, but also that permanent physical recreational activity (swimming, running
      or walking) can prevent such effects.

PMID- 7565327
TI  - [Therapy of salmonella gastroenterocolitis].
AB  - At the Clinic for infectious and dermatovenerologic diseases in Novi Sad a
      prospective randomized, simple, blind investigation of differently organized
      treatments of salmonellal gastroenterocolitis (symptomatic therapies, ampicillin,
      co-trimoxazole and ciprofloxacine) was carried out. It was established that there
      is no statistically significant difference in the length of febrile states in any
      of the compared therapeutic groups. However, ciprofloxacine significantly
      shortens diarrhea and excretion of germs comparing with other therapeutic
      treatments.

PMID- 7565326
TI  - [Reference values of anthropometry parameters in school children and youths in
      Subotica].
AB  - Anthropometric measurements are most often used in order to evaluate the state of
      nourishment and gain insight into body growth and development of children and
      young people. The use of different criteria in everyday practical work causes
      very diversified results and at the same time presents a problem in early
      detection of certain disorders of growth, development and state of nourishment
      and in undertaking adequate dietetic and therapeutic treatments. In Subotica
      18864 persons from 8-19 years of age were examined by transverse anthropometric
      measurements of height and weight. By statistical processing of results mean
      values, medians and percentiles of body height, body mass and the body mass
      index, BMI (kg/m2) were established. These reference values present a base for
      producing nomogram of growth, development and state of nourishment in children
      and young people in our area which could be applied in everyday work at clinics.

PMID- 7565328
TI  - [Successful treatment of acquired F:VIII C inhibitor after delivery using
      plasmapheresis and high doses of immunoglobulins].
AB  - Three months after delivery a patient 34 years of age was admitted to the Clinic
      of haematology in Novi Sad because of sudden massive bleeding from the left
      ankle, left lower leg as well as for having small haematomas visible at forearms.
      Examining the mechanism of haemostasis, a diagnosis was made: acquired inhibitor
      VIII:C coagulation factor. Concentrate of VIII coagulation factor was used in
      treatment, as well as plasmaphaeresis, high doses of immunoglobulins and
      immunosuppressive drugs: prednisone and azathioprime. The result was a very quick
      recovery of the clinical state with loss of inhibitor to VIII: C coagulation
      factor. Three years after the treatment the patient has no difficulties and no
      antibodies to VIII:C coagulation factor.

PMID- 7565329
TI  - [Whipple's disease. Case report].
AB  - This is a case report on a 42 years old patient suffering from Whipple's disease.
      The patient had characteristic symptoms: high temperature, frequent bowel
      movement, melanoderma, arthralgia and enlarged lymph nodes. After detailed
      clinical researches, x-ray and endoscopic examination, bacteriology examination
      of faeces, absorptional tests, the diagnosis was made thanks to pathohistologic
      analysis of biopsy samples of the small intestine by light and electron
      microscopy. The differential diagnostic similarity with AIDS, especially at the
      early phase of the illness, required excluding HTLV III. We examined the
      aetiophathogenesis of the illness and discussed the clinical and laboratory
      presentation of the patient considering contemporary ideas regarding this
      disease.

PMID- 7565330
TI  - [150th anniversary of the birth of Vladan Dordevic 1844-1930].

PMID- 7565331
TI  - [A world without polio by the year 2000].

PMID- 7565332
TI  - [Relation between pyloric dysmotility and serum levels of gastrin, somatostatin
      and vasoactive intestinal polypeptide in patients with non-insulin dependent
      diabetes mellitus].
AB  - Serum levels of gastrin, somatostatin and vasoactive intestinal polypeptide were
      evaluated in 105 noninsulin dependent diabetics (25 of them had a pyloric
      dysfunction). The serum levels were determined by RIA and blood was taken before
      and after the test meal. The basal gastrin level was significantly higher in
      patients with the pyloric dysfunction (p < 0.001). 45 minutes later the serum
      levels of vasoactive intestinal polypeptide and somatostatin were significantly
      higher in diabetics with the pyloric dysfunction (p < 0.001). The serum levels of
      gastrin, somatostatin and vasoactive intestinal polypeptide were impaired in
      diabetics with the pyloric dysfunction and might be associated with its
      pathogenesis.

PMID- 7565333
TI  - [Morphologic characteristics of the gyrus cinguli vascular network].
AB  - Vascular network of gyrus cinguli has been examined in adult brains. This
      vascular network is extended in the form of a cone from lower to upper lip of
      Sulcus corporis calosi. The blood vessels in the area of lower lip and bottom of
      the Sulcus corporis calosi are oriented obliquely, almost parallel to cerebral
      cortex surface, while in the area of upper lip of sulcus are oriented
      perpendicularly to the cerebral cortex surface. Arteries in this area have few
      recurrent branches, while fountain shaped arteries are found infrequently.
      Shorter spiral arteries are found, too. Longer veins predominates in this area
      (V4 and V5). Drainage territories of certain veins are larger than irrigation
      territories of the appropriate arteries.

PMID- 7565334
TI  - [Anti-proteinuria effects of nonsteroidal anti-inflammatory drugs in patients
      with nephrotic syndrome: an illusion or a read improvement?].
AB  - In order to examine the antiproteinuric effect of non-steroidal antiinflammatory
      drugs in patients with nephrotic syndrome, we performed a parallel determination
      of the daily proteinuria, strength of glomerular filtration and of the effective
      renal plasmatic flow in basal conditions and after a 7 day ibuprofen therapy at a
      daily dose of 1200mg (3 x 400mg) in a group of 12 patients with idiopathic
      glomerulonephritis. In all patients ibuprofen therapy induced a significant
      decrease of the existing proteinuria, but this decrease was accompanied by the
      decrease of clearance rate of 99mTc-DTPA and 131J-hipuran clearance, that is by
      decrease of strength of glomerular filtration (averagely 24.29%) and effective
      renal plasmatic flow (averagely 18.74%). It can be concluded that the decrease of
      proteinuria in patients with nephrotic syndrome after ibuprofen therapy (as well
      as other non-steroidal antiinflammatory drugs) is primarily the result of
      worsening of hemodynamic conditions in the kidney, that it is caused by the
      reduction of the renal blood flow and by the strength of glomerular filtration in
      conditions of cycloxygenetic activity inhibition in the kidney.

PMID- 7565335
TI  - [Changes in prolactin plasma levels in relation to menopausal status in primary
      breast carcinoma].
AB  - Prolactin plasma level was measured in healthy controls, 110 benign breast
      lesions and 17 primary breast cancers, and results were correlated in regard to
      pre and postmenopausal groups of female subjects. Prolactin concentration in
      healthy controls and benign breast lesions was higher postmenopausally, and in
      breast cancer premenopausally, with the absence of statistically significant
      difference. At the same time menopausal cases of primary breast cancer had a
      significantly higher prolactin level than the same subgroup of healthy controls
      (222.7 +/- 16.7 vs. 91.8 +/- 11.6; p < 0.05). It can be concluded that the
      changes of prolactin basal level had a different consequence in female patients
      with primary breast cancer in correlation with benign breast lesions and healthy
      controls. Consequently, in future investigations of unclear roles of prolactin in
      mammary tumourogenesis a possible relation among various hormonal factors,
      premenopause and primary breast cancer should be discussed.

PMID- 7565337
TI  - [Mastocytes in the diagnosis of chronic rhinitis].
AB  - In order to detect the allergic etiology of the disease, we looked for mastocytes
      in 18 patients with chronic vasomotor rhinitis 5 of these patients also had nasal
      polyposis. Mastocytes were found neither in the nasal smear of any patients nor
      in the scarification smear nor in the nasal smear of any patients nor in the
      scarification smear nor in the smear of the biopsy material, but they were found
      in the deeper layers of the nasal mucosa. They were regularly in the stroma and
      always with lymphoplasm-histocyte infiltrations. Prick-tests were negative in 13
      out of 18 tested patients. By a follow up of 13 patients with chronic rhinitis it
      was established that findings of 7 patients were in correlation. In 3 patients
      skin tests, were positive and mastocytes present, while in 4 patients both of
      these parameters were negative. In 2 patients skin tests were positive and
      mastocytes negative, while in the other 4 patients skin tests were negative with
      a positive mastocyte finding, which points to allergy. Finally, in patients with
      nasal polyposis skin tests were negative with mastocytes positive in 4 out of 5
      patients. The gathered results reveal that mastocytes were found in 11 out of 18
      examined patients, that is in 61%, which is an encouraging fact and demands a
      further follow up and checking in a larger number of cases.

PMID- 7565336
TI  - [Use of urinary enzymes in diagnostic follow-up in kidney transplantation].
AB  - This is a short review of the problem considering follow up of patients with
      kidney transplants using urinary enzymes. Among various urinary enzymes which are
      followed up in these patients, enzymes of proximal tubules were assumed to be the
      most important. By analysis of numerous authors we came to the conclusion that
      urinary enzymes may be important in such pathology, but only under certain
      conditions.

PMID- 7565338
TI  - [Mammographic structure of breast parenchyma and the manifestations of breast
      cancer].
AB  - The occurrence of breast carcinoma in regard to mammographic parenchyma samples
      applying the technique of Wolfe was analyzed. In the examined group of patients
      (n = 105) after clinical and mammographic examination mastectomy was performed
      with evacuation of axillary tissue. The malignancy was confirmed
      pathohistologically as well as the degree of spreading. The control group
      consisted of (n = 105) patients of the same age in whom at the time of
      examination and 6 months later malignancy was not confirmed. P-2 was more
      frequent in the group of the sick, while N-1 sample (X2 = 17.15, p < 0.01) was
      rarer. In patients older than 50 years of age Dy sample (x2 = 11.95, p < 0.01)
      was also more frequent. The difference can be explained by the fact that P-2 and
      Dy mammographic samples represent the picture of dysplastically changed breast
      tissue and depending on the presence of histologic elements of proliferation and
      cell atypias point to an increased risk of cancer. Consequently the samples are
      divided into "highly risky" (P-2 and Dy) and "of low risk" (N-1 and P-1). Women
      with mammographic parenchymal samples of a higher risk together with other risk
      factors should be frequently controlled.

PMID- 7565339
TI  - [Prediction of progression of suppurative meningitis based on clinical
      characteristics and cerebrospinal fluid findings at the onset of the disease].
AB  - Some factors (sex, age, the way of onset, previous antibiotic therapy, instant of
      hospitalization in relation to the appearance of initial symptoms) associated
      with the course of suppurative meningitis prior to the hospitalization have been
      analyzed and a trial has been made to locate them in the prognosis of the disease
      progression. At the Clinic of Infective Diseases in Novi Sad during 10 years
      (1977 to 1987, except 1983) 162 patients with a diagnosed purulent meningitis had
      been treated. The patients were classified into two groups: a group of 62
      patients with complications and a group of 100 patients with an expected
      progression of the disease. Statistical data were analyzed using the x2 test and
      t test. In the period considered in this investigation the sickness passed with
      complications in 38.24% cases, 32.10% of them being of neurological nature, while
      6.14% of complications appeared in other organs and systems. The statistical
      analysis shows that sex, age, the way of onset (data from history of the
      disease), previous antibiotic therapy, time of hospitalization in relation to
      appearance of initial symptoms, can not be used as reliable parameters in
      predicting the further course of suppurative meningitis. Complications have been
      registered in patients having more than 2.16g/l proteins and less than 1.12mmol/l
      sugar in the liquor at the beginning of the disease. These values can be used as
      a reference for predicting the further course of the disease.

PMID- 7565340
TI  - [Hemorrhagic stress lesions in the gastroduodenal mucosa. Incidence and therapy].
AB  - We have observed 428 patients with hemorrhages of the upper gastrointestinal
      tract; 7% of patients with stress lesions of the gastroduodenal mucosa being the
      cause of hemorrhages (4.9% were erosional stress hemorrhages and 2.1% were stress
      ulcera). Surgery is the most common cause of stress hemorrhages of the stomach
      and duodenum. They occur during the first 5 days after the surgery, whereas
      70.59% (n = 12) occur during the first 72 hours. The localization of erosional
      hemorrhages of the stomach mucosa is mostly diffuse and that is why they are
      numerous (78.6% of the third degree) and hemorrhages are mostly heavy (the case
      with stress hemorrhages). Chronic peptic ulcera, especially duodenal (62.5%
      duodenal ulcera and 37.5% stomach ulcera) present an expressed risk factor for
      the occurrence of hemorrhagic erosions under the influence of the stress factor.
      The most common localization of the stress hemorrhagic ulcus is duodenum (66.7%)
      which is a potential danger for occurrence of the heaviest arterial hemorrhages.
      After major surgeries and during postoperative periods patients must be
      preventively protected by "antiulcus therapy" (especially patients with ulcera).

PMID- 7565342
TI  - [Ultrasonic characteristics of kidneys in chronic kidney insufficiency].
AB  - Ultrasound examination of kidneys obtains various information on the state of
      kidneys which may point to the function itself: the size of kidneys, their shape,
      the state of edges and cortex, their relation with the surrounding tissues and
      organs, parenchymal structure and width, presence of delay in the conveying
      system, nature of obstacles as well as their localization. Excretory, intravenous
      urography is mostly impossible to perform in patients with renal insufficiency so
      that is why we mainly practice ultrasound checkups and laboratory analyses in
      surveying the state of kidneys. This is a report on a sample of patients with
      chronic renal insufficiency who were on chronic hemodialyses. The most common
      cause of renal failure are the following: endemic nephropathy 29.70%, various
      inflammatory states 34.24% and congenital anomalies 6.6%.

PMID- 7565341
TI  - [Chronic urticaria from the aspect of autoimmune diseases].
AB  - At some time in their lives one in a five persons is affected by urticaria and/or
      angioedema. The cause of urticaria may never be found in up to one quarter of
      patients with acute urticaria and in up to 90-95% with chronic urticaria. In this
      study we present results of our compounded approach (clinical follow up,
      laboratory findings, allergological testing) to patients with chronic urticaria
      and autoimmune diseases that progressed into chronic urticaria or started before
      the onset of the chronic urticaria. Our first case was a 56 year old woman with a
      10 month history of chronic urticaria, angioedema and chronic gastritis before
      the diagnoses of insulin dependent Diabetes mellitus and Hypothyreoidismus
      primarius were established. Allergological testing reveals specific clinical
      significant immediate reaction to Balsam Peru. After adequate substitutional
      therapy was advocated and with specific clinical avoidance of offended allergen,
      remission was obtained. The second case was a 46 year old female suffering from
      chronic urticaria (with clinical features of urticaria like vasculitis)
      associated with hypocomplementemia (particularly C4 depressed) with negative
      antinuclear antibodies but positive circulating immune complexes after a 2 year
      follow up the patient developed Systemic lupus erythematosus. The third case was
      a 63 year old woman who developed chronic urticaria 3 years after total
      thyroidectomy, with pathological finding of Thyroiditis lymphocytaria-Hashimoto;
      after the allergological testing, positive lymphocyte transformation test
      revealed allergical sensitization to Vobenol was substituted with Thyvoral,
      complete remission was obtained.

PMID- 7565343
TI  - Quantitative mammography contrast threshold test tool.
AB  - Mammographic contrast is commonly evaluated by visualizing small objects of
      varying size or mass divided by projected area. These qualitative contrast
      determinations are commonly performed by imaging a phantom like the American
      College of Radiology accreditation phantom at clinical mammographic settings.
      However, this contrast assessment does not take into account the kVp of the
      machine. This work describes a quantitative mammography contrast threshold test
      tool which examines light object contrast on a uniform background for a contrast
      range of 0.32% to 1.38% at 25 kVp. For this mammography contrast threshold test
      tool, contrast is defined by delta I/I = loge (psi O/ psi b), where psi O is the
      target energy flux, and psi b is the background energy flux. Contrast threshold
      is defined as the lowest contrast value for which the objects are visible. Unlike
      traditional assessments of mammographic contrast, this measurement of contrast
      threshold is kVp corrected. The mammography contrast threshold test tool is
      constructed out of common plastics and provides a quantitative means of assessing
      contrast threshold for individual mammographic units and total mammographic
      systems.

PMID- 7565344
TI  - Quantitative versus subjective evaluation of mammography accreditation phantom
      images.
AB  - The precision of quantitative and subjective evaluations of phantom image quality
      has been studied. Twenty-seven images of the American College of Radiology (ACR)
      mammography accreditation phantom were acquired under different x-ray techniques
      and digitized. Several quantitative image quality measures were obtained from
      each image by analyzing microcalcification and nodule target objects in the
      phantom. All images were also scored subjectively by 8 observers, each of whom
      provided a count of the number of objects seen in each target class (fibrils,
      microcalcifications, and nodules). An analysis was performed to predict the
      subjective measurements from the quantitative measurements and to estimate their
      variabilities. It was found that the subjective measures could be well predicted
      by the quantitative measures and that the variance of the quantitative measures
      was significantly smaller than that of the subjective measure, by almost a factor
      of 10. The implication for the ACR accreditation program for mammography is that
      a substantial improvement is possible in the image quality evaluation process by
      performing computerized analysis of the phantom images in addition to subjective
      analysis.

PMID- 7565345
TI  - Segmentation of mammograms using multiple linked self-organizing neural networks.
AB  - A possible first stage in the analysis of the mammographic scene is its
      segmentation into four major components: background (the nonbreast area),
      pectoral muscle, fibroglandular region (parenchyma), and adipose region. An
      algorithm has been developed for this task. It is based on the classification of
      a feature vector constructed from statistical measures of texture calculated at
      two window sizes. Separate self-organizing neural networks are trained on sample
      data taken from each of the four regions. The feature vectors from the entire
      mammogram are then classified with the trained networks linked via a decision
      logic. To overcome the variability of texture between mammograms the algorithm
      uses data from a mammogram to classify itself in a staged approach consisting of
      several binary decisions. The training regions for each successive stage are
      determined from geometric information produced by the previous stages. The
      dataset in the study consisted of thirty (fifteen pairs) digitized normal
      mammograms of variable radiographic appearance. As a measure of performance, the
      outlines of the parenchyma were compared to those drawn by a radiologist
      experienced in reading mammograms. Comparison of the areas and perimeters
      generated by the human and computer observers gives a relationship with
      correlation coefficients of 0.74 and 0.59 for each measure, respectively. The
      overlapping areas of the parenchymas segmented by the observers normalized by the
      combined area was also calculated for each case. The mean and standard deviation
      of this measure was 0.69 +/- 0.12.

PMID- 7565346
TI  - X-ray imaging with amorphous selenium: detective quantum efficiency of
      photoconductive receptors for digital mammography.
AB  - Factors affecting the zero spatial frequency detective quantum efficiency of
      photoconductor-based x-ray detectors operating in the mammographic energy range
      are modeled for monoenergetic incident x rays. The problem is separated into two
      sections: the calculation of the x-ray absorption and the Swank factor. X-ray
      absorption in this energy range, for most practical photoconductors, is dominated
      by the photoelectric effect. The Swank factor has four components: fluorescence
      escape, stochastic variations in gain, variations of gain due to incomplete
      coupling of charge from the photoconductive layer to the detector electrode, and
      the nonlinear discharge arising from the field-dependent x-ray gain, an effect
      that is unique to photoconductors. Calculations are performed for selenium, which
      is currently the most technologically advanced photoconductor available for
      digital x-ray imaging. For thicknesses of selenium exceeding 50 microns and for
      energies between 12 and 50 keV, the detective quantum efficiency of this
      photoconductor is found to exceed that of a conventional Gd2O2S-based
      mammographic phosphor screen.

PMID- 7565348
TI  - Effects of undersampling on the proper interpretation of modulation transfer
      function, noise power spectra, and noise equivalent quanta of digital imaging
      systems.
AB  - The proper understanding of modulation transfer function (MTF), noise power
      spectra (NPS), and noise equivalent quanta (NEQ) in digital systems is
      significantly hampered when the systems are undersampled. Undersampling leads to
      three significant complications: (1) MTF and NPS do not behave as transfer
      amplitude and variance, respectively, of a single sinusoid, (2) the response of a
      digital system to a delta function is not spatially invariant and therefore does
      not fulfill certain technical requirements of classical analysis, and (3) NEQ
      loses its common meaning as maximum available SNR2 (signal-to-noise) at a
      particular frequency. These three complications cause the comparisons of MTF and
      NEQ between undersampled digital systems to depend on the frequency content of
      the images being evaluated. A tutorial of MTF, NPS, and NEQ concepts for digital
      systems is presented, along with a complete theoretical treatment of the above
      mentioned complications from undersampling.

PMID- 7565347
TI  - Image feature analysis and computer-aided diagnosis in mammography: reduction of
      false-positive clustered microcalcifications using local edge-gradient analysis.
AB  - To improve the performance of a computerized scheme for detection of clustered
      microcalcifications in digitized mammograms, causes of detected false-positive
      microcalcification signals were analyzed. The false positives were grouped into
      four categories, namely, microcalcification like noise patterns, artifacts,
      linear patterns, and others. In an edge-gradient analysis, local edge-gradient
      values at signal-perimeter pixels of detected microcalcification signals were
      determined to eliminate false positives that look like subtle microcalcifications
      or are due to artifacts. In a linear-pattern analysis, the degree of linearity
      for linear patterns was determined from local gradient values from a set of
      linear templates oriented in 16 different directions. Threshold values for the
      edge-gradient analysis and the linear-pattern analysis were determined using a
      training database of 39 mammograms. It was possible to eliminate 59% and 25%,
      respectively, of 91 detected false-positive clusters with loss of only 3% of true
      positive clusters. The combination of the two methods further improved the scheme
      in eliminating a total of 73% of the false-positive clusters with loss of 3% of
      true-positive clusters. Using these thresholds, the two methods were evaluated on
      another database of 50 mammograms. 62%, 31%, and 80% of the false-positive
      clusters were eliminated with loss of 3% of true-positive clusters or less, in
      the edge-gradient analysis, the linear-pattern analysis, and the combination of
      the two methods, respectively. The edge-gradient analysis and the linear-pattern
      analysis can reduce the false-positive detection rate, while maintaining a high
      level of the sensitivity.

PMID- 7565349
TI  - A fully automated algorithm for the segmentation of lung fields on digital chest
      radiographic images.
AB  - A completely automated algorithm is presented which is capable of identifying
      both the right- and left-lung fields on digitized chest radiographic images. The
      algorithm is tested on a sample of 802 chest images against lung fields drawn by
      a human observer. The average accuracies are found to be 0.957 +/- 0.003 and
      0.960 +/- 0.003 for right- and left-lung regions, respectively. To put them into
      perspective, the results are compared to several other simple segmentation
      techniques. These include a comparison of two sets of lung fields drawn by the
      human observer at different times which yielded accuracies of 0.967 +/- 0.005 and
      0.967 +/- 0.004 for right- and left-lung regions, respectively.

PMID- 7565350
TI  - Comparison of two methods for accurate measurement of modulation transfer
      functions of screen-film systems.
AB  - The modulation transfer function (MTF) of a screen-film system can be measured by
      two methods, i.e., a slit method with Fourier transform on the line spread
      function and a square-wave response function (SWRF) method. However, it is still
      uncertain whether MTFs obtained by the two methods are identical. In this study,
      MTFs of relatively sharp and unsharp screen-film systems were measured by using
      the two methods. The slit method provided slightly greater MTF for the relatively
      sharp system than the SWRF method. However, MTFs of the unsharp system obtained
      with the two methods were comparable. Generally, the slit method tends to provide
      reliable results for unsharp systems, whereas the SWRF method is favorable for
      sharp systems. Accuracy and consistency of these measurements were examined by
      comparison of experimental and theoretical edge responses derived from the
      measured MTFs. However, the difference in edge responses obtained by the two
      methods was relatively small compared with the variation of the measured edge
      responses, and thus results were considered inconclusive as to whether either of
      the methods can provide more accurate MTFs. International interlaboratory
      comparison indicated that the variation in the measured MTFs at six different
      institutions was relatively large for both methods. However, the MTFs of two
      screen-film systems measured by the slit method appear to agree with those by the
      SWRF method within the variation expected from the interlaboratory comparison.

PMID- 7565351
TI  - The spatial resolution performance of a time-resolved optical imaging system
      using temporal extrapolation.
AB  - Optical imaging methods are being explored as a potential means of screening for
      breast cancer. Previous investigations of time-resolved imaging techniques have
      suggested that due to the lack of photons with sufficiently small pathlengths,
      the spatial resolution achievable through a human breast would be unlikely to be
      better than a centimeter. Experimental results presented here indicate, however,
      that higher resolution may be achieved by extrapolating the measured temporal
      distribution of transmitted photons. This is performed using a least-squares fit
      between data and an analytic model of photon transport. The spatial resolution of
      a time-resolved imaging system was evaluated by measuring the edge response
      produced by an opaque mask embedded in the center of a 51-mm-thick, very highly
      scattering medium. The limiting spatial resolution was improved from about 13 mm
      to about 5 mm.

PMID- 7565354
TI  - On visual interpretation of light localization/radiation field coincidence films.

PMID- 7565353
TI  - Radioactive check device for ionization chambers.

PMID- 7565355
TI  - A method for modifying a commercial extended travel range patient support
      assembly to achieve controlled rotation during arc therapy.

PMID- 7565352
TI  - Dosimetry of interstitial brachytherapy sources: recommendations of the AAPM
      Radiation Therapy Committee Task Group No. 43. American Association of Physicists
      in Medicine.

PMID- 7565356
TI  - Dosimetric characteristics of a commercial multileaf collimator.
AB  - The dosimetric characteristics of a multileaf collimator (MLC) retrofitted to a
      SL25 linear accelerator have been investigated. Central-axis depth dose, surface
      dose, penumbra, beam flatness and symmetry, field size factors, beam transmission
      through leaves and/or diaphragms, and leakage between the leaves were measured.
      Quantitative measurements of all beam parameters show good agreement with the
      design specifications of the manufacturer. No changes were observed in flatness,
      symmetry, penumbra, and penetration for both 6- and 25-MV photon beams when
      compared to the values for the standard collimator. No significant differences
      were observed in the penumbra as a function of leaf position. Transmission
      measurements in areas shielded by either X diaphragms or leaves plus diaphragms
      are less than 1% of dose within open field. The average leakage between leaves is
      about 2.5% for 6-MV and 3.5% for 25-MV photon beams. The peak value of the
      leakage at any point between leaves is less than 5%. The dosimetric features of
      shaped fields using the MLC are comparable to those of alloy shaped fields with
      the standard SL25 collimator.

PMID- 7565357
TI  - Intercomparison of normalized head-scatter factor measurement techniques.
AB  - Normalized head-scatter factors were measured with cylindrical beam coaxial
      miniphantoms and high purity graphite buildup caps for 4-, 6-, 10-, and 24-MV
      photon beams at field sizes from 4 x 4 to 40 x 40 cm2. The normalized head
      scatter factors determined by the two methods matched well for 4- and 6-MV photon
      beams. The miniphantom technique produced normalized head-scatter factors 1.5%
      and 4.8% lower than the buildup caps for the 10- and 24-MV beams for large field
      sizes, respectively. At small field sizes, the miniphantom technique produced
      larger normalized head-scatter factors than the buildup caps. Measurements made
      with an electromagnet indicate that a significant portion of the ionization
      measured in the buildup cap at 24 MV arises from contamination electrons.
      Measurements made with the miniphantom and magnet found no contamination electron
      contribution. The miniphantom technique may exclude such contamination electrons,
      potentially leading to inaccuracies in tissue-maximum ratios and phantom scatter
      factors, as well as inaccuracies in monitor unit calculations.

PMID- 7565358
TI  - Spatially varying optical property reconstruction using a finite element
      diffusion equation approximation.
AB  - A finite element reconstruction algorithm for optical data based on a diffusion
      equation approximation is presented. A frequency domain approach is adopted and a
      unified formulation for three combinations of boundary observables and conditions
      is described. A multidetector, multisource measurement and excitation strategy is
      simulated, which includes a distributed model of the light source that
      illustrates the flexibility of the methodology to modeling adaptations.
      Simultaneous reconstruction of both absorption and scattering coefficients for a
      tissue-like medium is achieved for all three boundary data types. The algorithm
      is found to be computationally practical, and can be implemented without major
      difficulties in a workstation computing environment. Results using simulated data
      suggest that qualitative images can be produced that readily highlight the
      location of absorption and scattering heterogeneities within a circular
      background region of close to 4 cm in diameter over a range of contrast levels.
      Absorption images appear to more closely identify the true size of the
      heterogeneity; however, both the absorption and scattering reconstructions have
      difficulty with sharp transitions at increasing depth. Quantitatively, the
      reconstructions are not accurate, suggesting that absolute optical imaging
      involving simultaneous recovery of both absorption and scattering profiles in
      multicentimeter tissues geometries may prove to be extremely difficult.

PMID- 7565359
TI  - Collimator optimization for lesion detection incorporating prior information
      about lesion size.
AB  - A Bayesian estimator has been developed as a paradigm for human observer
      performance in detecting lesions of unknown size in a uniform noisy background.
      The Bayesian observer used knowledge of the range of possible lesion sizes as a
      prior; its predictions agreed well with the results of a six-observer perceptual
      study. The average human response to changes in collimator resolution, as
      measured by the detectability index, dA, was tracked by the Bayesian detector's
      signal-to-noise ratio (SNR) somewhat better than by two other estimation models
      based, respectively, on lesser and greater degrees of lesion size uncertainty. As
      the range of possible lesion sizes increased, the Bayesian detector's SNR
      decreased and the optimal collimator resolution shifted towards better
      resolution. An analytic approximation for the variance of lesion activity
      estimates (which included the same prior) was shown to predict the variance of
      the Bayesian estimator over a wide range of collimator resolution values. Because
      the bias of the Bayesian estimator was small (< 1%), the analytic variance
      estimate permitted a rapid and convenient prediction of the Bayesian detection
      SNR. This calculation was then used to optimize the geometric parameters of a two
      layer tungsten collimator being constructed from crossed grids for a new imaging
      detector. A Monte Carlo program was first run to estimate all contributions to
      the radial point-spread function for collimators of differing tungsten contents
      and spatial resolution values, imaging 140-keV photons emitted from the center of
      a 15-cm-diameter, water-filled attenuator. The optimal collimator design for
      detecting lesions with unknown diameters in the range 2.5-7.5 mm yielded a system
      resolution of approximately 8.5-mm FWHM, a geometric collimator efficiency of
      1.21 x 10(-4), and a single-septum penetration probability of 1%.

PMID- 7565361
TI  - An algorithm for improving the accuracy of discrete ROI integrals.
AB  - Many problems in the analysis of medical digital images, e.g., digitized x-ray
      radiograph, computed tomography (CT), magnetic resonance imaging (MRI), or
      positron emission tomography (PET), require a detailed and precise analysis of
      user chosen regions of interest (ROIs). Examples of their use include calculating
      integrals of area, volume, mass, structural moments, and statistical measures for
      either organs, tumors, or the musculoskeletal system. Among various ROI scan
      conversion schemes, binary approximate scan conversion is usually preferred due
      to its efficiency. In this paper, geometric area error is tabulated for typical
      scan conversion techniques, including whole pixel (WP) approximation and subpixel
      (SP) approximation methods, and compared to exact pixel (EP) coverage methods for
      medical ROIs. A new efficient and general EP method for scan conversion of these
      ROIs is presented. The algorithm traverses the boundary of the polygon while
      simultaneously scan converting the ROI, and calculates the fractional area of
      each pixel covered at the perimeter. The resultant geometric area is
      substantially more accurate than the SP or WP methods, without a significant loss
      of speed. The numerical results for a ROI with a large ratio of boundary to
      polygon area demonstrated that the geometric error for a SP method was 40% of the
      total polygon area, and 150% of the total polygon area for a WP method. The new
      algorithm could "exactly" calculate the pixel coverage area, in addition to being
      four times faster than the widely used EP method of Catmull. Efficient and
      accurate calculation of ROI integrals is essential for comparative analysis.

PMID- 7565362
TI  - The geometric modulation transfer function of a transmission imaging system that
      uses a SPECT scintillation camera and parallel hole collimation.
AB  - An analytic expression has been derived to calculate the geometric modulation
      transfer function of a transmission imaging system that uses parallel hole
      collimation for both the source and the SPECT camera. This expression describes
      the resolution of the transmission imaging system and replaces the need to use
      computer intensive Monte Carlo simulations for the system design. The geometric
      modulation transfer function, denoted as MTFg(rho) = [A2sc(Ssc rho)**A2cc(Scc
      rho)]D(rho), where ** denotes two-dimensional convolution; Asc(rho) and Acc(rho)
      are the Fourier transforms (FT) of the aperture functions for the parallel hole
      source collimator (SC) and the camera collimator (CC) holes, respectively; D(rho)
      is the FT of the camera response; and ssc and scc are scaling constants that
      depend on the respective collimator dimensions, the system dimensions, the object
      distance above camera collimator and whether MTFg(rho) is calculated for the
      object or image plane. The theoretical MTFg(rho) was verified with Monte Carlo
      simulations and experimental results. The formalism shows that the system
      resolution is characterized by the camera resolution and a combination of the
      resolutions of the source and camera collimators. This expression can be used to
      optimize the design of transmission imaging systems to be used in nuclear
      medicine.

PMID- 7565360
TI  - Contrast-detail analysis of image degradation due to lossy compression.
AB  - A contrast-detail (CD) experiment was performed to study the effect of lossy
      compression on computed radiographic (CR) images. Digital CR images of a phantom
      were compressed by quantizing the full-frame discrete cosine transform and
      Huffman encoding the result. Since low-contrast detectability is directly linked
      to an important radiological task, namely, the detection of noncalcified
      pulmonary nodules in adult chest radiographs, the goal of the study was to
      quantify any loss in low-contrast detectability due to compression. Compression
      ratios varied significantly among compressed images, despite the use of fixed
      compression parameters; detectability could be specified by a single parameter of
      a CD curve; there was no significant reduction in detectability for an average
      compression ratio of 11:1; and, there was a statistically significant degradation
      in detectability for an average compression ratio of 125:1.

PMID- 7565365
TI  - Backscatter dose perturbation in kilovoltage photon beams at high atomic number
      interfaces.
AB  - Dose perturbations at tissue interfaces have been of significant concern since
      the beginning of this century. However, comprehensive studies related to the
      backscatter perturbation in kilovoltage beams are still limited. The dose
      perturbation depends on various parameters, including beam energy, field size,
      and the thickness, width, position, and atomic number, Z, of the inhomogeneity
      creating the interface with soft tissue. Using a thin window parallel plate ion
      chamber having relatively flat response at low energies, the dose perturbation
      was measured as backscatter dose perturbation factor, BSDF, at various interfaces
      in kilovoltage x-ray beams. The BSDF is defined as the ratio of doses with and
      without an interface for identical setup conditions. Results indicate that the
      BSDF is strongly dependent on beam energy, like the backscatter factor. Contrary
      to its behavior in megavoltage beams, BSDF in kilovoltage beams does depend on
      the field size, suggesting a contribution from scattered photons and fluorescent
      radiation, originating in the high-Z material. The thickness of the high-Z medium
      is not critical, since a fraction of a millimeter is sufficient to provide full
      backscatter. The interface effect with wide inhomogeneity has two distinct
      regions: the high dose region (BSDF > 1.0), which is very localized and
      disappears within a fraction of a millimeter, and the low dose region (BSDF <
      1.0), which is observed up to 10 cm. The dependence of BSDF is neither a
      quadratic function of Z nor a cube root of beam energy, indicating that the
      interface effect is complex and not predominantly due to photoelectron transport.

PMID- 7565366
TI  - Determination of differential scatter-air ratios (dSAR) for three-dimensional
      scatter integration.
AB  - Scatter dose may be calculated by summing the scatter contribution from
      individual volume elements. These contributions may be represented by
      differential scatter-air ratios (dSAR). Determination of dSAR from measured data
      is only approximately correct for second and higher orders of scatter and yields
      values often limited to one significant figure. Monte Carlo calculation, on the
      other hand, is time intensive, requires some knowledge of the beam's x-ray
      spectrum, and mastering the complexities of a program such as EGS4. Total scatter
      dose at a point may be determined by measuring depth dose or tissue-air ratios
      and partitioning the dose into its primary and scatter components. Scatter may be
      represented by scatter-air ratios, which can be characterized by the sum of
      first, second, and higher orders of scatter. The first scatter dose may be
      computed exactly by summing the first scatter contribution from individual
      elements, determined from the first principle. Separation of dSAR into primary
      attenuation and depth-independent terms allows the latter to be precomputed once
      for a given energy and stored in tabular form. Second scatter may be treated in a
      similar manner. The higher orders of scatter are computed by subtracting the sum
      of calculated first and second scatter doses from the total scatter dose.
      Elements close to and approximately 1 cm above the point of calculation
      contribute most heavily to the first scatter dose. Compared to the first scatter
      dose, the second scatter dose contribution is lower, particularly for elements
      close to the point of calculation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565363
TI  - Radiation dose distribution within the bone marrow of patients receiving holmium
      166-labeled-phosphonate for marrow ablation.
AB  - The primary objective of this work was to estimate the absorbed dose distribution
      to the bone marrow of six multiple myeloma patients who received holmium-166
      (166Ho) DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic
      acid) for the purpose of bone marrow ablation. A methodology based on gamma
      camera images was developed to estimate the regional absorbed dose distributions
      delivered to the bone marrow, and this was compared with values calculated from
      the MIRD technique and bone marrow biopsies. The activity concentration in
      various skeletal regions was calculated from the activity in the region of
      interest (ROI) drawn on whole body gamma camera images, and the mass of bone in
      each ROI was derived from a dual x-ray absorptiometry image. The radiation
      absorbed dose to the bone marrow was calculated from this activity concentration
      using an adaptation of Bragg-Gray cavity theory. The radiation absorbed dose
      delivered to the bone marrow in the six patients calculated from the MIRD "S"
      factors ranged from 15.0 to 46.3 Gy. The gamma camera measured activity
      concentration in skeletal regions predominantly composed of trabecular bone was
      approximately five to six times higher than that in cortical regions. The
      skeletal activity concentration in each patient ranged from highs in such regions
      as the ribs to lows in such regions as the shin and foot by a factor of nearly
      20, producing a heterogeneous distribution of absorbed dose within the marrow.
      Dose volume histograms calculated for these patients indicated that 15%-20% of
      the marrow received an absorbed dose significantly larger than the average value,
      while 5%-10% of the marrow received a substantially lower dose. Weighted mean
      dose estimates from the regional technique were typically 30% greater than the
      average dose estimates calculated with the MIRD "S" factors. Finally, absorbed
      dose estimates for the marrow calculated from the regional technique correlated
      more closely with the clinical response of blood cells and abnormal proteins
      measured in bone marrow aspirates and peripheral blood samples than estimates
      from the MIRD "S" factors.

PMID- 7565364
TI  - Performance evaluation of annular arrays in practice: the measurement of phase
      and amplitude patterns of radio-frequency deep body applicators.
AB  - An approach to a solution of two major problems in operating Annular Phased
      Arrays in deep body hyperthermia is presented: an E-field sensor capable of
      measuring phase and amplitude at 70 MHz and the concept of a power transmission
      factor to determine the effective amplitude of each applicator. In the four
      waveguide Phased Array operating at 70 MHz, which is in clinical use at the
      department of Radiotherapy of the Academic Medical Center (AMC), the incident
      fields of the waveguides were scanned in phase and amplitude over the complete
      aperture midplane, inside an elliptical and a square phantom filled with saline.
      As a check on the application of the superposition principle, superpositions of
      the incident fields were compared with the electric field in the measured
      interference set-ups. With all four applicators radiating at equal amplitude and
      in phase, the maximum difference over the complete midplane of the phantom
      between superimposed and measured interference scans was 20% and 10 degrees in
      the elliptical phantom, and 20% and 30 degrees in the square phantom. After
      having determined nominal amplitude and phase patterns by a vector probe, any
      interference set-up can be superimposed from measurement of the actual incident
      field of each applicator. Therefore, the availability of a vector sensor as
      described here will contribute to solve a problem of hyperthermia quality
      assurance: the performance evaluation of Phased Arrays.

PMID- 7565367
TI  - Beam characteristics of a new generation 50 MeV racetrack microtron.
AB  - The first of a new generation of microtron accelerators has been installed and
      tested. It is currently in use for multisegment conformal radiotherapy at our
      institution. The unit produces x rays and electrons from 10 to 50 MeV in 5 MeV
      increments. It incorporates a 64 leaf, doubly focused multileaf collimator (MLC),
      which can be used to shape x-ray and electron beams. Both x-ray and electron
      beams are produced by magnetically scanning the electron beams from the
      accelerator. The new generation unit incorporates a purging magnet to sweep away
      any primary or secondary electrons that pass through the target(s). In this
      paper, the beam characteristics of the accelerator that were studied during
      acceptance testing are described. Representative examples of depth doses, beam
      profiles, output factors, and elementary beam distributions are presented and
      discussed, in comparison with the earlier generation of microtron accelerators
      and with other radiotherapy machines.

PMID- 7565368
TI  - X-ray source and the output factor.
AB  - When the collimator setting of a linear accelerator is made sufficiently small,
      the output factor in air, R, is greatly reduced because the collimators obstruct
      the periphery of the x-ray source. This has been utilized to examine the size of
      the source by varying the width y of a narrow field and determining how R(y)
      varies. The sources diameters in the two principal directions were clearly
      influenced by the design of the accelerators. The x-ray sources of two
      accelerators with bending magnets were found to be noncircular while that of a
      linear accelerator without a magnet showed circular symmetry. The position of the
      source relative to the axis of collimator rotation was determined by measuring R
      for offset narrow fields. For one of the accelerators, the source was initially
      moving and off the central axis by about 2 mm for the first five monitor units.
      The results correlated well with sharpness in portal-film images. The technique
      can serve to evaluate the major source characteristics in acceptance testing and
      quality control.

PMID- 7565369
TI  - A novel comprehensive quality control instrument for medical accelerators.
AB  - A comprehensive quality control instrument for calibration of medical
      accelerators that use photon, electron, or proton beams in teleradiotherapy is
      described. It employs a fluorescence screen, mounted on a central stage with four
      degrees of freedom, monitored by a CCD camera. A single set-up of the instrument
      enables one to perform mechanical, light laser, and radiation tests, at arbitrary
      angles of the accelerator gantry. The new device provides for quantitative
      evaluation of the tests performed and provides for documentation of the test
      results in real time. The device provides significant time savings with
      concurrent improvement in accuracy for tests performed during installation and
      acceptance processes, and the implementation of quality control procedures for
      medical accelerators.

PMID- 7565370
TI  - Physical penumbra change of beam profile due to film digitization.

PMID- 7565371
TI  - Disturbance of diode dosimetry by radiofrequency radiation.

PMID- 7565372
TI  - Monte Carlo aided dosimetry of the microselectron pulsed and high dose-rate 192Ir
      sources.
AB  - Despite the large number of single-stepping source pulsed and high dose-rate
      (HDR) remote after-loading devices in clinical use, the published literature
      contain little data characterizing dose-rate distributions around the high
      intensity (4 x 10(3)-4 x 10(4) microGy m2h-1) 192Ir sources currently used in
      these devices. We have used the Monte Carlo method to calculate complete two
      dimensional dose-rate distributions about the most widely used high dose-rate
      source design, as well as the Nucletron pulsed dose-rate (PDR) 192Ir source. A
      Monte Carlo photon transport code, incorporating the detailed internal geometry
      of the source, was used to calculate the dose rate per unit air-kerma strength in
      water medium on the transverse bisecting axis over the 0.15-12 cm distance range.
      In addition, polar dose profiles were calculated at distances ranging from 0.25
      to 5 cm. The PDR and HDR dose-rate distributions are tabulated using the
      formalism endorsed by the Interstitial Collaborative Working Group and the AAPM
      Task Group 43, and includes dose-rate constant, radial dose function, anisotropy
      function, geometry function, and anisotropy factors. The dose-rate constants,
      lambda, of the MicroSelectron/HDR and PDR sources were found to be 1.115 and
      1.128 cGy h-1 per unit air-kerma strength, respectively, in good agreement with
      previously published data for low dose-rate interstitial 192Ir sources. Oblique
      filtration by the high-density iridium metal core resulted in deviations from
      anisotropy as large as 35%-55% near the longitudinal axis of the source. Dose
      rate distributions are also presented in Cartesian ("away" and "along")
      coordinates.

PMID- 7565373
TI  - Experimental validation of Monte Carlo dose calculations about a high-intensity
      Ir-192 source for pulsed dose-rate brachytherapy.
AB  - Despite widespread use of high-intensity Ir-192 remotely afterloaded sources, no
      published measured or calculated dose-rate tables for currently used source
      designs are available. For a pulsed dose-rate Ir-192 source, both transverse axis
      (0.5-10 cm) and two-dimensional polar dose-rate profiles (1.5, 3, and 5 cm) were
      measured with thermoluminescent dosimetry in a solid water phantom. Dose rates
      were normalized to measured air-kerma strength, and the source geometry was
      verified by pinhole autoradiography and transmission radiography. At each
      measurement point, dose rates were calculated by a Monte Carlo photon transport
      (MCPT) code, which realistically modeled the experimental phantom, source, and
      detector geometry. Agreement between MCPT absolute dose-rate calculations and
      measurements averaged 3% and was less than 5%, demonstrating that Monte Carlo
      simulation is an accurate and powerful tool for two-dimensional dosimetric
      characterization of high activity Ir-192 sources.

PMID- 7565374
TI  - Measurements of the effect of storage at various temperatures on the T1 of ex
      vivo tissues.
AB  - The detailed measurements of the effects of storage at various temperatures on
      the nuclear magnetic resonance (NMR) spin-lattice relaxation time T1 are
      reported. On the basis of the results, a method to monitor tissue transformation
      in hyperthermia of biological systems using magnetic resonance imaging (MRI)
      techniques is discussed. The method was found on proton relaxation time spin
      lattice T1 variation measurements. Parameter F described as tissue structure
      transformation and/or protein denaturation rate index is discussed.

PMID- 7565375
TI  - p-type silicon detector for brachytherapy dosimetry.
AB  - The sensitivity of a cylindrical p-type silicon detector was studied by means of
      air and water measurements using different photon beams. A lead filter cap around
      the diode was used to minimize the dependence of the detector response as a
      function of the brachytherapy photon energy. The radial dose distribution of a
      high-activity 192Ir source in a brachytherapy phantom was measured by means of
      the shielded diode and the agreement of these data with theoretical evaluations
      confirms the method used to compensate diode response in the intermediate energy
      range. The diode sensitivity was constant over a wide range of dose rates of
      clinical interest; this allowed one to have a small detector calibrated in terms
      of absorbed dose in a medium. Theoretical evaluations showed that a single
      shielding filter around the p-type diode is sufficient to obtain accurate
      dosimetry for 192Ir, 137Cs, and 60Co brachytherapy sources.

PMID- 7565376
TI  - Rutherford's curriculum vitae, 1894-1907.
AB  - A single page, handwritten document was discovered when the Macdonald Physics
      building of McGill University in Montreal was gutted in 1978. This proved to be
      the draft of Ernest Rutherford's curriculum vitae (C.V.) covering the years 1894
      1907, probably written in the autumn of 1906 when Rutherford was preparing to
      leave McGill. The C.V. contains 21 headings in chronological order, referring to
      research and other activities of Rutherford and his coauthors (especially Soddy
      and Barnes), plus a further set of headings relating to the associated
      investigations of Rutherford's team, including Eve and Hahn. A transcript of the
      document is provided, although in several places, Rutherford's handwriting is
      difficult to interpret, and the significance of his abbreviations is not always
      clear. Each of the items in the C.V. is discussed briefly in this review, in the
      light both of Rutherford's personal career and of the contribution of his team to
      the development and understanding of radioactivity. This contribution included
      the cause and nature of radioactivity (with Soddy), energy aspects of radioactive
      decay (with Barnes), elucidation of the uranium-radium, thorium and actinium
      series (Godlewski and Hahn), the radioactivity of the earth and atmosphere (Eve),
      the nature of the gamma rays (Eve) and, perhaps most important of all, the nature
      and properties of the alpha particle (Rutherford himself). The latter
      investigations led directly to Rutherford's later work in Manchester, including
      the nuclear model of the atom and artificial disintegration of the nucleus.

PMID- 7565377
TI  - Filter wheel equalization for chest radiography: a computer simulation.
AB  - A chest radiographic equalization system using lung-shaped templates mounted on
      filter wheels is under development. Using this technique, 25 lung templates for
      each lung are available on two computer controlled wheels which are located in
      close proximity to the x-ray tube. The large magnification factor (> 10X) of the
      templates assures low-frequency equalization due to the blurring of the focal
      spot. A low-dose image is acquired without templates using a (generic) digital
      receptor, the image is analyzed, and the left and right lung fields are
      automatically identified using software developed for this purpose. The most
      appropriate left and right lung templates are independently selected and are
      positioned into the field of view at the proper location under computer control.
      Once the templates are positioned, acquisition of the equalized radiographic
      image onto film commences at clinical exposure levels. The templates reduce the
      exposure to the lung fields by attenuating a fraction of the incident x-ray
      fluence so that the exposure to the mediastinum and diaphragm areas can be
      increased without overexposing the lungs. A data base of 824 digitized chest
      radiographs was used to determine the shape of the specific lung templates, for
      both left and right lung fields. A second independent data base of 208 images was
      used to test the performance of the templates using computer simulations. The
      template shape characteristics derived from the clinical image data base are
      demonstrated. The detected exposure in the lung fields on conventional chest
      radiographs was found to be, on average, three times the detected exposure behind
      the diaphragm and mediastinum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565380
TI  - Toward consensus on quantitative assessment of medical imaging systems.
AB  - Consensus has been developing over the past few decades on a number of
      measurements required for the laboratory assessment of medical imaging
      modalities. Nevertheless, understanding of the connection between these
      measurements and human observer performance in a broad range of tasks remains far
      from complete. Focusing primarily on projection radiography to provide concrete
      examples, this overview indicates areas in which consensus on methodology for
      physical image-quality measurement has been established. Concepts such as "noise
      equivalent quanta" (NEQ) and "detective quantum efficiency" (DQE) have been found
      useful for normalizing physical measurements on an absolute scale and for
      relating those measurements to the decision performance of a hypothetical "ideal
      observer" that effectively performs decision tasks from the image data. The
      connection between ideal observer performance and human performance, as
      determined by receiver operating characteristic (ROC) analysis, remains to be
      understood for many clinically relevant tasks.

PMID- 7565378
TI  - Beam hardening errors in post-processing dual energy quantitative computed
      tomography.
AB  - A computer simulation study was performed to assess the errors due to x-ray beam
      hardening in the fat and bone estimates of a post-processing dual-energy
      quantitative computed tomography technique. The "central" calibration method was
      employed in which calibration standards are inserted within a torso phantom of a
      size similar to that of the "patient." Although beam hardening errors are reduced
      with this method, they still occur as a result of mismatches between the torso
      phantom and patient body sizes. Two mismatch situations were investigated. In
      one, a single torso phantom was used for all subject sizes (i.e., one-size-fits
      all). In the other, closest matches were made from a set of three different sized
      torso phantoms (small, medium, and large). In all cases, the compositions of the
      calibration standards that were inserted into the torso phantoms consisted of
      bone, fat (glycerol trioleate), and an average fat-free red marrow. Fifteen
      patient sizes were simulated ranging from 20 to 34 cm in diameter. There were 21
      patients of each size. The vertebrae in these subjects contained known amounts of
      bone mixed in marrows of composition determined from chemical analyses of cadaver
      marrow samples. Vertebrae consisting of mixtures of the calibration standard
      materials were also studied. The computed effective x-ray beam energies at the
      vertebra location for the various subject sizes ranged from 54.3 to 56.4 keV at
      80 kVp and from 74.4 to 78.8 keV at 140 kVp.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565379
TI  - Registration error quantification of a surface-based multimodality image fusion
      system.
AB  - This paper presents a new reference data set and associated quantification
      methodology to assess the accuracy of registration of computerized tomography
      (CT) and magnetic-resonance (MR) images. Also described is a new semiautomatic
      surface-based system for registering and visualizing CT and MR images. The
      registration error of the system was determined using a reference data set that
      was obtained from a cadaver in which rigid fiducial tubes were inserted prior to
      imaging. Registration error was measured as the distance between an analytic
      expression for each fiducial tube in one image set and transformed samples of the
      corresponding tube obtained from the other. Registration was accomplished by
      first identifying surfaces of similar anatomic structures in each image set. A
      transformation that best registered these structures was determined using a
      nonlinear optimization procedure. Even though the root-mean-square (rms) distance
      at the registered surfaces was similar to that reported by other groups, it was
      found that rms distances for the tubes were significantly larger than the final
      rms distances between the registered surfaces. It was also found that minimizing
      rms distance at the surface did not minimize rms distance for the tubes.

PMID- 7565381
TI  - Digital portal image registration by sequential anatomical matchpoint and image
      correlations for real-time continuous field alignment verification.
AB  - Detection of radiotherapy field misalignments with electronic portal imaging
      devices requires the precise initial registration of the digital portal image
      with a reference image indicating the prescribed field alignment. Moreover, for
      real-time continuous detection this registration must be performed rapidly-
      arguably within 250 ms. The quality of this registration is sensitive to the
      ability of the user to accurately identify corresponding anatomical landmarks in
      the image pair. To improve the accuracy of the registration and, ultimately, that
      of the field misalignment measurement, we have developed a sequential digital
      portal image registration method using both user-identified anatomical
      matchpoints and image information. A first pass generates registration parameters
      from user-provided matchpoint coordinates and explicitly accounts for the
      uncertainty in matchpoint identification. The second pass uses both the initial
      registration parameters and image information to further improve the registration
      quality by maximizing cross correlations between segments of the image pair. As
      this registration method does not use massive matrix/vector computations common
      to other algorithms, it is inherently faster and well-suited for real-time field
      placement error detection. On a platform representative of those controlling many
      commercial electronic portal imaging devices (486 CPU), this algorithm registers
      portal images in times of less than 6 ms per matchpoint with errors of less than
      2% in magnification, 0.5 degree in in-plane rotation, and less than 1 pixel
      dimension in in-plane translation. As the algorithm assumes a rigid-body
      geometry, it is sensitive to out-of-plane rotations. A quantitative analysis of
      this algorithm is presented, indicates its accuracy, and describes its
      sensitivity to out-of-plane rotations.

PMID- 7565382
TI  - Monte Carlo studies of x-ray energy absorption and quantum noise in megavoltage
      transmission radiography.
AB  - The subject contrast of bony anatomy in megavoltage medical radiographs is very
      low, making detection of bony landmarks difficult if additional noise sources are
      introduced into the images. One source of noise, which is inherent to the x-ray
      detection process, is x-ray energy absorption noise. X-ray energy absorption
      noise results from variations in the amount of energy deposited in the imaging
      detector per interacting x ray. These variations increase the noise content of
      the image. In this study, EGS4 Monte Carlo simulations of x-ray interactions in
      metal plate phosphor screen detectors have been performed to determine the
      distribution of energy absorption events within the phosphor screen. From these
      "absorbed energy distributions (AEDs)", the x-ray energy absorption noise and the
      quantum absorption efficiency of the detector are determined. These calculations
      are performed for a range of detector thicknesses (0.1-4 mm) and x-ray energies
      (0.1-10 MeV). A number of conclusions can be drawn from these investigations. (i)
      The x-ray absorption noise reduces the detective quantum efficiency (DQE) of
      metal plate/phosphor screen detectors by as much as 50% at energies used in
      megavoltage imaging (1-10 MeV). (ii) It is important to include secondary
      particle (electron) transport in estimating the quantum absorption efficiency of
      these detectors. For instance, the quantum efficiency of a typical portal
      detector is approximately 2%, even though 4%-5% of the incident photons are
      attenuated. (iii) The metal "conversion" plate commonly used in megavoltage
      imaging enhances the DQE of the phosphor screen by increasing the quantum
      absorption efficiency and reducing the magnitude of the x-ray absorption noise.

PMID- 7565383
TI  - Optimization of automatic portal image analysis.
AB  - The purpose of this study is to quantify and optimize the performance of an
      automatic portal image analysis procedure under clinical conditions and to
      compare the performance with that of human operators. A new method, based on
      analysis of variance, is introduced to quantify the clinical performance of
      portal image analysis tools in terms of systematic and random variations. The
      automatic portal image analysis procedure is based on chamfer matching. Two image
      enhancement techniques have been investigated in the automatic procedure:
      morphological top-hat (MTH) transformation and multiscale medial axis (MMA)
      transformation. The performance of these enhancements was quantified and
      optimized as a function of filter size using images obtained from clinical
      treatment. All images used for this study were obtained from pelvic treatment
      fields by means of an electronic portal imaging device. The random variations in
      the alignment of AP fields are typically 0.5 mm and 0.5 degrees (1 SD) for both
      the human operators and the optimized automatic analysis procedure. Random
      variations in the alignment of lateral pelvic fields are typically twice as large
      for all operators. MMA enhancement yields smaller random variations than MTH
      enhancement for lateral fields, but the differences are marginal for AP fields.
      The optimized automatic analysis procedure has a success rate ranging from 99%
      for AP large fields to 96% for lateral fields and 85% for AP boost fields. The
      accuracy of the method is comparable with the accuracy of the human operators for
      most investigated fields. For lateral boost fields and simultaneous boost fields,
      the random variations of the automatic analysis are typically two times larger
      than the variations of the human operators. Automatic analysis is 4 to 20 times
      faster than human operators yielding a large reduction in work load.

PMID- 7565384
TI  - Portal dosimetry using a liquid ion chamber matrix: dose response studies.
AB  - Current intensive investigations of electronic portal imaging devices (EPIDs)
      have prompted their potential application to portal dosimetry. In this paper, the
      progress made in using a commercial liquid ion chamber matrix EPID for portal
      dosimetry is discussed. The pixel value of the liquid ion chamber element was
      calibrated against dose by exposing the imager to 6-MV x-ray beams of various
      intensities obtained with various thicknesses of lead attenuators and a range of
      source to detector distances. Absolute dose values were determined using an ion
      chamber on the central axis at the depth of maximum dose in a solid water
      phantom. The pixel values of the matrix were determined for various field sizes
      in order to evaluate the dependence of pixel value on dose at those field sizes.
      It was confirmed that the pixel value was proportional to the square root of the
      dose rate and was nearly independent of the field size. The 2D pixel values were
      converted to 2D dose maps in the water phantom after applying a correction for
      the effect of horns in the flood calibration field. The flood calibration field
      was used to obtain the relative sensitivity of each pixel. Good agreement was
      observed (normally better than 1% in relative standard deviation) between the
      converted dose distribution obtained from the pixel matrix and the direct dose
      measurement using an ion chamber scanned in a water phantom in regions of shallow
      dose gradient. For application to on-line portal dosimetry, both the short- and
      long-term stability of this EPID system were found to be within 1% relative
      standard deviation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565385
TI  - A mathematical model of radiation field edge localization.
AB  - A mathematical model of the average edge slope across the radiation field border
      in a portal image was investigated in order to improve the precision of edge
      localization in a previously reported algorithm for automatic extraction of the
      radiation field from double- and single-exposure portals. The model involves a
      global rather than a local approach to edge localization, and employs a
      hyperbolic function with four parameters to characterize the behavior of the
      radiation field penumbra. The location of the radiation field edge is determined
      from one of these parameters. This model was tested on a group of portal images
      acquired with different conditions in our clinic. Evaluation results of this
      model and improvements in the performance of our portal image segmentation
      algorithm will be presented.

PMID- 7565386
TI  - An MR compatible flow simulator for intravascular pressure simulation.
AB  - An MR compatible flow simulator is described which generates physiologically
      realistic pressure and flow waveforms. The simulator is based on a servomotor
      driven gear pump which produces pulsatile flow by modulation of the servomotor
      rotation rate. Operation of the simulator is under the control of a personal
      computer, which executes an iterative feedback loop to minimize errors between
      measured and desired pressure waveforms. The simulator is totally automatic,
      requiring only a few minutes of iteration to generate the desired pressure
      waveform. Accurate sinusoidal waveforms with frequencies up to 10 Hz have been
      generated using the simulator, with high-frequency contamination of the measured
      waveform at least 80 dB below the fundamental frequency. Aortic waveforms have
      been produced with realistic flow rates and pressure variations. The pump
      assembly is mechanically straightforward and can operate at an 8-m distance from
      the flow phantom to allow the device to be isolated from the MR magnet room.

PMID- 7565387
TI  - Ultrasound contrast-detail analysis: a comparison of low-contrast detectability
      among scanhead designs.
AB  - Contrast-detail (CD) analysis was used to compare the low-contrast detection
      capabilities of expert observers using different array-type scanhead
      technologies. Five expert observers viewed five different contrast targets to
      obtain CD curves for each scanhead. Differences in CD curves are interpreted in
      terms of the image contrast, resolution, and noise. It was found that differences
      in low-contrast detectability were due to differences in beam properties.
      Clinical images obtained during patient examinations are used to show how some
      clinically relevant tasks are distributed in their contrast and size.

PMID- 7565388
TI  - A modeling approach for quantifying tumor hypoxia with [F-18]fluoromisonidazole
      PET time-activity data.
AB  - [F-18]fluoromisonidazole (FMISO), a positron-emitting nitroimidazole, binds
      preferentially to hypoxic cells. It has been used to image hypoxia in human
      tumors with positron emission tomography (PET). In order to quantify tumor
      oxygenation status from these PET data, a kinetic model of FMISO cellular
      bioreduction has been developed to relate cellular oxygen concentration to the
      cellular FMISO reaction rate constant, kappa A. Also, a compartmental model of
      FMISO transport and metabolism has been developed to compute the volume average
      kappa A in tissue regions from [F-18]FMISO PET time-activity data. This
      compartmental model was characterized using Monte Carlo simulations and [F
      18]FMISO PET time-activity data. The model performed well in Monte Carlo
      simulations; performance was enhanced by fixing three of the seven model
      parameters at physiologically reasonable values. The four parameters optimized
      were blood flow rate, kappa A for two partial volume/spillover correction
      factors. The model was able to accurately determine kappa A for a variety of
      computer-generated time-activity curv including those for hypothetical
      heterogeneous tissue regions and poorly perfused tissue regions. The model was
      also able to fit [H-3]FMISO time-activity data from 36B-10 rat tumors as well as
      [F-18]FMISO PET time-activity data from a human patient with a base of the tongue
      squamous cell carcinoma. The kappa A values in muscles ROIs were comparable to
      those in well-oxygenated cell monolayers while kappa A values in tumor ROIs were
      greater, suggesting the presence of hypoxic cells in the tumor.

PMID- 7565389
TI  - Simultaneous optimization of dynamic multileaf collimation and scanning patterns
      or compensation filters using a generalized pencil beam algorithm.
AB  - A very flexible iterative method for simultaneous optimization of dynamic
      multileaf collimation, scanning patterns and compensation filters has been
      developed. The algorithm can account for and optimize almost all the degrees of
      freedom available in a modern radiation therapy clinic. The method has been
      implemented for three dimensional treatment planning. The algorithm has been
      tested for a number of cases where both traditional wedge filters and block
      collimators, and modern equipment such as scanned beams and multileaf collimators
      are available. It is shown that the algorithm can improve heavily on traditional
      uniform dose plans with respect to the probability of achieving tumor control
      without causing severe complications (P+) simply by finding the optimal beam
      weights and block collimator settings. By allowing more complex equipment to
      deliver the dose and by accounting for their increased flexibility during the
      optimization, the dose plan can be substantially improved with respect to the
      applied objective functions. It is demonstrated that flexible lateral collimation
      combined with compensators or scanned beams in most cases allow close to optimal
      dose delivery. Here both the calculation time and the amount of primary computer
      memory needed has been reduced by performing the dose calculations in a cone beam
      coordinate system allowing the use of approximately spatially invariant energy
      deposition kernels. A typical calculation time for optimization of a two-field
      technique in a three dimensional volume is about 20 s per iteration step on a
      Hewlett-Packard 735 workstation. A well converged solution is normally obtained
      within about 50-100 iterations or within 15-30 min.

PMID- 7565390
TI  - Photon dose calculation incorporating explicit electron transport.
AB  - Significant advances have been made in recent years to improve photon dose
      calculation. However, accurate prediction of dose perturbation effects near the
      interfaces of different media, where charged particle equilibrium is not
      established, remain unsolved. Furthermore, changes in atomic number, which affect
      the multiple Coulomb scattering of the secondary electrons, are not accounted for
      by current photon dose calculation algorithms. As local interface effects are
      mainly due to the perturbation of secondary electrons, a photon-electron cascade
      model is proposed which incorporates explicit electron transport in the
      calculation of the primary photon dose component in heterogeneous media. The
      primary photon beam is treated as the source of many electron pencil beams. The
      latter are transported using the Fermi-Eyges theory. The scattered photon dose
      contribution is calculated with the dose spread array [T.R. Mackie, J.W.
      Scrimger, and J.J. Battista, Med. Phys. 12, 188-196 (1985)] approach. Comparisons
      of the calculation with Monte Carlo simulation and TLD measurements show good
      agreement for positions near the polystyrene-aluminum interfaces.

PMID- 7565391
TI  - Lateral electron equilibrium and electron contamination in measurements of head
      scatter factors using miniphantoms and brass caps.
AB  - The head-scatter factor (Sh) can be measured with a narrow miniphantom or a metal
      cap provided it is completely covered by the photon beam and its lateral size is
      thick enough to prevent electron contamination contributions. The effects of
      lateral electron equilibrium (LEE) and electron contamination on the Sh values
      were studied. The EGS4 Monte Carlo technique was used to calculate the minimum
      beam radii (rLEE) required to achieve complete LEE for photon beams ranging from
      60Co to 24 MV. The measurement shows that the error introduced to the Sh value
      due to lateral electron disequilibrium is negligible. The radii of the
      miniphantoms or the sidewall thicknesses of the caps can be reduced below rLEE
      provided they are thick enough to prevent the effect of electron contamination.

PMID- 7565392
TI  - Confirmation of target localization and dosimetry for 3D conformal radiotherapy
      treatment planning by MR imaging of a ferrous sulfate gel head phantom.
AB  - A detailed methodology has been developed to verify the three-dimensional (3D)
      radiation dose mapping of conformal therapy radiation treatment planning by FeMRI
      dosimetry. A phantom that consisted of a human skull filled with a 1-mM solution
      of ferrous sulfate and 0.1-N sulfuric acid gelled with 7.5% (by weight) gelatin
      was employed. With a spherical target volume in the head phantom, five
      noncoplanar conformal beams were designed through the use of a 3D treatment
      planning system developed in-house. The phantom was irradiated with a 6-MV linear
      accelerator to a total dose of 25 Gy delivered to the periphery of the target
      volume. The phantom and a set of calibration vials were scanned simultaneously in
      a GE 1.5T MR imager with six different multiscan inversion-recovery pulse
      sequences. The values of T1 were evaluated on a pixel-by-pixel basis through the
      use of custom-built software on a UNIX workstation and were converted to dose
      using calibration data. Comparisons of dose distributions between those measured
      by FeMRI and those calculated by 3D treatment planning show good agreement.

PMID- 7565393
TI  - How water equivalent are water-equivalent solid materials for output calibration
      of photon and electron beams?
AB  - The water equivalency of five "water-equivalent" solid phantom materials was
      evaluated in terms of output calibration and energy characterization over a range
      of energies for both photon (Co-60 to 24 MV) and electron (6-20 MeV) beams.
      Evaluations compared absorbed doses calculated from ionization measurements using
      the same dosimeter in the solid phantom materials and in natural water (H2O).
      Ionization measurements were taken at various calibration depths. The
      Radiological Physics Center's standard dosimetry system, a Farmer-type ion
      chamber in a water phantom, was used. Complying with the TG-21 calibration
      protocol, absorbed doses were calculated using eight measurement and
      calculational techniques for photons and five for electrons. Results of repeat
      measurements taken over a period of 2 1/2 years were reproducible to within a +/-
      0.3% spread. Results showed that various combinations of measurement techniques
      and solid phantom materials caused a spread of 3%-4% in the calculation of dose
      relative to the dose determined from measurements in water for all beam energies
      on both modalities. An energy dependence of the dose ratios was observed for both
      photons and electrons.

PMID- 7565394
TI  - Analysis of central-axis doses for high-energy x rays.
AB  - The purpose of this study was to improve on the analytical expressions used to
      describe central-axis doses for high-energy x-ray beams, in particular, the
      component due to phantom-scattered photons. The beams were characterized by
      quantities related to the physical processes, namely, transmission, head-scatter,
      and phantom-scatter factors, which were described separately with mathematical
      functions. Transmission in water was measured in a narrow beam and head scatter
      with a small phantom in air. The phantom-scatter factors, i.e., the ratios
      between total and primary dose, were deduced from measured central-axis doses per
      monitor unit. Based on previous work, it was assumed that this scatter factor is
      proportional to the depth d if the ratio between the depth and the field size s
      is constant. The proportionality constant was examined as a function of this
      ratio d/s and the effective linear attenuation coefficient mu. Two quality
      dependent parameters were extracted. One expresses the probability of scatter and
      was numerically close to mu. The other, which has not previously been studied,
      reflects the directional distribution of the scattered photons and was also found
      to be a linear function of mu. Thus the scatter factors can be estimated if mu is
      known. Central-axis doses were described by these formulas with 2.5% maximum
      error at 6 MV, 0.8% at 25 MV. To achieve this result, only a few measurements
      were needed for selected d and s, which indicates that the model used for the
      scatter factor is realistic. When the method was applied to 10-MV and 15-MV x-ray
      beam data measured by another institution, about +/- 2% accuracy resulted.

PMID- 7565395
TI  - Autoregressive-based sonogram outputs of 20 MHz pulsed Doppler data.
AB  - The sonogram outputs of autoregressive (AR) based spectral analysis of a 20 MHz
      pulsed ultrasonic Doppler blood flowmeter are presented. The data obtained from
      coronary and iliac arteries were processed using AR-based spectral analysis
      technique, and then the interpretable sonograms by the surgeons were constructed.
      When the sonogram outputs were compared to other sonograms which were analysed
      using the other techniques such as fast Fourier transform (FFT), it was observed
      that AR-based sonograms for 20 MHz pulsed Doppler data have provided better
      results. Therefore, the technique is strongly recommended in the examining of
      small vessels which are 1 to 2 mm in diameter.

PMID- 7565396
TI  - A complex cerebrovascular screening system (CERBERUS).
AB  - Stroke is unique among neurological diseases since it has a high incidence rate,
      severe burden of illness, high economic cost, and it may be preventable [1].
      Described here is a system for screening the cerebral and vascular status of
      individuals to detect the initial stages of vascular disorders. The computer
      based polygraphic system (CERBERUS) questions subjects about risk factors,
      stresses, neurologic symptoms and monitors impedance pulse waves of the head and
      extremities, EEG, and ECG. The system has been tested in 691 cases. Doppler
      control studies were carried out on approximately 300 of these cases. Additional
      somatic measures and psychological tests related to stroke risk factors were
      carried out for wide biological basis of possible correlation of CERBERUS data
      base. The high incidence of cerebrovascular disturbance was established by
      CERBERUS data, further confirmed by additional data gathered, and moreover was
      compared by traditional medical records. The polygraphic system is more sensitive
      at detecting physiological asymmetries of blood flow than even a Doppler
      measurements. This suggests that it may be a significantly improved means for the
      differential diagnosis of neurological disease and the screening of subjects for
      arteriosclerosis, transient ischemic attack and stroke prevention to be offered
      at the lowest level of medical service.

PMID- 7565397
TI  - Optimization of the power targeted to the frequency region of maximum tactile
      sensitivity.
AB  - Tactile stimulation is a means of transferring information to visually
      handicapped individuals. A study of the power delivered by the driving waveform
      to a transducer used for tactile stimulation as a function of the parameters of
      the waveform is presented. The power delivered within the region of maximum
      tactile skin sensitivity, Qfw, is compared to the total power delivered by the
      waveform in one cycle, PT, as a function of the waveform parameters with the
      objective of finding the parameters that would maximize the ratio Qfw/PT. In this
      study, the driving waveform is composed of an excitatory period followed by a
      recovery time. The excitatory period is formed by a burst of rectangular pulses
      modulated in amplitude by different waveforms. After a Fourier decomposition of
      the excitatory waveform, the contribution of each harmonic was added to compute
      the power delivered within the frequency region of interest. Additionally, to
      take in account the contribution of each harmonic in the overall tactile
      sensation, the power delivered within the region of maximum tactile skin
      sensitivity was weighed by the skin tactile sensitivity function and then
      linearly summed. The results show that the ratio Qfw/PT has a maximum for pulse
      widths between 0.8 and 1.2 ms for all pulse frequencies in the range 50-700 Hz
      when the tactile sensitivity function was not considered. The optimum pulse
      width, when the tactile sensitivity weighing function is considered in the
      computations, was in the range between 0.7 and 1.7 ms for pulse frequencies
      between 50-700 Hz. The ratio Qfw/PT is invariant to changes in the number of
      pulses per burst and the length of the recovery time. Once the tactile system
      frequency response is identified, all the waveform parameters can be specified
      for maximum power targeted to the region of maximum tactile sensitivity.

PMID- 7565398
TI  - Simple neuro-mechanical measure of the locomotor skill: an example of backward
      somersault.
AB  - We have studied skilled human locomotions in sports gymnastics by measurement and
      analysis of ground reaction force and myoelectric signals. Assuming the quality
      of performance to be a skill level criterion acquired signals were mathematically
      analyzed via basic signal processing and cross-correlation methods. The study of
      backward somersault yielded quantitative criteria of performance, proposing an
      original measure-an inter-muscular cross-correlation function. Besides motor
      learning, the quantification of movement skill introduced here also relates to
      possible applications in biocybernetics, robotics and rehabilitation medicine.

PMID- 7565399
TI  - A retrospective analysis of 6,387 cholecystectomies.
AB  - This is the largest retrospective analysis of biliary tract surgery ever reported
      involving 6,378 patients operated on during a three year period, 1990-1992.
      During this time interval, the frequency of laparoscopic procedures has increased
      dramatically. The use of laparoscopic procedures was associated with a
      significant decrease in the total length of hospital stay and total charges as
      compared to the open procedures. Because of laparoscopic surgery's increased
      acceptance, we propose that the frequency of laparoscopic surgery of the biliary
      tract should be used as a quality control measure.

PMID- 7565400
TI  - Development of a ferrocene-mediated needle-type glucose sensor covered with newly
      designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n
      butyl methacrylate.
AB  - To prepare the long-life and stable glucose sensor, we developed the ferrocene
      mediated needle-type glucose sensor covered with newly designed biocompatible
      membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate (MPC
      co-BMA) membrane. In this membrane, the hydrophilic phosphorylcholine chains were
      grafted on the hydrophobic polymer surface. 1. The poly(MPC-co-BMA) membrane
      inhibited platelet activation and protein adhesion on the surface, showing
      excellent biocompatibility. These results suggested that the hydrophilic
      phospholipids chains might have the potential for suppressing activation and
      adsorption of biochemical molecules. 2. The ferrocene-mediated needle-type
      glucose sensor covered with poly(MPC-co-BMA) membrane achieved excellent results
      in vitro. Subcutaneous tissue glucose concentrations were measured in a wide
      range from 1.7 to more than 16.7 mmol/l. The correlation between subcutaneous
      tissue (Y) and blood (X) glucose concentrations was Y = 1.04X + 0.12 (r = 0.98).
      The subcutaneous tissue glucose concentrations could be monitored precisely for 7
      days without any in vivo calibrations, and for 14 days by introducing in vivo
      calibrations. We therefore conclude that this sensor is stable and reliable, as
      compared to any other glucose sensors we developed.

PMID- 7565401
TI  - [Neuropsychiatric performance of HIV-infected patients].
AB  - AIM: Can neuropsychic impairment which is clinically observed in the case of HIV
      infected patients be objectivized, and what is the relationship to somatic
      features caused by the disease? PATIENTS AND METHOD: 65 HIV-infected men with no
      history of drug-addiction were examined by means of a test battery which
      monitored the functions memory/concentration and speed of response. The probands
      were then compared to a healthy control group which was parallelized with respect
      to age, sex and education. Immune status, HIV and AIDS associated symptoms as
      well as educational diseases were checked for their connection with neuropsychic
      impairment. RESULTS: Compared to healthy persons HIV patients presented
      significant deficits with respect to memory and concentration but showed no
      reduction of speed of response. Significant correlation could be determined with
      only one somatic feature: Half of the patients who had lost more than 10% of
      their body weight during the preceding three months suffered from clinically
      relevant memory and concentration disorders. CONCLUSIONS: 1. The massive memory
      and concentration disorders impair and isolate the patients and can have
      considerable job-related consequences. 2. Measures preventing loss of weight
      should be initiated as early as possible. 3. Training sessions, e.g. nutritional
      consultation, must take the patients' deficits with respect to concentration and
      memory into consideration. 4. Possible connections between loss of weight and
      changes in brain metabolism should be examined. 5. Future studies should
      determine whether measures weight increase coincide with an improvement of memory
      and concentration.

PMID- 7565402
TI  - [Scintigraphy of the parathyroid glands with 99mTc-MIBI].
AB  - AIM: Since about 3 years 99mTc-MIBI is used instead of 201Tl/99mTc subtraction
      scintigraphy for the localization of parathyroid involvement in
      hyperparathyroidism (HPT). The sensitivity of the new method was evaluated.
      PATIENTS AND METHODS: 24 patients aged between 28 and 83 years with surgically
      confirmed primary HPT were studied. Planar images were acquired 15 minutes and 3
      hours after tracer injection. Additionally, in 9 patients dynamic images were
      obtained for 2 hours to study tracer kinetics. RESULTS: 19 out of 24 adenomas
      (79%) were identified correctly with 99mTc-MIBI. CONCLUSION: The sensitivity of
      the scintigraphy using 99mTc-MIBI is in the range of the 201Tl/99mTc subtraction
      scintigraphy. Because of the superior logistic and the lower radiation exposure,
      99mTc-MIBI can replace the 201Tl/99mTc scintigraphy in the preoperative
      diagnostic assessment.

PMID- 7565404
TI  - [A patient with multiple endocrine tumors].

PMID- 7565405
TI  - [Angiology update].

PMID- 7565403
TI  - [Acute liver failure as the initial manifestation of Wilson disease].
AB  - BACKGROUND: Establishing an early diagnosis is crucial to successfully treat
      mostly young patients with sudden onset acute hepatic failure as the initial
      symptom of Wilson's disease. Recognition of the entity of Wilsonian fulminant
      hepatitis is important, because liver transplantation improves survival if
      performed in a timely fashion. METHODS: Retrospective case analysis regarding
      characteristic profile of standard laboratory parameters and clinical course of
      acute Wilsonian hepatic failure. RESULTS: In two female patients (age 17 and 27
      years) with non-autoimmune hemolysis serum AST and ALT levels were only
      moderately elevated with a conspicuously diminished ALT activity and relatively
      low serum alkaline phosphatase (AP) levels. Despite immediate application of D
      Penicillamin one patient died from complications of multiorgan failure.
      CONCLUSION: In fulminant Wilsonian hepatic failure the AP/bilirubin ratio is
      usually below 2. Additionally calculation of free copper concentration in serum
      and renal excretion of ionic copper in combination with non-autoimmune hemolysis
      provide clues to establish an early diagnosis of Wilsonian hepatic failure.

PMID- 7565406
TI  - [Sleep-related apnea disorders and associated cardiovascular diseases].

PMID- 7565407
TI  - [Prevention and therapy of nutrition-induced diseases and disease-induced
      nutrition disorders by internists. Deficiencies and future developments].

PMID- 7565408
TI  - [Excessive diurnal fatigue with psychotic symptoms in Pickwickian syndrome].

PMID- 7565409
TI  - Protein trafficking in kinetoplastid protozoa.
AB  - The kinetoplastid protozoa infect hosts ranging from invertebrates to plants and
      mammals, causing diseases of medical and economic importance. They are the
      earliest-branching organisms in eucaryotic evolution to have either mitochondria
      or peroxisome-like microbodies. Investigation of their protein trafficking
      enables us to identify characteristics that have been conserved throughout
      eucaryotic evolution and also reveals how far variations, or alternative
      mechanisms, are possible. Protein trafficking in kinetoplastids is in many
      respects similar to that in higher eucaryotes, including mammals and yeasts.
      Differences in signal sequence specificities exist, however, for all subcellular
      locations so far examined in detail--microbodies, mitochondria, and endoplasmic
      reticulum--with signals being more degenerate, or shorter, than those of their
      higher eucaryotic counterparts. Some components of the normal array of
      trafficking mechanisms may be missing in most (if not all) kinetoplastids:
      examples are clathrin-coated vesicles, recycling receptors, and mannose 6
      phosphate-mediated lysosomal targeting. Other aspects and structures are unique
      to the kinetoplastids or are as yet unexplained. Some of these peculiarities may
      eventually prove to be weak points that can be used as targets for chemotherapy;
      others may turn out to be much more widespread than currently suspected.

PMID- 7565411
TI  - Immune regulation in Epstein-Barr virus-associated diseases.
AB  - Epstein-Barr virus (EBV) is a member of the human herpesvirus family and, like
      many other herpesviruses, maintains a lifelong latent association with B
      lymphocytes and a permissive association with stratified epithelium in the
      oropharynx. Clinical manifestations of primary EBV infection range from acute
      infectious mononucleosis to an asymptomatic persistent infection. EBV is also
      associated with a number of malignancies in humans. This review discusses
      features of the biology of the virus, both in cell culture systems and in the
      natural host, before turning to the role of the immune system in controlling EBV
      infection in healthy individuals and in individuals with EBV-associated diseases.
      Cytotoxic T cells that recognize virally determined epitopes on infected cells
      make up the major effector arm and control the persistent infection. In contrast,
      the options for immune control of EBV-associated malignancies are more
      restricted. Not only is antigen expression restricted to a single nuclear
      antigen, EBNA1, but also these tumor cells are unable to process EBV latent
      antigens, presumably because of a transcriptional defect in antigen-processing
      genes (such as TAP1 and TAP2). The likelihood of producing a vaccine capable of
      controlling the acute viral infection and EBV-associated malignancies is also
      discussed.

PMID- 7565412
TI  - Fungal lipopeptide mating pheromones: a model system for the study of protein
      prenylation.
AB  - In a variety of fungal species, mating between haploid cells is initiated by the
      action of peptide pheromones. The identification and characterization of several
      fungal pheromones has revealed that they have common structural features
      classifying them as lipopeptides. In the course of biosynthesis, these pheromones
      undergo a series of posttranslational processing events prior to export. One
      common modification is the attachment of an isoprenoid group to the C terminus of
      the pheromone precursor. Genetic and biochemical investigations of this
      biosynthetic pathway have led to the elucidation of genes and enzymes which are
      responsible for isoprenylation of other polypeptides including the nuclear
      lamins, several vesicular transport proteins, and the oncogene product Ras. The
      alpha-factor of Saccharomyces cerevisiae serves as a model for studying the
      biosynthesis, export, and bioactivity of lipopeptide pheromones. In addition to
      being isoprenylated with a farnesyl group, the alpha-factor is secreted by a
      novel peptide export pathway utilizing a yeast homolog of the mammalian multidrug
      resistance P-glycoprotein. The identification of putative lipopeptide-encoding
      loci within other fungi, including the human immunodeficiency virus-associated
      opportunistic pathogen Cryptococcus neoformans and the plant pathogen Ustilago
      maydis, has stimulated much interest in understanding possible roles for
      pheromones in fungal proliferation and pathogenicity. Knowledge of variations
      within the processing, export, and receptor-mediated signal transduction pathways
      associated with different fungal lipopeptide pheromones will continue to provide
      insights into similar mechanisms which exist in higher eukaryotes.

PMID- 7565417
TI  - Anesthesia in Che'diak-Higashi syndrome--case report.
AB  - Che'diak-Higashi syndrome (CHS) is a lethal, progressive, autosomal recessive,
      systemic disorder associated with oculocutaneous albinism, photopobia, nystagmus,
      massive leukocyte inclusions (giant lysosomes), histiocytic infiltration of
      multiple body organs, development of pancytopenia, hepatosplenomegaly, recurrent
      or persistent bacterial infections, and a possible predisposition to development
      of malignant lymphoma. This rare disorder of children characterized by impaired
      resistance to bacterial infection leading to early demise. This syndrome is
      rarely seen. We are presenting this case report to discuss a patient with
      Che'diak-Higashi syndrome, who was scheduled for splenectomy in our clinic.

PMID- 7565418
TI  - Airway protection by the laryngeal mask airway in children.
AB  - The pediatric laryngeal mask airway (LMA) is a scale-down version of the adult
      form, and no direct postmortem specimen work has been performed so far. There are
      several anatomical differences between pediatric and adult airways, and hence,
      the scale-down version of the adult LMA is not necessarily water-tight in
      pediatric patients. We performed a prospective study to assess airway protection
      by the LMA in pediatric patients, using methylence blue (injected in the pharynx
      outside the LMA) and the fibreoptic bronchoscope to view the inside of the mask,
      to detect any leakage of the dye. Fifty Patients (40 boys and 10 girls) aged 1-10
      years (mean 4.5 yr) were studied. All patients underwent surgery below the level
      of the umbilicus, under light general anesthesia combined with caudal epidural
      block. All patients were allowed to breath spontaneously over an Ayre's T-piece.
      Dye staining of the inside of the mask was detected in 5 patients (10%). The
      esophageal opening was visualized within the mask in 3 patients (6%). No serious
      complications occurred in any of our patients.

PMID- 7565410
TI  - Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.
AB  - In fungi and many other organisms, a thick outer cell wall is responsible for
      determining the shape of the cell and for maintaining its integrity. The budding
      yeast Saccharomyces cerevisiae has been a useful model organism for the study of
      cell wall synthesis, and over the past few decades, many aspects of the
      composition, structure, and enzymology of the cell wall have been elucidated. The
      cell wall of budding yeasts is a complex and dynamic structure; its arrangement
      alters as the cell grows, and its composition changes in response to different
      environmental conditions and at different times during the yeast life cycle. In
      the past few years, we have witnessed a profilic genetic and molecular
      characterization of some key aspects of cell wall polymer synthesis and
      hydrolysis in the budding yeast. Furthermore, this organism has been the target
      of numerous recent studies on the topic of morphogenesis, which have had an
      enormous impact on our understanding of the intracellular events that participate
      in directed cell wall synthesis. A number of components that direct polarized
      secretion, including those involved in assembly and organization of the actin
      cytoskeleton, secretory pathways, and a series of novel signal transduction
      systems and regulatory components have been identified. Analysis of these
      different components has suggested pathways by which polarized secretion is
      directed and controlled. Our aim is to offer an overall view of the current
      understanding of cell wall dynamics and of the complex network that controls
      polarized growth at particular stages of the budding yeast cell cycle and life
      cycle.

PMID- 7565420
TI  - Factors affecting drug metabolism in critically ill patients.

PMID- 7565421
TI  - Total intravenous anesthesia--a pharmacokinetic approach.

PMID- 7565419
TI  - Evaluation of different induction techniques for tracheal intubation.
AB  - Conditions for tracheal intubation and the hemodynamic changes associated with
      different intravenous anesthetic induction techniques were studied in seventy-two
      ASA I patients randomly assigned to one of six groups (G). Anesthesia was induced
      with I.V. propofol 2.5 in G 1, 3, 5 or with thiopental 5 mg/kg (G2, 4, 6). In G 1
      4, the standard sequence of administering muscle relaxant was used. G 1 and 2
      received succinylcholine 1 mg/kg after induction, and one min later laryngoscopy
      and orotracheal intubation attempted. G3 and 4 received 0.5 mg/kg atracurium and
      intubation attempted 3 min later. In G 5 and G 6 the "timing principle" was used;
      atracurium 0.5 mg/kg was given first followed by propofol and thiopental, and one
      minute after the induction agent intubation attempted. There was no statistically
      significant difference in the intubating conditions between the six groups of
      patients studied. Similar to succinylcholine timing technique with atracurium and
      propofol or thiopental reliably provided excellent or good intubating conditions
      in two minutes.

PMID- 7565422
TI  - Brain-stem auditory evoked potentials study during isoflurane-N2O anesthesia--a
      measure of depth of anesthesia.

PMID- 7565414
TI  - Molecular biology of microbial ureases.
AB  - Urease (urea amidohydrolase; EC 3.5.1.5) catalyzes the hydrolysis of urea to
      yield ammonia and carbamate. The latter compound spontaneously decomposes to
      yield another molecule of ammonia and carbonic acid. The urease phenotype is
      widely distributed across the bacterial kingdom, and the gene clusters encoding
      this enzyme have been cloned from numerous bacterial species. The complete
      nucleotide sequence, ranging from 5.15 to 6.45 kb, has been determined for five
      species including Bacillus sp. strain TB-90, Klebsiella aerogenes, Proteus
      mirabilis, Helicobacter pylori, and Yersinia enterocolitica. Sequences for
      selected genes have been determined for at least 10 other bacterial species and
      the jack bean enzyme. Urease synthesis can be nitrogen regulated, urea inducible,
      or constitutive. The crystal structure of the K. aerogenes enzyme has been
      determined. When combined with chemical modification studies, biophysical and
      spectroscopic analyses, site-directed mutagenesis results, and kinetic inhibition
      experiments, the structure provides important insight into the mechanism of
      catalysis. Synthesis of active enzyme requires incorporation of both carbon
      dioxide and nickel ions into the protein. Accessory genes have been shown to be
      required for activation of urease apoprotein, and roles for the accessory
      proteins in metallocenter assembly have been proposed. Urease is central to the
      virulence of P. mirabilis and H. pylori. Urea hydrolysis by P. mirabilis in the
      urinary tract leads directly to urolithiasis (stone formation) and contributes to
      the development of acute pyelonephritis. The urease of H. pylori is necessary for
      colonization of the gastric mucosa in experimental animal models of gastritis and
      serves as the major antigen and diagnostic marker for gastritis and peptic ulcer
      disease in humans. In addition, the urease of Y. enterocolitica has been
      implicated as an arthritogenic factor in the development of infection-induced
      reactive arthritis. The significant progress in our understanding of the
      molecular biology of microbial ureases is reviewed.

PMID- 7565423
TI  - Low dose epidural lidocaine/sufentanil is effective for outpatient lithotripsy.
AB  - Lumbar epidural analgesia was administered to 60 ASA class 1 & 2 patients with 3
      ml test dose of 1.5% lidocaine and bolus of 20 ml of 0.5% lidocaine containing
      0.5 microgram/kg sufentanil. Bilateral decreased lumbar cold perception was
      accepted as evidence of analgesia despite persisting pinprick sensation in
      thoracic dermatomes. Oxygen saturation (SpO2), respiratory rate, cardiovascular
      parameters and leg muscle strength were monitored throughout and until 1 hour
      afterwards. Midazolam provided light sedation and atropine bradycardia control.
      Verbal communication was maintained. ESWL could start within 6-10 minutes of
      bolus, with analgesia adequate in 86% of patients, the rest being "rescued" with
      5-10 ml 0.5% lidocaine or analgesic doses (20-30 mg IV) of ketamine. Leg weakness
      developed in 14%, with 1 patient fully paralyzed. All resolved within 1 hour.
      Topical urethral analgesia was used in males where cystoscopy preceded ESWL.
      Phenylephrine was required once for nild systolic hypotension, otherwise blood
      pressures were stable. Two of 4 patients experiencing pruritus needed naloxone
      relief. Itching appeared in skin recovering from sensory block while visceral
      analgesia persists. Excessive respiratory depression was not seen.

PMID- 7565424
TI  - Changes of haptoglobin and free hemoglobin due to blood transfusion.
AB  - Serum total haptoglobin and free hemoglobin levels during blood transfusion were
      investigated in 17 elective surgeries. Total haptoglobin and free hemoglobin
      levels in 73 stored whole blood were also investigated for different storage
      periods. Free hemoglobin was detected in serum when total haptoglobin level
      became 130 mg/dl or less and a mean storage period of transfused bloods were 11
      days or longer. Total haptoglobin level became 130 mg/dl or less at a transfusion
      volume of 600 ml or more. No constant relationship was recognized between
      transfusion speed and total haptoglobin or free hemoglobin levels. In the stored
      whole blood, free hemoglobin level increased in accordance with an increase of
      storage period and it reached significant increase on 7-9 storage period against
      1-3 storage period. The detection rate of free hemoglobin increased significantly
      when it was stored for 7 days or longer. It was concluded that 7 days or more
      stored whole bloods had free hemoglobin, but serum free hemoglobin was detected
      when 600ml or more of 11 days or longer whole bloods were transfused.

PMID- 7565425
TI  - Nifedipine versus fentanyl to prevent the pressor response to tracheal
      intubation.
AB  - Thirty six patients ASA 1 or 2, undergoing surgery that required tracheal
      intubation, were allocated randomly into three groups of twelve each. Before
      induction of anesthesia, they received either saline, 10 mg, nifedipine
      sublingual, or fentanyl 1.5 micrograms.kg-1 IV. Heart rate (HR), systolic blood
      pressure (SAP), diastolic blood pressure (DBP), and mean blood pressure (MAP),
      were recorded automatically every minute for 5 minutes before induction of
      anesthesia, and for 5 minutes after intubation. Nifedipine was better than
      fentanyl in blocking the pressor response. The fentanyl dose was too small to
      abolish this response completely. The increase in HR and blood pressure were most
      evident in the control group, followed by fentanyl, and the least increase was
      seen with nifedipine.

PMID- 7565427
TI  - Relative hypoparathyroidism in hemodialysis patients.
AB  - To clarify the incidence and contributing factors of hypoparathyroidism in a
      hemodialysis (HD) population, 224 patients undergoing maintenance HD were
      investigated. They were divided into 4 groups according to their high-sensitive
      parathyroid hormone levels: extra-high (EH) group > 420,000 pg/ml; high (H) group
      20,000-420,000 pg/ml; moderate (M) group 4,500-20,000 pg/ml; low (L) group, <
      4,500 pg/ml. In group L, a 25-mg/kg deferoxamine (DFO) infusion test was
      undertaken to estimate aluminum (Al) accumulation. The distribution in each group
      was 42, 35, 12, and 11% for groups L, M, H and EH, respectively. Group-L patients
      were relatively older than those of the other groups. Diabetes was seen in 20% of
      group-L patients, as opposed to no diabetes in groups H and EH. Among the 22
      diabetics, 82% were in group L. 70% of group-L patients showed a less than 50
      micrograms/l Al increment after the DFO infusion test. Bone mineral density (BMD)
      did not differ between the groups with relative hypoparathyroidism (RHP=L) and
      background-matched non-RHP, either at the initiation of HD or the recent period,
      and the changes in BMD were comparable between the 2 groups. These results
      suggest that a considerable number of HD patients show RHP. Diabetes, but not Al
      accumulation, was considered to be one of the predisposing factors of RHP. Though
      the outcome of RHP will be aplastic bone disease (ABD) in HD patients, the
      clinical significance of ABD has not been fully evaluated. Further studies are
      required to clarify the precise mechanisms of RHP and the significance of ABD.

PMID- 7565428
TI  - Growth of parathyroid gland in uremic patients on maintenance hemodialysis.
AB  - High-resolution, real-time ultrasonography was performed in 245 uremic patients
      on maintenance hemodialysis and the growth of the enlarged parathyroid glands was
      compared with the clinical and biochemical signs during follow-up periods of 12
      months. The total volume of the parathyroid glands was significantly correlated
      with the serum C-terminal parathyroid hormone (C-PTH; r = 0.379, p = 0.0001) and
      calcium levels (r = 0.252, p = 0.0224). After 12 months, the total volume of the
      enlarged parathyroid glands and serum C-PTH or calcium levels were correlated
      more closely than in the initial study (r = 0.615, p = 0.0001, and r = 0.489, p =
      0.0002, respectively). Both the serum C-PTH levels and the total volume of the
      enlarged parathyroid glands increased significantly (p = 0.0001), while the ratio
      between the serum C-PTH levels and the volume of the parathyroid glands decreased
      significantly (p = 0.0001). There was no difference in the clinical and
      biochemical signs except for the serum aluminum levels between the patients with
      and without an increased gland volume. These results suggest that the growth of
      parathyroid glands may progress more rapidly than the increase in the serum PTH
      levels, independent of the serum calcium levels, in uremic patients on
      maintenance hemodialysis.

PMID- 7565429
TI  - Intravenous calcitriol can increase bone mass in hemodialysis patients with
      osteitis fibrosa.
AB  - Intravenous calcitriol administration (IVC) suppressed parathyroid hormone (PTH)
      secretion and improved osteitis fibrosa (OF) in long-term hemodialysis (HD)
      patients, although it did not increase the mineralized bone area or the mineral
      apposition rate. We observed the long-term effects of IVC on OF in 8 HD patients.
      Bone biopsy of 7 patients revealed increased bone turnover and decreased bone
      mass. One microgram of calcitriol was given intravenously three times weekly
      after each HD session for 12 months. The dose was adjusted to maintain the serum
      corrected calcium level at < 11.5 mg/dl. Dual-energy X-ray bone absorptiometry
      (DEXA), 3rd lumbar vertebra bone density by quantitative computed tomography
      (QCT), and biochemical data were taken before IVC, and after 6 and 12 months of
      IVC. Seven HD patients were given 0.5 microgram/day 1 alpha-cholecalcitriol as
      controls. The serum corrected calcium levels were 9.9 +/- 0.3 (mean +/- SE) and
      11.1 +/- 0.2 mg/dl at 0 and 12 months, respectively (p = 0.06). The serum
      phosphate levels were 6.2 +/- 0.7 and 6.6 +/- 0.6 mg/day at 0 and 12 months,
      respectively (p = 0.56). The serum intact PTH levels were 928 +/- 281 and 617 +/-
      192 (p = 0.016) at 0 and 12 months, respectively. The bone mass of the 3rd lumbar
      vertebra measured by QCT was 195 +/- 17 and 218 +/- 186 g/cm3 at 0 and 12 months,
      respectively (p = 0.156). The bone mass of the trunk measured by DEXA was 660 +/-
      44 and 706 +/- 32 g and 0 and 12 months, respectively (p = 0.156). These
      parameters did not change in controls. Sequential bone biopsy in 3 cases also
      supported these changes. We conclude that IVC not only suppresses bone turnover,
      but that it also restores decreased bone mass in HD patients with OF.

PMID- 7565426
TI  - Proceedings of the 3rd International Conference on New Actions of Parathyroid
      Hormone. Kyoto, Japan, April 18-24, 1994.

PMID- 7565432
TI  - Multiple sites of synthesis and action of parathyroid hormone-related protein.

PMID- 7565431
TI  - Parathyroid hormone induces sequential c-fos expression in bone cells in vivo: a
      model for intercellular communication in bone.

PMID- 7565430
TI  - Comparison of bone scans, parathyroid hormone levels and bone mineral densities
      in hemodialysis patients.
AB  - We have evaluated bone scans, parathyroid hormone (PTH) levels and bone mineral
      densities (BMDs) of hemodialysis (HD) patients. The bone scans were grouped into
      4 types (type 1-4). Type 1 showed a diffusely high activity of the tracer in the
      whole skeleton especially in the skull: secondary hyperparathyroidism pattern.
      Type 2 showed high background activity, the same pattern as osteomalacia. Type 3
      was a mixture of types 1 and 2. Type 4 was almost normal. The PTH levels of type
      1 were higher and the radius BMDs were lower than those of the other types. The
      radius BMDs in one third of type-2 patients were lower than the normal range. A
      comparison of bone scans, PTH and BMDs helps to evaluate bone changes in HD
      patients.

PMID- 7565433
TI  - Expression of parathyroid hormone-related peptide and its receptor mRNAs during
      fetal development of rats.

PMID- 7565434
TI  - The mechanisms responsible for the PTH-induced rise in cytosolic calcium in
      various cells are not uniform.

PMID- 7565416
TI  - Stress-induced transcriptional activation.
AB  - Living cells, both prokaryotic and eukaryotic, employ specific sensory and
      signalling systems to obtain and transmit information from their environment in
      order to adjust cellular metabolism, growth, and development to environmental
      alterations. Among external factors that trigger such molecular communications
      are nutrients, ions, drugs and other compounds, and physical parameters such as
      temperature and pressure. One could consider stress imposed on cells as any
      disturbance of the normal growth condition and even as any deviation from optimal
      growth circumstances. It may be worthwhile to distinguish specific and general
      stress circumstances. Reasoning from this angle, the extensively studied response
      to heat stress on the one hand is a specific response of cells challenged with
      supra-optimal temperatures. This response makes use of the sophisticated
      chaperoning mechanisms playing a role during normal protein folding and turnover.
      The response is aimed primarily at protection and repair of cellular components
      and partly at acquisition of heat tolerance. In addition, heat stress conditions
      induce a general response, in common with other metabolically adverse
      circumstances leading to physiological perturbations, such as oxidative stress or
      osmostress. Furthermore, it is obvious that limitation of essential nutrients,
      such as glucose or amino acids for yeasts, leads to such a metabolic response.
      The purpose of the general response may be to promote rapid recovery from the
      stressful condition and resumption of normal growth. This review focuses on the
      changes in gene expression that occur when cells are challenged by stress, with
      major emphasis on the transcription factors involved, their cognate promoter
      elements, and the modulation of their activity upon stress signal transduction.
      With respect to heat shock-induced changes, a wealth of information on both
      prokaryotic and eukaryotic organisms, including yeasts, is available. As far as
      the concept of the general (metabolic) stress response is concerned, major
      attention will be paid to Saccharomyces cerevisiae.

PMID- 7565436
TI  - Disruption of the parathyroid hormone-related peptide gene.

PMID- 7565435
TI  - Approaches to studying the biomolecular interaction between the parathyroid
      hormone/parathyroid hormone-related protein receptor and its ligands.

PMID- 7565437
TI  - Parathyroid hormone-related protein gene expression and human T cell leukemia
      virus-1 infection.

PMID- 7565439
TI  - Parathyroid hormone-related peptide and models of vascular disease: its
      expression and action in vascular smooth muscle cells.

PMID- 7565438
TI  - Parathyroid hormone-related peptide expression in endocrine tumors.
AB  - Parathyroid hormone-related peptide (PTHrP) expression is associated with the
      histological type in pituitary tumor, but not in thyroid carcinoma. However
      invasive and metastatic tumors showed intense PTHrP staining in both pituitary
      and thyroid tumors. Analysis of the established metastatic rat pituitary tumor
      cell line showed that PTHrP plays a crucial role in in vivo cell proliferation
      closely related to worsening of malignant transformation and neovascularization
      in a paracrine fashion.

PMID- 7565440
TI  - Role of parathyroid hormone-related protein in the proliferation of vascular
      smooth muscle cells.
AB  - Human parathyroid hormone-related protein(1-34) [hPTHrP(1-34)] inhibited
      [3H]thymidine incorporation into DNA of cultured vascular smooth muscle cells
      (VSMC) and increased intracellular cAMP accumulation, both in a concentration
      dependent manner. The potency of hPTHrP(1-34) was similar to that of human
      parathyroid hormone(1-34) [hPTH(1-34)], but their antagonists, hPTHrP(7-34) and
      hPTH(3-34), showed no effect on VSMC DNA synthesis. The inhibitory effect of
      PTHrP on VSMC DNA synthesis was mimicked by dibutyryl-cAMP but not by dibutyryl
      cGMP. These results suggest that PTHrP, as an autocrine and/or paracrine
      regulator, may inhibit VSMC DNA synthesis mediated at least partly by cAMP, a
      second messenger which has also been proposed to mediate vascular relaxation.

PMID- 7565413
TI  - mRNA stability in mammalian cells.
AB  - This review concerns how cytoplasmic mRNA half-lives are regulated and how mRNA
      decay rates influence gene expression. mRNA stability influences gene expression
      in virtually all organisms, from bacteria to mammals, and the abundance of a
      particular mRNA can fluctuate manyfold following a change in the mRNA half-life,
      without any change in transcription. The processes that regulate mRNA half-lives
      can, in turn, affect how cells grow, differentiate, and respond to their
      environment. Three major questions are addressed. Which sequences in mRNAs
      determine their half-lives? Which enzymes degrade mRNAs? Which (trans-acting)
      factors regulate mRNA stability, and how do they function? The following specific
      topics are discussed: techniques for measuring eukaryotic mRNA stability and for
      calculating decay constants, mRNA decay pathways, mRNases, proteins that bind to
      sequences shared among many mRNAs [like poly(A)- and AU-rich-binding proteins]
      and proteins that bind to specific mRNAs (like the c-myc coding-region
      determinant-binding protein), how environmental factors like hormones and growth
      factors affect mRNA stability, and how translation and mRNA stability are linked.
      Some perspectives and predictions for future research directions are summarized
      at the end.

PMID- 7565441
TI  - Signal transduction mechanisms of parathyroid hormone- and parathyroid hormone
      related-peptide-stimulated osteoclast-like cell formation from hemopoietic blast
      cells.

PMID- 7565442
TI  - Parathyroid hormone-related peptide in hypercalcemia associated with adult T cell
      leukemia/lymphoma: molecular and cellular mechanism of parathyroid hormone
      related peptide overexpression in HTLV-I-infected T cells.

PMID- 7565443
TI  - A case of acute lymphoblastic leukemia accompanied with the production of
      parathyroid hormone-related protein.
AB  - Hypercalcemia accompanied with malignant tumors is generally classified into two
      categories, namely with or without bone metastasis. As for the latter, bone
      resorption-stimulating factors produced by tumor cells, such as parathyroid
      hormone-related protein (PTHrP), show hormone-like effects and promote a bone
      resorption. Many cases have been reported regarding the production of TPTHrP in
      adult T cell leukemia (ATL), but few have been reported with acute lymphoblastic
      leukemia (ALL). We report here a similar case with ALL. A 12-year-old male
      presented with fever, petechiae and thrombocytopenia, and was diagnosed as ALL.
      We started the induction therapy and confirmed complete remission. Later, he
      relapsed 3 times without symptoms apart from hypercalcemia at the beginning.
      Elevation of the serum calcium level followed by a rise of lymphoblastic cells
      was recognized. Bone metastasis was excluded since bone mineral density and serum
      mid region PTH were normal and no abnormal findings were noticed on X rays and
      99mTc bone scintigraphy. However, his urinary PTHrP level was high, and his
      lymphoblastic cells staining immunocytochemically with the monoclonal antibodies
      against the C-terminal region of PTHrP showed a positively brownish color.
      Finally, he died of pulmonary aspergillosis. Hypercalcemia was not related to
      serum PTH or bone metastasis. ATL viral infection reported as a cause of PTHrP
      production was also excluded from several experimental data. Therefore, we
      concluded that lymphoblastic cells directly produced PTHrP, and that this PTHrP
      played an important role in the induction of hypercalcemia.

PMID- 7565444
TI  - Structural requirements of parathyroid hormone/parathyroid hormone-related
      peptide receptors for phospholipase C activation and regulation of phosphate
      uptake.

PMID- 7565415
TI  - Regulation of human immunodeficiency virus type 1 and cytokine gene expression in
      myeloid cells by NF-kappa B/Rel transcription factors.
AB  - CD4+ macrophages in tissues such as lung, skin, and lymph nodes, promyelocytic
      cells in bone marrow, and peripheral blood monocytes serve as important targets
      and reservoirs for human immunodeficiency virus type 1 (HIV-1) replication. HIV-1
      infected myeloid cells are often diminished in their ability to participate in
      chemotaxis, phagocytosis, and intracellular killing. HIV-1 infection of myeloid
      cells can lead to the expression of surface receptors associated with cellular
      activation and/or differentiation that increase the responsiveness of these cells
      to cytokines secreted by neighboring cells as well as to bacteria or other
      pathogens. Enhancement of HIV-1 replication is related in part to increased DNA
      binding activity of cellular transcription factors such as NF-kappa B. NF-kappa B
      binds to the HIV-1 enhancer region of the long terminal repeat and contributes to
      the inducibility of HIV-1 gene expression in response to multiple activating
      agents. Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B
      alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding
      activity. Both N- and C-terminal residues of I kappa B alpha are required for
      inducer-mediated degradation. Chronic HIV-1 infection of myeloid cells leads to
      constitutive NF-kappa B DNA-binding activity and provides an intranuclear
      environment capable of perpetuating HIV-1 replication. Increased intracellular
      stores of latent NF-kappa B may also result in rapid inducibility of NF-kappa B
      dependent cytokine gene expression. In response to secondary pathogenic
      infections or antigenic challenge, cytokine gene expression is rapidly induced,
      enhanced, and sustained over prolonged periods in HIV-1-infected myeloid cells
      compared with uninfected cells. Elevated levels of several inflammatory cytokines
      have been detected in the sera of HIV-1-infected individuals. Secretion of
      myeloid cell-derived cytokines may both increase virus production and contribute
      to AIDS-associated disorders.

PMID- 7565445
TI  - Effects of C-terminal parathyroid hormone-related peptide on osteoblasts.
AB  - A C-terminal analog of parathyroid hormone-related peptide (PTHrP), PTHrP(107
      139), was found to stimulate cAMP production in three osteoblast cell
      preparations. The effect was studied most extensively in ROS 17/2.8 cells. The
      effect was dose-related and comparable in magnitude to that produced by PTHrP(1
      34), but potency was lower. The functional significance of the cAMP effect is
      unknown, but preliminary findings indicated that PTHrP(107-139) also inhibited
      osteopontin mRNA levels in ROS 17/2.8 cells treated with peptide for 48 h. The
      results suggest that the carboxy-terminal region of PTHrP may play a role in bone
      metabolism by influencing osteoblast activity.

PMID- 7565446
TI  - PTH-mediated osteoblast retraction: possible participation of the calpain
      pathway.
AB  - Parathyroid hormone (PTH)-induced osteoblast retraction may play a pivotal role a
      role in bone resorption by providing osteoclasts direct access to mineralized
      bone surface. We have been working on the hypothesis that the calpains
      participate in this retractile response through a calcium-dependent process. We
      have first demonstrated the presence of calpain activities in MC3T3-E1
      osteoblastic cells and that these activities can be stimulated by PTH. Second, we
      have demonstrated that the PTH-induced osteoblast retraction is dramatically
      attenuated by two different cysteine protease inhibitors. Finally, initial
      immunofluorescent cytochemical studies suggest that this PTH-induced osteoblastic
      retraction is mediated through a calpain-dependent, proteolytic modification of
      the cytoskeletal organization.

PMID- 7565449
TI  - Involvement of polyamines in the proliferation of bovine parathyroid cells.
AB  - An active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is involved
      in the regulation of parathyroid cell proliferation as well as of parathyroid
      hormone synthesis. We examined the effects of 1,25-(OH)2D3 on the proliferation
      of parathyroid cells in relation to their effects on ornithine decarboxylase
      (ODC) activity. Exposure of bovine parathyroid cells to serum caused an elevation
      in [3H]thymidine incorporation, which was preceded by a rise in ODC activity. The
      biodegradative enzyme, spermidine/spermine N1-acetyltransferase (SAT) activity
      did not change by 12 h after serum exposure. Preincubation of the cells with 10(
      8)M 1,25-(OH)2D3 for 48 h attenuated the serum-induced rise in ODC activity by 12
      h. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, inhibited
      the serum-stimulated [3H]thymidine incorporation. Simultaneous addition of 25
      microM putrescine reversed the inhibitory effect of DFMO. In summary, it was
      strongly suggested that polyamine is intimately involved in the proliferation of
      parathyroid cells and that 1,25-(OH)2D3 inhibited parathyroid cell growth through
      suppression of ODC activity.

PMID- 7565447
TI  - Time-lapse microcinematography of osteocytes.
AB  - We succeeded in the isolation of osteocytes from parietal bones of 16-day-old
      chick embryos. Isolated osteocytes showed a typical stellate morphology. More
      than 95% of these cells reacted with the osteocyte-specific antibody OB 7.3. In
      culture osteocytes formed gap junctions with each other, as could be established
      by ACAS. Sixteen-millimeter time-lapse microcinematography of the cells also
      demonstrated the formation of intercellular connections and gap junctions, and
      portrayed the interaction between osteocytes and osteoclasts: osteocytes seemed
      to inhibit osteoclast activity. This cinematography also showed the ability of
      osteocytes to proliferate after they had been disconnected from each other.
      Thereafter these cells redifferentiated into osteoblasts that became embedded in
      bone matrix produced by themselves. These findings suggest that osteocytes might
      be involved in bone formation during remodeling.

PMID- 7565448
TI  - Cellular and molecular mechanisms of bone resorption.

PMID- 7565450
TI  - Impaired response of human osteosarcoma (MG-63) cells to human parathyroid
      hormone induced by sustained exposure to high glucose.
AB  - It is known that osteopenia is frequently associated with diabetes mellitus.
      Although its mechanism is not well understood, impaired bone formation due to an
      osteoblast deficit seems to be a major factor as reflected by a fall in serum
      levels of osteocalcin and by the findings of low bone formation with bone
      histomorphometry. In the present study, we studied the effect of high glucose
      conditions on osteoblast by examining the responsiveness of human osteosarcoma
      (MG-63) cells to human parathyroid hormone 1-34 [hPTH-(1-34)]. MG-63 cells were
      cultured either with 5.5 mM glucose (normal glucose), 55.0 mM glucose (high
      glucose) or 5.5 mM glucose plus 49.5 mM mannitol (high mannitol) condition for 7
      days. Both an increase in cAMP levels and an immediate increase in [Ca2+]i,
      induced by hPTH(1-34), were significantly lower in high glucose-treated cells
      than in those treated with normal glucose or high mannitol. Basal cAMP levels in
      the cells after a 7-day culture in high glucose conditions were significantly
      higher than in those in the other two groups. We concluded that high glucose
      specifically impaired the response to hPTH(1-34). This impairment seemed to arise
      from an increase in intracellular cAMP levels, which is reported to induce
      downregulation of PTH receptors.

PMID- 7565451
TI  - Impaired vitamin D metabolism and response in spontaneously diabetic GK rats.
AB  - Several studies of diabetes mellitus patients have demonstrated abnormalities in
      calcium, phosphate and vitamin D metabolism. In an earlier study, the authors
      reported impaired renal processing of phosphate in spontaneously diabetic GK
      rats, an animal model of type II diabetes mellitus. In the present study, which
      represents an extension of the earlier study, vitamin D metabolism and response
      are examined in 20-week-old GK rats. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]
      was found to be lower in GK rats than in Wistar rats. After intraperitoneal
      administration of 0.5 micrograms/kg 1,25-(OH)2D, serum calcium increased in GK
      rats, but not in Wistar rats, while serum phosphate remained unchanged in GK
      rats, but increased in Wistar rats. Although serum 1,25-(OH)2D rose abruptly in 3
      h and decreased thereafter in both GK and Wistar rats, the decrease in serum 1,25
      (OH)2D at 6 h was more marked in GK rats than in Wistar rats. Serum 24,25
      dihydroxyvitamin D was consistently higher in GK rats than in Wistar rats.
      Northern blotting and dot blotting with use of a cDNA probe for the 24
      hydroxylase gene showed an increased expression of the gene in the kidney of GK
      rats. These results demonstrate impaired vitamin D metabolism in GK rats.
      Increased activity of 24-hydroxylase, in addition to impaired phosphate
      metabolism, may play a role in impaired vitamin D metabolism in GK rats.

PMID- 7565452
TI  - Biological activities of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 on
      human promyelocytic leukemic HL-60 cells: effects of fetal bovine serum and of
      incubation time.
AB  - The hexafluorinated vitamin D3 analog, 26,26,26,27,27,27-hexafluoro-1,25
      dihydroxyvitamin D3[F6-1,25-(OH)2D3] is more potent than 1,25-dihydroxyvitamin D3
      [1,25-(OH)2D3] regarding various physiological effects. When the biological
      potencies of vitamin D3 analogs were assessed 24 h after the addition by the
      induction of 24-hydroxylation activity in the human promyelocytic leukemia cell
      line, HL-60,F6-1,25-(OH)2D3 was 6 times as potent as 1,25-(OH)2D3 in a medium
      containing 5% fetal bovine serum. When the cells were cultured in a serum-free
      medium, F6-1,25-(OH)2D3 was only equipotent to 1,25-(OH)2D3. Considering a
      previous report demonstrating a weaker binding of F6-1,25-(OH)2D3 to serum
      vitamin D-binding protein (DBP) than 1,25-(OH)2D3, it seems that the resultant
      greater free fraction of F6-1,25-(OH)2D3 might account for its greater activity
      in a serum-containing medium. As assessed by the suppression of cell
      proliferation and the induction of cell differentiation along the
      monocyte/macrophage pathway which requires as long as 96 h for their assessment,
      the potency ratio of F6-1,25-(OH)2D3 to 1,25-(OH)2D3 increased as the levels of
      fetal bovine serum increased. It was of great interest that F6-1,25-(OH)2D3 was
      still significantly more potent than 1,25-(OH)2D3 even in a serum-free medium.
      Together with the data indicating the equipotency of F6-1,25-(OH)2D3 and 1,25
      (OH)2D3 in the induction of 24-hydroxylation activity, it was suggested that
      decreased metabolic inactivation might contribute in part to the higher potency
      of F6-1,25-(OH)2D3 in the long-term effect.

PMID- 7565453
TI  - Effects of dietary vitamin D intake on plasma levels of parathyroid hormone and
      vitamin D metabolites in healthy Japanese.
AB  - To clarify the nutritional status of vitamin D in Japanese, effects of dietary
      intake of vitamin D on plasma levels of intact and highly sensitive parathyroid
      hormone (I-PTH and HS-PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin
      D (1,25(OH)2D), calcium (Ca) and phosphorus (P(i)) in 79 healthy Japanese were
      investigated. The plasma levels of 25-OH-D in men were significantly higher than
      those in women, whereas those of HS-PTH in men were significantly lower than
      those in women. The levels of 25-OH-D in men were generally higher than those in
      women. Significant correlations were observed between the dietary vitamin D
      intake and the plasma 25-OH-D or HS-PTH levels. Correlations between the plasma
      25-OH-D levels and the plasma HS-PTH levels were also significant. These results
      suggest that dietary intake of sufficient amounts of vitamin D is effective for
      improving the vitamin D nutritional status through normalizing PTH levels.

PMID- 7565454
TI  - Influence of serum phosphate on the efficacy of oral 1,25-dihydroxyvitamin D3
      pulse therapy.
AB  - In patients with a moderate degree of renal insufficiency, restriction of dietary
      phosphate suppresses PTH secretion by increasing serum calcitriol. However, this
      may not operate in advanced renal failure. The present study was designed to
      evaluate the influence of serum phosphate levels on PTH secretion in oral 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3] pulse therapy. 22 patients with secondary
      hyperparathyroidism [carboxy-terminal PTH (c-PTH) concentration: 19.5+/-13.9
      ng/ml, mean +/-SD] received oral doses of 1,25(OH)2D3 (3.0-4.0 micrograms) twice
      a week, each at the end of hemodialysis, for 12 weeks. Doses of phosphate binders
      remained unchanged throughout this period. Patients were divided into two groups:
      group A (11 subjects) with mean serum phosphate levels of less than 6.0 mg/dl and
      group B (11 subjects) with levels of 6.0 mg/dl and above. There was no
      significant difference in the average corrected serum calcium levels. The
      reduction in serum intact PTH levels was greater in group A than in group B. A
      negative correlation (r = -0.48; p < 0.05) was observed between mean serum
      phosphate levels and the percent decrease in serum c-PTH levels. The findings of
      this study indicate an important role for dietary phosphate reduction in oral
      1,25(OH)2D3 pulse therapy and suggest that serum phosphate reduction may play a
      part in suppressing PTH secretion through a mechanism independent of 1,25(OH)2D3
      and plasma calcium levels.

PMID- 7565455
TI  - Effect of calcium supplementation on bone density and parathyroid function in
      elderly subjects.
AB  - The effect of calcium supplementation on secondary hyperparathyroidism of old age
      depends on the intestinal absorption of the calcium preparation used. In order to
      test the bioavailability and clinical usefulness of a new calcium preparation,
      heated oyster shell-seaweed calcium (HOSS Ca), a randomized, prospective, double
      blind comparison of HOSS Ca, calcium carbonate and placebo was carried out in 58
      hospitalized women with a mean age of 82. Group A received 900 mg Ca/day Ca as
      HOSS Ca, group B 900 mg Ca/day as CaCO3 and group C placebo in addition to the
      basic hospital diet containing approximately 600 mg Ca/day. After 18 months,
      lumbar spine bone mineral density (BMD) measured by DPX was 106.1 +/- 3.5% (mean
      +/- SEM) of the pretrial basal value in group A, 99.8 +/- 3.8% in group B and
      90.9 +/- 3.4% in group C (A bu not B significantly higher than C). Midradial BMD
      measured by DPX was 99.3 +/- 1.3% in A, 94.8 +/- 4.0% in B and 85.5 +/- 6.2% in
      C. The ratio of whole body calcium content between the 12th and 18th month was
      96.5 +/- 1.7% in A, 90.1 +/- 2.7% in B and 89.8 +/- 1.3% in C (A but not B
      significantly smaller than C). Final/baseline ratio of urinary Ca/creatinine was
      91.7 +/- 11.1 in A, 111.4 +/- 18.9 in B and 125.2 +/- 12.6 in C.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7565458
TI  - Activation of the Ca2+ message system by parathyroid hormone is dependent on the
      cell cycle.
AB  - Putative osteoblastic UMR 106-01 cells exhibit heterogeneous intracellular
      calcium [Ca2+]i responses to parathyroid hormone (PTH). To determine whether this
      phenomenon is secondary to cell cycle asynchrony, UMR 106-01 cultures were
      synchronized at the G1/S boundary using a sequential thymidine-aphidicolin
      treatment. Five hours after release from the block > 80% of the cells are in S
      phase, while nontreated confluent cultures are in G1. Using video image analysis
      of single cells loaded with fura-2, PTH (10-(7) M) induced transient increases in
      [Ca2+]i preferentially in cells in S phase, with 82% response frequency whereas
      cells in G1 phase responded poorly to PTH with only 10% response frequency. In
      contrast, cell response to fetal calf serum was more frequent in G1 than in S
      phase. Pretreatment with La3+, nifedipine or pertussis toxin reduced both the
      frequency and amplitude of the PTH response in S phase to values comparable to
      those observed in cells in G1 phase. There was no significant difference in
      inositol trisphosphate generated by PTH stimulation in either phase. Thus, the
      heterogeneous osteoblastic [Ca2+]i responsive to PTH is cell cycle-dependent with
      the change in the G1 to the S phase mode of response dependent on active coupling
      between the PTH receptor and a Ca2+ channel via a pertussis toxin-sensitive G
      protein.

PMID- 7565456
TI  - A small dose of human parathyroid hormone(1-34) increased bone mass in the lumbar
      vertebrae in patients with senile osteoporosis.
AB  - Intermittent treatment with human parathyroid hormone (hPTH) has been shown to
      increase cancellous bone mineral density (BMD) in osteoporosis, but its effects
      on cortical bone remain controversial. In this study, the effects of hPTH(1-34)
      administered at a dose of 6 micrograms (20 units) per day subcutaneously for 26
      weeks were investigated in 16 patients with senile osteoporosis. The changes in
      BMD in lumbar vertebrae were measured using dual energy x-ray absorptiometry. BMD
      in the second metacarpal bone was simultaneously measured with radiogrammetry to
      find changes in BMD in cortical bone. Serum and urinary biochemical parameters
      were also evaluated. The lumbar BMD increased significantly at the end of the
      treatment without decrease in the cortical bone mass. Biochemical markers of bone
      formation were also elevated, while markers of bone resorption did not show
      striking changes during the treatment. In conclusion, daily administration of low
      doses of hPTH(1-34) stimulated bone formation and increased bone mass in patients
      with senile osteoporosis without combination with another therapeutic agent.

PMID- 7565457
TI  - Calcium, why and how much?
AB  - Although calcium (Ca) is pivotal for the prevention of osteoporosis, its role in
      the prevention of other unrelated diseases such as arterial hypertension, cancer
      of the colon and nephrolithiasis is perplexing. No unitarian hypothesis
      explaining these unrelated effects of Ca has been postulated. Cytosolic Ca
      concentration is 10,000-fold lower than in the extracellular space, and this
      gradient is tightly maintained. Abnormal elevation of cytosolic Ca causes cell
      damage and death. Parathyroid hormone is a Ca agonist and the suppression of its
      secretion by Ca could explain the beneficial role of Ca intake in multiple
      diseases. Thus, parathyroid ablation improves hypertension in rats and
      cardiomyopathy in hamsters. Since anthropologic data suggests a higher Ca intake,
      of approximately 1,600 1,600 mg/day, in preneolithic than in modern diets, it is
      likely that our levels of PTH on genetically predisposed subjects with a loose
      cellular Ca control may aggravate frequent modern diseases and the process of
      aging. A higher Ca intake in both sexes should be one of the goals of preventive
      medicine of our time.

PMID- 7565460
TI  - Parathyroid hormone and hypothalamo-pituitary function.

PMID- 7565459
TI  - A Ca2+ channel in renal epithelial cells introduced by parathyroid hormone.
AB  - To investigate the mechanism of Ca2+ influx after hormonal stimuli, patch
      clamping with [Ca2+]i fluorescence measurement was performed in single renal
      proximal epithelial cells. A Ca2+ current appeared along with a rise in [Ca2+]i
      during parathyroid hormone addition to the bath, but not when the hormone was
      inside the cell-attached pipette. The Ca2+ channel, possessing linear I-V, was
      nonselective for cations, most active in hyperpolarized--membranes and showed
      oscillatory fluctuations in opening, which disappeared after excision. GTP gamma
      S opened the channel that had disappeared, which was suppressed by GDP beta S.
      These data show a PTH-responsive Ca2+ channel for which GTP/GDP may act as second
      messenger to open the latent Ca2+ channel.

PMID- 7565461
TI  - Parathyroid hormone and B cell function in dialysis patients and experimental
      chronic renal failure.

PMID- 7565462
TI  - Excessive level of parathyroid hormone may induce the reduction of recombinant
      human erythropoietin effect on renal anemia.
AB  - We examined the effect of total parathyroidectomy (PTX) on renal anemia in 20
      dialysis patients with secondary hyperparathyroidism. We obtained the following
      results. (1) Before PTX, 13 of these patients were not treated with
      erythropoietin (EPO) while the remaining 7 patients received EPO therapy. (2) In
      8 out of 13 cases without recombinant human EPO treatment before PTX, a 10%
      increase in RBC was observed after PTX. (3) In 7 of the patients who were treated
      with EPO before PTX, anemia was improved after PTX despite discontinuation of EPO
      therapy in 2, a reduced dose of EPO in 3 and the same dose of EPO in 2. Our data
      is consistent with the notion that elevated blood levels of PTH in patients with
      chronic renal failure participate in the genesis of anemia of renal failure.

PMID- 7565463
TI  - PTH, chronic renal failure and myocardium.
AB  - The heart is a target organ for parathyroid hormone (PTH), and the action of this
      hormone on the myocardium may be mediated through the ability of PTH to increase
      cytosolic calcium ([Ca2+]i) in the myocardial cells. Such a property of PTH may
      be responsible for rise in [Ca2+]i in chronic renal failure (CRF). Our study
      examined these issues. The data from this study showed: (1) PTH increases [Ca2+]i
      of cardiac myocytes, (2) this action is receptor-mediated and is produced by
      activation of the L-type calcium channels following stimulation of G protein(s),
      (3) the rise in [Ca2+]i is due to both augmented entry of calcium into the
      myocytes and mobilization of calcium from sarcoplasmic reticulum by a calcium
      induced calcium release mechanism, (4) CRF is associated with a significant rise
      in basal levels of [Ca2+]i of cardiac myocytes, (5) this effect is mediated by
      the state of secondary hyperparathyroidism of CRF, and (6) the pathways through
      which excess PTH in CRF generates this effect include both increased entry of
      calcium into cardiac myocytes and decreased exit of this ion out of these cells.

PMID- 7565464
TI  - Effect of parathyroid hormone on left ventricular diastolic function in patients
      with primary hyperparathyroidism.
AB  - To evaluate the effect of parathyroid hormone (PTH) on diastolic function, left
      ventricular (LV) diastolic filling dynamics were studied using pulsed Doppler
      echocardiography in patients with untreated primary hyperparathyroidism (HPT;
      mean age 59 years) and control subjects. In patients with primary HPT, the ratio
      of peak flow velocity of atrial filling wave to peak flow velocity of early
      filling wave (A/E) was studied immediately before and 1 month after
      parathyroidectomy (PTX). A/E is significantly higher in the patients with primary
      HPT than in the control subjects. A/E decreased significantly after PTX. A/E was
      strongly correlated with PTH levels, but not with calcium levels in patients with
      primary HPT. It is concluded that LV diastolic function is abnormal in patients
      with primary HPT, which could result from elevated PTH rather than hypercalcemia.

PMID- 7565466
TI  - New actions of parathyroid hormone. Introduction.

PMID- 7565465
TI  - Effects of parathyroidectomy on left ventricular mass in patients with
      hyperparathyroidism.
AB  - The effects of parathyroidectomy on left ventricular muscle volume and mechanical
      performance were evaluated echocardiographically in 24 patients with secondary
      hyperparathyroidism due to chronic renal failure and in 7 with primary
      hyperparathyroidism. Intraventricular septum and posterior wall thickness, left
      ventricular end-diastolic diameters, shortening fraction, ejection fraction, and
      left ventricular mass index were measured by M mode recording by the parasternal
      short axis view prior to parathyroidectomy as baseline and repeated 12 months
      after parathyroidectomy. Serum basal carboxyterminal parathyroid hormone levels
      in patients with secondary hyperparathyroidism (34.4 +/- 13.7 ng/ml) were
      significantly higher than in those with primary hyperparathyroidism (3.4 +/- 5.1
      ng/ml; p < 0.0001). At 12 months after parathyroidectomy, intraventricular septum
      and posterior wall thickness, left ventricular end-diastolic diameter and left
      ventricular mass index were reduced from 11.8 +/- 3.1 mm, 10.9 +/- 1.7 mm, 53.8
      +/- 6.3 mm, 200.8 +/- 57.1 g/m2 to 10.0 +/- 2.1 mm (p < 0.05), 9.8 +/- 1.9 mm (p
      < 0.05), 50.7 +/- 7.2 mm (p < 0.05), 149.6 +/- 38.7 g/m2 (p < 0.0001), in
      patients with secondary hyperparathyroidism. In patients with primary
      hyperparathyroidism, all echocardiographic parameters remained in the normal
      range and did not show any significant changes before or after parathyroidectomy.
      From this study, parathyroid hormone at extremely high concentrations as seen in
      secondary hyperparathyroidism appears to be a cardiotoxic substance. Therefore,
      all patients with secondary hyperthyroidism should be examined by
      echocardiography and parathyroidectomy should be considered if myocardial
      hypertrophy is present.

PMID- 7565467
TI  - Relation between parathyroid hormone and cardiac function in long-term
      hemodialysis patients.
AB  - Radionuclide ventriculographic and echocardiographic assessments of left
      ventricular cardiac function were studied in 46 long-term maintenance
      hemodialysis patients, and comparison of cardiac function pre- and post
      parathyroidectomy in 10 hemodialysis patients with secondary hyperparathyroidism
      was investigated. In long-term hemodialysis patients, impairment of cardiac
      function was observed in 80.4%. In an overall study of 46 patients, no
      correlation between intact parathyroid hormone (iPTH) level and left ventricular
      ejection fraction (LVEF) was observed, but a significant (p < 0.05) negative
      correlation was observed in patients with an iPTh blood level over 200 pg/ml. A
      negative correlation between fractional fiber shortening and an iPTh level over
      200 pg/ml was observed (p < 0.05). There was neither a correlation between the
      iPTH level and left ventricular (LV) mass, nor was there a correlation between
      the iPTH level and wall thickness. After parathyroidectomy, systolic and
      diastolic blood pressure, cardiothoracic ratio, LVEF, and LV mass decreased
      significantly (p < 0.05), but no significant difference was detected in cardiac
      thickness. In summary, the present data suggest that high levels over 200 pg/ml
      of the iPTH in long-term hemodialysis patients adversely affect the myocardial
      function, induce cardiac hypertrophy and cause high arterial blood pressure.
      After parathyroidectomy, the cardiac function improved with a reduction of
      cardiac mass and an improvement of cardiac contraction.

PMID- 7565468
TI  - Hypertension and primary hyperparathyroidism: the role of adrenergic and renin
      angiotensin-aldosterone systems.
AB  - Primary hyperparathyroidism (HPTH) is frequently associated with hypertension. To
      date, the relationship between these two conditions is still not clear. We have
      studied 34 consecutive patients with primary HPTH due to a parathyroid adenoma.
      The diagnosis was later surgically confirmed in 32 cases. Ten of thirty-four HPTH
      patients were hypertensive. Before adenomectomy (PTHX) and 1-2 months after PTHX,
      we measured the following parameters in all patients: circulating levels of total
      and ionized Ca, intact immunoreactive parathormone (iPTH) (1-84), plasma renin
      activity (PRA), aldosterone, and daily total urinary catecholamine excretion.
      Moreover, 10 hypertensive HPTH patients, 10 normotensive HPTH patients, compared
      to 10 to 10 sex- and age-matched healthy normotensive subjects, underwent an
      acute norepinephrine test to assess vascular reactivity to a pressor agent.
      Before PTHX, no significant difference was observed between normotensive and
      hypertensive patients in all the above-mentioned variables, except for PRA and
      plasma aldosterone levels which were higher in hypertensive patients.
      Furthermore, the pressor response to the norepinephrine test was significantly
      greater in hypertensive HPTH patients than in the other 2 groups. After PTXH,
      serum Ca and intact iPHT (1-84) levels were reduced to normal values in all
      patients, while blood pressure, PRA and plasma aldosterone levels became normal
      in 8 of 10 hypertensive patients. The pressor response to the norepinephrine test
      was similar in the 2 groups. These results are consistent with the hypothesis of
      a direct effect of PTH on renin secretion which could contribute to the
      pathogenesis of hypertension and to the vessels sensitization to pressor agents.

PMID- 7565469
TI  - Implication of parathyroid hormone for the development of hypertension in young
      spontaneously hypertensive rats.
AB  - The purpose of this study is to elucidate the role of parathyroid hormone (PTH)
      in the development of hypertension in young spontaneously hypertensive rats
      (SHR). Parathyroidectomy (PTX) or sham surgery was performed on 6-week-old male
      SHR, and 3 weeks later human PTH (hPTH) or saline was infused subcutaneously over
      2 weeks using a minipump. PTX significantly attenuated the development of
      hypertension and reduced serum vitamin-D concentrations. PTX also augmented the
      depressor response to acetylcholine before N-nitro-L-arginine (L-NNA), although
      it remained unchanged after L-NNA. The cardiovascular reactivity to exogenous
      noradrenaline and angiotensin II was not affected by PTX. The chronic
      administration of hPTH reversed these effects. We conclude that PTH plays an
      important role in the development of hypertension, through modulating the release
      of endothelium-derived relaxing factor, in young SHR.

PMID- 7565470
TI  - Some aspects of the anabolic action of parathyroid hormone.

PMID- 7565471
TI  - Non-traditional actions of parathyroid hormone: an overview.

PMID- 7565473
TI  - Pathogenesis and management of parathyroid hyperplasia in chronic renal failure:
      role of calcitriol.

PMID- 7565472
TI  - Pathogenesis of secondary hyperparathyroidism.

PMID- 7565474
TI  - The role of cytokines in inflammatory glomerular injury.
AB  - T lymphocyte and macrophage-derived cytokines play an important role in the
      pathogenesis of inflammatory glomerular injury by exerting both effector and
      regulatory actions. In this article, evidence implicating these cytokines in the
      pathogenesis of experimental and human glomerulonephritis will be reviewed. The
      possibility that cytokines derived from different T lymphocyte subpopulations
      modulate glomerular inflammation by exerting opposite actions on macrophages will
      be discussed.

PMID- 7565475
TI  - Role of leukotrienes and lipoxygenases in glomerular injury.
AB  - The 5-lipoxygenated metabolites of arachidonic acid, the leukotrienes, are
      increasingly recognized as major mediators of early glomerular hemodynamic and
      structural deterioration during experimental glomerulonephritis. Generation of
      these metabolites is largely by infiltrating leukocytes, but can also occur by
      intrinsic glomerular cells via transcellular metabolism of intermediates. In
      several animal models of glomerulonephritis and other renal pathologic states,
      leukotrienes have been shown to exert adverse effects in the glomerulus.
      Leukotriene B4 augments neutrophil infiltration, and leukotrienes C4 and D4
      mediate potent vasoconstrictor effects on the glomerular microcirculation.
      Selective blockade of the 5-lipoxygenase pathway in the course of glomerular
      injury is associated with a significant amelioration of the deterioration of
      renal hemodynamic and structural parameters. 15-S-hydroxyeicosatetraenoic acid
      (15-S-HETE), the immediate product of arachidonate 15-lipoxygenase, and the
      lipoxins, which are produced by sequential 15- and 5- or 5- and 12-lipoxygenation
      of arachidonic acid are also generated in the course of glomerular injury. These
      eicosanoids have actions that contrast with those of leukotrienes. 15-S-HETE
      antagonizes leukotriene-induced neutrophil chemotaxis and lipoxin A4 antagonizes
      the effects of leukotrienes C4 and D4 on the glomerular microcirculation. The
      contrasting effects of 5- and 15-lipoxygenase products may represent endogenous
      pro- and anti-inflammatory influences that could ultimately regulate the extent
      and severity of glomerular inflammation. The recent availability of safe and
      effective 5-lipoxygenase inhibitors will be helpful to test the effect of
      blocking leukotriene production on the course of human glomerulonephritis and
      other disease states.

PMID- 7565476
TI  - Multiple roles for platelet-derived growth factor in renal disease.
AB  - Platelet-derived growth factor (PDGF) is a pleiotropic cytokine, that is
      synthesized by various resident renal cells and also by infiltrating cells. The
      best established role for PDGF in the kidney is the mediation of glomerular
      mesangial cell proliferation. There is also evidence to suggest an involvement of
      PDGF in the regulation of renal extracellular matrix turnover, the
      chemoattraction of mesangial cells and/or other cells to sites of injury, the
      regulation of glomerular hemodynamics, and lipoprotein uptake in the glomerulus.
      The first studies investigating the efficacy of anti-PDGF therapy in glomerular
      disorders point to a potentially novel approach to treat progressive renal
      disease.

PMID- 7565477
TI  - Endothelin in the progressive renal disease of glomerulopathies.
AB  - Endothelin (ET) isopeptides are synthetized in the kidney and act as local
      hormones with an impressive number of diverse autocrine and paracrine functions.
      A variety of proinflammatory and vasoactive agents including thrombin,
      transforming growth factor beta, angiotensin II as well as mechanical forces
      enhance the renal synthesis of ET. Two receptor subtypes, ETA and ETB, are widely
      expressed in the kidney, coupled to multiple intracellular signal transduction
      pathways that mediate distinct activities. Renal vessels are peculiarly sensitive
      to the vasoconstrictive effect of ET, which, infused in the kidney, decreases
      renal blood flow and glomerular filtration rate. This effect, together with the
      capability of ET to induce contraction and proliferation of mesangial cells, as
      well as accumulation of mesangial matrix proteins, have suggested that ET may
      participate in the renal events that lead to renal disease progression. Evidence
      is now available that renal ET does play a role in the process of progressive
      renal injury in chronic models of renal disease to the extent that the selective
      pharmacological manipulation of ET pathway has a major positive impact on the
      progression of the disease. By contrast, more work is necessary to define the
      role of ET in the pathophysiology of human glomerulopathy. The recent
      availability of orally active compounds with potential human use, may hopefully
      speed progress in the area.

PMID- 7565478
TI  - Mediators of hyperglycemia and the pathogenesis of matrix accumulation in
      diabetic renal disease.
AB  - Renal injury in diabetes mellitus is a major cause of morbidity and mortality in
      diabetic patients. There is a clear correlation between the degree of glomerular
      as well as tubulointerstitial lesions and the development of reduced glomerular
      filtration rate. The important role of hyperglycemia in the genesis of diabetic
      renal disease has been strengthened by the application of tissue culture
      techniques. Recent in vitro studies, first in tubular epithelial cells and
      subsequently in the three glomerular cell types, have provided supportive
      evidence that high ambient glucose per se stimulates the synthesis of
      extracellular matrix components. Increased matrix synthesis and decreased
      degradation are thought to contribute to matrix accumulation in diabetic
      nephropathy. These processes are not mutually exclusive and they may be operating
      simultaneously but at different rates, with increased synthesis predominating
      early and decreased breakdown later in the course of the disease. Likely
      mediators of the effects of high glucose involve activation of the polyol
      pathway, altered myo-inositol metabolism, increased protein kinase C activity,
      and/or nonenzymatic glycation of various matrix proteins. A role for various
      growth factors, especially transforming growth factor-beta, also seems likely.
      However, the details of the cell-signaling mechanisms and the putative molecular
      mediators of the effect of hyperglycemia remain to be firmly established.

PMID- 7565479
TI  - Cellular mechanisms of tubule hypertrophy and hyperplasia in renal injury.
AB  - Tubular cells can either unergo hyperplasia or hypertrophy, two totally different
      growth responses. Hyperplasia with mitogenesis of tubular cells plays a central
      role in the regeneration of functional tubular epithelium subsequent to acute
      tubular necrosis. Several growth factors acting in concert are involved in this
      proliferative response of tubular cells. The molecular mechanisms how mitogenic
      signals are transduced to the nucleus are relatively well characterized. Complex
      oscillation patterns of cell cycle-associated proteins like cyclins and various
      kinases are pivotal for the progression of quiescent tubular cells through
      mitosis. In contrast to the mitogenic growth response of regenerating tubular
      cells, cellular hypertrophy is less well understood. Hypertrophic cells are
      arrested in the G1-phase of the cell cycle and increase their size, protein and
      RNA content, but do normally not replicate their DNA. Such an enlargement of
      tubular cells often occurs in more chronic situations of renal damage in which
      remnant nephrons adapt their function to the increasing need. However, evidence
      exists that hypertrophic tubules are finally joined into the process of
      maladaptation of renal function leading to tubular atrophy, interstitial
      scarring, and progression of renal disease. It appears that transforming growth
      factor-beta is involved in the hypertrophy of tubular cells. The present review
      will address more recent progress in understanding the mechanism of tubular
      growth at a cellular level. A better knowledge of the molecular factors may
      ultimately lead to therapeutic strategies preventing the progression of renal and
      speeding up renal recovery after acute renal failure.

PMID- 7565481
TI  - Angiotensin II-mediated renal injury.
AB  - During the past decade, experimental and clinical evidence has indicated an
      important role for the renin-angiotensin system in the progressive destruction of
      nephrons in a wide variety of chronic renal diseases. Studies have indicated that
      in the subtotally nephrectomized rat model of progressive glomerulosclerosis, in
      experimental diabetes mellitus, in the chronic phase of puromycin aminonucleoside
      induced nephrotic syndrome and in Heymann's nephritis, angiotensin-converting
      enzyme (ACE) inhibitors dramatically preserve both nephron structure and
      function. Clinical studies have similarly noted that chronic administration of
      ACE inhibitors inhibits progression of renal failure in type I diabetes and type
      II diabetes as well as primary glomerulopathies, sickle cell nephropathy,
      systemic lupus erythematosis, chronic pyelonephritis and adult polycystic kidney
      disease. Current evidence suggests that the beneficial effect of ACE inhibitors
      is primarily due to inhibition of angiotensin II production, and there is strong
      suggestive evidence for increases in local intrarenal activation of the renin
      angiotensin system in these conditions. In obstructive uropathy, activation of
      the renin-angiotensin system has also been shown to be an important aspect of the
      early functional changes and may be of importance in the subsequent generation of
      interstitial fibrosis. In the obstructed kidney, renin and angiotensinogen
      production increase and type I angiotensin receptors decrease. Inhibitors of
      angiotensin II production and angiotensin II action partially reverse the
      vasoconstriction and the reduced renal blood flow, and abolish the changes in
      expression of AT1 MRNA induced by obstruction. Studies suggest that the
      angiotensin-mediated increases in tubulointerstitial fibrosis may be mediated by
      increased production of transforming growth factor-beta.

PMID- 7565480
TI  - The pathogenesis of tubulointerstitial disease associated with
      glomerulonephritis: the glomerular cytokine theory.
AB  - Numerous studies have suggested that tubulointerstitial disease has a major
      impact on the overall function and prognosis of glomerular disease. The mechanism
      by which tubulointerstitial disease develops in patients with glomerular and
      other diseases is unknown. In this review, we discuss the hypothesis that factors
      released from injured glomeruli act on tubules and interstitial cells to induce
      expression of chemotactic and adhesive factors that attract mononuclear cells
      into the interstitium. Evidence is provided that osteopontin is one candidate
      leukocyte adhesive factor involved in this process, but others are likely
      involved. The recruited leukocytes (primarily macrophages) then release
      inflammatory mediators that injure tubular cells and activate interstitial
      fibroblasts, resulting in tubulointerstitial injury with eventual fibrosis.

PMID- 7565482
TI  - Tumor necrosis factor in renal injury.
AB  - Inflammatory diseases of the renal glomerulus and tubulointerstitium are
      characterized by destructive and restorative processes. These alterations are
      mediated by soluble molecules, including cytokines that instruct target cells to
      alter their proliferation, differentiation phenotype, secretion and migration.
      One of these cytokines is tumor necrosis factor-alpha (TNF alpha). Its expression
      within the glomerulus has been observed in both resident cells and infiltrating
      monocytes/macrophages in response to cell stimulation with chemicals, immune
      complexes, bacterial lipopolysaccharides, and advanced glycosylation end
      products. Its release can be amplified by deposits of terminal complement
      proteins (C5b-9) or formation of platelet-activating factor and reactive oxygen
      species, and, on the contrary, blunted by that of prostaglandins or anti
      inflammatory interleukin (IL)-6 and IL-10. The roles of TNF alpha in the
      pathogenesis of glomerular diseases include reduction of blood flow and
      filtration rate, alteration of the barrier function of capillary wall, formation
      of capillary thrombi and infiltration of the structure by blood-borne cells.
      Expression of TNF alpha has been observed in tubulointerstitium as well, mainly
      in proximal tubular epithelial cells. In vitro, this expression can be amplified
      by IL-1 and, inversely, suppressed by immunosuppressive drugs. Roles of TNF alpha
      in tubulointerstitium remain largely undefined, but may include infiltration of
      the interstitium by inflammatory cells and alteration in tubular transport of
      fluid and electrolytes. Extensive study will be necessary to further elucidate
      intracellular signals induced by TNF alpha binding to target cells within the
      kidney and thus to establish possibilities of therapeutic intervention.

PMID- 7565483
TI  - Role of intrarenal endothelin in the generation and maintenance of hypertension.
AB  - Alterations in the renal metabolism and/or actions of endothelin-1 (ET-1) may be
      involved in the pathogenesis and maintenance of essential and renal parenchymal
      hypertension. ET-1 has the potential to modify a broad range of renal functions
      involved in controlling systemic blood pressure. First, the kidney clears a large
      percentage of ET-1 from the blood; decreased renal ET-1 clearance may contribute
      to hypertension occurring in the setting of chronic renal failure. Second, ET-1
      potently constricts the renal vasculature resulting in increased fluid retention
      and possibly contributing to glomerular sclerosis; enhanced renal vascular and
      glomerular ET-1 production and target cell actions may play a role in essential
      hypertension or hypertension accompanying chronic renal failure, cyclosporine
      administration, or erythropoietin therapy. Lastly, ET-1 is also an autocrine
      inhibitor of collecting duct sodium and water reabsorption; reduced nephron ET-1
      production may result in fluid retention in essential hypertension. Determination
      of the true role that ET-1 plays in the pathogenesis of the varied forms of
      hypertension awaits the development of safe, potent, and specific endothelin
      antagonists.

PMID- 7565484
TI  - Renal tubule cell repair following acute renal injury.
AB  - Experimental data suggests the recovery of renal function after ischemic or
      nephrotoxic acute renal failure is due to a replicative repair process dependent
      upon predominantly paracrine release of growth factors. These growth factors
      promote renal proximal tubule cell proliferation and a differentiation phase
      dependent on the interaction between tubule cells and basement membrane. These
      insights identify the molecular basis of renal repair and ischemic and
      nephrotoxic acute renal failure, and may lead to potential therapeutic modalities
      that accelerate renal repair and lessen the morbidity and mortality associated
      with these renal disease processes. In this regard, there is a prominent
      vasoconstrictor response of the renal vasculature during the postischemic period
      of developing acute renal failure. The intravenous administration of
      pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period
      have proven efficacious by altering renal vascular resistance, so that renal
      blood flow and glomerular filtration rate improve. ANF also appears to protect
      renal tubular epithelial integrity and holds significant promise as a therapeutic
      agent in acute renal failure. Of equal or greater promise are the therapeutic
      interventions targeting the proliferative reparative zone during the postischemic
      period. The exogenous administration of epidermal growth factor or insulin-like
      growth factor-1 in the postischemic period have effectively decreased the degree
      of renal insufficiency as measured by the peak serum creatinine and has hastened
      renal recovery as measured by the duration of time required to return the
      baseline serum creatinine values. A similarly efficacious role for hepatocyte
      growth factor has also been recently demonstrated.

PMID- 7565485
TI  - Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual
      behavior in male rats.
AB  - Prenatal maternal stress in rats and mice can demasculinize and feminize the
      sexual behavior of adult male offspring. Causal mechanisms are unknown, but one
      attractive hypothesis is that stress activation of maternal adrenal
      glucocorticoid secretion is the responsible agent. To test this hypothesis,
      pregnant rats were exposed to a variety of substances which enhance
      glucocorticoid actions. These included ACTH (20 IU of a gel preparation, SC once
      daily), corticosterone (CORT; 7 mg/kg SC in oil, three times daily), or
      dexamethasone (DEX; 0.1 mg/kg, SC once daily). Controls included noninjected dams
      and a positive stress control group (restraint under bright lights three times
      daily). All treatments reduced maternal weight gain, DEX most potently. No
      treatment altered litter size, stillbirths, or sex ratio, but DEX reduced weight
      at birth, an effect still seen at postnatal day 85. DEX, CORT, and stress reduced
      male adrenal weight at birth, while DEX and CORT altered sexual differentiation
      as measured by anogenital distance. Stress impaired adult male sexual performance
      but not the lordosis quotient following exposure of animals to stud males. DEX
      affected both measures. No other treatment had any significant effect on sexual
      behavior. No treatment altered plasma LH levels, either basal or in response to
      an estrogen challenge in adult gonadectomized males. In adulthood there was no
      treatment effect on stress reactivity, measured behaviorally or by plasma
      glucocorticoids. Correlational analysis revealed that weight gain during
      pregnancy was the single best predictor of subsequent sexual performance. It is
      concluded that prenatal dexamethasone exposure demasculinizes and feminizes male
      offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565486
TI  - Development of infants born to cocaine-abusing women: biologic/maternal
      influences.
AB  - This study investigated the influence of gestational age, birthweight,
      caregiving, and maternal personality characteristics on the development of 51 six
      month-old infants born to and being reared by cocaine-abusing mothers. Two self
      report measures were administered to the pregnant women at intake: the ASI
      (quantifying drug use) and the MCMI (describing DSM-III Axis II personality
      characteristics and Axis I clinical syndromes). Infants' biologic vulnerability
      was assessed by gestational age and birthweight. Caregiving was assessed 6 months
      later in the home, using the HOME Inventory and maternal caregiving behavior
      rating scales. Infant development was assessed in the laboratory at 6 months
      using the Bayley Scales of Infant Development. Higher Bayley scores were
      associated with heavier birthweight and increased maternal sensitivity.
      Furthermore, mothers of infants with shorter gestations were found to be more
      sensitive caregivers, whereas mothers who reported more histrionic-gregarious,
      narcissistic, borderline-cycloid, and/or paranoid personality characteristics
      during pregnancy were less sensitive caregivers. Surprisingly, mothers who
      reported more depressive symptoms during pregnancy provided more sensitive care.

PMID- 7565487
TI  - Consistent striatal damage in rats induced by 3-nitropropionic acid and cultures
      of arthrinium fungus.
AB  - Arthrinium fungi were cultivated from the samples of mildewed sugarcane which
      caused acute encephalopathy and delayed dystonia in children. The Arthrinium
      cultures (AC) contained 5 mg/ml 3-nitropropionic acid (3-NPA) after being
      inactivated and concentrated. A neuropathological study was carried out in rats
      intoxicated with 3-NPA and AC, respectively. Consistent bilateral striatal
      necrosis was found in rats with both poisonings, and the severity was well
      correlated with persistent recumbency which was a clinical indicator of the
      development of morphological brain lesions. A reproducible animal model of
      striatal damage has been produced in rats by IP injections of 10 mg/kg 3-NPA, 6
      times a day, with an interval of 1.5 h for 3-5 days. The clinical and
      neuropathological manifestations in rats dosed with AC were nearly the same as
      those dosed with 3-NPA. The striatal lesions induced by 3-NPA and AC in poisoned
      rats were in accordance with the bilateral lenticular hypodensity found by CT
      scanning in patients of mildewed sugarcane poisoning with delayed dystonia. This
      neuropathological evidence supports previous epidemiological and mycological
      findings which indicate that 3-NPA is the possible pathogen of acute mildewed
      sugarcane poisoning.

PMID- 7565488
TI  - Prenatal administration of buprenorphine using the osmotic minipump: a
      preliminary study of maternal and offspring toxicity and growth in the rat.
AB  - Buprenorphine, an opioid with mixed agonist-antagonist properties, is gaining new
      attention as an effective pharmacotherapy for opioid and possibly cocaine abuse.
      With a view to its consideration for use with pregnant clients and because so
      little is know of its potential developmental toxicity, we have carried out this
      preliminary study. Three doses of buprenorphine (BUP) were administered by
      osmotic minipump from day 8 of gestation through parturition. In addition to 0.3,
      1.0, and 3.0 mg/kg/day of BUP, a vehicle control group received sterile water via
      minipump and a nontreated control group was left undisturbed during pregnancy.
      All treated and control litters were fostered at birth to untreated dams. BUP
      produced a dose response reduction in maternal water intake but had no effect on
      maternal weight gain, the frequency of resorptions, or birthweight. BUP had no
      effect on perinatal mortality and produced inconsistent effects on postnatal
      growth. The unique chemical and pharmacological properties of this compound,
      especially its bell-shaped or asymptotic dose response effects, are discussed
      with respect to the development of an adequate animal model to evaluate
      neurobehavioral effects and assess its safety for use during pregnancy.

PMID- 7565489
TI  - In vitro neuroteratogenicity of valproic acid and 4-en-VPA.
AB  - Mouse embryos displaying 8 to 9 pairs of somites were cultured during 26 h in
      presence of 0.75 mM of VPA, or of 1 mM of 4-en-VPA. These concentrations induced
      approximately 50% of dysmorphogenic embryos. Irregular suture of caudal neural
      tube, abnormal head shape, cranial neural tube defects, and deformed optic
      vesicles were the most common defects observed with both compounds. The main
      differences in the types of dysmorphogeneses detected between the two compounds
      concerned the suture of the caudal neural tube and the telencephalic region.
      Other macroscopic effects induced by the two compounds were similar. Several of
      the observed abnormalities can be correlated with defects reported after in vivo
      exposure. The major alteration of the histological structure of the neural tube
      concerned a specific area in the hindbrain : VPA and 4-en-VPA induced an abnormal
      and irregular budding of the neuroepithelium at this level. Immunohistology with
      an antibody specific for radial glial fibers (RC-2) as well as SEM analysis
      showed a moderate effect on glial development, mainly after exposure to VPA.

PMID- 7565490
TI  - An update on incidence of FAS: FAS is not an equal opportunity birth defect.
AB  - The incidence of Fetal Alcohol Syndrome is now estimated at 0.97 cases per 1,000
      live births in the general obstetric population and 4.3% among "heavy" drinkers.
      The general incidence is more than 20 times higher in the United States (1.95 per
      1,000) compared to Europe and other countries (0.08 per 1,000). Within the United
      States, the incidence at sites characterized by low socioeconomic status, and
      African American or Native American background are about 10 times higher (2.29
      cases per 1,000) compared to sites with a predominant middle/upper SES and
      Caucasian background (0.26 per 1,000). Based on racial background, the number of
      pregnant women in the U.S. giving birth to FAS children is 2,043 per year; if
      based on socioeconomic status, the number is slightly higher 2,366. Although race
      and SES are confounded in the U.S. studies, an examination of U.S. and European
      studies suggests that the major factor associated with FAS is low SES rather than
      racial background.

PMID- 7565491
TI  - Maternal risk factors in fetal alcohol syndrome: provocative and permissive
      influences.
AB  - We present an hypothesis integrating epidemiological, clinical case, and basic
      biomedical research to explain why only relatively few women who drink alcohol
      during pregnancy give birth to children with alcohol-related birth defects
      (ARBDs), in particular, Fetal Alcohol Syndrome (FAS). We argue that specific
      sociobehavioral risk factors, e.g., low socioeconomic status, are permissive for
      FAS in that they provide the context for increased vulnerability. We illustrate
      how these permissive factors are related to biological factors, e.g., decreased
      antioxidant status, which in conjunction with alcohol, provoke FAS/ARBDs in
      vulnerable fetuses. We propose an integrative heuristic model hypothesizing that
      these permissive and provocative factors increase the likelihood of FAS/ARBDs
      because they potentiate two related mechanisms of alcohol-induced teratogenesis,
      specifically, maternal/fetal hypoxia and free radical formation.

PMID- 7565492
TI  - Medium and long-term behavioral effects in mice of extended gestational exposure
      to ozone.
AB  - CD-1 mice were continuously exposed to ozone (O3) from 6 days before the
      formation of breeding pairs to Day 17 of pregnancy. The concentrations used were
      0, 0.2, 0.4, and 0.6 ppm; the lowest-observed-effect levels for eye irritation
      and respiratory function are in the range of 0.08-0.2 ppm for both humans and
      animals (47). Ozone failed to produce significant effects on either reproductive
      performance, postnatal somatic and neurobehavioral development (as assessed by a
      Fox test battery) or adult motor activity (including within-session habituation).
      In social interaction tests performed in the pre-juvenile period (23-25 days) and
      the juvenile period (43-45 days), social response endpoints were not modified in
      O3 mice, but exploration and self-grooming showed concentration dependent effects
      (decrease and increase, respectively). Performance at 84-98 days in an eight-arm
      radial maze with water reinforcement was initially impaired in O3 mice, but the
      results were not entirely consistent; e.g., the data failed to show a
      concentration dependence of the effects. Overall, the data confirm previous
      results of an experiment with more limited exposure [pregnancy Days 7-17 (6)] by
      showing that prenatal O3 exposure, even when extended to include a period before
      the start of pregnancy and the preimplantation phase, does not produce major or
      widespread somatic and neurobehavioral effects. Some of the results, however,
      point to subtle or borderline behavioral deficits which deserve to be considered
      both in further animal experiments and in the assessment of risk to developing
      humans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565493
TI  - Effects of prenatal cocaine exposure on postnatal growth patterns of male Wistar
      rats.
AB  - The purpose of this study was to investigate basic parameters regarding the
      postnatal effects of prenatal exposure to cocaine. Timed-pregnant Wistar rats
      were injected SC with 60 mg/kg body weight/day of cocaine from gestational day 8
      to 22. Control females were nonmanipulated and given food and lib; saline females
      received saline injections and pair-fed received saline and were nutritionally
      controlled to the cocaine-treated rats. Litters were restricted to 8 pups,
      weighed every other day until postnatal day (PND) 30 and every week from PND 30
      to PND 90. The rats were perfused at PND 14, 30, and 90. The adequacy of
      adjustment of the logistic and Gompertz models to the body weights of the
      offspring was tested for the whole experimental period. The results from the
      Gompertz curve showed a higher growth rate and less time to reach 37% of expected
      mature body mass for the offspring of cocaine and pair-fed dams as compared with
      that of control and saline dams. No significant differences in the estimated
      adult weight were found among the experimental groups. The allometric
      relationship between forebrain and body weight is described by two postnatal
      growth phases with a first phase of rapid growth between PND 14 and 30 and a
      decelerating phase between PND 30 and 90. This relationship was not different
      among the experimental groups; however, the cocaine and pair-fed offspring showed
      a constant deficit in the forebrain weight as compared with the control and
      saline offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565495
TI  - Vehicle and route dependent effects of a pyrethroid insecticide, deltamethrin, on
      motor function in the rat.
AB  - Deltamethrin is a potent neuroactive pyrethroid insecticide. Literature reports
      of the in vivo potency of deltamethrin, however, vary by greater than three
      orders of magnitude in studies employing numerous vehicles and routes of
      exposure. Therefore, the present study systematically compared IP and PO routes
      of exposure to deltamethrin (0.3-1000 mg/kg) delivered to adult rats in one of
      four different vehicles (corn oil, glycerol formal, Emulphor, or
      methylcellulose). A reduction in motor activity as measured in figure-8 mazes was
      used to index the potency of this pesticide on CNS function. Dose-effect and time
      course determinations were made for each combination of vehicle and route.
      Results demonstrated that the potency of deltamethrin was dependent on both the
      route of administration and the vehicle. The ED50 for deltamethrin was 5.1 mg/kg
      when administered PO in corn oil, whereas, the ED50 was > 1000 mg/kg when
      administered PO in methylcellulose. Thus, reported discrepancies in the potency
      of deltamethrin on CNS function are at least partially attributable to route of
      administration and vehicle.

PMID- 7565494
TI  - Prenatal alcohol, marijuana, and tobacco use: infant mental and motor
      development.
AB  - These data are from a longitudinal study of prenatal alcohol and marijuana use in
      a low income sample. Half of the women were black and half were white. Women who
      used alcohol and/or marijuana during their pregnancies were light to moderate
      users; most decreased or discontinued their use after the first trimester. At the
      first follow-up phase, which occurred at a median age of 9 months, the children
      were functioning above average on the Bayley Scales of Infant Development (BSID).
      Prenatal alcohol and tobacco use did not predict BSID mental or motor scores at
      this phase. Third trimester marijuana use was associated with decreased BSID
      mental scores. Age at assessment was the most important predictor at this phase.
      The second follow-up occurred at a median age of 19 months when the group means
      for the BSID were lower. Prenatal alcohol and marijuana use did not predict
      outcome at this phase. Prenatal and current cigarette use were associated with
      decreased BSID mental scores. Demographic and environmental variables were
      important predictors at this phase.

PMID- 7565496
TI  - Alterations of mouse embryonic branchial nerves and ganglia induced by ethanol.
AB  - An immunostaining technique using monoclonal antibodies to a neurofilament
      protein has allowed us to visualize defects in the development of cranial nerves
      and ganglia of 10 to 10.5 days mouse embryos following exposure to ethanol in
      whole embryo culture. Reference patterns for development of cranial nerves and
      ganglia of control mouse embryos explanted and examined when they had 25 to 34
      pairs of somites were established. Additionally, control mouse embryos were grown
      in whole embryo culture for 48 h, with culture being initiated in embryos having
      6 to 7 somite pairs. At the end of the culture period, only minor differences
      were observed between the control groups. An experimental group of embryos was
      cultured in the presence of increasing doses (1.6, 3.2, 4, and 4.8 g/l) of
      ethanol. Defects were observed in the development of the glossopharyngeal and
      vagus nerves. These abnormalities included absence of the dorsal root (superior
      ganglion) of IX, star-like shape of inferior ganglion IX, disorganization of the
      rootlets of nerve X and abnormal fibers between the two nerves and ganglia. These
      results suggest that the migration and patterning of neural crest cells derived
      from r6 and r7 may be particularly affected by ethanol. The results also
      demonstrate the usefulness of this approach in evaluating the susceptibility of
      the developing cranial nerves to toxicant exposure.

PMID- 7565498
TI  - Reproductive and developmental toxicity of aluminum: a review.
AB  - It is well known that aluminum is a developmental toxicant when administered
      parenterally. However, until recently, there was little concern about
      embryo/fetal consequences of aluminum ingestion because bioavailability was
      considered low. The importance of the route of exposure and the chemical form of
      the aluminum compound on the developmental toxicity of this element are now well
      established. Although no evidence of maternal and embryo/fetal toxicity was
      observed when high doses of aluminum hydroxide were given orally to pregnant rats
      and mice during organogenesis, signs of maternal and developmental toxicity were
      found in mice when aluminum hydroxide was given concurrently with citric or
      lactic acids. On the other hand, studies in rabbits have shown that aluminum
      induced behavioral toxicity is greater in adult and aged animals than in young
      adults. However, maternal dietary exposure to excess A1 during gestation and
      lactation which did not produce maternal toxicity would be capable of causing
      permanent neurobehavioral deficits in weanling mice and rats. Adverse effects of
      parenteral aluminum administration on the mouse male reproductive system have
      also been reported. The embryo/fetal toxicity of aluminum administration, the
      potential reproductive toxicology of aluminum exposure, and the
      neurodevelopmental effects of aluminum are here reviewed.

PMID- 7565497
TI  - Effects of prenatal cocaine exposure on haloperidol-induced increases in
      prolactin release and dopamine turnover in weanling, periadolescent, and adult
      offspring.
AB  - Offspring of dams given 40 mg/kg cocaine SC on gestational days (GD) 8-20 (E8-20)
      (C40), dams given 0.9% saline SC on E8-20 that were pair fed and watered to C40
      dams (PF), and untreated control dams given ad lib access to food and water (LC)
      were challenged with haloperidol (0.0, 0.05, 0.10, or 0.50 mg/kg) at either 21,
      35, or 60 days postnatally (P21, 35, 60). One hour postinjection, animals were
      sacrificed, trunk blood collected for assay of prolactin, and the striatum (ST)
      and nucleus accumbens (NAc) removed. The ratio of the dopamine metabolites 3,4
      dihydroxyphenylacetic acid and homovanillic acid to dopamine (DA) as well as the
      ratio of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) to
      serotonin (5-HT) were determined in these brain regions as an index of DA and 5
      HT turnover, respectively. Assessment of 5-HIAA/5-HT ratios did not indicate any
      reliable dose or prenatal treatment effects. Reminiscent of previous findings
      obtained in C40 offspring at P11 (35), P21 C40 offspring exhibited a slightly
      reduced sensitivity to haloperidol relative to LC controls both in terms of DA
      ratios in the NAc as well as plasma prolactin levels. These findings were also
      evident in PF controls suggesting that they may be the result of prenatal
      undernutrition. Furthermore, this reduced sensitivity was not evident at the
      older test ages. At P60, planned comparisons revealed haloperidol-induced
      increases in prolactin levels in C40 males but not PF or LC males; these findings
      could potentially reflect feminization in males following prenatal cocaine
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565499
TI  - Investing in the future.

PMID- 7565500
TI  - Talking to your patients about gun violence and gun safety.

PMID- 7565501
TI  - Safe hunting.

PMID- 7565503
TI  - MMA objects to sexual misconduct report.

PMID- 7565502
TI  - The incidence and prevalence of nonfatal gunshot wounds in Minnesota.
AB  - We surveyed a sample of Minnesota hospitals to identify the known incidence of
      nonfatal gunshot wounds (NF-GSW). Only 12 of the 25 hospitals surveyed used E
      codes and were able to retrieve NF-GSW data. Only five hospitals had data dating
      back to 1991. Ninety-two percent of all known NF-GSW (1,425) occurring in
      Minnesota from 1991 to 1994 were recorded at the three Level 1 Trauma Centers
      located in the Twin Cities of Minneapolis and St Paul. The incidence of NF-GSW
      patients admitted to these three trauma centers has increased 20% from 1991 to
      1994. Sixty percent of the NF-GSW treated in Minneapolis involved residents
      living in four zip code areas, comprising 30% of the city's population.
      Recommendations for improved NF-GSW data collection and likely impact on
      prevention are reviewed.

PMID- 7565504
TI  - Report to BMP assails right to due process.

PMID- 7565506
TI  - State housing program recognized.

PMID- 7565505
TI  - Reporting obligations under the Vulnerable Adults Act.

PMID- 7565507
TI  - Taking the helm in turbulent times.

PMID- 7565508
TI  - Kinder, gentler, and lower-paid women physicians.

PMID- 7565509
TI  - Ask the nurse attorney. Who's to blame if the patient's uncooperative?

PMID- 7565510
TI  - Ask the nurse attorney. I am a nurse practitioner and work in an emergency
      setting.

PMID- 7565512
TI  - The new learning environment: fact or fiction?

PMID- 7565513
TI  - A supervisory model of professional competence: a joint service/education
      initiative.
AB  - This article is concerned with describing how a National Health Service (NHS)
      Hospital Trust teamed up with a College of Nursing and Midwifery to develop a
      model of clinical supervision. The article discusses definitions of clinical
      supervision, which were used as a basis for the development of the model;
      identifies the roles and responsibilities of clinical supervisors and describes
      the foundations of an integrated system of educational and professional
      development. The model aims to set standards for clinical competence which
      facilitate continuity in professional development throughout the practitioner's
      career. The collaboration between the two organisations has ensured that the
      model reflects the inter-relationship between theory and practice, thus enhancing
      both academic and professional development. The result is a comprehensive model
      for clinical supervision which encompasses key national initiatives in both
      professional and educational fields; in particular the United Kingdom Central
      Council (UKCC) requirements for continuing registration, maintenance of a
      portfolio of professional development, and continuing education (PREP) and the
      Ten Key Characteristics of the English National Board (ENB) Higher Award. It also
      encourages practitioners to demonstrate good practice through the requirement to
      articulate and enhance professional knowledge using a portfolio, along with a
      system of peer review and defined clinical competencies.

PMID- 7565511
TI  - An ethical dilemma.

PMID- 7565514
TI  - Health and the curriculum: an illuminative evaluation--Part I: Methodology.
AB  - A six-month exploratory study commissioned in 1993 by the English National Board
      for Nursing, Midwifery and Health Visiting (ENB) is described in this two-part
      paper. The research evaluated the integration of a philosophy of health within
      pre- and post-registration curricula in England (Lask et al 1994). In Part I of
      the paper, a philosophy of health as a basis for the curriculum is discussed.
      This is followed by an outline of the project aims, methodology and the
      literature that informed our theoretical understanding of a philosophy of health.
      In Part 2(1) of the paper we present our main findings and discuss their
      implications for professional preparation and continuing education.

PMID- 7565515
TI  - The time commitment of the community nursing services to Project 2000.
AB  - As part of an English National Board funded research study, the authors sent
      questionnaires to 2500 individuals with community nursing qualifications. The
      survey was complemented by a series of interviews with community nurse managers.
      Data indicated that community nurses were spending very considerable amounts of
      time with students. The number of placements provided per year varied
      considerably from one respondent to another, as did the average duration of a
      placement. Community nurses were providing community experience for a variety of
      types of nursing students, as well as students of other professions, and the time
      commitment involved placed them under considerable strain. The authors conclude
      that there is a need to recognise the time given by community nurses to work with
      students, and the resource implications of this commitment.

PMID- 7565516
TI  - Supervising nursing research projects--the case of qualitative research.

PMID- 7565517
TI  - Staff comfort/discomfort with problem-based learning. A preliminary study.
AB  - Crucial to the implementation and success of any educational program, especially
      problem-based learning (PBL), is the support and co-operation from staff involved
      in its use. It is suggested that this support and co-operation is dependent on
      their understanding of and comfort with the process especially when PBL may
      require substantial change in teaching practices. This paper reports the results
      of a pilot survey of staff responses to several aspects of the PBL approach of
      which the authors became aware. The survey focuses on issues of comfort with the
      process, knowledge and understanding of PBL, and preparation for the teaching
      role in PBL. As a preliminary study, it provides some indicators of staff
      responses to PBL implementation as well as highlighting sources of
      comfort/discomfort with the process.

PMID- 7565518
TI  - The development of module evaluation: a Delphi approach.
AB  - This paper outlines an innovatory approach to curriculum evaluation in one of the
      six colleges of nursing that developed an English National Board (ENB) pilot
      scheme in nurse education (ENB 1987a). The method of evaluation is promoted as a
      means of facilitating a working partnership between student and teacher in which
      they can share in the dynamic process of systematic monitoring and reviewing of
      learning programmes to ensure changing needs are met. It is envisaged the
      strategy would interest planners or implementers of health care courses who seek
      a deeper insight into the perceptions and values their learners hold.

PMID- 7565519
TI  - Mentorship: the students' views.
AB  - Whilst the concept of mentorship is not without its critics it is generally
      regarded as a valid way of supporting student nurses. There is much academic
      literature concerning mentorship but little recorded empirical evidence to
      support its use. This study goes some way to correcting this deficit by looking
      at mentorship from the students point of view. Following on from a pilot study 19
      third-year student nurses were asked to complete a 10 item questionnaire
      concerning their experiences of mentorship. Analysis of the data suggested that
      the students found mentorship to be a valid means of support, particularly in the
      early stages of their training. Mentors were seen as fulfilling a socialising
      role as they passed on norms of behaviour and ward routines. Nevertheless, the
      students did not become dependent on their mentors and as training progressed
      they noticed the relationship became more equal. Whilst the varied support
      offered to pre-registration students was seen to be of value, finding an
      acceptable name to describe this eclectic process is problematic, given that the
      support included aspects of preceptorship and clinical supervision as well as
      mentorship.

PMID- 7565520
TI  - Recent cognitive perspectives on learning--implications for nurse education.
AB  - Nurse educators must keep abreast of contemporary learning theory so that their
      teaching reflects current ideas of best practice. In view of this, it is
      important to report on recent developments in the field of learning. Of
      particular significance is the fact that behaviouristic explanations of learning
      have largely been replaced with cognitive perspectives which emphasise the
      complexity of the learning process. Memory, learning, problem solving and
      expertise have all been investigated from a cognitive stance. The highlights of
      this work include, firstly, the portrayal of learning as an active,
      constructivist, cumulative and self-regulated process leading to the development
      of understanding and complex, skilled performance. Secondly, the highly important
      role played by knowledge in learning has been identified and described. Lastly,
      novice-expert differences in problem solving and academic and practical
      performance more generally, are well understood as a result of investigations of
      expertise in many domains. In this paper, these three significant perspectives
      from cognitive psychology will be examined and their implications for the
      education of undergraduate nurses described. Developments in the field of nursing
      that reflect or challenge a cognitive outlook are also identified.

PMID- 7565521
TI  - Creating reality or contributing to confusion? An exploratory study of client
      participation in student learning.
AB  - Changing trends in nurse education continue to highlight the theory-practice gap
      in student preparation. The development of courses such as Project 2000 has
      acknowledged the importance of integrating theory and practice in overcoming this
      phenomenon. As part of this process clients and patients have become more
      involved in student learning, particularly in the community. However
      educationalists and practitioners have expressed concerns about the effect of
      this development on the quality of patient care. Clients have participated
      actively in health visiting education since the 1960s and, as part of a wider
      study, research was undertaken to explore the implications of client
      participation in student learning. A case-study design was developed employing
      qualitative and quantitative methods of data collection, including confidential
      semi-structured interviews. For the purpose of this paper the discussion focuses
      on three major issues; the essential role of clients in the learning process,
      clients' perception of students' role in the practicum, and clients' perception
      of their role in the assessment process. The findings demonstrate that despite
      clients' willingness and commitment to participate in student learning important
      factors must be considered. These include not only the selection of clients,
      detailed briefing of students and clients and careful monitoring of the practice
      situation, but also the preparation of practitioners facilitating student
      learning. These findings are equally important for student learning in pre
      registration programmes.

PMID- 7565522
TI  - The poster assignment: a connected teaching strategy for increasing student
      comfort with issues of sexuality.
AB  - The poster assignment has proven to be the most successful strategy designed by a
      group of nurse educators seeking to facilitate nursing student comfort and
      confidence with sexuality related content. Through the use of a process involving
      both structured and informal interaction opportunities, the context was set for
      students to build knowledge, examine values and attitudes, and develop helping
      skills, necessary building blocks for preparing students to assist patients with
      sexual problems and concerns. The process is described and discussed with
      specific examples given from the authors' experiences with this non-traditional
      learning activity.

PMID- 7565523
TI  - Quality assurance systems for nurse educators.
AB  - This paper seeks to examine two systems designed for thinking about and improving
      the understanding of quality assurance in nurse educator functions, using Total
      Quality Management (TQM) principles. The first system is concerned with what
      needs to be done to realise major goals and objectives. The design parameters,
      adapted from established quality concepts, are those quality characteristics
      specifically associated with nurse educator functions--perceived as a set of
      services. The second system considers how things should be done. How policy
      statements can be translated into specific educator behaviours and practices that
      publicly assert institutional values to student customers within a process of
      continuous quality improvement. Further sections look at the integrated working
      of the systems and discuss system implications. A final summary exhorts nurse
      educators to forge closer working relationships with their student customers to
      fashion a quality service.

PMID- 7565524
TI  - Hyperbilirubinemia and neonatal jaundice.
AB  - Jaundice is a common physiologic problem seen in both term and preterm infants.
      Normal transitional changes in bilirubin metabolism lead to physiological
      jaundice in many infants. In some infants these normal changes at birth may be
      exaggerated, such as occurs with immaturity, or may interact with health
      alterations (pathologic jaundice), resulting in the accumulation of excess
      bilirubin and development of hyperbilirubinemia. Caregivers must appreciate the
      processes and the basis for physiologic jaundice and hyperbilirubinemia and
      recognize infants at risk for these disorders. This article reviews neonatal
      bilirubin metabolism as a basis for understanding the causes and treatment of
      physiologic jaundice and hyperbilirubinemia arising from either physiologic or
      pathologic causes. Patterns of bilirubin in breast fed infants are discussed
      along with other issues related to breast feeding and jaundice. Treatment of
      hyperbilirubinemia and implications for nursing assessment and management of
      infants under phototherapy are also described.

PMID- 7565525
TI  - Latex allergy: an emerging problem in health care.
AB  - Allergy to latex has been increasing as the use of latex products has grown. The
      increase is disproportionately occurring in those people with myelodysplasias,
      those who have undergone multiple surgical procedures, and health care providers.
      Within those groups, the most susceptible to latex allergy are people with other
      allergies. Early identification of high-risk individuals and their avoidance of
      products containing latex can minimize the occurrence of this allergic response.
      Heightened awareness among health care providers is needed because latex is very
      common in hospitals and clinics. Inadvertent exposure places latex-sensitive
      individuals in danger of anaphylaxis. Nurses caring for infants and children are
      able to modify the environment of those at risk for latex allergy, reducing
      exposure to this potentially dangerous substance. Teaching families of children
      at risk will help them avoid latex in the home; many common household substances
      contain latex and are likely to trigger allergic responses.

PMID- 7565526
TI  - Music therapy following suctioning: four case studies.
AB  - This descriptive study evaluates and compares the effectiveness of music,
      presented both aurally and vibrotactilely, in reducing agitation and
      physiological instability following a stress-producing intervention (suctioning)
      in infants with bronchopulmonary dysplasia. Heart rate, oxygen saturation levels,
      level of arousal, stressful facial expressions, and autonomic indicators were
      recorded for each of four preterm infants. All infants experienced a reduction in
      the level of arousal during the taped music intervention when compared with the
      control condition. Three infants spent an increased amount of time in a quiet
      alert state and had improved oxygen saturation levels during the vibrotactile
      intervention. All infants spent more time sleeping during the taped music
      condition than without music or with the vibrotactile intervention. Results
      suggest that music is effective in reducing stress-related behaviors for some
      infants.

PMID- 7565527
TI  - Behaviors of preterm infants with and without chronic lung disease when alone and
      when with nurses.
AB  - Many clinicians believe that infants with chronic lung disease display more
      irritability and react more negatively to care than other preterm infants.
      Therefore, the sleep-wake states and behaviors displayed by 31 high-risk preterm
      infants without chronic lung disease and 20 infants with chronic lung disease
      during four-hour observations conducted in intermediate care between 32 and 36
      weeks postconceptional age were compared. Separate analyses were conducted for
      times when infants were alone and when they were with nurses to determine whether
      behavioral differences might be greater during handling. There were very few
      differences between the groups in either situation. Sleep-wake states did not
      differ. The infants with chronic lung disease exhibited more jitters at every
      age, but only when they were alone. Infants with and without chronic lung disease
      showed isolated differences in five behaviors when they were alone but in only
      two behaviors when they were with nurses. Thus, there is no evidence that 32- to
      36-week preterm infants with chronic lung disease are more irritable or react
      more negatively to care than other preterm infants.

PMID- 7565528
TI  - What happened to the status quo?

PMID- 7565529
TI  - The end of an era.

PMID- 7565530
TI  - The "handy bar": endotracheal tube stabilizing bar.

PMID- 7565531
TI  - Can drug-exposed infants be rocked too much?

PMID- 7565532
TI  - Neonatal hemochromatosis: a case report.
AB  - Hemochromatosis is the excess accumulation of iron in tissue affecting a variety
      of organ systems leading to hepatic fibrosis and multiorgan system failure. When
      excess iron accumulation occurs in utero, as with neonatal hemochromatosis, the
      infant may be stillborn or present with advanced, overwhelming liver disease.
      Hepatic failure in the newborn encompasses a wide variety of disease entities,
      and formulation of a differential diagnosis presents a challenge for the
      clinician. This article reviews one case of neonatal hemochromatosis that was
      diagnosed and successfully treated. Iron metabolism and overload are discussed,
      as well as clinical manifestations, current treatment, and the potential for
      prenatal diagnosis in the future.

PMID- 7565533
TI  - Private practice in Missouri: a CNS perspective.

PMID- 7565534
TI  - Development and validation of the Jenkins' Parent Apprehension Scale.

PMID- 7565535
TI  - Advanced practice nurses and managed care.

PMID- 7565536
TI  - Fewer nurses to answer the buzzer.

PMID- 7565537
TI  - Summary of notifiable diseases, United States 1994.

PMID- 7565538
TI  - Assessing the effectiveness of disease and injury prevention programs: costs and
      consequences.
AB  - Because resources are finite, public health decision makers need to consider the
      costs and effectiveness of alternative prevention strategies. A simplified
      approach to performing marginal cost-effectiveness analyses requires a) a
      description of the program, b) a description of the health outcomes averted and
      the timing of those events, c) the rates of the health outcome, d) the
      preventable fraction of the health outcomes averted, e) the costs per unit of the
      intervention, and f) the direct medical costs of the health outcome prevented and
      the side effects incurred. With this information, the marginal cost-effectiveness
      of an intervention can be determined and applied for decision making.

PMID- 7565539
TI  - Essential components of a tuberculosis prevention and control program.
      Recommendations of the Advisory Council for the Elimination of Tuberculosis.
AB  - Tuberculosis (TB) rates declined steadily for decades in the United States, but
      several complex social and medical factors caused TB morbidity to increase 14%
      from 1985 through 1993. The recent increases in TB morbidity have placed
      additional demands on state and local TB control programs, which already had been
      substantially weakened by inadequate staffing and funding support. TB programs
      throughout the nation must be revitalized if they are to provide core TB control
      activities that enable effective responses to this public health challenge. This
      report describes a model for TB control programs and the essential components of
      a successful TB control program, including three priority strategies for TB
      prevention and control: a) identifying and treating persons who have active TB,
      b) finding and screening persons who have had contact with TB patients to
      determine whether they are infected with Mycobacterium tuberculosis or have
      active TB and providing appropriate treatment, and c) screening populations at
      high risk for TB infection and the development of TB disease to detect infected
      persons and providing therapy to prevent progression to active TB. State and
      local health departments have primary responsibility for preventing and
      controlling TB. To meet this challenge successfully, TB control programs should
      be able to administer activities that include the following core components:
      conducting overall planning and development of policy, identifying persons who
      have clinically active TB, managing persons who have or who are suspected of
      having disease, identifying and managing persons infected with M. tuberculosis,
      providing laboratory and diagnostic services, collecting and analyzing data, and
      providing training and education. The Advisory Council for the Elimination of
      Tuberculosis has prepared this report to provide a national standard by which
      policymakers, TB control program managers, and others evaluating TB programs can
      assess individual TB control programs. The report may also help local programs to
      obtain and maintain adequate resources for TB control activities. In addition to
      defining the essential components of a TB control program, this report emphasizes
      the importance of a) prioritizing TB control activities; b) coordinating care
      with other health-care providers, facilities, and community organizations; c)
      using alternative approaches to TB control (e.g., the expanded use of directly
      observed therapy); d) targeting screening and prevention programs to high-risk
      populations; and e) following current recommendations for the treatment of TB. TB
      control program managers should make every effort to incorporate each of these
      components into their program activities. TB programs may perform these
      activities directly, or programs may coordinate with other providers to ensure
      the implementation of these activities. TB programs may perform these activities
      directly, or programs may coordinate with other providers to ensure the
      implementation of these activities. Failure to meet these core standards can
      decrease a TB program's effectiveness in controlling this reemergent public
      health risk.

PMID- 7565540
TI  - Screening for tuberculosis and tuberculosis infection in high-risk populations.
      Recommendations of the Advisory Council for the Elimination of Tuberculosis.
AB  - This report from the Advisory Council for the Elimination of Tuberculosis updates
      and replaces previous recommendations for screening for tuberculosis (TB) and TB
      infection among high-risk populations. {MMWR 1990;39(No. RR-8):1-7}. In
      particular, these recommendations a) emphasize that screening for TB infection
      should not be given preference over high priority TB prevention and control
      activities, especially identifying and completely treating all persons who have
      active TB as well as conducting prompt, effective contact investigation; b)
      provide more detailed recommendations for screening specific high-risk groups; c)
      provide a detailed description of the tuberculin skin test; and d) revise CDC's
      previous recommendations regarding anergy testing. This report is for public
      health policymakers, administrators, program directors and managers as well as
      health-care providers and others who provide care or services to persons at
      increased risk for TB infection and disease.

PMID- 7565541
TI  - Recommendations for preventing the spread of vancomycin resistance.
      Recommendations of the Hospital Infection Control Practices Advisory Committee
      (HICPAC).
AB  - Since 1989, a rapid increase in the incidence of infection and colonization with
      vancomycin-resistant enterococci (VRE) has been reported by U.S. hospitals. This
      increase poses important problems, including a) the lack of available
      antimicrobial therapy for VRE infections, because most VRE are also resistant to
      drugs previously used to treat such infections (e.g., aminoglycosides and
      ampicillin), and b) the possibility that the vancomycin-resistant genes present
      in VRE can be transferred to other gram-positive microorganisms (e.g.,
      Staphylococcus aureus). An increased risk for VRE infection and colonization has
      been associated with previous vancomycin and/or multiantimicrobial therapy,
      severe underlying disease or immunosuppression, and intraabdominal surgery.
      Because enterococci can be found in the normal gastrointestinal and female
      genital tracts, most enterococcal infections have been attributed to endogenous
      sources within the individual patient. However, recent reports of outbreaks and
      endemic infections caused by enterococci, including VRE, have indicated that
      patient-to-patient transmission of the microorganisms can occur either through
      direct contact or through indirect contact via a) the hands of personnel or b)
      contaminated patient-care equipment or environmental surfaces. This report
      presents recommendations of the Hospital Infection Control Practices Advisory
      Committee for preventing and controlling the spread of vancomycin resistance,
      with a special focus on VRE. Preventing and controlling the spread of vancomycin
      resistance will require coordinated, concerted efforts from all involved hospital
      departments and can be achieved only if each of the following elements is
      addressed: a) prudent vancomycin use by clinicians, b) education of hospital
      staff regarding the problem of vancomycin resistance, c) early detection and
      prompt reporting of vancomycin resistance in enterococci and other gram-positive
      microorganisms by the hospital microbiology laboratory, and d) immediate
      implementation of appropriate infection-control measures to prevent person-to
      person transmission of VRE.

PMID- 7565542
TI  - Engineering and administrative recommendations for water fluoridation, 1995.
      Centers for Disease Control and Prevention.

PMID- 7565543
TI  - 1995 revised guidelines for prophylaxis against Pneumocystis carinii pneumonia
      for children infected with or perinatally exposed to human immunodeficiency
      virus. National Pediatric and Family HIV Resource Center and National Center for
      Infectious Diseases, Centers for Disease Control and Prevention.
AB  - Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection
      in children who have acquired immunodeficiency syndrome (AIDS). Despite the
      publication of guidelines for prophylaxis against PCP for children infected with
      human immunodeficiency virus (HIV) in 1991 (1), ongoing AIDS surveillance has
      detected no substantial decrease in PCP incidence among HIV-infected infants.
      Studies indicate that this continued incidence is associated with failure to
      identify HIV-infected children before PCP occurs and with limitations in the
      ability of CD4+ measurements to identify children at risk for PCP. In March 1994,
      the National Pediatric & Family HIV Resource Center, in collaboration with CDC,
      convened a working group to review additional data about the occurrence of PCP
      among HIV-infected children and to reevaluate the 1991 PCP prophylaxis guidelines
      for children. This report summarizes these new data and presents revised PCP
      prevention guidelines that recommend a) promptly identifying children born to HIV
      infected women and initiating regular diagnostic and immunologic monitoring of
      such children; b) beginning PCP prophylaxis at 4-6 weeks of age for all children
      who have been perinatally exposed to HIV; c) continuing prophylaxis through 12
      months of age for HIV-infected children; and d) making decisions regarding
      prophylaxis for HIV-infected children > or = 12 months of age based on CD4+
      measurements and whether PCP previously has occurred.

PMID- 7565544
TI  - Recommended childhood immunization schedule--United States, 1995. Centers for
      Disease Control and Prevention.
AB  - The need for a single childhood immunization schedule prompted the unification of
      previous vaccine recommendations made by the American Academy of Pediatrics (AAP)
      and the Advisory Committee on Immunization Practices (ACIP). In addition to
      presenting the newly recommended schedule for the administration of vaccines
      during childhood, this report addresses the previous differences between the AAP
      and ACIP childhood vaccination schedules and the rationale for changing previous
      recommendations.

PMID- 7565545
TI  - Assessing the public health threat associated with waterborne cryptosporidiosis:
      report of a workshop.
AB  - In September 1994, CDC convened a meeting to address the public health threat
      associated with waterborne cryptosporidiosis. Representatives from 40 states and
      from regulatory and public health agencies, water utility companies, and advocacy
      groups discussed approaches to avoiding unnecessary boil-water advisories (i.e.,
      statements to the public advising persons to boil water before drinking it) and
      preventing and controlling waterborne cryptosporidiosis. Work groups at the
      meeting addressed four issues: 1) surveillance systems and epidemiologic study
      designs; 2) public health responses when oocysts are detected in drinking water;
      3) cryptosporidiosis in immunocompromised persons; and 4) water sampling methods
      and interpretation of results. The work groups defined the problems associated
      with these issues and developed strategies that could be used initially to manage
      these problems. The work group discussions were summarized, and the conclusions
      were provided as either a) summaries of current knowledge concerning that issue
      or b) suggested ways to obtain the information needed to develop useful
      recommendations. The work group conclusions are for consideration by persons and
      organizations who must assist with these issues and by those who seek to advance
      understanding of waterborne cryptosporidiosis.

PMID- 7565546
TI  - U.S. Public Health Service recommendations for human immunodeficiency virus
      counseling and voluntary testing for pregnant women.
AB  - These recommendations were developed by the U.S. Public Health Service to address
      the increasing epidemic of human immunodeficiency virus (HIV) infection among
      women and their infants. The recommendations stress the importance of early
      diagnosis of HIV infection for the health of both women and their infants and are
      based on advances made in HIV-related treatment and prevention. The most
      significant advance for this population has been the results from a placebo
      controlled, clinical trial that indicated that administration of zidovudine to
      HIV-infected pregnant women and their newborns reduced the risk for perinatal
      transmission of HIV by approximately two thirds (1). This document recommends
      routine HIV counseling and voluntary testing for all pregnant women and is
      intended to serve as guidance for health-care providers in educating women about
      the importance of knowing their HIV infection status. For uninfected women, such
      HIV counseling and testing programs can provide information that can reduce their
      risk for acquiring HIV; for women who have HIV infection, these programs can
      enable them to receive appropriate and timely medical interventions for their own
      health and for reducing the risk for perinatal (i.e., mother to infant) and other
      modes of HIV transmission. These programs also can facilitate appropriate follow
      up care and services for HIV-infected women, their infants, and other family
      members.

PMID- 7565547
TI  - USPHS/IDSA guidelines for the prevention of opportunistic infections in persons
      infected with human immunodeficiency virus: a summary.

PMID- 7565548
TI  - Chorionic villus sampling and amniocentesis: recommendations for prenatal
      counseling. Centers for Disease Control and Prevention.
AB  - Chorionic villus sampling (CVS) and amniocentesis are prenatal diagnostic
      procedures that are performed to detect fetal abnormalities. In 1991, concerns
      about the relative safety of these procedures arose after reports were published
      that described a possible association between CVS and birth defects in infants.
      Subsequent studies support the hypothesis that CVS can cause transverse limb
      deficiencies. Following CVS, rates of these defects, estimated to be 0.03%-0.10%
      (1/3,000-1/1,000), generally have been increased over background rates. Rates and
      severity of limb deficiencies are associated with the timing of CVS; most of the
      birth defects reported after procedures that were performed at > or = 70 days'
      gestation were limited to the fingers or toes. The risk for either digital or
      limb deficiency after CVS is only one of several important factors that must be
      considered in making complex and personal decisions about prenatal testing. For
      example, CVS is generally done earlier in pregnancy than amniocentesis and is
      particularly advantageous for detecting certain genetic conditions. Another
      important factor is the risk for miscarriage, which has been attributed to 0.5%
      1.0% of CVS procedures and 0.25%-0.50% of amniocentesis procedures. Prospective
      parents considering the use of either CVS or amniocentesis should be counseled
      about the benefits and risks of these procedures. The counselor should also
      discuss both the mother's and father's risk(s) for transmitting genetic
      abnormalities to the fetus.

PMID- 7565549
TI  - Venezuelan equine encephalitis--Colombia, 1995.
AB  - An outbreak of Venezuelan equine encephalitis (VEE) that began in northwestern
      Venezuela in April 1995 has spread westward to the Guajira peninsula and to
      Colombia (Figure 1), resulting in an estimated minimum of 13,000 cases in humans
      and an undetermined number of equine deaths. Governments of both countries have
      initiated efforts to control the spread of this outbreak by quarantining and
      vaccinating equines and applying insecticides. This report summarizes the ongoing
      investigation of the outbreak in Colombia.

PMID- 7565550
TI  - Outbreak of gastrointestinal illness associated with consumption of seaweed-
      Hawaii, 1994.
AB  - Seaweed is frequently served as a side dish at meals in the Pacific Islands and
      is a common component in the diet of many persons living in the Pacific Rim.
      Seaweed is often harvested at beaches, gathered in nearshore waters, or purchased
      at local markets. It is served either raw or cooked and is commonly prepared with
      salt and/or other spices and herbs (e.g., chili pepper, ginger, and garlic).
      Previous reports have documented a toxic illness associated with seaweed
      harvested in some locations in the Pacific (1,2). This report summarizes the
      investigation of an outbreak of acute gastrointestinal illness associated with
      consumption of seaweed during a picnic in Hawaii in September 1994.

PMID- 7565551
TI  - Acute lower respiratory tract illness in illicit drug users--South Carolina,
      1995.
AB  - On July 31, 1995, the South Carolina Department of Health and Environmental
      Control was notified of a cluster of five patients with acute, severe lower
      respiratory illnesses among previously healthy residents of a small rural
      community in Berkeley County (1990 population: 128,776). All five patients were
      users of illicit drugs. This report summarizes the preliminary findings of an
      investigation initiated to describe the clinical features and epidemiology of
      this syndrome and to determine an etiology. Based on information about the five
      cases obtained from interviews with the patients and reviews of records, a case
      was defined as an unexplained acute, severe respiratory illness in a previously
      healthy person aged < 65 years characterized by shortness of breath and/or
      pleuritic pain with onset of symptoms during July 15-31. One additional case was
      identified by contacting local physicians, intensive-care units, and pulmonary
      and infectious disease specialists. No cases of similar acute respiratory illness
      were noted in household contacts of patients.

PMID- 7565552
TI  - Patterns of homicide--Cali, Colombia, 1993-1994.
AB  - In Colombia, as in the United States, homicide occurs disproportionately among
      urban residents (1,2). Homicide rates in the city of Cali, Colombia (1994
      population: 1,776,436), increased fivefold from 1985 through 1992, reaching
      levels of 100 per 100,000 persons. Because of this increase, in 1992 the city of
      Cali established the Development, Security, and Peace Program (DESEPAZ) to
      implement a series of strategies to prevent violence and improve security among
      the residents of Cali. An important element of this program was the establishment
      of a surveillance system to enable characterization of patterns and determinants
      of homicide to provide information to decision makers for formulating policies
      and programs. This report summarizes findings from this system for January 1993
      May 1994.

PMID- 7565553
TI  - National surveillance for infectious diseases, 1995.

PMID- 7565554
TI  - Increasing pneumococcal vaccination rates among patients of a National Health
      Care Alliance--United States, 1993.
AB  - Streptococcus pneumoniae is the most common cause of bacterial pneumonia
      worldwide and a leading cause of sepsis and meningitis. In the United States, an
      estimated 40,000 persons die each year from pneumococcal infections. Since 1983,
      23-valent pneumococcal polysaccharide vaccines have been licensed in the United
      States and are 56%-57% effective in preventing invasive pneumococcal disease.
      However, the 1993 National Health Interview Survey documented that < or = 28% of
      persons in high-risk categories, including all persons aged > or = 65 years,
      reported ever having received the vaccine. During 1993-1994, VHA Inc. (Irving,
      Texas)--a national health-care alliance serving approximately 1200 health-care
      organizations nationwide (including 21% of all community hospitals in the United
      States)--initiated efforts to improve pneumococcal vaccine delivery to and
      coverage among patients at increased risk for complications of pneumococcal
      infection. This report summarizes the program and an evaluation of its
      effectiveness in increasing vaccine coverage.

PMID- 7565555
TI  - Increasing influenza vaccination rates for Medicare beneficiaries--Montana and
      Wyoming, 1994.
AB  - Approximately 20,000 influenza-associated deaths occurred during each of 10
      different epidemics in the United States during 1972-1991; most (> 90%) of the
      deaths attributed to pneumonia and influenza occurred among persons aged > or =
      65 years. Although Medicare has provided reimbursement for influenza vaccination
      since 1993, the Health Care Financing Administration (HCFA) received billing
      claims for influenza vaccination for the 1993-94 and 1994-95 influenza seasons
      for only 35% and 38% of Medicare beneficiaries, respectively (HCFA, unpublished
      data, 1995). This report describes the impact of an intervention project in
      September 1994 in which individual Medicare beneficiaries aged > or = 65 years in
      Montana and Wyoming were contacted and encouraged to receive influenza
      vaccination.

PMID- 7565556
TI  - Knowledge, attitudes, and practices of physicians regarding urinary incontinence
      in persons aged > or = 65 years--Massachusetts and Oklahoma, 1993.
AB  - Urinary incontinence (UI)--the involuntary loss of urine sufficient to be a
      problem for the patient or caregivers--affects an estimated 15%-30% of persons
      aged > or = 60 years in the United States and is a major cause of admittance to
      nursing homes. UI may be associated with a variety of medical (e.g., rashes, skin
      infections, pressure sores, urinary tract infections, and falls) and psychosocial
      problems (e.g., depression, embarrassment, restricted social interaction, reduced
      activities outside the home, reduced sexual activity, and sleep disturbances).
      Despite the dissemination of clinical practice guidelines for UI by the Agency
      for Health Care Policy and Research (AHCPR), many physicians do not know how to
      diagnose or treat UI. Beginning in 1992, CDC and AHCPR funded demonstration
      projects in Massachusetts and Oklahoma to educate the public, patients, and
      health-care professionals about UI. In both projects, physicians were assessed
      regarding baseline attitudes toward UI, knowledge of the causes and treatment of
      UI, preparedness to evaluate and treat UI, and current practices regarding UI.
      This report summarizes findings from the two projects during 1993.

PMID- 7565557
TI  - Mammography use--Wisconsin, 1980-1993.
AB  - In the United States, efforts to reduce mortality from breast cancer focus
      primarily on secondary prevention (i.e., early detection and treatment). Since
      1980, private, public, and voluntary organizations in Wisconsin have promoted
      screening mammography as a means for reducing the death rate from breast cancer.
      To assess the effectiveness of these efforts, the Division of Health, Wisconsin
      Department of Health and Social Services (DOH), analyzed data from annual
      statewide surveys of mammography providers during 1989-1993 and data about self
      reported mammography use from the Behavioral Risk Factor Surveillance System
      (BRFSS) during 1987-1993. This report summarizes these analyses and trends in the
      number of mammograms performed annually in Wisconsin during 1980-1993.

PMID- 7565558
TI  - Fluoroquinolone resistance in Neisseria gonorrhoeae--Colorado and Washington,
      1995.
AB  - The fluoroquinolones ciprofloxacin and ofloxacin are among the antimicrobial
      agents recommended by CDC for treating gonorrhea (1). In the United States,
      decreased susceptibility or resistance of strains of Neisseria gonorrhoeae to the
      fluoroquinolones has been reported only sporadically, and treatment failure
      associated with in vitro resistance has not been described (2). However, the
      recent occurrence of resistant cases in Denver and Seattle suggests that
      clinically important resistance to the fluoroquinolones may be emerging. This
      report describes the findings of the investigations of these cases.

PMID- 7565559
TI  - Unintentional carbon monoxide poisonings in residential settings--Connecticut,
      November 1993-March 1994.
AB  - Carbon monoxide (CO) gas is an environmental hazard, and unintentional CO
      poisonings have occurred in multiple settings, including residences, motor
      vehicles, and workplaces. In 1993, exposure to CO produced by a malfunctioning
      natural gas furnace in a Suffield, Connecticut, home resulted in the deaths of
      three children and hospitalization of four other family members. Publicity
      resulting from this and other CO poisoning incidents prompted concern that gas
      furnaces have been a primary cause of residential CO poisonings in Connecticut.
      To determine the sources of residential CO poisonings in Connecticut, the
      Connecticut Department of Public Health (CDPH) surveyed persons with cases of CO
      poisoning during November 1993-March 1994. This report presents the survey
      findings.

PMID- 7565560
TI  - HIV risk practices of male injecting-drug users who have sex with men--Dallas,
      Denver, and Long Beach, 1991-1994.
AB  - As of June 1995, a total of 31,024 cases of acquired immunodeficiency syndrome
      (AIDS) had been reported in the United States among male injecting-drug users
      (IDUs) who also reported sexual contact with other men (1). Although male IDUs
      who report male sex partners have accounted for 7% of all AIDS cases and for 21%
      of cases reported among IDUs, the characteristics and risk practices of male IDUs
      who have sex with men (MSM) have not been clearly determined (2-4). To better
      characterize this group of men with multiple risk factors for human
      immunodeficiency virus (HIV) infection, data collected during February 1991
      through June 1994 from three sites--Dallas; Denver; and Long Beach, California-
      were analyzed as part of the CDC-sponsored AIDS Community Demonstration Projects
      (5,6). This report summarizes results of that analysis.

PMID- 7565561
TI  - Update: Venezuelan equine encephalitis--Colombia, 1995.
AB  - During September 1-October 12, 1995, a total of 12,403 patient visits for
      Venezuelan equine encephalitis (VEE) were reported from La Guajira state,
      Colombia. The actual number of incident cases, estimated from epidemiologic
      surveys, may exceed 45,000. This report updates the ongoing investigation of this
      outbreak (1).

PMID- 7565563
TI  - Outbreak of Salmonellosis associated with beef jerky--New Mexico, 1995.
AB  - In February 1995, the New Mexico Department of Health (NMDOH) was notified of
      cases of salmonellosis in two persons who had eaten beef jerky. An investigation
      by the New Mexico Environment Department determined that these cases were
      associated with beef jerky processed at a local plant. An investigation by NMDOH
      identified 91 additional cases. This report summarizes the investigation of this
      outbreak.

PMID- 7565562
TI  - Use of mammography services by women aged > or = 65 years enrolled in Medicare-
      United States, 1991-1993.
AB  - The incidence of invasive breast cancer among women aged > or = 65 years is twice
      that among those aged 35-44 years (1), and the death rate from breast cancer is
      approximately three times higher among women aged > or = 65 years than among
      women aged 35-64 years (2). Although routine screening mammography among women
      aged > or = 50 years can reduce breast cancer mortality by > or = 30% by
      detecting tumors at early, more treatable stages (3), older women are less likely
      to receive screening mammograms (4). The Health Care Financing Administration
      (HCFA) routinely examines trends in the use of health services by age, race, and
      sex to monitor access to medical care for Medicare beneficiaries. Using Medicare
      claims data, HCFA estimated rates of mammography use among women aged > or = 65
      years during 1991-1993. This report presents the findings of this analysis.

PMID- 7565564
TI  - Blood lead levels among children--Rhode Island, 1993-1995.
AB  - Since January 1993, screening of children aged < 6 years for elevated blood lead
      levels (BLLs) has been mandatory in Rhode Island. Erythrocyte protoporphyrin was
      eliminated as a method of lead screening in February 1993; since then, all
      children in the state have been screened for lead poisoning by testing capillary
      or venous blood samples for lead. From March 1993 through February 1995, results
      of blood lead tests of 56,379 children aged < 6 years were reported to Rhode
      Island's lead surveillance system. This report summarizes an analysis of these
      data by the Rhode Island Department of Health (RIDH) to better characterize the
      burden of childhood lead poisoning in the state.

PMID- 7565565
TI  - Progress toward poliomyelitis eradication--south east Asia region, 1988-1994.
AB  - Since the adoption of the poliomyelitis eradication initiative by the World
      Health Organization (WHO) in 1988, substantial progress toward the eradication of
      polio has been achieved in the Region of the Americas and in the Western Pacific
      Region of WHO (1-3). A major step toward global eradication was made in 1994,
      when polio eradication activities--specifically the implementation of biannual
      National Immunization Days (NIDs)--were accelerated in the member countries of
      the South East Asia Region (SEAR) of WHO. In August 1994, Thailand became the
      first SEAR country to conduct NIDs; by February 1996, seven of the 10 member
      countries will have conducted NIDs. This report summarizes progress toward the
      eradication of polio in SEAR countries from 1988 though 1994 and is based on data
      reported through June 1995.

PMID- 7565566
TI  - Adult blood lead epidemiology and surveillance--United States, second quarter,
      1995.
AB  - CDC's National Institute for Occupational Safety and Health (NIOSH) Adult Blood
      Lead Epidemiology and Surveillance program (ABLES) monitors elevated blood lead
      levels (BLLs) among adults in the United States (1). Twenty-three states,
      representing 64% of the U.S. population, report BLL surveillance results to
      ABLES. This report presents data from ABLES for the second quarter, 1995.

PMID- 7565567
TI  - Cardiovascular disease risk factors and related preventive health practices among
      adults with and without diabetes--Utah, 1988-1993.
AB  - The risk for cardiovascular disease (CVD) among persons with diabetes is two to
      three times higher than among persons without diabetes, and CVD accounts for 48%
      of all deaths among persons with diabetes (1,2). To estimate the prevalence of
      CVD risk factors among and related preventive health practices of the adult
      population with diabetes in Utah, the Utah Diabetes Control Program (UDCP)
      previously had relied primarily on data from national surveys. To guide in
      planning and decision-making about future activities of the UDCP and to assess
      CVD-related behaviors and health practices among persons with diabetes, UDCP
      analyzed data from Utah's Behavioral Risk Factor Surveillance System (BRFSS) for
      1988-1993. This report presents the findings of this analysis.

PMID- 7565568
TI  - Progress toward poliomyelitis eradication--eastern Mediterranean region, 1988
      1994.
AB  - In 1988, the Regional Committee of the Eastern Mediterranean Region (EMR) of the
      World Health Organization (WHO) adopted a resolution to eradicate poliomyelitis
      from the region by the year 2000 (1). Since this goal was established,
      substantial progress toward polio eradication has been achieved using three major
      strategies: 1) achieving and maintaining high coverage with at least three doses
      of oral poliovirus vaccine (OPV3); 2) implementing supplementary vaccination
      activities, including National Immunization Days (NIDs), to rapidly interrupt
      poliovirus transmission; and 3) developing sensitive systems of epidemiologic and
      laboratory surveillance, including use of the standard WHO case definition (2).
      This report summarizes progress toward polio eradication in EMR countries from
      1988 through 1994 and is based on reports received through August 1, 1995.

PMID- 7565569
TI  - Hospitalization for epilepsy--United States, 1988-1992.
AB  - Epilepsy is a chronic neurologic condition manifested by repeated unprovoked
      seizures that affects approximately 1% of the U.S. population (1). Although
      effective treatment can prevent seizures in most persons with epilepsy, some
      persons have frequent seizures, which can lead to brain damage, disability, and
      diminished quality of life (2,3). To assist in characterizing the public health
      impact of epilepsy in the United States, CDC analyzed data from the National
      Hospital Discharge Survey (NHDS) for 1988-1992 to estimate the number of
      hospitalizations for which epilepsy was the first-listed diagnosis.

PMID- 7565572
TI  - [Pathogenesis and progression of esophageal cancer].

PMID- 7565570
TI  - Malaria surveillance--United States, 1992.
AB  - PROBLEM/CONDITION: Malaria is caused by one of four species of Plasmodium (i.e.,
      P. falciparum, P. vivax, P. ovale, or P. malariae) and is transmitted by the bite
      of an infective female Anopheles sp. mosquito. Most malaria cases in the United
      States occur among persons who have traveled to areas that have ongoing
      transmission. However, cases are transmitted occasionally through exposure to
      infected blood products, by congenital transmission, or by local mosquito-borne
      transmission. Malaria surveillance is conducted to identify episodes of local
      transmission and to guide prevention recommendations. REPORTING PERIOD COVERED:
      Cases with onset of illness during 1992. DESCRIPTION OF SYSTEM: Malaria cases
      were identified at the local level (i.e., by healthcare providers or through
      laboratory-based surveillance). All suspected cases were confirmed by slide
      diagnosis and then reported to the respective state health department and to CDC.
      RESULTS: CDC received reports of 910 cases of malaria that had onset of symptoms
      during 1992 among persons in the United States and its territories. In
      comparison, 1,046 cases were reported for 1991, representing a decrease of 13% in
      1992. P. vivax, P. falciparum, P. malariae, and P. ovale were identified in 51%,
      33%, 4%, and 3% of cases, respectively. The species was not identified in the
      remaining 9% of cases. The number of reported malaria cases that had been
      acquired in Africa by U.S. civilians decreased 38%, primarily because the number
      of P. falciparum cases declined. Of U.S. civilians whose illnesses were diagnosed
      as malaria, 81% had not taken a chemoprophylactic regimen recommended by CDC.
      Seven patients had acquired their infections in the United States. Seven deaths
      were attributed to malaria. INTERPRETATION: The decrease in the number of P.
      falciparum cases in U.S. civilians could have resulted from a change in travel
      patterns, reporting errors, or increased use of more effective chemoprophylaxis
      regimens. ACTIONS TAKEN: Additional information was obtained concerning the seven
      fatal cases and the seven cases acquired in the United States. Malaria prevention
      guidelines were updated and disseminated to health-care providers. Persons
      traveling to a malaria-endemic area should take the recommended chemoprophylaxis
      regimen and use personal protection measures to prevent mosquito bites. Any
      person who has been to a malarious area and who subsequently develops a fever or
      influenza-like symptoms should seek medical care, which should include a blood
      smear for malaria. The disease can be fatal if not diagnosed and treated at an
      early stage of infection. Recommendations concerning prevention and treatment of
      malaria can be obtained from CDC.

PMID- 7565571
TI  - [Treatment of inflammatory bowel disease. Present and future perspective].

PMID- 7565573
TI  - [Clinical application of adhesion molecules].

PMID- 7565574
TI  - [Mortality after digestive cancer surgery].

PMID- 7565575
TI  - [Mechanism of neoplasm metastasis and treatment strategy].

PMID- 7565576
TI  - [Father of wound debridement--P.J. Desault].

PMID- 7565577
TI  - [Histopathological and immunohistochemical evaluation of lymph node metastasis in
      superficial esophageal cancer--with reference to the expression of E-cadherin and
      alpha-catenin].
AB  - We compared node-negative patients (13 cases) with node-positive patients (17
      cases) with submucosal cancer of the esophagus, to assess the relationship
      between clinicopathological factors and lymph node metastasis. We also
      investigated the expression of E-cadherin, an intercellular adhesion molecule (27
      cases), and alpha-catenin, an undercoat protein of adherence junction (16 cases)
      by immunohistochemical staining to evaluate the association between intercellular
      adhesiveness and lymph node metastasis in superficial esophageal cancer. There
      was no significant difference between the node-negative and node-positive groups
      in other clinicopathological factors and tumor size, while the frequency of
      lymphatic invasion in the node-positive group was statistically higher than that
      in the node-negative group (p < 0.05). The frequency of lymph node metastasis in
      14 cases with preserved expression of E-cadherin was significantly lower than
      that in 13 cases with reduced or negative expression (7.1% vs. 46.2%: p < 0.05).
      Moreover, all three patients with negative expression of alpha-catenin had lymph
      node metastasis, while only one of 13 patients with preserved or reduced
      expression of alpha-catenin had lymph node metastasis (100% vs. 7.7%: p < 0.01).
      In conclusion, we have found that the evaluation of both E-cadherin and alpha
      catenin expression might be of great value in predicting lymph node metastasis in
      superficial esophageal cancer.

PMID- 7565578
TI  - [Free radical generation in electron transport system of mitochondria after cold
      preservation in UW solution].
AB  - In the liver transplantation one of the causes of primary graft nonfunction is
      likely associated with lipid peroxidation at reperfusion after cold preservation.
      In this study, we investigated whether free radicals produced in mitochondrial
      electron transport system would result in lipid peroxidation after cold
      preservation in UW solution. MATERIALS AND METHODS: Under anesthesia, the liver
      of male Wistar rat was flushed via the portal vein with cold Ringer lactate, and
      then placed in 4 degrees C UW solution for 24 hr. After cold preservation, we
      examined mitochondrial respiratory control ratio (RCR), free radicals (O2-) from
      mitochondrial electron transport system by MCLA induced chemiluminescence, and
      lipid peroxidation by chemiluminescence (CL) after reoxygenation. RESULTS: RCR
      gradually decreased up to 24 hr preservation. O2- generation from mitochondrial
      electron transport system was not recognized at any length of the time after cold
      preservation up to 24 hr. At 6 hr, CL values were slightly higher than those of
      the control, but significantly decreased at 24 hr. CONCLUSION: O2(-)-generated in
      electron transport system of mitochondria did not increase with cold preservation
      up to 24 hr, therefore, the radical from mitochondria did not cause a lipid
      peroxidation at reperfusion injury.

PMID- 7565579
TI  - [Primary and experimental study of a new treatment for hepatolithiasis by
      injection of resin in the intrahepatic bile duct].
AB  - In the treatment of hepatolithiasis, it is sometimes difficult to remove the
      stones completely and residual stones are closely related to the prognosis. In
      cases with residual stones, cholangitis frequently recurs and sometimes it causes
      fatal hepatic failure. We postulated that filling the hepatic bile duct with
      resin may be useful for the prevention of the progress of this disease. This
      experiment is the preliminary study on this new treatment for hepatolithiasis.
      After the injection of Neoprene resin into the left intrahepatic bile duct of a
      mongrel dog, histological changes of the liver and biochemical changes in
      peripheral blood were serially analyzed. After six months, the Neoprene plug
      remained in place. In the lobe treated with Neoprene, volume and weight
      decreased, and fibrosis around the bile duct and interlobular connective tissue
      increased, while, the number of hepatocytes was not changed. There was neither
      abscess nor biloma in the liver. Blood analysis revealed only a transitional
      increase of GOT, GPT and ALP. No complication was caused by this treatment. From
      this result, we conclude that this new method may be useful for the treatment of
      hepatolithiasis.

PMID- 7565580
TI  - [The role of emergent endoscopic retrograde pancreatography (ERP): its usefulness
      in the diagnosis of pancreatic injury].
AB  - To determine the therapeutic modalities for pancreatic injury (PI), it is
      important for the pancreatic ductal injury (DI) to be present or not. We
      performed ERPs in 36 patients who had positive findings in physical examinations,
      serum amylase levels and CT within about 13 hours after injury to diagnose the
      DIs early after injury and to avoid negative laparotomy. In 33 successful ERP
      patients (intraoperatively in 3), 22 had PIs (14 DIs) and 11 had non-PIs. Of 14
      patients with DIs, 12 with main DIs and one with branch injury were treated
      surgically. Another patient with branch injury, who was treated conservatively,
      died of the complications of PI. Nineteen patients without DIs, including 8 PIs,
      were treated conservatively or operated for the associated abdominal injuries,
      who had no complications on PIs in the hospital days. Three unsuccessful ERP
      patients, having PIs, were also operated upon. Among 15 patients, including these
      3 patients and 12 treated surgically during the era before introducing ERPs, 2
      (13.3%) negative laparotomies were noted. Among 16 patients, who underwent both
      of ERP and operation, no negative laparotomies were noted. No complications of
      ERPs occurred. In conclusion, ERP is a reliable modality to detect DIs and to
      determine the therapeutic modalities for PIs.

PMID- 7565581
TI  - [Contributions of tumor types and stages on insulin resistance in patients with
      cancer: preliminary report].

PMID- 7565582
TI  - [Mechanism of hyperinsulinemia in gastrectomized patients with oxyhyperglycemia:
      preliminary report].

PMID- 7565583
TI  - [Wild type p53 tumor suppressor gene and apoptosis in thyroid tumors: preliminary
      report].

PMID- 7565584
TI  - [Hepatocyte growth factor(HGF) concentrations in discharge from surgical drains:
      preliminary report].

PMID- 7565586
TI  - Production of waxy (amylose-free) wheats.
AB  - The Waxy (Wx) protein has been identified as granule-bound starch synthase (GBSS;
      EC 24.1.21), which is involved in amylose synthesis in plants. Although common
      wheat (Triticum aestivum L.) has three Wx proteins, "partial waxy mutants"
      lacking one or two of the three proteins have been found. Using such partial waxy
      mutants, tetra- and hexaploid waxy mutants with endosperms that are stained red
      brown by iodine were produced. Both mutants showed loss of Wx protein and
      amylose. This is the first demonstration of genetic modification of wheat starch.

PMID- 7565585
TI  - Cloning, structural analysis and mapping of the mouse selenocysteine
      tRNA([Ser]Sec) gene (Trsp).
AB  - The tRNA([Ser]Sec) molecule mediates the synthesis of selenoproteins by
      incorporating selenocysteine into specific UGA codons upon translation of mRNAs
      that encode selenocysteine-containing proteins. The mouse gene encoding
      tRNA([Ser]Sec) (Trsp) was isolated from a genomic library and sequenced. The
      mouse sequence is colinear with its tRNA product, and contains a C to T
      transition relative to the homologous genes in other vertebrates except rat.
      Transcriptional control motifs found 5' to the tRNA coding region included a TATA
      element, a PSE element and an SPH motif which is associated with an octamer
      motif. A Northern hybridization analysis showed highest expression in the testis,
      followed by thymus, spleen, kidney, ovary, brain, liver, heart and skeletal
      muscle. Surprisingly, the expression level was lowest in embryonic stem cells.
      These results suggest a tissue-specific transcriptional control. Using
      restriction fragment length variants (RFLVs) in interspecific backcross mice
      between Mus musculus (C3H strain) and Mus spretus, the Trsp gene was mapped to
      the proximal region of mouse Chr 7, cosegregating with octamer-binding
      transcription factor-2 (Otf2).

PMID- 7565587
TI  - Regulation of cell wall beta-glucan assembly: PTC1 negatively affects PBS2 action
      in a pathway that includes modulation of EXG1 transcription.
AB  - Analysis of genes involved in yeast cell wall beta-glucan assembly has led to the
      isolation of EXG1, PBS2 and PTC1. EXG1 and PBS2 were isolated as genes that, when
      expressed from multicopy plasmids, led to a dominant killer toxin-resistant
      phenotype. The PTC1 gene was cloned by functional complementation of the
      calcofluor white-hypersensitive mutant cwh47-1. PTC1/CWH47 is the structural gene
      for a type 2C serine/threonine phosphatase, EXG1 codes for an exo-beta-glucanase,
      and PBS2 encodes a MAP kinase kinase in the Pbs2p-Hog1p signal transduction
      pathway. Overexpression of EXG1 on a 2 mu plasmid led to reduction in a cell wall
      beta 1,6-glucan and caused killer resistance in wild type cells; while the exg1
      delta mutant displayed modest increases in killer sensitivity and beta 1,6-glucan
      levels. Disruption of PTC1/CWH47 and overexpression of PBS2 gave rise to similar
      beta-glucan related phenotypes, with higher levels of EXG1 transcription,
      increased exo-beta-glucanase activity, reduced beta 1,6-glucan levels, and
      resistance to killer toxin. Genetic analysis revealed that loss of function of
      the PBS2 gene was epistatic to PTC1/CWH47 disruption, indicating a functional
      role for the Ptc1p/Cwh47p phosphatase in the Pbs2p-Hog1p signal transduction
      pathway. These results suggest that Ptc1p/Cwh47p and Pbs2p play opposing
      regulatory roles in cell wall glucan assembly, and that this is effected in part
      by modulating Exg1p activity.

PMID- 7565589
TI  - QTL analysis of flowering time in Arabidopsis thaliana.
AB  - Quantitative trait loci (QTL) analyses based on restriction fragment length
      polymorphism maps have been used to resolve the genetic control of flowering time
      in a cross between two Arabidopsis thaliana ecotypes H51 and Landsberg erecta,
      differing widely in flowering time. Five quantitative trait loci affecting
      flowering time were identified in this cross (RLN1-5), four of which are located
      in regions containing mutations or loci previously identified as conferring a
      late-flowering phenotype. One of these loci is coincident with the FRI locus
      identified as the major determinant for late flowering and vernalization
      responsiveness in the Arabidopsis ecotype Stockholm. RLN5, which maps to the
      lower half of chromosome five (between markers mi69 and m233), only affected
      flowering time significantly under short day conditions following a vernalization
      period. The late-flowering phenotype of H51 compared to Landsberg erecta was due
      to alleles conferring late flowering at only two of the five loci. At the three
      other loci, H51 possessed alleles conferring early flowering in comparison to
      those of Landsberg erecta. Combinations of alleles conferring early and late
      flowering from both parents accounted for the transgressive segregation of
      flowering time observed within the F2 population. Three QTL, RLN1, RLN2 and RLN3
      displayed significant genotype-by-environment interactions for flowering time. A
      significant interaction between alleles at RLN3 and RLN4 was detected.

PMID- 7565588
TI  - The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of
      Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis.
AB  - Aflatoxins comprise a group of polyketide-derived carcinogenic mycotoxins
      produced by Aspergillus parasiticus and Aspergillus flavus. By transformation
      with a disruption construct, pXX, we disrupted the aflatoxin pathway in A.
      parasiticus SRRC 2043, resulting in the inability of this strain to produce
      aflatoxin intermediates as well as a major yellow pigment in the transformants.
      The disruption was attributed to a single-crossover, homologous integration event
      between pXX and the recipient A. parasiticus genome at a specific locus,
      designated pksA. Sequence analysis suggest that pksA is a homolog of the
      Aspergillus nidulans wA gene, a polyketide synthase gene involved in conidial
      wall pigment biosynthesis. The conserved beta-ketoacyl synthase, acyltransferase
      and acyl carrier-protein domains were present in the deduced amino acid sequence
      of the pksA product. No beta-ketoacyl reductase and enoyl reductase domains were
      found, suggesting that pksA does not encode catalytic activities for processing
      beta-carbon similar to those required for long chain fatty acid synthesis. The
      pksA gene is located in the aflatoxin pathway gene cluster and is linked to the
      nor-1 gene, an aflatoxin pathway gene required for converting norsolorinic acid
      to averantin. These two genes are divergently transcribed from a 1.5 kb
      intergenic region. We propose that pksA is a polyketide synthase gene required
      for the early steps of aflatoxin biosynthesis.

PMID- 7565591
TI  - Gene regulation by antisense RNA in the fission yeast Schizosaccharomyces pombe.
AB  - This report describes experiments designed to demonstrate the suitability of the
      fission yeast Schizosaccharomyces pombe as a host for antisense RNA regulation. A
      lacZ gene-expressing yeast strain was constructed and used as a host for the
      expression of a series of antisense RNAs complementary to various regions of the
      target lacZ mRNA. All lacZ antisense genes were placed under control of the
      thiamine-repressible nmt1 promoter of S. pombe and expressed from episomal
      plasmids. For each antisense plasmid a corresponding sense control plasmid was
      constructed. All lacZ antisense genes were shown to express antisense RNAs of the
      expected size at equivalent steady-state levels. beta-Galactosidase activity in
      transformed cells expressing the long, short 5' or short 3' lacZ antisense RNAs
      was shown to be reduced by 45%, 20%, and 10%, respectively, relative to control
      transformants. Further experiments indicated that antisense RNA regulation in
      this system was conditional and reversible, with the observed reduction of beta
      galactosidase activity being dependent on the transcription of lacZ antisense
      RNA. Our results represent the first successful example of antisense RNA
      regulation of gene expression in yeast and establish S. pombe as an experimental
      model for the biochemical analysis of antisense RNA regulation.

PMID- 7565590
TI  - Insertion mutations at the maize Opaque2 locus induced by transposable element
      families Ac, En/Spm and Bg.
AB  - Eight independently isolated unstable alleles of the Opaque2 (O2) locus were
      analysed genetically and at the DNA level. The whole series of mutations was
      isolated from a maize strain carrying a wild-type O2 allele and the transposable
      element Activator (Ac) at the wx-m7 allele. Previous work with another unstable
      allele of the same series has shown that it was indeed caused by the insertion of
      an Ac element. Unexpectedly, the remaining eight mutations were not caused by the
      designated Ac element, but by other insertions that are structurally similar or
      identical to one of two different autonomous transposable elements. Six mutations
      were caused by the insertion of a transposable element of the Enhancer/Suppressor
      Mutator (En/Spm) family. Two mutations were the result of the insertion of a
      transposable element of the Bergamo (Bg) family. Genetic tests carried out with
      plants carrying the unstable mutations demonstrated that all were caused by the
      insertion of an autonomous transposable element.

PMID- 7565592
TI  - On the mechanism of UV and gamma-ray-induced intrachromosomal recombination in
      yeast cells synchronized in different stages of the cell cycle.
AB  - A genetic system selecting for deletion events (DEL recombination) due to
      intrachromosomal recombination has previously been constructed in the yeast
      Saccharomyces cerevisiae. Intrachromosomal recombination is inducible by chemical
      and physical carcinogens. We wanted to understand better the mechanism of induced
      DEL recombination and to attempt to determine in which phase of the cell cycle
      DEL recombination is inducible. Yeast cells were arrested at specific phases of
      the cell cycle, irradiated with UV or gamma-rays, and assayed for DEL
      recombination and interchromosomal recombination. In addition, the contribution
      of intrachromatid crossing-over to the number of radiation induced DEL
      recombination events was directly investigated at different phases of the cell
      cycle. UV irradiation induced DEL recombination preferentially in S phase, while
      gamma-rays induced DEL recombination in every phase of the cell cycle including
      G1. UV and gamma-radiation induced intrachromatid crossing over preferentially in
      G1, but it accounted at the most for only 14% of the induced DEL recombination
      events. The possibility is discussed that single-strand annealing or one-sided
      invasion events, which can occur in G1 and may be induced by a double-strand
      break intermediate, may be responsible for a large proportion of the induced DEL
      recombination events.

PMID- 7565593
TI  - Molecular and genetic analysis of nitrite reductase co-suppression in transgenic
      tobacco plants.
AB  - Silencing of Nia host genes and transgenes (encoding nitrate reductase) was
      previously achieved by introducing into tobacco plants the tobacco Nia2 cDNA
      cloned downstream of the cauliflower mosaic virus (CaMV) 35S promoter. To check
      whether Nii host genes and transgenes (encoding nitrite reductase, the second
      enzyme of the nitrate assimilation pathway) were also susceptible to silencing, a
      transgene consisting of the tobacco Nii1 gene with two copies of the enhancer of
      the 35S promoter cloned 1 kb upstream of the Nii promoter region was introduced
      into tobacco plants. Among nine independent transformants analysed, two showed
      silencing of Nii host genes and transgenes in some descendants after selfing, but
      never after back-crossing with wild-type plants, suggesting that silencing
      depends on the number of transgene loci and/or on certain allelic or ectopic
      combinations of transgene loci. In one transformant carrying a single transgene
      locus in a homozygous state, silencing was triggered in all progeny plants of
      each generation, 20 to 50 days after germination. Field trial analysis confirmed
      that silencing was not triggered when the transgene locus of this latter line was
      present in a hemizygous state. In addition, it was revealed that silencing can be
      triggered, albeit at low frequency and later during the development, when this
      transgene locus is brought into the presence of a non-allelic transgene locus by
      crossing, suggesting that a homozygous state is not absolutely required.

PMID- 7565594
TI  - Structure, organization and expression of the metallothionein gene family in
      Arabidopsis.
AB  - Metallothioneins (MTs) are cysteine-rich proteins required for heavy metal
      tolerance in animals and fungi. Recent results indicate that plants also possess
      functional metallothionein genes. Here we report the cloning and characterization
      of five metallothionein genes from Arabidopsis thaliana. The position of the
      single intron in each gene is conserved. The proteins encoded by these genes can
      be divided into two groups (MT1 and MT2) based on the presence or absence of a
      central domain separating two cysteine-rich domains. Four of the MT genes (MT1a,
      MT1c, MT2a and MT2b) are transcribed in Arabidopsis. Several lines of evidence
      suggest that the fifth gene, MT1b, is inactive. There is differential regulation
      of the MT gene family. MT1 mRNA is expressed highly in roots, moderately in
      leaves and is barely detected in inflorescences and siliques. MT2a and MT2b mRNAs
      are more abundant in leaves, inflorescences and in roots from mature plants, but
      are also detected in roots of young plants, and in siliques. MT2a mRNA is
      strongly induced in seedlings by CuSO4, whereas MT2b mRNA is relatively abundant
      in this tissue and levels increase only slightly upon exposure to copper. MT1a
      and MT1c are located within 2 kb of each other and have been mapped to chromosome
      I. MT1b and MT2b map to separate loci on chromosome V, and MT2a is located on
      chromosome III. The locations of these MT genes are different from that of CAD1,
      a gene involved in cadmium tolerance in Arabidopsis.

PMID- 7565595
TI  - A binding site for activation by the Bacillus subtilis AhrC protein, a
      repressor/activator of arginine metabolism.
AB  - In Bacillus subtilis, the AhrC protein represses genes encoding enzymes of
      arginine biosynthesis and activates those mediating its catabolism. To determine
      how this repressor also functions as an activator, we attempted to clone
      catabolic genes by searching for insertions of the Tn917-lacZ transposon that
      express AhrC-dependent, arginine-inducible beta-galactosidase activity. One such
      isolate was obtained. The region upstream of lacZ was subcloned in Escherichia
      coli in such a way that it could be replaced in the B. subtilis chromosome after
      appropriate manipulation. Analysis of exonuclease III-derived deletions located
      an AhrC-dependent, arginine-inducible promoter to within a ca. 1.9 kb fragment.
      The sequence revealed: the 3' end of an ORF homologous to gdh genes encoding
      glutamate dehydrogenase, with highest homology to the homologue from Clostridium
      difficile; the 5' end of an ORF homologous to a Saccharomyces cerevisiae gene
      encoding delta 1-pyrroline 5-carboxylate dehydrogenase (P5CDH), an enzyme of
      arginine catabolism; and just upstream of the latter, a sequence with homology to
      known AhrC binding sites in the upstream part of the biosynthetic argCJBD-cpa-F
      cluster. The same region has also been sequenced by others as part of the B.
      subtilis genome sequencing project, revealing that the P5CDH gene is the first in
      a cluster termed rocABC. Restriction fragments containing the putative AhrC
      binding sequence, but not those lacking it, showed retarded electrophoretic
      mobility in the presence of purified AhrC. A 277 bp AhrC-binding fragment also
      showed anomalous mobility in the absence of AhrC, consistent with its being
      intrinsically bent. DNAse I footprinting localized AhrC binding to bp -16/-22 to
      +1 (the transcription startpoint). Such a location for an activator binding site,
      i.e. overlapping the transcription start, is unusual.

PMID- 7565596
TI  - Molecular characterization of the proline-1 (pro-1) locus of Neurospora crassa,
      which encodes delta 1-pyrroline-5-carboxylate reductase.
AB  - delta 1-pyrroline-5-carboxylate reductase (P5CR; [L-proline: NAD(P+) 5
      oxidoreductase]; EC 1.5.1.2) catalyzes the final step in proline biosynthesis. We
      have shown that the proline-1 (pro-1) locus of Neurospora crassa encodes P5CR.
      The pro-1 gene was localized to a 3.2 kb region by complementation of
      (restoration of proline-independent growth to) a proline auxotroph carrying a
      recessive mutation at the pro-1 locus. The nucleotide sequence of this 3.2 kb
      region contains an open reading frame with coding capacity of 311 amino acids.
      The deduced polypeptide shows significant similarity to P5CR amino acid
      sequences. Similarity of N. crassa P5CR is greatest to that of the yeast,
      Saccharomyces cerevisiae, but is also strong to P5CR sequences from archaea,
      eubacteria, plants, and humans. In N. crassa, amino acid imbalance, including
      deficiency or excess of a single amino acid, such as histidine, induces
      expression of many amino acid biosynthetic genes that are under cross-pathway
      control, a general regulatory system analogous to general amino acid control in
      Saccharomyces. Although P5CR catalyzes the only committed step in proline
      biosynthesis, pro-1 expression was unaltered by histidine starvation and
      independent of CPC1, a positively acting transcription factor that mediates cross
      pathway control in N. crassa.

PMID- 7565597
TI  - Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is
      required for normal migration, division, and integrity of nuclei during mitosis.
AB  - This paper describes genes from yeast and mouse with significant sequence
      similarities to a Drosophila gene that encodes the blood cell tumor suppressor
      pendulin. The protein encoded by the yeast gene, Srp1p, and mouse pendulin share
      42% and 51% amino acid identity with Drosophila pendulin, respectively. All three
      proteins consist of 10.5 degenerate tandem repeats of approximately 42 amino
      acids each. Similar repeats occur in a superfamily of proteins that includes the
      Drosophila Armadillo protein. All three proteins contain a consensus sequence for
      a bipartite nuclear localization signal (NLS) in the N-terminal domain, which is
      not part of the repeat structure. Confocal microscopic analysis of yeast cells
      stained with antibodies against Srp1p reveals that this protein is intranuclear
      throughout the cell cycle. Targeted gene disruption shows that SRP1 is an
      essential gene. Despite their sequence similarities, Drosophila and mouse
      pendulin are unable to rescue the lethality of an SRP1 disruption. We demonstrate
      that yeast cells depleted of Srp1p arrest in mitosis with a G2 content of DNA.
      Arrested cells display abnormal structures and orientations of the mitotic
      spindles, aberrant segregation of the chromatin and the nuclei, and threads of
      chromatin emanating from the bulk of nuclear DNA. This phenotype suggests that
      Srp1p is required for the normal function of microtubules and the spindle pole
      bodies, as well as for nuclear integrity. We suggest that Srp1p interacts with
      multiple components of the cell nucleus that are required for mitosis and discuss
      its functional similarities to, and differences from Drosophila pendulin.

PMID- 7565598
TI  - Double-stranded RNA in rice: a novel RNA replicon in plants.
AB  - The entire sequence of 13952 nucleotides of a plasmid-like, double-stranded RNA
      (dsRNA) from rice was assembled from more than 50 independent cDNA clones. The 5'
      non-coding region of the coding (sense) strand spans over 166 nucleotides,
      followed by one long open reading frame (ORF) of 13716 nucleotides that encodes a
      large putative polyprotein of 4572 amino acid residues, and by a 70-nucleotide 3'
      non-coding region. This ORF is apparently the longest reported to date in the
      plant kingdom. Amino acid sequence comparisons revealed that the large putative
      polyprotein includes an RNA helicase-like domain and an RNA-dependent RNA
      polymerase (replicase)-like domain. Comparisons of the amino acid sequences of
      these two domains and of the entire genetic organization of the rice dsRNA with
      those found in potyviruses and the CHV1-713 dsRNA of chestnut blight fungus
      suggest that the rice dsRNA is located evolutionarily between potyviruses and the
      CHV1-713 dsRNA. This plasmid-like dsRNA in rice seems to constitute a novel RNA
      replicon in plants.

PMID- 7565600
TI  - Cloning, mapping and characterization of the Pseudomonas aeruginosa hemL gene.
AB  - The rate-limiting step in the biosynthesis of tetrapyrroles is the formation of 5
      aminolevulinic acid (ALA). In Pseudomonas aeruginosa ALA is synthesized via a two
      step reaction from aminoacylated tRNA(Glu) by the action of glutamyl-tRNA
      reductase and glutamate-1-semialdehyde-2,1-amino mutase. To initiate an
      investigation of the regulation of the second step in ALA formation, the hemL
      gene was cloned from P. aeruginosa by complementation of an Escherichia coli hemL
      mutant. An open reading frame of 1284 bp encoding a protein of 427 amino acids
      with a calculated molecular mass of 45,404 Da was identified. The hemL gene was
      mapped to the SpeI fragment Z and the DpnI fragment J1 of the P. aeruginosa
      chromosome corresponding approximately to min 0.3-0.9. One transcription start
      site was located 280 bp upstream of the translational start site of the hemL
      gene. No classical sigma 70-dependent promoter was detected. Oxygen stress
      induced by the addition of H2O2 to the growth medium led to an approximately 3.5
      fold increase in hemL expression as determined by mRNA dot blot assays. Anaerobic
      denitrifying growth led to a 2-fold stimulation of hemL transcription. Two
      additional open reading frames were detected downstream of the hemL gene. One
      open reading frame (orf1) of 549 bp encodes a protein of 182 amino acids with a
      calculated molecular mass of 19,638 Da.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565599
TI  - A male-specific 3'-UTR regulates the steady-state level of the exuperantia mRNA
      during spermatogenesis in Drosophila.
AB  - The Drosophila exuperantia gene (exu) functions in both oogenesis and
      spermatogenesis. Alternative RNA processing and promoter usage generates sex
      specific transcripts which differ in their 5' and 3' untranslated regions, but
      encode the same predicted protein. We have sequenced the breakpoints of an exu
      allele which is defective in spermatogenesis but functions normally in oogenesis.
      This allele deletes most of the sequence specific to the male 3'-UTR, together
      with some flanking DNA, and causes a reduction in steady-state level of exu mRNA
      in the testis. In addition, we find that a smaller deletion which removes only
      sequence within the male 3'-UTR reduces the steady-state level of the mRNA and
      prevents an exu transgene from rescuing male sterility. Males carrying multiple
      copies of this transgene are fertile, suggesting that the male-specific 3'-UTR
      functions to maintain a proper level of exu product in the germline.

PMID- 7565601
TI  - Defective I elements introduced into Drosophila as transgenes can regulate
      reactivity and prevent I-R hybrid dysgenesis.
AB  - The I-R hybrid dysgenesis syndrome is characterized by a high level of sterility
      and I element transposition, occurring in the female offspring of crosses between
      males of inducer (I) strains, which contain full-length transposable I elements,
      and females of reactive (R) strains, devoid of functional I elements. The
      intensity of the syndrome in the dysgenic cross is essentially dependent on the
      reactivity level of the R females, which is ultimately controlled by still
      unresolved polygenic chromosomal determinants. In the work reported here, we have
      introduced a transposition-defective I element with a 2.6 kb deletion within its
      second open reading frame into a highly reactive R strain, by P-mediated
      transgenesis. We demonstrate that this defective I element gradually alters the
      level of reactivity in the three independent transgenic lines that were obtained,
      over several generations. After > 15 generations, the transgenic Drosophila show
      strongly reduced reactivity, and finally become refractory to hybrid dysgenesis,
      without, however, acquiring the inducer phenotype. Induction of a low reactivity
      level is reversible--reactivity again increases upon transgene removal--and is
      maternally inherited, as observed for the control of reactivity in natural R
      strains. These results demonstrate that defective I elements introduced as single
      copy transgenes can act as regulators of reactivity, and suggest that some of the
      ancestral defective pericentromeric I elements that can be found in all reactive
      strains could be the molecular determinants of reactivity.

PMID- 7565602
TI  - Overproduction of the ATP-dependent nuclease AddAB improves the structural
      stability of a model plasmid system in Bacillus subtilis.
AB  - The effect of the ATP-dependent exonuclease AddAB complex on the structural
      stability of plasmid pGP1 in Bacillus subtilis was studied. Using deletion
      mutagenesis and gene amplification techniques, B. subtilis strains were
      constructed either lacking or overproducing the AddAB complex, a key enzyme in
      homologous recombination. The deletion mutant possessed no residual ATP-dependent
      nuclease activity; in contrast, the nuclease activity was up to 30 times higher
      in lysates of strains carrying multiple copies of the addAB genes in the
      chromosome. Southern blot analyses of these strains indicated that a linear
      relationship exists between the number of chromosomal gene copies and the level
      of AddAB activity. The structural stability of pGP1 was analyzed in the AddAB
      deficient and over-producing backgrounds. Frequencies of deletion formation in
      the plasmid, as monitored by the expression of the pGP1-encoded penP-lacZ fusion
      on media containing X-gal, were shown to be increased at least 25-fold in the
      addAB knock-out mutant, whereas the stability of pGP1 was improved up to 15-fold
      in strains overproducing the AddAB enzyme. A possible explanation for these
      findings is that interactions between AddAB and plasmid molecules prevent the
      formation of secondary structures that constitute potential deletion target
      sites, and thereby enhance the structural stability of plasmids.

PMID- 7565603
TI  - Gene activation by the Escherichia coli positive regulator OmpR: a mutational
      study of the DNA-binding domain of OmpR.
AB  - The Escherichia coli DNA-binding protein, OmpR, is one of the best characterized
      of the bacterial positive regulators that enhance the transcriptional ability of
      RNA polymerase. OmpR, consisting of 239 amino acids, binds to specific sequences
      located upstream of the cognate ompC and ompF promoters. The C-terminal half of
      OmpR, consisting of about 120 amino acids, exhibits an inherent DNA-binding
      ability. To address the issue of DNA binding by OmpR, we selected a set of OmpR
      mutants, each of which has a single amino acid substitution in the C-terminal
      half of OmpR. In particular, we characterized a number of OmpR mutants which are
      defective in DNA binding and thereby result in an OmpF- OmpC phenotype. Among
      them, a putative positive control OmpR mutant was also obtained, which appears to
      be defective in phosphorylation-dependent transcriptional activation, but not in
      DNA binding. These results are discussed with general emphasis on DNA recognition
      by the E. coli family of OmpR-like regulatory proteins.

PMID- 7565604
TI  - A new mobile genetic element in Lactobacillus delbrueckii subsp. bulgaricus.
AB  - A new IS element (ISL3) was discovered in Lactobacillus delbrueckii subsp.
      bulgaricus during the characterization of the linkage relationships between the
      two genes important for milk fermentation, beta-galactosidase (lacZ) and the cell
      wall associated protease (prtP). ISL3 is a 1494 bp element, flanked by 38 bp
      imperfect inverted repeats, and generates an 8 bp target duplication upon
      insertion. It contains one open reading frame, encoding a potential polypeptide
      of 434 amino acids, which shows significant homology (34% identity) to the
      transposase of the Leuconostoc mesenteroides element IS1165. Molecular analysis
      of spontaneous lacZ mutants revealed some strains that had sustained deletions of
      7 to 30 kb in size, centered on and eliminating the copy of ISL3 next to lacZ.
      Other deletion endpoints were identified as located immediately adjacent to ISL3.
      Furthermore, genetic translocations that had occurred via transposition of ISL3
      were observed fortuitously in cultures screened for deletion mutants. ISL3 can be
      found in one to several copies in various strains of L. delbrueckii. However, it
      was not present in other dairy lactic acid bacteria tested.

PMID- 7565605
TI  - DNA supercoiling in a thermotolerant mutant of Escherichia coli.
AB  - A spontaneously occurring, nalidixic acid-resistant (NalR), thermotolerant (T/r)
      mutant of Escherichia coli was isolated. Bacteriophage P1-mediated transduction
      showed that NalR mapped at or near gyr A, one of the two genes encoding DNA
      gyrase. Expression of gyrA+ from a plasmid rendered the mutant sensitive to
      nalidixic acid and to high temperature, the result expected for alleles mapping
      in gyrA. Plasmid linking number measurements, made with DNA from cells grown at
      37 degrees C or shifted to 48 degrees C, revealed that supercoiling was about 12%
      less negative in the T/r mutant than in the parental strain. Each strain
      preferentially expressed two different proteins at 48 degrees C. The genetic and
      supercoiling data indicate that thermotolerance can arise from an alteration in
      DNA gyrase that lowers supercoiling. This eubacterial study, when coupled with
      those of archaebacteria, suggests that DNA relaxation is a general aspect of
      thermotolerance.

PMID- 7565607
TI  - A genetically tagged, defective I element can be complemented by actively
      transposing I factors in the germline of I-R dysgenic females in Drosophila
      melanogaster.
AB  - Non-LTR retrotransposons, also known as LINEs, transpose by reverse transcription
      of an RNA intermediate. Their mechanism of transposition is apparently different
      from that of retrotransposons and similar to that of proviruses of retroviruses.
      The I factor is responsible for the I-R system of hybrid dysgenesis in Drosophila
      melanogaster. Inducer strains contain several functional I factors whereas
      reactive strains do not. Transposition of I factors can be experimentally
      induced: they are stable in inducer strains, but transpose at high frequency in
      the germline of females, known as SF females, produced by crossing reactive
      females and inducer males. We have constructed an I element, called IviP2, marked
      with the vermilion gene, the coding sequence of which was interrupted by an
      intron. Splicing of the intron can only occur in the transcript initiated from
      the I element promoter. Transposed copies expressing a wild-type vermilion
      phenotype were recovered in the germline of SF females in which I factors were
      actively transposing. This indicates that trans-complementation of a defective I
      element, deficient for the second open reading frame, by functional I factors can
      occur in the germline of dysgenic females.

PMID- 7565606
TI  - Characterization of Gandalf, a new inverted-repeat transposable element of
      Drosophila koepferae.
AB  - The cloning and characterization of Gandalf, a new DNA-transposing mobile element
      obtained from the Drosophila koepferae (repleta group) genome is described. A
      fragment of Gandalf was found in a middle repetitive clone that shows variable
      chromosomal localization. Restriction, Southern blot, PCR and sequencing analyses
      have shown that most Gandalf copies are about 1 kb long, are flanked by 12 bp
      inverted terminal repeats and contain subterminal repetitive regions on both
      sides of the element. As with other elements of the DNA-transposing type (known
      as the 'Ac family'), the Gandalf element generates 8 bp direct duplications at
      the insertion point. Coding region analysis has shown that the longer open
      reading frame found in Gandalf copies could encode part of a protein. However,
      whether or not the 1 kb copies of the element are actually the active transposons
      remains to be elucidated. Gandalf shows a very low copy number in D. buzzatii, a
      sibling species of D. koepferae. An attempt to induce interspecific hybrid
      dysgenesis in hybrids of these two species has been unsuccessful.

PMID- 7565608
TI  - Schizosaccharomyces pombe rds1, an adenine-repressible gene regulated by glucose,
      ammonium, phosphate, carbon dioxide and temperature.
AB  - We report the isolation and characterization of an adenine-repressible gene,
      rds1, in the fission yeast Schizosaccharomyces pombe. The transcript of rds1 is
      greatly increased in abundance when adenine auxotrophic strains are starved for
      adenine. rds1 is also derepressed when wild-type cells are starved for glucose,
      ammonium, or phosphate. In addition, derepression occurs when wild-type cells are
      exposed to a carbon dioxide atmosphere, when they are shifted to higher
      temperatures or when they enter stationary phase. The nucleotide sequence of the
      rds1 gene and the corresponding amino acid sequence of its protein share no
      obvious homologies with any other known gene or protein and we have not found a
      phenotype for rds1 disruption mutants. We speculate that expression of the rds1
      gene is regulated by one or several components of the adenine nucleotide pool and
      that its gene product has a function in stress-related responses of the cell.

PMID- 7565609
TI  - The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus
      aureus.
AB  - The synthesis of virulence factors and other exoproteins in Staphylococcus aureus
      is controlled by the global regulator, agr. Expression of secreted proteins is up
      regulated in the postexponential growth phase, whereas expression of surface
      proteins is down-regulated by agr. The agr locus consists of two divergent
      operons, transcribed from neighboring but non-overlapping promoters, P2 and P3.
      The P2 operon sequence, reported here, contains 4 open reading frames, agrA, C,
      D, and B, of which A and C appear to encode proteins of a classical 2-component
      signal transduction pathway. The P3 operon specifies a 0.5 kb transcript, RNA
      III, which is the actual effector of the agr response, and, incidentally, encodes
      the agr-regulated peptide delta-hemolysin. Transcriptional fusions have shown
      that both P2 and P3 are agr sensitive (function in an agr+ but not in an agr-
      background) and deletion analysis has shown that all four of the P2 ORFs are
      involved; agrA and agrC seem to be absolutely required for the transcriptional
      activation of the agr locus, whereas agrB and agrD seem to be partially required.
      Since transcription of P2 requires P2 operon products, the P2 operon is
      autocatalytic, and is thus admirably suited to the need for rapid production of
      exoproteins at a time when overall growth is coming to a halt.

PMID- 7565610
TI  - Analysis of Tn5 inversion events in Escherichia coli plasmids.
AB  - The ability of the bacterial transposon Tn5 to undergo sequence inversion in Rec+
      Escherichia coli cells as a result of recombination between its duplicated IS50
      elements was examined using specially designed plasmid constructs. Surprisingly,
      recombination events in the IS50 elements that led to crossover and therefore Tn5
      inversion could be detected at a frequency of only 10(-5). This was approximately
      an order of magnitude lower than the frequency of IS50 recombination that led to
      conversion events (i.e. non-reciprocal recombination) without crossover, and at
      least two orders of magnitude lower than the frequency of intermolecular
      recombination between IS50 elements on two different plasmids. These rare
      conversion and inversion events in Tn5 appeared to be due to intramolecular
      recombination and not simply to multiple rounds of reciprocal crossing over,
      since the heterodimeric intermediates that would be generated during the latter
      process could be readily isolated but were shown to yield a completely different
      set of plasmid products upon resolution.

PMID- 7565611
TI  - Zeon-1, a member of a new maize retrotransposon family.
AB  - We have previously shown that the tandemly duplicated 27 kDa maize storage
      protein locus underwent mitotic rearrangement to yield a single-copy allele in
      isolates of the inbred line A188. This rearrangement contains a new LTR
      retrotransposon, designated Zeon-1. This middle repetitive element of 7313 bp had
      two long terminal repeats, a primer binding site, a polypurine tract and a gag
      related open reading frame of 375 amino acids. Transcripts of the gag-related
      region were detected by the polymerase chain reaction (PCR) in certain maize
      tissues, and Western blots detected the gag-related protein in the same tissues.
      Moreover, the product of this mitotic rearrangement was shown to contain the same
      insertion site and 3' LTR as Zeon-1, suggesting that this rearrangement occurs
      with unusual precision. Zeon elements were found to be present in teosinte and
      not present in the Gramineae wheat, barley, sorghum and rye.

PMID- 7565612
TI  - The plastid aldolase gene from Chlamydomonas reinhardtii: intron/exon
      organization, evolution, and promoter structure.
AB  - Genomic clones encoding the plastidic fructose-1,6-bisphosphate aldolase of
      Chlamydomonas reinhardtii were isolated and sequenced. The gene contains three
      introns which are located within the coding sequence for the mature protein. No
      introns are located within or near the sequence encoding the transit-peptide, in
      contrast to the genes for plastidic aldolases of higher plants. Neither the
      number nor the positions of the three introns of the C. reinhardtii aldolase gene
      are conserved in the plastidic or cytosolic aldolase genes of higher plants and
      animals. The 5' border sequences of introns in the aldolase gene of C.
      reinhardtii exhibit the conserved plant consensus sequence. The 3' acceptor
      splice sites for introns 1 and 3 show much less similarity to the eukaryotic
      consensus sequences than do those of intron 2. The plastidic aldolase gene has
      two tandemly repeated CAAT box motifs in the promoter region. Genomic Southern
      blots indicate that the gene is encoded by a single locus in the C. reinhardtii
      genome.

PMID- 7565613
TI  - Roa307, a protein encoded on Coxiella burnetii plasmid QpH1, shows homology to
      proteins encoded in the replication origin region of bacterial chromosomes.
AB  - TnphoA mutagenesis identified an open reading frame, roa307, immediately upstream
      of the partition locus qsopAB on the Coxiella burnetii plasmid QpH1. The protein
      sequence deduced from roa307 displayed homology to Orf290 of Pseudomonas putida,
      Orf283 and Orf282 (SpoOJ) of Bacillus subtilis-hypothetical products of genes in
      the chromosomal replication origin region. Expression of roa307 was demonstrated
      by PhoA activity of an Roa307-PhoA fusion.

PMID- 7565614
TI  - A fission yeast gene mapping close to suc1 encodes a protein containing two
      bromodomains.
AB  - A novel gene, brd1, has been cloned from the fission yeast Schizosaccharomyces
      pombe. The predicted brd1 product contains two copies of an imperfect repeat of
      96 amino acid residues in its N-terminal half. These each include a region with
      high homology to the bromodomains found in transcriptional activator proteins
      from a diversity of eukaryotes. An in vivo deletion of the complete brd1 open
      reading frame is not lethal but cells exhibit thermosensitivity, with reductions
      in both cell growth and stationary phase survival at 36 degrees C. brd1 maps
      adjacent to the gene suc1, but is expressed separately to give a low abundance
      2.1 kb mRNA.

PMID- 7565616
TI  - The role of conserved leucines in the M2 domain of the acetylcholine receptor in
      channel gating.
AB  - A highly conserved leucine is found in the middle of the porelining (M2) domain
      of the members of the ligand-gated ion channel family. Two very different roles
      have been proposed for this leucine. In one model, this residue swings into the
      lumen of the channel during desensitization to form the nonconducting
      desensitized state, whereas in the other model, the leucines from each subunit
      interact with each other to form a constriction in the channel that constitutes
      the actual gate of the channel. We examined the role of this leucine in the
      muscle-type acetylcholine receptor by replacing it with the polar amino acid
      threonine. Replacement of the leucine in any one subunit slows desensitization
      and shifts the dose-response relationship toward lower concentrations.
      Replacement of leucines in additional subunits leads to progressively larger
      shifts in the dose-response curves. The shift depends only on the number of
      leucines replaced, not on which particular subunits contain the mutation; in
      other words, the mutations act independently. At the single-channel level, the
      mutation greatly increases the channel mean open time. We conclude that the role
      of the conserved leucine is to set the mean open time of the channel through
      interactions with other regions of the receptor rather than to serve as the gate
      per se of the ion channel.

PMID- 7565617
TI  - Rat beta 3 subunits expressed in human embryonic kidney 293 cells form high
      affinity [35S]t-butylbicyclophosphorothionate binding sites modulated by several
      allosteric ligands of gamma-aminobutyric acid type A receptors.
AB  - Human embryonic kidney 293 cells transiently transfected with beta 3 subunits of
      gamma-aminobutyric acid type A receptors from the rat exhibited a specific high
      affinity binding for [35S]t-butylbicyclophosphorothionate (TBPS) that could be
      inhibited by pentobarbital, etazolate, (+)-etomidate, alphaxalone, propofol,
      chlormethiazole, and Ro 5-4864. The potency of these compounds for inhibition of
      [35S]TBPS binding was similar in membranes from beta 3 subunit-transfected human
      embryonic kidney 293 cells and in cerebellar membranes. In contrast to maximally
      inhibiting concentrations of unlabeled TBPS or picrotoxin, which caused a
      monophasic and rather slow dissociation of [35S]TBPS, maximally inhibiting
      concentrations of pentobarbital, etazolate, alphaxalone, propofol,
      chlormethiazole, and Ro 5-4864 accelerated the dissociation of [35S]TBPS from
      beta 3 subunit-containing membranes. Immunoaffinity chromatography and Western
      blot analysis with subunit-specific antibodies indicated that other endogenous
      subunits possibly present in these cells were not associated with beta 3
      subunits. These results appear to indicate that most of the allosteric binding
      sites present on gamma-aminobutyric acid type A receptors can be formed by the
      beta subunit of these receptors. Homo-oligomeric beta 3 receptors therefore are
      an excellent model system for the structural investigation of gamma-aminobutyric
      acid type A receptors.

PMID- 7565615
TI  - A temperature-sensitive lambda cI repressor functions on a modified operator in
      yeast cells by masking the TATA element.
AB  - We describe the construction and analysis of derivatives of the yeast TDH3
      promoter in which the TATA box element has been replaced by a portion of the
      phage lambda operator containing a consensus TATA site flanked by binding sites
      for the cI repressor. Transcription of a reporter gene under the control of such
      a promoter is reduced in cells that express the cI repressor protein. Deletion of
      the native TATA element of the TDH3 promoter reduces transcription to the same
      extent. The cI repressor may act by "masking" the TATA element located between
      the repressor binding sites. Furthermore, the use of a temperature-sensitive cI
      repressor allowed temperature-dependent transcription of the reporter gene.

PMID- 7565618
TI  - Hamster alpha 1B-adrenergic receptor directly activates Gs in the transfected
      Chinese hamster ovary cells.
AB  - A prototypic Ca(2+)-mobilizing hormone receptor, alpha 1-adrenergic receptor
      (alpha 1AR), stimulates cAMP accumulation. The mechanism underlying this
      phenomenon was previously suggested to be secondary to phosphatidylinositol
      hydrolysis-protein kinase C activation in some cells. We transfected Chinese
      hamster ovary (CHO)-K1 cells with hamster alpha(1B)AR cDNA and isolated cells
      stably expressing alpha(1B)AR (CHO alpha 1B cells). We investigated the molecular
      mechanism underlying the alpha 1AR-mediated cAMP production in the CHO alpha 1B
      cells. Norepinephrine (NE) stimulated intracellular calcium mobilization and cAMP
      production through alpha(1B)AR. Pretreatment with a phospholipase C inhibitor, U
      73,122 (10 microM), abolished the NE-induced intracellular calcium response,
      whereas it did not affect the NE-stimulated cAMP production. Treatment with
      various agents (protein kinase C inhibitors, calcium ionophore, cyclo-oxygenase
      inhibitor, or pertussis toxin) had little effect on the NE-induced cAMP
      production. The parent CHO and CHO alpha 1B cells contained similar amounts of Gs
      alpha (42 and 45 kDa, respectively), as detected with immunoblot analysis, and
      exhibited similar extents of cAMP synthesis with cholera toxin and forskolin.
      Adenylyl cyclase activity in the CHO alpha 1B cell membranes was also enhanced by
      NE. Furthermore, incubation of CHO alpha 1B cell membranes with antiserum
      directed against the carboxyl-terminal portion of Gs alpha inhibited the NE
      stimulated adenylyl cyclase activity. Taken together, the results indicate that
      the alpha(1B)AR-mediated cAMP synthesis in CHO alpha 1B cells reflects direct
      stimulation of Gs-adenylyl cyclase. Therefore, the alpha 1AR-stimulated cAMP
      production observed in some native tissues may involve the multiple mechanisms of
      the direct activation of Gs-adenylyl cyclase and a secondary effect through
      activation of phosphatidylinositol hydrolysis.

PMID- 7565619
TI  - Novel steroid 5 alpha-reductase inhibitor FK143: its dual inhibition against the
      two isozymes and its effect on transcription of the isozyme genes.
AB  - Recent cloning of the cDNAs for the two isozymes of steroid 5 alpha-reductase (EC
      1.3.99.5) allowed individual expression of the isozymes and permitted us to
      investigate the action of steroid 5 alpha-reductase inhibitors against the
      individual isozymes without any ambiguity that may be caused by coexistence of
      the isozymes in tissue preparations. We examined the kinetic characteristics of
      FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1- yl]butyric
      acid), a novel nonsteroidal steroid 5 alpha-reductase inhibitor against cloned
      human and rat steroid 5 alpha-reductase isozymes. FK143 was shown to inhibit both
      isozymes equally. The mode of the inhibition of FK143 against both isozymes was
      noncompetitive. The inhibition constants Kie and Kies of FK143 for human types 1
      and 2 were 27.0 and 19.6 nM and 19.9 and 14.5 nM, respectively. Species
      selectivity between human and rat of the inhibitory activity of FK143 against
      both isozymes was not found. We also examined the effect of FK143 on the in vivo
      expression of the genes encoding for the rat steroid 5 alpha-reductase isozymes.
      FK143 reduced the testosterone-induced increase in the amount of the type 1 mRNA
      in castrated rat, whereas it did not substantially affect the amount of the type
      2 mRNA.

PMID- 7565620
TI  - Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in
      distribution and function among species.
AB  - The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac
      motility and in behavioral disorders. Characteristics of 5-HT3Rs appear to be
      heterogeneous among species, but human 5-HT3R cDNA has not been identified. We
      isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has
      been reported to generate two alternative splicing isoforms that differ by six
      amino acids. All of our isolated human clones corresponded to the shorter
      isoform. Amino acid identities with mouse neuroblastoma N1E-115 and rat brain 5
      HT3Rs were 84% for each. Southern blot analysis of human genomic DNA suggested
      that our cloned transcript encoded a human counterpart for the rodent 5-HT3Rs.
      This gene was assigned to chromosome 11 using polymerase chain reaction analysis
      of a human/rodent somatic cell hybrid panel. With the use of Northern blot
      analysis, 5-HT3R transcripts were identified in human small intestine, colon, and
      brain regions including hippocampus, amygdala, and striatum. In human heart, 5
      HT3R expression was not detectable even with reverse transcriptase-polymerase
      chain reaction analysis, although it was detectable in mouse heart. Transfection
      of COS-1 with human 5-HT3R cDNA induced specific binding of the 5-HT3R-selective
      radioligand [3H]YM060. Human 5-HT3R showed typical characteristics of the 5-HT3R,
      but its affinity for the 5-HT3R agonist m-chlorophenylbiguanide was much lower
      than that of rat 5-HT3R. When injected with human 5-HT3R cRNA, the oocytes
      responded to 5-HT3R agonists with a rapidly developing inward current. The
      potency of the agonists to induce inward current paralleled that to compete with
      the radioligand binding, and 2-methyl-5-hydroxytryptamine, a partial agonist for
      mouse 5-HT3R, was a full agonist for human 5-HT3R. Our data revealed that the 5
      HT3R molecule has interspecies differences in both tissue distribution and
      functional profile.

PMID- 7565621
TI  - Substitution at residue 473 confers progesterone 21-hydroxylase activity to
      cytochrome P450 2C2.
AB  - The carboxyl-terminal 28 amino acids of rabbit cytochrome P450 2C2 are markedly
      different from those of other rabbit cytochrome P450 2C family members and,
      substitution of the equivalent amino acids of other cytochrome P450s can confer
      novel steroid hydroxylase activity to P450 2C2 while the normal lauric acid
      hydroxylase activity is retained. To determine the basis for the novel steroid
      hydroxylase activity, amino acids of cytochrome P450 2C1 were substituted for
      those of cytochrome P450 2C2 and the mutants were expressed in COS-1 cells. There
      are 13 differences between the sequences of cytochrome P450 2C2 and P450 2C1 in
      this region, including five nonconservative exchanges of charged and uncharged
      amino acids. However, only substitution of valine for Ser-473 increased steroid
      hydroxylase activity to the maximum level expected in a modified cytochrome P450
      2C2, which contained additional substitutions in the 368-388 region to maximize
      progesterone hydroxylase activity. Introduction of this single substitution into
      cytochrome P450 2C2 resulted in 21-progesterone hydroxylase activity similar to
      that resulting from substitution of all 28 carboxyl-terminal cytochrome P450 2C1
      amino acids. None of the substitutions, with one exception, substantially
      affected either lauric acid hydroxylase activity or the amount of immunologically
      reactive cytochrome P450 that was expressed. A glycine substitution for Val-477
      reduced activity of both lauric acid hydroxylase and progesterone hydroxylase and
      altered the regioselectivity of the hydroxylation for both. Homology modeling of
      cytochrome P450 2C2, based on the cytochrome bacterial P450cam sequence,
      indicated that the side chains of residue 473 and the other five residues
      previously shown to affect substrate specificity face the substrate pocket. For
      four of the six residues, smaller and more hydrophobic residues increased
      progesterone relative to lauric acid hydroxylation.

PMID- 7565622
TI  - Structure-activity relationship of novel pentapeptide neuropeptide Y receptor
      antagonists is consistent with a noncontinuous epitope for ligand-receptor
      binding.
AB  - We report the first systematic study on short peptide structure affinity and
      activity for the neuropeptide Y (NPY) receptor. A series of linear pentapeptides
      has been synthesized that display affinities in the low micromolar range toward
      rat brain NPY receptors. Furthermore, some of these compounds competitively
      antagonize the Y1-type NPY receptor-mediated increase in cytosolic Ca2+ in human
      erythroleukemic (HEL) cells. The inactive NPY carboxyl-terminal pentapeptide (Thr
      Arg-Gln-Arg-Tyr-NH2; IC50 > 100 microM) was modified by replacing threonine with
      an aromatic amino acid and glutamine with leucine. This resulted in a series of
      pentapeptides with dramatically improved affinity (IC50 = 0.5-4 microM) for the
      rat brain receptor. The structure-affinity data suggest that these peptides may
      represent a noncontinuous epitope containing the amino-terminal tyrosine and the
      carboxyl-terminal residues Arg-35 and Tyr-36 of NPY.

PMID- 7565623
TI  - Inhibition of interleukin-1 beta production by SKF86002: evidence of two sites of
      in vitro activity and of a time and system dependence.
AB  - Cytokine-suppressing anti-inflammatory drugs (CSAIDs) are reported to inhibit
      production of proinflammatory cytokines such as interleukin-1 beta (IL-1 beta)
      and tumor necrosis factor-alpha (TNF-alpha) by affecting a stress-induced kinase.
      To gain a better understanding of the selectivity and cellular dynamics of this
      type of inhibitor, we studied in vitro the prototype member of this class of
      agents, SKF86002. Lipopolysaccharide (LPS)-activated human monocytes treated with
      SKF86002 produced less proIL-1 beta but normal amounts of the noncytokine
      lysozyme. Two-dimensional gel analysis indicated that only eight polypeptides
      produced by monocytes were decreased by SKF86002. Inhibition of IL-1 beta
      production was achieved by affecting two separate steps in this cytokine's
      biogenesis. First, SKF86002 lowered proIL-1 beta synthesis. By pulse-chase
      analysis, this effect was localized to a posttranscriptional site of action;
      maximal inhibition was observed when SKF86002 was added at the time of cytokine
      translation. Exposure of monocytes to SKF86002 for > 2 hr led to a loss of IL-1
      beta inhibitory activity, suggesting that these cells adapted to this agent.
      Moreover, LPS-activated monocytes that were pretreated with granulocyte
      macrophage colony-stimulating factor were less sensitive to the proIL-1 beta
      inhibitory effect of SKF86002, and production of proIL-1 beta by cytokine
      stimulated human fibroblasts was impaired only modestly by the CSAID. A second
      effect of SKF86002 was to inhibit release of IL-1 beta into the medium in
      response to high concentrations of LPS; this effect is observed only with freshly
      isolated human monocytes as other IL-1 beta-producing cells do not release
      significant cytokine in response to LPS. The ability of SKF86002 to inhibit this
      posttranslational mechanism was mimicked by lysosomotrophic agents such as
      chloroquine, quinacrine, and methylamine. In contrast, chloroquine, and
      quinacrine were not effective inhibitors of monocyte proIL-1 beta translation.
      Thus, SKF86002 inhibits IL-1 beta production by affecting at least two distinct
      steps in the biosynthesis of this cytokine. Manifestation of these two effects,
      however, is dependent on the length of time for which cells are exposed to this
      agent and the nature of the cytokine-producing cellular system.

PMID- 7565625
TI  - Novel pharmacological properties of transient potassium currents in central
      neurons revealed by N-bromoacetamide and other chemical modifiers.
AB  - The chemical modifiers N-bromoacetamide (NBA), N-bromosuccinimide (NBS), and
      chloramine-T (ChT) are commonly used to remove fast inactivation of sodium
      currents and transient potassium currents (IA). In the present study, I examined
      the effects of these chemical modifiers as well as of others on IA in neurons
      dissociated from several brain regions. External application of NBA irreversibly
      inhibited IA, with higher NBA concentrations increasing the rate of inhibition.
      The current kinetics, however, were not altered by external NBA at any
      concentration. IA was also inhibited by internal NBA but only at high
      concentrations, and the rate of inhibition was much slower. The current kinetics
      were not altered by internal NBA at any concentration. NBA is a nonspecific
      chemical reagent that can modify a protein at several target amino acids. The NBA
      induced irreversible inhibition of IA was reproduced by external
      diethylpyrocarbonate, a reagent that specifically modifies histidine residues,
      and by ChT and cyanogen bromide, reagents that modify methionine residues through
      distinct mechanisms. However, NBS, a reagent that cleaves the peptide bond at
      tryptophan residues, had no effect on IA, nor did chemical modifiers specific for
      cysteine and tyrosine residues. Taken together, these results suggest that the
      conserved, functionally important methionine and/or histidine residues are the
      likely targets for NBA modifications. These novel pharmacological properties are
      in sharp contrast to those known previously, despite their similarity in both
      kinetics and 4-AP sensitivities. Therefore, the pharmacological treatments
      presented in the present study should be useful for characterizing other IA.

PMID- 7565624
TI  - Comparison of the pharmacology and signal transduction of the human cannabinoid
      CB1 and CB2 receptors.
AB  - The recently cloned CB2 cannabinoid receptor subtype was stably transfected into
      AtT-20 and Chinese hamster ovary cells to compare the binding and signal
      transduction properties of this receptor with those of the CB1 receptor subtype.
      The binding of [3H]CP 55,940 to both CB1 and CB2 was of similar high affinity
      (2.6 and 3.7 nM, respectively) and saturable. In competitive binding experiments,
      (-)-delta 9-tetrahydrocannabinol and CP 55,940 were equipotent at the CB1 and CB2
      receptors, but WIN 55212-2 and cannabinol bound with higher affinity to the CB2
      than the CB1 receptor. HU 210 had a higher affinity for the CB1 receptor.
      Anandamide, a recently identified endogenous cannabinoid agonist, was essentially
      equipotent at both receptor subtypes. The structurally related fatty acid
      ethanolamides dihomo-gamma-linolenylethanolamide and mead ethanolamide also bound
      with relatively equal affinity to both receptors, but adrenylethanolamide had a
      higher affinity for the CB1 receptor. The rank order of potency and efficacy for
      binding of the selected agonists to the CB1 and CB2 receptors was mimicked in
      functional inhibition of cAMP accumulation experiments for all compounds tested.
      Both CB1 and CB2 receptors couple to the inhibition of cAMP accumulation that was
      pertussis toxin sensitive. SR141716A, a CB1 receptor antagonist, was a poor
      antagonist at the CB2 receptor in both binding and functional inhibition of cAMP
      accumulation experiments. When expressed in AtT-20 cells, the CB1 receptor
      mediated an inhibition of Q-type calcium channels and an activation of inward
      rectifying potassium channels. In contrast, the CB2 receptor did not modulate the
      activity of either channel under identical assay conditions. Similar to results
      obtained for CB1 receptor, the CB2 receptor did not couple to the activation of
      phospholipases A2, C, or D or to the mobilization of intracellular Ca2+. Except
      for its inability to couple to the modulation of Q-type calcium channels or
      inwardly rectifying potassium channels, the CB1 and CB2 receptors display similar
      pharmacological and biochemical properties.

PMID- 7565626
TI  - Carrier- and receptor-mediated transport of folate antagonists targeting folate
      dependent enzymes: correlates of molecular-structure and biological activity.
AB  - The transport properties and growth-inhibitory potential of 37 classic and novel
      antifolate compounds have been tested in vitro against human and murine cell
      lines expressing different levels of the reduced folate carrier (RFC), the
      membrane-associated folate binding protein (mFBP), or both. The intracellular
      targets of these drugs were dihydrofolate reductase (DHFR), glycinamide
      ribonucleotide transformylase (GARTF), folylpolyglutamate synthetase (FPGS), and
      thymidylate synthase (TS). Parameters that were investigated included the
      affinity of both folate-transport systems for the antifolate drugs, their growth
      inhibitory potential as a function of cellular RFC/mFBP expression, and the
      protective effect of either FA or leucovorin against growth inhibition.
      Methotrexate, aminopterin, N10-propargyl-5,8-dideazafolic acid (CB3717), ZD1694,
      5,8-dideazaisofolic acid (IAHQ), 5,10-dideazatetrahydrofolic acid (DDATHF), and 5
      deazafolic acid (efficient substrate for FPGS) were used as the basic structures
      in the present study, from which modifications were introduced in the
      pteridine/quinazoline ring, the C9-N10 bridge, the benzoyl ring, and the
      glutamate side chain. It was observed that RFC exhibited an efficient substrate
      affinity for all analogues except CB3717, 2-NH2-ZD1694, and glutamate side-chain
      modified FPGS inhibitors. Substitutions at the 2-position (e.g., 2-CH3) improved
      the RFC substrate affinity for methotrexate and aminopterin. Other good
      substrates included PT523 (N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl
      L-ornithine), 10-ethyl-10-deazaaminopterin, and DDATHF. With respect to mFBP,
      modifications at the N-3 and 4-oxo positions resulted in a substantial loss of
      binding affinity. Modifications at other sites of the molecule were well
      tolerated. Growth-inhibition studies identified a series of drugs that were
      preferentially transported via RFC (2,4-diamino structures) or mFBP (CB3717, 2-NH
      ZD1694, or 5,8-dideazaisofolic acid), whereas other drugs were efficiently
      transported via both transport pathways (e.g., DDATHF, ZD1694, BW1843U89, or
      LY231514). Given the fact that for an increasing number of normal and neoplastic
      cells and tissue, different expression levels of RFC and mFBP are being
      recognized, this folate antagonist structure-activity relationship can be of
      value for predicting drug sensitivity and resistance of tumor cells or drug
      related toxicity to normal cells and for the rational design and development of
      novel antifolates.

PMID- 7565627
TI  - ATP depletion and inactivation of an ATP-sensitive taurine channel by classic ion
      channel blockers.
AB  - Cell volume regulation in different cell types is mediated in part by plasma
      membrane channel(s) that allow taurine and other important intracellular organic
      osmolytes to efflux from the cell. Previous studies have demonstrated that
      intracellular ATP is required for activation of a volume-sensitive taurine
      permeable channel. The present study examined the relation between cellular ATP
      and ADP concentrations and swelling-induced [14C]taurine efflux and anion current
      (whole-cell patch-clamp) after exposure of isolated skate (Raja erinacea)
      hepatocytes to metabolic poisons and a series of ion channel blockers. When
      intracellular ATP content was lowered with gradually increasing concentrations of
      2,4-dinitrophenol, a sigmoidal relation between ATP content and volume-activated
      [14C]taurine efflux was observed. Taurine efflux was progressively inhibited over
      a relatively narrow range of intracellular ATP levels, indicating that
      physiologic alterations in cellular nucleotides may modulate the opening of the
      channel. Surprisingly, the inhibition of [14C]taurine efflux by a number of ion
      channel blockers [glibenclamide, 5-nitro-2-(3-phenylpropylamino)benzoate,
      diphenylamine-2-carboxylate, ketoconazole, gossypol, niflumic acid, and quinine]
      was related to a decrease in cellular ATP concentrations and ATP/ADP ratios,
      rather than to a direct interaction with the channel. In contrast, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid and pyridoxal-5-phosphate inhibited
      volume-activated anion channels but had no effect on cellular ATP levels. These
      findings suggest multiple sites for regulation of volume-sensitive osmolyte
      channels and indicate that some putative ion channel blockers may actually alter
      the activity of ATP-regulated transporters by depleting cellular ATP.

PMID- 7565629
TI  - The effect of temperature on the binding of sulfonamides to carbonic anhydrase
      isoenzymes I, II, and IV.
AB  - We report the effect of temperature on the equilibrium dissociation constants
      (Kl) for a series of six sulfonamides binding to three carbonic anhydrase (CA)
      isoenzymes (I, II, and IV). Kl values obtained at 0 degree, 15 degrees, and 23
      degrees under conditions of nearly constant and low substrate (CO2) concentration
      were used to calculate enthalpy and entropy changes associated with sulfonamide
      binding as well as to provide estimates of inhibitory potency of sulfonamides at
      37 degrees. We studies four classic sulfonamide (methazolamide, benzolamide,
      ethoxzolamide, and sulfanilamide) and the novel sulfonamides MK-507 (dorzolamide)
      and CF3SO2NH2. In all cases, the Kl was observed to increase with increasing
      temperature, which is consistent with a negative enthalpy of sulfonamide binding.
      The extrapolated increase in Kl over the 0-37 degrees temperature range varied
      from 4-fold for sulfanilamide binding to CA l to 14-fold for CF3SO2NH2 binding to
      CA IV, corresponding to binding enthalpy values of -7.2 to -11.7 kcal/mol. For CA
      II and I, entropy changes associated with sulfonamide binding were in general
      modest and ranged from -5.3 to +4.1 entropy units (eu) for five of the compounds
      tested. In contrast, ethoxzolamide binding was associated with a relatively large
      positive entropy change. Also, the variatione in k(on) and k(off) with
      temperature were studied for three sulfonamides binding to CA II. The association
      rate constants for methazolamide, benzolamide, and ethoxzolamide binding showed
      increases of 2-fold or less, whereas dissociation constants increased 3-9-fold
      over the range of 0-37 degrees. Thus, the temperature effect in increasing Kl is
      in large part due to a faster rate of sulfonamide dissociation. Apparent
      activation parameters at 23 degrees for k(on) were delta H++ = -2.35 to 3.8
      kcal/mol, delta G++ = 7.3 to 8.6 kcal/mol, and delta S++ = -16.2 to -32.7 entropy
      units. For k(off), the corresponding values were delta H++ = 5.6 to 14.5
      kcal/mol, delta G++ = 19.0 kcal/mol, and delta S++ = -14.8 to -45.7 entropy
      units.

PMID- 7565628
TI  - Mutation of carboxyl-terminal threonine residues in human m3 muscarinic
      acetylcholine receptor modulates the extent of sequestration and desensitization.
AB  - We previously reported that a mutant human m3 muscarinic acetylcholine receptor
      in which threonine residues at positions 550, 553, and 554 in the carboxyl
      terminus had been substituted with alanines showed a significant blockage of
      receptor down-regulation when expressed in Chinese hamster ovary-K1 cells.
      Because Chinese hamster ovary cells showed little receptor sequestration, in the
      present study we investigated further the effects of these mutations on
      sequestration and desensitization in human embryonic kidney (HEK) 293 cells. Wild
      type and mutant receptors were transiently transfected into HEK 293 cells. The
      level of m3 muscarinic acetylcholine receptor expression was approximately 300
      fmol/mg protein, and the transfection efficiency was approximately 30% for all
      receptors. Also, wild-type and mutant receptors induced similar 4-fold increases
      in phosphoinositide (PPI) hydrolysis and showed similar Ca2+ responses after
      carbachol (CCh) treatment. However, the sequestration of wild-type receptors,
      determined as the difference between the extent of binding of lipophilic and
      hydrophilic ligands, occurred in a time- and dose-dependent manner to a maximum
      of approximately 40% of total receptors. In contrast, sequestration was almost
      totally blocked in cells expressing Ala550,553 or Ala550,553,554 mutant
      receptors. To determine the functional significance of sequestration and
      investigate its relationship to receptor desensitization, cells were preincubated
      with CCh and then washed free of agonist and restimulated with CCh.
      Desensitization was manifest as a time- and concentration-dependent decrease in
      the ability of the second stimulation to increase PPl hydrolysis. One-hour
      pretreatment with 1 mM CCh decreased PPl hydrolysis by 24% for wild-type
      receptors but had no effect on the ability of the mutant receptors to respond to
      a second CCh challenge. Furthermore, inhibition of wild-type receptor
      sequestration by treatment with conconavalin A also blocked desensitization to a
      1-hr treatment with CCh. These results suggest that sequestration may be directly
      involved in m3 receptor desensitization at early times. More prolonged CCh
      treatment (3-9 hr) reduced the PPl hydrolysis response of the mutant and the wild
      type receptors, indicating that the mechanism of m3 receptor desensitization at
      later times involves multiple components.

PMID- 7565630
TI  - Determination of structural domains for G protein coupling and ligand binding in
      beta 3-adrenergic receptor.
AB  - The beta 3-adrenergic receptor (beta 3AR) is a member of the super-family of G
      protein-coupled receptors that are characterized by seven putative transmembrane
      helices connected by hydrophilic loops. The mechanism by which the activated beta
      ARs transmit the signals across the plasma membrane involves the stimulation of
      Gs, which in turn activates adenylyl cyclase, yielding the second messenger cAMP.
      In the present study, we created a series of mutant beta 3ARs to explore the
      structural basis for the subtype-specific binding of BRL 37344, a beta 3
      selective agonist, and for the coupling of the receptor to Gs. To study the
      mechanism of subtype-specific binding of BRL 37344, chimeric beta 2/beta 3ARs
      were constructed and expressed in Raji cells. Binding studies suggest that the
      transmembrane segment 5 region of the beta 3AR contains critical determinants for
      observed high affinity for BRL 37344. Previous studies of beta 2ARs have
      demonstrated a role for the third intracellular loop in activating Gs. To
      investigate the role of this region in the beta 3AR, we constructed mutant beta
      3ARs lacking a small segment of the amino- or carboxyl-terminal domain of the
      third intracellular loop. Expression of these mutant receptors in mouse L cells
      and Raji cells reveals that although both mutants are capable of binding the
      antagonist [125l]iodocyanopindolol, the agonist-stimulated cAMP production
      mediated by these mutant receptors is markedly attenuated or abolished. In
      addition, both mutant beta 3ARs exhibit an approximately 10-fold increase in
      affinity for agonist binding, whereas the affinity for antagonists is not
      affected. This increased agonist affinity is not altered by treatment with 100
      microM 5' quanylyl-imidodiphosphate, suggesting that these mutant receptors are
      uncoupled from G proteins. The results of the present study demonstrate that
      these regions of the third intracellular loop of beta 3AR are critical for
      coupling to G proteins and suggest a role for these regions in maintaining the
      resting state of the unliganded receptor.

PMID- 7565631
TI  - Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase (DT
      diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity
      and selectivity in human lung and breast cancer cell lines.
AB  - Bioreductive antitumor quinones require reductive metabolism to produce their
      cytotoxic effects. A series of these compounds was screened for relative rates of
      reduction by the two-electron reductase, NAD(P)H:quinone oxidoreductase (DTD).
      The antitumor quinones streptonigrin (SN), 2,5-diaziridinyl-3-phenyl-1,4
      benzoquinone (PDZQ), 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinine (MeDZQ), and
      [3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H-indole-4,7-dione)-propen ol] (EO9)
      were all excellent substrates for recombinant rat and human DTD. All four
      compounds were reduced by DTD at least 100 times faster than the clinically
      important bioreductive alkylating agent, mitomycin C (MC). Reduction of the
      antitumor quinones was generally 4-5 times more efficient by rat DTD than by
      human DTD. The exception was EO9, which, surprisingly, was reduced 23 times
      faster by rat DTD than by human DTD. The rate of reduction of each individual
      quinone was similar under either aerobic or anaerobic conditions, suggesting that
      DTD may be an important activating enzyme in the hypoxic fraction of solid
      tumors. The cytotoxicity of MeDZQ and MC was examined in a panel of human breast
      and lung cancer cell lines. The data showed good correlations between DTD
      activity and toxicity for both MeDZQ (r = 0.57, p = 0.054) and MC (r = 0.69, p =
      0.020), confirming biochemical data that both compounds are bioactivated by DTD.
      In addition, IC50 values were in general lower for MeDZQ than for MC in cell
      lines containing elevated DTD, a finding that was consistent with metabolic data
      that indicated that MeDZQ was a better substrate for DTD than MC. SR, defined as
      the ratio of the IC50 value for the H596 NSCLC cell line (undetectable DTD
      activity) to the IC50 value for the H460 NSCLC cell line (high DTD activity),
      were determined for all five antitumor quinones. SN was the most selective (SR =
      86) followed by EO9 (SR = 62), MeDZQ (SR = 17), and MC (SR = 11). Surprisingly,
      PDZQ, an excellent substrate for DTD, was toxic to both cell lines (SR = 1.8).
      These data suggest that antitumor quionones that are substrates for DTD may be
      selectively toxic to tumors with high DTD activity and may be useful in the
      treatment of those tumors.

PMID- 7565632
TI  - Effects of gamma-glutamyl hydrolase on folyl and antifolylpolyglutamates in
      cultured H35 hepatoma cells.
AB  - A subline of H35 hepatoma cells (H35D cells) that have been made resistant to
      5,10-dideazatetrahydrofolate exhibits an increase in gamma-glutamyl hydrolase
      (GH) activity. GH is a lysosomal enzyme in H35 and H35D cells on the basis of
      comparison of the distribution of enzyme activity with other known lysosomal
      enzymes. The hydrolysis rate of methotrexate polyglutamate with isolated, intact
      lysosomes is 4-5-fold greater in H35D cells than in H35 cells. GH activity in
      isolated lysosomes is in part dependent on the presence of a reducing agent such
      as mercaptoethanol. Permeabilization of lysosomal preparations from both cell
      types by Triton X-100 causes a 10-fold enhancement in GH activity. The result of
      the enhanced activity of GH in H35D cells is a marked reduction in
      antifolylpolyglutamate concentration, with the parent antifolate being the
      predominant intracellular species found under all conditions tested. Unlike
      antifolates, the total intracellular folate concentration is nearly identical in
      both cells under standard culture conditions up to 10 microns folic acid.
      However, the chain length of folylpolyglutamates consists of predominantly
      triglutamates and tetraglutamates in H35D cells with increased GH, whereas it
      consists of pentaglutamates and hexaglutamates in the parental cells. At 50 and
      100 microns folic acid, the folate accumulation in H35D cells is less than half
      that of H35 cells, and the predominant polyglutamate species in the H35D cells
      are the diglutamates through the tetraglutamates. The results demonstrate that
      the two H35 cell lines having equal folylpolyglutamate synthetase but that one
      with enhanced lysosomal GH activity exhibits a marked reduction in the amount and
      gamma-glutamyl chain length of folylpolyglutamates and antifolylpolyglutamates.

PMID- 7565633
TI  - The delta isomer of hexachlorocyclohexane induces rapid release of the myo
      inositol-1,4,5-trisphosphate-sensitive Ca2+ store and blocks capacitative Ca2+
      entry in rat basophilic leukemia cells.
AB  - Antigenic stimulation of rat basophilic leukemia cells releases Ca2+ from
      internal stores and increases membrane permeability to Ca2+. The delta isomer of
      hexachlorocyclohexane (delta-HCH) is structurally similar to myo-inositol-1,4,5
      trisphosphate (IP3) and is a potent releaser of stored Ca2+ from permeabilized
      cells. This release of Ca2+ is not mediated by a competitive interaction with the
      IP3 receptor on the Ca2+ release channel on the endoplasmic reticulum. In intact
      cells, delta-HCH and, to a lesser extent, lindane (gamma-hexachlorocyclohexane)
      transiently increase the intracellular Ca2+ concentration. The return to basal
      concentrations is mediated by the plasma membrane Ca2+ pumps and not by
      resequestration of Ca2+ into intracellular stores. Treatment of cells with delta
      HCH (25-100 microM), but not lindane, leads to a progressive inhibition of the
      antigen- and thapsigargin-stimulated Ca2+ signal. Caffeine, a modulator of the
      ryanodine receptor Ca2+ channel, attenuates the rise in intracellular Ca2+
      induced by delta-HCH, suggesting that ryanodine receptor-like Ca2+ channels may
      be present in RBL cells. At 25 microM delta-HCH, a concentration that does not
      inhibit the antigen-stimulated Ca2+ signal, the release of [3H]serotonin from
      antigen-stimulated cells is enhanced as is secretion of [3H]serotonin from cells
      pretreated with 25-100 microM lindane. The depletion of Ca2+ from intracellular
      stores by delta-HCH should evoke Ca2+ entry into the cells by a capacitative
      mechanism; however; divalent cation permeability across the plasma membrane (Mn2+
      influx) is not increased but rather is decreased by delta-HCH. An understanding
      of the mechanism of action of delta-HCH in releasing stored Ca2+ and blocking
      Ca2+ influx across the plasma membrane may provide insights into the regulation
      of capacitative Ca2+ entry in nonexcitable cells.

PMID- 7565634
TI  - Characterization of the interaction of the marine cyanobacterial natural product
      curacin A with the colchicine site of tubulin and initial structure-activity
      studies with analogues.
AB  - Curacin A, the major lipid constituent of a strain of the marine cyanobacterium
      Lyngbya majuscula obtained off the coast of Curacao, is a potent antimitotic
      agent that we have previously shown to inhibit microtubule assembly and
      colchicine binding to tubulin. In the present study, we report that curacin A
      probably binds in the colchicine site because it competitively inhibits the
      binding of [3H]colchicine to tubulin with an apparent Ki value of 0.6 microM and
      stimulates tubulin-dependent GTP hydrolysis, as do most other colchicine-site
      agents. The binding of curacin A to tubulin resembled the binding reactions of
      combretastatin A-4 and podophyllotoxin in contrast to that of colchicine in that
      it occurred as extensively on ice as at higher temperatures. However, once bound,
      the dissociation rate of curacin A from tubulin is very slow, more closely
      resembling that observed with colchicinoids (thiocolchicine was the drug
      examined) than the faster dissociation that occurs with combretastatin A-4 and
      podophyllotoxin. Because the molecular structure of curacin A is so different
      from that of previously described colchicine-site drugs (e.g., there is no
      aromatic moiety, and there are only two conjugated double bonds in its linear
      hydrocarbon chain), we have been examining the activities of natural isomers and
      synthetic derivatives. So far, only modest enhancement or reduction of activity
      has been observed with a variety of structural changes.

PMID- 7565635
TI  - Regulation of phosphoinositide-3-kinase by G protein beta gamma subunits in a rat
      osteosarcoma cell line.
AB  - Rat osteosarcoma 17/2.8 cells (Ros 17/2.8 cells) were labeled with [32P]PO4(2-),
      and their levels of inositol lipids were determined after stimulation with
      thrombin. Thrombin stimulated a pertussis toxin-sensitive rapid accumulation of
      phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3] with lesser increases
      in levels of phosphatidylinositol-3,4-bisphosphate [PtdIns(3,4)P2] and
      phosphatidylinositol-3-phosphate [PtdIns3P] that were slower in onset. Ros 17/2.8
      cell homogenates contained phosphatase activities that hydrolyzed PtdIns(3,4,5)P3
      to PtdIns(3,4)P2 and PtdIns3P. Phosphoinositide-3-kinase activity was determined
      in Ros 17/2.8 cell homogenates using exogenously provided PtdIns(4,5)P2.
      Guanosine-5'-3-O-(thio)triphosphate caused an approximately 3-fold increase in
      phosphoinositide-3-kinase activity in a manner that was blocked by high
      concentrations of guanosine-5'-2-O-(thio)diphosphate. Purified bovine brain G
      protein beta gamma subunits also increased phosphoinositide-3-kinase activity
      modestly in Ros 17/2.8 cell homogenates. Ros 17/2.8 cell homogenates contained
      phosphatase activities that sequentially dephosphorylated PtdIns(3,4,5)P3 to
      PtdIns(3,4)P2 and PtdIns3P. Two peaks of phosphoinositide-3-kinase activity were
      resolved by anion exchange chromatography of a Ros 17/2.8 cell cytosolic extract.
      The later elution of these was selectively activated by beta gamma subunits (16
      fold activation with 16 microM beta gamma subunits). Half-maximal effects of the
      beta gamma subunits were observed at a concentration of 0.6 microM, and
      activation was blocked by preincubation of the beta gamma subunits with an excess
      of recombinant Gi alpha 2. beta gamma Subunits did not activate the p85
      alpha/p110 beta form of phosphoinositide-3-kinase purified from sf9 cells after
      expression with the use of baculovirus vectors.

PMID- 7565637
TI  - Tumor necrosis factor-alpha and interleukin-1 alpha enhance glucose utilization
      by astrocytes: involvement of phospholipase A2.
AB  - Cytokines can be produced within the nervous system by various cell types,
      including astrocytes, which secrete them in response to pathological processes
      such as viral infections. Astrocytes are known to play an important role in the
      homeostasis of the nervous system, in particular, by contributing to the
      regulation of local energy metabolism. We report that tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) markedly stimulate glucose
      uptake and phosphorylation in primary cultures of neonatal murine astrocytes, as
      determined with [3H]-2-deoxyglucose ([3H]2DG). This effect is both concentration
      dependent, with observed EC50 values of 8 ng/ml for TNF-alpha and 30 pg/ml for IL
      1 alpha, and time dependent, with a maximal response observed 24 hr after
      cytokine application. The effects of TNF-alpha and IL-1 alpha on glucose uptake
      and phosphorylation appear to be mediated by the phospholipase A2 signal
      transduction pathway. Evidence in support of this includes (i) inhibition by
      mepacrine, a phospholipase A2 inhibitor, of [3H]2DG uptake evoked by TNF-alpha
      and IL-1 alpha, and (ii) stimulation of [3H]arachidonic acid release by TNF-alpha
      and IL-1 alpha. Protein kinase C activation does not appear to be involved as the
      specific protein kinase C inhibitor Ro 31-7549 does not abolish TNF-alpha- or IL
      1 alpha-induced increase in [3H]2DG uptake and phosphorylation. The additional
      glucose imported by astrocytes on exposure to TNF-alpha and IL-1 alpha is neither
      stored as glycogen nor released as glycolytically derived lactate, suggesting
      that it is processed through the tricarboxylic acid cycle or pentose phosphate
      pathway. These results demonstrate that TNF-alpha and IL-1 alpha can
      fundamentally perturb the energy metabolism of astrocytes, possibly impairing
      their ability to provide adequate energy substrates for neurons.

PMID- 7565636
TI  - Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels
      expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40
      5967).
AB  - Four different types of Ca2+ channel alpha 1 subunits, representing the major
      classes of voltage-gated Ca2+ channels, were individually coexpressed along with
      alpha 2/delta and beta 2b subunits in Xenopus oocytes. These subunits (and the
      encoded channel types and major tissues of origin) included alpha 1C (L-type,
      cardiac), alpha 1B (N-type, central nervous system), alpha 1A (P/Q-type, central
      nervous system), and alpha 1E (most likely R-type, central nervous system).
      Divalent cation currents through these channels (5 mM Ba2+) were evaluated with
      the two-microelectrode voltage-clamp technique. The expressed channels were
      compared with regard to their responses to a structurally novel,
      nondihydropyridine compound, mibefradil (Ro 40-5967). In the micromolar
      concentration range, this drug exerted clear inhibitory effects on each of the
      four channel types, reducing divalent cation current at all test potentials, with
      the non-L-type channels being more sensitive to inhibition than the L-type
      channels under fixed experimental conditions. For all channel types, mibefradil
      was a much more effective inhibitor at more depolarized holding potentials,
      suggesting tighter binding of the drug to the inactivated state than to the
      resting state. The difference in apparent affinities of resting and inactivated
      states of the channels, calculated based on a modulated receptor hypothesis, was
      30-70-fold. In addition, the time course of decay of Ca2+ channel current was
      accelerated in the presence of drug, consistent with open channel block. The
      effect of increasing stimulation frequency was tested for L-type channels and was
      found to greatly enhance the degree of inhibition by mibefradil, consistent with
      promotion of block by channel opening and inactivation. Allowing for state
      dependent interactions, the drug concentrations found to block L-, N-, Q-, and R
      type channels by 50% are at least 10-fold higher than half-blocking levels
      previously reported for T-type channels in vascular smooth muscle cells under
      similar experimental conditions. This may help explain the ability of the drug to
      spare working myocardium (strongly negative resting potential, dominance of L
      type channels in their resting state) while reducing contraction in blood vessels
      (presumably involving T-type channels or partially inactivated L-type channels).
      Thus, mibefradil is a new addition to the family of nonselective organic Ca2+
      channel inhibitors, as exemplified by bepridil and fluspirilene, and may prove
      useful as an experimental tool for studying diverse physiological events
      initiated by Ca2+ influx. It complements classes of drugs with relatively
      selective effects on L-type channels, as exemplified by nifedipine and diltiazem.

PMID- 7565638
TI  - A single amino acid change in the mouse peroxisome proliferator-activated
      receptor alpha alters transcriptional responses to peroxisome proliferators.
AB  - The mouse peroxisome proliferator-activated receptor alpha (mP-PAR alpha) can
      activate transcription from the CYP4A6 promoter in transient cotransfection
      experiments in the absence (intrinsic transactivation) or presence of added
      peroxisome proliferator. However, mPPAR alpha-G, in which glycine is substituted
      for Glu282, exhibits very low intrinsic transactivation and responds fully to
      added peroxisome proliferators. The two receptors, when expressed in COS-1 cells,
      are nuclear in localization, are expressed at similar levels, have similar
      stability, and bind DNA in vitro with similar efficiency. The phenotypic
      difference in intrinsic transactivation is not altered by overexpression of the
      human retinoid X receptor alpha. The mPPAR alpha-G mutant receptor displays a
      higher EC50 for pirinixic acid and for 5,8,11,14-eicosatetraynoic acid than the
      wild-type PPAR alpha. This difference in the apparent EC50 value is independent
      of the cell lines used and indicates that the Glu282 to glycine substitution
      alters the response of mPPAR alpha to peroxisome proliferators. The EC50 values
      obtained for each receptor with the CYP4A6 reporter construct are lower than
      those for a reporter derived from the acyl-CoA oxidase gene. In general, an
      inverse relation is evident between the apparent EC50 values and the extent of
      intrinsic transactivation observed. The difference in intrinsic transactivation
      may reflect the presence of an endogenous activator at a concentration that is
      not sufficient to activate the mPPAR alpha-G but that is sufficient to effect the
      intrinsic transactivation seen for the wild-type mPPAR alpha.

PMID- 7565639
TI  - Modulations in antioxidant enzymes in different tissues of marine bivalve Perna
      viridis during heavy metal exposure.
AB  - Lipid peroxidation induced by metals at sub-lethal levels, alter physiological
      and biochemical characteristics of biological systems. To counter the detrimental
      effects of the prooxidant activity of metals, a group of antioxidant enzyme
      systems function in the organisms. The present study was performed to investigate
      into the lipid peroxidation product formation due to the exposure to effects of
      the metals namely aluminium, lead and cadmium at sub-lethal concentrations and
      the biological response through protective antioxidant enzyme activity in the
      marine mussels, Perna viridis Lin.. This organism is a known bioindicator and
      bioconcentrator of metals in the environment. The results of the present study
      were: (a) accumulation of lead showed a definite linear increase during the
      period of exposure whereas aluminium and cadmium showed fluctuations. Mantle and
      gill tissues showed greater accumulation of metals when compared to digestive
      gland; (b) lead and aluminium induced lipid peroxidation was greater in tissues
      than the peroxidation induced by cadmium. Cadmium induced peroxidation was
      observed only after the day 7 of the exposure; (c) anti-oxidant enzymes activity
      levels were significantly higher in digestive gland and mantle than gills; (d)
      mantle was observed to significantly contribute to the organismal response to
      lipid peroxidation as indicated by high activity levels of anti-oxidant enzymes.

PMID- 7565640
TI  - Staphylococcal enterotoxin-B (SEB) alters [14C]-choline transport and
      phosphatidylcholine metabolism in cultured human kidney proximal tubular cells.
AB  - We studied the effects of SEB on [14C]-choline transport and metabolism of
      choline containing phospholipids in cultured human kidney proximal tubular (PT)
      cells. SEB increased the uptake of [14C]-choline in PT cells as a function of
      toxin concentration, incubation time, and pH. The maximum increase in uptake (3.5
      5-fold compared to control) was observed at a toxin concentration of 10
      micrograms/10(4) cells, at 4 h and at pH 7.4. Two toxins structurally related to
      SEB, Staphylococcal enterotoxin-A and toxic shock toxin (TST-1) failed to alter
      [14C]-choline uptake in PT cells, a finding which indicates that SEB-mediated
      alteration in choline uptake in PT cells has high specificity. We found that SEB
      markedly and significantly increased the incorporation of [14C]-choline into
      phosphatidylcholine, Iysophosphatidylcholine and sphingomyelin, but not into
      phosphatidylethanolamine. Maximum increase in the incorporation of [14C]-choline
      into phosphatidylcholine (3-fold compared to control) was observed at 4 h after
      incubation with toxin. In contrast, SEB did not alter the incorporation of [14C]
      choline in phosphatidylethanolamine. The cellular level of phosphatidylcholine
      was also increased (2-fold compared to control) in PT cells incubated with SEB.
      This was accompanied by a 3-to-4-fold increase in CTP; phosphocholine,
      cytidyltransferase activity. In sum, SEB specifically stimulates
      phosphatidylcholine synthesis in PT cells by increasing choline uptake or by
      activating CTP: phosphocholine, cytidyltransferase, or both. We believe this is
      the first-ever report indicating that a toxin can increase phosphatidylcholine
      synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565641
TI  - Characterization of the HeLa cell single-stranded DNA-dependent ATPase/DNA
      helicase II.
AB  - A single-stranded DNA-dependent ATPase activity, consisting of two subunits of 83
      kDa (p90) and 68 kDa (p70), was previously purified from HeLa cells (Vishwanatha,
      J.K. and Baril, E.F. (1990) Biochem 29, 8753-8759). Homology of the two subunits
      of single-stranded DNA-dependent ATPase with the human Ku protein (Cao et al.
      (1994) Biochem 33, 8548-8557) and identity of the Ku protein as the human DNA
      helicase II (Tuteja et al. (1994) EMBO J. 13, 4991-5001) have been reported
      recently. Using antisera raised against the subunits of the HDH II, we confirm
      that the Hela single-stranded DNA-dependent ATPase is the HDH II. Similar to the
      activity reported for Ku protein, ssDNA-dependent ATPase binds to double-stranded
      DNA and the DNA-protein complex detected by gel mobility shift assay consists of
      both the ATPase subunits. The p90 subunit is predominantly nuclear and is easily
      dissociated from chromatin. The p70 is distributed in cytosol and nucleus, and a
      fraction of the nuclear p70 protein is found to be associated with the nuclear
      matrix. Both the p90 and p70 subunits of the ATPase are present in G1 and S phase
      of the cell cycle and are rapidly degraded in the G2/M phase of the cell cycle.

PMID- 7565642
TI  - Phorbol ester and diacylglycerol activation of native protein kinase C species
      from various tissues.
AB  - The characteristics of PKC activation induced by a number of compounds were
      investigated using PKCs, partially-purified from sources with a naturally high
      abundance of certain Ca2+ dependent PKC isoforms. Native isoforms were used
      rather than PKC isoforms expressed from a baculovirus system to assess the effect
      of tissue specific factors on activity. However, some data using recombinant PKC
      alpha were included for comparison. The presence of specific PKC isoforms in
      different tissues was determined using Western blot analysis. Protein kinase C
      alpha, beta 1, delta, epsilon, and zeta/iota were all present in rat midbrain
      cytosolic extract, PKC alpha, beta 1, delta, and zeta/iota were present in spleen
      cytosol, and PKC alpha and zeta/iota were present in COS 7 cell cytosol. The
      predominance of alpha and beta activities in COS 7 and spleen extracts
      respectively was confirmed by enzymic assay. The PKC activity assay was
      configured such that the Ca2+ dependence of the PKC activity induced by different
      PKC activators could be determined. Phorbol 12,13-dibutyrate (PDBu) was virtually
      equipotent on the Ca(2+)-dependent PKC activity from midbrain and spleen and
      slightly less potent on that from COS 7 cells. In the absence of Ca2+, PDBu was
      considerably less potent overall (as, indeed, were the other PKC activators) and
      was less potent on COS 7 cell PKC than on those from midbrain or spleen. Mezerein
      was more potent than PDBu at inducing PKC activity in COS 7 cell extracts in
      either the absence or presence of Ca2+ whereas in the presence of Ca2+, mezerein
      was slightly less potent on midbrain and spleen than PDBu and equipotent in the
      absence of Ca2+. Maximum values for Ca(2+)-independent activation by mezerein
      indicated that this activator was particularly effective in recruiting Ca(2+)
      dependent PKC isoform activity in a Ca2+ free environment. The greater potency of
      mezerein on PKC alpha was confirmed using PKC alpha and beta further purified
      from rat spleen by hydroxylapatite (HAP) chromatography. The effects of both PDBu
      and mezerein were investigated using anterior pituitary tissue where a
      particularly high potency of mezerein in the absence of Ca2+ was noted. The
      diacylglycerol, 1,2-dioctanoyl-sn-glycerol (DOG), appeared to cause little or no
      activation of native Ca(2+)-dependent isoforms in Ca2+ free conditions unlike
      another longer chain diacylglycerol, 1,2-dioleoyl-sn-glycerol. Also DOG activated
      midbrain PKCs more potently than PKCs from spleen or COS 7 cells (or lung and
      pituitary tissue) in the presence of Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7565643
TI  - Interleukin-1 alpha (IL-1 alpha) production by alveolar macrophages in patients
      with acute lung diseases: the influence of zinc supplementation.
AB  - The relationship between zinc treatment and interleukin-1 alpha (IL-1 alpha)
      production by cultured alveolar macrophages (AM) in patients with pulmonary
      tuberculosis and bacterial pneumonia was investigated. AM (1 x 10(6) cells/ml)
      from 6 patients with pulmonary tuberculosis, 7 patients with bacterial pneumonia
      and 4 healthy volunteers were cultured with either two different concentrations
      of zinc chloride (Znl = 1 microgram/ml and Zn2 = 5 micrograms/ml) or cell culture
      media alone (control) for an initial period of 6 hours and then stimulated with 3
      different immunomodulator agents and reincubated for a further 24 h. IL-1 alpha
      in culture supernatants was measured by enzyme-linked immunosorbent assay
      (ELISA). In the absence of Znl or Zn2 Polyinosinic:Polycytidylic acid (Poly I:C 1
      microgram/ml), Lipopolysaccharide (LPS 100 ng/ml) and Tumour necrosis factor
      alpha (TNF-alpha 10 ng/ml) significantly increased the production of IL-1 alpha
      from AM in both patients and healthy subjects (p < 0.001) compared to control
      (media only). Zn1 and Zn2 significantly increased the production of IL-1 alpha (p
      < 0.001) in culture supernatants in the absence of either Poly I:C, LPS or TNF
      alpha in patients but not in healthy group. In contrast, the presence of LPS or
      TNF-alpha significantly reduced Zn1 or Zn2-stimulated release of IL-1 alpha from
      AM in patients and healthy subjects (p < 0.01). However, Poly I:C decreased only
      Zn1-stimulated release of IL-1 alpha. These results suggest that zinc can
      regulate the production of IL-1 alpha from AM in patients with pulmonary
      tuberculosis or bacterial pneumonia.

PMID- 7565644
TI  - The influence of lactate, pyruvate and glucose as exogenous substrates on free
      radical defense mechanisms in isolated rat hearts during ischaemia and
      reperfusion.
AB  - Previous studies have shown that exogenous lactate impairs mechanical function of
      reperfused ischaemic hearts, while pyruvate improves post-ischaemic recovery. The
      aim of this study was to investigate whether the diverging influence of exogenous
      lactate and pyruvate on functional recovery can be explained by an effect of the
      exogenous substrates on endogenous protecting mechanisms against oxygen-derived
      free radicals. Isolated working rat hearts were perfused by a Krebs-Henseleit
      bicarbonate buffer containing glucose (5 mM) as basal substrate and either
      lactate (5 mM) or pyruvate (5 mM) as cosubstrate. In hearts perfused with glucose
      as sole substrate the activity of glutathione reductase was decreased by 32%
      during 30 min of ischaemia (p < 0.10 versus control value), while the activity of
      superoxide dismutase and catalase was reduced by 27 and 35%, respectively, during
      5 min of reperfusion (p < 0.10 versus control value). The GSH level in the
      glucose group was reduced by 29% following 30 min of ischaemia and 35 min of
      reperfusion (p < 0.10). In lactate- and pyruvateperfused hearts there were no
      significant decreases of superoxide dismutase, catalase, glutathione peroxidase
      and glutathione reductase activity during 30 min of ischaemia, 5 min of
      reperfusion or 35 min of reperfusion. In pyruvate-perfused hearts the glutathione
      peroxidase activity was even increased by 43% during 30 min of ischaemia (p <
      0.05). Glutathione levels (reduced and oxidized) did not markedly change in the
      lactate and pyruvate groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565645
TI  - Detection of inner ear disease autoantibodies by immunoblotting.
AB  - To define further the character of autoantibodies against the inner ear in
      patients with inner ear disease, Autoantibodies in sera from 82 patients with
      inner ear disease were investigated by immunoblotting. The inner ear antigens
      were extracted from Hartley guinea pigs. Brain, kidney, lung, heart and liver
      extracts were also prepared. Antibodies against the inner ear were found in 32 of
      82 (39%) patients with inner ear disease. These sera reacted with the 30 and 58
      kDa bands of the inner ear extracts. The 30 kDa band was detected in sera from
      patients with various inner ear diseases, while the 58 kDa band reacted with sera
      of patients with idiopathic progressive sensorineural hearing loss. Only two of
      the 52 normal control sera had a very faint band at 30 kDa. Sixteen of 32
      positive sera were then used to probe Western blots of the brain, kidney, lung
      heart and liver extracts. The 58 kDa band was also found in the protein extracts
      of the brain, the lung, and the liver. On the other hand, preliminary
      purification of the 30 and 58 kDa proteins from the inner ear extracts were
      achieved by anion exchange chromatography. These results show that antibodies in
      sera from patients with inner ear disease reacted with at least two polypeptide
      bands (30 and 58 kDa) of guinea pig inner ear extracts, and the 58 kDa antigenic
      epitope was not cochlea specific.

PMID- 7565646
TI  - ATP-dependent activation of phospholipase C by antigen, NECA, Na3VO4, and GTP
      gamma-S in permeabilized RBL cell ghosts: differential augmentation by ATP,
      phosphoenolpyruvate and phosphocreatine.
AB  - Ghosts prepared from rat basophilic leukemia cells (RBL cell ghosts) and
      permeabilized with alpha-toxin from S. aureus are a simplified system for the
      study of Fc epsilon RI-mediated activation of phospholipase C (PLC). This
      activity is dependent upon ATP and magnesium, and is enhanced by the addition of
      another compound containing an energetic phosphate group, either
      phosphoenolpyruvate (PEP) or phosphocreatine (PCr). This effect appears to be
      specific for PEP and PCr in that other compounds with energetic phosphate bonds
      including fructose 1,6-bisphosphate and additional ATP are not effective. On the
      contrary, GTP-gamma-S, an activator of G proteins, activates PLC in the presence
      of ATP alone and this is not further enhanced by the addition of PEP. In addition
      to Fc epsilon RI and GTP-gamma-S, two other stimuli lead to enhanced activity of
      PLC in permeabilized RBL cell ghosts: 1) an inhibitor of tyrosine phosphatases
      (Na3VO4) and 2) an analog of adenosine (NECA). Data presented here extend
      previous results to show that activation of PLC by GTP-gamma-S is not enhanced
      either by the addition of PCr or by the addition of a more MgATP. Further new
      findings include the observations that activation of PLC by Na3VO4 is augmented
      by PEP and PCr in a fashion similar to that observed for Fc epsilon RI-mediated
      activation of PLC and that activation of PLC by NECA shows even more marked
      dependency on PEP than does activation by Fc epsilon RI or Na3VO4.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7565647
TI  - GTP gamma S restores nucleophosmin (NPM) localization to nucleoli of GTP-depleted
      HeLa cells.
AB  - Previous studies showed that localization of nucleophosmin/B23 (NPM) to nucleoli
      requires adequate cellular GTP levels (Finch et al., J Biol Chem 268, 5823-5827,
      1993). In order to study whether hydrolysis of GTP plays a role in NPM
      localization, we introduced a nonhydrolyzable GTP analog into HeLa cells. Cells
      were first depleted of GTP with the IMP dehydrogenase inhibitor, mycophenolic
      acid (MA), to induce translocation of NPM from the nucleoli to the nucleoplasm.
      Non-hydrolyzable GTP analogs were then introduced into cells by electroporation.
      We found that introduction of the non-hydrolyzable analog, GTP gamma S, was
      effective in restoring NPM localization to nucleoli. Cells incubated in medium
      containing G-nucleotides without electroporation showed no effect. To reduce the
      possibility that cells use guanine from degraded nucleotide to supplement GTP
      pools via salvage pathways, experiments were also performed in the presence of (6
      mercaptopurine) 6MP, a competitive inhibitor of the salvage enzyme, HGPRT
      (hypoxanthine guanine phosphoribosyl transferase), in addition to MA. Under these
      conditions, introduction of GTP gamma S still effectively restored the
      localization of NPM into nucleoli. This study demonstrates that electroporation
      can be used effectively to introduce nucleotides into cultured cells without
      excessive loss of viability. Our results also indicate that the GTP dependent
      localization of NPM to the nucleoli may not require GTP hydrolysis.

PMID- 7565648
TI  - Enhancement of nuclear Ca(2+)-ATPase activity in regenerating rat liver:
      involvement of nuclear DNA increase.
AB  - The alteration of calcium content, Ca(2+)-ATPase activity, DNA content and DNA
      fragmentation in the nuclei of regenerating rat liver was investigated. Liver was
      surgically removed about 70% of that of sham-operated rats. The reduced liver
      weight by partial hepatectomy was completely restored at 3 days after the
      surgery. Regenerating liver significantly increased Ca(2+)-ATPase activity and
      DNA content in the nuclei between 1 and 5 days after hepatectomy. The nuclear
      calcium content was clearly increased from 2 days after hepatectomy. The increase
      of Ca(2+)-ATPase activity in regenerating liver was clearly inhibited by the
      presence of trifluoperazine (10 microM), staurosporine (2.5 microM) and dibucaine
      (10 microM), which are inhibitors of calmodulin and protein kinase, in the enzyme
      reaction mixture. However, the nuclear enzyme activity in normal rat liver was
      not significantly altered by these inhibitors. Meanwhile, the increase of nuclear
      DNA content in regenerating liver was completely blocked by the administration of
      trifluoperazine (2.5 mg/100 g body weight), suggesting an involvement of
      calmodulin. Now, the nuclear DNA fragmentation was significantly decreased in
      regenerating liver, suggesting that this decrease is partly contributed to the
      increase in nuclear DNA content. The present study clearly demonstrates that
      regenerating liver enhances nuclear Ca(2+)-ATPase activity and induces a
      corresponding elevation of nuclear calcium content. This Ca(2+)-signaling system
      may be involved in the regulation of nuclear DNA functions in regenerating rat
      liver.

PMID- 7565649
TI  - Role of hydroxyl radical in the stimulation of arachidonic acid release caused by
      H2O2 in pulmonary smooth muscle cells: protective effect of anion channel
      blocker.
AB  - We sought to investigate role of hydroxyl radical (OH.) in H2O2 caused
      stimulation of arachidonic acid (AA) release from rabbit pulmonary arterial
      smooth muscle cells, and to ascertain protective effect of the anion channel
      blocker DIDS in this phenomenon. Exposure of the smooth muscle cells to the
      oxidant H2O2 (1mM) stimulates iron release and enhances AA liberation from the
      cells. Pretreatment of the cells with either deferoxamine (DFO) or dimethyl
      thiourea (DMTU) markedly reduces AA release and prevents OH. production without
      causing any appreciable reduction of iron release caused by H2O2. Simultaneous
      treatment of either DFO or DMTU with H2O2 significantly reduces AA release, and
      also prevents OH. production without causing any significant reduction of iron
      release. In contrast, addition of either DFO or DMTU even 2 min after exposure of
      the cells to H2O2 does not cause any significant reduction of AA release, OH.
      production and iron release. Pretreatment of the cells with DIDS markedly reduces
      AA release caused by H2O2 without producing any discernible reduction of iron
      release, and OH. production.

PMID- 7565650
TI  - Lipid peroxidation of erythrocytes during anemia of the hamsters infected with
      Leishmania donovani.
AB  - Visceral leishmaniasis has been found to be associated with severe anemia and
      premature lysis of erythrocytes. Peroxidative damage of red cells has been noted
      in several hemolytic anemias. Present study shows enhanced formation of
      methemoglobin in hamsters infected with Leishmania donovani. Increased formation
      of malonyldialdehyde and diene conjugate has been noted in the erythrocytes of
      the infected animals with the progress of anemia. Results showed decreased
      activities of protective enzymes like superoxide dismutase, catalase and
      glutathione reductase against peroxidative attack. An increase in the membrane
      cholesterol/phospholipid ratio and a decrease in membrane fluidity of
      erythrocytes were observed under the diseased condition. Densitometric scan after
      SDS-PAGE of red cell membrane of the infected animals revealed significant
      degradation of band 3 and band 4.1 proteins. The results suggest that alteration
      in the membrane may lead to reduced life span of the red cells in experimental
      visceral leishmaniasis.

PMID- 7565651
TI  - Single-stranded DNA binding protein encoded by the filamentous bacteriophage M13:
      structural and functional characteristics.
AB  - The single-stranded DNA binding protein, or gene V protein (gVp), encoded by gene
      V of the filamentous bacteriophage M13 is a multifunctional protein that not only
      regulates viral DNA replication but also gene expression at the level of mRNA
      translation. It furthermore is implicated as a scaffolding and/or chaperone
      protein during the phage assembly process at the hostcell membrane. The protein
      is 87 amino acids long and its biological functional entity is a homodimer. In
      this manuscript a short description of the life cycle of filamentous phages is
      presented and our current knowledge of the major functional and structural
      properties and characteristics of gene V protein are reviewed. In addition models
      of the superhelical complexes gVp forms with ssDNA are described and their
      (possible) biological meaning in the infection process are discussed. Finally it
      is described that the 'DNA binding loop' of gVp is a recurring motif in many
      ssDNA binding proteins and that the fold of gVp is shared by a large family of
      evolutionarily conserved gene regulatory proteins.

PMID- 7565652
TI  - Effect of CPT on the DNA cleavage/religation reaction mediated by calf thymus
      Topoisomerase I: evidence of an inhibition of DNA religation. Inhibition of
      Topoisomerase I-mediated DNA religation by CPT.
AB  - The uncoupling of the calf thymus Topoisomerase I-mediated forward DNA cleavage
      reaction from the religation event by a rapid shift of cleavage temperature
      either from 37 degrees C to 0 degrees C or from 37 degrees C to 56 degrees C has
      been studied and utilized to elucidate the molecular mechanism by which
      camptothecin, a clinically relevant antineoplastic agent, influences the half
      reactions of the enzyme. Results of heating and cooling religation-inducing
      treatments have been compared: both temperature extremes reduce the amount of
      protein-linked DNA breaks to background levels, thereby affecting cleavage
      reversal. Camptothecin is found to stabilize the enzyme-DNA intermediate, by
      inhibition of the Topoisomerase I-mediated rejoining of cleaved DNA, even when
      the drug is added after formation of the complex. We conclude that: 1. Heating
      and cooling treatments show a pronounced effect on the DNA cleavage-religation
      equilibrium. The efficacy of cold is more pronounced than that of heat. 2.
      Reversal of the enzyme-DNA intermediate favors the DNA resealing versus the
      closed relaxed form. 3. Camptothecin affects the heat or cold induced religation:
      in fact in both cases the drug delays the religation step.

PMID- 7565653
TI  - Isolation and characterization of a multienzyme complex containing DNA
      replicative enzymes from mitochondria of S. cerevisiae. Multienzyme complex from
      yeast mitochondria.
AB  - A 40 S multienzyme complex containing mtDNA polymerase was isolated from
      mitochondria of S. cerevisiae by density gradient centrifugation and by gel
      filtration chromatography. Besides DNA polymerase, RNA polymerase, primase, 3'-
      >5' exonuclease and an ATPase activities were found to be associated with it. The
      presence of some of these enzymes were confirmed by Western blot. This high
      molecular weight multienzyme complex containing DNA has most of the attributes of
      a putative replisome.

PMID- 7565655
TI  - Determination of base specificity of multiple ribonucleases from crude samples.
AB  - Ribonucleases are widely found on the tissues of living organisms, but the
      functions of individual ribonucleases are not clear. To facilitate
      characterization of individual ribonucleases, I have developed a rapid method to
      separate and identify each ribonuclease from a crude sample by gel
      electrophoresis instead of by time-consuming purification steps. The
      ribonucleases in a crude sample are first separated by RNA-cast SDS
      polyacrylamide gel electrophoresis and then eluted from the gel after ethidium
      bromide staining. To determine the base specificity of each ribonuclease, a 5'
      labelled oligonucleotide with known sequence is added to the enzyme eluate and
      the digested products are analyzed by denaturing gel electrophoresis. The base
      specificity of bovine pancreatic ribonuclease (RNase A), bullfrog oocyte-specific
      ribonuclease (RC-RNase), human serum ribonucleases and sweet potato leaf
      ribonucleases were determined by this method. Other properties of individual
      ribonucleases, e.g. substrate preference, may also be determined from crude
      samples by this method without further purification steps.

PMID- 7565654
TI  - SV40 large T antigen-induced inhibition of terminal differentiation of primary
      skeletal muscle cells is associated with a block in the expression of MyoD and
      myogenin.
AB  - Transformation of hamster primary myoblasts with the SV40 large T antigen leads
      to inhibition of terminal differentiation. This process is associated with a
      block in the transcription of the muscle-specific determinator genes MyoD and
      myogenin. The effect of SV40 large T antigen on the terminal differentiation is
      dominant and cannot be bypassed by re-expression of retrovirally encoded MyoD.
      The intermediate filament protein desmin is normally up-regulated when myoblasts
      differentiate into myotubes. Surprisingly, desmin is expressed at relatively high
      levels in transformed hamster muscle cells grown under proliferative conditions.
      So desmin expression can be independent of the onset of differentiation. This is
      in accordance with the expression of the protein in fibroblasts, infected with a
      MyoD-encoding retrovirus and grown under proliferative conditions, when no other
      muscle-specific proteins are present.

PMID- 7565656
TI  - A novel human type I hair keratin gene: evidence for two keratin hHa3 isoforms.
AB  - We present the nucleotide and amino acid sequence for a novel human type I hair
      keratin, which could be identified through its high sequence homology and strict
      carboxyterminal length identity as a human ortholog of the murine hair keratin
      mHa3. Our hHa3 sequence differs, however, from that of a previously described
      hHa3 hair keratin (published only as an amino acid sequence; [13]) in 24 amino
      acid position, 8 of which occur in the middle of the carboxyterminal domain. PCR
      of genomic DNA from 25 normal human subjects using a primer pair derived from
      sequence segments located in the 3'-region of our hHa3 clone that encode
      conserved amino acid sequences in both keratins, resulted in the amplification of
      two distinct products of 0.38 kbp and 1.0 kbp. DNA sequence analysis of the
      cloned PCR products allowed identification of the 0.38 kb sequence as that
      originating from Yu et al. [13] and the 1.0 kb sequence as that being derived
      from our data. The difference in fragment length was due to unique intron 6
      sequences, indicating that these two keratin species are encoded by genes of
      their own. Moreover, extensive Southern blot analyses with DNA from 25 unrelated
      individuals of different races using a 3'-noncoding sequence from our keratin and
      the intron 6 sequence of the keratin of Yu et al. [13], as hybridization probes
      showed that both keratin genes are present as single copy sequences occurring
      ubiquitously and without gross alterations in the human genome. Collectively,
      these data demonstrate that the human type I hair keratin described in this paper
      represents an isoform of the previously described hHa3 keratin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7565657
TI  - In vitro nucleo-cytoplasmic transport.

PMID- 7565658
TI  - Structural features of archaebacterial and eukaryotic proteasomes.
AB  - The 26S proteasome is the central protease of the ubiquitin-dependent pathway of
      protein degradation. The molecule has a molecular mass of approximately 2000 kD
      and has a highly conserved structure in eukaryotes. The 26S proteasome is formed
      by a barrel-shaped 20S core complex and two polar 19S complexes. The 20S complex
      has C2 symmetry and is formed by four seven-membered rings of which the outer
      rings (alpha-type subunits) are rotated by 25.7 degrees relative to the inner
      rings while the inner rings (beta-type subunits) are in register. From a
      comparison of the activity and regulation of the 26S and 20S particles it can be
      deduced that the 20S particle contains the protease activity while the 19S
      complex contains isopeptidase, ATPase and protein unfolding activities. In this
      article we describe the structures of various proteasome complexes as determined
      by electron microscopy and discuss structural implications of their subunit
      sequences.

PMID- 7565659
TI  - Molecular biology of proteasomes.
AB  - Eukaryotic proteasomes are unusually large proteins with a heterogeneous subunit
      composition and have been classified into two isoforms with apparently distinct
      sedimentation coefficients of 20S and 26S. The 20S proteasome is composed of a
      set of small subunits with molecular masses of 21-32 kDa. The 26S proteasome is a
      multi-molecular assembly, consisting of a central 20S proteasome and two terminal
      subsets of multiple subunits of 28-112 kDa attached to the central part in
      opposite orientations. The primary structures of all the subunits of mammalian
      and yeast 20S proteasomes have been deduced from the nucleotide sequences of
      cDNAs or genes isolated by recombinant DNA techniques. These genes constitute a
      unique multi-gene family encoding homologous polypeptides that have been
      conserved during evolution. In contrast, little is yet known about the terminal
      structures of the 26S proteasome, but the cDNA clonings of those of humans are
      currently in progress. In this review, I summarize available information of the
      structural features on eukaryotic 20S and 26S proteasomes which has been
      clarified by molecular-biological methods.

PMID- 7565660
TI  - Subunits of the regulatory complex of the 26S protease.

PMID- 7565662
TI  - Catalytic components of proteasomes and the regulation of proteinase activity.
AB  - The proteasome (multicatalytic proteinase complex) is a large multimeric complex
      which is found in the nucleus and cytoplasm of eukaryotic cells. It plays a major
      role in both ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways
      of protein degradation. Proteasome subunits are encoded by members of the same
      gene family and can be divided into two groups based on their similarity to the
      alpha and beta subunits of the simpler proteasome isolated from Thermoplasma
      acidophilum. Proteasomes have a cylindrical structure composed of four rings of
      seven subunits. The 26S form of the proteasome, which is responsible for
      ubiquitin-dependent proteolysis, contains additional regulatory complexes.
      Eukaryotic proteasomes have multiple catalytic activities which are catalysed at
      distinct sites. Since proteasomes are unrelated to other known proteases, there
      are no clues as to which are the catalytic components from sequence alignments.
      It has been assumed from studies with yeast mutants that beta-type subunits play
      a catalytic role. Using a radiolabelled peptidyl chloromethane inhibitor of rat
      liver proteasomes we have directly identified RC7 as a catalytic component.
      Interestingly, mutants in Pre1, the yeast homologue of RC7, have already been
      reported to have defective chymotrypsin-like activity. These results taken
      together confirm a direct catalytic role for these beta-type subunits. Proteasome
      activities are sensitive to conformational changes and there are several ways in
      which proteasome function may be modulated in vivo.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7565661
TI  - Proteasomes of the yeast S. cerevisiae: genes, structure and functions.
AB  - Proteasomes are large multicatalytic protease complexes which fulfil central
      functions in major intracellular proteolytic pathways of the eukaryotic cell. 20S
      proteasomes are 700 kDa cylindrically shaped particles, found in the cytoplasm
      and the nucleus of all eukaryotes. They are composed of a pool of 14 different
      subunits (MW 22-25 kDa) arranged in a stack of 4 rings with 7-fold symmetry. In
      the yeast Saccharomyces cerevisiae a complete set of 14 genes coding for 20S
      proteasome subunits have been cloned and sequenced. 26S proteasomes are even
      larger proteinase complexes (about 1700 kDa) which degrade ubiquitinylated
      proteins in an ATP-dependent fashion in vitro. The 26S proteasome is build up
      from the 20S proteasome as core particle and two additional 19S complexes at both
      ends of the 20S cylinder. Recently existence of a 26S proteasome in yeast has
      been demonstrated. Several 26S proteasome specific genes have been cloned and
      sequenced. They share similarity with a novel defined family of ATPases. 20S and
      26S proteasomes are essential for functioning of the eukaryotic cell. Chromosomal
      deletion of 20S and 26S proteasomal genes in the yeast S. cerevisiae caused
      lethality of the cell. The in vivo functions of proteasomes in major proteolytic
      pathways have been demonstrated by the use of 20S and 26S proteasomal mutants.
      Proteasomes are needed for stress dependent and ubiquitin mediated proteolysis.
      They are involved in the degradation of short-lived and regulatory proteins.
      Proteasomes are important for cell differentiation and adaptation to
      environmental changes. Proteasomes have also been shown to function in the
      control of the cell cycle.

PMID- 7565663
TI  - Relationships between proteasomes and RNA.
AB  - The 20S proteasome (prosome) is a highly organized multi-protein complex with
      approximate molecular weight of about 700 kDa. Whilst the role of the proteasome
      in the processing and turnover of cellular proteins is becoming clearer, its
      relationship with RNA remains obscure. Over the last decade the possibility of
      association of proteasomes with specific RNAs or mRNPs have been particularly
      controversial. Proteasomes were reported to inhibit translation of viral mRNAs
      and to be tightly associated with RNase activity. It is possible that proteasomes
      are also involved in cellular RNA breakdown and RNA processing like prokaryotic
      RNase E.

PMID- 7565664
TI  - Roles of proteasomes in cell growth.
AB  - Proteasomes are large, unique protein complexes catalyzing energy- and ubiquitin
      dependent proteolysis. Recent studies have revealed that these complexes are
      involved in two important cellular functions. One is to make antigen fragments
      for major histo-compatibility complex (MHC) class I-restricted antigen
      presentation and the other is to regulate the cell cycle by proteolysis. Here we
      review only the latter function of proteasomes. Proteasomes are widely
      distributed in eukaryotic cells, but their levels have been shown to be
      particularly high in various immature cells, such as cancerous, fetal and
      lymphoblastic cells, and agents including cell differentiation were found to
      suppress their expression. These conditions also regulate the expression of
      ubiquitin genes in a similar way, suggesting that proteasomes act ubiquitin
      dependently in their 26S form in immature cells. High levels of proteasomes were
      found immunochemically in the nuclei of rapidly growing cells, indicating that
      proteasomes are important for eukaryotic cell growth. Indeed, gene disruptions of
      most subunits of proteasomes in yeast resulted in total suppression of cell
      growth and cell death. Short-lived regulatory factors of the cell cycle, such as
      Fos, p53, Mos, and cyclins are degraded by the proteasome-ubiquitin pathway under
      phosphorylated or dephosphorylated conditions. Ornithine decarboxylase, which is
      also a short-lived enzyme and is involved in the early phase of cell growth, is
      quickly degraded by proteasomes with antizyme, but without ubiquitination.
      Recently, we found that one of the regulatory factors of 26S proteasomes, p31, is
      a homologue of Nin1p, whose mutation caused inhibition of the cell cycle in
      yeast. These results indicate that proteasomes play important roles in regulation
      of the cell cycle in eukaryotes.

PMID- 7565665
TI  - Proteasome and class I antigen processing and presentation.
AB  - The recent discovery of two proteasome homologous genes, LMP2 and LMP7, in the
      class II region of the human MHC, has implicated this multi-subunit protease in
      an early step of the immune response; the degradation of intracellular and viral
      proteins. Short peptides produced by the proteasome are transported into the ER
      by the product of another set of MHC class II genes, TAP1 and TAP2, where they
      bind and stabilise HLA class I molecules. Antigenic peptides displayed at the
      cell surface by HLA class I molecules mark cells for destruction by cytotoxic T
      lymphocytes. The role of the proteasome in antigen processing was questioned when
      mutant cells, which lack the LMP genes, were able to process and present antigens
      normally. The discovery that two proteasome beta-subunits, delta and MB1, highly
      homologous to LMP2 and LMP7 and expressed in reciprocal manner, is now consistent
      with a role for the proteasome in antigen processing. The incorporation of
      different beta-subunits into the proteasome may be a mechanism to modulate
      catalytic activity of the proteasome complex, allowing production of peptides
      that are more suitable to enter into the ER by the TAP transporters and to bind
      HLA class I molecules. But, in the absence of the LMPs, the other subunits permit
      processing of most antigens reasonably efficiently.

PMID- 7565668
TI  - Proteolytic activity of proteasome on myofibrillar structures.
AB  - The physiologic function of proteasome remains unclear. Evidence suggests a role
      in degradation of ubiquitin-protein conjugates, MHC antigen presentation, and
      some specificity of substrate within certain cell types. To explore further the
      properties of proteasome we have examined its effect on a well defined structure,
      the myofibril. We find that despite its large size (20S) proteasome is able to
      degrade myofibrils and intact, permeabilized muscle fibrils. The proteins
      degraded showed some specificity because actin, myosin and desmin were degraded
      faster than alpha-actinin, troponin T and tropomyosin. Changes in ultrastructure
      were slow and included a general loss of structure with Z and I bands effected
      before the M band and costameres.

PMID- 7565667
TI  - Multicatalytic proteinase in fish muscle.
AB  - A partially active and a latent form of multicatalytic protease (MCP) were
      isolated from fish skeletal muscle. Both forms were inactive against protein
      substrates, but their activity against peptide substrates differed in one order
      of magnitude. The chymotrypsin-like activity of the partially active form was
      moderately stimulated by fatty acids and SDS, whereas its trypsin-like activity
      was inhibited by the same reagents. In contrast, both activities of the latent
      form were strongly stimulated by SDS. The chymotrypsin-like activity of the
      latent form was also stimulated by heating or high urea concentrations, whereas
      its trypsin-like activity did not change or was inhibited respectively by these
      treatments. These activation effects were irreversible. Pre-treatment of the
      latent form with SDS or urea in the absence of substrate led to its irreversible
      inactivation, whereas activation by pre-heating occurred in the presence or
      absence of substrate. These results suggest that MCP can exist in several active
      states with distinct properties. Studies on the distribution of MCP in fish
      tissues showed a much higher level of the enzyme in gonads than in any other
      tissue, suggesting a role of MCP in development.

PMID- 7565666
TI  - The 20S/26S proteasomal pathway of protein degradation in muscle tissue.
AB  - Similar to all other eukaryotic cells and tissues muscle tissue contains the
      proteolytic system of 20S/26S proteasomes with the 20S proteasome existing
      predominantly in a latent state. Unlike with the mammalian enzyme in vitro
      transition from the latent to the activated state of the 20S proteasomes isolated
      from muscle of several fish species and from lobster can be achieved by heat
      shock. It is very likely that the activated state of the 20S proteasome
      corresponds to the physiologically active form of the enzyme since only that one
      is able to attack sarcoplasmic and myofibrillar proteins to any significant
      extent. As perfusion of rat hindquarters with presumptive low molecular mass
      activators like free fatty acids does not result in an activation of the muscle
      proteasome other--possibly protein activators--may serve this purpose in vivo.
      The 26S proteasome complex may be regarded as such a proteasome/activator
      complex. The 26S proteasome complex has the ability to degrade protein (
      ubiquitin-conjugates) by an ATP-consuming reaction. Since increased amounts of
      ubiquitinated proteins as well as an enhanced activity of the ATP (-ubiquitin)
      dependent proteolytic system have been measured in rat muscle tissue during
      various catabolic conditions, it is not unlikely that this pathway is responsible
      for catalysis of muscle protein breakdown.

PMID- 7565669
TI  - Ras p21Val inhibits myogenesis without altering the DNA binding or
      transcriptional activities of the myogenic basic helix-loop-helix factors.
AB  - MRF4, MyoD, myogenin, and Myf-5 are muscle-specific basic helix-loop-helix
      transcription factors that share the ability to activate the expression of
      skeletal muscle genes such as those encoding alpha-actin, myosin heavy chain, and
      the acetylcholine receptor subunits. The muscle regulatory factors (MRFs) also
      exhibit the unique capacity to initiate the myogenic program when ectopically
      expressed in a variety of nonmuscle cell types, most notably C3H10T1/2
      fibroblasts (10T1/2 cells). The commitment of myoblasts to terminal
      differentiation, although positively regulated by the MRFs, also is controlled
      negatively by a variety of agents, including several growth factors and
      oncoproteins such as fibroblast growth factor (FGF-2), transforming growth factor
      beta 1 (TGF-beta 1), and Ras p21Val. The molecular mechanisms by which these
      varied agents alter myogenic terminal differentiation events remain unclear. In
      an effort to establish whether Ras p21Val represses MRF activity by directly
      targeting the MRF proteins, we examined the DNA binding and transcription
      activation potentials of MRF4 and MyoD when expressed in 10T1/2 cells or in
      10T1/2 cells expressing Ras p21Val. Our results demonstrate that Ras p21Val
      inhibits terminal differentiation events by targeting the basic domain of the
      MRFs, and yet the mechanism underlying this inhibition does not involve altering
      the DNA binding or the inherent transcriptional activity of these regulatory
      factors. In contrast, FGF-2 and TGF-beta 1 block terminal differentiation by
      repressing the transcriptional activity of the MRFs. We conclude that the Ras
      p21Val block in differentiation operates via an intracellular signaling pathway
      that is distinct from the FGF-2 and TGF-beta 1 pathways.

PMID- 7565670
TI  - A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and
      regulates MEK function.
AB  - Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both
      from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the
      JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in
      MEKs that are regulated by Raf family enzymes but is missing from MEKs and SEKs
      activated independently of Raf, we sought to investigate the role of this
      sequence in MEK1 and MEK2 regulation and function. Deletion of the PR sequence
      from MEK1 blocked the ability of MEK1 to associate with members of the Raf family
      and markedly attenuated activation of the protein in vivo following growth factor
      stimulation. In addition, this sequence was necessary for efficient activation of
      MEK1 in vitro by B-Raf but dispensable for activation by a novel MEK1 activator
      which we have previously detected in fractionated fibroblast extracts.
      Furthermore, we found that a phosphorylation site within the PR sequence of MEK1
      was required for sustained MEK1 activity in response to serum stimulation of
      quiescent fibroblasts. Consistent with this observation, we observed that MEK2,
      which lacks a phosphorylation site at the corresponding position, was activated
      only transiently following serum stimulation. Finally, we found that deletion of
      the PR sequence from a constitutively activated MEK1 mutant rendered the protein
      nontransforming in Rat1 fibroblasts. These observations indicate a critical role
      for the PR sequence in directing specific protein-protein interactions important
      for the activation, inactivation, and downstream functioning of the MEKs.

PMID- 7565671
TI  - New retinoid X receptor subtypes in zebra fish (Danio rerio) differentially
      modulate transcription and do not bind 9-cis retinoic acid.
AB  - Retinoid X receptors (RXRs), along with retinoic acid (RA) receptors (RARs),
      mediate the effects of RA on gene expression. Three subtypes of RXRs (alpha,
      beta, and gamma) which bind to and are activated by the 9-cis stereoisomer of RA
      have been characterized. They activate gene transcription by binding to specific
      sites on DNA as homodimers or as heterodimers with RARs and other related nuclear
      receptors, including the vitamin D receptor, thyroid hormone receptors (TRs), and
      peroxisome proliferator-activated receptors. Two additional RXR subtypes (delta
      and epsilon) isolated from zebra fish cDNA libraries are described here; although
      both subtypes form DNA-binding heterodimers with RARs and TR, neither binds 9-cis
      RA, and both are transcriptionally inactive on RXR response elements. In
      cotransfection studies with TR, the delta subtype was found to function in a
      dominant negative manner, while the epsilon subtype had a slight stimulatory
      effect on thyroid hormone (T3)-dependent transcriptional activity. The discovery
      of these two novel receptors in zebra fish expands the functional repertoire of
      RXRs to include ligand-independent and dominant negative modulation of type II
      receptor function.

PMID- 7565672
TI  - Translational regulation in response to changes in amino acid availability in
      Neurospora crassa.
AB  - We examined the regulation of Neurospora crassa arg-2 and cpc-1 in response to
      amino acid availability.arg-2 encodes the small subunit of arginine-specific
      carbamoyl phosphate synthetase; it is subject to unique negative regulation by
      Arg and is positively regulated in response to limitation for many different
      amino acids through a mechanism known as cross-pathway control. cpc-1 specifies a
      transcriptional activator important for crosspathway control. Expression of these
      genes was compared with that of the cytochrome oxidase subunit V gene, cox-5.
      Analyses of mRNA levels, polypeptide pulse-labeling results, and the distribution
      of mRNA in polysomes indicated that Arg-specific negative regulation of arg-2
      affected the levels of both arg-2 mRNA and arg-2 mRNA translation. Negative
      translational effects on arg-2 and positive translational effects on cpc-1 were
      apparent soon after cells were provided with exogenous Arg. In cells limited for
      His, increased expression of arg-2 and cpc-1, and decreased expression of cox-5,
      also had translational and transcriptional components. The arg-2 and cpc-1
      transcripts contain upstream open reading frames (uORFs), as do their
      Saccharomyces cerevisiae homologs CPA1 and GCN4. We examined the regulation of
      arg-2-lacZ reporter genes containing or lacking the uORF start codon; the
      capacity for arg-2 uORF translation appeared critical for controlling gene
      expression.

PMID- 7565673
TI  - Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding
      protein Cdc42p and its activator CDC24.
AB  - Pheromone signalling in Saccharomyces cerevisiae is mediated by the STE4-STE18 G
      protein beta gamma subunits. A possible target for the subunits is Ste20p, whose
      structural homolog, the serine/threonine kinase PAK, is activated by GTP-binding
      p21s Cdc42 and Rac1. The putative Cdc42p-binding domain of Ste20p, expressed as a
      fusion protein, binds human and yeast GTP-binding Cdc42p. Cdc42p is required for
      alpha-factor-induced activation of FUS1.cdc24ts strains defective for Cdc42p
      GDP/GTP exchange show no pheromone induction at restrictive temperatures but are
      partially rescued by overexpression of Cdc42p, which is potentiated by Cdc42p12V
      mutants. Epistatic analysis indicates that CDC24 and CDC42 lie between STE4 and
      STE20 in the pathway. The two-hybrid system revealed that Ste4p interacts with
      Cdc24p. We propose that Cdc42p plays a pivotal role both in polarization of the
      cytoskeleton and in pheromone signalling.

PMID- 7565674
TI  - Regulation of interleukin 12 p40 expression through an NF-kappa B half-site.
AB  - Interleukin 12 (IL-12) is an inducible cytokine composed of 35- and 40-kDa
      subunits that is critical for promoting T helper type 1 development and cell
      mediated immunity against pathogens. The 40-kDa subunit, expressed by activated
      macrophages and B cells, is induced by several pathogens in vivo and in vitro and
      is augmented or inhibited by gamma interferon (IFN-gamma) or IL-10, respectively.
      Control of IL-12 p40 expression is therefore important for understanding
      resistance and susceptibility to a variety of pathogens, including Leishmania
      major and perhaps human immunodeficiency virus. In this report, we provide the
      first characterization of IL-12 p40 gene regulation in macrophages. We localize
      inducible activity of the promoter to the sequence -122GGGGAATTTTA-132 not
      previously recognized to bind Rel family transcription factors. We demonstrate
      binding of this sequence to NF-kappa B (p50/p65 and p50/c-Rel) complexes in
      macrophages activated by several p40-inducing pathogens and provide functional
      data to support a role for NF-kappa B family members in IL-12 p40 activation.
      Finally, we find that IFN-gamma treatment of cells enhances this binding
      interaction, thus potentially providing a mechanism for IFN-gamma augmentation of
      IL-12 production by macrophages.

PMID- 7565675
TI  - The DNA-binding properties of two heat shock factors, HSF1 and HSF3, are induced
      in the avian erythroblast cell line HD6.
AB  - Avian cells express three heat shock transcription factor (HSF) genes
      corresponding to a novel factor, HSF3, and homologs of mouse and human HSF1 and
      HSF2. Analysis of the biochemical and cell biological properties of these HSFs
      reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has
      features which are distinct from both. HSF3 is constitutively expressed in the
      erythroblast cell line HD6, the lymphoblast cell line MSB, and embryo
      fibroblasts, and yet its DNA-binding activity is induced only upon exposure of
      HD6 cells to heat shock. Acquisition of HSF3 DNA-binding activity in HD6 cells is
      accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding
      trimer, whereas the effect of heat shock on HSF1 is oligomerization of an inert
      monomer to a DNA-binding trimer. Induction of HSF3 DNA-binding activity is
      delayed compared with that of HSF1. As occurs for HSF1, heat shock leads to the
      translocation of HSF3 to the nucleus. HSF exhibits the properties of a
      transcriptional activator, as judged from the stimulatory activity of transiently
      overexpressed HSF3 measured by using a heat shock element-containing reporter
      construct and as independently assayed by the activity of a chimeric GAL4-HSF3
      protein on a GAL4 reporter construct. These results reveal that HSF3 is
      negatively regulated in avian cells and acquires DNA-binding activity in certain
      cells upon heat shock.

PMID- 7565676
TI  - Stimulation of later functions of the yeast meiotic protein kinase Ime2p by the
      IDS2 gene product.
AB  - Ime2p is a protein kinase that is expressed only during meiosis in Saccharomyces
      cerevisiae. Ime2p stimulates early, middle, and late meiotic gene expression and
      down-regulates expression of IME1, which specifies an activator of early meiotic
      genes that acts independently of Ime2p. We have identified a new gene, IDS2 (for
      IME2-dependent signaling), which has a functional relationship to Ime2p. An ids2
      null mutation delays down-regulation of IME1 and expression of middle and late
      meiotic genes. In an ime1 null mutant that express IME2 from the GAL1 promoter
      (ime1 delta PGAL1-IME2 mutant), early meiotic gene expression depends only upon
      Ime2p. In such strains, Ids2p is dispensable for expression of the early genes
      HOP1 and SPO13 but is essential for expression of the middle and late genes SPS1,
      SPS2, and SPS100. Ids2p is also essential for the autoregulatory pathway through
      which Ime2p activates its own expression via the IME2 upstream activation
      sequences (UAS). An PGAL1-IME2 derivative that produces a truncated Ime2p
      (lacking its C-terminal 174 residues) permits IME2 UAS activation in the absence
      of Ids2p. This observation suggests that Ids2p acts upstream of Ime2p or that
      Ids2p and Ime2p act in independent, convergent pathways to stimulate IME2 UAS
      activity. Accumulation of epitope-tagged Ids2p derivatives is greatest in growing
      cells and declines during meiosis. We propose that Ids2p acts indirectly to
      modify Ime2p activity, thus permitting Ime2p to carry out later meiotic
      functions.

PMID- 7565677
TI  - Tissue-dependent expression of heat shock factor 2 isoforms with distinct
      transcriptional activities.
AB  - Heat shock factor 2 (HSF2) functions as a transcriptional regulator of heat shock
      protein gene expression in mammalian cells undergoing processes of
      differentiation and development. Our previous studies demonstrated high regulated
      expression and unusual constitutive DNA-binding activity of the HSF2 protein in
      mouse testes, suggesting that HSF2 functions to regulate heat shock protein gene
      expression in spermatogenic cells. The purpose of this study was to test whether
      HSF2 regulation in testes is associated with alterations in the HSF2 polypeptide
      expressed in testes relative to other mouse tissues. Our results show that mouse
      cells express not one but two distinct HSF2 proteins and that the levels of these
      HSF2 isoforms are regulated in a tissue-dependent manner. The testes express
      predominantly the 71-kDa HSF2-alpha isoform, while the heart and brain express
      primarily the 69-kDa HSF2-beta isoform. These isoforms are generated by
      alternative splicing of HSF2 pre-mRNA, which results in the inclusion of an 18
      amino-acid coding sequence in the HSF2-alpha mRNA that is skipped in the HSF2
      beta mRNA. HSF2 alternative splicing is also developmentally regulated, as our
      results reveal a switch in expression from the HSF2-beta mRNA isoform to the HSF2
      alpha isoform during testis postnatal developmental. Transfection analysis shows
      that the HSF2-alpha protein, the predominant isoform expressed in testis cells,
      is a more potent transcriptional activator than the HSF2-beta isoform. These
      results reveal a new mechanism for the control of HSF2 function in mammalian
      cells, in which regulated alternative splicing is used to modulate HSF2
      transcriptional activity in a tissue-dependent manner.

PMID- 7565679
TI  - Src family protein tyrosine kinases induce autoactivation of Bruton's tyrosine
      kinase.
AB  - Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically
      activated following ligation of the B-cell antigen receptor. These events are
      temporally regulated, and Btk activation follows that of various members of the
      Src family of protein tyrosine kinases, thus raising the possibility that Src
      kinases participate in the Btk activation process. We have evaluated the
      mechanism underlying Btk enzyme activation and have explored the potential
      regulatory relationship between Btk and Src protein kinases. We demonstrate in
      COS transient-expression assays that Btk can be activated through intramolecular
      autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required
      for Btk catalytic functions. Coexpression of Btk with members of the Src family
      of protein tyrosine kinases, but not Syk, led to Btk tyrosine phosphorylation and
      activation. Using a series of point mutations in Blk (a representative Src
      protein kinase) and Btk, we show that Src kinases activate Btk through an
      indirect mechanism that requires membrane association of the Src enzymes as well
      as functional Btk SH3 and SH2 domains. Our results are compatible with the idea
      that Src protein tyrosine kinases contribute to Btk activation by indirectly
      stimulating Btk intramolecular autophosphorylation.

PMID- 7565678
TI  - Transcription in the yeast rRNA gene locus: distribution of the active gene
      copies and chromatin structure of their flanking regulatory sequences.
AB  - In growing yeast cells, about half of the 150 tandemly repeated rRNA genes are
      transcriptionally active and devoid of nucleosomes. By using the intercalating
      drug psoralen as a tool to mark accessible sites along chromatin DNA in vivo, we
      found that the active rRNA gene copies are rather randomly distributed along the
      ribosomal rRNA gene locus. Moreover, results from the analysis of a single,
      tagged transcription unit in the tandem array are not consistent with the
      presence of a specific subset of active genes that is stably maintained
      throughout cell divisions. In the rRNA intergenic spacers of yeast cells, an
      enhancer is located at the 3' end of each transcription unit, 2 kb upstream of
      the next promoter. Analysis of the chromatin structure along the tandem array
      revealed a structural link between transcription units and adjacent, 3' flanking
      enhancer sequences: each transcriptionally active gene is flanked by a
      nonnucleosomal enhancer, whereas inactive, nucleosome-packed gene copies are
      followed by enhancers regularly packaged in nucleosomes. From the fact that
      nucleosome-free enhancers were also detected in an RNA polymerase I mutant
      strain, we interpret these open chromatin structures as being the result of
      specific protein-DNA interactions that can occur before the onset of
      transcription. In contrast, in this mutant strain, all of the rRNA coding
      sequences are packaged in nucleosomal arrays. This finding indicates that the
      establishment of the open chromatin conformation on the activated gene copies
      requires elongating RNA polymerase I molecules advancing through the template.

PMID- 7565681
TI  - A truncated herpes simplex virus thymidine kinase phosphorylates thymidine and
      nucleoside analogs and does not cause sterility in transgenic mice.
AB  - Dividing eukaryotic cells expressing the herpes simplex virus type 1 thymidine
      kinase (TK) gene are sensitive to the cytotoxic effect of nucleoside analogs such
      as acyclovir or ganciclovir (GCV). Transgenic mice with cell-targeted expression
      of this conditional toxin have been used to create animals with temporally
      controlled cell-specific ablation. In these animal models, which allow the study
      of the physiological importance of a cell type, males are sterile. In this study,
      we showed that this phenomenon is due to testis-specific high-level expression of
      short TK transcripts initiated mainly upstream of the second internal ATG of the
      TK gene. This expression is DNA methylation independent. To obtain a suicide gene
      that does not cause male infertility, we generated and analyzed the properties of
      a truncated TK (delta TK) lacking the sequences upstream of the second ATG. We
      showed that when expressed at sufficient levels, the functional properties of
      delta TK are similar to those of TK in terms of thymidine or GCV phosphorylation.
      This translated into a similar GCV-dependent toxicity for delta TK- or TK
      expressing cells, both in vitro and in transgenic mice. However, delta TK behaved
      differently from TK in two ways. First, it did not cause sterility in delta TK
      transgenic males. Second, low-level delta TK RNA expression did not confer
      sensitivity to GCV. The uses of delta TK in cell-specific ablation in transgenic
      mice and in gene therapy are discussed.

PMID- 7565680
TI  - Segregation of unreplicated chromosomes in Saccharomyces cerevisiae reveals a
      novel G1/M-phase checkpoint.
AB  - Saccharomyces cerevisiae dbf4 and cdc7 cell cycle mutants block initiation of DNA
      synthesis (i.e., are iDS mutants) at 37 degrees C and arrest the cell cycle with
      a 1C DNA content. Surprisingly, certain dbf4 and cdc7 strains divide their
      chromatin at 37 degrees C. We found that the activation of the Cdc28 mitotic
      protein kinase and the Dbf2 kinase occurred with the correct relative timing with
      respect to each other and the observed division of the unreplicated chromatin.
      Furthermore, the division of unreplicated chromatin depended on a functional
      spindle. Therefore, the observed nuclear division resembled a normal mitosis,
      suggesting that S. cerevisiae commits to M phase in late G1 independently of S
      phase. Genetic analysis of dbf4 and cdc7 strains showed that the ability to
      restrain mitosis during a late G1 block depended on the genetic background of the
      strain concerned, since the dbf4 and cdc7 alleles examined showed the expected
      mitotic restraint in other backgrounds. This restraint was genetically dominant
      to lack of restraint, indicating that an active arrest mechanism, or checkpoint,
      was involved. However, none of the previously described mitotic checkpoint
      pathways were defective in the iDS strains that carry out mitosis without
      replicated DNA, therefore indicating that the checkpoint pathway that arrests
      mitosis in iDS mutants is novel. Thus, spontaneous strain differences have
      revealed that S. cerevisiae commits itself to mitosis in late G1 independently of
      entry into S phase and that a novel checkpoint mechanism can restrain mitosis if
      cells are blocked in late G1. We refer to this as the G1/M-phase checkpoint since
      it acts in G1 to restrain mitosis.

PMID- 7565682
TI  - Mutation avoidance and DNA repair proficiency in Ustilago maydis are
      differentially lost with progressive truncation of the REC1 gene product.
AB  - The REC1 gene of Ustilago maydis has an uninterrupted open reading frame,
      predicted from the genomic sequence to encode a protein of 522 amino acid
      residues. Nevertheless, an intron is present, and functional activity of the gene
      in mitotic cells requires an RNA processing event to remove the intron. This
      results in a change in reading frame and production of a protein of 463 amino
      acid residues. The 3'-->5' exonuclease activity of proteins derived from the REC1
      genomic open reading frame, the intronless open reading frame, and several
      mutants was investigated. The mutants included a series of deletions constructed
      by removing restriction fragments at the 3' end of the cloned REC1 gene and a set
      of mutant alleles previously isolated in screens for radiation sensitivity. All
      of these proteins were overproduced in Escherichia coli as N-terminal
      polyhistidine-tagged fusions that were subsequently purified by immobilized metal
      affinity chromatography and assayed for 3'-->5' exonuclease activity. The results
      indicated that elimination of the C-terminal third of the protein did not result
      in a serious reduction in 3'-->5' exonuclease activity, but deletion into the
      midsection caused a severe loss of activity. The biological activity of the rec1
      1 allele, which encodes a truncated polypeptide with full 3'-->5' exonuclease
      activity, and the rec1-5 allele, which encodes a more severely truncated
      polypeptide with no exonuclease activity, was investigated. The two mutants were
      equally sensitive to the lethal effect of UV light, but the spontaneous mutation
      rate was elevated 10-fold over the wild-type rate in the rec1-1 mutant and 100
      fold in the rec1-5 mutant. The elevated spontaneous mutation rate correlated with
      the ablation of exonuclease activity, but the radiation sensitivity did not.
      These results indicate that the C-terminal portion of the Rec1 protein is not
      essential for exonuclease activity but is crucial in the role of REC1 in DNA
      damage repair.

PMID- 7565683
TI  - N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in
      response to inducers of NF-kappa B activity.
AB  - The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in
      response to extracellular stimulation is a prerequisite step in the activation of
      the transcription factor NF-kappa B. Analysis of the expression of human I kappa
      B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for
      the endogenous murine protein, exogenous I kappa B alpha is degraded in response
      to inducers of NF-kappa B activity, such as phorbol myristate acetate or
      lipopolysaccharide. In addition, pretreatment of the cells with the proteasome
      inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and,
      in agreement with previous studies, stabilizes a hyperphosphorylated form of the
      human I kappa B alpha protein. By expressing mutant forms of the human protein in
      this cell line, we have been able to delineate the sequences responsible for both
      the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our
      results show that deletion of the C terminus of the I kappa B alpha molecule up
      to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation
      and inhibits ligand-inducible degradation. Further analysis reveals that the
      inducible phosphorylation of I kappa B alpha maps to two serines in the N
      terminus of the protein (residues 32 and 36) and that the mutation of either
      residue is sufficient to abolish ligand-induced degradation, whereas both
      residues must be mutated to abolish inducible phosphorylation of the protein. We
      propose that treatment of 70Z/3 cells with either phorbol myristate acetate or
      lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and
      that these phosphorylations target the protein for rapid proteolytic degradation,
      possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to
      translocate to the nucleus and to activate gene expression.

PMID- 7565684
TI  - Glucocorticoids and protein kinase A coordinately modulate transcription factor
      recruitment at a glucocorticoid-responsive unit.
AB  - The rat tyrosine aminotransferase gene is a model system to study transcriptional
      regulation by glucocorticoid hormones. We analyzed transcription factor binding
      to the tyrosine aminotransferase gene glucocorticoid-responsive unit (GRU) at kb 
      2.5, using in vivo footprinting studies with both dimethyl sulfate and DNase I.
      At this GRU, glucocorticoid activation triggers a disruption of the nucleosomal
      structure. We show here that various regulatory pathways affect transcription
      factor binding to this GRU. The binding differs in two closely related
      glucocorticoid-responsive hepatoma cell lines. In line H4II, glucocorticoid
      induction promotes the recruitment of hepatocyte nuclear factor 3 (HNF3),
      presumably through the nucleosomal disruption. However, the footprint of the
      glucocorticoid receptor (GR) is not visible, even though a regular but transient
      interaction of the GR is necessary to maintain HNF3 binding. In contrast, in line
      FTO2B, HNF3 binds to the GRU in the absence of glucocorticoids and nucleosomal
      disruption, showing that a "closed" chromatin conformation does not repress the
      binding of certain transcription factors in a uniform manner. In FTO2B cells, the
      footprint of the GR is detectable, but this requires the activation of protein
      kinase A. In addition, protein kinase A stimulation also improves the recruitment
      of HNF3 independently of glucocorticoids and enhances the glucocorticoid response
      mediated by this GRU in an HNF3-dependent manner. In conclusion, the differences
      in the behavior of this regulatory sequence in the two cell lines show that
      various regulatory pathways are integrated at this GRU through modulation of
      interrelated events: transcription factor binding to DNA and nucleosomal
      disruption.

PMID- 7565685
TI  - A DNA methylation site in the male-specific P450 (Cyp 2d-9) promoter and binding
      of the heteromeric transcription factor GABP.
AB  - The Cyp 2d-9 gene encodes the male-specific steroid 16 alpha-hydroxylase in mouse
      liver and shares a conserved regulatory element (-100TTCCGGGC-93) with another
      male-specific Slp promoter. As shown with the Slp promoter (N. Yokomori, R.
      Moore, and M. Negishi, Proc. Natl. Acad. Sci. USA 92:1302-1306, 1995), the male
      preferential demethylation also occurs at CpG/-97 in the Cyp 2d-9 promoter. The
      transcription factor which specifically binds to the demethylated element has
      been purified. The peptide sequences reveal that the factor consists of GABP
      alpha and GABP beta 1 with Ets and Notch motifs, respectively. Both DNase I
      footprinting and gel shift assays indicate that the bacterially expressed
      glutathione S-transferase-GABP fusion proteins bind to the regulatory element
      only when CpG/-97 is demethylated. Moreover, Cyp 2d-9 promoter is trans-activated
      by coexpression of GABP proteins in HepG2 cells. Given the additional results
      that CpG/-50 of the female-specific steroid 15 alpha-hydroxylase (Cyp 2a-4)
      promoter is preferentially demethylated in the females, the sex-specific
      expressions of the P450 genes correlate very well with DNA demethylation. We also
      conclude that GABP is a methylation-sensitive transcription factor and is a
      potential transcription activator of the male-specific Cyp 2d-9 promoter.

PMID- 7565686
TI  - Stabilization of vascular endothelial growth factor mRNA by hypoxia and
      hypoglycemia and coregulation with other ischemia-induced genes.
AB  - Expression of vascular endothelial growth factor (VEGF), an endothelial cell
      specific mitogen and a potent angiogenic factor, is upregulated in response to a
      hypoxic or hypoglycemic stress. Here we show that the increase in steady-state
      levels of VEGF mRNA is partly due to transcriptional activation but mostly due to
      increase in mRNA stability. Both oxygen and glucose deficiencies result in
      extension of the VEGF mRNA half-life in a protein synthesis-dependent manner.
      Viewing VEGF as a stress-induced gene, we compared its mode of regulation with
      that of other stress-induced genes. Results showed that under nonstressed
      conditions, VEGF shares with the glucose transporter GLUT-1 a relatively short
      half-life (0.64 and 0.52 h, respectively), which is extended fourfold and more
      than eightfold, respectively, when cells are deprived of either oxygen or
      glucose. In contrast, the mRNAs of another hypoxia-inducible and hypoglycemia
      inducible gene, grp78, as well as that of HSP70, were not stabilized by these
      metabolic insults. To show that VEGF and GLUT-1 are coinduced in differentially
      stressed microenvironments, multicell spheroids representing a clonal population
      of glioma cells in which each cell layer is differentially stressed were analyzed
      by in situ hybridization. Cellular microenvironments conducive to induction of
      VEGF and GLUT-1 were completely coincidental. These findings show that two
      different consequences of tissue ischemia, namely, hypoxia and glucose
      deprivation, induce VEGF and GLUT-1 expression by similar mechanisms. These
      proteins function, in turn, to satisfy the tissue needs through expanding its
      vasculature and improving its glucose utilization, respectively.

PMID- 7565687
TI  - Identification of a candidate c-mos repressor that restricts transcription of
      germ cell-specific genes.
AB  - The c-mos proto-oncogene is specifically expressed in female and male germ cells.
      Previous studies identified a negative regulatory element (NRE) upstream of the c
      mos promoter that suppresses c-mos transcription in transfected NIH 3T3 cells. In
      this study, we used gel shift assays to detect proteins in nuclear extracts of
      NIH 3T3 cells that bind to the c-mos NRE in a sequence-specific manner. One
      protein was found to bind to a region of the NRE which was shown by site-directed
      mutagenesis to be required for suppression of c-mos transcription. This factor
      was present in nuclear extracts of several somatic cell lines and tissues but not
      in male germ cells in which c-mos is transcribed, suggesting that it is a somatic
      cell repressor of c-mos transcription. The binding site of the candidate
      repressor within the c-mos NRE consists of sequences related to putative NREs
      identified in two other male germ cell-specific genes (encoding protamine 2 and
      phosphoglycerate kinase 2). The c-mos repressor bound and could be UV cross
      linked to these protamine 2 and phosphoglycerate kinase 2 gene sequences as a
      protein with an apparent molecular mass of approximately 30 kDa. The repressor
      binding site is also conserved in two other germ cell-specific genes (encoding
      testis-specific cytochrome c and heat shock-like protein 70), suggesting that the
      c-mos repressor may be generally involved in suppressing transcription of germ
      cell-specific genes in somatic cells.

PMID- 7565688
TI  - Expression and regulation by interferon of a double-stranded-RNA-specific
      adenosine deaminase from human cells: evidence for two forms of the deaminase.
AB  - A 6,474-nucleotide human cDNA clone designated K88, which encodes double-stranded
      RNA (dsRNA)-specific adenosine deaminase, was isolated in a screen for interferon
      (IFN)-regulated cDNAs. Northern (RNA) blot analysis revealed that the K88 cDNA
      hybridized to a single major transcript of approximately 6.7 kb in human cells
      which was increased about fivefold by IFN treatment. Polyclonal antisera prepared
      against K88 cDNA products expressed in Escherichia coli as glutathione S
      transferase (GST) fusion proteins recognized two proteins by Western (immunoblot)
      analysis. An IFN-induced 150-kDa protein and a constitutively expressed 110-kDa
      protein whose level was not altered by IFN treatment were detected in human
      amnion U and neuroblastoma SH-SY5Y cell lines. Only the 150-kDa protein was
      detected in mouse fibroblasts with antiserum raised against the recombinant human
      protein; the mouse 150-kDa protein was IFN inducible. Immunofluorescence
      microscopy and cell fractionation analyses showed that the 110-kDa protein was
      exclusively nuclear, whereas the 150-kDa protein was present in both the
      cytoplasm and nucleus of human cells. The amino acid sequence deduced from the
      K88 cDNA includes three copies of the highly conserved R motif commonly found in
      dsRNA-binding proteins. Both the 150-kDa and the 110-kDa proteins prepared from
      human nuclear extracts bound to double-stranded but not to single-stranded RNA
      affinity columns. Furthermore, E. coli-expressed GST-K88 fusion proteins that
      included the R motif possessed dsRNA-binding activity. Extracts prepared either
      from K88 cDNA-transfected cells or from IFN-treated cells contained increased
      dsRNA-specific adenosine deaminase enzyme activity. These results establish that
      K88 encodes an IFN-inducible dsRNA-specific adenosine deaminase and suggest that
      at least two forms of dsRNA-specific adenosine deaminase occur in human cells.

PMID- 7565689
TI  - In-frame recombination between the yeast H(+)-ATPase isogenes PMA1 and PMA2:
      insights into the mechanism of recombination initiated by a double-strand break.
AB  - Chimeric PMA1::PMA2 sequences, placed under the control of the PMA1 promoter,
      were constructed by in vivo recombination between a gapped linearized plasmid
      containing the PMA2 gene and four different fragments of the PMA1 gene. Correct
      in-frame assembly of the PMA sequences was screened by the expression of the lacZ
      reporter gene fused to the PMA2 coding region. Restriction and sequencing
      analysis of 35 chimeras showed that in all cases, the hybrid sequences was
      obtained as fusions between continuous sequences specific to PMA1 and PMA2,
      separated by a region of identity. In all but three cases, the junction sequences
      were not located at regions of greatest identity. Strikingly, depending on the
      PMA1 fragment used, junction distribution fell into two categories. In the first,
      the junctions were scattered over several hundreds of nucleotides upstream of the
      extremity of the PMA1 fragment, while in the second, they were concentrated at
      this extremity. Analysis of the alignment of the PMA1 and PMA2 sequences suggests
      that the distribution is not related to the size of the region of identity at the
      PMA1-PMA2 boundary but depends on the degree of identity of the PMA genes
      upstream of the region of identity, the accumulation of successive mismatches
      leading to a clustered distribution of the junctions. Moreover, the introduction
      of seven closely spaced mismatches near the end of a PMA1 segment with an
      otherwise-high level of identity with PMA2 led to a significantly increased
      concentration of the junctions near this end. These data show that a low level of
      identity in the vicinity of the common boundary stretch is a strong barrier to
      recombination. In contrast, consecutive mismatches or regions of overall moderate
      identity which are located several hundreds of nucleotides upstream from the PMA1
      end do not necessarily block recombination.

PMID- 7565690
TI  - An interaction between the DNA repair factor XPA and replication protein A
      appears essential for nucleotide excision repair.
AB  - Replication protein A (RPA) is required for simian virus 40-directed DNA
      replication in vitro and for nucleotide excision repair (NER). Here we report
      that RPA and the human repair protein XPA specifically interact both in vitro and
      in vivo. Mapping of the RPA-interactive domains in XPA revealed that both of the
      largest subunits of RPA, RPA-70 and RPA-34, interact with XPA at distinct sites.
      A domain involved in mediating the interaction with RPA-70 was located between
      XPA residues 153 and 176. Deletion of highly conserved motifs within this region
      identified two mutants that were deficient in binding RPA in vitro and highly
      defective in NER both in vitro and in vivo. A second domain mediating the
      interaction with RPA-34 was identified within the first 58 residues in XPA.
      Deletion of this region, however, only moderately affects the complementing
      activity of XPA in vivo. Finally, the XPA-RPA complex is shown to have a greater
      affinity for damaged DNA than XPA alone. Taken together, these results indicate
      that the interaction between XPA and RPA is required for NER but that only the
      interaction with RPA-70 is essential.

PMID- 7565691
TI  - Roles of 1-phosphatidylinositol 3-kinase and ras in regulating translocation of
      GLUT4 in transfected rat adipose cells.
AB  - Insulin stimulates glucose transport in insulin target tissues by recruiting
      glucose transporters (primarily GLUT4) from an intracellular compartment to the
      cell surface. Previous studies have demonstrated that insulin receptor tyrosine
      kinase activity and subsequent phosphorylation of insulin receptor substrate 1
      (IRS-1) contribute to mediating the effect of insulin on glucose transport. We
      have now investigated the roles of 1-phosphatidylinositol 3-kinase (PI 3-kinase)
      and ras, two signaling proteins located downstream from tyrosine phosphorylation.
      Rat adipose cells were cotransfected with expression vectors that allowed
      transient expression of epitope-tagged GLUT4 and the other genes of interest.
      Overexpression of a mutant p85 regulatory subunit of PI 3-kinase lacking the
      ability to bind and activate the p110 catalytic subunit exerted a dominant
      negative effect to inhibit insulin-stimulated translocation of epitope-tagged
      GLUT4 to the cell surface. In addition, treatment of control cells with
      wortmannin (an inhibitor of PI 3-kinase) abolished the ability of insulin to
      recruit epitope-tagged GLUT4 to the cell surface. Thus, our data suggest that PI
      3-kinase plays an essential role in insulin-stimulated GLUT4 recruitment in
      insulin target tissues. In contrast, over-expression of a constitutively active
      mutant of ras (L61-ras) resulted in high levels of cell surface GLUT4 in the
      absence of insulin that were comparable to levels seen in control cells treated
      with a maximally stimulating dose of insulin. However, wortmannin treatment of
      cells overexpressing L61-ras resulted in only a small decrease in the amount of
      cell surface GLUT4 compared with that of the same cells in the absence of
      wortmannin. Therefore, while activated ras is sufficient to recruit GLUT4 to the
      cell surface, it does so by a different mechanism that is probably not involved
      in the mechanism by which insulin stimulates GLUT4 translocation in physiological
      target tissues.

PMID- 7565692
TI  - Mammalian DNA ligase III: molecular cloning, chromosomal localization, and
      expression in spermatocytes undergoing meiotic recombination.
AB  - Three biochemically distinct DNA ligase activities have been identified in
      mammalian cell extracts. We have recently purified DNA ligase II and DNA ligase
      III to near homogeneity from bovine liver and testis tissue, respectively. Amino
      acid sequencing studies indicated that these enzymes are encoded by the same
      gene. In the present study, human and murine cDNA clones encoding DNA ligase III
      were isolated with probes based on the peptide sequences. The human DNA ligase
      III cDNA encodes a polypeptide of 862 amino acids, whose sequence is more closely
      related to those of the DNA ligases encoded by poxviruses than to replicative DNA
      ligases, such as human DNA ligase I. In vitro transcription and translation of
      the cDNA produced a catalytically active DNA ligase similar in size and substrate
      specificity to the purified bovine enzyme. The DNA ligase III gene was localized
      to human chromosome 17, which eliminated this gene as a candidate for the cancer
      prone disease Bloom syndrome that is associated with DNA joining abnormalities.
      DNA ligase III is ubiquitously expressed at low levels, except in the testes, in
      which the steady-state levels of DNA ligase III mRNA are at least 10-fold higher
      than those detected in other tissues and cells. Since DNA ligase I mRNA is also
      present at high levels in the testes, we examined the expression of the DNA
      ligase genes during spermatogenesis. DNA ligase I mRNA expression correlated with
      the contribution of proliferating spermatogonia cells to the testes, in agreement
      with the previously defined role of this enzyme in DNA replication. In contrast,
      elevated levels of DNA ligase III mRNA were observed in primary spermatocytes
      undergoing recombination prior to the first meiotic division. Therefore, we
      suggest that DNA ligase III seals DNA strand breaks that arise during the process
      of meiotic recombination in germ cells and as a consequence of DNA damage in
      somatic cells.

PMID- 7565693
TI  - G10BP, an E1A-inducible negative regulator of Sp1, represses transcription of the
      rat fibronectin gene.
AB  - Downregulation of the fibronectin (FN) gene in a rat 3Y1 derivative cell line,
      XhoC, transformed by the adenovirus E1A and E1B genes seems to be caused by the
      induction of a negative regulator, G10BP, which binds to three G-rich sequences
      in the promoter (T. Nakamura, T. Nakajima, S. Tsunoda, S. Nakada, K. Oda, H.
      Tsurui, and A. Wada, J. Virol. 66:6436-6450, 1992). These are the G10 stretch and
      two GC boxes consisting of the G10 stretch with one internal C residue insertion.
      The recognition sequences of G10BP and Sp1 (GGGCGG) overlap in these GC boxes. To
      analyze the mechanism of the downregulation, G10BP was purified by DNA affinity
      chromatography, and its molecular mass was estimated to be about 30 kDa. The
      promoter was modified by substituting the sequence GGGG with ATCC or CTTA in
      these G-rich sequences, leaving the Sp1 motif intact, and by replacing the Sp1
      motif by the T stretch. Transcription of FN promoter-chloramphenicol
      acetyltransferase fusion genes carrying the base substitution in one or more of
      these G-rich sequences both in vivo and in vitro revealed that the base
      substitution in any G-rich sequence results in reduction of promoter activity,
      although the downstream GC box (GCd) plays a primary role. The addition of G10BP
      severely inhibited the activities of the FN promoters carrying the wild-type GCd
      in vitro, while the promoters carrying the mutant GCd were unaffected. The
      binding affinity of G10BP and Sp1 to each of the G-rich sequences, analyzed by
      gel shift assays, indicated that G10BP binds strongly to the GCd, moderately to
      the G10 stretch, and weakly to GCu, while Sp1 binds strongly to GCu, moderately
      to GCd, and weakly to the G10 stretch. Sp1 binding to GCd and the G10 stretch was
      inhibited by G10BP, while binding to GCu was unaffected. These results indicate
      that FN gene transcription is inhibited in XhoC cells primarily by exclusion of
      Sp1 binding to GCd by G10BP and that G10BP is a new class of Sp1 negative
      regulator.

PMID- 7565695
TI  - Association of p107 with Sp1: genetically separable regions of p107 are involved
      in regulation of E2F- and Sp1-dependent transcription.
AB  - The retinoblastoma-related protein p107 has been shown to be a regulator of the
      transcription factor E2F. p107 associates with E2F via its pocket region and
      represses E2F-dependent transcription. In this study, we provide evidence for a
      novel interaction between p107 and the transcription factor Sp1. We show that
      p107 can be found endogenously associated with Sp1 in the extracts of several
      different cell lines. Moreover, in transient transfection assays, expression of
      p107 represses Sp1-dependent transcription. This repression of Sp1-dependent
      transcription does not require the DNA-binding domain of Sp1. Transcription
      driven by a chimeric protein containing the Ga14 DNA-binding domain and the Sp1
      activation domains is inhibited by p107. Interestingly, unlike the repression of
      E2F-dependent transcription, the repression of Sp1-dependent transcription does
      not depend on an intact pocket region. We show that distinct regions of p107 are
      involved in the control of Sp1 and E2F.

PMID- 7565694
TI  - Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.
AB  - Leukemia results from the accumulation of multiple genetic alterations that
      disrupt the control mechanisms of normal growth and differentiation. The use of
      inbred mouse strains that develop leukemia has greatly facilitated the
      identification of genes that contribute to the neoplastic transformation of
      hematopoietic cells. BXH-2 mice develop myeloid leukemia as a result of the
      expression of an ecotropic murine leukemia virus that acts as an insertional
      mutagen to alter the expression of cellular proto-oncogenes. We report the
      isolation of a new locus, Meis1, that serves as a site of viral integration in
      15% of the tumors arising in BXH-2 mice. Meis1 was mapped to a distinct location
      on proximal mouse chromosome 11, suggesting that it represents a novel locus.
      Analysis of somatic cell hybrids segregating human chromosomes allowed
      localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain
      translocations found in human leukemias. Northern (RNA) blot analysis
      demonstrated that a Meis1 probe detected a 3.8-kb mRNA present in all BXH-2
      tumors, whereas tumors containing integrations at the Meis1 locus expressed an
      additional truncated transcript. A Meis1 cDNA clone that encoded a novel member
      of the homeobox gene family was identified. The homeodomain of Meis1 is most
      closely related to those of the PBX/exd family of homeobox protein-encoding
      genes, suggesting that Meis1 functions in a similar fashion by cooperative
      binding to a distinct subset of HOX proteins. Collectively, these results
      indicate that altered expression of the homeobox gene Meis1 may be one of the
      events that lead to tumor formation in BXH-2 mice.

PMID- 7565696
TI  - Overproduction of a truncated hepatocyte nuclear factor 3 protein inhibits
      expression of liver-specific genes in hepatoma cells.
AB  - Transcription of hepatocyte-specific genes requires the interaction of their
      regulatory regions with several nuclear factors. Among them is the hepatocyte
      nuclear factor 3 (HNF3) family, composed of the HNF3 alpha, HNF3 beta, and HNF3
      gamma proteins, which are expressed in the liver and have very similar fork head
      DNA binding domains. The regulatory regions of numerous hepatocyte-specific genes
      contain HNF3 binding sites. We examined the role of HNF3 proteins in the liver
      specific phenotype by turning off the HNF3 activity in well-differentiated mhAT3F
      hepatoma cells. Cells were stably transfected with a vector allowing the
      synthesis of an HNF3 beta fragment consisting of the fork head DNA binding domain
      without the transactivating amino- and carboxy-terminal domains. The truncated
      protein was located in the nuclei of cultured hepatoma cells and competed with
      endogenous HNF3 proteins for binding to cognate DNA sites. Overproduction of this
      truncated protein, lacking any transactivating activity, induced a dramatic
      decrease in the expression of liver-specific genes, including those for albumin,
      transthyretin, transferrin, phosphoenolpyruvate carboxykinase, and aldolase B,
      whereas the expression of the L-type pyruvate kinase gene, containing no HNF3
      binding sites, was unaltered. Neither were the concentrations of various liver
      specific transcription factors (HNF3, HNF1, HNF4, and C/EBP alpha) affected. In
      partial revertants, with a lower ratio of truncated to full-length endogenous
      HNF3 proteins, previously extinguished genes were re-expressed. Thus, the
      transactivating domains of HNF3 proteins are needed for the proper expression of
      a set of liver-specific genes but not for expression of the genes encoding
      transcription factors found in differentiated hepatocytes.

PMID- 7565697
TI  - Mutations on the DNA-binding surface of TATA-binding protein can specifically
      impair the response to acidic activators in vivo.
AB  - The TATA-binding protein (TBP) contains a concave surface that interacts
      specifically with TATA promoter elements and a convex surface that mediates
      protein-protein interactions with general and gene-specific transcription
      factors. Biochemical experiments suggest that interactions between activator
      proteins and TBP are important in stimulating transcription by the RNA polymerase
      II machinery. To gain insight into the role of TBP in mediating transcriptional
      activation in vivo, we implemented a genetic strategy in Saccharomyces cerevisiae
      that involved the use of a TBP derivative with altered specificity for TATA
      elements. By genetically screening a set of TBP mutant libraries that were biased
      to the convex surface that mediates protein-protein interactions, we identified
      TBP derivatives that are impaired in the response to three acidic activators
      (Gcn4, Gal4, and Ace1) but appear normal for constitutive polymerase II
      transcription. A genetic complementation assay indicates that the activation
      defective phenotypes reflect specific functional properties of the TBP
      derivatives rather than an indirect effect on transcription. Surprisingly, three
      of the four activation-defective mutants affect residues that directly contact
      DNA. Moreover, all four mutants are defective for TATA element binding, but they
      interact normally with an acidic activation domain and TFIIB. In addition, we
      show that a subset of TBP derivatives with mutations on the DNA-binding surface
      of TBP are also compromised in their responses to acidic activators in vivo.
      These observations suggest that interactions at the TBP-TATA element interface
      can specifically affect the response to acidic activator proteins in vivo.

PMID- 7565698
TI  - Regulation of cation transport in Saccharomyces cerevisiae by the salt tolerance
      gene HAL3.
AB  - Dynamic regulation of ion transport is essential for homeostasis as cells
      confront changes in their environment. The gene HAL3 encodes a novel component of
      this regulatory circuit in the yeast Saccharomyces cerevisiae. Overexpression of
      HAL3 improves growth of wild-type cells exposed to toxic concentrations of sodium
      and lithium and suppresses the salt sensitivity conferred by mutation of the
      calcium-dependent protein phosphatase calcineurin. Null mutants of HAL3 display
      salt sensitivity. The sequence of HAL3 gives little clue to its function.
      However, alterations in intracellular cation concentrations associated with
      changes in HAL3 expression suggest that HAL3 activity may directly increase
      cytoplasmic K+ and decrease Na+ and Li+. Cation efflux in S. cerevisiae is
      mediated by the P-type ATPase encoded by the ENA1/PMR24 gene, a putative plasma
      membrane Na+ pump whose expression is salt induced. Acting in concert with
      calcineurin, HAL3 is necessary for full activation of ENA1 expression. This
      functional complementarity is also reflected in the participation of both
      proteins in recovery from alpha-factor-induced growth arrest. Recently, HAL3 was
      isolated as a gene (named SIS2) which when overexpressed partially relieves loss
      of transcription of G1 cyclins in mutants lacking the protein phosphatase Sit4p.
      Therefore, HAL3 influences cell cycle control and ion homeostasis, acting in
      parallel to the protein phosphatases Sit4p and calcineurin.

PMID- 7565700
TI  - Bending DNA can repress a eukaryotic basal promoter and inhibit TFIID binding.
AB  - Previous studies indicated that repression by eve involves cooperative DNA
      binding and leads to the formation of a DNA loop which encompasses the DNA
      sequences normally bound by the RNA polymerase II general transcription factors.
      To test the general principle of whether bending of a basal promoter sequence can
      contribute directly to repression of transcription, a minicircle template of 245
      bp was used. In a purified transcription system, transcription from the
      minicircular DNA is greatly reduced compared with that from the identical DNA
      fragment in linear form. Transcription is also reduced when the minicircle
      contains a single-stranded nick, indicating that transcription is reduced because
      of DNA bending, rather than any constraint on supercoiling. We show that the
      reduced transcription from the minicircle in these experiments is not due to a
      reduced rate of elongation by RNA polymerase II. Rather, repression occurs, at
      least in part, because binding of the general transcription factor TFIID to the
      minicircle is strongly inhibited compared with binding to the linear DNA. We
      suggest that bending DNA may be a mechanism by which eukaryotic transcription may
      be regulated, by modulating the activity of the general transcription factors.

PMID- 7565699
TI  - Structure-function relationships of the yeast cyclin-dependent kinase Pho85.
AB  - The PHO85 gene of Saccharomyces cerevisiae encodes a cyclin-dependent kinase
      involved in both transcriptional regulation and cell cycle progression. Although
      a great deal is known concerning the structure, function, and regulation of the
      highly homologous Cdc28 protein kinase, little is known concerning these
      relationships in regard to Pho85. In this study, we constructed a series of Pho85
      Cdc28 chimeras to map the region(s) of the Pho85 molecule that is critical for
      function of Pho85 in repression of acid phosphatase (PHO5) expression. Using a
      combination of site-directed and ethyl methanesulfonate-induced mutagenesis, we
      have identified numerous residues critical for either activation of the Pho85
      kinase, interaction of Pho85 with the cyclin-like molecule Pho80, or substrate
      recognition. Finally, analysis of mutations analogous to those previously
      identified in either Cdc28 or cdc2 of Schizosaccharomyces pombe suggested that
      the inhibition of Pho85-Pho80 activity in mechanistically different from that
      seen in the other cyclin-dependent kinases.

PMID- 7565702
TI  - Functional expression of a myo-inositol/H+ symporter from Leishmania donovani.
AB  - The vast majority of surface molecules in such kinetoplastid protozoa as members
      of the genus Leishmania contain inositol and are either glycosyl inositol
      phospholipids or glycoproteins that are tethered to the external surface of the
      plasma membrane by glycosylphosphatidylinositol anchors. We have shown that the
      biosynthetic precursor for these abundant glycolipids, myo-inositol, is
      translocated across the parasite plasma membrane by a specific transporter that
      is structurally related to mammalian facilitative glucose transporters. This myo
      inositol transporter has been expressed and characterized in Xenopus laevis
      oocytes. Two-electrode voltage clamp experiments demonstrate that this protein is
      a sodium-independent electrogenic symporter that appears to utilize a proton
      gradient to concentrate myo-inositol within the cell. Immunolocalization
      experiments with a transporter-specific polyclonal antibody reveal the presence
      of this protein in the parasite plasma membrane.

PMID- 7565701
TI  - The zinc finger transcription factor Egr-1 potentiates macrophage differentiation
      of hematopoietic cells.
AB  - Previously we have shown that the zinc finger transcription factor Egr-1 is
      essential for and restricts differentiation of hematopoietic cells along the
      macrophage lineage, raising the possibility that Egr-1 actually plays a
      deterministic role in governing the development of hematopoietic precursor cells
      along the monocytic lineage. To test this hypothesis, we have taken advantage of
      interleukin-3-dependent 32Dcl3 hematopoietic precursor cells which, in addition
      to undergoing granulocytic differentiation in response to granulocyte colony
      stimulating factor, were found to be induced for limited proliferation, but not
      differentiation, by granulocyte-macrophage colony-stimulating factor. It was
      shown that ectopic expression of Egr-1 blocked granulocyte colony-stimulating
      factor-induced terminal granulocytic differentiation, consistent with previous
      findings. In addition, ectopic expression of Egr-1 endowed 32Dcl3 cells with
      ability to be induced by granulocyte-macrophage colony-stimulating factor for
      terminal differentiation exclusively along the macrophage lineage. Thus, evidence
      that Egr-1 potentiates terminal macrophage differentiation has been obtained,
      suggesting that Egr-1 plays a deterministic role in governing the development of
      hematopoietic cells along the macrophage lineage.

PMID- 7565703
TI  - The chicken HMG-17 gene is dispensable for cell growth in vitro.
AB  - HMG-17 is a highly conserved and ubiquitous nonhistone chromosomal protein that
      binds to nucleosome core particles. HMG-17 and HMG-14 form a family of
      chromosomal proteins that have been reported to bind preferentially to regions of
      active chromatin structure. To study the functional role of the single-copy
      chicken HMG-17 gene, null mutants were generated by targeted gene disruption in a
      chicken lymphoid cell line, DT40. Heterozygous and homozygous null mutant cell
      lines were generated by two independent selection strategies. Heterozygous null
      mutant lines produced about half the normal level of HMG-17 protein, and
      homozygous null lines produced no detectable HMG-17. No significant changes in
      cell phenotype were observed in cells harboring either singly or doubly disrupted
      HMG-17 genes, and no compensatory changes in HMG-14 or histone protein levels
      were observed. It is concluded that HMG-17 protein is not required for normal
      growth of avian cell lines in vitro, nor does the absence of HMG-17 protein lead
      to any major changes in cellular phenotype, at least in lymphoid cells.

PMID- 7565704
TI  - Differential regulation of Raf-1 and B-Raf and Ras-dependent activation of
      mitogen-activated protein kinase by cyclic AMP in PC12 cells.
AB  - Growth factor stimulation of the mitogen-activated protein (MAP) kinase pathway
      in fibroblasts is inhibited by cyclic AMP (cAMP) as a result of inhibition of Raf
      1. In contrast, cAMP inhibits neither nerve growth factor-induced MAP kinase
      activation nor differentiation in PC12 pheochromocytoma cells. Instead, in PC12
      cells cAMP activates MAP kinase. Since one of the major differences between the
      Ras/Raf/MAP kinase cascades of these cell types is the expression of B-Raf in
      PC12 cells, we compared the effects of cAMP on Raf-1 and B-Raf. In PC12 cells
      maintained in serum-containing medium, B-Raf was refractory to inhibition by
      cAMP, whereas Raf-1 was effectively inhibited. In contrast, both B-Raf and Raf-1
      were inhibited by cAMP in serum-starved PC12 cells. The effect of cAMP is thus
      dependent upon growth conditions, with B-Raf being resistant to cAMP inhibition
      in the presence of serum. These results were extended by studies of Rat-1
      fibroblasts into which B-Raf had been introduced by transfection. As in PC12
      cells, B-Raf was resistant to inhibition by cAMP in the presence of serum,
      whereas Raf-1 was effectively inhibited. In addition, the expression of B-Raf
      rendered Rat-1 cells resistant to the inhibitory effects of cAMP on both growth
      factor-induced activation of MAP kinase and mitogenesis. These results indicate
      that Raf-1 and B-Raf are differentially sensitive to inhibition by cAMP and that
      B-Raf expression can contribute to cell type-specific differences in the
      regulation of the MAP kinase pathway. In contrast to the situation in PC12 cells,
      cAMP by itself did not stimulate MAP kinase in B-Raf-expressing Rat-1 cells. The
      activation of MAP kinase by cAMP in PC12 cells was inhibited by the expression of
      a dominant negative Ras mutant, indicating that cAMP acts on a target upstream of
      Ras. Thus, it appears that a signaling component upstream of Ras is also require
      for cAMP stimulation of MAP kinase in PC12 cells.

PMID- 7565706
TI  - Abrogation of retinoblastoma protein function by c-Abl through tyrosine kinase
      dependent and -independent mechanisms.
AB  - The decision to enter the cell division cycle is governed by the interplay
      between growth activators and growth inhibitors. The retinoblastoma protein (RB)
      is an example of a growth inhibitor whose main function appears to be the binding
      and inactivation of key cell cycle activators. One target of RB is a proto
      oncoprotein, the c-Abl tyrosine kinase. RB binds to the ATP-binding lobe in the
      kinase domain and inhibits the nuclear pool of c-Abl in quiescent and G1 cells.
      Phosphorylation of RB at G1/S releases c-Abl, leading to the activation of this
      nuclear tyrosine kinase. In this report, we describe the construction of a mutant
      Abl, replacing the ATP-binding lobe of c-Abl with that of c-Src. The mutant
      protein AS2 is active as a tyrosine kinase and can phosphorylate Abl substrates,
      such as the C-terminal repeated domain of RNA polymerase II. AS2, however, does
      not bind to RB, and its activity is not inhibited by RB. As a result, the nuclear
      pool of AS2 is no longer cell cycle regulated. Excess AS2, but not its kinase
      defective counterpart, can overcome RB-induced growth arrest in Saos-2 cells.
      Interestingly, wild-type c-Abl, in both its kinase-active and -inactive forms,
      can also overcome RB. Furthermore, overexpression of a kinase-defective c-Abl in
      rodent fibroblasts accelerates the transition from quiescence to S phase and
      cooperates with c-Myc to induce transformation. These effects, however, do not
      occur with the kinase-defective form of AS2. Thus, the growth-stimulating
      function of the kinase-defective c-Abl is dependent on the binding and the
      abrogation of RB function. That RB function can be abolished by the
      overproduction of one of its binding proteins is consistent with the hypothesis
      that RB induces cell cycle arrest by acting as a "molecular matchmaker" to
      assemble protein complexes. Exclusive engagement of RB by one of its many targets
      is incompatible with the biological function of this growth suppressor protein.

PMID- 7565705
TI  - Structural and signaling requirements for BCR-ABL-mediated transformation and
      inhibition of apoptosis.
AB  - BCR-ABL is a deregulated tyrosine kinase expressed in Philadelphia chromosome
      positive human leukemias. Prolongation of hematopoietic cell survival by
      inhibition of apoptosis has been proposed to be an integral component of BCR-ABL
      induced chronic myelogenous leukemia. BCR-ABL elicits transformation of both
      fibroblast and hematopoietic cells and blocks apoptosis following cytokine
      deprivation in various factor-dependent cells. To elucidate the mechanisms
      whereby BCR-ABL induces transformation and blocks apoptosis in hematopoietic
      cells, we examined the biological effects of expression of a series of BCR-ABL
      mutants. Single amino acid substitutions in the GRB2 binding site (Y177F), Src
      homology 2 domain (R552L), or an autophosphorylation site in the tyrosine kinase
      domain (Y793F) do not diminish the antiapoptotic and transforming properties of
      BCR-ABL in hematopoietic cells, although these mutations were previously shown to
      drastically reduce the transforming activity of BCR-ABL in fibroblasts. A BCR-ABL
      molecule containing all three mutations (Y177F/R552L/Y793F) exhibits a severe
      decrease in transforming and antiapoptotic activities compared with the wild-type
      BCR-ABL protein in 32D myeloid progenitor cells. Ras is activated, the SHC
      adapter protein is tyrosine phosphorylated and binds GRB2, and myc mRNA levels
      are increased following expression of all kinase active BCR-ABL proteins with the
      exception of the Y177F/R552L/Y793F BCR-ABL mutant in 32D cells. We propose that
      BCR-ABL uses multiple pathways to activate Ras in hematopoietic cells and that
      this activation is necessary for the transforming and antiapoptotic activities of
      BCR-ABL. However, Ras activation is not sufficient for BCR-ABL-mediated
      transformation. A BCR-ABL deletion mutant (delta 176-427) that activates Ras and
      blocks apoptosis but has severely impaired transforming ability in 32D cells has
      been identified. These data suggest that BCR-ABL requires additional signaling
      components to elicit tumorigenic growth which are distinct from those required to
      block apoptosis.

PMID- 7565707
TI  - Regulation of the DNA-binding and transcriptional activities of Xenopus laevis
      NFI-X by a novel C-terminal domain.
AB  - The nuclear factor I (NFI) family consists of sequence-specific DNA-binding
      proteins that activate both transcription and adenovirus DNA replication. We have
      characterized three new members of the NFI family that belong to the Xenopus
      laevis NFI-X subtype and differ in their C-termini. We show that these
      polypeptides can activate transcription in HeLa and Drosophila Schneider line 2
      cells, using an activation domain that is subdivided into adjacent variable and
      subtype-specific domains each having independent activation properties in
      chimeric proteins. Together, these two domains constitute the full NFI-X
      transactivation potential. In addition, we find that the X. laevis NFI-X proteins
      are capable of activating adenovirus DNA replication through their conserved N
      terminal DNA-binding domains. Surprisingly, their in vitro DNA-binding activities
      are specifically inhibited by a novel repressor domain contained within the C
      terminal part, while the dimerization and replication functions per se are not
      affected. However, inhibition of DNA-binding activity in vitro is relieved within
      the cell, as transcriptional activation occurs irrespective of the presence of
      the repressor domain. Moreover, the region comprising the repressor domain
      participates in transactivation. Mechanisms that may allow the relief of DNA
      binding inhibition in vivo and trigger transcriptional activation are discussed.

PMID- 7565709
TI  - 9-cis retinoic acid inhibition of activation-induced apoptosis is mediated via
      regulation of fas ligand and requires retinoic acid receptor and retinoid X
      receptor activation.
AB  - T-cell hybridomas, thymocytes, and T cells can be induced to undergo apoptotic
      cell death by activation through the T-cell receptor. This process requires
      macromolecular synthesis and thus gene expression, and it has been shown to be
      influenced by factors regulating transcription. Recently, activation, T-cell
      hybridomas rapidly express the Fas/CD95 receptor and its ligand, Fas ligand
      (FasL), which interact to transduce the death signal in the activated cell.
      Retinoids, the active metabolites of vitamin A, modulate expression of specific
      target genes by binding to two classes of intracellular receptors, retinoic acid
      receptors (RARs) and retinoid X receptors (RXRs). They are potent modulators of
      apoptosis in a number of experimental models, and they have been shown to inhibit
      activation-induced apoptosis in T-cell hybridomas and thymocytes. Particularly
      effective is the prototypic pan-agonist 9-cis retinoic acid (9-cis RA), which has
      high affinity for both RARs and RXRs. We report here that 9-cis RA inhibits T
      cell receptor-mediated apoptosis in T-cell hybridomas by blocking the expression
      of Fas ligand following activation. This inhibition appears to be at the level of
      FasL mRNA, with the subsequent failure to express cell surface FasL. RAR
      selective (TTNPB) or RXR-selective (LG100268) ligands alone were considerably
      less potent than RAR-RXR pan-agonists. However, the addition of both RAR- and RXR
      selective ligands was as effective as the addition of 9-cis RA alone. The
      demonstrates that the inhibitory effect requires the ligand-mediated activation
      of both retinoid receptor signaling pathways.

PMID- 7565708
TI  - Transcriptional stimulation of the retina-specific QR1 gene upon growth arrest
      involves a Maf-related protein.
AB  - The avian neural retina (NR) is derived from proliferating neuroectodermal
      precursors which differentiate after terminal mitosis and become organized in
      cell strata. Proliferation of postmitotic NR cells can be induced by infection
      with Rous sarcoma virus (RSV) and requires the expression of a functional v-Src
      protein. QR1 is a retina-specific gene expressed exclusively at the stage of
      growth arrest and differentiation during retinal development. In NR cells
      infected with tsPA101, an RSV mutant conditionally defective in pp60v-src
      mitogenic capacity, QR1 expression is downregulated in proliferating cells at 37
      degrees C and is fully restored when the cells become quiescent as a result of
      pp60v-src inactivation at 41 degrees C. We were able to arrest proliferation of
      tsPA101-infected quail NR cells expressing an active v-Src protein by serum
      starvation at 37 degrees C. This allowed us to investigate the role of cell
      growth in regulating QR1 transcription. We report that QR1 transcription is
      stimulated in growth-arrested cells at 37 degrees C compared with that in
      proliferating cells maintained at the same temperature. Growth arrest-dependent
      stimulation of QR1 transcription requires the integrity of the A box, a
      previously characterized cis-acting element responsible for QR1 transcriptional
      stimulation upon v-Src inactivation and during retinal differentiation. We also
      show that formation of the C1 complex on the A box is increased upon growth
      arrest by serum starvation in the presence of an active v-Src oncoprotein. Thus,
      the C1 complex represents an important link between cell cycle and developmental
      control of QR1 gene transcription during NR differentiation and RSV infection. By
      using antibodies directed against different Maf proteins of the leucine zipper
      family and competition with Maf consensus site-containing oligonucleotides in a
      gel shift assay, we show that the C1 complex is likely to contain a Maf-related
      protein. We also show that a purified bacterially expressed v-Maf protein is able
      to bind the A box and that the level of a 43-kDa Maf-related protein is increased
      upon growth arrest in infected retinal cells. Moreover, ectopic expression of c
      mafI, c-mafII, and mafB cDNAs in quiescent tsPA101-infected quail NR cells is
      able to stimulate transcription of a QR1 reporter gene through the A box.
      Therefore, QR1 appears to be the first target gene for a Maf-related protein(s)
      in the NR.

PMID- 7565711
TI  - Specific binding of proteins to the noncoding strand of a crucial element of the
      variant surface glycoprotein, procyclin, and ribosomal promoters of trypanosoma
      brucei.
AB  - The variant surface glycoprotein (VSG) and procyclin promoters of Trypanosoma
      brucei recruit an RNA polymerase sharing characteristic with polymerase I, but
      there is no sequence homology between them nor between these promoters and
      ribosomal promoters. We report the detailed characterization of the VSG promoter.
      The 70-bp region upstream of the transcription start site was sufficient for full
      promoter activity. Mutational analysis revealed three short critical stretches at
      positions -61 to -59 (box 1), -38 to -35 (box 2), and -1 to +1 (start site), the
      spacing of which was essential. These elements were conserved in the promoter for
      a metacyclic VSG gene. Hybrid sequences containing box 1 of the VSG promoter and
      box 2 of the ribosomal promoter were active. A specific binding of proteins to
      the noncoding strand of box 2, but not to double-stranded DNA, occurred.
      Competition experiments indicated that these proteins also bind to the
      corresponding region of the metacyclic VSG, procyclin, and ribosomal promoters.
      Binding of such a protein, of 40 kDa, appeared to be shared by these promoters.

PMID- 7565712
TI  - Replication slippage between distant short repeats in Saccharomyces cerevisiae
      depends on the direction of replication and the RAD50 and RAD52 genes.
AB  - Small direct repeats, which are frequent in all genomes, are a potential source
      of genome instability. To study the occurrence and genetic control of repeat
      associated deletions, we developed a system in the yeast Saccharomyces cerevisiae
      that was based on small direct repeats separated by either random sequences or
      inverted repeats. Deletions were examined in the LYS2 gene, using a set of 31- to
      156-bp inserts that included inserts with no apparent potential for secondary
      structure as well as two quasipalindromes. All inserts were flanked by 6- to 9-bp
      direct repeats of LYS2 sequence, providing an opportunity for Lys+ reversion via
      precise excision. Reversions could arise by extended deletions involving either
      direct repeats or random sequences and by -1-or +2-bp frameshift mutations. The
      deletion breakpoints were always associated with short (3- to 9-bp) perfect or
      imperfect direct repeats. Compared with the POL+ strain, deletions between small
      direct repeats were increased as much as 100-fold, and the spectrum was changed
      in a temperature-sensitive DNA polymerase delta pol3-t mutant, suggesting a role
      for replication. The type of deletion depended on orientation relative to the
      origin of replication. On the basis of these results, we propose (i) that
      extended deletions between small repeats arise by replication slippage and (ii)
      that the deletions occur primarily in either the leading or lagging strand. The
      RAD50 and RAD52 genes, which are required for the recombinational repair of many
      kinds of DNA double-strand breaks, appeared to be required also for the
      production of up to 90% of the deletions arising between separated repeats in the
      pol3-t mutant, suggesting a newly identified role for these genes in genome
      stability and possibly replication.

PMID- 7565710
TI  - DNA methylation associated with repeat-induced point mutation in Neurospora
      crassa.
AB  - Repeat-induced point mutation (RIP) is a process that efficiently detects DNA
      duplications prior to meiosis in Neurospora crassa and peppers them with G:C to
      A:T mutations. Cytosine methylation is typically associated with sequences
      affected by RIP, and methylated cytosines are not limited to CpG dinucleotides.
      We generated and characterized a collection of methylated and unmethylated amRIP
      alleles to investigate the connection(s) between DNA methylation and mutations by
      RIP. Alleles of am harboring 84 to 158 mutations in the 2.6-kb region that was
      duplicated were heavily methylated and triggered de novo methylation when
      reintroduced into vegetative N. crassa cells. Alleles containing 45 and 56
      mutations were methylated in the strains originally isolated but did not become
      methylated when reintroduced into vegetative cells. This provides the first
      evidence for de novo methylation in the sexual cycle and for a maintenance
      methylation system in Neurospora cells. No methylation was detected in am alleles
      containing 8 and 21 mutations. All mutations in the eight primary alleles studied
      were either G to A or C to T, with respect to the coding strand of the am gene,
      suggesting that RIP results in only one type of mutation. We consider
      possibilities for how DNA methylation is triggered by some sequences altered by
      RIP.

PMID- 7565713
TI  - SCS1, a multicopy suppressor of hsp60-ts mutant alleles, does not encode a
      mitochondrially targeted protein.
AB  - We identified and isolated a Saccharomyces cerevisiae gene which, when
      overexpressed, suppressed the temperature-sensitive phenotype of cells expressing
      a mutant allele of the gene encoding the mitochondrial chaperonin, Hsp60. This
      gene, SCS1 (suppressor of chaperonin sixty-1), encodes a 757-amino-acid protein
      of as yet unknown function which, nonetheless, has human, rice, and
      Caenorhabditis elegans homologs with high degrees (ca. 60%) of amino acid
      sequence identity. SCS1 is not an essential gene, but SCS1-null strains do not
      grow above 37 degrees C and show some growth-related defects at 30 degrees C as
      well. This gene is expressed at both 30 and 38 degrees C, producing little or no
      differences in mRNA levels at these two temperatures. Overexpression of SCS1
      could not complement an HSP60-null allele, indicating that suppression was not
      due to the bypassing of Hsp60 activity. Of 10 other hsp60-ts alleles tested, five
      could also be suppressed by SCS1 overexpression. There were no common mutant
      phenotypes of the strains expressing these alleles that give any clue as to why
      they were suppressible while others were not. An epitope (influenza virus
      hemagglutinin)-tagged form of SCS1 in single copy complemented an SCS1-null
      allele. The Scs1-hemagglutinin protein was found to be at comparable levels and
      in similar multiply modified forms in cells growing at both 30 and 38 degrees C.
      Surprisingly, when localized either by cell fractionation procedures or by
      immunocytochemistry, these proteins were found not in mitochondria but in the
      cytosol. The overexpression of SCS1 had significant effects on the cellular
      levels of mRNAs encoding the proteins Cpn10 and Mgel, two other mitochondrial
      protein cochaperones, but not on mRNAs encoding a number of other mitochondrial
      or cytosolic proteins analyzed. The implications of these findings are discussed.

PMID- 7565714
TI  - Structure-function analysis of SH3 domains: SH3 binding specificity altered by
      single amino acid substitutions.
AB  - SH3 domains mediate intracellular protein-protein interactions through the
      recognition of proline-rich sequence motifs on cellular proteins. Structural
      analysis of the Src SH3 domain (Src SH3) complexed with proline-rich peptide
      ligands revealed three binding sites involved in this interaction: two
      hydrophobic interactions (between aliphatic proline dipeptides in the SH3 ligand
      and highly conserved aromatic residues on the surface of the SH3 domain), and one
      salt bridge (between Asp-99 of Src and an Arg three residues upstream of the
      conserved Pro-X-X-Pro motif in the ligand). We examined the importance of the
      arginine binding site of SH3 domains by comparing the binding properties of wild
      type Src SH3 and Abl SH3 with those of a Src SH3 mutant containing a mutated
      arginine binding site (D99N) and Abl SH3 mutant constructs engineered to contain
      an arginine binding site (T98D and T98D/F91Y). We found that the D99N mutation
      diminished binding to most Src SH3-binding proteins in whole cell extracts;
      however, there was only a moderate reduction in binding to a small subset of Src
      SH3-binding proteins (including the Src substrate p68). p68 was shown to contain
      two Arg-containing Asp-99-dependent binding sites and one Asp-99-independent
      binding site which lacks an Arg. Moreover, substitution of Asp for Thr-98 in Abl
      SH3 changed the binding specificity of this domain and conferred the ability to
      recognize Arg-containing ligands. These results indicate that Asp-99 is important
      for Src SH3 binding specificity and that Asp-99-dependent binding interactions
      play a dominant role in Src SH3 recognition of cellular binding proteins, and
      they suggest the existence of two Src SH3 binding mechanisms, one requiring Asp
      99 and the other independent of this residue.

PMID- 7565715
TI  - Intragenic suppression among CDC34 (UBC3) mutations defines a class of ubiquitin
      conjugating catalytic domains.
AB  - Ubiquitin-conjugating (E2) enzymes contain several regions within their catalytic
      domains that are highly conserved. However, within some of these conserved
      regions are several residues that may be used to define different classes of
      catalytic domains for the E2 enzymes. One class can be defined by the Ubc1
      protein, which contains K-65, D-90, and D-120, while the corresponding positions
      within the Cdc34 (Ubc3) protein, which defines a second class of enzymes, contain
      S-73, S-97, and S-139, respectively. The presence of these differences within
      otherwise highly conserved regions of this family suggests that these residues
      may be critical for the specificity of Cdc34 function or regulation. Therefore,
      we have constructed a series of cdc34 alleles encoding mutant proteins in which
      these serine residues have been changed to other amino acid residues, including
      alanine and aspartic acid. In vivo complementation studies showed that S-97,
      which lies near the active site C-95, is essential for Cdc34 function. The
      addition of a second mutation in CDC34, which now encoded both the S97D and S73K
      changes, restored partial function to the Cdc34 enzyme. Moreover, the deletion of
      residues 103 to 114 within Cdc34, which are not present in the Ubc1-like E2s,
      allowed the S73K/S97D mutant to function as efficiently as wild-type Cdc34
      protein. Finally, the cloning and sequencing of the temperature-sensitive alleles
      of CDC34 indicated that A-62 is also unique to the Cdc34 class of E2 enzymes and
      that mutations at this position can be detrimental to Cdc34 function. Our results
      suggest that several key residues within conserved regions of the E2 enzyme
      family genetically interact with each other and define a class of E2 catalytic
      domains.

PMID- 7565716
TI  - A phosphatidylinositol (PI) kinase gene family in Dictyostelium discoideum:
      biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologs
      during growth and development.
AB  - Three groups of phosphatidylinositol (PI) kinases convert PI into PI(3)phosphate,
      PI(4)phosphate, PI(4,5) bisphosphate, and PI(3,4,5)trisphosphate. These
      phosphoinositides have been shown to function in vesicle-mediated protein
      sorting, and they serve as second-messenger signaling molecules for regulating
      cell growth. To further elucidate the mechanism of regulation and function of
      phosphoinositides, we cloned genes encoding five putative PI kinases from
      Dictyostelium discoideum. Database analysis indicates that D. discoideum PIK1
      (DdPIK1), -2, and -3 are most closely related to the mammalian p110 PI 3-kinase,
      DdPIK5 is closest to the yeast Vps34p PI 3-kinase, and DdPIK4 is most homologous
      to PI 4-kinases. Together with other known PI kinases, a superfamily of PI kinase
      genes has been defined, with all of the encoded proteins sharing a common highly
      conserved catalytic core domain. DdPIK1, -2, and -3 may have redundant functions
      because disruption of any single gene had no effect on D. discoideum growth or
      development. However, strains in which both of the two most highly related genes,
      DdPIK1 and DdPIK2, were disrupted showed both growth and developmental defects,
      while double knockouts of DdPIK1 and DdPIK3 and DdPIK2 and DdPIK3 appear to be
      lethal. The delta Ddpik1 delta Ddpik2 null cells were smaller than wild-type
      cells and grew slowly both in association with bacteria and in axenic medium when
      attached to petri plates but were unable to grow in suspension in axenic medium.
      When delta Ddpik1 delta Ddpik2 null cells were plated for multicellular
      development, they formed aggregates having multiple tips and produced abnormal
      fruiting bodies. Antisense expression of DdPIK5 (a putative homolog of the
      Saccharomyces cerevisiae VPS34) led to a defect in the growth of D. discoideum
      cells on bacterial lawns and abnormal development. DdPIK5 complemented the
      temperature-sensitive growth defect of a Schizosaccharomyces pombe delta Svps34
      mutant strain, suggesting DdPIK5 encodes a functional homolog of yeast Vps34p.
      These observations indicate that in D. discoideum, different PI kinases regulate
      distinct cellular processes, including cell growth, development, and protein
      trafficking.

PMID- 7565717
TI  - rag-1 and rag-2 are components of a high-molecular-weight complex, and
      association of rag-2 with this complex is rag-1 dependent.
AB  - Despite the essential and synergistic functions of the rag-1 and rag-2 proteins
      in V(D)J recombination and lymphocyte development, little is known about the
      biochemical properties of the two proteins. We have developed cell lines
      expressing high levels of the rag proteins and specific, sensitive immunological
      reagents for their detection, and we have examined the physical properties of the
      rag proteins in vitro and their subcellular localizations in vivo. rag-1 is
      tightly associated with nuclear structures, requires a high salt concentration to
      maintain its solubility, and is a component of large, heterogeneously sized
      complexes. Furthermore, the presence of rag-1 alters the behavior of rag-2,
      conferring on it properties similar to those of rag-1 and changing its
      distribution in the nucleus. We demonstrate that rag-1 and rag-2 are present in
      the same complex by coimmunoprecipitation, and we provide evidence that these
      complexes contain more molecules of rag-2 than of rag-1. The demonstration of
      intracellular complexes containing rag-1 and rag-2 raises the possibility that
      interaction between these proteins is necessary for their biological function.

PMID- 7565719
TI  - Degradation of c-Fos by the 26S proteasome is accelerated by c-Jun and multiple
      protein kinases.
AB  - c-Fos is associated with c-Jun to increase the transcription of a number of
      target genes and is a nuclear proto-oncoprotein with a very short half-life. This
      instability of c-Fos may be important in regulation of the normal cell cycle.
      Here we report a mechanism for degradation of c-Fos. Coexpression of c-Fos and c
      Jun in HeLa cells caused marked increase in the instability of c-Fos, whereas v
      Fos, the retroviral counterpart of c-Fos, was stable irrespective of the
      coexpression of c-Jun. Interestingly, deletion of the C-terminal PEST region of c
      Fos, which is altered in v-Fos by a frameshift mutation, greatly enhanced its
      stability, with loss of the effect of c-Jun on its stability. c-Fos synthesized
      in vitro was degraded by the 26S proteasome in a ubiquitin-dependent fashion.
      Simple association with c-Jun had no effect on the degradation of c-Fos, but the
      additions of three protein kinases, mitogen-activated protein kinase, casein
      kinase II, and CDC2 kinase, resulted in marked acceleration of its degradation by
      the proteasome-ubiquitin system, though only in the presence of c-Jun. In
      contrast, v-Fos and c-Fos with a truncated PEST motif were not degraded,
      suggesting that they escaped from down-regulation by breakdown. These findings
      indicate a new oncogenic pathway induced by acquisition of intracellular
      stability of a cell cycle modulatory factor.

PMID- 7565718
TI  - Differential expression and function of two homologous subunits of yeast 1,3-beta
      D-glucan synthase.
AB  - 1,3-beta-D-Glucan is a major structural polymer of yeast and fungal cell walls
      and is synthesized from UDP-glucose by the multisubunit enzyme 1,3-beta-D-glucan
      synthase. Previous work has shown that the FKS1 gene encodes a 215-kDa integral
      membrane protein (Fks1p) which mediates sensitivity to the echinocandin class of
      antifungal glucan synthase inhibitors and is a subunit of this enzyme. We have
      cloned and sequenced FKS2, a homolog of FKS1 encoding a 217-kDa integral membrane
      protein (Fks2p) which is 88% identical to Fks1p. The residual glucan synthase
      activity present in strains with deletions of fks1 is (i) immunodepleted by
      antibodies prepared against FKS2 peptides, demonstrating that Fks2p is also a
      component of the enzyme, and (ii) more sensitive to the echinocandin L-733,560,
      explaining the increased sensitivity of fks1 null mutants to this drug.
      Simultaneous disruption of FKS1 and FKS2 is lethal, suggesting that Fks1p and
      Fks2p are alternative subunits with essential overlapping function. Analysis of
      FKS1 and FKS2 expression reveals that transcription of FKS1 is regulated in the
      cell cycle and predominates during growth on glucose, while FKS2 is expressed in
      the absence of glucose. FKS2 is essential for sporulation, a process which occurs
      during nutritional starvation. FKS2 is induced by the addition of Ca2+ to the
      growth medium, and this induction is completely dependent on the Ca2+/calmodulin
      dependent phosphoprotein phosphatase calcineurin. We have previously shown that
      growth of fks1 null mutants is highly sensitive to the calcineurin inhibitors
      FK506 and cyclosporin A. Expression of FKS2 from the heterologous ADH1 promoter
      results in FK506-resistant growth. Thus, the sensitivity of fks1 mutants to these
      drugs can be explained by the calcineurin-dependent transcription of FKS2.
      Moreover, FKS2 is also highly induced in response to pheromone in a calcineurin
      dependent manner, suggesting that FKS2 may also play a role in the remodeling of
      the cell wall during the mating process.

PMID- 7565720
TI  - The intergenic region between the divergently transcribed niiA and niaD genes of
      Aspergillus nidulans contains multiple NirA binding sites which act
      bidirectionally.
AB  - The niaD and niiA genes of Aspergillus nidulans, which code, respectively, for
      nitrate and nitrite reductases, are divergently transcribed, and their ATGs are
      separated by 1,200 bp. The genes are under the control of the positively acting
      NirA transcription factor, which mediates nitrate induction. The DNA binding
      domain of NirA was expressed as a fusion protein with the glutathione S
      transferase of Schistosoma japonicum. Gel shift and footprint experiments have
      shown that in the intergenic region there are four binding sites for the NirA
      transcription factor. These sites can be represented by the nonpalindromic
      consensus 5'CTCCGHGG3'. Making use of a bidirectional expression vector, we have
      analyzed the role of each of the sites in niaD and niiA expression. The sites
      were numbered from the niiA side. It appeared that site 1 is necessary for the
      inducibility of niiA only, while sites 2, 3, and to a lesser extent 4 (which is
      nearer to and strongly affects niaD) act bidirectionally. The results also
      suggest that of the 10 binding sites for the AreA protein, which mediates
      nitrogen metabolite repression, those which are centrally located are
      physiologically important. The insertion of an unrelated upstream activating
      sequence into the intergenic region strongly affected the expression of both
      genes, irrespective of the orientation in which the element was inserted.

PMID- 7565722
TI  - A central role for a single c-Myb binding site in a thymic locus control region.
AB  - Locus control regions (LCRs) are powerful assemblies of cis elements that
      organize the actions of cell-type-specific trans-acting factors. A 2.3-kb LCR in
      the human adenosine deaminase (ADA) gene first intron, which controls expression
      in thymocytes, is composed of a 200-bp enhancer domain and extended flanking
      sequences that facilitate activation from within chromatin. Prior analyses have
      demonstrated that the enhancer contains a 28-bp core region and local adjacent
      augmentative cis elements. We now show that the core contains a single critical c
      Myb binding site. In both transiently cotransfected human cells and stable
      chromatin-integrated yeast cells, c-Myb strongly transactivated reporter
      constructs that contained polymerized core sequences. c-Myb protein was strongly
      evident in T lymphoblasts in which the enhancer was active and was localized
      within discrete nuclear structures. Fetal murine thymus exhibited a striking
      concordance of endogenous c-myb expression with that of mouse ADA and human ADA
      LCR-directed transgene expression. Point mutation of the c-Myb site within the
      intact 2.3-kb LCR severely attenuated enhancer activity in transfections and LCR
      activity in transgenic thymocytes. Within the context of a complex enhancer and
      LCR, c-Myb can act as an organizer of thymocyte-specific gene expression via a
      single binding site.

PMID- 7565723
TI  - The yeast carboxyl-terminal repeat domain kinase CTDK-I is a divergent cyclin
      cyclin-dependent kinase complex.
AB  - Saccharomyces cerevisiae CTDK-I is a protein kinase complex that specifically and
      efficiently hyperphosphorylates the carboxyl-terminal repeat domain (CTD) of RNA
      polymerase II and is composed of three subunits of 58, 38, and 32 kDa. The kinase
      is essential in vivo for normal phosphorylation of the CTD and for normal growth
      and differentiation. We have now cloned the genes for the two smaller kinase
      subunits, CTK2 and CTK3, and found that they form a unique, divergent cyclin
      cyclin-dependent kinase complex with the previously characterized largest subunit
      protein CTK1, a cyclin-dependent kinase homolog. The CTK2 gene encodes a cyclin
      related protein with limited homology to cyclin C, while CTK3 shows no similarity
      to other known proteins. Copurification of the three gene products with each
      other and CTDK-I activity by means of conventional chromatography and antibody
      affinity columns has verified their participation in the complex in vitro. In
      addition, null mutations of each of the genes and all combinations thereof
      conferred very similar growth-impaired, cold-sensitive phenotypes, consistent
      with their involvement in the same function in vivo. These characterizations and
      the availability of all of the genes encoding CTDK-I and reagents derivable from
      them will facilitate investigations into CTD phosphorylation and its functional
      consequences both in vivo and in vitro.

PMID- 7565721
TI  - scid cells are deficient in Ku and replication protein A phosphorylation by the
      DNA-dependent protein kinase.
AB  - Cell mutants of the Ku nuclear DNA-binding complex are ionizing radiation
      sensitive and show V(D)J recombination defects. Ku binds and activates a
      catalytic subunit of DNA-dependent protein kinase (DNA-PK), although the
      substrates for DNA-PK are unknown. We found that scid cell extracts were
      deficient in Ku phosphorylation by DNA-PK. Human chromosome 8-complemented scid
      cells, containing the human DNA-PK catalytic subunit, restored Ku
      phosphorylation. Likewise, radiation-induced RPA hyperphosphorylation was not
      completed in scid cells compared with control or chromosome 8-reconstituted
      cells. Thus, the inactivity of DNA-PK is likely responsible for the repair and
      recombination defects in scid cells.

PMID- 7565724
TI  - Wiskott-Aldrich syndrome protein physically associates with Nck through Src
      homology 3 domains.
AB  - In the second of a series of experiments designed to identify p47nck-Src homology
      3 (SH3)-binding molecules, we report the cloning of SAKAP II (Src A box Nck
      associated protein II) from an HL60 cDNA expression library. This molecule has
      been identified as a cDNA encoding the protein product of WASP, which is mutated
      in Wiskott-Aldrich syndrome patients. Studies in vivo and in vitro demonstrated a
      highly specific interaction between the SH3 domains of p47nck and Wiskott-Aldrich
      syndrome protein. Furthermore, anti-Wiskott-Aldrich syndrome protein antibodies
      recognized a protein of 66 kDa by Western blot (immunoblot) analysis. In vitro
      translation studies identified the 66-kDa protein as the protein product of WASP,
      and subcellular fractionation experiments showed that p66WASP is mainly present
      in the cytosol fraction, although significant amounts are also present in
      membrane and nuclear fractions. The main p47nck region implicated in the
      association with p66WASP was found to be the carboxy-terminal SH3 domain.

PMID- 7565725
TI  - Collagenase expression in transgenic mouse skin causes hyperkeratosis and
      acanthosis and increases susceptibility to tumorigenesis.
AB  - In a series of transgenic mice, the human tissue collagenase gene was expressed
      in the suprabasal layer of the skin epidermis. Visually, the mice had dry and
      scaly skin which upon histological analysis revealed acanthosis, hyperkeratosis,
      and epidermal hyperplasia. At the ultrastructural level, intercellular granular
      materials were absent in the transgenic skin epidermis but contact was maintained
      through the intact desmosomes. Despite a diversity of underlying etiologies,
      similar morphological hyperproliferative changes in the epidermis are observed in
      the human skin diseases of lamellar ichthyosis, atopic dermatitis, and psoriasis.
      Subsequent experiments demonstrate that when the transgenic mouse skin was
      treated once with an initiator (7,12-dimethyl-benz[a]anthracene) and then twice
      weekly with a promoter (12-O-tetradecanoylphorbol-13-acetate), there was a marked
      increase in tumor incidence among transgenic mice compared with that among
      control littermates. These experiments demonstrate that by overexpressing the
      highly specific proteolytic enzyme collagenase, a cascade of events leading to
      profound morphological changes which augment the sensitivity of the skin towards
      carcinogenesis is initiated in the epidermis.

PMID- 7565726
TI  - Yeast RLM1 encodes a serum response factor-like protein that may function
      downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway.
AB  - The MPK1 (SLT2) gene of Saccharomyces cerevisiae encodes a mitogen-activated
      protein kinase that is regulated by a kinase cascade whose known elements are
      Pkc1 (a homolog of protein kinase C), Bck1 (Slk1) (a homolog of MEK kinase), and
      the functionally redundant Mpk1 activators Mkk1 and Mkk2 (homologs of MEK). An
      activated mutation of MKK1, MKK1P386, inhibits growth when overexpressed. This
      growth-inhibitory effect was suppressed by the mpk1 delta mutation, suggesting
      that hyperactivation of the Mpk1 pathway is toxic to cells. To search for genes
      that interact with the Mpk1 pathway, we isolated both chromosomal mutations and
      dosage suppressor genes that ameliorate the growth-inhibitory effect of
      overexpressed Mkk1P386. One of the genes identified by the analysis of
      chromosomal mutations is RLM1 (resistance to lethality of MKK1P386
      overexpression), which encodes a protein homologous to a conserved domain of the
      MADS (Mcm1, Agamous, Deficiens, and serum response factor) box family of
      transcription factors. Although rlm1 delta cells grow normally at any
      temperature, they display a caffeine-sensitive phenotype similar to that observed
      in mutants defective in BCK1, MKK1/MKK2, or MPK1. A gene fusion that provides
      Rlm1 with a transcriptional activation domain of Gal4 suppresses bck1 delta and
      mpk1 delta. A screening for dosage suppressors yielded the MSG5 genes, which
      encode a dual-specificity protein phosphatase. Our results suggest that Rlm1
      functions as a transcription factor downstream of Mpk1 that is subject to
      activation by the Mpk1 mitogen-activated protein kinase pathway.

PMID- 7565727
TI  - Accumulation of a novel spliceosomal complex on pre-mRNAs containing branch site
      mutations.
AB  - Pre-mRNA assembles into spliceosomal complexes in the stepwise pathway E-->A-->B-
      >C. We show that mutations in the metazoan branchpoint sequence (BPS) have no
      apparent effect on E complex formation but block the assembly of the A complex
      and the UV cross-linking of U2 small nuclear ribonucleoprotein particle (snRNP)
      proteins. Unexpectedly, a novel complex, designated E*, assembles on pre-mRNAs
      containing BPS mutations. Unlike the E complex, the E* complex accumulates in the
      presence of ATP. U1 snRNP and U2AF, which are tightly bound to pre-mRNA in the E
      complex, are not tightly bound in the E* complex. Significantly, previous work
      showed that U1 snRNP and U2AF become destabilized from pre-mRNA after E complex
      assembly on normal pre-mRNAs. Thus, our data are consistent with a model in which
      there are two steps in the transition from the E complex to the A complex (E-->E*
      ->A). In the first step, U1 snRNP and U2AF are destabilized in an ATP-dependent,
      BPS-independent reaction. In the second step, the stable binding of U2 snRNP
      occurs in a BPS-dependent reaction.

PMID- 7565728
TI  - Recruiting TATA-binding protein to a promoter: transcriptional activation without
      an upstream activator.
AB  - The binding of TATA-binding protein (TBP) to the TATA element is the first step
      in the initiation of RNA polymerase II transcription from many promoters in
      vitro. It has been proposed that upstream activator proteins stimulate
      transcription by recruiting TBP to the promoter, thus facilitating the assembly
      of a transcription complex. However, the role of activator proteins acting at
      this step to stimulate transcription in vivo remains largely speculative. To test
      whether recruitment of TBP to the promoter is sufficient for transcriptional
      activation in vivo, we constructed a hybrid protein containing TBP of the yeast
      Saccharomyces cerevisiae fused to the DNA-binding domain of GAL4. Our results
      show that TBP recruited by the GAL4 DNA-binding domain to promoters bearing a
      GAL4-binding site can interact with the TATA element and direct high levels of
      transcription. This finding indicates that binding of TBP to promoters in S.
      cerevisiae is a major rate-limiting step accelerated by upstream activator
      proteins.

PMID- 7565729
TI  - Targeted disruption of the NIT8 gene in Chlamydomonas reinhardtii.
AB  - We have used homologous recombination to disrupt the nuclear gene NIT8 in
      Chlamydomonas reinhardtii. This is the first report of targeted gene disruption
      of an endogenous locus in C. reinhardtii and only the second for a photosynthetic
      eukaryote. NIT8 encodes a protein necessary for nitrate and nitrite assimilation
      by C. reinhardtii. A disruption vector was constructed by placing the CRY1-1
      selectable marker gene, which confers emetine resistance, within the NIT8 coding
      region. nit8 mutants are unable to grow on nitrate as their sole nitrogen source
      (Nit-) and are resistant to killing by chlorate. One of 2,000 transformants
      obtained after selection on emetine-chlorate medium contained a homologous
      insertion of five copies of the disruption plasmid into the NIT8 gene, producing
      an emetine-resistant, chlorate-resistant Nit- phenotype. The mutant phenotype was
      rescued by the wild-type NIT8 gene upon transformation. Seven other mutations at
      the nit8 locus, presumably resulting from homologous recombination with the
      disruption plasmid, were identified but were shown to be accompanied by deletions
      of the surrounding genomic region.

PMID- 7565730
TI  - The cellular response to neuregulins is governed by complex interactions of the
      erbB receptor family.
AB  - Deregulated signaling by the four members of the epidermal growth factor receptor
      tyrosine kinase family (erbB family) is implicated in the genesis or progression
      of human cancers. However, efforts to analyze signaling by these receptors have
      been hampered by the diversity of ligands and extensive interreceptor cross talk.
      We have expressed the four human erbB family receptors, singly and in pairwise
      combinations, in a pro-B-lymphocyte cell line (Ba/F3) and investigated the range
      of interactions activated by the epidermal growth factor homology domain of the
      agonist neuregulin beta. The results provide the first comprehensive analysis of
      the response of this receptor family to a single peptide agonist. This peptide
      induced complex patterns of receptor tyrosine phosphorylation and regulation of
      Ba/F3 cell survival and proliferation. These data demonstrate the existence of
      several previously undocumented receptor interactions driven by neuregulin.

PMID- 7565731
TI  - mRNA decay mediated by two distinct AU-rich elements from c-fos and granulocyte
      macrophage colony-stimulating factor transcripts: different deadenylation
      kinetics and uncoupling from translation.
AB  - Poly(A) tail removal is a critical first step in the decay pathway for many yeast
      and mammalian mRNAs. Poly(A) shortening rates can be regulated by cis-acting
      sequences within the transcribed portion of mRNA, which in turn control mRNA
      turnover rates. The AU-rich element (ARE), found in the 3' untranslated regions
      of many highly labile mammalian mRNAs, is a well-established example of this type
      of control. It represents the most widespread RNA stability determinant among
      those characterized in mammalian cells. Here, we report that two structurally
      different AREs, the c-fos ARE and the granulocyte-macrophage colony-stimulating
      factor (GM-CSF) ARE, both direct rapid deadenylation as the first step in mRNA
      degradation, but by different kinetics. For c-fos-ARE-mediated decay, the mRNA
      population undergoes synchronous poly(A) shortening and is deadenylated at the
      same rate, implying the action of distributive or nonprocessive ribonucleolytic
      digestion of poly(A) tails. In contrast, the population of granulocyte-macrophage
      colony-stimulating factor ARE-containing mRNAs is deadenylated asynchronously,
      with the formation of fully deadenylated intermediates, consistent with the
      action of processive ribonucleolytic digestion of poly(A) tails. An important
      general implication of this finding is that different RNA-destabilizing elements
      direct deadenylation either by modulating the processivity at which a single
      RNase functions or by recruiting kinetically distinct RNases. We have also
      employed targeted inhibition of translation initiation to demonstrate that the
      RNA-destabilizing function of both AREs can be uncoupled from translation by
      ribosomes. In addition, a blockade of ongoing transcription has been used to
      further probe the functional similarities and distinctions of these two AREs. Our
      data suggest that the two AREs are targets of two distinct mRNA decay pathways. A
      general model for ARE-mediated mRNA degradation involving a potential role for
      certain heterogeneous nuclear ribonucleoproteins and ARE-binding proteins is
      proposed.

PMID- 7565732
TI  - Transcriptional repression of the interleukin-2 gene by vitamin D3: direct
      inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor.
AB  - T-lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3], the active metabolite of vitamin D3, and is associated with a
      decrease in interleukin 2 (IL-2), gamma interferon, and granulocyte-macrophage
      colony-stimulating factor mRNA levels. We report here that 1,25(OH)2D3-mediated
      repression in Jurkat cells is cycloheximide resistant, suggesting that it is a
      direct transcriptional repressive effect on IL-2 expression by the vitamin D3
      receptor (VDR). We therefore examined vitamin D3-mediated repression of activated
      IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter
      constructs and a VDR overexpression vector and by DNA binding. We delineated an
      element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3
      mediated repression in vivo to a short 40-bp region encompassing an important
      positive regulatory element, NF-AT-1, which is bound by a T-cell-specific
      transcription factor, NFATp, as well as by AP-1. VDR DNA-binding mutants were
      unable to either bind to this element in vitro or repress in vivo; the VDR DNA
      binding domain alone, however, bound the element but also could not repress IL-2
      expression. These results indicate that DNA binding by VDR is necessary but not
      sufficient to mediate IL-2 repression. By combining partially purified proteins
      in vitro, we observed the loss of the bound NFATp/AP-1-DNA complex upon inclusion
      of VDR or VDR-retinoid X receptor. Order of addition and off-rate experiments
      indicate that the VDR-retinoid X receptor heterodimer blocks NFATp/AP-1 complex
      formation and then stably associates with the NF-AT-1 element. This direct
      inhibition by a nuclear hormone receptor of transcriptional activators of the IL
      2 gene may provide a mechanistic explanation of how vitamin derivatives can act
      as potent immunosuppressive agents.

PMID- 7565733
TI  - Role of pRb-related proteins in simian virus 40 large-T-antigen-mediated
      transformation.
AB  - Simian virus 40 large T-antigen (TAg) transformation is thought to be mediated,
      at least in part, by binding to and modulating the function of certain cellular
      proteins, including the retinoblastoma tumor suppressor gene product, pRb. TAg
      can disrupt the inhibitory complexes formed by pRb with the oncogenic
      transcription factor E2F, and this mechanism has been suggested to be important
      for TAg-mediated transformation. Residues 102 to 114 of TAg (including the LXCXE
      motif) are required for binding to pRb. Mutations within this LXCXE motif abolish
      the ability of TAg to bind to pRb as well as to transform certain cell types. TAg
      can also bind to at least two other cellular proteins, p107 and p130, that are
      related to pRb by sequence homology and share the ability to bind E2F. However,
      whether p107 and p130 are also targets in TAg-mediated transformation is less
      clear. To assess the relative contribution of the inactivation of pRb, p107, and
      p130 to transformation by TAg, fibroblasts were prepared from embryos derived
      from matings of mice heterozygous for an Rb knockout allele. The ability of TAg
      to transform fibroblasts homozygous for either wild-type or knockout Rb alleles
      was evaluated. It is demonstrated that the integrity of the LXCXE motif provides
      a growth advantage in Rb+/+ and Rb-/- cells. Furthermore, wild-type TAg, but not
      the LXCXE mutants, could bind to p107 and p130 and disrupt p107-E2F and p130-E2F
      binding complexes. These results suggest that p107 and p130 participate in TAg
      mediated transformation and that they may behave as tumor suppressors.

PMID- 7565734
TI  - The pentapeptide motif of Hox proteins is required for cooperative DNA binding
      with Pbx1, physically contacts Pbx1, and enhances DNA binding by Pbx1.
AB  - The vertebrate Hox genes, which represent a subset of all homeobox genes, encode
      proteins that regulate anterior-posterior positional identity during
      embryogenesis and are cognates of the Drosophila homeodomain proteins encoded by
      genes composing the homeotic complex (HOM-C). Recently, we demonstrated that
      multiple Hox proteins bind DNA cooperatively with both Pbx1 and its oncogenic
      derivative, E2A-Pbx1. Here, we show that the highly conserved pentapeptide motif
      F/Y-P-W-M-R/K, which occurs in numerous Hox proteins and is positioned 8 to 50
      amino acids N terminal to the homeodomain, is essential for cooperative DNA
      binding with Pbx1 and E2A-Pbx1. Point mutational analysis demonstrated that the
      tryptophan and methionine residues within the core of this motif were critical
      for cooperative DNA binding. A peptide containing the wild-type pentapeptide
      sequence, but not one in which phenylalanine was substituted for tryptophan,
      blocked the ability of Hox proteins to bind cooperatively with Pbx1 or E2A-Pbx1,
      suggesting that the pentapeptide itself provides at least one surface through
      which Hox proteins bind Pbx1. Furthermore, the same peptide, but not the mutant
      peptide, stimulated DNA binding by Pbx1, suggesting that interaction of Hox
      proteins with Pbx1 through the pentapeptide motif raises the DNA-binding ability
      of Pbx1.

PMID- 7565735
TI  - Correlation of two-hybrid affinity data with in vitro measurements.
AB  - Since their introduction, the interaction trap and other two-hybrid systems have
      been used to study protein-protein interactions. Despite their general use,
      little is known about the extent to which the degree of protein interaction
      determined by two-hybrid approaches parallels the degree of interaction
      determined by biochemical techniques. In this study, we used a set of lexAop-LEU2
      and lexAop-lacZ reporters to calibrate the interaction trap. For the calibration,
      we used two sets of proteins, the Myc-Max-Mxi1 helix-loop-helix proteins, and
      wild-type and dimerization-defective versions of the lambda cI repressor. Our
      results indicate that the strength of interaction as predicted by the two-hybrid
      approach generally correlates with that determined in vitro, permitting
      discrimination of high-, intermediate-, and low-affinity interactions, but there
      was no single reporter for which the amount of gene expression linearly reflected
      affinity measured in vitro. However, some reporters showed thresholds and only
      responded to stronger interactions. Finally, some interactions were subject to
      directionality, and their apparent strength depended on the reporter used. Taken
      together, our results provide a cautionary framework for interpreting affinities
      from two-hybrid experiments.

PMID- 7565737
TI  - Evidence for a G2 checkpoint in p53-independent apoptosis induction by X
      irradiation.
AB  - The p53 tumor suppressor gene is thought to be required for the induction of
      programmed cell death (apoptosis) initiated by DNA damage. We show here, however,
      that the human promyelocytic leukemia cell line HL-60, which is known to be
      deficient in p53 because of large deletions in the p53 gene, can be induced to
      undergo apoptosis following X-irradiation. We demonstrate that the decision to
      undergo apoptosis in this cell line appears to be made at a G2 checkpoint. In
      addition, we characterize an HL-60 variant, HCW-2, which is radioresistant. HCW-2
      cells display DNA damage induction and repair capabilities identical to those of
      the parental HL-60 cell line. Thus, the difference between the two cell lines
      appears to be that X-irradiation induces apoptosis in HL-60, but not in HCW-2,
      cells. Paradoxically, HCW-2 cells display high levels of expression of bax, which
      enhances apoptosis, and no longer express bcl-2, which blocks apoptosis. HCW-2
      cells' resistance to apoptosis may be due to the acquisition of expression of bcl
      XL, a bcl-2-related inhibitor of apoptosis. In summary, apoptosis can be induced
      in X-irradiated HL-60 cells by a p53-independent mechanism at a G2 checkpoint,
      despite the presence of endogenous bcl-2. The resistance shown by HCW-2 cells
      suggests that bcl-XL can block this process.

PMID- 7565736
TI  - PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage
      colony-stimulating factor receptor alpha gene.
AB  - Growth factor receptors play an important role in hematopoiesis. In order to
      further understand the mechanisms directing the expression of these key
      regulators of hematopoiesis, we initiated a study investigating the transcription
      factors activating the expression of the granulocyte-macrophage colony
      stimulating factor (GM-CSF) receptor alpha gene. Here, we demonstrate that the
      human GM-CSF receptor alpha promoter directs reporter gene activity in a tissue
      specific fashion in myelomonocytic cells, which correlates with its expression
      pattern as analyzed by reverse transcription PCR. The GM-CSF receptor alpha
      promoter contains an important functional site between positions -53 and -41 as
      identified by deletion analysis of reporter constructs. We show that the myeloid
      and B cell transcription factor PU.1 binds specifically to this site.
      Furthermore, we demonstrate that a CCAAT site located upstream of the PU.1 site
      between positions -70 and -54 is involved in positive-negative regulation of the
      GM-CSF receptor alpha promoter activity. C/EBP alpha is the major CCAAT/enhancer
      binding protein (C/EBP) form binding to this site in nuclear extracts of U937
      cells. Point mutations of either the PU.1 site or the C/EBP site that abolish the
      binding of the respective factors result in a significant decrease of GM-CSF
      receptor alpha promoter activity in myelomonocytic cells only. Furthermore, we
      demonstrate that in myeloid and B cell extracts, PU.1 forms a novel, specific,
      more slowly migrating complex (PU-SF) when binding the GM-CSF receptor alpha
      promoter PU.1 site. This is the first demonstration of a specific interaction
      with PU.1 on a myeloid PU.1 binding site. The novel complex is distinct from that
      described previously as binding to B cell enhancer sites and can be formed by
      addition of PU.1 to extracts from certain nonmyeloid cell types which do not
      express PU.1, including T cells and epithelial cells, but not from erythroid
      cells. Furthermore, we demonstrate that the PU-SF complex binds to PU.1 sites
      found on a number of myeloid promoters, and its formation requires an intact PU.1
      site adjacent to a single-stranded region. Expression of PU.1 in nonmyeloid cells
      can activate the GM-CSF receptor alpha promoter. Deletion of the amino-terminal
      region of PU.1 results in a failure to form the PU-SF complex and in a
      concomitant loss of transactivation, suggesting that formation of the PU-SF
      complex is of functional importance for the activity of the GM-CSF receptor alpha
      promoter. Finally, we demonstrate that C/EBP alpha can also active the GM-CSF
      receptor alpha promoter in nonmyeloid cells. These results suggest that PU.1 and
      C/EBP alpha direct the cell-type-specific expression of GM-CSF receptor alpha,
      further establish the role of PU.1 as a key regulator of hematopoiesis, and point
      to C/EBP alpha as an additional important factor in this process.

PMID- 7565738
TI  - Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers
      for different classes of nuclear receptors.
AB  - We describe here a novel class of cis-acting response elements for retinoid,
      vitamin D, and estrogen receptors which are widely spaced (10 to 200 bp) direct
      repeats (DRs) of the canonical 5'-AGGTCA half-site recognition motif (DR10 to
      DR200). In contrast to the specificity previously observed with shortly spaced
      DRs (DR1 to DR5), the different receptors bind promiscuously to these novel
      elements to activate transcription in the presence of retinoic acid (RA), vitamin
      D, or estrogen. The greatest RA-dependent transactivation, seen with DR15, was
      similar to that observed with the canonical DR5. Both RA receptors and retinoid X
      receptors contribute to transactivation through widely spaced DR elements. With
      the estrogen receptor, DR15 was one-third as efficient as the classical
      palindromic response element. A further increase of spacer lengths progressively
      decreased the efficiency of transactivation. No transactivation was seen with
      widely spaced DRs when the thyroid and retinoid X receptors were coexpressed in
      the presence of their ligands. The progesterone receptor was also unable to
      transactivate through a DR10 element composed of its cognate binding motifs.
      These results considerably extend the response element repertoire of nuclear
      receptors and suggest the existence of promiscuous transcriptional regulation
      through common response elements, as well as the possibility of receptor "cross
      talk."

PMID- 7565740
TI  - Endocytosis and vacuolar degradation of the plasma membrane-localized Pdr5 ATP
      binding cassette multidrug transporter in Saccharomyces cerevisiae.
AB  - Multidrug resistance (MDR) to different cytotoxic compounds in the yeast
      Saccharomyces cerevisiae can arise from overexpression of the Pdr5 (Sts1, Ydr1,
      or Lem1) ATP-binding cassette (ABC) multidrug transporter. We have raised
      polyclonal antibodies recognizing the yeast Pdr5 ABC transporter to study its
      biogenesis and to analyze the molecular mechanisms underlying MDR development.
      Subcellular fractionation and indirect immunofluorescence experiments showed that
      Pdr5 is localized in the plasma membrane. In addition, pulse-chase radiolabeling
      of cells and immunoprecipitation indicated that Pdr5 is a short-lived membrane
      protein with a half-life of about 60 to 90 min. A dramatic metabolic
      stabilization of Pdr5 was observed in delta pep4 mutant cells defective in
      vacuolar proteinases, and indirect immunofluorescence showed that Pdr5
      accumulates in vacuoles of stationary-phase delta pep4 mutant cells,
      demonstrating that Pdr5 turnover requires vacuolar proteolysis. However, Pdr5
      turnover does not require a functional proteasome, since the half-life of Pdr5
      was unaffected in either pre1-1 or pre1-1 pre2-1 mutants defective in the
      multicatalytic cytoplasmic proteasome that is essential for cytoplasmic protein
      degradation. Immunofluorescence analysis revealed that vacuolar delivery of Pdr5
      is blocked in conditional end4 endocytosis mutants at the restrictive
      temperature, showing that endocytosis delivers Pdr5 from the plasma membrane to
      the vacuole.

PMID- 7565739
TI  - Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta)
      through direct interaction with RAR beta.
AB  - Transcription regulation by DNA-bound activators is thought to be mediated by a
      direct interaction between these proteins and TATA-binding protein (TBP), TFIIB,
      or TBP-associated factors, although occasionally cofactors or adapters are
      required. For ligand-induced activation by the retinoic acid receptor-retinoid X
      receptor (RAR-RXR) heterodimer, the RAR beta 2 promoter is dependent on the
      presence of E1A or E1A-like activity, since this promoter is activated by
      retinoic acid only in cells expressing such proteins. The mechanism underlying
      this E1A requirement is largely unknown. We now show that direct interaction
      between RAR and E1A is a requirement for retinoic acid-induced RAR beta 2
      activation. The activity of the hormone-dependent activation function 2 (AF-2) of
      RAR beta is upregulated by E1A, and an interaction between this region and E1A
      was observed, but not with AF-1 or AF-2 of RXR alpha. This interaction is
      dependent on conserved region III (CRIII), the 13S mRNA-specific region of E1A.
      Deletion analysis within this region indicated that the complete CRIII is needed
      for activation. The putative zinc finger region is crucial, probably as a
      consequence of interaction with TBP. Furthermore, the region surrounding amino
      acid 178, partially overlapping with the TBP binding region, is involved in both
      binding to and activation by AF-2. We propose that E1A functions as a cofactor by
      interacting with both TBP and RAR, thereby stabilizing the preinitiation complex.

PMID- 7565741
TI  - The activity of transcription factor PBP, which binds to the proximal sequence
      element of mammalian U6 genes, is regulated during differentiation of F9 cells.
AB  - Mouse F9 embryonic carcinoma (EC) cells differentiate in culture to parietal
      endoderm (PE) cells upon induction with retinoic acid and cyclic AMP. In the
      course of this process, the expression of polymerase III transcripts, e.g., 5S
      rRNA and U6 small nuclear RNA, is dramatically reduced. This reduction of
      endogenous RNA content is accompanied by a loss of transcriptional capacity in
      cell extracts from PE cells. Partial purification of such extracts reveals that
      the DNA-binding activity of transcription factor PBP, binding specifically to the
      proximal sequence element (PSE) sequence of vertebrate U6 genes, is significantly
      reduced. This finding is corroborated by a loss in the transcriptional activity
      of this factor in reconstitution assays with partially purified polymerase III
      transcription components. In contrast, the activity of TFIIIA and TFIIIB and the
      amount of free TATA-binding protein remain unchanged during the differentiation
      process analyzed here. These data show for the first time that the PSE-binding
      protein PBP is essentially involved in the differential regulation of polymerase
      III genes governed by external promoters.

PMID- 7565743
TI  - Core promoter specificities of the Sp1 and VP16 transcriptional activation
      domains.
AB  - The core promoter compositions of mammalian protein-coding genes are highly
      variable; some contain TATA boxes, some contain initiator (Inr) elements, and
      others contain both or neither of these basal elements. The underlying reason for
      this heterogeneity remains a mystery, as recent studies have suggested that TATA
      containing and Inr-containing core promoters direct transcription initiation by
      similar mechanisms and respond similarly to a wide variety of upstream
      activators. To analyze in greater detail the influence of core promoter structure
      on transcriptional activation, we compared activation by GAL4-VP16 and Sp1
      through synthetic core promoters containing a TATA box, an Inr, or both TATA and
      Inr. Striking differences were found between the two activators, most notably in
      the relative strengths of the TATA/Inr and Inr core promoters: the TATA/Inr
      promoter was much stronger than the Inr promoter when transcription was activated
      by GAL4-VP16, but the strengths of the two promoters were more comparable when
      transcription was activated by Sp1. To define the domains of Sp1 responsible for
      efficient activation through an Inr, several Sp1 deletion mutants were tested as
      GAL4 fusion proteins. The results reveal that the glutamine-rich activation
      domains, which previously were found to interact with Drosophila TAF110,
      preferentially stimulate Inr-containing core promoters. In contrast, efficient
      activation through TATA appears to require additional domains of Sp1. These
      results demonstrate that activation domains differ in their abilities to function
      with specific core promoters, suggesting that the core promoter structure found
      in a given gene may reflect a preference of the regulators of that gene.
      Furthermore, the core promoter preference of an activation domain may be related
      to a specific mechanism of action, which may provide a functional criterion for
      grouping activation domains into distinct classes.

PMID- 7565742
TI  - Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in
      mice.
AB  - The mouse W locus encodes Kit, the receptor tyrosine kinase for stem cell factor
      (SCF). Kit is required for several developmental processes, including the
      proliferation and survival of melanoblasts. Because of the nearly complete
      failure of Wrio/+ melanoblasts to colonize the skin, the costs of Wrio/+ mice are
      characterized by a majority of white hairs interspersed among pigmented hairs,
      giving a roan effect. However, 3.6% of Wrio/+ mice exhibit phenotypic reversions,
      i.e., spots of wild-type color on their coats with an otherwise mutant phenotype.
      Melanocyte cell lines were derived from each of six independent reversion spots
      on the skin of (C57BL/6 x DBA/2)F1 Wrio/+ mice. All six melanocyte cell lines
      exhibited the general characteristics common to normal, nonimmortal mouse
      melanocytes. Of these, three revertant cell lines had lost the dominant-negative
      Wrio allele following mitotic recombination between the centromere and the W
      locus. One of the cell lines remained Wrio/+ but showed (i) stimulation in
      response to SCF and (ii) increased Kit expression, suggesting that the Wrio
      mutation can be rescued by increased endogenous expression of the c-kit proto
      oncogene. Finally, two cell lines showed no detectable genetic change at the
      W/Kit locus and failed to respond to SCF stimulation in vitro. These results
      demonstrate that mitotic recombination can create large patches of wild-type hair
      on the coats of Wrio/+ mutant mice. This shows that mitotic recombination occurs
      spontaneously in normal healthy tissue in vivo. Moreover, these experiments
      confirm that other mechanisms, not associated with loss of heterozygosity, may
      account for the coat color reversion phenotype.

PMID- 7565745
TI  - The release element of the yeast polymerase I transcription terminator can
      function independently of Reb1p.
AB  - The Saccharomyces cerevisiae polymerase I (polI) transcription terminator
      utilizes a DNA-binding protein (Reb1p) as part of a signal that causes the
      polymerase to pause prior to release from the template. To study the release
      element of the terminator, independent of the Reb1p pause signal, we have
      replaced the Reb1p binding site with the binding site for the lac repressor,
      which acts as a self-contained heterologous pause signal for polI. Release
      efficiency is maximal when the lac repressor causes polI to pause in exactly the
      same position that Reb1p would have caused it to pause, suggesting that polI must
      be precisely positioned for transcript release to occur. Mutational analysis
      shows that the release element is a region rich in T residues which codes for the
      extreme 3' end of the transcript and which has no apparent ability to form
      hairpins when transcribed into RNA. We discuss possible mechanisms whereby this
      polI release element might function.

PMID- 7565744
TI  - Mcm1 is required to coordinate G2-specific transcription in Saccharomyces
      cerevisiae.
AB  - In the budding yeast Saccharomyces cerevisiae, MCM1 encodes an essential DNA
      binding protein that regulates transcription of many genes in cooperation with
      different associated factors. With the help of a conditional expression system,
      we show that Mcm1 depletion has a distinct effect on cell cycle progression by
      preventing cells from undergoing mitosis. Genes that normally exhibit a G2-to-M
      phase-specific expression pattern, such as CLB1, CLB2, CDC5, SWI5, and ACE2,
      remain uninduced in the absence of functional Mcm1. In vivo footprinting
      experiments show that Mcm1, in conjunction with an Mcm1-recruited factor, binds
      to the promoter regions of SWI5 and CLB2 at sites shown to be involved in cell
      cycle regulation. However, promoter occupation at these sites is cell cycle
      independent, and therefore the regulatory system seems to operate on
      constitutively bound Mcm1 complexes. A gene fusion that provides Mcm1 with a
      strong transcriptional activation domain causes transcription of SWI5, CLB1,
      CLB2, and CDC5 at inappropriate times of the cell cycle. Thus, Mcm1 and a
      cooperating, cell cycle-regulated activation partner are directly involved in the
      coordinated expression of multiple G2-regulated genes. The arrest phenotype of
      Mcm1-depleted cells is consistent with low levels of Clb1 and Clb2 kinase.
      However, constitutive CLB2 expression does not suppress the mitotic defect, and
      therefore other essential activities required for the G2-to-M transition must
      also depend on Mcm1 function.

PMID- 7565746
TI  - Requirement of the SH3 and SH2 domains for the inhibitory function of tyrosine
      protein kinase p50csk in T lymphocytes.
AB  - Previous studies from our laboratory have shown that the cytosolic tyrosine
      protein kinase p50csk is involved in the negative regulation of T-cell activation
      (L.M. L. Chow, M. Fournel, D. Davidson, and A. Veillette, Nature [London] 365:156
      160, 1993). This function most probably reflects the ability of Csk to
      phosphorylate the inhibitory carboxy-terminal tyrosine of p56lck and p59fynT, two
      Src-related enzymes abundantly expressed in T lymphocytes. Herein, we have
      attempted to better understand the mechanisms by which Csk participates in the
      inhibitory phase of T-cell receptor signalling. Our results demonstrated that the
      Src homology 3 (SH3) and SH2 domains of p50csk are crucial for its negative
      impact on T-cell receptor-mediated signals. As these two sequences were not
      essential for phosphorylation of the carboxy-terminal tyrosine of a Src-like
      product in yeast cells, we postulated that they mediate protein-protein
      interactions allowing the recruitment of p50csk in the vicinity of activated Lck
      and/or FynT in T cells. In complementary studies, it was observed that linkage of
      a constitutive membrane targeting signal to the amino terminus of Csk rescued the
      deleterious impact of a point mutation in the SH2 domain of p50csk. This
      observation suggested that the SH2 sequence is in part necessary to translocate
      p50csk from the cytoplasm to the plasma membrane, where Src-related enzymes are
      located. Nevertheless, constitutive membrane localization was unable to correct
      the effect of complete deletion of the SH3 or SH2 sequence, implying that these
      domains provide additional functions necessary for the biological activity of
      p50csk.

PMID- 7565747
TI  - Transcriptional regulation of metacyclic variant surface glycoprotein gene
      expression during the life cycle of Trypanosoma brucei.
AB  - In antigenic variation in African trypanosomes, switching of the variant surface
      glycoprotein (VSG) allows evasion of the mammalian host immune response.
      Trypanosomes first express the VSG in the tsetse fly vector, at the metacyclic
      stage, in preparation for transfer into the mammal. In this life cycle stage, a
      small, specific subset (1 to 2%) of VSGs are activated, and we have shown
      previously that the system of activation and expression of metacyclic VSG (M-VSG)
      genes is very different from that used for bloodstream VSG genes (S.V. Graham,
      K.R. Matthews, P.G. Shiels, and J.D. Barry, Parasitology 101:361-367, 1990). Now
      we show that unlike other trypanosome genes including bloodstream VSG genes, M
      VSG genes are expressed from promoters subject to exclusively transcriptional
      regulation in a life cycle stage-dependent manner. We have located an M-VSG gene
      promoter, and we demonstrate that it is specifically up-regulated at the
      metacyclic stage. This is the first demonstration of gene expression being
      regulated entirely at the level of transcription among the Kinetoplastida; all
      other protein-coding genes examined in these organisms are, at least partly,
      under posttranscriptional control. The distinctive mode of expression of M-VSG
      genes may be due to a stochastic mechanism for metacyclic VSG activation.

PMID- 7565748
TI  - Isolation of a gene encoding a functional zinc finger protein homologous to
      erythroid Kruppel-like factor: identification of a new multigene family.
AB  - We have identified and characterized the gene for a novel zinc finger
      transcription factor which we have termed lung Kruppel-like factor (LKLF). LKLF
      was isolated through the use of the zinc finger domain of erythroid Kruppel-like
      factor (ELKF) as a hybridization probe and is closely related to this erythroid
      cell-specific gene. LKLF is expressed in a limited number of tissues, with the
      predominant expression seen in the lungs and spleen. The gene is developmentally
      controlled, with expression noted in the 7-day embryo followed by a down
      regulation at 11 days and subsequent reactivation. A high degree of similarity is
      noted in the zinc finger regions of LKLF and EKLF. Beyond this domain, the
      sequences diverge significantly, although the putative transactivation domains
      for both LKLF and EKLF are proline-rich regions. In the DNA-binding domain, the
      three zinc finger motifs are so closely conserved that the predicted DNA contact
      sites are identical, suggesting that both proteins may bind to the same core
      sequence. This was further suggested by transactivation assays in which mouse
      fibroblasts were transiently transfected with a human beta-globin reporter gene
      in the absence and presence of an LKLF cDNA construct. Expression of the LKLF
      gene activates this human beta-globin promoter containing the CACCC sequence
      previously shown to be a binding site for EKLF. Mutation of this potential
      binding site results in a significant reduction in the reporter gene expression.
      LKLF and EKLF can thus be grouped as members of a unique family of transcription
      factors which have discrete patterns of expression in different tissues and which
      appear to recognize the same DNA-binding site.

PMID- 7565750
TI  - YY1 facilitates the association of serum response factor with the c-fos serum
      response element.
AB  - YY1 is a multifunctional transcription factor that acts as an activator or
      repressor in different contexts. YY1 binds to multiple sites in the mouse c-fos
      promoter, inducing at each site a sharp DNA bend. Binding of YY1 to a site
      situated between the cyclic AMP response element (CRE) and the TATA box bends the
      DNA in a way that interferes with the interaction of proteins bound at the CRE
      and TATA elements, resulting in repression of transcription. Here, we show that
      binding of YY1 to a different site in the c-fos promoter has a different result.
      Binding of YY1 to the c-fos serum response element (SRE) enhances the binding of
      serum response factor (SRF). This enhancement requires the binding of YY1 to SRE
      DNA. YY1 and SRF can cooccupy the SRE at least transiently. In the region of
      overlapping contact, YY1 contacts DNA in the major groove, while SRF contacts DNA
      in the minor groove. YY1 also enhances the association of SRF with the SRE in
      transfected insect cells. Thus, although YY1 induces similar structural changes
      in DNA at different binding sites, it can have distinct local effects on protein
      DNA and protein-protein interactions. These data support a general role for YY1
      in the building of highly organized promoter complexes.

PMID- 7565751
TI  - 3'-end-forming signals of yeast mRNA.
AB  - It was previously shown that three distinct but interdependent elements are
      required for 3' end formation of mRNA in the yeast Saccharomyces cerevisiae: (i)
      the efficiency element TATATA and related sequences, which function by enhancing
      the efficiency of positioning elements; (ii) positioning elements, such as
      TTAAGAAC and AAGAA, which position the poly(A) site; and (iii) the actual site of
      polyadenylation. In this study, we have shown that several A-rich sequences,
      including the vertebrate poly(A) signal AATAAA, are also positioning elements.
      Saturated mutagenesis revealed that optimum sequences of the positioning element
      were AATAAA and AAAAAA and that this element can tolerate various extents of
      replacements. However, the GATAAA sequence was completely ineffective. The major
      cleavage sites determined in vitro corresponded to the major poly(A) sites
      observed in vivo. Our findings support the assumption that some components of the
      basic polyadenylation machinery could have been conserved among yeasts, plants,
      and mammals, although 3' end formation in yeasts is clearly distinct from that of
      higher eukaryotes.

PMID- 7565749
TI  - Casein kinase II phosphorylation site mutations in c-Myb affect DNA binding and
      transcriptional cooperativity with NF-M.
AB  - Phosphorylation of c-Myb has been implicated in the regulation of the binding of
      c-Myb to DNA. We show that murine c-Myb is phosphorylated at Ser-11 and -12 in
      vivo and that these sites can be phosphorylated in vitro by casein kinase II
      (CKII), analogous to chicken c-Myb. An efficient method to study DNA binding
      properties of full-length c-Myb and Myb mutants under nondenaturing conditions
      was developed. It was found that a Myb mutant in which Ser-11 and -12 were
      replaced with Ala (Myb Ala-11/12), wild-type c-Myb, and Myb Asp-11/12 bound to
      the A site of the mim-1 promoter with decreasing affinities. In agreement with
      this finding, Myb Ala-11/12 transactivated better than wild-type c-Myb and Myb
      Asp-11/12 on the mim-1 promoter or a synthetic Myb-responsive promoter. Similar
      observations were made for the myeloid-specific neutrophil elastase promoter. The
      presence of NF-M or an NF-M-like activity abolished partially the differences
      seen with the Ser-11/12 mutants, suggesting that the reduced DNA binding due to
      negative charge at positions 11 and 12 can be compensated for by NF-M. Since no
      direct interaction of c-Myb and NF-M was observed, we propose that the
      cooperativity is mediated by a third factor. Our data offer two possibilities for
      how casein kinase II phosphorylation can influence c-Myb function: first, by
      reducing c-Myb DNA binding and thereby influencing transactivation, and second,
      by enhancing the apparent cooperativity between c-Myb and NF-M or an NF-M-like
      activity.

PMID- 7565752
TI  - Transcription of the human beta enolase gene (ENO-3) is regulated by an intronic
      muscle-specific enhancer that binds myocyte-specific enhancer factor 2 proteins
      and ubiquitous G-rich-box binding factors.
AB  - To provide evidence for the cis-regulatory DNA sequences and trans-acting factors
      involved in the complex pattern of tissue- and stage-specific expression of the
      beta enolase gene, constructs containing fragments of the gene fused to the
      chloramphenicol acetyltransferase gene were used in transient-transfection assays
      of C2C12 myogenic cells. Deletion analysis revealed the presence of four major
      regions: two negative regions in the 5'-flanking sequence, a basal promoter
      region which directs expression at low levels in proliferating and differentiated
      muscle cells, and a positive region within the first intron that confers cell
      type-specific and differentiation-induced expression. This positive regulatory
      element is located in the 3'-proximal portion of the first intron (nucleotides
      +504 to +637) and acts as an enhancer irrespective of orientation and position
      from the homologous beta enolase promoter or the heterologous thymidine kinase
      promoter, conferring in both cases muscle-specific expression to the linked
      reporter gene. Deletion of a putative myocyte-specific enhancer factor 1 (MEF-1)
      binding site, containing a canonical E-box motif, had no effects on muscle
      specific transcription, indicating that this site is not required for the
      activity of the enhancer. Gel mobility shift assays, competition analysis, DNase
      I footprinting, and mutagenesis studies indicated that this element interacts
      through an A/T-rich box with a MEF-2 protein(s) and through a G-rich box with a
      novel ubiquitous factor(s). Mutation of either the G-rich box or the A/T-rich box
      resulted in a significantly reduced activity of the enhancer in transient
      transfection assays. These data indicate that MEF-2 and G-rich-box binding
      factors are each necessary for tissue-specific expression of the beta enolase
      gene in skeletal muscle cells.

PMID- 7565754
TI  - Role of chromatin and Xenopus laevis heat shock transcription factor in
      regulation of transcription from the X. laevis hsp70 promoter in vivo.
AB  - Xenopus laevis oocytes activate transcription from the Xenopus hsp70 promoter
      within a chromatin template in response to heat shock. Expression of exogenous
      Xenopus heat shock transcription factor 1 (XHSF1) causes the activation of the
      wild-type hsp70 promoter within chromatin. XHSF1 activates transcription at
      normal growth temperatures (18 degrees C), but heat shock (34 degrees C)
      facilitates transcriptional activation. Titration of chromatin in vivo leads to
      constitutive transcription from the wild-type hsp70 promoter. The Y box elements
      within the hsp70 promoter facilitate transcription in the presence or absence of
      chromatin. The presence of the Y box elements prevents the assembly of canonical
      nucleosomal arrays over the promoter and facilitates transcription. In a mutant
      hsp70 promoter lacking Y boxes, exogenous XHSF1 activates transcription from a
      chromatin template much more efficiently under heat shock conditions. Activation
      of transcription from the mutant promoter by exogenous XHSF1 correlates with the
      disappearance of a canonical nucleosomal array over the promoter. Chromatin
      structure on a mutant hsp70 promoter lacking Y boxes can restrict XHSF1 access;
      however, on both mutant and wild-type promoters, chromatin assembly can also
      restrict the function of the basal transcriptional machinery. We suggest that
      chromatin assembly has a physiological role in establishing a transcriptionally
      repressed state on the Xenopus hsp70 promoter in vivo.

PMID- 7565753
TI  - Involvement of an AP-1 complex in zone-specific expression of the CYP11B1 gene in
      the rat adrenal cortex.
AB  - The CYP11B1 gene, which encodes steroid 11 beta-monooxygenase, which is
      responsible for the synthesis of cortisol and corticosterone, the major
      glucocorticoids in mammals, is expressed specifically in the zona fasciculata of
      the adrenal cortex. We have analyzed the promoter region of the rat CYP11B1 gene
      by using a transient-expression system with adrenocortical Y1 cells and have
      identified a positive regulatory region. The region contained two adjacent sites
      for the binding of Y1-cell nuclear proteins: the binding site for an AP-1
      transcription factor composed of JunD and a Fos-related protein, and the site for
      Ad4-binding protein (Ad4BP). The binding of the AP-1 factor to the regulatory
      region had a suppressive effect on that of Ad4BP in the nuclear extracts.
      Mutational analyses revealed that the transcriptional activation of the CYP11B1
      gene promoter in Y1 cells was attributable to the AP-1 site but not to the Ad4
      site. Subsequently, nuclear extracts of the zona fasciculata cells from the rat
      adrenal cortex were found to contain both AP-1 factor and Ad4BP, whose binding
      properties to the regulatory region were almost identical to those of the two
      factors in the Y1-cell nuclear extracts. Moreover, immunohistochemical analyses
      of rat adrenal cortices showed that the AP-1 factor was present in the nuclei of
      CYP11B1-expressing cells in the zona fasciculata but not in the nuclei of cells
      in the other zones. From these results, we propose that the AP-1 transcription
      factor found in this study plays an important role in the zone-specific
      expression of the CYP11B1 gene in rat adrenal cortex.

PMID- 7565755
TI  - Sug1 modulates yeast transcription activation by Cdc68.
AB  - The Cdc68 protein is required for the transcription of a variety of genes in the
      yeast Saccharomyces cerevisiae. In a search for proteins involved in the activity
      of the Cdc68 protein, we identified four suppressor genes in which mutations
      reverse the temperature sensitivity caused by the cdc68-1 allele. We report here
      the molecular characterization of mutations in one suppressor gene, the
      previously identified SUG1 gene. The Sug1 protein has been implicated in both
      transcriptional regulation and proteolysis. sug1 suppressor alleles reversed most
      aspects of the cdc68-1 mutant phenotype but did not suppress the lethality of a
      cdc68 null allele, indicating that sug1 suppression is by restoration of Cdc68
      activity. Our evidence suggests that suppression by sug1 is unlikely to be due to
      increased stability of mutant Cdc68 protein, despite the observation that Sug1
      affected proteolysis of mutant Cdc68. We report here that attenuated Sug1
      activity strengthens mutant Cdc68 activity, whereas increased Sug1 activity
      further inhibits enfeebled Cdc68 activity, suggesting that Sug1 antagonizes the
      activator function of Cdc68 for transcription. Consistent with this hypothesis,
      we find that Sug1 represses transcription in vivo.

PMID- 7565757
TI  - Cytokines inhibit p53-mediated apoptosis but not p53-mediated G1 arrest.
AB  - Murine erythroleukemia cells that lack endogenous p53 expression were transfected
      with a temperature-sensitive p53 allele. The temperature-sensitive p53 protein
      behaves as a mutant polypeptide at 37 degrees C and as a wild-type polypeptide at
      32 degrees C. Three independent clones expressing the temperature-sensitive p53
      protein were characterized with respect to p53-mediated G1 cell cycle arrest,
      apoptosis, and differentiation. Clone ts5.203 responded to p53 activation at 32
      degrees C by undergoing G1 arrest, apoptosis, and differentiation. Apoptosis was
      seen in cells representative of all phases of the cell cycle and was not
      restricted to cells arrested in G1. The addition of a cytokine (erythropoietin, c
      kit ligand, or interleukin-3) to the culture medium of ts5.203 cells blocked p53
      mediated apoptosis and differentiation but not p53-mediated G1 arrest. These
      observations indicate that apoptosis and G1 arrest can be effectively uncoupled
      through the action of cytokines acting as survival factors and are consistent
      with the idea that apoptosis and G1 arrest represent separate functions of p53.
      Clones ts15.15 and tsCB3.4 responded to p53 activation at 32 degrees C by
      undergoing G1 arrest but not apoptosis. We demonstrate that tsCB3.4 secretes a
      factor with erythropoietin-like activity and that ts15.15 secretes a factor with
      interleukin-3 activity and suggest that autocrine secretion of these cytokines
      blocks p53-mediated apoptosis. These data provide a framework in which to
      understand the variable responses of cells to p53 overexpression.

PMID- 7565756
TI  - Helix-loop-helix transcription factors mediate activation and repression of the
      p75LNGFR gene.
AB  - Sequence analysis of rat and human low-affinity nerve growth factor receptor
      p75LNGFR gene promoter regions revealed a single E-box cis-acting element,
      located upstream of the major transcription start sites. Deletion analysis of the
      E-box sequence demonstrated that it significantly contributes to p75LNGFR
      promoter activity. This E box has a dual function; it mediates either activation
      or repression of the p75LNGFR promoter activity, depending on the interacting
      transcription factors. We showed that the two isoforms of the class A basic helix
      loop-helix (bHLH) transcription factor ME1 (ME1a and ME1b), the murine homolog of
      the human HEB transcription factor, specifically repress p75LNGFR promoter
      activity. This repression can be released by coexpression of the HLH Id2
      transcriptional regulator. In vitro analyses demonstrated that ME1a forms a
      stable complex with the p75LNGFR E box and likely competes with activating E-box
      binding proteins. By using ME1a-overexpressing PC12 cells, we showed that the
      endogenous p75LNGFR gene is a target of ME1a repression. Together, these data
      demonstrate that the p75LNGFR E box and the interacting bHLH transcription
      factors are involved in the regulation of p75LNGFR gene expression. These results
      also show that class A bHLH transcription factors can repress and Id-like
      negative regulators can stimulate gene expression.

PMID- 7565758
TI  - Molecular cloning and characterization of NF-IL3A, a transcriptional activator of
      the human interleukin-3 promoter.
AB  - To isolate transcription factors important in the regulation of the human
      interleukin-3 (IL-3) gene, we screened a lambda gt11 cDNA library, constructed
      from phytohemagglutinin-stimulated human T-cell RNA, with a probe containing
      regulatory sequences in the upstream region of the IL-3 gene (located from bp 
      165 to -128 and referred to as the DNase I footprint A region). We isolated a
      0.96-kb cDNA that encoded a basic amino acid domain and a leucine zipper domain
      and used the "rapid amplification and cloning of 3' ends" technique to isolate
      the 3' half of the cDNA clone, generating a 1.9-kb full-length cDNA clone. Using
      in vitro-translated protein, which we call NF-IL3A, we defined the IL-3 promoter
      sequences bound by NF-IL3A in DNase I footprinting assays as TAATTACGTCTG and,
      using gel shift assays, defined ATTACG as the minimal sequence required for
      binding of NF-IL3A in vitro. Proteins that bind to the NF-IL3A binding site are
      found in both unstimulated and stimulated T-cell lines in similar amounts,
      although the level of NF-IL3A mRNA increases after T-cell activation in several
      mature T-cell lines. The NF-IL3A protein is nearly identical to a recently
      identified transcriptional repressor protein, E4BP4, and NF-IL3A binds
      specifically to regulatory sequences in both the adenovirus E4 promoter and the
      human gamma interferon promoter. Cotransfection experiments demonstrate that
      introduction of an expression vector containing the NF-IL3A cDNA into resting T
      cells transactivates IL-3 promoter-chloramphenicol acetyltransferase gene
      plasmids that contain the A region; this effect requires the presence of an
      intact NF-IL3A binding site. One or more copies of the A region also confer NF
      IL3A responsiveness on a heterologous promoter in T cells. NF-IL3A appears to
      play an important role in the expression of IL-3 by T cells.

PMID- 7565759
TI  - Regulation of chromosome segregation by Glc8p, a structural homolog of mammalian
      inhibitor 2 that functions as both an activator and an inhibitor of yeast protein
      phosphatase 1.
AB  - The Ipl1 protein kinase is essential for proper chromosome segregation and cell
      viability in the budding yeast Saccharomyces cerevisiae. We have previously shown
      that the temperature-sensitive growth phenotype of conditional ipl1-1ts mutants
      can be suppressed by a partial loss-of-function mutation in the GLC7 gene, which
      encodes the catalytic subunit (PP1C) of protein phosphatase 1, thus suggesting
      that this enzyme acts in opposition to the Ipl1 protein kinase in regulating
      yeast chromosome segregation. We report here that the Glc8 protein, which is
      related in primary sequence to mammalian inhibitor 2, also participates in this
      regulation. Like inhibitor 2, the Glc8 protein is heat stable, exhibits anomalous
      electrophoretic mobility, and functions in vitro as an inhibitor of yeast as well
      as rabbit skeletal muscle PP1C. Interestingly, overexpression as well as deletion
      of the GLC8 gene results in a partial suppression of the temperature-sensitive
      growth phenotype of ipl1ts mutants and also moderately reduces the amount of
      protein phosphatase 1 activity which is assayable in crude yeast lysates. In
      addition, the chromosome missegregation phenotype caused by an increase in the
      dosage of GLC7 is totally suppressed by the glc8-delta 101::LEU2 deletion
      mutation. These findings together suggest that the Glc8 protein is involved in
      vivo in the activation of PP1C and that when the Glc8 protein is overproduced, it
      may also inhibit PP1C function. Furthermore, site-directed mutagenesis studies of
      GLC8 suggest that Thr-118 of the Glc8 protein, which is equivalent to Thr-72 of
      inhibitor 2, may play a central role in the ability of this protein to activate
      and/or inhibit PP1C in vivo.

PMID- 7565760
TI  - Overexpression of the zinc finger protein MZF1 inhibits hematopoietic development
      from embryonic stem cells: correlation with negative regulation of CD34 and c-myb
      promoter activity.
AB  - Zinc finger genes encode proteins that act as transcription factors. The myeloid
      zinc finger 1 (MZF1) gene encodes a zinc finger protein with two DNA-binding
      domains that recognize two distinct consensus sequences, is preferentially
      expressed in hematopoietic cells, and may be involved in the transcriptional
      regulation of hematopoiesis-specific genes. Reverse transcription-PCR analysis of
      human peripheral blood CD34+ cells cultured under lineage-restricted conditions
      demonstrated MZF1 expression during both myeloid and erythroid differentiation.
      Sequence analysis of the 5'-flanking region of the CD34 and c-myb genes, which
      are a marker of and a transcriptional factor required for hematopoietic
      proliferation and differentiation, respectively, revealed closely spaced MZF1
      consensus binding sites found by electrophoretic mobility shift assays to
      interact with recombinant MZF1 protein. Transient or constitutive MZF1 expression
      in different cell types resulted in specific inhibition of chloramphenicol
      acetyltransferase activity driven by the CD34 or c-myb 5'-flanking region. To
      determine whether transcriptional modulation by MZF1 activity plays a role in
      hematopoietic differentiation, constructs containing the MZF1 cDNA under the
      control of different promoters were transfected into murine embryonic stem cells
      which, under defined in vitro culture conditions, generate colonies of multiple
      hematopoietic lineages. Constitutive MZF1 expression interfered with the ability
      of embryonic stem cells to undergo hematopoietic commitment and erythromyeloid
      colony formation and prevented the induced expression of CD34 and c-myb mRNAs
      during differentiation of these cells. These data indicate that MZF1 plays a
      critical role in hematopoiesis by modulating the expression of genes involved in
      this process.

PMID- 7565761
TI  - Nuclear localization of v-Abl leads to complex formation with cyclic AMP response
      element (CRE)-binding protein and transactivation through CRE motifs.
AB  - Deregulated expression of v-abl and BCR/abl genes has been associated with
      myeloproliferative syndromes and myelodysplasia, both of which can progress to
      acute leukemia. These studies identify the localization of the oncogenic form of
      the abl gene product encoded by the Abelson murine leukemia virus in the nuclei
      of myeloid cells and the association of the v-Abl protein with the
      transcriptional regulator cyclic AMP response element-binding protein (CREB). We
      have mapped the specific domains within each of the proteins responsible for this
      interaction. We have shown that complex formation is a prerequisite for
      transcriptional potentiation of CREB. Transient overexpression of the homologous
      cellular protein c-Abl also results in the activation of promoters containing an
      intact CRE. These observations identify a novel function for v-Abl, that of a
      transcriptional activator that physically interacts with a transcription factor.

PMID- 7565762
TI  - 12-O-tetradecanoylphorbol-13-acetate activation of the MDR1 promoter is mediated
      by EGR1.
AB  - P-glycoprotein, the product of the MDR1 gene (multidrug resistance gene 1), is an
      energy-dependent efflux pump associated with treatment failure in some
      hematopoietic malignancies. Its expression is regulated during normal
      hematopoietic differentiation, although its function in normal hematopoietic
      cells is unknown. To identify cellular factors that regulate the expression of
      MDR1 in hematopoietic cells, we characterized the cis- and trans-acting factors
      mediating 12-O-tetradecanoylphorbol-13-acetate (TPA) activation of the MDR1
      promoter in K562 cells. Transient-transfection assays demonstrated that an MDR1
      promoter construct containing nucleotides -69 to +20 conferred a TPA response
      equal to that of a construct containing nucleotides -434 to +105. TPA induced
      EGR1 binding to the -69/+20 promoter sequences over a time course which
      correlated with increased MDR1 promoter activity and increased steady-state MDR1
      RNA levels. The -69/+20 promoter region contains an overlapping SP1/EGR site. The
      TPA-responsive element was localized to the overlapping SP1/EGR site by using a
      synthetic reporter construct. A mutation in this site that inhibited EGR protein
      binding blocked the -69/+20 MDR1 promoter response to TPA. The expression of a
      dominant negative EGR protein also blocked the TPA response of the -69/+20
      promoter construct. Finally, the expression of EGR1 was sufficient to activate a
      construct containing tandem MDR1 promoter SP1/EGR sites. These data suggest a
      role for EGR1 in modulating MDR1 promoter activity in hematopoietic cells.

PMID- 7565763
TI  - Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in
      Saccharomyces cerevisiae.
AB  - Rox1 is a repressor of the hypoxic genes of Saccharomyces cerevisiae. It binds to
      a specific hypoxic consensus sequence in the upstream region of these genes and
      represses transcription in conjunction with the general repression complex Tup1
      Ssn6. In this study, we demonstrated that the first 100 amino acids comprising
      the HMG domain of Rox1 were responsible for DNA binding and that when bound, Rox1
      bent DNA at an angle of 90 degrees. A mutational analysis resulted in the
      isolation of seven missense mutations, all located within the HMG domain, that
      caused loss of DNA binding. The effect of these mutations on the structure of
      Rox1 was evaluated on the basis of the homology between Rox1 and the human male
      sex-determining protein SRY, for which a structural model is available. The
      failure to isolate missense mutations in the carboxy-terminal three-quarters of
      the protein prompted a deletion analysis of this region. The results suggested
      that this region was responsible for the repression function of Rox1 and that the
      repression information was redundant. This hypothesis was confirmed by using a
      set of fusions between sequences encoding the GAL4 DNA-binding domain and
      portions of ROX1. Those fusions containing either the entire carboxy-terminal
      region or either half of it were capable of repression. Repression by selected
      fusions was demonstrated to be dependent on Ssn6.

PMID- 7565764
TI  - The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on
      chromosome 3 whose product has a potential coiled-coil domain.
AB  - Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one
      of the receptors for the nerve growth factor, are frequently detected in thyroid
      carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end
      sequences belonging to different genes. In previously reported studies we have
      demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR,
      both localized similarly to the receptor tyrosine kinase, on the q arm of
      chromosome 1. Here we report the characterization of a novel NTRK1-derived
      thyroid oncogene, named TRK-T3. A cDNA clone, capable of transforming activity,
      was isolated from a transformant cell line. Sequence analysis revealed that TRK
      T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to a
      novel gene that we have named TFG (TRK-fused gene). The TRK-T3 amino acid
      sequence displays, within the TFG region, a coiled-coil motif that could endow
      the oncoprotein with the capability to form complexes. The TRK-T3 oncogene
      encodes a 68-kDa cytoplasmic protein reacting with NTRK1-specific antibodies. By
      sedimentation gradient experiments the TRK-T3 oncoprotein was shown to form, in
      vivo, multimeric complexes, most likely trimers or tetramers. The TFG gene is
      ubiquitously expressed and is located on chromosome 3. The breakpoint producing
      the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene
      and produces a chimeric exon that undergoes alternative splicing. Molecular
      analysis of the NTRK1 rearranged fragments indicated that the chromosomal
      rearrangement is reciprocal and balanced and involves loss of a few nucleotides
      of germ line sequences.

PMID- 7565765
TI  - Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a
      specific signal for the RAD9 checkpoint.
AB  - A cdc13 temperature-sensitive mutant of Saccharomyces cerevisiae arrests in the
      G2 phase of the cell cycle at the restrictive temperature as a result of DNA
      damage that activates the RAD9 checkpoint. The DNA lesions present after a
      failure of Cdc13p function appear to be located almost exclusively in telomere
      proximal regions, on the basis of the profile of induced mitotic recombination.
      cdc13 rad9 cells dividing at the restrictive temperature contain single-stranded
      DNA corresponding to telomeric and telomere-proximal DNA sequences and eventually
      lose telomere-associated sequences. These results suggest that the CDC13 product
      functions in telomere metabolism, either in the replication of telomeric DNA or
      in protecting telomeres from the double-strand break repair system. Moreover,
      since cdc13 rad9 cells divide at a wild-type rate for several divisions at the
      restrictive temperature while cdc13 RAD9 cells arrest in G2, these results also
      suggest that single-stranded DNA may be a specific signal for the RAD9
      checkpoint.

PMID- 7565767
TI  - Transcriptional activation of the Epstein-Barr virus latency C promoter after 5
      azacytidine treatment: evidence that demethylation at a single CpG site is
      crucial.
AB  - The Epstein-Barr Virus (EBV) latency C promoter (Cp) is the origin of transcripts
      for six viral proteins. The promoter is active in lymphoblastoid B-cell lines but
      silent in many EBV-associated tumors and tumor cell lines. In these latter cell
      lines, the viral episome is hypermethylated in the vicinity of this promoter. We
      show that in such a cell line (Rael, a Burkitt's lymphoma line), 5-azacytidine
      inhibits DNA methyltransferase, brings about demethylation of EBV genomes,
      activates Cp transcription, and induces the expression of EBNA-2. Investigation
      of the phenomenon demonstrates the importance of the methylation status of a
      particular CpG site for the regulation of the Cp: (i) genomic sequencing shows
      that this site is methylated when the Cp is inactive and is not methylated when
      the promoter is active; (ii) methylation or transition mutation at this site
      abolishes complex formation with a cellular binding activity (CBF2) as determined
      by electrophoretic mobility shift analyses, competition binding analyses, and
      DNase I footprinting; and (iii) a single C --> T transition mutation at this site
      is associated with a marked reduction (> 50-fold) of transcriptional activity in
      a reporter plasmid. Thus, the CBF2 binding activity is shown to be methylation
      sensitive and crucial to EBNA-2-mediated activation of the Cp.

PMID- 7565766
TI  - Identification of a silencer module which selectively represses cyclic AMP
      responsive element-dependent gene expression.
AB  - The cyclic AMP (cAMP)-inducible promoter from the rat lactate dehydrogenase A
      subunit gene (LDH A) is associated with a distal negative regulatory element (LDH
      NRE) that represses inherent basal and cAMP-inducible promoter activity. The
      element is of dyad symmetry, consisting of a palindromic sequence with two half
      sites, 5'-TCTTG-3'. It represses the expression of an LDH A/chloramphenicol
      acetyltransferase (CAT) reporter gene in a dose-dependent, orientation- and
      position-independent fashion, suggesting that it is a true silencer element.
      Uniquely, it selectively represses cAMP-responsive element (CRE)-dependent
      transcription but has no effect on promoters lacking a CRE sequence. The
      repressing action of LDH-NRE could be overcome by cotransfection with LDH A/CAT
      vector oligonucleotides containing either the LDH-NRE or CRE sequence. This
      suggests that the reversal of repression was caused by the removal of functional
      active, limiting transacting factors which associate with LDH-NRE as well as with
      CRE. Gel mobility shift, footprinting, and Southwestern blotting assays
      demonstrated the presence of a 69-kDa protein with specific binding activity for
      LDH-NRE. Additionally, gel supershift assays with anti-CREB and anti-Fos
      antibodies indicate the presence of CREB and Fos or antigenically closely related
      proteins with the LDH-NRE/protein complex. We suggest that the LDH-NRE and CRE
      modules functionally interact to achieve negative modulation of cAMP-responsive
      LDH A transcriptional activity.

PMID- 7565768
TI  - Angiotensin II stimulates calcium-dependent activation of c-Jun N-terminal
      kinase.
AB  - In GN4 rat liver epithelial cells, angiotensin II (Ang II) and other agonists
      which activate phospholipase C stimulate tyrosine kinase activity in a calcium
      dependent, protein kinase C (PKC)-independent manner. Since Ang II also produces
      a proliferative response in these cells, we investigated downstream signaling
      elements traditionally linked to growth control by tyrosine kinases. First, Ang
      II, like epidermal growth factor (EGF), stimulated AP-1 binding activity in a PKC
      independent manner. Because increases in AP-1 can reflect induction of c-Jun and
      c-Fos, we examined the activity of the mitogen-activated protein (MAP) kinase
      family members Erk-1 and -2 and the c-Jun N-terminal kinase (JNK), which are
      known to influence c-Jun and c-Fos transcription. Ang II stimulated MAP kinase
      (MAPK) activity but only approximately 50% as effectively as EGF; again, these
      effects were independent of PKC. Ang II also produced a 50- to 200-fold
      activation of JNK in a PKC-independent manner. Unlike its smaller effect on MAPK,
      Ang II was approximately four- to sixfold more potent in activating JNK than EGF
      was. Although others had reported a lack of calcium ionophore-stimulated JNK
      activity in lymphocytes and several other cell lines, we examined the role of
      calcium in GN4 cells. The following results suggest that JNK activation in rat
      liver epithelial cells is at least partially Ca(2+) dependent: (i) norepinephrine
      and vasopressin hormones that increase inositol 1,4,5-triphosphate stimulated
      JNK; (ii) both thapsigargin, a compound that produces an intracellular Ca(2+)
      signal, and Ca(2+) ionophores stimulated a dramatic increase in JNK activity (up
      to 200-fold); (iii) extracellular Ca(2+) chelation with ethylene glycol
      tetraacetic acid (EGTA) inhibited JNK activation by ionophore and intracellular
      chelation with 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid
      tetraacetoxymethyl-ester (BAPTA-AM) partially inhibited JNK activation by Ang II
      or thapsigargin; and (iv) JNK activation by Ang II was inhibited by pretreatment
      of cells with thapsigargin and EGTA, a procedure which depletes intracellular
      Ca(2+) stores. JNK activation following Ang II stimulation did not involve
      calmodulin; either W-7 nor calmidizolium, in concentrations sufficient to inhibit
      Ca(2+)/calmodulin-dependent kinase II, blocked JNK activation by Ang II. In
      contrast, genistein, in concentrations sufficient to inhibit Ca(2+)-dependent
      tyrosine phosphorylation, prevented Ang II and thapsigargin-induced JNK
      activation. In summary, in GN4 rat liver epithelial cells, Ang II stimulates JNK
      via a novel Ca(2+)-dependent pathway. The inhibition by genistein suggest that
      Ca(2+)-dependent tyrosine phosphorylation may modulate the JNK pathway in a cell
      type-specific manner, particularly in cells with a readily detectable Ca(2+)
      regulated tyrosine kinase.

PMID- 7565769
TI  - The POU homeodomain transcription factor Oct-1 is essential for activity of the
      gonadotropin-releasing hormone neuron-specific enhancer.
AB  - The mechanisms of specification of gene expression in a complex tissue such as
      the brain remain poorly understood. To provide a model system for the study of
      gene regulation in a specific subpopulation of differentiated neurons, we have
      derived cell lines from tumors created in transgenic mice by targeting simian
      virus 40 T antigen expression by using the regulatory regions of the gene for
      gonadotropin-releasing hormone (GnRH), a decapeptide released from specialized
      neurons in the hypothalamus. Transfections into the cultured GnRH-secreting
      hypothalamic neuronal cell line GT1 have identified a neuron-specific enhancer,
      1.5 kb upstream of the GnRH gene, which binds multiple GT1 nuclear proteins. In
      particular, one AT-rich protein-binding region, AT-a, is critical for enhancer
      activity. In this study, we used electrophoretic mobility shift assays to detect
      a GT1 nuclear protein complex that binds the AT-a region. Close inspection of the
      AT-a bottom-strand sequence revealed homology to the octamer motif, a sequence
      known to bind members of the POU homeodomain transcription factor family.
      Although we demonstrate expression of a number of POU homeodomain genes in GT1
      cells, a supershift assay with Oct-1 antibody demonstrates that Oct-1 is the
      protein binding the enhancer. Finally, specific mutations in the AT-a region that
      affected Oct-1 binding were correlated with decreased transcription. Thus, Oct-1
      binds to the GnRH enhancer in vitro, and this binding is critical to the
      transcriptional activity of this neuron-specific enhancer in GT1 cells.

PMID- 7565771
TI  - Functional coupling of a mammalian somatostatin receptor to the yeast pheromone
      response pathway.
AB  - A detailed analysis of structural and functional aspects of G-protein-coupled
      receptors, as well as discovery of novel pharmacophores that exert their effects
      on members of this class of receptors, will be facilitated by development of a
      yeast-based bioassay. To that end, yeast strains that functionally express the
      rat somatostatin receptor subtype 2 (SSTR2) were constructed. High-affinity
      binding sites for somatostatin ([125I-Tyr-11]S-14) comparable to those in native
      tissues were detected in yeast membrane extracts at levels equivalent to the
      alpha-mating pheromone receptor (Ste2p). Somatostatin-dependent growth of strains
      modified by deletion of genes encoding components of the pheromone response
      pathway was detected through induction of a pheromone-responsive HIS3 reporter
      gene, enabling cells to grow on medium lacking histidine. Dose-dependent growth
      responses to S-14 and related SSTR2 subtype-selective agonists that were
      proportional to the affinity of the ligands for SSTR2 were observed. The growth
      response required SSTR2, G alpha proteins, and an intact signal transduction
      pathway. The sensitivity of the bioassay was affected by intracellular levels of
      the G alpha protein. A mutation in the SST2 gene, which confers supersensitivity
      to pheromone, was found to significantly enhance the growth response to S-14. In
      sst2 delta cells, SSTR2 functionally interacted with both a chimeric
      yeast/mammalian G alpha protein and the yeast G alpha protein, Gpa1p; to promote
      growth. These yeast strains should serve as a useful in vivo reconstitution
      system for examination of molecular interactions of the G-protein-coupled
      receptors and G proteins.

PMID- 7565770
TI  - Stimulation of transcription factor binding and histone displacement by
      nucleosome assembly protein 1 and nucleoplasmin requires disruption of the
      histone octamer.
AB  - To investigate the mechanisms by which transcription factors invade nucleosomal
      DNA and replace histones at control elements, we have examined the response of
      the histone octamer to transcription factor binding in the presence of histone
      binding proteins (i.e., nucleosome assembly factors). We found that yeast
      nucleosome assembly protein 1 (NAP-1) stimulated transcription factor binding and
      nucleosome displacement in a manner similar to that of nucleoplasmin. In
      addition, disruption of the histone octamer was required both for the stimulation
      of transcription factor binding to nucleosomal DNA and for transcription factor
      induced nucleosome displacement mediated by nucleoplasmin or NAP-1. While NAP-1
      and nucleoplasmin stimulated the binding of a fusion protein (GAL4-AH) to control
      nucleosome cores, this stimulation was lost upon covalent histone-histone cross
      linking within the histone octamers. In addition, both NAP-1 and nucleoplasmin
      were able to mediate histone displacement upon the binding of five GAL4-AH dimers
      to control nucleosome cores; however, this activity was also forfeited when the
      histone octamers were cross-linked. These data indicate that octamer disruption
      is required for both stimulation of factor binding and factor-dependent histone
      displacement by nucleoplasmin and NAP-1. By contrast, transcription factor
      induced histone transfer onto nonspecific competitor DNA did not require
      disruption of the histone octamer. Thus, histone displacement in this instance
      occurred by transfer of complete histone octamers, a mechanism distinct from that
      mediated by the histone-binding proteins nucleoplasmin and NAP-1.

PMID- 7565772
TI  - The mitochondrial receptor complex: the small subunit Mom8b/Isp6 supports
      association of receptors with the general insertion pore and transfer of
      preproteins.
AB  - The mitochondrial outer membrane contains import receptors for preproteins and a
      multisubunit general insertion pore. Several small outer membrane proteins (< 10
      kDa) have been identified by their association with receptors or the general
      insertion pore, yet little is known about their function. Here, we present
      evidence that the biochemically identified Mom8b and the genetically identified
      Isp6 are identical. A deletion of Mom8b/Isp6 in Saccharomyces cerevisiae leads to
      (i) a delay of import of preproteins, (ii) stabilization of preprotein binding to
      receptors and the general insertion pore, and (iii) destabilization of the
      interaction between receptors and the general insertion pore. These results
      suggest that Mom8b supports the cooperativity between receptors and the general
      insertion pore and facilitates the release of preproteins from import components
      and thereby promotes efficient transfer of preproteins.

PMID- 7565773
TI  - A light-induced protease from barley plastids degrades NADPH:protochlorophyllide
      oxidoreductase complexed with chlorophyllide.
AB  - The NADPH:protochlorophyllide oxidoreductase precursor protein (pPorA) of barley
      (Hordeum vulgare L. cv. Carina), synthesized from a full-length cDNA clone by
      coupling in vitro transcription and translation, is a catalytically active
      protein. It converts protochlorophyllide to chlorophyllide in a light- and NADPH
      dependent manner. At least the pigment product of catalysis remains tightly bound
      to the precursor protein. The chlorophyllide-pPorA complex differs markedly from
      the protochlorophyllide-pPorA complex with respect to sensitivity to attack by a
      light-induced, nucleus-encoded, and energy-dependent protease activity of barley
      plastids. The pPorA-chlorophyllide complex is rapidly degraded, in contrast to
      pPorA-protochlorophyllide complexes containing or lacking NADPH, which are both
      resistant to protease treatment. Unexpectedly, pPorA devoid of its substrates or
      products was less sensitive to proteolysis than the pPorA-chlorophyllide complex,
      suggesting that both substrate binding and product formation during catalysis had
      caused differential changes in protein conformation.

PMID- 7565774
TI  - Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton
      protein with a structurally conserved putative zinc finger domain.
AB  - The activation of growth factor receptor tyrosine kinases leads to tyrosine
      phosphorylation of many intracellular proteins which are thought to play crucial
      roles in growth factor signaling pathways. We previously showed that tyrosine
      phosphorylation of a 115-kDa protein is rapidly induced in cells treated with
      hepatocyte growth factor. To clarify the structure and possible function of the
      115-kDa protein (designated Hrs for hepatocyte growth factor-regulated tyrosine
      kinase substrate), we purified this protein from B16-F1 mouse melanoma cells by
      anti-phosphotyrosine immunoaffinity chromatography and determined its partial
      amino acid sequences. On the basis of the amino acid sequences, we molecularly
      cloned the cDNA for mouse Hrs. The nucleotide sequence of the cDNA revealed that
      Hrs is a novel 775-amino-acid protein with a putative zinc finger domain that is
      structurally conserved in several other proteins. This protein also contained a
      proline-rich region and a proline- and glutamine-rich region. The expression of
      Hrs mRNA was detected in all adult mouse tissues tested and also in embryos. To
      analyze the Hrs cDNA product, we prepared a polyclonal antibody against
      bacterially expressed Hrs. Using this antibody, we showed by subcellular
      fractionation that Hrs is localized to the cytoplasm; we also showed that that
      tyrosine phosphorylation of Hrs is induced in cells treated with epidermal growth
      factor or platelet-derived growth factor. These results suggest that Hrs plays a
      unique and important role in the signaling pathway of growth factors.

PMID- 7565775
TI  - Mutational analysis of mRNA capping enzyme identifies amino acids involved in GTP
      binding, enzyme-guanylate formation, and GMP transfer to RNA.
AB  - Vaccinia virus mRNA capping enzyme is a multifunctional protein with RNA
      triphosphatase, RNA guanylyltransferase, RNA (guanine-7) methyltransferase, and
      transcription termination factor activities. The protein is a heterodimer of 95-
      and 33-kDa subunits encoded by the vaccinia virus D1 and D12 genes, respectively.
      The capping reaction entails transfer of GMP from GTP to the 5'-diphosphate end
      of mRNA via a covalent enzyme-(lysyl-GMP) intermediate. The active site is
      situated at Lys-260 of the D1 subunit within a sequence element, KxDG (motif I),
      that is conserved in the capping enzymes from yeasts and other DNA viruses and at
      the active sites of covalent adenylylation of RNA and DNA ligases. Four
      additional sequence motifs (II to V) are conserved in the same order and with
      similar spacing among the capping enzymes and several ATP-dependent ligases. The
      relevance of these common sequence elements to the RNA capping reaction was
      addressed by mutational analysis of the vaccinia virus D1 protein. Nine alanine
      substitution mutations were targeted to motifs II to V. Histidine-tagged versions
      of the mutated D1 polypeptide were coexpressed in bacteria with the D12 subunit,
      and the His-tagged heterodimers were purified by Ni affinity and phosphocellulose
      chromatography steps. Whereas each of the mutated enzymes retained
      triphosphatase, methyltransferase, and termination factor activities, six of nine
      mutant enzymes were defective in some aspect of transguanylylation. Individual
      mutations in motifs III, IV, and V had distinctive effects on the affinity of
      enzyme for GTP, the rate of covalent catalysis (EpG formation), or the transfer
      of GMP from enzyme to RNA. These results are concordant with mutational studies
      of yeast RNA capping enzyme and suggest a conserved structural basis for covalent
      nucleotidyl transfer.

PMID- 7565777
TI  - Adenovirus type 12-induced fragility of the human RNU2 locus requires U2 small
      nuclear RNA transcriptional regulatory elements.
AB  - Infection of human cells with oncogenic adenovirus type 12 (Ad12) induces four
      specific chromosome fragile sites. Remarkably, three of these sites appear to
      colocalize with tandem arrays of genes encoding small, abundant, ubiquitously
      expressed structural RNAs--the RNU1 locus encoding U1 small nuclear RNA (snRNA),
      the RNU2 locus encoding U2 snRNA, and the RN5S locus encoding 5S rRNA. Recently,
      an artificial tandem array of the natural 5.8-kb U2 repeat unit has been shown to
      generate a new Ad12-inducible fragile site (Y.-P. Li, R. Tomanin, J. R. Smiley,
      and S. Bacchetti, Mol. Cell. Biol. 13:6064-6070, 1993), demonstrating that the U2
      repeat unit alone is sufficient for virally induced fragility. To identify
      elements within the U2 repeat unit that are required for virally induced
      fragility, we generated cell lines containing artificial tandem arrays of the
      entire 5.8-kb repeat unit, an 834-bp fragment spanning the U2 gene alone, or the
      same 834-bp fragment from which key U2 transcriptional regulatory elements had
      been deleted. The U2 snRNA coding regions within each artificial array were
      marked by an innocuous single base change (U to C at position 87) so that the
      relative expression of supernumerary and endogenous U2 genes could be monitored
      by a primer extension assay. We find that artificial arrays of both the 5.8- and
      the 0.8-kb U2 repeat units are fragile but that arrays lacking either the distal
      sequence element or both the distal and the proximal sequence elements of the
      promoter are not. Surprisingly, variations in repeat copy number and/or
      transcriptional activity of the artificial arrays do not appear to correlate with
      the degree of Ad12-inducible fragility. We conclude that U2 transcriptional
      regulatory elements are required for virally induced fragility but not
      necessarily U2 snRNA transcription per se.

PMID- 7565776
TI  - The Saccharomyces cerevisiae HSP12 gene is activated by the high-osmolarity
      glycerol pathway and negatively regulated by protein kinase A.
AB  - The HSP12 gene encodes one of the two major small heat shock proteins of
      Saccharomyces cerevisiae. Hsp12 accumulates massively in yeast cells exposed to
      heat shock, osmostress, oxidative stress, and high concentrations of alcohol as
      well as in early-stationary-phase cells. We have cloned an extended 5'-flanking
      region of the HSP12 gene in order to identify cis-acting elements involved in
      regulation of this highly expressed stress gene. A detailed analysis of the HSP12
      promoter region revealed that five repeats of the stress-responsive CCCCT motif
      (stress-responsive element [STRE]) are essential to confer wild-type induced
      levels on a reporter gene upon osmostress, heat shock, and entry into stationary
      phase. Disruption of the HOG1 and PBS2 genes leads to a dramatic decrease of the
      HSP12 inducibility in osmostressed cells, whereas overproduction of Hog1 produces
      a fivefold increase in wild-type induced levels upon a shift to a high salt
      concentration. On the other hand, mutations resulting in high protein kinase A
      (PKA) activity reduce or abolish the accumulation of the HSP12 mRNA in stressed
      cells. Conversely, mutants containing defective PKA catalytic subunits exhibit
      high basal levels of HSP12 mRNA. Taken together, these results suggest that HSP12
      is a target of the high-osmolarity glycerol (HOG) response pathway under negative
      control of the Ras-PKA pathway. Furthermore, they confirm earlier observations
      that STRE-like sequences are responsive to a broad range of stresses and that the
      HOG and Ras-PKA pathways have antagonistic effects upon CCCCT-driven
      transcription.

PMID- 7565778
TI  - The transcriptionally competent U2 gene is necessary and sufficient for
      adenovirus type 12 induction of the fragile site at 17q21-22.
AB  - Adenovirus type 12 induces four fragile sites upon infection of human cells. The
      U2 locus, consisting of up to 20 tandem repeats of a 5.8-kbp monomer, maps at the
      most sensitive of these sites at 17q21-22. We have previously shown that an
      artificial U2 locus integrated into the human genome generates a new virus
      induced fragile site. To determine which elements within the U2 monomer are
      responsible for fragility, we constructed loci consisting of tandem repeats of
      subfragments of the U2 monomer. With this approach, we demonstrate that a
      transcriptionally competent U2 gene is necessary and sufficient for virus-induced
      fragility and that no other element within the 5.8-kbp monomer contributes to
      this effect.

PMID- 7565779
TI  - Role of EGR-1 in thapsigargin-inducible apoptosis in the melanoma cell line A375
      C6.
AB  - Induction of apoptosis by diverse exogenous signals is dependent on elevation of
      intracellular Ca2+. This process of cell death can be blocked by actinomycin D,
      indicating that it requires gene transcription events. To identify genes that are
      required for apoptosis, we used thapsigargin (TG), which inhibits endoplasmic
      reticulum-dependent Ca(2+)-ATPase and thereby increases cytosolic Ca2+. Exposure
      to TG led to induction of the zinc finger transcription factor, EGR-1, and
      apoptosis in human melanoma cells, A375-C6. To determine the functional relevance
      of EGR-1 expression in TG-inducible apoptosis, we employed a dominant negative
      mutant which functionally competes with EGR-1 in these cells. Interestingly, the
      dominant negative mutant inhibited TG-inducible apoptosis. Consistent with this
      observation, an antisense oligomer directed against Egr-1 also led to a
      diminution of the number of cells that undergo TG-inducible apoptosis. These
      results suggest a novel regulatory role for EGR-1 in mediating apoptosis that is
      induced by intracellular Ca2+ elevation. We have previously shown that in these
      melanoma cells, EGR-1 acts to inhibit the growth arresting action of interleukin
      1. Together, these results imply that EGR-1 plays inducer-specific roles in
      growth control.

PMID- 7565782
TI  - Selection of novel exon recognition elements from a pool of random sequences.
AB  - A 20-nucleotide sequence close to the 3' end of the internal exon of a model two
      intron, three-exon pre-mRNA (DUP184 [Z. Dominski and R. Kole, J. Biol. Chem.
      269:23590-23596, 1994]) was replaced by a random 20-mer, resulting in a pool of
      pre-mRNAs which, like the initial DUP184 construct, were spliced in vitro by a
      pathway leading to predominant skipping of the internal exon. The randomized pre
      mRNAs were subjected to a selection protocol, resulting in a pool enriched in pre
      mRNAs that efficiently included the internal exon. Isolation and sequencing of a
      number of clones corresponding to the selected pre-mRNAs showed that two classes
      of sequences were selected from the initial pool. Most abundant among these were
      sequences with purine tracts similar to those in the recently identified exon
      splicing enhancers while a smaller class included sequences lacking discernible
      purine tracts within the 20-nucleotide region. Splicing of selected pre-mRNAs
      showed that the purine tracts vary in their ability to promote exon inclusion
      and, more important, that sequences lacking purine tracts stimulate inclusion of
      the internal exon as efficiently as their purine-rich counterparts. The latter
      result indicates the existence of a novel class of exon recognition sequences or
      splicing enhancers.

PMID- 7565781
TI  - Subregions of the adenovirus E1A transactivation domain target multiple
      components of the TFIID complex.
AB  - Transcriptional activation by the adenovirus E1A 289R protein requires direct
      contacts with the TATA box-binding protein (TBP) and also displays a critical
      requirement for TBP-associated factors (TAFs) (T.G. Boyer and A. J. Berk, Genes
      Dev. 7:1810-1823, 1993; J. V. Geisberg, W. S. Lee, A. J. Berk, and R. P.
      Ricciardi, Proc. Natl. Acad. Sci. USA 91:2488-2492, 1994; W. S. Lee, C. C. Kao,
      G. O. Bryant, X. Liu, and A. J. Berk, Cell 67:365-376, 1991; and Q. Zhou, P. M.
      Lieberman, T. G. Boyer, and A. J. Berk, Genes Dev. 6:1964-1974, 1992). In this
      report, we demonstrate that the activation domain of E1A (CR3) specifically binds
      to two TAFs, human TAFII250 (hTAFII250) and Drosophila TAFII110 (dTAFII110).
      These interactions can take place both in vivo and in vitro and require the
      carboxy-terminal region of CR3; the zinc finger region of CR3, which binds TBP,
      is not needed to bind these TAFs. We mapped the E1A-binding sites on hTAFII250 to
      an internal region that contains a number of structural motifs, including an HMG
      box, a bromodomain, and direct repeats. This represents the first demonstration
      that hTAFII250 may serve as a target of a transcriptional activator. We also
      mapped the E1A binding on dTAFII110 to its C-terminal region. This is of
      significance since, by contrast, Sp1-mediated activation requires binding to the
      N-terminal domain of dTAFII110. Thus, distinct surfaces of dTAFII110 can serve as
      target sites for different activators. Our results indicate that E1A may activate
      transcription, in part, through direct contacts of the CR3 subdomains with
      selected components of the TFIID complex.

PMID- 7565780
TI  - Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the
      Drosophila gene for an SR protein splicing factor.
AB  - SR proteins are essential for pre-mRNA splicing in vitro, act early in the
      splicing pathway, and can influence alternative splice site choice. Here we
      describe the isolation of both dominant and loss-of-function alleles of B52, the
      gene for a Drosophila SR protein. The allele B52ED was identified as a dominant
      second-site enhancer of white-apricot (wa), a retrotransposon insertion in the
      second intron of the eye pigmentation gene white with a complex RNA-processing
      defect. B52ED also exaggerates the mutant phenotype of a distinct white allele
      carrying a 5' splice site mutation (wDR18), and alters the pattern of sex
      specific splicing at doublesex under sensitized conditions, so that the male
      specific splice is favored. In addition to being a dominant enhancer of these RNA
      processing defects, B52ED is a recessive lethal allele that fails to complement
      other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which
      it was derived revealed a single change in a conserved amino acid in the beta 4
      strand of the first RNA-binding domain of B52, which suggests that altered RNA
      binding is responsible for the dominant phenotype. Reversion of the B52ED
      dominant allele with X rays led to the isolation of a B52 null allele. Together,
      these results indicate a critical role for the SR protein B52 in pre-mRNA
      splicing in vivo.

PMID- 7565783
TI  - Novel NFAT sites that mediate activation of the interleukin-2 promoter in
      response to T-cell receptor stimulation.
AB  - The transcription factors NFAT and AP-1 have been shown to be essential for
      inducible interleukin-2 (IL-2) expression in activated T cells. NFAT has been
      previously reported to bind to two sites in the IL-2 promoter: in association
      with AP-1 at the distal antigen response element at -280 and at -135. On the
      basis of DNase I footprinting with recombinant NFAT and AP-1 proteins, gel shift
      assays, and transfection experiments, we have identified three additional NFAT
      sites in the IL-2 promoter. Strikingly, all five NFAT sites are essential for the
      full induction of promoter activity in response to T-cell receptor stimulation.
      Four of the five NFAT sites are part of composite elements able to bind AP-1 in
      association with NFAT. These sites display a diverse range of cooperativity and
      interdependency on NFAT and AP-1 proteins for binding. One of the NFAT sites
      directly overlaps the CD28-responsive element. We present evidence that CD28
      inducibility is conferred by the AP-1 component in NFAT-AP-1 composite elements.
      These findings provide further insight into the mechanisms involved in the
      regulation of the IL-2 promoter.

PMID- 7565785
TI  - Negative regulation of expression of the pituitary-specific transcription factor
      GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer
      elements.
AB  - Expression of the growth hormone gene is due to the presence of the pituitary
      specific transcription factor GHF-1/Pit-1. The action of the thyroid hormone T3
      is mediated by nuclear receptors that regulate transcription by interaction with
      DNA elements located near promoters of the regulated genes. In this study, we
      show that T3 inhibits expression of the GHF-1/Pit-1 gene in rat pituitary GH4C1
      cells by a novel mechanism that involves transcriptional interference with other
      regulatory elements of the promoter. Sequences between bp -90 and -200 of the rat
      GHF-1/Pit-1 gene which do not contain a hormone response element but contain two
      cyclic AMP-responsive elements mediate most of the repressive effect of T3. The
      hormone reduces basal levels of GHF-1/Pit-1 promoter activity and antagonizes its
      response to cyclic AMP and the tumor promoter TPA (12-O-tetradecanoylphorbol-13
      acetate). A similar repression is found with a heterologous promoter that
      contains four copies of the cyclic AMP-responsive element motif. This regulation
      provides a novel example of the cross-talk between the thyroid hormone receptor
      and the signal transduction pathways used by different hormones and growth
      factors. Additionally, T3 interferes with in vitro binding of GHF-1/Pit-1 to a
      positive autoregulatory element located at bp -45 to -63 and has a detectable
      inhibitory effect on the activity of a promoter construct which extends to bp -90
      of 5'-flanking DNA. The regulation of the transcription factor provides a novel
      example of negative transcriptional regulation by thyroid hormones.

PMID- 7565784
TI  - The yeast SEN3 gene encodes a regulatory subunit of the 26S proteasome complex
      required for ubiquitin-dependent protein degradation in vivo.
AB  - The yeast Sen1 protein was discovered by virtue of its role in tRNA splicing in
      vitro. To help determine the role of Sen1 in vivo, we attempted to overexpress
      the protein in yeast cells. However, cells with a high-copy SEN1-bearing plasmid,
      although expressing elevated amounts of SEN1 mRNA, show little increase in the
      level of the encoded protein, indicating that a posttranscriptional mechanism
      limits SEN1 expression. This control depends on an amino-terminal element of
      Sen1. Using a genetic selection for mutants with increased expression of Sen1
      derived fusion proteins, we identified mutations in a novel gene, designated
      SEN3. SEN3 is essential and encodes a 945-residue protein with sequence
      similarity to a subunit of an activator of the 20S proteasome from bovine
      erythrocytes, called PA700. Earlier work indicated that the 20S proteasome
      associates with a multisubunit regulatory factor, resulting in a 26S proteasome
      complex that degrades substrates of the ubiquitin system. Mutant sen3-1 cells
      have severe defects in the degradation of such substrates and accumulate
      ubiquitin-protein conjugates. Most importantly, we show biochemically that Sen3
      is a subunit of the 26S proteasome. These data provide evidence for the
      involvement of the 26S proteasome in the degradation of ubiquitinated proteins in
      vivo and for a close relationship between PA700 and the regulatory complexes
      within the 26S proteasome, and they directly demonstrate that Sen3 is a component
      of the yeast 26S proteasome.

PMID- 7565787
TI  - The amino-terminal domain of yeast U1-70K is necessary and sufficient for
      function.
AB  - The Saccharomyces cerevisiae SNP1 gene encodes a protein that shares 30% amino
      acid identity with the mammalian U1 small nuclear ribonucleoprotein particle
      protein 70K (U1-70K). We have demonstrated that yeast strains in which the SNP1
      gene was disrupted are viable but exhibit greatly increased doubling times and
      severe temperature sensitivity. Furthermore, snp1-null strains are defective in
      pre-mRNA splicing. We have tested deletion alleles of SNP1 for their ability to
      complement these phenotypes. We found that the highly conserved RNA recognition
      motif consensus domain of Snp1 is not required for complementation of the snp1
      null growth or splicing defects nor for the in vivo association with the U1 small
      nuclear ribonucleoprotein particle. However, the amino-terminal domain of Snp1,
      less strongly conserved, is necessary and sufficient for complementation.

PMID- 7565786
TI  - Rapid degradation of AU-rich element (ARE) mRNAs is activated by ribosome transit
      and blocked by secondary structure at any position 5' to the ARE.
AB  - The 3' noncoding region (NCR) AU-rich element (ARE) selectively confers rapid
      degradation on many mRNAs via a process requiring translation of the message. The
      role of cotranslation in destabilization of ARE mRNAs was examined by insertion
      of translation-blocking stable secondary structure at different sites in test
      mRNAs containing either the granulocyte-macrophage colony-stimulating factor (GM
      CSF) ARE or a control sequence. A strong (-80 kcal/mol [1 kcal = 4.184 kJ]) but
      not a moderate (-30 kcal/mol) secondary structure prevented destabilization of
      mRNAs when inserted at any position upstream of the ARE, including in the 3' NCR.
      Surprisingly, a strong secondary structure did not block rapid mRNA decay when
      placed immediately downstream of the ARE. Studies are also presented showing that
      the turnover of mRNAs containing control or ARE sequences is not altered by
      insertion of long (1,000-nucleotide) intervening segments between the stop codon
      and the ARE or between the ARE and poly(A) tail. Characterization of ARE
      containing mRNAs in polyadenylated and whole cytoplasmic RNA fractions failed to
      find evidence for decay intermediates degraded to the site of strong secondary
      structure from either the 5' or 3' end. From these and other data presented, this
      study demonstrates that complete translation of the coding region is essential
      for activation of rapid mRNA decay controlled by the GM-CSF ARE and that the
      structure of the 3' NCR can strongly influence activation. The results are
      consistent with activation of ARE-mediated decay by possible entry of translation
      linked decay factors into the 3' NCR or translation-coupled changes in 3' NCR
      ribonucleoprotein structure or composition.

PMID- 7565788
TI  - Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4
      translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary
      complexes.
AB  - To understand how phosphorylation of eukaryotic translation initiation factor
      (eIF)-2 alpha in Saccharomyces cerevisiae stimulates GCN4 mRNA translation while
      at the same time inhibiting general translation initiation, we examined the
      effects of altering the gene dosage of initiator tRNA(Met), eIF-2, and the
      guanine nucleotide exchange factor for eIF-2, eIF-2B. Overexpression of all three
      subunits of eIF-2 or all five subunits of eIF-2B suppressed the effects of eIF-2
      alpha hyperphosphorylation on both GCN4-specific and general translation
      initiation. Consistent with eIF-2 functioning in translation as part of a ternary
      complex composed of eIF-2, GTP, and Met-tRNA(iMet), reduced gene dosage of
      initiator tRNA(Met) mimicked phosphorylation of eIF-2 alpha and stimulated GCN4
      translation. In addition, overexpression of a combination of eIF-2 and tRNA(iMet)
      suppressed the growth-inhibitory effects of eIF-2 hyperphosphorylation more
      effectively than an increase in the level of either component of the ternary
      complex alone. These results provide in vivo evidence that phosphorylation of eIF
      2 alpha reduces the activities of both eIF-2 and eIF-2B and that the eIF-2.GTP.
      Met-tRNA(iMet) ternary complex is the principal component limiting translation in
      cells when eIF-2 alpha is phosphorylated on serine 51. Analysis of eIF-2 alpha
      phosphorylation in the eIF-2-overexpressing strain also provides in vivo evidence
      that phosphorylated eIF-2 acts as a competitive inhibitor of eIF-2B rather than
      forming an excessively stable inactive complex. Finally, our results demonstrate
      that the concentration of eIF-2-GTP. Met-tRNA(iMet) ternary complexes is the
      cardinal parameter determining the site of reinitiation on GCN4 mRNA and support
      the idea that reinitiation at GCN4 is inversely related to the concentration of
      ternary complexes in the cell.

PMID- 7565790
TI  - Conserved intron elements repress splicing of a neuron-specific c-src exon in
      vitro.
AB  - The neuron-specific N1 exon of the mouse c-src transcript is normally skipped in
      nonneuronal cells. In this study, we examined the sequence requirements for the
      exclusion of this exon in nonneuronal HeLa cell nuclear extracts. We found that
      the repression of the N1 exon is mediated by specific intron sequences that flank
      the N1 exon. Mutagenesis experiments identified conserved CUCUCU elements within
      these intron regions that are required for the repression of N1 splicing. The
      addition of an RNA competitor containing the upstream regulatory sequence to the
      HeLa extract induced splicing of the intron downstream of N1, indicating that the
      competitor sequence binds to splicing repressor proteins. The similarities
      between this mechanism for src splicing repression and the repression of other
      regulated exons point to a common role of exon-spanning interactions in splicing
      repression.

PMID- 7565789
TI  - Regulation of the Nur77 orphan steroid receptor in activation-induced apoptosis.
AB  - T-cell receptor (TCR)-mediated apoptosis in immature thymocytes and T-cell
      hybridomas is calcium dependent and can be inhibited by cyclosporin A (CsA).
      Induction of the orphan steroid receptor Nur77 (NGFI-B) is required for
      activation-induced apoptosis. Here, we examined the regulation of Nur77
      expression, in response to apoptotic TCR signals, which consists of kinase C and
      calcium pathways. We show that the major control of Nur77 induction is mediated
      by the calcium signaling pathway. In contrast, protein kinase C signals induce
      only a low level of Nur77 activity. Nur77 promoter activity parallels its protein
      levels. CsA decreases both Nur77 protein levels and promoter activity, and the
      kinetics of CsA inhibition of apoptosis correlates with a decrease in Nur77
      protein levels. TCR signals and kinase C signals result in a similar level of
      Nur77 protein phosphorylation but mediate differential transactivation activity
      of Nur77. In addition, Nur77 promoter deletion analysis revealed two RSRF
      (related to serum-responsive factor) binding sites, which can confer calcium and
      CsA sensitivity on a heterologous promoter. Taken together, our data suggest that
      the levels of transcriptional induction of Nur77 play an important role during
      activation-induced apoptosis and that calcium signals regulate a novel CsA
      sensitive nuclear factor required for Nur77 transcription in T cells.

PMID- 7565791
TI  - Doxorubicin-induced Id2A gene transcription is targeted at an activating
      transcription factor/cyclic AMP response element motif through novel mechanisms
      involving protein kinases distinct from protein kinase C and protein kinase A.
AB  - We have recently shown that doxorubicin (Dox), an antineoplastic drug and an
      inhibitor of terminal differentiation of myogenic and adipogenic cells, induces
      expression of Id, a gene encoding a helix-loop-helix transcriptional inhibitor.
      In this study we have investigated the molecular mechanisms underlying Dox
      induced Id2A expression. We have also attempted to determine whether the genetic
      responses to Dox are related to the UV response, a well-characterized set of
      reactions to UV and DNA-damaging compounds that is partly mediated by AP-1.
      Transient transfection of a series of deletions and point mutation derivatives of
      the human Id2A promoter sequence shows that two closely spaced and inverted short
      elements similar to an activating transcription factor (ATF) binding site or a
      cyclic AMP response element (CRE) are necessary and sufficient for a full
      response to Dox. We refer to this element as the IdATF site. Sequences containing
      an IdATF site conferred Dox inducibility on a minimal heterologous promoter. An
      electrophoretic mobility shift assay showed nuclear proteins specifically
      interacting with the IdATF sequence. While oligonucleotides containing either
      legitimate ATF/CRE or AP-1 binding sequences competed for binding, antibody
      supershift experiments suggested that neither CREB/ATF-1 nor AP-1 are major
      factors binding to IdATF. Several independent criteria suggest that Dox
      inducibility was independent of Ca2+/phospholipid-dependent protein kinase
      (protein kinase C), cyclic AMP-dependent protein kinase (protein kinase A), and
      tyrosine kinase. Moreover, we found that Dox also induces transcription from
      promoters of immediate-early genes through an AP-1-independent pathway. Taken
      together, our results suggest that Dox elicits a novel genetic response distinct
      from the classical UV response.

PMID- 7565792
TI  - Human pro-tumor necrosis factor: molecular determinants of membrane
      translocation, sorting, and maturation.
AB  - Human pro-tumor necrosis factor (pro-TNF) is a type II transmembrane protein with
      a highly conserved 76-residue leader sequence. We have analyzed the behavior,
      both in a microsomal translocational system and by transfection, of a series of
      mutants with deletions from the cytoplasmic, transmembrane, and linking domains.
      Cytoplasmic deletions included the Arg doublet at -49 and -48 and/or the Lys
      doublet at -58 and -57; additional mutants included deletion of residues -73 to 
      55 and -73 to -55, -49, and -48. The transmembrane and linking domain mutants
      included deletions in the -42 to -35 region, combined with the deletion of
      residues -32 to -1. Two hybrid mutants combined the cytoplasmic deletions with
      the deletion of residues -32 to -1. All of the cytoplasmic deletion mutants were
      properly translocated, as were the transmembrane deletion mutants with deletions
      up to residues -36, -35, -32 to -1, although the last one exhibited reduced
      efficiency; further incremental deletions, including deletions of residues -38 to
      -35 and -32 to -1, completely blocked translocation. Both hybrid mutants were
      effectively translocated; furthermore, transfection analysis revealed competent
      expression and maturation of both the cytoplasmic and hybrid mutants. Thus,
      proper expression and maturation of human pro-TNF can be accomplished with as few
      as approximately 12 of the 26 residues of the native transmembrane domain and
      with a net negative charge in the cytoplasmic domain flanking the transmembrane
      region.

PMID- 7565793
TI  - Formation of the peroxisome lumen is abolished by loss of Pichia pastoris Pas7p,
      a zinc-binding integral membrane protein of the peroxisome.
AB  - We have cloned and sequenced PAS7, a gene required for peroxisome assembly in the
      yeast Pichia pastoris. The product of this gene, Pas7p, is a member of the C3HC4
      superfamily of zinc-binding proteins. Point mutations that alter conserved
      residues of the C3HC4 motif abolish PAS7 activity and reduce zinc binding,
      suggesting that Pas7p binds zinc in vivo and that zinc binding is essential for
      PAS7 function. As with most pas mutants, pas7 cells exhibit a pronounced
      deficiency in import of peroxisomal matrix proteins that contain either the type
      1 peroxisomal targeting signal (PTS1) or the type 2 PTS (PTS2). However, while
      other yeast and mammalian pas mutants accumulate ovoid, vesicular peroxisomal
      intermediates, loss of Pas7p leads to accumulation of membrane sheets and
      vesicles which lack a recognizable lumen. Thus, Pas7p appears to be essential for
      protein translocation into peroxisomes as well as formation of the lumen of the
      organelle. Consistent with these data, we find that Pas7p is an integral
      peroxisomal membrane protein which is entirely resistant to exogenous protease
      and thus appears to reside completely within the peroxisome. Our observations
      suggest that the function of Pas7p defines a previously unrecognized step in
      peroxisome assembly: formation of the peroxisome lumen. Furthermore, because the
      peroxisomal intermediates in the pas7 delta mutant proliferate in response to
      peroxisome-inducing environmental conditions, we conclude that Pas7p is not
      required for peroxisome proliferation.

PMID- 7565794
TI  - Regulation of poly(A) site use during mouse B-cell development involves a change
      in the binding of a general polyadenylation factor in a B-cell stage-specific
      manner.
AB  - During the development of mouse B cells there is a regulated shift from the
      production of membrane to the secretion-specific forms of immunoglobulin (Ig)
      mRNA, which predominate in the late-stage or plasma B cells. By DNA transfection
      experiments we have previously shown that there is an increase in polyadenylation
      efficiency accompanying the shift to secretion-specific forms of Ig mRNA (C. R.
      Lassman, S. Matis, B. L. Hall, D. L. Toppmeyer, and C. Milcarek, J. Immunol.
      148:1251-1260, 1992). When we look in vitro at nuclear extracts prepared from
      early or memory versus late-stage or plasma B cells, we see cell stage-specific
      differences in the proteins which are UV cross-linked to the input RNAs. We have
      characterized one of these proteins as the 64-kDa subunit of the general
      polyadenylation factor cleavage-stimulatory factor (CstF) by immunoprecipitation
      of UV-cross-linked material. The amount of 64-kDa protein and its mobility on two
      dimensional gels do not vary between the B-cell stages. However, the activity of
      binding of the protein to both Ig and non-Ig substrates increases four- to
      eightfold in the late-stage or plasma cell lines relative to the binding seen in
      the early or memory B-cell lines. Therefore, the binding activity of a
      constitutive factor required for polyadenylation is altered in a B-cell-specific
      fashion. The increased binding of the 64-kDa protein may lead to a generalized
      increase in polyadenylation efficiency in plasma cells versus early or memory B
      cells which may be responsible for the increased use of the secretory poly(A)
      site seen in vivo.

PMID- 7565795
TI  - Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display
      different biological and biochemical properties in NIH 3T3 cells.
AB  - The protein kinase domains of mouse A-Raf and B-Raf were expressed as fusion
      proteins with the hormone binding domain of the human estrogen receptor in
      mammalian cells. In the absence of estradiol, 3T3 and rat1a cells expressing
      delta A-Raf:ER and delta B-Raf:ER were nontransformed, but upon the addition of
      estradiol the cells became oncogenically transformed. Morphological oncogenic
      transformation was more rapid and distinctive in cells expressing delta B-Raf:ER
      compared with cells expressing delta A-Raf:ER. Biochemical analysis of cells
      transformed by delta A-Raf:ER and delta B-Raf:ER revealed several interesting
      differences. The activation of delta B-Raf:ER consistently led to the rapid and
      robust activation of both MEK and p42/p44 MAP kinases. By contrast, the
      activation of delta A-Raf:ER led to a weak activation of MEK and the p42/p44 MAP
      kinases. The extent of activation of MEK in cells correlated with the ability of
      the different Raf kinases to phosphorylate and activate MEK1 in vitro. delta B
      Raf:ER phosphorylated MEK1 approximately 10 times more efficiently than delta Raf
      1:ER and at least 500 times more efficiently than delta A-Raf:ER under the
      conditions of the immune-complex kinase assays. These results were confirmed with
      epitope-tagged versions of the Raf kinase domains expressed in insect cells. The
      activation of all three delta Raf:ER proteins in 3T3 cells led to the
      hyperphosphorylation of the resident p74raf-1 and mSOS1 proteins, suggesting the
      possibility of "cross-talk" between the different Raf kinases and feedback
      regulation of intracellular signaling pathways. The activation of either delta B
      Raf:ER or delta Raf-1:ER in quiescent 3T3 cells was insufficient to promote the
      entry of the cells into DNA synthesis. By contrast, the activation of delta A
      Raf:ER in quiescent 3T3 cells was sufficient to promote the entry of the cells
      into S phase after prolonged exposure to beta-estradiol. The delta Raf:ER system
      has allowed us to reveal significant differences between the biological and
      biochemical properties of oncogenic forms of the Raf family of protein kinases.
      We anticipate that cells expressing these proteins and other estradiol-regulated
      protein kinases will be useful tools in future attempts to unravel the complex
      web of interactions involved in intracellular signal transduction pathways.

PMID- 7565796
TI  - Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for
      Ras transformation.
AB  - Although substantial evidence supports a critical role for the activation of Raf
      1 and mitogen-activated protein kinases (MAPKs) in oncogenic Ras-mediated
      transformation, recent evidence suggests that Ras may activate a second signaling
      pathway which involves the Ras-related proteins Rac1 and RhoA. Consequently, we
      used three complementary approaches to determine the contribution of Rac1 and
      RhoA function to oncogenic Ras-mediated transformation. First, whereas
      constitutively activated mutants of Rac1 and RhoA showed very weak transforming
      activity when transfected alone, their coexpression with a weakly transforming
      Raf-1 mutant caused a greater than 35-fold enhancement of transforming activity.
      Second, we observed that coexpression of dominant negative mutants of Rac1 and
      RhoA reduced oncogenic Ras transforming activity. Third, activated Rac1 and RhoA
      further enhanced oncogenic Ras-triggered morphologic transformation, as well as
      growth in soft agar and cell motility. Finally, we also observed that kinase
      deficient MAPKs inhibited Ras transformation. Taken together, these data support
      the possibility that oncogenic Ras activation of Rac1 and RhoA, coupled with
      activation of the Raf/MAPK pathway, is required to trigger the full morphogenic
      and mitogenic consequences of oncogenic Ras transformation.

PMID- 7565800
TI  - Presence of exon splicing silencers within human immunodeficiency virus type 1
      tat exon 2 and tat-rev exon 3: evidence for inhibition mediated by cellular
      factors.

PMID- 7565797
TI  - Feedback inhibition of the yeast ribosomal protein gene CRY2 is mediated by the
      nucleotide sequence and secondary structure of CRY2 pre-mRNA.
AB  - The Saccharomyces cerevisiae CRY1 and CRY2 genes, which encode ribosomal protein
      rp59, are expressed at a 10:1 ratio in wild-type cells. Deletion or inactivation
      of CRY1 leads to 5- to 10-fold-increased levels of CRY2 mRNA. Ribosomal protein
      59, expressed from either CRY1 or CRY2, represses expression of CRY2 but not
      CRY1. cis-Acting elements involved in repression of CRY2 were identified by
      assaying the expression of CRY2-lacZ gene fusions and promoter fusions in CRY1
      CRY2 and cry1-delta CRY2 strains. Sequences necessary and sufficient for
      regulation lie within the transcribed region of CRY2, including the 5' exon and
      the first 62 nucleotides of the intron. Analysis of CRY2 point mutations
      corroborates these results and indicates that both the secondary structure and
      sequence of the regulatory region of CRY2 pre-mRNA are necessary for repression.
      The regulatory sequence of CRY2 is phylogenetically conserved; a very similar
      sequence is present in the 5' end of the RP59 gene of the yeast Kluyveromyces
      lactis. Wild-type cells contain very low levels of both CRY2 pre-mRNA and CRY2
      mRNA. Increased levels of CRY2 pre-mRNA are present in mtr mutants, defective in
      mRNA transport, and in upf1 mutants, defective in degradation of cytoplasmic RNA,
      suggesting that in wild-type repressed cells, unspliced CRY2 pre-mRNA is degraded
      in the cytoplasm. Taken together, these results suggest that feedback regulation
      of CRY2 occurs posttranscriptionally. A model for coupling ribosome assembly and
      regulation of ribosomal protein gene expression is proposed.

PMID- 7565799
TI  - Reversal of in vitro p53 squelching by both TFIIB and TFIID.
AB  - p53, the protein encoded by one of the most significant human tumor suppressor
      genes, is a sequence-specific transcriptional activator. When activated by a
      double-stranded DNA break, p53 function arrests cells in G1 and can induce
      apoptosis. Transcriptional activation function is critical for p53 tumor
      suppression, although transcriptional repressing and nontranscriptional functions
      of p53 may contribute. p53 activation requires that it bind to TFIID through
      interactions with TATA box-binding protein (TBP)-associated factors and
      potentially with TBP. Here, we studied the mechanism of p53 activation using in
      vitro transcription and a sufficiently high p53 concentration to squelch
      activated transcription. Squelching is thought to result when target molecules
      that interact with activation domains are titrated by binding to excess
      activator. Addition of either excess TFIIB or TFIID but not other proteins
      required for p53-activated transcription reversed squelching by high p53
      concentrations, whereas neither stimulated transcription in reactions without
      excess p53. These results reveal that both TFIIB and TFIID are inhibited by high
      concentrations of p53 and suggest that p53 activation may work through direct or
      indirect interactions with both TFIIB and TFIID.

PMID- 7565798
TI  - A class of activation domains interacts directly with TFIIA and stimulates TFIIA
      TFIID-promoter complex assembly.
AB  - TFIIA is a general transcription factor that interacts with the TFIID-promoter
      complex required for transcription initiation by RNA polymerase II. Two lines of
      evidence suggest that TFIIA is directly involved in the mechanism by which some
      activators stimulate transcription. First, binding of TFIIA to a TFIID-promoter
      complex is a rate-limiting step that is enhanced by transcriptional activators
      GAL4-AH and Zta. Second, recombinant TFIIA greatly enhances activator-dependent
      transcription. In this study, we found that the activation domains of Zta and
      VP16 bind directly to TFIIA. Both Zta and VP16 stimulated rapid assembly of a
      stable TFIID-TFIIA complex on promoter DNA. Analysis of deletion derivatives of
      the VP16 activation domain indicated that the ability to bind to TFIIA correlates
      with the ability to enhance TFIID-TFIIA-promoter ternary complex assembly. Thus,
      we propose that a class of activators stimulate transcription initiation through
      direct interactions with both TFIIA and TFIID, which stimulate the assembly of an
      activated TFIIA-TFIID-promoter complex.

PMID- 7565801
TI  - Single strand DNA-binding proteins and thyroid transcription factor-1 conjointly
      regulate thyrotropin receptor gene expression.
AB  - An element, -186 to -176 base pairs (bp), in the minimal TSH receptor (TSHR)
      promoter binds thyroid transcription factor-1 (TTF-1) and is important for both
      constitutive expression and TSH/cAMP-induced negative autoregulation of the TSHR
      in thyroid cells. An element on the noncoding strand of the TSHR, contiguous with
      the 5'-end of the TTF-1 element, has single strand binding activity. It is
      distinct from the TTF-1 site, as evidenced by competition experiments using gel
      shift assays; but the association of the two elements is not random. Thus, the
      single strand binding protein (SSBP) element also exists contiguous to the 5'-end
      of an upstream TTF-1 site, -881 to -866 bp; mutation of two conserved nucleotides
      in each SSBP element results in the loss of SSBP binding and cross-competition.
      Transfection experiments indicate that full, constitutive TSHR gene expression in
      FRTL-5 thyroid cells requires the binding of both SSBPs and TTF-1, since mutation
      of either element halves thyroid-specific promoter activity, whereas mutation of
      both decreases promoter activity to values near those of a control vector.
      Transfection experiments with rat liver cells support their independent
      activities and show that the SSBP site contributes to TSHR gene expression in non
      thyroid tissue. The SSBPs function conjointly with TTF-1 in thyroid-specific,
      TSH/cAMP-induced negative autoregulation of the TSHR. Thus, TSH or forskolin
      treated FRTL-5 cells coordinately decrease TSHR RNA levels and TSHR DNA binding
      to both the SSBPs and TTF-1; also the maximal TSH/cAMP-induced decrease in gene
      expression requires both elements. The TSH-induced effect in each case is
      inhibited by cycloheximide; the TSH-induced decrease in SSBP/DNA complex
      formation requires the presence of insulin or calf serum, exactly as does TSH
      induced down-regulation of TSHR RNA levels. In sum, full, constitutive expression
      of the TSHR in thyroid cells requires TTF-1 and the SSBPs to bind separate,
      contiguous elements on the TSHR promoter. TSH/cAMP decreases the binding of each
      factor to its respective site, thereby decreasing TSHR gene expression. The role
      of the SSBP and TTF-1 sites in constitutive TSHR expression and in TSH/cAMP
      induced negative regulation of the TSHR is, therefore, additive and independent.

PMID- 7565802
TI  - The human thyrotropin-releasing hormone gene is regulated by thyroid hormone
      through two distinct classes of negative thyroid hormone response elements.
AB  - TRH is the principal positive regulator of TSH synthesis and secretion in man. T3
      is able to control TRH synthesis through feedback inhibition at the
      transcriptional level, presumably by binding to its receptor which interacts with
      one or more negative thyroid hormone response elements (TREs) present within the
      human TRH promoter. In the present study we have identified the specific negative
      TREs within the TRH promoter and characterized their ability to interact with
      thyroid hormone receptors (TRs), and the retinoid X receptor (RXR). Our analysis
      demonstrates that ligand-independent and dependent regulation of the human TRH
      promoter is restricted to the TR beta 1 isoform. Deletional analysis of the TRH
      promoter identified two discrete regions that are responsible for mediating
      ligand-dependent negative regulation of the TRH promoter. Mutagenesis of
      potential TR binding half-sites within these regions identified three separate
      half-sites (site 4 from -55 to -60 base pairs (bp); site 5, +14 to +19 bp; and
      site 6, +37 to +42 bp) which act in combination to allow for negative regulation.
      Mutation and/or deletion of each of these sites leads to a loss of negative
      regulation of the TRH promoter by T3. Gel-mobility shift assays of site 4 and its
      surrounding nucleotides revealed that this region of the promoter is capable of
      binding TR monomers, homodimers, and TR-RXR heterodimers. Mutagenesis of site 4
      leads to a loss of all binding to this region. The region encompassing sites 5
      and 6 binds only TR monomer, and the addition of RXR to the binding reaction
      leads to a loss of specific monomeric binding. To assess the functional
      importance of site 4 and its surrounding nucleotides we cotransfected RXR
      isoforms along with TR beta with TRH promoter constructs containing either site 4
      or its mutant. In the presence of wild type site 4 sequence, cotransfected RXR
      enhanced negative regulation of the TRH promoter. Mutation and or deletion of
      site 4 leads to a loss of this enhancement. These data demonstrate that two
      structurally different negative TREs cooperate to allow for negative regulation
      of the human TRH promoter and that negative regulation is TR isoform-specific and
      modulated by the RXR-signaling pathway through a novel negative TRE.

PMID- 7565803
TI  - Role of the N terminus in DNA recognition by the v-erb A protein, an oncogenic
      derivative of a thyroid hormone receptor.
AB  - The v-erb A oncogene is a mutated derivative of a normal cellular locus (c-erb A
      alpha) encoding a thyroid hormone receptor. Although both the v-erb A protein and
      thyroid hormone receptor bind to DNA, the DNA sequence specificity of the viral
      oncoprotein is altered from that of the normal cellular receptor. Intriguingly,
      amino acid differences in both the zinc-finger domain and in a less-characterized
      N-terminal region of the v- and c-erb A polypeptides are jointly responsible for
      these differences in DNA specificity. We demonstrate here that this newly
      recognized N-terminal determinant of DNA specificity appears to function by
      restricting the DNA sequence repertoire manifested by the zinc-finger domain
      itself. The unique presence of a tyrosine in the N terminus of the thyroid
      hormone receptor acts to abrogate this restriction, thereby permitting this
      receptor to utilize response elements containing nonconsensus half-sites. The
      ability of the N terminus to modulate the DNA recognition properties of nuclear
      hormone receptors extends to the retinoic acid receptor and contributes to the
      distinct DNA specificities displayed by the retinoic acid and thyroid hormone
      receptors.

PMID- 7565804
TI  - Thyroid hormone receptor homodimers can function as ligand-sensitive repressors.
AB  - Unlike the steroid hormone receptors that bind their response elements as
      homodimers, thyroid hormone receptor (TRs) as well as retinoic acid receptors and
      several other receptors have been shown to require heterodimerization with
      retinoid X receptors (RXR) for efficient binding to most response elements. In
      this article we have compared in detail TR DNA binding and its gene-regulatory
      characteristics in the presence and absence of RXR. We observe that in the
      absence of RXR, TRs are able to bind with high affinity as homodimers to a subset
      of thyroid hormone response elements consisting of two AGGTCA motifs arranged as
      inverted palindromes. This binding is inhibited by T3, which prevents TR
      homodimers from functioning as ligand-dependent transcriptional activators. We
      demonstrate that TR homodimers can act as potent ligand-responsive repressors, in
      particular when binding to sites 3' of the TATA box. Thus, TRs appear to have
      important regulatory functions in the absence of RXRs. This is strongly supported
      by our observations that some naturally occurring TR beta mutants that have been
      associated with generalized thyroid hormone resistance as well as the v-erbA
      oncogene are defective in this activity. Thus ligand-sensitive repression by TRs
      is an important regulatory mechanism.

PMID- 7565806
TI  - Studies using fluorescent tetrahydrochrysene estrogens for in situ visualization
      of the estrogen receptor in living cells.
AB  - We have analyzed four fluorescent nonsteroidal estrogens for their potential to
      serve as vital cytological stains to visualize the estrogen receptor (ER) in a
      model receptor expression system. The novel estrogen fluorophores are based on
      the rigidified stilbene-like structure of 5,6,11,12-tetrahydrochrysene (THC), and
      they embody electron-donor (hydroxyl) and electron-acceptor groups (nitrile,
      amide, ester, or ketone) that afford efficient, long wavelength, and environment
      sensitive fluorescence. These probes bind with high affinity to human ER
      (relative binding affinity, 22-85 vs. estradiol, 100), and they stimulate the
      transcriptional activity of this receptor. The strong fluorescence of the
      estrogenic THCs permits visualization, using conventional epifluorescence
      microscopy, of ER in transfected Cos-7 cells that express elevated levels of
      receptor. Cell staining by the donor-acceptor THCs characteristically displays a
      nonuniform pattern of nuclear fluorescence that can be fully inhibited by
      nonfluorescent estrogens such as estradiol or diethylstilbestrol. Additionally,
      this staining appears to be specific for ER, since it coincides with the
      distribution of receptor as determined by indirect immunofluorescence analysis
      using an ER-specific monoclonal antibody. Using these probes, we have analyzed
      the intracellular distribution of ER mutants containing a variety of deletions.
      Evidence is presented to show that removal of amino-terminal sequences within the
      ER polypeptide results in an altered pattern of intranuclear distribution with
      preferential accumulation of receptor protein within the nucleolus. These THC
      fluorophores therefore represent excellent probes for cytological studies
      involving ER expressed in cultured cells and represent an important advance
      toward the goal of exploiting fluorescence technology to analyze the expression
      and distribution of ER within tissue samples.

PMID- 7565807
TI  - Identification of three proline-directed phosphorylation sites in the human
      androgen receptor.
AB  - Full-length wild type and deletion mutant human androgen receptors (AR) were
      transiently expressed in monkey kidney COS cells to identify the phosphorylated
      amino acid residues. Phosphoamino acid analysis indicated serine (Ser) and
      threonine (Thr) residues as the major sites of phosphorylation. Both NH2- and
      carboxyl-terminal fragments containing the DNA-binding domain were highly
      phosphorylated, suggesting the presence of phosphorylation sites throughout the
      protein. Site-directed mutagenesis of wild type and deletion mutant AR at proline
      directed consensus phosphorylation sites replaced Ser or Thr residues with Ala;
      wild type and mutant ARs were expressed in the presence of [32P]orthophosphate
      and isolated by immunoprecipitation using AR-specific antipeptide antibodies.
      Three proline-directed phosphorylation sites were identified: Ser 81 and 94 in
      the NH2-terminal region and Ser 650 in the hinge region. Expression of a series
      of NH2-terminal AR fragments provided evidence for additional sites in the NH2
      terminal region. The effect of loss of each phosphorylation site on receptor
      function was determined by introducing the Ser to Ala mutations into full-length
      AR. Substituting Ser 81 and 94 with Ala had little effect on transcriptional
      activity when assayed by transient cotransfection. Substituting Ser 650 with Ala
      in the hinge region reduced transcriptional activity up to 30%. The results
      suggest at least three proline-directed phosphorylation sites in AR, one of
      which, serine 650, contributes to optimal gene activation by AR.

PMID- 7565805
TI  - Effect of antagonists on DNA binding properties of the human estrogen receptor in
      vitro and in vivo.
AB  - Functional analyses, performed with the estrogen receptor (ER) isolated from
      different sources or produced with various expression systems, led to
      contradictory results concerning the role of estrogen (E2) and antiestrogens in
      ER DNA binding. Here we report the DNA-binding properties of the human ER and
      show that the wild type ER (HEG0) binds in vitro to an estrogen response element
      (ERE) as a dimer, irrespective of the presence or absence of estrogen. We also
      show that the two antihormones, 4-hydroxytamoxifen (OHT, a partial ER agonist)
      and ICI 164,384 (a pure antagonist) do not impair HEG0 dimerization and DNA
      binding in vitro. Exposure of HEG0 to elevated temperature (37 C) in vitro
      results in a much faster reduction of its binding capacity to an ERE in the
      absence of ligand or in the presence of ICI 164,384 than in the presence of
      either E2 or OHT. The Gly to Val mutation at amino acid 400 present in the human
      ER that we initially cloned (HE0), is responsible for an even faster heat
      inactivation of unliganded receptor compared with HEG0 and largely accounts for
      the previously observed in vitro ligand-dependent DNA binding of ER. We also show
      that, as previously observed for OHT, ICI 164,384 does not prevent ER binding to
      an ERE in vivo, even though ICI 164,384 acts as a pure antagonist for
      transcriptional activation by ER. We discuss these results in the context of a
      ligand-dependent interaction between the C-terminal region E, which contains the
      ligand-binding domain, and the N-terminal A/B region, which contains the
      activation function AF-1.

PMID- 7565809
TI  - Differential biallelic activation of three insulin-like growth factor II
      promoters in the mouse central nervous system.
AB  - Imprinting of the insulin-like growth factor II gene (IGF-II) is conserved in
      human, rat, and mouse. In human liver and chondrocytes, IGF-II transcripts from
      promoter hP1 are always derived from both parental alleles, while transcripts
      from promoters hP2-hP4 are from one parental allele. To examine the promoter
      specific imprinting pattern of mouse IGF-II, we examined IGF-II expression in F1
      generation mice derived from crossing M. spretus with M. musculus using a novel
      BsaA1 polymorphism in mouse IGF-II exon 6. There was maintenance of maternal IGF
      II imprinting in all non-central nervous system (CNS) tissues in the F1
      generation animals. However, there was biallelic expression of the IGF-II gene in
      CNS. Allelic expression of each IGF-II promoter transcript was examined by full
      length cDNA amplification with promoter-specific primers. In every tissue in
      which IGF-II was imprinted, IGF-II transcripts were derived from paternal
      promoters mP1-mP3, while the maternal allele was suppressed. In the CNS, however,
      promoters mP1-mP3 of the imprinted maternal allele became activated, leading to
      the biallelic expression of IGF-II. Moreover, the expression of IGF-II from each
      parental allele differed in various CNS regions. In leptomeninges, mP1-mP3 drive
      IGF-II expression predominantly from the paternal allele, while in some CNS
      regions, the promoter transcripts were primarily from the maternal allele. The
      coordinate regulation of mouse IGF-II promoters suggests the presence of an
      upstream imprinting complex controlling IGF-II imprinting.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7565808
TI  - Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit
      promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors
      and establishment of gonadotropin-responsive granulosa cell lines.
AB  - To establish in vivo gonadal tumor models and permanent lines of gonadal somatic
      cells we produced transgenic (TG) mice expressing the Simian virus (SV) 40 T
      antigens (T-ag), driven by 6 or 2.1 kilobase fragments of the mouse inhibin alpha
      subunit promoter. Hitherto, altogether 44 TG mice, one of which carried the
      shorter transgene, have produced gonadal tumors. Two founder females expressing
      the longer transgene, KK1 and KK3, and three established TG mouse lines were
      studied in detail. Penetrance of the phenotype in IT6-M and IT6-F mouse lines was
      100% (tumors/TG: IT6-M 22/22, IT6-F 14/14). The T-ag mRNA was strongly expressed
      in the gonads, adrenal glands, pituitary, and brain. The KK-1 and KK-3 ovarian
      tumor cells immunostained with anti-SV40 large-T antibody. The KK-1 cells
      possessed high-affinity LH receptors [equilibrium association constant (Ka = 7.8
      x 10(10) liters/mol] and responded to human CG by elevated cAMP and progesterone
      production. Also FSH slightly stimulated their cAMP and estradiol production (P <
      0.01). These cells expressed cytochrome P450arom and inhibin alpha mRNA, but not
      cytochrome P450c17 alpha. In conclusion, the KK-1 cells are immortalized
      luteinizing granulosa cells expressing endogenous gonadotropin receptors,
      steroidogenic enzymes, and inhibin alpha. These cells will be useful in studies
      on the molecular aspects of granulosa cell function. The present study indicates
      that the 6-kilobase fragment of the inhibin alpha promoter described in this
      article contains the elements directing tissue-specific expression in vivo and is
      useful for targeted expression of other genes in the gonads.

PMID- 7565810
TI  - Identification of a novel murine receptor for corticotropin-releasing hormone
      expressed in the heart.
AB  - Corticotropin-releasing hormone (CRH) is the principal regulator of the stress
      response. CRH stimulates production of ACTH via specific CRH receptors located on
      pituitary corticotropes. In addition to pituitary and central nervous system
      effects, peripheral effects of CRH have been observed involving the immune and
      cardiovascular systems. Specific CRH binding studies in several peripheral
      organs, as well as functional studies, have implied the existence of peripheral
      CRH receptors. Although a pituitary/brain CRH receptor has recently been
      identified, it is expressed at very low levels in peripheral sites where CRH
      effects have been observed. We report here the identification of a novel murine
      CRH receptor that is highly expressed in the heart. The newly cloned CRH receptor
      cDNA (CRH-R2) was isolated from a mouse heart cDNA library and encodes a 430
      amino acid protein containing seven putative transmembrane domains characteristic
      of G protein-coupled receptors. CRH-R2 is 69% identical with the previously
      identified murine pituitary CRH receptor and is encoded by a distinct gene. In
      addition to a high level of expression in the heart, weak expression was also
      observed in the brain and lungs. Functional studies using CRH-R2-transfected
      cells indicate that CRH and the CRH-related amphibian peptide, sauvagine, bind
      with high affinity to CRH-R2 and stimulate intracellular accumulation of
      cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7565811
TI  - An interferon-gamma activation sequence mediates the transcriptional regulation
      of the IgG Fc receptor type IC gene by interferon-gamma.
AB  - Expression of the IgG Fc receptor type I (Fc gamma RI) on myeloid cells is
      dramatically increased by treatment with interferon-gamma (IFN-gamma). We
      observed that Fc gamma RI transcript levels in monoblast-like U937 cells were
      elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma. Treatment of
      U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super
      induction of Fc gamma RI expression. Nuclear run-on analysis revealed that the
      rate of Fc gamma RI transcription was increased by IFN-gamma. Genomic sequence
      upstream of the Fc gamma RIC gene was cloned and subjected to primer extension
      analysis, which demonstrated a single transcription initiation site without a
      TATA box. Transient transfections of CAT reporter gene constructs containing
      various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp
      region surrounding the transcription start site (-7 to +13) was capable of
      mediating transcription initiation and that an IFN-gamma responsive element
      (GIRE) was present within 74 bp upstream of the transcription initiation site. A
      17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness
      on a heterologous promoter. Double-stranded GIRE sequence, but not a scrambled
      sequence, was specifically bound by nuclear proteins from IFN-gamma treated U937
      cells. Gel shift experiments further showed that the STAT1 alpha protein bound to
      the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells. The Fc
      gamma RIC GIRE is homologous to the IFN-gamma activation sequence (GAS) of the
      guanylate binding protein and to X box elements of class II MHC genes. Our
      results demonstrate that transcriptional regulation of the Fc gamma RIC gene by
      IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the
      proximal promoter.

PMID- 7565812
TI  - Inhibition of cytotoxic T-lymphocyte-triggered apoptosis by target cell surface
      coupled aprotinin.
AB  - A variety of recent investigations have implicated granzymes A and/or B in the
      target cell nuclear injury which accompanies cytotoxic T-lymphocyte-mediated
      cytolysis. Since soluble antiproteases have had limited efficacy in inhibiting
      CTL-mediated lysis, we developed a method to couple aprotinin, a peptide
      inhibitor of serine proteases, to the surface of target cells. Aprotinin modified
      by N-succinimidyl 3-(2-pyridyldithio)propionate retained trypsin-inhibitory
      activity, and target cells modified with aprotinin had demonstrable cell surface
      trypsin-inhibitory activity. Flow cytometry demonstrated that aprotinin was
      detectable on the target cell surface but underwent modulation at a rather rapid
      rate. When radiolabeled, aprotinin-coupled target cells were studied in 1-2 hr
      CTL assays, 51Cr release was little affected, but 125IUdR release was reduced up
      to 75% compared to controls. Corresponding apoptosis analysed by agarose gel
      electrophoresis and direct cytologic visualization was similarly reduced. Thus,
      aprotinin bound to the surface of target cells selectively protected target cells
      against CTL-mediated nuclear injury, and may serve as a model for the development
      of novel inhibitors of CTL-mediated lysis.

PMID- 7565813
TI  - Impact of the high tyrosine fraction in complementarity determining regions:
      measured and predicted effects of radioiodination on IgG immunoreactivity.
AB  - Although iodine-131 is the most widely used radionuclide for radioimmunotherapy,
      direct radiolabeling methods yield decreased immunoreactivity of the antibody as
      a function of increased iodine incorporation. We have studied the amino acid
      sequences of a therapeutic IgG (HuM195), and in particular its complementarity
      determining regions (CDR), in order to correlate the iodination of tyrosine
      residues in the antigen binding site with changes in immunoreactivity. The CDR
      contained an overabundance of tyrosines relative to an expected random
      distribution of amino acids. In contrast, lysine residues that can be used for
      ligand attachment were evenly distributed throughout the IgG. HuM195 was first
      trace labeled with 111In and then labeled with stable 127I at various specific
      activities. The immunoreactivity of each product was determined using the 111In
      tracer. The immunoreactivity measured after varying levels of iodination fit a
      theoretical curve that was generated based on the assumption that a single iodine
      incorporation anywhere on a tyrosine residue in a CDR destroys the
      immunoreactivity of the antibody. Similar theoretical curves for antibody
      fragments (Fab, Fv) suggest an even faster decrease in immunoreactivity with
      increasing iodination. A review of the sequences of other therapeutic IgG shows
      that a similar overabundance of tyrosine residues is found in the CDRs. Using
      enzyme digestion, the distribution of iodine on different parts of the antibody
      was also studied. The iodinated residues were distributed non uniformly
      throughout the IgG, with the heavy chain variable region tyrosines having a
      higher propensity for iodine incorporation than tyrosines in the other regions of
      the IgG. The common abundance of tyrosine in the CDR of IgG and its correlation
      with loss of function have important implications for therapeutic use of high
      specific activity radioiodinated monoclonal antibodies or fragments.

PMID- 7565814
TI  - A genetically engineered single-chain FV/TNF molecule possesses the anti-tumor
      immunoreactivity of FV as well as the cytotoxic activity of tumor necrosis
      factor.
AB  - Recombinant DNA techniques were used to clone, construct and express the fused
      gene FV-TNF in E. coli under control of the strong T7 bacteriophage promoter in
      the expression vector pT7-7-FV-TNF. The fusion protein FV/TNF in inclusion bodies
      from the bacteria homogenate was solubilized in the denaturing solution
      containing 6 mol/l guanidine and 0.3 mol/l DTT and refolded in refolding buffer
      containing 8 mmol/l GSSG. The FV/TNF was purified by ion exchange chromatography.
      The yield of FV/TNF was estimated at 10 mg/l. The purified FV/TNF displayed a
      single band of 42 kD under reducing conditions, whereas it showed three forms
      including its monomer (40/42 kD), its dimer (84 kD) and its trimer (126 kD) under
      non-reducing conditions. Our data showed that this fusion protein retained its
      bifunctional activities well, namely the anti-TAG72 immunoreactivity of the FV
      portion and the cytotoxic activity of the TNF moiety. Therefore, the FV/TNF
      fusion protein may prove useful in targeting the biological effect of TNF to
      tumor cells as well as in stimulating the immune destruction of tumor cells.

PMID- 7565816
TI  - Relative implication of peptide residues in binding to major histocompatibility
      complex class I H-2Db: application to the design of high-affinity, allele
      specific peptides.
AB  - The H-2Db peptide sequence SMIENLEYM was manipulated (N- and C-terminus
      truncation and alanine substitution) to determine the role of structural elements
      (peptide ends and residue side chains) in binding to H-2Db. We found that good
      binding affinity could be obtained by compensating the minimal binding condition
      for one element by the optimal condition of the other element. In particular, we
      showed, that although the minimal binding sequence could be as short as a
      heptamer (deletion of positions 1 and 2), it needed the presence of optimal amino
      acids at other positions (IENLEYM). Conversely, the structurally minimal peptide
      would accept multiple alanine residues, but required the optimal nonameric length
      (AAAENAEAA). Positions 1, 2, 3, 4, 5, 7 and 9, but not 6 and 8, were involved in
      the H-2Db-peptide interaction. Most residues interacted directly with the MHC
      molecule via their main chain (amino and carboxyl) atoms (positions 1 and 2),
      their side chains (positions 3 and 5), or both (position 9). Positions 4 and 7
      were found to play an indirect role, probably by influencing the secondary
      structure. At the C-terminus, the presence of a residue at position 9, but not
      the hydrophobic nature of its side chain, was mandatory for binding. At the N
      terminus, the role of the residue at position 1 was of either minor or critical
      importance depending on the presence or not of a strong auxiliary anchor at
      position 3. The indirect contribution of residue side chains at positions 4 and 7
      reflected the importance of dynamic components in the binding process. Based on
      these results, we designed a series of high-affinity, H-2Db selective peptides
      derived from the sequence X1 AIX4NAEAL, where X1 = Y or K and X4 = E or K. After
      radioiodination or fluorescent (FITC) labelling, these peptides bound strongly
      and specifically to the surface of viable H-2Db-expressing cells. Rationally
      designed synthetic peptides, either alone or in a stable complex with MHC, might
      be of value for controlling CTL activity.

PMID- 7565815
TI  - Regulation of interleukin-8 receptor expression in human polymorphonuclear
      neutrophils.
AB  - Interleukin-8, a neutrophil chemotactic agent, is known to have an active role in
      the induction of inflammatory response in a number of diseases. Although the
      activity of IL-8 is known to be through a receptor (IL-8R) on the surface of
      neutrophils, no information is available regarding the regulation of the IL-8R
      expression. The present study demonstrates that serum activated LPS at a
      concentration of 10 ng/ml induces expression of functionally active IL-8R by 120%
      within 30 min through de novo protein synthesis. The upregulated receptors could
      be detected by anti-IL-8R antibody and could also be demonstrated by
      autoradiography with crosslinking 125I IL-8. The serum-activated LPS-stimulated
      neutrophils migrated faster and showed higher Ca2+ flux over the unstimulated
      cells. The LPS-induced receptors were downregulated rapidly, about 85% of the
      receptor activity being lost within 90 min of incubation at 37 degrees C. The
      downregulation could be partially prevented by treatment with a cocktail of
      protease inhibitors, suggesting the possible involvement of protease(s) in this
      process. Both EDTA (100 microM) and bestatin (40 microM) afforded almost complete
      protection of the receptor from proteolytic cleavage indicating that the enzyme
      involved is a metalloprotease, possibly an aminopeptidase. The study shows that
      stimulation of PMNs with LPS leads to induction of IL-8R expression enhancing the
      IL-8-mediated biological responses and also provides evidence for post
      stimulatory restoration of receptor level on the neutrophil surface by
      proteolytic cleavage of the amino-terminal end of the receptor.

PMID- 7565817
TI  - The peptide loop consisting of amino acids 139-157 of human granzyme B
      (fragmentin 2) contains an immunodominant epitope recognized by the mouse.
AB  - Granzyme B (also termed fragmentin 2) is a prototypic member of a subfamily of
      serine proteases expressed in the cytoplasmic granules of cytotoxic T lymphocytes
      and natural killer cells, and has been implicated in the destruction of targeted
      cells. Studies on the role of all granzymes in the cytolytic response would be
      greatly facilitated by the availability of specific anti-granzyme antisera. Three
      synthetic peptides corresponding to amino acid residues 1-17, 92-109 and 139-157
      of human granzyme B were predicted to be immunogenic in the mouse, based on their
      hydrophilicity, accessibility to solvent, polymorphism with respect to mouse
      granzyme B and by comparison with X-ray crystallographic models of the rat mast
      cell protease II. Each peptide was conjugated to keyhole limpet hemocyanin and
      used to produce monoclonal antibodies in BALB/c mice. The monoclonal antibodies
      produced generally exhibited strong and specific reactivity with the respective
      immunizing peptide. However, only those antibodies detecting the peptide
      corresponding to residues 139-157 were able to detect native or denatured
      granzyme B, in direct binding studies with purified granzyme B or by
      immunoblotting. As an alternative approach for antiserum production, mice were
      immunized with whole, proteolytically active granzyme B isolated by immuno
      affinity purification from NK tumour cell lysates, using one of the monoclonal
      antibodies generated. Despite the overall structural similarities between the
      various human granzymes, these mouse antisera surprisingly reacted only with
      granzyme B. Indeed, the reactivity of these polyclonal antisera was specifically
      abrogated by preincubation with the peptide corresponding to amino acid residues
      139-157. This peptide stretch therefore represents an immunodominant portion of
      the granzyme B molecule in the mouse. Given the analogous structures of serine
      protease families expressed in leukocytes, these findings have implications for
      the production of monospecific antisera to granzymes and related proteases.

PMID- 7565818
TI  - Antibody and T-cell recognition of alpha-bungarotoxin and its synthetic loop
      peptides.
AB  - Peptides representing the loops and surface regions of alpha-bungarotoxin (BgTX)
      and control peptide analogs in which these sequences were randomized were
      synthesized and used to map the recognition profiles of the antibodies and T
      cells obtained after BgTX immunization. Also, the abilities of anti-peptide
      antibodies and T-cells to recognize the immunizing peptide and BgTX were
      determined. Three regions of BgTX were immunodominant by both rabbit and mouse
      anti-BgTX antibodies. These regions resided within loops L1 (residues 3-16), L2
      (residues 26-41) and the C-terminal tail (residues 66-74) of the toxin. The
      regions recognized by BgTX-primed T-lymphocytes were mapped in five mouse
      strains: C57BL/6(H-2b), Balb/c (H-2d), CBA (H-2k), C3H/He (H-2k) and SJL (H-2s).
      The H-2b and H-2d haplotypes were high responders to BgTX, while the H-2k and H
      2s were intermediate responders. The T-cell recognition profile of the peptides
      varied with the haplotype, consistent with Ir gene control of the responses to
      the individual regions. The submolecular specificities of antibodies and T-cells
      were compared in three of the mouse strains (C57BL/6, Balb/c and SJL). In a given
      mouse strain, there were regions that were strongly recognized by both antibodies
      and T-cells as well as regions that were predominantly recognized either by
      antibodies or by T-cells. The peptides were used as immunogens in their free form
      (i.e. without coupling to any carrier) in two of the mouse strains, Balb/c and
      SJL. In both mouse strains, the peptides gave strong antibody responses.
      Antibodies against peptide L2 showed the highest binding to intact BgTX.
      Antibodies against the other peptides exhibited lower binding activity to the
      intact toxin, and this activity was dependent on the peptide and the mouse
      strain. The response of peptide-primed T-cells to a given immunizing peptide was
      not related to whether this region was immunodominant with BgTX-primed T-cells.
      The ability of peptide-primed T-cells to recognize the intact toxin varied with
      the peptide and was dependent on the host strain. These results indicate that
      anti-peptide antibody and T-cell responses are also under genetic control and
      that their ability to cross-react with the parent toxin is not only dependent on
      the conformational exposure of the correlate region in intact BgTX.

PMID- 7565819
TI  - Did Robert Schumann have dystonia?
AB  - Occupational dystonia is a frequent clinical symptom in musicians and has been
      described as muscle spasms and hand cramps in pianists. Robert Schumann had a
      neurological impairment of his right hand that was not clinically diagnosed
      during his life and that impaired his career as pianist from his early 20s. This
      disturbance was characterized by pain and by rigidity of the fingers, which
      extended to other segments of his right upper extremity while he was performing
      and that increased with stress and improved with muscle relaxation. This
      disturbance produced a progressive impairment of his writing. We here hypothesize
      that Schumann's neurological problem was consistent with dystonia.

PMID- 7565820
TI  - Movement disorders in multiple sclerosis.
AB  - Movement disorders (MD), other than tremor, associated with multiple sclerosis
      (MS) occur infrequently. We report 14 new cases of whom nine had dystonia, three
      parkinsonism, and two had myoclonus. We also reviewed 135 such cases from the
      literature. From an analysis of the individual MDs and the site of the lesions
      described, we conclude that paroxysmal dystonias (tonic spasms), ballism/chorea,
      and palatal myoclonus can be caused by demyelinating lesions. Parkinsonism,
      dystonia, and other types of myoclonus, however, often appear to be coincidental.

PMID- 7565821
TI  - Hypokinesia in Parkinson's disease: influence of age, disease severity, and
      disease duration.
AB  - The aim of this cross-sectional study was to compare the role of aging in
      measures reflecting diurnal activity and immobility in 60 parkinsonian patients
      with predominant features of hypokinesia and rigidity and 100 healthy subjects
      aged 50 to 98 years. In the patients, we also studied the relation between
      disease duration and subjective and objective measures of disease severity. Motor
      activity was recorded during 5 successive days at home with a wrist-worn activity
      monitor. For each subject, two mean measures reflecting the diurnal activity
      level and the relative proportion of activity and immobility were calculated.
      Diurnal measures of activity revealed in both groups a prominent absolute
      reduction of activity and an increase of the time spent without movement
      ("immobility") with advancing age. Parkinsonian patients showed significantly
      lower values for both motor-activity measures than did the healthy subjects. The
      rate of the age-related decline of both diurnal activity measures in both groups,
      however, is comparable. Disease duration showed no relation with subjective and
      objective measures reflecting disease severity. This study shows that if care is
      taken to control for disease severity, the rate of the age-related decline of
      measures reflecting diurnal activity and immobility is similar in both groups.
      The lack of relation between disease duration and subjective and objective
      measures of disease severity suggests that the rate of progression of Parkinson's
      disease can be reliably studied only by means of longitudinal studies.

PMID- 7565822
TI  - Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with
      Parkinson's disease: a study of five different suppositories.
AB  - The pharmacokinetics and clinical effects of apomorphine after rectal
      administration were determined in five patients with idiopathic Parkinson's
      disease (PD). Three different pharmaceutical formulations were tested: a rectal
      solution of apomorphine (10 or 15 mg), a gelatin suppository (25 and 50 mg), and
      a Witepsol-H15 suppository (50 and 100 mg). The pharmacokinetics of apomorphine
      were determined by measuring plasma concentrations using a sensitive and specific
      high-performance liquid chromatography method. The mean bioavailability varied
      between 14.7% and 40.2%, which was the bioavailability until the end of clinical
      benefit. Also, despite the differences in dose, the values of the Cmax were
      similar, with average values of 12.7-25.6 ng/ml. Wide differences in Tmax were
      observed, with values varying between 16 min for the enema and 127.5 min for the
      Witepsol-H15 100-mg suppository. The time course of the clinical effect was
      determined by assessing the time needed for walking a 25-m course and by
      calculating a tremor and dyskinesia score. Onset of effect was similar for each
      of the preparations, with an average onset time of 14-28 min. Significant
      differences with respect to the duration of the effect were observed. The
      duration of effect after administration of the Witepsol-H15 100-mg suppository
      was 156 +/- 43 min versus 50 +/- 13 min after rectal administration of the
      apomorphine solution. These results show that rectal administration of
      apomorphine may present an alternative to subcutaneous administration. The
      sustained-release properties of the Witepsol-H15 suppositories are especially of
      interest in the treatment of on-off fluctuations in PD.

PMID- 7565823
TI  - Prevalence of focal dystonias in the western area of Tottori Prefecture in Japan.
AB  - We evaluated the prevalence of focal dystonias in the western area of Tottori
      Prefecture in Japan. The population of the area was 244,935 on October 1, 1992.
      Because four patients with blepharospasm and three patients with writer's cramp
      did not visit any hospitals or clinics in 1993 and did not reply to our question
      letter, we could not confirm their present condition: with or without focal
      dystonia in 1993. Four patients with facial dystonia including blepharospasm and
      oromandibular dystonia, seven with spasmodic torticollis, and four with writer's
      cramp were observed. The prevalence of focal dystonias was 6.12 per 100,000
      persons, which may be lower than that in western countries. Although the reasons
      for this difference are still unclear, a genetic factor may be one implication.

PMID- 7565824
TI  - The blepharospasm disability scale: an instrument for the assessment of
      functional health in blepharospasm.
AB  - Assessment of the functional status in patients with blepharospasm is of major
      importance for clinical practice and outcome studies. The Blepharospasm
      Disability Scale (BDS) is specifically directed to measure the disability in
      these patients. The metric properties of this instrument were evaluated.
      Reliability, validity, and responsiveness to within-patient health changes over
      time of the BDS were assessed in 40 patients with essential blepharospasm treated
      with botulinum toxin injections. The reliability of the scale was sufficient for
      use on group level (Cronbach's alpha coefficient, 0.69). Evidence of discriminant
      validity was provided by the difference in median score on the BDS between 21
      newly admitted patients and 19 patients already under treatment (p < 0.001).
      Convergent validity was supported by correlations between BDS and neurological
      impairment scores (range, Spearman correlation coefficients, 0.65-0.79).
      Responsiveness to health changes was demonstrated by a significant difference
      between median BDS scores before treatment and 2 weeks after treatment with
      botulinum toxin (p < 0.01). The BDS is a useful disease-specific instrument to
      assess disability. Completion of the questionnaire is easy and takes only a few
      minutes. The instrument is suitable for use in patient care, descriptive outcome
      studies, and should be considered in controlled clinical trials.

PMID- 7565825
TI  - Binswanger's disease presenting as levodopa-responsive parkinsonism:
      clinicopathologic study of three cases.
AB  - We report three cases of autopsy-proven Binswanger's disease (subcortical
      arteriosclerotic encephalopathy) with unusual clinical features. Two patients had
      supranuclear gaze disturbances, early gait dysfunction, and speech disorders
      suggestive of progressive supranuclear palsy. One of these patients was not
      demented at the time of death. The third patient had features typical of
      Parkinson's disease. All three patients were responsive to treatment with
      levodopa. The clinical spectrum of Binswanger's disease should be expanded to
      include levodopa-responsive parkinsonism.

PMID- 7565826
TI  - Click-evoked vestibulocollic reflexes in torticollis.
AB  - A total of 26 patients with torticollis were studied using a recently developed
      technique for recording vestibulocollic reflexes from the sternocleidomastoid
      muscles in addition to conventional caloric tests of vestibular function.
      Previous reports of abnormalities of vestibulo-ocular reflexes in these patients
      were confirmed with just fewer than half having significant canal pareses or
      directional preponderances (nine of 20 tested). In addition, there was a high
      incidence of abnormal click-evoked vestibulocollic reflexes (17 of 26 tested),
      which were not simply the result of prior treatment with botulinum toxin, nor due
      to unequal levels of muscle activation. In patients never previously treated with
      botulinum toxin (14 patients), the effect almost always consisted of suppressed
      responses in the sternocleidomastoid muscle ipsilateral to the direction of head
      turning. Because responses were not abnormal in all patients tested, and more
      commonly so in those with a history of torticollis of > or = 5 years (eight of
      nine patients) than in de novo patients, we suggest that the changes are more
      likely to be compensatory than causal.

PMID- 7565827
TI  - A defect of kinesthesia in Parkinson's disease.
AB  - Patients suffering from Parkinson's disease (PD) are more dependent on visual
      feedback during movement than are normals. Studying two-dimensional pointing
      movements, we recently found that PD patients undershoot targets when vision of
      their own moving hand is occluded but not when complete vision is provided or
      when the target is extinguished immediately before movement onset. In the absence
      of vision, information about position of the moving hand may originate from
      peripheral kinesthetic feedback and from corollary discharges derived from the
      efferent motor signal. To find out which of both mechanisms--kinesthetic feedback
      or corollary discharge--is defective in PD, we compared active movements with
      imposed movements in which the hand is passively moved by the experimenter,
      whereas vision of the hand was occluded under either condition. In agreement with
      our earlier findings, slow, active pointing movements of PD patients were
      hypometric. In addition, PD patients terminated passively imposed movements of
      comparable speed earlier than did normals, with the consequence that imposed
      movements were equally hypometric. Our results make it unlikely that disturbed
      corollary discharge is responsible for hypometria under nonvisual conditions.
      Instead, the data suggest that PD patients have a defect of kinesthesia in slowly
      executed movements.

PMID- 7565828
TI  - Double-blind trial of botulinum toxin for treatment of focal hand dystonia.
AB  - Ten patients with focal dystonia of the hand, all of whom had benefited in an
      open-label study of botulinum toxin, were treated with botulinum toxin-A in a
      double-blind study. Response was assessed by three measures: (a) subjective
      rating, provided by patients' reports of the effect of the injections on the
      dystonia; (b) objective testing, consisting of manual muscle testing (MRC scale)
      to measure muscle strength in all patients, timing of a writing sample and
      counting the number of errors of writing off-the-line in six patients with
      writer's cramp, counting the number of errors on a standard test of transcription
      in two patients with stenographer's cramp, and rating by professional musicians
      of the performances of two patients with musician's cramp; and (c) physicians'
      rating, provided by a review of the patients' videotaped performance by
      neurologists who were unaware of which treatment was administered. Eight of the
      10 patients had greater subjective improvement with botulinum toxin than with
      placebo, and this impression was verified by at least one objective test in six
      patients. Two patients failed to have a better response to botulinum toxin than
      to placebo, and their reports were verified by the objective tests. This study
      confirms the efficacy of botulinum toxin in many patients with focal hand
      dystonia.

PMID- 7565829
TI  - Reliance on advance information and movement sequencing in Huntington's disease.
AB  - To identify the focus of impairment in the performance of sequential movements in
      Huntington's disease (HD) patients, the extent of their reliance on external
      advance information was examined. Twelve patients with HD and their age-matched
      controls performed a series of button-presses at sequential choice points along a
      response board. A sequential pathway was designated, and with each successive
      button press, advance visual information was systematically reduced to various
      extents in advance of each move. HD patients, like previously studied
      parkinsonian patients, were particularly disadvantaged with high levels of
      reduction in advance information, and as a consequence, both their initiation and
      execution of movements progressively slowed with each successive element in the
      response sequence. The pattern of results was not affected whether or not
      patients were taking neuroleptic medication, nor did performance on a variety of
      cognitive measures correlate with motor performance. Control subjects'
      performance, on the other hand, remained constant in terms of both initiation and
      execution with each of the three levels of reduction in advance information. We
      conclude that HD patients, like parkinsonian patients, who also suffer from a
      basal ganglia (BG) disorder, require external visual cues to sequence motor
      programs effectively. Our findings suggest that with HD there may be
      abnormalities in a central mechanism that controls switching between movement
      segments within an overall motor plan. The BG, which provide internal cues
      necessary for component sequencing, may be disrupted, thereby impairing the
      ability to use such internally generated cues to guide movement.

PMID- 7565830
TI  - A family with hereditary juvenile dystonia-parkinsonism.
AB  - We report a family with autosomal dominant type hereditary juvenile dystonia
      parkinsonism in which eight members in three generations exhibited parkinsonism,
      sleep benefit, marked efficacy of levodopa, wearing-off phenomenon, and dopa
      induced choreic dyskinesia. However, one case showed mainly dystonic movement
      that worsened after administration of levodopa. The patients in this family
      showed neck dystonia, such as torticollis and retrocollis, in addition to foot
      dystonia and other dystonic movement, such as frequently lifting the thigh. From
      the family history and clinical findings, these patients are considered to have a
      specific form of hereditary dystonia-parkinsonism.

PMID- 7565831
TI  - Hemiatrophy, juvenile-onset exertional alternating leg paresis, hypotonia, and
      hemidystonia and adult-onset hemiparkinsonism: the spectrum of hemiparkinsonism
      hemiatrophy syndrome.
AB  - A 45-year-old woman with a history of probable perinatal craniocerebral trauma
      resulting in mild asymptomatic right hemiatrophy developed right leg weakness and
      hypotonia alternating with dystonia only after prolonged exertion at age 12. At
      age 27, she developed right-sided parkinsonism. Exertional paresis and dystonia
      and parkinsonism responded completely to levodopa; however, she developed a
      progressive reduction in the duration of action of levodopa over the first 4
      years of treatment. Investigations including computed tomography, magnetic
      resonance imaging, [18F]fluorodopa, and [18F]fluorodeoxyglucose positron emission
      tomography scans suggested a static lesion involving the left substantia nigra.
      This unusual exertion-induced weakness and hypotonia alternating with hypertonia
      and dystonia has not been reported previously. The role of dopamine deficiency in
      dystonia and the role of levodopa in the development of fluctuations in
      Parkinson's disease are discussed. Review of the literature, including this
      patient, emphasizes the heterogeneity of the syndrome of hemiparkinsonism
      hemiatrophy.

PMID- 7565832
TI  - Dystonia in a patient with deletion of 18q.
AB  - This is the first reported case of dystonia with a partial deletion of the long
      arm (q) of chromosome 18. Neurologic findings in the 18q- syndrome include mental
      retardation, seizures, nystagmus, incoordination, tremor, and chorea. A 36-year
      old woman with an 18q terminal deletion [karyotype 46,XX,del(18)(q22.2)] had
      hypothyroidism, diabetes mellitus, borderline intelligence, short stature, short
      neck, sensorineural hearing loss, and sensorimotor axonal neuropathy. Parents'
      karyotypes were normal. She had had incoordination and writing difficulty since
      childhood. Posturing and tremor of the head began at age 16, followed by arm
      tremors. She had jaw deviation and tremor, neck tremor with retrocollis,
      involuntary pronation of the right arm, coarse postural and severe action tremor,
      and tight pen grip with dystonic wrist extension on writing. The 18q- syndrome
      should be added to the list of genetic causes of secondary dystonia. A karyotype
      analysis should be considered in secondary dystonias, particularly when there are
      associated features such as short stature and endocrinopathies.

PMID- 7565833
TI  - Cervical dystonia due to spinal cord ependymoma: involvement of cervical cord
      segments in the pathogenesis of dystonia.
AB  - We report a patient with a progressive motor disorder dominated by pyramidal
      signs in all four extremities and cervical dystonia in the form of torticollis,
      who had imaging features of cervical cord tumor on magnetic resonance imaging
      (MRI) scanning. Ependymoma was the final diagnosis by histology. Cervical
      dystonia presenting as a manifestation of an identified focal central nervous
      system (CNS) lesion is infrequent. We believe our patient to be the first adult
      example of cervical cord tumor giving rise to cervical dystonia. Adding this
      entity to the list of differential diagnosis of torticollis is considered, and
      its mechanisms are discussed.

PMID- 7565834
TI  - Hemimasticatory spasm in hemifacial atrophy: diagnostic and therapeutic aspects
      in two patients.
AB  - We report two cases of hemimasticatory spasm in association with progressive
      hemifacial atrophy. On the basis of neurophysiological and magnetic resonance
      imaging assessments, a peripheral irritation of the trigeminal nerve--probably
      due to entrapment of the motor branches in the infratemporal fossa--is suggested
      as the cause of the involuntary movement. Local injections of botulinum toxin
      type A into the masticatory muscles proved to be a successful treatment in both
      patients.

PMID- 7565836
TI  - Reversible parkinsonism and dystonia following probable mycoplasma pneumoniae
      infection.
AB  - Infectious disease is a rare cause of parkinsonism. We report a 7-year-old boy
      who developed flu-like symptoms followed by parkinsonian features including
      hypophonia, hypomimia, bradykinesia, and dystonia. A T2-weighted brain magnetic
      resonance imaging showed high signal intensities in both basal ganglia. The
      results of serial serologic tests of Mycoplasma pneumonia antibody suggest that
      this movement disorder was associated with Mycoplasma pneumonia infection. The
      patient's symptoms gradually resolved, and the basal ganglionic lesions
      disappeared on follow-up magnetic resonance imaging.

PMID- 7565835
TI  - Auctioneer's jaw: a case of occupational oromandibular hemidystonia.
AB  - An auctioneer is described in whom focal dystonia of the jaw developed as an
      occupational symptom, occurring solely and predictably when he commenced his
      selling "patter" and resolving quickly on stopping. He responded well to
      treatment with intramuscular botulinus toxin.

PMID- 7565838
TI  - Masturbation mimicking paroxysmal dystonia or dyskinesia in a young girl.
AB  - We present the case of a young girl with periodic posturing during masturbation.
      The child had been evaluated by several physicians and underwent numerous
      diagnostic tests before the spells were seen by a physician and determined to be
      self-stimulatory and not paroxysmal dystonia. Masturbation is a normal and common
      behavior in young children and should be recognized as such. Failure to recognize
      this behavior can lead to unnecessary and invasive testing.

PMID- 7565837
TI  - Familial tremulous and myoclonic dystonia with white matter changes in brain
      magnetic resonance imaging.
AB  - We report two families with a disorder, probably autosomal recessive,
      characterized by tremor of juvenile onset, dystonia, and myoclonus with preserved
      cognitive, cerebellar, and peripheral nervous system functions. During 4 years'
      follow-up, mild spasticity appeared. Magnetic resonance imaging (MRI) revealed
      mild diffuse changes in the white matter. Central conduction times for visual,
      motor, and sensory systems were all prolonged. Extensive metabolic work-up failed
      to reveal lysosomal, peroxisomal, mitochondrial, or other metabolic
      abnormalities.

PMID- 7565839
TI  - Restless legs syndrome after a borrelia-induced myelitis.

PMID- 7565840
TI  - Hemichorea due to cryptococcal meningitis.

PMID- 7565841
TI  - Hemidystonia consequent upon ipsilateral vertebral artery occlusion and
      cerebellar infarction.

PMID- 7565842
TI  - Botulinum A toxin for the so-called apraxia of lid opening.

PMID- 7565843
TI  - The core assessment program for intracerebral transplantation.

PMID- 7565844
TI  - Familial acute dystonic-dyskinetic syndrome with dominant inheritance after use
      of antidopaminergic antiemetic drugs.

PMID- 7565845
TI  - Screening in the new environment of medicine: colon and prostate cancer.
      Introduction.

PMID- 7565846
TI  - Screening in the new environment of medicine: colon cancer.

PMID- 7565847
TI  - Screening in the new environment of medicine: prostate cancer.

PMID- 7565848
TI  - Screening in the new environment of medicine: questions and answers.

PMID- 7565849
TI  - The three mechanisms for coronary artery disease progression: insights into
      future management.
AB  - The basic mechanisms of atherosclerotic progression have been well elucidated
      during the last few years. Basic experimental and clinical information has helped
      define the three stages of progression. In this review we outline the pathologic
      and clinical differences between slow, rapid, and intermediate progression. The
      eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and
      VI) in their various stages are defined. The relationship between specific type
      of lesion and chronic endothelial injury, cardiac risk factors, and increased
      vascular permeability to lipids is noteworthy. In regard to the acute coronary
      syndromes, the fate of plaque rupture and our understanding of "passive" vs.
      "active" rupture are defined. In addition to the phenomenon of plaque rupture,
      the thrombogenicity of atherosclerotic plaques in the genesis of coronary
      syndromes is described. The combination of plaque disruption and a high
      thrombogenic risk profile--including local and systemic factors--is vital to
      understanding the genesis of the acute coronary syndromes. In approaching the use
      of these new insights to arrest or reverse the atherosclerotic process, it is
      essential to remember that the disease process starts early in life and takes
      many years to progress to the symptomatic stage. The future holds promise for the
      development of preventive strategies to halt the progression of coronary disease-
      the number one killer in the United States.

PMID- 7565850
TI  - Evolving concepts in the pathogenesis and treatment of arterial thrombosis.

PMID- 7565851
TI  - Prevention of remodeling of the heart after myocardial infarction.
AB  - Secondary prevention is critical following myocardial infarction. Infarct
      expansion leads to cardiomegaly, which may adversely affect prognosis. Infarct
      expansion seems to be associated with hypertension, anterior location, persistent
      (probably sudden) occlusion of the infarct artery, and poor collateralization.
      Prevention of cardiomegaly by angiotensin-converting-enzyme inhibitors, and
      possibly nitrates, seems to improve survival. Angiotensin-converting-enzyme
      inhibitors seem to delay the onset and the frequency of congestive failure and
      recurrent myocardial infarction.

PMID- 7565852
TI  - Personal emergency response systems: factors associated with use among older
      persons.
AB  - A descriptive survey was conducted to determine factors associated with the use
      of personal emergency response systems among older community-residing subscribers
      in the New York City metropolitan area. Subscribers who wore the portable help
      button when alone in the home were defined as being "compliant." The average
      length of time the 106 respondents (average age 83 +/- 9) had the system in their
      possession was 26 +/- 18 months. Less than 50% of the subscribers were found to
      be fully compliant. Compliance was more common in system users who had obtained
      the system themselves, had a history of falls, got positive responses to
      activations, used an assistive mobility device, and received instruction on the
      system. Compliance was less common in users who had obtained the system at the
      request of a family member. The data suggest that disuse is a common problem that
      clinicians should assess regularly to assure the benefit of this intervention.

PMID- 7565853
TI  - Increase in leukocyte adhesiveness and aggregation with stress: a model of human
      congestive heart failure.
AB  - Stress has a significant influence on the function of the human organism. A
      simple, rapid, inexpensive, and reliable marker for stress would therefore be of
      great value. We have recently noted that stress increases the state of leukocyte
      adhesiveness and aggregation in the peripheral blood. We evaluated 64 patients
      who had various degrees of congestive heart failure, a condition known to induce
      a state of physiologic stress, to verify whether a relation exists between the
      intensity of the stress response and the magnitude of leukocyte adhesiveness.
      Included in the 64 were 53 patients without congestive heart failure, 23 with
      compensated failure, 22 with significant congestive heart failure, and 19 with
      florid pulmonary edema. The percentage of aggregated leukocytes in these four
      group was 6% +/- 4%, 6% +/- 4%, 10.5% +/- 5%, and 15% +/- 14%. Values for the
      third and fourth group differed in a statistically significant way. Thus, with
      further investigation into additional stress-inducing conditions, the state of
      leukocyte adhesion and aggregation may prove to be a reliable marker for the
      detection of stress and an inexpensive tool for quantifying its severity.

PMID- 7565854
TI  - Lipomatosis of the ileocecal valve leading to episodes of partial small bowel
      obstruction.
AB  - The cases of two female patients with lipomatosis of the ileocecal valve inducing
      episodes of intestinal obstruction are presented. A barium enema with air
      contrast was performed in patient 1; patient 2 was operated on to treat ileus.
      Resection of the fatty tissue from the ileocecal valve was performed at
      operation, after histologic diagnosis on frozen section. These cases suggest that
      limited resection removing fatty tissue is effective and preferable to more
      radical resection.

PMID- 7565855
TI  - Translumbar amputation: the longest survivor--a case update.
AB  - BACKGROUND: Translumbar amputation, known also as hemicorporectomy, was first
      described by Kredel but was not performed until 10 years later in 1960. It
      appears that 44 such operations have been reported but probably several others
      remain unpublished. METHODS: The operation has been performed in 44 reported
      patients over the past 30 years in more or less the same fashion. Most have been
      done as a one-stage procedure, but the author favors laparotomy and maturation of
      urinary and fecal diversions before doing the amputation about two weeks later.
      RESULTS: Overhydration caused the death of the first three patients. This problem
      was avoided in the Memorial Sloan-Kettering patients by careful monitoring of
      central venous pressure. There were no operative deaths, but 8 of the 44 patients
      died within a month. Survival of cancer patients has not been good, but those
      with benign lesions have survived fairly well. CONCLUSION: This case is
      remarkable in that, despite a rapidly advancing cancer of the bladder, the
      patient lived for over 28 years. It is gratifying to see that other surgeons and
      patients have not abandoned this most radical of all operations when no other
      therapy can preserve life.

PMID- 7565856
TI  - Massive hemorrhage from solitary rectal ulcer: toward a definitive treatment.
AB  - Two recent cases of massive bleeding from a solitary rectal ulcer which occurred
      in patients at The Mount Sinai Hospital are presented. This unusual complication
      of a poorly understood condition has been treated in the past by a variety of
      medical and surgical approaches; no consensus has been reached. In both cases an
      abdominal rectosigmoid resection was ultimately performed after local control and
      diversion were unsuccessful. A review of the literature and a discussion of this
      new approach are presented.

PMID- 7565857
TI  - Pharmacokinetic considerations in phenytoin pharmacotherapy: preventing overdoses
      and underdoses.

PMID- 7565859
TI  - Xeroderma pigmentosum variant cells are resistant to immortalization.
AB  - Xeroderma pigmentosum (XP) is a human repair-deficient disorder that is caused by
      mutations in any of eight genes (A-G, V). The genes for complementation groups A
      G have been cloned fully or in part, but the gene for the XP variant (XPV) has
      yet to be cloned. The lack of progress with XPV is in large part due to the
      rarity of stably transformed cell lines. We have attempted to immortalize
      fibroblasts from several XPV patients to obtain cell lines with which to
      characterize this disease and clone the appropriate gene. We have found, as have
      other investigators, that this XP group is very difficult to immortalize. We used
      a variety of approaches, including transfection with pSV ori- (a plasmid
      containing the simian virus (SV) 40 large T antigen) followed by spontaneous
      transformation, which provided stable immortal lines from Cockayne syndrome A and
      B, but not from XPV; transfection with pSV ori- and exposure to 3 Gy of X-rays;
      transfection with pSV ori-, exposure to 2 Gy of X-rays, and treatment with 1 mM
      ethyl methanesulfonate; transfection with human papilloma virus-16; and infection
      with SV40. Even though we used as many as 2 x 10(8) cells in some experiments, we
      were able to immortalize only one of our lines, XP30RO. Because the biochemical
      defect in XPV cell lines involves the capacity to replicate damaged DNA
      templates, perhaps the XPV gene product could be a replication factor that
      interacts with SV40 T antigen, and whose absence from XPV cell lines presents
      difficulties for the immortalization process to proceed.

PMID- 7565858
TI  - Prostate cancer screening practices: differences between clinic and private
      patients.
AB  - How often prostate cancer screening tests are conducted in general practice is
      unknown. It is known that at the primary care level, health care delivered to
      uninsured and Medicaid patients and to privately insured patients differs. We
      investigated the frequency of digital rectal examination and prostate-specific
      antigen testing in a clinic (an internal medicine clinic) and a faculty private
      practice population at The Mount Sinai Hospital over a period of one year. A
      total of 165 male patients over 40 years of age were asked to respond to a survey
      questionnaire; 142 interviews were completed (62 private and 80 clinic). Chart
      and computer database review were used to record the last serum prostate-specific
      antigen test performed. There was no difference in age distribution between the
      two groups. The private practice patients were more likely to be insured and
      college educated, whereas the clinic patients were more likely to have no more
      than an eighth-grade education and to receive Medicaid. The two groups did not
      differ in frequency of digital examination within the past year. Private patients
      were six times more likely than clinic patients to have had prostate-specific
      antigen screening and seven times more likely to receive both of the recommended
      prostate screening tests within the past year. Results also showed that 25% of
      all patients were not screened for cancer by digital rectal examination. Study of
      a larger population is recommended to further corroborate these findings.

PMID- 7565861
TI  - Nomenclature of human genes involved in ionizing radiation sensitivity.

PMID- 7565860
TI  - A novel type of X-ray-sensitive Chinese hamster cell mutant with radioresistant
      DNA synthesis and hampered DNA double-strand break repair.
AB  - It has been shown that the Chinese hamster cell mutant V-C8 is sensitive to
      different DNA damaging agents, such as mitomycin C (MMC), alkylating agents, UV
      light, and X-rays. We found that V-C8 is also sensitive to the following
      radiomimetic agents: bleomycin (approximately 2-fold, based on D10 values), H2O2
      (approximately 2-fold), streptonigrin (approximately 11-fold), and etoposide
      (approximately 8-fold). Two independent spontaneous MMC-resistant revertants
      isolated from V-C8 cells show a level of cell killing by X-rays, EMS, and UV
      light which is similar to that of wild-type cells, suggesting that the observed
      pattern of cross-sensitivity of V-C8 cells to a wide spectrum of DNA damaging
      agents results from a single mutation. V-C8 cells also display radioresistant DNA
      synthesis following gamma-irradiation which, however, remained almost unchanged
      in the V-C8 revertants. The measurement of the level and rate of repair of DNA
      single- and double-strand breaks (SSBs and DSBs, respectively) by the DNA elution
      technique showed that the V-C8 mutant has a slower repair of DSBs induced by
      gamma-rays. The described unique phenotype of V-C8 cells suggested that V-C8
      represents a novel type of mutant amongst X-ray-sensitive hamster cell mutants.
      To confirm this, complementation analysis with other X-ray-sensitive mutants was
      performed. V-C8 cells were fused with EM9, XR-1, xrs5, sxi-1, V-3, V-E5, irs3,
      and BLM2 mutant cells, representing different complementation groups. All the
      obtained hybrids regained X-ray resistance (or bleomycin resistance in the case
      of V-C8/BLM2 hybrids) similar to that of wild-type cells, indicating that V-C8
      represents a new complementation group. The results presented indicate that V-C8
      is defective in a gene involved in a pathway operating in the responses to
      different DNA damaging agents in mammalian cells.

PMID- 7565862
TI  - DNA recombinase activity of eukaryotic DNA topoisomerase I; effects of
      camptothecin and other inhibitors.
AB  - DNA oligonucleotides containing a strong topoisomerase I cleavage site were used
      to study the DNA cleavage and strand transferase activities of calf thymus
      topoisomerase I (top1) in the absence and presence of camptothecin. A partially
      single-stranded oligonucleotide with only two nucleotides on the 3' side of the
      cleavage site (positions +1 and +2) was cleaved at the same position as the
      corresponding duplex oligonucleotide. However, cleavage in the absence of
      camptothecin was more pronounced than in the duplex oligonucleotide and was only
      partially reversible in the presence of 0.5 M NaCl, consistent with release of
      the dinucleotide 3' to the top1 break. Another reaction took place generating a
      larger DNA fragment which resulted from religation (strand transfer) of the 5'
      hydroxyl terminus of the non-scissile DNA strand to the 3' end of the top1-linked
      oligonucleotide after loss of the +1 and +2 nucleotides. Top1 religation activity
      appeared efficient since only the last 5' base of the single-stranded DNA
      acceptor was complementary to the 3' tail of the donor DNA. Religation was not
      detectable with a double-stranded DNA acceptor, which is consistent with the
      persistence of top1-induced DNA double-strand breaks in camptothecin-treated
      cells. Camptothecin and other top1 inhibitors enhanced cleavage in both the
      partially single-stranded and the duplex oligonucleotides, indicating that they
      did not inhibit the induction of top1-mediated DNA cleavage but primarily blocked
      the religation step of the enzyme catalytic cycle. The top1 DNA strand
      transferase activity was reversibly inhibited by camptothecin and several
      derivatives, as well as saintopin. These results are discussed in terms of
      camptothecin-induced DNA recombinations.

PMID- 7565863
TI  - Cell cycle arrest in response to DNA damage: lessons from yeast.

PMID- 7565864
TI  - Oxygen radical-induced single-strand DNA breaks and repair of the damage in a
      cell-free system.
AB  - Ferric nitrilotriacetate (Fe(3+)-NTA) catalyzes hydrogen peroxide-derived
      production of hydroxyl radicals, which are known to cause DNA damage. In the
      present work, Fe(3+)-NTA plus hydrogen peroxide-induced single-strand DNA breaks
      and repair of the DNA damage were studied in vitro by monitoring DNA damage- and
      DNA repair-dependent conformational changes of pUC18 plasmid DNA. Single-strand
      DNA breaks were induced in the pUC18 DNA by Fe(3+)-NTA plus hydrogen peroxide in
      a dose-dependent fashion. Induction of the DNA damage was inhibited by
      deferoxamine mesylate (an iron chelator) and by hydroxyl radical scavengers such
      as dimethyl sulfoxide (DMSO), D-mannitol and ethanol indicating that the DNA
      damage was caused by hydroxyl radicals which were generated by reaction of Fe(3+)
      NTA with hydrogen peroxide. The oxygen radical-induced single-strand DNA breaks
      were repaired partly (more than 50%) by incubating the damaged DNA at 37 degrees
      C for 3 h with a partially purified preparation of APEX nuclease (a
      multifunctional DNA repair enzyme), DNA polymerase beta, four deoxyribonucleoside
      triphosphates, T4 DNA ligase and ATP. Analyses of the partially purified
      preparation of APEX nuclease revealed that a 45-kDa protein as well as APEX
      nuclease in the preparation were involved in the repair of the single-strand DNA
      breaks. APEX nuclease was suggested to initiate the repair by removing 3' termini
      blocked by the nucleotide fragments and also by incising the 5' side of AP sites.
      The 45-kDa protein was suggested to be required for removal of the 5' tags such
      as 5'-terminal deoxyribose phosphate residues produced by the action of APEX
      nuclease on AP sites.

PMID- 7565866
TI  - Sex chromosome aneuploidy and aging.
AB  - Loss of an X chromosome in females and of the Y chromosome in males are phenomena
      associated with aging. X chromosome loss occurs in and may be limited to PHA
      stimulated peripheral lymphocytes. In males, the loss of the Y is most evident in
      bone marrow cells, but also occurs to a lesser extent in PHA stimulated
      peripheral lymphocytes. X chromosome loss is associated with premature centromere
      division leading to anaphase lag and elimination in micronuclei. The mechanism of
      Y chromosome loss has not been elucidated. No pathological consequence of either
      X or Y chromosome loss has been convincingly demonstrated. With the advent of
      FISH technology, measurement of sex chromosome aneuploidy may prove to be a
      convenient assay for cellular senecence and aging.

PMID- 7565865
TI  - Diverse capacities for the adaptive response to DNA alkylation in Bacillus
      species and strains.
AB  - Our previous studies of Bacillus subtilis showed that the genes responsible for
      the adaptive response to DNA alkylation were organized as a divergent regulon, in
      contrast to scattered operons in Escherichia coli ada regulon. To study the
      generality and diversity of gene organization, several species and strains of
      Bacillus were examined for the responsiveness to DNA alkylation. B. cereus cells
      exhibited the highest resistance to MNNG treatment. When the cells were grown in
      the presence of MNNG, 3-methyladenine DNA glycosylase and two species of DNA
      methyltransferase were induced as in B. subtilis 168 cells. B. licheniformis 749
      and B. amyloliquefaciens H cells exhibited a partial response that manifested
      itself as the induction of one species of DNA methyltransferase. On the other
      hand, B. thuringiensis var. Tohokuensis, B. megaterium KMT, and B. subtilis W23
      cells were totally deficient in this response, and were hypersensitive to
      alkylating agents. To determine the cause of this deficiency in strain W23, we
      examined the genomic structure of the corresponding region where three genes
      (alkA, adaA, and adaB) were located in 168. No homologues for the three genes
      were detected in W23 DNA by Southern hybridization. Two genes (glmS and ndhF)
      flanking the adaptive response regulon in 168 were also present in W23. A
      sequence of about 2750 bp that carried the entire regulon in 168 was replaced
      with a sequence of about 250 bp that was unique to W23. At the ends of the
      conserved segments, palindromic sequences corresponding to the transcriptional
      termination sites of the adaB and glmS genes were observed. The regulon in 168
      could be artificially replaced by the W23 sequence, and be regained through DNA
      mediated transformation.

PMID- 7565867
TI  - An investigation of antioxidant status, DNA repair capacity and mutation as a
      function of age in humans.
AB  - We are constantly exposed, throughout life, to a wide variety of extrinsic and
      intrinsic agents which have the potential to damage cellular biomolecules,
      including DNA. Imperfections in cellular defence systems which protect against
      the fixation of DNA damage can lead to an accumulation of mutations which on
      their own, or in combination with other age-related changes, may contribute to
      ageing and the development of age-related pathologies. We have previously
      reported an increase in frequency of mutation with age in human lymphocytes taken
      from healthy males in the age groups, 35-39, 50-54 and 65-69 years. In this
      article we report on the findings of a recent study which was designed to assess
      whether the age-related increase in frequency of mutation was due to a decreased
      efficacy of the defence systems against ROS-induced DNA damage, namely
      antioxidant status and DNA repair processes, in the same study subjects. In vivo
      antioxidant status was assessed in each of the study subjects by measuring blood
      levels of; superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPx;
      EC 1.11.1.9), catalase (EC 1.11.1.6), caeruloplasmin (CPL), uric acid and
      bilirubin. We did not find any statistically significant differences in the mean
      levels of these antioxidants between the three different age groups. To
      investigate the efficacy of DNA repair processes against ROS-induced DNA damage,
      an ELISA was used to quantitate DNA damage (as % single-stranded DNA; %SS-DNA) at
      various times following treatment of peripheral blood lymphocytes with hydrogen
      peroxide (H2O2). The results of this part of the study showed that in untreated
      lymphocytes, basal levels of %SS-DNA were significantly higher in individuals
      from the 65-69 years age group compared to the 35-39 years age group (p = 0.039,
      0.0013; at 5% level of significance). No significant differences were found in
      H2O2 susceptibility with age immediately following treatment (p = 0.71, 1.00; at
      5% level of significance) but a consistent and significant increase was observed
      in %SS-DNA remaining 90 min post-treatment in lymphocytes from subjects in the 65
      69 years age group, compared to %SS-DNA present in lymphocytes from the 35-39
      years age group (p = 0.013, 0.024; at 5% level of significance). The results of
      this study suggest that the age-related increase in frequency of mutations is not
      contributed to by alterations of in vivo antioxidant status with age but is by a
      decreased efficacy of the repair of ROS-induced DNA damage with age. The
      biological implications of somatic mutations in the ageing process are discussed.

PMID- 7565869
TI  - Mutation frequency in human blood cells increases with age.
AB  - Using either the colony formation assay or flow cytometry, it is feasible to
      measure the frequency of rare mutant lymphocytes or erythrocytes in human
      peripheral blood. Accordingly, we have investigated the mutant cell frequencies
      of the hypoxanthine-guanine phosphoribosyltransferase and T-cell receptor genes
      in T lymphocytes and of the glycophorin A gene in erythrocytes of several hundred
      persons aged 0-96 years. The mutant frequency of every one of these genes
      increased significantly with age. A simple accumulation of mutations in
      hematopoietic stem cells over time may explain the age-dependent increase in the
      frequency of glycophorin A mutants. In contrast, a balance between mutant cell
      generation and loss should be taken into account for the mechanism of the
      increase of T-cell mutations.

PMID- 7565868
TI  - Impact of age and environment on somatic mutation at the hprt gene of T
      lymphocytes in humans.
AB  - Analysis of two human populations for dependence of somatic mutation on age has
      revealed both similarities and differences. The studies performed employed
      peripheral blood lymphocytes and measured the efficiency with which these cells
      form clones in vitro (cloning efficiency, CE) and the frequency of cells with
      inactivating mutations of the hypoxanthine phosphoribosyltransferase gene (mutant
      frequency, MF). The people studied were between 19 and 64 years of age. In one
      population, composed of 78 never smokers and 140 current smokers from the United
      States (US), both CE and MF were dependent on age: CE declined with age (p =
      0.005); MF increased 0.15 per 10(6) cells per year of age for nonsmokers (p <
      0.001) and at 1.3 times that rate for smokers (p = 0.01). In the second
      population, 80 people of unknown smoking status from Russia, the increase in MF
      per year was even greater, 2.5 times that of the US nonsmokers (p = 0.001) but
      the dependence of CE on age was the same as for the US population (p = 0.043).
      Because the increase of MF of the Russians with age is 2-fold greater than that
      of the US smokers, the intensity of smoking and/or other environmental exposures,
      or the susceptibility to these exposures, must account for the difference in age
      dependent MF increase, not the proportion of Russians that are smokers.
      Differences in the lymphocyte subpopulations that survived the longer transit
      from Russia may have contributed to the observed differences in MF. However,
      overall, the mutant frequency results suggest that the Russians were chronically
      exposed to higher levels of agents that induce somatic mutation and that, on an
      age adjusted basis, the Russia population studied is at increased risk for health
      consequences from accumulated genetic damage.

PMID- 7565870
TI  - Genotypic selection of mitochondrial and oncogenic mutations in human tissue
      suggests mechanisms of age-related pathophysiology.
AB  - The invention of the polymerase chain reaction (PCR) has facilitated the
      development of a new class of assays to quantify human somatic mutations in vivo,
      based on genotypic selection of mutants at the DNA level rather than phenotypic
      selection of mutants at the cell level. Use of these assays has provided new
      perspectives on the timing, location and distribution of somatic mutagenesis in
      mitochondrial genes and in oncogenes of the aging human body. This descriptive
      information has led to the inference and development of new models for age
      related pathophysiology and oncogenesis. Mutations of mitochondrial genes rise
      rapidly with age to frequencies a thousand fold higher than those of nuclear
      genes. Genotypic selection analysis has revealed that mitochondrial mutations
      accumulate predominantly in non-mitotic cells whose age-dependent loss is
      associated with pathology. Random mitochondrial mutation is most likely to
      inactive Complex I, a deficiency of which induces mitochondrial superoxide
      formation and cell death. Genotypic selection of oncogenic mutations at the BCL2
      and p53 loci has revealed that the cell specificity of oncogenic mutations in
      persons without cancer correlates well with sites of tumor origin, indicating
      that cells bearing such mutations are the likely precursors of future tumors.
      Quantitative variation in human BCL2 mutation frequency is extensive, and BCL2
      mutation frequency rises with age, concordant with increased risk for lymphoma.
      The clonality and persistence of BCL2 mutations suggests two specific testable
      mechanisms of lymphomagenesis. BCL2 mutation frequency rises in persons exposed
      to cigarette smoke, and more p53 mutations occur in skin exposed to sunlight than
      in unexposed skin. Thus, in addition to their likely relevance to future cancer
      risk, the dose-response relationship between exposure and oncogenic mutations
      indicates promise for their future use as in vivo biodosimeters of human exposure
      to carcinogens.

PMID- 7565871
TI  - Human aging is associated with stochastic somatic mutations of mitochondrial DNA.
AB  - Deletions and point mutations of mitochondrial DNA (mtDNA), which are
      characteristic of various human mitochondrial diseases, have been identified
      mainly in postmitotic tissues like brain, heart and skeletal muscle of healthy
      humans of advanced age but not in young people. An exponential increase with age
      was described for deletions of mtDNA. This paper reviews the molecular basis and
      experimental results on mutations of mtDNA in patients with mitochondrial
      diseases and in aged individuals. In addition new data on the exponential
      increase of point mutations of mtDNA, characteristic for MERRF and MELAS disease,
      in extraocular muscle from elderly humans are shown. Finally the 'mitochondrial
      hypothesis on aging' based on stochastic somatic mutations of mtDNA is presented.

PMID- 7565872
TI  - Somatic mutations in the brain: relationship to aging?
AB  - Genetic instability is generally thought to underlie the process of aging and is
      predominantly associated with meiosis and mitosis. This review will discuss DNA
      damage and repair, somatic mutations and somatic recombination events in non
      dividing neurons in relation to aging. In general it can be concluded that
      mutagenesis operates at high frequency in the brain. Present data do not provide
      clear evidence for accumulating DNA damage or a change in DNA repair activity in
      the brain with age. However, a linear age-related increase in frameshift
      mutations has been shown to occur in vasopressin neurons of the rat, revealing a
      novel post-mitotic mechanism.

PMID- 7565873
TI  - Spontaneous mutant frequency of lacZ gene in spleen of transgenic mouse increases
      with age.
AB  - Spontaneous mutant frequency of lacZ gene in spleen of transgenic MutaTM mouse
      was examined at different ages. It was (3.2 +/- 1.3 (SD)) x 10(-5) at newborn and
      increased almost linearly with age up to (8.3 +/- 1.8) x 10(-5) at one year.
      Since the mutation of the gene is not likely to be subject to selection in vivo,
      the data support the idea that spontaneous mutation takes place throughout aging
      process and accumulates with age if not selected out by cell death.

PMID- 7565875
TI  - The somatic mutation theory of ageing.

PMID- 7565874
TI  - Factors affecting somatic mutation frequencies in vivo.
AB  - The factors that influence the spontaneous mutant frequencies in mammalian
      tissues have been ranked on the basis of data from our laboratory together with
      published data. Some of the data come from the endogenous hprt and Dlb-1 loci,
      but most come from transgenic mice carrying the bacterial lacI and lacZ genes in
      recoverable lambda phage vectors. Since there is evidence that these bacterial
      loci are selectively neutral, the mutant frequency observed is the integral of
      the mutation rates from the formation of the zygote. The factors that affect the
      inferred mutation rate, in decreasing order of importance are: site of
      integration of the transgene, age, tissue, and strain. Insufficient data exist to
      determine the influence of gender (probably small) and inter-laboratory variables
      (probably at least as important as age). The two most surprising results are (1)
      that about half of all mutations arise during development (and half of these in
      utero) and (2) that most somatic tissues, whether queiscent or actively
      proliferating, have similar mutant frequencies and similar increases during adult
      life.

PMID- 7565877
TI  - Nucleic acid fingerprinting by PCR-based methods: applications to problems in
      aging and mutagenesis.
AB  - There are many methods of inference in common use in biology that are based on
      population sampling, including such diverse areas as sampling organisms to
      determine the population structure of an ecosystem, sampling a set of DNA
      sequences to infer evolutionary history, sampling genetic loci to build a genetic
      map, sampling differentially expressed genes to find phenotypic markers, and many
      others. Recently developed PCR-based methods for nucleic acid fingerprinting can
      be used as sampling tools with general applicability in molecular biology,
      evolution and genetics. These methods include arbitrarily primed PCR (AP-PCR;
      Welsh and McClelland, 1990) and random amplified polymorphic DNA (RAPD; Williams
      et al., 1990) for the fingerprinting of DNA, and RNA arbitrarily primed PCR (RAP
      PCR; Welsh et al., 1992a) and differential display (DD; Liang and Pardee, 1992)
      for the fingerprinting of RNA. Novel ways of looking at genetic control are
      facilitated by the high data-acquisition capabilities of the fingerprinting
      methods. In this article, we review some of the applications of DNA
      fingerprinting to the study of mutagenesis, and of RNA fingerprinting to the
      study of normal and abnormal signal transduction. We propose that these
      fingerprinting approaches may also have applications in the study of senescence
      and aging.

PMID- 7565876
TI  - Use of transgenic mouse models for studying somatic mutations in aging.
AB  - Theories on the causes of aging, based on the accumulation of somatic mutations
      in tissues of an organism, were formulated decades ago, but remain insufficiently
      tested. Transgenic animals, equipped with integrated bacterial reporter genes
      that can be efficiently rescued from total genomic DNA of all tissues and organs,
      represent ideal tools for investigating the types and frequencies of spontaneous
      mutants accumulating during aging. The first of such systems, based on the
      transgenic integration of bacteriophage lambda shuttle vectors that contain the
      bacterial lacZ gene as mutational target, was constructed in our laboratory and
      is now routinely used. Results obtained with this and the related LacI system
      that are relevant for the somatic mutation theory of aging will be discussed. One
      conclusion is that, due to the nature of the transgene, lambda-based systems have
      the disadvantage that deletion type mutations are underrepresented in comparison
      to point mutations. To overcome those limitations, we constructed a new
      transgenic mouse model carrying a pUR288 plasmid shuttle vector with the lacZ
      reporter gene. Some preliminary data obtained with this model serve to illustrate
      its potential use to extensively test the somatic mutation theory of aging.

PMID- 7565878
TI  - DNA damage, mutation and fine structure DNA repair in aging.
AB  - The primary focus of this review is on correlations found between DNA damage,
      repair, and aging. New techniques for the measurement of DNA damage and repair at
      the level of individual genes, in individual DNA strands and in individual
      nucleotides will allow us to gain information regarding the nature of these
      correlations. Fine structure studies of DNA damage and repair in specific
      regions, including active genes, telomeres, and mitochondria have begun.
      Considerable intragenomic DNA repair heterogeneity has been found, and there have
      been indications of relationships between aging and repair in specific regions.
      More studies are necessary, however, particularly studies of the repair of
      endogenous damage. It is emphasized that the information obtained must be viewed
      from a perspective that takes into account the total responses of the cell to
      damaging events and the inter-relationships that exist between DNA repair and
      transcription.

PMID- 7565879
TI  - Deletional mutations are the basic cause of aging: historical perspectives.

PMID- 7565880
TI  - P DNA element movement in somatic cells reduces lifespan in Drosophila
      melanogaster: evidence in support of the somatic mutation theory of aging.
AB  - Evidence is presented in support of the hypothesis that P DNA element movement in
      somatic cells of Drosophila melanogaster induces genetic damage that
      significantly reduces lifespan. The lifespan of D. melanogaster males was
      significantly reduced by the somatic movement of a single P element in the
      presence of P[ry+ delta 2-3](99B) transposase. In addition, the P[ry+ SalI](89D)
      repressor of P[ry+ delta 2-3](99B) somatic transposase was observed to reduce the
      effect of P element movement on lifespan. Finally, the frequency of somatic-cell
      chromosome breakage was significantly increased in neuroblasts of males with
      somatically active P elements. These results show that lifespan in D.
      melanogaster is decreased with increased somatic genetic damage from DNA-element
      movement. Although this conclusion does not confirm that transposable element
      movement is a cause of natural senescence, this conclusion is clear evidence in
      support of a close relationship between somatic genetic damage and aging.

PMID- 7565881
TI  - Somatic movement of the mariner transposable element and lifespan of Drosophila
      species.
AB  - The effect of somatic movement of the mariner transposable element on lifespan
      was measured in Drosophila simulans and Drosophila melanogaster males at 25
      degrees C. In D. simulans this movement significantly decreased lifespan, whereas
      in D. melanogaster no correlation between transposon movement and lifespan was
      found. The results in D. simulans support the hypothesis that somatic genetic
      damage induced by DNA element movement can reduce lifespan.

PMID- 7565882
TI  - Effect of aging on spontaneous micronucleus frequencies in peripheral blood of
      nine mouse strains: the results of the 7th collaborative study organized by
      CSGMT/JEMS.MMS. Collaborative Study Group for the Micronucleus Test.
      Environmental Mutagen Society of Japan. Mammalian Mutagenesis Study Group.
AB  - The spontaneous frequencies of micronucleated reticulocytes (MNRETs) were
      examined monthly over the life spans of animals belonging to nine mouse strains
      for the 7th collaborative study organized by the CSGMT/JEMS.MMS. Both sexes of
      the BDF1 strain and females of the A/J strain showed a statistically significant
      increase in mean spontaneous MNRET frequency in their last month of life,
      suggesting the possibility of strain-specific, age-dependent chromosomal
      instability. SAMP6/Tan, an accelerated senescence-prone strain, showed the same
      tendency, although it was not statistically significant. The other strains
      studied, ddY, CD-1, B6C3F1, SAMR1, and MS/Ae, did not show significant age
      related differences in mean of MNRET frequencies. More extensive statistical
      analyses are underway, and the outcomes will be reported separately.

PMID- 7565883
TI  - Aneuploidies and micronuclei in the germ cells of male mice of advanced age.
AB  - The objective of this research was to determine whether the frequencies of
      chromosomally defective germ cells increased with age in male laboratory mice.
      Two types of chromosomal abnormalities were characterized: (1) testicular
      spermatid aneuploidy (TSA) as measured by a new method of multi-color
      fluorescence in situ hybridization (FISH) with DNA probes specific for mouse
      chromosomes X, Y and 8, and (2) spermatid micronucleus (SMN) analyses using anti
      kinetochore antibodies. B6C3F1 mice (aged 22.5 to 30.5 months, heavier than
      controls but otherwise in good health) showed significant approximately 2.0 fold
      increases in the aneuploidy phenotypes X-X-8, Y-Y-8, 8-8-X and 8-8-Y with the
      greatest effects appearing in animals aged greater than 28 months. No age effect
      was observed, however, in X-Y-8 hyperhaploidy. Major age-related increases were
      seen in Y-Y-8 and X-X-8 hyperhaploidies suggesting that advanced paternal age is
      associated primarily with meiosis II rather than meiosis I disjunction errors. A
      approximately 5 fold increase was also found in the frequency of micronucleated
      spermatids in aged mice when compared with young controls. All micronuclei
      detected in the aged animals lacked kinetochore labeling, suggesting that they
      either did not contain intact chromosomes or the chromosomes lacked detectable
      kinetochores. The findings of the TSA and SMN assays are consistent with meiotic
      or premeiotic effects of advanced age on germ cell chromosomes, but there were
      differences in the age dependencies of aneuploidy and micronuclei. In summary,
      advanced paternal age may be a risk factor for chromosomal abnormalities (both
      aneuploidy and structural abnormalities) in male germ cells.

PMID- 7565884
TI  - Dietary supplements of antioxidants reduce hprt mutant frequency in splenocytes
      of aging mice.
AB  - The level of spontaneous and gamma-radiation-induced mutations in the
      hypoxanthine-guanine phosphoribosyl-transferase (hprt) locus as well as the
      decrease in frequency of these mutations in mice of various age pretreated with
      dietary supplements of an antioxidant mixture (vitamins C, E, beta-carotene,
      rutin, selenium, zinc) were studied in splenocytes of young (8-14-week-old) and
      aged (102-110-week-old) male C57BL/6 mice. The frequency of spontaneous mutations
      in splenocytes of 102-110-week-old mice was higher by 68-88% than that in mice
      aged 8-14 weeks. On gamma-irradiation (0.5-5.0 Gy) of mice, the frequency of
      radiation-induced mutations (Vf assay) in aged mice was 2.3 to 3.6 times
      (depending on dose) higher than in young ones. Daily supplements of an
      antioxidant mixture to the diet of mice prior to irradiation showed an
      antimutagenic effect. The values of mutant frequency reduction factor (MFRF) for
      14-110-week-old mice fed with dietary antioxidants during 6 weeks prior to gamma
      irradiation with doses of 2.0 and 5.0 Gy were 5.4 and 3.7, respectively. The
      frequency of radiation-induced mutations prevented or not prevented by
      antioxidants was much higher in aged mice than in young ones.

PMID- 7565885
TI  - DNA fingerprint analysis in chemically mutagenized Chinese hamster lung cells.
AB  - Using a multi-locus minisatellite Per-6 DNA probe, we performed DNA fingerprint
      analysis. Chinese hamster lung (CHL) cells were treated with six model chemicals:
      N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C, methyl methanesulfonate,
      furylfuramide, 2-acetylamino-fluorene, and cyclophosphamide, with or without S9
      mix. 771 hypoxanthine phosphoribosyltransferase deficient clones (749 from
      mutagen-treated cells and 22 from untreated cells) and 90 unselected clones from
      untreated cells were isolated and analyzed. The spontaneous mutation frequency at
      CHL cell minisatellite loci was 0.31-0.63%. All the chemicals increased mutation
      frequencies. Almost all mutations localized to the three specific minisatellite
      loci corresponding to 4.2, 3.8, and 2.4 kb bands, suggesting that these regions
      are more unstable and susceptible to mutation. DNA fingerprint analysis is a
      promising technique for detecting mutations at neutral DNA regions, especially
      recombinational mutations, and may be useful for surveying genetic instability
      related to heritable defects or aging.

PMID- 7565886
TI  - The effects of age and lifestyle factors on the accumulation of cytogenetic
      damage as measured by chromosome painting.
AB  - Individual responses to the aging process are variable and are affected by
      genetic as well as environmental factors. Fluorescent in situ hybridization with
      whole chromosome probes ('chromosome painting') provides an efficient approach
      for detecting structural chromosome aberrations in human lymphocytes. This rapid
      and sensitive technique is an effective tool for quantifying chronic exposure to
      environmental agents which may result in an accumulation of cytogenetic damage
      with age. We have applied this technology to a normal, putatively unexposed,
      population to document the relationship between age and the accumulation of
      cytogenetic damage, as well as to establish a baseline frequency of stable
      aberrations. Using probes for chromosomes 1, 2 and 4 simultaneously, the
      equivalent of 1000 metaphases was scored for stable and unstable aberrations from
      each of 91 subjects ranging in age from newborns (umbilical cord bloods; n = 14)
      to adults aged 19 to 79 years. Each subject (or one parent of each newborn)
      completed an extensive questionnaire to identify possible lifestyle factors that
      may influence the frequency of cytogenetic damage. Our findings show a
      significant increase in stable aberrations (translocations and insertions) with
      age (p < 0.0001). We also observed age-related increases with dicentrics (p <
      0.0001) and acentric fragments (p < 0.0001). Relative to the frequencies observed
      in cord bloods, the frequencies of stable aberrations, dicentrics, and acentric
      fragments in adults aged 50 and over were elevated 10.6-fold, 3.3-fold, and 2.9
      fold, respectively. Nine variables other than age are significantly associated
      with the frequency of stable aberrations; these are: smoking (two variables),
      consumption of diet drinks and/or diet sweeteners (4 variables), exposure to
      asbestos or coal products (1 variable each), and having a previous major illness
      (1 variable). Newborns whose mothers smoked during pregnancy had a 1.5-fold
      increase in stable aberrations (p = 0.029). Repeat samples from a subset of the
      adults indicate that for most subjects there is little change in individual
      translocation frequencies over a period of two to three years. These results
      support the hypothesis that stable chromosome aberrations show a greater
      accumulation with age than do unstable aberrations and suggest that lifestyle
      factors contribute to the accumulation of cytogenetic damage.

PMID- 7565888
TI  - Fate of lesions that elicit sister chromatid exchanges (FLE-SCE) produced in DNA
      by alkylating agents in vivo.
AB  - A study was made on the effect of ethyl methanesulfonate (EMS) or
      dimethylnitrosamine (DMN) on the frequency of SCE occurring in the first, in the
      second or at the same locus in both divisions. This was done with a previously
      reported in vivo protocol which allowed us to determine the fate of lesions that
      elicit SCE (FLE-SCE) in two cell divisions after mutagen treatment. The results
      showed that EMS-induced DNA lesions that cause SCE are persistent, and that some
      of them were produced in the second-division or were generated from SCE non
      inducing lesions. We inferred this by the analysis of the response in cell
      populations. DMN seems to induce SCE mainly during the second division, but by
      inhibiting DNA synthesis as was interpreted from the cell frequency distribution
      with respect to the number of SCE in first and in second cell division.

PMID- 7565887
TI  - Chromosome aberration test for the insecticide, dichlorvos, on fish chromosomes.
AB  - Chromosome aberration test was applied for an organophosphorus insecticide,
      dichlorvos, using fish as model. Channa punctatus, an ophiocephalid, having a
      small number (2n = 32) and a rather large size of chromosomes, was used for the
      purpose. Dichlorvos, with O,O-dimethyl-2,2-dichlorovinyl phosphate as the active
      component, was dissolved in the aquarium water at concentration level equal to
      that found in drainage from agricultural fields (0.01 ppm). The chromosomal
      preparations were made from the kidney cells of the fish after 24, 48, 72 and 96
      h intervals. Controls were kept in ordinary water. The aberrations observed were
      chromatid gaps, sub-chromatid gaps, centromeric gaps, precocious separation of
      chromatids and polyploidy. These were found to be significantly higher as
      compared to that of the controls. This test proved its efficacy in the fish model
      without the administration of the chemical by injection.

PMID- 7565889
TI  - Piperonyl butoxide mutagenicity in human RSa cells.
AB  - Piperonyl butoxide (PB) is used as a pesticide synergist and food additive. Its
      chemically induced mutagenicity was found in cultured human RSa cells by
      determination of ouabain-resistant (Ouar) phenotypic mutation, with the highest
      frequency at the concentration of 0.2 microgram/ml. Moreover, K-ras codon 12
      mutations in genomic DNA, analyzed by polymerase chain reaction (PCR) and
      differential dot-blot hybridization using digoxigenin-labeled probes, were
      detected in RSa cells 6 days after exposure to PB (0.03-0.40 microgram/ml).

PMID- 7565890
TI  - Analysis of mutagenesis in UV-sensitive mouse lymphoma L5178Y-R cells with a
      polyomavirus-based shuttle vector.
AB  - A newly-developed polyomavirus-based shuttle vector, pPySLPT-2, was used to
      analyze mutations induced by UV radiation in the two related mouse lymphoma cell
      lines, L5178Y-R (LY-R) and L5178Y-S (LY-S). These well-studied cell lines differ
      in sensitivity to UV radiation, apparently due to differences in DNA repair
      capacity. Consistent with these differences, we found that replication of UV
      irradiated vector is inhibited to a greater extent in the UV sensitive LY-R cells
      than in the LY-S cells. Mutations were induced in the vector's supF target gene
      at a higher frequency in the LY-R cells than in the LY-S cells, but the sequence
      characteristics of the base substitution mutations were similar in the two cell
      lines. The pattern of UV-induced mutations in the supF target gene of this
      polyomavirus-based vector, replicated in the mouse cells, was very similar to the
      pattern observed in the same target gene in the analogous simian virus 40-based
      vector, pZ189, replicated in monkey and human cells.

PMID- 7565891
TI  - Herbicide-induced DNA damage in human lymphocytes evaluated by the single-cell
      gel electrophoresis (SCGE) assay.
AB  - The genotoxicity of the herbicides, alachlor, atrazine, maleic hydrazide,
      paraquat and trifluralin has been evaluated in the single-cell gel
      electrophoresis (SCGE) assay by using human peripheral blood lymphocytes. All
      treatments were conducted with and without the presence of an external
      bioactivation source (S9 mix). The results indicate that all the herbicides
      tested are able to give positive results by increasing the comet tail length,
      which would confirm both the genotoxicity of the herbicides and the sensitivity
      of the assay in front of these chemicals. Alachlor and atrazine give similar
      results in treatments with and without S9, while when the S9 mix was not used
      paraquat and trifluralin genotoxicity was higher. On the other hand, although
      maleic hydrazide genotoxicity was higher when S9 mix was used at normal pH (7.4),
      our data show that its genotoxicity depends largely on the pH solution,
      increasing as the pH decreased.

PMID- 7565892
TI  - Influence of soil characteristics on the clastogenic activity of maleic hydrazide
      in root tips of Vicia faba.
AB  - The clastogenic activity of the herbicide maleic hydrazide (MH) in Vicia faba
      seedlings grown in different soils was studied. In the first series of
      experiments the seedlings were treated with MH in nine soils of different
      selected properties. The second experimental protocol provided for a growth step
      in each of the nine soils under study and then for the treatment of the seedlings
      with MH in a sandy soil. The results obtained show that less clastogenic damage
      (induction of micronuclei and aberrant anatelophases) was observed in the
      seedlings treated in the soils with a high content of organic and clay-type
      colloids. A growth step carried out in the organic soils, before the treatment
      with MH, was observed to reduce the genotoxic effects of the herbicide when the
      seedlings were treated in a sandy soil. These findings suggest that some
      components of soil organic matter, such as fulvic and humic acids, may be
      absorbed by the plant roots and so carry out an antimutagenic activity against MH
      within the plant.

PMID- 7565893
TI  - Cytogenetic evaluation of the mechanism of cell death induced by the novel
      anthracenyl-amino acid topoisomerase II catalytic inhibitor NU/ICRF 500.
AB  - Anthracenyl-amino acid/dipeptides are novel topoisomerase (topo) inhibitors which
      can be actively cytotoxic in the low microM range. The present studies have been
      performed to determine whether cells treated with the topo II catalytic inhibitor
      NU/ICRF 500 (serine derivative) would manifest cytogenetic lesions consistent
      with its proposed mechanism of enzyme inhibition. Three other compounds were
      included for comparison: NU/ICRF 505 (tyrosine) which stabilises topo I cleavable
      complexes, NU/ICRF 602 (gly-gly) a non-cytotoxic catalytic inhibitor of topo I
      and II and NU/ICRF 502 (alanine) a non-cytotoxic non-topo inhibitor. Chromosomal
      damage was measured using the micronucleus test. NU/ICRF 500 (7.5-30 microM)
      induced an increase in CREST negative micronuclei (11-15 per 500 cells) in human
      lymphocytes (HL) and blocked the traverse of HL through the cell cycle, with
      cells accumulating in G2/M at 15 microM drug and G1/S at 30 microM drug. NU/ICRF
      502 was without effect in the micronucleus test. NU/ICRF 500 and 602 (90-150
      microM) caused no block in passage of synchronised metaphase Chinese hamster
      ovary cells through mitosis whereas NU/ICRF 505 produced a significant delay. DNA
      measurements of post-mitotic cells revealed that after NU/ICRF 500 treatment
      nuclei had a 4C DNA content, indicative of a lack of chromosomal segregation.
      Normal (2C) DNA content was observed with NU/ICRF 505 and 602. Overall, the data
      for NU/ICRF 500 are consistent with the cytogenetic modifications expected after
      catalytic inhibition of topo II and suggest that cell death may be mediated, at
      least in part, through this mechanism.

PMID- 7565894
TI  - Genotoxicity of the herbicide butachlor in cultured human lymphocytes.
AB  - Butachlor, a pre-emergence herbicide was investigated for its ability to induce
      sister chromatid exchanges (SCE) and chromosome aberrations (CA) in cultured
      human peripheral blood lymphocytes. Mitogen-stimulated lymphocytes were treated
      with three different concentrations (5, 10 and 20 micrograms/ml) of butachlor for
      24, 48 and 72 h. Our results indicate a dose-dependent increase in the frequency
      of chromosomal aberrations at 24, 48 and 72 h of treatment with butachlor. No SCE
      was promoted by butachlor.

PMID- 7565896
TI  - In vivo radioprotective effect of chlorophyllin on sister chromatid exchange
      induction in murine spermatogonial cells.
AB  - The radioprotective capacity of chlorophyllin was determined by measuring the
      reduction of gamma-ray-induced sister chromatid exchange (SCE) in murine
      spermatogonia in vivo. The results obtained in experiments using 100 and 200
      micrograms of chlorophyllin per gram of body weight (bw) and irradiated either
      before or after BrdU incorporation, indicate that a chlorophyllin dose of 200
      micrograms/g bw protects 100% against the induction of SCE by 0.75 Gy of gamma
      rays and 100 micrograms/g bw protects less than 50%. Chlorophyllin per se did not
      have any effect on the SCE frequency.

PMID- 7565895
TI  - Genotoxicity of the herbicide fluchloralin on human lymphocytes in vitro:
      chromosomal aberration and micronucleus tests.
AB  - Cultured human lymphocytes were exposed to three different concentrations (2.5,
      5.0 and 10.0 micrograms/ml) of fluchloralin for 24 and 48 h to assess chromosomal
      aberrations. A significant dose-dependent increase of chromatid type aberration
      was observed in these cells. Multiple aberrations (MA) were scored at all
      concentrations after 48 h treatment. To support these results we did micronucleus
      (MN) test using cytochalasin B to block cytokinesis. At lower concentrations (2.5
      to 10.0 micrograms/ml) the frequency of MN induction was not significantly
      different. Higher concentrations of fluchloralin (20, 40 and 50 micrograms/ml)
      resulted in a significant dose dependent increase in number of micronucleated
      cells. This is the first report on genotoxic effects of fluchloralin in human
      cells.

PMID- 7565898
TI  - Intrauterine growth retardation as an endpoint in mutation epidemiology: an
      evaluation based on paternal age.
AB  - Czeizel recently suggested that intrauterine growth retardation might be of value
      as a phenotypic endpoint in mutation epidemiology. We hypothesized that if some
      fraction of small-for-gestational age (SGA) births are due to new germinal
      mutations, then an association with advanced paternal age should be present. We
      evaluated the relation between paternal age and SGA, low birthweight, and preterm
      births using a large sample of births (n = 254,892) from North Carolina. The
      analyses were restricted to births of mothers aged 20-34 years and adjusted for
      maternal age, race, education, marital status, gravidity, and smoking. No
      material increase in the risk of SGA, low birthweight, and preterm delivery was
      found for fathers in any age category. For example, odds ratios for SGA ranged
      from 0.87 (fathers aged 50 years or greater) to 1.13 (fathers aged 45-49 years).
      The results indicate no discernable relationship between SGA and related
      endpoints and the increase in increase of mutations that accompany advanced
      paternal age.

PMID- 7565897
TI  - Genotoxicity of tacrine in primary hepatocytes isolated from B6C3F1 mice and aged
      ad libitum and calorie restricted Fischer 344 rats.
AB  - Tacrine (1,2,3,4-tetrahydro-9-aminoacridine; THA), a reversible centrally acting
      anticholinesterase, has been shown to be potentially useful for treatment of
      patients with Alzheimer's disease. However, currently available forms of THA may
      be therapeutically limited by the fact that high doses have resulted in liver and
      kidney damage. To determine if THA is hepatotoxic via a genotoxic mechanism, we
      evaluated its ability to induce unscheduled DNA synthesis (UDS) in primary
      cultures of rodent hepatocytes. Positive dose-dependent increases in UDS were
      observed in hepatocytes derived from male B6C3F1 mice and from young, middle
      aged, old, and old Aroclor-induced (ARO) male F344 rats maintained on either an
      ad libitum (AL) or a caloric restricted (CR) diet (60% of AL) and exposed to 0.05
      1000.0 micrograms/ml of THA. Hepatocytes from old AL rats, treated with THA,
      exhibited significant age-related decreases in DNA repair compared to young and
      middle-aged AL rats. By contrast, cultures from CR rats exhibited age- and diet
      related decreases in UDS from the AL and young CR animals, respectively.
      Moreover, ARO-induced old AL- and CR-derived hepatocytes exhibited significant
      increases in UDS compared to uninduced old AL and CR animals. No cytotoxicity was
      observed in the uninduced old AL- or any CR-derived hepatocytes. These data
      indicate that the aged and CR fed animal is less susceptible to the cytotoxic and
      genotoxic effects of THA; while the younger AL fed and enzyme induced old AL or
      CR fed animals were more susceptible. The data suggest that THA may be a
      genotoxic rodent carcinogen. At present, the relationship of these findings to
      the clinical use of THA are unclear and further study is required.

PMID- 7565899
TI  - Study on the antimutagenic effect of pine needle extract.
AB  - The micronucleus test and sister-chromatic exchange (SCE) test were used to
      research the antimutagenic effect of pine needle extract. The results showed that
      the mutagenic effect of cyclophosphamide (CP) was inhibited by the pine needle
      extract. The micronucleus frequencies (MNF) of mouse bone marrow and human
      lymphocytes from peripheral blood were decreased with the effect of the extract
      (the dose was 2000 mg/kg or 5 mg/ml); the frequency of SCE in human lymphocytes
      was also reduced significantly, which indicated that the MNF and the SCE
      frequencies were negatively correlated with the dose of pine needle extract (r = 
      0.9782, -0.9587, -0.9765, respectively). This suggested that the pine needle
      extract was an effective antimutagen and it is important to choose the proper
      doses of pine needle extract for antitumor effect.

PMID- 7565900
TI  - A comparative study of TK6 human lymphoblastoid and L5178Y mouse lymphoma cell
      lines in the in vitro micronucleus test.
AB  - Micronucleus induction was compared in human lymphoblastoid TK6 and mouse
      lymphoma L5178Y cell lines treated with model clastogens and spindle poisons,
      i.e., X-rays, methyl methanesulfonate, ethyl methanesulfonate, mitomycin C,
      colcemid, and vincristine. The spontaneous micronucleated cell (MNC) frequency
      was stable and reproducible in both cell lines. All clastogens and spindle
      poisons studied here induced micronuclei in both cell lines. They increased MNC
      frequency at lower concentrations or caused a greater increase at the same
      concentration in TK6 cells. These clastogens and spindle poisons, however, were
      also more toxic to TK6 than to L5178Y cells and when comparison was based on
      cytotoxicity, they showed more efficient MNC induction in L5178Y cells. In
      conclusion, neither cell line was superior to the other, and both of them can be
      used as target cells in the in vitro micronucleus assay.

PMID- 7565901
TI  - Formation of UV-photoadducts during DNA purification.

PMID- 7565902
TI  - Heritable translocations induced by inhalation exposure of male mice to 1,3
      butadiene.
AB  - Previously, we reported that dominant lethal mutations were induced in spermatids
      after inhalation exposure of male (102/El x C3H/El)F1 mice to 1300 ppm of 1,3
      butadiene on 5 days for 6 h per day (exposure dose 39,000 ppm h). The same
      inhalation exposure was given to male C3H/El inbred mice which were mated to
      inbred line 102/El females 8-14 d after the end of exposure. Male and female F1
      hybrid progeny were tested for the presence of heritable translocations by
      observation of litter sizes and by cytogenetic analyses in meiotic and somatic
      cells. 1,3-Butadiene induced heritable translocations in late spermatids. The
      translocation frequency after 1,3-butadiene exposure to 39,000 ppm h was 2.7% (16
      translocation heterozygotes among 559 F1 offspring). This frequency is 54 times
      higher than the historical control frequency (0.05%; 5 translocation
      heterozygotes among 9500 F1 offspring). Thus, 1,3-butadiene causes heritable germ
      cell effects in mice.

PMID- 7565903
TI  - Low environmental radiation background impairs biological defence of the yeast
      Saccharomyces cerevisiae to chemical radiomimetic agents.
AB  - Background radiation is likely to constitute one of the factors involved in
      biological evolution since radiations are able to affect biological processes.
      Therefore, it is possible to hypothesize that organisms are adapted to
      environmental background radiation and that this adaptation could increase their
      ability to respond to the harmful effects of ionizing radiations. In fact,
      adaptive responses to alkylating agents and to low doses of ionizing radiation
      have been found in many organisms. In order to test for effects of adaptation,
      cell susceptibility to treatments with high doses of radiomimetic chemical agents
      has been studied by growing them in a reduced environmental radiation background.
      The experiment has been performed by culturing yeast cells (Saccharomyces
      cerevisiae D7) in parallel in a standard background environment and in the
      underground Gran Sasso National Laboratory, with reduced environmental background
      radiation. After a conditioning period, yeast cells were exposed to
      recombinogenic doses of methyl methanesulfonate. The yeast cells grown in the
      Gran Sasso Laboratory showed a higher frequency of radiomimetic induced
      recombination as compared to those grown in the standard environment. This
      suggests that environmental radiation may act as a conditioning agent.

PMID- 7565904
TI  - Neonatal vitamin K administration and in vivo somatic mutation.
AB  - The glycophorin A (GPA) mutation assay was used to examine the risk of in vivo
      somatic mutation in infants following neonatal administration of vitamin K. The
      assay assesses damage to erythroid stem cells by measuring the frequency of NO
      and NN variant red cells of MN blood group heterozygotes using FACS analysis.
      Blood samples were obtained from 178 infants aged between 10 and 183 days. Twenty
      six children were excluded from study having received a blood transfusion. Sixty
      four of the remaining 152 infants were of the MN phenotype, samples from whom
      were analysed using the assay system, providing the first data of NO and NN
      variant frequencies (vfs) in children aged less than 1 year. Twenty of these 64
      infants received vitamin K orally (group A), 17 intramuscularly (group B) and 25
      intravenously (group C). Results were compared with those from a reference
      population of children aged 1-15 years. There were no significant differences in
      NO, NN and total vf between any of groups A, B and C. For all groups both NO and
      total vf were significantly lower than those for the control population. This
      result is of some interest and clearly warrants further investigation. NN and
      total vfs were greater than the 95th percentile for the pooled data from groups
      A, B and C in three instances, one in each group. It was thus not possible to
      demonstrate an association between the route of vitamin K administration and an
      increase in mutation at the GPA locus.

PMID- 7565905
TI  - Characterization of carboplatin-resistant sublines derived from human larynx
      carcinoma cells.
AB  - In human larynx carcinoma cells, resistance to carboplatin (CBDCA) was induced by
      continuous five-day exposure of parental lines to the increasing CBDCA
      concentrations in culture medium, reaching the clinical level of 9.23
      micrograms/ml. Three clones were selected and characterized: CBP-3, CBP-6 and CBP
      7, CBP-3 clone was 2.0-fold, CBP-6 2.1-fold, and CBP-7 2.9-fold more resistant to
      carboplatin. The response of these sublines to different cytostatics was compared
      to the response of the parental cell lines to the same drug. CBP-7 and CBP-6
      clones exhibited cross-resistance to cisplatin (cis-DDP), CBP-7 clone became
      markedly more sensitive and CBP-3 slightly more sensitive to 5-fluorouracil (5
      FU), CBP-6 became sensitive to etoposide (Et), CBP-6 became sensitive and CBP-7
      resistant to vinblastine (VBL). Other clones did not change change their
      sensitivity to cis-DDP, 5-FU, Et or VBL. None of the three clones did alter the
      sensitivity to mitomycin C, doxorubicin (Dox) or vincristine (VCR). There was no
      change in the growth rate. Glutathione (GHS) levels were elevated in all three
      clones, but the increase was significant only for CBP-7 clone. Similarly, the
      activity of glutathione transferase (GST) was elevated in all clones, but this
      increase was not significant for CBP-7 clone. The analysis of the of c-myc, c-Ha
      ras and c-fos genes reveal no change in the c-myc expression, induction of the c
      Ha-ras oncogene in CBP-6 and CBP-7 cells, and biochemistry and oncogene
      expression indicate that the acquired resistance to carboplatin is a complex,
      multifactorial process in these cells.

PMID- 7565906
TI  - Clastogenicity of anthraquinones in V79 and in three derived cell lines
      expressing P450 enzymes.
AB  - The clastogenicity of seven anthraquinones was investigated in a V79 Chinese
      hamster cell line expressing only the reductive pathway enzymes and in three
      derived cell lines transfected and expressing three rat cytochrome P450 (1A1,
      1A2, 2B1). The results have shown that chromosomal aberrations are modulated in
      similar manner both in parental and transfected V79 cell lines, suggesting that
      the clastogenicity of these compounds is not mediated by cytochrome P450
      dependent monooxygenases.

PMID- 7565907
TI  - Baseline and mitomycin C (MMC)-induced sister-chromatid exchanges in XX and XY
      cells of Callithrix jacchus chimeric twins.
AB  - Lymphocytes from chimeric individuals of the species Callithrix jacchus
      (Primates) were examined to evaluate differences in the frequency of sister
      chromatid exchanges (SCE) between XX and XY cells. The aim was to discover
      whether SCE differ according to genetic sex and whether XX and XY cells show a
      different sensitivity to SCE inducing agents. This experimental model has enabled
      us to eliminate the possible differences caused by environmental factors. The
      results obtained do not reveal significant differences between male and female
      cells, in either the baseline SCE frequency or that induced by mitomycin C at
      concentrations of 0.01 and 0.03 microgram/ml. No significant differences were
      observed in the distribution of high SCE frequency cells (HFC), even if it is
      possible to observe a higher level of exchanges in XX cells in each trial. With
      regard to the phenotypic sex, there appears to be a trend towards slightly higher
      SCE rates in females, even if results are not statistically significant.

PMID- 7565908
TI  - The pattern of adriamycin-induced mutations in V-E5 Chinese hamster cells with
      chromosomal instability.
AB  - The V-E5 cell line, a mutant V79 Chinese hamster cell line, was used to study the
      effect of chromosomal instability on the spectrum of gene mutations and
      chromosome aberrations induced by the anthracycline antibiotic adriamycin (AM). V
      E5 cells showed hypersensitivity to the cytotoxic effects of AM when compared to
      the parental cell line. AM caused both, chromosome-type aberrations and chromatid
      type aberrations in V-E5 cells. Under the same experimental conditions, gene
      mutations were induced at the hprt locus which mainly represented deletion
      mutations. The spectrum of AM-induced chromosomal aberrations and gene mutations
      did not show any peculiarities in comparison to normal V79 cells. It is concluded
      that the genomic instability in V-E5 cells does not influence the pathways
      leading to chromosome aberrations and gene mutations after AM treatment.

PMID- 7565909
TI  - Cycloheximide and buthionine sulfoximine prevent induction of genotoxic
      adaptation by cadmium salt against methyl mercuric chloride in embryonic shoot
      cells of Hordum vulgare L.
AB  - Presoaked seeds of barley Hordeum vulgare L. pretreated with cycloheximide (CH),
      10(-6) M or bythionine sulfoximine (BSO), 10(-4) M, were exposed to methyl
      mercuric chloride (MMCl), 10(-4) M, with or without prior conditioning with
      cadmium sulfate (CdSO4), 10(-4) M. Subsequently as the seeds germinated the
      endpoints measured were mitotic index, cells with mitotic aberrations and
      micronuclei (MNC) in embryonic shoot cells fixed at 40, 44, 48 and 52 h of
      recovery. Indicated by the significant reduction (p < or = 0.05) of the yield of
      cells with aberrations or MNC, the results confirmed that CdSO4-conditioning
      triggered an adaptive response to MMCl-challenge. Pretreatments of CH and BSO,
      whereas they potentiated the genotoxicity of MMCl, significantly prevented (p <
      or = 0.05) the Cd-induced genotoxic adaptation. That underscores a possible
      involvement of proteins in addition to phytochelatins in the underlaying
      mechanisms.

PMID- 7565910
TI  - On the cytotoxicity and genotoxicity of allyl and phenethyl isothiocyanates and
      their parent glucosinolates sinigrin and gluconasturtiin.
AB  - Four compounds commonly found in the human diet, allyl isothiocyanate (AITC),
      phenethyl isothiocyanate (PEITC) and their parent glucosinolates sinigrin and
      gluconasturtiin, were tested for cytotoxic and genotoxic effects in a Chinese
      hamster ovary cell line (CHO). The isothiocyanates were found to be more than one
      thousand times more cytotoxic than the glucosinolates, showing significant
      cytotoxic activity at concentrations below 1.0 microgram/ml. AITC was unable to
      induce either chromosome aberrations or sister chromatid exchanges (SCEs) even at
      highly cytotoxic doses. In contrast, PEITC was found to induce both aberrations
      and SCE at concentrations of 0.9-1.2 micrograms/ml whilst sinigrin and
      gluconasturtiin induced aberrations at concentrations above 2 mg/ml.

PMID- 7565912
TI  - High spontaneous chromosomal damage in lymphocytes from patients with hereditary
      megaduodenum.
AB  - Chromosomal aberration and micronucleus assays were used to investigate the
      extent of cytogenetic damage in peripheral blood lymphocytes from four patients
      in two unrelated families with hereditary megaduodenum. The frequencies of total
      chromosomal aberrations, which significantly correlated with those of
      micronuclei, were higher in the patients than in sex- and age-matched controls,
      with no overlapping between the two groups. The considerable chromosomal
      fragility in patients with hereditary megaduodenum may be a genotypic marker for
      preclinical diagnosis predictive of increased cancer risk.

PMID- 7565911
TI  - Influence of DNA supercoiling on cisplatin toxicity in Escherichia coli K-12.
AB  - DNA supercoiling is known to modulate the activity of numerous promoters in vitro
      and in vivo. Moreover, it has been reported to modulate the rate of formation of
      cisplatin/DNA crosslinks in vitro. In order to address the question of how the
      topology influences CDDP toxicity in E. coli, three mutants with altered gyrase
      activity which led to a decrease of about 25% in superhelical density were
      studied. Mutant strains gyrA224 and gyrB225 showed similar sensitivity to CDDP as
      the parental strain while the gyrB226 mutant was resistant. This resistance was
      abolished in uvrA (excision-repair) and recA (recombination and SOS processes)
      mutant derivatives. Thus supercoiling might play a role as an indirect modulator
      of CDDP toxicity in bacteria by interfering with repair processes.

PMID- 7565913
TI  - Effect of preinduction of metallothionein synthesis on clastogenicity of
      anticancer drugs in mice.
AB  - The effect of pretreatment with metallothionein (MT) inducers (bismuth nitrate or
      zinc chloride) on clastogenicity of anticancer drugs was investigated. Bismuth
      nitrate (50 mumol/kg) or zinc chloride (400 mumol/kg) was administered s.c. to
      mice once a day for two days prior to treatment with 3.3 mumol/kg of cis
      diamminedichloroplatinum(II) (cis-DDP), 3.4 mumol/kg of adriamycin (ADR), 72
      mumol/kg of cyclophosphamide (CPA) or 0.41 mumol/kg of L-phenylalanine mustard (L
      PAM). The frequency of occurrence of erythrocytes with micronuclei in bone marrow
      was increased by each anticancer drug at 24 h after treatment. Micronucleus
      formation was significantly prevented by pretreatment with either bismuth nitrate
      or zinc chloride. MT concentration in bone marrow cells of mice at the time of
      treatment with anticancer drugs increased to 2- and 3.5-fold by pretreatment with
      bismuth nitrate and zinc chloride, respectively. These results indicate that MT
      induction in bone marrow cells effectively prevents micronucleus induction of
      anticancer drugs.

PMID- 7565914
TI  - Variability in adaptive response to low dose radiation in human blood
      lymphocytes: consistent results from chromosome aberrations and micronuclei.
AB  - The frequencies of chromosome aberrations and micronuclei were evaluated to
      assess the induction of adaptive response to low dose ionizing radiation in each
      of the blood samples collected from eight different individuals. Following
      stimulation with phytohemagglutinin, the cells were exposed to an adaptive dose
      of 1 cGy X-radiation at 24 hours and a challenge dose of 150 cGy gamma radiation
      at 48 hours. Lymphocytes were fixed at 54 hours to examine the incidence of
      chromosome aberrations and at 72 hours to examine the frequency of micronuclei in
      cytokinesis-blocked binucleated cells. Lymphocytes from five donors, i.e.,
      "responders", exhibited the induction of adaptive response; their lymphocytes,
      which were pre-treated with 1 cGy had significantly fewer chromosome aberrations
      and micronuclei induced by the challenge dose of 150 cGy gamma radiation, as
      compared to the cells which did not receive the pre-treatment with 1 cGy. Such an
      induction of adaptive response was not observed in the remaining three donors,
      i.e., "non-responders"; the incidence of chromosome aberrations and micronuclei
      induced by the challenge dose of 150 cGy was not significantly different between
      the cells which were pre-exposed and un-exposed to 1 cGy. In all eight
      individuals, there was a strong positive correlation between the incidence of
      chromosome aberrations and micronuclei. Hence, whether or not an individual is a
      'responder' or 'non-responder' could be assessed using either chromosome
      aberrations or micronuclei as the end-point. The overall pattern of response
      confirms the heterogeneity in adaptive response between individuals to ionizing
      radiation, which may in part be genetically controlled. Because of the simplicity
      of the technique and rapid assessment of the binucleated cells, we suggest the
      use of the micronucleus test as an alternative procedure in large scale
      population studies related to the adaptive response.

PMID- 7565915
TI  - Salmonella and mammalian-cell mutagenicity of 3-chloro-4-(chloromethyl)-5-hydroxy
      2(5H)-furanone.
AB  - 3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF), a chlorine
      disinfection by-product in drinking water, was mutagenic in the Salmonella/his
      (Ames) assay for both base-pair substitution strains (TA1535, TA100, TA102) and
      frameshift strains (TA97, TA98) with the highest mutagenic response observed in
      strain TA100 (1292 revertants/microgram). The presence in TA100 of pKM101
      plasmid, which enhances error-phone DNA repair, greatly increased susceptibility
      to CMCF mutagenicity relative to the isogenic strain TA1535 lacking pKM101. In
      the Chinese hamster ovary (CHO) cell hprt (6-thioguanine resistance) locus assay,
      the mutagenicity of CMCF (1.04 mutants/10(6) clonable cells per microgram/ml) was
      barely detectable because of the low mutagenicity/cytotoxicity ratio. From the
      present experiments it appears that CMCF acts in a manner similar to that of
      another drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)
      furanone (MX). However, CMFC appears to be a less potent mutagen in vitro than
      MX.

PMID- 7565916
TI  - Enhanced cyto- and genotoxicity of tetracycline in Wilson disease fibroblasts.
AB  - Tetracycline (TC) exerts DNA damaging properties which are accelerated in the
      presence of copper(II). Thereby, reactive oxygen species are generated. We
      investigated, if copper-accumulating cells show a higher sensitivity to TC
      compared to normal cells. Fibroblasts with an increased copper content were
      derived from patients of two genetic disorders, Wilson disease (WD) and Menkes
      disease (MD). Cytotoxic and genotoxic effects of TC were investigated in
      different human fibroblasts. The inhibition of cell growth by TC was measured in
      two normal fibroblast lines, fibroblast lines of two patients with WD and one
      patient with MD. While TC inhibited cell growth at similar concentrations in
      normal fibroblasts and the MD fibroblasts, the WD cells were much more sensitive.
      Furthermore, an increased inhibition of DNA synthesis and an enhanced induction
      of unscheduled DNA synthesis (UDS) was found in WD cells after a TC-treatment
      compared to normal cells.

PMID- 7565917
TI  - A discussion of the ethical concept of futility.

PMID- 7565918
TI  - Decreased heart rate variability in amyotrophic lateral sclerosis.
AB  - Autoregressive spectral analysis of heart rate variability (HRV) was performed in
      29 patients with amyotrophic lateral sclerosis (ALS) and 33 age-matched healthy
      subjects to evaluate the involvement of the autonomic nervous system. HRV
      analysis provides a means to recognize low (LF) and high (HF) frequency
      components, respectively mediated by sympathetic and parasympathetic heart
      control. An increase in the mean heart rate at rest (P < 0.001), a decrease in
      standard deviation of R-R interval as well as in PNN50 (P < 0.001), and an
      increase in the LF/HF component ratio (P < 0.01) were found in the ALS patients,
      indicating a vagal-sympathetic imbalance. These alterations were not related to
      the clinical features and to the duration of the disease. Our results suggest a
      subclinical involvement of the autonomic nervous system in ALS, particularly
      affecting parasympathetic cardiovascular control.

PMID- 7565919
TI  - Immunolocalization of triadin, DHP receptors, and ryanodine receptors in adult
      and developing skeletal muscle of rats.
AB  - The dihydropyridine receptors (DHPR) and the ryanodine receptors (RyR) are well
      characterized proteins of the triad junctions of skeletal muscle fibers.
      Recently, a newly discovered 95-kDa protein, triadin, has been purified from
      rabbit skeletal muscle heavy sarcoplasmic reticulum (SR) vesicles. WE have used
      indirect immunogold EM to localize triadin to the junctional face of the SR in
      isolated triads. In addition, we have used indirect immunofluorescence to
      localize triadin in relation to the DHPR and the RyR in adult and developing rat
      skeletal muscle. In double immunolabelling experiments of longitudinally oriented
      adult rat skeletal muscle tissue, triadin-specific and RyR-specific antibodies
      resulted in a characteristic striated staining pattern. The staining arising from
      these antibodies completely overlapped when examined by computer analysis of
      digitized laser scanning confocal microscopy images. A similar result was
      obtained in double staining experiments using antibodies raised against the DHPR
      and the RyR suggesting that all three proteins are located in the triads in situ.
      The developmental expression of the three triad proteins was examined using
      double labeling of skeletal muscle tissue from several fetal and early postnatal
      ages. The staining patterns of triadin, RyR, and DHPR antibodies were overlapping
      throughout development, suggesting that from their earliest appearance the three
      proteins are components of the triads.

PMID- 7565920
TI  - The relation between conduction velocity and axonal length.
AB  - Motor evoked potentials (MEPs) obtained by electrical root stimulation and F
      waves were used to examine the proximal nerve conduction velocity (CV) to
      tibialis anterior (TA), extensor digitorum brevis (EDB), flexor carpi radialis
      (FCR), and abductor pollicis brevis (APB) muscles in 40 humans. By subtracting
      motor latencies obtained by stimulating the peripheral nerve at the same point
      from the F-wave and MEP latencies, we could measure the CV over identical
      proximal segments. It was found that proximal CV to TA and FCR was significantly
      higher than to EDB and APB, respectively. Combining the data of the proximal CV
      to all four muscles in relation with axonal length resulted in a highly
      significant inverse relationship (r2 = 0.77). Thus the axonal length explained to
      a large extent the higher CV of the arm nerves and also the inverse relation
      between body height and CV. The distal CV was always lower than proximal CV;
      however, there was no support for an additional effect of this gradient in
      explaining the relationship between CV and height since it was constant for all
      body heights.

PMID- 7565921
TI  - Effect of beta-endorphin on the contractile responses in mouse skeletal muscle.
AB  - Tension development in response to direct and indirect electrical stimulation was
      studied in an isolated phrenic nerve hemidiaphragm preparation of the mouse. beta
      Endorphin (beta-EP) caused an increase in the amplitude and a decrease in the
      time to peak of muscle contractions in response to low frequency stimulation of
      the nerve. Upon direct stimulation of the muscle the peptide had no effect. The
      actions of beta-EP were abolished in the presence of the opioid antagonist
      naloxone and mimicked by delta opioid agonists. Upon high frequency stimulation
      of the nerve, beta-EP caused an increase in the initial, maximum, and mean
      tension. It also prevented the fall in the final tension seen in the control
      preparations with repeated periods of stimulation. The findings are consistent
      with beta-EP having a role to improve neuromuscular function and delay fatigue,
      and indicate the possible therapeutic potential of opioid substances in
      conditions where muscle weakness is present.

PMID- 7565922
TI  - Conduction study of digital nerve function recovery following toe-to-digit
      transplantation and a comparison with digit-to-digit replantation.
AB  - Recovery of digital nerve function following toe-to-digit transplantation was
      studied by nerve conduction in 16 patients, and a comparison was made with digit
      to-digit replantation in 7 patients. For toe transplantation and digit
      replantation, the mean interval between injury and surgery was 7 months and 8 h,
      respectively, while the mean interval between surgery and study was 39 months and
      25 months, respectively. Sensory nerve action potentials (NAPs) from digital
      nerve stimulation were recorded at the wrist and the elbow, whereas mixed NAPs
      from median nerve stimulation at the wrist were recorded at the elbow. Sensory
      NAPs from stimulation of the transplanted toe were detectable in 14 patients and
      showed reduced amplitude, prolonged latency, and slowed conduction velocity.
      There was retrograde amplitude reduction in the median nerve and in the proximal
      segment of the digital nerve. Sensory NAPs from the replanted digit were not
      different from those of the normal digit, nor was a retrograde effect observed.
      The present data indicate that digital nerve function recovery was incomplete in
      toe transplantation and nearly complete in digit replantation. The reasons for
      the differences in recovery following two types of nerve repair are discussed.

PMID- 7565923
TI  - Superoxide dismutases of muscle in mitochondrial encephalomyopathies.
AB  - Immunohistochemical analyses were made of the superoxide dismutases (Mn-SOD and
      Cu/Zn-SOD) in biopsied muscles from 7 patients with mitochondrial
      encephalomyopathies that included mitochondrial encephalomyopathy, lactic
      acidosis and strokelike episodes (MELAS), and chronic progressive external
      ophthalmoplegia (CPEO). Mn-SOD mainly was present in the subsarcolemmal region,
      but it also was found in a coarsely granular, reticular, or diffuse pattern of
      staining within the muscle fibers. These Mn-SOD-positive fibers corresponded
      almost completely to the ragged-red fibers. The immunoreaction for Cu/Zn-SOD was
      weakly positive in some of the muscle fibers positive for Mn-SOD. In CPEO, Mn-SOD
      positive fibers predominantly showed decreased cytochrome c oxidase (COX)
      activity. In MELAS, Mn-SOD-positive fibers tended to be stained deeply for COX
      although a few were COX-negative. These findings suggest that Mn-SOD-positive
      fibers can be used to make a differential diagnosis between CPEO and MELAS and
      that in mitochondrial encephalomyopathies Mn-SOD in the ragged-red fibers may
      protect against oxidative stress.

PMID- 7565924
TI  - Comparison of digital sensory studies in patients with carpal tunnel syndrome.
AB  - Electrodiagnosis of carpal tunnel syndrome (CTS) often depends on the
      demonstration of focal slowing of median sensory fibers across the wrist. We
      compared the relative sensitivity of the four median innervated digits in
      demonstrating focal slowing in patients with CTS. Antidromic sensory studies of
      digits 1, 2, 3, and 4 were performed on 30 control subjects to develop normative
      data. Fifty-nine consecutive patients with CTS were then studied to determine the
      sensitivity of focal slowing of each median innervated digit. In the 26 CTS
      patients with a normal distal motor latency (DML) to abductor pollicis brevis,
      digit 1 was abnormal in 81%, digit 2 in 42%, digit 3 in 54%, and digit 4 in 38%.
      In the 33 CTS patients with a prolonged DML, digit 1 was abnormal in 94%, digit 2
      in 88%, digit 3 in 91%, and digit 4 in 88%. We conclude that in milder cases of
      CTS with a normal DML, digit 1 is the most sensitive in identifying focal slowing
      of sensory conduction across the wrist. However, in patients with a prolonged
      DML, the sensitivity of sensory conduction is not significantly different among
      the four digits.

PMID- 7565925
TI  - Immunocytochemical localization of vinculin in muscle and nerve.
AB  - A complete survey of the immunofluorescence distribution of the cytoskeletal
      protein vinculin in the normal skeletal muscle and peripheral nerve of humans and
      of different rodent species was performed. Our results enable us to localize
      vinculin in different types of adhesion plaques such as sarcolemmal costameres
      and neuromuscular and myotendinous junctions, but also in a fine
      intermyofibrillar lattice, possibly associated with intermediate filaments and/or
      with the triads. Moreover, we describe the presence of vinculin in junctional
      domains of several, previously unrecognized, specialized cells such as: the outer
      sheath of the muscle spindle capsule, the multilayered flat cells of the
      perineurium, the smooth muscle cells of epineurial blood vessels, and the
      endothelial cells in the endoneurium. These data call for a major role of
      vinculin in mechanisms of adhesion between cells, between cell and substrate and
      between intermyofibrillar components in the neuromuscular system. Such knowledge
      provides an anatomical background for studies on the possible pathological
      effects induced by an impairment in vinculin function.

PMID- 7565926
TI  - Facilitation of magnetic motor evoked potentials during the mixed nerve silent
      period.
AB  - We studied motor neuron excitability during the mixed nerve silent period (MNSP)
      in a hand muscle using magnetic motor evoked potentials (MEPs) and F-waves. MEPs
      elicited between the V1 and V2 potentials of the MNSP were much larger than
      control MEPs elicited at rest, and were even comparable in size to control MEPs
      elicited during voluntary contraction. This facilitation of MEPs occurred without
      shortening of MEP latency, suggesting a supraspinal mechanism. MEPs were
      facilitated during the MNSP when elicited with a figure-8-shaped coil in a
      posterior-anterior orientation, but not when MEPs of the same size were elicited
      with the coil held in a lateral-medial orientation. F-waves elicited during the
      MNSP were variable between subjects, and not consistently different from control
      F-waves elicited at rest. Our findings may reflect increased cortical motor
      excitability during the MNSP, possibly related to activation of muscle afferents
      by mixed nerve stimulation.

PMID- 7565928
TI  - Correlates of motor unit size, recruitment threshold, and H-reflex jitter.
AB  - The aim of this research was to study the neurophysiology of the anterior horn
      cell (AHC) using single-fiber EMG (SFEMG) study of the flexor carpi radialis
      (FCR) H-reflex. Twelve men and 7 women, ages 20-80 years, were studied. The mean
      H-jitter was 138 +/- 59 microseconds. H-jitter increased with age (while the M
      jitter did not) and was greater in men than in women. There was a direct
      correlation between the H-jitter and H-latency which was used as an indirect
      measure of the AHC's size. Given that small AHCs have a higher input resistance
      than large ones, the H-jitter can be used as an indirect indicator of the AHC's
      input resistance and therefore its size. When subjects fell asleep, the H-jitter
      increased over tenfold the baseline value, raising the possibility of an
      alternative, oligosynaptic pathway. H-reflex jitter studies provide a useful
      clinical neurophysiological tool for the study of AHC physiology.

PMID- 7565927
TI  - Comparison of contractile properties between developing and regenerating soleus
      muscle: influence of external calcium concentration upon the contractility.
AB  - In newborn rat skeletal extensor digitorum longus (EDL) muscle, it has been found
      that an influx of calcium from the extracellular medium is necessary for
      contraction, in contrast to the situation observed in adult EDL muscle. The aim
      of the present study was to determine the influence of the extracellular calcium
      concentration ([Ca]o) upon the contractile responses elicited in developing as
      well as in regenerating (notexin-injected) soleus (SOL) muscle. A morphological
      study was performed to follow the steps of postnatal development and regeneration
      in SOL muscle. In nominally calcium-free solution, the amplitudes of the twitch
      and tetanic tensions were greatly reduced in 1-14-day-old developing SOL muscles,
      as well as in notexin-injected SOL muscles. With longer times after birth, twitch
      and tetanic tensions of SOL muscle were less affected by the absence of calcium.
      This contrasts with notexin-injected SOL muscle in which the amplitudes of the
      contractions remained strongly dependent on [Ca]o. The present finding suggests
      that some functional characteristics are different in regenerating muscle fibers
      and may be of interest in the evaluation of the contractile properties of muscles
      in which injections of genetically engineered or not autologous myoblasts or
      viral vector have been performed.

PMID- 7565929
TI  - Desmin-related neuromuscular disorders.
AB  - Desmin, the intermediate filament protein of skeletal muscle fibers, cardiac
      myocytes, and certain smooth muscle cells, is a member of the cytoskeleton
      linking Z-bands with the plasmalemma and the nucleus. The pathology of desmin in
      human neuromuscular disorders is always marked by increased amounts, diffusely or
      focally. Desmin is highly expressed in immature muscle fibers, both during fetal
      life and regeneration as well as in certain congenital myopathies, together with
      vimentin. Desmin is also enriched in neonatal myotonic dystrophy and small fibers
      in infantile spinal muscular atrophy. Focal accretion of desmin may be twofold,
      in conjunction with certain inclusion bodies, cytoplasmic and spheroid bodies,
      and in a more patchy fashion, granulofilamentous material. Both lesions have been
      found in certain families, affected by a myopathy and/or cardiomyopathy. Other
      proteins, e.g., dystrophin, vimentin, actin, ubiquitin, and alpha-B crystallin,
      may also be overexpressed. Desmin pathology may be genetically regulated or may
      merely reflect profoundly impaired metabolism of several proteins within
      myofibers.

PMID- 7565930
TI  - Multiple mitochondrial DNA deletions in a patient with mitochondrial myopathy and
      cardiomyopathy but no ophthalmoplegia.
AB  - Deletions of muscle mitochondrial DNA are known in mitochondrial myopathy
      patients who have chronic progressive external ophthalmoplegia (CPEO). A 41-year
      old patient with no apparent family history of this condition suffers from
      hypertrophic cardiomyopathy, slight muscle atrophy, and weakness of the
      extremities, but not from CPEO. A muscle biopsy showed the presence of ragged-red
      fibers, and Southern blot analysis disclosed multiple deletions of muscle
      mitochondrial DNA. This combination of clinical features in our patient is
      atypical in mitochondrial myopathy with demonstrable deleted muscle mitochondrial
      DNA. Pleomorphic clinical expression is suggested.

PMID- 7565931
TI  - Sympathetic skin response (SSR) in the foot after sural nerve biopsy.

PMID- 7565932
TI  - Acute anterior interosseous neuropathy in a patient with hereditary neuropathy
      with liability to pressure palsies: a clinical and electromyographic study.

PMID- 7565933
TI  - Double anastomosis of median-ulnar and ulnar-median nerves: report of an
      electrophysiologically proven case.

PMID- 7565934
TI  - Does muscle reinnervation produce electromechanical dissociation in amyotrophic
      lateral sclerosis?

PMID- 7565935
TI  - Myasthenic symptoms in patients with mitochondrial myopathies.

PMID- 7565936
TI  - Role of ornithine decarboxylase in proliferation of Schwann cells during
      Wallerian degeneration and its enhancement by nerve expansion.

PMID- 7565937
TI  - Neuroprotective effect of cholinergic differentiation factor/leukemia inhibitory
      factor on wobbler murine motor neuron disease.

PMID- 7565938
TI  - The medial calcaneal nerve: anatomy and nerve conduction technique.

PMID- 7565939
TI  - Autoimmune thyroiditis and pulmonary fibrosis in a patient with myasthenia
      gravis.

PMID- 7565940
TI  - Long thoracic nerve palsy following cervical chiropractic manipulation.

PMID- 7565941
TI  - Bilateral anterior interosseus nerve syndrome.

PMID- 7565942
TI  - Further observations on all ulnar motor hand due to anomalous routing at the
      brachial plexus.

PMID- 7565943
TI  - Motor evoked potentials of the abdominal muscles elicited through magnetic
      transcranial brain stimulation.

PMID- 7565944
TI  - Pseudo-electrodiagnostic alert!

PMID- 7565945
TI  - Myasthenia gravis associated with dual infection of HIV and HTLV-I.

PMID- 7565946
TI  - Mutations of the growth hormone receptor in children with idiopathic short
      stature. The Growth Hormone Insensitivity Study Group.
AB  - BACKGROUND: Short stature in children who are not deficient in growth hormone
      (GH) is probably caused by a variety of defects. Some children with idiopathic
      short stature have low serum concentrations of GH-binding protein, which is
      derived from the GH receptor. The possibility that low serum concentrations of GH
      binding protein might indicate partial insensitivity to GH led us to investigate
      possible defects in the gene for the GH receptor in children with idiopathic
      short stature and low serum concentrations of GH-binding protein. METHODS: We
      studied 14 children with idiopathic short stature who were selected on the basis
      of normal GH secretion and low serum concentrations of GH-binding protein.
      Analysis of single-strand conformation polymorphisms and DNA sequencing were both
      used to identify mutations in the GH-receptor gene. RESULTS: Mutations in the
      region of the GH-receptor gene that codes for the extracellular domain of the
      receptor were found in 4 of the 14 children, but in none of 24 normal subjects.
      One of the four children with mutations was a compound heterozygote, with one
      mutation that reduced the affinity of the receptor for GH and a second mutation
      that may affect a function other than ligand binding. The remaining three
      children had single mutations in one allele of the gene. One mutation introduced
      a premature termination codon, and two caused substitutions of single amino acids
      in a structurally conserved domain of the receptor. CONCLUSIONS: Some children
      with idiopathic short stature may have partial insensitivity to GH due to
      mutations in the GH-receptor gene.

PMID- 7565947
TI  - Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational
      nucleoside analogue for chronic hepatitis B.
AB  - BACKGROUND: We describe severe and unexpected multisystem toxicity that occurred
      during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2
      fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic
      hepatitis B virus infection. METHODS: Fifteen patients with chronic hepatitis B
      were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg
      per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2
      weeks by means of a physical examination, blood tests, and testing for hepatitis
      B virus markers. RESULTS: During the 13th week lactic acidosis and liver failure
      suddenly developed in one patient. The study was terminated on an emergency
      basis, and all treatment with fialuridine was discontinued. Seven patients were
      found to have severe hepatotoxicity, with progressive lactic acidosis, worsening
      jaundice, and deteriorating hepatic synthetic function despite the
      discontinuation of fialuridine. Three other patients had mild hepatotoxicity.
      Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven
      patients with severe hepatotoxicity, five died and two survived after liver
      transplantation. Histologic analysis of liver tissue revealed marked accumulation
      of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or
      architectural changes. Electron microscopy showed abnormal mitochondria and the
      accumulation of fat in hepatocytes. CONCLUSIONS: In patients with chronic
      hepatitis B, treatment with fialuridine induced a severe toxic reaction
      characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and
      myopathy. This toxic reaction was probably caused by widespread mitochondrial
      damage and may occur infrequently with other nucleoside analogues.

PMID- 7565948
TI  - A comparison of five maintenance therapies for reflux esophagitis.
AB  - BACKGROUND: Patients with reflux esophagitis have a high rate of relapse within
      one year after therapy is discontinued. METHODS: We enrolled 175 adults with
      endoscopy-confirmed reflux esophagitis in a prospective study comparing five
      maintenance therapies. All the patients were initially treated with omeprazole
      (40 mg orally once a day) for four to eight weeks, and healing was confirmed by
      endoscopy. Participants were then stratified according to their initial grade of
      esophagitis and randomly assigned to 12 months of treatment with one of the
      following: cisapride (10 mg three times a day), ranitidine (150 mg three times a
      day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a
      day), or omeprazole plus cisapride. Endoscopy was repeated after 6 and 12 months
      of treatment; the endoscopists were blinded to the treatment assignments.
      Remission was defined as the absence of esophageal lesions on scheduled or
      unscheduled follow-up endoscopy. RESULTS: In an intention-to-treat analysis, the
      numbers of patients in continued remission at 12 months were 19 of 35 (54
      percent) in the cisapride group, 17 of 35 (49 percent) in the ranitidine group,
      28 of 35 (80 percent) in the omeprazole group, 23 of 35 (66 percent) in the
      ranitidine-plus-cisapride group, and 31 of 35 (89 percent) in the omeprazole-plus
      cisapride group. Omeprazole was significantly more effective than cisapride (P =
      0.02) or ranitidine (P = 0.003), and combination therapy with omeprazole plus
      cisapride was significantly more effective than cisapride alone (P = 0.003),
      ranitidine alone (P < 0.001), or ranitidine plus cisapride (P = 0.03). Ranitidine
      plus cisapride was significantly better than ranitidine alone (P = 0.05).
      CONCLUSIONS: For maintenance treatment of reflux esophagitis, omeprazole alone or
      in combination with cisapride is more effective than ranitidine alone or
      cisapride alone, and the combination of omeprazole and cisapride is more
      effective than ranitidine plus cisapride.

PMID- 7565949
TI  - Vascular tissue plasminogen activator and the development of coronary artery
      disease in heart-transplant recipients.
AB  - BACKGROUND: An aggressive and potentially fatal form of coronary artery disease
      may develop after cardiac transplantation. We studied the role of vascular tissue
      plasminogen activator (t-PA), the primary mediator of fibrinolysis, in the
      development of this problem. METHODS: We studied 78 consecutive recipients of
      cardiac allografts over a five-year period, and we collected follow-up data over
      a mean (+/- SE) of 32.5 +/- 2.0 months. The patients were studied with
      ventricular function tests, serial endomyocardial biopsies (16.6 +/- 0.5 per
      patient), and annual coronary angiography. Measurements of t-PA and its inhibitor
      were performed immunocytochemically on unfixed cryostat sections of
      endomyocardial-biopsy specimens with the use of monoclonal antibodies to t-PA and
      its inhibitor. RESULTS: In biopsy specimens obtained during the first three
      months of follow-up, 38 allografts had a normal distribution of t-PA in
      arteriolar smooth-muscle cells, whereas in 40 allografts there was depletion of t
      PA that persisted in subsequent follow-up. Coronary artery disease developed
      during follow-up in 31 of 40 allografts (78 percent) with depletion of t-PA, but
      the disease developed in only 9 of the 38 allografts (24 percent) with normal t
      PA levels (P < 0.001). Allografts with depletion of t-PA also had the t-PA
      inhibitor and were at greater risk for earlier and more severe disease than were
      allografts with normal arteriolar t-PA levels. Twelve patients whose allografts
      were depleted of t-PA either received a second transplant or died, whereas only
      one of the patients whose allografts had persistently normal t-PA levels died (P
      < 0.001). CONCLUSIONS: These findings reveal an association between the depletion
      of t-PA from arteriolar smooth-muscle cells and the subsequent development of
      coronary artery disease and decreased graft survival. Although we cannot be
      certain about a cause-and-effect relation, our data suggest a possible role for
      deficient fibrinolysis in the development of coronary artery disease in
      transplanted human hearts.

PMID- 7565950
TI  - Images in clinical medicine. Infarct cavities in a hepatic allograft.

PMID- 7565951
TI  - Drug-induced hepatotoxicity.

PMID- 7565952
TI  - Occupational illness.

PMID- 7565953
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 33-1995. Progressive neurologic deterioration with unusual
      findings on magnetic resonance imaging in a 43-year-old man treated for
      demyelinating disease.

PMID- 7565954
TI  - Broadening the growth hormone insensitivity syndrome.

PMID- 7565955
TI  - Mitochondrial toxicity--new adverse drug effects.

PMID- 7565956
TI  - Long-term therapy for reflux esophagitis.

PMID- 7565957
TI  - Otitis media in children.

PMID- 7565958
TI  - Otitis media in children.

PMID- 7565959
TI  - Otitis media in children.

PMID- 7565960
TI  - Fluoxetine for premenstrual dysphoria.

PMID- 7565961
TI  - Fluoxetine for premenstrual dysphoria.

PMID- 7565962
TI  - Transesophageal echocardiography.

PMID- 7565963
TI  - Hypoglycemic disorders.

PMID- 7565964
TI  - Hypoglycemic disorders.

PMID- 7565965
TI  - New neuromuscular blocking drugs.

PMID- 7565966
TI  - Recombinant granulocyte colony-stimulating factor in acute myelogenous leukemia.

PMID- 7565967
TI  - Topical nitroglycerin therapy for anal fissures and ulcers.

PMID- 7565968
TI  - Clinical problem-solving.

PMID- 7565969
TI  - Clinical problem-solving.

PMID- 7565970
TI  - The influence of smoking cessation on the prevalence of overweight in the United
      States.
AB  - BACKGROUND: The proportion of U.S. adults 35 to 74 years of age who were
      overweight increased by 9.6 percent for men and 8.0 percent for women between
      1978 and 1990. Since the prevalence of smoking declined over the same period,
      smoking cessation has been suggested as a factor contributing to the increasing
      prevalence of overweight. METHODS: To estimate the influence of smoking cessation
      on the increase in the prevalence of overweight, we analyzed data on current and
      past weight and smoking status for a national sample of 5247 adults 35 years of
      age or older who participated in the third National Health and Nutrition
      Examination Survey, conducted from 1988 through 1991. The results were adjusted
      for age, sociodemographic characteristics, level of physical activity, alcohol
      consumption, and (for women) parity. RESULTS: The weight gain over a 10-year
      period that was associated with the cessation of smoking (i.e., the gain among
      smokers who quit that was in excess of the gain among continuing smokers) was 4.4
      kg for men and 5.0 kg for women. Smokers who had quit within the past 10 years
      were significantly more likely than respondents who had never smoked to become
      overweight (odds ratios, 2.4 for men and 2.0 for women). For men, about a quarter
      (2.3 of 9.6 percentage points) and for women, about a sixth (1.3 of 8.0
      percentage points) of the increase in the prevalence of overweight could be
      attributed to smoking cessation within the past 10 years. CONCLUSIONS: Although
      its health benefits are undeniable, smoking cessation may nevertheless be
      associated with a small increase in the prevalence of overweight.

PMID- 7565972
TI  - Epidemic optic neuropathy in Cuba--clinical characterization and risk factors.
AB  - BACKGROUND: From 1991 to 1993, epidemic optic and peripheral neuropathy affected
      more than 50,000 people in Cuba. The number of new cases decreased after the
      initiation of vitamin supplementation in the population. In September 1993, Cuban
      and U.S. investigators conducted a study to characterize and identify risk
      factors for the optic form of the syndrome. METHODS: We conducted ophthalmologic
      and neurologic examinations, assessed exposure to potential toxins, administered
      a semiquantitative food-frequency questionnaire, and assessed serum measures of
      nutritional status in 123 patients with severe optic neuropathy, matched for sex
      and age to randomly chosen normal subjects. RESULTS: In the case patients,
      prominent clinical features were subacute loss of visual acuity with field
      defects, diminished color vision, optic-nerve pallor, and decreased sensitivity
      to vibration and temperature in the legs. Tobacco use, particularly cigar
      smoking, was associated with an increased risk of optic neuropathy. The risk was
      reduced among subjects with higher dietary intakes of methionine, vitamin B12,
      riboflavin, and niacin and higher serum concentrations of antioxidant
      carotenoids. The risk was also reduced among subjects who raised chickens at home
      or had relatives living overseas--factors that may be indirect measures of
      increased food availability. CONCLUSIONS: The epidemic of optic and peripheral
      neuropathy in Cuba between 1991 and 1993 appears to be linked to reduced nutrient
      intake caused by the country's deteriorating economic situation and the high
      prevalence of tobacco use.

PMID- 7565971
TI  - The genetic basis of the reduced expression of bilirubin UDP
      glucuronosyltransferase 1 in Gilbert's syndrome.
AB  - BACKGROUND: People with Gilbert's syndrome have mild, chronic unconjugated
      hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic
      glucuronidating activity, essential for efficient biliary excretion of bilirubin,
      is reduced to about 30 percent of normal. METHODS: We sequenced the coding and
      promoter regions of the gene for bilirubin UDP-glucuronosyltransferase 1
      (bilirubin/uridine diphosphoglucuronate-glucuronosyltransferase 1)--the only
      enzyme that contributes substantially to bilirubin glucuronidation--in 10
      unrelated patients with Gilbert's syndrome, 16 members of a kindred with a
      history of Crigler-Najjar syndrome type II, and 55 normal subjects. RESULTS: The
      coding region of the gene for the enzyme was normal in the 10 patients with
      Gilbert's syndrome. These patients were homozygous for two extra bases (TA) in
      the TATAA element of the 5' promoter region of the gene (A(TA)7TAA rather than
      the normal A(TA)6TAA). The presence of the longer TATAA element resulted in the
      reduced expression of a reporter gene, encoding firefly luciferase, in a human
      hepatoma cell line. The frequency of the abnormal allele was 40 percent among the
      normal subjects. The 3 men in the control group who were homozygous for the
      longer TATAA element had significantly higher serum bilirubin levels than the
      other 52 normal subjects (P = 0.009). Among the kindred with a history of Crigler
      Najjar syndrome type II, only the six heterozygous carriers who had a longer
      TATAA element on the structurally normal allele had mild hyperbilirubinemia,
      characteristic of Gilbert's syndrome. CONCLUSIONS: Reduced expression of
      bilirubin UDP-glucuronosyltransferase 1 due to an abnormality in the promoter
      region of the gene for this enzyme appears to be necessary for Gilbert's syndrome
      but not sufficient for the complete manifestation of the syndrome.

PMID- 7565973
TI  - Images in clinical medicine. Spur cells.

PMID- 7565974
TI  - A trial of annual in-home comprehensive geriatric assessments for elderly people
      living in the community.
AB  - BACKGROUND AND METHODS: The prevention of disability in elderly people poses a
      challenge for health care and social services. We conducted a three-year,
      randomized, controlled trial of the effect of annual in-home comprehensive
      geriatric assessment and follow-up for people living in the community who were 75
      years of age or older. The 215 people in the intervention group were seen at home
      by gerontologic nurse practitioners who, in collaboration with geriatricians,
      evaluated problems and risk factors for disability, gave specific
      recommendations, and provided health education. The 199 people in the control
      group received their regular medical care. The main outcome measures were the
      prevention of disability, defined as the need for assistance in performing the
      basic activities of daily living (bathing, dressing, feeding, grooming,
      transferring from bed to chair, and moving around inside the house) or the
      instrumental activities of daily living (e.g., cooking, handling finances and
      medication, housekeeping, and shopping), and the prevention of nursing home
      admissions. RESULTS: At three years, 20 people in the intervention group (12
      percent of 170 surviving participants) and 32 in the control group (22 percent of
      147 surviving participants) required assistance in performing the basic
      activities of daily living (adjusted odds ratio, 0.4; 95 percent confidence
      interval, 0.2 to 0.8; P = 0.02). The number of persons who were dependent on
      assistance in performing the instrumental activities of daily living but not the
      basic activities did not differ significantly between the two groups. Nine people
      in the intervention group (4 percent) and 20 in the control group (10 percent)
      were permanently admitted to nursing homes (P = 0.02). Acute care hospital
      admissions and short-term nursing home admissions did not differ significantly
      between the two groups. In the second and third years of the study, there were
      significantly more visits to physicians among the participants in the
      intervention group than among those in the control group (mean number of visits
      per month, 1.41 in year 2 and 1.27 in year 3 in the intervention group, as
      compared with 1.11 and 0.92 visits, respectively, in the control group; P = 0.007
      and P = 0.001, respectively). The cost of the intervention for each year of
      disability-free life gained was about $46,000. CONCLUSIONS: A program of in-home
      comprehensive geriatric assessments can delay the development of disability and
      reduce permanent nursing home stays among elderly people living at home.

PMID- 7565975
TI  - A multidisciplinary intervention to prevent the readmission of elderly patients
      with congestive heart failure.
AB  - BACKGROUND: Congestive heart failure is the most common indication for admission
      to the hospital among older adults. Behavioral factors, such as poor compliance
      with treatment, frequently contribute to exacerbations of heart failure, a fact
      suggesting that many admissions could be prevented. METHODS: We conducted a
      prospective, randomized trial of the effect of a nurse-directed,
      multidisciplinary intervention on rates of readmission within 90 days of hospital
      discharge, quality of life, and costs of care for high-risk patients 70 years of
      age or older who were hospitalized with congestive heart failure. The
      intervention consisted of comprehensive education of the patient and family, a
      prescribed diet, social-service consultation and planning for an early discharge,
      a review of medications, and intensive follow-up. RESULTS: Survival for 90 days
      without readmission, the primary outcome measure, was achieved in 91 of the 142
      patients in the treatment group, as compared with 75 of the 140 patients in the
      control group, who received conventional care (P = 0.09). There were 94
      readmissions in the control group and 53 in the treatment group (risk ratio,
      0.56; P = 0.02). The number of readmissions for heart failure was reduced by 56.2
      percent in the treatment group (54 vs. 24, P = 0.04), whereas the number of
      readmissions for other causes was reduced by 28.5 percent (40 vs. 29, P not
      significant). In the control group, 23 patients (16.4 percent) had more than one
      readmission, as compared with 9 patients (6.3 percent) in the treatment group
      (risk ratio, 0.39; P = 0.01). In a subgroup of 126 patients, quality-of-life
      scores at 90 days improved more from base line for patients in the treatment
      group (P = 0.001). Because of the reduction in hospital admissions, the overall
      cost of care was $460 less per patient in the treatment group. CONCLUSIONS: A
      nurse-directed, multidisciplinary intervention can improve quality of life and
      reduce hospital use and medical costs for elderly patients with congestive heart
      failure.

PMID- 7565976
TI  - Nicotine medications for smoking cessation.

PMID- 7565977
TI  - Gene therapy--a novel form of drug delivery.

PMID- 7565978
TI  - Clinical problem-solving. Testing, testing, testing....

PMID- 7565979
TI  - New hope for home care?

PMID- 7565980
TI  - The wrong way to stay slim.

PMID- 7565981
TI  - Gilbert's syndrome--a legitimate genetic anomaly?

PMID- 7565982
TI  - Managed care.

PMID- 7565983
TI  - Managed care.

PMID- 7565984
TI  - Managed care.

PMID- 7565985
TI  - Managed care.

PMID- 7565986
TI  - Managed care.

PMID- 7565987
TI  - Chronic pancreatitis.

PMID- 7565988
TI  - Managed care.

PMID- 7565989
TI  - Managed care.

PMID- 7565990
TI  - Chronic pancreatitis.

PMID- 7565991
TI  - Chronic pancreatitis.

PMID- 7565993
TI  - More on interferon-induced cutaneous necrosis.

PMID- 7565992
TI  - More on interferon-induced cutaneous necrosis.

PMID- 7565994
TI  - Outcomes after transfusion-associated hepatitis C.

PMID- 7565995
TI  - Discordant manifestations of hepatitis C in monozygotic twins.

PMID- 7565996
TI  - Nicotine addiction in young people.

PMID- 7565997
TI  - Nicotine addiction in young people.

PMID- 7565998
TI  - Survival after the age of 80 in the United States, Sweden, France, England, and
      Japan.
AB  - BACKGROUND: In many developed countries, life expectancy at birth is higher than
      in the United States. Newly available data permit, for the first time, reliable
      cross-national comparisons of mortality among persons 80 years of age or older.
      Such comparisons are important, because in many developed countries more than
      half of women and a third of men now die after the age of 80. METHODS: We used
      extinct-cohort methods to assess mortality in Japan, Sweden, France, and England
      (including Wales) and among U.S. whites for cohorts born from 1880 to 1894, and
      used cross-sectional data for the year 1987. Extinct-cohort methods rely on
      continuously collected data from death certificates and do not use the less
      reliable data from censuses. RESULTS: In the United States, life expectancy at
      the age of 80 and survival from the ages of 80 to 100 significantly exceeded life
      expectancy in Sweden, France, England, and Japan (P < 0.01). This finding was
      confirmed with accurate cross-sectional data for 1987. The average life
      expectancy in the United States is 9.1 years for 80-year-old white women and 7.0
      years for 80-year-old white men. CONCLUSIONS: For people 80 years old or older,
      life expectancy is greater in the United States than it is in Sweden, France,
      England, and Japan. This finding suggests that elderly Americans are receiving
      better health care than the elderly citizens of other developed countries.

PMID- 7565999
TI  - Postprandial versus preprandial blood glucose monitoring in women with
      gestational diabetes mellitus requiring insulin therapy.
AB  - BACKGROUND: The fetuses of women with gestational diabetes mellitus are at risk
      for macrosomia and its attendant complications. The best method of achieving
      euglycemia in these women and reducing morbidity in their infants is not known.
      We compared the efficacy of postprandial and preprandial monitoring in achieving
      glycemic control in women with gestational diabetes. METHODS: We studied 66 women
      with gestational diabetes mellitus who required insulin therapy at 30 weeks of
      gestation or earlier. The women were randomly assigned to have their diabetes
      managed according to the results of preprandial monitoring or postprandial
      monitoring (one hour after meals) of blood glucose concentrations. Both groups
      were also monitored with fasting blood glucose measurements. The goal of insulin
      therapy was a preprandial value of 60 to 105 mg per deciliter (3.3 to 5.9 mmol
      per liter) or a postprandial value of less than 140 mg per deciliter (7.8 mmol
      per liter). Obstetrical data and information on neonatal outcomes were collected.
      RESULTS: The prepregnancy weight, weight gain during pregnancy, gestational age
      at the diagnosis of diabetes and at delivery, degree of compliance with therapy,
      and degree of achievement of target blood glucose concentrations were similar in
      the two groups. The mean (+/- SD) change in the glycosylated hemoglobin value was
      greater in the group in which postprandial measurements were used (-3.0 +/- 2.2
      percent vs. 0.6 +/- 1.6 percent, P < 0.001) and the infants' birth weight was
      lower (3469 +/- 668 vs. 3848 +/- 434 g, P = 0.01). Similarly, the infants born to
      the women in the postprandial-monitoring group had a lower rate of neonatal
      hypoglycemia (3 percent vs. 21 percent, P = 0.05), were less often large for
      gestational age (12 percent vs. 42 percent, P = 0.01) and were less often
      delivered by cesarean section because of cephalopelvic disproportion (12 percent
      vs. 36 percent, P = 0.04) than those in the preprandial-monitoring group.
      CONCLUSIONS: Adjustment of insulin therapy in women with gestational diabetes
      according to the results of postprandial, rather than preprandial, blood glucose
      values improves glycemic control and decreases the risk of neonatal hypoglycemia,
      macrosomia, and cesarean delivery.

PMID- 7566000
TI  - Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein.
AB  - BACKGROUND: The epsilon 4 allele of apolipoprotein E has been associated with an
      increased risk of late-onset Alzheimer's disease. In a cohort of elderly subjects
      we prospectively investigated the relation between the apolipoprotein E genotype,
      dementia, and the accumulation of beta-amyloid protein in the cerebral cortex.
      METHODS: Autopsy involving neuropathological analysis and DNA analysis of frozen
      blood samples were performed in 92 of 271 persons who were at least 85 years of
      age, who had been living in Vantaa, Finland, on April 1, 1991, and who had died
      between that time and the end of 1993. All subjects had been tested for dementia.
      Apolipoprotein E genotyping was done with a solid-phase minisequencing technique.
      The percentage of the cortex occupied by methenamine silver-stained plaques was
      used as an estimate of the extent of beta-amyloid protein deposition. RESULTS:
      The frequency of the epsilon 4 allele was significantly higher in the subjects
      with Alzheimer's disease than in the subjects without dementia (30 percent vs. 8
      percent, P < 0.001). There was a greater accumulation of beta-amyloid protein in
      the brain and more neurofibrillary tangles in the subjects with the epsilon 4
      allele than in those without it (P < 0.001). The deposition of beta-amyloid
      protein varied according to the genotype in both the subjects with dementia and
      those without dementia: it was lowest in those with the epsilon 2/epsilon 3
      genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and
      highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the
      epsilon 4/epsilon 4 genotype and had dementia. CONCLUSIONS: The epsilon 4 allele
      of apolipoprotein E is significantly associated with Alzheimer's disease. Even in
      elderly subjects without dementia, the apolipoprotein E genotype is related to
      the degree of deposition of beta-amyloid protein in the cerebral cortex.

PMID- 7566001
TI  - Arterial oxygen saturation in Tibetan and Han infants born in Lhasa, Tibet.
AB  - BACKGROUND: Reduced oxygen availability at high altitude is associated with
      increased neonatal and infant mortality. We hypothesized that native Tibetan
      infants, whose ancestors have inhabited the Himalayan Plateau for approximately
      25,000 years, are better able to maintain adequate oxygenation at high altitude
      than Han infants, whose ancestors moved to Tibet from lowland areas of China
      after the Chinese military entered Tibet in 1951. METHODS: We compared arterial
      oxygen saturation, signs of hypoxemia, and other indexes of neonatal wellbeing at
      birth and during the first four months of life in 15 Tibetan infants and 15 Han
      infants at 3658 m above sea level in Lhasa, Tibet. The Han mothers had migrated
      from lowland China about two years previously. A pulse oximeter was placed on
      each infant's foot to provide measurements of arterial oxygen saturation distal
      to the ductus arteriosus. RESULTS: The two groups had similar gestational ages
      (about 38.9 weeks) and Apgar scores. The Han infants had lower birth weights
      (2773 +/- 92 g) than the Tibetan infants (3067 +/- 107 g), higher concentrations
      of cord-blood hemoglobin (18.6 +/- 0.8 g per deciliter, vs. 16.7 +/- 0.4 in the
      Tibetans), and higher hematocrit values (58.5 +/- 2.4 percent, vs. 51.4 +/- 1.2
      percent in the Tibetans). In both groups, arterial oxygen saturation was highest
      in the first two days after birth and was lower when the infants were asleep than
      when they were awake. Oxygen saturation values were lower in the Han than in the
      Tibetan infants at all times and under all conditions during all activities. The
      values declined in the Han infants from 92 +/- 3 percent while they were awake
      and 90 +/- 5 percent during quiet sleep at birth to 85 +/- 4 percent while awake
      and 76 +/- 5 percent during quiet sleep at four months of age. In the Tibetan
      infants, oxygen saturation values averaged 94 +/- 2 percent while they were awake
      and 94 +/- 3 percent during quiet sleep at birth and 88 +/- 2 percent while awake
      and 86 +/- 5 percent during quiet sleep at four months. Han infants had clinical
      signs of hypoxemia--such as cyanosis during sleep and while feeding--more
      frequently than Tibetans. CONCLUSIONS: In Lhasa, Tibet, we found that Tibetan
      newborns had higher arterial oxygen saturation at birth and during the first four
      months of life than Han newborns. Genetic adaptations may permit adequate
      oxygenation and confer resistance to the syndrome of pulmonary hypertension and
      right-heart failure (subacute infantile mountain sickness).

PMID- 7566002
TI  - Natural history of paroxysmal nocturnal hemoglobinuria.
AB  - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by
      intravascular hemolysis and venous thrombosis, is an acquired clonal disorder
      associated with a somatic mutation in a totipotent hematopoietic stem cell. An
      understanding of the natural history of PNH is essential to improve therapy.
      METHODS: We have followed a group of 80 consecutive patients with PNH who were
      referred to Hammersmith Hospital, London, between 1940 and 1970. They were
      treated with supportive measures, such as oral anticoagulant therapy after
      established thromboses, and transfusions. RESULTS: The median age of the patients
      at the time of diagnosis was 42 years (range, 16 to 75), and the median survival
      after diagnosis was 10 years, with 22 patients (28 percent) surviving for 25
      years. Sixty patients have died; 28 of the 48 patients for whom the cause of
      death is known died from either venous thrombosis or hemorrhage. Thirty-one
      patients (39 percent) had one or more episodes of venous thrombosis during their
      illness. Of the 35 patients who survived for 10 years or more, 12 had a
      spontaneous clinical recovery. No PNH-affected cells were found among the
      erythrocytes or neutrophils of the patients in prolonged remission, but a few PNH
      affected lymphocytes were detectable in three of the four patients tested.
      Leukemia did not develop in any of the patients. CONCLUSIONS: PNH is a chronic
      disorder that curtails life. A spontaneous long-term remission can occur, which
      must be taken into account when considering potentially dangerous treatments,
      such as bone marrow transplantation. Platelet transfusions should be given, as
      appropriate, and long-term anticoagulation therapy should be considered for all
      patients.

PMID- 7566003
TI  - Images in clinical medicine. Osmotic myelinolysis.

PMID- 7566004
TI  - Regulation of cell volume in health and disease.

PMID- 7566005
TI  - The management of cocaine-associated myocardial ischemia.

PMID- 7566006
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 34-1995. A 77-year-old woman with 17 years of gastrointestinal
      bleeding.

PMID- 7566007
TI  - Management of gestational diabetes mellitus.

PMID- 7566008
TI  - Molecular epidemiology of Alzheimer's disease.

PMID- 7566009
TI  - Interferon alfa and zidovudine in adult T-cell leukemia-lymphoma. Lymphoma Study
      Group of the Japan Clinical Oncology Group.

PMID- 7566010
TI  - Interferon alfa and zidovudine in adult T-cell leukemia-lymphoma.

PMID- 7566011
TI  - Childhood leukemias.

PMID- 7566012
TI  - Butyrate treatment in beta-hemoglobinopathies.

PMID- 7566013
TI  - Duration of anticoagulant therapy for venous thrombosis.

PMID- 7566014
TI  - Duration of anticoagulant therapy for venous thrombosis.

PMID- 7566015
TI  - Effect of a prior-authorization requirement on the use of nonsteroidal
      antiinflammatory drugs.

PMID- 7566016
TI  - Effect of a prior-authorization requirement on the use of nonsteroidal
      antiinflammatory drugs.

PMID- 7566017
TI  - Computer-based drug-utilization review.

PMID- 7566018
TI  - Declaring the sodium content of drug products.

PMID- 7566019
TI  - Medical care in Japan.

PMID- 7566020
TI  - Prevention of coronary heart disease with pravastatin in men with
      hypercholesterolemia. West of Scotland Coronary Prevention Study Group.
AB  - BACKGROUND: Lowering the blood cholesterol level may reduce the risk of coronary
      heart disease. This double-blind study was designed to determine whether the
      administration of pravastatin to men with hypercholesterolemia and no history of
      myocardial infarction reduced the combined incidence of nonfatal myocardial
      infarction and death from coronary heart disease. METHODS: We randomly assigned
      6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of
      272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin
      (40 mg each evening) or placebo. The average follow-up period was 4.9 years.
      Medical records, electrocardiographic recordings, and the national death registry
      were used to determine the clinical end points. RESULTS: Pravastatin lowered
      plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol
      levels by 26 percent, whereas there was no change with placebo. There were 248
      definite coronary events (specified as nonfatal myocardial infarction or death
      from coronary heart disease) in the placebo group, and 174 in the pravastatin
      group (relative reduction in risk with pravastatin, 31 percent; 95 percent
      confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions
      in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P
      < 0.001), death from coronary heart disease (definite cases alone: 28 percent
      reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P =
      0.042), and death from all cardiovascular causes (32 percent reduction, P =
      0.033). There was no excess of deaths from noncardiovascular causes in the
      pravastatin group. We observed a 22 percent reduction in the risk of death from
      any cause in the pravastatin group (95 percent confidence interval, 0 to 40
      percent; P = 0.051). CONCLUSIONS: Treatment with pravastatin significantly
      reduced the incidence of myocardial infarction and death from cardiovascular
      causes without adversely affecting the risk of death from noncardiovascular
      causes in men with moderate hypercholesterolemia and no history of myocardial
      infarction.

PMID- 7566021
TI  - Reduction of serum cholesterol with sitostanol-ester margarine in a mildly
      hypercholesterolemic population.
AB  - BACKGROUND: Dietary plant sterols, especially sitostanol, reduce serum
      cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more
      effective than a less soluble preparation. We tested the tolerability and
      cholesterol-lowering effect of margarine containing sitostanol ester in a
      population with mild hypercholesterolemia. METHODS: We conducted a one-year,
      randomized, double-blind study in 153 randomly selected subjects with mild
      hypercholesterolemia. Fifty-one consumed margarine without sitostanol ester (the
      control group), and 102 consumed margarine containing sitostanol ester (1.8 or
      2.6 g of sitostanol per day). RESULTS: The margarine containing sitostanol ester
      was well tolerated. The mean one-year reduction in serum cholesterol was 10.2
      percent in the sitostanol group, as compared with an increase of 0.1 percent in
      the control group. The difference in the change in serum cholesterol
      concentration between the two groups was -24 mg per deciliter (95 percent
      confidence interval, -17 to -32; P < 0.001). The respective reductions in low
      density lipoprotein (LDL) cholesterol were 14.1 percent in the sitostanol group
      and 1.1 percent in the control group. The difference in the change in LDL
      cholesterol concentration between the two groups was -21 mg per deciliter (95
      percent confidence interval, -14 to -29; P < 0.001). Neither serum triglyceride
      nor high-density lipoprotein cholesterol concentrations were affected by
      sitostanol. Serum campesterol, a dietary plant sterol whose levels reflect
      cholesterol absorption, was decreased by 36 percent in the sitostanol group, and
      the reduction was directly correlated with the reduction in total cholesterol (r
      = 0.57, P < 0.001). CONCLUSIONS: Substituting sitostanol-ester margarine for part
      of the daily fat intake in subjects with mild hypercholesterolemia was effective
      in lowering serum total cholesterol and LDL cholesterol.

PMID- 7566024
TI  - Images in clinical medicine. Cholesterol crystals.

PMID- 7566022
TI  - Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the
      alpha-tocopherol-transfer protein.
AB  - BACKGROUND: Patients with isolated vitamin E deficiency have an impaired ability
      to incorporate alpha-tocopherol into lipoproteins in the liver and usually have
      symptoms and signs of spinocerebellar dysfunction before adolescence. Accumulated
      evidence suggests that the alpha-tocopherol-transfer protein, which is presumed
      to function in the intracellular transport of alpha-tocopherol, is abnormal in
      these patients. METHODS: We studied a patient from an isolated Japanese island
      who began to have ataxia, dysarthria, and sensory disturbances in the sixth
      decade of life. His serum vitamin E concentration was low (1.2 micrograms per
      milliliter [2.8 mumol per liter]). Exons of his gene for the alpha-tocopherol
      transfer protein were analyzed by DNA sequencing. We also screened an additional
      801 inhabitants of the island for the mutation. Both the normal and mutant alpha
      to-copherol-transfer proteins were expressed in COS-7 cells and studied by
      immunoblot analysis and assay for alpha-tocopherol-transfer activity. RESULTS:
      The patient was homozygous for a point mutation that replaces histidine (CAT)
      with glutamine (CAG) at position 101 of the gene for the alpha-tocopherol
      transfer protein. When expressed in COS-7 cells, the missense mutation produced a
      functionally defective alpha-tocopherol-transfer protein with approximately 11
      percent of the transfer activity of the wild-type protein. Of the 801 island
      inhabitants examined, 21 were heterozygous for the His101Gln mutation. In all
      affected subjects, including the patient, this mutation cosegregated with an
      intron-sequence polymorphism. The heterozygotes were phenotypically normal and
      had serum vitamin E concentrations that were on average 25 percent lower than
      those of normal subjects (mean [+/- SD], 7.5 +/- 2.2 vs. 10.1 +/- 2.8 micrograms
      per milliliter [17.4 +/- 5.1 vs. 23.4 +/- 6.5 mumol per liter]; P = 0.002).
      CONCLUSIONS: alpha-Tocopherol-transfer protein is a determinant of serum vitamin
      E concentrations. An abnormality in this protein is a cause of spinocerebellar
      dysfunction.

PMID- 7566025
TI  - Effect of utilization review in a fee-for-service health insurance plan.
AB  - BACKGROUND: Although utilization review is widely used to control health care
      costs, its effect on patterns of health care is uncertain. METHODS: In 1989, New
      York City and its unions temporarily replaced actual utilization review with sham
      review for half the participants in the city's fee-for-service health insurance
      plan. We compared the health services provided to 3702 enrollees whose requests
      were subjected to utilization review (the review group) with the services
      provided to 3743 enrollees whose requests received sham review and were
      automatically approved for insurance coverage (the nonreview group). The
      enrollees, physicians, and hospitals were all unaware of the group assignments.
      RESULTS: During the study period (mean duration, eight months), the members of
      the review group underwent 1255 procedures in 20 categories of procedures for
      which second opinions were required (such as breast, cataract, foot, hernia, and
      hip-replacement surgery, as well as hysterectomy and coronary bypass surgery),
      and the members of the nonreview group underwent 1365 procedures (P = 0.02). The
      members of the review group had 124 fewer procedures in doctors' offices and
      hospital outpatient departments (P = 0.002). In the following year, the members
      of the review group underwent 248 procedures from the 20 categories, and the
      members of the nonreview group underwent 234 (P = 0.46). No other differences in
      patterns of care were found between the groups, including rates of hospital
      admission to medical-surgical, substances-abuse, or psychiatric units; average
      lengths of hospital stay; the percentage of enrollees who received preadmission
      testing; or rates of use of home care. During the study period, the mean age
      adjusted insurance payments per person were $7,355 in the review group and $6,858
      in the nonreview group (P = 0.06). CONCLUSIONS: The utilization-review program
      reduced the performance of diagnostic and surgical procedures for which second
      opinions were required and did not merely delay them until the following year.
      Otherwise, the program had little effect. Alternatively, actual review and sham
      review may both have decreased the use of hospital services, with patients or
      their physicians choosing more efficient treatment when they believed that care
      would be reviewed.

PMID- 7566026
TI  - Candidate AIDS vaccines.

PMID- 7566023
TI  - An epidemiologic study of Lyme disease in southern Sweden.
AB  - BACKGROUND: Lyme disease is the most common vector-borne infection in some
      temperate regions of the Northern Hemisphere. However, for most areas of endemic
      disease reliable epidemiologic data are sparse. METHODS: Over a one-year period,
      we conducted a prospective, population-based survey of cases of Lyme disease in
      southern Sweden. The diagnosis was made on the basis of the presence of erythema
      migrans at least 5 cm in diameter or characteristic clinical manifestations such
      as arthritis, neuroborreliosis, and carditis. RESULTS: We identified 1471
      patients with Lyme disease, for an overall annual incidence of 69 cases per
      100,000 inhabitants. The incidence varied markedly according to geographic
      region, and there were several areas where disease was widely prevalent. The
      incidence varied according to age, with the highest rates among people 5 to 9 and
      60 to 74 years of age, but not according to sex. The most frequent clinical
      manifestation was erythema migrans (seen in 77 percent of all cases), followed by
      neuroborreliosis (16 percent) and arthritis (7 percent). Carditis was rare. A
      preceding tick bite was reported by 79 percent of the patients. Bites in the head
      and neck region were more common among children than among adults and were
      associated with an increased risk of neuroborreliosis. CONCLUSIONS: Lyme disease
      is very common in southern Sweden, with a relatively high frequency of neurologic
      complications and arthritis. With the exception of the low incidence of carditis,
      the pattern of disease we found in Sweden was similar to that reported in the
      United States.

PMID- 7566027
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 35-1995. A 55-year-old disabled construction worker with
      increasing dyspnea and abnormal chest radiographs.

PMID- 7566029
TI  - Lowering cholesterol with drugs and diet.

PMID- 7566028
TI  - Our ailing public hospitals. Cure them or close them?

PMID- 7566031
TI  - Rethinking utilization review.

PMID- 7566030
TI  - Spinocerebellar ataxias and ataxins.

PMID- 7566032
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566033
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566034
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566036
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566035
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566037
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566038
TI  - Breast cancer and hormone-replacement therapy.

PMID- 7566039
TI  - Lactose intolerance.

PMID- 7566040
TI  - Lactose intolerance.

PMID- 7566041
TI  - Lactose intolerance.

PMID- 7566042
TI  - Lactose intolerance.

PMID- 7566043
TI  - Doxorubicin-induced cardiotoxicity.

PMID- 7566044
TI  - Doxorubicin-induced cardiotoxicity.

PMID- 7566045
TI  - Lactobacilli to prevent traveler's diarrhea?

PMID- 7566046
TI  - Mass fainting at medieval rock concerts.

PMID- 7566048
TI  - Morphological differentiation of Fusarium sambucinum Fuckel sensu stricto, F.
      torulosum (Berk. & Curt.) Nirenberg comb. nov. and F. venenatum Nirenberg sp.
      nov.
AB  - Within Fusarium sambucinum Fuckel sensu lato three species were differentiated:
      F. sambucinum Fuckel s. str., F. torulosum (Berk. et Curt.) Nirenberg comb. nov.
      and F. venenatum Nirenberg sp. nov. They are described and illustrated in detail.

PMID- 7566049
TI  - Computer-aided morphometrical analysis of macroconidia in Fusarium sambucinum
      Fuckel sensu lato strains.
AB  - Forty-one strains of Fusarium sambucinum Fuckel sensu lato were classified on the
      basis of morphological data of the macroconidia obtained by automated microscopic
      image analysis. The classification factors were determined in six Fusarium
      strains of the section Discolor. The results show the relative homogeneity within
      the groups proposed by Nirenberg. A remarkable difference could be detected
      especially between the groups F. sambucinum, F. torulosum and F. sambucinum sensu
      lato on the one hand and F. spec nov. on the other.

PMID- 7566047
TI  - Introduction. The European Fusarium Sambucinum Project.

PMID- 7566050
TI  - Sexual fertility of forty Fusarium strains from the European Fusarium sambucinum
      project.
AB  - Fungus strains designated as Fusarium sambucinum, F. torulosum, or Fusarium sp.
      nov. were crossed with MAT1-1 and MAT1-2 tester strains of Gibberella pulicaris.
      Of the 40 field strains that were crossed with the tester strains, 13 strains
      produced fertile crosses and 27 strains did not produce fertile crosses. One
      strain designated as F. torulosum was fertile with a tester strain of G.
      pulicaris, suggesting that this is an intraspecies cross and that the strain is
      G. pulicaris, and, consequently, F. sambucinum rather than F. torulosum. The lack
      of fertile crosses between tester strains and 27 of the 40 field strains suggests
      that these strains are not G. pulicaris. Although the ability to form a fully
      fertile cross with a tester strain can determine the species of a fertile strain,
      it is more problematic to exclude a strain only because it is infertile.

PMID- 7566051
TI  - Phylogenetic relationship within Fusarium sambucinum Fuckel sensu lato,
      determined from ribosomal RNA sequences.
AB  - Partial ribosomal RNA nucleotide sequences were determined for 11 strains of
      Fusarium sambucinum Fuckel sensu lato to assess by molecular genetic means,
      Nirenberg's recent morphotaxonomic interpretation which split the species into
      three distinct taxa: F. sambucinum sensu stricto, F. torulosum, and one other
      species, as yet unnamed (Fusarium species nova). Four sequence patterns were
      identified among the 11 strains. Two sequences that varied at one site were found
      among strains of F. sambucinum, strains of F. torulosum and Fusarium sp. nov.
      showed no intraspecific variation. Interspecific comparisons revealed nucleotide
      sequence differences of 3-9 substitutions in the ca. 240 nucleotide rRNA segment
      examined. Although interspecific differences are not large in terms of percent
      nucleotide substitution, they are much larger than the observed intraspecific
      variation and support the morphological interpretation distinguishing three taxa.
      When the data were analysed using parsimony and bootstrapping, the three taxon
      tree was well supported. The phylogenetic arrangement of these strains is
      congruent with secondary metabolite profile similarities.

PMID- 7566052
TI  - Differentiation of Fusarium sambucinum Fuckel sensu lato and related species by
      RAPD PCR.
AB  - DNA polymorphisms generated by the random amplified polymorphic DNA polymerase
      chain reaction (RAPD PCR) were used to analyse 41 isolates investigated in the
      European Fusarium sambucinum Project (EFSP). Employing ten arbitrary (10-mer)
      oigonucleotides and simple repeat sequences (M13, (GACA)4) as single primers,
      informative banding patterns typical for identifying European populations of
      Fusarium sambucinum Fuckel s. str., F. torulosum (Berk. & Curt.) Nirenberg and F.
      venenatum Nirenberg were obtained.

PMID- 7566053
TI  - Analysis of esterase zymograms of Fusarium sambucinum and related species.
AB  - Esterase zymograms were obtained following polyacrylamide slab gel
      electrophoresis of protein extracts Fusarium sambucinum and related species
      originating from different geographic locations and different matrices. The sites
      of esterase activity were recorded, and the Rfs were calculated. The data were
      used for the construction of phenograms by cluster analysis and nonlinear mapping
      by computerized classification techniques. The fifteen isolates of F. sambucinum,
      the eight isolates of F. torulosum and the six isolates of F. spec. nov. each had
      identical profiles, and are therefore electrophoretically distinct species. The
      isolates of F. sarcochroum, one of F. sambucinum sensu lato (BBA 64280) and
      fifteen isolates of F. sambucinum were electrophoretically indistinguishable from
      each other. We assume they are synonymous. The isolate of F. bacteridiodes, one
      of F. sambucinum sensu lato (BBA 64993) and eight isolates of F. torulosum had
      uniform EST patterns, therefore the two species are electrophoretically
      identical. We assume they are also synonymous. The remaining three isolates of F.
      sambucinum sensu lato are somewhat closely related to F. sambucinum isolates on
      the basis of our investigations.

PMID- 7566054
TI  - Toxicity of Fusarium sambucinum Fuckel sensu lato to brine shrimp.
AB  - In a screening test seven Fusarium strains out of 17 proved to be toxic towards
      brine shrimp. Among these, four F. sambucinum strains as well as three F.
      venenatum isolates caused toxic effects. The chemical screening by TLC analysis
      revealed the presence of sambucinol and diacetoxyscirpenol in the extracts of the
      toxic isolates of F. venenatum 64537.

PMID- 7566055
TI  - Production of type A trichothecenes and enniatin B by Fusarium sambucinum Fuckel
      sensu lato.
AB  - Twenty-nine Fusarium isolates, representing three new taxa originated by
      Nirenberg from F. sambucinum Fuckel sensu lato, namely: F. sambucinum Fuckel
      sensu stricto, F. venenotum Nirenb., and F. torulosum (Berk. & Curt.) Nirenb.,
      were tested for in vitro production of toxic secondary metabolites on autoclaved
      corn kernels. F. sambucinum sensu stricto was able to produce type A
      trichothecenes and enniatin B (EB). In particular, amongst the 14 isolates
      tested, 5 produced only diacetoxyscirpenol (DAS) (up to 700 micrograms/g); 1
      produced only neosolaniol (NEOS) (250 micrograms/g); 2 produced T-2 toxin (T-2) +
      NEOS (up to 175 and 150 micrograms/g, respectively); 1 produced NEOS + DAS (300
      and 100 micrograms/g, respectively); and 5 produced DAS + EB (up to 500 and 140
      micrograms/g, respectively). All six isolates of F. venenotum were able to
      produce only DAS (up to 100 micrograms/g). F. torulosum produced no
      trichothecenes, but four out of nine tested isolates were able to produce EB (up
      to 140 micrograms/g). Zearalenones and type B trichothecenes were not found. The
      toxicity of the culture extracts towards Artemia salina L. was correlated in
      general with the occurrence of the above toxins, except for some F. torulosum
      strains. However, the lack of correlation between the amounts of toxins recovered
      and toxic activity observed in the Geotrichum candidum Link ex Pers. and A.
      salina assays suggested the presence of unknown toxic compounds.

PMID- 7566056
TI  - Chemical and physiological characterization of taxa in the Fusarium sambucinum
      complex.
AB  - Forty-one isolates of Fusarium sambucinum sensu lato were screened for production
      of secondary metabolites in agar cultures. Of 16 strains of F. sambucinum sensu
      stricto all but two strains produced diacetoxyscirpenol and two unidentified
      metabolites, TB1 and TB2 respectively. The two remaining F. sambucinum strains
      produced T-2 toxin, TB1 and TB2. Fusarium venenotum (6 strains) produced
      diacetoxyscirpenol and an unidentified metabolite BB. Fusarium torulosum (8
      strains) produced wortmannin and antibiotic Y. The three species could be
      differentiated by their pattern of identified and unidentified metabolites
      detected by agar plug TLC combined with chemical data from HPLC-diode array
      detection of fungal extracts, and data on growth rates on potato sucrose agar and
      tannin sucrose agar.

PMID- 7566057
TI  - Studies on fungi associated with tomato fruits and effectiveness of some
      commercial fungicides against three pathogens.
AB  - Among 39 fungal species and one variety belonging to 16 genera isolated from 116
      healthy tomato fruits collected from markets in Assiut, Egypt, during 1994,
      Aspergillus niger was found to be the most prevalent, being isolated from 84.6%
      of the samples. Of 11 species recovered from 156 diseased tomatoes, Alternaria
      alternata, Rhizopus stolonifer and A. niger were the most common and isolated
      from 52.7%, 35.9% and 25.0% of the samples, respectively. Experiments for
      comparison of the effects of medium containing tomato juice with synthetic medium
      on the mycelial growth of nine fungal species indicated that, the tomato juice
      medium was more suitable for growth of all fungal species. The effect of five
      commercial fungicides and sodium hypochlorite when applied as post-harvest dips
      after inoculation was studied in laboratory against A. alternata, A. niger and R.
      stolonifer. At 10 and 100 micrograms ml-1, neither of the fungicide caused a
      noticeable inhibition of Alternaria rot. At 1000 micrograms ml-1 benlate, rovral
      and sumisclex completely prevented Alternaria and Aspergillus rot, whereas
      cuprosan and ridomil were ineffective against rotting caused by A. niger.
      Rhizopus rot development was inhibited by over 50% with one treatment only
      (rovral at 1000 micrograms ml-1). Sodium hypochlorite has good curative
      properties against fruit rots especially those caused by A. alternata and A.
      niger.

PMID- 7566058
TI  - Production of fumonisins by Fusarium species of Taiwan.
AB  - Twenty-nine Fusarium species isolated from various sources in different districts
      of Taiwan were tested for their ability to produce fumonisins in corn cultures.
      Only Fusarium moniliforme produced fumonisin B1 (FB1) and fumonisin B2 (FB2). The
      finding that the other 28 Fusarium species produced neither FB1 nor FB2 is
      preliminary because only one strain per species was studied. The detection of FB1
      and FB2 in cultures of F. moniliforme was demonstrated by TLC and HPLC, and FB1
      was further confirmed by mass spectrometry. In a separate experiment, in which 38
      strains of F. moniliforme were tested for fumonisins, approximately 66% (25/38)
      produced FB1 and/or FB2. Of the 25 strains, 14 produced only FB1 and 11 produced
      both FB1 and FB2, and the amounts of FB1 and FB2 produced by different strains
      varied greatly. This is the first report that fumonisins are found in corn
      cultures experimentally infected with F. moniliforme strains from Taiwan. It is
      safe to assume that fumonisin producing strains of F. moniliforme are widely
      distributed among the economic crops such as corn, rice, sugarcane, and sorghum
      throughout the Island.

PMID- 7566059
TI  - Fungal diseases of fish in Nanak Sagar, Naini Tal, India.
AB  - Eight zoosporic fungi viz., Achlya debaryana, A. flagellata, A. klebsiana,
      Aphanomyces laevis, Saprolegnia diclina, S. ferax, S. parasitica, and Pythium sp.
      were isolated from a large number of adult fishes of the species Mastacembelus
      armatus, Mystus vitatus, Nandus nandus, Tor putitora and T. tor of Nanak Sagar
      reservoir in Naini Tal district, India. Species of the parasites and the hosts
      were different in their pathogenicity and immunity, respectively. However, A.
      flagellata and S. parasitica appeared to be the most virulent. The severity of
      mycosis was primarily correlated to moderate water temperatures of 22-25 degrees
      C. High temperature (> 28 degrees C) retarded the disease process. The
      experimental inoculation with all the associated fungal species on Puntius
      conchonius in the laboratory produced clinical signs similar to the ones seen on
      infected fish in the reservoir. This is the first report on fish mycosis in the
      large reservoir located in the foot hill of Kumaun Himalaya.

PMID- 7566060
TI  - Polyserositis in a patient with acute paracoccidioidomycosis and hepatosplenic
      schistosomiasis.
AB  - A severe case of juvenile paracoccidioidomycosis (PCM), manifested as cholestatic
      jaundice, lymph node enlargement and an unusual form of polyserositis, associated
      with portal hypertension secondary to schistosomiasis, as well as bacteremias
      caused by E. coli and S. aureus and post-transfusional hepatitis C is reported.
      Temporary unresponsiveness of in vivo and in vitro cellular immune responses to
      P. brasiliensis were registered. The authors discuss the possible interference of
      either agent in the host immune response, thus explaining the severity of PCM in
      the present case.

PMID- 7566061
TI  - Fungi inhabiting household environments in Riyadh, Saudi Arabia.
AB  - Fungi inhabiting household environments in the West, East and Central localities
      of Riyadh city were screened. The screened area included bedrooms, drawing rooms,
      living rooms, kitchens and bathrooms. The common genera of fungi isolated were
      Alternaria, Aspergillus, Cercospora, Chaetomium, Cladosporium, Curvularia,
      Drechslera, Embellisia, Fusarium, Mucor, Penicillium, Rhizopus, Scytalidium,
      Trichoderma, Torula and Ulocladium. Two uncommon genera Nodulosporium and
      Oidiodendron for Saudi Arabian mycoflora were also isolated. In all the
      localities, the highest number of fungal colonies per plate or per gram were
      found in the living rooms, followed by bedrooms. The number of colonies per plate
      or per gram was in general higher in densely populated than in less populated
      areas.

PMID- 7566062
TI  - Cutaneous zygomycosis caused by Absidia corymbifera in a leukemic patient.
AB  - A case of cutaneous zygomycosis caused by Absidia corymbifera in a leukemic
      patient submitted to chemotherapy is reported. The lesion was located on the
      little finger of the right hand and probably resulted from a latent
      osteomyelitis. It progressed to form extensive necrotic area. No systemic
      infection was detected and the lesion did not appear to be associated with any
      trauma.

PMID- 7566063
TI  - Simple new test for rapid differentiation of Prototheca stagnora from P.
      wickerhamii and P. zopfii.
AB  - A simple new test to differentiate Prototheca wickerhamii and P. zopfii from P.
      stagnora by determining susceptibility to neomycin is described. Susceptibility
      determined using a 30 micrograms neomycin disk provides a rapid and reliable
      means of distinguishing P. wickerhamii and P. zopfii from P. stagnora.

PMID- 7566064
TI  - Effect of proteolytic and glycolytic enzymes on a factor in Sorghum bicolor that
      induces mycelial growth in the smut fungus, Sporisorium reilianum.
AB  - Proteins obtained from seedling shoots and floral meristems of Sorghum bicolor
      (L.) Moench cv. NK 1210 induced mycelial growth in the smut fungus, Sporisorium
      reilianum in vitro. Proteins precipitated with trichloroacetic acid and ammonium
      sulfate were equally effective as inducers, although there were minor variations
      in the pattern of mycelial growth. Hydrolysis of the protein fraction with the
      proteolytic enzyme pronase E resulted in considerable reduction in the proteins'
      ability to induce mycelial growth. Digestion of the protein fraction with
      driselase, resulted in a slight enhancement of biological activity. The results
      suggest that amino sugar moieties in glycoproteins may act as inducers of
      mycelial growth in Sporisorium reilianum.

PMID- 7566065
TI  - The changing spectrum of medical mycology education or a medical mycologist who
      can't swim will sink in a hurry.

PMID- 7566067
TI  - Efficacy of 6-amino-2-n-pentylthiobenzothiazole on Trichophyton in vitro and in
      vivo.
AB  - In vitro and in vivo antifungal activities of synthetically parepared 6-amino-2-n
      pentylthiobenzothiazole (APB) against Trichophyton strains were studied. APB
      inhibited the growth of 3 Trichophyton strains at 65 micrograms/ml. 2
      Mercaptobenzothiazole was not effective at 125 micrograms/ml and ketoconazole
      inhibited the growth at 20-30 micrograms/ml. Treatment of experimental
      dermatophytosis in guinea pigs using 2.5% APB cream was studied in comparison to
      Canesten cream (1% clotrimazole). Dermatophytosis was considerably reduced after
      both APB and Canesten therapies.

PMID- 7566068
TI  - Cryptococcal prostatitis in a patient with Behcet's disease treated with
      fluconazole.
AB  - A 55-year-old man with Behcet's disease presented acute urinary retention due to
      Cryptococcus neoformans infection of the prostate. The disease was localized to
      the prostate. The infection was successfully treated only with fluconazole. The
      patient remains well without evidence of systemic or local infection at 32
      months.

PMID- 7566069
TI  - A report on the predominant occurrence of a dermatophyte species in cultivated
      soil from Kuwait.
AB  - From several soil samples screened for the occurrence of keratinolytic fungi,
      soils cultivated with ornamental plants were found to contain strains of the
      dermatophytic fungus Microsporum gypseum. One soil sample was dominated by this
      species.

PMID- 7566066
TI  - Effect of macrophage blockade on the resistance of inbred mice to
      Paracoccidioides brasiliensis infection.
AB  - The effect of macrophage blockade on the natural resistance and on the adaptative
      immune response of susceptible (B10.D2/oSn) and resistant (A/Sn) mice to
      Paracoccidioides brasiliensis infection was investigated. B10.D2/oSn and A/Sn
      mice previously injected with colloidal carbon were infected ip with yeast cells
      to determine the 50% lethal dose, and to evaluate the anatomy and histopathology,
      macrophage activation, antibody production and DTH reactions. Macrophage blockade
      rendered both resistant and susceptible mice considerably more susceptible to
      infection, as evidenced by increased mortality and many disseminated lesions. P.
      brasiliensis infection and/or carbon treatment increased the ability of
      macrophages from resistant mice to spread up to 25 days after treatment. In
      susceptible mice the enhanced spreading capacity induced by carbon treatment was
      impaired at all assayed periods except at 1 week after infection. Macrophage
      blockade enhanced DTH reactions in resistant mice, but did not alter these
      reactions in susceptible mice, which remained anergic. To the contrary,
      macrophage blockade enhanced specific antibody production by susceptible mice,
      but did not affect the low levels produced by resistant mice. The effect of
      macrophage blockade confirms the natural tendency of resistant animals to mount
      DTH reactions in the course of the disease and the preferential antibody response
      developed by susceptible mice after P. brasiliensis infection. On the whole,
      macrophage functions appear to play a fundamental role in the natural and
      acquired resistance mechanisms to P. brasiliensis infection.

PMID- 7566072
TI  - When is genetic screening permissible?

PMID- 7566071
TI  - Production of neosolaniol by Fusarium tumidum.
AB  - Extracts from autoclaved maize culture of Fusarium tumidum strain R-5823 were
      toxic towards Artemia salina. Bioassay-guided fractionation of the organic
      extract led to the isolation of the toxic compound that was identified as the
      trichothecene toxin neosolaniol (NEOS) by 1H, 13C nuclear magnetic resonance
      spectroscopy and low-resolution electronic impact mass spectrometry. The amount
      of NEOS produced by the strain R-5823 was 300 mg/kg maize culture. NEOS was also
      detected by HPLC in cultures of four out of seven additional strains of F.
      tumidum and Gibberella tumida with different origin, in amounts ranging from 1 to
      311 mg/kg. This is the first report on the production of a trichothecene toxin by
      F. tumidum.

PMID- 7566073
TI  - Crime and genetics conference breeds further controversy.

PMID- 7566070
TI  - Fumonisin B1 alters sphingolipid metabolism and immune function in BALB/c mice:
      immunological responses to fumonisin B1.
AB  - Fumonisins have been reported to have diverse effects on animals, including
      immunosuppression in chickens and feeder calves; therefore, the effects of
      fumonisin B1 (FB1) on immune function in BALB/c mice was investigated. When
      administered i.p. with sheep red blood cells (SRBC), 5 to 100 micrograms of FB1
      reduced the number of plaque-forming cells (PFC) produced against SRBC; however,
      when administered daily, 1 to 50 micrograms of FB1 caused a 4 to 12-fold increase
      in the number of PFC after SRBC injection. Therefore, FB1 is not only
      immunosuppressive; but also, immunostimulatory. To test the possibility that
      there may have been an immune response to FB1 as an antigen, FB1 was injected
      into mice and the number of splenic cells forming rosettes on FB1-treated SRBC
      was determined. There were dose-dependent increases in the antigen-binding cells,
      with up to 4.9- and 4.6-fold increases, respectively, upon primary and secondary
      immunization. FB1-binding immunoglobulins could be detected in sera from some
      treated mice, but this response was not obtained in every experiment. In summary,
      these results show that FB1 has diverse effects on the immune system, causing
      both stimulation and suppression of the response to foreign antigens, and
      apparently inducing an antigenic response to FB1.

PMID- 7566074
TI  - AZT combination trial shows positive results.

PMID- 7566076
TI  - Forensic team digs up Haiti's deadly past.

PMID- 7566075
TI  - Spermatid injection fertilizes ethics debate.

PMID- 7566077
TI  - Physicians prepare guidelines on use of human genome data.

PMID- 7566078
TI  - ORI's unhappy lot.

PMID- 7566080
TI  - A big book of the human genome. Navigational progress.

PMID- 7566079
TI  - A big book of the human genome. Complementary endeavours.

PMID- 7566081
TI  - Signal transduction. Notch takes a short cut.

PMID- 7566082
TI  - Blindsight in real sight.

PMID- 7566083
TI  - Cortical areas in visual awareness.

PMID- 7566084
TI  - The amygdala and emotional memory.

PMID- 7566085
TI  - A base pair between tRNA and 23S rRNA in the peptidyl transferase centre of the
      ribosome.
AB  - Interaction of the conserved CCA terminus of tRNA with rRNA in the peptidyl
      transferase P site has been studied by in vitro genetics. A watson-Crick G-C pair
      between G2252 in a conserved hairpin loop of 23S rRNA and C74 at the acceptor end
      of tRNA is required for proper functional interaction of the CCA end of tRNA with
      the ribosomal P site. These findings establish a direct role for 23S rRNA in
      protein synthesis.

PMID- 7566086
TI  - Blindsight in normal observers.
AB  - Some patients with lesions in visual cortex lack conscious visual experience but,
      when tested, exhibit a significant ability, termed 'blindsight', to discriminate
      visual stimuli. Here we report two different visual displays that induce
      blindsight in normal observers. Using an objective measure, we show that
      conscious experience remains defective at presentation times much longer (1 s)
      than the onset of visual sensitivity (approximately 60 ms). To obtain this
      effect, we generate a contrast between visual textures and then conceal the
      contrast by superimposing 'complementary' textures. Complementarity can involve
      either opposite motion or binocular rivalry and orthogonal orientation. In both
      cases, observers locate the texture contrast reliably but do not, by either
      subjective or objective measures, consciously experience it. Taken together with
      present knowledge of the visual cortical site(s) at which opposite motion and
      rivalrous orientation interact, this observation bears upon the functional
      anatomy of conscious visual experience.

PMID- 7566087
TI  - Which parts of the road guide steering?
AB  - A driver steering a car on a twisting road has two distinct tasks: to match the
      road curvature, and to keep a proper distance from the lane edges. Both are
      achieved by turning the steering wheel, but it is not clear which part or parts
      of the road ahead supply the visual information needed, or how it is used.
      Current models of the behaviour of real drivers or 'co-driver' simulators vary
      greatly in their implementation of these tasks, but all agree that successful
      steering requires the driver to monitor the angular deviation of the road from
      the vehicle's present heading at some 'preview' distance ahead, typically about 1
      s into the future. Eye movement recordings generally support this view. Here we
      have used a simple road simulator, in which only certain parts of the road are
      displayed, to show that at moderate to high speeds accurate driving requires that
      both a distant and a near region of the road are visible. The former is used to
      estimate road curvature and the latter to provide position-in-lane feedback. At
      lower speeds only the near region is necessary. These results support a two-stage
      model of driver behaviour.

PMID- 7566088
TI  - Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue
      plasminogen activator.
AB  - Neuronal degeneration in the hippocampus, a region of the brain important for
      acquisition of memory in humans, occurs in various pathological conditions,
      including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal
      activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen
      activator (tPA), a serine protease that converts inactive plasminogen to the
      active protease plasmin, is transcriptionally induced. The activity of tPA in
      neural tissue is correlated with neurite outgrowth, regeneration and migration,
      suggesting that it might be involved in neuronal plasticity. Here we show that
      tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to
      induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant
      to neuronal degeneration. These mice are also less susceptible to
      pharmacologically induced seizures than wild-type mice. These findings identify a
      role for tPA in neuronal degeneration and seizure.

PMID- 7566089
TI  - Modulation of GABAA receptors by tyrosine phosphorylation.
AB  - gamma-Aminobutyric acid type-A (GABAA) receptors are the major sites of fast
      synaptic inhibition in the brain. They are presumed to be pentameric
      heteroligomers assembled from four classes of subunits with multiple members:
      alpha (1-6), beta (1-3), gamma (1-3) and delta (1). Here, GABAA receptors
      consisting of alpha 1, beta 1 and gamma 2L subunits, coexpressed in mammalian
      cells with the tyrosine kinase vSRC (the transforming gene product of the Rous
      sarcoma virus), were phosphorylated on tyrosine residues within the gamma 2L and
      beta 1 subunits. Tyrosine phosphorylation enhanced the whole-cell current induced
      by GABA. Site-specific mutagenesis of two tyrosine residues within the predicted
      intracellular domain of the gamma 2L subunit abolished tyrosine phosphorylation
      of this subunit and eliminated receptor modulation. A similar modulation of GABAA
      receptor function was observed in primary neuronal cultures. As GABAA receptors
      are critical in mediating fast synaptic inhibition, such a regulation by tyrosine
      kinases may therefore have profound effects on the control of neuronal
      excitation.

PMID- 7566090
TI  - Induction of apoptosis in mature T cells by tumour necrosis factor.
AB  - T-cell receptor-induced apoptosis regulates immune responses and can result from
      interactions between Fas (Apo1/CD95) and Fas ligand (FasL). Mutations in the
      genes for Fas and FasL cause disorders resembling human autoimmune diseases in
      lpr and gld mice, respectively. However, peripheral T-cell deletion takes place
      in lpr mice, and autoimmune syndromes occur in mouse strains without Fas or FasL
      defects. Here we show that tumour necrosis factor (TNF) can mediate mature T-cell
      receptor-induced apoptosis through the p75 TNF receptor. Blockage of both TNF and
      FasL is required to abrogate T-cell death and TNF mediates the death of most CD8+
      T cells, whereas FasL mediates the death of most CD4+ T cells. Our results
      suggest that autoregulatory apoptosis of the mature T cells can occur by two
      distinct molecular mechanisms.

PMID- 7566091
TI  - Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans
      S182 Alzheimer's disease gene.
AB  - The lin-12 and glp-1 genes of Caenorhabditis elegans are members of the lin
      12/Notch family of receptors for intercellular signals that specify cell fate. By
      screening for suppressors of a lin-12 gain-of-function mutation, we identified a
      new gene, sel-12, which appears to function in receiving cells to facilitate
      signalling mediated by lin-12 and glp-1. The sel-12 gene encodes a protein with
      multiple transmembrane domains, and is similar to S182, which has been implicated
      in early-onset familial Alzheimer's disease. The high degree of sequence
      conservation suggests that the function of the SEL-12 and S182 proteins may also
      be conserved.

PMID- 7566092
TI  - Signalling downstream of activated mammalian Notch.
AB  - Notch belongs to a family of transmembrane proteins that are widely conserved
      from flies to vertebrates and are thought to be involved in cell-fate decisions.
      In Drosophila, the Suppressor of hairless (Su(H)) gene and genes of the Enhancer
      of split (E(Spl)) complex, which encode proteins of the basic helix-loop-helix
      type have been implicated in the Notch signalling pathway. Mammalian homologues
      of E(Spl), such as the mouse Hairy enhancer of split (HES-1), have been isolated.
      Both HES-1 and the intracellular domain of murine Notch (mNotch) are able to
      block MyoD-induced myogenesis. Here we show that activated forms of mNotch
      associate with the human analogue of Su(H), KBF2/RBP-J kappa (refs 8,9) and act
      as transcriptional activators through the KBF2-binding sites of the HES-1
      promoter.

PMID- 7566093
TI  - Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway.
AB  - Insulin-like growth factor (IGF)-II is important for fetal growth and
      development. The human IGF-II gene generates multiple mature transcripts with
      different 5' untranslated regions (5'UTRs) but identical coding regions and
      3'UTRs. We have previously shown that a minor 4.8-kilobase messenger RNA was
      engaged in the synthesis of preproIGF-II, and a major 6.0-kb mRNA was
      untranslated and stored in a 100S ribonucleoprotein particle. Here we demonstrate
      that the 6.0-kb mRNA is selectively mobilized and translated in dispersed
      exponentially growing cells. Translational activation is prevented by rapamycin
      and mimicked by anisomycin, which suggests that translation of the 6.0-kb mRNA is
      regulated by the p70S6k/85S6k kinase signalling pathway. Therefore, the minor 4.8
      kb mRNA generates a constitutive production of prepro-IGF-II, whereas the major
      6.0-kb mRNA provides a post-transcriptionally regulated species.

PMID- 7566094
TI  - Activation of a cell-cycle-regulated histone gene by the oncogenic transcription
      factor IRF-2.
AB  - The human histone H4 gene FO108 is regulated during the cell cycle with a peak in
      transcription during early S phase. The cell-cycle element (CCE) required for H4
      histone activation is a sequence of 11 base pairs that binds a protein factor in
      electrophoretic mobility shift assays that has been designated histone nuclear
      factor M (HiNF-M). Here we report the purification of HiNF-M, and show it to be a
      protein of relative molecular mass (M(r)) 48K that is identical to interferon
      (IFN) regulatory factor 2 (IRF-2), a negative transcriptional regulator of the
      IFN response. Recombinant IRF-2 (as well as the related protein IRF-1 (ref. 5))
      binds the CCE specifically and activates transcription of this H4 histone gene.
      IRF-2 has been shown to have oncogenic potential, and our results demonstrate a
      link between IRF-2 and a gene that is functionally coupled to DNA replication and
      cell-cycle progression at the G1/S phase transition.

PMID- 7566095
TI  - On first looking into the human genome.

PMID- 7566096
TI  - A YAC contig map of the human genome.
AB  - A yeast artificial chromosome library containing 33,000 clones with an average
      insert size of one megabase of human genomic DNA was extensively analysed by
      several different procedures for detecting overlaps and positional information.
      We developed an analysis strategy that resulted, after confirmatory tests, in a
      YAC contig map reliably covering about 75% of the human genome in 225 contigs
      having an average size of about ten megabases.

PMID- 7566097
TI  - A second-generation YAC contig map of human chromosome 3.
AB  - A map of human chromosome 3 which integrates both physical and genetic data has
      been developed from the fusion of two large collections of markers and
      corresponding yeast artificial chromosome (YAC) clones. The map contains 972
      megabase-sized YACs identified with 593 primary markers, of which 162 are highly
      polymorphic sequence-tagged sites (STSs) and form a closely spaced genetic
      linkage map; the remaining markers are hybridization-based. Chromosome 3 is now
      represented by 24 large YAC contigs whose order and orientation is largely known.
      The map generated by fusion of these hybridization- and STS-based datasets covers
      about 80% (over 160 megabases) of the chromosome and will provide the foundation
      necessary for rapid development of a detailed genetic understanding for this
      large autosome.

PMID- 7566098
TI  - Initial assessment of human gene diversity and expression patterns based upon 83
      million nucleotides of cDNA sequence.
AB  - In an effort to identify new genes and analyse their expression patterns, 174,472
      partial complementary DNA sequences (expressed sequence tags (ESTs)), totalling
      more than 52 million nucleotides of human DNA sequence, have been generated from
      300 cDNA libraries constructed from 37 distinct organs and tissues. These ESTs
      have been combined with an additional 118,406 ESTs from the database dbEST, for a
      total of 83 million nucleotides, and treated as a shotgun sequence assembly
      project. The assembly process yielded 29,599 distinct tentative human consensus
      (THC) sequences and 58,384 non-overlapping ESTs. Of these 87,983 distinct
      sequences, 10,214 further characterize previously known genes based on
      statistically significant similarity to sequences in the available databases; the
      remainder identify previously unknown genes. Thirty tissues were sampled by over
      1,000 ESTs each; only eight genes were matched by ESTs from all 30 tissues, and
      227 genes were represented in 20 or more of the tissues sampled with more than
      1,000 ESTs. Approximately 40% of identified human genes appear to be associated
      with basic energy metabolism, cell structure, homeostasis and cell division, 22%
      with RNA and protein synthesis and processing, and 12% with cell signalling and
      communication.

PMID- 7566099
TI  - A second-generation YAC contig map of human chromosome 12.
AB  - Human chromosome 12 constitutes approximately 4.5% of the human genome and has an
      estimated size of 135 million base pairs (Mb). We have started to construct a
      high-resolution physical map of chromosome 12 as overlapping yeast artificial
      chromosomes (YACs), using as a foundation the first-generation physical map of
      this chromosome covers nearly 102 Mb of DNA and includes 426 highly polymorphic,
      monomorphic and gene-based markers. We also mapped 119 of the YACs, most of which
      are part of the physical map, by cytogenetic methods. Thus the map integrates
      genetic, physical and cytogenetic data and provides information about the
      organization of this chromosome and will help in the localization and cloning of
      disease-related genes. The strategy used here to generate the chromosome-12 map
      could be applied for the rapid construction of physical and expression maps for
      other human chromosomes.

PMID- 7566100
TI  - An integrated physical map of human chromosome 16.
AB  - We describe an integrated physical, genetic and cytogenetic map of human
      chromosome 16 comprising both a low-resolution megaYAC map and a high-resolution
      cosmid contig/miniYAC map, which provides nearly complete coverage of the
      euchromatic arms of the chromosome. The physical map is anchored to a high
      resolution cytogenetic breakpoint map and is integrated with genetic and gene
      transcript maps of the chromosome by sequence-tagged sites and clone
      hybridizations.

PMID- 7566101
TI  - A high-density YAC contig map of human chromosome 22.
AB  - We have constructed a high-resolution clone map of human chromosome 22 which
      integrates the available physical and genetic information, establishing a single
      consensus. The map consists of all classes of DNA landmarks ordered on 705 yeast
      artificial chromosomes (YACs) at an average landmark density of more than one per
      70 kilobases. This map represents the practical limits of currently available YAC
      resources and provides the basis for determination of the entire gene content and
      genomic DNA sequence of human chromosome 22.

PMID- 7566102
TI  - Genome diversity alarms.
AB  - The excellent Human Genome Diversity Project needs better planning and a pilot
      project.

PMID- 7566103
TI  - Genetic diversity proposal fails to impress international ethics panel.

PMID- 7566104
TI  - US radiation report prompts bioethics move.

PMID- 7566105
TI  - Court charges open split in Greek earthquake experts.

PMID- 7566106
TI  - Royal Society plans genetics meeting with actuarial profession.

PMID- 7566107
TI  - Medical lobby seeks cuts in US health research agency.

PMID- 7566108
TI  - Visual processing.

PMID- 7566109
TI  - When to help farm animals grow faster.
AB  - The European Commission has broken with precedent by sponsoring an independent
      scientific conference on the role of growth-promoting substances in animal
      husbandry.

PMID- 7566110
TI  - Painful connection for ATP.

PMID- 7566111
TI  - The sound of silence.

PMID- 7566112
TI  - Deja vu all over again.

PMID- 7566113
TI  - Small genomes for better flyers.

PMID- 7566114
TI  - Ligand-independent repression by the thyroid hormone receptor mediated by a
      nuclear receptor co-repressor.
AB  - Thyroid-hormone and retinoic-acid receptors exert their regulatory functions by
      acting as both activators and repressors of gene expression. A nuclear receptor
      co-repressor (N-CoR) of relative molecular mass 270K has been identified which
      mediates ligand-independent inhibition of gene transcription by these receptors,
      suggesting that the molecular mechanisms of repression by thyroid-hormone and
      retinoic-acid receptors are analogous to the co-repressor-dependent
      transcriptional inhibitory mechanisms of yeast and Drosophila.

PMID- 7566115
TI  - Constraints on the origin of the Moon's atmosphere from observations during a
      lunar eclipse.
AB  - The properties of the Moon's rarefied atmosphere, which can be traced through
      observations of sodium and potassium, provide important insights into the
      formation and maintenance of atmospheres on other primitive Solar System bodies.
      The lunar atmosphere is believed to be composed of atoms from the surface rocks
      and soil, which might have been sputtered by micrometeorites, by ions in the
      solar wind, or by photons. It might also form by the evaporation of atoms from
      the hot, illuminated surface. Here we report the detection of sodium emission
      from the Moon's atmosphere during a total lunar eclipse (which occurs when the
      Moon is full). The sodium atmosphere is considerably more extended at full Moon
      than expected--it extends to at least nine lunar radii--and its brightness
      distribution is incompatible with sources involving either solar-wind or
      micrometeorite sputtering. This leaves photon sputtering or thermal desorption as
      the preferred explanations for the lunar atmosphere, and suggests that sunlight
      might also be responsible for the transient atmospheres of other primitive bodies
      (such as Mercury).

PMID- 7566116
TI  - A geochemical model for the formation of hydrothermal carbonates on Mars.
AB  - It is often argued that substantially more carbon dioxide and water were degassed
      from the martian interior than can be found at present in the atmosphere, polar
      caps and regolith. Calculations have shown that atmospheric escape cannot account
      for all of the missing volatiles. Suggestions that carbon dioxide is stored as
      marine or lacustrine deposits, are challenged by Earth-based and spacecraft
      remote-sensing data. Moreover, recent modelling of the martian atmosphere
      suggests that rainfall or open bodies of water are in any case unlikely to have
      persisted for extended periods of time. Hydrothermal carbonates therefore provide
      a possible solution to this dilemma. Using an accessible terrestrial system
      (Iceland) as a guide to the underlying processes, and a host rock composition
      inferred from the least-altered martian meteorite, we present a geochemical model
      for the formation of carbonates in possible martian hydrothermal systems. Our
      results suggest that an extensive reservoir of carbonate minerals--equivalent to
      an atmospheric pressure of carbon dioxide of at least one bar--could have been
      sequestered beneath the surface by widespread hydrothermal activity in the
      martian past.

PMID- 7566117
TI  - Continual change in mate preferences.
AB  - Secondary sexual characters are highly variable both within and between species.
      Closely related species often differ markedly in sexual morphology but hardly at
      all in non-sexual traits. Here we show that Fisher's runaway process of sexual
      selection is intrinsically unstable and naturally leads to continual change in
      sexual traits. Runaway leads to semi-stable exaggeration of female preference for
      a male sexual character, followed by a slow decay of both traits until runaway is
      triggered again in a different direction. The process then repeats itself
      resulting in continual change in male sexual traits through time. Allopatric
      populations are thus expected to diverge without drift or substantial changes in
      selective pressures. If there is significant mutation bias acting on the male
      trait, continual change stops and a stable equilibrium appears. Such an outcome
      is more likely when exaggeration of the male sexual trait signals good genes.

PMID- 7566118
TI  - Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors.
AB  - Dopaminergic neuronal pathways arise from mesencephalic nuclei and project axons
      to the striatum, cortex, limbic system and hypothalamus. Through these pathways
      dopamine affects many physiological functions, such as the control of coordinated
      movement and hormone secretion. Here we have studied the physiological
      involvement of the dopamine D2 receptors in dopaminergic transmission, using
      homologous recombination to generate D2-receptor-deficient mice. Absence of D2
      receptors leads to animals that are akinetic and bradykinetic in behavioural
      tests, and which show significantly reduced spontaneous movements. This phenotype
      presents analogies with symptoms characteristic of Parkinson's disease. Our study
      shows that D2 receptors have a key role in the dopaminergic control of nervous
      function. These mice have therapeutic potential as a model for investigating and
      correcting dysfunctions of the dopaminergic system.

PMID- 7566119
TI  - A P2X purinoceptor expressed by a subset of sensory neurons.
AB  - ATP is known to depolarize sensory neurons, and may play a role in nociceptor
      activation when released from damaged tissue. Here we report the molecular
      cloning and characterization of a new member of the P2X receptor family, P2X3,
      expressed by these cells. The channel transcript was present in a subset of rat
      dorsal-root-ganglion sensory neurons, some of which express nociceptor-associated
      markers; it was absent in other tissues that were tested, including sympathetic,
      enteric and central nervous system neurons. Moreover, when expressed in Xenopus
      oocytes, the channel showed an ATP-dependent cation flux. P2X3 is the only ligand
      gated channel known to be expressed exclusively by a subset of sensory neurons.
      The remarkable selectivity of expression of the channel coupled with its sensory
      neuron-like pharmacology suggests that this channel may transduce ATP-evoked
      nociceptor activation.

PMID- 7566120
TI  - Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated
      currents in sensory neurons.
AB  - Cation-selective P2X receptor channels were first described in sensory neurons
      where they are important for primary afferent neurotransmission and nociception.
      Here we report the cloning of a complementary DNA (P2X3) from rat dorsal root
      ganglia that had properties dissimilar to those of sensory neurons. We also found
      RNA for (P2X1)(ref. 7), (P2X2)(ref. 8) and P2X4 (ref. 9) in sensory neurons;
      channels expressed from individual cDNAs did not reproduce those of sensory
      ganglia. Coexpression of P2X3 with P2X2, but not other combinations, yielded ATP
      activated currents that closely resembled those in sensory neurons. These
      properties could not be accounted for by addition of the two sets of channels,
      indicating that a new channel had formed by subunit heteropolymerization.
      Although in some tissues responses to ATP can be accounted for by homomeric
      channels, our results indicate that ATP-gated channels of sensory neurons may
      form by a specific heteropolymerization of P2X receptor subunits.

PMID- 7566121
TI  - Streptococcus pneumoniae anchor to activated human cells by the receptor for
      platelet-activating factor.
AB  - The Gram-positive bacterium Streptococcus pneumoniae is a major cause of
      pneumonia, sepsis and meningitis. Although the invasive disease is severe, some
      40% of individuals harbour the pneumococcus in the nasopharynx asymptomatically.
      Here we investigate the molecular elements of the encounter between host and
      pathogen that distinguish these different outcomes. We show that inflammatory
      activation of human cells shifts the targeting of the pneumococcus to a new
      receptor, that for the G-protein-coupled platelet-activating factor (PAF). Only
      virulent pneumococci engage the PAF receptor. Attachment of the bacterial
      phosphorylcholine to the PAF receptor enhanced adherence, which was coupled to
      invasion of endothelial, epithelial and PAF-receptor-transfected cells. This
      progression could be arrested in vitro and in vivo by PAF-receptor-specific
      antagonists, suggesting a possible approach to therapy.

PMID- 7566122
TI  - Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis
      oocytes.
AB  - In Xenopus oocytes, as well as other cells, inositol-1,4,5-trisphosphate
      (Ins(1,4,5)P3)-induced Ca2+ release is an excitable process that generates
      propagating Ca2+ waves that annihilate upon collision. The fundamental property
      responsible for excitability appears to be the Ca2+ dependency of the
      Ins(1,4,5)P3 receptor. Here we report that Ins(1,4,5)P3-induced Ca2+ wave
      activity is strengthened by oxidizable substrates that energize mitochondria,
      increasing Ca2+ wave amplitude, velocity and interwave period. The effects of
      pyruvate/malate are blocked by ruthenium red at the Ca2+ uniporter, by rotenone
      at complex I, and by antimycin A at complex III, and are subsequently rescued at
      complex IV by ascorbate tetramethylphenylenediamine (TMPD). Our data reveal that
      potential-driven mitochondrial Ca2+ uptake is a major factor in the regulation of
      Ins(1,4,5)P3-induced Ca2+ release and clearly demonstrate a physiological role of
      mitochondria in intracellular Ca2+ signalling.

PMID- 7566123
TI  - Control of p70 s6 kinase by kinase activity of FRAP in vivo.
AB  - When complexed with the intracellular protein FKBP12, rapamycin is a potent
      immunosuppressant and an inhibitor of a mitogen-stimulated signalling pathway
      that leads to activation of p70 S6 kinase (p70S6k) and cyclin-dependent kinases
      (CDKs). A recently cloned FKBP12-rapamycin-associated protein (FRAP/RAFT) is the
      likely mediator of these effects. Using FRAP variants that do not bind FKBP12
      rapamycin, we demonstrate here that FRAP is a rapamycin-sensitive regulator of
      p70S6k in vivo and that the kinase activity of FRAP is required for this
      regulation. In addition, we show that FRAP autophosphorylates in vitro.
      Consistent with an essential role for FRAP kinase activity in vivo,
      autophosphorylation of FRAP is inhibited by FKBP12-rapamycin. Deletion studies
      indicate that the kinase activity of FRAP alone is not sufficient for control of
      p70S6k and that an amino-terminal domain in FRAP is also required.

PMID- 7566124
TI  - Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme
      B.
AB  - Cytotoxic T lymphocyte (CTL)-mediated cytotoxicity represents the body's major
      defence against virus-infected and tumorigenic cells, and contributes to
      transplant rejection and autoimmune disease. During killing, CTL granules are
      exocytosed, releasing their contents into the intercellular space between the
      target cell and the effector. Perforin facilitates the entry of cytotoxic cell
      serine proteases, the granzymes, into the target cell, where they induce
      apoptotic death by an unknown pathway. Granzyme B is essential for the induction
      of DNA fragmentation and apoptosis in target cells, yet its substrate is unknown.
      Identification of the intracellular substrate for granzyme B is therefore the key
      to understanding the mechanism of CTL-mediated killing. Here we show that
      granzyme B cleaves and activates CPP32, the precursor of the protease responsible
      for cleavage of poly(ADP-ribose) polymerase.

PMID- 7566125
TI  - Highly processive microtubule-stimulated ATP hydrolysis by dimeric kinesin head
      domains.
AB  - Studies of immobilized kinesin have shown that a single dimeric molecule can
      maintain contact with and drive sliding of a microtubule. In solution, however,
      native kinesin binds microtubules too weakly and hydrolyses ATP too slowly to
      produce the high sliding velocities seen in motility assay. This apparent
      inhibition in solution appears to be caused by the binding of kinesin's tail
      domains to its motor (head) domains in a folded conformation. DKH392, a construct
      containing two heads but no tails, has been shown to display both tight binding
      to microtubules and high ATPase rates. Furthermore, it retains one molecule of
      ADP per dimer when bound to microtubules, which could facilitate a 'hand-over
      hand' mechanism for processive motion. Here we show that DKH392 hydrolyses more
      than 100 ATP molecules per diffusional encounter with a microtubule, even in the
      high-salt conditions encountered physiologically. This provides direct evidence
      that kinesin's activity is highly processive, with the motor remaining attached
      to a microtubule through many cycles of ATP hydrolysis.

PMID- 7566126
TI  - Polarity-specific activities of retinoic acid receptors determined by a co
      repressor.
AB  - Retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) activate or
      repress transcription by binding as heterodimers to DNA-response elements that
      generally consist of two direct repeat half-sites of consensus sequence AGGTCA.
      On response elements consisting of direct repeats spaced by five base pairs (DR +
      5 elements), RAR/RXR heterodimers activate transcription in response to RAR
      specific ligands, such as all-trans-retinoic acid (RA). In contrast, on elements
      consisting of direct repeats spaced by one base pair (DR + 1 elements), RAR/RXR
      heterodimers exhibit little or no response to activating ligands and repress RXR
      dependent transcription. Here we show that ligand-dependent transactivation by
      RAR on DR + 5 elements requires the dissociation of a new nuclear receptor co
      repressor, N-CoR, and recruitment of the putative co-activators p140 and p160.
      Surprisingly, on DR + 1 elements, N-CoR remains associated with RAR/RXR
      heterodimers even in the presence of RAR ligands, resulting in constitutive
      repression. These observations indicate that DNA-response elements can
      allosterically regulate RAR-co-repressor interactions to determine positive or
      negative regulation of gene expression.

PMID- 7566128
TI  - Nobel committee rewards pioneers of development studies in fruitflies.

PMID- 7566127
TI  - A transcriptional co-repressor that interacts with nuclear hormone receptors.
AB  - Transcriptional silencing mediated by nuclear receptors is important in
      development, differentiation and oncogenesis. The mechanism underlying this
      effect is unknown but is one key to understanding the molecular basis of hormone
      action. Here we identify a receptor-interacting factor, SMRT, as a silencing
      mediator (co-repressor) for retinoid and thyroid-hormone receptors. SMRT is a
      previously undiscovered protein whose association with receptors both in solution
      and bound to DNA-response elements is destabilized by ligand. The interaction
      with mutant receptors correlates with their transcriptional silencing activities.
      In vivo, SMRT functions as a potent co-repressor, and a GAL4 DNA-binding domain
      fusion of SMRT behaves as a frank repressor of a GAL4-dependent reporter.
      Together, our results identify a new class of cofactors which may be important
      mediators of hormone action.

PMID- 7566129
TI  - Britain must tackle 'genetic illiteracy' among new doctors.

PMID- 7566130
TI  - HIV compensation package under offer.

PMID- 7566131
TI  - Medical bodies secure 'safe' data network.

PMID- 7566132
TI  - Austrian universities come under scrutiny...

PMID- 7566133
TI  - US radiation report fails to satisfy critics.

PMID- 7566134
TI  - Hidden meaning.

PMID- 7566135
TI  - Cost of psychiatric care.

PMID- 7566136
TI  - Salk and science.

PMID- 7566137
TI  - Fraud and hoaxes in science.
AB  - The recent spate of moral condemnation of fraud in science reflects the
      conservative nature of scientists; fraud, like error, is a normal part of science
      and cannot be legislated away.

PMID- 7566138
TI  - Nature on the Internet (at last)!

PMID- 7566139
TI  - Pharmacology. Home for an orphan endorphin.

PMID- 7566140
TI  - Evolutionary biology. A twofold tragedy unfolds.

PMID- 7566141
TI  - Transcription. Clamping the TBP stirrup.

PMID- 7566142
TI  - Flower development. LEAFY blooms in aspen.

PMID- 7566143
TI  - Developmental biology. New role for tropomyosin.

PMID- 7566144
TI  - Touching the phantom limb.

PMID- 7566145
TI  - tRNA editing in metazoans.

PMID- 7566146
TI  - A developmental switch sufficient for flower initiation in diverse plants.
AB  - We have generated transgenic plants in which the flower-meristem-identity gene
      LEAFY of Arabidopsis is constitutively expressed. LEAFY is sufficient to
      determine floral fate in lateral shoot meristems of both Arabidopsis and the
      heterologous species aspen, with the consequence that flower development is
      induced precociously. Our results also suggest a new level of regulation during
      flower development, as indicated by the competence of the main shoot to respond
      to LEAFY activity.

PMID- 7566147
TI  - Mutual policing and repression of competition in the evolution of cooperative
      groups.
AB  - Evolutionary theory has not explained how competition among lower level units is
      suppressed in the formation of higher-level evolutionary units. For example, the
      key problem of early evolution is small, individual replicators formed
      cooperative groups of sufficient complexity to allow accurate copying of the
      genetic material. The puzzle is why parasites did not subvert the formation of
      cells by obtaining benefits from the group without contributing to shared traits
      that enhance reproduction. These parasites would outcompete other replicators
      within the cell, disrupting reproductive fairness among subunits and destroying
      the functional coherence of the group. A similar problem arose at a later
      evolutionary stage with the orderly mendelian segregation of subunits
      (chromosomes) within cells, and reproductive fairness continued to be a problem
      in the evolution of insect and human societies. Here I present a simple model to
      show how reproductive fairness evolves among subunits to create functional
      coherence and higher-level units. Self-restraint, which evolves according to the
      kin-selection coefficient of relatedness, is not sufficient: mutual policing and
      enforcement of reproductive fairness are also required for the evolution of
      increasing social complexity.

PMID- 7566148
TI  - A gene triggering flower formation in Arabidopsis.
AB  - In Arabidopsis, the apical shoot meristem produces lateral meristems that develop
      into either shoots or flowers. The decision to form flowers instead of shoots is
      mediated by the action of floral-meristem-identity genes, such as APETALA1 (AP1)
      and LEAFY (LFY), which specify meristem fate. Here we show that transgenic plants
      which constitutively express the AP1 gene show transformations of apical and
      lateral shoots into flowers, and that these plants flower much earlier than wild
      type plants. These results indicate that AP1 alone can convert infloresence shoot
      meristems into floral meristems, and that ectopic AP1 expression can dramatically
      reduce the time to flowering.

PMID- 7566149
TI  - Requirement for Drosophila cytoplasmic tropomyosin in oskar mRNA localization.
AB  - The localization of oskar (osk) RNA to the posterior pole of the developing fruit
      fly (Drosophila) oocyte induces the assembly of pole plasm, causing development
      of the abdomen and germ line. Failure to localize oskar RNA results in embryos
      that lack abdomen and germ cells. Conversely, mis-targeting of oskar RNA to the
      anterior of the oocyte causes formation of ectopic abdomen and germ cells at the
      anterior pole. Maternal mutants that have reduced pole plasm activity produce
      sterile adults with normal abdominal development, suggesting that germ cells are
      more sensitive than abdomen to defects in pole plasm assembly. Thus mutations in
      genes that reduce oskar RNA localization or activity can be recovered as viable
      sterile adults. In a screen for mutants defective in germ cell formation, we
      isolated nine alleles of the tropomyosin II gene. Here we show that mutations in
      tropomyosin II (TmII) virtually abolish oskar RNA localization to the posterior
      pole, suggesting an involvement of the actin network in oskar RNA localization.

PMID- 7566150
TI  - Transient increase in obese gene expression after food intake or insulin
      administration.
AB  - Obesity is a disorder of energy balance, indicating a chronic disequilibrium
      between energy intake and expenditure. Recently, the mouse ob gene, and
      subsequently its human and rat homologues, have been cloned. The ob gene product,
      leptin, is expressed exclusively in adipose tissue, and appears to be a
      signalling factor regulating body-weight homeostasis and energy balance. Because
      the level of ob gene expression might indicate the size of the adipose depot, we
      suggest that it is regulated by factors modulating adipose tissue size. Here we
      show that ob gene exhibits diurnal variation, increasing during the night, after
      rats start eating. This variation was linked to changes in food intake, as
      fasting prevented the cyclic variation and decreased ob messenger RNA.
      Furthermore, refeeding fasted rats restored ob mRNA within 4 hours to levels of
      fed animals. A single insulin injection in fasted animals increased ob mRNA to
      levels of fed controls. Experiments to control glucose and insulin independently
      in animals, and studies in primary adipocytes, showed that insulin regulates ob
      gene expression directly in rats, regardless of its glucose-lowering effects.
      Whereas the ob gene product, leptin, has been shown to reduce food intake and
      increase energy expenditure, our data demonstrate that ob gene expression is
      increased after food ingestion in rats, perhaps through a direct action of
      insulin on the adipocyte.

PMID- 7566151
TI  - The role of neuropeptide Y in the antiobesity action of the obese gene product.
AB  - Recently Zhang et al. cloned a gene that is expressed only in adipose tissue of
      the mouse. The obese phenotype of the ob/ob mouse is linked to a mutation in the
      obese gene that results in expression of a truncated inactive protein. Human and
      rat homologues for this gene are known. Previous experiments predict such a
      hormone to have a hypothalamic target. Hypothalamic neuropeptide Y stimulates
      food intake, decreases thermogenesis, and increases plasma insulin and
      corticosterone levels making it a potential target. Here we express the obese
      protein in Escherichia coli and find that it suppresses food intake and decreases
      body weight dramatically when administered to normal and ob/ob mice but not db/db
      (diabetic) mice, which are thought to lack the appropriate receptor. High
      affinity binding was detected in the rat hypothalamus. One mechanism by which
      this protein regulated food intake and metabolism was inhibition of neuropeptide
      Y synthesis and release.

PMID- 7566152
TI  - Isolation and structure of the endogenous agonist of opioid receptor-like ORL1
      receptor.
AB  - The ORL1 receptor, an orphan receptor whose human and murine complementary DNAs
      have recently been characterized, structurally resembles opioid receptors and is
      negatively coupled with adenylate cyclase. ORL1 transcripts are particularly
      abundant in the central nervous system. Here we report the isolation, on the
      basis of its ability to inhibit the cyclase in a stable recombinant CHO(ORL1+)
      cell line, of a neuropeptide that resembles dynorphin A9 and whose amino acid
      sequence is Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln.
      The rat-brain cDNA encodes the peptide flanked by Lys-Arg proteolytic cleavage
      motifs. The synthetic heptadecapeptide potently inhibits adenylate cyclase in
      CHO(ORL1+) cells in culture and induces hyperalgesia when administered
      intracerebroventricularly to mice. Taken together, these data indicate that the
      newly discovered heptadecapeptide is an endogenous agonist of the ORL1 receptor
      and that it may be endowed with pro-nociceptive properties.

PMID- 7566153
TI  - Negative regulation of T-cell adhesion and activation by CD43.
AB  - CD43 is a cell-surface sialoglycoprotein expressed by a variety of
      haematopoietically derived cells, including T lymphocytes. Earlier observations
      of defective CD43 expression by T lymphocytes from boys with the X-chromosome
      linked Wiskott-Aldrich syndrome suggested the importance of CD43 in lymphocyte
      function. Subsequent studies have suggested that CD43 facilitates leukocyte
      adhesion and has a co-stimulatory role during T-cell activation. To define the
      physiologically relevant function(s) of CD43, we have generated CD43-knockout
      mice. We report here that CD43-deficient T cells from such mice show a marked
      increase in their in vitro proliferative response to concanavalin A, anti-CD3,
      the superantigen SEB and allostimulation. Additionally, CD43-deficient T cells
      show a substantial enhancement in homotypic adhesion and in their ability to bind
      different ligands, including fibronectin and the intercellular adhesion molecule
      ICAM-1. Vaccinia-virus-infected CD43-knockout mice mounted an augmented anti
      vaccinia cytotoxic T-cell response compared with their wild-type littermates, yet
      developed an increased virus load. We conclude that CD43 negatively regulates T
      cell activation and adhesion and is important for viral clearance.

PMID- 7566154
TI  - Reduced cell motility and enhanced focal adhesion contact formation in cells from
      FAK-deficient mice.
AB  - The intracellular protein tyrosine kinase FAK (focal adhesion kinase) was
      originally identified gy its high level of tyrosine phosphorylation in v-src
      transformed cells. FAK is also highly phosphorylated during early development. In
      cultured cells it is localized to focal adhesion contacts and becomes
      phosphorylated and activated in response to integrin-mediated binding of cells to
      the extracellular matrix, suggesting an important role in cell adhesion and/or
      migration. We have generated FAK-deficient mice by gene targeting to examine the
      role of FAK during development. Mutant embryos displayed a general defect of
      mesoderm development, and cells from these embryos had reduced mobility in vitro.
      Surprisingly, the number of focal adhesions was increased in FAK-deficient cells,
      suggesting that FAK may be involved in the turnover of focal adhesion contacts
      during cell migration.

PMID- 7566155
TI  - A role for phosphatidylinositol transfer protein in secretory vesicle formation.
AB  - Vesicular traffic in eukaryotic cells is characterized by two steps of membrane
      rearrangement: the formation of vesicles from donor membranes and their fusion
      with acceptor membranes. With respect to vesicle formation, several of the
      cytosolic proteins implicated in budding and fission have been identified. A
      feature common to all these proteins is that their targets, when known, are other
      proteins rather than lipids. Here we report, using a previously established cell
      free system derived from a neuroendocrine cell line, the purification of
      cytosolic factors that stimulate the formation of constitutive secretory vesicles
      and immature secretory granules from the trans-Golgi network. One such factor,
      referred to as CAST1, was identified as the alpha and beta isoforms of the
      mammalian phosphatidylinositol transfer protein (PtdIns-TP) (refs 3-5). The yeast
      PtdIns-TP, SEC14p (ref. 6), which has no sequence homology to mammalian PtdIns-TP
      (refs 7,8), was able to substitute for the mammalian PtdIns-TP in secretory
      vesicle formation. Our results suggest a highly conserved role for
      phosphoinositides in vesicle formation.

PMID- 7566156
TI  - A WD-domain protein that is associated with and phosphorylated by the type II TGF
      beta receptor.
AB  - Transforming growth factor-beta (TGF-beta) is the prototype for a family of
      extracellular polypeptides that affect cell proliferation and differentiation,
      and tissue morphogenesis. TGF-beta signalling is mediated by two types of
      serine/threonine kinase receptors, the type I and II receptors, which are able to
      form a heteromeric complex. No cytoplasmic proteins that associate with these
      receptors in vivo, or are their kinase targets, have yet been described. We have
      now identified a WD-domain-containing protein, TRIP-1, which specifically
      associates with the type II TGF-beta receptor in a kinase-dependent way. TRIP-1
      does not interact with the type II activin or type I receptors, but associates
      with the heteromeric TGF-beta receptor complex. TRIP-1 is phosphorylated on
      serine and threonine by the receptor kinase, strongly suggesting that it has a
      role in TGF-beta signalling. This is supported by coexpression of TRIP-1 and type
      II receptor during development. The existence of TRIP-1 homologues in plant and
      yeast suggests a conserved function in all eukaryotes.

PMID- 7566157
TI  - Radiation-induced cell cycle arrest compromised by p21 deficiency.
AB  - The protein p21 is a dual inhibitor of cyclin-dependent kinases and proliferating
      cell nuclear antigen (PCNA), both of which are required for passage through the
      cell cycle. The p21 gene is under the transcriptional control of p53 (ref. 5),
      suggesting that p21 might promote p53-dependent cell cycle arrest or apoptosis.
      p21 has also been implicated in cell senescence and in cell-cycle withdrawal upon
      terminal differentiation. Here we investigate the role of p21 in these processes
      using chimaeric mice composed partly of p21-/- and partly of p21+/+ cells.
      Immunohistochemical studies of the p21+/+ and p21-/- components of adult small
      intestine indicated that deletion of p21 has no detectable effect on the
      migration-associated differentiation of the four principal intestinal epithelial
      cell lineages or on p53-dependent apoptosis following irradiation. However, p21-/
      mouse embryo fibroblasts are impaired in their ability to undergo G1 arrest
      following DNA damage.

PMID- 7566158
TI  - Requirement for TFIIH kinase activity in transcription by RNA polymerase II.
AB  - An array of tandem heptapeptide repeats at the carboxy-terminal domain (CTD) of
      the largest subunit of RNA polymerase II constitute a highly conserved structure
      essential for viability. Studies have established that the CTD is phosphorylated
      at different stages of the transcription cycle, and that it may be involved in
      transcriptional regulation. The exact role of the CTD remains elusive, as in
      vitro reconstituted transcription using the adenovirus major late promoter does
      not require the CTD. Previous studies showed that transcription from the murine
      dihydrofolate reductase (DHFR) promoter can be only accomplished by the form of
      RNA polymerase II that contains the hypophosphorylated CTD (RNAPIIA), but not by
      the form that lacks it (RNAPIIB). Here we show that the CTD, but not its
      phosphorylation, is required for initiation of transcription. We also show that
      transcription requires CTD kinase activity provided by the CDK subunit of TFIIH.

PMID- 7566159
TI  - Time to ban British boxing.
AB  - Cockfighting and bear-baiting have been banned for several decades in most grown
      up countries, but fist-fights between people are tragically still allowed.

PMID- 7566160
TI  - Nuclear regulators to investigate 'contamination' incident at MIT.

PMID- 7566161
TI  - FBI investigates radiation exposure claims.

PMID- 7566162
TI  - Inquiry at Harvard prompts research paper corrections.

PMID- 7566163
TI  - Anthropology and race.

PMID- 7566164
TI  - Developmental biology. Making one cell from two.

PMID- 7566165
TI  - Immunology. Ways around rejection.

PMID- 7566166
TI  - Cancer chemotherapy. Heavy metal revival.

PMID- 7566167
TI  - Psychology. Insight into intelligence.

PMID- 7566168
TI  - Baseball teams beaten by jet lag.

PMID- 7566169
TI  - Masculinization costs in hyaenas.

PMID- 7566170
TI  - Neanderthal infant burial.

PMID- 7566171
TI  - Cytokine receptor signalling.
AB  - Many cell functions are regulated by members of the cytokine receptor
      superfamily. Signalling by these receptors depends upon their association with
      Janus kinases (JAKs), which couple ligand binding to tyrosine phosphorylation of
      signalling proteins recruited to the receptor complex. Among these are the signal
      transducers and activators of transcription (STATs), a family of transcription
      factors that contribute to the diversity of cytokine responses.

PMID- 7566172
TI  - Asymmetric segregation of Numb and Prospero during cell division.
AB  - A cell can divide asymmetrically by specifically segregating a determinant into
      one of its daughter cells. The Numb protein is a candidate for such a determinant
      in the asymmetric cell divisions of the developing Drosophila nervous system.
      Numb is a membrane-associated protein that localizes asymmetrically during cell
      division and segregates into one daughter cell, where it is required for the
      specification of the correct cell fate. Here we show that a nuclear protein,
      Prospero, translocates to the membrane at the beginning of cell division and
      colocalizes with Numb throughout mitosis, suggesting a common mechanism for
      asymmetric segregation. Numb and Prospero localization is coupled to mitosis and
      tightly correlated with the position of one of the two centrosomes. In contrast
      to centrosome positioning, however, Numb and Prospero localization is independent
      of microtubules. Cytochalasin D treatment suggests that the process is also
      independent of actin. We propose that there is an organizer of asymmetric cell
      division which provides positional information for both the orientation of the
      mitotic spindle and asymmetric localization of Numb and Prospero.

PMID- 7566173
TI  - Asymmetric segregation of the homeodomain protein Prospero during Drosophila
      development.
AB  - Asymmetric divisions that produce two distinct cells play fundamental roles in
      generating different cell types during development. In the Drosophila central
      nervous system, neural stem cells called neuroblasts divide unequally into
      another neuroblast and a ganglion mother cell which is subsequently cleaved into
      neurons. Correct gene expression of ganglion mother cells requires the
      transcription factor Prospero. Here we demonstrate the asymmetric segregation of
      Prospero on neuroblast division. Prospero synthesized in neuroblasts is retained
      in the cytoplasm and at mitosis is exclusively partitioned to ganglion mother
      cells, in which it is translocated to the nucleus. Differential segregation of
      Prospero was also found in the endoderm. We have identified a region in Prospero
      that is responsible for this event. The region shares a common motif with Numb,
      which also shows unequal segregation. We propose that asymmetric segregation of
      transcription factors is an intrinsic mechanism for establishing asymmetry in
      gene expression between sibling cells.

PMID- 7566174
TI  - A role for CD95 ligand in preventing graft rejection.
AB  - Testis is a remarkable immune-privileged site, long known for its ability to
      support allogeneic and xenogeneic tissue transplants. Here we have investigated
      the molecular basis for testis immune privilege. Testis grafts derived from mice
      that can express functional CD95 (Fas or Apo-1) ligand survived indefinitely when
      transplanted under the kidney capsule of allogeneic animals, whereas testis
      grafts derived from mutant gld mice, which express non-functional ligand, were
      rejected. Further analysis of testis showed that CD95 ligand messenger RNA is
      constitutively expressed by testicular Sertoli cells, and that Sertoli cells from
      normal mice, but not gld mice, were accepted when transplanted into allogeneic
      recipients. CD95 ligand expression in the testis probably acts by inducing
      apoptotic cell death of CD95-expressing, recipient T cells activated in response
      to graft antigens. These findings indicate that CD95 ligand could be used to
      create immune-privileged tissue for a variety of transplant uses.

PMID- 7566175
TI  - Protection against mycoplasma infection using expression-library immunization.
AB  - As is evident from the human immunodeficiency virus epidemic, there is no
      systematic method for producing a vaccine. Genetic immunization is a new approach
      to vaccine production that has many of the advantages of live/attenuated
      pathogens but no risk of infection. It involves introducing DNA encoding a
      pathogen protein into host cells and has shown promise in several disease models.
      Here we describe a new method for vaccine development, expression-library
      immunization, which makes use of the technique of genetic immunization and the
      fact that all the antigens of a pathogen are encoded in its DNA. An expression
      library of pathogen DNA is used to immunize a host thereby producing the effects
      of antigen presentation of a live vaccine without the risk. We show that even
      partial expression libraries made from the DNA of Mycoplasma pulmonis, a natural
      pathogen in rodents, provide protection against challenge from the pathogen.
      Expression library immunization may prove to be a general method for vaccination
      against any pathogen.

PMID- 7566176
TI  - Increased T-cell apoptosis and terminal B-cell differentiation induced by
      inactivation of the Ets-1 proto-oncogene.
AB  - The Ets-1 proto-oncogene is a member of a transcription factor family
      characterized by homology to the v-ets oncogene. In adult mice, Ets-1 is
      expressed predominantly in lymphoid cells where it has been implicated in
      regulating transcription of lymphocyte-specific genes. Following T-cell
      activation, the specific DNA binding activity of Ets-1 is inactivated by
      transient phosphorylation, suggesting a function in the transition from the
      resting to activated state. Ets-1 has also been suggested to cooperate with the
      AP-1 transcription factor complex to mediate cellular growth factor responses.
      Here we show, by using RAG-2-deficient blastocyst complementation, that Ets-1
      deficiency has dramatic, but different, effects on development and function of T-
      and B-lineage cells. Ets-1-deficient T cells were present in reduced numbers and
      were highly susceptible to cell death in vitro. In contrast, Ets-1-deficient B
      cells were present in normal numbers but a large proportion were IgM plasma
      cells. Our data demonstrate that Ets-1 is essential for maintenance of the normal
      pool of resting T- and B-lineage cells.

PMID- 7566177
TI  - Defective activation and survival of T cells lacking the Ets-1 transcription
      factor.
AB  - The Ets-1 proto-oncogene is a member of the Ets family of eukaryotic
      transcription factors. Members of this family play important roles in regulating
      gene expression in response to multiple developmental and mitogenic signals. Ets
      1 is preferentially expressed at high levels in B and T cells of adult mice and
      is regulated during both thymocyte development and T-cell activation. To study
      the role of Ets-1 in T-cell development and function we have used the RAG-2-/-
      complementation system and murine embryonic stem (ES) cells containing homozygous
      deletions in the Ets-1 gene (Ets-1-/-). Ets-1-/(-)-RAG-2-/- chimaeric mice
      displayed markedly decreased numbers of mature thymocytes and peripheral T cells.
      Ets-1-/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)
      alpha/beta. However, they displayed a severe proliferative defect in response to
      multiple activational signals and demonstrated increased rates of spontaneous
      apoptosis in vitro. These findings demonstrate that Ets-1 is required for the
      normal survival and activation of murine T cells.

PMID- 7566178
TI  - Membrane-restricted regulation of Ca2+ release and influx in polarized epithelia.
AB  - Epithelial cells exist in a complex setting in which responses to mucosal or
      serosal environments are mediated by receptors expressed on specialized cellular
      domains, such as apical versus basolateral cell membranes. We investigated
      whether airway epithelia can react selectively through G-protein-coupled
      receptors to stimuli in the mucosal or serosal environments by measuring inositol
      phosphate and intracellular Ca2+ responses in polarized human nasal epithelial
      monolayers. We report here that unilateral ATP (10(-4) M) administration
      stimulated P2 purinoceptors and tapped pools of intracellular Ca2+ associated
      with the plasma membrane ipsilateral but not contralateral to stimulated
      receptors. Similarly, activation of plasma membrane Ca2+ influx by ATP was
      confined to the membrane ipsilateral to receptor stimulation. These findings
      demonstrate that polarized epithelia restrict P2 receptor-mediated responses to a
      single domain of the cell, reflecting membrane-specific generation and catabolism
      of inositol phosphates and confinement of calcium influx regulation to the
      membrane ipsilateral to the stimulated receptors.

PMID- 7566179
TI  - Induction of the growth inhibitor IGF-binding protein 3 by p53.
AB  - Transcriptional activation of target genes represents an important component of
      the tumour-suppressor function of p53 and provides a functional link between p53
      and various growth-regulatory processes, including cell cycle progression
      (p21/WAF1), DNA repair (GADD45) and apoptosis (bax). Here we use a differential
      cloning approach to identify the gene encoding insulin-like growth factor binding
      protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3
      gene expression by wild-type but not mutant p53 is associated with enhanced
      secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling
      by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may
      link p53 to potential novel autocrine/paracrine signalling pathways and to
      processes regulated by or dependent on IGF(s), such as cellular growth,
      transformation and survival.

PMID- 7566180
TI  - Crystal structure of double-stranded DNA containing the major adduct of the
      anticancer drug cisplatin.
AB  - The success of cisplatin in cancer chemotherapy derives from its ability to
      crosslink DNA and alter the structure. Most cisplatin-DNA adducts are intrastrand
      d(GpG) and d(ApG) crosslinks, which unwind and bend the duplex to facilitate the
      binding of proteins that contain one or more high-mobility group (HMG) domains.
      When HMG-domain proteins such as HMG1, IXR (intrastrand-crosslink recognition)
      protein from yeast, or human upstream-binding factor (hUBF) bind cisplatin
      intrastrand crosslinks, they can be diverted from their natural binding sites on
      the genome and shield the adducts from excision repair. These activities
      sensitize cells to cisplatin and contribute to its cytotoxic properties.
      Crystallographic information about the structure of cisplatin-DNA adducts has
      been limited to short single-stranded deoxyoligonucleotides such as cis
      [Pt(NH3)2(d(pGpG))]. Here we describe the X-ray structure at 2.6 A resolution of
      a double-stranded DNA dodecamer containing this adduct. Our information provides,
      to our knowledge, the first crystallographic look at a platinated DNA duplex and
      should help the design of new platinum and other metal crosslinking antitumour
      drug candidates. Moreover, the structure reveals a unique fusion of A- and B-type
      DNA segments that could be of more general importance.

PMID- 7566182
TI  - Plasmid-based transgenic mouse model for studying in vivo mutations.
AB  - A new transgenic mouse model for studying in vivo somatic mutations is based on
      the efficient recovery of chromosomally integrated lacZ-containing plasmids,
      using magnetic beads.

PMID- 7566181
TI  - A metalloprotease-disintegrin participating in myoblast fusion.
AB  - Skeletal muscle development involves the formation of multi-nucleated myotubes.
      This is thought to proceed by the induction of differentiation (acquisition of
      fusion competence) of myoblast cells, their aggregation, and union of their
      plasma membranes. Various membrane proteins including N- and M-cadherins, N- and
      V-CAMs and integrins participate in myotube formation, but the molecular
      mechanisms of muscle cell fusion are poorly understood. Here we report the
      identification of three new, myoblast-expressed gene products, meltrin-alpha,
      beta and gamma, with homology to both viper haemorrhagic factors and fertilin (PH
      30), a membrane protein involved in egg-sperm fusion. Meltrin-alpha, a member of
      the metalloproteinase/disintegrin protein family, appears to be required for
      myotube formation. Involvement of a fertilin-related protein in myogenesis
      suggests that there are common mechanisms in gamete and myoblast fusion.

PMID- 7566184
TI  - The dangers of being a doctor.

PMID- 7566183
TI  - Auditory sensitization during the perception of acoustical negative afterimages:
      analogies to visual processing?

PMID- 7566185
TI  - To pee or not to pee.

PMID- 7566186
TI  - To pee or not to pee.

PMID- 7566187
TI  - Primary care physicians for North Carolina. How many are needed? Where will they
      come from? Can the need be met?

PMID- 7566188
TI  - A graduate survey of the relevance of a family practice residency curriculum.

PMID- 7566189
TI  - Could changes in the health care system force North Carolina to establish a
      health services commission?

PMID- 7566190
TI  - Staying dry during the night.

PMID- 7566191
TI  - Immune-based therapy of multiple sclerosis.

PMID- 7566192
TI  - Postpartum psychiatric disorders. A guide for the practicing physician.

PMID- 7566193
TI  - Acute myocardial infarction. A guide for North Carolina doctors.

PMID- 7566194
TI  - The clinical significance of spontaneous pneumobilia.

PMID- 7566195
TI  - Three rear ends on the beach. Debating the ethics of medical advertising.

PMID- 7566196
TI  - Reimbursement and ESRD. The future of managed care and the ESRD program.

PMID- 7566197
TI  - The changing face of renal care providers: who will dominate the market?

PMID- 7566198
TI  - Physician ownership revisited. Alliances, joint ventures, and easing regulations
      help to revive interest for independent facilities.

PMID- 7566199
TI  - Highway to computerization can be bumpy, but worth the trip for the renal team.

PMID- 7566200
TI  - Strengthening managed care negotiations with targeted data analyses.

PMID- 7566201
TI  - Computerizing billing and patient management data in a dialysis unit.

PMID- 7566202
TI  - Core indicator study: evaluating the results.

PMID- 7566203
TI  - If I had been in charge of the guest list...

PMID- 7566205
TI  - Quality oversight: how much is too much?
AB  - Concern for quality, which has created $1 billion/year quality oversight
      businesses, has affected health care organizations financially in different
      degrees. The most costly is the JCAHO accreditation process. Health care
      organizations have the power to control these businesses and expenditures.

PMID- 7566204
TI  - An interview with Ann Marie Brooks. Interview by Neale Miller.
AB  - Ann Marie Brooks, DNSc, MBA, RN, FAAN, projects an enviable kind of strength
      coupled with a refreshingly egalitarian style. While her ten-page resume conveys
      something of her professional power and personal influence, her effectiveness,
      along with her customary modesty, has made her a viable role model for those who
      really don't choose to swim with the sharks. At the same time, her
      approachability and lack of arrogance have had to be coupled with a capacity to
      be tougher than she looks. Otherwise, she would not today be the president elect
      of The American Organization of Nurse Executives (AONE). This interview/profile
      will provide an insight into what makes this very hard-working and generous
      spirited lady an exemplary nursing leader.

PMID- 7566206
TI  - Principles, values, and ethics set the stage for managed care nursing.
AB  - Principles, values, and ethics constitute an ethical system that provides nurses
      a context in which to make ethical decisions. As the managed care environment
      generates new ethical issues and intensifies already existing ones, ethical
      education and decision-making skills become even more critical to nursing
      professionals, as well as physicians and hospital administrators.

PMID- 7566207
TI  - Dimensions of the staff nurse role in ambulatory care: Part IV--Developing
      nursing intensity measures, standards, clinical ladders, and QI programs.
AB  - Ambulatory care nurse executives must design valid mechanisms to support new
      models of nursing care delivery. Data from a national survey of practicing
      ambulatory care nurses can assist in this process. Research data can be used as a
      resource for developing ambulatory nursing intensity measures, standards,
      clinical ladders, and quality improvement programming. This is Part IV of a four
      part series.

PMID- 7566208
TI  - Improving staff nurse conflict resolution skills.
AB  - As health care organizations restructure their organizations based on a team
      managed philosophy, staff nurses will need new skills to function successfully in
      this type of environment. Specifically, staff nurses will need improved conflict
      resolution skills. Training and nurse managers' modeling of effective resolution
      techniques are key elements in developing improved conflict resolution skills
      among staff nurses.

PMID- 7566209
TI  - Cost-effectiveness analysis: birth center vs. hospital care.
AB  - Increasingly nursing will need to prove the cost effectiveness of alternative
      models of care. A cost-effectiveness analysis, using a decision analysis format,
      compared a birthing center to a hospital for low-risk deliveries. Results
      indicate that a birth center is a cost-effective model of nursing care.

PMID- 7566210
TI  - Pharmacoeconomics: the nurse manager's challenge.

PMID- 7566211
TI  - Collaborative relationships in the operating room Part II--Hospitals and nurses:
      strategies of partnership.

PMID- 7566212
TI  - Hiring the best talent.

PMID- 7566213
TI  - Managed care safeguards sought by states.

PMID- 7566214
TI  - Successful consulting relationships: the nurse executive and the consultant.
AB  - As hospitals today are faced with numerous health care reform challenges, many
      are seeking the expertise of consulting organizations to help them achieve
      institutional objectives. The successful relationship between the nurse executive
      and the consultant is essential to the organization's ability to achieve defined
      institutional goals. The nurse executive and the consultant have specific roles
      to play and also share some common roles.

PMID- 7566215
TI  - [Listening and observing].

PMID- 7566216
TI  - [Minor symptoms in family medicine; smegma and physiological phimosis].

PMID- 7566217
TI  - [Acute appendicitis: a serious disease in the elderly].
AB  - OBJECTIVE: To determine the differences between acute appendicitis in younger and
      in older patients. DESIGN: Retrospective study. SETTING: Utrecht University
      Hospital and Diakonessen Hospital Utrecht, the Netherlands. METHOD: All patients
      operated in the period 1989-1991 because acute appendicitis was suspected were
      included in this study. The patients were divided into two groups, one fifty
      years of age or older, one younger. Duration of symptoms, histology, closure or
      non-closure of the incision, complications and hospital stay were examined.
      RESULTS: About ten percent of the patients were over fifty years of age (35/366).
      The duration of symptoms in this group was significantly longer. Appendix sana
      occurred less often in the elderly, perforated appendix more often. The wound was
      left open more often in the elderly, but they did not have more complications.
      Their hospital stay, however, was significantly longer. CONCLUSION: The longer
      duration of symptoms and the higher rate of perforation justify a higher place of
      acute appendicitis in the differential diagnosis of acute abdomen in the elderly.
      The more serious course of the disease appears from the longer hospital stay.

PMID- 7566218
TI  - [The Accutrend glucose-cholesterol meter in family practice compared to
      laboratory determinations].
AB  - OBJECTIVE: To determine the similarity in clinical consequences that follow,
      according to the guidelines of the Dutch General Practice Standards, from
      measured glucose and cholesterol concentrations with the Accutrend glucose
      cholesterol meter in general practice on one hand and the usual measurements in a
      laboratory on the other. DESIGN: Comparative study. SETTING: Two general
      practices in the district 'Zuid-Limburg' in the Netherlands. METHOD: 66 patients
      with non-insulin-dependent diabetes mellitus and 34 control patients had their
      capillary blood glucose and cholesterol concentrations measured with the
      Accutrend glucose cholesterol meter. The same measurements were done with
      simultaneously taken venous blood samples, according to usual laboratory methods,
      in a laboratory. The clinical consequences of the measurements in the general
      practice and the laboratory, according to the Standards, were compared and if
      they contained different recommendations they were regarded as clinically
      relevant. RESULTS: In 5% of the cases a clinically relevant difference between
      the glucose measurements done in the general practice and the laboratory was
      found. For the cholesterol measurements a clinically relevant difference was
      found in 18%. Besides, 16% of the cholesterol measurements in the general
      practice were outside the range of the meter. CONCLUSION: The Accutrend glucose
      cholesterol meter is a qualitatively good instrument for blood glucose
      measurements in general practice. For blood cholesterol measurements, the quality
      as well as the range of the meter are still insufficient.

PMID- 7566220
TI  - [Expectant management concerning the breast in 5 patients with occult breast
      carcinoma].
AB  - Five women, between 53 and 78 years old, had axillary lymph node disseminations
      without a primary breast tumour being found at clinical and radiological
      investigations. There is much uncertainty about the treatment to be applied in
      such cases. The patients' breasts were left untreated. One patient had a manifest
      breast tumour after 6 months' follow-up. The other four patients did not show any
      sign of a primary tumour after a median follow-up of 26 months (21-96). An
      expectative policy has already found support in medical literature. The axilla
      should preferably be treated with axillary lymph node dissection.

PMID- 7566219
TI  - [Surgical possibilities in spastic paralysis of arm and hand].
AB  - OBJECTIVE: To determine the results of surgical correction of spastic paralysis
      of the hand due to cerebral palsy. DESIGN: Descriptive. SETTING: Academic Medical
      Centre, Amsterdam, the Netherlands, and rehabilitation centre De Trappenberg.
      METHOD: From 1-1-1990 until 1-6-1994 twenty patients with spastic upper limb in
      cerebral palsy were operated in our hospital. They were all seen preoperatively
      by our multidisciplinary team, and selected according to the Zancolli
      classification. Seventeen operations were aimed at improving hand function, the
      other three were performed for contractures or for cosmetic/hygienic reasons.
      Surgery was aimed at correcting the muscular imbalance, by weakening spastic
      muscles via tenotomy or lengthening and by reinforcing paralysed muscles via
      tendon transfer or rerouting. Often stabilisation of joints by tenodesis,
      capsulodesis or arthrodesis was necessary as well. RESULTS: Eighteen of the
      twenty patients were (very) happy with the results. In two patients there was no
      functional gain. Only once was a postoperative complication seen: pseudarthrosis
      of the first carpometacarpal joint. This was corrected successfully by
      rearthrodesis. We found we were able to predict the functional outcome fairly
      accurately. CONCLUSION: With accurate patient selection, surgical intervention in
      patients with cerebral palsy may restore hand function adequately and
      predictably.

PMID- 7566221
TI  - [The threshold of old age; medical and social care for the older person in the
      Greek-Roman antiquity].

PMID- 7566222
TI  - [Acetylsalicylic acid in acute and postherpetic neuralgia should no be dissolved
      in chloroform].

PMID- 7566223
TI  - [Medical program Memisa in Mugunga Camp, Goma, Zaire, August-October 1994].

PMID- 7566224
TI  - [Familial forms of frontotemporal dementia].

PMID- 7566225
TI  - [Femoral neck fractures in bicyclists due to clipless pedals].

PMID- 7566226
TI  - [Femoral neck fractures in bicyclists due to clipless pedals].

PMID- 7566227
TI  - [Pathophysiology of perinatal asphyxia and brain damage].

PMID- 7566228
TI  - [Should the function of general hospital physician be standardized?].

PMID- 7566229
TI  - [Treatment of keloids of the earlobe].

PMID- 7566230
TI  - [Symptoms of disease and food allergy in children with Down syndrome].
AB  - OBJECTIVE: To obtain an impression of how often parents of children with Down's
      syndrome suspect their children of having a food allergy and what action results
      from this suspicion. DESIGN: Inventorizing controlled descriptive study. 'Zuid
      Holland' in the Netherlands. METHODS: An anonymous questionnaire was sent to 110
      parents of children with Down's syndrome and 223 control parents. RESULTS: The
      parents of children with Down's syndrome reported symptoms of their child which
      might relate to food allergy more frequently than control parents. They reported
      more respiratory disease symptoms (62% and 53% respectively; pneumonia: 22% and
      3%), more gastrointestinal disease symptoms (28% and 17%; constipation or
      diarrhoea: 28% and 13%), but fewer skin disease symptoms (12% and 26%). 34% of
      the parents of Down's syndrome children and 22% of the control parents suspected
      their child of having an allergy and 13% in both groups suspected food to be the
      allergenic responsible. Medical and laboratory investigations were performed in
      37% and 31% and food allergy was diagnosed in 7% and 31% respectively. No
      elimination-reintroduction diet was reported as used for diagnosing. Parents of
      children with Down's syndrome were less satisfied with their consultation of
      health workers. All parents in both groups who suspected their children of having
      a food allergy started an elimination diet, 66% found it had a beneficial effect.
      CONCLUSION: Compared with control parents, parents of children with Down's
      syndrome reported symptoms relating to food allergy more frequently, suspected
      their children of having a food allergy equally often, but had it diagnosed less
      frequently. However, neither group of parents mentioned that an elimination
      provocation test was used for the diagnosis.

PMID- 7566231
TI  - [For which health problems in children is the family physician consulted and how
      often?].
AB  - OBJECTIVE: To determine how often and for what health problems in children
      general practitioners (GPs) are consulted, and whether this is affected by age,
      gender, season, socioeconomic status and degree of urbanisation. DESIGN:
      Descriptive. SETTING: 103 general practices (161 GPs) in the Netherlands. METHOD:
      Data from 63,753 children (0-14 years of age) collected in the framework of the
      Dutch National Survey were used. A random sample of 161 GPs registered all
      contacts between patient and practice during 3 months. Sociodemographic
      characteristics of all practice populations were gathered. Health problems were
      coded according to the International Classification of Primary Care (ICPC).
      Consultation frequency, morbidity presented, age and gender specific incidence
      rates were determined, as well as relative risks of presented morbidity relative
      to sociodemographic characteristics and season. RESULTS: Children consulted a GP
      on average 2.8 times per year. Problems from the respiratory tract (upper
      respiratory tract infection, acute bronchitis, coughing and acute tonsillitis)
      and acute otitis media were presented most. The morbidity varied strongly with
      age. Children from low socioeconomic strata and children living in larger cities
      presented more problems (in particular respiratory and ear problems). CONCLUSION:
      The GP is confronted with a great diversity of health problems in children. The
      variation in consultation frequency and morbidity according to selected
      sociodemographic characteristics showed that presentation of information in more
      detail by age is necessary in order to obtain optimal insight.

PMID- 7566232
TI  - [Standardized multidisciplinary diagnosis of cow's milk protein allergy in
      children. Work Group Cow's Milk Protein Allergy of the Groningen Academic
      Hospital].
AB  - OBJECTIVE: Evaluation of standardized multidisciplinary diagnostic procedures for
      cow's milk allergy (CMA) in children. DESIGN: Prospective standardized study.
      SETTING: Beatrix Children's Hospital, Department of Allergology, Dermatology and
      Dietetics, University Hospital Groningen, the Netherlands. METHODS: From August
      1991 until May 1993, 114 children suspected of CMA for the first time were
      investigated according to the protocol for diagnosis of CMA, together with 23
      children, previously diagnosed as CMA, in whom CMA was re-evaluated. Of 114
      children with first suspicion of CMA, 66 improved on a cow's milk-free diet. The
      remaining 48 were excluded from the study because of no improvement on a cow's
      milk free diet, no diet given, insufficient data or no follow-up. The protocol
      was evaluated by questionnaire sent to 10 representatives of the departments
      involved. RESULTS: In 26/66 (39%) children, the diagnosis of CMA was confirmed by
      cow's milk challenge. The eosinophilic granulocytes were higher (p = 0.04), both
      IgE RAST and Skin Prick Test (SPT) for cow's milk were more often positive (both
      p = 0.01) in CMA than in non-CMA. The sensitivity and specificity were 50%-82%
      for IgE RAST and 60%-84% for the SPT, respectively. Four of the 23 children still
      had CMA at re-evaluation. In three of them, a SPT was performed, which was
      positive in all. In 12 of the 19 children, without CMA at re-evaluation, a SPT
      was performed, which was negative in all. At 1, 2, 3 and 4 years of age 13%, 48%,
      74% and 78%, respectively, of the re-evaluation CMA patients had developed
      tolerance for cow's milk. The use of the protocol was found important by the
      representatives involved, although some practical difficulties remain.
      CONCLUSION: A multidisciplinary approach of CMA is possible. Improvement on a
      cow's milk-free diet by itself is not sufficient to diagnose CMA. Cow's milk
      challenge is obligatory. Laboratory investigations are of limited value. Re
      evaluation of CMA after one year of age is necessary in view of the temporary
      character of CMA. When the SPT for cow's milk is positive, postponement of re
      evaluation may be considered.

PMID- 7566233
TI  - [Pyridoxine-dependent epilepsy in an infant].
AB  - A newborn girl with seizures was, after repeated conventional anticonvulsive
      treatment, cured by pyridoxine administration. Pyridoxine-dependent seizures are
      an uncommon disease with autosomal-recessive heredity and a variable clinical
      picture. The prognosis may be favourable when diagnosis is made early. Confusion
      with perinatal asphyxia, and initial good response to usual anticonvulsive
      treatment can lead to delay in diagnosis.

PMID- 7566234
TI  - [Preferences of residents not in training for a career as general hospital
      physician].

PMID- 7566235
TI  - [The dilemma of 'the final laparotomy'].

PMID- 7566236
TI  - [The dilemma of 'the final laparotomy'].

PMID- 7566237
TI  - [Unusual complications of intravenous drug abuse].

PMID- 7566238
TI  - [Rational use of antibiotics in the neutropenic patient with fever].

PMID- 7566239
TI  - [Psychiatric disorders following heart surgery].

PMID- 7566240
TI  - [Quality of life following coronary surgery and balloon angioplasty; more chest
      pain and social inhibition following angioplasty].
AB  - OBJECTIVE: To determine the differences in quality of life between patients who
      had a coronary artery bypass graft (CABG) and patients who had a percutaneous
      transluminal coronary angioplasty (PTCA). DESIGN: Comparative and prospective
      study. SETTING: Rotterdam, the Netherlands. METHOD: 91 patients with multi-vessel
      coronary disease who had been randomised to CABG (n = 37) or PTCA (n = 54), as
      participants in the CABRI study (Coronary angioplasty or bypass revascularisation
      investigation) completed several psychological questionnaires. Besides, the
      severity of angina pectoris after the procedure was estimated using the Canadian
      Cardiovascular Society score. In a subpopulation of 36 patients (CABG:14;
      PTCA:22) the quality of life just before the intervention was measured, also
      using psychological questionnaires. RESULTS: A significant difference in angina
      pectoris was found between the two groups. The PTCA group experienced more chest
      pain (p < 0.01), at an average of 2.6 years after the intervention. The quality
      of life aspects did not differ between the two groups, except for 'social
      inhibition' (p < 0.05): the PTCA group experienced more problems and had less
      energy (p < 0.01). No significant differences between the PTCA and CABG groups
      were found regarding to the change in quality of life caused by the intervention.
      CONCLUSION: The persistent angina pectoris and social inhibition among patients
      who have had a PTCA need further study.

PMID- 7566241
TI  - [Role of the family physician in the care of chronic psychiatric patients; an
      epidemiological study].
AB  - OBJECTIVE: To determine how many chronic psychiatric patients were treated by
      mental health care institutions, by general practitioners (GPs) or not at all,
      and in the last two groups why there was no contact with mental health care.
      DESIGN: Questionnaire. SETTING: The district 'West-Friesland' in the Netherlands,
      a densely populated rural area. METHOD: GPs and mental health workers checked
      their practice files on the basis of 6 criteria for the number of chronic
      psychiatric patients with or without mental health care contact. RESULTS: The
      response among GPs was 43% and that among mental health institutions almost 100%.
      A prevalence rate of 4.0 per mill was found for chronic mental disorders. On the
      reference date (June 30, 1990) 79% of the chronic psychiatric patients was in the
      charge of mental health care, 15% of GPs, 1% of other institutions and 5% were
      not taken care of (the last percentage was probably underestimated). The support
      the GP gave was of the same frequency as the support of the ambulatory mental
      health care. The three main reasons for support by GPs, without contact with
      mental health care, were patients denying psychiatric problems, patients lacking
      motivation for supplementary help and the possibilities the GPs saw to support
      the patients themselves. CONCLUSION: An important minority of the chronic
      psychiatric patients were supported by a GP only. In half of these cases the GP
      thought he could continue to provide the mental care needed.

PMID- 7566242
TI  - [The Mini Mental Status test inadequate as screening test for cognitive
      deterioration in a neurological department].
AB  - OBJECTIVE: To study the validity of the Mini-mental state (MMS) in a neurological
      population. DESIGN: Comparing the results of a neuropsychological examination and
      the MMS score. SETTING: Departments of Neurology/Neuropsychology of the
      University Hospital Leiden. METHODS: One hundred and forty-seven patients
      participated in the study. One hundred and eight patients were classified into
      two diagnostic groups according to the deterioration index (obtained from test
      results of the neuropsychological examination) and DSM-III-R criteria: 63
      patients had dementia, 45 did not; the other 39 patients were found to have
      specific cognitive impairments and were excluded from the group comparisons. The
      discriminative powers of the deterioration index and the MMS were compared;
      sensitivity and specificity were determined with several cut-off scores of the
      MMS. RESULTS: The MMS had limited power to discriminate between demented and non
      demented patients. The MMS score was strongly related to premorbid intelligence,
      occupational level and age. Increasing the original cut-off score to 25 points
      improved sensitivity and specificity to 79% and 84% respectively (with the
      original cut-off level these were 68% and 93%). CONCLUSION: The diagnostic value
      of the MMS is limited, especially in patients for whom a correct diagnosis is
      most relevant.

PMID- 7566243
TI  - [Heart failure in a Ghanese woman due to endomyocardial fibrosis].
AB  - Endomyocardial fibrosis was diagnosed in a 30-year-old Ghanese woman suffering
      from heart failure and intracardial thrombi. Endomyocardial fibrosis is an
      endemic disease in tropical countries with a high mortality rate. Since the
      aetiology of this disease is still unknown, patients can only be treated
      symptomatically. Endocardial and myocardial damage give rise to reactive
      fibrosis, subendocardial infarction and thrombus formation, resulting in heart
      failure and thromboembolic processes.

PMID- 7566244
TI  - [From the library of the Nederlands Tijdschrift voor Geneeskunde: The anatomic
      atlases of Bernhard Siegfried Albinus].

PMID- 7566245
TI  - [Social and normative aspects of medical technology].

PMID- 7566246
TI  - [HIV infection and AIDS in women and children].

PMID- 7566247
TI  - [Gastroesophageal reflux in infants; recommendations for diagnosis and
      treatment].

PMID- 7566249
TI  - [Leber's optic atrophy; a mitochondrial hereditary disease].

PMID- 7566248
TI  - [Psychiatric medication as risk factor for fatal heat collapse].

PMID- 7566250
TI  - Urinary schistosomiasis in Nebraska.
AB  - Urinary schistosomiasis, a disease caused by the blood fluke Schistosoma
      haematobium, is seen in residents of endemic areas of Africa and Southwest Asia.
      Two cases are described, one in a twelve year old boy and another in a forty-four
      year old man. This type of infection is often indolent but can have significant
      long-term sequelae such as urinary obstruction and bladder cancer. The recent
      increases in U.S. immigration of persons from the areas endemic to
      schistosomiasis behoove physicians to remember this disease when dealing with
      patients native to these lands.

PMID- 7566251
TI  - Prenatal detection of Down syndrome.

PMID- 7566252
TI  - Adolescent and young adult hip dysplasia. The role of Bernese periacetabular
      osteotomy.

PMID- 7566253
TI  - Radiology centennial: the first Nebraska shadows.

PMID- 7566254
TI  - Erythromycin induced torsades de pointes.
AB  - Erythromycin is a widely used antibiotic in today's armamentarium of antibiotics.
      Although erythromycin induced ventricular tachyarrhythmia is rare, this
      potentially life-threatening reaction should be kept in mind. The relative rarity
      of 'torsades de pointes' arrhythmia suggests that other predisposing factors
      contribute to the acquired long QT syndrome. Since more and more macrolide
      products have been approved by the Food and Drug Administration for use in the
      United States, the potential problem with 'torsades de pointes' may exist with
      each of the macrolide antibiotic. Until the exact mechanisms of the arrhythmia
      are worked out, close monitoring of rhythms and QT intervals of high risk
      patients who require erythromycin is certainly advisable. Only a heightened
      awareness among the physicians and medical personnel can the adverse outcome be
      minimized.

PMID- 7566255
TI  - Sexual behavior of Nebraska adolescents.

PMID- 7566256
TI  - Latissimus dorsi transfer for elbow flexion in the paralytic limb.

PMID- 7566257
TI  - Growing up in a socially toxic environment: life for children and families in the
      1990s.

PMID- 7566258
TI  - Social networks and family violence in cross-cultural perspective.
AB  - The purpose of this chapter was twofold. First, the chapter put forward a brief
      cross-cultural perspective indicating that multiple types of intrafamilial
      violence occur cross-culturally. Second, the chapter placed social networks at
      the core of a complex etiology of intrafamilial violence. The purpose of giving
      centrality to social networks is not to suggest that social networks are the sole
      or primary agent contributing to family violence but to broaden the context in
      which family violence is viewed beyond that of the perpetrator, the
      victim/survivor, or the violent dyad.

PMID- 7566259
TI  - Divorce and custody: the rights, needs, and obligations of mothers, fathers, and
      children.

PMID- 7566260
TI  - Epilogue: psychology, law, and the family.

PMID- 7566261
TI  - The deterioration of the family: a law and economics perspective.

PMID- 7566262
TI  - Community, family, and the social good: the psychological dynamics of procedural
      justice and social identification.

PMID- 7566263
TI  - Social or individual orientation? Dilemmas in a post-Communist world.

PMID- 7566264
TI  - Use of unlicensed assistive personnel in the 1990's.

PMID- 7566265
TI  - NLRB decisions favor the SNAs.

PMID- 7566266
TI  - Denouncing cuts, RN groups go public with safety issues.

PMID- 7566267
TI  - Staffing and critical care.

PMID- 7566268
TI  - [Classification and diagnosis of degenerative ataxias].
AB  - The degenerative ataxias comprise a wide spectrum of neurodegenerative diseases
      with varying clinical characteristics and heterogeneous neuropathology.
      Traditionally, classification of these diseases has been based on
      neuropathological criteria. Recently, however, clinical and genetic
      classifications have gained wide acceptance. These classifications distinguish
      between hereditary and non-hereditary ataxias. According to their mode of
      inheritance, the hereditary ataxias are further subdivided into autosomal
      recessive and autosomal-dominant ataxias. The non-hereditary ataxias are divided
      into symptomatic ataxias with an identified cause and idiopathic ataxia with
      unknown cause. Diagnostic criteria based on history, clinical presentation and a
      number of laboratory tests have been defined for each category. More extensive
      ancillary tests are necessary to identify or exclude symptomatic causes of
      ataxia. Recent molecular genetic research has led to the identification of a
      number of gene loci and mutations responsible for certain types of hereditary
      ataxia.

PMID- 7566269
TI  - [Function-controlled neurosurgery. Neurophysiologic and neuropsychological
      monitoring during surgery of the nervous system].
AB  - Neuromonitoring of neural structures has become increasingly common during
      surgery near cortical areas representing sensorimotor and language function
      (epilepsia, tumors), in the brain stem and the spinal cord (tumors), near cranial
      nerves (cerebellopontine angle tumors, trigeminal neuralgia, hemifacial spasm),
      and in the cauda equina (tumors, tethered spinal cord). The technical spectrum to
      monitor these operations includes electrical cortical stimulation to evoke
      sensorimotor phenomena and language disturbances, electroneurography and 
      myography of the cauda equina, motor cranial nerves and nuclei, and
      somatosensory, motor and acoustic evoked potentials. The goals of intraoperative
      neuromonitoring are: (1) minimizing the risk of suffering neurological and
      neuropsychological injury as a result of surgery; (2) extending the surgical
      spectrum to lesions that have previously been considered inoperable or hazardous
      to operate upon; (3) intraoperative electrophysiological documentation that the
      goal of surgery has been achieved; (4) intraoperative basic research.

PMID- 7566270
TI  - [Treatment of ischemic cerebral infarct with glycerine].
AB  - Ischemic brain edema promotes focal cerebral ischemia by increasing intracranial
      pressure and thereby reducing perfusion pressure, obstructing capillaries and
      prolonging transport routes within ischemic tissue. There is clinical and
      experimental evidence that osmotic agents counteract these mechanisms. Moreover,
      glycerol may act as a free radical scavenger, antioxidant, and activator of
      plasma prostaglandin (PGI2), resulting in vasodilation. Improvements in ischemic
      brain energy metabolism after glycerol administration has also been postulated.
      Results of clinical trials on glycerol treatment of acute ischemic stroke were
      not conclusive: some demonstrated improved survival in the acute stage, in others
      survivors benefited in terms of neurological status and/or daily living
      activities. Other trials did not reveal any superiority of glycerol treatment
      over placebo. Glycerol is given intravenously as a 10% solution or orally. By the
      oral route higher intravascular glycerol concentration can be achieved with
      smaller quantities of fluid. Possible side effects include elevation of blood
      glucose level with subsequent lactate acidosis in the ischemic brain, serum
      hyperosmolarity after long-term glycerol administration and--when given
      intravenously--volume overload in patients with congestive heart failure and
      hemolysis that may cause renal failure.

PMID- 7566271
TI  - [Methods for quantifying the onset of arteriosclerotic wall changes in the
      carotid arteries].
AB  - Two different methods of quantifying arteriosclerotically changed vessel walls of
      carotid arteries were compared: the two-dimensional method of measuring intima
      and media thickness (IMT) and the three-dimensional measurement of plaque volume.
      The results of 433 carotid arteries in 174 patients indicate a positive
      correlation in measurements of IMT between internal and common carotid arteries
      (P < 0.001), but no correlation between IMT measurements and three-dimensional
      measurements of plaque volume. For follow-up studies of carotid artery disease
      the three-dimensional volume measurements are the best method of evaluating
      progression or regression of focal plaque volume.

PMID- 7566273
TI  - [Meralgia paraesthetica and its surgical treatment].
AB  - Compression neuropathy of the lateral femoral cutaneous nerve (meralgia
      paresthetica) leads to pain and dysesthesia in the anterolateral thigh. Over a
      period of 23 1/2 years, 29 patients (33 procedures) were operated on after
      failure of conservative treatment: 18 patients (20 procedures) underwent
      neurolysis of the nerve, and in 11 the nerve was transected. The 33 procedures
      were necessary because 1 patient had bilateral meralgia paresthetica and there
      were 3 recurrences with persisting pain. The average follow-up was 32 months
      after neurolysis and 87 months after transection. Complete or partial pain relief
      was found in 72% after decompression and in 82% after transection of the nerve.

PMID- 7566272
TI  - [Anterior interosseus syndrome from the surgical viewpoint].
AB  - An isolated lesion of the anterior interosseus nerve has different causes and may
      be difficult to differentiate preoperatively. However, an exact diagnosis is
      necessary before starting immediate operative therapy or waiting for a change.
      One case of denervation of the flexor pollicis longus muscle is reported. The
      problems involved in clinical and instrumental diagnostic procedures and therapy
      are shown and discussed with reference to the literature.

PMID- 7566275
TI  - [Coping pattern and adjustment in multiple sclerosis].
AB  - A questionnaire (FKV/LIS) was used to study the coping process in 210 patients
      with multiple sclerosis. By cluster analysis of five coping modes, patients could
      be divided into two groups of approximately the same size: cluster 1 presented
      with higher values for "active coping; self-affirmation; religiousness" and lower
      values for "depression" and "trivialization". In cluster 2, on the other hand,
      values were higher for "depression" and "trivialization" whereas values were
      lower for "active coping; self-affirmation; religiousness". Patients in cluster 1
      were significantly more contented with life. Mean age and mean duration of
      illness were higher in cluster 1, suggesting a time-dependent change in the
      coping process with improvement in adaptation in the course of the disease. The
      extent of social support was higher in cluster 1. The consequences for
      psychological intervention are discussed.

PMID- 7566276
TI  - [Syringomyelia, a neglected differential diagnosis in multiple sclerosis. 6 cases
      from a specialty clinic for multiple sclerosis].
AB  - During the last 5 years 11 patients with syringomyelia have been found among 4348
      patients (0.25%) entering our hospital, which specializes in multiple sclerosis.
      Six of these 11 patients had been diagnosed earlier as suffering from multiple
      sclerosis, some of them after a protracted course of neurological illness. In all
      6 patients examination of the cerebrospinal fluid was normal, and visual-evoked
      potentials (VEP) were normal in all but one case, which is described in detail as
      case 2 in this report. Magnetic resonance imaging (MRI) showed a Chiari
      malformation in 3 of 6 syringomyelia patients, who came to us under the diagnosis
      of multiple sclerosis. MRI also showed subcortical white matter lesions in 5 of 6
      patients with syringomyelia. In summary, the diagnosis of multiple sclerosis
      should be reexamined when one of the following signs is present: (1)
      demonstration of Chiari malformation; (2) cerebrospinal fluid is normal; (3)
      visual-evoked potentials are normal. These signs may suggest syringomyelia even
      after years of primary progressive or relapsing remitting development of multiple
      neurological deficits and MRI visible white matter abnormalities.

PMID- 7566274
TI  - [Intrathecal IgG synthesis: when is determination of oligoclonal bands
      necessary?].
AB  - Two quantitative methods of determining the intrathecal synthesis of IgG were
      tested for their usefulness in deciding about the necessity of further
      investigations of oligoclonal bands (OCB) in the CSF. For this purpose, in 2003
      patients with various neurological diseases the intrathecal synthesis of IgG was
      determined by Reiber's formula and by the IgG index, as well as by the
      demonstration of OCB by isoelectric focusing (IEF). While OCB could be detected
      in no patient with an IgG index < 0.45, these bands were always demonstrated in
      patients with an index > 0.80. Even though arrange of 0.45-0.8 OCB was only
      detected in 268/1316 patients (20.4%), in 190/268 samples (70.8%) OCB were the
      only criterion for intrathecal synthesis of IgG. Calculation of intrathecal
      synthesis of IgG by Reiber's formula was less helpful in deciding about the
      necessity for IEF. Even though they had no intrathecal synthesis of IgG, as
      calculated by Reiber's formula, 189/1472 patients (12.8%) had OCB in the CSF. OCB
      were always detected if local production of IgG was > 12%. In patients with a
      severe damage of the blood-CSF barrier, calculation of the IgG index gave more
      false-positive results than calculations using Reiber's formula.

PMID- 7566278
TI  - [Atypical entrapment syndrome of the distal suprascapular nerve of the incisura
      scapulae. Case report and overview of the literature].
AB  - Entrapment neuropathy of the suprascapular nerve is a rare disease of the
      peripheral nerve system. Of Mumenthaler's 3465 patients with peripheral nerve
      lesions, only 15 had suprascapular nerve damage. Since Thompson's and Kopell's
      first description of suprascapular entrapment neuropathy in 1959, some reports
      have been published. In the majority of cases the lesion is normally located in
      the suprascapular notch with clinical involvement of the supra- and infraspinatus
      muscle. Here we report on an uncommon lesion of the suprascapular nerve with
      sparing of the supraspinatus muscle in a volleyball player. The current
      literature will be reviewed. The anatomical basis, examination, differential
      diagnosis and therapy of this type of entrapment neuropathy will be discussed.

PMID- 7566277
TI  - [Interventional closure of an open foramen ovale in a patient with recurrent
      cerebral ischemia].
AB  - In a 24-year-old female patient suffering from recurrent ischemia, an aneurysm of
      the atrial septum and a patent foramen ovale with significant right-to-left shunt
      during the Valsalva maneuver were detected by means of contrast Doppler
      echocardiography. After other causes had been excluded, paradoxical embolism was
      suspected to be the cause of the cerebral symptoms. The defect was closed by a 17
      mm Rashkind occluder without complications. Six months later no residual shunt
      was detected and no further neurological event had occurred. This case
      demonstrates the feasibility of non-operative closure of those defects. This new
      technique could represent an alternative to long-term anticoagulation or
      operative procedures in selected patients.

PMID- 7566279
TI  - [Oral, low-dosage methotrexate in chronic progressive multiple sclerosis. A
      preliminary critical analysis].

PMID- 7566280
TI  - The role of N-acetylcysteine in the treatment of chronic obstructive pulmonary
      disease.

PMID- 7566281
TI  - Idiopathic haemochromatosis: magnetic resonance signal intensity ratios permit
      non-invasive diagnosis of low levels of iron overload.
AB  - OBJECTIVE: The detection of low levels of iron overload by magnetic resonance
      imaging. METHODS: Eight consecutive patients suspected of having idiopathic
      haemochromatosis. Comparison of signal intensity ratios and absolute iron content
      of liver. RESULTS: There was a good correlation between the signal intensity
      ratios and iron content in the range 2-30 micrograms Fe/mg dry weight.
      CONCLUSIONS: The ability of a non-invasive technique to detect low levels of iron
      overload could be useful in the assessment of therapy and in the screening of
      relatives of probands with idiopathic haemochromatosis.

PMID- 7566282
TI  - Fever of unknown origin (FUO): report on 53 patients in a Dutch university
      hospital.
AB  - BACKGROUND AND METHODS: Data on patients with fever of unknown origin (FUO) show
      that the problem of FUO differs, depending on place and time. To obtain a better
      insight into FUO in the Netherlands, we performed a retrospective study in our
      University Hospital. RESULTS: We studied 53 patients fulfilling FUO criteria.
      Infection was found in 11 patients (21%), neoplasms in 10 cases (19%), non
      infectious inflammatory diseases in 12 patients (23%). In 16 patients (30%) no
      diagnosis could be made. In 12 patients fever subsided. In 4 patients fever
      persisted with a median follow-up of 14.5 years. In all 5 patients without
      directional clues no diagnosis could be made. In 21 patients (57%) the diagnosis
      was found by non-invasive methods, in 16 patients (43%) invasive methods were
      necessary. A median of 54 investigations were done in all patients. CONCLUSIONS:
      The spectrum of FUO is changing. The proportion of patients in whom no diagnosis
      can be made is growing. The presence of directional clues seems to be an
      important issue, which other series often do not mention. Their importance should
      be studied in a larger, prospective study. The use of sophisticated diagnostic
      techniques seems to be extensive. Because very little is known about the
      diagnostic yield of many of those techniques, a prospective study on this aspect
      is needed.

PMID- 7566283
TI  - Nephroptosis: a considerable cause of renovascular hypertension.
AB  - Four females were admitted with hypertension. Other causes of hypertension were
      excluded on clinical grounds. Digital substraction angiography performed in 3
      patients revealed no stenosis of the renal arteries. The 99mTc-Mag3 renogram
      showed diminished perfusion and excretion on the affected side. Right-sided
      nephropexy was performed in all 4 cases via lumbotomy after which all 4 patients
      became normotensive. We conclude that nephroptosis is a considerable cause of
      renovascular hypertension and deserves particular attention in cases of possible
      renovascular hypertension when angiography shows no stenosis. We also conclude
      that renography is the preferred diagnostic method in the diagnosis of
      renovascular hypertension due to nephroptosis.

PMID- 7566284
TI  - Treatment of visceral leishmaniasis in a patient with AIDS with antimony and
      gamma-interferon: remission and prevention of relapse by maintenance therapy with
      weekly pentamidine.
AB  - A 41-year-old AIDS patient with fever, nightly perspiration, diarrhoea, anaemia
      and leukopenia was diagnosed as having visceral leishmaniasis (VL). After 8 weeks
      of antimony treatment combined with gamma-interferon, given in 2 courses of 3 and
      5 weeks, 12 weeks apart, the bone marrow revealed no parasites by microscopy and
      culture. Parasitic DNA could still be demonstrated by polymerase chain reaction.
      Weekly intravenous pentamidine maintenance therapy seemed to prevent relapses.
      Over time the patient was treated for disseminated M. avium infection, CMV
      retinitis, porphyria cutanea tarda and renal tubular acidosis. Ultimately he
      succumbed, 2.5 years after the diagnosis of VL and 4.5 years after the diagnosis
      of AIDS was established.

PMID- 7566285
TI  - Phaeochromocytoma in various disguises.
AB  - Patients with phaeochromocytoma may present a broad spectrum of clinical
      manifestations as presented here in 5 case reports. Pathophysiology, clinical
      management, pharmacotherapy and associated diseases are discussed. Although
      catecholamine measurements in both urine and blood as well as modern localisation
      techniques are valuable adjuncts to establishing the diagnosis, a high index of
      suspicion remains the key to this diagnosis.

PMID- 7566287
TI  - Intervention research.

PMID- 7566286
TI  - Early detection and treatment of oesophageal and gastric cancer. The Rotterdam
      Oesophageal Tumour Study Group.
AB  - Early oesophageal and gastric cancer are unique forms of oesophageal and gastric
      carcinoma with an excellent prognosis. Remarkable changes have taken place in the
      epidemiology of upper gastrointestinal malignancies. In particular, the incidence
      of adenocarcinoma of the distal oesophagus and the gastric cardia has risen over
      the past two decades. In the United States and Europe, early detection is
      dependent on a low threshold for upper gastrointestinal endoscopy with biopsy,
      because specific symptoms and physical findings are rarely present in patients
      with early oesophageal and gastric cancer. In addition to histology, the
      detection of possible markers of malignancy, such as aneuploidy (detected by flow
      cytometry) and the presence of oncogenes and tumour-suppressor genes, in biopsy
      material may be of value in the diagnosis of early cancers. For patients with
      early oesophageal or gastric cancer, surgery offers the best hope of cure. If
      patients are at high risk for surgery, an endoscopic resection may be an
      alternative option. This review discusses the definitions, the changes in
      epidemiology, the current options for diagnosis and treatment, and the value of
      screening programs for patients with early oesophageal or gastric cancer.

PMID- 7566288
TI  - Hantavirus nephropathy in The Netherlands: clinical, histopathological and
      epidemiological findings.
AB  - Until 1995, 39 cases of serologically confirmed hantavirusnephropathy in humans,
      caused by the Puumala type of Hantavirus, have been documented in the
      Netherlands. Thirty-two of these occurred in Twente, a small region in the
      eastern part of the country, in which the presence of Puumala-like Hantavirus in
      feral rodents has recently been demonstrated. Sixteen of the cases documented in
      humans occurred in 1993. Here we present an overview of clinical,
      histopathological and epidemiological findings of hantavirus infections. All the
      clinical and laboratory findings of the 39 documented cases were similar to those
      found in infections with the same virus in neighbouring countries. Complete
      recovery of renal function occurred in all patients. One patient developed a
      Guillain-Barre syndrome after having recovered from her renal failure.
      Histopathological examination of kidney biopsies collected from 13 of the
      patients in the acute stage, confirmed the presence of acute interstitial
      inflammation of differing severity in these individuals. A serological survey
      carried out amongst 4232 healthy blood donors in the endemic area showed a
      seroprevalence of 0.7%. This suggests that less severe or perhaps even
      subclinical infections occur.

PMID- 7566289
TI  - Non-coeliac sprue possibly related to methotrexate in a rheumatoid arthritis
      patient.
AB  - We describe a case of non-coeliac sprue in a low-dose methotrexate treated
      patient suffering from rheumatoid arthritis. This is the first case report of
      this possibly reversible complication of methotrexate therapy. The diagnosis was
      confirmed by a duodenal mucosal biopsy revealing the characteristic intestinal
      histopathology of coeliac sprue. After discontinuation of the drug a repeat
      biopsy was almost normal, and completely normal after reintroduction of a normal
      diet. One could speculate about the methotrexate related mechanism of the villous
      atrophy: it might be either a direct toxic effect or a secondary effect of the
      immunosuppression.

PMID- 7566291
TI  - Successful recovery of a patient with thallium poisoning.
AB  - We describe a patient suffering from protracted and life-threatening thallium
      poisoning. She was treated with Prussian blue and forced diuresis, and made a
      good recovery. Cisapride may be effective in improving gastric emptying and
      relieving constipation resulting from the thallium and the treatment.
      Haematological abnormalities occurred in the early phase of the poisoning, with a
      prolonged fall in the CD4/8 lymphocyte ratio during recovery.

PMID- 7566290
TI  - Total hemiatrophy as a rare presentation of linear scleroderma .
AB  - Scleroderma rarely presents as total hemiatrophy of one side of the body. A 63
      year-old patient is discussed with progressive facial hemiatrophy and with
      atrophy of skin, subcutaneous tissue, muscle and bone tissue of one side of the
      body, complicated by ocular and neurological manifestations.

PMID- 7566292
TI  - Endocrine aspects of obesity.
AB  - A review is presented of the endocrine status in human obesity. The effect of
      changes in nutrient intake or body weight and the use of weight-reducing drugs on
      endocrine systems are discussed. There are several endocrine abnormalities found
      in obese patients. However, these altered endocrine functions seem secondary to
      the obese state and do not play a role in the pathogenesis of obesity. Some of
      these abnormalities are, at least partially, responsible for the development of
      complications related to the obese state. Weight reduction in general is followed
      by normalization of endocrine functions. The pharmacological agents used in the
      treatment of obesity do not influence the endocrine systems significantly.

PMID- 7566293
TI  - Risk and prognosis.

PMID- 7566294
TI  - Insulin analogs: the virtual reality of normal insulin secretion.

PMID- 7566295
TI  - Urinary prostaglandin and prostaglandin metabolite excretion in patients with
      essential hypertension or hypertension with renal artery stenosis.
AB  - BACKGROUND: Recent studies have reported elevated prostaglandin levels in
      patients with renal artery stenosis and hypertension. To investigate whether a
      distinction between essential hypertension and hypertension with renal artery
      stenosis is possible by measuring eicosanoid excretion, we studied the excretion
      of these compounds in patients with essential hypertension and in hypertensives
      with concomitant renal artery stenosis. METHODS: The 24-h urinary excretion of
      metabolites of prostaglandin I2, prostaglandin E2 and metabolites of thromboxane
      A2 was sampled under standardised conditions, in 15 patients with essential
      hypertension and in 15 patients with unilateral renal artery stenosis with
      hypertension. Also clinical and biochemical characteristics of the subjects were
      analysed. RESULTS: The patients with renal artery stenosis had significantly
      lower excretion of prostaglandin I2 than did the essential hypertensive patients.
      However, the overlap in the values was large, thus not allowing a diagnostic
      differentiation according to urinary prostaglandin I2 levels. The excretion of
      prostaglandin E2 and of metabolites of thromboxane A2 showed no significant
      differences among the groups. CONCLUSIONS: Measurement of urinary prostaglandin
      or prostaglandin metabolite excretion did not contribute to the non-invasive
      detection of the presence of a renal artery stenosis in the patients in this
      study.

PMID- 7566296
TI  - Recommendations for treatment of symptomatic hyponatremia.

PMID- 7566297
TI  - Eicosanoids and renal allograft rejection.
AB  - The role of eicosanoids as mediators of inflammation in the course of renal
      allograft rejection is reviewed. Elucidation of their particular roles has come
      from the use of specific inhibitors, and one looks forward to their application
      in human transplant management. As illustrated by the experience with the use of
      fish oils, additional benefit over that of standard immunosuppression is
      anticipated but quantitating that benefit in individuals may not be easy.

PMID- 7566298
TI  - Comparison of Lp(a) concentrations and some potential effects in hemodialysis,
      CAPD, transplantation, and control groups, and review of the literature.
AB  - Apolipoprotein (a)-Lp(a)-is reported to be an independent risk factor for
      coronary artery disease and for hemodialysis (HD) access occlusion. Homology with
      plasminogen may predispose to thrombosis. High concentrations usually have been
      reported in patients on HD and on continuous ambulatory peritoneal dialysis
      (CAPD), but near-normal values in many kidney transplants (TP). We used Pharmacia
      immunoradiometric assay in 52 patients on HD, 58 on CAPD, 94 after TP, and 56
      controls. The Lp(a) mean levels for CAPD, HD, TP, and control groups were 738,
      647, 348, and 368 U/l and the medians were 542, 537, 96 and 143 U/l,
      respectively. The means and medians for CAPD and HD were significantly greater
      than those for TP and controls (p < 0.003 for means and < 0.005 for medians). We
      found no significant difference between: (1) Lp(a) means or medians comparing HD
      and CAPD or TP and controls; (2) Lp(a) means for the 33 patients with insulin
      dependent diabetes mellitus and the 171 without; (3) number of occlusions of HD
      fistulae or grafts in patients with high Lp(a) values and without; (4) mean Lp(a)
      for CAPD patients on gemfibrozil and also for TP patients on 3-hydroxy
      methylglutaryl coenzyme 1 reductase inhibitors, or diet alone, before and after
      treatment, and (5) mean Lp(a) values for HD and CAPD patients with and without
      myocardial infarction. Lp(a) did not correlate significantly with fractional
      shortening or left ventricular end systolic or diastolic diameter by
      echocardiogram or with ejection fraction. For TP patients, Lp(a) and serum
      creatinine correlated (p = 0.004), and mean Lp(a) for 71 TP on ciclosporin A
      exceeded that for the other 23 patients (p < 0.03). Lp(a) fell in 13 of 14
      patients after TP (mean fall 77%). The dominant Apo(a) isoform in 10 of 13
      patients on CAPD or HD with high Lp(a) values was the equivalent of S2
      (Utermann). Lp(a) in HD or CAPD is often elevated and regulated by both genetic
      and renal failure factors, but falls after TP with return of renal function and
      mainly genetic regulation. Lp(a) was not a risk factor for coronary artery
      disease in HD or CAPD patients and did not fall significantly with two drugs or
      diet.

PMID- 7566299
TI  - Diagnostic revolution of microhematuria by real time confocal scanning laser
      microscope: Hyodo-Iino-Miyagawa method, third report.
AB  - The real time confocal scanning laser microscope provides excellent three
      dimensional images free of out-of-focus information. The objective of this study
      was to evaluate the usefulness of the laser microscope for the diagnosis of
      microhematuria. Characteristics of the test were evaluated in 81 patients with
      definite causes of hematuria. 30 erythrocytes in urinary sediments were examined
      for each patient, and those in whom less than 20% of the erythrocytes were
      poikilocytes were considered to have urological diseases and those in whom 80% or
      more of the erythrocytes were poikilocytes to have nephritis. According to these
      criteria, the sensitivity and the specificity of the examination to nephritis
      were 100 and 98.1%. 91.4% of the patients with urological disease had the
      nonglomerular type. The time required for the examination was less than 2-5 min
      in samples containing 1-3 erythrocytes in one field under an ordinary light
      microscope (x400).

PMID- 7566300
TI  - The risk of occupational exposure to blood and body fluids for health care
      workers in the dialysis setting. Italian Multicenter Study on Nosocomial and
      Occupational Risk of Infections in Dialysis.
AB  - In 1991, to assess the risk of occupational exposure to blood or other body
      fluids in health-care workers (HCWs) working in the dialysis setting, properly
      trained interviewers used standardized questionnaires asking the 583 HCWs
      employed in 19 Italian dialysis units to recall exposures sustained in the
      previous year. On a total of 208,498 dialyses performed in the previous year, 105
      (5 per 10,000 dialyses) needlesticks, and 579 (28 per 10,000 dialyses)
      skin/mucous membrane contaminations were recalled. Recapping injuries were
      recalled in 38 cases (1.8 per 10,000 dialyses), but 67 needlestick injuries (4.1
      per 10,000 dialyses) occurred during other circumstances (p = 0.006). The highest
      rate of skin/mucous membrane contaminations were recalled during the dialysis
      patient care, but more than one third of exposures occurred in other
      circumstances (break in blood circuit, disposal, contamination with blood-soiled
      equipment. To minimize the risk of occupational exposure to blood efforts must
      continue to increase compliance with Universal Precautions; moreover, needle
      designs incorporating safety features to prevent sticks are needed.

PMID- 7566301
TI  - High-risk surgical acute renal failure treated by continuous arteriovenous
      hemodiafiltration: metabolic control and outcome in sixty patients.
AB  - The outcome and metabolic control was studied in 60 critically ill patients with
      acute renal failure (ARF) treated by continuous arteriovenous hemodiafiltration
      (CAVHD) in a single surgical intensive care unit. Mean age (+/- SEM) was 60 +/- 2
      years with a male predominance (80%). The majority of patients required
      mechanical ventilation (83%) and/or vasopressor support (70%) and suffered from
      multiorgan failure [mean number of organ system failures 3.3 +/- 0.3 (range 1
      6)]. CAVHD resulted in a rapid decline of serum urea and creatinine levels during
      the first 72 h (urea 47.4 +/- 2.3 to 30.3 +/- 1.4 mmol/l, p < 0.05, and
      creatinine 572 +/- 27 to 361 +/- 23 mumol/l, p < 0.05); thereafter, controlled
      steady-state levels were achieved with serum urea levels kept below 30 mmol/l
      with full protein alimentation and often despite hypotension, surgery and
      septicemia. Significant electrolyte derangements could be easily corrected and
      maintained within normal limits. Bicarbonate homeostasis could be restored within
      48 h in patients with severe metabolic acidosis (HCO3- < 20 mmol/l) with use of
      bicarbonate as a buffering anion (17 +/- 0.5 to 23.2 +/- 0.6, p < 0.05). CAVHD
      allowed rapid removal of excess body and lung water (up to 5 liters/day) without
      hemodynamic instability. Despite a mean pretreatment APACHE II score of 26.5, 26
      patients (43%) survived until discharge from the intensive care unit, of whom 23
      (38%) survived to leave hospital. Requirement of mechanical ventilation or
      vasopressor support, higher APACHE II scores and septicemia were all associated
      with a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566302
TI  - Oral activated charcoal in patients with uremic pruritus.
AB  - Twenty-three chronic uremic patients on maintenance hemodialysis and suffering
      from severe pruritus were treated with activated powdered charcoal (6 g daily
      p.o.). In 10 patients pruritus disappeared completely, and in 10 other patients a
      partial effect was observed. The favorable results persisted for several weeks
      after discontinuation of the treatment. Only 3 cases were totally unresponsive.
      No relevant undesirable side effects were observed with the exception of 1 case
      who showed treatment intolerance. It is concluded that activated charcoal per os
      is a safe, effective, and low-cost therapy for patients with uremic pruritus, but
      its mechanism of action is unknown.

PMID- 7566303
TI  - No acute change of serum erythropoietin in response to hypocalcemia or
      antihypertensive agents in uremic patients.
AB  - Endogenous erythropoietin (EPO) secretion can still be modulated in patients with
      end-stage renal failure but only in response to strong stimuli. Thus even
      anephric dialysis patients are able to increase EPO production acutely when
      exposed to a marked hypoxic stimulus. The present study was designed to test the
      hypothesis that a decrease of plasma calcium or the administration of various
      antihypertensive agents might be able to induce acute changes of plasma EPO
      concentration. Four groups of chronic hemodialysis patients were studied. Eight
      patients volunteered for the induction of an acute, transient hypocalcemia via a
      calcium-free dialysate during the initial 60 min of a regular dialysis session of
      240 min. Plasma immunoreactive (i) EPO, total calcium, and intact parathyroid
      hormone (iPTH1-84), as well as blood ionized calcium and blood gases were
      measured before as well as 30, 60, 120 and 240 min after the start of dialysis.
      In addition, plasma iEPO was measured 48 h after the session. Patients of group 2
      (n = 6), group 3 (n = 6), and group 4 (n = 7) received the day after a
      hemodialysis session a single dose of either acetazolamide, furosemide, or
      enalapril, respectively, and their plasma iEPO was determined before and 3, 6
      and/or 24 h after drug administration. In group 1, plasma total calcium decreased
      from 2.39 +/- 0.07 mM (mean +/- SEM) to 1.98 +/- 0.02 and 1.83 +/- 0.03 mM after
      30 and 60 min of dialysis, respectively, and blood ionized calcium from 1.28 +/-
      0.04 to 1.02 +/- 0.03 and 0.92 +/- 0.04 mM, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7566304
TI  - Decreased uroporphyrinogen decarboxylase activity in patients with end-stage
      renal disease undergoing hemodialysis.
AB  - Raised plasma uroporphyrin levels were found in all the 14 patients with end
      stage renal disease studied, 7 of whom were on continuous ambulatory peritoneal
      dialysis (CAPD) and 7 on hemodialysis (HD). The elevation observed in the HD
      group was higher than that noted in the CAPD group; 18-fold in the former and 13
      fold in the latter. The difference in uroporphyrin plasma levels between the two
      dialysis populations might be explained, at least partially, by the reduced
      activity of uroporphyrinogen decarboxylase (UROD), the enzyme which converts
      uroporphyrinogen to coproporphyrinogen. A decrease of 48% was noted in the HD
      group, whereas no change was observed in the CAPD group. A significant negative
      correlation (r = -0.37, p < 0.01) was found between the concentration of
      uroporphyrin in plasma and the activity of UROD. In view of the data shown, it is
      suggested that erythrocyte UROD activity should be interpreted with caution in HD
      patients suspected of having porphyria cutanea tarda.

PMID- 7566305
TI  - Effect of nifedipine on the renal functional reserve in cyclosporine-treated
      renal-transplant recipients.
AB  - Cyclosporine decreases renal perfusion and impairs the renal hemodynamic response
      to a protein load. High-dose nifedipine has been shown to elevate renal plasma
      flow (RPF). We measured the renal functional reserve of 6 cyclosporine-treated
      renal-transplant recipients following intravenous administration of an amino acid
      solution, before and 2 weeks after therapy with high-dose nifedipine (up to 120
      mg/day). Pretreatment renal functional reserve was nil Following administration
      of nifedipine, RPF increased by 22% (p < 0.01), filtration fraction decreased by
      14% (p < 0.005) and renal vascular resistance declined by 39% (p < 0.005). Renal
      functional reserve remained unchanged. High-dose nifedipine increases renal
      perfusion but does not restore renal functional reserve in cyclosporine-treated
      renal-transplant recipients.

PMID- 7566306
TI  - Elevated serum pepsinogens in chronic renal failure patients.
AB  - Human pepsinogens, the precursors of pepsin, originating from the stomach mucosa,
      are classified into two biochemically distinct groups, namely pepsinogen I (PG I)
      and pepsinogen II (PG II). We studied the serum levels of PG I and II in 51
      normal volunteers, 23 chronic glomerulonephritis patients, 21 continuous
      ambulatory peritoneal dialysis (CAPD) patients and 40 hemodialysis patients.
      Serum pepsinogen levels were measured with a competitive binding double antibody
      radioimmunoassay. In the group of chronic glomerulonephritis patients, a positive
      correlation between the serum creatinine and the pepsinogen levels were found.
      The serum pepsinogen levels were remarkably elevated in CAPD and hemodialysis
      patients. The median levels of post-hemodialysis PG I (265.4 +/- 165.2 ng/ml) and
      PG II (41.7 +/- 38.0 ng/ml) were significantly higher than prehemodialysis values
      (PG I 207.4 +/- 127.5 ng/ml, PG II 29.0 +/- 16.6 ng/ml). Pepsinogen release by
      isolated gastric glands of guinea pigs was suppressed by guanidinosuccinic acid
      and was facilitated by calcium. The data suggest that both removal of
      guanidinosuccinic acid and infusion of calcium during hemodialysis contribute to
      the raised serum levels of these pepsinogens after hemodialysis.

PMID- 7566307
TI  - Bone marrow transplant nephropathy: radiation nephritis revisited.
AB  - Late-onset renal failure occurs in up to 20% of survivors of bone marrow
      transplantation. Total body irradiation is a major factor in this syndrome, so
      called bone marrow transplant nephropathy (BMT NP), which is defined by
      disproportionate anemia, hypertension, and azotemia. Previous or concurrent
      chemotherapy may potentiate the effect of radiation on the kidney. Kidney
      function may decline acutely or more gradually, with eventual long-term
      stabilization. Patient survival is associated with control of the blood pressure.
      BMT NP is a recognized complication of bone marrow transplantation, which will
      require ongoing attention.

PMID- 7566308
TI  - Lack of influence of recombinant human erythropoietin on parathyroid function in
      hemodialysis patients with secondary hyperparathyroidism.
AB  - The effects of recombinant human erythropoietin (rHuEPO) treatment on parathyroid
      function in patients on maintenance hemodialysis (HD) with secondary
      hyperparathyroidism (HPT) is poorly understood. We compared the levels of serum
      intact parathyroid hormone (PTH) and the suppressibility of PTH by intravenous
      calcium infusion before and after 12 weeks of rHuEPO treatment in 8 HD patients
      with secondary HPT. The suppressibility of PTH by calcium infusion in HD patients
      was also compared with that of normal subjects. After rHuEPO treatment, in HD
      patients hematocrit and hemoglobin levels increased significantly from 20.1 +/-
      1.3% and 6.65 +/- 0.46 g/dl to 28.7 +/- 1.0% and 9.68 +/- 0.39 g/dl,
      respectively. The serum intact PTH levels did not change significantly (541.9 +/-
      65.3 pg/ml before versus 572.9 +/- 75.3 pg/ml after rHuEPO treatment), nor did
      serum ionized calcium, phosphate, magnesium, aluminum, alkaline phosphatase, and
      1.25(OH)2D levels. Calcium infusion significantly increased serum ionized calcium
      and suppressed serum PTH levels. However, the increment in serum calcium levels
      and the percent decrement of serum PTH showed no significant differences before
      and after rHuEPO treatment in HD patients. Elevations in serum calcium levels
      during calcium infusions were not significantly different between normal subjects
      and HD patients. However, the percent maximal decrement in serum PTH level was
      less in HD patients both before and after rHuEPO treatment than in normal
      subjects (-75.4 +/- 3.9 and -76.4 +/- 4.1% versus -91.4 +/- 1.4%). We conclude
      that rHuEPO treatment has no influence on parathyroid function in maintenance HD
      patients with secondary HPT. In addition, PTH secretion is less suppressed by
      calcium infusion in the same group of patients.

PMID- 7566309
TI  - Morphine enhances deposition of ferritin-antiferritin complexes in the glomerular
      mesangium.
AB  - Since increased mesangial accumulation of matrix has been considered to be an
      important event in the development of focal glomerulosclerosis, we investigated
      whether morphine, an active metabolite of heroin, can modulate mesangial
      accumulation of immune complexes. Control or morphine-dependent rats were
      administered intraperitoneal ferritin (8 mg/100 g body weight) daily for 6 weeks.
      Body weight, blood pressure, serum creatinine, 24-hour urinary protein and
      creatinine excretion rates were measured at 3-week intervals. Rats were
      sacrificed at the end of 6 weeks and kidney tissue was studied by light,
      immunofluorescence and electron microscopy. Serum creatinine levels and urinary
      protein excretion rates were not different between control and morphine-dependent
      rats. All morphine-dependent rats developed hematuria, whereas only 1 control rat
      developed hematuria. Light microscopy revealed no proliferation of mesangial
      cells and only a minimal increase in the mesangial matrix. Electron-microscopic
      studies showed deposition of immune complexes in the mesangial region. Mesangial
      cells showed aggregation of ferritin in lysosomes. Immunofluorescence studies
      revealed the presence of IgG staining predominantly in the mesangial region. The
      majority (60%) of morphine-dependent rats showed a diffuse mesangial deposition
      of IgG when compared to control rats (83%) who showed only focal deposition.
      These results indicate that morphine enhances deposition of immune complexes in
      the mesangium. Morphine-induced matrix but may also change its quality. This may
      play a pathogenic role in the development of glomerular lesions in patients who
      abuse opiates.

PMID- 7566310
TI  - Potassium depletion potentiates amphotericin-B-induced toxicity to renal tubules.
AB  - Hypokalemia and potassium depletion are frequent complications of amphotericin B
      therapy. Both ischemic and gentamicin-induced renal failure is potentiated by
      potassium depletion; it is, therefore, possible that amphotericin B
      nephrotoxicity is similarly influenced. This study evaluated whether the acute
      nephrotoxic response to amphotericin B is potassium sensitive. Potassium-depleted
      and control rats were subjected to an acute intravenous infusion of either
      amphotericin B (AmB-K; AmB, n = 10 in each) or its vehicle (V-K, V; n = 6 in
      each). Potassium-depleted rats had both lower urinary daily excretion and lower
      plasma levels of potassium than control animals (0.1 +/- 0.0 vs. 2.1 +/- 0.2
      mEq/day, p < 0.001, and 3.8 +/- 0.2 vs. 1.9 +/- 0.1 mEq/l, p < 0.001,
      respectively). In AmB and AmB-K groups, there were equivalent falls in glomerular
      filtration rate and renal blood flow, and a rise in renal vascular resistance,
      compared with V and V-K. In contrast, the AmB-K group showed a higher urinary
      excretion of sodium (AmB-K vs. AmB: 2.9 +/- 0.7 vs. 1.1 +/- 0.3 microEq/min; p <
      0.05) and fractional excretion of Na (AmB-K vs. AmB: 1.6 +/- 0.4 vs. 0.6 +/-
      0.1%; p < 0.05) in comparison to the AmB group. Neither of these parameters
      changed in either amphotericin B or vehicle-treated groups. These results suggest
      that potassium depletion does not influence the acute renovascular effects of
      amphotericin B but potentiates its tubular toxicity. This may have clinical
      implications since hypokalemia and potassium depletion are frequent complications
      of amphotericin B therapy.

PMID- 7566311
TI  - Prevention of enhanced parathyroid hormone secretion, synthesis and hyperplasia
      by mild dietary phosphorus restriction in early chronic renal failure in rats:
      possible direct role of phosphorus.
AB  - In order to evaluate the effect of dietary phosphorus (P) restriction on the
      pathogenesis of secondary hyperparathyroidism (2 degrees HPT) in chronic renal
      failure (CRF), we studied parathyroid function and parathyroid cell proliferation
      in 5/6 nephrectomized rats (CRF rats) fed with three different dietary P contents
      (0.6, 0.3 and 0.1%). Four weeks after 5/6 nephrectomy, serum immunoreactive
      parathyroid hormone (PTH) concentration, PTH mRNA level in parathyroid glands and
      the size of parathyroid glands were increased in CRF rats compared to those of
      sham-operated rats when both groups of rats were fed with normal P (0.6%) diet.
      These changes were not accompanied by any detectable changes of serum
      concentrations of calcium (Ca), inorganic phosphate (Pi) or calcitriol. In
      contrast, such evidence of 2 degrees HPT was obliterated in CRF rats fed with 0.3
      or 0.1% P diet. In rats fed with 0.3% P diet, serum concentrations of Ca, Pi, and
      calcitriol were not different from those of sham-operated rats or from CRF rats
      fed with normal P diet. In contrast, serum Ca and calcitriol concentrations
      increased and serum Pi decreased in CRF rats fed with 0.1% P diet. These data
      suggest that 2 degrees HPT can be completely prevented at the levels of PTH
      secretion, synthesis and parathyroid cell proliferation by mild dietary P
      restriction (0.3%) alone, and that such effects may not depend upon the changes
      in serum concentrations of Ca, Pi or calcitriol, but may depend on reduced
      dietary P content per se. Thus, mild dietary P restriction from the early stage
      of CRF may be clinically effective for the prevention of 2 degrees HPT.

PMID- 7566312
TI  - Effect of ketanserine in cyclosporine-induced renal dysfunction in rats.
AB  - Cyclosporine (CsA)-treated female Wistar rats, in dose of 37.5 microM (45
      mg)/kg/day for 7 days, exhibited significantly decreased creatinine clearance
      (Ccr), and provoked body weight loss (BWL), which is consistent with the
      development of nephrotoxicity (NT). Urine volume (V) did not change and
      proteinuria (PU) was not provoked. These changes were associated with
      significantly diminished ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2
      excretions. Light-microscopic (LM) sections of rat kidneys showed that all
      kidneys were affected but the lesions (mainly diffuse vacuolization) were
      reversible. When CsA-treated animals were pretreated with ketanserine (KTS),
      which antagonizes (a) the direct vasoconstrictor effect of serotonin (5-HT), and
      (b) the amplifying effects of 5-HT on other vasoactive substances (such as
      noradrenaline (NA), alpha 1-receptors, histamine, H2 receptors, and prostaglandin
      F2 alpha), Ccr and urine volume significantly increased, BWL was partially
      prevented and the ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 excretions
      were significantly enhanced. LM sections showed that only 5 of 9 rats were
      affected but the lesions were of less importance. These observations indicate
      that the NT induced by CsA in our studies was mediated by 5-HT, a potent
      vasoconstrictor agent, and by the metabolites of arachidonic acid. However, other
      vasoactive agents and additional mechanisms could also be implicated.

PMID- 7566314
TI  - A case with nephrophthisis complex or a variant of the disease.

PMID- 7566313
TI  - Hereditary osteo-onycho-renal dysplasia with excess urinary pyridinoline cross
      links and abnormal kidney collagen cross-linking.
AB  - HOOD syndrome is a rare genetic disorder also known as nail patella syndrome.
      Biochemical and molecular biological data are rare and not conclusive.
      Preliminary data suggest the involvement of collagen type IV. This would,
      however, not be enough to explain nail or bone involvement. As kidney pathology
      would be consistent with a cross-linking disorder, we tested collagen IV and
      kidney collagen cross-linking on SDS-PAGE. This method showed a remarkable
      reduction in high-molecular-weight collagen polymers. The patient's and his
      mother's urinary pyridinoline cross-link excretion was manifold increased.
      Disturbed cross-linking of connective tissue proteins would help to explain the
      multiorgan involvement.

PMID- 7566315
TI  - Successful pregnancy in a hemodialysis patient treated with erythropoietin.

PMID- 7566316
TI  - Serum apolipoprotein profile of renal-transplant patients.

PMID- 7566317
TI  - Bowel perforation associated with continuous ambulatory peritoneal dialysis.

PMID- 7566318
TI  - Ehlers-Danlos syndrome with reflux nephropathy.

PMID- 7566319
TI  - Erythrocyte aggregation before and after haemodialysis.

PMID- 7566321
TI  - Dysfunction of myoplasmic Ca2+ regulation in skeletal muscle from predialytic
      uremic patients.

PMID- 7566320
TI  - Cyclosporine neurotoxicity in a renal-transplant recipient.

PMID- 7566322
TI  - [Cavernous sinus tumors. 45th Annual Congress of The Neurosurgical Society of the
      French languages. Buenos Aires, Argentina, 17-20 September 1995. Proceedings].

PMID- 7566323
TI  - [Malformative intraspinal lipomas. 45th Annual Congress of The Neurosurgical
      Society of the French Languages. Buenos Aires, Argentina, 17-20 September 1995.
      Proceedings].

PMID- 7566324
TI  - [Glomerulopathies with organized immunoglobulin deposits].

PMID- 7566325
TI  - [Bone involvement in idiopathic calcium lithiasis].
AB  - Bone involvement in idiopathic calcium nephrolithiasis is characterized by the
      following abnormalities: a) the bone density is decreased, the severity of bone
      loss being dependent upon the existence of hypercalciuria and upon the
      pathophysiology of this latter: it is inconsistent in the absence of
      hypercalciuria or when hypercalciuria is of the absorptive type I or II, whereas
      it is almost constant in fasting hypercalciuria without secondary
      hyperparathyroidism and constant and severe in the rare true renal
      hypercalciuria. b) The bone histology (which has been evaluated only in
      idiopathic hypercalciuric patients) mainly shows a defect in bone formation at
      the exception of the rare renal hypercalciuria. Osteoclastic hyperresorption is
      only seen in this latter type of hypercalciuria whereas in the other types of
      hypercalciuria only an increase of the total or inactive resorption surface is
      observed. This phenomenon is possibly explained only by a delayed refilling of
      the resorption lacunae secondary to the decreased bone formation. The osteoid
      thickness is either normal or decreased despite decrease in mineralization
      apposition rate which seems therefore to be secondary to the decreased bone
      formation. c) Symptomatic bone disease in hypercalciuric stone formers is
      exceptional and always related to a severe long term calcium restriction. d) The
      biochemical markers of bone resorption tend to be increased in idiopathic
      hypercalciuria. Hydroxyprolinuria is more often elevated than pyridinolinuria.
      However pyridinolinuria is negatively correlated to bone density. The contrast
      between the increase of these bone resorption markers and the usual normality of
      plasma PTH and of the osteoclastic resorptive surfaces, suggest the role of meat
      induced acid load which may favor inactive resorption by dissolution of bone
      buffers. A disturbed profile synthesis of cytokines which induce differentiation
      and proliferation of the osteoclasts and which modulate the osteoblastic
      proliferation and function (IL-1, IL-6, TNF-alpha, GM-CSF...) may play a role in
      the bone loss of calcium stone formers but further studies are necessary to
      precise its transient or permanent involvement in their bone disease. e) The
      decrease of bone formation may be explained by the suppressed PTH secretion which
      may be explained by hypercalcitriolemia. This excess of calcitriol synthesis may
      be secondary either to monocyte increased synthesis of IL-1 which stimulates the
      renal 1 alpha-hydroxylase by the mean of an increased PGE2 synthesis or to the
      relative hypophosphatemia of the calcium stone formers comparatively to healthy
      controls. Hypercalcitriolemia may originate from the activated monocyte itself.
      The decrease in bone formation may also be secondary to the action of monokines
      on the osteoblast differentiation and/or function.

PMID- 7566326
TI  - ["The Dialybre card". The minimum portable dialysis medical record. Results of
      the development phase].
AB  - Dialybre is the research study on portable minimum medical records related to
      patients treated by hemodialysis. It uses the chip card, a new technology which
      makes relationships between health practitioners and patients easier. Since 1992,
      it is broadcasted in 15 hemodialysis centers. Evaluation of the development phase
      shows that despite its advantages, the chip card is not much used for the
      following reasons: usage not yet fully understood, lack of coherence in the
      computerized hospital information system, not enough card readers which are very
      costly, and a cultural lack of trust in any new technology. There is, more over,
      extra work involved for entering data in "Logidial" (computerized medical
      records) from where "Dialybre" is automatically updated.

PMID- 7566327
TI  - [Extra-capillary proliferation complicating the development of an extramembranous
      idiopathic glomerulonephritis].
AB  - Occurrence of crescentic formation superimposed to idiopathic membranous
      glomerulopathy worsens severely its prognosis with evolution to end stage renal
      disease. We report the case of a 65 years old man with nephrotic idiopathic
      membranous glomerulopathy who subsequently developed an acute renal failure
      secondary to crescentic formation. Pulse of high dose methylprednisolone
      administration improved renal function. Seven similar observations are analysed
      and pathogenic mechanisms discussed.

PMID- 7566328
TI  - [The DEC-205 receptor expressed by dendritic cells and thymic epithelial cells is
      implicated in antigen processing].

PMID- 7566329
TI  - [Mechanism of glomerular filtration failure after renal ischemia in man].

PMID- 7566330
TI  - [Effects of the invalidation of inducible nitric oxide synthase gene].

PMID- 7566331
TI  - [Inactivation of the angiotensin I conversion gene: different effects according
      to sex on fertility and arterial pressure].

PMID- 7566332
TI  - The Schmitt Symposium: The Cytoskeleton and Alzheimer's Disease. Proceedings.
      Rochester, New York, May 21-23, 1994.

PMID- 7566333
TI  - The microtubule cytoskeleton and the development of neuronal polarity.
AB  - The concept that axons and dendrites represent a fundamental polarization of the
      nerve cell has been borne out by numerous morphological, functional, and
      molecular studies. How does polarity arise during development? We and others have
      focused on the role of the microtubule cytoskeleton because microtubules (a) are
      essential components of axons and dendrites; (b) possess an inherent polarity at
      the molecular level; (c) are regulated by interactions with microtubule
      associated proteins (MAPs), some of which have polarized distributions in mature
      neurons. Here we review data on the initial acquisition of polarity as observed
      in neuronal culture and roles for microtubules and MAPs in this morphogenetic
      event. We present data clarifying some previously conflicting results on tau
      localization during the establishment of polarity and provide new evidence that
      phosphorylation of tau is spatially regulated during the development of polarity
      in culture. Elucidation of mechanisms locally regulating tau phosphorylation
      during normal neuronal development may provide clues to the significance of its
      abnormal phosphorylation in Alzheimer's disease.

PMID- 7566334
TI  - Mechanisms of neuronal polarity.
AB  - Polarity is intrinsic to neuronal function. The somatodendritic domain receives
      and decodes incoming information and the axonal domain delivers information to
      target cells. Progressive loss of neuronal polarity is a major histopathological
      event in neural aging and neurodegenerative diseases, like Alzheimer's disease,
      preceding death and disappearance of nerve cells. Our laboratory is interested in
      the study of the pathways and mechanisms by which neuronal membrane polarity is
      established and maintained. Due to the lack of appropriate polarized neuronal
      cell lines for biochemical analysis, the molecular mechanisms underlying this
      phenomenon remain obscure. We use a neuronal culture system, hippocampal neurons
      from rat embryos, in which polarity is established in vitro, and the scientific
      rationale and experimental strategies proven useful in understanding the
      mechanisms of epithelial polarity. Here we review our own work on neuronal
      membrane polarity. The reader interested should consult any of the excellent
      reviews published recently (7,27,31,43).

PMID- 7566335
TI  - Networking with proline-directed protein kinases implicated in tau
      phosphorylation.
AB  - Proline-directed kinases such as the mitogen-activated protein (MAP) kinases,
      cyclin-dependent protein kinase 5 (CDK5) and glycogen synthase 3 (GSK3) have been
      implicated in the hyperphosphorylation of the tau protein associated with
      Alzheimer's disease. Such aberrant phosphorylation of tau appears to compromise
      on its ability to bind to and stabilize microtubules, and this may contribute to
      Alzheimer's disease pathology. In this review, the architecture of the
      intracellular signal transduction pathways that regulate proline-directed kinases
      is described. The MAP kinases serve as major intersection points in the flow of
      information from a plethora of extracellular stimuli and affect diverse cellular
      processes that are often important for cell proliferation. Although brain
      contains terminally differentiated neurons, many of the known components of MAP
      kinase-dependent lines of communication are highly expressed in the nervous
      system. Similar signalling pathways may also regulate CDK5 and GSK3. In mitotic
      cells, abnormal activation of the protein kinase network at multiple points can
      contribute to oncogenic transformation. It is proposed that Alzheimer's disease
      may also result from accumulated defects in the kinase network that governs the
      proline-directed kinases such that their inappropriate activation is sustained in
      the affected neurons. A detailed understanding of proline-directed kinase
      dependent pathways may permit the identification of rational targets for the
      therapeutic intervention of Alzheimer's disease and other neurological disorders.

PMID- 7566336
TI  - Structure, function, and regulation of neuronal Cdc2-like protein kinase.
AB  - We have identified and purified from bovine brain a novel protein kinase which
      catalyzes in vitro phosphorylation of neurofilament proteins NF-H and NF-M and
      tau proteins at sites implicating the enzyme in the regulation of
      neurocytoskeleton dynamics and in Alzheimer pathology. The protein kinase
      displays a phosphorylation site specificity similar or identical to the cell
      cycle regulatory kinase, cdc2 kinase. The purified kinase is a heterodimer of a
      cdc2-like catalytic subunit, called cdk5, and a 25 kDa regulatory subunit. The
      regulatory subunit is essential for kinase activity, and it is derived from a 35
      kDa protein, p35 by proteolysis. Northern blot analysis of tissue distribution
      indicates that cdk5 is widely distributed but especially rich in brain, whereas
      p35 expression is only found in brain. The protein kinase is therefore termed
      neuronal cdc2-like kinase. The neuron-specificity of the enzyme appears to be
      conferred by the regulatory subunit. During cell division, cdc2 kinase is
      regulated by complex phosphorylation mechanisms involving a network of specific
      protein kinases. Some of these kinases or their homologs have been found in
      mammalian brains and they may be involved in the regulation of neuronal cdc2-like
      kinase.

PMID- 7566337
TI  - Staging of Alzheimer's disease-related neurofibrillary changes.
AB  - Specific immunocytochemical methods (AT8) permit evaluation of neuronal changes
      well before the actual formation of neurofibrillary tangles and neuropil threads.
      Initial changes are found in the transentorhinal region (temporal lobe). From
      here the destructive process encroaches upon the entorhinal region, Ammon's horn,
      and neocortex. Initial changes occur in comparatively young individuals and can
      also be observed at the same predilection sites in a few species of old aged
      domestic animals. In a later state of destruction, AT8 immunoreactive neurons
      develop typical argyrophilic neurofibrillary tangles and neuropil threads. Six
      stages of disease propagation can be distinguished with respect to the location
      of the tangle-bearing neurons and the severity of changes (transentorhinal stages
      I-II: clinically silent cases; limbic stages III-IV: incipient Alzheimer's
      disease; neocortical stages V-VI: fully developed Alzheimer's disease). Whole
      mount techniques reveal the lesional pattern of the particularly severely
      involved superficial entorhinal layer as seen from the free surface of the
      parahippocampal gyrus. This approach facilitates recognition of even subtle
      pathologic changes throughout the entire extent of cortical territories such as
      the transentorhinal and entorhinal regions.

PMID- 7566338
TI  - Correlations of synaptic and pathological markers with cognition of the elderly.
AB  - It has been suggested that the physical basis for dementia is structural or
      functional loss of synapses. To confirm this finding, we performed an enzyme
      linked immunoassay (ELISA) with a monoclonal antibody (EP10) to a synaptophysin
      like protein in brain samples from 45 prospectively studied elderly subjects with
      an average age of 83.3 +/- 10.1 years. We compared the synaptic marker to
      immunoreactivity with a newly developed PHF antibody (TG3). The cases were
      selected on the basis of availability of frozen tissue, and included subjects
      ranging from clinically normal to end-stage dementia. As an initial assessment,
      we determined Pearson product moment correlations for two clinical measures--the
      Blessed test of information, concentration, and memory (BICM) and the Fuld object
      Memory Evaluation (FOME)--with ELISA data and with traditional pathologic
      markers. We found strong correlations (p < 0.01-0.001) for BICM with brain
      weight, neuronal loss in the basal nucleus of Meynert (nbM), counts of senile
      plaques (SP) in the neocortex and hippocampus, and neurofibrillary tangles (NFT)
      in all areas except the parahippocampal cortex. Except in the occipital lobe,
      where paired helical filament changes are relatively uncommon, TG3
      immunoreactivity also correlated strongly with BICM. Weak correlations (p < 0.05)
      were found for BICM with EP10-immunoreactivity in only the temporal and parietal
      lobes. Only the pathologic variables showed any significant correlations with
      FOME. Because inclusion of normal subjects with few or no pathologic lesions
      could have been driving the strong correlations with pathologic markers, we
      limited the analysis to those subjects with dementia (BICM; 8). After making this
      correction, EP10-immunoreactivity in all cortical areas and the hippocampus
      correlated better (p < 0.05-0.01) with BICM but not FOME. The present univariate
      analysis suggests that synaptic markers may not be the best structural correlate
      of dementia and that markers indicative of cytoskeletal changes, e.g., SP, NFT
      and PHF protein accumulation, may be better correlates of dementia in the
      elderly.

PMID- 7566339
TI  - Functional alterations in neural circuits in Alzheimer's disease.
AB  - While a correlation exists at the regional level between the distribution of
      neurofibrillary tangles and the predicted sites of brain dysfunction based on
      clinical and functional neuroimaging studies, the relationship between
      neurofibrillary tangles and neuronal dysfunction is poorly understood. Using
      cytochrome oxidase activity as a marker of neuronal functional activity, we found
      reductions in metabolic activity both in a hippocampal subfield with a high
      density of neurofibrillary tangles (CA1) as well as in subfields relatively
      spared (CA3, dentate granule cells). In contrast, we found no reduction in
      activity in primary visual cortex. Using in situ hybridization, we found a
      selective reduction in a mitochondrial-encoded cytochrome oxidase mRNA transcript
      with sparing of a nuclear-encoded transcript. These results suggest that the
      reduction in cytochrome oxidase activity in Alzheimer's disease brain may be
      related to an alteration in mitochondrial gene expression. The absence of a
      direct correlation between structural pathology and cytochrome oxidase activity
      suggests that neurons that remain structurally intact in Alzheimer's disease may
      nonetheless undergo substantial changes in metabolic activity.

PMID- 7566340
TI  - Neurons bearing neurofibrillary tangles are responsible for selected synaptic
      deficits in Alzheimer's disease.
AB  - The observation that neurons containing neurofibrillary tangles are usually
      adjacent to neurons free of any morphological indication of disease, suggests the
      hypothesis that it is NFT-bearing neurons that are primarily responsible for the
      loss of function in AD. Quantitative Golgi postmortem studies from our
      laboratories have indicated that there is in many regions of the brains of
      nondemented humans an age-related increase in dendritic extent of single neurons.
      In Alzheimer's disease, this normal, age-related increase in dendritic extent was
      not found, leading to the hypothesis that one of the neurobiological defects in
      AD is a failure of neuronal plasticity. Message levels of the growth-associated
      protein, GAP-43, in frontal association cortex (area 9/46) indicated that AD
      brains with the highest density of neurofibrillary tangle-bearing neurons, showed
      GAP-43 message levels decreased of the order of 6-fold relative to AD brains with
      the lowest density of NFT. Combined immunocytochemistry to differentiate tangle
      bearing from tangle-free neurons with in situ hybridization to define relative
      GAP-43 message levels in single neurons revealed that grain density over tangle
      bearing neurons containing nuclei was reduced 3-fold compared to that over
      adjacent tangle-free neurons. This reduction in expression of GAP-43 message in
      tangle-bearing neurons was selective, because using probes for other messages
      showed that grain density over tangle-bearing neurons was, on average, increased
      or similar to that over adjacent non-tangle-bearing neurons. Message levels for
      the synaptic vesicle-associated protein, synaptophysin, have also been found to
      be reduced in tangle-bearing neurons relative to adjacent tangle-free
      neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566341
TI  - Ultrastructure of neurofibrillary tangles in the cerebral cortex of sheep.
AB  - Recently, we reported that neurofibrillary tangles (NFTs) of the Alzheimer type
      develop in the cerebral cortex of aged sheep (Ovis aries). In the current study,
      we utilized light and electron microscopic immunocytochemistry to describe in
      greater detail the characteristics of sheep NFTs during early stages of
      neurofibrillary degeneration. We investigated neurons that were stained using the
      monoclonal antibody Alz-50 and that contained relatively small numbers of paired
      helical filaments (PHFs). Serially cut ultrathin sections were evaluated to take
      maximal advantage of ultrastructural resolution. At the light microscope level,
      we observed preferential localization of Alz-50 immunoreactive accumulations at
      dendritic branch points in early NFTs. A similar staining pattern was observed
      using the monoclonal antibody AT8 which recognizes a phosphorylated epitope on
      tau. Ultrastructurally, we found that Alz-50 staining at dendritic branch points
      was associated with clusters of ribosomes. The focal deposition of phosphorylated
      tau proteins at dendritic branch points may indicate a link between the initial
      stages of neurofibrillary pathology and specific cytoskeletal alterations that
      involve dendritic remodeling. Neurons that contained relatively small numbers of
      PHFs appeared otherwise healthy with regard to their cytoskeleton and organelles.

PMID- 7566343
TI  - Relationship between plaques, tangles, and dystrophic processes in Alzheimer's
      disease.

PMID- 7566344
TI  - On the structure of microtubules, tau, and paired helical filaments.
AB  - Microtubules and their associated proteins form the basis of axonal transport;
      they are degraded during the neuronal degeneration in Alzheimer's disease. This
      article surveys recent results on the structure of microtubules, tau protein, and
      PHFs. Microtubules have been investigated by electron microscopy and image
      processing after labeling them with the head domain of the motor protein kinesin.
      This reveals the arrangement of tubulin subunits in microtubules and the shape of
      the tubulin-motor complex. Tau protein was studied by electron microscopy,
      solution X-ray scattering, and spectroscopic methods. It appears as an elongated
      molecule (about 35 nm) without recognizable secondary structure. Alzheimer PHFs
      were examined by FTIR and X-ray diffraction; they, too, show evidence for
      secondary structure such as beta sheets.

PMID- 7566342
TI  - Molecular dissection of the paired helical filament.
AB  - Abundant neurofibrillary tangles, neuropil threads and plaque neurites constitute
      the neurofibrillary pathology of Alzheimer's disease. They form in the nerve
      cells that undergo degeneration in the disease where their regional distribution
      correlates with the degree of dementia. Each lesion contains the paired helical
      filament (PHF) as its major fibrous component. Recent work has shown that PHFs
      are composed of the microtubule-associated protein tau in a hyperphosphorylated
      state. PHF-tau is hyperphosphorylated on six adult brain tau isoforms. As a
      consequence, tau is unable to bind to microtubules and is believed to self
      assemble into the PHF. Current evidence suggests that protein kinases or protein
      phosphatases with a specificity for serine/threonine-proline residues play an
      important role in the hyperphosphorylation of tau. Candidate protein kinases
      include mitogen-activated protein kinase, glycogen synthase kinase-3 and cyclin
      dependent kinase 5, whereas the trimeric form of protein phosphatase 2A is a
      candidate phosphatase.

PMID- 7566345
TI  - Tau domains, phosphorylation, and interactions with microtubules.
AB  - We consider the interactions of tau protein with microtubules from two points of
      view, phosphorylation and domain structure. Tau can be phosphorylated at many
      sites and by several kinases, notably by proline-directed kinases (MAPK, GSK-3,
      cdk5) which generate Alzheimer-like antibody epitopes. Other kinases
      phosphorylate Ser 262, a site that has a particularly pronounced influence on the
      affinity of tau for microtubules. All of these sites can be cleared by
      phosphatases PP-2a and calcineurin. The site Ser262 lies within the repeat domain
      of tau. However, when probing the domains of tau for their effects on microtubule
      binding, nucleation, assembly, or bundling, the repeat domain has only a weak
      influence. Whereas the repeat domain of tau binds to microtubules with low
      affinity, repeat-less tau binds strongly yet unproductively in terms of
      microtubule assembly. Productive binding of tau to microtubules depends on the
      combination of (some) repeats with the flanking regions, as if the flanking
      regions acted as "jaws" for the proper positioning of tau on the microtubule
      surface.

PMID- 7566346
TI  - Hyperphosphorylation of tau in PHF.
AB  - Tau in PHF is known to be highly phosphorylated and immunochemical study has
      indicated the similarity of the phosphorylation between PHF-tau and fetal tau. We
      have determined the exact phosphorylation sites in both PHF-tau and fetal rat tau
      by ion-spray mass spectrometry and sequencing of ethanethiol-modified peptides.
      In PHF-tau, 19 sites have been identified; all the phosphorylation sites except
      for Ser-262 are localized to the amino- and carboxyl-terminal flanking regions of
      the microtubule-binding domain. Half of them are shared by fetal tau. Thus, PHF
      tau is much more phosphorylated. Whereas most of the sites in fetal tau are
      proline-directed, half of them in PHF-tau are nonproline-directed. Overall, the
      hyperphosphorylation of PHF-tau can be considered to consist of fetal-type
      phosphorylation and additional proline-directed and nonproline-directed
      phosphorylation. This extraphosphorylation may provide PHF-tau with the unusual
      characteristics including assembly incompetence.

PMID- 7566347
TI  - Alzheimer neurofibrillary lesions: molecular nature and potential roles of
      different components.
AB  - Neurofibrillary lesions found in Alzheimer disease (AD) are known to react with
      antibodies raised against different molecules. At least 20 components have been
      detected in neurofibrillary tangles. These components can be roughly categorized
      into five groups, which include structural proteins, kinases and other cytosolic
      enzymes, stress-related molecules, amyloid and amyloid binding proteins, and
      others. Among them, an abnormal form of microtubule associated protein tau, PHF
      tau, is a major component of Alzheimer NFT. Kinases associated with NFT,
      especially those belonging to the family of proline-directed Ser/Thr kinases, are
      considered to be important for PHF-tau hyperphosphorylation. A potentially
      significant kinase is a Cdc2-related kinase, which is associated tightly with
      paired helical filaments, has a molecular weight of 33kDa and is different from
      other known Cdc2-related kinases. The possibility that some of the NFT-associated
      elements may play an active role in the pathogenesis of Alzheimer's disease was
      supported by recent studies, in which advanced glycated products and markers of
      oxidant stress were located in NFT. In addition, PHF-tau was found to be
      glycated, and in vitro glycated tau was capable of inducing oxidant stress.
      Further characterization of different components of NFT by biochemical and other
      approaches will be important for understanding the mechanisms involved in the
      supramolecular aggregation of PHF within NFT.

PMID- 7566349
TI  - Secreted beta-APP stimulates MAP kinase and phosphorylation of tau in neurons.
AB  - We have previously demonstrated that the secreted form of the beta-amyloid
      precursor protein (beta-APP) activates mitogen-activated protein (MAP) kinases in
      PC-12 pheochromocytoma cells. beta-APP as well as other treatments that activate
      MAP kinase also enhance phosphorylation of the microtubule-associated protein tau
      in these cells. In this study, we extended this analysis to neurons. Using
      dissociated cultures of cortical neurons, we found that exposure to beta-APP
      activated MAP kinase 4 and 7 days but not 1 day after plating. Phosphorylation of
      tau in neurons was measured by immunoreactivity with the AT8 antibody, which
      recognizes a phosphorylated epitope present in tau from paired helical filaments.
      We found that activation of MAP kinase in neurons was associated with increased
      amounts of AT8-reactive tau. These results support a role for MAP kinase in
      transducing the biological effects of secreted beta-APP on neurons and suggest
      possible mechanisms by which beta-APP might be involved in the pathogenesis of
      Alzheimer's disease.

PMID- 7566348
TI  - Modulation of PHF-like tau phosphorylation in cultured neurones and transfected
      cells.
AB  - Two cellular systems have been used to investigate the modulation of tau
      hyperphosphorylation. In the first system, the effects of the excitatory amino
      acid glutamate, the microtubule destabilising agent colchicine, and beta 25-35
      amyloid peptide on tau phosphorylation were studied in rat cortical neurones in
      primary culture. Using immunocytochemistry and western blot analysis, we
      demonstrated that tau in these cultures is normally highly phosphorylated, but a
      proportion becomes rapidly dephosphorylated following treatment of the cultures
      with glutamate or colchicine. These changes in tau phosphorylation occurred prior
      to cell death. In the second system, the ability of p42 MAP and p44 MAP kinases,
      glycogen synthase kinases 3 alpha and 3 beta (GSK-3 alpha and GSK-3 beta) to
      phosphorylate tau in transfected COS cells was investigated. Both GSK-3 alpha and
      GSK-3 beta phosphorylated tau to produce a PHF-like state of phosphorylation but
      the MAP kinases failed to induce such a transformation in tau. These results
      suggest that aberrant regulation of GSK-3 alpha/beta may be a pathogenic
      mechanism in Alzheimer's disease.

PMID- 7566350
TI  - Quantitative analysis of tau protein in paired helical filament preparations:
      implications for the role of tau protein phosphorylation in PHF assembly in
      Alzheimer's disease.
AB  - In Alzheimer's disease, there is a major redistribution of the tau protein pool
      from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal
      tau by acid reversible occlusion of a generic tau epitope in the tandem repeat
      region and characteristic sedimentation in the if-II protocol developed in this
      laboratory. We show that 85% of tau bound in the PHF-like configuration can be
      recovered in the if-II PHF-fraction. Less than 1% of this material was
      phosphorylated at the mAb AT8 site in aged clinical controls or in cases with
      minimal or mild dementia. Of tau phosphorylated at the mAb AT8 site, only 12% was
      found to co-sediment with PHFs. These low levels could not be explained by
      postmortem dephosphorylation. As more than 95% of PHF-tau is not phosphorylated,
      even at early stages of pathology, it is misleading to use the terms "PHF-tau"
      and "phosphorylated tau" as though they were synonymous, particularly as this
      implies a pathogenetic role which phosphorylation need not have.

PMID- 7566351
TI  - Examination of phosphorylated tau protein as a PHF-precursor at early stage
      Alzheimer's disease.
AB  - Hyperphosphorylated tau protein which can be isolated on the basis of
      insolubility in 1% sarkosyl (A68-tau fraction) is thought to represent a
      precursor pool for PHF assembly, associated histologically with neuritic
      pathology, which feeds into a more resistant tangle-associated PHF pool via cross
      linking and proteolysis. We examined these predictions at the earliest detectable
      stages of neurofibrillary pathology. We report that there is no evidence that
      neuritic pathology represents an early pathologic stage, no evidence of an
      association between neuritic pathology and phosphorylated tau, no evidence of
      selective accumulation of phosphorylated tau at early stages of pathology, and no
      evidence for a precursor/product relationship between phosphorylated tau and PHFs
      during progression of pathology. We conclude that altered phosphorylation is a
      secondary process affecting 5% of PHFs and does not explain PHF assembly in
      Alzheimer's disease.

PMID- 7566352
TI  - Degenerative and protective signaling mechanisms in the neurofibrillary pathology
      of AD.
AB  - Attention has focussed on the molecular alterations in neurofibrillary tangles
      (NFT) in Alzheimer's disease (AD) with the presumption that the events leading to
      the alterations are involved in the neurodegenerative mechanism. Here I propose
      that some of the manifestations of NFT result from activation of neuroprotective
      signaling cascades such as those induced by neurotrophic factors. Increasing data
      implicate free radicals and calcium in the mechanism of neuronal injury
      (including cytoskeletal pathology) and death in AD. Increased accumulation of
      beta-amyloid peptide (A beta), reduced energy availability, and increased
      oxidative processes are among the age-associated changes in AD that appear to be
      upstream to increases in cellular free radicals and calcium. Neurotrophic factors
      influence the expression of gene products known to stabilize calcium homeostasis,
      suppress free radical accumulation, and protect neurons against AD-relevant
      insults. The events leading to the cytoskeletal alterations in NFT are not clear
      although some of the alterations can be induced by excitotoxic and metabolic
      insults. On the other hand, kinases activated by neurotrophic factors may
      contribute to tau hyperphosphorylation during brain development and in AD.
      Activities in both degenerative and protective signaling pathways are subject to
      modification by aging, and by genetic and environmental factors, suggesting that
      the multiple cytoskeletal alterations in NFT probably result from concurrent
      activation of both neurodegenerative and neuroprotective cascades.

PMID- 7566353
TI  - Neuronal kinase stimulation leads to aberrant tau phosphorylation and
      neurotoxicity.
AB  - Neurofibrillary tangles in Alzheimer's disease brain consist mainly of abnormally
      phosphorylated tau proteins organised in paired helical filaments. Induction of
      tau phosphorylation in living neurons by hyperstimulation is monitored by
      specific monoclonal antibodies, such as AT-8 and PHF-1. By quantitative
      immunocytochemistry, we show that aberrant phosphorylation at the Ser199/Ser202
      epitope (AT-8) and at the Ser 396 epitope (PHF-1) are moderately induced,
      proportionally to the degree of kinase stimulation. Whereas AT8 expression is
      prominent after 48 h, cell death becomes significant at 72 h and is related to
      the degree of stimulation and the expression level of aberrant tau
      phosphorylation. Time-lapse videomicroscopy of individual neuroblastoma cells
      suggest that hyperstimulation leads to a form of morphological over
      differentiation. Immediately before cell death, some cells tend to display some
      features of mitosis. The data suggest a strong correlation between the expression
      of specific PHF-epitopes and subsequent cell death. The extended time scale of
      toxicity in this model may be appropriate to study in more detail the steps
      leading to aberrant phosphorylation associated neurotoxicity.

PMID- 7566355
TI  - Mice overexpressing the human neurofilament heavy gene as a model of ALS.
AB  - We discuss the evidence, based on the analysis of transgenic mice overexpressing
      the human neurofilament (NF) heavy gene, that abnormal NF accumulations can
      provoke neurodegeneration of motor neurons. Transgenic mice overexpressing by two
      fold the normal levels of human NF-H proteins develop a progressive motor neuron
      disease with several pathologic features reminiscent of those found in
      amyotrophic lateral sclerosis (ALS). A plausible mechanism for the selective
      motor neuron degeneration is that exceeding levels of NF-H cross-linkages impede
      transport of newly synthesized NF structures. The abnormal NF accumulations in
      perikarya and proximal axons is accompanied by a disruption in axonal transport
      of not only NF proteins but also of other components required for maintenance of
      axons. The relevance of the NF-H transgenics as a model of ALS is discussed in
      light of our current knowledge of motor neuron disease.

PMID- 7566354
TI  - Presence of tau in isolated nuclei from human brain.
AB  - Previous studies have demonstrated that the microtubule-associated protein (MAP)
      tau is present in the axonal and somatodendritic compartment of neurons. In
      cultured primate cell lines, tau has been found localized to the NOR regions of
      the acrocentric chromosomes in mitotic cells and the dense fibrillar regions of
      nucleoli in interphase cells. We report here the presence of nuclear tau in
      nuclei isolated from fresh, frozen human frontal cortex. Using several monoclonal
      antibodies against tau, Tau-1, Tau 46.1, and 5E2, we have established by both
      indirect immunofluorescence and Western blotting that tau is an integral
      component of nuclei isolated from Alzheimer's disease (AD) and pathologically
      normal control brains. Brain nuclear tau, like nuclear tau in primate cells, is
      insoluble in SDS and must first be extracted with formic acid prior to analysis
      by Western blot. Immunoblot analysis of isolated brain nuclei displays the
      characteristic ladder of tau proteins and demonstrates that all isoforms of tau
      are present. It is unclear whether levels of nuclear tau can be correlated to
      pathologic events in AD, but its insoluble nature along with reports of
      intranuclear PHFs warrant further studies of nuclear tau as a molecular candidate
      in the genesis of AD.

PMID- 7566356
TI  - Role of axons in membrane phospholipid synthesis in rat sympathetic neurons.
AB  - The axonal synthesis of phospholipids has been demonstrated in compartmented
      cultures of rat sympathetic neurons. In this model of neuron culture, metabolic
      events occurring in distal axons were studied independently of those occurring in
      cell bodies. Using radiolabeled tracers the axonal biosynthesis of the major
      membrane phospholipids and fatty acids but not cholesterol was detected. The
      capacity of axons for synthesis of phosphatidylcholine (PC), the major membrane
      lipid, was confirmed by the demonstration that key enzymes of PC biosynthesis
      were present in distal axons. A double-labeling experiment showed that at least
      50% of axonal PC was synthesized locally in axons, with the remainder being made
      in cell bodies and transported into axons. The requirement of axonal PC synthesis
      for axonal elongation was investigated. When PC biosynthesis in distal axons
      alone was inhibited by two independent approaches (deprivation of choline or
      addition of the inhibitor hexadecylphosphocholine) axonal growth was markedly
      retarded. Our experiments demonstrated that PC synthesis in cell bodies was
      neither necessary nor sufficient for growth of distal axons, whereas local
      synthesis of PC in distal axons was required for normal axonal elongation.

PMID- 7566357
TI  - The effect of kainate on protein kinase C, GABA, and the uptake of serotonin in
      the rabbit retina in vivo.
AB  - The purpose of this study was to investigate the effect of kainate on protein
      kinase C (PKC), gamma-aminobutyrate (GABA) and serotonin uptake in the rabbit
      retina. Kainate when injected into the vitreous humour produces a change in the
      GABA immunoreactivity within 6 hours. After 3 days, remnants of the normal GABA
      immunoreactivity still persist and additionally astrocyte and microglia-like
      elements "stain" positively for GABA. After 7 days exposure to kainate none of
      the normal GABA immunoreactivity is apparent, instead a number of round-shaped
      elements which may be reactive astrocytes and/or microglia stain positively for
      GABA. During these stages kainate does not affect the alpha PKC immunoreactivity
      associated with the on-bipolar cells. Six hours following kainate treatment the
      ability of certain GABA amacrine cells to take up exogenous serotonin is
      unaffected. After three days only a few of these cells can still take up
      exogenous serotonin and then not avidly. After seven days the GABA/serotonin
      amacrine cells cannot take up exogenous serotonin suggesting that all of these
      neurons are irreversibly damaged. One hour after treatment with kainate both
      calcium-dependent and -independent PKC species are translocated from the
      cytosolic to membrane compartments. After 5 hours and 7 days there was also
      evidence from the enzyme assay experiments that kainate caused the calcium
      dependent and -independent PKC enzymes to be translocated but because the total
      enzyme activity was reduced due perhaps to down-regulation of the enzyme this was
      difficult to assess precisely.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566358
TI  - Partial purification of two forms of choline kinase and separation of choline
      kinase from sphingosine kinase of rat brain.
AB  - Choline kinase of rat brain was purified approximately 200,000 fold using acid
      precipitation, ammonium sulphate fractionation, Q-Sepharose, Octyl-Sepharose and
      AH-Sepharose chromatography. The ability of this enzyme to catalyze the
      phosphorylation of choline, ethanolamine (Etn), monomethylethanolamine (MeEtn),
      dimethylethanolamine (Me2Etn) and sphingosine was investigated. Choline kinase
      was separated from sphingosine kinase. The fraction with highly purified choline
      kinase had four major polypeptides with different molecular masses and possessed
      activities towards choline, Etn, MeEtn and Me2Etn. Two forms of choline kinase
      were obtained when the enzymatically active fractions eluted from the Q-Sepharose
      column were subjected to a horizontal isoelectrofocusing electrophoresis. One
      form focused around pH 4.7 and is able to phosphorylate choline, Etn, MeEtn and
      Me2Etn. The other form focused around pH 10 and possessed only choline kinase
      activity. The latter form of choline kinase did not display classical Michaelis
      Menten's mechanism but revealed a positive co-operative pattern for two choline
      binding sites. This form was purified to apparent homogeneity with a approximate
      molecular mass of 14.4 kDa.

PMID- 7566359
TI  - Myelin basic protein purified on an ion-exchange continuous polymer bed in the
      presence of ethylene glycol and salt possesses activity against p-nitrophenyl
      acetate.
AB  - In this paper we describe a fast and mild method based on the use of a unique
      cation exchanger and buffers containing ethylene glycol and salt for the
      purification of the myelin basic protein (MBP; MW 18.5 kDa). MBP thus purified
      hydrolyses catalytically p-nitrophenyl acetate. This esterase activity
      facilitates not only the purification of MBP but also indicates that probably it
      is in its native state, i.e. there is a good chance that the purified molecules
      are structurally and chemically identical. This is a prerequisite to obtain
      crystals appropriate for x-ray diffraction and other studies.

PMID- 7566360
TI  - Methylmercury modulates GABAA receptor complex differentially in rat cortical and
      cerebellar membranes in vitro.
AB  - Effects of methylmercury (MetHg) on the specific [3H]flunitrazepam binding were
      studied in rat cortical and cerebellar P2-fractions in vitro. MetHg did not
      affect significantly the specific [3H]flunitrazepam binding in unwashed P2
      fraction but increased it marginally (by 16%) at 100 microM in washed P2
      fraction, in both brain regions. Muscimol (3 microM), a GABAA agonist, stimulated
      the [3H]flunitrazepam binding by 30% to 50% depending on the brain region. In
      washed cerebellar membranes the enhancing response of muscimol was 10 to 14%
      lower after preincubation of the tissue with MetHg but in cerebral cortex MetHg
      did not modulate the muscimol response at all. The results indicate that Met-Hg
      may have region specific effects on GABAA receptors in vitro and the effect may
      depend on the occupational state of the GABA binding domain of the receptor
      complex.

PMID- 7566362
TI  - Affinities of muscarinic drugs for [3H]N-methylscopolamine (NMS) and
      [3H]oxotremorine (OXO) binding to a mixture of M1-M4 muscarinic receptors: use of
      NMS/OXO-M ratios to group compounds into potential agonist, partial agonist, and
      antagonist classes.
AB  - The relative affinities of various muscarinic drugs in the antagonist ([3H]N
      methyl scopolamine ([3H]NMS)) and agonist ([3H]Oxotremorine-m ([3H]OXO-M))
      binding assays using a mixture of tissues containing M1-M4 receptor subtypes have
      been determined. [3H]NMS bound with high affinity (Kd = 25 +/- 5.9 pM; n = 3) and
      to a high density Bmax = 11.8 +/- 0.025 nmol/g wet weight) of muscarinic
      receptors. [3H]OXO-M appeared to bind to two binding sites with differing
      affinities (Kd1 = 2.5 +/- 0.1 nM; Kd2 = 9.0 +/- 4.9 microM; n = 4) and to a
      different population of binding sites (Bmax1 = 5.0 +/- 0.26 nmol/g wet weight;
      Bmax2 = 130 +/- 60 nmol/g wet weight). Well known antagonists exhibited high
      affinity for [3H]NMS binding but a lower affinity for [3H]OXO-M binding. The
      opposite was true for acetylcholine and other known agonists. However,
      pilocarpine and McN-A-343 had similar affinities for sites labeled by both
      radioligands. Using the ratios of antagonist-to-agonist binding affinities, it
      was possible to group compounds into apparently distinct full agonist (ratios of
      180-665; e.g. carbachol, muscarine, OXO-M, OXO-S and arecoline), partial agonist
      (ratios of 14-132; e.g. McN-A-343, pilocarpine, aceclidine, bethanechol, OXA-22
      and acetylcholine) and antagonist (ratios of 0.22-1.9; e.g. atropine, NMS,
      pirenzepine, methoctramine, 4-DAMP and p-fluorohexahydrosialo-difenidol) classes.
      These data suggest that the NMS/OXO-M affinity ratios using a mixture of M1-M4
      muscarinic receptors may be a useful way to screen and group a large number of
      compounds into apparent agonist, partial agonist, and antagonist classes of
      cholinergic agents.

PMID- 7566361
TI  - Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713
      prevents delayed neuronal death in the gerbil hippocampus.
AB  - We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl
      amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an
      acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the
      gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries
      after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham
      operated controls and the number of hypertrophic astrocytes expressing glial
      fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1
      subfield 14 days after ischemia. However, post-ischemic administration of ENA-713
      (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced
      decrease in the number of pyramidal cells by 47% of sham-operated controls,
      furthermore, it reduced the ischemia-induced accumulation of GFAP-positive
      astrocyte in the CA1 region. Together with previous results showing that ENA-713
      protected against the ischemia-induced cholinergic abnormalities in the gerbil
      brain and improved cholinergic dysfunctions in the senescent rat brain, our
      present findings suggest that ENA-713 prove to be useful for treatment with
      senile dementia such as cerebrovascular dementia.

PMID- 7566364
TI  - Properties of acetylcholinesterase reconstituted in liposomes of a different
      charge.
AB  - Acetylcholinesterase (AChE) purified from mouse brain was reconstituted in
      liposomes of a different charge, and the properties of liposome-associated AChE
      were investigated. Relative to the Km value (38.5 microM) of AChE bound to a
      neutral liposome, the value of AChE reconstituted in a negatively-charged
      liposome decreased to 23.3 microM, whereas that of AChE in a positively-charged
      liposome increased to 90.9 microM. Additionally, AChE bound to a positively
      charged liposome expressed a wider range of optimum pH than the enzyme in a
      negatively-charged liposome. In a stability study, it was found that soluble AChE
      was unstable at pH 5.5 and 7.4, while it was relatively stable at pH 10.
      Noteworthy, the immobilization of AChE to liposome enhanced the stability of
      soluble enzyme at acidic and neutral pH. Moreover, in the stabilization of the
      enzyme, a neutral liposome was more effective than charged liposomes, of which a
      positively-charged liposome was more effective than a negatively-charged liposome
      at acidic pH. Based on these results, it is proposed that while the Km value and
      the pH dependence of AChE activity are affected by the charge of liposome, the
      stability of AChE is determined mainly by a hydrophobic binding to a phospholipid
      membrane.

PMID- 7566363
TI  - Ciliary neurotrophic factor-induced gene expression in human neuroblastoma cell
      lines.
AB  - We have analyzed the response of the human neuroblastoma cell lines SK-N-SH
      (clone SY5Y) and SK-N-BE to the ciliary neurotrophic factor CNTF. In both cell
      lines CNTF induced the expression of the mRNA for two transcription factors, c
      fos and NGF1A. The induction was rapid and transient reaching a maximum between
      30 and 60 min after exposure to CNTF and subsequently declining. The level of
      induction of both c-fos and NGF1A mRNAs was much higher in SK-N-BE neuroblastoma
      cells compared to the SY5Y. Both cells express comparable levels of the
      transcript for the CNTF receptor-alpha. This mRNA was down regulated after 5 days
      of CNTF stimulation in both cell lines. CNTF also induced increased levels of the
      transcript for the growth cone associated protein GAP43 in SK-N-BE, but not in
      SY5Y cells. Induction followed a slower kinetic compared to that observed for c
      fos and NGF1A. In fact, the GAP43 mRNA levels increased during 2 days of exposure
      to CNTF. Morphological analysis of CNTF treated cells showed that SK-N-BE undergo
      significant differentiation in response to CNTF (increased number of cells with
      neurites and increased neurite length) while SY5Y did not show appreciable
      morphological differentiation. These data shows that CNTF may elicit different
      response in neuroblastoma cell lines.

PMID- 7566365
TI  - Effect of endothelin-1 induced ischemia on peroxidative damage and membrane
      properties in rat striatum synaptosomes.
AB  - Synaptosomes obtained from rat striata lesioned by central injection of
      endothelin-1 (ET-1) were analyzed for the levels of lipid peroxidation products,
      the susceptibility to lipid peroxidation, the phospholipid and free fatty acid
      composition and the activity of Na+,K(+)-ATPase one hour after ET-1 treatment.
      The intrastriatal injection of ET-1 promoted an increase of endogenous
      thiobarbituric reactive substances (TBARS), as index of free radical mediated
      lipid damage, and a greater susceptibility to iron/ascorbate-induced lipid
      peroxidation. The pattern of free fatty acids showed a significant decrease of
      arachidonic and docosahexaenoic acid consequent to ET-1 treatment. The analysis
      of lipid composition showed a significant loss of phospholipids: among
      phospholipid species, sphingomyelin and phosphatidylethanolamine plasmalogen were
      particularly reduced by ET-1 treatment. The activity of membrane-bound Na+,K(+)
      ATPase was also significantly reduced in synaptosomes obtained from ET-1 lesioned
      striata. Taken together these results indicate a significant modification of
      synaptosomal membrane of ET-1 treated rat striata, possibly due to a free radical
      mediated damage.

PMID- 7566366
TI  - Influence of Ca2+ channel modulators on [3H]purine release from rat cultured
      glial cells.
AB  - [3H]Purine release from rat striatum astrocyte cultures was studied at 14 days in
      vitro (DIV). Superfusion of cultures with a Ca(2+)-free medium + 0.5 mM ethylene
      glycol-bis(beta-aminoethylether)N,N,N',N'-tetracetic acid (EGTA) reduced the
      electrically evoked [3H]purine release. Nimodipine only at the concentration of
      10 microM modified [3H]purine outflow whereas 0.1 microM omega-conotoxin and 0.03
      0.1 microM nitrendipine reduced the evoked one. Superfusion of cultures with 0.1
      microM omega-conotoxin + 0.1 microM nitrendipine antagonized the evoked
      [3H]purine release similarly to each drug given alone. Neither nitrendipine nor
      omega-conotoxin influenced the uptake of 45Ca2+ by the cultures. The treatment of
      cells with the Ca2+ agonist Bay K 8644 did not affect [3H]purine release or the
      45Ca2+ uptake. The drug did not either alter [Ca2+]i, evaluated by loading the
      cells with 3 microM Fura-2/AM. 10-30 microM 3,4,5-trimethoxybenzoic acid 8
      (diethylamino)octyl ester (TMB-8), a blocker of intracellular Ca2+ discharge,
      significantly reduced the evoked [3H]purine release. On the other hand, 2 microM
      thapsigargin, an inhibitor of the ion store Ca2+ ATPase, was able to increase
      either the culture [3H]purine release or the [Ca2+]i. Together, the findings
      indicate that voltage-sensitive calcium channels (VSCCs) of the neuronal N and L
      types are not involved in the modulation of [3H]purine release from rat cultured
      astrocytes whereas Ca2+ coming from intracytoplasmic stores seems to play a
      prevailing role. Moreover, agents which block VSCC, seem to be able to affect
      [3H]purine outflow with mechanisms other than VSCC gating.

PMID- 7566367
TI  - Carnitine, carnitine acetyltransferase, and glutathione in Alzheimer brain.
AB  - Glutathione and "total" carnitine (i.e., free carnitine plus acid-soluble
      carnitine esters) were measured in an affected (superior frontal gyrus; SFG) and
      unaffected (cerebellum: CBL) region of Alzheimer disease (AD) and control brains.
      Average glutathione content in AD SFG (n = 13) and AD CBL (n = 7) (7.9 +/- 2.1
      and 11.9 +/- 4.0 nmol/mg protein, respectively (mean +/- S.D.)) was similar to
      that in control SFG (n = 13) and CBL (n = 6) (7.7 +/- 2.0 and 11.6 +/- 2.6
      nmol/mg protein, respectively). However, glutathione increased significantly with
      age in AD brain (p = 0.003) but not in control brain. Average total carnitine in
      AD SFG (84 +/- 47 pmol/mg protein; n = 10) and AD CBL (108 +/- 86 pmol/mg
      protein; n = 7) was not significantly different from that in the corresponding
      regions of control brain (148 +/- 97 (n = 10) and 144 +/- 107 (n = 6) pmol/mg
      protein, respectively). However, a significant decline of total carnitine with
      age in both regions was noted for AD brain, but not for control brain. Carnitine
      acetyltransferase activity in the AD SFG (n = 13) was not significantly different
      from that of control SFG (n = 13) (1.83 +/- 1.05 and 2.04 +/- 0.82 nmol/min/mg
      protein, respectively). However, carnitine acetyltransferase activity of AD CBL
      (n = 7) was significantly lower than that of control CBL (n = 6) (1.33 +/- 0.88
      versus 2.26 +/- 0.66 nmol/min/mg protein; p = 0.05).

PMID- 7566368
TI  - The tetrodotoxin-insensitive sodium current in rat dorsal root ganglia is
      unlikely to involve the expression of the tetrodotoxin-resistant sodium channel,
      SkM2.
AB  - Tetrodotoxin-insensitive (TTX-I) sodium currents have been recorded from newborn
      and adult rat sensory neurons, but the sodium channel gene(s) responsible for the
      TTX-I current are unknown. Because SkM2, one of six voltage-sensitive sodium
      channel genes cloned from rat, encodes the only cloned channel that is relatively
      resistant to tetrodotoxin, we sought to test whether the TTX-I current in rat
      sensory neurons is due to the SkM2 channel. We hypothesized that the TTX-I
      current might be generated from (1) an RNA splicing variant of SkM2, (2) post
      translational modification of the SkM2 protein, or (3) interaction with alternate
      additional channel subunits. SkM2 mRNA expression was examined in newborn rat
      dorsal root ganglia (DRG) by RNase protection assay. No SkM2 expression was
      detected. Therefore, we conclude that the TTX-I sodium current in DRG is unlikely
      to result from the expression of the SkM2 gene.

PMID- 7566369
TI  - Olfactory transduction mechanisms in sheep.
AB  - The enzyme adenylyl cyclase from sheep olfactory epithelium is dually regulated
      by GTP and is highly sensitive to the nucleotide analogues GTP gamma S and
      GppNHp, as well as to fluoride ions and forskolin. Many, but not all, odorants
      tested are able to stimulate adenylyl cyclase in a dose-dependent manner and with
      different potencies. Such an effect is detectable only in the presence of GTP.
      The odorants belonging to the putrid class are the least effective in stimulating
      adenylyl cyclase activity, and only furfuryl mercaptan significantly increases
      cAMP biosynthesis. Mixtures of two odorants, chosen among those able to activate
      adenylyl cyclase, induce additive or supra-additive effects, suggesting the
      presence of many different receptor types. The presence of an alternative
      olfactory signal transduction process, i.e. the inositol phospholipid second
      messenger system, has been evaluated. Triethylamine, a putrid odorant completely
      ineffective on cAMP levels, is able to significantly increase inositol phosphate
      accumulation, indicating the coexistence of both cAMP- and InsP3-mediated
      signalling pathways in sheep olfactory epithelium.

PMID- 7566370
TI  - Methylfolate modulates potassium evoked neuro-secretion: evidence for a role at
      the pteridine cofactor level of tyrosine 3-hydroxylase.
AB  - We have previously shown that 5-methyltetrahydrofolate influences neuro
      secretion. The present study more precisely characterises the processes involved
      and considers one probable site of action. Focusing on the tyrosine-noradrenalin
      axis in cerebellum we showed 5-methyltetrahydrofolate causes a significant
      reduction in the apparent K+ evoked secretion of noradrenalin to only 12.9% of
      control release. Evidence supports the idea that this could actually be due to
      increased synthesis leading to; depletion of reserves, possibly through leakage,
      exocytotic inhibition via activation of presynaptic receptors or end product
      inhibition by noradrenalin at the pteridine cofactor level of tyrosine
      hydroxylase: a) concomitant decreased measurement of perfusate and intracellular
      tyrosine with released noradrenalin following 5-methyltetrahydrofolate treatment
      supports the idea of increased transmitter turn over; b) kinetic studies indicate
      that at saturating concentrations of tyrosine and in the presence of an inhibitor
      of L-DOPA decarboxylase, 5-methyltetrahydrofolate partially duplicates the rate
      limiting behaviour of a synthetic pteridine cofactor--DL,2-amino-4-hydroxy
      6,7,dimethyltetrahydropteridine. We debate whether, in vivo, CSF 5
      methyltetrahydrofolate might interact at the tetrahydrobiopterin cofactor level
      of tyrosine hydroxylase and other aromatic amino-acid hydroxylases.

PMID- 7566371
TI  - A possible mechanism for the hypoxia-hypoglycemia-induced release of excitatory
      amino acids from cultured hippocampal astrocytes.
AB  - In order to elucidate the mechanism of release of excitatory amino acid (EAA)
      induced by hypoxia-hypoglycemia (in vitro ischemia) from cultured hippocampal
      astrocytes, we compared the EAA release by in vitro ischemia with those by other
      treatments. The EAA release induced by in vitro ischemia treatment was rapid and
      reversible. The amount of released aspartate was comparable to that of glutamate,
      although the endogenous content of aspartate was one sixth that of glutamate.
      High-K (100 mM) treatment and the addition of 5 mM NaCN induced a rapid EAA
      release and the glutamate release was much greater than aspartate. Addition of 5
      mM iodoacetate, a glycolysis inhibitor, induced a slow EAA release, and the
      amount of released aspartate was much higher than that of glutamate. On the other
      hand, the in vitro ischemia treatment and the addition of 5 mM NaCN induced only
      20% reduction in ATP content for initial 5 min, whereas the addition of 5 mM
      iodoacetate induced a marked reduction. Our data suggest that ischemia-induced
      EAA release from astrocytes is a complex process in which local energy failure,
      inhibition of glycolysis, and depolarization of the cell membrane are involved.

PMID- 7566373
TI  - Effects of local and repeated systemic administration of (-)nicotine on
      extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in
      rat cortex.
AB  - Systemically administered (-)nicotine (0.2-1.2 mg/kg, s.c.) significantly
      increased the release of acetylcholine (ACh), norepinephrine (NE) and dopamine
      (DA) in rat cortex. The lowest dose of (-)nicotine examined (0.2 mg/kg, s.c.)
      also significantly elevated extracellular serotonin (5-HT) levels, and the
      maximal increases of extracellular ACh (122% at 90 min post injection) and DA
      levels (249% at 120 min post-injection) were observed following this dose. In
      contrast, the maximal increase of NE release (157% at 30 min post-injection) was
      observed following the highest dose of (-)nicotine injected (1.2 mg/kg, s.c.).
      This higher dose consistently produced generalized seizures. Repeating the (
      )nicotine (0.58 mg/kg, s.c.) injection four hours after the first administration
      significantly elevated extracellular NE levels and also appeared to increase DA
      and ACh release. In addition, extracellular ACh and DA levels increased
      significantly in the dialysate after (-)nicotine was administered directly to the
      neocortex through the microdialysis probe membrane. Norepinephrine levels
      appeared to be elevated in the cortex following local administration as well.

PMID- 7566372
TI  - Increased locus coeruleus glutamate levels are associated with naloxone
      precipitated withdrawal from butorphanol in the rat.
AB  - Extracellular fluid levels of glutamate were measured in the locus coeruleus
      during butorphanol (a mixed agonist at mu-, delta-, and kappa-opioid receptors)
      withdrawal by using microdialysis in conscious butorphanol-dependent Sprague
      Dawley rats. Guide cannulae were implanted chronically and rats were given
      intracerebroventricular (i.c.v.) infusions of butorphanol (26 nmol/1
      microliter/hr) or saline (1 microliter/hr) for 3 days. Microdialysis probes (2 mm
      tip) were inserted into the locus coeruleus 24 hr before precipitation of
      withdrawal by i.c.v. injection of naloxone (48 nmol/5 microliters). A separate
      series of rats was rendered dependent by peripheral injection of butorphanol (20
      mg/kg, s.c., b.i.d.) for 5 days and naloxone (5 mg/kg, i.p.) was given to
      precipitate withdrawal. Single injections of butorphanol (26 nmol/5 microliters,
      i.c.v.) had no effect on the extracellular fluid levels of glutamate, compared to
      rats injected with vehicle. Behavioral evidence of withdrawal was detected
      following naloxone challenge in butorphanol-dependent rats (both i.c.v. and s.c.
      models), but not in non-dependent, vehicle-treated rats. Significant increases (P
      < 0.05) in levels of glutamate were noted after naloxone-precipitated withdrawal
      only in the butorphanol group. The glutamate levels in the locus coeruleus
      increased from 8.37 +/- 2.01 before, to 21.93 +/- 4.58 microM in the first 15 min
      sample following i.c.v. injections of 48 nmol/5 microliters naloxone and from
      10.84 +/- 1.74 before, to 26.01 +/- 6.19 microM in the 15-30 min sample following
      i.p. injections of 5 mg/kg naloxone in the butorphanol-dependent rats,
      respectively. These results provide direct evidence to support the role of
      excitatory amino acids within the locus coeruleus in butorphanol withdrawal.

PMID- 7566375
TI  - Attempted induction of blood brain barrier in vitro by co-culture of gerbil brain
      microvessel endothelial cells and glial cells.
AB  - The characteristics of isolated and subcultured Mongolian gerbil brain
      microvessel endothelial cells (BECs) were investigated, especially the
      disappearance of blood brain barrier (BBB) functions, and subcultured BECs were
      co-cultured with gerbil glial cells to assess a mass-producible BBB filter model.
      The subcultured cells lost specific characteristics observed in freshly isolated
      BECs, such as limited permeability to albumin and inulin, high gamma-glutamyl
      transpeptidase activity, and strong connections between individual cells. The
      subcultured BECs did not regain BBB functions during co-culture with glial cells,
      even derived from the same species. Only freshly isolated endothelial cells can
      be used for the BBB filter model, and a mass-producible BBB filter model may be
      impossible to make.

PMID- 7566374
TI  - Analysis of glutamate receptors in primary cultured neurons from fetal rat
      forebrain.
AB  - In order to further analyze the development of glutamatergic pathways in neuronal
      cells, the expression of excitatory amino acid receptors was studied in a model
      of neurons in primary culture by measuring the specific binding of L
      [3H]glutamate under various incubation conditions in 8-day-old intact living
      neurons isolated from the embryonic rat forebrain, as well as in membrane
      preparations from these cultures and from newborn rat forebrain. In addition, the
      receptor responsiveness to glutamate was assessed by studying the uptake of
      tetraphenylphosphonium (TPP+) which reflects membrane polarization. In the
      presence of a potent inhibitor of glutamate uptake, the radioligand bound to a
      total number of sites of 36.7 pmol/mg protein in intact cells incubated in a Tris
      buffer containing Na+, Ca2+, and Cl-, with a Kd around 2 microM. In the absence
      of the above ions, [3H]glutamate specific binding diminished to 14.2 pmol/mg
      protein with a Kd-value of 550 nM. Under both of the above conditions, similar Kd
      were obtained in membranes isolated from cultures and from the newborn brain.
      However, Bmax-values were significantly lower in culture membranes than in intact
      cells or newborn membranes. Displacement studies showed that NMDA was the most
      potent compound to inhibit [3H]glutamate binding in membranes obtained from
      cultured neurons as well as from the newborn brain, whereas quisqualate, AMPA,
      kainate and trans-ACPD were equally effective.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566376
TI  - Brainstem auditory evoked potentials recorded around the human upper brainstem
      area.
AB  - The intracranial spatiotemporal distributions of brainstem auditory evoked
      potentials were analyzed in two patients with epilepsy to study the dipole
      directions of waves III and V, previously found to have a horizontal and a
      vertical dipole, respectively. Depth electrodes were implanted bilaterally into
      the frontal and temporal lobes of these patients, the targets including the
      amygdala and hippocampus which are close to the upper pons and midbrain.
      Recordings around the upper pons and from the subcortical area downwards along
      the dorsal aspect of the upper pons indicated that waves III and V are
      constructed of mixed dipoles, wave III also having a vertical dipole segment and
      wave V also a horizontal one. These results suggest that several neural
      activities from the upper pons to midbrain contribute to the generation of waves
      III and V.

PMID- 7566377
TI  - Recurrent primary central nervous system lymphoma mimicking neurodegenerative
      disease--an autopsy case report.
AB  - A 42-year-old female presented with recurrent primary central nervous system
      lymphoma mimicking the roentgenographic appearance of diffuse brain degeneration.
      Betamethazone was administered, but her condition worsened. Biopsy of a swollen
      neck lymph node demonstrated lymphoma cells. Computed tomography and magnetic
      resonance (MR) imaging showed no contrast-enhanced lesions. T2-weighted MR
      imaging revealed diffuse, high intensity areas in the white matter of the
      bilateral cerebrum, basal ganglia, and brainstem. Despite chemotherapy for
      systemic lymphoma, she died of respiratory arrest. Histological examination of
      autopsy specimens showed diffuse infiltration of lymphoma cells in the
      perivascular space of the cerebral cortex, but little neovascularization. The
      absence of contrast enhancement may have been due to preservation of the blood
      brain barrier. Histological confirmation of roentgenographic findings of brain
      degeneration is important in patients treated for primary central nervous system
      lymphoma.

PMID- 7566378
TI  - Primary intracranial epithelioid angiosarcoma--case report.
AB  - A 39-year-old male presented with an exceedingly rare primary intracranial
      epithelioid angiosarcoma in the right parietal lobe manifesting as weakness of
      the left hand. Neuroimaging revealed a well-defined intensely enhanced lesion in
      the right parietal lobe with peripheral cerebral edema. The tumor was grossly
      totally removed. Light microscopy of the surgical specimens revealed features
      typical of an epithelioid vascular tumor. The tumor cells showed intense positive
      immunohistochemical staining for cytokeratin and vimentin and focally positive
      staining for both Ulex europaeus agglutinin and anti-human endothelial cells,
      CD31. Tumor regrowth required two further operations. This progressive growth was
      consistent with an angiosarcoma. The tumor was diagnosed as an epithelioid
      angiosarcoma based on the histological and clinical characteristics. He became
      progressively obtunded and finally died. This is the first intracranial
      epithelioid angiosarcoma which expressed epithelial markers detectable by
      immunohistochemical methods.

PMID- 7566379
TI  - Acute revascularization for bihemispheric anterior cerebral artery thrombosis-
      case report.
AB  - A 65-year-old male presented with rapidly progressive paraparesis and akinetic
      mutism due to occlusion of the bihemispheric anterior cerebral artery (ACA). He
      was treated by intra-arterial thrombolytic therapy but reocclusion of the
      arteriosclerotic lesion occurred. Bilateral superficial temporal artery (STA)-ACA
      anastomoses achieved lasting neurological improvement. Bilateral STA-ACA
      anastomoses are quite effective to prevent ischemia of the bilateral ACA
      territories.

PMID- 7566380
TI  - Spontaneous dissection in the common carotid artery--case report.
AB  - A 60-year-old female presented with a very rare spontaneous dissection in the
      common carotid artery manifesting as disturbance of consciousness and left dense
      hemiparesis immediately after swimming. Cerebral angiography showed complete
      obstruction of the right common carotid artery. Endarterectomy was performed to
      remove the subintimal thrombus and dissected intima. Blood flow was re
      established 4 hours after onset of symptoms. Her disturbance of consciousness was
      resolved and left dense hemiparesis disappeared completely 12 hours after onset.

PMID- 7566381
TI  - Arteriovenous malformation associated with a large cyst--case report.
AB  - A 37-year-old male presented with an arteriovenous malformation in the left
      temporal lobe associated with a large cyst. The cyst was drained and the nidus
      completely excised. The histological findings suggest that repeated subclinical
      hemorrhages from neovascular channels of the cyst membrane was responsible for
      the growth of the cyst.

PMID- 7566382
TI  - Hemifacial spasm in Albright's hereditary osteodystrophy with
      pseudopseudohypoparathyroidism and nephrogenic diabetes insipidus--case report.
AB  - A 30-year-old male with Albright's hereditary osteodystrophy,
      pseudopseudohypoparathyroidism, and nephrogenic diabetes insipidus presented with
      hemifacial spasm persisting for 2 years. This association is extremely unusual.
      Angiography revealed markedly tortuous carotid and vertebral arteries
      inconsistent with his age. Neurovascular decompression of the left vertebral
      artery achieved only partial resolution of the spasm.

PMID- 7566384
TI  - Cervical flexion myelopathy associated with cervical spina bifida occulta--case
      report.
AB  - A 16-year-old boy presented with segmental muscular atrophy of the bilateral
      distal upper extremities. Cervical spine x-ray films showed occult spina bifida
      from C-1 to T-1 associated with an abnormal long club-like bone located parallel
      to the epidural space between C-5 and C-7. In neck flexion, the cervical spinal
      cord was stretched and compressed to the posterior aspect of the vertebral body.
      Moreover, the dorsally placed abnormal bone migrated ventrally, indenting the
      dorsal portion of the spinal cord. This is quite an unusual case of so-called
      "flexion myelopathy," aggravated by the abnormal bone located dorsally.

PMID- 7566383
TI  - Associated injuries and mechanism of atlanto-occipital dislocation caused by
      trauma.
AB  - Injuries associated with traumatic atlanto-occipital dislocation (AOD) leading to
      death were analyzed in 11 patients, nine injured by traffic accidents, of which
      five were victims of car-pedestrian accidents. On admission, unconsciousness and
      respiratory arrest were noted in all patients, and cardiac arrest in nine. Skull
      and cervical roentgenograms revealed enlargement of the retropharyngeal space due
      to injury of the vertebral artery or its branches in nine patients, atlanto-axial
      dislocation (C-1-C-2 separation) in four, and skull fracture in four. Computed
      tomography demonstrated subarachnoid hemorrhage (SAH) in the upper cervical and
      posterior fossa in nine patients, fourth ventricular hematoma in seven, and atlas
      fracture in three. SAH and ventricular hematoma were due to craniocervical
      injury. Other common injuries were injury of face and head excluding the
      mandibular region in 10 patients, mandibular fracture in three, severe chest
      injuries in eight, and intraperitoneal bleeding in two. The overall outcome was
      poor. Nine patients died within 13 hours of admission, one was diagnosed as brain
      dead 8 days after the accident, and the other one survived in a persistent
      vegetative state. Early death is probably caused by associated severe injuries,
      i.e. chest injuries and intraperitoneal bleeding rather than AOD. Although injury
      of the mandibular region is known to be associated with AOD, head, breast, and
      abdominal trauma may also lead to neck hyperextension-flexion in various
      directions. Whatever the direct cause, a distractive force to the craniocervical
      joint by hyperextension-flexion appears to be important in the mechanism of AOD.

PMID- 7566385
TI  - Neutral red staining for the assessment of acute outcome in rat focal cerebral
      ischemia models.
AB  - Neutral red staining was evaluated as an acute outcome assessment method in rat
      models of cerebral ischemia by comparison with histological infarction volume.
      Fischer 344 rats (n = 48) were used in three different models of middle cerebral
      artery (MCA) occlusion: proximal MCA occlusion (n = 16), distal MCA occlusion
      followed by ipsilateral common carotid artery (CCA) occlusion (distal MCA/CCA
      occlusion, n = 15), and MCA occlusion with an intravascularly introduced 4-0
      nylon suture (intravascular MCA occlusion, n = 17). At 1 hour, 2 hours, and 4
      hours after MCA occlusion, animals were injected with 2.5 ml of 4% neutral red
      solution via the femoral vein, and then sacrificed. Proximal MCA occlusion caused
      a neutral red defect volume in the cortex which correlated well with histological
      infarction volume at 4 hours (r = 0.88, p < 0.05), and in the caudate which
      correlated well with infarction volume at 4 hours (r = 0.94, p < 0.01). Distal
      MCA/CCA occlusion caused a neutral red defect volume in the cortex lager than the
      histological infarction volume (4 hrs: 88.6 +/- 11.8 vs. 74.3 +/- 17.4 mm3, p <
      0.05) but closely correlated with the infarction volume at 4 hours (r = 0.81, p <
      0.05). Intravascular MCA occlusion caused a neutral red defect volume in only two
      of 17 animals after 1-4 hours, which correlated well with the absence of
      histological evidence of infarction. Neutral red staining is a simple method for
      assessing the acute outcome of focal cerebral ischemia as early as 4 hours after
      the onset, in an appropriate model of cerebral ischemia.

PMID- 7566387
TI  - Intracerebral infiltration by monoclonal plasmacytoid cells in Waldenstrom's
      macroglobulinemia--case report.
AB  - A 68-year-old female presented with Waldenstrom's macroglobulinemia with
      infiltration into the cerebral parenchyma manifesting as increased confusion,
      memory loss, and disorientation. She had a past history of Waldenstrom's
      macroglobulinemia treated 3 years before. Magnetic resonance imaging showed a
      high intensity area on T2-weighted images in the left frontal lobe extending to
      the corpus callosum which was well enhanced by gadolinium-diethylenetriaminepenta
      acetic acid. Direct infiltration of neoplastic cells was confirmed by biopsy.
      Immunohistochemical examination showed that mature plasmacytoid cells in the
      cerebral parenchyma were immunoglobulin M and lambda light chain antigen
      positive, but immature lymphocytes in Virchow-Robin space were negative.
      Monoclonal proliferation was confirmed by southern blot analysis. She became
      symptom free and the size of the lesion was dramatically reduced after 40 Gy
      irradiation. She showed no evidence of recurrence 3 years after irradiation. As
      no effective chemotherapy regimen for Bing-Neel syndrome has been established,
      irradiation is worth considering when neuroimaging suggests intracranial
      infiltration of neoplastic cells.

PMID- 7566386
TI  - p55 and p75 tumor necrosis factor receptor expression on human glioblastoma
      cells.
AB  - Expression of the two types of tumor necrosis factor (TNF) receptor, p55 and p75,
      in 12 human glioblastoma cell lines was studied. Reverse-transcription polymerase
      chain reaction detected messenger ribonucleic acid (mRNA) transcripts of p55 TNF
      receptor in all 12 cell lines tested, but p75 TNF receptor mRNA in only four cell
      lines. Flow cytometric analysis with anti-p55 and anti-p75 TNF receptor
      monoclonal antibodies demonstrated both p55 and p75 proteins in these four cell
      lines, but the level of expression of p75 molecule was very low. Correlation of
      p55 and p75 TNF receptor expression with TNF-induced growth suppression and
      production of bioactive molecules (interleukin-6, interleukin-8, manganase
      superoxide dismutase, prostaglandin E2) showed that p55 TNF receptor mediates
      these TNF actions, but none of the responses were influenced by the presence of
      the p75 TNF receptor, which apparently has no specific role.

PMID- 7566388
TI  - Magnetic resonance angiography of cerebral arteriovenous malformations.
AB  - Magnetic resonance (MR) angiography as a method for the long-term follow-up of
      cerebral arteriovenous malformations (AVMs) was assessed in 14 patients with
      cerebral AVMs. These patients were either untreated or treated with transarterial
      embolization and/or stereotactic radiosurgery (gamma knife). Two-dimensional- and
      three-dimensional (3D)-time-of-flight (TOF) techniques were useful for following
      AVMs with a small nidus and few feeders and drainers which were either untreated
      or had been treated only a few months previously. 3D-TOF MR angiography with a
      contrast agent was more useful for visualizing the vascular structure, including
      the residual nidus, during long-term follow-up of treated AVMs.

PMID- 7566389
TI  - Simultaneous bilateral hypertensive intracerebral hemorrhages--two case reports.
AB  - A 65-year-old male and an 80-year-old female presented with unusual simultaneous
      bilateral hypertensive intracerebral hemorrhages in the putamina and thalami,
      respectively. The hematomas were demonstrated by computed tomography performed
      within a few hours of onset. The patients underwent conservative therapy. The
      male patient died 4 days after the onset and the female finally became
      vegetative. The majority of patients with bilateral intracerebral hemorrhages
      generally have a poor outcome due to the development of severe disturbed
      consciousness, tetraparesis, and pseudobulbar palsy, even if the hematomas are
      not so large. The indication of surgery for this type of hemorrhage may be
      confined to patients with small hematomas who can be expected to have a good
      functional outcome after removal of the larger hematoma.

PMID- 7566390
TI  - Aneurysm of the distal anterior inferior cerebellar artery--case report.
AB  - A 38-year-old female presented with vertigo, right hearing disturbance, and
      slight headache which were treated medically. However, she suddenly developed
      severe headache with vomiting and vertigo. Computed tomography revealed
      subarachnoid hemorrhage, and right vertebral angiography disclosed a rare
      aneurysm at the distal portion of the anterior inferior cerebellar artery. She
      underwent a right suboccipital craniectomy in the lateral position. The aneurysm
      could not be clipped because the aneurysm was tightly adhered to the brainstem,
      so it was trapped. Postoperatively, she showed slight VIIIth to Xth cranial nerve
      disturbances. Three months postoperatively, the IXth and Xth cranial nerve
      disturbances had disappeared, but the tinnitus and right hearing disturbance were
      still present. The initial symptoms were probably caused by minor bleeding from
      the aneurysm.

PMID- 7566391
TI  - Simultaneous occurrence of aneurysmal subarachnoid hemorrhage and remote
      intracerebral hemorrhage--case report.
AB  - A 77-year-old female presented with a rare aneurysmal subarachnoid hemorrhage
      accompanied by a remote hypertensive intracerebral hemorrhage. With a past
      history of hypertension, she suddenly developed right hemiparesis followed by
      delayed loss of consciousness. Left carotid angiography demonstrated a left
      internal carotid-posterior communicating artery aneurysm. The intracerebral
      hematoma was located in the posterior limb of the internal capsule ipsilateral to
      the ruptured aneurysm. The aneurysm was clipped with a fenestrated clip 3 weeks
      after the onset. The rise in blood pressure at the onset of intracerebral
      hemorrhage probably caused the rupture of the internal carotid-posterior
      communicating artery aneurysm.

PMID- 7566392
TI  - Surgical removal of pineal region meningioma--three case reports.
AB  - Three patients with large or huge meningiomas of the pineal region presented with
      headache, vomiting, gait and visual disturbance, apraxia, agnosia, and transient
      amnestic aphasia. Computed tomographic scans revealed round, high-density areas
      of 8 x 7 x 7 cm, 5 x 5 x 4 cm, and 3 x 3 x 3 cm in the pineal region. Angiography
      revealed that the bilateral internal cerebral veins and the great vein of Galen
      were stretched and significantly displaced upward in one patient, and downwards
      in the other two. The meningiomas appeared to originate from the verum
      interpositum and falcotentorial junction, respectively. The tumors were removed
      subtotally or totally via an occipital interhemispheric transtentorial approach
      and/or infratentorial supracerebellar approach. The postoperative courses were
      uneventful, and no neurological deficit was detected postoperatively. Pineal
      region tumors with a maximum diameter of 5 cm or larger should be operated on via
      a unilateral or bilateral occipital interhemispheric transtentorial approach,
      regardless of the angiographic findings, because this permits a wide operative
      field and can be followed, if necessary, by an infratentorial supracerebellar
      approach. Selection of the operative approach for a relatively small pineal
      region tumor should depend on the angiographic findings: downward displacement of
      the bilateral internal cerebral veins and the great vein of Galen indicates an
      occipital interhemispheric transtentorial approach, whereas upward displacement
      indicates an infratentorial supracerebellar approach.

PMID- 7566393
TI  - Intra-arterial ACNU and cisplatin chemotherapy for the treatment of glioblastoma
      multiforme.
AB  - Intra-arterial (IA) chemotherapy has achieved no obvious clinical superiority as
      a treatment for glioblastoma multiforme despite the many theoretical advantages.
      The clinical courses of 38 patients who underwent surgery and radiotherapy with
      IA 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea
      hydrochloride (ACNU) and cisplatin were reviewed. Tumor regrowth was evaluated by
      comparison of contrast-enhanced areas on computed tomographic scans. The initial
      response rate was 19 of 32 patients evaluated, and the median survival time (MST)
      for all 38 patients was 53 weeks. Local recurrence was observed in 20 patients,
      and distant recurrence (areas more than 3 cm from the original tumor margin) was
      observed in 15 patients. The MST was 59 weeks for patients without distant
      recurrence, and 42 weeks for patients with distant recurrence (statistically not
      significant). Adjuvant IA ACNU and cisplatin chemotherapy did not improve the
      survival time. An important clinical feature was the high incidence of distant
      recurrence, in contrast to experience with other conventional therapy regimens.
      Distant recurrence, without extended survival, may suggest insufficient control
      of tumor regrowth.

PMID- 7566394
TI  - Linear transverse forehead incision for patients with alopecia praematura-
      technical note.
AB  - A method for craniotomy via a transverse linear scalp incision on the forehead
      wrinkle line with cosmetic reconstruction is described. The method requires
      minimal knowledge of plastic surgical techniques. Operative scars are
      inconspicuous and the normal appearance of the forehead can be retained, which is
      especially valuable for patients with alopecia praematura.

PMID- 7566395
TI  - Effects of trapidil and suramin on growth factor-induced calcium response and
      tyrosine phosphorylation in human glioma cells.
AB  - Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce
      the proliferation of glioma cells in vitro. Trapidil and suramin inhibit this
      growth factor-stimulated glioma cell growth, but the mechanisms are not fully
      understood. The effects of trapidil and suramin on PDGF- and EGF-induced early
      biochemical events in T98G cells were studied. PDGF induced a rapid increase of
      intracellular free calcium concentration ([Ca2+]i) in fura-2/acetoxymethyl ester
      loaded single glioma (T98G) cells. This increase was completely inhibited by
      removal of extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)
      N,N,N,N-tetraacetic acid but not by an L-type calcium channel blocker
      (nicardipine), suggesting that PDGF may cause calcium influx through voltage
      independent calcium channels in T98G cells. Trapidil and suramin blocked the PDGF
      induced calcium response and inhibited the PDGF-initiated tyrosine
      phosphorylation of the PDGF receptor as detected by Western blot analysis using
      an antibody specific for phosphotyrosine. Trapidil and suramin also inhibited EGF
      initiated calcium response in T98G cells, but only partially inhibited EGF
      initiated tyrosine phosphorylation at the same concentrations. Our results
      suggest that trapidil and suramin inhibit PDGF- and EGF-initiated early
      biochemical events, and thus suppress growth factor-induced cell proliferation.

PMID- 7566396
TI  - 192Ir induced radiation damage in monkey brain assessed with magnetic resonance
      imaging and histological examination.
AB  - The effects of irradiation on a large volume of normal brain tissue as occurs in
      interstitial brachytherapy were investigated. Double iridium-192 seed assemblies
      were stereotactically implanted into the right centrum semiovale of eight adult
      Japanese monkeys (Macaca fuscata). The morphological changes induced in the
      normal brain tissue were evaluated with magnetic resonance (MR) imaging with and
      without gadolinium-diethylenetriaminepenta-acetic acid (Gd) enhancement at 2 days
      and 1, 3, and 6 months after the brachytherapy. After each MR imaging
      examination, randomly selected experimental animals were sacrificed to analyze
      the histological changes. The low intensity area seen inside the ring of contrast
      enhancement on the T1-weighted image with Gd enhancement was well correlated with
      histologically defined necrosis. The high intensity area seen outside the area
      showing contrast enhancement on the T2-weighted image was well correlated with an
      area of histological edema and demyelination. The sizes of the lesion and the
      high intensity area were maximum during the acute stage (2 days) following
      interstitial irradiation. This monkey model with MR imaging can be used to
      investigate the development of brain damage induced by interstitial irradiation.
      We further recommend careful monitoring to detect the development of brain edema
      during the acute stage after interstitial brachytherapy, especially when large
      tumors are treated.

PMID- 7566397
TI  - Clinical application of diffusion-weighted magnetic resonance imaging to
      intracranial disorders.
AB  - Diffusion-weighted magnetic resonance imaging was performed to determine the
      changes in water diffusion and to investigate the detectability of diffusion
      anisotropy in patients with intracranial disorders. Diffusion maps of the
      apparent diffusion coefficient (ADC) were created of 19 patients with cerebral
      infarction, five with intracerebral hematoma, four with glioma, four with
      meningioma, four with hydrocephalus, and five with subdural hematoma. ADC was
      increased in chronic cerebral infarction and glioma, and decreased in acute
      cerebral infarction, meningioma, and the marginal area of glioma compared with
      the ADC of the normal gray matter. There was a significant difference in ADC
      between the marginal and internal areas of glioma. Increased ADC may be due to
      increased vasogenic edema in infarction and a lack of significant restriction of
      diffusion within glioma. Decreased ADC can be attributed to restricted diffusion
      caused by cytotoxic edema in infarction and the underlying histological pattern
      of densely packed tumor cells in glioma. Diffusion anisotropy of the internal
      capsule was less detectable in pathological than normal hemispheres. Diffusion
      anisotropy was less detectable in patients with hydrocephalus and subdural
      hematoma. Intracranial lesions were thought to have influenced the compression of
      the brain structures and cells, resulting in decreased diffusion. The measurement
      of ADC by diffusion-weighted magnetic resonance imaging has the potential for
      greater understanding of the biophysical changes in various intracranial
      disorders, including correct diagnosis of cerebral infraction, and histological
      diagnosis of brain tumor.

PMID- 7566398
TI  - Primary malignant lymphoma of the central nervous system--report of four long
      term survivors.
AB  - Four of 47 patients treated between 1977 and 1993 for histologically confirmed
      primary malignant lymphoma of the central nervous system (non-Hodgkin's type of B
      cell origin) achieved long-term survival for more than 5 years with a good
      quality of life. Three have remained disease-free for 9-12.5 years. The fourth
      achieved complete remission for more than 5 years before death from tumor
      recurrence. All four patients were treated with a standard therapeutic regimen,
      consisting of radiotherapy (50-60 Gy local and 30-40 Gy whole brain irradiation)
      followed by four to six courses of chemotherapy with cyclophosphamide,
      vincristine, adriamycin, and prednisolone at 4- to 8-week intervals. No further
      treatment was performed after remission had been obtained. No specific predictors
      for long-term survival including sex, age, tumor location, multiplicity of
      lesions, histology, or treatment modality was identified. All four patients
      showed an immediate tumor response to radiation. We recommend chemotherapy at
      increasing intervals as part of the post-therapeutic management of long-term,
      disease-free patients.

PMID- 7566399
TI  - Clinical features of progressive lacunar infarction--retrospective analysis of
      patients with motor syndromes.
AB  - The clinical features of progressive lacunar infarction were analyzed in 20
      patients with lacunar infarction. Seven of the 20 patients experienced paresis
      progression and the remaining 13 patients had a stable course. The mean age of
      progressive lacunar infarction patients (78.6 +/- 4.30 yrs) was significantly
      higher than that of stable lacunar infarction patients (65.1 +/- 7.68 yrs) (p <
      0.01). Patients presenting with pure motor stroke were more likely to have
      progressive stroke (7/13) than those presenting with sensorimotor stroke (0/7) (p
      < 0.05). Paresis aggravation began on Day 1 and ceased on Day 2 in most patients.
      Progressive paresis began to improve after reaching the nadir. Hemiparesis was
      only slightly worse after 1 month compared with that on admission. Older patients
      are more likely to have a progressive course. Paresis progression in lacunar
      patients does not preclude the possibility of recovery and is not necessarily
      associated with a poor prognosis.

PMID- 7566400
TI  - Unusual location of intracranial vagus neurinoma--case report.
AB  - A 55-year-old male presented with hearing disturbance and tinnitus in the left
      ear. Computed tomography (CT) and magnetic resonance imaging demonstrated a well
      defined, homogeneously enhanced mass in the left cerebellomedullary cistern
      without extension close to the jugular foramen. A three-dimensional image
      reconstructed from thin-slice CT scans demonstrated that the mass was clearly
      separated from the jugular foramen. The mass lesion was totally removed
      surgically. At surgery the tumor was found to originate from one rootlet of the
      vagal nerve just after its exit from the medulla oblongata. The histological
      diagnosis was neurinoma. Intracranial neurinomas of the glossopharyngeal, vagal,
      or accessory nerve usually originate within or close to the jugular foramen. This
      unusual location made it difficult to achieve a correct preoperative diagnosis.

PMID- 7566401
TI  - Ruptured aneurysm at the origin of duplication of the middle cerebral artery-
      case report.
AB  - A 28-year-old male presented with a rare case of an aneurysm at the origin of
      duplication of the middle cerebral artery manifesting as subarachnoid hemorrhage.
      Preoperative angiography revealed duplication of the right middle cerebral artery
      and an aneurysm at its origin, which was successfully clipped. He was discharged
      with no neurological deficits. Congenital factors may be more important in the
      etiology of aneurysms associated with this anomaly.

PMID- 7566402
TI  - Acute thrombolytic therapy and subsequent angioplasty for atherosclerotic
      stenosis of the basilar artery--case report.
AB  - A 50-year-old male presented with severe atherosclerotic stenosis of the basilar
      artery at its origin with very poor blood flow distally, manifesting as sudden
      onset of deterioration of consciousness to semicomatose with decerebrate posture.
      He regained consciousness dramatically after acute thrombolysis, although right
      hemiparesis persisted due to left pontine infarction. Follow-up angiography after
      3 months of antiplatelet and anticoagulation therapy demonstrated severe residual
      stenosis of the basilar artery. Percutaneous transluminal angioplasty (PTA)
      resulted in wide patency of the basilar artery stenosis with excellent blood flow
      distally. Combination of acute thrombolytic therapy and subsequent PTA is an
      effective treatment for severe basilar artery occlusive disease.

PMID- 7566403
TI  - Thoracic intradural anterior epidermoid manifesting as sudden onset of paraplegia
      -case report.
AB  - A 32-year-old female presented with a rare thoracic intradural anterior
      epidermoid tumor manifesting as acute onset of paraplegia. The tumor was
      completely removed through a laminectomy. She achieved a full neurological
      recovery. This is a very unusual presentation for an epidermoid tumor.

PMID- 7566404
TI  - Juvenile parkinsonism treated with bilateral pallidotomies--case report.
AB  - A 47-year-old female diagnosed as having juvenile parkinsonism at age 38 years
      developed progressive motor fluctuation while receiving levodopa medication. She
      underwent right posteroventral pallidotomy which achieved only a transient effect
      on the wearing-off. An additional procedure on the left pallidum resulted in long
      lasting relief of the parkinsonian symptoms.

PMID- 7566405
TI  - [The use of gammaglobulin for preventing infection in stroke].
AB  - In the study the influence of giving gammaglobulin on the course of stroke was
      tested. The trial was double blind, with a control group and with a randomised
      administering of gammaglobulin and placebo. The condition for including a patient
      in the trial was clinical diagnosis of stroke, period of time from the onset not
      longer than five days, and the absence of both clinical and laboratory features
      of infection. 36 patients were given gammaglobulin (Veinoglobulin Institut
      Merieux) in 10 g doses at 3-day intervals, 35 patients were given placebo: 10g of
      albumin. The clinical follow-up lasted 30 days. Three patients from the
      gammaglobulin group and nine patients from the placebo group died. Administration
      of gammaglobulin decreased the tisc of death by 74%. The improvement of
      neurological deficit in 30-day survivals in the treated group was more expressed
      than in the placebo group. The total number of infections, number of days with
      increased temperature, number and time of given antibiotics were comparable in
      both groups. The results obtained suggest that prophylactic treatment with
      gammaglobulin does not prevent infections but their course is milder with
      consequent better clinical improvement and lower mortality.

PMID- 7566406
TI  - [The thyroid function markers and their prognostic significance patients with
      ischemic stroke].
AB  - Thyroid hormones serum concentration alters in a variety of nonthyroidal
      illnesses. Thyroxine and triiodothyronine levels in patients after ischaemic
      stroke are significantly lower and reverse-triiodothyronine (rT3) and
      triiodothyronine uptake index (T3I) are considerably higher. At the beginning of
      insultus rT3 and T3I can be used as the markers of fatal prognosis.

PMID- 7566407
TI  - [Cerebrolysin in treatment of acute ischemic stroke].
AB  - Cerebrolysin is composed of low molecular peptides and free amino-acids and as a
      nootropic drug it administered in various diseases of central nervous system. In
      an open clinical trial patients with acute ischaemic stroke in the region of the
      middle cerebral artery, were treated. Cerebrolysin was administered as
      intravenous infusion in daily dose of 15 ml during 21 days. Recovery in 10
      patients and improvement in 3 was obtained and only one patient died. The results
      were compared to the large group of 108 patients treated earlier with other
      drugs. Therapeutic effect was similar in all groups.

PMID- 7566408
TI  - [The method of axonal stimulation (AS) for jitter evaluation in the diagnosis of
      neuromuscular transmission disorders].
AB  - The results of jitter measurements in 15 patients with myasthenia gravis and 10
      control group persons are presented using single fiber emg (SFEMG) method during
      weak voluntary activation and intramuscular AS. The method of AS is described,
      advantages of its use in evaluation of neuromuscular transmission disorders, some
      limitations and technical traps that the investigator encounters are presented.
      Jitter values obtained by both methods are compared and existing differences are
      discussed taking into account two variants of jitter origin.

PMID- 7566409
TI  - [Polyneuropathy in non-Hodgkin lymphoma].
AB  - In a group of patients with non-Hodgkin lymphoma axonal sensorimotor
      polyneuropathy was found in 15%. It appeared in the treated patients, those
      receiving doses of oncovin. Polyneuropathy was not correlated with the type of
      malignancy. Treatment seems to be the important factor which can cause
      polyneuropathy.

PMID- 7566410
TI  - [Visual and somatosensory evoked potentials in the patients with non-Hodgkin
      lymphoma].
AB  - Visual (VEPs) and somatosensory (SEPs) evoked potentials in a group of 33
      patients (mean age 49 years) with non-Hodgkin lymphoma (n-HL) without CNS
      involvement were recorded. There were 24% of patients with pathological VEPs and
      30% of patients with pathological SEPs. Pathological VEPs and SEPs were both
      recorded in 42% of patients. In comparison to the controls the statistically
      significant prolongation of mean latencies of VEPs, SEPs and transit time to
      cortex were found in the group of n-HL patients. These abnormalities were noted
      much more often in patients with long duration of the disease and with
      intermediate type of malignancy. In the untreated patients evoked potentials were
      normal. In 6 patients despite normal neurological status and normal eeg the
      evoked potentials were abnormal. The evoked potentials examination seems to be
      very sensitive method of afferent pathways involvement estimation and can be used
      for diagnosis and prognosis in n-HL patients. This method reveals CNS lesions
      more often than physical examination or eeg.

PMID- 7566411
TI  - [Surgical treatment of brain tumors and intracarnial aneurysms in patients over
      70 years].
AB  - Problem of surgical treatment in the elderly is still discussed in the
      literature. This group of patients needs especially clear criteria of
      qualification for extensive intracranial procedures. The authors present their
      own experience with 35 patients over 70 years old with intracranial tumours and
      intracranial aneurysms treated in Department of Neurosurgery, Warsaw Medical
      School between 1992-1993. Among 11 patients treated conservatively, only 3
      patients were in poor physical state with functional limitation which was a
      contraindication for surgery. Postoperative mortality was 4.2%. On the basis of
      our experience we think that patients over 70 years can be safely operated on
      intracranial lesions and the age is not a contraindication for neurosurgical
      procedures.

PMID- 7566413
TI  - [Application of alteplase in prevention of cerebral vasospasm and its sequelae in
      patients after aneurysmal subarachnoid hemorrhage from ruptured cerebral
      aneurysm].
AB  - 15 patients after SAH from ruptured cerebral aneurysm were operated on within 72
      hours after SAH. During the operation after clipping of aneurysm 10 mg of rtPA
      was administered into basal cisterns, Control group consisted of patients who did
      not receive rtPA. All the patients on the basis of CT scan were classified to III
      grade according to Fisher's classification. Control CT scan revealed dissolution
      of most clots in basal cisterns. In comparison with control group the patients
      who received rtPA rarely experienced radiological signs of vasospasm and delayed
      neurological deficit.

PMID- 7566412
TI  - [The effect of general anesthesia during operation on the central nervous system
      on the pattern of somatosensory evoked potentials -- preliminary communication].
AB  - During monitoring of somatosensory evoked potentials (SEP) during operation for
      intracranial aneurysm disappearance of cortical response can alarm the
      neurosurgeons and suggest the necessity of removal of temporary clipping. As a
      rule, 50% fall of amplitude and/or 10% prolongation of N13-N20 interlatence are
      accepted as a criterion for alarming the operating team. However, a considerable
      part of changes in SEP tracings is caused by factors other than surgical
      manipulations. The purpose of the present study was to determine the effect of
      general anaesthesia on SEP records for their further assessment during monitoring
      of operations for intracranial aneurysm. In 13 patients operated on for that
      reason and in 8 patients undergoing operation for lumbar disc prolapse SEP were
      monitored from over the Erb point, cervical cord (CVII) and parietal area on the
      side of the operation (C3' or C4'). Stimulation was electrical with stimulus
      duration 0.1 ms and 5 c/s frequency. General anaesthesia was found to decrease
      significantly the amplitude of the cortical wave, more evident in the N20-P25
      amplitude, and amounting to about 40%. No statistically significant changes of
      the time of central conduction were found. The observed SEP changes made possible
      in all cases monitoring of operation for intracranial aneurysm.

PMID- 7566414
TI  - [Peripheral nerve tumors: management tactics].
AB  - 29 cases of the peripheral nerve tumours treated in the Department of
      Neurosurgery Military Medical Academy in Lodz between 1971 and 1993 are
      presented. The clinical symptoms, diagnostic methods, methods of operation and
      results are discussed. The differences are stressed, related to histological
      types of tumours. The reason of this management was given.

PMID- 7566415
TI  - [Cerebral blood flow changes after mild head trauma imaging with SPECT HMPAO.
      Preliminary report].
AB  - The authors present 3 cases of mild head trauma diagnosed by CT, EEG and SPECT.
      The results showed that CT scan was negative in all cases while SPECT was
      positive. EEG recording showed changes which seemed to agree with the changes of
      regional cerebral blood flow presented by SPECT. This initial results indicate
      that SPECT HM-PAO within the first two-three days is more sensitive than CT scan
      and detects brain perfusion abnormalities.

PMID- 7566416
TI  - [The role of iron in the pathology of nervous system].
AB  - Iron is one of few metal ions whose role in the central nervous system has
      received little attention, even though it is important in many enzymatic,
      metabolic and structural processes. The brain is rich in iron, and iron is the
      most likely initiator of free oxygen radicals generation. Recent investigations
      have reported that iron-generated free radicals play an important role in the
      pathogenesis of many neurological disorders. Experimental studies have shown that
      iron chelators and free-radical scavengers may have an important therapeutic
      potential in the future trends of treatment. This paper reviewed the current
      state of knowledge in this highly complicated field.

PMID- 7566417
TI  - [Origin of the visual evoked potentials in the light of the conducted research].

PMID- 7566418
TI  - [Spontaneous acute subdural hematoma].
AB  - A rare case of spontaneous acute subdural haematoma is reported. Causes of non
      traumatic subdural haematomas are discussed stressing the necessity of rapid
      surgical intervention.

PMID- 7566419
TI  - [A case of hemorrhagic cerebral abscess with sudden clinical onset].
AB  - A rare case with unfavourable clinical course of haemorrhagic cerebral abscess in
      the parietal region is presented. Attention is drawn to diagnostic difficulties
      in cerebral abscesses with non-typical radiological and clinical picture as well
      as putative mechanisms responsible for haemorrhage within abscess are discussed.

PMID- 7566420
TI  - [Addendum to the paper "Aneurysm of the anterior communicating artery..."
      Neurochirurgia Polska 6/94].

PMID- 7566421
TI  - [Pathogenesis and surgical treatment of syringomyelia].

PMID- 7566422
TI  - [Vestibular nerve section for medically uncontrollable vertigo with Meniere's
      disease].

PMID- 7566423
TI  - [The comparison between adult and pediatric AVMs treated by gamma knife
      radiosurgery].
AB  - More than 290 cases of cerebral AVM had been treated by gamma knife radiosurgery
      since May, 1991, among which ninety-nine cases were angiographically followed up
      for at least one year. Comparison of the results between adult and pediatric AVMs
      were made. There were seventy six adult and twenty three child cases.
      Intracerebral hemorrhages in their past history were found in 73.7% of adult and
      91.3% of child cases respectively, and the rate of intracranial hemorrhages in
      the pediatric group was higher than that in the adult group. The volume of the
      nidus of AVM in both groups was 4.2 ml in adults and 4.8 ml in children. Grade
      III of the Spetzler grading system occupied about 70% of all cases and was the
      most common grade in both groups. Treatment was performed with a mean marginal
      dose of 20.0Gy in adults and 20.5Gy in children. The complete occlusion of the
      nidus was obtained in 45% of the adult group and 74% of the pediatric group one
      year after, and in 81% and 95% respectively two years after the treatment was
      begun. As side effects, these were two rebleedings, one radiation necrosis and
      one radiation-induced edema in adults. However, no side effects were observed in
      children. It is considered that, when using gamma knife radiosurgery, pediatric
      AVMs are more likely to be occluded successfully and safely than adult AVMs.

PMID- 7566424
TI  - [Usefulness of 3-dimensional image analysis of skull base lesions].
AB  - We have evaluated three-dimensional (3D) images of the skull base lesions for
      planning cranial base surgery. Fifty 3D images were reconstructed from computed
      tomographies (CT), and/or magnetic resonance (MR) images or MR angiographic
      images of 30 patients with skull base lesions. These images have provided useful
      information for pre-operative evaluation. The 3D image reconstructed from CT
      provides clear information concerning the bone. Conversely, the 3D image from MR
      images demonstrates soft tissue very clearly, and that from MR angiography
      provides a detailed description of the vasculature. For skull base lesions, it is
      essential to evaluate 3D images from the different modalities, especially CT scan
      and MR image.

PMID- 7566425
TI  - [Diagnosis of ruptured and unruptured cerebral aneurysms with three-dimensional
      CT angiography (3D-CTA)].
AB  - Three-dimensional CT angiography (3D-CTA) is a new, minimally invasive technique
      for the diagnosis of cerebral aneurysms. The purpose of this study is to compare
      the diagnostic value of 3D-CTA for ruptured and unruptured cerebral aneurysms
      with that of MR angiography (MRA) and digital subtraction angiography (DSA).
      Forty-one cases consisting of 11 cases of ruptured aneurysms and 30 cases of
      unruptured aneurysms, with a total of 67 cerebral aneurysms, were included in
      this study. 3D-CTA was performed with a bolus injection of nonionic contrast
      medium on the SOMATOM PLUS-S scanner and the ProSeed Accell scanner. Three
      dimensional images were obtained by both shaded surface reconstruction (SSR)
      method and maximum intensity projection (MIP) method. The CT values of cisternal
      clot in cases of ruptured cerebral aneurysms did not exceed 90HU in any of the
      cases. The effect of SAH was, therefore, eliminated in the SSR images through a
      threshold level processing of a CT value of 150HU. All the cerebral aneurysms
      were visualized by this process. With regard to the detectability of cerebral
      aneurysms, 3D-CTA was able to demonstrate cerebral aneurysms with diameters of
      larger than 1mm as well as giant aneurysms which MRA would sometimes fail to
      reveal. 3D-CTA was superior to MRA and DSA in making diagnosis of small aneurysms
      such as those with diameters of less than 3mm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566426
TI  - [Spontaneous dissecting aneurysm of the superficial temporal artery: a case
      report].
AB  - Aneurysms of the superficial temporal artery are rare, and usually traumatic in
      origin. We present a very rare case of spontaneous dissecting aneurysm of the
      superficial temporal artery in a 46-year-old man. The patient had pulsatile
      headache in the right temporal region, and a pulsatile mass in the same region.
      His headache gradually worsened for which he came to our hospital. On
      examination, there was a pulsatile mass of 1.5cm x 3cm at the right temporal
      region, which disappeared when the main trunk of superficial temporal artery was
      compressed. There was no neurological abnormality. On computed tomographic
      examination, there was a spotty high density area in the right extracranial
      region corresponding to the right superficial temporal artery, which was strongly
      enhanced after contrast medium administration. On MRI examination, the same area
      showed high intensity, but at inner space there was signal loss on T1WI, T2WI and
      PDWI. Angiography showed an aneurysmal dilatation at the right superficial
      temporal artery and both the true lumen and the false lumen were recognized.
      Excision of the aneurysm under local anesthesia was performed. His complaints
      disappeared completely post-operatively, and the skin color of that region
      retained its normal texture. Histopathological examination of the specimen showed
      hypertrophic intima with fibroblasts, and absence of internal elastic lamina.
      There was hematoma outside of the intima, but no deposits of hemosiderin. On
      account of the above findings, the lesion was diagnosed as a spontaneous
      dissecting aneurysm of the superficial temporal artery.

PMID- 7566427
TI  - [Intrasellar arachnoid cyst: a case report].
AB  - Intrasellar arachnoid cyst is very rare. We report a case of intrasellar
      arachnoid cyst. A 44-year-old male was admitted for evaluation of his headache
      and visual disturbance on August 6, 1993. Neurological examination revealed
      bilateral decreased visual acuity and visual field defect. Endocrinological
      examination showed panhypopituitarism. Other neurological findings were normal. X
      ray film of the skull showed a ballooning dilation of the sella turcica with
      thinning of the sellar floor. CT scan showed a cystic lesion with CSF-density
      occupied the sella. After intravenous administration of contrast medium, the cyst
      showed no enhancement. MRI showed the intrasellar mass had the same
      characteristics as the surrounding subarachnoid space. Bilateral carotid
      angiographies demonstrated that the carotid siphons were stretched and displaced
      laterally, and the A1 portions of the anterior cerebral arteries were raised. We
      made a diagnosis of intrasellar cystic lesion. On August 18, the sella turcica
      was opened via the transsphenoidal rhinoseptal approach. The cyst contained CSF
      like fluid, and a part of the cyst wall was resected. The cavity was filled with
      Gelfoam and the sellar floor was repaired with bone flap. Postoperatively, the
      patient's visual disturbance improved, but diabetis insipidus appeared and
      required hormonal replacement. The patient was discharged on September 27 with
      improvement of visual acuity and visual field. Histological examination
      demonstrated that the cyst wall consisted of thick arachnoidal cells with fibrous
      connective tissue. The arachnoidal cells with oval nuclei was stained with
      epithelial membrane antigen. Symptoms, signs and radiological findings of
      intrasellar arachnoid cyst are similar to those of various sellar lesions
      including pituitary adenoma, craniopharyngioma, empty sella, Rathke's cleft cyst,
      epidermoid et al.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566428
TI  - [Surgical treatment of aneurysms at basilar artery and posterior cerebral artery
      associated with moyamoya disease: a case report].
AB  - This report describes a surgical case of basilar-superior cerebellar (BA-SCA)
      junction aneurysm and posterior cerebral artery (PCA) aneurysm associated with
      moyamoya disease. A-38-year-old man in an unconsciousness state and with mild
      left hemiparesis was referred to our hospital. CT scan demonstrated hemorrhage in
      the right basal ganglia. Carotid angiograms showed stenoses at the terminal
      portion of the bilateral internal carotid arteries and moyamoya vessels. Left
      vertebral angiograms showed two aneurysms at the junction of the right superior
      cerebellar artery and the basilar artery and at the P1 portion of the left
      posterior cerebral artery. Two aneurysms were successfully clipped using the
      pterional approach. Bilateral encephaloduroarteriosynangiosis (EDAS) was also
      performed for the treatment of Moyamoya disease. Postoperative angiograms
      revealed complete clipping of the aneurysms and the postoperative course was
      uneventful.

PMID- 7566430
TI  - [Multiple dural arteriovenous shunts presenting as subarachnoid hemorrhage: a
      case report].
AB  - We present here an interesting case of multiple dural arteriovenous shunts (dAVS)
      in different locations at the same time. There have been very few reports on
      multiple dAVS. A 63-year-old man was admitted with a sudden onset of headache and
      vomiting. CT scan showed a typical subarachnoid hemorrhage (Fisher Group 3).
      Cerebral angiogram (6 vessel study) revealed two dural arteriovenous shunts at
      the same time. One was located on the anterior fossa fed by the anterior
      ethmoidal artery, and the other was located on the posterior fossa near the
      marginal sinus fed by the left ascending pharyngeal and occipital arteries. At
      first, transarterial embolization was performed for dAVS located on the posterior
      fossa. Radical operation was performed for both anterior and posterior fossa
      dAVS. Both dAVS had disappeared on postoperative angiograms.

PMID- 7566429
TI  - [Neurofibromatosis associated with multiple intracranial vascular lesions:
      stenosis of the internal carotid artery and peripheral aneurysm of the Heubner's
      artery; report of a case].
AB  - Neurofibromatosis (NF), or von Recklinghausen's disease, is an autosomal dominant
      disorder of both mesoderm and ectoderm dysplasia commonly characterized by
      numerous neurofibromas and cafe-au-lait spots. However, cerebrovascular diseases
      associated with NF are rare, and among them occlusive vascular lesions have
      already been reported in the literature. It is postulated that the pathogenesis
      of the associated vascular lesions may be attributable to the proliferation of
      Schwann cells and the subsequent degeneration in the vessel wall. We documented
      here an uncommon case of NF associated with massive intracerebral hemorrhage
      caused by an aneurysm at the distal portion of the dilated Heubner's artery.
      Intracranial hemorrhage in association with NF is reviewed in the literature, and
      the clinical profiles, type and origin of bleeding, and associated occlusive
      vascular lesions are discussed. A 55-year-old man was admitted to our hospital on
      January 12, 1994, after he had suddenly become comatose. The patient was known to
      be affected by NF from both the family and past histories. On admission, the
      patient demonstrated a decerebrate posture in response to painful stimuli, and
      was then graded as 200 according to the Japan Coma Scale (JCS). CT scan showed a
      significant amount of blood clots present at the base of the right frontal lobe
      and in the lateral and third ventricles. After bilateral ventriculostomies were
      carried out for continuous drainage of bloody cerebrospinal fluid, the patient
      continued to regain partial consciousness to the level of JCS grade 3 until the
      seventh day, when he again suddenly deteriorated and became comatose.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7566431
TI  - [A case of spinal dural arteriovenous fistula associated with normal pressure
      hydrocephalus].
AB  - A 62-year-old male presented with urinary incontinence, gait disturbance and
      dementia for 6 months. Neurological examination revealed severe paraparesis
      (1/5), sensory disturbance below Th10, neurogenic bladder and absence of patellar
      and achilles tendon reflexes. CT scan showed mild brain atrophy and symmetric
      ventriculomegaly with periventricular lucency. Magnetic resonance imaging (MRI)
      showed a linear flow void lesion on the dorsal surface on the back of his swollen
      lower spinal cord. Myelography showed a filling defect and flow disturbance of
      contrast medium in lower thoracic levels, suggesting the presence of adhesive
      arachnoiditis. Spinal angiography demonstrated a fistula formation between dural
      branches of bilateral L4 lumbar arteries and ventral spinal and radicular veins
      on the surface of the dura mater of L4/5 levels. Considering his past history of
      repeated lumbar puncture for tuberculous meningitis at the age of 22 years, a
      diagnosis of acquired spinal dural arteriovenous fistula probably due to repeated
      lumbar puncture was made. Fistulas were embolized with N-butyl cyanoacrylate. And
      normal pressure hydrocephalus was treated by ventriculoperitoneal shunt. Follow
      up CT scans showed a decrease of the size of the ventricular system. Etiology of
      acquired spinal arteriovenous fistula has been reported. In the case, repeated
      lumbar puncture may be a possible cause of arteriovenous fistula in the lower
      spinal dura mater. However, the reason why it took so long to form a fistula
      after the lumbar puncture remains to be elucidated. We suggest that an increased
      protein concentration due to disturbance of cerebrospinal fluid flow might be a
      cause of normal pressure hydrocephalus (NPH).

PMID- 7566432
TI  - [Historical backgrounds of epilepsy surgery: a chronological table].

PMID- 7566433
TI  - Effects of formalin-induced pain on ACTH, beta-endorphin, corticosterone and
      interleukin-6 plasma levels in rats.
AB  - The behavioral and immunoendocrine effects of formalin-induced pain were studied
      in male rats following a subcutaneous injection of formalin (50 microliters;
      0.1%, F01 groups, 10%, F10 groups) or sham injection (control groups). After
      treatment, animals were tested in a transparent open field for either 30 or 60
      min and thereafter sacrificed by decapitation. Plasma was collected for
      adrenocorticotropic hormone (ACTH), corticosterone, beta-endorphin (beta-EP) and
      interleukin-6 (IL-6) determinations. Pain-evoked responses (licking, flexing, paw
      jerk), standard measures of activity (locomotion, rearing, olfactory exploration)
      and self-grooming were recorded. The higher formalin concentration induced
      stronger pain-evoked behavioral responses, paralleled by higher levels of ACTH,
      beta-EP and IL-6, but did not affect the other behavioral parameters. In
      contrast, the lower formalin concentration induced a marked increase in
      locomotion and rearing and a decrease in ACTH levels. In both formalin-injected
      groups, corticosterone did not differ from controls.

PMID- 7566434
TI  - Immunoneutralization of lipocortin 1 reverses the acute inhibitory effects of
      dexamethasone on the hypothalamo-pituitary-adrenocortical responses to cytokines
      in the rat in vitro and in vivo.
AB  - Our recent studies suggest that lipocortin 1 (LC1), a potential mediator of the
      anti-inflammatory, antiproliferative and anti-fever actions of glucocorticoids in
      peripheral tissues, may also contribute to the powerful negative feedback actions
      of the steroids on the hypothalamo-pituitary-adrenal (HPA) axis. In the present
      study we have used (1) an in vitro model to examine the influence of a specific
      neutralizing monoclonal anti-LC1 antibody (anti-LC1 mAb) on the capacity of
      dexamethasone to suppress the cytokine-induced release of the 41-amino acid
      corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) from the
      rat hypothalamus and (2) a passive immunization protocol to assess the
      contribution of LC1 to the inhibitory actions of dexamethasone on the HPA
      responses to immunological (i.p. injection of interleukin 1 beta, IL-1 beta) and
      surgical (laparotomy under ether anaesthesia) stress. In vitro, Il-1 alpha (0.2
      ng/ml), IL-1 beta (0.5 ng/ml), IL-6 (10 ng/ml) and IL-8 (1 ng/ml) each caused
      significant increases in the release of immunoreactive (ir)-CRF-41 and ir-AVP
      from hypothalami removed from rats adrenalectomized 10-12 days before autopsy;
      these responses were readily inhibited by preincubation of the tissue with
      dexamethasone (10(-7) M). The inhibitory actions of the steroid were attenuated
      and, in many instances, abolished by inclusion in the medium of a monoclonal anti
      LC1 antibody (LC1 mAb, diluted 1:15,000); an isotype-matched control antibody
      (antispectrin alpha+beta, diluted 1:15,000) was ineffective in this regard. IL-1
      alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml) and IL-6 (10 ng/ml) also initiated
      similar increases in the release of CRF-41 and AVP from hypothalami from intact
      rats which were effectively blocked by dexamethasone (10(-7) M). However,
      although the inhibitory actions of the steroid on the pharmacologically evoked
      release of CRF-41 were specifically overcome by anti-LC1 mAb (diluted 1:15,000),
      the steroid blockade of AVP release was not. In vivo, rats pretreated with either
      a polyclonal anti-LC1 antibody (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a
      corresponding volume of a nonimmune sheep serum (NSS) responded to immunological
      (IL-1 beta, 3 micrograms/kg i.p.) or surgical (laparotomy under ether
      anaesthesia) trauma with significant increases in the serum ACTH and
      corticosterone concentrations. In the NSS-treated groups, dexamethasone (100
      micrograms/kg), which had no effect on the prestress concentrations of ACTH and
      corticosterone in the blood, completely prevented the HPA responses to both IL-1
      beta and laparotomy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7566436
TI  - Reduced glucocorticoid response to corticotropin secretagogues in the aged
      Sprague-Dawley rat.
AB  - Aging, as well as some frequently associated pathological conditions (depression,
      dementia, Alzheimer's disease, etc.), has been shown to have a profound impact on
      the normal functioning of the hippocampus-hypothalamo-pituitary-adrenocortical
      axis system. The hypothalamo-pituitary-adrenocortical axis in the aged rat is
      characterized by an increase in the basal level of circulating corticosterone, an
      impaired ability to recover from the adrenocortical stress response, and a
      reduced sensitivity to the dexamethasone suppression test. All these alterations
      may arise from a reduced hippocampal negative feedback control of the axis, as
      suggested by the age-dependent loss of hippocampal adrenocorticoid receptors.
      Among the hypothalamic corticotropin secretagogues, corticotropin-releasing
      hormone (CRH) and arginine-vasopressin (AVP) are considered the main
      physiological mediators of hypothalamic control of ACTH release. Thus, we have
      investigated the dynamic and the temporal course of the adrenocortical response
      to CRH and AVP in the aged rat. Freely moving jugular-catheterized male Sprague
      Dawley rats (3- and 24-month-old) were injected with CRH (0.5, 0.05 and 0.01
      microgram/kg i.v.), or AVP (1.0, 0.1 and 0.05 microgram/kg i.v.), or CRH and AVP
      in combination. In addition, adrenocortical sensitivity to corticotropin has been
      studied by injecting ACTH (10 ng/kg i.v.). Our study has (1) indicated that the
      response to ACTH secretagogues is dampened with aging, and (2) shown in the aged
      rat a slower recovery. Moreover, the results had confirmed the age-dependent
      increase in the basal level of corticosterone in the rat, and shown no age
      related differences in the glucocorticoid response to ACTH.

PMID- 7566435
TI  - Evidence that activation of the hypothalamo-pituitary-adrenal axis by electrical
      stimulation of the noradrenergic A1 group is not mediated by noradrenaline.
AB  - The paraventricular nucleus (PVN) of the hypothalamus, where the CRF-containing
      neurosecretory cells controlling the hypothalamo-pituitary-adrenal (HPA) axis are
      located, receives a dense noradrenergic innervation from the A1 group of the
      caudal ventrolateral medulla. In the present study we studied the relationship
      between release of noradrenaline (NA) in the PVN and activation of the HPA axis
      in response to electrical stimulation of the A1 region. In the urethane
      anesthetized male rat, extracellular NA in the PVN was monitored on line by
      electrochemical recording while the activity of the HPA axis was estimated by
      measurement of ACTH in blood samples. A 1 min, 10 Hz stimulation evoked a
      significant increase of extracellular NA in the PVN as well as an ACTH surge in
      blood. The NA and ACTH response evoked by stimulation in the 3- to 14-Hz range
      were found to be frequency dependent. However, whilst the NA response increased
      in an exponential manner with respect to frequency, the ACTH response appeared to
      plateau between 10 and 14 Hz. Specific lesions of the noradrenergic terminals in
      the PVN, by bilateral local administration of 6-hydroxydopamine, markedly reduced
      the ACTH response to stimulation. Intracerebroventricular injection of
      desmethylimipramine, a NA uptake inhibitor, enhanced the increase in
      extracellular NA evoked by submaximal stimulation about 2.5-fold but did not
      modify the corresponding ACTH response. Combined intracerebroventricular
      injection of alpha- and beta-adrenergic antagonists, phentolamine and propanolol
      respectively, did not prevent the ACTH response evoked by stimulation. Following
      stimulation of the caudal ventrolateral medulla, the ACTH response thus appears
      to result from the stimulation of the A1 noradrenergic group projecting to the
      PVN. However, the inability of pharmacological manipulations which enhance or
      block central noradrenergic transmission to influence the ACTH response suggests
      that the noradrenergic endings in the PVN originating from the A1 group use a
      transmitter other than NA to activate the HPA axis at the PVN level.

PMID- 7566437
TI  - Effect of bacterial endotoxin and interleukin-1 on prostaglandin biosynthesis by
      the hippocampus of mouse brain: role of interleukin-1 receptors and
      glucocorticoids.
AB  - There is increasing evidence indicating that the production of cytokines and
      prostaglandins (PG) may be interrelated and is regulated by glucocorticoids (GC).
      In the present study we examined the effect of the bacterial endotoxin
      lipopolysaccharide (LPS) and interleukin-1 (IL-1) on the ex vivo production of
      PGE2 by the dorsal hippocampus of the mouse which contains high levels of
      receptors to IL-1. The roles of IL-1 receptors and GC in the regulation of LPS-
      or IL-1-induced PGE2 production were also studied. In control mice the basal rate
      of PGE2 ex vivo synthesis by slices of dorsal hippocampus was about 250 pg/mg
      protein/60 min. Intraperitoneal injection of either LPS (1-50 micrograms/mouse)
      or IL-1 alpha (50-200 ng/mouse) increased the production of PGE2 in a dose-and
      time-dependent manner. Both LPS and IL-1 alpha induced a maximal 2.5-fold
      increase in PGE2 production at 6 h after the injections. IL-1 beta was less
      effective by approximately 30% as compared to IL-1 alpha. In mice treated with
      the IL-1 receptor antagonist or with the IL-1 antagonist alpha-melanocyte
      stimulating hormone (alpha-MSH), the effects of LPS and IL-1 on PGE2 production
      were completely abolished. Intraperitoneal injections of dexamethasone (DEX) 5 or
      30 micrograms/mouse 2 h prior to the administration of IL-1 alpha significantly
      enhanced the effect of the cytokine on PGE2 production. In mice treated with 100
      micrograms DEX/mouse, the facilitatory effect of the lower DEX does in IL-1
      induced PGE2 production was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566438
TI  - Cytokine regulation of corticosteroid receptors in the rat hippocampus: effects
      of interleukin-1, interleukin-6, tumor necrosis factor and lipopolysaccharide.
AB  - The effects of interleukin-1 beta (IL-1), interleukin-6 (IL-6), tumor necrosis
      factor alpha (TNF) and lipopolysaccharide (LPS) on hippocampal corticosteroid
      receptors were studied in the rat. Type I (mineralocorticoid) and type II
      (glucocorticoid) receptors were measured in hippocampal cytosolic fractions with
      the radioligand binding technique, using 3H-corticosterone and 3H-RU 28362,
      respectively. LPS, administered intraperitoneally (50 micrograms/kg 8 h before
      sacrifice or 100 micrograms/kg injected twice, 16 and 8 h before sacrifice) to
      rats which had been previously adrenalectomized to allow for clearance of
      endogenous corticosterone, did not modify either type of corticosteroid receptors
      in the hippocampus. IL-1, IL-6, TNF or saline were injected
      intracerebroventricularly (50 ng/rat) and the animals were killed 3 h after. Type
      I receptors were not affected by any of the cytokines studied. Moreover, no
      changes in type II receptors were observed after IL-1 or IL-6 administration. In
      contrast, hippocampal type II receptors were dramatically decreased after the
      injection of TNF. The TNF-induced downregulation of type II receptors was
      secondary to a marked decrease in the affinity of the receptors (Kd increased 7.2
      fold), accompanied by a 51% decrease in receptor number (Bmax). These results
      emphasize the important role played by TNF in the modulation of the hypothalamic
      pituitary-adrenal axis during immune/inflammatory processes and extend the
      central sites of action of this cytokine to the corticosteroid receptors of the
      hippocampus.

PMID- 7566441
TI  - Differences in arylalkylamine N-acetyltransferase activity between inflammatory
      disease-susceptible Lewis and -resistant Fischer rats.
AB  - Lewis (LEW/N) and Fischer (F344/N) rats are histocompatible inbred strains
      characterized, respectively, by susceptibility and resistance to inflammatory
      disease. The susceptibility of LEW/N rats to inflammation has been associated
      with deficient corticotropin-releasing hormone (CRH), ACTH, and corticosterone
      responses to inflammatory stimuli, specifically attributed to a global impairment
      in hypothalamic CRH neuron function. In contrast to the LEW/N rats, F344/N rats
      demonstrate an intact hypothalamic-pituitary-adrenal (HPA) axis. Melatonin, a
      neurohormone initially isolated in the pineal gland, has been implicated with
      inhibition of the HPA axis. To investigate melatonin synthesis and secretion in
      LEW/N and F344/N rats, we examined the diurnal activity of pineal arylalkylamine
      N-acetyltransferase (NAT1), the rate-limiting enzyme in melatonin biosynthesis,
      which demonstrates circadian rhythmicity, as well as the diurnal levels of serum
      melatonin, in both strains. Arylamine N-acetyltransferase (NAT2), a related
      enzyme activity, thought not to be regulated in a circadian manner, was examined
      as a control of NAT1 activity. Pineal NAT1 activity peak was observed later and
      reached significantly higher levels in LEW/N than in F344/N rats. Serum melatonin
      levels reflected the circadian pattern of the NAT1 activity, without, however,
      showing any quantitative differences between the two strains. Time-course of
      pineal NAT1 activity response to beta-adrenergic stimulation was parallel in the
      two rat strains, whereas the magnitude of the response as greater in LEW/N than
      in F344/N rats. No circadian or major quantitative differences in NAT2 activity
      were found between the two strains. Size-exclusion HPLC chromatograms of NAT1
      activity revealed similar patterns in both rat strains.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7566440
TI  - Increased number of corticotropin-releasing hormone expressing neurons in the
      hypothalamic paraventricular nucleus of patients with multiple sclerosis.
AB  - Observations in experimental allergic encephalomyelitis (EAE), a model for
      multiple sclerosis (MS), have indicated that a low activity of the hypothalamo
      pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in
      rat strains and that elevated corticosteroid levels are necessary for spontaneous
      recovery from EAE. The HPA axis activity is regulated by both corticotropin
      releasing hormone (CRH) and arginine vasopressin (AVP). Both types of neurons are
      localized in the paraventricular nucleus (PVN) of the hypothalamus. We determined
      the number of immunocytochemically identified CRH-immunoreactive (CRH-IR) and AVP
      immunoreactive (AVP-IR) neurons in the PVN of the human hypothalamus of 8 MS
      patients, aged 34-63 years, and 8 age-matched control subjects without any
      primary neurological or psychiatric disorders, aged 30-59 years. In addition, the
      number of oxytocin (OXT) immunoreactive (OXT-IR) neurons was determined, since
      these neurons innervate brain stem nuclei and might thus be related to autonomic
      disturbances in MS. In MS the staining intensity for AVP was clearly lower and
      for OXT slightly lower. For CRH, the staining intensity was similar in both
      groups, and, moreover, in MS patients the number of CRH-IR cells in the PVN was
      found to be about 2.4 times higher than that in the control group. The number of
      OXT-IR or AVP-IR cells in the PVN of MS patients was not significantly different
      from that of the control group. Our results point to an activation of the
      neuroendocrine HPA axis which may be compatible with the idea that the HPA axis
      is involved in recovery from MS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566439
TI  - Production of systemic and hypothalamic cytokines during the early phase of
      endotoxin fever.
AB  - Changes in concentrations of cytokines in plasma and in hypothalamic push-pull
      perfusates of guinea pigs were measured within the 1st hour after intramuscular
      injections of bacterial lipopolysaccharide (LPS; Escherichia coli, 20
      micrograms/kg) or solvent (0.9% saline). In control animals injected with
      solvent, interleukin (IL)-1 and tumor necrosis factor alpha (TNF-alpha) were not
      detectable in plasma. Only IL-6 was present in picogram quantities. Within 45 min
      after injection of LPS, the concentrations of IL-1, TNF-alpha, and IL-6 increased
      in the plasma: by several orders of magnitude for TNF-alpha and about tenfold for
      IL-G. Picogram amounts of biologically active IL-1 were detected in plasma after
      injection of LPS. No steady state levels of systemic cytokines were reached
      during the experimental period. In hypothalamic perfusates of animals injected
      with the solvent, no IL-1 was detectable. TNF-alpha could be detected at higher
      concentrations than IL-6. IL-6 was detectable at tenfold lower concentrations
      than in the plasma. In animals injected with LPS, the hypothalamic concentration
      of IL-6 started to increase during the period 15-30 min and the concentrations of
      TNF-alpha during the period 30-45 min after LPS injection. The concentrations of
      IL-6 increased by 300-400% and did not exceed picogram values. No progressive
      increase of hypothalamic levels of these cytokines was observed during the time
      course of the experiment. The method used did not detect any changes in the
      amount of biologically active IL-1 in hypothalamic perfusates of LPS-treated
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566442
TI  - Impaired hypothalamo-pituitary-adrenal axis function in Swiss nude athymic mice.
AB  - Various evidence suggests a bidirectional circuit between the immune and
      neuroendocrine systems. Because of the well-known role of the thymus in the
      regulation of the immune function, we designed this study to determine whether
      the lack of thymus may affect hypothalamo-pituitary-adrenal (HPA) axis activity
      by using both in vivo and in vitro paradigms in Swiss nude (athymic) and BALB/c
      (normal) mice. Eight-week-old female mice of both strains were used to study: (a)
      the in vivo response of the HPA axis to various stress stimuli acting at either
      hypothalamic (ether vapor inhalation, insulin administration), pituitary (CRH
      injection) or adrenal (ACTH treatment) level and (b) the in vitro response of
      pituitary and adrenal cells to CRH and ACTH stimulation, respectively. The
      results indicate that: (1) basal plasma ACTH levels were significantly (p < 0.05)
      higher in Swiss nude than in BALB/c mice, whereas basal plasma corticosterone (B)
      concentrations were similar in both strains of mice; (2) the stress-induced
      release of ACTH and B in plasma were significantly (p < 0.05) lower in Swiss nude
      than in BALB/c mice, regardless of the stimulus applied; (3) the in vitro
      pituitary response to CRH and the adrenal response to ACTH were significantly (p
      < 0.05) lower in Swiss nude than in BALB/c mice, whereas (4) hypothalamic CRH and
      pituitary ACTH contents were similar in both strains, adrenal B concentration was
      significantly (p < 0.05) lower in athymic mice; in addition, the nude mice
      adrenal glands were larger than those of BALB/c animals, due to marked
      hypertrophy of the zona fasciculata.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566445
TI  - The neuropathology of Rett syndrome--overview 1994.
AB  - The syndrome which Andreas Rett and Bengt Hagberg first brought to our attention
      has been observed for eighteen years. It appears to be unlike any other disease
      of childhood. The original descriptions of Rett syndrome, as being autistic,
      degenerative and progressive are now, based on longitudinal observations, being
      questioned. In this paper the morphologic changes in the nervous system in Rett
      syndrome are summarized. The evidence against a degenerative process are
      presented, and the alternations are considered, along with the clinical features
      in terms of a possible arrest of brain development.

PMID- 7566443
TI  - In vivo and in vitro flow cytometry comparative analysis of somatostatin-positive
      cells in the pineal gland of the neonatal rat.
AB  - Flow cytometry was used for comparative in vivo and in vitro analysis of cell
      populations staining positively for somatostatin. Experiments were carried out
      with pineals obtained from neonatal, 8- and 15-day-old rats. Pineal cells were
      obtained by dispersion with collagenase and then processed in a flow cytometer or
      maintained in culture for 1 or 2 weeks. Identification of somatostatin
      immunopositive cell populations was performed using a polyclonal somatostatin
      antibody and confirmed by indirect immunostaining of cytospun smears with the
      avidin-biotin-peroxidase method. In vivo, the percentage of somatostatin-positive
      cells was 60.6 +/- 4% in neonatal pineals and declined to 22.2 +/- 11% in 15-day
      old animals (p < 0.04). The density of peptide immunostaining decreased in 8-day
      old animals but recovered to the neonate levels in 15 day-old animals;
      homogeneity in the immunopositive population increased with age. Maintenance in
      culture for 1 week resulted in an increase in positive somatostatin staining in
      animals of 8 and 15 days with no changes in neonates; however, after 2 weeks of
      culture, the percent of immunopositive cells decreased from 53.3 +/- 6 to 12.2 +/
      4% in the older animals and remained unchanged in neonates. We conclude that
      somatostatin is found in pinealocytes and shows a declining pattern during the
      perinatal period; this probably implies that the peptide plays a paracrine role
      important for cell differentiation in these young animals, since maximal
      cellularity and a high mitotic index occur within the first 3 days of life, and
      pineal cell differentiation is completed before the end of the third week of
      extrauterine life.

PMID- 7566444
TI  - Effects of sex hormones on the pineal response to isoproterenol and on pineal
      beta-adrenergic receptors.
AB  - Several studies have shown sex hormone effects on pineal function. In order to
      clarify the role of adrenergic mechanisms in these effects, we investigated the
      pineal response to adrenergic stimulation and pineal beta-adrenergic receptors
      following castration and/or sex hormone treatment in 2-month-old male and female
      Sprague-Dawley rats. The urinary 6-sulphatoxymelatonin (aMT6s) response to
      isoproterenol (ISO) was compared in castrated and sham-operated animals.
      Ovariectomy caused an increase and orchiectomy a decrease in ISO-induced urinary
      aMT6s excretion. The melatonin response to ISO was examined in pineal glands and
      serum samples obtained from castrated, sex-hormone-treated castrated and sham
      operated rats. Consistently, ovariectomy increased pineal and serum melatonin
      responses to ISO, while orchiectomy decreased the responses; oestradiol and
      testosterone treatments, respectively, reversed these effects. 3H
      dihydroalprenolol binding was measured in single pineal glands from castrated,
      sex-hormone-treated castrated and sham-operated rats. Ovariectomy increased the
      density of beta-adrenoceptors, whereas orchiectomy decreased the density;
      oestradiol and testosterone replacement, respectively, blocked these effects. No
      significant effect on receptor Kd values was found. These data suggest that sex
      hormones regulate pineal melatonin production by modifying beta-adrenergic
      mechanisms.

PMID- 7566446
TI  - Microscopic observations of the brain in Rett syndrome.
AB  - Rett syndrome (RS) is a clinically defined disorder which appears to be unique to
      females and which is associated with apparent loss of cognitive and motor skills
      early in life. Using the technique of gapless serial section, microscopic
      analysis of the brains from three cases of RS and identically processed age
      matched controls was conducted to determine the nature and extent of cerebral
      abnormality in this disorder. Small neuronal cell size and increased cell packing
      density were observed throughout the brain in all three cases, without evidence
      of gliosis or active degeneration. These findings are consistent with a
      curtailment of brain development which may begin before birth. Further, the brain
      abnormalities in RS appear to be more diffuse than previously appreciated and are
      in accord with the widespread neurological symptoms characteristic of this
      disorder.

PMID- 7566447
TI  - Abnormal expression of microtubule-associated protein 2 (MAP-2) in neocortex in
      Rett syndrome.
AB  - Immunocytochemical evaluations of the neocortex of three classical Rett syndrome
      (RS) individuals revealed a selective abnormality in the expression of
      microtubule-associated protein 2 (MAP-2). MAP-2 immunoreactivity (ir) was reduced
      throughout the neocortex of all three RS cases with a reversal of the normal
      pattern of more intense staining in deep cortical layers. This anomaly was
      selective for MAP-2 because nonphosphorylated neurofilament (SMI-32) labeling of
      deep pyramidal neurons and calbindin (CaBP)-stained GABAergic cells remained
      unchanged. Moreover, MAP-2 ir was virtually undetected in white matter while
      GABAergic and, particularly, peptidergic (neuropeptide Y: NPY) profiles were
      easily recognized. These results demonstrate a marked disruption of a major
      cytoskeletal component in neocortex in RS which seems to affect, predominantly,
      pyramidal projection and white matter neurons. MAP-2 expression appears early in
      neuronal maturation of the neocortex, particularly in the subplate region, the
      future superficial white matter, suggesting that these reported abnormalities in
      RS represent a developmental disturbance. Considering that MAP-2 expression is
      regulated by several neurotransmitter systems in adult cerebral cortex,
      particularly dopaminergic and cholinergic afferents that are deficient in RS,
      these neurochemical alterations could be related to this anomalous MAP-2
      expression.

PMID- 7566448
TI  - Preliminary evidence for neurodegenerative changes in the substantia nigra of
      Rett syndrome.
AB  - Rett syndrome (RS), which affects approximately 1 in 10,000 young females, is
      characterized by cognitive deterioration, ataxia, apraxia, rigidity, and
      stereotyped hand movements. Neuropathological features include reduction in brain
      size and hypopigmentation of neurons of the substantia nigra pars compacta
      (SNpc). Neurochemical and imaging studies support nigrostriatal involvement. The
      results of our preliminary studies show abnormalities in neurons of the
      substantia nigra (SN), including decreased numbers of neurons, ubiquitin-stained
      neuronal inclusion bodies, decreased immunostaining for transmitter markers, and
      evidence of cell death using terminal deoxynucleotidyl transferase (TDT)-mediated
      dUTP-biotin nick end labeling (TUNEL), which labels fragmented intranucleosomal
      DNA. These preliminary data represent the first evidence for cell death in RS.

PMID- 7566450
TI  - Alterations in dopaminergic function in Rett syndrome.
AB  - Rett syndrome is a neurological disorder associated with cortical atrophy,
      stereotyped hand movements, dementia, and extrapyramidal dysfunction. Endogenous
      levels of dopamine and its metabolites are decreased throughout the neocortex and
      basal ganglia and the number of dopamine type 2 receptors are decreased in the
      putamen. The present study investigated changes in dopamine uptake sites and
      dopamine type-1 receptors in the brains of eleven Rett syndrome patients (4-30
      yrs) and ten normal female controls (2.5-20 yrs). The number of dopamine type 1
      receptors within the caudate nucleus were unchanged. The density of dopamine
      reuptake sites were unchanged in the cingulate and midfrontal gyri but decreased
      within the caudate nucleus and putamen. The results of the present study suggest
      that: 1) in the basal ganglia of Rett syndrome patients, dopamine receptive
      neurons are intact whereas the number and activity of dopamine terminals are
      decreased, and 2) in the midfrontal and cingulate cortex, dopaminergic neuronal
      activity may be increased in order to compensate for fewer terminals that contain
      less dopamine.

PMID- 7566449
TI  - Neurobiology of Rett syndrome.
AB  - From a neurobiologic perspective, Rett syndrome appears to disrupt the growth of
      axonodendritic connections among neurons. The cell packing density within the
      grey matter is increased but the total number of neurons is relatively normal,
      except for selected neuronal populations such as the nucleus basalis of Meynert
      (NBM) and the substantia nigra. Neurochemical assays of postmortem brain from
      patients with Rett syndrome patients demonstrate reductions in choline
      acetyltransferase (ChAT), the acetylcholine synthetic enzyme localized in NBM
      nerve terminals. In an animal model, early postnatal injury to the cholinergic
      pathways projected from the NBM causes permanent disruption of developing
      cholinergic neurons and a behavioral disorder on maze testing. The results
      suggest a mechanism by which early deficits in cholinergic and dopamine neurons
      projecting to the cerebral cortex from the brainstem and basal forebrain could
      disrupt axonodendritic development in the cerebral cortex. Studies in our
      laboratory are examining the mechanisms for these effects as well as the
      distribution and densities of neurotransmitter receptors in postmortem brains
      from Rett patients.

PMID- 7566451
TI  - Cerebral proton magnetic resonance spectroscopy in Rett syndrome.
AB  - Combined MRI/MRS studies were performed in 9 girls with Rett syndrome of
      different ages. NAA, as marker of neuronal tissue, was found to decrease with
      increasing age. There was no evidence for a defective energy metabolism. The data
      point towards a probably secondary degenerative process in the pathogenesis of
      Rett syndrome.

PMID- 7566452
TI  - Molecular and neurobiology aspects of Rett syndrome.

PMID- 7566453
TI  - Clinical delineation of Rett syndrome variants.
AB  - The broad clinical variety within the Rett syndrome (RS) concept is emphasized. A
      model recently presented for delineation of atypical Rett variants is reviewed.

PMID- 7566455
TI  - Early clinical signs in the Rett disorder.
AB  - This review of the period from birth until the end of regression in classic Rett
      syndrome (RS) is based on personal experience of more than 600 cases over 12
      years including video material on 42 cases showing behaviour before regression. A
      period of undoubted developmental progress followed by loss of skill is apt to
      persuade the physician that a fresh toxic or infective insult has afflicted a
      normal child but close scrutiny of classic Rett syndrome cases indicates that the
      cognitive and motor problems of the disorder are detectable from birth, that a
      developmental ceiling limits progress and that the timing and nature of the
      regression event and subsequent behaviour of the child indicate inherently
      defective central receptive processing with a highly specific profile. A model
      illustrates how the characteristic disturbances may express incompetent higher
      control. The robust mid infancy level skills of the Rett child and woman deserve
      careful analysis and offer potential for therapy. Metabolic and immune sequelae
      may occur as the developmental defect becomes manifest and such cascade events
      demand careful evaluation and offer further opportunities for intervention.

PMID- 7566454
TI  - Rett syndrome studies of natural history and search for a genetic marker.
AB  - The commonly held notion that Rett syndrome (RS) is a neurodegenerative disorder
      with normal early development was examined by an epidemiological survey and
      review of medical records and serial neurological and development evaluations. In
      some subjects, deviance from normal development was evident from the perinatal
      period, and gradually became more prominent with age. These findings are
      convincing when seen in conjunction with a reduction in velocity of brain growth,
      as early as 2-4 months of life, well before the recognition of gross neurological
      deficits. Neurodevelopmental evaluations provide no indication that there is
      progressive loss of adaptive behaviors, or communication skills to indicate a
      neurodegenerative process. Taken together with the known neuropathological and
      neurochemical changes in RS brain we hypothesize that RS is a neurodevelopmental
      disorder, which has a genetic basis, and affects subsets of neurons and their
      connections during a period of vigorous brain growth, when synapse formation and
      pruning are at a peak. Studies of mitochondrial (mt) DNA in brain to understand
      the genetic mechanisms underlying matrilineal inheritance in the few familial
      cases, and mt structural and enzyme deficiencies have been unrevealing to date.

PMID- 7566456
TI  - Short fourth toes in Rett syndrome: a biological indicator.
AB  - Classic Rett syndrome is now well-known as a non-dysmorphic developmental
      disorder almost certainly of genetic origin. Short 4th toe (uni- or bi-lateral)
      is inherited as an autosomal dominant with 27% penetrance and is found also in
      certain dysmorphic syndromes. Having observed the anomaly in several Rett cases,
      we examined a cohort of classic Rett people at advisory clinics and all the
      residents in an adult learning disabled hospital in order to determine the
      significance of the association. Among the Rett clinic group 28 of 137 showed the
      anomaly (20%). Among the heterogeneous hospital group it was found in 19 of 526
      people, 9 of 206 females (4%) and 10 of 320 males (3%). Rett syndrome was present
      in 7% of all the women (14 of 206 women). Four of the Rett women showed the toe
      anomaly (28% of the Rett cases). The anomaly was found in 4 men and 4 women with
      Down syndrome, representing 16% (8 of 49). Diagnoses in other men with the
      anomaly included foetal alcohol syndrome, toxoplasmosis, 18/2 translocation and
      birth injury. The only other woman with the anomaly was profoundly disabled with
      short limbs. The strong positive association of the anomaly with Rett syndrome
      and Down syndrome throws new light on the developmental processes affected by
      these diseases.

PMID- 7566457
TI  - Management of Rett syndrome: a ten year experience.
AB  - Over the past 10 years (1983-1993) multidisciplinary team at the Child
      Development and Rehabilitation Center has diagnosed and evaluated 60 females with
      Rett syndrome aged 13 months to 43 years. Experience with comprehensive
      management is discussed with focus on feeding difficulties, communication needs,
      hand function, scoliosis, and deformities. Clinical and radiological assessment
      of feeding problems is important in deciding whether therapy will allay symptoms
      or a gastrostomy is indicated. Hand use can be facilitated with appropriate
      intervention, and a coordinated effort with a communication specialist can
      develop systems for environmental access. Aggressive physical therapy has been
      very effective in preventing progression of scoliosis and avoiding surgery.
      Asymmetrical function is commonly recognized in ambulatory females, and is of
      neurogenic origin. Psychosocial support and educational plan attempts to
      collaborate with community services and resources.

PMID- 7566458
TI  - Commentary: the challenge of Rett syndrome.

PMID- 7566459
TI  - Male Rett variant.
AB  - Seven cases of male Rett-like syndrome have been reported in the literature, so
      far. Another case of a 7-year-old-boy is presented who shows the phenotype of
      classical Rett syndrome.

PMID- 7566460
TI  - The Rett condition--broad clinical variability--a case report over three decades.
AB  - A forme fruste Rett variant female with partially preserved speech remnants is
      described. She was first seen by the author at an age of 4 years. She then
      presented with an unspecific syndrome of moderate mental retardation. At follow
      up when aged 32 she had successively through the years developed a number of Rett
      characteristic abnormal behavioural patterns and neurologic deviations, together
      convincingly indicating a Rett syndrome. However, this has been discrete and
      atypical in original presentation and first apparent in the long term clinical
      profile. It is underlined that a whole battery of Rett peculiarities appearing
      with age should be present to allow diagnostic accuracy.

PMID- 7566461
TI  - Gross motor disability and head growth in Rett syndrome--a preliminary report.
AB  - Growth of head circumference was measured in 99 RS girls and compared to gross
      motor function. The degree of head growth deceleration correlated to the severity
      of gross motor disability at 12 years of age.

PMID- 7566462
TI  - Rett syndrome--distribution of phenotypes with special attention to the preserved
      speech variant.

PMID- 7566463
TI  - Current status of genetic research in Rett syndrome.
AB  - Rett syndrome is a progressive neurological development syndrome. Evidences for a
      genetic transmission, but no conclusive data which entirely support the X
      chromosome involvement, exist. The chromosomal region 11p14-pte has been
      investigated with polymorphic markers and genes in the region have been
      sequenced. No sequence divergencies were detected.

PMID- 7566464
TI  - Oxidative metabolism in Rett syndrome: 1. Clinical studies.
AB  - The etiology of Rett syndrome (RS) remains a mystery. The clinical phenotype has
      similarities to that of patients with mitochondrial defects of oxidative
      metabolism. There is evidence of lactate and pyruvate elevations in blood and CSF
      in some patients. Over the last 10 years we have studied girls with RS looking
      for evidence of a defect in oxidative metabolism. We present data on lactate and
      pyruvate blood measurements in 30 patients with RS with repeated measurements
      performed over time in many. Taken as a whole the means of measurements of
      lactate and pyruvate fall within the control range, however, individual patients
      have marked elevation of both lactate and pyruvate with considerable fluctuation
      over time. Nine girls with typical RS were studied in detail using a clinical
      protocol designed to identify disorders of oxidative metabolism. These patients
      underwent fasting for 24 hours, glucose loading and alanine loading tests. Seven
      girls had skin and muscle biopsies performed. One patient admitted with
      particularly high blood lactate levels underwent hourly blood collections over a
      24 hour period during which state of alertness was noted and respiratory
      monitoring was performed. In this patient serial blood sampling for lactate
      performed. In this patient serial blood sampling for lactate performed with
      oxypneumocardiogram recording demonstrated a fall in plasma lactate to normal
      levels during sleep when the respiratory pattern was normal. Such fluctuations of
      plasma lactate apparently correlated with sleep/wake state and respiration
      suggest that in some patients with RS lactate elevations may arise from
      respiratory abnormalities. Other positive findings included prediabetic glucose
      responses in three girls. Ammonia levels following alanine loading were normal in
      all patients.

PMID- 7566465
TI  - Oxidative metabolism in Rett syndrome: 2. Biochemical and molecular studies.
AB  - In an attempt to identify a possible defect of mitochondrial metabolism in Rett
      syndrome we studied 9 girls with typical Rett syndrome using a clinical protocol
      designed to identify disorders of oxidative metabolism. One girl, (RO) had marked
      lactic acidemia. Biochemical studies on samples from these patients included
      leukocyte pyruvate carboxylase assay, serum biotinidase and skin fibroblast
      pyruvate production, pyruvate dehydrogenase, citrate synthetase and 2
      oxoglutarate dehydrogenase assay. Muscle electron transport activities were
      studied on samples from 4 typical Rett patients including RO. Mitochondrial DNA
      (mtDNA) mutational analysis for the np3243 MELAS mutation, the np8993 NARP
      mutation, the np8344 MERFF mutation and the 4977 kb common deletion found in
      Kearns-Sayre syndrome and aged tissues were tested for in 1 of the muscle samples
      and 2 blood samples from typical Rett patients. Western blotting of electron
      transport complex III was performed on mitochondrial samples obtained from
      autopsy brain tissue in 2 Rett patients and compared to pediatric control brain
      samples. No abnormalities were found in blood biotinidase or pyruvate
      carboxylase. Western blotting of 2 Rett brain mitochondrial samples for complex
      III appear normal. Pyruvate consumption in medium from 8 Rett fibroblast lines
      grown with and without dichloroacetate (DCA) showed a normal fall in pyruvate
      suggesting normal pyruvate dehydrogenase activity in these cells, however the
      fibroblasts from patient RO had a high pyruvate production in culture. Pyruvate
      dehydrogenase, 2-oxo-glutarate dehydrogenase and citrate synthetase activities in
      8 Rett fibroblast lines were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566466
TI  - Adrenergic receptor signal transduction and regulation.

PMID- 7566467
TI  - Action on noradrenergic transmission of an anticholinesterase: 9-amino-1,2,3,4
      tetrahydroacridine.
AB  - The mechanism by which 9-amino-1,2,3,4-tetrahydroacridine (THA) inhibits beta
      adrenoceptor linked cyclic AMP formation and its possible relationship with the
      cholinergic system were studied. In addition, the effect of THA on alpha 1
      adrenoceptor coupled transduction systems was also investigated. THA was not able
      to influence the concentration-response curve for forskolin indicating that it is
      not acting on the catalytic subunit of the adenylate cyclase complex. On the
      other hand a cholinergic component seems to participate in the action of THA on
      beta-adrenoceptor stimulated adenylate cyclase activity since the blockade of
      muscarinic receptors with atropine (10 microM) partially prevented the reduction
      in cyclic AMP formation attained by THA in the hippocampus, in isoprenaline
      stimulated conditions. This effect is not reproducible by another potent
      anticholinesterase physostigmine. Moreover, THA at concentrations up to
      micromolar did not affect alpha 1-adrenoceptor stimulated cyclic AMP formation or
      phosphoinositide hydrolysis. In conclusion, the neuropharmacological profile of
      THA is not to be restricted to the cholinergic system and its effectiveness in
      improving age-associated cognitive deterioration may involve an action on the
      beta-adrenoceptor coupled signal transduction system. Moreover, the action of THA
      on the beta-adrenergic and cholinergic systems in the brain could be relevant to
      the amelioration of cognitive deterioration and could lead to the development of
      new therapeutic strategies.

PMID- 7566468
TI  - Effects of the 5-HT1D receptor antagonist GR127935 on extracellular levels of 5
      HT in the guinea-pig frontal cortex as measured by microdialysis.
AB  - The involvement of 5-HT1D receptors in the regulation of 5-HT release in the
      guinea-pig brain was examined using the novel 5-HT1D receptor blocking drug
      GR127935. Levels of 5-HT were measured in frontal cortex of anaesthetized guinea
      pigs using microdialysis. The infusion of GR127935 (100 nM) through the dialysis
      probe into frontal cortex caused a significant increase (61 +/- 8%) in cortical
      extracellular levels of 5-HT. The increase was transient (approximately 40 min)
      even in the continuous presence of GR127935. The transient increase was abolished
      by tetrodotoxin (1 microM). The 5-HT1 receptor agonist GR46611 (10 mg/kg s.c.)
      caused a significant and sustained (> 100 min) reduction in extracellular levels
      of 5-HT (65 +/- 5%). This response was abolished in animals pre-treated with
      GR127935, 0.05 mg/kg i.p. Paradoxically, systemic administration of higher doses
      of GR127935 (0.1-1 mg/kg i.p.) in naive anaesthetized guinea-pigs caused
      significant and sustained (> 120 min) decreases (> 65%) in cortical levels of 5
      HT. The increase in extracellular 5-HT seen following infusion of GR127935 into
      frontal cortex may be due to GR127935 blocking 5-HT terminal autoreceptors
      causing a subsequent increase in the outflow of 5-HT from pre-synaptic terminals.
      This conclusion is supported by the ability of GR127935 to block the decrease in
      5-HT induced by the 5-HT1 receptor agonist GR46611.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7566469
TI  - The effects of GR127935, a putative 5-HT1D receptor antagonist, on brain 5-HT
      metabolism, extracellular 5-HT concentration and behaviour in the guinea pig.
AB  - Studies of neurotransmitter release in guinea pig and human brain indicate that
      the 5-HT terminal autoreceptor is the 5-HT1D subtype and that it regulates the
      depolarization evoked release of 5-HT. Thus, blockade of the terminal 5-HT
      autoreceptor should enhance 5-HT release in vivo. In the present study, we have
      used the recently described, selective and potent 5-HT1D receptor antagonist,
      GR127935, to determine if blockade of the terminal 5-HT autoreceptor enhanced 5
      HT neurotransmission in the guinea pig. Neurochemical studies showed that
      GR127935 (0.1, 0.3 and 1.0 mg/kg i.p.) significantly increased 5-HT metabolism in
      forebrain regions but not in the raphe nucleus of the guinea pig. However, using
      in vivo dialysis, GR127935 did not significantly increase cortical 5-HT efflux
      when given either systemically (1 and 5 mg/kg i.p.) or by infusion via the probe
      directly into the cortex (10, 33 and 100 microM). Fast cyclic voltammetry studies
      in the guinea pig dorsal raphe slice in vitro failed to observe any significant
      effects of GR127935 (0.01-1 microM) on electrically evoked 5-HT release.
      Behavioural studies in the guinea pig were also unable to demonstrate any effects
      of GR127935 (0.1-3.0 mg/kg i.p.) per se or in combination with the 5-HT precursor
      5-hydroxytryptophan. Taken together, results from the present neurochemical and
      behavioral studies in the guinea pig provide little substantial evidence that
      blockade of the terminal 5-HT autoreceptor following the acute administration of
      GR127935 increased brain 5-HT neurotransmission in vivo.

PMID- 7566470
TI  - Further characterization of the binding of the adenosine receptor agonist [3H]CGS
      21680 to rat brain using autoradiography.
AB  - 2-[p-(2-carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoadeno sine (CGS
      21680) is considered a selective ligand for adenosine A2A receptors, which are
      known to be enriched in striatum and olfactory tubercle. We have investigated the
      characteristics of [3H]CGS 21680 binding in several brain regions using
      quantitative autoradiography. In agreement with previous data the radioligand was
      found to label the caudate-putamen, accumbens nucleus, olfactory tubercle and
      globus pallidus, but also many other structures, e.g. cerebral and cerebellar
      cortex, hippocampus, thalamus and some brainstem nuclei, were labelled. Cortical
      and striatal binding of [3H]CGS 21680 was unaltered by high concentrations of the
      adenosine transport inhibitor dipyridamole or the phosphodiesterase inhibitor
      rolipram but was displaced by 1,3-diethyl-8-phenylxanthine, the A2 selective
      adenosine antagonist CP 66,713, and the A2A selective agonist SHA 118. These
      three agents were approximately equipotent in striatum, cortex and hippocampus.
      The A2 selective agonist CV 1808 was a 4-5 times more potent displacer in cortex
      and hippocampus than in the striatum. [3H]CGS 21680 binding was strongly
      magnesium-dependent in all the studied brain regions, in contrast to the binding
      of adenosine A1 agonists. The binding of [3H]CGS 21680 to cerebral cortex and
      hippocampus, but not the binding to striatum, was displaced by the adenosine
      receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine in nanomolar
      concentrations. The present study provides evidence that in cerebral cortex and
      hippocampus, most of the [3H]CGS 21680 binds to a receptor site that is distinct
      from the striatal A2A receptor and the classical adenosine A1 receptor and may
      represent a hitherto unrecognized binding site.

PMID- 7566473
TI  - Effects of remacemide and its metabolite FPL 12495 on spike-wave discharges,
      electroencephalogram and behaviour in rats with absence epilepsy.
AB  - The effects of the anti-convulsant drug remacemide and one of its active
      metabolites FPL 12495 were examined in a genetic model for generalized absence
      epilepsy, the WAG/Rij strain of rats. Number, mean and total duration of spike
      wave discharges were measured following oral administration of remacemide and FPL
      12495, together with parameters of background electroencephalographic activity
      (EEG) and spontaneous behaviour in the recording cage. A decrease in the number
      of the spike-wave discharges was found after remacemide administration. At the
      highest dose there was near total suppression of the spike-wave discharges. There
      were no important effects on behaviour and on spectral content of the background
      EEG, suggesting that remacemide has little side effects. A decrease in the number
      of spike-wave discharges was also found after FPL 12495 gavage and there was a
      prolongation of the mean duration. Behavioural changes were only noticed after
      the highest dose. These were accompanied by changes in the spectral content and
      particularly by an increase in the amplitude of the delta and the high beta
      frequencies, together with a decrease in the spindle frequency range. FPL 12495
      appeared to be more potent that remacemide in all its effects. The effects of
      mainly FPL 12495 are uncommon in the sense that so far no other investigated drug
      shows a decrease in the number together with an increase in the mean duration of
      the discharges. It seems that in contrast to other anti-epileptic drugs, FPL
      12495 exerts a differential action on the two commonly distinguished mechanisms
      controlling number and duration.

PMID- 7566471
TI  - Binding of the new radioligand (S)-[3H]AMPA to rat brain synaptic membranes:
      effects of a series of structural analogues of the non-NMDA receptor agonist
      willardiine.
AB  - This study examined the binding of (S)-[3H]AMPA, the radiolabelled active isomer
      of AMPA, to rat brain synaptic membranes. Under non-chaotropic conditions
      specific binding of 10 nM (S)-[3H]AMPA represented 33 +/- 2% of the total; this
      increased to 74 +/- 1% in the presence of 100 mM KSCN. (S)-[3H]AMPA binding was
      inhibited by non-NMDA receptor agonists and the antagonists NBQX and CNQX, with
      the following rank order of potency: NBQX > (S)-AMPA > or = quisqualate > CNQX >
      L-glutamate > domoate > or = kainate > (R)-AMPA. NMDA, and the metabotropic
      glutamate receptor agonist (1S,3R)-ACPD, up to 100 microM, did not inhibit (S)
      [3H]AMPA binding. A number of willardiine analogues all effectively inhibited (S)
      [3H]AMPA binding with the rank order of potency: (S)-5-fluorowillardiine > (S)-5
      nitrowillardiine > (S)-5-trifluoromethylwillardiine > (S)-5-bromowillardiine
      approximately (S)-5-chlorowillardiine > (S)-5-cyanowillardiine > (S)-willardiine
      > (S)-5-iodowillardiine > (S)-6-methylwillardiine > (S)-5-methylwillardiine. This
      rank order closely reflects data from equilibrium measurements made, under
      voltage clamp, on cultured hippocampal neurons. In contrast the respective (R)
      enantiomers and the racemate mixtures of (R,S)-3, 5 and 6-isowillardiine were
      relatively inactive. Similar IC50 values and thus rank orders of potency for the
      willardiines were observed in the presence of 100 mM KSCN.

PMID- 7566472
TI  - Influence of ketamine on the neuronal death caused by NMDA in the rat
      hippocampus.
AB  - The protection provided by ketamine against the neuronal cytotoxicity of NMDA was
      investigated and compared with that provided by dizocilpine (MK 801). A massive
      anaesthetic dose of ketamine (180 mg/kg) was required for substantial protection
      (about 70%) of rat dorsal hippocampal neurons. Protection was markedly decreased
      if the ketamine was given in three divided doses of 60 mg/kg over a period of 2
      hr, rather than as a bolus injection of 180 mg/kg. A lower dose (60 mg/kg i.p.)
      gave no protection when given 10 min prior to NMDA, but some protection (up to
      30%) was found when administration was delayed for 1-2 hr. After 3 hr, ketamine
      at this dose did not protect. In comparison, the toxicity of NMDA was reduced by
      about 70% by prior treatment with dizocilpine at 1 mg/kg, and completely
      eliminated at 10 mg/kg. The lack of protection when ketamine at 60 mg/kg was
      administered prior to NMDA may be due to a proconvulsant action of ketamine, as
      diazepam in the presence but not in the absence of ketamine significantly reduced
      the toxicity of NMDA. However, there was no behavioural or histological evidence
      of increased seizure activity in the presence of ketamine. Neuroprotectant
      effects may prevail with massive anaesthetic doses of ketamine or when diffusion
      has reduced the concentration of NMDA. The heroic doses of ketamine required for
      protection diminish its attractiveness as a potential anti-ischaemic agent.

PMID- 7566474
TI  - Effect of anticonvulsant drugs on peripheral benzodiazepine receptors of human
      lymphocytes.
AB  - Anticonvulsant drugs, such as carbamazepine, may exert some of their effects
      through peripheral benzodiazepine receptors (PBR), which are present in glial
      cells and regulate the synthesis of neurosteroids. PBR have also been
      demonstrated in human lymphocytes, where they might be used as peripheral markers
      of anticonvulsant drug effects. In the present paper we investigated the
      interaction of various antiepileptic drugs with PBR of human lymphocytes and
      evaluated possible effects of acute and chronic treatment with these drugs. At
      normal therapeutic concentrations, diazepam, carbamazepine and phenobarbital
      occupy respectively 70, 30 and 10% of PBR sites in human lymphocytes. Although no
      change of receptor density or affinity was observed after acute in vitro
      treatment, in epileptic patients chronically treated with carbamazepine,
      phenobarbital and valproic acid, PBR Bmax was increased with respect to controls
      and untreated epileptics. Since PBR of human lymphocytes may be affected by
      anticonvulsant drug treatment, we suggest that they might be involved in the
      immunological alterations reported in these patients and might be used as
      peripheral markers of drug effects on the central nervous system.

PMID- 7566475
TI  - Influence of BAY k-8644, a calcium channel agonist, on the anticonvulsant
      activity of conventional anti-epileptics against electroconvulsions in mice.
AB  - BAY k-8644, an agonist at the dihydropyridine binding site of the L-type voltage
      dependent calcium channel, at the dose of 5 mg/kg (s.c.) did not significantly
      affect the threshold for electroconvulsions, but impaired the protective efficacy
      of flunarizine (15 and 20 mg/kg, i.p.) in the electroconvulsive test.
      Interestingly, the calcium channel agonist (at 1 and 5 mg/kg) distinctly
      diminished the protection offered by conventional anti-epileptic drugs
      (carbamazepine, diphenylhydantoin and phenobarbital) against maximal electroshock
      induced seizures in mice. A pharmacokinetic interaction does not seem to be
      involved in the effect of BAY k-8644, since total plasma levels of these anti
      epileptics (measured by immunofluorescence) were not affected by the calcium
      channel agonist. The only anti-epileptic drug resistant to BAY k-8644 (up to 5
      mg/kg) was valproate, whose ED50 (in mg/kg) was not changed in the presence of
      the calcium channel agonist. Further, BAY k-8644 (5 mg/kg) did not influence the
      flunarizine (a calcium channel blocker)-induced potentiation of the protective
      action of valproate against maximal electroshock-induced convulsions. The calcium
      channel agonist (5 mg/kg) reversed the flunarizine-induced augmentation of the
      anticonvulsive activity of carbamazepine. It may be concluded that carbamazepine,
      diphenylhydantoin and phenobarbital partially exert their anticonvulsive effects
      via blockade of calcium influx whilst valproate does not seem to. In this
      context, the flunarizine-induced potentiation of the anticonvulsive activity of
      valproate is probably independent of calcium channel blockade.

PMID- 7566476
TI  - Induction of c-fos, jun B and egr-1 expression by haloperidol in PC12 cells:
      involvement of calcium.
AB  - Acute injection of haloperidol, a dopamine D2 receptor antagonist, is known to
      increase immediate early gene expression of the fos and jun families in rodent
      striatal neurons. A set of gene induction, including c-fos, jun B and TIS8/egr-1,
      was found when haloperidol was added to PC12 cells in culture. Electrophoretic
      mobility-shift assays show that haloperidol-evoked gene induction was accompanied
      by a transient and dose-dependent increase in AP1 and EGR-1 binding activities in
      these cells. Gene expression is tentatively explained by the rapid and transient
      increase in cytosolic free Ca2+ concentration observed upon haloperidol addition.
      The cytosolic calcium rise and AP1 binding activation elicited by haloperidol
      were dependent on extracellular Ca2+, suggesting that haloperidol exerted its
      effects by promoting Ca2+ entry into PC12 cells. The haloperidol-induced increase
      in AP1 binding activity and intracellular Ca2+ was not reproduced by two other
      dopamine D2 receptor antagonists, sulpiride and (+)-butaclamol.

PMID- 7566478
TI  - Effects of neurotensin in a rodent model of tardive dyskinesia.
AB  - The role of neurotensin (NT) in a putative model of tardive dyskinesia (TD) was
      examined in the rat. When administered directly into the ventrolateral striatum
      of neuroleptic-naive animals, NT (2.5 micrograms/side) elicited vacuous chewing
      movements. This response was not seen following administration of NT into other
      striatal regions or the substantia nigra and was suppressed by the NT antagonist
      SR 48692 (100 micrograms/kg i.p.). Vacuous chewing movements were also seen
      following chronic administration of fluphenazine decanoate. These movements were
      likewise suppressed by SR 48692 (10-100 micrograms/kg i.p.), which failed to
      affect other behavioural responses and was without effect in neuroleptic-naive
      animals. Our data suggest that increased levels of endogenous NT within the
      ventrolateral striatum may play a critical role in the development of TD
      following chronic neuroleptic administration and that NT antagonists may be
      beneficial for the treatment of this disorder.

PMID- 7566477
TI  - Effect of haloperidol and (-)-sulpiride on dopamine agonist-induced hypoactivity.
AB  - High doses of dopamine D2 receptor agonists produce hyperactivity in rodents
      whereas low doses suppress activity. In this study, low doses of a range of
      dopamine agonists were examined for their effects on locomotor activity in rats.
      All agonists caused a dose-related hypolocomotor effect with a rank order of
      potency of quinelorane > (-)-quinpirole > 7-OHDPAT > PBTO. (-)-Sulpiride (1.6-160
      mumol/kg), a neuroleptic with atypical properties caused a dose-related reversal
      of the hypolocomotor effect produced by all four agonists whereas the typical
      neuroleptic haloperidol (0.005-0.16 mumol/kg) did not reverse hypolocomotion.
      Neither sulpiride (5-16 mumol/kg) nor haloperidol (0.005-0.16 mumol/kg) affected
      locomotor activity per se, although haloperidol (1.6-5 mumol/kg) did reduce
      locomotor activity. The different behavioural profiles shown by (-)-sulpiride and
      haloperidol in these tests may reflect some of the clinical characteristics of
      these neuroleptics. The question of whether these effects can be ascribed to
      differential actions at dopamine receptor subtypes will only be answered when
      more selective dopamine receptor antagonists are developed.

PMID- 7566479
TI  - Opiate receptors.

PMID- 7566480
TI  - The dopaminergic system modulates the endogenous opioid system in guinea-pig
      isolated ileal longitudinal muscle.
AB  - The effects of the dopamine antagonists haloperidol and sultopride were
      investigated on the twitch response, evoked by 0.1 Hz stimulation of guinea-pig
      isolated ileal longitudinal muscle, and on the inhibition of the twitch response
      induced by 10 Hz stimulation (post-tetanic twitch inhibition) and by application
      of opioids. Both haloperidol and sultopride concentration-dependently inhibited
      the twitch response, with threshold concentrations of 2 and 50 microM,
      respectively, and could also shift the concentration-response curve for ACh
      contraction to the right in a non-competitive manner. Haloperidol (1 microM) and
      sultopride (20 microM) increased post-tetanic twitch inhibition and this could be
      prevented by naloxone (100 nM). Twitch inhibition induced by morphine and
      dynorphin 1-13 was not affected by haloperidol (1 microM) or sultopride (20
      microM). Prazosin (1 microM) and yohimbine (2 microM) did not affect either the
      twitch response or the post-tetanic twitch inhibition. These results suggest that
      dopamine receptors are involved in the modulation of the ileal opioid system, in
      such a manner as to diminish the release of endogenous opioids by tetanic
      stimulation.

PMID- 7566481
TI  - "Full" dopamine D1 agonists in human caudate: biochemical properties and
      therapeutic implications.
AB  - Recent data indicate that full D1 dopamine agonists have greater antiparkinsonian
      effects in the MPTP primate model than do partial agonists, suggesting that the
      intrinsic activity of D1 agonists may affect their utility in the treatment of
      Parkinson's disease. It is unclear, however, whether human D1 receptors in situ
      are similar to D1 receptors in other species or in molecular expression systems.
      For this reason, the binding affinity and functional activity of a series of D1
      dopamine receptor agonists [dihydrexidine (DHX), SKF82958, and A68930] were
      determined in postmortem human caudate. Results from in vitro binding studies
      with membranes from human caudate indicate that these D1 agonists competed for
      [3H]SCH23390 labeled sites with a rank order similar to that found in rat
      striatum [K50 = 36.8 nM (DHX); 18.6 nM (SKF82958); 3.9 nM (A68930)]. The ability
      of these compounds and the partial agonist SKF38393 to stimulate the enzyme
      adenylyl cyclase in tissue homogenates of human caudate was also examined. DHX
      and A68930 are full agonists compared to dopamine, whereas SKF82958 and SKF38393
      are partial agonists. These differences in biochemical intrinsic activity are
      consistent with the profound antiparkinsonian effects caused by DHX, but not by
      SKF82958 and SKF38393, in the MPTP-monkey model. This suggests that DHX and
      A68930 may be of greater utility in treating disorders where a full efficacy D1
      agonist may be required.

PMID- 7566483
TI  - Stimulation of median, but not dorsal, raphe 5-HT1A autoreceptors by the local
      application of 8-OH-DPAT reverses raclopride-induced catalepsy in the rat.
AB  - The local application of 8-OH-DPAT (0.5 or 2.5 micrograms/rat, 10 min) into the
      median, but not the dorsal, raphe nucleus resulted in a reversal of the catalepsy
      induced by the DA D2 receptor blocking agent raclopride (16 mg kg-1 s.c., 60
      min). The local application of 8-OH-DPAT into serotonergic projection areas of
      the forebrain (dorso-lateral neostriatum, accumbens core; 0.5 or 2.0
      micrograms/side) did not affect raclopride-induced catalepsy. Thus, the 5-HT1A
      autoreceptor in the median raphe nucleus is an important site of action for the
      reversal of DA D2 receptor antagonist-induced catalepsy by systemic
      administration of 5-HT1A receptor agonists, in the rat.

PMID- 7566484
TI  - Effects of single and repeated oral administration of fluvoxamine on
      extracellular serotonin in the median raphe nucleus and dorsal hippocampus of the
      rat.
AB  - The delay in clinical effects of selective serotonin reuptake inhibitors (SSRIs)
      suggest the existence of adaptive phenomena, such as receptor sensitivity
      changes. To examine the effects of repeated administration of SSRIs on serotonin
      neurotransmission, we investigated the effects of acute and chronic
      administration of the SSRI fluvoxamine on the extracellular levels of 5-HT in the
      median raphe nucleus and dorsal hippocampus of conscious rats by means of brain
      microdialysis. A single oral dose of fluvoxamine (30 mg/kg) augmented
      extracellular 5-HT in the median raphe and dorsal hippocampus to 270 and 191% of
      baseline level, respectively. Administration of fluvoxamine (30 mg/kg) or vehicle
      for 14 days did not affect 5-HT baseline levels. Moreover, the increase in
      extracellular 5-HT in the median raphe nucleus and dorsal hippocampus after an
      oral dose of fluvoxamine (30 mg/kg) in rats chronically treated with fluvoxamine
      was not different from rats treated with vehicle. Using RU 24969 as a probe for
      the sensitivity of the 5-HT1B autoreceptors in the dorsal hippocampus, no change
      in receptor sensitivity could be observed. These results demonstrate that
      repeated oral treatment with fluvoxamine does not affect extracellular 5-HT in
      the median raphe and dorsal hippocampus, suggesting that presynaptic functional
      changes of 5-HT in the brain areas tested are not implicated in the observed
      delayed onset of action of this SSRI in humans.

PMID- 7566482
TI  - Response of the damaged dopamine system to GM1 and semisynthetic gangliosides:
      effects of dose and extent of lesion.
AB  - GM1 ganglioside, administered to young C57/B16J mice with moderate (approx 85%) 1
      methyl-4-phenyl-1,2,3,6-terahydropyridine (MPTP)-induced striatal dopamine
      depletions, caused a dose-dependent increase in striatal dopamine levels. This
      effect was maximal between 7.0 and 30.0 mg/kg and was not apparent at higher and
      lower doses of GM1. GM1 ganglioside treatment had no effect on striatal dopamine
      levels in mice with more extensive lesions of the dopamine system (i.e. approx
      93% loss of striatal dopamine). The semisynthetic ganglioside derivative LIGA 20,
      administered orally, also increased striatal dopamine levels in moderately
      lesioned animals, albeit at lower doses than GM1. LIGA 20 administration also
      resulted in increased striatal dopamine levels in animals with more extensive
      dopamine lesions, where GM1 had no effect. These results show that both GM1 and
      its semisynthetic derivative LIGA 20 can partially restore striatal dopamine
      levels in MPTP-treated mice and that LIGA 20 is more potent and not subject to
      the same dose-limiting effects as GM1.

PMID- 7566485
TI  - Hypotension induces Fos immunoreactivity in NADPH-diaphorase positive neurons in
      the paraventricular and supraoptic hypothalamic nuclei of the rat.
AB  - Double staining for Fos and nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-D) was used to study the distribution of activated neurons that
      synthesize nitric oxide in the paraventricular (PVN) and supraoptic nuclei (SON)
      following hypotensive stimulation in conscious rats. Fos was detected in many
      magno- and parvocellular NADPH-D positive neurons in response to haemorrhage or
      drug-evoked hypotension using i.v. infusions of sodium nitroprusside. However,
      quantitative analysis did not reveal any differences in the number of Fos
      positive PVN neurons following either mode of stimulation. These results suggest
      that a subpopulation of hypothalamic NADPH-D positive neurons is activated
      following hypotensive challenge. This activation of NADPH-D neurons may occur
      indirectly through other CNS structures that influence the excitability of
      hypothalamic SON and PVN. Furthermore, the lack of a difference in activated
      neurons within the PVN following either haemorrhage or nitroprusside infusion
      suggests that while a drop in blood pressure causes activation of neurons that
      produce nitric oxide, a decrease in blood volume, which accompanies haemorrhage,
      does not.

PMID- 7566486
TI  - Stimulation of zif/268 gene expression by basic fibroblast growth factor in
      primary rat striatal cultures.
AB  - The presence of basic fibroblast growth factor (bFGF) in the basal ganglia, and
      its known neurotrophic activity, has created interest in its possible role as an
      agent to attenuate striatal neurodegeneration. However, little information is
      available on the mechanisms through which bFGF might exert a long-term influence
      on striatal function. Primary cultures of embryonic rat striatal neurones were
      used to ascertain whether bFGF can alter the pattern of striatal gene expression.
      Treatment of cultures with bFGF (500 pM) resulted in a dramatic increase in the
      levels of zif/268 mRNA within 45 min. This induction was attenuated by the
      tyrosine kinase inhibitor genistein (100 microM), but not by its inactive
      structural analogue genistin (100 microM). The induction of zif/268 mRNA was
      found to occur in non-neuronal cells, with no increase in mRNA levels being
      observed in neurones. A similar induction was noted for another putative
      transcription factor, jun B, although no induction of the related factor jun D
      could be detected. These results show that bFGF can induce immediate-early gene
      expression in striatal cultures, and therefore that this may provide a mechanism,
      mediated by non-neuronal cells, which allows bFGF to cause a long-term change in
      striatal neurochemistry.

PMID- 7566487
TI  - Differential temporal patterns of expression of immediate early genes in cerebral
      cortex induced by intracerebral excitotoxin injection: sensitivity to
      dexamethasone and MK-801.
AB  - A number of conditions associated with persistent excitation such as electrically
      and chemically-induced seizures cause a rapid increase in the expression of
      immediate early genes (IEG) such as c-fos. In this study the time-course of
      induction of c-jun, jun-B and zif 268 mRNA by kainate was characterized in rat
      cerebral cortex and compared to that of c-fos mRNA induction. Unilateral
      injection of kainate into the nucleus basalis caused a significant induction of c
      jun mRNA in cerebral cortex from 4 hr which was maximal at 8 hr, being 3 times
      greater in ipsilateral cortex than in control cortex. This pattern was also shown
      for jun-B and was similar, but of small magnitude, to that obtained with c-fos
      mRNA, with a maximal increase at 8 hr, whilst the maximal induction of zif-268
      mRNA preceded these responses occurring at 4 hr. A marked difference was seen in
      duration in the c-jun induction which was maintained at a high level for at least
      24 hr. Treatment of animals with MK-801 (within 30 min of injection of kainate)
      or dexamethasone (2-30 mg/kg) at the time of kainate injection significantly
      attenuated the response. The induction of c-fos mRNA by kainate injection was
      most sensitive to dexamethasone (2 mg/kg), whereas a higher dose (30 mg/kg) was
      required to attenuate the induction of zif-268 mRNA. These results show that a
      time-dependent and co-ordinated induction of c-fos, c-jun, jun-B and zif-268 mRNA
      in cerebral cortex occurs in response to the persistent excitation caused by
      excitotoxin injection which is mediated by glutamate and shows a differential
      sensitivity to dexamethasone.

PMID- 7566488
TI  - Different binding affinities of NMDA receptor channel blockers in various brain
      regions--indication of NMDA receptor heterogeneity.
AB  - The N-methyl-D-aspartate (NMDA) receptor-channel complex exists in multiple forms
      which probably have different physiological and pharmacological properties. To
      further evaluate this concept of different NMDA receptor subtypes, receptor
      binding and autoradiographic techniques were used to study the phencyclidine
      (PCP) binding site of the NMDA receptor ion-channel complex. [3H]MK-801 was
      employed to characterize binding properties of (+)-MK-801, (-)-MK-801,
      phencyclidine (PCP), (+/-)-ketamine, amantadine (1-amino-adamantane) and
      memantine (3,5-dimethyl-1-amino-adamantane) in different brain regions.
      Saturation experiments on homogenized membranes revealed the existence of single
      classes of binding sites in cortex and cerebellum but with significant different
      affinities between these regions (KD/Cortex = 4.59 nM, Bmax/Cortex = 0.836
      pmol/mg protein; KD/Cereb. = 25.99 nM, Bmax/Cereb. = 0.573 pmol/mg protein)
      suggesting that the lower affinity in cerebellum indicates another population of
      NMDA receptor channels. In contrast, in striatum there was clear evidence for two
      binding sites (KD/high = 1.43 nM, Bmax/high = 0.272 pmol/mg protein; KD/low =
      12.15 nM, Bmax/low = 1.76 pmol/mg protein). Displacement studies (autoradiography
      and binding) revealed a lower affinity for unlabeled (+)-MK-801 in striatum which
      was clearly not the case for memantine. In cerebellar membranes there was a
      significant decrease in the affinity for both MK-801 enantiomers and PCP but not
      for the 1-amino-adamantanes. In contrast, all compounds showed lowered affinity
      in the dentate gyrus. These findings support NMDA receptor heterogeneity which
      may be of particular relevance for the development of subtype-selective drugs.

PMID- 7566490
TI  - Phenytoin delays ischemic depolarization, but cannot block its long-term
      consequences, in the rat hippocampal slice.
AB  - The anticonvulsant phenytoin has been reported to block anoxia-induced losses of
      synaptic activity in the rat hippocampal slice and experimental ischemia-induced
      losses of synaptic activity in the guinea pig hippocampal slice. We examined
      phenytoin in our rat hippocampal slice model of experimental ischemia (anoxia +2
      mM D-glucose). In this model, ischemic depolarization (ID) occurs 4-5 min after
      the introduction of anoxic medium, and oxygen and D-glucose are restored 1 min
      after the onset of ID. In control slices, synaptic recovery is never observed
      following ID in 2 mM D-glucose. Phenytoin (30,100 and 300 microM), perfused for
      20 min prior to, and for 10 min following anoxia, did not allow for synaptic
      recovery following ID. At the higher concentrations, however, it did increase the
      latency to ID. In addition, the presynaptic volley (PV), which normally
      disappears at the time of ID, was lost substantially earlier in the presence of
      phenytoin. These findings suggest that the anti-ischemic effects of phenytoin
      reported by others are due to delay of ID. This may suggest that phenytoin will
      be effective in preventing global ischemia-induced damage only when the ischemic
      insult is of short duration.

PMID- 7566489
TI  - The effects of four general anesthetics on intracellular [Ca2+] in cultured rat
      hippocampal neurons.
AB  - It has been suggested that general anesthesia might arise as a consequence of
      increased cytoplasmic free ionized calcium concentration ([Ca2+]i). The effect of
      increased [Ca2+]i might be to activate K+ channels or to modulate other ion
      channels important for the control of excitability, such as the GABAA receptor. A
      direct test of this hypothesis has not been reported. Microfluorimetry with the
      calcium-sensitive dye fura-2 was used to study the effects of four anesthetic
      agents on the regulation of intracellular free Ca2+ in hippocampal neurons
      cultured from the embryonic rat hippocampus. Basal intracellular free ionized
      calcium concentration [Ca2+]i in the neurons was 50-100 nM. Depolarization of the
      neurons with 50 mM K+ resulted in the elevation of [Ca2+]i to 200-800 nM, with
      subsequent recovery of [Ca2+]i over several minutes. The volatile anesthetics
      halothane, enflurane and isoflurane did not alter basal [Ca2+]i, even above
      clinically relevant concentrations; however, they did inhibit elevation of
      [Ca2+]i by high K+ stimulation. The intravenous anesthetic methohexital caused
      small increases in basal [Ca2+]i at concentrations > or = 50 microM; methohexital
      (5-50 microM) also inhibited elevations of [Ca2+]i induced by high K+. The
      evidence presented here suggests that the anesthetics studied do not produce
      their actions via sustained or transient increases in [Ca2+]i. However, all of
      the anesthetics studied appear to possess inhibitory effects on hippocampal
      voltage-dependent Ca2+ channels, in addition to their previously described
      effects at GABAA receptors.

PMID- 7566491
TI  - Block of spatial learning by mGluR agonist tADA in rats.
AB  - As demonstrated recently, mGluRs are involved in some forms of learning. We thus
      investigated the effect of tADA (trans-azetidine-2,4-dicarboxylic acid) applied
      intracerebroventricularly prior to learning a spatial alternation paradigm.
      Compared to controls, tADA treated animals were amnesic when tested for retention
      24 hr after training. Effects of state-dependency were excluded. These data and
      our earlier work indicate that both mGluR agonists and antagonists can have
      memory-disrupting effects.

PMID- 7566492
TI  - Neuronal nicotinic receptors: molecular organization and regulations.

PMID- 7566493
TI  - Human alpha 7 nicotinic acetylcholine receptor responses to novel ligands.
AB  - Responses of the human alpha 7 nicotinic acetylcholine receptor (nAChR) in
      Xenopus laevis oocytes were quantified using two-electrode voltage clamp in the
      presence of barium (10 mM) to block secondary activation of Ca(2+)-dependent
      chloride currents. The effect of (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)
      isoxazole (ABT-418) and (2,4)-dimethoxybenzylidene anabaseine (GTS-21), two
      potential compounds for the treatment of Alzheimer's Disease, and of the natural
      product (+/-)epibatidine were compared to (-)nicotine. (+/-)Epibatidine acted as
      an agonist and was 64-fold more potent than (-) nicotine (EC50s = 1.30 +/- 0.11
      microM and 83 +/- 10 microM, respectively). ABT-418 also was an agonist, 3-fold
      less potent and 75% as efficacious as (-)nicotine (EC50 = 264 +/- 34 microM). GTS
      21, in contrast, inhibited the response to (-)nicotine at concentrations < or =
      10 microM and itself elicited only a small response at higher concentrations (12%
      of the (-)nicotine response at 1 mM). Reversible blockade by methyllycaconitine
      (10 nM) corroborated the responses as due to activation of alpha 7 nAChR. This
      represents the first characterization of human alpha 7 nAChR responses to these
      novel nicotinic agonists.

PMID- 7566494
TI  - Actions of nitromethylenes on an alpha-bungarotoxin-sensitive neuronal nicotinic
      acetylcholine receptor.
AB  - Nine nitromethylene analogues were tested for their actions on insect neuronal
      nicotinic acetylcholine receptors (nAChRs). Microelectrode recordings were used
      to study the actions of nitromethylenes on the cell body of an identified
      cockroach (Periplaneta americana) motor neurone, the fast coxal depressor (Df) in
      the metathoracic ganglion. Six nitromethylenes showed potent nAChR agonist
      actions; others were without nAChR agonist actions. Five nitromethylenes
      competitively displaced bound [125I]-alpha-bungarotoxin from cockroach nervous
      system membranes. The rank orders of potency for the compounds determined by
      their depolarizing actions and their ability to displace [125I]-alpha
      bungarotoxin binding were similar. These findings, together with toxicity data
      obtained on the insects, Nephotettix cinciteps and Nilaparvata lugens, support
      the hypothesis that insect nAChRs are molecular targets of nitromethylene
      insecticides. Structure-activity relationships of the nitromethylenes suggest
      that optimal activity at neuronal nAChRs requires the presence of an electron
      withdrawing component in the region of the aryl substituent and an electron
      donating component at the 3' position of the imidazolidine ring.

PMID- 7566496
TI  - Idazoxan-induced reductions in cortical glucose use are accompanied by an
      increase in noradrenaline release: complementary [14C]2-deoxyglucose and
      microdialysis studies.
AB  - The autoradiographic [14C]2-deoxyglucose procedure was used to map function
      related alterations in local cerebral glucose use following acute administration
      of the alpha 2-adrenoceptor antagonist, idazoxan (0.3-3 mg kg-1 s.c.). The most
      prominent feature of the results obtained was the significant reduction in
      glucose use in certain locus coeruleus projection areas. Thus, in various
      cortical, hippocampal and thalamic regions, as well as structures involved in
      auditory and visual function, idazoxan administration was associated with a 13
      20% decrease in glucose use. In a complementary microdialysis study, the effect
      of idazoxan on extracellular noradrenaline levels in the frontal cortex of rats,
      manipulated in the same fashion as during the [14C]2-deoxyglucose procedure (i.e.
      following the application of surgery and partial restraint), was examined. Both
      surgery and restraint were associated with a modest but significant increase in
      basal noradrenaline release (+31% and +26%, respectively). Subsequent
      administration of idazoxan (3 mg kg-1 s.c.) evoked a further increase in
      noradrenaline release, the magnitude of which was the same as that observed
      following its administration to freely-moving rats (+113%). These combined data
      suggest that idazoxan-induced reductions in cerebral glucose use, at least in the
      frontal cortex, may occur as a consequence of the increase in noradrenaline
      release. In addition, it appears that surgery and partial restraint do not alter
      alpha 2-adrenoceptor tone in the frontal cortex.

PMID- 7566495
TI  - Differential effects of calcium channel antagonists on tityustoxin and ouabain
      induced release of [3H]acetylcholine from brain cortical slices.
AB  - In this paper, the effect of calcium channel blockers on acetylcholine release
      induced by tityustoxin and ouabain in rat brain cortical slices is described.
      Cadmium, a non-specific blocker of calcium channels, inhibited the release of ACh
      induced by tityustoxin. L-type calcium channel blockers (verapamil, nifedipine
      and diltiazen) had no effect on the release of ACh induced by tityustoxin. The
      release of ACh was also unaffected by nickel, a T-type calcium channel blocker,
      and the conotoxins GVIA and MVIIC, blockers of N and Q-type calcium channels.
      Agatoxin IVA, a specific blocker of the P-type calcium channel, inhibited the
      release of ACh induced by tityustoxin by 50%. The spontaneous release of ACh as
      well as ouabain-induced release of ACh was unaffected by any of the calcium
      channel blockers studied. It is concluded that ACh release induced by tityustoxin
      is mediated by Ca2+ influx via P-type calcium channels.

PMID- 7566497
TI  - Studies on the role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the
      inhibition of 5-HT release--I. BMY7378 and prazosin.
AB  - The present study utilized in vivo microdialysis to investigate the importance of
      5-HT1A autoreceptors and alpha 1-adrenoceptors in the decreased 5-HT release
      obtained following administration of the mixed 5-HT1A autoreceptor partial
      agonist/alpha 1-adrenoceptor antagonist BMY7378, the selective 5-HT1A receptor
      agonist 8-OH-DPAT and the alpha 1-adrenoceptor antagonist prazosin. BMY7378 (0.25
      mg/kg, s.c.), 8-OH-DPAT (0.025 mg/kg, s.c.) and prazosin (0.1-1.0 mg/kg, s.c.)
      all suppressed ventral hippocampal 5-HT efflux. The BMY7378- and 8-OH-DPAT
      induced inhibition of 5-HT release were reversed by a 40 min pre-treatment with
      either (+/-)pindolol (8 mg/kg, s.c.) or WAY-100635 (0.3 mg/kg, s.c.), to block 5
      HT1A autoreceptors. Neitehr of these antagonists altered the prazosin-induced
      (0.3 mg/kg, s.c.) 5-HT disease. THE RESULTS: (i) confirm that both an alpha 1
      adrenoceptor antagonist (prazosin) and 5-HT1A autoreceptor stimulants (BMY7378
      and 8-OH-DPAT) may reduce cerebral 5-HT release; (ii) support that the BMY7378
      induced decrease in 5-HT release results from 5-HT1A autoreceptor agonism, rather
      than alpha 1-adrenoceptor blockade; and (iii) argue against "physiological"
      antagonism (i.e. via blockade of beta-adrenoceptors, 5-HT1B receptors or some
      other mechanism) as an explanation for the reversal by pindolol of 5-HT1A
      autoreceptor agonist-induced suppression of 5-HT release. These data support the
      usefulness of pindolol, as well as the more specific compound WAY-100635, to
      block 5-HT1A autoreceptors.

PMID- 7566498
TI  - Ifenprodil inhibition of the 5-hydroxytryptamine3 receptor.
AB  - The anti-hypertensive drug ifenprodil is known to interact potently with the
      alpha 1-adrenergic receptor as well as a number of other second messenger-linked
      receptors. In addition to these properties, ifenprodil has been shown to prevent
      glutamate-mediated excitotoxicity via non-competitive antagonism of NMDA
      receptors [Legendre and Westbrook (1991) Molec. Pharmac. 40: 289-298; Shalaby et
      al. (1992) J. Pharmac. Exp. Ther. 260: 925-932]. With these things in mind, we
      have begun to examine the specificity of ifenprodil for various ligand-gated ion
      channels using electrophysiological methods. While ifenprodil effectively
      inhibits NMDA-mediated currents in cortical neurons in culture, it does not
      interact with either kainate or GABA receptors. Surprisingly, ifenprodil also
      acts as a relatively potent antagonist of the 5-hydroxytryptamine3 (5-HT3)
      receptor in the NG108-15 neuroblastoma x glioma cell line. Furthermore, several
      aspects of ifenprodil action on the 5-HT3 receptor resemble its interaction with
      the NMDA receptor. Namely, inhibition of 5-HT3-mediated cation currents is
      readily reversible, has relatively slow onset, is non-competitive, and is not
      voltage dependent. Since most of the known 5-HT3 antagonists are competitive, it
      is possible that ifenprodil may define a unique modulatory site(s) on this
      neurotransmitter receptor.

PMID- 7566500
TI  - Substantial regional and hemispheric differences in brain nitric oxide synthase
      (NOS) inhibition following intracerebroventricular administration of N omega
      nitro-L-arginine (L-NA) and its methyl ester (L-NAME).
AB  - Nitric oxide synthase (NOS) enzyme activity was determined in a comprehensive
      selection of regions of the rat brain. The effects of lateral ventricular
      administration of N omega-nitro-L-arginine (L-NA, 30 micrograms) and its methyl
      ester (L-NAME, 3-100 micrograms) on NOS activity were examined in the ipsilateral
      and contralateral areas of 4 of these brain regions and in the cerebellum. NOS
      activity was determined using a new and rapid ex vivo assay method which ensures
      minimal dissociation of the enzyme-inhibitor complex. Following infusion of L
      NAME, NOS activity was rapidly and dose-dependently inhibited in all brain
      regions studied (cerebral cortex, striatum, hippocampus, cerebellum and
      thalamus). However, NOS activity of brain regions within the contralateral
      hemisphere was inhibited significantly less than in ipsilateral regions, with the
      exception of the thalamus. The degree of NOS inhibition varied markedly between
      brain regions within each hemisphere and correlated with their ventricular
      proximity to the site of NOS inhibitor administration. Therefore, NOS in the
      thalamus was inhibited most effectively and NOS in the cerebral cortex the least.
      Within the cerebral cortex further regional differences could be observed, with
      NOS in the frontal/parietal areas inhibited more effectively than NOS in the
      temporal/occipital areas. Maximal inhibition of NOS was sustained for approx 6 hr
      after administration of 30 and 100 micrograms L-NAME. No inhibition of NOS was
      observed 24 hr after administration. Lateral ventricular administration of the
      metabolite and active moiety of L-NAME, L-NA, resulted in a similar degree of
      inhibition and time of inhibitory onset. In contrast, when L-NAME was
      administered i.p., a significant delay in the onset of NOS inhibition was
      observed in the above brain regions compared to L-NA. However, no regional or
      hemispheric differences in NOS inhibition were detected following peripheral
      administration of these inhibitors. These results indicate that central
      administration of NOS inhibitors yields a complex pattern of NOS inhibition and
      that data obtained on brain physiology following the i.c.v. administration of NOS
      inhibitors, or for that matter any other CNS effector, should therefore be
      interpreted with extreme caution.

PMID- 7566499
TI  - Comparative study of the affinities of the 5-HT3 receptor antagonists, YM060,
      YM114 (KAE-393), granisetron and ondansetron in rat vagus nerve and cerebral
      cortex.
AB  - The 5-HT3 receptor blocking properties of YM060, YM114 (KAE-393), granisetron and
      ondansetron were examined in the vagus nerve and cerebral cortex of rats. 5-HT
      and 2-methyl-5-HT induced dose-dependent depolarizations of rat isolated vagus
      nerve with EC50 values of 2.53 (1.93-3.33) x 10(-6) and 4.03 (2.87-5.66) x 10(-6)
      M, respectively. YM060, YM114 and granisetron dose-dependently antagonized the
      depolarization of the rat vagus nerve induced by 5-HT, with decreases in the
      slope and maximal response at higher concentrations. Apparent pA2 values for
      these antagonists were 10.27 +/- 0.09, 10.12 +/- 0.16 and 9.44 +/- 0.40,
      respectively. Ondansetron produced a clear rightward shift of the concentration
      response curve to 5-HT. The pA2 value was 8.63 (8.23-9.68). YM060 and YM114 at up
      to 10(-5) M produced no significant depression of the depolarizing responses to
      DMPP and GABA. YM060, YM114, granisetron and ondansetron displaced specific
      binding of [3H]GR65630 to rat cortical membranes with pKi values of 10.48 (10.41
      10.57), 10.24 (10.18-10.28), 9.15 (9.02-9.28) and 8.70 (8.64-8.77), respectively.
      An excellent correlation (r = 0.97) was obtained between pA2 values in the vagus
      nerve and pKi values in the cerebral cortex. YM060, YM114, granisetron and
      ondansetron showed low affinities for 5-HT1A, 5-HT2 receptor, adrenergic alpha 1,
      alpha 2, dopamine D2, muscarinic M2, mu-opioid, benzodiazepine and histamine H1
      receptors. These results support the possibility that the same type of 5-HT3
      receptor occurs in rat vagus nerve and cerebral cortex.

PMID- 7566501
TI  - The neurotoxin, beta-N-methylamino-L-alanine (BMAA) interacts with the strychnine
      insensitive glycine modulatory site of the N-methyl-D-aspartate receptor.
AB  - Electrophysiological and receptor binding techniques were used to determine
      whether the neurotoxin beta-N-methylamino-L-alanine (BMAA), a monocarboxylic
      amino acid, can act at the strychnine-insensitive glycine modulatory site to
      modify the activity of N-methyl-D-aspartate receptors. DL-BMAA but not L-BMAA
      reversibly potentiated the amplitude of NMDA-activated currents. Neither DL-BMAA
      nor L-BMAA were able independently to active currents. The reversal potential and
      the potential-dependence of the amplitude were not affected by DL-BMAA. The DL
      BMAA effect was reversibly antagonized by 7-chlorokynurenic acid. Concentration
      jump experiments showed that the time course of the "off" response of NMDA
      activated currents in the presence of DL-BMAA is faster than in the presence of
      glycine, suggesting that DL-BMAA dissociates from the receptor more rapidly than
      glycine. DL-BMAA produced a concentration-dependent displacement of [3H]glycine
      binding which was additive with that of 7-chlorokynurenic acid. These data
      indicate that D-BMAA could act as a stereospecific modulator of NMDA receptor
      function by acting as an agonist at the strychnine-insensitive glycine modulatory
      site of the NMDA receptor.

PMID- 7566502
TI  - Interactions between NMDA and AMPA glutamate receptor antagonists during
      halothane anesthesia in the rat.
AB  - There is increasing evidence that pharmacologic antagonism of glutamatergic
      neurotransmission can potentiate the anesthetic effects of drugs such as
      halothane. The purpose of this study was to examine the anesthetic interaction
      between glutamate receptor antagonists. A competitive NMDA receptor antagonist
      (CGS 19755) and an AMPA receptor antagonist (NBQX) were administered either alone
      or in combination prior to determination of the minimum alveolar concentration
      (MAC) for halothane in the rat. CGS 19755 caused a dose-dependent maximum
      reduction in halothane MAC of approximately 80%. Doses of NBQX, which were low
      enough to cause no change in MAC when administered alone, substantially reduced
      MAC when administered with subanesthetic doses of CGS 19755. This effect
      decreased as the dose of CGS 19755 was increased. Finally, halothane MAC was
      reduced to zero when NBQX, in a dose sufficient to reduce halothane MAC by
      approximately 35% if given alone, was added to a pharmacodynamically similar dose
      of CGS 19755. Although MAC is believed to predominantly reflect nocioception at
      the spinal cord level, the results suggests that pharmacologic blockade of
      glutamatergic neurotransmission is sufficient to result in deep levels of
      anesthesia. Further, the effect of combinations of NMDA and AMPA receptor
      antagonists on halothane MAC is consistent with an in vivo physiologic
      interaction between the NMDA and AMPA receptors.

PMID- 7566503
TI  - Anandamide decreases naloxone-precipitated withdrawal signs in mice chronically
      treated with morphine.
AB  - The effect of anandamide, a putative endogenous ligand of the cannabinoid
      receptor, has been studied in a naloxone-precipitated morphine withdrawal
      syndrome in mice. Animals were chronically treated with increasing doses of
      morphine (from 8 to 45 mg/kg) over 5 days or implanted with morphine pellets (72
      hr). Typical signs of withdrawal (jumping and body weight loss) were examined
      after naloxone administration (1 mg/kg). In these conditions, anandamide (5
      mg/kg, i.v.) decreased both the number of jumps, measured over 30 min (81.2% +/-
      3.15 and 92.2% +/- 3.5 decrease in chronically administered morphine and pellet
      implanted mice, respectively), and the body weight loss at 30 and 60 min (30 min:
      2.6% +/- 0.4 vs 4.4% +/- 0.2 and 3.7% +/- 0.4 vs 5.3% +/- 0.4; 60 min: 3.2% +/-
      0.5 vs 5.0% +/- 0.4 and 4.1% +/- 0.5 vs 6.0% +/- 0.5 in chronically treated
      morphine and pellet implanted mice respectively) after naloxone administration.
      This suggests, as shown in the case of delta 9-tetrahydrocannabinol, a modulation
      by anandamide of pathways involved in the expression of physical signs of opioid
      dependence and support its role as an endogenous cannabinoid agonist.

PMID- 7566504
TI  - Discriminative stimulus effects of CP 55,940 and structurally dissimilar
      cannabinoids in rats.
AB  - CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in
      a number of studies as a radioligand for the cannabinoid receptor. This compound
      shares behavioral and biochemical properties with naturally occurring
      cannabinoids such as delta 9-THC. The purpose of the present study was 3-fold: to
      establish the ability of CP 55,940 to serve as a discriminative stimulus, to
      determine whether this discriminative stimulus is identical to that of delta 9
      THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A,
      would antagonize the discriminative stimulus effects of CP 55,940. Rats were
      trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever
      operant conditioning chambers. CP 55,940 produced dose-dependent generalization
      from the training dose in dose-effect determinations conducted before and after
      testing with other drugs. The effects of the training dose of CP 55,940 were dose
      dependently antagonized by co-administration of SR141716A. Results of
      substitution tests showed that delta 9-THC, WIN 55,212-2, and cannabinol
      substituted completely for CP 55,940 in a dose-dependent manner; however, CP
      55,940 was approx 10-fold more potent than any of the other drugs in producing CP
      55,940-like discriminative stimulus effects. Several drugs with CNS depressant
      properties (phencyclidine, haloperidol and diazepam) failed to produce reliable
      substitution for CP 55,940. These results demonstrate that CP 55,940 has
      discriminative stimulus effects and that it shares these effects with
      structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid
      receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor
      antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566505
TI  - Effects of SCH 32615, an enkephalinase inhibitor, on D-1 and D-2 dopamine
      receptor-mediated behaviors.
AB  - Striatal enkephalin-containing neurons receive dopaminergic inputs from the
      substantia nigra and project to the external segment of globus pallidus. These
      neurons express primarily dopamine (DA) D-2 receptors. Accordingly, stimulation
      of enkephalinergic transmission might be expected to influence mainly D-2
      receptor agonist or antagonist effects on motor function. To test this
      hypothesis, the effects of SCH 32615, an enkephalinase inhibitor, on DA
      antagonist-induced catalepsy, DA D-1 agonist-induced non-stereotyped grooming,
      and DA D-2 agonist-induced stereotyped behavior were studied. The administration
      of SCH 32615 (3 mg/kg) decreased both D-1 and D-2 antagonist-induced catalepsy.
      In contrast, SCH 32615 (0.3 mg/kg) increased D-1 agonist-induced non-stereotyped
      grooming and D-2 agonist-induced stereotypies. These results suggest that a DA
      agonist-like, mostly D-2 activity may be involved in enkephalinergic-mediated
      functions.

PMID- 7566506
TI  - Current bibliographies of neuropeptides prepared by The University of Sheffield
      Biomedical Information Service.

PMID- 7566507
TI  - Nitrinergic and peptidergic innervations and their inter-relationships in human
      colon.
AB  - The distribution and colocalization of nitrinergic and peptidergic nerves were
      examined in six human colons. The tissues were fixed, cryosectioned, and standard
      immunohistochemistry was performed for several known neuropeptides. The same
      sections were stained for NADPH-diaphorase to denote nitric oxide synthase. NADPH
      diaphorase-positive myenteric neurons were counted and colocalization noted for
      each peptide, as well as for peptide terminations. Galanin was the only
      neuropeptide that colocalized to a significant extent (23.0 +/- 7.21%) with NADPH
      diaphorase-positive myenteric neurons. Many neuropeptide-containing nerve fibers
      had extensive terminations onto NADPH-diaphorase-positive neurons. Vasoactive
      intestinal peptide was the only neuropeptide that colocalized with NADPH
      diaphorase to any extent in nerve fibers within circular muscle (59.5 +/- 9.3%).
      Fiber distribution in the longitudinal muscles showed a similar, but less dense
      pattern. These observations provide morphological evidence for the presence of
      nitric oxide, a candidate nonadrenergic noncholinergic neurotransmitter in the
      human colon.

PMID- 7566509
TI  - Involvement of serotonin in the regulation of GnRH gene expression in the male
      rat brain.
AB  - The role of serotonin (5-HT) in the regulation of the hypothalamo-pituitary
      gonadal axis is still controversial. In order to evaluate the influence of 5-HT
      on gonadotropin-releasing hormone (GnRH) neurons, we have investigated the
      effects of repeated administration (during 2 days) of 5-HT, the 5-HT1+2 receptor
      antagonist methysergide, the 5-HT2 receptor antagonist ketanserin, and the 5-HT3
      receptor antagonist ondansetron on GnRH mRNA levels in the male rat medial
      preoptic area (MPOA), as measured by quantitative in situ hybridization. The
      treatment with 5-HT decreased by 32% the number of silver grains overlying
      labelled neurons. The administration of methysergide and ketanserin increased the
      hybridization signal by 32% and 29%, respectively. On the other hand, the 5-HT3
      receptor antagonist did not modify GnRH mRNA levels. The present results clearly
      indicate that the serotoninergic system exerts a negative tonic influence on the
      biosynthesis of GnRH as evaluated by mRNA level measurements. They also strongly
      suggest that the influence of 5-HT in the regulation of GnRH neuronal activity is
      mediated via activation of 5-HT2 receptor, although an involvement of 5-HT1
      receptors cannot be totally excluded.

PMID- 7566510
TI  - SR 48692-sensitive neurotensin receptors modulate acetylcholine release in the
      rat striatum.
AB  - The effects of stimulation and blockade of neurotensin receptors on striatal
      acetylcholine release were examined in anaesthetized rats using microdialysis.
      Local perfusion with neurotensin (100 nM) did not influence the release of
      acetylcholine. Application of neurotensin (100 nM) 30 min after haloperidol (125
      micrograms/kg, i.p.) increased acetylcholine levels to 188% compared to 120% when
      haloperidol was administered alone. SR 48692 (3-100 micrograms/kg, i.p.) dose
      dependently reduced the stimulatory effect of neurotensin in the presence of
      haloperidol. Comparable antagonism was observed with SR 48527, a chemically
      related compound with high affinity for neurotensin receptors, but not with SR
      49711, its low-affinity antipode. These results indicate that high affinity
      neurotensin receptors regulate acetylcholine release, when D2-dopaminergic
      inhibitory input is suppressed.

PMID- 7566511
TI  - Neuropeptide Y- and vasoactive intestinal polypeptide-like immunoreactivity in
      adjuvant arthritis: effects of capsaicin treatment.
AB  - The occurrence of the neuropeptides vasoactive intestinal polypeptide (VIP) and
      neuropeptide Y (NPY) in ankle joints and dorsal root ganglia (L2-L6) was analyzed
      in normal and arthritic Lewis rats. In addition the effect of capsaicin
      pretreatment was investigated. The study included 92 rats consisting of 4 groups,
      23 rats in each; normal rats, normal rats given capsaicin, arthritic rats and
      arthritic rats pretreated with capsaicin. The localization of the neuropeptides
      was assessed by immunohistochemistry and the tissue concentrations were
      determined by radioimmunoassay (RIA). In the arthritic rats, there was a slight
      increase in NPY immunoreactive nerve fibres in the ankle joint synovium and bone
      marrow, as compared to normal rats. Notably, there was an intense fluorescence
      and significant increase (p < 0.01, 41%) in the number of NPY-positive
      megakaryocytes in the tibial bone marrow of arthritic rats. RIA showed that the
      concentration of NPY-like immunoreactivity (LI) was increased by 50% in the ankle
      joint. Pretreatment with capsaicin did not affect the increased level of NPY-LI
      in the ankle joint of arthritic rats. The concentration of NPY-LI in the dorsal
      root ganglia was not altered in arthritic rats, nor was it affected by the
      capsaicin treatment. No NPY immunoreactive cells could be detected in the dorsal
      root ganglia. The number of VIP immunoreactive nerve fibres observed in ankle
      joints of arthritic and normal rats did not differ. However, RIA measurements
      showed an 11% increase in the VIP concentration in arthritic rats, which was
      unaffected by capsaicin treatment. In dorsal root ganglia, RIA disclosed a 21%
      increase in VIP-LI, although no VIP-positive cells could be detected. Capsaicin
      treatment did not affect the increased concentration of VIP-LI in the dorsal root
      ganglia.

PMID- 7566508
TI  - Effects of mu opioid agonist and antagonist on neurological outcome following
      traumatic brain injury in the rat.
AB  - We examined the effects of an exogenous mu opioid agonist and antagonist on
      systemic physiology and neurological outcome following TBI in the rat. Experiment
      I: [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) (0.1 nMol or 0.3 nMol in 5
      microliters) (n = 10) or artificial CSF (n = 10) was administered 5 min prior to
      fluid-percussion brain injury (2.1 atmospheres). Motor performance was assessed
      on days 1-5 after TBI. The mu receptor agonist, DAMGO significantly reduced both
      beam-walking latency and body weight loss after injury (p < 0.05). DAMGO-treated
      rats (n = 5) did not differ from CSF-treated rats (n = 5) on either systemic
      arterial blood pressure or heart rate responses to injury. Experiment II: Beta
      funaltrexamine (beta-FNA) (20.0 nMol in 5.0 microliters) (n = 10) or artificial
      CSF (n = 10) was administered (icv) to rats 5 min prior to fluid-percussion brain
      injury (1.8 atmospheres). Motor performance was assessed on days 1-5 after TBI.
      The mu receptor antagonist, beta-FNA, significantly increased beam-walking
      latency after injury (p < 0.05). beta-FNA-treated rats (n = 5) did not differ
      from CSF-treated rats (n = 5) on either systemic arterial blood pressure or heart
      rate responses to injury. Experiment III: Neither beta-FNA nor DAMGO affected
      motor performance in uninjured rats. These results suggest that activation of mu
      opioid receptors by exogenous agonists may provide protection against deficits in
      motor performance produced by fluid percussion brain injury.

PMID- 7566513
TI  - Evidence that endogenous substance-P (SP) is involved in the maintenance of the
      growth and steroidogenic capacity of rat adrenal zona glomerulosa.
AB  - A 7-day intraperitoneal infusion with the specific SP antagonist magnitude of D
      Pro4,D-Trp7,9-SP4-11 (SP-A; 0.3 nmol.kg-1.min-1) significantly lowered plasma
      aldosterone (ALDO) concentration and caused atrophy of adrenal zona glomerulosa
      (ZG) and its parenchymal cells. Dispersed ZG cells from SP-A-infused rats
      displayed a marked decrease in both their basal and maximally agonist-stimulated
      ALDO production. The simultaneous infusion of rats with SP (0.03 nmol.kg-1.min-1)
      completely annulled all these effects of SP-A. The plasma levels of ACTH and
      corticosterone, and the morphology of adrenal zona fasciculata were not affected
      by SP-A or SP-A plus SP infusion. These findings suggest that endogenous SP is
      specifically involved in the positive control of growth and secretion of the rat
      ZG.

PMID- 7566512
TI  - Vitamin D3 effects on basal and cAMP modulated expression of cholecystokinin and
      somatostatin genes in a rat medullary thyroid carcinoma cell line [CA-77].
AB  - The regulation of cholecystokinin and somatostatin expression by vitamin D and
      cyclic AMP in the rat medullary thyroid carcinoma cell line CA-77 was
      investigated. Treatment with 100 nmol/l vitamin D did not affect cholecystokinin
      mRNA and peptide concentrations significantly; somatostatin mRNA level increased
      6 times and the somatostatin peptide concentration increased 2-fold after 5 days
      of drug treatment. Under the same experimental conditions cyclic AMP increased
      cholecystokinin mRNA level 4.5 times and the cellular cholecystokinin-peptide
      concentration 2-fold; somatostatin mRNA and peptide concentrations were not
      significantly changed. Cyclic AMP stimulated peptide secretion from the cells
      were not affected by vitamin D, but cyclic AMP mediated increase in CCK peptide
      concentration was significantly inhibited by vitamin D (p < 0.05).

PMID- 7566515
TI  - Effects of guanyl nucleotides on CCKB receptor binding in brain tissue and
      continuous cell lines: a comparative study.
AB  - The effects of non-hydrolyzable guanyl nucleotide analogue GTP-gamma S on CCKB
      receptor binding in human and guinea-pig cortex, Jurkat T-cells, rat pituitary
      GH3 cells, rat glioma C6 cells and human small cell lung cancer NCI-H69 cells
      were investigated by using [3H]CCK-8S saturation and competition binding studies.
      GTP-gamma S caused inhibition of specific [3H]CCK-8S binding in a concentration
      dependent manner with a plateau at 10-25 microM. 25 microM GTP-gamma S resulted
      in a small but significant increase in Kd and IC50 values with amount very
      similar in all CCKB receptor models tested. However, the maximal number of
      specific [3H]CCK-8S binding sites (Bmax) was unaffected. Results suggest that
      CCKB receptors are G-protein coupled in a similar way to human and guinea-pig
      cortex, Jurkat cells, GH3 cells, C6 cells and NCI-H69 cells.

PMID- 7566514
TI  - Changes in neuropeptide levels after brain damage in rats.
AB  - The physiological and pathophysiological roles of neuropeptides are still not
      clear. The aim of our study was to detect long lasting changes of vasoactive
      intestinal peptide (VIP), somatostatin (SOM) and substance P (SP) contents in the
      rat cerebral cortex and hippocampus after brain lesion. The experiments were
      performed on groups of adult male Wistar rats. The first group consisted of
      animals with unilateral ablation of the sensorimotor cortex performed at the age
      of 60 days. The second group was a control one (rats of the same age but with an
      intact brain). Both groups of animals were sacrificed at the age of 90-105 days
      and radioimmunoassay was used to determine amounts of VIP, SOM and SP. The mean
      values of VIP levels were decreased significantly only in contralateral cortical
      areas, while there was an increase of SP in lesioned animals. Our results suggest
      that descrete changes in neuropeptide levels occur during restorative processes
      after brain lesion.

PMID- 7566516
TI  - Sleep EEG changes in psychotic disorders: gender and age effects.
AB  - The aim of this study was to examine gender-related differences in
      electroencephalographic (EEG) sleep in inpatients with psychotic disorders. We
      investigated the effects of gender and age as well as gender-by-age interactions
      on sleep continuity, architecture and intranight distributions in 38 male and 23
      female patients with functional psychoses. No gender effects were seen for any
      sleep parameters. However, older psychotic males had less slow-wave sleep than
      older psychotic females. On the other hand, female psychotic patients showed a
      significant decline in automated REM counts with age. It is possible that gender
      related differences in neurodevelopment and/or aging could account for these
      findings.

PMID- 7566517
TI  - Sodium-magnesium exchange in erythrocyte membranes from patients with affective
      disorders.
AB  - The Vmax of erythrocyte sodium-magnesium exchange was measured for the first time
      in 63 patients suffering from affective disorders and compared to that in 33
      healthy subjects. Depressed patients had a significantly higher Vmax (215 +/- 13
      vs. 151 +/- 14 mumol/l.cells/h; p < 0.005; mean +/- SEM). This tendency was
      conserved after division of the 63 patients into three clinical subgroups
      according to the DSM-III-R criteria. Thirty-four patients from this panel were
      divided into three subgroups according to the chemical class of the
      antidepressant drug used and were followed up during a 3-month period of drug
      treatment. Mood improvement over the 3-month period was associated with a slow
      increase in Vmax of Na/Mg exchange (delta increase approximately 25
      mumol/l.cells/h), except in the subgroup of patients treated with non-tricyclic
      antidepressants (n = 8). These results are consistent with the previously
      reported link between high erythrocyte magnesium content and affective disorders.
      Indeed, enhanced Na/Mg exchange Vmax, which probably results from an increased
      number of transport units per cell, contributes to the normalization of red blood
      cell magnesium content correlated with mood improvement.

PMID- 7566518
TI  - Effect of previous antidepressant therapy on the growth hormone response to
      apomorphine.
AB  - Several lines of evidence suggest a role for dopamine in the pathophysiology of
      depression. In 1988, we reported a blunted response of growth hormone (GH) to
      apomorphine, a dopaminergic agonist, in endogenous depression. However, an
      antidepressant washout period is a major confounding factor in studies assessing
      the GH response to apomorphine. Indeed, whereas the influence of tricyclic
      antidepressants on the GH response to apomorphine is presently unknown, several
      reports have suggested that tricyclics may impair the GH response to clonidine
      for periods longer than 3 weeks following their discontinuation. In the present
      study, we hypothesized that a blunted GH response to apomorphine in depressed
      patients could be related to the recent administration of antidepressants.
      Therefore, the GH response to apomorphine (0.5 mg) was studied in 11 male DSM-III
      R major depressive inpatients who had never received antidepressant therapy
      (group 1) compared to 11 normal controls and 11 major depressive inpatients drug
      free for at least 2 weeks (group 2). The three groups differed significantly in
      the GH peak response to apomorphine: mean (SD) 5.4 (4.0) ng/ml in group 1, 25.5
      (10.7) in normal controls, and 5.5 (5.1) in group 2 (F = 15.5, df = 3, 30, p =
      0.00001). While group 1 and normal controls (F = 21.8, p = 0.0002) as well as
      group 2 and controls (F = 5.6, p = 0.03) differed significantly, group 1 and
      group 2 did not (F = 0.18, p = 0.68). These results suggest that a washout period
      of 2 weeks could be sufficient in studies assessing the GH response to
      apomorphine.

PMID- 7566519
TI  - Are there any differences in the safety and efficacy of brofaromine and
      imipramine between non-elderly and elderly patients with major depression?
AB  - There is a rather limited database of controlled clinical trials on the
      comparative effects of antidepressants in elderly and non-elderly depressed
      patients. A common finding is reduced efficacy and an increased incidence of side
      effects. To further examine the question of efficacy and safety of antidepressant
      drugs in elderly versus non-elderly patients, the differential effects of a new
      selective type A monoamine oxidase inhibitor brofaromine, and the classical
      tricyclic imipramine were investigated using the data of two recently published
      trials. We found no major difference between non-elderly and elderly depressed
      patients as concerns efficacy, total incidence of adverse findings or safety
      parameters such as laboratory values and heart rate. These results are discussed
      in the light of some methodological questions and previous reports.

PMID- 7566520
TI  - Amnesia after diazepam infusion into basolateral but not central amygdala of
      Rattus norvegicus.
AB  - Recent findings indicate that the memory-impairing effects of benzodiazepines may
      preferentially involve the basolateral nucleus of the amygdala. To test this
      hypothesis we examined the effects on pretrial injection of diazepam into the
      central as compared to the lateral/basolateral amygdaloid nuclei on memory for a
      conditioned avoidance response. Rats were implanted bilaterally with cannulae
      directed to either the central or lateral/basolateral amygdaloid nuclei. Five to
      7 days later they were trained on a multitrial inhibitory avoidance (step-down)
      task to criterion and tested 48 h later. Fifteen minutes before training they
      were given an injection of either vehicle or diazepam (0.7 or 1.4 nmol) into the
      central or lateral/basolateral nuclei. Administration of diazepam into the
      lateral/basolateral nuclei but not the central nucleus induced anterograde
      amnesia. These results add to the body of data linking the GABA-benzodiazepine
      system of the lateral/basolateral nuclei to the amnestic effects induced by
      peripheral as well as central administration of benzodiazepines.

PMID- 7566521
TI  - Effect of sabeluzole (R 58,735) on memory functions in patients with epilepsy.
AB  - Sabeluzole, a new benzothiazol derivative, has shown positive effects on memory
      function in animals and in normal volunteers. The present study reports the
      results of sabeluzole, in memory-impaired patients with localization-related
      (partial) epilepsy. A randomized, double-blind placebo-controlled parallel-group
      design was used. A total of 38 patients entered a prospective baseline. Five
      patients dropped out from the study, thus 33 patients were randomly assigned to
      either a 12-weeks treatment with sabeluzole (n = 14) or placebo (n = 19). The
      treatment phase was preceded by a titration phase of 4 weeks to obtain serum
      levels of sabeluzole between 50 and 130 ng/ml. In order to maintain blindness, a
      sham titration was carried out in the placebo group. The number of 'responders',
      i.e. patients with a > 1 SD improvement on at least three of the memory tests was
      9 out of 14 (64.3%) in the sabeluzole group and 7 out of 19 (36.8%) in the
      placebo group. This suggests a clinically relevant effect of sabeluzole. The
      analysis of the memory tests showed a statistically significant improvement with
      sabeluzole on the verbal long-term memory test. This could represent a specific
      drug effect and is in line with previous results of normal volunteer studies that
      also found improvement mainly restricted to the area of verbal long-term memory.

PMID- 7566522
TI  - Bivariate global frequency analysis versus chaos theory. A comparison for sleep
      EEG data.
AB  - Various quantitative descriptors for EEG data will be compared taking sleep as an
      example. In this contribution, Hjorth's mobility and complexity measures will be
      used to classify sleep stages. The results will be compared with those of a
      dimensionality analysis. Several authors have shown that the correlation exponent
      can describe the complexity of sleep EEG data and is able--with the exception of
      REM sleep--to distinguish significantly between sleep stages. The discriminative
      power of a bivariate global frequency analysis appears to be superior to that of
      the correlation exponent. Furthermore a very high statistical correlation between
      the estimator of fractal dimension and Hjorth's mobility was obtained.

PMID- 7566523
TI  - Analysis of event-related potentials: a physiological interpretation.
AB  - A physiological interpretation is presented of ERP parameters, in relation to
      their origin. This interpretation is based on the type of the electric
      contribution of every active neuron to the ERP wave registered. Through the solid
      angle theorem it is shown that an active neuron contributes to the ERP with a low
      electric potential while its activation lasts. This gives a physiological meaning
      to the parameters which describe the ERP wave.

PMID- 7566524
TI  - Peripheral serotonin in Alzheimer's disease.
AB  - The platelet has been suggested to be a peripheral model of the central
      serotonergic neuron. This investigation was carried out in order to test the
      hypothesis that levels of serotonin (5-HT) in the platelet will be decreased in
      Alzheimer's disease (AD) since neurochemical studies suggest that levels of 5-HT
      are decreased in the brain of AD patients. We investigated platelet and plasma 5
      HT in a group of AD patients (n = 22) as well as in age-matched normal control
      subjects (n = 20). The results show that the platelet level of 5-HT was
      significantly reduced in AD (65.7 +/- 28.41 ng/10(8) platelets in AD vs. 112.9 +/
      35.11 ng/10(8) platelets in controls; p = 0.0001). There was no effect on the
      levels of its metabolite 5-hydroxyindoleacetic acid. These findings suggest that
      the peripheral serotonergic system in AD is adversely affected.

PMID- 7566526
TI  - Titanium intervertebral disc and instrumentation for fusion in anterior cervical
      discectomy. Technical note.
AB  - A new titanium intervertebral disc for fusion in anterior cervical discectomy is
      described. The advantages of the device, apart from avoidance of graft
      explanation, include biocompatibility, simple instrumentation, availability of
      different forms and sizes, and restoration of physiologic lordosis. Following
      extensive biochemical testing and implantation in animals, first long-term
      experience in 15 patients with an average follow-up of three years (28-73 month)
      are described. Infections, anterior angulation deformities, and graft extrusions
      were not observed in this series.

PMID- 7566525
TI  - Target point calculation in the computerized tomography. Comparison of different
      stereotactic methods.
AB  - The adaptation of computerized tomography for stereotactic operations requires
      the transformation of the coordinates of the target point from the CT image space
      into the stereotactic frame space. Two basic solutions for this transformation
      are realized in the most of the contemporary stereotactical systems. The indirect
      geometric method adjusts the frame coordinate system mechanically and identifies
      its origin in the CT image. There are 6 degrees of freedom: 3 of rotation and 3
      of translation which have to be taken into consideration. The second method is a
      based on direct algebraic coordinate transformation and is independent of the
      explicite knowledge of the relationship between the image and the frame space. A
      localization frame serves to determine a transformation matrix which, applied to
      any point in the image, transforms the coordinates directly into the frame
      coordinate system. Only the algebraic method is independent of the position of
      the patient in the gantry. All other methods require high mechanical precision of
      the alignment and stability for the CT table.

PMID- 7566527
TI  - Percutaneous needle trephination for external CSF drainage: experience with 226
      punctures.
AB  - We report on our experience with 226 percutaneous needle trephinations in a total
      of 192 consecutive patients. Trephination was performed with a hand-driven drill.
      A special puncture needle was inserted into the anterior horn of the lateral
      ventricle. The main indication for this procedure was the treatment of occlusive
      hydrocephalus in an emergency. Duration of drainage ranged from 1 to 34 days and
      was 7 days on the average. We encountered 14 cases of infection (6.2%) and one
      case of symptomatic bleeding (0.4%). All these complications eventually resolved
      without permanent sequelae. In our opinion, ventricle puncture with this device
      is a simple and effective method and can especially be recommended for external
      CSF drainage in cases of emergency.

PMID- 7566529
TI  - Combined occurrence of primary cerebral lymphoma and meningioma.
AB  - A unique combination of primary cerebral lymphoma and meningioma was encountered
      in a 38-year-old woman who recently presented clinically with headache and
      papilledema. The both tumors were identified by CT scan and diagnosed
      histopathologically after the surgery. The association of a highly malignant
      primary cerebral lymphoma and a slowly growing meningioma is extremely rare. The
      possibility of an unknown underlying pathologic mechanism predisposing to
      multiple tumors should be considered.

PMID- 7566528
TI  - Correlation of alterations on Na(+)-K+/Mg+2 ATPase activity, lipid peroxidation
      and ultrastructural findings following experimental spinal cord injury with and
      without intravenous methylprednisolone treatment.
AB  - The sodium-potassium activated and magnesium dependent adenosine-5'
      triphosphatase (Na(+)-K+/Mg+2 ATPase EC 3.6.1.3.) activity and lipid peroxidation
      and early ultrastructural findings are determined in rat spinal cord at the early
      stage of trauma produced by a surgical clip on the thoracal 2-7 segments. The
      effect of treatment with intravenous methylprednisolone (MP) was evaluated the
      basis of these biochemical alterations and ultrastructural findings in the same
      model. The specific activity of the membrane bound enzyme Na(+)-K+/Mg+2 ATPase
      was promptly reduced in as early as ten minutes following spinal cord injury and
      remained at a level lower than the levels in the control group and in the sham
      operated group. Methylprednisolone treatment immediately after the trauma
      attenuated the inactivation of Na(+)-K+/Mg+2 ATPase. On the other hand, there was
      significant difference in lipid peroxide content between the sham-operated and
      the injured animals. Methylprednisolone treatment reduced thiobarbituric acid
      reactive substance (TBARS) content in Group IV. We determined a positive
      relationship among membrane-bound enzyme Na+K+/Mg+2 ATPase activity,
      malondialdehyde (MDA) content and early ultrastructural changes in the
      traumatized and treated groups.

PMID- 7566530
TI  - Familial hypercholesterolemia and intracavernous venous spilling of cholesterol
      in a child with large suprasellar dermoid cyst. Case report.
AB  - A unique case of suprasellar dermoid cyst and familial hypercholesterolemia in a
      child is reported. Such an association, which strengthens the congenital
      hypothesis of dermoid cysts, could be a manifestation of a complex dyslipidemic
      inherited syndrome, at least in children. Surgical removal of the dermoid cyst
      which spilled cholesterol into the cavernous and intercavernous sinuses, allowed
      reduction of cholesterol levels in the postoperative period.

PMID- 7566532
TI  - Intraosseous cavernous hemangioma of the skull.
AB  - Intraosseous cavernous hemangioma is a vascular tumor that only rarely affects
      the cranial bones. We describe three patients with this unusual tumor and discuss
      the clinical and radiological features of this lesion in the light of published
      data.

PMID- 7566533
TI  - A long-term complication of burying a shunt valve in the skull.
AB  - One of the most common causes of shunt malfunction is infection; a major
      contributing factor to this infection in neonates is scalp necrosis over the
      valve site. One of the methods recommended to avoid this requires the burying of
      the valve in the skull bone. We present a case of a long-term complication from
      this procedure: the shunt slowly disconnected, over a prolonged period, leading
      to the formation of the fibrous tunnel which enabled the shunt to function
      intermittently. We recommend that the practice of burying the shunt into the
      skull bone is be reconsidered.

PMID- 7566534
TI  - Effect of balloon angioplasty on high grade symptomatic vasospasm after
      subarachnoid hemorrhage.
AB  - Of 455 cases of ruptured intracranial aneurysm treated with radical surgery from
      January 1987 to March 1992, 19 cases with high grade symptomatic vasospasm were
      treated by percutaneous transluminal balloon angioplasty (PTA). The indication
      for PTA was high grade symptomatic vasospasm which does not respond to
      conservative medical treatment. Of the 36 segments of vasospastic arteries,
      severe vasospasm (angiographical constriction more than 50% of diameter on
      admission) was observed in 67%. PTA dilated these vasospastic arteries
      significantly (diameter of more than 75% of diameter on admission) in 83%. Follow
      up angiography revealed neither recurrence of vasospasm nor chronic
      atherosclerotic changes. Clinical improvement within 24 hours after PTA was
      observed in 63% of cases (7 of 17 cases with consciousness disturbance, 5 of 16
      cases with motor weakness and one of 7 cases with aphasia). Outcomes at the time
      of discharge were excellent in 10 cases, good in 3, fair in 4, and lethal in 2.
      SPECT study before and after PTA confirmed improvement of cerebral blood flow in
      3 out of 5 cases investigated. PTA for high grade symptomatic vasospasm after
      subarachnoid hemorrhage is considered an effective treatment method for the
      patient who does not respond to medical therapy. Immediate improvement of
      angiographical and clinical findings were frequently observed immediately after
      PTA. Exact indication and timing of PTA should be postulated after much more
      cases have been treated with this methal.

PMID- 7566531
TI  - Spinal epidural hematoma. Report of a case and review of the literature.
AB  - We report the case of a thoracic epidural hematoma at the T7-T9 level which
      occurred after placement of spinal epidural catheter for continuous anaesthesia
      in acute pancreatitis. The male patient felt a sudden back pain after six days of
      successful analgesia and became paraplegic 24 hours afterwards. An emergency
      laminectomy and removal of the hematoma were performed; however, the patient
      recovered only incompletely. We discuss the clinical signs and symptoms of spinal
      epidural hematoma as well as its diagnostics and therapy. The controversial views
      from the literature concernings its etiology are critically reviewed.

PMID- 7566535
TI  - Incidence and complexity of ventricular ectopy during Holter monitoring in
      patients with exercise-induced myocardial ischemia and normal or mildly reduced
      left ventricular function.
AB  - We aimed to assess the relationship between frequent and complex ventricular
      ectopy by continuous electrocardigraphic 24-hours Holter monitoring in patients
      with coronary artery disease and inducible ischemia during exercise procedures.
      We investigated 609 consecutive patients. They were referred for chest pain (28%
      with a previous myocardial infarction, older than 6 months). In all population
      patients radionuclide ventriculography showed a global normal or mildly reduced
      left ventricular function (ejection fraction > 45%). All patients showed exercise
      induced myocardial ischemia (ST depression) and exercise thallium-201 reversible
      defects. During Holter monitoring, in study population, divided according to
      incidence of premature ventricular complexes (PVC), we found a higher prevalence
      of complex ventricular arrhythmias (CVA) (bigeminy, couplets, ventricular
      tachycardia, multiformity) in patients with high incidence of PVC. The
      relationship between frequent and complex ventricular ectopy has been observed
      also during ischemic ST shifts occuring during 24-hours monitoring. In contrast,
      the R on T phenomenon was not related to incidence of PVC. Therefore, in patients
      with exercise-induced myocardial ischemia and global normal or mildly reduced
      left ventricular function there is a relationship between frequent and complex
      ventricular ectopy, as previously suggested in CAD patients with depressed left
      ventricular function.

PMID- 7566536
TI  - [Role of MB-mode transthoracic echography in the early diagnosis of acute
      pulmonary embolism].
AB  - The aim of the present study was to evaluate whether transthoracic
      ecocardiography M-B mode was a sensitive and/or specific test for the early
      diagnosis of acute pulmonary embolism (PEA). For this purpose, we studied 7
      patients with PEA as a complication of: deep leg venous thrombosis (3 cases),
      complicated bone fractures (2 cases), meniscectomy (1 case) and postpartum (1
      case). The patients (3 males and 4 females), mean age of 46 +/- 7 years, did not
      have any previous earlier heart and/or pulmonary diseases. The diagnosis of PEA
      was made on the basis of clinical criteria, ecg and laboratory tests.
      Ecocardiography was performed using an IREX 3 M-B mode equipment; the
      measurements for the calculation of the indexes were made utilizing a short axis
      parasternal window. The parameters studied were: RVEDD/LVEDD ratio, LVDI Okubo
      index and the TR grade. Data were analyzed employing the paired Student's t test.
      In all patients was observed a statistically significant enlargement on the right
      heart cavities; while only in 3 of them was it possible to observe a slight
      reduction of the left ventricular cavities. In conclusion, the ecocardiographic
      exam was is a sensitive test for the diagnosis of PEA. Particularly, the
      RVEDD/LVEDD ratio gave an early and quantitative indication of the obstruction
      severity. Indeed, the morphological alteration of the right cavities became
      evident when the embolic obstruction was of at least 30%. Hence, we suggest that
      the standard ecocardiography M-B. mode may be regarded has a rapid diagnostic
      tool for the diagnosis of PEA.

PMID- 7566537
TI  - [Use of PGE1 in severe ischemia of the lower extremities. Clinical study].
AB  - Lower limb critical ischemia is a clinical condition typical of patients with
      severe chronic obstructive arterial disease (Fontaine's IIIb and IV degree). This
      condition often leads to amputation of the limb involved. The authors present to
      the use PGE1 in 50 patients with Fontaine's IIIb-IV degree chronic obstructive
      arterial disease of lower limbs in which the indication of amputation was done.
      All the patients, admitted to the emergency ward, complain of rest pain and
      distal ulcers. The administration of PG5(1) was given as follows: 40
      mg/bid/e.v./20 days. A 6 months long follow-up was installed with the
      instrumental evaluation of: Transcutaneous oxygen pressure; Distal blood
      perfusion with Doppler; cardiac pulse; blood pressure. Eighteen patients became
      to a Fontaine's II degree during the next 2 months after therapy, 25 patients
      came back to a severe claudicatio: of them 18 underwent successfully vascular
      surgery, 7 underwent amputation of the lower limb. In 7 patients the PGE1 did not
      influence the natural progression of the disease. Among the side-effects of
      therapy we can mention: headache (4%), erythema and pain of injected vein (8%),
      sick (4%). All the side effects were transient and never led to interruption of
      therapy.

PMID- 7566539
TI  - [Nisoldipine in the treatment of ischemic cardiopathy in the aged. Study of
      electric systole].
AB  - The authors examine the behaviour of electric systole during nisoldipine
      treatment using doses of at least 10 mg/die in association with modifications of
      ischemic signs recorded using surface ECG in a series of 70 elderly patients.
      Patients were subdivided into three groups according to the results obtained from
      a comparison of real electric systole (QT) with that corrected for ventricular
      frequency (Qtc), as well as the difference expressed in mean values (VM). 1)
      Patients with elongated QT. Following nisoldipine treatment this group showed a
      mean elongation of electric systole of 0.393" +/- 0.025 with a R correlation
      index between electric systoles before and after treatment of 0.633" which
      expresses the amplitude of the elongation for each starting QT unit (p < 0.001).
      The mean value in the two conditions increased from -1.381 +/- 2.111 contraction
      units to 3.568 +/- 2.697 elongation units and mean deviation was 4.886 +/- 2.170
      units with an absolute value of 211.0 units which expresses the elongation of the
      electric systole in the overall sample compared to calcium antagonists as an
      iatrogenic phenomenon. Ischemic signs improved or disappeared in 40 out of 44
      cases (90.91%) for the T wave and in 36 out of 41 cases (87.80%) for the ST
      tract. 2) Patients with normalised QT. In 6 cases which showed elongated
      pretreatment electric systole, it was observed that values became normal passing
      from a mean of 0.390" +/- 0.40 to 0.377" +/- 0.053. Mean deviation diminished
      from 3.833 +/- 0.983 units to 1.333 +/- 1.211 units with statistical significance
      only for paired data in 2 groups (p < 0.001), without correlation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7566538
TI  - [Behavior of endothelin plasma levels during iloprost infusion in patients with
      severe ischemia in the lower extremities].
AB  - In order to clarify interactions between the various endothelial vasoactive
      substances, the authors studied the behaviour of endothelin plasma levels during
      acute iloprost infusion in 7 elderly patients with critical leg ischemia.
      Iloprost was administered i.v., diluted in saline solution (200 ng/ml, from 30 to
      40 ml/h, for 6 hours/day over 4 weeks). Endothelin was assayed in plasma on day 4
      of treatment at times 0, 2, 4, 6, 8, hours, or in other words before treatment
      and ten every 2 hours up until the 6th hour, and then 2 hours after the end of
      iloprost infusion. The control group consisted of 7 age-matched subjects
      suffering from peripheral obliterating arterial disease at Fontaine's stage 1 and
      2 who where infused with saline solution alone. Patients receiving iloprost
      presented a mean endothelin plasma level +/- SD at time 0 of 5.40 +/- 1.23 pg/ml,
      4.24 +/- 0.72 pg/ml at time 2, 4.22 +/- 0.74 pg/ml at time 4, 4.24 +/- 0.22 pg/ml
      at time 6, and 4.49 +/- 0.58 pg/ml at time 8. The difference between endothelin
      levels in basal conditions and those at time 2, 4 and 6 was statistically
      significant. The difference between the peptide at times 0 and 8 was not
      statistically significant. In the control group the mean +/- SD of endothelin
      plasma level was, at the same times, respectively 5.23 +/- 0.55 pg/ml, 4.88 +/-
      1.39 pg/ml, 5.44 +/- 1.51 pg/ml, 5.10 +/- 0.86 pg/ml and 5.60 +/- 1.64 pg/ml. The
      difference between endothelin levels in basal conditions and those at later times
      was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566540
TI  - [Current views on the use of vasodilators in pulmonary hypertension].
AB  - Vasodilators represent one of the main steps for the medical treatment of
      pulmonary hypertension; the rationale for their use is the reversibility of the
      pulmonary vasoconstriction, to be tested with a correct pharmacological trial. In
      this report the authors consider the use of calcium-channel blockers,
      prostaglandin and nitric oxide. Calcium blockers, the only drugs active when
      administered orally, provide a satisfactory clinical response in 25-30% of
      treated patients. Prostaglandins are active in a higher percentage of patients
      and can be infused in a domiciliary regimen with portable pumps even for long
      periods of time. Nitric oxide is the only selective pulmonary vasodilator; it is
      used in paediatric and adult cardiac surgery and in patients affected by
      respiratory distress syndrome, but its use is restricted to intensive care units
      and many cautions must be adopted. Finally some future therapeutic strategies are
      briefly reviewed: endothelin inhibitors, cGMP phosphodiesterase inhibitors etc.

PMID- 7566542
TI  - [Aneurysm of the popliteal artery in a patient over 80 years of age].
AB  - The authors report an aneurysm in the popliteal artery surgically treated with
      success. The operation consisted on the installation of one tubular prosthesis
      femoro-poplitea with a termino-terminal anastomosis. The follow-up to 3 and 6
      months from the operation showed good functional recovery.

PMID- 7566541
TI  - [Colchicine in the treatment of idiopathic recurrent pericarditis. Report of a
      case].
AB  - Treatment of recurrence, which is one of the major complications of pericarditis,
      is often difficult. After three recurrences of idiopathic acute pericarditis,
      over a period of four months, despite therapy with acetylsalicylic acid,
      indomethacin and methilprednisolone, a patient, 37 years old, responded favorably
      to colchine treatment. No recurrences, no side effects were observed, after a
      prolonged low dose treatment. Our report suggests, therefore, that colchinine may
      be beneficial in acute attacks of idiopathic pericarditis and may be useful in
      avoiding recurrent episodes of pericarditis.

PMID- 7566543
TI  - Who sleeps by whom revisited: a method for extracting the moral goods implicit in
      practice.

PMID- 7566544
TI  - Development through participation in sociocultural activity.

PMID- 7566545
TI  - Precepts and practices: researching identity formation among Indian Hindu
      adolescents in the United States.

PMID- 7566546
TI  - Cultural practices and the conception of individual differences: theoretical and
      empirical considerations.

PMID- 7566547
TI  - Familial and ecological correlates of self-esteem in African American children.

PMID- 7566548
TI  - [Mixed cryoglobulinemia and the hepatitis C virus].
AB  - Mixed cryoglobulinemia is a cryoprecipitable immune-complex mediated disease, in
      which cryoglobulins are type II and III of the immunochemical classification of
      Brouet. Essential mixed cryoglobulinemia, in opposition to secondary, is
      characterized by the absence of well-defined underlying disease and clinically it
      shows the classical triad of Meltzer and Franklin. Several reports point to the
      frequent, through various, liver involvement in essential-defined mixed
      cryoglobulinemia. Particularly, the clinical and biological evidence of liver
      disease is commonly soft, in spite of the common bioptic evidence of persistent
      or chronic active hepatitis. The problem about which comes first in this
      association had been widely investigated, including the possible pathogenetic
      role of hepatotropic viruses. Initially some studies focused attention on
      hepatitis B virus, but now its importance is de-emphasized because of critical
      epidemiological review, results of HBV-DNA in cryoprecipitates, electron
      microscopy data. The recent opportunity of diagnostic tests for hepatitis C virus
      gave proof of its great importance in apparently essential mixed
      cryoglobulinemia. In fact, many researches have found a variously high prevalence
      of anti HCV antibodies and HCV-RNA in serum and cryoprecipitates, with selective
      concentration in the latter. Alpha interferon treatment has been suggested as
      first choice drug in the management of HCV related cryoglobulinemia. The
      mechanism is postulated to be primarily due to its antiviral activity. Up to date
      optimal dose and treatment period needs to be established.

PMID- 7566549
TI  - [An epidemiological study on blood viscosity and intraerythrocytic calcium in a
      group of high-school students selected according to their family histories].
AB  - An epidemiological study was performed in a group of secondary school students
      selected according to their family history to assess whether changes exist in
      blood viscosity and intraerythrocytic calcium levels in young healthy subjects
      with positive family histories of arterial hypertension or cerebral and cardiac
      ischemic vasculopathies, compared to a control group with a negative family
      history of these disorders. A population of 130 secondary school students without
      any pathologies were subdivided into 4 groups: 1) with a positive family history
      of ischemic cardiopathy (ICP); with a positive family history of cerebral ictus;
      3) with a family history of arterial hypertension; 4) a negative family history
      of these diseases. Total blood viscosity, hematocrit, plasma fibrinogen and
      intraerythrocytic calcium was evaluated in all groups. The results show that
      these parameters were within the normal range, as was to be expected in healthy
      subjects. Blood viscosity was also normal in all groups; intraerythrocytic
      calcium levels were slightly higher in groups with histories of cardiovascular
      disease and in particular there was an increased percentage of cases with values
      above the threshold level. Higher fibrinogen levels were also recorded, but
      always within the normal range, in the group with a positive history of ICP. The
      epidemiological study is important to assess whether a family pattern of
      cardiovascular disease can also influence such independent risk parameters as
      blood viscosity and intraerythrocyte calcium, owing to the possible greater
      frequency of development of cardiovascular disease.

PMID- 7566550
TI  - [An increase in bile acids in the serum of patients with chronic kidney failure].
AB  - Measurement of serum bile acids was performed in 86 uremic patients without any
      liver or bile tract diseases. Thirty-six patients (23 males and 13 females, aged
      21-60 years) were on conservative dietary treatment, whereas 50 uremics (31 males
      and 19 females, aged 23-82 years) were on maintenance hemodialysis. The assays
      were made by means of enzymatic procedure and confirmed by RIA method too.
      Elevated serum concentrations of bile acids (> 6 mumol/L) were found in 24 out of
      the 86 uremics (27.9%), and the prevalence was similar in patients on
      conservative (10/36, 27.7%) and on dialysis treatment (14/50, 28%). Then,
      abnormally elevated concentrations of circulating bile acids are present in a
      quite high percentage of uremics both on hemodialysis and on conservative dietary
      therapy. The existence of a subclinical liver disease or an abnormal entero
      hepatic cycle of bile acids might explain these findings.

PMID- 7566551
TI  - [Abdominal aortic aneurysm in the elderly].
AB  - AIM: Complication-free abdominal aortic aneurysm is often asymptomatic and its
      diagnosis is therefore frequently coincidental. Abdominal aortic aneurysm (AAA)
      is often suddenly manifested during the rupture stage, resulting in the patient's
      death. The importance of early diagnosis is therefore clear, enabling optimal
      monitoring and correct management. EXPERIMENTAL DESIGN AND SUBJECTS: This
      retrospective study evaluated the incidence of AAA in 1304 over-65-year-olds in
      care. The authors examined the presence of AAA-related symptoms, risk factors and
      the concomitance of other pathologies. RESULTS: Four subjects were diagnosed with
      AAA, equivalent to 0.3% of the total population. All were male, smokers, with
      multidistrict atherosclerosis in association with other pathologies. CONCLUSIONS:
      The incidence of AAA in the population of over-65-year-olds examined was lower
      than that reported in the literature. This discrepancy was due to the fact that
      the abdominal aorta is not usually examined in clinical practice. However, the
      high mortality rate of AAA during rupture prompted the authors to evaluate this
      disorder in high-risk patients.

PMID- 7566552
TI  - [The measurement of outcomes in chronic pathology. Its application to arthritis].

PMID- 7566553
TI  - [Mixed IgM kappa-IgM lambda cryoglobulinemia with a double monoclonal serum
      component. A case report].
AB  - The paper describes a case of mixed cryoglobulinemia with a double serum
      monoclonal component. The serum immunofixation revealed that a monoclonal
      component was IgG lambda while the other was positive for antisera anti-IgM, anti
      k and anti-lambda even if the EP proved monoclonal. Resuspended cryoglobulins had
      the same electrophoresis pattern and the same reactivity for the antisera as the
      IgM serum component.

PMID- 7566554
TI  - [Multiple sclerosis. A report of a case treated with thymopentin].
AB  - The authors analyse the case of a 58-year-old male suffering from substantially
      "atypical" multiple sclerosis (MS), both in terms of the late onset and because
      of some characteristics of the course of disease. The patient was treated with a
      subcutaneous immunomodulator (thymopentin) at a dose of 50 mg/day in 3-monthly
      cycles with intervals of 2 months between cycles, for a total of 3 cycles.
      Instrumental (CAT-NMR) and laboratory (immunological) tests were not significant,
      whereas others provided complex responses that allowed the presence of a
      demyelinating syndrome to be ascertained, above all due to the positivity of
      isoelectrofocusing. Treatment with thymopentin, commenced 12 years after the
      clinical onset of disease and after numerous cycles of cortisone and ACTH
      therapy, led to a major improvement in clinical conditions, especially of
      "sthenia" and movement, with consequent recovery of personal autonomy and working
      capacity which had previously been totally lost. Immunological tests performed at
      the end of each treatment cycle showed some slight but interesting modifications
      in parameters relating to DNA and the percentage of HLA antigens bound to
      lymphocytes. These findings suggest that the patient's immune system was
      sensitive to treatment with the thymic hormone responsible for the objective
      clinical improvement. These results appear to open the way to the possible
      treatment with immunomodulators.

PMID- 7566557
TI  - [Osteoporosis and densitometry screening: preliminary results].
AB  - We have examined the bone densitometry with osteoradiometer (ORM) of 355 patients
      who came to the "Centre for Prevention, Diagnosis and Therapy of Osteoporosis" at
      the Israelitic Hospital of Rome. 144 patients, 141 females and 3 males, will be
      studied in the future because their densitometric values are lower than the
      values considered normal for age and sex. We have valued anamnestic data (age,
      menopause, pregnancies, excessive use of alcohol and smoke, sedentary habits),
      medical data hyperthyroidism, OCB, chronic diarrhoea) and surgical data
      (ovariectomy, thyroidectomy, gastro-duodenal resection, mastectomy) to have the
      correct outline of the patient situation before further researches and beginning
      the best medical therapy. For the prevention and screening of people "at risk"
      densitometry is irreplaceable both pre-clinical osteopeny, and for checking the
      effects of the therapy.

PMID- 7566555
TI  - [Multiple gangrenous lesions of the scalp in a case of cranial arteritis].
AB  - A case of a patient with headache, visual deficiency in his left eye quickly
      worsening up to blindness and ischemic necrosis in the scalp regions supplied by
      the superficial temporal arteries, is reported. This acute gangrene began as a
      bandlike ischemic lesion in the temporo-parietal regions of both sides, rapidly
      enlarged, and acquired bizarre irregular outlines. Laboratory investigations and
      particularly superficial temporal artery biopsy confirmed the diagnosis of
      Horton's temporal arteritis, in accordance with the anamnestic and clinical data
      assessed at admission.

PMID- 7566556
TI  - [Robotics serving the elderly and the handicapped].
AB  - Recent data collected by the Japanese government confirm that our society is
      destined to become a high elderly dominated society. Forecasts show that by 2010
      approximately 21% of the population in countries such as France, USA and Japan
      will be over 65 years old. It is therefore becoming increasingly urgent to solve
      the problem of integration for the elderly and disable within the socioeconomic
      structure. The authors tackle the question of how service robots may be applied
      to resolve this problem. This paper presents a rapid overview of the most recent
      applications of robotics to the field of services for the elderly and disabled,
      paying particular attention to research carried out at the Laboratory of
      Robotics, Department of Mechanics of Milan Politecnico by Prof. S. Rovetta.

PMID- 7566558
TI  - [Relationship between cholesterol levels and depression in the elderly].
AB  - The aim of our study is to evaluate the possible association between lower plasma
      cholesterol and depression in the elderly. 140 subjects over 65 years old of both
      sexes were enrolled, of which 60 were affected by depression (DSM-III-R and
      Hamilton test) and 80 composed a control group homogeneous for sex and age with
      the previous one. Plasma cholesterol, HLD-cholesterol (HDL-C), LDL-cholesterol
      (LDL-C) and triglycerides were measured. A statistically significant difference
      between cholesterol and LDL-C (p < 0.001) was noted in the total group, in both
      males and females. Such modifications were independent of sex. In the group with
      lower cholesterol (cut-off < = 160 mg/dl) a prevalence of depression three times
      greater than subjects with higher cholesterol was found. In conclusion, the
      authors recommended a prudent use of lipid-lowering medications in the elderly
      because of its uncertain benefits.

PMID- 7566559
TI  - Interictal abnormalities of regional cerebral blood flow in migraine with and
      without aura.
AB  - Some controversial issues exist whether regional cerebral blood flow (rCBF)
      changes are present both in migraine with and without aura during the interictal
      period. For this reason we have studied rCBF characteristics in migraine patients
      when headache-free. rCBF examinations were performed by the 133Xe inhalation
      method on 39 normal subjects (24 aged 45 or less and 15 older than 45), on 10
      migraine patients with (A+) and on 10 without (A-) aura. The values of each
      patient were compared with the age-matched control population mean by a computer
      assisted mapping system that allows statistical analysis in real time. To compare
      inter-individual variability 10 subjects, out of 39 normals, constituted an age-,
      sex- and CO2-matched control group (C). 8 A+ patients and 7 A- showed significant
      alterations of CBF in comparison with the age-matched control population. The
      analysis between the age-, sex- and CO2 matched groups showed significant
      differences of the inter-hemispheric (F = 6.669, p = 0.004) and of the frontal (F
      = 7.480 p = 0.0008) asymmetries. These data show that in the headache-free period
      a derangement of the cerebral perfusion is present in both migraine with and
      without aura, suggesting they are due to the same disease process. Furthermore
      they show the usefulness of a computer-assisted mapping system, suitable for
      clinical use, in discovering small alterations in cerebral perfusion.

PMID- 7566560
TI  - [Sex hormones, glycolipid metabolism, and atherogenesis].
AB  - The prevalence of coronary artery disease is lower in women than in men. Ovarian
      estrogen is believed to decrease the risk of coronary heart disease. Today, there
      is an increasing demand for estrogen replacement not only for amelioration of
      menopausal subjective symptoms but also for the prophylactic action of estrogen
      against osteoporosis in postmenopausal women. Is generally agreed that estrogen
      replacement therapy reduces cardiovascular morbidity and mortality in
      postmenopausal women. Estrogen replacement therapy may protect against coronary
      heart disease by altering plasma lipoprotein concentrations, by increasing HDL
      cholesterol and decreasing LDL cholesterol, and thereby inhibiting progression of
      coronary artery atherosclerosis. Oral contraceptive can induce deterioration in
      glucose tolerance that has consistently been associated with insulin excess and
      insulin resistance. This situation can increase the coronary heart disease risk.
      New findings suggest that there may be independent cardioprotective effects of
      estrogen, such a direct inhibitory influence on thrombosis, vasospasm or
      atherogenesis, inhibiting atherosclerotic plaque formation in arterial walls.

PMID- 7566561
TI  - Zinc and the elderly.
AB  - It is frequent in the elderly a zinc deficit, for many causes, which frequently
      occur in old age. Mineral deficit cause humoral and cellular immunity depression,
      with large increase of susceptibility to infections and increase of morbidity and
      mortality; besides it increases the proteinic malnutrition so frequent in old
      people. This condition is particularly presented in surgical patients and in
      patients undergoing total parenteral nutrition, when not specifically zinc
      supplemented. The evaluation of plasmatic zinc for diagnostic aims is scarcely
      significant, because hypoproteinemia (above all, hypoalbuminemia) is constantly
      present in old people: more useful and important is the leucocytic mineral
      evaluation, particularly in polymorphonuclear neutrophils. The average of
      recommended daily allowance of zinc is 15 mg for elderly people.

PMID- 7566562
TI  - Atherosclerotic renal artery stenosis--when is intervention by PTA or surgery
      justified?

PMID- 7566564
TI  - The effect of ACE inhibitors and other antihypertensive agents on insulin
      resistance.

PMID- 7566565
TI  - Acute renal failure in glomerular bleeding: a puzzling phenomenon.

PMID- 7566563
TI  - Is the 'wait-and-see' approach justified in atherosclerotic renal artery
      stenosis?

PMID- 7566566
TI  - High frequency of papillary renal-cell tumours in end-stage kidneys--is there a
      molecular genetic explanation?

PMID- 7566567
TI  - Dialysis sodium concentration: what is optimal and can it be individualized?

PMID- 7566568
TI  - What stimuli control the activity of the parathyroid cell?

PMID- 7566569
TI  - Biomechanical stability of the skeleton--it is not only bone mass, but also bone
      structure that counts.

PMID- 7566570
TI  - Poor response to erythropoietin: practical guidelines on investigation and
      management.

PMID- 7566571
TI  - On-line monitoring.

PMID- 7566572
TI  - Impairment of endothelium-dependent vasorelaxation in chronic two-kidney, one
      clip hypertensive rats.
AB  - The present study was to investigate a role for endothelium-derived nitric oxide
      (EDNO) system in the development and maintenance of 2-kidney, 1 clip (2K1C)
      hypertension. Effects of blocking the synthesis or supplementing the precursor of
      EDNO on the developmental phase of hypertension were examined in 2K1C rats.
      Responses of the isolated vasculature to phenylephrine, acetylcholine, sodium
      nitroprusside, and atrial natriuretic peptide were also examined in chronic 2K1C
      rats. Ingestion of NG-nitro-L-arginine methyl ester or L-arginine did not affect
      the development of hypertension in 2K1C rats. Contraction response to
      phenylephrine was enhanced and relaxation response to acetylcholine was
      attenuated in the thoracic aortic ring isolated from chronic hypertensive rats,
      both being more marked in the 12-week hypertensive than in the 7-week
      hypertensive. Indomethacin did not significantly affect the degree of the
      attenuated vasorelaxation response to acetylcholine. The vasorelaxation response
      to sodium nitroprusside and atrial natriuretic peptide remained unaltered in the
      hypertensives. These results indicate that EDNO does not affect the developmental
      phase of 2K1C hypertension, whereas an impaired endothelium-dependent
      vasorelaxation is associated with chronic 2K1C hypertension.

PMID- 7566573
TI  - Reversible acute renal failure from gross haematuria due to glomerulonephritis:
      not only in IgA nephropathy and not associated with intratubular obstruction.
AB  - Seven patients with acute renal failure due to gross haematuria caused by
      glomerulonephritis are described. Gross haematuria lasting 4-40 days led to acute
      impairment of renal function of variable severity (peak plasma creatinine 1.3-12
      mg/dl) and duration. While partial recovery of renal function occurred in all
      patients within few days, complete remission was observed only some months later.
      Three patients had IgA nephropathy (2 the primary form and 1 nephritis secondary
      to Schonlein-Henoch purpura), two patients had acute postinfectious
      glomerulonephritis, and two others had focal necrotizing (pauci-immune)
      glomerulonephritis. The glomerular changes seen in the renal biopsy were not
      enough to explain per se the renal function impairment. Tubular changes, however,
      were severe and consisted of tubular necrosis, erythrocyte casts, erythrocyte
      phagocytosis by tubular cells, accompanied by interstitial damage (oedema, red
      cell extravasation, and inflammatory infiltrates). Study of the renal biopsies by
      immunofluorescence revealed no retrodiffusion of Tamm-Horsfall protein into the
      glomerular Bowman's space, a sign of obstructed tubular flow in any case. It is
      concluded that acute renal failure due to gross haematuria in glomerulonephritic
      patients may not occur only in IgA nephropathy, as reported so far, and is not
      associated with intratubular obstruction.

PMID- 7566574
TI  - Risks of acute renal failure after cardiopulmonary bypass surgery in children: a
      retrospective 10-year case-control study.
AB  - To our knowledge there are no case-control studies that have examined the main
      risk factors for acute renal failure (ARF) following cardiopulmonary bypass
      surgery in children. We therefore evaluated the potential risk factors in a large
      retrospective case-control study. Sixty-one of 2262 children (2.7%) developed
      postcardiopulmonary bypass surgery ARF requiring peritoneal dialysis (PD) from
      1982 to 1991. Fifty-eight of 61 cases (median age 8.5 months) were selected by
      systematic sampling and matched with 176 controls who did not develop ARF. The
      four matching variables were age, cardiopulmonary bypass and circulatory arrest
      duration, and year of operation. Mortality rate was 79% in cases (controls: 18%).
      Forty-three of 48 of the deceased cases did not recover renal function: no renal
      cause of death was found; 13 of 61 cases survived and recovered renal function.
      Multiple regression analysis showed the following significant risk factors for
      postcardiopulmonary bypass surgery ARF: central venous hypertension > 12 h (odds
      ratio (OR) 9.6); systolic arterial hypotension > 12 h (OR 8.9); dopamine dosage >
      15 micrograms/kg/min (OR 3.0); adrenaline (OR 5.9) and isoproterenol (OR 13.5)
      use. High preoperative serum creatinine, cyanosis, and vasodilator use were not
      significant risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566575
TI  - Myoinositol incorporation into lymphocytes of chronic renal failure patients is
      impaired.
AB  - Incorporation of myo-[2-3H]-inositol into peripheral blood mononuclear cells
      (PBMNC) and T-cell enriched lymphocytes was evaluated in in-vitro experiments in
      chronic renal failure (CRF) patients and healthy subjects. Incorporation of myo
      [2-3H]-inositol into the cells of CRF patients on conservative and haemodialysis
      treatment was found to be impaired in comparison with that observed in normal
      cells. Following PHA stimulation of the cells of CRF patients myo-[2-3H]-inositol
      incorporation decreased even further, while it increased in normal cells. Five
      hour haemodialysis session significantly depressed myoinositol incorporation into
      PBMNC, while its incorporation into T-cell enriched lymphocytes remained
      unaffected. Myoinositol incorporation into PBMNC and T-cell enriched lymphocytes
      was inhibited by prostaglandins and leukotrienes and was inversely related to the
      extent of pertussis toxinsensitive G protein activation. Reduced myoinositol
      incorporation into uraemic PHA-stimulated PBMNC may depend at least in part on
      their enhanced PGE2 and LTB4 release accompanied by increased intracellular cAMP
      production. In CRF impaired myoinositol incorporation into immune cells may prove
      the disarrangement in the early events of transmembrane signal transduction,
      which may share the responsibility for the cell-mediated immune defect in these
      patients.

PMID- 7566576
TI  - Influence of ACE inhibition on glucose tolerance in patients with stable chronic
      renal failure.
AB  - ACE inhibitors improve glucose tolerance and insulin sensitivity in hypertensive
      patients with normal renal function. Hypertensive patients with renal failure are
      a high-risk group who are particularly glucose intolerant and insulin resistant.
      We have therefore studied whether ACE inhibition improve glucose tolerance in
      this group as well. In a double-blind placebo-controlled crossover study 10
      patients with stable moderate chronic renal failure (mean endogenous creatinine
      clearance 40 +/- 16 ml/min/1.73 m2) were examined. Patients were randomly
      allocated to receive either placebo or the ACE inhibitor perindopril (2 mg/day
      per os) for 14 days. After 7 days of wash-out they received the alternative
      medications in random order for another 14 days. Before and after each of the two
      treatment periods (day 1 and day 15) an intravenous glucose tolerance test (i.v.
      GTT) with concomitant determination of insulin levels was performed. The glucose
      disappearance rate (K value) was calculated to express changes in glucose
      tolerance. An i.v. GTT was also performed in a group of healthy volunteers. The
      mean K value was significantly (P < 0.05) lower, i.e. glucose tolerance was
      impaired, in patients compared with healthy controls. In addition, baseline and
      peak insulin levels after the i.v. GTT were significantly higher (P < 0.05) in
      patients than in healthy subjects. The K values in patients before and after
      placebo treatment (1.33 +/- 0.31 and 1.41 +/- 0.45 respectively) were not
      significantly different from the values with perindopril treatment (1.35 +/- 0.37
      and 1.41 +/- 0.48 respectively). Furthermore, no significant differences between
      placebo and perindopril treatment were found with respect to the insulin response
      to the glucose load. The peak (5 min) insulin concentrations after the i.v.
      glucose load were 49.0 +/- 19.2 microU/ml (day 1) and 50.0 +/- 24.9 (day 15) with
      placebo and 49.2 +/- 19.3 (day 1) and 46.8 +/- 17.9 (day 15) with
      perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566578
TI  - Expression of fibrinogen receptors and GPIIb molecules on uraemic platelets:
      effect of recombinant human erythropoietin therapy.
AB  - In 14 chronic uraemic patients on regular haemodialysis treatment mean numbers of
      fibrinogen (Fg) receptors and glycoprotein IIb (GPIIb) molecules on one blood
      platelet were 8370 +/- 1282 and 15,694 +/- 2102 respectively, and they were
      significantly lowered in comparison with those found in 14 healthy persons
      (37,826 +/- 966 and 57,994 +/- 6824 respectively). A high positive correlation
      was found between numbers of GPIIb molecules and those of Fg receptors both in
      chronic uraemic patients and healthy subjects. Four-month treatment of
      haemodialysis patients with recombinant human erythropoietin (rHuEpo) induced
      significant rises in haematocrit from 22.3 +/- 1.2 to 31.2 +/- 1.7%, blood
      platelet count from 164,000 +/- 27,000/microliters to 206,000 +/-
      16,000/microliters and mean platelet volume from 7.08 +/- 0.29 fl to 8.26 +/-
      0.22 fl. However, in haemodialysis patients numbers of the investigated surface
      platelet receptors, measured at 8 and 16 week of rHuEpo treatment, remained
      unchanged.

PMID- 7566577
TI  - Effects of haemodialysis and continuous ambulatory peritoneal dialysis on the
      plasma clearance of an albumin-bound furan dicarboxylic acid.
AB  - Organic acids that are strongly bound to albumin are not removed by dialysis and
      the plasma concentrations of one such substance, a furan dicarboxylic acid (3
      carboxy-4-methyl-5-propyl-2-furanpropanoic acid: 5-propyl FPA) have been measured
      by HPLC in healthy subjects (n = 21), patients on regular haemodialysis (n = 30),
      and patients treated by continuous ambulatory peritoneal dialysis (n = 21). The
      mean (+/- SD) concentrations of 5-propyl FPA were significantly higher in
      haemodialysis (95 +/- 44 microM) compared to CAPD patients (28 +/- 19 microM) and
      both were higher than in healthy individuals (14 +/- 7 microM). Haemoglobin
      concentrations in CAPD patients were significantly higher than in those on
      haemodialysis while these patients had significantly higher albumin
      concentrations than CAPD patients. The concentration of 5-propyl FPA was
      positively correlated with the duration of dialysis for haemodialysis patients
      but not for CAPD patients. The lower concentrations of 5-propyl FPA in CAPD
      patients may at least partly explain the higher haemoglobin levels found in these
      patients.

PMID- 7566579
TI  - Immunological determination of advanced glycosylation end-products in human blood
      and urine.
AB  - Advanced glycosylation end-products (AGE) in human blood and urine were
      investigated with the aid of an AGE-specific enzyme-linked immunosorbent assay.
      Evidence is presented that AGE are natural constituents of human serum and urine.
      In diabetics with normal renal function only a small increase in serum AGE levels
      was found as compared to normal controls, while no difference in urinary
      excretion rate was discernible. Urinary excretion rate of AGE from diabetic and
      non-diabetic patients with end-stage renal disease was reduced, while high serum
      AGE levels were observed. AGE in serum occur in a low-molecular-weight fraction
      and in a possibly protein-bound high-molecular-weight fraction. In urine from
      normal controls three immunologically reactive fractions were detected whose
      apparent molecular mass ranged from 100 to 1000 Daltons, while in urine from
      patients with end-stage renal failure additional high-molecular-weight fractions
      appeared.

PMID- 7566580
TI  - Effect of the mode of calcitriol administration on PTH-ionized calcium
      relationship in uraemic patients with secondary hyperparathyroidism.
AB  - To assess the effect of the different modes of calcitriol administration on PTH
      ionized calcium relationship we conducted a prospective clinical trial in 33
      patients on chronic haemodialysis with secondary hyperparathyroidism (four times
      upper normal limit intact PTH) who were randomly assigned, with stratification to
      PTH levels, to receive daily oral, intermittent oral, or intermittent intravenous
      calcitriol at the same dose of 0.045 micrograms/kg/weekly. PTH-iCa curves were
      generated by inducing hypo- or hypercalcaemia in sequential haemodialysis 1 week
      apart, before and after 10 weeks on treatment. All patients were dialysed against
      a dialysate calcium concentration of 2.5 mEq/l throughout the study period. After
      drop-outs, 26 patients completed the study: 11 on intravenous calcitriol (mean
      basal PTH +/- SD: 666 +/- 280 pg/ml), eight on intermittent oral calcitriol (mean
      basal PTH: 831 +/- 361), and seven on daily oral calcitriol (mean basal PTH: 719
      +/- 280). Serum ionized calcium and phosphorus significantly increased in
      intravenous and daily oral groups after calcitriol treatment, but not in the
      intermittent oral group. Basal PTH did not significantly change in the three
      groups after 10 weeks on treatment. Maximal PTH significantly decreased in
      intravenous group (1449 +/- 660 versus 1122 +/- 691 pg/ml, P = 0.0085) and at the
      limit of statistical significance in the intermittent oral group (1701 +/- 774
      versus 1445 +/- 634, P = 0.12), but it did not change in the daily oral group.
      Minimal PTH did not modify in the three groups. In all three groups, a shift to
      the right in the PTH-iCa relationships were observed, with significant changes in
      the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566581
TI  - Correction by oral adsorbent of abnormal digestive tract milieu in rats with
      chronic renal failure.
AB  - In order to examine the mechanism by which the oral carbonaceous adsorbent, AST
      120 delays the appearance of glomerular sclerosis, experiments were carried out
      in 120 male Sprague-Dawley rats weighing 285-320 g. The rats were first subjected
      to 2/3, 3/4, and 4/5 nephrectomy (n = 40). The experiments were begun at 2 weeks
      after the surgery, and were performed over an 8-week period. Half of each group
      (n = 20) was administered 1 g/day of liquid AST-120, and the other half received
      liquid vehicle solution with pair feeding in each group. In the 2/3
      nephrectomized group the administration of AST-120 delayed the occurrence of
      glomerular hypertrophy and prevented the appearance of glomerular sclerosis
      without any significant differences in renal function, systemic blood pressure
      (SBP), and urinary protein excretion (U-P). In the 3/4 nephrectomized group the
      administration of AST-120 delayed the appearance of glomerular hypertrophy and
      sclerosis with significant decreases in SBP and U-P. In the 4/5 nephrectomized
      group the administration of AST-120 delayed the appearance of glomerular
      sclerosis and prevented a decrease in renal function. It is concluded that
      administration of the oral adsorbent AST-120 delays the occurrence of glomerular
      sclerosis by delaying the appearance of glomerular hypertrophy, systemic
      hypertension, and the increase in proteinuria. It can be therefore mentioned that
      the accumulating substances in the digestive tract worsen the abnormal milieu of
      chronic renal failure.

PMID- 7566582
TI  - Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis
      of CAPD patients: the role of mesothelial cells.
AB  - We compared peritoneal dialysis effluents from 18 CAPD patients who had not
      suffered from peritonitis during the last 6 months (group 1) with the effluents
      from five patients with acute peritonitis (group 2), measuring activation markers
      of coagulation and fibrinolysis. These markers included prothrombin fragment F1 +
      2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and
      fibrin degradation products (FbDP). In the dialysate of group 1 we found
      remarkably high levels of F1 + 2, TAT and FM concomitant with a high
      concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover.
      The balance between peritoneal generation and degradation of fibrin was disturbed
      in untreated patients of group 2, who had significantly higher levels of
      coagulation markers and a higher ratio between FM and FbDP. Seven days after
      treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2,
      TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial
      cells (MC) in the high peritoneal fibrin turnover we investigated the expression
      of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator
      (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in
      cultured human peritoneal MC under basal conditions and after exposure to tumour
      necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial
      lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent
      IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA
      production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566584
TI  - Chronic aortic dissection: presentation as acute renal failure.

PMID- 7566583
TI  - Patients' perception of health on renal replacement therapy: evaluation using a
      new instrument.
AB  - Patients' perception of their health is an important outcome measure in the
      management of chronic disease. Comparing that perception from patients receiving
      different forms of renal replacement therapy (RRT) with data from the general
      population could be used to monitor the effectiveness of treatment. The short
      form 36 (SF-36) questionnaire is a general measure of health status which has
      been validated in the UK and uses eight health scales comprising physical
      function, social function, role limitation (physical and emotional), mental
      health, energy, pain and overall health. Using the SF-36 questionnaire, the
      perception of health of patients receiving RRT was compared with data from
      healthy control subjects. One hundred and seventy-two of 185 (93%) patients
      receiving RRT--transplant (n = 102), haemodialysis (n = 43), and peritoneal
      dialysis (n = 27) completed the questionnaire; scores were compared with those
      from 542 healthy control subjects. The perception of health of haemodialysis and
      peritoneal dialysis patients was significantly worse than transplanted patients
      and controls in six of the eight scales (P < 0.05 dialysis versus transplant and
      controls). That of transplanted patients was worse in only two and better in one
      of the eight scales compared with the general population (P < 0.05). Patients
      were also stratified into low, medium, and high-risk groups based on age and
      comorbidity and were analysed irrespective of treatment modality. Scores were
      significantly different across the risk groups in five of the eight scales. We
      conclude that the SF-36 questionnaire is acceptable to patients on RRT and
      enables the perception of health of patients receiving RRT to be compared with
      that of the general population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566585
TI  - Reversible acute renal failure associated with Chlamydia pneumoniae infection.

PMID- 7566586
TI  - Significant elimination of bismuth by haemodialysis with a new heavy-metal
      chelating agent.

PMID- 7566587
TI  - Recurrent hemiparesis under amphotericin B for Candida albicans peritonitis.

PMID- 7566588
TI  - Bezafibrate induced reduction of renal function in a renal transplant recipient.

PMID- 7566589
TI  - Successful treatment of CMV-induced adrenal insufficiency by ganciclovir in a
      patient with the acquired immunodeficiency syndrome.

PMID- 7566590
TI  - A case of tuberculous peritonitis associated with abdominal-wall pseudocyst in a
      patient undergoing continuous ambulatory peritoneal dialysis (CAPD).

PMID- 7566591
TI  - Muckle-Wells syndrome nephropathy: lack of response to colchicine therapy.

PMID- 7566592
TI  - A child with recurrent urine infections and undescended testes.

PMID- 7566593
TI  - Is it justified to publish clinical observations based on traffic of transplanted
      organs.

PMID- 7566594
TI  - Evaluating the effect of desferrioxamine on bone-cell proliferation.

PMID- 7566595
TI  - Reduction of echinocytes post-haemodialysis.

PMID- 7566596
TI  - Normal pregnancy after renal transplantation.

PMID- 7566597
TI  - Nitric oxide--potential mediator in glomerulonephritis?

PMID- 7566598
TI  - Angiogenesis and vascular endothelial growth factor (VEGF): is it relevant in
      renal patients?

PMID- 7566599
TI  - The alpha-adducin polymorphism: a paradigm to analyse the genetics of primary
      hypertension.

PMID- 7566600
TI  - Lipoprotein(a) in renal disease: what we have, what we need, what we can forget.

PMID- 7566601
TI  - Glomerular disease in whites versus Australian aboriginals: 'last of a race in
      ruin' (G.K. Chesterton)

PMID- 7566602
TI  - Non-occlusive mesenteric infarction in dialysis patients: the importance of
      prevention and early intervention.

PMID- 7566603
TI  - Transplantation and the elderly.

PMID- 7566605
TI  - Platelet-derived growth factor in experimental glomerulonephritis.
AB  - Growth factors and in particular platelet-derived growth factor (PDGF) have been
      implicated in the pathogenesis of glomerulonephritis and glomerulosclerosis. We
      have studied the distribution of immunoreactive PDGF (iPDGF) within serial kidney
      biopsies (days 7, 15, 30, 90 and 120) of eight rats with an accelerated form of
      nephrotoxic serum nephritis (NTN). The course of NTN was mild in five rats and
      seere in three. Two patterns of immunostain for PDGF were noted. The first
      consisted of iPDGF-B chain in a glomerular segmental distribution similar to that
      of infiltrating monocytes (OX6+cells). At all stages of NTN the distribution of
      iPDGF-B chain correlated closely with the immunostain for monocytes. The second
      pattern of immunostain showed iPDGF-A chain in a diffuse distribution along the
      glomerular capillary lining and to a lesser extent in some mesangial cells. In
      severely affected rats the magnitude of the iPDGF-A increased along with
      glomerulosclerosis but disappeared later from areas of segmental and global
      glomerular obsolescence. By contrast, in rats with milder NTN glomerular iPDGF-A
      chain peaked early and decreased subsequently.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566604
TI  - Cytokines and growth factors in renal disease.

PMID- 7566606
TI  - Normal human polyspecific immunoglobulin G (intravenous immunoglobulin) modulates
      endothelial cell function in vitro.
AB  - We have analysed the in-vitro effect of pooled normal polyspecific immunoglobulin
      G (IVIg) and F(ab')2 fragments of IVIg on the secretion of prostacyclin (PGI2),
      thromboxane A2 (TxA2), and endothelin from cultured human umbilical vein
      endothelial cells. The stable metabolites, 6-keto-PGF1 alpha and TxB2, as well as
      endothelin, were measured by radioimmunoassay after extraction from the culture
      supernatants. IVIg inhibited TxB2 and endothelin secretion in a dose-dependent
      manner, but not that of 6-keto-PGF1 alpha. Therefore the ratio of 6-keto-PGF1
      alpha/TxB2 increased (+600%). The effect of F(ab')2 fragments prepared from IVIg
      was similar to that observed with IVIg, indicating that the effect of IVIg was
      mediated by the variable region of immunoglobulin. The results suggest that part
      of the effects of IVIg in inflammatory vasculitis may be due to a modification of
      the PGI2/TxA2 ratio and inhibition of endothelin secretion, and that natural IgG
      antibodies may participate in the homeostatic process of endothelium under
      physiological conditions.

PMID- 7566608
TI  - Evaluation of diagnostic criteria for analgesic nephropathy in patients with end
      stage renal failure: results of the ANNE study. Analgesic Nephropathy Network of
      Europe.
AB  - It was found that in Belgium, renal imaging techniques, demonstrating a decreased
      renal mass of both kidneys combined with either bumpy contours or papillary
      calcifications, were the only methods to reliably diagnose analgesic nephropathy
      (AN) in patients with end-stage renal failure. However, these criteria were
      selected in an area with a high prevalence of this disease (15.6% of the dialysis
      population at December 1990). To evaluate the criteria selected to diagnose AN in
      populations with lower or unknown prevalences of AN, the Analgesic Nephropathy
      Network of Europe (ANNE) was formed, consisting of 23 dialysis units from 14
      European countries and Brazil. During 1991-1992, 598 new patients with equivocal
      diagnosis of renal disease (excluding biopsy-proven glomerulonephritis,
      polycystic disease, diabetic nephropathy and other systemic diseases) and who
      began renal replacement therapy in the ANNE centres were evaluated by a short
      questionnaire and two renal imaging techniques: sonography and either tomography
      or computed tomography (CT) scan. A comparison of 82 abusers (daily use of
      analgesic mixtures for at least 5 years) and 495 controls corroborated the
      excellent diagnostic performance of the renal imaging techniques for AN. We
      recommend the use of these renal imaging criteria in all patients without a clear
      renal diagnosis in order to obtain a more reliable insight into the magnitude of
      the AN problem in different countries.

PMID- 7566607
TI  - Role of proteinases in renal hypertrophy and matrix accumulation.
AB  - Graded compensatory renal growth was induced either by unilateral (UNX) or 5/6
      nephrectomy (5/6-NX). Over the experimental period of 16 weeks, kidney weight
      increased by 59% in SHAM animals, while the remaining kidney in UNX rats more
      than doubled its initial weight. The hypertrophic response was most pronounced in
      the remnant kidney after 5/6-NX with a four fold increment in kidney weight.
      Morphologically glomerular volume increased moderately after UNX (+27%), while
      5/6-NX was associated with marked glomerular hypertrophy (+87%). Significant
      focal sclerosis was found in 11% of glomeruli in the remaining kidney after UNX.
      By contrast 83% of glomeruli wre sclerosed in the remnant kidney after 5/6-NX. In
      parallel, there was a significant increase in the glomerular protein/DNA ratio
      (+23%) in 5/6-NX but not in UNX animals. These glomerular alterations were
      associated with lower glomerular cysteine and metalloproteinase activities
      (collagenase, -57%; gelatinase, -49%) in 5/6-NX rats, while UNX rats had normal
      glomerular proteinase activities. In terms of tubular proteinases, cathepsin
      activities were significantly lower in UNX rats (cath. L+B, -38%; cath. B, -37%;
      cath. H, -27%) and more so after 5/6-nephrectomy (cath. L+B, -72%; cath. B, -73%;
      cath. H, -73%), while metalloproteinase activities were only reduced in 5/6-NX
      rats (collagenase, -35%; gelatinase, -58%). These findings demonstrate that
      kidney hypertrophy is associated with reduction in renal proteinase
      activities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566609
TI  - Recombinant human erythropoietin has no direct or strong vasoconstrictor effects
      in vivo and in vitro.
AB  - An elevation of blood pressure is observed in approximately 30% of dialysis
      patients treated with recombinant human erythropoietin (rHuEPO). Various studies
      have been performed in order to elucidate possible underlying mechanisms, but it
      is not yet well understood whether there is one major mechanism involved. In this
      present study, samples were obtained from male normotensive Wistar-Kyoto rats
      (WKY) and genetically hypertensive rats (SHR) at the age of 5 and 20 weeks.
      Thoracic aorta rings, with or without endothelium, isolated from WKY and SHR were
      used to evaluate the direct effect of rHuEPO on vascular smooth muscle by
      measuring the tension of vascular smooth muscle induced by various concentrations
      (1-100 IU/ml) of rHuEPO. Also, rHuEPO (10, 100, 1000 and 10,000 IU/kg) was
      intravenously administrated and the changes in mean blood pressure were recorded
      for 5-10 min. rHuEPO produced no significant contraction in the rat aortae in any
      of the preparation studies, in the presence or the absence of endothelium. The
      intravenous administration of rHuEPO had no immediate effect on mean blood
      pressure in 5- and 20-week-old WKY and SHR. These results suggest that the
      elevation of blood pressure observed in the clinical setting following the
      administration of rHuEPO is not due to a direct pressor effect on vascular smooth
      muscle.

PMID- 7566611
TI  - Effect of autonomic neuropathy on ventilatory response to progressive hypercapnia
      in dialysis patients.
AB  - The impact of autonomic neuropathy (common in patients on haemodialysis) on
      ventilatory response to hypercapnia has been studied. We investigated cardiac
      reflex tests in 20 patients on chronic haemodialysis (8 patients were found with
      and 12 without neuropathy of the autonomic nervous system). Using the hyperoxic
      CO2-rebreathing method (according to Read), we tested the above-mentioned two
      groups of patients and compared them with 14 healthy control subjects.
      Accumulation of CO2 in blood with hyperoxic CO2 rebreathing stimulates central
      chemoreceptors, and therefore causes a progressive rise in minute ventilation. In
      patients with autonomic neuropathy (n = 8), ventilatory response to increasing
      pCO2 was significantly lower than that in the controls (1.7 +/- 0.3 versus 3.2 +/
      0.5 l/min/mmHg, P < 0.001). On the other hand ventilatory response in patients
      without autonomic damage (n = 12) showed no significant difference when compared
      to controls (3.1 +/- 0.8 l/min/mmHg). There were no differences in lung function,
      arterial blood gas analysis, blood chemistry, duration on dialysis, and
      demographic data when comparing the patients with and those without autonomic
      damage. Our analysis shows different patterns of ventilatory response to
      increasing pCO2 in patients on haemodialysis. Autonomic neuropathy has to be
      considered when rebreathing tests are interpreted. The clinical relevance of
      these findings needs further investigation.

PMID- 7566610
TI  - Correction of chronic metabolic acidosis in haemodialysed patients by acetate
      free biofiltration does not influence parathyroid function.
AB  - In eight patients remaining acidotic after more than 1 year of bicarbonate
      haemodialysis, we studied the effect of correcting the chronic metabolic acidosis
      using acetate-free biofiltration for 4 months on the course of secondary
      hyperparathyroidism. An AN69 capillary membrane was employed with a bicarbonate
      infusion rate initially set at 1.8 l/h in all patients and then adjusted in each
      one to obtain a predialysis bicarbonate of > or = 23 mmol/l. Standard blood
      chemistry parameters were determined every 2 weeks. Measurements of PTH,
      calcifediol and calcitriol, as well as calcium-PTH curves were determined at the
      beginning and end of the study. While acetate-free biofiltration appears to be an
      adequate technique for the correction of chronic metabolic acidosis when
      bicarbonate dialysis fails, this study indicates that it does not influence
      secondary hyperparathyroidism in haemodialysed patients. The level of intact PTH
      did not vary significantly and the calcium-PTH curves at 0 and 4 months were
      superimposable with no significant differences in the set point and the slope of
      the curves.

PMID- 7566612
TI  - Interdialysis blood pressure control by long haemodialysis sessions.
AB  - High blood pressure (BP) is a major factor contributing to the high incidence of
      cardiovascular morbidity and mortality in haemodialysis (HD) patients. According
      to predialysis casual BP measurements, long HD has been shown to provide good BP
      control. To confirm this result during the period between dialysis sessions, we
      performed ambulatory monitoring of BP in 91 non-selected HD patients (mean age,
      58.7 (14.1) years; 14% incidence of nephrosclerosis and diabetes mellitus;
      treatment duration, 93.0 (77.2) months; 3 x 8 h/week, cuprophane, acetate buffer
      in 95% of the patients). Only one patient (1.1%) was receiving an
      antihypertensive medication. Ambulatory BP results were systolic (S) BP, 119.4
      (19.9) mmHg; diastolic (D) BP, 70.6 (12.9) mmHg; mean (M) BP, 87.6 (13.9) mmHg.
      These values were significantly lower than the casual predialysis BP data and
      close to the reference values reported by Staessen et al. in a meta-analysis
      including 3476 normotensive subjects. The MBP was inversely correlated with the
      treatment duration, but not with interdialysis weight gain. The MBP increased
      significantly in the last part of the interdialysis period, and this rise was not
      correlated with the interdialysis weight gain. The nocturnal/diurnal ratios for
      SBP and DBP for the HD patients (0.97 and 0.92) were higher than the reference
      values reported by Staessen, (0.87 and 0.83), and argued against a nocturnal
      decrease in BP. We found that 52.1% of the patients had an abnormal nocturnal BP
      fall (MBP fall < 5%). This feature worsened during the second night of the
      interdialysis period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566613
TI  - Transbrachial fine-needle arteriography with special focus on haemodialysis shunt
      imaging.
AB  - Retrospective analysis of the complication rate of transbrachial fine-needle
      arteriography was made to determine whether the advantages of arterial angiograms
      over venous fistulograms outweigh the possible complications. We included 236
      patients who had undergone 454 arterial fine-needle punctures with a 22-gauge
      cannula in the cubital fossa. Spasm as the only reliably detectable early
      complication of this retrospective study occurred with a frequency of 1.9% in
      dialysis patients. The only late and severe complication we found in reviewing
      217 arterial follow-up angiograms was one aneurysm. We consider arterial
      angiogram, using the fine-needle puncture technique, as a safe method for
      angiographic control of haemodialysis shunts. We attribute the low complication
      rate of less than 0.5% to the introduction of this technique.

PMID- 7566614
TI  - Evaluation of a high sodium-low potassium cold-storage solution by the isolated
      perfused rat kidney technique.
AB  - The isolated perfused rat kidney (IPK) model was used to assess initial renal
      function after 24 h preservation in 3 different cold storage solutions:
      EuroCollins (EC), a solution prepared according to the formulation of Belzer's
      solution (High-K+ UW) and a high Na(+)-low K+ Belzer UW solution (High-Na+ UW).
      GFR and FRNa were measured after 24 h cold storage in each of the solutions
      during 60 min, and were compared to values obtained in a control group in which
      renal function was measured immediately after the kidneys had been harvested. ATP
      and CP were measured in fresh renal tissue, in kidneys preserved for 24 h in each
      solution, in control IPK, and in reperfused IPK after they had been preserved for
      24 h. Main results showed that preservation in either solution caused a dramatic
      decrease in GFR and in FRNa within the first 60 min following reperfusion of cold
      stored kidneys. However FRNa was significantly higher in the High-Na+ UW group.
      ATP and CP content were decreased to approximately 10% of basal values in all
      experimental groups after cold-storage. Normothermic reperfusion of IPK after
      cold-storage induced a restoration of ATP levels, but CP content decreased
      further. There was no significant difference in ATP and CP content between cold
      storage solutions, nor any correlation between metabolic and functional
      parameters.

PMID- 7566615
TI  - Evaluation by histology, immunohistology and PCR of protocollized renal biopsies
      1 week post-transplant in relation to subsequent rejection episodes.
AB  - Renal biopsies were performed 1 week following renal transplantation at a time
      without clinical evidence of rejection in 43 patients (13 females, mean age 48
      years range 18-60 and 30 males, mean age 43 years range 17-59 years). Thirty-six
      biopsies were available for histological or immunohistochemical analysis.
      Immunohistochemical analyses were performed with monoclonal antibodies against
      leukocytes (CD45), monocytes (WT14), complement factor 3 (C3), T-cells (Leu4), T
      cell receptor alpha beta and gamma delta, tumour necrosis factor alpha (TNF
      alpha), IL-2 receptor (IL2-R, TAC), intercellular adhesion molecule-1 (ICAM1) and
      HLA-DR. The slides were scored semiquantitatively with the observers having no
      knowledge of clinical or patient data. TNF alpha and IL-2R were also measured by
      quantative PCR. None of the studied parameters correlated to delayed graft
      function or graft loss. Histological analysis showed that both focal interstitial
      infiltrate (18/35) and tubular basement membrane disruption (11/35) were followed
      by a higher incidence of subsequent rejection (P = 0.03 and 0.02 respectively).
      Also positivity for WT14 around tubuli (P = 0.02) was associated with subsequent
      occurrence of rejection. The intensity of staining of ICAM-1 on PTC as well as
      TAC on proximal tubular cells was associated with the number of subsequent
      rejection episodes. The association between the IL-2 receptor and subsequent
      rejection was also found applying PCR to the tissue specimens. We conclude that
      the presence of focal interstitial infiltrates and tubulitis in 1-week biopsies
      from well-functioning grafts carries an increased risk of subsequent
      rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566616
TI  - Survey of patient selection for cadaveric renal transplantation in the United
      Kingdom.
AB  - The limited supply of cadaveric kidneys results in failure to offer
      transplantation to all dialysis patients who might benefit. To survey current UK
      attitudes to selection for renal transplantation and to assess the influence on
      these attitudes of the shortage of cadaveric donor kidneys, a questionnaire
      including 20 case histories was circulated to 190 nephrologists and transplant
      surgeons involved in renal transplantation in the UK. The response rate was 79%.
      The acceptance rate of individual patients for renal transplantation varied from
      19 to 100% of respondents. Almost all patients were significantly (P < 0.05) more
      likely to be selected for transplantation if an adequate supply of kidneys were
      available. A correlation was noted between the responses from nephrologists
      working in Transplant Units and the percentages of their dialysis patients on
      transplant waiting lists (P < 0.01). This survey strongly suggests that more UK
      dialysis patients would be offered renal transplantation if the supply of
      cadaveric kidneys were adequate, and so the current national waiting list,
      although lengthy, understates the potential demand. Finally, this survey shows
      the wide variation that exists among both nephrologists and transplant surgeons
      in their attitude to patient selection for transplantation.

PMID- 7566617
TI  - Spectrum of hereditary renal disease in a kidney transplant population.
AB  - Re-evaluation of the underlying renal disease in 1000 consecutive kidney
      transplant patients revealed 129 cases of adult autosomal dominant polycystic
      kidney disease and 60 clear and seven suspected cases with other hereditary renal
      disorders. Twenty-four of 60 patients had cystic/dysplastic disease--10 of these
      classified as nephronophthisis, five as polycystic disease, and nine with the
      renal affection as part of a congenital malformation syndrome. Thirteen patients
      had Alport's syndrome, nine were diagnosed with tubulointerstitial nephritis, and
      six had an adult form of focal segmental glomerular sclerosis (FSGS). Two had
      changes classified as nephrosclerosis, but with an autosomal dominant mode of
      inheritance. Finnish type congenital nephrotic syndrome was present in two
      children and familial amyloidosis in two adults. Two patients had an unclassified
      disease. During follow-up, five patients with cystic/dysplastic disorders
      manifested liver disease. None of the patients with FSGS had recurrence and none
      of the Alport patients had anti-GBM disease. There were no other complications
      related to the renal condition. In conclusion, hereditary disorders are
      underestimated in regular registries of patients with end-stage renal failure. An
      adult form of FSGS and what seems to be a hereditary form of nephrosclerosis are
      among those that merit further study.

PMID- 7566618
TI  - Measurement of peritoneal fluid handling in children on continuous ambulatory
      peritoneal dialysis using dextran 70.
AB  - Fluid kinetics were studied in children treated with continuous ambulatory
      peritoneal dialysis (CAPD) aged between 2 and 15 years. Dextran 70 was used as a
      volume marker. A 4-h dwell was studied with a dwell volume of 40 mg/kg.
      Transcapillary ultrafiltration was measured as well as marker clearance, which is
      the best available approximation of lymphatic absorption in the clinical setting.
      In 11 children in whom dialysate was used containing 1.36% glucose transcapillary
      ultrafiltration was 250 +/- 79 ml/4 h/1.73 m2 and marker clearance 236 +/- 101
      ml/4 h/1.73 m2. In 13 children dialysed with 3.86% glucose, transcapillary
      ultrafiltration was 829 +/- 226 ml/4 h/1.73 m2 and marker clearance 307 +/- 176
      ml/4 h/1.73 m2. These values are similar to those found in adult patients. There
      was a positive correlation between age and transcapillary ultrafiltration in the
      group receiving dialysate containing 3.86% glucose (r = 0.69, P = 0.009). There
      was no correlation between age and marker clearance. It is concluded that fluid
      kinetics in children and adults on CAPD are similar when corrected for body
      surface area. In young children transcapillary ultrafiltration is lower, probably
      because dwell volume is low in relation to peritoneal surface area in these
      children.

PMID- 7566619
TI  - Effect of calcium-channel blocker on tumour necrosis factor alpha (TNF alpha)
      production in cyclosporin-treated renal transplant recipients.
AB  - PURPOSE OF THE STUDY: The influence of calcium-channel blocker treatment on in
      vitro TNF alpha production by peripheral blood mononuclear cells (PBMC) from
      renal transplant recipients treated with cyclosporin was studied. DESIGN: We
      compared spontaneous and OKT3-induced TNF alpha production of 12 renal transplant
      recipients treated with calcium-channel blocker therapy with that of 18 renal
      transplant recipients who were never treated with a calcium antagonist. RESULTS:
      The two groups were similar with regards to age, time after transplantation,
      dosage of immunosuppressive drugs, and blood cyclosporin levels. Spontaneous (481
      +/- 161 versus 319 +/- 74 pg/ml, n.s.) and OKT3-induced (745 +/- 182 versus 632
      +/- 112 pg/ml, n.s.) TNF alpha production were similar in both groups.
      CONCLUSIONS: The results indicate that in cyclosporin-treated renal transplant
      recipients calcium-channel blockers do not affect TNF alpha production.

PMID- 7566620
TI  - Monitoring of central venous dual-lumen catheter placement in haemodialysis:
      improvement of a technique for the practising nephrologist.
AB  - Mismanagement in the placement of central venous catheter (CVC) may occur in up
      to 20% of cases. The catheter can be inadvertently placed in the contralateral
      brachiocephalic vein, the ipsi or contralateral internal jugular vein, and
      usually a thoracic radiograph is necessary to evaluate its location. We propose a
      technique first described by Serafini et al. to establish the position of a CVC
      by endocavitary electrocardiography (EC-ECG) and its employment in a large number
      of uraemic patients requiring haemodialysis. This technique uses the tip of the
      CVC as reference lead in a standard electrocardiograph. The best employment of
      this technique has been obtained by echotomographic visualization of the internal
      jugular vein executed just before transcutaneous puncture of the vessel. For 13
      months we have successfully applied this technique in CVC placement in 81
      patients requiring haemodialysis. In our opinion this method is a safe and simple
      technique that avoids the need for thoracic radiographs and time lost waiting for
      radiographs that prolong the start of the haemodialysis session. According to our
      experience, we confirm that the EC-ECG technique provides a method for ensuring
      compliance with Food and Drug Administration guidelines regarding catheter tip
      location in uraemic patients.

PMID- 7566621
TI  - Relevance of the ulnaris fistula as a dialysis shunt.

PMID- 7566622
TI  - Reversible acute renal failure following aortic thrombosis inducing bilateral
      renal-artery occlusive disease.

PMID- 7566623
TI  - Reversible acute renal failure caused by the combined use of foscarnet and
      cyclosporin in organ transplanted patients.

PMID- 7566625
TI  - Glomerulocystic kidney disease associated with Wegener's granulomatosis and
      membranous glomerulonephritis: a case report.

PMID- 7566624
TI  - Activation of chronic hepatitis C virus infection by cyclophosphamide in a
      patient with cANCA-positive vasculitis.

PMID- 7566626
TI  - Glomerulonephritis associated with chronic granulomatous disease and systemic
      lupus erythematosus.

PMID- 7566627
TI  - Disseminated cryptococcosis in a lupus nephritis patient under long-term
      immunosuppression.

PMID- 7566628
TI  - Successful treatment of Kaposi's sarcoma in a renal allograft recipient.

PMID- 7566629
TI  - Non-invasive diagnosis of Fabry's disease by electronmicroscopic evaluation of
      urinary sediment.

PMID- 7566630
TI  - Urinary schistosomiasis.

PMID- 7566631
TI  - Lack of H-ATPase in distal nephron causing hypokalaemic distal RTA in a patient
      with Sjogren's syndrome.

PMID- 7566632
TI  - Infected intracardiac thrombi: complication of vascular access in haemodialysis
      patients.

PMID- 7566633
TI  - Stability of cyclosporin in blood upon shipping-related extended storage.

PMID- 7566634
TI  - Choice of dialysis membrane does not influence the outcome of residual renal
      function in haemodialysis patients.

PMID- 7566635
TI  - Influenza vaccination in renal patients.

PMID- 7566636
TI  - Investigation of tau-2 positive microglia-like cells in the subcortical nuclei of
      human neurodegenerative disorders.
AB  - An anti-tau monoclonal antibody tau-2 was demonstrated to react with the cells
      which characteristically appeared in the subcortical nuclei of certain
      neurodegenerative disorders. These cells had rod-like cell bodies and elongated
      processes, whose morphology was consistent with that of reactive microglia (tau-2
      positive microglia-like cells; TPMC). TPMC were diffusely scattered in the
      subcortical nuclei, especially the putamen, irrelevant to focal tissue injury
      such as infarcts and amyloid deposits. TPMC were positively immunostained with
      anti-ferritin antibody, but negatively with LN3, anti-GFAP, other kinds of anti
      tau and anti-neurofilament antibodies. TPMC were found in some cases of Alzheimer
      type dementia and diffuse Lewy body disease, but not in the cases of Parkinson's
      disease, Pick's disease and control without neurological disorder. Similar
      microglia-like cells were found around infarctic foci and amyloid cores of senile
      plaques, regardless of the disorder. They were, however, different from TPMC in
      that they were positively immunostained with LN3.

PMID- 7566637
TI  - Assembly of Alzheimer-like, insoluble filaments from brain cerebrosides.
AB  - Amphiphiles are molecules which contain a polar head and a hydrophobic tail. When
      the head contains a chiral center, amphiphiles, incubated in the presence of some
      di- and trivalent metal ions, have been shown to form large fibrous molecular
      aggregates. In this study, naturally occurring brain cerebroside was tested to
      determine if it had sufficient amphiphilic properties to form similar
      supramolecular structures. When galactocerebroside was heated in the presence of
      magnesium, it was able to form tubules, vesicles and filaments. The filaments
      included long fibrils that aggregated into dense bundles and short fibrils that
      were associated to form smaller bundles. These fibrils were shown to be resistant
      to solubilization in boiling SDS in the presence of reducing agents. This is the
      first report of a naturally occurring glycolipid being able to form filaments.
      Since their structural and physical properties are similar to the paired helical
      filaments of Alzheimer's disease, they may serve as an experimental model for
      their assembly.

PMID- 7566638
TI  - Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in
      brain cortex of rats.
AB  - A photochemical method using the Rose Bengal dye as thrombogenic agent was
      employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A
      transcerebral microdialysis probe was used to collect samples from ischemic
      cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within
      the first hour occurred. Neuropathological investigations demonstrate a
      reproducible damaged area surrounded by a thin peripheral area showing neuronal
      apoptotic phenomena. The method represents a reproducible model of focal cerebral
      ischemia with neuropathological aspects superimposable to those characteristic of
      thrombogenic stroke in man. This method could also be relevant in the study of
      neurotransmitters during the evolution of ischemia. Furthermore, the presence of
      apoptotic phenomena in the perilesional halo confirms an ischemic penumbra
      suggesting the significance of preclinical pharmacological trials.

PMID- 7566639
TI  - Visual neurons with higher selectivity can retain memory in the monkey temporal
      cortex.
AB  - Activities of individual neurons were recorded from the superior temporal sulcus
      (STS) of rhesus monkeys during the performance of a visual discrimination and
      memory task. Of 174 neurons analyzed in detail, 19 neurons showed sustained
      changes in discharge rates during the delay period (D neurons). All the D neurons
      showed responses during the presentation of the same stimulus and had higher
      selectivity compared to the remaining non-D neurons. The data indicated that a
      subgroup of highly selective visual neurons in the STS participate in short-term
      retention of these stimuli.

PMID- 7566640
TI  - Pharmacological characterization of alpha 2-adrenoceptor regulated serotonin
      release in the rat hippocampus.
AB  - The purpose of the present study was to confirm the functional regulation by
      alpha 2-adrenoceptors of the release of serotonin (5-HT) from the rat hippocampus
      in vivo. Under several pharmacological conditions, extracellular levels of 5-HT
      were estimated by assaying its concentrations in the perfusate by high
      performance liquid chromatography with electrochemical detection. Extracellular 5
      HT in the hippocampus was reduced by tetrodotoxin (10 microM) co-perfusion, but
      increased by perfusion of a selective 5-HT re-uptake inhibitor, fluoxetine (10
      microM). Addition of potassium (K+, 120 mM) to the perfusion fluid evoked an
      approximately 3-fold increase in 5-HT release. When the alpha 2-adrenoceptor
      agonist UK14,304 (0.1-10 microM) was added to the perfusion solution, the K(+)
      evoked 5-HT release was significantly inhibited in a concentration-dependent
      manner. This inhibitory action of UK14,304 was reversed by pretreatment with an
      alpha 2-adrenoceptor antagonist, idazoxan (5 mg/kg, i.p.). In rats which were
      catecholaminergically denervated with 6-hydroxydopamine, UK14,304 (10 microM)
      still inhibited the K(+)-evoked 5-HT release. Treatment with pertussis toxin
      (PTX) did not alter the K(+)-evoked release of 5-HT but abolished the inhibitory
      effect of UK14,304. These findings suggest that 5-HT release is functionally
      modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals
      in the rat hippocampus and furthermore, the possibility that the inhibitory of
      alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.

PMID- 7566641
TI  - Effects of the catechol-O-methyltransferase inhibitor tolcapone in Parkinson's
      disease: correlations between concentrations of dopaminergic substances in the
      plasma and cerebrospinal fluid and clinical improvement.
AB  - We compared the concentrations of dopaminergic substances in the plasma and
      cerebrospinal fluid (CSF) with clinical severity in patients with Parkinson's
      disease (PD) under L-dopa/carbidopa treatment and under L
      dopa/carbidopa+tolcapone treatment. Compared with treatment with L-dopa/carbidopa
      alone, the co-administration of tolcapone produced a significant decrease in
      clinical severity; a remarkable reduction in the 3-O-methyldopa (3-OMD)
      concentration and significant increase in the L-dopa concentration both in the
      plasma and CSF; and a significant increase in the dopamine concentration in the
      CSF. The clinical effects of tolcapone were closely correlated with the reduction
      in the 3-OMD concentration, but not with the increase in the dopamine and L-dopa
      concentrations in the CSF.

PMID- 7566642
TI  - Neurotrophin-3 is expressed in the posterior lobe of mouse cerebellum, but does
      not affect the cerebellar development.
AB  - We replaced the neurotrophin-3 (NT-3) gene with Escherichia coli-derived lacZ via
      homologous recombination in embryonic stem (ES) cells and generated the mutant
      mice. Here we show the in vivo expression of NT-3 in the cerebellum during the
      postnatal period. A high level of lacZ expression was found in the granular layer
      of posterior lobe (lobules VII to X) in the postnatal NT-3(+/-) cerebellum. The
      expression in these regions was reduced with age. Although the Purkinje cells are
      considered to be a target of NT-3 and the NT-3(-/-) mice displayed severe moving
      disorders like ataxia, no histological abnormality was observed in their
      cerebellum. These findings suggest that the NT-3 expressed in the cerebellum
      gives some trophic effects primarily to the posterior lobe, however, the
      deficiency does not affect its development.

PMID- 7566643
TI  - Intrathecal administration of endothelin-1 in the rat: impact on spinal cord
      blood flow and the blood-spinal cord barrier.
AB  - The purpose of this study was to examine the integrity of the blood-spinal cord
      barrier after intrathecal administration of endothelin-1 (ET-1) in the rat spinal
      cord. A laser Doppler probe was positioned in the exposed subarachnoid space at
      the T8 vertebral level. In the first experiment, horseradish peroxidase (HRP), a
      marker of barrier integrity, was given intravenously prior to the intrathecal
      application of ET-1. Blood flow was then recorded for 3 h, after which the
      anesthetized animals were euthanized. In the second experiment, animals exposed
      to endothelin were recovered after confirming a 50% reduction in blood flow. HRP
      was given 10 min prior to euthanasia at 24 h post infusion. The intensity of
      staining for HRP was quantified by optical density in fixed sections of spinal
      cord. There was a significant sustained reduction in spinal cord blood flow and
      significant barrier breakdown to HRP at both 3 and 24 h after administration of
      the peptide. Based upon these results we conclude that intrathecal infusion of ET
      1 reduces spinal cord blood flow and results in prolonged breakdown of the blood
      spinal cord barrier.

PMID- 7566644
TI  - Slow potential shifts preceding human focal paroxysmal discharges, as represented
      by spikes of benign rolandic epilepsy of childhood.
AB  - We examined the slow potential shifts preceding interictal spikes in the scalp
      EEGs of the children with benign rolandic epilepsy of childhood (BREC). In
      contrast to our expectations and the observations reported by Stodieck and Wieser
      (1987), we were not able to detect focal negative slow shifts preceding
      interictal discharges. Possible reasons for this result are as follows. The
      cerebral event to which we triggered might have been too 'weak'. Another problem
      is that not every single spike generated in the deep reaches the surface. Thus,
      the moment, a spike occurs in the scalp-recordings does not necessarily represent
      the moment the brain changes from one state to another. The reference electrode
      might also play a role in obscuring any slow shift.

PMID- 7566645
TI  - Adrenal medullary grafts suppress c-fos induction in spinal neurons of arthritic
      rats.
AB  - Expression of immediate-early genes such as c-fos is thought to reflect patterns
      of neuronal activity in the central nervous system. Prolonged increases in Fos
      protein-like-immunoreactivity (FOS-LI) are seen in the dorsal horn of adjuvant
      arthritic rats, and parallel increased pain behavior. Grafts of adrenal
      medullary, but not control tissue, into the spinal subarachnoid space reduce pain
      behavior and suppress the induction of spinal Fos-LI in arthritic rats. This
      reduction is particularly marked in superficial laminae (I-II), but is also
      significant in deeper laminae (III-IV and V-VI). The results of this study
      suggest that adrenal medullary transplants reduce spinal cord hyperactivation
      consequent to painful peripheral inflammation.

PMID- 7566646
TI  - Thapsigargin blocks long-term potentiation induced by weak, but not strong
      tetanisation in rat hippocampal CA1 neurons.
AB  - To elucidate the role of calcium release from internal stores during different
      paradigms of tetanisation in long-term potentiation (LTP), we have investigated
      the effects of thapsigargin on the elevation of the excitatory postsynaptic field
      potential (fEPSP) and the population spike (PS) after tetanisation. We found no
      effect on the duration of fEPSP potentiation if thapsigargin was perfused before
      strong (triple) tetanisation. However, the potentiation was reduced significantly
      from control experiments if thapsigargin was applied before weak (single)
      tetanisation. Surprisingly, we did not find any reduction of PS potentiation,
      which could be due to changes in the recurrent inhibition. We conclude that the
      involvement of internal calcium release in the mechanisms of LTP induction will
      be reduced if multiple tetanisation is used.

PMID- 7566647
TI  - Activity of area 5 neurons in monkeys during arm movements: effects of dentate
      nucleus lesion and motor cortex ablation.
AB  - Area 5 movement-related neurons were recorded in two trained monkeys respectively
      before and after (i) bilateral lesion of the dentate nucleus (DN), (ii) ablation
      of the motor cortex (area 4). DN lesion does not modify the proportion of early
      (command) and late (somaesthetic) neuronal changes. It does, however, increase
      both cellular and behavioural reaction times. The ablation of area 4 induces a
      clear-cut increase in the number of early neuronal changes during the period of
      recovery from arm palsy. These results show that: (i) the neocerebellum enhances
      the excitability of area 5 movement-related neurons; (ii) area 5 may compensate
      for the deficiency in area 4 by unmasking silent neurons and thereby subserves
      rehabilitation mechanisms.

PMID- 7566648
TI  - Amygdala N-methyl-D-aspartate receptors participate in the induction of long-term
      potentiation in the dentate gyrus in vivo.
AB  - We investigated the effects of injection of N-methyl-D-aspartate (NMDA) receptor
      antagonists, 2-amino-5-phosphonovalerate (APV) and 7-chlorokynurenate (7-Cl-Kyn),
      into the basolateral amygdala (BLA) on long-term potentiation (LTP) in the medial
      perforant path-dentate gyrus granule cell synapses of anesthetized rats.
      Injection of APV or 7-Cl-Kyn into the ipsilateral BLA did not affect the baseline
      synaptic responses, but significantly attenuated the dentate gyrus LTP induced by
      tetanic stimulation. Injection of APV into the contralateral BLA did not affect
      the induction of LTP. When APV was injected after tetanic stimulation, it did not
      affect the maintenance phase of LTP. These results suggest that NMDA receptors in
      the ipsilateral BLA partly participate in the induction of LTP in the dentate
      gyrus in vivo.

PMID- 7566649
TI  - Electrophysiological evidence for the antinociceptive effect of transcutaneous
      electrical stimulation on mechanically evoked responsiveness of dorsal horn
      neurons in neuropathic rats.
AB  - Using a rat model of peripheral neuropathy induced by a tight ligation of L5-6
      spinal nerves, the effects of transcutaneous electrical stimulation on the
      mechanical responses of wide dynamic range (WDR) dorsal horn neurons were
      investigated. The responses of the WDR neurons to both the brush and pinch
      stimuli were found to be enhanced in the neuropathic rats compared to those in
      the normal rats. These enhanced responses were depressed by low-frequency and
      high-intensity transcutaneous electrical stimulation (2 Hz, 4-5 mA) applied to
      the somatic receptive field. The durations of the depressive effects on the brush
      responses ranged between 30 and 45 min and those on the pinch responses were 60
      90 min. These results imply that the transcutaneous electrical stimulation used
      here produces an antinociceptive effect via a depressive action on the enhanced
      mechanical responsiveness of the spinal neurons in this rat model of peripheral
      neuropathy.

PMID- 7566650
TI  - A possible retinal information route to the circadian pacemaker through pretectal
      areas in the hagfish, Eptatretus burgeri.
AB  - By recording the locomotor activity rhythm of hagfish, Eptatretus burgeri, in
      which surgical lesions of the pretectal areas were made, we searched for the
      route of light information from the eyes to the circadian pacemaker, which is
      considered to be located in the preoptic nucleus. The entrainment of circadian
      activity rhythm to the light dark cycle, under 12 h light/12 h dark (12L:12D) was
      lost in animals whose pretectum was ablated with a pair of scissors and the
      animals then showed a free-running rhythm. Destruction of the pretectal areas
      with a high-frequency lesion generator also caused a free-running rhythm under
      12L:12D. These findings indicate that retinal information may entrain the
      circadian rhythm via the pretectal areas, which have retinofugal connections.

PMID- 7566651
TI  - Quantal secretion recorded from visualized boutons.
AB  - A method is described for recording the electrical signs of transmission at
      single boutons. Monopolar rat pelvic ganglion cells are electrically compact and
      receive an innervation from either single hypogastric or pelvic nerves that
      consists of a set of boutons which innervate the soma of the cells; each bouton
      possesses an active zone and can be observed with the confocal microscope after
      dextran-rhodamine orthograde labelling of the hypogastric nerves. Extracellular
      electrodes of about 8 microns diameter can be positioned in the loose-patch
      configuration over visualized boutons following their fluorescence with the vital
      dye, 3,3-diethyloxardicarbocyanine iodide (DiOC2(5)). Excitatory post-synaptic
      currents (EPSCs), due to stimulation of the hypogastric nerve, can be recorded
      from boutons in this way, provided that [Ca2+]o is lowered sufficiently to ensure
      failure of the initiation of the soma action potential by the EPSCs.

PMID- 7566652
TI  - ApoE3 binding to tau tandem repeat I is abolished by tau serine262
      phosphorylation.
AB  - The risk of Alzheimer's disease is determined, in part, by inheritance of
      specific alleles of ApoE. Isoform specific interactions of ApoE have been shown
      with the microtubule-associated protein tau, which forms the neurofibrillary
      tangle in this disease. Synthetic peptides representing each of the four
      microtubule-binding domains of tau more avidly bind ApoE3 than ApoE4.
      Phosphorylation of serine262 in domain I of tau decreases tau binding to
      microtubules and also abolishes binding by ApoE3. Understanding the molecular
      mechanisms of the high avidity, isoform-specific interactions of ApoE with tau
      may help in developing approaches for disease intervention.

PMID- 7566653
TI  - Decortication decreases paired-pulse facilitation in the neostriatal slice of the
      rat.
AB  - Paired-pulse facilitation, a form of short-term synaptic enhancement, occurs in
      the neostriatum. The present experiments were designed to determine the
      contributions of neostriatal afferents to the maintenance of this form of short
      term facilitation. There are 3 major afferents to the neostriatum: the neocortex,
      the substantia nigra and the medial thalamus. Since the largest inputs into the
      neostriatum emanate from the neocortex and substantia nigra, the effects of
      unilateral decortication or unilateral dopamine depletion on paired-pulse
      facilitation were primarily examined. Intracellular recordings were made from
      neostriatal neurons in brain slices 2 weeks following unilateral decortication or
      dopamine-depleting lesions. Statistically significant decreases in paired-pulse
      facilitation of the synaptic response evoked by local stimulation occurred only
      after neocortical damage. In contrast, paired-pulse facilitation in neostriatal
      neurons ipsilateral to the dopamine depleting lesion was not significantly
      altered. These results indicate that the corticostriatal input is primarily
      responsible for neostriatal short-term synaptic facilitation.

PMID- 7566654
TI  - Halothane prevents MK-801 neurotoxicity in the rat cingulate cortex.
AB  - Subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) antagonist, MK
      801, to adult rats causes a toxic vacuole reaction in neurons of the posterior
      cingulate cortex which is readily detected in histological sections 4 h following
      MK-801 administration. Certain drugs that facilitate neurotransmission at gamma
      aminobutyric acidA (GABAA) receptors block this neurotoxic action of MK-801. The
      anesthetic actions of halothane (fluothane) are thought to be due, at least in
      part, to an interaction with GABAA receptors. In the present study, we
      investigated the effect of halothane on MK-801 neurotoxicity. When halothane was
      administered for either 1 or 2 h, then terminated immediately prior to MK-801
      treatment, the vacuole reaction detected 4 h later was almost as severe as in
      controls not exposed to halothane. Administration of halothane for 1 h after MK
      801 injection postponed but did not prevent a relatively full vacuole reaction.
      However, when rats were kept under halothane anesthesia continuously throughout
      the 4 h period following MK-801 administration, the vacuole reaction was
      completely prevented. We postulate that halothane blocks MK-801 neurotoxicity by
      a facilitative action at GABAA receptors. Because halothane's duration of action
      is fleeting compared to the very long duration of action of MK-801, the efficacy
      of halothane in blocking MK-801 neurotoxicity varies in direct proportion to the
      length of time following MK-801 treatment that the rat brain is exposed to
      halothane.

PMID- 7566656
TI  - Nitric oxide producing neurons in the human colon: an immunohistochemical and
      histoenzymatical study.
AB  - The nitric oxide producing neurons of the human colonic myenteric plexus have
      been studied by using antibodies against cerebellar NO synthase type I (NOS-IR)
      and NADPH-diaphorase (NAPDH-d) histoenzymatic reaction. The majority of the
      stained neurons were both NOS-IR and NADPH-d-positive, while a few others were
      either NADPH-d-positive or NOS-IR only. Among the co-stained neurons, four
      subpopulations sharing various degrees of staining intensities have been
      identified. These findings indicate that in the human colon a one-to-one
      correlation between NOS-IR and NADPH-d positivity does not exist and thus the
      NADPH-d reaction does not delineate with certainty all NO-producing neurons. The
      degree of staining intensity might account for different intracellular amounts of
      these two enzymes.

PMID- 7566655
TI  - Central administration of cholecystokinin stimulates gastric pepsinogen secretion
      from anaesthetized rats.
AB  - Intracerebroventricular administration of CCK-8S was associated with a
      stimulation of gastric pepsinogen secretion from anaesthetized rats; similar
      effects were induced by CCK-8S given intravenously. The excitatory effect of
      intracerebroventricular CCK-8S was not modified by central injection of L-364,718
      or L-365,260, whereas both these antagonists, given by intravenous route,
      prevented the pepsigogue action of parenteral CCK-8S. Intracerebroventricular or
      intravenous CCK-8S also increased basal acid secretion, this latter effect being
      prevented by parenteral L-365,260 but not L-364,718. It is suggested that
      centrally applied CCK-8S evokes pepsinogen secretion through the activation of
      peripheral CCK-A and CCK-B receptors.

PMID- 7566657
TI  - Opioids acting on delta-receptors modulate Ca2+ currents in cultured
      postganglionic neurones of avian ciliary ganglia.
AB  - Opioid agonists inhibited Ba2+ currents in cultured postganglionic neurons of 3
      15-day-old embryonic avian ciliary ganglia. Leucine-enkephalin (LENK, 10-20
      microM) inhibited transient Ba2+ currents by 50% and sustained currents by 21%.
      The delta-opioid receptor agonist, DPDPE (0.02-10 microM), also inhibited Ba2+
      currents, but kappa- (U50488H) and mu- (DAMGO) receptor agonists had no effect.
      Inhibition of Ba2+ currents showed profound desensitisation during prolonged
      application of agonists, being reduced to approximately 25% of the original
      response after 4 min superfusion with leucine-enkephalin (10-20 microM).

PMID- 7566658
TI  - Immunocytochemical evidence for the presence of high levels of reduced
      glutathione in radial glial cells and horizontal cells in the rabbit retina.
AB  - Reduced glutathione is an antioxidant; it is thought to be essential for normal
      functioning of the central nervous system. We have examined by means of
      immunocytochemistry, the distribution of reduced glutathione in the retina of the
      rabbit. Strong immunoreactivity was present in the radial glial cells (Muller
      cells) and in the horizontal cells. Other neuronal elements contained only low,
      or no detectable levels of immunoreactivity for reduced glutathione. The presence
      of an abundance of reduced glutathione in glial cells suggests that glia play a
      critical role in regulating the content of potentially damaging oxidative species
      in the central nervous system.

PMID- 7566659
TI  - Decreased protein synthetic activity of the hypothalamic tuberomamillary nucleus
      in Alzheimer's disease as suggested by smaller Golgi apparatus.
AB  - The nucleus tuberalis lateralis (NTL) and tuberomamillary nucleus (TM), which are
      located close together in the tuberal region of the human hypothalamus, are
      differentially affected by Alzheimer's disease (AD), In the AD, the NTL shows
      only early cytoskeletal alterations, i.e. pre-tangle stages, while the TM is
      characterised by advanced Alzheimer's changes, e.g. neurofibrillary degeneration,
      senile plaques and amyloid deposition. Earlier we showed that the early
      cytoskeletal alterations in the NTL are not accompanied by changes in protein
      synthetic activity. The present study was carried out in order to measure the
      protein synthetic activity of the neighbouring area, the TM, which is severely
      affected by advanced Alzheimer changes. A polyclonal antibody against MG-160, a
      conserved membrane sialoglycoprotein of the Golgi apparatus, was used to stain
      this organelle and using an image analysis system, the size of the Golgi
      apparatus was measured as an index for synthetic and secretory activity in 15
      Alzheimer patients and 21 controls. A significant decrease in the size of the
      Golgi apparatus was found in the TM neurons in AD, although the cell profile area
      remained unchanged. These data suggest that the protein synthetic and secretory
      activity of TM neurons is indeed decreased in AD.

PMID- 7566660
TI  - Involvement of extracellular matrix in acetylcholine receptor epsilon-subunit
      gene expression at the rat neuromuscular junction.
AB  - During neuromuscular development, the nerve induces the expression of
      acetylcholine receptor (AChR) epsilon-subunit gene selectively in synaptic
      myonuclei. Here we show that even after elimination of neural effects by
      denervation, synaptic expression of epsilon-subunit transcripts is maintained for
      > 4 months. In contrast, after damage of the extracellular matrix (ECM) by
      treatment with proteolytic enzymes, epsilon-subunit mRNA is significantly reduced
      within less than 1 day, indicating a role of ECM in the regulation of AChR
      subunit transcripts at the synapse.

PMID- 7566661
TI  - N-methyl-D-aspartic acid-receptor antagonists block morphine-induced conditioned
      place preference in rats.
AB  - We addressed the question of whether (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine (MK-801) and DL-(E)-2-amino-4-methyl-5
      phosphono-3-pentenoic acid (CGP37849), a non-competitive and a competitive N
      methyl-D-aspartate (NMDA) receptor antagonist, respectively, are able to block
      morphine-induced conditioned place preference (CPP). MK-801 alone (0.1 mg/kg)
      produced neither a place preference nor a place aversion, but was able to
      completely block morphine-induced CPP. CGP37849 alone (10 mg/kg) produced a small
      but significant CPP, and was able to significantly attenuate morphine-induced
      CPP. These results cannot be due to simple additive effects of drug actions, but
      suggest that NMDA receptors play a complex role in the development of morphine
      CPP.

PMID- 7566662
TI  - Localization of noradrenaline transporter mRNA expression in the human locus
      coeruleus.
AB  - The distribution of the noradrenaline transporter mRNA was examined in the human
      dorsolateral pontine tegmentum, using in situ hybridization histochemistry with
      35S-labeled oligonucleotide probes. Analysis of film autoradiograms showed that
      noradrenaline transporter mRNA was expressed through the whole extent of the
      locus coeruleus complex. The largest population of labeled cells was seen in the
      nucleus locus coeruleus proper whereas few scattered labeled cells were
      visualized in its ventral subdivision, namely the locus subcoeruleus area. Thus,
      these anatomical findings suggest that cells expressing noradrenaline transporter
      mRNA in the human brainstem are predominantly, if not exclusively, concentrated
      within areas known to contain the largest collections of noradrenergic neurons.

PMID- 7566664
TI  - Seasonal variation in NPY immunoreactivity in the suprachiasmatic nucleus of the
      jerboa (Jaculus orientalis), a desert hibernator.
AB  - Using immunocytochemical techniques the seasonal variation in NPY immunoreactive
      fibers was investigated in the suprachiasmatic nucleus of both male and female
      jerboas. During the period of sexual quiescence (autumn), the amount of NPY
      immunoreactive fibers in the suprachiasmatic nucleus of both male and female
      jerboas was higher than in the period of sexual activity (spring-middle of
      summer). Compared with the respective control groups, castration during the
      period of sexual activity and testosterone or estrogen supplementation in
      sexually inactive animals did not affect NPY immunolabeling. These results
      indicate that the seasonal variation observed in NPY immunoreactivity in the
      suprachiasmatic nucleus of the jerboa is independent of circulating levels of
      steroid hormones. The possible influence of another hormonal system or a direct
      influence of an external factor such as photoperiod on NPY content in the
      suprachiasmatic nucleus remains to be determined.

PMID- 7566663
TI  - Extracellular glutamate levels in the hypothalamus and hippocampus of rats after
      acute or chronic oral intake of monosodium glutamate.
AB  - Using brain microdialysis we studied the effect of high doses of monosodium
      glutamate (MSG) on the extracellular concentration of glutamate in the
      hypothalamus and in the hippocampus of freely moving rats. MSG at 4 g/kg (40%
      solution) given by gavage caused a significant increase in plasma (5.3 +/- 0.4
      fold, P < 0.01) and extracellular glutamate in the hippocampus (4.2 +/- 0.6-fold,
      P < 0.01) and in the hypothalamus (8.9 +/- 1.7-fold, P < 0.01) compared to
      control rats receiving a 40% sucrose solution (10 ml/kg). The peak increase was
      found within 40 min after MSG administration then declining to baseline in the
      next 80 min. No changes were found in glutamate tissue concentrations. Twenty-one
      days after ad libitum MSG intake with the diet (approximately 4 g/kg) no changes
      were found, in plasma, in extracellular and tissue concentration of glutamate in
      the hypothalamus compared to rats fed with a normal diet. Glutamate release
      induced by 200 mM KCl was not modified as well. Histological analysis of Nissl
      stained brain tissue slices did not reveal any obvious cell loss in the
      hippocampus after acute or chronic MSG administration.

PMID- 7566665
TI  - Inactivation of a high conductance calcium dependent potassium current in rat
      hippocampal neurons.
AB  - Inactivating, high conductance BK-type currents have been recorded from inside
      out patches (internal and external K+ of 140 mM and 5 mM, respectively), obtained
      from cultured rat hippocampal neurons. The presence of prominent inactivation,
      not normally associated with BK channel activity, was dependent on two factors: a
      depolarizing step to 0 mV from a holding level of -80 mV and internal calcium at
      a concentration of 0.7 microM. Without the prior conditioning step to a negative
      potential, unitary currents were not evident at 0 mV; in addition, such currents
      were not elicited with the stimulus protocol if the internal Ca2+ was reduced to
      a level of 0.3 microM. Concomitant with current inactivation was the finding of a
      delayed activation of BK currents following the depolarizing step. Higher
      internal calcium, at 100 microM, led to persistent and sustained channel activity
      at 0 mV which was not dependent on a prior step to -80 mV. These results may be
      relevant to the complex nature of the repolarizing neuronal current Ic which is
      the macroscopic analogue of the unitary BK current.

PMID- 7566666
TI  - Involvement of free radicals in MPP+ neurotoxicity against rat dopaminergic
      neurons in culture.
AB  - To examine the mechanisms of the neurotoxicity of 1-methyl-4-phenylpyridinium
      (MPP+) against dopaminergic neurons, ventral mesencephalic cells from embryonic
      rats were cultured and exposed to MPP+ with various antioxidants or glutamate
      receptor antagonists to investigate the participation of free radicals and
      glutamate, respectively. Such antioxidants as vitamin E, vitamin C, coenzyme Q10,
      and catalase, but neither allopurinol nor superoxide dismutase, alleviated the
      MPP(+) -induced death of dopaminergic neurons, while glutamate receptor
      antagonists did not alter MPP+ neurotoxicity. These findings suggest the
      participation of free radicals, particularly hydroxyl radicals rather than
      superoxides, in the process of dopaminergic neuronal death evoked by MPP+.

PMID- 7566667
TI  - Noradrenaline effects on cultured rat sensory neurones exposed to morphine in
      utero or in vitro.
AB  - Dorsal root ganglion (DRG) neurones cultured from newborn rats were chronically
      exposed to 1 microM morphine. Untreated cells and in vitro morphine treated cells
      were cultured for 1 or 2 weeks from control offspring while in utero morphine
      treated cells were cultured for 1 week from offspring of morphine dependent rats.
      Noradrenaline (1 microM) was applied by pressure ejection. Intracellular
      recordings measured the change in action potential duration (APD). Noradrenaline
      significantly decreased the APD of 1-week-old untreated cells while the 2-week
      old untreated cells and the groups of morphine treated cells showed no
      significant change of APD following the drug application. Thus, newborn rat DRG
      neurones demonstrated a different sensitivity to noradrenaline with the culture
      duration or with morphine exposure.

PMID- 7566668
TI  - Odor responses after complete desensitization of the cAMP-dependent pathway in
      turtle olfactory cells.
AB  - The degree of contribution of the cAMP signal transduction pathway to odor
      responses was examined by recording current responses from isolated turtle
      olfactory cells under the whole-cell voltage clamp conditions. The cAMP signal
      transduction pathway was desensitized by dialyzing 1 mM cAMP and 0.5 mM IBMX from
      the patch pipette into the cells. Extracellular application of 3 mM cpt-cAMP, a
      membrane-permeable cAMP analogue elicited no response, indicating that the cAMP
      pathway was completely desensitized. Application of an odorant cocktail induced a
      large inward current under these conditions, suggesting that the cAMP-independent
      signal transduction contributes significantly to generation of odor responses in
      the turtle.

PMID- 7566669
TI  - Estimation of the interstitial free concentration of the putative dopamine D3
      receptor selective agonist 7-OH-DPAT in the dorsal striatum of freely moving
      rats.
AB  - Using the quantitative microdialysis 'point of no net flux' method, we estimated
      the interstitial free concentration (IFC) of (+/-)-7-hydroxy-2-(N,N-di-n
      propylamino)tetralin (7-OH-DPAT) in the dorsal striatum of freely moving rats
      after i.p. administration of the drug at the dose of 18.3 mumol/kg. The maximal
      IFC of 7-OH-DPAT was found to be 1.61 microM 20 min after the injection. Due to
      the approximately linear relationship between dose and dialysate concentration
      observed, it may be inferred that the behaviourally active 7-OH-DPAT dose of 0.12
      mumol/kg should give an IFC which does not exceed 10 nM. It is concluded that in
      vivo effects observed following 7-OH-DPAT i.p. administration at doses lower than
      0.12 mumol/kg might be considered as mediated by the dopamine D3 receptor.

PMID- 7566671
TI  - Repeated cocaine administration reduces 5-HT1A-mediated prolactin secretion in
      rats.
AB  - The prolactin and behavioral responses elicited by the 5-HT1A agonist 8-OH-DPAT
      (8-hydroxy-2-[di-n-propylamino]tetralin) were examined in male rats previously
      exposed to chronic cocaine (15 mg/kg, i.p., b.i.d., 7 days) or saline. After 42 h
      of withdrawal, cocaine-treated rats exhibited a reduced prolactin response to 8
      OH-DPAT challenge (50 micrograms/kg, i.v.). A 5-fold higher dose of 8-OH-DPAT
      stimulated maximal prolactin secretion that was similar in cocaine- and saline
      treated rats. Prior cocaine treatment had no effect on the 5-HT syndrome induced
      by 8-OH-DPAT. Our data agree with the findings of others and suggest that 5-HT1A
      receptors mediating neuroendocrine secretion become subsensitive after repeated
      cocaine administration.

PMID- 7566670
TI  - Effects of unilateral lesion of the nucleus basalis magnocellularis on carbachol-
      and serotonin-stimulated [3H]inositolmonophosphate accumulation in rat fronto
      parietal cortex.
AB  - We examined the effects of ibotenic acid induced unilateral lesion of the nucleus
      basalis magnocellularis (nBM) on carbachol- and serotonin-stimulated
      phosphoinositide (PI) breakdown in miniprisms obtained from rat fronto-parietal
      cortex 1 week following the lesion. Lesion-side muscarinic and serotoninergic
      receptor responsivity to agonist increased linearly relative to the severity of
      the nBM lesion as measured by choline acetyltransferase (ChAT) activity. These
      results provide further evidence for an interaction between central cholinergic
      and serotoninergic neurons.

PMID- 7566672
TI  - HIV initiatives.

PMID- 7566673
TI  - Review article: taking estrogens.
AB  - The advantages and disadvantages of hormone replacement are presented so that
      physicians will be better able to enlist the cooperation of their patients to
      achieve maximum benefit with minimum risk. The benefits of estrogen therapy
      clearly outweigh the possible side effects.

PMID- 7566674
TI  - Radiology/pathology conference from Robert Wood Johnson Medical School.
AB  - Inflammatory pseudotumor of the heart is a benign tumor-like lesion consisting of
      reparitive granulation tissue with fibroblasts, myofibroblasts, and plasma cells
      predominating. This lesion is commonly seen in the lungs. The authors present
      this case report to stimulate discussion.

PMID- 7566675
TI  - Case report: pyruvate kinase deficiency.
AB  - Pyruvate kinase deficiency is a rare cause of congenital hemolytic anemia.
      Despite a paucity of reports, splenectomy resulted in successful outcomes for two
      siblings with this disorder. The sisters were diagnosed at birth with profound
      jaundice and congenital nonspherocytic hemolytic anemia.

PMID- 7566676
TI  - The radiologic diagnosis of quadriceps tendon rupture.
AB  - This paper reviews the pathophysiological mechanism of quadriceps tendon rupture
      and its diagnosis by means of medical imaging including radiography, sonography,
      and magnetic resonance imaging (MRI). MRI findings are emphasized.

PMID- 7566677
TI  - Bronchial carcinoid tumors of the lung.
AB  - The bronchial carcinoid tumor is an uncommon primary pulmonary malignancy.
      Biologically, it is of neuroendocrine origin. Optimal treatment consists of
      resection of all tumor with conservation of pulmonary tissue. Ten consecutive
      resections of the bronchial carcinoid are reviewed.

PMID- 7566678
TI  - Medical history: Dr. Leonard Rowntree of Camden.
AB  - Rowntree began his career as a general practitioner in Camden in 1906. He
      published his first medical paper in 1908 in The Journal of the Medical Society
      of New Jersey and is best remembered for building the first dialysis apparatus in
      1914 and introducing the intravenous pyelogram in 1923.

PMID- 7566679
TI  - Tick bite victims and their environment: the risk of Lyme disease.
AB  - The authors surveyed 308 New Jersey tick bite victims. Education concerning
      landscape ecology, wildlife control, tick and wildlife habitat reduction, tick
      control using acaricides, and how to keep pets tick-free is especially needed to
      reduce human exposure to tick bites and Lyme disease.

PMID- 7566680
TI  - Time-course of trimethyltin effects on the monoaminergic systems of the rat
      brain.
AB  - The normalization of certain behavioral functions after a trimethyltin (TMT)
      insult indicates that compensatory processes may occur (Paule and McMillan, 1986;
      Bushnell and Angell, 1992). The monoamine (MA) neurons are known to be sensitive
      to TMT, however, a detailed temporal description of the effects is lacking. One
      week after TMT exposure, 8 mg/kg i.p. to adult male Sprague-Dawley rats, the
      levels of serotonin (5-HT) and noradrenaline (NA) were decreased in several brain
      regions, whereas the levels of dopamine were unaltered. In addition, a reduced
      density of 5-HT immunoreactive fibers was seen in hippocampus and cortex. The
      lesion in the serotonergic and noradrenergic systems was followed by a recovery.
      Twelve weeks after TMT treatment, 5-HT and NA levels were increased in
      hippocampus, and 5-HT levels in striatum. In cerebellum, NA, 5-HT and 5-HIAA
      levels were decreased at 12 weeks. Compensatory processes led to recovered levels
      of 5-HT and NA in all regions but cerebellum, although regionally specific
      increases developed with time possibly due to hyperinnervation. Inhibition of the
      aromatic amino acid decarboxylase with NSD1015 yields accumulation of
      catecholamine and 5-HT precursors. Two weeks after TMT, levels of 5-HTP and L
      dopa were not different in the TMT-treated rats as compared to controls,
      indicating that TMT does not affect MA synthesis.

PMID- 7566681
TI  - Effects of cyanide on the neural mechanisms controlling breathing in the neonatal
      rat in vitro.
AB  - The effects of hydrogen cyanide (HCN) on the neural mechanisms controlling
      breathing were studied. Two in vitro experimental models were utilized; the brain
      stem-spinal cord and the medullary slice preparations isolated from neonatal
      rats. Cyanide, at concentrations deemed lethal in vivo (50 microM), caused a
      modest (< 15%) depression of the frequency and amplitude of inspiratory rhythmic
      discharge when added to the bathing media. Moreover, the neuronal network
      underlying respiratory rhythmogenesis continued to function for hours in the
      presence of very high concentrations of cyanide (600 microM). We hypothesize that
      the rapid suppression of breathing caused by cyanide in vivo is due to changes in
      neuronal excitability in respiratory modulating populations in the CNS rather
      than due to perturbations of cellular oxidative metabolism or neurons within
      respiratory rhythm generating centres.

PMID- 7566682
TI  - Lindane blocks GABAA-mediated inhibition and modulates pyramidal cell
      excitability in the rat hippocampal slice.
AB  - An in vitro paired-pulse orthodromic stimulation technique was used to examine
      the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and
      recurrent collateral evoked inhibition in the rat hippocampal slice. This was
      done to establish simultaneous effects on a simple neural network and to develop
      procedures for more detailed analyses of the effects of lindane. Hippocampal
      slices 400 microns thick were perfused with oxygenated artificial cerebrospinal
      fluid. Electrodes were placed in the CA1 region to record extracellular
      population spike (PS) or excitatory postsynaptic potential (EPSP) responses to
      stimulation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobutyric
      acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse
      technique. Perfusion with lindane produced both time and dose dependent changes
      in a number of the responses measured. The most striking effect produced by
      lindane was the loss of GABAA-mediated recurrent collateral inhibition. This
      tended to occur rapidly, often before changes in EPSP or PS responses could be
      detected. With longer exposures to lindane, repetitive discharge of pyramidal
      cells developed resulting in multiple PSs to single stimuli. Lindane (50 microM)
      also completely reversed the effects of the injectable anesthetic, propofol, a
      compound known to potentiate GABAA-mediated inhibition via a direct action on the
      GABAA receptor-chloride channel complex. An analysis of input/output
      relationships at varying stimulus intensities showed that lindane increased EPSP
      and PS response amplitudes at any given stimulus intensity resulting in a
      leftward shift in the EPSP amplitude/stimulus intensity, PS amplitude/stimulus
      intensity and PS amplitude/EPSP amplitude relationships. This effect was most
      noticeable with low intensity stimuli and became progressively less so as
      stimulus intensities approached those yielding maximal responses. In addition
      lindane significantly increased paired pulse facilitation of EPSPs during paired
      stimulus presentation.

PMID- 7566683
TI  - Reactive gliosis induced by MK-801 in the rat posterior cingulate/retrosplenial
      cortex: GFAP evaluation by sandwich ELISA and immunocytochemistry.
AB  - MK-801 (dizocilpine maleate) and certain other related antagonists of the N
      methyl-D-aspartate receptor produce vacuolization and necrosis of neurons in the
      posterior cingulate/retrosplenial (PC/RS) cortex of rats. Neuronal necrosis
      initiates an astrocytic and microglial reaction. The present studies evaluated
      the astrocyte response with a sandwich format enzyme-linked immunosorbant assay
      (ELISA) for glial fibrillary acidic protein (GFAP), the major intermediate
      filament protein in astrocytes. In all cases, Sprague Dawley rats (age 60-70
      days) were given single subcutaneous doses of MK-801 and detergent-based sample
      homogenates were subjected to GFAP ELISA. Initially, female rats receiving
      vehicle or 0.1, 1.0, or 10 mg/kg MK-801 were sacrificed on 3, 5, 9, or 16 days
      postdose (DPD). Fresh brain samples included PC/RS (target) and frontal (non
      target) cortices. A significant, dose-dependent increase in GFAP occurred in the
      PC/RS cortex (highest in the 10 mg/kg group at 9 DPD). A second study with both
      sexes (10 mg/kg; 9 DPD) showed increased GFAP, but there was no difference by
      sex. Finally, punch samples from PC/RS, occipital, temporal, and entorhinal
      cortex (females; 10 mg/kg; 9 DPD) revealed a highly significant increase in GFAP
      confined to the PC/RS cortex. The localized increase in GFAP was confirmed by
      immunocytochemistry. These biochemical and immunocytochemical data demonstrate a
      localized astrocytic response to neuronal necrosis that is restricted to the
      PC/RS cortical target area. Our findings are consistent with previous data
      showing that chemical-induced injury of the CNS results in dose- and time
      dependent increases in GFAP that are restricted to the sites of damage.

PMID- 7566684
TI  - Potential efficacy and toxicity of GM1 ganglioside against trimethyltin-induced
      brain lesions in rats: comparison with protracted food restriction.
AB  - GM1 ganglioside (one week each at 10, 5, and 2.5 mg GM1/kg per day, ip) or
      gradual food restriction leading to a reduction in body weight to 75% of control
      were tested for their ability to block or reverse histopathologic and behavioral
      effects of trimethyltin (TMT) poisoning in rats. TMT (a single oral gavage of 6.0
      mg TMT HCI/kg body weight) reduced hippocampal weight, decreased hippocampal cell
      counts, decreased autoshaped learning measures, and suppressed progressive fixed
      ratio (PFR) lever pressing without affecting stable lever pressing. Neither GM1
      nor greater food restriction affected hippocampal weight. Greater food
      restriction prevented TMT's effects on autoshaping but not on PFR behavior, was
      without behavioral effects in animals not treated with TMT, and did not affect
      hippocampal histology. GM1 prevented certain TMT-induced decrements in
      autoshaping and PFR behavior but also suppressed autoshaping and stimulated
      stable fixed ratio behavior in animals not treated with TMT. GM1 also reduced
      hippocampal serotonin concentration, another "lesion-like" change. GM1 blocked
      TMT-induced hippocampal CA3b cell loss, but did not protect CA3c cells, the main
      locus of TMT hippocampal damage. The results support the idea that exogenous GM1
      is a potent neuroactive agent with complex actions in intact organisms,
      potentially beneficial and potentially toxic. Like GM1, food restriction induces
      complex and potentially beneficial effects, but it lacked GM1's biochemical and
      behavioral "side effects" (i.e. toxicity) in these experiments.

PMID- 7566685
TI  - Differential effects of ionizing radiation on the acquisition and performance of
      response sequences in rats.
AB  - To compare the effects of ionizing radiation on the acquisition and performance
      of response sequences, rats responding under a multiple schedule of food
      reinforcement were each administered 0.5-6 Gy of 60Co gamma radiation. In one
      component of the multiple schedule, subjects acquired a different three-response
      sequence each session by responding sequentially on one of three response keys in
      the presence of three consecutively presented colors (repeated acquisition). In
      the other component, the three-response sequence was the same each session
      (performance). The response sequence in each component was maintained by food
      presentation under a second-order fixed-ratio (FR) 2 schedule. Errors in both
      components produced a 5-sec timeout but did not reset the sequence. In all
      subjects, 0.5-6 Gy of gamma radiation dose-dependently decreased response rates
      in both components for 1-5 days postexposure. These gamma-ray doses also produced
      dose-dependent increases in errors in both components, but only at doses that
      substantially decreased response rate. Unlike the effects on response rate in
      both components, which were comparable over the 5-day period after exposure, the
      effects on accuracy were generally different for the two components. More
      specifically, the largest increases in percent errors in the performance
      component occurred on day 2 postexposure, whereas the largest increases in
      percent errors in the acquisition component occurred on day 4 postexposure. Taken
      together, these results indicate that (1) acute sublethal doses of gamma
      radiation differentially affect the acquisition and performance of response
      sequences, (2) these doses of gamma radiation differentially affect the measures
      of rate and accuracy within each condition of behavior, and (3) using a sensitive
      baseline, which includes an accuracy measure, provides important information
      about the disruptive effects of radiation that could not be predicted from the
      effects on response rate alone.

PMID- 7566686
TI  - Taurine in the olfactory system: effects of the olfactory toxicant dichlobenil.
AB  - Following intranasal instillation of 14C-taurine in C57B1/6 mice, there was a
      labelling of the olfactory neuroepithelium, axon bundles and axon layers in the
      olfactory bulb 4 and 24 h later, suggesting an axonal migration of radioactivity
      to the olfactory bulbs. In the olfactory bulbs the level of radioactivity was 45
      times higher than that in the posterior part of the brain. In mice treated with
      the olfactory toxicant dichlobenil, inducing necrosis in the dorsomedial
      olfactory region, there was a dose-dependent decrease in the level of 14C-taurine
      and 3H-carnosine (derived from the precursor 3H-beta-alanine) in the olfactory
      bulb. The migration of 14C-taurine in the olfactory system of dichlobenil-dosed
      mice gradually recovered 3 - 8 weeks later although an atypical epithelium
      remained in the dorsomedial portion of the olfactory region. The results suggest
      a transient reduction of the migration of taurine in the olfactory system of mice
      following chemically-induced toxicity at this site.

PMID- 7566687
TI  - In vitro effect of chlorpyrifos oxon on muscarinic receptors and adenylate
      cyclase.
AB  - Although the neurotoxicity of organophosphorus compounds is generally attributed
      to inhibition of acetylcholinesterase, recent reports have indicated that direct
      interactions with muscarinic receptors and signal transduction may be an
      additional mechanism of neurotoxicity. We have previously shown that the
      organophosphorus insecticide O,O-diethyl O-3,5,6-trichloro-2-pyridinyl
      phosphorothioate (chlorpyrifos) binds directly to muscarinic receptors and
      inhibits adenylate cyclase of rat striatum. We have further pursued those results
      in this study by investigating the effect of chlorpyrifos oxon in NG108-15
      neuroblastoma-glioma cells and Chinese hamster ovary cells transfected with cDNA
      for human m2 or m4 muscarinic receptor subtypes. At millimolar concentrations,
      chlorpyrifos oxon inhibited [3H]QNB binding in all cell lines. Likewise, [3H]CD
      binding was inhibited in NG108-15 and CHO-Hm2 cells. When the effect of
      chlorpyrifos oxon on adenylate cyclase was examined, the oxon was found to
      inhibit adenylate cyclase at millimolar concentrations. Though this effect on
      cyclase required greater concentrations of oxon than the comparable effect in
      striatal cells, it displayed the common characteristic of being atropine
      insensitive, suggesting that the effect on cyclase was not muscarinic receptor
      dependent. The inhibition of adenylate cyclase produced by chlorpyrifos oxon was
      not eliminated in pertussis toxin treated cells, lending further support to the
      idea that it is not a receptor-mediated event, and suggesting a potential direct
      interaction of chlorpyrifos oxon with the adenylate cyclase molecule.

PMID- 7566688
TI  - Quantitative evaluation of Al maltolate-induced neurodegeneration with subsequent
      Al removal by desferrioxamine treatment.
AB  - The intracisternal administration of aluminum maltolate to New Zealand white
      rabbits produces a reproducible neurofibrillary degeneration which is
      significantly reversed by desferrioxamine treatment. Quantitative analysis of
      brain and spinal cord tissue demonstrates that the aluminum deposition is higher
      close to the injection site than at locations further removed from the point of
      administration. Most importantly, treatment with desferrioxamine removes most of
      the aluminum from the brain and spinal cord, even from the sites of highest
      concentration. The ability to manipulate this system in the formation and
      degradation of NFD and in removal of aluminum may shed light on mechanisms of NFD
      formation and have implications for therapeutic advances in the treatment of
      certain human neurodegenerative diseases.

PMID- 7566689
TI  - Region-specific alterations in dopamine and serotonin metabolism in brains of
      rats exposed to low levels of lead.
AB  - Long-term exposure to low levels of lead (Pb) has been shown to produce
      behavioral disturbances in humans and animal models. Additionally, these
      disturbances have been shown to be associated with alterations in
      neurotransmitter systems in certain brain regions. The study presented here was
      undertaken to examine the effects of low level exposure to Pb on two
      neurotransmitter systems in various brain regions during the postweaning period.
      Exposure of twenty-one day old male Long-Evans rats to 0, 25, 50, or 500 ppm Pb
      (as lead acetate in drinking water) for 90 days resulted in mean blood Pb levels
      of 4, 13, 15 and 49 micrograms/dl respectively. Similarly, this exposure protocol
      produced dose-dependent increases in Pb contents of various regions of brain.
      Frontal cortex (FC), nucleus accumbens (NA), striatum (ST), hypothalamus (HY),
      hippocampus (HIP) and brainstem (BS) regions were analyzed for dopamine (DA),
      serotonin (5HT) and their metabolites. Measurements of DA in brain regions
      indicated that while DA contents of NA and HY were significantly reduced by the
      subchronic Pb exposure, its levels in FC and HIP were not affected by the low
      level exposures (25 and 50 ppm) to Pb, and were actually increased by exposure to
      500 ppm Pb. Dopamine metabolites, homovanillic acid (HVA) and 3,4
      dihydroxyphenylacetic acid (DOPAC) showed changes similar to DA. No significant
      changes in DA or its metabolites were observed in BS or ST in Pb-exposed animals.
      Serotonin content, on the other hand, showed consistent decreases in NA, FC, and
      BS in response to Pb with no changes in ST, HY, and HIP. Levels of the serotonin
      metabolite, 5-hydroxyindole acetic acid (5HIAA), were found to be decreased only
      in FC. These findings are of significance because the blood Pb values found at
      the two lower levels of Pb exposure (i.e., 25 and 50 ppm) were similar to those
      observed in children at risk for neurotoxicity (10-19 micrograms/dl).
      Additionally, these results suggest that the nucleus accumbens appears to be a
      preferentially susceptible area of the brain for Pb-induced neurotoxicity.

PMID- 7566691
TI  - Trimethyltin-induced neuropathy in the rat: interaction with thermoregulation.
AB  - The enhanced production of glial fibrillary acidic protein (GFAP) by astroglia
      appears to be a general response of the CNS to many types of toxic insult. The
      organometallic neurotoxicant, trimethyltin (TMT), is one such agent known to
      increase the production of GFAP as a consequence of widespread neuronal
      destruction. TMT also leads to transient reductions in body temperature (Tb), a
      response which may alter the neurotoxic effects of this compound. To study the
      role of Tb in the neurotoxic effects of TMT, rats were injected (i.v.) with
      saline or 8.0 mg/kg TMT and maintained at ambient temperatures (Ta) of 16, 22, or
      30 degrees C for 72 hr while Tb (core) was measured periodically. Animals were
      then housed at a Ta of 22 degrees C for 35 days after which time their brains
      were removed and dissected into hippocampus, cerebral cortex, striatum, midbrain
      and cerebellum for subsequent analysis of GFAP. TMT led to a significant decrease
      in Tb of rats housed at 22 degrees C measured 3 hr after treatment. Tb of rats
      maintained at Ta's of 16 and 30 degrees C was unaffected by TMT initially (i.e.,
      no hypothermia); however, by 72 hr after TMT, rats maintained at 22 and 30
      degrees C had a significantly elevated Tb. TMT led to marked elevations in GFAP
      levels, a response that was affected by Ta. In the hippocampus the elevation in
      GFAP was significantly greater in rats housed at 16 and 30 degrees C. A similar
      pattern was seen in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566690
TI  - In vitro and in vivo effects of lead on specific 3H-MK-801 binding to NMDA
      receptors in the brain of mice.
AB  - The in vitro and vivo effects of lead on the NMDA-receptors in adult and juvenile
      mice were studied by means of receptor binding assays. Adult female NMRI-mice
      received 100 and 1,000 ppm lead as nitrate in their drinking water for 30 and 90
      days. Perinatal exposure was achieved by treating gestating mice from the 5th day
      post conception with 0, 100 or 1,000 ppm lead in their drinking water.
      Characterization of the NMDA N-methyl-D-aspartate)-receptor was carried out ex
      vivo using binding studies on homogenates of the forebrain with the non
      competitive NMDA-antagonist 3H-MK-801. In vitro, complete inhibition of the
      radioligand binding was found with half maximal inhibiting concentrations (IC50
      values) of 19.7 +/- 2.6 microM (SEM) in absence of amino acids and 9.5 +/- 0.9 in
      presence of glutamate and glycine. These concentrations are in a range which
      could be achieved in vivo, e.g. the lead content in the forebrain of juvenile
      mice treated with 1,000 ppm lead was 10.0 +/- 1.8 mumol/kg wet weight. It was
      speculated that lead binds at the zinc binding site. In the presence of amino
      acids and divalent cations, such as calcium or magnesium, low lead concentrations
      lead to a significant increase in receptor affinity. Analysis of the saturation
      experiments carried out on forebrain homogenates of lead-treated animals showed a
      slight increase in receptor density of 13 or 15% with an unchanged Kd-value only
      in the adult animals treated with 100 ppm lead and in absence of stimulating
      amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566692
TI  - Uptake and subcellular distribution of 51Cr in Gomori-positive astrocytes in
      primary culture.
AB  - An unusual population of astrocytes containing Gomori-positive inclusions occurs
      in periventricular regions of the brain in all mammalian species. The inclusions
      are autofluorescent and exhibit non-enzymatic peroxidase activity. Estradiol
      treatment in vivo and cysteamine treatment in vitro have been shown to increase
      the number and size of these inclusions. Recent studies indicate that the Gomori
      inclusions are accumulations of autophagocytized abnormal mitochondria. The
      mitochondrial changes initiating Gomori inclusion formation begin with a loss of
      cristae. Energy dispersive X-ray microanalysis also reveals small emission peaks
      indicative of chromium. The appearance of chromium peaks in the initial stages of
      mitochondrial transformation suggests that enhanced permeability to chromium
      could play a causal role in generating Gomori inclusions. In the present study,
      we have examined the uptake and intracellular distribution of chromium during
      Gomori inclusion formation in cysteamine-treated cultured astrocytes. 51Cr was
      added to the media of glial cultures 24 hours prior to the initiation of the
      formation of Gomori inclusions by the addition of cysteamine. Cultures were fixed
      and prepared for EM radioautography at 12, 24, and 72 hours following the
      addition of cysteamine. 51Cr was added to control cells but they were not treated
      with cysteamine, and, they did not, therefore, develop Gomori inclusions.
      Cysteamine exposure resulted in a rapid sustained increase in radiolabel over the
      astrocytes. Much of the label was concentrated over mitochondria. At the late
      time points, label concentrated progressively over developing Gomori inclusions.
      These results confirm that the onset of Gomori inclusion formation coincides with
      increase cellular permeability to chromium and they indicate that uptake of
      chromium by mitochondria may play an important role in initiating development of
      these structures.

PMID- 7566693
TI  - Lead-induced changes in muscarinic cholinergic sensitivity.
AB  - This study was undertaken to determine whether the biochemical changes in
      cholinergic systems produced by lead exposure result in corresponding changes in
      cholinergic sensitivity in vivo. Rats chronically exposed from weaning to 0, 50
      or 150 ppm lead (Pb) acetate in drinking water were trained to discriminate the
      stimulus properties of a dose of 1.75 mg/kg of the muscarinic cholinergic
      agonist, arecoline, from saline, using standard operant food reinforced drug
      discrimination procedures. Following acquisition of the discrimination, various
      doses of arecoline, another muscarinic agonist, oxotremorine, a nicotinic
      agonist, nicotine, and the GABAA modulator, pentobarbital, were substituted for
      the arecoline training dose, and the ability of various doses of the muscarinic
      antagonist, atropine, to antagonize the discriminative stimulus properties of the
      1.75 mg/kg dose of arecoline were examined. Arecoline and oxotremorine produced
      dose-related increases in drug lever responding, while pentobarbital produced a
      partial generalization that was not dose-related. Arecoline's stimulus properties
      were substantially antagonized by atropine. Pb exposure significantly increased
      sensitivity to oxotremorine but not to arecoline, and attenuated the ability of
      some doses of atropine to antagonize the stimulus properties of arecoline. These
      findings demonstrate altered cholinergic sensitivity in response to
      environmentally relevant levels of lead in blood, and raise the possibility of
      cholinergic system disturbances in the behavioral manifestations produced by lead
      exposure.

PMID- 7566694
TI  - Glutathione S-transferases and gamma-glutamyl transpeptidase in the rat nervous
      systems: a basis for differential susceptibility to neurotoxicants.
AB  - Glutathione and its related enzymes play a major role in the detoxification of
      toxic chemicals. In rat brain the pattern of distribution of reduced glutathione
      exhibits cellular heterogeneity, suggesting also the possibility of cellular
      differences in glutathione conjugating capacity. To understand the potential role
      of GSH in detoxification of neurotoxicants, the distributions of the glutathione
      conjugating and metabolizing enzymes, glutathione S-transferase (GST; alpha-, mu-
      and pi-classes) and gamma-glutamyl transpeptidase (gamma-GT) were determined
      immunohistochemically in brain, lumbar spinal cord and dorsal root ganglia (DRG)
      of adult Sprague-Dawley rats using polyclonal antibodies. The influence of tissue
      fixation on apparent distribution was also examined. Glial cells and neurons
      throughout the nervous system were only weakly positive with alpha-GST in frozen
      sections. No immunoreactivity for the alpha-class GSTs was observed in any of the
      paraformaldehyde-fixed neural specimens examined. In microwave-fixed frozen
      sections, immunoreactivity to mu-GST was found in astrocytes and neurons
      throughout the brain and spinal cord, and in the neurons and satellite cells of
      the DRG. Immunoreactivity for pi-GST was seen in oligodendrocytes but not in
      astrocytes in any region of the CNS examined. Similarly, satellite cells of the
      DRG were positive for pi-GST. Neuronal perikarya of the entire neopallium,
      hippocampus, cerebellum, brainstem, spinal cord and DRG were also positively
      stained for pi-GST. The differential staining of astrocytes and oligodendrocytes
      with pi- and mu-GST was unaltered in paraformaldehyde fixed tissues, but the
      neuronal immunostaining was lost. The ependyma, pia and choroid plexus stained
      positively with all three GST antibodies regardless of fixation. Gamma-Glutamyl
      transpeptidase-like immunoreactivity was confined to non-neuronal elements of
      both central and peripheral nervous systems. Ependymal cells throughout the
      central nervous systems stained intensely with antibodies directed against gamma
      GT. Satellite and Schwann cells of the DRG and glial cells of the spinal cord and
      brain exhibited moderate to intense immunoreactivity for gamma-GT. The
      heterogeneous cellular distribution of glutathione and its metabolizing enzymes
      may reflect cellular differences in capacity for metabolic processing of both
      endogenous compound and xenobiotics.

PMID- 7566695
TI  - Defining neurotoxicity in a decision-making context.
AB  - Neurotoxicity is one of several noncancer endpoints used by regulatory agencies
      in risk assessment. At the US EPA, neurotoxicity is defined as an adverse change
      in the structure and/or function of the central and/or peripheral nervous system
      measured at the neurochemical, behavioral, neurophysiological or anatomical
      levels. Adverse effects include alterations that diminish an organism's ability
      to survive, reproduce or adapt to the environment. Generally, a weight-of
      evidence approach is used to evaluate observed effects. There is, for example, a
      high level of concern for persistent changes in the function or structure of the
      nervous system, while transient changes must be evaluated using further criteria.
      Compensatory changes resulting from cell death might represent activation of
      repair capacity and, since this could decrease future potential adaptability,
      reversibility is viewed with concern. In general, equal weight is given to
      chemicals that directly or indirectly affect the nervous system. Finally, effects
      on the nervous system must be compared to those on other organ systems to help
      rule out non-specific changes in neurobiological measures.

PMID- 7566697
TI  - Local injection of bicuculline into area 8 and area 6 of the rhesus monkey
      induces deficits in performance of a visual discrimination GO/NO-GO task.
AB  - While performing a symmetrically reinforced visual discrimination GO/NO-GO task,
      five monkeys were injected with a GABAA antagonist, bicuculline methiodide (BMI),
      into Brodmann's area 9, 8, 6, or 4. The task consisted of five periods: START,
      OFF, CUE, RESPONSE, and an inter-trial interval. The monkey was trained to make
      either the GO response (lever release) or the NO-GO response (continued pressing
      of the lever), depending on the color of the cue, during the RESPONSE period.
      Analysis was limited to 102 sites in which muscle convulsions of the forelimb
      and/or shoulder did not result from BMI injections. Errors in performance
      increased 10-60 min after injection into 10 of 33 sites in area 9, 9 of 25 sites
      in area 8, 20 of 34 sites in area 6, and 2 of 10 sites in area 4. The number of
      trials finished in a 120-min session decrease. Injections induced PRE-RESPONSE
      errors (release of the lever in either the OFF or CUE periods), GO RESPONSE
      errors (failure to release the lever when signaled), and NO-GO RESPONSE errors
      (release of the lever despite a signal not to release). The results suggest that
      both areas 8 and 6 are involved in correct performance of the GO/NO-GO task.

PMID- 7566696
TI  - Anatomy, development and lesion-induced plasticity of rodent corticospinal tract.
AB  - In this review the current knowledge of the anatomy, development and plasticity
      of the rodent corticospinal tract is summarised. Recent technical advancements,
      especially in neuronal tracing methods, have provided much new data concerning
      the anatomy of the corticospinal tract. The rodent corticospinal axons project to
      the subcortical nuclei via collateral branches. These collateral branches of
      corticospinal axons are formed by delayed interstitial budding during early
      postnatal periods. Corticospinal neurons are generated in the ventricular zone
      during a short time lag, migrate into the cortical plate, and settle in layer V
      of the cerebral cortex. The migration of corticospinal neurons is experimentally
      deranged by prenatal exposure to alcohol or genetically affected by the reeler
      genetic locus (rl), resulting in generation of ectopic corticospinal neurons.
      Such experimentally or genetically induced ectopic corticospinal neurons are a
      good model for examining whether target recognition and path finding are affected
      by the intracortical position of corticospinal neurons. Some chemical molecules
      (e.g. L1 and B-50/GAP43) are transiently expressed in the corticospinal tract
      during the perinatal period, while others (e.g. protein kinase C gamma subspecies
      and alpha CaM kinase II) are permanently expressed in the adult corticospinal
      tract. The only chemical marker specific for layer V corticofugal neurons is an
      antibody to a soluble protein, protein 35. Since the corticospinal tract in the
      rodent is an easily identified group of fibers situated in the most ventral
      portion of the dorsal funiculus of the spinal cord and exhibits considerable
      postnatal development, it has often been utilized in the neurological studies on
      plasticity and regenerative capacity of the lesioned central nervous system.
      Recently, it has been clarified that growing corticospinal fibers have the
      ability to penetrate and traverse across the lesion sites under certain special
      conditions.

PMID- 7566698
TI  - Neural connections of auditory association cortex with the posterior cingulate
      cortex in the monkey.
AB  - Clinical studies have indicated that the posterior cingulate cortex is intimately
      involved in verbal and auditory memory. The present study was performed to obtain
      anatomical evidence for the above proposal. The connections of the auditory
      cortical areas with the posterior cingulate cortex in the macaque monkey were
      examined by retrograde and anterograde tracing methods using wheat germ
      agglutinin-conjugated horseradish peroxidase (WGA-HRP). WGA-HRP was injected into
      either area TA, TB or TC in the superior temporal auditory cortex. Area TA was
      reciprocally connected with the posterior cingulate cortex, whereas areas TC and
      TB were not. The rostral two-thirds of area TA had major connections with the
      caudomedial lobule in the retrosplenial cortex (CML of Goldman-Rakic et al.,
      1984) and a minor one with area 23b. The caudal third of area tA was connected
      only with area 23b. However, neither labeled cells nor terminals were observed in
      areas 23a, 23c, 29, 30 or 31 in the posterior cingulate cortex following a WGA
      HRP injection into the caudal, intermediate or rostral portion of area TA. The
      present finding suggests that verbal and auditory memory impairment in patients
      with damage to the posterior cingulate cortex is largely due to damage to the CML
      and area 23b and not to the other posterior cingulate areas.

PMID- 7566699
TI  - Differential effects of aging on motoneurons and peripheral nerves innervating
      the hindlimb and forelimb muscles of rats.
AB  - We examined the number and size of ulnar (forelimb) and medial gastrocnemius (MG,
      hindlimb) motoneurons in middle-aged (9 months of age) and aged (27 months of
      age) male Fischer 344 rats. Morphological properties of the ulnar and the MG
      nerves were also studied. No significant difference was found in the mean number
      of the ulnar motoneurons between the two age groups, while that of MG motoneurons
      was significantly less in aged animals. A decrease in the number of myelinated
      fibers (including both afferent and efferent fibers) in the ulnar nerves was less
      than that in the MG nerves, although the age difference was not significant in
      either of the nerves. Soma atrophy of aged motoneurons was found in both MG and
      ulnar motor nuclei. The mean fascicular areas and myelinated fiber diameters were
      significantly increased in both the MG and the ulnar nerves in aged rats, but
      these were less pronounced for the ulnar nerve. The results indicate that most
      ulnar motoneurons, unlike MG motoneurons, survive at least to the age of 27
      months. Morphological changes in the peripheral nerves were also less for the
      ulnar nerve than for the MG nerve. Thus, we conclude that the effects of aging on
      motoneurons and peripheral nerves innervating MG muscle of the hindlimb are
      greater than those innervating forelimb muscles.

PMID- 7566700
TI  - Tau protein immunolocalization in fetal and adult human spinal cord.
AB  - In the present study, the monoclonal antibody Alz-50 has been used to determine
      and compare the immunohistochemical localization of phosphorylated tau proteins
      in the developing and normal adult spinal cord. At all stages of fetal life Alz
      50 fiber immunoreactivity was observed in the dorsal roots, in the dorsal and
      dorsolateral funiculi, and in restricted regions of the dorsal horn. Alz-50
      immunoreactivity was also demonstrated in the dorsal root ganglion neurons. In
      the adult spinal cord a consistent pattern of Alz-50 fiber immunoreactivity was
      localized in the superficial layers of the dorsal horn (lamina I and II) but not
      in dorsal and dorsolateral funiculi and in the dorsal root ganglion. Comparable
      results in fetal specimens have been obtained employing PHF-1, a monoclonal
      antibody generated against paired helical filament proteins from Alzheimer
      brains, while no significant immunostaining for PHF-1 was observed in the adult
      spinal cord. In addition, the staining with monoclonal and polyclonal anti-tau
      antibodies overlapped with that of Alz-50. The transient, selective pattern of
      Alz-50 and PHF-1 immunoreactivity may disclose some relevant functions of tau
      proteins during somatosensory pathway development.

PMID- 7566701
TI  - High-frequency stimulation of the basolateral amygdala facilitates the induction
      of long-term potentiation in the dentate gyrus in vivo.
AB  - We investigated the effect of high-frequency stimulation of the basolateral
      amygdala (BLA) on the induction of long-term potentiation (LTP) in the medial
      perforant path (PP)-dentate gyrus (DG) synapses of anesthetized rats. A
      conditioning stimulation (100 pulses at 100 Hz) of the ipsilateral BLA did not
      change the DG synaptic potential. However, when the BLA conditioning stimulation
      was applied at the same time as a weak tetanic stimulation of PP (20 pulses at 20
      Hz) which alone did not induce LTP, robust DG LTP was induced. Simultaneous
      application of contralateral BLA stimulation and PP weak tetanus did not induce
      LTP. Moreover, the ipsilateral BLA stimulation enhanced the magnitude of LTP
      induced by a moderate tetanic stimulation of PP (30 pulses at 60 Hz), but did not
      further enhance the LTP induced by a strong tetanic stimulation of PP (100 pulses
      at 100 Hz). These results suggest that the ipsilateral BLA neurons modulate the
      induction of DG LTP in vivo.

PMID- 7566702
TI  - Central mechanism of neural activation with cold acclimation of rats using Fos
      immunohistochemistry.
AB  - The expression of Fos protein in the rat diencephalon, brain stem, cerebellum,
      and spinal cord was investigated using immunohistochemistry during chronic cold
      exposure, in order to clarify the neural regions involved in the thermoregulatory
      responses and the central mechanism of neural activation with cold acclimation.
      Numerous Fos-positive cells were observed in many brain regions after cold
      exposure and changes in the number of Fos-positive cells were analyzed
      quantitatively. Fos-positive regions were classified into three groups on the
      basis of the expression period of Fos protein. The first group was where a
      significant number of Fos-positive cells were seen 3 h and 24 h after cold
      exposure, but not observed 14 days after exposure; the regions included the
      lateral septal nucleus (LS), parvocellular paraventricular hypothalamic nucleus
      (pPVN), posterior hypothalamic area (PH), supramammillary nucleus (SuM), locus
      coeruleus (LC), dorsal tegmental nucleus (DTg), vestibular nucleus (Ves), and
      nucleus of solitary tract (Sol). The second group was where a significant number
      of Fos-positive cells were found 3 h, 24 h and 14 days after cold exposure; the
      regions included the preoptic hypothalamic area (POA), paraventricular thalamic
      nucleus (PV), lateral preoptic area (LPO), zona incerta (ZI), subparafascicular
      thalamic nucleus (SPF), lateral dorsal central grey (CGLD), lateral ventral
      central grey (CGLV), microcellular tegmental nucleus (MiTg), lateral lemniscus
      nucleus (LL), dorsal parabrachial nucleus (DPB), and the cerebellum. The third
      group was where Fos-positive cells were more numerous 14 days after cold exposure
      than they were after 3 h and 24 h of exposure; these regions included the
      ventromedial hypothalamic nucleus (VMH) and the spinal cord. These results
      demonstrate that the numbers and regions of Fos-positive cells in the rat brains
      changed during chronic cold exposure, and such changes may reveal the cellular
      adaptation of the thermogenic responsive neurons in the rat brain to cold
      acclimation.

PMID- 7566703
TI  - In vitro positron emission tomography (PET): use of positron emission tracers in
      functional imaging in living brain slices.
AB  - Positron-emitting radionuclides have short half-lives and high radiation energies
      compared with radioisotopes generally used in biomedical research. We examined
      the possibility of applying positron emitter-labeled compounds to functional
      imaging in brain slices kept viable in an oxygenated buffer solution. Brain
      slices (300 microns thick) containing the striatum were incubated with positron
      emitter-labeled tracers for 30-45 min. The slices were then rinsed and placed on
      the bottom of a Plexiglas chamber filled with oxygenated Krebs-Ringer solution.
      The bottom of the chamber consisted of a thin polypropylene film to allow good
      penetration of beta+ particles from the brain slices. The chamber was placed on a
      storage phosphor screen, which has a higher sensitivity and a wider dynamic range
      than X-ray films. After an exposure period of 15-60 min, the screen was scanned
      by the analyzer and radioactivity images of brain slices were obtained within 20
      min. We succeeded in obtaining quantitative images of (1) [18F]fluorodeoxyglucose
      uptake, (2) dopamine D2 receptor binding, (3) dopa-decarboxylase activity, and
      (4) release of [11C]dopamine preloaded as L-[11C]DOPA in the brain slice
      preparation. These results demonstrate that positron emitter-labeled tracers in
      combination with storage phosphor screens are useful for functional imaging of
      living brain slices as a novel neuroscience technique.

PMID- 7566704
TI  - Semi-automatic data acquisition for quantitative neuroanatomy. MicroTrace-
      computer programme for recording of the spatial distribution of neuronal
      populations.
AB  - We present a computer programme, MicroTrace, designed for user-guided
      digitisation of objects in biological sections. The programme is optimised for
      recording the spatial distribution of neuronal structures, such as large
      populations of tracer-labelled cell bodies or axonal plexuses, regional borders,
      and surfaces. System requirements are a PC running Microsoft Windows, a
      microscope equipped with stepping motors, and a drawing tube. A computer
      generated drawing area, surrounded by menus and icons, is projected into the
      microscope field of view via the drawing tube. Different 'object' icons are
      assigned to individual object categories (cell types, surfaces, etc.).
      Digitisation is performed by pointing the cursor at objects in the section.
      Computer graphical symbols are superimposed on the digitised objects. All object
      categories are digitised, before moving the stage to other fields of view by
      manipulating the joystick or scroll bars. Movement of the microscope stage is
      accompanied by a translation of the graphical image, so that continuous feedback
      on the progress of the digitisation is provided. MicroTrace can readily be
      adapted to the specific needs of the user. We show its use in different
      experimental neuroanatomical techniques. Two-dimensional images and three
      dimensional reconstructions of neuronal distribution and surfaces are
      demonstrated.

PMID- 7566705
TI  - Motor speech centres in the frontal cortex.
AB  - Activities of the frontal cortices in both cerebral hemispheres preceding
      utterance of a short word were recorded and analyzed with multichannel SQUID
      gradiometers. Light stimuli of two different colours of 500 ms duration were
      delivered in front of a subject at random time intervals and in irregular order
      of the different colours. The subject should respond to either of the stimuli by
      uttering a short word, e.g., 'en' [en] ('round' in Japanese) or another by a
      short simple voice without meaning as a word, e.g., 'e' [e]. The initial sounds
      of both voices are to be the same, i.e., 'e' [e] in these examples. The 37
      gradiometers covering either the left or the right frontal-parietal part of the
      hemisphere recorded different magnetic fields between the word and the simple
      voice. Magnetic fields averaged 100 times at the onset of the stimuli revealed
      that the utterance of a word is preceded by significant magnetic field changes at
      a peak latency of 120-165 ms from the onset of light stimuli, whereas the
      utterance of a simple voice is not preceded by such changes. At a peak latency of
      160-190 ms, about 20-40 ms before the start of perioral EMGs, both the utterances
      are commonly preceded by magnetic field changes. Dipole fittings based on these
      magnetic fields suggest that the earlier magnetic fields reflect electrical
      activities in the ventral lateral part of the frontal association area, usually
      in both left and right hemispheres, and that the later fields represent those in
      the sensorimotor area in both the hemispheres. That part of the frontal
      association area appears to be the centre for organizing words to speak and to
      correspond possibly to the Broca's speech area.

PMID- 7566706
TI  - Managing nocturnal breakthrough pain.

PMID- 7566708
TI  - Myths & facts ... about physical restraints and the elderly.

PMID- 7566707
TI  - What you should know about sterilized equipment.

PMID- 7566709
TI  - Putting on sterile gloves.

PMID- 7566710
TI  - What caused this ventilator alarm?

PMID- 7566711
TI  - Selecting an NSAID for pain control.

PMID- 7566713
TI  - Getting the most out of patient-teaching videos.

PMID- 7566712
TI  - When depression hits home.

PMID- 7566714
TI  - How to handle a bomb threat.

PMID- 7566715
TI  - Getting patients off the readmission merry-go-round.

PMID- 7566716
TI  - Coping with a relative who has Alzheimer's.

PMID- 7566718
TI  - What the goldfish taught.

PMID- 7566717
TI  - Improving the process of elimination.

PMID- 7566719
TI  - Giving oral drugs safely.

PMID- 7566720
TI  - HELLP syndrome. Managing a pregnancy complication.

PMID- 7566721
TI  - Actionstat. Suspected child abuse.

PMID- 7566723
TI  - What was behind Ingebord's nonstop complaining?

PMID- 7566722
TI  - Caring for a patient with lung cancer.

PMID- 7566724
TI  - Home health care: staying safe in dangerous times.

PMID- 7566725
TI  - Coronary precautions: fact or fiction?

PMID- 7566726
TI  - Flawless phlebotomy: becoming a great collector.

PMID- 7566727
TI  - Comforting a child when someone close dies.

PMID- 7566728
TI  - Helping your patient follow his drug regimen.

PMID- 7566729
TI  - Heeding that "inner voice".

PMID- 7566730
TI  - Evaluating serum ferritin levels.

PMID- 7566731
TI  - Nina's last wink.

PMID- 7566732
TI  - Self-test. Treating a urinary tract infection.

PMID- 7566733
TI  - Monitoring blood loss--who's responsible?

PMID- 7566735
TI  - Practical tips on passing certification exams.

PMID- 7566734
TI  - Avoiding incomplete charting.

PMID- 7566736
TI  - Rekindling the flame.

PMID- 7566737
TI  - Photic information coded by vasoactive intestinal polypeptide and neuropeptide Y.
AB  - We investigated photic response of the concentration of vasoactive intestinal
      polypeptide (VIP) and neuropeptide Y in the rat suprachiasmatic nucleus (SCN) by
      enzyme immunoassay (EIA). The content of VIP in the SCN did not show circadian
      rhythms in constant darkness (DD). Under light-dark (LD) condition, VIP contents
      decreased over the course of the light period and then recovered during the dark
      period. When the light was continuously delivered to rats, VIP levels were
      monotonically decreased and did not return to the basal level. Accordingly, VIP
      in the SCN may code photic information on duration. On the other hand, there is a
      daily bimodal pattern in NPY content in the SCN under light-dark conditions. When
      rats were exposed to continuous light, the NPY level steadily increased and
      reached a peak in 2 h before returning to a basal level. The amount of increase
      did not depend on duration of light exposure. Thus, NPY in the SCN may code
      visual information on transitions, which is different from that conveyed by VIP.
      These results indicate that the two peptides act on a different stage of photic
      processing and may mediate distinct photic information to the circadian
      pacemaker.

PMID- 7566738
TI  - Effects of training, early handling, and perinatal flumazenil on shuttle box
      acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit.
AB  - The present series of studies investigated the effects of intensive training,
      postnatal handling-stimulation and/or perinatal flumazenil (Ro 15-1788,
      benzodiazepine receptor antagonist) on the acquisition of two-way active
      avoidance by Roman low-avoidance (RLA/Verh) rats. This rat line has been
      selectively bred for poor avoidance in the shuttle box, while their Roman high
      avoidance counterparts (RHA/Verh) have been selectively bred for their extremely
      good performance in that task. In the first experiment, RLA/Verh rats submitted
      to a long and intensive training procedure (unlike those submitted to short
      training) were able to achieve a performance of 56% of avoidances per session. In
      the second experiment both postnatal handling and perinatal flumazenil treatments
      increased avoidance responding in another group of RLA/Verh rats tested at the
      age of 18 months. Finally, in the last experiment, the performance of a third
      stock of RLA/Verh rats of the same age which had received perinatal flumazenil
      did not differ, on the later phases of training, from that shown by RHA/Verh
      animals. The results are discussed in terms of the "warm up" phenomena which
      seems to be highly involved in the selection of RLA/Verh rats, as well as on the
      possibility that central benzodiazepine receptors could play a role in the
      genetic deficit shown by RLA/Verh rats, which apparently confers a greater
      emotivity.

PMID- 7566741
TI  - Repeated acquisition of response sequences: the analysis of behavior in
      transition.
AB  - Repeated acquisition (RA) procedures are behavioral preparations in which
      subjects are required to learn new response sequences within each experimental
      session. Such procedures avoid problems inherent in nonRA learning procedures.
      For example, as the subject masters nonRA tasks, one begins to measure
      performance of a learned response rather than learning itself. Advantages to
      using RA procedures include (a) the strength of the within-subjects design,
      including the ability to establish dose effect curves within individual subjects;
      (b) the ability to assess learning phenomena over extended periods of time; (c)
      the ability to use chronic dosing regimens; and (d) the ability to assess
      treatments with permanent or long-lasting effects. In addition, analysis of the
      response patterns committed during acquisition allows for a description of how
      behavioral strategies may change in response to experimental manipulation.
      Difficulties include the relatively long training period often preceding
      attainment of a stable baseline of acquisition. This review examines the history
      of RA paradigms, with an emphasis on procedural comparisons.

PMID- 7566739
TI  - Testosterone-induced copulatory behavior is affected by the postcastration
      interval.
AB  - A well entrenched hypothesis regarding hormonal action is that as the time
      interval following hormonal deprivation increases there is a corresponding
      decrease in the sensitivity of the system to the effects of hormone replacement.
      With this in mind, we examined the effects of a prolonged period of hormonal
      deprivation (9 mo), and compared these to the effects of a shorter period (1
      month), on the restoration of copulatory behavior and seminal vesicle weights.
      Castration of sexually vigorous male Long-Evans rats at 6 mo of age was followed
      by the virtual disappearance of ejaculatory behavior within 1 mo. Testosterone
      (T) was administered (5 mm or 20 mm T-containing Silastic capsules) either 1 or 9
      mo after castration, and copulatory tests were conducted 3, 7, 10, 14, and 17
      days later. 5 mmT and 20 mmT were equally effective in restoring behavior in the
      rats treated 1 mo after castration. In contrast, 5 mmT was more effective in
      inducing copulatory behavior than 20 mmT in the rats treated 9 mo after
      castration. The time course to maximal effect was longer in the rats given T 9 mo
      after castration. Rats were sacrificed 21 days after T administration. Expressed
      seminal vesicle weights and plasma testosterone were increased in a dose
      dependent manner independent of the postcastration interval. These data indicate
      that somatic and behavioral effects of T are differentially modified by the
      period of preceding hormonal deprivation.

PMID- 7566740
TI  - Role of the serotonergic system in the forced swimming test.
AB  - The effect of manipulations aimed at modifying the function of the 5-HT system
      has been reviewed. 5-HT uptake inhibitors are devoid of any activity in rats and
      induce an anti-immobility effect in mice. The so-called 5-HT1A agonists reduce
      the immobility time with some differences in mice and rats, mice being less
      sensitive. None of the procedure aimed at reducing 5-HT function reduced
      immobility time. Therefore, the 5-HT system does not play a tonic role in animals
      performing the forced swimming test. The involvement of possible brain regions
      mediating the anti-immobility effects of 5-HT mimetic drugs has been discussed.

PMID- 7566742
TI  - Regulation of nutrient intake in humans: a theory based on taste and smell.
AB  - Oral and pharyngeal recognition of the chemical structure of physiologically
      relevant nutrients is proposed as a mechanism for regulating nutrient intake.
      Taste buds and olfactory receptors are proposed as the primary sites of
      recognition. Oral and pharyngeal sensory signals may be sufficient for producing
      satiation and termination of a meal provided the initiation of the meal is
      triggered by the body's need to replenish a deficient nutrient. A discussion of
      the impact of disturbances of normal regulation and some questions this model
      generates are also incorporated.

PMID- 7566743
TI  - Psychomotor functions in developing rats: ontogenetic approach to structure
      function relationships.
AB  - The functional development of the central nervous system (CNS) in the rat was
      studied from the 10th to the 45th postnatal day, through the ontogeny of
      psychomotor and sensory functions, by a battery of behavioral tests. The
      ontogenetic development of 10 different functions was described. The results
      showed that novelty-induced functions matured progressively in an adult-like
      pattern of functioning in the 3rd postnatal week. Indeed, exploratory activity
      was low at the 10th day, increased significantly to reach highest values from
      20th to 30th postnatal day, then declined at the 45th postnatal day. No
      habituation was exhibited by 10- and 15-day-old rats; it appeared at the age of
      20 days. Emotional reactivity induced by the novelty of surroundings clearly
      appeared from the 20th postnatal day, when the features of adult animal were
      reached. It appeared also that reflex and automatic motor functions came to
      maturity by the age of 3 wk, while voluntary motor functions continued to improve
      until the 30th day. Thus, the latency of the hind paw lifting reflex occurrence
      significantly decreased from the 10th to the 20th postnatal day, when the most
      improved values were reached. The wire-grasping times increased from the 10th to
      the 25th postnatal day in an exponential fashion. Locomotor activity developed
      significantly from the 10th to the 15th day, when the mature locomotion pattern
      was exhibited. The coordination of complex movements and motor initiative
      appeared only after the 20th postnatal day. The latencies of execution of
      crawling along the wire and of leap onto the ground decreased significantly from
      the 20th to the 45th day. These studies reveal the presence of the caudal to
      rostral sequence of CNS development, predicting a spatio-temporal functional
      maturation of nuclei and centers in the rat's CNS. The building of the time
      sequence of regional maturation of the brain integrated activities was attempted.

PMID- 7566744
TI  - The LHRH pulse generator: a mediobasal hypothalamic location.
AB  - The location and mechanism of LHRH pulse generator are discussed based on our
      series of experiments. Suckling stimulus is a novel stimulus that inhibits LH
      pulses without any cooperation from ovarian steroids, unlike other stimuli such
      as stress, photoperiod etc. It is directly involved in suppressing the activity
      of the LHRH pulse generator. The information from teats suckled by pups or babies
      is conveyed dorsally to the mediobasal hypothalamus (MBH), where the LHRH pulse
      generator may be located. Experiments using various types of deafferentation and
      fetal brain tissue transplantation confirmed that the LHRH pulse generator is
      located in the MBH and suggested that LHRH pulse generator consists of nonLHRH
      neurons. Endogenous excitatory amino acid is one of the possible
      neurotransmitters that regulate LHRH release at the nerve terminal in ME.

PMID- 7566745
TI  - Behaviour of zinc in physical exercise: a special reference to immunity and
      fatigue.
AB  - The variations in plasma zinc levels is dependent which follows intensivity of
      exercise. It is clear that there are short-term effects of exercise on zinc
      metabolism. It has also been shown that a high level of constant exercise can
      have long-term effects on zinc metabolism. It has been reported that runners have
      lower plasma zinc levels than controls. Long term endurance training has been
      shown to significantly decrease resting serum zinc levels in both male and female
      athletes compared to sedentary controls. Severe zinc deficiency can affect muscle
      function. One consequence of low serum zinc levels could be a reduction in muscle
      zinc concentrations. Since zinc is required for the activity of several enzymes
      in energy metabolism it could be predicted that low muscle zinc levels would
      result in a reduction in endurance capacity. Zinc may also be acting directly at
      membrane level; changes in extracellular zinc levels have been reported to
      influence twitch-tension relationship in muscle. Some investigators have
      associated acute and exhaustive exercise with decreased immune function. The
      mechanisms by which physical stress modulates immune competence are complex,
      involving both immune and neuroendocrine messengers. Muscular fatigue is of
      critical importance and as such it has been the subject matter of numerous
      investigators. Although many factors have been identified, a clear cause remains
      elusive. Factors discussed include: energy supply, the accumulation of
      metabolites, eccentric work, immune dysfunctions, etc. Recently we have
      demonstrated that daily high and maintained physical training over a prolonged
      period of time (7 mo) provokes marked modifications in the immune system of elite
      sportsmen accompanied by a psychological and biochemical stress level.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7566746
TI  - Neuronal activities underlying the electroencephalogram and evoked potentials of
      sleeping and waking: implications for information processing.
AB  - The low amplitude, high frequency waves of the electroencephalogram (EEG)
      indicative of wakefulness, are produced by a summation of potentials of
      thalamocortical neurons, which fire in a "tonic mode" of depolarization. In this
      mode, the transfer of information from the peripheral sense organs to the sensory
      cortex is facilitated, due to a tonic lowering of the discharge threshold of
      thalamocortical neurons. The transfer decreases during drowsiness when
      thalamocortical units are more hyperpolarized and have higher thresholds. In this
      state, neurons fire synchronously in a "burst mode," which is expressed in EEG
      spindling. During slow wave sleep sensory blocking reaches a maximum, when
      thalamocortical cells are yet more deeply hyperpolarized, although that what
      still passes to the cortex allows a shallow, subconscious, evaluation. The
      collective burst firing is more irregular, which results in large and slow EEG
      waves. In contrast, during rapid eye movement (REM) sleep the depolarized tonic
      mode of firing commonly associated with waking, is again reached. Similar to EEG
      patterns, the architecture of evoked potentials is dependent on the state of
      alertness. During waking, components in event related potentials (ERP) are
      moderate in amplitude, while during slow wave sleep larger waves are visible.
      This is caused by more synchronized unit responses with sharper phases of
      excitations and inhibitions, which results from increased hyperpolarizations. In
      contrast, visual ERPs belonging to REM sleep closely resemble those of
      wakefulness. In analyzing unit responses of thalamocortical neurons, it appeared
      that neuronal excitations are expressed in negative components of the ERP, while
      inhibitory neuronal activities are associated with positivity. Transient
      phenomena in the EEG, such as ERP waves, spindles and spike-wave discharges, are
      the expression of synaptic potentials in superficial cortical layers, where
      numerous synapses of afferent thalamocortical fibers are localized on the apical
      dendrites of deeper lying pyramidal neurons. It is suggested that the morphology
      of these EEG components is primarily due to the discharge characteristics of
      thalamocortical relay cells, whereby excitations underly negative waves and
      inhibitions positive waves. The notion of a general correspondence between
      thalamocortical neuronal activities and the polarity of transients in the
      cortical surface EEG, allows prudent speculations regarding components of ERPs.
      Two examples are given: the contingent negative variation (CNV) and the P300 of
      an ERP which can be elicited by an infrequent stimulus.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7566747
TI  - Neuroendocrine regulation of growth hormone secretion.
AB  - Growth hormone (GH) secretion is controlled by many factors, including stage of
      development, age, gonadal steroids, body composition, nutritional state, time of
      day and whether the subject is asleep or awake. Understanding regulation of GH
      secretion is important since this hormone regulates not only growth, but also the
      partitioning of nutrients and body composition. There is increasing evidence that
      there is a basic ultradian rhythm of GH secretion. The NSF Center studies will be
      facilitated by 3 major efforts: (a) improvement of sensitivity of GH assays to
      permit accurate description of GH pulses; (b) use of biomathematical models to
      objectively determine GH pulse characteristics, as well as calculation of
      secretion rates to facilitate the study of the relationship between neural
      controls and GH secretion; and (c) use of the tau mutant hamster and the new
      mouse mutant animal models. By manipulation of the endogenous circadian clock in
      these animal models it will be possible to study the relationship between
      endogenous circadian systems and ultradian GH rhythms.

PMID- 7566748
TI  - Control of motor and secretory functions of the stomach by a portal glucose
      signal.
AB  - D-glucose solution injected into the portal vein influences efferent tonic
      activities of the vagal nerve innervating the stomach. This suggested the
      existence of a neural connection between hepatic vagal branch afferents and
      gastric vagal efferents in the brain. Considering this observation together with
      findings indicating that electrical stimulation of the proximal cut end of the
      hepatic vagal branch changes acidity in the gastric perfusing fluid or pressure
      within the stomach, it has been presumed that hepatic afferent signals related to
      glucose may regulate the motor or secretory function of the stomach through a
      change in central nervous activity. Recently active interaction between the
      portal and medullary glucose signals in gastric function was discovered, and
      analysis of the characteristic features of the system is in progress.

PMID- 7566749
TI  - Effects of antidepressants on cognitive functions: a review.
AB  - The widespread use of antidepressants since the late 1950s and especially the
      ambulatory treatment of the majority of depressive patients raises the issue of
      the state of knowledge of the effects of these drugs on cognitive function. This
      review aims at synthesizing information about differential effects of
      antidepressants on cognitive function to facilitate good prescription. The first
      part of this review tries to summarize the main tasks used to explore global
      reactivity, attention, memory and psychomotor performances. The second part of
      this work presents the differential cognitive effects of antidepressants with a
      discrimination between substances which have a sedative impact, antidepressants
      with no cognitive effect, and drugs which seem to have a positive cognitive
      action. The differenciation is established for single and repeated
      administration, for healthy volunteers and depressed subjects. For each
      substance, the dose, the tasks selected and cognitive effect are discussed and
      the question of the real benefit of this cognitive impact is raised. The
      specificity of cognitive effects of antidepressants related to age and to the
      combination with alcohol are also tackled. Then the discussion raises the
      difficulty and the biases encountered to perform neuropsychological studies and
      particularly evaluation of cognitive effects of antidepressants. Finally the
      conclusion of this review gives some advice to select and prescribe
      antidepressants according to their cognitive effects.

PMID- 7566750
TI  - Anatomic basis of cognitive-emotional interactions in the primate prefrontal
      cortex.
AB  - Recognition that posterior basal and medial parts of the prefrontal cortex belong
      to the cortical component of the limbic system was important in understanding
      their anatomic and functional organization. In primates, the limbic system has
      evolved along with the neocortex and maintains strong connections with
      association areas. Consequently, damage to limbic structures in primates results
      in a series of deficits in cognitive, mnemonic and emotional processes. Limbic
      cortices differ in their structure and connections from the eulaminate areas.
      Limbic cortices issue widespread projections from their deep layers and reach
      eulaminate areas by terminating in layer I. By comparison, the eulaminate areas
      receive projections from a more restricted set of cortices and when they
      communicate with limbic cortices they issue projections from their upper layers
      and terminate in a columnar pattern. Several of the connectional and
      neurochemical characteristics of limbic cortices are observed as a transient
      feature in all areas during development. Anatomic evidence suggests that limbic
      areas retain some features observed in ontogeny, which may explain their great
      plasticity and involvement in learning and memory, but also their preferential
      vulnerability in several psychiatric and neurologic disorders.

PMID- 7566751
TI  - Fundamental neuroscience and the classification of psychiatric disorders.
AB  - Non-Darwinian views of evolution of nervous systems (e.g., Jacksonian evolution)
      conceive the present structure of the human brain as composed of a series of
      additive layers representing successive phylogenetic stages in evolution, layers
      which remain static after their emergence. In contrast to this view, recent
      allometric studies clearly show that limbic structures scale with the growth of
      the human brain (i.e., they do not remain stable but reach the size expected for
      the brain of a primate with the weight of a human brain). Data also show that
      limbic structures are significantly involved in cognitive functions such as
      memory and attention. Hence overlap of lesions in similar brain loci, especially
      in limbic regions, in both manic-depression and schizophrenia should come as no
      surprise. In the psychobiological sphere, the need for cognitive perceptual
      evaluation of the external world and internal state for emotional experience,
      further to the necessary visceral arousal, leads to a breakdown of the platonic,
      essentialist position, emotion vs. cognition at the psychological level, a
      problematic issue for the Kraepelinean view. Neural networks operation depend
      upon multiple nonlinear processes at the cellular, synaptic and network levels.
      Afferent input may serve not only to activate, but also to configure them into
      one of several circuit modes. These networks have been named polymorphic and can,
      at least to a measure, account for commonalities in lesion sites, in both
      affective and schizophrenic diseases. It is proposed that fundamental
      neuroscience should serve as one of the bases for the classification of
      psychiatric disorders.

PMID- 7566752
TI  - Smoking prevention.

PMID- 7566753
TI  - Oral health of Maori.

PMID- 7566754
TI  - Prelude.

PMID- 7566755
TI  - Health, education, and the virtues of efficiency.
AB  - Managerialism has been seen in recent times as an answer to problems which fall
      well outside the boundaries of commercial enterprise. This trend can be seen in
      both education at university level and health. But there are major risks in
      transporting the techniques and values of the market into domains which serve non
      commercial ends. Many of the most desired achievement of both health and
      education cannot be costed in monetary terms, and many of the activities that can
      be costed cannot produce profits. Education and health both have aims that are
      essentially moral, and the intrusion of managerialism undermines the morality and
      excuses departures from the central functions of both disciplines. This is not to
      say that efficiency and cost-cutting may not serve the good of education and
      health, but they cannot replace functions such as teaching, learning, and
      healing. There is a cogent argument for redefining the functions and structures
      of management in order to serve the knowledge workers whose role in health and
      education is indispensable, rather than to devolve increasing responsibility for
      management to them. The freedom of knowledge workers to practise their
      professions, to teach, to do research, and to reflect should be increased, rather
      than diminished progressively by institutional demands for more and more
      commitment the minutiae of management.

PMID- 7566756
TI  - Te mahi niho hauora ki Ratana Pa: the dental health project at Ratana Pa.
AB  - Following the success of a dental health project provided for Maori communities
      along the Wanganui River by the Royal New Zealand Dental Corps, the people of
      Ratana Pa, 20 km south of Wanganui, requested a similar service. Funding for a
      pilot project was provided by the Central Regional Health Authority through Good
      Health Wanganui. The project was a joint venture between the Health Committee of
      Ratana Pa and Dental Health of Good Health Wanganui. The dental health of the
      people at Ratana Pa was generally poor, featuring a high rate of decay and
      serious periodontal disease. Severe halitosis was common. As a result of poor
      oral health, many patients, especially young women, were whakama, a state of
      embarrassment and shame that caused them to keep their teeth hidden. An increase
      in self-esteem and greater interest in dental health occurred after treatment. A
      second treatment phase began in March 1995. This community-driven Maori health
      initiative, in partnership with a Regional Health Authority, fulfils obligations
      under the Treaty of Waitangi.

PMID- 7566758
TI  - Pancreatic transplantation: current status and implications for New Zealand.

PMID- 7566757
TI  - Prophylaxis against infective endocarditis in patients with cardiac disease.

PMID- 7566759
TI  - Variation in the time and day of onset of myocardial infarction and sudden death.
AB  - AIM: To examine circadian and weekly variation in the onset of acute myocardial
      infarction and sudden cardiac death. METHOD: A large population based coronary
      heart disease register, the ARCOS Study, which is collaborating in the WHO MONICA
      Project carried out in Auckland, New Zealand, 1983-90. There were 4983 patients
      aged 25-64 with definite myocardial infarction or coronary death. Main outcome
      measures--circadian and weekly variation in onset of symptoms of definite
      myocardial infarction and sudden cardiac death. RESULTS: Surviving patients
      showed a circadian pattern with a single morning peak in symptom onset (30.0%)
      while sudden death patients exhibited an afternoon peak (32.5%) and a secondary
      morning peak (27.6%). Within these two subgroups the circadian pattern was
      analysed by various risk factors and medications. A weekly variation was found
      with an increased incidence of onset of symptoms during the weekend and on Monday
      for surviving patients and a Saturday high (18.6%) for sudden death patients.
      CONCLUSIONS: Further investigation of physiological changes within subgroups
      during the key periods may provide insight into triggering mechanisms and lead to
      better means for prevention.

PMID- 7566760
TI  - Testicular cancer in fire fighters: a cluster investigation.
AB  - AIM: To investigate an apparent cluster of four testicular cancer cases in
      Wellington fire fighters with a view to determining whether there was a common
      causal factor, and whether the cluster was indicative of an occupational risk for
      fire fighters generally. METHOD: Subjects were interviewed about possible risk
      factors and occupational histories using a structured questionnaire; medical
      records were reviewed, and diagnoses were verified from the original histological
      slides. Data on testicular cancer in fire fighters were obtained from the New
      Zealand cancer registry. Standardised incidence ratios were calculated to assess
      the likelihood that the cluster had arisen by chance. RESULTS: All four cancers
      were verified as germ cell testicular cancers. No common risk factors were
      apparent from the review of the medical records or from the questionnaire
      interviews. The only testicular cancers known to have occurred in Wellington fire
      fighters in the 1980s were the four investigated in this study. Only two of the
      four cases investigated were registered with the New Zealand cancer registry. The
      relative risk estimate for Wellington fire fighters for the period 1980-91 was
      8.2, with an approximate 95% confidence interval of 2.2-21 (p = 0.002).
      CONCLUSION: There was an unusually high risk of testicular cancer in Wellington
      fire fighters in the 1980s, with no obvious explanations, although chance could
      not be excluded. Whether this high risk continues in the 1990s would require a
      separate investigation. At present the weight of evidence does not indicate that
      fire fighters in other areas of New Zealand also experienced an elevated
      testicular cancer incidence rate.

PMID- 7566761
TI  - Vitamin K administration in neonates: survey of compliance with recommended
      practices in the Dunedin area.
AB  - AIMS: A three dose oral regimen for vitamin K prophylaxis was introduced as an
      alternative to a single intramuscular injection in August 1992. An assessment of
      the acceptance of this regimen was needed to determine if the risk of developing
      haemorrhagic disease of the newborn had altered. METHODS: A survey of compliance
      with the recommendations was made using a telephone questionnaire to 179 parents.
      RESULTS: One hundred and fifty three breast fed infants received oral vitamin K.
      Repeated doses were given to 133 (97%) of 138 breast fed infants at 1 week and
      115 (94%) of 122 breast fed infants at 6 weeks. Twenty three of the infants were
      given the third dose of vitamin K later than recommended. CONCLUSION: Although
      the majority of infants received all three recommended doses, a quarter of
      infants given oral prophylaxis are at an increased risk of haemorrhagic disease
      of the newborn in our sample population.

PMID- 7566762
TI  - Clinical audit and standardised follow up improve quality of documentation in
      diabetes care.
AB  - AIM: High quality of follow up data is important in improving diabetes care. Our
      aim was to improve quality of documentation and diabetes care by using a
      combination of clinical audit and standardised follow up. METHODS: During 2
      months in 1991-2 the records of all patients attending the diabetes clinic were
      reviewed. Quality of documentation was assessed for diabetic medication,
      hypoglycaemia, glycoprotein level, body weight, smoking history, blood pressure,
      albuminuria, visual acuity, fundi examination, neuropathy, foot inspection,
      peripheral vascular disease, cerebrovascular disease, ischaemic heart disease and
      serum cholesterol. For all parameters results and documented interventions were
      noted. A standardised follow up form was then introduced and the audit was
      repeated in 1993-4. RESULTS: 156 patients were included in 1991-2 and 138 in 1993
      4. There were no differences between the two groups with regards to baseline
      demographic data. Follow up data for 10 parameters were between 1.15 and 5.35
      times more likely to have been recorded in 1993-4. The other 5 items were as
      likely to have been recorded in 1991-2 as in 1993-4. However, the differences
      between the two audits were less convincing and inconsistent for number of
      abnormalities detected in each group and whether abnormal results led to
      documented actions. CONCLUSIONS: These results show that repeated audit and
      standardised follow up can improve the quality of documentation of diabetic
      follow up, but that this does not necessarily mean that a higher proportion of
      abnormal results will be detected and acted upon. Additional practice protocols
      may be necessary to achieve this.

PMID- 7566763
TI  - The incidence of hyperemesis gravidarum is increased among Pacific Islanders
      living in Wellington.
AB  - AIMS: To compare the incidence of hyperemesis gravidarum among Pacific Islanders
      living in Wellington with nonPacific Islanders and to investigate some properties
      of the disorder. METHODS: Data were collected on all first time admissions to
      Wellington Women's Hospital for hyperemesis gravidarum over a 5-year period.
      Women were classified as having severe hyperemesis gravidarum if abnormalities of
      serum electrolytes and liver function tests results were present and as less
      severe if these abnormalities were absent. Almost all women had ketonuria. Mantel
      Haenszel odds ratios, chi 2 analysis and Fisher's 2-tailed exact test were used
      for statistical analysis. RESULTS: The proportion of hyperemesis gravidarum
      patients who were Pacific Islanders was significantly increased when compared to
      their proportion in a control group (p < 0.01). The difference remained
      significant when the hyperemesis patients were divided into less and more severe.
      Abnormal thyroid function test results were more common among Pacific Island
      patients than among nonPacific Island patients. This difference was significant
      (p < 0.01) only in the less severe group. CONCLUSION: The incidence of
      hyperemesis gravidarum is significantly increased among Pacific Island women
      (especially Samoans) living in Wellington and is often associated with
      abnormalities of thyroid function test results.

PMID- 7566764
TI  - Public education and depth of primary malignant melanoma, Hutt Hospital, 1985-92.
AB  - AIMS: To document the depth of primary malignant melanoma treated at the
      Wellington regional plastic and maxillo-facial surgical unit, Hutt Hospital, from
      1985-92. To determine the effects of public education campaigns commenced in
      1987, on the presentation of melanoma at Hutt Hospital, and to ascertain whether
      the Department of Health, Health Goals for 1995 were attained in relation to Hutt
      Hospital. METHODS: A surgical audit was established in 1985 to record all cases
      of melanoma treated at the plastic surgical unit, Hutt Hospital. Data relating to
      the depth (Breslow index) of each primary melanoma was extracted from this audit,
      and reviewed. Metastatic or recurrent disease was excluded. RESULTS: The number
      of cases of primary melanoma treated at this unit increased greatly following the
      Cancer Society initiated Spotcheck programme in 1987. There was a significant
      increase (p < 0.001) in the number and proportion of thin (less than 0.76mm)
      invasive melanomas treated, from 30% of the total in 1985, through to 70% in
      1992. There was no increase in the actual number of thick (> 0.75mm) invasive
      melanoma, with the total number of cases being treated remaining relatively
      constant from 1989 onwards. CONCLUSIONS: Significantly more patients are
      presenting with thin melanoma. This may be due to the nature of the disease
      itself, alterations in referral patterns, or due to earlier identification of
      malignant lesions due to greater public education. The education campaigns appear
      to be responsible for the observed increase in cases of melanoma presenting to
      our unit. The Department of Health goals for 1995 have already been achieved with
      > 60% of primary malignant melanoma being < 0.76 mm in depth at time of
      presentation.

PMID- 7566765
TI  - A survey of allopurinol dosage prescribing.
AB  - AIM: To evaluate the appropriateness of allopurinol dosage according to renal
      function in patients at Dunedin and Wakari hospitals. METHOD: A prospective
      survey of all patients receiving allopurinol therapy at Dunedin and Wakari
      hospitals during a four week period in January/February 1994 was performed. Data
      were collected from medication charts, patient notes and laboratory records.
      Dosage prescribed was compared with established guidelines. RESULTS: Of 46
      patients on allopurinol treatment 18 were prescribed at least 100 mg more than
      the recommended daily dose. Twenty-nine out of the 46 surveyed patients (median
      age 77 years) had mild to moderate renal impairment. CONCLUSIONS: A significant
      proportion of patients were receiving excessive doses. Although information
      regarding the allopurinol hypersensitivity syndrome and individualised
      allopurinol dosage is available, it is evident that many practitioners remain
      unaware of the recommendations.

PMID- 7566766
TI  - The Long case: a case for change.

PMID- 7566767
TI  - Guidelines for the use of granulocyte colony stimulating factor (G-CSF)

PMID- 7566768
TI  - Guidelines for the use of granulocyte colony stimulating factor (G-CSF)

PMID- 7566769
TI  - Breast cancer screening.

PMID- 7566770
TI  - Guidelines for the use of granulocyte colony stimulating factor (G-CSF)

PMID- 7566771
TI  - Stroke units.

PMID- 7566772
TI  - Breastfeeding rates in New Zealand in the first 6 months and the reasons for
      stopping.
AB  - AIM: To assess the prevalence of breastfeeding in the first 6 months post partum,
      and to elicit the reasons for stopping breastfeeding. METHODS: A longitudinal
      cohort study of 4286 New Zealand infants born between 2 July 1990 and 30 June
      1991. Mothers were asked at 6 weeks, 3 months and 6 months whether they were
      breastfeeding or had ever breastfed their babies. If they had breastfed their
      babies but had now stopped breastfeeding, they were asked how old the baby was
      when they stopped and the reasons for stopping. RESULTS: Feeding data was
      available on 3929 of the 4286 infants enrolled in the study. At birth 93.8% (n =
      3685) infants were exclusively breastfed. No infants were partially breastfed. At
      6 weeks, 3 months and 6 months post partum, the breastfeeding rates were 79.5%
      (68.4% exclusive), 71.3% (47.6% exclusive), and 56% (2.5% exclusive),
      respectively. The most common reason for stopping breastfeeding was perceived
      inadequate supply of breast milk (29%, 29% and 33% of mothers who stopped between
      birth to 6 weeks, 6 weeks to 3 months and 3 months to 6 months, respectively),
      apart from Pacific Island mothers, whose main reason for stopping breastfeeding
      between six weeks and three months post partum was returning to work or study
      (38% of mothers who stopped). CONCLUSIONS: The decline in breastfeeding rates
      with length of time post partum could be reduced with education of breastfeeding
      mothers and health professionals about the management of breastfeeding problems
      and early infant behaviour and growth. Support by employers or education
      facilities for breastfeeding mothers who are working or studying may help to
      maintain breastfeeding rates.

PMID- 7566773
TI  - Respiratory symptoms and environmental factors in schoolchildren in the Bay of
      Plenty.
AB  - AIMS: To determine the prevalence of respiratory symptoms in children and to
      examine associations with environmental factors in the Bay of Plenty. METHODS:
      International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires
      were distributed to 13-14 year old children and to care-givers of 6-7 year old
      children as part of the ISAAC study. RESULTS: Completed questionnaires were
      received for 2614 primary and 2752 secondary students. Analysis by district
      showed no consistent association with exposure to industrial emissions from paper
      mills, natural sulphur fumes, or climatic variation. All districts are subject to
      high levels of pollen. Symptom prevalence was close to the mean for New Zealand
      centres participating in the ISAAC survey. Night cough and nasal symptoms were
      more common in secondary pupils exposed to smoking in the home, but there was no
      consistent association between passive smoking and wheeze or diagnosed asthma.
      Children from larger households reported less wheezy symptoms and less diagnosed
      asthma. CONCLUSIONS: There was no consistent evidence of an effect on respiratory
      morbidity from natural fumes, industrial air pollution, or climate. The indoor
      environment is probably of greater importance in this population.

PMID- 7566774
TI  - Geographical variations in the organisation of general practice.
AB  - AIMS: To describe organisational characteristics of New Zealand general practice
      and to investigate inter-regional variations in these characteristics. METHODS:
      Data were collected by standardised questionnaires from general practitioners in
      Auckland, Waikato and Taranaki. The Waikato data were collected in July-August
      1991 by postal survey, the Taranaki data were collected May-June 1992 by postal
      survey and the Auckland data were collected December 1990 to January 1991 by face
      to-face interview. RESULTS: The response rates were Auckland 98% (167/171),
      Waikato 84% (185/220) and Taranaki 79% (79/100). There were significantly more
      overseas trained graduates in rural areas than in urban areas. Average practice
      size was 2.3 full time equivalent doctors, with each 100 doctors employing 71
      nurses and 77 receptionists. The number of patients seen per week ranged from 109
      141. Almost all (95%) general practitioners operated appointment systems. One in
      five general practitioners had patients in private hospitals, and more than half
      (58%) had patients in rest homes. At the time of interview, 29% of Auckland
      general practitioners used computers in their practices compared with over 50% in
      Waikato and Taranaki (p < 0.05). A smaller proportion of Auckland general
      practitioners had access to age/sex registers and fewer Auckland general
      practitioners had a recall system. Of Auckland general practitioners with recall
      systems, a greater proportion used them for mammograms, blood pressure and lipid
      measurements compared with elsewhere. CONCLUSIONS: There are some significant
      regional variations in the functional characteristics of general practice in New
      Zealand which should be taken into account when planning primary care services in
      different regions. Should budget holding and managed care be introduced,
      computerised practices will be required. This will have significant resource
      implications.

PMID- 7566775
TI  - Hepatitis C seroprevalence amongst injecting drug users attending a methadone
      programme.
AB  - AIM: To study the seroprevalence of the hepatitis C virus (HCV) amongst a
      population of injecting drug users and to examine the relationship between
      potential risk factors and HCV infection. METHODS: A sample of 116 clients
      attending a methadone treatment clinic in Christchurch took part in this study.
      Blood samples were analysed to detect antibodies to HCV and to test for HCV RNA:
      Serum transaminases were also measured. In addition a short questionnaire about
      sexual behaviour and drug use practices was self completed by all participants in
      strictest confidence. RESULTS: Slightly more than half the sample were female
      (54.3%) and most were of European origin (90.6%). The average age was 31.56 years
      and the average length of time they had been injecting drugs was 9.54 years. HCV
      antibodies were detected in 84.2% of the sample and HCV RNA in 66.1% of the
      sample including 75.9% amongst those who were anti-HCV positive and 16.6% amongst
      those who were anti-HCV negative. AST and ALT levels were elevated amongst 16.8%
      and 46.2% of the sample respectively. The likelihood of being anti-HCV positive
      increased with years of drug use and with increased sharing of injecting
      equipment. No significant relationship between HCV status and sexual practices
      was evident. Data on the history of drug using practices indicated that sharing
      of injecting equipment had become less common over time and access to new
      equipment through reliable sources had become more common with time. CONCLUSIONS:
      HCV is widespread amongst this population of injecting drug users suggesting the
      possibility of a major clinical and social problem. Despite evidence of a
      reduction in the sharing of injecting equipment, HCV transmission is still
      occurring indicating the potential for other parenterally transmitted diseases,
      such as HIV, to become established amongst injecting drug users. Those at high
      risk of HCV should be discouraged from donating blood because of the possibility
      of HCV seronegative infectivity.

PMID- 7566776
TI  - The incidence of hip fractures in Maori and non-Maori in New Zealand.
AB  - AIMS: To investigate the incidence of hip fractures in Maori and nonMaori in New
      Zealand. METHODS: The number of femoral neck fractures in patients over 60 in New
      Zealand for the years 1989-91 were obtained. The population data for 1991 was
      obtained from the 1990 census. The number of fractures was standardised for age,
      and the rate of fractures per 100,000 of population calculated. RESULTS: The age
      standardised rates of hip fracture per 100,000 of population 1989-91 for Maori
      males was 197, Maori females 516, nonMaori males 288 and nonMaori females 827.
      These rates were higher than the rates recorded between 1973 and 1975.
      CONCLUSIONS: The age-specific hip fracture rate is rising in New Zealand. However
      in Maori males the rate is not rising.

PMID- 7566777
TI  - Unrecognised arterial injury of the forearm: presenting as acute compartment
      syndrome.

PMID- 7566778
TI  - Immunisation rates of infants.

PMID- 7566779
TI  - Breast cancer screening.

PMID- 7566780
TI  - A lost pathological specimen.

PMID- 7566782
TI  - Cot death and cot mattresses.

PMID- 7566781
TI  - Bed sharing and cot death.

PMID- 7566783
TI  - Neonatal BCG vaccine.

PMID- 7566784
TI  - Transoesophageal echocardiography in patients with prosthetic heart valves and
      systemic emboli: is it a useful investigation?
AB  - AIM: We aimed to assess the impact of transoesophageal echocardiography (TOE) on
      the clinical management of patients with prosthetic heart valves who had suffered
      from a systemic embolus. We wanted to know whether the TOE examination actually
      changed the management of these patients. METHODS: Prospective assessment of 38
      TOE studies, with retrospective chart review of the hospital treatment. RESULTS:
      In 16 TOE studies, no potential cardiac source of emboli was found, however in 22
      studies a cardiac abnormality was detected. As a result of the TOE, in 13 cases
      there was a definite change in clinical management for the patient. CONCLUSION: A
      TOE is an important examination for patients with a prosthetic valve who present
      with a systemic embolus.

PMID- 7566785
TI  - Transport of the critically ill patient: an example of an integrated model.
AB  - AIMS: To demonstrate a model for the transport of critically ill patients between
      hospitals, and the aiding of primary emergency responses (A-Zeros). METHOD: A
      review of a model based on Waikato Hospital is carried out. RESULTS: Categories
      of transport, modes of transport, standards, and the funding model are described.
      The total Waikato experience includes over 2500 patients transported between
      hospitals and 325 A-Zeros. A detailed analysis of cases between 1988-94 is
      presented. CONCLUSIONS: The Waikato model has worked well. A formal system needs
      to be instituted in New Zealand to handle interhospital transport of the
      critically ill and also to provide medical help at the scene of emergencies based
      on advanced trauma and intensive care centres.

PMID- 7566786
TI  - Imported malaria in Auckland in 1993.
AB  - AIM: To determine the number of people with malaria in Auckland in 1993 and
      determine species, sources, exposure history, use of chemoprophylaxis, outcome
      and geographic attack rates. METHODS: We prospectively obtained the numbers of
      people with laboratory diagnosed malaria from all haematology departments in
      Auckland and then contacted the patients and their doctors to elicit further
      details. RESULTS: Forty three people, 30 men and 13 women, had malaria. Twenty
      eight were New Zealanders, 10 migrants, three temporary visitors and two not
      determined. Thirty two had P vivax infection, 11 P falciparum: none had
      complications. The highest attack rate was in travellers to the Solomon Islands.
      Eighty two per cent took prophylaxis. CONCLUSIONS: Malaria is an uncommon
      diagnosis in Auckland. Most patients took prophylaxis. The disease is
      undernotified. No one died of malaria in 1993 in Auckland.

PMID- 7566787
TI  - Adverse reactions associated with nefopam.
AB  - AIM: To review postmarketing experience of adverse reactions associated with
      nefopam. METHODS: Spontaneous reports of adverse reactions associated with
      nefopam over a 12 year period received by the New Zealand Centre for Adverse
      Reactions Monitoring were reviewed. RESULTS: There were 70 reports of adverse
      reactions thought to be causally related to nefopam, most of which appear to be
      predictable extensions of the pharmacological effect of nefopam, and included
      confusion, hallucinations, convulsions, dizziness, headache, sweating, urinary
      retention, nausea, vomiting, tachycardia and palpitations. The first report of
      angina is described. Convulsions occurred in a stable epileptic in whom nefopam
      was contraindicated, and in another where the seizure threshold may have been
      lowered by a concomitant tricyclic antidepressant. CONCLUSIONS: Nefopam can cause
      unpleasant adverse effects and there are important cautions and contraindications
      with this analgesic. A clearer presentation of its basic pharmacology in the
      datasheet should help to ensure appropriate use.

PMID- 7566788
TI  - Assessment of rubella immunity in women born in 1959-74 in a solo rural general
      practice.
AB  - AIM: To evaluate the rubella immunity of all women in the practice born 1959-74.
      METHOD: A chart audit followed by offering testing to all women whose rubella
      status was unknown. RESULTS: According to their records, of 203 female patients
      born 1959-74, 149 (73%) were immune to rubella and 54 were not. All of the 54
      nonimmune women agreed to rubella testing and only three were found to be
      susceptible. These three women had never been pregnant before, none were from the
      higher risk cohort born 1965-7 and all accepted vaccination. CONCLUSION: For
      general practitioners it is important to assess the rubella immunity of all women
      of childbearing age in their practice, especially those who have never been
      pregnant and not just the high risk cohort born 1965-7.

PMID- 7566789
TI  - Lymphocutaneous Nocardia brasiliensis infection: a case report and review.

PMID- 7566790
TI  - The challenge of the continuing effects of poliomyelitis in New Zealand.

PMID- 7566791
TI  - Physiological wheezing.

PMID- 7566793
TI  - Tuberculosis revisited.

PMID- 7566792
TI  - Utstein style format for cardiac arrest analysis.

PMID- 7566794
TI  - Brucellosis eradication scheme successfully completed.

PMID- 7566795
TI  - Chronic fatigue syndrome.

PMID- 7566796
TI  - Occupational overuse syndrome.

PMID- 7566797
TI  - Adverse drug reaction to oxethazine: a case report.

PMID- 7566798
TI  - Screening for hepatocellular carcinoma in hepatitis B carriers.

PMID- 7566799
TI  - Go to someone, ask for help...

PMID- 7566800
TI  - Searching for managed care savings.

PMID- 7566802
TI  - Liability in managed care for the health care provider.

PMID- 7566801
TI  - Capitation: implications for subacute care.

PMID- 7566803
TI  - Mobile access: opening health care doors.
AB  - By combining traditional services and resources, the HealthQuest mobile van
      travels through six counties in northeast Indiana to reach those who have no easy
      access to health care. Existing programs that focus on meeting the needs of
      infants, children and adults living in rural communities via the use of mobile
      primary care vans are reviewed as well as this recently developed program.

PMID- 7566804
TI  - Emergency department patient classification system.
AB  - Very little has been reported about costing out nursing services in emergency
      departments. In this study, an emergency care unit (ECU) worked with consultants
      to adapt the hospital patient classification system to provide more accurate ECU
      service charges for nursing care.

PMID- 7566805
TI  - Express admission: an experiment in front-end redesign.
AB  - A redesigned admitting procedure includes simplifying and compressing all
      processes that occur during the first 24 hours after admission. Centralizing
      admissions procedures resulted in reducing actual admitting time to 80 minutes.
      Decreased length of stay is indicated as a probable result of the redesign.

PMID- 7566807
TI  - Surviving a client/server migration.

PMID- 7566806
TI  - Increasing the validity of a quality monitoring methodology.
AB  - A practice model for assessing and increasing the validity of a quality
      monitoring instrument is identified. The philosophical and economic factors,
      assessment and the project's steps and strategies for maintaining the tool's
      validity are discussed.

PMID- 7566808
TI  - Disclosure of health care workers with HIV or AIDS.
AB  - Every health care organization should have clear policies about how employees
      with HIV/AIDS are to be accommodated under employment laws. Managers should be
      knowledgeable about discrimination laws in order to handle reactions of co
      workers. Administrators must ensure that educational sessions are provided for
      all levels of staff. Informational brochures on HIV/AIDS should be available to
      families and to businesses and other community organizations.

PMID- 7566809
TI  - Accuracy of interpreting human responses.
AB  - Nurse managers who advocate continuous quality improvement should be examining
      system-level policies, procedures and attitudes to determine whether they support
      or detract from accuracy of nurses' interpretations of human responses. A study
      discusses the relationship of accuracy of nurses' diagnoses to continuous quality
      improvement and demonstrates why nurse managers should focus on accuracy in
      system-level decisions. Four guidelines, which emphasize quality of interventions
      and outcomes, are given.

PMID- 7566811
TI  - Interdisciplinary collaboration: strengthening documentation.
AB  - The JCAHO's "Agenda for Change" initiative contains new and revised standards for
      acute care facilities. To meet these, nursing departments will have to reevaluate
      current forms and documentation to ensure that collaborative interdisciplinary
      practice is demonstrated. Development and use of one such form is described.

PMID- 7566812
TI  - Nursing home staff--nursing student partnership.
AB  - A partnership between a nursing home and a school of nursing provides both staff
      and students with creative opportunities for solving clinical problems. Through
      collaborative efforts of senior baccalaureate students and the staff
      administration of a long-term care facility in eastern Virginia, a successful
      bowel management program was developed and implemented.

PMID- 7566810
TI  - A leadership development series.
AB  - A detailed step-by-step series--assessment, development, implementation and
      evaluation--forms a leadership program's structure. Main topics are identified;
      subtopics, chosen to meet the participants' specific needs, are developed from
      modules. Participants make the transition from each leadership unit: self-esteem
      and professional image; assertive communication; collaboration; problem-solving;
      coaching/mentoring; and time management/resource utilization.

PMID- 7566814
TI  - Ethics in management. Good intentions aside.

PMID- 7566815
TI  - The politics of welfare reform.

PMID- 7566813
TI  - Peer-to-peer accountability.
AB  - Peer-to-peer accountability is an essential component of empowerment-based
      management models. To foster this environment, skills such as conflict
      resolution, team building, communication and group dynamics need to be identified
      and supported. The lack of peer-to-peer accountability can seriously hinder the
      development of management models.

PMID- 7566817
TI  - Geriatric assessment + nursing diagnosis = care plan.

PMID- 7566816
TI  - An organizational plan for patient assessment/reassessment.

PMID- 7566818
TI  - Ventilator-dependent patients on a medical unit.

PMID- 7566819
TI  - Productivity and peerage.

PMID- 7566820
TI  - The "gold collar" leader...?

PMID- 7566821
TI  - The illegal practice of dentistry.

PMID- 7566822
TI  - Experience counts.

PMID- 7566823
TI  - Read it again.

PMID- 7566824
TI  - Quacks among us.

PMID- 7566825
TI  - Lip service.
AB  - Questionnaires addressing the attitudes of football officials toward National
      Collegiate Athletic Association (NCAA) mouthguard rules were developed and
      distributed to officials in the Big East Football Conference, the Southeastern
      Conference, and to head football coaches at Division 1-A colleges. Response
      rates, which ranged from 92.45% to 100%, showed that all groups agreed that
      football officials are less accountable for player compliance than are coaches,
      trainers and players. However, officials not only observed a lower rate of
      compliance with NCAA mouthguard regulations than coaches, they also expressed
      reluctance to enforce NCAA-sanctioned penalties for failure to comply with
      mouthguard regulations.

PMID- 7566826
TI  - Treatment of a traumatic tooth avulsion.
AB  - The traumatic avulsion of a tooth presents unique and challenging difficulties in
      patient management. The successful replantation of the avulsed tooth is
      influenced by many factors occurring from the moment of injury to the moment of
      replantation. Immediate and decisive treatment is essential in this time period
      to avoid subsequent inflammatory root resorption and ankylosis.

PMID- 7566827
TI  - Orofacial trauma management. Patient assessment and documentation.
AB  - New technologies and treatments for managing children with orofacial trauma are
      constantly updated and available to the practitioner through current literature.
      What often fails to be appreciated, however, is that orofacial injury is a subset
      of head trauma and may have systemic emergent considerations that supersede the
      oral conditions being addressed. The complexity of a thorough assessment of the
      child from both medical and dental standpoints requires a systematic approach,
      which in turn can be guided by an appropriate document for inclusion in the
      chart. Further, such a document will serve as an important record should future
      civil litigation ensure from the traumatic incident.

PMID- 7566830
TI  - Support groups: a neglected resource in obstetrics and gynecology.

PMID- 7566828
TI  - The first line of defense.
AB  - With children in this country becoming involved in organized sports at younger
      and younger ages, the incidence of dental and orofacial injuries is on the rise,
      and the practice of sports dentistry is needed more than ever. This article
      focuses on the costs of dental injuries and measures that can be taken to
      significantly reduce the risk of injury.

PMID- 7566829
TI  - Selling/buying a dental practice.
AB  - The times they are a'changing, along with the way dental practices are acquired
      and offered for sale. It behooves both the dentist who is looking to buy a
      practice and the dentist who is thinking about disposing of a practice to
      thoroughly understand the rules of the game.

PMID- 7566831
TI  - Use of thrombolytics for the treatment of thromboembolic disease during
      pregnancy.
AB  - The incidence of thromboembolic disease is increased during pregnancy. Prevention
      and treatment of thromboembolic disease can have a significant impact on the
      morbidity and mortality of pregnant women. Anticoagulation with heparin is the
      treatment of choice; however, in some instances this is inadequate or
      contraindicated. In the nonpregnant patient, alternative therapies have included
      surgical intervention or fibrinolytic agents. Traditionally, thrombolytic therapy
      has been considered a relative contraindication during pregnancy due to the
      maternal and fetal risk of hemorrhagic complications. Hence, no controlled trials
      of agents such as streptokinase, urokinase, or tissue plasminogen activator for
      the treatment of thromboembolic events during pregnancy, have been performed, or
      are currently feasible. Since 1961, 36 reports have been published describing the
      use of thrombolytic agents during pregnancy. In a review of the world's
      literature, 172 pregnant women affected with thromboembolic conditions were
      treated with thrombolytic medications. A maternal mortality rate of 1.2 percent
      was observed. Approximately 10 pregnancy losses were noted (5.8 percent).
      Hemorrhagic complications were reported in 8.1 percent of patients. We summarize
      the published literature on the use of thrombolytic agents during pregnancy and
      discuss the treatment success and reported complications.

PMID- 7566832
TI  - Respiratory distress syndrome of the newborn infant.
AB  - Pulmonary immaturity, including deficiency in the surfactant system, incomplete
      structural/functional development of lungs and high chest wall compliance
      contribute to the pathogenesis of respiratory distress syndrome (RDS). Pulmonary
      edema and overperfusion, resulting from a patent ductus arteriosus, may further
      worsen the respiratory failure, and aggravate the surfactant deficiency. Infants
      born prematurely present with respiratory distress within the first few minutes
      of life. This quickly becomes life-threatening, and may result in death from
      severe respiratory failure if appropriate respiratory and general supportive
      therapy are not immediately instituted. The oxygenation deficit in RDS is
      secondary to V/Q mismatch and right-left shunting of blood via pulmonary and
      extrapulmonary routes. Hypoxemia induced pulmonary vasoconstriction further
      contributes to V/Q mismatch and R-L shunting. Hypoventilation in RDS is due to
      decreased tidal volume, increased dead space ventilation, and finally, decreased
      minute ventilation. Characteristically, pulmonary compliance, both static and
      dynamic, are greatly reduced resulting in a high work of breathing, whereas
      airway resistance is normal or only slightly increased. This combination of
      abnormal pulmonary mechanics results in lower respiratory time constant in
      respiratory units, and helps in achieving ventilation and oxygenation by using
      low inspiratory time in the ventilator. Management of RDS starts with prenatal
      identification of the risk, prolongation of pregnancy by tocolysis and prenatal
      administration of pharmacological agents, like betamethasone. These agents
      increase the pulmonary gas exchange surface area and induce endogenous pulmonary
      surfactant in the fetus. Advances in ventilatory and general management
      techniques have strikingly improved the outcome and prognosis of children
      suffering from RDS since the 1960s. Recent advancements in the prevention and
      treatment of RDS, e.g., acceleration of lung development by prenatal
      pharmacological manipulations and postnatal provision of exogenous surfactant,
      have significantly contributed to the decrease in mortality from RDS.
      Pharmacological induction of lung maturation by drugs in combination, and
      improved technology in lung ventilation are expected to further improve the
      course and outcome of the disease in future.

PMID- 7566833
TI  - Acute spinal cord injury and neurogenic shock in pregnancy.
AB  - A case of a pregnant woman with a subluxation of C-6 on C-7 with acute
      quadriplegia and sensory loss to the T-10 dermatome is described. Hemodynamic and
      fetal monitoring during the 3-week period of neurogenic shock resulted in good
      maternal and fetal outcomes. Pulmonary complications and anesthetic issues are
      important aspects of the care of these critically ill patients. Major trauma is a
      common cause of death and disability in young adults and may contribute to as
      much as 15 percent of nonobstetric maternal deaths. Spinal cord injuries involve
      young women in 15 percent of cases. The literature is replete with information on
      the obstetric management of patients with preexisting spinal cord injury (1-4)
      but there is little on the management and special problems of the pregnant
      patient with acute spinal cord trauma. We report here the management of a case of
      acute cord transection accompanied by spinal shock and discuss the specific
      maternal as well as fetal considerations in this syndrome.

PMID- 7566834
TI  - Determining the time before birth when ischemia and hypoxemia initiated cerebral
      palsy.
AB  - OBJECTIVE: To test the hypothesis that lymphocyte and normoblast counts in
      neonatal blood can be used to identify the time that ischemia and hypoxemia
      produced cerebral palsy. METHODS: Blood lymphocyte and normoblast counts were
      analyzed at intervals after birth in 16 neonates for whom we knew the time when
      antenatal ischemic and hypoxemic brain damage began. These counts were compared
      with counts from normal newborns, infants with low Apgar scores and no cerebral
      palsy, and infants with cerebral palsy caused by developmental and other early
      gestational disorders. RESULTS: Lymphocyte counts increased to more than
      10,000/mm3 and normoblast counts to 2000/mm3 or more within 2 hours after the
      brain-damaging ischemia and hypoxemia began. Lymphocyte counts returned to normal
      levels 24 hours after the damaging event took place, and normoblast counts in 24
      36 hours. Normal neonates had a mean +/- one standard deviation lymphocyte count
      of 4430 +/- 1418/mm3 and a normoblast count of 560 +/- 771/mm3. CONCLUSION:
      Following the changing counts of lymphocytes and normoblasts in neonates' blood
      may accurately identify the time before birth when brain-damaging ischemia and
      hypoxemia began.

PMID- 7566836
TI  - Umbilical cord encirclements and fetal growth restriction.
AB  - OBJECTIVE: To establish whether the presence of umbilical cord encirclements
      around the fetal body influence fetal growth. METHODS: The encirclements, cord
      length, gestational age, and fetal weight at birth were recorded for 11,201
      births occurring at our hospital during 1991-1994. RESULTS: The presence of
      umbilical cord encirclements is associated with fetal growth restriction (FGR),
      the severity of the restriction being positively related to the number of
      encirclements. Umbilical cord encirclements are also associated with a relative
      lengthening of the umbilical cord. Because there is a positive correlation
      between cord length and fetal weight, this association tends to offset the
      effects of the encirclements, giving the newborns a more normal birth weight than
      they would have had otherwise. The net result, however, is negative. CONCLUSION:
      Umbilical cord encirclements are associated with FGR.

PMID- 7566835
TI  - Can meconium in the amniotic fluid injure the fetal brain?
AB  - OBJECTIVE: To determine if meconium in the amniotic fluid (AF) can cause cerebral
      palsy by stimulating umbilical and placental blood vessels to constrict. METHODS:
      Brain injury patterns were analyzed in 43 children whose exposure to meconium in
      the AF was their only identified risk for quadriplegic cerebral palsy. The times
      their injuries occurred were established by following lymphocyte counts in their
      blood after birth. RESULTS: All 43 had cerebral cortical and subcortical brain
      damage of the type produced by late gestational ischemia and hypoxemia. The time
      between the onset of injury and birth ranged from 2-38 hours. The neonates were
      severely acidotic at birth when birth occurred within 12-14 hours after ischemia
      and hypoxemia began. Thereafter, the acidosis receded as the time between its
      start and birth increased, presumably because vasoconstriction had ended. Severe
      acidosis did not recede in nine children whose cerebral palsy was due to
      disorders that kept them hypoxemic until birth. CONCLUSION: Meconium in the AF
      may sometimes initiate vasoconstriction that leads to ischemic, hypoxemic
      cerebral palsy.

PMID- 7566837
TI  - Does low-dose combination oral contraceptive use affect uterine size or menstrual
      flow in premenopausal women with leiomyomas?

PMID- 7566838
TI  - Abdominal venous system in the normal fetus.
AB  - OBJECTIVE: To assess flow velocity waveforms of the abdominal venous system in
      the normal fetus. METHODS: Sixty-seven normal fetuses between 17-42 weeks'
      gestation were each studied once. Flow velocity waveforms were obtained from the
      following: 1) umbilical vein at the entrance into the abdomen, 2) umbilical
      sinus, 3) portal vein before its division, 4) anterior division of the portal
      vein, 5) posterior division of the portal vein, 6) ductus venosus at its origin
      from the umbilical vein, 7) splenic vein at its origin, 8) splenic vein close to
      the umbilical sinus, 9) renal vein, 10) adrenal vein, 11) common iliac vein
      before the origin of the inferior vena cava, 12) inferior vena cava, and 13) left
      hepatic vein. RESULTS: Five different patterns were noted on the velocity
      waveforms of the abdominal venous system: continuous, monophasic, biphasic,
      triphasic, and tetraphasic. CONCLUSION: In the normal fetus, all veins leading to
      the liver have continuous flow, except the umbilical sinus, which has a
      monophasic pattern. The ductus venosus has a biphasic pattern. The veins that
      open into the inferior vena cava have triphasic flow velocity waveforms. The left
      hepatic vein occasionally has a tetraphasic pattern.

PMID- 7566839
TI  - Discordant blood flow velocity waveforms in left and right brachial arteries in
      growth-retarded fetuses.
AB  - OBJECTIVE: To determine if the increase in cerebral blood flow ("brain-sparing"
      effect) with fetal hypoxemia is associated with discordant hemodynamics in the
      upper extremities. METHODS: We studied 12 fetuses with severe growth retardation,
      absent or reverse end-diastolic blood flow in the umbilical artery, and low
      pulsatility index (PI) in the middle cerebral artery, and 12 appropriately grown
      control fetuses with normal fetoplacental Doppler studies. The right and left
      brachial arteries were identified by high-resolution color Doppler
      ultrasonography, and the PI was measured in each brachial artery. RESULTS: All
      growth-retarded fetuses had lower impedance indices in the right than in the left
      brachial artery (mean delta PI 1.0, 95% confidence interval [CI] 0.7-1.3, P <
      .001). No differences in the brachial artery impedance indices were found in
      control fetuses matched for gestational age (mean delta PI 0.0, 95% CI -0.2 to
      0.2). CONCLUSIONS: Left and right brachial artery blood flow velocity waveforms
      are discordant in fetuses with growth retardation and cerebral vasodilation.
      Because the right arm receives its blood supply from the same source as the brain
      (brachiocephalic artery) and given the proximity of the left subclavian artery to
      the ductus arteriosus, we speculate that this might be the result of increased
      blood flow into the brachiocephalic circulation and/or functional differences in
      the distribution of left and right ventricular output within the aortic arch in
      response to fetal hypoxemia.

PMID- 7566840
TI  - Prenatal diagnosis of liver calcifications.
AB  - OBJECTIVE: To report our experience with the prenatal diagnosis of hepatic
      calcification. METHODS: Routine ultrasonography was done in 24,600 consecutive
      pregnancies of 14-26 weeks' gestation. Detailed sonographic studies,
      amniocenteses, and chromosomal, bacteriologic, virologic, and serologic
      investigations were performed in each case with calcifications. RESULTS: Hepatic
      calcifications were diagnosed in 14 fetuses--an incidence of one in 1750--at
      gestational ages of 15-26 weeks. Twelve fetuses had one or two calcified foci,
      one fetus had four scattered foci, and one had diffuse calcification of the liver
      as well as peritoneal and intestinal calcifications. Three fetuses (21%) had
      associated severe malformations: two with trisomy 18 and one with dwarfism and
      hydronephrosis; these fetuses were aborted. One fetus with polyhydramnios and
      calcifications within the bowel died in utero; an autopsy was not allowed, but
      the external examination was normal. No case had serologic evidence of recent
      infection with Toxoplasma, rubella virus, cytomegalovirus, herpes simplex virus,
      or syphilis. Amniotic fluid (and neonatal urine where applicable) cultures for
      cytomegalovirus were negative. Ten fetuses were normal at birth, and nine of them
      were followed-up for a period of 4 months to 4.5 years. All were found to be
      healthy and thriving children. CONCLUSION: Our experience indicates that fetal
      hepatic calcification is not a rare ultrasonographic finding, and each fetus with
      such calcifications should be thoroughly evaluated for malformations, chromosomal
      anomalies, and viral infection. If the work-up is negative, subsequent neonatal
      outcome carries a good prognosis.

PMID- 7566841
TI  - Maternal anthropometry and idiopathic preterm labor.
AB  - OBJECTIVE: To assess the etiologic role of maternal short stature, low pre
      pregnancy body mass index (BMI), and low rate of gestational weight gain in
      idiopathic preterm labor. METHODS: We carried out a three-center case-control
      study of 555 women with idiopathic onset of preterm labor (before 37 completed
      weeks), including two overlapping (ie, nonmutually exclusive) subsamples: cases
      with early preterm labor (before 34 completed weeks) and cases with recurrent
      preterm labor (before 37 completed weeks plus a history of prior preterm delivery
      or second-trimester miscarriage). Controls were matched to cases by race and
      smoking history. All subjects responded in person to questions about height, pre
      pregnancy weight, gestational weight gain, and obstetric and sociodemographic
      histories. RESULTS: Maternal height, pre-pregnancy weight, and gestational weight
      gain demonstrated excellent test-retest reliability, with intra-class correlation
      coefficients of 0.97, 0.99, and 0.91, respectively. Based on matched analyses,
      women with a height of 157.5 cm or less had an increased risk of idiopathic
      preterm labor (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.25-2.74), as
      did those with a pre-pregnancy BMI less than 19.8 kg/m2 (OR 1.63, 95% CI 1.09
      2.44) or a gestational weight gain rate less than 0.27 kg/week (OR 1.74, 95% CI
      1.16-2.62). Conditional logistic regression models containing all three
      anthropometric variables and controlling for parity, marital status, language,
      age, and education yielded virtually identical point estimates and CIs.
      CONCLUSION: Maternal short stature, low pre-pregnancy BMI, and low rate of
      gestational weight gain may lead to shortened gestation by increasing the risk of
      idiopathic preterm labor.

PMID- 7566842
TI  - Papanicolaou smears in human immunodeficiency virus-seropositive women during
      follow-up.
AB  - OBJECTIVE: To assess the outcome of cervical squamous intraepithelial lesions
      (SIL) in human immunodeficiency virus (HIV)-seropositive women. METHODS:
      Papanicolaou smears were followed-up prospectively in a group of 60 HIV-positive
      women every 6 months for 18 months. RESULTS: The cumulative incidence of SIL at
      18 months was 9% in 27 women who presented with normal Papanicolaou smears at
      entry. In 33 women who initially presented with SIL, the rate of persistence of
      cervical lesions was 95% (18 of 19) in untreated patients and 61% (eight of 13)
      in women who underwent surgery. In women with low-grade SIL, the persistence or
      progression of cervical lesions was observed in 92% of the cases (12 of 13). No
      invasive cancer was observed during the 18 months of the study period.
      CONCLUSION: Although the long-term outcome of SIL in this population remains
      unknown, our results emphasize the high rate of persistence of SIL and the
      relative inefficiency of conventional treatment in HIV-infected women. These
      findings contrast with the natural history of SIL in immunocompetent women.

PMID- 7566843
TI  - Determinants of high-grade dysplasia among women with mild dyskaryosis on
      cervical smear.
AB  - OBJECTIVE: To identify the epidemiologic characteristics of women who have mild
      dyskaryosis on cervical smear but cervical intraepithelial neoplasia (CIN) grade
      II or III at biopsy. METHODS: We analyzed information from 291 women (median age
      33 years, range 17-69) observed for the first time with a single smear test
      showing mild dyskaryosis. All subjects underwent colposcopy, and histologic
      confirmation was obtained by biopsy. We compared the characteristics of women who
      had CIN I or no evidence of CIN with those of women with CIN II or III at biopsy.
      RESULTS: Twenty-eight women (10%) had CIN I at biopsy, 46 (15%) CIN II, and 23
      (8%) CIN III. The frequency of CIN II or III tended to decrease with increasing
      education; compared with women reporting 11 or fewer years of education, the
      multivariate odds ratios (OR) of CIN II or III lesions was 0.5 (95% confidence
      interval [CI] 0.3-0.9) in those reporting 11 years of education or more. Compared
      with nulliparas, the OR of CIN II or III was 1.8 (95% CI 1.1-3.5) for parous
      women. Furthermore, compared with never-smokers, the OR of CIN II or III was 2.3
      (95% CI 1.0-5.4) for current smokers. Ex-smokers were at increased risk, too; the
      estimated multivariate OR was 3.8 (95% CI 1.9-7.6). Compared with women reporting
      one sexual partner, the multivariate ORs of CIN II or III were 1.4 and 2.3 for
      women reporting two to three or four or more sexual partners, respectively (chi
      2(1) trend = 6.65, P < .05). CONCLUSION: Our results show that smoking is a risk
      indicator of CIN II or III in women with a single smear showing mild dyskaryosis.
      Parous women, those of low social standing, and those reporting multiple sexual
      partners also are at increased risk of CIN II or III.

PMID- 7566844
TI  - Histologic and biomolecular aspects of papillomatosis of the vulvar vestibule in
      relation to human papillomavirus.
AB  - OBJECTIVE: To determine whether human papillomavirus (HPV) plays a role in the
      genesis of papillomatosis of the vulvar vestibule. METHODS: We conducted a study
      based on molecular hybridization and histology of biopsy material obtained from
      the inner surface of the labia minora of 25 women with papillomatosis of the
      vulvar vestibule who presented no abnormal clinical, cytologic, or colposcopic
      changes in the cervix or vagina. These women were compared with 24 women with
      condyloma acuminatum of the vulvar vestibule and with ten women with normal
      vulvar epithelium and no cervicovaginal changes. All patients included in the
      study were 35 years or younger, and none was pregnant. RESULTS: Papillomatosis of
      the vulvar vestibule was rarely found to be HPV positive by molecular
      hybridization (one of 25, 4%, by dot blot hybridization and one of 15, 6.67%, by
      polymerase chain reaction [PCR]). This result did not differ significantly from
      that obtained for the group with normal vulvar epithelium (none of 10 by dot blot
      and none of six by PCR), but did differ (P = .001) from the result obtained for
      the group with condyloma acuminatum of the vestibule (12 of 24, 50%, by dot blot
      and six of six, 100%, by PCR). The biomolecular study of vestibular
      papillomatosis showed that focal koilocytosis was not correlated with HPV
      infection. CONCLUSION: Papillomatosis of the vulvar vestibule is not associated
      with HPV and should be considered a paraphysiologic formation of the vulvar
      epithelium. The diagnosis of vulvar HPV infection should be avoided in the
      absence of more explicit clinical-histologic evidence, with no need for biopsies
      or unnecessary treatments.

PMID- 7566845
TI  - Rate of hospitalization for gynecologic disorders among reproductive-age women in
      the United States.
AB  - OBJECTIVE: To analyze reproductive-tract disorders that resulted in
      hospitalization of reproductive-age women in the United States. METHODS: Data
      from the National Hospital Discharge Survey for 1988, 1989, and 1990 were used to
      study women 15-44 years old who had any gynecologic diagnoses noted in their
      discharge summaries. RESULTS: Based on average annual discharge rates per 10,000
      women, the five most frequent diagnostic groups were pelvic inflammatory disease
      (PID) (average annual rate 49.3, 95% confidence interval [CI] 43.6-55.0), benign
      cysts of the ovary (average annual rate 32.7, 95% CI 28.8-36.6), endometriosis
      (average annual rate 32.4, 95% CI 28.5-36.3), menstrual disorders (average annual
      rate 31.4, 95% CI 27.6-35.2), and uterine leiomyomas (average annual rate 30.4,
      95% CI 26.7-34.1). The highest rates for PID were among women 25-39 years old and
      for women of races other than white. Highest rates for uterine leiomyomas were
      among women 40-44 years old and for women of races other than white. Highest
      rates for endometriosis were among women 40-44 years old and white women. Racial
      difference existed among all ages in the uterine leiomyoma and endometriosis
      groups. Average annual rates of benign cysts and menstrual disorders increased
      with age, but there were no statistically significant differences according to
      race in these two diagnostic groups. CONCLUSIONS: Our findings confirmed the
      importance of PID as a common cause of hospitalization among reproductive-age
      women and identified additional gynecologic conditions as causes for
      hospitalization as well. We found significant age and racial differences not only
      among women with discharge diagnoses of PID but also among those with discharge
      diagnoses of uterine leiomyomas and endometriosis.

PMID- 7566846
TI  - Treatment of nonendometriotic benign adnexal cysts: a randomized comparison of
      laparoscopy and laparotomy.
AB  - OBJECTIVE: To compare laparoscopy and laparotomy in the management of benign
      adnexal cysts, with particular attention to postoperative convalescence. METHODS:
      Forty premenopausal, nonpregnant women, 18-40 years of age and without acute
      pelvic symptoms, were scheduled to undergo surgical management of anechoic,
      unilateral, unilocular, persistent adnexal cysts from January 1993 through June
      1994 at the Department of Obstetrics and Gynecology of the University of
      Cagliari, Cagliari, Italy. After ultrasonographic examination, followed by the
      completion of 6 months' expectant management with repeat ultrasonographic
      evaluations, subjects were randomized to undergo operative laparoscopy (n = 20)
      or laparotomy (n = 20). The patients were reviewed postoperatively at the out
      patient clinic at 15, 30, 90, and 180 days. The intensity of pain was assessed by
      completion of a visual analogue scale on the results of the two groups were
      compared. We also compared the proportions of patients who were analgesic-free on
      day 2, discharged from hospital within 3 days, and feeling fully recuperated on
      day 15. RESULTS: The intensity of postoperative pain was significantly lower (P <
      .05) in the operative laparoscopy group than in the laparotomy group. A
      significantly higher (P < .05) proportion of the laparoscopy patients was
      analgesic-free on day 2, discharged from the hospital within 3 days, and feeling
      fully recuperated on postoperative day 15. CONCLUSION: After careful patient
      evaluation, management of anechoic, unilocular adnexal cysts by operative
      laparoscopy significantly reduces both the intensity of postoperative pain and
      the length of convalescence compared with laparotomy.

PMID- 7566847
TI  - The changing clinical presentation of complete molar pregnancy.
AB  - OBJECTIVE: To determine if the clinical presentation of complete hydatidiform
      mole has changed in recent years compared with historic controls (1965-1975).
      METHODS: Chart review of all 74 patients referred to the New England
      Trophoblastic Disease Center for the primary management of complete hydatidiform
      mole during 1988-1993 was performed and comparison made to historic controls
      (1965-1975). RESULTS: Vaginal bleeding remained the most common presenting
      symptom, occurring in 62 of 74 (84%) current patients, compared with 297 of 306
      (97%) controls (P = .001). However, anemia was present in only four of 74 (5%)
      current patients, compared with 165 of 306 (54%) controls (P = .001). Excessive
      uterine size, preeclampsia, and hyperemesis occurred in only 21 of 74 (28%), one
      of 74 (1.3%), and six of 74 (8%) current patients, respectively, compared with
      156 of 306 (51%), 83 of 306 (27%), and 80 of 306 (26%), respectively, of historic
      controls (P = .001). No cases of clinical hyperthyroidism or respiratory distress
      were found in recent years. Ultrasound diagnosed complete hydatidiform mole
      before the onset of clinical symptoms in seven of 69 (10%) current patients.
      Among patients not receiving chemoprophylaxis, persistent gestational
      trophoblastic tumor developed in 23% of current patients and 18.6% of historic
      controls. CONCLUSION: Fewer current patients with complete hydatidiform mole
      present with the traditional symptoms of complete hydatidiform mole (excessive
      uterine size, anemia, preeclampsia, hyperthyroidism, or hyperemesis) when
      compared with historic controls. However, there has been no statistically
      significant change in the development of persistent gestational trophoblastic
      tumor in current patients compared with historic controls.

PMID- 7566848
TI  - Malignant mixed mesodermal tumors of the ovary.
AB  - OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford
      Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to
      review the pertinent literature. METHODS: Fourteen cases of malignant mixed
      mesodermal tumors of the ovary at the two hospitals over a 5-year period were
      identified through their tumor registries. Demographic data, pathology,
      treatment, and survival rates were reviewed. RESULTS: The median survival of the
      patients in our series was 7 months, with 64% dead of disease in 1 year. A review
      of the pertinent literature indicated median survivals of 6-12 months, with more
      than 70% of the patients dead of disease at 1 year, despite treatment.
      CONCLUSION: Further investigation is needed to determine the proper management
      for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment
      strategies should recognize the present therapeutic limitations, so as not to
      diminish any further the quality of life for women with this malignancy.

PMID- 7566850
TI  - Risk factors for fever in labor.
AB  - OBJECTIVE: To identify risk factors for fever in labor. METHODS: A retrospective
      case-control study was conducted. Maternal sublingual temperature was measured
      every 2-4 hours during labor in 3109 of 3860 consecutive term parturients
      presenting from September 1992 through December 1993. Women who had fever (at
      least one recorded temperature of 38C or more, n = 72) during labor were compared
      with those who remained afebrile (n = 3037). Furthermore, a matched-pair case
      control study was conducted, involving 250 women at term who developed fever in
      labor and 250 controls matched for parity and duration of labor; all delivered
      between January 1989 and December 1993. A conditional multiple logistic
      regression analysis was used to identify independent risk factors for fever
      during labor. RESULTS: In the case-control study, fever was associated with
      epidural analgesia, nulliparity, and a long duration of labor. These three
      variables were also related among themselves. However, multiple regression
      analysis showed that all three variables were independently associated with
      maternal temperature. In the matched-pair study, epidural analgesia, rupture of
      membranes longer than 24 hours, latency phase exceeding 8 hours, and a
      temperature in the upper normal range (37.5-37.9C) at admission were independent
      risk factors for developing fever in labor. CONCLUSION: Epidural analgesia,
      duration of labor, and a long interval from rupture of membranes to delivery were
      independent risk factors for maternal fever in labor.

PMID- 7566849
TI  - Randomized trial of epidural versus intravenous analgesia during labor.
AB  - OBJECTIVE: To compare the effects of epidural analgesia with intravenous (IV)
      analgesia on the outcome of labor. METHODS: Thirteen hundred thirty women with
      uncomplicated term pregnancies and in spontaneous labor were randomized to be
      offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor.
      RESULTS: Comparison of the allocation groups by intent to treat revealed a
      significant association between epidural allocation and operative delivery for
      dystocia. However, only 65% of each randomization group accepted the allocated
      treatment. Four hundred thirty-seven women accepted and received meperidine as
      allocated, and they were compared with 432 women accepting epidural allocation.
      Significant associations resulted between epidural administration and
      prolongation of labor, increased rate of oxytocin administration,
      chorioamnionitis, low forceps, and cesarean delivery. Because of the high rate of
      noncompliance with treatment allocation, a multifactorial regression analysis was
      performed on the entire cohort, and a twofold relative risk of cesarean delivery
      persisted in association with epidural treatment. The impact of epidural
      treatment on cesarean delivery was significant for both nulliparous and parous
      women (risk ratios 2.55 and 3.81, respectively). Epidural analgesia provided
      significantly better pain relief in labor than did parenteral meperidine.
      CONCLUSION: Although labor epidural analgesia is superior to meperidine for pain
      relief, labor is prolonged, uterine infection is increased, and the number of
      operative deliveries are increased. A two- to fourfold increased risk of cesarean
      delivery is associated with epidural treatment in both nulliparous and parous
      women.

PMID- 7566851
TI  - The hemodynamic effects of maternal hypo- and hyperoxygenation in healthy term
      pregnancies.
AB  - OBJECTIVE: To evaluate the hemodynamic effects of maternal hypo- and
      hyperoxygenation in normal term pregnancy. METHODS: Ten healthy women between 35
      41 weeks' gestation were exposed to 10% oxygen in inspired air for 10 minutes
      and, after a 5-minute recovery period, to a stepwise increase in oxygenation with
      50 and 100% oxygen for 10 minutes. Maternal ventilation, hemodynamics, and
      oxygenation were assessed noninvasively, and maternal and fetal vascular
      responses were assessed with pulsed-wave color Doppler velocimetry. Computerized
      cardiotocography was used for fetal heart rate (FHR) analysis. RESULTS:
      Substantial maternal hypoxia was achieved and accompanied by a statistically
      significant rise in the maternal heart rate (from 89 +/- 11 to 104 +/- 16 beats
      per minute) and systolic blood pressure (from 123 +/- 13 to 131 +/- 13 mmHg).
      Doppler measurements demonstrated a statistically significant decline in the
      pulsatility index (PI) of the maternal internal carotid artery (from 1.8 +/- 0.3
      to 1.5 +/- 0.4) and an increase in the uterine artery PI (from 0.60 +/- 0.12 to
      0.72 +/- 0.13). Baseline FHR, heart rate variability, and Doppler velocimetry in
      the umbilical artery and the middle cerebral artery showed no statistically
      significant changes. Hyperoxia did not cause changes in the maternal circulation,
      but the FHR decreased significantly (from 142 +/- 12 to 133 +/- 11 beats per
      minute). CONCLUSION: Acute short-term hypoxia modifies the maternal circulation,
      suggesting redistribution of maternal blood flow, but exerts no detectable
      effects on the healthy fetus. Maternal hyperoxygenation induces no apparent
      adverse effects.

PMID- 7566852
TI  - Implications of idiopathic preterm delivery for previous and subsequent
      pregnancies.
AB  - OBJECTIVE: To describe the relationship between pregnancy complications and fetal
      outcome in first and second pregnancies, focusing on idiopathic and indicated
      preterm birth of singleton infants in either pregnancy. METHODS: Included in the
      study were 13,967 women in Denmark who gave birth to their first singleton infant
      in 1982 and a second infant in 1982-1987. Information on pregnancy and birth was
      obtained by linking the National Medical Birth Register and the National Register
      of Hospital Discharges, based on personal identification numbers. RESULTS: The
      risk of a preterm second birth in women with idiopathic and indicated preterm
      first birth did not differ significantly (15.2 and 12.8%, respectively). However,
      women with idiopathic preterm birth in the first pregnancy tended to repeat
      idiopathic preterm birth twice as often as women with indicated preterm birth
      repeated indicated preterm birth (11.3 versus 6.4%). Adjustment by logistic
      regression analysis for other risk factors for preterm birth did not influence
      the relative risk (6.0 before 32 weeks and 4.8 for 32-36 weeks) of a second
      preterm birth after a first preterm birth. Women with idiopathic preterm delivery
      in their first and second pregnancies gave birth to infants with lower birth
      weight than in previous or subsequent pregnancies. Emergency cesarean delivery in
      a first term pregnancy was a risk factor for subsequent idiopathic preterm birth.
      CONCLUSION: Idiopathic preterm birth is associated with emergency cesarean
      delivery at term in previous pregnancies and infants with lower birth weight in
      previous and subsequent pregnancies.

PMID- 7566853
TI  - Increased risk of placenta previa among women of Asian origin.
AB  - OBJECTIVE: To investigate the frequency of placenta previa among Asian women.
      METHODS: We conducted a population-based case-control study using Washington
      state birth certificate data from 1984-1987. Our study population included 810
      women with pregnancies complicated by placenta previa and 2917 randomly selected
      controls. Unconditional logistic regression was used to estimate odds ratios (OR)
      and their 95% confidence intervals (CI), and interaction terms were used to
      examine effect modification. Potential confounding by maternal age, gravidity and
      parity, maternal smoking during pregnancy, and a history of abortion or cesarean
      delivery was adjusted for in the analysis. RESULTS: The frequency of placenta
      previa during the study period was 3.3 per 1000 live births. Women of Asian
      origin were 86% more likely (OR 1.86, 95% CI 1.38-2.51) to have a delivery
      complicated by placenta previa than were white women. This association was
      stronger among women without a previous live birth (OR 2.51, 95% CI 1.57-4.01)
      than those who previously had experienced a live birth (OR 1.50, 95% CI 1.01
      2.25). CONCLUSION: Asian women residing in the United States are at increased
      risk of placenta previa. If confirmed by others, our results suggest that
      obstetricians should consider meticulous ultrasound evaluations during pregnancy
      to rule out the presence of placenta previa in Asian-American women.

PMID- 7566854
TI  - Outcomes of hospital-based managed care: a multivariate analysis of cost and
      quality.
AB  - OBJECTIVE: To determine the effects a hospital-based managed care intervention
      has on the cost and quality of care. METHODS: The intervention consisted of a
      CareMap and a nurse case manager. The CareMap contained both a critical path and
      a set of expected patient outcomes. The study population comprised all women who
      delivered by cesarean during the 18 months of the study and who were cared for in
      the maternity unit at a tertiary-level university hospital. The effects of the
      intervention were determined by comparing the after group with the before group
      in regard to length of stay and costs of care post-cesarean delivery, patient
      ratings of quality of care, and the physical recovery of the patients by
      discharge and 1 month later. RESULTS: After the implementation of hospital-based
      managed care, the average length of stay decreased 13.5% (0.7 days) and the
      average costs decreased 13.1% ($518). These decreases were statistically
      significant and remained so after controlling for co-morbid and complicating
      conditions. Patients perception of the quality of care increased from 4.26 to
      4.41 on a 1-5 scale, a statistically significant increase. In particular,
      patients believed that they had an increased level of participation in their
      care. The physical recovery scores obtained at discharge did not change.
      CONCLUSION: Hospital-based managed care can reduce resource use, length of stay,
      and cost associated with hospital care while maintaining or improving the quality
      of care. Whether these effects are reproducible and generalizable to other
      conditions should be addressed in future studies; the duration of these effects
      should also be examined.

PMID- 7566855
TI  - Elevated serum levels of vascular endothelial growth factor in patients with
      preeclampsia.
AB  - OBJECTIVE: To determine whether altered levels of vascular endothelial growth
      factor (VEGF) may be implicated in the pathogenesis of preeclampsia, and whether
      VEGF mediates the endothelial cell activation that is involved in the
      pathogenesis of the clinical syndrome. METHODS: In a cross-sectional study,
      maternal serum samples in late pregnancy (at the time of clinical disease) were
      collected from 78 nulliparous women. These subjects were subdivided into those
      with preeclampsia (n = 27), nonproteinuric pregnancy-induced hypertension (n =
      15), and normal pregnant women (n = 36). In a nested case-control study, in
      addition to samples taken before delivery, samples were obtained in early
      pregnancy (before clinical disease) and 24-48 hours postpartum from 12 of the
      patients with preeclampsia, 12 of those with nonproteinuric pregnancy-induced
      hypertension, and 12 of the normal pregnant subjects. Umbilical cord blood was
      sampled from 14 of the preeclamptic and 16 of the normal pregnant subjects. We
      measured VEGF levels in all samples using an immunofluorometric assay. RESULTS:
      In most samples collected before delivery, VEGF levels were below the lower limit
      of detection. However, the proportion of detectable levels was higher in the
      preeclampsia group (seven of 27) than in the normotensive group (one of 36, P <
      .05). The proportion in the nonproteinuric pregnancy-induced hypertension group
      (two of 15) did not differ significantly from the other groups. Levels in the
      patients with preeclampsia were not elevated before clinical disease. Levels of
      VEGF in umbilical blood samples were higher than in maternal venous blood,
      although there were no significant differences between groups. CONCLUSION: Serum
      VEGF levels were elevated in patients with preeclampsia, which suggests that the
      growth factor has a role in the endothelial cell activation that occurs in the
      disease.

PMID- 7566856
TI  - Umbilical plasma concentration of endothelin-1 in intrapartum fetal stress:
      effect of fetal heart rate abnormalities.
AB  - OBJECTIVE: To measure the umbilical plasma concentration of endothelin (ET)-1 in
      the presence of labor, fetal heart rate (FHR) abnormalities, and fetal hypoxia.
      METHODS: Umbilical and maternal plasma concentrations of ET-1 were measured in
      100 pregnant women at full-term deliveries (60 with vaginal delivery without
      induction and 40 with elective cesarean delivery without labor). We assessed the
      FHR pattern, measured umbilical blood gases and plasma concentration of
      vasopressin, and investigated the relationships between the umbilical vein-artery
      ET-1 concentration difference and these variables. RESULTS: The concentration of
      ET-1 in the umbilical vein was higher than in the umbilical artery and the
      maternal vein in all cases. The umbilical vein-artery ET-1 concentration
      difference (mean +/- standard error of the mean) was significantly greater in the
      vaginal delivery group (4.5 +/- 2.0 pmol/L) than in those delivered by elective
      cesarean (1.7 +/- 1.5 pmol/L) (P < .05). The umbilical vein-artery ET-1
      concentration difference was significantly greater when more than three episodes
      of severe variable decelerations occurred during the 30-minute period before
      delivery (7.0 +/- 2.0 pmol/L) than in the absence of any decelerations (1.6 +/-
      1.5 pmol/L) (P < .05). The umbilical vein-artery ET-1 concentration difference
      correlated positively with the umbilical arterial concentration of vasopressin (r
      = 0.45, P < .05) and negatively with the umbilical arterial oxygen pressure (r = 
      0.47, P < .05). CONCLUSION: In cases of vaginal delivery with FHR abnormalities
      and with fetal hypoxia, the fetoplacental concentration of ET-1 was increased.

PMID- 7566857
TI  - Use of the TDx-FLM assay in evaluating fetal lung maturity in an insulin
      dependent diabetic population. The Diabetes and Fetal Maturity Study Group.
AB  - OBJECTIVE: To assess the usefulness of the recently introduced TDx-FLM assay in
      managing pregnant women with diabetes. METHODS: Participating institutions were
      recruited from the 1993 and 1994 Society of Perinatal Obstetricians Diabetes
      Special Interest Group meetings. Study patients consisted of insulin-dependent
      diabetic women who had undergone transabdominal amniocentesis with assay of the
      fluid by the TDx-FLM method. Pertinent data were requested concerning pregnancy
      and respiratory outcomes of the corresponding neonates. RESULTS: Data from 261
      pregnancies at 13 institutions were collected. Eight of the 182 infants born
      within 4 days of amniocentesis developed respiratory distress syndrome (RDS);
      five of the eight infants with RDS required intubation, and all five had TDx-FLM
      values less than 70 mg of surfactant per gram of albumin. Three of the eight
      infants with RDS required hood oxygen only; two of these infants had TDx-FLM
      values at least 70 mg/g. Thirteen of 144 (9%) subjects who delivered within 4
      days of amniocentesis and for whom a TDx-FLM assay and phosphatidylglycerol level
      were both reported had a TDx-FLM level of at least 70 mg/g and a negative
      phosphatidylglycerol result. No infant with this combination of results developed
      RDS. Fifteen of the 40 patients who delivered more than 4 days after
      amniocentesis, with both tests available, had TDx-FLM values at least 70 mg/g and
      were phosphatidylglycerol negative. CONCLUSION: In infants of diabetic mothers,
      TDx-FLM values at least 70 mg/g were not associated with RDS requiring
      intubation. The TDx-FLM assay may be useful in determining the best time of
      delivery for pregnant patients with diabetes, especially in a situation in which
      the TDx-FLM assay is mature and the phosphatidylglycerol result is immature.

PMID- 7566858
TI  - Maternal and perinatal outcome of patients with preterm labor and meconium
      stained amniotic fluid.
AB  - OBJECTIVE: To determine the clinical significance of meconium-stained amniotic
      fluid (AF) observed at amniocentesis in patients with preterm labor. METHODS: A
      nested case-control study was constructed based on the color of AF during
      amniocentesis. Forty-five women admitted with preterm labor and meconium-stained
      AF were matched for gestational age at admission and compared with 135 women with
      preterm labor and clear AF. All AF samples were cultured for aerobic and
      anaerobic bacteria and mycoplasma. RESULTS: The rates of positive AF cultures for
      microorganisms, overall preterm birth (before 36 weeks), preterm birth before 32
      weeks, and clinical chorioamnionitis were all significantly higher in patients
      with meconium-stained AF than in those with clear AF (positive AF cultures, 38
      versus 11%, P < .001; preterm delivery before 36 weeks, 73 versus 41%, P < .001;
      preterm delivery before 32 weeks, 51 versus 17%, P < .001; and clinical
      chorioamnionitis, 22 versus 6%, P = .003). In contrast, no significant
      differences were observed between groups with respect to maternal age, gravidity,
      parity, abruptio placentae, placenta previa, fetal distress, cesarean rate, or
      puerperal morbidity. CONCLUSION: Patients with preterm labor and meconium-stained
      AF had higher rates of microbial invasion of the amniotic cavity, clinical
      chorioamnionitis, and premature deliveries than those with clear AF.

PMID- 7566859
TI  - The relationship between diet, activity, and other factors, and postpartum weight
      change by race.
AB  - OBJECTIVE: To identify the impact of dietary intake and activity level on
      postpartum weight change. METHODS: White (n = 121) and black (n = 224) women, 7
      12 months postpartum, participating in the Special Supplemental Feeding Program
      for Women, Infants, and Children were assessed for dietary intake, activity
      level, body weight, and other maternal characteristics. RESULTS: For both black
      and white women, the most important variables in predicting postpartum weight
      loss were pre-pregnancy weight, gestational weight gain, parity, and prenatal
      exercise. After these factors were controlled, race predicted that black women
      retained 6.4 lb more than white women. These results may be due to the finding
      that black women reported significantly higher mean energy intake (2039 versus
      1552 kcal, P < .001), higher percent fat in diet (41 versus 38%, P < .001), and
      significantly lower amounts of prenatal and postpartum activity. CONCLUSION:
      Higher energy intake and lower activity levels in black postpartum mothers
      compared with white mothers may contribute to the significantly higher rates of
      obesity found in black mothers. This study suggests the need for intervention
      strategies in the prenatal and postpartum periods to help those at risk of
      retaining weight gained during pregnancy.

PMID- 7566860
TI  - Urethral closure pressure and leak-point pressure in incontinent women.
AB  - OBJECTIVE: To examine the association between maximum urethral closure pressure
      and Valsalva leak-point pressure in women with genuine stress incontinence (GSI).
      METHODS: Fifty-six women with GSI were evaluated in a urodynamics laboratory.
      Maximum urethral closure pressure and vesical leak-point pressure were measured
      with multichannel urodynamic testing. The correlation coefficient and regression
      line were calculated. RESULTS: Forty subjects demonstrated a leak on Valsalva
      maneuver and, in these women, maximum urethral closure pressure and leak-point
      pressures were related significantly (r = 0.62, P < .001). The relationship was
      strongest between leak-point pressure up to 120 cm H2O and absolute vesical
      pressure with Valsalva rather than with a change in vesical pressure. The
      sensitivity of leak-point pressure for predicting low urethral pressure was 100%.
      CONCLUSION: There is a correlation between maximum urethral closure pressure and
      leak-point pressure that can provide useful information about incontinence in
      women.

PMID- 7566861
TI  - Gynecologic history of women with inflammatory bowel disease.
AB  - OBJECTIVE: To describe the gynecologic history of women with inflammatory bowel
      disease. METHODS: Questionnaires were sent to the 1000 women age 20-60 who had
      been hospitalized for inflammatory bowel disease at the Cleveland Clinic
      Foundation during 1989-1993. There were 692 responses, and those from 662 women
      who had undergone surgery for inflammatory bowel disease were analyzed. Of the
      117 women who had undergone hysterectomy, 85 responded to follow-up
      questionnaires. RESULTS: Three hundred sixty women had Crohn disease, 251 had
      ulcerative colitis, and 51 had inflammatory bowel disease of indeterminate or
      unknown type. Menstrual abnormalities were reported by 58%. Symptomatic vaginal
      discharge, reported by 40%, was more likely to occur in those with Crohn disease
      than with ulcerative colitis (odds ratio [OR] 2.09, 95% confidence interval [CI]
      1.47-2.99; P < .001). Infertility was reported by 25% of the women in this
      series. Abdominal pain with sexual intercourse (50% overall) was more common in
      women with Crohn disease than in those who had ulcerative colitis (OR 1.64, 95%
      CI 1.13-2.40; P = .01), but pain with penetration (55% overall) did not differ
      statistically by type of inflammatory bowel disease. Half of the women reported
      the loss of pleasure or desire for sex. Ovarian cysts had been diagnosed in 39%
      of women and resulted in surgical treatment in 57% of these. One hundred
      seventeen women (18%) had undergone hysterectomy, 52 (44% of total) at age 35 or
      younger. CONCLUSION: Gynecologic conditions are common in women with inflammatory
      bowel disease, including menstrual abnormalities, vaginal discharge, infertility,
      and gynecologic surgery. All physicians providing care for women with
      inflammatory bowel disease should be familiar with the frequency and nature of
      concurrent gynecologic conditions.

PMID- 7566862
TI  - A hook-traction technique for Norplant removal.
AB  - We describe a simple technique to facilitate the removal of difficult-to-remove
      Norplant implants. Through a standard skin incision for Norplant removal, the
      fibrous capsule surrounding the implant is secured using either a dermatologic
      skin hook or a 25-gauge hypodermic needle fashioned into a hook with a hemostat.
      Traction is applied to bring the fibrous sheath into the incision site, where the
      implant tip is dissected free using a scalpel. The precisely localized
      countertraction afforded by this technique provides increased accuracy and speed
      for the removal of difficult-to-extract implants. Tissue trauma is minimized and
      the need to extend the skin incision is reduced.

PMID- 7566863
TI  - A new device for collecting cord blood.
AB  - Safe sampling of cord blood can reduce the risk of exposure to infectious agents
      by obstetric personnel. We developed a new device for collecting umbilical cord
      blood. Using a modified closed-cup instrument, gravity drainage within the sealed
      device allows for guarded-needle vacuum tube blood collection. The mean (+/-
      standard deviation) volume of blood collected with the device was 6.1 +/- 3.1 mL.
      Adding heparin into the device increased the volume collected by approximately 2
      mL. The diameter and length of the cord were also related to the amount obtained.
      Only two of 122 samples (1.6%) had less than 1 mL of blood. The introduction of a
      closed container, umbilical cord sampling device offers a clear potential for
      risk reduction, particularly the risk of needle-stick injuries but also direct
      blood contamination. The device is simple to use, offers easy and safe disposal,
      and can be operated by physicians or nurses.

PMID- 7566864
TI  - Rewarding medical student teaching.
AB  - Scholarship in academic medicine includes the discovery of new knowledge as well
      as the integration, application, and teaching of existing knowledge. Although all
      components are vital, the rewards for each may vary considerably. Many medical
      educators have recommended that the teaching of medical students be given the
      same level of esteem traditionally awarded to research and patient care, and that
      the same level of excellence must be expected from teachers as from researchers
      and clinicians. Common facets of three successful reward systems in place include
      documenting quality as well as quantity; rewarding all excellent teachers, not
      just "the best"; and publicizing the rewards to students, peers, and
      administrators.

PMID- 7566865
TI  - The problem of the type II statistical error.
AB  - OBJECTIVE: To determine if type II statistical errors (also known as beta errors)
      are a common problem in published clinical research. METHODS: Type II statistical
      errors occur when sample sizes are too small to show an effect of treatment, even
      when an effect truly exists. Searching the Medline data base, we identified ten
      meta-analyses published during 1986-1994 in the American Journal of Obstetrics
      and Gynecology, Obstetrics and Gynecology, and The Journal of Reproductive
      Medicine. Meta-analyses were used as sources of component or individual studies
      for the following reason: When small component studies have negative findings
      that differ from the overall conclusions of the meta-analysis, the component
      studies may have type II statistical errors. RESULTS: We found that only 6.5% (15
      of 231) of component studies provided any documentation that power calculations
      to determine sample sizes had been done a priori (before) the research began.
      Thus, many of these component studies with findings of no treatment effect may
      have had type II errors because of too-small sample sizes. When stratifying the
      component studies by year of publication, we found that 7.9% (14 of 178) of
      studies published in the 1980s and 1990s had any documented evidence of a priori
      power calculations. In the 1960s and 1970s, only one of 53 component studies had
      documented evidence of power calculations. CONCLUSION: To ensure that truly
      effective treatments are introduced into clinical practice as quickly as
      possible, we believe that a priori power calculations should always be done in
      quantitative clinical research.

PMID- 7566866
TI  - Prospects for a vaccine against human papillomavirus.
AB  - OBJECTIVE: To summarize existing data regarding the feasibility of developing
      strategies for prophylactic and therapeutic vaccination against human
      papillomavirus (HPV) infection. DATA SOURCES: We used the Medline data base and
      reference lists of articles to identify English-language papers that evaluate
      strategies for prophylactic and therapeutic vaccination against HPV infection.
      METHODS OF STUDY SELECTION: Our search uncovered several reports of systems that
      produce recombinant HPV major capsid proteins as antigens for biochemical,
      molecular, and immunologic studies and investigations that evaluate cell-mediated
      immune responses to HPV-induced, tumor-associated peptides. DATA EXTRACTION AND
      SYNTHESIS: Recombinant HPV major capsid proteins, which self-assemble into virus
      like particles, are produced in quantity, mimic the conformation of native
      virions, react with neutralizing antibodies, and are type-specific. Human
      papillomavirus early viral peptides induce cytotoxic T lymphocyte responses that
      retard tumor progression and protect against tumor development after challenge in
      animal models. CONCLUSIONS: Recombinant papillomavirus virus-like particles are
      highly antigenic, protective in animal models, lack potentially carcinogenic
      viral DNA, and are, therefore, ideal candidates for a prophylactic vaccine
      against HPV infection. Immunization with HPV tumor peptides may be beneficial in
      tumor prevention, regression, and rejection. Vaccines against HPV infection can
      be important in reducing the incidence of cervical dysplasia and carcinoma
      worldwide, particularly in developing countries.

PMID- 7566867
TI  - The effect of maternal obesity on the accuracy of fetal weight estimation.

PMID- 7566868
TI  - Screening and treatment of asymptomatic bacteriuria of pregnancy to prevent
      pyelonephritis: a cost-effectiveness and cost-benefit analysis.

PMID- 7566869
TI  - Good practice with endometrial ablation.

PMID- 7566871
TI  - What's that smell?

PMID- 7566870
TI  - Combined continuous hormone replacement therapy: a critical review.

PMID- 7566872
TI  - Avoid injury in confined spaces.

PMID- 7566873
TI  - Strong, balanced muscles can prevent CTS.

PMID- 7566874
TI  - Targeted medical care reduces lost-time injuries.

PMID- 7566876
TI  - Peroxidase activity and cell differentiation in developing salivary glands of the
      rats.
AB  - Peroxidase (PO) activity-positive cells were found to develop in both the
      sublingual and submandibular glands of the rat on day 19 of gestation. The PO
      activity in the nuclear envelope (NE), endoplasmic reticulum (ER), Golgi
      apparatus (G) and secretory granules (SG) of these cells were enhanced day by
      day. However, no PO activity was detected in the parotid gland on the same day.
      In the parotid gland PO-positive cells were detected first on postnatal day 1.
      After birth the PO activity in the SG of both the sublingual and submandibular
      glands gradually diminished in intensity and disappeared, whereas the activity
      persisted in the parotid gland. From postnatal day 1 to 14, the NE and ER of the
      cells in the parotid and sublingual glands exhibited intense PO activity, while
      cells containing mucous SG appeared. The cells were identified as mucoserous
      acinar cells. These mucoserous cells later differentiated into different cell
      types: serous cells in the parotid gland and mucous cells in the sublingual
      gland. As the submandibular gland developed, PO activity-positive serous cells
      also differentiated into mucoserous cells and the activity in the G and SG
      disappeared. The parotid, sublingual and submandibular glands of perinatal rats
      have clearly showed varied growth, with the advent processes of PO activity and
      cell differentiation, whereas PO activity in the G concomitantly occurred with SG
      activity.

PMID- 7566877
TI  - An anatomical analysis of the dorsoventral relationship between the sacral plexus
      and the pudendal nerve in man by use of computer aided three-dimensional
      reconstruction.
AB  - In order to investigate the dorsoventral relationship between the sacral plexus
      and the pudendal nerve in man, morphological examination was performed on one
      pelvic half of a male cadaver. The second and third spinal nerves were removed en
      bloc and sectioned serially for three-dimensional reconstruction imaging of the
      selected sections. Comparison of the sequential images revealed that the root of
      the pudendal nerve is first situated ventral to the caudal root of the sacral
      plexus, and that the former and the latter are shifted cranialward and
      caudalward, respectively, at the point of exit from the second anterior sacral
      foramen.

PMID- 7566875
TI  - Morphology of the nerve terminals of laryngeal muscles in the Japanese monkey
      (Macaca fuscata).
AB  - Laryngeal muscles, namely, the cricothyroid (CT), lateral crico-arytenoid (LCA),
      thyrio-arytenoid (TA), posterior crio-arytenoid (PCA), interarytenoid (IA)
      muscles, of Japanese monkeys (body weight, 4.4-8.3 kg; 3-10 years old, male) were
      examined histologically and by light and scanning electron microscopy. The
      diameter of muscle fibres with nerve terminals in the CT of the Japanese monkey
      was larger than that of other laryngeal muscles. However, the areas of nerve
      terminals varied among laryngeal muscles. The mean diameters of nerve terminals
      of the CT and PCA were large and basically resembled those of other laryngeal
      muscles. They contribute mainly to maintenance of phonation which the adductor
      muscles contribute mainly to postural adjustments of the cartilage. The
      differences in features of nerve terminals of each muscle suggest the CT and PCA
      may contribute mainly to the frequency or pitch of voice and intensity of the
      voice during vocalization and to respiration.

PMID- 7566878
TI  - Growth pattern of the maxillary sinus in orang-utan based on measurements of CT
      scans.
AB  - The postnatal growth of the maxillary sinus was analyzed in 20 male and 20 female
      skulls of orang-utan (Pongo satyrus borneensis) in 5 age steps. Coronal CT scans
      were carried out of all skulls using a computed tomograph Siemens SOMATOM DR. The
      distances between the CT scans were always 4 mm. The outline of the maxillary
      sinus was surrounded on the CT scans with a planimeter and then the volumes were
      calculated. Using a growth model introduced by Fanghanel (1974), growth functions
      for the volume measurements for male and female animals were calculated
      separately. The growth curves showed a particular course, which was characterized
      by a quick rise until the age of 15 years. After the age of 20 years the curves
      for females orang-utan became gradually flat. At the age of 21 to 23 years the
      confidence intervals of the growth curves for male and female orang-utan began to
      drift apart, indicating the appearance of a sexual dimorphism. Using the
      basicranial length as an indicator of skull size, it becomes evident, that the
      sexual difference in the maxillary sinus' volume is probably based on the fact,
      that the maxillary sinus' volume of the male orang-utan increases further on
      following a common growth pattern.

PMID- 7566879
TI  - Development of the spinous process of the second thoracic vertebra of the mouse
      in the late fetal and early postnatal period.
AB  - The bony spinous process of T2 in certain inbred strains of the mouse is variable
      in size or in some cases absent. The development of this process has been
      investigated in histological sections of CBA, C57BL and tk/tk mice between birth
      and 14 days. The spinous process is shown to be modified in shape and size late
      in development.

PMID- 7566880
TI  - Variations in the numbers of phalangeal bones in the four-toed salamander,
      Hynobius tenuis (Amphibia: Hynobiidae), from two localities in Toyama Prefecture,
      Central Japan.
AB  - Variations in the numbers of phalangeal bones in the fingers (I to IV) and toes
      (I to V) of specimens of Hynobius tenuis collected from two localities
      (Ashikuraji and Arimine) in Toyama Prefecture, Central Japan, were recorded. In
      the case of fingers of fore limbs, eight phalangeal formulas were distinguished,
      and in the case of toes of hind limbs, ten phalangeal formulas were recognized.
      In the fingers of specimens from Ashikuraji, the predominant formulas were 2-2-3
      2 (40%) and 2-2-3-1 (32%). In specimens from Arimine, 2-2-3-2 was predominant
      (75%). In toes, the predominant formula was 2-2-3-2-0- (96%) for Ashikuraji and
      71% for Arimine. The maximal number of phalangeal bones, 2-2-3-3-2, found in the
      toes of specimens from Arimine seems to represent the fundamental formula in
      hynobiid salamanders. The predominant formula, 2-2-3-2-0-, observed in the two
      populations may have been derived from the fundamental formula by degeneration of
      the phalangeal bones in the fourth and the fifth toes. The reason why phalangeal
      bones were degenerated in this species is discussed from an ecological viewpoint
      of body growth.

PMID- 7566882
TI  - Culture-specific health care: a goal of nursing.

PMID- 7566881
TI  - The winds of change.

PMID- 7566884
TI  - A new grad's perspective.

PMID- 7566883
TI  - Restructuring.

PMID- 7566885
TI  - Our future must build on our past.

PMID- 7566886
TI  - Home care: what more could an educator want?

PMID- 7566887
TI  - Ethics with a capital C: or caring, ethics as a lived experience.

PMID- 7566888
TI  - After health care reform: now what?

PMID- 7566889
TI  - Nursing makes the grade in report cards.

PMID- 7566890
TI  - Telemedicine.

PMID- 7566891
TI  - LPN to RN.

PMID- 7566893
TI  - Tulsa sexual assault nurse examiners program.

PMID- 7566894
TI  - A thoughtful pause.

PMID- 7566892
TI  - Cultural diversity: you make a difference.

PMID- 7566895
TI  - A modern perspective of nursing.

PMID- 7566896
TI  - Pain control: an on-going problem.

PMID- 7566897
TI  - Alcohol and drug testing ... balancing the interests of employers and employees.

PMID- 7566898
TI  - The Glenn A. Fry Award Lecture. Early losses of visual function in glaucoma.
AB  - Getting back to the questions raised by Dr. Enoch 12 years ago, I believe that we
      have made significant progress in the early psychophysical detection of glaucoma
      and that we are either on the right track or considerably closer to it. The
      continuing progress in conventional automated perimetry has improved the overall
      quality of visual field testing in the ophthalmic community, as well as providing
      standardization and state-of-the-art analysis procedures for everyone. We have
      certainly not solved the problem of early detection of glaucoma, but we now have
      more sensitive procedures that are available for existing clinical
      instrumentation. SWAP has clearly shown that it is able to detect glaucomatous
      losses several years before they are evident by conventional automated perimetry,
      and results from the other test procedures mentioned earlier are also very
      encouraging. Thus, although we may not yet have the pot of gold, we have been
      able to pick up a few valuable nuggets along the way. This leads me to believe
      that the current approaches are on the right track. However, Dr. Enoch's message
      should also serve to remind us that there are few panaceas for early detection of
      functional loss in glaucoma. Our progress to date has been influenced by our
      greater understanding of the properties of visual mechanisms and the
      pathophysiology of glaucoma. It has also been driven by clever and innovative
      approaches and new test procedures, as well as advances in technology. However,
      it has also been based on a considerable amount of research effort in the form of
      long-term prospective longitudinal studies of large populations of normal
      observers, patients with various stages of glaucomatous damage, and patients at
      risk of developing glaucoma. Answers to all of the issues pertaining to the
      ultimate clinical value of psychophysical procedures for early detection of
      glaucoma do not come quickly, but they are of vital importance to ocular health
      care. I hope that my brief discussion of new developments in psychophysical
      detection of glaucoma has convinced you that significant progress has been made,
      and that some of you will be motivated to join in this important research
      endeavor.

PMID- 7566899
TI  - Vision thresholds from psychometric analyses: alternatives to probit analysis.
AB  - Vision scientists and clinicians regularly obtain measures of vision and
      determine a person's vision threshold by choosing one of numerous methods of
      analysis. Analytical methods differ in their presumptions about the measures, in
      their complexity and in the ease of obtaining the threshold estimate. In light of
      these differences among so-called methods of psychometric analysis, the question
      is, "Do various analytical methods provide essentially equivalent vision
      threshold estimates or are there consequential differences that require
      consideration?" Measures of visual acuity, motion processing, and texture
      processing were obtained from 20 subjects. Each set of measures was analyzed by
      five psychometric methods: Logit Analysis, Normit Analysis, and linear regression
      of z-score transformed, logit transformed and untransformed probabilities vs.
      stimulus strength. The resulting thresholds were compared to the threshold
      obtained from Probit Analysis, which was used as a reference or "gold standard."
      Thresholds from the procedures were remarkably similar to those from Probit
      Analysis. In addition, examination of the speed of the procedures revealed that
      Probit Analysis was up to 10 times slower than some of the others. Considering
      the similarity of thresholds, the speed of computation, and the ease of
      implementation, Logit and Normit Analyses especially provide effective
      alternatives to the current gold standard, Probit Analysis, for the estimation of
      psychometric thresholds. In addition, z-score, logit, and linear regressions also
      produced unbiased threshold estimates under many circumstances, but the latter
      method should be applied with some caution.

PMID- 7566900
TI  - Blink-induced motion of a gas permeable contact lens.
AB  - The blink-induced dynamics of a gas permeable contact lens are analyzed. The lens
      is considered to be a planar, circular, porous disk of specified permeability.
      Specifically, this work investigates the effects of those variables that
      characterize the porous nature of the lens such as the permeability and thickness
      of the lens and the effective slip coefficient. The equations governing the
      dynamics of the tear film and of the lens are solved subject to physical
      constraints that limit the duration and extent of the lens motion. The motion of
      a permeable contact lens can be controlled by a proper choice of the lens
      material microstructure. Analysis of the results indicates that the motion of the
      lens is enhanced by lower values of the slip coefficient and higher values of the
      permeability, independent of the lens thickness. In addition, thicker lenses as
      well as thicker tear films cause the lens to squeeze faster and to slide slower.

PMID- 7566902
TI  - Ray vector fields and representation of thin spherocylindrical lenses.
AB  - PURPOSE: To introduce the concept of the ray vector field and apply it to a
      problem in ophthalmic optics. METHODS: Matrix and linear algebra are used to
      relate ray vector fields and a representation of thin spherocylindrical lenses.
      RESULTS: Equations were derived relating ray vector fields and a particular
      coordinate system recommended previously. The method is illustrated with a simple
      example from ophthalmic optics, namely, addition of spherocylindrical lenses. We
      also illustrate the method by considering two spherocylinders separated by a
      distance. CONCLUSIONS: Ray vector fields are intuitively simple and can be used
      to solve complex ophthalmic optics problems.

PMID- 7566901
TI  - Effect of location and orientation uncertainty on r.m.s. contrast sensitivity
      with and without spatial noise in peripheral and foveal vision.
AB  - PURPOSE: We studied the effect of spatial location and orientation uncertainty on
      r.m.s. contrast sensitivity with and without external spatial noise in peripheral
      and foveal vision. METHODS: In the first experiment we used a small circular
      cosine grating with randomized location embedded in spatial noise and exposed for
      33 to 533 ms in peripheral vision. In the second experiment, performed with and
      without noise, we varied the randomization range of stimulus location in a foveal
      search task with free eye movements and an unlimited exposure time. In the third
      experiment we used a vertical cosine grating exposed for 500 ms and varied the
      randomization range of aperture orientation in the fovea with and without noise.
      RESULTS: Uncertainty of spatial location had no effect on r.m.s. contrast
      sensitivity in the periphery or fovea. However, sensitivity decreased with
      increasing randomization range of aperture orientation in the fovea. CONCLUSIONS:
      Uncertainty of spatial location had no effect because the accuracy of positional
      information is inherently poor in peripheral vision, whereas in the fovea the
      effect of location uncertainty was compensated for by searching eye movements.
      Randomization of aperture orientation reduced contrast sensitivity in the fovea
      because in this case the effect of randomization could not be compensated for.

PMID- 7566903
TI  - Refractive variation during autorefraction: multivariate distribution of
      refractive status.
AB  - The refractive variation of a sample of 106 university students (63 females and
      43 males) studying optometry was examined by means of autorefraction. Stereo-pair
      scatter plots in Euclidean three-dimensional h-space are used to illustrate the
      nature of the spread or distribution of data measurements found in particular
      subjects. A wide variety of different distributions were observed ranging from
      tightly to loosely clustered arrangements of measurements. Some aspects of
      departure from multivariate normality, including outliers (atypical measurements
      in a sample) and polymodal or multimodal distributions, are demonstrated.
      Outliers appear to be possible anywhere in the space of the scatter plots,
      although outliers may be more common in the region of h-space corresponding to
      transitory increases in accommodation. Multimodal distributions may be indicative
      of changes in ocular fixation during autorefraction or may reflect accommodative
      or other anomalies. Other departures from multivariate normality such as kurtosis
      and skewness are also of importance when attempting to form an understanding of
      variation of refractive state. Measurements made on an artificial or test eye
      showed very tight clusters in h-space. This suggests that the autorefractor
      itself contributes little to the variation observed during autorefraction of an
      eye.

PMID- 7566904
TI  - Field of view and equivalent viewing power of near-vision telescopes.
AB  - There are often substantial differences in linear field of view (FOV) and
      equivalent viewing power (EVP) when a distance telescope is either fitted with an
      objective lens cap or adjusted in length to focus for near vision. In addition,
      larger differences in linear FOV are found for Galilean than for Keplerian
      telescopes of similar magnification and EVP. Simple formulas are presented here
      that make use of EVP as a factor for calculating the linear FOV ratio between the
      two methods of converting distance Galilean and Keplerian telescopes for near
      vision. Examples are provided to illustrate the clinical application of these
      formulas. The information presented here may be helpful when making
      recommendations concerning the most appropriate method of converting a telescope
      for near vision.

PMID- 7566905
TI  - Mechanisms of pathogenesis in diabetes mellitus.
AB  - Diabetes mellitus is a syndrome of complex etiology and pathogenesis involving
      abnormal insulin synthesis, release, binding, and target cell activation. These
      are manifested differently in the two most common forms of this disease: insulin
      dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus
      (NIDDM). Although there still remains much to be discovered to complete our
      understanding, significant contributions have been made in the last few years by
      molecular genetics and immunology. This paper reviews many of these facets in
      contrast to others, which deal primarily with issues of management.

PMID- 7566906
TI  - A note on the accuracy of inexpensive light meters for measuring luminous
      transmittance.

PMID- 7566907
TI  - Arthroscopic anatomy of the shoulder.
AB  - The importance of a thorough knowledge of regional anatomy in any surgical
      discipline cannot be overemphasized. This is particularly true for the
      orthopedist as arthroscopic procedures continue to evolve with our increased
      understanding of shoulder pathology and as we attempt to improve patient
      outcomes. Surface and bony anatomy allow the arthroscopist to infer the location
      of the glenohumeral joint and subacromial space. Proper portal placement allows
      access to these regions without risk of neurovascular, tendon, or articular
      injury. Glenohumeral and subacromial anatomy can be clearly seen arthroscopically
      with many normal variants. Knowledge of normal shoulder anatomy allows the
      orthopedic surgeon to safely and successfully treat pathologic conditions.

PMID- 7566908
TI  - Arthroscopic evaluation and treatment of shoulder instability.
AB  - The use of the arthroscope for shoulder instability has improved our
      understanding of normal and pathologic shoulder anatomy. We must emphasize,
      however, that the majority of shoulder problems can be accurately diagnosed with
      a thorough history and good physical examination. The arthroscope is helpful,
      however, to confirm a clinical diagnosis or assist in making a diagnosis in
      difficult or complex pathologic findings. Further, as our surgical techniques and
      understanding of shoulder instability improve, more pathologic entities about the
      shoulder become amenable to arthroscopic surgical procedures. We must emphasize
      that most of these arthroscopic procedures are technically demanding and
      significant learning curves exist. These procedures should be undertaken only by
      physicians who have excellent arthroscopic skills and are comfortable recognizing
      normal and pathologic arthroscopic anatomy of the shoulder.

PMID- 7566909
TI  - Arthroscopic treatment of impingement syndrome.
AB  - The clinical relevance of subacromial pathology has been recognized for most of
      this century. More recently, the term "impingement syndrome" has been used to
      refer to a spectrum of subacromial pathology, ranging from tendinitis to rotator
      cuff tearing, and is probably the most common cause of shoulder pain. Increased
      experience with arthroscopy and advances in arthroscopic instrumentation have led
      to the widespread use of arthroscopy to treat impingement syndrome. This
      evolution in treatment will undoubtedly add to our understanding of the
      pathology. The indications for surgical treatment and the results have not
      changed significantly. The often proposed theoretical advantages of arthroscopy
      are being investigated.

PMID- 7566910
TI  - Arthroscopic evaluation and treatment of the rotator cuff.
AB  - Arthroscopy has improved our diagnostic assessment of rotator cuff disease,
      especially in understanding patterns of articular surface partial-thickness
      tears. Arthroscopic subacromial decompression is a proven and reliable
      alternative to open acromioplasty. Despite continued controversy, most partial
      thickness rotator cuff tears may be satisfactorily treated by arthroscopic
      debridement and decompression. The role for debridement and decompression without
      repair for full-thickness rotator cuff tears seems less than initially suggested,
      as several recent independent studies have documented results inferior to open
      repair. Arthroscopically assisted mini-open repair of small, full-thickness
      rotator cuff tears is a reliable procedure. Arthroscopic repair appears
      promising, but is not yet well enough documented to be considered a standard
      treatment.

PMID- 7566911
TI  - Arthroscopy of the acromioclavicular joint.
AB  - For many years the Mumford procedure or open resection of the distal clavicle has
      been the procedure of choice for the treatment of recalcitrant acromioclavicular
      joint pain. With advancement in shoulder arthroscopy and bursoscopy, arthroscopic
      resection of the distal clavicle can reproduce similar excellent results,
      avoiding some of the risks of the open procedure, including joint instability and
      muscle weakness. The arthroscopist can select from two approaches, a direct or
      superior approach or the indirect or subacromial approach. Both approaches are
      effective if the resection is performed in a systematic fashion and the amount of
      resection measured post-operatively. The authors have attempted to describe the
      pertinent anatomy of the acromioclavicular joint, clinical indications, and
      surgical technique for arthroscopic resection of the distal clavicle.

PMID- 7566912
TI  - Arthroscopic anatomy of the elbow.
AB  - Elbow arthroscopy is becoming a mainstream orthopedic procedure. Through multiple
      portals, a thorough evaluation of the entire elbow joint is possible. However, an
      understanding of normal arthroscopic anatomy is essential for orientation and
      alienation of pathologic processes.

PMID- 7566913
TI  - Arthroscopic removal of loose bodies of the elbow.
AB  - Arthroscopy of the elbow has proven to have a diagnostic and therapeutic benefit.
      Removal of loose bodies and a thorough evaluation of associated intra-articular
      pathologies are possible without arthrotomy. The authors have found this
      procedure to be safe and effective in the treatment of loose bodies of the elbow
      and other associated pathologies.

PMID- 7566914
TI  - Arthroscopic treatment for osteoarthritis of the elbow.
AB  - Arthroscopy has taken on a valuable role in the management of osteoarthritis of
      the elbow. Most patients have loose bodies, of which some are not detected on
      radiographs are all effectively removed arthroscopically. Excision of osteophytes
      from the olecranon and the coronoid as well as from the olecranon and coronoid
      fossae (to re-create the original fossae) eliminate the painful impingement at
      the extremes of motion that is typical of this condition. Release of contracted
      capsular tissues can also be performed at the same time by stripping the capsule
      from the humeral attachments. As with all arthroscopic procedures, one must be
      highly respectful of the possible complication of nerve injury, and experience
      with this technique combined with a thorough knowledge of the anatomy and the
      underlying pathology are essential for its safe use.

PMID- 7566916
TI  - Arthroscopic treatment of triangular fibrocartilage tears.
AB  - Lesions of the TFCC are more frequently implicated as a cause of ulnar-sided
      wrist pain. Accurate diagnosis of TFCC pathology must be based on a thorough
      history and physical examination. Imaging modalities of particular use include
      plain radiographs, triple compartment arthrography, and MR imaging. The most
      sensitive and accurate diagnosis of the extent as well as the clinical
      significance of intra-articular pathology on the ulnar side of the wrist is by
      means of the arthroscope. With the advent of smaller and more elaborate
      arthroscopic instrumentation, the ability to perform arthroscopic surgery on the
      TFCC has dramatically increased over the past decade. The present arthroscopic
      treatment of traumatic central and radial lesions consists of debridement of
      unstable flaps, whereas dorsal and ulnar-sided lesions can be directly repaired.
      Centrally located degenerative perforations can be debrided in conjunction with
      an arthroscopic wafer procedure on the distal ulna.

PMID- 7566915
TI  - Arthroscopic anatomy of the wrist.
AB  - A good working knowledge of the intra-articular anatomy of the wrist is essential
      to perform arthroscopy. The authors present a detailed description of all
      pertinent structures that may be seen during a radiocarpal and midcarpal
      arthroscopic examination.

PMID- 7566919
TI  - Stabilization of the fractured scaphoid under arthroscopic control.
AB  - All surgical procedures for the scaphoid are technically demanding. Nonunion,
      however, is associated with predictable adverse consequences, and union is
      predicated on effective fracture immobilization. The arthroscopically assisted
      approach to scaphoid fractures provides the combined advantages of internal
      fracture fixation and minimally invasive surgical technique (Fig. 5). Patients
      are receptive to the approach, and the new fixation device has proven to be
      extremely effective in the first 5 years of clinical usage.

PMID- 7566920
TI  - Arthroscopy of the distal radioulnar joint.
AB  - Arthroscopy of the distal radioulnar joint is challenging. Its indications are
      evolving. When the experienced hand surgeon believes that the procedure is
      justified, unusual discoveries may be made. Patients with distal radioulnar joint
      pain who remain a diagnostic challenge before arthroscopy may sometimes be helped
      by the results of arthroscopy of this small joint.

PMID- 7566918
TI  - Arthroscopic reduction and internal fixation of distal radius fractures.
AB  - Despite recent advances in the treatment of complex distal radius fractures,
      problems of stiffness, carpal instability, and posttraumatic arthritis remain in
      a significant number of cases. Associated soft-tissue and ligamentous injuries
      are being recognized with increasing frequency. Arthroscopic reduction and
      internal fixation not only allow for anatomic reduction of the distal radius
      fracture with minimal surgical trauma, but provides a valid diagnostic and
      treatment alternative for the often missed associated injuries.

PMID- 7566917
TI  - Arthroscopy for carpal instability.
AB  - Arthroscopy of the wrist has become a valuable adjunct in the evaluation and
      treatment of injuries to the wrist. Arthroscopic visualization aids in the
      diagnosis and management of carpal instability, triangular fibrocartilage complex
      tears, and certain fractures. Arthroscopically assisted stabilization and
      reconstruction allow rapid rehabilitation and functional recovery.

PMID- 7566921
TI  - Diagnostic imaging and arthroscopy for chronic wrist pain.
AB  - This article discusses a current overview of the diagnostic imaging techniques
      available to the orthopaedic surgeon trying to establish an etiology of chronic
      wrist pain. A discussion on the use of arthroscopy in conjunction with or as a
      replacement for these imaging techniques is also presented. A discussion of the
      advantages and disadvantages of each of these techniques is provided to try to
      aid the reader in establishing a cost-effective and efficient treatment algorithm
      for these difficult diagnostic dilemmas.

PMID- 7566922
TI  - Carpal tunnel syndrome. Etiology and endoscopic treatment.
AB  - Carpal tunnel syndrome involves classic symptoms of numbness and paresthesias in
      the radial three and one-half digits, most frequently nocturnal, with pain
      associated with this anatomic distribution. Thenar weakness and autonomic
      dysfunction occurs late in these patients and are usually seen in advanced cases.
      The wrist flexion test and local percussion sensitivity tests done on physical
      examination can be helpful in determining and confirming the diagnosis of carpal
      tunnel syndrome. The likelihood that operative treatment will be required for
      resolution of symptoms is heightened if the patient is involved in daily manual
      repetitive activities of the hand or wrist. Surgical decompression can be
      accomplished by either a limited open or new endoscopic carpal tunnel release
      techniques. Currently, the advantages and disadvantages present in both
      procedures and careful controlled studies conducted in a prospective and
      randomized fashion will be required to further delineate the indications for
      either procedure. Carpal tunnel release remains an operative procedure with the
      most predictable outcome with relief of symptoms for the patient.

PMID- 7566923
TI  - ONA provides guidance on RN's dilemma. On April 27, 1995 the ONA House of
      Delegates overwhelmingly adopted the following position statement on the nurse's
      role in the Death with Dignity Act. Oregon Nurses Association.

PMID- 7566924
TI  - Registered nurses liable for delegated tasks.

PMID- 7566925
TI  - Student nurse joins RN battle.

PMID- 7566926
TI  - Oregon nurses campaign for better health. Campaign launches free Southeast
      immunization clinic.

PMID- 7566927
TI  - Speaking on behalf of nurses. Patients before profits.

PMID- 7566928
TI  - Speaking on behalf of nurses. Speaking on behalf of AURN.

PMID- 7566929
TI  - [Use of taxol in the management of malignant tumors].
AB  - Taxol is a novel cytostatic agent which inhibits the depolymerisation of
      microtubulin. The stabilization of this important substance leads to cellular
      arrest and consecutively apoptosis. Accordingly, taxol is capable to influence
      neoplastic growth in several malignancies. At present the following standard
      regimen is recommended: 175 mg/m2 taxol in a 3-hour i. v. infusion following
      corticosteroid + diphenhydramine + cimetidine premedication. Its antitumour
      activity has been proved especially in advanced ovarian and breast cancer.
      Encouraging results have been reported in various bronchial, testicular
      malignancies, lymphomas and leukemias. Clinical investigations in several other
      malignancies are ongoing.

PMID- 7566930
TI  - [Quality of life of post-colostomy patients].
AB  - The psychosomatic care of patients after surgical treatment must comprise the
      analysis of quality of life with colostomy. Five different parameters were
      assessed of 100 colostomy patients. Sixty-one percent of our patients had skin
      irritation problems. Twenty-eight patients applied regular irrigation. Seventy
      two percent of these had daily motions, 20% had bidaily, the remaining 8% had
      irregular bowel movements. Seventeen percent of the nonirrigating patients
      observed very irritating fecal discharge around the stoma. Embarrassing noises
      concomittant with bowel movements were observed by 42% and 45% struggled with bad
      odors. Irrigating patients had hardly any of these problems. For 65% of the
      patients the idea of having a colostoma meant the greatest psychological burden
      before the operation. The stress situation culminated in the immediate
      postoperative period in 10%. Forty percent of those asked were seriously worried
      about the reaction of their social environment. In 65% a significant decrease of
      social relations could be observed. Sixteen percent reported an increased social
      activity after colostomy had been performed. Sixty percent admitted considering
      the option of suicide at least once. Thirty-five percent revealed to have any
      kind of sexual problems after colostomy. Eight of our 100 colostomy patients
      experienced serious adverse reactions from their family members. In eighty
      percent of the cases family members showed great sympathy although they acted
      naively. The quality of life of colostomy patients may be best taken care of by
      qualified stomatherapists, out-patient proctology departments and the ileo
      colostomy movement (ILCO).

PMID- 7566931
TI  - [Effect of preeclampsia on neonatal morbidity].
AB  - In this study the outcome of two groups of premature infants born by caesarean
      section were compared from 52 hypertensive mothers with severe pre-eclampsia and
      from 30 normotensive mothers. The indication of caesarean section in pre
      eclampsia was: proteinuria (> 500 mg/24 h), high blood pressure (> 160/100 mmHg),
      abnormal cardiotocogram and abnormality in flowmetry (fetal distress). Every
      infant was premature as well as in the control group. Significantly smaller mean
      birthweight and longer nursing-time in neonatal intensive care unit (NICU) were
      found in the pre-eclamptic group. Neonatal illnesses and complications are more
      frequent in the pre-eclamptic group. The time of ventilation was also longer.
      There are more early neurological disorders in the pre-eclamptic group than in
      the control one. The authors can establish that pre-eclamptic toxemia increases
      the morbidity in the neonatal period. This is due to the chronic intrauterine
      fetal distress as well as the retardation.

PMID- 7566932
TI  - [The role of laparoscopy in the management of prostatic cancer].
AB  - Laparoscopic lymphadenectomy is a new surgical modality with increasing usage in
      the staging and management of prostate carcinoma. Since the presence or absence
      of metastatic disease in the pelvic lymph nodes must be assessed for proper
      treatment planning, and preoperative staging studies have a high rate of false
      negative results, histological evaluation of the pelvic lymph nodes should be
      performed prior to radical prostatectomy. Laparoscopic pelvic lymphadenectomy is
      a well tolerated, safe, and accurate alternative to the conventional open
      surgical procedure.

PMID- 7566934
TI  - [OH-QUIZ: the incubation period of tetanus].

PMID- 7566933
TI  - [Vasoactive polypeptide-producing pancreatic carcinoma].
AB  - Authors report a case of Verner-Morrison syndrome which occurred in a 75-year-old
      man. The syndrome was caused by a pancreas VIP-oma with the histological
      structure of adenocarcinoma. Treatment with somatostatin analogous (octreotid)
      was effective, but the outcome was lethal due to subsequent pulmonary embolism.

PMID- 7566935
TI  - [The importance of the Hungarian Medical Index (HSZM)].

PMID- 7566937
TI  - [The scapula: rare localization of osteochondroma].
AB  - The authors demonstrate their 6 cases of scapular exostoses which were operated
      on between 1973 and 1993 at the Orthopaedic Department of the Medical University
      of Pecs. Results of the surgery with a mean five year follow up are discussed,
      and the literature data of incidence, diagnosis and treatment are reviewed. With
      resection of the osteochondroma good results were achieved in all of the cases.

PMID- 7566936
TI  - [Rheumatic fever, a disease undergoing change, based on the experience of the
      past 15 years].
AB  - The authors reviewed the records of paediatric patients treated at the cardiology
      department of the Svabhegyi Gyermekgyogyintezet during the period from 1 January
      1979 to 31 December 1993. All the patients elected for the survey had rheumatic
      fever and represented about 20 percent of the national patient pool. Among the 62
      children referred for suspected rheumatic fever 26 had carditis, and 3 suffered
      from pancarditis. Two children had chorea minor with carditis and there were 2
      additional cases with chorea minor only. Valvular heart disease has developed in
      21 patients. There were 16 patients with mitral regurgitation, these conditions
      have occurred in combination with mitral stenosis in 3 cases, whereas the
      insuffitientia of the aortic valve developed in two patients. The authors
      analysed the clinical signs of the patients and established that the chronic
      syndromes came in front. The authors have observed a favourable trend in the
      epidemiology of the disease, in particular, while 34 patients were referred
      during the first 5 years, there were only 18 cases in the second 5-years period.
      During the interval from 1989 to 1993, only 10 children with rheumatic fever have
      been referred to or treated at the authors' institute.

PMID- 7566938
TI  - [Treatment of chronic alcoholic pancreatitis with a new acid-resistant pancreatin
      product].
AB  - The authors summarised pathophysiology and therapy possibility of the chronic
      alcoholic pancreatitis. They introduce a new product of pancreatin use for
      treatment of chronic alcoholic pancreatitis. The aim of this prospective study
      was to asses the efficacy of this new drug in the treatment of chronic alcoholic
      pancreatitis. The treatment was carried out by new pancreatin product containing
      10,000 FIP U lipase, 9000 FIP U amylase, and 500 FIP E protease. During the study
      30 patients--suffering from alcoholic pancreatitis--were treated. They received,
      two tablets three times daily in a period of two weeks. The following parameters
      were observed and compared before and after the period of treatment: complaints
      of the patients, the characteristics of the stool (daily weight, frequency, fat
      contents, consistency) the change of the body weight and degree of abdominal
      pain. These parameters were compared using a score-system, before and after the
      period of treatment. The authors could analyse the data of 21 patients. It was
      proved that there was a significant decrease in frequency, daily weight and fat
      contents of the stool and in abdominal pain. There was not significant change in
      the body weight. The authors concluded that this new product is a good pancreatin
      preparation which is useful and suitable for effective treatment of chronic
      alcoholic pancreatitis, if the patient keeps abstinence.

PMID- 7566939
TI  - [Role of a mediator in the prevention of malpractice suits].
AB  - The authors suggest to inaugurate a new prevention proceeding suitable for the
      quick ending of the more and more often conducted litigated issues between
      patients and physicians (health care providers), by framing the mediator system.
      They outline the organisation, authority, and the personal conditions of being
      appointed to mediator. They emphasize the difference between the board of
      arbitration and the mediator system.

PMID- 7566941
TI  - [Remembering Camillo Reuter (1874-1954)].

PMID- 7566940
TI  - [Atypical course of Kawasaki syndrome in a 3-month old infant].
AB  - The authors report on the case history of a three-month-old infant with Kawasaki
      syndrome. The course of the disease was atypical, the various symptoms
      (antibiotic resistant high fever, urticariform rash, meningitis serosa, steril
      pyuria, coronaria aneurysma, thrombocytosis, high sedimentation rate) developed
      slowly during a period of several weeks. The authors intend to point out that
      Kawasaki-syndrome may appear in early infancy, frequently in an atypical way.

PMID- 7566943
TI  - [Surgical management of voice and speech disoreders in childhood. Phonosurgery].
AB  - By phonosurgery is meant the sum total of operative techniques that are aimed
      primarily or solely at the improvement of voice or speech. The different methods
      of phonosurgery can be used first of all for reducing or ceasing the pathological
      change of the voice quality, the dysphony and the rhinophony. The techniques
      recommended for the improvement in dysphony are: direct surgeries on the vocal
      cords (extirpation methods, intracordal injections) and indirect interventions
      affecting the cartilaginous frame of the larynx; some neurosurgical methods
      (nerve-to-nerve anastomosis) are curiosities and the larynx transplantation may
      show only the future trends. The surgical correction of the hyperrhinophony due
      to velopharyngeal insufficiency constitutes the other main group of phonosurgery.
      The velopharyngoplasty (flap surgery) is the most common technique among them.
      The author categorizes the surgical indications and methods (mostly concerning
      children) on the basis of his 38 years experience. Removal of vocal cord nodules
      was performed in 7% of 1740 children with dysphony. The importance of the complex
      treatment in these cases (speech therapy, medicines, psychotherapy) is stressed.
      Endolaryngeal interventions (implantation, cutting of a membrane or scars) may
      only be considered in children when voice problems exist alone without
      respiratory difficulties. The author has carried out 1000 velopharyngoplasties
      because of severe hypernasality with different etiology. Anatomical healing was
      good in 98% of the cases with no mortality; the hyperrhinophony disappeared in
      90% of the patients. The ideal age for operation is 4 1/2-5 years. Team work and
      a competent postoperative logopedic treatment are essential to obtain good
      results.

PMID- 7566942
TI  - [Bath Pages--in the service of balneology].

PMID- 7566944
TI  - [Management of pancreatic necrosis].
AB  - The authors report on the results of operations successively carried out in the
      last one and a half years on 10 patients with pancreatic and peripancreatic
      necrosis. On admission objective prognostic signs were quantified according to
      Ranson (average: 4.89), and the prognoses of serious disease-processes were
      correctly determined. On admission on the intensive care unit APACHE II points
      were calculated (average: 13.9), and the individual risk of hospital mortality
      (average: 42.2%) was defined. In spite of this high average, only 2 patients were
      lost (20% actual mortality). This can be attributed to monitoring the patients in
      the intensive care unit, successful therapy of multiorgan dysfunctions and
      failures, radical necrectomy, continuous lavage of the lesser sac, epidural
      sympathicolysis, reoperations performed in time, total parenteral and jejunal
      nutrition, and antibiotic therapy based on results of serial cultures. The
      authors point to the possibility of infection originating sometimes from the
      treatment applied, mostly from repeated operations. For the sake of improvement
      and international comparison of the results they suggest the application of
      Ranson- and APACHE II scores in medical, surgical and intensive care units, where
      the treatment of patients with acute pancreatitis takes place. The subsequent
      complete restitution of the saved patients justifies the long-lasting and
      expensive treatment.

PMID- 7566945
TI  - [The effect of prolonged acenocoumarol therapy on bone density].
AB  - The effect of chronic cumarin treatment on bone mineral content was investigated.
      Bone mineral density was determined by double photon densitometry (Lunar DPXL).
      The density data (mean +/- SE) of 45 cardiac patients (age: 57.0 = +/- 6.3 y,
      body mass index: 26.7 +/- 3.8 kp/m2, cardiac stadium score, according to New York
      Heart Association: 2-3), had been treated by acenocumarol at least for 2 years
      (duration of treatment: 75.0 +/- 52 months), were compared to the values of 45
      age, body mass index, cardiac status matched patients not treated by
      anticoagulant. The density values of L2-L4 lumbar regions were lower in the
      treated group (1.041 +/- 0.17 vs. controlls: 1.13 +/- 0.15 g/cm2, p < 0.05),
      while no differences in ultradistal ulnar and radial regions were detected. No
      correlation between bone mineral density and the length, or the dose of the
      cumarin treatment were observed. This observation suggests the importance of the
      regular bone densitometry control of cumarin treated patient.

PMID- 7566946
TI  - [Paternity determination using the RFLP method in DNA probes].
AB  - By the discovery of restriction fragment length polymorphism and hypervariable
      minisatellite sequences paternity testings have become possible with almost one
      hundred percent probability. The procedure is based on the improvement of DNA
      probes which can recognize the different regions of minisatellites in the whole
      site of human genome. These sequences are found in noncoding regions of DNA, in
      the so-called intrones, in areas between genes. The sequence motives have a
      discriminating power and provide a possibility to distinguish individuals.

PMID- 7566947
TI  - [Amidazophen. Yes or no?].
AB  - The authors compare the side effects and hazards of the use of Paracetamol and
      Amidazophen on the basis of literary data. They draw the conclusion that in case
      of illnesses accompanied by fever, Amidazophen is preferable as an antifebrile,
      on both professional and cost-effectiveness grounds. This conclusion is supported
      by an acute tubularis necrosis case, where a direct link is suspected between the
      use of Paracetamol as an antifebrile and the development of kidney damage.

PMID- 7566948
TI  - [Anti-adhesive and anti-thrombotic effects of integrin-inhibiting tripeptides
      (Arg-Gly-Asp)].
AB  - The RGD (Arg-Gly-Asp) motif has a widespread distribution in the cellular
      adhesive structures on platelets, lymphocytes, some viruses and matrix proteins.
      RGD sequence seems to confer adhesive properties to macromolecular proteins like
      fibronectin, vitronectin, von Willebrand factor, fibrinogen and many others. So
      RGD tripeptide and its analogues really deserve to be regarded as general
      disintegrin sequence. A concise review is given to analyze the most important
      achievements by using RGD peptides as antiplatelet agents along with an overview
      of the potential clinical application of the disintegrin peptides in other fields
      of medicine.

PMID- 7566949
TI  - [Experience with microbiological studies of the diabetic foot].
AB  - In order to determine the microbiological characteristics of diabetic foot
      infection, 60 diabetic patients (21 women, 39 men; age between 43 and 89 years
      with a duration of diabetes from 0.5 to 37 years) were investigated. Immediately
      after the hospitalisation specimens from infected foot lesions were taken using
      Port-A-Cul special transport medium. Aerobic cultures were done in all cases
      according to conventional methods while anaerobic cultures were carried out when
      clinical signs indicated to perform it. Out of 60 lesions only 2 proved to be
      sterile. In the remaining 58 patients a total of 138 isolates were found
      resulting in an average of 2.3 organisms per lesions. Only aerobic isolates were
      identified in 45 patients whereas anaerobic species were also found in 12
      patients. Only Candida was found in 1 patient while Candida in combination with
      bacterial strains was observed in 3 patients. In antimicrobial susceptibility
      testing beta-lactamase-stable antibiotics with broad spectrum, covering
      enterococcus and anaerobic organisms proved to be most effective. Diabetic foot
      infections have a polymicrobial nature. Antibiotic treatment of infections should
      be based on the results of microbiological investigation of diabetic foot.

PMID- 7566950
TI  - [Management of Oddi sphincter dyskinesis. Results of drug therapy and
      sphincterotomy].
AB  - In a retrospective evaluation, the outcome of the long term treatment of the
      sphincter of Oddi dyskinesia (OD, type III. dysfunction) has been analysed.
      PATIENTS AND METHOD: Therapeutic results of 64 cholecystectomised patients with
      OD were evaluated by means of regular follow-up and questionnaire filled in
      either by the patients or their practitioners. RESULTS: Conservative treatment
      (nitroglycerin, calcium channel blocker or both) resulted in symptom-free
      condition or improvement with 53% of the patients (37/64). Out of 27 patients
      whose condition did not improve by combined drug therapy, in 20 cases endoscopic
      sphincterotomy (EST) and in 1 case transduodenal sphincterotomy were performed.
      Having followed sphincterotomy, out of 21 patients only 9 became symptom-free and
      5 improved. CONCLUSIONS: Therapeutic benefit of sphincter relaxants fail in
      nearly half of the cases with OD, and even sphincterotomy can lead to symptomless
      condition only in a portion of OD. Regarding the high incidence of complications
      following EST in OD, it can only be recommended after failure of the conservative
      therapy in correctly diagnosed cases. The results emphasise a need for a
      prospective randomised controlled clinical study to seek for the optimal
      therapeutic regimen.

PMID- 7566951
TI  - [Successful treatment of cyclic neutropenia associated with hyperimmunoglobulin M
      syndrome using recombinant granulocyte-colony stimulating factor].
AB  - Hyper-IgM syndrome associating with severe neutropenie presenting in irregularis
      cycles was diagnosed in a 3-year-old male patient. His elder brother died of
      sepsis which appeared as a consequence of dysgammaglobulinaemia and neutropenia
      at the age of 9. We could not achieve a parmanent good result with the monthly
      immunoglobulin substitution and supportive treatment. The candida infection of
      the gingiva and of the oral mucous membrane expanded to the esophagus resulting
      in its complete occlusion and temporarily a gastrostomy was needed to feed him.
      We started with the recombinant human granulocyta colony stimulating factor (rh-G
      CSF) treatment at the age of 6. We tried several ways of applying and finally the
      10 micrograms/kg/dose given subcutan, for 5-10 days from the nadir of the
      neutropenic cycle seemed the most effective. The rh-G-CSF treatment resulted in
      an increase of ANC and the complete resolution of gingivostomatitis. The
      incidents of infections, the requirement of antibiotics and the duration of
      hospitalisation were markedly reduced. The consequent improvement in his physical
      condition made it possible to finally resolve the esophageal stricture
      surgically. We have not observed any neutropenic cycle since the end of the 14
      month rh-G-CSF treatment. Though the medicine was discontinued there has been no
      recidiva for more than 22 months.

PMID- 7566952
TI  - [Acute renal failure in neuroleptic malignant syndrome].
AB  - The neuroleptic malignant syndrome is characterized by hyperpyrexia, muscle
      rigidity, extrapyramidal motion disorder, vegetative symptoms and mental
      disorientation. This group of symptoms develops abruptly and may lead to serious
      complications. One of these complications is the acute renal failure. Permanent
      muscle rigidity causes the damage of muscle cells which result in myoglobinaemia,
      myoglobinuria and elevations in muscle related creatine phosphokinase. The
      authors report the case of a young man who underwent neuroleptic medication
      because of hebephrenia. During the medication the following symptoms were
      developed: extrapyramidal symptoms, restlessness, muscle rigidity, high fever.
      These symptoms eventually lead to acute renal failure caused by rhabdomyolysis
      (characteristic urine finding, significant elevations in serum creatine
      phosphokinase). With regards to the neuroleptic malignant syndrome dantrolenum
      and bromocriptin treatment were applied with the discontinuation of neuroleptic
      medication. As a part of the complex therapy a massive volumen-supplementing and
      alkalizing treatment was used but haemodialysis had also become necessary. During
      the above mentioned treatment symptoms referring to the neuroleptic malignant
      syndrome resolved and the acute renal failure was cured. The case report calls
      attention to a specific group of symptoms and the possibilities for prevention
      and treatment. The above case report is the first observation in Hungary.

PMID- 7566953
TI  - [Medical history in the journal Orvosi Hetilap].

PMID- 7566955
TI  - [Transfer of activities of daily living to the operating room].

PMID- 7566954
TI  - [Remembering Wilhelm Conrad Rontgen on the centenary of his discovery and the
      150th anniversary of his birth].

PMID- 7566956
TI  - [Planning of care in the operating room].

PMID- 7566957
TI  - [Outpatient pediatric surgery at the Vienna General Hospital].

PMID- 7566958
TI  - Wild type p53 and c-myc co-operation in generating apoptosis of a rat
      hepatocellular carcinoma cell line (FAA-HTC1).
AB  - p53 and c-myc are both known to be involved in apoptotic cell death as well as
      positive or negative regulation of cell proliferation, but it is not well
      established whether their functions are mechanistically correlated. We found that
      FAA-HTC1 cells, a rat hepatocellular carcinoma cell line, expressed c-myc
      independently of cell cycle and no detectable p53. To investigate possible co
      operation between p53 and c-myc, the dexamethasone (Dex)-inducible wild type rat
      p53 was stably transfected into this cell line and c-myc expression was
      suppressed by treatment with c-myc antisense oligonucleotide (AS). p53 expression
      in the p53-introduced derivative resulted in apoptotic cell death, but it did not
      inhibit proliferative growth of the viable cells. On the other hand, when c-myc
      was suppressed in the p53-expressing cells, both apoptosis and cell growth were
      inhibited. These results indicate that p53 can act in the same cells either as a
      growth-inhibitor or apoptosis-inducer depending on the status of c-myc
      expression.

PMID- 7566959
TI  - Bicistronic retroviral vector reveals capacity of v-erbA to induce
      erythroleukemia and to co-operate with v-myb.
AB  - Previous studies have shown that v-erbA and v-myb can induce the proliferation of
      avian erythroid cells in culture. To study the combined effects of v-erbA and v
      myb, the two oncogenes were engineered into a retrovirus bicistronic vector with
      an internal ribosomal entry site (IRES) or into a vector with a splice acceptor
      (SPL). This allowed coexpression of the two proteins and a comparison with the
      same vector containing either v-erbA or v-myb only. Both the erbA IRES and the
      erbA/myb IRES virus constructs transformed erythroid cells after infection of
      bone marrow or blastoderm cultures. The erbA/myb IRES virus exhibited a 5-10-fold
      higher transformed colony forming efficiency than the erbA IRES virus in the
      blastoderm assay. Surprisingly, when injected into chicken embryos in the
      presence of helper virus, both viruses induced an erythroleukemia in about half
      of the animals. In contrast, no leukemia was observed with a myb IRES virus, with
      spliced vectors containing v-erbA alone or v-erbA in combination with v-myb, nor
      with erbA IRES and erbA/myb IRES viruses produced in the absence of helper virus.
      The average latency of leukemia induction was shorter for the erbA/myb IRES virus
      (3.5 weeks) than for the erbA IRES virus (5 weeks). Nevertheless, for both
      viruses the leukemic blasts retained full factor dependence for growth. These
      results show that v-erbA is capable of inducing an erythroleukemia when expressed
      by a high titer bicistronic retrovirus under conditions of virus spreading and
      that its in vitro and in vivo transforming potential can be enhanced by v-myb.

PMID- 7566960
TI  - The EBV-encoded LMP1 protein inhibits p53-triggered apoptosis but not growth
      arrest.
AB  - We have previously shown that exogenous wild type p53 induces apoptosis in the
      Burkitt lymphoma line BL41 that carries endogenous mutant p53, using a
      temperature sensitive p53 construct expressed as mutant p53 at 37 degrees C and
      wild type p53 at 32 degrees C (Ramqvist et al., Oncogene, 8, 1495-1500, 1993). We
      also found that wild type p53-induced apoptosis is blocked by bcl-2 in a mouse T
      lymphoma line (Wang et al., Oncogene, 8, 3427-3431, 1993) The Epstein-Barr virus
      (EBV)-encoded latent membrane protein 1 (LMP1) can protect Burkitt lymphoma cells
      from apoptosis induced by low serum. In order to test if LMP1 can block p53
      triggered apoptosis, we infected BL41 cells expressing the ts p53 construct with
      an LMP1-carrying retrovirus. The LMP1-expressing BL41-ts p53 cells were arrested
      in G1 upon induction of wild type p53 expression at 32 degrees C, but did not
      enter apoptosis as shown by the absence of positive TUNEL staining. WAF1/p21 mRNA
      was induced at 32 degrees C in both the ts p53-expressing and ts p53/LMP1
      expressing BL41 cells. Thus, LMP1 prevents p53-induced apoptosis but does not
      interfere with induction of WAF1/p21. The LMP1-infected cells expressed elevated
      bcl-2 protein levels. Therefore, our data suggest that LMP1 blocks p53-triggered
      apoptosis but not G1 arrest by upregulating bcl-2 expression.

PMID- 7566961
TI  - Requirement of the ETS domain transcription factor D-ELG for egg chamber
      patterning and development during Drosophila oogenesis.
AB  - The D-elg gene encodes an ETS domain transcription factor that functions in
      Drosophila oogenesis. D-elg belongs to a small group of genes that are required
      for the formation of both the anteroposterior and dorsoventral axes of the egg
      chamber. During oogenesis in D-elg mutant females, the spatial localization of
      oskar and gurken mRNAs in the oocyte is disrupted and a follicle cell enhancer
      trap marker identifies dorsoventral polarity defects. Also, specialized follicle
      cells, called border cells, fail to migrate from their anterior location to a
      position adjacent to the developing oocyte. Consistent with these phenotypes, D
      elg shows genetic interactions with two genes required for normal egg chamber
      differentiation.

PMID- 7566962
TI  - Alternative splicing of PSP94 (prostatic secretory protein of 94 amino acids)
      mRNA in prostate tissue.
AB  - While performing reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis of total mRNA from prostate cancer specimens, two forms of PSP94 cDNA
      were detected. RT-PCR products were analysed by Southern blotting and probing
      with exon-specific oligonucleotides. In the short form of PSP94 mRNA, designated
      as PSP57, exon III was found to be deleted. The two mRNA forms were confirmed by
      cloning and sequencing of the RT-PCR products and were found to result from
      alternative splicing. The alternatively spliced form, PSP57, was characterized by
      sequence analysis. PSP94 and PSP57 possess identical exons I and II, including
      identical secretion signal peptide and the 5' untranslated sequences. PSP57 has a
      frame-shifted exon IV and encodes a putative 57 amino acid protein with a novel,
      highly basic C-terminus of 41 amino acids. PSP57 mRNA was detected in other
      urogenital tissues (kidney, bladder) and in most tumor cell lines tested, but was
      not detectable in other tissues such as breast and lung. In prostate tumor cell
      lines, PSP57 mRNA was aberrantly spliced and localized in the nuclear fraction of
      the cell. Our results suggest the possible existence of a novel PSP protein that
      originates from alternative splicing of PSP94 mRNA in urogenital tissues.

PMID- 7566963
TI  - Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS
      fusion transcripts.
AB  - Cytogenetic analysis of Ewing's sarcoma, primitive neuroectodermal tumors and
      Askin tumors revealed characteristic translocations t(11;22) or t(21;22).
      Molecular analysis of these translocations revealed 5'-region of EWS gene (from
      band 22q12) is fused to the 3'-region of either Fli-1 gene (from band 11q24) or
      erg gene (from band 21q22). Functional characterization of the EWS-Fli-1 and EWS
      erg chimeric proteins suggested that they function as transcriptional activators.
      In order to develop therapeutic agents, it is essential to know whether
      expression of the EWS-fusion gene products is coupled to tumorigenicity of
      Ewing's sarcoma cells and if targeting the EWS-fusion products results in loss of
      tumorigenicity of Ewing's sarcoma cells. For this reason, we have made stable
      Ewing's sarcomas expressing antisense EWS-Fli-1 or EWS-erg expression plasmids.
      Expression of antisense EWS fusion transcripts resulted in a significant loss of
      endogenous EWS-Fli-1 and EWS-erg proteins in Ewing's sarcoma cells. These cells
      expressing antisense EWS fusion transcripts showed loss of anchorage independent
      growth and tumorigenicity in nude mice unlike the parental Ewing's sarcoma cells.
      These results demonstrate the necessity of a certain threshold level of
      expression of EWS-fusion products in the clonogenicity and tumorigenicity of
      Ewing's sarcoma cells and therefore emphasizes the importance of targeting the
      EWS-fusion products as a therapy for Ewing family of tumors.

PMID- 7566964
TI  - Cloning, chromosomal localization and expression analysis of the mouse Akt2
      oncogene.
AB  - We isolated mouse cDNA clones containing the entire coding region of the putative
      oncogene Akt2. Sequence analysis revealed that, like its human homolog, Akt2
      encodes a protein-serine/threonine kinase containing a pleckstrin homology domain
      at its amino terminus. Fluorescence in situ hybridization of the mouse cDNA to
      rodent metaphase spreads demonstrated that the Akt2 gene maps to mouse chromosome
      band 7B1 and rat chromosome 1q22. Expression levels of mouse Akt2 mRNA and Akt2
      protein varied among tissues, with the highest levels in skeletal muscle. Akt2
      expression was low in a multipotent fibroblast cell line, but it was upregulated
      when these cells were transformed with Myod and induced to differentiate into
      myocytes. These data demonstrate that Akt2 expression is activated during
      cellular differentiation and suggest that it functions in the signaling pathways
      of some adult tissues.

PMID- 7566965
TI  - Fas-dependent apoptosis is impaired by SV40 T-antigen in transgenic liver.
AB  - A transgenic mouse model for hepatocarcinoma has been previously produced by
      targeting SV40 T-antigen expression to the liver. To evaluate the perturbation of
      cell death occurring during hepatocarcinogenesis, we examined the Fas-induced
      apoptosis on hepatocytes expressing T-antigen. Whereas anti-Fas antibody induced
      apoptosis in primary cultured normal hepatocytes, they imparted a weak
      cytotoxicity on primary cultured hepatocytes expressing T-antigen. This
      resistance of hepatic Fas-mediated apoptosis appears to result in an enhancement
      of a protective mechanism involving the protein kinase C signaling pathway rather
      than in a down-regulation of Fas-antigen expression. We further demonstrated that
      anti-Fas antibody does not have as efficient a lethal effect in T-antigen
      transgenic mice as in wild-type mice. The livers of transgenic mice injected with
      anti-Fas mAbs showed large intact regions with a few scattered apoptotic bodies:
      these regions strictly corresponded with carcinoma nodules, expressing high level
      of T-antigen. Our results describe a novel function for SV40 T-antigen which
      could contribute to viral pathogenesis by protecting infected cells against the
      host apoptotic defense mechanism.

PMID- 7566966
TI  - Cyclic AMP stimulates a JunD/Fra-2 AP-1 complex and inhibits the proliferation of
      interleukin-6-dependent cell lines.
AB  - Interleukin-6 (IL-6) is a proinflammatory cytokine which also acts as a growth
      factor for some murine hybridomas (7TD1) or human myelomas (U266). We demonstrate
      that elevation of cAMP cellular content inhibits IL-6-stimulated cell growth, by
      blocking cells mainly in G1 phase. This inhibition is associated with increased
      expression of the Fos family protein Fra-2. Treatment of cells with 8Br-cAMP
      results in increased DNA-binding activity of two distinct AP-1 complexes;
      JunD/Fra-2 and JunB/Fra-2, and also in elevated AP-1 transactivation. When 8Br
      cAMP is withdrawn from the medium, cells enter S phase and Fra-2 protein levels
      and AP-1 DNA-binding activity decrease to their basal value indicating that a
      temporally correlation exists between the 8Br-cAMP-mediated induction of JunD/Fra
      2 AP-1 complex and the 7TD1 and U266 cell growth inhibition.

PMID- 7566967
TI  - Vav and Ras induce fibroblast transformation by overlapping signaling pathways
      which require c-Myc function.
AB  - Recent evidence has suggested that the Vav oncoprotein may function as a
      hematopoietic-specific GTP exchange factor for the Ras superfamily of proteins.
      However, transformation of NIH3T3 fibroblast cells by Vav is morphologically
      distinct from that induced by activated Ras oncogenes, suggesting that the two
      oncoproteins induce separate signal transduction pathways which promote
      transformation. To address this issue, the effects of dominant negative mutants
      of H-ras and proto-Vav (proto-VavR695L, a mutation in the VavSH2 domain) were
      tested on Vav- and Ras-induced transformation. These mutants partially inhibited
      both Vav- and Ras-induced transformation, suggesting that they may induce a
      common downstream signaling pathway which potentiates transformation. As an
      independent measure of Vav function we also tested the ability of the purified
      protein encoded by VavSH2 to influence Germinal Vesicle Breakdown (GVBD) during
      Xenopus oocyte maturation. Microinjection of the VavSH2 protein alone, but not
      mutant VavR695L SH2 protein, was sufficient to induce GVBD and accelerated
      maturation induced by normal Ras, suggesting that in this system as well Vav and
      Ras signals overlap through a common effector. A key target of multiple
      signalling pathways is c-Myc. Dominant negative versions of c-Myc totally
      abolished morphologic transformation of NIH3T3 cells by both Vav and Ras
      oncogenes. These results suggest that distinct, but overlapping, signalling
      pathways are induced by Vav and Ras and that fibroblast cell transformation by
      either oncogene requires c-Myc functions.

PMID- 7566968
TI  - Somatic mutations in the VI transmembrane segment of the thyrotropin receptor
      constitutively activate cAMP signalling in thyroid hyperfunctioning adenomas.
AB  - We have discovered two somatic mutations in the VI transmembrane domain of the
      thyrotropin receptor gene in thyroid hyperfunctioning adenomas. The mutated amino
      acid residues are phenylalanine 631 (to cysteine) and threonine 632 (to
      isoleucine). Cloning and expression of the mutated versions of the receptor in
      COS cells increased significantly the basal and the TSH-induced cAMP levels
      compared to the wild type receptor. Moreover, the expression of a reporter gene
      under the control of the cAMP-inducible promoter, was likewise constitutively
      activated in cells expressing the 631 and 632 TSH receptor mutants relative to
      the wild type. These data indicate that the VI transmembrane segment in the TSH
      receptor and presumably in the other G-protein coupled receptors is a critical
      domain for the activation of G-protein signalling and that the mutations
      described here may be the cause of the thyroid hyperfunctioning adenoma.

PMID- 7566969
TI  - Lymphoid- and myeloid-specific activity of the PU.1 promoter is determined by the
      combinatorial action of octamer and ets transcription factors.
AB  - The putative oncogene PU.1/Spi-1 is a member of the ets-family of transcription
      factors normally expressed in a subset of hematopoietic cell types. Here we have
      characterized the role of the PU.1 promoter region for the cell-type specific
      expression. The proximal 120 bp are sufficient to mediate a high level of
      activity specifically in B cells and macrophages. Three important motifs could be
      identified within this region. Two of them, an ets binding site (EBS) and a
      variant octamer motif were most important for cell-type-specific promoter
      activity in B cells and macrophages. An additional Sp1 motif stimulates basal
      activity of this promoter element. The relative contribution to overall activity
      of octamer motif and EBS differs in B cells and macrophages. In B cells, both
      octamer motif and EBS combine to mediate high level activity, whereas in
      macrophages the EBS predominantly confers promoter activity. Both the Oct1 and
      Oct2 transcription factors, presumably in combination with a B-cell-restricted
      coactivator, are responsible for the activity of the variant octamer motif in B
      cells. Interestingly, the PU.1 transcription factor can functionally interact
      with the EBS in its own promoter, suggesting a positive feedback regulation.

PMID- 7566971
TI  - Hematopoietic transforming potential of activated ras in chimeric mice.
AB  - Although activating mutations in ras genes are the most common genetic
      abnormality in human hematologic malignancies, the role of ras mutations as an
      initiating event in leukemogenesis remains unclear. To assess the consequences of
      ectopic expression of an activated ras gene in normal hematopoietic cells in
      vivo, lethally irradiated mice were reconstituted with bone marrow cells infected
      with a mutant ras-containing retrovirus [murine stem cell virus (MSCV)-v-H-ras]
      based on the MSCV retroviral vector which efficiently transduces functional genes
      into hematopoietic stem/progenitor cells. Despite a marked myeloid leukocytosis
      detectable in the peripheral blood within 4 weeks of engraftment, none of 22
      primary or secondary transplant recipients studied for longer periods of time
      presented with myeloid neoplasms. Instead, 18 of the MSCV-v-H-ras mice developed
      pre-T-cell thymic lymphomas and/or pre-B-cell lymphoblastic leukemia/lymphomas
      between 7 and 12 weeks post-transplantation. The pre-B and pre-T lymphoid tumors
      that arose in one animal were shown to harbor a common MSCV-v-H-ras provirus,
      indicating that the target cell for transformation was a bipotential lymphoid
      precursor. To more precisely examine the effects of activated ras expression on
      the behavior of hematopoietic progenitors, infected bone marrow cells were
      assayed in methylcellulose cultures under conditions favorable for growth of
      multilineage myeloid colonies or were passaged as bulk suspension cultures in the
      presence of various hematopoietic growth factors, including interleukin (IL)-3,
      IL-4, IL-6 and IL-7. MSCV-directed expression of v-H-ras selectively promoted the
      formation of large dense colonies comprised of monocyte-macrophages in
      methylcellulose cultures. When transferred to liquid cultures, the vast majority
      of the cells underwent terminal macrophage differentiation. By comparison,
      tumorigenic B-lymphoid and mixed lymphoid/myeloid cell lines were routinely
      established from the bulk suspension cultures, with cell lines of predominantly
      myeloid phenotype emerging only in IL-6-supplemented cultures. These results,
      considered together with previous findings, suggest that activating ras mutations
      could be an initiating genetic alteration in human acute lymphoblastic leukemia
      but are more likely to be a post-initiation change in human acute myeloid
      leukemia.

PMID- 7566970
TI  - Quantitative analysis of Grb2-Sos1 interaction: the N-terminal SH3 domain of Grb2
      mediates affinity.
AB  - Grb2 is an adaptor protein that links receptor and cytoplasmic tyrosine kinases
      to the Ras signalling pathway by binding the Ras-specific guanine nucleotide
      exchange factor, Sos1, through its SH3 domains. The Grb2-SH3 domain binding has
      been localized to the carboxy-terminal two hundred amino acids of Sos1 (Sos1-c).
      By using real time biospecific interaction analysis (BIAcore), we studied the
      kinetic parameters and binding affinity of the Grb2-Sos1-c interaction. The
      binding of Grb2 to Sos1-c is a high affinity interaction with a moderate
      association rate (9.45 x 10(4) per M per s), a slow dissociation rate (13.8 x 10(
      5) s), and an affinity constant of 1.48 nM. BIAcore measurements on isolated N
      terminal and C-terminal SH3 domains (NSH3 and CSH3) further indicate that the
      high affinity Grb2-Sos1-c interaction is primarily mediated through the NSH3
      domain (Kd = 1.68 nM). The CSH3 domain shows substantially reduced binding to
      Sos1-c in these measurements. Inhibition studies with BIAcore using proline rich
      peptides derived from the C-terminus of Sos1 show that there is a single major
      binding site for Grb2 in Sos1. This binding site is contained within the peptide
      N20, which corresponds to amino acids 1143-1162 of Sos1. This peptide completely
      blocks the Grb2-Sos1-c and NSH3-Sos1-c interactions with IC50 values of 8 microM
      and 4 microM respectively. The discrete interaction between the NSH3 domain and
      the N20 peptide may be amenable for drug discovery through screening or
      peptidomimetic approaches.

PMID- 7566972
TI  - Increase in expression levels of interferon-inducible genes in senescent human
      diploid fibroblasts and in SV40-transformed human fibroblasts with extended
      lifespan.
AB  - The normal human fibroblast line, TIG-3 which senesces at around 80 population
      doubling levels (PDLs), expressed interferon (IFN)-inducible genes such as 6-16,
      2', 5'-oligoadenylate synthetase (2,5-A) and HLA B7 near the end of the
      proliferative lifespan. Other normal fibroblast line such as MRC-5 also expressed
      IFN-inducible genes when senesced. Clones transformed with SV40 T-antigen, which
      extended their proliferative lifespan by about 20-30 PDLs, also expressed IFN
      inducible genes during their extended life. Anti-IFN-beta antibodies added in
      culture medium repressed the expression of IFN-inducible gene in both normal
      senescent and life-extended SV40-transformed cells. IFN-beta repressed DNA
      synthesis in normal TIG-3 and induced IFN-inducible genes in both normal and SV40
      transformed TIG-3. Conditioned medium recovered from life-extended SV40
      transformed cells contained IFN-beta, but not IFN-alpha, IFN-gamma or TNF-alpha
      and possessed an activity that inhibited DNA synthesis of young TIG-3. Addition
      of anti-IFN-beta antibodies into the medium enhanced the serum-induced DNA
      synthesis of near senescent (91% lifespan completed) TIG-3, while it neither
      induced DNA synthesis in fully senescent TIG-3 nor extended the proliferative
      lifespan of TIG-3. These results suggest that normal and SV40-transformed human
      fibroblasts increase expression of IFN-beta with increasing proliferative age
      especially near the end of their lifespan resulting in induction of IFN-inducible
      genes and possibly in growth repression.

PMID- 7566973
TI  - Two distinct FUS breakpoint clusters in myxoid liposarcoma and acute myeloid
      leukemia with the translocations t(12;16) and t(16;21).
AB  - The FUS gene, which maps to 16p11, is fused to the CHOP gene in the t(12;16)
      (q13;p11) that characterizes myxoid liposarcomas (MLS) and to the ERG gene in
      acute myeloid leukemia (AML) with t(16;21) (p11;q22). In the present study we
      have mapped the breakpoints within FUS in 13 MLS with t(12;16) and in one AML
      with t(16;21). This region of FUS is about 3.9 kb and contains four exons. The
      breakpoints clustered to two zones (1 and 2). A strong association was found
      between the two known types of FUS/CHOP transcripts and the genomic localization
      of the breakpoints. In all cases expressing only type I or both type I and II
      FUS/CHOP transcript the genomic breakpoints mapped to zone 1. In all cases
      expressing only the type II transcript the breakpoints occurred in zone 2. The
      breakpoint in the AML case was in zone 1, suggesting that in-frame fusion
      transcripts are selected by similar mechanisms in both MLS and AML.

PMID- 7566974
TI  - Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and
      the yeast cell cycle regulators BUB2 and cdc16.
AB  - In an effort to identify genes that are differentially regulated during mast cell
      development, subtracted cDNA prepared from wild-type murine P815 mastocytoma
      cells and a P815 subline that exhibits properties of mast cell differentiation
      was used to screen mast cell cDNA libraries. Several known mast cell-specific
      cDNAs were isolated including mast cell carboxypeptidase A (MC-CPA), murine mast
      cell protease-5 (MMCP-5), and gp49. A novel cDNA, designated Tbc1, was identified
      that showed differential expression in the two mast cell lines. The amino acid
      sequence predicted from the cDNA contains a 200 amino acid domain that is
      homologous to regions in the tre-2 oncogene and the yeast regulators of mitosis,
      BUB2 and cdc16. The N-terminal region contains a number of cysteine and histidine
      residues, potentially encoding a zinc finger domain. Tbc1 is a nuclear protein
      and is expressed in highest levels in hematopoietic cells, testis and kidney.
      Within these tissues, expression of Tbc1 is cell- and stage-specific. Based on
      sequence similarity, pattern of expression and subcellular localization, Tbc1 may
      play a role in the cell cycle and differentiation of various tissues.

PMID- 7566975
TI  - Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell
      lines expressing p210BCR/ABL.
AB  - The BCR/ABL oncogene causes chronic myelogenous leukemia (CML) in humans and
      induces growth factor independence of hematopoietic cell lines in tissue culture.
      p210BCR/ABL is localized at least in part to the cytoskeleton, and has been shown
      to interact directly with actin filaments through an actin binding domain located
      in the C-terminus of ABL. CML cells have reduced adhesion to some extracellular
      matrix components but the mechanism of this phenomenon is unknown. In this study
      we examined tyrosine phosphorylation of focal adhesion proteins in cells
      expressing p210BCR/ABL. An interleukin-3 (IL-3)-dependent cell line, 32Dc13, was
      transformed with a BCR/ABL cDNA, and the patterns of localization, expression,
      and tyrosine phosphorylation of focal adhesion proteins were compared among
      untransformed 32Dc13 cells with and without IL-3 stimulation and BCR/ABL
      transformed 32Dc13 cells. Of the focal adhesion proteins examined, only paxillin
      exhibited tyrosine phosphorylation in response to IL-3; while in cells
      transformed by p210BCR/ABL, paxillin, vinculin, p125FAK, talin and tensin were
      constitutively tyrosine phosphorylated. IL-3 induced a transient association
      between paxillin and vinculin, while in BCR/ABL-transformed cells, several
      proteins coimmunoprecipitated with paxillin, including vinculin, p125FAK, talin
      and tensin. Pseudopodia enriched in focal adhesion proteins were transiently
      detected in 32Dc13 cells in response to IL-3, but constitutively detected in
      cells expressing p210BCR/ABL. p210BCR/ABL protein was also found concentrated in
      punctate structures adjacent to the cell membrane in myeloid cell lines, which
      often contained vinculin and paxillin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7566976
TI  - Resistance to Fas-mediated apoptosis in human hepatoma cells.
AB  - CTLs- and lymphokine-induced apoptosis of infected hepatocytes during the course
      of chronic viral hepatitis is thought to be important for both disease
      termination and prevention of hepatocellular transformation. We therefore studied
      apoptosis induced by Fas (APO-1 or CD95)-a widely expressed cell surface receptor
      whose ligand is involved in lymphocyte cytotoxicity-in a set of human hepatoma
      cell lines. As normal hepatocytes, all of the human hepatoma cell lines tested do
      express detectable amounts of Fas on their surface. Nevertheless, only PLC/PRF/5
      cells undergo apoptosis following treatment with anti-Fas. Systematic cloning and
      sequence analysis of the Fas cDNA did not show mutations in the Fas gene in any
      of the cells lines tested. However, due to alternative splicing, 5 to 10% of the
      Fas cDNAs are deleted of 63 internal nucleotides corresponding to the
      transmembrane domain, thus encoding for a soluble and secreted form of Fas (Fas
      delta TM), potentially able to neutralize anti-Fas or Fas-Ligand. Although we
      could not demonstrate a direct correlation between resistance of different
      hepatoma cell lines to Fas mediated death and endogenous expression of this
      transcript, we show that PLC/PRF 5 stable transfectants overexpressing Fas delta
      TM are less sensitive to anti-Fas than control cells. In three different cell
      lines, resistance to anti-Fas was overcome by treatment with the protein
      synthesis inhibitor cycloheximide. Although this could suggest the existence of
      short-lived repressors of the Fas-activated apoptotic signalling pathway(s), we
      show that translational inhibition is not required for the synergistic effect of
      cycloheximide to take place, and that resistant hepatoma cells can be sensitized
      to anti-Fas by subinhibitory concentrations of this protein synthesis inhibitor.
      Since cycloheximide is able to activate intracellular signalling independently on
      its effects on protein synthesis, we suggest that it might provide a
      costimulatory signal that cooperates with Fas in the induction of cell death and
      that, at least in the cells we tested, resistance to Fas is not an active process
      involving gene transcription and translation but only the consequence of an
      inadequate apoptotic stimulation.

PMID- 7566977
TI  - Structural analysis of human and murine flt3 ligand genomic loci.
AB  - Both the murine and human genomic loci that encode flt3 ligand have been cloned.
      flt3 ligand is a hematopoietic growth factor that stimulates the proliferation of
      stem and progenitor cells. The portions of the murine and human flt3 ligand
      genomic loci encompassing the coding region of the protein are approximately 4.0
      kb and 5.9 kb, respectively. The human genomic locus is larger as a result of the
      presence of repeated sequences within introns I, II, IV, V and VI. The
      transmembrane isoform of the murine and human flt3 ligand proteins are each
      encoded within seven exons (1-5 + 7 and 8). Analyses of flt3 ligand cDNA clones
      show that alternative splicing of a putative sixth exon results in the generation
      of a soluble form of the flt3 ligand protein. The sizes of each of the exons are
      well conserved between species. Murine and human flt3 genomic loci have a similar
      exon: intron structure compared to the genomic loci encoding Steel factor and
      colony stimulating factor 1. These proteins, which appear to be ancestrally
      related, are hematopoietic growth factors that stimulate cells via specific and
      structurally related tyrosine kinase receptors on the cell surface.

PMID- 7566978
TI  - p16 proteins from melanoma-prone families are deficient in binding to Cdk4.
AB  - The tumor suppressor candidate p16INK4 is a cyclin-dependent kinase inhibitor
      that inhibits cell proliferation. The p16 coding gene is often mutated in
      glioblastomas, pancreatic adenocarcinomas and melanoma-prone pedigrees, but,
      until recently, the significance of these allelic variants has remained unclear.
      Here, we used interaction mating and coprecipitation to measure interaction of
      seven p16 allelic variants detected in melanoma-prone pedigrees with Cyclin
      dependent kinases (Cdks). We found that most variants were deficient in
      interaction with Cdk4 and Cdk6. One defective variant was found both in cancer
      prone families and in the control population and therefore previously defined as
      a common polymorphism. Another variant, which is weakly linked to familial
      cancer, is only slightly affected in interaction with Cdks. These results are
      consistent with the idea that p16 allelic variants that decrease Cdk interaction
      predispose individuals who carry them to an increased risk of cancer. Moreover,
      they suggest that determination of affinity between p16 mutants and partner
      proteins may help identify functionally-significant allelic variants not detected
      by classical human genetic techniques.

PMID- 7566979
TI  - Cell cycle gene expression and E2F transcription factor complexes in human
      melanoma cells induced to terminally differentiate.
AB  - Defects in cellular differentiation are a common occurrence in human cancers. The
      combination of recombinant human fibroblast interferon (IFN-beta) and the
      antileukemic compound mezerein (MEZ) results in an irreversible loss of
      proliferative capacity and terminal cell differentiation in H0-1 human melanoma
      cells. In contrast, either agent alone induces reversible growth arrest and/or
      specific components of the differentiation process without inducing terminal
      differentiation. The current study investigates changes in cell cycle, cell cycle
      gene expression and E2F transcription factor complex formation during the
      processes of reversible and irreversible (terminal) differentiation. Induction of
      both terminal differentiation and reversible differentiation (MEZ treatment)
      results in a temporal decrease in DNA synthesis and the percentage of cells in S
      phase and a decrease in the expression of cell cycle and growth regulated genes,
      including cdc2, cyclin A, cyclin B, histone H1, histone H4, nm23-H1, p53 and c
      myc. Persistent gene expression changes occur in terminally differentiated cells,
      but not in reversibly differentiated cells. H0-1 cells contain several E2F
      binding activities, including uncomplexed E2F, an E2F-p107-cyclin A-cdk2 kinase
      complex and an Rb-E2F complex. Induction of growth arrest by MEZ results in a
      slow migrating gelshift band that contains E2F associated with the pRb2/p130
      protein. There is also a loss of the Rb-E2F complex. Induction of terminal
      differentiation after treatment with IFN-beta + MEZ generates a second pRb2/p130
      E2F complex that migrates considerably faster than the pRb2/p130-E2F complex
      resulting from growth arrest. The slower migrating complex may contribute to
      growth arrest, whereas the faster migrating complex may play a role in terminal
      differentiation. Our results demonstrate that terminal cell differentiation
      involves a co-ordinate and continuous suppression of a number of cell cycle and
      growth related genes and results in the development of a novel E2F transcription
      factor complex not apparent in growth arrested and reversibly differentiated
      human melanoma cells.

PMID- 7566980
TI  - Expression of the receptor tyrosine kinase substrate genes eps8 and eps15 during
      mouse development.
AB  - Receptor tyrosine kinases (RTKs) control proliferation and differentiation
      through their ability to bind and/or phosphorylate intracellular substrates. The
      repertoire of substrates recruited by different RTK is largely overlapping. It is
      not clear, therefore, how a cell distinguishes among signals originating from
      different RTKs. One possibility is that selective availability of substrates
      participates in the regulation of this process. To gain insight into this issue,
      we studied the expression pattern, during mouse embryogenesis, of the eps8 and
      eps15 genes, which encode two recently identified RTK substrates. Both genes are
      expressed from E 10 in a restricted fashion. eps8 is first expressed in
      frontonasal neural crest-derived cells, in the mesenchyme of branchial arches and
      in the liver primordium. At E 12.5-E 14, eps8 is additionally expressed in the
      central nervous system (CNS) in a regional restricted pattern at the met
      mesencephalic transition area and in the developing submandibular salivary
      glands. eps15 is expressed at E 10 in the liver primordium, in the spinal ganglia
      and in the encephalic ganglia derived from the hindbrain neural crest. In
      addition, at E 12.5-E 14, eps15 is expressed, along all the CNS, in the
      ventricular zone where undifferentiated neuroblasts are located. The regional
      pattern of developmental expression of these two substrates sharply contrasts
      with their ubiquitous expression in adults, raising the possibility that their
      expression during embryogenesis is linked to selective proliferative and/or
      differentiative responses of specific neuroectodermal regions and body organs.

PMID- 7566982
TI  - RET/PTC oncogene activation is an early event in thyroid carcinogenesis.
AB  - RET/PTC oncogene activation occurs in about 20% of human thyroid papillary
      carcinomas. However, it is not known yet whether it is an early or late event in
      the process of thyroid carcinogenesis. Here we demonstrate, by using a combined
      immunohistochemical and reverse transcriptase-polymerase chain reaction based
      approach, that RET/PTC activation is present in 11 out of 26 occult thyroid
      papillary carcinomas analysed. Therefore, we conclude that it represents an early
      event in the process of thyroid cell transformation.

PMID- 7566981
TI  - A model of the G1 phase of the cell cycle incorporating cyclin E/cdk2 complex and
      retinoblastoma protein.
AB  - A mathematical model of cyclin E, cdk2 and retinoblastoma protein control of the
      G1 phase of the human cell cycle is proposed. The model includes retinoblastoma
      (Rb) protein phosphorylation by a cyclin E/cdk2 complex and its subsequent
      dephosphorylation at the end of the cell cycle. The numerical solutions to this
      model demonstrates the cyclic behavior of the cyclin E/cdk2 complex, with and
      without Rb function, cell cycle. This model suggests an inhibition of cyclin
      E/cdk2 complex formation (or its activation) by hypophosphorylated retinoblastoma
      protein. The experimental results of cell cycle arrest upon injection of
      transforming growth factor-beta, alpha-interferon or D-erythro-sphingosine during
      G1 phase are reproduced. Cell cycle behavior predicted by this model for
      increasing the concentration of hypophosphorylated retinoblastoma protein during
      the G1 phase is discussed. Additional results are obtained by numerical
      simulation.

PMID- 7566983
TI  - CDKN2 gene silencing in lung cancer by DNA hypermethylation and kinetics of
      p16INK4 protein induction by 5-aza 2'deoxycytidine.
AB  - Absent expression of the cyclin dependent kinase-inhibitor, p16INK4, is observed
      in a wide range of primary human cancers. Although homozygous deletions and point
      mutations have been reported in a subset of these tumors, the molecular basis for
      absent p16INK4 in other samples is unknown. We have examined 33 tumor cell lines
      and have shown that hypermethylation of a G:C-rich region within exon 1 of the
      CDKN2 gene was present in 100% of samples with wildtype RB expression and no
      detectable CDKN2 mutations. Treatment for at least 4 hours with the demethylating
      agent 5-aza 2'deoxycytidine, but not 5-azacytidine or 6-azacytidine, induces the
      prolonged expression of p16INK4 protein in each of these samples following a
      discrete 24-48 hour lag period. Consistent with the hypothesis that
      hypermethylation of the CDKN2 gene is a tumor-specific mechanism for gene
      inactivation, we observed hypomethylation at the exon 1 site exclusively in tumor
      lines that expressed p16INK4 or that had sustained inactivating point mutations
      within the CDKN2 open reading frame. These findings demonstrate a link between
      DNA methylation and the p16INK4:RB tumor suppressor pathway.

PMID- 7566985
TI  - Can amphotericin-B and blood components be given simultaneously.

PMID- 7566984
TI  - Practice alert: FDA approves Zinecard.

PMID- 7566986
TI  - Advanced certification examination challenging but not insurmountable.

PMID- 7566987
TI  - [Efficiency of surgical treatment in patients with laryngeal cancer in four
      clinical centers].
AB  - A group of 578 patients with larynx cancer underwent surgical treatment in four
      Otolaryngological Clinics of Medical Universities in Poznan, Warsaw, Cracow and
      Lublin between 1986-1987. Within this group, 75% of operated patients had a three
      -year survival rate without symptoms, and 58% of patients had a five-year
      survival rate. A detailed evaluation of causes of failures in surgical treatment
      dealt with e.g. the initial placement of the cancer including entrance margins of
      larynx in a rich net of lymphatic vessels, extensiveness of organs, the degree of
      clinical progressions, general physical condition of a patient, radicality of
      treatment, regularity of check-ups after the operation, high degree of
      histological malignancy unfavourable configuration of TNM feature blood
      transfusions, the appearance of remote metastases low efficiency in the early
      diagnostics of larynx cancer, subjective conditions of patients, discontinuation
      of complementary irradiation.

PMID- 7566988
TI  - [Patency restoration of the obliterated larynx].
AB  - Two cases of total subglottic stenosis of the larynx and of the upper segment of
      the trachea following an automobile accident and a prolonged endotracheal
      intubation are presented. Both were observed in ENT Department of Pomeranien
      Medical Academy in Szczecin during the years 1991-1992. In both cases the ring of
      the cricoid cartilage and upper segment of trachea was excised and the primary
      thyrotracheal anastomosis was performed. The functional results of the treatment
      in either case was satisfactory.

PMID- 7566989
TI  - [Application of intralaryngeal submucous chordectomy in the treatment of
      bilateral vocal cord paresis].
AB  - The article presents long-term results of operative treatment of 128 patients
      with bilateral vocal cord paresis. The best functional results, for all the 128
      operated cases, were obtained with the use of the method of intralaryngeal
      submocous chordectomy, with partial arytenoidectomy performed according to the
      technique of laryngeal microsurgery. However, considerably poorer results were
      obtained in those cases where the classic Surjan method was used, or our own
      modifications of this method.

PMID- 7566990
TI  - [Clinical analysis of indications to ventilation tube removal in otitis media
      with effusion].
AB  - The indications to ventilations tube removal in otitis media with effusion based
      on the own material and other authors suggestions were defined. The necessity of
      the tube removal in the case when it hasn't extruded itself after recovery was
      pointed out. Special conditions were defined in such cases. The necessity of the
      ventilations tube removal in otitis media with effusion during developing
      complications, such as tube displacement into middle ear, granulation tissue
      around the tube, otorrhea, blocked lumen of a tube that cannot be opened by
      alternative means, was also emphasized.

PMID- 7566991
TI  - [Otitis media with effusion in children].

PMID- 7566992
TI  - [The influence of nasopharyngeal obstruction on gasometric parameters in
      children].
AB  - The examinations were performed before and one month after adenoidectomy
      Comparison of the obtained results did not show significant changes in gasometric
      results due to operation. No correlation also was shown between the weight of the
      adenoid and changes in gasometric parameters after operation. In all children the
      improvement in clinical stage after operation was observed. Based on obtained
      results it seems that about nasopharyngeal obstruction in children with enlarged
      adenoid decides not its weight (size) only but the ratio between its size and
      nasopharyngeal capacity.

PMID- 7566993
TI  - [Cytology of nasal polyps].
AB  - Cytograms were made from polyps and nasal mucosa in 30 patients suffering from
      chronic rhinitis and polyps. A semiquantitative method described in
      Otolaryngologia Polska in 1985 year was used. In 6 cytograms taken from polyps,
      neutrophils were found on an average in 93% of observed cells. In 24 cytograms
      the predominance of eozynophils was found on an average of 49%. In cytograms with
      predominance of eozynophils, basophils were found on an average of 13%. These
      results allowed the etiology to be distinguished and either pharmacological or
      surgical treatment to be applied, versus hitherto applied surgical treatment. In
      6 eozynophilic patients cytograms were made from the mucosa 2 weeks after
      polypectomy. A considerable decrease or total disappearance of eozynophilic and
      basophilic cells was found.

PMID- 7566994
TI  - [Otoneurological aspects of tick-borne encephalitis].
AB  - In analysed material of 31 patients with TBE (tick borne encephalitis) we noticed
      symptoms evidence the impact of TBE virus vestibular system. We showed that 21
      patients had disorders like dizziness and lack of balance. And 11 patients had
      inaudility of conductive and receiving type what was the evidence of injury of
      vestibular nerve. In these 11 patients we observed not normal recording of
      optokinetical reaction.

PMID- 7566995
TI  - [Transitory evoked otoacoustic emissions in children with impaired middle ear
      ventilation].
AB  - Transient evoked otoacoustic emission (TEOAE) has proven to be a useful clinical
      screening test for auditory dysfunction. Problems concerning the evaluation are
      mainly due to irregularities of the physiological middle ear functions. In this
      study different degrees of middle ear alterations were quantified by means of
      tympanometry, otoscopy and pure-tone audiometry and then related to the results
      of TEOAE registration which were classified by the coefficient of the cross
      correlation and the frequency response spectrum. Data were obtained from 82 ears
      of 41 children between the age of 3 and 7 years. When children displayed a
      tympanogram with no observable peak, a successful registration of TEOAE was
      possible in only 10.5% (n = 19) of the cases. Such results are related to serous
      or mucoid effusions which probably prevent a transmission of the emission from
      the cochlea to the meatus. In analysing the related between conductive losses in
      pure-tone audiometry and TEOAE it was demonstrated that no TEOAE was could be
      recorded in ears with a conductive loss above 20 dB HL. This study emphasizes the
      need to reexamine children who do not show positive emissions connected with
      middle ear imbalances. Only by retesting these children is it possible to
      determine whether or not cochlear lesions or middle ear problems prevent a
      positive TEOAE registration.

PMID- 7566996
TI  - [The usefulness of impedance audiometry for the diagnosis of occupational hearing
      loss].
AB  - The use of impedance audiometry for determining hearing threshold and locating
      hearing impairments was investigated in 112 people exposed to occupational noise.
      Tympanometry and the stapedius reflex threshold measurements (ART) were made
      using Madsen ZO 2020 set. The comparison of ART findings, particularly the
      interval between tonal audiometric threshold and stapedius reflex threshold,
      helped to diagnose cochlear location of hearing impairment in 17 subjects (15.2%)
      and extracochlear in 70 (62.5%) out of all the examined subjects. The analysis of
      the study results has confirmed the usefulness of impedance audiometry also when
      patients' simulation has to be excluded in the case of their claiming
      compensation for occupational hearing loss.

PMID- 7566997
TI  - [Pseudocyst of the upper part of the thyreoglossal duct coexisting with
      congenital anomalies (Rokitansky-Kustner-Mayer syndrome and Barlow syndrome)].

PMID- 7566998
TI  - [Perforation of the cervical part of esophagus].
AB  - Authors present the case of the perforation of the cervical part of the esophagus
      caused by the foreign body (bone). Patient was successfully treated despite of
      the delayed diagnosis and primary management.

PMID- 7566999
TI  - [Metastasis of colon cancer to the larynx: a case report].
AB  - A 52 years-old male was accepted to the ENT Department because of hoarseness
      lasting for three month. According to the case history, in 1990 he underwent the
      anterior resection sigmorecti due to carcinoma. Preliminary histopathological
      specimen examinations performed in our department twice, suggested chronic,
      fibrotic laryngitis. Another histopathological examination carried out during
      surgical procedure of the prelaryngeal region opening, showed pictures
      characteristic for metastatic tumor.

PMID- 7567000
TI  - [Congenital atresia of the anterior nares and hypoplasia of the nasal cavity].
AB  - We described a case of congenital atresia of the anterior nares with a minute
      opening on the right side and underdevelopment of the nasal cavities. The hard
      palate was flat and the soft palate was normally mobile. Right anophthalmia and
      microphthalmia of the left eye with iris coloboma were also noted. In order to
      provide a nasal airway and to enable the newborn to suck and breathe
      simultaneously the patient was operated on at four days of age. By means of
      transpalatal approach a nasal cavity was drilled out of solid bone and connected
      with the small anterior duct. Trough the new created air duct a nasopharyngeal
      tube was introduced. In spite of that the external nasal orifice was enlarged
      later, there was an inclination the orifice to collapse due to lack of nostril
      cartilages, therefore a nasopharyngeal tube still is used. The physical and
      intellectual development of the now 11-month old infant is normal. Final
      reconstruction of the external nose will take place later.

PMID- 7567001
TI  - [Damage from passive tobacco smoking].
AB  - The author presents data on the biological casualties and consequences of tobacco
      smoking. Smoking is the most dangerous addiction in the scale of the world and in
      Poland. It causes numerous premature decrease and tobacco-dependent sickness. The
      author characterises the spread of this addiction in Poland concentrating on the
      problem of the passive smoking harmfulness. Non-smokers, children and youth,
      embryo and foetus during the pregnancy are exposed to the passive smoking. The
      experimental examinations of animals and the analysis of the lateral stream of
      the tobacco smoke confirm not the least, but rather the greater damage of the
      passive smoking than the active one. The mechanisms of acting of the tobacco
      smoke on the passive smokers' body and the health consequences are discussed. The
      manners, means and activities that are useful for the health protection of non
      smokers against the tobacco smoke and the ways of the smoking prevention are
      described.

PMID- 7567002
TI  - Technology transfer: where to begin.

PMID- 7567003
TI  - Sound pressure gain produced by the human middle ear.
AB  - The acoustic function of the middle ear is to match sound passing from the low
      impedance of air to the high impedance of cochlear fluid. Little information is
      available on the actual middle ear pressure gain in human beings. This article
      describes experiments on middle ear pressure gain in six fresh human temporal
      bones. Stapes footplate displacement and phase were measured with a laser Doppler
      vibrometer before and after removal of the tympanic membrane, malleus, and incus.
      Acoustic insulation of the round window with clay was performed. Umbo
      displacement was also measured before tympanic membrane removal to assess
      baseline tympanic membrane function. The middle ear has its major gain in the
      lower frequencies, with a peak near 0.9 kHz. The mean gain was 23.0 dB below 1.0
      kHz, the resonant frequency of the middle ear; the mean peak gain was 26.6 dB.
      Above 1.0 kHz, the second pressure gain decreased at a rate of -8.6 dB/octave,
      with a mean gain of 6.5 dB at 4.0 kHz. Only a small amount of gain was present
      above 7.0 kHz. Significant individual differences in pressure gain were found
      between ears that appeared related to variations in tympanic membrane function
      and not to variations in cochlear impedance.

PMID- 7567004
TI  - Papillary carcinoma of the thyroid.
AB  - Between 1954 and 1993 503 patients with papillary carcinoma of the thyroid were
      treated at the Department of Otolaryngology-Head and Neck Surgery of the
      Beilinson Medical Center. Two thirds of these patients were women. The median
      follow-up period was 10.3 years. In more than 30% of cases the tumor was
      discovered because of the presence of an enlarged lymph node and/or invasion to
      adjacent structures. Total or near-total thyroidectomy was performed in 381
      patients. The 48 patients in whom it was necessary to perform a reoperation had a
      significantly higher complication rate. Multicentricity was found in 65% of those
      cases in which both thyroid lobes were available for histologic examination.
      Nineteen patients were found to have a "tail" cell variant, 223 had a pure
      papillary variant, and 261 a follicular variant. The mortality rate was 6.2% 15
      years after initial therapy. A number of factors-age, size of tumor, presence of
      distant metastases, "tall" cell variant, and type of surgery-were found to be
      significant predictors of survival. After almost 40 years of experience in
      treating more than 500 cases of papillary cancer, we have come to the conclusion
      that the surgical approach should be aggressive.

PMID- 7567006
TI  - Intranasal anesthetic effects of lidocaine and tetracaine compared.
AB  - The quality of nasal anesthesia obtained with two local anesthetic solutions (2%
      lidocaine in oxymetazoline and 1% tetracaine in oxymetazoline) was evaluated in
      this double-blind, randomized study. Each local anesthetic mixture was applied to
      the nasal septum of healthy volunteers with medication-soaked pledgets.
      Measurements of anesthetic effect (sensation threshold and pain perception) were
      made with Semmes-Weinstein monofilaments (North Coast Medical, San Jose, Calif.).
      Measurements were performed before local anesthetic application and at 10 and 70
      minutes after local anesthetic application. Subjects had greater increases in
      sensation threshold with tetracaine than with lidocaine at both 10 and 70 minutes
      (p = 0.0005 and p = 0.0001, respectively). Subjects had greater decreases in pain
      perception with tetracaine than with lidocaine at both time intervals (p = 0.0003
      and p < 0.0001, respectively). Tetracaine mixed with oxymetazoline appears to be
      a superior topical anesthetic for nasal procedures.

PMID- 7567005
TI  - Role of gastroesophageal reflux disease in patients with cervical symptoms.
AB  - Otolaryngologists commonly see patients with various nonspecific upper
      aerodigestive or "cervical" symptoms. The relationship between gastroesophageal
      reflux disease and these symptoms has been studied but remains unclear. We
      reviewed the records of 216 patients with various cervical symptoms. Each patient
      underwent a uniform investigation that included barium swallow, esophageal
      manometry, acid stimulation testing, and esophagoscopy with distal biopsy.
      Patients were treated with a combination of a histamine H2 blocker or omeprazole
      and a prokinetic agent. Follow-up was obtained in 194 patients. Overall, evidence
      of gastroesophageal reflux disease was detected in 73% of patients. Complete
      resolution or improvement of symptoms was seen in 84% of patients with treatment.
      We believe gastroesophageal reflux disease is an important factor in the cause of
      cervical problems.

PMID- 7567007
TI  - Effect of epidermal growth factor on tympanic membranes with chronic
      perforations: a clinical trial.
AB  - Epidermal growth factor is an important modulator of cell growth, and its role in
      normal wound healing is well documented. Epidermal growth factor receptors have
      been identified in tympanic membranes of different animals. The ability of
      epidermal growth factor to promote healing of tympanic membrane perforations has
      recently been shown in experimental animals. We performed a double-blind, placebo
      controlled study of the effect of epidermal growth factor applied locally on the
      tympanic membrane for 1 week in patients with chronic perforations. Seventeen
      adult patients took part in the study, eight in the epidermal growth factor group
      and nine in the placebo group. Three placebo-treated patients were later treated
      with epidermal growth factor, and five patients received repeated epidermal
      growth factor treatment. Perforation size was measured as a percentage of the
      tympanic membrane area before and at least 1 month (mean, 2.6 months) after
      treatment. One perforation in the placebo group healed completely, but none of
      the epidermal growth factor-treated perforations closed. Perforations became
      slightly smaller in both groups (mean decrease, 0.3% and 2.7% for epidermal
      growth factor and placebo, respectively), but these changes in size were not
      statistically significant for either group. At otomicroscopy, a proliferation
      reaction with thickening of the tympanic membrane and pseudomembrane formation at
      the perforation edge could be seen in some ears. Histologically, a sample from
      one epidermal growth factor-treated ear demonstrated signs of hypertrophic
      epithelium when compared with the morphology of a placebo-treated tympanic
      membrane. The only complications were two mild infections in the placebo group.
      Hearing remained stable after epidermal growth factor treatment.

PMID- 7567008
TI  - Pediatric tympanoplasty: the role of adenoidectomy.
AB  - A chronic dry perforation in a child presents a dilemma with regard to timing of
      intervention or whether intervention is appropriate at all. Many studies have
      looked at elements associated with eustachian tube function in hopes of finding
      prognostic factors. Adenoidectomy has been shown to be very effective in the
      treatment of chronic and recurrent otitis media. Intuitively, it would seem to
      play a role in pediatric tympanoplasty; however, no study has thoroughly
      investigated this issue to date. To evaluate the role of adenoidectomy in
      pediatric tympanoplasty, we performed a retrospective review of all patients
      younger than 18 years who had a simple dry perforation and underwent a
      Wullstein's type I tympanoplasty. Thirty-six patients were identified for review
      during the 7-year study period. The patients were grouped into those who had
      previous adenotonsillectomy (n = 12), those who had prior adenoidectomy alone (n
      = 10), and those who had neither (n = 14). Initial success of tympanoplasty was
      noted to be high in all three groups. However, at 6-month follow-up, the success
      for the group who had not had prior adenoidectomy or tonsillectomy dropped
      dramatically (14.3%), whereas the other two groups maintained success rates in
      excess of 75% (p = 0.002). This relationship remained fairly constant throughout
      the 2 years of follow-up. Although our population under study is somewhat small,
      the results support a potentially advantageous role of adenoidectomy for
      pediatric tympanoplasty. These results and their implications will be discussed.

PMID- 7567009
TI  - Transcutaneous cervical miniesophagostomy.
AB  - Nasogastric tubes have been shown to cause damage to the pharyngolaryngeal
      complex, producing laryngeal inflammation, granulation, muscle damage, and even
      vocal cord immobility. The coexistence of nasogastric and tracheotomy tubes after
      conservation laryngeal surgery is especially harmful. The friction between these
      two semirigid structures may result in damage to the remaining part of the
      larynx. This may result in a significant delay in healing, oral feeding, and
      decannulation. Percutaneous endoscopic gastrostomy is a possible solution. This
      procedure requires time, special expertise, and cooperation between services. We
      present our experience with 17 transcutaneous cervical miniesophagostomies using
      a small-caliber feeding tube, which were performed during conservation laryngeal
      and/or pharyngeal surgery. The rate of minor complications was 11.7%, or 0.40
      complications per 100 tube days, and no major complications were related to the
      procedure. Transcutaneous cervical miniesophagostomy is a simple and quick
      procedure that may be performed during the primary cancer surgery. It is done by
      the head and neck surgeon and does not require special expertise. It takes about
      5 minutes to perform and, if done correctly with funneling under skin flaps, is
      associated with minimal or no postoperative morbidity.

PMID- 7567011
TI  - Liposuction-assisted excision of cervicofacial lipomas.

PMID- 7567010
TI  - Transoral-transpharyngeal approach to the craniocervical junction.
AB  - The transoral-transpharyngeal approach is a reliable and technically sound method
      for gaining anterior extradural exposure to the craniocervical junction. We
      report 23 patients undergoing this approach for pathology lying between the
      inferior clivus and third cervical vertebra. Pathology included 6 patients with
      congenital malformations of the odontoid process, 4 patients with basilar
      invagination caused by rheumatoid arthritis, 2 patients with atlantoaxial
      subluxation caused by Down's syndrome, and 1 each with Chiari I malformation,
      pseudogout of C1/C2, ossification of the posterior longitudinal ligament, and
      chronic dens dislocation caused by trauma. Malignant tumors included 4 chordomas,
      2 giant cell tumors of C1-C3, and 1 chondrosarcoma. Orotracheal intubation
      without tracheotomy was used in 22 patients. Sixteen of these 22 patients were
      extubated either immediately or within 24 hours. Six complications occurred in 5
      patients and included a palatal dehiscence in 2, delayed oropharyngeal
      hemorrhage, prolonged endotracheal intubation because of severe tongue edema, and
      1 case each of meningitis and aspiration pneumonia responsive to intravenous
      antibiotics. No deaths, local infections, or postoperative cerebrospinal fluid
      leaks occurred. Neurologic symptoms of cord compression improved or stabilized in
      all patients. The transoral-transpharyngeal approach is an effective means for
      extradural decompression of the anterior craniocervical junction and for exposure
      of selected tumors at this site.

PMID- 7567013
TI  - Overexpression of p53 predicts organ preservation using induction chemotherapy
      and radiation in patients with advanced laryngeal cancer. Department of Veterans
      Affairs Laryngeal Cancer Study Group.
AB  - A critical research frontier in head and neck oncology involves defining the use
      of induction chemotherapy regimens to allow organ preservation and to avoid
      functionally debilitating surgical resections. Completed clinical trials in
      laryngeal cancer indicate that such an approach is feasible, but progress thus
      far has been limited by our inability to predict which patients are likely to
      respond to chemotherapy and preserve their larynx. Mutation of the p53 tumor
      suppressor gene is the most common genetic alteration identified thus far in
      human cancers, and it may be important in regulation of cell proliferation and
      chemosensitivity. To determine whether p53 overexpression predicts chemotherapy
      response, organ preservation, and survival in patients with advanced laryngeal
      cancer, we analyzed immunohistologic expression of p53 in tissue sections from
      178 patients with advanced laryngeal cancer who were entered in the Department of
      Veterans Affairs Laryngeal Cancer Cooperative Study, a multiinstitutional
      clinical trial comparing induction chemotherapy (cis-platinum and 5-fluorouracil)
      plus radiation therapy (94 patients) to surgery plus postoperative radiation
      therapy (84 patients). Larynx preservation was significantly higher in the group
      of patients whose tumors overexpressed p53 (74% vs. 52.5%; p = 0.03). The
      presence of p53 overexpression did not predict survival in either the surgery or
      the chemotherapy groups (p = 0.82 and p = 0.53).

PMID- 7567012
TI  - Positron emission tomography in the detection of residual laryngeal carcinoma.
AB  - Positron emission tomography measures the metabolic activity of tissue. Because
      metabolism rates are higher in tumors than in normal tissue, positron emission
      tomography can be used to identify abnormal tissue. Positron emission tomography
      has proved useful in detecting residual or recurrent tumor in the brain and
      gastrointestinal tract after definitive treatment. We selectively used positron
      emission tomography in a preliminary trial to examine patients with laryngeal
      cancer who had previously been treated with organ-preservation therapy with
      radiation therapy alone or in combination with induction chemotherapy. These
      patients are often difficult to examine both clinically and radiographically
      because of posttreatment edema and fibrosis. From 1991 to 1993 patients at our
      institution who were treated with either radiation therapy or a combination of
      induction chemotherapy and radiotherapy for laryngeal carcinoma were evaluated
      after treatment. If clinical examination was suspicious for residual tumor or
      recurrence, a computed tomography or magnetic resonance imaging scan was
      obtained. In 10 patients neither clinical examination nor conventional imaging
      could absolutely rule out residual/recurrent carcinoma. In these patients
      positron emission tomography with 2-fluoro-2-deoxy-D-glucose was used to detect
      disease. The results from positron emission tomography were compared with the
      results from subsequent biopsy (five patients) or clinical follow-up. Positron
      emission tomography had a sensitivity of 67% and a specificity of 57%. The
      positive predictive value of positron emission tomography was 67%. The negative
      predictive value of positron emission tomography was 80%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7567015
TI  - Ossiculoplasty with polymaleinate ionomeric prosthesis.
AB  - With the continued concern over the possible transmission of viral infections
      through homologous middle ear implants, there is increasing pressure to develop a
      truly biocompatible alloplastic middle ear prosthesis. The polymaleinate ionomer,
      which has been used in dentistry as a filling and luting material for more than
      15 years, has recently been used to construct total and partial ossicular
      replacement prostheses. In an attempt to evaluate these new implants, a
      multicenter prospective clinical trial was initiated. To date, 92 patients have
      undergone implantation. The follow-up interval ranged from 3 months to 22 months.
      Although it is premature to discuss the long-term results, the preliminary
      surgical experience and audiometric data with these implants are reviewed. From a
      surgical perspective, the ionomeric prostheses were easily contoured with a
      diamond burr and were not prone to shattering. Preliminary follow-up audiometric
      data were available on 80 patients (59 partial ossicular replacement prostheses
      and 21 total ossicular replacement prostheses). Of the 59 partial ossicular
      replacement prostheses the air-bone gaps (average of 500 Hz, 1 kHz, 2 kHz and 3
      kHz) were as follows: 0 dB to 10 dB, 15 (25%) of 59; 11 dB to 20 dB, 20 (34%) of
      59; 21 dB to 30 dB, 11 (19%) of 59; and greater than 30 dB, 13 (22%) of 59. Of
      the 21 total ossicular replacement prostheses the air-bone gaps were as follows:
      0 dB to 10 dB, 6 (29%) of 21; 11 dB to 20 dB, 6 (29%) of 21; 21 dB to 30 dB, 5
      (24%) of 21; and greater than 30 dB, 4 (19%) of 21.

PMID- 7567014
TI  - Effect of partial middle turbinectomy on nasal airflow and resistance.
AB  - We report the first prospective study of the effect of partial middle
      turbinectomy on nasal airflow and resistance as measured objectively by active
      anterior rhinomanometry. Our study group consisted of 31 consecutive patients who
      underwent functional endoscopic sinus surgery with simultaneous partial middle
      turbinate resections. We found that all patients had significant improvement in
      nasal airflow (p < 0.001) and significant decrease in nasal resistance (p <
      0.001). Thus we found no deleterious effect on nasal function. Additionally, we
      reviewed the literature on retrospective series in which patients had received
      partial middle turbinectomies and found no evidence that nasal function was
      impaired after surgery. We conclude that partial middle turbinectomy may be
      performed without adversely altering nasal function, as measured by active
      anterior rhinomanometry.

PMID- 7567016
TI  - Modified transnasal endoscopic Lothrop procedure as an alternative to frontal
      sinus obliteration.
AB  - Persistent frontal sinusitis traditionally has been treated with external
      procedures such as osteoplastic frontal sinus obliteration or the Lynch
      procedure. Currently, functional endoscopic sinus surgery can be used in most
      cases to remove disease from the frontal recess, the most frequent site of
      frontal sinus obstruction, thereby relieving the sinusitis. In some cases,
      however, frontal recess exploration has failed to relieve the obstruction of the
      frontal sinus, necessitating an osteoplastic frontal sinus obliteration. We
      present our experience with a transnasal modification of the Lothrop procedure.
      The Lothrop procedure, first described in 1914, uses a combined external and
      transnasal approach to resect the median frontal sinus floor, superior nasal
      septum, and intersinus septum to drain the frontal sinus. This procedure was
      largely abandoned and forgotten by modern otolaryngologists. However, with the
      advent of the computed tomography scan and endoscopic techniques, we sought to
      reassess the basic tenant of the Lothrop procedure (i.e., wide median frontal
      sinus drainage). An anatomic study of cadaver heads was performed to quantify the
      surprisingly large potential opening and to better understand the pertinent
      anatomy. This procedure was performed on 10 patients, with no resulting
      complications and no failure to maintain patency of the frontal sinus drainage
      throughout the follow-up period (mean, 7 months). We are encouraged by our
      initial favorable results and intend to use the procedure in the future as needs
      arise.

PMID- 7567019
TI  - Management guidelines for improvement of otolaryngology referrals from primary
      care physicians.
AB  - OBJECTIVE AND DESIGN: A prospective evaluation of the effectiveness of
      otolaryngology evaluation, treatment, and referral guidelines developed
      collaboratively by otolaryngologists and primary care physicians on referrals and
      access to otolaryngology. Comparisons of appropriate to unnecessary referrals,
      the percentage of patients referred with disorders addressed to those without
      disorders addressed in the guidelines, access to otolaryngology, and
      questionnaire evaluations of primary care physician and patient satisfaction were
      measured before and after guideline implementation. RESULTS: A significant
      decrease in appropriate to unnecessary referrals was seen, from 55% before to 12%
      after guidelines. The percentage of patients seen within 1 month of scheduling
      improved from 39% to 59%. Guideline-addressed disorders decreased from 63% to
      40%. The need for patients to see another physician for the referred symptom
      while waiting to see an otolaryngologist decreased from 31% to 3%. Patient
      satisfaction with wait times improved. Eighty-six percent of the primary care
      physicians used the guidelines, and 85% wanted to expand the guidelines to other
      specialty areas. CONCLUSIONS: Management and referral guidelines are effective in
      improving patient access and the ratio of appropriate to unnecessary referrals.
      Such guidelines are well accepted and used by primary care practitioners in this
      setting.

PMID- 7567017
TI  - Juvenile nasopharyngeal angiofibroma and familial adenomatous polyposis: an
      association?
AB  - Juvenile nasopharyngeal angiofibroma is a benign neoplasm affecting the
      nasopharynx of male adolescents. Two patients treated at Temple University
      Hospital for this condition were also diagnosed with familial adenomatous
      polyposis. Familial adenomatous polyposis results from the inheritance of a
      mutated adenomatous polyposis coli gene in an autosomal dominant pattern. The
      development of colorectal carcinoma in middle age is seen almost invariably in
      familial adenomatous polyposis, if a prophylactic colectomy is not performed. To
      identify a possible association between juvenile nasopharyngeal angiofibroma and
      familial adenomatous polyposis, chart reviews and patient interviews were carried
      out for all patients treated for juvenile nasopharyngeal angiofibroma at Temple
      University Hospital between 1985 and 1993. Single-strand conformational
      polymorphism was performed to detect the presence of certain adenomatous
      polyposis coli gene mutations within the germline DNA of those juvenile
      nasopharyngeal angiofibroma patients not previously found to have familial
      adenomatous polyposis. Although no more patients with both juvenile
      nasopharyngeal angiofibroma and familial adenomatous polyposis were found by
      these methods, the two patients with both disorders previously identified
      constitute 22% of our juvenile nasopharyngeal angiofibroma series. The
      implications of these findings are discussed.

PMID- 7567018
TI  - Symptom outcome after functional endoscopic sinus surgery in patients with cystic
      fibrosis: a prospective study.
AB  - Twenty-nine consecutive patients with cystic fibrosis were offered functional
      endoscopic sinus surgery. Twenty-six of these patients underwent surgery. A
      symptom questionnaire was obtained from the patient or parent before surgery. At
      the end of the study this symptom questionnaire was again administered to the
      same individual, and 21 completed it. There were 14 male and 7 female patients,
      with a mean age of 12.3 years and a median age of 8.7 years. Mean follow-up was
      34.3 months. Results for the following symptoms were significant: nasal airway
      obstruction was improved (p < 0.0002), olfactory function was improved (p <
      0.0037), purulent nasal discharge was decreased (p < 0.001), and activity level
      was increased (p < 0.001). Other parameters are also reported in the text. In
      summary, this study prospectively studies the effects of functional endoscopic
      sinus surgery on symptoms in patients with cystic fibrosis. The study points out
      several significant areas of symptom improvement and supports the selective use
      of functional endoscopic sinus surgery in patients with cystic fibrosis.
      Indications for surgery are provided.

PMID- 7567021
TI  - Laser vestibulectomy for endolaryngeal neurofibroma.

PMID- 7567020
TI  - Carbon dioxide laser occlusion of the guinea pig posterior semicircular canal.
AB  - Preservation of hearing is possible with selective ablation of the vestibular
      system and mechanical occlusion of the semicircular canals. Complete ablation of
      all three canals would improve exposure of the internal auditory canal fundus
      (e.g., for acoustic tumor exposure), but mechanical packing of the vestibule
      would disrupt normal sound transduction. This study was designed to assess the
      feasibility of preserving hearing with CO2 laser occlusion, without mechanical
      packing of the posterior semicircular canal membranous labyrinth. Twenty adult
      Hartley guinea pigs underwent occlusion of the right posterior semicircular canal
      with one of three techniques: mechanical packing, laser coagulation, or laser
      coagulation with mechanical packing. Electrocochleographic thresholds to clicks
      and 1-kHz and 8-kHz tone bursts did not change significantly 6 weeks after
      posterior semicircular canal occlusion with any of these techniques.
      Histopathologic examination revealed complete canal occlusion with all methods.
      These findings suggest that mechanical occlusion and CO2 laser occlusion of the
      posterior semicircular canal do not significantly affect cochlear function in the
      guinea pig. CO2 laser occlusion of the membranous labyrinth may prove useful for
      more extensive selective vestibular ablation by obviating the need for mechanical
      packing of the labyrinth.

PMID- 7567022
TI  - Giant lymph node hyperplasia of the head and neck (Castleman's disease): a report
      of five cases.

PMID- 7567023
TI  - Necrotizing fasciitis originating from pinna perichondritis.
AB  - NF is a potentially lethal infectious process usually found in the abdomen,
      perineum, or extremities. In the head and neck it usually starts from a dental
      infection but can be initiated from any source. One of the more serious sequelae
      is extension of the infection down the deep fascial planes of the neck leading to
      mediastinitis; this is associated with a higher mortality rate. The presence of
      an associated immunocompromising disease, such as diabetes, has been said to
      predispose an individual to NF, and the mortality rate has been shown to be
      higher (although perhaps not significantly so). When first described, NF was
      thought to be caused only by beta-hemolytic Staphylococcus. Now it known to be a
      polymicrobial infection with anaerobes and facultative anaerobes found most
      frequently. Treatment involves broad-spectrum intravenous antibiotics as soon as
      possible, narrowing the coverage as the results of the gram stain and cultures
      become available. The importance of aggressive, prompt surgical management cannot
      be overemphasized in the treatment of NF. Once the diagnosis of NF is strongly
      suspected, debridement of the affected areas must be accomplished as soon as
      possible. Despite the advances in the recognition and treatment of NF, there is
      still significant morbidity and mortality associated with this disease. Continued
      vigilance must be practiced if the survival rate is to continue to increase.

PMID- 7567024
TI  - Malignant transformation of nasopharyngeal lymphoid hyperplasia.
AB  - Lymphadenopathy and nasal obstruction are very common in the HIV-positive patient
      and may or may not reveal a nasopharyngeal tumor. Biopsy is warranted if there is
      evidence suggestive of lymphoma or other neoplastic disease. This would include
      progressive rapid enlargement observed on examination or CT scan, an asymmetric
      growth pattern, and evidence of invasion of normal anatomic boundaries. It is
      certain that not all cases of adenoid hypertrophy that occurs early in the course
      of HIV disease represent a malignancy. Further study is needed to determine the
      proper timing for nasopharyngeal biopsy in the HIV-positive population. As the
      life span of the HIV-positive patient increases, so may the incidence of
      malignant degeneration.

PMID- 7567025
TI  - Primary cryptococcal infection of the larynx: report of a case.

PMID- 7567026
TI  - Congenital nasolacrimal duct cysts with nasal obstruction.

PMID- 7567028
TI  - Tracheocele after routine tracheostomy.

PMID- 7567027
TI  - Traumatic retropharyngeal hematoma: a case report.
AB  - We describe a case of retropharyngeal hematoma after a cervical hyperextension
      injury in an elderly man. Progressive hoarseness, dysphagia, and dyspnea were the
      early signs that necessitated oral endotracheal intubation and, ultimately,
      tracheostomy. The hematoma was explored and drained through a lateral cervical
      approach, and a bleeding vessel in a small tear in the anterior spinous ligament
      was noted and cauterized. The patient recovered uneventfully.

PMID- 7567029
TI  - Massive hematoma resulting in bilateral hypoglossal nerve paralysis.

PMID- 7567030
TI  - Ethmoid sinus leiomyosarcoma after cyclophosphamide treatment.

PMID- 7567031
TI  - Bilateral sensorineural hearing loss as a first symptom of chronic myelogenous
      leukemia.

PMID- 7567032
TI  - Laryngeal mask airway.

PMID- 7567034
TI  - Is the AMA losing perspective?

PMID- 7567033
TI  - Bottleneck entrapment of the tongue.

PMID- 7567035
TI  - The job's not over till the paperwork's done.

PMID- 7567036
TI  - Coping with kaleidoscopic change.
AB  - Nearly 300 people attended the Society's annual Leadership Conference, held May 2
      3, 1995, at the Harrisburg Hilton and Towers. This year's theme, "Coping with
      Kaleidoscopic Change," was developed by the Leadership Conference Committee to
      portray the constantly changing images of the health care marketplace in
      Pennsylvania, as well as nationwide. As one committee member explained, "As
      images change with only the slight bump of the hand, we see ourselves readying to
      move with those images, and also being prepared for what might be the next
      image." One medical journalist, one medical leader, one medical academician, and
      one federation representative offer their perspectives in this recap.

PMID- 7567037
TI  - Patients equate quality with service.

PMID- 7567038
TI  - FDA certification required for mammography claims.

PMID- 7567039
TI  - Transplant drug coverage changes.

PMID- 7567040
TI  - Volunteers sought to help train more generalists.

PMID- 7567042
TI  - Diagnosing, treating depression in the elderly.
AB  - Depression is a clinical syndrome prevalent in older adults. In this article,
      David Greenspan, MD, coh-chair of the Psychiatric Physicians of Pennsylvania's
      Geriatric Psychiatry Committee, discusses the diagnosis and management of the
      depressed geriatric patient.

PMID- 7567041
TI  - A new approach to health system reform: seizing the moral high ground.
AB  - Has economic imperialism seduced physicians into viewing medicine as more of a
      business than a profession? Yes, says one State Society member. He proposes that
      doctors subordinate personal interests to the public interest, establishing a
      "Hoover Commission" to redesign health care.

PMID- 7567044
TI  - Spreading us thinner and thinner...

PMID- 7567043
TI  - Lyme disease: debilitating, yet preventable.

PMID- 7567045
TI  - KePRO's principal clinical coordinator.

PMID- 7567046
TI  - Thoughts from (and for) our new secretary of health. Interview by David Woods.

PMID- 7567047
TI  - Cult-proofing your patients: a guide to diagnosis, treatment, and referral of
      cult victims and survivors.

PMID- 7567048
TI  - Choosing your path to MEDLINE.
AB  - Competing vendors package the seven million article citations in MEDLINE in many
      different ways. When the information inside is the same, how can you tell solid
      value from just another pretty interface? This article, one in a series on
      medical information technology, discusses points to consider before making a
      commitment.

PMID- 7567050
TI  - Pennsylvania Medical Society membership directory. 1995-1996.

PMID- 7567049
TI  - Treatment of congestive heart failure: what's new?

PMID- 7567052
TI  - Understanding the limitations of vocational tests.

PMID- 7567051
TI  - Study recommends HIV counseling, testing, treatment of pregnant women.

PMID- 7567053
TI  - Each facility needs a workers' compensation committee.

PMID- 7567054
TI  - HOW TO AVOID A "tick"ing bomb.

PMID- 7567055
TI  - Tips on getting a good start in a new job.

PMID- 7567056
TI  - Automated scheduling.

PMID- 7567057
TI  - PNA position statement. The role of the licensed practical nurse (LPN).

PMID- 7567058
TI  - ANA on-line.

PMID- 7567059
TI  - Obtaining the most benefit from job advertisements.

PMID- 7567060
TI  - Nurses do even more as care changes.

PMID- 7567062
TI  - Characterization of immunoglobulin G-degrading proteases of Prevotella intermedia
      and Prevotella nigrescens.
AB  - Degradation of immunoglobulins is thought to be an important factor in the
      causation of periodontal diseases by hindering local host defenses and by
      providing nutrients to the periodontal microflora. In this study, we
      characterized the proteolytic activity against human immunoglobulin G (IgG) of 20
      strains of Prevotella intermedia and Prevotella nigrescens isolated from
      periodontal pockets and oral abscesses. IgG degradation was studied by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis. All strains degraded IgG
      within 48 h after growth in trypticase-yeast extract medium (TY) supplemented
      with 0.3% IgG. Incorporating IgG in TY broth enhanced bacterial growth. Protease
      profiles (zymography), which revealed the presence of 1-4 IgG-degrading
      proteolytic bands in bacterial cell extracts, became more complex after growth in
      the presence of IgG. A 38-kDa protease capable of degrading IgG nonspecifically
      was present in almost all strains. The proteolytic activity was mainly located on
      the surface of the cell envelope. Two strains of P. intermedia and P. nigrescens
      ATCC 33563 were selected for further studies. Bacterial cell suspensions in
      phosphate-buffered saline completely degraded human IgG, IgA and IgM within 24 h.
      This activity depended on reducing conditions and was inhibited at temperatures
      above 50 degrees C. The pH optimum of immunoglobulin degradation was at pH 7.
      Strains cultured at 42 degrees C showed a markedly reduced capacity to degrade
      IgG. Inhibition studies revealed that breakdown of IgG was caused by a cysteine
      protease(s). The capacity of P. intermedia and P. nigrescens to degrade
      immunoglobulins may explain their association with polymicrobial oral diseases.

PMID- 7567061
TI  - Patterns of antibody response in subjects with periodontitis.
AB  - Periodontal diseases comprise a heterogeneous group of infections that are
      difficult to distinguish on a clinical basis alone. The purpose of the present
      investigation was to group periodontitis subjects according to their elevated
      serum antibody levels to specific subgingival species. A total of 119 subjects
      (19-70 years) with evidence of prior periodontal destruction were monitored at 2
      month intervals (maximum 8 visits), prior to therapy, using clinical parameters
      measured at 6 sites per tooth. The probing attachment level was measured twice at
      each visit, and an increase of > 2.5mm at a site was used to define subjects with
      progressing disease. Serum samples were obtained from each subject at each visit
      and the level of antibody determined by enzyme-linked immunosorbent assay to 12
      subgingival species. Subgingival plaque samples were taken from the mesial aspect
      of all teeth in each subject at each visit, and the levels of 14 different
      subgingival species were determined using a colony-lift method and DNA probes.
      Subjects were grouped by cluster analysis of their elevated antibody levels using
      a simple matching coefficient. Ninety-two subjects fell into 9 clusters with 100%
      similarity; 29 subjects in one cluster group exhibited elevated antibody to none
      of the test species. Seven subjects in a second cluster group showed elevated
      antibody to Bacteroides forsythus. Subjects in the other 7 clusters showed
      elevated antibody to Actinobacillus actinomycetemcomitans serotype a only or in
      combination with B. forsythus, A. actinomycetemcomitans serotype b, Prevotella
      intermedia or Porphyromonas gingivalis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567063
TI  - Identification of linear antigenic sites on the Porphyromonas gingivalis 43-kDa
      fimbrillin subunit.
AB  - The fimbrillin of Porphyromonas gingivalis is thought to be an important
      virulence factor that mediates adherence to host surfaces. The linear immunogenic
      and antigenic structure of P. gingivalis fimbrillin was investigated with
      synthetic peptides corresponding to the amino acid sequence predicted from the
      cloned fimbrillin gene for P. gingivalis 2561. A series of continuous and
      overlapping peptides corresponding to the entire sequence of P. gingivalis
      fimbrillin was used to immunize Wistar rats. The resulting polyclonal antibodies
      were used to test the antigenicity of the 43-kDa fimbrillin protein by enzyme
      linked immunosorbent assay and Western blot analysis. All the peptides elicited
      specific antibodies directed to the corresponding peptides but differed in their
      ability to elicit antisera that cross-reacted with either native or denatured
      fimbrillin. Antisera to various C-terminal one-third peptides were more reactive
      to the denatured monomeric form of fimbrillin by Western blot analysis. Antisera
      to peptide 99-110 was by far the most reactive against the native form of the
      oligomeric fimbrillin as well as the partially denatured oligomeric form of
      fimbrillin. The results indicate that amino acid residues 99-110 on the native
      fimbrillin protein are accessible to antibody binding and that the immunogen 99
      110, when conjugated to thyroglobulin, is able to mimic an epitope on the 43-kDa
      fimbrillin.

PMID- 7567065
TI  - Patterns and rates of growth of microcosm dental plaque biofilms.
AB  - Rates of growth in wet weight and changes in them over time were established for
      microcosm dental plaques cultured from the mixed salivary bacteria in an
      artificial mouth. Standardized conditions included a continuous supply of medium
      containing 0.25% mucin and 1.5 ml of 5% w/v sucrose in 6 min every 8 h. Plaques
      were weighed daily. Plaque wet weight and total protein were highly correlated.
      Plaque doubling times were 3-7 h over day 1 and 9-21 h over day 2, which is
      similar to in vivo plaques. Subsequently, growth curves were either linear or
      between a linear and exponential increase. Evidence was obtained for plaque
      blooms. Methyl paraben (0.2%) applied for 15 min (3.75 ml) 6 times daily
      inhibited growth but only for 3 days, after which the rate was similar to control
      plaques, indicating that selection for resistance had occurred. It was concluded
      that the regulation of plaque growth rates is complex and does not conform to
      simple growth pattern models. Detailed studies of plaque growth and the effects
      of antiplaque agents can be carried out using this experimental system.

PMID- 7567064
TI  - Molecular and immunological characterization of a 64-kDa protein of
      Actinobacillus actinomycetemcomitans.
AB  - The 64-kDa protein to which about half the sera from patients with localized
      juvenile periodontitis and rapidly progressive periodontitis reacted strongly was
      purified from Actinobacillus actinomycetemcomitans Y4. Determination of the N
      terminal sequence of the protein revealed that it was a GroEL-like protein. The
      DNA fragment containing the groEL gene of A. actinomycetemcomitans was amplified
      by polymerase chain reaction, and the groESL operon was cloned by using colony
      hybridization with the amplified fragment from A. actinomycetemcomitans
      chromosomal DNA. Sequence analysis revealed that structures of the operon and its
      products were typical in gram-negative bacteria. Rabbit polyclonal antibodies to
      the 64-kDa protein cross-reacted with approximately 65-kDa proteins of
      Haemophilus aphrophilus, Haemophilus influenzae, Haemophilus paraphrophilus,
      Escherichia coli and Eikenella corrodens but not with any cellular proteins of
      Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum. It
      is possible that antibodies reactive to the 64-kDa protein in periodontitis
      patients are induced by the cross-reactivity with the hsp60 proteins of other
      bacteria.

PMID- 7567066
TI  - Colonization of the oral cavity of mice by an unidentified streptococcus.
AB  - While studying the oral bacterial biota of mice, we observed an unidentified
      streptococcus (TG) that eventually became the dominant species of the oral
      cavities of all other mice in our animal facility. We found that the strain is
      indigenous to Jackson Laboratory mice but is absent in animals from Charles River
      Laboratories. TG was also transmitted from artificially contaminated BALB/c mice
      to the oral cavities of 4 other mouse strains. Streptococcus sp. TG stimulated
      the secretory and systemic immune systems of artificially contaminated Charles
      River BALB/c mice but did not provoke clinical symptoms. The increase in antibody
      level to TG did not prevent its colonization and persistence in these mice. In
      mice from Jackson Laboratory, the secretory and systemic immune response to TG
      was significantly lower. In vitro, Streptococcus sp. TG inhibited murine oral
      lactobacilli and staphylococci, probably due to the production of hydrogen
      peroxide.

PMID- 7567067
TI  - Sucrose-dependent accumulation of oral streptococci and their adhesion-defective
      mutants on saliva-coated hydroxyapatite.
AB  - The adhesion and accumulation of oral streptococci on saliva-coated
      hydroxyapatite was examined in strains representing species that appear in
      initial plaque (Streptococcus sanguise FC1 and Streptococcus oralis C5) and in
      more mature plaque (Streptococcus gordonii G9B). Washed cells of strains FC1 and
      C5 did not attach better to saliva-coated hydroxyapatite than did strain G9B,
      suggesting that the degree of initial adhesiveness does not alone account for the
      temporal appearance of these bacteria in dental plaque. Growing cells of each
      strain were also examined for their ability to accumulate on saliva-coated
      hydroxyapatite. The addition of sucrose to the medium promoted the accumulation
      of strain G9B more than it promoted the accumulation of strains FC1 and C5.
      Sucrose also enhanced the accumulation of adhesion-defective mutants of each
      strain to levels similar to those of the respective parent strains. These results
      suggest that sucrose-dependent accumulation may facilitate the colonization of
      the tooth surface by these species of oral streptococci when adhesion is limited
      by reduced bacterial adhesiveness or limited pellicle-binding sites.

PMID- 7567068
TI  - Characterization of glutamine transport in Streptococcus mutans.
AB  - Glutamine transport in glucose-energized cells of Streptococcus mutans Ingbritt
      exhibited Michaelis-Menten-type kinetics with a Vmax of 13.4 nmol/mg dry
      weight/min and a Kt of 4.1 microM. Diffusion of glutamine into de-energized cells
      of S. mutans displayed similar type kinetics, with a Kt of 6.8 microM but with a
      markedly reduced Vmax of 53.9 pmol/mg dry weight/min. Glutamine transport in S.
      mutans is not proton motive force-driven, as the intracellular accumulation of
      glutamine by energized cells far exceeded the thermodynamic limits of the proton
      motive force, and the dissipation of this proton motive force by gramicidin in a
      high K+ medium did not decrease the intracellular glutamine concentration.
      Glutamine transport is therefore likely to be energized by ATP hydrolysis. The
      activity of the transporter was maximal between pH 6.0 and 7.0 and decreased
      rapidly above pH 7.0. The transport of glutamine was not competitively inhibited
      by asparagine, glutamate or aspartate, indicating a specific glutamine transport
      system. Reversed-phase high-pressure liquid chromatography of cell extracts
      revealed that approximately 26% of the glutamine taken into the cell was
      converted to glutamate within 10 min. The results are consistent with transported
      glutamine being converted to glutamate and ammonia by the action of an
      intracellular glutaminase. Glutamine therefore may be an important source of
      nitrogen for the cell.

PMID- 7567069
TI  - Primer extension analysis of Streptococcus mutans promoter structures.
AB  - To characterize the promoter structures of Streptococcus mutans genes, primer
      extension analysis was carried out with 4 genes previously isolated in this
      laboratory. An analysis of the transcription start sites for the gtfB, gtfC, gtfD
      and ftf genes revealed that each transcript was initiated at a purine residue.
      Based on these sites, the -10 and -35 sequences for each transcript were deduced
      and compared. For all 4 transcripts, the -10, but not the -35, sequences were
      homologous to the Escherichia coli promoter consensus sequences.

PMID- 7567071
TI  - [The dynamics of the species composition of nidiculous animals in different types
      of nests of the little suslik].

PMID- 7567070
TI  - [The biorhythmology of primary and superinvasive opisthorchiasis. Seasonal
      changes in the circadian dynamics of the peripheral blood composition in golden
      hamsters].
AB  - 540 golden hamsters were selected into 3 groups: 1--free from invasion, 2--once
      infected, 3--repeatedly infected with Opisthorchis felineus. Diurnal activity of
      peripheral blood composition was investigated in spring, autumn and winter at 3,
      7, 11 a.m. and 3, 7, 11 p.m. The dependence of biorhythmical organisation of
      peripheral blood cell composition upon seasons and the opisthorchis invasion
      frequency was recovered. The eosinophilia is the marker reaction of
      opisthorchiasis acute phase and it depend upon the invasion frequency. Seasons
      and invasion frequency affect on all diurnal rhythm components (mezor, acrophase,
      amplitude) with most largest drift in spring.

PMID- 7567073
TI  - [The photoperiodic regulation of the development and diapause of the nymphs of
      the taiga tick Ixodes persulcatus (Ixodidae)].
AB  - Development and diapause in nymphs of Ixodes persulcatus at the age of 12 months
      are regulated at 18 degrees C by day-length according to the long-day
      photoperiodic reaction, and regimens of engorged nymphs are of main importance.
      Long-day photoperiods (LD 20:4) have stimulated non-diapause development in 97
      100% specimens (moulting of 50% nymphs in 67-69 days after feeding), but short
      day photoperiods (LD 12:12) have induced diapause (a delay of development over
      than 6 months) in 75% specimens.

PMID- 7567072
TI  - [The mass development of biting midges (Diptera: Ceratopogonidae) on the littoral
      of the White Sea].
AB  - The biting midges larvae fauna of the intertidal and supralittoral zones in
      Sel'dianaia small bay (Kandalaksha Bay of the White Sea) is studied. It is
      represented by Stilobezzia sp., Dasyhelea sp. and Culicoides manchuriensis
      immature stages. Their distribution displays the strict vertical zonation. The
      abundance of larvae collected differs strongly at the places with different
      conditions. The mass breeding of Culicoides and Dasyhelea in the tidal zone of
      Arctic Seas is noticed for the first time. The maximum density of larvae in
      several times greater compared to the similar biotopes of subtropical and the
      south of temporal regions.

PMID- 7567074
TI  - [The correlation of light and hygrothermal factors in the determination of the
      morphogenetic diapause of the larvae and nymphs of the taiga tick in the
      northwestern spurs of the eastern Sayan].
AB  - In the taiga of the region in question at the latitude 56 degrees N the
      photoperiod regimens of 25 June and 21 July determine 50% diapause in engorged
      larvae and nymphs of Ixodes persulcatus. The durations of the day time on these
      dates are 17 h 34 min and 16 h 45 min respectively. Seasonal fluctuations of
      temperature and precipitation in May-June are the main reasons for the
      modification of the critical photoperiod. In some years the critical dates for
      larvae and nymphs vary under these factors within the limits 11-28 July and 19
      June-6 July respectively. The critical durations of the day time for these date
      limits are 16 h 20 min-17 h 12 min and 17 h 23 min-17 h 37 min respectively.

PMID- 7567075
TI  - [The probable utilization of the protective properties of the vector's saliva by
      the causative agents of specifically tick-borne infections].
AB  - It is proved that in the tick fluid saliva and in the cement plug produced by
      Rhipicephalus appendiculatus there are bactericidal substances very similar in
      their activity to the egg lysozyme. The possible role in the transmission and
      conservation of the specific tick-borne, insensitive to the lysozyme pathogens
      such as rickettsiae, tick-borne encephalitides virus and borreliae (pathogen of
      Lyme disease) is discussed. It is supposed, that bactericidal substances in the
      cement plug protect accumulated in it the tick-borne pathogens (TBE virus,
      borreliae) from the compete and destructive influence of the vulgar, mainly
      coccal microflora and from the purulent inflammation, which hinders not only tick
      feeding but probably specific tick-borne pathogens spreading in the vertebrate
      host.

PMID- 7567076
TI  - [The mathematical modelling of tropical malaria].
AB  - The new mathematical model of P. falciparum malaria has been created. One means
      the operational forecast of epidemic process when different control measures are
      realized. The original modelling methodology for epidemics is used. The proposed
      methodology is allowed to take into account the natural variety of model's
      parameters. The malaria model consists of the nonlinear integro-differential in
      partial derivatives combined equations including individual and population
      characteristics. The informatics technologies permits to see information about
      model and its grounds. The model's verification has been done on data of Garki
      project.

PMID- 7567077
TI  - [The taxonomic status of cestodes with an unusual localization from Antarctic
      seals].
AB  - The great structural diversity in the cestodes Glandicephalus antarticus (Baird,
      1853) from the stomach and intestine of the Ross Seal and G. perfoliatus
      (Railliet et Henry, 1912) from the bile-pancreatic duct of the Weddel Seal was
      recovered. These two cestodes are moved out of the family Diphyllobothriidae
      Luhe, 1910 and considered as the new family Glandocephalidae fam. n. within the
      superfamily Diphyllobothrioidea. Redescriptions of both species, and some indices
      of invasion rate are provided.

PMID- 7567078
TI  - [The biorhythmology of primary and superinvasive opisthorchiasis. The seasonal
      changes in the circadian activity of the portal (regional) lymph node in golden
      hamsters].
AB  - 540 male golden hamsters were divided into 3 groups: I--free from invasion, II-
      once infected, III--repeatedly infected. Diurnal activity of portal lymph node
      immunocompetent cells was investigated in spring, autumn and winter at 3, 7, 11
      a. m. and 3, 7, 11 p. m Peculiarities of diurnal immunocompetent cell activity at
      on acute opisthorchiasis stage, depending upon a season invasion frequency is
      determined by immunoreactivity level. Eosinophilic and lymphocytic reactions and
      the ratio of mitotic activity to degenerative elements are the lymph-node
      immunocompetence indices.

PMID- 7567079
TI  - [Cryptosporidium parvum (Apicomplexa: Sporozoa, Coccidia)--the optimization of a
      technic for isolating a large number of oocysts].
AB  - The Waldman e. a. (1986) method of separation of Cryptosporidium spp. oocysts
      from feces by using a percoll discontinuous density gradient appeared a method of
      choice for obtaining large numbers of oocysts of C. parvum free of fecal
      contamination. Feces of 7-12 day old calves, spontaneously infected with C.
      parvum, were concentrated and purified by the above technique. The purified
      oocysts were shown to be infectious by inoculation of 6-9 day old rats with an
      average dose of 20,000 oocysts per animal. The rats shed oocysts after 4 days. At
      necropsy on day 4 postinoculation, the pattern of endogenous development appeared
      normal, when examined on frozen sections of fresh tissue, using the Bright
      cryostat, stained with hematoxylin and eosin. Samples of the clean sediment,
      presumably containing only oocysts of C. parvum, were smeared and stained with
      carbol fuchsin after Ziehl-Neelsen, and with gentian violet after Sidorenko
      (1988). With the latter technique, an intense gentian violet staining screened
      all the constituents of the smear, except the oocysts, which being "negatively
      stained" looked as small transparent spheres 4-5 mkm in diameter. But of special
      interest was the reaction of the smeared organisms with carbol fuchsin. Some
      organisms stained dark red and had a variable number of dark granules, seemingly
      on the surface; whereas others stained light reddish, if at all, and appeared as
      transparent spheres. It does not seem unlikely that the sediment, resulting from
      the final step of percoll separation, may contain, besides oocysts, some other
      endogenous stages (meronts, gamonts, thin-walled oocysts) that appeared in the
      lumen of the intestine because of an intense flow of diarrheal fluid during
      cryptosporidiosis. Unlike the thick walled oocysts, other endogenous stages are
      not covered with protective walls and thus fail to absorb acid fast staining.
      Segmented meronts were obviously observed on the rat fecal smears 96 hours after
      infection. This observation enables us to propose that newly infected hosts
      recipients may obtain, with diarrheal fecal masses of infected donors, not only
      sporulated oocysts, but also some earlier developmental stages. Merozoites,
      released from the segmented meronts, could start in the intestine asexual rounds,
      thus shortening the resulting prepatent period. Fluctuations in prepatent period
      duration are characteristic of Cryptosporidium spp., and the above observation
      may be one of its explanations.

PMID- 7567081
TI  - Models of care using unlicensed assistive personnel. Part I: Job scope,
      preparation and utilization patterns.
AB  - This article describes the results of a NAON-funded descriptive design research
      project developed to gather data on how clinical nursing assistants are being
      used in the practice setting by examining the role responsibilities, extent of
      delegation, training effectiveness, and evaluation measures designed by agencies
      to evaluate the effectiveness of this model of care. Fifty-three hospitals from
      31 states participated in the investigation, with 53 nurses managers, 620 staff
      nurses, and 305 nursing assistants responding to questionnaires. The most common
      role description of clinical nursing assistants was in providing supportive care;
      however, there was a clear trend toward using clinical assistants to provide care
      requiring higher levels of observation and technical skill. Deficiencies in the
      infrastructure to support this model were identified as limited education and
      training of both assistants and staff nurses, inadequate mechanisms to deal with
      role confusion and delegation deficits, lack of evaluation systems, and lack of
      ongoing procedures to assure competency.

PMID- 7567080
TI  - [Blastocystis fauna].
AB  - On the area of former USSR and Russia 10 species of Blastocystis were described:
      Blastocystis lessonae from Rana lessonae, B. anatis from Anas platyrhynchos, B.
      anseri from Anser anser, B. galli from Gallus gallus, B. numidae from Numida
      meleagris, B. meleagridis from Meleagris gallopavo, B. equi from Equus coballus,
      B. suis from Sus scrofa, B. bovis from Bos taurus, B. ovis from Ovis aries.

PMID- 7567082
TI  - Blount disease (idiopathic tibia vara).
AB  - Blount disease or idiopathic tibia vara is a developmental deformity of the
      proximal tibial medial physis that produces a varus deformity of the knee. It is
      classified by early or late onset. The etiology is not entirely clear but is
      presumed to be related to an abnormal compression on the medial aspect of the
      proximal tibial physis. Early diagnosis is important for a better prognosis. In
      general, the later the onset and the greater the progression of the deformity,
      the increased likelihood of articular changes. Orthotics are recommended as the
      first type of treatment. If progression occurs or onset is late, surgical
      intervention may be warranted. The nurse's role ranges from educating the family
      about the disease to helping them adapt to the varying treatments.

PMID- 7567083
TI  - Development of the practice guidelines for acute low back problems in adults.

PMID- 7567084
TI  - Management of the patient with complex orthopaedic fractures.
AB  - Patients who sustain complex orthopaedic fractures related to a traumatic event
      can develop devastating complications. Patients who sustain open fractures are at
      greater risk for complications such as wound and systemic infections and nonunion
      of the fracture itself. This article describes the management of open complex
      extremity fractures through a case study approach.

PMID- 7567085
TI  - The legislative process.
AB  - These are years of rapid change in health care. Nurses face many challenges and
      have many opportunities to participate in and influence the formation of health
      care policy. Nurse citizens can become very effective in their lobbying efforts,
      whether on the federal, state, or local level, when they are armed with
      information about the key players and the processes and their belief in what
      nursing can contribute to the health care system.

PMID- 7567086
TI  - Chinese foot binding.
AB  - Chinese foot binding embraced several modern principles of brace treatment. It
      was initiated in childhood while the foot was cartilaginous and moldable.
      Culturally, the practice attempted to shape the foot into a pointed lotus flower.
      The resultant cavus foot deformity was dysfunctional and crippling. This curious
      custom, outlawed by the Communist party, is ironically analogous in some ways to
      high-heel shoe wear.

PMID- 7567087
TI  - Local application of antibiotics in orthopaedic infections.
AB  - Local administration of high doses of antibiotics may be done with the use of
      antibiotic beads. The advantages of this treatment modality would seem to
      outweigh the disadvantages.

PMID- 7567088
TI  - Competing in the new job market. Part 2: The interview.

PMID- 7567089
TI  - Reimbursement for NPs and CNSs is introduced in house and senate.

PMID- 7567090
TI  - Medicare-Medicaid restructuring debated by ANA House of Delegates.

PMID- 7567091
TI  - Marching together.

PMID- 7567092
TI  - Skeletal and cutaneous sequelae to meningococcal purpura.
AB  - Meningococcal infection can produce symptoms that have severe morbid or even
      fatal effects. The survival rate has increased over the last 20 years and health
      care workers are now faced with managing the sequelae of cutaneous and skeletal
      necroses. It is important for nurses to recognize symptoms of the disease as well
      as associated complications. A multidisciplinary approach is needed to manage all
      phases of the illness. This phenomenon occurs most commonly in children but may
      be seen in adolescents and young adults as well. Despite extensive alteration in
      body image and the need for long-term rehabilitation, with proper management, a
      full recovery may be expected.

PMID- 7567093
TI  - Parasites of wild brown rats (Rattus norvegicus) on UK farms.
AB  - Wild brown rats (Rattus norvegicus) from 11 rural UK farmsteads were found to
      carry 13 zoonotic and 10 non-zoonotic parasitic species, many of which (e.g.
      Cryptosporidium, Pasteurella, Listeria, Yersinia, Coxiella and Hantavirus) have
      rarely or never been previously investigated for wild rats. The study suggests
      that wild brown rats, serving as vectors of disease, represent a serious risk to
      the health of humans and domestic animals in the UK.

PMID- 7567095
TI  - Plasticity of gp63 gene organization in Leishmania (Viannia) braziliensis and
      Leishmania (Viannia) peruviana.
AB  - The genomic organization of gp63 genes in 4 and 7 isolates of Leishmania
      braziliensis and L. peruviana, respectively was studied by RFLP analysis with 3
      restriction enzymes (Bgl I, Sal I and Apa I). Our results showed a marked
      polymorphism among isolates. Some characters were specific to L. braziliensis or
      to L. peruviana, and others specific to the respective biogeographical
      populations of L. peruviana. The average minimum copy number of gp63 genes was
      found to be higher in L. braziliensis (71) than in L. peruviana (46), suggesting
      that deletion of gp63 genes might be partially involved in the size decrease of
      the chromosome bearing gp63 genes, observed between those 2 species (from 700 to
      610 kb). Our results may suggest the existence of at least 2 arrays of
      heterologous gp63 repeats, varying in relative copy number between L.
      braziliensis and L. peruviana, and among isolates of the latter species.
      Rearrangement of the gp63 genes was observed during long-term in vitro
      maintenance of a reference strain of L. braziliensis. These observations document
      the existence of a dynamic gp63 gene organization in Leishmania of the
      braziliensis complex.

PMID- 7567094
TI  - Decreased predator avoidance in parasitized mice: neuromodulatory correlates.
AB  - Although parasites are reported to alter host responses to predators, little is
      known about the neurochemical mechanisms involved. Using an odour preference
      test, we examined the effects of an acute, subclinical infection with the
      naturally occurring, single host, enteric protozoan parasite, Eimeria
      vermiformis, on the responses of male laboratory mice, Mus musculus, to a
      predator. Uninfected mice avoided the odour of a predatory cat, spending a
      minimal amount of time in a Y-maze in the vicinity of the cat odour. In contrast,
      mice infected with E. vermiformis, spent a significantly greater amount of time
      in the proximity of the cat odour, showing a reduced avoidance of the cat odour
      and a reduction in predator-induced fear or anxiety. This was not related to
      augmented opioid activity and decreased pain sensitivity in the infected mice, as
      neither treatment with the exogenous opiate, morphine, nor restraint stress
      induced augmentation of endogenous opioid activity, had any significant effects
      on the responses of uninfected mice to cat odour. The altered responses of the
      infected mice to the cat odour were reduced by peripheral administration of the
      gamma-aminobutyric A (GABAA) antagonists, bicuculline and picrotoxin, but were
      not significantly affected by either the benzodiazepine antagonist, Ro 15-1788,
      the opiate antagonist, naloxone, or the excitatory amino acid, N-methyl-D
      aspartate (NMDA) antagonist, MK-801. These results indicate that infection with
      E. vermiformis in mice reduces the avoidance of predator odour through
      neurochemical systems associated with anxiety involving, at least in part, GABAA
      receptor mechanisms.

PMID- 7567096
TI  - Changes in lipophosphoglycan and gene expression associated with the development
      of Leishmania major in Phlebotomus papatasi.
AB  - Stage-specific molecular and morphogenic markers were used to follow the kinetics
      of appearance, number, and position of metacyclic promastigotes developing during
      the course of L. major infection in a natural vector, Phlebotomus papatasi.
      Expression of surface lipophosphoglycan (LPG) on transformed promastigotes was
      delayed until the appearance of nectomonad forms on day 3, and continued to be
      abundantly expressed by all promastigotes thereafter. An epitope associate with
      arabinose substitution of LPG side-chain oligosaccharides, identified by its
      differential expression by metacyclics in vitro, was detected on the surface of a
      low proportion of midgut promastigotes beginning on day 5, and on up to 60% of
      promastigotes on days 10 and 15. In contrast 100% of the parasites egested from
      the mouthparts during forced feeding of 15 day infected flies stained strongly
      for this epitope. At each time-point, the surface expression of the modified LPG
      was restricted to morphologically distinguished metacyclic forms. Ultrastructural
      study of the metacyclic surface revealed an approximate 2-fold increase in the
      thickness of the surface coat compared to nectomonad forms, suggesting elongation
      of LPG as occurs during metacyclogenesis in vitro. A metacyclic-associated
      transcript (MAT-1), another marker identified by its differential expression in
      vitro, also showed selective expression by promastigotes in the fly, and was used
      in in situ hybridization studies to demonstrate the positioning of metacyclics in
      the anterior gut.

PMID- 7567097
TI  - Replication, differentiation, growth and the virulence of Trypanosoma brucei
      infections.
AB  - This study had 2 objectives: first, to investigate how the processes of slender
      form replication, of differentiation from dividing slender to non-dividing stumpy
      forms, and of stumpy mortality, combine to determine the initial (acute-phase)
      growth rate of Trypanosoma brucei populations; second, to determine how acute
      phase growth rates influence parasite densities during the subsequent, chronic
      phase of infection. During the acute phase, slender and stumpy populations both
      grew approximately exponentially, the latter more slowly than the former.
      Mathematical models showed how this difference in slender and stumpy growth rates
      can be explained in terms of heterogeneous replication and differentiation rates.
      Stumpy life-expectancy was determined for one stock and found to be age-dependent
      with a half-life of 48-72 h, much larger than observed population doubling times
      of 5-10 h. A comparison of cloned stocks showed that the highest parasite
      densities during the chronic phase were associated with the highest acute-phase
      growth rates of both the whole parasite population and of the subpopulation of
      slender forms. By contrast, high chronic-phase parasitaemias artificially
      produced following rapid syringe passage were associated with low acute-phase
      growth rates of slender forms. Syringe-passaging is a laboratory procedure which
      selects for virulent parasites, but these parasites behave differently from
      naturally virulent stocks.

PMID- 7567098
TI  - Molecular characterization of trypanosome species and subgroups within subgenus
      Nannomonas.
AB  - Restriction fragment length polymorphism (RFLP) analysis of both genomic and
      kinetoplast DNA from representative stocks from 3 Trypanosoma congolense
      subgroups (Savannah, Forest, and Kilifi), T. simiae and T. godfreyi, was used to
      investigate the relatedness of the different groups within subgenus Nannomonas.
      DNA probes for beta-tubulin and the ribosomal DNA (rDNA) locus were isolated from
      a T. congolense Savannah genomic library; additional probes were generated by PCR
      amplification of mini-exon and glutamate and alanine rich protein (GARP) gene
      sequences. Our results provide evidence that at the molecular level the T.
      congolense Savannah and Forest groups are the most closely related groups within
      the subgenus Nannomonas: the Savannah and the Forest groups had mini-exon gene
      repeats of identical size, which shared homology, had mini-circles of the same
      size and had a high level of similarity (63%) when the banding patterns produced
      with a tubulin and rDNA probe were subjected to numerical analysis. All other
      pairwise combinations of groups have very low percentage similarities of < 10%,
      suggesting that the Kilifi group trypanosomes, are as distantly related to the T.
      congolense Savannah and Forest groups as they are to T. simiae or T. godfreyi.
      The conservation of the GARP gene between the Savannah, Forest and Kilifi groups
      provides the only evidence linking the Kilifi trypanosomes to the other groups in
      T. congolense. We find no evidence for the presence of the GARP gene in the T.
      simiae or T. godfreyi group trypanosomes.

PMID- 7567099
TI  - Identification of a 44 kDa protein localized within the endoplasmic reticulum of
      Trypanosoma brucei brucei.
AB  - Immunoaffinity chromatography and gel electrophoresis were used to isolate a 44
      kDa protein that was bound to a 72 kDa chaperone in Trypanosoma brucei brucei. A
      polyclonal antiserum to the 44 kDa protein was raised in rats and employed in
      conjunction with chromatography using DEAE-cellulose, Sephacryl S-300, and
      hydroxyapatite to purify the protein from membranes of bloodstream forms of the
      trypanosomes. Immunoblot analysis using this antiserum revealed a protein doublet
      of 44/45 kDa in T. b. brucei and a single protein band of 53 kDa in almost
      equivalent amounts throughout the life-cycle stages of T. congolense. Indirect
      immunofluorescence using affinity-purified antibodies specific for the 44 kDa
      protein showed labelling of the perinuclear area and reticular system extending
      throughout the parasites, suggesting that this protein was located in the
      endoplasmic reticulum. Localization of the 44 kDa molecule in the endoplasmic
      reticulum was confirmed by immunoelectron microscopy. Protease protection
      experiments demonstrated that the epitopes bound by antibody were buried within
      the membrane or towards the lumenal face of the endoplasmic reticulum. Ruthenium
      Red overlay of nitrocellulose blots containing the 44/45 kDa doublet suggested
      that the molecules have the potential to bind calcium. The N-terminal amino acid
      sequence of the 44 kDa protein showed no sequence similarity to any proteins in
      the database.

PMID- 7567100
TI  - Glycans with N-acetyllactosamine type 2-like residues covering adult Schistosoma
      mansoni, and glycomimesis as a putative mechanism of immune evasion.
AB  - Glycans at the surface of adult Schistosoma mansoni were investigated with gold
      labelled lectins. The fragile complex of the glycans with the outer membranes
      could be preserved for electron microscopy by avoiding extensive pre-fixation
      with aldehydes and by introducing osmium-ferrocyanide as a membrane fixative.
      Male and female worms were entirely covered with glycans that intensely bound
      lectins from Erythrina cristagalli and Datura stramonium, suggesting that
      galactose(beta 1-4)N-acetylglucosamine residues occur in high numbers in the
      surface glycans. Similar staining was obtained with lectins from Triticum
      vulgaris, Glycine max and Ricinus communis agglutinin I, which react with N
      acetylglucosamine or terminal galactose residues and bind non-selectively with
      high affinity to N-acetyllactosamine. Fucose, N-acetylgalactose and sialic acid
      were not detected with lectins and sialidase treatment. The tegument contained an
      abundance of glycans with the same lectin reactivities as the surface-expressed
      molecules, indicating that the worms synthesize and replenish their surface
      glycans and do not merely adsorb host substances. Glycomimesis is discussed as a
      mechanism of immune evasion in view of N-acetyllactosamine being a common and
      weakly immunogenic component in glycans of vertebrate hosts. S. mansoni might
      disguise themselves with the glycans against attack by immune effectors.

PMID- 7567101
TI  - Susceptibility of brook charr, Salvelinus fontinalis to the pathogenic
      haemoflagellate, Cryptobia salmositica, and the inheritance of innate resistance
      by progenies of resistant fish.
AB  - Eighty-seven of 175 laboratory raised F1 generation brook charr (Salvelinus
      fontinalis) were resistant to experimental Cryptobia salmositica infection.
      Susceptibility to the pathogen was not related to age nor to route of infection.
      Plasma of resistant charr lysed the parasite under in vitro conditions while
      those of susceptible fish did not. Sperm from 4 susceptible and 4 resistant male
      charr, from 8 F1 families, were used to fertilize eggs from 2 hatchery raised
      susceptible charr. Susceptibility of progenies (F2 families) was determined 4
      weeks after inoculation of the parasite. All progenies (seven F2 families) of 4
      susceptible males were susceptible to experimental infection and their plasma did
      not lyse the parasite. It was presumed that these susceptible progenies were
      homozygous recessive (rr), and that the resistant allele was dominant. All
      progenies (two F2 families) of 1 resistant male (presumed RR) and 2 susceptible
      females were all resistant to infection and their plasma lysed the parasite. The
      ratio of resistant to susceptible charr in 6 other F2 families from the other 3
      resistant males (presumed Rr) and two susceptible females was about 1:1. The
      results suggest a single Mendelian locus which determines innate resistance to C.
      salmositica infection in brook charr and that it is possible to breed Cryptobia
      resistant fish.

PMID- 7567102
TI  - Investigation of the chemosensory function of amphids of Syngamus trachea using
      electrophysiological techniques.
AB  - Syngamus trachea, the gape nematode, has been used as a model to study the
      chemosensory function of amphids. Extracellular electrophysiological recordings
      were performed directly on amphids. The amphids were stimulated by blood serum
      from a host bird and by D-tryptophan. The spike frequency produced by the amphid
      increased significantly after the application of the serum and the application of
      D-tryptophan. Two types of amphidial neurones responded to the presence of the
      stimuli. These extracellular recordings have verified the chemosensory function
      of the amphids.

PMID- 7567103
TI  - Isolates of Trichuris muris vary in their ability to elicit protective immune
      responses to infection in mice.
AB  - Much of what is currently known of the host-parasite interaction between mice and
      the parasitic nematode Trichuris muris has come from experiments using a single
      parasite isolate (E/N). This isolate has been compared with 2 others which, on
      morphological criteria, belong to the same species. In 3 inbred strains of mouse
      that show distinct, genetically determined response phenotypes, there was a
      consistent pattern in terms of parasite survival time regardless of host strain,
      E/K worms being expelled early, E/N expelled later and S worms very late or not
      at all. High-responder CBA mice expelled E/K and E/N worms earlier than low
      responder C57 B1/10 mice. B10.BR mice were permissive to S isolate infection,
      mounted a very late response to E/N worms but expelled E/K worms effectively by
      day 25. The differential response of mice to these isolates provides an
      experimental system for identifying the basis of variation in this host-parasite
      relationship.

PMID- 7567104
TI  - The evolution of tissue migration by parasitic nematode larvae.
AB  - Migration by nematode larvae through the tissues of their mammalian hosts can
      cause considerable pathology, and yet the evolutionary factors responsible for
      this migratory behaviour are poorly understood. The behaviour is particularly
      paradoxical in genera such as Ascaris and Strongylus in which larvae undergo
      extensive migrations which begin and end in the same location. The orthodox
      explanation for this apparently pointless behaviour is that a tissue phase is a
      developmental requirement following the evolutionary loss of skin penetration or
      intermediate hosts. Yet tissue migration is not always necessary for development,
      and navigation and survival in an array of different habitats must require costly
      biochemical and morphological adaptations. Migrating larvae also risk becoming
      lost or killed by the host. Natural selection should therefore remove such
      behaviour unless there are compensating benefits. Here we propose that migration
      is a selectively advantageous life-history strategy. We show that taxa exploiting
      tissue habitats during development are, on average, bigger than their closest
      relatives that develop wholly in the gastrointestinal tract. Time to reproduction
      is the same, indicating that worms with a tissue phase during development grow
      faster. This previously unsuspected association between juvenile habitat and size
      is independent of any effects of adult habitat, life-cycle, or host size,
      generation time or diet. Because fecundity is intimately linked with size in
      nematodes, this provides an explanation for the maintenance of tissue migration
      by natural selection, analogous to the pre-spawning migrations of salmon.

PMID- 7567105
TI  - The action of serotonin and the nematode neuropeptide KSAYMRFamide on the
      pharyngeal muscle of the parasitic nematode, Ascaris suum.
AB  - The pharyngeal component of the enteric nervous system of the parasitic nematode,
      Ascaris suum exhibits immunoreactivity for serotonin (5-hydroxytryptamine or 5
      HT) and for FMRFamide-like peptides. This paper describes the application of an
      in vitro pharmacological approach to investigate the functional role of 5-HT and
      FMRFamide-like peptides. The pharyngeal pumping behaviour of Ascaris suum was
      monitored using a modified pressure transducer system which measures pharyngeal
      pressure changes and therefore pumping. The pharynx did not contract
      spontaneously; however, 5-HT (10-1000 microM) stimulated pumping at a frequency
      of 0.5 Hz. FMRFamide had no apparent effect on pharyngeal pumping. The native
      nematode FMRFamide-related peptide (FaRP), KSAYMRFamide inhibited the pumping
      elicited by 5-HT. The duration of inhibition was dose-dependent (0.1-1000 nM)
      with a threshold of 0.1 nM. In 4 preparations, the inhibition of the pharyngeal
      muscle was preceded by an initial excitation and increase in the amplitude of
      pharyngeal pressure changes. The pharynx is involved in various nematode
      processes, including feeding, regulation of hydrostatic pressure and excretion.
      The role of 5-HT and KSAYMRFamide in the pharyngeal function of nematodes is
      discussed.

PMID- 7567106
TI  - Antibody isotype responses to antigens of Ascaris lumbricoides in a case-control
      study of persistently heavily infected Bangladeshi children.
AB  - Antibody responses to Ascaris lumbricoides worm antigens were examined by ELISA
      in a case-control study of 2 groups of Bangladeshi children, one of which had
      been shown over a period of 12 months to be consistently lightly infected
      (controls) and the other consistently heavily infected (cases). The children
      showed a wide range in intensity of infection; children identified as cases were
      on average 4 times more heavily infected than the controls. There were no
      significant differences in weight, height, mid-upper arm circumference and
      skinfold thickness between the case or control subjects at the time blood samples
      for analyses by ELISA were collected. Children with repeatedly heavy infections
      with A. lumbricoides had higher concentrations of antibody isotypes to the
      antigens of A. lumbricoides than children who are repeatedly lightly infected.
      IgG1, IgG4 and IgE to worm antigens occurred in significantly higher
      concentrations in heavily infected subjects. This suggests that these antibody
      responses simply reflect the intensity of infection and may not play a
      significant role in protecting against heavy infections.

PMID- 7567107
TI  - The effect of two types of diet on populations of Ascaris suum and
      Oesophagostomum dentatum in experimentally infected pigs.
AB  - This investigation compared the effect of two common types of diet on worm
      burdens and faecal egg counts of pigs inoculated with Ascaris suum and
      Oesophagostomum dentatum. The diets were both considered nutritionally sufficient
      for pigs of this age, and gave high and comparable growth rates. Pigs were
      inoculated with both worm species at 14 weeks of age and slaughtered 3 or 12
      weeks later. At 3 weeks, A. suum larvae were numerous in the small intestine of
      pigs fed ground barley plus protein supplement, but were not detected from pigs
      fed a commercial full-constituent pelleted feed. At 12 weeks, however, average
      adult worm burdens were low and similar in both groups. At both slaughter times,
      O. dentatum worm burdens were significantly higher in pigs fed barley plus
      protein than in pigs given commercial feed, particularly for female worms, and
      the commercial diet led to worms being located further along the large intestine,
      and to reduced worm fecundity. The chemical composition of large intestinal
      contents differed significantly between pigs fed the two diets.

PMID- 7567108
TI  - [Evolution of the susceptibility to penicillin G of Streptococcus pneumoniae at
      the Limoge University Hospital Center].
AB  - A systematic detection of Streptococcus pneumoniae strains with reduced
      susceptibility to penicillin has been realized at Limoges Hospital during two
      years half. Of 302 strains isolated, 27 had reduced susceptibility to penicillin
      (8,9%), and, for 15 strains (5%), the MIC of penicillin G reached at least 2
      mg/l. The frequency of strains with reduced susceptibility to penicillin
      increased from 1992 to 1994: 8,2% in 1992, 8,7% in 1993 and 12,2% in 1994. The
      resistance level exhibited by pneumococcus strains increased since 1992: the
      percentage of resistant strains (MIC mg/l > 1) was 2,7% in 1992, 6,9% in 1993 and
      7,3% in 1994. Most of the strains with reduced susceptibility to penicillin
      belonged to serotype 23 (52%) and were isolated from blood cultures, cerebral
      spinal or pleural fluids (41%).

PMID- 7567110
TI  - [In vitro activity of six beta-lactams against 295 strains of enterobacteriaceae
      and P. aeruginosa isolated from neutropenic patients].
AB  - The in vitro activity of two new beta-lactam agents, cefpirome (CPO) and cefepime
      (FEP), was investigated against 295 Gram-negative bacilli (250 enterobacteriaceae
      and 45 P. aeruginosa) isolated from neutropenic patients. They were compared with
      ceftazidime (CAZ), piperacillin-tazobactam (TZP), imipenem (IPM) and cefotaxime
      (CTX). All enterobacteriacae were susceptible to IPM, 16 strains were
      intermediately susceptible or resistant to CAZ (1 strain of E. coli, 4 of
      Morganella morganii and 11 of Enterobacter. The 250 strains of enterobacteriacea
      were susceptible to FEP (MIC < 1 mg/l) and only one strain among them was
      intermediately susceptible to CPO. Among 45 strains of P. aeruginosa, 21 strains
      were susceptible to CPO, 30 to FEP, 31 to TZP, 32 to CAZ and 34 to IPM. All the
      strains were inhibited by less than 32 mg/l of FEP and IPM.

PMID- 7567109
TI  - [Bactericidal activity of combinations of ticarcillin-clavulanic acid or other
      beta-lactams (amoxicillin, piperacillin-tazobactam, ticarcillin) with gentamicin
      against Enterococcus faecalis and E. faecium].
AB  - MICs of amoxicillin, piperacillin-tazobactam, ticarcillin and ticarcillin
      clavulanic acid were determined against 52 clinical strains of E. faecalis and E.
      faecium. Modal MICs (mg/l) of these antibiotics were 1, 4, 64 and 64,
      respectively. Bactericidal activity of the beta-lactams was tested at two
      concentrations (1/2 MIC and 100 mg/l) alone or combined with gentamicin (4 mg/l)
      against 10 clinical strains of Enterococcus spp. Activity of ticarcillin was not
      modified by the addition of clavulanic acid (4 mg/l). Time-kill curves showed
      that all beta-lactams at 100 mg/l were bactericidal after 18 h of incubation
      (decrease in bacterial counts > or = 3 log10 CFU/ml) against 6 strains of E.
      faecalis, with MICs of amoxicillin at 1 mg/l and 2 strains of E. faecium with
      MICs of amoxicillin at 1 and 2 mg/l. Addition of gentamicin resulted in a
      bactericidal effect at 3 or 6 hours for the great majority of the combinations
      studied, except against the two strains highly resistant to gentamicin.
      Combination of every beta-lactam at 1/2 MIC with gentamicin was synergistic
      (except in case of high level resistance to gentamicin) and prevented bacterial
      growth but was not bactericidal. Against two strains of E. faecium with high MICs
      of amoxicillin (8 mg/l), piperacillin-tazobactam (64 mg/l) and ticarcillin
      clavulanic acid (512 mg/l), only combinations of amoxicillin 100 mg/l and
      gentamicin were always bactericidal. In conclusion, against E. faecalis strains,
      ticarcillin-clavulanic acid tested at 100 micrograms/ml had a bactericidal
      activity similar to that of the other beta-lactams tested, alone or combined with
      gentamicin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567111
TI  - [Comparative susceptibility of Ochrobactrum anthropi, Agrobacterium tumefaciens,
      Alcaligenes faecalis, Alcaligenes denitrificans subsp. denitrificans, Alcaligenes
      denitrificans subsp. xylosidans and Bordetella bronchiseptica against 35
      antibiotics including 17 beta-lactams].
AB  - Ochrobactrum anthropi, formerly known as "Achromobacter sp." or CDC group Vd has
      been isolated from water, hospital environment (antiseptic solutions, dialysis
      fluids ... ). O. anthropi is a Gram negative, motile, strictly aerobic, oxydase
      positive and non-fermentative bacteria with a strong urease activity. The
      susceptibility of 13 strains of O. anthropi was determined by agar diffusion
      method and compared to those of type strains of Agrobacterium tumefaciens,
      Alcaligenes faecalis, Alcaligenes denitrificans subsp. denitrificans, Alcaligenes
      denitrificans subsp. xylosoxydans and Bordetella bronchiseptica. The MICs of 20
      antimicrobial agents confirmed the distinct phenotype susceptibility of O.
      anthropi. All the strains of O. anthropi are sensitive to imipenem, amikacin,
      gentamicin, netilmicin, nalidixic acid, pefloxacin, ciprofloxacin, tetracyclin,
      colistin, sulphonamides and rifampicin and resistant to ampicillin, amoxycillin +
      clavulanic acid, ticarcillin, mezlocillin, cefuroxime, cefamandol, cefoxitin,
      cefotaxime, cefoperazon, ceftazidime, cefsulodin, aztreonam, streptomycin,
      kanamycin, pipemidic acid, chloramphenicol, erythromicin, pristinamycin,
      trimethoprim and fosfomycin. O. anthropi is implicated in nosocomial infections.
      O. anthropi was the species with the greatest resistance to beta-lactamins.

PMID- 7567112
TI  - [Bactericidal activity of 6 antibiotics and 3 combinations against 6 strains of
      Salmonella isolated from blood].
AB  - The bactericidal activity of 6 antibiotics and 3 combinations was evaluated
      against 6 Salmonella strains isolated from blood: 3 sensitive to all antibiotics
      tested (1 Salmonella Typhi, 1 Salmonella Paratyphi A et 1 Salmonella Enteritidis)
      and 3 harbouring a TEM penicillinase (1 Salmonella Typhi, 1 Salmonella Virchow et
      1 Salmonella Typhimurium). MICs of 6 antibiotics, ceftriaxone, cefotaxime,
      cefoperazone, ciprofloxacin, amikacin and chloramphenicol were determined by
      microdilution method in Mueller Hinton broth. The bactericidal activity of these
      antibiotics and 3 combinations (ciprocloxacin + ceftriaxone, ciprofloxacin +
      amikacin and ceftriaxone + amikacin) was determined by the killing curve method
      with 10(6) cfu/ml inocula and 4 x MIC for antibiotics concentrations.
      Chloramphenicol, only tested on typho-paratyphi strains, had only a
      bacteriostatic effect at 24 hours. Amikacin and ciprofloxacin had a faster and
      better bactericidal activity than cephalosporins. Combinations were either
      additive or synergistic. Those including amikacin had the best results, but any
      can be proposed for initial treatment of severe Salmonella infections in
      immunosuppressed patients.

PMID- 7567114
TI  - [In vitro antibacterial activity of a new fluoroquinolone, enoxacin against
      hospital bacteria and regression curve].
AB  - Minimal inhibitory concentrations (MICs) of enoxacin (ENX), a new fluoroquinolone
      indicated for the treatment of urinary tract infections, was determined by agar
      dilution for 703 bacterial strains isolated in 1993 in 3 university hospitals in
      order to study its activity against urinary pathogens; in addition, antibiograms
      by agar diffusion were performed with 5 micrograms disks to calculate the
      regression curve and the breakpoints for sensitivity testing. Activity of ENX
      against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that
      of other fluoroquinolones (FQ) (MIC 50 and 90: 0.25-0.5 microgram/ml); like for
      other FQ, this activity was reduced against NAL intermediate and resistant (R)
      Enterobacteriaceae (8-64) MICs of ENX against P. aeruginosa were between 0.5 and
      128 (2- > 128). ENX had also a good activity against NAL-S A. baumannii (0.06-2)
      but this activity is reduced against NAL-R Acinetobacter (0.5- > 128). ENX showed
      activity close to the currently available FQ against methicillin susceptible
      Staphylococci (0.5-8); the resistant strains (32- > 64) are usually methicillin
      resistant. ENX is less effective against Enterococci (4-128). The coefficient
      correlation of the regression curve is 0.906. For MIC breakpoints of 1 and 2
      micrograms/ml, zone diameter breakpoints should be 22 and 19 mm.

PMID- 7567113
TI  - [Susceptibility to quinolones of Salmonella isolated from men and animals].
AB  - Fluoroquinolones are efficacious antibiotics for the treatment of Salmonella
      infections in humans. One of these quinolones, enrofloxacin, a precursor of
      ciprofloxacin, is used to treat respiratory infections in calves and poultry.
      There is a risk of developing resistant strains of Salmonella in animals, which
      may then contaminate humans. To evaluate current susceptibilities of Salmonella
      strains to quinolones, we collected 95 strains belonging to various serotypes in
      a district of intensive breeding (the Ille-et-Vilaine Departement): 54 human
      strains, 24 bovine strains, and 17 poultry strains. The technique of dilutions in
      agar medium was used to determine Minimal Inhibitory Concentrations (MICs) for
      the following antibiotics: nalidixic acid, norfloxacin, pefloxacin, ofloxacin,
      ciprofloxacin, levofloxacin and clinafloxacin. Our results showed that human
      Salmonella strains remained very susceptible to quinolones. Only 3 animal strains
      had nalidixic-acid MICs > 128 mg/l. For these 3 strains, pefloxacin and
      ciprofloxacin MICs were respectively 1 or 2 mg/l and 0.25 mg/l. For all the other
      human and animal strains the nalidixic-acid MICs were < 4 mg/l, and their MICs 90
      were: 0.12 mg/l for ofloxacin and norfloxacin, 0.06 mg/l for pefloxacin, 0.03
      mg/l for ciprofloxacin, 0.016 mg/l for levofloxacin, and 0.004 mg/l for
      clinafloxacin.

PMID- 7567115
TI  - [Comparative activity of azithromycin against 100 strains of Neisseria
      gonorrhoeae].
AB  - Azithromycin is a new semisynthetic, acid stable C15 macrolid. In our study, we
      compared in vitro activity of azithromycin with 6 other antibiotics usually
      recommended for treatment of N. gonorrhoeae infections: erythromycin, ampicillin,
      amoxicillin, ceftriaxone, spectinomycin, ciprofloxacin. 100 strains have been
      selected: 95 clinical strains with different resistance patterns: 60 susceptible
      to beta-lactams, 25 PPNG, 10 chromosomal decreased susceptibility to beta
      lactams. Among these strains, 13 had a decreased susceptibility to erythromycin
      (MIC: 2 and 4 mg/l) and 5 WHO reference strains: A: spectinomycin resistance, B:
      wild phenotype, C: chromosomal decreased susceptibility to penicillin and
      tetracycline, D: chromosomal resistance to penicillin and
      erythromycin+chromosomal decreased susceptibility to chloramphenicol, E: beta
      lactamase producing strain (PPNG) and decreased susceptibility to tetracycline.
      MICs have been determined by GC agar dilution method. Azithromycin is more active
      than erythromycin on all N. gonorrhoeae patterns with a two log 10 difference for
      MIC50 and MIC90 (p < 0.0001). Because of pharmacokinetic properties and activity
      against Chlamydia trachomatis and urogenital mycoplasms often associated with N.
      gonorrhoeae, azithromycin is a good alternative for the treatment of genital
      infections.

PMID- 7567116
TI  - [Extra and intracellular activity of dirithromycin against Mycobacterium avium].
AB  - The in vitro activity of dirithromycin alone and in combination with clofazimin,
      ethambutol and rifabutin was tested against thirty strains of Mycobacterium avium
      isolated from patients. Extracellular activity of dirithromycin was assessed by
      determining MICs using the radiometric methodology in 7H12 broth at two pHs 6.8
      and 7.4. The MICs obtained at pH 7.4 were 3 to 4 more dilutions lower than those
      obtained at pH 6.8. Activity of pairs of antibiotics was measured using the FIC
      indices. Dirithromycin-clofazimin combination demonstrated the most important
      additive effects and even produced synergic effect against 5 of 30 strains.
      Studies of intracellular bacteria showed that the most effective bactericidal
      combination was dirithromycin, clofazimin and ethambutol together.

PMID- 7567118
TI  - [Must pefloxacin and norfloxacin be studied separately against bacteria isolated
      from urinary tract infections by the API-ATB method?].
AB  - 2113 bacterial strains were isolated from urinary tract infections in 1992 in 133
      French pathology laboratories, 2069 strains were tested using the API-ATB method
      and the UR-14030 system including NFX and an additional test for PFX. Frequencies
      of susceptible (S), intermediate (I) and resistant (R) strains to PFX and NFX
      were respectively (%): 83.3; 8.6; 8.1 and 83.1; 9.5; 7; 4. Overall rate of
      concordance (C), SS, II and RR, between the two antibiotics reached 92.8, minor
      discrepancies (Dm), SI, IS, RI and IR, 6.3 and major discrepancies (DM), SR and
      RS, 0.9 (K = 0.82). For Enterobacteriaceae (n = 1830), frequencies of strains S,
      I and R were: 90.4; 5.9 and 3.7 with PFX and 90.4; 6.1 and 3.5 with NFX.
      Percentages of C, Dm and DM were 95.1; 4.4 and 0.5 respectively. The Lee test
      showed that results obtained with NFX and PFX were equivalent (p < 0.001)
      allowing to consider that the test of NFX is sufficient to conclude for
      susceptibility or resistance to both antibiotics using the API-ATB method and the
      UR-14030 system. Dm were probably related in some cases to a low level resistance
      mechanism and to the difference between the higher breakpoints (4 micrograms/ml
      for PFX and 8 micrograms/ml for NFX). DM might be due to artefacts related to the
      bacterial inoculum size or to the antibiotic concentration obtained in the
      cupules.

PMID- 7567117
TI  - [In vitro activity of carbapenems (biapenem, imipenem and meropenem) and some
      other antibiotics against strict anaerobic bacteria].
AB  - During 1994, the in vitro antibiotic susceptibility of 306 anaerobic bacteria was
      performed in 4 hospitals, by the reference agar dilution method. Among the 129 B.
      fragilis group strains, only two B. fragilis strains were resistant to the three
      carbapenems and all beta-lactams, even combined with beta-lactamase-inhibitors
      while metronidazole resistance could not be detected. Evolution in antibiotic
      resistance rates could be assessed only for piperacillin whose resistance rates
      increased to 20%. beta-lactamase production was detected respectively for 27% of
      Prevotella and 17% of Fusobacterium strains. No beta-lactamase activity was seen
      among Gram positive anaerobes. On the whole anaerobic strains resistance rates
      were: biapenem, imipenem, meropenem and piperacillin-tazobactam 0.7, amoxicillin
      clavulanic acid or metronidazole 2, piperacillin 11.3, amoxicillin 31%,
      respectively. The three carbapenems demonstrated a good in vitro activity against
      most anaerobes with few differences between them.

PMID- 7567119
TI  - FT-IR spectroscopy study of perturbations induced by antibiotic on bacteria
      (Escherichia coli).
AB  - Fourier transform infrared spectroscopy (FT-IR) is an analysis method which over
      the spectral absorption, gives information about the molecular structures of
      systems. Recently, this method is widely used to the investigation of complex
      systems like cells and bacteria. Characteristic of FT-IR spectrum of bacteria
      depend closely to physiological and culture parameters. In this study, the
      infrared bands of intact bacteria are first tentatively attributed to the
      contribution of the cellular components. Secondly are compared the FT-IR spectra
      of Escherichia coli bacteria before and after treatment at sub-inhibitrice
      concentrations (< or = MIC) at penicillin A, penicillin G and nalidixic acid. The
      observed spectral perturbations are closely depending on the antibiotic treatment
      and are observed even if bacterial cell mass is far away from cell death. On the
      other hand, this spectral changes are related to the known mode of action of the
      used antibiotic.

PMID- 7567120
TI  - [Detection of beta-lactamases resistant to inhibitors (IRT) by the disk diffusion
      method].
AB  - 85 E. coli strains producing various beta-lactamase were studied: TEM low level:
      n = 11, TEM high level: n = 4, oxacillinase (OXA): n = 5, cephalosporinase (CASE)
      +/- TEM: n = 5, inhibitor resistant TEM (IRT) n = 50, IRT+TEM: n = 3, IRT+ CASE:
      n = 7. Their susceptibility to amoxicillin (AMX), amoxicillin+clavulanate (AMC),
      ticarcillin (TIC), ticarcillin+clavulanate (TCC), piperacillin (PIP),
      piperacillin+tazobactam (TAZ), mecillinam (MEC), cephalotin (CF), cefoxitin (FOX)
      et ceftazidime (CAZ) were evaluated by a disk diffusion method, in order to
      determine the resistance pattern which allows a reliable detection of IRT
      producing strains. The phenotype AMX R, TIC R, AMCI/R, TCCI/R et CFS was observed
      in 46 out of 53 IRT +/- TEM strains, 4/5 of OXA strains and 1/11 of TEM low level
      strains. A better sensitivity could be obtained by a modification of breakpoints
      for AMC, TCC and CF, however OXA-producing strains remain indistinguishable from
      IRT-strains.

PMID- 7567121
TI  - [Comparison of different phenotypic methods with polymerase chain reaction (PCR)
      for the detection of resistance to oxacillin in coagulase negative
      staphylococci].
AB  - The mecA gene which confers the oxacillin resistance has been searched by PCR in
      290 (124 positives, 166 negatives) coagulase-negative staphylococci (CNS)
      belonging to twelve species. The results were compared with the oxacillin MIC
      values obtained by agar dilution (4% NaCl) or by the ATB STAPH method (Api
      bioMerieux; 0%, 2%, 5% NaCl) and growth inhibitory diameters obtained by agar
      diffusion with an oxacillin disk placed at 30 degrees C without NaCl, or at 35
      degrees C in presence of 2% or 5% NaCl. Sensitivity of oxacillin resistance
      detection depends upon the salt concentration and the method used. The optimum
      concentration is 2%. With this concentration, the Api ATB test appears as the
      more performant (sensitivity: 89.8%). Search for the mecA gene by PCR represents
      a very interesting method that detects 96.9% of the oxacillin-resistant CNS
      strains.

PMID- 7567122
TI  - [Identification of a cephalosporinase susceptible to clavulanic acid in a
      clinical strain of Serratia fonticola].
AB  - We analyzed the beta-lactamase production of a Serratia fonticola isolated for
      its resistance to cefuroxime (Minimum Inhibitory Concentration > 256 mg/l) in
      December 1993 from a patient hospitalized in Meaux. The wild strain was resistant
      to amoxycillin but sensitive to augmentin, that suggested the production of a
      beta-lactamase susceptible to clavulanic acid. For the wild strain, beta
      lactamase production was inducible and only one enzyme with an isoelectric point
      of 8.12 was detected. beta-lactamase production was 16 mU/mg for non-induced
      extracts and ranged from 100 to 230 mU/mg in the presence of inducing beta
      lactams (enzyme activity was measured with penicillin G as substrate). On a
      Szybalski gradient a constitutive strain was obtained. Its enzyme production was
      13,000 mU/mg. The kinetics and isoelectric points of the enzymes produced by the
      two strains were identical. This beta-lactamase hydrolyzes penicillins
      (amoxycillin: Vm = 60 relative to penicillin G = 100, ticarcillin: 15), first
      generation cephalosporins (cephalothin Vm = 930). However, this enzyme hydrolyzes
      efficiently oxyimino-cephalosporins: cefuroxime (Vm = 70) and cefotaxime (Vm =
      120), but cephamycins are not substrates. Clavulanic acid has a very good
      affinity for this beta-lactamase (Ki = 0.09 microM) which is inactivated
      progressively (I50 = 0.045 microgram/ml). These properties shows some
      similarities with those of the class A beta-lactamases of P. vulgaris RO104 (pI =
      8.3), P. penneri 14HBC (pI = 6.65) and the plasmid-mediated extended-spectrum MEN
      1 (pI = 8.4).

PMID- 7567123
TI  - [Phenotypes of resistance to antibiotics of the most frequently isolated strains
      in five specialized hospital centers. Multicenter study].
AB  - Antibiotic susceptibility of 948 bacterial strains isolated from varied samples
      essentially proceeding from urinary infections in five Paris psychiatric
      Hospitals was determined by disk diffusion method. E. coli, P. mirabilis,
      Klebsiella spp., P. aeruginosa et S. aureus are the predominant bacteria. 40% of
      S. aureus are methicilline resistant. Enterobacteriaceae are progressively
      becoming resistant to aminopenicillines, but remain sensitive to third generation
      cephalosporines. They are still susceptible to first generation quinolones. At
      least, if no resistance of P. aeruginosa to imipeneme has been reported, 30% of
      strains are resistant to ciprofloxacine. Resistance phenotypes to antibiotics of
      the strains isolated in patients from psychiatric Hospitals are located between
      those observed in out patients and in patients from general Hospitals. However,
      we noticed a worrying evolution of resistance to those encontered in psychiatric
      Hospitals. Therefore, a multiresistant strains emergence monitoring must be
      carried out regulary.

PMID- 7567124
TI  - [Detection of beta-lactamase in samples obtained after tonsillectomy in
      children].
AB  - Production of beta-lactamase was detected using a microbiological assay (Guts
      test) in samples of tonsils, and by in Haemophilus growing from the same samples
      of both tonsils obtained from 30 children aged 2 to 13 years (18 aged < 6 years
      and 12 aged > or = 6 years). Two pieces from each tonsil, core and superficial,
      were studied. The procedure included direct microscopic examination of smears,
      and culture to identify Haemophilus, beta-haemolytic streptococci and
      Streptococcus pneumoniae. Guts test was positive in tonsillar tissue obtained
      from 26 children (14 aged < 6 years and 2 aged > or = 6 years) (p < 0.01). In 10
      of them (9 aged < 6 years and 1 aged > or = 6 years) (p < 0.05) grew beta
      lactamase producer Haemophilus influenzae. One to three varieties of Haemophilus
      could be found in 28 children (11 with H. influenzae = 5 beta-lactamase +, 8 with
      Haemophilus parainfluenzae = 3 beta-lactamase +); Group A, C, or G streptococci
      in 5 children, but no strain of Streptococcus pneumoniae. No difference could be
      demonstrated between core and superficial samples: beta-lactamase activity was
      positive in superficial samples from 26 children and core samples from 24. Almost
      all bacteria described grew from superficial as well as (slightly but no
      significantly less) from core samples.

PMID- 7567125
TI  - [Dynamics of the nasal colonization by methicillin resistant Staphylococcus
      aureus in patients hospitalized in an intensive care unit].
AB  - Prospective study on MRSA nasal cariage was done during two months in an
      intensive care unit in Limoges University Hospital. Nasal swab specimens were
      taken daily and cultured on selective and non selective media. Sixty eight
      patients were included in this study (878 swab collected, 575 MRSA isolated).
      Patients mean age was 62 years and stay period mean was 12.3 days (median: 7
      days). Among these patients, 16 were already carrying MRSA when entering in the
      unit and 26 became positive for MRSA during their stay. The mean colonisation
      delay was 5.5 days (median 4 days). All patients, except one, have shown a nasal
      carriage during all their stay. During the study period, 17 patients became
      infected and only two patients neither carried nasal MRSA before and during
      infection. In all cases, glycopeptide treatment did not affect nasal carriage.
      Colonisation and infection risk factors were discussed.

PMID- 7567126
TI  - [Outbreak of infections of Klebsiella pneumoniae with extended spectrum beta
      lactamase in a hospital unit with a long and medium stay].
AB  - Fourteen extended-spectrum beta-lactamase (ES beta la) Klebsiella pneumoniae
      strains were isolated from 14 inpatients between February 1993 and February 1994,
      in a medium- and long-stay neurological unit. For this reason an epidemiological
      study was begun, based on strain typing and examination of patient files. Strain
      typing was carried out by two methods (i) the analysis of antibiotic resistance,
      showing 7 different antibiotypes among the 14 strains studied, (ii) the analysis
      of esterase and dehydrogenase electrophoretic polymorphism in polyacrylamide
      agarose gel. The method was checked by analysing 11 Klebsiella pneumoniae strains
      with wild phenotype for beta-lactam antibiotics, which were isolated during the
      same period in the same unit. Simultaneously 6 other strains isolated during the
      same period in some other units of the hospital were analysed. Nine
      electrophoretic types were found among the 31 strains (wild and ES beta las). The
      analysis of the results showed that 8 isolates of the group of 14 ES beta las had
      the same antibiotype and electrophoretic type. This demonstrates that one
      epidemic strain was responsible for two outbreaks, the first one in April and the
      second one in August-September. A case control investigation was carried out to
      define the risk factors of infection. Files were examined for the 14 infected
      inpatients and for 20 control inpatients from the same unit during the same
      period. Statistical analysis was performed with Epi Info software 5 (CDC
      Atlanta). Length of stay, dependence and malnutrition levels, and urinary
      sphincter disfunction were the most significant risk factors.

PMID- 7567128
TI  - [Molecular typing by pulsed field gel electrophoresis of Pseudomonas
      (Burkholderia) cepacia isolated from a nosocomial infection].
AB  - Because of the emergence of Pseudomonas (Burkholderia) cepacia, isolated among
      patients from an intensive care unit of the Hopital Pellegrin (Bordeaux), strains
      were studied in the aim to determine the source and the mode of transmission of
      the bacteria. The study was performed on 44 isolates of P. cepacia from 21
      patients (23 strains) or from the environment (16 isolates from ventilators and
      five from the distilled water used for these ventilators). Susceptibility to 23
      antibiotics of these strains and endonuclease restriction polymorphism on their
      total DNA were determined. Pulsed field gel electrophoresis was performed after
      digestion of the genomic DNA, using three restriction enzymes. Results obtained
      by analysis of genotypic characteristics demonstrated the clonal origin of the P.
      cepacia epidemy in the different intensive care units, but did not localize the
      source of the infection.

PMID- 7567127
TI  - [Bacteriological monitoring of the treatment of Pseudomonas aeruginosa infections
      with amikacin administrated at once-daily dosis in patients with cystic
      fibrosis].
AB  - The interest of the treatment with a single daily dose of amikacin (AMK) in
      cystic fibrosis (CF) patients with P. aeruginosa infections has been much
      debated. The aim of work was to study the efficiency of this treatment on (CF)
      patients with chronic bronchopulmonary P. aeruginosa infections previously
      treated for two weeks with the combination ceftazidime (CAZ 200 mg/day in 3 inj.
      IVD) and AMK (35 mg/day in one IV perf. of 30 minutes). The bacteriological
      supervision of this treatment was performed 1: by the determination of MICs
      before and after treatment, 2: by the decrease of P. aeruginosa colonization
      immediately after this treatment and during 11 months, 3: by the identification
      of P. aeruginosa strains with phenotypic methods (serotyping and antibiotyping)
      and with genotypic method (pulsed field gel electrophoresis). The use of AMK in a
      single daily dose in order to treat chronic lung infections colonized with P.
      aeruginosa susceptible to this antibiotic shows encouraging results as far as
      bacteriology is concerned: this treatment has given means to reduce colonization
      for a month in 15 of 18 patients. For 9 of the 18 patients, no P. aeruginosa
      strains were isolated for nine months. The serotyping and antibiotyping systems
      do not enable us to study the P. aeruginosa epidemiology. Genome macrorestriction
      fingerprinting of P. aeruginosa in pulsed field gel electrophoresis confirms that
      patient with CF were colonized with one or several clones. In our study no
      variation of these clones was noticed for the first eleven months. Genome
      macrorestriction fingerprinting appears to be one of the most effective methods
      for delineate strains of P. aeruginosa colonizing CF patients.

PMID- 7567129
TI  - [In vitro activity of disinfectants against bacteria isolated in water for
      hemodialysis].
AB  - The bactericidal and sporicidal activities of six disinfectants (Acetoper, Cidex,
      Phagoseptyl, Pyosynthene, Betadine, Sterlane) were studied against 21 bacterial
      strains recovered from hemodialysis machines, and against two bacterial spores.
      AFNOR methods were used (NF T. 72-151, NF T. 72-171 et NF T. 72-231). Only
      Acetoper presented a bactericidal and sporicidal activity. A disparity in
      bactericidal concentrations was observed among Gram negative bacteria. Phenolic
      compound (Phagoseptyl) was not influenced by interfering substances. pH have a
      clear effect upon Cidex and Betadine activities. Statistical analysis (variance
      and multiple comparisons test of Ryan-Einot) showed the significant role of the
      type of bacteria and the nature of disinfectants. These compounds were classified
      according to their increasing activity as following: Cidex, Sterlane,
      Phagoseptyl, Betadine, Pyosynthene, Acetoper.

PMID- 7567130
TI  - [Penetration of ceftriaxone (1 or 2 gr intravenous) into mediastinal and cardiac
      tissues in man].
AB  - Ceftriaxone penetration into heart tissues (valves, myocardium, auricles and
      pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after
      two regimens of ceftriaxone administration. Ten patients were given 1,000 g
      intravenously of ceftriaxone 30 min. before anesthesia. Ten other patients
      received the same dose and then a second 1,000 mg dose at the time of initiation
      of cardiopulmonary bypass. Similar and very satisfactory ceftriaxone tissue
      penetrations were observed in both groups. However, for some patients in the two
      groups and mainly in the sternal bone at the time of thorax closure, ceftriaxone
      levels in tissues were less than the MICs for some potential pathogens
      (Methicillin susceptible Staphylococcus aureus and Staphylococcus epidermidis).
      During the different steps of the surgical procedures all patients in both groups
      had tissue levels greater than the MICs for Gram negative aerobic bacilli, except
      for Pseudomonas spp.

PMID- 7567131
TI  - [Prevention of cariogenic dental plaque. Study of the structures implicated in
      the adhesion and coaggregation in Streptococcus mutans and Streptococcus
      sobrinus].
AB  - Cariogenic dental plaque may be assimilated to a biofilm resulting from the
      adhesion of S. mutans, then from the coaggregation of other streptococci, or
      other genus. We used a static monospecific biofilm model. Supports or bacteria
      were treated with inhibitors before adhesion in order to clarify the nature of
      adhesins responsible for the primary adhesion of S. mutans and S. sobrinus on
      Tygon. To determine the bindings of coaggregation, inhibitors were applied on one
      day-old biofilms. Analysis of effects were performed by automatic inoculator
      Spiral (Interscience) for microbiological methods, and by SEM JEOL 5400 LV for
      microscopic methods. In the aim of preventing adhesion and coaggregation,
      different traps were assayed:sugars, chemical inhibitors such as F- and EDTA
      salts. Of these, only the latter showed efficiency. This confirmed the role of
      bivalent mineral ions and electrostatic attraction forces in the adhesion and
      coaggregation of streptococci.

PMID- 7567132
TI  - [Isolation of an acid-alcohol resistant bacillus (BAAR) in the febrile HIV
      infected patients: Mycobacterium tuberculosis (MT) or Mycobacterium avium complex
      (MAC)?].
AB  - The detection of BAAR in HIV infected patients with CD4 < 100/mm3 and with an
      infectious syndrome urge on beginning an effective treatment against
      Mycobacterium tuberculosis and/or Mycobacterium avium Complex, before the results
      of the culture are known. Our purpose was to search clinical and biological
      features to angle directly the diagnosis towards a tuberculosis or not, and to
      start the most suitable treatment. This retrospective study, from 1986 to 1993,
      stated on 54 patients who had at least one sample with positive BAAR (blood,
      marrow, stools, sputum or urine cultures). From these cultures, MAC was isolated
      on 37 patients and BK on 17. The both groups were similar for age, sex, risk
      factor, number of opportunistic infections, delay between the date of AIDS and
      the discovery of a positive BAAR, and Ag p24. However, a significant difference
      in favor of a MAC disease exists regarding about: disseminated infections (92% vs
      53%), digestive troubles (57% vs 23.5%), anterior or concomitant CMV infection
      (49% vs 9%), isolation of BAAR in blood culture (54% vs 20%) or in stools culture
      (76% vs 33%), leucopenia (2850/mm3 +/- 1520 vs 4124/mm3 +/- 2232), anemia (Hb 9.1
      g/dl +/- 1.5 vs 10.1 g/dl +/- 1.6). The univariated analysis of results allowed
      us to conclude that the presence of one among those parameters must induce the
      prescription of a suitable treatment against MAC.

PMID- 7567134
TI  - Schistosomiasis and prostate cancer.
AB  - In endemic geographical areas schistosomiasis has been implicated as an
      etiological agent in the pathogenesis of bladder, colorectal and renal carcinoma.
      In particular bladder cancer commonly occurs in such geographic locations almost
      2 decades earlier than in non-endemic areas. A relationship between prostate
      cancer and bilharzial infestation is not established. This is a report of 3 cases
      of co-existent schistosomiasis and prostatic adenocarcinoma occurring in
      unusually young patients.

PMID- 7567133
TI  - Primary Hodgkin's disease of the lung.
AB  - Three cases of Hodgkin's disease presenting primarily in the lung are described.
      All 3 patients presented with respiratory symptoms and chest X-rays revealed
      discrete masses within the lung parenchyma. CT examination of the mediastinum did
      not reveal regional or generalized lymphadenopathy at the time of diagnosis in 2
      of the cases. A diagnosis of Hodgkin's disease was made on open lung biopsies and
      despite aggressive chemotherapy, 2 patients died within 2 yrs. The histological
      and immunocytochemical features of these cases were typical of that expected in
      Hodgkin's disease. However, the stated indolent course of primary pulmonary
      Hodgkin's disease is not invariable. Those patients with bilateral interstitial
      disease and systemic symptoms have a poor prognosis. Furthermore, it is difficult
      to exclude definitely lymph node involvement (although not enlarged) at the time
      of diagnosis. Since several cases described in the literature have concurrent
      and/or subsequent nodal involvement, the entity of primary pulmonary Hodgkin's
      disease without lymph node involvement is exceedingly rare.

PMID- 7567135
TI  - p53 protein immunoreactivity in cancers of the gallbladder, extrahepatic bile
      ducts and ampulla of Vater.
AB  - Immunohistochemical expression of the p53 protein was investigated in carcinoma
      of the gallbladder (n = 13), common bile duct (n = 7) and ampulla of Vater (n =
      9) using the polyclonal, CM1, and monoclonal, DO7, antibodies (Novocastra). This
      was compared with cases of chronic cholecystitis (n = 11) and preneoplastic
      lesions of the gallbladder (n = 4) and ampulla (n = 3). Nuclear immunostaining
      for p53 protein was found only in the poorly differentiated adenocarcinomas of
      the gallbladder (n = 9) and were associated with a shorter patient survival
      period (median: 18.6 mths). The moderately differentiated adenocarcinomas (n = 4)
      did not show p53 immunostaining and were associated with a longer median survival
      period (26 mths). The gallbladder dysplasias and adenoma also had no p53 protein
      immunoreactivity. The common bile duct carcinomas did not stain for p53. Focal
      p53 immunoreactivity was present in only one (11%) of the cases of ampullary
      carcinoma and in one (9%) of chronic cholecystitis. In summary, increased p53
      immunostaining was associated with reduced patient survival and found more
      frequently in poorly differentiated adenocarcinoma of the gallbladder but not in
      the better differentiated carcinoma, chronic cholecystitis or preneoplastic
      lesions of the gallbladder. The differences in p53 immunohistological expression
      between gallbladder, common bile duct and ampullary carcinomas justify further
      investigation into the molecular mechanisms responsible for their development.

PMID- 7567136
TI  - Pathology of lymphoid organs in low birth weight infants subjected to antigen
      related diseases: a morphological and morphometric study.
AB  - The pathology of lymphoid organs in 38 low birth weight (LBW) human infants has
      been evaluated by morphological and morphometric features. The gestational ages
      of infants ranged from 22 to 32 wks and their age at death varied from 1 hr to
      153 days post partum. Infants were divided into 3 groups: 1) without antigenic
      effects, 2) with mild (bronchopneumonia), and 3) with severe antigenic effects,
      mainly sepsis. In mildly affected LBW infants, the fetal type of the immune
      reaction was found. It continued during the period studied (till 5 mths) and was
      manifested in the reaction of macrophages and the transformation of lymphocytes
      to lymphoblasts. Reactive centres of follicles and mature plasmocytes were not
      found. During the first months of postnatal development, an increase in the
      amount of lymphocytes in the lymphoid organs and in the rate of proliferation of
      reticular epithelium and a decrease in the area of the cortex in the thymus were
      found in all infants. In severely affected infants, the number and the size of
      follicles in the spleen decreased significantly and the total number of cells
      decreased more than 3 times. Similar changes were found in lymph nodes. These
      changes as well as the weak reaction of the thymus are the main features of the
      insufficiency and fast devastation of the lymphoid system. A compensatory
      increase in the number of neutrophils and eosinophils in the red pulp of the
      spleen and lymph nodes was found after the second week.

PMID- 7567137
TI  - Early onset of multiple sclerosis with autopsy confirmation.
AB  - A female had her first generalized epileptic seizure at age 11 yrs. Apart from
      intermittent seizures she remained well until 15 yrs of age when she developed
      double vision, unsteadiness and bilateral plantar responses which resolved
      spontaneously. Brain MRI scan at this stage revealed changes typical of multiple
      sclerosis. She died at 17 yrs of age from asthma and epilepsy. Autopsy confirmed
      the presence of multiple sclerosis and showed the disease to be very active. We
      consider it likely that multiple sclerosis was present at the age of 11 yrs when
      she had her first epileptic seizure. This case of multiple sclerosis is presented
      because of the rarity of the early age of onset, unusual presentation with
      epilepsy, marked activity of disease and early death. Also it is uncommon to have
      autopsy confirmation of such disease.

PMID- 7567138
TI  - Experimental models in pulmonary pathology.
AB  - Because of the cellular complexity and spatial organization of the lung,
      investigation of the pathogenesis of human pulmonary diseases relies to a
      considerable extent upon the use of animal models. In this review, the author
      examines new models and new applications of existing models of pneumonia, asthma,
      emphysema, interstitial lung disease and neoplasms in laboratory mice and rats.
      Studies of such models may assist in the development of appropriate strategies
      for early diagnosis and intervention.

PMID- 7567139
TI  - Transfusion reaction due to Yersinia enterocolitica and review of other reported
      cases.
AB  - A 26 yr old woman was transfused after her baby was delivered by Caesarian
      section. During transfusion of the second pack of concentrated erythrocytes, she
      became acutely febrile. She then became shocked and gravely ill. Yersinia
      enterocolitica serogroup O:3 was recovered by blood culture from the patient and
      from the remnant of the bag of blood (but not the segments). The blood donor had
      suffered no illnesses. The patient received intensive treatment including
      antibiotics and made a slow recovery. Yersinia enterocolitica contaminated blood
      is a rare cause of potentially fatal post transfusion septicemia. Prompt
      recognition of the endotoxemia with cessation of the transfusion of the
      contaminated blood, although desirable does not seem to alter the outcome. There
      is no known effective measure to prevent such reactions.

PMID- 7567141
TI  - Simple computer spreadsheet for standardized interpretation of oral glucose
      tolerance tests.

PMID- 7567140
TI  - Lupus anticoagulant in the elderly may be associated with both quinine and
      quinidine usage.
AB  - Thirty-one patients aged over 60 yrs and with lupus anticoagulant (LA) were
      reviewed for their drug intake. Twenty-three (73%) were taking cinchona
      alkaloids, 10 (32%) quinine for night cramps, 11 (35%) quinidine for cardiac
      arrhythmia and 2 (6%) were taking both. These frequencies of drugs usage differed
      significantly from age and sex matched controls (p < 0.001). Five patients had
      features suggestive of the antiphospholipid syndrome. Repeat testing showed
      persistent LA activity in all but 2 of 5 patients in whom the relevant drug had
      been ceased. This is the first description of a possible causal association
      between LA and quinine therapy.

PMID- 7567142
TI  - The diagnosis and follow-up of porphyria.
AB  - This review details an approach to the biochemical diagnosis and follow-up of
      porphyria. We discuss the problems of diagnosis of both symptomatic patients
      suspected of porphyria and patients being investigated because of a family
      history of porphyria. High performance liquid chromatography plays a major role
      in the investigation of these patients. Molecular biology is emerging as a useful
      tool in further defining this group of diseases.

PMID- 7567143
TI  - Paraquat and diquat interference in the analysis of creatinine by the Jaffe
      reaction.
AB  - Paraquat and diquat were shown to interfere significantly in the measurement of
      plasma creatinine by the alkaline picrate (Jaffe) reaction in a young man who
      ingested a massive dose of a mixture of the 2 herbicides. It is likely that these
      bipyridylium compounds react in a manner similar but at different rates compared
      with creatinine in the Jaffe reaction.

PMID- 7567145
TI  - Comparison between three PCR methods for detection of human cytomegalovirus DNA.
AB  - Three methods for the detection of human cytomegalovirus DNA using the polymerase
      chain reaction (PCR) were compared with and without a wax-mediated hot start.
      This process yielded a 10-fold increase in the sensitivity of the detection of
      specific DNA. The PCR method chosen as most suitable for subsequent testing, when
      applied to urine samples from patients with AIDS, gave a higher proportion of
      positive results than either the shell vial assay or conventional cell culture.
      On the basis of these results, further work is being carried out to evaluate the
      value of the PCR, when the results are expressed quantitatively, in the
      laboratory diagnosis of cytomegalovirus infection in patients with AIDS.

PMID- 7567144
TI  - A high efficiency method for purification and assay of bee venom phospholipase
      A2.
AB  - Phospholipase A2 (PLA2) is the main allergen of hymenopteran venoms. We describe
      a highly efficient reverse phase high performance liquid chromatographic method
      (HPLC) for isolating PLA2 from crude bee venom. This method removes all
      detectable contaminants such as melittin from PLA2 while preserving the hemolytic
      action of PLA2. In addition we describe a simple functional assay of PLA2 based
      on its propensity to cause hemolysis of guinea pig red blood cells. These
      techniques are particularly well suited to the isolation and assessment of PLA2
      of venoms which are available in limited quantities.

PMID- 7567146
TI  - Meningitis caused by Streptococcus pneumoniae showing high level resistance to
      penicillin.
AB  - A case of meningitis caused by a strain of Streptococcus pneumoniae (SPn) showing
      high level resistance to penicillin is described. The patient responded to a
      combination of high dose penicillin and ceftriaxone. After reviewing the
      Australian situation and the world literature, we propose that empiric treatment
      of SPn meningitis in Australia should consist of high dose penicillin plus a
      third generation cephalosporin, with appropriate modification once the
      identification of the organism and its susceptibilities are confirmed.

PMID- 7567147
TI  - Comparison of antigen detection, polymerase chain reaction and culture for
      detection of Chlamydia trachomatis in genital infection.
AB  - An in-house polymerase chain reaction (PCR) test using ribosomal RNA gene primers
      was compared with chlamydia antigen detection (DIF) and culture for the detection
      of Chlamydia trachomatis. Five hundred and forty-eight fresh (unstored) genital
      swabs and 174 urines (collected at the same time) from patients attending a
      sexually-transmitted diseases clinic were examined. PCR, DIF and culture detected
      chlamydia in 43, 35 and 42 swabs respectively from the 43 resolved positive
      cases. The specificity on the resolved negative specimens was 100% for each of
      the tests. From the urines, PCR and DIF detected the organism in 16 and 15 cases
      respectively of the 23 resolved positive males tested but in only 2 and 3 cases
      respectively of the 9 resolved positive females tested. Specificities were 100%
      in all cases. Both of the non-culture tests manifested problems with urine due to
      inhibitory activity (in PCR test) or excessive debris (in DIF test) in about 5%
      of the specimens. Culture of the urines yielded sensitivities of 40% in the males
      and 22% in the females. Overall PCR was more sensitive than either culture or DIF
      on both urethral and cervical swabs and urines. The urines yielded less than
      three-quarters the number of positives that was obtained from the swabs and were
      considered to be an unsatisfactory specimen for chlamydial diagnosis. It is
      concluded that PCR is a satisfactory alternative to culture on genital swabs and
      may be preferable in situations where the viability of the organisms is in
      question. DIF remains useful because of its speed and simplicity but is
      insufficiently sensitive to be relied upon by itself.

PMID- 7567148
TI  - The MicroScan WalkAway diagnostic microbiology system--an evaluation.
AB  - The MicroScan WalkAway is an automated bacterial identification and
      susceptibility testing system that has only recently been marketed in
      Australasia. We evaluated the performance of the instrument using MicroScan Rapid
      fluorescent panels to determine the identity and antibiotic susceptibilities of
      100 Gram negative and 100 Gram positive organisms representing both common
      clinical isolates and selected organisms of interest. MicroScan results were
      compared with those obtained by conventional biochemical identification, and
      antibiotic susceptibility testing using agar dilution following the National
      Committee on Clinical Laboratory Standards guidelines. MicroScan and reference
      identifications were in agreement for 93% of Gram negative organisms. MicroScan
      results were available within 2 hrs. Additional tests were required to confirm
      the identity of 9 isolates but on only 2 occasions would a definitive
      identification been delayed beyond 24 hrs. Very major or major discrepancies were
      seen in 2% and minor discrepancies in 8% of Gram negative susceptibility tests.
      Susceptibility results were available within 7 hrs but could not be obtained for
      13 slow growing organisms. With Gram positive organisms MicroScan agreed with the
      reference identification of 87% of isolates cultured on horse and 90% of those
      cultured on sheep blood agar. Discrepancies that occurred in the identification
      of some streptococci made us question the suitability of MicroScan as the sole
      means of identifying these organisms. All identifications were available within
      24 hrs and the requirement for additional tests was minimal. Susceptibility
      results closely matched those obtained by agar dilution with < 1% major and 7%
      and 9% minor discrepancies occurring with sheep and horse blood
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567149
TI  - Clinical utility of the polymerase chain reaction to diagnose Mycoplasma
      pneumoniae infection.
AB  - The diagnosis of Mycoplasma pneumoniae infection currently relies on serological
      methods which may be slow to produce diagnostic results and may be inconvenient
      for both the clinician and the patient. This study was designed to assess whether
      or not the polymerase chain reaction (PCR) is a useful additional diagnostic
      method. Comparison was therefore made with serology as it is routinely practiced.
      PCR was used to examine for the presence of M. pneumoniae DNA in throat swab
      specimens obtained from 99 hospitalized patients investigated for a range of
      respiratory pathogens including M. pneumoniae. PCR detected M. pneumoniae DNA in
      24 adults and 25 children, which is significantly more than the 32 patients found
      to be antibody positive by the particle agglutination test (p = 0.001). M.
      pneumoniae DNA was not detected in any of the throat swabs from 32 apparently
      healthy volunteers. PCR inhibitors were not detected in any of the samples
      tested. Significantly more children (88%) than adults (38%) were found to be anti
      mycoplasma antibody-positive (p < 0.0001). Routine clinical practice was
      reflected in the fact that 56 patients (57%) had indeterminate serological
      results because only single sera were obtained. The sensitivity and specificity
      of PCR were assessed to be 92% and 98% respectively, using a combination of
      serological and clinical data as the benchmark. PCR appears to have advantages
      over serological testing, both with respect to accuracy and convenience of single
      specimen testing. The poor performance of serological tests in adults makes PCR
      especially useful in this age group.

PMID- 7567150
TI  - Human trichostrongyliasis in Queensland.
AB  - Trichostrongylus infection, an uncommonly reported zoonosis in Australia, is
      common in parts of the world where there is close human contact with herbivorous
      animals. We report 5 cases diagnosed in our laboratory since 1992. Over this
      period the laboratory has conducted over 46,000 parasitological examinations on
      feces. All 5 cases were investigated for fecal parasites following detection of a
      blood eosinophilia. Two of the 5 cases complained of mild abdominal discomfort
      and diarrhea. It is likely that all obtained their infection following ingestion
      of contaminated unwashed vegetables which had been fertilized with animal manure.
      Four of the cases acquired their infection in Queensland and the fifth may have
      become infected in rural Victoria. All were treated with pyrantel embonate with
      resolution of the eosinophilia. Follow up fecal specimens showed no parasites.
      Patients were instructed on the mode of transmission and advised to thoroughly
      wash any uncooked vegetables prior to ingestion. In our cases, goats and horses
      were possibly implicated. No published reports of Trichostrongylus spp. in humans
      in Australia have occurred since the 1930s and it may be more common in Australia
      than is recognized. The infection may be missed because patients are asymptomatic
      or have mild gastrointestinal symptoms or only a blood eosinophilia.
      Trichostrongylus eggs may also be mistaken for hookworm eggs. It is important
      therefore to distinguish these infections from hookworm infection as the modes of
      transmission, management and advice regarding prevention differ.

PMID- 7567152
TI  - Differential in situ hybridization for determination of mutational specific
      expression of the p53 gene in human hepatoma cell lines.
AB  - The codon 249 mutation specific expression of the p53 gene was determined in 7
      human hepatocellular carcinoma (HCC) cell lines. Two 20-base oligomers
      complementary to bases 872-891 of human p53 cDNA with a single nucleotide
      difference in the third position of codon 249 were end-labelled with biotin
      conjugated dATP using terminal deoxynucleotidyltransferase (TdT). The hybridized
      oligomer was visually detected in situ using streptavidin-alkaline phosphatase
      (AP) conjugate and AP substrate. Expression of the codon 249 mutant p53 was
      steady in PLC/PRF/5 and Mahlavu cells (derived from African patients), while
      Huh4, Huh6, Huh7 and HCC-M cells (derived from Japanese patients) expressed only
      the codon 249 wild-type p53. The transcripts of the p53 gene were undetectable in
      Hep3B cells (derived from an American patient). Hybridizations of the codon 249
      specific oligomers were specific to the p53 transcripts, since the cells that
      expressed p53 gene homogeneously were stained in the cytoplasm only by
      differential hybridization with a codon 249 specific oligomer; moreover,
      hybridization with a labelled oligomer non-complementary to the p53 cDNA showed
      nuclear stainings. Thus, detection of the codon 249 mutant p53 mRNA by
      differential in situ hybridization is a specific method for studying the mutation
      specific expression of the p53 gene in liver cancers at the cellular level, while
      simultaneously visualizing the cell morphology. The results also support the
      notion that the p53 gene codon 249 mutation may have etiological implications
      involving HCC from various geographic areas.

PMID- 7567151
TI  - Immune responses during an Antarctic summer.
AB  - The immune status of 29 members of the Australian National Antarctic Research
      Expeditions (ANARE) was investigated before, during, and after a 56 day summer
      voyage to Antarctica and correlated with psychological and physiological
      parameters. All subjects were healthy. Expedition personnel demonstrated
      decreased cell mediated immune responses (CMI) assessed by the CMI Multi-test;
      21% were hypoergic. The major associated observation was a significant negative
      correlation with anxiety in Antarctica. However, perceived anxiety was greater
      before and after the voyage. No significant changes were found in T and B
      lymphocyte subsets, immunoglobulin and complement components and cutaneous blood
      flow, nor was there any clinical evidence of illness. Of the hormones examined
      only cortisol was low predeparture which may reflect increased perceived anxiety
      at that time. Changes in immune control mechanism were apparent as shown by
      reduced CMI responses and lowered tetanus antibody levels. Stress factors are
      postulated to induce depression of the immune response in Antarctica. The
      association with anxiety suggests that brain peptides or associated cytokines may
      have a role in mediating these immune events. Such alterations in immune status
      have implications for health management in isolated and extreme conditions.

PMID- 7567153
TI  - The Sebastian platelet syndrome. Report of the first native Saudi Arabian
      patient.
AB  - Sebastian platelet syndrome is an hereditary thrombocytopenia with giant
      platelets and inclusion bodies in the granulocytes consisting of dispersed
      filaments, clusters of ribosomes and a few segments of rough and smooth
      endoplasmic reticulum at the ultrastructural level, similar to those observed in
      Fechtner syndrome (a variant of the Alport syndrome)--Sebastian platelet syndrome
      lacks the additional clinical features such as high frequency deafness,
      congenital cataract, and chronic interstitial nephritis. Here we report the
      fourth case worldwide and the first of an Arabian ancestry.

PMID- 7567154
TI  - Synchronous parotid myoepithelioma and Warthin's tumor.
AB  - We present a case of an 84 yr old man who underwent resection of a slowly
      enlarging parotid mass. Macroscopic examination of the lesion revealed 2 distinct
      tumor foci which were shown histologically to be a typical Warthin's tumor with a
      separate tumor composed entirely of clear cells. Immunohistochemical studies of
      the clear cell tumor confirmed its myoepithelial nature. This is the first
      documented case of a coexistent Warthin's tumor and a myoepithelioma.

PMID- 7567155
TI  - Malignant pilomatrixoma of the scalp.
AB  - A 33 yr old man with a history of pilomatrixoma of the scalp, presented 5 mths
      later with a metastatic undifferentiated carcinoma in a submandibular lymph node.
      The cutaneous and lymph node tumors showed close histological similarity and
      features of malignancy. Investigations over 30 mths excluded a primary neoplasm
      elsewhere and consequently led to the diagnosis of malignant pilomatrixoma. These
      tumors are rare and most often located on the scalp. Most of the affected
      patients are middle age males. Wide excision is advised to avoid recurrences.

PMID- 7567156
TI  - Tension pneumocephalus--a rare complication of radiotherapy in nasopharyngeal
      carcinoma.
AB  - A patient with nasopharyngeal carcinoma (NPC) treated by radiotherapy developed
      tension pneumocephalus due to a naso-cranial fistula. The fistula was due to a
      pathological fracture at the base of skull affected by bone necrosis. The
      clinical features, neuro-radiological and post-mortem findings are presented.
      This is the first case report of pneumocephalus in association with NPC. The
      brain showed florid subarachnoid and intraventricular air collection under
      tension, low grade meningitis, foreign body giant cell reaction in the arachnoid
      membrane and multifocal cerebral infarction. Late radiation necrosis was also
      found in the left temporal lobe. The cause of the tension pneumocephalus in
      relation to radiation bone necrosis and the possible role of pneumocephalus in
      producing the multifocal cerebral infarction are discussed. The more common
      radiation necrosis of brain is also discussed. The pathogenesis of the
      pneumocephalus in this patient is distinctly different from the more common
      causes such as head injury and surgery.

PMID- 7567157
TI  - Postoperative uterine granulomata following endometrial resection.
AB  - Granulomatous endometritis is an uncommon condition. We describe a case in which
      the granulomata were related to the previous endometrial resection. The
      importance of recognizing this entity is to avoid confusion with other causes of
      uterine granulomata and thus preventing inappropriate therapy being instituted.

PMID- 7567158
TI  - David Fitzpatrick's histopathology slide collection.

PMID- 7567159
TI  - [Histopathologic problems in non neoplastic disease of the vulva].

PMID- 7567160
TI  - Malignant hypomelanotic melanoma of mules. A histologic, immunohistochemical and
      ultrastructural study of a case with unknown primary site and widespread
      metastases.
AB  - An unusual case of malignant hypomelanotic melanoma occurred in a 15-year-old
      gray mantle mule with unknown primary site and widespread metastatic growth is
      described. An ante-mortem examination, the presence of subcutaneous nodules was
      noted; histologically they are constituted by spindle or polygonal-shaped tumour
      cells with rare black granules in the cytoplasm; the immunohistochemical
      procedures showed a large expression of S-100, vimentin and HMB-45 antibodies,
      suggesting thus a diagnosis of malignant melanoma. Ultrastructural findings,
      obtained on formalin-fixed paraffin-embedded material, showed characteristic
      melanosomes and irregular fibrillary centers in nuclei of neoplastic cells. At
      post-mortem examination, other nodular mostly melanotic lesions were appreciable
      in lungs, kidneys, brain, liver, pancreas, spleen, lymph nodes and muscles. The
      importance of immunohistochemical and ultrastructural findings for the
      differential diagnosis of this neoplasm is emphasized.

PMID- 7567161
TI  - [Pulmonary malformations associated with congenital cardiopathy].
AB  - The authors describe, in a series of 132 pediatric autopsies in the period
      January 1979-December 1994, the associations between congenital cardiopathies and
      pulmonary malformations. These latter were present in 13 of 46 cases (34.8%) in
      which cardiopathy was associated to a malformation of other discricts. In 9 of
      cases was exclusively interested the lung, while in the remaining 4 cases also
      other organs presented anomalies. The lung malformations observed were
      represented in 12 cases by supernumerary scissures with conjuncted cardiac septal
      system defects; in one case an alveolar dysplasia was associated to a previous
      Botallus duct. None of the 8 malformative syndromes, due to chromosomopathies,
      showed lung malformations. Examining the sequential chronological phases of the
      development of the two apparatus, the Authors hypothesize a common
      etiopathogenesis in both malformations, due to the isochronous action of the same
      intra-uterine pathogenic noxa, favoured by the topographic relationships of the
      two systems. Conversely, seems unlike the action of genetic damages, although
      either in genetically determined, or intra-uterine acquired, malformative
      syndromes, the pulmonary defects are almost exclusively represented by anomalies
      in the scissures formation.

PMID- 7567162
TI  - [Tumor and tumor-like benign mesenchymal lesions of the breast].
AB  - All the spectrum is encompassed of those miscellaneous pathologic entities
      occurring in the mammary stroma which are on record up to date other than "mixed
      fibroepithelial" tumors (fibroadenomas and phyllodes tumors) and tumors both
      "pure" and "mixed" originating from myoepithelium (adenomyoepitheliomas and
      pleomorphic adenomas). Also they were excluded those dysreactive-autoimmune
      diseases (sarcoidosis, sclerosing lymphocytic lobulitis, lobular granulomatous
      mastitis) and those inflammatory-infectious conditions (tuberculosis,
      actinomycosis, foreign body reactions, Mondor's disease) which can mimick breast
      tumors clinically or on image analysis, but on the contrary not evoking the idea
      of a tumor on histology. Specifically, inflammatory pseudotumor,
      myofibroblastoma, leiomyoma, neurinoma/neurofibroma, benign fibrous histiocytoma,
      hemangiopericytoma, fibromatosis, nodular fascitis, variants of lipoma,
      mesenchymoma, amartoma and its variants, hemangiomas, pseudoangiomatous
      hyperplasia of stroma, amyloid tumor, granular cell tumor, are consecutively
      described and discussed, with a large list of references enclosed to each rubric.
      Most of the pictures are taken from personally observed lesions of the breast.
      Only few pictures referred to are from their analogue lesions which occurred in
      soft parts of other locations, with specific mention of that when it was the
      case. Of note after reviewing the literature the fact that no glomus tumor, nor
      Kaposi's sarcoma either sporadic or in the context of any immunodeficiency, nor
      myelolipoma has been recorded yet.

PMID- 7567163
TI  - Can a specifically-aimed pathologic classification overcome the difficulties in
      defining HIV-associated lymphomas?
AB  - High grade B-cell systemic lymphomas in HIV-infected patients exhibit pleomorphic
      features as well as some overlap between established histologic subtypes thus
      highlighting the difficulties in defining them precisely by making use of the
      classifications for non-Hodgkin's lymphomas (NHL) proposed before the AIDS
      epidemic. A series of HIV-associated systemic lymphomas including 114 NHL and 25
      Hodgkin's disease (HD) cases were morphologically and immunopheno-genotypically
      investigated at the Centro di Riferimento Oncologico, Aviano, Italy during a
      period of nine years. The International Working Formulation (WF) for NHL, the
      updated Kiel Classification and, later, morphologic variants of high grade B-cell
      NHL have been adopted in order to obtain a more detailed and specific
      histopathologic description of HIV-associated lymphomas. As a consequence of
      morphologic data, and considering also pathogenetic aspects as derived from
      literature, we have attempted a pathological categorization of HIV-associated
      systemic lymphomas based on the recognition of two main groups: the "blastic"
      cell group and the "anaplastic" one, both including specific cytomorphologic
      subtypes with, possibly, aggressive HD subtypes within one of them. This
      categorization uses the WF, the updated Kiel system, and the morphologic variants
      of high-grade lymphomas, and provides a provisional category for cases with
      intermediate morphologic features. Thus other histologic subtypes, such as small
      noncleaved cell (Burkitt) and immunoblastic lymphomas, can be defined in a more
      accurate way. The clear-cut placement of "anaplastic" cell lymphomas, including
      anaplastic large cell (CD30/Ki-1+) lymphomas, including anaplastic large cell
      (CD30/Ki-1+) lymphomas and possibly a proportion of HD cases, emphasizes the need
      for their diagnostic differentiation from polymorphic "blastic"' cell lymphomas,
      immunoblastic ones in particular.

PMID- 7567164
TI  - [Epidermal infiltration of melanoma].
AB  - The infiltration of the epidermis by malignant melanocytes is a characteristic
      phenomenon of cutaneous melanoma. A series of consecutive unselected cutaneous
      melanomas was histologically reviewed in order to study the frequency and the
      characters of epidermal infiltration. Such a feature was found in 86% of tumors
      (93% in superficial spreading melanomas); it was extensive in 65% of cases, focal
      in 35%; topographically, it was central and peripheral in 67%, peripheral in 30%,
      central in 3%. Results show that epidermal infiltration, albeit inconstant, is a
      useful feature in the histological diagnosis of melanoma (especially in SSM),
      provided that it is distinguished from pseudoinfiltration, a histologically
      similar, but intrinsecally different, feature observed in some benign melanocytic
      lesions.

PMID- 7567165
TI  - [Perisinusoidal stellate cells in a model of experimental liver cirrhosis].
AB  - The association of the common bile duct (CBD) ligation followed by CCl4 and
      progesterone treatment leads to liver cirrhosis in rats in 28 days. The resulting
      cirrhosis shows mixed aspects: it starts as biliary cirrhosis and goes on to
      nodular and periportal pseudolobular form of cirrhosis. Because Ito cells are the
      main source of extracellular matrix components, changing their phenotype from
      quiescent Ito cells to myofibroblast like cells, the purpose of this study was to
      evaluate the behaviour of Ito cells by the immunohistochemistry technique of
      desmin and alpha-SM-actin after these treatments. After CBD ligation alone,
      positive Ito cells for desmin remarkably proliferate around adenomateous areas;
      after treatment with CCl4 alone desmin positive stellate cells are more numerous.
      Desmin positive Ito cells in CBD ligation and CCl4 treatment were even larger
      than those of the previous lots. Significant differences were not observed after
      progesterone and for the alpha-SM-actin positive cells.

PMID- 7567167
TI  - Assessment of proliferating cell nuclear antigen (PCNA) immunoreactivity in
      exocrine pancreatic carcinomas.
AB  - Ten patient with exocrine pancreatic carcinomas were studied
      immunohistochemically, using a monoclonal antibody against PCNA. The percentage
      of tumor cells with positive staining was defined as PCNA Labelling Index (L.I.),
      and ranged from 13.8% to 92.8%. PCNA L.I. was found to correlate significantly
      with grading and more specifically with mitotic activity and degree of nuclear
      anaplasia. No correlation was found with granular differentiation or with vessel
      invasion, lymphatic vessel invasion, lymph node metastasis, perineural invasion
      or size of tumor. Our results indicate that mitotic activity and degree of
      nuclear anaplasia might be the most important parameters to take into
      consideration, when studying the role of PCNA in exocrine pancreatic carcinomas.

PMID- 7567166
TI  - [Clinical usefulness of the immunophenotypic study of circulating lymphocytes in
      leukemic lymphoproliferative diseases].
AB  - The immunophenotypes (IF) on peripheral lymphocytes of 24 B-CLL in different
      stage, 2 PLL and 14 leukemic B-non Hodgkin lymphomas were investigated. As regard
      to B-CLL and PLL, the results are similar to those reported so far. In stage A
      and B of B-CLL the IF appear less variable than in advanced stages where a
      decrease of CD21+ and an increase of both CD25+ and CD38+ lymphocytes were
      observed. In the lymphocytic, small cleaved cell lymphomas and splenic lymphomas,
      the peripheral IF correspond to the theoretical ones of respective lymphoma
      tissues. On the contrary they disagree in three cases of large cells, mixed small
      and cleaved cell, immunoblastic lymphomas. These features are discussed.

PMID- 7567168
TI  - [Inflammatory pseudotumor of the breast. Report of a case and review of the
      literature].
AB  - Inflammatory pseudotumor (IPT) truly represents an enigmatic entity. A tumor-like
      lesion known with many synonyms according to the various patronymic authors who
      named it on the basis of the different observed morphological appearances. Among
      these names plasma cell granuloma, plasma cell/histiocytoma complex, xanthomatous
      pseudotumor, xanthoma, fibrous xanthoma, histiocytoma, xanthogranuloma,
      inflammatory myofibroblastic tumor, inflammatory myofibrohistiocytic
      proliferation are just the most renown. The enigma consists in the fact that it
      can easily be misunderstood as a sarcoma with a marked inflammatory component
      just as reciprocally an inflammatory sarcoma can be misinterpreted as an IPT. As
      it was not enough some authors believe that some so-called IPT actually represent
      or may evolve into a true neoplastic process. For this reason a big debate has
      been raised concerning the biologic behaviour of this entity and a sense of
      scepticism often surrounds pathological diagnoses termed under this rubric. The
      predominant pattern is that of a plasma cell infiltration with a definitely
      histiocytic component and mostly bland spindle shaped cells which occasionally
      can look somewhat atypical, and can form fascicles in some areas. Anyway putting
      apart diagnostic misinterpretations, IPT pathogenetically is intended as the
      result of an inflammatory process mediated locally by an inappropriate production
      of monokines. It has been described in many different anatomic visceral and
      somatic sites, from the classical ones such as soft tissues and retroperitoneum
      to the most unusual such as nervous system and its covering to the most recently
      observed such as skin or lymph nodes or salivary glands. Breast is definitely an
      exoteric site of location of such kind of lesion. Only one case has previously
      been described. This case regards a lady aged 38 years which was locally treated
      by surgical excision: this case aside the standard microscopic examination was
      also studied immunohistochemically including proliferation markers (Ki-67/MIB-1)
      and on flow cytometry which are helpful means to confidently diagnose such
      entity. The differential diagnoses and diagnostic difficulties concerning the
      correct interpretation of this lesion are dealt with.

PMID- 7567169
TI  - [Cerebral amyloid angiopathy (congophilic angiopathy): a rare cause of massive
      cerebral hemorrhage. Report of an "age-related" sporadic case].
AB  - Cerebral amyloidosis is a form of organ-limited amyloidosis, which doesn't
      involve any organ other than brain and which comprises several subtypes,
      including "congophilic angiopathy" (CA), "senile plaques" (SP), "neurofibrillary
      degeneration" (ND), "stellate amyloid cores" of spongiform encephalopathies. It
      is found in 5 to around 20% of human population in people aged 60 to 90 years,
      the increasing being strictly related to ageing. Usually it is associated to SP
      and occasionally to ND, being distinguished into familial and non-familial (age
      related) variants. It affects intracortical and leptomeningeal variously sized
      vessels of the brain and is a leading pathogenetic factor in determining a rare
      but possibly even recurrent form of a massive intraparenchymal cerebral
      hemorrhage, constituting a 0.2 per cent of brain vascular accidents of any origin
      and a 5-10 per cent if only primary non traumatic brain hemorrhages are
      considered. A case of non-familial CA in a previously non-demented nor
      hypertensive female patient aged 65 years is reported on, who was admitted due to
      an almost abrupt onset of neurologic symptoms mainly dominated by a sudden loss
      of consciousness together with a left sensory-motor deficiency syndrome. The
      patient who had been operated on of unilateral mastectomy eight years earlier due
      to an invasive ductal carcinoma of the breast was found affected by a devastating
      brain hemorrhage in the right temporo-occipital lobes with subsequent deflection
      of the brainstem axis toward the opposite side detected by means of CT/MRI and
      angiographic investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567171
TI  - Peculiar meningeal tumour in a 4-months old baby: malignant fibrous histiocytoma?
AB  - The histological examination of a meningioma-like tumour operatively removed from
      the left frontoparetial region of a 4-months-old baby, disclosed a high-cellular
      malignant neoplasia built up by streams of elongated spindle-shaped cells, and
      with a predominant storiform-pattern as usually seen in malignant fibrous
      histiocytoma (MFH). Immunohistochemical reactions for alfa-I-ACT and Lys were
      negative; tumor cells expressed vimentin. Electronmicroscopy disclosed fibroblast
      like cells. This tumour was compared with a recurring malignant fibroblastic
      meningioma characterised, in the recurrence, by storiform areas. In this second
      tumour, alfa-I-ACT was highly positive. Questions concerning the occurrence of
      primary cerebral MFHs are discussed. The immunohistochemical findings in-the
      tumours of the present investigation underline the not-specificity of so-called
      histiocytic markers.

PMID- 7567170
TI  - Solitary extramedullary plasmocytoma of the breast with kappa monoclonal
      gammopathy.
AB  - We report a case of solitary extramedullary plasmocytoma of the breast in a 85
      year old woman. This is the third case of solitary breast plasmocytoma in the
      world's literature. This disorder is very rare and it was associated with a serum
      monoclonal protein. A similar case is presented and its clinical presentation and
      pathology discussed.

PMID- 7567172
TI  - Mitral valve prolapse in a case of Marfan syndrome with congenital cardiac
      disease, chronic obstructive pulmonary disease and schizophrenia.
AB  - Mitral valve prolapse (MVP) is a common pathological finding in several inherited
      connective-tissue diseases among which the Marfan syndrome. In the literature
      several cases of Marfan syndrome characterized by schizophrenia, chronic
      obstructive pulmonary disease and severe mitral regurgitation due to a MVP have
      been reported. Our case of MVP was observed in a patient with Marfan syndrome
      with its characteristic musculoskeletal disorders associated with congenital
      cardiac disease, severe chronic obstructive pulmonary disease and schizophrenia.
      According to the latest genetic studies, Marfan syndrome seems to result from
      genetic mutations in an extracellular matrix glycoprotein, fibrillin. Authors
      believe that MVP represents only one of several pathological alterations which
      may be seen in the Marfan syndrome, as expression of a more generalized genetic
      disorder.

PMID- 7567173
TI  - [Solitary fibrous tumor of the pericardium].
AB  - A 60-year-old man with a large pericardial effusion was found to have a large
      intrapericardial mass located anteriorly to the right ventricle and firmly
      attached to the ascending aorta and pulmonary trunk. Histologically the mass,
      which was completely excised together with its large base of implant, was found
      to be a Solitary Fibrous Tumor. After a 46-months follow-up the patient is free
      from symptoms and signs of recurrence. Solitary Fibrous Tumor is considered a
      benign tumor and its excision curative, however aggressive variants and
      metastasis have been reported. Patternless architecture, fibrous collagenous
      stroma, exclusive vimentin positivity and the lack of ultrastructural mesothelial
      markers are important tools for the diagnosis. Because of the extreme rarity of
      intrapericardial location and lack of information on long-term behaviour of this
      tumor, close non-invasive follow-up is necessary.

PMID- 7567174
TI  - Clear cell carcinoma simulating the "endometrioid-like variant" of yolk sac
      tumor.
AB  - The authors report a case of clear cell carcinoma of the ovary simulating the
      "endometrioid-like variant" of YST only recently described by Clement. The tumor
      was characterized histologically by a villoglandular component intermingled with
      an endometrioid like glandular pattern, nuclear pleomorphism with abnormal
      mitotic figures, eosinophilic hyaline PAS-D resistant bodies and diffuse, typical
      sopranuclear and subnuclear vacuolization according to Clement's description.
      Clinical features as the old age of the patient and laboratory investigations,
      suggested the possibility of a surface epithelial origin of the neoplasia, that
      was substantiated by subsequent additional sections and by immunohistochemical
      staining for AFP, AAT and CEA.

PMID- 7567175
TI  - Desmoplastic malignant melanoma (neurotropic variant).
AB  - A case of neurotropic variant desmoplastic malignant melanoma is reported. The
      report deals with a tumor consisting of dense stroma in which fusiform cells are
      immersed and whose reduced capacity to produce melanin makes correct diagnosis
      difficult in the absence of an associated nevus lesion. Immunohistochemical
      characteristics and possible differential diagnoses are discussed.

PMID- 7567176
TI  - Nodular amyloidosis of the larynx.
AB  - Clinical features of laryngeal amyloidosis may suggest an erroneous diagnosis of
      squamous cell carcinoma. The immunohistochemical findings of monoclonal IgA-kappa
      positive plasma cells, together with kappa chain positive amyloid blocks suggest
      the definition of the present care as a localized plasmacytoma arising in mucosa
      associated lymphoid tissue.

PMID- 7567177
TI  - Hairy cell leukemia without splenomegaly nor myelofibrosis in a patient with
      gastric adenocarcinoma: early phase of the disease or a variant?
AB  - The first case of patient affected both by gastric carcinoma and hairy cell
      leukemia (HCL) is reported. From a clinical standpoint, this 54-year old man
      presented with striking leukopenia without splenomegaly. From a morphological
      point of view, the infiltration by leukemic cells occurred in the hypoplasic
      areas of the bone marrow biopsy (BMB) without increase in reticulin fibers. From
      these observations the authors deduce that: 1) BMB in many cases is the only
      morphologic tool for diagnosis and prognosis of HCL; 2) probably the "hypoplasic"
      variant of HCL will become more frequent, because of the increasing indication to
      BMB in course of pancytopenia, even in absence of splenomegaly; 3) our case is
      probably related more to an early phase of the disease than to a distinct
      variant. In addition, we propose that the co-existence of an aggressive solid
      tumor and HCL could be related to the immunosuppressive action by hairy cells.

PMID- 7567178
TI  - A pediatrician's view. Crib death and managed care.

PMID- 7567179
TI  - SIDS epidemiology and incidence.

PMID- 7567180
TI  - SIDS prevention.
AB  - The mortality attributed to sudden infant death syndrome ahs decreased
      significantly in Northern Europe and Australia in conjunction with the majority
      of infants being placed to sleep on their back or side instead of on their
      stomach. Since the AAP recommendation in 1992 to place healthy infants on their
      back or side to sleep, the fraction of infants sleeping prone in the United
      States has decreased to approximately 43%. It is hoped that the national "Back to
      Sleep" education campaign will accelerate the acceptance of back or side sleeping
      for healthy infants so that only a small fraction of infants will be sleeping on
      their stomach within the next few years. Health-care providers should promote the
      recommendation in the newborn nursery and at well-baby visits. They should
      encourage dialogue with caregivers regarding this and other early infant care
      practices. It is still too soon to know how predominantly nonprone sleeping will
      affect the rate of SIDS in the United States. It is important that providers
      continue to stress access to prenatal and well-baby care, and cessation of
      smoking and substance abuse, as these risk factors may play a larger role in the
      high-risk communities in the United States. Pediatric medical personnel should
      advocate for proper death certification for infants and children, to include
      state legislation that supports autopsies for sudden unexpected deaths in
      children, and the establishment of state child fatality investigation and review
      teams. They also should participate in the training of death scene investigators
      or be part of the death scene investigative team.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7567181
TI  - The postmortem examination.

PMID- 7567182
TI  - Supporting families after sudden infant death.

PMID- 7567183
TI  - Sudden infant death syndrome and brainstem research.

PMID- 7567184
TI  - Bone mineral metabolism in children with juvenile rheumatoid arthritis.
AB  - Osteopenia has emerged as a major determinant of the outcome of children with
      juvenile rheumatoid arthritis. Although vertebral compression fractures and
      fractures of long bones were recognized historically as important clinical
      developments in the course of disease, a decrease in skeletal mass could only be
      quantitated and documented early in disease by the recent introduction of bone
      absorptiometry. This article is limited to recent data from studies on osteopenia
      in juvenile rheumatoid arthritis and suggests directions of future research that
      have relevance to current unanswered questions in prevention or management.

PMID- 7567185
TI  - Physical fitness in children with juvenile rheumatoid arthritis and other chronic
      pediatric illnesses.
AB  - This article discusses the importance of physical fitness and exercise in healthy
      adults and children, and differentiates the terms "physical fitness" and
      "physical activity". The benefits of physical activity for adults and children
      with chronic illnesses and rheumatic diseases are emphasized.

PMID- 7567186
TI  - Spondyloarthropathies of childhood.
AB  - The term spondyloarthropathy, currently used to describe some forms of idiopathic
      arthritis of childhood, may be inappropriate because most children included in
      this category do not have arthritis of the spine, and inflammatory disease of the
      sacroiliac joints is an infrequent or late finding. Juvenile AS, the archetype,
      or "complete" disease may account for only one fifth of the so-called
      "spondyloarthropathies". "Incomplete" or "early" spondyloarthropathies are most
      frequent. Such children may not develop axial symptoms and signs for 5 to 10
      years after onset, and they may be better characterized as having enthesitis
      related arthritis, a term proposed by a recent task force of the International
      League Against Rheumatism (ILAR). Reactive arthritis, although etiologically
      linked with the spondyloarthropathies, uncommonly progresses to AS in childhood;
      most patients have peripheral arthritis with or without enthesitis resolving in
      the relatively short term. The arthritis associated with IBD is more commonly
      peripheral than axial. Although axial disease undoubtedly occurs in JPsA, in the
      authors' experience it is very uncommon.

PMID- 7567187
TI  - Juvenile dermatomyositis. Pathophysiology and disease expression.
AB  - In summary, the child who develops the symptoms of the specific rash, proximal
      muscle weakness, or fatigue should seek medical care promptly. With the advances
      in physical and medical therapy, many of the consequences of the disease can now
      be ameliorated. Data suggest that JDMS and PM may each have a different
      pathophysiology, but more evidence is needed. The next few years will be exciting
      as there is a national effort by an increased number of investigators to
      determine the epidemiologic and genetic factors that influence JDMS disease
      susceptibility and severity.

PMID- 7567188
TI  - Drug treatment in children with juvenile rheumatoid arthritis. Past, present, and
      future.
AB  - Rheumatology made its debut as a legitimate subspecialty of pediatrics sometime
      in the 1940s in Europe, and in the 1970s in North America. Therapy of juvenile
      rheumatoid arthritis has evolved from salicylates and gold injections to newer,
      less toxic nonsteroidal anti-inflammatory drugs and methotrexate. Corticosteroids
      remain as important drugs when life-threatening complications or blinding
      iridocyclitis develop. Immune response modifiers and gene therapies offer
      considerable potential for eventually halting or curing the disease but have yet
      to make a substantial impact on therapy. Methods for the correct conduct and
      interpretation of data from clinical trials are discussed.

PMID- 7567189
TI  - Functional measures in children with rheumatic diseases.
AB  - The measurement of function in children with rheumatic diseases is an intimate
      part of not only the initial diagnostic work-up, but also of every clinic visit
      during the course of these chronic diseases. This article focuses on the
      development of specific and general instruments used to systematically measure
      function and thus, outcome of the rheumatic diseases and their treatments.
      Reference is made to instruments developed for use in the general pediatric and
      adult rheumatology population as a basis for the discussion of the instruments in
      use in pediatric rheumatology. Specifically, the dimensions of physical function,
      psychosocial impact, economic impact and quality of life are addressed.

PMID- 7567190
TI  - Clinical and genetic evidence that juvenile arthritis is not a single disease.
AB  - Ample evidence shows that what was formerly called "juvenile rheumatoid
      arthritis" is not a single disease. At least six separate diseases were included
      as subgroups or subtypes of juvenile rheumatoid arthritis in other
      classifications. The clinical and laboratory features that differentiate these
      diseases are discussed. Genetic differences, primarily within the HLA system but
      also for T-cell receptor genes are described and correlated with the new clinical
      classification of arthritis.

PMID- 7567191
TI  - Scleroderma in children.
AB  - Childhood scleroderma may present in a variety of clinical forms that differ in
      clinical presentation, extracutaneous features, clinical course, and outcome. All
      include hardening of the skin as a major feature. This article reviews these
      various entities, focusing on primarily the clinical features. In addition,
      current concepts regarding pathogenesis and treatment are discussed.

PMID- 7567192
TI  - Kawasaki disease.
AB  - This article is an up-to-date review of issues surrounding Kawasaki disease, with
      particular emphasis on the immunologic aspects. Kawasaki disease is now the
      leading cause of acquired heart disease in children in most developed countries.

PMID- 7567193
TI  - A practical guide to systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a challenging disease with varied manifestations
      resulting from widespread immune complex deposition. It may present in the
      general pediatric office as an acute illness with fever, rash, and hematuria, or
      as chronic fatigue and malaise that might be mistaken for "school phobia".
      Although SLE remains an infrequent disease in general pediatric practice, mild
      cases are more frequent than was previously recognized. These children benefit
      from therapy if the physician is alert to their occurrence and makes the
      appropriate diagnosis. The understanding of the role of genetics and
      environmental agents in the pathogenesis of SLE has improved over the past 10
      years. In addition, the past 10 years have seen refinements in the use of
      immunosuppressive regimens, such as cyclophosphamide, that have led to both
      improved quality of life and improved survival for children with active SLE
      unresponsive to corticosteroids. Although long-term concerns regarding the safety
      and efficacy of immunosuppressive drug regimens persist, the future is
      increasingly bright for children with SLE who receive appropriate care in a
      timely fashion.

PMID- 7567194
TI  - Vasculitis in children.
AB  - Common vasculitic disorders in children include those associated with infections
      (e.g., Rickettsiae, subacute bacterial endocarditis), Schonlein-Henoch purpura,
      and Kawasaki disease. Recent advances have occurred in understanding the
      pathogenesis of vasculitides. In this review, the reader will be exposed to some
      of the developments in adhesion molecules, antineutrophil cytoplasmic antibodies,
      antiendothelial antibodies, and antiphospholipid antibodies. Classification
      criteria and diagnostic strategies are also summarized.

PMID- 7567195
TI  - Rehabilitation of the child with a rheumatic disease.
AB  - This article discusses the principles of rehabilitation of the most common
      childhood rheumatic diseases, especially juvenile rheumatoid arthritis,
      dermatomyositis, and scleroderma. Any rehabilitation program must be undertaken
      in conjunction with understanding of disease processes, appropriate medical
      management, and patient and family education. Investing effort into avoiding
      contractures, weakness, osteoporosis, and disability is considerably less time
      consuming, painful, and costly than trying to reverse established problems.

PMID- 7567197
TI  - You are not alone. Advocacy for children and young adults with rheumatic
      diseases.
AB  - The goal of this article is to assist individuals with an interest in childhood
      rheumatic diseases to gain the knowledge and the skills necessary to become a
      strong advocate for their own, or someone else's, needs. Seeking information and
      help, as demonstrated by Jeremy's mother, shows how rewarding the process of
      becoming an advocate can be.

PMID- 7567196
TI  - The school experience of children with arthritis. Coping in the 1990s and
      transition into adulthood.
AB  - To the arthritic child and his or her family, the pediatrician is a valuable
      resource. When school problems first occur in elementary school, the pediatrician
      can try to solve them with an informal contact with the school teacher, nurse,
      counselor, or principal. If that effort is unsuccessful, the pediatrician can
      then suggest that the family go to the school and request the Individual
      Education Plan (IEP). Although this mechanism is hardly a panacea and local
      school district variability exists, this process provides an opportunity for the
      parent and school personnel to sit down and discuss how the child's problems and
      illness impact school performance. Furthermore, the IEP attempts to adapt the
      school environment specifically for that child. The current mechanism of
      modification of a child's education is the result of a long, evolutionary
      societal and educational process. Educators now recognize that children with
      disabilities and chronic illnesses are entitled to an appropriate public
      education with a special focus on how illness can interfere with that education.
      Whatever congressional changes are likely in the 1990s, many of these civil
      rights advances for the disabled or chronically ill child should survive. The
      transition of the adolescent with a chronic illness, such as arthritis, into
      adulthood has received little attention. This is an area where a compassionate
      and supportive pediatrician may help prevent adolescent problems rather than
      simply reacting to them. A gradual, incremental transition program in the
      pediatric office and clinic may increase the chances that more of these special
      adolescents will become productive, contributing adults.

PMID- 7567198
TI  - Fever of unknown origin.
AB  - The causes of fever in a child can vary from minor brief illnesses to life
      threatening infectious, malignant, or autoimmune diseases. The physician often
      has to evaluate children with fevers of as yet undiagnosed cause lasting fewer
      than 2 weeks, in whom it is important to determine whether localizing findings
      are present. Fever without localizing signs and fevers complicating chronic
      disease and resulting from specific localized infection are considered in the
      sections concerning infectious causes, immunodeficiency diseases, and rheumatic
      diseases. The diagnostic and therapeutic approaches to the child with both
      prolonged fever and fever of unknown origin are then discussed, with emphasis on
      rheumatic diseases.

PMID- 7567200
TI  - The use of capnography for recognition of esophageal intubation in the neonatal
      intensive care unit.
AB  - Failure to recognize esophageal intubation can result in severe hypoxia and
      permanent neurologic injury. Capnography is a standard monitoring modality in the
      operating room but has not been utilized fully in other environments. We used
      capnography at the time of endotracheal intubation in the neonatal intensive care
      unit (NICU) to determine whether capnography could more quickly and accurately
      identify endotracheal tube position than other clinical indicators of
      endotracheal tube position. One hundred intubation episodes were studied in 55
      neonates. Capnograms were obtained 15 and 120 sec following tube placement.
      Intubating personnel were blinded to the capnographic data and determined
      endotracheal tube location (trachea vs. esophagus) by clinical criteria only. The
      sensitivity and specificity of capnography and clinical examination for
      identification of tube position were analyzed, and the time required for
      establishing by clinical confirmation whether the tube was in the trachea or not
      was compared to that required for capnography. Forty of 100 intubation attempts
      resulted in esophageal intubation. Capnography correctly identified these errant
      tube placements in 39 of 40 instances and did so in 1.6 sec (SD +/- 2.4).
      Capnography failed to identify successful endotracheal intubation on only one
      occasion. Clinical indicators of tube position required 97.1 sec (SD +/- 92.6) to
      identify an esophageal intubation and failed to identify successful endotracheal
      intubation in 5 of 60 cases. We conclude that capnography is a valuable adjunct
      to clinical examination to demonstrate whether an endotracheal tube is placed
      correctly in the trachea of neonates in the NICU.

PMID- 7567199
TI  - Vitamin A status and airway infection in mechanically ventilated very-low-birth
      weight neonates.
AB  - Vitamin A (retinol) plays an important role in immunity. Respiratory and enteral
      infections in children are associated with low serum vitamin A concentrations
      that improve during recovery. To test the hypothesis that airway infection in
      very-low-birth-weight (VLBW) neonates likewise may be associated with a change in
      vitamin A status, we examined 20 VLBW neonates (selection criteria: birth weight
      700-1300 g, gestational age 26-30 weeks, need for supplemental oxygen and
      mechanical ventilation for > 72 hr after birth) who were enrolled in the control
      group of a randomized clinical trial of vitamin A supplementation reported
      earlier. We studied changes in weekly measurements of plasma concentrations of
      vitamin A and retinol-binding protein (RBP) during 4 weeks following enrollment
      in the trial (postnatal day 4) and compared changes between periods with and
      without airway infections. Seventeen infants had 22 episodes of documented airway
      infection. Staphylococcus epidermidis was the predominant organism. Plasma
      vitamin A concentrations decreased during 19 out of 22. With airway infection
      (mean change: -4.1 to -18.6 micrograms/dL), while they increased during 37 out of
      58 periods without airway infection (mean change: -0.2 to +5.8 micrograms/dl; P <
      0.001). The mean (+/- SD) plasma vitamin A concentrations before, during, 1 week
      after, and 2 weeks after an episode of airway infection were 20.9 +/- 8.3, 9.7 +/
      4.1, 12.8 +/- 8.9, and 16.2 +/- 7.2 micrograms/dL, respectively. The mean value
      during airway infection was significantly lower than those before and two weeks
      after airway infection (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567201
TI  - Does continuous positive airway pressure (CPAP) during weaning from intermittent
      mandatory ventilation in very low birth weight infants have risks or benefits? A
      controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate three ventilator weaning
      strategies and to evaluate whether the use of continuous positive airway pressure
      (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of
      extubation failure in very low birth weight (VLBW) infants. STUDY DESIGN: We
      studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188
      g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned
      from intermittent mandatory ventilation (IMV). Infants were assigned by
      systematic sampling to one of the following three treatment groups: (1) direct
      extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET
      CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP)
      for 12-24 hr (n = 29). Failure was defined as the need for resumption of
      mechanical ventilation within 72 hr of extubation due to frequent or severe apnea
      and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for
      oxygen FiO2 > 60%). RESULTS: There were no significant differences in failure
      rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in
      ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2,
      PaO2, and respiratory rates before and after discontinuation of IMV among the
      three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr
      after weaning from IMV. CONCLUSION: We were unable to demonstrate a clear
      difference in extubation outcome by use of CPAP administered via an endotracheal
      or nasopharyngeal tube when compared to direct extubation from low-rate IMV in
      VLBW infants.

PMID- 7567202
TI  - Tracheal stenting improves airway mechanics in infants with
      tracheobronchomalacia.
AB  - The compliance and expiratory resistance of the tracheobronchial tree is
      increased in infants with tracheobronchomalacia because of a weakness in
      cartilaginous support of the airway. Life threatening episodes may occur in these
      patients due to airway collapse. The goals of this study were to compare the
      effects on respiratory system mechanics of stenting the airway with either
      continuous positive airway pressure (CPAP) or a long tracheostomy tube. Five
      infants were studied: two had bronchopulmonary dysplasia (BPD), 2 had associated
      congenital anomalies, and one had tracheomalacia and polydactyly; none had a
      tracheoesophageal fistula. All patients required tracheostomy and were treated
      with CPAP. Lung mechanics were evaluated by measuring transpulmonary pressure,
      obtained by subtracting airway opening pressure from pleural pressure measured
      with an esophageal balloon, and flow measured with a pneumotachometer placed in
      series with the tracheostomy. Dynamic compliance (Cdyn) and total respiratory
      system resistance (Rt) were calculated by two-factor, least-mean-squares
      analysis, solving for the equation of motion of the lung with the PeDS system
      (MAS, Hatfield). In all subjects Cdyn increased and Rt decreased with increasing
      CPAP. In 4 subjects the airway was stented with a specially designed, long
      tracheostomy tube which reached to just above the carina; the special tube
      improved dynamic mechanics sufficiently to permit the discontinuation of CPAP.
      Speech was improved by fenestrating the tube and the use of a one-way inspiratory
      valve, placed over the tracheostomy. Inspiration occurred via the tracheostomy
      and expiration was directed to the larynx.

PMID- 7567203
TI  - Functional residual capacity (FRC) measurements by plethysmography and helium
      dilution in normal infants.
AB  - Comparative measurements of functional residual capacity (FRC) made by
      plethysmography (FRCpleth) and by helium dilution (FRCHe) were obtained on 27
      infants and young children without known pulmonary disease (14 males, 13 females;
      4 weeks-26 months; mean age 32.2 weeks) while under chloral hydrate sedation.
      Clinical histories, clinical examinations, and pulmonary functions were normal
      for all members of the group. FRCpleth, whether measured near end expiration (EE)
      or near end inspiration (EI), and corrected to mean expiratory levels of at least
      3 breathing cycles, was consistently and significantly greater than FRCHe.
      Comparative values for mean (+/- standard deviation) were FRCpleth EE, 182.0 (+/-
      79.7) mL and FRCpleth El, 171.8 (+/- 77.4) mL vs. FRCHe, 154 (+/- 72.2) mL, P <
      0.0001 and P < 0.005, respectively. Normalizing values by weight, FRCpleth EE was
      23.8 mL/kg (+/- 5.3) vs. FRCHe, 20.2 (+/- 4.7) mL/kg, mean (+/- standard
      deviation). The difference between FRCpleth and FRCHe, expressed as FRCpleth -
      FRCHe/FRCpleth x 100, was 9% for occlusions at end inspiration and 16% for
      occlusions at end expiration. The following equations describe our FRC results in
      relation to length: In (FRCHe) = 2.74 x ln (length) - 6.53 r2 = 0.781 slope =
      2.74 +/- 0.29 SE Y intercept = 6.53 +/- 1.12 SE ln (FRCPleth EI) = 2.69 x ln
      (length) - 6.21 r2 = 0.752 slope = 2.69 +/- 0.31 SE Y intercept = 6.21 +/- 1.29
      SE The difference between FRCpleth and FRCHe was more marked when occlusions were
      performed at end expiration than at end inspiration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7567204
TI  - Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of
      newborn infants: a preliminary report.
AB  - In acute hypoxemic respiratory failure of term and near-term neonates, extra- and
      intrapulmonary right-to-left shunting contribute to refractory hypoxemia. Inhaled
      nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation
      perfusion mismatch in a variety of animal models and selected human patients. We
      report on 10 consecutive term and near-term newborns with severe acute hypoxemic
      respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome,
      group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome,
      who received increasing doses of inhaled NO (up to 80 ppm) to improve the
      arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO
      concentration which improved PaO2 varied considerably between patients.
      Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns
      with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic
      hernia, while in the other 5 patients inhaled NO increased the mean (+/- SE) PaO2
      from 41 +/- 6 to 57 +/- 9 mm Hg (P < 0.05). Optimum NO concentrations determined
      by dose-response measurements performed during the first 8 hr of NO inhalation
      were 8-16 ppm except for 2 newborns with congenital diaphragmatic hernia who
      required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the
      PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time
      (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration
      dropped to less than 3 ppm after prolonged mechanical ventilation or when
      intravenous prostacyclin was given concomitantly.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7567205
TI  - The single breath test in neonates: does pressurization of the pneumotachograph
      make a difference?
AB  - The single breath test for the measurement of respiratory system resistance and
      compliance in newborns consists of an end inspiratory occlusion which is
      subsequently released, allowing expiration to proceed through a pneumotachograph
      (PNT). The measured flow is then integrated to give volume. The simplicity of the
      test is one of the major reasons for its popularity. However, some investigators
      have cautioned against the use of an occlusion distal to the PNT because
      pressurization of the PNT may introduce artifacts in the flow measurement.
      Despite this caution, many commercial systems use a pressurized PNT. This study
      investigated the errors that would result from pressurization of the PNT by
      providing a step function of flow to two infant PNTs, a Fleisch #0 and a Hans
      Rudolph 4500, in the unpressurized and pressurized state. In each case there was
      an initial rapid rise of the flow signal, followed by some overshoot and
      oscillations that rapidly died out. The overshoot and oscillations for the Hans
      Rudolph PNT were greater when pressurized whereas pressurization had little
      effect on the Fleisch PNT. Unpressurized, the two were similar. In either case,
      the artifact introduced by pressurization of the PNT died out so quickly that it
      would have little effect on any measurement in an infant.

PMID- 7567206
TI  - A computer algorithm for differentiating valid from distorted pulse oximeter
      waveforms in neonates.
AB  - Current pulse oximeter technology is fraught with a significant false alarm rate.
      This is mainly due to motion artifacts at the sensor site which distort the pulse
      waveform and render the computation of SaO2 invalid. If the pulse waveform could
      be automatically recognized as either normal or distorted, then only valid SaO2
      values would be displayed. We observed that the systolic upstroke time (Sy) of
      the pulse waveform has a narrow and consistent range in normal appearing pulses.
      The systolic upstroke time (Sy) is the time from the onset of systole to the peak
      of the pulse waveform. Comparison of a preset range of Sy was made against Sy
      obtained by computer analysis of each pulse waveform. Visual examination of
      14,090 pulses was carried out to determine the sensitivity and false positive
      rate of the algorithm. Sensitivity of computer detection of valid pulses was 92%
      with a positive predictive value of 92%. When used on line for continuous
      recording of SaO2 in patients, this simple algorithm has the potential to
      decrease the false alarm rate of pulse oximeters and improve the accuracy of long
      term SaO2 recordings.

PMID- 7567207
TI  - Diaphragmatic flutter in three babies with bronchopulmonary dysplasia and
      respiratory syncytial virus bronchiolitis.
AB  - Abnormalities of respiratory control, especially apnea, have been reported
      previously in infants with respiratory syncytial virus (RSV) infections. This is
      the first report of yet another abnormality of respiratory control, diaphragmatic
      flutter (DF), in infants with RSV infection. The presentation of these infants
      did not differ from the usual clinical presentation of RSV infection. While being
      monitored with respiratory inductive plethysmography for occurrences of apnea
      known to be common in RSV infection, DF was detected. This abnormality consisted
      of high frequency, diaphragmatic contractions which were intermittent in nature.
      They lasted no more than 4 days and were not associated with change in arterial
      oxygen saturation or heart rate. These infants were discharged free of DF and no
      further episodes have been observed over a 12-month period.

PMID- 7567209
TI  - Cold dry air challenge for measuring bronchial responsiveness--where do we stand?

PMID- 7567208
TI  - Syringomyelia and chiari malformation presenting as scoliosis in cystic fibrosis.

PMID- 7567210
TI  - Comparison of airway reactivity induced by cold air and metacholine challenges in
      asthmatic children.
AB  - Bronchial responsiveness to isocapnic hyperventilation with cold air (CAH) and to
      inhaled methacholine (MCH) was compared in 17 children with bronchial asthma. The
      response to cold air was expressed as the percent drop in FEV1 from baseline at 4
      min. after the challenge (delta % FEV1 CAH), and the response to methacholine as
      the provocative concentration required to reduce the FEV1 by 20% from baseline
      (PC20MCH). Both tests were sensitive (94%) for detecting airway hyperreactivity.
      There was no statistically significant relationship between delta % FEV1 CAH and
      the log PC20MCH (r = 0.39; P = 0.12). In clinical practice, methacholine test is
      easier to perform, but in the research field cold air challenge may be preferable
      because it avoids potential drug effects.

PMID- 7567211
TI  - The cost of childhood asthma to Australian families.
AB  - There have been no estimates of the actual cost of asthma care to Australian
      families. Previous estimates have been of the total cost to the community and
      have relied upon data collected by government departments and agencies. It was
      the aim of this investigation to estimate the cost of childhood asthma from the
      parents perspective in Australian families. A total of 238 asthmatic children
      aged 8-12 years were identified through prevalence studies of asthma in Sydney
      and Belmont, N.S.W. Children were selected if they had wheezed in the previous 12
      months, had used asthma medicines or had airway hyperresponsiveness when tested.
      The study sample had a wide range of asthma severity. Data were collected
      retrospectively and prospectively. Parents completed a questionnaire which asked
      about health insurance and special asthma equipment costs in the previous 12
      months. Every 2 weeks for a total of 3 months between February and June parents
      completed further questionnaires which assessed costs incurred because of their
      child's asthma, together with time spent obtaining treatment. Items included
      doctor consultations and tests, alternative practitioner consultations and tests,
      medications and alternative therapies purchased, hospital and ambulance use, and
      the cost of childcare as a consequence of asthma. We collected two or more months
      of prospective data from a total of 193 children. The mean annual cost of asthma
      to the family was A$212.48 per asthmatic child and 13.4 hr were spent obtaining
      treatment. For the group of children who had not visited a doctor in the previous
      year, the mean annual cost was A$85.60 and 13.1 hr were spent obtaining
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567212
TI  - Tryptase immunoreactive mast cell hyperplasia in bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD), the most common cause of chronic lung disease
      in prematurely born infants, is histologically characterized by various degrees
      of airway and alveolar septal fibrosis. Tryptase, a serine protease specific to
      mast cells, has been shown to have potent fibroblast mitogenic properties and in
      addition has been shown to be increased in adult fibrotic lung disorders. Based
      on this analogy, the distribution of pulmonary mast cells exhibiting tryptase
      immunoreactivity was investigated by immunoperoxidase staining in autopsy
      specimens of infants dying with BPD. Morphologically normal lung specimens from
      similarly aged infants dying of sudden infant death syndrome (SIDS) served as
      controls. Tryptase-positive mast cell counts were performed at 250x from at least
      10 random fields in bronchial, peribronchiolar, and alveolar regions. Compared to
      controls, in lung sections exhibiting typical histologic features of long
      standing BPD, tryptase positive cells were significantly increased in bronchial
      (23.9 +/- 3.6 vs 14.4 +/- 2.3) and peribronchiolar (15.3 +/- 3.2 vs 4.63 +/- 0.6)
      regions compared to controls (P < 0.05, Student's t test). In particular,
      alveolar regions exhibiting moderate to severe degrees of septal fibrosis
      exhibited a dramatic increase in the number of tryptase-positive cells (9.83 +/-
      1.89 vs 0.34 +/- 0.18, P = 0.003). These findings of a tryptase-positive mast
      cell hyperplasia in BPD suggest potential roles of mast cells as well as tryptase
      in the pathogenesis of this disease.

PMID- 7567213
TI  - Bronchial artery embolization in the management of hemoptysis in cystic fibrosis.
AB  - Massive hemoptysis and/or recurrent expectoration of measurable amounts of blood
      are common complications of chronic bronchopulmonary infections in cystic
      fibrosis (CF). When conservative treatment fails to control bleeding, surgery or
      bronchial artery embolization (BAE) is frequently considered. We present our
      experience and long-term follow up of BAE in 14 CF patients (age range 15-39
      years) with massive (6 subjects) and/or recurrent (8 subjects) hemoptysis not
      responsive to medical treatment. Seven had chronic hypercapnic respiratory
      failure. After angiographic evaluation, polyvinyl alcohol particles (Ivalon) were
      injected to embolize obviously enlarged bronchial arteries. Seventeen procedures
      were performed in 14 patients and 36 bronchial arteries were embolized. All the
      patients stopped bleeding immediately upon BAE. Most of the patients had
      postembolization fever, dysphagia, and transient chest pain which were managed
      symptomatically. After a median follow-up period of 10.5 months (range 0.5-38
      months), no recurrence of hemoptysis was observed in 8 patients who are still
      alive. In 3 patients hemoptysis recurred and they underwent reembolization after
      3, 22, and 25 months, respectively. Three subjects died of respiratory failure
      within 5 months from BAE. Presently, 50% of patients studied had a > or = 1 year
      interval free of major hemoptysis after the first BAE. Our experience indicates
      that massive and/or recurrent hemoptysis in CF patients can be safety and
      effectively managed by BAE if the procedure is performed by a skilled
      practitioner. The procedure was well tolerated and resulted in prolonged and
      satisfactory bleeding control in most patients.

PMID- 7567214
TI  - Lung sounds in neonates with and without an added dead space.
AB  - Previous studies have reported great difficulty in recording lung sounds from
      neonates and have found conflicting results. We studied lung sounds in neonates
      during the inspiratory phase of the respiratory cycle as monitored by inductive
      plethysmography (A) and by a pneumotachograph and a face mask (B) which added a
      dead space of 12 mL. Sixteen term babies were tested 12 hr to 6 days (median 45
      hours) after birth. Lung sounds were recorded and then analysed using overlapping
      and non-overlapping fast Fourier transforms. The two methods of analysis showed a
      difference in intensity but not in frequency. Fourteen babies provided enough
      breaths for comparison; a total of 596 inspirations were analysed. The intensity
      of lung sounds on occasion B was higher in all but two babies with a mean B/A
      ratio of 2.4. The mean (SD) power on occasions A and B was 13.9 (8.5) mW and 26.9
      (21.0) mW, P = 0.02, respectively. In all but 4 babies the B/A ratios of the
      median (f50) and 90th centile (f90) frequencies were scattered randomly within
      20% of unity. The mean (SD) f50 on occasions A and B was 205.5 (51.1) Hz and
      225.8 (32.3) Hz, P = 0.10, respectively; the mean f90 was 370.3 (91.0) Hz and
      396.1 (67.8) Hz, P = 0.25, respectively. Linear regression showed that there is a
      third-order polynomial relationship between sound intensity and air flow at the
      mouth. A weaker positive association exists between frequency and air flow,
      showing that the median and 90th centile frequencies approach an asymptote as
      flow increases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567215
TI  - A cotton rat model of effectors of immunity to respiratory syncytial virus other
      than serum antibody.
AB  - A model for studying effectors of immunity to respiratory syncytial virus (RSV)
      was developed. Paris of inbred cotton rats (Sigmodon hispidus) were joined
      surgically using the technique of parabiosis. One week later, one animal of each
      pair was primed intranasally with a small volume of RSV suspension. Fourteen days
      after priming, both animals of each pair were bled for determination of serum
      neutralizing antibody titers, and challenged intranasally with a standard dose of
      RSV suspension. Single, unprimed cotton rats were challenged concomitantly and
      served as controls. Four days after challenge, all animals were sacrificed for
      virus titration of nasal tissues and lungs. Parabiosed cotton rats were
      surgically separated at varying intervals between priming and challenge (days 7,
      9, 12, or 14 after priming) or were kept joined until sacrificed (day 18).
      Significant transfer of nasal and pulmonary immunity from primed to unprimed
      parabionts began 9 days after priming, gradually increasing through 18 days.
      Resistance to RSV challenge in spite of low levels of serum neutralizing antibody
      suggests that non-antibody immunologic mediators were responsible for the
      transferred immunity. Evidence is presented for three broad categories of RSV
      immunologic effectors: systemic, local with a transient systemic phase, and local
      without a systemic phase. These categories are now amenable to further study
      using the described model.

PMID- 7567217
TI  - Effects of streptozotocin-induced diabetes on postpneumonectomy lung growth and
      connective tissue levels.
AB  - Diabetes is generally accompanied by abnormal levels of growth hormone and
      adrenal steroids, hormones known to modulate postpneumonectomy (post-PNX)
      compensatory lung growth. Thus, we examined the possibility that diabetes may
      affect post-PNX lung growth processes. Left PNX was performed in young diabetic
      rats (streptozotocin-induced; 75 mg/kg body weight) (DM-PNX) and in control rats
      (C-PNX), for comparison with sham-operated control rats (C-SHAM). The rats were
      permitted free access to food and water. Examination at day 7 after surgery
      showed that right lung absolute dry weight and absolute DNA, collagen and elastin
      contents were increased in C-PNX and DM-PNX rats (but only C-PNX values reached
      those of both lungs in C-SHAM rats). Body weights (BW) of DM-PNX rats were lower
      than those of C-PNX and C-SHAM rats. Lung DNA/BW in C-PNX and DM-PNX rats were
      comparable, and matched values for both lungs in C-SHAM rats. Lung dry weight/BW,
      collagen/BW, and elastin/BW in DM-PNX rats exceeded values in C-PNX rats and even
      more for values of both lungs in C-SHAM rats. Data of another experiment,
      comparing DM-PNX rats with body weight-matched (by food limitation) PNX and
      control rats (WMC-PNX and WMC-SHAM rats, respectively) indicated comparable lung
      absolute DNA contents in DM-PNX and WMC-PNX rats (which matched values for both
      lungs in WMC-SHAM rats), however, lung absolute collagen and elastic contents
      were greater in the DM-PNX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567216
TI  - Intratracheal administration of phosphodiesterase III inhibitor attenuates
      bronchoconstriction in cats: a preliminary report.
AB  - The effects of intratracheal administration of MKS 492, a selective
      phosphodiesterase (PDE) III inhibitor, were studied in five anesthetized
      bronchoconstricted cats. The animals were challenged by four repeated doses of
      intratracheal methacholine (67 micrograms/kg), and the degree of
      bronchoconstriction was assessed from increases in respiratory system resistance
      (Rrs). All animals demonstrated good bronchoconstrictive responses (i.e., 86-99%
      increases in Rrs) to methacholine without tachyphylaxis. On a separate day, the
      cats received the same four doses of methacholine after being pretreated with
      either intratracheal saline or three different doses of MKS 492 (0.17, 1.7, and
      17 micrograms/kg). The increases in Rrs with 1.7 micrograms/kg [52.6 +/- 8.4%
      (SE)] and 17 micrograms/kg of MKS 492 (44.4 +/- 10.1%) were smaller than those
      with saline pretreatment (88.1 +/- 16.8%) (P < 0.05). There were no treatment
      associated changes in mean arterial pressure or heart rate during administration
      of MKS 492. We conclude that intratracheal MKS 492 effectively reduced
      methacholine-induced bronchoconstriction in a dose-dependent fashion without
      substantial systemic effects. These preliminary results suggest that inhalation
      of isozyme-selective PDE inhibitors may deserve consideration for clinical trials
      provided that more extensive preclinical investigations justify such trials.

PMID- 7567218
TI  - The role of inflammation in the pathogenesis of bronchopulmonary dysplasia.

PMID- 7567219
TI  - Interrelationship between postocclusional oscillatory pressure transients and
      standard lung function in healthy and asthmatic children.
AB  - We studied the correlation between characteristics of the postocclusional
      oscillatory airway opening pressure transients after flow interruption and body
      height, the degree of pulmonary hyperinflation [measured by thoracic gas volume
      (TGV)], and the degree of airway obstruction [measured by airway resistance
      (Raw)] and maximal expiratory flow at 50% vital capacity (MEF50) in 10 healthy
      and 50 asthmatic children age 7-16 years. Focusing on the damped oscillatory
      change in pressure, the first derivative of the shutter curve was analyzed,
      featuring a natural frequency fO and damping factor d in the time domain, and
      frequency FFS and power AFS in the frequency domain. A maximal frequency was
      found at approximately 80 Hz without a two peak distribution as described in
      dogs. Multiple linear forward step analysis revealed that omega O (the undamped,
      natural frequency) and AFS were related to body height (P < 0.001). The damping
      factor d (independent of body height) was related to TGV and MEF50 (P < 0.001),
      and FFS to Raw (P < 0.001). The analysis of the postocclusional pressure
      transients after airflow interruption provides information on the resistive,
      elastic and inertive properties of the thoraco-pulmonary system. The measurements
      obtained are influenced by the end-expiratory resting level (or the degree of
      pulmonary hyperinflation) and the degree of airway obstruction.

PMID- 7567220
TI  - Coexistence of hydatid and foregut cysts in the lung: a diagnostic problem.

PMID- 7567222
TI  - Symptomatic increase in intracranial pressure following pancreatic enzyme
      replacement therapy for cystic fibrosis.
AB  - A newly diagnosed 5-month-old infant with cystic fibrosis (CF) developed signs
      and symptoms of increased intracranial pressure (ICP) within days of starting
      pancreatic enzyme replacement therapy. Symptoms promptly resolved on two
      occasions after stopping enzyme replacement. At 10 months of age, enzyme
      replacement was well tolerated.

PMID- 7567221
TI  - A case of influenza virus bronchiolitis complicated by pneumomediastinum and
      subcutaneous emphysema.

PMID- 7567223
TI  - Legionnella pulmonary infection in children on steroids.

PMID- 7567224
TI  - MR and CT imaging patterns in post-varicella encephalitis.
AB  - The aim of the investigation was to determine the patterns of cerebral
      involvement on computed tomography (CT) and magnetic resonance (MR) imaging in
      post-varicella encephalitis. Four children between the ages of 2 and 11 years
      presented over a 5-year period with a diagnosis of post-varicella encephalitis.
      Their imaging studies and clinical data were reviewed retrospectively. The
      medical histories of all four children were noncontributory except for recent
      bouts of chickenpox 1 week to 3 months prior to hospitalization. Three children
      presented with parkinsonian manifestations. Bilateral, symmetric hypodense,
      nonenhancing basal ganglia lesions were found on CT. These areas showed
      nonenhancing low signal intensity on T1-weighted images and high signal intensity
      on T2-weighted images on MR. One child presented with diffuse, multiple gray and
      white matter lesions of similar imaging characteristics; some lesions, however,
      did enhance. This child had no gait disturbances. Post-varicella encephalitis can
      produce two patterns of dramatic CT and MR findings. With an appropriate history
      and clinical findings, varicella as a cause of bilateral basal ganglia or diffuse
      cerebral lesions can be differentiated from other possible etiologies which
      include trauma, anoxia, metabolic disorders and demyelinating diseases.

PMID- 7567225
TI  - The pineal gland: a comparative MR imaging study in children and adults with
      respect to normal anatomical variations and pineal cysts.
AB  - This study was undertaken to evaluate the variations in appearance of the normal
      pineal gland. The findings of 1000 consecutive MR imaging examinations obtained
      at 0.5 T were studied. The age of the patients ranged from 1 day to 83 years, and
      findings in children and adults were compared. In all age groups the pineal gland
      appeared mainly in three forms: (1) nodule-like, (2) crescent-like and (3) ring
      like. Overall prevalences of these forms were 52%, 26% and 22%, respectively.
      Apparent differences in frequencies were evident in children and adults with
      respect to the crescent- and ring-like types. Cystiform pineal lesions 5 mm or
      larger in one diameter (anteroposterior, sagittal or transverse) were taken to be
      true pineal cysts, when compared with the gland's ring-like appearance (less than
      5 mm). Pineal cysts had a prevalence of 0.6% in children and 2.6% in adults. No
      symptomatic pineal cyst with mass effect on the lamina tecti was detected in the
      series. Besides identifying the three anatomical types of the pineal gland as
      seen on MR imaging and addressing the potential significance of differences in
      their frequencies in children and adults, the author tries to explain the
      previous discrepancy between the MR imaging and autopsy series findings with
      respect to frequencies of the pineal cysts.

PMID- 7567226
TI  - MR and CT diagnosis of carotid pseudoaneurysm in children following surgical
      resection of craniopharyngioma.
AB  - We report the cases of two children who underwent CT, MR, MRA and angiography in
      the diagnosis of postoperative aneurysmal dilatation of the supraclinoid carotid
      arteries following surgical resection of craniopharyngioma. Craniopharyngiomas
      are relatively common lesions, accounting for 6-7% of brain tumors in children.
      They are histologically benign, causing symptoms by their growth within the sella
      and suprasellar cistern with compression of adjacent structures, especially the
      pituitary gland, hypothalamus and optic nerves, chiasm, and tracts. Complete
      surgical resection, particularly of large tumors, is complicated by the fact that
      the lesions are usually found within the circle of Willis, with displacement and
      adherence to the adventitia of these vessels [1, 2]. Recent reports in the
      neurosurgical literature have described aneurysmal dilatation of the supraclinoid
      internal carotid arteries following aggressive surgical resection of
      craniopharyngioma [3, 4].

PMID- 7567227
TI  - Association of idiopathic hypopituitarism and syringomyelia.
AB  - The magnetic resonance in an 8-year-old boy with hypopituitarism and cervical
      syringomyelia are presented. Magnetic resonance imaging of the brain clearly
      demonstrated syringomyelia in the cervical spinal cord and transection of the
      pituitary stalk, findings identical to those reported in the literature. Both
      disorders have been seen in association with a difficult labor, so we suggest
      that this is not a chance finding.

PMID- 7567229
TI  - Adrenoleukodystrophy: CT and MRI findings.
AB  - A case of adrenoleukodystrophy (ALD) with CT and MRI findings is described. The
      CT scan showed low densities in the white matter of the parietal and occipital
      lobes. No calcifications were seen. Post-contrast CT showed an abnormal
      enhancement within the involved white matter. MRI showed changes of demyelination
      around the atria of the lateral ventricles bilaterally involving the posterior
      aspect of the cerebrum symmetrically. The posterior part of the posterior corpus
      callosum, splenium and pyramidal tracts also showed increased signal intensity.
      From a review of the literature, these findings are typical of the radiological
      changes seen in ALD. ALD can be diagnosed from typical history and biochemical
      changes as well as from CT and MRI findings.

PMID- 7567228
TI  - Subependymal germinolytic cysts in Zellweger syndrome.
AB  - Ultrasonographic demonstration of periventricular cysts is usually associated
      with cystic periventricular leucomalacia due to necrosis of periventricular
      unmyelinated white matter. Cystic spaces with a similar appearance may also arise
      from prenatal lysis of fetal periventricular matrix tissue, rather than immature
      white matter. The resultant empty spaces are called "pseudocysts" or germinolytic
      cysts. Neuropathological studies have shown that germinolytic cysts may arise in
      Zellweger syndrome (generalized peroxisomal disorder). Here, we report their
      ultrasonographic demonstration in Zellweger syndrome, emphasizing the potential
      value of this sign in the diagnosis.

PMID- 7567231
TI  - Posttraumatic diaphragmatic herniation: CT findings in two children.
AB  - Traumatic diaphragmatic hernia is a rare injury in children. The diagnosis is
      often delayed because of nonspecific clinical and radiologic findings. We report
      the CT findings in two children with visceral herniations, one hepatic and one
      gastric, resulting from traumatic rupture of the diaphragm. Motor-vehicle
      accidents are the most common cause of acquired diaphragmatic hernia in children
      [1]. Because it is rare and often overshadowed by associated injuries, the
      diagnosis of posttraumatic diaphragmatic rupture is often delayed [1, 2]. We show
      how CT can aid visualization of the diaphragm or reveal associated findings
      leading to the diagnosis of diaphragmatic rupture.

PMID- 7567230
TI  - Midgut malfixation in patients with congenital diaphragmatic hernia: what is the
      risk of midgut volvulus?
AB  - Twenty-four patients with repaired diaphragmatic hernia had upper
      gastrointestinal series to assess the rotation and fixation of the bowel. A
      spectrum of rotational abnormalities was present in almost all patients, although
      those with repaired right-sided hernias demonstrated a more obvious anomaly of
      rotation than those with repaired left-sided hernias. No patient developed a
      midgut volvulus despite the presence of malfixation. Postoperative adhesions
      likely limit the occurrence of volvulus.

PMID- 7567232
TI  - Anomalous inferior vena cava in association with omphalocele: a case report.
AB  - We present the case of a 6-year-old boy who had an omphalocele repaired at day 1
      of life. He had a secundum atrial septal defect and an anomalous inferior vena
      cava of a type which has not been previously reported. Cine-MRI was a useful
      noninvasive tool for diagnosing the anomalous subaortic innominate vein and four
      immature vessels which make up the venous drainage systems of the lumbar region.
      The recognition of this malformation is important in planning and executing
      surgical repair or cardiac catheterization for postoperative patients with
      omphaloceles.

PMID- 7567233
TI  - Tailoring the small-bowel follow-through examination postoperatively in
      gastroschisis patients.
AB  - The purpose of this paper is to establish a small-bowel follow-through (SBFT)
      protocol in post-operative gastroschisis patients. In 15 years, 19 SBFT
      examinations have been performed to diagnose or exclude obstruction in 61
      gastroschisis patients. The average examination required 6.7 overhead films
      (range 3-15) and lasted 34 h (1-190 h). The diagnosis of intestinal obstruction
      was supported on SBFT in only 1 of 19 patients who underwent this examination. In
      the other 18, the examination showed no obstruction (13 patients) or was
      nonconclusive (5 patients). The inherent dysmotility associated with
      gastroschisis can result in redundant overhead films being made during SFBT. We
      recommend that an SBFT examination in gastroschisis patients consist of (1)
      fluoro-evaluation of esophagus, stomach, and duodenum; (2a) if normal peristalsis
      is noted, then an overhead film at 30 min, or (2b), if altered peristalsis or
      little movement of contrast medium is noted on the 30-min overhead film, then an
      overhead film at 4 and 12 h. This is followed by overhead films every 24 h if
      required. This protocol can result in a decrease in patient radiation, department
      costs, and staff work load.

PMID- 7567234
TI  - Complex colon duplication mimicking an obstructed, non-functioning kidney in a
      newborn with imperforate anus and spinal dysraphism.
AB  - Gastrointestinal (GI) duplications contain tissue resembling several portions of
      the GI tract and are associated with vertebral and genitourinary (GU)
      abnormalities [1-4]. We report a newborn with low, imperforate anus and
      lumbosacral dysraphism, who presented with a large cystic mass in the left renal
      fossa and pelvis. The flank mass (felt initially to be a dysplastic kidney and
      ureter) proved to be a complex GI duplication with histologic evidence of
      gastric, small bowel, and colonic mucosa, as well as respiratory epithelium and
      pancreatic tissue.

PMID- 7567235
TI  - Familial type 1 jejunal atresias and renal dysplasia.
AB  - Three members of a family in two generations with proximal jejunal atresia and
      renal dysplasia are described. This association is presumably an autosomal
      dominant condition.

PMID- 7567236
TI  - Abnormal contralateral kidney in unilateral multicystic dysplastic kidney
      disease.
AB  - We performed a retrospective study of infants with unilateral multicystic
      dysplastic kidney (MCDK) in order to investigate the associated urological
      abnormalities. We examined the records of seven patients, in five of whom a
      diagnosis had been made prenatally using ultrasonography. Our investigation
      focused on the associated urological abnormalities, particularly on the
      contralateral side, and the results of voiding cystourethrography (VCUG). Four of
      the seven patients (57%) had urological abnormalities other than MCDK: three
      exhibited vesicoureteral reflux (VUR) of the contralateral side including one
      patient who also had an ipsilateral ectopic ureter, and the fourth patient had a
      ureterocele of the ipsilateral side. The results indicate that contralateral VUR,
      was the most common abnormality associated with MCDK. Two infants had high-grade
      VUR and underwent anti-reflux surgery soon after the diagnosis. Both have
      remained free of recurrent urinary tract infection.

PMID- 7567237
TI  - Unilateral abdominal wall hypoplasia: radiographic findings in two infant girls.
AB  - Prune belly syndrome (PBS) is defined as an association of abdominal wall
      deficiency, genitourinary anomalies, and, in males, cryptorchism. Although PBS is
      more common in males, females can also have the condition. In both sexes,
      expression of the disease is often incomplete and prognosis depends upon the
      specific abnormalities present. PBS in girls or incomplete expression of PBS is
      called pseudoprune belly syndrome (PPBS). We recently evaluated two baby girls
      with PPBS. Both girls had unilateral abdominal wall hypoplasia associated with
      cardiac, genitourinary, gastrointestinal, pulmonary, and musculoskeletal
      involvement that ranged from normal to severe. One of the patients also
      demonstrated congenital cytomegalovirus (CMV) infection and focal jejunal
      hypoganglionosis. Since CMV has been associated with both aganglionosis and PBS,
      it is possible that CMV induced both conditions in this patient.

PMID- 7567238
TI  - Elastofibroma dorsi: MRI diagnosis in a young girl.
AB  - Elastofibroma dorsi is a slowly growing tumour-like process composed of an ill
      defined mass of fibro-elastic tissue. It occurs almost exclusively in the elderly
      and is thought to result from mechanical friction. It has received little
      attention in the radiological literature and is considered a rare lesion. With
      indications for computerised imaging expanding, elastofibroma dorsi will probably
      be seen more frequently. This report describes an elastofibroma presenting in an
      11-year-old girl and its appearance by magnetic resonance imaging. Presumptive
      diagnosis by magnetic resonance imaging may prevent unnecessary radical surgery.

PMID- 7567239
TI  - Hemorrhagic intracranial parenchymal metastases from primary retroperitoneal
      neuroblastoma.
AB  - An unusual case of parenchymal hemorrhagic metastases to the cerebrum and
      cerebellum in a child with retroperitoneal neuroblastoma is presented. While
      isolated parenchymal central nervous system (CNS) metastases have not typically
      been considered in association with neuroblastoma, review of the literature
      suggests an increased frequency of this manifestation, especially since 1980.
      Metastatic neuroblastoma should be included in the differential diagnosis of
      multiple hemorrhagic parenchymal brain lesions in the pediatric population.

PMID- 7567240
TI  - Imaging features of ovarian metastases from colonic adenocarcinoma in
      adolescents.
AB  - This paper describes the imaging features of ovarian metastases from
      adenocarcinoma of the colon in adolescent females. We reviewed retrospectively
      abdominal and pelvic computed tomographic and pelvic ultrasound examinations,
      histologic slices, and clinical charts of six adolescent females with ovarian
      metastases secondary to adenocarcinoma of the colon. One patient had ovarian
      metastasis at presentation and was presumed to have a primary ovarian tumor. The
      ovarian metastases were either solid (n = 3), complex with both solid and cystic
      components (n = 2), or multilocular cysts (n = 1). The ovarian lesions were
      large, ranging from 6 cm to 18 cm in diameter. Colorectal carcinoma in adolescent
      females is frequently associated with ovarian metastases. One imaging
      characteristic differs in adult and adolescent ovarian metastases, although they
      do have features in common: in adolescents, a smaller proportion of colorectal
      ovarian metastases are multicystic (17%) compared with the adult series (45%).
      These lesions are frequently large and may be complex, multicystic, or solid.
      Although it is a rare disease, the differential diagnosis of adnexal masses in
      adolescent females should include ovarian metastases from adenocarcinoma of the
      colon.

PMID- 7567241
TI  - Shwachman-Diamond syndrome: clinical, radiological and sonographic aspects.
AB  - Six children with Shwachman-Diamond syndrome have been diagnosed and treated in
      our hospital since 1986. We describe the radiological and sonographic findings of
      this rare disease which is characterized by metaphyseal chondrodysplasia,
      neutropenia and pancreatic exocrine insufficiency. It presents with variable
      extremity shortening, "cup" deformation of the ribs, metaphyseal widening and
      hypoplasia of the iliac bones, and increased echogenicity of the pancreas without
      change in size. We discuss the differential diagnosis and review the literature.

PMID- 7567242
TI  - Oxalosis of bone: report of four cases and a new radiological staging.
AB  - Oxalosis of bone is caused by a combination of crystalline calcium oxalate
      deposition in bone and renal osteodystrophy in patients with chronic renal
      failure. The present paper presents the radiographic findings of oxalosis of bone
      in four patients who have been followed over a period of from 4 to 16 years. Four
      successive characteristic stages can be recognized in the development of the
      skeletal changes.

PMID- 7567243
TI  - Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple
      syrup urine disease.
AB  - Using localized proton magnetic resonance spectroscopy (1H-MRS), accumulation of
      branched-chain amino acids (BCAA) and their corresponding 2-oxo acids (BCOA)
      could be non-invasively demonstrated in the brain of a 9-year-old girl suffering
      from classical maple syrup urine disease. During acute metabolic decompensation,
      the compounds caused a signal at a chemical shift of 0.9 ppm which was assigned
      by in vitro experiments. The brain tissue concentration of the sum of BCAA and
      BCOA could be estimated as 0.9 mmol/l. Localized 1H-MRS of the brain appears to
      be suitable for examining patients suffering from maple syrup urine disease in
      different metabolic states.

PMID- 7567244
TI  - A new form of rhizo-mesomelic bone dysplasia.
AB  - A new form of rhizo-mesomelic dwarfism in an 8 1/2-year-old gypsy Slovakian girl
      is reported. This patient shows some superficial similarity to patients with
      Robinow syndrome. However, different facies, normal external genitalia and
      absence of radiographic abnormalities characteristic of Robinow syndrome
      (malsegmentation of the spine and ribs, short, small tubular bones and bifid
      terminal phalanges) as well as mesomelic hypoplastic/dysplastic changes in the
      forearm bones allow us to separate this disorder as a distinctive entity.

PMID- 7567245
TI  - Spondylo-epimetaphyseal dysplasia with joint laxity and severe kyphoscoliosis in
      an Italian girl.
AB  - A case of spondylo-epimetaphyseal dysplasia with joint laxity (SEMDJL) in an
      Italian girl is reported. This condition is mainly observed in the Afrikaans
      population of South Africa with an ancestral founder believed to be localized in
      West Germany. This case might support a link with the European origin of SEMDJL.

PMID- 7567246
TI  - Acute sinusitis in children: is the Water's view sufficient?
AB  - The purpose of this study was to examine the utility of the Water's view in the
      diagnosis of acute sinusitis in children. The records of all pediatric (less than
      18 years old) patients who underwent sinus radiography for suspected acute
      sinusitis between February 1991 and November 1992 were reviewed. All radiographs
      were reviewed by an attending radiologist and the interpretation of the Water's
      (occipitomental) view alone was compared to that of a three-view
      (anterior/posterior, lateral, Water's) series. Fifty-two three-view sinus series
      were obtained on pediatric patients during the study period. Twenty-eight
      patients were diagnosed with acute sinusitis based on the three-view series. When
      compared to the three-view series, the single Water's view had a sensitivity of
      89%, specificity of 83%, positive predictive value of 87%, and negative
      predictive value of 87%. The overall accuracy of the Water's view in diagnosing
      childhood acute sinusitis was 87%. The authors conclude that the Water's view is
      usually sufficient in the evaluation of suspected acute sinusitis in children.

PMID- 7567247
TI  - Esophageal involvement in chronic granulomatous disease. Case report and review.
AB  - A 5-year-old girl with chronic granulomatous disease (CGD) and esophageal
      narrowing is described. To date, only two cases of esophageal involvement in CGD
      have been reported. We present a third, well-documented case and a brief review
      of the literature.

PMID- 7567248
TI  - Evolving asymmetric hypertrophic pyloric stenosis associated with histologic
      evidence of eosinophilic gastroenteritis.
AB  - The most frequently occurring and important cause of gastric outlet obstruction
      in the neonate and young infant is infantile hypertrophic pyloric stenosis
      (IHPS). A reported association of IHPS and eosinophilic gastroenteritis [1]
      raises interesting questions about the possible etiologic relationship between
      the two entities. It is plausible that the observed sonographic pyloric muscular
      wall thickness in IHPS may in part be dependent on the degree and duration of an
      allergic gastroenteropathy. A recent report suggests that endoscopy may be a more
      reliable diagnostic method than sonography in the patient with evolving IHPS [2].
      Our recent experience with a patient with evolving IHPS supports the findings
      described in these prior reports.

PMID- 7567249
TI  - Spontaneous colonic ischemia in a patient with Riley-Day syndrome.
AB  - Familial dysautonomia, or Riley-Day syndrome, is a hereditary disturbance in the
      autonomic and peripheral sensory nervous systems, first described by Riley, Day,
      and colleagues in 1949 [1, 2]. Previous reports of myocardial infarction and
      avascular necrosis in bone suggest that these patients are at risk for ischemia
      at certain organ sites [3, 4]. We report a case of spontaneous colonic ischemia
      and stricture which resulted in colocutaneous fistula formation and eventual
      colonic resection in a child with Riley-Day syndrome.

PMID- 7567250
TI  - Aortic calcification and renal cysts demonstrated by CT in a teenager with
      Alagille syndrome.
AB  - Alagille syndrome, or arteriohepatic dysplasia, is a disorder characterized by
      paucity of intrahepatic bile ducts, peculiar facies and skeletal anomalies. We
      report a typical case of this syndrome in an 18-year-old girl, in whom abdominal
      CT showed bilateral renal cysts and aortic wall calcification, findings
      unreported in the radiological literature.

PMID- 7567251
TI  - MRI of congenital Foix-Chavany-Marie syndrome.
AB  - MRI findings of bilateral central macrogyria allowed the diagnosis of a
      congenital variant of Foix-Chavany-Marie syndrome in four patients aged between
      13 and 32 years, with facio-pharyngo-glosso-masticatory central diplegia, mental
      retardation and seizures.

PMID- 7567252
TI  - Intussusception reduction techniques.

PMID- 7567253
TI  - Blunt hepatic and splenic trauma in children: correlation of a CT injury severity
      scale with clinical outcome.
AB  - The purpose of this report is to compare a computed tomography (CT) injury
      severity scale for hepatic and splenic injury with the following outcome
      measures: requirement for surgical hemostasis, requirement for blood transfusion
      and late complications. Sixty-nine children with isolated hepatic injury and 53
      with isolated splenic injury were prospectively classified at CT according to
      extent of parenchymal involvement. Clinical records were reviewed to determine
      clinical outcome. Ninety-seven children (80%) were managed non-operatively
      without transfusion. One child with hepatic injury required surgical hemostasis,
      and 17 (25%) required transfusion of blood. Increasing severity of hepatic injury
      at CT was associated with progressively greater frequency of transfusion (P =
      0.002 by chi 2-test). One child with splenic injury underwent surgery and eight
      (15%) required transfusion of blood. Splenic injury grade at CT did not correlate
      with frequency (P = 0.41 by chi 2-test) or amount (P = 0.35 by factorial analysis
      of variance) of transfusion. There was one late complication in the nonsurgical
      group. A majority of children with hepatic and splenic injury were managed non
      operatively without requiring blood transfusion. The severity of injury by CT
      scan did not correlate with need for surgery. Increasing grade of hepatic injury
      at CT was associated with increasing frequency of blood transfusion. CT staging
      was not discriminatory in predicting transfusion requirement in splenic injury.

PMID- 7567255
TI  - Commentary: pediatric blunt abdominal trauma--to sound or not to sound?

PMID- 7567254
TI  - Commentary: sonography in the evaluation of children following blunt trauma: is
      it to be or not to be?
AB  - Over the past decade CT scanning has become generally accepted in North America
      as the diagnostic modality of choice for the evaluation of abdominal injury in
      children following blunt trauma [1-5]. Recently, there has been increasing
      interest in the use of sonography as the primary screening examination in this
      area. Initial studies utilizing sonography in the evaluation of trauma patients
      focused primarily on identifying hemoperitoneum in adults [6-8]. More recent
      studies have also attempted to evaluate the accuracy of sonography for the
      diagnosis of solid viscus injury [9-14]. Filiatraut and colleagues recently
      reported a long and successful experience using sonography for the investigation
      of blunt abdominal trauma in children [12]. Their work in this area should be
      applauded. However, whether widespread application of this modality can be
      successful remains uncertain. In the space below a critical evaluation of
      sonography and CT in the assessment of injured children is presented.

PMID- 7567257
TI  - Bypass cannulas utilized in extracorporeal membrane oxygenation in neonates:
      radiographic findings.
AB  - ECMO, as applied to neonates with severe respiratory failure, involves either a
      single or dual cannula system for removal of desaturated blood from and return of
      oxygenated blood to the patient. ECMO cannulas have undergone considerable change
      and improvement since the early 1980s, and a variety of cannulas are now
      available commercially for neonatal ECMO. All ECMO cannulas have a characteristic
      appearance on the chest radiograph, which is important in the assessment of
      cannula position and some cannula complications. We report the physical
      characteristics, advantages, disadvantages, and radiographic appearance of the
      most widely utilized neonatal ECMO cannulas.

PMID- 7567256
TI  - Tracheobronchomegaly in preterm infants on mechanical ventilation.
AB  - Tracheobronchomegaly (TBM) was diagnosed on chest radiographs as an apparent
      dilatation of the trachea and main bronchi in four premature infants on prolonged
      mechanical ventilation for respiratory distress syndrome. In a retrospective
      study, the parameters of assisted ventilation, the Apgar score, the presence of
      conatal or later infection, and hypotension were reviewed and analyzed as factors
      possibly contributing to the pathogenesis of TBM in these infants. The results
      lead to the conclusion that TBM in premature infants on prolonged ventilatory
      support is an acquired condition though a congenital defect cannot be excluded as
      a probable predisposing factor. In the etiopathogenesis of TBM, a repeated
      barotrauma of prolonged ventilation is a crucial factor while the severity of
      lung disease and the degree of prematurity, hypotension, infection, and generally
      poor clinical condition, all appear to be relevant in the development of TBM in a
      premature infant with respiratory distress syndrome.

PMID- 7567259
TI  - Reduced need for sedation in patients undergoing helical CT of the chest and
      abdomen.
AB  - Since 15 July 1993, we have used helical CT exclusively in chest and abdomen
      exams. The purpose of this study was to compare sedation rates in children
      undergoing conventional and helical CT of the chest and abdomen. Data for all CT
      examinations of the head (n = 1121), chest (n = 427), and abdomen (n = 315)
      performed between 1 April 1993 and 31 October 1993 were evaluated. Examinations
      were divided by anatomic site, patient age, date, whether motion was noted in the
      radiology report, and whether or not sedation was used. The oldest patient
      requiring sedation was 5 years old. All examinations in patients 5 years old or
      less (n = 1048) formed the study group. Because no head CT examinations were done
      helically, this constituted a control group. Comparisons of motion and sedation
      rates before and after 15 July 1993 were made with the chi 2 test. There was no
      statistically significant difference in the sedation rate in the control group
      (patients having conventional head CT examinations). In contrast, the use of
      helical technique for chest and abdomen CT coincided with a reduction of the
      sedation rate from 18% to 10% (P = 0.3). There was no statistically significant
      difference in reported motion for either head or chest/abdomen examinations over
      the study period. The implementation of helical CT coincided with a 45% reduction
      in the sedation rate of patients undergoing CT of the chest and abdomen. At the
      current volume of CT examinations at our institution, this decrease would result
      in an estimated 60 fewer sedations per year.

PMID- 7567258
TI  - Sedation in pediatric imaging using intranasal midazolam.
AB  - Intranasal midazolam offers an attractive alternative for use as a sedative agent
      for medical imaging studies in children. Its convenient administration and rapid
      onset are significant advantages over intravenous and oral agents. Because of its
      short duration, it is effective only for short procedures and as an adjunct to
      other sedative agents. When younger children present with such requirements, a
      dose of 0.2 mg/kg has been safe and effective in our experience. We advocate its
      use with adherence to guidelines for sedation published by the American Academy
      of Pediatrics.

PMID- 7567260
TI  - Comparison of helical and conventional chest CT in the uncooperative pediatric
      patient.
AB  - The objective of this study was to compare the quality of conventional and
      helical computed tomography (CT) images in children unable to breath-hold.
      Sixteen patients (age range 1.1-7.5 years) underwent both conventional and
      helical chest CT on a General Electric HiSpeed Advantage scanner at a mean study
      interval of 3.8 months. Conventional 0.6-s scans were reconstructed with standard
      algorithm while 1.0-s helical studies were reconstructed with standard and bone
      algorithms. Three blinded observers retrospectively evaluated the images. There
      was no significant difference in motion, image sharpness and anatomic resolution
      for helical and conventional scans reconstructed with standard algorithm.
      Furthermore, image sharpness (P < 0.001) and visibility of bronchi (P < 0.001)
      were improved when helical images were reconstructed with bone algorithm. We
      conclude that motion artifact severity, image sharpness and anatomic resolution
      for helical and conventional 0.6-s chest CT are similar when the images are
      reconstructed with an identical algorithm. Helical CT may be preferable because
      of the faster examination times and the ability to reconstruct overlapping images
      as an adjunct for problem solving. Also, with the scanner used, bone algorithm
      reconstruction can be employed to improve image sharpness and anatomic
      resolution.

PMID- 7567262
TI  - Radiological assessment of the hand and wrist in phenylketonuria and
      hyperphenylalaninaemia.
AB  - A radiograph of the left hand and wrist was taken in 141 children and young
      adults with phenylketonuria and hyperphenylalaninaemia. Ten (7.1%) had a bony
      abnormality and, of these, six (4.3%) showed evidence of reduced bone density.
      Only one patient had evidence of spiculation of the lower ulnar metaphysis
      previously described in phenylketonuria. Bone maturity was also assessed in 130
      patients by the Tanner-Whitehouse (TW2) method. In 28 patients (21.5%) bone age
      was less than chronological age by 1 year or more. Bone age delay was greater in
      younger children on a more restricted diet with a lower intake of natural
      protein.

PMID- 7567261
TI  - Late and acute adverse reactions to iohexol in a pediatric population.
AB  - The purpose of this study was to determine the incidence of acute and late
      reactions after contrast-medium injection in the Finnish paediatric population.
      From March 1989 to November 1990, 321 children under 19 years of age were
      examined with a nonionic contrast medium, iohexol, for urography and CT. The
      follow-up time for late reactions was up to 24 h after the contrast-medium
      injection. The return rate for the questionnaires given to patients to record
      their reactions was 73.2%. Acute adverse reaction was noted in 1.9% of the
      patients, with the most frequent reactions being in the weight range 24-40 kg.
      Asthma and previous reaction to contrast medium are risk factors for acute
      reaction. Late reactions were found in 6.2% of the patients, most frequently in
      children weighing under 24 kg.

PMID- 7567264
TI  - Foetal and neonatal splenic cyst-like lesions. US follow-up of seven cases.
AB  - Seven cases of small, asymptomatic splenic cyst-like lesions (CLL) diagnosed in
      foetuses and neonates are reported. None of these CLL was operated on; three
      completely disappeared. Such a complete regression has never been described
      before. A more conservative app approach to such lesions is suggested in order to
      prevent the possible complications of inappropriate interventional therapy.

PMID- 7567263
TI  - Shwachman-Diamond syndrome: clinical, radiological and sonographic findings.
AB  - Six children with Shwachman-Diamond syndrome have been diagnosed and treated in
      our hospital since 1986. We describe the radiological and sonographic findings of
      this rare disease, which is characterized by metaphyseal chondrodysplasia,
      neutropenia and exocrine pancreatic insufficiency. It presents with varying
      extremity shortening, "cup" deformation of the ribs, metaphyseal widening and
      hypoplasia of the iliac bones, as well as increased echogenicity of the
      normalized pancreas. We discuss the differential diagnosis and review the
      literature.

PMID- 7567266
TI  - Submandibular gland mucocele of the extravasation type. Report of two cases.
AB  - The clinical and radiological differential diagnosis of cystic lesions of the
      head and neck region can be difficult. We report two cases of submandibular gland
      mucoceles presenting as cystic masses in the submandibular region. The imaging
      characteristics and differential diagnosis are discussed.

PMID- 7567265
TI  - Cervical thymic cysts: CT appearance of two cases including a persistent
      thymopharyngeal duct cyst.
AB  - The differential diagnosis of cervical cysts in children includes common entities
      such as branchial cleft cysts, thyroglossal duct cysts, and cystic hygromas.
      Congenital thymic cysts are uncommon and often misdiagnosed as either branchial
      cleft cysts or cystic hygromas. However, they may have an appearance on CT that
      can be characteristic. The course of the descent of embryologic thymic tissue in
      the neck to the mediastinum indicates the potential site of deposition of an
      ectopic cervical thymic cyst. In a child, a cystic lesion that has an intimate
      relationship to the carotid sheath is likely to be a thymic cyst. Of the
      approximately 100 cases of vestigial cervical thymus or thymic cysts that have
      been reported in children, only 5 cases of a persistent thymopharyngeal duct cyst
      have been described [1-5]. In two of these five, the persistent thymopharyngeal
      duct cyst was demonstrated by CT [1,2]. We report one additional case of a
      cervical thymic cyst and one case of a persistent thymopharyngeal duct cyst both
      depicted by CT.

PMID- 7567268
TI  - Sonographic diagnosis and follow-up of diffuse neutropenic colitis: case report
      of a child treated for osteogenic sarcoma.
AB  - The sonographic features of total neutropenic colitis in a 14-year-old girl with
      osteogenic sarcoma are presented. Sonography disclosed characteristic diffuse
      thickening of the colonic wall with hyperechoic bowel mucosa. Serial sonograms
      were performed to monitor the progress of the disease.

PMID- 7567269
TI  - Scrotal swelling: unusual first presentation of Crohn's disease.
AB  - Crohn's disease often is detected in adolescents with nonspecific
      gastrointestinal complaints. Extraintestinal complications are common but usually
      follow the onset of the bowel complaints. We present an unusual case in which
      scrotal swelling was the first symptom in a patient discovered to have Crohn's
      disease.

PMID- 7567270
TI  - Lower genitourinary tract anomalies in a male with Down syndrome.
AB  - A patient with Down syndrome is presented who had hypospadias, a large low
      implanted prostatic utricle, and refluxing ejaculatory ducts entering the
      utricle.

PMID- 7567272
TI  - Ectopia of the vas deferens.
AB  - We present a case of bilateral ectopic vas deferens with insertion in the
      posterior bladder, a rare congenital anomaly related to abnormal distal Wolffian
      duct development. Common presentations include urinary tract infections,
      epididymitis or a swollen scrotum although this abnormality can be an
      asymptomatic, incidental finding. There is also a strong association with
      anorectal malformations, ureteral ectopia and vesicoureteral reflux.

PMID- 7567267
TI  - Plasma cell granuloma of the lung in childhood: atypical radiologic findings and
      association with hypertrophic osteoarthropathy.
AB  - Three cases of pulmonary plasma cell granuloma in the pediatric age group are
      presented. Although rare, it is the most frequent primary lung tumor in
      childhood. In two of the cases, there was a close adherence between the tumor and
      the surrounding mediastinal structures and diaphragm, a very uncommon feature in
      these tumors. In the other case, plasma cell granuloma of the lung was seen in
      association with a clinical-radiological picture of hypertrophic
      osteoarthropathy, which resolved after excision of the mass. Such an association
      has not, to date, been reported in the literature, and could constitute an
      additional finding useful in the differential diagnosis of primary lung tumors in
      childhood. The literature concerning this issue has been reviewed.

PMID- 7567273
TI  - Gastric teratoma with intramural extension.
AB  - Gastric teratoma is an extremely rare neoplasm which accounts for less than two
      percent of all teratomas. Unlike other teratomas, gastric teratomas are all
      benign and predominantly occur in males. As gastric teratomas generally present
      as a palpable abdominal mass, more aggressive solid masses of childhood must be
      excluded. In this case, CT imaging delineates both cystic and fatty components
      characteristic of teratoma and displays the rare gastric origin of the lesion.

PMID- 7567275
TI  - Hemimegalencephaly associated with contralateral hemispheral volume loss.
AB  - Hemimegalencephaly is a rare malformation characterized by overdevelopment of one
      cerebral hemisphere. The opposite hemisphere is usually normal. This paper
      presents a 2-day-old patient with hemimegalencephaly associated with diffuse
      volume loss in the contralateral hemisphere. To the best of the author's
      knowledge such an association has not been reported previously. This finding
      suggested that these patients may suffer from a congenital hemispheral insult of
      varying degree of severity and variable time of onset.

PMID- 7567274
TI  - Anterior callosal agenesis in mild, lobar holoprosencephaly.
AB  - The corpus callosum normally grows in a ventral to dorsal direction with the genu
      appearing first followed by posterior growth to form the body and splenium. In
      holoprosencephaly there usually is a malformation of the lamina terminalis which
      results in lack of formation of the corpus callosum. This paper presents a
      patient with mild, lobar holoprosencephaly in whom a different type of callosal
      dysgenesis was detected: the callosal body and splenium were apparently formed
      but the anterior parts were absent. The existence of this type of callosal
      dysgenesis appears to be in contrast to current theories on callosal development.

PMID- 7567271
TI  - Cystic dysplasia of the testis associated with multicystic dysplastic kidney.
AB  - Cystic dysplasia of the testis (CDT) is a rare congenital defect characterized by
      the formation of multiple irregular cystic spaces in the mediastinum testis. Co
      existent genitourinary lesions have commonly been associated with this lesion and
      have included absence of the ipsilateral kidney, duplication anomalies, and
      cryptorchidism. We describe the first case in which multicystic dysplastic kidney
      (MCDK) is associated with CDT.

PMID- 7567276
TI  - Spectrum of chest radiographic abnormalities in children with AIDS and
      Pneumocystis carinii pneumonia.
AB  - This report aims to provide a description of the spectrum of radiographic
      findings in children with AIDS and Pneumocystis carinii pneumonia (PCP). The
      chest radiographs of all children with perinatally transmitted HIV infection who
      had PCP were reviewed. Thirty-eight episodes of PCP were noted in 32 children.
      The age range was 2-17 months. The radiographic findings were characterized as to
      pattern, severity, presence of pulmonary air cyst, thoracic air leak, thoracic
      lymphadenopathy, and pleural effusion. The initial distribution of disease was as
      follows: diffuse (n = 20), patchy (n = 12), focal (n = 4), normal (n = 2). In
      nearly one-third of children parenchymal abnormalities were mild enough that most
      normal lung markings were visible. During the course of the illness pneumothorax
      was noted in eight cases, pulmonary air cyst in five, and pneumomediastinum in
      one. Pleural effusions were noted in three (5%) cases. Thoracic lymphadenopathy
      was not observed in any case. The authors concluded that the initial chest
      radiographic appearance of PCP in children with AIDS is variable. The initial
      chest radiograph may be normal. The distribution was patchy or focal in nearly
      one-half of all cases with parenchymal abnormalities. Pulmonary air cysts or
      thoracic air leaks were noted during the course of the illness in approximately
      one-third of all cases.

PMID- 7567278
TI  - Sonographic and radiographic appearance of lesions in an infant with Langerhans'
      cell histiocytosis.

PMID- 7567277
TI  - Application of thin-section low-dose chest CT (TSCT) in the management of
      pediatric AIDS.
AB  - The aim of this study was to evaluate the usefulness of thin-section low-dose
      computed tomography (TSCT) in the management of children with AIDS, as chest
      radiographs (CXR) often fail to adequately explain the patients' clinical status.
      We performed 54 noncontrast TSCTs on 32 children. The patients aged from 3 months
      to 14.6 years, were diagnosed as having bacterial pneumonia, lumphocytic
      interstitial pneumonitis (LIP), Pneumocystis carinii pneumonia (PCP), or
      Mycobacterium avium-intracellulare infection (MAI). The scans were correlated
      with the clinical diagnosis, T-lymphocyte-subset percentages, and p24-antigen
      levels. Subsegmental consolidations were seen in patients with LIP, PCP, and MAI,
      and as an isolated finding in those with only bacterial pneumonia. Ground-glass
      haziness was seen exclusively with acute PCP. Reticulonodular thickening was
      identified only in patients with LIP. Mosaic perfusion was seen with MAI, LIP,
      and pneumonia. The presence of adenopathy correlated with CD4+ T-cell subset
      percentages. The greatest value of CT in this study was in detecting new disease
      when chest films failed to correlate with a patient's clinical state, and in
      demonstrating acute/subacute disease in patients with severe baseline chest-film
      changes. Recurrent pneumonias may represent progression of "smoldering" disease,
      rather than true recurrent disease following complete clearing. Adenopathy with
      low CD4+ levels should suggest lymphoma or infection with MAI.

PMID- 7567279
TI  - Ultrasonographic features of recurrent parotitis in childhood.

PMID- 7567280
TI  - A curriculum in pediatric radiology for diagnostic radiology residents. Education
      and Training Committee, Society for Pediatric Radiology.

PMID- 7567281
TI  - Application of new sepsis definitions to evaluate outcome of pediatric patients
      with severe systemic infections.
AB  - No published reports have stratified pediatric patients with systemic infections
      according to the new sepsis terminology guidelines. In addition little is known
      about the outcome of sepsis in developing countries. This large 12-year
      retrospective study evaluated the outcome of 815 infants and children with sepsis
      managed in a Latin American pediatric intensive care unit. Of these children 171
      (21%) had sepsis, 497 (61%) had severe sepsis and 147 (18%) had septic shock.
      Multiorgan dysfunction was present in 120 (24%) and 77 (52%) patients with severe
      sepsis and septic shock, respectively. Infection was bacteriologically proved in
      212 (26%) cases, with Staphylococcus aureus and Neisseria meningitidis being the
      most frequent responsible organisms. Three hundred nineteen (39%) patients died.
      Case-fatality rates were higher in patients with septic shock, multiorgan
      dysfunction, sepsis caused by Pseudomonas aeruginosa and meningococcemia than in
      those without these conditions. Although no difference in mortality was detected
      between culture-proved and culture-negative sepsis, more patients receiving an
      inappropriate antimicrobial agent died than those treated with an appropriate
      drug (53% vs. 34%, P = 0.012). We believe that with the use of the new
      terminology system a more reliable comparison of data from pediatric sepsis
      studies and of emerging immunomodulating therapeutic modalities can be achieved.

PMID- 7567282
TI  - Estimating immunization coverage from school-based childhood immunization
      records.
AB  - To determine the accuracy of school-based childhood immunization records and to
      describe the effects of their use on estimates of community-wide immunization
      coverage, we verified the immunizations to 72 months of age for children born in
      1986 to residents in Dallas County, TX, and in Minnesota. Verified immunizations
      were compared with those documented in the school record. Major transcription
      errors accounted for fewer than 1% of discrepancies between school and provider
      records. For 99 subjects with 987 verified immunizations in Minnesota, age
      appropriate immunization coverage estimated from the school records was within
      two percent of actual coverage. For 86 subjects with 981 verified immunizations
      in Dallas County, age-appropriate immunization coverage from the school records
      underestimated actual coverage by as much as 21%. The primary factor explaining
      the underestimate in Dallas was incomplete school immunization records for 33
      (38%) subjects and 126 (13%) immunizations. Selective recording of immunizations
      related to the minimum state requirements in Texas contributed to incomplete
      school records in Dallas County. Verification of the completeness of records
      selected to estimate immunization coverage is essential if the estimates are used
      to monitor trends or to make public policy decisions.

PMID- 7567283
TI  - Local massage after vaccination enhances the immunogenicity of diphtheria-tetanus
      pertussis vaccine.
AB  - The effect of local massage on adverse reactions and immunogenicity of diphtheria
      tetanus-pertussis vaccine was investigated. After diphtheria-tetanus-pertussis
      vaccination 327 infants were either massaged or not, and adverse reactions were
      evaluated. Local pain and fever were more frequent in the massage group. The
      extra febrile episodes from massage were mild (38-39 degrees C). For evaluation
      of the antibody responses, 124 infants were recruited into massage or nonmassage
      cohorts and antibody production was measured at 2, 6, 7, 18 and 19 months of age,
      respectively. Subjects in the massage group developed significantly higher
      antibodies against filamentous hemagglutinin at 6 and 7 months of age, pertussis
      toxin at 6, 7, 18 and 19 months of age, pertussis agglutinogen at 18 and 19
      months of age and those in the nonmassage group. Local massage after diphtheria
      tetanus-pertussis vaccination was associated with better immunogenicity and more
      adverse reactions, including low grade fever and local pain, which were mild and
      not particularly disturbing.

PMID- 7567284
TI  - High incidence of congenital rubella syndrome after a rubella outbreak.
AB  - Previous studies of the incidence of congenital rubella syndrome (CRS) after
      rubella outbreaks have been limited because most women with infection during the
      first trimester elected to have their pregnancies terminated. After a rubella
      outbreak in 1991 we measured prospectively the impact of maternal infection on
      CRS among the Amish in one county in Pennsylvania. We compared rubella serology
      of Amish women delivering before and after the outbreak and cord blood rubella
      IgM from Amish and non-Amish infants. Before the outbreak 20% of Amish women were
      susceptible to rubella; after the outbreak 4% were (P = 0.001). Of Amish infants
      15% tested positive for rubella IgM; no non-Amish infants did (P < 0.001). This
      rubella outbreak in a largely unimmunized community led to a high rate of CRS.
      The annual CRS rate among the Amish was 2130/100,000 live births. Health care
      providers should promote immunization in all clients and intensify efforts among
      the Amish.

PMID- 7567285
TI  - Prospective study of Yersinia enterocolitica infection in thalassemic patients.
AB  - We determined prospectively during a 12-month period the incidence, clinical
      characteristics and outcome of Yersinia enterocolitica infection in 144
      thalassemic patients (mean age, 12.8 years) and compared them with 100 controls
      (mean age, 12.1 years). Symptomatic Y. enterocolitica infection occurred in 14
      (10%) of the thalassemic patients and in 2 (2%) controls (P = 0.017). Of the 14
      thalassemic patients 5 (36%) had septicemia and 9 (64%) had focal infection
      (enteritis in 8 and tonsillitis in 1). One control patient had acute enteritis
      and the other had tonsillitis. All isolates from these patients belonged to
      pathogenic phenotypes of Y. enterocolitica. Pending culture results symptomatic
      thalassemic patients discontinued treatment with deferoxamine and were treated
      with intravenous antibiotic therapy. Patients with the ultimate diagnosis of
      focal Y. enterocolitica infection continued treatment with intramuscular
      ceftriaxone or intravenous trimethoprim/sulfamethoxazole (TMP/SMX) for 7 days,
      whereas those with septicemia continued treatment with intravenous TMP/SMX for 14
      days. The outcome was favorable in all 14 thalassemic patients. We conclude that
      Y. enterocolitica is a significant cause of morbidity in our patients with
      thalassemia and that prompt antibiotic therapy might prevent life-threatening
      conditions as well as a complicated course with long term sequelae.

PMID- 7567287
TI  - Group A streptococcal necrotizing fasciitis complicating primary varicella: a
      series of fourteen patients.
AB  - We retrospectively reviewed the clinical course of group A Streptococcus
      necrotizing fasciitis complicating primary varicella in children admitted to
      Children's Hospital and Medical Center, Seattle, WA, during a 18-month period.
      The potential benefit of various therapeutic interventions was examined. Fourteen
      children ages 6 months to 10 years were treated for group A Streptococcus
      necrotizing fasciitis as a complication of primary varicella. Eight patients
      experienced a delay in initial diagnosis as a result of nonspecific, early
      clinical findings of necrotizing fasciitis. Each patient underwent surgical
      exploration with fasciotomies and debridement. Initial antibiotic therapy was
      broad spectrum and included clindamycin. Hyperbaric oxygen therapy for as many as
      6 treatments was used as adjunctively therapy in 12 patients, with subjective
      benefit in 6 patients. All 14 patients were discharged home with good function
      and no long term sequelae. This potentially fatal bacterial infection of the deep
      fascial layers requires early recognition by primary care physicians and an
      intensive, multidisciplinary therapeutic approach, including thorough surgical
      debridement and appropriate antibiotic therapy.

PMID- 7567286
TI  - Molecular identification of viruses in sudden infant death associated with
      myocarditis and pericarditis.
AB  - A subset of infants dying suddenly and unexpectedly have myocarditis with or
      without pericarditis found at autopsy. To address whether viruses known to cause
      infantile myocarditis and pericarditis might be present in such infants, we
      examined myocardium, liver and skeletal muscle for the presence of genomic
      sequences from adenovirus, cytomegalovirus, enterovirus and echovirus 22/23 in
      infants enrolled in a comprehensive evaluation protocol. We studied eight infants
      who died suddenly and unexpectedly with histologic evidence of myocarditis and/or
      pericarditis detected at postmortem examination. One infant with myocarditis and
      pericarditis had adenovirus genome detected in the myocardium. In an additional
      infant with severe pericarditis alone, enterovirus genome was detected in the
      liver. Although echovirus 22/23 has been associated with myopericarditis in young
      infants, no previous studies have used molecular methods to search for the
      genomic sequences of these viruses in clinical samples. No echovirus 22/23 genome
      was detected in the patients reported here. The significance of enterovirus and
      adenovirus genome in the tissues of two patients dying suddenly and unexpectedly
      remains speculative but raises the possibility that pathogenic viruses may cause
      little or no clinical symptoms and yet be contributory to sudden death in young
      infants.

PMID- 7567288
TI  - Tumor necrosis factor concentrations in hemolytic uremic syndrome patients and
      children with bloody diarrhea in Argentina.
AB  - Hemolytic uremic syndrome (HUS) is thought to be a vascular endothelial injury
      disease. The mechanism of injury is unknown although verocytotoxins (Shiga-like
      toxins (SLTs)) are known to be associated with it. Recent evidence suggests that
      in vitro treatment of some endothelial cells with tumor necrosis factor alpha
      (TNF-alpha) dramatically increases their susceptibility to SLTs. We studied 25
      children with HUS, 63 children with SLT-positive bloody diarrhea, 62 children
      with bloody diarrhea not associated with SLTs and 39 children admitted for
      elective surgery, included as an age- and season-matched control group. The TNF
      alpha concentrations were found to be significantly elevated in children with HUS
      (range, 1 to 95 pg/ml; geometric mean, 32.2 pg/ml) compared with the healthy
      controls (range, 0 to 53 pg/ml; mean, 12.5 pg/ml; P < 0.001). Because it is
      hypothesized that TNF-alpha elevation might precede development of HUS, we also
      studied children with blood diarrhea. The TNF-alpha serum concentrations were
      significantly higher during the first 10 days after onset of bloody diarrhea than
      after the first 10 days (P < 0.02). Such elevation could be associated with
      vascular endothelial glycolipid receptor up-regulation and increased
      susceptibility to the effects of SLTs.

PMID- 7567289
TI  - Role of Clostridium difficile in childhood diarrhea.
AB  - To investigate the etiologic role of Clostridium difficile in childhood acute
      diarrhea, stool specimens from 618 children with diarrhea and 135 controls
      without enteric symptoms were examined by cell culture assay for the presence of
      free toxin B. This toxin was found in 4.2% of the fecal specimens examined
      without finding a significant difference between cases and controls, suggesting
      no causal relationship between diarrhea and the presence of free C. difficile
      toxin B. C. difficile strains isolated from toxin B-positive specimens were
      characterized by cytotoxin and enterotoxin production and by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of EDTA-extracted proteins. All but
      two isolates produced toxin B and toxin A and the remaining were negative for
      both toxins. Polyacrylamide gel electrophoresis analysis showed eight
      electrophoretic types, none of them was clearly related with the cases of
      diarrhea. The majority of isolates from children with diarrhea did not belong to
      types previously observed in adults with pseudomembranous colitis or antibiotic
      associated diarrhea. This study provides additional evidence that C. difficile is
      not involved in the etiology of childhood diarrhea.

PMID- 7567292
TI  - Tuberculosis in a day-care center, Kentucky, 1993.
AB  - In November, 1993, a 33-month-old child in a day-care center was diagnosed with
      tuberculosis (TB). To identify her source of infection, close contacts, other day
      care children and staff were screened by tuberculin skin test (TST). TB registry
      and medical/laboratory records were reviewed. The only 2 community TB cases
      reported in the past 3 years were investigated. Of 164 children 2 were diagnosed
      with TB; their TSTs were > or = 10 mm but no specimens were obtained. Six
      children had TSTs > or = 5 mm. Of these 4 had TST conversions between December,
      1993, and March, 1994. There were no additional positive TST children in June,
      1994. No TB case was identified among staff or parents. A possible epidemiologic
      link with the index case was found for 1 community case. No source of infection
      was found for the other children. Possible explanations for not finding a source
      are: an as yet unidentified case in the day-care center or community; or false
      positive TST results in children related to low community prevalence of TB
      infection.

PMID- 7567291
TI  - Risk of diarrheal disease in Ecuadorian day-care centers.
AB  - To determine the risk for diarrheal disease (DD) in day-care centers (DCC) for
      children residing in a poor urban slum area of Quito, Ecuador, compared with that
      for children from the same environment but cared for in their own residential
      home (RH), a prospective age-, sex- and locale-controlled study of DD was
      conducted, including 115 children in DCC and 115 in RH, ages 12 to 42 months. The
      overall incidence of DD was 46/1000 child weeks. Diarrhea was more common in DCC
      than in RH (relative risk (RR), 1.75; 95% confidence interval (CI), 1.38 to 2.22;
      P < 0.001). Poor hygienic practices were more prevalent in DCC than in RH. The
      use of reused water for child handwashing before eating and for washing raw
      vegetables was associated with a higher risk of DD in DCC than in RH (RR = 4.08,
      CI 2.93 to 5.67, P < 0.001; RR = 3.90, CI 2.79 to 5.44, P < 0.001, respectively).
      These two practices were risk factors in the DCC (RR = 2.74, CI 2.08 to 3.68, P <
      0.001; RR = 2.05, CI 1.55 to 2.71, P < 0.001, respectively) when compared with
      their absence in the same DCC. Shigella (RR = 3.58, CI 1.19 to 10.78, P < 0.02),
      Aeromonas (RR = 10.47, CI 1.35 to 81.05, P < 0.01), rotavirus (RR = 2.86, CI 1.87
      to 4.39, P < 0.001) and Giardia (RR = 1.59, CI 1.00 to 2.59, P < 0.05) were more
      common in DCC than in RH. More than two-fifths of the Shigella and Aeromonas
      isolates were resistant to trimethoprim-sulfamethoxazole.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7567290
TI  - Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and
      aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in
      children.
AB  - An increase in the incidence of Salmonella typhi strains resistant to
      chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole causing enteric
      fever in Egyptian children stimulated the evaluation of alternative drugs.
      Children with positive blood cultures were treated with cefixime, ceftriaxone or
      aztreonam, and the efficacy, safety and cost of these regimens were evaluated and
      compared. Cefixime (7.5 mg/kg) was given orally twice daily to 50 children for 14
      days, ceftriaxone (50 to 70 mg/kg) was given im once daily for 5 days to 43
      children and aztreonam (50 to 70 mg/kg) was given im every 8 hours for 7 days to
      31 children. Children in the 3 groups were comparable with regard to age, sex,
      duration and severity of illness before admission. All children were cured. A
      significant difference (P < 0.05) in duration of treatment before becoming
      afebrile seemed to favor ceftriaxone (3.9 days) over aztreonam (5.5 days) and
      cefixime (5.3 days). During the 4-week follow-up period relapses occurred in 3
      (6%) children in the cefixime group, in 2 (5%) in the ceftriaxone group and in 2
      (6%) in the aztreonam group. Safety and efficacy were comparable for all 3 drugs.
      Ceftriaxone was most cost-effective on an inpatient basis, because of a more
      rapid clinical cure, and cefixime was the most cost-effective on an outpatient
      basis, because of drug cost.

PMID- 7567294
TI  - Long term follow-up of Estonian children after bacterial meningitis.

PMID- 7567293
TI  - Lateral sinus thrombosis associated with otitis media and mastoiditis in
      children.
AB  - Lateral sinus thrombosis (LST) is an infrequent complication of otitis media and
      mastoiditis in the antibiotic era. A recent case of LST in a 7-year-old boy, the
      third such case at our institutions in the past 5 years, prompted a review of the
      modern day English literature concerning LST in pediatric patients. Our goal was
      to highlight the clinical findings suggestive of LST in the antibiotic era as
      well as to analyze retrospectively the diagnostic and therapeutic modalities of
      greatest benefit based on the outcomes reported in the reviewed studies.

PMID- 7567295
TI  - Comparison of two modes of mass delousing in schoolchildren.

PMID- 7567297
TI  - Symptomatic hepatitis A virus infection during the first year of life.

PMID- 7567296
TI  - Otogenic Fusobacterium necrophorum meningitis in children.

PMID- 7567298
TI  - Cytomegalovirus sinus disease in a human immunodeficiency virus-infected child.

PMID- 7567299
TI  - Treatment of Mycobacterium marinum facial abscess using clarithromycin.

PMID- 7567300
TI  - Staphylococcal enterotoxin A involvement in the illness of a 20-month-old burn
      patient.

PMID- 7567301
TI  - Bacteremia in neutropenic children.

PMID- 7567303
TI  - Prevalence of persistent diarrhea in Mexico.

PMID- 7567302
TI  - Rickettsial spotted fever infections: another pediatric indication for
      fluoroquinolones?

PMID- 7567304
TI  - Human herpesvirus 6 mononucleosis and seizures.

PMID- 7567305
TI  - Alcaligenes xylosoxidans-associated infection in an infant with cholesteatoma.

PMID- 7567306
TI  - Enterobacter septicemia in neonates.

PMID- 7567308
TI  - Efficacy of the combined diphtheria-tetanus toxoids-pertussis-Haemophilus
      conjugate vaccine.

PMID- 7567307
TI  - "Cheap torches": an acronym for congenital and perinatal infections.

PMID- 7567309
TI  - Ceftibuten vs. penicillin V in group A beta-hemolytic streptococcal pharyngitis.
      Members of the Ceftibuten Pharyngitis International Study Group.
AB  - The efficacy and safety of a 10-day course of ceftibuten oral suspension (9 mg/kg
      once daily) were compared with those of penicillin V (25 mg/kg/day in 3 divided
      doses) in children 3 to 18 years old treated for symptomatic pharyngitis and
      scarlet fever caused by group A beta-hemolytic streptococci (Streptococcus
      pyogenes). The study was prospective, randomized, multicenter and investigator
      blinded; patients were randomized in a 2:1 ratio (ceftibuten:penicillin V).
      Overall clinical success (cure/improvement) at the primary end point of treatment
      (5 to 7 days posttherapy) was achieved in 97% (285 of 294) of ceftibuten-treated
      patients vs. 89% (117 of 132) of penicillin V-treated patients (P < 0.01).
      Elimination of infecting streptococci 5 to 7 days posttherapy was achieved in 91%
      (267 of 294) of ceftibuten-treated patients vs 80% (105 of 132) of penicillin V
      treated patients (P < 0.01). A significant rise in anti-streptolysin O or anti
      DNase B was observed in approximately 30% of patients in both treatment groups.
      No patient developed rheumatic fever or nephritis. Treatment-related adverse
      events were similar between the two groups; mild vomiting (2%) was most
      frequently reported. These data suggest that once daily ceftibuten is as safe as
      and more effective than three times daily penicillin V for the treatment of group
      A beta-hemolytic streptococcal pharyngitis.

PMID- 7567312
TI  - Rational selection of antimicrobials for pediatric upper respiratory infections.
AB  - Antibiotic selection is complicated by both emerging resistance to traditional
      antimicrobials in common community-acquired pathogens and increasing numbers of
      high potency or extended spectrum antimicrobials. This overview outlines a
      multistep process for antibiotic choice based on antimicrobial activity and
      patient acceptance. Understanding the infection (the natural history and most
      likely pathogens) is necessary for choosing a specific antimicrobial. Choices
      should be based on knowledge of local trends in and mechanisms of antimicrobial
      resistance. Candidate drugs should also exceed (at the site of infection) the
      minimum inhibitory concentration for 90% of strains of each most likely pathogen.
      Ideally the narrowest spectrum drug satisfying this pharmacodynamic requirement
      is used. However, inadequate compliance dooms even the most potent antibiotic.
      Therefore infrequent dosing, palatable taste or form, minimal side effects or
      lower cost may dictate choosing lower potency or narrower spectrum drugs to gain
      patient acceptance and thereby reasonable compliance.

PMID- 7567310
TI  - Multicenter controlled trial comparing ceftibuten with amoxicillin/clavulanate in
      the empiric treatment of acute otitis media. Members of the Ceftibuten Otitis
      Media United States Study Group.
AB  - The efficacy and safety of ceftibuten (9 mg/kg daily for 10 days) were compared
      with those of amoxicillin/clavulanate (Augmentin 40 mg/kg/day given every 8 hours
      for 10 days) in the empiric treatment of acute otitis media in children. This was
      a multicenter, investigator-blinded study with 1:1 randomization. Overall
      clinical response and signs and symptoms of otitis were collected prospectively
      pretreatment, 3 to 5 days during treatment, 1 to 3 days post-treatment and at 2-
      to 4-week follow-up. In addition to spontaneous reports of other adverse events,
      gastrointestinal adverse events were prospectively elicited at each visit. Two
      hundred ninety-six patients (146 ceftibuten and 150 amoxicillin/clavulanate) were
      treated with at least 1 dose of study medication. Compliance with dosing was
      assessable with weight of drug consumed in 127 patients in each treatment group.
      Five percent (6 of 127) of ceftibuten patients and 11% (14 of 127) of
      amoxicillin/clavulanate patients received < 80% of prescribed drug (P = 0.10) and
      were therefore not valid. Two hundred twenty-two patients (121 ceftibuten and 101
      amoxicillin/clavulanate) received a minimum of 80% of prescribed medication and
      were compliant with the protocol. Ceftibuten and amoxicillin/clavulanate groups
      were comparable both for demographic variables and for baseline signs and
      symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567311
TI  - Multinational multicenter controlled trial comparing ceftibuten with cefaclor for
      the treatment of acute otitis media. Members of the Ceftibuten Otitis Media
      International Study Group.
AB  - A randomized, controlled, single blind clinical trial was conducted in children
      with acute otitis media to evaluate the safety and efficacy of a 10-day course of
      therapy with ceftibuten 9 mg/kg taken as a single daily dose, up to a maximum
      daily dose of 400 mg, compared with cefaclor 40 mg/kg/day in three divided doses,
      up to a maximum of 1 g/day. Patients were evaluated any time from 1 to 3 days
      after completion of therapy (posttreatment follow-up). A total of 154 patients
      (106 ceftibuten, 48 cefaclor) were evaluable for efficacy. Clinical success as
      determined by resolution (cure) or improvement of signs and symptoms of infection
      were seen in 89 and 88% of patients treated with ceftibuten and cefaclor,
      respectively, at the posttreatment follow-up visit. At the extended follow-up
      visit (any time from 2 to 4 weeks after completion of therapy), clinical success
      was sustained in 88 and 82% of the ceftibuten-treated and cefaclor-treated
      patients, respectively. A total of 391 patients (264 ceftibuten, 127 cefaclor)
      were included in the safety analysis. Treatment-related adverse experiences
      occurred in 8% of ceftibuten-treated patients and 14% of cefaclor-treated
      patients. All were mild or moderate and the majority were gastrointestinal. There
      were no deaths or serious adverse events. The results of this study suggest that
      ceftibuten is an effective and well-tolerated alternative to other antibiotic
      therapies for the treatment of children with acute otitis media.

PMID- 7567313
TI  - Worldwide safety experience with ceftibuten pediatric suspension.
AB  - Ceftibuten suspension was administered to 1312 pediatric patients in clinical
      trials at a dosage of 9 mg/kg once daily, with a maximal daily dose of 400 mg.
      Adverse experiences were collected by voluntary reports by physicians from direct
      observations, parental and/or patient complaints in 1152 patients. In 160
      patients gastrointestinal adverse experiences were elicited at each visit in
      addition to voluntary reports. Patients had a mean age of 4.9 years, the male:
      female ratio was 1:1 and 72% were white. Fifty-five percent (719 of 1312) of
      patients were treated in otitis media studies, 33% (438 of 1312) were treated in
      a pharyngitis study and 12% (155 of 1312) were treated in other studies. Adverse
      experiences occurred in 10% (138 of 1312) of all patients receiving ceftibuten
      suspension. The most common voluntarily reported treatment-related adverse events
      were diarrhea 3% (34 of 1152) and vomiting 2% (22 of 1152). For elicited adverse
      events related to treatment, the most common were also diarrhea 9% (14 of 160)
      and vomiting 3% (5 of 160). There were no deaths and only 0.9% (12 of 1312)
      patients discontinued treatment because of adverse events. Abnormal laboratory
      values related to therapy were uncommon and no patient discontinued treatment
      because of abnormal laboratory values. No cases of Stevens-Johnson syndrome,
      toxic epidermal necrolysis, serum sickness-like reactions or pseudomembranous
      colitis have been observed with ceftibuten suspension in research studies to
      date.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567314
TI  - Ceftibuten: a review of antimicrobial activity, spectrum and other microbiologic
      features.
AB  - Ceftibuten is a new, orally administered cephalosporin with exceptional beta
      lactamase stability and potency against commonly isolated Gram-negative
      pathogens. More than 90% of recent Enterobacteriaceae clinical isolates were
      inhibited by < or = 8 micrograms/ml of ceftibuten. In only five enteric species
      (Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella
      morganii, Serratia marcescens) were more than 15% of strains resistant (minimal
      inhibitory concentrations (MIC, with percent of strains inhibited in subscript
      numbers) > 16 micrograms/ml) to ceftibuten. Enteritis-producing bacteria such as
      Salmonella, Shigella, Escherichia coli and Yersinia were very ceftibuten
      susceptible (MIC50 < or = 0.13 microgram/ml). Fastidious Gram-negative species
      causing respiratory tract or genital infections had very low ceftibuten MICs,
      including beta-lactamase-positive Haemophilus influenzae (MIC90 0.06 to 2
      micrograms/ml), Moraxella catarrhalis (MIC90 0.25 to 4 micrograms/ml), and
      Neisseria gonorrhoeae (MIC90 0.015 to 0.5 microgram/ml). Beta-hemolytic
      streptococci and penicillin-susceptible pneumococci were also inhibited by
      ceftibuten. Staphylococci, enterococci, Pseudomonas species and Gram-negative
      anaerobic bacteria were generally resistant to ceftibuten. Ceftibuten has
      demonstrated bactericidal activity against susceptible pathogens, has high
      affinity for several lethal penicillin-binding proteins and possesses stability
      to common plasmid- or chromosomal-mediated beta-lactamases, including those
      enzymes that hydrolyze parenteral third generation cephalosporins. The
      microbiologic features for ceftibuten indicate its clinical potential as
      chemotherapy for community-acquired respiratory tract infections.

PMID- 7567315
TI  - Postantibiotic effect of ceftibuten on respiratory pathogens.
AB  - The postantibiotic effect (PAE) of ceftibuten, a novel beta-lactamase-stable
      cephem, was determined for Streptococcus pyogenes, Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella catarrhalis. The ceftibuten PAE after a 2
      hour exposure to 2 micrograms/ml (4 x minimum inhibitory concentration) for S.
      pyogenes was 2.7 to > 10 hours. The PAE for S. pneumoniae after a 2-hour exposure
      to 15 micrograms/ml, concentrations that are achieved in man after usual
      therapeutic doses, was 1.1 to 3.4 hours and the PAE for H. influenzae was 1 to
      1.1 hours. M. catarrhalis had a PAE of 1.5 to 1.8 hours after exposure to 15
      micrograms/ml of ceftibuten. The ceftibuten PAE was not affected by serum. The
      ceftibuten PAE was prolonged by exposure to a sub-minimum inhibitory
      concentration concentration of ceftibuten as would occur in the clinical
      situation. The PAE of ceftibuten was not affected by the copresence of
      erythromycin as would occur when treating infections in which atypical organisms
      are suspected. There was no correlation between bacterial reduction in colony
      forming units and the duration of PAE. A level of 6 micrograms/ml of ceftibuten
      had a similar bacterial killing activity compared with a 6-hour exposure to 15
      micrograms/ml of ceftibuten against S. pneumoniae, H. influenzae and M.
      catarrhalis. This study suggests that ceftibuten can be administered orally, once
      daily in an adult dose of 400 mg or a pediatric dose of 9 mg/kg, to treat
      respiratory infections caused by the most common pathogens.

PMID- 7567316
TI  - Ceftibuten: minimal inhibitory concentrations, postantibiotic effect and beta
      lactamase stability--a rationale for dosing programs.
AB  - Ceftibuten, a new orally absorbed cephalosporin with a novel side chain, has
      broad in vitro activity against most of the important respiratory pathogens
      including Streptococcus pneumoniae and both beta-lactamase-negative and beta
      lactamase-positive Haemophilus influenzae and Moraxella (Branhamella)
      catarrhalis. Furthermore it has high activity against Enterobacteriaceae, which
      contain classic TEM-1 beta-lactamases and those containing the new extended
      spectrum beta-lactamases, which hydrolyze parenteral third generation
      cephalosporins. Studies have shown that ceftibuten has a postantibiotic effect
      comparable to that of other beta-lactams against S. pneumoniae, H. influenzae and
      M. catarrhalis. Blood levels achieved after a single 400-mg dose given once daily
      or 9 mg/kg/day taken once daily for children yield blood levels and
      postantibiotic inhibition for the majority of a dosing period. The in vitro and
      pharmacokinetic data can be correlated to provide reasonable dosing programs for
      the new oral cephalosporins.

PMID- 7567317
TI  - Pharmacokinetics of ceftibuten in children.
AB  - The bioavailability and pharmacokinetics of ceftibuten administered as an oral
      suspension were characterized by several studies in young healthy male adults (19
      to 39 years old) and children ranging in age from 6 months to 17 years.
      Ceftibuten suspension was found to be bioequivalent and thus interchangeable with
      a standard 400-mg capsule. As with the capsule formulation, food slightly (< 20%)
      affected the rate and extent of absorption of the suspension. The recommended
      dose of 9.0 mg/kg was found to produce comparable plasma concentrations in
      children of all ages (6 months to 17 years). The range of mean values of maximum
      plasma concentrations (Cmax) was 12 to 16 micrograms/ml at the 9.0-mg/kg dose
      level. Doses of 4.5, 9.0 and 13.5 mg/kg produced Cmax and area under the plasma
      concentration-time curve values that were dose-proportional. The half-life (t1/2)
      was essentially independent of age and dose, ranging from 2 to 3 hours. The
      apparent clearance (Cl/F), uncorrected for the fraction of drug absorbed (F), is
      independent of dose but appears to increase with a decrease in age. This also
      occurs to a lesser degree with the volume of distribution (Vd/F), uncorrected for
      F. Current evidence suggests that this is more likely to be caused primarily by a
      decrease in F than an increase in Cl. Ceftibuten rapidly and extensively reaches
      the middle ear fluid in children with acute otitis media. Within 4 hours
      concentrations in middle ear fluid are similar to plasma concentrations and can
      be measured for 12 hours. The ratio of area under the concentration time curve
      for middle ear fluid relative to plasma was about 70%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7567318
TI  - Phenylketonuria screening: effect of early newborn discharge.
AB  - OBJECTIVE: To determine the percentage of term newborns discharged by 24 hours of
      life and the actions taken by physicians and institutions to avoid false-negative
      phenylketonuria (PKU) screens in these infants. DESIGN: Descriptive cross
      sectional survey. PARTICIPANTS: One hundred forty term nurseries and 157
      pediatricians. SELECTION PROCEDURE: Stratified sampling techniques were used to
      sample nurseries from the 1992 American Hospital Association guide to provide
      equal representation of each region of the country. Pediatricians were
      systematically sampled from a national list of practicing pediatricians supplied
      by Ross Laboratories to provide equal sampling from each state. RESULTS: The
      response rates were 95% (n = 133) for term nurseries and 83% (n = 131) for
      pediatricians. Twenty-four percent of healthy newborns are discharged by 24 hours
      of life. Ninety-three percent of nurseries screen all infants for PKU before
      discharge. In states without laws mandating rescreening, only 48% of institutions
      that discharge the majority of their infants (> 50%) by 24 hours of life
      rescreen. Also, in states without rescreening laws, 64% of pediatricians
      rescreen. The timing of this repeat screen ranges from less than 72 hours of life
      to 4 weeks. Determining which infants to rescreen varies by practitioner; some
      rescreen all infants, whereas others rescreen those discharged early. Just more
      than half of all pediatricians, whether practicing in a state requiring repeat
      PKU screening, claim to be familiar with the American Academy of Pediatrics
      recommendations regarding repeated PKU screening of infants discharged by 24
      hours of life. CONCLUSION: Twenty-four percent of term newborns in the United
      States are discharged by 24 hours of life. Most hospitals screen all infants for
      PKU before discharge regardless of age. The majority of states do not mandate
      rescreening; rescreening policies among pediatricians and institutions in those
      states vary widely. A significant number of infants do not receive repeated
      screening and are therefore at risk for delayed or missed diagnosis of PKU
      because of insensitive initial screens. Pediatrician awareness of the need to
      perform repeated PKU screens on infants discharged by 24 hours is poor.

PMID- 7567319
TI  - Cost-effectiveness analysis of a rotavirus immunization program for the United
      States.
AB  - OBJECTIVE: To estimate the economic consequences in the United States of routine
      childhood immunization of children younger than 1 year of age with a rotavirus
      (RV) vaccine. DESIGN: Cost-effectiveness analysis of a national RV immunization
      program from the perspective of the health care system and the perspective of
      society. Estimates of disease incidence, medical expenditures, productivity
      costs, vaccine efficacy, and vaccine coverage rates were derived from published
      literature and unpublished vaccine trial reports. The impact of changes in
      estimates of vaccine efficacy and medical costs was determined by sensitivity
      analysis. MAIN OUTCOME MEASURES: Incremental cost effectiveness, expressed as
      savings per case of RV diarrhea prevented. RESULTS: Given a vaccine efficacy rate
      of 50% and a vaccine cost of $30 per dose, an RV immunization program would
      prevent more than 1 million cases of RV diarrhea, 58,000 hospitalizations, and 82
      deaths per year. A vaccine program would cost $243 million per year but would
      yield net savings of $79 million from the perspective of the health care system
      and $466 million from the perspective of society. The incremental cost
      effectiveness was a savings of $459 per case prevented from the societal
      perspective and $78 per case prevented from the health care system perspective.
      Sensitivity analyses substantiated net savings over a wide range of variables,
      and cost effectiveness increased with greater vaccine efficacy or decreased
      vaccine cost. CONCLUSIONS: Economic and disease reduction benefits would be
      realized from the use of an RV vaccine that is partially protective against
      severe RV diarrhea. These findings suggest that immunization with an RV vaccine
      would be cost effective and cost saving.

PMID- 7567320
TI  - Pediatric residents' continuity clinics: how are we really doing?
AB  - The Accreditation Council for Graduate Medical Education (ACGME) established
      guidelines in 1989 requiring pediatric residents to attend a continuity clinic
      (CC) one half-day per week. OBJECTIVE. To assess pediatric residents' CCs, with
      an emphasis on those factors potentially affecting house staff education and
      patient care. DESIGN AND PARTICIPANTS. A multi-item questionnaire designed to
      assess the educational, administrative, and clinical components of CCs was
      distributed to all US CC directors. RESULTS. Responses were received from 164
      programs (74.9%), which represented more than 90% of all house staff in
      accredited US pediatric programs. Fifty-five percent of programs acknowledged non
      ACGME-approved exemptions from attendance, and 64% changed CC schedules dependent
      on in-patient rotation assignment. Less than half of the programs had core
      curricula or didactic conferences. Most programs (76%) were located in hospital
      clinics. Clinic resources and equipment were often limited; faculty preceptors
      and nursing and clerical support staff were frequently insufficient in number. On
      average, PL1s saw four patients per session, whereas PL2s and PL3s saw five.
      Continuity of care for the patient for phone calls, acute and after-hours visits,
      and hospitalization was limited. Directors' perceived support for CCs'
      educational programs ranged from a high of 87% by generalists to a low of 33% by
      intensivists. CONCLUSIONS. Despite the ACGME directives, many residency programs
      have not provided the required priority, protected time, or adequate resources
      for CCs. The recent emphasis on health care reform and primary care medical
      education highlights the prominent role the CC should play as an important site
      in our teaching of longitudinal and ambulatory medicine. Departmental support and
      committed resources necessary to enhance the experience and to meet the
      educational challenge successfully will be required.

PMID- 7567322
TI  - Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage
      targeted glucocerebrosidase.
AB  - OBJECTIVES: Reversal of the hematologic and visceral abnormalities characteristic
      of Gaucher disease, the most common lipid storage disorder, with biweekly
      infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well
      documented. The extent to which the skeleton responds to enzyme replacement
      therapy has not been systematically investigated. METHODS: To assess the skeletal
      response to enzyme replacement therapy, we treated 12 patients with type 1
      Gaucher disease, who had intact spleens, with macrophage-targeted
      glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2
      weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body
      weight every 2 weeks, each for 9 months. RESULTS: The lipid composition of bone
      marrow, determined by direct chemical analysis, began to improve after 6 months
      of treatment at a time when noninvasive imaging studies showed no significant
      changes. By 42 months, improvement in marrow composition was demonstrable on all
      noninvasive, quantitative imaging modalities (magnetic resonance score,
      quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in
      this study. Quantitative chemical shift imaging, the most sensitive technique,
      demonstrated a dramatic normalization of the marrow fat content in all patients.
      Net increases in either cortical or trabecular bone mass, as assessed by combined
      cortical thickness measurements and dual-energy quantitative computed tomography,
      respectively, occurred in 10 patients. CONCLUSIONS: Prolonged treatment over 3
      1/2 years with macrophage-targeted glucocerebrosidase produces objective reversal
      of disease in both the axial and appendicular skeleton in patients with Gaucher
      disease. Marked improvement occurs in marrow composition and bone mass in both
      children and adults.

PMID- 7567321
TI  - Pediatric office-based smoking intervention: impact on maternal smoking and
      relapse.
AB  - OBJECTIVE: To determine the impact of a brief smoking intervention delivered by
      pediatricians in the context of usual well baby office visits on postnatal
      maternal smoking and relapse. SETTING: Forty-nine private pediatric practices
      including 128 practitioners. DESIGN: Randomization of pediatric practices into
      minimal and extended intervention sites with all enrolled mothers of newborns
      within a practice receiving the same level of intervention. INTERVENTION: Smoking
      mothers in minimal condition received a hospital packet containing written
      information about passive smoking and a letter advising them to quit. Those in
      extended condition received the hospital packet plus oral and written advice at
      usual well baby visits: 2 weeks, 2, 4, and 6 months. MEASUREMENTS: Smoking and
      relapse rates at 6 months postpartum, demographics associated with smoking
      status, attitudes, and knowledge in regard to passive smoking, and recall surveys
      of mothers in regard to receiving advice or written materials. RESULTS: Two
      thousand nine-hundred-one mothers of newborns were enrolled in the study. Those
      in the extended condition had higher quit rates (5.9% vs 2.7%, P < .01) and lower
      relapse rates (45% vs 55%, P < .01) than those in the minimal condition. Mothers'
      educational status and the presence of a smoking partner in the home were the
      major demographic variables associated with smoking status at enrollment and at
      follow-up. Compared with smokers in the minimal condition, those in extended at 6
      months postpartum had significantly better attitudes and knowledge regarding
      passive smoking and allowed less smoking in the home. Mothers attending extended
      practices reported much higher rates of receiving oral advice and written
      materials than those in the minimal condition. CONCLUSIONS: A brief program can
      lead to major increases in the willingness of pediatricians to deliver smoking
      advice. A 1- to 2-minute intervention delivered in the context of usual well baby
      care can have a positive impact on maternal smoking and especially upon relapse
      prevention. A recent smoking history should be obtained from all mothers of
      newborns so that interventions can be aimed at both cessation and relapse
      prevention.

PMID- 7567323
TI  - Patterns of care received by Medicaid recipients with urinary tract infections.
AB  - BACKGROUND: Urinary tract infections (UTIs) occur commonly in children and may
      lead to substantial morbidity. Most experts recommend urine cultures for
      diagnosing UTIs in children. In addition, most experts recommend imaging studies
      in a portion of children diagnosed with UTIs. PURPOSE: The purpose of this study
      was to assess how rates of performance of urine cultures and imaging studies for
      children in the Alabama Medicaid program diagnosed with a UTI vary by patient
      demographics, provider characteristics, and service locations. METHODS: The study
      design was a retrospective review of Alabama Medicaid claims data. Children were
      included as UTI cases if they had a Medicaid claim for urinary tract infections
      during 1991, were continuously enrolled in Medicaid for that year, and were
      younger than 8 years of age. Claims were grouped into episodes of care, and
      episodes were assigned to a diagnosing physician. Physician locations were
      classified as rural, suburban, or urban using demographic data. Specific
      laboratory and imaging procedures were identified using CPT codes (Physician's
      Current Procedural Technology Codes, 4th Edition). RESULTS: We identified 404
      episodes of UTI occurring in 380 children. Only 47% of episodes were associated
      with claims for urine cultures. Claims for urine cultures were more frequently
      filed by pediatricians in urban locations. In the subset of 114 patients with
      multiple UTI episodes, only 68% had imaging studies specific for the urinary
      tract. Only 44% received both a voiding cystourethrogram and renal ultrasound.
      CONCLUSIONS: Claims data suggest that physicians underuse urine cultures in
      diagnosing UTIs in Alabama pediatric Medicaid recipients. Urban-based
      pediatricians perform better than other types of physicians. Imaging studies are
      also used less frequently than is commonly recommended.

PMID- 7567324
TI  - Development of a population-specific risk assessment to predict elevated blood
      lead levels in Santa Clara County, California.
AB  - OBJECTIVES: To determine: (1) the prevalence of a blood lead level (PbB) of 10
      micrograms/dL or greater and 20 micrograms/dL or greater among children aged 6 to
      72 months attending the Santa Clara County (SCC), California, public clinics, (2)
      risk factors for elevated PbB in this population, and (3) whether an SCC public
      clinic population-specific risk-assessment tool and a five-question lead
      poisoning questionnaire developed by the Centers for Disease Control and
      Prevention are useful for prospectively identifying children at higher risk for
      elevated PbB. METHODS: We tested for PbB 3630 children aged 6 to 72 months
      attending SCC public outpatient clinics between August 8, 1991, and September 1,
      1992. We then conducted two matched case-control studies. Five local risk-factor
      questions were combined with the CDC's five-question lead poisoning
      questionnaire, and from May 1, 1993, to June 30, 1993, we conducted risk
      assessments on 247 children tested for PbB. RESULTS: Two hundred twenty-two of
      3630 children (6.1%) had a PbB of 10 micrograms/dL or greater. Thirty-nine (1.1%)
      had a PbB at least 20 micrograms/dL. Seventy-nine percent of the children
      screened and 91.0% of the children with PbB at least 10 micrograms/dL were
      Hispanic. Twenty percent of Mexican-born Hispanic children had a PbB of 10
      micrograms/dL or greater, versus 7% of U.S.-born Hispanic children. Several
      factors were associated with elevated PbB among Hispanic children. For
      identifying children with a PbB of at least 10 micrograms/dL, the sensitivity and
      predictive value negative for the CDC's "high risk" definition were 30% and 93%,
      respectively, whereas for the SCC population-specific high-risk definition, the
      sensitivity was 90% and the predictive value negative was 98%. CONCLUSIONS:
      Hispanic children attending SCC public clinics have risk factors for elevated PbB
      that were not included in the CDC's lead poisoning questionnaire. Methods for
      prioritizing the frequency of lead screening may be improved by combining the
      CDC's questions with a population-specific risk assessment.

PMID- 7567326
TI  - Aerobic response to endurance exercise training in children.
AB  - OBJECTIVE: To investigate the ability of children to improve aerobic fitness, as
      indicated by changes in maximaal oxygen uptake (VO2max), after a 12-week period
      of endurance training. DESIGN: Longitudinal prospective training with control
      period. SETTING: Middle school physical education class. SUBJECTS: Twenty-four
      girls and 13 boys, ages 10.9 to 12.8 years. INTERVENTION: Three 30-minute
      sessions of aerobic activity weekly for 12 weeks at an intensity-producing a mean
      heart rate of 166 beats per minute. Maximal treadmill testing was performed 12
      weeks before the training program and again at the start and end because each
      child served as his/her own control. RESULTS: Mean VO2max did not change
      significantly during the control period but rose from 44.7 (5.8) to 47.6 (6.4) mL
      kg-1min-1 (6.5%) with training (P < .05). No differences in training response
      were observed relative to sex, pretraining VO2max, or sports participation.
      CONCLUSION: These findings support the concept that VO2max can be improved with
      endurance training during the childhood years, but the degree of aerobic train
      ability is limited in healthy, active children.

PMID- 7567325
TI  - Parents' attitudes toward firearm injury prevention counseling in urban pediatric
      clinics.
AB  - OBJECTIVES: To examine characteristics and experiences associated with gun
      ownership among parents of pediatric patients who attend urban pediatric clinics
      and to determine the receptivity of these parents to firearm injury prevention
      counseling. DESIGN: A focus group discussion was followed by a cross-sectional
      survey. SETTING: Four public pediatric clinics in a large metropolitan area were
      included. PARTICIPANTS: A focus group discussion was held with parents and was
      used to develop the questionnaire, which was then distributed over a 6-week
      period to parents accompanying children to the clinic. The anonymous, self
      administered questionnaire was completed by 510 parents or guardians, with an 88%
      response rate. RESULTS: Twenty percent of respondents reported that they had a
      firearm in the home. Twenty-seven percent of respondents had experienced having a
      family member shot. Eighty-two percent of all respondents indicated that they
      would find information about the safest way to store a gun helpful or very
      helpful. Of all respondents, 47% would follow and an additional 37% would think
      over a provider's advice not to keep guns in the home. Gun owners were less
      inclined to report that they would follow this advice (19%), but 55% of the gun
      owners would think over this advice. Only 6% of all respondents reported that
      they would ignore or be offended by such advice. CONCLUSIONS: Children attending
      public urban pediatric clinics are exposed to guns in their homes, and their
      parents appear to be receptive to firearm injury prevention counseling from their
      child's health care providers.

PMID- 7567327
TI  - Association between postpartum substance use and depressive symptoms, stress, and
      social support in adolescent mothers.
AB  - OBJECTIVE: Substance use by pregnant teenagers is an important public health
      problem, but published data on alcohol and illicit drug use by parenting
      teenagers are virtually nonexistent. This study determined the prevalence of
      alcohol and drug use in adolescent mothers in the first 4 months postpartum and
      explored associated psychosocial characteristics. METHODS: Teenagers attending a
      comprehensive adolescent pregnancy and parenting program were enrolled
      consecutively during a routine third trimester prenatal visit. Alcohol use since
      delivery was determined by self-report at 4 months postpartum using an instrument
      developed for the 1984 Survey of Drug Abuse Among Maryland Adolescents. Illicit
      drug use was measured with anonymous quantitative urine drug screens at 2 and 4
      months postpartum. Depressive symptoms, stress, and social support were assessed
      at 2 and 4 months postpartum using validated, self-administered instruments.
      Differences in demographic characteristics, peer group influences, and
      psychosocial variables between substance users and nonusers were evaluated.
      RESULTS: Participants (125/129 eligible) were predominantly African-American,
      mean age 16.3 years. Completed assessments were obtained from 110 at 2 months and
      105 at 4 months postpartum. Forty-two percent screened positive for illicit drugs
      at a postpartum visit or reported using alcohol since delivering their baby and
      were classified as substance users. Thirty-one percent of subjects reported
      alcohol use since delivery. Marijuana was the most prevalent illicit drug (14%),
      followed by opiates (5%), and cocaine (4%). When substance users were compared
      with nonusers, 44% versus 24% scored depressed (P = .02), 62% versus 43% had high
      stress (P = .04), and 62% versus 44% reported a high need for social support (P =
      .07). Results of logistic regression, after controlling for age, indicated that
      illicit substance and/or alcohol use was 3.3 times greater for those who were
      depressed, 2.8 times greater if they reported friends' using illicit drugs, and
      6.7 times greater if the adolescent reported smoking cigarettes since delivery.
      CONCLUSIONS: This study indicates that alcohol and drug use are common among this
      sample of postpartum teenage mothers and that depression, stress, high support
      need, and peer group drug use are associated factors. Although this study cannot
      determine whether depression and stress precede or result from use of substances,
      attention to these factors appears warranted in the care of adolescent mothers.

PMID- 7567328
TI  - Humeral fractures without obvious etiologies in children less than 3 years of
      age: when is it abuse?
AB  - OBJECTIVE: To determine the occurrence and frequency of abuse in children with
      humeral fractures without immediately obvious etiologies who are less than 3
      years old and present with arm injuries. METHODS: A retrospective chart review
      was conducted of all children less than 3 years old treated for a humeral
      fracture at Children's Hospital Medical Center between July 1, 1990, and
      September 10, 1993. One hundred twenty-four charts of children with humeral
      fractures were reviewed for possible abuse using previously developed criteria.
      Charts were evaluated independently by the investigators. Consensus was reached
      on classification of each chart into the following categories: abuse,
      indeterminate, or not abuse. RESULTS: Abuse was diagnosed in 9 of 25 (36%)
      children less than 15 months of age, but in only 1 of 99 (1%) children older than
      15 months (P < .05). Abuse was excluded in 91 of 124 (73%) children. No
      determination of abuse (indeterminate) could be made in 23 of 124 (18.5%)
      children. In children less than 15 months of age, abuse was diagnosed in 2 of 10
      (20%) with supracondylar fractures and in 7 of 12 (58%) with spiral/oblique
      fractures. CONCLUSION: The prevalence of abuse in our children presenting with
      humeral fractures was much lower than in other published reports, especially in
      the children over the age of 15 months. However, we found a higher prevalence of
      supracondylar fractures associated with abuse than those same reports. Given
      these findings, abuse should be considered in all children less than 15 months of
      age with humeral fractures, including those with supracondylar fractures. The
      majority of humeral fractures in children are accidental, especially beyond the
      age of 15 months.

PMID- 7567329
TI  - Sex chromosome tetrasomy and pentasomy.
AB  - Sex chromosome abnormalities occur in at least 1 in 400 births and include the
      well-described 47,XXX, 47,XXY, 47,XYY, and 45,X karyotypes. The addition of more
      than one extra X or Y chromosome occurs rarely, and little information is
      available in the medical literature. Individual case reports make up most of this
      body of knowledge, and all are based on subjects who identified themselves
      postnatally. Many were ascertained through screenings of institutions and
      hospitals; thus, there is no unbiased information on the natural history of poly
      X and Y karyotypes. A direct relationship between the number of additional sex
      chromosomes and the severity of the phenotype is generally assumed. The purpose
      of this article is to summarize what is known about these conditions and to
      present 10 additional cases. The karyotypes include, 48,XXXX, 49,XXXXX, 48,XXYY,
      48,XXXY, 49,XXXXY, 49,XXXYY, 48,XYYY, 49,XYYYY, and 49,XXYYY.

PMID- 7567330
TI  - Short-term efficacy of oral dimercaptosuccinic acid in children with low to
      moderate lead intoxication.
AB  - OBJECTIVE: To determine the short-term efficacy of meso-2,3-dimercaptosuccinic
      acid (DMSA) in mild to moderately lead poisoned children. METHODS: Medical
      records of all pediatric patients receiving 19 days of DMSA between June 1991 and
      May 1993 were reviewed retrospectively. Patients were included if their
      pretreatment blood lead concentration (BPb) was 1.21 to 2.36 mumol/L (25 to 49
      micrograms/dL) and excluded if they: received DMSA through participation in a
      pharmaceutical company-sponsored drug study; underwent chelation therapy in the
      previous 28 days; or received another chelating agent concomitantly with DMSA; or
      if noncompliance was documented. Homes were inspected and abated of major hazards
      before chelation therapy. BPb and blood zinc protoporphyrin concentration (ZnP)
      were obtained at baseline. DMSA was administered in a dose approximating 10 mg/kg
      per dose every 8 hours for 5 days, followed by 10 mg/kg per dose every 12 hours
      for 14 days. Baseline laboratory studies were repeated weekly while the patients
      were receiving therapy and for 2 weeks after therapy, then monthly unless
      chelated again. RESULTS: Of the 46 children who were treated with DMSA, 18 were
      excluded from the analysis. In the remaining 28 children, the mean +/- SD
      pretreatment BPb and ZnP were 1.79 +/- 0.33 mumol/L (37 +/- 6.9 micrograms/dL)
      and 1.26 +/- 0.64 mumol/L (71 +/- 36.1 micrograms/dL), respectively. The percent
      reduction (mean +/- SD) in BPb compared with baseline was -43% +/- 20.8%, -26% +/
      16.9%, and -31% +/- 20.2% on mean days 18, 30, and 80, respectively, whereas the
      changes in ZnP were -12% +/- 21.7%, -20% +/- 18.1%, and -31% +/- 21.9%,
      respectively. Eighty percent of patients had 20% or more reduction in their
      pretreatment BPb and/or ZnP after completion of DMSA therapy (95% confidence
      interval, 61, 92%). No significant adverse effects were observed except for
      neutropenia (absolute neutrophil count of 0.752 x 10(9)/L) in one patient.
      CONCLUSION: Our findings support the short-term efficacy of DMSA in children with
      BPb of 2.36 mumol/L (49 micrograms/dL) or less.

PMID- 7567331
TI  - Surface electrical capacitance as a noninvasive bedside measure of epidermal
      barrier maturation in the newborn infant.
AB  - OBJECTIVE: The classical studies of epidermal barrier function in infants have
      relied on measurement of transepidermal water loss by evaporimetry. This
      technique, although valuable, is, in practice, slow, expensive, and susceptible
      to error because of convective air currents. In this prospective study, we
      evaluated gestation-dependent and postnatal age-dependent changes in epidermal
      barrier function by measurement of skin surface electrical capacitance (SEC) in
      40 newborn infants ranging from 25 to 40 weeks' gestational age. SEC was measured
      in picofarads with a dermal phase meter. METHODOLOGY: The measurements were
      recorded continuously during a 12-second period from the forehead at 12 to 24
      hours of life. The baseline (CBL) surface hydration at 1 second and the rate of
      change of SEC during probe occlusion (CSL) were used as measures of surface
      hydration and transepidermal water movement, respectively. In the most premature
      infants (< 30 weeks), these measurements were repeated daily for 5 days. Data
      were analyzed by analysis of variance after logarithmic (Ln) transformation.
      RESULTS: We found a significant difference in Ln(CBL) in infants born before and
      after 30 weeks' gestation (4.91 +/- 0.36 Ln[pF] vs 2.67 +/- 0.21 Ln[pF],
      respectively). Similarly, CSL was significantly different in infants born before
      and after 30 weeks' gestation (16.42 +/- 5.55 pF/s vs 1.59 + 0.22 pF/s,
      respectively). In infants born at less than 27 weeks, both Ln(CBL) and CSL
      decreased significantly by postnatal day 5. In the term group (n = 25), CSL was
      significantly greater in white than in black infants (1.96 +/- 1.32 pF/s vs. 0.95
      +/- 0.55 pF/s, respectively). CONCLUSION: These results demonstrate impaired
      epidermal barrier properties in immature infants, less than 30 weeks' gestation,
      and reveal a remarkable rate of barrier maturation of this group in the first few
      days of postnatal life. Also, the finding of decreased CSL in black infants
      supports the hypothesis of differences in barrier function attributable to skin
      types. Overall, these findings demonstrate the feasibility of bedside SEC
      measurements in the evaluation of epidermal barrier properties in the newborn
      infant.

PMID- 7567333
TI  - Gastrostomy tube supplementation for HIV-infected children.
AB  - OBJECTIVE: Malnutrition is common in pediatric human immunodeficiency virus (HIV)
      infection, and little is known of effective nutritional interventions. We sought
      to determine whether enteral supplementation with gastrostomy tube feedings would
      provide improvements in weight, height, body composition, immune parameters,
      morbidity, and mortality. METHODS: We collected clinical data on 23 HIV-infected
      children who were fed chronically by gastrostomy tube. The main outcome measures
      included weight, height, triceps skinfold thickness (TSF), arm-muscle
      circumference (AMC), hospital days, caloric intake, and CD4-positive T-lymphocyte
      count. Each of these parameters was measured or evaluated at four points: 6
      months before nasogastric tube feeding, at the time nasogastric tube feeding was
      initiated, at the time gastrostomy tube feeding was initiated, and 6 months after
      gastrostomy tube feedings began. RESULTS: Weight z score [-2.1 (0.14) to -1.58
      (0.14)] and weight-for-height z score [-0.98 (0.16) to -0.15 (0.17)] improved
      with gastrostomy tube feedings. There was a trend toward improvement in weight z
      score with nasogastric tube feedings. Caloric intakes increased progressively
      with nasogastric and gastrostomy tube feedings. No improvement in height, TSF,
      AMC, hospital days, or CD4 counts was seen in the follow-up period. However,
      children who had the greatest increase in weight had the most improvement in fat
      stores (TSF) (r = .65, P = .002) and a decrease in hospital days after the
      gastrostomy tube was placed (r = -.48, P = .025). Higher age-adjusted CD4 counts
      and lower weight-for-height z scores at the time of enteral supplementation were
      significant predictors of a positive response to gastrostomy tube feedings (r =
      .85, P = .0001). Children who responded favorably had a 2.8-fold reduction in the
      risk of dying for every positive unit change in weight z score (P = .005).
      CONCLUSION: Gastrostomy tube supplementation for HIV-infected children can
      improve weight and fat mass when other oral methods fail. Weight gain is
      coincident with greater caloric intakes. HIV-infected children with higher CD4
      counts and lower weight-for-height z scores are likely to respond favorably to
      gastrostomy tube feedings. Early nutritional intervention is indicated for HIV
      infected children.

PMID- 7567334
TI  - Technology assessment of nonsurgical closure of patent ductus arteriosus: an
      evaluation of the clinical effectiveness and costs of a new medical device.
AB  - OBJECTIVE: To assess the clinical efficacy and cost impact of a new medical
      device for the nonsurgical closure of patent ductus arteriosus (PDA). METHODS:
      This was a before-after study comparing the most recent 20 surgical procedures
      with the first 20 nonsurgical procedures for PDA using a new medical device.
      Clinical outcome, hospital stay, device cost, and physician fees were compared.
      RESULTS: Surgical closure was effective in all 20 patients, with an average cost
      of $4667. In a similar patient group, nonsurgical closure was achieved in 18 of
      20 patients (90%), with an estimated average cost per successful procedure of
      $4690. A clinically insignificant PDA leak persisted beyond 12 months in four
      nonsurgically managed patients. CONCLUSION: Nonsurgical closure of PDA can be
      recommended as an effective new medical technique that is not associated with a
      measurable increase in direct costs and that provides significant indirect and
      intangible cost advantages.

PMID- 7567335
TI  - Parental stress and growth outcome in growth-deficient children.
AB  - OBJECTIVE: In order to examine the relationship between parental stress, child
      psychosocial factors, anemia, lead poisoning, and growth deficiency (GD), 48
      children attending a GD referral program were recruited consecutively and matched
      with 50 comparison subjects from a primary care program. METHOD: Parents
      completed the Parenting Stress Index (PSI) with subscales and provided
      demographic data. Children received developmental screening, hemoglobin levels,
      Pb levels, and growth evaluation. They also received medical evaluation for GD. T
      tests were used to evaluate group differences. Spearman Rho correlation analyses
      were computed between group coefficients and PSI scales, Pb, and hemoglobin
      levels. RESULTS: No differences were found on the PSI with regard to overall
      parental stress. GD parents perceived themselves as less competent (P < .001),
      and their children as less adaptable (P < .006). They also reported more social
      isolation (P < .05). The GD group had more anemia and Pb poisoning (P < .002 and
      P < .001, respectively); however, these variables were not related to differences
      in child adaptability or growth outcome. A high sense of parental competence and
      high child adaptability were associated with improved growth outcomes (P < .001
      and P < .02, respectively). CONCLUSIONS: We conclude that parents of GD children
      seen in an outpatient referral setting show no difference in overall perceived
      stress levels versus comparison subjects. Increased parental competence and child
      adaptability are strongly associated with improved growth outcome. Decreased
      child adaptability may contribute to GD pathology. These findings challenge the
      traditional view of GD etiology.

PMID- 7567332
TI  - Chemotherapy plays a major role in the inhibition of catch-up growth during
      maintenance therapy for childhood acute lymphoblastic leukemia.
AB  - OBJECTIVE: In children treated for acute lymphoblastic leukemia (ALL), catch-up
      growth occurs after cessation of therapy and not during maintenance therapy. In
      this study we investigated whether this inhibition of catch-up growth during
      maintenance treatment is attributable to the influence of chemotherapy or to the
      influence of corticosteroids. PATIENTS: Forty-six children treated for ALL were
      included in the study. In 27 patients maintenance therapy comprised vincristine
      (VCR), prednisone (Pred), or dexamethasone (Dexa) alternated with 6
      mercaptopurine (6-MP) and methotrexate (MTX) and 19 patients received maintenance
      therapy with 6-MP and MTX only. Treatment did not include cranial irradiation.
      RESULTS: Statural growth during maintenance treatment was comparable in both
      groups over the study period of 1.5 years. CONCLUSION: Chemotherapy with 6-MP and
      MTX, and not corticosteroids, is the main factor that prevents catch-up growth
      from occurring during maintenance therapy for ALL.

PMID- 7567336
TI  - Managing otitis media: a time for change.
AB  - Given the increasing prevalence of multiply resistant pneumococcal infection and
      the heightened risks associated with antimicrobial usage, antimicrobial treatment
      of otitis media in children should be restricted generally to the extent possible
      without compromising individual children's well-being and without subjecting them
      to risks potentially greater than the risks associated with antimicrobial usage.
      Not infrequently the decisions required will be difficult and matters of
      judgment. However, in most cases the indications for initiating or prolonging
      antimicrobial treatment will be either straightforward, calling for a decision to
      proceed, or marginal, in which case the decision not to proceed should be clear.

PMID- 7567339
TI  - Kernicterus in otherwise healthy, breast-fed term newborns.
AB  - OBJECTIVE: To document the occurrence of classical kernicterus in full-term,
      otherwise healthy, breast-fed infants. METHODS: We reviewed the files of 22 cases
      referred to us by attorneys throughout the United States during a period of 18
      years, in which neonatal hyperbilirubinemia was alleged to be responsible for
      brain damage in apparently healthy, nonimmunized, full-term infants. To qualify
      for inclusion, these infants had to be born at 37 or more weeks' gestation,
      manifest the classic signs of acute bilirubin encephalopathy, and have the
      typical neurologic sequelae. RESULTS: Six infants, born between 1979 and 1991,
      met the criteria for inclusion. Their peak recorded bilirubin levels occurred 4
      to 10 days after birth and ranged from 39.0 to 49.7 mg/dL. All had one or more
      exchange transfusions. One infant had an elevated reticulocyte count (9%) but no
      other evidence of hemolysis. The other infants had no evidence of hemolysis, and
      no cause was found for the hyperbilirubinemia (other than breast-feeding).
      CONCLUSIONS: Although very rare, classic kernicterus can occur in apparently
      healthy, full-term, breast-fed newborns who do not have hemolytic disease or any
      other discernible cause for their jaundice. Such extreme elevations of bilirubin
      are rare, and we do not know how often infants with similar serum bilirubin
      levels escape harm. We also have no reliable method for identifying these infants
      early in the neonatal period. Closer follow-up after birth and discharge from the
      hospital might have prevented some of these outcomes, but rare, sporadic cases of
      kernicterus might not be preventable unless we adopt an approach to follow-up and
      surveillance of the newborn that is significantly more rigorous than has been
      practiced. The feasibility, risks, costs, and benefits of this type of
      intervention need to be determined.

PMID- 7567338
TI  - Hospital readmission due to neonatal hyperbilirubinemia.
AB  - Severe neonatal hyperbilirubinemia can occur without apparent reason in term
      healthy breast-fed infants and some develop kernicterus. The aim of our study was
      to assess the incidence of severe hyperbilirubinemia in term healthy newborns
      discharged from the hospital. From January 1 through December 31, 1994, 6705
      infants were delivered at Bikur-Cholim and Misgav-Ladach Community Hospitals. All
      1448 newborns discharged with a serum bilirubin level > 10.0 mg/dL were
      instructed to return to the hospital within 3 days for follow-up, as well as
      bilirubin determination. Twenty-one newborns with a bilirubin level > 18.0 mg/dL
      were identified and readmitted at mean +/- standard deviation (SD) 5.5 +/- 1.8
      (range, 5 to 10 days of life). This represents 1.7% of the 1220 infants who
      returned for follow-up examination. Mean +/- SD serum bilirubin levels at
      readmission were 19.6 +/- 2.5 mg/dL. All but one of the infants were breast-fed.
      No cases of ABO incompatibility were found and two newborns were glucose-6
      phosphate dehydrogenase (G6PD)-deficient. Sepsis work-up and direct Coomb's tests
      were negative in all cases. None had hemolysis or were found to have any cause
      for hyperbilirubinemia other than breast-feeding. Phototherapy was provided in
      all but two cases, and an exchange transfusion was performed in one case. Three
      additional infants, with bilirubin levels < 10 mg/dL at discharge, were
      readmitted due to hyperbilirubinemia. One was diagnosed with neonatal hepatitis.
      We conclude that, based on our study population, 0.36% of term infants may
      subsequently develop severe neonatal hyperbilirubinemia in the first postnatal
      week.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567337
TI  - Problems associated with early discharge of newborn infants. Early discharge of
      newborns and mothers: a critical review of the literature.
AB  - OBJECTIVE: To determine whether research supports the advisability of early
      discharge of healthy newborns and mothers. METHODS: Critical review of English
      language literature cited in the Index Medicus or the International Nursing
      Index. FINDINGS: No adequately designed studies have examined discharge before 48
      hours after delivery without additional postdischarge services. Few studies have
      examined the consequences of recommending a clinic visit within the first days
      after discharge; studies of this practice among low-income populations found high
      no-show rates. Some small studies suggest that early discharge is likely to be
      safe for selected populations at low psychosocial, socioeconomic, and medical
      risk, with careful antenatal screening and preparation and multiple postpartum
      home visits. Some studies suggested adverse outcomes associated with early
      discharge even with early follow-up. CONCLUSIONS: Published research provides
      little knowledge of the consequences of short maternal/newborn hospital stays or
      varying postdischarge practices for the general population. The studies that have
      concluded that early discharge was safe were applied under restricted
      circumstances or were too small to detect clinically significant effects on
      important outcomes. Further research is needed to inform clinical and
      reimbursement policy on health services in the first days of life and parenting.
      Rigorous studies of sufficient size are needed to examine the impact of different
      hospital stays and different postdischarge practices on a range of outcomes for
      mothers and newborns in diverse populations and settings. Given a priori
      concerns, decisions on neonatal/obstetric discharge planning should be made
      cautiously.

PMID- 7567341
TI  - Early discharge: in the end, it is judgment.

PMID- 7567340
TI  - Hidden risks: early discharge and bilirubin toxicity due to glucose 6-phosphate
      dehydrogenase deficiency.

PMID- 7567342
TI  - Summary of workshop: early discharge and neonatal hyperbilirubinemia.

PMID- 7567343
TI  - Early discharge, in the end: maternal abuse, child neglect, and physician
      harassment.

PMID- 7567345
TI  - Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a
      statement for health professionals. Committee on Rheumatic Fever, Endocarditis,
      and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the
      American Heart Association.
AB  - Primary prevention of acute rheumatic fever is accomplished by proper
      identification and adequate antibiotic treatment of group A beta-hemolytic
      streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best
      accomplished by a throat culture. Penicillin (either oral penicillin V or
      injectable benzathine penicillin) remains the treatment of choice, because it is
      cost effective, has a narrow spectrum of activity, has long-standing proven
      efficacy, and GAS resistant to penicillin have not been documented. Various
      macrolides, oral cephalosporins, and other beta-lactam agents are acceptable
      alternatives, particularly in penicillin-allergic individuals. The individual who
      has had an attack of rheumatic fever is at very high risk of developing
      recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial
      prophylaxis to prevent such recurrences (secondary prevention). The duration of
      prophylaxis depends on the number of previous attacks, the time lapsed since the
      last attack, the risk of exposure to streptococcal infections, the age of the
      patient, and the presence or absence of cardiac involvement. Penicillin is again
      the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin
      are acceptable alternatives in penicillin-allergic individuals. This report is an
      update of a 1988 statement by this committee. It expands on the previous
      statement, includes more recent therapeutic modalities, and makes more specific
      recommendations for the duration of secondary prophylaxis.

PMID- 7567344
TI  - What's new in pediatric surgery.

PMID- 7567346
TI  - Recommended guidelines for uniform reporting of pediatric advanced life support:
      the pediatric Utstein style. A statement for healthcare professionals from a task
      force of the American Academy of Pediatrics, the American Heart Association, and
      the European Resuscitation Council.
AB  - This consensus document is an attempt to provide an organized method of reporting
      pediatric ALS data in out-of-hospital, emergency department, and in-hospital
      settings. For this methodology to gain wide acceptance, the task force encourages
      development of a common data set for both adult and pediatric ALS interventions.
      In addition, every effort should be made to ensure that consistent definitions
      are used in all age groups. As health care changes, we will all be challenged to
      document the effectiveness of what we currently do and show how new interventions
      or methods of treatment improve outcome and/or reduce cost. Only through
      collaborative research will we obtain the necessary data. For these reasons, and
      to improve the quality of care and patient outcomes, it is the hope of the task
      force that clinical researchers will follow the recommendations in this document.
      It is recognized that further refinements of this statement will be needed; these
      recommendations will improve only when researchers, clinicians, and EMS personnel
      use them, work with them, and modify them. Suggestions, emendations, and other
      comments aimed at improving the reporting of pediatric resuscitation should be
      sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital
      of The King's Daughter, Division of Critical Care Medicine, 601 Children's Lane,
      Norfolk, VA 23507.

PMID- 7567347
TI  - Isolated spinal cord injury as a presentation of child abuse.

PMID- 7567348
TI  - Water-ski douche injury in a premenarcheal female.

PMID- 7567350
TI  - Children, adolescents, and television. American Academy of Pediatrics Committee
      on Communications.

PMID- 7567349
TI  - Hepatitis in association with human herpesvirus-7 infection.

PMID- 7567351
TI  - Hospital stay for healthy term newborns. American Academy of Pediatrics Committee
      on Fetus and Newborn.

PMID- 7567352
TI  - Foley catheter and esophageal foreign bodies.

PMID- 7567353
TI  - Foley catheter and esophageal foreign bodies.

PMID- 7567354
TI  - Foley catheter and esophageal foreign bodies.

PMID- 7567355
TI  - Corporal punishment.

PMID- 7567357
TI  - Intensive care treatment decisions: the roots of our confusion.

PMID- 7567356
TI  - Corporal punishment.

PMID- 7567358
TI  - Etiology of bronchopulmonary dysplasia.

PMID- 7567359
TI  - Adapting your pediatric practice to the changing health care system.

PMID- 7567360
TI  - Pediatric Practice: How to Survive and Thrive in the Changing Health Care System.
      Proceedings of a meeting. San Diego, California, February 24-26, 1995.

PMID- 7567362
TI  - A look at the private practice of the future.
AB  - Powerful trends that have influenced pediatric care in recent decades will sweep
      us into the new century. By looking at the major forces at work today, we can
      predict where we will be 10 years from now. As infectious diseases continue to
      decline, psychosocial disorders will take a larger share of the pediatrician's
      efforts. Technology will allow more effective management, but it will require
      strong commitment to ongoing education. More children with chronic conditions and
      more young adults will fall under the care of pediatricians. Prevention will
      retain a central role in practice. Maintaining an independent practice will
      become more difficult, and a wide range of delivery schemes will emerge.
      Relationships among pediatricians and relationships with other health care
      providers will be influenced significantly by these systems, which carry
      potential for both positive and negative impact on the quality of care and on the
      lifestyles of pediatricians. It is crucial that pediatricians take an active and
      committed role in shaping the evolution of care systems, thereby making the
      future what it should be for children.

PMID- 7567361
TI  - Child health 2000: new pediatrics in the changing environment of children's needs
      in the 21st century.
AB  - Pediatric practice in the next millennium will require greater knowledge of new
      morbidities, such as acquired immunodeficiency syndrome and social and behavioral
      disorders, reemergent old disorders, such as tuberculosis, and disorders rarely
      seen of late in the United States but now being brought here by recent
      immigrants, such as malaria and other parasitic diseases. Diversity in ethnic and
      cultural backgrounds and beliefs will continue to increase, and it will need to
      be understood to prevent and treat diseases of children effectively. Although the
      current antagonism toward immigrants may lead to a decrease in this particular
      source of diversity, changes in family structure--such as divorce, gay and
      lesbian couples as parents, and corporate pressure on families--will continue,
      requiring pediatricians to understand and to accept this diversity if they are to
      be the health care providers of children. The increased isolation of individuals
      from society and separation from families of origin will require pediatricians to
      be more active in communities and schools and to participate with other
      disciplines and social support groups. At the same time, the advancement of
      science and technology will continue to drive what the pediatrician does.
      Increased survival of children who previously had fatal illnesses will mean more
      emphasis on care of children who have chronic illnesses. Pediatricians will need
      to be partners with others in the exciting new fields of risk assessment and
      prevention of psychosocial disorders.

PMID- 7567364
TI  - Clinical and behavioral adaptation to managed care: stepwise suggestions for
      survival.
AB  - The rapid growth of managed care has left many physicians concerned and often
      bewildered about the new realities of the day. Essentially, managed care is a
      euphemism for a different kind of authority, responsibility, and accountability.
      Under "unmanaged care," authority, responsibility, and accountability were gained
      from and directed toward the patient. This arrangement has been supplanted by a
      new system in which the physician derives his authority from and is responsible
      and accountable to both the patient and the managed care company. The diagnosis
      of managed care is easy enough. It is a chronic disease; it does not go away. For
      those who can make the adjustment, managed care will not end careers. Rather, it
      will require a realignment, an adaptation to the societal mandate for "value."
      With care, foresight, and professionalism, this realignment can be navigated
      successfully, and disruption in the lives of pediatricians and patients can be
      held to a minimum.

PMID- 7567365
TI  - The economic survival of pediatric practice.
AB  - Many aspects of pediatric practice in the future are unclear. Among them is how
      pediatricians will be reimbursed. Based on trends established during the past 10
      years, capitation is a likely mechanism. The advantages and disadvantages of
      capitation as a reimbursement mechanism--particularly as it compares with fee for
      service--are discussed, and a simplified description of how capitation rates are
      set is included.

PMID- 7567363
TI  - How can pediatric care be provided in underserved areas? A view of rural
      pediatric care.
AB  - Building on the concept that the future is not what it used to be, this article
      will address the delivery of primary care pediatrics in rural America. I will
      discuss the demographic differences that exist today between urban and rural
      areas, the differences in practice style and lifestyle in different geographic
      arenas, and the unique hardships created by those differences. The strengths and
      opportunities that are available now and that will be in the future will be
      reviewed. I will discuss the application of those opportunities in an attempt to
      construct a framework for a successful transition into the "new future."

PMID- 7567366
TI  - Thriving in the 21st century: outcome assessment, practice parameters, and
      accountability.
AB  - The past two decades have brought about major health care changes that have been
      driven by an ever-increasing cost of health care, practice variability, and
      medical malpractice litigation. These changes pose a challenge to pediatricians
      to contain costs, to reduce inappropriate use of health care services, and to
      demonstrate improved health care outcomes. To meet this challenge, a new
      "clinical tool kit" is required, one that will allow the pediatrician to analyze
      current practices and to document effective interventions. Two of the major tools
      in this kit are practice guidelines and outcomes assessment instruments. Practice
      guidelines are optimal care specifications that provide an analytic framework for
      defining high-quality care and measuring health care outcomes. Ideally, these
      guidelines should be developed from scientific evidence. In practice, however,
      scientific evidence to support the majority of recommendations made in guidelines
      is insufficient. Consequently, these recommendations are instead developed by
      expert consensus. Measurement of health outcomes includes clinical outcomes,
      patient satisfaction, cost and use, and quality of life. Health care
      organizations have become very sophisticated in measuring cost and use, but
      considerably less work has been done in the patient-centered areas of
      satisfaction and quality of life. This is particularly true for children, because
      measures are dependent on the viewpoint chosen (parent, child, or teacher), the
      age of the child, and the adjustment for severity of illness. Analyzing practice
      patterns and improving health outcomes will not be easy tasks to accomplish. For
      the pediatrician to use these tools in an efficient and effective manner, a new
      research agenda and new skills will be required.

PMID- 7567367
TI  - The computerization of ambulatory pediatric practice.
AB  - With the shift in pediatrics toward emphasis on preventive care and anticipatory
      guidance, especially in this era of care- and cost-management, quality care is
      becoming increasingly synonymous with good information processing. To achieve our
      maximum effectiveness as clinicians as well as business persons, because
      pediatrics is a business, we must learn to use the tool that the rest of the
      business world has long ago discovered and implemented: computerization. Most
      important, we must apply this technology not only to the business of medicine,
      but to the practice of medicine itself, for that is where our future and the
      future of our children lie. From the perspective of someone who has been there, I
      will discuss what computerized information access and information processing has
      allowed us to accomplish in practice, and I will give a glimpse of what medicine
      will be like when we all can manipulate medical information so rapidly that it
      enables us to practice true preventive care aggressively, to give anticipatory
      guidance and parent education in a timely manner, and to assess and monitor the
      progress of our children effectively.

PMID- 7567369
TI  - Les Nouveaux Miserables: modern victims of social asphyxia.
AB  - During the past 30 years, social and economic barriers to health care services
      have increased for many Americans, especially for the nation's most vulnerable
      populations. Health status actually has declined for certain populations during
      this time. Meanwhile, national attention has been focused primarily on containing
      health care costs and on devising strategies for reforming the financing of
      health care rather than strategies for achieving improvements in the health
      status of the population. Existing methods of financing health care services,
      health research priorities, the increasing centralization and
      compartmentalization of health care services, and the recent failure of national
      health reform all serve to hinder this nation's progress towards developing a
      comprehensive and accountable health care system focused on promoting and
      achieving improved health as well as treating sickness. Recent changes in the
      health care marketplace, however, including a growing movement toward measuring
      the outcomes of medical treatments and an emphasis on improving the quality of
      services, have increased interest among payers and providers of health care
      services in investing in preventive services. Health maintenance organizations
      and other integrated health care delivery systems are beginning to devise
      incentives for increasing preventive care as well as for containing costs. The
      transformation of the nation's current medical care system into a true health
      care system will require innovative strategies designed to merge the existing
      fragmented array of services into coordinated and comprehensive systems for
      delivering primary and preventive health care services in community settings. The
      Community-Oriented Primary Care concept successfully blends these functions and
      has achieved measurable results in reducing health care costs and improving
      access to preventive services for identified populations.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7567368
TI  - Nurse practitioners and physician assistants: do they have a role in your
      practice?
AB  - During the next decade, pediatricians will confront the difficult challenge of
      providing quality health care services to more children with more diverse and
      difficult problems, and they will have little or no additional funding to
      accomplish this task. Despite earlier predictions of surpluses in the pediatric
      work force, there are now shortages that will worsen if the current trend
      persists. Pediatric nurse practitioners (PNPs) and some physician assistants are
      being trained to perform health supervision care and to diagnose and treat the
      common illnesses of children. Substantial evidence suggests that PNPs provide
      quality health care services, and that collaborative teams of pediatricians and
      PNPs can provide high-quality, cost-effective care to a broader spectrum of
      children than can be served by either professional alone.

PMID- 7567370
TI  - Special needs of vulnerable and underserved populations: models, existing and
      proposed, to meet them.
AB  - The rapidly changing environment in the health care industry offers great
      challenges, especially to those providers who traditionally have cared for
      vulnerable and underserved populations. These populations have special health
      care needs resulting from various factors, including race, geography,
      environment, and lack of access. Some promising existing publicly funded models
      serve these populations well. Partnerships between these programs and private
      practitioners would be mutually beneficial to the practices and improve access to
      care.

PMID- 7567371
TI  - The integrated school health center: a new medical home.
AB  - During the past two decades, financial access to health care has improved for the
      very young, with emphasis on immunizations and medical care facilities for
      infants and mothers. Well-woman mandates, such as cancer detection and treatment
      programs, have improved the health of adult women. Even efforts to meet the needs
      of an ever-growing elderly population have improved. In contrast to expansions
      and improvements in care for the aforementioned populations, among others, there
      is still a population whose unmet medical needs have grown exponentially: school
      age youth. Morbidity and mortality for today's school-age children are linked
      most often to complex behavior patterns and psychosocial risk factors. Prevention
      and treatment of these patterns and factors often require a multidisciplinary
      approach using educational and case management strategies; social, mental health,
      dental, and nutritional services; and traditional medical services. In
      recognition of the school as the focus of many communities and in recognition of
      this population's disproportionate drain on medical expenditures, current and
      projected, there has been a push for more monies to be spent on developing
      integrated school-based and school-linked clinics. These clinics should focus on
      meeting community needs and should emphasize coordination and cooperation between
      private and public agencies. If such efforts are not continued into the 21st
      century, this least-served population, which on the surface seems to be the
      healthiest, will be a major factor in the rising cost of care, particularly
      because they lacked a medical home while they were school age.

PMID- 7567372
TI  - How to integrate your practice into the new health care system.
AB  - In the evolving health care delivery paradigm, physicians manage overall health
      status rather than illness, and providers rather than insurance companies bear
      the risk. Consequently, interest in prevention--long of prime interest to
      pediatricians--is increasing among all providers. The ethical practice of
      medicine in a managed care environment involves providing care at a level that
      avoids high cost with poor outcomes. High cost with poor outcomes can be the
      result of either undertreatment or overtreatment. Purchasers of health care today
      are clear about what they want--low cost, convenient access for their employees,
      medically appropriate, documented treatment, and patient satisfaction--and they
      are clear about how they intend to get what they want. Different areas of the
      country are at different stages in the evolution of managed care. Physicians who
      practice in markets that are still in early stages must plan ahead, taking the
      lead in shaping the changes that are occurring and preparing their practices for
      managed care. Otherwise, someone less concerned about quality of care will shape
      them. Solo or small group practices will survive, but those that survive will not
      be independent. The necessary affiliation with larger entities does not mean that
      clinical autonomy and freedom must be sacrificed.

PMID- 7567374
TI  - Nurses Practice Act, Prescriptive Authority Act become law.

PMID- 7567375
TI  - Simplified Employee Pension plans (SEPS): some questions and answers.

PMID- 7567376
TI  - A winning battle plan.

PMID- 7567373
TI  - The Louisiana Nurse Practice Act: what affects one, affects all.

PMID- 7567377
TI  - Elderly Protective Services in Louisiana.

PMID- 7567378
TI  - The doctrine of informed consent.

PMID- 7567379
TI  - Foot agility and toe gnosis/graphaesthesia as potential indicators of integrity
      of the medial cerebral surface: normative data and comparison with clinical
      populations.
AB  - A protocol was designed to identify quantitative indicators of the function of
      the medial surfaces of the cerebral hemispheres. Normative data were collected
      from 40 volunteers for foot agility, toe gnosis, and toe graphaesthesia. A total
      of 100 patients (most of whom had been referred for possible closed-head
      injuries) completed thorough neuropsychological and cognitive assessments.
      Deficits for toe graphaesthesia were most consistently correlated with general
      brain impairment and with scores for tasks whose normal performance requires the
      integrity of structures within the dorsal half of the medial cerebral
      hemispheres.

PMID- 7567380
TI  - Predicting preschool speech/language referral-status with the Lollipop Test and
      the Cognitive-Language Profile of the Early Screening Profiles.
AB  - 603 preschoolers who attended early childhood screenings were administered the
      Lollipop Test, the Cognitive Language Profile of the Early Screening Profiles,
      and the Fluharty Preschool Speech and Language Screening Test. Scores from the
      Lollipop and the Cognitive-Language Profile significantly predicted
      speech/language referral-status based on Fluharty scores and clinical judgment.

PMID- 7567381
TI  - Characteristics of motor performance, learning, warm-up decrement, and
      reminiscence during a balancing task.
AB  - Warm-up decrement and reminiscence effects have been primarily attributed to
      methods of distribution of practice. The present study investigated the effects
      of different amounts of practice on a balancing task and observed the differences
      in individual learning. Subjects were randomly assigned to a 5- or 10-trial
      practice group and performed a retention session on a stabilometer 1 wk. after
      the first set of trials. Subjects were given the same amount of rest between
      trials and sessions. Following the retention session subjects were assigned by
      retention performance into a warm-up decrement or reminiscence group for further
      comparison. The group with more practice had higher over-all performance. The
      warm-up decrement group showed more time-on-balance during the first practice
      session than the reminiscence group. The second session performance curves were
      nearly identical for the 5- and the 10-trial groups whether warm-up decrement or
      reminiscence occurred. These results suggested the importance of considering
      individual differences in retention of learning.

PMID- 7567382
TI  - Instantaneous change in sleep stage with noise of a passing truck.
AB  - The transient effects of passing truck noise on sleep polygraphs of 8 men were
      studied. The percentage of the sleep Stage 2 which changed from Stage 2 to Stage
      1, waking or movement time, was calculated. The shallowing of REM sleep was
      identified when it had changed to other stages, and the shallow epoch percentage
      was calculated for the REM sleep. The percentage of shallow epochs for Stage 2
      significantly increased against that of the control condition after exposure to
      noise but was not statistically significant for Stage REM. In conclusion, the
      shallowing or changes in the sleep Stage 2 or REM sleep with the passing truck
      noise might be observed at noise levels of less than 45 dBA or greater than 60
      dBA, respectively.

PMID- 7567383
TI  - Secular trends in suicide: the problem of generality and causation.

PMID- 7567384
TI  - Factors affecting accuracy of producing time intervals.
AB  - The present study assessed the accuracy of producing time intervals. 92 subjects
      were asked to produce three different time intervals (15, 30, and 60 sec.) under
      six experimental conditions during which they performed concurrent tasks of
      different cognitive difficulty and requiring different cognitive functions. Real
      life working situations guided the design of the experiment. Accuracy of time
      estimation was significantly affected by the length of the intervals to be
      produced and the concurrent tasks performed. 15-sec. intervals were more
      accurately estimated. Accuracy decreased as the cognitive demands of the
      concurrent tasks increased; subjects systematically overestimated the duration of
      the intervals. Having an activity requiring time estimation seems to have a
      positive effect on the accuracy of time estimation. The same was found for
      certain strategies aiding time estimation which were used spontaneously by
      certain subjects. No significant difference in the accuracy of estimation between
      women and men was found.

PMID- 7567386
TI  - Correlations of hopelessness with motivation and personality traits among
      Japanese school children.
AB  - Correlations for 628 children in Grades 2, 4, 5, and 6 of scores on hopelessness
      with measures of motivation for learning and personality traits were
      investigated. Hopelessness scores significantly correlated with lower scores on
      motivation. Also, hopelessness scores were significantly correlated with scores
      on personality traits of schizothymia, nervousness, and self-uncertainty.

PMID- 7567385
TI  - Cutaneous thresholds and anxiety: influence of eye orientation and lateral
      asymmetry.
AB  - This study investigated the combined influence of anxiety and eye orientation on
      cutaneous thresholds. The relationship between anxiety and the lateral
      differences was also examined. Right-handed subjects of low and high trait
      anxiety received weak electric shocks on either hand. Cutaneous thresholds were
      recorded when eyes were directed towards or away from the stimulated area. State
      anxiety was retrospectively assessed. As compared to a contralateral eye
      orientation, directing the eyes ipsilaterally to the stimulated area yielded
      lower thresholds for subjects low in trait anxiety. This effect was not observed
      for subjects high in trait anxiety. The benefit of the ipsilateral orientation
      was higher for subjects with lower state-anxiety scores as well. Besides,
      subjects low in trait anxiety presented a left-hand advantage which was not shown
      by those high in trait anxiety. The left-right difference in thresholds was also
      positively correlated with state anxiety. The eye-orientation results are
      discussed in terms of anxiety-induced modification of spatial attention and the
      differential hand sensitivity findings in terms of hemispheric specialization.

PMID- 7567387
TI  - Effect of tone on directional orientation during stepping in place with eyes
      closed.
AB  - To examine the effect of a tone on directional orientation during stepping in
      place with eyes closed 10 healthy adults ages 20 to 27 years stepped in place for
      120 seconds with eyes closed in 3 conditions: without a tone, with 1000-Hz pure
      tone, and with white noise. To examine how the subject rotated in stepping, both
      range and dispersion of the head's angular displacement were measured by a
      compass sensitive to terrestrial magnetism. Analysis showed that white noise was
      effective for directional orientation during stepping. Also, in the pure-tone
      condition, angular displacement of the head was similar to that in the no-tone
      condition. This result may have been due to the fact that the stationary wave
      created by the interference wave made sound normalization impossible.

PMID- 7567388
TI  - Alphanumeric sequencing and cognitive impairment among elderly persons.
AB  - Alphanumeric Sequencing involves the alternating recitation of counting and the
      alphabet. We report data on the use of this measure among 112 VA patients ranging
      in age from 61 to 100 years who were administered the Alphanumeric Sequencing,
      Trail Making Test, Digits Forward and Backward, the Mini-Mental State
      Examination, and the Behavioral Dyscontrol Scale. Persons who obtained scores <
      27 on the Mini-Mental State Examination or < 14 on the Behavioral Dyscontrol
      Scale performed significantly more poorly than those who scored higher. Both the
      time and errors were correlated (.11 to -.49) with measures of information
      processing and short-term memory.

PMID- 7567389
TI  - Gait disturbance of patients with vascular and Alzheimer-type dementias.
AB  - The gaits of 15 patients with senile dementia of the Alzheimer type and 15 with
      vascular dementia were compared with those of 15 healthy control subjects.
      Patients with senile dementia showed significantly slower velocity and shorter
      step length than the healthy controls, and those with vascular dementia exhibited
      a reduction on these two variables relative to patients with senile dementia of
      the Alzheimer type.

PMID- 7567390
TI  - Effects of auditory radio interference on a fine, continuous, open motor skill.
AB  - The effects of human speech on a fine, continuous, and open motor skill were
      examined. A tape of auditory human radio traffic was injected into a tank gunnery
      simulator during each training session for 4 wk. of training for 3 hr. a week.
      The dependent variables were identification time, fire time, kill time, systems
      errors, and acquisition errors. These were measured by the Unit Conduct Of Fire
      Trainer (UCOFT). The interference was interjected into the UCOFT Tank Table VIII
      gunnery test. A Solomon four-group design was used. A 2 x 2 analysis of variance
      was used to assess whether interference gunnery training resulted in improvements
      in interference posttest scores. During the first three weeks of training, the
      interference group committed 106% more systems errors and 75% more acquisition
      errors than the standard group. The interference training condition was
      associated with a significant improvement from pre- to posttest of 44% in over
      all UCOFT scores; however, when examined on the posttest the standard training
      did not improve performance significantly over the same period. It was concluded
      that auditory radio interference degrades performance of this fine, continuous,
      open motor skill, and interference training appears to abate the effects of this
      degradation.

PMID- 7567391
TI  - Estimating the true economic cost of suicide.

PMID- 7567392
TI  - An acoustic orientation system to promote independent indoor travel in blind
      persons with severe mental retardation.
AB  - An acoustic orientation system was devised to promote independent indoor travel
      in blind persons with mental retardation. The system was assessed with four blind
      adolescents, all affected by severe mental retardation. Data showed that the
      system was very useful in helping those adolescents orient and move independently
      in their daily environment and in a new (generalization) setting. The findings
      are discussed in relation to the characteristics of the system.

PMID- 7567393
TI  - Color-specificity to enhance identification of rear lights.
AB  - 30 male and 13 female licensed drivers were given a static reaction-time test for
      Donders Type B reactions to the onset of automotive rear lights. The lights were
      displayed as by conventional systems and by a new color-specific method referred
      to as the "Red Light Means Stop approach." When subjects were instructed to
      regard all red colored light as brake-signal light, both incidence of
      identification error and reaction time decreased. Results support the hypothesis
      that addition of color specificity to rear lighting might prevent some rear-end
      collisions which occur under adverse driving circumstances.

PMID- 7567395
TI  - Human EEG responses to classical music and simulated white noise: effects of a
      musical loudness component on consciousness.
AB  - The main purpose of the present study was to investigate the psychophysiological
      effects of music on human EEG. For this purpose, a sound modulator was developed
      which simulates the sound-pressure variations of a given piece of music by white
      noise (sim-music). Using this apparatus, the author tested the
      psychophysiological effects of music on human EEG. The electroencephalograms
      (EEG), electrocardiograms (ECG), and electrooculograms (EOG) of eight normal
      volunteers were recorded for a total of 21 min., 5 sec. per session for each
      subject under three sound conditions: silence for 5 min., two types of music
      (music) or two types of simulated noise (sim-music) for 11 min., 5 sec., followed
      by silence for another 5 min. Each subject was exposed to a total of 10 music and
      10 sim-music conditions. At the low consciousness level (drowsiness, Stage S1),
      higher delta component power densities were observed with sim-music than with
      music. Thus, even in the same Stage S1, entire physiological consciousness levels
      may be higher when listening to music than to sim-music. While listening to
      music, many subjects reported that they felt pleasantly relaxed or comfortable.
      However, with the sim-music, they reported feeling unpleasantly weary and sleepy.
      It seems that the mental set toward two sound conditions differed greatly for
      many subjects. In Stage S1, the differences in EEG slow components showed that
      the differences in consciousness had a physiological aspect and indicated
      differences in mental set toward both sound conditions and mental activity during
      the listening conditions.

PMID- 7567396
TI  - On the possibility of directly accessing every human brain by electromagnetic
      induction of fundamental algorithms.
AB  - Contemporary neuroscience suggests the existence of fundamental algorithms by
      which all sensory transduction is translated into an intrinsic, brain-specific
      code. Direct stimulation of these codes within the human temporal or limbic
      cortices by applied electromagnetic patterns may require energy levels which are
      within the range of both geomagnetic activity and contemporary communication
      networks. A process which is coupled to the narrow band of brain temperature
      could allow all normal human brains to be affected by a subharmonic whose
      frequency range at about 10 Hz would only vary by 0.1 Hz.

PMID- 7567394
TI  - Relationships among gender, cognitive style, academic major, and performance on
      the Piaget water-level task.
AB  - Many researchers have found that more college-age adults than would be expected
      fail Piaget's water-level task, with women failing more frequently than men. It
      has been hypothesized that differences in cognitive style may account for
      performance differences on the water-level task. In the present study, 27 male
      and 27 female architectural students and 27 male and 27 female liberal-arts
      students were assessed for their performance on both Piaget's Water-level Task
      and Witkin's Group Embedded Figures Test. No difference was found in performance
      of male and female architectural students on either task, but male liberal-arts
      students scored significantly higher than female liberal-arts students on both
      measures. A disembedding cognitive style predicted success on the water-level
      task for the architectural students but not for the liberal arts students.

PMID- 7567397
TI  - Cluster analysis of levels of body fatness in children.
AB  - The purpose of this study was to examine, using cluster analysis, the levels of
      body fatness as defined in the current national programs for children and youth
      fitness. A total of 1,056 examinees were drawn randomly from the published data
      of the National Children and Youth Fitness Study II, with 525 boys and 531 girls,
      ages 6 to 9 years. Their triceps and medial calf skinfold measures were used for
      the cluster analysis, including both the kth nearest-neighbor and the Ward's
      minimum variance procedures. Although multimodal clusters were found at four age
      groups according to the kth nearest-neighbor procedure, the Ward procedure and
      plotting of these clusters did not support their existence. It was concluded that
      the levels of body fatness reported in the current national children and youth
      fitness programs were arbitrarily defined.

PMID- 7567398
TI  - Redundant leading and following zeros in comparative numerical judgment.
AB  - The objective was to provide a more comprehensive understanding of how people
      make numerical comparative judgments when digits are contained in numbers with
      redundant leading or following zeros, e.g., 00080 and 800.000. These sequences of
      numbers often appear on computer display terminals (VDT) as line numbers, but
      surprisingly little research has been done on this. The experiment manipulated
      three aspects of numerical stimuli: (1) redundant leading zeros, (2) redundant
      following zeros, and (3) length of string of digits. The subjects were to push
      one of the two button-switches to respond whether two stimulus numbers shown on
      the computer screen were equal or unequal. The target stimuli contained several
      forms of redundant zeros, and each performance was assessed by response RT of the
      subjects. Analysis indicated five significant findings: (1) Redundant leading
      zeros hindered performance, (2) The effect of redundant following zeros depended
      on the stimulus type, (3) Over-all, longer digits took more processing time, (4)
      The RTs for the second-block trials were significantly faster than the first, and
      (5) Task performance was facilitated when the redundant zero representations were
      identical in both stimuli of a pair. Nonlexicographic processing seems to occur
      when feature identification can be used for numerical identification, that is,
      when the format is consistent. The research has implications for those in
      computer science to provide numerical formats which make comparative judgments as
      easy as possible.

PMID- 7567399
TI  - Suicide rates among Native Americans in 1890.

PMID- 7567400
TI  - Relations among heart rate, immediate memory, and time estimation under two
      different instructions.
AB  - The present study was done to elucidate the relations among heart rate, digit
      memory, and time estimation under two different instructions, standard and
      evaluative. 60 women heard and recalled 8 digits. Subjects reproduced 4-, 8-, and
      16-sec. durations of a buzzer and also estimated the durations. Data were
      discussed in terms of the hypothesis of an inverted U-shaped relationship between
      arousal and performance. These data suggest relations among the three variables
      which were influenced by two different instructions.

PMID- 7567402
TI  - Temporal coupling between external auditory information and the phases of
      walking.
AB  - The purpose of this study was to investigate the effects of an imposed external
      auditory constraint upon the temporal organization of walking. Ten subjects were
      videotaped walking normally (N) and with instructions to couple naturally, at mid
      swing, or at toe-off to a metronome beat. Based upon an analysis of variance and
      post hoc Scheffe tests most temporal variables were not significantly different
      among conditions. The duration of swing phase was significantly different between
      natural coupling and toe-off. The deviation from the metronome beat was
      significantly different between the natural coupling and both mid-swing and toe
      off. Subjects generally were not successful in achieving coupling during the
      latter conditions. Thigh and shank phase portraits were used to describe the
      system's organization to the external constraint.

PMID- 7567401
TI  - Gender differences in competitive stress.
AB  - Stress experienced in competitive basketball was investigated in a sample of 84
      men and 49 women recruited from players engaged in regular, organized,
      competitive grade basketball. Subjects were administered the Stressful Situations
      in Basketball Questionnaire which provides measures on 5 types of stress in
      competitive basketball. Analyses of gender differences showed that men reported
      more stress than female players on the "Team performance" scale. Research is
      required to evaluate whether this difference is due to a perception of women that
      they have less influence over the performance of the team or whether it is due to
      men having a higher stake in the results of competition.

PMID- 7567404
TI  - Imagery, concreteness, emotionality, meaningfulness, and pleasantness of words.
AB  - This account of the literature on the relationships among imagery, concreteness,
      emotionality, meaningfulness, and pleasantness shows high test-retest reliability
      for all five attributes which are stable for subjects of both genders and of
      several nationalities. Gender differences and the influence of attributes on
      other attributes are also examined.

PMID- 7567403
TI  - Suicide and parasuicide in Scotland.

PMID- 7567405
TI  - Preliminary predictions of athletic performance among collegiate baseball players
      with a biopsychosocial model.
AB  - This study investigated the association of nine biopsychosocial variables and
      athletic performance among 40 elite collegiate baseball players. High scores on
      confidence and perceived fitness and low scores on repressive denial, strength of
      religious faith, and sensitivity to glare were reliably associated with ratings
      of superior athletic performance by four coaches. Preliminary results suggest
      that the biopsychosocial model may prove useful in predicting athletic
      performance.

PMID- 7567406
TI  - Effects of exercise on dexterity.
AB  - As musicians occasionally report that their dextral facility is improved by
      recent exercise, it was hypothesized that manual dexterity would be influenced by
      a task requiring exertion. Before and after exertion on the Harvard Step Test,
      the experimental group's (n = 25) manual dexterity was tested on a grooved peg
      board. The control group's (n = 40) manual dexterity was measured before and
      after an inactive period. In both groups learning was significantly faster with
      the nondominant hand than with the dominant hand. Reasons why the hypothesis was
      not fully supported are discussed and suggestions for research noted.

PMID- 7567407
TI  - Personality correlates of correctly identifying genuine suicide notes.

PMID- 7567408
TI  - Birth order and communication skills of pharmacy students.
AB  - Pharmacy educators are training graduates in a concept of practice called
      pharmaceutical care. The movement towards patient care requires consideration of
      the personal and social qualities of trainees. All individuals attracted to
      pharmacy may not desire involvement in patient care. This preliminary study of
      pharmacy students of the relationships among birth order, empathy, and
      assertiveness behaviors using the Interpersonal Communication Inventory showed
      the incidence of firstborn students in this sample was not significantly higher
      than in the general population but the incidence of those born second was
      significantly lower. Regression analysis of individual items gave significant
      correlations between birth order and three items on the inventory. While few
      conclusions can be drawn, a clear direction for further research is indicated.

PMID- 7567409
TI  - Inaccurate feedback and performance on the Muller-Lyer illusion.
AB  - The effects of accurate and erroneous feedback on magnitude of illusion for the
      Muller-Lyer illusion were examined. The provision of accurate feedback
      substantially reduced the magnitude of the Muller-Lyer illusion whereas the
      influences of inaccurate feedback were dependent upon whether subjects were
      prompted to overestimate or to underestimate the length of the comparison line.

PMID- 7567410
TI  - Perceived vulnerability and control of martial arts and physical fitness
      students.
AB  - Anecdotal reports and limited research suggest that enrolling in self-defense
      courses can enhance feelings of control and reduce feelings of vulnerability;
      however, much self-defense is taught in the context of martial arts courses. To
      assess the effects of martial arts courses on perceptions of vulnerability and
      control, 83 students in physical fitness and 59 students in martial arts courses
      at 10 randomly chosen large universities responded to questionnaires. Martial
      arts students scored lower on control, higher on vulnerability, and higher on
      perceived likelihood of being injured than fitness students while enrolled in
      their courses. A year later, regardless of whether they had continued training,
      they scored higher on control and lower on vulnerability. Neither gender nor
      prior history of assault was related to responses. Enrolling in martial arts
      courses may not enhance people's feelings of control, at least in the initial
      stages of training.

PMID- 7567411
TI  - Antecedents of multidimensional competitive state anxiety and self-confidence in
      duathletes.
AB  - The purpose of this study was to explore the situational antecedents of
      multidimensional state anxiety among competitors in the sport of duathlon
      (run/cycle/run). Subjects (N = 122; Age: M = 28.3 yr., SD = 7.8 yr.) completed
      the Competitive Sport Anxiety Inventory-2 1 hr. before competition. In addition,
      they completed a 21-item Prerace Questionnaire modified for duathlon on which
      scores were factor analysed. Six factors accounted for 73.5% of the variance,
      similar to those identified by Jones, et al. in 1990. Step-wise multiple
      regression indicated that race goals and perceived readiness were significant
      predictors of cognitive anxiety, somatic anxiety, and self-confidence. Self
      confidence was also predicted by attitude toward previous performance. This
      finding supports the proposal that these anxiety subcomponents share common
      antecedents but challenges the notion that cognitive and somatic anxiety also
      have unique antecedents.

PMID- 7567412
TI  - Sex differences in color preferences among an elderly sample.
AB  - The purpose of the study was to assess differences in color preferences between
      the sexes. A sample of 193 retirees were asked to report their favorite colors.
      The pattern of frequencies for preferred color differed as a function of sex.
      Blue was chosen as the most preferred color by both sexes. Women preferred black
      and purple more than men did. Moreover, the men preferred red over pink, whereas
      the women preferred red and pink equally. The rank order of color preferences for
      this elderly group were very similar to the findings of Silver, et al. who
      sampled young adults in 1988.

PMID- 7567413
TI  - Effects of instruction on a divided visual-field task of face processing.
AB  - The purpose of the present study was to document that instruction effects can
      occur on tasks typically yielding left visual-field advantages. In a lateralized
      face-recognition task, 40 right-handers (20 men, 20 women) had to memorize pairs
      of faces and to respond to a probe face displaying positive or negative emotion
      and presented for 100 msec. 3.8 degrees on the left or right of a fixation cross.
      Half of the subjects had been instructed to learn the faces through a verbal
      strategy and the other half through an imagery strategy. Analysis of reaction
      times yielded significant complex interactions involving gender, coding
      instruction, visual field, and emotion for both Yes and No responses. A global
      left visual-field advantage was obtained in the analyses of accuracy and
      sensitivity data, but no significant effects were recorded in the analysis of
      decision rule. Thus, the instruction effects on left visual-field advantages were
      obtained through complex interactions on reaction times only. Further replication
      of these data would provide a more secure basis for causal interpretations.

PMID- 7567414
TI  - Effects of age and level of work experience on occurrence of accidents.
AB  - Results of a research study on the effects of age and work experience and their
      interaction on the occurrence of accidents in an agro-food sector are described.
      Three different levels of experience and six age groups were examined. Age and
      work experience significantly affected frequency and seriousness of accidents. A
      study of these two factors jointly shows that considerably higher rates of
      frequency and seriousness are found for the youngest and oldest subjects with low
      work experience. These analyses enable us to put forward several hypotheses
      concerning the mechanisms in the occurrence of accidents.

PMID- 7567415
TI  - Prospective and retrospective time estimates as a function of clock duration.
AB  - 12 independent groups of 18 subjects each estimated the duration of one of six
      'empty' intervals (10, 18, 26, 34, 42, and 50 sec.). Subjects were told of the
      time task either prior to (prospective paradigm) or after (retrospective
      paradigm) the presentation of the interval. The results are consistent with
      Hicks' 1992 finding of an interaction between temporal paradigm and interval
      duration. Whereas the shorter intervals (< 42 sec.) were estimated accurately in
      both the retrospective and the prospective paradigms, the longer intervals were
      estimated rather accurately in the prospective paradigm and underestimated in the
      retrospective paradigm.

PMID- 7567416
TI  - Subway suicide rates and national suicide rates.

PMID- 7567417
TI  - Re-examination of evidence questions Christman's (1989) report of moderate
      experimental support for the visual spatial frequency hypothesis.
AB  - The visual spatial frequency hypothesis contends that perceptual characteristics
      of stimulus arrays can affect the magnitude and direction of hemispheric
      asymmetries in laterality experiments. In a 1989 literature review, Christman
      reported that 45 of 79 experimental comparisons yielded significant interactions
      for side of hemispheric advantage x perceptual characteristic which supported the
      visual spatial frequency hypothesis, a level of support he characterized as
      moderate. Re-examination of those 45 outcomes shows that in 20 of them either a
      significant interaction for side of hemispheric advantage x perceptual
      characteristic was not found or, if it was, the particulars do not agree fully
      with predictions of the visual spatial frequency hypothesis as presented by
      Christman in the 1989 paper. These findings suggest that experimental support for
      the visual spatial frequency hypothesis is weak, not moderate as characterized by
      Christman.

PMID- 7567419
TI  - Anhedonia, depression, and suicidal ideation.

PMID- 7567418
TI  - Electromyographic effects of fatigue and task repetition on the validity of
      estimates of strong and weak muscles in applied kinesiological muscle-testing
      procedures.
AB  - The study investigated the effects of fatigue and task repetition on the
      relationship between integrated electromyogram and force output during subjective
      clinical testing of upper extremity muscles. Muscles were studied under two
      conditions differing in the nature and duration of constant force production
      (SHORT-F) and (LONG-F). The findings included a significant relationship between
      force output and integrated EMG, a significant increase in efficiency of muscle
      activity with task repetition, and significant difference between
      Force/integrated EMG ratios for muscles labeled "Strong" and "Weak" in the LONG-F
      condition. This supports Smith's 1974 notion that practice results in increased
      muscular efficiency. With fatigue, integrated EMG activity increased strongly and
      functional (force) output of the muscle remained stable or decreased. Fatigue
      results in a less efficient muscle process. Muscles subjectively testing "Weak"
      or "Strong" yield effects significantly different from fatigue.

PMID- 7567420
TI  - Handedness trends across age groups in a Japanese sample of 2316.
AB  - Hand-preference data of 2316 Japanese were analyzed by age groups, sex, and
      familial sinistrality. Right-hand preference increased across age groups at least
      up to 30 years for men, while women showed relatively stable and stronger
      preference for right-hand use. Unlike some Western studies, no linear trends
      across age groups were found for both sexes. Declining cultural censorship
      against left-handedness would not be responsible for the trends, since there was
      no evidence indicating such a decline in Japan. Hypotheses of reduced longevity
      and life-long adaptation to the right-handed world are not satisfactory either,
      since both hypotheses assume a linear trend spanning the entire life span. Thus,
      it seems that a single-factor hypothesis which explains all the results by
      resorting to a single cause does not account for the complex results found in
      this and other studies.

PMID- 7567421
TI  - Conditioned taste aversions and latent inhibition in Egyptian spiny mice and Long
      Evans rats.
AB  - The acquisition and extinction of a conditioned taste aversion in Egyptian spiny
      mice and Long-Evans rats was compared during 20 posttest sessions using a cross
      over design and double-blind control procedures. Spiny mice preexposed to a
      sucrose CS demonstrated more latent inhibition and a faster rate of extinction
      than did Long-Evans rats preexposed to the same CS. Preference indices did not
      differ between control animals or as a function of gender. The present results
      are the first report of the effects of latent inhibition on learning taste
      aversion in Egyptian spiny mice.

PMID- 7567423
TI  - Can we be intelligent about consciousness?

PMID- 7567424
TI  - Processing speed in the motion-induction effect.
AB  - The motion-induction effect, where an illusory motion is perceived within a bar
      when it is shown next to a spot presented slightly earlier, was studied with
      respect to the idea that it is based on differential processing speeds between
      the two ends of the bar. First, by using just a bar with a luminance gradient,
      the existence of a motion illusion (gradient motion) within such a bar was
      demonstrated, presumably due to the different processing speeds of differential
      luminances. When such a bar was used in the motion-induction effect, it was shown
      to modulate, for short delays, the strength of the effect up or down, according
      to the direction of the gradient with respect to the position of the spot. When
      the same bar was used in the double-motion-induction effect (split priming), in
      which motion is usually away from the later spot, it totally determined the
      perceived direction of illusory motion, independently of gradient direction with
      respect to the later spot or the time between the two spots. These results
      demonstrate, on the one hand, that differential local processing speed is a
      likely mechanism to underlie the motion-induction effect. On the other hand, they
      also suggest the involvement of other more global (and perhaps top-down)
      processes.

PMID- 7567422
TI  - Enhancement of randomness by flotation rest (restricted environmental stimulation
      technique).
AB  - This study was conducted to evaluate the positive effect of flotation REST on the
      production of random sequences, employing both behavioral and physiological
      measures. The subjects were 7 student volunteers who spent a 40-min. session
      lying alone on a bed in an isolation box and two 40-min. sessions floating in a
      commercially produced tank. Polygraph recordings (EEG, EOG, ECG and respiration)
      were made continuously. Randomness of orally generated sequences was measured by
      RIP scores based on the Polya-Eggenberger distribution in three test sessions,
      e.g., pre-, during, and post-REST period. Randomness increased in the floating
      condition, while those parameters decreased in the bed condition. Sleep-stage
      analysis and EEG spectral analysis showed that the flotation REST induced a more
      hypnagogic state and light sleep than did in-bed REST. It is speculated that the
      hypnagogic state and light sleep induced by floating enhanced random generation.

PMID- 7567426
TI  - The global figural characteristics in the Zollner illusion.
AB  - The Zollner illusion has been accounted for in terms of local interactions
      between the vertical lines and the crossing segments. Recently, however, some
      evidence supporting the importance of global figural characteristics--ie of
      figural elements that are not directly interacting with the test lines--in the
      occurrence of orientation illusions has been reported. Three experiments have
      been conducted with parts of the Zollner figure to test whether this illusion is
      affected by the global figural characteristics. The results indicate that,
      similarly to what has been observed for other orientation illusions, the Zollner
      illusion depends on both local and global characteristics of the stimulus
      configuration. In addition, results suggest a similar weight for both these
      figural characteristics in determining the occurrence of the illusory effect.
      Finally, relations among different orientation illusions are also discussed.

PMID- 7567425
TI  - Parallel independent encoding of orientation, spatial frequency, and contrast.
AB  - Subjects were presented with a set of 216 test gratings in random order. Each had
      a different combination of orientation, spatial frequency, and contrast. For each
      test grating, subjects were instructed to judge whether or not orientation was
      clockwise of the mean of the stimulus set, whether or not spatial frequency was
      higher than the mean of the stimulus set, and whether or not contrast was higher
      than the mean of the stimulus set. Each of the three sets of button presses was
      analyzed with respect to each of the three parameters, giving nine psychometric
      functions from one response set. It is concluded that, for gratings of high
      visibility, changes of orientation, spatial frequency, and contrast are encoded
      independently and in parallel, at least for small changes in these three visual
      parameters. In another experiment only one of the three parameters was varied at
      a time. Neither orientation-discrimination threshold, nor spatial-frequency
      discrimination threshold, nor contrast-discrimination threshold was appreciably,
      if at all, lower than when all three parameters were varied simultaneously. It is
      concluded that interactions between the processing of small changes in
      orientation, spatial frequency, and contrast are negligible when all three are
      processed simultaneously. It is proposed that trial-to-trial variations of
      orientation, spatial frequency, and contrast are unconfounded by opponent
      processing within a population of neurons, each of which confounds the three
      variables.

PMID- 7567428
TI  - Temporal-signal detection and individual differences in timing.
AB  - Signal-detection procedures were used in three experiments to examine sensitivity
      and bias in time judgments and to evaluate individual differences in timing. The
      task required subjects to judge whether visual stimuli were presented for a
      certain target duration (the 'signal') or for a slightly longer duration. In
      experiment 1, subjects performed versions of the task involving both short (2 s)
      and long (12 s) target stimuli. Analyses of sensitivity and bias measures (d' and
      beta) provided evidence for consistency in timing performance within individuals.
      In experiment 2, subjects were tested on a detection task with 5, 10, or 15 s
      targets, followed by a temporal-reproduction task involving stimulus durations
      ranging from 3 to 17 s. Subjects with high temporal sensitivity showed less error
      in their reproductions than subjects with low temporal sensitivity. In experiment
      3, subjects were pretested on a detection task with a 12 s target and then
      performed a temporal-production task where they attempted to generate a series of
      12 s intervals under either control or informational feedback conditions.
      Feedback improved accuracy and reduced variability in temporal productions.
      However, the low-temporal-sensitivity subjects were more variable in their
      responses under both conditions than were the high-sensitivity subjects. The
      results point to the utility of a temporal-signal-detection task both as a means
      for studying individual differences in timing and as a pretesting technique for
      assigning subjects to high-sensitivity and low-sensitivity groups to reduce error
      in time-judgment data.

PMID- 7567427
TI  - The orthogonal orientation shift and spatial filtering.
AB  - A line abutting two tilted flanks is apparently shifted towards the orientation
      orthogonal to the flanks and at the same time is reduced in its apparent length.
      It has been suggested that both effects are caused by band-pass spatial
      filtering, followed by location of the end points of the line at the peaks in the
      filtered image. Here implications of the filtering explanation of these effects
      are explored further. In the first experiment, it was predicted that orientation
      thresholds (as opposed to biases) would be increased for short line lengths, and
      would be further increased by abutting bars. The predictions were confirmed. It
      was shown in experiment 2 that the orientation shift was reduced by a small (4
      min arc) gap between target lines and orthogonal flanks. In experiment 3 the
      threshold elevations and the orientation shift produced by orthogonal and tilted
      flanks were compared. Last, in experiment 4, the threshold elevations and
      orientation shift produced by orthogonal and tilted flanks, at different retinal
      eccentricities varying from 0 to 3.2 deg were compared, and the prediction that
      the magnitude of the orientation shift would decrease with line length and
      increase with eccentricity was confirmed. The connection is explored between the
      orientation shift and the Zollner illusion, and demonstrations are presented of
      the Zollner effect in which target and inducing lines are of opposite contrast on
      a gray background. It is concluded that the Judd and Zollner illusions do not
      depend upon a single mechanism.

PMID- 7567429
TI  - More about the difference between men and women: evidence from linear neural
      networks and the principal-component approach.
AB  - The ability of a statistical/neural network to classify faces by sex by means of
      a pixel-based representation has not been fully investigated. Simulations with
      pixel-based codes have provided sex-classification results that are less
      impressive than those reported for measurement-based codes. In no case, however,
      have the reported pixel-based simulations been optimized for the task of
      classifying faces by sex. A series of simulations is described in which four
      network models were applied to the same pixel-based face code. These simulations
      involved either a radial basis function network or a perceptron as a classifier,
      preceded or not by a preprocessing step of eigendecomposition. It is shown that
      performance comparable to that of the measurement-based models can be achieved
      with pixel-based input (90%) when the data are preprocessed. The effect of the
      eigendecomposition preprocessing of the faces is then compared with spatial
      frequency analysis of face images and analyzed in terms of the perceptual
      information it captures. It is shown that such an examination may offer insight
      into the facial aspects important to the sex-classification process. Finally, the
      contribution of hair information to the performance of the model is evaluated. It
      is shown that, although the hair contributes to the sex-classification process,
      it is not the only important contributor.

PMID- 7567430
TI  - Judgment of gender through facial parts.
AB  - Japanese male and female undergraduate students judged the gender of a variety of
      facial images. These images were combinations of the following facial parts:
      eyebrows, eyes, nose, mouth, and the face outline (cheek and chin). These parts
      were extracted from averaged facial images of Japanese males and females aged 18
      and 19 years by means of the Facial Image Processing System. The results
      suggested that, in identifying gender, subjects performed identification on the
      basis of the eyebrows and the face outline, and both males and females were more
      likely to identify the faces as those of their own gender. The results are
      discussed in relation to previous studies, with particular attention paid to the
      matter of race differences.

PMID- 7567431
TI  - Auditory isochrony: time shrinking and temporal patterns.
AB  - It has previously been reported that the duration of short time intervals is
      conspicuously underestimated if they are preceded by shorter neighbouring time
      intervals. This illusion was called 'time shrinking' and it was argued that it
      strongly affects the perception of auditory rhythms. In the present study this
      supposition has been pursued in three experiments. In the first, temporal
      patterns consisting of two, three, and four intervals had to be judged for
      anisochrony, which was invoked by offsetting the last sound from its isochronous
      position. By a constant method, it was determined that the last sound of fast
      sequences (50 ms base interval) had to be delayed by about 30 ms in order for
      isochronous rhythms to be perceived. Another interesting finding was that for
      sound sequences with base intervals up to 200 ms it was the difference limen,
      rather than Weber's ratio, that was constant for anisochrony detection. In the
      second experiment, the temporal patterns comprised two intervals, presented
      serially or separately. The deviation of isochrony could be on either the first
      or the second interval. The data, gathered by an adaptive method, showed time
      shrinking to be effective even up to a base interval of 200 ms. The third
      experiment involved a constant method and anisochrony was implemented on the
      first interval of two interval patterns. Time shrinking affected perceived
      isochrony in sequences with base intervals of 50, 100, and 200 ms. It is argued
      that the paradoxical results of anisochrony detection can be explained in terms
      of time shrinking. Some anomalies of rhythm perception and production that are
      the result of time shrinking are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567432
TI  - I choose nursing because....

PMID- 7567433
TI  - Validation of electronic cell counts by quantitative buffy coat analysis (QBC).
AB  - A total of 458 eight blood cell counts, accompanied by blood film reviews of the
      same samples, were performed with an electronic cell counter and with the QBC. In
      the great majority of cases, the QBC gave fast and accurate control of the flags
      from the electronic counter, thus avoiding the necessity for manual validation
      with its associated risks of infection and contaminations. Furthermore, QBC non
      readability could be related to microcytosis and hypochromia and hence point to
      possible cases of congenital or acquired haemoglobinopathy.

PMID- 7567434
TI  - St14 (DXS52) VNTR in the Chinese population and its application to genetic
      diagnosis of haemophilia A.
AB  - The variable number of tandem repeats (VNTR) of St14 (DXS52) on the human X
      chromosome was analysed using the polymerase chain reaction (PCR) method.
      Screening of 78 X-chromosomes in 56 healthy Chinese individuals revealed the
      existence of at least seven different alleles in the the Chinese population, the
      corresponding amplified fragments and frequencies being 700 bp (60.3%), 1220 bp
      (1.3%), 1300 bp (2.6%), 1390 bp (11.5%), 1570 bp (12.8%), 1630 bp (6.4%) and 1690
      bp (5.1%). Total theoretical heterozygous rate was 60%. Compared to Caucasians,
      this Chinese population showed a markedly higher occurrence of low molecular
      weight fragments and a relatively low occurrence of high molecular weight
      fragments. Study of this polymorphism in 14 suspected haemophilia A carriers
      revealed half of them to be heterozygous. Thus, St14 VNTR analysis by PCR should
      prove to be a useful tool in the genetic diagnosis of haemophilia A in China.

PMID- 7567436
TI  - De novo acute myeloid leukemia in patients with Crohn's disease.
AB  - Crohn's disease (CD) has been occasionally reported to be associated with
      myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). From October
      1991 to June 1993, four AML patients with a previous history of CD but no history
      of MDS were referred to our institution. Three presented AML with a monoblastic
      proliferation (one AML4 and two AML5). Cytogenetic analysis revealed a normal
      karyotype in two patients, an inv(16) in another and a del(11)(q24-25) in the
      fourth. Interestingly, the three patients with AML4/AML5 had not received high
      doses of immunosuppressive agents, prior CD therapy ranging from 1 to 4 months
      sulfasalazine with additional azathioprine in one case.

PMID- 7567437
TI  - Pheochromocytoma and secondary erythrocytosis: role of tumour erythropoietin
      secretion.
AB  - Certain neoplasias can induce unregulated erythropoietin (EPO) secretion which
      results in secondary erythrocytosis. Pheochromocytoma associated with
      erythrocytosis constitute a rare condition, where the secondary red cell
      abnormality is believed to be due to tumour EPO secretion. In one such case of
      pheochromocytoma related erythrocytosis, quantitative determination of serum EPO
      by enzyme immunoassay was combined with immunohistochemical examination of tumour
      tissue sections to locate the site of EPO secretion. EPO levels were initially
      high but decreased after tumour surgery, while immunolocalization showed EPO to
      be secreted by the neoplastic cells.

PMID- 7567435
TI  - Naftazone accelerates human saphenous vein endothelial cell proliferation in
      vitro.
AB  - Restoration of a haemocompatible surface after endothelial damage induced by
      treatments such as embolectomy, angioplasty, endarterectomy or irradiation or
      following vascular graft implantation is an important factor for the ultimate
      success of these interventions. The development of substances which enhance
      endothelial cell growth and accelerate their proliferation is therefore of great
      interest in such situations. In the present work naftazone was shown to
      accelerate human saphenous vein endothelial cell proliferation in vitro at
      concentrations which did not alter the hemostatic balance, resulting in a cell
      density at confluence 20% higher than in controls. This compound was able to
      partially substitute for serum requirements and further displayed additive
      effects in the presence of fibroblast growth factors. Thus naftazone, an original
      synthetic molecule distinct from growth factor peptides, is a promising candidate
      drug for the amelioration of vascular repair.

PMID- 7567438
TI  - Cerebral venous sinus thrombosis associated with refractory anaemia with excess
      of blasts.
AB  - The present report describes a case of cerebral venous thrombosis occurring in a
      patient suffering from refractory anaemia with excess of blasts (RAEB). This
      unusual complication suggests that RAEB could be considered a potential
      prothrombotic state.

PMID- 7567441
TI  - [A new indication for Sandimmum (cyclosporine A). Press release from Sandoz
      Laboratories].

PMID- 7567439
TI  - Longitudinal melanonychia induced by hydroxyurea: four case reports and review of
      the literature.
AB  - Although the occurrence of skin lesions during long-term hydroxyurea therapy is
      well known, longitudinal melanonychia (LM) are more rarely described. In the
      present paper, we report four cases of LM associated with skin lesions induced by
      long-term daily hydroxyurea therapy (4 to 10 years), characterized by two
      uncommon aspects: late onset (2.5 to 5 years) and predominance of toenail
      involvement in three cases.

PMID- 7567440
TI  - [Account of the Roussel-Diamant symposium].

PMID- 7567442
TI  - In vivo interaction of the Escherichia coli integration host factor with its
      specific binding sites.
AB  - The histone-like protein integration host factor (IHF) of Escherichia coli binds
      to specific binding sites on the chromosome or on mobile genetic elements, and is
      involved in many cellular processes. We have analyzed the interaction of IHF with
      five different binding sites in vitro and in vivo using UV laser footprinting, a
      technique that probes the immediate environment and conformation of a segment of
      DNA. Using this generally applicable technique we can directly compare the
      binding modes and interaction strengths of a DNA binding protein in its
      physiological environment within the cell to measurements performed in vitro. We
      conclude that the interactions between IHF and its specific binding sites are
      identical in vitro and in vivo. The footprinting signal is consistent with the
      model of IHF-binding to DNA proposed by Yang and Nash (1989). The occupancy of
      binding sites varies with the concentration of IHF in the cell and allows to
      estimate the concentration of free IHF protein in the cell.

PMID- 7567443
TI  - Overexpression of DEAD box protein pMSS116 promotes ATP-dependent splicing of a
      yeast group II intron in vitro.
AB  - The group II intron bl1, the first intron of the mitochondrial cytochrome b gene
      in yeast is self-splicing in vitro. Genetic evidence suggests that trans-acting
      factors are required for in vivo splicing of this intron. In accordance with
      these findings, we present in vitro data showing that splicing of bl1 under
      physiological conditions depends upon the presence of proteins of a mitochondrial
      lysate. ATP is an essential component in this reaction. Overexpression of the
      nuclear-encoded DEAD box protein pMSS116 results in a marked increase in the ATP
      dependent splicing activity of the extract, suggesting that pMSS116 may play an
      important role in splicing of bl1.

PMID- 7567444
TI  - The Sry-related HMG box-containing gene Sox6 is expressed in the adult testis and
      developing nervous system of the mouse.
AB  - We have cloned and sequenced a full-length cDNA for the HMG box-containing, SRY
      related gene Sox6 from mouse. The deduced protein sequence of Sox6 has
      considerable homology with that of the previously determined Sox5 sequence. It
      seems likely that these genes have diverged more recently than other members of
      the SOX gene family, although the two genes map to different chromosomes in the
      mouse. In common with Sox5, Sox6 is highly expressed in the adult mouse testis
      and the HMG domains of both proteins bind to the sequence 5'-AACAAT-3'. This
      suggests that the two genes may have overlapping functions in the regulation of
      gene expression during spermatogenesis in the adult mouse. However, Sox6 may have
      an additional role in the mouse embryo, where it is specifically expressed in the
      developing nervous system.

PMID- 7567445
TI  - Variable pause positions of RNA polymerase II lie proximal to the c-myc promoter
      irrespective of transcriptional activity.
AB  - Transcriptional activation of the c-myc proto-oncogene is mediated by the
      transition of promoter proximal, paused RNA polymerase II (pol II) into a
      processive transcription mode. Using a transcription assay which allows the high
      resolution mapping of transcriptional complexes in intact nuclei, we have
      characterized the promoter proximal pause positions of pol II. Pol II paused in a
      nucleosome-free region close to the transcription start site as well as further
      downstream, between positions +17 and +52. These pause positions were detected in
      both transcriptionally active and inactive c-myc genes. Pharmacological
      inhibition of the C-terminal phosphorylation of the large subunit of pol II did
      not affect the paused transcription complexes, but had an inhibitory effect on
      transcription of nucleosomal DNA downstream of position +150. The different
      properties of pol II proximal and distal to the promoter suggest a model in which
      c-myc transcription is regulated by the activation of promoter bound polymerases.

PMID- 7567446
TI  - C to U editing and modifications during the maturation of the mitochondrial
      tRNA(Asp) in marsupials.
AB  - In marsupial mitochondria, the nucleotide residue at the second position of the
      anticodon of the tRNA for aspartic acid is changed post-transcriptionally such
      that the translational machinery recognizes it as a uracil rather than the
      cytosine residue encoded in the gene. By postlabeling nucleotide analysis, we
      show here that the cytosine residue is converted to a conventional uracil residue
      in an RNA editing event that affects approximately half of the tRNA molecules
      under steady state conditions. Furthermore, we have identified three different
      tRNA(Asp) species which all carry three pseudouridines and two methylations but
      have the anticodons GCC, GUC and QUC respectively, the latter representing a rare
      example of queuine incorporation into a mitochondrial tRNA. This allows us to
      describe a likely sequential order of modification of the tRNA(Asp), where
      methylations and conversions of uridines to pseudouridines precede the editing
      event, while the exchange of guanine by queuine takes place after the C to U
      editing event.

PMID- 7567447
TI  - DNA sequence preferences of several AT-selective minor groove binding ligands.
AB  - We have examined the interaction of distamycin, netropsin, Hoechst 33258 and
      berenil, which are AT-selective minor groove-binding ligands, with synthetic DNA
      fragments containing different arrangements of AT base pairs by DNase I
      footprinting. For fragments which contain multiple blocks of (A/T)4 quantitative
      DNase I footprinting reveals that AATT and AAAA are much better binding sites
      than TTAA and TATA. Hoechst 33258 shows that greatest discrimination between
      these sites with a 50-fold difference in affinity between AATT and TATA. Alone
      amongst these ligands, Hoechst 33258 binds to AATT better than AAAA. These
      differences in binding to the various AT-tracts are interpreted in terms of
      variations in DNA minor groove width and suggest that TpA steps within an AT
      tract decrease the affinity of these ligands. The behaviour of each site also
      depends on the flanking sequences; adjacent pyrimidine-purine steps cause a
      decrease in affinity. The precise ranking order for the various binding sites is
      not the same for each ligand.

PMID- 7567448
TI  - Conformational changes induced by DNA binding of NF-kappa B.
AB  - The transcription factor NF-kappa B makes extensive contacts with its recognition
      site over one complete turn of the double helix. Structural transitions, in both
      protein and DNA, that accompany formation of the DNA-protein complex were
      analysed by proteinase sensitivity and circular dichroism (CD) spectroscopy. In
      the absence of DNA chymotrypsin cleaved p50 after residues Y60 and N78, while
      proteinase K cleaved p50 after residues S74 and Q180. Previous experiments had
      indicated that trypsin cleaved p50 after K77. Cleavages after Y60, S74, K77 and
      N78 were blocked in the presence of bound DNA, whereas cleavage after Q180 was
      enhanced. Y60, S74, K77 and N78 are all located in the p50 N-terminal domain AB
      loop, whereas Q180 is located in the mainly alpha-helical region between p50 N
      terminal domain beta-strands G' and H. As only Y60 makes direct contact with the
      DNA it is likely that the AB loop is highly unstructured in the absence of DNA,
      but is held in a rigid, proteinase-resistant structure by bound DNA. These
      conclusions were supported by CD spectroscopic studies of recombinant p50 and p65
      homodimers, which indicated that both species changed conformation when binding
      DNA. Examination of the near UV CD spectra revealed that with some DNA sequences
      the bound and free forms of the DNA assumed different conformations. While this
      was evident for a fully symmetrical, high affinity recognition site DNA, it was
      not apparent with less tightly bound DNA.

PMID- 7567450
TI  - Rational design of point mutation-selective antisense DNA targeted to codon 12 of
      Ha-ras mRNA in human cells.
AB  - Antisense oligodeoxynucleotides targeted to Ha-ras mRNA have been designed to
      discriminate between the codon 12-mutated oncogene and the normal proto-oncogene.
      An in vitro assay using two different sources of RNase H (rabbit reticulocyte
      lysates and nuclear extract from HeLa cells) was used to characterize
      oligonucleotide binding to normal and mutated Ha-ras mRNA. Short oligonucleotides
      (12- or 13mers) centered on the mutation had a very high discriminatory
      efficiency. Longer oligonucleotides (16mers) did not discriminate efficiently
      between the mutated and the normal mRNA. We have tested the efficacy of
      dodecanucleotides to induce RNase H cleavage of the full-length mRNA, moving the
      target sequence from the loop to the stem region which is formed in the vicinity
      of mutated codon 12. The most selective oligonucleotides were centered on the
      mutation which is located near the junction between the loop and stem regions
      even though they were less efficient at inducing RNase H cleavage than those
      targeted to the loop region. The 12mer antisense oligonucleotide with the highest
      discriminatory power was selected for cell culture studies. This oligonucleotide
      inhibited the proliferation of a human cell line which had been transformed with
      the mutated Ha-ras gene (HBL100ras1) but had no effect on the parental cell line
      which was transfected with the vector DNA (HBL 100neo) and expressed only the
      normal Ha-ras gene. Growth inhibition of HBL100ras1 cells was associated with
      specific ablation of targeted Ha-ras mRNA as shown by RT-PCR. These results show
      that 'in vitro' evaluation using an RNase H assay allowed us to select an
      antisense oligonucleotide which elicited a selectivity towards point-mutated Ha
      ras mRNA when added at 10 microM concentration to the culture medium of cells
      expressing wild type and mutated Ha-ras mRNA.

PMID- 7567449
TI  - A novel DNA-binding domain that may form a single zinc finger motif.
AB  - MNB1a is a DNA-binding protein from maize that interacts with the 35S promoter of
      cauliflower mosaic virus. This protein did not show significant homologies with
      any other DNA-binding protein and MNB1a seemed to be a member of a multigene
      family. In this study, isolation of cDNAs from the gene family to which MNB1a
      belongs revealed a unique conserved domain, referred to herein as the Dof domain,
      that contains a novel cysteine-rich motif for a single putative zinc finger. The
      amino acid sequence of the Dof domain and the arrangement of cysteine residues in
      this domain differ from those of known zinc finger motifs. However, the Dof
      domain was shown to be a DNA-binding domain that required Zn2+ ions for activity.
      Mutations at cysteine residues eliminated the DNA-binding activity of MNB1a.
      Thus, the Dof domain may be classified as a novel zinc finger motif. In addition,
      Southern blot analysis and a survey of DNA databases suggested that proteins that
      include Dof domains might exist in other eukaryotes, at least in the plant
      kingdom.

PMID- 7567452
TI  - On the role of rRNA tertiary structure in recognition of ribosomal protein L11
      and thiostrepton.
AB  - Ribosomal protein L11 and an antibiotic, thiostrepton, bind to the same highly
      conserved region of large subunit ribosomal RNA and stabilize a set of NH4(+)
      dependent tertiary interactions within the domain. In vitro selection from
      partially randomized pools of RNA sequences has been used to ask what aspects of
      RNA structure are recognized by the ligands. L11-selected RNAs showed little
      sequence variation over the entire 70 nucleotide randomized region, while
      thiostrepton required a slightly smaller 58 nucleotide domain. All the selected
      mutations preserved or stabilized the known secondary and tertiary structure of
      the RNA. L11-selected RNAs from a pool mutagenized only around a junction
      structure yielded a very different consensus sequence, in which the RNA tertiary
      structure was substantially destabilized and L11 binding was no longer dependent
      on NH4+. We propose that L11 can bind the RNA in two different 'modes', depending
      on the presence or absence of the NH4(+)-dependent tertiary structure, while
      thiostrepton can only recognize the RNA tertiary structure. The different RNA
      recognition mechanisms for the two ligands may be relevant to their different
      effects on protein synthesis.

PMID- 7567451
TI  - A T to G mutation in the polypyrimidine tract of the second intron of the human
      beta-globin gene reduces in vitro splicing efficiency: evidence for an increased
      hnRNP C interaction.
AB  - In a patient with a beta-thalassemia intermedia, a mutation was identified in the
      second intron of the human beta-globin gene. The U-->G mutation is located within
      the polypyrimidine tract at position -8 upstream of the 3' splice site. In vivo,
      this mutation leads to decreased levels of the hemoglobin protein. Because of the
      location of the mutation and the role of the polypyrimidine tract in the splicing
      process, we performed in vitro splicing assays on the pre-messenger RNA (pre
      mRNA). We found that the splicing efficiency of the mutant pre-mRNA is reduced
      compared to the wild type and that no cryptic splice sites are activated.
      Analysis of splicing complex formation shows that the U-->G mutation affects
      predominantly the progression of the H complex towards the pre-spliceosome
      complex. By cross-linking and immunoprecipitation assays, we show that the hnRNP
      C protein interacts more efficiently with the mutant precursor than with the wild
      type. This stronger interaction could play a role, directly or indirectly, in the
      decreased splicing efficiency.

PMID- 7567453
TI  - RNase H is responsible for the non-specific inhibition of in vitro translation by
      2'-O-alkyl chimeric oligonucleotides: high affinity or selectivity, a dilemma to
      design antisense oligomers.
AB  - Ribonuclease H (RNase H) which recognizes and cleaves the RNA strand of
      mismatched RNA-DNA heteroduplexes can induce non-specific effects of antisense
      oligonucleotides. In a previous paper [Larrouy et al. (1992), Gene, 121, 189
      194], we demonstrated that ODN1, a phosphodiester 15mer targeted to the AUG
      initiation region of alpha-globin mRNA, inhibited non-specifically beta-globin
      synthesis in wheat germ extract due to RNase H-mediated cleavage of beta-globin
      mRNA. Specificity was restored by using MP-ODN2, a methylphosphonate
      phosphodiester sandwich analogue of ODN1, which limited RNase H activity on non
      perfect hybrids. We report here that 2'-O-alkyl RNA-phosphodiester DNA sandwich
      analogues of ODN1, with the same phosphodiester window as MP-ODN2, are non
      specific inhibitors of globin synthesis in wheat germ extract, whatever the
      substituent (methyl, allyl or butyl) on the 2'-OH. These sandwich oligomers
      induced the cleavage of non-target beta-globin RNA sites, similarly to the
      unmodified parent oligomer ODN1. This is likely due to the increased affinity of
      2'-O-alkyl-ODN2 chimeric oligomers for both fully and partly complementary RNA,
      compared to MP-ODN2. In contrast, the fully modified 2'-O-methyl analogue of ODN1
      was a very effective and highly specific antisense sequence. This was ascribed to
      its inability (i) to induce RNA cleavage by RNase H and (ii) to physically
      prevent the elongation of the polypeptide chain.

PMID- 7567455
TI  - A DNA binding factor (UBF) interacts with a positive regulatory element in the
      promoters of genes expressed during meiosis and vegetative growth in yeast.
AB  - We have studied the bipartite regulatory element UASH/URS1 in the promoter of
      HOP1, whose product is required for synapsis and correct pairing of homologous
      chromosomes during the first meiotic division. HOP1 is transcriptionally
      repressed by the URS1 motif during vegetative growth and induced during meiotic
      prophase by the UASH motif in cooperation with the bifunctional URS1 site, which
      is required for full induction of HOP1. While URS1 is bound in vitro by the Buf
      and Ume6 repressor proteins, we demonstrate for the first time by electrophoretic
      mobility shift assays and interference footprinting that the UASH site interacts
      in vitro with a novel factor called UBF (UASH binding factor) which is present in
      haploid and diploid cycling, as well as sporulating cells. Point mutations in the
      HOP1 UASH motif abolish UBF-dependent DNA binding activity in vitro and meiotic
      HOP1 gene expression in vivo. Furthermore, we show that UBF binds in vitro to
      UASH-like sequences in the promoter regions of several meiosis-specific and non
      specific genes and propose that UBF mediates gene expression through its
      interaction with the UASH motif in both cycling and sporulating cells.

PMID- 7567454
TI  - Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins.
AB  - Somatic sex determination in Drosophila depends on the expression of Sex-lethal
      (Sxl), whose level is determined by the relative number of X chromosomes and sets
      of autosomes (X:A ratio). The first step in regulation of Sxl expression is
      transcriptional control from its early promoter and several genes encoding
      transcription factors of the helix-loop-helix (HLH) family such as daughterless
      (da), sisterless-b (sis-b), deadpan (dpn) and extramacrochaetae (emc) have been
      implicated. By the use of transfection assays and in vitro binding experiments,
      here we show that da/sis-b heterodimers bind several sites on the Sxl early
      promoter with different affinities and consequently tune the level of active
      transcription from this promoter. Interestingly, our data indicate that
      repression by the dpn product of da/sis-b dependent activation results from
      specific binding of dpn protein to a unique site within the promoter. This
      contrasts with the mode of emc repression, which inhibits the formation of the
      da/sis-b heterodimers. These results reveal the molecular mechanisms by which Sxl
      gene transcription is positively or negatively regulated to control somatic sex
      determination.

PMID- 7567457
TI  - 6-Oxocytidine a novel protonated C-base analogue for stable triple helix
      formation.
AB  - 2'-O-Methyl-3'-O-phosphoramidite building blocks of 6-oxocytidine 6 and its 5
      methyl derivative 7, respectively, were synthesized and incorporated via
      phosphoramidite chemistry in 15 mer oligodeoxynucleotides [d(T72T7), S2;
      d(T73T7), S3] to obtain potential Py.Pu.Py triplex forming homopyrimidine
      strands. UV thermal denaturation studies and CD spectroscopy of 1:1 mixtures of
      these oligomers and a 21 mer target duplex [d(C3A7GA7C3)-d(G3T7CT7G3), D1] with a
      complementary purine tract showed a nearly pH-independent (6.0-8.0) triple helix
      formation with melting temperatures of 21-19 degrees C and 18.5-17.5 degrees C,
      respectively (buffer system: 50 mM sodium cacodylate, 100 mM NaCl, 20 mM MgCl2).
      In contrast, with the corresponding 15mer deoxy-C-containing oligonucleotide
      [d(T(7)1T7), S1] triplex formation was observed only below pH 6.6. Specificity
      for the recognition of Watson-Crick GC-base pairs was observed by pairing the
      modified C-bases of the 15mers with all other possible Watson-Crick-base
      compositions in the target duplex [d(C3A7XA7C3)-d(G3T7YT7G3), X = A,C,T; Y =
      T,G,A, D2-4]. Additionally, the Watson-Crick-pairing of the modified oligomers S2
      and S3 was studied.

PMID- 7567456
TI  - Repair of plasmid and genomic DNA in a rad7 delta mutant of yeast.
AB  - Repair of UV-induced cyclobutane pyrimidine dimers (CPDs) was examined in a yeast
      plasmid of known chromatin structure and in genomic DNA in a radiation-sensitive
      deletion mutant of yeast, rad7 delta, and its isogenic wild-type strain. A whole
      plasmid repair assay revealed that only approximately 50% of the CPDs in plasmid
      DNA are repaired after 6 h in this mutant, compared with almost 90% repaired in
      wild-type. Using a site-specific repair assay on 44 individual CPD sites within
      the plasmid we found that repair in the rad7 delta mutant occurred primarily in
      the transcribed regions of each strand of the plasmid, however, the rate of
      repair at nearly all sites measured was less than in the wild-type. There was no
      apparent correlation between repair rate and nucleosome position. In addition,
      approximately 55% of the CPDs in genomic DNA of the mutant are repaired during
      the 6 h period, compared with > 80% in the wild-type.

PMID- 7567459
TI  - Deformed expression in the Drosophila central nervous system is controlled by an
      autoactivated intronic enhancer.
AB  - Deformed (Dfd) is a Drosophila homeotic selector gene required for normal
      development of maxillary segment morphology in the larval and adult head.
      Consistent with this function, Dfd transcripts are restricted to epidermal,
      mesodermal and neural cells in the embryonic mandibular and maxillary primordia.
      Previous studies have identified a far upstream element in Dfd sequences which
      functions as an epidermal-specific autoregulatory enhancer. In a search through
      35 kb of Dfd sequences for additional transcriptional control elements, we have
      identified a 3.2 kb DNA fragment containing an enhancer that mimics the
      expression of Dfd in the subesophageal ganglion of the embryonic central nervous
      system. This Neural autoregulatory enhancer (NAE) maps in the large Dfd intron
      just upstream of the homeobox exon and requires Dfd protein function for its full
      activity. A 608 bp NAE subfragment retains regulatory function that is
      principally localized in the subesophageal ganglion. This small region of the
      Drosophila melanogaster genome contains numerous blocks of sequence conservation
      with a comparable region from the Dfd locus of D.hydei. A pair of conserved
      blocks of NAE sequence match a Dfd protein binding site in the epidermal
      autoregulatory element, while another conserved sequence motif is repeated
      multiple times within the 608 bp subelement.

PMID- 7567458
TI  - TBP binding and the rate of transcription initiation from the human beta-globin
      gene.
AB  - DNA-protein interaction studies in vitro revealed several factors binding over
      the TATA box and the region of transcription initiation (cap) site of the human
      beta-globin promoter; TATA binding protein TBP at -30, Sp1 at -19, GATA-1 at -12
      and +5, YY1 at -9 and a novel factor C1 over the site of initiation (-4 to +7).
      Point mutants which specifically abolish the binding of each of these proteins
      were tested in a beta-globin locus control region (LCR) construct which allows
      quantitative comparisons at physiological levels of transcription. Only mutants
      which drastically affect the binding of TBP resulted in decreased levels of
      transcription. A threshold value of TBP binding of 15-30% of wild type was
      sufficient to give normal levels of transcription. This indicates that the
      association of TF IID with the TATA box is not limiting in the rate of initiation
      of transcription.

PMID- 7567460
TI  - Genotypic analysis of multiple loci in somatic cells by whole genome
      amplification.
AB  - To screen multiple loci in small purified samples of diploid and aneuploid cells
      a PCR-based technique of whole genome amplification was adapted to the study of
      somatic lesions. DNA samples from different numbers of flow-sorted diploid and
      aneuploid cells from biopsies were amplified with a degenerate 15mer primer.
      Aliquots of these reactions were then used in locus-specific reactions using a
      single round of PCR cycles with individual sets of primers representing
      polymorphic markers for different regions. As a result, polymorphic markers for
      different chromosomal regions, including VNTRs and dinucleotide repeats, can be
      used to perform up to 30 locus-specific PCR assays with a single sample obtained
      from fewer than 1000 cells.

PMID- 7567461
TI  - HYS2, an essential gene required for DNA replication in Saccharomyces cerevisiae.
AB  - To investigate cell cycle regulation at the S or G2 phase in Saccharomyces
      cerevisiae, we have isolated mutants displaying supersensitivity to hydroxyurea
      (HU), a chemical that inhibits DNA replication. Such mutants, which we have named
      hydroxyurea sensitive (hys), defined four linkage groups and we characterized the
      hys2 mutation in this study. The hys2-1 mutant displays temperature sensitive
      growth and a constellation of phenotypes indicating defective DNA metabolism. At
      the restrictive temperature, hys2-1 cells arrest as large budded cells with a
      single nucleus at the neck of the bud and a short spindle. The hys2-1 mutant
      exhibits increased rates of chromosome loss and recombination. Additionally, hys2
      1 appears to accumulate incompletely replicated DNA that can be detected by a
      pulse field electrophoresis assay. Finally, deletion of RAD9 in a hys2-1 strain
      decreases the percentage of arrested cells, suggesting that an intact RAD9
      checkpoint is required for the cell cycle arrest in hys2-1 cells. HYS2 encodes a
      55 kDa protein that is essential for viability at all temperatures. Taken
      together, these data suggest that Hys2 plays a role in DNA replication.

PMID- 7567462
TI  - An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the
      chicken beta-tropomyosin pre-mRNA.
AB  - Computer analysis of human intron sequences have revealed a 50 nucleotide (nt) GC
      rich region downstream of the 5' splice site; the trinucleotide GGG occurs almost
      four times as frequently as it would in a random sequence. The 5' part of a beta
      tropomyosin intron exhibits six repetitions of the motif (A/U)GGG. In order to
      test whether these motifs play a role in the splicing process we have mutated
      some or all of them. Mutated RNAs show a lower in vitro splicing efficiency when
      compared with the wild-type, especially when all six motifs are mutated (> 70%
      inhibition). Assembly of the spliceosome complex B and, to a lesser extent, of
      the pre-spliceosome complex A also appears to be strongly affected by this
      mutation. A 55 kDa protein within HeLa cell nuclear extract is efficiently cross
      linked to the G-rich region. This protein is present in the splicing complexes
      and its cross-linking to the pre-mRNA requires the presence of one or several
      snRNP. Altogether our results suggest that the G-rich sequences present in the 5'
      part of introns may act as an enhancer of the splicing reaction at the level of
      spliceosome assembly.

PMID- 7567463
TI  - Nitrogen mustard inhibits transcription and translation in a cell free system.
AB  - Nitrogen mustard and its derivatives such as cyclophosphamide, chlorambucil and
      melphalan are widely used anti-cancer agents, despite their non-specific reaction
      mechanism. In this study, the effect of alkylation by nitrogen mustard of DNA and
      RNA (coding for a single protein) was investigated using both a translation
      system and a coupled transcription/translation system. When alkylated DNA was
      used as the template for coupled transcription and translation, a single
      translation product corresponding to the 62 kDa luciferase protein was
      synthesised. Production of the translated product encoded by this template was
      inhibited by mustard concentrations as low as 10 nM, and 50% inhibition occurred
      with 30 nM mustard. A primer extension assay employed to verify alkylation sites
      on the DNA revealed that all guanine residues on the DNA template are susceptible
      to alkylation by nitrogen mustard. Similarly, when alkylated RNA was used as the
      template for protein synthesis, the amount of the 62 kDa luciferase protein
      decreased with increasing mustard concentration and a range of truncated
      polypeptides was synthesised. Under these conditions 50% inhibition of
      translation occurred with approximately 300 nM mustard (i.e. approximately 10
      times that required for similar inhibition using an alkylated DNA template).
      Furthermore, a gel mobility shift assay revealed that mustard alkylation of the
      RNA template results in the formation of a more stable retarded RNA complex. The
      functional activity of the luciferase protein decreased with alkylation of both
      the DNA and RNA templates, with a half-life of loss of activity of 1.1 h for DNA
      exposed to 50 nM mustard, and 0.5 h for RNA exposed to 50 microM mustard. The
      data presented support the notion that DNA is a critical molecule in the mode of
      action of mustards.

PMID- 7567464
TI  - R-loop stability as a function of RNA structure and size.
AB  - The sequence-specific formation of R-loops can be assayed using RNAs which
      overlap a HindIII cleavage site in a 3.5 kb plasmid. Chemical modification of the
      displaced DNA strand has permitted stabilization of these R-loops and allowed a
      systematic investigation of the dependence of these triple-stranded structures on
      the chain length and structure of the input RNA. RNAs as short as 50 nt form
      stable R-loops if 5-allylamine uridines (Uaa-RNA) are used in place of normal
      uridines; normal RNAs must be 100 nt long to form R-loops quantitatively. Since
      acetic anhydride decreases the hybridization efficiency of Uaa-RNAs, the positive
      charge of the RNAs must diminish the electrostatic repulsion of the three
      negatively charged phosphodiester backbones. The dependence of R-loop stability
      on the length of RNA can be stimulated with a random walk model, which also
      applies to strand migration within Holiday junctions. R-loop hybridization
      provides a versatile method to generate single-stranded DNA in a sequence
      selective manner.

PMID- 7567465
TI  - Double stranded scission of DNA directed through sequence-specific R-loop
      formation.
AB  - R-loop formation with short (100 nt) RNAs provides a highly flexible and
      stringent method to achieve sequence-specific separation of target DNA at any
      given sequence. After stabilization of R-loops with glyoxal and removal of the
      RNA through RNase treatment the remaining single-stranded DNA bubble provides a
      highly favorable substrate for attenuated micrococcal nuclease. We investigated
      this method for sequence-specific scission of double-stranded DNA and achieved
      quantitative scission of 3-5 kb plasmids. The applicability to larger size DNA is
      demonstrated through specific excision of the intervening segment between two R
      loops from a P1 plasmid of approximately 120 kb.

PMID- 7567468
TI  - Convergent DNA synthesis: a non-enzymatic dimerization approach to circular
      oligodeoxynucleotides.
AB  - We report a novel convergent approach to the construction of circular DNA
      oligonucleotides from two smaller linear precursors. Circular DNAs 34-74
      nucleotides (nt) in size are constructed non-enzymatically in a single step from
      two half-length oligomers. A DNA template is used to assemble the constituent
      parts into a triple helical complex which brings the four reactive ends together
      for chemical ligation with BrCN/imidazole/Ni2+. A homodimerization reaction
      strategy is successfully used on a small scale to construct circles 42, 58 and 74
      nt in size. In addition, a heterodimerization strategy is successfully used in
      two cases to construct circular 34mers from different 16mer and 18mer precursors.
      Measurement of preparative yields for one biologically active 34mer circle shows
      that the dimerization strategy gives a yield higher than that from conventional
      cyclization and nearly as high as that for a normally synthesized linear DNA,
      establishing that there is not necessarily a yield penalty for circle
      construction. Six additional preparative circle constructions, giving conversions
      of approximately 33-85% from precursors to circular product, are also described.
      Convergent strategies allow the construction of medium and large size DNA
      molecules in higher yields than can be achieved by standard linear synthesis
      alone.

PMID- 7567466
TI  - A small modified hammerhead ribozyme and its conformational characteristics
      determined by mutagenesis and lattice calculation.
AB  - A prototypic hammerhead ribozyme has three helices that surround an asymmetrical
      central core loop. We have mutagenized a hammerhead type ribozyme. In agreement
      with previous studies, progressive removal of stem-loop II from a three stemmed
      ribozyme showed that this region is not absolutely critical for catalysis.
      However, complete elimination of stem II and its loop did reduce, but did not
      eliminate, function. In a stem-loop II-deleted ribozyme, activity was best
      preserved when a purine, preferably a G, was present at position 10.1. This G
      contributed to catalysis irregardless of its role as either one part of a
      canonical pair with a C residue at 11.1 or a lone nucleotide with C (11.1)
      deleted. Computational methods using lattices generated 87 million three
      dimensional chain forms for a stem-loop II-deleted RNA complex that preserved one
      potential G.C base pair at positions 10.1 and 11.1. This exhaustive set of chain
      forms included one major class of structures with G(10.1) being spatially
      proximal to the GUCX cleavage site of the substrate strand. Strong correlations
      were observed between colinear arrangement of stems I and III, constraints of
      base-pairing in the central core loop, and one particular placement of G(10.1)
      relative to the cleavage site. Our calculations of a stem-loop II-deleted
      ribozyme indicate that without needing to invoke any other constraints, the
      inherent asymmetry in the lengths of the two loop strands (3 nt in one and 7 nt
      in the other) that compose the core and flank G10.1-C11.1 stipulated strongly
      this particular G placement. This suggests that the hammerhead ribozyme maintains
      an asymmetry in its internal loop for a necessary structure/function reason.

PMID- 7567469
TI  - Detection of new genes in a bacterial genome using Markov models for three gene
      classes.
AB  - We further investigated the statistical features of the three classes of
      Escherichia coli genes that have been previously delineated by factorial
      correspondence analysis and dynamic clustering methods. A phased Markov model for
      a nucleotide sequence of each gene class was developed and employed for gene
      prediction using the GeneMark program. The protein-coding region prediction
      accuracy was determined for class-specific Markov models of different orders when
      the programs implementing these models were applied to gene sequences from the
      same or other classes. It is shown that at least two training sets and two
      program versions derived for different classes of E. coli genes are necessary in
      order to achieve a high accuracy of coding region prediction for uncharacterized
      sequences. Some annotated E. coli genes from Class I and Class III are shown to
      be spurious, whereas many open reading frames (ORFs) that have not been annotated
      in GenBank as genes are predicted to encode proteins. The amino acid sequences of
      the putative products of these ORFs initially did not show similarity to already
      known proteins. However, conserved regions have been identified in several of
      them by screening the latest entries in protein sequence databases and applying
      methods for motif search, while some other of these new genes have been
      identified in independent experiments.

PMID- 7567467
TI  - 5' upstream sequences of MyD88, an IL-6 primary response gene in M1 cells:
      detection of functional IRF-1 and Stat factors binding sites.
AB  - Transcription regulatory elements have been analyzed in upstream sequences of an
      Interleukin-6 (Il-6) primary response gene, MyD88. MyD88 2.3 kb mRNA is strongly
      and persistently induced in the course of myeloleukemic M1 cells differentiation
      with Il-6. MyD88 cDNA sequences were found in a region of 12 kb of mouse genomic
      DNA. Using Il-6 treated M1 cell RNAs, two transcription start sites have been
      localized, approximately 100 bp upstream from the 5' end of the cloned cDNA. We
      sequenced 1.4 kb of 5' genomic DNA including the first exon. In 5' of mRNA
      transcription start site, MyD88 nucleotidic sequence is 85% identical to 5'
      complementary sequences of the rat 3'-ketoacetyl CoA thiolase gene, over 1.2 kb.
      A DNA element conferring Il-6-inducible transcription to reporter genes, and
      localized 30 bp upstream of MyD88 first RNA start site, contains overlapping
      binding sites for cytokine activated transcription factors Stat and for the
      Interferon Regulatory Factor-1 and -2 (IRF-1 and IRF-2). In vitro binding assays
      showed that attachment of Stat factors to this element early in Il-6 treatment
      requires tyrosine kinase activation. IRF1, an activator of transcription, is also
      induced to bind to this sequence at later times. A model of persistent activation
      of MyD88 gene through these two types of factors is proposed.

PMID- 7567470
TI  - Structural changes in the 530 loop of Escherichia coli 16S rRNA in mutants with
      impaired translational fidelity.
AB  - The higher order structure of the functionally important 530 loop in Escherichia
      coli 16S rRNA was studied in mutants with single base changes at position 517,
      which significantly impair translational fidelity. The 530 loop has been proposed
      to interact with the EF-Tu-GTP-aatRNA ternary complex during decoding. The
      reactivity at G530, U531 and A532 to the chemical probes kethoxal, CMCT and DMS
      respectively was increased in the mutant 16S rRNA compared with the wild-type,
      suggesting a more open 530 loop structure in the mutant ribosomes. This was
      supported by oligonucleotide binding experiments in which probes complementary to
      positions 520-526 and 527-533, but not control probes, showed increased binding
      to the 517C mutant 70S ribosomes compared with the non-mutant control.
      Furthermore, enzymatic digestion of 70S ribosomes with RNase T1, specific for
      single-stranded RNA, substantially cleaved both wild-type and mutant rRNAs
      between G524 and C525, two of the nucleotides involved in the 530 loop
      pseudoknot. This site was also cleaved in the 517C mutant, but not wild-type
      rRNA, by RNase V1. Such a result is still consistent with a more open 530 loop
      structure in the mutant ribosomes, since RNase V1 can cut at appropriately
      stacked single-stranded regions of RNA. Together these data indicate that the
      517C mutant rRNA has a rather extensively unfolded 530 loop structure. Less
      extensive structural changes were found in mutants 517A and 517U, which caused
      less misreading. A correlation between the structural changes in the 530 loop and
      impaired translational accuracy is proposed.

PMID- 7567471
TI  - DNA determinants in sequence-specific recognition by XmaI endonuclease.
AB  - The XmaI endonuclease recognizes and cleaves the sequence C decreases CCGGG.
      Magnesium is required for catalysis, however, the enzyme forms stable, specific
      complexes with DNA in the absence of magnesium. An association constant of 1.2 x
      10(9)/M was estimated for the affinity of the enzyme for a specific 195 bp
      fragment. Competition assays revealed that the site-specific association constant
      represented an approximately 10(4)-fold increase in affinity over that for non
      cognate sites. Missing nucleoside analyses suggested an interaction of the enzyme
      with each of the cytosines and guanines within the recognition site. Recognition
      of each of the guanines was also indicated by dimethylsulfate interference
      footprinting assays. The phosphates 5' to the guanines within the recognition
      site appeared to be the major sites of interaction of XmaI with the sugar
      phosphate backbone. No significant interaction of the protein was observed with
      phosphates flanking the recognition sequence. Comparison of the footprinting
      patterns of XmaI with those of the neoschizomer SmaI (CCC decreases GGG) revealed
      that the two enzymes utilize the same DNA determinants in their specific
      interaction with the CCCGGG recognition site.

PMID- 7567472
TI  - Design, biochemical, biophysical and biological properties of cooperative
      antisense oligonucleotides.
AB  - Short oligonucleotides that can bind to adjacent sites on target mRNA sequences
      are designed and evaluated for their binding affinity and biological activity.
      Sequence-specific binding of short tandem oligonucleotides is compared with a
      full-length single oligonucleotide (21mer) that binds to the same target
      sequence. Two short oligonucleotides that bind without a base separation between
      their binding sites on the target bind cooperatively, while oligonucleotides that
      have a one or two base separation between the binding oligonucleotides do not.
      The binding affinity of the tandem oligonucleotides is improved by extending the
      ends of the two oligonucleotides with complementary sequences. These extended
      sequences form a duplex stem when both oligonucleotides bind to the target,
      resulting in a stable ternary complex. RNase H studies reveal that the
      cooperative oligonucleotides bind to the target RNA with sequence specificity. A
      short oligonucleotide (9mer) with one or two mismatches does not bind at the
      intended site, while longer oligonucleotides (21mers) with one or two mismatches
      still bind to the same site, as does a perfectly matched 21mer, and evoke RNase H
      activity. HIV-1 inhibition studies reveal an increase in activity of the
      cooperative oligonucleotide combinations as the length of the dimerization domain
      increases.

PMID- 7567473
TI  - Relative exon affinities and suboptimal splice site signals lead to non
      equivalence of two cassette exons.
AB  - Tau is a microtubule-associated protein whose transcript undergoes complex
      regulated splicing in the mammalian nervous system. Exons 2 and 3 of the gene are
      alternatively spliced cassettes in which exon 3 never appears independently of
      exon 2. Expression of tau minigene constructs in cells indicate that exon 2
      resembles a constitutive exon, while a suboptimal branch point connected to exon
      3 inhibits inclusion of exon 3 in the mRNA. Splicing of the two tau exons is
      controlled by their relative affinities for each other versus the affinities of
      their flanking exons for them.

PMID- 7567476
TI  - A simple method for preparing pools of synthetic oligonucleotides with random
      point deletions.

PMID- 7567475
TI  - Synthesis of 3H-labeled nucleoside-methyl[CT3]phosphonamidite and incorporation
      into methylphosphonate oligonucleotides for biodistribution and biostability
      studies.

PMID- 7567474
TI  - Suppression of c-myc oncogene expression by a polyamine-complexed triplex forming
      oligonucleotide in MCF-7 breast cancer cells.
AB  - Polyamines are excellent stabilizers of triplex DNA. Recent studies in our
      laboratory revealed a remarkable structural specificity of polyamines in the
      induction and stabilization of triplex DNA. 1,3-Diaminopropane (DAP) showed
      optimum efficacy amongst a series of synthetic diamines in stabilizing triplex
      DNA. To utilize the potential of this finding in developing an anti-gene strategy
      for breast cancer, we treated MCF-7 cells with a 37mer oligonucleotide to form
      triplex DNA in the up-stream regulatory region of the c-myc oncogene in the
      presence of DAP. As individual agents, the oligonucleotide and DAP did not
      downregulate c-myc mRNA in the presence of estradiol. Complexation of the
      oligonucleotide with 2 mM DAP reduced c-myc mRNA signal by 65% at 10 microM
      oligonucleotide concentration. In contrast, a control oligonucleotide had no
      significant effect on c-myc mRNA. The expression of c-fos oncogene was not
      significantly altered by the triplex forming oligonucleotide (TFO). DAP was
      internalized within 1 h of treatment; however, it had no significant effect on
      the level of natural polyamines. These data indicate that selective utilization
      of synthetic polyamines and TFOs might be an important strategy to develop anti
      gene-based therapeutic modalities for breast cancer.

PMID- 7567478
TI  - A micro-scale method to isolate DNA-binding proteins suitable for quantitative
      comparison of expression levels from transfected cells.

PMID- 7567477
TI  - Co-regulation of two gene activities by tetracycline via a bidirectional
      promoter.

PMID- 7567479
TI  - Efficient transfection of DNA by mixing cells in suspension with calcium
      phosphate.

PMID- 7567480
TI  - Under siege--again.

PMID- 7567481
TI  - Nurses under fire: the World War II experiences of nurses on Bataan and
      Corregidor. 1976.

PMID- 7567482
TI  - A strategy to assess the temporal dimension of pain in children and adolescents.
AB  - Two formats to enable children and adolescents to report the changing intensity,
      duration, and pattern of their pain were developed and tested: (a) a dot matrix
      with intensity markers on the y-axis and time markers on the x-axis and (b) a
      list of words or word phrases describing the temporal dimension of pain. Analyses
      of the dot matrix markings revealed six patterns of pain: steady decrease, steady
      increase, ongoing sharp increases and decreases, stair-step increase and
      decrease, steady increase and decrease, and constant. The 12 words and phrases
      described how pain began as well as how the pattern of pain changed over time.

PMID- 7567483
TI  - Nongenetic influences of obesity on risk factors for cardiovascular disease
      during two phases of development.
AB  - Matched-pair analyses of twins were used to examine nongenetic influences of
      obesity on the lipid profile and systolic and diastolic blood pressure (cross
      sectionally) during two phases of development--the school-age years (n = 73 twin
      pairs) and adolescence (n = 56 twin pairs)--and (longitudinally) in the
      transition between these two developmental phases. Data were collected during an
      early morning home visit. Results of the matched-pair t tests indicated
      significant environmental influences on obesity in both phases and in the
      transition (change in obesity) between these two phases. Intraindividual
      associations of obesity (kg/m3) and atherogenic lipids (total and LDL
      cholesterol) emerged during the school-age years. In adolescence, obesity was
      associated with HDL cholesterol and total triglyceride. Change in obesity (kg/m3)
      from the school-age years to adolescence was associated with total triglyceride.
      Results suggest an emphasis on obesity as part of CVD risk factor management in
      children and point to the importance of primary prevention early in life.

PMID- 7567484
TI  - The development of attachment behaviors in pregnant adolescents.
AB  - The development of attachment behaviors over time in a group of pregnant
      adolescents, ages 12 to 19, was investigated with Rubin's theoretical framework.
      Seventy-nine low-income pregnant adolescents enrolled in the study in their first
      trimester. Follow-up data were collected in the second and third trimesters (n =
      64 and 54, respectively) and after delivery (n = 47). Multivariate analysis,
      using profile analysis, indicated that maternal attachment in adolescents begins
      in pregnancy and increases over time, especially after quickening. Age-related
      differences were noted in the development of maternal-fetal attachment behaviors
      related to giving of self. Results showed a positive relationship between
      attachment in the third trimester and demonstration of affectionate behaviors
      toward the infant after birth. These findings are consistent with the theoretical
      framework.

PMID- 7567485
TI  - Staff nurses' career development relationships and self-reports of
      professionalism, job satisfaction, and intent to stay.
AB  - The purpose of this study was to investigate the range of career development
      relationships (CDRs) experienced by staff nurses in relation to the outcomes of
      professionalism, job satisfaction, and intent to stay. A sample of 390 Army staff
      nurses completed questionnaires measuring five CDRs--precepting, peer
      strategizing, coaching, sponsoring, and mentoring--and the outcome variables.
      Findings indicated that 61% of the sample experienced a CDR, with the predominant
      CDR being coaching. No CDR affected professionalism; however, job satisfaction
      and intent to stay may warrant further investigation in relation to CDRs. The
      findings suggest that if nurses perceived that an interest was taken in their
      career development, and felt valued by the developer, then usually staff nurses
      viewed the relationship as professionally important. The perception of importance
      often influenced intent to stay in a positive direction.

PMID- 7567486
TI  - The effects of postpartum depression on maternal-infant interaction: a meta
      analysis.
AB  - A meta-analysis of 19 studies was conducted to determine the magnitude of the
      effect of postpartum depression on maternal-infant interaction during the first
      year after delivery. Maternal-infant interaction was divided into three
      subcategories: maternal interactive behavior, infant interactive behavior, and
      dyadic interactive behavior. Substantive, methodological, and miscellaneous
      variables were extracted and coded by both the researcher and two research
      assistants. Combinations were calculated as unweighted, weighted by sample size,
      and weighted by the quality index score. Effects for maternal interactive
      behavior ranged from .32 to .36 for the r index, .68 to .78 for the d index, and
      .33 to .38 for the Fischer's Z. For infant interactive behavior, effects ranged
      from .35 to .38, .75 to .83, and .37 to .41 for the r, d, and Fisher's Z indexes,
      respectively. Effects for dyadic interactive behavior ranged from .47 to .50 for
      the r index, 1.07 to 1.15 for the d index, and .51 to .55 for Fisher's Z. Results
      of the meta-analysis indicate that postpartum depression has a moderate to large
      effect on maternal-infant interaction. Nursing interventions for depressed mother
      infant dyads during the first year after delivery are addressed.

PMID- 7567487
TI  - Metamemory and depression in cognitively impaired elders.
AB  - The purpose of this study was to examine the relationships of depression and
      health to the perceptions of memory capacity, change, locus, and strategy in
      cognitively impaired residents (N = 55) of nursing homes. All subjects had Mini
      Mental State Exam (MMSE) scores between 15 and 23. Subjects generally had low
      perceived health and mild depression. Pearson correlations between age and
      strategy (-.31), depression and capacity (-.44), and depression and change (-.41)
      aspects of metamemory were statistically significant. Division of impaired
      residents of nursing homes into cognitive level groups (mild and severe
      impairment) indicated significant group differences in use of over-the-counter
      medications, total memory strategies, and internal strategies. Overall, the set
      of variables accounted for 8% to 18% of the total variance in metamemory
      subscales.

PMID- 7567488
TI  - A comparison of three wound dressings in patients undergoing heart surgery.
AB  - Two hundred fifty patients undergoing heart surgery were randomized in a
      prospective comparative study of a semiocclusive hydroactive wound dressing, an
      occlusive hydrocolloid dressing, and a conventional absorbent dressing. The
      wounds were evaluated during the 4 weeks after surgery. Color photographs were
      used for a blind evaluation of wound healing. The conventional absorbent dressing
      was more effective in wound healing, compared with the hydroactive dressing.
      Further, there were fewer skin changes and less redness in the wounds with the
      conventional dressing than with the hydroactive dressing; the differences were
      not significant with the hydrocolloid dressing. The conventional dressing was
      less painful to remove than the hydroactive and hydrocolloid dressings. More
      frequent dressing changes, however, were needed when using the conventional
      dressing. Despite this, it was the least expensive alternative.

PMID- 7567489
TI  - Professional development. Pain. Knowledge for practice.

PMID- 7567490
TI  - The end result.

PMID- 7567492
TI  - Outside interests.

PMID- 7567491
TI  - Sun spots.

PMID- 7567493
TI  - Out of step.

PMID- 7567496
TI  - Confidence betrayed.

PMID- 7567494
TI  - Criminal negligence.

PMID- 7567498
TI  - Making sense of blood transfusion.
AB  - Nurses need to be alert to the risks inherent in blood transfusion. This paper
      outlines the observations and nursing interventions necessary during blood
      component therapy.

PMID- 7567495
TI  - Hepatitis B: immunising health workers and patients.
AB  - This paper describes the disease process and the implications for people working
      in at-risk occupations in the hope of increasing the awareness of the need for,
      and subsequent uptake of, vaccination programmes.

PMID- 7567497
TI  - Hepatitis C: a new enemy.
AB  - Nurses working in the field of substance misuse are aware of the risks of HIV and
      hepatitis B among individuals who indulge in high-risk behaviour. This paper
      highlights another danger to injecting drug users, that of hepatitis C, and
      argues that health professionals need to be aware of this and tailor their
      practice accordingly.

PMID- 7567499
TI  - How exercise can help people with mental health problems.
AB  - The researcher describes the outcomes gained by a young man with a diagnosis of
      chronic schizophrenia who participated in a 12-week progressive exercise
      programme. Using the Brief Psychiatric Rating Scale and the Nurses Observational
      Scale for Inpatient Evaluation, the researcher was able to evaluate any changes
      in the patient. There were significant changes in his psychological functioning,
      communication, animation, personal interest, motivation and insight into his body
      image. His physical fitness levels also improved and he showed less motor
      retardation and less body tension.

PMID- 7567500
TI  - Surveying the alternatives.

PMID- 7567501
TI  - Who was von Willebrand?

PMID- 7567502
TI  - Fringe medicine.

PMID- 7567503
TI  - Significant skills.

PMID- 7567504
TI  - Direction for the future.

PMID- 7567507
TI  - Professional development. Pain. The role of the nurse.

PMID- 7567505
TI  - Proof of value.

PMID- 7567506
TI  - Practical massage.

PMID- 7567508
TI  - Initiative to advise shoppers on continence.

PMID- 7567511
TI  - On duty. Interview by Ian McMillan.

PMID- 7567510
TI  - Open-door policy. Interview by Jane Cassidy.

PMID- 7567509
TI  - Big deal.

PMID- 7567512
TI  - Breaking the silence.

PMID- 7567513
TI  - Lifting the veil.

PMID- 7567514
TI  - In-patient sleep disturbance: the views of staff and patients.
AB  - It is generally recognised that sleep is necessary for the maintenance of well
      being and that the need for sleep increases with illness. The findings of a study
      on in-patient nights show that many do not believe they get sufficient sleep in
      hospital. Inadequate sleep may be because of discomfort worries and pain, or down
      to a variety of disturbances. The following paper proposes a number of approaches
      to tackling these issues.

PMID- 7567516
TI  - Insomnia and mental health.
AB  - The night care team's role in promoting mental health is not simply administering
      hypnotics. This paper describes the knowledge base needed and identifies several
      behavioural and cognitive strategies to aid patient empowerment.

PMID- 7567517
TI  - The thyroid gland 1.

PMID- 7567515
TI  - Unity now paramount.

PMID- 7567518
TI  - Psychological care in bone marrow transplantation.
AB  - This paper continues the series on haematological malignancies which began in the
      issue of August 2, and is the first of two papers looking at the psychological
      impact of bone marrow transplantation. It describes the psychological stages of
      bone marrow transplantation, the stresses and responses, as well as the patient's
      psychological reaction to isolation therapy.

PMID- 7567520
TI  - Getting your message across.

PMID- 7567519
TI  - Goffman, the individual, institutions and stigmatisation.
AB  - In the fifth part of our series about sociology, the sociology of Erving Goffman
      is discussed, particularly in relation to his work on institutions. In contrast
      with earlier prominent sociological figures, Goffman's emphasis was on the
      individual rather than on grand-scale theories about social systems.

PMID- 7567521
TI  - Living with kidney dialysis.

PMID- 7567522
TI  - Crisis? What crisis?

PMID- 7567523
TI  - Improved by degrees.

PMID- 7567524
TI  - Modules miss the point.

PMID- 7567525
TI  - Difficult bug to beat.

PMID- 7567526
TI  - Making a clean break.

PMID- 7567527
TI  - Professional development pain. Revision notes.

PMID- 7567528
TI  - Registering outrage.

PMID- 7567529
TI  - Practice makes perfect.

PMID- 7567530
TI  - Whistle while you work.

PMID- 7567531
TI  - Paper tigers?

PMID- 7567532
TI  - Tuberculosis: the history of incidence and treatment.

PMID- 7567533
TI  - TB: cure, care and control.
AB  - This paper looks at the treatment of TB and measures used to prevent the spread
      of disease. It highlights the role played by the health visitor or respiratory
      nurse within this essential public health service.

PMID- 7567534
TI  - Unity reaps rewards.

PMID- 7567535
TI  - The role of music therapy in the care of the newborn.
AB  - Music therapy may provide another way for care-givers to positively alter the
      sick neonate's environment. This article assesses some relevant literature on
      music's effects on the fetus and neonate, focusing on the critically sick
      newborn.

PMID- 7567536
TI  - Operative procedures for benign prostatic hypertrophy.

PMID- 7567537
TI  - Family therapy: concepts, models and applications.
AB  - Family therapy is a relatively new form of treatment in child and adolescent
      psychiatry. It developed from a clinical tradition of treating individuals into a
      model which actively addressed the family and wider context of symptom
      presentation. This article sets out some of the concepts underpinning this
      treatment. It reviews the three major models practised in the UK. It includes
      contemporary developments and critiques based on anti-oppressive and
      antidiscriminatory theory.

PMID- 7567538
TI  - Maternity care. Planning effects.

PMID- 7567540
TI  - Complementary medicine. Remedy for detox.

PMID- 7567539
TI  - Work versus home?

PMID- 7567541
TI  - Role reversal.

PMID- 7567542
TI  - Preparing to breathe alone.

PMID- 7567543
TI  - Nutritional demands.

PMID- 7567544
TI  - The needle and the damage done.

PMID- 7567549
TI  - Leading questions.

PMID- 7567546
TI  - Age-old problem.

PMID- 7567548
TI  - Commercial brake.

PMID- 7567545
TI  - Life support.

PMID- 7567547
TI  - Letter from Mexico.

PMID- 7567550
TI  - Dealing in hope.

PMID- 7567551
TI  - Pushing forward.

PMID- 7567553
TI  - The dream ticket.

PMID- 7567552
TI  - Lining up to leave.

PMID- 7567554
TI  - Evaluation of primary nursing in a nursing development unit.
AB  - This paper describes the method by which the staff team on a nursing development
      unit audited the way in which they organised the delivery of nursing care.
      Through the use of an established audit tool they were able to learn about their
      own practice as well offering a critique of the tool.

PMID- 7567557
TI  - Self-assessment of Project 2000 supervision.
AB  - This study explored the views of nurses on the important issues associated with
      their supervision of Project 2000 students. Small-group interviews took place
      with clinicians from medical, surgical and elderly-care areas in two large
      hospitals. The issues raised were then incorporated into a questionnaire which
      was distributed to Project 2000 supervisors. Satisfaction was generally expressed
      with preparatory courses, but there was a perceived lack of knowledge about the
      Project 2000 course. Practitioners enjoyed and felt capable of fulfilling their
      supervisory role. However, the numbers of students and the time needed were seen
      as problematic and left practitioners feeling responsible but poorly supported.
      More emphasis on communication between college and service personnel,
      particularly in respect of liaison and link functions, seems to be needed.

PMID- 7567555
TI  - Continence promotion in adults with learning disabilities.
AB  - Helping to reduce rates of incontinence among people with severe learning
      disabilities can have profound effects on their self-esteem and on unit running
      costs. This paper describes a hospital-based continence promotion programme for
      people with severe learning disabilities using a behavioural approach.

PMID- 7567556
TI  - Advances in the treatment of cystic fibrosis.
AB  - Cystic fibrosis is an autosomal recessive disease, characterised by pancreatic
      insufficiency, abnormal viscous mucus secretions and chronic respiratory tract
      infections. Treatment is with pancreatin preparations to improve intestinal
      digestion of food, but the use of high-potency products requires care. Postural
      drainage and other physiotherapeutic measures are essential to the relief of
      respiratory obstruction. A new approach to the respiratory problems of cystic
      fibrosis is dornase alpha, a mucolytic enzyme given by inhalation. Gene therapy
      may eventually provide the definitive answer to treatment and is already on the
      therapeutic horizon, but many practical problems remain to be solved.

PMID- 7567558
TI  - Basic facts.

PMID- 7567559
TI  - Unholy alliance.

PMID- 7567560
TI  - Surgical infection.

PMID- 7567562
TI  - Goal-setting aids care.

PMID- 7567561
TI  - Foot problems in diabetes.

PMID- 7567564
TI  - Fungating wounds.

PMID- 7567563
TI  - Care after burns injury.

PMID- 7567565
TI  - Cavity-wound management.

PMID- 7567566
TI  - Barriers and facilitators of research utilization. An integrative review.
AB  - For over 20 years, nursing literature has discussed the gap between the conduct
      of research and the use of its findings to improve practice. Factors relating to
      the nurse, the setting, the research, and the way research is presented have been
      identified as barriers to research utilization. A combined approach that includes
      specialty organizations that take the lead in knowledge synthesis and
      dissemination, the creation of national on-line databases, and enhanced
      institutional supports and educational efforts is recommended.

PMID- 7567567
TI  - Models and processes of research utilization.
AB  - The proliferation of research in nursing is greater today than at any other time
      in the history of nursing. In order for this research to be meaningful for
      practice, research utilization efforts are imperative. This article reviews three
      prominent research utilization models spanning three decades of development.
      Future challenges and suggestions for improving the process are identified.
      Through research utilization efforts, nurses are given the power to make informed
      choices regarding implementation of research-based assessments, diagnoses,
      interventions, and outcome measures that ultimately will result in improved
      patient outcomes.

PMID- 7567568
TI  - Evaluation of research-based nursing practice.
AB  - To determine the effectiveness of a research-based clinical intervention, a
      planned program of evaluation must be in place. The evaluation consists of two
      components: determining whether the intervention was implemented as intended and,
      if not, what barriers prevented the implementation; and determining whether the
      intervention produced the expected outcomes. Evaluation provides essential data
      for decision making and helps staff determine whether the intervention should be
      accepted, rejected, or modified for use in their setting. Research utilization
      activities complement QAI programs, and many patients benefit from new research
      based practice innovations. Through research utilization, clinical practice
      becomes vital to nursing research because clinical practice provides the testing
      ground for research findings. Knowledge generated under controlled situations is
      evaluated in the real world of clinical practice, and clinical data produced
      through evaluation provides a rationale for practice that can be meaningfully
      understood both inside and outside the nursing profession.

PMID- 7567569
TI  - Effective methods for disseminating research findings to nurses in practice.
AB  - Professionals in all disciplines are challenged by the proliferation of new
      knowledge. Nurses, too, must find cost-effective ways of ensuring that their
      patients are benefiting from the most current knowledge about health and illness.
      The methods of research dissemination to clinicians described in this article are
      presumed to be effective because of anecdotal reports, conference evaluations, or
      clinician surveys. The profession needs more sophisticated evaluations of the
      effectiveness of various dissemination methods. In the meantime, whether you are
      a researcher, an administrator, an educator, or a clinician, you have a role to
      play in improving research dissemination. Implement just one strategy from this
      article and evaluate the results. Each contribution moves nursing toward research
      based practice.

PMID- 7567570
TI  - Research utilization in a small, rural, community hospital.
AB  - Professional nursing organizations and nursing leaders value the importance of
      research-based nursing practice. The urgency for nurses to use research in
      practice applies to all, regardless of institution size. In this article, unique
      characteristics of small, rural, community hospital settings are described in
      relation to research utilization. The successful initiation and maintenance of a
      valued research utilization program in a small, rural hospital is presented, and
      suggestions on overcoming perceived barriers to the facilitation of research
      utilization activities are reviewed.

PMID- 7567571
TI  - Research utilization in a metropolitan children's hospital.
AB  - A model of research utilization directing clinical practice has been described.
      Clinical practice is conceptualized as a pyramid, with research knowledge forming
      the base. Department and unit-level activities are designed to promote the
      identification of research-based practices for incorporation into practice.
      Practice Committee structures are designed to facilitate the dissemination and
      utilization of research-based practices. This model has evolved over the past 10
      years, and current refinements include movement toward an interdisciplinary
      focus, support of unit level practice groups, and increased integration of the
      work of each practice committee.

PMID- 7567572
TI  - Enhancing research utilization by clinical nurse specialists.
AB  - A research utilization forum for clinical nurse specialists was initiated in the
      early 1990s in two service settings. The primary purpose of this voluntary, small
      group strategy was to help master's-prepared clinicians gain knowledge and skills
      regarding the systematic use of research findings. This article describes the
      forum strategy and its conceptual base. It also reviews outcomes related to
      program objectives, utilization competencies, and case reports of subsequent
      clinical nurse specialist research utilization behavior.

PMID- 7567575
TI  - Evaluation and implementation of a research-based falls assessment innovation.
AB  - The MFS is a research-based practice innovation designed to identify patients at
      risk for falling. With careful selection of falls cut-off scores, it offers an
      effective method for identifying most patients at risk for falling. Necessary
      frequency of falls assessment may vary among different populations. It is
      important to remember that a falls assessment instrument needs to be accompanied
      by a strong falls prevention program.

PMID- 7567573
TI  - Latex allergy precautions. A research-based protocol.
AB  - Recently, a number of case reports in the literature have heightened the
      awareness of health care professionals to the prevalence and seriousness of
      allergies to natural rubber latex. Reports of serious anaphylactic reactions in
      patients with no known history of the allergy are particularly alarming. The Iowa
      Model for improving quality through research utilization provided a framework to
      develop a protocol for screening patients and caring for those identified as high
      risk for a systemic reaction to latex. An overview of this research-based
      practice protocol and the process used are presented.

PMID- 7567574
TI  - The use of gauze versus transparent dressings for peripheral intravenous catheter
      sites.
AB  - The purpose of this research utilization project was to determine if a sufficient
      research base was present to support the use of gauze rather than transparent
      dressings for peripheral intravenous catheter sites. The research articles
      reviewed in this article do not support a relationship between dressing type and
      complications of peripheral intravenous catheters.

PMID- 7567576
TI  - Implementation of the Agency for Health Care Policy and Research postoperative
      pain management guideline.
AB  - The Agency for Health Care Policy and Research reviewed and synthesized the
      current pain research and developed a clinical practice guideline to assist the
      practitioner. A community hospital decided to adopt the postoperative pain
      management guideline using a research utilization approach. Education of health
      care professionals and development of a pain flow chart, pain scales, and updated
      technology were completed. Preliminary findings demonstrate a decreased pain
      intensity score postsurgically and an increase in patient satisfaction with staff
      response to pain relief.

PMID- 7567577
TI  - Animal-assisted therapy in the intensive care unit. A staff nurse's dream comes
      true.
AB  - This article presents an example of how one staff nurse was able to implement
      change in clinical practice on the basis of research. After reviewing the
      literature on AAT, I was able to implement this therapy for critically ill
      patients and families. Patient satisfaction surveys indicate that patients have
      benefited from this change. Patients report feelings of increased happiness,
      calmness, more feelings of love, and less loneliness. This example shows how
      staff nurses, a highly motivated and knowledgeable group, provide a fertile arena
      for bridging the research-practice gap.

PMID- 7567578
TI  - Using a research-based assessment scale in clinical practice.
AB  - The Braden Scale has been translated into Chinese, Japanese, Dutch, French,
      German, Italian, and perhaps other languages. It has been implemented in many
      health care settings in the United States and abroad. Perhaps the most
      significant data come from individual settings, such as the two highlighted
      earlier, which show that through use of a research-based risk assessment tool and
      a program of prevention based on the findings of the assessment, pressure ulcer
      incidence can be reduced. Both sites saw a 50% to 60% decrease in incidence of
      pressure sores. If the cost projections of Miller and Delozier cited earlier are
      correct and this decrease could be replicated in hospitals across the country,
      the cost savings for the nation would exceed $400 million.

PMID- 7567579
TI  - Adoption of a research-based practice for treatment of pressure ulcers.
AB  - Evaluation of a skin care protocol for the treatment of pressure ulcers in this
      institution showed that practitioners did adopt research-based practice. This
      change in practice was associated with a corresponding decrease in costs for
      treatment. More pressure ulcers received treatment after implementation of the
      protocol. Furthermore, the majority of pressure ulcers were being treated with
      wound care modalities identified by research as supportive of healing. Use of
      antiseptic agents harmful to the healing process declined as did use of topical
      agents with little research base to support their efficacy. The shift to practice
      patterns that were more consistent with research findings was associated with a
      corresponding decrease in costs for pressure ulcer treatment. Factors in this
      situation that lead to the positive outcome of knowledge utilization were an
      organizational model that promoted accountability of individual practitioners,
      staff participation in decision making, agency regard for research, and
      consultation with a nurse expert. Informal individual utilization of knowledge
      related to the treatment of pressure ulcers reinforced use of the research-based
      practice and expedited formal implementation of a policy/procedure related to
      their treatment. The process of knowledge utilization that occurred in this
      institution provides a prototype of how research can be translated into practice.
      Although limited to one specific clinical problem, the results of this process
      can be applied to any clinical condition where there are sufficient research
      findings to support development of recommendations for practice.

PMID- 7567580
TI  - The future of research utilization.
AB  - The need for utilization of scientifically based knowledge in clinical practice
      was recognized long ago. This article discusses the future of research
      utilization in nursing, emphasizing the role of nurse administrators, health care
      organizations, educational programs, and professional organizations. A futuristic
      view of research utilization is presented.

PMID- 7567581
TI  - A National Institute of Nursing Education. The Chandigarh model.

PMID- 7567582
TI  - Beliefs and practices of antenatal mothers in a rural setting.

PMID- 7567583
TI  - Cocaine abuse.

PMID- 7567584
TI  - Family bond for quality of life: nurses' concern.

PMID- 7567585
TI  - Pacing in dilated cardiomyopathy.

PMID- 7567586
TI  - Signal-averaged electrocardiography of the sinus and paced P wave in sinus node
      disease.
AB  - The detection of paroxysmal atrial fibrillation (AF) in patients requiring a
      permanent pacemaker for sinus node disease may influence the choice of both
      pacemaker and programmed mode. While signal-averaged ECG of the P wave (SAEP)
      during sinus rhythm may detect patients with paroxysmal AF, the value of SAEP in
      the presence of sinus node disease is unknown. We therefore evaluated SAEP in
      patients with sinus node disease during sinus rhythm and atrial pacing. We
      investigated 10 patients with sinus node disease alone (SND), 10 with sinus node
      disease and paroxysmal AF (SND-PAF), and 20 normal controls (NC) using a P wave
      specific, signal-averaging system. In sinus rhythm, duration and energy were
      greater in SND-PAF than in SND and NC (mean [SEM] duration: 153 [4] msec, 140 [4]
      msec, and 134 [2] msec, P < 0.001; energy from 20-150 Hz: 76 [18] muV2.sec, 48
      [7] muV2.sec, and 36 [3] muV2.sec, P = 0.006). Atrial pacing in SND-PAF produced
      an 11% prolongation of atrial activation but little further abnormality in P wave
      characteristics. In SND, atrial pacing caused a 20% prolongation of the P wave
      and increased P wave energy to a greater extent than in SND-PAF. We conclude that
      in patients with SND, atrial activation appears similar to normal controls during
      sinus rhythm but changes significantly on pacing. In patients with SND-PAF,
      atrial activation is abnormal during sinus rhythm with little further change when
      the atrium is paced. SAEP may be useful in detecting a predisposition to
      paroxysmal AF in the presence of sinus node disease and might help optimize
      pacemaker prescription.

PMID- 7567587
TI  - Comparison of biphasic and monophasic pulses: does the advantage of biphasic
      shocks depend on the waveshape?
AB  - With present implantable defibrillators, the ability to vary the defibrillation
      technique has been shown to increase the number of patients suitable for
      transvenous system. As newer waveforms become available, the need for a flexible
      device may change. In addition, although it has been shown that the option of
      biphasic waveform may increase the defibrillation efficacy, this may depend upon
      the shape of the biphasic waveform used. Thirty patients undergoing transvenous
      defibrillator implant were included in the study. In 20 patients (group I),
      defibrillation efficacy of simultaneous monophasic, sequential monophasic, and
      biphasic waveform with 50% tilt was determined randomly. Similarly, in ten
      patients (group II) testing of simultaneous monophasic shocks and biphasic
      waveforms with 65% and 80% tilt was performed in random order. The electrode
      system used consisted of two transvenous leads and a subcutaneous patch in all 30
      patients. In group I, 50% tilt biphasic waveform consistently provided similar or
      better defibrillation efficacy compared to monophasic waveforms (biphasic 7.5 +/-
      5.1 joules vs simultaneous 17 +/- 7.8 joules, P < 0.01; and vs sequential 17 +/-
      8.4 joules, P < 0.01). In group II, 65% tilt biphasic pulse required less energy
      for defibrillation as compared with simultaneous monophasic shocks (9.6 +/- 4.5
      joules vs 15.6 +/- 5.1 joules, P = 0.04). No significant difference was observed
      in terms of defibrillation threshold between 80% tilt biphasic shocks and
      simultaneous monophasic pulses (11.8 +/- 6 joules vs 15.6 +/- 5.1 joules, P =
      NS). Biphasic shocks with smaller tilt delivered using a triple lead system more
      uniformly improved defibrillation threshold over standard monophasic waveforms.

PMID- 7567588
TI  - Diurnal fluctuations in human ventricular and atrial refractoriness.
AB  - The relative significance of the direct and indirect effects of autonomic tone on
      diurnal fluctuations in human ventricular and atrial refractoriness are not well
      known. In this study, the circadian rhythms of ventricular and atrial effective
      refractory periods (ERPs) were measured by noninvasive programmed stimulation in
      ten patients (mean age 62 +/- 10 years) who had a permanent dual chamber
      pacemaker for complete atrioventricular (AV) block. The ERP was measured at 4
      hour intervals during spontaneous sinus rhythm with ventricular pacing (day 1)
      and during constant-rate dual chamber pacing (day 2). Cosinor analysis showed the
      ventricular ERP to have a significant diurnal rhythm in sinus rhythm (amplitude,
      12 msec; 95% confidence intervals 1-24 msec) but not during constant-rate pacing
      (amplitude, 4 msec; 95% confidence intervals -3-12 msec). The atrial ERP had a
      significant rhythm at times of both spontaneous sinus rate (amplitude, 19 msec;
      confidence intervals 13-24 msec) and constant heart rate (amplitude, 11 msec;
      confidence intervals 1-21 msec) with acrophase during the sleeping hours. The
      increase in heart rate during dual chamber pacing resulted in a more marked
      decrease in the average 24-hour ERP in the ventricle than in the atrium (46 +/- 9
      msec vs 12 +/- 6 msec, P < 0.01). Thus, refractoriness is more rate dependent in
      the ventricle than in the atrium, and autonomic influences on ventricular
      refractoriness are mainly indirect, via fluctuations in the sinus rate, but
      atrial refractoriness is also affected by direct neural influences and/or other
      rate independent factors.

PMID- 7567589
TI  - Prospective randomized comparison of biphasic waveform tilt using a unipolar
      defibrillation system.
AB  - BACKGROUND: A unipolar defibrillation system using a single right ventricular
      (RV) electrode and the active shell or container of an implantable cardioverter
      defibrillator situated in a left infraclavicular pocket has been shown to be as
      efficient in defibrillation as an epicardial lead system. Additional improvements
      in this system would have favorable practice implications and could derive from
      alterations in pulse waveform shape. The specific purpose of this study is to
      determine whether defibrillation efficacy can be improved further in humans by
      lowering biphasic waveform tilt. METHODS: We prospectively and randomly compared
      the defibrillation efficacy of a 50% and a 65% tilt asymmetric biphasic waveform
      using the unipolar defibrillation system in 15 consecutive cardiac arrest
      survivors prior to implantation of a presently available standard transvenous
      defibrillation system. The RV defibrillation electrode has a 5-cm coil located on
      a 10.5 French lead and was used as the anode. The system cathode was the active
      108 cm2 surface area shell (or "CAN") of a prototype titanium alloy pulse
      generator placed in the left infraclavicular pocket. The defibrillation pulse
      derived from a 120-microF capacitor and was delivered from RV-->CAN, with RV
      positive with respect to the CAN during the initial portion of the cycle.
      Defibrillation threshold (DFT) stored energy, delivered energy, leading edge
      voltage and current, pulse resistance, and pulse width were measured for both
      tilts examined. RESULTS: The unipolar single lead system, RV-->CAN, using a 65%
      tilt biphasic pulse resulted in a stored energy DFT of 8.7 +/- 5.7 J and a
      delivered energy DFT of 7.6 +/- 5.0 J. In all 15 patients, stored and delivered
      energy DFTs were < 20 J. The 50% tilt biphasic pulse resulted in a stored energy
      DFT of 8.2 +/- 5.4 J and a delivered energy DFT of 6.1 +/- 4.0 J; P = 0.69 and
      0.17, respectively. As with the 65% tilt pulse, all 15 patients had stored and
      delivered energy DFTs < 20 J. CONCLUSION: The unipolar single lead transvenous
      defibrillation system provides defibrillation at energy levels comparable to that
      reported with epicardial lead systems. This system is not improved by use of a
      50% tilt biphasic waveform instead of a standard 65% tilt biphasic pulse.

PMID- 7567590
TI  - The "low intensity treadmill exercise" protocol for appropriate rate adaptive
      programming of minute ventilation controlled pacemakers.
AB  - The objective of rate adaptive pacemakers that measure minute ventilation by
      transthoracic impedance is to simulate the physiological relationship of the
      sensed signal to the sinus node response during exercise, thus achieving an
      appropriate matching of heart rate with patient effort. The purpose of this study
      was to determine the physiological relationship between heart rate and minute
      ventilation (HR/VE) during peak exercise testing in order to develop a database
      for appropriate rate adaptive slope programming of minute ventilation controlled
      pacemakers. Due to several clinical limitations of peak exercise testing, it was
      additionally determined whether the 35-watt "low intensity treadmill exercise"
      (LITE) protocol can be used as a substitute for peak exercise test using the
      "ramping incremental treadmill exercise" (RITE) protocol in order to assess the
      correct HR/VE slope below the anaerobic threshold. The stress tests were
      performed on a treadmill with the collection of breath-by-breath gas exchange.
      Linear regression analysis was used to determine the HR/VE slope below and above
      the anaerobic threshold and during the early, dynamic phase of low intensity
      exercise with the RITE and LITE protocols, respectively. The results of this
      testing in 41 healthy subjects demonstrated that the HR/VE relationship
      throughout treadmill exercise using the RITE protocol was not linear but
      curvilinear in nature, with a steeper HR/VE slope of 1.54 +/- 0.51 below versus
      1.15 +/- 0.37 above the anaerobic threshold (P < 0.005). The HR/VE slope
      determined during the early, dynamic phase of the LITE protocol (1.58 +/- 0.88)
      did not differ from the HR/VE slope from rest to anaerobic threshold obtained
      using the peak exercise RITE test (1.54 +/- 0.51; P = 0.79). Rate adaptive pacing
      should simulate the curvilinear relationship between heart rate and minute
      ventilation from rest to peak exercise. The HR/VE slope determined during the
      early, dynamic phase of low intensity exercise represents the HR/VE slope derived
      from the RITE protocol below the anaerobic threshold. According to the peak
      exercise database, the slope above anaerobic threshold can easily be calculated
      as a percentage of the slope below the anaerobic threshold. The LITE protocol
      can, therefore, be effectively performed as a substitute for peak exercise stress
      tests to determine the correct pacemaker rate response factor in order to obtain
      a physiological heart rate to minute ventilation relationship for the appropriate
      matching of paced heart rate with patient effort.

PMID- 7567591
TI  - Radiofrequency catheter ablation of atriofascicular accessory pathways guided by
      discrete electrical potentials recorded at the tricuspid annulus.
AB  - BACKGROUND: The purpose of this study was to test the feasibility of using the
      recording of discrete electrical potentials to guide radiofrequency catheter
      ablation of atriofascicular accessory pathways with Mahaim-like properties.
      METHODS AND RESULTS: Four patients (3 females, 1 male) who fulfilled criteria for
      having atriofascicular accessory pathways with Mahaim-like properties and
      preexcited reciprocating tachycardia underwent radiofrequency catheter ablation.
      The mean age was 35 years (range 27-47). Symptoms were present for a mean of 10.5
      years (range 6-18). Recording of discrete electrical potentials of the
      atriofascicular pathway was attempted by mapping the tricuspid annulus in sinus
      rhythm, during atrial pacing, and during reciprocating tachycardia. During atrial
      pacing, a mean of seven radiofrequency pulses (range 1-14), delivered to the
      tricuspid annulus at the area where electrical potentials were recorded,
      eliminated conduction through the atriofascicular accessory pathway in all
      patients. No complications occurred. Tachycardia did not reoccur during a mean
      follow-up of 5 months (range 3-9). CONCLUSIONS: Recording of discrete electrical
      potentials at the tricuspid annulus identifies an optimal ablation site where
      radiofrequency current can safely eliminate conduction through atriofascicular
      accessory pathways with Mahaim-like properties.

PMID- 7567592
TI  - Reproducibility of electrophysiological testing during antiarrhythmic therapy for
      ventricular arrhythmias unrelated to coronary artery disease.
AB  - Although electrophysiological studies are commonly used in the management of
      patients with ventricular tachycardia (VT), the reproducibility of these studies
      during therapy has not been established in patients in whom VT is associated with
      conditions other than coronary artery disease. Therefore, we performed
      confirmation studies during drug therapy in 60 patients (mean age 48 +/- 18
      years; 41 male) with sustained ventricular arrhythmias induced during initial
      study to assess the reproducibility of drug effect. The stimulation protocol used
      included the serial introduction of up to three premature ventricular stimuli
      during sinus rhythm and with ventricular pacing at two pacing rates. Rapid
      ventricular pacing techniques were also used. Antiarrhythmic drug efficacy was
      confirmed in 78% of patients. Sustained VT was induced at repeat
      electrophysiological study in 18% of patients during antiarrhythmic therapy that
      had been felt to be effective on the basis of a single drug study. We conclude
      that electrophysiological study results during antiarrhythmic therapy exhibit
      significant day-to-day variability. Sustained VT can be induced during
      antiarrhythmic therapy previously determined to be effective by
      electrophysiological techniques in many patients.

PMID- 7567593
TI  - Continuous heart rate variability monitoring through complex demodulation
      implemented with the fast Fourier transform and its inverse.
AB  - A new method for the analysis of 24-hour heart rate variability (HRV) using
      complex demodulation (CDM) implemented with the fast Fourier transform (FFT) and
      its inverse is described. In a control group with palpitations and dizzy spells
      (n = 30, 47.2 +/- 16.7 years) the relationship between HRV parameters and subject
      age was investigated. CDM was used to obtain the amplitude and frequency of the
      low frequency (LF) and high frequency (HF) oscillations for 8 diurnal hours and 4
      nocturnal hours. Differences between the two periods were seen in the LF/HF ratio
      (2.2 +/- 0.6 vs 1.5 +/- 0.6; P < 0.0001), HF amplitudes (12 +/- 6 vs 17 +/- 7
      normalized units, P < 0.05), and in the mean frequency of the LF oscillations
      (0.078 +/- 0.008 vs 0.073 +/- 0.007 Hz, P < 0.01). During the daytime, age was
      inversely correlated to HF amplitude (r = -0.60), directly correlated to HF mean
      central frequency (r = 0.40), inversely correlated to LF amplitude (r = -0.55),
      and likewise inversely correlated to LF mean central frequency (r = -0.74, P <
      0.001). At night, age was only inversely correlated to HF amplitude and to LF
      mean central frequency. CONCLUSIONS: Continuous HRV monitoring through CDM
      implemented with the FFT and its inverse differentiates the periods of diurnal
      activity and nocturnal rest as an expression of two different activity states of
      the autonomic nervous system. It allows nonstationary analysis, and separately
      provides mean and instantaneous oscillation amplitude and frequency. Subject age
      is not equally related to mean amplitude and frequency of a given oscillation.

PMID- 7567594
TI  - The impact of the implantable cardioverter defibrillator on quality-of-life.
AB  - The implantable cardioverter defibrillator (ICD) is an established treatment for
      patients with life-threatening ventricular arrhythmias. While it clearly reduces
      the incidence of death from recurrent arrhythmia, little is known about the
      impact on patients' quality-of-life. In this prospective study, quality-of-life
      was assessed by questionnaire before and after ICD implantation. The "Sickness
      Impact Profile" (SIP), which evaluates physical, psychosocial, and other
      activities, as well as functions of daily life, was used. Employment and
      rehospitalization rates were also examined. Twenty-one of 23 consecutive
      patients, aged 58 +/- 11 years, undergoing ICD implantation at Royal Perth
      Hospital were studied. During the 14 +/- 8 month follow-up, 4 patients died.
      Functional capacity was unchanged in all but one of the survivors in whom it
      improved from New York Heart Association Class III to II. Four of 8 survivors
      employed before implant have since retired. Six patients required
      rehospitalization on 13 occasions, problems related to arrhythmias or the ICD.
      Overall SIP scores preimplant (11.2 +/- 9.3; P < 0.05) were significantly worse
      at 6-month follow-up (21.7 +/- 18.2), but returned to preimplant levels by 12
      month follow-up (8.8 +/- 10.8; NS). This was primarily due to transient problems
      in the areas of emotional behavior, alertness, and social interaction. SIP
      psychosocial dimension scores: preimplant: 7.2 +/- 9.0; 6-month: 17.8 +/- 18.1 (P
      < 0.05); and 12-month: 8.6 +/- 10.3 (NS). Early retirement and hospitalizations
      due to arrhythmias may still be expected even after implantation of an ICD;
      however, quality-of-life appears only to temporarily decline.

PMID- 7567596
TI  - Bundle branch reentry ventricular tachycardia.

PMID- 7567597
TI  - The World-Wide Web.

PMID- 7567595
TI  - Plasma catecholamines and cyclic AMP response during head-up tilt test in
      patients with neurocardiogenic (vasodepressor) syncope.
AB  - To examine hemodynamic, plasma catecholamines, and cyclic AMP changes during tilt
      in patients with neurocardiogenic (vasodepressor) syncope, six patients underwent
      80 degrees head-up tilt test for 10 minutes with isoproterenol infusion (1-3
      micrograms/min). Venous blood was sampled in the supine position, at 3 minutes of
      tilt, and at the onset of vasodepressor reaction during tilt. All patients had
      previous tilt studies in which vasodepressor syncope had been induced
      reproducibly (mean 3.3 episodes in each patient). Syncope was induced at 6.1 +/-
      0.4 minutes of tilt with an infusion of isoproterenol (mean 1.7 +/- 0.3
      micrograms/min). Although arterial pressure and heart rate did not change
      significantly between in the supine position and at 3 minutes of tilt, plasma
      norepinephrine increased significantly at 3 minutes of tilt (0.44 +/- 0.10 ng/mL;
      P < 0.05) and at the onset of vasodepressor reaction (0.49 +/- 0.12 ng/mL; P <
      0.01) compared to the supine position with isoproterenol (0.34 +/- 0.10 ng/mL).
      Also, cyclic AMP (cAMP) increased significantly at 3 minutes of tilt (25.3 +/-
      2.0 pmol/mL; P < 0.005) and at the onset of vasodepressor reaction (29.6 +/- 1.7
      pmol/mL; P < 0.005) compared to the supine position with isoproterenol (20.4 +/-
      1.9 pmol/mL). After administration of selective beta 1-blocker, metoprolol (40
      mg/day), plasma norepinephrine, and cAMP during tilt did not change significantly
      compared to baseline tilt. However, metoprolol prevented the syncope in 3 of 6
      patients. After administration of beta 1-, beta 2-blocker, propranolol (30
      mg/day), cAMP at 3 minutes of tilt decreased significantly compared to the
      baseline tilt (16.9 +/- 1.4 pmol/mL vs 25.3 +/- 2.0 pmol/mL; P < 0.05) and
      propranolol prevented the syncope in all six patients. We concluded that the
      increase of cAMP may play an important role for the induction of vasodepressor
      reaction in patients with neurocardiogenic (vasodepressor) syncope. The
      concentration of cAMP showed more sensitive response to vasodepressor reaction
      than that of norepinephrine.

PMID- 7567599
TI  - A case of rate dependent accessory pathway conduction.

PMID- 7567598
TI  - Regulated to death: the matter of informed consent for human experimentation in
      emergency resuscitation research.

PMID- 7567600
TI  - Relief of left ventricular outflow tract obstruction following inadvertent left
      ventricular apical pacing in a patient with hypertrophic cardiomyopathy.
AB  - Dual chamber (DDD) pacing improves symptoms and relieves left ventricular (LV)
      outflow obstruction in hypertrophic cardiomyopathy. The ventricular lead is
      usually positioned at the right ventricular apex (RVA). We report a patient in
      whom the ventricular lead had inadvertently penetrated the septum, resulting in
      DDD pacing from the LV apex. However, after 3 months, obstruction was reduced and
      symptoms were improved. Pacing from LV apex and RVA resulted in comparable
      hemodynamic improvement. This case suggests that the asynchronous wave of septal
      contraction, originating from the apex, irrespective of ventricular site,
      accounts for the reduction in LV outflow obstruction.

PMID- 7567601
TI  - Treatment of malignant neurocardiogenic syncope with dual chamber cardiac pacing
      and fluoxetine hydrochloride.

PMID- 7567602
TI  - Inconsistent response to rapid atrial rhythms in a DDD pacemaker with the
      fallback feature.
AB  - Dual chamber pacing may be problematic in patients with paroxysmal atrial
      arrhythmias. The fallback feature has been incorporated into some devices to
      avoid tracking of rapid atrial rhythms. A case is reported in which the
      initiation of fallback was inconsistent during paroxysms of atrial flutter.
      Evaluation of the ventricular output of an isolated device in response to various
      applied atrial rates revealed that fallback occurred consistently only when
      2xTARP (ms) < or = URL (ms).

PMID- 7567603
TI  - Catheter ablation in a less privileged country: the importance of spreading the
      goods.

PMID- 7567606
TI  - Shorter hospital stays necessitate changes in breast cancer patient education.

PMID- 7567604
TI  - Defibrillation, either in clinical practice or in basic and applied research,
      uses mainly energy (expressed by and large in joules) as the reference parameter
      to dose the discharge or to describe thresholds.

PMID- 7567605
TI  - STIMAREC report.

PMID- 7567607
TI  - Readers comment on the nursing role in cancer genetics.

PMID- 7567608
TI  - The healing power of story.

PMID- 7567609
TI  - Do you like the things that life is showing you? The sensitive self-image of the
      person with cancer.

PMID- 7567611
TI  - Believing and dreaming to improve cancer care.

PMID- 7567610
TI  - Quality of life in long-term cancer survivors.
AB  - PURPOSE/OBJECTIVES: To describe the quality of life (QOL) of long-term cancer
      survivors. DESIGN: Descriptive, mailed survey. SETTING: Membership of the
      National Coalition for Cancer Survivorship (NCCS), which is a nonprofit, peer
      support network for people living with cancer. SAMPLE: 687 (57%) of the 1,200
      members of NCCS completed the survey. The mean age of the sample was 49.6 years;
      81% were female. The predominant cancer diagnoses were breast (43%), lymphoma
      (9%), ovarian (8%), and Hodgkin's disease (8%). METHODS: Mailed survey using
      three instruments: a demographic tool, the Quality of Life-Cancer Survivors (QOL
      CS) tool, and the Functional Assessment of Cancer Therapy-General (FACT-G) tool.
      MAIN RESEARCH VARIABLES: Subscale and individual items of QOL including physical,
      psychological, social, and spiritual well-being. FINDINGS: Results include areas
      of positive effects for cancer survivors and continued demands of survivorship.
      Based on scoring of 0 (worst outcome) to 10 (best outcome), cancer survivors'
      mean QOL-CS subscores were 5.88 for psychological well-being, 6.59 for spiritual
      well-being, 6.62 for social well-being, and 7.78 for physical well-being. Several
      demographic factors (e.g., evidence of active disease; female gender; presence of
      spouse/partner or children; length of time since diagnosis; income) had
      significant influence on QOL. CONCLUSIONS: Cancer survivors experienced altered
      lives and had needs related to fear of recurrence and facing the spiritual
      aspects of having survived a life-threatening illness. IMPLICATIONS FOR NURSING
      PRACTICE: The growing population of cancer survivors has long-term needs for
      nursing care that address multidimensional aspects of QOL.

PMID- 7567612
TI  - Balancing our lives: a study of the married couple's experience with breast
      cancer recurrence.
AB  - PURPOSE/OBJECTIVES: To examine the married couple's experience with breast cancer
      recurrence from each partner's own perspective, to describe their mood and
      martial quality, and to develop an initial explanatory theory of the couple's
      lived experience with breast cancer recurrence. DESIGN: Descriptive, qualitative.
      SETTING: Homes of married couples in the Pacific Northwestern United States.
      SAMPLES: 15 married couples comprised of women diagnosed with recurrent breast
      cancer and their husbands. The median length of time since recurrence was 10
      months. METHODS: Structured interviews were conducted in the homes of married
      couples that met eligibility criteria using an open-ended interview schedule, the
      Marital Dyad Interview, and two standardized questionnaires-the Spanier Dyadic
      Adjustment Scale and the Center for Epidemiological Studies Depression Scale.
      MAIN RESEARCH VARIABLES: Lived experience of couples to breast cancer recurrence,
      depressed mood, and marital adjustment. FINDINGS: BALANCING OUR LIVES was the
      core category that explained how the couples lived with the breast cancer
      recurrence. Couples actively worked to balance their lives by keeping the breast
      cancer a background, not a foreground, issue. Although couples talked about
      managing the daily realities of the woman's breast cancer, not dwelling on the
      cancer and moving ahead and healing themselves was most important. Balancing Our
      Lives involved the couples in four major processes: managing the woman's everyday
      illness, surviving, healing, and preparing for death. Concurrently, one or both
      members of 60% of the couples scored outside the normative range on either
      depressed mood or marital adjustment. CONCLUSIONS: The couples' ways of managing
      the breast cancer recurrence through balancing their lives may be facilitating
      their behavioral functioning but may not be enhancing their mood or marital
      quality. IMPLICATIONS FOR NURSING PRACTICE: The couples' management of recurrence
      may benefit from additional strategies, including helping them work through sad
      thoughts or feelings instead of avoiding them; recognizing and supporting each
      other's views, even when their views differ; and helping them to learn ways to
      express sad thoughts and feelings without overly dwelling on them.

PMID- 7567613
TI  - Definition and measurement of quality of life in oncology nursing research:
      review and theoretical implications.
AB  - PURPOSE: To describe oncology nurses' diverse conceptual and operational
      approaches to the study of quality of life (QOL) by reviewing oncology nursing
      research of QOL, using principles of theory-building to examine and explain
      findings, and discussing implications for QOL measurement in research and
      practice. DATA SOURCES: Journal articles published since 1980. DATA SYNTHESIS:
      The use of diverse definitions and measures of QOL reflects the difficulty of
      operationalizing this abstract and highly individualized concept. A predominant
      trend in nursing research is the development of multidimensional scales that are
      disease-specific and include respondent-generated items. CONCLUSIONS: Findings
      reflect a struggle to balance the need for practical, clinically relevant
      measures of QOL with the equally important need for theoretical integrity and
      comprehensiveness. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to examine
      carefully their purposes for documenting QOL and the congruence of the evaluation
      method with patients' perceptions of QOL. This information can guide the choice
      of methods and enhance the validity of data used to evaluate QOL.

PMID- 7567614
TI  - Validity and reliability of an oncology critical care patient acuity tool.
AB  - PURPOSE/OBJECTIVES: To test the reliability and validity of a patient acuity tool
      for use on a critical care oncology unit. DESIGN: Prototype classification system
      using therapeutic indicators to describe a patient's acuity. SETTING: Intensive
      care unit of a research and academic oncology hospital in the Southeastern United
      States. SAMPLE: Critical care nursing staff including management-level personnel
      at the research site. METHODS: An acuity tool for critical care was developed
      using the Johns Hopkins Oncology Center's patient classification system as a
      model. Content validity indexes were calculated based on ratings of nurse
      experts. interrater reliability was calculated based on two independent raters: a
      staff nurse and a patient care manager. MAIN RESEARCH VARIABLES: Appropriateness
      of language and categorization of therapeutic indicators developed for the tool.
      FINDINGS: The content validity index of the entire tool was 0.85; 24/25
      indicators were retained. Reliability was r = 0.84. CONCLUSIONS: The tool is
      reliable and valid. IMPLICATIONS FOR NURSING PRACTICE: Acuity tools can be used
      to calculate unit productivity and assist with determination of staffing needs.
      In this age of healthcare reform, it is imperative that personpower needs in all
      care settings be accurately determined to provide cost-effective and safe care
      levels.

PMID- 7567617
TI  - Home care for pain, odor, and drainage in tumor-associated wounds.

PMID- 7567616
TI  - A flow sheet for follow-up after chemotherapy extravasation.
AB  - PURPOSE/OBJECTIVES: To introduce and describe the development and implementation
      of a flow sheet used to document patient follow-up after chemotherapy
      extravasation. DATA SOURCES: Published articles, institutional standards of
      nursing practice, and the Oncology Nursing Society Cancer Chemotherapy
      Guidelines. DATA SYNTHESIS: Extravasation is a potentially serious and severe
      complication of vesicant chemotherapy administration. A tool was designed to
      streamline documentation of patient symptoms, nursing interventions, patient
      education, and follow-up care after a suspected or actual extravasation.
      CONCLUSIONS: The flow sheet improves nursing documentation after a suspected or
      actual vesicant chemotherapy extravasation and provides a consistent, concise
      method for monitoring extravasations over time. IMPLICATIONS FOR NURSING
      PRACTICE: The flow sheet standardizes nursing assessment, intervention, patient
      education, and follow-up care after a suspected or actual chemotherapy
      extravasation. Use of the flow sheet saves time and improves consistency of
      nursing documentation.

PMID- 7567615
TI  - Perceived concerns of pregnant women with breast cancer treated with
      chemotherapy.
AB  - PURPOSE/OBJECTIVES: To identify concerns of women who had received chemotherapy
      for breast cancer while pregnant. DESIGN: Exploratory, descriptive, retrospective
      pilot study. SETTING: Large cancer center in the Southwestern United States.
      SAMPLE: Six women (mean age of 35.5 years) who had been treated for breast cancer
      while pregnant within the previous five years. METHODS: Mailed survey using a
      demographic form and the Bandyk Concerns Questionnaire--a 30-item Likert-type
      scale. MAIN RESEARCH VARIABLES: Concerns about the effects of breast cancer
      treatment on the pregnancy and the fetus. FINDINGS: The primary concern was
      "living to see my child grow up." Of least concern was "other people's opinion of
      me." CONCLUSIONS: Although an informational pamphlet was written based on these
      results, more extensive examination of the special group of patients is needed to
      draw any conclusions. IMPLICATIONS FOR NURSING PRACTICE: Nurses are in a good
      position to offer accurate information to women who must make the choices
      involved with receiving chemotherapy during pregnancy and to support the women
      during and after the treatment and the child's birth.

PMID- 7567618
TI  - Using metronidazole (Flagyl) for odor control.

PMID- 7567619
TI  - Controlling odors in malignant ulcerating lesions.

PMID- 7567620
TI  - Reducing odor caused by metastatic breast cancer skin lesions.

PMID- 7567621
TI  - Creating a comfortable neck wound dressing.

PMID- 7567622
TI  - Skin care for patients receiving radiation.

PMID- 7567624
TI  - Improving care of pressure sores.

PMID- 7567623
TI  - Using vitamin A + D Ointment for wounds.

PMID- 7567625
TI  - Interventions for a progressing head and neck tumor.

PMID- 7567626
TI  - Restoring interproximal caries.

PMID- 7567627
TI  - Pediatric dentistry in care of the cancer patient.

PMID- 7567629
TI  - Cancer of bone in children.

PMID- 7567628
TI  - Soft tissue sarcomas.

PMID- 7567630
TI  - Neuroblastoma and brain tumors in childhood.

PMID- 7567631
TI  - Late effects of cancer treatment in children.

PMID- 7567632
TI  - The past and future of cancer in the young.

PMID- 7567633
TI  - Pediatric bone marrow transplantation.

PMID- 7567634
TI  - Differential diagnosis of oral enlargements in children.
AB  - The purpose of this article is to review soft tissue and bony enlargements that
      typically occur in the oral and perioral region of children. In order to organize
      these lesions into a thorough but comprehensible format, the principles of
      differential diagnosis must be used. All oral enlargements are broadly classified
      as soft tissue or bony abnormalities. Determination of the specific lesion
      category is based primarily on a prominent feature that demonstrates the nature
      of the lesion, followed by the secondary clinical features and any contributory
      patient information. Classification of exophytic soft tissue entities includes:
      papillary surface enlargements, acute inflammatory enlargements, reactive
      hyperplasias, benign submucosal cysts and neoplasms, and aggressive and malignant
      neoplasms. Bony enlargements of the maxilla and mandible are divided into three
      categories: inflammatory lesions, benign cystic and neoplastic lesions, and
      aggressive and malignant lesions. This extensive topic is summarized on flow
      charts for easy reference with emphasis on grouping together lesions with common
      characteristics.

PMID- 7567635
TI  - Evaluation of a no-rinse enamel conditioning prior to sealant application: an in
      vitro study of comparison to traditional etching technique.
AB  - Moisture contamination is a major factor in sealant application, often
      determining clinical success or failure. A new enamel conditioner using HNO3
      (2.5%) has been introduced that does not require a water rinse after etching. The
      aim of this study is to compare etching characteristics using sealant retention
      from shear bond strength tests for traditional etch conditioning using H3PO4
      (37%) and the HNO3 (2.5%) conditioner with and without a water rinse. We used 28
      crown-intact extracted human teeth. We evaluated eight shear bond strength tests
      per group, on cylindrical sealant stubs (3.24 mm diameter x 3 mm height) for 12
      groups (three etch conditions, two prophylactic methods, and two enamel surface
      type). The highest mean values of shear bond strength of 22.0 MPa was measured
      for H3PO4, and the lowest of 12.7 MPa for HNO3 (2.5%) without water wash. No
      significant differences (P < 0.05) were found between water rinse and air blast
      post-treatment groups after HNO3 conditioning.

PMID- 7567638
TI  - [How best to perform aerosol therapy. 2. Drugs].
AB  - The individuation of a 5:1 ratio for the posology of beta 2-agonist drugs
      administered respectively by nebulizer or as a spray plus a spacer, allows the
      use of these drugs by the latter way also during an acute attack of bronchospasm.
      Other qualifying aspects of beta 2-agonist are the possibility of increasing the
      dose up to a continuous administration in case of a severe attack of
      bronchoconstriction and the demonstrated clinical efficacy of these drugs during
      the first year of life. The question of the correct dose to administer according
      to the age of the patient appears to be rather complex: in fact if on the one
      hand during the first months of life the low tidal volume (VT) can reduce the
      quantity of drug inhaled, on the other the low pulmonary volumes (FRC) of the
      first years of life determine a lesser dilution of the inhaled drug and therefore
      a greater pulmonary concentrations. Among corticosteroids for inhalation, the
      ones with the fewer side effects should be chosen: these may appear although in a
      subclinical fashion at relatively low doses of about 400 micrograms/day of
      beclomethasone. The most frequent indication for an antibiotic treatment by
      inhalation is represented by chronic pulmonary infection caused by bacteria
      sensible only to parenteral antibiotics (for ex. Pseudomonas infection in cystic
      fibrosis). The extremely high cost of these treatments requires the use of
      devices with a very high efficiency, in other words capable of nebulizing very
      large percentages of drug into small particles (< 6 microns).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7567636
TI  - Water and formula fluoride concentrations: significance for infants fed formula.
AB  - The independent contributions of formula and water to the total fluoride (F)
      intake from the diet of formula-fed infants is not fully documented. Although the
      precise timing and mechanism by which dental fluorosis occurs has not been fully
      defined, water F levels can be an important consideration in the risk of dental
      fluorosis for formula-fed infants. An assessment of 1,308 participants younger
      than 2 years old revealed that: 81% of homes received public water; 19% received
      well water; 26% of participants used bottled water; and 11% used some kind of
      filtration system. In this study, virtually all formulas consumed by the birth
      cohort and water sources used in the reconstitution of these formulas were
      assayed for F using a F ion specific electrode and direct read method, except for
      soy-based formulas, which were analyzed by microdiffusion (modified Taves). Among
      78 commercially available bottled waters in Iowa, F levels ranged from 0.02 to
      1.36 ppm (mean 0.18 ppm), 83% from 0.02 to 0.16 ppm, 7% from 0.34 to 0.56 ppm, 1%
      had a F level of 0.88, and 9% had F levels > 1.0 ppm. Among 47 casein (milk)
      based formulas, 16 ready-to-feed (RTF) formulas had levels of 0.04-0.55 ppm F
      (mean 0.17 ppm), 14 liquid concentrates (LC) reconstituted with distilled water
      had levels of 0.04-0.19 ppm F (mean 0.12 ppm), and 17 powdered concentrates (PC)
      reconstituted with distilled water had levels of 0.05-0.28 ppm F (mean 0.14 ppm).
      The 17 soy-based formulas had a range of 0.04-0.47 ppm F (mean 0.26
      ppm).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567640
TI  - [Neonatal characteristics in the physiopathology of shock].
AB  - In this work we tried to analyse the different factors which cooperate to produce
      and maintain a shock condition; we considered in particular pathophysiology and
      haemodynamic features of the different types of shock and the pathophysiology of
      MOSF (multiple systems organ failure). Furthermore, we remembered peculiarities
      and effects of the "reperfusion syndrome" which can occur after cardiopulmonary
      resuscitation of the patient due to superoxides. Finally we outlined the
      substantial and significant differences between newborn and not newborn
      concerning the haemodynamic responses and the cardiocirculatory management in the
      newborn during shock treatment.

PMID- 7567637
TI  - Looking a gift horse in the mouth: effects of cornstarch therapy and other
      implications of glycogen storage disease on oral hygiene and dentition.

PMID- 7567642
TI  - [The lipid status, insulinemia and fat mass in 40 children with essential
      obesity].
AB  - Obesity is usually defined on the basis of body composition measurements. Body
      composition can be assessed using elaborate methods or anthropometry. Obese
      children are characterized by increased serum total cholesterol and
      triglycerides, reduced high-density-lipoprotein(HDL)-cholesterol concentrations,
      and hyperinsulinemia. Such a metabolic profile may create favorable conditions
      for atherogenesis and cardiovascular disease later in life. In fourty obese
      children aged 6-14 years were evaluated plasma insulin after OGTT, serum lipids
      and body composition. The correlation analysis between insulin, lipids and fat
      mass (%), based on skinfold measurements was not significative. These results are
      possible because with skinfold measurements are not separated the subcutaneous
      and intraabdominal compartments; infarct, only abdominal obesity is associated
      with the increased risk factors (hyperinsulinemia, hyperlipidemia, ecc.).

PMID- 7567639
TI  - [The primary and secondary prevention of allergic diseases in the child "at risk"
      for atopy: a review of the literature and the authors' personal experience].
AB  - The increasing prevalence of the atopic diseases in the industrialized countries
      is closely linked together the numerous efforts to attempt to prevent them.
      Several Authors have suggested environmental and/or dietetic measures in the "at
      risk" babies in the first months of life, more critical for the atopy
      development. The environmental measures are directed to the avoidance of the
      major inhalant allergens (house dust mite, pet allergens, cigarette smoking,
      etc.). The employment of the acaricides can be useful to this purpose. The
      dietetic measures include: prolonged and exclusive breast feeding in the first
      six months of life, delayed and gradual weaning, avoidance of the major food
      allergens (cow's milk proteins, egg, fish, etc.) for the breast-feeding mother,
      choice of an adequate cow's milk substitute when the breast-feeding is not
      sufficient. For long time soya milk has been employed. In the last decade
      partially or highly hydrolyzed formulae were introduced, but in some cases they
      can be more allergenic of cow's milk. In this paper we reviewed the various
      environmental and dietetic measures and the different prevention programs that
      the several Authors have adopted in "at risk" babies.

PMID- 7567641
TI  - [The role of transforming growth factor-beta (TGF-beta) in the pathogenesis of
      primary megaureter. A histological and immunocytochemical study].
AB  - Histologic and Transforming Growth Factor Beta (TGF-beta) immunostain patterns
      were sought in resected distal urinary tracts from 17 Primary Megaureter (PM)
      affected children, referred to surgery. Comparative observations were also
      carried out on embryonal and fetal ureteral buds of both humans and bovines. A
      reciprocal resemblance was mainly objectivized between the resected "narrowed"
      ureters of patients under 18 months, and the fetal ureteral buds at 26th and 38th
      gestational week. A development delay was irrespectively observed in PM
      "narrowed" ureters, at the longitudinal muscle-bundles in the parietal juxta
      luminal compartment. A consistent TGF-beta immunostain cytoplasmic reaction there
      selectively depicted the growing mesenchymal lines, including both the
      undifferentiated single cells and the muscle-like profiled ones. These results
      agree with very recent reports perspecting a segmental maturation delay as a
      pathogenetic moment of PM. Because of the acquired potent TGF-beta inhibitory
      role on myoblasts differentiation, the present study substantiates a persistent
      TGF-beta role in perinatal ureter dilations.

PMID- 7567643
TI  - [Lactitol in chronic idiopathic constipation in children].
AB  - Fifty-one children affected by chronic idiopathic constipation (23 males, 28
      females), ranging in age from 8 months to 16 years were enrolled in the study; 42
      completed the trial. The patients were divided into two groups: Group A: 19
      children treated with lactitol (250-400 mg/kg/day); Group B:23 patients treated
      with lactulose (500-750 mg/kg/day). Parents filled a questionnaire concerning
      clinical response to therapy for a period of 30 days. In 17 Group A children and
      in 17 Group B children orocecal transit time using H2 Breath Test with lactulose
      was performed. A statistically significant increase of week stool frequency was
      found after treatment both with lactitol or lactulose (p < 0.001). Nevertheless
      Group B patients complained abdominal pain (p < 0.005) and flatus (p < 0.001)
      more frequently. Other adverse reactions, such as vomiting and meteorism, were
      more frequent in Group B patients (n.s.). In addition patients treated with
      lactitol found that sugar as more palatable and had a better compliance to the
      therapy. Orocecal transit time did not show statistically significant differences
      after the therapy with both these sugars, indicating that the activity of
      lactulose and lactitol occurs in the colon and that small bowel functions are not
      affected by a previous therapy with these sugars. In conclusion, our study
      demonstrate that lactitol, because of the less number of side effects compared to
      lactulose, should be considered as an useful agent in the treatment of chronic
      idiopathic constipation in childhood.

PMID- 7567645
TI  - [Clinico-epidemiological considerations of 30 cases of pulmonitis and
      pleuropulmonitis in childhood].
AB  - The authors studied 30 children affected with pneumonia or pleuropneumonia. They
      point out some clinical and epidemiological features pertinent to the pathology
      examined.

PMID- 7567646
TI  - [The correlation between psittacosis-ornithosis and the immune status in
      childhood: apropos 5 cases].
AB  - The authors studied 5 children affected with a pneumopathy by Chlamydia psittaci.
      They discuss the effects of a transitory immunodeficiency relative to NK cells in
      predisposing little patients to the infective disease.

PMID- 7567644
TI  - Bone marrow transplantation in Hunter syndrome (mucopolysaccharidosis type II):
      two-year follow-up of the first Italian patient and review of the literature.
AB  - A patient with Hunter syndrome, or mucopolysaccharidosis type II (MPS-osis II),
      was subjected to bone marrow transplantation (BMT), at the age of 2 9/12 years. A
      two-year follow-up ensued to the purpose of comparing clinical, biochemical,
      neuropsychologic status pre- and post-BMT. From the clinical standpoint, a
      complete normalization of hepatosplenomegaly was observed. In addition the skin
      decreased in thickness and joint mobility improved. The echocardiography showed
      normalization of left ventricle size. With the exception of verbal capabilities,
      there was no further deterioration of the neuropsychologic profile. The
      ultrastructural examination of the liver showed an almost total disappearance of
      storage material. Normal iduronate sulfatase levels in leukocytes and
      lymphoblasts were constantly found after BMT. A qualitative and quantitative
      improvement in urinary glycosaminoglycan (GAG) excretion was also found. The
      effectiveness of the BMT in our patient is also assessed in the context of the
      few cases of MPS-osis II that have been reported to date. A final evaluation of
      the efficacy of BMT in MPS-osis II will be possible only when a higher number of
      patients, diagnosed as early as possible and transplanted within the first months
      of life, can be followed-up for more extended periods of time.

PMID- 7567648
TI  - [Fractures of the temporomandibular joints in childhood from indirect trauma to
      the chin. A report of 4 cases].
AB  - We observed four cases of temporomandibular joint fractures in children; all from
      indirect chin traumas. Traditional X-ray is not enough for a correct radiological
      diagnosis. CT, in particular with the axial scans, electronics coronal
      reconstructions, and where is possible direct sagittal scans, is able to give us
      a correct diagnosis about the nature and the site of the fractures.

PMID- 7567647
TI  - [Abdominal-scrotal hydrocele: a report of 4 cases and a review of the
      literature].
AB  - The authors report on four cases of abdomino-scrotal hydroceles treated in the
      last 5 years. They review the literature that produces 29 cases in the pediatric
      age and they examine the etiopathogenesis, the diagnosis and the therapy. The
      clinical examination and the ultrasound are without any doubt the easier, not
      invasive and more adequate surveys for the diagnosis. Surgery is the treatment of
      choice: hydrocelectomy by inguinal approach.

PMID- 7567649
TI  - Use of fiberoptic bronchoscopy in asthmatic children with lung collapse.
AB  - Segmental atelectasis during asthmatic attacks as a consequence of bronchospasm
      and hypersecretion are very frequent in children. The collapse of a lung instead
      is a very rare occurrence. We report two patients with acute exacerbation of
      asthma, showing an in complete response to bronchodilatory therapy. The clinical
      findings and chest X-ray were suggestive for collapse of a lung. An urgent
      fiberoptic bronchoscopy revealed obstruction of a stem main bronchus caused by
      sticky mucopurulent secretions. The aspiration improved dramatically the
      respiratory distress and the radiological picture. In these cases we recommended
      to perform an immediate bronchial aspiration by means of a flexible instrument
      without waiting a further deterioration of respiratory function before taking
      this decision.

PMID- 7567651
TI  - [The superior thoracic outlet compression syndrome: a report of a case in
      childhood with complete cervical rib].
AB  - Authors report a paediatric patient with thoracic outlet syndrome (TOC) and
      complete cervical rib. The symptoms at the time of presentation result from
      pressure on either the subclavian vessels or the lower trunk of the brachial
      plexus. TOC is infrequent in young people and usually the symptomatology does'nt
      need a surgical approach. Some Authors affirm that there are necessary impulsive
      moments like growth, increased muscular mass and rib ossification, decreased
      elasticity of ligaments, vessels, muscles and nerves, for outcoming the clinical
      manifestations. Paediatric competention has risen until adolescent age and may be
      more frequent the observation of this syndrome that present problems of both
      diagnosis and management.

PMID- 7567653
TI  - [The effects of growth hormone in children with a GH deficiency: a report of 5
      cases].
AB  - The authors describe 5 cases, 3 boys and 2 girls, with idiopathic growth hormone
      deficiency in prepubertal age, treated with human growth hormone. In four of five
      cases the response to treatment with GH was relevant. Only in one case (F1) the
      response was negative. The results of this study confirm that rhGH is a safe and
      effective therapy in children with GHD.

PMID- 7567652
TI  - [Deep venous thrombosis and the prevention of a pulmonary embolism with temporary
      caval filters: the experience in 2 pediatric cases].
AB  - Deep venous thrombosis with pulmonary embolism is considered rare in pediatric
      population, but a literature review points out this disease more frequent than
      would be expected in children. The low incidence and the poor consideration of
      this occurrence in pediatric age group, cause the thromboembolic disease with
      pulmonary involvement an often missed diagnosis. The illness is usually related
      to intravenous catheters, surgery, trauma, sepsis, prolonged immobilization,
      neoplasia, drugs, some congenital or acquired diseases. The Authors report their
      experience with two pediatric cases of inferior vena cava thrombosis and
      pulmonary embolism treated with anticoagulant therapy, temporary vena cava
      filters and locoregional fibrinolysis.

PMID- 7567654
TI  - [Urokinase in a premature infant: its use in a case of right atrial thrombosis
      secondary to catheterization of the umbilical vein].
AB  - Newborns with vascular catheters must be investigated by echocardiogram for
      intracardiac thrombosis. We report the use of urokinase to treat an asymptomatic
      right atrial thrombus in a 31 weeks' gestation newborn; the thrombosis occurred
      after placement of a catheter in the umbilical vein. We obtained a safe and
      successful thrombolysis using urokinase 4000 U/kg/h in continuous infusion.

PMID- 7567655
TI  - [Hydrocele in Kawasaki disease].
AB  - Although the diagnostic criteria for Kawasaki disease (KD) have been clearly
      defined, there are many reports on other signs associated with the disease.
      Kabani et al. in 1991 described three consecutive patients with combined atypical
      presentation of the disease and communicating hydrocele. To our knowledge, the
      first case of hydrocele during the course of KD was that described by us in 1990.
      Here we present an additional case of hydrocele developed at the onset of a
      typical Kawasaki disease. We think that hydrocele must be reported in the list of
      possible signs associated with Kawasaki disease and that if present, it should be
      particularly usefull for diagnosis of atypical presentation of the disease.

PMID- 7567656
TI  - [Fat necrosis in the newborn].
AB  - Subcutaneous fat necrosis is an inflammatory disorder of adipose tissue that
      occurs in the newborn. Fat necrosis has been attributed to birth trauma,
      asphyxia, prolonged hypothermia. Usually involute spontaneously within weeks to
      months. Hypercalcemia and hyperlipemia have also been associated.

PMID- 7567650
TI  - [THe echographic diagnosis of diaphragmatic eventration in newborn infants. 2
      cases].
AB  - The authors report two cases of neonatal partial diaphragmatic eventration. The
      diagnosis in both two cases was echographic more than radiographic. The authors
      underline the role of B-mode echography in the diagnosis and follow-up of
      diaphragmatic anomalies, especially eventration, and suggest that examination of
      diaphragm and of its motion should complete any abdominal and thoracic
      echography.

PMID- 7567657
TI  - [The Guillain-Barre syndrome in childhood].
AB  - The authors describe a case day Guillain-Barre syndrome admitted in pediatrics
      hospital department for asthenia. Approximately an hour after admission, the
      patient showed dysphagia and respiratory insufficiency and was diagnosed a
      Guillain-Barre syndrome, successfully treated.

PMID- 7567658
TI  - [A case of camphor poisoning].

PMID- 7567661
TI  - Risk of pulmonary tuberculosis in children with congenital heart disease.
AB  - Children with low-flow congenital heart lesions are reported to have an increased
      incidence of pulmonary tuberculosis. The aim of this study was to investigate if
      children with congenital heart disease have an increased incidence of pulmonary
      tuberculosis and to determine if patients with certain heart conditions are more
      susceptible to pulmonary tuberculosis than others. This retrospective study over
      a 6-year period showed that pulmonary tuberculosis was 2.5-fold more common in
      children with congenital heart disease than in normal children from the same
      community. Children with congenital pulmonary stenosis had a prevalence equal to
      those with acyanotic (ventricular and atrial septal defects) and cyanotic
      (transposition of the great arteries) high-flow heart lesions, whereas there were
      no cases of tuberculosis in children with low-flow cyanotic heart lesions such as
      tetralogy of Fallot. Cardiac surgery had to be postponed as a result of pulmonary
      tuberculosis in 7.2% of all patients in whom it was required. Over the 6-year
      period of the study, cardiac surgery had to be delayed in 60% of cases with
      pulmonary tuberculosis and congenital heart lesions so antituberculosis therapy
      could be completed. Physicians treating children with congenital heart lesions
      should maintain a high index of suspicion for the development of pulmonary
      tuberculosis, especially in those with acyanotic and cyanotic high-flow lesions
      and pulmonary stenosis.

PMID- 7567660
TI  - Ambulatory blood pressure in patients with occult recurrent coarctation of the
      aorta.
AB  - The hypothesis that mild recurrent aortic obstruction produces subtle changes in
      ambulatory blood pressure was investigated by performing 24-hour monitoring on 11
      postoperative coarctation patients. Patients (age 16.1 +/- 2.7 years) were
      compared with normal controls (age 15.7 +/- 2.5 years, n = 15). Surgery (end-to
      end anastomosis) was performed at 6.0 +/- 1.0 years of age. There were no
      significant differences between patients and controls in terms of baseline blood
      pressure (right arm 123/78 +/- 4/3 mmHg versus 120/75 +/- 3/2 mmHg) or right leg
      systolic pressure (125 +/- 6 mmHg versus 123 +/- 4 mmHg). Of the 11 patients 8
      had recoarctation by Doppler study (mean gradient 25.3 +/- 2.1 mmHg), 5 of 11 had
      a postexercise arm-leg pressure difference of > 30 mmHg, and 6 patients had
      aortic diameters at the site of surgery < 70% of the descending aortic diameter
      (by magnetic resonance imaging). There were no significant differences between
      the coarctation and control groups in terms of mean ambulatory systolic (125 +/-
      3 mmHg versus 119 +/- 2 mmHg) or diastolic (69 +/- 2 mmHg versus 72 +/- 2 mmHg)
      pressures throughout the day. However, coarctation patients had a larger number
      of systolic pressures that exceeded the 95th percentile (18.2 +/- 5.6% versus 6.8
      +/- 1.2%). These labile increases in systolic pressure correlated with residual
      coarctation (r = 0.642, p = 0.003). Ambulatory monitoring is a useful tool for
      detecting and monitoring subtle abnormalities of blood pressure control after
      coarctation repair.

PMID- 7567663
TI  - Acquired pulmonary stenosis: ultrasonographic diagnosis.
AB  - A 15-year-old boy presented with chest pain and a new heart murmur. The clinical
      diagnosis of pulmonary stenosis was confirmed by two-dimensional and Doppler
      echocardiographic examinations. A large, encapsulated, partly solid and partly
      cystic tumor in the anterior mediastinum, visualized by ultrasonography, was
      compressing the main pulmonary artery and producing the right ventricular outflow
      tract obstruction. The tumor was removed surgically and was found to be a benign
      teratoma. Postoperative ultrasound examination of the right ventricular outflow
      tract showed no evidence of obstruction. We conclude that: (1) there are subtle
      clinical diagnostic differences between intrinsic and extrinsic pulmonary
      stenosis; (2) ultrasound examination can make cardiac catheterization
      unnecessary; and (3) relief of the extrinsic cause of pulmonary stenosis should
      be curative.

PMID- 7567662
TI  - Left ventricular growth in a patient with critical coarctation of the aorta and
      hypoplastic left ventricle.
AB  - An infant is presented who at birth met criteria consistent with hypoplastic left
      heart syndrome. He was followed clinically and by 11 weeks of age demonstrated
      substantial growth of the left ventricle. He underwent successful repair of
      coarctation of the aorta and continues to do well with moderate aortic stenosis.
      The difficulties of predicting left ventricular growth and function are
      discussed, and management options are reviewed.

PMID- 7567664
TI  - Left ventricular thrombosis during infancy: report of two cases.
AB  - Two patients with left ventricular thrombosis diagnosed by echocardiography are
      presented. The first patient was a 6-week-old girl with supraventricular
      tachycardia. Cross-sectional echocardiography showed a rounded and mobile
      structure protruding from the left ventricular wall. The girl was in heart
      failure and had signs of peripheral embolization. After sinus rhythm had been
      restored the thrombus diminished gradually and the girl recovered. The second
      patient was a newborn boy with severe aortic stenosis and a large massive
      thrombus along the left side of the interventricular septum. The boy died after
      valvotomy, the post-mortem examination confirmed the diagnosis of a large
      thrombus. Left ventricular thrombosis is uncommon in neonates and infants but may
      appear secondary to abnormal hemodynamics.

PMID- 7567665
TI  - Successful thrombolytic therapy using tissue-type plasminogen activator in
      Kawasaki disease.
AB  - Thrombolytic therapy using tissue-type plasminogen activator was performed in a 7
      month-old boy with massive mural thrombi in large coronary aneurysms due to
      Kawasaki disease. Magnetic resonance imaging successfully demonstrated mural
      thrombi in both proximal and distal coronary aneurysms and their disappearance
      after thrombolytic therapy. We conclude that for preventing acute myocardial
      infarction and sudden death intravenous and intracoronary thrombolytic therapy
      with tissue-type plasminogen activator may help in infants and children with
      Kawasaki disease who have thrombi in coronary aneurysms.

PMID- 7567666
TI  - Rudimentary pulmonary valve and ventricular septal defect associated with patent
      ductus arteriosus.
AB  - This report describes a rare case of patency of the ductus arteriosus in the
      setting of ventricular septal defect and rudimentary pulmonary valve. We comment
      on the fetal, neonatal, and postmortem findings and speculate about the role of
      the ductus arteriosus in the development of dilatation of the pulmonary arteries
      in this malformation.

PMID- 7567659
TI  - Incidence of congenital heart disease: II. Prenatal incidence.
AB  - The incidence of congenital heart disease appears to be about 1 per 100 liveborn
      infants. In infants who die before term, however, there is a much higher
      incidence of congenital heart disease, with a tendency for an excess of complex
      lesions. Some but not all of these lesions are associated with gross chromosomal
      abnormalities, which occur frequently in first-trimester abortions. Most of these
      chromosomal abnormalities are associated with such maldevelopment of many organ
      systems that fetal death occurs in utero. Monosomy X (45, XO), has a high
      association with congenital heart disease. Most fetuses with this abnormality die
      in utero, but because the abnormality is not inevitably lethal a small increase
      in survival of these fetuses would cause a large increase in the total incidence
      of congenital heart disease.

PMID- 7567668
TI  - Unexpected oxygen desaturation after cardiopulmonary bypass: rapid confirmation
      of unroofing of the coronary sinus by intraoperative epicardial echocardiography.
AB  - Unexpected arterial oxygen desaturation occurred immediately after
      cardiopulmonary bypass in two children. Epicardial echocardiography demonstrated
      unroofing of the coronary sinus after a Fontan procedure in the first child and
      rapidly excluded this abnormality in the second, who had undergone closure of a
      sinus venosus defect and in whom there was also a left superior vena cava
      draining to the coronary sinus. Epicardial echocardiography determined management
      in both patients: Oversewing of the ostium of the coronary sinus was undertaken
      in the first case during an additional period of cardiopulmonary bypass. Oxygen
      saturation values improved with aggressive endotracheal lavage and aspiration of
      secretions in the second child. Epicardial echocardiography can identify
      unroofing of the coronary sinus (which may be difficult to diagnose by
      transesophageal echocardiography) and can identify or exclude this condition when
      unexpected arterial oxygen desaturation is present after cardiac surgery.

PMID- 7567667
TI  - Persistent hemolysis after transcatheter occlusion of a patent ductus arteriosus:
      surgical ligation of the duct over the occlusion device.
AB  - A 14-month-old child underwent routine transcatheter closure of her patent ductus
      arteriosus (PDA) using the Rashkind double-umbrella device. She developed severe
      persistent hemolysis in association with residual ductal flow. The problem was
      managed by the previously unreported approach of standard surgical ligation of
      the duct via a left thoracotomy, leaving the occlusion device in situ.

PMID- 7567669
TI  - Modified Fontan procedure for left atrial isomerism: alternative technique.
AB  - Anomalous systemic or pulmonary venous connections increase the risk and
      technical difficulty of the modified Fontan procedure. This report describes an
      alternative technique of total diversion of systemic venous return to the
      pulmonary artery in a child with left atrial isomerism, incorporating an
      extracardiac conduit between the hepatic veins and the right pulmonary artery.

PMID- 7567671
TI  - Intussusception of catheter sheath.

PMID- 7567672
TI  - Functional analysis in behavior therapy.

PMID- 7567674
TI  - Cognitive behavioral strategies in athletic performance enhancement.
AB  - While we might debate the role of sport in our culture, its influence is
      certainly pervasive. Each day millions of Americans engage in some form of
      competition, training, or physical exercise. Such popularity and the value our
      culture places on competition have made sport a valid area of psychological
      inquiry. Within the cognitive behavioral model, sport psychology and,
      specifically, athletic performance enhancement have experienced vigorous growth
      over the past two decades. Behavior change strategies familiar to most cognitive
      behaviorists form the core of virtually all athletic performance enhancement
      interventions. Goal setting, imagery or mental rehearsal, relaxation training,
      stress management, self-monitoring, self-instruction, cognitive restructuring,
      and modeling interventions dominate this literature. Our examination of these
      performance enhancement programs, both through a qualitative review and the
      Whelan et al. (1989) meta-analysis, supports the efficacy of cognitive behavioral
      interventions for the enhancement of sport performance. First, the average effect
      size across the empirical literature indicates that these interventions are
      reliably effective. Furthermore, this positive result is observed across
      variations in treatment conditions, control conditions, and across different
      types of dependent measures. Evidence on goal setting, imagery, arousal
      management, cognitive self-regulation, and packaged programs specifically support
      the behavior change efficacy of these interventions. These findings are
      encouraging, but much work needs to be done. Few investigators cited in this
      review attend to crucial internal and external validity issues. Attention to
      treatment integrity, including training of behavior change agents, verification
      of intervention implementation, and verification of reception of the treatment,
      is sorely lacking. Psychological skill development and its relationship to
      performance improvements are rarely checked. Now that cognitive behavioral
      interventions appear to be reliably effective at posttreatment, we must have
      meaningful evaluation of maintenance of psychological skill and performance
      changes. Six-month, 12-month, and longer follow-up evaluations are necessary. We
      must also begin more detailed evaluations of these effective
      interventions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7567673
TI  - Behavior therapy with lesbian and gay individuals.

PMID- 7567670
TI  - Heart transplantation in an infant with rhabdomyoma.
AB  - Rhabdomyoma is the most common primary cardiac tumor in infants and children and
      is often associated with tuberous sclerosis. Surgical resection may be indicated
      and, if so, is usually curative. We describe a rhabdomyoma in an infant who
      presented with severe myocardial ischemia necessitating orthotopic heart
      transplantation.

PMID- 7567675
TI  - Posttraumatic stress disorder: conceptualization and treatment.
AB  - After a long history of both scientific and political debate, the notion that
      extreme psychological traumatic experiences, in and of themselves, could result
      in a severe, even malignant, psychiatric disorder is now established. In 1980
      posttraumatic stress disorder finally became an officially classified anxiety
      disorder. Since then, the few controlled treatment outcome studies that have been
      carried out appear to indicate that the most effective treatment for PTSD is some
      form of exposure therapy. This is not surprising in light of the fact that
      several other types of anxiety disorders respond well to this form of behavioral
      treatment. However, PTSD may be more complex than the other types of anxiety
      disorders, especially with regard to the variety of symptoms involved. In its
      chronic form or in combat-related PTSD, no one type of treatment tested so far
      has been successful in reducing all the symptoms of the disorder.
      Psychophysiological overarousal to imaginal facsimiles of the traumatic event is
      especially difficult to influence with treatment. Identifying techniques that
      reduce or at least control this arousal will likely be grist for the research
      mill for many years. Theoretical and conceptual formulations regarding both the
      etiology and treatment of the disorder are in early stages of development. It is
      hoped that these efforts will eventually mature our understanding of the disorder
      as researchers explore important issues such as (1) predisposing factors; (2) how
      the nature and intensity of the stressor relates to the severity of the disorder;
      and (3) how biological, psychological, social, and cultural variables interact to
      result in PTSD and to either ameliorate or exacerbate its symptoms.

PMID- 7567676
TI  - Psychosocial interventions for adolescent depression: issues, evidence, and
      future directions.

PMID- 7567678
TI  - Behavioral treatment of depression in the context of marital discord.

PMID- 7567677
TI  - Social phobia: diagnostic issues and review of cognitive behavioral treatment
      strategies.

PMID- 7567679
TI  - Central neurocytoma. A clinicopathological, immunohistochemical and
      ultrastructural study of 7 cases.
AB  - Characterised by distinctive clinicopathological features, the central
      neurocytoma (CN) is an uncommon and possibly under-recognised primary cerebral
      neuronal neoplasm. We present clinical and pathological details of seven patients
      with CN. Histological examination revealed a greater diversity of morphological
      appearances than is typically described in CN. No anaplastic features were
      identified. Cellular areas resembling both oligodendroglioma and ependymoma were
      present in all cases, but each tumour also contained stroma rich areas with
      hyalinised or aneurysmal vessels. Synaptophysin was expressed by all tumours and
      probably represents the immunohistochemical marker of choice for identifying CN.
      Distinguishing ultrastructural features included rounded cell bodies separated by
      numerous cell processes containing microtubules, pleomorphic neurosecretory
      granules and occasional synapses. Ki-67 immunostaining revealed a low cell
      proliferation index in each case. The distinction of CN from other pathological
      mimics can be reliably made using this multiparametric approach to diagnosis. The
      generally benign behaviour of CN is confirmed, though there was one patient death
      in the follow-up period of 10-122 months. Aggressive behaviour in this case was
      not associated with anaplastic histological features.

PMID- 7567680
TI  - Adamantinoma of long bones. A histopathological and immunohistochemical study of
      23 cases.
AB  - The clinical and histological data of twenty-three cases of adamantinomas of the
      long bone collected by the Working Group on Bone Tumors at the DKFZ/FRG are
      reported including immunohistochemical observations in twenty-one of the cases.
      Females and males between 5 and 67 years (mean, 25.4 years) were affected equally
      (11/12). All adamantinomas were positive for cytokeratins often in coexpression
      with vimentin, at least focally. Although exhibiting varying histological
      patterns, no correlation between histology and clinical course was seen. However,
      sex and mode of initial therapy seem to influence an unfavorable clinical
      outcome. All three decreased patients were males receiving marginal or delayed
      surgery. This underlines the low-grade malignant character of adamantinoma. To
      assure the histological diagnosis pathologists should employ immunohistochemistry
      for demonstrating the sometimes sparse epithelial cell nests when radiology is
      suggestive for adamantinoma. Correct diagnosis should lead to resection with wide
      surgical margins.

PMID- 7567681
TI  - Histochemistry and immunohistochemistry on bone marrow biopsies. A rapid
      procedure for methyl methacrylate embedding.
AB  - Starting from previous methodical approaches a procedure for low temperature
      methyl methacrylate (MMA) embedding of bone marrow biopsies is introduced, which
      allows routine application of enzyme and immunohistochemistry without loss of
      morphological quality by retaining fixation in Schaffer's solution. Survival of
      enzyme activity and antigen determinants is achieved by washing the fixed
      specimens in 70% methanol and dehydration in acetone in ascending concentrations
      at 4 degrees C. Modifications of the plastic embedding technique used in this
      study simplify and shorten the procedure, so that embedding according to this
      routine method is complete after two days of preparation. Additionally, a rapid
      embedding variant is introduced, which enables tissue preparation within one day
      if necessary. Results are demonstrated using markers for myeloid, lymphoid and
      epithelial cells as well as immunoglobulins and the proliferation associated
      antigen Ki-67. The investigation of a panel of monoclonal and polyspecific
      antibodies in 31 cases shows the eventually reduced immunoreactivity of a few
      markers after prolonged fixation. As a consequence it seems essential to ensure
      short fixation periods, especially when the specimens are sent by mail.

PMID- 7567682
TI  - Involvement of the larynx by hemopoietic neoplasms. An investigation of autopsy
      cases and review of the literature.
AB  - Involvement of the larynx by hemopoietic tumors is generally considered a rare
      event and little is known about the associated clinicopathologic features.
      Laryngeal tissue removed at autopsy from 14 patients with known disseminated
      hematologic malignancies and at operation from one patient with multicentric
      malignant lymphoma of low-grade malignancy (MALToma) of the head and neck region
      was investigated. A systematic survey of the main clinicopathologic features of
      the published cases of hemopoietic tumors with laryngeal involvement was also
      performed. Primary involvement of the larynx by hemopoietic neoplasms must be
      clearly distinguished from secondary involvement by disseminated or leukemic
      tumors. Most of the primary tumors are localized lesions that may involve the
      regional lymph nodes (stages IE or IIE). Radiotherapy is the treatment of choice,
      and the prognosis is generally favorable. However, secondary involvement by
      disseminated or leukemic disease carries a very poor prognosis in most cases.
      Extramedullary plasmacytoma and non-Hodgkin's lymphoma (NHL), particularly B-cell
      lymphoma of high-grade malignancy, appear to be the most common hemopoietic
      tumors with primary laryngeal involvement, while primary tumors of myelogenous
      origin (granulocytic sarcoma and mast cell sarcoma) are extremely rare.
      Extramedullary plasmacytoma and NHL occur mainly in older persons and in men, are
      generally associated with a relatively short history of hoarseness and dysphagia,
      and exhibit preferential involvement of the supraglottic parts of the larynx, in
      particular the epiglottis and aryepiglottic folds. They are generally polypoid,
      non-ulcerated lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567683
TI  - Demonstration of Epstein-Barr virus genomes, using polymerase chain reaction in
      situ hybridization in paraffin-embedded lymphoid tissues.
AB  - We used the polymerase chain reaction (PCR) in situ hybridization (ISH) (PCR-ISH)
      on sections of malignant lymphoma and nonspecific lymphadenitis to detect small
      amounts of Epstein-Barr virus (EBV), a DNA virus of the herpes virus family. We
      first surveyed the EBV DNA by Southern blot analysis and PCR, and then compared
      results of the two PCR/ISH methodologies with the results of simplified/sensitive
      ISH for the positive cases. The target of the simplified in situ (DNA-ISH) was a
      few copies of EBV DNA per cell, and the target of the sensitive in situ (RNA-ISH)
      was as many as 10(7) copies of EBV RNA per cell. When EBV DNA was detected by
      Southern blot, DNA-ISH, RNA-ISH and PCR-ISH all revealed EBV genomes. When PCR
      revealed only amplified EBV DNA, DNA-ISH showed no EBV genomes, but PCR-ISH and
      RNA-ISH showed EBV genomes in a few cells. When PCR showed no detectable
      amplified EBV DNA, all of DNA-ISH, RNA-ISH and PCR-ISH showed no genomes. These
      findings indicate that PCR-ISH consistently detected a few copies of the EBV
      virions. The PCR-ISH was as sensitive as RNA-ISH. The RNA-ISH could not detect
      virus if RNA was not expressed, but the PCR-ISH could detect virus without such
      expression. The ability to detect a single copy of a specific gene in situ has
      many advantages and multiple applications in molecular biology, pathology, and
      cell biology.

PMID- 7567684
TI  - Limited TCR V beta usage of infiltrating T cells in synovial tissues from
      patients with HTLV-I associated arthropathy.
AB  - Human T cell lymphotropic virus type-I (HTLV-I) is the etiologic agent of adult T
      cell leukemia/lymphoma and recently has also been suggested to be involved in
      chronic arthritis. The synovia of patients with rheumatoid arthritis (RA)
      contains activated T lymphocytes, with a restricted expression of T cell receptor
      (TCR) variable (V) beta gene segments. To characterize the T-cell populations of
      RA among HTLV-I carriers and noncarriers, we performed the immunohistochemical
      staining of CD4 and CDB, as well as a reverse transcription polymerase chain
      reaction (RT-PCR) to estimate the proportion of TCR beta RNA containing any
      particular V elements on the synovial specimens. In all but one HTLV-I carrier,
      the proviral DNA and/or RNA expression of HTLV-I was detected in the synovium.
      The CD4-positive cells proliferated markedly in the HTLV-I carriers compared with
      the noncarriers. In contrast to mononuclear cells in the peripheral blood,
      synovial T cells expressed only a few V beta transcripts, and no definite
      difference was observed between the carriers and the noncarriers. These results
      suggest that a common major antigen associated with the pathogenesis of RA may
      thus selectively interact with the V beta component of the TCR. Using RT-PCR, we
      studied the expression of the recombination-activating gene-1 (RAG-1), which was
      used in the V(D)J recombination of immunoglobulin and TCR genes. In all cases,
      RAG-1 was transcripted. The results supported the possibility that the
      extrathymic development of the selected TCR V beta T cells occurred in the
      synovia.

PMID- 7567685
TI  - Gynecomastia with unusual intraductal "clear cell" changes mimicking pagetoid
      ductal spread of lobular neoplasia.
AB  - This report describes a case of unusual intraductal "clear cell" changes of male
      breast that mimicked pagetoid ductal spread of lobular neoplasia. The lesion
      developed inside a nodule of gynecomastia of the left breast in a 56 year-old
      man. Immunohistochemically, the enlarged clear cells reacted positively with
      epithelial membrane antigen, low molecular weight cytokeratin and three breast
      markers (i.e.: gross cystic disease fluid protein-15 and -44 and estrogen
      receptors). They were negative for high molecular weight cytokeratin, muscle
      specific actin, desmin and vimentin. Differential diagnoses included pagetoid
      ductal involvement by lobular neoplasia (i.e.: lobular carcinoma in situ and/or
      atypical lobular hyperplasia), pagetoid growth of intraductal carcinoma, atypical
      intraductal hyperplasia, and unusual intraductal myoepithelial proliferative
      lesion.

PMID- 7567686
TI  - Sinonasal teratocarcinosarcoma: an unusual neoplasm.
AB  - Sinonasal teratocarcinosarcoma (SNTCS) is a very unusual and aggressive neoplasm
      characterized by the combination of malignant teratoma and carcinosarcoma
      features, of which less than forty cases have been reported in the literature. We
      report on a 75-year-old man with SNTCS that involved the left ethmoid, maxillary
      and sphenoidal sinuses. The tumor showed a complex histological pattern with
      mature and immature glands, benign squamous and malignant poorly differentiated
      epithelia, as well as neuroblastoma-like tissue and sarcoma component with
      rhabdomyoblastic differentiation. This peculiar blend of tissue types makes the
      diagnosis of this entity a difficult challenge, especially in small biopsies or
      in tumors only partially removed. This tumor must be differentiated from several
      types of carcinomas, esthesioneuroblastoma, craniopharyngioma, malignant mixed
      tumor of salivary gland type and germ cell tumors. The present case represents,
      to our knowledge, the third SNTCS described in the european literature.

PMID- 7567688
TI  - Evaluation of Ki-67 reactivity in neuroblastoma using paraffin embedded tissue.
AB  - AIMS: To examine the pattern of reactivity of Ki-67 in neuroblastoma and
      correlate this with a) clinical prognostic criteria and b) cell cycle statistics
      (using flow cytometry). METHODS: Four micron sections of paraffin embedded (PE)
      tissue from 55 patients (25 pre chemotherapy and 30 post) were placed on to
      aminosialinised slides, dewaxed and rehydrated. Slides were pretreated in a
      microwave oven, endogenous peroxidase activity blocked using 3% hydrogen peroxide
      and Ki-67 reactivity investigated using a streptavidin/biotin/peroxidase
      technique. DNA ploidy was also performed from an immediately adjacent section on
      the same block using a FACScan and Cellfit software. RESULTS: Ki-67 reactivity
      was well defined and highly reproducible. Eighteen out of 30 post chemotherapy
      samples were totally negative, despite evidence of proliferation on flow
      cytometry and all subsequently died of disease. As interpretation post
      chemotherapy was therefore deemed unreliable, this group was excluded from
      analysis. Reactivity in pretreatment samples ranged from 0% to 67%; staining was
      restricted to the nucleus with a distinct pattern noted in the nucleolus. Ki-67
      positivity was lower in aneuploid compared with diploid tumours (mean 26% vs 36%,
      NS). Among diploid tumours, a lower percentage positivity was noted in those
      patients with better clinical prognostic parameters. Correlation however between
      Ki-67 and SG2M phases of cell cycle was poor (RS = 0.39, NS). CONCLUSION:
      Assessment of proliferation in neuroblastoma by Ki-67 reactivity in paraffin
      embedded tissue is reliable in pretreatment samples and can be incorporated into
      routine immunohistochemical evaluation. Larger multicentre studies are required
      to further evaluate Ki-67 reactivity as a prognostic indicator.

PMID- 7567687
TI  - Soft tissue chondroma of the fallopian tube. Differential diagnosis and
      histogenetic considerations.

PMID- 7567689
TI  - Ret-oncogene expression correlates with neuronal differentiation of neuroblastic
      tumors.
AB  - An antibody to the ret proto-oncogene product (RET) was raised and applied to
      formalin-fixed, paraffin-embedded neuroblastic tumors (NBTs) to investigate its
      usefulness in diagnosis and evaluation of cell differentiation. In normal neural
      crest-derived tissues, most ganglion cells were moderately stained while large
      ganglion cells were weakly stained. In NBTs, the intensity of the staining in
      moderately differentiated neuroblasts and small ganglion cells was more prominent
      than in undifferentiated neuroblasts, while the cytoplasm of large ganglionic
      cells was weakly stained as in normal ganglion cells. The RET immunoreactivity
      was compared with that of nine neural and neuroendocrine markers. The results
      revealed a parallelism with the protein gene product 9.5 (PGP9.5), neuron
      specific enolase (NSE) and NF-150 kD (NF = M). These findings indicated that the
      RET immunoreactivity was correlated with ganglionic differentiation and
      maturation. Thus, RET was considered to be a new marker that would be implemented
      in diagnosis and estimation of neuronal differentiation of NBTs.

PMID- 7567693
TI  - Orthotopic placement of the Dunning R3327 AT-3 prostate tumor in the Copenhagen X
      Fischer rat.
AB  - Orthotopic placement of in vitro propagated Dunning R3327 AT-3 tumor cells
      resulted in a greater percentage of tumor takes and a two-fold shift in the
      exponential growth curve compared to flank implantation. The orthotopic tumor
      appeared to disseminate preferentially to regional lymph nodes, rather than to
      the lungs which is characteristic of flank tumors. The results suggest an
      important role of stromal-epithelial interactions in the growth of this tumor.

PMID- 7567690
TI  - Quantitative evaluation of glandular and stromal compartments in hyperplastic dog
      prostates: effect of 5-alpha reductase inhibitors.
AB  - The objective of this study was to determine the effects of 2 different 5-alpha
      reductase inhibitors (finasteride and MK-0434) on the glandular and stromal
      compartments of hyperplastic canine prostates. In this study, dogs received 1 of
      the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs
      received a placebo. The morphological changes in the glandular and stromal
      compartments in the prostate were quantitated by a point-counting method on
      Masson's trichrome-stained sections. Treatment with 5-alpha reductase inhibitors
      resulted in significant (P < or = 0.05) decreases in mean prostatic volumes,
      microscopic evidence of prostatic atrophy, and significant (P < or = 0.05)
      decreases in the absolute volumes of the prostatic glandular and stromal
      compartments compared to controls. In finasteride-treated dogs, the mean percent
      change from baseline was: epithelium, -52; lumens, -58; fibrovascular stroma, 
      41; and smooth muscle, -29. In MK-0434-treated dogs, the mean percent change from
      baseline was: epithelium, -77; lumens, -58; fibrovascular stroma, -38; and smooth
      muscle, -42. The effect on the glandular compartment in dogs treated with MK-0434
      was slightly greater than in dogs treated with finasteride; however, the effect
      on the stroma was similar. These results clearly demonstrate that inhibition of 5
      alpha reductase enzyme activity affects growth and maintenance of both glandular
      and stromal compartments of dog hyperplastic prostates. It is likely that the
      decrease in size of the prostate in finasteride-treated (Proscar) men is due to
      shrinkage of both glandular and stromal compartments.

PMID- 7567691
TI  - Liarozole, an antitumor drug, modulates cytokeratin expression in the Dunning AT
      6sq prostatic carcinoma through in situ accumulation of all-trans-retinoic acid.
AB  - Liarozole showed antitumoral activity in the Dunning AT-6sq, an androgen
      independent rat prostate carcinoma. To investigate its potential mechanism of
      action, the effects of the drug doses (ranging from 3.75 to 80 mg/kg b.i.d.) on
      endogenous plasma and tissue all-trans-retinoic acid levels and on the
      differentiation status of the tumor cells were evaluated. To follow modulation of
      differentiation, cytokeratins were localized in the (un)treated tumors by
      immunocytochemistry and quantitatively determined by immunoblotting. Results
      showed that liarozole statistically significantly reduced tumor weight from 30
      mg/kg upwards and induced accumulation of all-trans-retinoic acid both in plasma
      and tumors. In the tumors, a statistically significant accumulation was already
      noted from 7.5 mg liarozole/kg upwards. Concomitantly, the differentiation status
      shifted from a keratinizing towards a non-keratinizing squamous carcinoma, which
      was further confirmed by the cytokeratin profile of the carcinoma (presence of CK
      8, 10, 13, 14, 18, 19). Immunoblotting revealed an overall decrease in
      cytokeratin content, except for CK 8. These findings suggest that the antitumoral
      properties of liarozole might be related to an increase in the degree of tumor
      differentiation through accumulation of all-trans-retinoic acid.

PMID- 7567692
TI  - Demonstration of fibroblast growth factor receptor-I in human prostate by
      polymerase chain reaction and immunohistochemistry.
AB  - The expression and localization of fibroblast growth factor receptor-1 were
      investigated in human prostatic tissues with or without benign hyperplasia. Using
      a polymerase chain reaction method, we were able to demonstrate that prostatic
      tissues with benign hyperplasia expressed a significantly higher level of
      fibroblast growth factor receptor-1 mRNA than normal prostatic tissues (P < 0.01
      by Anova). Western blot analysis using an antiserum against the receptor gave 2
      bands with molecular weights of about 140 kDa and 80 kDa; these correspond to the
      expected sizes of the long and secreted forms of the fibroblast growth factor
      receptor-1, respectively. An immunohistochemical study using the same antiserum
      further demonstrated that the immunoreactive staining occurred mainly in the
      basal cells of the glandular epithelium and occasionally in the stromal cells.
      These results suggest that fibroblast growth factors may influence, at least in
      part, the proliferation of the epithelial cells seen in benign hyperplasia of
      human prostate.

PMID- 7567695
TI  - Binding of estradiol to whole prostatic DU-145 cells in the presence and absence
      of tamoxifen and acetylsalicylic acid.
AB  - Conflicting results have been obtained with regard to the estradiol receptor (ER)
      capacity of human prostatic tissue. Human prostatic DU-145 cells have been found
      to be ER-negative with immunohistochemical assays. The object of this
      investigation was to determine if whole DU-145 cells, which had been grown in
      monolayer culture, have ER and, if so, to confirm the finding with antiestrogens.
      After cells had been lysed, a Bmax of 44.7 +/- 4.0 fmol/mg (Kd = 0.6 +/- 0.6 nM)
      was obtained. Subcellular localization studies showed that the estrogen receptor
      level in the cytoplasmic fraction was approximately 10 times higher than in the
      nuclear fraction. Competitive binding studies showed that tamoxifen, DES, and
      acetylsalicylic acid decreased estradiol binding. The dissociation constants and
      relative affinities for tamoxifen, DES, and acetylsalicylic acid were 0.2 nM
      (281.7%), 0.2 nM (224.0%), and 0.8 nM (78.43%), respectively. However, 5 alpha
      dihydrotestosterone and metabolites of acetylsalicylic acid had no effect in
      competitive binding studies. These results may contribute to a better
      understanding of prostatic carcinogenesis, which may in turn lead to more
      effective treatment.

PMID- 7567694
TI  - Determination of Ki-67 defined growth fraction by monoclonal antibody MIB-1 in
      formalin-fixed, paraffin-embedded prostatic cancer tissues.
AB  - The applicability of MIB-1, a monoclonal antibody directed against the Ki-67
      antigen, was studied in the PC-82 and LNCaP prostatic tumor models at various
      levels of proliferative activity. Statistically significant correlations were
      found in LNCaP cultures between Ki-67 and MIB-1 scores (r = 0.84, P < 0.001), and
      in PC-82 tumors between MIB-1 scores and paraffin tissue Ki-67 (pKi-67) (r =
      0.90, P < 0.001), frozen tissue (fKi-67) (r = 0.86, P < 0.001), and BrdU uptake
      (r = 0.70, P < 0.001), respectively. pKi-67 scores were double the fKi-67 scores,
      which may be due to methodological differences. MIB-1 scores exceeded both the
      fKi-67 and pKi-67 scores. The affinity of MIB-1 for the antigen is much higher
      than the affinity of Ki-67, which may explain the differences. MIB-1 is a
      promising means of evaluating the presence of only minute amounts of the Ki-67
      antigen in paraffin-embedded human tumor material, especially in relatively
      slowly growing tumors.

PMID- 7567696
TI  - In vivo and in vitro complex formation of prostate specific antigen with alpha 1
      anti-chymotrypsin.
AB  - Complex formation of prostate specific antigen (PSA) with its inhibitor alpha 1
      anti-chymotrypsin (ACT) in vivo and in vitro was studied. Patients with benign
      prostatic hyperplasia (BPH) were treated with the computer assisted device
      "Prostatron." This instrument acts by means of thermal destruction of prostatic
      tissue. The effect of the treatment was followed by measurement of serum PSA
      concentrations using commercially available immunoassays from Roche (Cobas Core),
      Wallac (Delfia) and Abbot (IMx) and Hybritech Tandem. Serum samples were further
      analyzed by molecular sieving on S.300 (Pharmacia) and analyzed for PSA by immuno
      assay. The complex formation of PSA with ACT in serum was studied, demonstrating
      this process to be influenced by external stimulus. Patient sera revealing
      initially normal PSA levels (3 to 5 ng/ml) were stimulated to very high levels of
      PSA (> or = 140 ng/ml) by Prostatron treatment. The absolute PSA level depends on
      the assay system and not only on the staging of the prostate tumor. In addition,
      complex formation was studied in athymic nude mice and in vitro revealing the
      possible pathways of PSA release. PSA from LNCAP cells kept in vitro show
      predominantly uncomplexed (free) PSA, whereas PSA from LNCAP cells injected into
      nude mice appears in the serum of the animals in complexed form. This
      demonstrates how in the immunization process free and complexed PSA serve as
      antigens in the standard procedure for the production of antisera for PSA. This
      model system also can be used for studies of the release mechanism of PSA into
      blood circulation.

PMID- 7567697
TI  - Control of infections in schools.

PMID- 7567699
TI  - Developmental dislocation of the hip: a clinical overview.

PMID- 7567700
TI  - Fluid management of children who have diabetic ketoacidosis.

PMID- 7567698
TI  - Hemophilia: an updated review.

PMID- 7567701
TI  - Divorce: consequences for children.

PMID- 7567702
TI  - Quality improvement: an ACQIP exercise on the management of acute asthma--Part 2.

PMID- 7567703
TI  - Stabilization of the very-low-birthweight infant.

PMID- 7567704
TI  - Documentation of migraine: the pattern is in the history.

PMID- 7567705
TI  - The man who has two watches: dealing with discrepancies in clinical guidelines.

PMID- 7567706
TI  - Children who have difficulty in school: a primary pediatrician's approach.

PMID- 7567707
TI  - Behavioral side effects of medications used to treat asthma and allergic
      rhinitis.

PMID- 7567708
TI  - Developmental testing.
AB  - Pediatricians play a central role in monitoring the development of infants and
      children during the course of providing well child care. Parents turn to
      pediatricians for help in determining whether their child has a temporary lag in
      development, a serious delay or disorder, or a significant behavior problem that
      should be addressed. With the passage of PL 99-457, pediatricians also play a key
      role in referring children at risk to early intervention services. By employing a
      strategy of developmental surveillance, with periodic developmental screening,
      the pediatrician can determine when a child should be referred for more extensive
      developmental or psychological testing, which will aid in the process of
      diagnosis and treatment of developmental disabilities and behavioral
      disturbances. Knowledge of the screening and testing measures used commonly, as
      well as their limitations, will result in more accurate interpretation of the
      data derived from such measures. Once delays are diagnosed and treatment is
      initiated, repeated assessments over time will serve to identify areas in need of
      continuing intervention while indicating gains made in specific areas of
      developmental functioning. Throughout this process, the pediatrician's role as
      advocate for the child and family serves as a bridge to other professionals and
      services, with the ultimate goal of facilitating the optimal development of the
      child.

PMID- 7567709
TI  - Shock.

PMID- 7567710
TI  - Index of suspicion. Case 1. Hypertrophic cardiomyopathy.

PMID- 7567711
TI  - Index of suspicion. Case 2. Aplastic anemia (Fanconi anemia).

PMID- 7567715
TI  - Consultation is a two-way street.

PMID- 7567712
TI  - Index of suspicion. Case 3. Mumps parotitis.

PMID- 7567714
TI  - Vaccination update. Diphtheria, tetanus, pertussis, mumps, rubella, measles.
AB  - Despite the availability of many effective vaccines, some vaccine-preventable
      diseases still cause significant morbidity and mortality. Increased prevention
      should be attainable through proper education about the efficacy and safety of
      vaccines, improved immunization rates, and adherence to recommended vaccination
      guidelines from the Advisory Committee on Immunization Practices. Childhood
      immunization should include a complete diphtheria, tetanus, and pertussis series
      and a measles, mumps, and rubella series. Booster doses for tetanus should be
      given every 10 years throughout life.

PMID- 7567713
TI  - Hypercholesterolemia. Dietary advice for patients regarding meat.
AB  - The contribution of beef, pork, lamb, and veal to total fat, saturated fat, and
      cholesterol intake must be evaluated from a total-diet standpoint. The hidden
      fats in snack foods and other processed foods contribute significantly to total
      fat and cholesterol intake. Patients with hypercholesterolemia can include a
      moderate amount of meat in their cholesterol-lowering diet provided they choose
      lean cuts of meat, trim visible fat, pay attention to portion size, and use low
      fat cooking methods. Substituting skinless chicken or fish for meat may make
      sense from the standpoint of personal preference and dietary variety but does not
      confer additional benefits in terms of reducing blood cholesterol levels.

PMID- 7567716
TI  - Chronic testicular pain. A workup and treatment guide for the primary care
      physician.
AB  - Chronic pain syndromes are encountered in every medical practice, and workup can
      be costly and frustrating. Patients with chronic testicular pain were once
      referred early to urologists but are now being seen and successfully treated in
      primary care offices. Referral is usually reserved for diagnosis of questionable
      testicular masses and for surgery. Antibiotic therapy, often combined with a
      nonsteroidal anti-inflammatory drug, may be useful--in some cases even when
      infection has not been identified. Spermatic cord block and transcutaneous
      electrical nerve stimulation may help relieve pain, although it often recurs.
      Antidepressants sometimes relieve pain and alleviate the psychogenic symptoms
      that may accompany it. Many patients benefit from a program at a
      multidisciplinary pain-management clinic and should complete one before opiate
      therapy is prescribed. When all conservative efforts have failed and testicular
      pain continues to diminish the patient's quality of life, orchiectomy may have to
      be considered. In general, however, we recommend that surgery be undertaken only
      when a pathologic condition is found and not for pain relief alone.

PMID- 7567717
TI  - Stress ulcer prophylaxis. Do critically ill patients need it?
AB  - Critically ill patients who have a coagulopathy or require mechanical ventilation
      or high-dose corticosteroids are at increased risk for significant stress-related
      gastrointestinal hemorrhage. Unfortunately, it is not clear that prophylaxis has
      any impact on the incidence of bleeding or its outcome. When preventive therapy
      seems warranted, sucralfate (Carafate) is a good first choice if the patient has
      a nasoenteric tube in place. If not, histamine2 blockers in fixed doses by either
      continuous infusion or bolus can be used.

PMID- 7567718
TI  - Preoperative cardiac evaluation. Assessing risk before noncardiac surgery.
AB  - Primary care physicians are often asked to evaluate a surgical candidate's
      cardiovascular and general health status. In some patients, history taking and
      physical examination provide enough information to assess risk for the proposed
      procedure. In others--especially those with cardiac risk factors--more extensive
      testing is required, such as electrocardiography, stress testing, or angiography.
      Once clearance for surgery has been given, primary care physicians can suggest
      risk-reduction strategies that may help to minimize perioperative morbidity or
      mortality.

PMID- 7567719
TI  - Lower extremity injuries in runners. Helping athletic patients return to form.
AB  - Running injuries are primarily musculoskeletal, usually the result of a change in
      training regimen or technique. A sudden increase in mileage is the most common
      cause. Athletes who run more than 40 miles a week have an increased risk of
      injury. Most injuries affect the knee, but the shin, ankle, and foot are also
      common sites. The RICE protocol (rest, ice, compression, and elevation) is useful
      in most cases, although more aggressive treatment, including surgery, is
      sometimes indicated. Primary care physicians should be familiar with the
      diagnosis and treatment of common running injuries and be aware of conditions
      requiring referral.

PMID- 7567720
TI  - Hearing loss. A plan for individualized management.
AB  - Because some cases of hearing loss demand urgent attention, an approach to
      patients with hearing loss should be adopted in the primary care setting that
      allows for systematic institution of an individualized and appropriate treatment
      plan. Workup is enhanced by categorizing the hearing loss as acute or chronic and
      conductive or sensorineural. The Rinne and Weber tuning fork tests are the most
      important tools in distinguishing between conductive and sensorineural hearing
      loss. The patient history and otologic examination also provide diagnostic clues.
      Treatment depends on the cause and the type of hearing loss.

PMID- 7567722
TI  - Looking for silver linings.

PMID- 7567721
TI  - Breathlessness. Strategies aimed at identifying and treating the cause of
      dyspnea.
AB  - The cause of dyspnea should always be assumed to be physical in nature, although
      a psychological component may sometimes exist. The workup should include thorough
      history taking, physical examination, chest radiography, electrocardiography, and
      determination of arterial blood gas levels or pulse oximetry readings. Although
      pulse oximetry provides a rough approximation of tissue perfusion, it is less
      useful for the diagnosis of hypoxia or abnormalities of ventilation. It may be
      used to assess oxygenation when the cause of dyspnea is known. It is also useful
      to monitor the clinical course during treatment, which should be directed to the
      underlying process.

PMID- 7567723
TI  - Screening and diagnostic breast imaging procedures. A look at lesions through a
      radiologist's eyes.
AB  - Breast cancer is the most common cancer among American women, and primary care
      physicians can be instrumental in ensuring a timely diagnosis. Women should be
      taught breast self-examination by the time they are in their late teens. Patients
      of all ages should be encouraged to have regular physician-conducted breast
      examinations and mammographic screening at a high-quality center. The consistent
      care and individualized follow-up provided in a primary care office are vital
      components of the total effort toward good breast health.

PMID- 7567724
TI  - Local and regional therapy for primary breast tumors. Answers to major questions.
AB  - Because all primary care physicians see patients with breast cancer, it is
      imperative that they maintain an up-to-date working knowledge of its diagnosis
      and treatment. The diagnosis of breast cancer requires awareness and diligence on
      the part of both physician and patient, and surgical consultation is most
      appropriate before any invasive diagnostic procedures are done. The ultimate
      treatment plan evolves from consideration of tumor- and patient-related factors.
      Of these, the ratio of tumor size to breast size, the invasiveness and
      distribution of the tumor, and the individual patient's attitude and concerns are
      most important.

PMID- 7567725
TI  - Adjuvant systemic therapy for breast cancer. Issues for primary care physicians.
AB  - Chemotherapy, hormone therapy, or both are used for adjuvant management in
      patients with breast cancer. Early systemic therapy can delay and possibly
      prevent the progression of micrometastatic disease. Positive axillary nodes
      constitute the major risk factor for later systemic disease, and most oncologists
      believe that all women with positive nodes should have adjuvant therapy. In
      patients with negative nodes, tumor size is apparently the most important factor.
      The prognosis is excellent when the lesion is smaller than 1 cm, and adjuvant
      therapy can probably be avoided. However, therapy is generally advisable when the
      tumor is larger than 2 cm. Although intense scheduled follow-up is beneficial for
      some patients, it is costly and does not always result in a survival advantage.
      Asymptomatic patients may do well with considerably less routine testing.

PMID- 7567726
TI  - Psychosocial issues in breast cancer. Helping patients get the support they need.
AB  - Patients are becoming increasingly involved in making informed choices regarding
      their care. However, in the case of breast cancer, more than medical treatment of
      a body part is at stake. The breast is an important cultural symbol of femininity
      and an intimate part of the patient's self-esteem. The disease and its treatment
      may cause ongoing sadness, fear, anxiety, and anger. Primary care physicians,
      because of their close relationship with patients, are often in a position to
      notice when natural and reasonable emotional reactions go too far or last too
      long. Sensitive support and education of patients who are trying to choose a
      treatment method may minimize anxiety. Formal programs, such as the American
      Cancer Society's Reach to Recovery and Look Good... Feel Better, can be very
      supportive. For interested patients, support groups provide a chance to freely
      express their thoughts and feelings. However, not all women wish to participate
      in programs and groups. In some cases, careful listening on the part of the
      primary care physician is the most powerful intervention.

PMID- 7567729
TI  - Radiotherapy and chemotherapy for inoperable non-small cell lung cancer.
AB  - Non-small cell lung cancer is a major cause of mortality and significant
      morbidity in the UK. The majority of patients are inoperable and the optimum
      management of these patients requires a multidisciplinary approach involving the
      cooperation of respiratory physicians, thoracic surgeons and clinical oncologists
      (radiotherapists). Treatment techniques are constantly being refined and new
      approaches developed.

PMID- 7567728
TI  - The management of anticoagulation in patients with prosthetic heart valves
      undergoing non-cardiac operations.
AB  - Prosthetic valve thrombogenicity and bleeding complications associated with life
      long anticoagulation are constant potential causes of morbidity and mortality
      following prosthetic valve implantation. The conflict between over- and under
      anticoagulation is even more of a problem when other surgical interventions are
      required. Very few clinical trials have addressed this issue. We propose some
      guidelines based on the concept of risk-adjusted intensity of anticoagulation but
      stress the need for caution with interpretation of these recommendations.

PMID- 7567727
TI  - Communicating with young adults with cystic fibrosis.
AB  - The care of the young adult with cystic fibrosis is complex, requiring a
      multidisciplinary input from different carers. Communication with and education
      of patients covers many areas; topics may include medical and personal problems,
      transplantation, survival, current scientific breakthroughs and the future.
      Communicating in these areas with knowledgeable young adults requires skill, tact
      and self-education upon the part of the cystic fibrosis team.

PMID- 7567730
TI  - The changing context of undergraduate medical education.
AB  - It has long been recognised that intensive efforts are needed to reform medical
      education in order to meet the future needs of populations worldwide. Pressure
      for changes to the organisation, content and delivery of both undergraduate and
      postgraduate medical education has greatly increased in the last two decades. The
      experience of innovative medical schools, the emergence of learner-centred
      teaching methods and the implications of health-care reforms in North America and
      Britain are major factors influencing calls for change. The pace of change has
      accelerated to such an extent in recent years that progress towards widespread
      reform appears to be more attainable than ever before. This article provides an
      overview of the changing context of health-care, some patterns of existing
      medical education and some strategies for change.

PMID- 7567731
TI  - Drug treatment of toxoplasmic encephalitis in acquired immunodeficiency syndrome.
AB  - Toxoplasma gondii is a ubiquitous parasite, which causes several serious
      diseases. Until the AIDS pandemic, toxoplasmic encephalitis was largely confined
      to the pharmacologically immune-suppressed and to cases of congenital
      transmission. T gondii is now one of the more commonly encountered opportunistic
      pathogens of advanced AIDS.

PMID- 7567732
TI  - Giant hydronephrosis in adults: the great mimic. Early diagnosis with ultrasound.
AB  - Giant hydronephrosis in adults is uncommon and often misdiagnosed clinically. We
      present three cases of giant hydronephrosis in adults secondary to ureteric
      calculous obstruction, two of whom presented with an acute abdomen and one with
      an indirect inguinal hernia. All patients were diagnosed promptly with
      ultrasound.

PMID- 7567733
TI  - The economic and quality-of-life benefits of Helicobacter pylori eradication in
      chronic duodenal ulcer disease--a community-based study.
AB  - A policy of Helicobacter pylori eradication in patients with duodenal ulceration
      on long-term acid-suppressing therapy was evaluated in a prospective study
      amongst a general practice population, with particular reference to economic and
      quality-of-life benefits. One hundred and sixty-eight patients on long-term acid
      suppressing therapy had chronic duodenal ulcer disease of whom 88 were eligible
      for the study; 45 patients attended for review, with 42 testing positive for H
      pylori (as assessed by 13C-urea breath test). The median duration of acid
      suppressing therapy was six years (maximum 15 years); 47.6% of the patients were
      using additional antacids and 80.9% still experienced epigastric discomfort. Two
      thirds (28/42) of the patients eradicated H pylori. Successful eradication was
      associated with a highly significant reduction in all symptoms. At 12 months
      follow-up, heartburn had decreased from 28.7% to 7.1%, epigastric discomfort from
      75% to 3.6%, nausea from 32.1% to 0% and wind from 50% to 0%. Of the patients
      that eradicated H pylori 96.4% reported an improvement in their general health
      compared to none of those that remained H pylori positive. Successful H pylori
      eradication therapy scored higher on satisfaction ratings than long-term acid
      suppressing therapy. Eradication of H pylori resulted in 27/28 patients being
      able to discontinue acid-suppressing therapy, representing a 5.8% reduction in
      the use of such drugs per year in the local general practice population. A policy
      of H pylori eradication in chronic duodenal ulcer disease reduces the use of long
      term acid-suppression therapy in general practice. This has important financial
      implications as well as offering considerable symptomatic benefits to the
      patients and improving their quality of life.

PMID- 7567734
TI  - Kerosene poisoning in children in Iraq.
AB  - One hundred and three children with kerosene poisoning were studied. The majority
      of the patients were under five years of age and included a newborn baby. More
      patients were seen in spring and fewer in winter months. Most of the patients
      were children of poor families living in overcrowded conditions. Negligence and
      ignorance were the main causes of poisoning. Respiratory and central nervous
      systems were mainly involved. Chest X-ray abnormalities were frequently seen. The
      patients were treated symptomatically. Only one patient died, he had been in a
      coma on admission to the hospital. All other patients had rapid and complete
      recoveries.

PMID- 7567735
TI  - Abdominal pain.

PMID- 7567736
TI  - Visual impairment in a woman with histiocytosis.

PMID- 7567737
TI  - An unusual cerebral mass lesion.

PMID- 7567739
TI  - Pulse oximetry monitoring during non-sedated upper gastrointestinal endoscopy.
AB  - Fifty consecutive patients judged fit for non-sedated upper gastrointestinal
      endoscopy were monitored by pulse oximetry before, during and after the
      procedure. Transient hypoxia developed during intubation in five subjects (10%)
      but treatment was not required nor was the test halted. Only one patient with pre
      existing respiratory problems became hypoxaemic to the extent that oxygen had to
      be given and the procedure halted. The chance of hypoxia was unrelated to age,
      sex, smoking, anxiety, or the duration of intubation. Routine pulse oximetry is
      not necessary for non-sedated gastroscopy but oximetry monitoring may be
      important in selected cases.

PMID- 7567738
TI  - Central pontine myelinolysis: clinical and MRI correlates.
AB  - Central pontine myelinolysis (CPM) is a rare condition characterised by spastic
      tetraparesis, pseudobulbar palsy and the 'locked-in syndrome'. It is frequently
      fatal. We report a patient who developed CPM secondary to profound hyponatraemia
      and who recovered with no disability. Serial magnetic resonance imaging (MRI)
      demonstrated characteristic abnormalities within the pons at the onset of the
      disease, whereas computerised tomography was normal. Clinical improvement was
      followed six months later by progressive resolution of the MRI changes, with
      almost complete resolution after 18 months. Clinical and MRI findings correlate
      early in the course of CPM but clinical recovery predates MRI improvement by
      several months.

PMID- 7567741
TI  - Guillain-Barre syndrome as an extraintestinal manifestation of Crohn's disease.
AB  - A variety of extraintestinal manifestations, probably immune-mediated, may appear
      during relapses of Crohn's disease. We report the clinical observation of a 34
      year-old woman who developed a Guillain-Barre syndrome, aphthous stomatitis and
      oligoarthritis during a relapse of Crohn's ileocolitis. This case suggests that
      the Guillain-Barre syndrome may be another extraintestinal manifestation of
      Crohn's disease.

PMID- 7567740
TI  - Post-typhoid anhidrosis: a clinical curiosity.
AB  - A 19-year-old girl developed generalised anhidrosis following typhoid fever.
      Elaborate investigations disclosed nothing abnormal. A skin biopsy revealed the
      presence of atrophic as well as normal eccrine glands. This appears to be the
      third case of its kind in the English literature. It is postulated that typhoid
      fever might have damaged the efferent pathway of sweating.

PMID- 7567742
TI  - The triple-phase response--problems of water balance after pituitary surgery.
AB  - A 29-year-old woman presenting with persistent headache and oligomenorrhoea was
      found to have a pituitary adenoma which was treated surgically. Postoperatively
      she developed diabetes insipidus which resolved on treatment with desmopressin
      acetate. She represented 11 days post surgery with nausea and vomiting and
      inappropriate antidiuresis was diagnosed in an infectious diseases unit. On re
      admission to our unit cranial diabetes insipidus was confirmed by water
      deprivation. This case demonstrates the need for careful monitoring of patients
      after pituitary and suprasellar surgery or head injury.

PMID- 7567743
TI  - Popliteal vein thrombosis associated with femoral osteochondroma and popliteal
      artery pseudoaneurysm.
AB  - Deep vein thrombosis is a common condition thought to be caused by impaired
      venous blood flow or hypercoagulable blood states. However, often no predisposing
      cause can be found. We describe a deep vein thrombosis formed in association with
      femoral osteochondroma and popliteal artery pseudoaneurysm. It is an interesting
      combination that has only been described once before.

PMID- 7567744
TI  - Synchronous multiple lymphomatous polyposis and adenocarcinomata in the large
      bowel.

PMID- 7567745
TI  - Manubrio-sternal joint sepsis in rheumatoid arthritis.

PMID- 7567746
TI  - Allergic and toxic reaction to alprazolam.

PMID- 7567747
TI  - Chronic myeloid leukaemia and allogenic bone marrow transplantation in a patient
      with toxic oil syndrome.

PMID- 7567748
TI  - Proptosis, skull infarction and epidural haematoma in sickle thalassemia.

PMID- 7567749
TI  - Telling your patient he/she has multiple sclerosis.
AB  - It is difficult to tell a person that s/he has multiple sclerosis. The diagnosis
      is based on clinical findings and often cannot be made on first meeting. In many
      cases investigations do not help. When the diagnosis is made, the patient should
      be fully informed in the majority of cases. Guidelines have been developed for
      imparting the diagnosis. Early diagnosis will become increasingly important with
      the development of new treatments for multiple sclerosis.

PMID- 7567750
TI  - Stents in the oesophagus.
AB  - The use of self-expanding metal stents can markedly improve the care of patients
      with inoperable oesophageal malignancy. The stents can be easily introduced
      without the need for general anaesthesia. They have fewer complications during
      insertion than rigid stents and fewer complications than laser therapy. With
      these stents lumens of up to 2.5 cm are easily obtainable. The article considers
      the type of patient who may be suitable for stenting, the technique of insertion,
      benefits and complications of their use.

PMID- 7567752
TI  - Prescribing in the elderly.

PMID- 7567751
TI  - Cardioversion of atrial fibrillation.
AB  - Cardioversion to sinus rhythm should be considered for all patients in atrial
      fibrillation in order to improve cardiac performance and perhaps to reduce the
      long-term risk of thromboembolic complications. Different methods of
      cardioversion, whether electrical or pharmacological, exist and there is often
      uncertainty about performing the procedure. In particular, there is often
      confusion about the use of anti-arrhythmic drugs and the suitable length of
      anticoagulant therapy required pre- and post-cardioversion. This review discusses
      the current understanding of electrical and pharmacological cardioversion of
      atrial fibrillation, the clinical effects and the role of prophylactic anti
      arrhythmic and anticoagulant therapy in this procedure.

PMID- 7567755
TI  - Angiography and the aetiology of heart failure.
AB  - The diagnosis of idiopathic dilated cardiomyopathy should not be made without
      first performing a coronary angiogram. If the cause of heart failure is unknown
      this should be stated rather than attributing the cause to dilated
      cardiomyopathy. Severe ventricular dysfunction may improve dramatically after
      revascularisation in some cases of coronary disease. Preservation of R waves on
      the surface electrocardiogram suggests the presence of hibernating myocardium but
      thallium scintigraphy or positron emission tomography scanning should be employed
      to investigate this further.

PMID- 7567754
TI  - The quest for a more acceptable bowel preparation: comparison of a polyethylene
      glycol/electrolyte solution and a mannitol/Picolax mixture for colonoscopy.
AB  - Eighty-nine consecutive patients attending for day-case colonoscopy were randomly
      allocated either polyethylene glycol/balanced electrolyte (PEG) mixture (n = 45)
      or a mannitol/Picolax mixture (n = 44). Both preparations were administered in
      two fractions. Patients recorded their experience of the preparation on a
      questionnaire and one of two experienced endoscopists (unaware of the type of
      preparation given) assessed the result of bowel cleansing. Carbon dioxide
      insufflation was used for all examinations. Good/excellent bowel cleansing
      occurred in significantly more patients given PEG, 43 (96%), than those allocated
      mannitol/Picolax, 34 (77%), p = 0.01. More patients receiving mannitol/Picolax
      were able to complete the preparation in full than patients receiving PEG (38 vs
      27, p = 0.01). More patients found the taste of mannitol/Picolax pleasant
      compared to PEG (46% vs 20%). Both preparations had a similar side-effect
      profile. Of those patients tested, 13% receiving mannitol/Picolax had a postural
      drop in blood pressure and blood parameters suggestive of mild dehydration. A
      fractionated administration of PEG as a bowel preparation for day-case
      colonoscopy is well tolerated and superior as a cleansing agent to a
      mannitol/Picolax combination. Provided carbon dioxide is used as the insufflating
      agent, mannitol/Picolax is an acceptable alternative in fit, young patients
      intolerant of PEG.

PMID- 7567756
TI  - An unusual cause of dementia.
AB  - Gliomatosis cerebri is a rare cerebral tumour that presents with personality and
      mental state changes. Diagnosis can be very difficult and many times is made at
      post mortem. We describe a 63-year-old man who presented initially with
      depression that merged into a schizophrenia-like illness, and who developed
      progressive dementia prior to his death. Two computed tomography (CT) scans of
      the brain were normal and the diagnosis of gliomatosis cerebri was made at post
      mortem. The progressively changing mental state was suggestive of an organic
      cause of his illness. Since this tumour may not be detected by a CT scan, a
      magnetic resonance imaging scan with T2-weighted images with spin echo sequences
      of the brain should be performed. Prognosis is very poor but diagnosis is
      important to plan terminal care. The patient described was unusual because he was
      older than most people with this tumour, and he presented with psychiatric
      symptoms which were thought to be non-organic for almost two years.

PMID- 7567753
TI  - An audit of fatal acute pancreatitis.
AB  - Acute pancreatitis has a mortality of about 10%: this figure has not changed over
      the last 20 years. A retrospective audit of fatal acute pancreatitis was
      performed in a teaching hospital with a catchment population of about 750,000
      patients to examine patient characteristics. Using Hospital Activity Analysis
      code 577.0, all fatal cases of acute pancreatitis were studied in a six-year
      period 1987-93. Additionally, all post mortem diagnoses of acute pancreatitis
      were traced. The overall post mortem rate in Nottingham at the time of the study
      was about 35%. All available records, X-ray and biochemical data were studied and
      appropriate information recorded and analysed for 65 fatal cases. Only 15% were
      post mortem diagnoses, lower than in previous series; 72% had respiratory and 67%
      had renal complications. Only 34% had been admitted to the intensive care unit. A
      third of patients had had surgery; 67% of these was some form of external
      drainage. Of the 14 patients with proven gallstone pancreatitis only three had
      endoscopic retrograde cholangiopancreatography; 42% of patients had idiopathic
      disease. Not all the patients diagnosed ante mortem had the full biochemical
      predicted severity criteria analysed: pO2 and calcium analysis was performed in
      about 80%. Pre-mortem diagnoses of pancreatitis was achieved more frequently than
      in other comparable series.

PMID- 7567757
TI  - Neurofibromatosis and insulinoma.
AB  - A 45-year-old man with neurofibromatosis presented with recurrent seizures due to
      hypoglycaemia caused by an insulinoma. The attacks were abolished after the
      successful removal of the insulinoma. This probably represents another example of
      the association between neurofibromatosis and a tumour consisting of cells with
      amine-precursor-uptake and decarboxylation.

PMID- 7567758
TI  - Cerebral venous sinus thrombosis and antiphospholipid antibodies.
AB  - We report two cases of cerebral venous sinus thrombosis associated with an
      antibody to phospholipids, namely the lupus anticoagulant. Both patients later
      developed further immunologically mediated conditions. The importance of
      screening for the lupus anticoagulant in addition to anticardiolipin antibodies
      in this condition and the need for follow-up of such patients is discussed.

PMID- 7567759
TI  - Liver abscess and disseminated intravascular coagulation in tuberculosis.
AB  - We report the case of a 55-year-old man with chronic renal failure, and a history
      of prolonged fever and jaundice. Radiological studies revealed a multiloculated
      irregular liver abscess. Mycobacterium tuberculosis was isolated from the abscess
      on smear and culture of aspirated pus. Haematological studies revealed the
      presence of disseminated intravascular coagulation. A detailed search failed to
      identify any reason for this other than the tuberculous infection. The treatment
      of tuberculous liver abscess and pathogenesis of disseminated intravascular
      coagulation in tuberculosis are discussed.

PMID- 7567761
TI  - Pellagra complicating Crohn's disease.
AB  - We report a 53-year-old patient with clinical features of pellagra as a
      complication of Crohn's disease. His symptoms improved rapidly on taking oral
      nicotinic acid and vitamin B complex. We suggest the paucity of reported cases of
      pellagra in Crohn's disease is a reflection of poor recognition of this
      complication.

PMID- 7567760
TI  - Peliosis of the spleen: possible association with chronic renal failure and
      erythropoietin therapy.
AB  - Splenic peliosis was identified at necropsy in a 62-year-old woman receiving
      continuous ambulatory peritoneal dialysis for end-stage renal failure, and
      erythropoietin therapy for uraemia and anaemia. The immediate cause of death was
      arrhythmia related to ischaemic heart disease, following an episode of
      intramuscular haematoma (secondary to platelet dysfunction). The unusual
      association between peliosis and renal failure, and possibly erythropoietin
      therapy, is discussed.

PMID- 7567762
TI  - Iatrogenic profound hypoalphalipoproteinaemia: an unrecognised cause of very low
      HDL cholesterol.
AB  - A significant reduction in plasma high density lipoprotein (HDL) cholesterol is a
      recognised consequence of treatment with probucol. By contrast, fibrate therapy
      in general has the opposite effect. We report two cases where the combination of
      probucol and a fibrate led to profoundly reduced plasma levels of HDL cholesterol
      associated with very low levels of apolipoprotein A-I (apoA-I). In the first,
      bezafibrate was added to probucol, and in the second, probucol added to a
      combination of simvastatin and fenofibrate. In both cases, plasma levels of HDL
      and apoA-I returned towards normal after discontinuation of one or both drugs,
      indicating that the reduction was reversible.

PMID- 7567763
TI  - Polymyalgia rheumatica, temporal arteritis and malignancy.
AB  - The use of steroid therapy in polymyalgia rheumatica and temporal arteritis is
      necessary and usually effective, but may mask coexisting disease. The importance
      of early consideration of other disorders in such patients is illustrated by
      three case histories.

PMID- 7567764
TI  - Dysphagia due to secondary achalasia as an early manifestation of squamous cell
      carcinoma.
AB  - A 59-year-old man, a smoker, presented with features of airflow obstruction due
      to squamous cell carcinoma of central airways mimicking chronic obstructive
      airways disease. He also had pronounced dysphagia. Computed tomographic and
      magnetic resonance imaging scans showed mediastinal tumour invasion but no direct
      oesophageal involvement. Oesophageal manometry studies revealed that dysphagia
      was due to the oesophageal motility disorder, secondary achalasia.

PMID- 7567766
TI  - Fever and a painful knee.

PMID- 7567765
TI  - Abdominal mass in a patient with Crohn's disease.

PMID- 7567767
TI  - ACE inhibitors in heart failure. What dose?

PMID- 7567769
TI  - Renal failure due to cholesterol embolism.

PMID- 7567768
TI  - Cigarette smoking and sore throats in adults.

PMID- 7567770
TI  - The parents of a severely dependent child.

PMID- 7567771
TI  - Managing painful upper limb disorders.

PMID- 7567772
TI  - Reflex sympathetic dystrophy.

PMID- 7567774
TI  - Success with erectile dysfunction.

PMID- 7567773
TI  - The MRCGP--the standard to set yourself.

PMID- 7567775
TI  - Bacterial vaginosis: the case for treatment.

PMID- 7567776
TI  - Identifying and treating genital warts.

PMID- 7567777
TI  - Tackling vulval problems.

PMID- 7567778
TI  - Sexual infections in the antenatal patient.

PMID- 7567780
TI  - High throughput assays of cloned adrenergic, muscarinic, neurokinin, and
      neurotrophin receptors in living mammalian cells.
AB  - Many receptors stimulate proliferation of NIH 3T3 cells in a ligand dependent
      fashion. Based on this observation, we developed a high throughput assay of
      cloned receptor pharmacology. In this assay, receptors are transiently co
      expressed with the marker enzyme beta-galactosidase. Receptors that induce
      cellular proliferation select and amplify the cells that also express the marker,
      thus the ability of ligands to alter receptor activity are reported as changes in
      enzyme activity. In the present study, we used this assay to evaluate the ability
      of agonist ligands to stimulate four cloned receptors. The agonists
      phenylephrine, carbachol, substance P and nerve growth factor selectively
      stimulated cells transfected with the alpha-1b adrenergic, m4 muscarinic, NK1
      neurokinin and trkA neurotrophin receptors, respectively. These data demonstrate
      that a high throughput colorimetric assay performed in 96 well plates can be used
      to evaluate the pharmacology of ligands for cloned receptors belonging to a wide
      range of functional and pharmacological classes.

PMID- 7567781
TI  - Ionotropic glutamate receptors--focus on non-NMDA receptors.

PMID- 7567779
TI  - Characterization of a P2Y purinoceptor in the brain.
AB  - Little has been known of the abundance in the brain of any of the G protein
      coupled P2 purinoceptors nor their pharmacology. Here we show that [35S]dATP
      alpha S is a suitable radioligand for investigating these receptors and hence
      that they are exceptionally abundant both in one-day-old chick (Bmax: 37 pmol
      agonist sites/mg protein) and adult rat brain membranes (Bmax: 39 pmol/mg
      protein). [35S]dATP alpha S (which is selective for P2Y over the P2X types of
      purinoceptor) binds with high affinity to these sites in the chick (Kd: 13.3 nM)
      and in the rat brain membranes (Kd: 9.1 nM). The rank order of potency of
      purinoceptor-active agonists and antagonists displacing [35S]dATP alpha S binding
      is: dATP alpha S > (3'-deoxyATP, 2-methylthioATP, ATP alpha S, ATP) > 2'-deoxyATP
      > 2-methylthioADP > ADP >> suramin, Reactive Blue-2 >> UTP, L-beta,gamma
      methyleneATP, adenosine; this defines these binding sites as P2Y subtypes of the
      P2 purinoceptors. This pharmacological profile of purinergic ligands is in
      excellent agreement with the potency order established for the recombinant P2Y1
      purinoceptor from chick brain, identifying the great majority of the brain P2
      purinoceptors as identical or very similar to the native P2Y1 receptor.

PMID- 7567782
TI  - Does the dopamine receptor subtype selectivity of antipsychotic agents provide
      useful leads for the development of novel therapeutic agents?
AB  - Antipsychotic agents share the ability to antagonize dopamine (DA) receptors, and
      correlation studies have indicated that the clinical efficacy of neuroleptic
      agents may be coupled to their affinity for D2 receptors. More recently, a family
      of DA D2-like receptors has been identified. These receptors include the D2A,
      D2B, D3 and D4 receptors. On the basis of in vitro receptor-binding studies, it
      has been suggested that the atypical profile of clozapine might be related to a
      selective effect on the D4 receptor subtype. We have studied the receptor-binding
      profiles of a series of antipsychotic agents and evaluated some of the compounds
      in behavioural assays in the rat. Most of the antipsychotic agents lack
      selectivity for DA-receptors as well as selectivity for the various DA-receptor
      subtypes. Because of this lack of selectivity, it is impossible to draw firm
      conclusions about the role of any particular receptor in the clinical profile of
      the neuroleptic agents. Furthermore, the pharmacology of potential human
      metabolites has to be taken into account in a proper analysis of the clinical
      profile. Consequently, most speculations on the key-target of clinically
      interesting antipsychotics (including clozapine) may be of little practical
      value. Clinical studies with receptor (subtype)-selective agents will be more
      informative.

PMID- 7567783
TI  - Cell systems for use in studies on the relationship between foreign compound
      metabolism and toxicity.
AB  - Since the metabolism of most foreign compounds is predominantly controlled by
      hepatic in metabolism, isolated hepatocytes in most cases quite well predict the
      pattern of the overall metabolism of a given compound. Methods have been
      developed for cryopreserving isolated hepatocytes from man and other species with
      satisfactory maintenance of foreign compound metabolizing enzyme activities. The
      installation of a bank of cryopreserved hepatocytes from different species is
      possible and may be used for rational species extrapolation. It is necessary for
      some toxicological investigations to have hepatocytes which retain their
      differentiated status in culture for a sufficient time period. This might be
      achieved by co-culturing hepatocytes with diverse cell lines. However, from one
      cell line to the other differences in the pattern of stabilization of individual
      hepatocyte functions are found. In addition, questions on metabolic action of
      individual isoenzymes can also be addressed by the use of genetically engineered
      cell lines. All the in vitro systems mentioned, especially those which contain
      differentiated human cells or human isoenzymes are helpful in the rational
      species extrapolation of toxic effects from animal to man.

PMID- 7567785
TI  - Frontiers in the development of new medicines in relation to clinical
      pharmacology.

PMID- 7567786
TI  - Serotonin--an intestinal secretagogue--receptor subtypes and intracellular
      mediators.

PMID- 7567784
TI  - Human dioxin receptor chimera transactivation in a yeast model system and studies
      on receptor agonists and antagonists.
AB  - A yeast dioxin receptor chimera model has been developed to study ligand binding
      and transactivation properties of the human dioxin receptor. Using this new yeast
      model, the human dioxin receptor chimera was found to possess a constitutive
      transactivity on a LacZ reporter gene, however, the transactivation by the
      chimera was enhanced by the addition of several polycyclic aromatic hydrocarbons
      to the culture medium. The order of best polycyclic aromatic hydrocarbon inducer
      to worst correlated well with the known in vitro dioxin receptor binding
      affinities for these polycyclic aromatic hydrocarbons. 7,8-Benzoflavone, a weak
      dioxin receptor agonist and strong antagonist of the mammalian dioxin receptor
      also behaved as a weak agonist and strong antagonist of the human dioxin receptor
      chimera expressed in yeast. The implications for these findings as well as the
      utility of this new yeast human dioxin receptor chimera model are discussed.

PMID- 7567787
TI  - Biologic, immunocytochemical, and cytogenetic characterization of two new human
      melanoma cell lines: IIB-MEL-LES and IIB-MEL-IAN.
AB  - Two human melanoma cell lines, derived from metastases of two patients with
      epithelioid malignant amelanotic melanomas, and designated IIB-MEL-LES and IIB
      MEL-IAN, have been established. Both cell lines have been in continuous culture
      over 2 years and were propagated continuously for 85 and 75 serial passages,
      respectively. Morphologically, IIB-MEL-LES is composed predominantly of spindle
      shaped cells, whereas IIB-MEL-IAN grows as a monolayer of cuboid and stellate
      shaped cells with many rounded cells in suspension. Immunocytochemical studies
      revealed that both cell lines express S-100 protein, vimentin, and GD3 and GD2
      gangliosides but are negative for keratin and collagen. Both cell lines express
      HLA class I and HLA-DR antigens in variable proportions. The MAGE-1 gene is
      expressed only by the IIB-MEL-IAN cell line, as revealed by PCR analysis.
      Cytogenetic analysis of both cell lines revealed abnormal karyotypes; the modal
      chromosome numbers of IIB-MEL-LES and IIB-MEL-IAN were 48 and 81, respectively.
      IIB-MEL-LES cells presented rearrangements in chromosomes 1, 14 and X, gains in
      chromosomes 10, 20, and 21 losses in chromosomes 15 and Y. The most frequent
      markers observed in IIB-MEL-IAN cells were 7q+, 10p+, 2p+, i(6p), 2q+, and 10q-.
      Clonal gains were observed in chromosomes 12 and 21, whereas losses were seen in
      chromosomes 1, 2, 3, 4, 6, 7, 11, and 17. Both cell lines were capable of forming
      colonies in soft agar and developed tumors when transplanted into nude mice,
      reproducing and maintaining the characteristics of the original tumors. These
      cell lines and their xenografts appear to provide useful systems for studying the
      biology, genetics and histogenesis of human malignant melanoma and could be
      utilized for the development of melanoma vaccines.

PMID- 7567788
TI  - Seasonal variation in serum concentration of 5-S-cysteinyldopa and 6-hydroxy-5
      methoxyindole-2-carboxylic acid in healthy Japanese.
AB  - Serum concentrations of 5-S-cysteinyldopa (5-S-CD) and 6-hydroxy-5-methoxyindole
      2-carboxylic acid (6H5MI2C) have been used as biochemical markers of melanoma
      progression. We examined the effect of solar radiation on serum levels of 5-S-CD
      and 6H5MI2C in 10 healthy Japanese by measuring these markers every month during
      a period of 2 years. 5-S-CD levels were higher in early summer and lower in early
      winter. The difference in the average levels was approximately twofold, but among
      the 240 samples, no individual values exceeded the upper limit of normal value,
      10 nmol/L. A significant correlation (P < 0.02) was observed between 5-S-CD level
      and solar radiation. 6H5MI2C levels showed a smaller variation than 5-S-CD. No
      correlation was observed between 6H5MI2C level and solar radiation. This study
      showed that serum 5-S-CD and 6H5MI2C in healthy Japanese did not exceed the upper
      limit of normal values even in sunny season.

PMID- 7567789
TI  - Atypical androgen receptor in the human melanoma cell line IIB-MEL-J.
AB  - To evaluate the presence of androgen receptors in the human melanoma cell line
      IIB-MEL-J, a Scatchard plot analysis was performed. Cells in culture revealed a
      single binding component with an apparent dissociation constant (KD) at 37
      degrees C of 11 nM and a binding capacity of 326 fmol/mg protein when measured
      with [3H]-R1881. Competition analysis revealed an atypical relaxation of
      specificity, since not only androgen (testosterone, dihydrotestosterone [DHT],
      R1881) and antiandrogen (hydroxy-flutamide [OH-FLU]) competed for [3H]-R1881
      binding, but also estradiol, progesterone, and cortisol at 500-fold excess
      concentration. Binding of [3H]-estradiol and [3H]-R5020 in the absence of
      unlabeled DHT were completely suppressed in its presence. Immunohistochemistry of
      androgen receptor with a monoclonal antibody showed that nuclei were vigorously
      stained. Different doses of flutamide (FLU) and OH-FLU tested on cultured IIB-MEL
      J cells in the presence of serum inhibited significantly cell proliferation in a
      dose-dependent manner. When cells were incubated with 10 nM DHT and 1% charcoal
      adsorbed serum, a significant stimulation of growth that was observed was
      inhibited by 4 microM OH-FLU. DHT stimulation was completely reversed by the
      antiestrogen tamoxifen. In addition, male nude mice transplanted with IIB-MEL-J
      tumor were treated with FLU when tumors were palpable. FLU was effective in
      diminishing tumor growth and increasing survival rate of the animals. As a
      conclusion, the presence of functional androgen receptors in these cells has been
      demonstrated by growth inhibition in vitro and in vivo with antiandrogens, and
      their atypical nature is suggested by binding cross-reactivity and competition
      studies.

PMID- 7567791
TI  - Characterization of the melanogenic system in Vibrio cholerae, ATCC 14035.
AB  - The nature of the pigment formed by Vibrio cholerae and the characterization of
      its biosynthetic pathway is shown. This microorganism is able to synthesize
      melanin-like pigment when cultured in the presence of L-tyrosine. Other phenolic
      chemicals related to L-tyrosine do not lead to pigment production. The
      microorganism has no tyrosine hydroxylase activity, and the levels of dopa
      oxidase activity are very low, making the existence of a tyrosinase very
      unlikely. However, Vibrio cholerae contained transaminases that transforms L
      tyrosine into p-hydroxyphenylpyruvate. Moreover, Vibrio cholerae is able to go
      further in the catabolic pathway, releasing a great amount of homogentisic acid.
      This acid can spontaneously be oxidized to its p-quinone form, which subsequently
      polymerizes leading to pigment formation. It is concluded that the pigment formed
      by Vibrio cholerae is not synthesized by the Raper-Mason pathway, but by a L
      tyrosine catabolism pathway leading to homogentisic acid. Some simple properties
      of that melanin are compared to model eu- and pheomelanin, but no clear
      distinction could be stated, indicating the similarity between all these
      pigments.

PMID- 7567793
TI  - Influences of sex, castration, and androgens on the eumelanin and pheomelanin
      contents of different feathers in wild mallards.
AB  - In mallards the bright nuptial plumage of the drake represents the neutral, sex
      hormone-independent coloration of the species that both sexes eventually exhibit
      after castration. We compared the pheo- and eumelanin contents of feathers from
      the head, breast, flank, and under-tail coverts in five groups of mallards after
      the post-nuptial molt in summer: intact hens, intact drakes, castrated drakes,
      castrated drakes injected with testosterone during the spring, and castrated
      drakes injected with 5 alpha-dihydrotestosterone during the spring. In the head
      feathers and under-tail coverts, the gonadal hormones of the intact birds and the
      testosterone injections into castrates significantly reduced the eumelanin
      content, tended to increase the pheomelanin content, and, thereby, changed the
      melanin type from eumelanic in the untreated castrates to mixed melanic in the
      other three groups. The eumelanin contents of the flank feathers did not differ
      among the groups, but the pheomelanin contents at this site was significantly
      elevated in the two intact groups and the testosterone-treated compared to the
      uninjected castrates. Again, the melanin type changed from eumelanic in the
      castrates to mixed melanic in the other three groups. The high pheomelanin
      content of the breast feathers in the castrated birds was significantly reduced
      in the hens, intact drakes, and testosterone-injected castrates with a
      concomitant tendency for elevated eumelanin contents. At this site, a change
      occurred from pheomelanic to mixed melanic. 5 alpha-dihydrotestosterone was
      clearly less effective than testosterone in affecting the melanin contents in
      castrates and resulted in an intermediate coloration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7567790
TI  - Corticotropin expression by human melanocytes in the skin.
AB  - Highly dendritic melanocytes have been observed in rapidly proliferating
      seborrheic keratosis, epidermis overlying melanomas, and in melanomas. On
      staining for the presence of POMC with monoclonal antibody against human ACTH,
      the melanocytes show cytoplasmic positivity. Short term organ cultures of whole
      skin from the marginal zone of vitiligo patients show that 22.7% of controls and
      45.5% on dark incubation in adriamycin and 87.5% exposed to a pulse of UV on
      adriamycin treatment show melanocytes positive for ACTH. The surrounding
      keratinocytes in the epidermis and in the seborrheic keratosis are negative,
      whereas in melanomas, isolated groups of melanocytes are positive for ACTH. These
      findings indicate that ACTH is expressed by the melanocytes in the G2-phase, the
      activity being enhanced on UV exposure. Thus UV dependent pigmentation is
      associated with POMC production in human skin. From this work it is evident that
      the melanocyte network varies the MSH/ACTH levels in correlation with
      repigmentation and depigmentation in the marginal zone in vitiligo by expressing
      POMC locally and is related to the UV-sensitivity of the melanocytes.

PMID- 7567792
TI  - Comparative analysis of melanins and melanosomes produced by various coat color
      mutants.
AB  - Pigmentation in the skin, hair, and eyes of animals is influenced by a number of
      genes that modulate the activity of melanocytes, the intervention of enzymatic
      controls at different stages of the melanogenic process, and the physico-chemical
      properties of the final pigment. The results of combined phenotypic,
      ultrastructural, biochemical, and chemical analyses of hairs of a variety of
      defined genotypes on a common genetic background performed in this study are
      consistent with the view that pigmentation of dark to black hairs results from
      the incorporation of eumelanin pigments whereas that of yellow hairs results from
      the incorporation of eu- and pheomelanins. It is also clear that relatively minor
      differences in melanin content can have dramatic effects on visible hair color. A
      good correlation was found for expression of (and enzyme activities associated
      with) TRP1 and TRP2 with eumelanin synthesis and eumelanosome production.

PMID- 7567795
TI  - Invited commentary: absence of intervillous blood flow in the first trimester of
      human pregnancy.

PMID- 7567797
TI  - Effect of chlorpromazine on the synthesis of neutral lipids and phospholipids
      from [3H]glycerol in the primordial human placenta.
AB  - Addition of chlorpromazine (CPZ) of 100 microM final concentration to fragments
      of primordial human placenta incubated in vitro with [3H]glycerol results in the
      following changes in the labelling of various neutral lipids and phospholipids:
      (1) rapid accumulation of [3H]phosphatidic acid (PA) to a 2.31 +/- 0.12-fold
      (mean +/- s.d., P < 0.05) higher steady-state level within 5 min; (2) a dramatic,
      5-6-fold (5.74 +/- 0.31, P < 0.01) increase in [3H]phosphatidylinositol (PI)
      synthesis within 5-10 min, followed by progressive PI accumulation; (3) gradual
      accumulation of [3H]1,2-diacylglycerol (DAG) reaching approximately 1.7-fold
      (1.72 +/- 0.14, P < 0.05) higher steady-state level at 30 min; and (4) an
      approximately 20 and 30% decrease in [3H]triacylglycerol (TG) and
      [3H]phosphatidylcholine (PC) formation, respectively, which begins to become
      evident between 10-30 min. As dose-response studies indicate, accumulations of PI
      and DAG are most susceptible to CPZ. They respond in the concentration range of
      10-50 microM, while only higher drug concentrations (100-250 microM) affect the
      synthesis of PA, PC and TG significantly. Finally, dioctanoylethyleneglycol
      (DOEG), a structural analogue of the diacyl moiety of PA and DAG, selectively
      inhibits the basal synthesis (0.59 +/- 0.15, P < 0.05) as well as the CPZ-induced
      rise (0.49 +/- 0.11, P < 0.02) of PI. These results suggest that CPZ-induced
      increase in the concentrations of PI and 1,2-DAG may interfere with signal
      transduction pathways in the placenta of pregnant patients treated with CPZ.
      Furthermore, DOEG is able to antagonize the CPZ effect which directs lipid
      biosynthesis towards the formation of PI.

PMID- 7567794
TI  - Current topic: in vivo investigation of the placental circulations by Doppler
      echography.

PMID- 7567796
TI  - Differential distribution of mRNA for the alpha- and beta-subunits of chorionic
      gonadotrophin in the implantation stage blastocyst of the marmoset monkey.
AB  - We studied the expression of mRNA encoding the alpha- and beta-subunits of
      marmoset chorionic gonadotrophin (mCG) in implantation stage blastocysts and in a
      trophoblastic cell line derived from such blastocysts. In this investigation in
      situ hybridization was carried out using digoxygenin-labelled riboprobes to
      localize the subunit transcripts. The trophoblastic cell line, known to secrete
      bioactive mCG, was used as a positive control. Marmoset uterine embryos were
      cultured to hatched blastocysts and following growth on Matrigel or plastic were
      processed for in situ hybridization at developmental stages ranging from 13-15
      days post-conception. In serial sections mCG-beta mRNA was detected mainly in
      polar trophoblast. The mRNA for mCG-alpha was expressed more uniformly in polar
      and mural trophoblast. Transcripts for the beta-subunit were not expressed, or
      present as weak signals, in the inner cell mass (ICM) and endoderm. However, low
      levels of mRNA for mCG-alpha were detected in the ICM and visceral endoderm. We
      have concluded that mRNA for mCG-beta was primarily localized to patches of
      syncytiotrophoblast at the embryonic pole and sparsely distributed in mural
      trophoblast, while the transcripts for mCG-alpha were distributed more uniformly
      in differentiating cytotrophoblast and syncytium, and at much lower levels in ICM
      and early endoderm.

PMID- 7567798
TI  - Localization of amphiregulin in the human placenta and decidua throughout
      gestation: role in trophoblast growth.
AB  - Amphiregulin (AR) is a growth regulatory glycoprotein with significant amino acid
      homology to members of the epidermal growth factor (EGF) family. Its effects are
      mediated via the EGF receptor tyrosine kinase or through specific nuclear
      targeting sequences. In this study, the localization of immunoreactive AR was
      examined in paraformaldehyde-glutaraldehyde fixed, paraffin-embedded human
      placentae and decidua obtained at various stages from 11 weeks to term pregnancy
      using the avidin-biotin complex/peroxidase method. In addition, the effects of AR
      on trophoblast proliferation were evaluated from 3HTdR uptake by first trimester
      human trophoblast cells. Results revealed immunolocalization of AR to the nucleus
      as well as the cytoplasm of the syncytiotrophoblast cell layer of chorionic villi
      until approximately week 18 of gestation after which no immunostaining was
      detected. Villous and extravillous cytotrophoblast cells as well as decidual
      tissue were negative for AR at all gestational ages examined. In the presence of
      exogenous AR, there was a dose-dependent increase in proliferation of the
      trophoblast at AR concentrations ranging from 1-100 ng/ml. These results suggest
      that AR may be an important paracrine or juxtacrine growth stimulatory molecule
      for cytotrophoblast cells in situ early in gestation.

PMID- 7567799
TI  - Cytomegalovirus in the perfused human term placenta in vitro.
AB  - Cytomegalovirus (CMV) is one of the most frequent causes of intrauterine-acquired
      infection in the human species. However, very little is known about the
      pathophysiology of the transplacental transmission of the virus from the mother
      to the fetus. In this study, the passage of CMV across the human term placenta,
      and the susceptibility of the human term trophoblast to infection with CMV was
      investigated. In vitro dual perfusion of human term placental lobules was
      performed. In five experiments the perfused tissue was exposed to high titres
      (10(4)-10(6) 50 per cent tissue culture infective doses) of CMV AD169 for up to
      9.5 h. Monitoring included placental functional parameters, and virus titres in
      the perfused tissue, and in the fetal and maternal circuit. Immunocytochemistry
      with a monoclonal antibody against CMV immediate early antigen was used to search
      for placental infection. CMV AD169 did not cross the placenta even during many
      hours of perfusion, up to 9.5 h, and with exposure to high virus titres. No
      infected placental cells were detected by immunocytochemistry, although the virus
      cultures from perfused tissue samples were positive. The perfused human term
      placenta and the term trophoblast in vitro form an effective barrier to cell-free
      CMV AD169.

PMID- 7567800
TI  - The effect of pre-eclampsia on human placental corticotrophin-releasing hormone
      content and processing.
AB  - Prior studies have shown that levels of corticotrophin-releasing hormone (CRH) in
      the umbilical cord blood of infants born after pregnancies complicated by pre
      eclampsia are significantly higher than fetal plasma CRH concentrations in
      uncomplicated pregnancies. In the present study we have measured CRH by
      radioimmunoassay in the placenta and fetal membranes from 13 pregnancies
      complicated by pre-eclampsia and compared them to 24 uncomplicated pregnancies.
      In addition we have investigated the effect of chronic intrauterine fetal stress
      on the processing of CRH in the placenta and fetal membranes. Placental CRH
      peptide content was significantly higher in the pregnancies complicated by pre
      eclampsia, 12,900 +/- 4230 pg/g tissue, than in the uncomplicated pregnancies,
      3130 +/- 430 pg/g of tissue (P < 0.01). Gel filtration of the homogenates of
      normal placenta revealed a major peak of CRH immunoactivity eluting in the same
      position as synthetic human CRH. A second smaller molecular weight peak of CRH
      immunoactivity was also present and in both the amnion and the chorion, the CRH
      eluted in the position of the smaller molecular weight peak. In contrast, the
      bulk of the CRH immunoactivity in the placenta and fetal membranes obtained after
      pregnancies complicated by pre-eclampsia eluted in the position of intact
      synthetic human CRH. Thus, in pregnancy complicated by pre-eclampsia, both
      placental CRH release into fetal plasma and CRH peptide content is higher than in
      uncomplicated pregnancy.

PMID- 7567801
TI  - Ferritin in cultured human cytotrophoblasts: synthesis and subunit distribution.
AB  - The present study aims at the role of ferritin in the regulation of
      syncytiotrophoblast free iron levels. The differentiated cytotrophoblast cell in
      culture is used as a model for this maternal-fetal interface. Cytotrophoblast
      cells isolated from term placentae are cultured in iron-poor (Medium 199), iron
      depleted [desferrioxamine(DFO)] and iron-supplemented [diferric transferrin (hTF
      2Fe), ferric ammonium citrate (FAC)] medium. Distribution and de novo synthesis
      of isoferritins is studied, together with the cellular iron concentration and the
      ferritin iron saturation. Compared to ferritin isolated from total placenta,
      ferritin obtained from villous tissue is enriched with acidic isoforms. This
      observation is in agreement with measured light (L) to heavy (H) subunit ratios <
      1 of de novo synthesized ferritin in cultured cytotrophoblast cells. Neither iron
      poor culture medium, nor hTf-2Fe supplemented medium affects the cellular iron or
      ferritin concentration. FAC increased the cellular ferritin iron saturation and
      (by synthesis) the acidic isoferritin concentrations. The results strongly
      suggest, that the term syncytiotrophoblast is able to balance transferrin
      mediated iron uptake and iron release. In case of FAC supplementation, the
      syncytiotrophoblast is unable to keep intracellular iron low, and ferritin
      synthesis is stimulated. The predominance of acidic ferritins and the
      preferential synthesis of H subunits can be functionally explained by the
      established fact that iron incorporation in acidic ferritins is faster due to the
      presence of ferroxidase centres. Damage by free iron catalysed hydroxyl radical
      formation is therefore minimized.

PMID- 7567802
TI  - Conference report: 1st international meeting of world placenta associations,
      Australia, 24-28 October 1994.

PMID- 7567803
TI  - Immunocytochemical localization of endometrial proteins.

PMID- 7567804
TI  - [Current perspectives in the treatment of epidermoid cancer of the esophagus].
AB  - Prior to the eighties, most patients with a diagnosis of epidermoid oesophageal
      cancer only received palliative symptomatic care. To date, most all undergo
      either surgery or medical treatment or both. Late diagnosis due to lack of
      clinical signs in the early phases of the disease, and perhaps insufficient
      attempts at identifying patients at risk who could benefit from systematic
      screening, is still an important problem although the number of diagnosed cases
      continues to rise (from 104 in 1985 to 151 in 1989 in Finistere in western
      France). Two different therapeutic attitudes could improve the prognosis:
      extensive surgery as proposed by the Japonese with dissection of all invaded
      lymph nodes whatever the localization and a multimodal approach combining
      radiochemotherapy and surgery. Although outcome can apparently be improved in
      certain types of oesophageal cancer, the proposal of aggressive extensive
      dissection could have an effect on respiratory complications and would not
      necessarily be adapted to the risk involved in western patients. Certain teams
      have nevertheless taken this route and will soon report their results. In France
      two phase II trials combining radiotherapy, chemotherapy (cisplatinum) and
      surgery have reported encouraging results with complete sterilization in 24% of
      the cases and 50% survival at 18 months. In our own series of 68 patients, we
      have obtained 41% sterilization and 56.3% survival at 3 years with the multi
      modal protocol. The high number of non-responders to chemotherapy emphasies the
      importance of maintaining surgical resection whenever possible. The discouraging
      reports published before 1980 have been contradicted by improvements in outcome
      achieved over the last decade. Today, all patients with a diagnosis of epidermoid
      cancer of the oesophagus should benefit from either palliative or curative care
      based on the latest advances in radiotherapy, chemotherapy and surgery.

PMID- 7567805
TI  - [Clinical and bacteriological aspects of nocardiasis. 9 cases].
AB  - OBJECTIVES: Nocardial infection is usually localized in the immunocompetent
      patient and occurs as an opportunistic disseminated infection in about half of
      the cases in immunoincompetents patients. METHODS: We report a retrospective
      assessment of 9 cases of nocardial infection diagnosed between January 1991 and
      February 1994. RESULTS: Six of the patients were immunodepressed: 3 had a
      disseminated infection with pulmonary (n = 2), brain (n = 2), skin (n = 3) and/or
      ocular (n = 1) localizations. There were 3 immunocompetent patients with an
      isolated local infection: skin and bone mycetoma, knee joint and lung. Diagnosis
      was made on samples obtained invasively in 7 patients. Nocardia asteroides was
      isolated in 5 patients, N. farcinica in 3 and N. caviae in 1. These organisms
      showed in vitro sensitivity to amoxicillin-clavulanic acid 5/9, cefotaxime 5/9
      (0/3 for N. farcinica), imipeneme 7/9, amikacin 8/8, minocyclin 5/8, pefloxacin
      0/8 and trimethoprime-sulfamethoxazol (TMP-SMX) 3/9. Clinical outcome was
      favourable in all cases and was not always correlated with laboratory
      sensitivity. CONCLUSION: TMP-SMX remains the reference antibiotic. For one
      patient, only TMP-SMX (resistant in vitro) was effective; with all the other
      antibiotic tried (sensitive in vivo) treatment failed.

PMID- 7567806
TI  - [Ethyl alcohol levels in the expiratory air vs blood alcohol levels. 204 cases in
      an emergency unit].
AB  - OBJECTIVES: Twenty to forty percent of all patients admitted to the emergency
      ward are positive for blood alcohol. Devices which measure alcohol in expired
      breath have been increasingly used in these units. This study was conducted to
      compare the results of breath alcohol analyzers with the classical laboratory
      methods based on enzyme assay and gas phase chromatography. METHODS: All patients
      with suspected acute ethanol intoxication at admission to the emergency room were
      included if blood alcohol had been ordered (enzyme assay and gas phase
      chromatography). RESULTS: There were 204 patients (151 men (74%) and 53 women
      (26%); mean age 43 +/- 12.7 years, range 14-80). The coefficient of correlation
      between blood alcohol level determined by gas phase chromatography (GC) and
      breath alcohol was 0.96 (r2 = 0.92, p < 10(-4)). The coefficient of correlation
      between breath alcohol and blood alcohol level determined by enzyme assay was
      0.96 (r2 = 0.92, p < 10(-4)). Comparing the coefficients of correlation GC/blood
      (r2 = 0.92) versus GC/enzyme assay (r2 = 0.96) demonstrated a statistically
      significant difference (p < 10(-3)). CONCLUSION: In our 204 patients, the breath
      alcohol analyzer gave 3 false positives and 3 false negatives (2.94%). Even
      though breath alcohol levels are 21.1% lower than the levels given by gas phase
      chromatography, it is an instantaneous nonaggressive method well correlated with
      classical blood tests. Nevertheless, this method could not be used in 19.6% of
      emergency patients due to physical impossibility or refusal, justifying
      laboratory tests.

PMID- 7567807
TI  - [Beta-2 microglobulin in cerebrospinal fluid in neurology].
AB  - OBJECTIVES: beta 2-microglobulin (beta 2-m) is a small molecular weight protein
      (11 800 Daltons) which can transudate into the cerebrospinal fluid (CSF) in the
      same manner than albumin. Intrathecal synthesis is a sign of local immuno
      stimulation and is correlated with immunoglobulin G. The aim of this study was to
      ascertain the relationship between beta 2-microglobulin levels in the CSF and
      neurological diseases. METHODS: beta 2-microglobulin was assayed in the CSF and
      blood using an immunoenzyme method in 64 patients with multiple sclerosis (n =
      14), human immunodeficiency virus (HIV) infection (n = 5), meningitis (n = 12) or
      a peripheral neurological disease (n = 10) and in 7 control subjects. RESULTS:
      There was no overall correlation between beta 2-m in the CSF and blood levels (r
      = 0.35). In controls, beta 2-m CSF and blood levels were respectively 0.94 +/-
      0.22 and 1.46 +/- 0.83 mg/l. beta 2-m was significantly higher in the CSF of
      patients with meningitis and in the HIV positive patients (4 +/- 3.5 and 3.69 +/-
      2.06 mg/l respectively) (p < 0.05). Type of meningitis (bacterial or non
      bacterial) had no effect on the CSF level. For the HIV patients, the CSF/blood
      ratio for beta 2-m was similar to that in controls due to a rise in both blood
      and CSF. Finally, in patients with multiple sclerosis, there was no significant
      change in CSF level of beta 2-m. CONCLUSION: beta 2-microglobulin in
      cerebrospinal fluid was not found to be correlated with the neurological diseases
      studied and cannot be used as a diagnostic test.

PMID- 7567811
TI  - [Escherichia coli O157:H7. A case of hemolytic uremic syndrome].

PMID- 7567812
TI  - [Pasteurella multocida meningitis in the adult].

PMID- 7567810
TI  - [Lymphomatoid papulosis].
AB  - Lymphomatoid papulosis is a distinct entity in which recurring crops of
      haemorragic and necrotic papules display a cytologically malignant infiltrate.
      The aberrent cell is now generally accepted to be an active T helper phenotype.
      The expression of Ki-1 (CD30) on a significant portion of the infiltrating cells
      characterizes lymphomatoid papulosis and relates this disorder with Hodgkin's
      disease, mycosis fungoides and anaplasic T cell lymphoma which may be associated
      in 10 to 20% of lymphomatoid papulosis. The categorization of this disease as a
      benign disorder versus lymphoma remains controversial. Studies of T cell receptor
      gene rearrangement demonstrate clonality in many cases. So, this monoclonal
      population could have a malignant transformation induced by a triggering stimulus
      such as genetic translocation, or viral infection. Finally, recent opinions
      consider that lymphomatoid papulosis and Ki-1 (CD30) lymphomas are different
      parts of a clinical and histological spectrum constituted by cutaneous Ki-1
      lymphoid infiltrates.

PMID- 7567813
TI  - [An original treatment of Ogilvie syndrome: the nicotine patch].

PMID- 7567808
TI  - [Repeated studies of the prevalence of Staphylococcus aureus in the nasal cavity
      in hemodialysed patients].
AB  - OBJECTIVES: In order to better establish a prevention strategy based on
      mupirocin, we evaluated nasal carriage of Staphylococcus aureus in haemodialysis
      patients over a 15 month period. METHODS: Search for Staphylococcus aureus in the
      nasal cavities was made every 2 months in 92 chronic dialysis patients. These
      patients were divided into 3 groups according to the nature of the carriage: non
      permanent, intermittent or permanent. RESULTS: Among the 80 patients retained for
      analysis, there were 27.5% with intermittent carriage and 11.25% with permanent
      carriage. Factors which appeared to protect against carriage were rural residence
      and home self-dialysis. CONCLUSION: Repeated long-term search for nasal carriage
      of Staphylococcus aureus has provided reliable data for each patient and gave
      information on the effects of epidemiological conditions and health care
      structures.

PMID- 7567809
TI  - [New techniques in thoracic surgery. I].
AB  - Progress over the last 40 years has greatly reduced morbidity and mortality in
      the constantly changing field of thoracic surgery. The first part of this review
      focuses on current indications and limitations in lung surgery. Technical
      procedures for pneumonectomy, lobectomy, bronchial resection and conservative
      surgery are well established. Although major respiratory or cardiac failure still
      limit indications bronchogenic cancer extension is no longer a contraindication.
      Exeresis after 70 years of age is not an exception. Surgery for non-small cell
      lung cancer has given promising results with a 5-year survival rate of 60-80% for
      patients in stage I and II. For stage III, two recent comparative studies have
      demonstrated the effectiveness of preoperative adjuvant chemotherapy which should
      logically be proposed with or without radiotherapy in patients with resectable
      tumours. Surgical removal of lung metastases and mesotheliomas has also made
      considerable progress. Unfortunately, except for therapeutic trials, exeresis of
      small cell lung cancer does not provide any beneficial effect and cannot be
      proposed. Indications for surgery in patients with chronic obstructive pulmonary
      disease however has been quite successful and now goes beyond classical exeresis
      of large compressive bullae. In many situations patients with diffuse emphysema
      can benefit from surgical reduction in lung volume before proposing
      transplantation. Lung transplantation is indicated for pulmonary fibrosis,
      pulmonary vascular disease and obstructive lung pulmonary disease with an overall
      survival rate of 50% at 5 years and 43% at 6 years. The rate of successful
      bilateral lung transplantation for cystic fibrosis remains to be determined.

PMID- 7567814
TI  - [Meningitis, septicemia and endophthalmitis caused by Streptococcus equi
      subspecies zooepidemicus].

PMID- 7567816
TI  - [Liver transplantation: the necessary evaluation, the indispensable
      organization].

PMID- 7567815
TI  - [Annual incidence of IgA nephropathy (Berger syndrome) in France].

PMID- 7567820
TI  - [Characteristics of chronic headaches after whiplash injury].
AB  - OBJECTIVES: The aim of this study was to identify the characteristics of post
      traumatic headache after whiplash injury in order to obtain some indications as
      to the pathogenesis of this particularly frequent clinical entity. METHODS: A
      retrospective study of 63 patients who had suffered whiplash injury and who had
      persistent chronic pain was conducted. RESULTS: Forty-seven patients complained
      of headache and pain in the cervical spine and 16 of pain in the cervical spine
      alone. Among the patients with headache 74% complained of tension-like pain,
      while only about 10% had identifiable post-trauma migraine headache with or
      without aura. Current neurophysiological hypotheses of central dysfunction due to
      neurochemical disorders induced by the initial nociceptive stimuli, frequently
      found in the general population, would not explain the disabling characteristics
      observed in these patients with chronic pain. CONCLUSION: A multifactorial
      pathogenesis of post-traumatic chronic headache should be entertained, suggesting
      that not only trauma but also extra-trauma factors unrelated to whiplash would be
      involved.

PMID- 7567819
TI  - [Induced expectoration: its role in the diagnosis of pneumocystis carinii
      pneumonia].
AB  - OBJECTIVES: The purpose of this retrospective study was to describe the changes
      and the effect of Pneumocystis carinii pneumonia (PCP) prophylaxis on induced
      sputum sensitivity during these five last years METHODS: An induced sputum
      examination was performed in 80 cases of PCP over a 5-year period. RESULTS: The
      induced sputum were positive in 30 cases (sensitivity = 37.5%). This sensitivity
      changed very little during these five years. Thirty of these 80 patients (37.5%)
      received PCP prophylaxis at least for four weeks before PCP diagnosis. Induced
      sputum sensitivity was 50% in the group with prophylaxis versus 30% in the group
      without prophylaxis (p = 0.073). CONCLUSION: In our institution, the induced
      sputum examination remains an interesting diagnostic procedure for PCP. PCP
      prophylaxis does not seem to have effects on induced sputum sensitivity.

PMID- 7567821
TI  - [Revascularization of supra-aortic trunks from the femoral artery].
AB  - A seventy-year-old woman had an occlusion of the left sub-clavian and left
      primitive, internal and external carotid arteries, combined with a pre-thrombotic
      stenosis of the brachiocephalic trunk. Lesions were so diffused that a cross
      extra-anatomic bypass was impossible at the cervical level. There was
      contraindication for the implantation of a prosthesis on the aortic arch, due to
      a much extended calcified atheroma which did not allow clamping. Supra-aortic
      trunk revascularization was done through right femoral-axillary bypass without
      any post-operative complication. After a four year follow-up, the bypass is still
      patent. The purpose of this report is to emphasize that such r revascularization,
      which is rarely reported, must be better known since the implantation of the
      bypass on the femoral artery leads to patent and durable results.

PMID- 7567822
TI  - [New techniques in thoracic surgery. II].
AB  - The surgical approach to affections of the chest wall and pleura, still the
      predominant indications for thoracic surgery, has greatly changed since the
      advent of thoracoscopic procedures, and is emphasized in this second part of a
      two-part review, together with other indications for mediastinal tumours.
      Indicated after lung exeresis or emergency chest surgery, protective chest wall
      reconstruction with muscular flaps is no longer an exceptional operation.
      Inversely, thoracic surgery for infectious complications have become less
      frequent, unusually limited to well established procedures for tuberculosis
      surgery, treatment of bronchial fistula or mediastinal supperations. The chest
      cavity is well adapted to new techniques of thoracoscopy and video-assisted
      thoracic surgery both for diagnosis and treatment. Indications for pleuroscopy
      have taken on a completely new aspect since 1989. These techniques are used for
      pericardial fenestration, thoracic sympathectomy for dyshidrosis, vagotomy,
      splanchnicectomy, chylothorax, spinal affections, empyema and trauma surgery.
      These new techniques have also had an impact on treatment of spontaneous
      pneumothorax. For tumour surgery, thoracoscopy has made possible a more adapted
      strategy currently based on an initial needle biopsy, with limited thoracoscopic
      exeresis and ultimate treatment depending upon the pathology report. Immediate
      thoracoscopy without prior biopsy appears excessive. Video-assisted
      thoracosurgery is also used for most malignant mediastinal tumour which, due to
      advances in chemotherapy surgery have transformed the prognosis of a large number
      of mediastinal tumours.

PMID- 7567818
TI  - [Study of oxidative stress in the elderly].
AB  - OBJECTIVES: Determine the oxidative stress status and its significance in elderly
      subjects. METHODS: Six parameters marking oxidative stress evaluated in 52
      elderly patients (mean age 85 +/- 6 years; range 74 to 98) admitted to a medium
      term and long-term nursing home (n = 30) or a hospital ward (n = 22) were
      compared with those in 30 disease-free young subjects (age range 20-40 years).
      Plasma levels of thiobarbituric acid reactive substances vitamin E and selenium
      and activity of free-radical protective enzymes (erythrocyte superoxide
      dismutase, plasma and erythrocyte glutathione peroxidase) were assessed. RESULTS:
      Thiobarbituric acid reactive substances were higher and superoxide dismutase,
      erythrocyte and plasma glutathione peroxidase, and plasma selenium were lower in
      elderly patients than in young controls. There was no difference in vitamin E
      levels. In the nursing home population, erythrocyte superoxide dismutase was
      correlated with erythrocyte glutathione peroxidase and vitamin E, plasma
      glutathione peroxidase with erythrocyte glutathione peroxidase, vitamin E and
      selenium and erythrocyte g peroxidase, vitamin E and selenium and erythrocyte
      glutathione peroxidase with vitamin E. Only the correlation between erythrocyte
      and plasma glutathione peroxidase was found in the hospitalized population. These
      levels remained unchanged for a 30 day period in individual patients. CONCLUSION:
      "Oxidative stress" assessed by six parameters was thus observed in the elderly
      population and could be considered as a "biological marker of ageing".
      Supplementation with selenium or other anti-oxidants could be proposed.

PMID- 7567824
TI  - [Is the incidence of testicular cancer on the increase in France?].

PMID- 7567817
TI  - [Evaluation of results of liver transplantation: experience based on a series of
      1052 transplantations].
AB  - OBJECTIVES: The aim of this work was to evaluate outcome in a continuous
      homogeneous series of more than 1000 liver transplantations in order to determine
      risk groups. METHODS: Between November 1984 and February 1995, 1052 isolated
      orthotopic liver transplantations were performed in 922 patients (530 males, 392
      females; mean age 41.7 years; age range 10 months - 78 years) at the Paul-Brousse
      Hospital liver transplantation unit. Immunosuppression was based on cyclosporin
      in all patients with FK506 in the most recent cases. RESULTS: Actuarial survival
      at 1,5 and 8 years for the 922 patients was 80.9, 71.7, and 69.1%. Certain
      factors affecting the intrinsic risk of transplantation were identified and could
      be used to calculate supplementary risk due to one or more other risk factors. In
      adults under 55 years in UNOS stage 1 or 2 (not hospitalized at call in)
      transplanted after 1990 for non-recurrent (absence of cancer, non-viral disease)
      chronic liver disease, the risk of death at 1 year was 6.5% and 4.4% between the
      first and second year. For patients transplanted for acute liver failure and for
      patients transplanted for chronic liver disease in UNOS stade 3 or 4
      (hospitalized or in an intensive care unit at call in), there was a supplementary
      risk of death at 1 year of 20.3%, 13.3% and 31.6% respectively. There was no
      supplementary risk of death in these three groups after 1 year. In patients over
      55 years, there was a 4.4% supplementary risk during the first year after
      transplantation and a 2% increase between the first and second year. In patients
      transplanted for cancer, the supplementary risk was 9.7% during the first year,
      11.6% between the first and second year and 2.1% between the third and fifth
      year. CONCLUSIONS: On the basis of these results, it was possible to develop a
      method for assessing liver transplantation outcome in different units. The
      proposed criteria is the 1 year survival of patients with the basic risk alone,
      without any supplementary risk, as well as the retransplantation index (mean
      number of grafts used per patient). For the Paul-Brousse unit, this criteria is
      93.5% (survival at 1 year) for a retransplantation index of 1.1.

PMID- 7567823
TI  - [Anterior pituitary failure in the post-partum period and autoimmune thyroiditis:
      pituitary necrosis or hypophysitis?].

PMID- 7567825
TI  - [Cyclospora infection in a HIV infected patient].

PMID- 7567827
TI  - [Brain abscess caused by Salmonella enteriditis associated with brain tumor].

PMID- 7567826
TI  - [Premenopausal hyperprolactinemia revealing pseudotumoral hypophysitis].

PMID- 7567828
TI  - [Endocarditis caused by Corynebacterium diphtheriae tolerant to amoxicillin].

PMID- 7567829
TI  - [Management of dyslipidemia].
AB  - There is now an enormous amount of literature on the relationship between blood
      lipids and coronary artery disease. It is clear that the treatment by
      modification of the diet and hypolipidaemic drugs is associated with a decrease
      of the coronary events. However there is no cure for any of the primary
      dyslipidemias and relative treatment involves a life-long commitment by the
      patient. In addition the efficiency of the treatment is dramatically different in
      patients at very high risk (secondary prevention, combination of several risk
      factors) and in those at moderate risk. Furthermore, patient's compliance is
      usually low. Therefore management of the hyperlipidaemic patients requires a
      rigorous approach to evaluate the global risk and consequently to adapt the
      treatment at an individual level. We describe here our outpatient clinic in which
      about 6000 hyperlipidaemic patients have been referred. We indicate the strategy
      that we used for taking care the patients including 1) the education of the
      subjects 2) the detection of secondary hyperlipidaemia 3) the evaluation of the
      global risk including non-invasive evaluation of the atherosclerosis and the
      results of such approach (for example, we found a much higher percentage of
      positive exercise ECG in patients with carotid atherosclerosis in our
      ultrasonographic examinations.

PMID- 7567830
TI  - [Dysfunction of the upper respiratory airways in patients with essential tremor].
AB  - OBJECTIVES: To investigate pulmonary function abnormalities in essential tremor.
      METHODS: We obtained maximal inspiratory and expiratory flow-volume curves in 41
      unselected patients with essential tremor (14 males, 27 females, age 61.7 +/-
      2.14 years). Severity of essential tremor was evaluated using the Fahn, Tolosa
      and Marin clinical scale. RESULTS: Sixteen patients (39.0%) had flow oscillations
      on the flow-volume curves (8 only during inspiration, 7 during inspiration and
      expiration, and 1 with flow oscillations during inspiration and obstructive
      pattern). The duration and severity of the essential tremor did not influence the
      pattern of the curve, but abnormal curves were more frequent in patients with
      voice tremor. Although there were a number of significant correlations between
      essential tremor scales and spirographic parameters, they were of very low range.
      Four patients (9.8%) fulfilled criteria for physiological upper airway
      obstruction: 2 had smooth flow-volume loop contour and 2 had flow oscillations in
      inspiration and expiration. CONCLUSION: Abnormalities in flow-volume loop contour
      are a usual finding in essential tremor. This probably reflects involvement of
      the upper airway musculature, that in some patients can produce clinical upper
      airway obstruction.

PMID- 7567831
TI  - [Mycobacterium gordonae infections in human immunodeficiency virus infection].
AB  - OBJECTIVES: Non-tuberculous mycobacteria infections are frequent in patients
      infected with the human immunodeficiency virus (HIV). Mycobacterium avium
      intracellulare is the most frequent organism isolated but several other
      mycobacteria are also seen. Mycobacterium gordonae is a saprophytic mycobacteria
      which is rarely pathogenic. It was observed in 9% (7 patients) of the
      mycobacterial infections observed in our unit over a period of 3 years. METHODS:
      In order to determine whether M. gordonae plays a pathogenic role in HIV-infected
      patients, we re-evaluated the 7 clinical files of patients with M. gordonae
      infection. The findings were compared with data in the literature. RESULTS: All
      seven of our patients had a poor general health status with fever and pulmonary
      infection. The chest X-ray was abnormal in 5 patients. M. gordonae was isolated
      from blood cultures in 2 patients and from sputum or gastric contents in 5.
      Outcome was favourable using anti-tuberculosis combinations. CONCLUSION: A
      pathogenic role for M. gordonae cannot be excluded in HIV-infected patients.
      However, since this mycobacterium is an ubiquitous organism, diagnosis should be
      based on a typical clinical presentation and certain laboratory identification
      from appropriate samples.

PMID- 7567832
TI  - [Value of celioscopy in the diagnosis of inguinal hernia].
AB  - OBJECTIVE: Prospectively compare laparoscopic findings with functional impairment
      and clinical diagnosis and classification of inguinal hernias. METHODS: Fifty
      eight consecutive patients (mean age 55.3 years, range 22-87) presenting with 68
      symptomatic hernial orifices and undergoing laparoscopic procedures for inguinal
      hernia were included in the study. Type of hernia was identified according to the
      Nyhus classification. Clinical examination found 73 hernias and laparoscopy
      identified 86 hernias. RESULTS: Laparoscopic findings confirmed clinical
      diagnosis in 20 out of 30 type II hernias, 24 out of 37 type IIIA hernias, 2 out
      of 3 type IIIB hernias and 13 out of 16 type IV hernias. CONCLUSION: Laparoscopic
      procedures can successfully confirm or refute the clinical diagnosis of inguinal
      hernia, especially important when the preoperative diagnosis is doubtful. The
      type of hernia can be clearly identified for adaptation of therapeutic
      indications.

PMID- 7567833
TI  - [Pseudomonas aeruginosa septicemia. Host-related risk factors in 82 episodes].
AB  - OBJECTIVES: The prognosis of septicaemia due to Pseudomonas aeruginosa is severe
      with mortality ranging from 32 to 73%. We retrospectively studied 82 episodes in
      order to determine whether risk factors could be identified. METHODS: Eighty-two
      episodes of Pseudomonas aeruginosa septicaemia, observed between 1986 and 1991,
      were analyzed. Risk of death within 2 days of the first positive blood culture
      (mortality = 19.5%) were assessed with univariate and multivariate analyses.
      RESULTS: Patient age ranged from 1 to 92 years. Most had been hospitalized in
      medical wards (49%) or intensive care units (28%) (NS). The type of septicaemia
      (several bacteria in 21%), the source of the infection (nosocomial in 78%),
      portal, predisposing factors (cancer, haematologic disease: 54%) and MacCabe
      index were not significantly correlated with risk of death at two days following
      first positive blood culture. With univariate analysis body temperature below
      38,5 degrees C was significant (p = 0.007) for death at day 2 and appropriate
      antibiotic treatment after diagnosis was significant (p < 0.001) for absence of
      death on day 2. For multivariate analysis, chemotherapy and shock syndrome were
      significant (p = 0.005 and 0.09 respectively) for death at day 2 and appropriate
      antibiotic treatment was significant (p = 0.005) for absence of death on day 2.
      CONCLUSION: Antibiotic prescription appears to be the most easily controlled
      significant factor predictive of outcome in Pseudomonas aeruginosa septicaemia.

PMID- 7567834
TI  - [Breast cancer after preventive subcutaneous mastectomy].
AB  - Because of a family history of breast cancer, a 51-year-old patient underwent
      bilateral subcutaneous mammectomy in 1988. In February 1994 she presented with a
      nodule in the supramedial quadrant on the left. Needle biopsy suggested
      galactophoric adenocarcinoma which was confirmed histologically. A 1.5 cm tumour
      was removed together with a 3 cm reliquat of glandular tissue. Twelve axillary
      nodes were dissected and were found to be free of neoplastic infiltration.
      Hormone receptors were positive. Post-operative radiotherapy was performed. The
      outcome is unchanged at 6 months. Bilateral subcutaneous mammectomy can be
      proposed as a preventive measure in patients at risk, but as demonstrated by this
      case, exeresis is usually incomplete. The level of protection actually achieved
      is thus questionable. Clinicians should be aware of the risk of breast cancer
      developing after such elective operations since early screening programmes and
      the development of genetic methods based on the search for BRCA1 and BRCA2 genes
      will undoubtedly increase the number of patients requesting preventive measures.

PMID- 7567839
TI  - [Bronchial fibroscopy through the laryngeal mask in patients with chronic
      respiratory insufficiency].

PMID- 7567836
TI  - [Superantigens and their implication in autoimmune diseases].
AB  - Superantigens, unlike conventional antigens, are capable of stimulating cell
      growth and differentiation of a large proportion of T cells (10 -40%). There are
      two types of superantigens: endogenous retroviral superantigens (described only
      in mice) and bacterial superantigens. Bacterial superantigens are heat-resistant
      enterotoxins responsible for Staphylococcus food poisoning or toxic shock
      syndromes. T lymphocyte proliferation is associated with production of large
      quantities of cytokines, including interleukin-1, 2, 4, 6 and tumour necrosis
      factor which induce the symptoms observed in toxic syndromes. These superantigens
      form trimolecular complexes with the beta chains on the outer peptide pouch of
      class II HLA molecules and with certain families of V beta chains of the T-cell
      receptors on CD4 and CD8 lymphocytes. Unlike conventional antigens, superantigens
      do not have to be processed in small-sized peptides before presentation to T-cell
      receptors by the class II HLA molecules. The late consequences of T-cell
      activation by superantigens are either a deletion of the T-lymphocytes carrying V
      beta chains in families specific for a superantigen, or an anergy. The
      oligoclonal characteristic of T-lymphoid populations infiltrating the central
      nervous system, the synovial membrane or the salivary glands suggests that
      superantigens are implicated in the pathogenesis of certain autoimmune diseases
      such as multiple sclerosis, rheumatoid arthritis, and Sjogren's syndrome. Certain
      Staphylococcus superantigens could be the cause of Kawasaki's syndrome.

PMID- 7567835
TI  - [Intra-alveolar hemorrhage. An uncommon accident in a breath holding diver].
AB  - To date, pulmonary oedema in breath hold divers has only been reported after
      dives below 50 meters, hypoxaemic syncope being the most common risk. We recently
      observed a 35-year-old well-trained breath hold diver who was unable to achieve
      deep inspiration during a high-level competition. After two hours of repeated
      dives to a depth of 25 meters for approximately 2-minute periods with
      intermittent recovery the patient developed cough and haemoptysis. The chest X
      ray revealed lung images suggestive of intra-alveolar haemorrhage. The patient
      had taken 1 g of aspirin per os for three days prior to diving. Symptoms subsided
      spontaneously in 48 hours and one month later all haematology tests were normal
      except for minimal alteration of platelet aggregation. Pulmonary oedema in breath
      hold divers is usually attributed to blood shift to the pulmonary circulation
      related to the lowered intra-thoracic pressure. In our case, oedema was secondary
      to intra-alveolar haemorrhage favoured by aspirin which should be avoided before
      breath hold diving.

PMID- 7567840
TI  - [Intraventricular arrhythmia after propoxyphene poisoning].

PMID- 7567838
TI  - [Tumor lysis syndrome in chronic lymphoid leukemia treated with chlorambucil and
      prednisone].

PMID- 7567837
TI  - [Myasthenia during interferon alpha therapy].

PMID- 7567842
TI  - Nosocomial infection by Alcaligenes xylosoxidans in neutropenic patients.

PMID- 7567844
TI  - [Consensus, competence, consequences in the art of surgery].

PMID- 7567841
TI  - [B lymphoma with abundance in T-cells disclosed by sciatic nerve pain and
      hypercalcemia in the absence of bone lesion].

PMID- 7567843
TI  - [International Herpes Virus Management Forum 1994].

PMID- 7567846
TI  - [Nocturnal hypoglycemia in insulin-dependent diabetics].
AB  - OBJECTIVES: Repeated hypoglycaemia has been reported to impair recognition of
      subsequent hypoglycaemia with a high risk of severe hypoglycaemia. This
      intensified insulin therapy may be dangerous in insulin-dependent diabetes
      mellitus (IDDM) patients with unawareness of hypoglycaemia. METHODS: We assessed
      the incidence of nocturnal hypoglycaemia and the benefit of an additional bedtime
      snack in IDDM patients treated by 2 or 3 daily injections. Capillary blood
      glucose was measured by finger strip at 10 p.m. and plasma venous glycaemia was
      determined at 0, 2, 4 and 8 a.m. RESULTS: The study was composed of two phases.
      In the first phase, patients (n = 93) did not receive any snack at bedtime. Blood
      glucose fell to 2.75 mmol/l or less in 33%. Among the 40 patients with a 10 p.m.
      glycaemia of 9 mmol/l or less, 57.5% experienced nocturnal hypoglycaemia vs 15%
      of the 53 others. The second phase concerned 106 IDD patients. An additional
      bedtime snack was given when 10 p.m. blood glucose was 9 mmol/l or less. The
      incidence of hypoglycaemia fell to 32% (14 of 44 IDDM) i.e. a significant benefit
      of 44% (p < 0.01). However patients who received this additional bedtime snack
      had a slightly higher 8 a.m. glycaemia than those with 10 p.m. glycaemia at 9
      mmol/l or less during the first phase (9.61 +/- 5.67 mmol/l vs 7.75 +/- 4.30
      mmol/l) but this result is not significant. CONCLUSION: Prevention of nocturnal
      hypoglycaemia may be achieved in IDDM patients by bedtime glucose determination
      and an additional snack when glycaemia is 9 mmol/l or less.

PMID- 7567845
TI  - [Preimplantation diagnosis of delta F508 mutation of mucoviscidosis in transgenic
      mice].
AB  - OBJECTIVE: The aim of our study was to master preimplantation diagnosis in
      transgenic mice. METHODS: Stage 4 or 8 cells preembryos were collected from
      C57BL6xCBAF1 mice, three days after mating with transgenic C57BL6xSJLF1 mice
      homozygous for the human gene delta F508 mutation of cystic fibrosis. A single
      blastomere was sampled by microbiopsy and the preembryos transferred in Swiss
      mice foster mothers. Molecular biology for delta F508 mutation on a single
      blastomere was performed with a double PCR technique on a Perkin Elmer Cetus
      9600. RESULTS: The success rate of biopsy on the 122 preembryos with 4 cells was
      90.2%, and 93.8% on the 128 prembryos with 8 cells. The rate of in vitro hatching
      was 84.6% after biopsy on 52 preembryos with 4 cells (92.2% for controls without
      biopsy, p > 0.05), and 90.0% for 50 preembryos with 8 cells (94.4% for controls
      without biopsy, p > 0.05). The rate of birth after biopsy and transfer of 42
      preembryos with 4 cells was 66.7% (72.5% for controls transferred without biopsy,
      p > 0.05) and 70.3% for 37 preembryos with 8 cells (71.9% for controls, p >
      0.05). No difference was evidenced for births weight or organ weight at 3 weeks
      between mice born from biopsied embryos and controls. Thirty-two double PCR were
      performed for the diagnosis of the cystic fibrosis delta F508 mutation, 20 on a
      single blastomere obtained by microbiopsy and 12 for various negative controls,
      with 100% specificity and 100% sensitivity. CONCLUSIONS: Microbiopsy of
      preembryos with 4 cells or 8 cells does not alter their viability or further
      development. The double PCR technique on a single blastomere for the cystic
      fibrosis delta F508 mutation is reliable with our current methods of
      investigation.

PMID- 7567847
TI  - [Treatment of chronic hepatitis C with lymphoblastic interferon. Long-term follow
      up].
AB  - OBJECTIVES: A randomized controlled trial was set up to assess the effect of two
      different therapy regimens with lymphoblastoid interferon on the treatment and
      follow-up of patients with chronic C hepatitis. METHODS: Eighty-five patients
      with chronic hepatitis C were randomized into two treatment groups (n = 30
      respectively) and one control group (no treatment: n = 25). In one treatment
      group patients received three million units of alpha-lymphoblastoid interferon.
      The other received six million units. RESULTS: A rapid decline in both alanine
      aminotransferase and aspartataminotransferase levels was seen in most treated
      patients (a complete response in 51% from group A and 55% from group B; partial
      response 29% from group A, 25% from group B). In five partial responders and six
      complete responders from group A and in seven partial responders and six complete
      responders in group B serum aminotransferase levels returned to baseline values
      in the follow-up. No change in serum bilirubin, albumin, IgG and prothrombin time
      during interferon treatment were seen. The histologic staging remained unchanged
      throughout the entire study. CONCLUSION: alpha-interferon treatment improves the
      clinical picture, biochemical parameters and histologic pattern in a large
      percentage of patients with hepatitis C. Long-term remission was seen in only 37%
      of treated patients. Using six million units of alpha-interferon has not proven
      to be significantly better than three million units. Protracted treatment for
      nine months seems to increase the percentage of patients in biochemical and
      histologic remission.

PMID- 7567848
TI  - Adult onset Still's disease. 16 cases.

PMID- 7567849
TI  - [Acute Budd-Chiari syndrome of traumatic origin].
AB  - The diagnosis of Budd-Chiari syndrome is based on clinical signs including liver
      enlargement and ascitis and findings of complementary examinations: echography,
      echo-Doppler, CT-scan, magnetic resonance imaging, angiography, pressure
      readings, laparoscopy and biopsy. Trauma is rarely reported as a cause of acute
      Budd-Chiari syndrome. In some cases, the trauma is so violent the supra-hepatic
      veins are ruptured and the dramatic outcome leaves no time for the syndrome to
      develop. In others, the resulting haematomas form a compression block of the
      suprahepatic vessels. The mechanism of the trauma in our case appears to have
      been unreported to date. Four days after a violent motorcycle accident, a 33-year
      old man developed an acute Budd-Chiari syndrome probably due to partial and
      temporary thrombosis of the left and middle suprahepatic veins. A side-to-side
      porto-cava anastomosis with a calibrated venous graft was performed in an
      emergency procedure. Outcome was quite favourable and after a 4 year follow-up,
      the patient is in good health.

PMID- 7567850
TI  - [Hyperimmunoglobulin D syndrome].
AB  - The hyper-IgD syndrome is a rare entity characterized by early onset of attacks
      of periodic fever. All patients have an elevated serum IgD (> 100 U/ml). Symptoms
      during attacks include joint involvements (arthralgias/arthritis), abdominal
      complaints (vomiting, pain, diarrhoea), skin lesions, swollen lymph nodes, and
      headache. In 1992 an International hyper-IgD study group was established, and to
      date the diagnosis has been made in 60, mainly European patients; 14 come from
      France. The disorder occurs in families and is transmitted by autosomal recessive
      inheritance. Linkage studies indicate that the gene encoding for familial
      Mediterranean fever is different from the gene for the hyper-IgD syndrome. In
      children the hyper-IgD syndrome should be distinguished from two other periodic
      febrile disorders. CINCA (chronic inflammatory, neurological, cutaneous and
      articular syndrome) and FAPA (periodic fever, adenopathies, pharyngitis, and
      aphtous stomatitis) share some symptoms with the hyper-IgD syndrome but in these
      syndromes serum IgD is normal. The pathogenesis remains to be elucidated but
      during attacks all patients have an acute-phase response with elevated C-reactive
      protein concentrations. During the febrile episodes, the inflammatory cytokines
      such as IL-6 TNF alpha, IFN gamma are increased together with natural occurring
      inhibitors such as IL-1ra and sTNFr. There is no therapy for the syndrome and
      patients will experience attacks during their entire life although frequency and
      severity tend to diminish with age.

PMID- 7567851
TI  - [Chemotherapy of metastatic soft tissue sarcoma].
AB  - The chemosensitivity of bone sarcomas contrasts sharply with the comparative
      initial chemoresistance of soft tissue sarcomas. The lack of new effective
      cytotoxic agents, delayed treatment due to a clinical presentation which is often
      innocuous and the absence of a consensus about the role of adjuvant chemotherapy
      after adequate surgery account for the slow progress achieved in the treatment of
      these tumours and for such an appalling prognosis. Chemotherapy is still purely
      palliative except for certain specific metastatic lesions, and median overall
      survival is more often than not below 12 months. However, the optimization of the
      therapeutic index of the most active antimitotic drugs, the ever-increasing
      acceptance of the concept of a dose-effect for the majority of these lesions, the
      particularly promising objective response rates with intensive drug combinations
      and a better understanding of the development process of certain lesions and
      histologic subtypes make it possible to envisage a rapid improvement in their
      still far too dismal prognosis.

PMID- 7567852
TI  - [Erythema nodosum disclosing chronic active hepatitis C].

PMID- 7567854
TI  - [IgAk solitary bone plasmacytoma leading to the loss of heavy chain alpha].

PMID- 7567853
TI  - [Reactivation of hepatitis B in AIDS].

PMID- 7567855
TI  - [Myxoma of the left atrium disclosed by femoral embolism. Value of anatomo
      pathological study of the vascular desobstruction product].

PMID- 7567856
TI  - [p6sional pulmonary edema after transfusion of leukocyte-free erythrocyte
      concentrates].

PMID- 7567857
TI  - [Acute kidney failure after a tam-tam concert].

PMID- 7567858
TI  - [Tuberculin-BCG therapy in combined treatment of patients with pulmonary
      tuberculosis].
AB  - The efficacy of combined use of tuberculin and BCG vaccine (tuberculin-BCG
      therapy) given to 70 patients with new-onset and recurrent pulmonary tuberculosis
      was compared to that of BCG treatment only received by 24 patients. Bacterial
      discharge and caverns were registered in 80 and 78 patients, respectively. 25
      patients underwent stimulating, 37, 8 paradoxical tuberculin-BCG-therapy. BCG
      vaccine (1-4 injections) was given 2 weeks after the course of individual
      tuberculin therapy with the low efficacy of the latter. Tuberculin-BCG-therapy
      produced marked response in 52 patients against 11 responses on BCG only,
      increased the number of T-lymphocytes and T-helpers. It is concluded that the
      above combination improves regulation of an immune response by cellular
      mechanisms.

PMID- 7567859
TI  - [Immunological and nonspecific reactivity in patients with infiltrative pulmonary
      tuberculosis associated with chronic nonspecific lung diseases].
AB  - When examined for immunological status, complement, basic endogenic protease
      blockers parameters, patients with infiltrative destructive tuberculosis of the
      lungs (IDTL) and IDTL combination with exacerbation of chronic pyo-inflammatory
      bronchitis, exhibited disturbances in cellular and humoral immunity, complement
      activity, content of alpha 1 protease inhibitor and alpha 2 macroglobulin which
      aggravated in combined respiratory pathology. Nonspecific aerosol treatment with
      native protease inhibitors (contrykal or gordox) and thymalin aroused the
      efficacy of etiotropic treatment and promoted normalization of the above defense
      systems.

PMID- 7567860
TI  - [Immunological and hematological criteria of the prognostication of the
      effectiveness of tuberculosis chemoprophylaxis in children].
AB  - Immunological indices and hemograms were studied in 80 children early in the
      course of primary tuberculous infection to ascertain prognostic criteria of
      chemoprophylaxis efficacy. Of prognostic importance appeared: to be the Mantoux
      test with 2 TU PPD-L; T-lymphocyte, T-helpers, active T-lymphocytes, leukocyte,
      eosinophil count; leukocyte migration inhibition test with pulmonary antigen and
      BCG; hemogram assessment according to Garkavi and its dynamic changes 1 month
      after chemoprophylaxis. Basing on these prognostic criteria relevant algorithms
      have been derived.

PMID- 7567861
TI  - [Use of low-intensity lasers in tuberculosis].

PMID- 7567864
TI  - [Malignant neoplasms of lungs based on the data of a tuberculosis hospital].
AB  - The analysis of 61 erroneous admissions to a tuberculous hospital of cancer cases
      proves that tuberculous hospitals have to make annually a lot of differential
      diagnoses to distinguish cancer from tuberculosis. Lung cancer is registered more
      frequently in males aged from 50 to 70, smokers, with a history of
      bronchopulmonary inflammation. 36.07% of lung cancer patients had also various
      forms of intrathoracic tuberculosis. To confirm the diagnosis, invasive
      diagnostic techniques, primarily tracheobronchoscopy, should be employed as early
      as possible. When done outpatient, tracheobronchoscopy promotes earlier reference
      of patients to oncologist decreasing the number of improper hospitalizations to
      tuberculous hospitals.

PMID- 7567863
TI  - [Clinical-morphological characteristics and prevention of steroid tuberculosis].
AB  - The analysis is given of the autopsy material obtained from 39 cases of
      progressive tuberculosis which developed against glucocorticosteroid treatment of
      different diseases. In 28 of 39 patients progression of tuberculosis was stated
      as the main cause of death. There were 12.8% and 43.6% of cases with primary and
      disseminated tuberculosis, respectively. Clinicoanatomical correlations related
      tuberculosis onset to the hormonal treatment regimens. Comparison of the final
      clinical and pathomorphological diagnoses showed that tuberculosis had been
      overlooked in 51.3% of cases.

PMID- 7567862
TI  - [Tuberculosis services of Russia under present-day socioeconomic conditions].
AB  - By the data obtained from a special questionnaire survey current prospects in
      pathological service in Russia, approaches to updating this service, trends in
      basic epidemiological indices, outcomes of treatment and follow-up are outlined.

PMID- 7567867
TI  - [Effectiveness of different methods in the treatment of the main bronchus after
      pneumonectomy].
AB  - Incompetence of the main bronchus within the first 3 postoperative weeks (early
      incompetence) is proposed as a criterion of efficacy of the main bronchus closure
      in pneumonectomy. The authors have performed 495 pneumo- and
      pleuropneumonectomies according to 5 original techniques. No cases of the main
      bronchus incompetence were registered. Indications to each of the bronchus
      treatment techniques are detailed.

PMID- 7567865
TI  - [Diagnosis of lung cancer in a clinical tuberculosis hospital of the Republic].
AB  - The authors point to an increase in combined occurrence of lung cancer and
      tuberculosis. In one-third of all patients cancer arose secondary to
      tuberculosis. In 80% of cases lung cancer was diagnosed at x-ray or
      bronchoscopically. Mantoux test retains its importance for differential
      diagnosis.

PMID- 7567866
TI  - [Temporary occlusion of the bronchi in patients with bronchial fistula].
AB  - Temporary bronchial occlusion to reestablish air tightness of the resected lung
      has been performed in 42 patients. Persistent expanding of the lung occurred
      within 2-3 days in a single early bronchial occlusion (on day 1-2). In late
      occlusion (on day 10-15) the residual pleural cavity disappears on day 30-35.
      Steady expanding of the lung in spontaneous pneumothorax of tuberculous or
      nontuberculous origin and in empyema (89 patients) was observed within 30 days in
      76.5, 87.5 and 36.3% of cases, respectively, unless fistula size is more than 1
      cm. In the rest cases (31.5%) temporary bronchial occlusion allows cutting air
      passage, partial expanding of the lung, cleansing of empyema cavity, alleviation
      of purulent intoxication, this creating conditions for radical surgery.

PMID- 7567868
TI  - [Prosthesis in sequelae of tuberculosis of the femur head].
AB  - Endoprosthetic surgery on the head of the femur to correct aftereffects of
      tuberculous coxitis has been conducted in 23 patients. A combined preoperative
      preparation implying normalization of external respiration and cardiovascular
      function, x-ray examination of the proximal femur and cotyloid cavity specified
      indications for endoprosthetics, method of the pedicle fixation and the scope of
      the intervention. 6-month to 8-year outcomes are available. Overall functional
      results are satisfactory: all the patients but 2 (aged 64-66, underwent unipolar
      endoprosthetics) could walk without support.

PMID- 7567870
TI  - [Possibilities of the use of gas-liquid chromatography in the identification of
      Nocardia microorganisms].
AB  - By determination of fatty acid composition of bacterial cells, gas-liquid
      chromatography can quickly identify Nocardia microorganisms isolated from the
      infected material. The study of fatty acid spectrum of the reference and fresh
      cultures Nocardia has found their homogeneity. Such fatty acids as hexadecenoic,
      hexadecanoic, octadecenoic, octadecanoic and tuberculostearic acids occurred most
      frequently. Differential criteria are proposed for Nocardia microorganisms basing
      on gas-liquid chromatography data on fatty acid spectra from mycobacteria to
      other nonmycobacterial acid-fast microorganisms.

PMID- 7567871
TI  - [Circulating and pulmonary pool of leukocytes in respiratory disorders].
AB  - Total count of activated leukocytes in venous and arterial blood, intensity of
      leukocyte infiltration of the lung were measured in experimental animals (dogs)
      and patients with acute pulmonary diseases. Relationships between circulating and
      marginal leukocyte pools in pulmonary diseases are complicated and heterogeneous.
      There is a certain phase cycle when the lungs either capture the activated cells
      or the activation takes place in pulmonary vessels followed by the cell release
      into the systemic blood stream. This process is dynamic and long-term.

PMID- 7567872
TI  - [Cellular and intracellular markers of lymphocyte activation in patients with
      infiltrative pulmonary tuberculosis].
AB  - The authors investigated markers of activation of CD25-, CD71- and HLD-DR
      molecules on CD3+, CD4+ and CD8+ lymphocytes simultaneously with cytochemical
      activity of the main energetic and synthetic enzymes in 34 patients with new
      onset infiltrative tuberculosis of the lungs and in 30 healthy controls. It was
      found that reduced number of effector and regulatory lymphocyte subpopulations
      was recorded only in patients with advanced infiltrative tuberculosis in line
      with a sharp decline in enzymatic and functional activity of immunocompetent
      cells. In local infiltrative tuberculosis impairment of activation processes
      occurs only at intracellular level in time of energy metabolism shift to
      predominant glycolysis, this allowing lymphocytes to persist functionally active.
      A close relationship is shown between glycolytic enzymes and activation of CD3+
      cells and their subpopulations. Basing on the above findings, one may refer the
      above enzymes to intracellular activation markers of lymphocytes.

PMID- 7567869
TI  - [Biological properties of Mycobacterium tuberculosis in relation to sensitivity
      to antibacterial preparations].
AB  - Biological properties of M. tuberculosis were investigated in 265 patients with
      tuberculosis of respiratory organs. Slow but more massive growth in culture
      medium is characteristic for drug-resistant M.tuberculosis. 32 patients
      discharging drug-resistant M.tuberculosis had unstable drug resistance to
      isoniazid, kanamycin, ethambutol and streptomycin. It is suggested that drug
      resistant M.tuberculosis by virulence are similar to sensitive varieties.

PMID- 7567874
TI  - [Experience in the use of remote infrared thermography in the determination of
      pulmonary tuberculosis activity].

PMID- 7567875
TI  - [Incidence of tuberculosis and its prevention in medical personnel of
      antituberculosis institutions].
AB  - Incidence rate of tuberculosis was ascertained in medical and paramedical staff
      of antituberculosis institutions (ATI) for adults. For the period 1987-1993
      tuberculosis developed in 38 subjects, i.e. 4 times more frequently than in the
      rest adult population of Russia. The physicians catch the infection 1.2 times
      less frequently than paramedical personnel. The highest morbidity was observed in
      the staff of clinical, bacteriological and pathological laboratories. The course
      of tuberculosis in ATI staff is favourable due to early detection and long-term
      treatment but is characterized by frequent attendant diseases, resistance and
      intolerance to antibacterial drugs. Preventive treatment of ATI staff in a
      special sanatorium enhances their resistance to M. tuberculosis infection and
      reduces this infection prevalence in tuberculosis contacts.

PMID- 7567873
TI  - [Experience in the work of a center for diagnosis, treatment and follow-up of
      patients with sarcoidosis].

PMID- 7567876
TI  - [Sarcoidosis: diagnosis, clinical aspects, course and therapy].

PMID- 7567877
TI  - [Lung cancer in patients with tuberculosis discharging Mycobacterium
      tuberculosis].

PMID- 7567878
TI  - [Epidemiological significance of Mycobacterium tuberculosis with primary drug
      resistance].
AB  - Epidemiological situation (1989-1993) in relation to tuberculosis has been
      analyzed for the Khabarovsk region. The data support epidemiological significance
      of M. tuberculosis drug resistance which implies the leading role of exogenic
      mechanism in tuberculosis development. Tuberculosis occurrence in city population
      tends to increase. The number of subjects discharging drug-resistant M.
      tuberculosis has increased by 28%. Contact with tuberculosis patients may be
      responsible for new cases discharging drug-resistant M. tuberculosis in 56.3%.

PMID- 7567879
TI  - [Experience in the work of antituberculosis services of the Mari-El Republic
      under the circumstances of transition to insurance medicine].
AB  - The expenditures of medical insurance companies on the treatment of tuberculosis
      patients reached in 1994 60%. This had a positive effect on the overall results:
      despite increasing tuberculosis prevalence the effectiveness of its treatment is
      very high, while mortality rate is declining.

PMID- 7567880
TI  - [Clinical course of mycobacteriosis in young persons].
AB  - Clinical manifestations of mycobacteriosis in 22 patients aged 16-35 are
      described. In males and females the disease was caused by M. avium and M.
      fortuitum, predisposed by exposure to occupational hazards and previous
      bronchopulmonary and general somatic diseases, respectively. In x-ray pictures of
      the lungs there appeared unilateral lesion in the upper lobe of the right lung.

PMID- 7567881
TI  - [Infectiousness by Mycobacterium tuberculosis of children from tuberculous
      infection foci with different degree of epidemiological risk].
AB  - The examination of 2871 children from tuberculosis foci demonstrates that
      epidemiological risk for children exists not only in conditions of contact with
      active pulmonary tuberculosis carriers, but also in contact with subjects having
      marked residual posttuberculous alterations. This supports the validity of
      referring children in contact with patients from register group VII to
      tuberculosis risk groups.

PMID- 7567882
TI  - [Dynamics of tuberculosis prevalence in children].
AB  - Age- and nationality-specific analysis of the trends observed in tuberculosis
      epidemiology in the Extreme North of Russia objectively shows the role of growing
      reserve of tuberculous infection among native population in small towns for
      epidemiological situation in large cities with formation of common
      epidemiological space in these regions.

PMID- 7567883
TI  - [Current problems of childhood tuberculosis].
AB  - Unsatisfactory antituberculous activity of specialized service has of late
      provoked a noticeable growth in pediatric cases of tuberculosis. The improvement
      of early diagnosis and combined treatment is among measures to correct the
      situation.

PMID- 7567884
TI  - [Methods of detection and characteristics of clinical manifestations of
      tuberculosis in children and adolescents].
AB  - Methods of detection of tuberculous infection in 127 children and adolescents
      treated in special hospitals and sanatoria have seen analyzed. The diagnosis was
      made using tuberculin in 62.2%, epidemiological evidence in 12.6%, fluorographic
      findings in 7.8%, survey of risk groups in 7.1%. 10.2% of the patients sought
      medical advice. A favourable course of the disease was seen in cases detected at
      tuberculin diagnosis and risk group examination. Complications occurred primarily
      in those who sought medical advice.

PMID- 7567885
TI  - [Clinical and immunogenetic aspects of children with local and multiple forms of
      primary tuberculosis].
AB  - Immunogenetic examination of 146 preschool children with local and multiple
      tuberculous lesions and 148 controls found out the key role of unfavourable
      premorbid background (low-quality BCG vaccine, family contacts, associated
      diseases) in the disease onset. General trends in systemic immunity shifts are
      characterized. These depend on the age, inflammation phase, severity of clinical
      symptoms. Representation of antigens HLA DR2, DR5, Cw2, Cw4 indicates that a
      child has a 5-9 times greater risk to develop tuberculosis. These data should be
      allowed for in forming groups of higher risk among children.

PMID- 7567886
TI  - [Clinical and radiographic characteristics of tuberculosis in infants].
AB  - Epidemiological and BCG vaccination background and clinicoroentgenological signs
      of tuberculosis were analysed with reference to epidemiological and BCG
      vaccination background in 177 infants. In infants tuberculosis was represented
      primarily by intrathoracic lymph node tuberculosis running as infiltrative,
      tumorous and minor. Disseminated tuberculosis and meningitis occurred as a rule
      within the first year of life. The disease most frequently arose due to
      tuberculosis contact. More than half of the children from the infection foci
      developed complications. In conditions of massive exogenic superinfection BCG
      vaccination fails to prevent infection and further progression of the disease.

PMID- 7567887
TI  - [Childhood tuberculosis: reflection of today's problems].
AB  - The problem of pediatric tuberculosis is viewed in terms of its connection with
      social and medical setting, epidemiological situation in adult tuberculosis. To
      correct negative trends in tuberculosis prevalence in children efforts should be
      made to eliminate the infection foci, to promote conditioning of population, to
      introduce new programs of health care for mothers and children.

PMID- 7567888
TI  - [Use of different regimes of etiopathogenetic therapy in pulmonary tuberculosis
      in adolescents].
AB  - Clinical parameters were assessed in 178 adolescents aged 15-17 with pulmonary
      tuberculosis. Half of them exhibited changes in the blood picture, immunological
      E-RFC suppression, enhanced lipid peroxidation. The above disturbances and x-ray
      evidence served the basis for differential approach to administration of
      etiotropic treatment. 35 patients received prednisolone in combined therapy. 42,
      25 and 51 patients were given olifen, sodium thiosulfate and tuberculin,
      respectively. 25 patients underwent plasmapheresis. Oriented use of
      etiopathogenetic therapy raised the efficacy of treatment. Clinical effects went
      in parallel with cellular response normalization and lipid peroxidation.

PMID- 7567889
TI  - [Echocardiographic evaluation of pulmonary tuberculosis in adolescent and young
      patients].
AB  - Echo ranging and perfusion scintigraphy were performed in 52 adolescents and
      young subjects with new-onset pulmonary tuberculosis. At admission, enhanced
      myocardial echo resonance was observed in 19.2% of patients. This percentage
      increased to 33.9% at the end of the main treatment course. Systolic pressure in
      the pulmonary artery above 25 mm Hg was recorded in 44.2% of patients. The
      majority of them had disseminated tuberculosis and lymphatic intrathoracic
      disease. Pericardial inflammation developed in 23.1%, pericarditis in 9.6% of the
      examinees.

PMID- 7567890
TI  - [Characteristics of pneumonia in patients with pulmonary tuberculosis].
AB  - In healed tuberculosis, pneumonia more frequently arises in the zones of
      pronounced residual changes. In active tuberculosis combination of tuberculosis
      with pneumonia often takes place in intact bronchopulmonary segments. Pneumonia
      in tuberculous patients takes a lingering course in the presence of
      pneumosclerotic changes in the lungs, tends to acquire bronchial forms, is
      characterized by slow involution of inflammation, runs atypically in combination
      of pneumosclerotic changes in the lungs, bronchial stenoses and abnormal cell
      composition of bronchoalveolar washout. The diagnosis and treatment present
      difficulties in pneumonia location in the zone of distinct post-tuberculous
      pneumosclerosis with small segmental lesion. Resolution of inflammatory foci in
      the lungs in lingering pneumonia may course as long as 8-10 weeks.

PMID- 7567891
TI  - [Detection of Mycobacterium tuberculosis infection in children with
      bronchopulmonary diseases and evaluation of its role in the course of disease].
AB  - Of 190 children under 14 with nonspecific pulmonary diseases (NSPD) 32.4% had
      lingering pneumonia, 20.9% recurrent bronchitis. 54% of lung disease hospital
      inpatients had M. tuberculosis. Normergic and hyperergic tuberculin sensitivity
      was revealed in 85.6 and 14.4% of cases, respectively. 20.5% of the examinees had
      inverted reactions. Clinical symptoms were slight in 13% of children. The rest
      had evident disease. The addition of antituberculous drugs to nonspecific therapy
      in 10.2% of the children has improved treatment outcomes.

PMID- 7567892
TI  - [Characteristics of nephrotuberculosis in children, adolescents and young
      persons].
AB  - According to the author, urogenital tuberculosis in children and young subjects
      occurs in 10% of all the cases with this disease. Antituberculosis service
      registers 71.2% of cases in preschool children, whereas in schoolchildren 70.4%
      of diagnoses are made by general practitioners. 90% of nephrotuberculosis cases
      are detected early, in 85% bacteriological examination.

PMID- 7567894
TI  - [Immunological reactivity in tuberculosis in children].
AB  - Immunological reactivity was assessed comparatively in respiratory, intrathoracic
      and osteoarticular, urinary tuberculosis (122, 133, 38 children, respectively,
      versus 44 controls). References for age were made. The changes in immune system
      varied in nature, severity and relationships. Basing on these findings the author
      has created a complex of most informative tests in the diagnosis of childhood
      tuberculosis adjusted for age and site of the infection focus.

PMID- 7567893
TI  - [Clinical aspects of genital tuberculosis in young women].
AB  - The review of 108 case histories of active genital tuberculosis (GT) in young
      women provided the following information: the symptoms emerged acutely in 30%, GT
      ran under the mask of nonspecific salpingo-oophoritis in 44%, GT was associated
      with pain, general toxicity, blood picture changes in 50, 30 and 66% of patients,
      respectively. In 70.7% of young women tuberculosis affected uterine tubes only,
      whereas in women over 30 years old the infection more frequently occurred in the
      uterus. 63% of GT females were treated surgically.

PMID- 7567895
TI  - [Intoxication indicators in the diagnosis of tuberculosis activity in children].
AB  - It is suggested to judge on the activity of intrathoracic lymph node tuberculosis
      by intoxication assessed from the levels of low- and middle-mass substances in
      blood plasma and red cells. 44 children were examined: 12 children infected with
      M.tuberculosis, 15 children with active tuberculosis of intrathoracic lymph node
      tuberculosis, 17 children treated for this disease by routine methods. Higher
      levels of the above substances were found in children with specific active
      process. Etiopathogenetic treatment for at least 4 months led to reduction of
      intoxication which, however, did not reach control concentrations.

PMID- 7567896
TI  - [Thoracic adenopathy in young patients].

PMID- 7567897
TI  - [Primary generalized tuberculosis in children with lesions of the osteoarticular
      system].

PMID- 7567899
TI  - [Publications of investigators of the St. Petersburg Research Institute of
      Phthisis Pulmonology concerning results of scientific studies on tuberculosis in
      children and adolescents].

PMID- 7567900
TI  - [Tuberculous osteitis in infants].
AB  - Clinical and diagnostic aspects, surgical outcomes, bacteriological findings were
      investigated for 72 infants under 3 years old operated for tuberculous ostitis.
      Tuberculin and seroimmunodiagnosis revealed infection allergy in 1/3 of the
      cases. The treatment comprises radical surgical reconstruction, drug and
      functional therapy. Tuberculous ostitis may arise due to vaccinal strain of M.
      tuberculosis.

PMID- 7567898
TI  - [Early diagnosis and treatment of ocular tuberculosis in children and
      adolescents].
AB  - Pilot experience in the examination and treatment of children with tuberculosis
      admitted to OT department at St. Petersburg Research Institute of
      Phthisiopulmonology is evaluated and current features of tuberculous uveitis are
      characterized. The authors provide recommendations on the research in OT field
      and check-up of OT patients, on design of new schemes of treatment adjusted for
      the disease activity, stage and severity.

PMID- 7567901
TI  - Phylogenetic relationships within Taenia taeniaeformis variants and other taeniid
      cestodes inferred from the nucleotide sequence of the cytochrome c oxidase
      subunit I gene.
AB  - Nucleotide sequence variations in a region of the mitochondrial cytochrome c
      oxidase subunit I (COI) gene (391 bp) were examined within seven species of the
      genus Taenia and two species of the genus Echinococcus, including ten isolates of
      T. taeniaeformis and six isolates of E. multilocularis. More than a 12% rate of
      nucleotide differences between taeniid species was found, allowing the species to
      be distinguished. In E. multilocularis, no sequence variation was observed among
      isolates, regardless of the host (gray red-backed vole, tundra vole, pig, Norway
      rat) or area (Japan, Alaska) from which each metacestode had been isolated. In
      contrast, six distinct sequences were detected among the ten T. taeniaeformis
      isolates examined. The level of nucleotide variation in the COI gene within T.
      taeniaeformis isolates except for one isolate from the gray red-backed vole
      (TtACR), which has been proposed as a distinct strain or a different species, was
      about 0.3%-4.1%, whereas the COI gene sequence for TtACR differed from those of
      the other isolates, with levels being 9.0%-9.5%. Phylogenetic trees were then
      inferred from these sequence data using two different algorithms.

PMID- 7567902
TI  - Carbohydrate involvement in the association of a prokaryotic cell with
      Trichomonas vaginalis and Tritrichomonas foetus.
AB  - Previous studies have shown that Trichomonas vaginalis are capable of ingesting
      bacteria. This observation was confirmed in the present study and extended to
      Tritrichomonas foetus. Using a special strain of Escherichia coli grown under
      conditions that produced fimbriae presenting a lectin-like molecule recognizing
      mannose, we showed that the bacteria attached to and were ingested by
      trichomonads through a mechanism involving cell-to-cell recognition. Absence of
      the fimbriae or addition of alpha-methyl-D-mannoside to the interaction medium
      blocked attachment of the bacteria to the protozoa cell surface. Ingested
      bacteria were later digested within the cytoplasmic vacuole.

PMID- 7567903
TI  - Ultrastructure of Blastocystis hominis cysts.
AB  - Blastocystis hominis cysts were concentrated from human faeces by repeated
      washing in distilled water and centrifugation on Ficoll-Paque. This procedure
      gave a concentrated suspension of cysts without yielding any non-cystic forms.
      The cysts were examined by both transmission (TEM) and scanning electron
      microscopy (SEM). Cysts were surrounded by a fibrillar layer that appeared porous
      in SEM. Many naked cysts without the fibrillar layer were also visible in SEM.
      They were variable in shape but mostly circular to oval. The diameter of the cyst
      without the fibrillar layer was 3.5 microns in both TEM and SEM. The nuclear
      structure was typical of Blastocystis and exhibited multiple mitochondria with
      poorly developed cristae. Glycogen was present in small to large clumps in the
      cytoplasm. The cyst wall was 5-100 nm thick and was bounded internally by an
      electron-dense plasmalemma.

PMID- 7567904
TI  - Serum from Theileria sergenti-infected cattle accelerates the clearance of bovine
      erythrocytes in SCID mice.
AB  - Anemia is a major clinical sign of Japanese bovine theileriosis caused by
      Theileria sergenti. To investigate the possible factors causing anemia in cattle,
      we developed a clearance test for bovine erythrocytes (Bo-RBC) in severe combined
      immunodeficient (SCID) mice. Clearance of Bo-RBC in the SCID mice was
      significantly accelerated when the mice were inoculated with a serum sample
      obtained from an infected calf during a highly parasitized phase but not when
      they were injected with a serum sample obtained during the convalescence phase.
      Acceleration of the clearance of Bo-RBC was also observed in mice treated with
      merozoite extract. Furthermore, the clearance of Bo-RBC that had been treated
      with merozoite extract was accelerated. A significant hemolytic activity in
      infected serum (highly parasitized phase) was observed. Activities sufficient to
      accelerate the clearance of Bo-RBC in SCID mice and to induce in vitro hemolysis
      of Bo-RBC were also observed with a merozoite extract from T. sergenti. The
      results suggest a possible linkage between the in vitro hemolysis of Bo-RBC and
      the acceleration of Bo-RBC clearance in SCID mice.

PMID- 7567905
TI  - Intestinal amebiasis: cyclic suppression of the immune response.
AB  - The cellular immune response was evaluated in a C3H/HeJ mouse model of intestinal
      amebiasis at 5-60 days postinoculation with Entamoeba histolytica. At various
      intervals, spleen lymphocytes were obtained from infected and noninfected control
      mice and cultured with concanavalin A (Con A), pokeweed mitogen (PWM), or ameba
      antigen. E. histolytica infection induced a cyclic depression of DNA synthesis
      when spleen lymphocytes were stimulated with a T-cell mitogen (Con A), a T- and B
      cell (PWM) mitogen, or an ameba antigen. A similar response was observed in the
      determinations of interleukin-2 in the supernatants of Con A-stimulated spleen
      cells from infected mice. When spleen cells from E. histolytica-infected mice
      were stimulated with phorbol myristate acetate plus ionomycin, results indicated
      a signal-transduction defect. These alterations, observed at the cellular level,
      might facilitate invasion of the host by the parasite.

PMID- 7567908
TI  - Cadmium concentrations in two adult acanthocephalans, Pomphorhynchus laevis and
      Acanthocephalus lucii, as compared with their fish hosts and cadmium and lead
      levels in larvae of A. lucii as compared with their crustacean host.
AB  - Adults of Pomphorhynchus laevis and Acanthocephalus lucii were analyzed for
      cadmium by atomic absorption spectrometry. Their cadmium concentrations were
      compared with those found in different tissues (muscle, liver, and intestine) of
      their final hosts the chub and perch. Additionally, the cadmium and lead
      concentrations in larvae of A. lucii and their intermediate host Asellus
      aquaticus were determined. Regarding the adult acanthocephalans, the parasites
      showed several times more cadmium than did the tissues of their fish hosts. In
      contrast to this obvious accumulation capacity of adult A. lucii, the larvae
      contained less cadmium than did their crustacean host. Thus, the cadmium
      concentration in the larval stages was nearly 180 times lower than that measured
      in the adult worms. According to the present results, it appears that the heavy
      metals cadmium and lead are predominantly accumulated by the adult
      acanthocephalans inside the fish gut and not by the larvae inside the hemocoel of
      the crustaceans.

PMID- 7567910
TI  - Life-cycle description and comparison of Diplostomum spathaceum (Rudolphi, 1819)
      and D. pseudobaeri (Razmaskin & Andrejak, 1978) from rainbow trout (Oncorhynchus
      mykiss Walbaum) maintained in identical hosts.
AB  - Precise identification of members of the genus Diplostomum is difficult in that
      many larval stages have been described and named separately from their adult
      forms. In this study, the life cycles of two Diplostomum spp. were established
      using metacercariae obtained from the eyes of rainbow trout. The parasites were
      identified as D. spathaceum and D. pseudobaeri using a procedure and key devised
      by Shigin. Each life cycle was completed in the laboratory using domestic
      chickens (Gallus gallus domesticus L.) as definitive hosts and Lymnaea peregra
      (Muller) and rainbow trout as first and second intermediate hosts, respectively.
      Utilizing identical hosts minimised host-induced morphological variations and
      allowed comparisons of anatomical features to be made. Light and scanning
      electron microscopy were used to study each developmental stage and detailed
      descriptions of the life cycles were compiled. The results obtained may go some
      way to resolving the confusion that surrounds Diplostomum taxonomy.

PMID- 7567907
TI  - Differentiating between Besnoitia besnoiti from cattle and Sarcocystis hoarensis
      from rodents.
AB  - To provide a biological basis for studies designed to establish the mode of
      transmission of the veterinary pathogen Besnoitia besnoiti, we compared salient
      features of this pathogen in cattle with those of Sarcocystis hoarensis in
      rodents. The cysts and cystozoites of these organisms can readily be
      distinguished morphologically. In contrast to S. hoarensis, which is well adapted
      to rodents, B. besnoiti fails to mature in jirds or mice and generally is lethal
      in jirds. Serological reagents discriminately detect these pathogens. B.
      besnoiti, therefore, can unambiguously be differentiated from S. hoarensis either
      by morphological or serological methods or on the basis of experimental
      comparisons of virulence in laboratory rodents.

PMID- 7567909
TI  - Interferon-gamma levels during the course of Trypanosoma cruzi infection of
      Calomys callosus (Rodentia-Cricetidae) and Swiss mice.
AB  - Serum levels of interferon-gamma (IFN-gamma) were evaluated in Calomys callosus
      and Swiss mice during the course of infection by four strains of Trypanosoma
      cruzi. All strains stimulated the production of this interleukine; however, the
      timing of its onset and permanence varied among strains and between the two
      animal models. When chronically infected animals with no detectable serum IFN
      gamma were challenged with the homologous strain, they produced quantities
      comparable with those obtained during the acute phase of infection. In C.
      callosus there was a correlation between H2O2 liberation by peritoneal
      macrophages and serum IFN-gamma levels, whereas no such correlation was found in
      mice. C. callosus had a higher capacity to heal histopathological lesions,
      whereas lesions in mice were progressive. The results obtained suggest that C.
      callosus develops well-adapted immune mechanisms that may be important for its
      role as a reservoir of T. cruzi.

PMID- 7567906
TI  - The life cycle of Contracaecum osculatum (Rudolphi, 1802) sensu stricto
      (Nematoda, Ascaridoidea, Anisakidae) in view of experimental infections.
AB  - Hatched, ensheathed third-stage larvae of Contracaecum osculatum, 300-320 microns
      long, were shown to be infective to copepods, to nauplius larvae of Balanus and
      to small specimens of fishes (sticklebacks, O-group eelpout). Other fishes such
      as gobies and small flatfishes became infected by ingesting infected crustaceans.
      Cod were infected by being given infected small fishes. In the crustacean
      paratenic hosts, little growth of the larvae occurred, if any. In the liver
      sinusoids of sticklebacks and gobies the length of most of the unencapsulated
      third-stage larvae had not even doubled within 6 months of infection. The fate of
      larvae (max. 2 mm long) given to cod via infected intermediate fish hosts was
      apparently decided by the size of the larvae only. Small larvae became
      encapsulated and eventually died in the liver and wall of the gastrointestinal
      tract. Larger larvae migrated to the liver parenchyma, where some grew to a
      length of as much as 10 mm. The growth of the larvae in sticklebacks was shown
      not to be affected by an increase in temperature (infected fish being transferred
      from 8 degrees to 14 degrees and 20 degrees C), by the intensity of infection
      and, partly, by the age of infection (e.g. some 2-week-old and 6-month-old larvae
      were of identical size). In the liver and mesentery of plaice the third-stage
      larvae developed via copepod paratenic hosts to infectivity (i.e. to more than 4
      mm in length), showing that the life cycle may be completed with an optional
      paratenic invertebrate host and only one intermediate fish host.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7567911
TI  - The effect of dexamethasone on the course of Echinostoma caproni and E. trivolvis
      infections in the golden hamster (Mesocricetus auratus).
AB  - Golden hamsters (Mesocricetus auratus) were given intramuscular injections of
      dexamethasone and infected with Echinostoma caproni or E. trivolvis. All animals
      were necropsied on day 14 postinfection. Dexamethasone treatment at high doses
      resulted in increased parasite recovery. Decreased total white blood cell counts
      and decreased relative splenic weights were observed in corticosteroid-treated
      hamsters. Dexamethasone-treated animals also demonstrated significantly lower
      mean parasite dry weights for E. caproni. Specific serum IgG against the
      parasites was not detected in corticosteroid-treated hamsters on day 14
      postinfection.

PMID- 7567912
TI  - Lipids of fish parasites and their hosts: fatty acid fingerprints of four species
      of acanthocephalans and of their hosts' intestinal tissues.
AB  - The fatty acid fingerprints of total lipid extracts from the four fish parasites
      Acanthocephalus lucii, Neoechinorhynchus rutili, Paratenuisentis ambiguus, and
      Pomphorhynchus laevis were investigated by capillary gas-liquid chromatography
      (GLC). The fatty acid patterns of the parasites were compared with those of their
      respective host tissue, viz., intestinal tract tissue of infected perch, brown
      trout, eel, and chub. The highly complex gas chromatograms revealed significant
      differences not only between parasite and host tissue but also between the
      parasites themselves. For instance, all the parasites contained much more
      eicosapentaenoic acid (20:5n-3) than did the respective fish intestinal tissue.
      Differences were also observed between the presoma and metasoma of Pomphorhynchus
      laevis.

PMID- 7567913
TI  - Morphology and cytology study of Foleyella agamae complex (Nematoda: Filarinae)
      infecting the agamid lizard Agama agama in Nigeria.
AB  - Three cytotypes of Foleyella agamae were isolated from naturally infected wild
      caught Agama agama in Nigeria. Cytotype A (2n = 8) has a body length/oesophageal
      length ratio (L/O) of 87.6 +/- 14.2 in female worms and a large somatic size
      (length, 63.8 +/- 12.7 mm in female worms and 25.5 +/- 3.4 mm in males). Cytotype
      B (2n = 6) has an L/O of 43.4 +/- 6.6 in females and a small to average somatic
      size (length, 36.7 +/- 11.9 mm in females and 19.5 +/- 2.3 mm in males). Cytotype
      C (2n = 4) has an L/O of 23.8 +/- 8.2 in female worms and a small somatic size
      (length, 18.8 +/- 3.8 mm in females and 14.1 +/- 3.0 mm in males). No cytotype
      with odd numbers of chromosomes was observed. Comparisons with similar types of
      speciation in medically important filarial parasites were drawn. Introgressive
      hydridisation in the speciation of filarial parasites is postulated.

PMID- 7567915
TI  - A comparative study of the shedding of cercariae of Schistosoma haematobium in
      newborn Bulinus truncatus.
AB  - A comparative study of the shedding of cercariae of Schistosoma haematobium was
      performed in Bulinus truncatus and Planorbarius metidjensis individually exposed
      to 5 miracidia in their first 72 h of life. No significant difference was noted
      between the mean values of the two snail groups concerning the prepatent period
      duration (53-57 days at 24 degrees-26 degrees C), the patent period duration (41
      days for B. truncatus, 70 days for P. metidjensis), or the total number of
      cercariae (1,499 per B. truncatus, 1,935 per P. metidjensis). Successive periods
      of heavy and low production were encountered in the shedding of cercariae;
      however, the periodicity was identical in the two snail species (25-27 days) and
      the emergence of cercariae peaked between 11 a.m. and 1 p.m.

PMID- 7567914
TI  - Comparative studies on the productivity of Fasciola gigantica and F. hepatica
      sporocysts in Lymnaea tomentosa that died after a cercarial shedding or without
      emission.
AB  - A histology study was performed on Fasciola gigantica- or F. hepatica-infected
      Lymnaea tomentosa that died after a cercarial shedding or without emission to
      compare the parasite productivity of each trematode. Degenerated rediae increased
      in number throughout the experiment. Their number rose rapidly after day 79 in
      snails that died after shedding in the F. gigantica group; they increased more
      slowly in snails that died without shedding. In the F. hepatica group the number
      rose after day 63 in the former snails and after day 79 in the latter. The
      contents of normal rediae evolved inversely. The number of morulae, for example,
      dropped rapidly after day 79 in the F. gigantica group. In the F. hepatica group
      it dropped after day 63 in snails that died after shedding and decreased after
      day 79 in the other dead snails. Free and degenerated cercariae were more
      numerous in snails that died without emission than in those that died at
      shedding. They rapidly increased in number after day 77. The numbers of rediae of
      F. gigantica were substantially greater than those of F. hepatica. In each group
      considered separately, it was likewise higher in snails that died without
      shedding than in those that died after the shedding of cercariae.

PMID- 7567916
TI  - Antibody response to a protease secreted by Trichinella spiralis muscle larvae.
AB  - In the present study we analyzed the humoral response of Trichinella spiralis
      infected mice to a 35-kDa protease (purified from the excretory-secretory
      products of T. spiralis muscle larvae) by a Western-blot procedure and an enzyme
      linked immunosorbent assay (ELISA) technique using a panel of postinfection mouse
      anti-Trichinella sera. The results demonstrated that this response was time
      dependent and that infected mice could be distinguished from controls. In
      addition, inhibition assays demonstrated that these antisera were capable of
      abolishing the proteinase activity of the 35-kDa protease in vitro. The
      occurrence of proteases seems to be a very common feature in parasite crude
      extracts and excretory-secretory products (McKerrow 1989). It is also known that
      these enzymes are implicated in important host-parasite interactions, and for
      this reason, recent reports have proposed the use of parasite proteases both as
      alternative targets for an induced immune response and as a rich source of
      antigenic material for diagnostic testing (Hotez et al. 1985; Yamasaki et al.
      1989; Song et al. 1990; Frank and Grieve 1991; Britton et al. 1992; Song and
      Chappell 1993). We have recently purified a protease (mol. wt., 35 kDa) from the
      excretory-secretory (ES) products of Trichinella spiralis (GM-1 strain) muscle
      larvae and established some of the biochemical properties of this protease (Armas
      Serra et al. 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567917
TI  - DNA recognition code of transcription factors.

PMID- 7567919
TI  - Contact pattern-induced pair potentials for protein fold recognition.
AB  - The protein structure prediction problem is considered as a problem of fitting a
      sequence into a folding motif. We focus on finding an approximative structure
      representation providing the best preferences or contact energies. A 2-D
      structure description in the form of specific contact matrices is used. The main
      features of our approach are (i) only contacts involved in characteristic
      interaction patterns are considered, (ii) amino acid pair preferences or contact
      energies related to these interaction patterns are derived from the structural
      database and (iii) from the evaluation of individual structure elements,
      hypotheses on the alignment of a new sequence to a given structure may be
      derived. Results are demonstrated in particular to examples of the blue copper
      proteins.

PMID- 7567918
TI  - DNA recognition and superstructure formation by helix-turn-helix proteins.
AB  - The way helix-turn-helix proteins recognize DNA is analysed by comparing their
      sequences, structures, and binding specificities. Individual recognition helices
      in these proteins bind to four DNA base pairs with the same geometry. However,
      pairs of recognition helices in the protein dimers can have different separations
      and orientations. These differences are used for discriminating between DNAs
      which have different superstructures, in particular, different numbers of base
      pairs between sets of the four base pairs.

PMID- 7567920
TI  - Comparison of spatial arrangements of secondary structural elements in proteins.
AB  - We have developed a new method of protein structure comparison based on spatial
      arrangements of secondary structural elements (SSEs). Each SSE is represented by
      a single vector, and common spatial arrangements of vectors in a pair of proteins
      are detected. The method allows not only insertions and deletions of SSEs, but
      also topological permutations. It has a flexible target function that can be
      adjusted depending upon particular levels or definitions of structural
      similarity, and it is fast enough to allow structural comparisons for many pairs
      of proteins. The parameters for the target function are determined based on
      distributions of the geometrical variables for the spatial arrangements of the
      equivalent SSEs in well-known structural motifs. The obtained parameter set is
      tuned for detecting relatively strong structural similarity. We report several
      tests on examples including comparisons of known structural similarity and
      database searches for a target structure, and examine the results when this
      parameter set is used for the comparison of distantly related structures.

PMID- 7567921
TI  - Side-chain prediction by neural networks and simulated annealing optimization.
AB  - The prediction of the side-chain positions of proteins of known tertiary backbone
      structure was accomplished by a combination of neural networks and a simulated
      annealing method. Neural networks were used to generate distributions of side
      chain dihedral angles. By eliminating network outputs with low activities, we
      were able to generate a reduced conformational space in which Monte Carlo
      simulated annealing was carried out to optimize side-chain positions. In this
      study of 12 proteins, the average fractions of correct chi 1, chi 2 and combined
      chi 1 and chi 2 (to within 40 degrees of actual structure) were 82, 72 and 68%
      respectively.

PMID- 7567922
TI  - Protein docking for low-resolution structures.
AB  - A typical problem for a docking procedure is how to match two molecules with
      known 3-D structure so as to predict the configuration of their complex. A very
      serious obstacle to docking is an inherent inaccuracy in the 3-D structures of
      the molecules. In general, existing molecular recognition techniques are not
      designed for cases where (i) conformational changes upon macromolecular complex
      formation are substantial or (ii) the X-ray data on one or both (macro) molecules
      are not available, and the structures, based on alternative sources (NMR,
      modeling), are not well defined. We designed a direct computer experiment using
      molecules totally deprived of any structural features smaller than 7 A. This was
      performed on the basis of a previously developed docking algorithm. The modified
      procedure was applied to a number of known protein complexes taken from the
      Brookhaven Protein Data Bank. In most cases, a pronounced trend towards the
      correct structure of the molecular complex was clearly indicated and the real
      binding sites were predicted. The distinction between the prediction of the
      antigen-antibody complex and other molecular pairs may reflect important
      differences in the principles of complex formation. The results strongly suggest
      the use of our recognition procedure for docking studies where the detailed
      structures of the molecules are lacking.

PMID- 7567927
TI  - Sometimes we don't look like our parents.

PMID- 7567924
TI  - Prediction of hypervariable CDR-H3 loop structures in antibodies.
AB  - The structure of the most variable antibody hypervariable loop, CDR-H3, has been
      predicted from amino acid sequence alone. In contrast to other approaches
      predictions are made for loop lengths up to 17 residues. The predictions have
      been achieved using artificial neural networks which are trained on a large set
      of loops from the Brookhaven Protein Databank which have structures similar to
      CDR-H3. The loop structures are described by the two backbone dihedral angles phi
      and psi for each residue. For 21 CDR-H3 loops unique to the neural network, the
      prediction of dihedral angles leads to an average root mean square deviation in
      the Cartesian coordinates of 2.65 A. The present method, when combined with
      existing modelling protocols, provides an important addition to the structural
      prediction of the complementarity determining regions of antibodies.

PMID- 7567923
TI  - Comparative molecular dynamics simulation studies of salmon and bovine trypsins
      in aqueous solution.
AB  - The flexibility and conformational behaviour of salmon and bovine trypsins were
      modelled with a 300 ps molecular dynamics simulation in aqueous solution.
      Trajectories from both trypsins were analysed to eventually detect differences in
      mobility that could explain observed variations in stability and activity. The
      simulations were performed at 300 K with all the acidic groups deprotonated and
      the basic groups protonated. The radius of gyration, the overall r.m.s. deviation
      from the starting structure as a function of time, together with the r.m.s.
      deviation from the starting structures as a function of residue number,
      demonstrated that the simulations were stable and representative of the X-ray
      structures of both enzymes. Isotropic Debye-Waller factors were calculated from
      the fluctuations for main-chain atoms and were in good agreement with
      experimental values. The overall dynamic properties of the two enzymes were
      similar. Based on the present 300 ps molecular dynamics simulation, it cannot be
      concluded that either of the two enzymes is more 'flexible' than the other.
      However, there are clearly differences in mobility on a more detailed level and
      for particular regions.

PMID- 7567926
TI  - Identifying a putative common binding site shared by substance P receptor and an
      anti-substance P monoclonal antibody.
AB  - Substance P G-protein coupled receptor and the antigen recognition site of a
      monoclonal antibody raised against substance P share a stretch of five contiguous
      identical amino acids. This observation prompted us to build an atomic model of
      both the receptor and the antibody and to analyse their common features. In
      particular, we report here that a pocket of similar size and composition is
      present in both proteins, strongly suggesting a similarity in the mode of binding
      of both macromolecules to substance P. From the analysis of our models, the
      available data on the mode of binding of the antibody to substance P and recent
      data on substance P receptor mutants, we concluded that the pocket is very likely
      to be involved in binding of the C-terminal 'message sequence' of the tachykinin.
      This allowed us to suggest specific site-directed mutants of the receptor which
      should shed some light on the mechanism of peptide recognition by G-protein
      coupled receptors.

PMID- 7567928
TI  - Becoming a Third World country: the verbal autopsy.

PMID- 7567925
TI  - Secondary structure prediction of the H5 pore of potassium channels.
AB  - The 'H5' segment located between the putative fifth and sixth transmembrane
      helices is the most highly conserved region in voltage-gated potassium channels
      and it is believed to constitute a major part of the ion conduction path (pore).
      Here we present a two-step procedure, comprising secondary structure prediction
      and hydrophobic moment profiling, to predict the structure of this important
      region. Combined results from the application of the procedure to the H5 region
      of four voltage-gated and five other K+ channel sequences lead to the prediction
      of a beta-strand-turn-beta-strand structure for H5. The reasons for the
      application of these soluble protein methods to parts of membrane proteins are:
      (i) that pore-lining residues are accessible to water and (ii) that a large
      enough database of high-resolution membrane protein structures does not yet
      exist. The results are compared with experimental results, in particular
      spectroscopic studies of two peptides based on the H5 sequence of SHAKER
      potassium channel. The procedure developed here may be applicable to water
      accessible regions of other membrane proteins.

PMID- 7567929
TI  - Diabetic mastopathy: a clinicopathologic study in palpable and nonpalpable breast
      lesions.
AB  - Diabetic mastopathy is a distinct clinicopathologic entity with specific
      histopathologic characteristics which include keloidal fibrosis, epithelioid
      fibroblasts, widespread periductal/lobular lymphocytic infiltration, and
      widespread perivascular lymphocytic infiltration. We report the clinical and
      histopathologic breast tissue findings of 20 patients with diabetes mellitus as
      compared to 20 age-matched controls. The control patients also were matched for
      diseases other than diabetes mellitus. All patients with diabetes mellitus showed
      at least one of the histologic findings of diabetic mastopathy: 13 patients (65%)
      showed all four histopathologic characteristics; one patient showed three; one
      patient showed two; and five patients showed one feature. The 20 control patients
      did not demonstrate any of the four histopathologic features of diabetic
      mastopathy. We confirm previously reported findings of diabetic mastopathy
      presenting as palpable breast masses in insulin-dependent diabetics. However, we
      also suggest that diabetic mastopathy should be expanded to include the
      histopathologic findings characteristic in diabetic patients with nonpalpable
      mammographic abnormalities and breast tissue distant to the site of involvement
      by carcinoma.

PMID- 7567932
TI  - Papillary carcinoma of the thyroid gland with fibromatosis-like stroma: a case
      report and review of the literature.
AB  - A new case of a rare variant of papillary carcinoma of the thyroid gland with
      fibromatosis-like stroma is reported. The patient was a 43-yr-old woman who had a
      well demarcated tumor that showed an expansive growth from the left thyroid lobe
      into perithyroidal soft tissues. Histologically, the tumor was composed
      predominantly of a fibromatosis-like stroma in which were diffusely dispersed
      small follicles of papillary carcinoma. At the advancing front of extrathyroidal
      extension of the tumor, fibromyxomatous changes of soft tissues were preceded by
      infiltration of the papillary carcinoma component. Immunohistochemistry and
      electron microscopy showed that the stromal cells had a myofibroblastic nature.
      One metastatically involved lymph node did not show fibromatosis-like stroma. The
      patient has remained well with no evidence of recurrence for 1 yr.

PMID- 7567931
TI  - DNA aneuploidy in morphologically normal colons from patients with colon cancer.
AB  - DNA aneuploidy is common in colon carcinoma, colonic polyps, and ulcerative
      colitis. We found an interesting subset of patients with colon cancer. These
      individuals (14 of 230 cases, 6%) had hypodiploid aneuploidy in their
      morphologically normal-appearing colonic tissue. The aneuploid fractions were
      small, making up between 10 to 15% of the total events, and the ploidy pattern
      was not related to the ploidy pattern of the tumor. The clinical findings of the
      14 patients were compared with those of patients who had diploid normal colons by
      age, location of the tumor, Dukes stage, and percent aneuploidy in the main
      tumor; the two groups were comparable. Both the normal colon and carcinomas of
      the 14 cases were studied by a newly developed "enriched" polymerase chain
      reaction for K-ras mutations. No K-ras mutations were found in the normal
      tissues, but mutations were found in the tumors of four cases. Cells from some
      colon cancers have a high degree of genetic instability, as shown by numerous
      mutations throughout the genome. Analysis of eight matched colon cancers and
      aneuploid, morphologically normal-appearing colons for genetic alterations, as
      measured by shifts in the electrophoretic mobility of microsatellite repeat
      fragments, showed that only one of eight colon cancer samples had microsatellite
      instability, which is the expected frequency. Taken together, the data suggest
      that individuals with colon cancer may have morphologically normal colonic
      tissue, which is genetically abnormal, and this abnormality may precede the
      development of mutations in K-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567933
TI  - Distribution of cytokeratin 19-positive biliary cells in cirrhotic nodules,
      hepatic borderline nodules (atypical adenomatous hyperplasia), and small
      hepatocellular carcinomas.
AB  - Borderline nodule (BN) in the cirrhotic liver is considered to be a precancerous
      lesion leading to hepatocellular carcinoma (HCC). We investigated the
      distribution of cytokeratin 19 (CK 19)-positive biliary cells, recognizable by a
      monoclonal antibody AE1, in normal livers, chronic active hepatitis, cirrhosis,
      BN, and small HCC. The CK 19-positive biliary cells in the hepatic parenchyma
      were clearly divisible into two types (I and II). Type I cells were located
      within the hepatic parenchyma as small clusters forming small tubules
      (intraparenchymal ductules). Type II cells were bile ductules located in the
      peripheral rim of the hepatic lobules or hepatocellular lesions (peripheral
      ductular reaction) and were continuous with proliferated bile ductules in fibrous
      septae or portal tracts. In chronic active hepatitis and regenerative nodules of
      cirrhosis, a few type I cells and a variable number of type II cells were
      present. In the BN, all cases harbored a few type I cells as well as a variable
      number of type II cells. The type II cells in the BN were fewer in number and
      more randomly distributed than those in chronic active hepatitis and cirrhosis.
      Malignant foci in some BNs lacked CK 19-positive biliary cells. In small HCC, no
      CK 19-positive biliary cells were found; instead, AE1-positive HCC cells were
      present in three cases (17%). Although a great majority of type I cells
      corresponded to intraparenchymal ductules, some type I cells in the BN were
      composed of rather large tubules considered as interlobular bile ducts.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7567934
TI  - Pseudoinvasion in intraductal carcinoma.
AB  - Fine-needle aspiration, stereotactic biopsies, and guide wire localization have
      introduced an element of pre-excision trauma to mammary lesions. Dislodgement of
      tumor cells may result in diagnostic difficulties and misinterpretation of a
      tissue artifact as an invasive carcinoma. Eight breast biopsy specimens with
      intraductal carcinoma (ranging from cribriform to comedo types) displayed changes
      suggestive of an invasive carcinoma. Three of the patients had a prior history of
      needle aspiration; the remaining five women had undergone needle localization to
      guide the biopsy. In all cases, two or more dislodged tumor cell clusters were
      found in the stroma or adipose tissue either immediately adjacent to a disrupted
      duct with intraductal carcinoma or in the nearby stroma. Those cases with prior
      needle aspiration were associated with significant hemorrhage and reactive
      changes with small, rounded clusters of tumor cells within pools of blood. The
      needle localization specimens had minimal tissue reaction with larger fragments
      of detached cell clusters. Breast trauma by a puncturing instrument (needle or
      guide wire) can disrupt mammary ducts with intraductal carcinoma and dislodge the
      proliferating cells into the surrounding stroma. The dislodged cells simulate
      invasion. To minimize damage to the architectural integrity of the lesion under
      investigation, limits should be imposed on the number of needle passes.

PMID- 7567930
TI  - Peripheral T-cell lymphoma in a chronically immunosuppressed renal transplant
      patient.
AB  - Non-Hodgkin large cell lymphomas occurs more commonly in organ-transplanted
      patients than in the general population. They are usually of B-cell origin
      whereas T-cell lymphomas are rare. We report a new case of peripheral T-cell
      lymphoma in an immunosuppressed renal transplanted patient. The patient presented
      a hepatosplenic mass with a widespread extension causing serious pancytopenia. It
      was classified as a pleomorphic medium and large cell type and corresponded to
      the "common" alpha beta-TCR type lymphoma. Lymphomatous cells exhibited an
      incomplete mature T-cell phenotype. T-cell receptor gene clonal rearrangement
      associated with a germline configuration of the immunoglobulin heavy chain gene
      confirmed a clonal T-cell genotype. By using both Southern blot analysis and
      polymerase chain reaction, we failed to demonstrate any association with Epstein
      Barr virus or human T-cell lymphotropic virus type I or type II.

PMID- 7567935
TI  - Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and
      Merkel cell carcinomas.
AB  - Keratin 20 is a recently identified keratin protein distributed particularly in
      the epithelial cells of the gastrointestinal tract. In this study, keratin 20 was
      immunohistochemically evaluated in 788 epithelial tumors of different organs.
      Keratin 20 was consistently present in colonic adenocarcinomas and their
      metastases in lymph nodes, liver, lung, and ovaries; most primary and metastatic
      colon carcinomas showed high numbers of positive cells independent of their level
      of differentiation. Adenocarcinomas of the upper gastrointestinal tract,
      pancreas, and cholangiocarcinomas showed variable reactivity. Hepatocellular
      carcinomas and carcinoid tumors often showed focal reactivity limited to
      scattered tumor cells. In contrast, keratin 20 was virtually absent in primary
      adenocarcinomas of lung, ovaries, and endometrium. Notable exceptions among
      ovarian tumors were the mucinous neoplasms that showed variable, sometimes
      significant keratin 20 reactivity. Transitional cell carcinomas irrespective of
      grade were usually positive, whereas most prostatic and renal adenocarcinomas
      were negative or showed only single positive cells. Typically negative were
      squamous cell carcinomas of all organs and carcinomas of the breast. Merkel cell
      carcinomas of the skin showed consistent reactivity, whereas small cell
      carcinomas of the lung were negative. On the basis of these observations, keratin
      20 seems to be a suitable adjunct marker to evaluate the primary origin of
      carcinomas in specific contexts, especially to separate adenocarcinomas of
      gastrointestinal versus nongastrointestinal origin.

PMID- 7567936
TI  - Breakpoint cluster region, immunoglobulin, and T-cell receptor gene rearrangement
      analysis in juvenile chronic myelogenous leukemia.
AB  - Juvenile chronic myelogenous leukemia (JCML) is a heterogeneous disorder composed
      of Philadelphia chromosome-positive (Ph+) CML, which is similar to CML in adults,
      and Ph-negative (Ph-) CML, a childhood myelodysplasia resembling chronic
      myelomonocytic leukemia in adults. These two disorders are not always readily
      separable by leukocyte alkaline phosphatase (LAP) scoring and by karyotyping, yet
      they have different courses and outcomes. We compared the results of breakpoint
      cluster region (bcr) gene rearrangement analysis with LAP score and karyotype in
      these patients. In addition, analysis for immunoglobulin and T-cell receptor gene
      rearrangement was done to investigate the possibility of mixed myeloid and
      lymphoid lineage, which has been shown to occur in childhood acute myelogenous
      leukemia and CML in blast crisis. Peripheral blood and bone marrow samples from
      six patients with JCML aged 5 to 19 yr were analyzed. One case was Ph+, and five
      were Ph- by karyotyping. Two samples showed LAP scores of 5 and 11 (one Ph+ and
      one Ph-); others were normal. All were digested with EcoRI, HindIII, and BamHI
      for immunoglobulin heavy and light chains and T-cell receptor beta-chain analysis
      and, in addition, with BglII for bcr analysis. Samples were hybridized with
      probes to JH, JK, CT beta, and bcr (Oncor). A bcr rearrangement was shown in the
      Ph+ sample; all others, including one with a very low LAP score, were negative.
      No JH, JK, or CT beta rearrangements were detected.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7567937
TI  - Screening for urothelial malignancies by cytologic analysis and flow cytometry in
      a community urologic practice: a prospective study.
AB  - A prospective study was initiated to compare the ability of flow cytometry and
      cytologic analysis to detect malignant cells in urine obtained at the time of
      cystoscopy. The population studied consisted of patients from general urologic
      practices who were undergoing cystoscopy in a single community hospital. Over a 1
      yr period, 335 specimens from 317 patients were studied. Nineteen biopsy-proven
      urothelial malignancies were identified. Cytologic examination of urine obtained
      at the time of cystoscopy was positive in seven of these cases, and an aneuploid
      population of cells was identified by flow cytometry in three cases. All three
      cases of high-grade transitional cell carcinoma and carcinoma in situ were
      correctly identified by the combination of cytologic examination and flow
      cytometry; however, only four of 16 low-grade superficial papillary transitional
      cell carcinomas were recognized cytologically, with only one being aneuploid. The
      combination of cytologic analysis and flow cytometry did not increase the
      diagnostic sensitivity above that achieved with cytologic testing alone (overall
      sensitivity, 37%). We conclude that flow cytometry and cytologic analysis, either
      individually or in combination, are too insensitive for use in a routine
      screening program for urothelial malignancy in a community hospital setting
      because of the inability of either method to detect low-grade transitional cell
      carcinomas reliably.

PMID- 7567938
TI  - Association of hepatic veno-occlusive disease with the acquired immunodeficiency
      syndrome.
AB  - AIMS: Observation of a patient with the acquired immunodeficiency syndrome and
      veno-occlusive disease (VOD) at autopsy prompted us to review the liver pathology
      of autopsied patients with human immunodeficiency virus seropositivity and/or
      acquired immunodeficiency syndrome (HIV/AIDS) to determine the frequency of
      occurrence of VOD and the circumstances in which it arose. METHODS: the patients
      studied had been autopsied at The Johns Hopkins Hospital, a referral center,
      between April 1981 and July 1993. We reviewed 275 adult HIV/AIDS patients
      autopsied with liver slides available for evaluation. Twenty cases fulfilled the
      pathologic criteria for VOD, central vein obliteration and sclerosis, sinusoidal
      congestion and fibrosis, and perivenular hepatocellular degeneration and
      necrosis. The autopsy cases were compared for age, race, gender, duration of HIV
      infection, and risk factor for the acquisition of HIV infection. The clinical and
      pathologic features of the 20 cases with VOD were reviewed. RESULTS: of the 275
      HIV/AIDS patients, 20 (7.3%) had VOD. The average age was 41 yr (range 30-58) and
      most cases were black males (15 black, 5 white, and 18 male). The duration of HIV
      infection ranged from 6 mo to 8 yr (mean, 19 mo). The risk factor for acquiring
      HIV infection was primarily intravenous drug abuse (12 of 20, 60%). Six patients
      had homosexual or bisexual contacts, and two had other or unknown risk factors.
      In contrast, among the total of 275 HIV/AIDS autopsied patients reviewed, only 72
      (26%) reported intravenous drug abuse whereas 157 (57%) individuals listed
      homosexual or bisexual contacts as a risk for developing HIV infection. Forty-six
      patients (17%) had other or unknown means of HIV infection. Statistical analysis
      by risk factor showed that intravenous drug abuse was statistically significant
      as a predictor for the development of VOD in an HIV/AIDS patient (P < 0.005).
      CONCLUSIONS: VOD of the liver can be seen in patients with HIV/AIDS and is
      associated with intravenous drug abuse.

PMID- 7567939
TI  - Cardiac papillary fibroelastoma: an immunohistochemical investigation and unusual
      clinical manifestations.
AB  - Cardiac papillary fibroelastoma (CPF) is a morphologically distinctive, but rare,
      cardiac lesion that is usually found incidentally at autopsy or during open heart
      surgery. Because of improved diagnostic imaging techniques, the premortem or
      preoperative diagnosis of CPF is becoming more frequent. The histogenesis of CPF,
      however, remains controversial. Herein we report an immunohistochemical
      investigation of 11 cases of CPF; two cases showed unusual embolization
      phenomena, including one with histologically documented pulmonary arterial
      embolism. For comparison, nine cardiac myxomas (CMs) and eight examples of
      organizing thrombi were also studied. Immunohistochemical markers included
      keratin, vimentin, collagen type IV, muscle-specific actin, desmin, factor VIII
      related antigen, CD34, and S-100 protein. The cells covering the surface of both
      CPFs and CMs were positive for vimentin, factor VIII-related antigen, and CD34,
      in keeping with their presumed vascular endothelial origin. Interestingly, the
      surface lining cells were also positive for S-100 protein in all CPF and in eight
      of nine CMs. In CPF, collagen type IV showed multilayered linear staining beneath
      the surface that was virtually identical to the staining pattern for elastic
      tissue. The major immunophenotypic difference between CPF and CM is the frequent
      presence of muscle-specific actin in the stellate cells of the stroma in CM but
      not in CPF. Although this study did not clarify whether CPF is a hamartomatous,
      neoplastic, or reparative process, it demonstrated active participation of the
      surface endothelial lining cells with excessive formation of basal membrane
      material in the formation of CPF.

PMID- 7567941
TI  - Keratin 19 in paraffin sections of medullary carcinoma and other benign and
      malignant breast lesions.
AB  - This investigation was aimed at studying the distribution of keratin 19 in
      various histological types of invasive breast carcinoma and benign breast lesions
      using two different antibodies, comparing the results, and assessing the
      significance of the finding. In particular, the usefulness of using the absence
      of keratin 19 immunostaining as a marker for medullary carcinoma was examined.
      Paraffin sections of 49 invasive breast carcinomas and 40 benign lesions were
      examined by the avidin-biotin complex immunoperoxidase technique using two
      commercially available keratin 19-specific monoclonal antibodies, BA17 and RCK
      108. The results showed that the latter antibody stained more cases and the
      intensity of its staining was more pronounced than BA17. Most medullary and
      poorly differentiated invasive ductal carcinomas were BA17 negative and RCK108
      negative or weakly positive. Moderately and well-differentiated ductal, invasive
      lobular, tubular, and most mucinous carcinomas were mostly positive with both
      antibodies, whereas a case of signet ring and a case of spindle cell carcinoma
      were negative with the two antibodies. Thirty eight of the 40 benign lesions
      examined showed variable numbers of positive cells, reflecting in general the
      pattern seen in normal ducts and acini. It is concluded that although keratin 19
      seems to be completely absent or at most only weakly represented in paraffin
      sections of medullary carcinoma, similar reactions are obtained with poorly
      differentiated ductal tumors. Different antibodies may give different reactions,
      but well-differentiated ductal and invasive lobular tumors are usually more
      strongly stained, whereas signet ring and spindle cell carcinomas seem to be
      negative.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567940
TI  - Postmenopausal squamous atypia: a spectrum including "pseudo-koilocytosis".
AB  - In addition to typical atrophy, the postmenopausal cervix may exhibit a spectrum
      of epithelial and cellular alterations, including prominent perinuclear halos,
      nuclear hyperchromasia, variation in nuclear size, and multinucleation. It has
      not been determined whether such changes, termed postmenopausal squamous atypia
      (PSA), represent age-related epithelial disturbances or human papillomavirus
      (HPV)-related low-grade squamous intraepithelial lesions (condyloma). We surveyed
      30 cervical biopsies from 26 women over the age of 50 that contained cytoplasmic
      halos and a spectrum of nuclear alterations, either alone or in association with
      atrophy. Twenty-three exhibited epithelium with 2- to 3-fold nuclear enlargement,
      and 18 had moderate or marked nuclear staining intensity. Eleven had a maximum of
      one or more multinucleated cells in a high-power field. Despite the nuclear
      alterations, none of the biopsies were positive for HPV by PCR analysis. This is
      in contrast to 104 of 141 low- and high-grade squamous intraepithelial lesions
      from a wide age range of women analyzed in the same manner (P = .000006).
      Features distinguishing PSA from HPV-associated low-grade squamous
      intraepithelial lesions (condyloma) included less variation in nuclear size and
      staining intensity, more finely and evenly distributed nuclear chromatin, and
      greater uniformity of perinuclear halos in PSA. In menopausal or postmenopausal
      women, PSA should be excluded when considering the diagnosis of a low-grade
      squamous intraepithelial lesion, specifically if the diagnosis rests on the
      interpretation of koilocytotic atypia.

PMID- 7567942
TI  - Angiomatous lesions in the wall of chronic pyothorax.
AB  - Formation of massive hematoma in the cavity of chronic pyothorax (CP) has been
      described previously, but its mechanism remained unclear. In the present study of
      99 cases, the vascular lesions in the wall of CP were examined by histological
      methods, including immunohistochemistry. The age of patients ranged from 42 to 80
      years (mean 57 years), with a male to female ratio of 3.3. Histologically the CP
      wall was covered by a fibrin layer containing cellular debris and red blood
      cells. Directly beneath the fibrin layer, a fibrous layer of varied thickness was
      present that extended to the subserosal tissue or so-called fat plane defined by
      computed tomography. At the junctional region between the fibrin and fibrous
      layer, angiomatous lesions were observed in 33 cases (Group I). In the fibrin
      layer of this group, dilated vessels frequently bulged into the pleural cavity.
      In another two cases, closely packed large vessels with irregularly thickened
      walls resembled an arteriovenous fistula (Group II). In seven patients,
      histologic specimens showed a total necrosis. The remaining 57 cases without the
      findings in Groups I and II were categorized as Group III. These findings
      suggested that formation of angiomatous lesion preceed intrapleural bleeding,
      which occasionally progressed to form a massive hematoma.

PMID- 7567943
TI  - Sinonasal intestinal-type adenocarcinoma: immunohistochemical profile and
      comparison with colonic adenocarcinoma.
AB  - Sinonasal intestinal-type adenocarcinomas (ITAC), as their name implies, bear a
      striking resemblance to primary intestinal neoplasia. The value and limitations
      of immunohistochemistry in making this distinction have not been previously
      defined. We determined the immunohistochemical staining profile of 12 sinonasal
      ITAC and compared their staining with that of 12 histologically similar colonic
      adenocarcinomas. All ITAC stained for cytokeratin and epithelial membrane
      antigen. Additional positive reactions were as follows: B72.3, 11 of 12; Ber EP4,
      11 of 12; Leu M1, 8 of 12; HMFG-2, 12 of 12; and BRST-1, weak staining in seven
      of 12 cases. All 12 ITAC were negative for vimentin, synaptophysin, and actin.
      Colonic carcinomas stained similarly for these markers. Three additional antigens
      differed in their expression in ITAC versus colonic tumors. Carcinoembryonic
      antigen was strongly present in only two of 12 ITAC, with focal positivity in six
      of 12 and no staining in four of 12 cases. In contrast, all 12 colonic
      adenocarcinomas were strongly positive for carcinoembryonic antigen. Chromogranin
      positive cells were present and often numerous in nine of 12 ITAC, in contrast to
      only rare positive cells in three of 12 colonic tumors. Neuron-specific enolase
      was present in five of 12 ITAC but was absent from all colonic tumors studied.
      ITAC are less often and less strongly carcinoembryonic-antigen positive and more
      prone to exhibit divergent neuroendocrine differentiation. These features may be
      of some value in distinguishing ITAC and colonic metastases. Neuroendocrine
      differentiation in ITAC was associated with higher mortality. Of the five
      patients with ITAC having 1+ to 2+ chromogranin positivity, only one was free of
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567945
TI  - Blood parameters associated with atherogenic and thrombogenic risk in smokers and
      nonsmokers with similar life-styles.
AB  - Current evidence indicates that life-style factors can affect the risk of
      developing cardiovascular disease. The life-style of cigarette smokers, as a
      group, differs in many ways from that of nonsmokers. Most studies that compare
      clinical pathologic findings related to atherogenic and thrombogenic risk in
      smokers and nonsmokers do not adequately control for most of the life-style
      differences between these two groups. In this study, a number of atherogenic risk
      factors (cholesterol, low-density lipoprotein, high-density lipoprotein, very low
      density lipoprotein, high-density lipoprotein/cholesterol, triglycerides, and
      glucose) and thrombogenic risk factors (total white blood cell count, total red
      blood cell count; percent of monocytes, lymphocytes, neutrophils, basophils, and
      eosinophils; interleukin-1, leukotriene B4, hematocrit, hemoglobin, bilirubin,
      mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean
      corpuscular volume, platelet count, prothrombin time, partial thromboplastin
      time, and fibrinogen) were compared in male and female cigarette smokers and non
      smokers who were selected to have approximately similar self-reported life-styles
      (i.e., food, alcohol, and vitamin consumption and exercise level). However, the
      smokers (male and female) consumed more coffee (P < 0.05) than the nonsmokers. A
      trend toward blue-collar versus white collar occupational status was also
      observed in the male smokers relative to male nonsmokers. Cigarette consumption
      and urinary cotinine and carboxyhemoglobin levels did not differ between male and
      female smokers. Atherogenic and thrombogenic values were determined from venous
      blood samples. No statistically significant (P > 0.05) differences in clinical
      pathologic findings related to atherogenic risk were observed between the smokers
      and nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567944
TI  - Secondary tumors of the gastrointestinal tract: surgical pathologic findings and
      comparison with autopsy survey.
AB  - Secondary tumors of the gastrointestinal (GI) tract are unusual but are probably
      more common than clinically suspected. Comparison of surgical pathologic findings
      and autopsy experience over a 14-yr period revealed a different spectrum of
      tumors, which may reflect clinical practice issues and the pathophysiology of
      individual tumors. Seventy-three surgical resection or biopsy cases with
      clinically evident secondary tumors were compared with 108 autopsy cases with
      secondary malignancies involving the GI tract. The most common tumors in surgical
      specimens were melanoma (22 cases), ovary (11 cases), bladder (eight cases),
      breast (six cases), and lung (five cases). The most common primary tumors at
      autopsy were lung (21 cases), gynecologic malignancies (18 cases), breast (14
      cases), and pancreas (nine cases). In most cases, routine histologic examination
      yielded clues to the primary tumor. Metastatic breast carcinoma cases had a high
      potential for misinterpretation because most metastases consisted of infiltrating
      strands of pleomorphic cells without gland formation. Signet ring cells were
      present in most metastases (all six surgical cases and seven of 14 autopsies),
      regardless of the histologic type of the primary breast carcinoma. The time from
      diagnosis of the primary tumor to development of GI involvement varied widely,
      from presentation with GI metastases to more than 30 yr for metastatic malignant
      melanoma. Survival after development of GI involvement was generally poor, with
      most patients surviving less than 1 yr. However, long-term palliation may be
      achieved in a small subset of patients, chiefly those with single small bowel
      deposits of malignant melanoma or patients with breast carcinoma responsive to
      tamoxifen.

PMID- 7567947
TI  - Neonatal Escherichia coli infection and segmental arterial necrosis: similarity
      to edema disease of weanling swine.
AB  - A 32-wk gestation female patient had Escherichia coli pneumonia, hyaline
      membranes, and pulmonary hemorrhage and died 20 h after birth. E. coli was
      cultured from the placenta and from both lungs at autopsy. In the lungs and other
      organs, bland segmental necrosis of the wall of small arteries and arterioles was
      observed. It was morphologically indistinguishable from that seen in naturally
      occurring and experimentally induced edema disease of swine, which suggests both
      conditions may share a common pathogenesis. In swine, the disease is caused by
      Shiga-like enterotoxin-producing E. coli. To our knowledge, this is the first
      documentation of edema disease-like arterial lesions in humans.

PMID- 7567948
TI  - Immunohistochemical evaluation of E-cadherin and epidermal growth factor receptor
      in non-small cell lung cancer.
AB  - Enhanced expression of the epidermal growth factor receptor and loss of
      expression of the cell-cell adhesion molecule E-cadherin have each been
      implicated in the development and progression of a variety of human malignancies.
      There is some evidence for a correlation between the expression of these two
      genes and the possible influence of the E-cadherin gene product on the expression
      of epidermal growth factor receptor. We evaluated 33 matched primary and
      metastatic non-small cell lung cancer specimens using immunohistochemical
      staining. There was a statistically significant correlation between staining
      intensity for epidermal growth factor receptor and E-cadherin in the primary
      tumors (P = 0.017, by Spearman correlation test). No difference was noted between
      primary and metastatic disease for either gene product. Studies that include
      clinical data are needed to clarify the significance of these findings and to
      evaluate whether these markers will help predict prognosis in tumors.

PMID- 7567946
TI  - p53 gene status in endometrial carcinomas showing diffuse positivity for p53
      protein by immunohistochemical analysis.
AB  - Although detection of p53 protein by immunohistochemical testing was originally
      thought to indicate p53 gene mutation, recent analyses of human malignancies have
      shown that high expression of p53 protein may occur without detectable gene
      mutation. Several explanations have been proposed for this phenomenon, including
      mutation out of "hot spot" regions, overexpression of wild-type protein, sampling
      error in molecular analyses, and conformational changes of wild-type p53 protein.
      As discussed, it is unlikely that the first two possibilities contribute
      significantly to the occurrence of this phenomenon, and the current study
      examined the possibility that sampling error in molecular analyses might account
      for a lack of concordance between immunohistochemical and molecular analyses.
      Such a possibility exists because immunohistochemical studies frequently report
      high expression when staining is only focal or regional and molecular analyses
      are based on the polymerase chain reaction, which is highly exponential in nature
      and may not detect mutation if the target gene segment is not amplified early in
      the chain reaction. In the current report, p53 protein expression was examined by
      immunohistochemical testing in 45 cases of endometrioid carcinoma, and all cases
      showing diffuse positivity were then examined by polymerase chain reaction in
      combination with single-strand conformational analysis for exons 4 to 9 with the
      use of a microdissection technique to separate malignant from benign cells. Of
      the 45 cases, diffuse staining was found in four cases, and only two of the four
      were found to show evidence of gene mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567949
TI  - Ideas in pathology. Whose tumor is this? FISHing for the answer.
AB  - Errors in tissue handling and accessioning during procurement as well as in the
      laboratory occasionally occur; rarely these errors may result in specimen
      misidentification and therefore misdiagnosis. Tissue "pick-ups" or "floaters" are
      difficult to avoid in large, busy histology laboratories. While misidentification
      problems can usually be sorted out based on clinical history, they are
      occasionally problematic. We report two misidentified cases that presented to the
      Gastrointestinal Pathology Division at the Johns Hopkins Hospital and a novel
      method that was used to correctly solve the problem.

PMID- 7567950
TI  - A consensus prediction of the secondary structure for the 6-phospho-beta-D
      galactosidase superfamily.
AB  - Two separate unrefined models for the secondary structure of two subfamilies of
      the 6-phospho-beta-D-galactosidase superfamily were independently constructed by
      examining patterns of variation and conservation within homologous protein
      sequences, assigning surface, interior, parsing, and active site residues to
      positions in the alignment, and identifying periodicities in these. A consensus
      model for the secondary structure of the entire superfamily was then built. The
      prediction tests the limits of an unrefined prediction made using this approach
      in a large protein with substantial functional and sequence divergence within the
      family. The protein belongs to the (alpha-beta class), with the core beta strands
      aligned parallel. The supersecondary structural elements that are readily
      identified in this model is a parallel beta sheet built by strands C, D, and E,
      with helices 2 and 3 connecting strands (C+D) and (D+E), respectively, and an
      analogous beta-alpha unit (strand G and helix 7) toward the end of the sequence.
      The resemblance of the supersecondary model to the tertiary structure formed by 8
      fold alpha-beta barrel proteins is almost certainly not coincidental.

PMID- 7567952
TI  - A lipoamide dehydrogenase from Neisseria meningitidis has a lipoyl domain.
AB  - A protein of molecular weight of 64 kDa (p64k) found in the outer membrane of
      Neisseria meningitidis shows a high degree of homology with both the lipoyl
      domain of the acetyltransferase and the entire sequence of the lipoamide
      dehydrogenase, the E2 and E3 components of the dehydrogenase multienzyme
      complexes, respectively. The alignment of the p64k with lipoyl domains and
      lipoamide dehydrogenases from different species is presented. The possible
      implications of this protein in binding protein-dependent transport are
      discussed. This is the first lipoamide dehydrogenase reported to have a lipoyl
      domain.

PMID- 7567951
TI  - Long timestep dynamics of peptides by the dynamics driver approach.
AB  - Previous experience with the Langevin/implicit-Euler scheme for dynamics ("LI")
      on model systems (butane, water) has shown that LI is numerically stable for
      timesteps in the 5-20 fs range but quenches high-frequency modes. To explore
      applications to polypeptides, we apply LI to model systems (several dipeptides, a
      tetrapeptide, and a 13-residue oligoalanine) and also develop a new dynamics
      driver approach ("DA"). The DA scheme, based on LI, addresses the important issue
      of proper sampling, which is unlikely to be solved by small-timestep integration
      methods or implicit methods with intrinsic damping at room temperature, such as
      LI. Equilibrium averages, time-dependent molecular properties, and sampling
      trends at room temperature are reported for both LI and DA dynamics simulations,
      which are then compared to those generated by a standard explicit discretization
      of the Langevin equation with a 1 fs timestep. We find that LI's quenching
      effects are severe on both the fast and slow (due to vibrational coupling)
      frequency modes of all-atom polypeptides and lead to more restricted dynamics at
      moderate timesteps (40 fs). The DA approach empirically counteracts these damping
      effects by adding random atomic perturbations to the coordinates at each step
      (before the minimization of a dynamics function). By restricting the energetic
      fluctuations and controlling the kinetic energy, we are able with a 60 fs
      timestep to generate continuous trajectories that sample more of the relevant
      conformational space and also reproduce reasonably Boltzmann statistics. Although
      the timescale for transition may be accelerated by the DA approach, the
      transitional information obtained for the alanine dipeptide and the tetrapeptide
      is consistent with that obtained by several other theoretical approaches that
      focus specifically on the determination of pathways. While the trajectory for
      oligoalanine by the explicit scheme over the nanosecond timeframe remains in the
      vicinity of the full alpha R-helix starting structure, and a high-temperature
      (600 degrees K) MD trajectory departs slowly from the alpha helical structure,
      the DA-generated trajectory for the same CPU time exhibits unfolding and
      refolding and reveals a range of conformations with an intermediate helix
      content. Significantly, this range of states is more consistent with
      spectroscopic experiments on small peptides, as well as the cooperative two-state
      model for helix-coil transition. The good, near-Boltzmann statistics reported for
      the smaller systems above, in combination with the interesting oligoalanine
      results, suggest that DA is a promising tool for efficiently exploring
      conformational spaces of biomolecules and exploring folding/unfolding processes
      of polypeptides.

PMID- 7567953
TI  - Knowledge-based modeling of the D-lactate dehydrogenase three-dimensional
      structure.
AB  - A three-dimensional structure of the NAD-dependent D-lactate dehydrogenase of
      Lactobacillus bulgaricus is modeled using the structure of the formate
      dehydrogenase of Pseudomonas sp. as template. Both sequences share only 22% of
      identical residues. Regions for knowledge-based modeling are defined from the
      structurally conserved regions predicted by multiple alignment of a set of
      related protein sequences with low homology. The model of the D-LDH subunit
      shows, as for the formate dehydrogenase, an alpha/beta structure, with a
      catalytic domain and a coenzyme binding domain. It points out the catalytic
      histidine (His-296) and supports the hypothetical catalytic mechanism. It also
      suggests that the other residues involved in the active site are Arg-235,
      possibly involved in the binding of the carboxyl group of the pyruvate, and Phe
      299, a candidate for stabilizing the methyl group of the substrate.

PMID- 7567954
TI  - A novel approach to predicting protein structural classes in a (20-1)-D amino
      acid composition space.
AB  - The development of prediction methods based on statistical theory generally
      consists of two parts: one is focused on the exploration of new algorithms, and
      the other on the improvement of a training database. The current study is devoted
      to improving the prediction of protein structural classes from both of the two
      aspects. To explore a new algorithm, a method has been developed that makes
      allowance for taking into account the coupling effect among different amino acid
      components of a protein by a covariance matrix. To improve the training database,
      the selection of proteins is carried out so that they have (1) as many non
      homologous structures as possible, and (2) a good quality of structure. Thus, 129
      representative proteins are selected. They are classified into 30 alpha, 30 beta,
      30 alpha + beta, 30 alpha/beta, and 9 zeta (irregular) proteins according to a
      new criterion that better reflects the feature of the structural classes
      concerned. The average accuracy of prediction by the current method for the 4 x
      30 regular proteins is 99.2%, and that for 64 independent testing proteins not
      included in the training database is 95.3%. To further validate its efficiency, a
      jackknife analysis has been performed for the current method as well as the
      previous ones, and the results are also much in favor of the current method. To
      complete the mathematical basis, a theorem is presented and proved in Appendix A
      that is instructive for understanding the novel method at a deeper level.

PMID- 7567955
TI  - Purification, crystallization, and preliminary X-ray diffraction analyses of the
      bacterial chemotaxis receptor modifying enzymes.
AB  - Bacterial chemotaxis receptor modifying enzymes from Salmonella typhimurium have
      been crystallized using microseeding techniques. The crystals of the S-adenosyl-L
      methionine-dependent methyltransferase, CheR, belong to the monoclinic space
      group P21 with cell constants a = 55.1 A, b = 48.1 A, c = 63.1 A, beta = 112.3
      degrees. The crystals of the catalytic domain of the methylesterase, CheB, belong
      to the trigonal space group P3(2)21 or P3(1)21 with unit cell dimensions of a = b
      = 63.4 A, c = 86.8 A. Both crystals contain one molecule per asymmetric unit and
      have calculated Matthews' volumes of 2.4 A3/Da.

PMID- 7567956
TI  - Crystallization and preliminary X-ray diffraction studies of a bacterial
      flavohemoglobin protein.
AB  - A flavohemoglobin protein (FHP) was isolated from Alcaligenes eutrophus and has
      been crystallized by vapor diffusion methods using PEG 3350 as precipitant. The
      crystals of the FAD- and heme-containing protein belong to the monoclinic space
      group P2(1) with unit cell parameters of 52.2 A, 85.8 A, 103.9 A, and 81.8
      degrees corresponding to two molecules per asymmetric unit. The crystals diffract
      at least to a resolution of 2.0 A and are suitable for an X-ray structure
      analysis.

PMID- 7567957
TI  - Crystallization and preliminary X-ray investigation of the recombinant
      Trypanosoma brucei rhodesiense calmodulin.
AB  - Bipyramidal crystals of the recombinant calmodulin from Trypanosoma brucei
      rhodesiense were obtained by vapor diffusion against 55% (v/v) 2-methyl-2,4
      pentanediol in 0.05 M cacodylate buffer, pH 5.6. When few nucleation events
      occurred, crystals grew to 0.25 x 0.25 x 1.20 mm. The space group of the crystal
      is I4(1)22, with unit cell dimensions a = b = 56.88 A, c = 230.11 A, alpha = beta
      = gamma = 90 degrees, z = 16. The molecular mass and volume of the unit cell
      suggest that there is one molecule in the asymmetric unit. The I/sigma (I) ratio
      for data at 3.0 A resolution was 3.67, indicating that the final structure can be
      refined at higher resolution. Molecular replacement methods and the PC-refinement
      technique have not yet yielded the structure under a variety of search
      conditions. We are currently investigating the multiple isomorphous replacement
      approach to determine this crystal structure.

PMID- 7567958
TI  - Accurate general method for lattice approximation of three-dimensional structure
      of a chain molecule.
AB  - An algorithm based on dynamic programming gives the lattice models having the
      minimal RMS deviations from the actual folds of protein (RNA, etc.) chains for a
      given lattice and a given orientation of the macromolecule relative to the
      lattice. The algorithm is applicable for 3-D lattices of any kind. The accuracy
      of the lattice approximation increases when the distance between neighbor chain
      links is not rigidly fixed. Special repulsive potentials facilitate generation of
      self-avoiding lattice chains. The results of model building show the efficiency
      and precision of this proposed general method when compared with others.

PMID- 7567960
TI  - An analysis of side chain interactions and pair correlations within antiparallel
      beta-sheets: the differences between backbone hydrogen-bonded and non-hydrogen
      bonded residue pairs.
AB  - Cross-strand pair correlations are calculated for residue pairs in anti-parallel
      beta-sheet for two cases: pairs whose backbone atoms are hydrogen bonded together
      (H-bonded site) and pairs which are not (non-H-bonded site). The statistics show
      that this distinction is important. When glycine is located on the edge of a
      sheet, it shows a 3:1 preference for the H-bonded site. The strongest observed
      correlations are for pairs of disulfide-bonded cystines, many of which adopt a
      close-packed conformation with each cystine in a spiral conformation of opposite
      chirality to its partner. It is likely that these pairs are a signature for the
      family of small, cystine-rich proteins. Most other strong positive and negative
      correlations involve charged and polar residues. It appears that electrostatic
      compatibility is the strongest factor affecting pair correlation. Significant
      correlations are observed for beta- and gamma-branched residues in the non-H
      bonded site. An examination of the structures shows a directionality in side
      chain packing. There is a correlation between (1) the directionality in the
      packing interactions of non-H-bonded beta- and gamma-branched residue pairs, (2)
      the handedness of the observed enantiomers of chiral beta-branched side chains,
      and (3) the handedness of the twist of beta-sheet. These findings have
      implications for the formation of beta-sheets during protein folding and the
      mechanism by which the sheet becomes twisted.

PMID- 7567959
TI  - Investigation of the folding pathway of the TEM-1 beta-lactamase.
AB  - The TEM-1 beta-lactamase is a globular protein containing 12 proline residues.
      The folding mechanism of this enzyme was investigated by kinetic and equilibrium
      experiments with the help of fluorescence spectroscopy and circular dichroism.
      The equilibrium denaturation of the protein induced by guanidine hydrochloride
      occurs in two discrete steps, indicating the existence of a thermodynamically
      stable intermediate state. This state is 5.2 +/- 0.4 kcal/mol less stable than
      the native conformation and 5.7 +/- 0.2 kcal/mol more stable than the fully
      denatured protein. This intermediate state exhibits a high content of native
      secondary structure elements but is devoid of specific tertiary organization; its
      relation to the "molten globule" is discussed. Refolding kinetic experiments
      revealed the existence of a transient intermediate conformation between the
      thermodynamically stable intermediate and the native protein. This transient
      intermediate appears rapidly during the folding reaction. It exhibits a secondary
      structure content very similar to that of the native protein and has also
      recovered a significant amount of tertiary organisation. The final refolding step
      of the TEM-1 beta-lactamase, leading to the native enzyme, is dominated by two
      major slow kinetic phases which probably reflect a very complex process
      kinetically limited by proline cis/trans isomerization.

PMID- 7567963
TI  - Molecular dynamics simulations of rubredoxin from Clostridium pasteurianum:
      changes in structure and electrostatic potential during redox reactions.
AB  - Molecular dynamics simulations of Clostridium pasteurianum rubredoxin in the
      oxidized and reduced forms have been performed. Good agreement between both forms
      and crystal data has been obtained (rms deviation of backbone atoms of 1.06 and
      1.42 A, respectively), which was due in part to the use of explicit solvent and
      counterions. The reduced form exhibits an unexpected structural change: the redox
      site becomes much more solvent-accessible, so that water enters a channel between
      the surface and the site, but with little actual structural rearrangement (the
      rms deviation of backbone atoms between the oxidized and reduced is 0.77 A). The
      increase in solvent accessibility is also seen, although to a much lesser extent,
      between the oxidized and reduced crystal structures of Pyrococcus furiosus
      rubredoxin, but no high resolution crystal or nuclear magnetic resonance solution
      data exist for reduced C. pasteurianum rubredoxin. The electrostatic potential at
      the iron site and fluctuations in the potential, which contribute to both the
      redox and electron transfer properties, have also been evaluated for both the
      oxidized and the reduced simulations. These results show that the backbone plays
      a significant role (62-70 kcal/mol/e) and the polar side chains contribute
      relatively little (0-4 kcal/mol/e) to the absolute electrostatic potential at the
      iron of rubredoxin for both forms. However, both groups contribute significantly
      to the change in redox state by becoming more polarized and more densely packed
      around the redox site upon reduction. Furthermore, these results show that the
      solvent becomes much more polarized in the reduced form than in the oxidized
      form, even excluding the penetrating water. Finally, the simulation indicates
      that the contribution of the charged side chains to the electrostatic potential
      is largely canceled by that of the counterions.

PMID- 7567961
TI  - Empirical evaluation of the influence of side chains on the conformational
      entropy of the polypeptide backbone.
AB  - Changes in amino acid side chains have long been recognized to alter the range
      and distribution of phi, psi angles found in the main chain of polypeptides.
      Altering the range and distribution of phi, psi angles also alters the
      conformational entropy of the flexible denatured state and may thus stabilize or
      destabilize it relative to the comparatively conformationally rigid native state.
      A database of 12,320 residues from 61 nonhomologous, high resolution crystal
      structures was examined to determine the phi, psi conformational preferences of
      each of the 20 amino acids. These observed distributions in the native state of
      proteins are assumed to also reflect the distributions found in the denatured
      state. The distributions were used to approximate the energy surface for each
      residue, allowing the calculation of relative conformational entropies for each
      residue relative to glycine. In the most extreme case, replacement of glycine by
      proline, conformational entropy changes will stabilize the native state relative
      to the denatured state by -0.82 +/- 0.08 kcal/mol at 20 degrees C. Surprisingly,
      alanine is found to be the most ordered residue other than proline. This
      unexpected result is a result of the high percentage of alanines found in helical
      conformations. This either indicates that the observed distributions in the
      native state do not reflect the distributions in the denatured state, or that
      alanine is much more likely to adopt a helical conformation in the denatured
      state than residues with longer side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7567962
TI  - Insulin and epidermal growth factor receptors contain the cysteine repeat motif
      found in the tumor necrosis factor receptor.
AB  - The insulin receptor (INSR) and epidermal growth factor receptor (EGFR) are
      representatives of two structurally related subfamilies of tyrosine kinase
      receptors. Using the Wisconsin GCG sequence analysis programs, we have
      demonstrated that the cysteine-rich regions of INSR and EGFR conform to the
      structural motif found in the tumor necrosis factor receptor (TNFR) family. The
      study also revealed that these regions were not composed of simple repeats of
      eight cysteine residues as previously proposed and that the second Cys-rich
      region of EGFR contained one fewer TNFR repeat than the first. The sequence
      alignments identified two cysteine residues in INSR that could be responsible for
      the additional disulfide bonds known to be involved in dimer formation. The
      published data on the alignments for the fibronectin type III repeat region of
      the INSR together with previous cysteine mutagenesis studies indicated that there
      were two disulfide bonds linking the alpha and beta chains of the INSR, but only
      one alpha-beta linkage in the insulin-like growth factor 1 receptor (IG1R).
      Database searches and sequence alignments showed that the TNFR motif is also
      found in the cysteine-rich repeats of laminins and the noncatalytic domains of
      furin-like proteases. If the starting position of the repeat is altered the
      characteristic laminin repeat of eight cysteine residues can be shown to consist
      of a TNFR-like motif fused to the last half of an EGF-like repeat. The
      overlapping regions of these two motifs are known to have identical disulfide
      bonding patterns and similar protein folds.

PMID- 7567964
TI  - Exploring the binding preferences/specificity in the active site of human
      cathepsin E.
AB  - Aspartic proteinases are produced in the human body by a variety of cells. Some
      of these proteins, examples of which are pepsin, gastricsin, and renin, are
      secreted and exert their effects in the extracellular spaces. Cathepsin D and
      cathepsin E on the other hand are intracellular enzymes. The least characterized
      of the human aspartic proteinases is cathepsin E. Presented here are results of
      studies designed to characterize the binding specificities in the active site of
      human cathepsin E with comparison to other mechanistically similar enzymes. A
      peptide series based on Lys-Pro-Ala-Lys-Phe*Nph-Arg-Leu was generated to
      elucidate the specificity in the individual binding pockets with systematic
      substitutions in the P5-P2, and P2'-P3' based on charge, hydrophobicity, and
      hydrogen bonding. Also, to explore the S2 binding preferences, a second series of
      peptides based on Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu was generated with systematic
      replacements in the P2 position. Kinetic parameters were determined for both sets
      of peptides. The results were correlated to a rule-based structural model of
      human cathepsin E, constructed on the known three-dimensional structures of
      several highly homologous aspartic proteinases; porcine pepsin, bovine chymosin,
      yeast proteinase A, human cathepsin D, and mouse and human renin. Important
      specificity-determining interactions were found in the S3 (Glu-13) and S2 (Thr
      222, Gln-287, Leu-289, Ile-300) subsites.

PMID- 7567965
TI  - Comparison of the effects of hydrophobicity, amphiphilicity, and alpha-helicity
      on the activities of antimicrobial peptides.
AB  - Multiple linear regression was used to quantify the dependence of the
      antimicrobial activity of 13 peptides upon three calculated or experimentally
      determined parameters: mean hydrophobicity, mean hydrophobic moment, and alpha
      helix content. Mean hydrophobic moment is a measure of the amphiphilicity of
      peptides in an alpha-helical conformation. Antimicrobial activity was quantified
      as the reciprocal of the measured minimal inhibitory concentration (MIC) against
      Escherichia coli. One of the peptides was magainin 2, and the remainder were
      novel peptides designed for this study. The multiple linear regression results
      revealed that the amphiphilicity of the peptides was the most important factor
      governing antimicrobial activity compared to mean hydrophobicity or alpha-helix
      content. A better regression of the data was obtained using ln(1/MIC+constant) as
      the dependent variable than with either 1/MIC or ln(1/MIC). These results should
      be useful in designing peptides with higher antimicrobial activity.

PMID- 7567966
TI  - Crystallization and preliminary X-ray investigation of recombinant human
      interleukin 10.
AB  - Crystals of recombinant human interleukin 10 have been grown from solutions of
      ammonium sulfate. The crystals are tetragonal, space group P4(1)2(1)2 or
      P4(3)2(1)2; the unit cell axes are a = 36.5 A and c = 221.9 A. There is the
      equivalent of one polypeptide chain in the asymmetric unit. The crystals are
      stable to X-rays and diffract to at least 2.5 A resolution.

PMID- 7567967
TI  - Crystallization of UDP-N-acetylglucosamine O-acyltransferase from Escherichia
      coli.
AB  - Crystals of UDP-N-acetylglucosamine O-acyltransferase (lpxA) from Escherichia
      coli have been obtained from solutions of sodium/potassium phosphate and
      dimethylsulfoxide. These crystals belong to the cubic space group P2(1)3 (a =
      99.0 A), diffract X-rays to approximately 2.5 A resolution and contain one
      subunit of the enzyme in the asymmetric unit.

PMID- 7567968
TI  - Crystallization, characterization, and preliminary crystallographic studies of
      mitochondrial carbamoyl phosphate synthetase I of Rana catesbeiana.
AB  - Carbamoyl phosphate synthetase I (ammonia; E C 6.3.4.16) was purified from the
      liver of Rana catesbeiana (bullfrog). Crystals of the protein have been obtained
      at 22 degrees C by the hanging drop vapor diffusion technique, with polyethylene
      glycol as precipitant. Tetragonal crystals of about 0.3 x 0.3 x 0.7 mm diffract
      at room temperature to at least 3.5 A using a conventional source and are stable
      to X-radiation for about 12 h. Therefore, these crystals are suitable for high
      resolution studies. The space group is P4(1)2(1)2 (or its enantiomorph
      P4(3)2(1)2), with unit cell dimensions a = b = 291.6 A and c = 189.4 A. Density
      packing considerations are consistent with the presence of 4-6 monomers (M(r) of
      the monomer, 160,000) in the asymmetric unit. Amino-terminal sequence of the
      enzyme and of a chymotryptic fragment of 73.7 kDa containing the COOH-terminus
      has been obtained. The extensive sequence identity with rat and human carbamoyl
      phosphate synthetase I indicates the relevance for mammals of structural data
      obtained with the frog enzyme.

PMID- 7567969
TI  - LINUS: a hierarchic procedure to predict the fold of a protein.
AB  - We describe LINUS, a hierarchic procedure to predict the fold of a protein from
      its amino acid sequence alone. The algorithm, which has been implemented in a
      computer program, was applied to large, overlapping fragments from a diverse test
      set of 7 X-ray-elucidated proteins, with encouraging results. For all proteins
      but one, the overall fragment topology is well predicted, including both
      secondary and supersecondary structure. The algorithm was also applied to a
      molecule of unknown conformation, groES, in which X-ray structure determination
      is presently ongoing. LINUS is an acronym for Local Independently Nucleated Units
      of Structure. The procedure ascends the folding hierarchy in discrete stages,
      with concomitant accretion of structure at each step. The chain is represented by
      simplified geometry and folds under the influence of a primitive energy function.
      The only accurately described energetic quantity in this work is hard sphere
      repulsion--the principal force involved in organizing protein conformation
      [Richards, F. M. Ann. Rev. Biophys. Bioeng. 6:151-176, 1977]. Among other
      applications, the method is a natural tool for use in the human genome
      initiative.

PMID- 7567970
TI  - Modeling Lou Gehrig's disease in the fruit fly.

PMID- 7567971
TI  - In vivo regulation of muscle glycogen synthase and the control of glycogen
      synthesis.
AB  - The activity of glycogen synthase (GSase; EC 2.4.1.11) is regulated by covalent
      phosphorylation. Because of this regulation, GSase has generally been considered
      to control the rate of glycogen synthesis. This hypothesis is examined in light
      of recent in vivo NMR experiments on rat and human muscle and is found to be
      quantitatively inconsistent with the data under conditions of glycogen synthesis.
      Our first experiments showed that muscle glycogen synthesis was slower in non
      insulin-dependent diabetics compared to normals and that their defect was in the
      glucose transporter/hexokinase (GT/HK) part of the pathway. From these and other
      in vivo NMR results a quantitative model is proposed in which the GT/HK steps
      control the rate of glycogen synthesis in normal humans and rat muscle. The flux
      through GSase is regulated to match the proximal steps by "feed forward" to
      glucose 6-phosphate, which is a positive allosteric effector of all forms of
      GSase. Recent in vivo NMR experiments specifically designed to test the model are
      analyzed by metabolic control theory and it is shown quantitatively that the
      GT/HK step controls the rate of glycogen synthesis. Preliminary evidence favors
      the transporter step. Several conclusions are significant: (i) glucose
      transport/hexokinase controls the glycogen synthesis flux; (ii) the role of
      covalent phosphorylation of GSase is to adapt the activity of the enzyme to the
      flux and to control the metabolite levels not the flux; (iii) the quantitative
      data needed for inferring and testing the present model of flux control depended
      upon advances of in vivo NMR methods that accurately measured the concentration
      of glucose 6-phosphate and the rate of glycogen synthesis.

PMID- 7567972
TI  - Genetic bases for common polygenic diseases.

PMID- 7567973
TI  - Genetic determinants of human hypertension.
AB  - Hypertension is a common trait of multifactorial determination imparting an
      increased risk of myocardial infarction, stroke, and end-stage renal disease. The
      primary determinants of hypertension, as well as the factors which determine
      specific morbid sequelae, remain unknown in the vast majority of subjects.
      Knowledge that a large fraction of the interindividual variation in this trait is
      genetically determined motivates the application of genetic approaches to the
      identification of these primary determinants. Success in this effort will afford
      insights into pathophysiology, permit preclinical identification of subjects with
      specific inherited susceptibility, and provide opportunities to tailor therapy to
      specific underlying abnormalities. To date, mutations in three genes have been
      implicated in the pathogenesis of human hypertension: mutations resulting in
      ectopic expression of aldosterone synthase enzymatic activity cause a mendelian
      form of hypertension known as glucocorticoid-remediable aldosteronism; mutations
      in the beta subunit of the amiloride-sensitive epithelial sodium channel cause
      constitutive activation of this channel and the mendelian form of hypertension
      known as Liddle syndrome; finally, common variants at the angiotensinogen locus
      have been implicated in the pathogenesis of essential hypertension in Caucasian
      subjects, although the nature of the functional variants and their mechanism of
      action remain uncertain. These early findings demonstrate the feasibility and
      utility of the application of genetic analysis to dissection of this trait.

PMID- 7567975
TI  - Genetic analysis of type 1 diabetes using whole genome approaches.
AB  - Whole genome linkage analysis of type 1 diabetes using affected sib pair families
      and semi-automated genotyping and data capture procedures has shown how type 1
      diabetes is inherited. A major proportion of clustering of the disease in
      families can be accounted for by sharing of alleles at susceptibility loci in the
      major histocompatibility complex on chromosome 6 (IDDM1) and at a minimum of 11
      other loci on nine chromosomes. Primary etiological components of IDDM1, the HLA
      DQB1 and -DRB1 class II immune response genes, and of IDDM2, the minisatellite
      repeat sequence in the 5' regulatory region of the insulin gene on chromosome
      11p15, have been identified. Identification of the other loci will involve
      linkage disequilibrium mapping and sequencing of candidate genes in regions of
      linkage.

PMID- 7567974
TI  - Genetic dissection of Alzheimer disease, a heterogeneous disorder.
AB  - The genetics of Alzheimer disease (AD) are complex and not completely understood.
      Mutations in the amyloid precursor protein gene (APP) can cause early-onset
      autosomal dominant AD. In vitro studies indicate that cells expressing mutant
      APPs overproduce pathogenic forms of the A beta peptide, the major component of
      AD amyloid. However, mutations in the APP gene are responsible for 5% or less of
      all early-onset familial AD. A locus on chromosome 14 is responsible for AD in
      other early-onset AD families and represents the most severe form of the disease
      in terms of age of onset and rate of decline. Attempts to identify the AD3 gene
      by positional cloning methods are underway. At least one additional early-onset
      AD locus remains to be located. In late-onset AD, the apolipoprotein E gene
      allele epsilon 4 is a risk factor for AD. This allele appears to act as a dose
      dependent age-of-onset modifier. The epsilon 2 allele of this gene may be
      protective. Other late-onset susceptibility factors remain to be identified.

PMID- 7567977
TI  - Subunit-destabilizing mutations in Drosophila copper/zinc superoxide dismutase:
      neuropathology and a model of dimer dysequilibrium.
AB  - Mutations in Cu/Zn superoxide dismutase (SOD), a hallmark of familial amyotrophic
      lateral sclerosis (FALS) in humans, are shown here to confer striking
      neuropathology in Drosophila. Heterozygotes with one wild-type and one deleted
      SOD allele retain the expected 50% of normal activity for this dimeric enzyme.
      However, heterozygotes with one wild-type and one missense SOD allele show lesser
      SOD activities, ranging from 37% for a heterozygote carrying a missense mutation
      predicted from structural models to destabilize the dimer interface, to an
      average of 13% for several heterozygotes carrying missense mutations predicted to
      destabilize the subunit fold. Genetic and biochemical evidence suggests a model
      of dimer dysequilibrium whereby SOD activity in missense heterozygotes is reduced
      through entrapment of wild-type subunits into unstable or enzymatically inactive
      heterodimers. This dramatic impairment of the activity of wild-type subunits in
      vivo has implications for our understanding of FALS and for possible therapeutic
      strategies.

PMID- 7567979
TI  - Simian virus 40 late gene expression is regulated by members of the
      steroid/thyroid hormone receptor superfamily.
AB  - Transcription of the late genes of simian virus 40 (SV40) is repressed during the
      early phase of the lytic cycle of infection of binding of cellular factors,
      called IBP-s, to the SV40 late promoter; repression is relieved after the onset
      of viral DNA replication by titration of these repressors. Preliminary data
      indicated that one of the major components of IBP-s was human estrogen-related
      receptor 1 (hERR1). We show here that several members of the steroid/thyroid
      hormone receptor superfamily, including testis receptor 2, thyroid receptor alpha
      1 in combination with retinoid X receptor alpha, chicken ovalbumin upstream
      promoter transcription factors 1 and 2 (COUP-TF1 and COUP-TF2), as well as hERR1,
      possess the properties of IBP-s. These receptors bind specifically to hormone
      receptor binding sites present in the SV40 major late promoter. Recombinant COUP
      TF1 specifically represses transcription from the SV40 major late promoter in a
      cell-free transcription system. Expression of COUP-TF1, COUP-TF2, or hERR1 in
      monkey cells results in repression of the SV40 late promoter, but not the early
      promoter, in the absence of the virally encoded large tumor antigen.
      Overexpression of COUP-TF1 leads to a delay in the early-to-late switch in SV40
      gene expression during the lytic cycle of infection. Thus, members of this
      superfamily can play major direct roles in regulating expression of SV40.
      Possibly, natural or synthetic ligands to these receptors can serve as antiviral
      drugs. Our findings also provide the basis for the development of assays to
      screen for the ligands to testis receptor 2 and hERR1.

PMID- 7567978
TI  - D1 cap region involved in the receptor recognition and neural cell survival
      activity of human ciliary neurotrophic factor.
AB  - Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and
      differentiation of motor and other neurons, is a protein belonging structurally
      to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional
      structure modeling and site-directed mutagenesis to analyze its structure
      function relationship. The replacement of Lys-155 with any other amino acid
      residue resulted in abolishment of neural cell survival activity, and some of the
      Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap
      region (around the boundary between the CD loop and helix D) of hCNTF, including
      both Glu-153 and Lys-155, was shown to play a key role in the biological activity
      of hCNTF as one of the putative receptor-recognition sites. In this article, the
      D1 cap region of the 4-helix-bundle proteins is proposed to be important in
      receptor recognition and biological activity common to alpha-helical cytokine
      proteins reactive with gp130, a component protein of the receptors.

PMID- 7567976
TI  - The new dysmorphology: application of insights from basic developmental biology
      to the understanding of human birth defects.
AB  - Information obtained from studies of developmental and cellular processes in
      lower organisms is beginning to make significant contributions to the
      understanding of the pathogenesis of human birth defects, and it is now becoming
      possible to treat birth defects as inborn errors of development. Mutations in
      genes for transcription factors, receptors, cell adhesion molecules,
      intercellular junctions, molecules involved in signal transduction, growth
      factors, structural proteins, enzymes, and transporters have been identified in
      genetically caused human malformations and dysplasias. The identification of
      these mutations and the analysis of their developmental effects have been greatly
      facilitated by the existence of natural or engineered models in the mouse and
      even of related mutations in Drosophila, and in some instances a remarkable
      conservation of function in development has been observed, even between widely
      separated species.

PMID- 7567981
TI  - Mutational analysis of phytochrome B identifies a small COOH-terminal-domain
      region critical for regulatory activity.
AB  - Overexpression of phytochrome B (phyB) in transgenic Arabidopsis results in
      enhanced deetiolation in red light. To define domains of phyB functionally
      important for its regulatory activity, we performed chemical mutagenesis of a
      phyB-overexpressing line and screened for phenotypic revertants in red light.
      Four phyB-transgene-linked revertants that retain parental levels of full-length,
      dimeric, and spectrally normal overexpressed phyB were identified among 101 red
      light-specific revertants. All carry single amino acid substitutions in the
      transgene-encoded phyB that reduce activity by 40- to 1000-fold compared to the
      nonmutagenized parent. The data indicate that the mutant molecules are fully
      active in photosignal perception but defective in the regulatory activity
      responsible for signal transfer to downstream components. All four mutations fall
      within a 62-residue region in the COOH-terminal domain of phyB, with two
      independent mutations occurring in a single amino acid, Gly-767. Accumulating
      evidence indicates that the identified region is a critical determinant in the
      regulatory function of both phyB and phyA.

PMID- 7567980
TI  - Four p53 DNA-binding domain peptides bind natural p53-response elements and bend
      the DNA.
AB  - Recent structural studies of the minimal core DNA-binding domain of p53 (p53DBD)
      complexed to a single consensus pentamer sequence and of the isolated p53
      tetramerization domain have provided valuable insights into their functions, but
      many questions about their interacting roles and synergism remain unanswered. To
      better understand these relationships, we have examined the binding of the p53DBD
      to two biologically important full-response elements (the WAF1 and ribosomal gene
      cluster sites) by using DNA circularization and analytical ultracentrifugation.
      We show that the p53DBD binds DNA strongly and cooperatively with p53DBD to DNA
      binding stoichiometries of 4:1. For the WAF1 element, the mean apparent Kd is
      (8.3 +/- 1.4) x 10(-8) M, and no intermediate species of lower stoichiometries
      can be detected. We show further that complex formation induces an axial bend of
      at least 60 degrees in both response elements. These results, taken collectively,
      demonstrate that p53DBD possesses the ability to direct the formation of a tight
      nucleoprotein complex having the same 4:1 DNA-binding stoichiometry as wild-type
      p53 which is accompanied by a substantial conformational change in the response
      element DNA. This suggests that the p53DBD may play a role in the tetramerization
      function of p53. A possible role in this regard is proposed.

PMID- 7567982
TI  - Activation of Tsk and Btk tyrosine kinases by G protein beta gamma subunits.
AB  - Tsk/Itk and Btk are members of the pleckstrin-homology (PH) domain-containing
      tyrosine kinase family. The PH domain has been demonstrated to be able to
      interact with beta gamma subunits of heterotrimeric guanine nucleotide-binding
      proteins (G proteins) (G beta gamma) and phospholipids. Using cotransfection
      assays, we show here that the kinase activities of Tsk and Btk are stimulated by
      certain G beta gamma subunits. Furthermore, using an in vitro reconstitution
      assay with purified bovine brain G beta gamma subunits and the immunoprecipitated
      Tsk, we find that Tsk kinase activity is increased by G beta gamma subunits and
      another membrane factor(s). These results indicate that this family of tyrosine
      kinases could be an effector of heterotrimeric G proteins.

PMID- 7567983
TI  - RNA polymerase II/III transcription specificity determined by TATA box
      orientation.
AB  - The TATA box sequence in eukaryotes is located about 25 bp upstream of many genes
      transcribed by RNA polymerase II (Pol II) and some genes transcribed by RNA
      polymerase III (Pol III). The TATA box is recognized in a sequence-specific
      manner by the TATA box-binding protein (TBP), an essential factor involved in the
      initiation of transcription by all three eukaryotic RNA polymerases. We have
      investigated the recognition of the TATA box by the Pol II and Pol III basal
      transcription machinery and its role in establishing the RNA polymerase
      specificity of the promoter. Artificial templates were constructed that contained
      a canonical TATA box as the sole promoter element but differed in the orientation
      of the 8-bp TATA box sequence. As expected, Pol II initiated transcription in
      unfractionated nuclear extracts downstream of the "forward" TATA box. In distinct
      contrast, transcription that initiated downstream of the "reverse" TATA box was
      carried out specifically by Pol III. Importantly, this effect was observed
      regardless of the source of the DNA either upstream or downstream of the TATA
      sequence. These findings suggest that TBP may bind in opposite orientations on
      Pol II and Pol III promoters and that opposite, yet homologous, surfaces of TBP
      may be utilized by the Pol II and Pol III basal machinery for the initiation of
      transcription.

PMID- 7567985
TI  - Cortical activity flips among quasi-stationary states.
AB  - Parallel recordings of spike trains of several single cortical neurons in
      behaving monkeys were analyzed as a hidden Markov process. The parallel spike
      trains were considered as a multivariate Poisson process whose vector firing
      rates change with time. As a consequence of this approach, the complete recording
      can be segmented into a sequence of a few statistically discriminated hidden
      states, whose dynamics are modeled as a first-order Markov chain. The biological
      validity and benefits of this approach were examined in several independent ways:
      (i) the statistical consistency of the segmentation and its correspondence to the
      behavior of the animals; (ii) direct measurement of the collective flips of
      activity, obtained by the model; and (iii) the relation between the segmentation
      and the pair-wise short-term cross-correlations between the recorded spike
      trains. Comparison with surrogate data was also carried out for each of the above
      examinations to assure their significance. Our results indicated the existence of
      well-separated states of activity, within which the firing rates were
      approximately stationary. With our present data we could reliably discriminate
      six to eight such states. The transitions between states were fast and were
      associated with concomitant changes of firing rates of several neurons. Different
      behavioral modes and stimuli were consistently reflected by different states of
      neural activity. Moreover, the pair-wise correlations between neurons varied
      considerably between the different states, supporting the hypothesis that these
      distinct states were brought about by the cooperative action of many neurons.

PMID- 7567986
TI  - Isolation of cDNA clones encoding RICH: a protein induced during goldfish optic
      nerve regeneration with homology to mammalian 2',3'-cyclic-nucleotide 3'
      phosphodiesterases.
AB  - Using data derived from peptide sequencing of p68/70, a protein doublet induced
      during optic nerve regeneration in goldfish, we have isolated cDNAs that encode
      RICH (regeneration-induced CNPase homolog) from a goldfish regenerating retina
      cDNA library. The predicted RICH protein comprises 411 amino acids, possesses a
      pI of 4.48, and shows significant homology to the mammalian myelin marker enzyme
      2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; EC 3.1.4.37). The mRNA
      encoding RICH was demonstrated, by both Northern blot analysis and RNase
      protection assays, to be induced as much as 8-fold in regenerating goldfish
      retinas at 20 days after nerve crush. Analysis of total RNA samples from various
      tissues showed a broad distribution of RICH mRNA, with the highest levels
      observed in gravid ovary. The data obtained strongly suggest that RICH is
      identical or very similar to p68/70. The molecular cloning of RICH provides the
      means for a more detailed analysis of its function in nerve regeneration.
      Additionally, the homology of RICH and CNPase suggests that further investigation
      may provide additional insight into the role of these proteins in the nervous
      system.

PMID- 7567984
TI  - Inhibition of nuclear vesicle fusion by antibodies that block activation of
      inositol 1,4,5-trisphosphate receptors.
AB  - Inositol 1,4,5-trisphosphate (IP3) receptors are ligand-gated channels that
      release intracellular Ca2+ stores in response to the second messenger, IP3. We
      investigated the potential role of IP3 receptors during nuclear envelope assembly
      in vitro, using Xenopus egg extracts. Previous work suggested that Ca2+
      mobilization is required for nuclear vesicle fusion and implicated IP3 receptor
      activity. To test the involvement of IP3 receptors using selective reagents, we
      obtained three distinct polyclonal antibodies to the type 1 IP3 receptor.
      Pretreatment of membranes with two of the antibodies inhibited IP3-stimulated
      CA2+ release in vitro and also inhibited nuclear vesicle fusion. One inhibitory
      serum was directed against 420 residues within the "coupling" domain, which
      includes several potential regulatory sites. The other inhibitory serum was
      directed against 95 residues near the C terminus and identifies an inhibitory
      epitope(s) in this region. The antibodies had no effect on receptor affinity for
      IP3. Because nuclear vesicle fusion was inhibited by antibodies that block Ca2+
      flux, but not by control and preimmune antibodies, we concluded that the
      activation of IP3 receptors is required for fusion. The signal that activates the
      channel during fusion is unknown.

PMID- 7567989
TI  - Elongation factor 1 alpha concentration is highly correlated with the lysine
      content of maize endosperm.
AB  - Lysine is the most limiting essential amino acid in cereals, and for many years
      plant breeders have attempted to increase its concentration to improve the
      nutritional quality of these grains. The opaque2 mutation in maize doubles the
      lysine content in the endosperm, but the mechanism by which this occurs is
      unknown. We show that elongation factor 1 alpha (EF-1 alpha) is overexpressed in
      opaque2 endosperm compared with its normal counterpart and that there is a highly
      significant correlation between EF-1 alpha concentration and the total lysine
      content of the endosperm. This relationship is also true for two other cereals,
      sorghum and barley. It appears that genetic selection for genotypes with a high
      concentration of EF-1 alpha can significantly improve the nutritional quality of
      maize and other cereals.

PMID- 7567988
TI  - Postseptational chromosome partitioning in bacteria.
AB  - Mutations in the spoIIIE gene prevent proper partitioning of one chromosome into
      the developing prespore during sporulation but have no overt effect on
      partitioning in vegetatively dividing cells. However, the expression of spoIIIE
      in vegetative cells and the occurrence of genes closely related to spoIIIE in a
      range of nonsporulating eubacteria suggested a more general function for the
      protein. Here we show that SpoIIIE protein is needed for optimal chromosome
      partitioning in vegetative cells of Bacillus subtilis when the normal tight
      coordination between septation and nucleoid partitioning is perturbed or when
      septum positioning is altered. A functional SpoIIIE protein allows cells to
      recover from a state in which their chromosome has been trapped by a closing
      septum. By analogy to its function during sporulation, we suggest that SpoIIIE
      facilitates partitioning by actively translocating the chromosome out of the
      septum. In addition to enhancing the fidelity of nucleoid partitioning, SpoIIIE
      also seems to be required for maximal resistance to antibiotics that interfere
      with DNA metabolism. The results have important implications for our
      understanding of the functions of genes involved in the primary partitioning
      machinery in bacteria and of how septum placement is controlled.

PMID- 7567987
TI  - Aromatic-L-amino-acid decarboxylase, a pyridoxal phosphate-dependent enzyme, is a
      beta-cell autoantigen.
AB  - Different autoantigens are thought to be involved in the pathogenesis of insulin
      dependent diabetes mellitus, and they may account for the variation in the
      clinical presentation of the disease. Sera from patients with autoimmune
      polyendocrine syndrome type I contain autoantibodies against the beta-cell
      proteins glutamate decarboxylase and an unrelated 51-kDa antigen. By screening of
      an expression library derived from rat insulinoma cells, we have identified the
      51-kDa protein as aromatic-L-amino-acid decarboxylase (EC 4.1.1.28). In addition
      to the previously published full-length cDNA, forms coding for a truncated and an
      alternatively spliced version were identified. Aromatic L-amino acid
      decarboxylase catalyzes the decarboxylation of L-5-hydroxytryptophan to serotonin
      and that of L-3,4-dihydroxyphenylalanine to dopamine. Interestingly, pyridoxal
      phosphate is the cofactor of both aromatic L-amino acid decarboxylase and
      glutamate decarboxylase. The biological significance of the neurotransmitters
      produced by the two enzymes in the beta cells remains largely unknown.

PMID- 7567990
TI  - Retinoid X receptor alpha forms tetramers in solution.
AB  - Protein-protein interactions allow the retinoid X receptor (RXR) to bind to
      cognate DNA as a homo- or a heterodimer and to participate in mediating the
      effects of a variety of hormones on gene transcription. Here we report a
      systematic study of the oligomeric state of RXR in the absence of a DNA template.
      We have used electrophoresis under nondenaturing conditions and chemical
      crosslinking to show that in solution, RXR alpha forms homodimers as well as
      homotetramers. The dissociation constants governing dimer and tetramer formation
      were estimated by fluorescence anisotropy studies. The results indicate that RXR
      tetramers are formed with a high affinity and that at protein concentrations
      higher than about 70 nM, tetramers will constitute the predominant species.
      Tetramer formation may provide an additional level of the regulation of gene
      transcription mediated by RXRs.

PMID- 7567991
TI  - Peptide inhibitors of peptidyltransferase alter the conformation of domains IV
      and V of large subunit rRNA: a model for nascent peptide control of translation.
AB  - Peptides of 5 and 8 residues encoded by the leaders of attenuation regulated
      chloramphenicol-resistance genes inhibit the peptidyltransferase of
      microorganisms from the three kingdoms. Therefore, the ribosomal target for the
      peptides is likely to be a conserved structure and/or sequence. The inhibitor
      peptides "footprint" to nucleotides of domain V in large subunit rRNA when
      peptide-ribosome complexes are probed with dimethyl sulfate. Accordingly, rRNA
      was examined as a candidate for the site of peptide binding. Inhibitor peptides
      MVKTD and MSTSKNAD were mixed with rRNA phenol-extracted from Escherichia coli
      ribosomes. The conformation of the RNA was then probed by limited digestion with
      nucleases that cleave at single-stranded (T1 endonuclease) and double-stranded
      (V1 endonuclease) sites. Both peptides selectively altered the susceptibility of
      domains IV and V of 23S rRNA to digestion by T1 endonuclease. Peptide effects on
      cleavage by V1 nuclease were observed only in domain V. The T1 nuclease
      susceptibility of domain V of in vitro-transcribed 23S rRNA was also altered by
      the peptides, demonstrating that peptide binding to the rRNA is independent of
      ribosomal protein. We propose the peptides MVKTD and MSTSKNAD perturb
      peptidyltransferase center catalytic activities by altering the conformation of
      domains IV and V of 23S rRNA. These findings provide a general mechanism through
      which nascent peptides may cis-regulate the catalytic activities of translating
      ribosomes.

PMID- 7567992
TI  - De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin.
AB  - Caveolae are plasma membrane invaginations, which have been implicated in
      endothelial transcytosis, endocytosis, potocytosis, and signal transduction. In
      addition to their well-defined morphology, caveolae are characterized by the
      presence of an integral membrane protein termed VIP21-caveolin. We have recently
      observed that lymphocytes have no detectable VIP21-caveolin and lack plasma
      membrane invaginations resembling caveolae. Here we transiently express VIP21
      caveolin in a lymphocyte cell line using the Semliki Forest virus expression
      system and show de novo formation of plasma membrane invaginations containing
      VIP21-caveolin. These invaginations appear homogeneous in size and
      morphologically indistinguishable from caveolae of nonlymphoid cells. Moreover,
      the glycosylphosphatidylinositol-anchored protein. Thy1, patched by antibodies,
      redistributes to the newly formed caveolae. Our results show that VIP21-caveolin
      is a key structural component required for caveolar biogenesis.

PMID- 7567993
TI  - Identification of a viability domain in the granulocyte/macrophage colony
      stimulating factor receptor beta-chain involving tyrosine-750.
AB  - The granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor (GMR) is a
      heterodimeric receptor expressed by myeloid lineage cells. In this study we have
      investigated domains of the GMR beta-chain (GMR beta) involved in maintaining
      cellular viability. Using a series of nested GMR beta deletion mutants, we
      demonstrate that there are at least two domains of GMR beta that contribute to
      viability signals. Deletion of amino acid residues 626-763 causes a viability
      defect that can be rescued with fetal calf serum (FCS). Deletion of residues 518
      626, in contrast, causes a further decrement in viability that can be only
      partially compensated by the addition of FCS. GMR beta truncated proximal to
      amino acid 517 will not support long-term growth under any conditions. Site
      directed mutagenesis of tyrosine-750 (Y750), which is contained within the distal
      viability domain, to phenylalanine eliminates all demonstrable tyrosine
      phosphorylation of GMR beta. Cell lines transfected with mutant GMR beta (Y750-
      >F) have a viability disadvantage when compared to cell lines containing wild
      type GMR that is partially rescued by the addition of FCS. We studied signal
      transduction in mutant cell lines in an effort to identify pathways that might
      participate in the viability signal. Although tyrosine phosphorylation of JAK2,
      SHPTP2, and Vav is intact in Y750-->F mutant cell lines, Shc tyrosine
      phosphorylation is reduced. This suggests a potential role for Y750 and
      potentially Shc in a GM-CSF-induced signaling pathway that helps maintain
      cellular viability.

PMID- 7567995
TI  - A chloroplast lipoxygenase is required for wound-induced jasmonic acid
      accumulation in Arabidopsis.
AB  - Plant lipoxygenases are thought to be involved in the biosynthesis of lipid
      derived signaling molecules. The potential involvement of a specific Arabidopsis
      thaliana lipoxygenase isozyme, LOX2, in the biosynthesis of the plant growth
      regulators jasmonic acid (JA) and abscisic acid was investigated. Our
      characterization of LOX2 indicates that the protein is targeted to chloroplasts.
      The physiological role of this chloroplast lipoxygenase was analyzed in
      transgenic plants where cosuppression reduced LOX2 accumulation. The reduction in
      LOX2 levels caused no obvious changes in plant growth or in the accumulation of
      abscisic acid. However, the wound-induced accumulation of JA observed in control
      plants was absent in leaves of transgenic plants that lacked LOX2. Thus, LOX2 is
      required for the wound-induced synthesis of the plant growth regulator JA in
      leaves. We also examined the expression of a wound- and JA-inducible Arabidopsis
      gene, vsp, in transgenic and control plants. Leaves of transgenic plants lacking
      LOX2 accumulated less vsp mRNA than did control leaves in response to wounding.
      This result suggests that wound-induced JA (or some other LOX2-requiring
      component of the wound response pathway) is involved in the wound-induced
      regulation of this gene.

PMID- 7567994
TI  - Regulation of glycolipid synthesis in HL-60 cells by antisense
      oligodeoxynucleotides to glycosyltransferase sequences: effect on cellular
      differentiation.
AB  - Treatment of the human promyelocytic leukemia cell line HL-60 with antisense
      oligodeoxynucleotides to UDP-N-acetylgalactosamine:beta-1,4-N
      acetylgalactosaminyl-transferase (GM2-synthase; EC 2.4.1.92) and CMP-sialic
      acid:alpha-2,8-sialyltransferase (GD3-synthase; EC 2.4.99.8) sequences
      effectively down-regulated the synthesis of more complex gangliosides in the
      ganglioside synthetic pathways after GM3, resulting in a remarkable increase in
      endogenous GM3 with concomitant decreases in more complex gangliosides. The
      treated cells underwent monocytic differentiation as judged by morphological
      changes, adherent ability, and nitroblue tetrazolium staining. These data provide
      evidence that the increased endogenous ganglioside GM3 may play an important role
      in regulating cellular differentiation and that the antisense DNA technique
      proves to be a powerful tool in manipulating glycolipid synthesis in the cell.

PMID- 7567996
TI  - Cytochrome c oxidase in Neurospora crassa contains myristic acid covalently
      linked to subunit 1.
AB  - Radiolabel from [3H]myristic acid was incorporated by Neurospora crassa into the
      core catalytic subunit 1 of cytochrome c oxidase (EC 1.9.3.1), as indicated by
      immunoprecipitation. This modification of the subunit, which was specific for
      myristic acid, represents an uncommon type of myristoylation through an amide
      linkage at an internal lysine, rather than an N-terminal glycine. The
      [3H]myristate, which was chemically recovered from the radiolabeled subunit
      peptide, modified an invariant Lys-324, based upon analyses of proteolysis
      products. This myristoylated lysine is found within one of the predicted
      transmembrane helices of subunit 1 and could contribute to the environment of the
      active site of the enzyme. The myristate was identified by mass spectrometry as a
      component of mature subunit 1 of a catalytically active, purified enzyme. To our
      knowledge, fatty acylation of a mitochondrially synthesized inner-membrane
      protein has not been reported previously.

PMID- 7567997
TI  - A 20-nucleotide element in the intestinal fatty acid binding protein gene
      modulates its cell lineage-specific, differentiation-dependent, and cephalocaudal
      patterns of expression in transgenic mice.
AB  - A sequence of epithelial cell proliferation, allocation to four principal
      lineages, migration-associated differentiation, and cell loss occurs along the
      crypt-villus axis of the mouse intestine. The sequence is completed in a few days
      and is recapitulated throughout the life-span of the animal. We have used an
      intestine-specific fatty acid binding protein gene, Fabpi, as a model for
      studying regulation of gene expression in this unique developmental system.
      Promoter mapping studies in transgenic mice identified a 20-bp cis-acting element
      (5'-AGGTGGAAGCCATCACACTT-3') that binds small intestinal nuclear proteins and
      participates in the control of Fabpi's cephalocaudal, differentiation-dependent,
      and cell lineage-specific patterns of expression. Immunocytochemical studies
      using confocal and electron microscopy indicate that it does so by acting as a
      suppressor of gene expression in the distal small intestine/colon, as a
      suppressor of gene activation in proliferating and nonproliferating cells located
      in the crypts of Lieberkuhn, and as a suppressor of expression in the growth
      factor and defensin-producing Paneth cell lineage. The 20-bp domain has no
      obvious sequence similarities to known transcription factor binding sites. The
      three functions modulated by this compact element represent the types of
      functions required to establish and maintain the intestine's remarkably complex
      spatial patterns of gene expression. The transgenes described in this report also
      appear to be useful in characterizing the crypt's stem cell hierarchy.

PMID- 7567998
TI  - Erythropoiesis and globin gene expression in mice lacking the transcription
      factor NF-E2.
AB  - Previous studies in transgenic mice and cultured cells have indicated that the
      major enhancer function for erythroid cell expression of the globin genes is
      provided by the heterodimeric basic-leucine zipper transcription factor NF-E2.
      Globin gene expression within cultured mouse erythroleukemia cells is highly
      dependent on NF-E2. To examine the requirement for this factor in vivo, we used
      homologous recombination in embryonic stem cells to generate mice lacking the
      hematopoietic-specific subunit, p45 NF-E2. The most dramatic aspect of the
      homozygous mutant mice was an absence of circulating platelets, which led to the
      death of most animals due to hemorrhage. In contrast, the effect of loss of NF-E2
      on the erythroid lineage was surprisingly mild. Although neonates exhibited
      severe anemia and dysmorphic red-cell changes, probably compounded by concomitant
      bleeding, surviving adults exhibited only mild changes consistent with a small
      decrease in the hemoglobin content per cell. p45 NF-E2-null mice responded to
      anemia with compensatory reticulocytosis and splenomegaly. Globin chain synthesis
      was balanced, and switching from fetal to adult globins progressed normally.
      Although these findings are consistent with the substitution of NF-E2 function in
      vivo by one or more compensating proteins, gel shift assays using nuclear
      extracts from p45 NF-E2-null mice failed to reveal novel complexes formed on an
      NF-E2 binding site. Thus, regulation of globin gene transcription through NF-E2
      binding sites in vivo is more complex than has been previously appreciated.

PMID- 7568000
TI  - Prediction of protein folding class using global description of amino acid
      sequence.
AB  - We present a method for predicting protein folding class based on global protein
      chain description and a voting process. Selection of the best descriptors was
      achieved by a computer-simulated neural network trained on a data base consisting
      of 83 folding classes. Protein-chain descriptors include overall composition,
      transition, and distribution of amino acid attributes, such as relative
      hydrophobicity, predicted secondary structure, and predicted solvent exposure.
      Cross-validation testing was performed on 15 of the largest classes. The test
      shows that proteins were assigned to the correct class (correct positive
      prediction) with an average accuracy of 71.7%, whereas the inverse prediction of
      proteins as not belonging to a particular class (correct negative prediction) was
      90-95% accurate. When tested on 254 structures used in this study, the top two
      predictions contained the correct class in 91% of the cases.

PMID- 7567999
TI  - Human fatty acid synthase: properties and molecular cloning.
AB  - Fatty acid synthase (FAS; EC 2.3.1.85) was purified to near homogeneity from a
      human hepatoma cell line, HepG2. The HepG2 FAS has a specific activity of 600
      nmol of NADPH oxidized per min per mg, which is about half that of chicken liver
      FAS. All the partial activities of human FAS are comparable to those of other
      animal FASs, except for the beta-ketoacyl synthase, whose significantly lower
      activity is attributable to the low 4'-phosphopantetheine content of HepG2 FAS.
      We cloned the human brain FAS cDNA. The cDNA sequence has an open reading frame
      of 7512 bp that encodes 2504 amino acids (M(r), 272,516). The amino acid sequence
      of the human FAS has 79% and 63% identity, respectively, with the sequences of
      the rat and chicken enzymes. Northern analysis revealed that human FAS mRNA was
      about 9.3 kb in size and that its level varied among human tissues, with brain,
      lung, and liver tissues showing prominent expression. The nucleotide sequence of
      a segment of the HepG2 FAS cDNA (bases 2327-3964) was identical to that of the
      cDNA from normal human liver and brain tissues, except for a 53-bp sequence
      (bases 3892-3944) that does not alter the reading frame. This altered sequence is
      also present in HepG2 genomic DNA. The origin and significance of this sequence
      variance in the HepG2 FAS gene are unclear, but the variance apparently does not
      contribute to the lower activity of HepG2 FAS.

PMID- 7568002
TI  - Identification and localization of huntingtin in brain and human lymphoblastoid
      cell lines with anti-fusion protein antibodies.
AB  - The Huntington disease (HD) phenotype is associated with expansion of a
      trinucleotide repeat in the IT15 gene, which is predicted to encode a 348-kDa
      protein named huntington. We used polyclonal and monoclonal anti-fusion protein
      antibodies to identify native huntingtin in rat, monkey, and human. Western blots
      revealed a protein with the expected molecular weight which is present in the
      soluble fraction of rat and monkey brain tissues and lymphoblastoid cells from
      control cases. In lymphoblastoid cell lines from juvenile-onset heterozygote HD
      cases, both normal and mutant huntingtin are expressed, and increasing repeat
      expansion leads to lower levels of the mutant protein. Immunocytochemistry
      indicates that huntingtin is located in neurons throughout the brain, with the
      highest levels evident in larger neurons. In the human striatum, huntingtin is
      enriched in a patch-like distribution, potentially corresponding to the first
      areas affected in HD. Subcellular localization of huntingtin is consistent with a
      cytosolic protein primarily found in somatodendritic regions. Huntingtin appears
      to particularly associate with microtubules, although some is also associated
      with synaptic vesicles. On the basis of the localization of huntingtin in
      association with microtubules, we speculate that the mutation impairs the
      cytoskeletal anchoring or transport of mitochondria, vesicles, or other
      organelles or molecules.

PMID- 7568001
TI  - Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by
      interleukins 2 and 15.
AB  - The cytokines interleukin 2 (IL-2) and IL-15 have similar biological effects on T
      cells and bind common hematopoietin receptor subunits. Pathways that involve
      Janus kinases (JAKs) and signal transducers and activators of transcription
      (STATs) have been shown to be important for hematopoietin receptor signaling. In
      this study we identify the STAT proteins activated by IL-2 and IL-15 in human T
      cells. IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and
      STAT5, and DNA-binding complexes containing STAT3 and STAT5 were rapidly
      activated by these cytokines in T cells. IL-4 induced tyrosine phosphorylation
      and activation of STAT3 but not STAT5. JAK1 and JAK3 were tyrosine-phosphorylated
      in response to IL-2 and IL-15. Hence, the JAK and STAT molecules that are
      activated in response to IL-2 and IL-15 are similar but differ from those induced
      by IL-4. These observations identify the STAT proteins activated by IL-2 and IL
      15 and therefore define signaling pathways by which these T-cell growth factors
      may regulate gene transcription.

PMID- 7568003
TI  - High frequency of sex and equal frequencies of mating types in natural
      populations of the ciliate Tetrahymena thermophila.
AB  - In ciliate protists, sex involves the temporary joining of two cells of
      compatible mating type, followed by meiosis and exchange of gametic nuclei
      between conjugants. Reproduction is by asexual binary fission following
      conjugation. For the many ciliates with fixed multiple mating types, frequency
      dependent sex-ratio theory predicts equal frequencies of mating types, if sex is
      common in nature. Here, we report that in natural populations of Tetrahymena
      thermophila sexually immature cells, indicative of recent conjugation, are found
      from spring through fall. In addition, the seven mating types occur in
      approximately equal frequencies, and these frequencies appear to be maintained by
      interaction between complex, multiple mat alleles and environmental conditions
      during conjugation. Such genotype-environment interaction determining mating type
      frequency is rare among ciliates.

PMID- 7568004
TI  - Ligand-induced endocytosis of epidermal growth factor receptors that are
      defective in binding adaptor proteins.
AB  - Ligand-activated epidermal growth factor receptors (EGFRs) associate with coated
      pit adaptor proteins (AP2) in vivo, implying a mechanism for receptor retention
      in coated pits during internalization. Using an in vitro binding assay, we
      localized the adaptor binding determinant to residues 970-991 of EGFRs and
      confirmed specificity by competition with a synthetic peptide corresponding to
      this sequence. A mutant EGFR lacking this AP2 binding determinant did not
      associate with AP2 in vivo but demonstrated internalization and down-regulation
      kinetics indistinguishable from its wild-type counterpart. Immunocytochemistry
      confirmed ligand-induced internalization of the mutant EGFR. These data suggest
      that endocytic determinants are distinct from AP2 binding determinants and that
      processes other than association with AP2 regulate endocytosis of EGFRs.

PMID- 7568005
TI  - Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in
      the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.
AB  - The interleukin 2 receptor (IL-2R) consists of three subunits, the IL-2R alpha,
      IL-2R beta c, and IL-2R gamma c chains. Two Janus family protein tyrosine kinases
      (PTKs), Jak1 and Jak3, were shown to associate with IL-2R beta c and IL-2R gamma
      c, respectively, and their PTK activities are increased after IL-2 stimulation. A
      Jak3 mutant with truncation of the C-terminal PTK domain lacks its intrinsic
      kinase activity but can still associate with IL-2R gamma c. In a hematopoietic
      cell line, F7, that responds to either IL-2 or IL-3, overexpression of this Jak3
      mutant results in selective inhibition of the IL-2-induced activation of
      Jak1/Jak3 PTKs and of cell proliferation. Of the three target nuclear
      protooncogenes of the IL-2 signaling, c-fos and c-myc genes, but not the bcl-2
      gene, were found to be impaired. On the other hand, overexpression of the
      dominant negative form of the IL-2R gamma c chain, which lacks most of its
      cytoplasmic domain, in F7 cells resulted in the inhibition of all three
      protooncogenes. These results provide a further molecular basis for the critical
      role of Jak3 in IL-2 signaling and also suggest a Jak PTK-independent signaling
      pathway(s) for the bcl-2 gene induction by IL-2R.

PMID- 7568007
TI  - Molecular characterization of a second melatonin receptor expressed in human
      retina and brain: the Mel1b melatonin receptor.
AB  - A G protein-coupled receptor for the pineal hormone melatonin was recently cloned
      from mammals and designated the Mel1a melatonin receptor. We now report the
      cloning of a second G protein-coupled melatonin receptor from humans and
      designate it the Mel1b melatonin receptor. The Mel1b receptor cDNA encodes a
      protein of 362 amino acids that is 60% identical at the amino acid level to the
      human Mel1a receptor. Transient expression of the Mel1b receptor in COS-1 cells
      results in high-affinity 2-[125I]iodomelatonin binding (Kd = 160 +/- 30 pM). In
      addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding
      by eight ligands is similar to that exhibited by the Mel1a melatonin receptor.
      Functional studies of NIH 3T3 cells stably expressing the Mel1b melatonin
      receptor indicate that it is coupled to inhibition of adenylyl cyclase.
      Comparative reverse transcription PCR shows that the Mel1b melatonin receptor is
      expressed in retina and, to a lesser extent, brain. PCR analysis of human-rodent
      somatic cell hybrids maps the Mel1b receptor gene (MTNR1B) to human chromosome
      11q21-22. The Mel1b melatonin receptor may mediate the reported actions of
      melatonin in retina and participate in some of the neurobiological effects of
      melatonin in mammals.

PMID- 7568006
TI  - Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles
      for cytokines RANTES and MCP-1.
AB  - Chronic rejection, the most important cause of long-term graft failure, is
      thought to result from both alloantigen-dependent and -independent factors. To
      examine these influences, cytokine dynamics were assessed by semiquantitative
      competitive reverse transcriptase-PCR and by immunohistology in an established
      rat model of chronic rejection lf renal allografts. Isograft controls develop
      morphologic and immunohistologic changes that are similar to renal allograft
      changes, although quantitatively less intense and at a delayed speed; these are
      thought to occur secondary to antigen-independent events. Sequential cytokine
      expression was determined throughout the process. During an early reversible
      allograft rejection episode, both T-cell associated [interleukin (IL) 2, IL-2
      receptor, IL-4, and interferon gamma] and macrophage (IL-1 alpha, tumor necrosis
      factor alpha, and IL-6) products were up-regulated despite transient
      immunosuppression. RANTES (regulated upon activation, normal T-cell expressed and
      secreted) peaked at 2 weeks; intercellular adhesion molecule (ICAM-1) was
      maximally expressed at 6 weeks. Macrophage products such as monocyte
      chemoattractant protein (MCP-1) increased dramatically (to 10 times), presaging
      intense peak macrophage infiltration at 16 weeks. In contrast, in isografts, ICAM
      1 peaked at 24 weeks. MCP-1 was maximally expressed at 52 weeks, commensurate
      with a progressive increase in infiltrating macrophages. Cytokine expression in
      the spleen of allograft and isograft recipients was insignificant. We conclude
      that chronic rejection of kidney allografts in rats is predominantly a local
      macrophage-dependent event with intense up-regulation of macrophage products such
      as MCP-1, IL-6, and inducible nitric oxide synthase. The cytokine expression in
      isografts emphasizes the contribution of antigen-independent events. The dynamics
      of RANTES expression between early and late phases of chronic rejection suggest a
      key role in mediating the events of the chronic process.

PMID- 7568009
TI  - Mathematical analysis of activation thresholds in enzyme-catalyzed positive
      feedbacks: application to the feedbacks of blood coagulation.
AB  - A hierarchy of enzyme-catalyzed positive feedback loops is examined by
      mathematical and numerical analysis. Four systems are described, from the
      simplest, in which an enzyme catalyzes its own formation from an inactive
      precursor, to the most complex, in which two sequential feedback loops act in a
      cascade. In the latter we also examine the function of a long-range feedback, in
      which the final enzyme produced in the second loop activates the initial step in
      the first loop. When the enzymes generated are subject to inhibition or
      inactivation, all four systems exhibit threshold properties akin to excitable
      systems like neuron firing. For those that are amenable to mathematical analysis,
      expressions are derived that relate the excitation threshold to the kinetics of
      enzyme generation and inhibition and the initial conditions. For the most complex
      system, it was expedient to employ numerical simulation to demonstrate threshold
      behavior, and in this case long-range feedback was seen to have two distinct
      effects. At sufficiently high catalytic rates, this feedback is capable of
      exciting an otherwise subthreshold system. At lower catalytic rates, where the
      long-range feedback does not significantly affect the threshold, it nonetheless
      has a major effect in potentiating the response above the threshold. In
      particular, oscillatory behavior observed in simulations of sequential feedback
      loops is abolished when a long-range feedback is present.

PMID- 7568008
TI  - A trace component of ginseng that inhibits Ca2+ channels through a pertussis
      toxin-sensitive G protein.
AB  - A crude extract from ginseng root inhibits high-threshold, voltage-dependent Ca2+
      channels through an unknown receptor linked to a pertussis toxin-sensitive G
      protein. We now have found the particular compound that seems responsible for the
      effect: it is a saponin, called ginsenoside Rf (Rf), that is present in only
      trace amounts within ginseng. At saturating concentrations, Rf rapidly and
      reversibly inhibits N-type, and other high-threshold, Ca2+ channels in rat
      sensory neurons to the same degree as a maximal dose of opioids. The effect is
      dose-dependent (half-maximal inhibition: 40 microM) and it is virtually
      eliminated by pretreatment of the neurons with pertussis toxin, an inhibitor of
      G(o) and Gi GTP-binding proteins. Other ginseng saponins--ginsenosides Rb1, Rc,
      Re, and Rg1--caused relatively little inhibition of Ca2+ channels, and lipophilic
      components of ginseng root had no effect. Antagonists of a variety of
      neurotransmitter receptors that inhibit Ca2+ channels fail to alter the effect of
      Rf, raising the possibility that Rf acts through another G protein-linked
      receptor. Rf also inhibits Ca2+ channels in the hybrid F-11 cell line, which
      might, therefore, be useful for molecular characterization of the putative
      receptor for Rf. Because it is not a peptide and it shares important cellular and
      molecular targets with opioids, Rf might be useful in itself or as a template for
      designing additional modulators of neuronal Ca2+ channels.

PMID- 7568010
TI  - Rat skeletal muscle selenoprotein W: cDNA clone and mRNA modulation by dietary
      selenium.
AB  - Rat skeletal muscle selenoprotein W cDNA was isolated and sequenced. The
      isolation strategy involved design of degenerate PCR primers from reverse
      translation of a partial peptide sequence. A reverse transcription-coupled PCR
      product from rat muscle mRNA was used to screen a muscle cDNA library prepared
      from selenium-supplemented rats. The cDNA sequence confirmed the known protein
      primary sequence, including a selenocysteine residue encoded by TGA, and
      identified residues needed to complete the protein sequence. RNA folding
      algorithms predict a stem-loop structure in the 3' untranslated region of the
      selenoprotein W mRNA that resembles selenocysteine insertion sequence (SE-CIS)
      elements identified in other selenocysteine coding cDNAs. Dietary regulation of
      selenoprotein W mRNA was examined in rat muscle. Dietary selenium at 0.1 ppm as
      selenite increased muscle mRNA 4-fold relative to a selenium-deficient diet.
      Higher dietary selenium produced no further increase in mRNA levels.

PMID- 7568014
TI  - The urease locus of Mycobacterium tuberculosis and its utilization for the
      demonstration of allelic exchange in Mycobacterium bovis bacillus Calmette
      Guerin.
AB  - The ureABC genes of Mycobacterium tuberculosis were cloned. By using a set of
      degenerate primers corresponding to a conserved region of the urease enzyme (EC
      3.5.1.5), a fragment of the expected size was amplified by PCR and was used to
      screen a M. tuberculosis cosmid library. Three open reading frames with extensive
      similarity to the urease genes from other organisms were found. The locus was
      mapped on the chromosome, using an ordered M. tuberculosis cosmid library. A
      suicide vector containing a ureC gene disrupted by a kanamycin marker (aph) was
      used to construct a urease-negative Mycobacterium bovis bacillus Calmette-Guerin
      mutant by allelic exchange involving replacement of the ureC gene with the
      aph::ureC construct. To our knowledge, allelic exchange has not been reported
      previously in the slow-growing mycobacteria. Homologous recombination will be an
      invaluable genetic tool for deciphering the mechanisms of tuberculosis
      pathogenesis, a disease that causes 3 x 10(6) deaths a year worldwide.

PMID- 7568013
TI  - Mouse Col18a1 is expressed in a tissue-specific manner as three alternative
      variants and is localized in basement membrane zones.
AB  - We have isolated overlapping cDNAs encoding the N-terminal non-triple-helical
      region of mouse alpha 1(XVIII) collagen and shown that three different variants
      of alpha 1(XVIII) collagen exist. Each of the three variants shows characteristic
      tissue-specific expression patterns. Immunohistochemical studies show positive
      staining for alpha 1(XVIII) collagen along the basement membrane zones of vessels
      in the intestinal villi, the choroid plexus, skin, liver, and kidney. Thus, we
      conclude that alpha 1(XVIII) collagen may interact (directly or indirectly) with
      components in basement membrane zones or on the basal surface of
      endothelial/epithelial cells.

PMID- 7568012
TI  - Formate is the hydrogen donor for the anaerobic ribonucleotide reductase from
      Escherichia coli.
AB  - During anaerobic growth Escherichia coli uses a specific ribonucleoside
      triphosphate reductase (class III enzyme) for the production of
      deoxyribonucleoside triphosphates. In its active form, the enzyme contains an
      iron-sulfur center and an oxygen-sensitive glycyl radical (Gly-681). The radical
      is generated in the inactive protein from S-adenosylmethionine by an auxiliary
      enzyme system present in E. coli. By modification of the previous purification
      procedure, we now prepared a glycyl radical-containing reductase, active in the
      absence of the auxiliary reducing enzyme system. This reductase uses formate as
      hydrogen donor in the reaction. During catalysis, formate is stoichiometrically
      oxidized to CO2, and isotope from [3H]formate appears in water. Thus E. coli uses
      completely different hydrogen donors for the reduction of ribonucleotides during
      anaerobic and aerobic growth. The aerobic class I reductase employs redox-active
      thiols from thioredoxin or glutaredoxin to this purpose. The present results
      strengthen speculations that class III enzymes arose early during the evolution
      of DNA.

PMID- 7568015
TI  - The vesicular monoamine transporter 2 is present in small synaptic vesicles and
      preferentially localizes to large dense core vesicles in rat solitary tract
      nuclei.
AB  - In central neurons, monamine neurotransmitters are taken up and stored within two
      distinct classes of regulated secretory vesicles: small synaptic vesicles and
      large dense core vesicles (DCVs). Biochemical and pharmacological evidence has
      shown that this uptake is mediated by specific vesicular monamine transporters
      (VMATs). Recent molecular cloning techniques have identified the vesicular
      monoamine transporter (VMAT2) that is expressed in brain. This transporter
      determines the sites of intracellular storage of monoamines and has been
      implicated in both the modulation of normal monoaminergic neurotransmission and
      the pathogenesis of related neuropsychiatric disease. We used an antiserum
      against VMAT2 to examine its ultrastructural distribution in rat solitary tract
      nuclei, a region that contains a dense and heterogeneous population of
      monoaminergic neurons. We find that both immunoperoxidase and immunogold labeling
      for VMAT2 localize to DCVs and small synaptic vesicles in axon terminals, the
      trans-Golgi network of neuronal perikarya, tubulovesicles of smooth endoplasmic
      reticulum, and potential sites of vesicular membrane recycling. In axon
      terminals, immunogold labeling for VMAT2 was preferentially associated with DCVs
      at sites distant from typical synaptic junctions. The results provide direct
      evidence that a single VMAT is expressed in two morphologically distinct types of
      regulated secretory vesicles in central monoaminergic neurons.

PMID- 7568017
TI  - Subacute neuropathological effects of microplanar beams of x-rays from a
      synchrotron wiggler.
AB  - Microplanar beam radiation therapy has been proposed to treat brain tumors by
      using a series of rapid exposures to an array of parallel x-ray beams, each beam
      having uniform microscopic thickness and macroscopic breadth (i.e., microplanar).
      Thirty-six rats were exposed head-on either to an upright 4-mm-high, 20- or 37
      microns-wide beam or to a horizontal 7-mm-wide, 42-microns-high beam of mostly 32
      to 126-keV, minimally divergent x-rays from the X17 wiggler at the National
      Synchrotron Light Source at Brookhaven National Laboratory. Parallel slices of
      the head, separated at either 75 or 200 microns on center, were exposed
      sequentially at 310-650 grays (Gy) per second until each skin-entrance absorbed
      dose reached 312, 625, 1250, 2500, 5000, or 10,000 Gy. The rats were euthanized 2
      weeks or 1 month later. Two rats with 10,000-Gy-entrance slices developed brain
      tissue necrosis. All the other 10,000- and 5000-Gy-entrance slices and some of
      the 2500- and 1250-Gy-entrance slices showed loss of neuronal and astrocytic
      nuclei and their perikarya. No other kind of brain damage was evident
      histologically in any rat with entrance absorbed doses < or = 5000 Gy. Brain
      tissues in and between all the 312- and 625-Gy-entrance slices appeared normal.
      This unusual resistance to necrosis is central to the rationale of microplanar
      beam radiation therapy for brain tumors.

PMID- 7568011
TI  - Suppression of lung metastasis of B16 mouse melanoma by N
      acetylglucosaminyltransferase III gene transfection.
AB  - The beta 1-6 structure of N-linked oligosaccharides, formed by beta-1,6-N
      acetylglucosaminyltransferase (GnT-V), is associated with metastatic potential.
      We established a highly metastatic subclone, B16-hm, from low metastatic B16-F1
      murine melanoma cells. The gene encoding beta-1,4-N-acetylglucosaminyltransferase
      (GnT-III) was introduced into the B16-hm cells, and three clones that stably
      expressed high GnT-III activity were obtained. In these transfectants, the
      affinity to leukoagglutinating phytohemagglutinin was reduced, whereas the
      binding to erythroagglutinating phytohemagglutinin was increased, indicating that
      the level of beta 1-6 structure was decreased due to competition for substrate
      between intrinsic GnT-V and ectopically expressed GnT-III. Lung metastasis after
      intravenous injection of the transfectants into syngeneic and nude mice was
      significantly suppressed, suggesting that the decrease in beta 1-6 structure
      suppressed metastasis via a mechanism independent of the murine system. These
      transfectants also displayed decreased invasiveness into Matrigel and inhibited
      cell attachment to collagen and laminin. Cell growth was not affected. Our
      results demonstrate a causative role for beta 1-6 branches in invasion and cell
      attachment in the extravasation stage of metastasis.

PMID- 7568016
TI  - Dissection of a quantitative trait locus for genetic hypertension on rat
      chromosome 10.
AB  - We have previously identified a locus on rat chromosome 10 as carrying a major
      hypertension gene, BP/SP-1. The 100:1 odds support interval for this gene
      extended over a 35-centimorgan (cM) region of the chromosome that included the
      angiotensin I-converting enzyme (ACE) locus as demonstrated in a cross between
      the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive
      Wistar-Kyoto (WKY-0HD) rat. Here we report on the further characterization of
      BP/SP-1, using a congenic strain, WKY-1HD. WKY-1HD animals carry a 6-cM
      chromosomal fragment genotypically identical with SHRSPHD on chromosome 10, 26 cM
      away from the ACE locus. Higher blood pressures in the WKY-1HD strain compared
      with the WKY-0HD strain, as well as absence of linkage of the chromosome 10
      region to blood pressure in an F2 (WKY-1HD x SHRSPHD) population suggested the
      existence of a quantitative trait locus, termed BP/SP-1a, that lies within the
      SHRSP-congenic region in WKY-1HD. Linkage analysis in the F2 (WKY-0HD x SHRSPHD)
      cross revealed that BP/SP-1a is linked to basal blood pressure, whereas a second
      locus on chromosome 10, termed BP/SP-1b, that maps closer to the ACE locus
      cosegregates predominantly with blood pressure after exposure to excess dietary
      NaCl. Thus, we hypothesize that the previously reported effect of BP/SP-1
      represents a composite phenotype that can be dissected into at least two specific
      components on the basis of linkage data and congenic experimentation. One of the
      loci identified, BP/SP-1a, represents the most precisely mapped locus affecting
      blood pressure that has so far been characterized by random-marker genome
      screening.

PMID- 7568020
TI  - On constructing folding heteropolymers.
AB  - Simplified models of the protein-folding process have led to valuable insights
      into the generic properties of the folding of heteropolymers. On the basis of
      theoretical arguments, Shakhnovich and Gutin [(1993) Proc. Natl. Acad. Sci. USA
      90, 7195-7199] have proposed a specific method to generate folding sequences for
      one of these. Here we present a model of folding in heteropolymers that is
      comparable in simplicity but different in spirit to the one studied by
      Shakhnovich and Gutin. In our model, the proposed recipe for constructing folding
      sequence fails. We find that, as a rule, the construction of folding sequences is
      impossible to achieve by looking at the native conformation only. Rather,
      competing conformations have to be taken into account too. An evolutionary
      algorithm that generates folding sequences by optimizing both stability of the
      native state and folding time is described. Remarkably, this algorithm produces,
      among others, sequences that fold reproducibly to metastable states.

PMID- 7568019
TI  - Transcription termination at intrinsic terminators: the role of the RNA hairpin.
AB  - Intrinsic termination of transcription in Escherichia coli involves the formation
      of an RNA hairpin in the nascent RNA. This hairpin plays a central role in the
      release of the transcript and polymerase at intrinsic termination sites on the
      DNA template. We have created variants of the lambda tR2 terminator hairpin and
      examined the relationship between the structure and stability of this hairpin and
      the template positions and efficiencies of termination. The results were used to
      test the simple nucleic acid destabilization model of Yager and von Hippel and
      showed that this model must be modified to provide a distinct role for the rU
      rich sequence in the nascent RNA, since a perfect palindromic sequence that is
      sufficiently long to form an RNA hairpin that could destabilize the entire
      putative 12-bp RNA-DNA hybrid does not trigger termination at the expected
      positions. Rather, our results show that both a stable terminator hairpin and the
      run of 6-8 rU residues that immediately follows are required for effective
      intrinsic termination and that termination occurs at specific and invariant
      template positions relative to these two components. Possible structural or
      kinetic modifications of the simple model are proposed in the light of these
      findings and of recent results implicating "inchworming" and possible
      conformational heterogeneity of transcription complexes in intrinsic termination.
      Thus, these findings argue that the structure and dimensions of the hairpin are
      important determinants of the termination-elongation decision and suggest that a
      complete mechanism is likely to involve specific interactions of the polymerase,
      the RNA terminator hairpin, and, perhaps, the dT-rich template sequence that
      codes for the run of rU residues at the 3' end of the nascent transcript.

PMID- 7568018
TI  - Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression
      in the locus coeruleus.
AB  - The mechanisms by which stress and anti-depressants exert opposite effects on the
      course of clinical depression are not known. However, potential candidates might
      include neurotrophic factors that regulate the development, plasticity, and
      survival of neurons. To explore this hypothesis, we examined the effects of
      stress and antidepressants on neurotrophin expression in the locus coeruleus
      (LC), which modulates many of the behavioral and physiological responses to
      stress and has been implicated in mood disorders. Using in situ hybridization, we
      demonstrate that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of
      the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA
      levels in the LC. In contrast, chronic treatment with antidepressants decreased
      NT-3 mRNA levels. The effect occurred in response to antidepressants that blocked
      norepinephrine uptake, whereas serotonin-specific reuptake inhibitors did not
      alter NT-3 levels. Electroconvulsive seizures also decreased NT-3 expression in
      the LC as well as the hippocampus. Ntrk3 (neurotrophic tyrosine kinase receptor
      type 3; formerly TrkC), the receptor for NT-3, is expressed in the LC, but its
      mRNA levels did not change with stress or antidepressant treatments. Because, NT
      3 is known to be trophic for LC neurons, our results raise the possibility that
      some of the effects of stress and antidepressants on LC function and plasticity
      could be mediated through NT-3. Moreover, the coexpression of NT-3 and its
      receptor in the LC suggests the potential for autocrine mechanisms of action.

PMID- 7568023
TI  - Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the
      attachment of F-actin to the membrane adhesion complex.
AB  - Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E
      cadherin, guides the establishment of classical epithelial cell polarity and
      contributes to the control of migration, growth, and differentiation. These
      actions involve additional proteins, including alpha- and beta-catenin (or
      plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton. The
      molecular basis for these interactions and their hierarchy of interaction remain
      controversial. We demonstrate a direct interaction between F-actin and alpha (E)
      catenin, an activity not shared by either the cytoplasmic domain of E-cadherin or
      beta-catenin. Sedimentation assays and direct visualization by transmission
      electron microscopy reveal that alpha 1(E)-catenin binds and bundles F-actin in
      vitro with micromolar affinity at a catenin/G-actin monomer ratio of
      approximately 1:7 (mol/mol). Recombinant human beta-catenin can simultaneously
      bind to the alpha-catenin/actin complex but does not bind actin directly.
      Recombinant fragments encompassing the amino-terminal 228 residues of alpha 1(E)
      catenin or the carboxyl-terminal 447 residues individually bind actin in
      cosedimentation assays with reduced affinity compared with the full-length
      protein, and neither fragment bundles actin. Except for similarities to vinculin,
      neither region contains sequences homologous to established actin-binding
      proteins. Collectively these data indicate that alpha 1 (E)-catenin is a novel
      actin-binding and -bundling protein and support a model in which alpha 1(E)
      catenin is responsible for organizing and tethering actin filaments at the zones
      of E-cadherin-mediated cell-cell contact.

PMID- 7568021
TI  - HLA-Cw allele analysis by PCR-restriction fragment length polymorphism: study of
      known and additional alleles.
AB  - We describe a technique for HLA-Cw genotyping by digestion of PCR-amplified genes
      with restriction endonucleases. Locus-specific primers selectively amplified HLA
      Cw sequences from exon 2 in a single PCR that avoided coamplification of other
      classical and nonclassical class I genes. Amplified DNAs were digested with
      selected enzymes. Sixty-three homozygous cell lines from International
      Histocompatibility Workshop X and 113 unrelated individual cells were genotypes
      for HLA-Cw and compared with serology. The present protocol can distinguish 23
      alleles corresponding to the known HLA-Cw sequences. Genotyping of serologically
      undetectable alleles (HLA-Cw Blank) and of heterozygous cells was made possible
      by using this method. Six additional HLA-Cw alleles were identified by unusual
      restriction patterns and confirmed by sequencing; this observation suggests the
      presence of another family of allele-sharing clusters in the HLA-B locus. This
      PCR-restriction endonuclease method provides a simple and convenient approach for
      HLA-Cw DNA typing, allowing the definition of serologically undetectable alleles,
      and will contribute to the evaluation of the biological role of the HLA-C locus.

PMID- 7568022
TI  - Phorbol ester treatment inhibits phosphatidylinositol 3-kinase activation by, and
      association with, CD28, a T-lymphocyte surface receptor.
AB  - CD28 is a costimulatory receptor found on the surface of most T lymphocytes.
      Engagement of CD28 induces interleukin 2 (IL-2) production and cell proliferation
      when combined with an additional signal such as treatment with phorbol ester, an
      activator of protein kinase C. Recent studies have established that after CD28
      ligation, the cytoplasmic domain of CD28 can bind to the 85-kDa subunit of
      phosphatidylinositol 3-kinase (PI3 kinase). There is a concomitant increase in
      PI3 lipid kinase activity that may be important in CD28 signaling. Despite the
      requirement of phorbol 12-myristate 13-acetate (PMA) for effector function, we
      have found, however, that treatment of Jurkat T cells with the phorbol ester PMA
      dramatically inhibits (i) the association of PI3 kinase with CD28, (ii) the
      ability of p85 PI3 kinase to be immunoprecipitated by anti-phosphotyrosine
      antibodies, and (iii) the induction of PI3 kinase activity after stimulation of
      the cells with the anti-CD28 monoclonal antibody 9.3. These changes occur within
      minutes of PMA treatment and are persistent. In addition, we have found that
      wortmannin, a potent inhibitor of PI3 kinase, does not interfere with the
      induction of IL-2 after stimulation of Jurkat T cells with anti-CD28 monoclonal
      antibody and PMA. We conclude that PI3 kinase activity may not be required for
      CD28-dependent IL-2 production from Jurkat T cells in the presence of PMA.

PMID- 7568024
TI  - Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti
      HIV plant proteins MAP30 and GAP31.
AB  - MAP30 (Momordica anti-HIV protein of 30 kDa) and GAP31 (Gelonium anti-HIV protein
      of 31 kDa) are anti-HIV plant proteins that we have identified, purified, and
      cloned from the medicinal plants Momordica charantia and Gelonium multiflorum.
      These antiviral agents are capable of inhibiting infection of HIV type 1 (HIV-1)
      in T lymphocytes and monocytes as well as replication of the virus in already
      infected cells. They are not toxic to normal uninfected cells because they are
      unable to enter healthy cells. MAP30 and GAP31 also possess an N-glycosidase
      activity on 28S ribosomal RNA and a topological activity on plasmid and viral
      DNAs including HIV-1 long terminal repeats (LTRs). LTRs are essential sites for
      integration of viral DNA into the host genome by viral integrase. We therefore
      investigated the effect of MAP30 and GAP31 on HIV-1 integrase. We report that
      both of these antiviral agents exhibit dose-dependent inhibition of HIV-1
      integrase. Inhibition was observed in all of the three specific reactions
      catalyzed by the integrase, namely, 3' processing (specific cleavage of the
      dinucleotide GT from the viral substrate), strand transfer (integration), and
      "disintegration" (the reversal of strand transfer). Inhibition was studied by
      using oligonucleotide substrates with sequences corresponding to the U3 and U5
      regions of HIV LTR. In the presence of 20 ng of viral substrate, 50 ng of target
      substrate, and 4 microM integrase, total inhibition was achieved at equimolar
      concentrations of the integrase and the antiviral proteins, with EC50 values of
      about 1 microM. Integration of viral DNA into the host chromosome is a vital step
      in the replicative cycle of retroviruses, including the AIDS virus. The
      inhibition of HIV-1 integrase by MAP30 and GAP31 suggests that impediment of
      viral DNA integration may play a key role in the anti-HIV activity of these plant
      proteins.

PMID- 7568025
TI  - Mutant rat phosphatidylinositol/phosphatidylcholine transfer proteins
      specifically defective in phosphatidylinositol transfer: implications for the
      regulation of phospholipid transfer activity.
AB  - The mammalian phosphatidylinositol/phosphatidylcholine transfer proteins (PI-TPs)
      catalyze exchange of phosphatidylinositol (PI) or phosphatidylcholine (PC)
      between membrane bilayers in vitro. We find that Ser-25, Thr-59, Pro-78, and Glu
      248 make up a set of rat (r) PI-TP residues, substitution of which effected a
      dramatic reduction in the relative specific activity for PI transfer activity
      without significant effect on PC transfer activity. Thr-59 was of particular
      interest as it is a conserved residue in a highly conserved consensus protein
      kinase C phosphorylation motif in metazoan PI-TPs. Replacement of Thr-59 with
      Ser, Gln, Val, Ile, Asn, Asp, or Glu effectively abolished PI transfer capability
      but was essentially silent with respect to PC transfer activity. These findings
      identify rPI-TP residues that likely cooperate to form a PI head-group
      binding/recognition site or that lie adjacent to such a site. Finally, the
      selective sensitivity of the PI transfer activity of rPI-TP to alteration of Thr
      59 suggests a mechanism for in vivo regulation of rPI-TP activity.

PMID- 7568026
TI  - Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in
      prolactin signal transduction in mouse mammary tissue.
AB  - Prolactin (PRL) induces transcriptional activation of milk protein genes, such as
      the whey acidic protein (WAP), beta-casein, and beta-lactoglobulin genes, through
      a signaling cascade encompassing the Janus kinase Jak2 and the mammary gland
      factor (MGF; also called Stat5), which belongs to the family of proteins of
      signal transducers and activators of transcription (STAT). We isolated and
      sequenced from mouse mammary tissue Stat5 mRNA and a previously unreported
      member, which we named Stat5b (Stat5 is renamed to Stat5a). On the protein level
      Stat5a and Stat5b show a 96% sequence similarity. The 5' and 3' untranslated
      regions of the two mRNAs are not conserved. Stat5a comprises 793 amino acids and
      is encoded by a mRNA of 4.2 kb. The Stat5b mRNA has a size of 5.6 kb and encodes
      a protein of 786 amino acids. Both Stat5a and Stat5b recognized the GAS site
      (gamma-interferon-activating sequence; TTCNNNGAA) in vitro and mediated PRL
      induced transcription in COS cells transfected with a PRL receptor. Stat5b also
      induced basal transcription in the absence of PRL. Similar levels of Stat5a and
      Stat5b mRNAs were found in most tissues of virgin and lactating mice, but a
      differential accumulation of the Stat5 mRNAs was found in muscle and mammary
      tissue. The two RNAs are present in mammary tissue of immature virgin mice, and
      their levels increase up to day 16 of pregnancy, followed by a decline during
      lactation. The increase of Stat5 expression during pregnancy coincides with the
      activation of the WAP gene.

PMID- 7568027
TI  - Restricted and conserved T-cell repertoires involved in allorecognition of class
      II major histocompatibility complex.
AB  - The nature of the alloreactive T-cell response is not yet clearly understood.
      These strong cellular responses are thought to be the basis of allograft
      rejection and graft-vs.-host disease. The question of the extent of responding T
      cell repertoires has so far been addressed by cellular cloning, often combined
      with molecular T-cell receptor (TCR) analysis. Here we present a broad repertoire
      analysis of primed responder cells from mixed lymphocyte cultures in which two
      different DR1/3 responders were stimulated with DR3/4 cells. Repertoire analysis
      was performed by TCR spectratyping, a method by which T cells are analyzed on the
      basis of the complementarity-determining region 3 length of different variable
      region (V) families. Strikingly, both responders showed very similar repertoires
      when the TCR V beta was used as a lineage marker. This was not seen when TCR V
      alpha was analyzed. A different pattern of TCR V beta was observed if the
      stimulating alloantigen was changed. This finding indicates that alloreactive T
      cells form a specific repertoire for each alloantigen. Since conservation appears
      to be linked to TCR V beta, the question of different roles of alpha and beta
      chains in allorecognition is raised.

PMID- 7568028
TI  - Involvement of the double-stranded-RNA-dependent kinase PKR in interferon
      expression and interferon-mediated antiviral activity.
AB  - The signaling mechanisms responsible for the induced expression of interferon
      (IFN) genes by viral infection or double-stranded RNA (dsRNA) are not well
      understood. Here we investigate the role of the interferon-induced dsRNA
      dependent protein kinase PKR in the regulation of IFN induction. Biological
      activities attributed to PKR include regulating protein synthesis, mediating IFN
      actions, and functioning as a possible tumor suppressor. Since binding of dsRNA
      is required for its activation, PKR has been considered as a candidate signal
      transducer for regulating IFN expression. To examine this role of PKR, loss-of
      function phenotypes in stable transformants of promonocytic U-937 cells were
      achieved by two different strategies, overexpression of an antisense PKR
      transcript or a dominant negative PKR mutant gene. Both types of PKR-deficient
      cells were more permissive for viral replication than the control U-937 cells. As
      the result of PKR loss, they also showed impaired induction of IFN-alpha and IFN
      beta genes in response to several inducers--specifically, encephalomyocarditis
      virus, lipopolysaccharide, and phorbol 12-myristate 13-acetate. Interestingly,
      while IFN-alpha induction by dsRNA was impaired in PKR-deficient cells, IFN-beta
      induction remained intact. Loss of PKR function also resulted in decreased
      antiviral activity as elicited by IFN-alpha and, to a greater extent, by IFN
      gamma. These results implicate PKR in the regulation of several antiviral
      activities.

PMID- 7568030
TI  - Hippocampal long-term depression and depotentiation are defective in mice
      carrying a targeted disruption of the gene encoding the RI beta subunit of cAMP
      dependent protein kinase.
AB  - The cAMP-dependent protein kinase (PKA) has been shown to play an important role
      in long-term potentiation (LTP) in the hippocampus, but little is known about the
      function of PKA in long-term depression (LTD). We have combined pharmacologic and
      genetic approaches to demonstrate that PKA activity is required for both
      homosynaptic LTD and depotentiation and that a specific neuronal isoform of type
      I regulatory subunit (RI beta) is essential. Mice carrying a null mutation in the
      gene encoding RI beta were established by use of gene targeting in embryonic stem
      cells. Hippocampal slices from mutant mice show a severe deficit in LTD and
      depotentiation at the Schaffer collateral-CA1 synapse. This defect is also
      evident at the lateral perforant path-dentate granule cell synapse in RI beta
      mutant mice. Despite a compensatory increase in the related RI alpha protein and
      a lack of detectable changes in total PKA activity, the hippocampal function in
      these mice is not rescued, suggesting a unique role for RI beta. Since the late
      phase of CA1 LTP also requires PKA but is normal in RI beta mutant mice, our data
      further suggest that different forms of synaptic plasticity are likely to employ
      different combinations of regulatory and catalytic subunits.

PMID- 7568031
TI  - Hippocampal long-term potentiation is impaired in mice lacking brain-derived
      neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor
      (NGF) gene family, has been shown to influence the survival and differentiation
      of specific classes of neurons in vitro and in vivo. The possibility that
      neurotrophins are also involved in processes of neuronal plasticity has only
      recently begun to receive attention. To determine whether BDNF has a function in
      processes such as long-term potentiation (LTP), we produced a strain of mice with
      a deletion in the coding sequence of the BDNF gene. We then used hippocampal
      slices from these mice to investigate whether LTP was affected by this mutation.
      Homo- and heterozygous mutant mice showed significantly reduced LTP in the CA1
      region of the hippocampus. The magnitude of the potentiation, as well as the
      percentage of cases in which LTP could be induced successfully, was clearly
      affected. According to the criteria tested, important pharmacological,
      anatomical, and morphological parameters in the hippocampus of these animals
      appear to be normal. These results suggest that BDNF might have a functional role
      in the expression of LTP in the hippocampus.

PMID- 7568029
TI  - The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein
      involved in cancer chemoprotection and chemotherapy: mechanism of the two
      electron reduction.
AB  - Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2], also
      called DT diaphorase, is a homodimeric FAD-containing enzyme that catalyzes
      obligatory NAD(P)H-dependent two-electron reductions of quinones and protects
      cells against the toxic and neoplastic effects of free radicals and reactive
      oxygen species arising from one-electron reductions. These two-electron
      reductions participate in the reductive bioactivation of cancer chemotherapeutic
      agents such as mitomycin C in tumor cells. Thus, surprisingly, the same enzymatic
      reaction that protects normal cells activates cytotoxic drugs used in cancer
      chemotherapy. The 2.1-A crystal structure of rat liver quinone reductase reveals
      that the folding of a portion of each monomer is similar to that of flavodoxin, a
      bacterial FMN-containing protein. Two additional portions of the polypeptide
      chains are involved in dimerization and in formation of the two identical
      catalytic sites to which both monomers contribute. The crystallographic
      structures of two FAD-containing enzyme complexes (one containing NADP+, the
      other containing duroquinone) suggest that direct hydride transfers from NAD(P)H
      to FAD and from FADH2 to the quinone [which occupies the site vacated by NAD(P)H]
      provide a simple rationale for the obligatory two-electron reductions involving a
      ping-pong mechanism.

PMID- 7568032
TI  - Interaction of an alkylating camptothecin derivative with a DNA base at
      topoisomerase I-DNA cleavage sites.
AB  - DNA topoisomerase I (top1) is a ubiquitous nuclear enzyme. It is specifically
      inhibited by camptothecin, a natural product derived from the bark of the tree
      Camptotheca acuminata. Camptothecin and several of its derivatives are presently
      in clinical trial and exhibit remarkable anticancer activity. The present study
      is a further investigation of the molecular interactions between the drug and the
      enzyme-DNA complex. We utilized an alkylating camptothecin derivative, 7
      chloromethyl-10,11-methylenedioxycamptothecin (7-ClMe-MDO-CPT), and compared its
      activity against calf thymus top1 in a DNA oligonucleotide containing a single
      top1 cleavage site with the activity of its nonalkylating analog, 7-ethyl-10,11
      methylenedioxycamptothecin (7-Et-MDO-CPT). In the presence of top1, 7-ClMe-MDO
      CPT produced a DNA fragment that migrated more slowly than the top1-cleaved DNA
      fragment observed with 7-Et-MDO-CPT. Top1 was unable to religate this fragment in
      the presence of high NaCl concentration or proteinase K at 50 degrees C. This
      fragment was resistant to piperidine treatment and was also formed with an
      oligonucleotide containing a 7-deazaguanine at the 5' terminus of the top1
      cleaved DNA (base + 1). It was however cleaved by formic acid treatment followed
      by piperidine. These observations are consistent with alkylation of the +1 base
      (adenine or guanine) by 7-ClMe-MDO-CPT in the presence of top1 covalent complexes
      and provide direct evidence that camptothecins inhibit top1 by binding at the
      enzyme-DNA interface.

PMID- 7568033
TI  - Phosphorylation-dependent conformational changes in OmpR, an osmoregulatory DNA
      binding protein of Escherichia coli.
AB  - Osmoregulated porin gene expression in Escherichia coli is controlled by the two
      component regulatory system EnvZ and OmpR. EnvZ, the osmosensor, is an inner
      membrane protein and a histidine kinase. EnvZ phosphorylates OmpR, a cytoplasmic
      DNA-binding protein, on an aspartyl residue. Phospho-OmpR binds to the promoters
      of the porin genes to regulate the expression of ompF and ompC. We describe the
      use of limited proteolysis by trypsin and ion spray mass spectrometry to
      characterize phospho-OmpR and the conformational changes that occur upon
      phosphorylation. Our results are consistent with a two-domain structure for OmpR,
      an N-terminal phosphorylation domain joined to a C-terminal DNA-binding domain by
      a flexible linker region. In the presence of acetyl phosphate, OmpR is
      phosphorylated at only one site. Phosphorylation induces a conformational change
      that is transmitted to the C-terminal domain via the central linker. Previous
      genetic analysis identified a region in the C-terminal domain that is required
      for transcriptional activation. Our results indicate that this region is within a
      surface-exposed loop. We propose that this loop contacts the alpha subunit of RNA
      polymerase to activate transcription. Mass spectrometry also reveals an unusual
      dephosphorylated form of OmpR, the potential significance of which is discussed.

PMID- 7568034
TI  - Identification of human cyclin-dependent kinase 8, a putative protein kinase
      partner for cyclin C.
AB  - Metazoan cyclin C was originally isolated by virtue of its ability to rescue
      Saccharomyces cerevisiae cells deficient in G1 cyclin function. This suggested
      that cyclin C might play a role in cell cycle control, but progress toward
      understanding the function of this cyclin has been hampered by the lack of
      information on a potential kinase partner. Here we report the identification of a
      human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to
      be a physiological partner of cyclin C. A specific interaction between K35 and
      cyclin C could be demonstrated after translation of CDKs and cyclins in vitro.
      Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from
      HeLa cells, indicating that the two proteins form a complex also in vivo. The K35
      cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair
      recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae.
      Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated
      with the mammalian transcription apparatus, perhaps involved in relaying growth
      regulatory signals.

PMID- 7568035
TI  - Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in
      global DNA repair but exhibit normal transcription-coupled repair and enhanced UV
      resistance.
AB  - We investigated whether mutations in the p53 tumor suppressor gene alter UV
      sensitivity and/or repair of UV-induced DNA damage in primary human skin
      fibroblasts from patients with Li-Fraumeni syndrome, heterozygous for mutations
      in one allele of the p53 gene (p53 wt/mut) and sublines expressing only mutant
      p53 (p53 mut). The p53 mut cells were more resistant than the p53 wt/mut cells to
      UV cytotoxicity and exhibited less UV-induced apoptosis. DNA repair analysis
      revealed reduced removal of cyclobutane pyrimidine dimers from overall genomic
      DNA in vivo in p53 mut cells compared with p53 wt/mut or normal cells. However,
      p53 mut cells retained the ability to preferentially repair damage in the
      transcribed strands of expressed genes (transcription-coupled repair). These
      results suggest that loss of p53 function may lead to greater genomic instability
      by reducing the efficiency of DNA repair but that cellular resistance to DNA
      damaging agents may be enhanced through elimination of apoptosis.

PMID- 7568036
TI  - Association of mitogen-activated protein kinase with the microtubule
      cytoskeleton.
AB  - Using indirect immunofluorescence microscopy and biochemical techniques, we have
      determined that approximately one-third of the total mitogen-activated protein
      kinase (MAPK) is associated with the microtubule cytoskeleton in NIH 3T3 mouse
      fibroblasts. This population of enzyme can be separated from the soluble form
      that is found distributed throughout the cytosol and is also present in the
      nucleus after mitogen stimulation. The microtubule-associated enzyme pool
      constitutes half of all detectable MAPK activity after mitogenic stimulation.
      These findings extend the known in vivo associations of MAPK with microtubules to
      include the entire microtubule cytoskeleton of proliferating cells, and they
      suggest that a direct association of MAPK with microtubules may be in part
      responsible for the observed correlations between MAPK activities and
      cytoskeletal alteration.

PMID- 7568037
TI  - Identification and characterization of putative transposable DNA elements in
      solanaceous plants and Caenorhabditis elegans.
AB  - Several families of putative transposable elements (TrEs) in both solanaceous
      plants and Caenorhabditis elegans have been identified by screening the DNA data
      base for inverted repeated domains present in multiple copies in the genome. The
      elements are localized within intron and flanking regions of many genes. These
      elements consist of two inverted repeats flanking sequences ranging from 5 bp to
      > 500 bp. Identification of multiple elements in which sequence conservation
      includes both the flanking and internal regions implies that these TrEs are
      capable of duplicative transposition. Two of the elements were identified in
      promoter regions of the tomato (Lycoperiscon esculentum) polygalacturonase and
      potato (Solanum tuberosum) Win1 genes. The element in the polygalacturonase
      promoter spans a known regulatory region. In both cases, ancestral DNA sequences,
      which represent potential recombination target sequences prior to insertion of
      the elements, have been cloned from related species. The sequences of the
      inverted repeated domains in plants and C. elegans show a high degree of
      phylogenetic conservation. While frequency of the different elements is variable,
      some are present in very high copy number. A member of a single C. elegans TrE
      family is observed approximately once every 20 kb in the genome. The abundance of
      the described TrEs suggests utility in the genomic analysis of these and related
      organisms.

PMID- 7568039
TI  - Structure of human T-cell receptors specific for an immunodominant myelin basic
      protein peptide: positioning of T-cell receptors on HLA-DR2/peptide complexes.
AB  - T-cell receptors (TCRs) recognize peptide bound within the relatively conserved
      structural framework of major histocompatibility complex (MHC) class I or class
      II molecules but can discriminate between closely related MHC molecules. The
      structural basis for the specificity of ternary complex formation by the TCR and
      MHC/peptide complexes was examined for myelin basic protein (MBP)-specific T-cell
      clones restricted by different DR2 subtypes. Conserved features of this system
      allowed a model for positioning of the TCR on DR2/peptide complexes to be
      developed: (i) The DR2 subtypes that presented the immunodominant MBP peptide
      differed only at a few polymorphic positions of the DR beta chain. (ii) TCR
      recognition of a polymorphic residue on the helical portion of the DR beta chain
      (position DR beta 67) was important in determining the MHC restriction. (iii) The
      TCR variable region (V) alpha 3.1 gene segment was used by all of the T-cell
      clones. TCR V beta usage was more diverse but correlated with the MHC restriction
      -i.e., with the polymorphic DR beta chains. (iv) Two clones with conserved TCR
      alpha chains but different TCR beta chains had a different MHC restriction but a
      similar peptide specificity. The difference in MHC restriction between these T
      cell clones appeared due to recognition of a cluster of polymorphic DR beta-chain
      residues (DR beta 67-71). MBP-(85-99)-specific TCRs therefore appeared to be
      positioned on the DR2/peptide complex such that the TCR beta chain contacted the
      polymorphic DR beta-chain helix while the conserved TCR alpha chain contacted the
      nonpolymorphic DR alpha chain.

PMID- 7568040
TI  - Modification of rhodamine staining allows identification of hematopoietic stem
      cells with preferential short-term or long-term bone marrow-repopulating ability.
AB  - We have developed a modified rhodamine (Rho) staining procedure to study uptake
      and efflux in murine hematopoietic stem cells. Distinct populations of Rho++
      (bright), Rho+ (dull), and Rho- (negative) cells could be discriminated. Sorted
      Rho- cells were subjected to a second Rho staining procedure with the P
      glycoprotein blocking agent verapamil (VP). Most cells became Rho positive [Rho
      /Rho(VP)+ cells] and some remained Rho negative [Rho-/Rho(VP)- cells]. These cell
      fractions were characterized by their marrow-repopulating ability in a syngeneic,
      sex-mismatch transplantation model. Short-term repopulating ability was
      determined by recipient survival for at least 6 weeks after lethal irradiation
      and transplantation--i.e., radioprotection. Long-term repopulating ability at 6
      months after transplantation was measured by fluorescence in situ hybridization
      with a Y-chromosome-specific probe, by graft function and recipient survival.
      Marrow-repopulating cells were mainly present in the small Rho- cell fraction.
      Transplantation of 30 Rho- cells resulted in 50% radioprotection and > 80% donor
      repopulation in marrow, spleen, and thymus 6 months after transplantation.
      Cotransplantation of cells from both fractions in individual mice directly showed
      that within this Rho- cell fraction, the Rho-/Rho(VP)+ cells exhibited mainly
      short-term and the Rho-/Rho(VP)- cells exhibited mainly long-term repopulating
      ability. Our results indicate that hematopoietic stem cells have relatively high
      P-glycoprotein expression and that the cells responsible for long-term
      repopulating ability can be separated from cells exhibiting short-term
      repopulating ability, probably by a reduced mitochondrial Rho-binding capacity.

PMID- 7568038
TI  - p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth
      factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase
      ITK: implications for T-cell costimulation.
AB  - T-cell activation requires cooperative signals generated by the T-cell antigen
      receptor zeta-chain complex (TCR zeta-CD3) and the costimulatory antigen CD28.
      CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase
      (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT),
      and the complex between growth factor receptor-bound protein 2 and son of
      sevenless guanine nucleotide exchange protein (GRB-2-SOS). PI 3-kinase and GRB-2
      bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of
      intrinsic Src-homology 2 (SH2) domains. The requirement for tyrosine
      phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an
      intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2
      by CD28. Candidate kinases include p56Lck, p59Fyn, zeta-chain-associated 70-kDa
      protein (ZAP-70), and ITK. In this study, we demonstrate in coexpression studies
      that p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn
      Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and
      GRB-2 SH2 binding to CD28. Phosphatase digestion of CD28 eliminated binding. In
      contrast to Src kinases, ZAP-70 and ITK failed to induce these events. Further,
      ITK binding to CD28 was dependent on the presence of p56Lck and is thus likely to
      act downstream of p56Lck/p59Fyn in a signaling cascade. p56Lck is therefore
      likely to be a central switch in T-cell activation, with the dual function of
      regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling.

PMID- 7568041
TI  - Genetic variation in vulnerability to the behavioral effects of neonatal
      hippocampal damage in rats.
AB  - We explored how two independent variables, one genetic (i.e., specific rat
      strains) and another environmental (i.e., a developmental excitotoxic hippocampal
      lesion), contribute to phenotypic variation. Sprague-Dawley (SD), Fischer 344
      (F344), and Lewis rats underwent two grades of neonatal excitotoxic damage: small
      and large ventral hippocampal (SVH and LVH) lesions. Locomotion was tested before
      puberty [postnatal day 35 (P35)] and after puberty (P56) following exposure to a
      novel environment or administration of amphetamine. The behavioral effects were
      strain- and lesion-specific. As shown previously, SD rats with LVH lesions
      displayed enhanced spontaneous and amphetamine-induced locomotion as compared
      with controls at P56, but not at P35. SVH lesions in SD rats had no effect at any
      age. In F344 rats with LVH lesions, enhanced spontaneous and amphetamine-induced
      locomotion appeared early (P35) and was exaggerated at P56. SVH lesions in F344
      rats resulted in a pattern of effects analogous to LVH lesions in SD rats--i.e.,
      postpubertal onset of hyperlocomotion (P56). In Lewis rats, LVH lesions had no
      significant effect on novelty- or amphetamine-induced locomotion at any age.
      These data show that the degree of genetic predisposition and the extent of early
      induced hippocampal defect contribute to the particular pattern of behavioral
      outcome. These results may have implications for modeling interactions of genetic
      and environmental factors involved in schizophrenia, a disorder characterized by
      phenotypic heterogeneity, genetic predisposition, a developmental hippocampal
      abnormality, and vulnerability to environmental stress.

PMID- 7568042
TI  - Expression of a plant viral polycistronic mRNA in yeast, Saccharomyces
      cerevisiae, mediated by a plant virus translational transactivator.
AB  - We demonstrate that the cauliflower mosaic virus (CaMV) gene VI product can
      transactivate the expression of a reporter gene in bakers' yeast, Saccharomyces
      cerevisiae. The gene VI coding sequence was placed under the control of the
      galactose-inducible promoter GAL1, which is presented in the yeast shuttle vector
      pYES2, to create plasmid JS169. We also created a chloramphenicol
      acetyltransferase (CAT) reporter plasmid, JS161, by inserting the CAT reporter
      gene in-frame into CaMV gene II and subsequently cloning the entire CaMV genome
      into the yeast vector pRS314. When JS161 was transformed into yeast and
      subsequently assayed for CAT activity, only a very low level of CAT activity was
      detected in cellular extracts. To investigate whether the CaMV gene VI product
      would mediate an increase in CAT activity, we cotransformed yeast with JS169 and
      JS161. Upon induction with galactose, we found that CAT activity in yeast
      transformed with JS161 and JS169 was about 19 times higher than the level in the
      transformants that contained only JS161. CAT activity was dependent on the
      presence of the gene VI protein, because essentially no CAT activity was detected
      in yeast cells grown in the presence of glucose, which represses expression from
      the GAL1 promoter. RNase protection assays showed that the gene VI product had no
      effect on transcription from the 35S RNA promoter, demonstrating that regulation
      was occurring at the translation level. This yeast system will prove useful for
      understanding how the gene VI product of CaMV mediates the translation of genes
      present on a eukaryotic polycistronic mRNA.

PMID- 7568043
TI  - Crystallographic evidence for the action of potassium, thallium, and lithium ions
      on fructose-1,6-bisphosphatase.
AB  - Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate 1
      phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions to hydrolyze
      alpha-D-fructose 1,6-bisphosphate. Although not required for catalysis,
      monovalent cations modify the enzyme activity; K+ and Tl+ ions are activators,
      whereas Li+ ions are inhibitors. Their mechanisms of action are still unknown. We
      report here crystallographic structures of pig kidney Fru-1,6-Pase complexed with
      K+, Tl+, or both Tl+ and Li+. In the T form Fru-1,6-Pase complexed with the
      substrate analogue 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) and Tl+
      or K+ ions, three Tl+ or K+ binding sites are found. Site 1 is defined by Glu-97,
      Asp-118, Asp-121, Glu-280, and a 1-phosphate oxygen of AhG-1,6-P2; site 2 is
      defined by Glu-97, Glu-98, Asp-118, and Leu-120. Finally, site 3 is defined by
      Arg-276, Glu-280, and the 1-phosphate group of AhG-1,6-P2. The Tl+ or K+ ions at
      sites 1 and 2 are very close to the positions previously identified for the
      divalent metal ions. Site 3 is specific to K+ or Tl+. In the divalent metal ion
      complexes, site 3 is occupied by the guanidinium group of Arg-276. These
      observations suggest that Tl+ or K+ ions can substitute for Arg-276 in the active
      site and polarize the 1-phosphate group, thus facilitating nucleophilic attack on
      the phosphorus center. In the T form complexed with both Tl+ and Li+ ions, Li+
      replaces Tl+ at metal site 1. Inhibition by lithium very likely occurs as it
      binds to this site, thus retarding turnover or phosphate release. The present
      study provides a structural basis for a similar mechanism of inhibition for
      inositol monophosphatase, one of the potential targets of lithium ions in the
      treatment of manic depression.

PMID- 7568045
TI  - Negative activation enthalpies in the kinetics of protein folding.
AB  - Although the rates of chemical reactions become faster with increasing
      temperature, the converse may be observed with protein-folding reactions. The
      rate constant for folding initially increases with temperature, goes through a
      maximum, and then decreases. The activation enthalpy is thus highly temperature
      dependent because of a large change in specific heat (delta Cp). Such a delta Cp
      term is usually presumed to be a consequence of a large decrease in exposure of
      hydrophobic surfaces to water as the reaction proceeds from the denatured state
      to the transition state for folding: the hydrophobic side chains are surrounded
      by "icebergs" of water that melt with increasing temperature, thus making a large
      contribution to the Cp of the denatured state and a smaller one to the more
      compact transition state. The rate could also be affected by temperature-induced
      changes in the conformational population of the ground state: the heat required
      for the progressive melting of residual structure in the denatured state will
      contribute to delta Cp. By examining two proteins with different refolding
      mechanisms, we are able to find both of these two processes; barley chymotrypsin
      inhibitor 2, which refolds from a highly unfolded state, fits well to a
      hydrophobic interaction model with a constant delta Cp of activation, whereas
      barnase, which refolds from a more structured denatured state, deviates from this
      ideal behavior.

PMID- 7568044
TI  - Functional complementation of the ste6 gene of Saccharomyces cerevisiae with the
      pfmdr1 gene of Plasmodium falciparum.
AB  - The pfmdr1 gene has been associated with a drug-resistant phenotype in Plasmodium
      falciparum, and overexpression of pfmdr1 has been associated with mefloquine- and
      halofantrine-resistant parasites, but little is known about the functional role
      of pfmdr1 in this process. Here, we demonstrate that the pfmdr1 gene expressed in
      a heterologous yeast system functions as a transport molecule and complements a
      mutation in ste6, a gene which encodes a mating pheromone a-factor export
      molecule. In addition, the pfmdr1 gene containing two mutations which are
      associated with naturally occurring chloroquine resistance abolishes this mating
      phenotype, suggesting that these genetic polymorphisms alter this transport
      function. Our results support the functional role of pfmdr1 as a transport
      molecule in the mediation of drug resistance and provide an assay system to
      address the nature of this transport function.

PMID- 7568046
TI  - Molecular characterization of PsbW, a nuclear-encoded component of the
      photosystem II reaction center complex in spinach.
AB  - We describe the isolation and characterization of cDNAs encoding the precursor
      polypeptide of the 6.1-kDa polypeptide associated with the reaction center core
      of the photosystem II complex from spinach. PsbW, the gene encoding this
      polypeptide, is present in a single copy per haploid genome. The mature
      polypeptide with 54 amino acid residues is characterized by a hydrophobic
      transmembrane segment, and, although an intrinsic membrane protein, it carries a
      bipartite transit peptide of 83 amino acid residues which directs the N terminus
      of the mature protein into the chloroplast lumen. Thylakoid integration of this
      polypeptide does not require a delta pH across the membrane, nor is it azide
      sensitive, suggesting that the polypeptide chain inserts spontaneously in an as
      yet unknown way. The PsbW mRNA levels are light regulated. Similar to cytochrome
      b559 and PsbS, but different from the chlorophyll-complexing polypeptides D1, D2,
      CP43, and CP47 of photosystem II, PsbW is present in etiolated spinach seedlings.

PMID- 7568047
TI  - Glial cell line-derived neurotrophic factor but not transforming growth factor
      beta 3 prevents delayed degeneration of nigral dopaminergic neurons following
      striatal 6-hydroxydopamine lesion.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor
      beta 3 (TGF-beta 3) are members of the TGF-beta superfamily with high
      neurotrophic activity on cultured nigral dopamine neurons. We investigated the
      effects of intracerebral administration of GDNF and TGF-beta 3 on the delayed
      cell death of the dopamine neurons in the rat substantia nigra following 6
      hydroxydopamine lesions of dopaminergic terminals in the striatum. Fluorescent
      retrograde tracer injections and tyrosine hydroxylase immunocytochemistry
      demonstrated nigral degeneration with an onset 1 week after lesion, leading to
      extensive death of nigral neurons 4 weeks postlesion. Administration of
      recombinant human GDNF for 4 weeks over the substantia nigra at a cumulative dose
      of 140 micrograms, starting on the day of lesion, completely prevented nigral
      cell death and atrophy, while a single injection of 10 micrograms 1 week
      postlesion had a partially protective effect. Continuous administration of TGF
      beta 3, starting on the day of lesion surgery, did not affect nigral cell death
      or atrophy. These findings support the notion that GDNF, but not TGF-beta 3, is a
      potent neurotrophic factor for nigral dopamine neurons in vivo.

PMID- 7568049
TI  - Parasite abundance and diversity in mammals: correlates with host ecology.
AB  - Fecally dispersed parasites of 12 wild mammal species in Mudumalai Sanctuary,
      southern India, were studied. Fecal propagule densities and parasite diversity
      measures were correlated with host ecological variables. Host species with higher
      predatory pressure had lower parasite loads and parasite diversity. Host body
      weight, home range, population density, gregariousness, and diet did not show
      predicted effects on parasite loads. Measures of alpha diversity were positively
      correlated with parasite abundance and were negatively correlated with beta
      diversity. Based on these data, hypotheses regarding determinants of parasite
      community are discussed.

PMID- 7568048
TI  - Association of a transglutaminase-related antigen with intermediate filaments.
AB  - A mouse monoclonal antibody, G92.1.2, raised against guinea pig liver
      transglutaminase (TGase) recognizes an antigen present in primary mouse dermal
      fibroblasts. A filamentous pattern, bearing remarkable similarity to the vimentin
      intermediate filament (IF) network, is seen when these cells are fixed and
      processed for indirect immunofluorescence with the antibody. Double-label
      immunofluorescence reveals that the antigen reacting with the antibody
      colocalizes precisely with vimentin IF and that this colocalization is retained
      after the treatment of fibroblasts with colchicine, which induces a
      redistribution of the majority of IFs into perinuclear aggregates. These
      morphological observations are further supported by the finding that the protein
      reacting with G92.1.2 is retained in IF-enriched cytoskeletal preparations made
      by using nonionic detergent-containing high ionic strength solutions. Western
      blots of the IF fraction show that G92.1.2 recognizes a major band of
      approximately 280 kDa and does not cross react with vimentin. Furthermore, when
      the antibody is microinjected into live dermal fibroblasts, it causes a collapse
      of the vimentin IF network in the majority of injected cells. The results suggest
      that a form of TGase, or a TGase-related antigen, is closely associated with the
      vimentin IF network of primary cultures of mouse dermal fibroblasts.

PMID- 7568050
TI  - A general genetic approach in Escherichia coli for determining the mechanism(s)
      of action of tumoricidal agents: application to DMP 840, a tumoricidal agent.
AB  - We describe here a simple and easily manipulatable Escherichia coli-based genetic
      system that permits us to identify bacterial gene products that modulate the
      sensitivity of bacteria to tumoricidal agents, such as DMP 840, a
      bisnaphthalimide drug. To the extent that the action of these agents is
      conserved, these studies may expand our understanding agents is conserved, these
      studies may expand our understanding of how the agents work in mammalian cells.
      The approach briefly is to use a library of E. coli genes that are overexpressed
      in a high copy number vector to select bacterial clones that are resistant to the
      cytotoxic effects of drugs. AtolC bacterial mutant is used to maximize
      permeability of cells to hydrophobic organic molecules. By using DMP 840 to model
      the system, we have identified two genes, designated mdaA and mdaB, that impart
      resistance to DMP 840 when they are expressed at elevated levels. mdaB maps to E.
      coli map coordinate 66, is located between the parE and parC genes, and encodes a
      protein of 22 kDa. mdaA maps to E. coli map coordinate 18, is located adjacent to
      the glutaredoxin (grx) gene, and encodes a protein of 24 kDa. Specific and
      regulatable overproduction of both of these proteins correlates with DMP 840
      resistance. Overproduction of the MdaB protein also imparts resistance to two
      mammalian topoisomerase inhibitors, Adriamycin and etoposide. In contrast,
      overproduction of the MdaA protein produces resistance only to Adriamycin. Based
      on its drug-resistance properties and its location between genes that encode the
      two subunits of the bacterial topoisomerase IV, we suggest that mdaB acts by
      modulating topoisomerase IV activity. The location of the mdaA gene adjacent to
      grx suggests it acts by a drug detoxification mechanism.

PMID- 7568051
TI  - Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and
      ameliorates established disease.
AB  - Activated components of the complement system are potent mediators of
      inflammation that may play an important role in numerous disease states. For
      example, they have been implicated in the pathogenesis of inflammatory joint
      diseases including rheumatoid arthritis (RA). To target complement activation in
      immune-mediated joint inflammation, we have utilized monoclonal antibodies (mAbs)
      that inhibit the complement cascade at C5, blocking the generation of the major
      chemotactic and proinflammatory factors C5a and C5b-9. In this study, we
      demonstrate the efficacy of a mAb specific for murine C5 in the treatment of
      collagen-induced arthritis, an animal model for RA. We show that systemic
      administration of the anti-C5 mAb effectively inhibits terminal complement
      activation in vivo and prevents the onset of arthritis in immunized animals. Most
      important, anti-C5 mAb treatment is also highly effective in ameliorating
      established disease. These results demonstrate a critical role for activated
      terminal complement components not only in the induction but also in the
      progression of collagen-induced arthritis and suggest that C5 may be an
      attractive therapeutic target in RA.

PMID- 7568052
TI  - Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and
      in interleukin 4-induced tumor suppression.
AB  - Guinea pig eotaxin is a recently described member of the Cys-Cys family of
      chemokines and is involved in a guinea pig model of asthma. To determine whether
      eotaxin is a distinctive member of this family and to understand its physiologic
      role, we have cloned the mouse eotaxin gene and determined its structure and
      aspects of its biologic function. The sequence relationship between the mouse and
      guinea pig genes indicates that eotaxin is indeed a distinct member of the
      chemokine family. Moreover, murine eotaxin maps to a region of mouse chromosome
      11 that encodes other Cys-Cys chemokines. In addition, recombinant murine eotaxin
      protein has direct chemoattractant properties for eosinophils. The eotaxin gene
      is widely (but not ubiquitously) expressed in normal mice and is strongly induced
      in cultured endothelial cells in response to interferon gamma. Eotaxin is also
      induced locally in response to the transplantation of interleukin 4-secreting
      tumor cells, indicating that it likely contributes to the eosinophil recruitment
      and antitumor effect of interleukin 4. Such responses suggest that eotaxin may be
      involved in multiple inflammatory states.

PMID- 7568055
TI  - Transfection and continuous expression of heterologous genes in the protozoan
      parasite Entamoeba histolytica.
AB  - To provide tools for functional molecular genetics of the protozoan parasite
      Entamoeba histolytica, we investigated the use of the prokaryotic neomycin
      phosphotransferase (NEO) gene as a selectable marker for the transfection of the
      parasite. An Escherichia coli-derived plasmid vector was constructed (pA5'A3'NEO)
      containing the NEO coding region flanked by untranslated 5' and 3' sequences of
      an Ent. histolytica actin gene. Preceding experiments had revealed that amoebae
      are highly sensitive to the neomycin analogue G418 and do not survive in the
      presence of as little as 2 micrograms/ml. Transfection of circular pA5'A3'NEO via
      electroporation resulted in Ent. histolytica trophozoites resistant to G418 up to
      100 micrograms/ml. DNA and RNA analyses of resistant cells indicated that (i) the
      transfected DNA was not integrated into the amoeba genome but was segregated
      episomally, (ii) in the amoebae, the plasmid replicated autonomously, (iii) the
      copy number of the plasmid and the expression of NEO-specific RNA were
      proportional to the amount of G418 used for selection, and (iv) under continuous
      selection, the plasmid was propagated over an observation period of 6 months.
      Moreover, the plasmid could be recloned into E. coli and was found to be
      unrearranged. To investigate the use of pA5'A3'NEO to coexpress other genes in
      Ent. histolytica, a second marker, the prokaryotic chloramphenicol
      acetyltransferase (CAT) gene under control of an Ent. histolytica lectin gene
      promoter was introduced into the plasmid. Transfection of the amoebae with this
      construct also conferred G418 resistance and, in addition, allowed continuous
      expression of CAT activity in quantities corresponding to the amount of G418 used
      for selection. When selection was discontinued, transfected plasmids were lost as
      indicated by an exponential decline of CAT activity in trophozoite extracts.

PMID- 7568053
TI  - Electrophile and antioxidant regulation of enzymes that detoxify carcinogens.
AB  - Detoxication (phase 2) enzymes, such as glutathione S-transferases (GSTs),
      NAD(P)H:(quinone-acceptor) oxidoreductase (QR), and UDP-glucuronsyltransferase,
      are induced in animal cells exposed to a variety of electrophilic compounds and
      phenolic antioxidants. Induction protects against the toxic and neoplastic
      effects of carcinogens and is mediated by activation of upstream electrophile
      responsive/antioxidant-responsive elements (EpRE/ARE). The mechanism of
      activation of these enhancers was analyzed by transient gene expression of growth
      hormone reporter constructs containing a 41-bp region derived from the mouse GST
      Ya gene 5'-upstream region that contains the EpRE/ARE element and of constructs
      in which this element was replaced with either one or two consensus phorbol 12
      tetradecanoate 13-acetate (TPA)-responsive elements (TREs). When these three
      constructs were compared in Hep G2 (human) and Hepa 1c1c7 (murine) hepatoma
      cells, the wild-type sequence was highly activated by diverse inducers, including
      tert-butylhydroquinone, Michael reaction acceptors, 1,2-dithiole-3-thione,
      sulforaphane,2,3-dimercapto-1-propanol, HgCl2, sodium arsenite, and phenylarsine
      oxide. In contrast, constructs with consensus TRE sites were not induced
      significantly. TPA in combination with these compounds led to additive or
      synergistic inductions of the EpRE/ARE construct, but induction of the TRE
      construct was similar to that induced by TPA alone. Transfection of the EpRE/ARE
      reporter construct into F9 cells, which lack endogenous TRE-binding proteins,
      produced large inductions by the same compounds, which also induced QR activity
      in these cells. We conclude that activation of the EpRE/ARE by electrophile and
      antioxidant inducers is mediated by EpRE/ARE-specific proteins.

PMID- 7568054
TI  - Sphingosine: a mediator of acute renal tubular injury and subsequent
      cytoresistance.
AB  - The goal of this study was to determine whether sphingosine and ceramide, second
      messengers derived from sphingolipid breakdown, alter kidney proximal tubular
      cell viability and their adaptive responses to further damage. Adult human kidney
      proximal tubular (HK-2) cells were cultured for 0-20 hr in the presence or
      absence of sphingosine, sphingosine metabolites (sphingosine 1-phosphate,
      dimethylsphingosine), or C2, C8, or C16 ceramide. Acute cell injury was assessed
      by vital dye exclusion and tetrazolium dye transport. Their subsequent impact on
      superimposed ATP depletion/Ca2+ ionophore-induced damage was also assessed.
      Sphingosine (> or = 10 microM), sphingosine 1-phosphate, dimethylsphingosine, and
      selected ceramides (C2 and C8, but not C16) each induced rapid, dose-dependent
      cytotoxicity. This occurred in the absence of DNA laddering or morphologic
      changes of apoptosis, suggesting a necrotic form of cell death. Prolonged
      exposure (20 hr) to subtoxic sphingosine doses (< or = 7.5 microM) induced
      substantial cytoresistance to superimposed ATP depletion/Ca2+ ionophore-mediated
      damage. Conversely, neither short-term sphingosine treatment (< or = 8.5 hr) nor
      20-hr exposures to any of the above sphingosine/ceramide derivatives/metabolites
      or various free fatty acids reproduced this effect. Sphingosine-induced
      cytoresistance was dissociated from the extent of cytosolic Ca2+ loading (indo-1
      fluorescence), indicating a direct increase in cell resistance to attack. We
      conclude that sphingosine can exert dual effects on proximal renal tubular
      viability: in high concentrations it induces cell necrosis, whereas in low doses
      it initiates a cytoresistant state. These results could be reproduced in human
      foreskin fibroblasts, suggesting broad-based relevance to the area of acute cell
      injury and repair.

PMID- 7568056
TI  - High-affinity RNA-binding domains of alfalfa mosaic virus coat protein are not
      required for coat protein-mediated resistance.
AB  - A virus-based vector was used for the transient expression of the alfalfa mosaic
      virus coat protein (CP) gene in protoplasts and plants. The accumulation of wild
      type CP conferred strong protection against subsequent alfalfa mosaic virus
      infection, enabling the efficacy of CP mutants to be determined without
      developing transgenic plants. Expression of the CP mRNA alone without CP
      accumulation conferred weaker protection against infection. The activity of the N
      terminal mutant CPs in protection did not correlate with their activities in
      genome activation. The activity of a C-terminal mutant suggested that
      encapsidation did not have a role in protection. Our results indicate that
      interaction of the CP with alfalfa mosaic virus RNA is not important in
      protection, thereby leaving open the possibility that interactions with host
      factors lead to protection.

PMID- 7568057
TI  - Nodulating strains of Rhizobium loti arise through chromosomal symbiotic gene
      transfer in the environment.
AB  - Rhizobia were isolated from nodules off a stand of Lotus corniculatus established
      with a single inoculant strain, ICMP3153, 7 years earlier in an area devoid of
      naturalized Rhizobium loti. The isolates showed diversity in growth rate, Spe I
      fingerprint of genomic DNA, and hybridization pattern to genomic DNA probes. The
      19% of isolates that grew at the same rate as strain ICMP3153 were the only
      isolates that had the same fingerprint as strain ICMP3153. Sequencing of part of
      the 16S rRNA gene of several diverse isolates confirmed that they were not
      derived from the inoculant strain. Nevertheless, all non-ICMP3153 strains gave
      EcoRI and Spe I hybridization patterns identical to ICMP3153 when hybridized to
      nodulation gene cosmids. Hybridization of digests generated by the very rare
      cutting enzyme Swa I revealed that the symbiotic DNA region (at least 105 kb) was
      chromosomally integrated in the strains. The results suggest that the diverse
      strains arose by transfer of chromosomal symbiotic genes from ICMP3153 to
      nonsymbiotic rhizobia in the environment.

PMID- 7568058
TI  - Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking
      acetaldehyde metabolism.
AB  - Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial
      aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by
      Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and
      calcium citrate carbimide (Temposil), have also been shown to suppress ethanol
      intake of laboratory animals and are thought to act by inhibiting the metabolism
      of acetaldehyde produced from ingested ethanol. To determine whether or not
      daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin
      treated hamsters was measured after the administration of a test dose of ethanol.
      Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (>
      70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism.
      In contrast, after administration of the same ethanol dose, plasma acetaldehyde
      concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than
      that of the control. In vitro, daidzin suppresses hamster liver mitochondria
      catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 microM,
      which is substantially lower than the daidzin concentration (70 microM) found in
      the liver mitochondria of daidzin-treated hamsters. These results indicate that
      (i) the action of daidzin differs from that proposed for the classic, broad
      acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive
      mitochondrial ALDH is not the one and only enzyme that is essential for
      acetaldehyde metabolism in golden hamsters.

PMID- 7568059
TI  - Single-site cleavage in the 5'-untranslated region of Leishmaniavirus RNA is
      mediated by the viral capsid protein.
AB  - Leishmaniavirus (LRV) is a double-stranded RNA virus that persistently infects
      the protozoan parasite Leishmania. LRV produces a short RNA transcript,
      corresponding to the 5' end of positive-sense viral RNA, both in vivo and in in
      vitro polymerase assays. The short transcript is generated by a single site
      specific cleavage event in the 5' untranslated region of the 5.3-kb genome. This
      cleavage event can be reproduced in vitro with purified viral particles and a
      substrate RNA transcript possessing the viral cleavage site. A region of
      nucleotides required for cleavage was identified by analyzing the cleavage sites
      yielding the short transcripts of various LRV isolates. A 6-nt deletion at this
      cleavage site completely abolished RNA processing. In an in vitro cleavage assay,
      baculovirus-expressed capsid protein possessed an endonuclease activity identical
      to that of native virions, showing that the viral capsid protein is the RNA
      endonuclease. Identification of the LRV capsid protein as an RNA endonuclease is
      unprecedented among known viral capsid proteins.

PMID- 7568060
TI  - Targeting cancer micrometastases with monoclonal antibodies: a binding-site
      barrier.
AB  - Monoclonal antibodies penetrate bulky tumors poorly after intravenous
      administration, in part because of specific binding to the target antigen.
      Experiments presented here demonstrate an analogous phenomenon in
      micrometastases; poor antibody penetration, attributable to a "binding-site
      barrier" phenomenon, can be seen in guinea pig micrometastases as small as 300
      microns in diameter. Increasing the dose of antibody can partially overcome this
      limitation, but at a cost in specificity.

PMID- 7568062
TI  - The recombinant DNA controversy: twenty years later.

PMID- 7568061
TI  - Fusogenic selectivity of the envelope glycoprotein is a major determinant of
      human immunodeficiency virus type 1 tropism for CD4+ T-cell lines vs. primary
      macrophages.
AB  - We investigated the relationship between the fusion selectivity of the envelope
      glycoprotein (env) and the tropism of different human immunodeficiency virus type
      1 (HIV-1) isolates for CD4+ human T-cell lines vs. primary macrophages.
      Recombinant vaccinia viruses were prepared encoding the envs from several well
      characterized HIV-1 isolates with distinct cytotropisms. Cells expressing the
      recombinant envs were mixed with various CD4+ partner cell types; cell fusion was
      monitored by a quantitative reporter gene assay and by syncytia formation. With
      CD4+ continuous cell lines as partners (T-cell lines, HeLa cells expressing
      recombinant CD4), efficient fusion occurred with the envs from T-cell line-tropic
      isolates (IIIB, LAV, SF2, and RF) but not with the envs from macrophage-tropic
      isolates (JR-FL, SF162, ADA, and Ba-L). The opposite selectivity pattern was
      observed with primary macrophages as cell partners; stronger fusion occurred with
      the envs from the macrophage-tropic than from the T-cell line-tropic isolates.
      All the envs showed fusion activity with peripheral blood mononuclear cells as
      partners, consistent with the ability of this cell population to support
      replication of all the corresponding HIV-1 isolates. These fusion selectivities
      were maintained irrespective of the cell type used to express env, thereby
      excluding a role for differential host cell modification. We conclude that the
      intrinsic fusion selectivity of env plays a major role in the tropism of a HIV-1
      isolate for infection of CD4+ T-cell lines vs. primary macrophages, presumably by
      determining the selectivity of virus entry and cell fusion.

PMID- 7568063
TI  - Molecular organization of histidine-tagged biomolecules at self-assembled lipid
      interfaces using a novel class of chelator lipids.
AB  - In molecular biology, the expression of fusion proteins is a very useful and well
      established technique for the identification and one-step purification of gene
      products. Even a short fused sequence of five or six histidines enables proteins
      to bind to an immobilized metal ion chelate complex. By synthesis of a class of
      chelator lipids, we have transferred this approach to the concept of self
      assembly. The specific interaction and lateral organization of a fluorescent
      fusion molecule containing a C-terminal oligohistidine sequence was studied by
      film balance techniques in combination with epifluorescence microscopy. Due to
      the phase behavior of the various lipid mixtures used, the chelator lipids can be
      laterally structured, generating two-dimensional arrays of histidine-tagged
      biomolecules. Because of the large variety of fusion proteins already available,
      this concept represents a powerful technique for orientation and organization of
      proteins at lipid interfaces with applications in biosensing,
      biofunctionalization of nanostructured interfaces, two-dimensional
      crystallization, and studies of lipid-anchored proteins.

PMID- 7568064
TI  - Induction of a retinoblastoma phosphatase activity by anticancer drugs
      accompanies p53-independent G1 arrest and apoptosis.
AB  - DNA-damaging agents induce accumulation of the tumor suppressor and G1 checkpoint
      protein p53, leading cells to either growth arrest in G1 or apoptosis (programmed
      cell death). The p53-dependent G1 arrest involves induction of p21 (also called
      WAF1/CIP1/SDI1), which prevents cyclin kinase-mediated phosphorylation of
      retinoblastoma protein (RB). Recent studies suggest a p53-independent G1
      checkpoint as well; however, little is known about its molecular mechanisms. We
      report that induction of a protein-serine/threonine phosphatase activity by DNA
      damage signals is at least one of the mechanisms responsible for p53-independent,
      RB-mediated G1 arrest and consequent apoptosis. When two p53-null human leukemic
      cell lines (HL-60 and U-937) were treated with a variety of anticancer agents, RB
      became hypophosphorylated, accompanied with G1 arrest. This was followed
      immediately (in less than 30 min) by apoptosis, as determined by the accumulation
      of pre-G1 apoptotic cells and the internucleosomal fragmentation of DNA. Addition
      of calyculin A or okadaic acid (specific serine/threonine phosphatase inhibitors)
      or zinc chloride (apoptosis inhibitor) prevented the G1 arrest- and apoptosis
      specific RB dephosphorylation. The levels of cyclin E- and cyclin A-associated
      kinase activities remained high during RB dephosphorylation, supporting the
      involvement of a chemotherapy-induced serine/threonine phosphatase(s) rather than
      p21. Furthermore, the induced phosphatase activity coimmunoprecipitated with the
      hyperphosphorylated RB and was active in a cell-free system that reproduced the
      growth arrest- and apoptosis-specific RB dephosphorylation, which was inhibitable
      by calyculin A but not zinc. We propose that the RB phosphatase(s) might be one
      of the p53-independent G1 checkpoint regulators.

PMID- 7568065
TI  - [Leu5]enkephalin-encoding sequences are targets for a specific DNA-binding
      factor.
AB  - A DNA-binding factor with high affinity and specificity for the [Leu5]enkephalin
      encoding sequences in the prodynorphin and proenkephalin genes has been
      characterized. The factor has the highest affinity for the [Leu5]-enkephalin
      encoding sequence in the dynorphin B-encoding region of the prodynorphin gene,
      has relatively high affinity for other [Leu5]enkephalin-encoding sequences in the
      prodynorphin and proenkephalin genes, but has no apparent affinity for similar
      DNA sequences coding for [Met5]-enkephalin in the prodynorphin or
      proopiomelanocortin genes. The factor has been named [Leu5]enkephalin-encoding
      sequence DNA-binding factor (LEF). LEF has a nuclear localization and is composed
      of three subunits of about 60, 70, and 95 kDa, respectively. The highest levels
      were observed in rat testis, cerebellum, and spleen and were generally higher in
      late embryonal compared to newborn or adult animals. LEF activity was also
      recorded in human clonal tumor cell lines. LEF inhibited the transcription of
      reporter genes in artificial gene constructs where a [Leu5]enkephalin-encoding
      DNA fragment had been inserted between the transcription initiation site and the
      coding region of the reporter genes. These observations suggest that the
      [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes
      also have regulatory functions realized through interaction with a specific DNA
      binding factor.

PMID- 7568066
TI  - Kinetic traps in lysozyme folding.
AB  - Folding of lysozyme from hen egg white was investigated by using interrupted
      refolding experiments. This method makes use of a high energy barrier between the
      native state and transient folding intermediates, and, in contrast to
      conventional optical techniques, it enables one to specifically monitor the
      amount of native molecules during protein folding. The results show that under
      strongly native conditions lysozyme can refold on parallel pathways. The major
      part of the lysozyme molecules (86%) refold on a slow kinetic pathway with well
      populated partially folded states. Additionally, 14% of the molecules fold
      faster. The rate constant of formation of native molecules on the fast pathway
      corresponds well to the rate constant expected for folding to occur by a two
      state process without any detectable intermediates. The results suggest that
      formation of the native state for the major fraction of lysozyme molecules is
      retarded compared with the direct folding process. Partially structured
      intermediates that transiently populate seem to be kinetically trapped in a
      conformation that can only slowly reach the native structure.

PMID- 7568067
TI  - Regulated expression of the obese gene product (leptin) in white adipose tissue
      and 3T3-L1 adipocytes.
AB  - A mutation within the obese gene was recently identified as the genetic basis for
      obesity in the ob/ob mouse. The obese gene product, leptin, is a 16-kDa protein
      expressed predominantly in adipose tissue. Consistent with leptin's postulated
      role as an extracellular signaling protein, human embryonic kidney 293 cells
      transfected with the obese gene secreted leptin with minimal intracellular
      accumulation. Upon differentiation of 3T3-L1 preadipocytes into adipocytes, the
      leptin mRNA was expressed concomitant with mRNAs encoding adipocyte marker
      proteins. A factor(s) present in calf serum markedly activated expression of
      leptin by fully differentiated 3T3-L1 adipocytes. A 16-hr fast decreased (by
      approximately 85%) the leptin mRNA level of adipose tissue of lean (ob/+ or +/+)
      mice but had no effect on the approximately 4-fold higher level in obese (ob/ob)
      littermates. Since the mutation at the ob locus fails to produce the functional
      protein, yet its cognate mRNA is overproduced, it appears that leptin is
      necessary for its own downregulation. Leptin mRNA was also suppressed in adipose
      tissue of rats during a 16-hr fast and was rapidly induced during a 4-hr
      refeeding period. Insulin deficiency provoked by streptozotocin also markedly
      down-regulated leptin mRNA and this suppression was rapidly reversed by insulin.
      These results suggest that insulin may regulate the expression of leptin.

PMID- 7568068
TI  - Impaired cell volume regulation in intestinal crypt epithelia of cystic fibrosis
      mice.
AB  - Cystic fibrosis is a disease characterized by abnormalities in the epithelia of
      the lungs, intestine, salivary and sweat glands, liver, and reproductive systems,
      often as a result of inadequate hydration of their secretions. The primary defect
      in cystic fibrosis is the altered activity of a cAMP-activated Cl- channel, the
      cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it
      is not clear how a defect in the CFTR Cl- channel function leads to the observed
      pathological changes. Although much is known about the structural properties and
      regulation of the CFTR, little is known of its relationship to cellular functions
      other than the cAMP-dependent Cl- secretion. Here we report that cell volume
      regulation after hypotonic challenge is also defective in intestinal crypt
      epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of
      the regulatory volume decrease in CFTR -/- crypts appears to be related to the
      inability of a K+ conductance to provide a pathway for the exit of this cation
      during the volume adjustments. This provides evidence that the lack of CFTR
      protein may have additional consequences for the cellular function other than the
      abnormal cAMP-mediated Cl- secretion.

PMID- 7568069
TI  - Studies of the lamin proteinase reveal multiple parallel biochemical pathways
      during apoptotic execution.
AB  - Although specific proteinases play a critical role in the active phase of
      apoptosis, their substrates are largely unknown. We previously identified
      poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for
      proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have
      used a cell-free system to characterize proteinase(s) that cleave the nuclear
      lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a
      second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of
      sensitivity to specific inhibitors that is distinct from the PARP proteinase.
      Thus, multiple ICE-like enzymes are required for apoptotic events in these cell
      free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl
      ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin
      into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved
      to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the
      fragmentation nuclease function in independent parallel pathways during the final
      stages of apoptotic execution. Neither pathway alone is sufficient for completion
      of nuclear apoptosis. Instead, the various activities cooperate to drive the
      disassembly of the nucleus.

PMID- 7568071
TI  - Homeologous recombination and mismatch repair during transformation in
      Streptococcus pneumoniae: saturation of the Hex mismatch repair system.
AB  - The ability of the Hex generalized mismatch repair system to prevent
      recombination between partially divergent (also called homeologous) sequences
      during transformation in Streptococcus pneumoniae was investigated. By using as
      donor in transformation cloned fragments 1.7-17.5% divergent in DNA sequence from
      the recipient, it was observed that the Hex system prevents chromosomal
      integration of the least and the most divergent fragments but frequently fails to
      do so for other fragments. In the latter case, the Hex system becomes saturated
      (inhibited) due to an excess of mismatches: it is unable to repair a single
      mismatch located elsewhere on the chromosome. Further investigation with
      chromosomal donor DNA, carrying only one genetically marked divergent region,
      revealed that a single divergent fragment can lead to saturation of the Hex
      system. Increase in cellular concentration of either HexA, the MutS homologue
      that binds mismatches, or HexB, the MutL homologue for which the essential role
      in repair as yet remains obscure, was shown to restore repair ability in
      previously saturating conditions. Investigation of heterospecific transformation
      by chromosomal DNA from two related streptococcal species, Streptococcus oralis
      and Streptococcus mitis, also revealed complete saturation of the Hex system.
      Therefore the Hex system is not a barrier to interspecies recombination in S.
      pneumoniae. These results are discussed in light of those described for the Mut
      system of Escherichia coli.

PMID- 7568070
TI  - Maintenance of pre-mRNA secondary structure by epistatic selection.
AB  - Linkage disequilibrium between polymorphisms in a natural population may result
      from various evolutionary forces, including random genetic drift due to sampling
      of gametes during reproduction, restricted migration between subpopulations in a
      subdivided population, or epistatic selection. In this report, we present
      evidence that the majority of significant linkage disequilibria observed in
      introns of the alcohol dehydrogenase locus (Adh) of Drosophila pseudoobscura are
      due to epistatic selection maintaining secondary structure of precursor mRNA (pre
      mRNA). Based on phylogenetic-comparative analysis and a likelihood approach, we
      propose secondary structure models of Adh pre-mRNA for the regions of the adult
      intron and intron 2 where clustering of linkage disequilibria has been observed.
      Furthermore, we applied the likelihood ratio test to the phylogenetically
      predicted secondary structure in intron 1. In contrast to the other two
      structures, polymorphisms associated with the more conserved stem-loop structure
      of intron 1 are in low frequency, and linkage disequilibria have not been
      observed. These findings are qualitatively consistent with a model of
      compensatory fitness interactions. This model assumes that mutations disrupting
      pairing in a secondary structural element are individually deleterious if they
      destabilize a functionally important structure; a second "compensatory" mutation,
      however, may restabilize the structure and restore fitness.

PMID- 7568072
TI  - Conjugates of folate and anti-T-cell-receptor antibodies specifically target
      folate-receptor-positive tumor cells for lysis.
AB  - High-affinity folate receptors (FRs) are expressed at elevated levels on many
      human tumors. Bispecific antibodies that bind the FR and the T-cell receptor
      (TCR) mediate lysis of these tumor cells by cytotoxic T lymphocytes. In this
      report, conjugates that consist of folate covalently linked to anti-TCR
      antibodies are shown to be potent in mediating lysis of tumor cells that express
      either the alpha or beta isoform of the FR. Intact antibodies with an average of
      five folate per molecule exhibited high affinity for FR+ tumor cells but did not
      bind to FR- tumor cells. Lysis of FR+ cell lines could be detected at
      concentrations as low as 1 pM (approximately 0.1 ng/ml), which was 1/1000th the
      concentration required to detect binding to the FR+ cells. Various FR+ mouse
      tumor cell lines could be targeted with each of three different anti-TCR
      antibodies that were tested as conjugates. The antibodies included 1B2, a
      clonotypic antibody specific for the cytotoxic T cell clone 2C; KJ16, an anti-V
      beta 8 antibody; and 2C11, an anti-CD3 antibody. These antibodies differ in
      affinities by up to 100-fold, yet the cytolytic capabilities of the
      folate/antibody conjugates differed by no more than 10-fold. The reduced size (in
      comparison with bispecific antibodies) and high affinity of folate conjugates
      suggest that they may be useful as immunotherapeutic agents in targeting tumors
      that express folate receptors.

PMID- 7568073
TI  - Subunit-specific functions of N-linked oligosaccharides in human thyrotropin:
      role of terminal residues of alpha- and beta-subunit oligosaccharides in
      metabolic clearance and bioactivity.
AB  - The recombinant human thyroid stimulating hormone (rhTSH) containing
      oligosaccharides terminated with NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc beta 1
      showed higher in vivo activity and lower metabolic clearance rate (MCR) than
      pituitary human TSH (phTSH), which contains oligosaccharides terminating
      predominantly in SO(4)4GalNAc(beta 1-4)GlcNAc beta 1. To elucidate the relative
      contribution of the sulfated and sialylated carbohydrate chains of each subunit
      in the MCR and bioactivity of the hormone, the alpha and beta subunits of phTSH,
      rhTSH, and enzymatically desialylated rhTSH (asialo-rhTSH; asrhTSH) were
      isolated, their oligosaccharides were analyzed, and the respective subunits were
      dimerized in various combinations. The hybrids containing alpha subunit from
      phTSH or asrhTSH showed higher in vitro activity than those with alpha subunit
      from rhTSH, indicating that sialylation of alpha but not beta subunit attenuates
      the intrinsic activity of TSH. In contrast, hybrids with beta subunit from rhTSH
      displayed lower MCR compared to those with beta subunit from phTSH. The phTSH
      alpha-rhTSH beta hybrid had the highest in vivo bioactivity followed by rhTSH
      alpha-rhTSH beta, rhTSH alpha-phTSH beta, phTSH alpha-phTSH beta, and asrhTSH
      dimers. These differences indicated that hybrids with beta subunit from rhTSH
      displayed the highest in vivo activity and relatively low MCR, probably due to
      higher sialylation, more multiantennary structure, and/or the unique location of
      the beta-subunit oligosaccharide chain in the molecule. Thus, the N-linked
      oligosaccharides of the beta subunit of glycoprotein hormones have a more
      pronounced role than those from the alpha subunit in the metabolic clearance and
      thereby in the in vivo bioactivity. In contrast, the terminal residues of alpha
      subunit oligosaccharides have a major impact on TSH intrinsic potency.

PMID- 7568074
TI  - High-affinity neuropeptide Y receptor antagonists.
AB  - Neuropeptide Y (NPY) is one of the most abundant peptide transmitters in the
      mammalian brain. In the periphery it is costored and coreleased with
      norepinephrine from sympathetic nerve terminals. However, the physiological
      functions of this peptide remain unclear because of the absence of specific high
      affinity receptor antagonists. Three potent NPY receptor antagonists were
      synthesized and tested for their biological activity in in vitro, ex vivo, and in
      vivo functional assays. We describe here the effects of these antagonists
      inhibiting specific radiolabeled NPY binding at Y1 and Y2 receptors and
      antagonizing the effects of NPY in human erythroleukemia cell intracellular
      calcium mobilization perfusion pressure in the isolated rat kidney, and mean
      arterial blood pressure in anesthetized rats.

PMID- 7568076
TI  - Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in
      vitro.
AB  - Neuronal proliferation, migration, and differentiation are regulated by the
      sequential expression of particular genes at specific stages of development. Such
      processes rely on differential gene expression modulated through second-messenger
      systems. Early postnatal mouse cerebellar granule cells migrate into the internal
      granular layer and acquire differentiated properties. The neurotransmitter
      glutamate has been shown to play an important role in this developmental process.
      We show here by immunohistochemistry that the RelA subunit of the transcription
      factor NF-kappa B is present in several areas of the mouse brain. Moreover,
      immunofluorescence microscopy and electrophoretic mobility-shift assay
      demonstrate that in cerebellar granule cell cultures derived from 3- to 7-day-old
      mice, glutamate specifically activates the transcription factor NF-kappa B, as
      shown by binding of nuclear extract proteins to a synthetic oligonucleotide
      reproducing the kappa B site of human immunodeficiency virus. The use of
      different antagonists of the glutamate recpetors indicates that the effect of
      glutamate occurs mainly via N-methyl-D-aspartate (NMDA)-receptor activation,
      possibly as a result of an increase in intracellular Ca2+. The synaptic
      specificity of the effect is strongly suggested by the observation that glutamate
      failed to activate NF-kappa B in astrocytes, while cytokines, such as interleukin
      1 alpha and tumor necrosis factor alpha, did so. The effect of glutamate appears
      to be developmentally regulated. Indeed, NF-kappa B is found in an inducible form
      in the cytoplasm of neurons of 3- to 7-day-old mice but is constitutively
      activated in the nuclei of neurons derived from older pups (8-10 days postnatal).
      Overall, these observations suggest the existence of a new pathway of trans
      synaptic regulation of gene expression.

PMID- 7568077
TI  - Telomerase activity in normal and malignant hematopoietic cells.
AB  - Bone marrow and peripheral blood leukocytes from 19 leukemia patients were found
      to contain telomerase activity detectable by a PCR-based assay. Telomerase was
      also detectable in nonmalignant bone marrow and peripheral blood leukocytes from
      normal donors, including fractions enriched for granulocytes, T lymphocytes, and
      monocytes/B cells. Semiquantitative comparison revealed considerable overlap
      between telomerase activities in samples from normal subjects and leukemia
      patients, confounding evaluation of the role of telomerase in this disease. These
      data indicate that human telomerase is not restricted to immortal cells and
      suggest that the somatic expression of this enzyme may be more widespread than
      was previously inferred from the decline of human telomeres.

PMID- 7568075
TI  - Molecular and biochemical characterization of dNOS: a Drosophila Ca2+/calmodulin
      dependent nitric oxide synthase.
AB  - Nitric oxide (NO) is an intercellular messenger involved with various aspects of
      mammalian physiology ranging from vasodilation and macrophage cytotoxicity to
      neuronal transmission. NO is synthesized from L-arginine by NO synthase (NOS).
      Here, we report the cloning of a Drosophila NOS gene, dNOS, located at
      cytological position 32B. The dNOS cDNA encodes a protein of 152 kDa, with 43%
      amino acid sequence identity to rat neuronal NOS. Like mammalian NOSs, DNOS
      protein contains putative binding sites for calmodulin, FMN, FAD, and NADPH. DNOS
      activity is Ca2+/calmodulin dependent when expressed in cell culture. An
      alternative RNA splicing pattern also exists for dNOS, which is identical to that
      for vertebrate neuronal NOS. These structural and functional observations
      demonstrate remarkable conservation of NOS between vertebrates and invertebrates.

PMID- 7568079
TI  - Glial cell line-derived neurotrophic factor promotes the survival and morphologic
      differentiation of Purkinje cells.
AB  - Glial cell line-derived neurotrophic factor (GDNF) promotes survival of midbrain
      dopaminergic neurons and motoneurons. Expression of GDNF mRNA in cerebellum
      raises the possibility that cells within this structure might also respond to
      GDNF. To examine potential trophic activities of GDNF, dissociated cultures of
      gestational day 18 rat cerebellum were grown for < or = 21 days in the presence
      of factor. GDNF increased Purkinje cell number without affecting the overall
      number of neurons or glial cells. A maximal response (50% above control) was
      elicited with GDNF at 1 pg/ml. Effects of GDNF on Purkinje cell differentiation
      were examined by scoring the morphologic maturation of cells in treated and
      control cultures. GDNF increased the proportion of Purkinje cells that displayed
      relatively mature morphologies, characterized by dendritic thickening and the
      development of spines and filopodial extensions. Morphologic maturation of the
      overall neuronal population was unaffected. In sum, our data indicate that GDNF
      is a potent survival and differentiation factor for Purkinje cells, the efferent
      neurons of cerebellar cortex. Together with its other actions, these findings
      raise the possibility that GDNF might be a critical trophic factor at multiple
      loci in neuronal circuits that control motor function.

PMID- 7568078
TI  - Conservation and function of the transcriptional regulatory protein Runt.
AB  - A phylogenetic approach was used to identify conserved regions of the
      transcriptional regulator Runt. Alignment of the deduced protein sequences from
      Drosophila melanogaster, Drosophila pseudoobscura, and Drosophila virilis
      revealed eight blocks of high sequence homology separated by regions with little
      or no homology. The largest conserved block contains the Runt domain, a DNA and
      protein binding domain conserved in a small family of mammalian transcription
      factors. The functional properties of the Runt domain from the D. melanogaster
      gene and the human AML1 (acute myeloid leukemia 1) gene were compared in vitro
      and in vivo. Electrophoretic mobility-shift assays with Runt/AML1 chimeras
      demonstrated that the different DNA binding properties of Runt and AML1 are due
      to differences within their respective Runt domains. Ectopic expression
      experiments indicated that proteins containing the AML1 Runt domain function in
      Drosophila embryos and that sequences outside of this domain are important in
      vivo.

PMID- 7568081
TI  - Receptor-G protein coupling is established by a potential conformational switch
      in the beta gamma complex.
AB  - Receptor-G protein interaction is characterized by cycles of association and
      dissociation. We present evidence which indicates that during receptor-G protein
      interaction, the C-terminal tail of the G protein gamma subunit, which is masked
      in the beta gamma complex, is exposed and establishes high-affinity contact with
      the receptor. This potential conformational switch provides a mechanism to
      regulate receptor-G protein coupling. This switch may also be significant for the
      role of the beta gamma complex in regulation of effector function.

PMID- 7568080
TI  - Cooperative transcriptional activity of Jun and Stat3 beta, a short form of
      Stat3.
AB  - To identify proteins that regulate the transcriptional activity of c-Jun, we have
      used the yeast two-hybrid screen to detect mammalian polypeptides that might
      interact functionally with the N-terminal segment of c-Jun, a known regulatory
      region. Among the proteins identified is a short form of Stat3 (designated Stat3
      beta). Stat3 beta is missing the 55 C-terminal amino acid residues of the long
      form (Stat3 alpha) and has 7 additional amino acid residues at its C terminus. In
      the absence of added cytokines, expression of Stat3 beta (but not Stat3 alpha) in
      transfected cells activated a promoter containing the interleukin 6 responsive
      element of the rat alpha 2-macroglobulin gene; coexpression of Stat3 beta and c
      Jun led to enhanced cooperative activation of the promoter. Nuclear extracts of
      cells transfected with a Stat3 beta expression plasmid formed a complex with an
      oligonucleotide containing a Stat3 binding site, whereas extracts of cells
      transfected with a Stat3 alpha plasmid did not. We conclude that there is a short
      form of Stat3 (Stat3 beta), that Stat3 beta is transcriptionally active under
      conditions where Stat3 alpha is not, and that Stat3 beta and c-Jun are capable of
      cooperative activation of certain promoters.

PMID- 7568083
TI  - Tyrosine phosphorylation of protein kinase C-delta in response to the activation
      of the high-affinity receptor for immunoglobulin E modifies its substrate
      recognition.
AB  - The delta isoform of protein kinase C is phosphorylated on tyrosine in response
      to antigen activation of the high-affinity receptor for immunoglobulin E. While
      protein kinase C-delta associates with and phosphorylates this receptor,
      immunoprecipitation of the receptor revealed that little, if any, tyrosine
      phosphorylated protein kinase C-delta is receptor associated. In vitro kinase
      assays with immunoprecipitated tyrosine-phosphorylated protein kinase C-delta
      showed that the modified enzyme had diminished activity toward the receptor gamma
      chain peptide as a substrate but not toward histones or myelin basic protein
      peptide. We propose a model in which the tyrosine phosphorylation of protein
      kinase C-delta regulates the kinase specificity toward a given substrate. This
      may represent a general mechanism by which in vivo protein kinase activities are
      regulated in response to external stimuli.

PMID- 7568082
TI  - An alternatively spliced form of the transcription factor Sp1 containing only a
      single glutamine-rich transactivation domain.
AB  - Protein-protein interactions involving specific transactivation domains play a
      central role in gene transcription and its regulation. The promoter-specific
      transcription factor Sp1 contains two glutamine-rich transcriptional activation
      domains (A and B) that mediate direct interactions with the transcription factor
      TFIID complex associated with RNA polymerase II and synergistic effects involving
      multiple Sp1 molecules. In the present study, we report the complementary DNA
      sequence for an alternatively spliced form of mouse Sp1 (mSp1-S) that lacks one
      of the two glutamine-rich activation regions present in the full-length protein.
      Corresponding transcripts were identified in mouse tissues and cell lines, and an
      Sp1-related protein identical in size to that predicted for mSp1-S was detected
      in mouse nuclear extracts. Cotransfection analysis revealed that mSp1-S lacks
      appreciable activity at promoters containing a single Sp1 response element but is
      active when multiple Sp1 sites are present, suggesting synergistic interactions
      between multiple mSp1-S molecules. The absence of a single glutamine-rich domain
      does not fully explain the properties of the smaller protein and indicates that
      additional structural features account for its unique transcriptional activity.
      The functional implications of this alternatively spliced form of Sp1 are
      discussed.

PMID- 7568084
TI  - Redirecting the specificity of ubiquitination by modifying ubiquitin-conjugating
      enzymes.
AB  - Depletion of specific cellular proteins is a powerful tool in biological research
      and has many medical and agricultural benefits. In contrast to genetic methods
      currently available to attenuate protein levels, we describe an alternative
      approach that redirects the ubiquitin-dependent proteolytic pathway to facilitate
      specific proteolytic removal. Degradation via the ubiquitin pathway requires the
      prior attachment of multiple ubiquitins to the target protein. This attachment is
      accomplished, in part, by a family of enzymes designated E2s (or ubiquitin
      conjugating enzymes), some of which use domains near their C termini for target
      recognition. Here, we demonstrate that E2 target recognition can be redefined by
      engineering E2s to contain appropriate protein-binding peptides fused to their C
      termini. In five dissimilar examples, chimeric E2s were created that recognized
      and ubiquitinated their respective binding partners with high specificity. We
      also show that ubiquitination of one protein targeted by this method led to its
      ATP-dependent degradation in vitro. Thus, by exploiting interacting domains
      derived from natural and synthetic ligands, it may be possible to design E2s
      capable of directing the selective removal of many intracellular proteins.

PMID- 7568085
TI  - A nuclear gene of eubacterial origin in Euglena gracilis reflects cryptic
      endosymbioses during protist evolution.
AB  - Genes for glycolytic and Calvin-cycle glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) of higher eukaryotes derive from ancient gene duplications which occurred
      in eubacterial genomes; both were transferred to the nucleus during the course of
      endosymbiosis. We have cloned cDNAs encoding chloroplast and cytosolic GAPDH from
      the early-branching photosynthetic protist Euglena gracilis and have determined
      the structure of its nuclear gene for cytosolic GAPDH. The gene contains four
      introns which possess unusual secondary structures, do not obey the GT-AG rule,
      and are flanked by 2- to 3-bp direct repeats. A gene phylogeny for these
      sequences in the context of eubacterial homologues indicates that euglenozoa,
      like higher eukaryotes, have obtained their GAPDH genes from eubacteria via
      endosymbiotic (organelle-to-nucleus) gene transfer. The data further suggest that
      the early-branching protists Giardia lamblia and Entamoeba histolytica--which
      lack mitochondria--and portions of the trypanosome lineage have acquired GAPDH
      genes from eubacterial donors which did not ultimately give rise to contemporary
      membrane-bound organelles. Evidence that "cryptic" (possibly ephemeral)
      endosymbioses during evolution may have entailed successful gene transfer is
      preserved in protist nuclear gene sequences.

PMID- 7568086
TI  - Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed
      to a supraphysiologic glucose concentration is associated with loss of STF-1
      transcription factor expression.
AB  - Chronic exposure of HIT-T15 beta cells to elevated glucose concentrations leads
      to decreased insulin gene transcription. The reduction in expression is
      accompanied by diminished binding of a glucose-sensitive transcription factor
      (termed GSTF) that interacts with two (A+T)-rich elements within the 5' flanking
      control region of the insulin gene. In this study we examined whether GSTF
      corresponds to the recently cloned insulin gene transcription factor STF-1, a
      homeodomain protein whose expression is restricted to the nucleus of endodermal
      cells of the duodenum and pancreas. We found that an affinity-purified antibody
      recognizing STF-1 supershifted the GSTF activator complex formed from HIT-T15
      extracts. In addition, we demonstrated a reduction in STF-1 mRNA and protein
      levels that closely correlated with the change in GSTF binding in HIT-T15 cells
      chronically cultured under supraphysiologic glucose concentrations. The reduction
      in STF-1 expression in these cells could be accounted for by a change in the rate
      of STF-1 gene transcription, suggesting a posttranscriptional control mechanism.
      In support of this hypothesis, no STF-1 mRNA accumulated in HIT-T15 cells
      passaged in 11.1 mM glucose. The only RNA species detected was a 6.4-kb STF-1 RNA
      species that hybridized with 5' and 3' STF-1-specific cDNA probes. We suggest
      that the 6.4-kb RNA represents an STF-1 mRNA precursor and that splicing of this
      RNA is defective in these cells. Overall, this study suggests that reduced
      expression of a key transcriptional regulatory factor, STF-1, contributes to the
      decrease in insulin gene transcription in HIT-T15 cells chronically cultured in
      supraphysiologic glucose concentration.

PMID- 7568089
TI  - NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component
      of Alzheimer disease amyloid, binds A beta and stimulates A beta aggregation.
AB  - NACP, a 140-amino acid presynaptic protein, is the precursor of NAC [the non
      amyloid beta/A4 protein (A beta) component of Alzheimer disease (AD) amyloid], a
      peptide isolated from and immunologically localized to brain amyloid of patients
      afflicted with AD. NACP produced in Escherichia coli bound to A beta peptides,
      the major component of AD amyloid. NACP bound to A beta 1-38 and A beta 25-35
      immobilized on nitrocellulose but did not bind to A beta 1-28 on the filter under
      the same conditions. NACP binding to A beta 1-38 was abolished by addition of A
      beta 25-35 but not by A beta 1-28, suggesting that the hydrophobic region of the
      A beta peptide is critical to this binding. NACP-112, a shorter splice variant of
      NACP containing the NAC sequence, bound to A beta, but NACP delta, a deletion
      mutant of NACP lacking the NAC domain, did not bind A beta 1-38. Furthermore,
      binding between NACP-112 and A beta 1-38 was decreased by addition of peptide Y,
      a peptide that covers the last 15 residues of NAC. In an aqueous solution, A beta
      1-38 aggregation was observed when NACP was also present in an incubation mixture
      at a ratio of 1:125 (NACP/A beta), whereas A beta 1-38 alone or NACP alone did
      not aggregate under the same conditions, suggesting that the formation of a
      complex between A beta and NACP may promote aggregation of A beta. Thus, NACP can
      bind A beta peptides through the specific sequence and can promote A beta
      aggregation, raising the possibility that NACP may play a role in the development
      of AD amyloid.

PMID- 7568088
TI  - Selective vulnerability of late-generated dopaminergic neurons of the substantia
      nigra in weaver mutant mice.
AB  - In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic
      substantia nigra neurons degenerate by postnatal day 20. We have now determined
      that the total number of dopaminergic neurons in the ventral midbrains of a
      litter of obligatory homozygous weaver pups and a litter of normal wild-type
      control pups indicates that no significant differences are present between groups
      at birth. To test the hypothesis that the subsequent degeneration of these
      neurons is linked to their time of origin, [3H]thymidine autoradiography was
      combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic
      timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both
      groups have the same span of neurogenesis but have statistically different
      proportions of neurons generated on specific days. In wild-type mice, more than
      half of the dopaminergic neurons originate on or after embryonic day 12. In
      contrast, over two-thirds of the surviving dopaminergic neurons in homozygous
      weaver mice originate on or before embryonic day 11. Our data suggest that the
      weaver gene does not interfere with the generation of dopaminergic neurons, but
      it preferentially kills late-generated dopaminergic neurons between birth and
      postnatal day 20.

PMID- 7568087
TI  - Fungal metabolic model for human type I hereditary tyrosinaemia.
AB  - Type I hereditary tyrosinaemia (HT1) is a severe human inborn disease resulting
      from loss of fumaryl-acetoacetate hydrolase (Fah). Homozygous disruption of the
      gene encoding Fah in mice causes neonatal lethality, seriously limiting use of
      this animal as a model. We report here that fahA, the gene encoding Fah in the
      fungus Aspergillus nidulans, encodes a polypeptide showing 47.1% identity to its
      human homologue, fahA disruption results in secretion of succinylacetone (a
      diagnostic compound for human type I tyrosinaemia) and phenylalanine toxicity. We
      have isolated spontaneous suppressor mutations preventing this toxicity,
      presumably representing loss-of-function mutations in genes acting upstream of
      fahA in the phenylalanine catabolic pathway. Analysis of a class of these
      mutations demonstrates that loss of homogentisate dioxygenase (leading to
      alkaptonuria in humans) prevents the effects of a Fah deficiency. Our results
      strongly suggest human homogentisate dioxygenase as a target for HT1 therapy and
      illustrate the usefulness of this fungus as an alternative to animal models for
      certain aspects of human metabolic diseases.

PMID- 7568090
TI  - Efficient screening of retroviral cDNA expression libraries.
AB  - Expression cloning of cDNAs was first described a decade ago and was based on
      transient expression of cDNA libraries in COS cells. In contrast to transient
      transfection of plasmids, retroviral gene transfer delivers genes stably into a
      wide range of target cells. We utilize a simple packaging system for production
      of high-titer retrovirus stock from cDNA libraries to establish a cDNA expression
      cloning system. In two model experiments, murine interleukin (IL)-3-dependent
      Ba/F3 cells were infected with libraries of retrovirally expressed cDNA derived
      from human T-cell mRNA or human IL-3-dependent TF-1 cell line mRNA. These
      infected Ba/F3 cells were selected for the expression of CD2 by flow cytometry or
      for the alpha subunit of the human IL-3 receptor (hIL-3R alpha) by factor
      dependent growth. CD2 (frequency, 1 in 10(4)) and hIL-3R alpha (frequency, 1 in
      1.5 x 10(5)) cDNAs were readily detected in small-scale experiments, indicating
      this retroviral expression cloning system is efficient enough to clone low
      abundance cDNAs by their expression or function.

PMID- 7568091
TI  - Evidence for the presence of a protease-activated receptor distinct from the
      thrombin receptor in human keratinocytes.
AB  - Thrombin receptor activation was explored in human epidermal keratinocytes and
      human dermal fibroblasts, cells that are actively involved in skin tissue repair.
      The effects of thrombin, trypsin, and the receptor agonist peptides SFLLRN and
      TFRIFD were assessed in inositolphospholipid hydrolysis and calcium mobilization
      studies. Thrombin and SFLLRN stimulated fibroblasts in both assays to a similar
      extent, whereas TFRIFD was less potent. Trypsin demonstrated weak efficacy in
      these assays in comparison with thrombin. Results in fibroblasts were consistent
      with human platelet thrombin receptor activation. Keratinocytes, however,
      exhibited a distinct profile, with trypsin being a far better activator of
      inositolphospholipid hydrolysis and calcium mobilization than thrombin.
      Furthermore, SFLLRN was more efficacious than thrombin, whereas no response was
      observed with TFRIFD. Since our data indicated that keratinocytes possess a
      trypsin-sensitive receptor, we addressed the possibility that these cells express
      the human homologue of the newly described murine protease-activated receptor,
      PAR-2 [Nystedt, S., Emilsson, K., Wahlestedt, C. & Sundelin, J. (1994) Proc.
      Natl. Acad. Sci. USA 91, 9208-9212]. PAR-2 is activated by nanomolar
      concentrations of trypsin and possesses the tethered ligand sequence SLIGRL.
      SLIGRL was found to be equipotent with SFLLRN in activating keratinocyte
      inositolphospholipid hydrolysis and calcium mobilization. Desensitization studies
      indicated that SFLLRN, SLIGRL, and trypsin activate a common receptor, PAR-2.
      Northern blot analyses detected a transcript of PAR-2 in total RNA from
      keratinocytes but not fibroblasts. Levels of thrombin receptor message were
      equivalent in the two cell types. Our results indicate that human keratinocytes
      possess PAR-2, suggesting a potential role for this receptor in tissue repair
      and/or skin-related disorders.

PMID- 7568092
TI  - Protein kinase C chimeras: catalytic domains of alpha and beta II protein kinase
      C contain determinants for isotype-specific function.
AB  - Protein kinase C (PKC) is involved in the proliferation and differentiation of
      many cell types. In human erythroleukemia (K-562) cells, the PKC isoforms alpha
      and beta II play distinct functional roles. alpha PKC is involved in phorbol 12
      myristate 13-acetate-induced cytostasis and megakaryocytic differentiation,
      whereas beta II PKC is required for proliferation. To identify regions within
      alpha and beta II PKC that allow participation in these divergent pathways, we
      constructed chimeras in which the regulatory and catalytic domains of alpha and
      beta II PKC were exchanged. These PKC chimeras can be stably expressed, exhibit
      enzymatic properties similar to native alpha and beta II PKC in vitro, and
      participate in alpha and beta II PKC isotype-specific pathways in K-562 cells.
      Expression of the beta/alpha PKC chimera induces cytostasis in the same manner as
      overexpression of wild-type alpha PKC. In contrast, the alpha/beta II PKC
      chimera, like wild-type beta II PKC, selectively translocates to the nucleus and
      leads to increased phosphorylation of the nuclear envelope polypeptide lamin B in
      response to bryostatin-1. Therefore, the catalytic domains of alpha and beta II
      PKC contain determinants important for alpha and beta II PKC isotype function.
      These results suggest that the catalytic domain represents a potential target for
      modulating PKC isotype activity in vivo.

PMID- 7568093
TI  - Targeted disruption of vinculin genes in F9 and embryonic stem cells changes cell
      morphology, adhesion, and locomotion.
AB  - Vinculin, a major constituent of focal adhesions and zonula adherens junctions,
      is thought to be involved in linking the microfilaments to areas of cell
      substrate and cell-cell contacts. To test the role of vinculin in cell adhesion
      and motility, we used homologous recombination to generate F9 embryonal carcinoma
      and embryonic stem cell clones homozygous for a disrupted vinculin gene. When
      compared to wild-type cells, vinculin-mutant cells displayed a rounder morphology
      and a reduced ability to adhere and spread on plastic or fibronectin. Decreased
      adhesion of the mutant cells was associated with a reduction in lamellipodial
      extensions, as observed by time-lapse video microscopy. The locomotive activities
      of control F9 and the vinculin-null cells were compared in two assays. Loss of
      vinculin resulted in a 2.4-fold increase in cell motility. These results
      demonstrate an important role for vinculin in determining cell shape, adhesion,
      surface protrusive activity, and cell locomotion.

PMID- 7568095
TI  - Geographical structuring in the mtDNA of Italians.
AB  - Geographical patterns of mtDNA variation were studied in 12 Italian samples (1072
      individuals) by two different spatial autocorrelation methods. Separate analyses
      of the frequencies of 12 restriction morphs show North-South clines, differences
      between Sardinia and the mainland populations, and the effects of isolation by
      distance. A recently developed autocorrelation statistic summarizing molecular
      similarity at all sites (AIDA; autocorrelation index for DNA analysis) confirms
      the presence of a clinical pattern; differences between random pairs of
      haplotypes tend to increase with their geographical distance. The partition of
      gene diversity, however, reveals that most variability occurs within populations,
      whereas differences between populations are minor (GST = 0.057). When the data
      from the 12 samples are pooled, two descriptors of genetic variability (number of
      polymorphic sites and average sequence difference between pairs of individuals)
      do not behave as expected under neutrality. The presence of clinal patterns,
      Tajima's tests, and a simulation experiment agree in suggesting that population
      sizes increased rapidly in Italy and Sicily but not necessarily so in Sardinia.
      The distribution of pairwise sequence differences in the Italian peninsula
      (excluding Sardinia) permits a tentative location of the demographic increase
      between 8000 and 20,500 years ago. These dates are consistent with archaeological
      estimates of two distinct expansion processes, occurring, respectively, in the
      Neolithic and after the last glacial maximum in the Paleolithic. Conversely,
      there is no genetic evidence that such processes have had a major impact on the
      Sardinian population.

PMID- 7568094
TI  - The hexapeptide LFPWMR in Hoxb-8 is required for cooperative DNA binding with
      Pbx1 and Pbx2 proteins.
AB  - The Hox gene products are DNA-binding proteins, containing a homeodomain, which
      function as a class of master control proteins establishing the body plan in
      organisms as diverse as Drosophila and vertebrates. Hox proteins have recently
      been shown to bind cooperatively to DNA with another class of homeodomain
      proteins that include extradenticle, Pbx1, and Pbx2. Hox gene products contain a
      highly conserved hexapeptide connected by a linker of variable length to the
      homeodomain. We show that the hexapeptide and the linker region are required for
      cooperativity with Pbx1 and Pbx2 proteins. Many of the conserved residues present
      in the Hoxb-8 hexapeptide are required to modulate the DNA binding of the Pbx
      proteins. Position of the hexapeptide relative to the homeodomain is important.
      Although deletions of two and four residues of the linker peptide still show
      cooperative DNA binding, removal of all six linker residues strongly reduces
      cooperativity. In addition, an insertion of 10 residues within the linker peptide
      significantly lowers cooperative DNA binding. These results show that the
      hexapeptide and the position of the hexapeptide relative to the homeodomain are
      important determinants to allow cooperative DNA binding involving Hox and Pbx
      gene products.

PMID- 7568097
TI  - Sphingolipid synthesis as a target for chemotherapy against malaria parasites.
AB  - The human malaria parasite Plasmodium falciparum contains sphingomyelin synthase
      in its Golgi apparatus and in a network of tubovesicular membranes in the
      cytoplasm of the infected erythrocyte. Palmitoyl and decanoyl analogues of 1
      phenyl-2-acylamino-3-morpholino-1-propanol inhibit the enzyme activity in
      infected erythrocytes. An average of 35% of the activity is extremely sensitive
      to these drugs and undergoes a rapid, linear decrease at drug concentrations of
      0.05-1 microM. The remaining 65% suffers a slower linear inhibition at drug
      concentrations ranging from 25 to 500 microM. Evidence is presented that
      inhibition of the sensitive fraction alone selectively disrupts the appearance of
      the interconnected tubular network in the host cell cytoplasm, without blocking
      secretory development at the parasite plasma membrane or in organelles within the
      parasite, such as the Golgi and the digestive food vacuole. This inhibition also
      blocks parasite proliferation in culture, indicating that the sensitive
      sphingomyelin synthase activity as well as the tubovesicular network may provide
      rational targets for drugs against malaria.

PMID- 7568096
TI  - Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the
      tumor of a patient with cancer-associated retinopathy.
AB  - Recoverin is a member of the EF-hand family of calcium-binding proteins involved
      in the transduction of light by vertebrate photoreceptors. Recoverin also was
      identified as an autoantigen in the degenerative disease of the retina known as
      cancer-associated retinopathy (CAR), a paraneoplastic syndrome whereby
      immunological events lead to the degeneration of photoreceptors in some
      individuals with cancer. In this study, we demonstrate that recoverin is
      expressed in the lung tumor of a CAR patient but not in similar tumors obtained
      from individuals without the associated retinopathy. Recoverin was identified
      intially by Western blot analysis of the CAR patient's biopsy tissue by using
      anti-recoverin antibodies generated against different regions of the recoverin
      molecule. In addition, cultured cells from the biopsy tissue expressed recoverin,
      as demonstrated by reverse transcription-PCR using RNA extracted from the cells.
      The immunodominant region of recoverin also was determined in this study by a
      solid-phase immunoassay employing overlapping heptapeptides encompassing the
      entire recoverin sequence. Two linear stretches of amino acids (residues 64-70,
      Lys-Ala-Tyr-Ala-Gln-His-Val; and 48-52, Gln-Phe-Gln-Ser-Ile) made up the major
      determinants. One of the same regions of the recoverin molecule (residues 64-70)
      also was uniquely immunopathogenic, causing photoreceptor degeneration upon
      immunization of Lewis rats with the corresponding peptide. These data demonstrate
      that the neural antigen recoverin more than likely is responsible for the
      immunological events associated with vision loss in some patients with cancer.
      These data also establish CAR as one of the few autoimmune-mediated diseases for
      which the specific self-antigen is known.

PMID- 7568098
TI  - Helix packing of lactose permease in Escherichia coli studied by site-directed
      chemical cleavage.
AB  - Biotinylated lactose permease from Escherichia coli containing a single-cysteine
      residue at position 330 (helix X) or at position 147, 148, or 149 (helix V) was
      purified by avidin-affinity chromatography and derivatized with 5-(alpha
      bromoacetamido)-1,10-phenanthroline-copper [OP(Cu)]. Studies with purified,
      OP(Cu)-labeled Leu-330 --> Cys permease in dodecyl-beta-D-maltopyranoside
      demonstrate that after incubation in the presence of ascorbate, cleavage products
      of approximately 19 and 6-8 kDa are observed on immunoblots with anti-C-terminal
      antibody. Remarkably, the same cleavage products are observed with permease
      embedded in the native membrane. Comparison with the C-terminal half of the
      permease expressed independently as a standard indicates that the 19-kDa product
      results from cleavage near the cytoplasmic end of helix VII, whereas the 6- to 8
      kDa fragment probably results from fragmentation near the cytoplasmic end of
      helix XI. Results are entirely consistent with a tertiary-structure model of the
      C-terminal half of the permease derived from earlier site-directed fluorescence
      and site-directed mutagenesis studies. Similar studies with OP(Cu)-labeled Cys
      148 permease exhibit cleavage products at approximately 19 kDa and at 15-16 kDa.
      The larger fragment probably reflects cleavage at a site near the cytoplasmic end
      of helix VII, whereas the 15- to 16-kDa fragment is consistent with cleavage near
      the cytoplasmic end of helix VIII. When OP(Cu) is moved 100 degrees to position
      149 (Val-149 --> Cys permease), a single product is observed at 19 kDa,
      suggesting fragmentation at the cytoplasmic end of helix VII. However, when the
      reagent is moved 100 degrees in the other direction to position 147 (Gly-147 -->
      Cys permease), cleavage is not observed. The results suggest that helix V is in
      close proximity to helices VII and VIII with position 148 in the interface
      between the helices, position 149 facing helix VII, and position 147 facing the
      lipid bilayer.

PMID- 7568099
TI  - Down syndrome-critical region contains a gene homologous to Drosophila sim
      expressed during rat and human central nervous system development.
AB  - Many features of Down syndrome might result from the overdosage of only a few
      genes located in a critical region of chromosome 21. To search for these genes,
      cosmids mapping in this region were isolated and used for trapping exons. One of
      the trapped exons obtained has a sequence very similar to part of the Drosophila
      single-minded (sim) gene, a master regulator of the early development of the fly
      central nervous system midline. Mapping data indicated that this exonic sequence
      is only present in the Down syndrome-critical region in the human genome.
      Hybridization of this exonic sequence with human fetal kidney poly(A)+ RNA
      revealed two transcripts of 6 and 4.3 kb. In situ hybridization of a probe
      derived from this exon with human and rat fetuses showed that the corresponding
      gene is expressed during early fetal life in the central nervous system and in
      other tissues, including the facial, skull, palate, and vertebra primordia. The
      expression pattern of this gene suggests that it might be involved in the
      pathogenesis of some of the morphological features and brain anomalies observed
      in Down syndrome.

PMID- 7568101
TI  - Fc epsilon RI-mediated recruitment of p53/56lyn to detergent-resistant membrane
      domains accompanies cellular signaling.
AB  - Detergent-resistant plasma membrane structures, such as caveolae, have been
      implicated in signalling, transport, and vesicle trafficking functions. Using
      sucrose gradient ultracentrifugation, we have isolated low-density, Triton X-100
      insoluble membrane domains from RBL-2H3 mucosal mast cells that contain several
      markers common to caveolae, including a src-family tyrosine kinase, p53/56lyn.
      Aggregation of Fc epsilon RI, the high-affinity IgE receptor, causes a
      significant increase in the amount of p53/56lyn associated with these low-density
      membrane domains. Under our standard conditions for lysis, IgE-Fc epsilon RI
      fractionates with the majority of the solubilized proteins, whereas aggregated
      receptor complexes are found at a higher density in the gradient. Stimulated
      translocation of p53/56lyn is accompanied by increased tyrosine phosphorylation
      of several proteins in the low-density membrane domains as well as enhanced in
      vitro tyrosine kinase activity toward these proteins and an exogenous substrate.
      With a lower detergent-to-cell ratio during lysis, significant Fc epsilon RI
      remains associated with these membrane domains, consistent with the ability to
      coimmunoprecipitate tyrosine kinase activity with Fc epsilon RI under similar
      lysis conditions [Pribluda, V. S., Pribluda, C. & Metzger, H. (1994) Proc. Natl.
      Acad. Sci. USA 91, 11246-11250]. These results indicate that specialized membrane
      domains may be directly involved in the coupling of receptor aggregation to the
      activation of signaling events.

PMID- 7568100
TI  - Association of the "major histocompatibility complex subregion" I-J determinant
      with bioactive glycosylation-inhibiting factor.
AB  - Murine suppressor T-cell hybridoma cells (231F1) secrete not only bioactive
      glycosylation-inhibiting factor (GIF) but also an inactive peptide comparable to
      bioactive GIF peptide in its molecular size and reactivity with anti-GIF; the
      amino acid sequence of the inactive peptide is identical to that of the bioactive
      homologue. The inactive GIF peptide in culture supernatant of both the 231F1
      cells and a stable transfectant of human GIF cDNA in the murine suppressor T
      hybridoma selectively bound to Affi-Gel 10, whereas bioactive GIF peptides from
      the same sources failed to bind to the gel. The inactive cytosolic human GIF from
      the stable transfectant and Escherichia coli-derived recombinant human GIF also
      had affinity for Affi-Gel 10. Both the bioactive murine GIF peptide from the
      suppressor T hybridoma and bioactive recombinant human GIF from the stable
      transfectant bound to the anti-I-J monoclonal antibody H6 coupled to Affi-Gel.
      However, bioactive hGIF produced by a stable transfectant of human GIF cDNA in
      BMT10 cells failed to be retained in H6-coupled Affi-Gel. These results indicate
      that the I-J specificity is determined by the cell source of the GIF peptide and
      that the I-J determinant recognized by monoclonal antibody H6 does not represent
      a part of the primary amino acid sequence of GIF. It appears that the epitope is
      generated by a posttranslational modification of the peptide.

PMID- 7568102
TI  - Lattice model for rapidly folding protein-like heteropolymers.
AB  - Protein folding is a relatively fast process considering the astronomical number
      of conformations in which a protein could find itself. Within the framework of a
      lattice model, we show that one can design rapidly folding sequences by assigning
      the strongest attractive couplings to the contacts present in a target native
      state. Our protein design can be extended to situations with both attractive and
      repulsive contacts. Frustration is minimized by ensuring that all the native
      contacts are again strongly attractive. Strikingly, this ensures the
      inevitability of folding and accelerates the folding process by an order of
      magnitude. The evolutionary implications of our findings are discussed.

PMID- 7568103
TI  - Mixing of connexins in gap junction membrane channels.
AB  - Gap junctions are plaque-like clusters of intercellular channels that mediate
      intercellular communication. Each of two adjoining cells contains a connexon unit
      which makes up half of the whole channel. Gap junction channels are formed from a
      multigene family of proteins called connexins, and different connexins may be
      coexpressed by a single cell type and found within the same plaque. Rodent gap
      junctions contain two proteins, connexins 32 and 26. Use of a scanning
      transmission electron microscope for mass analysis of rodent gap junction plaques
      and split gap junctions prvided evidence consistent with a model in which the
      channels may be made from (i) solely connexin 26, (ii) solely connexin 32, or
      (iii) mixtures of connexin 26 and connexin 32 in which the two connexons are made
      entirely of connexin 26 and connexin 32. The different types of channels
      segregate into distinct domains, implying tha connexon channels self-associate to
      give a non-random distribution within tissues. Since each connexin confers
      distinct physiological properties on its membrane channels, these results imply
      that the physiological properties of channels can be tailored by mixing the
      constituent proteins within these macromolecular structures.

PMID- 7568104
TI  - A structural motif for the voltage-gated potassium channel pore.
AB  - Mutation studies have identified a region of the S5-S6 loop of voltage-gated K+
      channels (P region) responsible for teraethylammonium (TEA) block and
      permeation/selectivity properties. We previously modeled a similar region of the
      Na+ channel as four beta-hairpins with the C strands from each of the domains
      forming the external vestibule and with charged residues at the beta-turns
      forming the selectivity filter. However, the K+ channel P region amino acid
      composition is much more hydrophobic in this area. Here we propose a structural
      motif for the K+ channel pore based on the following postulates (Kv2.1
      numbering). (i) The external TEA binding site is formed by four Tyr-380 residues;
      P loop residues participating in the internal TEA binding site are four Met-371
      and Thr-372 residues. (ii) P regions form extended hairpins with beta-turns in
      sequence ITMT. (iii) only C ends of hairpins form the inner walls of the pore.
      (iv) They are extended nonregular strands with backbone carbonyl oxygens of
      segment VGYGD facing the pore with the conformation BRLRL. (v) Juxtaposition of P
      loops of the four subunits forms the pore. Fitting the external and internal TEA
      sites to TEA molecules predicts an hourglass-like pore with the narrowest point
      (GYG) as wide as 5.5 A, suggesting that selectivity may be achieved by
      interactions of carbonyls with partially hydrated K+. Other potential cation
      binding sites also exist in the pore.

PMID- 7568105
TI  - 4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes:
      implications for the mechanism of uterine tumorigenesis.
AB  - Estradiol is converted to catechol estrogens via 2- and 4-hydroxylation by
      cytochrome P450 enzymes. 4-Hydroxyestradiol elicits biological activities
      distinct from estradiol, most notably an oxidant stress response induced by free
      radicals generated by metabolic redox cycling reactions. In this study, we have
      examined 2- and 4-hydroxylation of estradiol by microsomes of human uterine
      myometrium and of associated myomata. In all eight cases studied, estradiol 4
      hydroxylation by myoma has been substantially elevated relative to surrounding
      myometrial tissue (minimum, 2-fold; mean, 5-fold). Estradiol 2-hydroxylation in
      myomata occurs at much lower rates than 4-hydroxylation (ratio of 4
      hydroxyestradiol/2-hydroxyestradiol, 7.9 +/- 1.4) and does not significantly
      differ from rates in surrounding myometrial tissue. Rates of myometrial 2
      hydroxylation of estradiol were also not significantly different from values in
      patients without myomata. We have used various inhibitors to establish that 4
      hydroxylation is catalyzed by a completely different cytochrome P450 than 2
      hydroxylation. In myoma, alpha-naphthoflavone and a set of ethynyl polycyclic
      hydrocarbon inhibitors (5 microM) each inhibited 4-hydroxylation more efficiently
      (up to 90%) than 2-hydroxylation (up to 40%), indicating > 10-fold differences in
      Ki (<0.5 microM vs. > 5 microM). These activities were clearly distinguished from
      the selective 2-hydroxylation of estradiol in placenta by aromatase reported
      previously (low Km, inhibition by Fadrozole hydrochloride or ICI D1033). 4
      Hydroxylation was also selectively inhibited relative to 2-hydroxylation by
      antibodies raised against cytochrome P450 IB1 (rat) (53 vs. 17%). These data
      indicate that specific 4-hydroxylation of estradiol in human uterine tissues is
      catalyzed by a form(s) of cytochrome P450 related to P450 IB1, which
      contribute(s) little to 2-hydroxylation. This enzyme(s) is therefore a marker for
      uterine myomata and may play a role in the etiology of the tumor.

PMID- 7568106
TI  - Suppression of synapsin II inhibits the formation and maintenance of synapses in
      hippocampal culture.
AB  - Numerous synaptic proteins, including several integral membrane proteins, have
      been assigned roles in synaptic vesicle fusion with or retrieval from the
      presynaptic plasma membrane. In contrast, the synapsins, neuron-specific
      phosphoproteins associated with the cytoplasmic surface of synaptic vesicles,
      appear to play a much broader role, being involved in the regulation of
      neurotransmitter release and in the organization of the nerve terminal. Here we
      have administered antisense synapsin II oligonucleotides to dissociated
      hippocampal neurons, either before the onset of synaptogenesis or 1 week after
      the onset of synaptogenesis. In both cases, synapsin II was no longer detectable
      within 24-48 h of treatment. After 5 days of treatment, cultures were analyzed
      for the presence of synapses by synapsin I and synaptophysin antibody labeling
      and by electron microscopy. Cultures in which synapsin II was suppressed after
      axon elongation, but before synapse formation, did not develop synapses. Cultures
      in which synapsin II was suppressed after the development of synapses lost most
      of their synapses. Remarkably, with the removal of the antisense
      oligonucleotides, neurons and their synaptic connections recovered. These studies
      lead us to conclude that synapsin II is involved in the formation and maintenance
      of synapses in hippocampal neurons.

PMID- 7568107
TI  - Impairment of axonal development and of synaptogenesis in hippocampal neurons of
      synapsin I-deficient mice.
AB  - Synapsin I, the most abundant of all neuronal phosphoproteins, is enriched in
      synaptic vesicles. It has been hypothesized to regulate synaptogenesis and
      neurotransmitter release from adult nerve terminals. The evidence for such roles
      has been highly suggestive but not compelling. To evaluate the possible
      involvement of synapsin I in synaptogenesis and in the function of adult
      synapses, we have generated synapsin I-deficient mice by homologous
      recombination. We report herein that outgrowth of predendritic neurites and of
      axons was severely retarded in the hippocampal neurons of embryonic synapsin I
      mutant mice. Furthermore, synapse formation was significantly delayed in these
      mutant neurons. These results indicate that synapsin I plays a role in regulation
      of axonogenesis and synaptogenesis.

PMID- 7568108
TI  - Impairment of synaptic vesicle clustering and of synaptic transmission, and
      increased seizure propensity, in synapsin I-deficient mice.
AB  - Synapsin I has been proposed to be involved in the modulation of neurotransmitter
      release by controlling the availability of synaptic vesicles for exocytosis. To
      further understand the role of synapsin I in the function of adult nerve
      terminals, we studied synapsin I-deficient mice generated by homologous
      recombination. The organization of synaptic vesicles at presynaptic terminals of
      synapsin I-deficient mice was markedly altered: densely packed vesicles were only
      present in a narrow rim at active zones, whereas the majority of vesicles were
      dispersed throughout the terminal area. This was in contrast to the organized
      vesicle clusters present in terminals of wild-type animals. Release of glutamate
      from nerve endings, induced by K+,4-aminopyridine, or a Ca2+ ionophore, was
      markedly decreased in synapsin I mutant mice. The recovery of synaptic
      transmission after depletion of neurotransmitter by high-frequency stimulation
      was greatly delayed. Finally, synapsin I-deficient mice exhibited a strikingly
      increased response to electrical stimulation, as measured by electrographic and
      behavioral seizures. These results provide strong support for the hypothesis that
      synapsin I plays a key role in the regulation of nerve terminal function in
      mature synapses.

PMID- 7568109
TI  - Genetic transfer of a nonpeptide antagonist binding site to a previously
      unresponsive angiotensin receptor.
AB  - Mutational analysis based on the pharmacological differences between mammalian
      and amphibian angiotensin II receptors (AT receptors) previously identified 7 aa
      residues located in transmembrane domains (TMs) III (Val-108), IV (Ala-163), V
      (Pro-192, Thr-198), VI (Ser-252), and VII (Leu-300, Phe-301) of the rat AT
      receptor type 1b (rAT1b receptor) that significantly influenced binding of the
      nonpeptide antagonist Losartan. Further studies have shown that an additional 6
      residues in the rAT1b receptor TMs II (Ala-73), III (Ser-109, Ala-114, Ser-115),
      VI (Phe-248), and VII (Asn-295) are important in Losartan binding. The 13
      residues required for Losartan binding in the mammalian receptor were exchanged
      for the corresponding amino acids in the Xenopus AT receptor type a (xATa
      receptor) to generate a mutant amphibian receptor that bound Losartan with the
      same affinity as the rAT1b receptor (Losartan IC50 values: rAT1b, 2.2 +/- 0.2 nM:
      xATa, > 50 microM; mutant, 2.0 +/- 0.1 nM). To our knowledge, this is the first
      report of a gain-of-function mutant in which the residues crucial to formation of
      a ligand binding site in a mammalian peptide hormone receptor were transferred to
      a previously unresponsive receptor by site-directed mutagenesis. Ala
      substitutions and comparison of mammalian and amphibian combinatorial mutants
      indicated that TM III in the rAT1b receptor plays a key role in Losartan binding.
      Identification of residues involved in nonpeptide ligand binding will facilitate
      studies aimed at elucidating the chemical basis for ligand recognition in the AT
      receptor and peptide hormone receptors in general.

PMID- 7568110
TI  - Molecular cloning and sequence analysis of expansins--a highly conserved,
      multigene family of proteins that mediate cell wall extension in plants.
AB  - Expansins are unusual proteins discovered by virtue of their ability to mediate
      cell wall extension in plants. We identified cDNA clones for two cucumber
      expansins on the basis of peptide sequences of proteins purified from cucumber
      hypocotyls. The expansin cDNAs encode related proteins with signal peptides
      predicted to direct protein secretion to the cell wall. Northern blot analysis
      showed moderate transcript abundance in the growing region of the hypocotyl and
      no detectable transcripts in the nongrowing region. Rice and Arabidopsis expansin
      cDNAs were identified from collections of anonymous cDNAs (expressed sequence
      tags). Sequence comparisons indicate at least four distinct expansin cDNAs in
      rice and at least six in Arabidopsis. Expansins are highly conserved in size and
      sequence (60-87% amino acid sequence identity and 75-95% similarity between any
      pairwise comparison), and phylogenetic trees indicate that this multigene family
      formed before the evolutionary divergence of monocotyledons and dicotyledons.
      Sequence and motif analyses show no similarities to known functional domains that
      might account for expansin action on wall extension. A series of highly conserved
      tryptophans may function in expansin binding to cellulose or other glycans. The
      high conservation of this multigene family indicates that the mechanism by which
      expansins promote wall extensin tolerates little variation in protein structure.

PMID- 7568111
TI  - A nonpeptide agonist of the invertebrate receptor for SchistoFLRFamide
      (PDVDHVFLRFamide), a member of a subfamily of insect FMRFamide-related peptides.
AB  - We describe a nonpeptide mimetic analog of an invertebrate peptide receptor.
      Benzethonium chloride (Bztc) is an agonist of the SchistoFLRFamide
      (PDVDHVFLRFamide) receptors found on locust oviducts. Bztc competitively
      displaces [125I-labeled Y1]SchistoFLRFamide binding to both high- and low
      affinity receptors of membrane preparations. Bztc mimics the physiological
      effects of SchistoFLRFamide on locust oviduct, by inhibiting myogenic and induced
      contractions in a dose-dependent manner. Bztc is therefore recognized by the
      binding and activation regions of the SchistoFLRFamide receptors. This discovery
      provides a unique opportunity within insects to finally target a peptide receptor
      for the development of future pest management strategies.

PMID- 7568112
TI  - The anchorage function of CipA (CelL), a scaffolding protein of the Clostridium
      thermocellum cellulosome.
AB  - Enzymatic cellulose degradation is a heterogeneous reaction requiring binding of
      soluble cellulase molecules to the solid substrate. Based on our studies of the
      cellulase complex of Clostridium thermocellum (the cellulosome), we have
      previously proposed that such binding can be brought about by a special
      "anchorage subunit." In this "anchor-enzyme" model, CipA (a major subunit of the
      cellulosome) enhances the activity of CelS (the most abundant catalytic subunit
      of the cellulosome) by anchoring it to the cellulose surface. We have
      subsequently reported that CelS contains a conserved duplicated sequence at its C
      terminus and that CipA contains nine repeated sequences with a cellulose binding
      domain (CBD) in between the second and third repeats. In this work, we reexamined
      the anchor-enzyme mechanism by using recombinant CelS (rCelS) and various CipA
      domains, CBD, R3 (the repeat next to CBD), and CBD/R3, expressed in Escherichia
      coli. As analyzed by non-denaturing gel electrophoresis, rCelS, through its
      conserved duplicated sequence, formed a stable complex with R3 or CBD/R3 but not
      with CBD. Although R3 or CBD alone did not affect the binding of rCelS to
      cellulose, such binding was dependent on CBD/R3, indicating the anchorage role of
      CBD/R3. Such anchorage apparently increased the rCelS activity toward crystalline
      cellulose. These results substantiate the proposed anchor-enzyme model and the
      expected roles of individual CipA domains and the conserved duplicated sequence
      of CelS.

PMID- 7568114
TI  - Crystal structure of the large fragment of Thermus aquaticus DNA polymerase I at
      2.5-A resolution: structural basis for thermostability.
AB  - The crystal structure of the large fragment of the Thermus aquaticus DNA
      polymerase (Klentaq1), determined at 2.5-A resolution, demonstrates a compact two
      domain architecture. The C-terminal domain is identical in fold to the equivalent
      region of the Klenow fragment of Escherichia coli DNA polymerase I (Klenow pol
      I). Although the N-terminal domain of Klentaq1 differs greatly in sequence from
      its counterpart in Klenow pol I, it has clearly evolved from a common ancestor.
      The structure of Klentaq1 reveals the strategy utilized by this protein to
      maintain activity at high temperatures and provides the structural basis for
      future improvements of the enzyme.

PMID- 7568115
TI  - The site of action of neuronal acidic fibroblast growth factor is the organ of
      Corti of the rat cochlea.
AB  - Here we show that the mature cochlear neurons are a rich source of acidic
      fibroblast growth factor (aFGF), which is expressed in the neuronal circuitry
      consisting of afferent and efferent innervation. The site of action of neuronal
      aFGF is likely to reside in the organ of Corti, where one of the four known FGF
      receptor (FGFR) tyrosine kinases--namely, FGFR-3 mRNA--is expressed. Following
      acoustic overstimulation, known to cause damage to the organ of Corti, a rapid up
      regulation of FGFR-3 is evident in this sensory epithelium, at both mRNA and
      protein levels. The present results provide in vivo evidence for aFGF being a
      sensory neuron-derived, anterogradely transported factor that may exert trophic
      effects on a peripheral target tissue. In this sensory system, aFGF, rather than
      being a neurotrophic factor, seems to promote maintenance of the integrity of the
      organ of Corti. In addition, aFGF, released from the traumatized nerve endings,
      may be one of the first signals initiating protective recovery and repair
      processes following damaging auditory stimuli.

PMID- 7568113
TI  - Mouse model of human beta zero thalassemia: targeted deletion of the mouse beta
      maj- and beta min-globin genes in embryonic stem cells.
AB  - beta zero-Thalassemia is an inherited disorder characterized by the absence of
      beta-globin polypeptides derived from the affected allele. The molecular basis
      for this deficiency is a mutation of the adult beta-globin structural gene or cis
      regulatory elements that control beta-globin gene expression. A mouse model of
      this disease would enable the testing of therapeutic regimens designed to correct
      the defect. Here we report a 16-kb deletion that includes both adult beta-like
      globin genes, beta maj and beta min, in mouse embryonic stem cells. Heterozygous
      animals derived from the targeted cells are severely anemic with dramatically
      reduced hemoglobin levels, abnormal red cell morphology, splenomegaly, and
      markedly increased reticulocyte counts. Homozygous animals die in utero; however,
      heterozygous mice are fertile and transmit the deleted allele to progeny. The
      anemic phenotype is completely rescued in progeny derived from mating beta zero
      thalassemic animals with transgenic mice expressing high levels of human
      hemoglobin A. The beta zero-thalassemic mice can be used to test genetic
      therapies for beta zero-thalassemia and can be bred with transgenic mice
      expressing high levels of human hemoglobin HbS to produce an improved mouse model
      of sickle cell disease.

PMID- 7568117
TI  - Nuclear magnetic dipole interactions in field-oriented proteins: information for
      structure determination in solution.
AB  - The measurement of dipolar contributions to the splitting of 15N resonances of 1H
      15N amide pairs in multidimensional high-field NMR spectra of field-oriented
      cyanometmyoglobin is reported. The splittings appear as small field-dependent
      perturbations of normal scalar couplings. Assignment of more than 90 resonances
      to specific sequential sites in the protein allows correlation of the dipolar
      contributions with predictions based on the known susceptibility and known
      structure of the protein. Implications as an additional source of information for
      protein structure determination in solution are discussed.

PMID- 7568116
TI  - Molecular cloning, characterization, and functional expression of rat
      oxidosqualene cyclase cDNA.
AB  - A cDNA encoding rat oxidosqualene lanosterol-cyclase [lanosterol synthase; (S)
      2,3-epoxysqualene mutase (cyclizing, lanosterol-forming), EC 5.4.99.7] was cloned
      and sequenced by a combination of PCR amplification, using primers based on
      internal amino acid sequence of the purified enzyme, and cDNA library screening
      by oligonucleotide hybridization. An open reading frame of 2199 bp encodes a M(r)
      83,321 protein with 733 amino acids. The deduced amino acid sequence of the rat
      enzyme showed significant homology to the known oxidosqualene cyclases (OSCs)
      from yeast and plant (39-44% identity) and still retained 17-26% identity to two
      bacterial squalene cyclases (EC 5.4.99.-). Like other cyclases, the rat enzyme is
      rich in aromatic amino acids and contains five so-called QW motifs, highly
      conserved regions with a repetitive beta-strand turn motif. The binding site
      sequence for the 29-methylidene-2,3-oxidosqualene (29-MOS), a mechanism-based
      irreversible inhibitor specific for the vertebrate cyclase, is well-conserved in
      all known OSCs. The hydropathy plot revealed a rather hydrophilic N-terminal
      region and the absence of a hydrophobic signal peptide. Unexpectedly, this
      microsomal membrane-associated enzyme showed no clearly delineated transmembrane
      domain. A full-length cDNA was constructed and subcloned into a pYEUra3 plasmid,
      selected in Escherichia coli cells, and used to transform the OSC-deficient
      uracil-auxotrophic SGL9 strain of Saccharomyces cerevisiae. The recombinant rat
      OSC expressed was efficiently labeled by the mechanism-based inhibitor [3H]29
      MOS.

PMID- 7568118
TI  - G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.
AB  - The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis
      toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits
      of heterotrimeric G proteins (G beta gamma), p21ras activation, and an as-yet
      unidentified tyrosine kinase. To investigate the mechanism of G beta gamma
      stimulated p21ras activation, G beta gamma-mediated tyrosine phosphorylation was
      examined by overexpressing G beta gamma or alpha 2-C10 adrenergic receptors (ARs)
      that couple to Gi in COS-7 cells. Immunoprecipitation of phosphotyrosine
      containing proteins revealed a 2- to 3-fold increase in the phosphorylation of
      two proteins of approximately 50 kDa (designated as p52) in G beta gamma
      transfected cells or in alpha 2-C10 AR-transfected cells stimulated with the
      agonist UK-14304. The latter response was pertussis toxin sensitive. These
      proteins (p52) were also specifically immunoprecipitated with anti-Shc antibodies
      and comigrated with two Shc proteins, 46 and 52 kDa. The G beta gamma- or alpha 2
      C10 AR-stimulated p52 (Shc) phosphorylation was inhibited by coexpression of the
      carboxyl terminus of beta-adrenergic receptor kinase (a G beta gamma-binding
      pleckstrin homology domain peptide) or by the tyrosine kinase inhibitors
      genistein and herbimycin A, but not by a dominant negative mutant of p21ras.
      Worthmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K)
      inhibited phosphorylation of p52 (Shc), implying involvement of PI3K. These
      results suggest that G beta gamma-stimulated Shc phosphorylation represents an
      early step in the pathway leading to p21ras activation, similar to the mechanism
      utilized by growth factor tyrosine kinase receptors.

PMID- 7568120
TI  - Stimulation of mouse mammary tumor virus superantigen expression by an intragenic
      enhancer.
AB  - The mechanisms regulating expression of mouse mammary tumor virus (MMTV)-encoded
      superantigens from the viral sag gene are largely unknown, due to problems with
      detection and quantification of these low-abundance proteins. To study the
      expression and regulation of the MMTV sag gene, we have developed a sensitive and
      quantitative reporter gene assay based on a recombinant superantigen-human
      placental alkaline phosphatase fusion protein. High sag-reporter expression in
      Ba/F3, an early B-lymphoid cell line, depends on enhancers in either of the viral
      long terminal repeats (LTRs) and is largely independent of promoters in the 5'
      LTR. The same enhancer region is also required for general expression of MMTV
      genes from the 5' LTR. The enhancer was mapped to a 548-bp fragment of the MMTV
      LTR lying within sag and shown to be sufficient to stimulate expression from a
      heterologous simian virus 40 promoter. No enhancer activity of the MMTV LTR was
      observed in XC sarcoma cells, which are permissive for MMTV. Our results
      demonstrate a major role for this enhancer in MMTV gene expression in early B
      lymphoid cells.

PMID- 7568122
TI  - Reversible phosphorylation controls the activity of cyclosome-associated cyclin
      ubiquitin ligase.
AB  - Cyclin B/cdc2 is responsible both for driving cells into mitosis and for
      activating the ubiquitin-dependent degradation of mitotic cyclins near the end of
      mitosis, an event required for the completion of mitosis and entry into
      interphase of the next cell cycle. Previous work with cell-free extracts of
      rapidly dividing clam embryos has identified two specific components required for
      the ubiquitination of mitotic cyclins: E2-C, a cyclin-selective ubiquitin carrier
      protein that is constitutively active during the cell cycle, and E3-C, a cyclin
      selective ubiquitin ligase that purifies as part of a approximately 1500-kDa
      complex, termed the cyclosome, and which is active only near the end of mitosis.
      Here, we have separated the cyclosome from its ultimate upstream activator, cdc2.
      The mitotic, active form of the cyclosome can be inactivated by incubation with a
      partially purified, endogenous okadaic acid-sensitive phosphatase; addition of
      cdc2 restores activity to the cyclosome after a lag that reproduces that seen
      previously in intact cells and in crude extracts. These results demonstrate that
      activity of cyclin-ubiquitin ligase is controlled by reversible phosphorylation
      of the cyclosome complex.

PMID- 7568119
TI  - CD14 enhances cellular responses to endotoxin without imparting ligand-specific
      recognition.
AB  - Binding of the lipid A portion of bacterial lipopolysaccharide (LPS) to leukocyte
      CD14 activates phagocytes and initiates the septic shock syndrome. Two lipid A
      analogs, lipid IVA and Rhodobacter sphaeroides lipid A (RSLA), have been
      described as LPS-receptor antagonists when tested with human phagocytes. In
      contrast, lipid IVA activated murine phagocytes, whereas RSLA was an LPS
      antagonist. Thus, these compounds displayed a species-specific pharmacology. To
      determine whether the species specificity of these LPS antagonists occurred as a
      result of interactions with CD14, the effects of lipid IVA and RSLA were examined
      by using human, mouse, and hamster cell lines transfected with murine or human
      CD14 cDNA expression vectors. These transfectants displayed sensitivities to
      lipid IVA and RSLA that reflected the sensitivities of macrophages of similar
      genotype (species) and were independent of the source of CD14 cDNA. For example,
      hamster macrophages and hamster fibroblasts transfected with either mouse or
      human-derived CD14 cDNA responded to lipid IVA and RSLA as LPS mimetics.
      Similarly, lipid IVA and RSLA acted as LPS antagonists in human phagocytes and
      human fibrosarcoma cells transfected with either mouse or human-derived CD14
      cDNA. Therefore, the target of these LPS antagonists, which is encoded in the
      genomes of these cells, is distinct from CD14. Although the expression of CD14 is
      required for macrophage-like sensitivity to LPS, CD14 cannot discriminate between
      the lipid A moieties of these agents. We hypothesize that the target of the LPS
      antagonists is a lipid A recognition protein which functions as a signaling
      receptor that is triggered after interaction with CD14-bound LPS.

PMID- 7568121
TI  - Intracellular polyamines mediate inward rectification of Ca(2+)-permeable alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that
      lack the glutamate receptor GluR2 subunit are Ca(2+)-permeable and exhibit
      inwardly rectifying current responses to kainate and AMPA. A proportion of
      cultured rat hippocampal neurons show similar Ca(2+)-permeable inwardly
      rectifying AMPA receptor currents. Inward rectification in these neurons was lost
      with intracellular dialysis and was not present in excised outside-out patches
      but was maintained in perforated-patch whole-cell recordings, suggesting that a
      diffusible cytoplasmic factor may be responsible for rectification. Inclusion of
      the naturally occurring polyamines spermine and spermidine in the recording
      pipette prevented loss of rectification in both whole-cell and excised-patch
      recordings; Mg2+ and putrescine were without effect. Inward rectification of
      Ca(2+)-permeable AMPA receptors may reflect voltage-dependent channel block by
      intracellular polyamines.

PMID- 7568123
TI  - The crystal structure of Pseudomonas aeruginosa exotoxin domain III with
      nicotinamide and AMP: conformational differences with the intact exotoxin.
AB  - Domain III of Pseudomonas aeruginosa exotoxin A catalyses the transfer of ADP
      ribose from NAD to a modified histidine residue of elongation factor 2 in
      eukaryotic cells, thus inactivating elongation factor 2. This domain III is
      inactive in the intact toxin but is active in the isolated form. We report here
      the 2.5-A crystal structure of this isolated domain crystallized in the presence
      of NAD and compare it with the corresponding structure in the intact Pseudomonas
      aeruginosa exotoxin A. We observe a significant conformational difference in the
      active site region from Arg-458 to Asp-463. Contacts with part of domain II in
      the intact toxin prevent the adoption of the isolated domain conformation and
      provide a structural explanation for the observed inactivity. Additional electron
      density in the active site region corresponds to separate AMP and nicotinamide
      and indicates that the NAD has been hydrolyzed. The structure has been compared
      with the catalytic domain of the diphtheria toxin, which was crystallized with
      ApUp.

PMID- 7568125
TI  - Stopped-flow NMR spectroscopy: real-time unfolding studies of 6-19F-tryptophan
      labeled Escherichia coli dihydrofolate reductase.
AB  - Escherichia coli dihydrofolate reductase (DHFR; EC 1.5.1.3) contains five
      tryptophan residues that have been replaced with 6-19F-tryptophan. The 19F NMR
      assignments are known in the native, unliganded form and the unfolded form. We
      have used these assignments with stopped-flow 19F NMR spectroscopy to investigate
      the behavior of specific regions of the protein in real time during urea-induced
      unfolding. The NMR data show that within 1.5 sec most of the intensities of the
      native 19F resonances of the protein are lost but only a fraction (approximately
      20%) of the intensities of the unfolded resonances appears. We postulate that the
      early disappearance of the native resonances indicates that most of the protein
      rapidly forms an intermediate in which the side chains have considerable
      mobility. Stopped-flow far-UV circular dichroism measurements indicate that this
      intermediate retains native-like secondary structure. Eighty percent of the
      intensities of the NMR resonances assigned to the individual tryptophans in the
      unfolded state appear with similar rate constants (k approximately 0.14 sec-1),
      consistent with the major phase of unfolding observed by stopped-flow circular
      dichroism (representing 80% of total amplitude). These data imply that after
      formation of the intermediate, which appears to represent an expanded structural
      form, all regions of the protein unfold at the same rate. Stopped-flow
      measurements of the fluorescence and circular dichroism changes associated with
      the urea-induced unfolding show a fast phase (half-time of about 1 sec)
      representing 20% of the total amplitude in addition to the slow phase mentioned
      above. The NMR data show that approximately 20% of the total intensity for each
      of the unfolded tryptophan resonances is present at 1.5 sec, indicating that
      these two phases may represent the complete unfolding of the two different
      populations of the native protein.

PMID- 7568124
TI  - Gut-specific transcriptional regulatory elements of the carboxypeptidase gene are
      conserved between black flies and Drosophila.
AB  - Millions of people die every year in the tropical world from diseases transmitted
      by hematophagous insects. Failure of conventional containment measures emphasizes
      the need for additional approaches, such as transformation of vector insects with
      genes that restrict vectorial capacity. The availability of an efficient promoter
      to drive foreign genes in transgenic insects is a necessary tool to test the
      feasibility of such approach. Here we characterize the putative promoter region
      of a black fly midgut carboxypeptidase gene and show that these sequences
      correctly direct the expression of a beta-glucuronidase reporter in Drosophila
      melanogaster. By histochemical staining and mRNA analysis, we found that the gene
      is expressed strongly and gut-specifically in the transgenic Drosophila. This gut
      specific black fly carboxypeptidase promoter provides a valuable tool for the
      study of disease vectors.

PMID- 7568126
TI  - 12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid
      regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated
      hydrolysis of inositol phospholipids.
AB  - Protein kinase C (PKC) isoenzymes are essential components of cell signaling. In
      this study, we investigated the regulation of PKC-alpha in murine B16 amelanotic
      melanoma (B16a) cells by the monohydroxy fatty acids 12(S)
      hydroxyeicosatetraenoic acid [12(S)-HETE] and 13(S)-hydroxyoctadecadienoic acid
      [13(S)-HODE]. 12(S)-HETE induced a translocation of PKC-alpha to the plasma
      membrane and focal adhesion plaques, leading to enhanced adhesion of B16a cells
      to the matrix protein fibronectin. However, 13(S)-HODE inhibited these 12(S)-HETE
      effects on PKC-alpha. A receptor-mediated mechanism of action for 12(S)-HETE and
      13(S)-HODE is supported by the following findings. First, 12(S)-HETE triggered a
      rapid increase in cellular levels of diacylglycerol and inositol trisphosphate in
      B16a cells. 13(S)-HODE blocked the 12(S)-HETE-induced bursts of both second
      messengers. Second, the 12(S)-HETE-increased adhesion of B16a cells to
      fibronectin was sensitive to inhibition by a phospholipase C inhibitor and
      pertussis toxin. Finally, a high-affinity binding site (Kd = 1 nM) for 12(S)-HETE
      was detected in B16a cells, and binding of 12(S)-HETE to B16a cells was
      effectively inhibited by 13(S)-HODE (IC50 = 4 nM). In summary, our data provide
      evidence that regulation of PKC-alpha by 12(S)-HETE and 13(S)-HODE may be through
      a guanine nucleotide-binding protein-linked receptor-mediated hydrolysis of
      inositol phospholipids.

PMID- 7568127
TI  - Tumor necrosis factors alpha and beta protect neurons against amyloid beta
      peptide toxicity: evidence for involvement of a kappa B-binding factor and
      attenuation of peroxide and Ca2+ accumulation.
AB  - In Alzheimer disease (AD) the amyloid beta-peptide (A beta) accumulates in
      plaques in the brain. A beta can be neurotoxic by a mechanism involving induction
      of reactive oxygen species (ROS) and elevation of intracellular free calcium
      levels ([Ca2+]i). In light of evidence for an inflammatory response in the brain
      in AD and reports of increased levels of tumor necrosis factor (TNF) in AD brain
      we tested the hypothesis that TNFs affect neuronal vulnerability to A beta. A
      beta-(25-35) and A beta-(1-40) induced neuronal degeneration in a concentration-
      and time-dependent manner. Pretreatment of cultures for 24 hr with TNF-beta or
      TNF-alpha resulted in significant attenuation of A beta-induced neuronal
      degeneration. Accumulation of peroxides induced in neurons by A beta was
      significantly attenuated in TNF-pretreated cultures, and TNFs protected neurons
      against iron toxicity, suggesting that TNFs induce antioxidant pathways. The
      [Ca2+]i response to glutamate (quantified by fura-2 imaging) was markedly
      potentiated in neurons exposed to A beta, and this action of A beta was
      suppressed in cultures pretreated with TNFs. Electrophoretic mobility-shift
      assays demonstrated an induction of a kappa beta-binding activity in hippocampal
      cells exposed to TNFs. Exposure of cultures to I kappa B (MAD3) antisense
      oligonucleotides, a manipulation designed to induce NF-kappa B, mimicked the
      protection by TNFs. These data suggest that TNFs protect hippocampal neurons
      against A beta toxicity by suppressing accumulation of ROS and Ca2+ and that
      kappa B-dependent transcription is sufficient to mediate these effects. A
      modulatory role for TNF in the neurodegenerative process in AD is proposed.

PMID- 7568128
TI  - Hydrophobic cluster analysis predicts an amino-terminal domain of varicella
      zoster virus open reading frame 10 required for transcriptional activation.
AB  - Varicella-zoster virus open reading frame 10 (ORF10) protein, the homolog of the
      herpes simplex virus protein VP16, can transactivate immediate-early promoters
      from both viruses. A protein sequence comparison procedure termed hydrophobic
      cluster analysis was used to identify a motif centered at Phe-28, near the amino
      terminus of ORF10, that strongly resembles the sequence of the activating domain
      surrounding Phe-442 of VP16. With a series of GAL4-ORF10 fusion proteins, we
      mapped the ORF10 transcriptional-activation domain to the amino-terminal region
      (aa 5-79). Extensive mutagenesis of Phe-28 in GAL4-ORF10 fusion proteins
      demonstrated the importance of an aromatic or bulky hydrophobic amino acid at
      this position, as shown previously for Phe-442 of VP16. Transactivation by the
      native ORF10 protein was abolished when Phe-28 was replaced by Ala. Similar amino
      terminal domains were identified in the VP16 homologs of other
      alphaherpesviruses. Hydrophobic cluster analysis correctly predicted activation
      domains of ORF10 and VP16 that share critical characteristics of a distinctive
      subclass of acidic activation domains.

PMID- 7568130
TI  - Rabbit monoclonal antibodies: generating a fusion partner to produce rabbit
      rabbit hybridomas.
AB  - During the last 15 years several laboratories have attempted to generate rabbit
      monoclonal antibodies, mainly because rabbits recognize antigens and epitopes
      that are not immunogenic in mice or rats, two species from which monoclonal
      antibodies are usually generated. Monoclonal antibodies from rabbits could not be
      generated, however, because a plasmacytoma fusion partner was not available. To
      obtain a rabbit plasmacytoma cell line that could be used as a fusion partner we
      generated transgenic rabbits carrying two transgenes, c-myc and v-abl. These
      rabbits developed plasmacytomas, and we obtained several plasmacytoma cell lines
      from which we isolated hypoxanthine/aminopterin/thymidine-sensitive clones. One
      of these clones, when fused with spleen cells of immunized rabbits, produced
      stable hybridomas that secreted antibodies specific for the immunogen. The
      hybridomas can be cloned and propagated in nude mice, and they can be frozen
      without change in their ability to secrete specific monoclonal antibodies. These
      rabbit-rabbit hybridomas will be useful not only for production of monoclonal
      antibodies but also for studies of immunoglobulin gene rearrangements and isotype
      switching.

PMID- 7568129
TI  - The only essential function of TFIIIA in yeast is the transcription of 5S rRNA
      genes.
AB  - We have developed a system to transcribe the yeast 5S rRNA gene in the absence of
      the transcription factor TFIIIA. A long transcript was synthesized both in vitro
      and in vivo from a hybrid gene in which the tRNA-like promoter sequence of the
      RPR1 gene was fused to the yeast 5S RNA gene. No internal initiation directed by
      the endogenous 5S rDNA promoter or any processing of the hybrid transcript was
      observed in vitro. Yeast cells devoid of transcription factor TFIIIA, which,
      therefore, could not synthesize any 5S rRNA from the endogenous chromosomal
      copies of 5S rDNA, could survive if they carried the hybrid RPR1-5S construct on
      a multicopy plasmid. In this case, the only source of 5S rRNA was the precursor
      RPR1-5S transcript that gave rise to two RNA species slightly larger than wild
      type 5S rRNA. This establishes that the only essential function of TFIIIA is to
      promote the synthesis of 5S rRNA. However, cells devoid of TFIIIA and surviving
      with these two RNAs grew more slowly at 30 degrees C compared with wild-type
      cells and were thermosensitive at 37 degrees C.

PMID- 7568131
TI  - A membrane-associated form of sucrose synthase and its potential role in
      synthesis of cellulose and callose in plants.
AB  - Sucrose synthase (SuSy; EC 2.4.1.13; sucrose + UDP reversible UDPglucose +
      fructose) has always been studied as a cytoplasmic enzyme in plant cells where it
      serves to degrade sucrose and provide carbon for respiration and synthesis of
      cell wall polysaccharides and starch. We report here that at least half of the
      total SuSy of developing cotton fibers (Gossypium hirsutum) is tightly associated
      with the plasma membrane. Therefore, this form of SuSy might serve to channel
      carbon directly from sucrose to cellulose and/or callose synthases in the plasma
      membrane. By using detached and permeabilized cotton fibers, we show that carbon
      from sucrose can be converted at high rates to both cellulose and callose.
      Synthesis of cellulose or callose is favored by addition of EGTA or calcium and
      cellobiose, respectively. These findings contrast with the traditional
      observation that when UDPglucose is used as substrate in vitro, callose is the
      major product synthesized. Immunolocalization studies show that SuSy can be
      localized at the fiber surface in patterns consistent with the deposition of
      cellulose or callose. Thus, these results support a model in which SuSy exists in
      a complex with the beta-glucan synthases and serves to channel carbon from
      sucrose to glucan.

PMID- 7568132
TI  - A second nitrogenase in vegetative cells of a heterocyst-forming cyanobacterium.
AB  - In many filamentous cyanobacteria nitrogen fixation occurs in differentiated
      cells called heterocysts. Filamentous strains that do not form heterocysts may
      fix nitrogen in vegetative cells, primarily under anaerobic conditions. We
      describe here two functional Mo-dependent nitrogenases in a single organism, the
      cyanobacterium Anabaena variabilis. Using a lacZ reporter with a fluorescent beta
      galactoside substrate for in situ localization of gene expression, we have shown
      that the two clusters of nif genes are expressed independently. One nitrogenase
      functions only in heterocysts under either aerobic or anaerobic growth
      conditions, whereas the second nitrogenase functions only under anaerobic
      conditions in vegetative cells and heterocysts. Differences between the two nif
      clusters suggest that the nitrogenase that is expressed in heterocysts is
      developmentally regulated while the other is regulated by environmental factors.

PMID- 7568133
TI  - A biomarker that identifies senescent human cells in culture and in aging skin in
      vivo.
AB  - Normal somatic cells invariably enter a state of irreversibly arrested growth and
      altered function after a finite number of divisions. This process, termed
      replicative senescence, is thought to be a tumor-suppressive mechanism and an
      underlying cause of aging. There is ample evidence that escape from senescence,
      or immortality, is important for malignant transformation. By contrast, the role
      of replicative senescence in organismic aging is controversial. Studies on cells
      cultured from donors of different ages, genetic backgrounds, or species suggest
      that senescence occurs in vivo and that organismic lifespan and cell replicative
      lifespan are under common genetic control. However, senescent cells cannot be
      distinguished from quiescent or terminally differentiated cells in tissues. Thus,
      evidence that senescent cells exist and accumulate with age in vivo is lacking.
      We show that several human cells express a beta-galactosidase, histochemically
      detectable at pH 6, upon senescence in culture. This marker was expressed by
      senescent, but not presenescent, fibroblasts and keratinocytes but was absent
      from quiescent fibroblasts and terminally differentiated keratinocytes. It was
      also absent from immortal cells but was induced by genetic manipulations that
      reversed immortality. In skin samples from human donors of different age, there
      was an age-dependent increase in this marker in dermal fibroblasts and epidermal
      keratinocytes. This marker provides in situ evidence that senescent cells may
      exist and accumulate with age in vivo.

PMID- 7568134
TI  - Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.
AB  - Transgenic Caenorhabditis elegans nematodes have been engineered to express
      potentially amyloidic human proteins. These animals contain constructs in which
      the muscle-specific unc-54 promoter/enhancer of C. elegans drives the expression
      of the appropriate coding regions derived from human cDNA clones. Animals
      containing constructs expressing the 42-amino acid beta-amyloid peptide (derived
      from human amyloid precursor protein cDNA) produce muscle-specific deposits
      immunoreactive with anti-beta-amyloid polyclonal and monoclonal antibodies. A
      subset of these deposits also bind the amyloid-specific dye thioflavin S,
      indicating that these deposits have the tinctural characteristics of classic
      amyloid. Co-expression of beta-peptide and transthyretin, a protein implicated in
      preventing the formation of insoluble beta-amyloid, leads to a dramatic reduction
      in the number of dye-reactive deposits. These results suggest that this
      invertebrate model may be useful for in vivo investigation of factors that
      modulate amyloid formation.

PMID- 7568136
TI  - A mammalian arginine/lysine transporter uses multiple promoters.
AB  - The mCAT-2 gene encodes a Na(+)-independent cationic amino acid (AA) transporter
      that is inducibly expressed in a tissue-specific manner in various physiological
      conditions. When mCAT-2 protein is expressed in Xenopus oocytes, the elicited AA
      transport properties are similar to the biochemically defined transport system
      y+. The mCAT-2 protein sequence is closely related to another cationic AA
      transporter (mCAT-1); these related proteins elicit virtually identical cationic
      AA transport in Xenopus oocytes. The two genes differ in their tissue expression
      and induction patterns. Here we report the presence of diverse 5' untranslated
      region (UTR) sequences in mCAT-2 transcripts. Sequence analysis of 22 independent
      mCAT-2 cDNA clones reveals that the cDNA sequences converge precisely 16 bp 5' of
      the initiator AUG codon. Moreover, analysis of genomic clones shows that the mCAT
      2 gene 5'UTR exons are dispersed over 18 kb. Classical promoter and enhancer
      elements are present in appropriate positions 5' of the exons and their
      utilization results in regulated mCAT-2 mRNA accumulation in skeletal muscle and
      liver following partial hepatectomy. The isoform adjacent to the most distal
      promoter is found in all tissues and cell types previously shown to express mCAT
      2, while the other 5' UTR isoforms are more tissue specific in their expression.
      Utilization of some or all of five putative promoters was documented in lymphoma
      cell clones, liver, and skeletal muscle. TATA-containing and (G+C)-rich TATA-less
      promoters appear to control mCAT-2 gene expression. The data indicate that the
      several distinct 5' mCAT-2 mRNA isoforms result from transcriptional initiation
      at distinct promoters and permit flexible transcriptional regulation of this
      cationic AA transporter gene.

PMID- 7568135
TI  - Plant members of a family of sulfate transporters reveal functional subtypes.
AB  - Three plant sulfate transporter cDNAs have been isolated by complementation of a
      yeast mutant with a cDNA library derived from the tropical forage legume
      Stylosanthes hamata. Two of these cDNAs, shst1 and shst2, encode high-affinity
      H+/sulfate cotransporters that mediate the uptake of sulfate by plant roots from
      low concentrations of sulfate in the soil solution. The third, shst3, represents
      a different subtype encoding a lower affinity H+/sulfate cotransporter, which may
      be involved in the internal transport of sulfate between cellular or subcellular
      compartments within the plant. The steady-state level of mRNA corresponding to
      both subtypes is subject to regulation by signals that ultimately respond to the
      external sulfate supply. These cDNAs represent the identification of plant
      members of a family of related sulfate transporter proteins whose sequences
      exhibit significant amino acid conservation in filamentous fungi, yeast, plants,
      and mammals.

PMID- 7568137
TI  - Sequence-specific inhibition of human immunodeficiency virus (HIV) reverse
      transcription by antisense oligonucleotides: comparative study in cell-free
      assays and in HIV-infected cells.
AB  - We have investigated two regions of the viral RNA of human immunodeficiency virus
      type 1 (HIV-1) as potential targets for antisense oligonucleotides. An
      oligodeoxynucleotide targeted to the U5 region of the viral genome was shown to
      block the elongation of cDNA synthesized by HIV-1 reverse transcriptase in vitro.
      This arrest of reverse transcription was independent of the presence of RNase H
      activity associated with the reverse transcriptase enzyme. A second
      oligodeoxynucleotide targeted to a site adjacent to the primer binding site
      inhibited reverse transcription in an RNase H-dependent manner. These two
      oligonucleotides were covalently linked to a poly(L-lysine) carrier and tested
      for their ability to inhibit HIV-1 infection in cell cultures. Both
      oligonucleotides inhibited virus production in a sequence- and dose-dependent
      manner. PCR analysis showed that they inhibited proviral DNA synthesis in
      infected cells. In contrast, an antisense oligonucleotide targeted to the tat
      sequence did not inhibit proviral DNA synthesis but inhibited viral production at
      a later step of virus development. These experiments show that antisense
      oligonucleotides targeted to two regions of HIV-1 viral RNA can inhibit the first
      step of viral infection--i.e., reverse transcription--and prevent the synthesis
      of proviral DNA in cell cultures.

PMID- 7568139
TI  - The amino-terminal domain of the prokaryotic enhancer-binding protein XylR is a
      specific intramolecular repressor.
AB  - The mechanism under which the signal-reception amino-terminal portion (A domain)
      of the prokaryotic enhancer-binding protein XylR controls the activity of the
      regulator has been investigated through complementation tests in vivo, in which
      the various protein segments were produced as independent polypeptides. Separate
      expression of the A domain repressed the otherwise constitutive activity of a
      truncated derivative of XylR deleted of its A domain (XylR delta A). Such
      inhibition was not released by m-xylene, the natural inducer of the system.
      Repression caused by the A domain was specific for XylR because it did not affect
      activation of the sigma 54 promoter PnifH by a derivative of its cognate
      regulator, NifA, deleted of its own A domain. The A domain was also unable to
      repress the activity of a NifA-XylR hybrid protein resulting from fusing two
      thirds of the central domain of NifA to the carboxyl-terminal third of XylR,
      which includes its DNA-binding domain. The inhibitory effect caused by the A
      domain of XylR on XylR delta A seems, therefore, to result from specific
      interactions in trans between the two truncated proteins and not from mere
      hindering of an activating surface.

PMID- 7568138
TI  - The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density
      lipoprotein subfractions.
AB  - The aim of our study was to investigate the relationships between the levels of
      coenzyme Q10 (CoQ10) and vitamin E and the levels of hydroperoxide in three
      subfractions of low density lipoproteins (LDL) that were isolated from healthy
      donors. LDL3, the densest of the three subfractions, has shown statistically
      significant lower levels of CoQ10 and vitamin E, which were associated with
      higher hydroperoxide levels when compared with the lighter counterparts. After
      CoQ10 supplementation, all three LDL subfractions had significantly increased
      CoQ10 levels. In particular, LDL3 showed the highest CoQ10 increase when compared
      with LDL1 and LDL2 and was associated with a significant decrease in
      hydroperoxide level. These results support the hypothesis that the CoQ10
      endowment in subfractions of LDL affects their oxidizability, and they have
      important implications for the treatment of disease.

PMID- 7568140
TI  - A secretion inhibitory signal transduction molecule on mast cells is another C
      type lectin.
AB  - Secretion of inflammatory mediators by rat mast cells (line RBL-2H3) was earlier
      shown to be inhibited upon clustering a membrane glycoprotein by monoclonal
      antibody G63. This glycoprotein, named mast cell function-associated antigen
      (MAFA), was also shown to interfere with the coupling cascade of the type 1 Fc
      epsilon receptor upstream to phospholipase C gamma 1 activation by protein
      tyrosine kinases. Here we report that the MAFA is expressed as both a monomer and
      a homodimer. Expression cloning of its cDNA shows that it contains a single open
      reading frame, encoding a 188-amino acid-long type II integral membrane protein.
      The 114 C-terminal amino acids display sequence homology with the carbohydrate
      binding domain of calcium-dependent animal lectins, many of which have
      immunological functions. The cytoplasmic tail of MAFA contains a YXXL (YSTL)
      motif, which is conserved among related C-type lectins and is an essential
      element in the immunoreceptor tyrosine-based activation motifs. Finally, changes
      in the MAFA tyrosyl- and seryl-phosphorylation levels are observed in response to
      monoclonal antibody G63 binding, antigenic stimulation, and a combination of both
      treatments.

PMID- 7568141
TI  - Identification of the overtone of the Fe-CO stretching mode in heme proteins: a
      probe of the heme active site.
AB  - Two CO-isotope sensitive lines have been detected in the overtone region of the
      resonance Raman spectra of CO-bound hemeproteins. One line is assigned as the
      overtone of the Fe-CO stretching mode and is located in the 1000- to 1070-cm-1
      region. The other line is found in the 1180- to 1210-cm-1 region and is assigned
      as a combination between a porphyrin mode, nu 7, and the Fe-CO stretching mode.
      The high intensities of these lines, which in the terminal oxidase class of
      proteins are of the same order as those of the fundamental stretching mode,
      indicate that the mechanism of enhancement for modes involving the Fe-CO moiety
      is different from that for the modes of the porphyrin macrocycle and call for
      reexamination of Raman theory of porphyrins as applied to axial ligands. The
      anharmonicity of the electronic potential function was evaluated, revealing that
      in the terminal oxidases the anharmonicity is greater than in the other heme
      proteins that were examined, suggesting a distinctive interaction of the bound CO
      with its distal environment in this family. Furthermore, the anharmonicity
      correlates with the frequency of the C-O stretching mode, demonstrating that both
      of these parameters are sensitive to the Fe-CO bond energy. The overtone and
      combination lines involving the bound CO promise to be additional probes of heme
      protein structural properties.

PMID- 7568142
TI  - Oligomeric structure of caveolin: implications for caveolae membrane
      organization.
AB  - A 22-kDa protein, caveolin, is localized to the cytoplasmic surface of plasma
      membrane specializations called caveolae. We have proposed that caveolin may
      function as a scaffolding protein to organize and concentrate signaling molecules
      within caveolae. Here, we show that caveolin interacts with itself to form
      homooligomers. Electron microscopic visualization of these purified caveolin
      homooligomers demonstrates that they appear as individual spherical particles. By
      using recombinant expression of caveolin as a glutathione S-transferase fusion
      protein, we have defined a region of caveolin's cytoplasmic N-terminal domain
      that mediates these caveolin-caveolin interactions. We suggest that caveolin
      homooligomers may function to concentrate caveolin-interacting molecules within
      caveolae. In this regard, it may be useful to think of caveolin homooligomers as
      "fishing lures" with multiple "hooks" or attachment sites for caveolin
      interacting molecules.

PMID- 7568143
TI  - The 37/40-kilodalton autoantigen in insulin-dependent diabetes mellitus is the
      putative tyrosine phosphatase IA-2.
AB  - Major targets for autoantibodies associated with the development of insulin
      dependent diabetes mellitus (IDDM) include tryptic fragments with a molecular
      mass of 37 kDa and/or 40 kDa of a pancreatic islet cell antigen of unknown
      identity. The assay identifying autoantibodies against the 37/40-kDa antigen in
      human sera is based on the immunoprecipitation of 35S-labeled rat insulinoma cell
      proteins with sera from IDDM patients, followed by limited trypsin digestion of
      the immunoprecipitated material. To identify cDNA clones coding for the 37/40-kDa
      antigen, we have screened a cDNA expression library from rat insulinoma cells
      with a serum from an IDDM patient that precipitated the 37/40-kDa antigen in our
      assay. Among the cDNA products that reacted with the IDDM serum, we identified
      one cDNA clone whose open reading frame encodes a protein with a predicted mass
      of 105 kDa that we termed "ICA105" for 105-kDa islet cell antibody. The deduced
      amino acid sequence has high homology to a recently cloned putative tyrosine
      phosphatase IA-2 from human and mouse cDNA libraries. Translation of the cDNA in
      vitro results in a polypeptide with the expected molecular mass of 105 kDa. The
      evidence that ICA105 is indeed the precursor of the 37/40-kDa tryptic fragments
      is based on the following three results: (i) Sera from IDDM patients containing
      autoantibodies to the 37/40-kDa antigen precipitate the in vitro translated
      polypeptide, whereas sera from healthy subjects as well as sera from IDDM
      patients not reactive with the 37/40-kDa antigen do not precipitate the cDNA
      product. (ii) Immunoprecipitation of the in vitro translated protein with sera
      containing autoantibodies to the 37/40-kDa antigen followed by limited trypsin
      digestion of the precipitated proteins results in a 40-kDa polypeptide. (iii) The
      protein derived from our cDNA but not from an unrelated control cDNA clone can
      block immunoprecipitation of the 37/40-kDa antigen from a labeled rat insulinoma
      cell extract. The availability of the cloned 37/40-kDa antigen should facilitate
      the identification of individuals at risk of IDDM with increased accuracy.
      Furthermore, the identification of the 37/40-kDa antigen as the putative tyrosine
      phosphatase IA-2 is of relevance in elucidating the role of this antigen in the
      development of IDDM.

PMID- 7568144
TI  - Cone photoreceptors respond to their own glutamate release in the tiger
      salamander.
AB  - Pulse-like currents resembling miniature postsynaptic currents were recorded in
      patch-clamped isolated cones from the tiger salamander retina. The events were
      absent in isolated cones without synaptic terminals. The frequency of events was
      increased by either raising the osmotic pressure or depolarizing the cell. It was
      decreased by the application of either glutamate or the glutamate-transport
      blockers dihydrokainate and D,L-threo-3-hydroxyaspartate. The events required
      external Na+ for which Li+ could not substitute. The reversal potential of these
      currents followed the equilibrium potential for Cl- when internal Cl-
      concentration was changed. Thus, these miniature currents appear to represent the
      presynaptic activation of the glutamate receptor with glutamate transporter-like
      pharmacology, caused by the photoreceptor's own vesicular glutamate release.
      Using a noninvasive method to preserve the intracellular Cl- concentration, we
      showed that glutamate elicits an outward current in isolated cones. Fluorescence
      of the membrane-permeable form of fura-2 was used to monitor Ca2+ entry at the
      cone terminal as a measure of membrane depolarization. The increase in
      intracellular Ca2+ concentration, elicited by puff application of 30 mM KCl, was
      completely suppressed in the presence of 100 microM glutamate. Puff application
      of glutamate alone had no measurable depolarizing effect. These results suggest
      that the equilibrium potential for Cl-, ECl, was more negative than the
      activation range for Ca2+ channels and that glutamate elicited an outward
      current, hyperpolarizing the cones.

PMID- 7568145
TI  - Mutation of conserved negatively charged residues in the S2 and S3 transmembrane
      segments of a mammalian K+ channel selectively modulates channel gating.
AB  - Voltage-gated channel proteins sense a change in the transmembrane electric field
      and respond with a conformational change that allows ions to diffuse across the
      pore-forming structure. Site-specific mutagenesis combined with
      electrophysiological analysis of expressed mutants in amphibian oocytes has
      previously established the S4 transmembrane segment as an element of the voltage
      sensor. Here, we show that mutations of conserved negatively charged residues in
      S2 and S3 of a brain K+ channel, thought of as countercharges for the positively
      charged residues in S4, selectively modulate channel gating without modifying the
      permeation properties. Mutations of Glu235 in S2 that neutralize or reverse
      charge increase the probability of channel opening and the apparent gating
      valence. In contrast, replacements of Glu272 by Arg or Thr268 by Asp in S3
      decrease the open probability and the apparent gating valence. Residue Glu225 in
      S2 tolerated replacement only by acidic residues, whereas Asp258 in S3 was
      intolerant to any attempted change. These results imply that S2 and S3 are
      unlikely to be involved in channel lining, yet, together with S4, may be
      additional components of the voltage-sensing structure.

PMID- 7568147
TI  - Long-term repopulation of hematolymphoid cells with only a few hemopoietic stem
      cells in mice.

PMID- 7568146
TI  - Multiple N-acyl-L-homoserine lactone signal molecules regulate production of
      virulence determinants and secondary metabolites in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa produces a spectrum of exoproducts many of which have been
      implicated in the pathogenesis of human infection. Expression of some of these
      factors requires cell-cell communication involving the interaction of a small
      diffusible molecule, an "autoinducer," with a positive transcriptional activator.
      In P. aeruginosa PAO1, LasI directs the synthesis of the autoinducer N-(3
      oxododecanoyl)-L-homoserine lactone (OdDHL), which activates the positive
      transcriptional activator, LasR. Recently, we have discovered a second signaling
      molecule-based modulon in PAO1, termed vsm, which contains the genes vsmR and
      vsmI. Using HPLC, mass spectrometry, and NMR spectroscopy we now establish that
      in Escherichia coli, VsmI directs the synthesis of N-butanoyl-L-homoserine
      lactone (BHL) and N-hexanoyl-L-homoserine lactone (HHL). These compounds are
      present in the spent culture supernatants of P. aeruginosa in a molar ratio of
      approximately 15:1 and their structures were unequivocally confirmed by chemical
      synthesis. Addition of either BHL or HHL to PAN067, a pleiotropic P. aeruginosa
      mutant unable to synthesize either of these autoinducers, restored elastase,
      chitinase, and cyanide production. In E. coli carrying a vsmR/vsmI'::lux
      transcriptional fusion, BHL and HHL activated VsmR to a similar extent. Analogues
      of these N-acyl-L-homoserine lactones in which the N-acyl side chain has been
      extended and/or oxidized at the C-3 position exhibit substantially lower activity
      (e.g., OdDHL) or no activity (e.g., dDHL) in this lux reporter assay. These data
      indicate that multiple families of quorum sensing modulons interactively regulate
      gene expression in P. aeruginosa.

PMID- 7568148
TI  - The nascent-polypeptide-associated complex: having a "NAC" for fidelity in
      translocation.

PMID- 7568149
TI  - The intrinsic ability of ribosomes to bind to endoplasmic reticulum membranes is
      regulated by signal recognition particle and nascent-polypeptide-associated
      complex.
AB  - Signal peptides direct the cotranslational targeting of nascent polypeptides to
      the endoplasmic reticulum (ER). It is currently believed that the signal
      recognition particle (SRP) mediates this targeting by first binding to signal
      peptides and then by directing the ribosome/nascent chain/SRP complex to the SRP
      receptor at the ER. We show that ribosomes can mediate targeting by directly
      binding to translocation sites. When purified away from cytosolic factors,
      including SRP and nascent-polypeptide-associated complex (NAC), in vitro
      assembled translation intermediates representing ribosome/nascent-chain complexes
      efficiently bound to microsomal membranes, and their nascent polypeptides could
      subsequently be efficiently translocated. Because removal of cytosolic factors
      from the ribosome/nascent-chain complexes also resulted in mistargeting of
      signalless nascent polypeptides, we previously investigated whether readdition of
      cytosolic factors, such as NAC and SRP, could restore fidelity to targeting.
      Without SRP, NAC prevented all nascent-chain-containing ribosomes from binding to
      the ER membrane. Furthermore, SRP prevented NAC from blocking ribosome-membrane
      association only when the nascent polypeptide contained a signal. Thus, NAC is a
      global ribosome-binding prevention factor regulated in activity by signal-peptide
      directed SRP binding. A model presents ribosomes as the targeting vectors for
      delivering nascent polypeptides to translocation sites. In conjunction with
      signal peptides, SRP and NAC contribute to this specificity of ribosomal function
      by regulating exposure of a ribosomal membrane attachment site that binds to
      receptors in the ER membrane.

PMID- 7568150
TI  - Role of aromatic residues in stabilization of the [Fe4S4] cluster in high
      potential iron proteins (HiPIPs): physical characterization and stability studies
      of Tyr-19 mutants of Chromatium vinosum HiPIP.
AB  - The functional role of residue Tyr-19 of Chromatium vinosum HiPIP has been
      evaluated by site-directed mutagenesis experiments. The stability of the [Fe4S4]
      cluster prosthetic center is sensitive to side-chain replacements. Polar residues
      result in significant instability, while nonpolar residues (especially with
      aromatic side chains) maintain cluster stability. Two-dimensional NMR data of
      native and mutant HiPIPs are consistent with a model where Tyr-19 serves to
      preserve the structural rigidity of the polypeptide backbone, thereby maintaining
      a hydrophobic barrier for exclusion of water from the cluster cavity. Solvent
      accessibility results in more facile oxidation of the cluster by atmospheric
      oxygen, with subsequent rapid hydrolysis of the [Fe4S4]3+ core.

PMID- 7568151
TI  - Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form
      homo- and heterodimers in vivo.
AB  - The yeast two-hybrid system and far-Western protein blot analysis were used to
      demonstrate dimerization of human double-stranded RNA (dsRNA)-dependent protein
      kinase (PKR) in vivo and in vitro. A catalytically inactive mutant of PKR with a
      single amino acid substitution (K296R) was found to dimerize in vivo, and a
      mutant with a deletion of the catalytic domain of PKR retained the ability to
      dimerize. In contrast, deletion of the two dsRNA-binding motifs in the N-terminal
      regulatory domain of PKR abolished dimerization. In vitro dimerization of the
      dsRNA-binding domain required the presence of dsRNA. These results suggest that
      the binding of dsRNA by PKR is necessary for dimerization. The mammalian dsRNA
      binding protein TRBP, originally identified on the basis of its ability to bind
      the transactivation region (TAR) of human immunodeficiency virus RNA, also
      dimerized with itself and with PKR in the yeast assay. Taken together, these
      results suggest that complexes consisting of different combinations of dsRNA
      binding proteins may exist in vivo. Such complexes could mediate differential
      effects on gene expression and control of cell growth.

PMID- 7568152
TI  - Role of the GATA factors Gln3p and Nil1p of Saccharomyces cerevisiae in the
      expression of nitrogen-regulated genes.
AB  - We have isolated the NIL1 gene, whose product is an activator of the
      transcription of nitrogen-regulated genes, by virtue of the homology of its zinc
      finger domain to that of the previously identified activator, the product of
      GLN3. Disruption of the chromosomal NIL1 gene enabled us to compare the effects
      of Gln3p and of Nil1p on the expression of the nitrogen-regulated genes GLN1,
      GDH2, and GAP1, coding respectively for glutamine synthetase, NAD-linked
      glutamate dehydrogenase, and general amino acid permease. Our results show that
      the nature of GATAAG sequence that serve as the upstream activation sequence
      elements for these genes determines their abilities to respond to Gln3p and
      Nil1p. The results further indicate that Gln3p is inactivated by an increase in
      the intracellular concentration of glutamine and that Nil1p is inactivated by an
      increase in intracellular glutamate.

PMID- 7568153
TI  - The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation.
AB  - p53 accumulates after DNA damage and arrests cellular growth. These findings
      suggest a possible role for p53 in the cellular response to DNA damage. We have
      previously shown that the C terminus of p53 binds DNA nonspecifically and
      assembles stable tetramers. In this study, we have utilized purified segments of
      human and murine p53s to determine which p53 domains may participate in a DNA
      damage response pathway. We find that the C-terminal 75 amino acids of human or
      murine p53 are necessary and sufficient for the DNA annealing and strand-transfer
      activities of p53. In addition, both full-length wild-type p53 and the C-terminal
      75 amino acids display an increased binding affinity for DNA damaged by
      restriction digestion, DNase I treatment, or ionizing radiation. In contrast, the
      central site-specific DNA-binding domain together with the tetramerization domain
      does not have these activities. We propose that interactions of the C terminus of
      p53 with damaged DNA may play a role in the activation of p53 in response to DNA
      damage.

PMID- 7568155
TI  - A recessive mutation, immune deficiency (imd), defines two distinct control
      pathways in the Drosophila host defense.
AB  - In this paper we report a recessive mutation, immune deficiency (imd), that
      impairs the inducibility of all genes encoding antibacterial peptides during the
      immune response of Drosophila. When challenged with bacteria, flies carrying this
      mutation show a lower survival rate than wild-type flies. We also report that, in
      contrast to the antibacterial peptides, the antifungal peptide drosomycin remains
      inducible in a homozygous imd mutant background. These results point to the
      existence of two different pathways leading to the expression of two types of
      target genes, encoding either the antibacterial peptides or the antifungal
      peptide drosomycin.

PMID- 7568154
TI  - The preimplantation mouse embryo is a target for cannabinoid ligand-receptor
      signaling.
AB  - Using a reverse transcription-coupled PCR, we demonstrated that both brain and
      spleen type cannabinoid receptor (CB1-R and CB2-R, respectively) mRNAs are
      expressed in the preimplantation mouse embryo. The CB1-R mRNA expression was
      coincident with the activation of the embryonic genome late in the two-cell
      stage, whereas the CB2-R mRNA was present from the one-cell through the
      blastocyst stages. The major psychoactive component of marijuana (-)-delta-9
      tetrahydrocannabinol [(-)-THC] inhibited forskolin-stimulated cAMP generation in
      the blastocyst, and this inhibition was prevented by pertussis toxin. However,
      the inactive cannabinoid cannabidiol (CBD) failed to influence this response.
      These results suggest that cannabinoid receptors in the embryo are coupled to
      inhibitory guanine nucleotide binding proteins. Further, the oviduct and uterus
      exhibited the enzymatic capacity to synthesize the putative endogenous
      cannabinoid ligand arachidonylethanolamide (anandamide). Synthetic and natural
      cannabinoid agonists [WIN 55,212-2, CP 55,940, (-)-THC, and anandamide], but not
      CBD or arachidonic acid, arrested the development of two-cell embryos primarily
      between the four-cell and eight-cell stages in vitro in a dose-dependent manner.
      Anandamide also interfered with the development of eight-cell embryos to
      blastocysts in culture. The autoradiographic studies readily detected binding of
      [3H]anandamide in embryos at all stages of development. Positive signals were
      present in one-cell embryos and all blastomeres of two-cell through four-cell
      embryos. However, most of the binding sites in eight-cell embryos and morulae
      were present in the outer cells. In the blastocyst, these signals were primarily
      localized in the mural trophectoderm with low levels of signals in the polar
      trophectoderm, while little or no signals were noted in inner cell mass cells.
      These results establish that the preimplantation mouse embryo is a target for
      cannabinoid ligands. Consequently, many of the adverse effects of cannabinoids
      observed during pregnancy could be mediated via these cannabinoid receptors.
      Although the physiological significance of the cannabinoid ligand-receptor
      signaling in normal preimplantation embryo development is not yet clear, the
      regulation of embryonic cAMP and/or Ca2+ levels via this signaling pathway may be
      important for normal embryonic development and/or implantation.

PMID- 7568156
TI  - The silver gene of Drosophila melanogaster encodes multiple carboxypeptidases
      similar to mammalian prohormone-processing enzymes.
AB  - The silver (svr) gene of Drosophila melanogaster is required for viability, and
      severe mutant alleles result in death prior to eclosion. Adult flies homozygous
      or hemizygous for weaker alleles display several visible phenotypes, including
      cuticular structures that are pale and silvery in color due to reduced
      melanization. We have identified and cloned the DNA encoding the svr gene and
      determined the sequence of several partially overlapping cDNAs derived from svr
      mRNAs. The predicted amino acid sequence of the polypeptides encoded by these
      cDNAs indicates that the silver proteins are members of the family of preprotein
      processing carboxypeptidases that includes the human carboxypeptidases E, M, and
      N. One class of svr mRNAs is alternatively spliced to encode at least two
      polyproteins, each of which is composed of two carboxypeptidase domains.

PMID- 7568157
TI  - Aspirin triggers previously undescribed bioactive eicosanoids by human
      endothelial cell-leukocyte interactions.
AB  - Aspirin [acetylsalicylic acid (ASA)], along with its analgesic-antipyretic uses,
      is now also being considered for cardiovascular protection and treatments in
      cancer and human immunodeficiency virus infection. Although many of ASA's
      pharmacological actions are related to its ability to inhibit prostaglandin and
      thromboxane biosynthesis, some of its beneficial therapeutic effects are not
      completely understood. Here, ASA triggered transcellular biosynthesis of a
      previously unrecognized class of eicosanoids during coincubations of human
      umbilical vein endothelial cells (HUVEC) and neutrophils [polymorphonuclear
      leukocytes (PMN)]. These eicosanoids were generated with ASA but not by
      indomethacin, salicylate, or dexamethasone. Formation was enhanced by cytokines
      (interleukin 1 beta) that induced the appearance of prostaglandin G/H synthase 2
      (PGHS-2) but not 15-lipoxygenase, which initiates their biosynthesis from
      arachidonic acid in HUVEC. Costimulation of HUVEC/PMN by either thrombin plus the
      chemotactic peptide fMet-Leu-Phe or phorbol 12-myristate 13-acetate or ionophore
      A23187 leads to the production of these eicosanoids from endogenous sources. Four
      of these eicosanoids were also produced when PMN were exposed to 15R-HETE [(15R)
      15-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid] and an agonist. Physical
      methods showed that the class consists of four tetraene-containing products from
      arachidonic acid that proved to be 15R-epimers of lipoxins. Two of these
      compounds (III and IV) were potent inhibitors of leukotriene B4-mediated PMN
      adhesion to HUVEC, with compound IV [(5S,6R,15R)-5,6,15-trihydroxy-7,9,13-trans
      11-cis-eicosatetraenoi c acid; 15-epilipoxin A4] active in the nanomolar range.
      These results demonstrate that ASA evokes a unique class of eicosanoids formed by
      acetylated PGHS-2 and 5-lipoxygenase interactions, which may contribute to the
      therapeutic impact of this drug. Moreover, they provide an example of a drug's
      ability to pirate endogenous biosynthetic mechanisms to trigger new mediators.

PMID- 7568159
TI  - Introduction of the transposable element Minos into the germ line of Drosophila
      melanogaster.
AB  - A transposon based on the transposable element Minos from Drosophila hydei was
      introduced into the genome of Drosophila melanogaster using transformation
      mediated by the Minos transposase. The transposon carries a wild-type version of
      the white gene (w) of Drosophila inserted into the second exon of Minos.
      Transformation was obtained by injecting the transposon into preblastoderm
      embryos that were expressing transposase either from a Hsp70-Minos fusion
      inserted into the genome via P-element-mediated transformation or from a
      coinjected plasmid carrying the Hsp70-Minos fusion. Between 1% and 6% of the
      fertile injected individuals gave transformed progeny. Four of the insertions
      were cloned and the DNA sequences flanking the transposon ends were determined.
      The "empty" sites corresponding to three of the insertions were amplified from
      the recipient strain by PCR, cloned, and sequenced. In all cases, the transposon
      has inserted into a TA dinucleotide and has created the characteristic TA target
      site duplication. In the absence of transposase, the insertions were stable in
      the soma and the germ line. However, in the presence of the Hsp70-Minos gene the
      Minos-w transposon excises, resulting in mosaic eyes and germ-line reversion to
      the white phenotype. Minos could be utilized as an alternative to existing
      systems for transposon tagging and enhancer trapping in Drosophila; it might also
      be of use as a germ-line transformation vector for non-Drosophila insects.

PMID- 7568158
TI  - Low density lipoprotein receptor-related protein mediates apolipoprotein E
      dependent neurite outgrowth in a central nervous system-derived neuronal cell
      line.
AB  - The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for
      Alzheimer disease, suggesting that apoE may directly influence neurons in the
      aging brain. Recent data suggest that apoE-containing lipoproteins can influence
      neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE
      effects have not been clarified. We show here that in a central nervous system
      derived neuronal cell line, apoE3 but not apoE4 increases neurite extension. The
      effect of apoE3 was blocked at low nanomolar concentrations by purified 39-kDa
      protein that regulates ligand binding to the low density lipoprotein receptor
      related protein (LRP). Anti-LRP antibody also completely abolished the neurite
      promoting effect of apoE3. Understanding isoform-specific cell biological
      processes mediated by apoE-LRP interactions in central nervous system neurons may
      provide insight into Alzheimer disease pathogenesis.

PMID- 7568160
TI  - Tertiary structure of an amyloid immunoglobulin light chain protein: a proposed
      model for amyloid fibril formation.
AB  - An immunoglobulin light chain protein was isolated from the urine of an
      individual (BRE) with systemic amyloidosis. Complete amino acid sequence of the
      variable region of the light chain (VL) protein established it as a kappa I,
      which when compared with other kappa I amyloid associated proteins had unique
      residues, including Ile-34, Leu-40, and Tyr-71. To study the tertiary structure,
      BRE VL was expressed in Escherichia coli by using a PCR product amplified from
      the patient BRE's bone marrow DNA. The PCR product was ligated into pCZ11, a
      thermal-inducible replication vector. Recombinant BRE VL was isolated, purified
      to homogeneity, and crystallized by using ammonium sulfate as the precipitant.
      Two crystal forms were obtained. In crystal form I the BRE VL kappa domain
      crystallizes as a dimer with unit cell constants isomorphous to previously
      published kappa protein structures. Comparison with a nonamyloid VL kappa domain
      from patient REI, identified significant differences in position of residues in
      the hypervariable segments plus variations in framework region (FR) segments 40
      46 (FR2) and 66-67 (FR3). In addition, positional differences can be seen along
      the two types of local diads, corresponding to the monomer-monomer and dimer
      dimer interfaces. From the packing diagram, a model for the amyloid light chain
      (AL) fibril is proposed based on a pseudohexagonal spiral structure with a rise
      of approximately the width of two dimers per 360 degree turn. This spiral
      structure could be consistent with the dimensions of amyloid fibrils as
      determined by electron microscopy.

PMID- 7568161
TI  - A nerve growth factor peptide retards seizure development and inhibits neuronal
      sprouting in a rat model of epilepsy.
AB  - Kindling, an animal model of epilepsy wherein seizures are induced by subcortical
      electrical stimulation, results in the upregulation of neurotrophin mRNA and
      protein in the adult rat forebrain and causes mossy fiber sprouting in the
      hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve
      growth factor domain that interferes with the binding of neurotrophins to their
      receptors resulted in significant retardation of kindling and inhibition of mossy
      fiber sprouting. These findings suggest a critical role for neurotrophins in both
      kindling and kindling-induced synaptic reorganization.

PMID- 7568163
TI  - Localization of pheromonal sexual dimorphism in Drosophila melanogaster and its
      effect on sexual isolation.
AB  - Drosophila melanogaster is sexually dimorphic for cuticular hydrocarbons, with
      males and females having strikingly different profiles of the long-chain
      compounds that act as contact pheromones. Gas-chromatographic analysis of sexual
      mosaics reveals that the sex specificity of hydrocarbons is located in the
      abdomen. This explains previous observations that D. melanogaster males display
      the strongest courtship toward mosaics with female abdomens. We also show that
      males of the sibling species Drosophila simulans preferentially court D.
      melanogaster mosaics with male abdomens. Because the primary male hydrocarbon in
      D. melanogaster is also the primary female hydrocarbon in D. simulans, this
      supports the idea that interspecific differences in cuticular hydrocarbons
      contribute to sexual isolation.

PMID- 7568164
TI  - Major histocompatibility complex binding affinity of an antigenic determinant is
      crucial for the differential secretion of interleukin 4/5 or interferon gamma by
      T cells.
AB  - Differential activation of CD4+ T-cell precursors in vivo leads to the
      development of effectors with unique patterns of lymphokine secretion. To
      investigate whether the differential pattern of lymphokine secretion is
      influenced by factors associated with either the display and/or recognition of
      the ligand, we have used a set of ligands with various class II binding
      affinities but unchanged T-cell specificity. The ligand that exhibited
      approximately 10,000-fold higher binding to I-Au considerably increased the
      frequency of interferon gamma-producing but not interleukin (IL) 4- or IL-5
      secreting cells in vivo. Using an established ligand-specific, CD4+ T-cell clone
      secreting only IL-4, we also demonstrated that stimulation with the highest
      affinity ligand resulted in interferon gamma production in vitro. In contrast,
      ligands that demonstrated relatively lower class II binding induced only IL-4
      secretion. These data suggest that the major histocompatibility complex binding
      affinity of antigenic determinants, leading to differential interactions at the T
      cell-antigen-presenting cell interface, can be crucial for the differential
      development of cytokine patterns in T cells.

PMID- 7568165
TI  - G protein activation kinetics and spillover of gamma-aminobutyric acid may
      account for differences between inhibitory responses in the hippocampus and
      thalamus.
AB  - We have developed a model of gamma-aminobutyric acid (GABA)ergic synaptic
      transmission mediated by GABAA and GABAB receptors, including cooperativity in
      the guanine nucleotide binding protein (G protein) cascade mediating the
      activation of K+ channels by GABAB receptors. If the binding of several G
      proteins is needed to activate the K+ channels, then only a prolonged activation
      of GABAB receptors evoked detectable currents. This could occur if strong stimuli
      evoked release in adjacent terminals and the spillover resulted in prolonged
      activation of the receptors, leading to inhibitory responses similar to those
      observed in hippocampal slices. The same model also reproduced thalamic GABAB
      responses to high-frequency bursts of stimuli. In this case, prolonged activation
      of the receptors was due to high-frequency release conditions. This model
      provides insights into the function of GABAB receptors in normal and epileptic
      discharges.

PMID- 7568162
TI  - Platelet-derived growth factor induces apoptosis in growth-arrested murine
      fibroblasts.
AB  - The platelet-derived growth factor (PDGF) is a potent mitogen for murine
      fibroblasts. PDGF-stimulated cells express a set of immediate-early-response
      genes but require additional (progression) factors in serum to progress through
      the cell cycle. Serum-deprived cells are reversibly arrested in G0 phase and fail
      to fully traverse the G1 phase of the cell cycle when stimulated by PDGF alone.
      We now report that serum-deprived normal rat kidney fibroblast (NRK) cells
      stimulated by either PDGF AA or PDGF BB homodimers undergo apoptotic cell death.
      Furthermore, we show that epidermal growth factor also induces apoptotic cell
      death in serum-deprived NRK cells, epidermal growth factor enhances the rate of
      apoptosis in PDGF-treated cells, and a progression factor (insulin) but not
      endogenously expressed Bc1-2 fully protects NRK cells from PDGF-stimulated
      apoptosis. The results indicate that PDGF induces apoptosis in growth-arrested
      NRK cells and that the inability of NRK cells to transit the G1/S checkpoint is
      the critical determinant in establishing the genetic program(s) to direct the
      PDGF signal to apoptosis. The results suggest that polypeptide growth factors in
      vivo may signal cell fate positively or negatively in settings that limit the
      potential of cells to completely transit the cell cycle.

PMID- 7568166
TI  - Sensitivity to abscisic acid of guard-cell K+ channels is suppressed by abi1-1, a
      mutant Arabidopsis gene encoding a putative protein phosphatase.
AB  - Abscisic acid (ABA) modulates the activities of three major classes of ion
      channels--inward- and outward-rectifying K+ channels (IK,in and IK,out,
      respectively) and anion channels--at the guard-cell plasma membrane to achieve a
      net efflux of osmotica and stomatal closure. Disruption of ABA sensitivity in
      wilty abi1-1 mutants of Arabidopsis and evidence that this gene encodes a protein
      phosphatase suggest that protein (de)-phosphorylation contributes to guard-cell
      transport control by ABA. To pinpoint the role of ABI1, the abi1-1 dominant
      mutant allele was stably transformed into Nicotiana benthamiana and its influence
      on IK,in, IK,out, and the anion channels was monitored in guard cells under
      voltage clamp. Compared with guard cells from wild-type and vector-transformed
      control plants, expression of the abi1-1 gene was associated with 2- to 6-fold
      reductions in IK,out and an insensitivity of both IK,in and IK,out to 20 microM
      ABA. In contrast, no differences between control and abi1-1 transgenic plants
      were observed in the anion current or its response to ABA. Parallel measurements
      of intracellular pH (pHi) using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5
      (and -6)-carboxyfluorescein (BCECF) in every case showed a 0.15- to 0.2-pH-unit
      alkalinization in ABA, demonstrating that the transgene was without effect on the
      pHi signal that mediates in ABA-evoked K+ channel control. In guard cells from
      the abi1-1 transformants, normal sensitivity of both K+ channels to and stomatal
      closure in ABA was recovered in the presence of 100 microM H7 and 0.5 microM
      staurosporine, both broad-range protein kinase antagonists. These results
      demonstrate an aberrant K+ channel behavior--including channel insensitivity to
      ABA-dependent alkalinization of pHi--as a major consequence of abi1-1 action and
      implicate AB11 as part of a phosphatase/kinase pathway that modulates the
      sensitivity of guard-cell K+ channels to ABA-evoked signal cascades.

PMID- 7568168
TI  - A protein-binding domain, EH, identified in the receptor tyrosine kinase
      substrate Eps15 and conserved in evolution.
AB  - In this report we structurally and functionally define a binding domain that is
      involved in protein association and that we have designated EH (for Eps15
      homology domain). This domain was identified in the tyrosine kinase substrate
      Eps15 on the basis of regional conservation with several heterogeneous proteins
      of yeast and nematode. The EH domain spans about 70 amino acids and shows
      approximately 60% overall amino acid conservation. We demonstrated the ability of
      the EH domain to specifically bind cytosolic proteins in normal and malignant
      cells of mesenchymal, epithelial, and hematopoietic origin. These observations
      prompted our search for additional EH-containing proteins in mammalian cells.
      Using an EH domain-specific probe derived from the eps15 cDNA, we cloned and
      characterized a cDNA encoding an EH-containing protein with overall similarity to
      Eps15; we designated this protein Eps15r (for Eps15-related). Structural
      comparison of Eps15 and Eps15r defines a family of signal transducers possessing
      extensive networking abilities including EH-mediated binding and association with
      Src homology 3-containing proteins.

PMID- 7568167
TI  - A nuclear hormone receptor-associated protein that inhibits transactivation by
      the thyroid hormone and retinoic acid receptors.
AB  - Nuclear hormone receptors are transcription factors that require multiple protein
      protein interactions to regulate the expression of their target genes. Using the
      yeast two-hybrid system, we identified a protein, thyroid hormone receptor
      uncoupling protein (TRUP), that specifically interacts with a region of the human
      thyroid hormone receptor (TR) consisting of the hinge region and the N-terminal
      portion of the ligand binding domain in a hormone-independent manner.
      Interestingly, TRUP inhibits transactivation by TR and the retinoic acid receptor
      but has no effect on the estrogen receptor or the retinoid X receptor in
      mammalian cells. We also demonstrate that TRUP exerts its action on TR and
      retinoic acid receptor by interfering with their abilities to interact with their
      DNA. TRUP represents a type of regulatory protein that modulates the
      transcriptional activity of a subclass of the nuclear hormone receptor
      superfamily by preventing interaction with their genomic response elements.

PMID- 7568169
TI  - Signaling by ABL oncogenes through cyclin D1.
AB  - Oncogenic signals induce cellular proliferation by deregulating the cell division
      cycle. Cyclin D1, a regulator of G1-phase progression, acts synergistically with
      ABL oncogenes in transforming fibroblasts and hematopoietic cells in culture.
      Synergy with v-Abl depended on a motif in cyclin D1 that mediates its binding to
      the retinoblastoma protein, suggesting that ABL oncogenes in part mediate their
      mitogenic effects via a retinoblastoma protein-dependent pathway. Overexpression
      of cyclin D1, but not cyclin E, rescued a signaling-defective src-homology 2
      (SH2) domain mutant of BCR-ABL for transformation of cells in culture and
      malignant tumor formation in vivo. These results demonstrate that cyclin D1 can
      provide essential signals for malignant transformation in concert with an
      activated tyrosine kinase.

PMID- 7568170
TI  - Proximity of the manganese cluster of photosystem II to the redox-active tyrosine
      YZ.
AB  - Electron spin echo electron-nuclear double resonance (ESE-ENDOR) experiments
      performed on a broad radical electron paramagnetic resonance (EPR) signal
      observed in photosystem II particles depleted of Ca2+ indicate that this signal
      arises from the redox-active tyrosine YZ. The tyrosine EPR signal width is
      increased relative to that observed in a manganese-depleted preparation due to a
      magnetic interaction between the photosystem II manganese cluster and the
      tyrosine radical. The manganese cluster is located asymmetrically with respect to
      the symmetry-related tyrosines YZ and YD. The distance between the YZ tyrosine
      and the manganese cluster is estimated to be approximately 4.5 A. Due to this
      close proximity of the Mn cluster and the redox-active tyrosine YZ, we propose
      that this tyrosine abstracts protons from substrate water bound to the Mn
      cluster.

PMID- 7568171
TI  - Testis/brain RNA-binding protein attaches translationally repressed and
      transported mRNAs to microtubules.
AB  - We have previously identified a testicular phosphoprotein that binds to highly
      conserved sequences (Y and H elements) in the 3' untranslated regions (UTRs) of
      testicular mRNAs and suppresses in vitro translation of mRNA constructs that
      contain these sequences. This protein, testis/brain RNA-binding protein (TB-RBP)
      also is abundant in brain and binds to brain mRNAs whose 3' UTRs contain similar
      sequences. Here we show that TB-RBP binds specific mRNAs to microtubules (MTs) in
      vitro. When TB-RBP is added to MTs reassembled from either crude brain extracts
      or from purified tubulin, most of the TB-RBP binds to MTs. The association of TB
      RBP with MTs requires the assembly of MTs and is diminished by colcemid,
      cytochalasin D, and high levels of salt. Transcripts from the 3' UTRs of three
      mRNAs that contain the conserved sequence elements (transcripts for protamine 2,
      tau protein, and myelin basic protein) are linked by TB-RBP to MTs, whereas
      transcripts that lack the conserved sequences do not bind TB-RBP. We conclude
      that TB-RBP serves as an attachment protein for the MT association of specific
      mRNAs. Considering its ability to arrest translation in vitro, we propose that TB
      RBP functions in the storage and transportation of mRNAs to specific
      intracellular sites where they are translated.

PMID- 7568172
TI  - Survival of mouse pancreatic islet allografts in recipients treated with
      allogeneic small lymphocytes and antibody to CD40 ligand.
AB  - Combined treatment with allogeneic small lymphocytes or T-depleted small
      lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitted indefinite
      pancreatic islet allograft survival in 37 of 40 recipients that differed from
      islet donors at major and minor histocompatibility loci. The effect of the
      allogeneic small lymphocytes was donor antigen-specific. Neither treatment alone
      was as effective as combined treatment, although anti-CD40L by itself allowed
      indefinite islet allograft survival in 40% of recipients. Our interpretation is
      that small lymphocytes expressing donor antigens in the absence of appropriate
      costimulatory signals are tolerogenic for alloreactive host cells. Anti-CD40L
      antibody may prevent host T cells from inducing costimulatory signals in donor
      lymphocytes or islet grafts.

PMID- 7568173
TI  - Hematopoietic and lung abnormalities in mice with a null mutation of the common
      beta subunit of the receptors for granulocyte-macrophage colony-stimulating
      factor and interleukins 3 and 5.
AB  - Gene targeting was used to create mice with a null mutation of the gene encoding
      the common beta subunit (beta C) of the granulocyte-macrophage colony-stimulating
      factor (GM-CSF), interleukin 3 (IL-3; multi-CSF), and interleukin 5 (IL-5)
      receptor complexes (beta C-/- mice). High-affinity binding of GM-CSF was
      abolished in beta C-/- bone marrow cells, while cells from heterozygous animals
      (beta C+/- mice) showed an intermediate number of high-affinity receptors.
      Binding of IL-3 was unaffected, confirming that the IL-3-specific beta chain
      remained intact. Eosinophil numbers in peripheral blood and bone marrow of beta C
      /- animals were reduced, while other hematological parameters were normal. In
      clonal cultures of beta C-/- bone marrow cells, even high concentrations of GM
      CSF and IL-5 failed to stimulate colony formation, but the cells exhibited normal
      quantitative responsiveness to stimulation by IL-3 and other growth factors. beta
      C-/- mice exhibited normal development and survived to young adult life, although
      they developed pulmonary peribronchovascular lymphoid infiltrates and areas
      resembling alveolar proteinosis. There was no detectable difference in the
      systemic clearance and distribution of GM-CSF between beta C-/- and wild-type
      littermates. The data establish that beta C is normally limiting for high
      affinity binding of GM-CSF and demonstrate that systemic clearance of GM-CSF is
      not mediated via such high-affinity receptor complexes.

PMID- 7568174
TI  - A histologically distinctive interstitial pneumonia induced by overexpression of
      the interleukin 6, transforming growth factor beta 1, or platelet-derived growth
      factor B gene.
AB  - Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of
      the interstitium. To determine the relevance of humoral factors in the
      pathogenesis of interstitial pneumonia, we introduced expression vectors into
      Wistar rats via the trachea to locally overexpress humoral factors in the lungs.
      Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis
      without marked fibroblast proliferation. In contrast, overexpression of human
      transforming growth factor beta 1 or human platelet-derived growth factor B gene
      induced only mild or apparent cellular infiltration in the alveoli, respectively.
      However, both factors induced significant proliferation of fibroblasts and
      deposition of collagen fibrils. These histopathologic changes induced by the
      transforming growth factor beta 1 and platelet-derived growth factor B gene are
      partly akin to those changes seen in lung tissues from patients with pulmonary
      fibrosis and markedly contrast with the changes induced by overexpression of the
      IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

PMID- 7568175
TI  - Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2
      independent regulator of apoptosis in human B-lineage lymphoma cells.
AB  - CD19 receptor is expressed at high levels on human B-lineage lymphoid cells and
      is physically associated with the Src protooncogene family protein-tyrosine
      kinase Lyn. Recent studies indicate that the membrane-associated CD19-Lyn
      receptor-enzyme complex plays a pivotal role for survival and clonogenicity of
      immature B-cell precursors from acute lymphoblastic leukemia patients, but its
      significance for mature B-lineage lymphoid cells (e.g., B-lineage lymphoma cells)
      is unknown. CD19-associated Lyn kinase can be selectively targeted and inhibited
      with B43-Gen, a CD19 receptor-specific immunoconjugate containing the naturally
      occurring protein-tyrosine kinase inhibitor genistein (Gen). We now present
      experimental evidence that targeting the membrane-associated CD19-Lyn complex in
      vitro with B43-Gen triggers rapid apoptotic cell death in highly radiation
      resistant p53-Bax- Ramos-BT B-lineage lymphoma cells expressing high levels of
      Bcl-2 protein without affecting the Bcl-2 expression level. The therapeutic
      potential of this membrane-directed apoptosis induction strategy was examined in
      a scid mouse xenograft model of radiation-resistant high-grade human B-lineage
      lymphoma. Remarkably, in vivo treatment of scid mice challenged with an
      invariably fatal number of Ramos-BT cells with B43-Gen at a dose level < 1/10 the
      maximum tolerated dose resulted in 70% long-term event-free survival. Taken
      together, these results provide unprecedented evidence that the membrane
      associated anti-apoptotic CD19-Lyn complex may be at least as important as Bcl
      2/Bax ratio for survival of lymphoma cells.

PMID- 7568176
TI  - The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low
      density lipoprotein and phosphatidylserine-rich liposomes is identical to
      macrosialin, the mouse homologue of human CD68.
AB  - We have previously reported the partial purification of a 94- to 97-kDa plasma
      membrane protein from mouse peritoneal macrophages that binds oxidatively
      modified low density lipoprotein (OxLDL) and phosphatidylserine-rich liposomes.
      We have now identified that protein as macrosialin, a previously cloned
      macrophage-restricted membrane protein in the lysosomal-associated membrane
      protein family (mouse homologue of human CD68). Early in the course of
      purification of the 94- to 97-kDa protein, a new OxLDL-binding band at 190-200
      kDa appeared and copurified with the 94- to 97-kDa protein. The HPLC pattern of
      tryptic peptides from this higher molecular mass ligand-binding band closely
      matched that derived from the 94- to 97-kDa band. Specifically, the same three
      macrosialin-derived tryptic peptides (9, 9, and 15 residues) were present in the
      purified 94- to 97-kDa band and in the 190- to 200-kDa band and antisera raised
      against peptide sequences in macrosialin recognized both bands. An antiserum
      against macrosialin precipitated most of the 94- to 97-kDa OxLDL-binding
      material. We conclude that the binding of OxLDL to mouse macrophage membranes is
      in part attributable to macrosialin. Our previous studies show that OxLDL
      competes with oxidized red blood cells and with apoptotic thymocytes for binding
      to mouse peritoneal macrophages. Whether macrosialin plays a role in recognition
      of OxLDL and oxidatively damaged cells by intact macrophages remains uncertain.

PMID- 7568178
TI  - Drug delivery: piercing vesicles by their adsorption onto a porous medium.
AB  - Experimental evidence is presented that supports the possibility of building a
      "molecular drill." By the adsorption of a vesicle onto a porous substrate
      (specifically, a lycopode grain), it was possible to increase the permeability of
      the vesicle by locally stretching its membrane. Molecules contained within the
      vesicle, which could not cross the membrane, were delivered to the porous
      substrate upon adsorption. This general process could provide another method for
      drug delivery and targeting.

PMID- 7568177
TI  - Association of erythroid transcription factors: complexes involving the LIM
      protein RBTN2 and the zinc-finger protein GATA1.
AB  - The RBTN2 LIM-domain protein, originally identified as an oncogenic protein in
      human T-cell leukemia, is essential for erythropoiesis. A possible role for RBTN2
      in transcription during erythropoiesis has been investigated. Direct interaction
      of the RBTN2 protein was observed in vivo and in vitro with the GATA1 or -2 zinc
      finger transcription factors, as well as with the basic helix-loop-helix protein
      TAL1. By using mammalian two-hybrid analysis, complexes involving RBTN2, TAL1,
      and GATA1, together with E47, the basic helix-loop-helix heterodimerization
      partner of TAL1, could be demonstrated. Thus, a molecular link exists between
      three proteins crucial for erythropoiesis, and the data suggest that variations
      in amounts of complexes involving RBTN2, TAL1, and GATA1 could be important for
      erythroid differentiation.

PMID- 7568179
TI  - min K channels form by assembly of at least 14 subunits.
AB  - Injection of min K mRNA into Xenopus oocytes results in expression of slowly
      activating voltage-dependent potassium channels, distinct from those induced by
      expression of other cloned potassium channels. The min K protein also differs in
      structure, containing only a single predicted transmembrane domain. While it has
      been demonstrated that all other cloned potassium channels form by association of
      four independent subunits, the number of min K monomers which constitute a
      functional channel is unknown. In rat min K, replacement of Ser-69 by Ala (S69A)
      causes a shift in the current-voltage (I-V) relationship to more depolarized
      potentials; currents are not observed at potentials negative to 0 mV. To
      determine the subunit stoichiometry of min K channels, wild-type and S69A
      subunits were coexpressed. Injections of a constant amount of wild-type mRNA with
      increasing amounts of S69A mRNA led to potassium currents of decreasing amplitude
      upon voltage commands to -20 mV. Applying a binomial distribution to the
      reduction of current amplitudes as a function of the different coinjection
      mixtures yielded a subunit stoichiometry of at least 14 monomers for each
      functional min K channel. A model is presented for how min K subunits may form a
      channel.

PMID- 7568180
TI  - Intracellular coexistence of methano- and thioautotrophic bacteria in a
      hydrothermal vent mussel.
AB  - The coexistence of two phylogenetically distinct symbiont species within a single
      cell, a condition not previously known in any metazoan, is demonstrated in the
      gills of a Mid-Atlantic Ridge hydrothermal vent mussel (family Mytilidae). Large
      and small symbiont morphotypes within the gill bacteriocytes are shown to be
      separate bacterial species by molecular phylogenetic analysis and fluorescent in
      situ hybridization. The two symbiont species are affiliated with thioautotrophic
      and methanotrophic symbionts previously found in monospecific associations with
      closely related mytilids from deep-sea hydrothermal vents and hydrocarbon seeps.

PMID- 7568182
TI  - Detection of exocytosis at individual pancreatic beta cells by amperometry at a
      chemically modified microelectrode.
AB  - Amperometry at a carbon fiber microelectrode modified with a composite of
      ruthenium oxide and cyanoruthenate was used to monitor chemical secretions of
      single pancreatic beta cells from rats and humans. When the insulin secretagogues
      glucose, tolbutamide, and K+ were applied to the cell, a series of randomly
      occurring current spikes was observed. The current spikes were shown to be due to
      the detection of chemical substances secreted from the cell. Chromatography
      showed that the primary secreted substance detected by the electrode was insulin.
      The current spikes were strongly dependent on external Ca2+, had an average area
      that was independent of the stimulation method, and had an area distribution
      which corresponded to the distribution of vesicle sizes in beta cells. It was
      concluded that the spikes were due to the detection of concentration pulses of
      insulin secreted by exocytosis.

PMID- 7568181
TI  - Expression of lactoferrin receptors is increased in the mesencephalon of patients
      with Parkinson disease.
AB  - The degeneration of nigral dopaminergic neurons in Parkinson disease is believed
      to be associated with oxidative stress. Since iron levels are increased in the
      substantia nigra of parkinsonian patients and this metal catalyzes the formation
      of free radicals, it may be involved in the mechanisms of nerve cell death. The
      cause of nigral iron increase is not understood. Iron acquisition by neurons may
      occur from iron-transferrin complexes with a direct interaction with specific
      membrane receptors, but recent results have shown a low density of transferrin
      receptors in the substantia nigra. To investigate whether neuronal death in
      Parkinson disease may be associated with changes in a pathway supplementary to
      that of transferrin, lactoferrin (lactotransferrin) receptor expression was
      studied in the mesencephalon. In this report we present evidence from
      immunohistochemical staining of postmortem human brain tissue that lactoferrin
      receptors are localized on neurons (perikarya, dendrites, axons), cerebral
      microvasculature, and, in some cases, glial cells. In parkinsonian patients,
      lactoferrin receptor immunoreactivity on neurons and microvessels was increased
      and more pronounced in those regions of the mesencephalon where the loss of
      dopaminergic neurons is severe. Moreover, in the substantia nigra, the intensity
      of immunoreactivity on neurons and microvessels was higher for patients with
      higher nigral dopaminergic loss. These data suggest that lactoferrin receptors on
      vulnerable neurons may increase intraneuronal iron levels and contribute to the
      degeneration of nigral dopaminergic neurons in Parkinson disease.

PMID- 7568183
TI  - rSec6 and rSec8, mammalian homologs of yeast proteins essential for secretion.
AB  - Many of the molecules necessary for neurotransmission are homologous to proteins
      involved in the Golgi-to-plasma membrane stage of the yeast secretory pathway. Of
      15 genes known to be essential for the later stages of vesicle trafficking in
      yeast, 7 have no identified mammalian homologs. These include the yeast SEC6,
      SEC8, and SEC15 genes, whose products are constituents of a 19.5S particle that
      interacts with the GTP-binding protein Sec4p. Here we report the sequences of
      rSec6 and rSec8, rat homologs of Sec6p and Sec8p. The rSec6 cDNA is predicted to
      encode an 87-kDa protein with 22% amino acid identity to Sec6p, and the rSec8
      cDNA is predicted to encode a 110-kDa protein which is 20% identical to Sec8p.
      Northern blot analysis indicates that rSec6 and rSec8 are expressed in similar
      tissues. Immunodetection reveals that rSec8 is part of a soluble 17S particle in
      brain. COS cell cotransfection studies demonstrate that rSec8 colocalizes with
      the GTP-binding protein Rab3a and syntaxin 1a, two proteins involved in synaptic
      vesicle docking and fusion at the presynaptic terminal. These data suggest that
      rSec8 is a component of a high molecular weight complex which may participate in
      the regulation of vesicle docking and fusion in brain.

PMID- 7568184
TI  - Stimulation of ionotropic glutamate receptors activates transcription factor NF
      kappa B in primary neurons.
AB  - L-Glutamate is the most common excitatory neurotransmitter in the brain and plays
      a crucial role in neuronal plasticity as well as in neurotoxicity. While a large
      body of literature describes the induction of immediate-early genes, including c
      fos, fosB, c-jun, junB, zif/268, and krox genes by glutamate and agonists in
      neurons, very little is known about preexisting transcription factors controlling
      the induction of such genes. This prompted us to investigate whether stimulation
      of glutamate receptors can activate NF-kappa B, which is present in neurons in
      either inducible or constitutive form. Here we report that brief treatments with
      kainate or high potassium strongly activated NF-kappa B in granule cells from rat
      cerebellum. This was detected at the single cell level by immunostaining with a
      monoclonal antibody that selectively reacts with the transcriptionally active,
      nuclear form of NF-kappa B p65. The activation of NF-kappa B could be blocked
      with the antioxidant pyrrolidine dithiocarbamate, suggesting the involvement of
      reactive oxygen intermediates. The data may explain the kainate-induced cell
      surface expression of major histocompatibility complex class I molecules, which
      are encoded by genes known to be controlled by NF-kappa B. Moreover, NF-kappa B
      activity was found to change dramatically in neurons during development of the
      cerebellum between days 5 and 7 after birth.

PMID- 7568188
TI  - Identification of a 95-kDa WEE1-like tyrosine kinase in HeLa cells.
AB  - Human WEE1 (WEE1Hu) was cloned on the basis of its ability to rescue wee1+
      mutants in fission yeast [Igarashi, M., Nagata, A., Jinno, S., Suto, K. &
      Okayama, H. (1991) Nature (London) 353, 80-83]. Biochemical studies carried out
      in vitro with recombinant protein demonstrated that WEE1Hu encodes a tyrosine
      kinase of approximately 49 kDa that phosphorylates p34cdc2 on Tyr-15 [Parker, L.
      L. & Piwnica-Worms, H. (1992) Science 257, 1955-1957]. To study the regulation of
      WEE1Hu in human cells, two polyclonal antibodies to bacterially produced
      p49WEE1Hu were generated. In addition, a peptide antibody generated against amino
      acids 361-388 of p49WEE1Hu was also used. Unexpectantly, these antibodies
      recognized a protein with an apparent molecular mass of 95 kDa in HeLa cells,
      rather than one of 49 kDa. Immunoprecipitates of p95 phosphorylated p34cdc2 on
      Tyr-15, indicating that p95 is functionally related to p49WEEIHu, and mapping
      studies demonstrated that p95 is structurally related to p49WEE1Hu. In addition,
      the substrate specificity of p95 was more similar to that of fission yeast
      p107wee1 than to that of human p49WEE1. Finally, the kinase activity of p95
      toward p34cdc2/cyclin B was severely impaired during mitosis. Taken together,
      these results indicate that the original WEE1Hu clone isolated in genetic screens
      encodes only the catalytic domain of human WEE1 and that the authentic human WEE1
      protein has an apparent molecular mass of approximately 95 kDa.

PMID- 7568186
TI  - A model for the transcriptional regulation of the CYP2B1/B2 gene in rat liver.
AB  - The phenobarbitone-responsive minimal promoter has been shown to lie between nt 
      179 and nt + 1 in the 5' (upstream) region of the CYP2B1/B2 gene in rat liver, on
      the basis of the drug responsiveness of the sequence linked to human growth
      hormone gene as reporter and targeted to liver as an asialoglycoprotein-DNA
      complex in vivo. Competition analyses of the nuclear protein-DNA complexes formed
      in gel shift assays with the positive (nt -69 to -98) and negative (nt -126 to 
      160) cis elements (PE and NE, respectively) identified within this region earlier
      indicate that the same protein may be binding to both the elements. The protein
      species purified on PE and NE affinity columns appear to be identical based on
      SDS/PAGE analysis, where it migrates as a protein of 26-28 kDa. Traces of a high
      molecular weight protein (94-100 kDa) are also seen in the preparation obtained
      after one round of affinity chromatography. The purified protein stimulates
      transcription of a minigene construct containing the 179 nt on the 5' side of the
      CYP2B1/B2 gene linked to the I exon in a cell-free system from liver nuclei. The
      purified protein can give rise to all the three complexes (I, II, and III) with
      the PE, just as the crude nuclear extract, under appropriate conditions.
      Manipulations in vitro indicate that the NE has a significantly higher affinity
      for the dephosphorylated form than for the phosphorylated form of the protein.
      The PE binds both forms. Phenobarbitone treatment of the animal leads to a
      significant increase in the phosphorylation of the 26- to 28-kDa and 94-kDa
      proteins in nuclear labeling experiments followed by isolation on a PE affinity
      column. We propose that the protein binding predominantly to the NE in the
      dephosphorylated state characterizes the basal level of transcription of the
      CYP2B1/B2 gene. Phenobarbitone treatment leads to phosphorylation of the protein,
      shifting the equilibrium toward binding to the PE. This can promote interaction
      with an upstream enhancer through other proteins such as the 94-kDa protein and
      leads to a significant activation of transcription.

PMID- 7568185
TI  - Transcription factor GATA-1 permits survival and maturation of erythroid
      precursors by preventing apoptosis.
AB  - The transcription factor GATA-1 recognizes a consensus motif present in
      regulatory regions of numerous erythroid-expressed genes. Mouse embryonic stem
      cells lacking GATA-1 cannot form mature red blood cells in vivo. In vitro
      differentiation of GATA-1- embryonic stem cells gives rise to a population of
      committed erythroid precursors that exhibit developmental arrest and death. We
      show here that the demise of GATA-1- erythroid cells is accompanied by several
      features characteristics of apoptosis. This process occurs despite normal
      expression of all known GATA target genes examined, including the erythropoietin
      receptor, and independent of detectable accumulation of the tumor suppressor
      protein p53. Thus, in addition to its established role in regulating genes that
      define the erythroid phenotype, GATA-1 also supports the viability of red cell
      precursors by suppressing apoptosis. These results illustrate the multifunctional
      nature of GATA-1 and suggest a mechanism by which other hematopoietic
      transcription factors may ensure the development of specific lineages.

PMID- 7568187
TI  - Thyroid-stimulating hormone (TSH)-directed induction of the CREM gene in the
      thyroid gland participates in the long-term desensitization of the TSH receptor.
AB  - Thyroid gland function is regulated by the hypothalamic-pituitary axis via the
      secretion of TSH, according to environmental, developmental, and circadian
      stimuli. TSH modulates both the secretion of thyroid hormone and gland trophism
      through interaction with a specific guanine nucleotide-binding protein-coupled
      receptor (TSH receptor; TSH-R), which elicits the activation of the cAMP
      dependent signaling pathway. After TSH stimulation, the levels of TSH-R RNA are
      known to decrease dramatically within a few hours. This phenomenon ultimately
      leads to homologous long-term desensitization of the TSH-R. Here we show that TSH
      drives the induction of the inducible cAMP early repressor (ICER) isoform of the
      cAMP response element (CRE) modulator gene both in rat thyroid gland and in the
      differentiated thyroid cell line FRTL-5. The kinetics of ICER protein induction
      mirrors the down-regulation of TSH-R mRNA. ICER binds to a CRE-like sequence in
      the TSH-R promoter and represses its expression. Thus, ICER induction by TSH in
      the thyroid gland represents a paradigm of the molecular mechanism by which
      pituitary hormones elicit homologous long-term desensitization.

PMID- 7568189
TI  - BiP and Sec63p are required for both co- and posttranslational protein
      translocation into the yeast endoplasmic reticulum.
AB  - Two interacting heat shock cognate proteins in the lumen of the yeast endoplasmic
      reticulum (ER), Sec63p and BiP (Kar2p), are required for posttranslational
      translocation of yeast alpha-factor precursor in vitro. To investigate the role
      of these proteins in cotranslational translocation, we examined the import of
      invertase into wild-type, sec63, and kar2 mutant yeast membranes. We found that
      Sec63p and Kar2p are necessary for both co- and posttranslational translocation
      in yeast. Several kar2 mutants, one of which had normal ATPase activity, were
      defective in cotranslational translocation of invertase. We conclude that the
      requirement for BiP/Kar2p, which is not seen in a reaction reconstituted with
      pure mammalian membrane proteins [Gorlich, D. & Rapoport, T.A. (1993) Cell 75,
      615-630], is not due to a distinction between cotranslational translocation in
      mammalian cells and posttranslational translocation in yeast cells.

PMID- 7568190
TI  - The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement of
      transplanted murine hemopoietic progenitors between bone marrow and spleen.
AB  - Selective lodgement or homing of transplanted hemopoietic stem cells in the
      recipient's bone marrow (BM) is a critical step in the establishment of long-term
      hemopoiesis after BM transplantation. However, despite its biologic and clinical
      significance, little is understood about the process of homing. In the present
      study, we have concentrated on the initial stages of homing and explored the
      functional role in vivo of some of the adhesion pathways previously found to
      mediate in vitro adhesion of hemopoietic cells to cultured BM stroma. We have
      found that homing of murine hemopoietic progenitors of the BM of lethally
      irradiated recipients at 3 h after transplant was significantly reduced after
      pretreatment of the donor cells with an antibody to the integrin very late
      antigen 4 (VLA4). This inhibition of marrow homing was accompanied by an increase
      in hemopoietic progenitors circulating in the blood and an increased uptake of
      these progenitors by the spleen. Similar results were obtained by treatment of
      the recipients with an antibody to vascular cell adhesion molecule 1 (VCAM-1), a
      ligand for VLA4. Furthermore, we showed that administration of the same
      antibodies (anti-VLA4 or anti-VCAM-1) to normal animals causes mobilization of
      hemopoietic progenitors into blood. These data suggest that hemopoietic cell
      lodgement in the BM is a regulatable process and can be influenced by VLA4/VCAM-1
      adhesion pathway. Although additional molecular pathways are not excluded and may
      be likely, our data establish VCAM-1 as a BM endothelial addressin, analogous to
      the role that mucosal addressin cell adhesion molecule (MAdCAM) plays in
      lymphocyte homing. Whether splenic uptake of hemopoietic progenitors is passive
      or controlled through different mechanisms remains to be clarified. In addition,
      we provide experimental evidence that homing and mobilization are related
      phenomena involving, at least partly, similar molecular pathways.

PMID- 7568191
TI  - TRPC1, a human homolog of a Drosophila store-operated channel.
AB  - In many vertebrate and invertebrate cells, inositol 1,4,5-trisphospate production
      induces a biphasic Ca2+ signal. Mobilization of Ca2+ from internal stores drives
      the initial burst. The second phase, referred to as store-operated Ca2+ entry
      (formerly capacitative Ca2+ entry), occurs when depletion of intracellular Ca2+
      pools activates a non-voltage-sensitive plasma membrane Ca2+ conductance. Despite
      the prevalence of store-operated Ca2+ entry, no vertebrate channel responsible
      for store-operated Ca2+ entry has been reported. trp (transient receptor
      potential), a Drosophila gene required in phototransduction, encodes the only
      known candidate for such a channel throughout phylogeny. In this report, we
      describe the molecular characterization of a human homolog of trp, TRPC1. TRPC1
      (transient receptor potential channel-related protein 1) was 40% identical to
      Drosophila TRP over most of the protein and lacked the charged residues in the S4
      transmembrane region proposed to be required for the voltage sensor in many
      voltage-gated ion channels. TRPC1 was expressed at the highest levels in the
      fetal brain and in the adult heart, brain, testis, and ovaries. Evidence is also
      presented that TRPC1 represents the archetype of a family of related human
      proteins.

PMID- 7568192
TI  - Protein evolution on partially correlated landscapes.
AB  - We extend an earlier model of protein evolution on a rugged landscape to the case
      in which the landscape exhibits a variable degree of correlation (i.e.,
      smoothness). Correlation is introduced by assuming that a protein is composed of
      a set of independent blocks or domains and that mutation in one block affects the
      contribution of that block alone to the overall fitness of the protein. We study
      the statistical structure of such landscapes and apply our theory to the
      evolution by somatic hypermutation of antibody molecules composed of framework
      and complementarity-determining regions. We predict the expected number of
      replacement mutations in each region.

PMID- 7568194
TI  - Genetic heterogeneity in cystinuria: the SLC3A1 gene is linked to type I but not
      to type III cystinuria.
AB  - Cystinuria is an autosomal recessive amino-aciduria where three urinary
      phenotypes have been described (I, II, and III). An amino acid transporter gene,
      SLC3A1 (formerly rBAT), was found to be responsible for this disorder. To assess
      whether mutations in SLC3A1 are involved in different cystinuria phenotypes,
      linkage with this gene and its nearest marker (D2S119) was analyzed in 22
      families with type I and/or type III cystinuria. Linkage with heterogeneity was
      proved (alpha = 0.45; P < 0.008). Type I/I families showed homogeneous linkage to
      SLC3A1 (Zmax > 3.0 at theta = 0.00; alpha = 1), whereas types I/III and III/III
      were not linked. Our data suggest that type I cystinuria is due to mutations in
      the SLC3A1 gene, whereas another locus is responsible for type III. This result
      establishes genetic heterogeneity for cystinuria, classically considered as a
      multiallelic monogenic disease.

PMID- 7568196
TI  - Molecular cloning and characterization of a calmodulin-dependent
      phosphodiesterase enriched in olfactory sensory neurons.
AB  - The sensing of an odorant by an animal must be a rapid but transient process,
      requiring an instant response and also a speedy termination of the signal.
      Previous biochemical and electrophysiological studies suggest that one or more
      phosphodiesterases (PDEs) may play an essential role in the rapid termination of
      the odorant-induced cAMP signal. Here we report the molecular cloning,
      expression, and characterization of a cDNA from rat olfactory epithelium that
      encodes a member of the calmodulin-dependent PDE family designated as PDE1C. This
      enzyme shows high affinity for cAMP and cGMP, having a Km for cAMP much lower
      than that of any other neuronal Ca2+/calmodulin-dependent PDE. The mRNA encoding
      this enzyme is highly enriched in olfactory epithelium and is not detected in six
      other tissues tested. However, RNase protection analyses indicate that other
      alternative splice variants related to this enzyme are expressed in several other
      tissues. Within the olfactory epithelium, this enzyme appears to be expressed
      exclusively in the sensory neurons. The high affinity for cAMP of this
      Ca2+/calmodulin-dependent PDE and the fact that its mRNA is highly concentrated
      in olfactory sensory neurons suggest an important role for it in a Ca(2+)
      regulated olfactory signal termination.

PMID- 7568193
TI  - Calculating the probability of multitaxon evolutionary trees: bootstrappers
      Gambit.
AB  - The reconstruction of multitaxon trees from molecular sequences is confounded by
      the variety of algorithms and criteria used to evaluate trees, making it
      difficult to compare the results of different analyses. A global method of
      multitaxon phylogenetic reconstruction described here, Bootstrappers Gambit, can
      be used with any four-taxon algorithm, including distance, maximum likelihood,
      and parsimony methods. It incorporates a Bayesian-Jeffreys'-bootstrap analysis to
      provide a uniform probability-based criterion for comparing the results from
      diverse algorithms. To examine the usefulness of the method, the origin of the
      eukaryotes has been investigated by the analysis of ribosomal small subunit RNA
      sequences. Three common algorithms (paralinear distances, Jukes-Cantor distances,
      and Kimura distances) support the eocyte topology, whereas one (maximum
      parsimony) supports the archaebacterial topology, suggesting that the eocyte
      prokaryotes are the closest prokaryotic relatives of the eukaryotes.

PMID- 7568195
TI  - A mutant p53 antagonizes the deregulated c-myc-mediated enhancement of apoptosis
      and decrease in leukemogenicity.
AB  - Myeloid leukemic M1 cells that do not express p53 and transfected M1 clones that
      constitutively express the [Val135]p53 mutant or deregulated c-myc or
      coexpressing both genes grew autonomously in culture with a similar growth rate
      and cloning efficiency. Expression of deregulated c-myc in M1 leukemic cells
      enhanced susceptibility to induction of apoptotic cell death and resulted in a
      reduced leukemogenicity when injected into isologous mice. Expression of the
      [Val135]p53 mutant did not change cell susceptibility to induction of apoptosis
      or leukemogenicity, but expression of this mutant p53 suppressed the effects of
      deregulated c-myc on these properties. The results indicate that the [Val135]p53
      mutant can show a gain of function for susceptibility to apoptosis and
      leukemogenicity in leukemic cells with deregulated c-myc and, thus, enhance tumor
      development.

PMID- 7568197
TI  - Receptive field structure in the visual cortex: does selective stimulation induce
      plasticity?
AB  - Sensory areas of adult cerebral cortex can reorganize in response to long-term
      alterations in patterns of afferent signals. This long-term plasticity is thought
      to play a crucial role in recovery from injury and in some forms of learning.
      However, the degree to which sensory representations in primary cortical areas
      depend on short-term (i.e., minute to minute) stimulus variations remains
      unclear. A traditional view is that each neuron in the mature cortex has a fixed
      receptive field structure. An alternative view, with fundamentally different
      implications for understanding cortical function, is that each cell's receptive
      field is highly malleable, changing according to the recent history of the
      sensory environment. Consistent with the latter view, it has been reported that
      selective stimulation of regions surrounding the receptive field induces a
      dramatic short-term increase in receptive field size for neurons in the visual
      cortex [Pettet, M. W. & Gilbert, C. D. (1992) Proc. Natl. Acad. Sci. USA 89, 8366
      8370]. In contrast, we report here that there is no change in either the size or
      the internal structure of the receptive field following several minutes of
      surround stimulation. However, for some cells, overall responsiveness increases.
      These results suggest that dynamic alterations of receptive field structure do
      not underlie short-term plasticity in the mature primary visual cortex. However,
      some degree of short-term adaptability could be mediated by changes in
      responsiveness.

PMID- 7568201
TI  - Protein crosslinking studies suggest that Rhizobium meliloti C4-dicarboxylic acid
      transport protein D, a sigma 54-dependent transcriptional activator, interacts
      with sigma 54 and the beta subunit of RNA polymerase.
AB  - Rhizobium meliloti C4-dicarboxylic acid transport protein D (DCTD) activates
      transcription by a form of RNA polymerase holoenzyme that has sigma 54 as its
      sigma factor (referred to as E sigma 54). DCTD catalyzes the ATP-dependent
      isomerization of closed complexes between E sigma 54 and the dctA promoter to
      transcriptionally productive open complexes. Transcriptional activation probably
      involves specific protein-protein interactions between DCTD and E sigma 54.
      Interactions between sigma 54-dependent activators and E sigma 54 are transient,
      and there has been no report of a biochemical assay for contact between E sigma
      54 and any activator to date. Heterobifunctional crosslinking reagents were used
      to examine protein-protein interactions between the various subunits of E sigma
      54 and DCTD. DCTD was crosslinked to Salmonella typhimurium sigma 54 with the
      crosslinking reagents succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate
      and N-hydroxysulfosuccinimidyl-4-azidobenzoate. Cys-307 of sigma 54 was
      identified by site-directed mutagenesis as the residue that was crosslinked to
      DCTD. DCTD was also crosslinked to the beta subunit of Escherichia coli core RNA
      polymerase with succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, but
      not with N-hydroxysulfosuccinimidyl-4-azidobenzoate. These data suggest that
      interactions of DCTD with sigma 54 and the beta subunit may be important for
      transcriptional activation and offer evidence for interactions between a sigma 54
      dependent activator and sigma 54, as well as the beta subunit of RNA polymerase.

PMID- 7568200
TI  - Spatial learning with a minislab in the dorsal hippocampus.
AB  - We have determined the volume and location of hippocampal tissue required for
      normal acquisition of a spatial memory task. Ibotenic acid was used to make
      bilateral symmetric lesions of 20-100% of hippocampal volume. Even a small
      transverse block (minislab) of the hippocampus (down to 26% of the total) could
      support spatial learning in a water maze, provided it was at the septal (dorsal)
      pole of the hippocampus. Lesions of the septal pole, leaving 60% of the
      hippocampi intact, caused a learning deficit, although normal
      electrophysiological responses, synaptic plasticity, and preserved
      acetylcholinesterase staining argue for adequate function of the remaining
      tissue. Thus, with an otherwise normal brain, hippocampal-dependent spatial
      learning only requires a minislab of dorsal hippocampal tissue.

PMID- 7568199
TI  - Glutamate as a hippocampal neuron survival factor: an inherited defect in the
      trisomy 16 mouse.
AB  - The survival of cultured mouse hippocampal neurons was found to be greatly
      enhanced by micromolar concentrations of the excitatory neurotransmitter
      glutamate. Blockade of kainate/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid) glutamate receptors increased the rate of neuron death,
      suggesting that endogenous glutamate in the cultures promotes survival. Addition
      of glutamate (0.5-1 microM) further increased neuron survival, whereas glutamate
      in excess of 20 microM resulted in increased death. Thus, the survival vs.
      glutamate dose-response relation is bell-shaped with an optimal glutamate
      concentration near 1 microM. We found that hippocampal neurons from mice with the
      genetic defect trisomy 16 (Ts16) died 2-3 times faster than normal (euploid)
      neurons. Moreover, glutamate, at all concentrations tested, failed to increase
      survival of Ts16 neurons. In contrast, the neurotrophic polypeptide basic
      fibroblast growth factor did increase the survival of Ts16 and euploid neurons.
      Ts16 is a naturally occurring mouse genetic abnormality, the human analog of
      which (Down syndrome) leads to altered brain development and Alzheimer disease.
      These results demonstrate that the Ts16 genotype confers a defect in the
      glutamate-mediated survival response of hippocampal neurons and that this defect
      can contribute to their accelerated death.

PMID- 7568198
TI  - Characterization and functional ordering of Slu7p and Prp17p during the second
      step of pre-mRNA splicing in yeast.
AB  - Temperature-sensitive alleles in four genes (slu7-1, prp16-2, prp17-1, and prp18
      1) are known to confer a specific block to the second chemical step of pre-mRNA
      splicing in vivo in the yeast Saccharomyces cerevisiae. Previous studies showed
      that Prp16p and Prp18p are required solely for the second step in vitro. The RNA
      dependent ATPase, Prp16p, functions at a stage in splicing when ATP is required,
      whereas Prp18p functions at an ATP-independent stage. Here we use immunodepletion
      to show that the roles of Slu7p and Prp17p are also confined to the second step
      of splicing. We find that extracts depleted of Prp17p require both Prp17p and ATP
      for slicing complementation, whereas extracts depleted of Slu7p require only the
      addition of Slu7p. These different ATP requirements suggest that Prp16p and
      Prp17p function before Prp18p and Slu7p. Although SLU7 encodes an essential gene
      product, we find that a null allele of prp17 is temperature-sensitive for growth
      and has a partial splicing defect in vitro. Finally, high-copy suppression
      experiments indicate functional interactions between PRP16 and PRP17, PRP16 and
      SLU7, and SLU7 and PRP18. Taken together, the results suggest that these four
      factors may function within a multi-component complex that has both an ATP
      dependent and an ATP-independent role in the second step of pre-mRNA splicing.

PMID- 7568202
TI  - Kinetics of spindle pole body separation in budding yeast.
AB  - In the budding yeast Saccharomyces cerevisiae, the spindle pole body (SPB) serves
      as the microtubule-organizing center and is the functional analog of the
      centrosome of higher organisms. By expressing a fusion of a yeast SPB-associated
      protein to the Aequorea victoria green fluorescent protein, the movement of the
      SPBs in living yeast cells undergoing mitosis was observed by fluorescence
      microscopy. The ability to visualize SPBs in vivo has revealed previously
      unidentified mitotic events. During anaphase, the mitotic spindle has four
      sequential activities: alignment at the mother-daughter junction, fast
      elongation, translocation into the bud, and slow elongation. These results
      indicate that distinct forces act upon the spindle at different times during
      anaphase.

PMID- 7568204
TI  - Neighboring base composition and transversion/transition bias in a comparison of
      rice and maize chloroplast noncoding regions.
AB  - The correspondence between the transversion/transition ratio and the neighboring
      base composition in chloroplast DNA is examined. For 18 noncoding regions of the
      chloroplast genome, alignments between rice (Oryza sativa) and maize (Zea mays)
      were generated by two different methods. Difficulties of aligning noncoding DNA
      are discussed, and the alignments are analyzed in a manner that reduces alignment
      artifacts. Sequence divergence is < 10%, so multiple substitutions at a site are
      assumed to be rare. Observed substitutions were analyzed with respect to the A+T
      content of the two immediately flanking bases. It is shown that as this content
      increases, the proportion of transversions also increases. When both the 5'- and
      3'-flanking nucleotides are G or C (A+T content of 0), only 25% of the observed
      substitutions are transversions. However, when both the 5'- and 3'-flanking
      nucleotides are A or T (A+T content of 2), 57% of the observed substitutions are
      transversions. Therefore, the influence of flanking base composition on
      substitutions, previously reported for a single noncoding region, is a general
      feature of the chloroplast genome.

PMID- 7568203
TI  - Dissociation between changes in cytoplasmic free Ca2+ concentration and insulin
      secretion as evidenced from measurements in mouse single pancreatic islets.
AB  - Simultaneous measurements of cytosolic free Ca2+ concentration and insulin
      release, in mouse single pancreatic islets, revealed a direct correlation only
      initially after stimulation with glucose or K+. Later, there is an apparent
      dissociation between these two parameters, with translocation of alpha and
      epsilon isoenzymes of protein kinase C to membranes and simultaneous
      desensitization of insulin release in response to glucose. Recovery of insulin
      release, without any concomitant changes in cytosolic free Ca2+ concentration,
      after addition of phorbol 12-myristate 13-acetate, okadaic acid, and forskolin
      supports the notion that the desensitization process is accounted for by
      dephosphorylation of key regulatory sites of the insulin exocytotic machinery.

PMID- 7568205
TI  - Regulation of yeast phospholipid biosynthetic gene expression in response to
      inositol involves two superimposed mechanisms.
AB  - Transcription of phospholipid biosynthetic genes in the yeast Saccharomyces
      cerevisiae is maximally derepressed when cells are grown in the absence of
      inositol and repressed when the cells are grown in its presence. We have
      previously suggested that this response to inositol may be dictated by regulating
      transcription of the cognate activator gene, INO2. However, it was also known
      that cells which harbor a mutant opi1 allele express constitutively derepressed
      levels of target genes (INO1 and CHO1), implicating the OPI1 negative regulatory
      gene in the response to inositol. These observations suggested that the response
      to inositol may involve both regulation of INO2 transcription as well as OPI1
      mediated repression. We investigated these possibilities by examining the effect
      of inositol on target gene expression in a strain containing the INO2 gene under
      control of the GAL1 promoter. In this strain, transcription of the INO2 gene was
      regulated in response to galactose but was insensitive to inositol. The
      expression of the INO1 and CHO1 target genes was still responsive to inositol
      even though expression of the INO2 gene was unresponsive. However, the level of
      expression of the INO1 and CHO1 target genes correlated with the level of INO2
      transcription. Furthermore, the effect of inositol on target gene expression was
      eliminated by deleting the OPI1 gene in the GAL1-INO2-containing strain. These
      data suggest that the OPI1 gene product is the primary target (sensor) of the
      inositol response and that derepression of INO2 transcription determines the
      degree of expression of the target genes.

PMID- 7568206
TI  - DNA loops induced by cooperative binding of transcriptional activator proteins
      and preinitiation complexes.
AB  - DNA conformational changes are essential for the assembly of multiprotein
      complexes that contact several DNA sequence elements. An approach based on atomic
      force microscopy was chosen to visualize specific protein-DNA interactions
      occurring on eukaryotic class II nuclear gene promoters. Here we report that
      binding of the transcription regulatory protein Jun to linearized plasmid DNA
      containing the consensus AP-1 binding site upstream of a class II gene promoter
      leads to bending of the DNA template. This binding of Jun was found to be
      essential for the formation of preinitiation complexes (PICs). The cooperative
      binding of Jun and PIC led to looping of DNA at the protein binding sites. These
      loops were not seen in the absence of either PICs, Jun, or the AP-1 binding site,
      suggesting a direct interaction between DNA-bound Jun homodimers and proteins
      bound to the core promoter. This direct visualization of functional
      transcriptional complexes confirms the theoretical predictions for the mode of
      gene regulation by trans-activating proteins.

PMID- 7568207
TI  - Human white blood cells contain cyclobutyl pyrimidine dimer photolyase.
AB  - Although enzymatic photoreactivation of cyclobutyl pyrimidine dimers in DNA is
      present in almost all organisms, its presence in placental mammals is
      controversial. We tested human white blood cells for photolyase by using three
      defined DNAs (supercoiled pET-2, nonsupercoiled bacteriophage lambda, and a
      defined-sequence 287-bp oligonucleotide), two dimer-specific endonucleases (T4
      endonuclease V and UV endonuclease from Micrococcus luteus), and three assay
      methods. We show that human white blood cells contain photolyase that can
      photorepair pyrimidine dimers in defined supercoiled and linear DNAs and in a 287
      bp oligonucleotide and that human photolyase is active on genomic DNA in intact
      human cells.

PMID- 7568209
TI  - Systemic gene therapy: biodistribution and long-term expression of a transgene in
      mice.
AB  - We have investigated the in vivo efficacy of a systemic gene transfer method,
      which combines a liposomal delivery system (DLS liposomes) with episomally
      replicative DNA plasmids to effect long-term expression of a transgene in cells.
      A single i.v. injection of a plasmid DNA vector containing the luciferase gene as
      a marker was administered with the DLS liposomes in BALB/c mice. The luciferase
      gene and its product were found in all mouse tissues tested as determined by PCR
      analysis and immunohistochemistry. Luciferase activity was also detected in all
      tissues tested and was present in lung, liver, spleen, and heart up to 3 months
      postinjection. In contrast to the nonepisomal vectors tested (pRSV-luc and
      pCMVintlux), human papovavirus (BKV)-derived episomal vectors showed long-term
      transgene expression. We found that these episomal vectors replicated
      extrachromosomally in lung 2 weeks postinjection. Results indicated that
      transgene expression in specific tissues depended on the promoter element used,
      DNA/liposome formulation, dose of DNA per injection, and route of administration.

PMID- 7568208
TI  - The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present
      in a wide range of proteins, including MLL, AF10, and MLLT6 proteins.
AB  - We have identified and further characterized a Caenorhabditis elegans gene, CEZF,
      that encodes a protein with substantial homology to the zinc finger and leucine
      zipper motifs of the human gene products AF10, MLLT6, and BR140. The first part
      of the zinc finger region of CEZF has strong similarity to the corresponding
      regions of AF10 (66%) and MLLT6 (64%) at the cDNA level. As this region is
      structurally different from previously described zinc finger motifs, sequence
      homology searches were done. Twenty-five other proteins with a similar motif were
      identified. Because the functional domain of this motif is potentially disrupted
      in leukemia-associated chromosomal translocations, we propose the name of
      leukemia-associated protein (LAP) finger. On the basis of these comparisons, the
      LAP domain consensus sequence is Cys1-Xaa1-2-Cys2-Xaa9-21-Cys3-Xaa2-4 -Cys4-Xaa4
      5-His5-Xaa2-Cys6-Xaa12-46 - Cys7-Xaa2-Cys8, where subscripted numbers represent
      the number of amino acid residues. We review the evidence that this motif binds
      zinc, is the important DNA-binding domain in this group of regulatory proteins,
      and may be involved in leukemogenesis.

PMID- 7568212
TI  - Chemotactic signal integration in bacteria.
AB  - Chemotactic signaling in Escherichia coli involves transmission of both negative
      and positive signals. In order to examine mechanisms of signal processing,
      behavioral responses to dual inputs have been measured by using photoactivable
      "caged" compounds, computer video analysis, and chemoreceptor deletion mutants.
      Signaling from Tar and Tsr, two receptors that sense amino acids and pH, was
      studied. In a Tar deletion mutant the photoactivated release of protons, a Tsr
      repellent, and of serine, a Tsr attractant, in separate experiments at pH 7.0
      resulted in tumbling (negative) or smooth-swimming (positive) responses in ca. 50
      and 140 ms, respectively. Simultaneous photorelease of protons and serine
      resulted in a single tumbling or smooth-swimming response, depending on the
      relative amounts of the two effectors. In contrast, in wild-type E. coli, proton
      release at pH 7.0 resulted in a biphasic response that was attributed to Tsr
      mediated tumbling followed by Tar-mediated smooth-swimming. In wild-type E. coli
      at more alkaline pH values the Tar-mediated signal was stronger than the Tsr
      signal, resulting in a strong smooth-swimming response preceded by a diminished
      tumbling response. These observations imply that (i) a single receptor time
      averages the binding of different chemotactic ligands generating a single
      response; (ii) ligand binding to different receptors can result in a
      nonintegrated response with the tumbling response preceding the smooth-swimming
      response; (iii) however, chemotactic signals of different intensities derived
      from different receptors can also result in an apparently integrated response;
      and (iv) the different chemotactic responses to protons at neutral and alkaline
      pH may contribute to E. coli migration toward neutrality.

PMID- 7568210
TI  - Ligand-directed retroviral targeting of human breast cancer cells.
AB  - We explored the feasibility of designing retroviral vectors that can target human
      breast cancer cells with characteristic receptors via ligand-receptor
      interaction. The ecotropic Moloney murine leukemia virus envelope was modified by
      insertion of sequences encoding human heregulin. Ecotropic virus, which normally
      does not infect human cells, when pseudotyped with the modified envelope protein
      now crosses species to infect human breast cancer cell lines that overexpress HER
      2 (human epidermal growth factor receptor; also called ERBB2) and HER-4 (also
      called ERBB4), while human breast cancer cell lines expressing low levels of
      these receptors remain resistant to infection. Since about 20% of human breast
      cancers overexpress HER-2 and some of breast cancer cell lines overexpress both
      HER-2 and HER-4, cell-specific targeting of retroviral vectors may provide a
      different approach for in vivo gene therapy of this type of breast cancer.

PMID- 7568211
TI  - Analysis of homeodomain function by structure-based design of a transcription
      factor.
AB  - The homeodomain is a 60-amino acid module which mediates critical protein-DNA and
      protein-protein interactions for a large family of regulatory proteins. We have
      used structure-based design to analyze the ability of the Oct-1 homeodomain to
      nucleate an enhancer complex. The Oct-1 protein regulates herpes simplex virus
      (HSV) gene expression by participating in the formation of a multiprotein complex
      (C1 complex) which regulates alpha (immediate early) genes. We recently described
      the design of ZFHD1, a chimeric transcription factor containing zinc fingers 1
      and 2 of Zif268, a four-residue linker, and the Oct-1 homeodomain. In the
      presence of alpha-transinduction factor and C1 factor, ZFHD1 efficiently
      nucleates formation of the C1 complex in vitro and specifically activates gene
      expression in vivo. The sequence specificity of ZFHD1 recruits C1 complex
      formation to an enhancer element which is not efficiently recognized by Oct-1.
      ZFHD1 function depends on the recognition of the Oct-1 homeodomain surface. These
      results prove that the Oct-1 homeodomain mediates all the protein-protein
      interactions that are required to efficiently recruit alpha-transinduction factor
      and C1 factor into a C1 complex. The structure-based design of transcription
      factors should provide valuable tools for dissecting the interactions of DNA
      bound domains in other regulatory circuits.

PMID- 7568213
TI  - Cloning and expression of the cDNA of chicken cation-independent mannose-6
      phosphate receptor.
AB  - We cloned and sequenced the 8767-bp full-length cDNA for the chicken cation
      independent mannose-6-phosphate receptor (CI-MPR), of interest because, unlike
      its mammalian homologs, it does not bind insulin-like growth factor II (IGF-II).
      The cDNA encodes a protein of 2470 aa that includes a putative signal sequence,
      an extracytoplasmic domain consisting of 15 homologous repeat sequences, a 23
      residue transmembrane sequence, and a 161-residue cytoplasmic sequence. Overall,
      it shows 60% sequence identity with human and bovine CI-MPR homologs, and all but
      two of 122 cysteine residues are conserved. However, it shows much less homology
      in the N-terminal signal sequence, in repeat 11, which is proposed to contain the
      IGF-II-binding site in mammalian CI-MPR homologs, and in the 14-aa residue
      segment in the cytoplasmic sequence that has been proposed to mediate G-protein
      coupled signal transduction in response to IGF-II binding by the human CI-MPR.
      Transient expression in COS-7 cells produced a functional CI-MPR which exhibited
      mannose-6-phosphate-inhibitable binding and mediated endocytosis of recombinant
      human beta-glucuronidase. Expression of the functional chicken CI-MPR in mice
      lacking the mammalian CI-MPR should clarify the controversy over the
      physiological role of the IGF-II-binding site in mammalian CI-MPR homologs.

PMID- 7568214
TI  - Role of phospholipids containing docosahexaenoyl chains in modulating the
      activity of protein kinase C.
AB  - It is known that the phospholipids of the brain cells of fish are altered during
      cold adaptation. In particular, the 1-monounsaturated 2-polyunsaturated
      phosphatidylethanolamines (PEs) increase 2- to 3-fold upon adaptation to cold.
      One of the most striking changes is in the 18:1/22:6 species of PE. We determined
      how this lipid affected the bilayer-to-hexagonal-phase transition temperature of
      16:1/16:1 PE. We found that it was more effective in lowering this transition
      temperature than were other, less unsaturated, PE species. In addition, it was
      not simply the presence of the 18:1/22:6 acyl chains which caused this effect,
      since the 18:1/22:6 species of phosphatidylcholine had the opposite effect on
      this transition temperature. Zwitterionic substances that lower the bilayer-to
      hexagonal-phase transition temperature often cause an increase in the activity of
      protein kinase C (PKC). Indeed, the 18:1/22:6 PE caused an increase in the rate
      of histone phosphorylation by PKC which was greater than that caused by other,
      less unsaturated, PEs. The 18:1/22:6 phosphatidylcholine had no effect on this
      enzyme. The stimulation of the activity of PKC by the 18:1/22:6 PE is a
      consequence of this lipid's increasing the partitioning of PKC to the membrane.

PMID- 7568215
TI  - Rescue of adult mouse motoneurons from injury-induced cell death by glial cell
      line-derived neurotrophic factor.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been shown to rescue
      developing motoneurons in vivo and in vitro from both naturally occurring and
      axotomy-induced cell death. To test whether GDNF has trophic effects on adult
      motoneurons, we used a mouse model of injury-induced adult motoneuron
      degeneration. Injuring adult motoneuron axons at the exit point of the nerve from
      the spinal cord (avulsion) resulted in a 70% loss of motoneurons by 3 weeks
      following surgery and a complete loss by 6 weeks. Half of the loss was prevented
      by GDNF treatment. GDNF also induced an increase (hypertrophy) in the size of
      surviving motoneurons. These data provide strong evidence that the survival of
      injured adult mammalian motoneurons can be promoted by a known neurotrophic
      factor, suggesting the potential use of GDNF in therapeutic approaches to adult
      onset motoneuron diseases such as amyotrophic lateral sclerosis.

PMID- 7568217
TI  - Transcription termination of RNA polymerase I due to a T-rich element interacting
      with Reb1p.
AB  - All transcription terminators for RNA polymerase I (pol I) that have been studied
      so far, ranging from yeast to humans, require a specific DNA binding protein to
      cause termination. In yeast, this terminator protein has been identified as
      Reb1p. We now show that, in addition to the binding site for Reb1p, the yeast pol
      I terminator also requires the presence of a T-rich region coding for the last 12
      nucleotides of the transcript. Reb1p cooperates with this T-rich element, both to
      pause the polymerase and to effect release of the transcript. These findings have
      implications for the termination mechanism used by all three nuclear RNA
      polymerases, since all three are known to pause at this terminator.

PMID- 7568216
TI  - Specificity of dimer formation in tropomyosins: influence of alternatively
      spliced exons on homodimer and heterodimer assembly.
AB  - Tropomyosins consist of nearly 100% alpha-helix and assemble into parallel and in
      register coiled-coil dimers. In vitro it has been established that nonmuscle as
      well as native muscle tropomyosins can form homodimers. However, a mixture of
      muscle alpha and beta tropomyosin subunits results in the formation of the
      thermodynamically more stable alpha/beta heterodimer. Although the assembly
      preference of the muscle tropomyosin heterodimer can be understood
      thermodynamically, the presence of multiple tropomyosin isoforms expressed in
      nonmuscle cells points toward a more complex principle for determining dimer
      formation. We have investigated the dimerization of rat tropomyosins in living
      cells by the use of epitope tagging with a 16-aa sequence of the influenza
      hemagglutinin. Employing transfection and immunoprecipitation techniques, we have
      analyzed the dimers formed by muscle and nonmuscle tropomyosins in rat
      fibroblasts. We demonstrate that the information for homo- versus
      heterodimerization is contained within the tropomyosin molecule itself and that
      the information for the selectivity is conferred by the alternatively spliced
      exons. These results have important implications for models of the regulation of
      cytoskeletal dynamics.

PMID- 7568218
TI  - Cloning, expression, and function of TFC5, the gene encoding the B" component of
      the Saccharomyces cerevisiae RNA polymerase III transcription factor TFIIIB.
AB  - TFC5, the unique and essential gene encoding the B" component of the
      Saccharomyces cerevisiae RNA polymerase III transcription factor (TF)IIIB has
      been cloned. It encodes a 594-amino acid protein (67,688 Da). Escherichia coli
      produced B" has been used to reconstitute entirely recombinant TFIIIB that is
      fully functional for TFIIIC-directed, as well as TATA box-dependent, DNA binding
      and transcription. The DNase I footprints of entirely recombinant TFIIIB,
      composed of B", the 67-kDa Brf, and TATA box-binding protein, and TFIIIB
      reconstituted with natural B" are indistinguishable. A truncated form of B"
      lacking 39 N-terminal and 107 C-terminal amino acids is also functional for
      transcription.

PMID- 7568221
TI  - Simple model of protein folding kinetics.
AB  - A simple model of the kinetics of protein folding is presented. The reaction
      coordinate is the "correctness" of a configuration compared with the native
      state. The model has a gap in the energy spectrum, a large configurational
      entropy, a free energy barrier between folded and partially folded states, and a
      good thermodynamic folding transition. Folding kinetics is described by a master
      equation. The folding time is estimated by means of a local thermodynamic
      equilibrium assumption and then is calculated both numerically and analytically
      by solving the master equation. The folding time has a maximum near the folding
      transition temperature and can have a minimum at a lower temperature.

PMID- 7568219
TI  - Antibody-targeted superantigens are potent inducers of tumor-infiltrating T
      lymphocytes in vivo.
AB  - Recruitment of antigen-specific tumor-infiltrating lymphocytes (TILs) is a major
      goal for immunotherapy of malignant tumours. We now describe that T-cell
      activating superantigens targeted to a tumor by monoclonal antibodies induced
      large numbers of pseudospecific TILs and eradication of micrometastases. As a
      model for tumor micrometastases, syngeneic B16 melanoma cells transfected with
      the human colon carcinoma antigen C215 were injected intravenously into C57BL/6
      mice and therapy with an anti-C215 Fab fragment-staphylococcal enterotoxin A
      (C215Fab-SEA) fusion protein reacting with the C215 antigen was initiated when
      visible lung metastases were established. More than 90% reduction of the number
      of lung metastases was observed when mice carrying 5-day-old established lung
      metastases were treated with C215Fab-SEA. The antitumor effect of C215Fab-SEA was
      shown to be T-cell-dependent since no therapeutic effect was seen in T-cell
      deficient nude mice. Depletion of T-cell subsets by injection of monoclonal
      antibody demonstrated that CD8+ cells were the most prominent effector cells
      although some contribution from CD4+ cells was also noted. C215Fab-SEA treatment
      induced massive tumor infiltration of CD4+ and CD8+ T cells, while only scattered
      T cells were observed in untreated tumors. SEA treatment alone induced a slight
      general inflammatory response in the lung parenchyme, but no specific
      accumulation of T cells was seen in the tumor. TILs induced by C215Fab-SEA were
      mainly CD8+ but a substantial number of CD4+ cells were also present.
      Immunohistochemical analysis showed strong production of the tumoricidal
      cytokines tumor necrosis factor alpha and interferon gamma in the tumor. Thus,
      the C215Fab-SEA fusion protein targets effector T lymphocytes to established
      tumors in vivo and provokes a strong local antitumor immune response.

PMID- 7568220
TI  - X-ray structure of clotting factor IXa: active site and module structure related
      to Xase activity and hemophilia B.
AB  - Hereditary deficiency of factor IXa (fIXa), a key enzyme in blood coagulation,
      causes hemophilia B, a severe X chromosome-linked bleeding disorder afflicting 1
      in 30,000 males; clinical studies have identified nearly 500 deleterious
      variants. The x-ray structure of porcine fIXa described here shows the atomic
      origins of the disease, while the spatial distribution of mutation sites suggests
      a structural model for factor X activation by phospholipid-bound fIXa and
      cofactor VIIIa. The 3.0-A-resolution diffraction data clearly show the structures
      of the serine proteinase module and the two preceding epidermal growth factor
      (EGF)-like modules; the N-terminal Gla module is partially disordered. The
      catalytic module, with covalent inhibitor D-Phe-1I-Pro-2I-Arg-3I chloromethyl
      ketone, most closely resembles fXa but differs significantly at several
      positions. Particularly noteworthy is the strained conformation of Glu-388, a
      residue strictly conserved in known fIXa sequences but conserved as Gly among
      other trypsin-like serine proteinases. Flexibility apparent in electron density
      together with modeling studies suggests that this may cause incomplete active
      site formation, even after zymogen, and hence the low catalytic activity of fIXa.
      The principal axes of the oblong EGF-like domains define an angle of 110 degrees,
      stabilized by a strictly conserved and fIX-specific interdomain salt bridge. The
      disorder of the Gla module, whose hydrophobic helix is apparent in electron
      density, can be attributed to the absence of calcium in the crystals; we have
      modeled the Gla module in its calcium form by using prothrombin fragment 1. The
      arched module arrangement agrees with fluorescence energy transfer experiments.
      Most hemophilic mutation sites of surface fIX residues occur on the concave
      surface of the bent molecule and suggest a plausible model for the membrane-bound
      ternary fIXa-FVIIIa-fX complex structure: fIXa and an equivalently arranged fX
      arch across an underlying fVIIIa subdomain from opposite sides; the stabilizing
      fVIIIa interactions force the catalytic modules together, completing fIXa active
      site formation and catalytic enhancement.

PMID- 7568222
TI  - A general strategy for producing conditional alleles of Src-like tyrosine
      kinases.
AB  - The Src-like tyrosine kinases require membrane localization for transformation
      and probably for their normal role in signal transduction. We utilized this
      characteristic to prepare Src-like tyrosine kinases that can be readily activated
      with the rationally designed chemical inducer of dimerization FK1012.
      Dimerization of cytoplasmic Src-like tyrosine kinases was not sufficient for
      signaling, but their recruitment to the plasma membrane led to the rapid
      activation of transcription factors identical to those regulated by crosslinking
      the antigen receptor. Moreover, recruitment of activated Src-like kinases to the
      membrane replaced signaling by the T-lymphocyte antigen receptor complex, leading
      to the activation of both the Ras/protein kinase C and Ca2+/calcineurin pathways
      normally activated by antigen receptor signaling. Since these chemical inducers
      of dimerization are cell permeable, this approach permits the production of
      conditional alleles of any of the Src-like tyrosine kinases, thereby allowing a
      delineation of their developmental roles.

PMID- 7568224
TI  - Expression in cochlea and retina of myosin VIIa, the gene product defective in
      Usher syndrome type 1B.
AB  - Myosin VIIa is a newly identified member of the myosin superfamily of actin-based
      motors. Recently, the myosin VIIa gene was identified as the gene defective in
      shaker-1, a recessive deafness in mice [Gibson, F., Walsh, J., Mburu, P., Varela,
      A., Brown, K.A., Antonio, M., Beisel, K.W., Steel, K.P. & Brown, S.D.M. (1995)
      Nature (London) 374, 62-64], and in human Usher syndrome type 1B, an inherited
      disease characterized by congenital deafness, vestibular dysfunction, and
      retinitis pigmentosa [Weil, D., Blanchard, S., Kaplan, J., Guilford, P., Gibson,
      F., Walsh, J., Mburu, P., Varela, A., Levilliers, J., Weston, M.D., Kelley, P.M.,
      Kimberling, W.J., Wagenaar, M., Levi-Acobas, F., Larget-Piet, D., Munnich, A.,
      Steel, K.P., Brown, S.D.M. & Petit, C. (1995) Nature (London) 374, 60-61]. To
      understand the normal function of myosin VIIa and how it could cause these
      disease phenotypes when defective, we generated antibodies specific to the tail
      portion of this unconventional myosin. We found that myosin VIIa was expressed in
      cochlea, retina, testis, lung, and kidney. In cochlea, myosin VIIa expression was
      restricted to the inner and outer hair cells, where it was found in the apical
      stereocilia as well as the cytoplasm. In the eye, myosin VIIa was expressed by
      the retinal pigmented epithelial cells, where it was enriched within the apical
      actin-rich domain of this cell type. The cell-specific localization of myosin
      VIIa suggests that the blindness and deafness associated with Usher syndrome is
      due to lack of proper myosin VIIa function within the cochlear hair cells and the
      retinal pigmented epithelial cells.

PMID- 7568225
TI  - Two redundant systems maintain levels of resident proteins within the yeast
      endoplasmic reticulum.
AB  - The Saccharomyces cerevisiae gene ERD2 is responsible for the retrieval of
      lumenal resident proteins of the endoplasmic reticulum (ER) lost to the next
      secretory compartment. Previous studies have suggested that the retrieval of
      proteins by ERD2 is not essential. Here, we find that ERD2-mediated retrieval is
      not an essential process only because, on its failure, a second inducible system
      acts to maintain levels of ER proteins. The second system is controlled by the ER
      membrane-bound kinase encoded by IRE1. We conclude that IRE1 and ERD2 together
      maintain normal concentrations of resident proteins within the ER.

PMID- 7568226
TI  - A maximum likelihood algorithm for genome mapping of cytogenetic loci from
      meiotic configuration data.
AB  - Frequencies of meiotic configurations in cytogenetic stocks are dependent on
      chiasma frequencies in segments defined by centromeres, breakpoints, and
      telomeres. The expectation maximization algorithm is proposed as a general method
      to perform maximum likelihood estimations of the chiasma frequencies in the
      intervals between such locations. The estimates can be translated via mapping
      functions into genetic maps of cytogenetic landmarks. One set of observational
      data was analyzed to exemplify application of these methods, results of which
      were largely concordant with other comparable data. The method was also tested by
      Monte Carlo simulation of frequencies of meiotic configurations from a
      monotelodisomic translocation heterozygote, assuming six different sample sizes.
      The estimate averages were always close to the values given initially to the
      parameters. The maximum likelihood estimation procedures can be extended readily
      to other kinds of cytogenetic stocks and allow the pooling of diverse cytogenetic
      data to collectively estimate lengths of segments, arms, and chromosomes.

PMID- 7568223
TI  - Signal transduction in T lymphocytes using a conditional allele of Sos.
AB  - While Ras activation has been shown to play an important role in signal
      transduction by the T-lymphocyte antigen receptor, the mechanism of its
      activation in T cells is unclear. Membrane localization of the guanine nucleotide
      exchange factor Sos, but not Vav or Dbl, was sufficient for Ras-mediated
      signaling in T lymphocytes. Activation of Sos appears to involve membrane
      recruitment and not allosteric changes, because interaction of Sos with the
      linking molecule Grb-2 was not required for Ras activation. To extend this
      analysis, we constructed a modified Sos that could be localized to the membrane
      inducibly by using a rationally designed chemical inducer of dimerization,
      FK1012. The role of Grb-2 in signaling was mimicked with this technique, which
      induced the association of a modified Sos with the membrane, resulting in rapid
      activation of Ras-induced signaling. In contrast, inducible localization of Grb-2
      to the membrane did not activate signaling and suggests that the interaction of
      Grb-2 with Sos in T cells is subject to regulation. This conditional allele of
      Sos demonstrates that membrane localization of Sos is sufficient for Ras
      activation in T cells and indicates that the role of Grb-2 is to realize the
      biologic advantages of linker-mediated dimerization: enhanced specificity and
      favorable kinetics for signaling. This method of generating conditional alleles
      may also be useful in dissecting other signal transduction pathways regulated by
      protein localization or protein-protein interactions.

PMID- 7568227
TI  - Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after
      osmotic blood-brain barrier disruption.
AB  - The delivery of viral vectors to the brain for treatment of intracerebral tumors
      is most commonly accomplished by stereotaxic inoculation directly into the tumor.
      However, the small volume of distribution by inoculation may limit the efficacy
      of viral therapy of large or disseminated tumors. We have investigated mechanisms
      to increase vector delivery to intracerebral xenografts of human LX-1 small-cell
      lung carcinoma tumors in the nude rat. The distribution of Escherichia coli lacZ
      transgene expression from primary viral infection was assessed after delivery of
      recombinant virus by intratumor inoculation or intracarotid infusion with or
      without osmotic disruption of the blood-brain barrier (BBB). These studies used
      replication-compromised herpes simplex virus type 1 (HSV; vector RH105) and
      replication-defective adenovirus (AdRSVlacZ), which represent two of the most
      commonly proposed viral vectors for tumor therapy. Transvascular delivery of both
      viruses to intracerebral tumor was demonstrated when administered intraarterially
      (i.a.) after osmotic BBB disruption (n = 9 for adenovirus; n = 7 for HSV), while
      no virus infection was apparent after i.a. administration without BBB
      modification (n = 8 for adenovirus; n = 4 for HSV). The thymidine kinase-negative
      HSV vector infected clumps of tumor cells as a result of its ability to replicate
      selectively in dividing cells. Osmotic BBB disruption in combination with i.a.
      administration of viral vectors may offer a method of global delivery to treat
      disseminated brain tumors.

PMID- 7568229
TI  - APX-1 can substitute for its homolog LAG-2 to direct cell interactions throughout
      Caenorhabditis elegans development.
AB  - The homologous LAG-2 and APX-1 membrane proteins are putative signaling ligands
      in the GLP-1/LIN-12 signal-transduction pathway in Caenorhabditis elegans.
      Normally, LAG-2 and APX-1 mediate distinct cell interactions. Here, we
      demonstrate that APX-1, which normally interacts with GLP-1 in the early embryo,
      can substitute for LAG-2 throughout development. When expressed under control of
      the lag-2 promoter, an apx-1 cDNA can completely rescue a lag-2 null mutant. To
      substitute for LAG-2, APX-1 must be able to interact with both GLP-1 and LIN-12
      receptors and to mediate a variety of cell interactions during development.
      Therefore, APX-1 and LAG-2 are essentially equivalent in their ability to
      influence receptor activity. On the basis of this result, we suggest that the
      existence of multiple-signaling ligands in the LIN-12/GLP-1 signal transduction
      pathway does not reflect the evolution of functionally distinct proteins but
      rather the imposition of distinct controls of gene expression upon functionally
      similar proteins. Finally, we propose that the specification of distinct cell
      fates by the LIN-12/GLP-1 signal-transduction pathway relies on activities
      functioning downstream of the ligand and receptor, rather than on specific ligand
      receptor interactions.

PMID- 7568228
TI  - Autocrine/paracrine role of insulin-related growth factors in neurogenesis: local
      expression and effects on cell proliferation and differentiation in retina.
AB  - Early neurogenesis progresses by an initial massive proliferation of
      neuroepithelial cells followed by a sequential differentiation of the various
      mature neural cell types. The regulation of these processes by growth factors is
      poorly understood. We intend to understand, in a well-defined biological system,
      the embryonic chicken retina, the role of the insulin-related growth factors in
      neurogenesis. We demonstrate the local presence of signaling elements together
      with a biological response to the factors. Neuroretina at days 6-8 of embryonic
      development (E6-E8) expressed proinsulin/insulin and insulin-like growth factor I
      (IGF-I) mRNAs as well as insulin receptor and IGF type I receptor mRNAs. In
      parallel with this in vivo gene expression, E5 cultured neuroretinas synthesized
      and released to the medium a metabolically radiolabeled immunoprecipitable
      insulin-related peptide. Furthermore, insulin-related immunoreactive material
      with a HPLC mobility close to that of proinsulin was found in the E6-E8 vitreous
      humor. Exogenous chicken IGF-I, human insulin, and human proinsulin added to E6
      cultured neuroretinas showed relatively close potencies stimulating
      proliferation, as determined by [methyl-3H]thymidine incorporation, with a
      plateau reached at 10(-8) M. These factors also stimulated neuronal
      differentiation, indicated by the expression of the neuron-specific antigen G4.
      Thus, insulin-related growth factors, interestingly including proinsulin, are
      present in the developing chicken retina and appear to play an
      autocrine/paracrine stimulatory role in the progression of neurogenesis.

PMID- 7568230
TI  - Structures of the apo- and the metal ion-activated forms of the diphtheria tox
      repressor from Corynebacterium diphtheriae.
AB  - The diphtheria tox repressor (DtxR) of Corynebacterium diphtheriae plays a
      critical role in the regulation of diphtheria toxin expression and the control of
      other iron-sensitive genes. The crystal structures of apo-DtxR and of the metal
      ion-activated form of the repressor have been solved and used to identify motifs
      involved in DNA and metal ion binding. Residues involved in binding of the
      activated repressor to the diphtheria tox operator, glutamine 43, arginine 47,
      and arginine 50, were located and confirmed by site-directed mutagenesis.
      Previous biochemical and genetic data can be explained in terms of these
      structures. Conformational differences between apo- and Ni-DtxR are discussed
      with regard to the mechanism of action of this repressor.

PMID- 7568231
TI  - Deletion of high-avidity T cells by thymic epithelium.
AB  - Tolerance induction by thymic epithelium induces a state of so-called "split
      tolerance," characterized in vivo by tolerance and in vitro by reactivity to a
      given thymically expressed antigen. Using a model major histocompatibility
      complex class I antigen, H-2Kb (Kb), three mechanisms of thymic epithelium
      induced tolerance were tested: induction of tolerance of tissue-specific antigens
      exclusively, selective inactivation of T helper cell-independent cytotoxic T
      lymphocytes, and deletion of high-avidity T cells. To this end, thymic anlagen
      from Kb-transgenic embryonic day 10 mouse embryos, taken before colonization by
      cells of hemopoietic origin, were grafted to nude mice. Tolerance by thymic
      epithelium was not tissue-specific, since Kb-bearing skin and spleen grafts were
      maintained indefinitely. Only strong priming in vivo could partially overcome the
      tolerant state and induce rejection of some skin grafts overexpressing transgenic
      Kb. Furthermore, the hypothesis that thymic epithelium selectively inactivates
      those T cells that reject skin grafts in a T helper-independent fashion could not
      be supported. Thus, when T-cell help was provided by a second skin graft bearing
      an additional major histocompatibility complex class II disparity, tolerance to
      the Kb skin graft was not broken. Finally, direct evidence could be obtained for
      the avidity model of thymic epithelium-induced negative selection, using Kb
      specific T-cell receptor (TCR) transgenic mice. Thymic epithelium-grafted TCR
      transgenic mice showed a selective deletion of those CD8+ T cells with the
      highest density of the clonotypic TCR. These cells presumably represent the T
      cells with the highest avidity for Kb. We conclude that split tolerance induced
      by thymic epithelium was mediated by the deletion of those CD8+ T lymphocytes
      that have the highest avidity for antigen.

PMID- 7568233
TI  - Functional haplodiploidy: a mechanism for the spread of insecticide resistance in
      an important international insect pest.
AB  - The coffee berry borer, Hypothenemus hampei, is the most important insect pest of
      coffee worldwide and has an unusual life history that ensures a high degree of
      inbreeding. Individual females lay a predominantly female brood within individual
      coffee berries and because males are flightless there is almost entirely full sib
      mating. We investigated the genetics associated with this interesting life
      history after the important discovery of resistance to the cyclodiene type
      insecticide endosulfan. Both the inheritance of the resistance phenotype and the
      resistance-associated point mutation in the gamma-aminobutyric acid receptor gene
      Rdl were examined. Consistent with haplodiploidy, males failed to express and
      transmit paternally derived resistance alleles. Furthermore, while cytological
      examination revealed that males are diploid, one set of chromosomes was
      condensed, and probably nonfunctional, in the somatic cells of all males
      examined. Moreover, although two sets of chromosomes were present in primary
      spermatocytes, the chromosomes failed to pair before the single meiotic division,
      and only one set was packaged in sperm. Thus, the coffee berry borer is
      "functionally" haplodiploid. Its genetics and life history may therefore
      represent an interesting intermediate step in the evolution of true
      haplodiploidy. The influence of this breeding system on the spread of insecticide
      resistance is discussed.

PMID- 7568234
TI  - 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate
      aminotransferase express plasma membrane fatty acid-binding protein and saturable
      fatty acid uptake.
AB  - To explore the relationship between mitochondrial aspartate aminotransferase
      (mAspAT; EC 2.6.1.1) and plasma membrane fatty acid-binding protein (FABPpm) and
      their role in cellular fatty acid uptake, 3T3 fibroblasts were cotransfected with
      plasmid pMAAT2, containing a full-length mAspAT cDNA downstream of a Zn(2+)
      inducible metallothionein promoter, and pFR400, which conveys methotrexate
      resistance. Transfectants were selected in methotrexate, cloned, and exposed to
      increasing methotrexate concentrations to induce gene amplification. Stably
      transfected clones were characterized by Southern blotting; those with highest
      copy numbers of pFR400 alone (pFR400) or pFR400 and pMAAT2 (pFR400/pMAAT2) were
      expanded for further study. [3H]Oleate uptake was measured in medium containing
      500 microM bovine serum albumin and 125-1000 microM total oleate (unbound oleate,
      18-420 nM) and consisted of saturable and nonsaturable components. pFR400/pMAAT2
      cells exhibited no increase in the rate constant for nonsaturable oleate uptake
      or in the uptake rate of [14C]octanoate under any conditions. By contrast, Vmax
      (fmol/sec per 50,000 cells) of the saturable oleate uptake component increased
      3.5-fold in pFR400/pMAAT2 cells compared to pFR400, with a further 3.2-fold
      increase in the presence of Zn2+. Zn2+ had no effect in pFR400 controls (P >
      0.5). The overall increase in Vmax between pFR400 and pFR400/pMAAT2 in the
      presence of Zn2+ was 10.4-fold (P < 0.01) and was highly correlated (r = 0.99)
      with expression of FABPpm in plasma membranes as determined by Western blotting.
      Neither untransfected 3T3 nor pFR400 cells expressed cell surface FABPpm
      detectable by immunofluorescence. By contrast, plasma membrane immunofluorescence
      was detected in pFR400/pMAAT2 cells, especially if cultured in 100 microM Zn2+.
      The data support the dual hypotheses that mAspAT and FABPpm are identical and
      mediate saturable long-chain free fatty acid uptake.

PMID- 7568232
TI  - Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR
      gamma and C/EBP alpha.
AB  - Skeletal muscle and adipose tissue development often has a reciprocal
      relationship in vivo, particularly in myodystrophic states. We have investigated
      whether determined myoblasts with no inherent adipogenic potential can be induced
      to transdifferentiate into mature adipocytes by the ectopic expression of two
      adipogenic transcription factors, PPAR gamma and C/EBP alpha. When cultured under
      optimal conditions for muscle differentiation, murine G8 myoblasts expressing
      PPAR gamma and C/EBP alpha show markedly reduced levels of the myogenic basic
      helix-loop-helix proteins MyoD, myogenin, MRF4, and myf5 and are completely
      unable to differentiate into myotubes. Under conditions permissive for
      adipogenesis including a PPAR activator, these cells differentiate into mature
      adipocytes that express molecular markers characteristic of this lineage. Our
      results demonstrate that a developmental switch between these two related but
      highly specialized cell types can be controlled by the expression of key
      adipogenic transcription factors. These factors have an ability to inhibit
      myogenesis that is temporally and functionally separate from their ability to
      stimulate adipogenesis.

PMID- 7568235
TI  - The human and simian immunodeficiency virus envelope glycoprotein transmembrane
      subunits are palmitoylated.
AB  - The envelope proteins of human immunodeficiency virus (HIV) and simian
      immunodeficiency virus (SIV) were found to be modified by fatty acylation of the
      transmembrane protein subunit gp41. The precursor gp160 was also palmitoylated
      prior to its cleavage into the gp120 and gp41 subunits. The palmitic acid label
      was sensitive to treatment with hydroxylamine or 2-mercaptoethanol, indicating
      that the linkage is through a thioester bond. Treatment with cycloheximide did
      not prevent the incorporation of [3H]palmitic acid into the HIV envelope protein,
      indicating that palmitoylation is a posttranslation modification. In contrast to
      other glycoproteins, which are palmitoylated at cysteine residues within or close
      to the membrane-spanning hydrophobic domain, the palmitoylation of the HIV-1
      envelope proteins occurs on two cysteine residues, Cys-764 and Cys-837, which are
      59 and 132 amino acids, respectively, from the proposed membrane-spanning domain
      of gp41. Sequence comparison revealed that one of these residues (Cys-764) is
      conserved in the cytoplasmic domains of almost all HIV-1 isolates and is located
      very close to an amphipathic region which has been postulated to bind to the
      plasma membrane.

PMID- 7568238
TI  - Enhanced conformational sampling in Monte Carlo simulations of proteins:
      application to a constrained peptide.
AB  - A Monte Carlo simulation method for globular proteins, called extended-scaled
      collective-variable (ESCV) Monte Carlo, is proposed. This method combines two
      Monte Carlo algorithms known as entropy-sampling and scaled-collective-variable
      algorithms. Entropy-sampling Monte Carlo is able to sample a large
      configurational space even in a disordered system that has a large number of
      potential barriers. In contrast, scaled-collective-variable Monte Carlo provides
      an efficient sampling for a system whose dynamics is highly cooperative. Because
      a globular protein is a disordered system whose dynamics is characterized by
      collective motions, a combination of these two algorithms could provide an
      optimal Monte Carlo simulation for a globular protein. As a test case, we have
      carried out an ESCV Monte Carlo simulation for a cell adhesive Arg-Gly-Asp
      containing peptide, Lys-Arg-Cys-Arg-Gly-Asp-Cys-Met-Asp, and determined the
      conformational distribution at 300 K. The peptide contains a disulfide bridge
      between the two cysteine residues. This bond mimics the strong geometrical
      constraints that result from a protein's globular nature and give rise to highly
      cooperative dynamics. Computation results show that the ESCV Monte Carlo was not
      trapped at any local minimum and that the canonical distribution was correctly
      determined.

PMID- 7568237
TI  - Platelet-derived growth factor stimulates the secretion of hyaluronic acid by
      proliferating human vascular smooth muscle cells.
AB  - Total glycans from the cell layer and the culture medium of human vascular smooth
      muscle cells (VSMC) that had been cultivated in the presence of platelet-derived
      growth factor (PDGF) were isolated and purified by gel filtration after Pronase
      and DNase digestion and alkaliborohydride treatment. Measurements of the content
      of neutral hexoses and uronic acids revealed that PDGF stimulates total glycan
      synthesis by proliferating VSMC in a linear fashion from 24 h to 72 h of
      incubation. In contrast, total glycan synthesis by human fibroblasts, epithelial
      cells, or endothelial cells was not affected by PDGF, indicating cell-type
      specificity. Chemical, biochemical, and enzymological characterization of the
      total glycans synthesized by VSMC showed that PDGF stimulates the secretion of a
      340-kDa glycan molecule in a time-dependent manner from 24 h to 72 h. This
      molecule is highly acidic, shares a common structure with hyaluronic acid, and
      exhibits a potent antiproliferative activity on VSMC. These results suggest that
      VSMC in response to PDGF are capable of controlling their own growth and
      migration by the synthesis of a specific form of hyaluronic acid with
      antiproliferative potency, which may be involved in the regulation of the local
      inflammatory responses associated with atherosclerosis.

PMID- 7568240
TI  - Evidence that the pathway of disulfide bond formation in Escherichia coli
      involves interactions between the cysteines of DsbB and DsbA.
AB  - Disulfide bond formation is catalyzed in the periplasm of Escherichia coli. This
      process involves at least two proteins: DsbA and DsbB. Recent evidence suggests
      that DsbA, a soluble periplasmic protein directly catalyzes disulfide bond
      formation in proteins, whereas DsbB, an inner membrane protein, is involved in
      the reoxidation of DsbA. Here we present direct evidence of an interaction
      between DsbA and DsbB. (Kishigami et al. [Kishigami, S., Kanaya, E., Kikuchi, M.
      & Ito, K. (1995) J. Biol. Chem. 270, 17072-17074] have described similar
      findings.) We isolated a dominant negative mutant of dsbA, dsbAd, where Cys-33 of
      the DsbA active site is changed to tyrosine. Both DsbAd and DsbA are able to form
      a mixed disulfide with DsbB, which may be an intermediate in the reoxidation of
      DsbA. This complex is more stable with DsbAd. The dominance can be suppressed by
      increasing the production of DsbB. By using mutants of DsbB in which one or two
      cysteines have been changed to alanine, we show that only Cys-104 is important
      for complex formation. Therefore, we suggest that in vivo, reduced DsbA forms a
      complex with DsbB in which Cys-30 of DsbA is disulfide-bonded to Cys-104 of DsbB.
      Cys-104 is rapidly replaced by Cys-33 of DsbA to generate the oxidized form of
      this protein.

PMID- 7568236
TI  - Recruitment of hepatocyte nuclear factor 4 into specific intranuclear
      compartments depends on tyrosine phosphorylation that affects its DNA-binding and
      transactivation potential.
AB  - Hepatocyte nuclear factor 4 (HNF-4) is a prominent member of the family of liver
      enriched transcription factors, playing a role in the expression of a large
      number of liver-specific genes. We report here that HNF-4 is a phosphoprotein and
      that phosphorylation at tyrosine residue(s) is important for its DNA-binding
      activity and, consequently, for its transactivation potential both in cell-free
      systems and in cultured cells. Tyrosine phosphorylation did not affect the
      transport of HNF-4 from the cytoplasm to the nucleus but had a dramatic effect on
      its subnuclear localization. HNF-4 was concentrated in distinct nuclear
      compartments, as evidenced by in situ immunofluorescence and electron microscopy.
      This compartmentalization disappeared when tyrosine phosphorylation was inhibited
      by genistein. The correlation between the intranuclear distribution of HNF-4 and
      its ability to activate endogenous target genes demonstrates a phosphorylation
      signal-dependent pathway in the regulation of transcription factor activity.

PMID- 7568241
TI  - Direct observation of disordered regions in the major histocompatibility complex
      class II-associated invariant chain.
AB  - Invariant chain (Ii) is a trimeric membrane protein which binds and stabilizes
      major histocompatibility complex class II heterodimers in the endoplasmic
      reticulum and lysosomal compartments of antigen-presenting cells. In concert with
      an intracellular class II-like molecule, HLA-DM, Ii seems to facilitate loading
      of conventional class II molecules with peptides before transport of the class II
      peptide complex to the cell surface for recognition by T cells. The interaction
      of Ii with class II molecules is thought to be mediated in large part through a
      region of 24 amino acids (the class II-associated Ii peptide, CLIP) which binds
      as a cleaved moiety in the antigenic peptide-binding groove of class II molecules
      in HLA-DM-deficient cell lines. Here we use nuclear magnetic resonance techniques
      to demonstrate that a soluble recombinant Ii ectodomain contains significant
      disordered regions which probably include CLIP.

PMID- 7568239
TI  - Characterization and localization of the cytoplasmic dynein heavy chain in
      Aspergillus nidulans.
AB  - Migration of nuclei throughout the mycelium is essential for the growth and
      differentiation of filamentous fungi. In Aspergillus nidulans, the nudA gene,
      which is involved in nuclear migration, encodes a cytoplasmic dynein heavy chain.
      In this paper we use antibodies to characterize the Aspergillus cytoplasmic
      dynein heavy chain (ACDHC) and to show that the ACDHC is concentrated at the
      growing tip of the fungal mycelium. We demonstrate that four temperature
      sensitive mutations in the nudA gene result in a striking decrease in ACDHC
      protein. Cytoplasmic dynein has been implicated in nuclear division in animal
      cells. Because the temperature-sensitive nudA mutants are able to grow slowly
      with occasional nuclei found in the mycelium and are able to undergo nuclear
      division, we have created a deletion/disruption nudA mutation and a tightly
      downregulated nudA mutation. These mutants exhibit a phenotype very similar to
      that of the temperature-sensitive nudA mutants with respect to growth, nuclear
      distribution, and nuclear division. This suggests that there are redundant backup
      motor proteins for both nuclear migration and nuclear division.

PMID- 7568244
TI  - Le symposium Lavoisier. [The Lavoisier symposium].

PMID- 7568243
TI  - Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from
      adult human liver.

PMID- 7568242
TI  - Mutant oocytic low density lipoprotein receptor gene family member causes
      atherosclerosis and female sterility.
AB  - The so-called very low density lipoprotein receptors (VLDLRs) are related to the
      LDLR gene family. So far, naturally occurring mutations have only been described
      for the prototype LDLR; in humans, they cause familial hypercholesterolemia. Here
      we describe a naturally occurring mutation in a VLDLR that causes a dramatic
      abnormal phenotype. Hens of the mutant restricted-ovulator chicken strain carry a
      single mutation, lack functional oocyte receptors, are sterile, and display
      severe hyperlipidemia with associated premature atherosclerosis. The mutation
      converts a cysteine residue into a serine, resulting in an unpaired cysteine and
      greatly reduced expression of the mutant avian VLDLR on the oocyte surface.
      Extraoocytic cells in the mutant produce higher than normal amounts of a
      differentially spliced form of the receptor that is characteristic for somatic
      cells but absent from germ cells.

PMID- 7568245
TI  - Fuel selection, muscle fibre.
AB  - The fuel selection of muscle fibres at rest is dependent on substrate
      availability. Increased lipid availability results in an increase citrate
      concentration with inhibition of glycolysis. Fat utilization also increases the
      concentration ratio acetyl-CoA:CoASH, with inhibition of PDH transformation to
      the active form. The result is an inhibition of carbohydrate utilization in
      conformity with the classical glucose-fatty acid style. During exercise fuel
      selection is dependent on the intensity of exercise, the recruitment pattern of
      fibre type and the availability of fuels. During exercise at maximum intensity
      the main fuels are PCr and muscle glycogen, the highest energy release occurring
      with type II fibres. At exercise intensities between 70 and 100% VO2max
      carbohydrate is the main fuel after the intake of normal mixed or carbohydrate
      rich diets. No inhibition of PDHa formation was observed by increased
      concentration ratio acetyl-CoA:CoASH during the exercise, but the activation and
      transport of fatty-acyl groups from NEFA may be inhibited by a decrease in the
      concentration of CoASH. This mechanism may limit the contribution of fat to
      metabolism during exercise at intensities above 60% VO2max, after an intake of
      carbohydrate-rich diets. After carbohydrate starvation or an infusion of a fat
      emulsion, there was a substantial increase in the utilization of fat which, after
      the infusion, was concomitant with a high PDHa and a high lactate production.
      This is thought to be due to a decrease in glycolysis and in the catalytic
      activity of PDHa, especially in type I fibres, while lactate production continues
      in type II fibres. When exercise intensities fall below 60% VO2max, fat becomes
      the dominant fuel during prolonged exercise. At the same time the recruitment
      pattern is shifted toward type I fibres which have the lowest activation
      threshold and the highest oxidative capacity.

PMID- 7568246
TI  - Fuel selection at the level of mitochondria in mammalian tissues.

PMID- 7568249
TI  - Organ fuel selection: brain.
AB  - The brain's first choice for a metabolic fuel is glucose. In times of glucose
      lack, the brain can metabolize ketone bodies and lactate if they are available
      and by maintaining its metabolism, apparently, it also maintains its function.
      Brain metabolism of amino acid appears to be dictated by plasma levels, but the
      possibility that amino acids can support cerebral function during hypoglycaemia
      has not yet been investigated.

PMID- 7568248
TI  - Hepatic fuel selection.

PMID- 7568247
TI  - Muscle fuel selection: effect of exercise and training.

PMID- 7568250
TI  - Metabolic fuel selection by intestinal epithelium.

PMID- 7568252
TI  - Fuel selection in white adipose tissue.

PMID- 7568251
TI  - Substrate selection and oxygen uptake by the lactating mammary gland.

PMID- 7568253
TI  - The human epidermis.

PMID- 7568255
TI  - General integration and regulation of metabolism at the organ level.

PMID- 7568254
TI  - Fuel selection by the kidney: adaptation to starvation.

PMID- 7568256
TI  - Fatty acid transport and fatty acid-binding proteins.

PMID- 7568257
TI  - Whole-body fuel selection in ruminants: nutrient supply and utilization by major
      tissues.

PMID- 7568259
TI  - Feeding, fasting and starvation: factors affecting fuel utilization.

PMID- 7568258
TI  - Nutrient effects: post-absorptive interactions.

PMID- 7568260
TI  - What determines fuel selection in relation to exercise?

PMID- 7568261
TI  - Whole-body fuel selection: 'reproduction'.

PMID- 7568262
TI  - Comparative studies on programmes for management of energy supply: torpor, pre
      winter fattening and migration.

PMID- 7568263
TI  - Metabolic fuel selection: general integration at the whole-body level.

PMID- 7568264
TI  - Fuel selection in brown adipose tissue.

PMID- 7568265
TI  - Cellular aspects of fuel mobilization and selection in white adipocytes.

PMID- 7568266
TI  - Fuel utilization by cells of the immune system.

PMID- 7568267
TI  - Fuel selection in intestinal cells.

PMID- 7568268
TI  - Energy substrates for the rumen epithelium.

PMID- 7568270
TI  - Bootstrap estimated uncertainty of the dominant Lyapunov exponent for Holarctic
      microtine rodents.
AB  - The dominant Lyapunov exponent, as estimated from time series using the Jacobian
      based method, is often used for indicating whether the underlying dynamic system
      is chaotic or not. The Jacobian-based method together with Response Surface
      Methodology has been suggested as a method for detecting chaotic dynamics in
      ecological time series. Besides pointing out that this may not be an appropriate
      method, we report on estimates of the uncertainty in the estimates of the
      dominant Lyapunov exponent. For this purpose, we have used time series data on
      Holarctic microtines. On the basis of our analyses, we are unable to find general
      evidence for chaotic dynamics in northern microtine populations (north of 60
      degrees N) as recently suggested in the ecological literature. It seems, however,
      that the dynamic properties of the northern and southern populations are
      different. These patterns are supported by testing for nonlinearity.

PMID- 7568269
TI  - Potential impact of low efficacy HIV-1 vaccines in populations with high rates of
      infection.
AB  - A safe and effective HIV vaccine to prevent infection and/or to moderate disease
      is urgently needed. Research progress has been slower than anticipated for a
      variety of reasons including uncertainty over which immunogen to use (i.e.
      recombinant subunit envelope proteins or whole HIV-1 products), confusion on
      which immunological markers best correlate with protection, the relevance of the
      HIV-1 chimpanzee model to infection in humans and the significance of the rapid
      evolution of HIV-1, with different clades of the virus emerging in different
      parts of the world. However, what some would interpret as encouraging results,
      from Phase I and II trials of recombinant envelope glycoprotein vaccines, have
      raised the question of whether the time is right to start Phase III trials in
      humans with immunogens that may have low to moderate efficacy. By using
      mathematical models and data from epidemiological studies, we examine the
      potential impact of such vaccines within heterosexual communities with high rates
      of infection. Analyses suggest that it will be difficult to block HIV-1
      transmission even with very high levels of mass vaccination. The cost of
      sustaining high levels of herd immunity with a vaccine of short protection
      duration is likely to be high. However, assessments of impact over the long
      duration of an HIV-1 epidemic indicate that many cases of HIV infection and
      associated mortality can be prevented by immunogens with efficacy of 50% or less
      and a five year protection duration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568271
TI  - Mitochondrial DNA phylogeny and sequential colonization of Canary Islands by
      darkling beetles of the genus Pimelia (Tenebrionidae).
AB  - Fifteen species of the darkling beetle genus Pimelia (Tenebrionidae: Coleoptera)
      have been sequenced for a 365 b.p. portion of the mitochondrial Cytochrome
      Oxidase I gene. Thirteen of these are endemic species inhibiting the Canarian
      archipelago in the Atlantic and the other two are continental conspecifics. This
      data set has been phylogenetically analysed by maximum parsimony and distance
      approaches and the resulting trees used to deduce sequential interisland
      colonization. This suggests patterns compatible with the geological dating of the
      islands, but with increasing uncertainty when older events are considered. A
      colonization sequence from Fuerteventura to Tenerife followed by Tenerife to Gran
      Canarian and La Gomera, and from the latter to La Palma and then to El Hierro is
      proposed for the genus. A relatively recent secondary colonization from Gran
      Canaria to Gomera is deduced.

PMID- 7568272
TI  - The input-output relations of skeletal muscle.
AB  - We used three approaches to determine the stimulation patterns that maximize the
      isometric force-time integral per impulse (FTIpP) available from tibialis
      anterior muscles of the rabbit. Initially the interval between two pulses was
      fixed at the value that gave the maximum force-time integral, and successive
      pulses were added at intervals that maximized the FTIpP. We checked this
      iterative approach by a second method, in which a computer-generated protocol was
      used to deliver randomized bursts to the muscles. These experiments confirmed
      that optimal stimulation patterns for fast muscles consisted of an initial high
      frequency portion followed by a train of impulses at a lower frequency. However,
      for muscles that had been stimulated chronically at a constant low frequency, an
      initial high-frequency portion conferred no advantage. In a third set of
      experiments we used constant-frequency bursts to generate contour surfaces that
      represented the dependence of FTIpP on the frequency and number of impulses. The
      results agreed with those from the earlier methods. We conclude that optimized
      patterns have potential for clinical use, but their value will depend strongly on
      the activation characteristics of the stimulated muscle.

PMID- 7568274
TI  - Coinfection and the evolution of parasite virulence.
AB  - Analyses of the selection pressures acting on parasite virulence are made more
      complicated when individual hosts can simultaneously harbour many different
      strains or genotypes of a parasite. Here we explore the evolutionary dynamics of
      host-parasite associations in which individual hosts can be coinfected with many
      different parasite strains. (We take coinfection to mean that each strain
      transmits at a rate unaffected by the presence of others in the same host.) This
      study thus represents the opposite extreme to our earlier work on superinfection
      in which there is a dominance hierarchy such that only the most virulent strain
      present in a host is transmitted. For highly diverse populations of parasite
      strains, we find that such coinfection leads to selection for strains whose
      virulence-levels lie in a relatively narrow band close to the maximum consistent
      with the parasite's basic preproductive ratio, R0, exceeding unity.

PMID- 7568273
TI  - A test for adaptive change in DNA sequences controlling transcription.
AB  - Spatial and temporal differences in gene expression in early development result
      from the interaction of transcription factors with enhancer and silencer
      sequences in DNA. The evolution of the developmental process thus involves
      changes in the DNA sequences that bind transcription factors. Here we advocate a
      non-parametric statistical test-comparing levels of polymorphism and fixed
      substitutions between species -to look for evidence of adaptive evolution in
      sequences controlling gene expression. The test is illustrated by DNA sequence
      changes in the proximal part of the 'zebra' elements in the fushi terazu gene of
      the Drosophila melanogaster species group, which yield significant evidence for
      adaptive substitutions. (This is despite highly significant evidence that all
      parts of the sequence have been subject to strong selective constraint). The test
      can be applied generally to investigate adaptive evolution in the control of gene
      expression.

PMID- 7568276
TI  - Intermittency and transient chaos from simple frequency-dependent selection.
AB  - Frequency-dependent selection is an important determinant of the evolution of
      gametophytic self-incompatibility systems in plants, aposematic (warning) and
      cryptic coloration, systems of mimicry, competitive interactions among members of
      a population, mating preferences, predator-prey and host-parasite interactions,
      aggression and other behavioural traits. Past theoretical studies of frequency
      dependent selection have shown it to be a plausible mechanism for the maintenance
      of genetic variability in natural populations. Here, through an analysis of a
      simple deterministic model for frequency-dependent selection, we demonstrate that
      complex dynamic behaviour is possible under a broad range of parameter values. In
      particular we show that the model exhibits not only cycles and chaos but also,
      for a more restricted set of parameters, transient chaos and intermittency:
      alterations between an apparently deterministic behaviour and apparently chaotic
      fluctuations. This behaviour, which has not been stressed within the population
      genetics literature, provides an explanation for erratic dynamics of gene
      frequencies.

PMID- 7568275
TI  - Full sequence and characterization of two insect defensins: immune peptides from
      the mosquito Aedes aegypti.
AB  - We report the complete amino acid sequence and biological activity of two immune
      peptides, from the yellow fever mosquito Aedes aegypti, that are induced in
      response to infection. Both peptides display biological activity against the Gram
      positive microbe Micrococcus luteus and substantial sequence homology to insect
      defensins, small heat-stable, antibiotic peptides previously described from
      several non-vector insects. These mosquito peptides, designated Ae. aegypti
      defensins A and B, are isoforms. Defensin B is the most abundant antibacterial
      peptide in this species whereas defensin A is much less abundant and carries two
      amino acid substitutions compared to defensin B, making it more basic in
      character. Apparent convergence between isoforms from Ae. aegypti and the
      fleshfly Phormia terranovae is discussed. The synergistic activity previously
      described between Ae. aegypti immune haemolymph and lysozyme is not caused by
      these peptides because synergy occurred only at concentrations far outside the
      physiological range seen in Ae. aegypti.

PMID- 7568277
TI  - Interpretation of 'quantal' peaks in distributions of evoked synaptic
      transmission at central synapses.
AB  - At some synaptic connections in the central nervous system, amplitude
      distributions of evoked synaptic currents exhibit surprisingly sharp and
      regularly spaced peaks. At these connections, detailed analysis of the peaks has
      led to the proposal that the 'quantal' synaptic current displays very little
      variability, not only at a release site, but also between release sites. In this
      study the latter hypothesis has been tested using simulations of evoked
      transmission. In contrast with previous conclusions, these simulations
      demonstrate that the experimental observation of regularly spaced peaks in
      amplitude distributions of synaptic currents is compatible with large underlying
      differences in the synaptic current amplitudes between release sites. The
      simulations also reveal that quantal analysis based entirely on the observation
      and analysis of regularly spaced peaks in evoked synaptic current amplitude
      distributions, cannot be used with confidence to estimate presynaptic release
      probabilities, 'quantal' current amplitudes at each release site, or the total
      number of available release sites. This problem may be a confounding factor in
      determining whether pre- or postsynaptic changes underlie alterations in synaptic
      efficacy, such as occurs during long term potentiation.

PMID- 7568278
TI  - Subunit-dependent assembly of inward-rectifier K+ channels.
AB  - Inward-rectifier, G-protein-regulated and ATP-dependent K+ channels form a novel
      gene family of related proteins which share two transmembrane segments as a
      common structural feature. These K+ channels are only distantly related to the
      voltage-gated Shaker-type K+ channels comprising six transmembrane segments.
      Although the quaternary structure of voltage-gated K+ channels has been
      extensively studied in the past, little is known about subunit assembly of inward
      rectifier K+ channels. Differential sensitivity of inward-rectifier K+ channels
      to voltage-dependent pore block by spermine was used to analyse subunit assembly.
      It is shown that inward-rectifier K+ channel proteins are composed of four
      subunits whose assembly obeys the rules of a binomial distribution. 'Strong' and
      'mild' inward-rectifier K+ channel subunits (BIR10 and ROMK1) which are co
      expressed in individual auditory hair cells form hetero-tetramers. Distribution
      of these hetero-tetramers, however, is not binomial. Hetero- and homo-oligomeric
      channels form with similar probabilities resulting in independent channel
      populations with distinct functional properties.

PMID- 7568279
TI  - Expression of gamma-glutamylcysteine synthetase in the liver of copper-deficient
      rats.
AB  - Copper deficiency in rats increases hepatic glutathione concentration. The
      present study was undertaken to determine the biochemical and molecular basis for
      the glutathione elevation. Weanling Sprague-Dawley rats were fed a purified diet
      deficient in copper (0.4 micrograms/g diet) or one containing adequate copper
      (5.7 micrograms/g diet) for 4 weeks. Hepatic glutathione concentration, the
      activity of the rate-limiting enzyme in glutathione biosynthesis, gamma
      glutamylcysteine synthetase (gamma-GCS) and the relative amount of mRNA for the
      enzyme were determined. Hepatic glutathione concentration in copper-deficient
      rats was significantly elevated (6.6 vs 5.6 mumol/g). The activity of hepatic
      gamma-GCS was 1.6 times higher in the copper-deficient than in the copper
      adequate rats (58.0 vs 35.9 nmol NADH/min.mg protein). The steady-state amount of
      mRNA for gamma-GCS was increased 5-fold in the copper-deficient rat liver. The
      findings demonstrate that the elevated hepatic glutathione concentration in
      copper-deficient rats results from upregulation of gamma-GCS activity. This study
      provides further understanding of changes in hepatic glutathione metabolism
      induced by copper deficiency.

PMID- 7568281
TI  - Influence of thyroxine and thyroxine with growth hormone and prolactin on
      splenocyte subsets and on the expression of interleukin-2 and prolactin receptors
      on splenocyte subsets of Snell dwarf mice.
AB  - A number of immune parameters were examined in Snell dwarf mice and compared with
      normal littermates. The number of splenocytes per gram of body weight were
      significantly decreased in dwarf animals, and the decrease was distributed
      throughout the CD4, CD8, B220, and MAC-1 subsets. The percentage of CD4 and CD8
      splenocytes was markedly increased, and the percentage of B220 and MAC-1
      splenocytes markedly decreased, in dwarf animals. In addition, the percentage of
      splenocyte T cells constitutively expressing interleukin-2 (IL-2) receptors and
      prolactin (PRL) receptors was decreased, with the CD4 subset presenting the most
      dramatic effect. The effects of replacing the hormones deficient in the Snell
      dwarf mouse (i.e., growth hormone [GH], prolactin [PRL], and thyroxine [T4] on
      the above immune parameters were also examined. The administration of T4 alone
      for 10 days corrected the defect in splenocyte cell numbers per grams body weight
      for both the CD4 and CD8 subsets, but only partially corrected the defect for the
      B220 and MAC-1 subsets. The addition of rbGH and rbPRL for the last 3 days of T4
      injection had little additive effect on the number of CD4 and CD8 cells but
      increased the number of B220 and MAC-1 subsets to values comparable to those of
      normal animals on the basis of body weight. The decrease in the percentage of CD4
      splenocytes in dwarf animals constitutively expressing IL-2R was partially
      corrected by T4 injection and completely corrected by the addition of rbGH and
      rbPRL for the last 3 days. The decrease in CD4 splenocytes constitutively
      expressing PRLR was partially corrected by T4 injection alone and the addition of
      rbGH and rPRL resulted in percentages comparable to that of normal animals. The
      results indicate that Snell dwarf animals are deficient in immune parameters and
      that the administration of the hormones lacking in this animal can correct the
      deficiencies.

PMID- 7568280
TI  - Alterations of rat brain peptidylglycine alpha-amidating monooxygenase and other
      cuproenzyme activities following perinatal copper deficiency.
AB  - Perinatal copper (Cu) deficiency was studied in month-old female and male Sprague
      Dawley rat offspring to investigate regional changes in brain cuproenzymes.
      Offspring of dams given the low Cu treatment beginning at Day 7 of gestation
      exhibited signs characteristic of Cu deficiency including a 70% reduction in
      liver Cu levels compared with Cu-adequate controls. Compared with Cu-adequate
      rats, Cu-deficient rats had lower activities of the cuproenzymes peptidylglycine
      alpha-amidating monooxygenase (PAM), cytochrome c oxydase (CCO), and Cu,Zn
      superoxide dismutase (SOD) in all six brain regions studied. Apparent activity of
      dopamine-beta-monooxygenase (DBM) was higher in all regions from Cu-deficient
      compared with Cu-adequate rats. Activity of the selenoenzyme glutathione
      peroxidase (GPX) was not greatly altered in brain by Cu deficiency. Following 1
      month of Cu repletion, liver but not brain Cu levels were equivalent to control.
      Brain CCO activity was still lower in Cu-repleted female and male rats. PAM
      activity was still lower in cerebrum of Cu-repleted rats. DBM activity was no
      longer significantly elevated in the former Cu-deficient groups except for
      midbrain. SOD and GPX activity were equivalent between groups. PAM activity, in
      vitro, is lower in the brain following perinatal Cu deficiency and activity is
      slow to recover following nutritional supplementation with Cu. Perhaps
      neuropeptide maturation is compromised by Cu deficiency.

PMID- 7568282
TI  - Assessment of the primary adrenal cortical and pancreatic hormone basal levels in
      relation to plasma glucose and age in the unstressed Ames dwarf mouse.
AB  - Peripheral glucose concentrations in mammals are maintained within very narrow
      limits to provide a continuous, uninterrupted supply of this nutrient to tissues.
      Numerous factors have been shown to influence and/or regulate glucose levels. One
      such influence is growth hormone (GH) produced by the pituitary somatotrophs.
      Several animal models of hyposomatotropism are available in which GH secretion or
      actions are suppressed due to genetic abnormalities. One such model, the Ames
      dwarf mouse (df/df), has arisen from an autosomal recessive mutation in which GH
      , prolactin- (PRL), and thyroid-stimulating hormone (TSH)-producing cell types of
      the anterior pituitary fail to develop. The current investigation examined the
      effects of GH deficiency on glucose, insulin, and corticosterone levels using
      male and female df/df mice and their normal (Df/-) littermates. Additionally, old
      and young females of both genotypes were used to determine whether aging and GH
      deficiency interact to influence insulin, corticosterone or glucose levels in
      these animals. Plasma samples collected from unstressed animals (normal, df/df;
      young [5 months], old [17-19 months]; male, female) were used. Glucose levels
      were lower (P < 0.05) in df/df than in Df/- mice regardless of sex and age. A sex
      difference in Df/- animals was evident--young and old females had significantly
      lower levels of glucose when compared with young Df/- males. Plasma insulin was
      elevated (P < 0.05) in old df/df females compared with young df/df and Df/-
      females. Young Df/- males had the highest insulin levels compared with all
      genotype and age groups. This observation paralleled results from glucose
      measurements. Corticosterone levels were highest in young Df/- females and lowest
      in young Df/- males, with df/df animals falling between these values. Plasma
      corticosterone levels in old Df/- females did not differ from the values measured
      in dwarfs. The present findings indicate that glucose and factors affecting
      glucose levels are altered in the df/df mouse. These results provide new insights
      into the roles GH may play in glucose metabolism and perhaps also in adiposity
      which is a common characteristic of Df/- aged females from this line of mice.

PMID- 7568283
TI  - The induction of hepatic cytochrome P450 3A in rats: effects of age.
AB  - Liver microsomal cytochrome P450 3A (CYP3A) concentrations were evaluated by
      Western blots using specific antisera. Low levels of CYP3A protein were found in
      untreated animals. Dexamethasone (DX) treatment resulted in a significant
      induction of CYP3A. The induction was dose and time dependent. Addition of U486
      (a specific type II glucocorticoid receptor antagonist), but not spironolactone
      (a specific type I receptor antagonist) blocked the induction of CYP3A proteins
      by dexamethasone, suggesting a receptor-mediated mechanism. Concomitant
      administration of either actinomycin D or cyclohexamide, together with
      dexamethasone completely abolished the induction of CYP3A protein by
      dexamethasone, suggesting the requirement of both protein and RNA synthesis. A
      comparison of the inducibility of CYP3A protein by dexamethasone in rats from
      different age groups showed that the degree of increase was higher in the younger
      than in the older groups (e.g., 5 days versus adult). Thus, there is an
      attenuation in the responsiveness to dexamethasone induction of CYP3A proteins
      with age. Evaluation of the steady-state levels of CYP3A mRNA by Northern blots
      showed increases in mRNA following DX treatment in both young and old rats. The
      final level of CYP3A mRNA reached after DX treatment was higher in the pups than
      that found in similarly treated older rats. This decrease in responsiveness in
      older animals appeared to manifest at least in part of the pretranslational
      level.

PMID- 7568284
TI  - Relationship of inflammatory cytokines, growth hormone, and insulin-like growth
      factor-I to reduced performance during infectious disease.
AB  - Production of inflammatory cytokines and concentrations of growth hormone and
      insulin-like growth factor-I (IGF-I) were studied during experimental Escherichia
      coli mastitis to determine their potential involvement in reduced animal
      performance during infectious disease. During the first 10 to 14 hr after
      intramammary infusion of E. coli, bacteria multiplied to maximum levels of 10(4)
      10(9) cfu/ml of milk with no clinical signs of mastitis. A rapid and intense
      inflammatory response, characterized by udder swelling, increased bovine serum
      albumin (BSA) and somatic cell count (SCC) in milk of infected glands, and
      elevated rectal temperature and serum cortisol concentration, began at
      approximately 12 hr after challenge. Lactational performance was reduced greatly
      at 24 hr, and the maximal decrease averaged 76% and 63% among infected and
      uninfected glands, respectively, of challenged cows; three cows became
      temporarily agalactic in all glands. By 6 days, all cows had nearly or completely
      eliminated the E. coli, and milk production had partially recovered. Milk
      composition showed an initial decrease in fat percentage followed by an increase
      thereafter. Protein percentage was increased and lactose content was reduced
      during most of the mastitic episode. High concentrations of tumor necrosis factor
      (TNF) and interleukin-1 (IL-1) were detected in milk of infected glands, and
      their appearance preceded or coincided with development of the mammary
      inflammation, systemic reaction, and hypogalactia. Serum growth hormone
      concentration was higher among challenged cows, whereas serum IGF-I
      concentrations changed little during the mastitic episode. Concentrations of IGF
      I in milk whey increased from 5.0 to 12.2 ng/ml among infected glands and from
      4.4 to 8.5 ng/ml among contralateral, uninfected glands; IGF binding proteins
      also increased in the milk of infected glands. These data demonstrate that (i)
      reduced lactational performance is not caused by reduced concentrations of growth
      hormone or IGF-I and (ii) inflammatory cytokines are produced at a time
      consistent with a possible role in the inhibition of milk synthesis.

PMID- 7568286
TI  - Tissue distribution of alpha-tocopherol following dietary supplementation in the
      rat: effects of concomitant cholesterol feeding.
AB  - Vitamin E is a potent, naturally occurring, lipid-soluble antioxidant, which is
      reported to be protective against several disease processes, including coronary
      atherosclerosis. We have measured the alpha-tocopherol content of the aorta,
      liver, skeletal muscle, and kidney of rats fed one of the following diets for 10
      weeks: a normal control chow diet (i); or the same diet containing 1% cholesterol
      (ii); 0.5% vitamin E (iii); or 1% cholesterol plus 0.5% vitamin E (iv). The alpha
      tocopherol content of serum and tissue extracts was measured by HPLC using gamma
      tocopherol as an internal standard. Tissue and serum cholesterol content was
      measured using a cholesterol oxidase enzyme reagent kit. In all animals receiving
      the 1% cholesterol diet, serum cholesterol levels increased significantly (P <
      0.005). By the 10th week, mean serum alpha-tocopherol levels rose significantly
      in both groups of animals receiving dietary vitamin E supplements (P < 0.0001)
      compared with their respective control group. This was accompanied by a
      significant increase in the absolute alpha-tocopherol content of liver (8- to 9
      fold) and aorta (3- to 4-fold). The alpha-tocopherol content of renal and
      skeletal muscle tissue was raised 1- to 2-fold in both groups of rats on vitamin
      E supplements, however the increased attained significance only for the renal
      tissue. The aortic tissue alpha-tocopherol/cholesterol ratio was 4-fold higher in
      the rats receiving concomitant 1% cholesterol plus 0.5% vitamin E compared with
      animals receiving 1% cholesterol alone (P < 0.02), and was 5-fold higher in the
      rats receiving 0.5% vitamin E compared with those receiving control chow (P <
      0.01). These data suggest that dietary vitamin E supplementation results in a
      differential uptake of alpha-tocopherol, which may be dependent, in part, on
      selective lipoprotein particle accumulation.

PMID- 7568289
TI  - Lead alters growth and reduces angiotensin II receptor density of rat aortic
      smooth muscle cells.
AB  - Environmental lead (Pb2+) contributes a small but significant risk to human
      hypertension. It is postulated that the hypertensinogenic action of Pb2+ may be
      due, in part, to its direct action on vascular smooth muscle cells. To
      investigate this hypothesis, freshly isolated rat aortic smooth muscle (RASM)
      cells were propagated in defined media containing one of two Centers for Disease
      Control-based concentrations of Pb2+ (as lead citrate): 100 and 500 micrograms
      Pb2+/l (i.e., equivalent to 5.5 and 27.5 micrograms Pb2+/dl blood; designated 100
      RASM and 500-RASM). Control (CON-RASM) cells received sodium citrate. 500-RASM
      cells exhibited suppressed propagation and fell out of propagation synchrony with
      CON-RASM cells: when CON-RASM cell approached confluence (approximately 90%), 500
      RASM cell density was 6.4% that of CON-RASM cell density. By contrast, 100-RASM
      cells exhibited marked hyperplasia albeit this was not apparent until passage 3
      (p3). Overall, when p3-p6 CON-RASM cells approached confluence, 100-RASM cell
      density was 107.6% greater than CON-RASM cell density. The protein content of CON
      RASM and 100-RASM was not different, whereas that of 500-RASM cells was 29%
      greater than that of CON-RASM and 100-RASM cells. Phase-contrast microscopy
      revealed that 100 micrograms Pb2+/l converted normal spindle-shaped/ribbon-shaped
      RASM cells into less spread, cobblestone-shaped, neointimal-like cells.
      Immunocytochemical analysis revealed that 100-RASM cells lacked or had markedly
      fewer actin cables, characteristic of rapidly dividing cells. In addition, Pb(2+)
      treated RASM cells exhibited altered membrane fatty acyl composition with a trend
      towards an increase (by as much as 50%) in membrane arachidonic acid.
      Interestingly, hyperplastic 100-RASM cells exhibited a 70.6% reduction in
      angiotensin II (Ang II) receptor concentration whereas the concentrations of
      alpha 1- and beta-adrenergic and atrial natriuretic peptide (ANP) receptors were
      not affected. In addition, in experiments designed to control for Pb(2+)
      associated differences in RASM cell propagation, there was a concentration
      dependent decrease in Ang II receptor concentration: for 100 and 500 micrograms
      Pb2+/l, Ang II receptor concentration was decreased 39.6% and 65.5%,
      respectively. Thus, although Pb2+, depending on its concentration, had
      contrasting effects on RASM cell propagation, it had a consistent, concentration
      dependent inhibitory effect on Ang II receptor concentration. Recovery (r) from
      Pb2+ required at least two additional passages. At p71r the enhanced propagation
      (+54%) and reduced Ang II receptor concentration (-49%) of 100r-RASM cells
      persisted.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7568287
TI  - Transforming growth factor-alpha and epidermal growth factor activate mitogen
      activated protein kinase and its substrates in intestinal epithelial cells.
AB  - The signal transduction pathways of mitogenic stimuli in intestinal epithelial
      cells are not clearly understood. We report here a possible signaling pathway of
      two closely related agonists, transforming growth factor-alpha (TGF alpha) and
      epidermal growth factor (EGF). Both increase thymidine incorporation in the
      intestinal epithelial cell (IEC) line IEC-6. This increase is dose dependent and
      inhibited by the tyrosine kinase inhibitors genistein and tyrphostin. The
      addition of either TGF alpha or EGF to IEC-6 cells also stimulates the activities
      of the two forms of mitogen-activated protein kinase, p42erk2 MAPK and p44erk1
      MAPK, as evidenced by increased incorporation of radiolabeled phosphate in myelin
      basic protein. The main difference between the MAPK activity levels induced by
      the two agonists is in the intensity of the response. Maximum TGF alpha-induced
      stimulation of p42erk2 MAPK activity is 9-fold at 2 ng/ml, while maximum EGF
      stimulation is only 4.5-fold at 25 ng/ml. These doses correlated closely with the
      dose required for maximum thymidine incorporation. The activity of the 90-kDa
      ribosomal S6 kinase, a downstream substrate for activated MAPK, is also enhanced
      as evidenced by increased incorporation of radiolabeled phosphate in the rsk
      kinase substrate peptide in IEC-6 cells following stimulation with either TGF
      alpha or EGF. This increase correlates closely with the stimulus-induced increase
      in MAPK activity with respect to dose, but the time of increased activity is more
      prolonged, especially after EGF stimulation. TGF alpha induced the synthesis of
      both c-Fos and c-Myc, two nuclear substrates for MAPK, and increased c-fos and c
      myc message levels as well. However, c-Jun protein and c-jun mRNA were not
      induced. The increase in IEC-6 cell proliferation in response to TGF alpha and
      EGF stimulation may then be due, in part, to an increase in immediate early gene
      expression as a direct result of MAPK and RSK activation.

PMID- 7568288
TI  - Effects of prenatal ultrasound exposure on adult offspring behavior in the Wistar
      rat.
AB  - An ultrasound exposure tank was specifically designed for experimental bioeffects
      studies. Thirty-six pregnant rats were anesthetized, immersed to the axilla in a
      water tank, and exposed on Day 15, 17, and 19 of gestation. Twelve rats were
      exposed to 5.0 MHz pulsed ultrasound of effective pulse duration equal to
      approximately 0.170 microseconds, pulse repetition rate (PRF) 1 kHz, and a
      spatial peak, temporal peak intensity (lsptp) of 500 W/cm2, representing a
      clinically appropriate exposure level. The spatial peak pulse average (lsppa),
      spatial peak temporal average (lspta), and instantaneous maximum (lm) intensities
      were determined to be 100 W/cm2, 24 mW/cm2, and 230 W/cm2, respectively. The
      maximum rarefraction pressure, pr, was measured as 12.5 x 10(5) Pa, and the total
      power was 2.5 mW. Twelve other rats were exposed to 1500 W/cm2, lsptp, and 12
      were sham insonified. Since the focal area was about 0.05 cm2, computer
      controlled stepper motors moved the rats through the ultrasound field to ensure
      uniform exposure of the abdominal/pelvic region. Total exposure time was 35 min.
      A miniature thermocouple was implanted in a few rats to verify that no
      significant temperature increase took place due to exposure. A total of 278
      offspring were maintained until postnatal Day 60 when they were subjected to two
      of four behavioral tests in random order within sexes. The results indicate no
      consistently observed dose-related alterations in adult behavior due to prenatal
      fetal exposure to 5.0 MHz ultrasound below an intensity (lsptp) of 1500 W/cm2.

PMID- 7568285
TI  - Dynamics of prolactin secretion from diethylstilbestrol-induced rat prolactinoma
      tissue in vitro.
AB  - Experiments were performed to determine whether PRL secretion in the rat
      diethylstilbestrol (DES)-induced prolactinoma model is affected by the addition
      of thyrotropin-releasing hormone (TRH) and/or immunoneutralization of
      intrapituitary vasoactive intestinal polypeptide (VIP) in vitro. Male Fischer 344
      rats were implanted with either a 10 mg DES or placebo pellet 30 days prior to
      obtaining the anterior pituitary glands for perifusion. The anterior pituitaries
      were quartered and used in three different perifusion experiments. In Experiment
      I, placebo-treated tissue channels were perifused for 2 baseline hr followed
      consecutively by a 30-min exposure to 1:100 nonimmune rabbit serum (NRS), a 30
      min wash, and a final 30-min exposure to 10(-5) M TRH. Additional placebo
      channels were run as above except 1:100 VIP antiserum (AVIP) was substituted for
      NRS and AVIP was added to the TRH. In Experiment II, the same perifusion protocol
      was used as in Experiment I, except DES-induced tumor tissue was used instead of
      placebo tissue. Results from Experiment I and II reveal that AVIP significantly
      decreased PRL secretory rate in both DES and placebo groups. In the tumor group,
      both TRH alone and in the presence of AVIP significantly increased the PRL
      secretory rate. In Experiment III DES-induced tumor tissue channels were
      perifused with a similar protocol, except the concentrations of NRS and AVIP were
      increased to 1:10. Both NRS and AVIP significantly decreased PRL secretory rate;
      however, AVIP had a significantly greater effect than NRS. In this experiment,
      1:10 AVIP overcame the stimulatory effect of TRH. In conclusion, AVIP decreases
      and TRH increases, even in the presence of AVIP, PRL release in DES-induced
      prolactinoma tissue in vitro. Increasing the AVIP concentration 10-fold
      diminished the PRL-releasing action of TRH in the tumor tissue. These data
      suggested that PRL secretion is not autonomous in these prolactinomas and can be
      affected by exogenous TRH and partial immunoneutralization of endogenous VIP.

PMID- 7568290
TI  - Nitric oxide: a novel mediator of inflammation.

PMID- 7568292
TI  - [The professional secret: a deontological obligation].

PMID- 7568293
TI  - [Informed consent].

PMID- 7568291
TI  - [Cybernursing: computer networks at the service of the nurse].

PMID- 7568294
TI  - [The Canadian legislation regulating consent to a therapy].

PMID- 7568296
TI  - [Child welfare in Trieste during the 19th century].

PMID- 7568295
TI  - [Ethics and bioethics in the nursing profession].

PMID- 7568297
TI  - [An Italian nurse in Ruanda].

PMID- 7568298
TI  - [Rates for hospital services: general and technical aspects developed by the
      nursing profession].

PMID- 7568299
TI  - [The hospitalized diabetic: how the professional nurse can promote the
      educational momentum].

PMID- 7568300
TI  - Migraine.

PMID- 7568301
TI  - The hands-on specialist nurse in renal care.
AB  - Any level of qualified nurse can become a specialist practitioner. Specialist
      nurses bring an extended role and expanded knowledge to hands-on care. Clear
      guidelines and responsibilities are essential. Specialist nurses provide optimum
      care in a cost-effective way.

PMID- 7568302
TI  - Clinical supervision for nurses working with people with HIV/AIDS.
AB  - Nurses caring for people with HIV disease may have support and developmental
      needs related to knowledge, attitudes, stress and isolation. The potential
      benefits of supervision may be illustrated by exploring models that could meet
      the needs of nurses caring for people with HIV disease.

PMID- 7568305
TI  - Preventing and managing pressure sores in palliative care.
AB  - Pressure sore rates were addressed in a palliative care unit by undertaking risk
      assessment, monitoring wound status and introducing a dressing protocol. A
      systematic approach to pressure sores in palliative care resulted in a decrease
      in pressure sore rates in one hospice.

PMID- 7568303
TI  - Heparin lock practice in total parenteral nutrition.
AB  - Catheter occlusion can complicate parenteral feeding. Careful management can
      reduce the incidence of occlusion. Low-dose heparin lock is an effective
      preventive measure.

PMID- 7568304
TI  - Congenital talipes equinovarus.

PMID- 7568306
TI  - Raising awareness of patients' nutritional state.
AB  - Many patients are malnourished on admission to hospital. Many members of care
      staff are unaware of the nutritional status of their patients. Initial nursing
      assessment can be expanded to include a nutritional assessment. A
      multidisciplinary approach to nutritional assessment should be established.

PMID- 7568307
TI  - Implications of smoking bans in long-term care.
AB  - The physical benefits of smoking cessation are well established. In long-stay
      units, the mental and social well-being of the individual need to be considered.
      Privacy, self-esteem and a measure of control are important to long-stay clients.

PMID- 7568308
TI  - PREP profiles: creating and using learning opportunities.
AB  - PREP requires practitioners to demonstrate that they have completed the
      equivalent of five days' study activity over three years. This requirement
      commences from the first renewal of registration with the UKCC after April 1995.
      Study requirements may be fulfilled in many different ways, without necessarily
      spending time in formal classroom courses. Profile records should include
      outcomes, demonstrating the relevance of the study activity to the practitioner's
      work area.

PMID- 7568309
TI  - Devices for measuring blood glucose levels.
AB  - Monitoring blood glucose is as essential as ever. Technology has given real
      freedom to people with diabetes. The aim of diabetes management these days is
      simply to allow for a normal life. Nurses must keep abreast of all new
      developments.

PMID- 7568311
TI  - Achieving professional autonomy for nursing.
AB  - A profession's specific skills are supported by an organised and internally
      consistent body of knowledge. Through the introduction of the nursing process and
      'holism', nursing is striving to gain professional autonomy and an identity
      independent of medicine. The status of nursing cannot be raised without tackling
      the issue of gender.

PMID- 7568310
TI  - Innovation and the role of the change agent.
AB  - The implementation of change is a complex process, which requires a collaborative
      approach. Change agents need the flexibility to alter their role to suit local
      circumstances.

PMID- 7568313
TI  - [Enzyme tableting--questions on administration and stability].

PMID- 7568312
TI  - The relationship between nurse and patient.
AB  - Psychological care is hard to measure in terms of its practical effect upon the
      patient. Nursing priorities still appear to lie in 'getting the work done'. In
      order to provide a high level of psychological care for patients, a support
      system must be available for nurses. Support networks to evaluate and discuss
      care may provide the avenues through which to explore the effect emotional care
      has on patients.

PMID- 7568314
TI  - Thiophene congeners of morpholine and allylamine type antifungals--syntheses and
      biological activities.
AB  - A thiophene analogue 8 of the antifungal drug amorolfine (1) was prepared
      starting from the alcohol 5. In addition, congeners of naftifine, terbinafine and
      butenafine, in which the naphthalene ring is replaced by a branched thienylalkyl
      group, wee synthesized. Of the four drug analogues only compound 9, related to
      terbinafine, showed significant antifungal activity.

PMID- 7568315
TI  - Synthesis of some pyrido- and pyrazino-benzimidazole derivatives and their
      antifungal activity.
AB  - Some 2-aryl-4-hydroxypyrido[1,2-a]benzimidazole and 1-substituted 3-arylpyrazino
      [1,2-a]benzimidazole derivatives were synthesized using 1-(2-arylethan-2-on)-2
      acylbenzimidazole derivatives as starting materials. Antifungal activities of the
      compounds obtained were examined in vitro.

PMID- 7568316
TI  - Antitumor and immunosuppressive activity of Merbarone's analogues and
      arylidenehydrazinopyrimidines.
AB  - The synthesis of Merbarone's analogues, the 4-thio- or 4-oxo derivatives of 5
      carbamoyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine is described, starting from
      5-carboxy-6-methyl-2-oxo-4-thioxo-1,2,3,4-tetrahydropyrimidine+ ++. That was also
      used as staring material for synthesis of NCS624947 analogues, the 4
      arylidenehydrazino-5-carbamoylpyrimidines. The reduction of
      arylidenehydrazinopyrimidines with hydrogen on Pd/C was also performed. The
      obtained compounds were successfully tested for anticancer and immunomodulating
      activity.

PMID- 7568317
TI  - Quantitation of R- and S-propafenone and of the main metabolite in plasma.
AB  - Several methods for the determination of racemic propafenone or its enantiomers
      as well of the main metabolite R,S-5-hydroxypropafenone are known from the
      literature. The method described here enables the simple simultaneous
      quantification of R- and S-propafenone and of R,S-5-hydroxypropafenone in human
      plasma. The method is based on an HPLC separation using a Chiralpak AD column.
      High recovery rates (80-95%) were achieved by means of a liquid-liquid-extraction
      at pH 11 with dichloromethane as solvent. The separation on the chiral carrier
      were carried out with n-hexane/2-propanol; the addition of diethylamine is
      useful. The obtained capacity factors are k' = 2.36 for R-propafenone and k' =
      3.82 for S-propafenone. R,S-propanolol and R,S-metoprolol were used as internal
      standards. The method described can be used for pharmacokinetic trials in man
      with the following limits of quantitation: 10 ng/ml for R- and S-propafenone and
      20 ng/ml for R,S-5-hydroxypropafenone.

PMID- 7568318
TI  - Investigations into the mechanism of toxicity of lipopolysaccharide (LPS) in
      bovine aortic endothelial cells.
AB  - The cytotoxic effect of lipopolysaccharide (LPS) was examined on bovine aortic
      endothelial cell proliferation in vitro. These LPS-induced cytotoxicity (IC50 =
      20 ng/ml) was not inhibitable by substances regulating the formation of nitric
      oxide (NO). e.g. by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO
      synthesis, and by the glucocorticoid dexamethasone, an inhibitor of the induction
      of NO synthase. Also other substances which inhibit the generation or action of
      oxygen radicals, as glutathion and the xanthine oxidase inhibitor allopurinol did
      not prevent the cytotoxic effect of LPS. Only tyrphostin B46, an inhibitor of
      tyrosine kinase, attenuated the toxic LPS effect, suggesting that the LPS-induced
      cytotoxicity in bovine aortic endothelial cell cultures is mediated by a specific
      tyrosine kinase, and not by NO or oxygen radicals.

PMID- 7568320
TI  - N-succinimidyl ester of ofloxacin--a novel prodrug.

PMID- 7568319
TI  - Extractum Fagopyri reduces atherosclerosis in high-fat diet fed rabbits.
AB  - A group of 30 male mongrel rabbits was divided into 3 subgroups: controls,
      animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil,
      HFD + Extr. Fagopyri (EF) were treated for 12 weeks. Surface areas of lipid
      deposites after 12 weeks of treatment measured planimetrically in the intima of
      the aorta, averaged 86.5% in HFD-fed animals, but 68.6% in EF treated rabbits.
      The positive effect of EF was confirmed histopathologically. The finding of this
      study is that the EF administration results in the reduction of atherosclerotic
      plaque formation.

PMID- 7568322
TI  - Studies on pyrazine derivatives, XXIX: Synthesis of N1-thioamido substituted
      pyrazincarboxyamidrazones with expected tuberculostatic activity.

PMID- 7568321
TI  - Cytotoxic activity of some (E)-7-arylidene-2 H,6 H-naphtho-[1,8-bc]furan-2,6
      diones and correlation with their electronic parameters.

PMID- 7568324
TI  - [Enzyme immunoassay for determination of tiaprofenic acid (Surgam)].

PMID- 7568323
TI  - Preparation, local anaesthetic and antiarrhythmic activity of
      pyrrolidinomethylcyclohexyl esters of alkoxysubstituted phenylcarbamic acids.

PMID- 7568325
TI  - Anthocyanidines as inhibitors of xanthine oxidase.

PMID- 7568328
TI  - International Union of Pharmacology Committee on Receptor Nomenclature and Drug
      Classification. IX. Recommendations on terms and symbols in quantitative
      pharmacology.

PMID- 7568327
TI  - 100 years of ibogaine: neurochemical and pharmacological actions of a putative
      anti-addictive drug.

PMID- 7568329
TI  - International Union of Pharmacology. X. Recommendation for nomenclature of alpha
      1-adrenoceptors: consensus update.

PMID- 7568326
TI  - Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes.

PMID- 7568330
TI  - Enzymes and transport systems involved in the formation and disposition of
      glutathione S-conjugates. Role in bioactivation and detoxication mechanisms of
      xenobiotics.

PMID- 7568331
TI  - The search for synergy: a critical review from a response surface perspective.

PMID- 7568332
TI  - Cytochemical localization of the acetone-inducible cytochrome P-450 isoform,
      CYP2E1, in murine colonic epithelium.
AB  - Immunolocalization of a toxicologically important cytochrome P-450 isoform, the
      alcohol-inducible CYP2E1, was examined in mouse colon. Male CD-1 mice (30-40 g)
      were exposed to acetone (1% v/v), a potent inducer of hepatic CYP2E1, in drinking
      water for 14 days. Tissue sections were fixed in 1% paraformaldehyde and
      incubated with anti-rat CYP2E1 polyclonal antibody. Immunohistochemical staining
      on tissue sections was performed using the indirect peroxidase-antiperoxidase
      method. In acetone-exposed mice, immunoreactivity was localized exclusively
      within the cytoplasm of surface epithelial cells of the proximal colon.
      Infrequently, only very faint staining was evident in colons of untreated control
      mice. Using the same monospecific antibody, the presence of CYP2E1 was confirmed
      by Western blot analysis. A 2-to 3-fold elevation in immunoreactivity
      corresponding to cytochrome P-4502E1 was found in colon microsomes isolated from
      acetone-exposed form acetone-exposed mice. Further evidence for colonic CYP2E1 is
      provided by elevation (up to 2.5-fold) in levels of chlorzoxazone 6-hydroxylase,
      a CYP2E1 substrate, after acetone treatment. The significance of these finding is
      discussed in terms of the potential for proximal colonic epithelial cells to
      participate directly in bioactivation of dietary promutagenic substances.

PMID- 7568333
TI  - Cytochrome P450 inhibitors attenuate the hypotonic shock-induced increases in K+
      efflux in LLC-PK1 cells.
AB  - Cell volume regulation in LLC-PK1 cells was evaluated by measuring 86Rb efflux
      (rate constant), used as an indicator of K+ efflux. Hypotonic shock induced a
      transient increase in the rate constant which returned to baseline values after
      15 min. ETYA, an arachidonic acid-competitive antagonist as well as the
      cytochrome P450 inhibitors SKF 525-A, clotrimazole and 7-ethoxyresorufin,
      inhibited the hypotonic shock-induced increment in the rate constant. Arachidonic
      acid did not change hypotonic shock-induced increments in K+ efflux. LLC-PK1
      cells were unable to metabolize 14C-arachidonic acid. We concluded that although
      arachidonic acid inhibitors block the hypotonic shock-induced increment in K+
      efflux, this effect cannot be related to inhibition of arachidonic acid
      metabolism.

PMID- 7568334
TI  - MAO inhibitors, clorgyline and lazabemide, prevent hydroxyl radical generation
      caused by brain ischemia/reperfusion in mice.
AB  - The effects of clorgyline, the MAO-A inhibitor, and lazabemide, the MAO-B
      inhibitor, on the levels of the hydroxyl radicals appearing in the cerebral
      ventricles of mice during brain ischemia/reperfusion were examined by using a
      salicylate trapping method. The amount of hydroxyl radicals formed peaked at 20
      min after reperfusion (approximately 150% vs. basal level). The dopamine level
      markedly increased shortly after the initiation of an ischemic insult and
      thereafter waned. By contrast, the concentration of 3,4-dihydroxyphenylacetic
      acid (DOPAC) level decreased during a 40-min period of ischemia, gradually
      returning to the preischemic basal level upon reperfusion. The ischemia
      reperfusion-induced hydroxyl radical generation was attenuated by 3 mg/kg of
      clorgyline and lazabemide. Furthermore, mice pretreated with these MAO inhibitors
      showed decreased DOPAC levels in comparison with those of their respective
      vehicle-treated control groups; recovery of the reduced DOPAC level was also
      delayed. In conclusion, it is likely that both type A and type B MAOs participate
      in the generation of hydroxyl radicals during brain ischemia/reperfusion. This
      finding suggests the possible use of MAO inhibitors as neuroprotective agents for
      treating ischemic injury.

PMID- 7568335
TI  - Suppression of hypotensive responses of captopril and enalapril by the kallikrein
      inhibitor aprotinin in spontaneously hypertensive rats.
AB  - The present investigation evaluated the effects of aprotinin, an inhibitor of
      kallikrein, on blood pressure responses, heart rate, and duration of hypotension
      induced by acute administration of captopril and enalapril (angiotensin
      converting enzyme inhibitors) in anaesthetized spontaneously hypertensive rats.
      Captopril (20 mg/kg) and enalapril (20 mg/kg) administered intravenously caused a
      significant (p < 0.001) fall in systolic and diastolic blood pressures in the
      absence of aprotinin. In contrast, captopril (20 mg/kg) and enalapril (20 mg/kg)
      failed (p > 0.05) to cause a fall in systolic and diastolic blood pressures in
      the presence of aprotinin (2 mg/kg). Captopril and enalapril were able to
      significantly reduce the heart rate (p < 0.05 and p < 0.001) in the presence as
      well as in the absence of aprotinin. The duration of hypotension produced by
      captopril and enalapril was abolished significantly (p < 0.001) in the presence
      of aprotinin. These findings may suggest that captopril and enalapril caused
      hypotension via the kallikrein pathway, since the kallikrein inhibitor aprotinin
      can antagonize the hypotensive responses of these agents. Thus, kallikrein may be
      an independent mediator in the regulation of blood pressure.

PMID- 7568336
TI  - Characteristics of DQ2511-induced relaxation in isolated dog, monkey and human
      arteries.
AB  - DQ2511, a possible antiulcer agent, relaxed dog, monkey and human arterial strips
      from various organs; the effect was most evident in the gastroepiploic artery.
      The relaxation was not influenced by timolol, atropine, dopamine receptor
      antagonists, and K+-channel blockers, but partially attenuated by oxyhemoglobin
      endothelium denudation. Treatment with DQ2511 increased the relaxant response to
      sodium nitroprusside and a prostaglandin I2 analog in dog gastroepiploic arteries
      and potentiated the stimulating effect of these agonists on the contents of
      cyclic GMP and cyclic AMP, respectively. It is concluded that DQ2511 relaxes
      gastroepiploic arteries predominantly over the other arteries; the relaxation
      appears to be derived partially from phosphodiesterase inhibition.

PMID- 7568337
TI  - Vasodilator effects of liriodenine and norushinsunine, two aporphine alkaloids
      isolated from Annona cherimolia, in rat aorta.
AB  - The effect of two aporphines, liriodenine and norushinsunine, isolated from
      Annona cherimolia, were studied in the rat aorta in order to examine their
      mechanism of action. Both alkaloids (10(-7) - 10(-4) mol/l) showed relaxant
      effects on the contractions elicited by 10(-6) mol/l noradrenaline (NA) or 80
      mmol/1 KCl, but, while liriodenine showed a nonspecific relaxant action on both
      spasmogens, norushinsunine was more potent on KCl-induced contraction. In Ca2+
      free medium, both alkaloids (0.1 mmol/l) inhibited the responses elicited by NA,
      but not those elicited by caffeine. This inhibitory action occurred when the
      alkaloids were present during the release of the Ca2+ internal stores or during
      the refilling process. These results suggest that the two aporphines show a
      relaxant action in rat aorta which is mediated by an interaction with alpha1
      adrenoceptors and an alteration of the Ca2+ entry via voltage-operated channels.
      Norushinsunine exhibits a certain degree of selectivity as an L-type Ca2+ channel
      blocker.

PMID- 7568338
TI  - K-channel opening activity of ZD6169 and its analogs: effect on 86Rb efflux and
      3H-P1075 binding in bladder smooth muscle.
AB  - Zeneca ZD6169, (S)-N-(4-benzoylphenyl)-3,3,3-trifluoro- 2-hydroxy-2
      methylpropionamide, is a novel compound which relaxes urinary bladder smooth
      muscle in vitro. The effect of ZD6169 and two of its analogs on 86Rb efflux and
      3H-P1075 binding in guinea pig bladder strips was investigated to characterize
      the K-channel opening properties of this compound. ZD6169 concentration
      dependently increased the rate of 86Rb efflux from guinea pig bladder strips.
      86Rb efflux evoked by ZD6169 and its analogs was blocked by glibenclamide (30
      muM) but not by charybdotoxin, apamin or alpha-dendrotoxin, suggesting that this
      compound activates KATP channels in guinea pig bladder. In addition, interaction
      of ZD6169 with KATP channels was also confirmed in human bladder smooth muscle
      cells. Specific binding of 3H-P1075, a potent opener of KATP channels, to guinea
      pig urinary bladder strips was observed. 3H-P1075 binding was inhibited by known
      KATP openers. ZD6169 inhibited binding of 3H-P1075 to urinary bladder strips like
      other structurally different KATP openers, e.g. cromakalim and pinacidil.
      Potencies for inhibition of 3H-P1075 binding by ZD6169 and other potassium
      channel openers correlate well with potencies for increase in 86Rb efflux and
      bladder muscle relaxation studies. It is concluded that Zeneca ZD6169 is a
      potassium channel opener which activates ATP-sensitive K-channels in guinea pig
      urinary bladder strips as well as in human bladder cells. Furthermore, binding
      studies suggest that the effects of ZD6169 and its analogs are mediated by
      binding to the site labeled by 3H-P1075 in guinea pig bladder strips.

PMID- 7568339
TI  - Pharmacological regulation of transcription factor binding.
AB  - Organisms respond to extracellular stimuli by changing the expression of genes.
      Stimulation of the cell often induces a cascade of intracellular events that
      leads to activation of transcription factor DNA-binding complexes which modulate
      the transcription rate. Many cellular processes including development of the
      organism are dependent on these proteins to maintain proper levels of mRNA. A
      diversity of mechanisms has evolved to coordinate transcription factor binding to
      the specific DNA element which affects mRNA synthesis. Precise regulatory
      processes are present at the level of transcription, translation and
      posttranslation. Often, posttranslational processes alter affinities of factors
      to DNA-binding sites. In this review, the molecular controls of transcription
      factor binding to DNA will be examined, with specific examples of the
      pharmacologic regulation of transcription factor binding to DNA.

PMID- 7568340
TI  - Selective suppression of glutathione S-transferase activities in rat primary
      hepatocytes by growth hormone.
AB  - Glutathione S-transferases (GSTs) detoxify diverse electrophilic chemicals,
      including anticancer drugs. Containing at least 100 microM total GST, the adult
      rat liver has abundant alpha and mu class GST isoenzymes. We utilized primary
      cultured rat hepatocytes, maintained in chemically defined medium, to examine
      direct regulation of GST activities by human growth hormone (hGH). Maintenance of
      GST activities in this primary cultured hepatocyte system for 8 days allowed
      subsequent study of GST regulation by hGH. Protein concentration, cell number,
      DNA content, and viability did not significantly differ (p > 0.05) between the
      untreated and hGH (2 micrograms/ml)-treated hepatocytes. However, hGH treatment
      decreased mu GST activity (p < 0.05), whereas alpha GST activity was unaltered.
      As positive controls for our culture system and to corroborate our findings, we
      examined phenobarbital induction of GST activities and hGH regulation of certain
      cytochrome P450-dependent testosterone hydroxylases.

PMID- 7568341
TI  - Biliary cefpiramide excretion: its relation to biliary excretion of bile acids
      and sulfobromophthalein.
AB  - Cefpiramide, a beta-lactam antibiotic, has been reported to be excreted from
      hepatocytes into the bile by a carrier-mediated system. Herein, the relationship
      of biliary cefpiramide excretion to the excretion of bile acids and
      sulfobromophthalein was studied in rats. Biliary cefpiramide excretion was
      markedly inhibited by sulfobromophthalein, lithocholate-3-O-glucuronide and
      taurolithocholate-3-sulfate, whereas it was not inhibited by ursodeoxycholate or
      taurocholate. However, the inhibitory effect of cefpiramide on the biliary
      excretion of sulfobromophthalein or lithocholate-3-sulfate was very small. These
      findings indicate that, although cefpiramide is excreted by a process common to
      organic anions and bile acid sulfate and glucuronide, two or more excretory
      pathways for organic anions exist and cefpiramide has affinity for only one of
      these carriers.

PMID- 7568343
TI  - Effects of the biguanide metformin on splanchnic blood flow in rats: preferential
      and dose-dependent increase in islet blood flow.
AB  - The aim of the present study was to evaluate if metformin, a biguanide used in
      the treatment of noninsulin-dependent diabetes, induced any changes in splanchnic
      circulation. For this purpose, anesthetized rats were injected intraperitoneally
      with saline alone (1 ml/kg BW) or metformin (15 or 30 mg/kg BW) 30 min before
      blood flow measurements. No effects on blood glucose or serum insulin
      concentrations could be discerned after administration of metformin. Both
      duodenal, whole pancreatic and islet blood flow were approximately doubled by the
      lowest dose (15 mg/kg BW) metformin. However, the higher dose (30 mg/kg BW) did
      not affect duodenal or pancreatic blood flow, whereas islet blood flow was
      markedly increased also in this group of animals. It is concluded that the blood
      flow to the pancreatic islets can be specifically enhanced by metformin. To what
      extent this contributes to the antihyperglycemic action of the drug is presently
      unknown.

PMID- 7568342
TI  - Zeneca ZD6169 and its analogs from a novel series of anilide tertiary carbinols:
      in vitro KATP channel opening activity in bladder detrusor.
AB  - The potassium (K+) channel opening activity of Zeneca ZD6169 and one of its
      pyridylsulfonyl analogs from the anilide tertiary carbinol series was
      ascertained. Their mechanoinhibitory effects on the myogenic activity of the
      guinea pig bladder detrusor muscle were measured in a set of functional assays.
      Elevating the K+ concentration in the tissue bath from 15 to 80 mmol/l increased
      the IC50 value of ZD6169 from 1.61 +/- 0.22 223 +/- 37 mumol/l. This result
      suggests that ZD6169 may act as a K+ channel opener. Similar to the prototypic
      ATP-sensitive K+ (KATP) channel opener cromakalim, the K+ channel openers from
      the anilide tertiary carbinol series displayed stereoselective mechanoinhibitory
      activity only in the test protocol in which the detrusor was stimulated with 15
      mmol/l KCl. Being the active enantiomer, ZD6169 has an activity more than 30-fold
      higher than the less active enantiomer. ZD6169 at 10 mumol/l hyperpolarized the
      guinea pig detrusor membrane potential by 6.1 +/- 1.2 mV and increased the whole
      cell KATP current in isolated guinea pig smooth muscle cells by 34.9 +/- 7.9 pA.
      This is comparable to the increase of 26.8 +/- 5.0 pA obtained with 10 mumol/l of
      lemakalim, the active enantiomer of cromakalim. The K+ channel opening activity
      of ZD6169 and the pyridylsulfonyl analog was competitively antagonized by the
      KATP channel blocker glibenclamide in the guinea pig detrusor with a pA2 value of
      7.2. This activity, however, was unaffected by blockers of small and large
      conductance Ca-dependent K+ channels, such as apamin and charybdotoxin,
      respectively. The present study showed that Zeneca ZD6169 and its analog from the
      anilide tertiary carbinol series are K+ channel openers that activate KATP
      channels in vitro to relax bladder detrusors.

PMID- 7568344
TI  - Acute effects of indometacin on cerebral blood flow in man.
AB  - Blood velocity changes in the internal carotid artery were estimated using
      Doppler ultrasound before, during and after injection of indometacin or placebo
      in 7 healthy adults. Upon injection of the active substance there was a rapid
      reduction in blood velocities in the internal carotid artery, increasing with
      increasing doses of indometacin. A fall in end-expiratory PCO2 was also observed,
      indicating a state of hyperventilation. The observed relative reduction in
      cerebral blood flow was much higher in all subjects than the expected reduction
      due to the accompanying drop in PCO2. Experiments in which arterial PCO2 was kept
      constant showed that indometacin also causes a reduction in blood velocity
      independent of changes in PCO2. We suggest that indometacin has both a direct
      effect on the cerebral microcirculation, and an additional effect mediated
      through induction of hyperventilation. The drug probably affects the respiratory
      center through an increase in intracerebral PCO2 due to reduced perfusion.

PMID- 7568345
TI  - Comparison of the hallucinogenic indole alkaloids ibogaine and harmaline for
      potential immunomodulatory activity.
AB  - The immunomodulatory potential of the indole alkaloids ibogaine and harmaline was
      examined in a panel of in vitro immune function assays. These assays were chosen
      to assess T-cell regulatory and effector function, B-cell function, macrophage
      function, and natural killer-cell function. The in vitro exposure to either
      ibogaine or harmaline resulted in a dose-related suppression of all immune
      functions examined except macrophage function. This suppression was noted at
      various concentrations in different assays, but was generally only associated
      with high concentrations (10-100 mumol/l).

PMID- 7568346
TI  - Effects of ethanol on peripheral benzodiazepine binding sites in the mouse
      cerebellum and brain stem.
AB  - [3H]PK 11195 binding to the peripheral benzodiazepine binding site was
      investigated in the brain and liver of mice treated with ethanol (4 g/kg, p.o.)
      daily for 5 days. In the brain stem, Bmax was decreased by 78% in the ethanol
      treated group with unaltered Kd (2 nM). The ethanol-withdrawn group did not
      differ from the control group in both parameters. In the cerebellum, Bmax was
      decreased by 74% but the binding affinity increased 5-fold as the Kd decreased
      from 10 to 2 nM. The ethanol-withdrawn group did not differ significantly from
      the ethanol-treated group. No changes were observed in the cerebrum and liver.
      These results further support the idea that [3H]PK 11195 binding may be a useful
      marker for ethanol consumption. The observed changes in these binding sites may
      represent a functional adaptive response to the ethanol insult and/or a role in
      the mediation of the effects of ethanol.

PMID- 7568347
TI  - President Cleveland's secret operation: the effect of the office upon the care of
      the president.

PMID- 7568349
TI  - Must an internship be miserable?

PMID- 7568348
TI  - A medicine intern's bestiary.

PMID- 7568350
TI  - Prudence: the guide for perplexed physicians in the third millennium.

PMID- 7568351
TI  - Read Don Quixote.

PMID- 7568352
TI  - A patient in the teaching hospital: balancing privacy and education.

PMID- 7568353
TI  - Sherlock Holmes and his gasogene.

PMID- 7568354
TI  - Choosing medicine: motive, incentive, obligation.

PMID- 7568355
TI  - Teaching clinical medicine in an era of change.

PMID- 7568356
TI  - Will, lotus-eaters, and a thousand paper cranes.

PMID- 7568357
TI  - Bethesda.

PMID- 7568358
TI  - Lessons for corporate medical directors.

PMID- 7568359
TI  - William James and vivisection.

PMID- 7568360
TI  - Dual degree physicians.

PMID- 7568361
TI  - Dual degree physicians.

PMID- 7568362
TI  - Traditional medicine in Africa.

PMID- 7568363
TI  - Nasal anthrax in Boston.

PMID- 7568364
TI  - Race and culture in medical education.

PMID- 7568365
TI  - Time for men and women of medicine to speak out.

PMID- 7568366
TI  - Retirement: are you ready?

PMID- 7568367
TI  - Effects of fluoxetine on aggressive behavior of adult inpatients with mental
      retardation and epilepsy.
AB  - Nineteen mentally retarded inpatients with epilepsy and a history of current or
      recent aggressive behavior were treated with 20 mg of fluoxetine daily. All were
      concurrently taking other psychotropic medications, including carbamazepine and
      neuroleptics. A standardized rating scale (MOAS) was used to assess the effects
      of fluoxetine on aggressive behavior. There were wide individual differences in
      drug response. In nine patients, fluoxetine treatment was associated with
      increased aggression, while drug withdrawal led to a decrease to below
      pretreatment levels. Two hypotheses concerning the apparent association between
      fluoxetine and increased aggression are discussed: 1) adverse effects secondary
      to either drug interaction or fluoxetine overmedication; and 2) a specific
      serotonergically mediated effect on the regulation of aggression. This study
      suggests that the clinician who treats mentally retarded patients with impulsive
      aggressive behavior should remain aware that fluoxetine may have diverse effects
      on aggression that vary over time and interindividually.

PMID- 7568368
TI  - Red-cell and serum folate levels in depressed inpatients who commit violent
      suicide: a comparison with control groups.
AB  - There has been some discussion in the recent literature regarding the possible
      relationship between peripheral levels of folate and serotonin deficiency in the
      CNS. At the same time, such a serotonin deficiency has been implicated in the
      biology of suicidal behavior. Thus, decreased peripheral folate levels may be
      expected in patients who commit violent suicide. In this study, the red-cell and
      serum folate levels in nine persons who later committed suicide are compared with
      those in age- and sex-matched control groups. A one-way analysis of variance
      showed no significant difference between the groups.

PMID- 7568369
TI  - Growth-hormone response to clonidine in panic disorder patients in comparison to
      patients with major depression and healthy controls.
AB  - Growth-hormone (GH) responses to the alpha 2-adrenoceptor agonist clonidine were
      measured in 9 panic disorder patients, in 9 patients fulfilling DSM-III-R
      criteria for major depressive episode, and in 9 age- and sex-matched controls. GH
      responses to clonidine were not significantly different between the groups. The
      data do not agree with the assumption that blunted GH responses to clonidine
      represent a general feature of panic disorder or major depression.

PMID- 7568370
TI  - Different patterns of sexual dysfunctions associated with psychiatric disorders
      and psychopharmacological treatment. Results of an investigation by
      semistructured interview of schizophrenic and neurotic patients and methadone
      substituted opiate addicts.
AB  - Little is known about sexual dysfunctions associated with psychiatric disorders
      and psychopharmacological treatment. In the present study schizophrenic patients
      (n = 45, mostly under neuroleptic treatment), neurotic patients (n = 50, mostly
      treated without medication), methadone-substituted opiate addicts (n = 37), and
      normal controls (n = 41) were included. They were interviewed with the aid of a
      sex-differentiated semistructured questionnaire on sexual function. All the
      methadone-substituted opiate addicts and nearly all the schizophrenic patients
      suffered from dysfunctions in at least one criterion. The three clinical groups
      differed significantly from the controls in sexual interest, emotional arousal,
      physiological arousal (erectile function/vaginal lubrication), performance
      (ejaculatory function/vaginism, dyspareunia), and orgasm satisfaction.
      Characteristic patterns of dysfunction were found in the male patients. The
      schizophrenic patients had significantly more dysfunctions of interest,
      physiological arousal, performance, and orgasm than the controls. Emotional
      arousal, erectile and ejaculatory functions, and orgasm satisfaction were
      impaired more frequently in the male schizophrenics than in the neurotic
      patients. Reduced sexual interest, emotional arousal, and orgasm satisfaction
      were reported more frequently by the methadone-substituted opiate addicts than by
      the neurotic men. Emotional arousal was even more frequently reduced than in the
      schizophrenic men. There was no correlation between sexual dysfunction and
      particular neuroleptics or neuroleptic or methadone dosage. The results are
      compared with the literature and suggestions made for further investigations.

PMID- 7568371
TI  - Notes on the use of fluvoxamine as treatment of depression in HIV-1-infected
      subjects.
AB  - Fluvoxamine belongs to the class of selective serotonin reuptake inhibitors
      (SSRIs) which have recently gained large popularity as antidepressant agents
      essentially because they lack the most troublesome adverse effects of older
      antidepressants (i.e. tricyclic antidepressants) such as anticholinergic effects
      and cardiotoxicity. Recent studies in the literature suggest that HIV-1 infected
      subjects are affected by depressive episodes with a relatively high frequency,
      often requiring an antidepressant treatment. Due to its favorable adverse effects
      profile, we used fluvoxamine as first line treatment for sixteen depressed HIV-1
      infected subjects. They were administered the drug at a daily dosage of 100 mg in
      the evening. Fluvoxamine provided a good clinical efficacy for six of these
      patients, whereas the other ten had to discontinue the drug because of the
      presence of severe adverse effects such as acute total insomnia, gastro
      intestinal disturbances together with anorexia, aggressive and impulsive behavior
      and excessive sedation. The observed fluvoxamine side-effects are not typical or
      specific for this particular patient group since they are also described in
      seronegative subjects taking fluvoxamine; however, our findings seem to indicate
      that they become more frequent and more severe when the drug is administered to
      HIV-1 infected patients.

PMID- 7568372
TI  - A seizure, and electroencephalographic signs of a lowered seizure threshold,
      associated with fluvoxamine treatment of obsessive-compulsive disorder.
AB  - A 38-year-old patient with severe obsessive-compulsive disorder received
      fluvoxamine in a clinical study. Psychometric ratings showed marked clinical
      improvement in the third week of fluvoxamine administration, but after 8 weeks,
      at a dose of 300 mg per day, he suffered a grand mal seizure after drinking a
      glass of beer (0.2 liter). He had no history of previous epileptic seizures.
      Careful neurological evaluation including computer tomography and magnetic
      resonance imaging of the brain revealed no signs of acute disease. EEG before the
      fit did not show epileptiform activity; after the fit, spikes and spike-wave
      complexes appeared, which disappeared upon discontinuation of fluvoxamine. Since
      his obsessive-compulsive symptoms had responded well to fluvoxamine and worsened
      after its discontinuation, the drug was cautiously reintroduced. Improvement of
      the obsessive-compulsive symptoms was observed again, but spikes and spike-wave
      complexes reappeared at a dose of 50 mg per day. Under anticonvulsant treatment
      with carbamazepine, fluvoxamine was increased to 100 mg per day. No seizures
      occurred during a follow-up to two years.

PMID- 7568373
TI  - Tranylcypromine in narcolepsy.
AB  - The narcolepsy syndrome consists of excessive daytime somnolence, cataplexy,
      hallucinations, and sleep paralysis. Data on the effects of tranylcypromine are
      scant. We report on a patient with severe narcolepsy in whom administration of
      tranylcypromine led to freedom from hallucinations, nightmares, sleep paralysis,
      and rapid eye movements (REM), with considerable amelioration of cataplexy and
      increased daytime alertness. Muscle atonia and low-voltage desynchronized
      cortical activity during REM sleep did not change. Tranylcypromine warrants
      further study in narcolepsy.

PMID- 7568375
TI  - Ionization chamber dosimetry of proton beams using cylindrical and plane parallel
      chambers. Nw versus Nk ion chamber calibrations.
AB  - Determinations of the absorbed dose in a 170 MeV proton beam have been performed
      using seven ionization chambers of different types: five cylindrical (two FWT IC
      18 and three NE-2571, of which one was modified to have the central electrode
      made of graphite) and two plane parallel (NACP-02 and Roos FK-6). The ionization
      was converted into absorbed dose in the proton beam according to the
      generalization of the formalism provided by the IAEA Code of Practice (TRS 277),
      which enables the use of the same equations for all kinds of beam used in
      radiotherapy. The absorbed dose obtained with the two IC-18 chambers, a chamber
      type commonly used as a reference in proton beams, was up to 1.5% lower than that
      obtained with the Farmer NE-2571 chamber, which was used as the reference in this
      work when calibration factors in terms of NK were used. To investigate this
      difference, experimental ND factors for six chambers (the two IC-18 chambers, the
      NACP-02, the FK-6 and two of the NE-2571 chambers) were determined in a high
      energy electron beam. The procedure commonly recommended for plane parallel ion
      chambers was used for all the chambers, using the same reference chamber, a
      Farmer NE-2571. In the 170 MeV proton beam all the ND factors yielded consistent
      absorbed dose determinations within the estimated experimental uncertainties.
      This finding calls into question the value of the product kattkm for the IC-18
      chamber given by the IAEA Code of Practice used in this comparison, and points at
      possible chamber to chamber variations that theoretical kattkm factors cannot
      predict. The investigations enabled the determination of the Pwall(60Co) factor
      of the Roos FK-6 plane parallel chamber, yielding 1.003 +/- 0.5%, and a
      correction for the effect of the aluminium central electrode of NE-2571 chambers
      in proton beams, equal to 1.003 +/- 0.4%. Two of the chambers (the plane parallel
      FK-6 and the modified cylindrical NE-2571) were provided with calibration factors
      in terms of absorbed dose to water, Nw, at the quality of 60Co by the Primary
      Standard Dosimetry Laboratory in Germany (PTB). Using the Nw formalism excellent
      agreement was found with the determination based on the experimental ND, giving
      support to the implementation of the NW procedure in therapeutic proton beams.

PMID- 7568376
TI  - Experimental determination of the beam quality dependence factors, kQ, for
      ionization chambers used in photon and electron dosimetry.
AB  - Dosimetry in radiotherapy with ionization chambers calibrated in 60Co gamma beams
      in terms of absorbed dose to water, DW, can be performed if a factor
      conventionally denoted as kQ is known. The factor kQ depends on the beam quality
      and the chamber characteristics. Calculated values of the kQ factors for many
      types of ionization chamber have been recently published. In this work the
      experimental determination of the kQ factors for various ionization chambers was
      performed for 6 MV and 15 MV photon beams and for a 14 MeV electron beam. The kQ
      factors were determined by a procedure based on relative measurements performed
      with the ionization chamber and ferrous sulphate solution in 60Co gamma radiation
      and accelerator beams, respectively. The experimental kQ values are compared with
      the calculated values so far published. Theoretical and experimental kQ values
      are in fairly good agreement. The uncertainty in the experimental kQ factors
      determined in this work is less than about 1%, that is, appreciably smaller than
      the uncertainty of about 1.5% reported for the calculated values.

PMID- 7568377
TI  - A European quality assurance network for radiotherapy: dose measurement
      procedure.
AB  - In the frame of the experimental implementation of a European quality assurance
      network for external radiotherapy, the methodology in the European Measuring
      Centre (MC) is presented. Mailed TL dosimeters are used for the check of the beam
      output and of the beam quality of photon beams. The thermoluminescent material is
      PTL 717 LiF powder. The readings were first performed on a manual, and then on an
      automatic reader, with standard deviations of the mean of 0.7% for one dosimeter.
      Corrections for supralinearity and for the energy dependence of the dosimeter
      response are applied. An original method has been developed to correct for the
      variation of the LiF response as a function of time. It is shown that the
      sensitivity of the powder changes during storage, leading to a kind of 'inverse
      fading'. The global uncertainty of the TL postal measurement procedure is
      estimated to be about 1.5% for the 60Co beams and 2% for the x-ray beams.
      Intercomparisons with the IAEA and with the EORTC have shown an agreement better
      than 2% for all energies. It can be concluded that the results of the MC are
      suitable for the requirements of a European quality assurance network.

PMID- 7568374
TI  - An improved energy-range relationship for high-energy electron beams based on
      multiple accurate experimental and Monte Carlo data sets.
AB  - A theoretically based analytical energy-range relationship has been developed and
      calibrated against well established experimental and Monte Carlo calculated
      energy-range data. Only published experimental data with a clear statement of
      accuracy and method of evaluation have been used. Besides published experimental
      range data for different uniform media, new accurate experimental data on the
      practical range of high-energy electron beams in water for the energy range 10-50
      MeV from accurately calibrated racetrack microtrons have been used. Largely due
      to the simultaneous pooling of accurate experimental and Monte Carlo data for
      different materials, the fit has resulted in an increased accuracy of the
      resultant energy-range relationship, particularly at high energies. Up to date
      Monte Carlo data from the latest versions of the codes ITS3 and EGS4 for
      absorbers of atomic numbers between four and 92 (Be, C, H2O, PMMA, Al, Cu, Ag, Pb
      and U) and incident electron energies between 1 and 100 MeV have been used as a
      complement where experimental data are sparse or missing. The standard deviation
      of the experimental data relative to the new relation is slightly larger than
      that of the Monte Carlo data. This is partly due to the fact that theoretically
      based stopping and scattering cross-sections are used both to account for the
      material dependence of the analytical energy-range formula and to calculate
      ranges with the Monte Carlo programs. For water the deviation from the
      traditional energy-range relation of ICRU Report 35 is only 0.5% at 20 MeV but as
      high as -2.2% at 50 MeV. An improved method for divergence and ionization
      correction in high-energy electron beams has also been developed to enable use of
      a wider range of experimental results.

PMID- 7568378
TI  - The physical performance of different x-ray contrast agents: calculations using a
      Monte Carlo model of the imaging chain.
AB  - A Monte Carlo computational model of the imaging chain has been used to
      investigate the performance of x-ray contrast agents with atomic number, Z, 53 <
      or = Z < or = 90 with respect to physical image quality descriptors (contrast and
      signal to noise ratio, SNR) and patient mean absorbed dose. Contrast agents of
      equal molar concentrations were used within a water slab (simulating the
      patient). The imaging conditions were chosen to represent adult and paediatric
      examinations. For all tube potentials studied (40-140 kV), the contrast agents
      with the highest atomic numbers (bismuth and thorium) gave the highest contrast.
      In analogue screen-film imaging, several other contrast agents could produce a
      higher image contrast than iodine in a limited range of tube potentials. This
      advantage could alternatively be effected as a reduced amount of administered
      contrast agent, or as a reduced mean absorbed dose in the patient. In digital
      imaging, a lower mean absorbed dose for a constant SNR than that with iodine can
      be achieved for ranges of tube potentials and contrast agents. Bismuth and
      thorium yield a lower dose than iodine at all studied tube potentials. Gadolinium
      and erbium could alternatively be used at a broad range of tube potentials above
      90 kV with a dose penalty of only 5-20%.

PMID- 7568379
TI  - Transmission maximum-likelihood reconstruction with ordered subsets for cone beam
      CT.
AB  - An iterative algorithm is presented for accelerated reconstruction of cone beam
      transmission CT data (CBCT). CBCT supplies an attenuation map for SPECT
      attenuation compensation and anatomical correlation. Iterative algorithms are
      necessary to reduce truncation artifacts and 3D reconstruction artifacts. An
      existing transmission maximum-likelihood algorithm (TRML) is accurate but the
      reconstruction time is too long. The new algorithm is a modified EM algorithm,
      based on ordered subsets (OSEM). OSEM was evaluated in comparison to TRML using a
      thorax phantom and a 3D Defrise phantom. A wide range of image measures were
      evaluated, including spatial resolution, noise, log likelihood, region
      quantification, truncation artifact removal, and 3D artifact removal. For
      appropriate subset size, OSEM produced essentially the same image as TRML, but
      required only one-tenth as many iterations. Thus, adequate images were available
      in two to four iterations (20-30 min on a SPARC 2 workstation). Further, OSEM
      still approximately maximizes likelihood: divergence occurs only for very high
      (and clinically irrelevant) iterations. Ordered subsets are likely to be useful
      in other geometries (fan and parallel) and for emission CT as well. Therefore,
      with ordered subsets, high-quality iterative reconstruction is now available in
      clinically practical reconstructions times.

PMID- 7568380
TI  - The assessment of the non-equilibrium effect in the 'Patlak analysis' of Fdopa
      PET studies.
AB  - 'Patlak analysis' is a common approach used in Fdopa PET studies to calculate the
      uptake constant (Ki) of the tracer. It is assumed in the Patlak analysis that the
      reversible compartment of tissue radioactivity used is in effective equilibrium
      with the tracer in plasma. Therefore, using the data prior to equilibrium is in
      conflict with the assumption, and its effect on the estimate thus needs to be
      examined. In this study, we used simulations to investigate the errors due to the
      violation of the equilibrium assumption. Two factors affecting the estimate of Ki
      were examined--the eigenvalue of the model response function and the shape of the
      input function. The Ki estimate obtained from the Patlak analysis was found to be
      markedly biased because the system is not in equilibrium during the first 2 h
      post Fdopa injection. The magnitude of the bias was found to be dependent on the
      time interval used in the analysis (10% difference when comparing results from
      intervals 30-120 min and 60-120 min) and on the eigenvalue of the response
      function (10% change in Ki when the eigenvalue was changed by 20% around the
      nominal value). The estimates are also affected by the intersubject variations in
      the plasma time-activity curves. Therefore, Patlak analysis users should
      interpret their results with caution, particularly when examining small
      intersubject differences and small changes due to physiological or
      pharmacological interventions.

PMID- 7568381
TI  - Single-photon transmission measurements in positron tomography using 137Cs.
AB  - Transmission measurements are an essential step in the quantification of
      radioisotope distributions in vivo using positron tomographic techniques. The
      development of a new technique for measuring transmission data that relies on the
      detection of photons in 'singles' mode rather than 'coincidence' mode no longer
      restricts the choice of transmission sources to those that decay by positron
      emission. The motivation for using the 'singles' mode of operation is the
      substantial increase in count rate that can be achieved. This corresponds to a
      great increase in the statistical accuracy of the transmission data. We propose
      137Cs as a suitable isotope for this purpose. 137Cs is more economical than 68Ge,
      the traditional source used for transmission measurements, in terms of longer
      half-life and lower financial cost. 137Cs can be used for transmission
      measurements without any recalibration of the tomograph, and the estimated
      spatial resolution is comparable to that obtained using annihilation photons. A
      simple extrapolation method is developed, which allows extrapolation of the
      attenuation coefficients measured at 662 keV to 511 keV. A dual-energy-window
      technique, whereby correction can be made on-the-fly during acquisition, is used
      for scatter correction. The measured linear attenuation coefficients agree with
      predicted values.

PMID- 7568382
TI  - The influence of glucose concentration upon the transport of light in tissue
      simulating phantoms.
AB  - The effect of glucose upon the transport of light in tissue-simulating phantoms
      is shown and its possible application for non-invasive glucose monitoring in
      diabetic patients is discussed. The aim of this paper is to investigate the
      physical background of this effect. The presence of glucose in an aqueous
      solution increases its refractive index and therefore has an influence upon the
      scattering properties of particles suspended in solution. Experimental data on
      the effect of glucose upon the scattering coefficient and the phase function of
      aqueous suspensions of spherical polystyrene particles are presented for near
      infrared wavelengths and compared to values predicted by Mie theory. The
      subsequent effect upon light transport in multiple scattering, tissue-simulating
      phantoms is demonstrated experimentally in a slab geometry and theoretically by
      applying diffusion theory. It is furthermore shown that optional measurements in
      the frequency domain allow changes of absorption and scattering coefficient to be
      separately determined. The possible magnitude of this glucose effect in tissue in
      vivo is discussed.

PMID- 7568383
TI  - The evaluation of nylon and polyethylene as build-up material in a neutron
      therapy beam.
AB  - In high-energy neutron beams a substantial amount of build-up material is
      required to irradiate biological samples under conditions of charged particle
      equilibrium. Ideally A-150 tissue-equivalent plastic is used for this purpose.
      This material is however not always readily available and hence the need for a
      substitute compound. The selected hydrocarbon should satisfy two requirements:
      the quality of the radiation on the distal side needs to be the same as that
      measured for A-150 plastic and the absorbed dose should remain consistent. A
      tissue-equivalent proportional counter operating at reduced pressure not only
      measures the absorbed dose accurately but provides a means for assessing the
      nature of a radiation field in terms of a secondary charged particle spectrum.
      Using build-up caps manufactured from nylon (type 6) and polyethylene, it is
      shown that the former is an acceptable substitute for A-150 plastic. The data
      further demonstrate that both the absorbed dose and the spectral character of the
      measured single-event distribution are altered when polyethylene is used and that
      these discrepancies are attributable to the higher hydrogen content of
      polyethylene.

PMID- 7568385
TI  - Is the clinical concept of spinal stiffness multidimensional?
AB  - BACKGROUND AND PURPOSE: This study investigated whether the poor reliability of
      judgments of posteroanterior (PA) spinal stiffness is due to rater bias or is a
      consequence of raters each having individual concepts of PA stiffness. SUBJECTS:
      Three pairs of manipulative physical therapists with a minimum of 5 years of
      experience took part in the study. METHODS: The raters were required to make
      stiffness judgments of a series of metal springs, and their performance at this
      task was compared with that obtained when they rated the PA stiffness of patients
      with low back pain. A range of reliability indices were calculated and evaluated
      to establish whether rater bias contributed to poor reliability in either task.
      The relationship between each rater's estimates of the magnitude of the stimuli
      and the measured stiffness of the springs was also assessed using the Pearson
      Product-Moment Correlation Coefficient. RESULTS: The average intraclass
      correlation coefficient (2, 1) for rating spring stiffness was found to be .60,
      whereas for human spines it was found to be .19. There was no evidence of rater
      bias contributing to poor reliability for rating stiffness of human spines. The
      average correlation between the rater's estimates of the magnitude of the stimuli
      and the measured stiffness of the stimuli was .80. CONCLUSION AND DISCUSSION:
      Physical therapists demonstrated much better ability to judge spring stiffness
      than the PA stiffness of human spines. This difference in performance implies
      that mechanical stiffness is not equivalent to the clinical concept of PA
      stiffness. Posteroanterior stiffness may have more than one dimension, and
      individual interpretation of stiffness as a construct may lead to rater
      disagreement in the clinic. The reliability of judgments of PA spinal stiffness
      may be enhanced in the future if its dimensions can be identified, defined, and
      taken into account during clinical procedures.

PMID- 7568384
TI  - Quantification of signal selection efficiency, extra volume suppression and
      contamination for ISIS, STEAM and PRESS localized 1H NMR spectroscopy using an
      EEC localization test object.
AB  - The three most widely used single-volume NMR localization techniques (ISIS, STEAM
      and PRESS) are assessed quantitatively for 1H spectroscopy using an EEC
      localization test object. Signal selection efficiency, suppression of outer
      volume signals and contamination are measured on a 1.5 T whole-body Siemens GBS1
      system. The ISIS signal selection efficiency (volume of interest (VOI), 1-125
      cm3) ranged from 90% to 95%, with T1 relaxation during the sequence shown to
      account for the observed 5-10% signal loss. Contamination for ISIS was found to
      be higher for smaller VOIS and ranged from approximately 45% (VOI = 1 cm3) to
      approximately 9% (VOI = 125 cm3). For PRESS, contamination ranged from 7% to 12%
      and it was between 3% and 8% for STEAM. However, the maximum signal selection
      efficiency for the latter two techniques (echo time, 270 ms) was relatively low
      (10-17%), and limited by T2 losses and the non-rectangular slice profiles of sinc
      pulses.

PMID- 7568386
TI  - Efficacy of comprehensive rehabilitation programs and back school for patients
      with low back pain: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: The use of back school as a treatment for low back pain
      is widespread, but determining the efficacy of this approach is complicated by
      variations in back schools and study methods across clinical trials. The purpose
      of this study was to conduct a meta-analysis to synthesize existing evidence on
      the efficacy of back school as either a primary intervention or a part of a
      comprehensive rehabilitation program for patients with low back pain. METHODS:
      The results of 19 prospective randomized controlled trials were evaluated.
      Quantitative reviewing procedures were used to calculate the effect sizes that
      compared patients receiving back school with those in a control or comparison
      group. Effect sizes were computed for 206 hypothesis tests involving 2,373
      patients. RESULTS: The average effect size for comprehensive rehabilitation
      programs that included back school (d = 0.28) was larger than the average effect
      size for programs that offered back school as the primary intervention (d = 
      0.14). When effect sizes were stratified by program type and outcome, the
      comprehensive programs were superior to primary back school programs with respect
      to pain reduction, increased spinal mobility, and increased strength. Both types
      of programs showed reasonable success with education/compliance outcomes (d =
      0.27-0.28). Lower effect sizes were found among the types of programs for
      disability and work/vocational outcomes (d < or = 0.20). CONCLUSIONS AND
      DISCUSSION: Back schools were most efficacious when coupled with a comprehensive
      rehabilitation program. Efficacy was supported for the treatment of pain and
      physical impairments and for education/compliance outcomes. Work/vocational and
      disability outcomes, however, were not improved substantially beyond control
      levels in comprehensive or primary back school programs. [Di Fabio RP. Efficacy
      of comprehensive rehabilitation programs and back school for patients with low
      back pain: a meta-analysis.

PMID- 7568387
TI  - Physical therapy management of the subluxated wrist in children with arthritis.
AB  - Arthritis commonly affects the hand and wrist in children and may contribute to
      loss of range of motion and force of the muscles surrounding the involved joints.
      The purpose of this case report is to describe a physical therapy protocol for
      managing a subluxated wrist in children with arthritis. Measures of range of
      motion and force of the wrist observed in two patients up to 2 years after the
      implementation of this protocol are also reported. The initial phase of the
      physical therapy program focused on realigning the subluxated wrist. Heat was
      used to manage flexor muscle tightness and increase tissue extensibility. The
      carpal bones were then realigned manually and supported in position with a cast
      for a period of 72 hours. Once alignment of the wrist was achieved, the emphasis
      of physical therapy was placed on increasing range of motion and force at the
      wrist joint through visits to the physical therapist and an extensive home
      program. Measurements of passive range of motion and active range of motion using
      a goniometer, grip forces using a modified sphygmomanometer, and peak torque of
      the wrist extensors using a dynamometer (measured in one patient) were recorded
      before and up to 2 years following the implementation of the protocol. There was
      an increase in wrist extension passive range of motion (35 degrees in both
      patients) and active range of motion (15 degrees in patient 1 and 25 degrees in
      patient 2) between the measurements obtained before and 1 to 2 years following
      the implementation of the protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568388
TI  - Low-load, prolonged stretch in the treatment of knee flexion contractures in
      nursing home residents.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to do a pilot test of the
      effectiveness of prolonged stretch (use of splint) in reducing knee flexion
      contractures more than a traditional program of passive range of motion (PROM) in
      a group of nursing home residents. SUBJECTS: The subjects were 28 nursing home
      residents with 10 degrees or more of knee flexion contracture bilaterally.
      Eighteen subjects completed the study. METHODS: Data were collected prior to the
      initiation of the intervention and at monthly intervals during the 6 months of
      treatment. Repeated measurements were made of hip, knee, and ankle range of
      motion (ROM); the torque required to maintain passive impairment. knee extension;
      knee pain; several indicators of function; and cognitive impairment. Both legs of
      each subject received PROM and manual stretching twice a week; in addition, one
      leg was given a prolonged stretch (use of a splint) five times a week. RESULTS:
      There were no differences in knee ROM between the side that received prolonged
      stretching and the side that received only PROM and manual stretching at the
      beginning of the study. No differences in ROM or torque measurements existed
      between the side that received prolonged stretching and the side that received
      only PROM and manual stretching at any interval, nor in ROM or torque over time
      for either side. Because of the low statistical power of the study, the results
      should be viewed with caution. CONCLUSION AND DISCUSSION: Physical therapists
      need to question whether prolonged stretch for nursing home residents with knee
      flexion contractures greater than 10 degrees is of any greater benefit than PROM
      and manual stretching. Investigations of other treatment protocols and treatment
      doses are needed, including work in the area of prevention of knee flexion
      contractures. For the pilot group of nursing home residents studied, gains in
      knee extension did not occur with the use of prolonged stretch for 3 hours a day,
      5 days per week. [Steffen TM, Mollinger LA. Low-load, prolonged stretch in the
      treatment of knee flexion contractures in nursing home residents.

PMID- 7568389
TI  - Influence of examiner experience and gender on interrater reliability of KT-1000
      arthrometer measurements.
AB  - BACKGROUND AND PURPOSE: Measurements of the integrity of knee ligaments are used
      to diagnose injuries as well as to document the state of recovery. Many factors,
      such as gender and experience of the examiner, are capable of influencing the
      reliability of such measurements. The purpose of this study was to determine the
      effects on interrater reliability of measurements obtained using the KT-1000
      arthrometer of experience, gender, and leg tested. SUBJECTS: Two experienced
      examiners (1 male, 1 female) and two inexperienced examiners (1 male, 1 female)
      tested 22 subjects with unilateral anterior cruciate ligament (ACL) pathology.
      METHODS: The leg with an ACL injury and the uninjured leg of each subject were
      evaluated by all four examiners within one test session using 67-N, 89-N, maximum
      manual, and active anterior drawer tests. RESULTS: Greater anterior displacement
      values were found in the legs with ACL injury than in the uninjured legs.
      Reliability estimates, as assessed by intraclass correlation coefficients (2,k)
      and measurement error (SEM), suggest that therapist experience may be a more
      important factor influencing reliability than gender. CONCLUSION AND DISCUSSION:
      Given the magnitude of the errors obtained for tests routinely conducted in the
      clinic using the KT-1000 arthrometer, we recommend that repeated measurements
      should be taken by the same examiners whenever possible. [Ballantyne BT, French
      AK, Heimsoth SL, et al. Influence of examiner experience and gender on interrater
      reliability of KT-1000 arthrometer measurements.

PMID- 7568391
TI  - Feature, phoneme, syllable or word: how is speech mentally represented?
AB  - Four experimental approaches frequently used in speech perception research are
      discussed with respect to their impact on word recognition models and their
      implicit assumptions on the mental representation of speech. These approaches are
      (1) reaction time experiments; (2) the procedure of click localisation; (3) the
      method of selective adaptation, and (4) the assessment of word similarities. The
      results of the studies vary as a function of the experimental procedure chosen.
      Phonetic features, single sounds, syllables and words as entities are
      alternatively favoured as primary perceptual units. A critical evaluation and an
      attempt at integrating the data lead to the assumption that the adult
      speaker/listener has different kinds of mental representation of speech at
      his/her disposal. Depending on the focus of perception, units of different sizes
      are primarily focused in the recognition process. This implies that the listener
      is able to modify his/her temporal analysis window to a certain extent.
      Nonetheless, as a default case, the syllable serves as the primary perceptual
      unit.

PMID- 7568392
TI  - A probable case of clicks influencing the sound patterns of some European
      languages.
AB  - In the history of various European languages (Latin, Spanish, English, Swedish,
      and various dialects of French) there are instances of the cluster mn appearing
      as mpn. There are philological controversies as to whether this 'epenthetic' p
      was actually pronounced or was just a learned hypercorrect spelling. I offer here
      a novel phonetic scenario supporting the claim that the p was pronounced and
      arose in a phonetically natural way: I posit that in the mn cluster there was
      temporal overlap of the m and n closures. The simultaneous labial and apical
      closure would create a pocket of air between them which, when the labial closure
      was released, would undergo a momentary rarefaction of pressure and thus be
      released with a click-like burst. Listeners would be likely to interpret this
      stop burst auditorily as a pulmonic [p] and this would be the basis of their own
      pronunciations.

PMID- 7568390
TI  - Standardizing low back management.

PMID- 7568393
TI  - Interactions of fundamental frequency contour and perceived duration in
      Norwegian.
AB  - This study investigates the influence of fundamental frequency (F0) contour on
      perceived vowel duration in Norwegian. In the first of four experiments, a
      falling vs. flat contour in short vs. long vowels in isolated monosyllables was
      shown to cause a perceptual lengthening of the vowel. Contrary to the
      expectations, embedding the monosyllables sentence-medially in experiment 2 did
      not turn the lengthening into a shortening effect. Also unexpectedly, a rising
      vs. flat contour did not influence perceived duration in monosyllables
      (experiment 3). Experiment 4 focused on falling as well as rising contours in
      disyllabic test words. Here, too, a lengthening effect was found only for a
      falling pattern. In parallel with experiment 2, the presence of the test word's
      second syllable did not turn perceptual lengthening into perceptual shortening.
      Comparison of the present results with data previously reported for German leads
      to the conclusion that the interaction of F0 contour and perceived vowel duration
      is language-specific and cannot be explained by assuming a universal
      psychophysical mechanism.

PMID- 7568394
TI  - Effect of fundamental frequency on medial [+voice]/[-voice] judgments.
AB  - Previous research has suggested that the direction of short-duration fundamental
      frequency (F0) perturbations following consonants helps to signal consonant
      [+voice]/[-voice] (abbreviated as [voice]) status. It has been proposed that the
      [voice] cue corresponds to the direction and extent of F0 perturbations relative
      to the overall intonation contour. A competing view, the low-frequency
      hypothesis, suggests that F0 participates in a more general way whereby low
      frequency energy near the consonant contributes to [+voice] judgments. Listeners
      identified multiple stimulus series, each varying in voice onset time and ranging
      from /aga/ to /aka/. The series differed in overall intonation contour as well as
      in the direction of F0 perturbation relative to that contour. Consistent with one
      version of the low-frequency hypothesis, the F0 value at voicing onset, rather
      than the relative direction of the F0 perturbation, was the best predictor of
      [voice] judgments.

PMID- 7568396
TI  - Explaining the dispersion of the single-vowel occurrences in an F1/F2 space.
AB  - The variability of the Finnish vowel occurrences on the F1/F2 chart was studied.
      Repetitions (n = 8 x 10 + 10 = 160) of two syllable types, /hVh/ and /tVt/,
      produced by a male speaker were analysed. The F1/F2 variability in both contexts
      was estimated. In the /hVh/ context, the phoneme targets were considerably more
      peripheral than in the /tVt/ contexts. In the /tVt/ context, the phoneme
      placements were nearer the upper left corner of the F1/F2 space in /u/, /o/, /a/,
      and /ae/. That is understandable on the basis of the alveolar tongue blade
      position: the tongue holds its position nearer the alveolar area during its
      movement from [t] to [V] and back to [t] compared to the [hVh] articulation. In
      the latter articulation, the tongue is free to move and the vowel reaches its
      ideal position. This interpretation was corroborated by means of the test items
      with an open syllable (/tVV/). In order to explain the variability of the
      repetitions in one context, the notion of auditory critical band window (CBW) was
      used. A CBW covers an area on the psychoacoustical F1/F2 plot that comprises 1
      bark on the F1 and F2 scales. Its modification CBW-F1 implies that a critical
      band is presented as a circle comprising the diameter of 1 bark according to the
      F1 scale. Practically all single F1/F2 points occur within the CBW-F1 circle. In
      most cases, the variability is smaller than one CBW-F1 circle, but we can
      consider that a greater amount of repetitions would yield a greater
      dispersion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568395
TI  - Determination of glottal excitation cycles in running speech.
AB  - The three-channel pitch determination algorithm (PDA) presented in this paper
      combines a short-term analysis PDA, which derives fundamental frequency via a
      periodicity criterion, and two time domain PDAs that determine the instants of
      glottal closure according to local signal criteria. The first of these algorithms
      correlates the speech signal with an estimate of the impulse response of the
      vocal tract; the second applies a neural network. The reliability of these time
      domain PDAs is increased by constraints on the range of F0 imposed by the short
      term analysis PDA. First results show that the algorithm can be applied to both
      accurate pitch period determination of running speech and voice quality
      measurements, particularly the measurements of voice jitter.

PMID- 7568397
TI  - Phonetic and phonological aspects of English affricate production in children
      with speech disorders.
AB  - In this paper we consider phonetic and phonological aspects of the English
      voiceless affricate /t integral of/ as it is realised by children with
      developmental speech disorders. The speakers described in the study have normal
      /t/ but disordered /integral of/ and /t integral of/. Using electropalatography
      (Reading EPG), we compare the stop and fricative phases of /t integral of/ to
      independent /t/ and /integral of/. This comparison shows that the place of
      articulation of /t integral of/ can be predicted from that of independent
      /integral of/. There is a strict requirement for the affricate's stop release to
      be homorganic with its fricative phase, irrespective of the place of articulation
      of independent /t/. Sometimes, there is also an observable coronal gesture during
      the stop phase of a dorsal affricate indicating the influence of independent /t/.
      This is predicted by phonological theories in which the affricate is related to
      both /t/ and /integral of/ but not by theories in which the affricate is merely
      the stop counterpart go /integral of/.

PMID- 7568398
TI  - Variability of lip and jaw movements in the speech of children and adults.
AB  - One purpose of the present study was to examine displacement variability of lower
      lip and jaw movements to determine whether sounds that are generally learned
      earlier and should, therefore, have been practiced more (e. g., stops and nasals)
      would be less variable than sounds that tend to develop later (e. g.,
      fricatives). It was also of interest to determine whether individual articulators
      such as the lower lip and the jaw show any differences in displacement
      variability, given that lower lip gestures may need to be more precise than jaw
      movements. Repetitions of several labial-initial, CVC stimuli embedded in short
      phrases produced by three groups of children (5-, 8-, and 11-year-olds) and a
      group of adults were examined to determine the variability of articulatory
      gestures. No evidence was found to suggest that fricatives were more variable
      than stops or nasals for any of the groups. For the children but not the adults,
      lower lip gestures tended to be more variable than jaw movements.

PMID- 7568400
TI  - Photochemical linkage of antibodies to silicon chips.
AB  - Antibodies and antigen binding fragments thereof were photochemically immobilized
      on surface-modified silicon chips of 5 x 5 mm size. Silicon surface-grafted
      diazirines and benzophenones formed covalent bonds with the immunoreagents on
      light activation. Photolithographic immobilization of monoclonal antibodies in
      aqueous media was achieved on silicon chips by activating surface-grafted
      benzophenones. The presence of bovine serum albumin during irradiation reduced
      nonspecific adsorption of the immunoreagents and retained the immunoactivity of
      the photoimmobilized molecules.

PMID- 7568399
TI  - Novel therapeutic and diagnostic applications of hypocrellins and hypericins.
AB  - Hypocrellins and hypericins, structurally related plant pigments isolated from
      Hypocrella bambuase and Hypericum respectively, are known photodynamic agents.
      This review summarizes certain significant advances in the photophysics,
      photochemistry and photobiology of these pigments in the last 2 years and
      discusses their prospects as novel therapeutic and diagnostic agents in the
      future. Recently, certain unique properties of hypocrellins and hypericins have
      been explored for a variety of therapeutic and diagnostic applications. In
      particular, substantial progress has been made in both anticancer and antiviral
      applications (especially anti-human immunodeficiency virus). The promising
      anticancer and antiviral results obtained both in vitro and in vivo have led to
      intensive investigation into their photo-physical and photochemical processes,
      especially kinetic studies of their intramolecular proton transfer. These
      compounds offer the potential for a highly sensitive fluorescent redox sensor for
      investigation of a variety of cellular events. The biomedical advances of
      hypocrellins and hypericins have been further promoted by significant progress in
      their chemical synthesis and the recent commercialization of hypocrellins A and B
      and hypericin.

PMID- 7568401
TI  - Photochemistry of acetylenic ketones in micellar solutions as studied by product
      yield-detected ESR and transient absorption techniques.
AB  - The electron spin resonance (ESR) spectra of the transient radical pairs in the
      photoreduction of 1,5-diphenyl-1,4-pentadiyn-3-one(I) and 1,3-diphenyl-2-propyn-1
      one(II) in sodium dodecyl sulfate (SDS) micellar solutions have been obtained by
      using the product-yield-detected ESR (PYESR) technique. The PYESR spectra,
      detected by tracing the microwave effect on the spin-adduct yield as functions of
      the magnetic field, show the ESR spectra of the ketyl radical of the ketone and
      SDS radical as the components of the radical pairs. In addition, the growth and
      the decay processes of the radical pair were observed through detecting the
      effect of microwave pulse as functions of the delay period between a laser pulse
      and the off and on time, respectively, of a microwave pulse. The absorption
      spectra of transient species have also been obtained by using the laser flash
      photolysis technique. Through the analysis of these data and molecular orbital
      calculations, the role of acetylenic groups in the photoreactivity of acetylenic
      ketones is discussed.

PMID- 7568402
TI  - Kinetics and mechanism of photocycloaddition of deoxyuridines to 2,3-dimethyl-2
      butene.
AB  - The mechanism of photocycloaddition of 2'-deoxyuridine (1a) and thymidine (1b) to
      2,3-dimethyl-2-butene (Bu) in acetonitrile by UV irradiation has been studied.
      The reciprocal quantum yield for the cycloaddition increased linearly with
      reciprocal concentrations of Bu in acetonitrile to give limiting quantum yields
      at infinite concentration of Bu as 0.030 and 0.0096 for 1a and 1b, respectively.
      This shows that the cycloaddition proceeds in a two-step mechanism between the
      triplet state of 1 and Bu through biradical intermediates. Addition of cis-1,3
      pentadiene quenched the reaction obeying the Stern-Volmer equation. The above
      quenching experiments and laser transient spectroscopy revealed that the triplet
      state of 1a reacts with Bu with much larger rate constant (1.3-1.6 x 10(9) M-1 s
      1) than that of 1b (4-5 x 10(7) M-1 s-1) reflecting larger steric hindrance
      exerted in the reaction of 1b than that of 1a.

PMID- 7568405
TI  - 193 nm light induces single strand breakage of DNA predominantly at guanine.
AB  - Irradiation of DNA with 193 nm light results in monophotonic photoionization,
      with the formation of a base radical cation and a hydrated electron (phi PI =
      0.048-0.065). Although > 50% of the photoionization events initially occur at
      guanine in DNA, migration of the "hole" from the other bases to guanine occurs to
      yield predominantly its radical cation or its deprotonated form. From sequence
      analysis, the data reveal that 193 nm light induces single strand breaks (ssb) in
      double-stranded DNA preferential 3' to a guanine residue. However, it has
      previously been reported that 193 nm light yields very low yields of ssb (< 2% of
      the yield of e-aq). The distribution of these ssb at guanine is nonrandom,
      showing a dependence on the neighboring base moiety. The efficiency of ssb
      formation at nonguanine sites is estimated to be at least one order of magnitude
      lower. The preferred cleavage at guanine is consistent with migration and
      localization of the electron loss center at guanine. It is argued that singlet
      oxygen and the photoionized phosphate group of the sugar moiety are not major
      precursors to ssb. At present, the mechanisms of strand breakage are not known
      although a guanine radical or one of its products remain potential precursors.

PMID- 7568403
TI  - Photo-CIDNP study of pyrimidine dimer splitting. I: Reactions involving
      pyrimidine radical cation intermediates.
AB  - The light-induced splitting of pyrimidine dimers was studied using the electron
      acceptor anthraquinone-2-sulfonate (AQS) as a photosensitizer. To this end,
      photochemically induced dynamic nuclear polarization (photo-CIDNP) experiments
      were performed on a series of pyrimidine monomers and dimers. The CIDNP spectra
      demonstrate the existence of both the dimer radical cation, which is formed by
      electron transfer from the dimer to the photoexcited sensitizer AQS*, and its
      dissociation product, the monomer radical cation. In spectra of 1,1'-trimethylene
      bridged cis, syn pyrimidine dimers, polarization is observed that originates from
      a spin-sorting process in the dimer radical pair. This points to a relatively
      long lifetime of the dimer radical cation involved, which is presumably due to
      stabilization by the trimethylene bridge. Polarization originating from a dimer
      radical pair is detected in the spectrum of trans,anti (1,3-dimethyluracil) dimer
      as well. The spectra of the bridged pyrimidines also demonstrate the
      reversibility of the dissociation of dimer radical cation into monomer radical
      cation, which is concluded from the observation of polarization in the dimer as a
      result of spin sorting in the monomer radical pair.

PMID- 7568407
TI  - Genetic and molecular analyses of UV radiation-induced mutations in the fem-3
      gene of Caenorhabditis elegans.
AB  - The utility of a new target gene (fem-3) is described for investigating the
      molecular nature of mutagenesis in the nematode Caenorhabditis elegans. As a
      principal attribute, this system allows for the selection, maintenance and
      molecular analysis of any type of mutation that disrupts the gene, including
      deletions. In this study, 86 mutant strains were isolated, of which 79 proved to
      have mutations in fem-3. Twenty of these originally tested as homozygous
      inviable. Homozygous inviability was expected, as Stewart and coworkers had
      previously observed that, unlike in other organisms, most UV radiation-induced
      mutations in C. elegans are chromosomal rearrangements of deficiencies (Mutat.
      Res. 249, 37-54, 1991). However, additional data, including Southern blot
      analyses on 48 of the strains, indicated that most of the UV radiation-induced
      fem-3 mutations were not deficiencies, as originally inferred from their
      homozygous inviability. Instead, the lethals were most likely "coincident
      mutations" in linked, essential genes that were concomitantly induced. As such,
      they were lost owing to genetic recombination during stock maintenance. As in
      mammalian cells, yeast and bacteria, the frequency of coincident mutations was
      much higher than would be predicted by chance.

PMID- 7568406
TI  - Exploratory photochemistry of 5-azido-8-alkoxy-substituted psoralens free and
      bound to DNA.
AB  - 5-Azido-8-alkoxy psoralens were synthesized. Laser flash photolysis (LFP: XeF,
      351 nm, 55 mJ, 17 ns) of the azides in acetonitrile or benzene solution produces
      the triplet nitrene and a small amount of ketenimine. Laser flash photolysis of
      the azides in methanol or aqueous solution cleanly produces the triplet nitrene.
      In aqueous solution containing highly polymerized calf thymus DNA, LFP produces a
      mixture of triplet nitrene and ketenimine corresponding to photolysis of free and
      bound psoralen, respectively. The two transients decay slowly but at different
      rates. Assignment of the transient spectra were secured by matrix EPR and UV
      visible spectroscopy. The triplet nitrene lifetime is the same in buffer and in
      the presence and absence of calf thymus DNA. The results explain why psoralen
      azides are unable to efficiently nick plasmid DNA pBR322 upon UV activation.

PMID- 7568408
TI  - Behavior outdoors and its effects on personal ultraviolet exposure rate measured
      using an ambulatory datalogging dosimeter.
AB  - We describe the construction of a small device incorporating a UVB (290-320 nm)
      sensor that can be worn on the lapel site or waistband and which is electrically
      coupled to a portable data logger carried in a trouser pocket or worn on a belt.
      The detector has an approximate cosine-weighted angular response and is linear
      over a wide dynamic range. It has a spectral sensitivity that follows closely the
      erythema action spectrum in the UVB region, is less than one order of magnitude
      greater than this action spectrum in the UVAII region (320-340 nm) and between
      one to two orders of magnitude greater in the UVAI region (340-400 nm). The
      instrument has been used to monitor variations in erythemally effective exposure
      rate that occurred during three outdoor activities with differing weather
      conditions. Erythemal irradiance incident on the trunk was recorded every 2 s for
      periods ranging from 1 to 2.2 h. The results demonstrated that behavior outdoors
      can be a more dominant factor in determining personal exposure than ambient
      ultraviolet and highlighted the very important role that shade from trees plays
      in reducing exposure.

PMID- 7568404
TI  - Photo-CIDNP study of pyrimidine dimer splitting. II: Reactions involving
      pyrimidine radical anion intermediates.
AB  - A series of photo-CIDNP (chemically induced dynamic nuclear polarization)
      experiments were performed on pyrimidine monomers and dimers, using the electron
      donor N alpha-acetyltryptophan (AcTrp) as a photosensitizer. The CIDNP spectra
      give evidence for the existence of both the dimer radical anion, which is formed
      by electron transfer from the excited AcTrp* to the dimer, and its dissociation
      product, the monomer radical anion. The AcTrp spectra are completely different
      from those obtained with an oxidizing sensitizer like anthraquinone-2-sulfonate,
      because of different unpaired electron spin density distributions in pyrimidine
      radical anion and cation. In the spectra of the anti (1,3-dimethyluracil) dimers,
      polarization is detected that originates from a spin-sorting process in the dimer
      radical pair, pointing to a relatively long lifetime of the dimer radical anions
      involved. Although the dimer radical anions of the 1,1'-trimethylene-bridged
      pyrimidines may have a relatively long lifetime as well, their protons have only
      very weak hyperfine interaction, which explains why no polarization originating
      from the dimer radical pair is detected. In the spectra of the bridged
      pyrimidines, polarized dimer protons are observed as a result of spin sorting in
      the monomer radical pair, from which it follows that the dissociation of dimer
      radical anion into monomer radical anion is reversible. A study of CIDNP
      intensities as a function of pH shows that a pH between 3 and 4 is optimal for
      observing monomer polarization that originates from spin-sorting in the monomer
      radical pair. At higher pH the geminate recombination polarization is partly
      cancelled by escape polarization arising in the same product.

PMID- 7568411
TI  - Interactions between N-aspartyl chlorin e6, detergent micelles and plasma
      lipoproteins.
AB  - Addition of plasma to the photosensitizing agent N-aspartyl chlorin e6 (NPe6) in
      Triton X-100 micelles results in a blue-shift of fluorescence emission,
      corresponding to a change in the average environmental dielectric constant from 8
      to 32. This effect was not observed with anionic or cationic detergents or with
      several other sensitizers including a close analog, chlorin e6. The
      apolipoprotein fraction of high-density lipoproteins (HDL) was found responsible
      for this blue-shift. These results indicate a highly selective interaction
      between HDL apolipoproteins and NPe6 molecules. Addition of the HDL
      apolipoprotein to NPe6 incorporated into Triton micelles decreased the fraction
      of NPe6 molecules accessible to Cd(2+)-induced fluorescence quenching but
      resulted in an increase in the Stern-Volmer quenching constant (an index of
      quenching efficiency).

PMID- 7568410
TI  - Spectroscopic and microscopic characteristics of human skin autofluorescence
      emission.
AB  - To improve the understanding of human skin autofluorescence emission, the
      spectroscopic and microscopic characteristics of skin autofluorescence were
      studied using a combined fluorescence and reflectance spectroanalyzer and a fiber
      optic microspectrophotometer. The autofluorescence spectra of in vivo human skin
      were measured over a wide excitation wavelength range (350-470 nm). The
      excitation-emission matrices of in vivo skin were obtained. An excitation
      emission maximum pair (380 nm, 470 nm) was identified. It was revealed that the
      most probable energy of skin autofluorescence emission photons increases
      monotonically and near linearly with increasing excitation photon energy. It was
      demonstrated that the diffuse reflectance, R, can be used as a first order
      approximation of the fluorescence distortion factor f to correct the measured in
      vivo autofluorescence spectra for the effect of tissue reabsorption and
      scattering. The microscopic in vitro autofluorescence properties of excised skin
      tissue sections were examined using 442 nm He-Cd laser light excitation as an
      example. It was demonstrated that the fluorophore distribution inside the skin
      tissue is not uniform and the shapes of the autofluorescence spectra of different
      anatomical skin layers vary. The result of this study confirms that the major
      skin fluorophores are located in the dermis and provides an excellent foundation
      for Monte Carlo modeling of in vivo autofluorescence measurements.

PMID- 7568409
TI  - Uptake kinetics and intracellular localization of hypocrellin photosensitizers
      for photodynamic therapy: a confocal microscopy study.
AB  - Hypocrellins are naturally occurring compounds with photosensitizing properties
      in biological systems. We have prepared synthetic derivatives of hypocrellin B,
      which have promise as photosensitizers in the clinical application of
      photodynamic therapy. The intracellular localization and uptake kinetics of
      hypocrellin B and several selected hypocrellin congeners were determined
      semiquantitatively by fluorescence confocal microscopy in monolayer cultures of
      EMT6/Ed murine tumor cells. Each compound had unique uptake kinetics. Although no
      compound tested to date has demonstrated nuclear labeling, most could be detected
      in lysosomes, Golgi, endoplasmic reticulum and, to a minor extent, in cellular
      membranes. No two compounds gave identical labeling distributions. The
      differences are assumed to originate in physicochemical properties characteristic
      of each compound, which may ultimately impact upon the primary modality of
      phototoxicity.

PMID- 7568412
TI  - Dual role of melanins and melanin precursors as photoprotective and phototoxic
      agents: inhibition of ultraviolet radiation-induced lipid peroxidation.
AB  - Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the
      main inducer of melanin pigmentation, the major protective mechanism of mammalian
      skin against radiation damage. The melanin pigments, eumelanin and pheomelanin,
      are likely to be important in protection against UVR, but their precursors are
      generally considered as phototoxic. The available data suggest DNA damage as the
      mechanism of phototoxicity. However, the effect of melanin precursors on membrane
      damage through lipid peroxidation, another important and probably more relevant
      (from the point-of-view of the melanosomal confinement of these molecules)
      mechanism of phototoxicity, not known. As a model system for UVR-melanin-membrane
      interactions, we irradiated liposomes in the presence of eumelanin, pheomelanin
      and two of their major precursors, 5,6-dihydroxyindole (DHI) and 5-S
      cysteinyldopa (SCD). The presence of the two melanin precursors substantially
      reduced the formation of lipid peroxidation products resulting from UVR exposure.
      The antioxidant activity of the melanin precursors was diminished under strong
      prooxidant conditions (presence of Fe3+). These results suggest that melanin
      precursors may have an important role in the protection of skin against the
      harmful effects of UVR including photocarcinogenesis.

PMID- 7568413
TI  - The effect of ALA and radiation on porphyrin/heme biosynthesis in endothelial
      cells.
AB  - To study porphyrin biosynthesis in human microvascular endothelial cells, HMEC-1
      cells, a transformed human microvascular endothelial cell line, were incubated
      with 5-aminolevulinic acid (ALA), the precursor of endogenous porphyrins, and
      porphyrin accumulation was measured spectro-fluorometrically. The HMEC-1 cells
      accumulated porphyrin in a concentration-related and a time-dependent fashion.
      Protoporphyrin was the predominant porphyrin accumulated in the cells. The effect
      of light on protoporphyrin accumulation was evaluated by exposing the ALA-loaded
      HMEC-1 cells to ultraviolet-A (UVA) and blue light, followed by another
      incubation with ALA for 2-24 h. Enhancement of protoporphyrin accumulation in
      irradiated HMEC-1 cells was observed 2-24 h after irradiation, which was
      associated with a decrease in ferrochelatase protein and activity. Porphyrin
      accumulation from ALA after irradiation was significantly decreased when catalase
      (750-3000 U/mL, 29.3-44.3% suppression) or superoxide dismutase (270 U/mL, 36.4%
      suppression) was present during irradiation. These data demonstrate that HMEC-1
      cells were capable of porphyrin biosynthesis, and that exposure of protoporphyrin
      containing HMEC-1 cells to UVA and blue light, which includes the Soret band
      spectrum, decreased the ferrochelatase activity and its protein. These changes
      were mediated, at least in part, by reactive oxygen species.

PMID- 7568414
TI  - Local anesthetics enhance nitric oxide production by human peripheral
      neutrophils.
AB  - Various neutrophil functions are suppressed by local anesthetics. We studied the
      effect of local anesthetics on nitric oxide (NO) generation in human peripheral
      neutrophils. Lidocaine and other local anesthetics stimulated NO generation in
      resting neutrophils. Canavanine, an NO synthase inhibitor, inhibited NO
      generation. Lidocaine and the other local anesthetics enhanced formylmethionyl
      leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA)-induced NO
      generation. These findings suggest that NO mediates various pharmacological
      effects of the local anesthetics on the host defense mechanism and the control of
      blood pressure.

PMID- 7568415
TI  - Proton NMR spectroscopic studies of serum as an aid to perioperative cellular
      metabolic monitoring.
AB  - Perioperative concentration changes of cellular metabolites in serum were studied
      by proton NMR spectroscopy in four cancer patients who underwent tumorectomies
      under general anesthesia. In proton NMR spectra of serum, the resonances
      assignable to fatty acid in lipoprotein, lactate, alanine, glucose, glycoprotein
      and other metabolites were observed. The concentrations of fatty acid and alanine
      did not show significant changes during the operations compared with those in
      healthy volunteers. The concentrations of lactate, glucose and glycoprotein
      increased during the operations above the concentration ranges in the control
      subjects. The time-course of concentration change for lactate, glucose and
      glycoprotein was roughly classified into two patterns: i) the maximums of lactate
      and glucose concentration were observed in the latter halves or at the ends of
      the operations; ii) the maximums of glycoprotein concentrations were observed
      three hours after the incision, regardless of the operative time. The results
      showed cellular metabolic changes became larger as the operations proceeded
      responding to surgical stress. Prompt cellular metabolic monitoring is
      indispensable for the screening of cellular metabolic disorders caused by
      excessive surgical stress and proton NMR spectroscopy can be a new tool for
      monitoring perioperative cellular metabolism.

PMID- 7568416
TI  - Increased excretion of taurine, hypotaurine and sulfate after hypotaurine loading
      and capacity of hypotaurine metabolism in rats.
AB  - Hypotaurine was intraperitoneally injected into rats and urinary taurine,
      hypotaurine and sulfate were determined. Taurine excretion increased dose
      dependently when 1 to 7 mmol of hypotaurine per kg of body weight was
      administered. The total excretion and the increased excretion (difference of
      those before and after the loading) were 2328 +/- 219 and 1948 +/- 153 mumol per
      kg of body weight per day, respectively, at 7 mmol of hypotaurine loading.
      Hypotaurine excretion was negligible in the normal rat urine. However, it
      increased when hypotaurine was loaded. Hypotaurine excretion at 7 mmol of
      hypotaurine loading was 2282 +/- 258 mumol per kg per day. These results indicate
      that the capacity of hypotaurine oxidation to taurine in rats is more than 2 mmol
      per kg per day under the present experimental conditions. Sulfate excretion
      increased significantly when more than 3 mmol of hypotaurine per kg of body
      weight was injected. When 5 and 7 mmol of hypotaurine was loaded, the increased
      excretion of sulfate was 619 +/- 205 and 632 +/- 118 mumol per kg per day,
      respectively. It was confirmed that in vitro incubation of hypotaurine and 2
      oxoglutarate with rat liver homogenate results in the formation of L-glutamate
      and sulfate. Present findings indicate that hypotaurine in vivo was mainly
      oxidized to taurine and that it was partly metabolized to sulfate via
      transamination reaction.

PMID- 7568418
TI  - Effect of lanthanides on tubulin polymerization.

PMID- 7568417
TI  - Thoughts over cell biology: a commentary.

PMID- 7568419
TI  - Selective inhibition of human TNF-alpha action by flecainide acetate, an
      antiarrhythmic drug.
AB  - It is now generally accepted that human tumor necrosis factor-alpha (hTNF-alpha)
      affects not only tumor cells but also normal cells, providing critical tissue
      damage. hTNF-alpha also enhanced the response of polymorphonuclear neutrophils
      (PMN) by its priming action and resulted in the increased generation of active
      oxygen which in turn may be responsible for the tissue injury. Seeking a
      conventional drug to attenuate the cytolytic activity of tumor necrosis factor
      (TNF-alpha) and thereby prevent excessive tissue injury, we focused on the
      cytolytic action of hTNF-alpha against L929 cells, which are sensitive to TNF
      alpha, and found that flecainide acetate [N-(2-piperidylmethyl) 1,5-bis-(2,2,2
      trifluoroethoxy) benzamide acetate] inhibited specifically the cytolytic action
      of hTNF-alpha against L929 cells. Flecainide acetate also specifically inhibited
      the priming action of hTNF-alpha which enhance the formylmethionyl-leucyl
      phenylalanine (FMLP)-induced receptor-mediated superoxide (O.2-) generation of
      human peripheral polymorphonuclear neutrophils (hPMN). The ID50 values for hTNF
      alpha induced cytotoxicity in L929 cells and hTNF-alpha primed FMLP-induced O.2-
      generation of hPMN were 30 and 50-60 microM, respectively. However, the drug does
      not inhibit the FMLP- or phorbol myristate acetate (PMA)-induced O.2- generation
      of nonprimed hPMN and has a weak cytotoxic effect on L929 cells. From these
      results, it is concluded that flecainide acetate suppressed specifically the
      action of hTNF-alpha.

PMID- 7568420
TI  - Membrane fluidization by animycotic bifonazole.
AB  - Calorimetry, nuclear magnetic resonance and X-ray diffraction techniques have
      been used to obtain thermodynamic and structural information on dipalmitoyl
      phosphatidylcholine (DPPC) liposomes doped by the antimycotic drug bifonazole in
      the range 0 < R < 1, where R = moles of bifonazole/moles of DPPC. The technique
      of spin labeling electron spin resonance (ESR) has also been used to study
      permeability and fluidity properties. The decrease of the cooperativity at the
      gel to liquid crystalline phase transition, as shown by ESR an DSC measurements,
      indicates that bifonazole imparts higher fluidity to the lipid matrix. Increase
      in permeability of ascorbate ions, after incorporation of bifonazole in the
      membrane, has been detected by ESR experiments using spin label 5-SASL. 13C NMR
      spectra indicate that the drug molecule is highly immobilized. X-ray diffraction
      and freeze fracture TEM results show that the equilibrated phase at room
      temperature is lamellar and unidimensional together with the presence of small
      particles and pits of uniform size. A marked hysteresis is evident in the
      formation of this phase.

PMID- 7568422
TI  - Dominance rank, cortisol concentrations, and reproductive maturation in male
      rhesus macaques.
AB  - Among adolescent male rhesus macaques, Macaca mulatta, the highest ranking
      individual within a cohort has higher testosterone concentrations at a younger
      age, earlier in the mating season, and for a longer duration than his lower
      ranking conspecifics. We sought to determine whether such a rank-related pattern
      of reproductive maturation could be a function of differences in glucocorticoid
      levels. A 2-yr longitudinal study of a cohort of adolescent males living in a
      heterosexual group in a one acre outdoor enclosure revealed no differences in
      cortisol concentrations between high and low status males. Cortisol was not
      inversely correlated with testosterone in either adolescent or adult males. Young
      pubescent males had increases in cortisol levels coincident with maturation,
      while older adolescent males had cortisol concentrations comparable to those of
      adult males. Low ranking males tended to have more variable cortisol
      concentrations across time. We conclude that cortisol concentrations are not a
      function of dominance status and that the timing of reproductive maturation in
      male rhesus macaques is independent of cortisol concentrations.

PMID- 7568421
TI  - Sex differences and effects of social cues on daily rhythms following phase
      advances in Octodon degus.
AB  - Two experiments were designed to determine whether social cues could enhance the
      rate of resynchronization in body temperature and general activity rhythms in
      male or female Octodon degus following a 6 h phase advance. The first experiment
      examined average resynchronization rates for animals in each condition. The
      second experiment examined resynchronization rates for a smaller group of
      animals, each treated as its own control. Female phase-shifters resynchronized
      temperature and activity rhythms significantly faster when housed with an
      entrained (donor) female than those females housed with another phase-shifting
      female or housed alone. Females housed with entrained males resynchronized their
      temperature rhythms significantly slower than females housed with entrained
      females. No differences in resynchronization rate for phase-shifting males
      existed between test conditions. However, activity rhythms of male controls
      (housed alone) reentrained significantly faster than those of female controls.
      These experiments demonstrate a sex difference in (i) reentrainment rate by
      photic cues alone; (ii) donors' effect on female phase-shifters'
      resynchronization; and (iii) phase-shifters' resynchronization response to donor
      cues. In these studies, resynchronization in the presence of another animal could
      either have been achieved by entrainment of the pacemaker or by masking of the
      circadian rhythms.

PMID- 7568423
TI  - Temporary increase of plasma epinephrine affects stress responses 24 h later.
AB  - The impact of temporary (24 h) implantation of epinephrine tables on
      catecholamine responses to handling and immobilization 24 h later was
      investigated in rats. Free plasma epinephrine responded with an increase to both
      types of stress (77% and 326%, respectively) while controls showed a weaker
      response to immobilization. The basal level of free plasma norepinephrine was
      reduced (46% vs. controls) after epinephrine pretreatment, but neither handling
      nor immobilization had a specific effect on this parameter. In contrast, the
      basal level of free plasma dopamine was increased after epinephrine pretreatment
      (183%); however, as with free norepinephrine, there was no specific effect of
      handling or immobilization. Conjugated plasma epinephrine was significantly
      lowered after epinephrine pretreatment (44% vs. controls). It did not respond
      specifically to handling or immobilization except for a stronger response after
      20 min of immobilization. Conjugated norepinephrine showed no specific response,
      but increased nonspecifically after extended immobilization. Conjugated dopamine
      was lowered (30%-48%) in the E-treated group and did not respond to stress at any
      time. Thus, a temporary elevation of free plasma epinephrine affected,
      differentially, basal levels and stress responses of free and conjugated
      catecholamines 24 h later.

PMID- 7568424
TI  - Feeding patterns of lactating cows of three different breeds fed hay, corn
      silage, and grass silage.
AB  - Feeding behavior of 35 lactating cows of three different breeds (Holstein
      Friesian = HF, Simmental = SI, and Jersey = JER) was compared in the present
      study. The cows were kept in a loose housing system and fed hay, corn silage (CS)
      and grass silage (GS) ad lib. Within 7 consecutive days, 2918 meals were recorded
      and analyzed: 2503 meals were eaten during the light phase (0430-2200), and 57%
      of these diurnal meals consisted of only one feedstuff (43% hay, 9% CS, 5% GS).
      During the dark phase, only 23% of the 415 meals consisted of hay alone, but 16%
      of CS and 21% of GS alone. This circadian distribution showed no breed
      differences, yet meal patterns did: HF and SI cows ate 11 meals per day, and JER
      cows ate more than 13 meals/day. Meal size was 9.8MJ, 7.9MJ, and 5.8MJ for HF,
      SI, and JER cows, respectively. HF cows had the highest 24 h energy intake and
      JER cows the lowest, but the latter spent the most time feeding. During the light
      phase all three breeds obtained the most energy from hay, followed by CS and GS.
      In contrast, during the dark phase most energy was derived from GS, and hay
      contributed the least. A significant premeal correlation was observed for cows of
      all breeds, in particular during the time with the highest feeding activity (0800
      1300). During the dark phase no premeal correlation could be detected; instead a
      significant postmeal correlation appeared, in particular in HF and SI
      cows.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568426
TI  - Effect of occluding the pylorus on intraoral intake: a test of the gastric
      hypothesis of meal termination.
AB  - Meal size does not change in response to food being restricted to the stomach by
      occlusion of the pylorus. This result has been used as evidence for a gastric
      model of meal termination where feedback arising solely from the stomach is taken
      to underlie satiation. Such data provide support for the gastric model, however,
      only if the rate of gastric emptying during ingestion in the unoccluded condition
      is slow, such that comparable amounts of food would be found in the stomach at
      the end of the meal in both the pylorus-occluded and unoccluded conditions. To
      evaluate this tissue directly, rats were implanted with pyloric cuffs and gastric
      cannulas and given an intraoral intake test of a 10.5% glucose solution with
      either the pylorus occluded or unoccluded. At the end of each intraoral intake
      test, the content of the stomach was removed via the gastric cannula and it's
      volume and concentration measured. Occlusion of the pylorus did not change meal
      size, but both the volume and grams of glucose solute found in the stomach were
      substantially greater in the pylorus-occluded condition. These results are not
      consistent with the hypothesis that the stomach is the sole source of inhibitory
      signals that terminate a meal. Cumulative intake would appear to be accurately
      tracked regardless of its distribution within the digestive tract.

PMID- 7568425
TI  - Fever and the acute elevation in whole-body thermogenesis induced by lateral
      hypothalamic lesions.
AB  - Three studies investigated the role of fever in the acute elevation of heat
      production induced by lateral hypothalamic (LH) lesions and the mechanisms by
      which this thermogenic response can be attenuated by reductions in body weight.
      In Study 1, reducing the weights of rats prior to lesioning the LH attenuated
      both the usual postlesion fever and elevation in thermogenesis. In Study 2,
      blocking prostaglandin synthesis with indomethacin likewise blunted both the
      lesion-induced fever and thermogenesis. In Study 3, treating already weight
      reduced rats with indomethacin attenuated, but still failed to eliminate, the
      lesion-induced fever. Together, these results suggest that both the fever and
      increased thermogenesis induced by LH lesions are mediated, at least in part, by
      prostaglandin mechanisms which themselves are influenced by body energy status.

PMID- 7568427
TI  - Nitrous oxide induces feeding in the nondeprived rat that is antagonized by
      naltrexone.
AB  - Three experiments investigated a possible effect of nitrous oxide (N2O) on food
      intake in nondeprived male hooded rats in independent groups designs. Experiment
      1 demonstrated a concentration-related increase in intake with increasing level
      of nitrous oxide (10-40% N2O), reaching statistical significance at 20% N2O when
      compared to room air controls (p < 0.05). In experiment 2, pretreatment with 10
      and 20 mg/kg of the benzodiazepine antagonist, flumazenil, failed to
      significantly attenuate 30% N2O-induced hyperphagia. In Experiment 3,
      pretreatment with the opioid antagonist, naltrexone, effectively antagonized 30%
      N2O-induced hyperphagia. Pronounced attenuation (to 59% of 30% N2O-induced intake
      level over a 1 h period) at the lowest dose of naltrexone (0.1 mg/kg, p < 0.01)
      compared to vehicle level resulted in a shallow dose-response curve across the
      dose range tested (0.1-10.0 mg/kg). These results suggest that an endogenous
      opioid mechanism is prominently involved in the N2O-induced ingestive response.

PMID- 7568428
TI  - Locomotor activity and utilization of energy reserves during fasting after
      ventromedial hypothalamic lesions.
AB  - The ventromedial hypothalamus (VMH) is known to be involved in the regulation of
      energy metabolism but it may also modulate locomotor activity. Since prolonged
      fasting is marked by a succession of changes in energy utilization and locomotor
      activity, it was hypothesized that VMH may be a critical link controlling
      mobilization of energy stores and/or behavioral changes in response to fasting.
      To test this, the changes in rate of body mass loss, body content in lipid and
      protein, and wheel-running activity were studied in fasted nonobese rats with VMH
      electrolytic lesions. Secondary effects of VMH obesity were ruled out by
      postoperative restricted feeding. During fasting, VMH lesions impaired neither
      the overall lipid mobilization nor the late rise in daily body mass loss,
      concomitant with the increase in net proteolysis. Despite that the onset of this
      late stage of fasting was significantly delayed in VMH vs. sham-operated rats (13
      +/- 1 vs. 8 +/- 1 days, respectively), the final amount of reserve lipids (3 g)
      was closely similar in both groups: this is the first experimental evidence of
      the hypothesis of a lipidic set-point. These results indicate that VMH is not a
      critical link controlling the time-course of utilization of energy reserves. The
      increase in diurnal (and total) daily wheel-running observed in fasted sham
      operated rats still occurred in fasted VMH rats but was significantly reduced and
      delayed. VMH nuclei and/or associated fibers are therefore involved in the
      fasting-induced rise in diurnal activity.

PMID- 7568429
TI  - Cyanide induced aversions in the possum (Trichosurus vulpecula): effect of route
      of administration, dose, and formulation.
AB  - Possums (Trichosurus vulpecula) are New Zealand's main vertebrate pest. Control
      practices using poisons are likely to remain the most cost effective methods for
      the immediate future but poisons may be avoided in the field. A series of
      experiments were conducted to determine whether cyanide bait avoidance involved
      conditioned food aversions (CFA) induced by sublethal cyanide ingestion. Food
      aversions were conditioned in three experiments using intraperitoneal or oral
      routes of administration with three different cyanide formulations over a range
      of doses. Across all experiments there was a direct relationship between dose and
      the proportion of animals developing CFAs. When administered orally, doses
      greater than 5 mg/kg resulted in more than 50% of surviving animals developing
      aversions. Route of administration or formulation appeared to have no
      differential effect on development of CFA. Although there was considerable
      variation between individuals in the degree of aversion shown this may be one
      mechanism that could account for poor possum kill rates in some poisoning
      operations.

PMID- 7568430
TI  - Differential audiogenic seizure sensitization by selective unilateral substantia
      nigra lesions in resistant Wistar rats.
AB  - Evaluation of the participation of different substantia nigra sites in the
      sensitization of resistant (R) animals to audiogenic seizures (AS), was performed
      after series of small (5 mC; n = 28), medium (10 mC; n = 57) and large (15 mC; 3
      points of 5 mC each, n = 19) unilateral electrolytic lesions of the substantia
      nigra (SN) in R rats. Animals were evaluated at 5, 10, 15, and 30 days post
      surgery and behavior was measured by a neuroethological method. Small unilateral
      lesions induced AS susceptibility in 14% R animals with 3% of them displaying
      tonic-clonic AS. Medium sized lesions induced AS susceptibility in 50% of the
      animals with 18% of these exhibiting tonic-clonic seizures similar to those
      displayed by naturally susceptible (S) animals, but with predominance of wild
      running (gyri, jumping and atonic falling) contralateral to the lesioned SN. AS
      severity was significantly higher at day 5 postsurgery, decreasing at days 10, 15
      and 30. Large unilateral lesions destroying the entire SN failed to cause tonic
      clonic seizures although wild running occurred in 10% of the animals. Bilateral
      large SN lesions (15 mC; n = 24) did not modify AS severity in S animals, but
      only induced a statistically significant increase in the AS latency. The present
      data suggest: (i) AS severity after SN lesions is not a linear function of the
      lesion size; (ii) functionally different and antagonistic AS related substrates
      may exist in the SN; (iii) neurochemical and hodological characterization of
      these areas should be important for a better understanding of their role in AS.

PMID- 7568431
TI  - Chronic Losartan treatment blocks isoproterenol-induced dipsogenesis.
AB  - Previous studies suggest that beta-adrenergic receptor agonists and other
      hypotensive agents stimulate water intake via the renin-angiotensin system (RAS).
      However, a recent study reported that acute peripheral administration of
      Losartan, an angiotensin II (AII) type I receptor antagonist, failed to inhibit
      isoproterenol-induced water intake. In the current study we assessed the role of
      chronic Losartan treatment on isoproterenol-induced water intake. Male Sprague
      Dawley rats were divided into two groups (n = 10/group). The experimental group
      was chronically treated with Losartan in the drinking water (120 mg/kg/day). Rats
      in the control group were maintained on normal tap water. At the end of each
      week, water intake in response to isoproterenol was determined. On the days of
      the dipsogenic study, water intake was determined 1 h prior to and 2 h following
      SC injection of isoproterenol (25 micrograms/kg). Isoproterenol-induced water
      intake in the experimental group was significantly lower than the control rats by
      71% and 88% at the end of weeks one and two respectively (p < 0.01). Following
      ten days of Losartan treatment, dipsogenic response to AII likewise demonstrated
      a complete blockage of AII receptors (75% decrease compared to the controls).
      These data strongly suggest that water intake in response to isoproterenol is
      mediated in part by the RAS.

PMID- 7568433
TI  - Taste quality profiles for fifteen organic and inorganic salts.
AB  - Biophysical studies of isolated taste receptor cells show that one transduction
      mechanism for Na+ salts involves the inward movement of Na+ through an apical ion
      channel, which is sensitive to the diuretic amiloride. An additional paracellular
      pathway also appears to be involved in NaCl transduction, but not in the
      transduction of organic Na+ salts. Little is known, however, about how these
      receptor mechanisms relate to taste perception. Recent human psychophysical
      studies suggest that the amiloride-sensitive transduction pathway is coupled to
      the sour side taste of these salts rather than to their saltiness. In the present
      study, we employed direct magnitude estimation of taste intensity and quality of
      fifteen organic and inorganic Na+, Li-, K+, and Ca+2 salts. Many salts had
      multiple taste qualities, such as the salty and bitter tastes of NH4Cl and KCl;
      the Ca+2 salts were predominantly bitter. Taste quality often changed with
      stimulus concentration. Multivariate analyses of their taste profiles resulted in
      a grouping of these 18 stimuli within a taste space bounded by NaCl, sucrose,
      citric acid, and QHCl, with the organic salts positioned between NaCl and citric
      acid. The organic Na+ salts and the Li+ salts were considerably less salty and
      proportionately more sour than NaCl. These results, combined with previous work
      showing that amiloride suppresses the sourness of NaCl and Na-gluconate, predict
      that the organic Na+ salts and the Li+ salts would be more greatly suppressed by
      amiloride treatment than would NaCl.

PMID- 7568432
TI  - Taste and smell losses in HIV infected patients.
AB  - Human immunodeficiency virus (HIV-1) associated wasting is an increasingly common
      clinical manifestation of AIDS. The pathogenesis of wasting is multifactorial and
      includes reduced caloric intake as a major contributing mechanism. The
      perceptions of taste and smell play an important role in stimulating caloric
      intake and in optimizing nutrient absorption through cephalic phase reflexes. The
      purpose of this study was to evaluate the degree of losses in taste and smell
      function that occur in subjects infected with HIV. Taste and smell function was
      evaluated in 40 HIV infected individuals and 40 healthy control subjects matched
      for age, sex, race, smoking behavior, and number of years of education.
      Chemosensory tests administered to subjects included taste and smell detection
      thresholds, taste and smell memory tests, taste and smell discrimination tests,
      and taste and smell identification tasks. Significant differences were observed
      between experimental and control subjects in glutamic acid taste detection
      threshold (p < 0.001), quinine hydrochloride taste detection threshold (p <
      0.001), menthol smell detection threshold (p < 0.001) and in the taste
      identification task (p = 0.006). Overall the results suggest abnormalities in the
      peripheral and central nervous systems, and subjective distortion of taste and
      smell. A significant correlation was not established between CDC classification
      of HIV infection and taste and smell function, although trends were observed
      suggesting worsening function with progression of HIV disease. These results
      document significant taste and smell losses in HIV infected subjects which may be
      of clinical significance in the development or progression of HIV associated
      wasting.

PMID- 7568434
TI  - Concurrent blockade of beta-adrenergic and muscarinic receptors disrupts working
      memory but not reference memory in rats.
AB  - In order to clarify the interactions between monoaminergic and cholinergic
      systems in working and reference memory functions, the effects of administration
      of the alpha, beta-adrenergic, D1-, D2-dopaminergic or serotonergic receptor
      antagonist together with the muscarinic receptor antagonist scopolamine on this
      behavior were examined using a three-panel runway task. Both in working and
      reference memory tasks, the number of errors (attempts to pass through two
      incorrect panels of the three panel-gates at four choice points) was
      significantly increased by 0.32 mg/kg scopolamine, but not by the doses up to
      0.18 mg/kg. The beta-adrenergic antagonist propranolol at 10 mg/kg had no effect
      on the number of working memory errors. Combined administration of 10 mg/kg
      propranolol and scopolamine at 0.1 and 0.18 mg/kg significantly increased the
      number of working memory errors. However, in a reference memory task, propranolol
      at 10 mg/kg did not affect the number of errors, whether administered alone or
      together with 0.1 mg/kg scopolamine. Other monoaminergic receptor antagonists,
      including the alpha-adrenergic antagonist phentolamine (3.2 and 10 mg/kg), D1
      antagonist SCH23390 (0.032 and 0.056 mg/kg). D2-antagonist sulpiride (100 mg/kg)
      and serotonin antagonist cinanserin (10 and 32 mg/kg) had no significant effect
      on working or reference memory errors, whether they were administered
      independently or in combination with scopolamine at 0.1 mg/kg. These results
      suggest that beta-adrenergic/muscarinic interactions play an important role in
      mediating processes involved in working memory performance of rats.

PMID- 7568436
TI  - Successful intermale aggression and conditioned place preference in mice.
AB  - This study assessed the reinforcing properties of successful intermale agonistic
      encounters between OF1 male mice using the conditioned place preference paradigm.
      A three compartment apparatus was used and the procedure consisted of three
      phases: preconditioning (3 days), conditioning (8 days) and postconditioning (3
      tests). Individually housed male mice were allocated to two groups. The
      aggression group confronted docile opponents in the preconditioning "less
      preferred" compartment and were left alone in the "preferred" one. The control
      group was left alone in both compartments. Whereas no significant differences
      were found between both groups in the time spent in the less-preferred
      compartment, a separate analysis of animals in function of the color of the less
      preferred compartment revealed a clear-cut difference. Mice developed a
      conditioned place preference for the aggression-paired compartment only if that
      experience took place in the black one. These findings suggest that the process
      of establishing a conditioned place preference with successful intermale
      aggression as reinforcer is extremely fragile and can be easily disrupted by
      changing the environmental cues involved.

PMID- 7568435
TI  - Social discrimination procedure: an alternative method to investigate juvenile
      recognition abilities in rats.
AB  - Experiments were performed to establish the social discrimination procedure as an
      alternative method to the widely used social recognition test for investigating
      short-term olfactory memory processes in rats. The time that 4-mo old male
      animals spent investigating conspecific juveniles was taken as an index of their
      juvenile recognition/discrimination abilities. When the same juvenile was
      reexposed to the adult 30 min after its initial exposure, it was investigated at
      a significantly lower intensity compared to a simultaneously presented novel
      juvenile. If the second exposure to the previously exposed juvenile occurred 2 h
      later, however, both juveniles were investigated equally, indicating an
      extinction of olfactory memory. The simultaneous presentation of the previously
      exposed juvenile and novel juvenile provides not only an internal control under
      identical experimental conditions (thus reducing the number of sessions for a
      given experimental series), but also the opportunity to separate specific (i.e.,
      memory-related) from nonspecific (i.e., investigatory behavior-suppression)
      effects in pharmacological studies. Furthermore, the social discrimination
      procedure enables even in sexually naive adult male rats the detection of
      juvenile recognition abilities which seem to be masked in the social recognition
      test by sexual/aggressive behavior-motivated investigation. The method described
      here might be an attractive alternative to the conventional social recognition
      procedure.

PMID- 7568437
TI  - Nycthemeral variation in thermal dehydration-induced thirst.
AB  - Temporal variation in spontaneous water intake in rats is well established but
      little is known about temporal variation in water intake following dehydration.
      In the present study different male Sprague-Dawley strain rats were exposed
      without water for 3 h to either a 25 degrees C or a 40 degrees C environment
      every 4 h for 20 h. The rats were then allowed access to water in a 25 degrees C
      environment for 2 h. Rats exposed to 25 degrees C showed significant temporal
      variation in evaporative water loss, urine output, urine sodium and potassium
      excretion, water intake, and percent rehydration with higher values occurring
      during the night. Rats exposed to 40 degrees C had greater evaporative water
      loss, urine sodium excretion, feces output and water intake than the rats exposed
      to 25 degrees C and had temporal variations which were similar to those of the
      rats exposed to 25 degrees C. The robust effects of thermal-dehydration on water
      balance in rats are additive to rather than interactive with the effects of time
      of day.

PMID- 7568438
TI  - Interactive effect of food deprivation and agonistic behavior on blood parameters
      and muscle glycogen in pigs.
AB  - Agonistic behavior, neuroendocrine and plasma metabolite changes, and muscle
      glycogen content were studied in 16 fed and 16 24 h-fasted domestic Large White
      pigs (100 +/- 5 kg) submitted to dyadic encounters (30 min) in a novel
      environment. Comparisons were made with corresponding control pigs (eight fed and
      eight 24 h-fasted animals) kept under resting conditions. At rest, fasting
      resulted in a significant decrease in plasma insulin, increase in plasma-free
      fatty acids, and decrease in glycogen content in the predominantly red
      Semispinalis muscle. Fasted pigs displayed significantly more submissive acts
      than fed ones. In response to dyadic encounters, fed and fasted pigs showed
      similar rise in plasma levels of cortisol, catecholamines, and lactate, but
      stress-induced hyperglycemia was suppressed in food-deprived animals. Fasting
      enhanced stress-induced glycogen depletion in the predominantly white Longissimus
      muscle but this effect was significant only in fast-twitch glycolytic fibres
      (alpha W). In the Semispinalis of fasted pigs, however, dyadic encounters did not
      induce further glycogen depletion. The present findings suggest that in response
      to dyadic encounters, fasting-induced changes in glucose metabolism lead to a
      higher dependence on endogenous energy reserves, i.e., glycogen, in working
      muscles.

PMID- 7568439
TI  - Mikro-knemometry: an accurate technique of growth measurement in rats.
AB  - A novel, noninvasive technique for accurate measurements is presented which
      determines the distance between knee and heel of the rear lower leg in the
      conscious rat (mikro-knemometry). Each measurement consists of initially six,
      later four subsequent and independent estimations of this distance. During a 14
      day training study, the mean standard deviation (technical error) of five (six
      minus the first estimation) decreased from 196 microns to 101 microns.
      Measurements at exact 24-h intervals revealed nonlinear increments of rat lower
      leg growth, with marked infradian variation once every four to six days, similar
      to "mini growth spurts", described in rabbit and human growth. There was also a
      significant circadian periodicity of leg length increment (p < 0.01), with a
      minimum leg increment (after midnight dip) between 2400 h and 0300 h (mean: 4.8%
      (SEM 2.3%) of the total 24-h increment, p < 0.01), and a maximum increment (early
      morning spurt) between 0600 h and 0900 h (mean: 34.9% (SEM 2.5%) of the total 24
      h increment, p < 0.001). Thus, the technique of mikro-knemometry seems to be a
      useful tool for the investigation of longitudinal growth in laboratory rats, and
      may replace conventional techniques of growth measurements such as measuring body
      weight, nose-tail, or tail length.

PMID- 7568440
TI  - Body temperature, motor activity, and feeding behavior of mice treated with beta
      chlornaltrexamine.
AB  - The effects of an irreversible long term opioid antagonism on circadian rhythms
      in body temperature (Tb), locomotor activity (Act) and feeding under normal
      conditions and following lipopolysaccharide administration (LPS; 2.5 mg/kg) have
      been investigated in unrestrained mice housed at their thermoneutral zone (30
      degrees C). beta-chlornaltrexamine (beta-CNA; 5 mg/kg) given intraperitoneally
      decreased Tb on the day of injection, depressed Act, and reduced food and water
      intake for several days. The drug destroyed circadian rhythm in Tb for 4
      consecutive days after administration due to prevention of the night time
      increases in temperature, whereas mean day time Tb of mice treated with beta-CNA
      remained similar to controls. Between days 5-8 the day-time Tb of beta-CNA
      injected mice decreased, and the mice started displaying regular daily variations
      albeit with smaller amplitude and at lower level than controls. The depressive
      effect of beta-CNA on circadian variation in activity was more prolonged than its
      effect on Tb suggesting that these two variables are independently regulated.
      beta-CNA prevented the febrile response of the mice to LPS and enhanced the
      hypophagic effect of LPS. We conclude that normal circadian rhythms in Tb and
      Act, as well as certain symptoms of sickness behavior, have an opioid component.

PMID- 7568441
TI  - Disguised protein in lunch after low-protein breakfast conditions food-flavor
      preferences dependent on recent lack of protein intake.
AB  - As in the conditioning of appetite for protein in the rat, human preference for
      and intake of a food at lunch was increased when the flavor of that food was
      paired with an adequate supply of protein, following a breakfast lacking in
      protein. Men and women rated their preferences for two flavors in tasted foods
      (soup and cornflour dessert) on test days before and after a day when one flavor
      was eaten in very low protein food and another day with a different flavor eaten
      in food containing protein, but with minimal sensory differences between these
      foods. Subjects given a low-protein drink preload preferred the protein-paired
      flavor, while those receiving a high-protein drink did not. In a second
      experiment, preferences were measured by intake as well as ratings, and the
      difference in amount of protein between high- and low-protein lunches was
      increased. By both measures, relative preference for high-protein-paired dessert
      flavors increased from before to after pairing. The increase in intake preference
      ratio for the protein-paired flavor was abolished by a high-protein preload.
      Thus, people have a learning mechanism whereby a lack in protein intake comes to
      cue the selection of protein-rich foods that are not known to be such, and/or
      loading with protein might trigger avoidance specifically of a high-protein diet.

PMID- 7568442
TI  - Physiological and subjective responses to food cues as a function of smoking
      abstinence and dietary restraint.
AB  - Dietary restraint is a characteristic associated with greater increase in food
      intake after smoking cessation, and salivation is a marker of physiological
      responsiveness to food that may be influenced by cessation. The present study
      examined the effect of brief smoking abstinence (16 h) vs. no abstinence on
      salivary and subjective responses to food taste cues in women smokers high vs.
      low in dietary restraint (n = 10 each). On each of two days (smoking abstinence
      vs. nonabstinence), salivary volume was assessed during each of 10 trials
      involving presentation of a small sample of strawberry yogurt. Decline in
      salivation over trials is indicative of habituation, or reduction in
      physiological responsiveness to taste cues, and may be a marker of satiety.
      Subjects also completed self-report measures of hunger, taste liking, desire for
      cigarette, and emotional arousal during each trial. A 10-min period of ad lib
      consumption of yogurt ended each session. Results showed significantly elevated
      salivary response to the first trial of taste exposure in high vs. low restraint
      women, especially on the smoking day. Moreover, salivary habituation was
      significantly disrupted by smoking abstinence, especially over the first 5
      trials, in high restraint but not low restraint women. High restraint women also
      reported increasing desire for cigarette and emotional arousal across food taste
      trials on both days, while low restraint women reported no change in each over
      trials. There were no differences in ad lib yogurt consumption. These results
      indicate that brief smoking abstinence attenuates salivary habituation to taste
      in high restraint women, suggesting a marker for processes responsible for
      increased food intake after quitting smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568443
TI  - Effect of continuous infusion of lysine via different routes and hepatic vagotomy
      on dietary choice in rats.
AB  - The effect of continuous L-lysine (Lys) infusion on dietary choice between Lys
      deficient and protein-free diets in Sprague-Dawley rats was studied to determine
      the sensing site of Lys deficiency. After daily intake of each diet became
      constant, Lys was continuously infused for 11 days via intraperitoneal (IP),
      intragastric (IG) or intracerebroventricular (ICV) route, with an osmotic pump.
      Daily intake of each diet was measured. Intake of the Lys deficient diet compared
      with protein-free diet in either IP or IG Lys-infused group increased
      significantly (p < 0.001) vs. the intake in the baseline period. The selection of
      the Lys deficient diet was quite comparable between IP and IG groups. But the
      intake of the ICV group was unchanged. Hepatic vagotomy during IP infusion
      transiently delayed selection of the Lys deficient diet. These results imply the
      roles of postabsorptive mechanisms in sensing an amino acid deficiency, and
      possible involvement of the hepatic branch of the vagus in the sensing. However,
      sensing in the brain or indeed in the intestine was not excluded.

PMID- 7568444
TI  - Failure of intrabulbar and peripheral administration of N omega-nitro-L-arginine
      to prevent the formation of an olfactory memory in mice.
AB  - The gaseous neurotransmitter molecule nitric oxide (NO) has recently generated a
      lot of interest on account of its possible physiological role in several models
      of learning and memory, both in vitro and in vivo. The presence of its
      synthesizing enzyme has been reported in the granule cell and external plexiform
      layers of the accessory olfactory bulb (AOB) in mice and rats. We have tested the
      effect of different doses of the nitric oxide synthase inhibitor, N omega-nitro-L
      arginine applied locally and peripherally, on the formation of olfactory
      recognition memory in the context of pregnancy block in mice. Local infusions of
      5, 10, and 40 nmol of the NOS inhibitor into the AOB failed to prevent memory
      formation of the stud male without affecting the effectiveness of the strange
      male to induce pregnancy block. Peripheral administration of the NOS inhibitor
      produced a pregnancy block rate that was linearly related to the dose regardless
      of whether or not exposure to the familiar or no male subsequently followed. This
      suggests that the effect of peripheral administration of the NOS inhibitor on
      memory formation could not be assessed using this experimental paradigm. The
      observations made in this study do not enable us to envisage any critical or
      primary physiological role for NO in this memory model. Its role, at best, may be
      modulatory and not obligatory.

PMID- 7568445
TI  - Nutritional status and behavior during lactation.
AB  - Effects of chronic maternal food restriction and time of day on maternal and pup
      behaviors were examined in ovariectomized Sprague-Dawley rats (n = 26). Dams were
      fed ad lib (AL) or were restricted to 85% (85 AL) or 70% (70 AL) of ad lib
      intake. Dams and their 5-pup litters were observed for 45 min at night on days 9,
      14, and 19 of lactation and during the day on day 14. A novel behavioral
      instrument was used to observe maternal and pup behaviors. At night, food
      restricted animals engaged in more nursing behaviors than AL animals.
      Differential pup stimuli may account for this difference. AL animals engaged in
      more nursing behaviors during the day than night, whereas 70 AL animals
      demonstrated the opposite diurnal pattern. Time of feeding may explain this
      difference. On the other hand, 85 AL animals behaved similarly during the day and
      at night. Therefore, alterations in circadian behavior patterns are less
      pronounced in rats mildly restricted (85 AL) than in rats more food restricted
      (70 AL).

PMID- 7568446
TI  - Strange-male-induced pregnancy disruption in mice: reduction of vulnerability by
      17 beta-estradiol antibodies.
AB  - It is well-established that novel males can disrupt early pregnancy in house
      mice. Inseminated female C57BL mice were either left undisturbed or each exposed
      indirectly to a novel HS male through a wire-mesh grid during days 1-6 of
      pregnancy. Varied dosages of antibodies to 17 beta-estradiol were administered to
      females exposed to males. Vehicle-treated females exposed to novel males showed
      fewer litters than did nonexposed controls. Male-exposed females given 1 ml daily
      of the antibody showed rates of pregnancy comparable to those observed in
      controls. These data suggest that estrogen levels might play a role in strange
      male-induced pregnancy disruptions, converging with evidence implicating
      estrogens in stress-induced pregnancy blocks.

PMID- 7568447
TI  - Strange-male-induced pregnancy disruption in mice: potentiation by administration
      of 17 beta-estradiol to castrated males.
AB  - Previous evidence suggests that androgen activity is necessary for strange males
      to disrupt early pregnancy in mice. Inseminated females were housed below
      castrated males, separated by a wire-mesh grid. Castrated males did not disrupt
      pregnancy, whereas those given daily injections of 27 or 81 micrograms of 17 beta
      estradiol did so. In conjunction with previous evidence, these data suggest a
      similarity between the hormones involved in the capacity of males to disrupt
      pregnancy and the hormones directly implicated in the females' vulnerability to
      pregnancy disruption.

PMID- 7568449
TI  - We owe our patients the best in nursing care.

PMID- 7568448
TI  - A possible involvement of VIP in feeding-induced secretion of ACTH and
      corticosterone in the rat.
AB  - For decades it has been known that brain/gut peptides are released during the
      ingestion of a meal. Although a multitude of actions have been attributed to
      these peptides acting in the brain, including the release or inhibition of a
      variety of pituitary hormones, the actual physiological roles of these substances
      in the brain have not been confirmed. For the first time, we have demonstrated
      that feeding-induced hypothalamic-pituitary-adrenal (HPA) secretion may involve
      the brain/gut peptide, vasoactive intestinal peptide (VIP), acting in the
      paraventricular nucleus (PVN) of the hypothalamus. The effects of 24 h fasting
      and refeeding on the release of plasma ACTH and CORT secretion in male rats were
      investigated. Blood samples were collected 5 min prior to PVN administration of
      saline or VIP antagonist, [Lsy, Pro, Arg, Tyr]-VIP and 30 min after refeeding.
      Plasma ACTH and CORT concentrations were significantly increased by 43 and 485%,
      respectively, by 30 min ingestion of food. Pretreatment with the VIP antagonist
      (0.75 and 1.5 nmol/rat) significantly reduced the food-induced ACTH response by
      69 and 76% and the CORT response by 58 and 65%, respectively. There were no
      significant differences in food-intake among groups. These results suggest that
      one potential role of hypothalamic VIP may involve activation of hypothalamic
      releasing factors to regulate ACTH and CORT levels during or after a meal.

PMID- 7568450
TI  - President's message: spiritual support: care of the whole person.

PMID- 7568451
TI  - Psychological dimensions of aesthetic surgery: essentials for nurses.
AB  - With the many technical advancements and increasing frequency of aesthetic
      surgery, plastic surgical nursing practice is expanding rapidly. Understanding
      the psychological motivations, profiles, and perioperative expectations of
      aesthetic surgery patients is essential in helping nurses prepare individuals for
      optimal perioperative experiences and outcomes.

PMID- 7568452
TI  - Endoscopic techniques in aesthetic plastic surgery.
AB  - There has been an explosive interest in endoscopic techniques by plastic surgeons
      over the past two years. Procedures such as facial rejuvenation, breast
      augmentation and abdominoplasty are being performed with endoscopic assistance.
      Endoscopic operations require a complex setup with components such as video
      camera, light sources, cables and hard instruments. The Hopkins Rod Lens system
      consists of optical fibers for illumination, an objective lens, an image
      retrieval system, a series of rods and lenses, and an eyepiece for image
      collection. Good illumination of the body cavity is essential for endoscopic
      procedures. Placement of the video camera on the eyepiece of the endoscope gives
      a clear, brightly illuminated large image on the monitor. The video monitor
      provides the surgical team with the endoscopic image. It is important to become
      familiar with the equipment before actually doing cases. Several options exist
      for staff education. In the operating room the endoscopic cart needs to be
      positioned to allow a clear unrestricted view of the video monitor by the surgeon
      and the operating team. Fogging of the endoscope may be prevented during
      induction by using FREDD (a fog reduction/elimination device) or a warm bath. The
      camera needs to be white balanced. During the procedure, the nurse monitors the
      level of dissection and assesses for clogging of the suction.

PMID- 7568453
TI  - Application of endoscopic techniques in aesthetic plastic surgery.
AB  - Although plastic surgeons had been slow to incorporate endoscopic techniques into
      their surgical armamentarium, there has been considerable interest in this field
      during the last 2 years. The aim of endoscopic brow lifting has been to achieve
      elevation of the brow through small scalp incisions without the associated nerve
      damage of the open approach and to accurately address excision of the muscles
      responsible for frowning. Endoscopic neck lift is a more recently pioneered
      technique which, although still in developmental stages, appears to provide good
      results. The technique involves undermining the skin of the neck extending from
      the chain to the jawline around the ear. Endoscopic facelifting is still very
      much in the experimental stages. Endoscopic techniques reduce the need for an
      incision in front of the ears. Using the endoscope, it has become a simple matter
      to perform a transaxillary breast augmentation using very small axillary
      incisions and precise placement of the implants. This results in excellent
      symmetry postoperatively and easy scar concealment. Abdominoplasty is another
      example of a procedure usually associated with a long incision and some degree of
      postoperative pain and immobility. Endoscopic abdominoplasty has been devised to
      provide not only contouring of abdominal fat through liposuction, but correction
      of the weakened abdominal muscle through a small incision placed just above the
      suprapubic hairline.

PMID- 7568454
TI  - Taking the O.R. to the office. Prevention and early detection of postsurgical
      hematomas.

PMID- 7568456
TI  - Skin care, chemical face peeling, and skin rejuvenation.
AB  - Chemical face peeling is the application of solutions to the face to lift off
      various layers of the skin and remove wrinkles. Three types of chemical peels are
      currently available. Alpha hydroxy acid (AHA) peels are the most mild and, in
      lower concentrations, can be applied by nurses. Trichloracetic acid (TCA) peels
      are designed for peels of medium depth. Phenol peels are the oldest form of
      chemical peels and are used to remove deeper wrinkles. Skin care, including sun
      block, is important to the success of all three types of peel.

PMID- 7568455
TI  - Women and saline breast implant surgery.
AB  - Since clinical studies are ongoing relative to breast implants, keeping up with
      the most current information is an important aspect of nursing practice. This
      article will provide answers to five basic questions that arise in regards to
      breast implantation and nurses' roles in the process.

PMID- 7568457
TI  - The Nordstrom's of medical practices.
AB  - While managed care has been touted as potentially putting an end to the private
      practice of medicine, the area of elective surgery is in a position to thrive.
      Plastic surgery practices and surgicenters are ideally positioned to provide
      superior patient care, providing a smart blend of old-fashioned service and state
      of-the-art surgical care. Coupled with a current interest in facility
      accreditation, private practices and surgicenters are poised to enjoy a bright
      future.

PMID- 7568459
TI  - Aesthetic rhinoplasty.

PMID- 7568458
TI  - A research critique: the impact of the media on women with breast implants.

PMID- 7568460
TI  - The nurse's role and responsibilities regarding patient satisfaction.

PMID- 7568462
TI  - Patient education materials for augmentation mammoplasty patients.

PMID- 7568461
TI  - Cash--just another four-letter word?

PMID- 7568463
TI  - Mobilization of Bacillus thuringiensis plasmid pTX14-3.
AB  - The Bacillus thuringiensis subsp. israelensis (Bti) plasmid pTX14-3 has been
      reported to contain a gene, mob14-3, with considerable homology to genes encoding
      mobilization proteins from other gram-positive bacteria. We have used the
      aggregation-mediated conjugation system recently discovered in Bti to compare the
      mobilization kinetics of different derivatives of plasmid pTX14-3. Plasmid pTX14
      3 has been found to replicate by the rolling-circle mechanism and to contain a
      locus suppressing the formation of high-molecular-weight DNA. We found that
      deleting a DNA fragment containing this locus increased the transfer frequency
      about twofold. The mobilization frequency of the plasmid containing the intact
      mob14-3 gene did not indicate a mobilization-enhancing activity of the encoded
      polypeptide. However, the presence of the mob14-3 gene seemed to increase the
      stability of the plasmid in exponential growth.

PMID- 7568464
TI  - The erythromycin resistance gene of the Corynebacterium xerosis R-plasmid pTP10
      also carrying chloramphenicol, kanamycin, and tetracycline resistances is capable
      of transposition in Corynebacterium glutamicum.
AB  - The clinical isolate Corynebacterium xerosis M82B carries the 50-kb R-plasmid
      pTP10 that confers resistance to the antibiotics chloramphenicol, kanamycin,
      erythromycin, and tetracycline. A detailed restriction map of pTP10 was
      constructed by cloning and analyzing restriction fragments of pTP10 in
      Escherichia coli. The resistance determinants of pTP10 were located by studying
      the phenotype of the recombinant plasmids in E. coli and Corynebacterium
      glutamicum. Restriction patterns of fragments encoding the kanamycin and
      erythromycin resistances revealed striking similarity to the kanamycin resistance
      of transposon Tn903 and the erythromycin resistance on plasmid pNG2 from
      Corynebacterium diphtheriae, respectively. Expression of the resistance
      determinants in E. coli and C. glutamicum ATCC 13032 led to high resistance
      levels in both strains, with the exception of the tetracycline resistance gene,
      which could be expressed only in C. glutamicum. Furthermore, the erythromycin
      resistance gene was found to be located on a transposable element which is
      functional in C. glutamicum strains.

PMID- 7568465
TI  - Iron transport genes of the pJM1-mediated iron uptake system of Vibrio
      anguillarum are included in a transposonlike structure.
AB  - The pJM1 genes encoding the proteins involved in iron transport in the
      anguibactin iron uptake system were found to be flanked by insertion sequences in
      a composite transposonlike structure. These Vibrio anguillarum insertion
      sequences, ISV-A1 and ISV-A2, are related to IS903, IS102, and the ISVs found in
      Vibrio parahaemoliticus, Vibrio mimicus, and non-O1 Vibrio cholerae flanking
      various tdh (thermostable direct hemolysin) genes. The inverted repeats at the
      ends of ISV-A1 and ISV-A2 have no more than three mismatches when compared to the
      inverted repeats of the other ISVs or IS903 and IS102. ISV-A1 and ISV-A2 are
      flanked by 9-bp direct repeats, which is the number of bases that are duplicated
      upon IS903 or IS102 transposition. The similarities found between the V.
      anguillarum ISVs and the other ISVs as well as IS903 and IS102 suggest that they
      derive from a common ancestral insertion sequence. At the end of ISV-A1 there is
      a -35 sequence region followed by a -10 sequence found in the pJM1 sequence
      immediately outside the ISV. This promoter region is followed by an open reading
      frame with the potential to encode a polypeptide of 26,985 Da whose function is
      still unknown. The functionality of this promoter has been demonstrated and
      expression analysis showed that the promoter is regulated by the iron
      concentration of the media.

PMID- 7568466
TI  - Sequences essential for replication of plasmid pIJ101 in Streptomyces lividans.
AB  - A 2.1-kb SacII DNA fragment of the high-copy-number Streptomyces lividans plasmid
      pIJ101 previously has been shown to include the functions required for
      maintenance of pIJ101 as an extrachromosomal replicon. This fragment contains the
      open translational reading frames rep and orf 56 plus an intervening segment
      believed to be noncoding. Using deletion mutations, we show that the pIJ101
      replication origin and other cis-acting sites necessary and sufficient for
      replication map to a DNA segment that extends 515 bp 5' to the translational
      start of Rep and lacks orf56. Plasmids that include this segment are maintained
      in S. lividans as extrachromosomal replicons when complemented in trans by the
      rep gene product.

PMID- 7568467
TI  - An episomal expression vector system for monitoring sequence-specific effects on
      mRNA stability in human cell lines.
AB  - A plasmid expression system has been developed which allows sequence-specific
      effects on mRNA degradation rates to be determined. This system uses stable,
      nonintegrating vectors that provide consistent levels of mRNA expression without
      the position effects common to integrating vectors. cDNAs encoding putative
      instability elements may be subcloned into the 5' untranslated region (5'UTR),
      the coding region, or the proximal 3'UTR of a beta-globin cDNA reporter. The
      effects of these sequences on mRNA stability may then be determined by
      actinomycin time course analyses of the fusion mRNAs and recombinant beta-globin
      mRNA in human cell lines. To demonstrate the utility of the vector system we
      fused an 820-bp fragment of the cDNA encoding the proximal 3'UTR of human 3
      hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase to the 3'UTR of the beta
      globin reporter and introduced the vector into the human hepatocarcinoma cell
      line, HepG2. The fusion mRNA was degraded at a rate 2- to 2.5-fold greater than
      that of beta-globin alone, at a rate similar to that reported for HMG CoA
      reductase mRNA in normal rat liver. Similar to a number of other relatively
      unstable mRNAs, the rate of fusion mRNA degradation was greatly decreased by
      treatment with cycloheximide.

PMID- 7568468
TI  - Plasmid pRTL1 controlling 1-chloroalkane degradation by Rhodococcus rhodochrous
      NCIMB13064.
AB  - Rhodococcus rhodochrous NCIMB13064 can dehalogenate and use a wide range of 1
      haloalkanes as sole carbon and energy source. The 1-chloroalkane degradation
      phenotype may be lost by cells spontaneously or after treatment with Mitomycin C.
      Two laboratory derivatives of the original strain exhibited differing degrees of
      stability of the chloroalkane degradation marker. Plasmids of approximately 100
      kbp (pRTL1) and 80 kbp (pRTL2) have been found in R. rhodochrous NCIMB13064.
      pRTL1 was shown to be carrying at least some genes for the dehalogenation of 1
      chloroalkanes with short chain lengths (C3 to C9). However, no connection was
      found between the utilization of 1-chloroalkanes with longer chain lengths (C12
      to C18) and the presence of pRTL1. Three separate events were observed to lead to
      the inability of NCIMB13064 to dehalogenate the short-chain 1-chloroalkanes; the
      complete loss of pRTL1, the integration of pRTL1 into the chromosome, or the
      deletion of a 20-kbp fragment in pRTL1. High-frequency transfer of the 1
      chloroalkane degradation marker associated with pRTL1 has been demonstrated in
      bacterial crosses between different derivatives of R. rhodochrous NCIMB13064.

PMID- 7568469
TI  - Novel insertion sequence-like element IS982 in lactococci.
AB  - A novel insertion sequence-like (IS) element, designated IS982, was found on the
      lactose plasmid, pSK11L, from Lactococcus lactis subsp. cremoris SK11 and was
      located between the origin of replication and the oligopeptide transport gene
      cluster. The 1003-base pair (bp) IS982 was flanked by 18-bp perfect inverted
      repeats. IS982 contained an open reading frame encoding a putative transposase of
      296 amino acids. An almost identical IS-like element (99% DNA sequence identity)
      was cloned and partially sequenced from the chromosome of Lactococcus lactis
      subsp. cremoris Wg2 with 17-bp perfect inverted repeats. Southern analysis
      indicated that in 12 lactococcal strains examined, IS982 was present with copy
      numbers ranging from 1 to at least 20. IS982 displayed sequence homology to the
      putative IS element RSBst-alpha from Bacillus stearothermophilus CU21, IS982 and
      RSBst-alpha were not related to other known insertion sequences and may represent
      a new family of IS elements.

PMID- 7568470
TI  - Construction and properties of cloning vectors based on a 7.2-kb Rhizobium
      meliloti cryptic plasmid.
AB  - Cloning vectors (pFD1001, pFD1192, pFD1194, and pFD1212) were constructed by
      extension of the host range of a 7.2-kb Rhizobium meliloti cryptic plasmid
      (pRM1132f) with the ColE1-based plasmids, pBR322, pACYC177, pACYC 184, pSUP301,
      or pHC179; mobilization was facilitated by introduction of the oriT region from
      pRK2, a broad-host-range plasmid. The vector plasmids transferred readily into a
      wide range of gram-negative bacteria and had relatively low copy number in R.
      meliloti; two constructs, pFD1001 and pFD1212, were completely stable in R.
      meliloti isolated from nodules of alfalfa (Medicago sativa). A representative of
      the vector constructs (pFD1001) could be maintained in R. meliloti in the
      presence of the broad-host-range shuttle plasmid pRK290. These two vector
      plasmids could be introduced into R. meliloti, either simultaneously or singly
      when pRK290 was the resident plasmid; however, entry of pRK290 was blocked when
      pFD1001 was the resident plasmid. The cloning vectors constructed in this study
      should prove to be useful for the genetic manipulation of Rhizobium.

PMID- 7568471
TI  - Replication enhancer requirement for recognition of heterologous replication
      origin by an initiator protein.
AB  - In the pT181 plasmid family, the replication initiation protein (Rep) encoded by
      each plasmid recognizes only its cognate origin, unless the Rep protein is
      expressed at abnormally high levels. Heterologous recognition of the origin of
      the pC221 plasmid by the RepC protein of the pT181 plasmid requires that cmp, the
      pT181 replication enhancer, be present on the same plasmid as the origin of
      replication. These findings indicate that cmp has a role in the specificity of
      Rep-ori recognition and support the model that cmp facilitates the
      formation/stabilization of the RepC-origin complex.

PMID- 7568473
TI  - Fetal reconstructive surgery: experimental use of the latissimus dorsi flap to
      correct myelomeningocele in utero.
AB  - A recent study in human fetuses with myelomeningocele produced evidence that
      nonclosure of the spine leads to progressive damage of the exposed spinal cord
      during pregnancy. Thus in utero coverage might spare function. We tested the use
      of the latissimus dorsi flap for fetal myelomeningocele repair. In seven sheep
      fetuses, a lumbar myelomeningocele type of lesion was created at 75 days'
      gestation and was covered with a "reversed" latissimus dorsi flap at 100 days. At
      term, the three survivors had healed cutaneous wounds and normal hindlimb
      function. The vascular pedicle of the latissimus dorsi flap was patent, the
      viable flap covered the entire lesion, and the underlying spinal cord was grossly
      intact. We conclude that the latissimus dorsi flap repair is suitable for fetal
      surgery and provides efficient coverage of the lesion. These results have
      clinical implications, since fetal myelomeningocele repair may be a compelling
      way to reduce the severe neurologic deficit in humans.

PMID- 7568474
TI  - Correction of scaphocephaly secondary to ventricular shunting procedures.
AB  - Craniosynostosis following ventricular shunting procedures for hydrocephalus has
      become a recognized complication of shunting procedures. Secondary synostosis
      results from a decrease in intracranial volume leading to collapse of the cranial
      vault. Since this represents a distinct etiopathogenesis different from that
      typically involved, the surgical approach should be altered. Eight patients with
      secondary scaphocephaly underwent surgical reconstruction. The clinical data and
      radiographic studies were reviewed for these patients. The surgical approach
      consisted of sagittal or parasagittal strip craniectomies, lateral osteotomies
      with bone-flap expansion, occipital and frontal remodeling as needed, and the
      application of rigid fixation to maintain contour and prevent recurrent collapse
      of the cranial vault. Patient follow-up ranged from 3 to 37 months. Five of these
      patients were premature infants, an association not previously recognized in the
      literature. Satisfactory results were obtained in all patients. Keeping the
      craniectomy sites parent and achieving a more normal cranial contour through
      cranial remodeling have provided good results in this population.

PMID- 7568472
TI  - Isolation and characterization of host mutants defective in msDNA synthesis: role
      of ribonuclease H in msDNA synthesis.
AB  - In some Escherichia coli strains, a single-stranded DNA (msDNA) covalently linked
      to RNA is produced by a reverse transcriptase (RT) encoded by a genetic element
      called a retron. We have looked for host genes involved in msDNA synthesis. From
      screening of 10,000 mutants generated by Tn5 insertions, we obtained 3
      chromosomal mutants defective msDNA synthesis. Analysis showed that all 3 mutants
      were affected in the gene for ribonuclease H (rnh). In rnh mutants, the reverse
      transcription products were heterogeneous with several sizes, smaller and bigger
      than the wild-type msDNA, showing that the reverse transcription is inhibited by
      the lack of RNase H activity. It also suggests that the RT recognizes the
      structure of msDNA for the termination of reverse transcription.

PMID- 7568475
TI  - Integrated life-sized solid model of bone and soft tissue: application for cleft
      lip and palate infants.
AB  - The recent development of three-dimensional computed tomography (3D-CT) and laser
      stereolithography has allowed the creation of life-sized skeletal models. The
      development of helical CT has enabled us to apply this method to very young
      children. However, skeletal models alone do not reveal the spatial relationship
      between soft tissue and bone in complicated craniofacial deformities. We have
      therefore developed a model that shows both soft and bony tissue by first using
      CT values that result in a model in which soft tissue is solid and bone is
      replaced by empty space. The space is then filled with plaster to represent the
      skeleton. This model also can provide baseline data for evaluating facial growth
      after surgical repair of clefts. Two infants with cleft lip and palate are
      presented to illustrate this method of creating an integrated solid model and its
      applications.

PMID- 7568476
TI  - The arterial basis of pharyngeal flaps.
AB  - The arterial basis of pharyngeal flaps is unknown. Injection and dissection
      studies have been used in 41 adult human cadavers to study the arterial supply of
      pharyngoplasties in current use. Superiorly based posterior pharyngeal flaps are
      "random" in nature, inferiorly based posterior pharyngeal flaps may include an
      "axial" vessel, laterally based posterior pharyngeal flaps will include an
      "axial" vessel, and laterally based "sphincter" pharyngoplasties, although
      supplied segmentally, will contain an "axial" vessel if raised up to but not
      beyond the upper pole of the tonsil.

PMID- 7568477
TI  - The arterial supply of the palate: implications for closure of cleft palates.
AB  - Little is known of the arterial anatomy of the palate. Injection studies and
      dissection of a total of 49 cadavers have shown the principal arterial supply of
      the soft palate to be the ascending pharyngeal artery, which anastomoses with the
      greater palatine artery at the junction of the hard and soft palates. The
      position and relations of the branches of the ascending palatine artery put it at
      risk during palate repair.

PMID- 7568478
TI  - Total reconstruction of the alar cartilage en bloc using the ear cartilage: a
      study in cadavers.
AB  - To determine whether the lamina tragi, isthmus, and cavum conchae are a donor
      area for reconstruction of the alar cartilage with all its elements (medial crus,
      junction of the medial and lateral crura, and lateral crus), with the same
      dimension and en bloc, 40 alar cartilages and 40 lower parts of ear cartilages of
      20 cadavers were dissected. Several measurements were taken in the alar
      cartilages, such as distance, thickness, and angle. Then they were compared with
      the measurements performed in the ear cartilages and segments removed from the
      lamina tragi, isthmus, and cavum conchae. This study, done with cadavers, shows
      that from the lamina tragi, isthmus, and cavum conchae, en bloc resection is
      possible with characteristics of form and dimension similar to those of the
      homolateral alar cartilage. The segment removed en bloc from the intermediate
      part of the lamina tragi, isthmus, and cavum conchae replaces, respectively, the
      medial crus, junction of the medial and lateral crura, and lateral crus.

PMID- 7568479
TI  - Transconjunctival versus transcutaneous lower eyelid blepharoplasty: a
      prospective study.
AB  - Debate continues over the relative merits of transconjunctival and the more
      customary subciliary transcutaneous approaches for lower lid blepharoplasty. Ten
      consecutive patients presented for blepharoplasty, and in all patients the
      transcutaneous subciliary musculocutaneous flap approach was used on the left
      lower eyelid and the transconjunctival preseptal approach was used on the right.
      Patients served as their own controls. Follow-up was evaluated clinically by
      patient questionnaire and by standardized photographs preoperatively and at 5
      days, 1 month, 3 months, and 6 months postoperatively. Photographs were graded
      independently by four blinded examiners. No statistical difference was identified
      in measured fornix depth between preoperative patients and postoperatively on
      each side. Average fat removed from each side was the same, and no patient had an
      identified "missed fat compartment." Three patients had mild bilateral scleral
      show postoperatively, and a fourth developed it on the left (transcutaneous)
      side. However, overall grading on both sides was universally very good with no
      significant difference on the two sides--0.68 on the right and 0.60 on the left
      (maximum worst grade could be 5.0 and best grade 0). The potential for external
      scarring was never a perceived problem in the transcutaneous technique.

PMID- 7568480
TI  - Correction of saddlebag deformity of the lower eyelids by superficial suction
      lipectomy.
AB  - A simple, quick, and safe method for the correction of eyelid saddlebag deformity
      is presented. Past techniques involved intricate muscle transposition flaps and
      extensive dissection. Anatomic dissection clearly demonstrates that the saddlebag
      deformity is caused by an excess of subcutaneous fat in a well-defined space
      similar to the fat pads of the upper and lower eyelids. This newly described fat
      pad lies over the preorbital fibers of the orbicularis oculi muscle and at times
      extends into the malar area. The technique of superficial suction lipectomy for
      the removal of eyelid saddlebag deformity is simple and done with local
      anesthesia on an outpatient basis. Results in multiple patients with follow-up
      ranging from 1 to 7 years are presented.

PMID- 7568481
TI  - A comparison of sedation techniques for outpatient rhinoplasty: midazolam versus
      midazolam plus ketamine.
AB  - A total of 859 patients presenting for outpatient rhinoplasty were divided into
      two groups that received intravenous sedation of midazolam 0.1 mg/kg either with
      or without ketamine 0.4 to 0.5 mg/kg immediately prior to conduct of the local
      anesthetic injections and surgery. Additional midazolam was given
      intraoperatively as needed. No patient received narcotic either as premedication
      or intraoperatively. Patients were evaluated by the surgeon on their response to
      the injections and surgery, and patients were given a questionnaire 1 week
      postoperatively to examine their response to and recall of the procedure. Scoring
      by both the surgeon and patients revealed that the great majority of patients in
      both groups had adequate "sedation." Patients from both groups related a high
      degree of satisfaction (> 90 percent) with the technique of sedation. The
      differences between the two study groups achieved statistical significance only
      on 4 of the 12 parameters investigated. Those who had received only midazolam
      were less likely to vocalize during the surgery or to experience the procedure as
      being of undue duration. Those who had also received ketamine had a lesser chance
      of remembering the local anesthetic injections (11.1 versus 19.8 percent) and a
      lesser likelihood of being dissatisfied with their surgical experience (3.3
      versus 7.4 percent). In conclusion, the use of an opioid-free sedative technique
      of intravenous midazolam was highly successful in meeting the needs of both
      patients and surgeons. The addition of a single preblock dose of intravenous
      ketamine to intravenous midazolam sedation for rhinoplasty does not improve
      intraoperative conditions for the surgeon in terms of patient behavior.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7568482
TI  - Use of distortions in the treatment of skin lesions of the face: the distorting
      excision.
AB  - Reconstruction after excision of a cutaneous lesion of the face is done by
      various complex old and new flaps to avoid any distortion. The distortions
      following primary closure of defects in the face are given undue importance. We
      have observed and used the capacity of self-correction of these distortions,
      which is partially due to the muscular actions. We show our experience in various
      distorting reconstructions of the face in 36 patients. Because of our partial
      presence in a children's hospital, most of our patients were children.

PMID- 7568483
TI  - Reconstruction of the base of the tongue with the microvascular ulnar forearm
      flap: a functional assessment.
AB  - Ten patients with infiltrating carcinomas of the base of the tongue/tonsillar
      region underwent 30 to 100 percent resection of the base of the tongue and
      lateral pharyngeal wall. The surgical defect was reconstructed (9 primary, 1
      secondary) with a large microvascular ulnar forearm flap that was selectively
      contoured to provide bulk for the base of the tongue and a thin lining for the
      pharyngeal wall. Seven patients were evaluated for swallowing and speech 6 weeks
      to 2 years following the reconstruction. Cineradiographic studies showed
      excellent base of the tongue and flap mobility allowing glossopharyngeal closure
      in all patients and complete pharyngeal evacuation in four patients. Four
      patients who were in good health preoperatively were able to eat a regular diet
      postoperatively, and the remaining three patients were able to handle soft food.
      Functional recovery after major tongue base surgery is contingent upon a three
      dimensional microvascular reconstruction using a thin forearm flap.

PMID- 7568485
TI  - A finite-element facial model for simulating plastic surgery.
AB  - CAPS (Computer-Aided Plastic Surgery) is a prototype computer program that uses a
      three-dimensional graphic model of a human face and incorporates a finite-element
      mathematical model of the physical properties of the soft tissue. This program
      can estimate the biomechanic consequences of ablation and rearrangement of
      tissue. The results of two hypothetical surgeries on the face are presented: A
      surgeon could use this program as a sketch pad to predict and compare the outcome
      of facial plastic procedures on a patient-specific model. The relation of this
      program to previous work is discussed, and directions for research and possible
      applications are addressed.

PMID- 7568486
TI  - Reduction mammaplasty: long-term efficacy, morbidity, and patient satisfaction.
AB  - This retrospective study was designed to determine if reduction mammaplasty
      relieved preoperative symptoms in patients with macromastia. Seven-hundred and
      eighty women who had reduction mammaplasties between 1981 and 1992 were surveyed.
      Responses to questions concerning the preoperative and postoperative symptoms,
      breast size, complications, and satisfaction were elicited. Completed surveys
      were returned by 406 patients (52 percent) who had bilateral operations. The mean
      age at surgery was 38 years, with an average follow-up of 4.7 years. Preoperative
      complaints of shoulder grooving (94 percent), shoulder pains (93 percent), and
      back pains (81 percent) were significantly reduced following surgery (McNemar
      test, p < 0.0001). Cup size decreased an average of two sizes in 72 percent.
      There were 215 women (53 percent) with postoperative complications, and although
      most were minor, 20 (5 percent) required surgical correction. Self-esteem
      improved in 358 (88 percent), and most would have surgery again (93 percent) and
      would encourage others to have the same (94 percent). Reduction mammaplasty
      decreases breast size and significantly relieves preoperative symptoms associated
      with mammary hypertrophy. Relief of symptoms was the most common reason women
      gave for having the operation, and 87 percent were satisfied with the results
      despite frequent minor postoperative complications.

PMID- 7568484
TI  - Free colon transfer for resurfacing large oral cavity defects.
AB  - Ideal reconstruction of the oral cavity includes a durable lining that is thin,
      supple, and innervated, and that provides a lubricated surface that facilitates
      deglutition and speech. This paper describes the use of free colon transfer for
      relining the oral cavity. In three patients, segments of transverse colon, split
      along the antimesenteric border, were transferred as free flaps on the middle
      colic vessels for large defects involving the alveolar ridge, buccal mucosa,
      floor of the mouth, tongue, and pharyngeal walls. All flaps were transferred
      successfully without adverse vascular events, abdominal complications, or oro
      cutaneous fistulas. One flap was re-elevated 2 weeks postoperatively for
      additional mandibulectomy. Two patients received postoperative radiation therapy
      and another patient received planned preoperative radiotherapy. The mucosal
      surface of the colon flattens to provide a thin, smooth, supple oral lining that
      produces moderate mucus, coapts well to the convoluted surfaces of the defects,
      and is durable to mastication and denture wear. Mucosal biopsy 2 years
      postoperatively in the nonradiated flap reveals normal colon mucosa with abundant
      mucin-producing cells. Free colon transfer is a "functional" reconstruction of
      the oral lining. The donor tissue is abundant and capable of resurfacing large,
      convoluted oral cavity surfaces with a thin, supple, mucus-secreting tissue that
      allows unimpaired tongue mobility, swallowing, speech, and denture wear.
      Furthermore, the presence of nonirradiated, mucus-secreting cells provides an
      avenue to further augment mucin production by topical and systemic agents.

PMID- 7568488
TI  - Classification of capsular contracture after prosthetic breast reconstruction.
AB  - The Baker classification of capsular contracture remains the most popular and
      practical method of assessing clinical firmness of the breast after augmentation
      mammaplasty. This classification system was never intended to describe prosthetic
      breast reconstruction. A modification of the Baker classification to include
      classes IA, IB, II, III, and IV has been developed to describe breast
      reconstruction more accurately. For this modified system, a soft but visible
      implant (class IB), an implant with mild firmness (class II), and an implant with
      moderate firmness (class III) could still be considered good or excellent
      outcomes. Only a class IV classification with an excessively firm and symptomatic
      breast resulting in a poor aesthetic result would necessarily be considered a
      poor outcome.

PMID- 7568487
TI  - Reconstruction and the radiated breast: is there a role for implants?
AB  - The use of breast implants in irradiated patients is controversial. Recently, 39
      irradiated implants were compared with 338 nonirradiated implants in 297 patients
      between January of 1975 and October of 1994 at The University of Texas M. D.
      Anderson Cancer Center. Tissue expanders and follow-up time of less than 6 months
      excluded patients from the study. Five groups of patients were identified. Group
      1 consisted of 7 patients and 7 implants who received postoperative adjuvant
      radiotherapy after implant placement. Group 2 consisted of 5 patients and 7
      implants who received preoperative adjuvant radiotherapy prior to implant
      placement. Groups 3 and 4 consisted of 2 and 12 patients (2 and 19 implants)
      placed beneath latissimus dorsi flaps who had postoperative and preoperative
      adjuvant radiotherapy, respectively. Group 5 contained 4 patients with 4 implants
      placed beneath a transverse rectus abdominis myocutaneous (TRAM) flap who had
      preoperative radiotherapy. All implants were placed submuscularly or beneath
      autogenous flaps. The average irradiated breast received 50 Gy. For statistical
      purposes, two categories were identified. Capsular contracture (Baker III or
      greater), pain, exposure, and implant removal in 6 of 14 implants that received
      radiotherapy were compared with similar complications in 33 of 266 implants
      without irradiation (p = 0.001). The second category contained 10 complications
      in 25 implants placed beneath autogenous reconstructions with radiotherapy
      compared with 6 of 72 similar complications in implants placed beneath autogenous
      reconstructions without radiotherapy (p = 0.000). Results showed that irradiation
      has significant negative effects on the reconstructive outcome with implants.
      Autogenous reconstruction did not appear to offer a protective role when placed
      over implants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568489
TI  - Clinical relevance of positive breast periprosthetic cultures without overt
      infection.
AB  - The true incidence of positive breast periprosthetic cultures in the absence of
      overt infection is not clearly established. We retrospectively reviewed data from
      389 implants that were removed for reasons other than clinical infection. Many of
      these patients presented with a variety of musculoskeletal ailments. Others had
      symptomatic capsular contracture as the presenting complaint. In a few a known
      implant rupture was the reason for explantation. We identified a positive culture
      rate of 23.5 percent from capsule tissue. Most of these organisms were coagulase
      negative staphylococci and anaerobic diphtheroids, but fungi and other organisms
      (generally felt to be more pathogenic than the less virulent coagulase-negative
      staphylococci) also were cultured. In an attempt to identify the clinical
      relevance of these positive cultures, we statistically evaluated the culture
      results for associations with capsular contracture, implant rupture, type of
      implant, and location of implant. Of these, the only statistically significant
      correlation was between positive culture result and symptomatic capsular
      contracture (Baker class IV).

PMID- 7568492
TI  - Salvage of traumatic below-knee amputation stumps utilizing the filet of foot
      free flap: critical evaluation of six cases.
AB  - Over a 12-year period between 1979 and 1991, 27 patients were operated on at the
      New York University Medical Center for salvage of below-knee amputation stumps
      utilizing free flaps. Six different donor sites were used. In 6 patients, the
      amputated foot was the donor site for a free flap to cover the tibial stump.
      There were 3 males and 3 females in this group. Five of the patients underwent
      immediate filet of foot reconstructions, while 1 patient had a reconstruction
      performed 69 days after injury, electively, when it was determined that below
      knee amputation was the best option. All foot flaps survived and ultimately
      provided the major soft-tissue coverage for the below-knee amputation stump. The
      length of hospitalization ranged from 24 to 118 days. The time required from foot
      filet procedure to ambulation was 2, 4, 6, 7, 9, and 12 months in the 6 patients.
      Five of the 6 patients have resumed work or school after their injury. Foot flaps
      were based on the posterior tibial artery, anterior tibial artery, or both
      vessels. Nerve anastomosis of the posterior tibial nerve was performed in 5
      patients. In 1 patient it was possible to maintain the continuity of the
      posterior tibial nerve. Five of the 6 patients were tested over a year after the
      flap, and all have good cold, pressure, and vibration sensation. Two of the 5
      patients have heat sensation, and all 5 patients have at least protective
      pressure sensation. All the patients ambulate well with a below-knee prosthesis.

PMID- 7568490
TI  - Functional soft-tissue coverage in skeletonizing injuries of the upper extremity
      using the ipsilateral latissimus dorsi myocutaneous flap.
AB  - The concept of early "functional" soft-tissue coverage is demonstrated in three
      cases of severe skeletonizing avulsion/contusion injuries of the upper extremity,
      including the replantation of a "frozen" arm. According to the MESS score, all
      extremities would have been allocated to the amputation group. Therapeutic
      strategy consisted of primary repair of all neurovascular structures, serial
      debridements, and early definitive coverage with simultaneous restoration of the
      elbow flexor or extensor muscles. Flap survival was 100 percent in all patients,
      and the muscle strength achieved after vigorous physical therapy was rated M3 to
      M5. One patient was even able to return to competitive tennis.

PMID- 7568491
TI  - Atherosclerosis of the lower extremity and free-tissue reconstruction for limb
      salvage.
AB  - Atherosclerosis of the lower extremity frequently leads to limb-threatening
      ischemic soft-tissue wounds. Over the past 44 months, 30 selected patients with
      arterial disease documented by angiography were treated with combined vascular
      reconstruction and free-tissue transfer for limb salvage. Soft-tissue defects
      occurred on the plantar and dorsal surfaces of the foot and distal tibia with
      significant bone, tendon, or joint exposure. Thirteen patients had osteomyelitis.
      Eighteen patients underwent simultaneous soft-tissue and vascular reconstruction,
      while 12 patients underwent delayed soft-tissue reconstruction. The free-flap
      tissues included the rectus abdominis flap in 13, the latissimus dorsi flap in 7,
      the radial forearm flap in 5, the scapular flap in 3, and the omentum flap in 2.
      Autogenous venous bypass was performed to the popliteal segment in 6 patients and
      the infrapopliteal arteries in 18. Five patients had inadequate outflow for
      complete vascular reconstruction and were treated with proximal vein grafts
      directed into the free flap. Twenty-two patients (73 percent) had successful free
      tissue transfer and bypass graft patency and were independent ambulators over the
      mean follow-up period of 22 months. Of the 8 unsuccessful reconstructions, 3
      patients had early free-flap and graft failure. Five patients developed new areas
      of ischemic disease despite graft and flap patency. All 8 patients were treated
      with amputation; 7 never regained ambulation. The combined application of
      vascular and free-flap soft-tissue reconstruction for the threatened ischemic
      lower extremity has produced excellent functional results in the majority of our
      patients.

PMID- 7568493
TI  - Lower limb salvage by microvascular free-tissue transfer in patients with
      homozygous sickle cell disease.
AB  - Chronic, excruciatingly painful ulcerations of the lower extremities in patients
      with homozygous sickle cell anemia (HbSS) present a frustrating clinical problem
      for the reconstructive surgeon. Despite adequate wound care and skin grafting,
      there is a dismally high incidence of recurrence. Furthermore, there is a paucity
      of reliable locoregional fasciocutaneous, muscle, and myocutaneous flaps in the
      ankle region. Free-tissue transfer has become the procedure of choice for
      reconstruction of the lower third of the leg. However, in sickle cell anemia,
      does the obligate period of flap ischemia inherent in free-tissue transfer
      inevitably doom a flap to failure? We present our multidisciplinary experience
      over 55 months with five free flaps in four homozygous sickle cell anemia
      patients 21 to 38 years old who had chronic nonhealing leg ulcerations. Special
      perioperative measures included exchange transfusion to lower hemoglobin S to
      below 30 percent, maintaining the hematocrit at 31 to 35 percent, intraoperative
      flap washout and perfusion with warm heparinized saline-dextran solution,
      administration of dextran and aspirin intraoperatively and postoperatively,
      prophylactic topical and systemic anti-Pseudomonas antibiotics, supplemental
      oxygen, and warm ambient room temperature. Flaps included the latissimus dorsi
      muscle (two patients), the temporoparietal fascia (one patient), and "split"
      omentum for bilateral lower limb salvage (one patient). Successful free-tissue
      transfer was accomplished in all patients. One patient suffered gradual partial
      occlusion of the microcirculation by sickled erythrocytes following a transient
      hypothermic, hypotensive episode. Sufficient flap tissue survived to permit skin
      grafting with an excellent result. Pseudomonas infection occurred in two patients
      (three flaps).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568494
TI  - Partial soleus muscle island flap transfer using minor pedicles from the
      posterior tibial vessels.
AB  - A new method for partial soleus muscle island flap transfer using minor pedicles
      from the posterior tibial vessels was designed and executed. A portion of the
      soleus muscle body that was slightly wider than the defect was harvested with
      minor pedicles. The muscle flap was transposed by turning it over or by creating
      an island flap. Skin grafts were applied to the exposed muscle. This new type of
      muscle flap was applied to six patients with a pretibial skin defect at the lower
      third of the leg. It was used for treatment of an open fracture with an
      associated skin defect in four patients, chronic osteomyelitis in one patient,
      and a recurrent stasis ulcer in one patient. In all patients the transferred
      muscle flap survived completely.

PMID- 7568495
TI  - In vitro model of syndactyly replicates the morphologic features observed in
      vivo.
AB  - Syndactyly is a common congenital hand anomaly that may occur after exposure to
      teratogens. We have developed an in vitro model of syndactyly to investigate the
      molecular mechanisms underlying this malformation of digit development. Retinoic
      acid, which regulates pattern formation in vertebrate limb development and is
      associated with teratogenic malformations, was used in the development of this
      syndactyly model system. Pregnant Swiss-Webster mice were given retinoic acid by
      oral gavage on days 10 and 11 of embryonic development (E10 and E11,
      respectively). The mice were sacrificed on gestational days 13 and 17 (E13, E17)
      and immediately postnatally (PN). The fetuses were removed and the forelimbs
      dissected under the operating microscope. The E13 limbs were cultured for 4 days
      (E13+4) in an organ culture system using a serumless, chemically defined medium.
      The E17, PN, and E13+4 forelimbs were critically examined for malformations of
      digit separation and digit development. Retinoic acid-induced fetal mouse
      forelimb syndactyly was observed in all the groups; 81 percent of E17 limbs, 75
      percent of PN limbs, and 77 percent of E13+4 limbs had syndactyly. The morphology
      of the digital malformations was similar in the E17, PN, and E13+4 limbs. This in
      vitro model permits further studies to characterize the molecular changes that
      occur during the development of a congenital hand anomaly.

PMID- 7568497
TI  - Thrombin promotion of isometric contraction in fibroblasts: its extracellular
      mechanism of action.
AB  - Isometric force generated by fibroblasts plays an essential role in tissue
      contraction during normal wound healing and pathologic contractures. Thrombin, a
      serine protease present in all wounds, has been shown to promote wound healing.
      The purpose of this study was to determine the extracellular mechanism by which
      thrombin promotes isometric contraction by fibroblasts in an in vitro collagen
      lattice model of tissue contraction. The amount of isometric force generated by
      human fibroblasts can be measured directly with a stabilized collagen lattice
      attached to a force transducer. Thrombin promoted isometric contraction by human
      fibroblasts in a dose-dependent manner. In addition, thrombin-promoted isometric
      contraction is dependent on the enzymatic and anionic binding activity of
      thrombin, as demonstrated by inhibition with specific enzymatic and anionic
      binding inhibitors. These results suggest that thrombin may promote isometric
      contraction by fibroblasts through the enzymatic cleavage of its cell surface
      receptor, resulting in a new amino terminus that serves as a "tethered ligand" to
      activate the receptor directly. To test this mechanism of action, a synthetic
      peptide (SFLLRN) representing the "tethered ligand" region of the activated
      thrombin receptor was synthesized and examined for its ability to promote
      isometric contraction by fibroblasts. This peptide promoted fibroblast
      contraction in a dose-dependent manner. In contrast, a control isomer peptide
      (FSLLRN), in which the two amino-terminal amino acids were reversed, failed to
      promote this response. These findings demonstrate that human alpha-thrombin
      promotes isometric contraction by human fibroblasts and that binding to and
      cleavage of its cell surface receptor are integral to this response.

PMID- 7568498
TI  - The plastic surgeon and the insurance review process.

PMID- 7568501
TI  - Free combined thin wrap-around flap with a second toe proximal interphalangeal
      joint transfer for reconstruction of the thumb.
AB  - The combined thin wrap-around flap from the big toe and the proximal
      interphalangeal joint of the second toe is characterized by (1) a single
      vascularized joint, which is used to preserve the second toe with a free iliac
      bone graft, (2) a thin wrap-around flap, which allows the pulpal fatty tissue on
      the remaining bone of the big toe to be retained and accept a skin graft, (3) a
      wrap-around flap with a partial distal phalangeal bone, and (4) a microplate for
      firm fixation at the proximal bone union and early joint motion. The advantages
      of this method are (1) the cosmetic appearance is excellent with use of the thin
      wrap-around flap; (2) there is joint motion in the reconstructed thumb with
      strong pinch and vice pinch; (3) the vascularized joint with a microplate allows
      for early postoperative motion; (4) bone grafting from another donor site is
      unnecessary; (5) bone growth is possible in children with open epiphyses; and (6)
      the big and second toes are preserved with minimal donor-site morbidity. This
      method is indicated for thumb losses at a level distal to the metacarpophalangeal
      joint or at the level of the proximal phalanx.

PMID- 7568499
TI  - The Plastikosians vs. the Parasiteans.

PMID- 7568500
TI  - Functional reconstruction of a bilateral maxillectomy defect using a fibula
      osteocutaneous flap with osseointegrated implants.
AB  - We have achieved functional reconstruction for a bilateral upper alveolar bone,
      gingival, and palatal defect that has various problems originating from
      instability of the prosthesis using the fibula osteocutaneous flap with
      osseointegrated implants. The flap had three bone segments and two skin paddles.
      The combined bone segments created the upper alveolar arch, and the skin paddles
      closed the palatal defect. Nine months later, prosthodontic treatment was
      performed successfully. Our procedure restored the patient to masticatory
      function of the upper jaw, intelligible speech, and natural facial appearance. As
      a result, quality of life of the patient was extremely improved.

PMID- 7568496
TI  - Preventing the infiltration of leukocytes by monoclonal antibody blocks the
      development of progressive ischemia in rat burns.
AB  - Tissue loss as a consequence of thermal trauma occurs in two stages. There is
      immediate necrosis in tissues directly killed by the thermal energy, followed by
      a delayed secondary necrosis in neighboring tissues. The infiltration of
      neutrophils into traumatized tissues is a hallmark of the inflammatory response.
      Neutrophils have the machinery to kill invading microorganisms, but these same
      weapons have the capacity to destroy the host's viable tissues as well. Leukocyte
      infiltration requires their adherence to the vascular endothelial cell surface.
      Masking these adhesion sites on neutrophils will block the adhesion of
      neutrophils to the endothelium. A monoclonal antibody (mAb) was developed to
      guinea pig leukocyte adhesion sites CD11b/ CD18, and this mAb cross-reacts with
      rat leukocytes, blocking their adherence. Rats received a "comb burn" composed of
      four rectangular full-thickness burns placed in a row and separated by three
      areas left unburned. The four individual burns convert into a single large wound
      because the blood flow to the interspaces was terminated, blood vessels were
      occluded, and leukocytes were present in the extravascular space. The systemic
      administration of the mAb (50 to 150 microliters) immediately following a comb
      burn promoted the survival of the interspace, demonstrated by the prevention of
      loss of blood flow by laser Doppler monitoring, maintained patent vessels by
      latex vascular casts, blocked extravascular migration of neutrophils
      histologically at 2 hours, and limited the tissue loss to the original four
      burns.

PMID- 7568502
TI  - Retrograde dissection of the vascular pedicle in toe harvest.
AB  - A retrograde approach to dissection of the vascular pedicle in toe-to-hand
      transfer is presented, along with a simplified view of the vascular anatomy of
      the first web space. This approach has several advantages. First, the dominant
      vascular supply to the toe is elucidated early in the procedure, allowing for
      less unnecessary dissection of an inadequate pedicle. This also eliminates the
      need for preoperative arteriography. Furthermore, in cases where a lengthy
      pedicle is not required, retrograde dissection dispenses with harvest of a
      proximal vessel, which will not be needed for the transfer, and destructive
      dissection of the foot can be minimized.

PMID- 7568505
TI  - The silent observer.

PMID- 7568504
TI  - Prefabricated flaps: experimental and clinical review.
AB  - Prefabricated flaps are a useful tool for the reconstructive surgeon and present
      a number of advantages: 1. Specific preferred tissue composites, regardless of
      their native vascular origin, can be transferred as free or pedicled flaps. 2.
      Larger flaps of specialized tissue may be transferred safely. 3. Donor-site
      morbidity is reduced. 4. The functional outcome for the patients may be more
      satisfactory. The various methods of flap prefabrication include vascular
      induction through stage transfer; pretransfer delay, expansion, and grafting; the
      use of alloplastic materials; and tissue bioengineering. We have reviewed both
      the experimental and clinical research on flap prefabrication, describing the
      theory, technique, and advantages of each method.

PMID- 7568503
TI  - Intraoperative thrombolytic treatment of microarterial occlusion by selective rt
      PA infusion.
AB  - The development of microvascular thrombosis during replantation surgery or free
      flap transfer is generally best treated by identification of the problem,
      vascular revision, and reanastomosis. It is not unique, however, that surgical
      measures alone are insufficient or undesirable. Pharmacologic adjuncts are widely
      used for the prevention and sometimes treatment of microvascular thrombosis in
      surgical practice, but the benefit of thrombolytic agents, effective in
      dissolving an already established thrombus, is usually considered counterlevered
      by the fear of uncontrollable bleeding. However, selective infusion of the drug
      reduces the risk for systemic complications considerably and may therefore be
      considered in peripheral microvascular reconstruction. The technique was used
      successfully in a case of digital revascularization, where an arterial thrombosis
      was dissolved with the use of recombinant tissue plasminogen activator (rt-PA).

PMID- 7568508
TI  - The Fourth International Congress of Oriental Aesthetic Plastic Surgery.

PMID- 7568506
TI  - Understanding today's health care costs.

PMID- 7568507
TI  - Suturing oral mucosa under local anesthesia.

PMID- 7568509
TI  - Postoperative "bridge fixing method" in cleft lip surgery.

PMID- 7568510
TI  - Dynamic SMAS test.

PMID- 7568511
TI  - The efficacy of breast augmentation: breast size increase, patient satisfaction,
      and psychological effects.

PMID- 7568512
TI  - Thin Silastic sheet for orbital floor repair.

PMID- 7568513
TI  - [The deconstructions of schizophrenia (I)].
AB  - Standing in the midst of this great historical change, as sometimes it is called
      the switch to the "post-modern", we are now confronted with the demand of
      paradigm change in every field of scientific knowledge. So it is the case with
      psychiatry. Just about 100 years ago, the trend of "social defense" (society's
      need to be protected from harm) was going on covering the whole civilized
      countries. It brought about a situation that could be generalized as
      "institutionalism" which made mental hospitals huge and custodial, resulting in
      the prevalence of nihilism with regard to treatment. It was just at this time
      that Dementia praecox, the preconcept of Schizophrenia, was formed by Kraepelin,
      E. (1896) as a mental disease resulting in peculiar dementia. After some period,
      Dementia praecox was transformed into Schizophrenia (Gruppe der Schizophrenien)
      by Bleuler, E. (1908) with a new methodology: to grasp the disease from the
      symptomatic viewpoint. Jaspers, K. (1912) as well as Schneider, K. (1938)
      followed him in the way that was psychopathologically more strict; the latter
      reached the formulation of the <symptoms of 1st rank>. Despite this eventful
      metamorphosis of the concept of Schizophrenia, its fundamental traits have
      remained unchanged until the late 1960's. They could be summarized as follows: 1)
      What patients mention is incomprehensible; 2) The prognosis leads to peculiar
      dementia; 3) The real cause of the disease is the brain disorder. These three are
      the reflection of the custodialism, curative nihilism and materialism through the
      institutionalized mental hospitals in those days. Now, since the 1970's, the
      situation has been completely changed, or at least, faced with inevitable
      changes. The tide of "deinstitutionalization" is covering all over the civilized
      countries, demanding the normalization of mentally disordered persons. Thus,
      deprived of its motherland (i.e. institutionalism), the concept of Schizophrenia
      has got into confusion or even crisis. And in order to relieve this confusion,
      severe attempts are internationally being made to identify the diagnostic
      criteria of Schizophrenia by means of what they call "operational diagnosis". I
      believe, however, that what is truely necessary is not such a compromising
      modification, but a more radical change that is: the DECONSTRUCTION OF
      SCHIZOPHRENIA.

PMID- 7568515
TI  - [Diagnosis of Taijin-Kyofu and social phobia].

PMID- 7568514
TI  - [Integrated psychotherapy for eating disorders].
AB  - The various psychotherapeutic strategies for eating disorders (EDs) include
      psychoanalytic, cognitive-behavioral, family oriented, arts therapy and others.
      In this paper, the psychodynamism of EDs and their therapy are reexamined and
      considered holistically from "the separate aspects of eating" point of view. That
      is the separation of eating regulated by biological appetite and the eating or
      not eating deriving from the patient's mind, unrelated to appetite. A new
      therapeutic technique called "formalization", which clarifies the separation of
      aspects of eating are invented. For integrated psychotherapy of EDs, it is
      necessary to combine the formalization technique of which clarifies and promotes
      patients' conflicts, and the integrated psychodynamic therapies that treat the
      promoted conflicts. The psychodynamism of EDs is the subject of much argument by
      many therapist. Although these arguments differ, they are similar in two points.
      Firstly, all of them consider EDs as distinctly separate from biological
      appetites. Secondly, the behavior of patients with EDs are taken as "false
      solution" or "substitution" of their essential problem. It is impossible to
      completely separate the physical action of eating mentally, however there may be
      a second meaning of eating separate from appetite. Seen in this light,
      psychotherapies are classified into two groups. One supports and sympathizes with
      these conflicts and the other is an educational one, telling the patients that a
      false solution is invalid. The former approach is employed by almost all
      psychodynamic therapies, such as psychoanalysis, family oriented therapy, arts
      therapy, self-help groups and the like. These therapies treat patients' conflicts
      with a non-judgemental approach, transform the psychodynamism, and consequently
      improve the eating behavior. The latter is applied by behavior therapy. Under
      strict operant conditioning, adequate behavior is reinforced by reward and
      inadequate behavior is eliminated by punishment. This way aims to transform the
      behavior first, change the cognition, and turn off the conflicts. In this sense
      the eating behavior and its psychological meaning are rated by a fixed value
      system. It is therefore important to integrate the strong points of these
      therapies. In other words, the therapeutic approach must be effective in
      improving behavior, maintaining good therapeutic relationships, radically
      transforming their psychodynamism. Formalization is a process of clarification of
      the separate aspects of eating in cases of EDs. At the beginning of treatment it
      is essential to clarify the double meaning of symptoms. Psychodynamically, there
      must be a "good" meaning in ED and it is necessary to be appraised.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7568516
TI  - [The psyche, the immunological system and problems of health and disease].
AB  - Psychoneuroimmunology is a new tendency in the science, which integrates medicine
      and the social sciences. Interdisciplinary point of view on the etiology and the
      treatment of the many diseases fortifies the empirically holistic conception.
      Which is very old in medicine. The disease is the result of the collapse of the
      defensive mechanism in stress. The nervous, hormonal and immunological systems
      are integrated. The social environment and stress influence the individuals
      personality and cause diseases. The difficult situations, for instance: death of
      a close person divorce, examination, solitude etc., frequently cause
      immunosuppression. Psychotherapy can "wake" up the immune system.

PMID- 7568517
TI  - [Two decades of the concept of alexithymia].
AB  - In the early 1970's, American researchers Sifneos and Nemiah, using the results
      of there own studies and those of Ruesch, McLean, Marty and others, proposed an
      original concept of psychosomatic disorders, called the concept of alexithymia.
      It has become very popular in many research centres in the USA, Germany and
      Italy. The concept has been based upon the role of the so called alexithymic
      personality traits, which were found more often in patients with psychosomatic
      disorders than in other patient populations. Alexithymia (lack of words for
      emotions) has been defined as a set of psychological dispositions due to specific
      deficits in emotional and cognitive areas. Persons with alexithymic features
      present difficulties in perception and verbalization of emotions, cannot
      distinguish between vegetative feelings and emotions, and possess externalistic,
      outwardly directed cognitive style. Initially, alexithymia was linked to the
      etiology of psychosomatic disorders. Later, it was found in other pathological
      conditions such as somatization disorder, post-traumatic stress disorder, alcohol
      and substance abuse, neuroses and also in normal population. The origin of
      alexithymic features is seen as the dysfunction of limbic system, abnormal
      cerebral lateralization as well as disturbances in early learning of verbal and
      emotional associations. Alexithymic traits are also regarded as a specific
      homeostatic mechanism allowing for nearly normal functioning at expense of
      somatization. Twenty years after, the concept of alexithymia is still a focus of
      interest in many scientific centres. The most active is a Canadian research
      group, the authors of Toronto Alexithymia Scale, which is now considered the best
      measuring tool for alexithymia. Alexithymia has now been regarded a permanent
      personality trait and alexithymia theory can make a new psychosomatic paradigm.

PMID- 7568519
TI  - [Diagnosis and differential diagnosis of endogenous psychoses].
AB  - This paper describes development of concepts of diagnosis and differential
      diagnosis between endogenous psychoses: schizophrenia and depression. It explains
      the most important concepts of classification founded on different assumptions.
      Essential factors which influence diagnosis and differential diagnosis such as
      prognostic, psychopathology, drug response and anatomopathology were presented.
      Apart from concepts presuming exact differential diagnosis between schizophrenia
      and depression, more current resolution of the problem was presented:
      differential typology instead of differential diagnosis. The conclusion is that
      classification which closely relates diagnosis to clinical practice (treatment)
      is most valuable.

PMID- 7568518
TI  - [Schizophrenia: one or two psychoses? Positive and negative symptoms].
AB  - In this paper are presented conceptions of the twofold idea of schizophrenia as
      disease of two types dependent on positive or negative symptoms. Actual
      examination of fundamental research about the fluctuating of brain turnover of
      neurotransmitters confirm Crow's theory of selected two types of schizophrenic
      patients. In conclusion the results suggest that, depending on the course of
      schizophrenia, individual and multiplex forms of treatment including
      pharmacotherapy, psychotherapy and psychosocial effects are required.

PMID- 7568520
TI  - [The influence of infertility on women's personality].
AB  - The purpose of this investigation was to analyze several personality dimensions
      including several psychopathological symptoms of women experiencing infertility.
      70 females experiencing infertility and 50 healthy women were examined using
      psychological methods: MMPI and the State-Trait Anxiety Inventory by Spielberger,
      Gorsuch and Lushene. Personality profiles did not differ significantly for the
      two groups (remained within normal limits). In comparison with healthy women,
      women treated because of infertility displayed significantly higher level of
      anxiety as a state.

PMID- 7568521
TI  - [Case study of an anxious child].
AB  - Separation and individuation process ceases to be physiological when the family
      does not furnish the child with a feeling of security. Very often it becomes the
      main reason for the development of fears, including separation fear. The
      described study of the child suffering from separation fear testifies to a strong
      interrelation between the attitude of the parents, their volatile feeling of
      security, an the fear developed by the child. It also demonstrates the influence
      of the generic families on the current family situation. All these factors prove
      that there should be a strong relation between the child therapy and the family
      therapy. All the described forms of therapy account for work with the child in
      the conditions of the day ward according to the Good-Start Method, V. Sherborne,
      group therapy and system family therapy. The interesting point is the stage at
      which the family decides to undergo the therapy and consequently break it up.

PMID- 7568523
TI  - [Psychoorganic and depressive syndrome in severe hepatic diseases].
AB  - Authors present the occurrence of the psychopathologic disorders in the group of
      33 patients (23 women and 10 men) with severe hepatic disorders (mostly cirrhotic
      non-alcoholic). Patients in the 20-69 age range were treated in the Medical
      Academy in Gdansk in the years 1989-1993. 15 patients were examined twice at
      intervals from 6 months to 3 years. Using the Hamilton Depression Scale and
      psychiatric examination, the authors found depression in 5 cases. These patients
      were treated with thymoleptic. On the basis of the Organic Brain Damage Rating
      Scale (by Jarema M. and others) and psychiatric examination, the psychoorganic
      syndrome was confirmed in 4 cases. Correlation between the psychopathologic
      disorders and changes in some biochemical indicators was not found.

PMID- 7568524
TI  - [Repetitive transcranial magnetic stimulation: EEG, serum prolactin and cortisol
      studies in humans].
AB  - Ten adult volunteers had EEG recordings and serial serum prolactine/cortisol
      estimations performed during repetitive transcranial magnetic stimulation. No
      significant changes in either the hormone values or in the EEG traces were
      detected.

PMID- 7568522
TI  - [Neuropsychological description of memory impairment following cortical and
      subcortical brain injuries].
AB  - This article, basing on experimental analysis and clinical observations, focuses
      on the role of subcortical structures in memory processes. It explained
      terminological problems and defined terms of memory: immediate, delayed, recent,
      remote, declarative and procedural. The present article pointed out functional
      hemispheric specialization as a predicator of material-specific forms of memory.
      Neuroanatomical basis was revealed, especially limbic system with its connections
      to prefrontal, cortical and brain stem regions. Amnesic Korsakoff and Wernicke
      syndromes, transient global amnesia, memory loss after bilateral damage of
      temporal lobes and after anterior communicating artery aneurysm rupture, were
      also discussed. Next part exhibited current knowledge about definition of
      dementia which may be caused by many multi-focal brain diseases like multiinfarct
      (vascular) dementia, Parkinson disease, Huntington disease, and sclerosis
      multiplex, and compared to Alzheimer disease. Term of dementia was defined,
      according to Cummings and Benson, as syndrome of acquired intellectual
      dysfunction when three of the following mental functions are impaired: language,
      memory, visuospatial skills, emotion, and cognition (abstraction, calculation,
      judgement). There is little doubt that various subcortical diseases are
      characterised by similar, no specific dysfunctions of cognitive processes
      including: disturbed attention and concentration, slowness of mental processing,
      forgetfulness, personality alterations and mood disturbances as well as
      motivational impairment, visuospatial disturbances, absence of symptoms of
      cortical dysfunction such as aphasia, agnosia and apraxia and associated motor
      disorder. Review of the literature suggests that rapid forgetting and retrieval
      deficits are most often symptoms of memory deficits observed after subcortical
      brain injuries.

PMID- 7568525
TI  - [A case of serotonin syndrome].
AB  - A minority of patients treated with serotonergic agents develop a fulminant and
      potentially life-threatening illness characterized by changes in mental status,
      restlessness, myoclonus, hyperreflexia, tremor, shivering, incoordination,
      hyperthermia, diaphoresis and diarrhea. This condition of serotonergic
      hyperstimulation is called the "serotonin syndrome". The author describes an
      adverse response in a patient given fluoxetine and lithium. A 61-year-old woman
      presented to casualty exhibits nearly all of the diagnostic criteria proposed by
      Sternbach [17].

PMID- 7568526
TI  - [Serum lipid peroxides in alcoholic patients].
AB  - The study presents the estimations of serum lipid peroxide (LPx) concentrations
      in alcoholic patients during acute ethanol intoxication and in abstinence period.
      The increase of lipid metabolism in alcoholic drunkenness suggests that LPx plays
      marked role in this turnover.

PMID- 7568528
TI  - Characteristics of HIV-positive chronically mentally ill inpatients.
AB  - The growing population of chronically mentally ill persons who are HIV-positive
      or who have AIDS has not yet been adequately studied. We describe the entire
      population of known HIV-positive inpatients in a state psychiatric center in New
      York City. In this sample, the typical patient with known HIV infection is as
      likely to be a man as a woman and is a member of an ethnic minority group. HIV
      positive patients had multiple risks for HIV infection including injecting drug
      use (IDU), sex with IDU partners, prostitution and male homosexual activity. Most
      patients were at a late stage of HIV-infection, typically with CD4+ cell counts
      of 400. Discharge plans were complicated by HIV illness and most HIV-positive
      patients had a longer length of hospital stay than non HIV-positive patients. We
      discuss the need to plan for the management of increasing numbers of HIV-positive
      patients in inpatient, outpatient, and residential facilities.

PMID- 7568529
TI  - Clinical and administrative consequences of a reduced census on a psychiatric
      intensive care unit.
AB  - The Psychiatric Intensive Care Unit at the FDR VA Hospital is a specialized ward
      designed to assess and treat suicidal and assaultive patients. Since its creation
      in 1983, over 1600 admissions have taken place. The authors have previously
      reported that patients referred for aggressive behavior had a statistically
      significant higher recidivism rate, as well as a statistically significant longer
      length of stay. The unit went through several changes in response to externally
      perceived needs and available resources. When the census cap was decreased, the
      referral pattern changed and the patients were even more likely to be aggressive.
      Length of stay decreased dramatically leading to a unit with a significantly
      higher turnover rate. Clinical and administrative concerns are also discussed.

PMID- 7568527
TI  - [Psychopathological symptoms in atypical viral hemorrhagic tick-borne
      encephalitis].
AB  - A 17 year old boy was admitted because of symptoms of a catatonic syndrome.
      During the diagnosis we ascertained that there was bleeding from the central
      nervous system of unknown origin. The intensification of neurological and general
      symptoms/among others-hyperthermia/suggested haemorrhagic encephalitis, which was
      confirmed by the viral investigation of the cerebrospinal fluid (tick-borne
      encephalitis). We describe this case because viral encephalitis rarely has
      haemorrhagic effects. Usually tick-borne encephalitis is of diphasic type with
      the attacks of "epilepsia partialis continua", which were not observed in this
      case.

PMID- 7568531
TI  - The state psychiatric center as an academically affiliated tertiary care
      hospital.
AB  - Conventional wisdom views state psychiatric hospitals as a problem as much as a
      solution in the fight against mental illness. The legacy of the historic
      shortcomings of these hospitals--overcrowding, dreary environment, ineffective
      treatments, understaffing--frames the discussions of their future. The authors
      argue that a positive, constructive mission and vision for state hospitals is
      emerging in New York. This vision calls for fewer, smaller, specialized centers
      redefined as academically affiliated, community based, consumer oriented,
      tertiary care centers. To transform these centers, a major reengineering is
      proposed, including centralized treatment, patient and family participation,
      continuing education for all staff, outcome research, specialization, multi
      service campuses, and technology transfer programs. With this transformation,
      State Psychiatric Centers become partners in efforts to improve the quality of
      life for people with mental illness throughout society.

PMID- 7568530
TI  - A biopsychosocial rationale for coerced community treatment in the management of
      schizophrenia.
AB  - Coerced community treatment in its various forms is receiving increasing
      attention and generating considerable controversy. Few attempts, however, have
      been made to articulate a rationale for its use. The author presents material in
      support of the concept that schizophrenia can be viewed as a set of
      biopsychosocial deficits and that some of the deficits can be efficaciously
      addressed using coerced community treatment. The biological, psychological, and
      social deficits are each examined and then a biopsychosocial-coerced intervention
      hypothesis is generated. The underpinning of the use of coerced community
      treatment in this model is its ability to affect structure and motivation and
      thereby to alter the customary community living equation. The charge that one can
      just treat the deficits and then coercion becomes superfluous is answered. The
      concerns that the employment of coercion could become too widespread or be used
      in lieu of adequate community resources for mental health services are also
      considered. The conclusion is that coerced community treatment is a logical
      component of the treatment of schizophrenia in outpatient settings.

PMID- 7568533
TI  - Acute and chronic psychiatric care: establishing boundaries.
AB  - Despite advances in psychiatry, a proportion of those with mental illness have
      episodes of severe illness, and a few of these patients may attain only partial
      recovery. In this respect, mental illness is similar to physical illness and
      systems of acute and chronic care are essential. As mental health care financing
      and delivery systems undergo further flux and reform, we will require clear,
      consensually developed definitions of levels of care, especially because of the
      complexities created by a legacy of a 2-tiered, public and private mental health
      system. This paper first will offer definitions and examples of acute and chronic
      illness and care. We will also address certain problems inherent to such a
      classification. We will then consider principles of and potential plans for a
      system of financing and care for the chronically mentally ill. Two existing plans
      will be reviewed as illustrations of innovations in chronic care. As health
      reform changes the financing and delivery of care for the mentally ill, an
      opportunity exists to integrate public and private monies and services and to
      improve upon the care of the acutely and chronically mentally ill.

PMID- 7568532
TI  - Consumer case management and attitudes concerning family relations among persons
      with mental illness.
AB  - Data from 91 clients participating in a clinical trial of consumer case
      management services were analyzed to determine if there is a relationship between
      client satisfaction with family relations and the amount of community treatment
      services, including case management. It was found that clients' greater face to
      face contact with case managers was related to less satisfaction with family
      relations after one year of service. The analysis provides some support for the
      hypothesis that case managers may be serving some of the functions that have
      traditionally been served by the families of mentally ill clients. Another
      conclusion that could be supported by this analysis is that the degree of
      intensity of case management services has an impact on family relations.

PMID- 7568534
TI  - Substance abuse and lifestyle among an urban schizophrenic population: some
      observations.
AB  - While substance-abusing, schizophrenic populations have been the focus of recent
      research inquiries (Cuffel et al. 1993; Dixon et al. 1990; Drake et al. 1989;
      Miller and Tannenbaum, 1989; Mueser et al. 1990), few researchers have attempted
      to address the prevalence of drug and alcohol abuse among an urban, poor,
      predominantly minority schizophrenic patient group (Drake et al. 1989).
      Furthermore, we know of no published account that attempts to document, using
      ethnographic data, the strategies these patients use to acquire drugs and/or
      alcohol, and the lifestyles associated with such substance use. The majority of
      the patients in our research are African-American (roughly 80%) and almost all
      are on medical assistance, pointing to an indigent population with few external
      resources and little expendable income.

PMID- 7568535
TI  - The experiences of long-stay inpatients returning to the community.

PMID- 7568536
TI  - A comparison of two modalities of cognitive therapy (individual and marital) in
      treating depression.
AB  - Historically, depression was explained and treated intrapsychically and/or
      biochemically. In the 1970s theoretical propositions and treatment applications
      began to appear that offered that depression should be viewed cognitively (Beck
      1963, 1974; Beck et al. 1979) or interpersonally (Coyne 1976a, 1976b; Klerman et
      al. 1984). Simultaneously, though more sporadically, marital interventions
      started to attract interest (Feldman 1976; Friedman 1975). The cognitive and
      interpersonal trends of thinking stimulated researchers to investigate the
      efficacy of these therapeutic modalities and to compare them with each other.
      Interest in these two treatments peaked with the publication of the study that
      emerged from the National Institute of Mental Health (NIMH) Treatment of
      Depression Collaborative Research Program (Elkin et al. 1989). This well-known
      research found that the two psychotherapies were similarly effective, but that
      the interpersonal approach was slightly more successful with more severely
      depressed patients.

PMID- 7568537
TI  - Effects of the experience of depression: application of focus group and survey
      methodologies.
AB  - The popularity of cognitive theories of depression has not appreciably increased
      attention to the effects of depression on how its sufferers subsequently think
      about themselves and structure their lives. As a first step in a program of
      systematic research, we recruited recent and former depressed psychiatric
      patients to participate in focus group discussions of their experience of
      depression and how it has affected them. Statements elicited in two focus groups
      were classified into eight categories: lack of energy and the loss of self
      efficacy, fear of recurrence, fear of taking risks, inability to trust oneself,
      self-presentation and concealment, concern about being a burden to others,
      secondary guilt about having been depressed, and reduced involvement in
      interpersonal relationships. These results were then used as the basis for the
      construction of a survey instrument, the Self-Appraisal Questionnaire (SAQ), and
      strong differences were found between recently recovered depressed women and a
      sample of women without a history of depression. Taken together, results of the
      focus groups and the survey study support the utility of a limited "sick role"
      for recovering depressed persons.

PMID- 7568539
TI  - Measuring therapeutic interactions: research and clinical applications.
AB  - There has been an increasing concern in the family therapy literature about the
      importance of various relationship factors to family therapy outcome. In part,
      this concern stems from the mounting empirical evidence suggesting that the
      therapeutic alliance is a robust predictor of treatment outcome.

PMID- 7568540
TI  - The debate over recovered memory of sexual abuse: a feminist-psychoanalytic
      perspective.
AB  - This paper presents a feminist-psychoanalytic analysis of the contemporary debate
      over the veracity of memories of sexual abuse recovered in treatment. Clinical
      discourse is currently divided between those who argue that recovered memories
      are veridical accounts of sexual trauma and those who claim that many therapists
      are creating memories of abuse in their patients. I present here an analysis of
      the debate on recovered memory and of the social dynamics underlying it, and
      discuss how these dynamics have shaped clinical practice. In exploring the
      clinical issues raised by the debate, I reassess Freud's abandonment of seduction
      theory and explore some of the problematic issues in separating fantasy and
      memory in female psychosexual development. Conflictual aspects of female
      development are situated in an analysis of patriarchal social relationships that
      continue to mediate feminine experience. I argue that the jettisoning of the
      concept of fantasy in much of the clinical literature on sexual abuse has
      contributed to a reification of memory-that is, as "true" or "false"- and a
      sacrifice of complexity in the clinical elaboration of women's abuse experiences.
      In reclaiming the concept of fantasy, I explore a range of meanings located
      between the imaginary and the "real" suggested by female narratives of sexual
      abuse.

PMID- 7568538
TI  - Family images of borderline adolescents.

PMID- 7568541
TI  - Personality traits in schizophrenia.
AB  - In recent years there has been a renewed interest in the integration of
      descriptive and interpersonal approaches to mental illness. Much of the impetus
      for this stems from the introduction in 1980 of the Diagnostic and Statistical
      Manual of Mental Disorders, 3rd edition (DSM-III) (American Psychiatric
      Association 1980), with subsequent research and clinical reports documenting
      important interactions between Axis I syndromes and Axis II personality trait
      factors. While many research efforts have described comorbidity in affective and
      anxiety disorders, less attention has been directed toward clarifying the
      relationships between stable and enduring character traits and Axis I symptoms in
      schizophrenia. In this paper we propose that schizophrenic patients display both
      adaptive and pathological personality traits throughout the illness, and that
      clinical and research efforts to address the interactions between syndromic and
      personality factors ("trait-state" interactions) will further our understanding
      of patterns of symptom presentation and treatment response in these patients.

PMID- 7568542
TI  - Anger attacks in eating disorders.
AB  - As central nervous system serotonergic dysregulation has been postulated to exist
      in both eating and aggression disorders, we hypothesized that anger attacks would
      be more common among patients with eating disorders than among control subjects.
      In addition, we wanted to examine possible relationships between the presence of
      anger attacks and the type or severity of the eating disorder. Subjects were 39
      normal female volunteers and 132 female outpatients with anorexia nervosa,
      bulimia nervosa, or both. Forty-one (31%) of the patients met criteria for anger
      attacks compared with four (10%) of the control subjects. Bulimic patients
      reported the highest prevalence of anger attacks to be associated with greater
      severity of illness. In addition, patients with eating disorders who have anger
      attacks had significantly more depressive symptoms than patients without these
      attacks. Central serotonergic function is involved in such diverse processes as
      feeding behavior, mood regulation, and anger and aggression. The higher
      prevalence of anger attacks among patients than among control subjects may
      reflect central hyposerotonergic function, found in previous studies to be
      present in both eating disorders and pathologic aggression. Supporting this
      interpretation is the finding that the prevalence of anger attacks increased,
      although nonsignificantly, with the severity of bulimia, which has previously
      been shown to be inversely correlated with central serotonergic activity.

PMID- 7568544
TI  - Effect of light therapy on salivary melatonin in seasonal affective disorder.
AB  - To investigate the role of a light-induced advance in the timing of the melatonin
      rhythm in seasonal affective disorder, 11 depressed patients underwent 2 weeks of
      light therapy with full spectrum or cool white light. Evening saliva samples were
      collected before and after each week of treatment and assayed for melatonin to
      determine the time of onset of nocturnal secretion. Both treatments reduced
      depression scores, advanced the timing of the melatonin rhythm, and increased
      melatonin concentrations. Time of onset of the nocturnal increase in melatonin
      did not differ between clinical responders and nonresponders, suggesting that a
      phase advance in the onset of nocturnal melatonin secretion is not sufficient to
      induce clinical remission in seasonal affective disorder.

PMID- 7568543
TI  - A twin study of non-alcohol substance abuse.
AB  - Except for alcohol abuse, little is known about the familial aggregation for
      substance abuse. Here we report twin resemblance for non-alcohol substance use in
      the Washington University Twin Series, wherein probands were identified by
      consecutive admission to psychiatric facilities in the St. Louis area. A 5-point
      substance abuse scale was constructed with values anchored by never used drugs
      (1) to drug dependence (5). Year of birth was the most powerful predictor of drug
      use--younger twins scored far higher than older twins. Either heritability or
      common environment had to be included in the regression model to avoid a
      significant drop in explained variance, but which was more important could not be
      resolved. The correlation for identical twins exceeded that for fraternal twins,
      suggesting the possibility of a heritable factor.

PMID- 7568545
TI  - Maximum variance of late component event related potentials (190-240 ms) in
      unmedicated schizophrenic patients.
AB  - The averaging of individual late component event related potential (ERP)
      responses, particularly P300, has revealed significant differences between
      schizophrenic patients and normal subjects. However, the averaging process
      removes the variability of the individual epochs that constitute that average.
      The response-variance-curve (RVC) method quantifies the variability of the
      individual epochs and allows examinations of windows of maximum variance. In this
      study, we examine the complementary nature of the RVC method to the traditional
      averaging approach. The averaged N200 and P300 ERP components differed
      significantly between the schizophrenic and normal groups, but not between the
      unmedicated and medicated schizophrenic patients. The RVC measure, on the other
      hand, revealed systematic differences in variability, maximal between 190 and 240
      ms, between the unmedicated and medicated schizophrenic patients. The RVC measure
      therefore provides a focused time frame in which to examine dysfunctions in
      information processing and macroscopic scale changes in brain function due to
      medication.

PMID- 7568546
TI  - Event related response variability in schizophrenia: effect of intratrial target
      subsets.
AB  - The response-variance-curve (RVC) method quantifies the variability of the
      individual epochs that constitute the average event related potential (ERP),
      providing complementary information to that offered by ERPs. Numerous studies
      have found that average ERP late components of an auditory "oddball" paradigm can
      differentiate schizophrenic patients from normal subjects. Our previous study of
      the RVC measure revealed significant differences between medicated and
      unmedicated schizophrenic patients in the maximum ERP variability from 190 to 240
      ms. In the present study of unmedicated schizophrenic patients and normal control
      subjects, we examined the influence of intertarget intervals (generated by
      pseudorandom stimulus sequences in an auditory oddball paradigm) on the
      intratrial effects of ERP variability measured by the RVC. The ERPs of
      unmedicated schizophrenic patients were characterized by an instability in a
      latency window corresponding to the N200 component. The effect was particularly
      large at an intertarget interval of 7.8 s and was significantly reduced on either
      side of this intertarget interval.

PMID- 7568548
TI  - Nonlinear analysis of sleep EEG data in schizophrenia: calculation of the
      principal Lyapunov exponent.
AB  - The generating mechanism of the electroencephalogram (EEG) points to the
      hypothesis that EEG signals derive from a nonlinear dynamic system. Hence, the
      unpredictability of the EEG might be considered as a phenomenon exhibiting its
      chaotic character. The essential property of chaotic dynamics is the so-called
      sensitive dependence on initial conditions. This property can be quantified by
      calculating the system's first positive Lyapunov exponent, L1. We calculated L1
      for sleep EEG segments of 13 schizophrenic patients and 13 control subjects that
      corresponded to sleep stages I, II, III, IV and REM (rapid eye movement), as
      defined by Rechtschaffen and Kales, for the lead positions Cz and Pz. During REM
      sleep, for both electrode positions, the principal Lyapunov exponent L1 was
      significantly increased in schizophrenic patients compared with control subjects.
      This finding points to altered nonlinear brain dynamics during REM sleep in
      schizophrenia.

PMID- 7568547
TI  - A comparison of period amplitude and power spectral analysis of sleep EEG in
      normal adults and depressed outpatients.
AB  - Three experiments were carried out to evaluate the relationship between two
      techniques for quantifying electroencephalographic (EEG) data during sleep:
      period amplitude analysis (PAA) and power spectral analysis (PSA). In Experiment
      1, canonical correlations and regression analyses were computed on PSA and PAA
      data from 40 undergraduate volunteers. The results yielded an average canonical
      correlation of 0.98. Further, multiple regression analyses demonstrated that the
      PSA variables accounted for approximately 66% of the variance in the PAA data,
      whereas PAA variables captured 88% of the variance in the PSA data. Epoch-to
      epoch correlations were higher for PAA measures than for PSA data, perhaps
      indicating greater stability of PSA measures across epochs of sleep. In
      Experiment 2, PSA and PAA data were compared in 17 unmedicated outpatients with
      unipolar depression. Canonical correlations and regression analyses indicated
      that the overlap in variance between PSA and PAA did not exceed 50%, regardless
      of whether PSA or PAA variables were used as predictors. Epoch-to-epoch
      correlations between PAA measures were significantly higher than correlations
      among PSA variables, again suggesting greater stability of PAA data across epochs
      of sleep. The range of correlations for either data set was, however,
      substantially lower in the depressed than in the normal group. Experiment 3
      evaluated the possibility that filter settings and artifact-rejection procedures
      had contributed to reduced overlap in PSA-PAA variance and reduced stability in
      depressed patients. An additional group of eight healthy volunteers served as
      subjects. Findings in Experiment 3 indicated that methodological differences
      between Experiments 1 and 2 did not account for the reduced correlations in the
      depressed group. It was concluded that PSA and PAA data should be comparable in
      normal subjects but are relatively independent in depressed patients. Epoch-to
      epoch correlations were higher for PAA data than those found between PSA measures
      in both normal subjects and depressed patients, suggesting that PAA may be more
      stable across sleep epochs. Reduced stability may be a reflection of
      nonstationarity in the EEG of depressed patients.

PMID- 7568549
TI  - Normalization of the auditory P50 gating deficit of schizophrenic patients after
      non-REM but not REM sleep.
AB  - Diminished suppression of the P50 response to repeated auditory stimuli is one
      example of a deficit in elementary sensory processing in schizophrenia. Normal
      subjects suppress the response to the second of two paired auditory stimuli.
      Although normal suppression is occasionally observed in schizophrenic patients,
      it generally disappears with subsequent testing. We have previously reported that
      slow wave sleep (SWS) transiently normalized suppression in schizophrenic
      patients and that the degree of suppression was positively correlated with the
      depth of SWS attained. We hypothesized that schizophrenic patients may have a
      defect that causes a neuronal mechanism to fail after brief use and that its
      activity can be restored by a transient period of inactivity. The present study
      examined whether this effect of sleep in schizophrenic patients is specific to
      SWS or is due to nonspecific factors involved in any period of unconsciousness.
      After baseline recordings, 10 schizophrenic subjects were allowed a period of
      sleep until they attained rapid-eye-movement (REM) sleep. They were awakened at
      the end of the REM period, and postsleep recordings were obtained. REM-stage
      sleep failed to normalize suppression in any of the schizophrenic subjects. P50
      suppression was subsequently assessed after a period of non-REM (NREM) sleep.
      Subjects who reached stage-2 sleep did demonstrate a transient correction in
      auditory gating. These results replicate our previous findings and suggest that
      the sleep effect is specific to NREM sleep. A desensitized nicotinic receptor
      that is resensitized during cholinergic inactivity in NREM sleep is one possible
      mechanism for this effect.

PMID- 7568551
TI  - Effects of isoproterenol infusions on heart rate variability in patients with
      panic disorder.
AB  - Some evidence suggests that patients with panic disorder have a decreased cardiac
      vagal and a relatively higher sympathetic activity. In this study, spectral
      analysis of the time series of heart rate before and after isoproterenol
      infusions was used to study heart rate variability in six panic disorder patients
      and 11 normal control subjects. These preliminary data reveal a significant
      increase of sympathovagal ratios only in the patient group after isoproterenol
      administration. The findings suggest a relative increase in cardiac sympathetic
      and a relative decrease in cardiac vagal function in patients with panic disorder
      during isoproterenol infusions.

PMID- 7568552
TI  - Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L
      methionine.
AB  - A possible method of reducing the delay in antidepressant response is to use S
      adenosyl-L-methionine (SAMe), a naturally occurring compound that appears to have
      a rapid onset of effect in the treatment of depression. In this open, multicenter
      study, 195 patients were given 400 mg of SAMe, administered parenterally, for 15
      days. Depressive symptoms remitted after both 7 and 15 days of treatment with
      SAMe, and no serious adverse events were reported. Further studies with a double
      blind design are needed to confirm this preliminary indication that SAMe is a
      relatively safe and fast-acting antidepressant.

PMID- 7568553
TI  - Psychoeducation and expressed emotion in bipolar disorder: preliminary findings.
AB  - A multifamily psychoeducational intervention was carried out in patients with
      bipolar disorder. The study explored (1) the effects of the intervention on the
      level of expressed emotion (EE) of key relatives; (2) the validity of EE defined
      by a 5-min speech sample as a predictor of relapse; and (3) the evaluations of
      the intervention program by patients and key relatives. Four key relatives in the
      treatment group, compared with none in a waiting list control group, changed from
      high to low EE levels. The change was clinically but not statistically
      significant, perhaps because of the small sample size. Patients whose key
      relatives had low EE levels had a significantly lower number of relapses and
      hospital admissions compared with those whose key relatives had high EE levels.
      The psychoeducational program was well received by all participants, and there
      were no dropouts.

PMID- 7568550
TI  - Identifying delirious states and autonomic cardiovascular dysfunction associated
      with amitriptyline treatment by standardized analysis of heart rate.
AB  - Ninety-one patients treated with amitriptyline and 60 normal control subjects
      underwent a standardized heart rate analysis in supine posture. Tests included
      the determination of time- and frequency-derived measurements of heart rate
      variability. The patients differed significantly from the control subjects in all
      parameters investigated. Two-thirds of the patients treated with a tricyclic
      antidepressant (TCA) reached values that met the criteria for cardiovascular
      autonomic neuropathy. Our results provide evidence that heart rate analysis might
      be a more sensitive tool in diagnosing amitriptyline-associated anticholinergic
      delirium than determination of TCA plasma levels. Further research is needed to
      elucidate what implications the TCA-associated alteration of autonomic
      cardiovascular function might have for patients.

PMID- 7568554
TI  - Relationship of generalized anxiety symptoms to urinary 5-hydroxyindoleacetic
      acid and vanillylmandelic acid.
AB  - Urinary levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA)
      and the norepinephrine metabolite vanillylmandelic acid (VMA) were measured in 45
      patients with generalized anxiety disorder. Multiple regression analysis
      demonstrated that the severity of several anxiety symptoms was predicted by
      levels of 5-HIAA and VMA. These data are consistent with the proposal that
      serotonin and norepinephrine may be involved in the pathophysiology of anxiety.

PMID- 7568555
TI  - Attention deficit hyperactivity disorder and whole-blood serotonin levels:
      effects of comorbidity.
AB  - Whole-blood serotonin (5-hydroxytryptamine, 5-HT) levels were measured in
      children with attention deficit hyperactivity disorder (ADHD) with and without
      comorbid conduct disorder (CD) or oppositional-defiant disorder (ODD). It was
      hypothesized that the whole-blood 5-HT levels of ADHD probands would be
      significantly correlated with the whole-blood 5-HT levels of their mothers. Fifty
      two children who met DSM-III-R criteria for ADHD were selected consecutively from
      an ADHD clinic (47 males--35 Caucasians, 10 African-Americans, and 2 Hispanics;
      10 females--all Caucasians). Whole-blood 5-HT was assayed by high performance
      liquid chromatography and compared between ADHD children with and without
      comorbid CD or ODD. The familiality of whole-blood 5-HT levels was studied by
      Spearman's rank-order correlation. There were no significant age, race, or sex
      effects. There was no significant difference in whole-blood 5-HT levels between
      children with ADHD only (n = 22; 190 +/- 45 ng/ml) and ADHD with CD or ODD (n =
      30; 212 +/- 67). However, 7 out of 30 (23%) children with ADHD+CD/ODD had whole
      blood 5-HT levels > 270 ng/ml, while none of the ADHD-only children had whole
      blood 5-HT levels > 270 ng/ml, a statistically significant difference. Whole
      blood 5-HT levels showed significant positive correlations between 36 children
      with disruptive behavior disorders and their biological mothers (rs = 0.47).
      There was no difference in mean levels of whole-blood 5-HT between subgroups of
      children with ADHD with or without comorbid CD or ODD.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7568557
TI  - Sensitive assay of thyroid stimulating hormone in depressed patients.
AB  - A decreased thyroid stimulating hormone (TSH) response to thyrotropin releasing
      hormone (TRH) has been noted in major depression. Some authors found a positive
      correlation between baseline TSH levels and TSH response to TRH, especially with
      sensitive assays of TSH. Serum TSH was assayed by a sensitive method in 55
      depressed patients and 38 healthy volunteers. Patients were subclassified
      according to DSM-III as suffering from major depression (n = 40) and non-major
      depression (n = 15). The patients' mean score on the Hamilton Rating Scale for
      Depression (HRSD) was 50 (SD = 10). The TSH value was significantly lower in
      depressed patients compared with healthy control subjects, and in major compared
      with non-major depression. No differences in TSH levels distinguished the various
      subtypes of major depression. There was a significant negative correlation
      between global HRSD scores and TSH concentrations. The most anxious patients
      tended to have significantly lower TSH values compared with the least anxious
      subjects. Total HRSD insomnia scores correlated negatively with TSH
      concentrations after log transformation. The sensitive determination of TSH may
      also provide an index of thyroid function in depression that is simpler to
      implement than measurements of the TSH response to TRH.

PMID- 7568558
TI  - Type I and type II schizophrenia: relations between tonic electrodermal activity
      and clinical ratings before and after haloperidol treatment.
AB  - To test the hypothesis that schizophrenic patients with positive vs. negative
      symptoms show different tonic electrodermal patterns, 26 patients with Type I
      schizophrenia and 19 patients with Type II schizophrenia were evaluated before
      and after 2 weeks of haloperidol treatment (standard daily dose = 4.5 mg).
      Clinical assessments were made with the Brief Psychiatric Rating Scale, the Scale
      for the Assessment of Positive Symptoms, and the Scale for the Assessment of
      Negative Symptoms. Skin conductance level (SCL) and spontaneous fluctuations (SF)
      frequency were recorded for each patient. Before treatment, Type I patients
      showed higher SCL and SF compared with Type II patients; after treatment, a
      significative decrease of clinical and psychophysiological variables was found
      only in Type I patients.

PMID- 7568556
TI  - Circadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormones,
      and cortisol in schizophrenia.
AB  - Changes in the circadian rhythmicity in vital signs, catecholamines, thyroid
      hormones, and cortisol have been observed in psychiatric disorders, most notably
      in depression. With respect to schizophrenia, the literature is scanty. We report
      here on the circadian parameter estimates of the vital signs, epinephrine,
      norepinephrine, triiodothyronine, thyroxine, thyroid stimulating hormone, and
      cortisol in the blood of 34 healthy subjects, 89 drug-free schizophrenic
      patients, and 25 neuroleptic-treated schizophrenic patients. The analyses are
      based on the cosine model to fit the experimental data. The circadian profiles of
      heart rate, blood pressure, and oral temperature are similar among schizophrenic
      patients and healthy subjects. Neuroleptic-treated patients have significantly
      higher MESORs (the daily mean) of serum norepinephrine and epinephrine than
      healthy subjects. The TSH MESOR is significantly lower in schizophrenic patients;
      the MESOR of triiodothyronine also shows a tendency to be nonsignificantly lower
      in schizophrenic patients compared with control subjects. The circadian serum
      thyroxine and cortisol profiles are similar in the three groups. The data show
      that the circadian profiles of vital signs in drug-free chronic schizophrenic
      patients who are not chronically hospitalized are similar to those of healthy
      subjects and that the increase in serum catecholamines and the apparent lowering
      in some thyroid indices might induce a down-regulation in the noradrenergic
      receptor system that could contribute to the pathophysiology of schizophrenia.

PMID- 7568559
TI  - Evoked potentials in subjects at risk for Alzheimer's disease.
AB  - Evoked potential (EP) changes accompanying dementing processes have been
      documented in a number of studies. However, EPs have not been studied in subjects
      who are at heightened risk for the development of Alzheimer's Disease (AD).
      Nineteen volunteers with no immediate family members with a history of AD and 33
      healthy subjects with at least one first-degree relative with AD were studied. Of
      the 33 subjects with a positive family history of AD, the illness of the sick
      relative was classified as possible AD in 10 subjects, probable AD in 17
      subjects, and definite (autopsy-proven) AD in 6 subjects. Mid-latency evoked
      potentials (P50, N100, and P200) and P300 event-related potentials were recorded
      in an oddball paradigm. The amplitudes of the P50 responses to the frequent
      stimuli and of the P300 responses were significantly higher in the subjects whose
      relatives had definite AD as compared with the other three groups. The amplitude
      of the N100 component was also larger in the same group, but the difference was
      only statistically significant from the group of healthy volunteers without a
      family history of AD. A process of increased sensitivity to incoming stimuli may
      be reflected in the increased P50, N100, and P300 amplitudes in the subjects at
      increased risk for developing AD.

PMID- 7568560
TI  - Alterations in local cerebral glucose utilization in rats after chronic
      amphetamine administration without subsequent challenge.
AB  - The 2-deoxyglucose (2-DG) method was used to study regional metabolic changes in
      rats following chronic d-amphetamine treatment without subsequent challenges.
      Four groups of rats were pretreated (intraperitoneal administration) with d
      amphetamine (0, 1, 5, or 10 mg/kg) once per day for 14 days. After a 7-day
      abstinence period without further challenge, the 2-DG method was used to measure
      the rates of local cerebral glucose utilization (LCGU). Significant metabolic
      changes among the four groups were found in five brain regions, including the
      nucleus accumbens and the lateral habenular nucleus. Another four groups of rats
      with the same pretreatment regimens, challenged with 5 mg/kg d-amphetamine, were
      used for behavioral testing. The results showed intense stereotyped behaviors in
      the 5 mg/kg and the 10 mg/kg groups. In the steady state, however, there were no
      significant glucose utilization changes in the nigrostriatal system, which is
      thought to be related to stereotyped behaviors. During steady state, metabolic
      changes were found in a limited number of brain regions. No difference in LCGU
      was found in the sensitization-related regions. Further challenges with
      stimulants may be necessary to investigate the metabolic responses after
      sensitization.

PMID- 7568561
TI  - Effect of bright light treatment on agitated behavior in institutionalized
      elderly subjects.
AB  - This study examined whether exposure to bright light treatment would reduce
      agitated behavior in institutionalized elderly subjects. Six demented elderly
      subjects (mean age = 89.2 years) living in a skilled nursing facility were
      studied. Light (2500 lx) was administered for 2 hours in the morning for two 10
      day periods. The Bliwise Agitation Behavior Rating Scale was used to rate
      agitated behavior once every 15 min between 16:00 h and 20:00 h during 3 days of
      baseline, the light treatment periods, and 5 days of posttreatment follow-up
      evaluation. The entire protocol was then repeated in an ABABA design. A planned
      comparison revealed a significant difference between light treatment days and
      nontreatment days, with less agitation being observed on treatment days. The
      study suggests the efficacy of the clinical use of bright light treatment to
      reduce agitation.

PMID- 7568562
TI  - Tone discrimination performance in schizophrenic patients and normal volunteers:
      impact of stimulus presentation levels and frequency differences.
AB  - Psychophysical and cognitive studies carried out in schizophrenic patients show
      high within-group performance variance and sizable differences between patients
      and normal volunteers. Experimental manipulation of a target's signal-to-noise
      characteristics can, however, make a given task more or less difficult for a
      given subject. Such signal-to-noise manipulations can substantially reduce
      performance differences between individuals. Frequency and presentation level
      (volume) changes of an auditory tone can make a sound more or less difficult to
      recognize. This study determined how the discrimination accuracy of medicated
      schizophrenic patients and normal volunteers changed when the frequency
      difference between two tones (high frequency vs. low frequency) and the
      presentation levels of tones were systematically degraded. The investigators
      hypothesized that each group would become impaired in its discrimination accuracy
      when tone signals were degraded by making the frequencies more similar and the
      presentation levels lower. Schizophrenic patients were slower and less accurate
      than normal volunteers on tests using four tone levels and two frequency
      differences; the schizophrenic patient group showed a significant decrement in
      accuracy when the signal-to-noise characteristics of the target tones were
      degraded. The benefits of controlling stimulus discrimination difficulty in
      functional imaging paradigms are discussed.

PMID- 7568564
TI  - Regional cerebral blood flow in mood disorders: IV. Comparison of mania and
      depression.
AB  - Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated,
      relatively young adults in episodes of either acute mania (n = 11) or major
      depression (n = 11) and in matched normal control subjects (n = 11), using the
      133xenon inhalation method, under eyes-closed, resting conditions. The three
      groups were equivalent in global CBF. Both patient groups showed significant
      reductions of rCBF in anterior cortical areas and reduction of the normal
      anteroposterior gradient. In addition, there was evidence of abnormal, albeit
      similar, patterns of flow lateralization on a regional basis in both clinical
      groups compared with normal subjects. An exploratory analysis revealed
      preliminary evidence of rCBF differences between the clinical groups, localized
      to the inferior frontal cortex. Otherwise, the evidence in this study suggests
      that young adult manic and depressed patients are predominantly similar in
      cortical rCBF parameters.

PMID- 7568563
TI  - The P50 evoked potential component and mismatch detection in normal volunteers:
      implications for the study of sensory gating.
AB  - Sensory gating is a complex, multistage, multifaceted physiological function
      believed to be protecting higher cortical centers from being flooded with
      incoming irrelevant sensory stimuli. Failure of such mechanisms is hypothesized
      as one of the mechanisms underlying the development of psychotic states.
      Attenuation of the amplitude of the P50 evoked potential component with stimulus
      repetition is widely used to study sensory gating. In the current study, we
      investigated the responsiveness of the P50 component to changes in the physical
      characteristics of ongoing trains of auditory stimuli. Forty normal volunteers
      were studied in a modified oddball paradigm. At all cerebral locations studied,
      P50 amplitudes were higher in response to infrequent stimuli. We postulate that
      the increase in P50 amplitude reflects the system's recognition of novel stimuli
      or "gating in" of sensory input. The ratio of the amplitude of the responses to
      the infrequent stimuli to those of the frequent stimuli was significantly higher
      for the posterior temporal regions. This finding provides further evidence that
      the temporal lobes may be significantly involved in sensory gating processes.
      Although this study only included normal subjects, the data generated contribute
      to the understanding of sensory gating mechanisms that may be relevant to
      psychotic states.

PMID- 7568565
TI  - Gray matter heterotopias in schizophrenia.
AB  - Gray matter heterotopias (GMHs) are a type of neuronal migration anomaly in which
      collections of normal neurons are abnormally located secondary to an arrest of
      radial migration. They are often manifested clinically by seizures and cognitive,
      motor, and language deficits. Through magnetic resonance imaging, we have
      observed two cases in patients presenting with symptoms of schizophrenia, but no
      neurological abnormalities, and otherwise normal scans. While the incidence of
      GMH among normal individuals is unknown, it is possible that this particular
      anomaly may occur in schizophrenic patients at a higher rate than in the normal
      population. Furthermore, neuronal migration abnormalities may be involved in the
      pathogenesis of the disorder among a small subset of patients with schizophrenia.

PMID- 7568566
TI  - Cerebellar blood flow in schizophrenic patients and normal control subjects.
AB  - We used 133Xe dynamic single-photon emission computed tomography (DSPECT) to
      measure the resting cerebellar blood flow in 17 neuroleptic-free schizophrenic
      and schizophreniform patients and 13 normal control subjects. A subset of these
      subjects (11 patients and 7 control subjects) additionally underwent activation
      studies during the Wisconsin Card Sorting (WCS) and Number Matching (NM) tests.
      Baseline relative cerebellar blood flow was significantly lower in older patients
      than in age-matched control subjects. For absolute cerebellar flow, there was a
      significant difference between patients and control subjects in the overall
      activation response (patients: NM 13.4% increase, WCS 15.7% increase; control
      subjects: NM 3.1% decrease, WCS 0.0% change). This difference was more pronounced
      in older subjects. Cerebral blood flow significantly increased during NM
      (patients: 21.3% increase, control subjects: 6.5% increase) and WCS (patients:
      16.5% increase, control subjects: 9.7% increase). The difference in the magnitude
      of cerebral NM activation between schizophrenic patients and control subjects,
      although not statistically significant, may call into question the
      appropriateness of using NM as a control task in schizophrenic patients. Finally,
      we found no differences between the effects of WCS and NM on cerebellar or
      cerebral blood flow. Because of the small number of subjects in each group, the
      results of this study should be interpreted cautiously.

PMID- 7568567
TI  - Midline abnormalities and psychopathology: how reliable is the midsagittal
      magnetic resonance "window" into the brain?
AB  - The argument is made that mensuration of midsagittal magnetic resonance (MR)
      images is plagued with methodological errors due to confusion of the midsagittal
      MR image and the mesial brain surface. Several examples are given to demonstrate
      the effects of slice thickness and orientation on the size and shape of mesial
      structures. The benefits of examining contiguous slices and the necessity of
      consulting coronal and transaxial cuts in mensuration efforts of midsagittal cuts
      are emphasized.

PMID- 7568570
TI  - Psychological science and the use of anatomically detailed dolls in child sexual
      abuse assessments.
AB  - Many devices are used in child assessment and treatment as communication aids,
      projective tools, and symbolic means of interaction. None are as hotly debated in
      their application among mental health professionals as dolls with genital
      details. Anatomically detailed (AD) dolls are often used in sexual-abuse
      evaluation and treatment with children, but such applications are controversial.
      This article is the product of a working group formed to review AD doll research
      and practice. This article reviews historical use of dolls in clinical inquiry
      and research on sexual behaviors in children, normative use of AD dolls in
      nonreferred children, differences in children's play behavior and emotional
      reactions to AD dolls, and memory and suggestibility issues relating to AD-doll
      use. Recommendations for future research are provided.

PMID- 7568568
TI  - Head motion during positron emission tomography: is it significant?
AB  - High sensitivity for detecting local brain function differences from subsequent
      PET images acquired at different cerebral stimulation states requires interscan
      head motion to be minimized. This motion was measured by an optical lever system
      during scanning (130 min) of 15 subjects in a dual-dose injection study. Despite
      motion restriction by a face-mask restraint system, rotations in the sagittal and
      coronal planes (up to 4.1 degrees and 2.4 degrees, respectively) significantly
      influenced the measured means and variances of local metabolic differences
      between states. Hence, adjustments for head movement by retrospective, digital
      slice realignment or, better, real-time corrections are important.

PMID- 7568571
TI  - Inverse-intensity effect in duration of visible persistence.
AB  - Duration of visible persistence can vary inversely with stimulus intensity. This
      inverse-intensity effect is obtained by varying the intensity of the stimuli or
      of the background, provided that the variations extend into the mesopic range. A
      similar relationship--known as the Ferry-Porter law--holds for the critical
      frequency at fusion (CFF). The authors propose that studies of CFF, 2-pulse
      threshold, and visible persistence can be encompassed within 1 conceptual
      framework in which the effect is modeled by the progressive reduction in the
      temporal extent of the positive phase of the system's response as the level of
      light adaptation changes from scotopic to photopic. In this context, the authors
      present an integrative scheme in which G. Sperling and M. M. Sondhi's (1968)
      formal model and M. Coltheart's (1980) neurophysiological conjecture are shown to
      be compatible and complementary accounts of the effect.

PMID- 7568569
TI  - A comparison of stereology and segmentation techniques for volumetric
      measurements of lateral ventricles in magnetic resonance imaging.
AB  - Lateral ventricular volumes were measured on magnetic resonance imaging (MRI)
      scans by independent raters in 18 subjects (11 psychotic patients and 7 healthy
      control subjects) with two different approaches: a point-counting stereological
      (PCS) technique and a computerized technique based on segmentation algorithms.
      The correlation between the two techniques was very high (r = 0.96), and phantom
      studies showed good validity for both approaches. These findings and the
      technical simplicity of the PCS technique support its potential use for MRI
      morphometric measurements.

PMID- 7568572
TI  - Perspectives of chronic pain: an evaluative comparison of restrictive and
      comprehensive models.
AB  - The authors compare theoretical perspectives of chronic pain using a restrictive
      comprehensive categorization. Four of the perspectives (mind-body dualism,
      psychological, radical operant--behavioral, and radical cognitive) are
      categorized as restrictive. The other 4 perspectives (International Association
      for the Study of Pain, gate control, nonradical operant--behavioral, and
      cognitive-behavioral) that incorporate multiple facets are categorized as
      comprehensive. On the basis of empirical support, practical application, and
      issues concerning potential research design problems, the restrictive
      perspectives could be rejected for not providing a model in which chronic pain
      can be thoroughly investigated. The comprehensive perspectives, however,
      demonstrate greater potential for serving that role. Nonetheless, the need for
      additional theory development by the comprehensive perspectives is noted.

PMID- 7568573
TI  - The application of Fourier deconvolution to reaction time data: a cautionary
      note.
AB  - The Fourier transform method in conjunction with frequency domain smoothing
      techniques has been suggested as a powerful tool for examining components in a
      serial, additive reaction time model (P. L. Smith, 1990). Robustness and
      sensitivity to violations of the assumptions of serial model of this method are
      evaluated. When an incorrect distribution was used in recovering an unobserved
      component, results gave no information to show that an incorrect distribution was
      used, and the results were just as interpretable as those obtained using the
      correct distribution. These results demonstrate that the assumptions underlying
      the method cannot be assessed by the result of deconvolution, and the method
      cannot show that the purported component is actually from the serial combination.

PMID- 7568574
TI  - Self-statements, locus of control, and depression in predicting self-esteem.
AB  - The contributions of frequency of positive and negative self-statements and their
      ratio, locus of control, and depression in prediction of self-esteem were
      examined. Volunteers were 145 college students (100 women and 45 men) who were
      administered the Coopersmith Self-esteem Inventory-Adult Form, Automatic Thought
      Questionnaire-Revised, the Beck Depression Inventory, and the Rotter Internal
      External Locus of Control Scale. Intercorrelations suggested significant
      relationships among variables. The magnitude of the relationship was strongest
      between the frequency of negative self-statements and self-esteem. These results
      are consistent with and lend further support to prior studies of Kendall, et al.
      and Schwartz and Michaelson.

PMID- 7568575
TI  - Tests that are robust against variance heterogeneity in k x 2 designs with
      unequal cell frequencies.
AB  - Heterogeneity of variance produces serious bias in conventional analysis of
      variance tests of significance when cell frequencies are unequal. Welch in 1938
      and 1947 proposed an adjusted t test for the difference between two means when
      cell frequencies and population variances are both unequal. This article
      describes two ways to use the Welch t to evaluate the significance of the main
      effect for two treatments across k levels of a concomitant factor in a two-way
      design. Monte Carlo results document the bias in conventional analysis of
      variance tests and the stable and appropriately conservative results from
      applications of the Welch t to evaluation of treatment effects in the two-way
      design.

PMID- 7568576
TI  - Type A/B behavior and eight basic emotions in 1084 employees.
AB  - We examined the prevalence of Type A/B behavior and Emotion Profiles in 1084
      employees. This report focused on the relationship between Type A behavior and
      eight basic emotion dimensions. Of the 1084 subjects 710 (65%) scored as Type A
      and 374 (34.5%) as Type B. The mean Bortner scores for all subjects were 182.8
      (SD = 33.7), scores on emotional dimensions for Incorporation and Reproduction
      were high, and intensities for Ejection and Destruction were low; mean scores on
      other emotions were normal. Significant differences between Type A and Type B
      scores were found on six emotional dimensions. Subjects classified as Type A had
      ratings lower on trustful, controlled, and timid and higher on aggressive,
      distrustful, and uncontrolled than did persons classified as Type B. There were
      no differences between Type A and Type B scores on the emotion dimensions of
      Reproduction and Deprivation. Our data suggest multiple emotional components may
      comprise the Type A behavior pattern. This is important for behavioral counseling
      programs and early preventive efforts which could be aimed at reducing the
      intensity of Type A behaviors.

PMID- 7568577
TI  - Interrater reliability of the scoring of the screening test of adolescent
      language.
AB  - Group administrations of the Screening Test of Adolescent Language have been
      successful in identifying students with English-language problems among groups of
      university students who include many recent immigrants from southeastern Asia.
      However, scoring several items requires subjective judgement. Accordingly,
      interrater reliability was investigated by having two independent examiners score
      the written responses of 299 first-year medical students at two Australian
      universities. The examiners produced very similar distributions of total scores
      with means of 20.36 and 19.36 and achieved a high agreement in the categorisation
      of students with English problems. The Spearman rank-order correlation of 0.83
      was high and statistically significant from zero.

PMID- 7568579
TI  - Assessing effects of treatment for substance abuse: a further contribution to the
      validation of the Employee Reliability Inventory.
AB  - Scores on a scale designed to assess the likelihood of freedom from job
      disruptive substance use were compared for three groups: (1) individuals whose
      current substance use had disrupted their job performance and necessitated
      treatment, (2) individuals who successfully completed treatment for substance
      abuse, and (3) a representative subset of a geographically and occupationally
      diverse group of job applicants (N > 43,000). The results appear consistent with
      the hypothesis that this scale validly measures behavioral changes related to job
      performance which are associated with successful treatment of substance abuse.
      Scores on the scale differentiated untreated substance users from those who had
      successfully undergone treatment. Scores for the successfully treated group were
      the same as those for the general group of job applicants. That is, scores did
      not differentiate successfully treated former substance users from a general
      group of job applicants. For the subset of the successfully treated group who
      became employed during the study period, scores were better for those individuals
      who successfully completed a minimum of 30 days on the job.

PMID- 7568578
TI  - A forgotten pioneer: Anton T. Boisen and religious psychosis.

PMID- 7568580
TI  - Brief cognitive behavioural therapy with male adolescent offenders in open
      custody or on probation: an evaluation of management of anger.
AB  - A 6-wk. cognitive behavioural program administered to 24 adolescent male
      offenders assigned to open custody and 5 to probation showed no mean differences
      on the Test of Nonverbal Intelligence, the Minnesota Multiphasic Personality
      Inventory, and the Coopersmith Self-esteem Inventory. Significant correlations
      were found for the personality measures with pretreatment and posttreatment
      scores on the Buss-Durkee Hostility Inventory.

PMID- 7568581
TI  - Awareness of time in dementia of the Alzheimer type.
AB  - A prospective study of 35 patients with moderate or mild dementia of the
      Alzheimer type was performed to assess and compare their awareness of time. A
      Mini-Mental Status Examination score was used to separate those 16 patients with
      mild dementia (range, 15 to 24) from those 19 with moderate dementia (range, 7 to
      15). Each patient was scored on awareness of time. Those classified as moderate
      but not those with mild dementia showed significant loss of awareness of time.

PMID- 7568582
TI  - Scores on the SF-36 scales and the Beck Depression Inventory in assessing mental
      health among patients on hemodialysis.
AB  - 45 patients on hemodialysis were administered both the Medical Outcomes Study SF
      36 and the Beck Depression Inventory. The Mental Health Inventory subscale scores
      of the SF-36 were regressed stepwise on the Role Emotional subscale scores of the
      SF-36 and the Beck inventory. 46% of the variance in the MHI-5 scores was
      accounted for by age category and the other two measures of emotional status. Age
      category was not significant. Discussion includes the potential utility of the
      combination of inventories in assessing mental health among patients on
      hemodialysis.

PMID- 7568583
TI  - Alcohol use and risky sex among college students.
AB  - Undergraduates, 55 men and 151 women, completed a 13-item survey about drinking
      behavior and sexual activity. In general, men and women were similar in their
      behaviors. Despite recent efforts to promote AIDS awareness, it appears that both
      genders may be engaging in risky behavior. The results are discussed in terms of
      educational efforts aimed at AIDS prevention.

PMID- 7568584
TI  - The association of alcohol consumption with self-reported illness in university
      students.
AB  - Many reports over the years have indicated an association between alcohol
      consumption and infectious illness among chronic heavy drinkers; however, many
      patients in these studies have been chronically ill. Thus the question of whether
      alcohol can appreciably influence immunity in humans and affect the incidence of
      infectious diseases remains largely unanswered. For this study over 1,100
      undergraduate students from a general education course at a large midwestern
      university were surveyed. Students were asked about their drinking habits and
      acute health problems. Analyses of their self-reports showed no increase in acute
      health problems or upper respiratory infections in students drinking between one
      and 21 drinks per week. However, students drinking 28 or more alcoholic drinks
      per week had significantly more health problems in the aggregate and those
      drinking more than 22 drinks per week had more upper respiratory infections than
      other students including nondrinkers. It was concluded that excessive alcohol
      intake increased the risk of respiratory infections and acute illnesses in these
      students, but more moderate alcohol consumption had little effect on the risk for
      these health problems.

PMID- 7568585
TI  - Interpersonal dependency in alcoholic and obese men.
AB  - While psychological conflict about dependency needs of alcoholic and obese
      persons has been widely observed, few studies have examined differences in
      dependency characteristics between these clinical groups. The Interpersonal
      Dependency Inventory was administered to 22 alcoholic and 8 morbidly obese men in
      intensive treatment for alcohol and obesity. The original hypothesis that
      alcoholic and obese men would show similar dependency needs was supported.
      Dependency correlates of personality may serve as useful predictor variables in
      the clinical treatment of alcoholic and obese persons.

PMID- 7568586
TI  - Parental interest and academic achievement of Xhosa children from broken and
      intact homes.
AB  - This study examined the relationship between parental interest and academic
      achievement of 955 Xhosa-speaking children whose mean age was 15.3 yr. An
      interview schedule was used to estimate parental interest. Analysis of variance
      indicated positive and statistically significant effects of parental interest
      scores on children's achievement in school.

PMID- 7568587
TI  - Changes over time in academic dishonesty at the collegiate level.
AB  - Recent assertions that collegiate cheating has risen dramatically have increased
      in frequency. We examine the possibility that these assertions are based on
      comparisons of studies of different behaviors with varied methodologies, and
      different opportunities to cheat. To assess the increase in cheating we
      identified a cheating behavior which had been empirically studied consistently
      from the early 1900s. When the percentages of students who cheated in these
      studies were compared across time periods, while controlling for methodological
      differences, no significant linear trend was found.

PMID- 7568588
TI  - Memory for parking location in large lots.
AB  - The recall of automobile parking location was assessed over five consecutive
      workdays. Completed data from 36 women and 19 men provided measures of accuracy
      and a survey of specific strategies. Analysis showed a significant recency effect
      with memory for the most recent parking locations being superior. Less variation
      in parking location and shorter distance from parking location to building
      entrance were associated with better recall. Contrary to prevalent belief, older
      subjects had more accurate recall. Older subjects parked closer to the entrance
      and used fewer spaces which were also located closer together. The most
      frequently reported strategy was "favorite location" which was used more often by
      older subjects. Whereas laboratory tasks show memory deficits with increasing
      age, some studies in the natural environment have exhibited less such decline;
      the current data showed an actual improvement. It may be that older people adopt
      and practice compensatory strategies in the natural environment while laboratory
      tasks give little opportunity for establishing or practicing such devices.

PMID- 7568589
TI  - Relation among self-defeating personality, troubled eating patterns, and
      dissociation.
AB  - Significant small correlations were found between scores on a measure of self
      defeating personality with scores on the Bulimia Test-Revised (r = .27) and also
      scores on the Dissociative Experiences Scale (r = .20) for a sample of 165
      college women. The correlation between the Bulimia Test and the Dissociative
      Experiences Scale was .26. Although the research literature led us to expect
      stronger relationships on theoretical and empirical grounds, it appears these
      small relationships were more likely due to the fact that scoring higher on all
      these measures indicates greater psychopathology.

PMID- 7568592
TI  - Machiavellianism and medical career choices.
AB  - Medical career choices and Machiavellianism of 36 junior and 37 senior medical
      students at one private midwestern medical school were studied. Machiavellianism
      was measured by the Mach V Scale. Students choosing psychiatry did not score
      significantly higher on Machiavellianism than those choosing medicine, surgery,
      or other clinical medical specialties. This is contrary to previous research
      which indicated those medical students choosing psychiatry scored higher on
      Machiavellianism. There were no significant differences in Machiavellianism
      scores from two different age groups (20-30 yr. and 31-40 yr.). No significant
      differences were reported in Machiavellianism scores of 45 male and 29 female
      medical students or between junior and senior medical students.

PMID- 7568590
TI  - Barriers and aids in conducting research with older homeless individuals.
AB  - Field notes of a qualitative pilot study of older homeless people in Cincinnati
      identified several barriers and aids to the study of homeless elders. Identified
      research barriers were researcher's lack of contextual wisdom (street smarts),
      locating elders, substance abuse, attrition, victimization, credibility of
      informants, and xenophobia. Identified research aids were friendliness of certain
      elders, openness of the researcher, attractive incentives in exchange for
      interviews, and service providers' willingness to share experiences.

PMID- 7568591
TI  - Risk of HIV transmission in sexual behaviors of college students.
AB  - The purpose of this study was to investigate the sexual behaviors of college
      students and assess the extent to which they were engaging in behaviors that have
      a risk for contracting AIDS. A total of 132 single sexually active students and
      58 married students responded to a survey on their sexual behaviors and
      attitudes. Risk behaviors such as engaging in unprotected sex, having multiple
      sex partners, practicing anal sex, alcohol use, and infidelity and deceptive
      communication with partner were examined. Compared with earlier surveys on the
      same population, there was an increase in concern about contracting AIDS and a
      significant increase in the percentage of students who took the AIDS antibody
      test. Although none indicated they would lie to partners about a seropositive
      AIDS test, a few would not tell their partner unless specifically asked. A small
      percentage of subjects would have extradyadic relations without informing their
      steady partners and a small number of respondents indicated they might continue
      to engage in sexual relations with a seropositive partner or a new partner who
      recently had a seronegative AIDS test. The risks most predominant in this sample
      were the practice of unprotected sex, having multiple sex partners, and the
      consumption of alcohol in conjunction with sexual activity. With the exception of
      unprotected intercourse, the majority of respondents were engaging in behaviors
      that pose a minimal risk for contracting AIDS.

PMID- 7568593
TI  - Scores on psychoticism of adolescent girls in Puerto Rico.
AB  - This study concerns 425 Puerto Rican adolescent girls whose scores on personality
      factors are not consistent. When the Eysenck Personality Questionnaire Junior was
      standardized for Puerto Rico values of factorial comparisons for the female
      adolescents were as low as .65 for Psychoticism. This result points to girls'
      confusion in showing toughness. This might be explained by high expectations but
      there are few opportunities for lower-class girls in a society in which women are
      taught to live around men and not to develop themselves as workers.

PMID- 7568594
TI  - Negative evaluations of men's nurturant touching of young children.
AB  - 82 female and 65 male, mostly unmarried undergraduate students read one of 16
      versions of a brief scenario depicting a man or woman either engaging or not
      engaging in nurturant touching of young children. Subjects then rated story
      characters on masculinity and goodness scales and on scales measuring likelihood
      of social acceptance and future instrumental achievement. Men and women who
      engaged in nurturant touching were rated low on masculinity and high on goodness
      and social acceptance. Men rated male characters lowest on goodness and women
      rated male characters highest on goodness. Women who engaged in nurturant
      touching were given the highest goodness and social acceptance ratings. It was
      concluded that some men may avoid engaging in nurturant touching of young
      children due to gender stereotyping.

PMID- 7568596
TI  - Age differences in social desirability.
AB  - To examine the differences between 162 adolescents' and 118 adults' scores on the
      Eysenck Personality Inventory 64 boys (M age = 20 yr.), 94 girls (M age = 18.9
      yr.), 78 women (M age = 29 yr.), and 40 men (M age = 28.8 yr.) from Umtata and
      the vicinity in Transkei, South Africa were tested. Adolescents scored higher on
      social desirability than adults did.

PMID- 7568595
TI  - Inpatient treatment of mood disorders.
AB  - The present work provides a short-term, intensive, and integrative model for the
      assessment and treatment of mood disorders within a hospital setting. This model
      was developed and implemented at the Milwaukee Psychiatric Hospital in a specific
      inpatient program, a 15-bed unit for patients suffering from dysthymia,
      cyclothymia, major depression, and bipolar disorders. This paper describes the
      program and its philosophy, the target population, and assessment and treatment
      interventions. The data collected included pre- and posttreatment measurements of
      psychopathology and cognitive and emotional functioning for 202 patients.
      Analysis shows the treatment program was effective as scores on measures of mood
      disorders and cognition were reduced from significantly high clinical levels to
      within normal limits. The findings suggest the benefits of using a short-term
      integrative model in the treatment of mood disorders.

PMID- 7568597
TI  - Factors related to loneliness.
AB  - To examine the relations of sex, age, and alcohol with loneliness, 294 subjects
      completed the revised UCLA Loneliness Scale, a 20-item rating scale which
      measures satisfaction and dissatisfaction with current social relationships. A 2
      x 2 x 2 factorial analysis of variance of the loneliness scores indicated a
      significant main effect for age, with older subjects rating loneliness higher
      than younger subjects. There was also a significant interaction between age and
      alcohol use. Older subjects who reported consuming alcohol on more days also
      rated loneliness higher whereas younger subjects who reported consuming alcohol
      on more days were least lonely.

PMID- 7568598
TI  - Improving postpartum marital relationships.
AB  - The effects of a traditional prenatal education program focused on maternal and
      infant physical health education were compared with effects of an innovative
      prenatal program designed to decrease the potentially negative effects of
      childbirth on the quality of marital relationships. 53 couples participated in
      the traditional approach and 63 in the innovative program: all expected a first
      child. Analysis of variance of their scores on the Sexual Relationship Scale and
      also on the Abbreviated Marital Adjustment Scale administered two months
      postpartum (controlled for their scores on the 2 scales before the prenatal
      education program) showed a significant difference between the two groups of
      parents only with respect to sexual relationship: the couples graduating from the
      innovative program were more satisfied with sexual aspects of their marriage
      postpartum.

PMID- 7568600
TI  - Place attachment, isolation, and the power of a window in a hospital environment:
      a case study.
AB  - This paper describes the relevance of the literature on environmental psychology
      to the coping strategies a leukemia patient used in adapting to psychological and
      physical isolation on a hospital bone marrow transplant unit and oncology unit.
      The case study describes the difficulty of place attachment on the isolation unit
      and its evolution on the oncology unit. The power of a window with a natural view
      -including a view of a cemetery--was especially evident even as the disease
      became terminal.

PMID- 7568599
TI  - Teachers' perceptions of occupational stress factors.
AB  - Perceptions of factors in occupational stress were examined using the 17
      elementary and 25 high school teachers' gender, age, experience, and grade
      taught. Statistically significant differences were reported.

PMID- 7568602
TI  - Smoking and trait anxiety.

PMID- 7568601
TI  - Alcohol consumption, locus of control, and self-esteem of high school and college
      students.
AB  - An Alcohol Consumption Questionnaire was designed to investigate 104 high school
      and 104 college students' drinking patterns in actual and hypothetical pleasant,
      unpleasant, and neutral situations. Students were also given Rotter's I-E Locus
      of Control Scale and Rosenberg's Self-esteem Inventory. College students drank
      significantly more than high school students after experiencing hypothetical
      pleasant events. Both groups drank more after hypothetical pleasant events than
      hypothetical unpleasant events and hypothetical neutral events. There were no
      significant group differences after experiencing hypothetical unpleasant events
      or neutral events. Students with high scores on locus of control tended to have
      higher self-esteem, greater drinking after hypothetical unpleasant events,
      hypothetical and actual pleasant events, and hypothetical and actual pleasant
      events, and hypothetical and actual neutral events. Frequencies of actual
      drinking and hypothetical drinking were highly correlated.

PMID- 7568603
TI  - Facilitating changes in exercise behavior: effect of structured statements of
      intention on perceived barriers to action.
AB  - Two groups of worksite employees (58 in a control, 53 in an experimental group)
      underwent three 90-min. educational sessions designed to increase participation
      in exercise. At the end of the third session, experimental subjects were asked to
      complete a structured statement of exercise intention which addressed the major
      barrier to exercise. Two weeks following the program, chi-squared analysis showed
      that the two groups were proportionately different in changes in frequency and
      intensity of exercise such that the experimental group in both cases showed
      greater changes than the control. Experimental subjects showed a twofold increase
      in frequency and intensity of exercise over the control group. Pearson r
      indicated a statistically significant association between the completeness of
      structured statements of intention and an increase in frequency of exercise. We
      conclude that structured statements of intention are useful for distinguishing
      between contrived barriers to exercise (excuses) and actual barriers that require
      practical solutions.

PMID- 7568604
TI  - Convergent validity of the Depression-Happiness Scale with measures of happiness
      and satisfaction with life.
AB  - The aim of the present paper was to investigate the internal reliability and
      convergent validity of the McGreal and Joseph (1993) Depression-Happiness Scale
      with measures of happiness and satisfaction with life. Subjects were 63
      undergraduate students attending the University of Ulster. Internal reliability
      of the scale was .91, and higher scores on the scale were associated with scores
      on the other measures indicating greater happiness and satisfaction with life.

PMID- 7568605
TI  - Childhood abuse as a factor in attrition from drug rehabilitation.
AB  - The following factors were examined as possible influences of clients' attrition
      from inpatient and outpatient drug-rehabilitation programs: depression (Center of
      Epidemiological Studies-Depression test), attributional style (Attributional
      Style Questionnaire), primary drug of choice, family incidence of substance
      abuse, and history of childhood physical abuse. A step-wise regression analysis
      indicated that a history of childhood abuse was a statistically reliable
      predictor of program noncompletion for 92 substance abusers who entered a drug
      rehabilitation program.

PMID- 7568606
TI  - The moderating effect of optimism on the relation between hassles and somatic
      complaints.
AB  - The relations between hassles, dispositional optimism, and prospective reports of
      physical symptoms were examined in a group of 90 Hong Kong undergraduates. Given
      that most hassle scales are confounded by physical and psychological
      symptomatology, a decontaminated scale specifically tailored to the experiences
      of college students was used. Multiple regression analyses indicated that hassle
      scores and the interaction of hassles and optimism uniquely and reliably
      predicted symptom reporting. Optimism, however, did not reliably predict symptom
      reports when effects of hassles and the interaction of hassles and optimism were
      controlled. Inspection of the interaction showed that optimism predicted symptom
      scores only at high levels of hassles. The underlying mechanisms were discussed
      in the light of previous data linking optimism and adaptational outcomes via
      coping. It was suggested that further pursuit of the connection between optimism
      and coping in relation to measures of life stress would be worthwhile.

PMID- 7568607
TI  - Assessment of dissociative identity disorder with the Million Clinical Multiaxial
      Inventory-II.
AB  - 96 patients with a clinical diagnosis of Dissociative Identity Disorder were
      administered the Million Clinical Multiaxial Inventory-II. The most elevated
      personality disorder scales were Avoidant, Self-defeating, Borderline, and
      Passive-Aggressive personality disorders. Elevated Axis I scales included
      Dysthymia, Major Depression, Thought Disorder, and Anxiety Disorder. Million-II
      profiles of a patient before and after integration showed normalization of a
      previously pathological profile.

PMID- 7568608
TI  - Depression in Nigerian and American students.
AB  - 112 college students in America and 180 Muslim Yoruban students in Nigeria
      obtained similar scores on the Beck Depression Inventory. Although they differed
      in their response to seven of the 21 items, no clear general pattern of
      differences emerged.

PMID- 7568609
TI  - Maternal drug use, personality, child-rearing practices, and toddlers' sadness.
AB  - We investigated the influence of maternal drug use/personality attributes and
      child-rearing on 2-yr-olds' sadness. The sample consisted of 62 girls and 53 boys
      and their mothers. Analysis showed maternal parenting practices served as a
      mediator for the effect of the mothers' personalities on the children's feelings
      of sadness. Moreover, the mothers' personality traits of low interpersonal
      difficulty, anxiety, and depression were important in enhancing low maternal
      alcohol or illegal drug use, leading to less sadness in the children.

PMID- 7568610
TI  - Using relaxation techniques and positive self-esteem to improve academic
      achievement of college students.
AB  - This study examined whether after 20 sessions over 10 weeks of Jacobson's muscle
      relaxation accompanied by encouragement of positive self-esteem academic
      examination scores of 22 undergraduate college students would improve by
      comparison with those of a control group of 30 students. The relaxation group had
      significantly higher examination grades than the control group, but there was no
      significant mean difference between the groups on the Cattell and Scheier Anxiety
      Scale or a two-item measure of self-esteem.

PMID- 7568611
TI  - Posttraumatic stress disorder and the MCMI-II.
AB  - This study investigated the MCMI-II profile characteristics of 39 veterans
      diagnosed with Posttraumatic Stress Disorder. Characteristics of the mean group
      profile were similar to prior findings reported in the literature on the MCMI and
      Posttraumatic Stress Disorder with highest mean elevations found on the Avoidant,
      Passive-Aggressive, Schizoid, and Antisocial basic personality scales, the
      Borderline and Schizotypal pathological personality scales, and with elevations
      on the Anxiety, Dysthymia, Alcohol Dependence, Drug Dependence, and Major
      Depression clinical syndrome scales. A multivariate analysis of variance
      comparing the group with Posttraumatic Stress Disorder with a non-PTSD comparison
      group of 39 on the basic personality, pathological personality, and the clinical
      syndrome scales of the MCMI-II was not statistically significant. Nonetheless,
      univariate analyses of variance comparing the two groups on the individual
      modifier scales and the individual personality and clinical syndrome scales of
      the MCMI-II using a Bonferroni adjusted probability indicated significant
      differences on the Desirability and Histrionic scales. Response-style bias as a
      possible factor in MCMI-II profiles for the group with Posttraumatic Stress
      Disorder is also discussed.

PMID- 7568612
TI  - Sense of humor and longevity: older adults' self-ratings compared with ratings
      for deceased siblings.
AB  - 33 older adults (mean age = 72.3 yr.) rated themselves and a deceased sibling on
      the Multidimensional Sense of Humor Scale. A significant mean difference between
      the two groups on the subscale of Humor appreciation suggested the possibility of
      a positive relationship between humor appreciation and longevity.

PMID- 7568613
TI  - An exploration of the relationship between interpersonal problems and
      psychological health.
AB  - The relationship between interpersonal distress and psychological health was
      investigated using a sample of 185 college undergraduates. Subjects completed the
      Inventory of Interpersonal Problems (a measure of interpersonal distress), the
      Personal Orientation Inventory (a measure of self-actualization), and the Miller
      Social Intimacy Scale (a measure of interpersonal closeness). The mean of scores
      on the Inventory of Interpersonal Problems was compared with the mean of the
      clinical sample reported in 1988 by Horowitz, et al. The measures of
      psychological health were correlated with the Inventory of Interpersonal Problems
      total and with the octant scales of the Inventory of Interpersonal Problems
      Circumplex version. The measures were also projected onto the circumplex to
      summarize their interpersonal connotations.

PMID- 7568614
TI  - Accounting for variance shared by measures of personality and stress-related
      variables: a canonical correlation analysis.
AB  - Correlations were computed among the five personality scales of the NEO
      Personality Inventory, two measures derived from the Hassles Scale, and eight
      ways of dealing with stress measured by the Ways of Coping Questionnaire.
      Subjects were 66 undergraduate psychology students. Canonical correlation
      analysis suggests that multivariate procedures treating the data set as a whole
      can detect underlying patterns obscured by large sampling errors at lower levels
      of analysis.

PMID- 7568615
TI  - Dietary iron and exposure to lead influence susceptibility to seizures.
AB  - Previous work in this laboratory showed that concurrent consumption of an iron
      deficient diet and exposure to lead caused seizure activity in Albany
      heterogeneous (HET) stock mice. In the present investigation, 26 Albany HET mice
      (ages 35 to 57 days of age) ate either an American Institute of Nutrition
      approved iron-sufficient (30 ppm) diet or an iron-deficient (less than 3 ppm)
      diet and drank either a 0.5% lead solution or distilled water for 12 weeks. We
      measured several activities in an open-field, hole-board apparatus, and
      spontaneous seizures which occurred during testing, changes in body weight, and
      hemoglobin levels. Replicating previous findings, mice fed the iron-deficient
      diet and treated with lead had more seizures with longer durations and longer
      postictal periods than animals given the iron-sufficient diet but also treated
      with lead. Mice not exposed to lead did not seize. Both lead-treated groups had
      lower rates of body-weight gain over the 3-mo. period and lower hemoglobin values
      than nonlead-treated animals. Changes in activity were observed in the open field
      as a function of diet and exposure to lead.

PMID- 7568616
TI  - Past and current drug use among Canadian correctional officers.
AB  - Current and past drug use was assessed in a sample of 77 Canadian correctional
      officers working in two medium-security penitentiaries. 58% of correctional
      officers indicated past illicit drug use. This compares with 20% of Canadians who
      indicate illicit drug use. Correctional officers were more likely than the
      general population to have used marijuana and cocaine.

PMID- 7568617
TI  - The Child Abuse Potential Inventory: cross-validation in Croatia.
AB  - The aim of this study was to cross-validate the Child Abuse Potential Inventory
      by Milner in Croatia. The inventory was translated and administered to 59 parents
      reported to centres of social work for child abuse or neglect and to a sample of
      383 in the general population of parents. Data on sociodemographic variables and
      socioenvironmental stressors on the family were also collected. A significant
      difference in scores on the inventory's Abuse Scale between groups of parents was
      found. Discriminant analysis indicated an over-all correct classification rate
      for the Abuse Scale of 87.59%. The coefficient of internal consistency for the
      Abuse Scale for all respondents was 0.91. Results were interpreted as supportive
      of concurrent predictive validity in the Croatian sociocultural context.

PMID- 7568618
TI  - Are females' suicides in Japan fatalistic?

PMID- 7568620
TI  - Self-interest and attitudes about legislation controlling alcohol.
AB  - A stratified random sample of 505 adult Indiana residents living in households
      with telephones was surveyed using random-digit dialing to assess their attitudes
      about nine specific legislative proposals to control drunk driving or underage
      drinking and to assess the effects of self-interest on those attitudes. A two
      stage Mitofsky-Waksberg design was used in the computer-assisted telephone
      interview process. There was widespread support for all nine proposals, but self
      interest, related to personal vulnerability for enforcement of those measures,
      reduced the support of regular drinkers for drunk-driving controls compared with
      nondrinkers' support. Parents of children aged 18 and younger were less likely
      than nonparents to support imposing parental liability for the consequences of
      children's underage drinking.

PMID- 7568621
TI  - Comparison of 7-nitroindazole with other nitric oxide synthase inhibitors as
      attenuators of opioid withdrawal.
AB  - Previously, we demonstrated that two nonselective inhibitors of nitric oxide
      synthase (NOS), L-NG-nitroarginine (L-NNA) and L-NG-nitroarginine methyl ester (L
      NAME), reduced some signs of morphine withdrawal in rats. The present work
      extended these studies to include 7-nitroindazole (7-NI), an inhibitor specific
      for cerebral NOS, and N(5)-(1-iminoethyl)-L-ornithine (L-NIO), a potent inhibitor
      of endothelial NOS. Behavioral effects of these four NOS inhibitors and
      clonidine, an alpha 2-adrenoceptor, agonist, on morphine withdrawal in rats were
      assessed. Rats received one 75-mg morphine pellet subcutaneously (SC). Three days
      later, NOS inhibitors were administered IP 1 h before withdrawal was precipitated
      with naloxone (0.5 mg/kg, SC) and scored. 7-NI, L-NIO, L-NAME and L-NNA produced
      dose-related decreases in weight loss, diarrhea, wet dog shakes and grooming. 7
      NI also reduced mastication, salivation and genital effects. Clonidine produced
      effects similar to 7-NI. In awake, morphine-naive and morphine-dependent rats not
      subjected to withdrawal, 7-NI was the only NOS inhibitor that did not increase
      blood pressure. Because 7-NI attenuated more signs of opioid withdrawal than L
      NNA, L-NAME or L-NIO without causing hypertension, 7-NI appears to warrant
      further testing as a potential candidate for human use.

PMID- 7568619
TI  - Clinical psychological students' subjective stress ratings during their doctoral
      training.
AB  - The Bandura-Rosenthal Metrics for Assessing Stress was used to measure perceived
      stress among 25 first and 28 second- and third-year clinical Ph.D. students.
      Analysis gave no significant differences in reported stress across time.

PMID- 7568623
TI  - Effects of caffeine deprivation on complex human functioning.
AB  - Twenty-five managers who reported an average daily caffeine consumption of 575 mg
      participated in two complex simulations. A double-blind cross-over design was
      employed to assess the effects of normal caffeine consumption versus caffeine
      deprivation upon seven validated measures of managerial effectiveness. Data from
      a Caffeine Withdrawal Questionnaire indicated discomfort upon deprivation.
      Systolic blood pressure increased during "normal" caffeine consumption levels but
      fell quickly and remained lower during deprivation. Several measures of
      managerial performance indicated decreased effectiveness upon caffeine
      deprivation. In contrast to prior research from simpler task settings, cognitive
      effectiveness (during complex task performance) was diminished. However, a
      measure of strategic performance which requires a relatively high level of
      cognitive effort showed no impact of caffeine deprivation.

PMID- 7568627
TI  - Effects of neurotensin on EEG and event-related potentials in the rat.
AB  - Neurotensin has neuromodulatory actions on multiple brain functions including
      motor, sensory and limbic processes. However, little is known about how
      neurotensin affects general arousal and/or attention states. The present study
      evaluated the effects of neurotensin on spontaneous brain activity as well as
      auditory evoked responses using electrophysiological measures.
      Electroencephalographic and event-related potential recordings were obtained in
      awake animals following intracerebroventricular administration of neurotensin
      (1.0, 10.0 and 30.0 micrograms). Twenty rats were implanted with recording
      electrodes in the frontal cortex, dorsal hippocampus, amygdala and nucleus
      accumbens. Neurotensin was found to produce a dose-related effect on behavior and
      electrophysiological measures. Lower doses (10 micrograms) produced no obvious
      behavioral changes, but significantly reduced EEG power in the lower frequency
      ranges (2-6 Hz) in the frontal cortex, the anterior amygdaloid complex and the
      nucleus accumbens. At higher doses (30 micrograms), rats appeared behaviorally
      inactivated, and EEG power was reduced in all structures in both the lower
      frequency ranges (2-6 Hz) and the higher frequency ranges (8-32 Hz). Auditory
      processing, as assessed by event-related potentials, was affected most
      significantly in amygdala and dorsal hippocampus. In the amygdala, the amplitude
      of the P3 component of the auditory event-related potential was increased
      significantly by doses of 10.0 and 30.0 micrograms. In the dorsal hippocampus,
      the amplitude and the area of the N1 component was increased dose dependently and
      significance was reached at the 30 micrograms dose. These electrophysiological
      findings indicate that neurotensin does not reduce the arousal level of the
      animals and in fact may enhance neurosensory processing in limbic areas through
      increased arousal and/or enhanced stimulus evaluation.

PMID- 7568625
TI  - The effects of morphine treatment and morphine withdrawal on the dynorphin and
      enkephalin systems in Sprague-Dawley rats.
AB  - The effect of morphine tolerance and withdrawal on prodynorphin peptides was
      studied in relevant brain areas and in the pituitary gland of male Sprague-Dawley
      rats, and compared with effects on the proenkephalin-derived peptide Met
      enkephalin. After 8 days of morphine injections (twice daily), dynorphin A and B
      levels increased in the nucleus accumbens and dynorphin A levels increased also
      in the striatum. Morphine treatment increased striatal Met-enkephalin. Leu
      enkephalinArg6 levels were reduced in the ventral tegmental area (VTA). Morphine
      treated rats had very low Leu-enkephalinArg6 levels in the hippocampus as
      compared to saline control rats. Comparison of the relative amounts of dynorphin
      peptides and the shorter prodynorphin-derived peptides, Leu-enkephalinArg6 and
      Leu-enkephalin, revealed a relative increase in dynorphin peptides versus shorter
      fragments in the nucleus accumbens, VTA and hippocampus. Morphine-tolerant rats
      had lower levels of dynorphin A in both lobes of the pituitary gland, whereas
      hypothalamic dynorphin levels were unaffected by morphine. Leu-enkephalinArg6
      levels were reduced in the hypothalamus, but not changed in the pituitary gland.
      Naloxone-precipitated withdrawal accentuated the increase in dynorphin A and B
      levels in the accumbens and dynorphin A levels in the striatum, while inducing an
      increase in enkephalin levels in the accumbens and Met-enkephalin in the VTA. In
      the hippocampus, Leu-enkephalinArg6 levels remained low in the withdrawal state.
      The low dynorphin levels in the anterior part of the pituitary gland were
      reversed by naloxone, whereas the low dynorphin A levels in the neurointermediate
      lobe were 0ven lower in the withdrawal state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568624
TI  - Dose dependent effects of S-20098, a melatonin agonist, on direction of re
      entrainment of rat circadian activity rhythms.
AB  - The chronobiotic properties of melatonin are well documented. For example,
      following an 8-h phase advance of the light-dark cycle daily injections of
      melatonin administered at the pre-shift dark onset alter the direction of re
      entrainment of rat activity rhythms. Using this 8-h phase advance paradigm, the
      effects of the melatonin agonist S-20098 (1 mg/kg and 3 mg/kg) on the rat
      circadian system were compared with those of melatonin. S-20098 altered the
      direction of re-entrainment in the same manner as melatonin. A study using lower
      doses of S-20098 showed that the effect on direction of re-entrainment was dose
      dependent, with 100% of rats responding at a dose of 100 micrograms/kg. S-20098
      may, therefore, have therapeutic potential as a chronobiotic in the treatment of
      circadian disorders in humans.

PMID- 7568626
TI  - LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors.
AB  - The hallucinogenic effects of lysergic acid diethylamide (LSD) have been
      attributed primarily to actions at serotonin receptors. A number of studies
      conducted in the 1970s indicated that LSD also has activity at dopamine (DA)
      receptors. These latter studies are difficult to interpret, however, because they
      were completed before the recognition of two pharmacologically distinct DA
      receptor subtypes, D1 and D2. The availability of subtype-selective ligands
      (e.g., the D1 antagonist SCH23390) and clonal cell lines expressing a homogeneous
      receptor population now permits an assessment of the contributions of DA receptor
      subtypes to the DA-mediated effects of LSD. The present study investigated the
      binding and functional properties of LSD and several lysergamide and analogs at
      dopamine D1 and D2 receptors. Several of these compounds have been reported
      previously to bind with high affinity to serotonin 5HT2 (i.e., 3H-ketanserin)
      sites in the rat frontal cortex (K0.5 5-30 nM). All tested compounds also
      competed for both D1-like (3H-SCH 23390) and D2-like (3H-spiperone plus unlabeled
      ketanserin) DA receptors in rat striatum, with profiles indicative of agonists
      (nH < 1.0). The affinity of LSD and analogs for D2 like receptors was similar to
      their affinity for 5HT2 sites. The affinity for D1 like receptors was slightly
      lower (2- to 3-fold), although LSD and several analogs bound to D1 receptors with
      affinity similar to the prototypical D1 partial agonist SKF38393 (K0.5 ca. 25
      nM). A second series of experiments tested the binding and functional properties
      of LSD and selected analogs in C-6 glioma cells expressing the rhesus macaque D1A
      receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568622
TI  - Receptor binding profile suggests multiple mechanisms of action are responsible
      for ibogaine's putative anti-addictive activity.
AB  - The indole alkaloid ibogaine (NIH 10567, Endabuse) is currently being examined
      for its potential utility in the treatment of cocaine and opioid addiction.
      However, a clearly defined molecular mechanism of action for ibogaine's putative
      anti-addictive properties has not been delineated. Radioligand binding assays
      targeting over 50 distinct neurotransmitter receptors, ion channels, and select
      second messenger systems were employed to establish a broad in vitro
      pharmacological profile for ibogaine. These studies revealed that ibogaine
      interacted with a wide variety of receptors at concentrations of 1-100 microM.
      These included the mu, delta, kappa, opiate, 5HT2, 5HT3, and muscarinic1 and 2
      receptors, and the dopamine, norepinephrine, and serotonin uptake sites. In
      addition, ibogaine interacted with N-methyl-D-aspartic acid (NMDA) associated ion
      and sodium ion channels as determined by the inhibition of [3H]MK-801 and
      [3H]bactrachotoxin A 20-alpha-benzoate binding (BTX-B), respectively. This broad
      spectrum of activity may in part be responsible for ibogaine's putative anti
      addictive activity.

PMID- 7568628
TI  - Pharmacological specificity of delta 9-tetrahydrocannabinol discrimination in
      rats.
AB  - While many previous studies have shown that a variety of cannabinoids substitute
      and cross-substitute for delta 9-tetrahydrocannabinol (THC) in drug
      discrimination procedures, few have systematically examined potential THC-like
      effects of non-cannabinoid compounds. The purpose of the present study was to
      delineate further the pharmacological specificity of THC discrimination. Rats
      were trained to discriminate THC (3.0 mg/kg) from vehicle. Following
      determination of a dose-effect curve with THC, substitution tests with selected
      compounds from a variety of pharmacological classes, including l-phenylisopropyl
      adenosine, dizocilpine, dextromethorphan, clozapine, buspirone, MDL 72222,
      muscimol, midazolam and chlordiazepoxide, were performed. Whereas THC produced
      full dose-dependent substitution, substitution tests with non-cannabinoid drugs
      resulted in less than chance (50%) levels of responding on the THC-appropriate
      lever, with the exception of (+)-MDMA (2.5 mg/kg, 50%) and diazepam (3.0 mg/kg,
      67%). These results are consistent with those of previous studies and suggest
      that the discriminative stimulus effects of THC exhibit pharmacological
      specificity.

PMID- 7568629
TI  - Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence
      and evidence against alpha 2-adrenoceptor mediation.
AB  - The influence of alpha 2-adrenoceptor antagonists in animal models of anxiety is
      quite inconsistent, with results spanning the full range of effect from
      anxiogenesis to anxiolysis. In the present study, an ethological technique was
      used to examine the effects of yohimbine (0.5-4.0 mg/kg) on plus-maze behaviour
      in DBA/2 mice. Results indicated significant anxiolytic-like effects on standard
      spatiotemporal measures at 2.0-4.0 mg/kg, and on risk assessment measures across
      the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains
      confirmed that this action of yohimbine in the murine plus-maze is not peculiar
      to DBA/2 mice. The more selective alpha 2-adrenoceptor antagonist, idazoxan (0.63
      5.0 mg/kg), exerted much weaker behavioural effects in the maze while the alpha 2
      adrenoceptor agonist, clonidine (0.01-0.1 mg/kg), produced a profile consistent
      with non-specific behavioural disruption. Data are discussed in relation to the
      possible involvement of 5-HT1A receptor mechanisms in the observed anxiolytic
      like effects of yohimbine in the murine plus-maze.

PMID- 7568630
TI  - Bromocriptine enhancement of responding for conditioned reward depends on intact
      D1 receptor function.
AB  - It has been suggested that reward-related learning may require intact functioning
      at the dopamine D1 receptor. The present experiment tested this hypothesis by
      challenging the reward-enhancing effects of the D2 agonist, bromocriptine, with a
      D1 antagonist, SCH 23390. For comparison, the effects of the D2 antagonist,
      pimozide, were also evaluated. Male rats (n = 240) were pre-exposed to a chamber
      with two levers, one producing a 3-s lights-off stimulus and the other a 3-s tone
      stimulus. Four conditioning sessions followed, during which levers were absent
      and presentations of the lights-off stimulus were paired with food. Testing
      consisted of comparing presses on each lever after conditioning to before
      conditioning for each rat. Control groups showed a significantly greater increase
      in responding for lights-off than tone, indicating that the lights-off stimulus
      had become a conditioned reward. Results showed that bromocriptine (0.25-10.0
      mg/kg, IP, 60 min before test session) enhanced responding at doses of 2.5 and
      5.0 mg/kg significantly more on the conditioned reward lever than on the other
      lever. The lowest dose of SCH 23390 (1.0 microgram/kg, SC, 2 h before testing)
      eliminated the bromocriptine-produced enhancement at 2.5 mg/kg and a significant
      enhancement was seen at 10.0 mg/kg. The higher doses of SCH 23390 (5.0 and 10.0
      micrograms/kg) eliminated the bromocriptine effect and the conditioned reward
      effect itself, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568631
TI  - Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze.
AB  - The selective kappa agonist U-50,488H was evaluated on the elevated plus-maze
      test of anxiety. U-50,488H was administered intraperitoneally to male Sprague
      Dawley rats 20 min before testing, first in an open field apparatus, then
      followed immediately on the elevated plus-maze. No significant change in
      spontaneous locomotor activity was measured in the open field apparatus,
      suggesting that U-50,488H was devoid of sedative effects in the dose range tested
      (0.1-1000 micrograms/kg, IP). Doses between 10 and 1000 micrograms/kg produced
      significant increases in elevated plus-maze behavior that were consistent with
      anxiolytic actions for U-50,488H. These anxiolytic-like effects were antagonized
      by naloxone (2.0 mg/kg, IP), suggesting an opioid receptor site of action. In
      addition, we tested the kappa 1-selective U-50,488H-derivative, U-69,593 (100
      micrograms/kg, IP), which was also shown to mimic the anxiolytic-like effects
      produced by U-50,488H. These results suggest that low doses of the selective
      kappa 1 agonists U-50,488H and U-69,593 are endowed with anxiolytic properties in
      rodents and that the kappa opioid system may be involved in the behavioral
      response to anxiety.

PMID- 7568633
TI  - Alcohol pharmacodynamics in young-elderly adults contrasted with young and middle
      aged subjects.
AB  - Effects of aging on ethyl alcohol (EtOH) pharmacodynamics were examined over
      progressive dosing schedules (0.4, 0.6, 0.8, 1.0 g/kg) in groups of young (25.0
      +/- 2.9 years), middle-aged (41.1 +/- 6.6 years), and young-elderly adults (60.9
      +/- 2.6 years) using three computerized cognitive-neuromotor tasks: digit-symbol
      substitution (DSS), keypad reaction time (KRT), and subcritical tracking (SCT).
      Hysteresis curves of performance impairment (adjusted for pre-drug baseline) as a
      function of blood alcohol concentration (BAC) were examined for time-course
      effects, and regression analyses were performed to assess the contribution of age
      beyond that accounted for by BAC. Results reflected differences in the patterning
      but not magnitude of impairment for elderly subjects, with earlier decrements and
      more rapid acute tolerance observed for DSS, in conjunction with less
      pharmacodynamic sensitivity for SCT. Regression analyses furthermore indicated
      that age and impairment were negatively related, arguing against synergistic
      intoxication effects as a function of aging. Analyses specifically comparing
      performance at baseline versus legally intoxicating BACs (> 1.0 mg/ml) likewise
      reflected a lack of interactive effects involving the elderly. Elderly subjects
      nevertheless exhibited significantly lower baseline performance for DSS and KRT
      than young subjects and achieved higher BACs with equivalent doses. These latter
      findings support the exercise of caution by elderly individuals consuming EtOH
      prior to engaging in neuromotor pursuits such as driving.

PMID- 7568632
TI  - Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in
      MPTP-lesioned monkeys.
AB  - Interactions at the behavioral level between dopamine (DA) and opioid receptors
      in the mammalian brain have been amply demonstrated. Considering the pivotal role
      for DA receptors in the pharmacotherapy of Parkinson's disease (PD), these
      interactions might be clinically relevant. Therefore, in the present study the
      effects of the opioid antagonist naltrexone and agonist morphine on D1 and D2
      receptor induced stimulation of motor behavior in the unilateral MPTP monkey
      model (n = 5) of PD were investigated. The results show that both naltrexone and
      morphine [0.1-1.0 mg/kg; intramuscular injection (IM)] inhibited D2 receptor
      stimulated contralateral rotational behavior and hand use induced by
      administration of quinpirole (LY 171555; 0.01 mg/kg, IM) in a dose-related way.
      However, no effects of these opioid drugs were observed on D1 receptor stimulated
      contralateral rotational behavior and hand use induced by administration of SKF
      81297 (0.3 mg/kg, IM). Interestingly, the action of the alleged preferential mu
      receptor antagonist naltrexone was mimicked by the selective delta-opioid
      antagonist naltrindole (0.5 mg/kg, IM). From this study it is concluded that in a
      non-human primate model of PD, alteration of opioid tonus leads to modulation of
      D2 receptor but not D1 receptor controlled motor behavior. The possible
      underlying mechanisms and clinical relevance of these findings are discussed.

PMID- 7568635
TI  - Time course of the effects of diazepam and lorazepam on perceptual priming and
      explicit memory.
AB  - The effects of diazepam and lorazepam on explicit memory and perceptual priming
      were studied 50, 130 and 300 min after drug administration. Sixty healthy
      volunteers were randomly assigned to one of five parallel groups (placebo,
      diazepam 0.2 or 0.3 mg/kg, lorazepam 0.026 or 0.038 mg/kg). The corresponding
      doses of benzodiazepines exerted a similar negative effect on explicit
      performance. Lorazepam markedly impaired priming performance, whereas the effect
      of diazepam was intermediate between that of placebo and that of lorazepam 0.038
      mg/kg. The impairment was maximal at the theoretical peak plasma concentration.
      Contamination by explicit memory could account for the decrease in priming
      performance observed in the diazepam groups.

PMID- 7568634
TI  - Effect of pindolol on the prolactin response to d-fenfluramine.
AB  - We studied the effect of the 5-HT1A receptor antagonist, pindolol, on the
      prolactin (PRL) response to the 5-HT releasing agent, d-fenfluramine (d-FEN), in
      ten healthy male volunteers. Pindolol pretreatment lowered baseline PRL levels
      but, when this effect was taken into account, did not significantly attenuate the
      PRL response to d-FEN. Within the limitations that attend the use of pindolol as
      a 5-HT1A receptor antagonist, the data suggest that although 5-HT1A receptors may
      play a role in the tonic release of PRL, they are not involved in the release of
      PRL produced by d-FEN. We propose that the PRL response to d-FEN may involve
      selective activation of postsynaptic 5-HT2 receptors.

PMID- 7568636
TI  - Effects of anger/hostility, defensiveness, gender, and family history of
      hypertension on cardiovascular reactivity.
AB  - In this study, we examined the combined effects of anger/hostility and
      defensiveness on reactivity to three stressors (math, handgrip, cold pressor) and
      how these effects are moderated by gender and family history of hypertension. The
      subjects were 209 college students. Low compared with high Spielberger anger-out
      scores were associated with greater diastolic blood pressure (DBP) reactivity in
      low- but not high-defensive women with a negative family history. High compared
      with low hostility scores were associated with greater heart rate reactivity in
      low-defensive men with an opposite effect in high-defensive men. Gender, family
      history, and defensiveness each affected differential DBP reactivity to the three
      tasks. Combined study of biological factors and coping styles can improve our
      understanding of cardiovascular reactivity and disease.

PMID- 7568637
TI  - Psychophysiological responses as indices of affective dimensions.
AB  - The startle reflex, facial electromyogram (EMG), and autonomic nervous system
      responses were examined during imagery varying in affective valence and arousal.
      Subjects (N = 48) imagined affective situations during tone-cued 8-s trials.
      Startle blink magnitudes were larger and latencies faster during negatively
      valent than during positively valent conditions and during high-arousal than
      during low-arousal conditions. Greatest heart rate acceleration and fastest and
      largest skin conductance responses to startle probes occurred during high-arousal
      imagery. Zygomatic and orbicularis oculi facial muscle activities were higher
      during high-arousal imagery, whereas corrugator muscle activity was higher during
      low-arousal imagery. Zygomatic and corrugator activity also varied with emotional
      valence. The startle and facial EMG responses are most parsimoniously organized
      by the negative affect (NA) and positive affect (PA) dimensions, respectively.
      This NA/PA framework integrates previous research, dimensional theories of
      emotional behavior, and physiological assessment of pathological emotion.

PMID- 7568638
TI  - Determinants of subjective experience of sexual arousal in women: feedback from
      genital arousal and erotic stimulus content.
AB  - Sixty-two women participated in a study designed to explore the association
      between genital and subjective sexual arousal. Four stimulus conditions were
      created, designed to evoke differential patterns of genital arousal over time.
      Subjects were instructed to report sensations in their genitalia while being
      exposed to the same erotic stimulus on repeated trials or to a series of varying
      erotic stimuli. Detection of genital arousal was facilitated by the occurrence of
      changes in genital arousal over trials. That is, genital and subjective sexual
      arousal were linearly related in conditions that resulted in large differences in
      genital arousal over trials, whereas such a relation was absent in conditions in
      which genital arousal levels remained relatively constant. In women, peripheral
      feedback from consciously detected genital arousal seems to be a relatively
      unimportant determinant of subjective sexual arousal.

PMID- 7568639
TI  - Consistency of heart rate and sympathovagal reactivity across different autonomic
      contexts.
AB  - Theories that psychophysiological reactivity constitutes a risk factor for
      coronary artery disease assume that reactivity is a consistent individual
      characteristic. We tested this assumption by measuring reactivity to three
      psychologically challenging tasks performed by 22 healthy subjects across
      different autonomic contexts produced by positional change. Dependent variables
      included heart rate (HR), low-frequency (LF; 0.04-0.15 Hz) and high-frequency
      (HF; 0.15-0.50 Hz) heart period variability, and the LF/HF ratio. HR (r = .44, p
      < .05) and LF/HF ratio (r = .48, p = .03) reactivity were modestly correlated
      across the different autonomic contexts, but HF and LF power reactivity were not.
      These findings suggest that HR reactivity to psychological challenge is a
      modestly consistent characteristic of individuals, despite differences in
      autonomic context. Although the same is true of cardiac sympathovagal balance,
      reactivity of HF and LF power were less consistent.

PMID- 7568640
TI  - Effects of sound intensity on a midlatency evoked response to repeated auditory
      stimuli in schizophrenic and normal subjects.
AB  - Inhibitory gating of response to repeated stimuli is demonstrated by several
      event-related potentials, including the auditory P50 wave. The present study
      examined the effects of variation in sound intensity on this phenomenon in
      schizophrenics and normal subjects. Paired clicks, 500 ms apart, were presented
      50 dB above threshold to 10 normal subjects and 10 schizophrenics. The normal
      subjects demonstrated significantly more decrement of response to the second
      stimulus than did the schizophrenics. When the sounds were noticeably louder(70
      dB above threshold), no such difference was observed. Rather, both groups had
      similarly diminished gating of response. A significant difference between
      schizophrenics and normal subjects was also observed when the sounds were 30 dB
      above threshold, but the difference was smaller than that at 50 dB. At any
      stimulus intensity, concomitant eye movements led to loss of gating of P50 in the
      normal subjects.

PMID- 7568641
TI  - P300 hemispheric amplitude asymmetries from a visual oddball task.
AB  - The P3(00) event-related potential (ERP) was elicited in 80 normal, right-handed
      male subjects using a simple visual discrimination task, with
      electroencephalographic (EEG) activity recorded at 19 electrodes. P3 amplitude
      was larger over the right than over the left hemisphere electrode sites primarily
      at anteromedial locations (F3/4, C3/4) for target, novel, and standard stimuli.
      The N1, P2, and N2 components also demonstrated hemispheric asymmetries. The
      strongest P3 hemispheric asymmetries for all stimuli were observed at anterior
      locations, suggesting a frontal right hemisphere localization for initial
      stimulus processing, although target stimuli produced larger P3 amplitudes at
      parietal locations that did novel stimuli. The relationships of hemispheric
      asymmetries to anatomical variables, background EEG activity, and neurocognitive
      factors are discussed.

PMID- 7568642
TI  - Assessment of female sexual arousal: response specificity and construct validity.
AB  - Specificity of vaginal pulse amplitude and vaginal blood volume in reaction to
      visual sexual stimuli was investigated by comparing responses to sexual, anxiety
      inducing, sexually threatening, and neutral film excerpts. Subjective sexual
      arousal, body sensations, emotional experience, skin conductance, and heart rate
      were monitored along with the genital measures. Self-report data confirmed the
      generation of affective states as intended. Results demonstrated response
      specificity of vaginal vasocongestion to sexual stimuli. In terms of both
      convergent and divergent validity, vaginal pulse amplitude was the superior
      genital measure. Skin conductance discriminated among stimuli only to a small
      degree, whereas heart rate failed to discriminate among stimuli altogether.

PMID- 7568643
TI  - Dimensional analysis of resting human EEG. II: Surrogate-data testing indicates
      nonlinearity but not low-dimensional chaos.
AB  - Surrogate-data testing has recently been proposed as one way to detect the
      presence of nonlinearity and low-dimensional chaos in experimental time series.
      Such testing involves estimating correlation dimension for both the original data
      and surrogate data from which nonlinearity has been removed. We applied such
      testing to the same resting, eyes-closed, and eyes-open electroencephalogram
      (EEG) data set that was originally analyzed using dimension estimation applied
      only to the original data (Pritchard & Duke, 1992). Two kinds of surrogate-data
      sets had higher estimated dimension and poorer saturation. This indicates that
      the normal resting human EEG is nonlinear and therefore not a linear-stochastic
      system. Because nearly complete saturation at some loci was not differently
      affected by the surrogate-data procedures, our results also indicate that the
      normal resting human EEG is high dimensional and does not represent low
      dimensional chaos.

PMID- 7568645
TI  - Shades of gray matter: noninvasive optical images of human brain responses during
      visual stimulation.
AB  - Recent theories about human brain function emphasize the need for imaging methods
      that allow the study of dynamic interactions among different structures. In this
      paper, we report on a new technique, based on the measurement of parameters of
      migration of near-infrared photons, that yields functional images of the human
      occipital cortex, combining a spatial resolution of 0.5 cm and a temporal
      resolution of 50 ms. This technique appears to be suitable for studying the
      dynamics of cortical activation.

PMID- 7568644
TI  - Time and frequency domain methods for heart rate variability analysis: a
      methodological comparison.
AB  - The purpose of this paper is to analytically evaluate and compare two of the most
      common methods for measuring respiration-related heart rate fluctuations: linear
      detrended heart rate power spectral analysis and the Porges technique of filtered
      variance. Low-frequency power was removed from instantaneous 4-Hz R-R interval
      signals using either a first-order linear (linear/spectral technique) or a third
      order polynomial (MPF-var technique). The signals were band-pass filtered and
      analyzed in both the time and frequency domains. Although in most cases the two
      techniques yielded substantially similar results, the MPF-var technique resulted
      in signal amplification at a few specific frequencies. The frequency range and
      effect to amplification of the MPF-var technique were dependent upon the
      polynomial size, sampling frequency, and frequency content of the signal.

PMID- 7568646
TI  - [Dream interpretation as access to the unconscious?--An experimental
      psychological evaluation].
AB  - An experiment was carried out to test Freud's assumption that the elements of the
      manifest dream are in particular closeness to the repressed unconscious and that
      free associations starting from them should therefore encounter quickly
      successively growing resistance. 30 female subjects were asked to associate to
      parts of their own dreams and of those of a control subject. Skin conductance
      reactions (SCR) were assessed during these procedures. The areas below the SCR
      curves, considered as a measure for psychophysiological activation, were
      significantly greater during associations to own dreams. In addition, SCR values
      rose significantly more often in the course of associations to the persons' own
      dreams than to those of other subjects. The correlation between subjectively
      perceived emotionality and integrated SCR values proved to be high. This
      justifies the use of the variable as an indicator of affective arousal. Although
      the experimental condition was necessarily only a rather incomplete realisation
      of the psychoanalytic situation, our results clearly support Freud's theory.

PMID- 7568648
TI  - [Is the psyche antiquated? A typology of psychotherapeutic critique of
      civilization in the works of Alexander Mitscherlich].
AB  - In the oeuvre of the psychotherapist Alexander Mitscherlich, one of the founding
      fathers of psychosomatic medicine in post-war Germany, three basic types of
      critique of civilization can be identified. They each imply a specific conception
      of the relation between modernity and psychological disorder. Mitscherlich's
      ideas on the topic have evolved in a manner consistent with his appropriation of
      psychoanalysis and his confrontation with the causes and consequences of human
      behaviour during the time of national socialism.

PMID- 7568647
TI  - [Magnetism and immorality--or the rapid demise of magnetism in Berlin around 1819
      1820].
AB  - In the years 1821 and 1822 two books offered contradictory accounts of a scandal
      in Berlin involving sexual abuse in connection with magnetism. Historical
      research has determined that the accused was the famous physician and magnetizer
      Karl Christian Wolfart. If, however, we look more closely at the general context,
      it appears that this was not just a case of abuse of the therapeutic
      relationship. Rather, it is suggested that a specific combination of therapeutic
      ignorance and particular psycho-social influences contributed almost inevitably
      to the abuse of patients--sexually or otherwise.

PMID- 7568649
TI  - [Education in psychosomatic medicine/psychotherapy at German universities: a
      critical evaluation of the current status].
AB  - The integration of psychosomatics/psychotherapy into the medical curriculum has
      not yet resolved the majority of problems in conveying a bio-psycho-social
      perspective to medical students. A survey, conducted 1992/93 at the university
      departments of psychosomatics-psychotherapy in Germany yielded that there is no
      true integration of a bio-psycho-social perspective into the curriculum up until
      now. A second investigation with students of the university of Ulm in 1993
      revealed that there is substantial variety in the quality of teaching and that
      improvement is possible with resources already available. Consequences with
      regard to changes to be expected by the 8th renewal of the present teaching
      regulations ("Approbationsordnung") are discussed. A pilot project aiming at the
      integration of preclinical and clinical aspects of the psychosocial aspects of
      medicine is outlined.

PMID- 7568651
TI  - The pediatric medical-psychiatric unit in a psychiatric hospital.
AB  - Interest in the development of pediatric medical-psychiatric units continues to
      grow, driven by clinical, financial, and interdisciplinary considerations. While
      virtually all of the pediatric medical-psychiatric units reported in the
      literature to date have arisen in the pediatric setting, there are considerations
      that may encourage the development of such programs in the psychiatric setting.
      The authors report on the development and characteristics of a pediatric medical
      psychiatric specialty inpatient unit developed in a psychiatric hospital.
      Advantages and disadvantages of the psychiatric hospital setting are considered
      in light of cumulative experience.

PMID- 7568650
TI  - The future of organ transplant psychiatry.
AB  - The future of organ transplant psychiatry depends less on immunologic and
      surgical advances than on 1) an increased supply of donor organs, 2) more
      sophisticated multicenter outcome studies, and 3) understanding of the subjective
      as well as objective aspects of compliance and quality of life for transplant
      recipients. From future studies, we may improve the selection process for
      candidates and discover which approaches are optimal for anxiety, depressive,
      organic mental, and personality disorders. Absolute contraindications to
      transplantation may become relative. Integration of ethical concerns with
      biomedical and psychosocial criteria for selection will challenge future
      investigators given the inadequate supply of donor organs.

PMID- 7568652
TI  - Patient requests for euthanasia and assisted suicide in terminal illness. The
      role of the psychiatrist.
AB  - Psychosocial assessment and treatment are critical elements of care for
      terminally ill patients who desire hastened death. Most patients, in saying that
      they want to die, are asking for assistance in living--for help in dealing with
      depression, anxiety about the future, grief, lack of control, dependence,
      physical suffering, and spiritual despair. In this article, the authors review
      current understandings of the psychiatric aspects of requests by terminally ill
      patients for assisted suicide and euthanasia; describe an approach to the common
      problems of physical, psychological, social, and spiritual suffering encountered
      in managing dying patients; and elaborate the functions of the psychiatrist in
      addressing these problems.

PMID- 7568655
TI  - Delirium presenting with symptoms of depression.
AB  - This study was designed to determine if symptoms of delirium were mistaken for
      symptoms of depression in hospitalized patients referred for psychiatric
      consultation. Records were surveyed for all patients seen by a university
      hospital psychiatric consultation-liaison service for a 38-month period. Of 737
      patients referred for depressive symptoms, 42 received a final diagnosis of
      delirium. Those patients with delirium tended to be older and were more likely to
      be male when compared with all patients referred for symptoms of depression.
      Given the grave prognostic implications of delayed or missed diagnosis, one needs
      to be aware that the presentation of delirium may be disguised as depression.

PMID- 7568654
TI  - Enhancing the health of somatization disorder patients. Effectiveness of short
      term group therapy.
AB  - To identify an effective method of treating patients with somatization disorder
      (SD), the authors conducted a randomized controlled clinical trial of group
      therapy with 70 SD patients. Primary care physicians treating all patients in the
      study received a consultation letter offering treatment recommendations for SD.
      The experimental patients were invited to attend eight group therapy sessions in
      addition to the consultation provided to their physicians; 45% attended one or
      more sessions. The experimental patients reported significantly better physical
      (P < 0.05) and mental (P < 0.01) health in a 1-year period during and after group
      therapy. The more group sessions SD patients attended, the greater the
      improvement in general and mental health. The 52% net savings in health care
      charges associated with group therapy plus the consultation indicate that it is
      economically feasible to improve outcomes without escalating the cost of care in
      this group of high users of medical resources.

PMID- 7568656
TI  - Increasing identification and referral of panic disorder over the past decade.
AB  - The study's objective was to contrast the prevalence, phenomenology, and medical
      care utilization for panic disorder from 1980 to 1990. All psychiatric
      consultations from a university consultation service from the years 1980, 1985,
      and 1990 were located (N = 2,400). Patients meeting DSM-III-R panic disorder
      criteria were selected for chart review. Variations in demographics, comorbidity,
      prior medical evaluations, and referral patterns were analyzed. The prevalence
      rate for consultations meeting panic disorder criteria has increased (2.5% in
      1980, 4.2% in 1985, and 5.1% in 1990; chi 2 = 7.5, P = 0.024). Referring
      physicians more frequently noted panic attacks in 1990 (5% in 1980, 21% in 1985,
      and 59% in 1990; chi 2 = 21.2, P = 0.0001). A summary measure of medical care
      utilization revealed no significant interval change. Panic disorder is being
      recognized and referred more frequently by medical physicians since the
      publication of DSM-III and DSM-III-R. However, delay of diagnosis and high
      medical care utilization remain significant problems.

PMID- 7568653
TI  - Rating scales for the psychosocial evaluation of organ transplant candidates.
      Comparison of the PACT and TERS with bone marrow transplant patients.
AB  - Two scaled formats for summarizing the results of psychosocial evaluations of
      transplant candidates have been published, the Psychosocial Assessment of
      Candidates for Transplantation (PACT) and the Transplant Evaluation Rating Scale
      (TERS). In this study, 40 consecutive candidates for bone marrow transplant were
      rated on the PACT and TERS. The PACT and TERS were comparable in interrater
      reliability. Similar conceptual items for each scale correlated fairly highly
      with one another. The PACT and TERS differ in several scale characteristics. The
      authors discuss the relationship between scale characteristics and clinical
      utility.

PMID- 7568657
TI  - Pseudoseizures after epilepsy surgery.
AB  - Seizure surgery for medically intractable partial epilepsy in selected patients
      usually results in dramatically improved seizure control. However, the authors
      present six patients who, after surgery for refractory complex partial seizures,
      postoperatively experienced pseudoseizures (also known as nonepileptic seizures),
      confirmed with EEG monitoring. Three of these patients also had nonepileptic
      seizures preoperatively that coexisted with their partial epilepsy. Psychiatric
      assessment revealed that this patient group had several characteristics in
      common, which suggests that preoperative psychiatric consultation may help
      identify those patients at risk for developing nonepileptic seizures. Treatment
      strategies with anticonvulsant medications and behavioral therapy are reviewed.

PMID- 7568658
TI  - Psychosocial effects of enhanced external counterpulsation in the angina patient.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive pantaloon device
      designed to increase coronary artery flow in the treatment of angina. This pilot
      study, conducted in 1992-1993, which used psychosocial testing pre- and
      posttreatment, yielded data suggesting that EECP is well tolerated psychosocially
      and produces improvement in the anginal syndrome. More comprehensive research is
      under way to test these preliminary conclusions.

PMID- 7568660
TI  - Cupid's arrow. An unusual presentation of factitious disorder.

PMID- 7568659
TI  - Panic disorder and complex partial seizures. A truly complex relationship.

PMID- 7568661
TI  - Mania secondary to lisinopril therapy.

PMID- 7568662
TI  - Factitious disorders and fraud.

PMID- 7568665
TI  - A belief in nurse practitioners.

PMID- 7568663
TI  - Nurses critical to patient well-being: unlicensed staff should not perform
      nursing duties.

PMID- 7568664
TI  - Giving yourself permission to have breathing space.

PMID- 7568666
TI  - Are you committing strategic resume errors that can sabotage your job-search
      campaign?

PMID- 7568668
TI  - How to handle (D) evaluations (i.e. what to do about poor evaluations).

PMID- 7568667
TI  - The breathing space report. Roasting the sacred cows of time management.

PMID- 7568669
TI  - Nursing in the '90s. Is home care nursing right for you?

PMID- 7568670
TI  - Was it really wrongful termination?

PMID- 7568671
TI  - Healthcare changes bring increased liability risk for nurses.

PMID- 7568672
TI  - Nurse practitioners: myths and misconceptions.

PMID- 7568673
TI  - Concerted evolution of repetitive DNA sequences in eukaryotes.
AB  - A large fraction, sometimes the largest fraction, of a eukaryotic genome consists
      of repeated DNA sequences. Copy numbers range from several thousand to millions
      per diploid genome. All classes of repetitive DNA sequences examined to date
      exhibit apparently general, but little studied, patterns of "concerted
      evolution." Historically, concerted evolution has been defined as the
      nonindependent evolution of repetitive DNA sequences, resulting in a sequence
      similarity of repeating units that is greater within than among species. This
      intraspecific homogenization of repetitive sequence arrays is said to take place
      via the poorly understood mechanisms of "molecular drive." The evolutionary
      population dynamics of molecular drive remains largely unstudied in natural
      populations, and thus the potential significance of these evolutionary dynamics
      for population differentiation is unknown. This review attempts to demonstrate
      the potential importance of the mechanisms responsible for concerted evolution in
      the differentiation of populations. It contends that any natural grouping that is
      characterized by reproductive isolation and limited gene flow is capable of
      exhibiting concerted evolution of repetitive DNA arrays. Such effects are known
      to occur in protein and RNA-coding repetitive sequences, as well as in so-called
      "junk DNA," and thus have important implications for the differentiation and
      discrimination of natural populations.

PMID- 7568674
TI  - Diffuse scattering in protein crystallography.

PMID- 7568675
TI  - The potential and limitations of neutrons, electrons and X-rays for atomic
      resolution microscopy of unstained biological molecules.
AB  - Radiation damage is the main problem which prevents the determination of the
      structure of a single biological macromolecule at atomic resolution using any
      kind of microscopy. This is true whether neutrons, electrons or X-rays are used
      as the illumination. For neutrons, the cross-section for nuclear capture and the
      associated energy deposition and radiation damage could be reduced by using
      samples that are fully deuterated and 15N-labelled and by using fast neutrons,
      but single molecule biological microscopy is still not feasible. For naturally
      occurring biological material, electrons at present provide the most information
      for a given amount of radiation damage. Using phase contrast electron microscopy
      on biological molecules and macromolecular assemblies of approximately 10(5)
      molecular weight and above, there is in theory enough information present in the
      image to allow determination of the position and orientation of individual
      particles: the application of averaging methods can then be used to provide an
      atomic resolution structure. The images of approximately 10,000 particles are
      required. Below 10(5) molecular weight, some kind of crystal or other
      geometrically ordered aggregate is necessary to provide a sufficiently high
      combined molecular weight to allow for the alignment. In practice, the present
      quality of the best images still falls short of that attainable in theory and
      this means that a greater number of particles must be averaged and that the
      molecular weight limitation is somewhat larger than the predicted limit. For X
      rays, the amount of damage per useful elastic scattering event is several hundred
      times greater than for electrons at all wavelengths and energies and therefore
      the requirements on specimen size and number of particles are correspondingly
      larger. Because of the lack of sufficiently bright neutron sources in the
      foreseeable future, electron microscopy in practice provides the greatest
      potential for immediate progress.

PMID- 7568677
TI  - The fissure sealant impasse.

PMID- 7568676
TI  - Progress in high resolution atomic force microscopy in biology.

PMID- 7568679
TI  - Esthetic considerations in the construction of a removable partial denture.
AB  - In the construction of a removable partial denture, the patient's interest
      frequently lies in the improvement of his or her esthetic appearance. This desire
      can be underestimated by the scientifically trained dentist, resulting in a
      disappointed patient. The perimeters of potential esthetic improvement might be
      influenced by the limitations of each individual case. However, appropriate care
      in the selection, arrangement, and position of teeth can overcome some of the
      limitations. This article describes the benefits of a well-planned, systematic
      approach to selection of the framework design, porcelain shade, and tooth mold as
      well as the base finish, and it illustrates, with specific examples, how to
      achieve the maximum esthetics in removable partial denture prosthodontics.

PMID- 7568678
TI  - Influence of acid type (phosphoric or maleic) on the retention of pit and fissure
      sealant: an in vivo study.
AB  - Two hundred twenty permanent young molars in 60 children aged 8 to 13 years
      received only one application of a light-activated resinous sealant. The
      retention rate was assessed 6 and 12 months later. The teeth were divided into 2
      groups of 110 each. In one of the groups the pits and fissures were etched with
      37% phosphoric acid before being sealed (group 1); in the other (group 2) these
      areas were etched with 10% maleic acid. The retention rate of group 1 was 98.4%
      at 6 months, and 96.8% at 12 months. Group 2 had retention rates of 97.5% at 6
      months and 95% at 12 months. There was no statistically significant difference
      between the two groups in the two test periods, nor were there differences in the
      same group at the different periods.

PMID- 7568680
TI  - Check records--a chairside mounting procedure.
AB  - This article considers the logistical problems involved when the check
      (interocclusal) record procedure is used to remount complete dentures on an
      articulator. It reports the development of upper and lower "check record mounting
      blocks" that may be made to fit any articulator, thus enabling the procedure to
      be performed easily and quickly at chairside.

PMID- 7568681
TI  - Effect of surface-penetrating sealant on wear resistance of luting agents.
AB  - The wear of composite resin is influenced by the presence of microcracks on its
      surface. Recently, it has been shown that surface-penetrating sealants are
      effective in reducing the wear of posterior composite resin by sealing these
      defects. The purpose of this study was to investigate the effects of one of these
      sealants on the wear of various luting agents in conjunction with composite resin
      inlays. The specimens were subjected to a three-body wear test for 400,000
      cycles. The wear values of both composite resin and luting agents were determined
      by profilometric tracings to the nearest 2 microns. There were no statistically
      significant differences between the treated and untreated groups as it related to
      the wear of the luting agents. The wear values of composite resin inlays treated
      with the sealant, however, were significantly lower than those without treatment,
      regardless of the type of luting agent used for cementation.

PMID- 7568682
TI  - Where is the gap? Machinable ceramic systems and conventional laboratory
      restorations at a glance.
AB  - Scanning electron microscopy was used to compare the marginal gaps of
      restorations milled by machinable ceramic systems to the marginal gaps of
      conventional laboratory-sintered ceramic restorations. For occlusal surfaces, the
      average marginal gap was 80 microns for both laboratory- and Celay-produced
      inlays. The mean gap was 200 microns and 170 microns, respectively, for Cerec T
      (turbine motor) and Cerec EM (electric motor) inlays. For approximal boxes, the
      average marginal gap was 100 microns for inlays produced with conventional
      laboratory-sintering techniques, 80 microns for Celay restorations, and 280
      microns for the Cerec T restorations, and 260 microns for Cerec EM-machined
      inlays. The ceramics used, as well as the different systems themselves, can
      influence the results and the clinical outcome of the restorations.

PMID- 7568683
TI  - Reducing microleakage in Class II restorations: an in vitro study.
AB  - The aim of this in vitro study was to evaluate four methods of reducing the
      marginal microleakage of directly placed Class II composite resin restorations.
      Mesio-occlusal and disto-occlusal preparations with all margins confined to
      enamel were placed in extracted human molars. The teeth were restored with one of
      four techniques using multi-incremental placement, stored for 24 hours in 37
      degrees C water, thermocycled, and placed in a dye solution. The teeth were
      sectioned in a mesiodistal direction through the restoration and evaluated for
      microleakage at the gingival margins. Restorations placed in conjunction with an
      enamel bonding agent demonstrated severe microleakage. Marginal microleakage was
      reduced by the use of an extended base of visible light-cured glass-ionomer
      cement, a BondAband, or a dentinal bonding agent.

PMID- 7568684
TI  - Removal of latex glove contaminants prior to taking poly (vinylsiloxane)
      impressions.
AB  - Sulfur compounds found in latex gloves may be deposited on teeth and gingiva,
      inhibiting the setting of poly(vinylsiloxane) impression materials. The objective
      of this in vivo study was to screen a variety of methods to remove these
      contaminants. Ten patients were each tested with eight decontamination methods.
      Before each trial, the facial surfaces and adjacent gingiva of the maxillary
      central and lateral incisors were contaminated with 20 wipes of a latex glove.
      Decontamination methods included a 30-second rinse with mouthwash, 3% hydrogen
      peroxide, or air-water syringe; a 30-second toothbrush scrub with water,
      mouthwash, or hydrogen peroxide; a 30-second cotton pellet-Cavidry scrub; and a
      30-second cleaning with a prophy cup and pumice. A 10-second water rinse followed
      each method except the air-water syringe and Cavidry groups. A low-viscosity
      poly(vinylsiloxane) impression material was then used to take an impression of
      the area. To test surface inhibition, the gingival, tooth, and palatal impression
      surfaces were wiped with cotton-tipped applicators, and the degree of inhibition
      was subjectively categorized by two independent investigators. Mechanical
      decontamination with a toothbrush or pumice was significantly more effective than
      was rinsing alone, regardless of the solution used.

PMID- 7568686
TI  - The effect of acid-etched dentin on marginal seal.
AB  - Treatment of dentin with acids results in a surface change that is potentially
      useful for mechanical retention of resins in tooth structure. This study examined
      the effect of etching of dentin on the seal of cavities restored with composite
      resin. Eighty cavities, each measuring 2.0 mm in diameter and 1.5 mm in depth,
      were prepared in dentin of extracted human teeth and randomly assigned to two
      equal groups. The experimental group was etched with 37% phosphoric acid for 15
      seconds before restoration. The control specimens were similarly restored but
      without any etching of dentin. After the specimens were thermocycled, the seal of
      each cavity was assessed by measurement of the gap between the restorative
      material and the tooth structure. The experimental group registered significantly
      better adaptation to the cavities than did the control group.

PMID- 7568685
TI  - Bond strengths of dentinal bonding systems to enamel and dentin.
AB  - Contemporary, third-generation dentinal bonding products have become highly
      specialized in producing high bond strengths to dentin. This investigation
      compared in vitro bond strengths of six dentinal bonding systems and their
      matched composite resins to human enamel and dentin. The effects of treatment by
      dentinal primers on enamel bond strengths as well as the effects of phosphoric
      acid on the strengths of dentinal bonds were measured. The use of dentinal primer
      on enamel improved the bond strengths of Prisma Universal Bond 3/Prisma APH and
      XR Bond/Herculite systems and had no effect on Denthesive/Charisma, Scotchbond
      2/Silux, and Tenure/Perfection, while the enamel bond strengths of Gluma/Pekalux
      declined. Pretreatment of dentin with phosphoric acid improved the bond strengths
      of Denthesive/Charisma, Prisma Universal Bond 3/Prisma APH and XR Bond/Herculite,
      but had no effect on Gluma/Pekalux, Scotchbond 2/Silux and Tenure/Perfection.

PMID- 7568687
TI  - The responsibility is yours.

PMID- 7568688
TI  - Tooth bleaching for children and teens: a protocol and examples.
AB  - Even though there has been much interest in dental bleaching in recent years,
      little has been reported about patient-applied carbamide peroxide tooth bleaching
      for children and adolescents. This technique article describes "at home" tooth
      bleaching for young patients and offers a proven protocol for the procedure.
      Representative cases are documented with pretreatment and posttreatment
      photographs. Bleaching in conjunction with enamel microabrasion is also reviewed.

PMID- 7568689
TI  - Change in pH of plaque and 10% carbamide peroxide solution during nightguard
      vital bleaching treatment.
AB  - The purpose of this study was to evaluate in vivo changes in the pH of plaque and
      of a 10% carbamide peroxide solution occurring within the bleaching guard during
      a 2-hour nightguard vital bleaching procedure. Baseline pH values for plaque and
      the carbamide peroxide solution were established. A small hole was placed in the
      anterior interproximal region of the guard to allow placement of the pH
      electrode. The pH of the carbamide peroxide solution was measured at 5-minute
      intervals. After 2 hours, the guard was removed and pH of the plaque was
      remeasured. The procedure was repeated three times on each of four subjects. The
      mean baseline pH reading for plaque was 6.31 and mean final pH reading was 6.86.
      The difference was statistically significant. At initial placement of the
      carbamide peroxide-filled guard, the mean intraguard pH was 4.50 (range of 2.80
      to 7.80). The mean peak intraguard pH of 8.06 (range of 7.30 to 8.43), which was
      significantly different from baseline, was obtained within 31 minutes. The pH of
      plaque, saliva, and a 10% carbamide peroxide bleaching solution within the guard
      increased significantly during bleaching and remained significantly elevated for
      the duration of the study (2 hours).

PMID- 7568690
TI  - Implant-retained mandibular overdentures: a simplified, cost-effective treatment
      approach.
AB  - The use of implant-retained complete overdentures is a viable treatment modality
      in compromised patients. Use of two separate implants in the mandible enhances
      the retention and stability of the denture, which is still mainly supported by
      soft tissues. A technique for clinical fixation of the internal attachment to a
      laboratory-rebased and tissue-loaded mandibular overdenture is described. The
      advantages, disadvantages, and the rationale of the treatment are presented.

PMID- 7568691
TI  - Evaluation of an adhesive system for amalgam repair: bond strength and porosity.
AB  - This study compared the shear bond strengths and the porosity at the bond sites
      of a spherical amalgam alloy to those of an admixed amalgam alloy, when they were
      bonded to like and unlike alloy specimens with or without a resin bonding
      material. The spherical alloy had higher bond strength and less porosity than did
      the admixed alloy, whether bonded to spherical or admixed alloy. The results
      suggest that use of a spherical alloy should be strongly considered when an
      amalgam restoration is to be repaired with an amalgam alloy, regardless of the
      type of alloy used in the original restoration. Use of a resin bonding agent did
      not increase bond strengths of amalgam to amalgam.

PMID- 7568692
TI  - Clinical and laboratory techniques for repair of fractured porcelain in fixed
      prostheses: a case report.
AB  - A technique used to repair the abutment tooth of a fixed partial metal-ceramic
      prosthesis is described. This prosthesis extended from the maxillary central
      incisor to the left canine. The whole porcelain facial aspect of the central
      incisor had been fractured. Following a reduction of the metallic structure, a
      single porcelain crown was bonded to that area. The repair was quick, less
      expensive and less difficult than removal of the prosthesis and fabrication of a
      replacement, and provided excellent esthetic and functional results.

PMID- 7568693
TI  - Epidermolysis bullosa: a case report.
AB  - The term epidermolysis bullosa describes a group of rare genetic mechanicobullous
      disorders. The disease has several modes of inheritance with various degrees of
      severity and expression. A patient with simplex epidermolysis bullosa had typical
      cutaneous lesions and dental involvement. The teeth were severely affected by
      hypoplasia. Dental therapy consisted of placement of amalgam restorations and
      topical applications of fluoride. The need for, and advantages of, early
      preventive and restorative dental care are illustrated by the case presented.

PMID- 7568694
TI  - Effect of incision and flap reflection on postoperative pain after the removal of
      partially impacted mandibular third molars.
AB  - A clinical trial was carried out to evaluate the influence of incision and
      reflection of a flap on pain after the removal of partially erupted mandibular
      third molars. A sequential design for intraindividual comparisons was chosen. The
      patients underwent bilateral extraction of partially impacted mandibular third
      molars with a standard incision on one side (control) and without incision (test)
      on the other side. One week postoperatively, the patients were asked on which
      side they had experienced more postoperative pain. The preset level of
      significance (P < .05) was reached after 11 patients were treated. Eight patients
      had more severe pain on the control side, while three patients did not experience
      any difference in pain between the two sides. The nonsurgical approach did not
      increase the chair time and appeared to be an effective way of reducing
      postoperative discomfort after extraction of partially erupted third molars.

PMID- 7568697
TI  - Questionable coauthorship--an erosion of ethical standards.

PMID- 7568695
TI  - The effects of current dentinal adhesives on the dentinal surface.
AB  - The effects of the dentinal surface treatments from six currently available
      commercial dentinal adhesives are presented. The adhesives are All-Bond 2, etched
      and unetched, Syntac, Prisma Universal Bond 3, Scotchbond Multipurpose, Tenure
      Solution, and Adhesive By Choice. Unerupted third molar human teeth were
      sectioned and treated with the appropriate adhesive according to the
      manufacturer's directions. After the teeth were treated, they were processed for
      observation by scanning electron microscopy. Scanning-electron microscopic
      photomicrographs were made of each step in the process to show the effects of the
      constituents, including the adhesives, on the dentinal surface. For All-Bond 2,
      unetched, the smear layer was not removed before the primer and the adhesive were
      applied. The primer for Prisma Universal Bond 3 altered the smear layer by
      reacting with it but did not produce a large demineralized zone in the dentin.
      All the other adhesives did remove the smear layer before the tooth was treated
      with the primer and adhesive.

PMID- 7568696
TI  - Micromorphologic relationship between resin and dentin in Class II restorations:
      an in vivo and in vitro investigation by scanning electron microscopy.
AB  - The wetting property of dentinal bonding systems may play an important role in
      the mechanism of adhesion to dentin. Some studies have observed that tags
      penetrate 100 microns or more in nonvital teeth and less than 10 microns in vital
      teeth. This investigation was designed to evaluate the micromorphologic
      relationship between in vivo and in vitro dentin after application of two new
      dentinal bonding systems in Class II restorations. Class II cavities were
      restored in vitro and in vivo with Gluma 2000 adhesive and Pekafill hybrid resin
      or Scotchbond Multi-purpose adhesive and Z100 composite resin. After dissolution
      of dental structures, the restorations were observed with a scanning electron
      microscope. No morphologic differences were found between in vivo and in vitro
      specimens with either of the new dentinal adhesive systems tested. Short resin
      tags were often found in vivo, particularly at the cavity walls. Only a few areas
      in vivo had deep resin tags (longer than 100 microns) and these were always at
      the cavity floor.

PMID- 7568698
TI  - Intraoral metal adhesion utilized for occlusal rehabilitation.
AB  - Recent advances in adhesive monomers and surface preparation methods allow strong
      resin adhesion to all intraoral metal surfaces. Resin-metal bond strengths may
      exceed typical resin-etched enamel bonds. Innovations in prosthetic procedures
      have resulted. Data for metal adhesion are reviewed and the use of intraoral
      metal adhesion to finalize an occlusal rehabilitation is illustrated. Included in
      the metal surface preparations are intraoral sandblasting and intraoral tin
      plating.

PMID- 7568699
TI  - A simplified technique for prosthetic treatment of microstomia in a patient with
      scleroderma: a case report.
AB  - A simplified technique was used to treat a patient who had limited mouth opening
      as a result of scleroderma. Treatment included the construction of a three-piece,
      sectional maxillary partial denture and a one-piece mandibular complete denture.

PMID- 7568700
TI  - Complete-crown and partial-coverage tooth preparation designs for bonded cast
      ceramic restorations.
AB  - A new concept for tooth preparation design for complete- and partial-coverage all
      ceramic restorations is presented. Because of the efficacy of third-generation
      dentinal bonding agents, the preparations for complete-coverage and partial
      coverage restorations can be made with less emphasis on retentive form. For
      partial-coverage restorations, cavosurface angles should be large so that the
      resultant configuration of the enamel rods is conducive to optimal bonding. The
      new preparations are simple, with extremely tapered axial walls, to allow maximum
      thickness of the ceramic material. These types of preparations result in finished
      restorations that are stronger and have better margins and less chance of
      microleakage. Long-term success of these types of restorations will be determined
      by the success or failure of the dentinal bonding agent and resin cement system
      used.

PMID- 7568702
TI  - Salivary pH changes during 10% carbamide peroxide bleaching.
AB  - The purpose of this study was to evaluate the effect on salivary pH of a 10%
      carbamide peroxide solution when used with a custom-fitted guard for bleaching
      teeth. Baseline pH values were established for unstimulated saliva and on saliva
      produced while wearing an empty guard. After insertion of a guard half filled
      with Proxigel, salivary pH measurements were made at 5-minute intervals until the
      values returned to baseline levels. Mean salivary pH values were 6.81 +/- 0.11
      for unstimulated samples and 6.91 +/- 0.18 after insertion of the empty guard.
      After insertion of the filled guard, there was a statistically insignificant
      decrease in salivary pH during the first 5 minutes, followed by an increase above
      baseline at 10 minutes, to a mean peak value of 7.32 +/- 0.27 at 15 minutes. The
      difference between the baseline values and the mean peak value at 15 minutes was
      statistically significant. The results of the study indicated that the pH of
      saliva increased significantly during the first 15 minutes of nightguard vital
      bleaching and did not significantly drop below baseline in the first 2 hours
      after insertion with a moderately low-pH solution.

PMID- 7568701
TI  - Home-use tooth bleaching agents: an in vitro study on quantitative effects on
      enamel, dentin, and cementum.
AB  - Studies on home-use bleaching agents containing carbamide or hydrogen peroxide
      demonstrate minimal topographic alteration and insignificant organic change to
      tooth material. This in vitro study evaluated the effects of a three-step
      commercial home-use bleaching agent on extracted human incisors over time. Each
      tooth was digitized by baseline and sequential profilometry and analyzed using
      computer software. Statistically significant volume loss was evident in cementum
      and dentin after simulations of 4 and 8 weeks of use.

PMID- 7568704
TI  - Contiguous autogenous transplant--nineteen years' clinical and radiographic
      follow-up: a case report.
AB  - Contiguous autogenous transplant, also known as the bone-swaging procedure, is a
      technique aimed at regenerating lost periodontium. Clinical healing of bony
      defects after bone swaging has been satisfactory, but the relationship and mode
      of attachment between the bone graft and the root surface have not been fully
      investigated. A 19-year clinical and radiographic follow-up of a bony defect
      treated with the bone-swaging technique is presented. A significant coronal
      increase in bone height and a gain in clinical probing depth were achieved
      postsurgery and remained unchanged during the first 6 years. The long-term
      clinical and radiographic findings, however, indicated that the attachment
      developed at the root-bone interface may not have been a true attachment and may
      have been more vulnerable to pathogenic local agents. These observations may help
      the clinician to interpret the clinical and radiographic changes that occur in
      the area of a bony defect following the use of a bone graft.

PMID- 7568703
TI  - Congenital erythropoietic porphyria--oral manifestations and dental treatment in
      childhood: a case report.
AB  - Congenital erythropoietic porphyria is a rare condition resulting from an inborn
      error in prophyrin metabolism. This deficiency leads to hemolytic anemia,
      photosensitivity, blistering of the skin, and deposition of red-brown pigments in
      the bones and teeth. The literature regarding the dental aspects of this disorder
      is briefly reviewed and the preventive, restorative, and esthetic dental
      management of a 4-year-old child with congenital erythropoietic porphyria is
      described.

PMID- 7568705
TI  - In vivo wear ranking of some restorative materials.
AB  - An in vivo experiment to determine the wear of restorative materials (gold,
      ceramic, and microfilled resin) was performed in a patient with bruxism.
      Telescopic crowns were placed on teeth 35, 36, and 37. The opposing surfaces were
      all made from ceramic material. The weight loss of the materials was recorded
      after 30, 60, and 90 days and converted to volume loss. Replicas for scanning
      electron microscopic studies were obtained. Gold and ceramic material wore
      equally, while the wear of microfilled resin was two and a half times as much.
      The ceramic material and the microfilled resin chipped and fractured, but the
      gold did not. Mainly abrasive and fatigue types of wear were found in all
      materials.

PMID- 7568707
TI  - Microleakage of composite resin restorations with various etching times.
AB  - Microleakage was assessed in Class V composite resin restorations, placed in
      extracted noncarious human premolar teeth after the enamel cavosurface margins of
      the preparations had been etched with phosphoric acid for 5, 15, or 30 seconds.
      The restored teeth were thermocycled, placed in methylene blue dye, invested, and
      sectioned. The extent of dye penetration along the tooth-restoration interface in
      the three etching groups was compared. The group etched for 5 seconds showed the
      greatest leakage; leakage was statistically significantly greater than that in
      the groups etched for 15 or 30 seconds. The tooth-restoration interface at the
      occlusal and gingival margins showed more leakage than did the mesial or distal
      margins.

PMID- 7568706
TI  - Clinical evaluation of resin-bonded prostheses: Rochette technique.
AB  - Ninety patients, with a total of 90 resin-bonded prostheses placed in a private
      dental office from 1981 to 1991, were recalled for clinical evaluation of their
      restorations. Tissue condition, patient satisfaction, prosthesis failures by
      location and by sex of patient were assessed. Debondings occurred in both the
      mandibular and maxillary arches. In the present study, there were no gender-based
      differences in the rate of debonding and prostheses with more than two retainers
      were more likely to have problems.

PMID- 7568709
TI  - Proposed nomenclature for glass-ionomer dental cements and related materials.

PMID- 7568708
TI  - Composite resin-amalgam compound restorations.
AB  - Extensive silver amalgam restorations in premolars and molars occasionally
      require sacrifice of healthy unsupported enamel walls or cusps. A posterior
      composite resin-amalgam compound technique has been proposed to conserve these
      structures. Microleakage was high at the enamel-amalgam interface, moderate at
      the composite resin-silver amalgam and dentin-composite resin interfaces, and
      minimal between the inner enamel and the composite resin. Light microscopy and
      scanning electron microscopy demonstrated that marginal adaptation of the silver
      amalgam to the composite resin of the cusps was acceptable and that penetration
      of the inner etched enamel to the composite resin was complete.

PMID- 7568711
TI  - Effectiveness of reflective wedges on the polymerization of composite resins.
AB  - Polymerization of three composite resins was evaluated after they were light
      cured through one of four different reflective wedges. Other experimental
      variables were activation times and light units used. The same conditions were
      used for a control group, in which photoactivation was performed directly on the
      test specimens. Complete polymerization was never achieved when the curing light
      was directed through reflective wedges.

PMID- 7568710
TI  - Increase in residual crest bone using guided tissue regeneration: a clinical case
      report.
AB  - A case is described in which delayed implants were inserted after the creation of
      a suitable volume of maxillary crest bone. The procedure used osseointegrated
      implants, expanded polytetrafluoroethylene membranes, and demineralized bone.

PMID- 7568713
TI  - Fabrication of an implant surgical guide using a denture replica technique.
AB  - The outcome of the prosthodontic phase of implant treatment is affected by the
      position of implant fixtures within the dental supporting tissues; therefore,
      surgical guides are often used to facilitate ideal fixture placement. This
      article describes the fabrication and modification of a wax replica of the
      patient's existing prosthesis, which is converted into a surgical guide. This
      approach permits accurate fixture placement relative to planned tooth positions
      in the implant-supported prosthesis, without the need to fabricate a new
      conventional denture prior to surgery.

PMID- 7568712
TI  - A comparison of fluoride release from four glass-ionomer cements.
AB  - Fluoride release from three glass-ionomer cements and one cement was measured
      over 1 year and compared. All the materials released fluoride in a similar
      pattern for the study's duration: The fluoride release was greatest on the first
      day, decreased sharply the second day, and gradually diminished. After 1 year,
      all specimens released daily fluoride concentrations above 0.5 ppm, reaching as
      much as 7 ppm. Low powder-liquid ratios always lead to more fluoride release than
      high ratios.

PMID- 7568714
TI  - Reproducibility of occlusal contacts relative to mounting cast variables.
AB  - This study evaluated the accuracy of occlusal contacts relative to the mode in
      which casts are mounted. Specifically, the direct effect on occlusal contacts was
      assessed with respect to: (a) the type of mounting stone used; (b) the amount of
      material used relative to the distance between the mounting plate and the cast
      base; and (c) the presence or absence of a restriction of the articulator's
      vertical opening. A 3 x 2 x 2 factorial analysis of variance and a Dunn's
      Multiple Comparison Procedure (P < .05) showed that one of the three mounting
      stones was statistically significantly less accurate in reproducing occlusal
      contacts when a distance of 19 mm existed between the cast and the articulator,
      regardless of the existance of articulator restriction.

PMID- 7568715
TI  - The micromorphologic relationship between resin and dentin in Class V
      restorations: an in vivo and in vitro investigation.
AB  - Recently several new bonding agents that show promising in vitro performance have
      been marketed. Frequently there is inconsistency between in vitro test results
      and in vivo performance of new adhesive materials. This investigation was
      designed to evaluate the micromorphologic relationship between in vivo and in
      vitro dentin after application of two new dentinal bonding systems. V-shaped
      cavities were restored in vitro and in vivo with Gluma 2000 bonding system and
      Pekafill composite resin and Scotchbond Multi-Purpose bonding system and Z100
      composite resin. After dissolution of dental structures, the restorations were
      observed with scanning electron microscope. No morphologic differences were found
      between in vivo and in vitro specimens of either dentinal adhesive system.
      Intertubular and peritubular dentin was reproduced accurately in every specimen.

PMID- 7568717
TI  - Long- and short-term space maintenance following the uprighting of molars: a case
      report.
AB  - The technique of using a light-hardened glass-ionomer-resin cement restorative
      material and a stainless steel round wire as a long-term retentive space
      maintainer following the uprighting of mandibular molars is introduced through
      the report of a clinical case. The technique is modified for incorporation into
      provisional acrylic resin restorations as a short-term retentive space maintainer
      in the time interval between the impression and the cementation of the fixed
      partial denture.

PMID- 7568716
TI  - In vivo and in vitro analysis of a bonding agent.
AB  - Recently many researchers have become interested in the adhesion of composite
      resin to the dentinal surface. Because it is easier to obtain good composite
      resin adhesion when a surface is free from smear plug, several chemical agents
      (acids or linking agents) have been suggested for surface preparation.
      Nevertheless, the pretreatment of dentin leads to an increase of pulpal outflow,
      which can interfere with the bonding agent's adhesion. Thus, new-generation
      dentinal bonding agents appeared on the market. They use a pool of highly
      absorbent primers to facilitate the scattering of the agent in the dentin
      substratum under humid conditions. The present study shows the results, obtained
      with the help of scanning electron microscopy, of resinous penetration into the
      tubular structures of dentin using a latest-generation bonding system. The in
      vivo and in vitro tests showed a deep scattering of intermediate fluid resin into
      tubules, even in the presence of physiologic outflow of dentinal fluids.

PMID- 7568718
TI  - Dentists troubled by the administration of anesthetic injections: long-term
      stresses and effects.
AB  - A questionnaire was mailed to 3,000 practicing dentists to inquire about their
      physical and psychological responses to the task of administering local
      anesthesia. Surprisingly, 18.8% of the 711 responding dentists reported that the
      administration of injections causes them enough distress to have (at least at
      some time) reconsidered dentistry as a career. Six percent of respondents
      considered their thoughts and feelings to be a serious problem, whereas only 2%
      reported no negative reactions to this aspect of clinical practice. Self-reported
      reactions to various anesthetic procedures were compared, and the various
      responses are discussed. It is concluded that the administration of anesthetic
      injections is a rarely discussed but significant contributor to the overall
      professional stress and difficulty for many, but not all, dentists.

PMID- 7568719
TI  - Influence of dental glove type on the penetration of liquid through experimental
      perforation: a spectrophotometric analysis.
AB  - This study was made to assess whether the physical structure or the commercial
      make of a glove has any influence on the penetration of liquid through
      perforations in the glove during work. A comparison was made between three types
      of gloves (10 for each brand name and type): vinyl (Peha Fit, Paul Hartmann),
      latex (without ASTM certification), and Biogel D (Regent Dental Division) for a
      total of 30 gloves. Of the 10 gloves for each type, five were worn tightly
      adhering to the operator's hand and five were worn relatively loosely. Holes of a
      predetermined size (0.40 mm) were made in each glove on the index, middle, and
      ring fingers, for a total of 90 holes. A randomized preprogrammed list ensured a
      perfect balance of the three variables: type of glove, adherence to the hand, and
      fingers having holes. The amount of liquid that penetrated the gloves through the
      holes was determined by placing the gloved hand in a tank containing a colored
      substance for 3 minutes and then analyzing the colored substance that had
      penetrated the glove with an ultraviolet (UV) spectrophotometer. The results
      clearly showed that the amount of liquid that penetrated through the holes varied
      significantly (p < 0.001) according to the type of glove tested. The mean
      quantity of liquid penetrating the vinyl gloves (6.24 microL) was approximately
      five times higher than that of the latex gloves (1.20 microL), and 100 times
      higher than that of the Biogel D gloves (0.05 microL). The statistical
      differences between the three types of gloves were even more significant in the
      cases in which the glove adhered closely to the hand (12.44 microL in vinyl, 2.37
      microL in latex, and 0.09 microL in Biogel D), whereas no significant difference
      was found when the gloves were loose (0.03 microL in vinyl, 0.04 microL in latex,
      and 0.00 microL in Biogel D).

PMID- 7568721
TI  - Talon cusp--clinical significance and management: case reports.
AB  - Talon cusp is a rare dental anomaly manifested as an accessory cusplike structure
      on the tooth crown. This article reports four cases of talon cusp that caused
      clinical problems related to appearance, occlusal interference, tooth
      displacement, caries, and tongue irritation. The cases presented were associated
      with other dental abnormalities, suggesting per se that genetic inheritance may
      be the causative factor. Clinical and radiographic characteristics of this
      developmental anomaly and modes of treatment are described.

PMID- 7568720
TI  - Fabrication of an implant radiologic-surgical stent for the partially edentulous
      patient.
AB  - This article describes a technique for fabrication of an implant radiologic
      surgical stent, made of thermocurable clear resin, for the partially edentulous
      patient. Dual-curing composite resin is mixed with colored chalk powder and
      incorporated into the stent to provide contrast during computerized tomographic
      bone evaluation and to serve as an easily visible guide during fixture placement.

PMID- 7568722
TI  - Lateral-access Class II restoration using resin-modified glass-ionomer or silver
      cermet cement.
AB  - Direct-access preparation of a carious proximal surface is perhaps the most
      conservative approach to restoration. Physical properties and handling
      characteristics of silver amalgam and of resin composite and lack of fluoride ion
      release make these materials unsuitable for direct buccal- or lingual-access
      proximal restoration. Insufficient strengths and radiolucency of self-hardening
      glass-ionomer cements preclude their use for Class II restorations. However,
      glass-ionomer silver-cermet cement and some resin-modified glass-ionomer
      materials are proving useful for non-stress-bearing Class II restorations and may
      have applications in preventive dentistry. This article describes lateral-access
      Class II restoration with modified glass-ionomer cements. Emphasis is placed on
      careful handling of materials, maintenance of an ideal operative field, and
      conservation of tooth structure.

PMID- 7568723
TI  - Marginal adaptation and seal of direct and indirect Class II composite resin
      restorations: an in vitro evaluation.
AB  - The aim of this in vitro study was to evaluate the marginal adaptation and seal
      of posterior composite resin restorations made with direct (three-sited
      multilayering) or indirect (extraoral inlay) techniques. The influence on the
      marginal quality of the cervical finishing design (butt or beveled) and residual
      enamel height (0.5, 1.0, and 1.5 mm up to the cementoenamel junction) was also
      evaluated. This trial was performed on sound, freshly extracted human molars.
      When residual enamel was less than 1.0 mm in height or 0.5 mm in thickness,
      indirect restoration resulted in superior marginal quality. For preparations with
      sufficient residual enamel height (greater than 1.0 mm), beveling of gingival
      margins appeared mandatory for good adaptation of direct restorations and
      beneficial to the adaptation of indirect restorations. Residual gingival enamel
      height and thickness demonstrated an influence on marginal quality only in
      indirect restorations with butt margins.

PMID- 7568724
TI  - Scanning electron micrographic effects of air-abrasion cavity preparation on
      human enamel and dentin.
AB  - Recent developments in technology and restorative materials have renewed interest
      in air abrasion as a means of tooth preparation. The technique, also called
      kinetic cavity preparation, uses kinetic energy to remove tooth structure. The
      purpose of this investigation was to use scanning electron microscopy to compare
      the effects of this technique to those of high-speed burs on extracted human
      teeth. Class V buccal preparations were made on five teeth with a No. 34 carbide
      bur used at 400,000 rpm and on 23 teeth with kinetic cavity preparation using
      differing combinations of aluminum oxide particle sizes and delivery pressures.
      Features of the specimens prepared at high speed included sharp line angles,
      chipping of the cavo-surface margin, and striated internal surfaces. Kinetic
      cavity preparations had rounded cavo-surface margins and internal line angles.
      The surfaces were microscopically rough and the dentinal tubules were occluded.
      There was little difference in appearance between specimens treated with various
      combinations of particle sizes and delivery pressures.

PMID- 7568726
TI  - Investigation into the genesis of angular lesions at the cervical region of
      teeth.
AB  - A review of the literature concerning the genesis of angular lesions of the teeth
      implicates occlusal stress as a critical component in the multifactorial etiology
      of these lesions. Clinical suggestions for the prevention and treatment of such
      defects are proposed.

PMID- 7568725
TI  - Comparisons of fit of CAD-CAM restorations using three imaging surfaces.
AB  - One of the factors that influences the overall fit of a Cerec restoration is the
      thickness of the optical powder. The objective of this study was to compare the
      measurement of the fit of glass inlays produced with the Cerec instrument after
      each preparation had been coated, in separate trials, with imaging powder applied
      with an aerosol; imaging powder applied with air from a dental unit; and a water
      soluble paint applied with a brush. Ten inlay preparations were made in extracted
      teeth. Each preparation was coated with one of the three imaging media and an
      inlay was made. This was repeated until each preparation received each imaging
      surface. Each inlay was measured at eight different points by using an image
      analysis system interfaced to a stereoscopic measuring microscope. The inlays
      fabricated on the two powder surfaces were not significantly different, but the
      painted surfaces were found to result in a significantly better-fitting inlay.

PMID- 7568727
TI  - Team management of atrophic edentulism with autogenous inlay, veneer, and split
      grafts and endosseous implants: case reports.
AB  - Predictable success of autogenous graft and implant reconstructions is critically
      dependent on preoperative alignment and prosthetic considerations planned by the
      surgeon and the restorative dentist in a team approach. In such cases the surgeon
      has an opportunity to place accurate bone grafts that allow implants to be
      secured in both the correct position and correct axis for good prosthetic
      restoration. With careful thought, the restorative dentist and surgeon can plan
      the location, shape, and volume of an implant-graft reconstruction. Nine
      requirements for successful onlay grating with implants and five case reports
      illustrating the team approach are presented.

PMID- 7568728
TI  - Bonding to enamel and dentin: a brief history and state of the art, 1995.
AB  - The acid-etch technique for bonding composite resins to enamel has revolutionized
      the practice of restorative dentistry. The ability of clinicians to bond
      restorative materials to enamel has fundamentally changed such diverse areas as
      cavity preparation, caries prevention, and esthetic treatment options. Although
      bonding of resin to dentin has proved to be a difficult challenge, ongoing
      advances are improving the reliability and predictability of dentinal adhesion.
      The purpose of this article is to provide a brief history of enamel and dentinal
      bonding, as well as an overview of the current state of the art.

PMID- 7568729
TI  - Move over amalgam--at last.

PMID- 7568730
TI  - Treating ankylosed primary teeth in adult patients: a case report.
AB  - When ankylosed primary teeth are retained beyond the mixed-dentition stage and
      the involved teeth are below the occlusal plane, occlusal and interproximal
      contacts can be restored to esthetic and functional anatomic contours. With the
      development of new, improved posterior composite resins that have greater wear
      resistance and stronger adhesive bonding systems for enamel and dentin, new
      opportunities for conservative, simple, and efficient esthetic and functional
      restorations are possible in selected retained ankylosed primary molars.

PMID- 7568731
TI  - An alternative technique for recontouring cervical eroded and abraded areas: a
      case report.
AB  - This paper describes an adhesive technique to restore cervical erosion and
      abrasion lesions so that the area can be used for clasp retention of a removable
      partial denture. An enamel fragment is used to recontour the area, achieving
      function and esthetics.

PMID- 7568732
TI  - Removable partial denture abutment restoration: a case report illustrating a new
      direct technique.
AB  - The destruction of the crown underlying a partial denture can render useless an
      otherwise acceptable prosthesis unless some means can be found for building up
      the tooth under the prosthesis. The aim of this article is to introduce a
      technique in which light-curing glass-ionomer resin cement is utilized for the
      direct restoration of removable partial denture abutments. The cavity preparation
      is completed in the customary manner. The cement is applied en masse and covered
      with a suitable translucent separating sheet. The denture is reinserted and the
      restoration is light cured from the perimeter of the abutment. The denture is
      removed, and, with the aid of a suitable disclosing medium, the restoration is
      trimmed carefully to avoid reducing the intimate adaptation between the
      restoration and the removable partial denture. The technique is offered with full
      acknowledgement that it is a compromised treatment option.

PMID- 7568733
TI  - Oral rehabilitation of a patient with congenital partial anodontia using a
      rotational path removable partial denture: report of a case.
AB  - This case report describes the treatment of an adult patient with partial
      anodontia. Treatment began with the extraction of several retained primary teeth
      and the insertion of an immediate transitional removable partial denture that was
      used to evaluate the possibility of increasing the patient's vertical dimension
      of occlusion. Later, the entire mandibular arch was restored with fixed
      restorations. Once the vertical dimension of occlusion was established and
      controlled, the maxillary arch was restored. Metal-ceramic crowns placed on the
      central incisors were contoured to accommodate a rotational path removable
      partial denture. The partial denture utilized rigid metal retention on the distal
      surface of the central incisors instead of clasps. This design produced a very
      esthetic and stable prosthesis.

PMID- 7568734
TI  - Combination of conventional fixed partial dentures and a resin-bonded retainer
      with intraradicular retention and a semirigid connector: a case report.
AB  - A case of an anteriorly edentulous patient who was treated with a combination of
      traditional fixed dentures and a resin-bonded retainer with intraradicular
      retention joined by a nonrigid connector is presented. This type of treatment
      permits conservation of dental structure, favoring function and esthetic
      appearance.

PMID- 7568735
TI  - A method for assessing the damping characteristics of periodontal tissues: goals
      and limitations.
AB  - The Periotest method, an objective, noninvasive clinical diagnostic method, is a
      dynamic procedure that measures the resistance of the periodontium to a defined
      impact load. It has been reported that Periotest values depend to some extent on
      tooth mobility, but mainly on the damping characteristics of the periodontium.
      Nevertheless, the real clinical meaning of the measurements and some important
      limitations of the Periotest measuring principle still seem to be poorly
      understood. In the present study, the relationship between damping
      characteristics of periodontal tissues and tooth mobility was investigated. The
      best correlations between tooth deflection and Periotest values were found for
      teeth showing a certain degree of clinical mobility (R2 from .79 to .91).
      Nevertheless, this correlation was clearly lower when only healthy subjects were
      examined (R2 from .43 to .54). The better correlation found for forces greater
      than 1.0 N indicates that the damping characteristics assessed with the Periotest
      method are related to secondary tooth movement. The Periotest methodology,
      measuring principle, and limitations are critically reviewed.

PMID- 7568736
TI  - Clinical evaluation of plaque removal by counterrotational electric toothbrush in
      orthodontic patients.
AB  - In the present crossover clinical trial, the plaque-removing efficacy of a
      counterrotational toothbrush was compared to that of a normal toothbrush in
      orthodontic patients. Twenty subjects, aged 11 to 26 years, who had orthodontic
      brackets on all fully erupted teeth of at least one arch were selected. At the
      first appointment, a prophylaxis was given to bring the plaque score to 0. Ten
      subjects received counterrotational brushes, and 10 subjects received manual
      brushes according to a randomized list. At 14 days, plaque scores were recorded
      and another prophylaxis was given. The subjects who were using the electric brush
      were assigned to the manual brush and vice versa. At 28 days, plaque scores were
      reassessed. Results showed that the counterrotational brush was significantly
      more effective in removing supragingival plaque from bracketed teeth than was the
      manual brush. The differences in plaque-removing effectiveness were particularly
      consistent on the proximal surfaces of the teeth.

PMID- 7568738
TI  - Removal of an aspirated gold crown utilizing the laparoscopic biopsy forceps: a
      case report.
AB  - An aspirated gold crown could not be removed with standard instruments. The crown
      was successfully grasped and removed with a large biopsy forceps commonly used in
      the performance of laparoscopic cholecystectomy.

PMID- 7568737
TI  - Factors influencing the wearing of protective gloves in general dental practice.
AB  - The present study was undertaken to explore the factors that influence decisions
      regarding wearing of gloves in the setting of private general practice. A survey
      of 250 dentists in Brisbane, Australia (41% of the total private general
      practitioners in the region), was conducted. Routine use of gloves was
      commonplace (84.6%); however, many dentists experienced skin problems related to
      glove use. Years of experience and unsolicited patient comments regarding glove
      wearing were significantly associated with patterns of glove use, while other
      factors examined did not exert a significant effect (practice profile, practice
      location, frequency of treating patients known to have an infectious disease,
      rate of sharps injuries, choice of glove material, and frequency of adverse
      mucosal and cutaneous reactions). These results revealed the need for further
      educational campaigns in practical infection-control measures for all
      practitioners, regardless of their level of experience. An educational approach
      used by the authors is described.

PMID- 7568739
TI  - Occupational tooth abrasion in a dental technician: loss of tooth surface
      resulting from exposure to porcelain powder--a case report.
AB  - A dental technician suffered abrasion of his anterior teeth because of his
      technique of handling porcelain powder during the construction of restorations.
      To keep the brush moist, he habitually licked it as he applied porcelain powder
      to restorations. The porcelain powder, which is extremely abrasive, acted as a
      grinding powder between his maxillary and mandibular anterior teeth. Adjunctive
      orthodontics and a combination of adhesive, minimal-intervention restorations
      were used to create an esthetic and functional solution.

PMID- 7568741
TI  - Credit where credit is due.

PMID- 7568740
TI  - Effect of pulpal pressure on adhesion of resin composite to dentin: bovine serum
      versus saline.
AB  - The purpose of this study was to compare the tensile bond strengths of resin
      composite to dentin, mediated by two new bonding systems (Scotchbond Multi
      Purpose and Clearfil Liner Bond II), under simulated pulpal pressure when diluted
      bovine serum or saline was used as the pulpal fluid. The bond strengths of the
      two bonding systems to dentin (under a pulpal pressure of 15 cm of water)
      obtained when bovine serum was used were statistically significantly higher than
      those obtained when saline was used. These data suggest that the primers of these
      bonding systems decreased the dentinal permeability when the bovine serum pulpal
      fluid was used through the precipitation of serum proteins by the primers in the
      dentinal tubules. This may have allowed better penetration of the bonding resin
      monomers into the conditioned dentinal structure, thus improving the bond
      strength. These findings support the idea that topical application of dentinal
      bonding systems may be an effective therapy for treating hypersensitive dentin.

PMID- 7568742
TI  - Retention of teeth with reduced root length through use of a resin-bonded splint:
      a case report.
AB  - Orthodontic relapse and tooth migration are commonly observed in patients with
      severe postorthodontic root resorption. If conventional removable retention is
      not adequate, fixed splint retention is necessary. Proponents of flexible splints
      suggest that the difference in mobility between natural teeth and the rigid
      systems is responsible for the loss of cement seal in the rigid systems.
      Proponents of rigid splints suggest that the flexibility that allows physiologic
      movement of the teeth also contributes to fatigue and subsequent failure of the
      material in the flexible splint systems. A clinical technique for increasing
      retention, consequently improving the prognosis of a resin-bonded fixed splint,
      is described.

PMID- 7568743
TI  - Secondary retention of rubber dam: effective moisture control access
      considerations.
AB  - Primary rubber dam retention affects attachment of the latex sheet to the anchor
      teeth bordering the isolated working field. Secondary rubber dam retention is the
      provision of an effective seal at the dam-tooth junction, which is essential to
      the maintenance of adequate access and moisture control within the working field.
      Practical hints are offered to optimize access and moisture control through well
      planned and properly executed secondary retention of classic rubber dam
      applications. In addition, innovative solutions to the limitations of general
      field isolation, which pertain mostly to secondary retention of the unrestrained
      buccal and lingual curtains of the slit dam, are introduced.

PMID- 7568744
TI  - A reappraisal of indirect retention in removable partial dentures with long
      bilateral distal-extension saddles.
AB  - When only the six anterior teeth remain, it may appear that indirect retention
      cannot be achieved because the fulcrum line around which the denture may move
      when the distal extensions lift away from the mucosa is located behind the
      retentive tips of the clasps on the abutment teeth. This will be the case when
      the indirect retainer and the tips of the clasps are on the same level; however,
      if the tips of the clasps are nearer to the gingival margin than the indirect
      retainer, indirect retentive effects will be achieved.

PMID- 7568745
TI  - Marginal reservoirs for multiunit castings.
AB  - This study measured the distortion of one-piece base metal four-unit fixed
      partial dentures and recorded the effect of positioning "marginal reservoirs" on
      the wax patterns. Standard wax patterns were made in a special three-piece
      stainless steel mold. Twenty anterior prostheses were cast: 10 for the
      experimental group and 10 for the control group. The prostheses were cast in a
      nickel-chromium alloy and were measured with a traveling microscope with a
      micrometer scale. Premarked points were designated on gingivoaxial line angles
      for buccolingual and mesiodistal distances and diameters to record marginal
      discrepancies of specimens with or without marginal reservoirs. Castings with
      marginal reservoirs distorted significantly less than did the control fixed
      partial dentures.

PMID- 7568746
TI  - Immediate and indirect woven polyethylene ribbon--reinforced periodontal
      prosthetic splint: a case report.
AB  - The patient described in this case report required removal of several mandibular
      incisor teeth because of severe periodontal disease. She demanded an immediate
      replacement for these teeth, but, because of the periodontal conditions, it was
      not possible to use conventional approaches to fulfill her request. The decision
      was made to fabricate an immediate indirect-direct, reinforced, bonded composite
      resin periodontal prosthesis. The patient's extracted mandibular central incisors
      were used as pontic replacements. The procedure was expedient, inexpensive, and
      conservative, and the results were esthetic.

PMID- 7568747
TI  - Clinical evaluation of a new flossing device.
AB  - The clinical effectiveness of a new flossing device, the Floss Plus easy flosser,
      in reducing interproximal plaque and interproximal gingival inflammation was
      compared to the effectiveness of hand-held floss. The first phase studied 36
      dental students, while the second studied 26 adult patients undergoing supportive
      periodontal treatment. In both phases, the subjects were divided into two groups.
      One group used the flossing device, while the second group used hand-held floss.
      The Gingival Index and Plaque Index were taken at baseline, 1 week, and 6 weeks.
      All groups experienced a significant decrease in the amount of interproximal
      inflammation and plaque, regardless of which flossing method was used. There was
      no statistically significant difference between the two flossing methods in the
      reduction of interproximal inflammation or plaque. These results indicated that
      the Floss Plus easy flosser is as effective as hand-held floss in reducing
      interproximal plaque and gingivitis. The use of this aid may benefit those
      patients who lack the dexterity for hand-held floss or who find flossing
      cumbersome.

PMID- 7568748
TI  - Microscopic appearance of enamel white-spot lesions after acid etching.
AB  - Ultrastructural changes in surface characteristics of enamel white-spot lesions
      were compared with changes in the adjacent clinically sound enamel after they
      were etched with 30% phosphoric acid. Ten human permanent first molars exhibiting
      natural white-spot lesions were used as study specimens. The lesion surfaces and
      their adjacent sound enamel were etched with 30% phosphoric acid for 60 seconds.
      Specimens were then evaluated by polarized light microscopy, scanning electron
      microscopy, and energy-dispersive spectroscopy. The acid etching produced a
      porous surface on both the white-spot lesion and the surrounding sound enamel.
      However, the lesion surface appeared to be more resistant to acid and dissolved
      less than adjacent enamel. This difference in acid solubility produced a steplike
      appearance between a white-spot lesion and its adjacent enamel surface. Energy
      dispersive spectroscopy demonstrated no difference in relative calcium-phosphorus
      ratios among the acid-etched white-spot lesion, acid-etched sound enamel, and
      unetched sound enamel.

PMID- 7568749
TI  - Hypohidrotic ectodermal dysplasia: characteristics and treatment.
AB  - Hypohidrotic ectodermal dysplasia is a rare congenital disease that affects
      several ectodermal structures. The disease is usually transmitted as an X-linked
      recessive trait in which the gene is carried by the female and manifested in the
      male. Manifestations of the disease differ in severity and may involve teeth,
      skin, hair, nails, and sweat and sebaceous glands. Most affected children require
      extensive dental treatment to restore their appearance and help the development
      of a positive self-image.

PMID- 7568750
TI  - The effect of variations in bonding procedure on fracture resistance of dentin
      bonded all-ceramic crowns.
AB  - This in vitro study investigated the effect of dentinal bonding and ceramic
      etching procedures on the fracture resistance of all-ceramic crowns. These
      results were compared with the fracture resistance of similar crowns placed with
      a nonadhesive conventional cement. All results indicated that superior fracture
      resistance was obtained when dentinal bonding was incorporated into the luting
      procedure together with etching of the ceramic fitting surface and the use of
      resin-based luting material. The fracture resistance of specimens luted with such
      a procedure was significantly greater than that of specimens in which a
      conventional nonadhesive cement was used.

PMID- 7568751
TI  - AIDS and dental treatment--a freedom of choice issue.

PMID- 7568752
TI  - Case selection for porcelain veneers.
AB  - The options for correction of unesthetic teeth are numerous; among these
      treatments, porcelain veneers have received substantial attention from the
      profession and patients. The increase in dental health awareness and advances in
      dental materials and technology, such as the acid-etching technique, improved
      physical properties of composite luting resin, and the use of silane coupling
      agents, have contributed to the success ceramic veneers enjoy today. However, no
      single material or technique is without its limitations. This article therefore
      aims to review the criteria for case selection and the limitations of porcelain
      veneers in restorative dentistry.

PMID- 7568753
TI  - A customized acrylic resin shell for fabricating an amalgam core on the coronally
      debilitated, endodontically treated posterior tooth.
AB  - This article describes a technique for fabricating a custom acrylic resin shell
      that will ensure a properly designed amalgam core for the coronally debilitated,
      endodontically treated posterior tooth. A few simple procedures result in a core
      foundation for root protection, an ideal crown preparation, and a more
      predictable final restoration.

PMID- 7568755
TI  - Bacterial contamination of the water supply in newly installed dental units.
AB  - Bacterial contamination of the water supply of newly installed dental units was
      investigated. Water samples were collected from water supply lines to the dental
      operatories prior to connection of the dental units. Within hours following
      connection, and continuing for up to the 6 months of the study, water samples
      were obtained from the air-water syringe of the units. The samples were serially
      diluted 10-fold and plated on culture media for quantitative analysis. The
      formation of bacterial biofilm in the dental water supply tubing was monitored by
      scanning electron microscopy. The results of these studies revealed that the
      building's water supply to the dental units was contaminated prior to connection
      to the units. The water supply from the air-water syringe was therefore
      contaminated as well. The number of contaminant bacteria in the dental unit water
      supply increased for several weeks and then stabilized. The lumen of the dental
      tubing became progressively contaminated with bacterial biofilm, which
      subsequently became the primary reservoir for maintenance of the contamination of
      the dental unit water supply.

PMID- 7568754
TI  - A visual method of determining marginal placement of crowns: Part I. Marginal
      placement of anterior crowns.
AB  - The cervical margins of crowns are often placed subgingivally to satisfy
      patients' demands for esthetics, even though subgingival margins can adversely
      affect gingival health. Photographs of 527 Saudi citizens (285 men and 242 women)
      with natural and exaggerated smiles were recorded to determine if subgingival
      margins are always necessary. The photographs indicated that a substantial
      percentage of the participants did not display the gingival tissue of their
      anterior teeth during a natural smile. (Percentages ranged from 43.5% to 69.8% of
      maxillary teeth and from 93.7% to 97.9% of mandibular teeth). The percentage of
      subjects who did not reveal the gingival tissue of their maxillary anterior teeth
      during an exaggerated smile ranged from 22.7% to 39.3%; the percentage of
      mandibular anterior teeth ranged from 54.1% to 72.7%. There was no statistically
      significant difference between men and women regarding visibility of anterior
      teeth. Thus, a substantial number of these subjects could receive anterior crowns
      with supragingival margins without sacrificing esthetics.

PMID- 7568756
TI  - Oral findings in a child with Prader-Labhart-Willi syndrome.
AB  - This case report highlights the dental implications of some features of Prader
      Labhart-Willi syndrome. A 5-year-old child with this syndrome presented with a
      severe form of dental caries. The need for early dental consultation and
      preventive dental procedures is stressed.

PMID- 7568757
TI  - Supernumerary mesiodentes with familial character: a clinical report.
AB  - This article reports the occurrence of mesiodentes in three siblings. The
      etiology of this condition is discussed and genetic considerations, such as modes
      of inheritance and prevalence, are discussed.

PMID- 7568758
TI  - Conservative endodontic-restorative treatment for a severely damaged and
      periapically compromised molar: a case report.
AB  - Many teeth with apical involvement show apical external resorption, and become
      difficult to treat. A patient with a severely damaged, periapically compromised
      permanent molar was treated successfully with a combination of simple root canal
      therapy and a conventional amalgam restoration. This method offers an inexpensive
      and predictable alternative and provides the option for a different restorative
      approach in the future.

PMID- 7568759
TI  - Moisture susceptibility of resin-modified glass-ionomer materials.
AB  - The purposes of this experiment were to determine if resin-modified glass-ionomer
      cements are less sensitive to moisture than are conventional glass-ionomer
      cements, to investigate the effects of barrier coatings, and to study the effects
      of different setting environments. Discoid specimens of a variety of resin
      modified glass-ionomer materials and a conventional glass-ionomer cement control
      were stored in different environments and were protected with different barrier
      coatings. The diametral tensile strengths of the specimens were determined and
      analyzed with three-way analysis of variance. Resin-modified glass-ionomer
      cements are less sensitive to moisture than is the conventional glass-ionomer
      cement control. Drier environments produced stronger resin-modified glass-ionomer
      specimens. Use of a fissure sealant as a barrier coating increased overall
      specimen strength, and the individual materials differed in strength.

PMID- 7568760
TI  - Aglossia: a case report.
AB  - The case of a 30-year-old man with aglossia is reported. Aglossia, a rare
      condition, is a developmental disorder in which the entire tongue is absent. It
      is usually associated with jaw and facial anomalies. In this patient, both the
      maxilla and mandible were affected. Although the mortality rate of patients with
      aglossia is high, this patient has been able to cope with his oral function with
      minimal obstruction.

PMID- 7568761
TI  - Rise in pulp temperature during finishing and polishing of resin composite
      restorations: an in vitro study.
AB  - The aim of this study was to establish the effects of the working speed, the use
      of coolant, and the pressure applied on the temperature of the pulp when resin
      composite restorations are finished and polished. One hundred eighty teeth with
      resin composite restorations are finished and polished. One hundred eighty teeth
      with resin composite restorations were randomly distributed into groups to be
      finished and polished with violet, blue, or yellow flexible disks. Each group was
      randomly subdivided into six subgroups of 10 each. Four subgroups were finished
      and polished, without water cooling, under constant pressure at speeds of 10,000,
      8,000, 6,000 or 4,000 rpm. The other two subgroups were finished and polished at
      10,000 rpm, one without water cooling while work was carried out intermittently
      and the the other with water cooling while work was carried out constantly.
      Results implied that a maximal speed of 4,000 rpm should be applied when
      polishing is carried out continuously without water coolant. When water cooling
      is used, flexible disks can safely be used at a speed of 10,000 rpm and with
      continuous pressure.

PMID- 7568762
TI  - Modification of radiation-induced strand breaks by glutathione: comparison of
      single- and double-strand breaks in SV40 DNA.
AB  - A number of investigations have suggested that the widely observed oxygen
      enhancement of radiation-induced cell killing or intracellular DNA damage
      requires the presence of glutathione (GSH) or other thiols. We have adapted an in
      vitro model system to investigate the effects of GSH on radiation-induced DNA
      double-strand breaks (DSBs), lesions felt to be critical to cell death.
      Superhelical SV40 DNA, 25 micrograms/ml, was irradiated in air or nitrogen in the
      presence of 0-20 mM GSH and single-strand breaks (SSBs) and DSBs were measured
      using neutral gel electrophoresis/ethidium bromide fluorescence. Control
      experiments demonstrated that a substantial concentration of free SH was still
      present after irradiation. Dose-response curves for SSBs and DSBs in air or
      nitrogen were predominantly linear at all GSH concentrations tested from 0-20 mM,
      except for 20 mM GSH in nitrogen, indicating that both SSB and DSB formation are
      predominantly by one-hit mechanisms under these conditions. Dose-response curves
      for both SSBs and DSBs in nitrogen at 20 mM GSH closely tracked the corresponding
      linear curves in air for doses up to about 200 Gy, then reached a plateau at
      higher doses. Induction efficiencies in 20 mM GSH, calculated from these initial
      slopes for both SSBs and DSBs in nitrogen, were unexpectedly higher than the
      corresponding efficiencies in 5 mM GSH, suggesting additional damage, rather than
      the expected additional protection. The possible mechanism for a damaging effect
      from GSH is discussed. Oxygen enhancement ratios (OERs) were calculated from the
      slopes of dose-response curves. The OERs for SSBs did not differ substantially
      from those for DSBs at the same [GSH], contrary to the observations of Prise et
      al. (Radiat. Res. 134, 102-106, 1993). The OERs for SSBs and DSBs peaked at 6.5
      and 8, respectively, at 5 mM GSH. These similarities suggest that the much lower
      OERs (2.5-3.0) generally reported for radiation killing of cells, which also
      typically contain about 5 mM GSH, cannot be accounted for by differences in OER
      between lethal lesions, represented by DSBs, and nonlethal lesions, represented
      by SSBs. In view of the present results, another possible explanation, that
      intracellular compounds other than reduced thiols are important in the chemical
      modification of the response of DNA to radiation, seems to be much more likely.

PMID- 7568763
TI  - Reduced temperature (22 degrees C) results in enhancement of cell killing and
      neoplastic transformation in noncycling HeLa x skin fibroblast human hybrid cells
      irradiated with low-dose-rate gamma radiation.
AB  - The effect of reduced temperature (22 degrees C) or serum deprivation during low
      dose-rate (0.66 cGy/min) gamma irradiation on cell killing and neoplastic
      transformation has been examined using the HeLa x skin fibroblast human hybrid
      cell system. The reduced temperature stops progression of these cells through the
      cell cycle while serum deprivation slows down cell turnover markedly. The data
      demonstrate an enhancement in both of the end points when cells are held at 22
      degrees C compared to parallel experiments done at 37 degrees C. In operational
      terms, the decreased survival and increased neoplastic transformation are
      consistent with our earlier hypothesis of a higher probability of misrepair at
      reduced temperature (Redpath et al., Radiat. Res. 137, 323-329, 1994). The
      interpretation that this damage enhancement was associated with the reduced
      temperature, and not the fact that the cells were noncycling, was supported by
      the results of experiments performed with cells cultured at 37 degrees C in serum
      free medium for 35 h prior to and then during the 12.24 h low-dose-rate radiation
      exposure. Under these conditions, cell cycle progression, as shown by reduction
      in growth rate and dual-parameter flow cytometric analysis, was considerably
      inhibited (cell cycle time increased from 20 h to 40 h), and there was no
      significant enhancement of cell killing or neoplastic transformation.

PMID- 7568766
TI  - Symposium on molecular biology and radiation protection.

PMID- 7568764
TI  - Relationship between cataracts and epilation in atomic bomb survivors.
AB  - Among 1713 atomic bomb survivors who underwent ophthalmological examinations from
      1963-1964, the risk of cataract formation per unit dose of radiation was
      significantly greater for those who reported hair loss of 67% or more after
      exposure (the epilation group) than for those who reported less or no hair loss
      (the no-epilation group) (P < 0.01). Such an epilation effect has also been
      associated with leukemia mortality and the frequency of chromosome aberrations.
      Although this might be interpreted as indicating differential sensitivity to
      radiation between the epilation group and the no-epilation group, it could also
      be explained by imprecision in dose estimates. We have calculated that a 48%
      random error in DS86 dose estimates could be in accordance with the dose-response
      relationship for the prevalence of cataracts in the epilation group or the no
      epilation group. Possible mechanisms for variation in radiosensitivity are
      discussed.

PMID- 7568765
TI  - The role of dose rate in the induction of micronuclei in deep-lung fibroblasts in
      vivo after exposure to cobalt-60 gamma rays.
AB  - To evaluate the influence of low-dose-rate exposures on biological damage, it is
      necessary to have cells that can be maintained in the same stage of the cell
      cycle for long periods. Normal rat lung fibroblasts represent a stable cell type
      with a slow turnover rate in vivo. These cells can be stimulated to divide by
      placing them in tissue culture. Therefore, a constant cell population can be
      exposed over a protracted time and stimulated to divide, and the cytogenetic
      damage can be evaluated at the first cell division after exposure. By placing
      rats at different distances from a 60Co source, they were exposed to graded doses
      of gamma rays--0.0, 3.9, 7.4 and 11.3 Gy--protracted over either 4 or 67 h.
      Fibroblasts were isolated from the lung and cultured for 24 h; after cytochalasin
      B was added, the cells were cultured for an additional 69 to 72 h. The percentage
      binucleated cells in fibroblasts of animals exposed for 4 or 67 h was 47.1 +/-
      4.3 and 62.1 +/- 3.9. There was no influence of dose on the percentage
      binucleated cells, but the fraction of cells that divided at 67 h was
      significantly higher (P < 0.05) than observed at 4 h. Cells were scored for
      micronuclei on coded slides. The dose-response data from animals exposed for 4
      and 67 h were fitted to the following linear dose-response relationships, where D
      = dose; micronuclei/binucleated cell = 0.02 +/- 0.03 + 2.38 +/- 0.44 x 10(-2) D,
      and micronuclei/binucleated cell = 0.01 +/- 0.06 + 1.01 +/- 0.10 x 10(-2) D,
      respectively. The r2 values for the two curves were 0.67 and 0.91, indicating the
      goodness of fit for the data for the 4- and 67-h treatments. The slopes were
      different from zero and each other at the P < 0.05 level of significance. The
      effectiveness of the 60Co exposure decreased as the dose rate decreased. At dose
      rates below 0.17 Gy/h, the effectiveness remained constant over the range of
      doses and dose rates used. Comparing the slope of the dose response for the
      lowest exposure rate to that from information published previously, the dose-rate
      effectiveness factor was 6.14 +/- 0.65 for the induction of micronuclei in deep
      lung fibroblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7568768
TI  - Induction and rejoining of DNA double-strand breaks and interphase chromosome
      breaks after exposure to X rays in one normal and two hypersensitive human
      fibroblast cell lines.
AB  - The aim of this work was to measure simultaneously and in a quantitative manner
      double-strand breaks (DSBs), interphase chromosome breaks and cell lethality
      either immediately after irradiation, or at various times thereafter (up to 24
      h), in cells of three nontransformed human fibroblast cell lines of widely
      different intrinsic radiosensitivity. We wished to assess initial damage, repair
      kinetics and residual damage at the DNA and the chromosome level, and to
      correlate these parameters with cell killing. We employed HF19 cells, a normal
      fibroblast cell line, AT2 cells, a radiosensitive cell line from a patient
      suffering from ataxia telangiectasia (AT), and 180BR cells, a radiosensitive cell
      line from a patient with no clinical symptoms of AT. AT2 and 180BR cells, in
      addition to being radiosensitive, also display a reduced ability to repair
      potentially lethal damage compared to HF19 cells. The yield of DSBs, as measured
      by pulsed-field gel electrophoresis, is similar in all three cell lines (slopes
      correspond to 1.6-1.7% Gy-1 of DNA-associated radioactivity released from the gel
      well into the lane). In contrast, residual DSBs measured 24 h after irradiation
      are almost zero for HF19 cells (0.1% confidence interval = 0-1.4%), but are 12.5%
      (+/- 2.3%) and 43.8% (+/- 1.2%) of those measured immediately after irradiation
      in AT2 and 180BR cells, respectively. Residual interphase chromosome breaks are
      11.6% (+/- 1.6%), 29.7% (+/- 5.7%) and 41.4% (+/- 2.2%) of those measured
      immediately after irradiation in HF19, AT2 and 180BR cells, respectively. Neither
      the initial yield of DSBs nor that of excess interphase chromosome breaks can
      explain the differences in radiosensitivity between the three cell lines;
      however, there is a correlation between residual DSBs, rate of DSB rejoining at
      24 h, residual interphase chromosome breaks on the one hand and cell survival on
      the other hand.

PMID- 7568767
TI  - Short exposures to 60 Hz magnetic fields do not alter MYC expression in HL60 or
      Daudi cells.
AB  - Analysis of changes in gene expression induced by 60 Hz magnetic fields has been
      considered to support an association between exposure to magnetic fields and
      cancer risk. Several reports have indicated that these fields rapidly activate
      many genes in mammalian cells. However, previous studies in this area have not
      provided sufficient information to support the conclusions drawn. To clarify this
      controversial research, we have attempted to validate, under rigorously
      controlled conditions, key experiments on induction of gene expression by
      magnetic fields. An extensive series of experiments, incorporating critical
      improvements in experimental design, most notably blind exposures and internal
      standards, was performed with human HL60 and Daudi cells. Exposure conditions
      covered a range of flux densities (5.7 microT to 10 mT) and times (20-60 min). No
      alteration in the human MYC gene, commonly referred to as c-myc, or beta-actin
      steady-state mRNA levels was observed. The lack of an effect was not attributable
      to exposure geometry, timing of RNA preparation, or serum lot and concentration.
      To eliminate any remaining variables, exact replication was performed in one of
      the laboratories previously reporting gene expression effects; again, no evidence
      for altered MYC expression was found. Finally, differential display PCR indicated
      that extremely low-frequency magnetic field-induced changes in gene expression
      were not prevalent.

PMID- 7568769
TI  - Radiation-induced cell lethality of Salmonella typhimurium ATCC 14028:
      cooperative effect of hydroxyl radical and oxygen.
AB  - The lethality of gamma-radiation doses of 0.2 to 1.0 kGy for Salmonella
      typhimurium ATCC 14028 was measured in the presence of air, N2 and N2O and with
      the hydroxyl radical scavengers formate and polyethylene glycol (PEG), M(r)
      8,000. Saturation of cell suspensions with either N2O or N2/N2O (1:1, v/v) gas
      was expected to double the number of hydroxyl radicals (OH.) and to produce an
      equivalent increase in lethality, but this did not occur. Adding 10% (v/v) O2 to
      either N2 or N2O gas produced approximately the same gamma-irradiation lethality
      for S. typhimurium as did air. Addition of hydroxyl radical scavengers, 40 mM
      formate and 1.5% (w/v) PEG, significantly reduced the lethality of gamma
      radiation for S. typhimurium in the presence of air but not in the presence of N2
      or N2O gases. Membrane-permeable formate provided slightly better protection than
      nonpermeable PEG. Cells of S. typhimurium grown under anaerobic conditions were
      more sensitive to radiation, and were less protected by hydroxyl radical
      scavengers, especially formate, than when cells grown under aerobic conditions
      were irradiated in the presence of oxygen. Hydroxyl radical scavengers provided
      no further protection during irradiation in the absence of oxygen. These results
      indicated that the increased radiation sensitivity of cells grown under anaerobic
      conditions may be related to superoxide radicals which could increase
      intercellular damage during irradiation in the presence of oxygen. However,
      endogenous superoxide dismutase and catalase activities did not protect cells
      from the radiation-induced lethality of S. typhimurium. Cytoplasmic extracts
      protected bacterial DNA in vitro in either the presence or absence of oxygen, and
      no radiation-induced lipid peroxidation of the cellular components was identified
      by measuring the levels of 2-thiobarbituric acid. These results suggest that most
      radiation-induced cell lethality was related to the cooperative effects of
      extracellular OH. and O2 on the cell surface as the radiation dose increased.

PMID- 7568771
TI  - A novel approach to the microdosimetry of neutron capture therapy. Part I. High
      resolution quantitative autoradiography applied to microdosimetry in neutron
      capture therapy.
AB  - A novel approach to the microdosimetry of neutron capture therapy has been
      developed using high-resolution quantitative autoradiography (HRQAR) and two
      dimensional Monte Carlo simulation. This approach has been applied using actual
      cell morphology (nuclear and cytoplasmic cell structures) and the measured
      microdistribution of boron-10 in a transplanted murine brain tumor (GL261)
      containing p-boronophenylalanine (BPA) as the boron compound. The 2D Monte Carlo
      transport code for the alpha and 7Li charged particles from the 10B(n,alpha)7Li
      reactions has been developed as a surrogate to a full 3D approach to calculate a
      variety of different microdosimetric parameters. The HRQAR method and the
      surrogate 2D Monte Carlo approach are described in detail and examples of their
      use are presented.

PMID- 7568770
TI  - The effect of dimethyl sulfoxide on the induction of DNA double-strand breaks in
      V79-4 mammalian cells by alpha particles.
AB  - The present study was undertaken to assess the protective effect of dimethyl
      sulfoxide (DMSO) against the induction and rejoining of DNA double-strand breaks
      (DSBs) and inactivation of V79-4 Chinese hamster cells by both high- and low
      linear energy transfer (LET) radiations. The cells were exposed under aerobic
      conditions as monolayers to either low-LET photons (60Co gamma rays) or high-LET
      alpha particles (238Pu) at 277 K. The initial yield of DSBs, determined by
      elution under nondenaturing conditions, is linearly dependent on dose. When the
      irradiation was carried out in the presence of DMSO (0-0.6 mol dm-3), the initial
      yields of DSBs induced by both gamma and alpha-particle irradiation decrease.
      With gamma irradiation at [DMSO] > 0.6 mol dm-3, a further decrease in the yield
      of DSBs occurs. DMSO (0.5 mol dm-3) reduces the initial yield of DSBs by 50 +/-
      5% and 32 +/- 4% for photons and alpha particles, respectively. DMSO protects
      more effectively against cellular inactivation and DSB induction at low LET
      compared with alpha-particle irradiation with protection factors of 1.7 and 1.4,
      respectively, for survival and 2.0 and 1.5, respectively, for DSBs. After
      incubation of the irradiated cells for 3 h at 310 K after high-LET irradiation,
      the residual yield of DSBs is reduced by < 13% when the irradiations were carried
      out in the presence of 0.5 mol dm-3 DMSO. With gamma irradiation in the presence
      of 0.5 mol dm-3 DMSO, 90% of the DSBs are rejoined by 3 h incubation at 310 K.
      Therefore, the nonscavengeable DSBs induced by alpha particles are not
      significantly rejoined within 3 h, in contrast to rejoining of the majority of
      the nonscavengeable DSBs induced by gamma irradiation. From comparison of the
      data on DSBs and survival for alpha-particle irradiation, it is inferred that the
      severity of damage is reduced by DMSO through minimizing the formation of OH
      induced sugar/base modifications in the vicinity of nonscavengeable DSBs.

PMID- 7568774
TI  - Hepatic effects of inhaled plutonium dioxide in beagles.
AB  - The effects of inhaled 238PuO2 deposited in the liver of dogs were studied in
      beagles exposed to initial lung depositions ranging from 5.7 to 2979.7 Bq/g lung.
      Approximately 20% of the initial lung deposition was translocated to the liver by
      1500 days after exposure. Life-span observations revealed that the liver
      contained 40% of the final body burden of plutonium, second only to the skeleton.
      Elevated serum liver enzyme activities were observed in dogs with final liver
      depositions of > or = 0.4 Bq/g, cumulative dose to the liver of > or = 0.18 Gy
      and annual dose rate > or = 0.02 Gy/year. Enzyme elevations were seen at one dose
      level lower than that in which bone or lung tumors were observed. Linear
      regression analysis revealed strong to moderate correlation between cumulative
      dose and dose rate and time to observed increases in liver enzyme activities.
      Liver tumors were late-occurring neoplasms observed at lower exposure levels
      where life span was not shortened by lung and bone tumors.

PMID- 7568772
TI  - The effects of boron on the electron paramagnetic resonance spectra of alanine
      irradiated with thermal neutrons.
AB  - The effects of boric acid admixture on the intensity and line structure of EPR
      spectra of free radicals produced in alanine by thermal neutrons are presented.
      The EPR signal enhancement, up to a factor of 40 depending on the boron
      concentration, is related to additional energy deposition in alanine crystals by
      the disintegration products resulting from the capture of a thermal neutron by
      boron, 10B(n,alpha)7Li. The changes in the shape of the EPR spectra observed by
      changing the microwave power are due to the differences in the microwave power
      saturation of the free radicals produced by a low-LET radiation and those
      produced by the high-LET components of the radiation after the neutron capture
      reaction.

PMID- 7568775
TI  - Relative biological effectiveness of tritium for induction of myeloid leukemia in
      CBA/H mice.
AB  - To help resolve uncertainties as to the most appropriate weighting factor for
      tritium beta rays, a large experiment was carried out to measure the relative
      biological effectiveness (RBE) of tritiated water compared to X rays for the
      induction of myeloid leukemia in male mice of the CBA/H strain. The study was
      designed to estimate the lifetime incidence of myeloid leukemia in seven groups
      of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy
      both for tritiated water and for X rays. The lifetime incidence of leukemia in
      these mice increased from 0.13% in the control group to 6-8% in groups exposed to
      higher radiation doses. The results were fitted to various equations relating
      leukemia incidence to radiation dose, using both the raw data and data corrected
      for cumulative mouse-days at risk. The calculated RBE values for tritium beta
      rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate
      of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus
      appear to be more appropriate than a wR of 2 for tritium beta rays.

PMID- 7568773
TI  - Effect of in vivo heart irradiation on the development of antioxidant defenses
      and cardiac functions in the rat.
AB  - During radiotherapy of thoracic tumors, the heart is often included in the
      primary treatment volume, and chronic impairment of myocardial function occurs.
      The cellular biomolecules are altered directly by radiation or damaged indirectly
      by free radical production. The purpose of this investigation was to evaluate the
      biochemical and functional responses of the rat heart to a single high dose of
      radiation. The effect of 20 Gy local X irradiation was determined in the heart of
      Wistar rats under general anesthesia. Mechanical performances were measured in
      vitro using an isolated perfused working heart model, and cardiac antioxidant
      defenses were also evaluated. Hearts were studied at 1 and 4 months after
      irradiation. This single dose of radiation induced a marked drop in the
      mechanical activity of the rat heart: aortic output was significantly reduced
      (18% less than control values) at 1 month postirradiation and remained depressed
      for the rest of the experimental period (21% less than control 4 months after
      treatment). This suggests the development of myocardial failure after
      irradiation. The decline of functional parameters was associated with changes in
      antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was
      associated with an increase in the levels of Mn-SOD and glutathione peroxidase
      (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac
      vitamin C and catalase levels remained constant. Since these antioxidant defenses
      were activated relatively long after irradiation, it is suggested that this was
      probably due to the production of free radical species associated with the
      development of inflammation.

PMID- 7568776
TI  - No effect of 60 Hz electromagnetic fields on MYC or beta-actin expression in
      human leukemic cells.
AB  - Epidemiological studies have shown weak correlations between exposure to
      extremely low-frequency electromagnetic fields (ELF EMFs) and the incidence of
      several cancers, particularly childhood leukemias, although negative studies have
      also been reported. These observations have prompted a broad range of in vitro
      cellular studies in which effects of ELF EMFs have been observed. However, no
      reported response has been replicated widely in independent laboratories. One
      potentially important response is the rapid activation of proto-oncogenes and
      other genes in human leukemic (HL60) cells and a wide variety of other eukaryotic
      cells, because of the role of these genes in cell proliferation. We describe
      quantitative Northern analysis of MYC and beta-actin mRNAs from HL60 cells
      exposed to fields under conditions very similar to those reported previously to
      activate these genes, namely 60 Hz sinusoidal magnetic fields of 0.57, 5.7 or 57
      microT for 20 min. In addition we have used a new design of field-exposure system
      and introduced a number of other modifications to the protocol to optimize any
      response. We have also developed a novel method providing enhanced accuracy for
      the quantitative measurement of mRNA. No significant effect of ELF EMFs on gene
      expression was observed using any of these systems and analytical methods.

PMID- 7568777
TI  - Effect of cell cycle stage, dose rate and repair of sublethal damage on radiation
      induced apoptosis in F9 teratocarcinoma cells.
AB  - There are at least two different modes of cell death after treatment with
      ionizing radiation. The first is a failure to undergo sustained cell division
      despite metabolic survival, and we refer to this end point as "classical
      reproductive cell death." The second is a process that results in loss of cell
      integrity. This second category includes cellular necrosis as well as apoptosis.
      Earlier studies in our laboratory showed that the predominant mechanism of cell
      death for irradiated F9 cells is apoptosis, and there is no indication that these
      cells die by necrosis. We have therefore used cells of this cell line to reassess
      basic radiobiological principles with respect to apoptosis. Classical
      reproductive cell death was determined by staining colonies derived from
      irradiated cells and scoring colonies of less than 50 cells as reproductively
      dead and colonies of more than 50 cells as survivors. Cells that failed to
      produce either type of colony (detached from the plate or disintegrated) were
      scored as having undergone apoptosis. Using these criteria we found that the
      fraction of the radiation-killed F9 cells that died by apoptosis did not vary
      when cells were irradiated at different stages of the cell cycle despite large
      variations in overall survival. This suggests that the factors that influence
      radiation sensitivity throughout the cell cycle have an equal impact on apoptosis
      and classical reproductive cell death. There was no difference in cell survival
      between split doses and single doses of X rays, suggesting that sublethal damage
      repair is not a factor in radiation-induced apoptosis of F9 cells. Apoptosis was
      not affected by changes in dose rate in the range of 0.038-4.96 Gy/min.

PMID- 7568778
TI  - Chromosome aberrations induced in human lymphocytes after partial-body
      irradiation.
AB  - Chromosomal aberrations in peripheral blood lymphocytes obtained from two
      patients before and after they received one fraction of partial-body irradiation
      for palliative treatment were analyzed. Blood samples were taken 30 min and 24 h
      after radiation treatment. The yield of dicentrics obtained from case A 30 min
      after a partial-body (about 21%) treatment with 8 Gy was 0.066/cell, while the
      yield obtained 24 h after radiation treatment was 0.071/cell. The fraction of
      irradiated lymphocytes that reached metaphase at 52 h was 0.08 as evaluated by
      mixing cultures of in vitro irradiated and unirradiated blood. The yield of
      dicentrics for blood from case B 30 min after 6 Gy partial-body (about 24%)
      irradiation was 0.655/cell, while the yield 24 h after irradiation was
      0.605/cell. The fraction of irradiated cells was 0.29. Estimation of doses and
      irradiated fractions for the two cases using the method proposed by Dolphin and
      the Qdr method is discussed. Although there was no significant difference between
      the mean yields of dicentrics per cell obtained 30 min and 24 h after radiation
      treatment, the data obtained at 24 h seemed more useful for the purpose of dose
      estimation. When a higher dose (8 Gy) was delivered to a smaller percentage of
      the body, underestimation of the dose was encountered.

PMID- 7568779
TI  - Outcomes study of attrition in a two-year R.T. program.
AB  - This article examines whether there is a statistically significant relationship
      between admission criteria and other related student characteristics to attrition
      rates in radiologic science programs at two-year community colleges. The study
      reported in this article investigated 179 students admitted during a 10-year
      period to a radiography program at a Midwestern community college. Investigators
      found that admission criteria were not correlates of student success or failure,
      indicating a need for further research into cognitive and non-cognitive factors.

PMID- 7568780
TI  - Managers' expectations of radiographers: a survey.
AB  - Radiology department managers in eight Southeastern states were surveyed
      regarding their expectations of radiographers. Results indicated that managers
      expected radiographers to be multicompetent, possess communication skills,
      participate in quality assessment and continuous quality improvement programs,
      practice cost containment, be aware of legal and ethical responsibilities,
      display an interest in supervisory skills and practice basic radiography. The
      survey also showed that managers believe these expectations often are not
      fulfilled.

PMID- 7568781
TI  - Radiology's role in diagnosis of AIDS-related pathologies.
AB  - Secondary infections and malignancies are responsible for the majority of deaths
      among AIDS patients. Medical imaging plays a significant role in the diagnosis
      and treatment of these pathologies. Many opportunistic infections and
      malignancies can be imaged with conventional radiography and fluoroscopy,
      sonography, computed tomography, magnetic resonance imaging and nuclear medicine
      studies. This article describes AIDS-related pathologies and discusses diagnostic
      imaging's role in their early detection and treatment.

PMID- 7568782
TI  - Special techniques and projections.

PMID- 7568783
TI  - The challenge of outcomes assessment.

PMID- 7568784
TI  - 'You were wrong!'.

PMID- 7568789
TI  - The case of the corrugated coif.

PMID- 7568786
TI  - Radiography's role in detecting child abuse.

PMID- 7568785
TI  - Understanding temporomandibular disorder.

PMID- 7568787
TI  - The registry's PR campaign.

PMID- 7568788
TI  - Mandatory CE--time to move on?

PMID- 7568790
TI  - The mammography patient history sheet.

PMID- 7568791
TI  - To grow, we must change.

PMID- 7568792
TI  - [New super-paramagnetic iron particles for MRI. Phase II study of malignant liver
      tumors].
AB  - The clinical tolerability and diagnostic value of Resovist as a new
      superparamagnetic iron oxide contrast medium was studied in 30 patients with
      malignant focal liver lesions (28 metastases, 2 HCC) within a phase II
      multicenter study. Magnetic resonance imaging (MRI) was performed at 1.0 Tesla
      with T1-weighted FLASH- and T2-weighted spin echo sequences before and following
      intravenous injection of Resovist at three different dose groups (4, 8 and 16
      mumol Fe/kg). Liver signal intensity was significantly reduced on post-contrast
      images, while malignant focal liver lesions showed no signal changes. Resovist
      improved tumor liver contrast and lesion-conspicuity, especially for lesions
      smaller than 1 cm. The dose of 8 mumol Fe/kg was sufficient to achieve diagnostic
      tumor-liver contrast. Compared to images directly after injection, the number of
      detected lesions did not improve until 70 min later. There were no significant
      changes in vital signs (heart rate, blood pressure) or laboratory values until 72
      h post-injection.

PMID- 7568793
TI  - [Magnetic resonance tomography of the scrotum. Experiences with 129 patients].
AB  - In our study 129 patients underwent MR imaging for evaluation of the scrotum with
      spin-echo pulse sequence (proton density and T2-weighted images). The final
      diagnosis was confirmed by surgery in 54 patients. Our findings show that MRI is
      a powerful supplementary technique for scrotal imaging when ultrasound findings
      are unclear or are inconsistent with the clinical history. MRI can reduce the
      number of unnecessary exploratory operations on the testis, though surgery is
      unavoidable if the findings are equivocal. Differentiation and specification of
      tumours cannot be achieved by MRI, nor does it allow accurate evaluation of
      subacute torsion of the testis. In these cases dynamic MRT following intravenous
      administration of Gd-DTPA may improve the diagnostic accuracy.

PMID- 7568794
TI  - [The MRI in pre- and postnatal diagnosis of congenital sacrococcygeal teratoma].
AB  - INTRODUCTION: The main tasks of imaging methods on the evaluation of relatively
      rare and potentially malignant connatal sacrococcygeal teratomas (SCT) are to
      depict the extent, structure and relationship to surrounding systems. METHODS:
      Two cases with SCT were studied with pre- and postnatal MRI and findings were
      compared with the ultrasound and clinical data. RESULTS: Before delivery, MRI
      permits depiction of the size and structure of teratomas and the integrity of the
      serum. After delivery, evaluation of the rectum, urinary tract and levator
      muscles is important to facilitate surgical reconstruction.

PMID- 7568797
TI  - [Diagnosis of an infected thrombus of the inferior vena cava with ultrasound and
      computerized tomography].
AB  - The incidence of central venous catheter-associated thrombosis is up to 66%;
      nevertheless, in most cases it is of little clinical importance. A rare, but
      serious complication is infection of a catheter-associated thrombosis, which
      occurs in 7-16%. We report the case of a 16-year-old male patient, who suffered
      from meningitis and Waterhouse-Friderichsen syndrome. After initial improvement
      in the intensive care unit, he developed septic temperatures, caused by an
      infected thrombus of a central venous catheter in the inferior vena cava. Color
      coded ultrasound showed hyperechogenic signals and missing flow detection at the
      catheter tip. Computed tomography showed air bubbles in the thrombosed catheter
      tip and confirmed the diagnosis. Vascular surgery was done and an infected, 17-cm
      long infected thrombus was removed. The recent literature on this topic is
      reviewed.

PMID- 7568798
TI  - [Indirect azygos vein continuation syndrome with segmental agenesis and saccular
      aneurysm of the inferior vena cava].
AB  - Indirect vena azygos continuation syndrome and aneurysm are rare variations of
      the inferior vena cava (IVC). In this article we describe the ultrasound,
      angiographic and CT appearance of a 14-year-old girl with this congenital
      anormaly of the IVC.

PMID- 7568796
TI  - [Computerized tomography diagnosis of a secondary extramedullary situated, non
      secreting plasmacytoma of the right plica ventricularis].
AB  - We report the case of a 62-year-old male patient with an extramedullary non
      secreting plasmacytoma of the right plica ventricularis. Although his skeletal
      lesions remained stable, the patient developed hoarseness. This was interpreted
      as mycotic laryngitis and computed tomography showed a tumor of the right plica
      ventricularis. Differential diagnosis included neoplasms of the larynx, thyroid
      gland or a lymphoma. After biopsy, however, histology revealed the rare diagnosis
      of a secondary extramedullary non-secreting plasmacytoma.

PMID- 7568795
TI  - [Diagnosis of cerebral metastasis with standard dose gadobutrol vs. a high dose
      protocol. Intraindividual evaluation of a phase II high dose study].
AB  - PURPOSE: To assess the effectiveness and safety of normal and high doses of
      Gadobutrol versus a standard dose of Gadolinium DTPA in the MR evaluation of
      patients with brain metastases. MATERIAL AND METHODS: In a clinical phase-II
      study 20 patients who had been diagnosed as having brain metastases with CT or
      MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality
      contrast agent. Each patient received an initial injection of 0.1 mmol/kg body
      weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spin-echo
      images were obtained before and after the two applications of Gadobutrol. Dynamic
      scanning (Turbo-FLASH) was performed for 3 min after each injection of the
      contrast agent. Both quantitative and qualitative data were intraindividually
      evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other
      cases there were different primary tumors. RESULTS: Forty-eight hours after the
      use of Gadobutrol there were no adverse signs in the clinical examination, vital
      signs or blood and urine chemistry. Statistical analysis (Friedman test and
      Wilcoxon test) of the C/N ratios between tumor and white matter, percentage
      enhancement, and visual assessment rating revealed statistically significant
      superiority of high-dose Gadobutrol injection in comparison to the standard dose.
      The percentage enhancement increased on average from 104% after 0.1 mmol/kg to
      162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the
      lesions increased significantly. The use of high-dose Gadobutrol improved the
      detection of 36 additional lesions in 6 patients. CONCLUSION: The first in vivo
      results prove the excellent contrast capacity of the nonionic contrast agent
      Gadobutrol for the diagnosis of intracerebral metastases.

PMID- 7568799
TI  - [POEMS syndrome].
AB  - The POEMS-syndrome is a very rare disorder, of which not much more than 100 cases
      are known worldwide, mostly in Japan. The following case report depicts the
      typical radiological changes to the skeletal system and inner organs.

PMID- 7568800
TI  - [Coincidence of unifocal thyroid autonomy and follicular carcinoma. Case report].
AB  - The case is reported of a 53-year-old man with differentiated thyroid carcinoma
      within a hot nodule and typical scintigraphic findings of a unifocal adenoma.
      Preoperative cytology revealed no malignancy. The preliminary histological
      diagnosis after hemithyroidectomy on the right side was follicular adenoma. The
      final histological evaluation, however, revealed follicular carcinoma of the
      thyroid gland. As a result, a thyroidectomy was performed with postoperative
      radioiodine treatment. The combination of thyroid carcinoma and hot nodules is
      extremely rare. In all cases of rapid growing nodules or other abnormalities of
      the thyroid cytological and/or histological verification is mandatory.

PMID- 7568801
TI  - [Indications for percutaneous radiotherapy in carcinoma of the thyroid gland.
      Freiburg consensus].
AB  - At the University of Freiburg, a consensus was arrived at concerning the place of
      external radiotherapy in the management of thyroid cancer. External irradiation
      is always indicated in papillary and folliculary carcinoma in the pT4 stage of
      pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph
      node metastases and distant metastases, an individual treatment concept is
      recommended, which should be set up in an interdisciplinary conference regarding
      all risk factors, especially the age and sex of the patient, the histology and
      grading of the tumor and the completeness of tumor resection. Finally,
      radiotherapy is usually not indicated in medullary thyroid carcinoma, whereas it
      is always indicated in anaplastic carcinoma.

PMID- 7568804
TI  - [32nd Annual meeting of the Society for Pediatric Radiology. Wurzburg, 22-23
      September 1995. Abstracts].

PMID- 7568802
TI  - [Refractory ulcer of the left breast].

PMID- 7568803
TI  - [Abdominal space-occupying lesion. Bilateral pheochromocytoma in MEN IIa and well
      differentiated retroperitoneal liposarcoma].

PMID- 7568805
TI  - Airways and lung: correlation of CT with fiberoptic bronchoscopy.
AB  - Recent advances in computed tomography (CT) and fiberoptic bronchoscopy (FOB)
      have led to confusion concerning the optimal use of these modalities, especially
      with regard to each other. The present review summarizes the current
      understanding of the role of CT in relation to FOB. Emphasis is placed on
      optimization of CT technique and basic principles of interpretation of the
      images. In addition, an in-depth evaluation is presented of the advantages and
      limitations of CT and FOB in the analysis of both focal and diffuse diseases of
      the airways and lung parenchyma.

PMID- 7568807
TI  - Bile duct obstruction and choledocholithiasis: diagnosis with MR cholangiography.
AB  - PURPOSE: To evaluate the accuracy of magnetic resonance (MR)
      cholangiopancreatography in the diagnosis of bile duct obstruction. MATERIALS AND
      METHODS: One hundred twenty-six patients with clinically suspected bile duct
      obstruction underwent MR cholangiopancreatography with heavily T2-weighted fast
      spin-echo sequences. Reviewers were blinded to clinical and imaging findings.
      RESULTS: Seventy-nine patients had biliary obstruction that was diagnosed with MR
      cholangiopancreatography in 72 patients for a sensitivity of 91%, specificity of
      100%, and overall accuracy of 94%. Thirty-two patients had choledocholithiasis
      that was diagnosed with MR cholangiopancreatography in 26 patients for an
      accuracy of 94%, sensitivity of 81%, specificity of 98%, positive predictive
      value of 93%, and negative predictive value of 94%. Fourteen patients had
      malignant obstruction that was diagnosed with MR cholangiopancreatography in 12
      patients for a sensitivity and a positive predictive value of 86%, specificity
      and negative predictive value of 98%, and accuracy of 97%. CONCLUSION: MR
      cholangiopancreatography is a noninvasive technique with excellent accuracy in
      the diagnosis of bile duct obstruction and its causes.

PMID- 7568806
TI  - Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of
      percutaneous ethanol injection.
AB  - PURPOSE: To define indications for percutaneous ethanol injection (PEI) in
      patients with hepatocellular carcinoma (HCC) and cirrhosis. MATERIALS AND
      METHODS: Survival rates were determined in 746 patients who had undergone PEI
      (567 men, 179 women; mean age, 64.3 years; mean follow-up, 36 months). RESULTS:
      In patients with Child A (n = 293), B (n = 149), or C (n = 20) cirrhosis and
      single HCCs 5 cm or smaller, the 3-5 year survival rate was 47%-79%, 29%-63%, and
      0%-12%, respectively. In patients with Child A cirrhosis, it was 36%-68% for
      multiple HCCs (n = 121), 30%-53% for single HCCs larger than 5 cm (n = 28), and
      0%-16% for advanced HCC (n = 16). Treatment was associated with a 1.7% rate of
      severe complications and a 0.1% mortality rate. CONCLUSION: PEI proved safe,
      effective, and repeatable and had a low cost. Survival after PEI was comparable
      to that after surgery, probably because of a balancing between greater radicality
      of surgery and absence of early mortality and liver damage of PEI.

PMID- 7568809
TI  - Blunt traumatic aortic rupture: detection with helical CT of the chest.
AB  - PURPOSE: To determine the effectiveness of helical computed tomography (CT) as a
      screening device to detect traumatic aortic rupture. MATERIALS AND METHODS:
      Helical CT was used to examine 1,518 patients with nontrivial blunt trauma. Of
      these patients, 127 (8.37%) with abnormal CT scans of the mediastinum or aorta
      underwent thoracic aortography--89 patients solely for evaluation of mediastinal
      hematoma depicted at CT. Imaging abnormalities were correlated with surgical or
      clinical outcome. RESULTS: Twenty-one aortic injuries were identified that ranged
      from subtle intimal flaps to complete aortic disruption. Helical CT was more
      sensitive than aortography (100% versus 94.4%, respectively) but less specific
      (81.7% versus 96.3%, respectively) in detection of aortic injuries in patients
      who underwent both examinations. The association between CT findings and outcome
      was phi = 0.62 (chi2 = 49.1, 1 df, P < .01) and between aortography and outcome
      was phi = 0.85 (chi2 = 92.2, 1 df, P < .001). The P value of the difference
      between the phi coefficients was .10. CONCLUSION: Helical CT of the chest is
      effective for screening critically injured patients with possible blunt thoracic
      aortic injuries.

PMID- 7568810
TI  - Can helical CT replace aortography in thoracic trauma.

PMID- 7568808
TI  - Intramural mechanics in hypertrophic cardiomyopathy: functional mapping with
      strain-rate MR imaging.
AB  - PURPOSE: To characterize systolic and diastolic intramural mechanics in
      hypertrophic cardiomyopathy (HCM) with a new metric of contractile activity.
      MATERIALS AND METHODS: Eleven healthy subjects and eight patients with HCM
      underwent velocity-encoded echo-planar magnetic resonance (MR) imaging (6-8-frame
      gated breath-hold movies, 3 x 3-mm resolution). A scalar strain rate (SR)
      parameter was compared with wall thickness and symptoms. RESULTS: The normal
      pattern of SR included regional uniformity, a monotonically increasing
      subepicardial to subendocardial gradient, and minimum transmural shear rate. In
      HCM, heterogeneity of SRs increased in diastole. Regional diastolic SR correlated
      with regional wall thickness (r = .785, P = .0001). Interobserver global SR
      assignment agreed in seven of eight patients. All four patients with New York
      Heart Association class 1 disease had a low global SR deficit score, whereas
      three of four patients with class 2 or 3 disease had a high SR deficit score
      (Spearman r = .775, P = .187). CONCLUSION: SR characterization may provide an
      objective measure of disease course in HCM.

PMID- 7568811
TI  - Mural thrombi in abdominal aortic aneurysms: MR imaging characterization--useful
      before endovascular treatment?
AB  - PURPOSE: To evaluate magnetic resonance (MR) imaging accuracy in the
      characterization of mural thrombi in abdominal aortic aneurysms (AAAs). MATERIALS
      AND METHODS: Forty-five patients (37 men, eight women; mean age, 68 years) with
      an AAA with mural thrombus thicker than 1 cm at sonography underwent T1- and T2
      weighted spin-echo MR imaging. The thrombi were prospectively classified as one
      of three signal intensity (SI) categories: category 1 corresponds to low SI on
      both T1- and T2-weighted images; category 2, high SI on T1-and T2-weighted
      images; and category 3, inhomogeneous SI with hyperintense areas on both T1- and
      T2-weighted images. During surgery, thrombi were classified as organized,
      unorganized, and partially organized. MR imaging and surgical findings were
      compared. RESULTS: SI category 1 corresponded to organized thrombi in 24 of 24
      patients. Category 2 corresponded to unorganized thrombi in 11 of 11 patients. In
      category 3, focal hyperintense areas corresponded (both for presence and
      location) to unorganized portions of partially organized thrombi in 10 of 10
      patients. CONCLUSION: MR imaging is accurate in AAA thrombus characterization.

PMID- 7568812
TI  - Thrombolysis of lower extremity embolic occlusions: a study of the results of the
      STAR Registry.
AB  - PURPOSE: To evaluate thrombolysis as primary therapy for lower extremity embolic
      occlusions. MATERIALS AND METHODS: Forty-five of 306 consecutive cases of lower
      extremity arterial occlusions treated with urokinase and registered in the
      Society of Cardiovascular and Interventional Radiology Transluminal Angioplasty
      and Revascularization Registry were believed on the basis of clinical and
      angiographic findings to be due to emboli. RESULTS: Comorbidity included atrial
      fibrillation in 50%, previous myocardial infarction in 40%, and a cerebrovascular
      event in 35%. Thirty-two (71%) limbs were viable, 12 (27%) were threatened, and
      one had irreversible ischemia. Mean symptom duration was 8.6 days. Average
      occlusion length was 17 cm. The distribution of emboli was 4% aortoiliac, 65%
      femoropopliteal, 24% tibial, and 7% graft. Major complications occurred in eight
      of 45 patients (18%). The technical success rate was 69%, with a 1- and 2-year
      primary patency of 79% for initially successful intraarterial thrombolyses.
      CONCLUSION: Thrombolysis of embolic occlusions is successful in most cases. Limb
      salvage and survival rates are similar to historical reports for surgical
      embolectomy.

PMID- 7568813
TI  - Portal vein patency in candidates for liver transplantation: MR angiographic
      analysis.
AB  - PURPOSE: To assess the accuracy of magnetic resonance (MR) angiography for
      evaluating portal vein patency in candidates for liver transplantation. MATERIALS
      AND METHODS: MR angiography was performed in the main portal vein and proximal
      confluence of the portal vein in 102 candidates for liver transplantation (64
      male patients and 38 female patients aged 8 months to 74 years; mean age, 47
      years). The MR angiographic results were compared with the surgical and
      histologic findings in the explanted liver and excised main portal vein. RESULTS:
      MR angiography depicted 10 portal vein clots, all of which were confirmed at
      transplantation. Ninety-two portal veins were patent at MR angiography, a finding
      that was confirmed at transplantation. One tiny chronic clot in a small,
      intrahepatic branch of the portal vein was not seen at MR angiography or
      transplantation. It was identified at histologic analysis of the explanted liver.
      CONCLUSION: MR angiography is accurate in the evaluation of portal vein patency.

PMID- 7568814
TI  - Percutaneous balloon embolectomy with a self-expanding tulip sheath: in vivo
      experiments.
AB  - PURPOSE: To test a self-expanding tulip-shaped sheath designed for percutaneous
      embolectomy in an in vivo animal experiment. MATERIALS AND METHODS: In nine
      sheep, a total of 23 percutaneous balloon embolectomies were performed with use
      of a self-expanding tulip sheath device with an outer diameter of 9- or 10-F when
      collapsed. A 10-F instrument was used in 11 cases, and a 9-F instrument was used
      in 12. Radiopaque emboli were pushed into the aorta via the left carotid or
      contralateral femoral artery with a 16-F introducer sheath. RESULTS: The embolus
      was captured in the tulip cage in all 23 cases. Retrieval of the embolus into the
      sheath was complete in 21 of 23 cases. In two cases, minor parts of the embolus
      dislodged from the sheath. Major embolism did not occur. In nine cases, the outer
      sheath had to be cleared of remaining clot particles with aspiration. CONCLUSION:
      The noncovered self-expanding tulip sheath is an effective and safe instrument
      for percutaneous embolectomy under in vivo conditions.

PMID- 7568815
TI  - Acute massive pulmonary embolism: use of a rotatable pigtail catheter for
      diagnosis and fragmentation therapy.
AB  - PURPOSE: A modified pigtail catheter for angiographic documentation and
      mechanical fragmentation of pulmonary embolism was evaluated for its efficacy and
      safety. MATERIALS AND METHODS: Rotation of the 5-F pigtail catheter was performed
      with an electric drive or a handle. The wire left an oval side hole at the outer
      curvature and served as an axis of rotation. Fragmentation properties were
      assessed in vitro. Pulmonary positioning, steerability, rotation behavior, and
      safety were tested in six pigs. Pulmonary embolic occlusions were recanalized in
      eight dogs. RESULTS: The catheter system was promptly positioned and easily
      steered in the pulmonary arteries. On average, 53% of the occluded pulmonary
      arteries were recanalized. Recanalization reduced the emboli-induced elevation of
      the pulmonary artery mean pressure by 73%. Slight perivascular hemorrhage
      occurred in three dogs. CONCLUSION: Rapid partial recanalization was achieved
      with relative ease of instrumentation. The technique is an extension of the
      commonly performed pigtail catheterization of the pulmonary arteries, which may
      increase its clinical acceptance.

PMID- 7568816
TI  - Interventional MR imaging.

PMID- 7568817
TI  - Color Doppler sonographic appearance of patent needle tracts after femoral
      arterial catheterization.
AB  - PURPOSE: To determine the color Doppler sonographic characteristics and clinical
      relevance of persistent needle tracts after femoral arterial puncture. MATERIALS
      AND METHODS: After diagnostic (n = 18,825) or interventional (n = 8,489) cardiac
      catheterization, 1,327 color Doppler sonograms of the groin were obtained over a
      54-month period. Gray-scale images, color flow images, pulsed Doppler spectra,
      and clinical records were evaluated. RESULTS: Twenty-one cases of linear tracts
      of pulsatile color flow were identified with accompanying Doppler waveform
      analysis. The mean length and width of the tracts were 21.6 mm (range, 6-33 mm)
      and 2.7 mm (range, 1-5 mm), respectively. Doppler analysis revealed monophasic
      flow only in systole in seven cases, triphasic flow in seven cases, and
      monophasic flow in systole with continued forward flow during diastole in seven
      cases. No tract required surgical repair. CONCLUSION: Color Doppler sonography of
      the groin after femoral arterial catheterization may demonstrate a linear tract
      of color flow that corresponds to the expected path of the needle. These tracts
      do not seem to be clinically important and do not require further color Doppler
      imaging when they represent isolated findings.

PMID- 7568818
TI  - Palmaz stent placement in iliac and femoropopliteal arteries: primary and
      secondary patency in 310 patients with 2-4-year follow-up.
AB  - PURPOSE: To define the long-term outcome of stent placement in iliac and
      femoropopliteal arteries. MATERIALS AND METHODS: Three hundred ten patients
      received 418 balloon-expandable Palmaz stents. Two hundred thirty stents were
      implanted in iliac arteries of 184 patients, and 188 stents were implanted in
      femoropopliteal arteries in 126 patients. Restenosis rates were based on results
      of angiography performed 4-6 months after stent placement. Long-term patency
      rates were determined with duplex ultrasound. RESULTS: Immediate procedural
      success was achieved in 309 patients. Acute thrombosis ( < 24 hours) occurred in
      five patients, and immediate clinical success in 288. The 30-day mortality and
      morbidity rates were 0% and 8%, respectively. Angiography performed at 6 months
      in 299 patients revealed restenosis rates of 0.5% in iliac lesions, 11% in
      superficial femoral artery (SFA) lesions, and 20% in popliteal lesions. Survival
      analysis revealed 4-year primary patency rates of 86% +/- 4.1 for iliac artery
      lesions, 65% +/- 7.5 for SFA lesions, and 50% +/- 17.7 for popliteal artery
      lesions. Most restenotic lesions were successfully treated with repeat
      angioplasty. CONCLUSION: Implantation of Palmaz stents in iliac arteries allows
      long-term primary patency to be maintained in most patients.

PMID- 7568819
TI  - Interactive MR-guided biopsy in an open-configuration MR imaging system.
AB  - PURPOSE: To describe new techniques for percutaneous biopsy with use of an open
      configuration magnetic resonance (MR) imaging system with integrated frameless
      stereotaxic guidance tools. MATERIALS AND METHODS: In 28 patients, biopsy was
      performed in which the image plane was interactively controlled by the position
      of a hand-held probe attached to the biopsy needle. An icon integrated into the
      image was used to guide needle advancement in three planes orthogonal to the
      needle. In vitro measurements of spatial accuracy were also performed. RESULTS:
      Diagnostic tissue was retrieved in 25 of 28 patients. The system was most
      accurate near the isocenter with a maximum measured error of 3.1 mm within a
      sphere of radius 2.5 cm about the isocenter. CONCLUSION: MR-guided biopsy with a
      frameless stereotaxic technique is safe and accurate. Image feedback is near real
      time, and the procedure is interactive. These techniques may be used to perform
      MR-guided biopsies and to place probes for MR-guided therapies.

PMID- 7568820
TI  - Fractional moving blood volume: estimation with power Doppler US.
AB  - PURPOSE: To estimate the fraction of moving blood in tissue with power Doppler
      ultrasound (US). MATERIALS AND METHODS: Power Doppler US measurements of moving
      scatterers in a flow tube were made as a function of successive dilutions of the
      perfusate. Measurements were normalized relative to the maximum Doppler power in
      the center of the flow tube at the highest concentration and were used to
      calculate the fractional dilution of the perfusate for each run with each
      dilution used to represent increasing amounts of non-moving soft tissue in the
      sample volume. The technique was also applied to two clinical examples. RESULTS:
      Successive dilutions of the perfusate in the flow experiment showed a monotonic,
      linear decrease in the Doppler power as a function of dilution. CONCLUSION: The
      power Doppler US technique has the potential to more accurately estimate
      alterations in blood flow and has the advantage of being a continuous parameter
      that can be depth normalized.

PMID- 7568821
TI  - Recommended specifications for new mammography equipment: report of the ACR-CDC
      Focus Group on mammography equipment.
AB  - The American College of Radiology has published a report that describes desirable
      features for new mammography x-ray units that will contribute to high-quality
      imaging. It encompasses all aspects of x-ray equipment performance including
      mechanical considerations, the x-ray tube focal spot and spectrum, generator
      performance, collimation, scatter rejection, and the automatic exposure control.
      The report is intended to provide guidance to equipment manufacturers and to
      purchasers of mammography systems with regard to basic performance levels that
      should be expected.

PMID- 7568822
TI  - Cerebral infarction in sickle cell disease: transcranial Doppler US versus
      neurologic examination.
AB  - PURPOSE: To evaluate flow velocity measurements in the middle cerebral artery
      (MCA) and/or neurologic examination for detection of cerebral infarction in
      sickle cell disease (SCD). MATERIALS AND METHODS: Twenty-four pediatric patients
      aged 6 1/2-17 years with SCD underwent magnetic resonance (MR) imaging, MR
      angiography, neurologic examination, and transcranial Doppler ultrasonography
      (US). Transcranial Doppler studies were evaluated for maximum flow velocity in
      the right and left MCAs. Combinations of cut-off values were used to determine
      the sensitivity and specificity of transcranial Doppler US for detection of
      infarction. RESULTS: Neurologic examination had 58% sensitivity and 92%
      specificity for cerebral infarction. Maximal flow velocity > 200 cm/sec or < 100
      cm/sec (including no flow) helped identify nine of 12 patients with infarcts
      proved at MR imaging, with only one false-positive result (sensitivity, 75%;
      specificity 92%). The combination of neurologic examination and transcranial
      Doppler US produced 92% sensitivity and 83% specificity for cerebral infarction.
      CONCLUSION: The combination of transcranial Doppler US and neurologic examination
      has potential as a screening technique for infarction in SCD.

PMID- 7568824
TI  - Previously treated, locally recurrent breast cancer: treatment with
      superselective intraarterial chemotherapy.
AB  - PURPOSE: To evaluate the effectiveness of intraarterial infusion chemotherapy
      (IAC) with mitoxantrone hydrochloride in patients with previously treated,
      locally recurrent breast cancer. MATERIALS AND METHODS: Thirty-nine women (aged
      31-82 years) with recurrent breast cancer underwent superselective IAC (25 mg/m2
      mitoxantrone hydrochloride every 24 hours) through the subclavian artery branches
      after heparin administration. The extent of tumor perfusion was monitored with
      computed tomography during the intraarterial administration of contrast medium.
      IAC was repeated one to nine times. Patients had previously undergone radiation
      therapy (n = 39), surgery (n = 20), or systemic chemotherapy (n = 23). RESULTS:
      The overall response rate was 77% (n = 30). Eight patients had complete
      remission. Progression occurred in three patients. Remission was observed in
      cases of lymph node involvement (n = 9). Seven patients are still undergoing
      treatment. Side effects were usually moderate. Nine patients died of systemic
      tumor spread. In 14 patients, distant metastases developed during the first 18
      months of treatment. CONCLUSION: IAC is an effective, well-tolerated therapy in
      patients with locally recurrent breast cancer.

PMID- 7568823
TI  - Craniopharyngioma: treatment in the CT and MR imaging era.
AB  - PURPOSE: To determine optimal treatment in patients with craniopharyngiomas.
      MATERIALS AND METHODS: In 1977-1990, 49 patients (age range, 3-67 years; median
      age, 35 years; 25 female, 24 male) with craniopharyngiomas were examined. Follow
      up was 5-17 years (median, 8 years). Fifteen patients were aged younger than 18
      years. RESULTS: All patients underwent surgical resection. Complete resection was
      achieved in 19. Seven patients underwent additional surgery for recurrent
      disease. Rate of mortality due to surgical complications was 10% (n = 5). Eight
      patients had marked perioperative or long-term morbidity. Twenty-five patients
      judged to have undergone subtotal resection underwent postoperative radiation
      therapy (RT). RT doses were 4,600-6,287 cGy administered in fractions of 180-200
      cGy/d. Actuarial 5-year progression-free survival in patients who underwent
      complete resection was 63% (12 of 19 patients) versus 96% (24 of 25 patients) in
      patients who underwent subtotal resection followed by RT (P = .04). No RT dose
      response was observed. Patient functional status has not been substantially
      affected by adjuvant RT. CONCLUSION: RT achieves excellent tumor control after
      subtotal resection of craniopharyngiomas.

PMID- 7568825
TI  - Head and neck cancer: detection of recurrence with PET and 2-[F-18]fluoro-2-deoxy
      D-glucose.
AB  - PURPOSE: To evaluate positron emission tomography (PET) with 2-[fluorine
      18]fluoro-2-deoxy-D-glucose (FDG) in detection of suspected recurrence of head
      and neck cancer, and to compare visual, static, and kinetic analyses of the
      tracer uptake. MATERIALS AND METHODS: Seventeen dynamic FDG PET studies were
      performed in 15 patients. The images were interpreted visually, and the uptake
      was quantitated as the standardized uptake value (SUV) and as the regional FDG
      metabolic rate. RESULTS: Sensitivity of blinded visual interpretation of the PET
      images for the presence of malignancy was 88% and specificity was 86%. Malignant
      lesions accumulated significantly more FDG than benign lesions (P = .008 for
      SUVs, P = .002 for regional metabolic rates). When maximum uptake of FDG in the
      benign lesions was used as a threshold, the sensitivity of SUV analysis for
      malignancy was 75% and that of regional metabolic rates was 86%. CONCLUSION:
      Detection of recurrent head and neck cancer is feasible with FDG PET.
      Quantitation of FDG uptake assists in correct interpretation of the PET images.

PMID- 7568826
TI  - Hashimoto thyroiditis: correlation of MR imaging signal intensity with
      histopathologic findings and thyroid function test results.
AB  - PURPOSE: To assess the clinical usefulness of magnetic resonance (MR) imaging of
      the thyroid gland in Hashimoto thyroiditis. MATERIALS AND METHODS: Signal
      intensity ratios on spin-echo T1-, proton-density-, and T2-weighted images were
      measured prospectively in 37 patients with Hashimoto thyroiditis (33 women, four
      men; mean age, 51 years) and in 10 patients with thyroid lymphoma (six women,
      four men; mean age, 68 years). Signal intensity ratios were correlated with
      histopathologic findings and thyroid function test results with stepwise
      regression analysis. Diagnosis of lymphoma with signal intensity ratios was
      compared with morphologic diagnosis by using receiver operating characteristic
      curves. RESULTS: A proton-density-weighted signal intensity ratio of 1.54 or
      higher indicated hypothyroidism (R = .445, P = .008; 29% sensitivity [two of
      seven patients]). A T2-weighted signal intensity ratio of 5.08 or higher
      suggested advanced glandular destruction (R = .677, P < .001). Diagnosis by each
      observer was better than diagnosis with signal intensity ratios. CONCLUSION: MR
      imaging results can reflect thyroid function and histopathologic findings in the
      thyroid gland and help discriminate malignant lymphoma from Hashimoto
      thyroiditis.

PMID- 7568827
TI  - Brain tumors: L-[1-C-11]tyrosine PET for visualization and quantification of
      protein synthesis rate.
AB  - PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]
      tyrosine was evaluated in 27 patients with primary and recurrent brain tumors.
      MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET
      (n = 13), with quantification of protein synthesis rate (PSR) and tumor-to
      background ratio. Findings were compared with histologic findings. RESULTS:
      Primary brain tumor was proved in 22 patients histologically, as well as
      metastatic cancer of unknown origin, primary non-Hodgkin lymphoma, meningioma,
      atypical infarction, and vasculitis in one patient each. At PET, 20 of 22 primary
      tumors, the metastasis, and non-Hodgkin lymphoma were correctly depicted. A false
      positive finding was obtained with the infarction, and the meningioma and
      vasculitis were not depicted. The calculated sensitivity was 92%; specificity,
      67%; and accuracy, 89%. There were no statistically significant relationships
      between histologic findings, PSR, and tumor-to-background ratio. CONCLUSION: L-[1
      C-11]-tyrosine is a valid tracer for diagnosis of brain tumors and allowed
      quantification of PSR.

PMID- 7568828
TI  - Hemifacial spasm: three-dimensional MR images in the evaluation of neurovascular
      compression.
AB  - PURPOSE: To assess the diagnostic accuracy of three-dimensional (3D) magnetic
      resonance (MR) images in the preoperative evaluation of hemifacial spasm.
      MATERIALS AND METHODS: In 27 patients with surgically confirmed hemifacial spasm,
      the axial source images from 3D time-of-flight MR angiography were evaluated for
      27 symptomatic sides and 26 asymptomatic sides by three observers in a blinded
      manner for neurovascular compression and identification of compressive vessels.
      RESULTS: Sensitivity was 95% and specificity was 77%. Vascular compression on the
      symptomatic sides could be identified retrospectively in all 27 patients. On the
      asymptomatic sides, vascular compression could be excluded retrospectively in all
      but one patient. In the blinded study, as the mean value of three observers, the
      vertebral artery and posterior inferior cerebellar artery could be identified
      correctly in seven and 7.7 of seven and nine patients, respectively, whereas the
      compressive anterior inferior cerebellar artery was identified correctly in 7.7
      of 16 patients. CONCLUSION: Three-dimensional MR images have a high diagnostic
      accuracy and are useful in the preoperative evaluation of hemifacial spasm.

PMID- 7568830
TI  - Posterior circulation in moyamoya disease: angiographic study.
AB  - PURPOSE: To clarify the angiographic findings of the posterior circulation in
      patients with moyamoya disease. MATERIALS AND METHODS: Seventy-six patients with
      idiopathic moyamoya disease were studied with conventional angiography. The
      angiographic findings were reviewed for steno-occlusive lesions, collateral
      vessels, and aneurysms and compared with the finding of parenchymal lesions on
      computed tomographic and magnetic resonance images. RESULTS: Of 152 posterior
      cerebral arteries (PCAs), 66 (43%) had a stenotic or occluded lesion. The
      frequency of PCA lesions statistically significantly increased with the extent of
      the internal carotid artery (ICA) bifurcation steno-occlusive lesion. As the
      severity of ICA stenosis increased, basal cerebral moyamoya vessels and
      transdural collateral vessels similarly increased in number, but leptomeningeal
      collateral vessels decreased owing to the progressive development of more PCA
      lesions. Cerebral infarctions, ventricular dilatation, and cerebral atrophy were
      found to increase in frequency in patients with steno-occlusive PCA lesions.
      CONCLUSION: Steno-occlusive lesions of the PCA increase in frequency
      proportionally with severity of ICA bifurcation steno-occlusive lesions, so that
      cerebral infarctions increase in frequency with the extent of the PCA lesions.

PMID- 7568829
TI  - Radiologic appearance of the dysembryoplastic neuroepithelial tumor.
AB  - PURPOSE: To evaluate the computed tomographic (CT) and magnetic resonance (MR)
      imaging features of dysembryoplastic neuroepithelial tumor (DNT). MATERIALS AND
      METHODS: Six CT studies (four with contrast material enhancement) and 10 MR
      imaging studies (seven with gadolinium enhancement) obtained in 10 patients with
      a history of seizures and pathologically proved DNT were retrospectively
      reviewed. RESULTS: All tumors were intracortical or subcortical. CT showed a low
      attenuation mass in all cases except one of mixed isoattenuation and low
      attenuation. The DNT had decreased signal intensity on T1-weighted MR images and
      well-demarcated increased signal intensity on T2-weighted images without
      peritumoral edema. Prominent MR imaging features were a gyriform configuration on
      T1- or T2-weighted images in 10 patients (100%), well-demarcated lobular tumor
      margins on T2-weighted images in eight (80%), and a high rate of bone remodeling
      of the adjacent calvaria on MR (60% [n = 6]) and CT (67% [n = 4]) images.
      CONCLUSION: Diagnosis of DNT with imaging modalities alone may be difficult, but
      these radiologic features may aid in differentiating DNT from other gliomas.

PMID- 7568831
TI  - Lumbosacral spine: early and delayed MR imaging after administration of an
      expanded dose of gadopentetate dimeglumine in healthy, asymptomatic subjects.
AB  - PURPOSE: To determine normal magnetic resonance (MR) imaging enhancement
      characteristics of the lumbosacral spine after intravenous administration of an
      expanded dose of gadopentetate dimeglumine. MATERIALS AND METHODS: T1-weighted MR
      images of the lumbosacral spine were acquired before and after injection of 0.3
      mmol/kg gadopentetate dimeglumine in 12 healthy subjects (eight men, four women;
      age range, 22-57 years). RESULTS: In 10 (91%) of the 11 subjects who completed
      the investigation, multifocal linear enhancement within the thecal sac that
      generally extended from the conus to the nerve-root sheaths was demonstrated. In
      all cases, enhancement was seen in the facet joints and the intervertebral disks
      parallel to the vertebral end-plates. CONCLUSION: After an expanded dose of
      intravenous gadopentetate dimeglumine, multiple intrathecal and extrathecal
      structures were enhanced. Recognition of normal enhancement patterns after an
      expanded gadopentetate dimeglumine dose is important because such enhancement
      after routine injection of 0.1 mmol/kg gadopentetate dimeglumine is often thought
      to indicate disease.

PMID- 7568832
TI  - Positional variation in the Whitaker test.
AB  - PURPOSE: To describe positional variation in the outcome of the Whitaker test.
      MATERIALS AND METHODS: The authors retrospectively reviewed the cases of six
      patients in whom the pressure gradient during Whitaker testing varied by at least
      10 cm of water and changed from normal ( < or = 13 cm of water) to abnormal ( >
      13 cm of water) when patients were placed in different positions. RESULTS: Four
      patients had obstruction only in nonstandard positions. All had intermittent
      symptoms, and three had ureteral kinks at fluoroscopy. Two patients with ileal
      conduits had abnormal results in the standard position but normal results at
      repositioning related to compression of the conduits (seen as conduit distention
      at fluoroscopy). All six had undergone urinary tract surgery. Gradient
      differences with positional change ranged from 10 to > 38 cm of water.
      CONCLUSIONS: Whitaker testing in different positions may help identify
      intermittent obstructions that might otherwise go undetected or prevent
      inappropriate diagnosis of obstruction. Intermittent or unexplained symptoms,
      tortuous ureters, malpositioned kidneys, or previous surgery are indications for
      provocative positional testing.

PMID- 7568833
TI  - Hamstring injuries: radiographic, conventional tomographic, CT, and MR imaging
      characteristics.
AB  - PURPOSE: To review experience with the imaging features of hamstring injuries.
      MATERIALS AND METHODS: Imaging findings in 18 male and four female patients with
      clinically proved hamstring injuries were reviewed. The patients' ages ranged
      from 13 to 61 years (mean, 26 years). Radiography, conventional tomography,
      computed tomography (CT), and magnetic resonance (MR) imaging were performed.
      RESULTS: Plain radiographs obtained less than 1 week after injury were normal or
      showed avulsion of an ischial apophysis. Plain radiographs and conventional
      tomograms obtained more than 1 week but less than 3 months after injury were
      confusing, because callus and osteolysis were present. CT helped identify a
      healing avulsion of an ischial apophysis. MR imaging was helpful no matter how
      long after the injury it was performed. It provided a means to evaluate muscle,
      tendon, and bone. CONCLUSION: Familiarity with the variable appearance of
      hamstring injuries over time and with different modalities facilitates accurate
      characterization.

PMID- 7568834
TI  - MR imaging in evaluation of suspected hip fracture: frequency of unsuspected bone
      and soft-tissue injury.
AB  - PURPOSE: To determine the frequency of unsuspected pelvic fracture and soft
      tissue injury in patients referred for magnetic resonance (MR) imaging for
      possible radiographically occult hip fracture. MATERIALS AND METHODS: Seventy
      patients with symptoms of possible hip fracture but negative plain radiographs
      were evaluated with MR imaging. Large-field-of-view T1-weighted coronal images
      were obtained, and additional T2-weighted or short inversion time inversion
      recovery (STIR) sequences were used. The number of soft-tissue and bone injuries
      identified was recorded. RESULTS: Eighty percent of patients had bone or soft
      tissue abnormalities. Occult femoral and pelvic fractures were demonstrated in
      37% and 23% of patients, respectively. Soft-tissue abnormalities were noted in
      74% of patients. When a proximal femoral fracture was not present, MR imaging
      revealed a 27% frequency of occult pelvic fracture and a 50% frequency of bone or
      soft-tissue abnormality. CONCLUSION: A high prevalence of occult pelvic fracture
      and soft-tissue injury may be identified with MR studies designed to evaluate
      occult hip fracture when large-field-of-view T1-weighted coronal sequences are
      combined with T2-weighted or STIR sequences.

PMID- 7568836
TI  - Normalized average glandular dose in magnification mammography.
AB  - PURPOSE: To evaluate the normalized average glandular dose (the average glandular
      dose per unit entrance skin exposure) in magnification mammography. MATERIALS AND
      METHODS: Photon transport in the breast was simulated by using Monte Carlo
      methods. A semielliptical cylinder containing glandular and adipose tissue was
      used to simulate the breast. Measured mammography spectra for a molybdenum target
      molybdenum filter unit were utilized. The normalized average glandular dose was
      calculated as a function of half-value layer, tube voltage, breast thickness, and
      breast composition for typical magnification geometries. RESULTS: The normalized
      average glandular dose in magnification mammography is 7%-25% lower than that
      with the contact (nonmagnification) technique because of the effects of partial
      irradiation, smaller field size, and greater percentage depth dose gradient at
      the reduced source-to-skin distance. CONCLUSION: The normalized average glandular
      dose in magnification mammography is lower than that in contact mammography. The
      average glandular dose in magnification mammography, however, is still
      substantially greater due to the two to three times greater entrance skin
      exposure.

PMID- 7568835
TI  - Acute traumatic tears of the rotator cuff: value of sonography.
AB  - PURPOSE: To determine the value of sonography in the evaluation of acute
      traumatic tears of the rotator cuff. MATERIALS AND METHODS: Preoperative
      sonography was performed within 3 weeks of trauma in 184 patients, 98 of whom
      underwent surgery. The rotator cuff tears were preoperatively classified as
      partial-thickness tears or as small, large, or massive full-thickness tears.
      Sonographic findings were correlated with surgical findings (n = 70) and
      arthroscopic inspection (n = 28). RESULTS: Adequate examination was possible in
      163 (88%) of 184 patients. Sonography demonstrated 42 (91%) of 46 full-thickness
      tears and seven (78%) of nine partial-thickness tears. Sonography showed more
      extensive tears than were found at surgery in four (4%) of 98 patients and less
      extensive tears in seven (7%) of 98 patients. Sonographic patterns were a defect
      (31 [63%] of 49 tears), focal thinning (10 [21%] of 49 tears), and
      nonvisualization (eight [16%] of 49 tears). CONCLUSION: Sonography is useful in
      the evaluation of acute shoulder trauma when a rotator cuff tear is suspected and
      findings at plain radiography are negative.

PMID- 7568837
TI  - Synovial fluid in the hindfoot and ankle: detection of amount and distribution
      with US.
AB  - PURPOSE: To determine the amount and distribution of synovial fluid detectable
      with ultrasonography (US) of the hindfoot and ankle in asymptomatic volunteers.
      MATERIALS AND METHODS: US was performed with a 7.5- or 10-MHz linear transducer
      of 60 hindfeet and ankles in 30 volunteers. Presence and amount of fluid were
      assessed in the ankle joint recesses, adjacent bursae, and tendon sheaths.
      Symmetry of bilateral fluid was evaluated. RESULTS: Fluid was detected in the
      anterior recess in 20 ankles (bilaterally in eight volunteers), retrocalcaneal
      bursa in 30 ankles (bilaterally in 12 volunteers), posterior tibial tendon sheath
      in 46 ankles (bilaterally in 19 volunteers), and common peroneal tendon sheath in
      seven ankles (bilaterally in three volunteers). No fluid was seen in the
      posterior recess. On average, symmetry was present for only the retrocalcaneal
      bursal and peroneal tendon sheath fluid. CONCLUSION: US of the hindfoot and ankle
      commonly depicts articular, bursal, and tendon sheath fluid in asymptomatic
      volunteers. The presence of fluid in these locations, even when unilateral or
      asymmetric, does not necessarily imply underlying abnormality.

PMID- 7568838
TI  - Pyomyositis: characteristics at CT and MR imaging.
AB  - PURPOSE: To establish imaging criteria for pyomyositis (PM). MATERIALS AND
      METHODS: Twenty-seven computed tomographic (CT) scans and 11 magnetic resonance
      (MR) images obtained in 32 patients with PM were reviewed. Images in 10 patients
      with PM and 16 with soft-tissue masses were evaluated blindly. RESULTS: At CT,
      all 27 patients had muscle enlargement with heterogeneous attenuation; 26
      patients had a focal fluid collection, with rim enhancement in all 18 patients
      who underwent contrast material-enhanced CT. Twenty-four patients had cellulitis.
      At MR imaging, all 11 patients had both a subtle increase in signal intensity in
      the affected muscle(s) on T1-weighted images and cellulitis. Nine patients had a
      focal fluid collection, which had high signal intensity and a hypointense rim on
      T2-weighted images. In six patients, a rim of increased signal intensity was seen
      around the collection on T1-weighted images. Six gadolinium-enhanced examinations
      demonstrated rim enhancement. Eight patients had fluid in the distal joint. All
      patients with PM were correctly identified when evaluated with the control
      subjects; however, there were four false-positive results. CONCLUSION: CT and MR
      imaging can help characterize changes that are suspicious for PM.

PMID- 7568839
TI  - Three-compartment wrist arthrography: direct comparison of digital subtraction
      with nonsubtraction images.
AB  - PURPOSE: To determine the diagnostic value of digital subtraction and
      fluoroscopic spot images in wrist arthrography, alone and in combination.
      MATERIALS AND METHODS: Randomized selective bilateral three-compartment wrist
      arthrography was performed in 64 patients. The fluoroscopic spot and digital
      subtraction images were read separately by two radiologists without knowledge of
      the clinical data. RESULTS: One hundred twenty communicating defects were found
      in 69 wrists in 42 patients. Fluoroscopic spot radiographs alone depicted defects
      in all 69 wrists, but precise localization was not possible in 10 defects.
      Subtraction images alone demonstrated 59 defects. The defects not seen with
      digital subtraction imaging were identified after wrist motion. Digital
      subtraction images demonstrated defects earlier during the joint injection and
      demonstrated the exact site of the 10 defects not localized on the nonsubtracted
      images. CONCLUSION: Digital subtraction and fluoroscopic spot images are
      complementary in wrist arthrography and, when used in combination, increase the
      ability to localize the sites of defects, although the value added by the
      subtraction technique is small.

PMID- 7568841
TI  - Ulnar collateral ligament injury in the throwing athlete: evaluation with saline
      enhanced MR arthrography.
AB  - PURPOSE: To determine whether magnetic resonance (MR) arthrography of the elbow
      can demonstrate precisely an ulnar collateral ligament (UCL) abnormality in the
      throwing athlete. MATERIALS AND METHODS: Forty college-level and professional
      throwing athletes (age range, 18-40 years) underwent saline-enhanced MR
      arthrography of their injured elbows. MR findings were compared with the surgical
      findings. RESULTS: Saline-enhanced MR arthrography was positive in 24 of 26
      individuals with UCL tear confirmed at the time of surgery. Eighteen (95%) of 19
      complete UCL tears and six (86%) of seven partial UCL tears were diagnosed with
      MR arthrography. Two false-negative findings and no false-positive findings were
      obtained. CONCLUSION: Saline-enhanced MR arthrography of the elbow is a new
      application of a previously described technique used in the shoulder. It is
      useful for demonstration of subtle and gross UCL abnormalities in the throwing
      athlete.

PMID- 7568840
TI  - Echotexture of peripheral nerves: correlation between US and histologic findings
      and criteria to differentiate tendons.
AB  - PURPOSE: To correlate the histologic structure and echotexture of peripheral
      nerves and verify if ultrasound (US) findings can be used to differentiate nerve
      from tendon. MATERIALS AND METHODS: In an in vitro study, the echotexture of
      normal peripheral nerves was correlated with the histologic findings. In an in
      vivo study, US was used to differentiate median nerve from flexor pollicis longus
      tendon in healthy volunteers (12 male and eight female subjects 7-68 years of
      age; mean age, 35 years). RESULTS: US examination of the peripheral nerve
      specimens showed hypoechoic areas separated by hyperechoic bands. The hypoechoic
      areas corresponded to neuronal fascicles at histologic examination. This
      fascicular pattern was clear in all median and ulnar nerves, 15 of 20 vagus
      nerves, and 19 of 20 sciatic nerves in the volunteers but not in recurrent
      laryngeal nerves. CONCLUSION: Peripheral nerves have a typical US pattern that
      correlates with histologic structure and facilitates differentiation between
      nerves and tendons.

PMID- 7568842
TI  - Acute myeloid leukemia: lack of predictive value of sequential quantitative MR
      imaging during treatment.
AB  - PURPOSE: To assess the use of magnetic resonance (MR) imaging in monitoring
      treatment response in patients with acute myeloid leukemia (AML). MATERIALS AND
      METHODS: Bulk T1 and T2 were determined with at least four MR imaging
      examinations (strictly timed) during the first 6 weeks of treatment in 29
      patients with AML (age range, 16-75 years; 15 female, and 14 male). Bulk T1 and
      T2 in responder (n = 22) and nonresponder (n = 7) patients were compared.
      RESULTS: Relative to pretreatment bulk T1 values, bulk T1 had increased a mean of
      11% at week 1 and had decreased a mean of 7% and 39% at weeks 2 and 6,
      respectively. Values in nonresponder patients were not statistically
      significantly different (+11%, -14%, -38%). CONCLUSION: MR imaging of lumbar bone
      marrow in patients with AML demonstrated statistically significant changes in
      bulk T1 during treatment that correlated with changes in cellularity. However,
      neither the early increase in bulk T1 nor the rate or magnitude of the subsequent
      decrease in bulk T1 were indicative of a positive response to treatment.

PMID- 7568843
TI  - Malignant acetabular osteolyses: percutaneous injection of acrylic bone cement.
AB  - Percutaneous osteoplasty with acrylic bone cement was performed in 12 acetabular
      osteolytic lesions in 11 patients with inoperable metastases (n = 8) and myeloma
      (n = 3). Complementary radiation therapy was started 15-30 days after injection
      in each case. Pain diminished within hours to 4 days in nine patients, and
      walking improved in each patient within 1-5 days. Five patients died during the
      follow-up period. Clinical improvement was maintained in all but two patients.

PMID- 7568844
TI  - Synchronization device for electrocardiography-gated echo-planar imaging.
AB  - An electrocardiography (ECG) synchronization technique allowed triggering of 1.5
      T echo-planar acquisitions of the heart, with high gradient slew rates. In 51
      volunteers (37 men and 14 women, aged 21-48 years), the ECG signal was amplified,
      filtered, and converted into an optical signal directly above the heart and was
      transmitted optically outside the bore. Reliable and artifact-free ECG tracings
      were obtained in all cases, regardless of the gradient switching speed.

PMID- 7568846
TI  - Bilateral lower-extremity US for deep venous thrombosis.

PMID- 7568848
TI  - Increased scan pitch for vascular and thoracic spiral CT.

PMID- 7568847
TI  - Chronic hepatic failure and T1 shortening of the basal ganglia.

PMID- 7568845
TI  - MR imaging in the diagnosis of aortic dissection.

PMID- 7568849
TI  - "Peripheral washout" sign: terminology does not reflect the exact mechanism of
      enhancement.

PMID- 7568850
TI  - Benign and malignant breast lesions: differentiation with echo-planar MR imaging.
AB  - PURPOSE: To quantify dynamic enhancement of breast lesions with echo-planar and
      conventional magnetic resonance (MR) imaging, to correlate these data with
      histologic findings and vessel density, and to evaluate MATERIALS AND METHODS:
      Twenty female patients with 22 breast lesions underwent conventional and MR echo
      planar imaging T1 values, change in gadopentetate dimeglumine concentration, and
      extraction-flow products were calculated with echo-planar imaging data and were
      correlated with histologic findings and microvessel density. RESULTS: T1 values
      of cancers were not statistically significantly shorter. Cancers had more rapid
      uptake and higher extraction-flow products (P < .02). Sensitivity was 86% and
      specificity was 93% for diagnosis of malignancy. Microvessel density was higher
      for malignant lesions (P < .02) with an overall positive (not statistically
      significant) correlation between extraction-flow product and microvessel density.
      CONCLUSION: Echo-planar imaging appears promising for quantification of breast
      lesion enhancement. Microvessel data indicate that tumor angiogenesis affects
      enhancement.

PMID- 7568851
TI  - Automated quantification of color Doppler signals: a preliminary study in breast
      tumors.
AB  - PURPOSE: To quantify color Doppler (CD) signals reflected by breast lesions to
      improve differential diagnosis and serial comparisons. MATERIALS AND METHODS:
      Frame-grabbed color-capture scans were remapped to original velocities on a pixel
      by-pixel basis for statistical analysis. Total CD area and its percentage, peak
      and mean velocities, standard deviation of velocity, and integral CD velocity and
      its percentage were calculated. These indexes were applied to scans of 44
      cancers, 16 fibroadenomas, and 14 benign breast changes in 74 patients. RESULTS:
      With the region of interest confined to the lesion and a 5-mm margin, no CD
      signals were reflected by the benign breast changes. All carcinomas and 12
      fibroadenomas (those that were vascular) reflected CD signals, and, except for
      mean and peak velocity, all scores for cancers were significantly higher than for
      fibroadenomas (P < .0001). Integral CD velocity was the best discriminator, with
      no overlap between carcinomas (range, 1,128-50,228 cm3/sec) and fibroadenomas
      (range, 0-1,027 cm3/sec). CONCLUSION: Automatic CD quantification improved
      differential diagnosis of breast masses.

PMID- 7568852
TI  - Single- and double- lumen silicone breast implant integrity: prospective
      evaluation of MR and US criteria.
AB  - PURPOSE: To evaluate the accuracy of magnetic resonance (MR) and ultrasound (US)
      criteria for breast implant integrity. MATERIALS AND METHODS: One hundred twenty
      two single-lumen silicone breast implants and 22 bilumen implants were evaluated
      with surface coil MR imaging and US and surgically removed. MR criteria for
      implant failure were a collapsed implant shell ("linguine sign"), foci of
      silicone outside the shell ("noose sign"), and extracapsular gel, US criteria
      were collapsed shell, low-level echoes within the gel, and "snowstorm" echoes of
      extracapsular silicone. RESULTS: Among single-lumen implants, MR imaging depicted
      39 of 40 ruptures, 14 of 28 with minimal leakage; 49 of 54 intact implants were
      correctly interpreted. US depicted 26 of 40 ruptured implants, four of 28 with
      minimal leakage, and 30 of 54 intact implants. Among bilumen implants, MR imaging
      depicted four of five implants with rupture of both lumina and nine of 10 as
      intact; US depicted one rupture and helped identify two of 10 as intact.
      Mammography accurately depicted the status of 29 of 30 bilumen implants with MR
      imaging correlation. CONCLUSION: MR imaging depicts implant integrity more
      accurately than US; neither method reliably depicts minimal leakage with shell
      collapse. Mammography is useful in screening bilumen implant integrity.

PMID- 7568853
TI  - Intrathoracic lymphoproliferative disorders in the immunocompromised patient: CT
      findings.
AB  - PURPOSE: To assess the computed tomographic (CT) findings of intrathoracic
      lymphoproliferative disorders in the immunocompromised patient. MATERIALS AND
      METHODS: The authors retrospectively reviewed CT scans of the chest in 18
      consecutive patients with pathologically proved intrathoracic lymphoproliferative
      disorders. Twelve patients had the acquired immunodeficiency syndrome (AIDS), and
      six were receiving immunosuppressive therapy. Final diagnosis included AIDS
      related diffuse lymphoid hyperplasia (n = 1), lymphocytic interstitial pneumonia
      (LIP) (n = 3), posttransplantation lymphoproliferative disorders (PTLDs) (n = 4),
      and lymphoma (n = 10). RESULTS: Diffuse areas of ground-glass attenuation were
      found in the patient with lymphoid hyperplasia and the three patients with LIP.
      The four patients with PTLDs had multiple, well-circumscribed pulmonary nodules,
      and nodules in three of the four patients had a halo of ground-glass attenuation.
      Nine of the 10 patients with lymphoma had well-circumscribed nodules or nodules
      with consolidation. Mediastinal lymph node enlargement was present in two
      patients with PTLDs and three patients with lymphoma. CONCLUSION: The
      intrathoracic CT findings of lymphoproliferative disorders appear to be similar
      in immunocompromised patients with and without AIDS and are usually extranodal.

PMID- 7568854
TI  - Is the Mammography Quality Standards Act worth the cost?

PMID- 7568855
TI  - Unusual lymphoproliferative disorders in nine adults with HIV or AIDS: CT and
      pathologic findings.
AB  - PURPOSE: To identify characteristic computed tomographic (CT) findings in unusual
      pulmonary lymphoproliferative disorders seen in adults with the human
      immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
      MATERIALS AND METHODS: The authors retrospectively reviewed the CT scans and
      pathologic specimens from nine patients with pulmonary lymphoproliferative
      disorders. CT scans were evaluated for nodules, reticulation, areas of ground
      glass attenuation, consolidation, and bronchial disease. Changes seen in
      pathologic specimens were classified as consistent with classic lymphocytic
      interstitial pneumonitis (LIP), mucosa-associated lymphoid tissue lymphoma
      (MALTOMA), or atypical lymphoproliferative disorder (ALD). Immunopathologic
      results were reviewed when available. RESULTS: Eight patients had AIDS. Five
      patients had classic LIP. One patient had MALTOMA, and three patients had ALD.
      Altogether, 2-4-mm-diameter nodules were the predominant CT finding in eight
      patients; these were peribronchovascular in four patients. The presence of
      interstitial nodules correlated with the pathologic finding of nodular disease in
      seven patients. CONCLUSION: Familiarity with these AIDS-related disorders and
      their CT appearance should assist in the differential diagnosis.

PMID- 7568856
TI  - Bacillary angiomatosis in patients with AIDS: multiorgan imaging findings.
AB  - PURPOSE: To describe the varied clinical manifestations and imaging findings
      encountered in bacillary angiomatosis, an infectious complication of the acquired
      immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Clinical, imaging, and
      histopathologic findings in nine men (aged 26-50 years) with AIDS and bacillary
      angiomatosis were described. This condition often manifests as vascular skin
      lesions that resemble those of Kaposi sarcoma, fever, and anemia and is due to
      infection with Bartonella (Rochalimaea) henselae. RESULTS: Common imaging
      findings included lung nodules, mediastinal adenopathy, peripheral adenopathy,
      pleural effusions, ascites, abdominal adenopathy, soft-tissue masses, and low
      attenuation lesions in the liver and/or spleen. Most notably, nodes and soft
      tissue lesions were dramatically enhanced with injection of contrast material,
      which is presumably because the lesions are composed to a large extent of well
      formed capillaries. CONCLUSION: Bacillary angiomatosis, a treatable infection,
      should be considered in patients with AIDS, particularly when Kaposi sarcoma is
      suspected clinically.

PMID- 7568857
TI  - Spiral CT of the chest: comparison of cine and film-based viewing.
AB  - PURPOSE: To determine radiologists' ability to find lung nodules on spiral
      computed tomographic (CT) scans of the chest with both rapid sequential (cine)
      and conventional film-based viewing. MATERIALS AND METHODS: Eight radiologists
      searched for lung nodules on spiral CT images (10-mm collimation, 10 mm/sec table
      speed) presented in two formats. Cine viewing was performed at a computer work
      station; sections were viewed in 2-mm increments at frame rates up to 10 frames
      per second. Film-based viewing of images from a laser printer was performed with
      a lightbox; sections were viewed at 4-mm increments. Eight 3-5-mm-diameter
      simulated nodules were superimposed on each of five normal CT scans. RESULTS:
      Radiologists found a higher fraction of nodules with the cine presentation than
      with film (mean, 0.69 +/- 0.02 [standard error] versus 0.58 +/- 0.03,
      respectively [P = .006]). Diameter thresholds for nodule detection (50% correctly
      localized) were 3.3 and 3.5 mm, respectively. CONCLUSION: Cine viewing of spiral
      CT images of the chest improved radiologists' ability to detect nodules.

PMID- 7568858
TI  - Diagnostic imaging of mesenteric infarction.
AB  - PURPOSE: To determine the value of diagnostic imaging in the management of
      mesenteric infarction. MATERIALS AND METHODS: Within 8 years, 54 patients with
      mesenteric infarction underwent diagnostic imaging before surgery, including
      plain radiography (n = 45), ultrasound (US) (n = 29), small bowel follow-through
      examination (n = 7), colon enema study (n = 7), angiography (n = 16), and
      computed tomography (CT) (n = 22). Clinical course, laboratory values, and
      imaging findings were considered in diagnosis. RESULTS: Radiography and US
      allowed correct diagnoses in five of 18 cases (28%). Only one of 14 fluoroscopic
      examinations contributed to diagnosis. Fourteen of 16 angiography studies
      (sensitivity, 87.5%) and 18 of 22 CT examinations (82%) were correct. The
      difference in sensitivity between CT and angiography was not significant (P >
      .05). CONCLUSION: CT and angiography are highly sensitive, but CT can also be
      used to rule out other causes of acute abdomen. Careful evaluation of patient
      history and clinical situation should lead to suspicion of mesenteric ischemia
      and early indication for CT.

PMID- 7568859
TI  - Hepatic spiral CT: reduction of dose of intravenous contrast material.
AB  - PURPOSE: To assess the potential for reduction of contrast material dose in
      hepatic spiral computed tomography (CT). MATERIALS AND METHODS: Four hundred
      eighty-seven outpatients were randomized prospectively into nine biphasic and
      eight uniphasic injection protocols: 75, 100, or 125 mL of 240, 300, or 350 mg of
      iodine per milliliter of iohexol (18-44 grams of iodine). Protocols were compared
      according to the maximum hepatic enhancement (MAX) and the contrast enhancement
      index (CEI). RESULTS: Uniphasic injection was superior to biphasic injection for
      all protocols. No statistically significant difference in contrast enhancement
      was present for 38-44 grams of iodine with the uniphasic technique. Adequate
      enhancement thresholds (MAX > 50 HU, CEI at 30 HU > 300 HU x sec) were exceeded
      in more than 70% of heavy patients ( > 183 lb [83 kg]) with uniphasic injection
      of 38 g. For thin patients ( < 183 lb [83 kg]), uniphasic injection of 26 g
      produced adequate enhancement. CONCLUSION: Contrast material dose may be reduced
      by up to 40% in thin patients undergoing hepatic spiral CT after uniphasic
      injection of contrast material; this may result in substantial cost savings.

PMID- 7568862
TI  - 81st Radiological Society of North America scientific assembly and annual
      meeting. 1995.

PMID- 7568860
TI  - Hepatic helical CT: effect of reduction of iodine dose of intravenous contrast
      material on hepatic contrast enhancement.
AB  - PURPOSE: To evaluate the effect of a reduction in iodine dose by altering volume
      and/or concentration of contrast material on hepatic contrast enhancement (HCE)
      values during hepatic helical computed tomography (CT). MATERIALS AND METHODS:
      One hundred eleven patients were randomized into four contrast material protocols
      according to concentration (in milligrams of iodine per milliliter)/volume (in
      milliliters)/grams of iodine: group 1, ioversol, 320/150/48; group 2, ioversol,
      320/100/32; group 3, iohexol, 300/150/45; group 4, ioversol, 300/100/30. Helical
      CT protocols were identical for the four groups. Time-attenuation curves were
      constructed; the mean HCE, contrast enhancement index (CEI), and optimal liver
      scanning interval (OLSI) were calculated; and the results were compared
      statistically. RESULTS;: Time-attenuation curves, mean HCE, CEI, and OLSI of
      groups 1 and 3 were significantly superior to those for groups 2 and 4. Decrease
      in volume from 150 to 100 mliters decreased mean HCE by 27%, CEI by 69%, and OLSI
      from 80%-100% to 0%-43% at threshold levels of 40-60 HU. CONCLUSION: Decrease in
      iodine dose from 45-48 g to 30-32 g significantly decreases all HCE values, which
      potentially decreases detection of focal hypovascular hepatic lesions.

PMID- 7568863
TI  - [Retrospective study of circulation of human rotavirus electropherotypes in the
      city of Cordoba, Argentina, 1979-1989].
AB  - A retrospective survey was carried out to determine the occurrence and
      circulation of different human rotavirus electropherotypes. Stool specimens were
      collected from children under four years old admitted to pediatric health
      services of Cordoba city, Argentina, from January 1979 to December 1989.
      Polyacrylamide gel electrophoresis followed by silver staining was employed for
      rotavirus detection. Of 1839 faecal samples 228 (13.9%) were positive for
      rotavirus. Examination of the electrophoretic patterns allowed us to identify 16
      different electropherotypes (EPT), eleven with a long pattern (82.2%) and 5 with
      a short one (18.8%). The L 79-5 (31.4%), L 84-8 (22.1%), S 79-7 (11.9%) and S 86
      10 (4.4%) were the predominant EPT, persisting between 4 and 6 years in the
      community. A cocirculation of more than one electropherotype was observed
      annually. The results provide information concerning the number of different
      electropherotypes of human rotavirus in the community, the sequential pattern of
      electropherotype appearance and the length of time for which an electropherotype
      may persist.

PMID- 7568861
TI  - Discomfort during double-contrast barium enema examination: a placebo-controlled
      double-blind evaluation of the effect of glucagon and diazepam.
AB  - PURPOSE: To evaluate the effectiveness of glucagon and diazepam as compared with
      placebo in decreasing abdominal discomfort in patients during double-contrast
      barium enema examination. MATERIALS AND METHODS: Thirty-six men (n = 9) and women
      (n = 27) aged 21-62 years with "a lot or terrible discomfort" during double
      contrast barium enema examination were randomized into double-blind groups of 12
      patients each at the onset of examination. Each group received a placebo,
      glucagon (1 mg), or diazepam (5 mg) intravenously. Discomfort was scored on a
      four-point scale by the patients. RESULTS: Repeated measures analysis of variance
      findings indicated that those who received an active drug reported significantly
      (P = .001) greater relief of discomfort. Discomfort scores improved, on average,
      2.2 in the glucagon, 2.0 in the diazepam, and 1.2 in the placebo groups. Colonic
      spasm did not correlate with abdominal discomfort. CONCLUSION: Discomfort during
      double-contrast barium enema examination can be statistically significantly
      diminished with a hypotonic agent or a sedative.

PMID- 7568864
TI  - [Effect of carbon and nitrogen sources on the cellulolytic activity of Trametes
      trogii].
AB  - Trametes trogii was grown in a liquid synthetic medium containing different
      carbon and nitrogen sources. Enzymatic activities of cellulases (endoglucanase,
      exoglucanase and beta-glucosidase) were measured in culture supernatants. Organic
      nitrogen sources were the most favourable for growth and cellulase production.
      Increasing nitrogen concentrations also increased cellulase production. Among
      carbon sources, crystalline cellulose, cellobiose and a mixture of
      carboxymethylcellulose and cellobiose induced maximal endoglucanase production.
      The optimal concentration of the carbon source was 10 g/l.

PMID- 7568865
TI  - [Bacteria of the genus Bacillus in chicken carcasses and hamburgers].
AB  - The incidence of mesophilic aerobic sporulate bacteria in chicken carcasses and
      hamburgers was studied and the species of isolated sporulate bacteria were
      identified. Forty seven eviscerated carcasses from a processing plant of Entre
      Rios province (Argentina) were analyzed together with fifty samples of hamburgers
      from two supermarkets of Santa Fe city. All carcasses resulted in contamination
      with aerobic mesophilic bacteria in the range from 6 x 10(3) to 1.2 x 10(6)
      CFU/ml liquid washed, and 94% them with sporulate bacteria, the threshold being
      under 100 CFU/ml (Figure 1). Hamburgers from both places resulted with aerobic
      mesophilic bacteria in 100% of the cases, in the range of 1 x 10(5)-3.3 x 10(6)
      CFU/g for supermarket A and 2.2 x 10(5) to 1.7 x 10(7) CFU/g for supermarket B;
      the incidence of sporulate bacteria was between 4.3 x 10(2) and 1.2 x 10(4) CFU/g
      for A, while the range for B was 6.2 x 10(2) and 3.8 x 10(4) CFU/g (Figure 2).
      Two hundred and fourteen Bacillus Genus strains were isolated and purified from
      the carcasses and five hundred and ninety five from hamburgers. B. subtilis and
      B. megaterium were most involved in carcasses; while B. licheniformis, B.
      subtilis and B. pumilus were in hamburgers from supermarket A and B. subtilis and
      B. pumilus were found in supermarket B (Table 1). The presence of B. cereus was
      also found, although in low levels, in all the samples (Table 1). Pollution
      levels with aerobic mesophilic bacteria are high in both kinds of
      samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568867
TI  - [Susceptibility of picornaviruses++ to an antiviral of plant origin (meliacin)].
AB  - Meliacine, a peptide associated with antiviral activity isolated from the high
      plant Melia azedarach L (MA) inhibits the replication of different strains of
      foot and mouth disease virus (FMDV) and poliovirus in BHK-21 or Vero cells,
      respectively, infected at a multiplicity of infection (m.o.i.) of 1. A leaf
      extract of MA, containing meliacine was added to the culture medium after virus
      adsorption and maintained up to virus harvest (18 hs). FMDV O1 Campos and O69
      strains showed 60% and 52% inhibition, respectively. A24 and A87 strains proved
      to be inhibited more than 90%, and the C3 Resende and O1 Case-ros strains were
      not sensitive to the extract. Regarding the three types of poliovirus, the most
      susceptible one was type 1 (84%). Types 2 and 3 were inhibited only 69% and 32%,
      respectively. Treatment of the cells with the antiviral for 24 hours before
      infection (pretreatment), was not effective for the two above mentioned viruses.
      Since the extract of MA is very active against other RNA viruses (i.e. vesicular
      stomatitis virus), the susceptibility of FMDV strain O1 Campos and poliovirus
      type 3 was tested using lower m.o.i. The results showed that MA produced an
      inhibition of viral replication of 99% at a m.o.i. of 0.001 in both cases. These
      results suggest that picornaviruses are also susceptible to MA. However, to
      demonstrate its antiviral effect it is necessary to slow down the rate of virus
      cell killing by reducing the m.o.i.

PMID- 7568866
TI  - [Influence] of enzymatic treatment on Junin virus--Vero cells interaction].
AB  - The chemical nature of cellular structures involved in the attachment of Junin
      virus (wild type XJC13 and host range mutant Cl 67) to Vero cells was
      investigated. Enzyme treatment of cells before virus infection indicated that
      whereas lipids are not directly involved in virus attachment, cellular proteins
      play a significant role in early interaction with JV. Moreover aromatic residues,
      leucine and basic amino acid seem to actively participate in this interaction
      with different affinity for the assayed strains.

PMID- 7568868
TI  - [Lymphocytic migration and related adhesion molecules].

PMID- 7568869
TI  - Kainate-induced changes in gene expression in the rat hippocampus.

PMID- 7568872
TI  - Growth factors in the CNS and their effects on oligodendroglia.

PMID- 7568870
TI  - Mechanisms of neuronal plasticity as analyzed at the single cell level.
AB  - This chapter has highlighted how correlates of neuronal plasticity such as
      electrophysiological responsiveness and changes in gene expression may be
      examined in defined CNS regions as well as in single cells. The ability to
      simultaneously measure the mRNA levels for hundreds of different genes, to clone
      novel genes, and to characterize the physiology and morphology of the cell
      promises to provide insight into molecular mechanisms of plasticity. The
      importance of understanding how one gene product changes relative to another
      (coordinated changes) as well as subcellular distribution of mRNAs cannot be
      overstated. It is only through an analysis of both the molecular and cellular
      processes associated with plasticity that a thorough understanding of the
      mechanisms of neuronal plasticity can be gained.

PMID- 7568871
TI  - Plasticity and commitment in the developing cerebral cortex.

PMID- 7568875
TI  - The differentiation and function of the touch receptor neurons of Caenorhabditis
      elegans.
AB  - We have identified several genes required for four aspects of the differentiation
      and function of a set of six touch receptor neurons in the nematode
      Caenorhabditis elegans: (1) the generation of appropriate cells; (2) the
      specification of those cells to differentiate as touch receptors; (3) the
      maintenance of the differentiated state; and (4) the expression of products need
      for the cell function. Three major conclusions about the development of the touch
      cells arise from the analysis of these genes. First, specification of cell fate
      is a combinatorial process. At least seven genes, none of which are expressed
      solely in these cells, are needed to restrict the expression of touch-cell
      features in the appropriate cells. Second, the differentiated state must also be
      maintained. Three genes appear necessary for this maintenance function. Third,
      regulation of development is not strictly linear; at least one gene is needed at
      more than one stage of differentiation. In addition to being interested in the
      factor that determine cell fate, we are also interested in understanding the
      molecular basis of mechanosensory transduction. The function class genes are
      particularly important in this regard, especially those that when mutant result
      in the loss of the touch response without producing any obvious morphological
      defects in the touch cells.

PMID- 7568874
TI  - Social control of cell size: males and females are different.
AB  - Successful animals survive because they modify their behavior in response to
      changes in their physical and social environments. Some responses such as fleeing
      or fighting, are immediate and can be understood or at least described by their
      proximate causes. Other modifications occur in animals over a longer time frame
      because they require tissue growth (or loss), changes in responsiveness to
      signalling molecules, or other alterations in the regulation of physiological
      systems. There are numerous examples of the short-term cause-effect relationships
      which are known in some detail. In contrast, less is known about how long-term
      changes result from environmental or social signals. Since reproduction is
      arguably the single most important aspect of an animal's life, reproductive
      behaviors offer a unique chance to study such change. Reproduction requires
      exquisite coordination of physiological state and behavioral acts. Many aspects
      of reproductive behavior occur only under natural conditions so it is imperative
      to analyze naturally occurring behaviors in real animals, preferably in the
      natural habitat. We have been studying an African cichlid fish in natural and
      semi-natural conditions because the connection between physiology and behavior
      can be easily seen. Moreover, the consequence of social success can be traced
      directly to changes in the brain, both in the short and long term. In this
      species, territorial males inhibit sexual maturation of nonterritorial males
      during development. Even after a male becomes sexually mature and territorial,
      being defeated causes his gonads to regress rapidly.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7568873
TI  - Molecular biology of transmissible spongiform encephalopathies.

PMID- 7568876
TI  - Functions of the L2/HNK-1 carbohydrate in the nervous system.

PMID- 7568877
TI  - Neurotrophic factors and their receptors.

PMID- 7568878
TI  - Induction of non-catalytic TrkB neurotrophin receptors during lesion-induced
      synaptic rearrangement in the adult rat hippocampus.

PMID- 7568879
TI  - Plasticity of developing neuromuscular synapses.
AB  - Developing neuromuscular synapses are susceptible to modulation by the presence
      of synaptic activity and a number of chemical factors originated from either pre-
      or postsynaptic cells. In vitro studies of functional modulation of synaptic
      strength by electrical stimulation of pre- and postsynaptic cells suggested an
      essential role of retrograde interactions at developing synapses.

PMID- 7568881
TI  - Molecular genetic analyses of myelin deficiency and cerebellar ataxia.

PMID- 7568882
TI  - Stimulation of phospholipase A2 expression in rat cultured astrocytes by LPS, TNF
      alpha and IL-1 beta.
AB  - Results from this study are in good agreement with those reported by Oka and
      Arita (1991) who demonstrated induction of PLA2 mRNA expression in primary
      astrocytes in response to LPS, TNF alpha and IL-1 beta. In general, the increase
      in PLA2 mRNA correlated well with the extent of PLA2 secretion into the culture
      medium. Using the immortalized astrocyte cell line (DITNC), similar induction of
      PLA2 mRNA expression and secretion of the enzyme into the culture medium could be
      observed. The lack of hydrolysis of labeled PI to DG further confirmed the
      specificity of cytokine induction of PLA2 release into the culture medium. By
      comparing the time course for PLA2 release with that for LDH release, it can be
      concluded that cytokine induction of PLA2 release is not related to events
      accompanying cell death due to serum deprivation. Although it has been well
      demonstrated that exposure of astrocytes to LPS can induce the synthesis and
      release of TNF alpha and IL-1 beta, the mechanism underlying this event has not
      been elucidated (Lieberman et al., 1989). Furthermore, how LPS as well as other
      cytokines induce the mRNA expression and secretion of PLA2 remains to be
      investigated. The availability of the immortalized astrocyte cell line (DITNC)
      will be a useful tool for this type of study. These cells are easy to culture and
      large preparations can be obtained. In addition, these cells will be useful as a
      model to relate the effects of cytokines on other cellular and metabolic events
      that may be directly or indirectly linked to the PLA2 cascade.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7568883
TI  - Correlation between proto-oncogene, fibroblast growth factor and adaptive
      response in brain infarct.
AB  - Ischemia/hypoxia rapidly induce ischemic changes in vulnerable neurons: cortical
      neurons in layers II-III and V, hippocampal neurons, cerebellar Purkinje cells
      and certain basal ganglia and brainstem neurons. The ischemic changes are
      manifested histologically by nuclear pyknosis, cytoplasmic shrinkage and
      basophilia. These neurons exhibit strong and persistent expression of immediate
      early genes (IEGs): c-fos and c-jun. The onset of IEG expression is followed
      within a day by enhanced bFGF expression in non-ischemic neurons in the same
      general regions. The appearance of bFGF is followed within another day by
      proliferation of blood vessels, macrophages and glial cells around the infarct.
      The newly-formed blood vessels and macrophages migrate into the necrotic infarct
      aiming at disposal of the necrotic debris. The gliosis although concentrated
      around the infarct spreads to involve remote regions of both hemispheres. Based
      on the spatiotemporal correlation between cell proliferation and bFGF and the
      known mitogenic properties of bFGF, we believe that this molecule may be
      responsible for the late response in brain infarct including angiogenesis,
      gliosis and macrophage proliferation. The physiological roles of IEGs in the
      chain of adaptive response following brain infarction and its relationship with
      bFGF are subjects pending future investigations.

PMID- 7568880
TI  - A RT-PCR study of gene expression in a mechanical injury model.

PMID- 7568884
TI  - Gene expression in astrocytes during and after ischemia.
AB  - Involvement of the IEGs in brain injury and ischemia is under intensive
      investigation (Gubits et al., 1993). There are several families of the IEGs. They
      include the fos, jun, and zinc finger genes that encode transcription factors.
      Products of the fos family (c-fos, fra-1, fra-2, and fos B) bind to members of
      the jun family (c-jun, jun B, jun D) via leucine zippers, and this dimer then
      binds to the AP-1 site (consensus sequence -TGACTCA-) in the promoter of target
      genes, which in turn regulate the expression of late response genes that produce
      long-term changes in cells. For example, c-fos may regulate the long-term
      expression of preproenkephalin, nerve growth factor, dynorphin, vasoactive
      intestinal polypeptide, tyrosine hydroxylase and other genes with AP-1 sites in
      their promoters (Curran and Morgan, 1987; Sheng and Greenberg, 1990). It is
      likely that the c-fos gene up-regulation observed in ischemic astrocytes leads to
      the changes observed in the expressions of hsp and cytoskeleton protein genes in
      this experimental model. This is supported by the findings of Sarid (1991) and
      Pennypacker et al. (1994) who have shown that AP-1 DNA binding activity in
      hippocampus recognized an AP-1 sequence from the promoter region of the GFAP
      which is a potential target gene. van de Klundert et al. (1992) also suggested
      the involvement of AP-1 in transcriptional regulation of vimentin. IEGs can be
      induced within minutes by extracellular stimuli including transmitters, peptides,
      and growth factors. In this study, we have shown that c-fos induction by ischemia
      was rapid and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7568887
TI  - The transport of neurotransmitters into synaptic vesicles.
AB  - Using selection in the neurotoxin MPP+, we have isolated a cDNA encoding
      vesicular amine transport. The transporter protects against MPP+ by sequestering
      the toxin in vesicles, away from its primary site of action in mitochondria.
      Unexpectedly, two distinct but highly related genes encode vesicular amine
      transport in the adrenal gland and the central nervous system. The sequence of
      both predicts twelve transmembrane domains and weak homology to a class of
      bacterial antibiotic resistance proteins. The two human genes occur on different
      chromosomes. In addition, the two transporters show a number of differences in
      function, including substrate specificity and the interaction with one inhibitor
      and the amphetamines.

PMID- 7568885
TI  - Gene expression of neurotropic retrovirus in the CNS.
AB  - We isolated a neurotropic retrovirus, FrC6-V, from Friend leukemia virus complex
      after the adaptation of the original virus to newborn rat brain followed by the
      long-term infection of rat glioma cell line C6. When rats were infected with FrC6
      V, the virus was isolated mainly from the brain and from the thymus of the
      infected animals regardless of the age of the animals at the time of inoculation.
      Neurological and neuropathological manifestations became apparent, however, only
      when the newborn rats were infected. The lesions in the brain were characterized
      by spongiform degeneration accompanied by the loss of neurons in the
      hypothalamus, cerebral cortex, and cerebellum. There was almost no inflammatory
      cell infiltration. In primary culture of brain, the astrocytes and the neuron
      specific enolase antigen-positive cells were infected with FrC6-V, but the viral
      antigen was not detected in neurofilament antigen-positive neurons. Furthermore,
      our virus inhibited the differentiation of embryonal carcinoma (EC) cell line P19
      into neurons.

PMID- 7568886
TI  - Cholecystokinin octapeptide (CCK-8): a negative feedback control mechanism for
      opioid analgesia.

PMID- 7568888
TI  - Preliminary molecular neurobiology study on the pathogenesis of primary epilepsy.

PMID- 7568889
TI  - Expression of immune-related molecules in a murine genetic demyelinating disease.

PMID- 7568891
TI  - The gene knockout technology for the analysis of learning and memory, and neural
      development.

PMID- 7568890
TI  - Expression of myelin proteolipid protein in oligodendrocytes and transfected
      cells.
AB  - The data presented in this paper show that the appropriate tools are now
      available to study the behavior of PLP and DM20 transcripts engineered with
      either point mutations or deletion of specific domains. Such studies should begin
      to provide new insights into the functions of PLP and DM20 and their role in
      relation to the optimal functioning of the nervous system.

PMID- 7568892
TI  - Glial fibrillary acidic protein mRNA and the development of gliosis in mice with
      chronic relapsing experimental allergic encephalomyelitis.

PMID- 7568894
TI  - The molecular basis of the neuropathies of mouse and human.

PMID- 7568893
TI  - Structure and function of peripheral nerve myelin proteins.
AB  - (1) Two glycoproteins, P0 and PASII, are widely distributed in the peripheral
      myelin, but not in the central myelin of mammals. P0-like protein is expressed in
      both peripheral and central myelins of some lower vertebrates, such as fish and
      tadpoles. A close relationship is suggested between P0 expression and neural
      regenerative activity. (2) PMP22 was reported to show high sequence homology, not
      only to PASII, but also to the growth arrest specific protein. Human PASII/PMP22
      sequence was deduced and the locus of its gene, chromosome 17p12-p11.2, is
      similar to the region linked to Charcot-Marie-Tooth disease type 1A. (3) P0
      expressed on cultured cells mediated strong homophilic cell adhesion and neurite
      outgrowth. Addition of the P0 glycopeptide inhibited cell adhesion markedly,
      indicating that the oligosaccharide with peptide is essential for P0 mediated
      cell adhesion. The active site for neurite outgrowth in P0 appears to be
      different from the adhesion site. (4) We determined the human chromosomal locus
      of the P0 gene, 1q22-q23, which corresponded to the locus of hereditary motor and
      sensory neuropathy, Charcot-Marie-Tooth disease type 1B. Point mutations in the
      extracellular domain of P0 are found in the patient's chromosome. (5) L1 is a
      large multifunctional adhesive glycoprotein of 200 kD. Rat and human L1 sequences
      confirmed a common structure for the mammalian nervous systems. An isoform of L1
      (L1cs), lacking four amino acids, appears to localize in non-neuronal cells such
      as Schwann cells, while the complete L1 is exclusively found in neurons. L1cs in
      Schwann cells may be functionally different from L1 in neurons.

PMID- 7568897
TI  - The involvement of PKC and multifunctional CaM kinase II of the postsynaptic
      neuron in induction and maintenance of long-term potentiation.

PMID- 7568895
TI  - Expression of the neurofibromatosis type 1 (NF1) gene during mouse embryonic
      development.
AB  - The von Recklinghausen neurofibromatosis type 1 (NF1) gene was identified by
      positional cloning and found to be a tumor suppressor gene expressed most
      abundantly in brain. One isoform of NF1 (type 2 NF1) contains an additional 21
      amino acids inserted into a region of the protein involved in the regulation of
      p21-ras. To study the role of the NF1 gene in mammalian development, the
      expression of the NF1 gene and protein product, neurofibromin, during mouse
      embryonic development was determined. NF1 mRNA and neurofibromin expression was
      detectable by Northern and Western analysis, respectively, after day 10 of murine
      embryogenesis and remained elevated throughout development. Type 2 NF1 mRNA
      expression predominated before day 10, after which time, type 1 (lacking the
      insertion) NF1 mRNA was the predominant isoform detected. The protein expression
      of the type 2 isoform was similar to overall neurofibromin expression by Western
      blot analysis with greatest expression in adult brain. Despite a similar tissue
      distribution pattern, type 2 neurofibromin was not found to be associated with
      brain cytoplasmic microtubules in the same fashion as the uninserted type 1
      isoform. Collectively, these experiments suggest that the switch from type 2 to
      type 1 neurofibromin isoform predominance during embryogenesis may have
      significant functional consequences.

PMID- 7568896
TI  - Gene expression of serotonergic neurons in the central nervous system: molecular
      and developmental analysis.

PMID- 7568898
TI  - Neuronal calcium channels encoded by the alpha 1A subunit and their contribution
      to excitatory synaptic transmission in the CNS.

PMID- 7568901
TI  - Decoding Ca2+ signals to the nucleus by multifunctional CaM kinase.
AB  - Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is one of
      the major protein kinases coordinating cellular responses to neurotransmitters
      and hormones. CaM kinase transduces changes in intracellular free Ca2+ into
      changes in the phosphorylation state and activity of target proteins involved in
      neurotransmitter synthesis and release, neuronal plasticity and gene expression.
      Structure/function analyses of the kinase reveal the kinase is kept inactive in
      its basal state by a regulatory domain that is displaced by the binding of
      Ca2+/calmodulin. Once activated by Ca2+/calmodulin, autophosphorylation occurs if
      a pair of proximate subunits of the decameric kinase have calmodulin bound. The
      frequency of Ca2+ oscillations or spikes may be decoded by CaM kinase via this
      autophosphorylation. Calmodulin is essentially trapped by autophosphorylation
      which converts CaM kinase into a high affinity calmodulin-binding protein.
      Repetitive stimulation of the kinase may promote recruitment of calmodulin to the
      kinase so that it becomes increasingly active with each stimulus in a frequency
      dependent manner. The association domain at the C-terminal end of CaM kinase
      contains a variable region that targets isoforms of the kinase to the nucleus or
      cytoskeleton and assembles the kinase into a decameric structure. Alternative
      splicing introduces a short nuclear localization signal that targets transfected
      kinase to the nucleus where it may regulate nuclear functions. The regulatory
      properties of CaM kinase provide for molecular potentiation of Ca2+ signals and
      frequency detection whereas its association domain should enable it to decode
      such Ca2+ fluctuations in the nucleus.

PMID- 7568899
TI  - Synaptic vesicle proteins and regulated exocytosis.
AB  - The recent identification of novel proteins associated with the membranes of
      synaptic vesicles has ignited the field of molecular neurobiology to probe the
      function of these molecules. Evidence is mounting that the vesicle proteins vamp
      (synaptobrevin), rab3A, synaptophysin, synaptotagmin (p65) and SV2 play an
      important role in regulated exocytosis, by regulating neurotransmitter uptake,
      vesicle targeting and fusion with the presynaptic plasma membrane.

PMID- 7568900
TI  - The molecular organization of voltage-dependent K+ channels in vivo.

PMID- 7568902
TI  - The role of nitric oxide and other endothelium-derived vasoactive substances in
      vascular disease.
AB  - Alteration in the release and action of endothelium-derived vasoactive factors is
      responsible for changes in vascular reactivity early in the course of vascular
      disease. These factors include nitric oxide, eicosanoids, endothelium-derived
      hyperpolarizing factor, endothelin, and angiotensin II. Because endothelial
      dysfunction occurs at early stages of disease, it may reflect physiological
      changes that, if allowed to become chronic, are responsible for changes in
      vascular structure and growth and adhesivity to platelets and leukocytes,
      ultimately leading to atherosclerosis and thrombosis. Each of the major risk
      factors predisposing to vascular disease are associated with endothelial cell
      dysfunction, suggesting a direct etiologic link between the effects of the risk
      factors on the endothelium and their propensity to accelerate vascular disease.
      Restoration or replacement of endothelium-derived factors such as nitric oxide
      and prostacyclin, which impede the progression of vascular disease, or preventing
      the action of mediators such as vasoconstrictor eicosanoids, angiotensin II, or
      endothelin, which accelerate the progression of vascular disease, has become a
      useful paradigm in the treatment and prevention of vascular disease. Thus,
      understanding the physiology of endothelium-derived vasoactive factors is a
      necessary part of every physician's education.

PMID- 7568903
TI  - Atherosclerosis, oxidative stress, and antioxidant protection in endothelium
      derived relaxing factor action.
AB  - The vascular endothelium plays a central role in the regulation of vascular
      function. In particular, the local release of endothelium-derived relaxing factor
      (EDRF) regulates vascular tone and prevents platelet adhesion to the vascular
      wall. Impairment of EDRF action develops early in atherosclerosis and, in part,
      contributes to platelet deposition and vasospasm involved in the clinical
      expression of coronary artery disease. Recent evidence suggests that an imbalance
      between vascular oxidative stress and antioxidant protection is involved in the
      development of this vascular dysfunction. In this report, the relation between
      oxidative stress, atherosclerosis, and abnormal EDRF action is reviewed with
      particular attention to the effects of antioxidant supplementation in animal
      models of atherosclerosis and hypercholesterolemia.

PMID- 7568904
TI  - Role of nitric oxide in the regulation of myocardial function.
AB  - Nitric oxide (NO), produced by either constitutive or inducible isoforms of NO
      synthase (cNOS or iNOS), influences myocardial inotropic and chronotropic
      responses. This pathway has been studied using NO donors or NOS inhibitors or by
      immune-mediated stimulation of iNOS. Although inhibition of constitutive NO
      activity in the heart does not influence indices of myocardial contractility, NO
      donors, in some species and preparations, may exert a negative inotropic effect
      as well as an enhancement of diastolic relaxation. The best documented cardiac
      action of NO is inhibition of the positive inotropic and chronotropic responses
      to beta-adrenergic receptor stimulation. Basal NO production, presumable via
      cNOS, appears to exert a mild tonic inhibition of beta-adrenergic responses. On
      the other hand, excessive NO production mediated by iNOS may contribute to the
      myocardial depression and beta-adrenergic hyporesponsiveness associated with
      conditions such as sepsis, myocarditis, cardiac transplant rejection, and dilated
      cardiomyopathy. Muscarinic cholinergic stimulation of the heart appears to
      stimulate NO production that mediates, at least partially, parasympathetic
      slowing of heart rate and inhibition of beta-adrenergic contractility. NO
      stimulated production of 3',5'-cyclic guanosine monophosphate via guanylyl
      cyclase accounts for many of the observed physiological actions of NO. 3',5'
      Cyclic guanosine monophosphate inhibits the beta-adrenergic-stimulated increase
      in the slow-inward calcium current and reduces the calcium affinity of the
      contractile apparatus, actions that could contribute to a negative inotropic
      effect, an abbreviation of contraction, and an enhancement of diastolic
      relaxation. Biochemical, immunocytochemical, and molecular biological techniques
      have been used to show the presence of both cNOS and iNOS within the myocardium.
      cNOS is expressed in myocytes, endothelial cells, and neurons in the myocardium,
      and there is evidence for iNOS in myocytes, small vessel endothelium, vascular
      smooth muscle cells, and immune cells that infiltrate the heart. Taken together,
      these observations suggest that NO influences normal cardiac physiology and may
      play an important role in the pathophysiology of certain disease states
      associated with cardiac dysfunction.

PMID- 7568907
TI  - Novel functions of cholinesterases in development, physiology and disease.

PMID- 7568906
TI  - Nitric oxide and its role in the cardiovascular system.
AB  - Nitric oxide (NO) is a ubiquitous, naturally occurring molecule found in a
      variety of cell types and organ systems. In the cardiovascular system, NO is an
      important determinant of basal vascular tone, prevents platelet activation,
      limits leukocyte adhesion to the endothelium, and regulates myocardial
      contractility. NO may also play a role in the pathogenesis of common
      cardiovascular disorders, including hypotension accompanying shock states,
      essential hypertension, and atherosclerosis. In this review, we discuss the
      biochemistry of NO and focus on its biology and pathophysiology in the
      cardiovascular system.

PMID- 7568905
TI  - Electrophysiologic and proarrhythmic effects of intravenous inotropic agents.
AB  - Intravenous inotropic agents promote increased myocardial contractility via
      elevation of myocyte calcium concentrations, a mechanism that is also known to
      promote the development of cardiac arrhythmias. The purpose of this article is to
      review the electrophysiologic effects and relative potential for proarrhythmia
      associated with dobutamine, dopamine, and the phosphodiesterase inhibitors
      amrinone and milrinone. Dobutamine increases sinoatrial node automaticity and
      decreases atrial and atrioventricular (AV) node refractoriness and AV nodal
      conduction time. The drug also decreases ventricular refractoriness in both
      healthy and ischemic myocardium. Dobutamine has been shown to increase heart rate
      in a dose-related fashion in animals and in humans. In humans, dobutamine has
      been reported to induce ventricular ectopic activity (VEA) in 3% to 15% of
      patients, although VEAs are often asymptomatic, requiring no intervention.
      Ventricular tachycardia (VT) associated with dobutamine appears to occur rarely.
      Patients with underlying arrhythmias or heart failure or those receiving
      excessive doses of dobutamine are at greatest risk for proarrhythmia. Dopamine
      increases automaticity in Purkinje fibers and has a biphasic effect on action
      potential duration. Dopamine has been reported to induce atrial or ventricular
      arrhythmias in animals. In humans, dopamine may be associated with dose-related
      sinus tachycardia but has also been reported to cause VEA, which is usually
      asymptomatic. Dopamine-associated VT appears to occur rarely. Dopamine produces
      greater elevations in heart rate or frequency of ventricular premature beats at a
      given value of cardiac index than does dobutamine. The phosphodiesterase
      inhibitors amrinone and milrinone increase conduction through the AV node and
      decrease atrial refractoriness. Intravenous administration of these drugs may
      result in sinus tachycardia in some patients and has been reported to cause VEA,
      which is often asymptomatic, in up to 17% of patients. VT has also been reported
      in association with short-term use of intravenous phosphodiesterase inhibitors.
      In summary, intravenous inotropic agents may be associated with proarrhythmic
      effects in some patients. The primary arrhythmias reported are sinus tachycardia
      and VEA, although other supraventricular or ventricular arrhythmias have been
      reported less commonly. However, clinically significant proarrhythmic effects
      associated with these agents appear to occur rarely, and, at conventional doses,
      intravenous inotropic agents are relatively safe with respect to proarrhythmic
      effects.

PMID- 7568908
TI  - The isolated mammalian spinal cord.
AB  - This review considers: spinal cord slices; isolated spinal cord sagitally or
      transversely hemisected; whole spinal cord; respiration control--[brain-stem
      spinal cord; brain-stem spinal cord with attached lungs]; nociception--[spinal
      cord with tail]; fictive locomotion--[spinal cord with one hind limb; spinal cord
      with two hind limbs]. Much of the functional circuitry of the CNS can be studied
      in the isolated spinal cord with the additional advantage that the isolated
      spinal cord can be perfused with known concentrations of ions, neurotransmitters,
      agonists, antagonists, and anaesthetics. These can be washed away, the circuitry
      allowed to recover and other drugs or different concentrations applied. Future
      preparations including the complete spinal cord, the two hind limbs, and a
      sagittal section of the complete brain will allow greater understanding of the
      multiple sensory and motor pathways and their interactions in the CNS.

PMID- 7568909
TI  - Secretogranin II: molecular properties, regulation of biosynthesis and processing
      to the neuropeptide secretoneurin.
AB  - Secretogranin II is an acidic secretory protein in large dense core vesicles of
      endocrine, neuroendocrine and neuronal tissues. It comprises, together with
      chromogranins A and B, the class of proteins collectively called chromogranins.
      In this review the physico-chemical properties, genomic organization, tissue
      distribution, synthesis regulation, ontogeny and physiological function of this
      protein are discussed. Secretogranin II gained interest recently for mainly three
      reasons: (1) secretogranin II is an excellent marker for the regulated secretory
      pathway due to its simple and specific metabolic labeling by inorganic sulfate;
      (2) secretogranin II occurs in a variety of neoplasms arising from endocrine and
      neuroendocrine cells and was shown to be a useful histological tumor marker for
      these cells; (3) secretogranin II is the precursor of the recently discovered
      neuropeptide secretoneurin which induces dopamine release in the striatum of the
      rat brain.

PMID- 7568910
TI  - The S-100: a protein family in search of a function.
AB  - The S-100 is a group of low molecular weight (10-12 kD) calcium-binding proteins
      highly conserved among vertebrates. It is present in different tissues as dimers
      of homologous or different subunits (alpha, beta). In the nervous system, the S
      100 exists as a mixture composed of beta beta and alpha beta dimers with the
      monomer beta represented more often. Its intracellular localisation is mainly
      restricted to the glial cytoplasmic compartment with a small fraction bound to
      membranes. In this compartment the S-100 acts as a potent inhibitor of
      phosphorylation on several substrates including the synaptosomal C-Kinase and
      Tau, a microtubule-associated protein. The S-100 in particular conditions, after
      binding with specific membrane sites (Kd = 0.2 microM; Bmax = 4.5 nM), is able to
      modify the activity of adenylate cyclase, probably via G-proteins. In addition,
      the Ca2+ homeostasis is also modulated by S-100 via an increase of specific
      membrane conductance and/or Ca2+ release from intracellular stores. "In vitro"
      and "in vivo" experiments showed that lower (nM) concentrations of extracellular
      S-100 beta act on glial and neuronal cells as a growth-differentiating factor. On
      the other hand, higher concentrations of the protein induce apoptosis of some
      cells such as the sympathetic-like PC12 line. Finally, data obtained from
      physiological (development, ageing) or pathological (dementia associated with
      Down's syndrome, Alzheimer's disease) conditions showed that a relationship could
      be established between the S-100 levels and some aspects of the statii.

PMID- 7568911
TI  - Molecular aspects of tetanus and botulinum neurotoxin poisoning.
AB  - Clostridial neurotoxins, tetanus and the botulinum toxins A-G, are high molecular
      weight proteins consisting of a heavy chain which is responsible for the
      internalisation and a light chain possessing a zinc-dependent proteolytic
      activity. They exclusively proteolyse either the vesicle membrane protein,
      synaptobrevin or two integral plasma membrane proteins, SNAP 25 and syntaxin.
      Together with cytosolic proteins these proteins form the SNARE complex involved
      in vesicle exocytosis, and their cleavage blocks the latter process. Clostridial
      neurotoxins have now become powerful tools to investigate the final events
      occurring during secretion in neuronal, endocrine, and non-neuronal cells. They
      are applied to dissect the specific interactions of the SNARE protein complex
      with cytosolic fusogens and other modulators of exocytosis. Whereas exocytosis is
      not essential for the survival of cells, the organism as a whole will fall victim
      to a few nanograms since interneuronal and neuromuscular transmission is vital to
      muscular control, especially in respiration. Although all clostridial neurotoxins
      by their light chains attack proteins of the SNARE complex, tetanus toxin and the
      various botulinum toxins differ dramatically in their clinical symptoms. The
      biological information for this difference resides on the respective heavy chains
      which select different transport routes carrying the light chain from the place
      of entrance to the final compartment of action. So far the different transport
      vesicles used either by the various botulinum neurotoxins or by tetanus toxin are
      not yet defined. Nevertheless at least one of the botulinum toxins serves as a
      beneficial drug in the treatment of severe neuromuscular spasms.

PMID- 7568912
TI  - Chemical anatomy of primate basal ganglia.
AB  - This paper provides an overview of the anatomical and functional organization of
      the most prominent chemospecific neuronal systems that compose the basal ganglia
      in primates. Emphasis is placed on the heterogeneity and diversity of small
      molecule transmitters, neuroactive peptides and proteins used by basal ganglia
      neurons. Dopaminergic, serotoninergic and cholinergic neuronal systems are shown
      to comprise multiple subsystems organized according to highly specific patterns.
      These subsystems differentially regulate gene expression of several neuroactive
      peptides, including tachykinins, enkephalins, dynorphin, somatostatin, and
      neuropeptide Y, that are used by distinct subsets of basal ganglia neurons.
      Glutamatergic excitatory inputs establish distinct functional territories within
      the basal ganglia, and neurons in each of these territories act upon other brain
      neuronal systems through a GABAergic disinhibitory output mechanism. A striking
      complementary pattern of distribution of the calcium-binding proteins parvalbumin
      and calbindin D-28k is noted in all basal ganglia components. The limbic system
      associated membrane protein (LAMP) is confined chiefly to basal ganglia sectors
      that are anatomically and functionally related to limbic system structures; these
      may serve as functional interfaces between the basal ganglia and the limbic
      system. The functional status of the various basal ganglia chemospecific systems
      in neurodegenerative diseases, such as Parkinson's disease and Huntington's
      chorea, is examined. It is concluded that these multiple transmitter-related
      systems cannot be analyzed separately as they form highly complex and interactive
      neuronal networks. These complexities should be taken into account to reach a
      better understanding of the functions of primate basal ganglia in health and
      disease.

PMID- 7568913
TI  - The role of the cerebello-thalamo-cortical pathway in skilled movement.
AB  - Studies of lesions of the primate cerebellum leave little doubt that the
      cerebellum is necessary for the execution of smooth and accurate movements. How
      the cerebellum fulfills this role at a neuronal level remains unknown. It is
      likely that the cerebellum exerts the same effect on a number of different
      efferent targets. In order to influence voluntary movement, a major output from
      the cerebellum projects to the motor cortex via the cerebello-thalamo-cortical
      (CTC) pathway. By examining neuronal activity in the cerebellar thalamus, and
      comparing this with activity recorded from its connections with the deep
      cerebellar nuclei and motor cortex, conclusions can be made regarding cerebellar
      function. Current data does not support a role for the CTC pathway in the
      initiation of movement or the control of trans-cortical reflexes. Also, the
      evidence does not support the hypothesis that the cerebellum prevents terminal
      movement oscillations by predictively sending a message to the antagonist muscle
      to brake the movement. The available literature supports the Eccles theory that
      during normal movement, the CTC pathway receives a form of efference copy from
      the motor cortex and compares this message with that derived from peripheral
      afferents about the actual progress of the movement. However, there is not a
      significant degree of kinematic information passing through this pathway in the
      course of a voluntary movement. Therefore the actual site of comparison or error
      detection in this system awaits further elucidation.

PMID- 7568914
TI  - Urine storage mechanisms.
AB  - The urine storage process depends upon the coordinated control of a storage
      chamber, the bladder body, and its outlets, the bladder base and urethra. While
      urine storage disorders are of considerable clinical significance, the mechanisms
      underlying this process are poorly understood. Many species possess an ability to
      alter the duration of urine storage in the face of widely varying filling rates.
      The storage chamber appears largely responsible for this ability to alter
      capacity and compliance. However, there has been some controversy over the
      contribution of intrinsic smooth muscle and extrinsic neural systems to the
      storage process, which is partly related to the various methodologies used in
      experimental and clinical studies. Thus, the storage phase is greatly influenced
      by the filling regimes, anaesthesia, non-specific factors and infusates used in
      these studies. Further, the techniques used to examine and measure urine storage
      mechanisms often obscure the subtle nature of this process. There is little doubt
      that, under natural filling conditions, myogenic factors allow the bladder to
      store increasing volumes at low pressure. More recent studies indicate that, in
      addition to a quiescent parasympatho-excitatory drive, the extrinsic neural
      systems contribute to the storage phase with a precisely controlled sympatho
      inhibitory drive. However, the sympatho-inhibitory drive does not increase
      capacity by promoting high compliance. Instead this drive partially reduces the
      level of bladder wall tension transduced by the bladder wall mechanoreceptors,
      and thus delays the time at which the micturition tension threshold is reached.

PMID- 7568916
TI  - Neural regeneration in gastropod molluscs.
AB  - Snails recover function following a variety of neural injuries. They grow new
      tentacles with associated tentacle ganglia, selectively reinnervate peripheral
      targets, repair central connections and may even replace lost neurons and
      ganglia. The plasticity revealed in their responses to neural injury is an
      extreme expression of the adaptability observed in studies of learning and age
      related changes in the nervous system. Recent information on neurogenesis in
      gastropods is providing a basis for comparing developmental events with neural
      regeneration. Studies of neural regeneration in gastropods have capitalized on
      our ability to identify many gastropod neurons individually and characterize the
      cellular properties and network properties that generate output patterns that
      underlie behaviors. The robustness of the model systems formed by cultured
      gastropod neurons is apparent in the similarity of the activity patterns in
      circuits formed in vitro and in vivo. Cell membrane repair, activation of an
      altered pattern of protein synthesis, and observation of the searching action of
      the growth cones can be studied under defined conditions that promote or inhibit
      the processes. Basic properties of growth cones, the molecular binding and second
      messenger systems underlying adhesion, sprouting and pathfinding, and events in
      synaptogenesis are accessible to analysis. Rules that govern selection of
      synaptic partners are being evaluated on the basis of cellular characteristics
      such as transmitter and receptor expression and ganglion of origin. The
      conservation of the molecular language that governs growth and communication
      between cells suggest that information gained in such studies may some day be
      applied to promote neural regeneration in mammals.

PMID- 7568915
TI  - Molecular mechanisms of gustatory transduction in frog taste cells.
AB  - In this review, we focussed on gustatory transduction mechanisms in frog taste
      cells on the basis of our research data. The frog taste cells were stimulated
      with four basic taste stimuli and pure water, and the receptor potentials and
      currents were recorded with microelectrode and patch pipette techniques. The
      taste cell membrane is divided into the apical receptive and basolateral
      membranes. It is concluded that receptor potentials in frog taste cells evoked by
      salt, acid, bitter, sugar and water stimuli are generated by currents through
      various types of ionic channels and pumps in the apical receptive and basolateral
      membranes.

PMID- 7568917
TI  - 'Vestibular compensation': neural plasticity and its relations to functional
      recovery after labyrinthine lesions in frogs and other vertebrates.
AB  - Removal of the labyrinthine organs on one side is followed by a number of severe
      postural and dynamic reflex deficits. Some of these deficits, in particular the
      posture of head and body, are normalized again over a period that varies strongly
      between species. Other, more persistent motor deficits are substituted, e.g. by
      the saccadic system. This partial normalization of the function is accompanied by
      changes in response properties of the central vestibular neurons on the operated
      side. Available evidence suggests the occurrence of reactive synaptogenesis in
      cat and frog. In the latter species the synaptic efficacy of commissural
      vestibular connections increases and the metabolic activity of central vestibular
      neurons on the operated side recovers post-operatively. The onset of both
      changes, however, is delayed by about 30 days, which is too late to be causally
      related with the initial, rapid period of postural recovery in frog and cat. In
      frogs additional, early (7-15 days p.o.) and late (45-60 p.o.) synaptic changes
      were detected in the branchial spinal cord. These multiple changes survive the
      isolation of the spinal cord and must be propriospinal in origin. Selective
      lesions of individual vestibular nerve branches indicate that inactivation of
      utricular inputs is a sufficient and necessary condition to provoke postural
      deficits and early spinal changes similar to those after hemilabyrinthectomy.
      Therefore, a close correlation between spinal plasticity and postural recovery is
      indicated. In essence, the elimination of vestibular afferent inputs results in a
      series of behavioral distortions that are partially normalized by a multitude of
      synaptic mechanisms at distributed anatomical sites over different periods of
      time.

PMID- 7568919
TI  - [Oxidative reactions of the base moiety in purine nucleosides and their
      applications].

PMID- 7568918
TI  - [Advance in synthesis of sugar-modified nucleosides].

PMID- 7568920
TI  - [Synthesis of novel nucleosides: carbocyclic nucleosides].

PMID- 7568922
TI  - [Nucleoside analogues as anti-herpes agents and their mode of action].

PMID- 7568923
TI  - [Nucleosides and related compounds which act as inhibitors against replication of
      HIV-1].

PMID- 7568921
TI  - [Design of antitumor 2'-deoxy-(2'-C-substituted) cytidines].

PMID- 7568925
TI  - [Phosphodiesterase inhibitor: griseolic acid, its' derivatives and their
      biological activities].

PMID- 7568924
TI  - [Design of S-adenosylhomocystein hydrolase (SHAase) inhibitors as potent anti-RNA
      viral agents].

PMID- 7568926
TI  - [Recent adenosine antagonists].

PMID- 7568927
TI  - [Mechanism of anti-leishmanial drugs on the basis of the nucleoside structures].

PMID- 7568928
TI  - [Inhibitors of inosine monophosphate dehydrogenase and their biological
      activities].

PMID- 7568931
TI  - [The chemistry of phosphorus: pseudorotation].

PMID- 7568930
TI  - [Synthesis and properties of 2'-phosphorylated oligoribonucleotides].

PMID- 7568932
TI  - [New and large scale syntheses of nucleoside polyphosphates].

PMID- 7568929
TI  - [Synthesis of oligodeoxyribonucleotides with modified internucleotide phosphate
      residues].

PMID- 7568933
TI  - [Chemical synthesis of nucleopeptide].

PMID- 7568935
TI  - [Molecular design of oligonucleotide porphyrin derivatives].

PMID- 7568934
TI  - [Synthesis and properties of Oligonucleotides with modified sugar fragment].

PMID- 7568936
TI  - [Molecular design of antisense oligonucleotide].

PMID- 7568937
TI  - [Labeling for the studies on dynamic properties of antisense molecules].

PMID- 7568938
TI  - [Regulation of gene expression by antisense molecule].

PMID- 7568939
TI  - [Recent developments in the field of antigene oligonucleotides].

PMID- 7568940
TI  - [Synthesis of oligonucleotide analogues by the post-elongation modification
      methods].

PMID- 7568941
TI  - [Structure and molecular design of ribozymes].

PMID- 7568942
TI  - [Structures and functions of small nuclear RNAs involved in pre-mRNA splicing].

PMID- 7568943
TI  - [Inhibition of HIV replication by ribozyme strategy].

PMID- 7568944
TI  - [RNA ligands for HIV proteins].

PMID- 7568945
TI  - [Molecular design of artificial nucleases].

PMID- 7568946
TI  - [Mechanism of oxidative DNA strand scission].

PMID- 7568947
TI  - [Design of a novel Zn finger-based DNA cutter].

PMID- 7568949
TI  - [tRNA identify--a view of Escherichia coli system].

PMID- 7568948
TI  - [Modified nucleosides of tRNA in decoding].

PMID- 7568950
TI  - [Structure and function of ribosomal RNA].

PMID- 7568951
TI  - [Structural analysis of ribozymes].

PMID- 7568952
TI  - [Stable isotopic labeling and NMR analyses of nucleic acids].

PMID- 7568953
TI  - [Preparation of stable isotope labeled DNA oligomers: applications to the
      structural analysis of nucleic acids by heteronuclear multidimensional NMR
      spectroscopy].

PMID- 7568954
TI  - [The noncanonical base pairings in crystal structure].

PMID- 7568957
TI  - [Stability prediction of active structures of nucleic acids].

PMID- 7568956
TI  - [Structural analysis of nucleic acids by the use of Raman microscope].

PMID- 7568958
TI  - [Dynamics of the high order structure of giant DNA--single molecular observation
      by fluorescence microscopy].

PMID- 7568955
TI  - [Structural motifs in interactions of nucleic acids].

PMID- 7568961
TI  - [Structure of four-stranded telomeric DNA].

PMID- 7568959
TI  - [Mechanisms of nucleoside-analog mutagenesis].

PMID- 7568960
TI  - [DNA lesions produced by active oxygen and their induced mutations].

PMID- 7568962
TI  - [Unusual single-stranded DNA structures: extraordinarily thermo-stable mini
      hairpin].

PMID- 7568963
TI  - [Specific DNA recognition by Myb protein].

PMID- 7568964
TI  - [Structure determination of transcription factors].

PMID- 7568965
TI  - [Mechanism of tRNA-recognition by aminoacyl-tRNA synthetases].

PMID- 7568966
TI  - [Structure and function of the Ada protein].

PMID- 7568968
TI  - [Three-dimensional structure and reaction mechanism of ribonuclease A].

PMID- 7568967
TI  - [RNase T1-nucleotide interaction].

PMID- 7568969
TI  - [Mechanisms of the recognition of homologous DNA molecules by RecA protein].

PMID- 7568970
TI  - [Nucleic acid chemistry in Japan: past, present, and future].

PMID- 7568971
TI  - [Nucleic acid chemistry and protein engineering].

PMID- 7568972
TI  - [Recall of our tRNA research for last 30 years].

PMID- 7568973
TI  - [Numerous unforgettable moments in our research on nucleic acids].

PMID- 7568975
TI  - [From simplicity base for oligonucleotide].

PMID- 7568974
TI  - [Achievement of Dr. H. G. Khorana and nucleic acids chemistry].

PMID- 7568976
TI  - [Hold high up the torch of nucleic-acid chemistry].

PMID- 7568977
TI  - Hepatitis A vaccine.

PMID- 7568978
TI  - Management prerogative.

PMID- 7568979
TI  - Where have all the nurses gone? Troubling trends in the nursing workforce.

PMID- 7568980
TI  - Enterprise bargaining in private hospitals.

PMID- 7568981
TI  - Where to work?

PMID- 7568982
TI  - Quality care--nurses make the difference.

PMID- 7568984
TI  - [Receptor activity of T lymphocytes in patients with atopic dermatitis].
AB  - The peripheral blood lymphocytes and their activity in ability to form non-immune
      E rosettes before and after treatment were examined in 48 patients with atopic
      dermatitis. Decrease number of peripheral blood T lymphocytes in patients was
      observed. The number of T lymphocytes rosette-forming cells before treatment was
      also diminished. After three months routine treatment the correct value of
      lymphocytes receptors activity was found.

PMID- 7568983
TI  - [The influence of opioid receptor blockade on the behavior of selected
      biochemical and hormonal parameters in patients with renovascular hypertension
      studied under water immersion conditions].
AB  - 10 patients with renovascular hypertension (HRV) and 12 healthy persons were
      examined under water immersion (WI) conditions without and after blockade of
      opioid receptors with 2 mg of naloxone. Blood pressure, body mass, change of
      plasma volume, plasma molality, PRA, and serum values of AVP, aldosterone and
      catecholamines were evaluated. There were no significant changes between the two
      examined groups before and after WI. It seems that the drop in blood pressure
      induced by WI is not only the result of diminished activation of RAAS. The role
      of opioid receptors in controlling blood pressure and other evaluated parameters
      is likely in both examined groups.

PMID- 7568986
TI  - [Examination of the significance of psychological factors in the etiology of
      alopecia areata. I. Examining Type A behavior].
AB  - We tested the significance of psychic factors in the etiology of alopecia areata
      by means of the assessment of the Behaviour Pattern A (BPA)--a particular way of
      regulation of the relations between the individual and the environment, the basis
      of which is a great need for achievement in the individual who realizes this need
      by means of domination and aggressiveness. The testing was carried out by means
      of the Polish Questionnaire for the Assessment of the Behaviour Pattern A in
      adults. 60 patients were tested (31 women and 29 men). The results were compared
      with the normative groups described by Wrzesniewski. The frequency of the
      occurrence of the Behaviour Pattern A in the tested patients may indicate the
      connection of this type of regulation of relations between the individual and the
      environment with the susceptibility to this disease.

PMID- 7568985
TI  - [The response to the hepatitis B virus vaccine in patients undergoing
      hemodialysis and peritoneal dialysis--personal experience].
AB  - In 55 hemodialyzed and 15 patients on CAPD the presence of hepatitis B and C
      markers was estimated before the beginning of the vaccination series against
      hepatitis B with Engerix B vaccine. The initial anti-H Bs antibody titres was
      also estimated in these patients. The patients without H Bs Ag who have the anti
      Hbs titres below 10 IU/I were qualified for this vaccination. The vaccination was
      needed by 40% of hemodialyzed patients H Bs(-) and 93% patients on CAPD. After
      completing the half year lasting series of vaccinations, the serological answer
      in vaccinated patients was estimated. The protective antibody titres above 10
      IU/I was produced by 62.5% of patients on hemodialysis and 64.4% of patients on
      CAPD. The presence of anti-HCV antibodies had insignificant influence on the
      ability of producing the protective antibody titres in vaccinated patients.

PMID- 7568987
TI  - [Concentration of thromboxane B2 in bronchoalveolar lavage fluid in selected
      interstitial pulmonary diseases].
AB  - Thromboxane B2 (TxB2) is believed to play some role in pathogenesis of
      interstitial pulmonary diseases. The concentration of TxB2 in BALF was assayed in
      75 ill and 6 healthy persons. The ill were divided into 6 groups: with active
      sarcoidosis [18], with active sarcoidosis treated with corticosteroids [8], with
      advanced pulmonary fibrosis [15], with moderate pulmonary fibrosis [6], with
      avian fanciers lung after exposition of antigen [16], avian fanciers lung without
      exposition of antigen [13]. Radioimmunological method with the Amersham set to
      assay the concentration of TxB, was used. A rise of TxB2 concentration was
      detected in the group with advanced pulmonary fibrosis. The rise was significant
      compared with the group of healthy persons, those with sarcoidosis, and with
      moderate pulmonary fibrosis. A tendency to higher concentration of TxB2 in
      patients with avian fanciers lung exposed to the allergen was also observed. The
      results indicate that TxB2 takes part in pathogenesis of these interstitial
      pulmonary diseases in which increased number of neutrophils in BALF is found.

PMID- 7568988
TI  - [Autoantibodies against neutrophil cytoplasm and their significance in the
      classification of systemic vasculitis].
AB  - In this article new informations about systemic vasculitis were reviewed.
      Evaluation of ANCA and their antigen specificity is of a great help in
      classification of systemic vasculitis. Among idiopathic systemic vasculitis anti
      serine proteinase antibodies are found in Wegener granuloma, anti-MPO antibodies
      in Churg-Strauss syndrome and in polyarteritis nodosa. Antibodies against other
      components of PMNL granules still remain unknown. The main purpose of this review
      was to underline incidence of systemic vasculitis and the meaning of ANCA in the
      diagnosis and classification of these diseases.

PMID- 7568989
TI  - [The physiological and pathologic role of human gastric lipase].

PMID- 7568990
TI  - [Achalasia--an uncommon cause of severe esophageal motor disorder in children. A
      case history].
AB  - Two girls, a 11- and 15-year-old are presented with a history of recurrent
      episodes of vomiting, failure to gain satisfactory weight and dysphagia secondary
      to an idiopathic achalasia of the esophagus. Attention is drawn to the functional
      pathology, symptoms, diagnostic procedures and several treatment options.

PMID- 7568992
TI  - Contrasting effects of letter-spacing in alexia: further evidence that different
      strategies generate word length effects in reading.
AB  - The reading behaviour of two alexic patients (SA and WH) is reported. Both
      patients are severely impaired at reading single words, and both show abnormally
      strong effects of word length when reading. These two symptoms are characteristic
      of letter-by-letter reading. Experiment 1 examined the pattern of errors when the
      patients read large and small words. Further experiments examined the effects of
      inter-letter spacing on word naming (Experiments 2a and 2b) and the
      identification of letters in letter strings (Experiment 3). For both patients,
      letter identification was better for widely spaced letters in letter strings, and
      this effect was most pronounced for the central letters in the strings. This is
      consistent with abnormally strong flanker interference in letter identification.
      However, inter-letter spacing affected word reading behaviour in the two patients
      in different ways. SA's word reading improved with widely spaced letters; WH's
      word reading was disrupted. This suggests that these patients adopted different
      strategies when reading words. We conclude that several reading behaviours can
      elicit word length effects, and that these different behaviours can reflect
      strategic adaptation to a common functional deficit in patients. We discuss the
      implications both for understanding alexia and for models of normal word
      identification.

PMID- 7568991
TI  - Consequences of a motor programming deficit for rehearsal and written sentence
      comprehension.
AB  - The role of central motor processes in rehearsal was investigated by studying a
      brain-damaged patient with a severe articulatory impairment. Evidence is
      presented that his articulatory impairment is due to a disruption of motor
      programming rather than to peripheral muscle weakness. Despite his motor
      programming deficit, the patient showed normal auditory span and evidence of
      rehearsal for auditorily presented sequences of words. For visual presentation,
      span was reduced and there was no evidence of rehearsal. Also, the patient showed
      excellent sentence comprehension for syntactically complex sentences for both
      auditory and visual presentation. The results imply that central motor processes
      are not critical for normal short-term memory, at least for auditory
      presentation, and that reading comprehension does not depend on inner rehearsal.

PMID- 7568994
TI  - Bias in conditional inference: implications for mental models and mental logic.
AB  - Three experiments are reported in which subjects are given the opportunity to
      make any of the four inferences associated with conditional statements: modus
      ponens (MP), denial of the antecedent (DA), affirmation of the consequent (AC),
      and modus tollens (MT). The primary purpose of the research was to establish the
      generality and robustness of polarity biases that may be occasioned by systematic
      rotation of negative components in the conditional rules. In Experiments 1 & 2,
      three forms of conditionals were used: "if (not) p then (not) q", "(not) p only
      if (not) q" and "(not) q if (not) p". Experiment 1 used a conclusion evaluation
      task, whereas Experiment 2 used a conclusion production task. In Experiment 3,
      thematic conditionals were presented with and without a preceding scenario. The
      biases investigated were (a) affirmative premise bias--the tendency to draw more
      inferences with negative conclusions. The suggestive evidence for affirmative
      premise bias in the literature was not supported: very little evidence was found
      for it in the current experiments. Robust findings of negative conclusion bias
      were, however, found across the three experiments, although the bias was mostly
      restricted to DA and MT inferences. This suggests that the bias is best regarded
      as a difficulty with double negation. The results are discussed with respect to
      both the mental logic and mental model accounts of propositional reasoning.
      Neither theory as currently formulated can explain all of our findings, although
      a plausible revision of each is considered.

PMID- 7568993
TI  - Pupil dilation as a measure of processing load in simultaneous interpretation and
      other language tasks.
AB  - The present study tested whether the pupillary response can be applied to study
      the variation in processing load during simultaneous interpretation. In
      Experiment 1, the global processing load in simultaneous interpretation as
      reflected in the average pupil size was compared to that in two other language
      tasks, listening to and repeating back an auditorily presented text. Experiment 1
      showed clear differences between the experimental tasks. In Experiment 2, the
      task effect was replicated using single words as stimuli. Experiment 2 showed
      that momentary variations in processing load during a lexical translation task
      are reflected in pupil size. Words that were chosen to be more difficult to
      translate induced higher levels of pupil dilation than did easily translatable
      words. Moreover, repeating back words in a non-native language was accompanied by
      increased pupil dilations, in comparison to repetition in the subject's native
      language. In sum, the study lends good support to the use of the pupillary
      response as an indicator of processing load.

PMID- 7568995
TI  - Testing the mental model theory of propositional reasoning.
AB  - Johnson-Laird, Byrne, and Schaeken (1992) present a theory of propositional
      reasoning by mental models. The present study provides a comprehensive test of
      the predictions of that theory for the difficulty of simple disjunctive and
      conditional inferences. The results are largely consistent with the complex
      pattern of predictions. They are discussed in the light of recently proposed
      modifications of the original theory.

PMID- 7568996
TI  - Priming the identification of environmental sounds.
AB  - Three experiments were conducted using a repetition priming paradigm: Auditory
      word or environmental sound stimuli were identified by subjects in a pre-test
      phase, which was followed by a perceptual identification task using either sounds
      or words in the test phase. Identification of an environmental sound was
      facilitated by prior presentation of the same sound, but not by prior
      presentation of a spoken label (Experiments 1 and 2). Similarly, spoken word
      identification was facilitated by previous presentation of the same word, but not
      when the word had been used to label an environmental sound (Experiment 1). A
      degree of abstraction was demonstrated in Experiment 3, which revealed a
      facilitation effect between similar sounds produced by the same type of source.
      These results are discussed in terms of the Transfer Appropriate Processing,
      activation, and systems approaches.

PMID- 7568997
TI  - Implicit learning and concept learning.
AB  - In Experiments 1 and 2, subjects were exposed to letter strings that followed a
      pattern--the second letter was always the same. This exposure was disguised as a
      test of immediate memory. Following this training, subjects could discriminate
      new letter strings following the pattern from letter strings not following the
      pattern more often than would be expected by chance, which is the traditional
      evidence for concept learning. Discrimination was also better than would be
      predicted from subjects' explicit report of the pattern, demonstrating the co
      occurrence of concept learning and implicit learning. In Experiment 3, rules were
      learned explicitly. Discrimination was worse than would be predicted from
      subjects' explicit report, validating the implicit learning paradigm. In
      Experiment 4, deviations from a prototypical pattern were presented during
      training. In the test of discrimination, prototypes were as familiar as old
      deviations and more familiar than new deviations, even when considering only
      implicit knowledge. Experiment 5 found implicit knowledge of a familiar concept.
      These results are consistent with the hypothesis that the distinguishing features
      of a concept can be learned implicitly, and that one type of implicit learning is
      concept learning.

PMID- 7568998
TI  - Instrumental outcome devaluation is attenuated by the anti-emetic ondansetron.
AB  - In three experiments we assessed the effect of an anti-emetic, the selective 5-HT
      antagonist ondansetron, on (1) the conditioning of a taste aversion using lithium
      chloride (LiCl); (2) the expression of that aversion; and (3) instrumental
      outcome-devaluation effects. In Experiment 1 it was found that ondansetron
      reduced the aversion induced by LiCl when administered prior to the LiCl
      injection and also attenuated the expression of that aversion when administered
      prior to test sessions. In Experiments 2 and 3, thirsty rats were trained, in a
      single session, to lever press and chain pull for sucrose and saline solutions
      concurrently before being injected with LiCl. They were then re-exposed to both
      solutions, one after injection of vehicle and the other after injection of
      ondansetron. In a choice extinction test on the levers and chains, animals
      performed more of the action whose training outcome was re-exposed under
      ondansetron than the other action, whether the test was conducted after an
      injection of vehicle or after one of ondansetron.

PMID- 7568999
TI  - An associative interpretation of the indirect McCollough effect.
AB  - Following an induction procedure in which a coloured grid is alternated with a
      square of a complementary colour, subjects report colour after-effects on both
      the grid orientation present during induction and the orthogonal non-induced grid
      orientation. The after-effect reported on the induced grid orientation is called
      the McCollough effect (ME). The after-effect reported on the non-induced grid
      orientation is called the indirect ME. There is evidence that the ME represents
      an instance of Pavlovian conditioning. The present results support a conditioning
      interpretation of the indirect ME and are inconsistent with interpretations of
      the indirect ME that attribute the phenomenon to special orthogonal coding
      mechanisms within the visual system.

PMID- 7569000
TI  - Percutaneous ethanol injection therapy for hepatocellular carcinoma: validity of
      MR imaging in the evaluation of treatment effect.
AB  - To evaluate the validity of magnetic resonance imaging for the follow-up of
      percutaneous ethanol injection therapy, 14 patients with a single hepatocellular
      carcinoma lesion smaller than 2.5 cm in diameter underwent MR imaging at 0.5
      Tesla before and after treatment. Posttreatment follow-up examination included
      ultrasonography, contrast-enhanced computed tomography, and fine-needle biopsy in
      all cases. Only one patient showed recurrence within the 12-month follow-up
      period. After treatment, HCC lesions showed hypointensity on T1-, and T2-weighted
      images that lasted 12 months after treatment. In three cases, wedge-shaped
      hyperintense regions peripheral to the HCC nodule were observed after treatment
      on T2-weighted images. Obstructive vasculitis of the portal vein was considered
      to occur as a result of the drainage of ethanol injected in the tumor. These MR
      imaging findings may be helpful in clinical practice.

PMID- 7569004
TI  - Radiotherapy alone for extradural compression by spinal myeloma.
AB  - Between 1976 and 1992, 18 patients with a histologically proven diagnosis of
      plasma cell myeloma (PCM) were treated for palliation of spinal extradural
      compression (EC) by radiotherapy alone. Eighty-five percent of the evaluable
      symptomatic individuals obtained significant pain relief. Ambulatory ability was
      retained or regained in 11 (65%) patients. The overall median period of survival
      was 11 months. Extended median survival was noted in post-treatment ambulatory
      patients (compared with nonambulatory patients) and in individuals whose primary
      presentation of PCM was EC (versus individuals who developed EC during the course
      of the disease). These results suggest that radiotherapy alone may be used in the
      palliative management of patients with EC by PCM.

PMID- 7569002
TI  - Report of a prospective trial--split course versus conventional radiotherapy in
      the treatment of non small cell lung cancer.
AB  - A prospective randomized trial was started in January 1982, to compare morbidity
      and survival of two different radiation regimens for the treatment of non-small
      cell lung cancer (NSCLC). The trial was closed in December 1988. One group of
      patients was treated by conventional daily radiation therapy, and the other group
      by split course therapy. To maintain uniformity, a single physician staged and
      treated all patients and noted morbidity during treatment. Two hundred seventy
      three consecutive lung cancer patients were treated. Only patients who completed
      the full radiation therapy course were included in this study. One hundred
      fourteen patients were treated with split course therapy, and 159 patients were
      treated by conventional daily radiation therapy. A few patients did not return
      for the second course of treatment, which accounts for the different number of
      patients in the two arms of the study. There was no statistically significant
      difference in survival between the two arms. Median survival for the split course
      and the continuous fraction therapy regimens was 11.6 months and 10.9 months,
      respectively. Split course radiation was associated with less morbidity.

PMID- 7569003
TI  - Evaluation of the performance of a whole-body positron imaging system with
      attenuation correction.
AB  - A PET scanner with ring detectors has been modified to accomplish whole-body
      imaging with attenuation correction. To evaluate the performance of this system,
      phantom studies and clinical studies were performed in seven patients. The
      transaxial resolution (FWHM) at the center of the field was 8.6 mm, and the axial
      resolution was 12.3 mm. The counts on the images with attenuation correction were
      linearly related to accumulation of the radiopharmaceuticals, and attenuation
      correction was made accurately. The transmission scan from the top of the head to
      the thigh, about 110 cm in length, required 36 minutes, and one emission scan
      required 18 minutes. The total study time for one transmission scan and three
      sequential emission scans was 1.9 hours. In clinical studies, attenuation
      correction made the discrimination of organs clearer, and would facilitate the
      detection of tumors, especially those in the high attenuation organs or matter.
      The use of this system made it possible to obtain quantitative whole-body
      positron images with adequate diagnostic quality within a reasonable scanning
      time.

PMID- 7569006
TI  - Small cell carcinoma of the prostate: CT and MRI findings.
AB  - We report two cases of small cell carcinoma of the prostate and describe the CT
      and MRI findings, which were primarily based on the rapid growth and high
      metastatic potential of the tumor. CT and MRI are extremely useful for
      demonstration of metastatic lesions. Histological confirmation is needed if the
      findings of CT or MRI are unusual for ordinary adenocarcinoma of the prostate.

PMID- 7569005
TI  - Hepatocellular carcinoma with pyrexia: report of a case.
AB  - Reported here is a case of an unusual type of hepatocellular carcinoma (HCC).
      Since this patient with liver mass exhibited continuous pyrexia, an inflammatory
      pseudotumor or abscess was strongly suspected. Two-phased incremental CT, MR with
      and without Gd-DTPA administration, and angiography demonstrated peripheral
      enhancement of the hepatic mass. Histologically, the tumor proved to be HCC with
      sarcomatoid degeneration. When one encounters a patient with a mass clinically
      and radiologically mimicking an inflammatory pseudotumor or an abscess, poorly
      differentiated HCC with sarcomatoid degeneration should be suspected.

PMID- 7569001
TI  - Three-dimensional display of the bronchi using helical CT.
AB  - The purpose of this study was to evaluate the clinical usefulness of three
      dimensional (3D) images of the bronchi obtained using helical CT. Thirteen
      patients with lung cancer, one with tracheal diverticulum, and one with bronchial
      amyloidosis were examined. The CT scanner employed was the Toshiba Xforce. The
      helical CT scan cycle consisted of 20 continuous rotations, each requiring 1.5
      sec, for a total scanning time of 30 sec. Scans were obtained using a 5-mm X-ray
      beam width, a 5-mm/1.5 sec couchtop sliding speed, and a 2-mm reconstruction
      interval. 3D images were reconstructed using a CEMAX VIPstation. The optimal
      lower and upper threshold CT values for 3D images of the bronchi were -650 and 
      100 HU, respectively, and 3D images clearly depicted endobronchial lesions.
      Cartilage crescents were also demonstrated, but longitudinal and circular mucosal
      folds could not be visualized. In conclusion, 3D images of the bronchi acquired
      using helical CT were useful in evaluating endobronchial lesions.

PMID- 7569008
TI  - Iodide mumps after contrast enhanced CT with iopamidol: a case report.
AB  - We have experienced a case of iodide mumps after CT examination with 100 ml of
      iopamidol. The patient was a 70-year-old woman with a history of right
      nephrectomy due to right renal cancer. She underwent CT examination to explore
      local recurrence and abdominal metastases including lymph node and liver
      metastases. Three hours after the CT examination, she complained of nausea,
      vomiting, facial flushing, bilateral jaw pain, and fever. The laboratory findings
      12 hours after CT examination showed increased white blood cells and elevated
      serum amylase enzyme. Analysis of the amylase fraction showed that 86% originated
      from the salivary glands. She was admitted to the hospital, and the symptoms
      continued for four days, with decreasing severity. Anti-inflammatory therapy was
      performed, and the patient was discharged six days after the event.

PMID- 7569007
TI  - MRI of malignant melanoma of liver.
AB  - We report MR images of primary malignant melanoma of the liver. The tumor showed
      heterogeneously increased signal intensity on both T1- and T2-weighted images.
      After the administration of gadolinium-DTPA, the lesion presented irregular
      enhancement. Autopsy revealed a large black mass surrounded by fibrous tissue.
      The tumor consisted of atypical cells with melanin pigment, and had intratumoral
      degeneration, necrosis, and hemorrhage.

PMID- 7569010
TI  - About tolerance and quality. An important notice to all radiation oncologists.

PMID- 7569011
TI  - EORTC Late Effects Working Group. Late effects toxicity scoring: the SOMA scale.

PMID- 7569009
TI  - Intraarterial infusion of cisplatin with and without preoperative concurrent
      radiation for urinary bladder cancer: a preliminary report.
AB  - We evaluated the clinical efficacy of treating urinary bladder cancer by
      intraarterial infusion of cisplatin using an implanted reservoir with and without
      preoperative concurrent radiation. No previous reports have compared the results
      obtained by these two methods of treatment. Twenty-three patients with bladder
      cancer were treated by intraarterial infusion of cisplatin using an implanted
      reservoir with (n = 13) and without (n = 10) concurrent radiation. The cisplatin
      plus radiation group received intraarterial cisplatin at a total dose of 200-400
      mg and concurrent radiation to a total dose to 30 Gy. The cisplatin group
      received intraarterial cisplatin at a total dose of 100-600 mg. In the cisplatin
      plus radiation group, the overall tumor response rate was 92%. Seven of 13 (53%)
      patients obtained complete response (CR), and the 2-year actuarial survival rate
      was 92%. Only one of the seven complete responders has had a local recurrence. In
      the cisplatin group, the overall tumor response rate was 90%. Four of 10 (40%)
      patients obtained CR, and median survival was 8 months. Three of the four
      complete responders have had local recurrence. There was no significant
      difference between these two groups in the frequency of side effects. Concurrent
      radiation therapy with intraarterial cisplatin resulted in a very low rate of
      recurrence of bladder cancer compared with intraarterial cisplatin therapy alone.
      This method was useful for urinary bladder cancer and may become the treatment of
      choice for this type of cancer.

PMID- 7569012
TI  - LENT SOMA tables.

PMID- 7569013
TI  - Late effects consensus conference: RTOG/EORTC.

PMID- 7569014
TI  - Quality assurance in radiotherapy. European Society for Therapeutic Radiology and
      Oncology Advisory Report to the Commission of the European Union for the 'Europe
      Against Cancer Programme'.
AB  - This document is now in the process of being endorsed by all National Scientific
      Societies of Radiotherapy and Medical Physics of the European countries. It can
      therefore not be formally considered as the definitive version and is still
      susceptible to benefit from further alterations or improvements.

PMID- 7569015
TI  - A quality assurance system based on ISO standards: experience in a radiotherapy
      department.
AB  - The European radiotherapy society has for many years had a great interest in
      quality assurance. The EORTC radiotherapy group has put enormous effort into its
      quality assurance programmes. However, besides programmes for dosimetry and guide
      lines for infrastructure, the organisation of a department should also be subject
      to a quality assurance system. In 1992, in the radiotherapy department in Leiden,
      a project was started to develop a quality assurance system based on the so
      called ISO 9001 quality standards. This paper describes how these standards can
      be applied to create a quality assurance system in a hospital department.

PMID- 7569016
TI  - EORTC Late Effects Working Group. Overview of late effects normal tissues (LENT)
      scoring system.

PMID- 7569018
TI  - Prognostic factors in patients with cervix cancer treated by radiation therapy:
      results of a multiple regression analysis.
AB  - A retrospective analysis of 965 patients with invasive cervix cancer treated by
      radiation therapy between 1976 and 1981 was performed in order to evaluate
      prognostic factors for disease-free survival (DFS) and pelvic control. FIGO stage
      was the most powerful prognostic factor followed by radiation dose and treatment
      duration (P values = 0.0001). If the analysis was limited to patients treated
      with radical doses of 75 Gy or more, dose was no longer significant. Young age at
      diagnosis, non-squamous histology and transfusion during treatment were also
      adverse prognostic factors for survival and control. Para-aortic nodal
      involvement on lymphogram was associated with a reduction in DFS (P = 0.0027),
      whereas pelvic lymph node involvement alone was not. In patients with Stage I and
      IIA disease, tumour size was the most powerful prognostic factor for survival (P
      = 0.0001) and the extent of pelvic sidewall involvement was significant in
      patients with Stage III tumours (P = 0.007). Histological grade appeared to be a
      predictive factor but was only recorded in 712 patients. These features should be
      considered in the staging of patients and in the design of clinical trials.

PMID- 7569017
TI  - The EORTC randomized trial on three fractions per day and misonidazole in
      advanced head and neck cancer: prognostic factors.
AB  - In trial no. 22811 on a randomized comparison of multiple fractions per day
      (MFD), with or without misonidazole, to conventional fractionation in advanced
      head and neck cancer, a large number (523) of patients was entered in a short
      period of time. No differences in treatment results were obtained, but the study
      created an important database, allowing for detailed evaluation of the most
      important factors influencing prognosis. In univariate analysis, factors
      significantly influencing survival and locoregional control were: performance
      status, histological differentiation, tumor site, tumor and nodal staging, and
      tumoral and nodal volume. In multivariate analysis, significant factors for
      survival were nodal involvement, tumor stage, performance status, and tumor site.
      Significant factors for locoregional control were nodal involvement and total
      tumor burden. This analysis suggests that total tumor burden (volume) should be
      included in the interpretation of treatment results in head and neck cancer.

PMID- 7569019
TI  - Conventional radiotherapy combined with carbogen breathing and nicotinamide for
      malignant gliomas.
AB  - High grade malignant gliomas are among the most radioresistant human tumors and
      total doses up to 80 Gy are inadequate to achieve long-term local control in most
      of the patients. Hypoxia has been demonstrated in primary brain tumors and may be
      one of the reasons for their radioresistance. In experimental models carbogen
      breathing and nicotinamide have been shown to act against hypoxia by different
      mechanisms and both modalities were tested in 16 patients with supratentorial
      malignant gliomas in combination with a conventional radiotherapy scheme (50 Gy
      in 25 daily fractions). The present study was performed to determine the
      feasibility and toxicity of conventional radiotherapy combined with carbogen
      breathing and nicotinamide. The unexpectedly high incidence of acute liver
      toxicity, the possible increase of subacute and late CNS toxicity, and the
      absence of a higher effectivity led us to reconsider this new treatment modality
      for patients with malignant gliomas.

PMID- 7569022
TI  - Hyperbaric oxygen as a prophylaxis for radiation-induced delayed enteropathy.
AB  - This trial was accomplished in C3H mice to determine whether hyperbaric oxygen
      (HBO) could be administered to prevent delayed radiation enteropathy. Fifty mice
      randomized into two equal groups received 30 Gy abdominopelvic irradiation in 10
      fractions. The study group received a course of 30 HBO treatments beginning 7
      weeks after the radiation exposure. The control group received only housing and
      nutritional support after irradiation. A third group of three animals had no
      radiation or HBO. All animals were sacrificed 7 months after radiation. Animals
      were inspected grossly for signs of enteropathy. In addition, a special stretch
      apparatus was used to quantify narrowing and rigidity of ileum just proximal to
      the ileocecal junction. Those animals who received HBO had fewer gross signs of
      enteropathy and had less narrowing and less rigidity in their harvested bowel
      segments. These differences were highly statistically significant. Treatment with
      HBO drastically reduces signs of radiation enteropathy. Further study including
      clinical trials are recommended.

PMID- 7569023
TI  - An ICRU 50 radiotherapy treatment chart.
AB  - We illustrate a radiotherapy treatment chart elaborated to fulfil the necessity
      for clarity in reporting information about radiotherapeutic treatment. The
      schematic configuration of the chart results from the experience and the
      cooperation of physicists, physicians and technicians, and an effort has been
      made to satisfy Levels 2/3 of the ICRU 50 recommendations. The chart has been
      divided into four sections corresponding to different kinds of information: a
      cover sheet, a section containing data about the treatment planning geometry and
      the console parameters adopted, a section showing dosimetric data, and a section
      showing treatment data. The chart seems to give a good level of accuracy in
      reporting treatment plan information.

PMID- 7569021
TI  - Acute reaction parameters for human oropharyngeal mucosa.
AB  - The purpose of this study was to determine the influence of changes in dose rate
      over the range 0.8-240 Gy/h on acute oropharyngeal mucosal reactions in human
      subjects, and to estimate the values of the important parameters that influence
      these reactions. Sixty-one patients requiring radiotherapy to palliate incurable
      head and neck cancer were treated on a telecaesium unit, using opposing lateral
      portals to total midline doses, varying between 30 and 42 Gy in 10 daily
      fractions over 2 weeks, at dose rates of 0.8, 1.8, 3.0 and 240 Gy/h according to
      a central composite study design. The severity and time course of reactions were
      charted at least twice weekly for each patient, using the EORTC/RTOG acute
      mucosal reaction grading system. Duration of reaction at each grade was observed
      to provide a more sensitive reflection of effect than the proportion of patients
      reaching any particular reaction grade. Analysis of duration by direct and
      indirect methods suggest alpha/beta ratios in the range 7-10 Gy and half-time
      (t1/2) values in the range 0.27-0.5 h, if mono-exponential repair kinetics are
      assumed. The t1/2 values are short and raise the question as to whether the
      repair kinetics of this tissue are well described by a mono-exponential function.
      Further prospective studies involving multiple daily fraction treatment regimes
      delivered at high dose rate, in which interfraction interval is deliberately
      varied, are needed to find out whether the parameters derived from this project
      are applicable to fractionated treatment courses at high dose rate.

PMID- 7569024
TI  - Reproducibility of patient positioning during routine radiotherapy, as assessed
      by an integrated megavoltage imaging system.
AB  - A portal imaging system has been used, in conjunction with a movie measurement
      technique to measure set-up errors for 15 patients treated with radiotherapy of
      the pelvis and for 12 patients treated with radiotherapy of the brain. The pelvic
      patients were treated without fixation devices and the brain patients were
      treated with individually-moulded plastic shells. As would be expected the brain
      treatments were found to be more accurate than the pelvic treatments. Results are
      presented in terms of five error types: random error from treatment to treatment,
      error between mean treatment position and simulation position, random simulation
      error, systematic simulator-to-treatment errors and total treatment error. For
      the brain patients the simulation-to-treatment error predominates and random
      treatment errors were small (95% < or = 3 mm, 77% < or = 1.5 mm). Vector
      components of the systematic simulation-to-treatment errors were 1-2 mm with
      maximal random simulation error of +/- 5 mm (2 S.D.). There is much interest in
      the number of verification films necessary to evaluate treatment accuracy. These
      results indicate that one check film performed at the first treatment is likely
      to be sufficient for set-up evaluation. For the pelvis the random treatment error
      is larger (95% < or = 4.5 mm, 87% < or = 3 mm). The systematic simulation-to
      treatment error is up to 3 mm and the maximal random simulation error is +/- 6 mm
      (2 S.D.). Thus corrections made solely on the basis of a first day check film may
      not be sufficient for adequate set-up evaluation.

PMID- 7569020
TI  - Prognostic impact of transurethral resection on patients irradiated for localized
      prostate cancer.
AB  - The prognosis for irradiated patients with localized prostatic carcinoma
      following transurethral resection of the prostate (TURP) has been debated.
      Controversy centers upon whether or not TURP has an adverse effect on the
      outcome. A retrospective analysis of 264 patients treated during 1974-1991 with
      radical external beam radiotherapy was performed. Ten patients who were
      irradiated postoperatively were excluded. One hundred and nine patients with
      urinary obstruction underwent TURP. In another 155 patients, pathological
      diagnosis was made by needle aspiration or tru-cut biopsies. One hundred and one
      patients received endocrine manipulation, 58 (40%) in the needle biopsy group,
      and 43 (39.5%) in the TURP group. Lymph node staging by pelvic lymphadenectomy
      (20 cases), lymphangiography (15 cases), and CAT and/or NMR (113 cases) was
      performed in 148 patients. Nodal metastases were found in 38 patients, 19 in the
      needle biopsy group, and 19 in the TURP group. Disease-related, disease-free and
      metastasis-free survivals were calculated for all stages and within each tumor
      stage and histological grade for both groups. Correlation of pretreatment factors
      with clinical outcome was evaluated by multivariate analysis. Overall, disease
      related survival was significantly higher (P = 0.05) in patients undergoing
      needle biopsy than in those who had TURP (58% vs. 38% at 10 years). This
      difference was more significant in the subset of patients with well
      differentiated tumors (P < 0.01). However, no difference could be observed
      between the two groups in histological grade 2 and 3 tumors or by stage
      comparison.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569025
TI  - Rebuttal: is gambling a serious alternative to evidence-based medicine?

PMID- 7569026
TI  - The dosimetric effects of asymmetric megavoltage beams.

PMID- 7569027
TI  - An equation for the dose response of radiation-induced apoptosis.

PMID- 7569028
TI  - Block scatter in photon fields.

PMID- 7569029
TI  - Cellular basis of radiation-induced fibrosis.
AB  - Fibrosis is a common sequela of both cancer treatment by radiotherapy and
      accidental irradiation and has been described in many tissues including skin,
      lung, heart and liver. The underlying mechanisms of the radiation-induced
      fibrosis still remain to be resolved. In the present review we tried to
      illustrate the basic cellular mechanisms of radiation-induced fibrosis based on
      the newest findings arising from molecular radiobiology and cell biology. Based
      on these findings the cellular mechanism of radiation-induced fibrosis can be
      seen as a multicellular process involving various interacting cell systems in the
      target organ resulting in the fibrotic phenotype of the fibroblast/fibrocyte cell
      system.

PMID- 7569030
TI  - The EORTC randomized trial on three fractions per day and misonidazole (trial no.
      22811) in advanced head and neck cancer: long-term results and side effects.
AB  - From 1981 to 1984, a randomized study was done by the EORTC Radiotherapy Group
      comparing a fractionation schedule with three fractions per day (multiple
      fractions per day, MFD), with or without misonidazole, to conventional
      fractionation. The aim of the study was to obtain improved local and regional
      control and survival by shortening of the treatment time in the first 2 weeks of
      irradiation. Three fractions of 1.6 Gy/day (4-h interval) were given during 10
      irradiation days to a total of 48 Gy. After 3-4-weeks interval, a boost was given
      to 67.2 or 72 Gy also in three fractions per day. This schedule was compared to
      an identical arm with misonidazole 1 g/m2/day and a third arm with conventional
      fractionation (70 Gy in 35 fractions, 7 weeks or 75 Gy in 44 fractions, 9 weeks).
      A total number of 523 patients was included in the study. Acute mucositis was
      much heavier in patients treated with three fractions per day (Van den Bogaert et
      al. Int. J. Radiat. Oncol. Biol. Phys. 8: 1649-1655, 1982). Early results,
      communicated in 1986 (Van den Bogaert et al. Int. J. Radiat. Oncol. Biol. Phys.
      12: 587-591, 1986) showed no differences in treatment outcome between the three
      treatment arms. Long-term results and data on late effects are now available.
      Survival at 5 years was 18% (SE 1.9%) and locoregional control was 27% (SE 2.9%).
      No statistically significant differences could be observed between the three
      treatment arms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569031
TI  - Papers from a symposium on embryonic stem cells and transgenic livestock.
      Melbourne, Australia, 12 January 1994. Symposium dedicated to Julian Wells.

PMID- 7569032
TI  - Studies of in vitro differentiation with embryonic stem cells.
AB  - Embryonic stem (ES) cells were first cultured from mouse embryos little more than
      a decade ago, yet they are now widely used in transgenic studies which are
      revolutionizing mammalian genetics. Although drawing less attention, in vitro
      studies of mouse ES cells have also contributed widely to the understanding of
      mechanisms of embryonic cell differentiation and proliferation. This review
      focusses on the application of ES cells as in vitro models for cellular and
      molecular events in the early mammalian embryo. Future studies with cultured ES
      cells of mouse and other species should provide insights into the factors
      regulating the differentiation of intermediate stem cells and terminal cells for
      the various embryonic lineages, thus contributing profoundly to the understanding
      of mammalian embryogenesis as well as providing cells for therapeutic
      applications.

PMID- 7569033
TI  - Systems for production of calves from cultured bovine embryonic cells.
AB  - The development of totipotent bovine embryonic cell cultures has great value in
      cattle breeding. They provide: (1) a mechanism for making large numbers of clonal
      offspring by nuclear transfer; (2) an efficient gene transfer system through the
      use of selectable markers to select transgenic cells; and (3) a mechanism for
      site-specific gene transfer or deletion by homologous DNA sequence recombination.
      Bovine embryonic cell cultures have been established from blastocyst inner cell
      mass (ICM) cells, morulae and the precompaction 16-20-cell stage. All have
      exhibited similar morphology to mouse embryonic stem (ES) cells, pluripotency on
      differentiation and proliferation in culture. Culture systems have consisted of
      microdrop loose suspension short-term cultures or long-term cultures on bovine or
      murine fibroblast feeder layers, in either a microdrop or a culture dish. The
      relative merit of culture systems or media requirements for mitosis and
      prevention of differentiation have not been determined. At present, totipotency
      is also unknown for cultured cells of the 16-20-cell stage. For cultured ICM
      cells, totipotency was demonstrated by the birth of four calves from ICM cells
      cultured 27 days or less in a loose suspension microdrop. Advanced pluripotency
      and perhaps totipotency was demonstrated in one fetus in a recently reported
      study where morulae cells cultured in vitro were chimaerized with non-cultured
      cells. DNA fingerprinting to associate cell lines with offspring and karyotyping
      to ascertain chromatin normalcy is important in ES cell research. Data pertaining
      to the use of each are presented.

PMID- 7569035
TI  - Strategies for the isolation and characterization of bovine embryonic stem cells.
AB  - The practical application of advanced breeding technologies and genetic
      manipulation of domestic animals is dependent on the efficient and routine
      isolation of embryonic stem (ES) cell lines from these species. ES cell lines of
      proven totipotency have thus far been isolated only from the mouse. Murine ES
      cells can be identified by a number of criteria including morphology and
      characteristics in culture, the presence of specific markers, differentiative
      capacity and contribution to chimaeras. Reported cell lines derived from ruminant
      preimplantation embryos do not stably exhibit these characteristics. As
      demonstrated for the mouse, primordial germ cells may provide an alternative
      source for pluripotential cell lines. The isolation, culture and preliminary
      characterization of bovine primordial germ cell-derived (PGCd) cells are
      described in this paper. The PGCd cells are capable of differentiation in vitro
      and display murine ES cell markers including alkaline phosphatase. With farm
      animals, long generation intervals and small numbers of offspring make it
      important to develop techniques for evaluating chimaeric embryos in vitro before
      embarking on expensive in vivo programmes. A method for labelling putative
      pluripotential cells with a fluorochrome marker to follow the fate of such cells
      was developed. Labelled PGCd cells were injected into blastocysts and the
      chimaeric embryos were monitored in vitro. Preliminary results demonstrate that
      the labelled PGCd cells incorporate preferentially within the inner cell mass of
      the host blastocyst.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569034
TI  - Development and validation of swine embryonic stem cells: a review.
AB  - The establishment of embryonic cell lines from swine should be useful for studies
      of cell differentiation, developmental gene regulation and the production of
      transgenics. This paper summarizes the establishment of porcine (Sus scrofa)
      embryonic stem (ES) cell lines from preimplantation blastocysts and their ability
      to develop into normal chimaeras. ES cells can spontaneously differentiate into
      cystic embryoid bodies with ectodermal, endodermal, and mesodermal cell types.
      Further, culture of ES cells to confluence or induction of differentiation with
      retinoic acid or dimethylsulfoxide results in morphological differentiation into
      fibroblasts, adipocytes, and epithelial, neuronal, and muscle cells. These ES
      cells have a normal diploid complement of 38 chromosomes. Scanning electron
      microscopy of the ES cells reveals a rounded or polygonal, epithelial-like cell
      with numerous microvilli. The differentiation of these embryonic cell lines into
      several cell types indicates a pluripotent cell. Furthermore, chimaeric swine
      have been successfully produced using such ES cells.

PMID- 7569036
TI  - Germ line transmission of yeast artificial chromosomes in transgenic mice.
AB  - Several groups have recently reported the successful generation of transgenic
      mice harbouring yeast artificial chromosomes (YACs). Different methodological
      approaches have been shown to produce similar results, namely, the faithful
      expression of the transgenes carried on YAC DNA. In this paper, we compare the
      reported techniques for obtaining transgenic mice carrying YACs using a 250-kb
      YAC bearing the mouse tyrosinase gene. These methods include: microinjection of
      gel-purified YAC DNA into pronuclei of fertilized mouse oocytes, yeast
      spheroblast fusion with embryonic stem (ES) cells and lipofection of YAC DNA into
      ES cells. Taken together, these reports show that the delivery of large genomic
      regions covering a gene of interest (such as those cloned in YAC vectors) is
      feasible, and will ensure appropriate temporal and spatial expression of the
      transgene at a level comparable to that of the endogenous counterpart.

PMID- 7569037
TI  - Site-specific transgene insertion: an approach.
AB  - Methods to improve the production of transgenic animals are being developed.
      Conventional transgenesis, involving microinjection of DNA into fertilized eggs,
      has a number of limitations. These result from the inability to control both the
      site of transgene insertion and the number of gene copies inserted. The approach
      described seeks to overcome these problems and to allow single copy insertion of
      transgenes into a defined site in animal genomes. The method involves the use of
      embryonic stem cells, gene targeting and the FLP recombinase system.

PMID- 7569038
TI  - Chromosomal position effects and the modulation of transgene expression.
AB  - Chromosomal position effects can influence strongly the transcription of foreign
      genes in transgenic animals. This results in low frequencies and levels of gene
      expression and, in some cases, in aberrant patterns of expression. Strategies for
      overcoming these effects are described with particular reference to their
      application in embryonic stem cells.

PMID- 7569041
TI  - Transgenic sheep and wool growth: possibilities and current status.
AB  - Merino wool is the result of generations of selection, yet improvements in wool
      quality and performance are still being sought. Through gene manipulation, sheep
      transgenesis offers possibilities of understanding the relationship between wool
      keratin protein composition and fibre structure and properties and of introducing
      novel changes to fibre properties and growth rates. We have established an
      efficient sheep transgenesis programme with an overall transgenic rate of 2.1% of
      zygotes injected. However, by incorporating in vitro culture and assessment of
      injected zygotes, this equates to a transgenic rate of 13% from 516 lambs born.
      With the first keratin gene construct, a wool keratin type II intermediate
      filament gene, four live F0 transgenic sheep have been produced and all express
      the transgene. In one of them, the highest expressor, phenotypic and
      ultrastructural changes were evident in the fleece. To improve wool growth rate
      by increasing the supply of cysteine to the follicle, transgenic sheep are being
      produced carrying the two genes necessary for endogenous cysteine synthesis.
      Three promoters have been tested driving the cysteine synthesis genes: two
      general promoters, the Rous sarcoma virus long terminal repeat and mouse
      phosphoglycerate kinase promoter, and a rumen-specific promoter from the sheep
      small proline-rich protein gene. To date, one transgenic sheep (bearing the small
      proline-rich protein promoter constructs) has produced cysteine in the rumen,
      although the amount was low at 3 months of age and not detectable at 6 months.

PMID- 7569039
TI  - Mouse testis Pdha-2 promoter upstream sequences confer tissue-and temporal
      specific activity in transgenic mice.
AB  - Spermatogenesis is a complex process requiring the coordinate expression of a
      number of testis-specific genes. One of these, Pdha-2, codes for the murine
      testis-specific isoform of the E1 alpha subunit of the pyruvate dehydrogenase
      complex. To elucidate the mechanisms regulating its expression in vivo, we have
      begun to investigate the Pdha-2 promoter in transgenic mice. In this paper, a
      construct containing 3.0 kb of promoter and upstream sequences is reported to be
      sufficient for directing the testis-specific expression of a CAT reporter gene in
      mice harbouring the transgene. Similarly to the endogenous Pdha-2, the CAT gene
      is expressed in testis in a stage-specific manner. However, the 3.0-kb Pdha-2
      promoter is not active in somatic tissue suggesting that repressor elements may
      be present within these sequences.

PMID- 7569040
TI  - Transgenic strategies to increase disease resistance in livestock.
AB  - Approaches to modify disease resistance or susceptibility by transgenic means
      will be a major asset to animal welfare as well as to the economics of animal
      production. Candidates for gene transfer experiments include all genes known to
      influence non-specific and specific host defence mechanisms against infectious
      pathogens. Additional strategies such as 'intracellular immunization', 'genetic
      and congenital immunization', antisense RNA approaches and targeted disruption of
      disease susceptibility genes promise to gain importance in conferring increased
      disease resistance. The cytokine network regulates cellular viability, growth and
      differentiation in physiological and pathophysiological states. Detailed
      understanding of cytokine signal transduction pathways and transcriptional
      activators will provide not only new target molecules for modulating the immune
      response but will also facilitate the elucidation of host-pathogen interactions.

PMID- 7569042
TI  - Strategies for production of pharmaceutical proteins in milk.
AB  - Although it is only a decade since the use of transgenic livestock for the
      production of pharmaceutical proteins in milk was first suggested, great progress
      has been made. There is every reason to expect that, as methods for the transfer
      of genomic clones are applied with efficient regulatory elements, many proteins
      will be produced at high concentrations in the milk of livestock species. In most
      cases, these proteins will be biologically active, however, it remains to be
      shown whether they will be identical in structure and function to the natural
      product.

PMID- 7569043
TI  - Virus-vectored immunocontraception for control of wild rabbits: identification of
      target antigens and construction of recombinant viruses.
AB  - The need to control animal populations arises in many situations in the world
      from a variety of motives. Present control strategies are almost universally
      based on lethal procedures. Increasingly, there is dissatisfaction with such
      approaches from many different perspectives. In response to these concerns, the
      concept of controlling populations of pest species through control of their
      fertility has been mooted. Successful examples of this approach exist in cases of
      small, discrete pest populations but application of this to a widely distributed
      species over a broad geographical area has not yet been achieved. In this
      article, we report on a new approach to fertility control, virus-vectored
      immunocontraception, and discuss its applicability to control of wild rabbit
      populations. Particular emphasis is placed on the strategy for selection of a
      target molecule capable of inducing an immunocontraceptive response and on how
      the gene encoding such a molecule might be engineered into the myxoma virus for
      distribution into the population. The fact that the procedures for antigen
      identification and the viral engineering methods used are, to varying extents,
      generic means that the broad principles of this approach are applicable in other
      species.

PMID- 7569044
TI  - Transgenic livestock as genetic models of human disease.
AB  - Genetic models of human disease can lead to new insights concerning disease
      aetiology or suggest novel therapeutic interventions. Livestock species,
      especially pigs, cows, sheep and horses, are often good animal models of human
      disease. However, genetic models in livestock species have included only the
      study of spontaneous mutations. Production of transgenic livestock is now
      possible but owing to a low efficiency of production, it is very expensive and
      its application limited. Anticipated application of improved technologies such as
      embryonic stem cells and homologous recombination will allow for increased
      sophistication of experimental design and wider use of genetically modified
      livestock. In all cases, the appropriate species for a genetic model of human
      disease should be the species which best models the physiology of the organ or
      system under consideration. In the future, livestock will play an increasingly
      more important role in biomedical research through the application of genetic
      engineering methodologies.

PMID- 7569046
TI  - Progress and emerging problems in livestock transgenesis: a summary perspective.
AB  - The creation of transgenic livestock is a complex multistep procedure the
      successful execution of which demands a high level of skill and application.
      Useful animals have been generated by transfer of genes to zygotes by
      microinjection, but further extension to livestock breeding is severely limited
      by the present low efficiency and lack of precision in gene transfer procedures.
      There are major developments in alternative approaches to gene transfer and those
      based on embryonic stem (ES) cell lines show particular promise as a broadly
      adaptable means of allowing precise manipulation of specific genes within the
      animal genome. Rapid progress is being made in adapting ES cell technology to
      livestock species but as yet no one has demonstrated the totipotency of the
      putative cell lines so far generated. The demonstration of the feasibility of the
      chimaeric route for reinstating an ES cell genome into the germ line of the pig
      is a major advance. For other livestock breeds, particularly those with long
      generation times and bearing single young where the chimaeric route is much less
      useful, there are encouraging developments in nucleus transfer (cloning)
      technology which could provide practical solutions. Overall, there are now good
      reasons to be optimistic that transgenesis will eventually be available to all
      livestock breeders with the proviso that there are no further unanticipated
      phenomena such as the effect of tissue culture on imprinting, to be discovered to
      threaten the predictability of outcome of ES cell-derived pregnancies and further
      limit the potential usefulness of this futuristic technology to the livestock
      industry.

PMID- 7569047
TI  - Timing of seasonal breeding in birds, with particular reference to New Zealand
      birds.
AB  - A model to explain the timing of seasonal breeding in birds is presented. It is
      assumed that, despite the wide range in egg-laying seasons, there are common
      physiological mechanisms which underlie seasonality in birds and that most, if
      not all, birds are photoperiodic. Birds are considered to possess an internal
      rhythm of reproduction which is synchronized with seasonal changes in the
      environment by external factors, particularly the annual cycle of daylength. The
      rhythm consists, at least in part, of regular changes in the photoperiodic
      response between states of photosensitivity and photorefractoriness. Avian
      breeding seasons effectively start in autumn when birds become photosensitive,
      regardless of when egg-laying occurs. The timing of breeding is then influenced
      by the rate of increase of hypothalamic 'drive' and by the sensitivity of the
      hypothalamus and pituitary gland to inhibitory feedback from gonadal steroids. If
      sensitivity is high, gonadal growth will not occur until the threshold daylength
      for photostimulation is exceeded after the winter solstice. Egg-laying then
      starts in late winter, spring or summer. Alternatively, steroid feedback may be
      relatively low and gonadal growth may be sufficiently rapid once the birds become
      photosensitive that breeding occurs in late autumn or winter. The time of egg
      laying in birds may also be strongly influenced by supplementary information,
      such as social cues, food availability, temperature and rainfall and, in some
      species, this information is more important than daylength in determining the
      timing of breeding. The review also includes the first summary of the breeding
      seasons of New Zealand birds. The pattern of egg-laying is exactly the same in
      native birds, in birds introduced to New Zealand and in other Southern hemisphere
      birds from similar latitudes, with a broad peak of egg-laying occurring from
      September to December. In addition, annual cycles of steroid hormone
      concentrations in the North Island brown kiwi, the yellow-eyed penguin and the
      kakapo are consistent with results from many studies on Northern hemisphere
      birds. This model for the timing of breeding in birds can be applied to New
      Zealand birds and it is concluded that the physiological control mechanisms for
      the timing of seasonal breeding in New Zealand birds are similar to those of
      other birds.

PMID- 7569045
TI  - Challenges and progress in the production of transgenic cattle.
AB  - The production of transgenic cattle presents a number of unique challenges not
      encountered in other species. First, the survival of microinjected zygotes is
      low; only 15% in vivo-derived develop into morulae and blastocysts and, of these,
      only about 18% yield live calves. Second, transgene integration frequency is
      relatively low, around 3%. Thus, more than 1000 zygotes must be injected to
      produce a single transgenic calf. Obtaining sufficient zygotes from donor cattle
      to sustain a transgenic cattle programme is logistically and financially
      prohibitive, since the average superovulated donor yields only about four
      microinjectable zygotes per collection attempt. In vitro oocyte maturation and
      fertilization techniques may be used to alleviate this problem, although
      initially the developmental potential of in vitro-derived microinjected zygotes
      is lower than their in vivo-produced counterparts (8% v. 15%, respectively, yield
      morulae and blastocysts). Since only 3-5% of calves born from microinjected
      zygotes produced in either fashion yield transgenics, at least 20-30 pregnancies
      must be carried to term for every transgenic calf born. These conditions require
      that large herds of donor and recipient cattle be maintained. Recipient
      requirements could be reduced if transgene integration frequency could be
      increased, but improvements in the near future are unlikely since the mechanism
      of integration after pronuclear microinjection is poorly understood.
      Alternatively, embryos could be screened for integrated transgenes before
      transfer; however, efforts in this area have been complicated by high frequencies
      of false positive results. Although yet to be developed, bovine embryonic stem
      cells would alleviate many of these problems and permit a wider range of genetic
      manipulations.

PMID- 7569048
TI  - Inhibition of glyceraldehyde 3-phosphate dehydrogenase in boar spermatozoa by
      bromohydroxypropanone.
AB  - In the presence of 3-bromo-1-hydroxypropanone (BOP), cauda epididymal sperm
      obtained from mature boars produced a carbonyl compound which is assumed to be
      (S)-3-bromolactaldehyde. Glyceraldehyde 3-phosphate dehydrogenase was rapidly
      inhibited which resulted in the accumulation of dihydroxyacetone phosphate and
      fructose-1,6-bisphosphate, and no accumulation of lactate when fructose was the
      substrate. The energy charge potential of the cells declined in the presence of
      BOP when either fructose or glycerol were substrates. It is suggested that BOP is
      transformed into (S)-3-bromolactaldehyde, which is the actual inhibitor of
      glyceraldehyde 3-phosphate dehydrogenase, thus demonstrating BOP to be the first
      brominated chemical to have an anti-glycolytic action on mature sperm in vitro.

PMID- 7569049
TI  - Large equine blastocysts are damaged by vitrification procedures.
AB  - Viability following vitrification of equine blastocysts with different sizes was
      investigated in vitro. Twenty-four blastocysts were classified into three groups
      according to their diameters (< 200 microns, 200-300 microns and > 300 microns; n
      = 8 each). The solution used for vitrification was defined as EFS and contained
      40% ethylene glycol, 18% Ficoll and 0.3 M sucrose in modified-phosphate-buffered
      saline (m-PBS). During pretreatment with 20% ethylene glycol in m-PBS for 20 min,
      the larger blastocysts responded to the osmotic pressure caused by 20% ethylene
      glycol more slowly than the smaller blastocysts. Single blastocysts were loaded
      into the EFS in 0.25-mL straws, left to stand for 1 min and vitrified in nitrogen
      vapour. After thawing for 20 s in water (20 degrees C), a fractured zona
      pellucida or capsule was seen in: 1 of 8 blastocysts < 200 microns in diameter; 1
      of 8 blastocysts 200-300 microns in diameter; and 2 of 8 blastocysts > 300
      microns in diameter. When the blastocysts were cultured for 48 h in TCM199
      supplemented with 10% fetal bovine serum at 37 degrees C in 5% CO2 in air, 7 of 8
      (88%) blastocysts < 200 microns in diameter and 6 of 8 (75%) blastocysts 200-300
      microns in diameter developed with re-expansion of the blastocoele. However, the
      developmental ability of blastocysts > 300 microns in diameter (2 of 8, 25%) was
      significantly lower than that of blastocysts < 200 microns in diameter (P <
      0.05).

PMID- 7569050
TI  - Relationship between testicular morphology and sperm production following
      ischaemia in the ram.
AB  - Arteriosclerosis was induced in the internal spermatic artery of rams to
      determine if this condition is implicated in the aetiology of testicular
      pathology which causes male infertility. Data were collected on sperm
      concentration and motility for 56 days following surgery to provide an index of
      testicular function. Testes were then weighed and a testicular biopsy score count
      was performed on histological sections to assess spermatogenic potential of
      seminiferous tubules. Vascular disturbance caused focal damage of the
      seminiferous epithelium, similar to that seen among infertile men, and a
      reduction in ejaculate volume, sperm concentration and sperm motility. Sperm
      concentration decreased following ischaemia yet was maintained to some degree by
      a germ-cell depleted spermatogenic epithelium. Normal testicular morphology was
      maintained above a testis weight of about 120 g (for an individual testis), but
      below this threshold spermatogenesis was severely impaired. In conclusion, these
      data have provided information on the relationship between testicular morphology
      and function following ischaemia in the ram. Furthermore, the morphological
      changes induced in the testis were similar to those seen among infertile men and,
      by their focal nature, could explain the distinction between oligozoospermia and
      azoospermia in men exhibiting spermatogenic arrest.

PMID- 7569051
TI  - Distribution of variance associated with measurement of post-thaw function in ram
      sperm.
AB  - Post-thaw characteristics of ram semen frozen as pellets were assessed using
      biochemically (amidase activity) or motility-based (Hamilton Thorn Motility
      Analyzer) techniques. The total variation associated with each semen
      characteristic measured was partitioned between rams (5), ejaculates within rams
      (5), pellets within ejaculates (5) and within pellets (2). A variety of variance
      distributions were observed for the characteristics measured. Of the 18 post-thaw
      characteristics examined, 10 had > 50% of variance distributed between within
      ejaculate components. This has important implications for the way in which such
      measurements may be used in post-thaw semen analysis.

PMID- 7569053
TI  - Localization of neutral endopeptidase in the ovine uterus and conceptus during
      the oestrous cycle and early pregnancy.
AB  - Neutral endopeptidase (NEP; EC 3.4.24.11), an enzyme which metabolizes several
      peptides (including oxytocin and endothelins) implicated in the control of
      uterine function, was found to be localized in the ovine uterus throughout the
      oestrous cycle and in the uterus and conceptus during early pregnancy, using
      immunohistochemical techniques. Positive NEP immunoreactivity was found in the
      endometrium principally in stromal cells, in the vasculature in endothelial and
      vascular smooth muscle cells, and also weakly in some glandular epithelial cells.
      In a layer of stromal fibroblasts several cells in thickness underlying the
      luminal epithelium, staining was much weaker than that in the deeper stromal
      cells throughout the period examined. NEP staining was also present in smooth
      muscle cells of the myometrium at all times, and was most intense in the layer of
      cells adjacent to the endometrium. In the conceptus, NEP immunohistochemical
      staining was found in uninucleate cells, but not in binucleate trophoblast cells,
      in epithelial cells of the allantois and amnion, and in the heart and brain of
      the Day-20 embryo. In ovariectomized ewes treated with oestrogen or progesterone
      separately or remaining untreated, immunohistochemical staining of NEP was
      stronger when compared with intact ewes, in caruncular and intercaruncular stroma
      and epithelia, in glands, in the vasculature and in myometrium. The staining was
      less intense in all cell types in ewes receiving oestrogen plus progesterone. The
      expression of NEP and its specific regionalization within the uterus indicate a
      mechanism by which the availability of biologically important peptides involved
      in the regulation of the oestrous cycle and implantation, including oxytocin and
      endothelin, can be controlled by regulation of their metabolism.

PMID- 7569052
TI  - Cellular composition of primary cultures of human granulosa-lutein cells and the
      effect of cytokines on cell proliferation.
AB  - The cellular composition of cells collected from the follicular fluid obtained
      during the IVF procedure and cultured in vitro was examined, as well as the
      effects of two cytokines, interleukin-2 (IL-2) and tumour necrosis factor-alpha
      (TNF alpha), on the proliferation of individual cell types. After 48 h in
      culture, most of the cells were granulosa-lutein cells exhibiting positive
      staining against 3-beta-hydroxysteroid dehydrogenase (3 beta-HSD). About one
      third of the total cell population stained positive with monoclonal antibodies
      against specific antigen sites on lymphohaemopoietic cells, including B
      lymphocytes, T-lymphocytes, natural killer cells, monocytes and macrophages.
      During this 48-h period, IL-2 and TNF alpha significantly (P < 0.05) increased
      the proportion of leukocyte common antigen (LCA)-positive cells and monocytes. At
      the end of 144 h in culture, although LCA-positive cells and monocytes were still
      present, there were fewer. The main targets for the proliferative effects of IL-2
      and TNF alpha in this culture system during the first 48 h are leukocytes rather
      than steroid-producing cells. Thus, any observed effects from the addition of
      cytokines in this system may be due to indirect effects of cytokine-activated
      leukocytes on granulosa-lutein cells.

PMID- 7569054
TI  - Interactions between large and small luteal cells collected during the mid- or
      late-luteal stages of the bovine oestrous cycle.
AB  - The effects of contact between large and small bovine luteal cells together with
      those of luteinizing hormone (LH) or arachidonic acid (AA) on progesterone
      production during the oestrous cycle were investigated. Corpora lutea were
      collected during the mid-luteal stage (Days 10-12; n = 4) and late-luteal stage
      (Days 17-18; n = 4) of the oestrous cycle. Large and small luteal cells were
      dispersed and separated and then incubated together or separately. Mid-luteal
      stage cells were treated with LH (0 or 5 ng) whereas late-luteal stage cells were
      treated with LH (0 or 5 ng) or AA (0 or 10 microM). Culture medium was collected
      and replaced 1, 3 and 6 h after starting treatments. Progesterone production
      decreased (P < 0.0001) with increased incubation time irrespective of cell
      arrangement, the stage of the oestrous cycle or treatment. During the 18 h before
      treatment, cells in the contact arrangement produced more progesterone (P <
      0.003) than cells without contact in both mid- and late-luteal stages of the
      oestrous cycle; progesterone production within cell arrangements between
      prospective treatment groups was similar. After initiating treatments, mid-luteal
      stage cells in the control group without contact produced more progesterone (P <
      0.01) than cells with contact. Mid-luteal stage cells treated with LH produced
      more (P < 0.0001) than control cells; progesterone production between cell
      arrangements within the LH treatment group was similar. In the late-luteal stage
      cells, both LH and AA increased (P < 0.01) progesterone production by comparison
      with control cells; LH and AA treatment groups produced similar results.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7569055
TI  - Characterization of glucose transport in preimplantation mouse embryos.
AB  - Membrane transport of glucose divorced from metabolism, was analysed in 2-cell
      embryos, morulae and blastocysts in the preimplantation mouse. A non
      metabolizable radiolabelled analogue, 3,0 methyl D-glucose (3OMG) was used, and
      glucose was used as well in morulae and blastocysts; incubation times were < or =
      5 min. Uptake occurred by combination of a non-saturable process, resistant to
      cytochalasin-B, and a facilitated process exhibiting classic Michaelis-Menten
      kinetics. The rate constant for the non-saturable component increased from 1.22
      +/- 0.12 pL embryo-1 min-1 in 2-cell embryos to 2.08 +/- 0.44 pL embryo-1 min-1
      in blastocysts, determined using 3OMG. The Km values of the saturable component
      for 3OMG at 22 degrees C were relatively constant at about 6.5 mM in 2-cell
      embryos, morulae and blastocysts. At 37 degrees C, the Km increased from 6 mM in
      2-cell embryos to 17 mM in blastocysts. Vmax increased about five-fold during
      development from the 2-cell stage to the morula stage and about three-fold during
      development to the blastocyst. The Km values for glucose in morulae and
      blastocysts were constant at about 1.3 mM at 37 degrees C. Uptake of 3OMG in
      blastocysts was inhibited by glucose and stimulated by incubation in glucose-free
      medium. There was no kinetic evidence for the participation of multiple saturable
      components in uptake by blastocysts or morulae. This supports the observation
      that the glucose transporter GLUT2, which is first expressed at the 8-cell stage
      to supplement GLUT1 expressed in the oocyte, does not contribute to the uptake of
      environmental glucose and is, therefore, probably restricted in expression to
      abcoelic membrane areas of the trophectoderm. Together with the known values of
      glucose in uterine fluid, the kinetic data indicate that most glucose enters the
      trophectoderm by this GLUT1 at a rate which directly reflects the external
      glucose concentrations. The activity increased on a cellular basis as development
      proceeded, suggesting increased activity to meet the increasing metabolic
      requirements of the blastocyst for glucose.

PMID- 7569056
TI  - Platelet-activating factor-antagonists reduce implantation in mice at low doses
      only.
AB  - The effects of a number of platelet-activating factor (PAF)-antagonists on embryo
      implantation were investigated. Mice were treated from Day 1 to Day 4 of
      pregnancy with three defined PAF-antagonists: SRI 63 441, BN 52021, and WEB 2086.
      Necroscopies were performed on Day 8 and the number of implantation sites, the
      implantation rate (number of implanted embryos compared with the number of
      corpora lutea) and the proportion of animals pregnant were determined. Each agent
      caused a reduction in the number of implantation sites at relatively low doses.
      The dose that had a maximum contragestational effect was 40 micrograms, 10
      micrograms and 10 micrograms (per 30 g bodyweight per day) for SRI 63 441, WEB
      2086 and BN 52021 respectively. This contragestational effect was completely lost
      at twice (SRI 63 441), five times (WEB 2086) and ten times (BN 52021) the most
      effective dose. Treatment with WEB 2086 on the day of implantation (Day 4) by
      intraperitoneal injection or instillation into the uterus only did not
      significantly reduce the implantation rate and neither did treatment after
      implantation (Days 5-8). The results show that the pharmacology of PAF
      antagonists in early pregnancy is not simple. An understanding of the actions of
      these agents in early pregnancy will require a detailed knowledge of their
      pharmacokinetics, pharmacodynamics and targets of action in early pregnancy.

PMID- 7569058
TI  - Effects of tumour necrosis factor alpha (TNF alpha) on ovulation in the rat
      ovary.
AB  - The effects of tumour necrosis factor alpha (TNF alpha) on ovulation rate,
      ovarian secretion of steroids, and on tissue concentrations of the ovulatory
      mediators plasminogen activator (PA) and prostaglandins were examined in rat
      ovaries perfused in vitro for 20 h. Unstimulated control ovaries did not ovulate
      whereas luteinizing hormone (LH; 100 ng mL-1) induced ovulations in all ovaries
      (2.6 +/- 0.7). TNF alpha (40 ng mL-1) induced ovulations in 3 of 5 ovaries (0.8
      +/- 0.4). When TNF alpha was added concomitantly with LH, the LH-induced
      ovulation rate was increased four-fold (10.6 +/- 1.3). This effect was not seen
      when TNF alpha was added 5 h after LH (3.2 +/- 0.6). More progesterone was
      released when TNF alpha was combined with LH by comparison with LH alone. Tissue
      concentrations of prostaglandin F2 alpha (PGF2 alpha) and PGE were increased by
      the addition of TNF alpha when compared with the control group, but did not
      exceed those observed in the LH group, when TNF alpha was combined with LH. PA
      activity in the tissue was unaffected by TNF alpha and the LH-induced increase in
      PA activity was inhibited when TNF alpha was combined with LH. The results
      demonstrate that the proinflammatory cytokine TNF alpha promotes ovulations in
      the rat ovary.

PMID- 7569057
TI  - Inhibitory potency of isoprenaline on guinea-pig and gravid human myometrium
      following extraneuronal uptake blockade.
AB  - The hypothesis that inhibitory effects of isoprenaline on myometrial
      contractility may be constrained by activation of putative intracellular beta
      adrenoceptors negatively-coupled to adenylate cyclase was examined. Field
      stimulated preparations of guinea-pig and human myometrium were used to examine
      the influence of the catecholamine extraneuronal uptake2 inhibitors,
      corticosterone and beta-oestradiol, on the inhibitory effects of the beta
      adrenoceptor agonist, isoprenaline, on uterine contraction. Longitudinal and
      circular myometrial layers were obtained from guinea-pigs in dioestrus, primed
      with oestrogen before progesterone, or pregnant (Days 62-65). In the guinea-pig
      myometrium, corticosterone (30 microM) did not affect responses to isoprenaline.
      beta-oestradiol (10 microM) induced a small potentiation of the effects of
      isoprenaline on longitudinal myometrium from dioestrus guinea-pigs. Myometrial
      preparations were obtained from pregnant women (36-40 weeks gestation) undergoing
      caesarean section. Isoprenaline inhibited stimulation-evoked contractions in 7 of
      10 preparations of the inner myometrial layer and in 5 of 8 preparations of outer
      myometrial layer. Corticosterone (30 microM) reduced the effects of isoprenaline
      on the inner layer and did not affect the outer layer. These results do not
      support the existence of mechanism involving isoprenaline-sensitive intracellular
      receptors which constrain responses to beta-adrenoceptor agonists.

PMID- 7569059
TI  - Comparative response of the immature and mature ovine fetus to corticotrophin
      releasing hormone (CRH).
AB  - The aim of this study was to address the possibility that the low concentrations
      of adrenocorticotrophin (ACTH) seen in the ovine fetus between 90 and 120 days of
      gestation could be attributed to an alteration in the sensitivity or
      responsiveness of the fetal pituitary to corticotrophin-releasing hormone (CRH),
      a key regulator of ACTH secretion. Chronically cannulated ovine fetuses at Days
      104-108 (n = 11, representing fetuses from this 90-120-day period) and Days 138
      142 (n = 6) of pregnancy received graded doses of ovine CRH (0.8, 1.6, 3.8 and
      7.6 micrograms h-1 for 60 min each, given consecutively and in ascending order)
      or isotonic saline (n = 4 at both age groups studied). Arterial blood samples
      were taken concurrently for analysis of plasma immunoreactive CRH, ACTH and
      cortisol throughout the infusion to assess the pituitary-adrenal response.
      Regression lines describing the relationship between log.PCRH and log.PACTH were
      calculated for both age group studied. A significant (P < 0.001) rightward shift
      in the log.PCRH/log.PACTH regression line for the Day 104-108 group was found,
      suggesting that the ovine fetus at this age is less sensitive or responsive to
      exogenous oCRH than the mature Day 138-142 fetus. This decreased responsiveness
      could explain the low concentrations of endogenous ACTH seen during the 90-120
      day period.

PMID- 7569060
TI  - Effect of protein kinase C modulation on gonadotrophin-induced granulosa cell
      steroidogenesis.
AB  - The effect of protein kinase C (PKC) modulation on gonadotrophin-induced ovarian
      granulosa cell differentiation was investigated by using an activator of PKC,
      phorbol 12-myristate 13-acetate (PMA) and inhibitors of PKC, sphingosine (SPH)
      and staurosporine (ST). The effects of PMA (at doses which activate PKC (10 ng mL
      1), and down-regulate PKC (1000 ng mL-1)), sphingosine (25 microM) and
      staurosporine (10(-10)-10(-7) M) on gonadotrophin-induced granulosa cell
      differentiation were studied by the determination of steroidogenesis and cAMP
      accumulation in immature rat ovarian granulosa cells treated with or without
      pregnant mare serum gonadotrophin (100 mU mL-1). PMA (10 ng mL-1) inhibited
      gonadotrophin-induced granulosa cell steroidogenesis and cAMP accumulation. PMA
      (1000 ng mL-1)-induced down-regulation of PKC did not affect gonadotrophin
      induced steroidogenesis. The inhibitory effect of PMA (10 ng mL-1) on
      gonadotrophin-induced granulosa cell steroidogenesis was not present in PKC-down
      regulated cells. These data indicate that PKC activation by PMA inhibits
      gonadotrophin-induced steroidogenesis. SPH also inhibited gonadotrophin-induced
      steroidogenesis and cAMP accumulation. This effect of SPH was not affected by PMA
      induced PKC down-regulation, indicating that this action of SPH does not require
      PKC or is mediated via a phorbol ester-insensitive PKC isoform. ST induced
      steroidogenesis in the absence of gonadotrophin, but was not synergistic with
      gonadotrophin. PMA-induced down-regulation of PKC abolished the effect of ST,
      suggesting that the action of ST requires PKC. The data suggest that ST and PMA,
      which antagonize each other in gonadotrophin-induced steroidogenesis, act via a
      PKC-mediated mechanism whereas the cAMP-associated actions of gonadotrophins and
      SPH are not dependent on PKC.

PMID- 7569063
TI  - Surgery of rectal cancer (technical observations).
AB  - The evolution of the surgical management of rectal cancer is briefly reviewed.
      Factors which influence the choice of the surgical procedure relatively to the
      tumor characteristics, are examined. The role played by preoperative staging as
      the basis of a correct therapeutic approach is underlined. Most common surgical
      procedures in rectal cancer treatment are reported, and emphasis is put on
      aspects of particular interest for radiodiagnosticians and radiotherapists.

PMID- 7569062
TI  - Diagnostic imaging and combined modality therapy of rectal cancer.

PMID- 7569064
TI  - The pathologist's role in the diagnosis and therapy of rectal cancer.
AB  - The pathologist's role in the diagnosis and therapy of rectal cancer is reviewed.
      Basically, it concerns the diagnosis established at biopsy, the staging and the
      definition of prognostic factors. The biopsy-proven diagnosis confirms the
      clinical or radiologic diagnosis of malignancy while the histological type and
      grading is also assessed. The latter includes three levels and is based on the
      tubular clumping of neoplastic cells. The most commonly used staging systems:
      Dukes' classification, TNM, and Jass' system are presented. The staging aspects
      which impact on prognosis are stressed. Particular attention is paid to the
      specific problems of preoperative radiochemotherapy which frequently affects the
      initial grading and staging. Finally, the role the pathologist plays in the
      definition of histopathologic prognostic factors complementary to the
      conventional morphological study, is underlined.

PMID- 7569065
TI  - Rectal exploration in rectal cancer. Double contrast enema vs rectoscopy: a
      comparison of present diagnostic accuracy.
AB  - The present role of rectal exploration in rectal cancer is defined. Indications
      and limitations of endoscopy and radiology in the study of colon relatively to
      the diagnosis and pre-treatment approach to rectal cancer, are reviewed. The need
      to establish definite parameters of tumor morphology indispensable to a correct
      surgical management, to a possible neoadjuvant therapy and to a precise
      assessment of the response to therapy, is emphasized. Compared results about the
      lengthwise tumor extent, the circumferential involvement of rectal walls and the
      distance from the internal anal sphincter, are reported. It is concluded that the
      two diagnostic examinations are complementary and that both represent excellent
      methods for the diagnosis and assessment of the extent of the disease.

PMID- 7569061
TI  - Calicin in human sperm fertilizing zona-free hamster eggs in vitro.
AB  - Calicin, a basic cytoskeletal protein has been proposed to be involved in the
      formation and maintenance of the highly regular organization of the postacrosomal
      perinuclear theca, the calyx of mammalian spermatozoa. The fate of human sperm
      calicin in the zona-free hamster egg fertilized in vitro has been analysed at the
      light and electron microscope level using polyclonal mouse anti-calicin
      antibodies. Calicin was localized in the postacrosomal dense lamina of the
      capacitated acrosome-reacted spermatozoa attached on the surface of the egg as
      well as in the spermatozoa at an early stage of ooplasmic incorporation. As
      determined by the aid of the DNA-specific fluorescent dye 4,6-diamidino-2
      phenylindole (DAPI), the pattern of staining with anti-calicin changed from a
      funnel-shape into a ring soon after the onset of the nuclear decondensation.
      Later, no anti-calicin labelling could be detected around the more decondensed
      sperm nuclei. Because the residual, ring-like accumulation of calicin was
      associated with the least decondensed chromatin, it appears that the degradation
      of calicin-containing perinuclear theca is intimately involved with the
      posteriorly advancing nuclear disintegration. The ring formation also suggests
      that the calyx of human spermatozoa is not structurally homogeneous at least in
      terms of sensitivity to ooplasmic degradation. Calicin appears to be unaffected
      by lytic enzymes of the acrosome. The present study further shows that DAPI can
      be effectively used to analyse sperm nuclear decondensation in vitro.

PMID- 7569066
TI  - The reasoned combined modality imaging of rectal anatomy.
AB  - An accurate analysis of the rectal anatomy and of its "setting" is carried out.
      The various anatomical structures are defined by the available imaging procedures
      to supply information on a reasoned combined modality imaging of rectal anatomy.

PMID- 7569068
TI  - Staging rectal cancer with CT: methodology, signs and parameters.
AB  - Computed Tomography plays a major role in the staging of rectal carcinoma even if
      discordant results are reported in literature. The use of more sophisticated
      procedures has markedly improved its accuracy which is still high in advanced
      tumors and is irreplaceable, though with considerable limitations, in the
      assessment of distant lymphadenopathy. The methods, the indications and
      limitations of computed tomography are reported. Attention is focused on the
      pathological findings for the definition of TNM, which is mandatory to plan a
      correct therapeutic approach.

PMID- 7569069
TI  - Staging rectal cancer with magnetic resonance imaging: methodology, signs and
      parameters.
AB  - Magnetic Resonance Imaging is a rapidly developing procedure suitable for rectal
      cancer staging. Initial results are extremely encouraging in T staging while at
      present this is not so in N staging. MRI is useful in the differentiation between
      stage T2 and T3 because images can be obtained in multiple planes, tissue
      contrast is high and thus scans are always perpendicular to the tumor base.
      However there is a trend to overstaging of rectal cancer frequently due to the
      concomitant perirectal inflammatory reaction. In a near future, the extensive use
      of surface coils will certainly increase spatial resolution with consequently
      improved accuracy.

PMID- 7569067
TI  - Staging rectal cancer with transrectal US: methodology, signs and parameters.
AB  - A review of the literature on the staging of rectal cancer by transrectal
      sonography is presented. T and N accuracy is reported based on the analysis of
      most common sonographic signs and parameters drawn from literature and compared
      to the authors' experience.

PMID- 7569070
TI  - Intraoperative radiation therapy (IORT) in rectal cancer: methodology and
      indications.
AB  - In intraoperative radiation therapy (IORT) a high dose of radiation is delivered
      to the tumor or to the tumor bed, thus favouring local control with no
      significant increase in toxicity. At present it is used to deliver a boost dose
      of radiation for rectal cancer in protocols which include preoperative external
      beam radiation therapy (ERT). From various experiences carried out in a number of
      centers, the technical and methodological features of this procedure have been
      defined also relatively to cost-effectiveness in terms of a longer surgical
      treatment, involved specialized staff and resources. At the 5th IORT
      International Congress held in Lyon in September, 1994, of over 70 clinical
      studies reported, 15 were on rectal cancer with about 700 patients undergoing
      IORT. The growing interest in the use of this procedure in rectal cancer is
      explained by the natural history of the disease, burdened with a high rate of
      local recurrence, and by the possibility of preventing it with high doses of
      radiation. In primary tumors unresectable for cure and in local recurrence it is
      evidenced that ERT+surgery+IORT enable an improvement in local control and
      survival as compared to ERT alone. Results are better when surgery is radical.
      Several studies deal with the role of preoperative combined concomitant
      radiochemotherapy which can favour a radical surgery. A sizeable percentage of
      these patients will present with metastasis, thus adjuvant chemotherapy seems
      suitable. A role of IORT is envisaged also for resectable high risk tumors,
      however results should be confirmed by larger clinical series.

PMID- 7569071
TI  - Concomitant radiochemotherapy in rectal cancer: methodology and indications.
AB  - Concomitant radiochemotherapy (CRC) is based on the administration of
      chemotherapeutic agents concurrently with radiation therapy. It is aimed at the
      spatial cooperation of radiotherapy (ERT) and chemotherapy and the enhancement of
      the local action of radiotherapy. In this study the role of ERT enhancement in
      the treatment of rectal cancer, is analyzed. 5FU is the commonly used drug.
      Clinical and experimental evidence indicates radiotherapy to be enhanced when the
      drug is administered in continuous infusion after radiation and for a suitable
      dose of 5FU. In these conditions, toxicity is usually mild. In contrast, when the
      drug is administered as bolus, the experimental evidence seems to indicate only
      additivity. However the clinical experience has shown an improvement in local
      control and survival at the expense of a higher toxicity. In patients with
      resectable lesions at high risk for local recurrence, randomized CRC studies have
      shown a high rate of local control between 85% and 90%, a 5-year survival between
      55% and 60%, significantly better as compared to control arms: exclusive surgery
      (GITSG7 175), exclusive ERT (NCCTG), bolus CRC (Intergroup). Acute toxicity is
      mostly hematological and gastrointestinal. In patients with lesions unresectable
      for cure, CRC allows high surgical radicality (85-90%). Complete pathologic
      response is 4 to 20%. Local control is high (80-90%) and 3-year survival is 70 to
      90%. Grade 3-4 acute gastrointestinal toxicity was shown to be higher in
      combinations with bolus 5FU. In recurrence CRC has been used for palliation.
      Control of pain to the pelvis was similar to that achieved with radiotherapy
      alone. In a single experience was CRC used preoperatively and results seem
      encouraging.

PMID- 7569073
TI  - [The use of a single anterior oblique field in the treatment of T1aN0 vocal cord
      neoplasms. Results and comparison with other technics].
AB  - From 1985 through 1993, 113 patients affected with T1N0 glottic cancer were
      treated with irradiation alone at the Radiotherapy Department of Umberto I
      Hospital in Mestre, Italy. An anterior oblique beam of 12 MV X-rays (LINAC) or
      gamma-rays of a Cobalt unit were used. Dose distribution was always studied on CT
      scans and with a Theraplan V05-B, Theratronics. Patients age ranged 40-92 years
      (mean: 64.7 years) and they were mostly males. The dose was always 60 Gy/30
      fractions referred to the 90% isodose. The dose to the target volume ranged 90
      105%, with a mean of 99%. The follow-up ranged 26 to 98 months; the median and
      the mean are 38 and 40 months, respectively. Six patients had local relapses and
      were all operated on: cordectomy was performed in 3 of them and laryngectomy in
      the other 3. Radiation therapy yielded 94.7% disease control; the lesion was
      ultimately controlled in 100% of patients after surgical salvage. Fifteen
      patients died, all of them of non-neoplastic disease. The authors compared this
      technique with those most frequently used, i.e., wedged opposed lateral fields
      and wedged anterior oblique beams, and observed that it allows minimal volumes to
      be irradiated with maximal doses and yields results. Wedged beams are not
      necessary with this technique. The authors consider irradiation the treatment of
      choice for early glottic cancer and believe that surgery, with the conservative
      approach if feasible, should be limited to relapses.

PMID- 7569072
TI  - [The SIRM has its own headquarters].

PMID- 7569074
TI  - [Therapeutic implications of the peculiar clinical characteristics of Hodgkin's
      disease in clinical stages I-II with isolated neck presentation].
AB  - Among 703 patients with supradiaphragmatic clinical stages I-II Hodgkin's disease
      consecutively treated 1960 through 1989 at the Florence Radiotherapy Department,
      we identified 98 cases presenting with cervical and supraclavicular nodes
      involvement only. The latter cases were retrospectively reviewed to assess: a) if
      they presented any peculiar clinicopathologic features and b) the possible
      prognostic and therapeutic implications (if any) of these features. The high
      incidence of lymphocytic predominance histology (33%) and Waldeyer's ring (WR)
      involvement (24%) and the very low risk of occult infradiaphragmatic involvement
      (observed in only 2 of 44 patients submitted to staging laparotomy with
      splenectomy, 4.5%) are among the distinctive features of the patients with
      supradiaphragmatic clinical stages I-II Hodgkin's disease. All the 98 patients
      were treated at presentation with irradiation alone. Actuarial cause-specific
      survival 20 years after the end of treatment was 87%; the corresponding value for
      relapse-free survival was 78%. The most frequent complications were irradiation
      pneumonia, most often asymptomatic, and xerostomia. Our data seem to suggest
      that, for the majority of these patients: a) staging laparotomy could be avoided
      and b) "mini mantle" irradiation is an adequate treatment. Moreover, WR
      irradiation could be avoided in the patients without clinical WR involvement.

PMID- 7569075
TI  - [The polycentric multiple arc complanar technic, or telebrachytherapy. A 4-year
      experience (an innovative way for the local control of solid neoplasms)].
AB  - The coplanar polycentric multiple 180 degrees single arc and narrow beams
      technique (PMA) allows high radiation doses to be delivered to the target, with
      similar dose distribution to that of brachytherapy. Since 1990, more than 100
      patients have been treated: 80 had NSCLC, 12 had epidermoid head and neck (oral
      cavity and oropharynx) cancers, 8 brain tumors, 4 esophageal cancers and,
      sporadically, other patients had many other kinds of tumors, e.g., Hodgkin's and
      non-Hodgkin's lymphomas and sarcomas. X photons of a 12-MV Linac have always been
      used. NSCLC patients are assessable for local control, toxicity and survival,
      while the other patients only for local control and/or toxicity. As for 31 stage
      I-II lung cancer patients, CR has been observed in 82.8% of them and PR in 13.8%;
      the response was always assessed with chest radiography, CT, FBS, cytology and/or
      histology. The overall actuarial survival rate is 71% at 40 months, the disease
      free survival rate is 75% and the local progression-free survival rate is 94%. As
      for 49 stage-III patients, CR has been observed in 40% of them and PR in 56%. The
      overall disease-free survival is 10% at 28 months (median survival: 14.37 +/- 0.6
      months). The disease-free survival rate is 23%. The local progression-free
      survival rate is similar to the overall survival rate, which seems to prove the
      very high metastatic spread of this disease in advanced stages. Twelve head and
      neck cancer patients have been treated, 5 of them in stage II and 7 in stage IV.
      CR has been observed in all the patients in lower stages (100%), in 4/7 patients
      in stage IV (57%) and in 4/5 patients (80%) in the T4N0 subgroup. The response of
      brain tumors treated with the PMA technique is difficult to assess because
      radiographic, CT and MR images are difficult to correlate with patients clinical
      status. The patients in our series are still alive, with a medium follow-up of 7
      months (range: 2-16 months). A longer follow-up is necessary before any other
      considerations on the effectiveness of this method can be made. This technique
      was used on the patients who were not eligible for the other techniques with high
      doses delivered to the tumor, because of its volume and/or shape. Four esophageal
      cancers were treated with palliative intent, because of absolute dysphagia, in
      alternative to HDR brachytherapy. All these patients have obtained symptom
      remission.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7569077
TI  - [Perineural metastatic spread along the infraorbital nerve in malignant neoplasms
      of the skin. Findings with computerized tomography and magnetic resonance in 2
      cases].

PMID- 7569076
TI  - [Transcutaneous radiotherapy combined with low dose intraluminal brachytherapy in
      the treatment of non-operable neoplastic stenoses of the bile ducts].
AB  - Percutaneous biliary drainage is an excellent method to relieve the acute
      symptoms related to neoplastic stenoses of extrahepatic bile ducts. However,
      survival rates are low and the quality of life of these patients is poor. High
      dose irradiation--combined with external beams (ERT) and intraluminal
      brachytherapy (BRT) through percutaneous drainage--allows effective disease
      control and, therefore, not only higher survival rates but also a much better
      quality of life when drainage can be removed after bile duct stenosis resolution.
      March, 1990, through March, 1993, eleven patients (8 with extrahepatic
      cholangiocarcinomas and 3 with extrinsic tumors) were treated with combined ERT
      (40-60 Gy, 6-15 MV X-rays) and intraluminal BRT (6-25 Gy, 192Ir wire, LDR). In 8
      patients the biliary stenosis was resolved, completely (CR) in 5 and partially
      (PR) in 3, as shown by posttreatment cholangiography. In 5 patients biliary
      drainage could be removed for an average 9 months' period; 3 of 11 patients did
      not respond to treatment at all (NR). Average overall survival was 14 months: 11
      months for NR patients and 16.5 months for CR+PR patients. Treatment
      complications were acceptable: in two patients only treatment had to be
      discontinued, both during BRT. Two cases of high grade postirradiation stenosis
      were observed, both resolved with percutaneous cholangioplasthy.

PMID- 7569080
TI  - [Stress fractures of the upper third of the tibial shaft in young people. Review
      of radiologic findings and MR in 3 cases].

PMID- 7569078
TI  - [Traumatic lesion of the rotator cuff: ultrasonographic diagnosis. Report of a
      case].

PMID- 7569079
TI  - [Agenesis of the anterior cruciate ligament. Report of a case and review of the
      literature].

PMID- 7569081
TI  - [Diagnosis with ultrasonography and computerized tomography in a case of empyema
      necessitatis of tubercular nature].

PMID- 7569082
TI  - [Mediastinal abscess. Importance of computerized tomography (a case)].

PMID- 7569083
TI  - [Diagnosis with magnetic resonance of rupture of the interventricular septum in
      acute myocardial infarction. Report of a case].

PMID- 7569084
TI  - [Fissured aneurysm of the superior mesenteric vein. Report of a case].

PMID- 7569085
TI  - [Giant gastric leiomyoma. Report of a case].

PMID- 7569086
TI  - [Abdominal granulomatosis with disseminated hepato-splenic lesions from suspected
      cat scratch disease].

PMID- 7569087
TI  - [Muscular idiopathic hypertrophy of the esophagus. Spiral CT findings in a case].

PMID- 7569090
TI  - [Trans-catheter arterial embolization in a case of spontaneous rupture of
      hepatocarcinoma].

PMID- 7569088
TI  - [Ureteral metastasis from lobular breast carcinoma. Unusual cause of urinoma].

PMID- 7569091
TI  - [Role of low-dose radiotherapy in the multimodal treatment of Kasabach-Merritt
      syndrome].

PMID- 7569089
TI  - [Quantification of pulmonary emphysema with computerized tomography. Comparison
      with various methods].
AB  - Computed Tomography (CT) has been proved to be the most accurate imaging modality
      to diagnose emphysema in vivo. Our study was aimed at comparing different CT
      methods for pulmonary emphysema quantification in patients with severe chronic
      obstructive pulmonary disease (COPD). Forty-six consecutive inpatients affected
      with COPD underwent high resolution CT (HRCT). Three scans were acquired at 3
      preselected anatomic levels at both full inspiration and expiration. Three
      different observers were asked to subjectively evaluate, under blind conditions,
      the extent alone and both the severity and the extent of emphysema on the 6
      scans. HRCT findings were also analyzed quantitatively by measuring the mean CT
      number in Hounsfield Units (HU) and the % of lung area with CT numbers < -900 HU
      (pixel index). Quantitative CT data were compared with reference values obtained
      in 7 normal nonsmokers. The CT visual score of emphysema exhibited medium-high
      interobserver reproducibility with correlation coefficients ranging from 0.80 to
      0.96 and a good correlation with pulmonary function tests, particularly relative
      to the assessment of the extent of emphysema alone as expressed by one observer.
      CT quantification demonstrated an excellent correlation with functional indices
      of expiratory airflow, lung volumes and diffusion coefficients (p < 0.001). The
      expiratory measurements were better than the inspiratory ones while the analysis
      of both CT number and pixel index gave comparable results. Only the CT expiratory
      quantitative data allowed to differentiate the patients affected with COPD from
      the controls. In conclusion, the severity of emphysema as expressed by CT
      correctly reflects the functional impairment of patients with severe
      COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569092
TI  - [Thoracic radiography. Comparison of asymmetric screen-film, technic of
      mechanical homogenization, and conventional technics].
AB  - This study was aimed at comparing three different systems, i.e., asymmetric
      screen-film, mechanical homogenized and conventional techniques, in standing
      frontal and lateral plain radiographs of the chest. Two hundred consecutive
      patients with normal posteroanterior (PA) and lateral films were randomly
      subdivided into 4 groups. Each group was submitted to chest radiographs with a
      different technique: asymmetric screen-film systems (InSight HC and High Light
      GCA), mechanical homogenized (Tau-Gil Homogenized) and conventional high
      kilovoltage techniques. The exposure values for frontal projections ranged 110 kV
      (InSight HC) to 141 kV (Tau-Gil), while for lateral projections they ranged 123
      kV (conventional technique) to 143 kV (Tau-Gil). Statistically significant
      differences were observed between the two asymmetric systems as regards exposure
      values, High Light exhibiting higher mean values in the frontal projection (t
      test p < 0.05). Image quality was studied jointly by 3 experienced chest
      radiologists. The observers were asked to grade, on a 3-point ordinal scale, the
      conspicuity of mediastinal borders, of pulmonary vessels and of selected areas of
      lung parenchyma (i.e., retrocardiac, retrosternal and apical regions), as well as
      overall image quality on the frontal projection. The statistical analysis of
      paired differences was performed with the Mann-Whitney U-test. The asymmetric and
      the mechanical homogenized techniques were much better than the conventional
      technique in depicting tracheobronchial tree, retrocardiac parenchyma, azygos
      esophageal recess and thoracic spine (p < 0.05). The mechanical homogenized
      system provided best overall image quality on frontal films, being superior to
      both InSight HC and conventional techniques, but not to the High Light GCA
      system; only the frontal projection obtained with the homogenized technique was
      compared, no filter being available for the lateral projection. When the two
      asymmetric systems were compared, the High Light system better depicted vascular
      structures on frontal films (p < 0.05), while apical areas were better
      demonstrated with the InSight system, namely with lateral films (p < 0.05).

PMID- 7569093
TI  - [Iopentol in varix radiography. Double blind comparison with iohexol].
AB  - This trial was aimed at comparing the tolerance and the safety of Iopentol, a new
      nonionic monomeric contrast agent, with Iohexol, a reference compound already on
      the market and commonly used in similar trials. Sixty adult patients (41 women
      and 19 men, aged 23 to 76 years, mean age: 51.4 years) referred to our Department
      of Radiology for varicography 24 hours before surgery were examined; the trial
      was designed as a double-blind, parallel two-group comparison of Iopentol 300
      mg/ml and Iohexol 300 mg/ml with 30 patients in each treatment group. No adverse
      reactions were observed in our series of patients. Only slight and not clinically
      significant changes were observed in heart rate and blood pressure values. The
      immunohistochemical parameters were studied for postvaricography
      anatomopathologic complications of the injected veins (A-Actin ML, Vimentin,
      Factor VIII, CD31, CD68, CK, Ulex Europaeus I, Lecitin, Desmin, Laminin) and no
      statistically significant differences were observed between the two groups. The
      histologic specimens showed only venous wall changes, as diagnosed on admission.
      All radiographs were classified as technically adequate and contrastographic
      efficacy was defined as "good" in all patients by two independent radiologists.
      To conclude, our trial on the efficacy and safety of the two nonionic monomeric
      radiographic contrast agents Iopentol and Iohexol proved the two contrast agents
      to be equally effective and well tolerated, which makes Iopentol a good
      alternative to Iohexol in varicography.

PMID- 7569094
TI  - [Phlebography with MR in the study of deep venous thrombosis].
AB  - MR phlebography was recently proposed as a possible alternative to contrast
      venography in the detection of deep venous thrombosis. We focused our work on the
      study of the pelvic veins since it is at this level that contrast venography and
      the other noninvasive techniques, i.e., phlebography, impedance plethysmography
      and US, exhibit their major limitations. Thirty patients underwent MR
      phlebography: 13 of them had a diagnosis of DVT of the pelvic venous district and
      the other 17 had negative results for this condition. All the patients were also
      examined with color-Doppler US at the pelvis and legs. In all the patients
      submitted to MR phlebography, thrombosis site and presence were demonstrated,
      with diagnostic information also on its extent and adhesion to vein wall. To
      conclude, MR phlebography can provide contrast venography-like images in a
      noninvasive way, with high accuracy (100% sensitivity and 90% specificity)
      especially in the pelvic district where the limitations of other techniques are
      more apparent. Larger series of patients must be studied to assess the actual
      role of MR phlebography in the patients with DVT or at high risk for this
      condition.

PMID- 7569095
TI  - [Defecography study of outpouchings of the external wall of the rectum: posterior
      rectocele and ischio-rectal hernia].
AB  - PURPOSE: To report the clinical and defecographic features of posterior rectal
      wall outpouchings, i.e., posterior rectocele and ischiorectal hernia. MATERIALS
      AND METHODS: Sixty-six patients with posterior rectal wall outpouching (61 with
      posterior rectocele and 5 with ischiorectal hernia) were selected among the
      patients examined in the last two years for defecation disturbance. All patients
      underwent physical examination, rectoscopy and videodefecography. RESULTS:
      Posterior rectal wall outpouchings were detected at physical examination in 28
      patients and at rectoscopy in 9 patients. Posterior rectocele, more frequent and
      bigger in men, was usually demonstrated at videodefecography as an outpouching of
      the lower portion of posterior rectal wall: this finding was visible only in the
      dynamic phases in 51 patients while it was seen also at rest in 10 patients. In
      52 patients, posterior rectocele was associated with other abnormalities--i.e.,
      anterior rectocele (64%), puborectal muscle syndrome (38%), descending perineum
      (33%), mucosal prolapse (33%) and intussusception (20%). An ischiorectal hernia,
      defined as a posterolateral ampullar outpouching deeper than 4 cm and already
      visible at rest, was identified in 5 patients. Descending perineum and anterior
      rectocele were the most common associated disorders. CONCLUSIONS: We report the
      clinical and defecographic features of these rectal abnormalities and stress the
      importance of videodefecography in the real-time study of these morphofunctional
      disorders.

PMID- 7569097
TI  - [Transrectal ultrasonography in the study of recurrences in patients surgically
      treated for rectal neoplasms].
AB  - The value of transrectal US is known in the preoperative staging of rectal cancer
      but remains debated in the follow-up of the patients submitted to anterior
      resection or local therapy. The authors report their experience with the
      postoperative follow-up of 80 patients submitted to 125 transrectal US exams to
      study method reliability. The results were 9 true positive, 2 false positive, 113
      true negative and 1 false negative cases, with 90% sensitivity, 98.3% specificity
      and 97.6% accuracy rates. Positive predictive value was 81.8% and negative
      predictive values was 99.1%. Twelve patients were submitted also to MRI which
      correctly diagnosed one false negative result of transrectal US. Twenty-one
      patients were examined also with transrectal Doppler and color-Doppler US: in
      rectal cancer recurrences the peak velocity of hemorrhoid vascular flow was
      higher than in non-recurrent patients. On the basis of our results, transrectal
      US deserves to be included in the postoperative follow-up of the patients
      submitted to anterior resection or to local therapy for rectal cancer. Moreover,
      according to our preliminary findings, Doppler and color-Doppler US can improve
      transrectal US reliability in detecting local recurrences.

PMID- 7569096
TI  - [Diagnostic imaging of intestinal invaginations in the adult. Report of 9 cases].
AB  - Adult intestinal intussusception affects the distal portions of the small bowel
      and the colon in 90% of cases. As a rule, its nature is neoplastic, its clinical
      presentation aspecific and its diagnosis is frequently an occasional finding
      during routine imaging examinations. We report on 9 adult patients with
      intestinal intussusception. All patients were examined with more than one of the
      following imaging modalities: radiologic study of the small bowel, barium enema,
      ultrasonography (US), and Computed Tomography (CT). The first diagnostic
      suspicion of intussusception was correctly made at US in 5 patients and at CT in
      4 patients. At surgery, intussusception sites were the following: jejunum in one
      case, ileum in two cases, ileocolon in two cases and colon in four cases. CT
      correctly detected lesion site in all the patients who underwent it as the first
      diagnostic step, while US missed lesion site in one case. Pathology diagnosed a
      hamartomatous jejunal polyp, a lymphomatous ileal polyp, a lymphomatous polyp of
      the ileocecal valve, four cecocolonic adenocarcinomas and a left colic lipoma.
      Lesion nature was suspected at US in one case of ileal lymphoma, while CT
      suggested the presence of lipoma in one case of ileoileal intussusception. Our
      experience shows that intussusception can be diagnosed not only with conventional
      radiologic modalities, but also with US and CT, which are useful to depict both
      the lesion and its site and extent.

PMID- 7569098
TI  - [Magnetic resonance in the study of inflammatory diseases of the pancreas].
AB  - The role of diagnostic imaging modalities in pancreatic inflammatory diseases is
      to assess gland damage and peripancreatic tissue involvement. The artifacts
      related to breathing and to peristaltic movements can be partially resolved with
      the optimization of acquisition parameters, which allows MRI to be suggested for
      the assessment of pancreatic inflammatory conditions. Sixty-nine patients with
      pancreatic inflammatory diseases (20 acute and 49 chronic pancreatitis cases)
      were examined. MRI was performed with a 0.5-T superconductive magnet and T1- and
      T2-weighted spin-echo (SE) sequences. In 4 of 20 acute pancreatitis patients
      image quality was poor. MRI in acute pancreatitis demonstrated glandular edema,
      intraparenchymal necrosis and the extent of peripancreatic fluid collections; in
      chronic pancreatitis MRI depicted glandular atrophy and Wirsung duct dilatation
      and detected the presence of pseudocysts. Even though its spatial resolution is
      lower than that of CT, MRI can provide useful pieces of information in
      inflammatory diseases of the pancreas, much more so after the introduction of
      Fast SE sequences and of fat-saturation techniques which are likely to make MR
      examinations of the pancreas more widely used.

PMID- 7569099
TI  - [Doppler ultrasonography of the intrarenal arteries before and after radiologic
      treatment in obstructive uropathy].
AB  - Resistive index (RI) calculation on Doppler tracing of intrarenal arterial blood
      flow is a sensitive method for the early diagnosis of obstructive uropathy.
      However, the RI is not specific and can increase in a number of other conditions,
      e.g., old age, circulating endogenic factors or drugs, other nephropathies. The
      authors investigated RI usefulness and accuracy by measuring it both before and
      after the radiologic treatment of acute urinary obstruction in 21 patients, 9 of
      whom had chronic renal failure due to other causes, i.e., hypertension, diabetes
      and chronic pyelonephritis. The clinical conditions of the patients limited the
      feasibility of RI measurements before and after nephrostomy to 66%. In 22 kidneys
      in 17 patients examined before nephrostomy, the RI ranged 0.63 to 0.93 (mean:
      0.80); when the obstruction was unilateral, the RI was always higher than in the
      contralateral kidney. In 25 kidneys in 18 patients examined after nephrostomy,
      the mean RI value was 0.68 (15% lower than before). Taking 0.7 as the cut-off
      value, RI sensitivity in detecting acute urinary obstruction was high (about
      90%), while its specificity was low (about 50%); specificity increased (to about
      80%) when other concomitant causes of increased intrarenal arterial resistance,
      e.g., other vascular or parenchymal nephropathies, were not considered. In some
      cases, the method was also useful in excluding the presence of recurrent
      obstruction after ureteral stent removal. In conclusion, Doppler US values of
      intrarenal arterial perfusion are indicative of acute urinary obstruction when
      they can be compared with those from the contralateral healthy kidney or when
      they can be measured, in the same patient, before and after decompressive
      nephrostomy. In other cases, other nephropathies and some technical limitations
      must be considered.

PMID- 7569101
TI  - [Progressive multifocal leukoencephalopathy in patients with AIDS. Findings with
      computerized tomography and magnetic resonance].
AB  - Progressive Multifocal Leukoencephalopathy (PML) is a subacute demyelinating
      opportunistic infection of the central nervous system which frequently occurs in
      AIDS. CT and MR, together with clinical and virological findings, can suggest a
      correct diagnosis in most cases, thus avoiding stereotactic biopsy which is too
      invasive considering the lack of therapy and the poor prognosis of this disease.
      In this study we reviewed the CT and MR findings of 16 proved AIDS-related PML
      cases. PML lesions appeared as hypodense on CT, hypointense on T1w, hyperintense
      on PDw and T2w MR images. CT was less sensitive than T2w MR images and
      underestimated the number of lesions and/or disease extent. On the basis of our
      findings during the progression of the lesions we observed two different patterns
      of PML presentation and evolution i.e., "single" and "multifocal". Single lesions
      generally involve subcortical white matter (arcuate fibers) of parietal lobe and
      spread to the contralateral hemisphere across the corpus callosum; multiple
      "patchy" lesions can be localized variably in the cerebral hemispheres and also
      in the brainstem and cerebellar hemispheres.

PMID- 7569100
TI  - [Assessment of primary renal lymphoma with computerized tomography].
AB  - Renal involvement during lymphoma can be extrinsic, i.e., renal compression or
      displacement due to lymph node masses, or intrinsic, i.e., parenchymal
      involvement secondary to blood or lymphatic spread, or primary, as initial
      neoplastic site. Primary renal lymphoma is very rare (3% of all renal lymphomas)
      for the absence of lymphatic tissue in the kidney. The disease might be due to
      parapyelic lymph nodes or to blood spreading from an unknown site. In our study
      we reviewed the CT findings of five cases of primary non-Hodgkin's renal lymphoma
      with surgical or histologic confirmation. Renal alterations due to lymphomatous
      involvement were classified according to macroscopic pathologic findings: type I
      (single nodular disease, 2 patients), type II (multinodular disease, 1 patient),
      and type III (infiltrating disease with retroperitoneal involvement, 2 patients).
      In the two patients with single nodular involvement (type I), CT showed a solid,
      hypodense and clear-cut nodule. In the only patient with multinodular disease
      (type II), renal tissue was replaced by multiple hypodense nodular masses, which
      were partially confluent. In the two infiltrating forms with retroperitoneal
      involvement (type III), renal structure was diffusely disorganized, with
      thickening of soft tissues and perirenal fasciae, peripyelic infiltration and, in
      one case, urinary tract obstruction. To conclude, CT always allowed the accurate
      assessment of the presence, site and size of renal lesions and of perirenal and
      urinary involvement. However, CT findings were completely aspecific, not allowing
      an unquestionable differential diagnosis with other conditions, e.g.,
      hypernephroma, transitional cell carcinoma, metastatic lesions or chronic
      inflammations. Therefore, a biopsy specimen is necessary to make an
      unquestionable diagnosis.

PMID- 7569103
TI  - [CT-guided percutaneous treatment of osteoid osteoma].
AB  - CT was used to localize and guide the percutaneous ablation of osteoid osteomas
      in 11 patients whose age ranged 5 to 63 years. The treatment was performed
      directly in the CT room ensuring maximum asepsis. General anesthesia was used in
      children and in vertebral and sacroiliac localizations, while the peripheral
      block was used in peripheral localizations. In the latter cases, an ischemic band
      was used to reduce bleeding. A dedicated drill resection system guided by a
      Kirschner guide wire was used for removal. The treatment was curative in the
      short period in all the patients, with complete symptom remission. Only one
      patient required retreatment after 6 months. In our series of patients no major
      complications, e.g., bleeding or infections, were observed. In 8 cases the
      resection yielded enough material for histology. To conclude, this technique can
      be considered a valuable alternative to surgery in the treatment of osteoid
      osteomas.

PMID- 7569102
TI  - [The use of computed tomography guided needle biopsy in thoracic lesions in
      childhood].
AB  - Percutaneous fine-needle aspiration biopsy (FNAB) is widely used in adult but not
      in pediatric patients, probably because young patients cooperate little. Twenty
      six CT-guided FNABs were performed in children aged 40 days to 15 years (mean:
      11.6 years) from January through December, 1993. The lesions were found in
      anterior mediastinum (17 cases), posterior mediastinum (5 cases) and lung (4
      cases). Some specimens were fixed for cytology and some were cultured. Twenty
      five of 26 biopsies (96.1%) provided adequate material for the cytologic assay,
      while in one case the result was poor because of much necrotic material.
      Cytologic findings were compared with postoperative biopsy results in 9 cases and
      confirmed by follow-up in 17 non-surgical lesions.

PMID- 7569106
TI  - Pancreas transplantation.
AB  - Vascularized pancreas transplantation has assumed an increasing role in the
      treatment of diabetes mellitus. Through 1994, over 6000 pancreas transplants had
      been performed worldwide, with over 80% being combined pancreas-kidney
      transplants. Overall 1-year patient survival exceeds 90% and graft survival
      (complete insulin independence) exceeds 70%. Although successful pancreas
      transplantation achieves euglycemia and complete insulin independence, this
      occurs at the expense of hyperinsulinemia and chronic immunosuppression. The net
      effect of these changes on diabetic complications in the long term remains to be
      determined. In the short term, improvement in the quality of life and possible
      prevention of further morbidity associated with diabetes makes pancreas
      transplantation an important therapeutic option, particularly when combined with
      a kidney transplant, in appropriately selected diabetic patients.

PMID- 7569104
TI  - [Isoflurane in angiography with magnetic resonance].
AB  - The authors investigated if the use of vasodilating drugs could increase Magnetic
      Resonance angiography (MRA) capabilities in demonstrating intracranial vessels.
      Twenty patients (mean age: 10 years) were examined with MRA: a vasodilating drug
      (isoflurane) was administered to 10 of them and 10 matched-pair subjects were
      selected as controls and submitted to MRA without receiving any drug known to
      increase cerebral blood flow. MRA was performed with a 1.5-T superconductive
      magnet; FISP 3D sequences were used in all cases. A multiple choice card was used
      by a reader reporting the following diagnostic information for the different
      segments of the intracranial vessels: 1) hyperintense and homogeneous vessel with
      high signal-to-noise (S/N) ratio; 2) hyperintense and heterogeneous vessel with
      high S/N ratio; 3) hyperintense vessel with low S/N ratio; 4) poor vessels
      depiction. Small vessels (ophthalmic arteries, A3, M3, M4, anterior communicating
      arteries and P2 segments) were better demonstrated with isoflurane than with
      conventional MRA. The results were compared with the Mann-Withney test:
      isoflurane MRA allowed good vessel depiction in 127 cases, versus 83 of
      conventional MRA; the difference was statistically significant. To conclude, the
      use of vasodilating drugs represents a new research field in MRA of the
      intracranial vessels.

PMID- 7569105
TI  - [Combined chemo-radiotherapy in non-operable cervico-facial neoplasms. Final
      results of an experience with non-selected patients].
AB  - The management of advanced inoperable head and neck cancer is often based on a
      combined chemo-radiotherapy approach. No definitive conclusions on the
      effectiveness of this combination can be drawn from clinical trials because these
      neoplasms are heterogeneous and treatment schedules vary. Many scientific trials
      test highly toxic combinations, whereas not only good results but also low
      toxicity are mandatory in the current practice. We report the results obtained in
      90 consecutive patients affected with inoperable head and neck cancers in stages
      III-IV, or relapsed after surgery. Chemotherapy consisted of a cis
      platinum/bleomycin induction phase, followed by weekly administrations of cis
      platinum simultaneous with conventional irradiation. The objective remission
      rates, achieved at the end of the induction chemotherapy and the simultaneous
      chemo-radiotherapy phases, were respectively 55.5% and 84.5%. The tumor
      disappeared in 39% of cases, by the end of the whole treatment. With the Kaplan
      Meier method, 3-year overall, progression-free and relapse-free survival rates
      were 21.20%, 22.25% and 38.75%, respectively. The overall survival rate,
      calculated with the "log-rank" test according to the stage and the site of the
      primary tumor, exhibited no significant differences. In contrast, significant
      differences (p < 0.05) were demonstrated, according to treatment intent (curative
      radical: 26%, vs palliative: 0%) and to the achievement of an objective response
      at the end of induction chemotherapy--i.e., 48% 3-year survival rate, vs 7% in
      chemotherapy resistant cancer patients. When limiting the analysis to 72
      radically irradiated patients, however, the achievement of CR after induction
      chemotherapy lost its prognostic value. Toxicity was not substantially higher
      than with conventional irradiation. Our results are in agreement with literature
      data on this subject which, regarding survival, fail to prove such integrated
      treatments as ours better than irradiation alone. In contrast, the preliminary
      combination of chemotherapy and irradiation is clearly better for the patients
      waiting to receive radiation therapy, because tumor volume and related symptoms
      markedly decrease after induction chemotherapy. Currently the best survival rates
      (about 50% at 3 years) with chemo-radiotherapy are obtained, in this kind of
      cancer, by combining cis-platinum and continuous-infusion 5-fluorouracil,
      simultaneous with irradiation. However, frequent and severe toxicity is reported.
      Should such a modality be adopted in the current practice, patients should be
      selected according to their medical conditions.

PMID- 7569107
TI  - Role of the kidney in the production of a low molecular weight growth factor (MW
      < 1000 Da): experimental study in the pig.
AB  - Small peptide molecules known as low molecular weight growth factor (LMW-GF) have
      been identified in human serum. They enhance the effect of IGF-1 (insulin-like
      growth factor) on proteoglycan synthesis. In the present work we investigated the
      role played by the kidney in the production of LMW-GF, using the pig as an
      experimental model. Six pigs underwent bilateral nephrectomy followed 24 h later
      by orthotopic autotransplantation of the kidney. Renal and liver functions were
      evaluated by measurement of serum creatinine, urea, electrolytes, amino
      transferases (ASAT, ALAT), proteins, and bilirubin. LMW-GF was measured by
      bioassay using 11-day-old pelvic chick embryo cartilages. We observed that LMW-GF
      quickly disappeared from pig serum after nephrectomy and only reappeared when
      transplantation was successful. Reappearance of LMW-GF can precede improvement of
      renal function evaluated by plasma creatinine levels. These data appear to
      demonstrate that the kidney is involved in LMW-GF production.

PMID- 7569109
TI  - Angiotensin I converting enzyme in glycerol-induced acute renal failure in rats.
AB  - Angiotensin I converting enzyme (ACE) activity was measured in serum, urine, and
      tissues of rats with acute renal failure (ARF) induced by glycerol. Glycerol
      injected rats were subdivided in three groups according to the urinary volume:
      oliguric, nonoliguric, and polyuric. The damage to the proximal tubule was
      evident by (a) the histological analysis at light and electron microscopy level,
      (b) the augmented urinary excretion of the enzymes dipeptidyl aminopeptidase IV
      and N-acetyl-beta-D-glucosaminidase, and (c) the low molecular weight proteinuria
      pattern. On the other hand, the appearance of the glomeruli at the
      ultrastructural level was normal. These data suggest that the increased urinary
      excretion of enzymes and proteins in these rats is a consequence of the tubular
      injury. ARF was markedly higher in the oliguric rats. Urine ACE activity
      increased in the rats of the three groups, but statistical significance was
      reached only in the oliguric rats. Serum ACE activity increased in the oliguric
      rats and tissue ACE activity did not change. It is concluded that the high
      urinary ACE in glycerol-treated rats is associated with the damage to the kidney
      tubules. These data support the contention that urinary ACE may be another marker
      of injury to the proximal tubule.

PMID- 7569110
TI  - Angiotensin I converting enzyme activity in uranyl nitrate induced acute renal
      failure in rats.
AB  - Angiotensin I converting enzyme (ACE) was measured in urine, serum, and tissues
      from rats with acute renal failure (ARF) induced by a single subcutaneous
      injection (15 mg/kg BW) of uranyl nitrate (UN). Urine was collected daily until
      day 5, when rats were sacrificed by decapitation for the obtention of blood serum
      and tissues. Other groups of rats were sacrificed on days 1 and 2. These rats
      showed proteinuria and polyuria. The damage to the kidney proximal tubule was
      shown by (a) histological analysis at light and electron microscopy levels on
      days 1, 2, and 5, (b) the increase in urinary excretion of dipeptidyl
      aminopeptidase IV and N-acetyl-beta-D-glucosaminidase on days 1-5, and (c) the
      low molecular weight proteinuria pattern on day 1. In addition, the histological
      analysis at the ultrastructural level showed normal glomeruli appearance on days
      1 and 2, but structural alterations on day 5. These data suggest that the
      increased urinary excretion of enzymes and proteins is a consequence of the
      tubular injury on days 1 and 2, and of tubular and glomerular injury on day 5.
      ACE activity increased in urine on days 1-5 and in serum on day 5. Tissue ACE
      activity increased in lung, small intestine, and adrenal glands; and remained
      unchanged in testis, aorta, brain, kidney, heart, and liver. Our data suggest
      that: (a) the increase in serum ACE may be secondary to the changes in tissue ACE
      activity, and (b) the urine ACE increase may be due to the kidney proximal tubule
      damage. This work supports the contention that an increase in urine ACE may be an
      indicator of injury to the proximal tubule.

PMID- 7569108
TI  - Renal changes of streptozotocin-induced diabetic rats fed a low-zinc diet.
AB  - The changes in kidneys of streptozotocin (STZ)-induced diabetic rats fed a low
      zinc (LZ) diet were observed. Calcium deposits were detected in the LZ-diabetic
      groups from the 2nd to the 8th week. The deposits were mainly detected in the
      corticomedullary junction, and found in the tubular lumina and epithelial
      cytoplasm and interstitium. Tubular morphological changes, including luminary
      distension, epithelial flattening, and paleness of cytoplasm and nuclei, were
      observed near the calcium deposits in the LZ-diabetic group over the 2nd week.
      Moreover, at the 8th week, wedge-shaped vasogenic lesions were found on the
      surface of the renal cortex in the LZ-diabetic group. No changes were detected in
      the control for the LZ or in the diabetic group fed a standard (SC) diet. When
      STZ was administered, plasma glucose level in groups fed LZ or SC diet increased
      in the 1st week, and over the 2nd week, glucose level was maintained at more than
      400 mg/dL. Glucose level of the LZ-diabetic group did not differ from that of the
      SC-diabetic group. However, urinary N-acetyl-beta-D-glucosaminidase activity of
      the LZ-diabetic group at the 8th week was significantly higher than that of the
      SC-diabetic group. These findings suggested that low-zinc diet hastens renal
      damages in diabetic rats.

PMID- 7569111
TI  - Nitric oxide synthase inhibition and acute renal ischemia: effect on systemic
      hemodynamics and mortality.
AB  - This study was designed to examine if acute systemic blockade of nitric oxide
      (NO) production by inhibition of nitric oxide synthase (NOS) with N-omega-nitro-L
      arginine methyl ester (L-NAME) would worsen the severity of ischemic acute renal
      failure (ARF). Initially three groups of rats, were studied: 45 min of bilateral
      renal ischemia (I) alone, Group I; L-NAME (L; 10 mg/kg BW, i.v.) alone, Group L;
      and L-NAME administered 15 min before renal ischemia, Group L+I. We observed,
      however, a 60% mortality in Group I+L during the first 4 h of reflow. Captopril,
      administered acutely 15 min before L-NAME in an attempt to offset any detrimental
      effects of increased angiotensin II generation in response to renal ischemia,
      failed to obviate the mortality because 67% of rats in this group (Group C+L+I)
      also died. Therefore, additional studies were performed in rats instrumented for
      cardiovascular studies to evaluate the acute hemodynamic responses during the
      first 90 min of reperfusion following renal ischemia in rats pretreated with L
      NAME. As expected, L-NAME injection was accompanied by a 25-30 mm Hg increase in
      mean systemic arterial pressure (SAP) (p < 0.05), a bradycardia (p < 0.02), and a
      decrease in cardiac output (CO) (p < 0.02). The increase in SAP was due
      exclusively to an increase in systemic vascular resistance (SVR) (p < 0.01).
      Ischemia and reflow in the L-NAME-treated rats were attended by a progressive
      increase in SVR and a progressive decrease in CO such that by the end of 45 min
      of reperfusion SVR had increased 10-fold and CO had decreased to one third of its
      initial rate (both p < 0.02). Pulmonary artery pressure (PAP) increased promptly
      following L-NAME injection. Total pulmonary resistance (PRT) increased
      significantly by the end of reperfusion. L-NAME in combination with renal
      ischemia and reflow induces a large increase in both SVR and PRT, and is
      accompanied by a 70% reduction in CO and substantial mortality.

PMID- 7569115
TI  - IgA nephropathy in renal allografts: increased frequency in Native American
      patients.
AB  - We investigated the frequency of IgA nephropathy in transplanted kidneys in 2
      ethnic groups in New Mexico (USA). A total of 80 renal graft biopsies were
      obtained from 66 patients when clinically indicated for the differential
      diagnosis of graft dysfunction. Glomerulonephritis was present in 16 patients, in
      biopsies obtained after the first posttransplantation month. The frequency of
      IgAN in allografts was not the same in Native Americans and in Caucasians:
      Nondonor IgAN was observed in 4/18 biopsies from Native American patients (22.2%)
      but only in 4/48 biopsies from Caucasians (8.3%) (p < 0.01). This study
      demonstrates that in New Mexico the frequency of IgAN in transplanted kidneys in
      Native American patients is 2.7 times higher than in Caucasian graft recipients.

PMID- 7569114
TI  - Progressive ischemic gangrene in dialysis patients: a clinicopathological
      correlation.
AB  - The syndrome of progressive ischemic gangrene (PIG) of the extremities was
      examined over 3.5 years in patients undergoing maintenance dialysis (MD) in
      Kuwait and was compared to that in a similar age group (> 40 years) in the
      general population. The incidence of PIG in MD patients was 15.4/1000 person
      years of observation (PYO) versus 0.086/1000 PYO in the general population.
      Patients with diabetes mellitus were found to be at particular risk. PIG
      developed in 41.4/1000 PYO of diabetic patients who received MD, compared to
      7.1/1000 in nondiabetic patients on MD and 0.14/1000 in diabetics without renal
      disease. The clinical, biochemical, radiological, and histological findings in
      the 8 patients who developed PIG while on maintenance dialysis (MD) are
      presented. Two patients had severe hyperparathyroidism and their histological
      findings were consistent with systemic calciphylaxis. Histological examination,
      in the remaining patients, showed severe calcified atherosclerosis. Intimal
      hypertrophy was common especially in patients with long duration on dialysis. The
      three lesions produced a variable degree of luminal narrowing and were associated
      with arterial thrombosis. None of the patients showed evidence of iron deposition
      even in those with systemic calciphylaxis and excessive iron stores. Our study
      indicated a high incidence of PIG in patients undergoing MD, especially in those
      with diabetes mellitus. These findings constitute a cogent argument in favor of
      early parathyroidectomy in selected cases and concern with long-term consequences
      of atherosclerosis in this patient population.

PMID- 7569113
TI  - Effect of extracellular calcium on survival of human proximal tubular cells
      exposed to hypoxia.
AB  - Removal of extracellular calcium has been demonstrated to improve membrane
      integrity of rodent myocytes, astrocytes, and renal tubular cells injured by
      hypoxia. In this study, the effect of extracellular calcium on long-term survival
      of cultured human proximal tubular epithelial cells (PTEC) subjected to hypoxia
      was evaluated. In addition, the effect of extracellular calcium on release of
      arachidonic acid metabolites (AAM) was assessed during and after hypoxia. To
      induce hypoxic injury, PTEC were incubated in an anaerobic chamber in glucose
      free buffer (combined oxygen/glucose deprivation, COGD). Long-term survival was
      assessed by measuring lactate dehydrogenase (LDH) efflux during COGD and after an
      additional 24-h "recovery" period (in routine culture medium in 95% air/5% CO2).
      To determine if extracellular calcium influenced AAM release from membrane
      phospholipids, cells were preincubated with [3H]arachidonic acid and the release
      of AAM was measured during COGD and recovery. With this model system, PTEC
      exhibited minimal LDH efflux during < or = 12 h COGD, but LDH efflux increased to
      73.9 +/- 4.7% by 24 h COGD. With 12-18 h of COGD, the extent of LDH efflux was
      greater during recovery than during COGD, indicating that, for human PTEC, the
      extent of membrane damage does not become fully evident by LDH efflux for hours
      after hypoxia. PTEC exposed to 24 h of COGD in the absence of extracellular
      calcium exhibited strikingly less LDH efflux during COGD than cells incubated in
      the presence of extracellular calcium, suggesting that extracellular calcium
      contributes to membrane damage during COGD. However, upon reexposure of PTEC to
      extracellular calcium, LDH efflux rapidly increased to control levels.
      Furthermore, despite allowing cells to recover in oxygen or oxygen and glucose
      before exposure to calcium-containing medium, a rapid increase in LDH efflux
      could not be avoided. These results suggest that COGD induces an irreversible
      injury that ultimately leads to loss of membrane integrity whether or not
      extracellular calcium is present; however, extracellular calcium accelerates the
      loss of membrane integrity caused by hypoxia. Extracellular calcium did not alter
      AAM release, indicating that the effect of extracellular calcium on membrane
      damage (as indicated by LDH efflux) was not mediated by an increased activity of
      phospholipases (such as phospholipase A2) that are involved in the release of
      AAM.

PMID- 7569116
TI  - Interleukin-6 and interleukin-8 extraction during continuous venovenous
      hemodiafiltration in septic acute renal failure.
AB  - OBJECTIVES: To determine whether continuous venovenous hemodialfiltration (CVVHD)
      is associated with the extraction of interleukin-6 (IL-6) and interleukin-8 (IL
      8) from the circulation of critically ill patients with septic acute renal
      failure. To quantitate their clearance and assess any possible effect of CVVHD on
      these cytokines' serum concentrations. DESIGN: Prospective controlled study of IL
      6 and IL-8 removal by CVVHD in patients with septic acute renal failure. SETTING:
      Intensive care unit of a tertiary institution. PATIENTS: Ten critically ill
      patients with sepsis, acute renal failure, and multiorgan failure. A control
      group of five patients experiencing an acute illness while undergoing chronic
      hemodialysis. INTERVENTIONS: Collection of blood samples before CVVHD.
      Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 h
      of treatment. IL-8 concentrations were measured in blood and ultradiafiltrate.
      Their clearances and daily extractions were calculated. MEASUREMENTS AND MAIN
      RESULTS: IL-6 and IL-8 were detected in the blood of all patients with septic
      acute renal failure prior to CVVHD. The median IL-6 blood level was 103 pg/mL
      (range: 19 to 900) and the median IL-8 blood level was 200 (range: 32 to 2925).
      Both cytokines were cleared by the hemofilter during CVVHD. The median hemofilter
      clearance of IL-6 were 1.99 L/day (range: 0 to 8.5) and the median clearance of
      IL-8 was 3.95 L/day (range: 0.31 to 42.8). These blood levels and clearances
      resulted in median daily extraction rates of 194 ng of IL-6 (range: 0 to 9031)
      and of 915 ng of IL-8 (range 47.5 to 3562). Control patients had negligible
      amounts of either IL-6 or IL-8 in their ultrafiltrate. The rate of extraction for
      IL-6 correlated with its blood levels (p < 0.0001). This was not true for IL-8. A
      correlation between IL-6 levels and the patients' white cell counts was found
      after 24 h of hemofiltration. CONCLUSIONS: CVVHD is associated with the
      extraction of IL-6 and IL-8 from the circulation of patients with septic
      multiorgan and renal failure. The biological significance of such extraction is
      undetermined, but such cytokine removal highlights the complexity of the effect
      of continuous hemofiltration on the soluble mediators of inflammation activated
      during human sepsis.

PMID- 7569117
TI  - The clinical and biochemical features of acute renal failure due to
      rhabdomyolysis.
AB  - Rhabdomyolysis caused 28 out of 903 (3.1%) of cases of severe acute renal failure
      (ARF) treated at Leeds General Infirmary over a 14-year period (1980-1993). The
      commonest cause of rhabdomyolysis was muscle compression, usually due to drug- or
      alcohol-induced coma. Other causes included fits, infection, acute limb ischemia,
      trauma, and heat stroke. Prognosis was relatively good, with a 78.6% survival
      rate and recovery of renal function to normal in all survivors who were followed
      up. The creatinine/urea ratio was higher in ARF due to rhabdomyolysis than in an
      unselected group of patients with other causes of ARF but not when the comparison
      was with sex- and age-matched controls with ARF. This suggests that this
      previously described feature of rhabdomyolysis simply reflects the increased
      muscle mass of a younger group of patients, rather than a specific effect of
      muscle damage. Clinical features of muscle damage were often absent and so the
      possibility of rhabdomyolysis should be considered in appropriate settings if the
      diagnosis is to be made early enough to administer treatment that may prevent ARF
      and the consequences of the compartment syndrome.

PMID- 7569118
TI  - Rhabdomyolysis and acute renal failure during high-dose haloperidol therapy.
AB  - Severe adverse reactions to neuroleptic medications are not uncommon and include
      the neuroleptic malignant syndrome, rhabdomyolysis, and acute renal failure. The
      neuroleptic malignant syndrome consists of hyperthermia, diaphoresis,
      tachycardia, tachypnea, abnormal blood pressure, alteration of consciousness, and
      extrapyramidal rigidity. Rhabdomyolysis--which might be due to hyperthermia,
      muscle rigidity, and/or metabolic changes in skeletal muscle function--results in
      acute renal failure. We report a patient with rhabdomyolysis and acute renal
      failure that developed after large doses of haloperidol were given, but without
      muscle rigidity or hyperthermia. This patient's presentation illustrates that
      high-dose haloperidol therapy might cause rhabdomyolysis and acute renal failure
      without significant rigidity or hyperthermia.

PMID- 7569119
TI  - Increased glomerular nitric oxide synthesis in ischemic acute renal failure in
      the rat.

PMID- 7569121
TI  - Radiologic history exhibit. 1934: fateful year in the history of African
      Americans in radiology.
AB  - The year 1934, just over a third of the way into the first century of the x ray
      and of the NMA, reflected both successes and difficulties for the minority
      radiologist. African-Americans constituted disproportionately small numbers
      within the radiologic community (Fig 9), and few of them were on the AMA's
      approved list. Membership in major radiologic societies was lacking; many were
      excluded from applying for the new American Board of Radiology examination. On
      the other hand, the major radiology journals began to publish articles by African
      American authors, a select few radiologists were on the AMA specialist list, and
      the first steps to board certification were appearing.

PMID- 7569122
TI  - General case of the day. Enteropathic arthropathy secondary to Crohn disease.

PMID- 7569112
TI  - Induction of heat-shock proteins HSP73 and HSP90 in rat kidneys after ischemia.
AB  - We examined rat kidneys for serial expressions of two major heat-shock proteins
      (HSPs), HSP73 and HSP90, after 60 min of unilateral renal ischemia up to day 28.
      Immunohistochemical studies showed that HSP73 and HSP90 were rapidly induced in
      the cytoplasm of injured epithelial cells of the S3 segment of proximal tubules
      and were again induced in the cytoplasm of regenerative cells in this segment
      from day 3. In epithelial cells of the Henle's loops, HSP90 was also induced in
      the cytoplasm of both injured and regenerative cells, but HSP73 was not induced
      in this portion. Furthermore, a transient accumulation of HSP73 into the nucleus
      was observed in epithelial cells of papillary collecting ducts shortly after
      ischemia. Serial immunoblot analysis of isotonic buffer extractable fractions
      from ischemic kidneys revealed the induction of both HSP73 and HSP90 in the
      degenerative and regenerative phases: the maximal inductions in the two phases
      were at 3-6 and on days 5-7, respectively. These results demonstrate that HSP73
      and HSP90 are induced in injured tubular epithelial cells with a regional
      heterogeneity during the degenerative and regenerative phases after renal
      ischemia and suggest that these HSPs are involved in the process of postischemic
      cellular recovery.

PMID- 7569123
TI  - US case of the day. Retroperitoneal fibrosis with perirenal involvement.

PMID- 7569120
TI  - Three-dimensional spiral CT during arterial portography: comparison of three
      rendering techniques.
AB  - The three most common techniques for three-dimensional reconstruction are surface
      rendering, maximum-intensity projection (MIP), and volume rendering. Surface
      rendering algorithms model objects as collections of geometric primitives that
      are displayed with surface shading. The MIP algorithm renders an image by
      selecting the voxel with the maximum intensity signal along a line extended from
      the viewer's eye through the data volume. Volume-rendering algorithms sum the
      weighted contributions of all voxels along the line. Each technique has
      advantages and shortcomings that must be considered during selection of one for a
      specific clinical problem and during interpretation of the resulting images. With
      surface rendering, sharp-edged, clear three-dimensional reconstruction can be
      completed on modest computer systems; however, overlapping structures cannot be
      visualized and artifacts are a problem. MIP is computationally a fast technique,
      but it does not allow depiction of overlapping structures, and its images are
      three-dimensionally ambiguous unless depth cues are provided. Both surface
      rendering and MIP use less than 10% of the image data. In contrast, volume
      rendering uses nearly all of the data, allows demonstration of overlapping
      structures, and engenders few artifacts, but it requires substantially more
      computer power than the other techniques.

PMID- 7569126
TI  - The power of words.

PMID- 7569125
TI  - Endoscopic US of the gastrointestinal tract with endoscopic, radiographic, and
      pathologic correlation.
AB  - Endoscopic ultrasonography (US) makes it possible to evaluate the layers of the
      wall of the gastrointestinal tract, as well as surrounding structures. The
      authors have used endoscopic US to evaluate the gastrointestinal tract in 160
      patients. In the esophagus, endoscopic US is useful in staging esophageal
      carcinoma, planning radiation therapy ports, and locating and characterizing
      esophageal masses. Endoscopic US of the esophagus is also used to identify
      varices and evaluate the results of therapy. Applications of endoscopic US in the
      stomach include staging of gastric carcinoma, localization and characterization
      of nonmucosal gastric masses, detection and evaluation of gastric varices, and
      evaluation of gastric lymphoma. In the pancreas, endoscopic US is used for
      detecting pancreatic masses; staging pancreatic, distal common bile duct, and
      ampullary carcinoma; and evaluation biliary tract obstruction. Applications of
      endoscopic US in the rectum include localization and characterization of
      nonmucosal lesions and local staging of rectal carcinoma.

PMID- 7569128
TI  - Hepatic arterial anatomy: demonstration of normal supply and vascular variants
      with three-dimensional CT angiography.
AB  - Three-dimensional (3D) helical computed tomographic (CT) angiography is a
      promising method of determining vascular anatomy. This technique is useful in
      delineating the arterial anatomy of the liver, demonstrating the normal anatomy
      and vascular variants in a highly visual fashion. The "typical" hepatic arterial
      anatomy occurs in only 55% of the population, and numerous variants exist; the
      standard classification system for hepatic arterial anatomy includes 10
      variations. After helical scanning, postprocessing with reconstruction algorithms
      such as shaded surface display and maximum-intensity projection provides highly
      graphic, easily understandable views of vascular anatomy. The 3D CT angiograms,
      with their global view of the anatomy and inherent advantage of volumetric
      rotation of the vascular system, are useful to surgeons and others with limited
      experience in interpreting axial anatomy. Determination of hepatic arterial
      anatomy with 3D CT angiography has already been shown to be clinically useful in
      patients being evaluated for liver transplantation.

PMID- 7569124
TI  - Pediatric case of the day. Infected fourth branchial pouch sinus with an
      extensive complicating cervical and mediastinal abscess and left-sided empyema.

PMID- 7569127
TI  - Anatomic CT demonstration of the peritoneal spaces, ligaments, and mesenteries:
      normal and pathologic processes.
AB  - Computed tomography (CT) has become increasingly useful in the detection of
      intraabdominal disease. Owing to the widespread use of CT, it is essential that
      radiologists have a thorough understanding of the peritoneal spaces and the
      ligaments and mesenteries that form their boundaries. The majority of ligaments
      and mesenteries in the abdomen are formed from remnants of the ventral and dorsal
      mesenteries, which suspend the primitive gut. Unlike the abdominal ligaments, the
      pelvic ligaments are mainly formed by reflections of peritoneum over the pelvic
      organs or structures. The mesenteries and ligaments form the boundaries of the
      peritoneal spaces; this knowledge aids in localizing fluid collections, allowing
      the differential diagnosis to be narrowed. The ability to localize fluid
      collections accurately is also important if percutaneous or surgical drainage is
      to be performed. In addition, neoplasms can be more accurately staged when the
      pathway of spread through adjacent ligaments and mesenteries is understood.

PMID- 7569130
TI  - Trigeminal neuropathy: evaluation with MR imaging.
AB  - Neuropathy of the trigeminal nerve can involve its full course, from its nuclei
      in the brain stem to its peripheral branches. The nerve can be divided into four
      segments--brain stem, cistern, the Meckel cave and cavernous sinus, and
      extracranial--and consideration of the pathologic entities by these locations
      simplifies the differential diagnosis. Multiple sclerosis, infarct, and glioma
      are the most common abnormalities in the brain stem leading to trigeminal
      neuropathy. The most common cisternal cause is neurovascular compression,
      followed by acoustic and trigeminal schwannomas, meningiomas, epidermoid cysts,
      lipomas, and metastases. Trigeminal neuropathy arising from the Meckel cave and
      cavernous sinus is frequently due to meningiomas, trigeminal schwannomas,
      epidermoid cysts, metastases, pituitary adenomas, and aneurysms. Malignant
      tumors, which may demonstrate perineural tumor spread, are the most common
      extracranial cause. Because the clinical findings do not permit accurate lesion
      localization, magnetic resonance imaging must be used to visualize the entire
      course of the fifth cranial nerve. The standard study should include T2-weighted
      images of the whole brain and high-resolution axial and coronal T1-weighted
      images of the skull base obtained with and without contrast material enhancement.

PMID- 7569131
TI  - Staging of prostate cancer with endorectal MR imaging: lessons from a learning
      curve.
AB  - Endorectal magnetic resonance (MR) imaging is the most accurate noninvasive
      method of staging prostate cancer. However, inexperienced radiologists may lack
      the necessary technical and interpretative skills to use this technique, and both
      radiologists and referring urologists may become frustrated with this method
      because of its inaccuracy compared with analysis of the radical prostatectomy
      specimen. Meticulous pathologic correlation is necessary to evaluate endorectal
      MR imaging findings. The authors compare their initial experience using
      endorectal MR imaging for staging prostate cancer (25 cases) with their later
      experience (25 cases) to highlight the various diagnostic pitfalls and "pearls"
      one may encounter when using endorectal MR imaging. Knowledge of the pathways of
      tumor spread inside and outside the gland may be helpful in interpreting
      endorectal MR images. The authors achieved a substantial improvement in the
      overall staging accuracy of endorectal MR imaging by careful pathologic
      correlation and by considering the anatomic features of prostate cancer.

PMID- 7569129
TI  - MR angiography of congenital heart disease in adults.
AB  - Magnetic resonance (MR) angiographic techniques are useful in evaluation of adult
      patients with congenital heart disease (CHD). The available techniques include
      cine, breath-hold ungated, and segmented k-space time-of-flight MR angiography.
      Three-dimensional (3D) image reconstruction with maximum-intensity projection can
      be used with all of these techniques to demonstrate great vessel anomalies
      associated with CHD. Selective presaturation MR angiography can be used to detect
      intracardiac shunts. MR angiography allows clarification of difficult diagnostic
      points that are not fully demonstrated with other imaging techniques, such as
      cardiac catheterization and angiocardiography, echocardiography, nuclear medicine
      studies, and conventional spin-echo MR imaging. In many patients with CHD in
      adulthood, the use of appropriate MR angiographic techniques may allow definitive
      diagnosis and preclude the need for cardiac catheterization. The wide field of
      view, sensitivity to shunts, and rapid 3D imaging capability of MR angiography
      make it a valuable method of evaluating CHD in adults.

PMID- 7569132
TI  - Color Doppler US of renovascular disease in native kidneys.
AB  - One hundred eighty-seven native kidneys in 96 patients were examined with color
      Doppler ultrasound (US) to (a) determine the color Doppler US characteristics of
      renovascular disorders and (b) assess the value of color Doppler US in detection
      of such disorders. Correlative angiography or computed tomography was performed
      in 94 patients. The following renovascular disorders were found: renal artery
      (RA) stenosis (40 cases), RA thrombosis (13 cases), RA aneurysm (four cases),
      renal vein thrombosis (three cases), arteriovenous fistula (three cases),
      peripheral infarction (one case of bilateral infarcts), and distal occlusive
      disease (three cases). One case of aortal coarctation was also found. Color
      Doppler US failed to demonstrate the proximal main RA in 25% of cases (among 193
      RAs total including supernumerary RAs). The sensitivity and specificity of color
      Doppler US for the detection of RA stenosis or thrombosis were 89% and 99%,
      respectively. Color Doppler US thus appears to be effective in the diagnosis of
      renovascular disease in native kidneys.

PMID- 7569133
TI  - Normal and abnormal vascular structures that simulate neoplasms on chest
      radiographs: clues to the diagnosis.
AB  - Despite increased use of and reliance on cross-sectional imaging techniques in
      the thorax, conventional chest radiography remains the most commonly performed
      imaging examination. However, conventional radiographic appearances of normal and
      abnormal vascular structures can be misinterpreted as representing neoplasms or
      soft-tissue masses and lead to inappropriate diagnostic procedures. Vascular
      structures that can simulate neoplasms include normal structures such as the
      subclavian artery and left brachiocephalic, azygos, and pulmonary veins and
      abnormal structures such as congenital and acquired anomalies of the thoracic
      aorta and its branches, pulmonary arteries and veins, superior and inferior venae
      cavae, and azygos and hemiazygos veins. Other entities such as postoperative
      changes, massive pulmonary embolism, false ventricular aneurysm, and esophageal
      varices can also be misinterpreted. Important radiographic features that help
      distinguish these vascular structures from true neoplasms include proximity to
      known vascular structures, smooth margination, mural calcification, round or oval
      configuration, poor or nonvisualization in one of two orthogonal views, and
      absence or altered position of normal vascular structures. Knowledge of patient
      history and a detailed understanding of normal mediastinal anatomic structures
      and common variants help in making the correct diagnosis. Familiarity with these
      entities will result in the proper, most cost-efficient evaluation.

PMID- 7569135
TI  - 1994 plenary session: imaging symposium. Critical pathways in the management of
      breast disease: introduction.

PMID- 7569134
TI  - From the archives of the AFIP. Musculoskeletal angiomatous lesions: radiologic
      pathologic correlation.
AB  - Vascular lesions of bone and soft tissue are relatively common musculoskeletal
      neoplasms. Hemangioma is the most frequently encountered angiomatous lesion.
      Osseous hemangioma commonly involves the spine and calvaria and often has a
      characteristic radiographic appearance, with either coarsened trabeculae lying
      adjacent to the vascular channels or multifocal lytic areas creating a honeycomb
      pattern. Soft-tissue hemangioma is the most frequent soft-tissue neoplasm of
      infancy and childhood. Radiography and computed tomography (CT) may show
      phleboliths in cavernous soft-tissue hemangioma. The magnetic resonance (MR)
      imaging appearance, however, is often more distinctive, because fat overgrowth
      and serpentine vascular channels can be seen. Lymphangioma usually occurs in the
      neck and axillae of young children as a soft-tissue mass composed of large
      cavernous spaces and is well evaluated with CT, ultrasound, or MR imaging.
      Vascular lesions can also diffusely involve both bone and soft tissue in
      angiomatosis. A group of more aggressive vascular neoplasms, including
      hemangioendothelioma, hemangiopericytoma, and angiosarcoma, may have a
      nonspecific imaging appearance; however, the vascular pattern can be recognized
      in some cases, allowing radiologic diagnosis. Imaging is important throughout the
      evaluation of angiomatous lesions for detection, diagnosis, preoperative
      assessment, and treatment.

PMID- 7569136
TI  - Critical pathways in the analysis of breast masses.

PMID- 7569137
TI  - Critical pathways in analyzing breast calcifications.
AB  - Screening-detected microcalcifications are responsible for more benign biopsy
      results than any other mammographic lesion. The management of these lesions comes
      at a large cost in terms of morbidity and dollars spent. Both costs and morbidity
      could be reduced by decreasing the number of surgical biopsies. This could be
      accomplished by increasing the positive biopsy rate and by substituting core
      needle biopsy for surgical biopsy when appropriate. To increase the positive
      biopsy rate, we need to improve the preoperative evaluation of
      microcalcifications. A scheme is presented for the mammographic evaluation of
      these microcalcifications and for the appropriate use of core biopsy in the
      management of these lesions.

PMID- 7569138
TI  - Critical pathways in using breast US.

PMID- 7569139
TI  - Critical pathways in percutaneous breast intervention.

PMID- 7569141
TI  - CHORUS: a computer-based radiology handbook for international collaboration via
      the World Wide Web.
AB  - To facilitate collaboration among physicians, a computer-based radiology handbook
      was developed and published electronically via the World Wide Web on the
      Internet. This system, called CHORUS (Collaborative Hypertext of Radiology),
      allows physicians without computer expertise to read documents, contribute
      knowledge, and critically review the handbook's content by using a simple,
      graphical user interface from virtually any type of computer system. CHORUS
      contains 1,168 "note-card" documents that describe radiologic findings;
      differential diagnoses; technical information; and pertinent anatomy, pathology,
      and physiology. Documents are indexed by title and by organ system and are linked
      to related documents. Data entry forms allow physicians to comment on published
      documents, submit new documents, and review submitted documents. CHORUS uses
      public-domain technologies to present useful, easily accessible knowledge for
      education and clinical decision making, and it provides a medium for
      international medical collaboration via the Internet.

PMID- 7569140
TI  - Critical pathways for the future: MR imaging and digital mammography.

PMID- 7569142
TI  - The AAPM/RSNA physics tutorial for residents. Introduction to emission CT.
AB  - The article explores the fundamentals of emission computed tomography (CT) from a
      nonmathematical approach. Tomographic images reveal the internal distributions of
      radioactivity in three-dimensional objects, and thus allows anatomic localization
      and improves contrast. Tomography requires a stable distribution of
      radionuclides, uniform detector response, an accurate center of rotation, and a
      complete set of projections. In emission CT, a large number of measurements,
      called projections, are collected at various angles about the patient during the
      examination. This information is organized by the angles of acquisition into a
      stack, called a sinogram. Each projection is modified by applying a
      reconstruction filter (eg, ramp or windowed reconstruction filters). These
      modified projections are backprojected to form the transverse tomographic images.
      The quality of tomographic images generated from filtered backprojection depends
      on the underlying assumptions about the projections. Typical artifacts that
      result from violations of these assumptions include motion, uniformity, and
      attenuation artifacts. In addition, an inaccurate center of rotation,
      insufficient angular sampling, and errors in selection of pixel size can result
      in poor-quality reconstructed images.

PMID- 7569144
TI  - [Population biology of Posthodiplostomum namum Dubois, 1937 (Trematoda,
      Diplostomidae) in Jenynsia lineata and Cnesterodon decemmaculatus (Pisces,
      Atheriniformes), of Chis-Chis Lagoon, Province of Buenos Aires, Argentina].
AB  - The characteristics of the population dynamics of Posthodiplostomum nanum have
      been studied in two of its intermediate hosts, using prevalence, intensity and
      maturity of the metacercariae, considering the influence of the water
      temperature. In addition to this some ecological implications are described.
      There were made 18 samples monthly or bimonthly from may 1986 until march 1989,
      1113 fishes were captured out of which 956 metacercariae were obtained. P. nanum
      was present along the year, having significant seasonal variation in prevalence
      and intensity of infestation. It was observed that the water temperature is a
      relevant factor in the maturation of the parasite. The values of the prevalence
      and intensity of infestation were higher in Jenynsia lineata than in Cnesterodon
      decemmaculatus. This could be explained by various factors: a) distribution of
      the first intermediate host; b) behavior of the second intermediate host and c)
      individual physiological differences of each host, specially in relation to
      reproduction. The relation S2/X fluctuated during the whole year, indicating the
      recruitment-period (autumn, spring) and the nonrecruitment-period (winter,
      summer) of metacercariae.

PMID- 7569143
TI  - A real-time, flat-panel, amorphous silicon, digital x-ray imager.
AB  - As part of the development necessary for implementing a fully digital radiology
      department, the authors have investigated thin-film photodiodes and transistors
      for use in new photoelectronic imaging devices. One such device, a large-area,
      flat-panel, amorphous silicon imaging array, has been developed and is currently
      being tested. The array has a format of 512 x 560 pixels, a pixel-to-pixel pitch
      of 450 microns, and an area of 230 x 252 mm2, making it the largest self
      scanning, solid-state imaging array developed to date. The array is used in
      conjunction with an overlying x-ray converter. Although specifically designed for
      megavoltage imaging, the device can produce high-quality, low spatial resolution,
      diagnostic x-ray images. Qualitative comparisons of array images of
      anthropomorphic head, chest, and pelvic phantoms and a spatial resolution pattern
      suggest that much of the information content of the film images at low spatial
      resolution is present in the corresponding array images. Current trends in the
      development of large-area, flat-panel imaging technology hold the promise of
      higher resolution arrays in the near future.

PMID- 7569145
TI  - Density and habitat use of primates at an Atlantic forest reserve of southeastern
      Brazil.
AB  - About 58.3 km of transects were surveyed throughout 21,800 ha of an Atlantic
      forest reserve of southeastern Brazil, yielding habitat preference data and
      density estimates for three of the four primate species present. The densities
      were calculated using the "Fourier Series Estimator" and were 10.5, 2.2 and 1.2
      groups/km2 for Callithrix geoffroyi, Cebus apella robustus and Callicebus
      personatus personatus, respectively. Alouatta fusca fusca although present, was
      not seen during the survey. C. geoffroyi was spotted predominantly in the low
      strata of secondary forests while C. a. robustus preferred the higher strata of
      primary forests. The encounters with C. p. personatus were rarer but the species
      seems to occur in the middle strata of both primary and secondary forests. Local
      populations were estimated at 1644, 344 and 181 groups for these three species,
      respectively. With the exception of A. f. fusca which seems to occur at extremely
      low numbers, the densities for the other species are within the range of reported
      values for other species of these genera.

PMID- 7569146
TI  - [Histology and histochemistry of the kidney and ureters of the Caiman crocodilus
      yacare (Daudin, 1802)--Crocodilia Reptilia)].
AB  - The elongated kidneys of Caiman crocodilus yacare are found in pairs and have two
      lobes. Each lobe is crossed lengthwise down the middle by the renal vein and
      artery along which there are the renal corpuscules in groups of two or four which
      delimit the medullar renal region. These corpuscules are generally poorly
      developed and there is a center of connective tissue with few capillary loops.
      The Bowman capsule is of pavement or cubic epithelium and leads into a narrow,
      short, non-secretory neck segment composed of cubical cells followed by tubulus
      contortus with brush borders against the lumen and the distal tubule with cubic
      epithelium brush borders. In the renal cortical region are the median tubulus
      with cylindrical and granular epithelium and the smaller collecting canals which
      flow into larger collecting canals which flow along the renal border. Among the
      various tubular parenchyma segments there is a network of blood vessels which
      lead into the renal vein and into a renal afferent vein. Abundant fat granular
      bodies and lipid droplets are observed in the proximal and median tubules. The
      collecting canals and ureters show PAS positive granules in their cells.

PMID- 7569148
TI  - [Biophysical profile in twin pregnancy: prospective study].
AB  - The biophysical profile is an excellent test for assessment of the fetoplacental
      unit, for analyze is value in twin gestation, we study prospectively 81 multiple
      gestations. The fetuses were examined weekly antepartum. We use the modified
      profile of Manning which include only the sonographic criteria: the figures for
      predict stillborn were: sensitivity of 66.7%, specificity of 98.8%, positive
      predictive value of 50% and negative predictive value of 99.4% and predict
      between distressed and healthy fetus of a pair; 94.6% of fetus perform good
      biophysical profile score twenty minutes. We conclude that the fetal biophysical
      profile is the elective tool in the assessment of twin gestations.

PMID- 7569147
TI  - [Intrapartum fetal distress].

PMID- 7569149
TI  - [Hysteroscopic study in patients with abnormal uterine bleeding].
AB  - The experience of hysteroscopy performed in our Service in Abnormal Uterine
      Bleeding (AUB) is presented in order to show the utility of this procedure as a
      diagnostic method and compare these results with Dilatation and Curettage (DC).
      Eighty five patients underwent diagnostic hysteroscopy procedure, followed by DC;
      54 were postmenopausal (63.6%) and 31 were premenopausal (36.4%). The distention
      media used was liquid. In 47 patients (55.2%) the hysteroscopic diagnostic was
      normal or atrophic endometrium, in 16 patients (18.8%) was hyperplasia, in 17
      patients (20%) was endometrial polyp, 4 cases (4.7%) were described as cancer and
      in 1 case (1.3%) the diagnostic was bone metaplasia. We compared the results with
      the histology of DC obtaining a correlation of 93%. These results confirm the
      high accuracy of this procedure as a diagnostic method in uterine bleeding
      regarding its specificity and sensibility.

PMID- 7569150
TI  - [Double-blind method of the effect of menopause symptoms, lipid profile, and
      endometrial thickness of continuous therapy with estradiol valerate and
      medroxyprogesterone acetate].
AB  - Continuous combined therapy (CCT) using estrogens and progestagens has appeared
      as an alternative to avoid vaginal bleeding, which is characteristic of
      sequential hormone therapy, and the main reason for the stopping treatment.
      Irregular vaginal bleeding can occur at the beginning of treatment, but it has
      been observed that after a few months patients are in amenorrhea. Fifty
      postmenopausal women were studied in order to evaluate the clinical outcome. Half
      of them were treated with a product containing 2 mg estradiol valerate and 2.5 mg
      medroxiprogesterone acetate, while the other half received a placebo. Menopause
      symptomatology was recorded as described by Blatt-Kupperman, depression was
      evaluated with the use of Hamilton's test, lipid profile by enzymatic methods and
      endometrial thickness by transvaginal ultrasonography. Patients were evaluated at
      the beginning, third and sixth month of the study, following a double blind
      methodology. Symptomatology diminished both in patients under CCT and using
      placebo, although improvement was significantly greater in patient under CCT.
      Thus in the hormone treated group the Blatt-Kupperman score fell from 12.1 to 6.4
      and 3.2 in the third and sixth month respectively, while in the group receiving
      placebo the score fell from 11.5 to 6.3 in the third month and raised to 7.4 in
      the sixth month. Hamilton's test showed a significant improvement of depression
      only in patients under hormone therapy. Nineteen out of twenty five women using
      CCT had vaginal bleeding, showing no changes in the endometrial thickness during
      the study. Finally, HDL-cholesterol was raised in 14.5% while LDL-cholesterol was
      lowered in 18.7% (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569152
TI  - [Minimally invasive laparoscopic hysterectomy: Pelosi's single puncture
      technique].
AB  - The purposes of this paper were to determine the indications, feasibility,
      outcome, complications and costs of laparoscopic hysterectomy utilizing the
      Pelosi single umbilical puncture technique and to introduce in Latinoamerica this
      minimally invasive and inexpensive alternative of laparoscopic hysterectomy. Ours
      results suggest that laparoscopic hysterectomy using a single umbilical puncture
      approach is a safe, inexpensive and effective alternative when compared with
      other techniques of laparoscopic hysterectomy.

PMID- 7569151
TI  - [Triplet and quadruplet pregnancy: management and perinatal outcome].
AB  - The frequency of multiple pregnancies with more than two fetuses has increased
      considerably since the introduction of methods of ovulation induction, in vitro
      fertilization, and embryo transfer. We have analyzed the evolution,
      complications, delivery and perinatal outcome of 23 triplet and 3 quadruplet
      pregnancies occurred during a four-year period in one medical center. The most
      frequent complication was preterm labor (62%). The mean gestational age at
      delivery was 32.5 weeks for the quadruplets and 31.5 weeks for the triplets and
      the mean birth weight was 1461 and 1526 for quadruplets and triplets,
      respectively. Perinatal mortality for the whole group was 148/1000.

PMID- 7569153
TI  - [Cesarean section: Pelosi's simplified technique].
AB  - A new technique of cesarean section is introduced. This new minimally invasive
      procedure offers several advantages: simplicity, cost-effectiveness, faster
      recovery period than the traditional cesarean section technique, and it is
      associated with minimal morbidity.

PMID- 7569154
TI  - [Total parenteral nutrition in severe hyperemesis gravidarum].
AB  - Eight patients with severe HG, were treated through parenteral nutrition. This
      treatment was formulated as aminoacid, sucrose solution and fat solution (3 of 8
      cases), blended with vitamins electrolites and oligoelements. The procedure
      lasted 5 at 16 days conforming a total of 77 days. Seven newborns were term
      delivery, and one case was missed abortion. Like this, there were no
      complications detected and clinical wellbeing was reached, successfully.

PMID- 7569155
TI  - [Liver cirrhosis and pregnancy].
AB  - A clinical case of a woman 25 year old with Laennec's cirrhosis at 18th, week of
      gestation was admitted in our hospital. In the 30th week a cesarean section was
      performed, resulting a healthy infant. The infrequency relationship between
      pregnancy and cirrhosis is discussed an a review of the literature is presented.

PMID- 7569156
TI  - [Laparoscopy: an alternative to second-look laparotomy in ovarian cancer].

PMID- 7569158
TI  - [Malignant Brenner tumor of the ovary].
AB  - One case of Malignant Brenner Tumor is presented. Clinical and Anatomo
      Pathological aspects are review.

PMID- 7569157
TI  - [Complicated placental chorioangioma: infrequent cause of premature labor].
AB  - We report a case of a 32 week pregnant patient who was admitted to our ward in
      preterm labor. After delivery, the examination of the placental tissue showed a
      large pedunculated tumor, complicated with torsion. Histology of the tumor
      revealed a placental chorioangioma. We propose that the complication of the tumor
      is the etiologic factor that brought about preterm labor in this patient.

PMID- 7569159
TI  - [Prenatal diagnosis].

PMID- 7569160
TI  - [Size reduction of uterine myomas with monthly administered leuprolide acetate].
AB  - Six patients with symptomatic leiomyomata uteri and in whom surgical treatment
      was indicated received, during 3 months, intramuscular leuprolide acetate, 3,75
      mg monthly, in order to 1) achieve a reduction of myomata size and 2) recover an
      anemic patient before surgery. In every patient, amenorrhea was induced since the
      second month of treatment. A significant decrease of myomas sizes was achieved.
      The reduction of the volume of the largest myoma in each case, varied between 51%
      and 77% (x = 60% +/- ES 4,3) LH and estradiol plasma levels diminished
      significantly and FSH did not changed in response to treatment. Side effects were
      well tolerated. Hot flashes were present in all patients, headaches in 2 and loss
      of strength in 2. Surgery was accomplished after 3 months of treatment.
      Myomectomy was performed in 5 cases and total hysterectomy in 1. Uterine
      shrinkage and the period of amenorrhea induced by Lupron-depot facilitated
      hysterectomy and myomectomy techniques and the recovery of one patient with a
      severe anemia.

PMID- 7569161
TI  - [Evaluation of the external cephalic version in the management of dystocia].
AB  - We studied 45 patients with fetal malpresentations in a controlled trial, in
      which external cephalic version with tocolysis was performed. The final version
      rate was 73%, with a 49% of cesarean section in the study group compared with 87%
      in the control group. The most important factors related with successful version
      were type of presentation and parity. No important maternal of fetal
      complications were noted.

PMID- 7569162
TI  - [Cystic hygroma. Antenatal diagnosis and clinical management].
AB  - Nine cases of cystic hygroma in pregnancy diagnostic by ultrasound are presented.
      Chromosomal abnormalities accompany in 7 cases occurred, with, great frequency of
      "Turner Syndrome". The prognostic of this congenital malformation, has relation
      with the chromosomopaty and the difference between septal and nonseptated cystic
      hygroma.

PMID- 7569163
TI  - [Laparoscopy assisted vaginal hysterectomy at the Dr. Sotero del Rio Hospital].
AB  - Twenty three cases of vaginal hysterectomy performed between june 1993 and june
      1994 with the aid of laparoscopy were analyzed in Dr. Sotero del Rio Hospital.
      Average ages, parity, date of previous surgeries and associated pathology do not
      differ from the general population of the patients of the hospital. The results
      obtained in our series show that the procedure presents comparative advantages if
      compared with the classical abdominal hysterectomy by shortening the
      intrahospitalary stay, improving the postsurgical pain and the ventilating
      mechanic and by contributing to a faster return to work. The complication
      observed are normal for this type of surgery, however, a proper previous training
      in laparoscopic surgery and vaginal surgery is essential to limit these
      complications to a minimum.

PMID- 7569164
TI  - [Cyto-histologic evaluation of parametrial involvement in cervico-uterine cancer
      using aspiration puncture guided by transvaginal echography].
AB  - Vaginal tact is not sufficient for staging the extension of cervical Ca in its
      adnexal compromise. The use of transvaginal echography with a cytological
      hystological parametrial biopsy allow the diagnosis to be certified. In 23 cases
      studied, 21 epidermoid carcinoma and one adenocarcinoma related with of original
      cervical tumor were revealed. The clinical staging had a 8.3% error margin.

PMID- 7569165
TI  - [Nonimmunological hydrops fetalis. Experience with 33 cases].
AB  - A retrospective study of all perinatal autopsies done during 11 years at hospital
      SBA showed 33 cases of nonimmunologic fetal hydrops (1.83% of all perinatal
      autopsies). The incidence was 1/3624 liveborn babies. Intrauterine fetal
      infections and chromosome genetic abnormalities accounted for 27.3% each; and in
      15.2% of the cases some pathology of pregnancy was identified (including
      twining). All the cases showed severe anemia and in 58% of them pulmonary
      hypoplasia was identified. Moreover 31% of the cases showed renal hypoplasia. A
      placenta megaly was identified in 100% of the cases studied. The three most
      important mechanisms associate with the genesis of nonimmune fetal hydrops are:
      chronic intrauterine anemia, hypoproteinemia and intrauterine fetal heart
      failure.

PMID- 7569166
TI  - [Color Doppler of the utero placental territory and its relationship with the
      placental localization: normal and elevated resistance groups].
AB  - Forty two pregnancies of gestational age between 20 and 40 weeks were studied, 26
      with normal uterine artery resistance; Group A, and 16 with elevated UA
      resistance; Group B. Three categories of placental location were established:
      Type I; central, Type II; partially lateralized including uterine midline, Type
      III; completely lateralized not including uterine midline. A Diasonic doppler
      duplex color equipment was used to assess the systole/diastole ratio (s/d ratio).
      Five different pints of the uteroplacental vascular territory were evaluated in
      each patient; right and left bottom uterine artery (cervico ithsmical union),
      right and left top UA (laterally outstanding point of the uterine wall), and
      inter villous space. The results were analyzed with Statview (Macintosh)
      statistics software. Placental Type II, prevailed on Group A, Type III prevailed
      on Group B, Types II and III were predominantly located on the right side of the
      uterus. S/D ratio was higher in Group B than in Group A in all five sites. S/D
      rel was higher on left side than on right side measurements. On Group B, left
      placental side patients had significantly higher s/d rel on non placental uterine
      artery than right placental side patients. When one altered uterine Doppler flow
      value is found, all the uteroplacental vascular territory show a high resistance
      patterns. The lateral placental location patterns tend to express higher
      resistance values. Right lateral placental locations have even higher resistance
      values than left ones. The placental location classification is suggested as a
      screening method for detecting the group of patients in risk of having altered
      values of Uterine Doppler Flow Velocimetry.

PMID- 7569167
TI  - [Follicular and endometrial growth profiles in stimulated cycles with clomiphene
      citrate].
AB  - To study follicular and endometrial growth patterns in Clomiphene Citrate (CC)
      stimulated cycles, 50 CC cycles of 31 infertile women with patient Fallopian
      Tubes, were followed, 17 spontaneous conceptional cycles of fertile women were
      followed as controls. The pattern of follicular growth was similar in both groups
      until the day before ovulation in which CC cycles showed larger follicular
      diameters than spontaneous ones; 23.8 +/- 3.1 mm versus 21.6 +/- 2.9 mm (p =
      0.013). Follicular rupture occurred on day 16.1 +/- 2.9 in CC cycles, and on day
      15.1 +/- 1.85 on spontaneous conceptional ones. This suggests that the follicle,
      under the influence of CC, has to reach a larger critical mass to produce enough
      estradiol to revert the hypothalamic blockage produced by the drug, thus
      permitting the preovulatory LH surge. Endometrium under CC action, was always
      thinner than in natural cycles. On the day of follicular rupture, the CC cycle's
      endometrium measured 11.1 +/- 2.02 mm and the natural cycle's endometrium
      measured 10.6 +/- 1.8 mm (ns). This finding could be attributed to a
      antiestrogenic effect of CC on the endometrium. It is concluded that cycles under
      CC action have different follicular and endometrial growth patterns than
      spontaneous conceptional cycles.

PMID- 7569168
TI  - [2 infrequent vulvar tumors].
AB  - Two cases of malignant vulvar tumors are presented: a malignant Melanoma and a
      case of Carcinoma of the Bartholin Gland. Both were diagnosticated during 1993 in
      the Obstetrics and Gynecology Department of Dr. Felix Bulnes Cerda Hospital.
      Clinical and anatomophatological aspects are studied.

PMID- 7569169
TI  - [Spontaneous regression of a cystic hygroma].
AB  - A case of a nonseptated cystic hygroma with spontaneous resolution in utero is
      presented. The clinic, sonographic, and morphologic findings as well as the
      prognosis of septated and nonseptated cystic hygromas are discussed.

PMID- 7569171
TI  - [Mycoplasma infections].

PMID- 7569172
TI  - [Recognition at world level of Professor Dr. Luis Tisne Brousse].

PMID- 7569170
TI  - [Human immunodeficiency virus (HIV) infection in obstetrics and gynaecology].
AB  - HIV infection is increasingly affecting the practice of obstetrics and
      gynaecology. Gynaecological problems include an increased risk of sexually
      transmitted diseases and other genital infections in HIV positive women. Also
      cervical neoplasia is more common, more severe and progresses more rapidly. The
      risk of infection to the surgeon during surgical procedures on HIV positive women
      can be minimized by simple universal precautions. Pregnancy does not affect the
      course of HIV infection and neither is routine management of antenatal care
      altered by the infection. However, routine testing of all pregnant women for HIV
      would enable reduction of the risk of vertical transmission of HIV to the fetus
      (in Chile about 25%). Levels of vertical transmission could be reduced
      substantially by using zidovudine in pregnancy (and in the neonate), by cesarean
      section before active labour and by not breast feeding.

PMID- 7569173
TI  - Fluticasone propionate--an update on preclinical and clinical experience.
AB  - Fluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti
      inflammatory activity which has been effectively used, intranasally, as therapy
      for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP
      has shown significant therapeutic efficacy in the management of asthma.
      Fluticasone propionate is a highly lipophilic molecule with good uptake, binding
      and retention characteristics in human lung tissue. Fluticasone propionate has
      high glucocorticoid receptor selectivity and affinity, demonstrating rapid
      receptor association and slow receptor dissociation. In vitro, FP has been shown
      to potently inhibit T lymphocyte proliferation, cytokine generation, tumour
      necrosis factor alpha (TNF-alpha)-induced adhesion molecule expression,
      interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate
      induced mast cell proliferation, while promoting secretory leucocyte protease
      inhibitor production and eosinophil apoptosis. In human studies, FP has
      demonstrated marked vasoconstrictor potency in normal subjects and inhibited
      antigen-induced mucosal platelet activating factor/eicosanoid production, T
      lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild
      asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells,
      with an accompanying reduction in eosinophil and mast cell markers. Clinical
      studies have evaluated lung function, bronchial reactivity, exacerbation rates
      and oral corticosteroid-sparing effect. Results show that FP has at least twice
      the clinical potency of beclomethasone dipropionate and budesonide. This appears
      to be achieved without an accompanying increase in systemic effects, suggesting a
      therapeutic index which may be higher than other currently available inhaled
      corticosteroids.

PMID- 7569174
TI  - [Functional and anatomical results after surgical treatment of ruptures of the
      rotator cuff. 2: postoperative functional and anatomical evaluation of ruptures
      of the rotator cuff].
AB  - PURPOSE OF THE STUDY: The authors examined the anatomic condition and the
      function of the rotator cuff obtained after an average period of four years
      following surgical repair in a series of 100 full thickness rotator cuff tears.
      The aim was to assess the validity of Constant's scoring method and to analyse
      risk factors and the frequency of recurrent tears. MATERIAL AND METHODS: The
      series comprised 98 patients, 62 men and 36 women whose average age was 56 years.
      It included 69 tears of less than 2 cm in size (39 cases) or between 2 to 4 cm (3
      cases) of the supra-spinatus, 22 tears of the supra- and infraspinatus measuring
      between 2 to 4 cm, and 9 massive tears. The tendon of the long head of the biceps
      was pathological in 1/3 of cases. All 98 patients were operated on by the same
      surgeon using the same repair technique, and all followed ambulatory
      rehabilitation along the same principles of self-rehabilitation applied pre
      operatively. In each patient function was assessed using Constant's scoring
      method, and the condition of the repaired cuff was determined by ultrasonography
      at the time of clinical follow-up. The average follow-up period was 4 years (2 to
      6 years). RESULTS: Ultrasonography revealed intact cuffs in 65 per cent, thinned
      cuffs in 11 per cent and recurrent full thickness tears in 24 per cent of cases.
      The risk of recurrent tear increased with the extent of the tear to be repaired
      (57 per cent), in older patient (25 per cent) and with a higher level of post
      surgical occupational use (18 per cent). A drop in the post-operative Constant
      score had a predictive value for a full thickness recurrent defect. DISCUSSION:
      Constant's scoring method appears to be a reliable, reproducible method for
      analysing functional results following surgical repair of full thickness cuff
      tears and to reflect the anatomic condition of the repaired cuff. At clinical
      follow-up, the anatomic condition of the cuff is more determinant of final
      functional results than initial tear size. CONCLUSIONS: Assessment of functional
      results must be complemented by anatomic examination using ultrasonography in
      order to specify the size of any possible recurrent defect and to detect thinning
      of the cuff which cannot be identified by Constant's score. Analysis of the risk
      factors for recurrent tear led the authors to question the necessity of repairing
      massive tears in older patients and pointed to the valuable advantages of
      reinforcing fragile cuffs during initial repair especially in very active
      patients.

PMID- 7569175
TI  - [Recent post-traumatic luxation of the trapeziometacarpal joint. Apropos of 8
      cases].
AB  - PURPOSE OF THE STUDY: Eight cases of acute traumatic dislocation of the trapezio
      metacarpal joint treated by percutaneous pinning without ligamentoplasty are
      reported in order to evaluate this method. MATERIAL: Eight patients, two women
      aged 32 to 38 and six men aged 17 to 43, were treated for acute traumatic
      dislocation of the trapezio-metacarpal joint between 1986 and 1993. The injury
      happened in a road traffic accident in five cases, during a fight in one case,
      and in a fall in two cases. The mechanism of injury could be determined only
      twice as a longitudinal force applied on the first metacarpal bone with the
      trapeziometacarpal joint in flexion. The dominant hand was injured in five cases.
      The metacarpal base was always dislocated dorsally. Closed reduction was always
      easy but remained unstable. On the initial radiographs, one patient had a small
      fragment avulsed from the volar aspect of the metacarpal base, another had a
      small osteochondral fragment avulsed from the joint surfaces and two patients
      presented asymptomatic degenerative changes with osteophytes. METHODS: All
      patients were treated on the day of injury by reduction and stabilization by one
      (in four cases) or two (in four cases) percutaneous Kirchner wires followed by a
      scaphoid-type cast for six weeks. In only one case an arthrotomy was performed to
      remove a small osteochondral fragment lodged in the joint, and showed a
      disruption of the dorsal ligament. All patients were followed-up until the tenth
      postoperative week, and five of them were reviewed for this study between eight
      and seventy-eight months (mean 27.5 months) after injury. Enquiries were made
      about return to work, pain, stability, and range of motion, keypinch and grasp
      compared with the uninjured side. The joint was examined radiographically with
      particular attention to the presence of subluxation and degenerative changes.
      RESULTS: One patient with a dislocation of the five carpometacarpal joints had
      reflex algodystrophy; she was not seen for review. Five patients had a completely
      satisfactory early result at ten week's follow-up examination that maintained at
      late review for this study. There were no symptoms, no subluxations on the
      radiographs, and the patients had returned to work between ten to sixteen weeks
      (mean 11 weeks) post injury. The two patients with degenerative changes on the
      initial radiographs had early unsatisfactory results with early dorsal
      subluxation, loss of strength of 30 per cent, but no limitation of joint motion
      and pain in one case. DISCUSSION: Acute traumatic dislocation of the trapezio
      metacarpal joint is an uncommon injury; it may be associated with a small
      fragment of bone avulsed from the volar aspect of the metacarpal base or from the
      articular surfaces. Pequignot and coll. in 1988, and Fontes in 1992 recommended
      opened reduction and ligamentous reconstruction in acute injuries. Our experience
      indicates that closed reduction followed by stabilization by percutaneous pinning
      gives satisfactory results. An arthrotomy may be necessary when an osteochondral
      fragment avulsed causes incoercibility. CONCLUSION: Closed reduction followed by
      stabilization by percutaneous pinning gives good results in the treatment of
      acute traumatic dislocation of the trapezio-metacarpal joint. It finds its limits
      with patients with degenerative changes on the initial radiographs, and in this
      case ligamentous reconstruction, arthrodesis or arthroplasty might be advocated.

PMID- 7569176
TI  - [Late results of the treatment of the slipped upper femoral epiphysis (26 cases
      with follow-up study over 10 years)].
AB  - PURPOSE OF THE STUDY: The treatment of slipped capital femoral epiphysis (SCFE)
      has been well described by many authors. However, few studies report the results
      of treatment at very long term. The purpose of this study is to observe late
      results and to distinguish which factors can influence the development of
      osteoarthrosis. MATERIAL: Twenty-six patients (30 hips) with SCFE treated between
      1945 and 1980 were reviewed with a minimal follow-up of 10 years. The measure of
      the displacement was done in 3 groups: slipping inferior to 30 degrees, slipping
      between 30 degrees and 60 degrees and slipping superior to 60 degrees. There were
      14 cases in group 1, 12 in group 2 and 4 in group 3. Four cases had bilateral
      involvement. 24 hips underwent surgical treatment: 10 in situ fixation, 10
      orthopedic reduction and screw fixation, 2 cervical osteotomies and 1 Dunn's
      operation. 5 cases had no treatment or simple traction in bed and 2 cases had
      reduction and spica cast. METHODS: Clinical evaluation was done with the Merle
      d'Aubigne hip score and the radiographical revision on anteroposterior and
      Lauenstein projections. Osteoarthrosis was assessed according to the narrowing of
      articular space and the flattening of the head. RESULTS: Early complications: 4
      cases of chondrolysis appeared 3 times after orthopedic reduction and fixation.
      Two material effractions and one hyperreduction of the displacement were
      observed. Radiographic degradation was constant. 2 cases of segmental collapse
      were also seen, once associated with hyperreduction and once with material
      fixation. Revision: the average follow-up was 19 years (11 to 46 years). 20 hips
      (66 per cent) had very good functional results. 18 hips (60 per cent) had
      radiographic arthrosis. No statistic tests were done because of the small number
      of cases. However 9 out of 10 in situ fixation and 6 out of 10 reduction and
      fixation had very good results. When the residual slip was less than 40 degrees
      (12 cases), osteoarthrosis was never seen. 40 degrees represented the limit
      between arthrosic and non arthrosic evolution. The mean time of development of
      arthrosis was 25 years. DISCUSSION: The worst results appeared to happen after
      reduction and spica cast, cervical osteotomy and traction in bed. Best results
      after in situ fixation, Dunn's operation and no treatment. Reduction and fixation
      gave divided results. The osteoarthrosis increased with time. The limit of 40
      degrees as factor leading to osteoarthrosis was found to be nearly similar to
      that of others authors. Discrepancy was superior to 1 cm in 84 per cent of cases,
      but most of the time neglected or unknown by patients. CONCLUSION: In our series,
      osteoarthrosic hips are seen in 60 per cent cases. Radiographic degradation was
      constant after 25 evolution years. The hips with less than 40 degrees slipping
      after treatment have the best results and no arthrosis. Thus, in situ fixation is
      recommended for slipping inferior to 40 degrees. If displacement is greater than
      40 degrees, Dunn's operation or trial orthopedic reduction to obtain a reduction
      of slipping is preferred, according to the character (chronic or acute) of the
      slip.

PMID- 7569178
TI  - [Clinical evaluation of total knee prosthesis: comparative analysis of scores].
AB  - PURPOSE OF THE STUDY: Numerous scoring systems have been described for the
      evaluation of total knee arthroplasty. The aim of this study was to analyze the
      reality of the results and the differences between clinical evaluation scores.
      MATERIAL AND METHOD: We calculated the mean overall scores (Hungerford, Laskin,
      Hospital Special Surgery and Mansat) in a series of 89 PCA total knee
      arthroplasties with a mean follow-up of 4.5 years. We compared postoperative
      score values considered as borderline between poor and good results with survival
      curves. RESULTS: The mean values of the postoperative scores were very similar
      and showed no significant differences: Hungerford: 83 pts; Laskin: 80 pts; HSS:
      80 pts; and Mansat: 86 pts. The comparison between the four survival curves was
      statistically significant: the Hungerford curve was the most optimistic (62 per
      cent success at 8 years) when compared to the Laskin score (16 per cent success
      at 8 years). DISCUSSION: The scores do not express the same reality. For mean
      values close or identical to the scores, the quality of the results may be
      different. Our analytic method reveals considerable differences explained by the
      juxtaposition of clinical and functional parameters in the scores. The Hungerford
      and Mansat scores are principally based on clinical criteria while the Laskin
      score is more functionally orientated. The HSS score is more even handed.
      CONCLUSION: It is incorrect to appreciate the value of survival curves if the
      scores are based on functional criteria as these parameters will naturally
      deteriorate over time and therefore these scores do not reflect the real quality
      of the arthroplasty. The Knee Society Score is probably the most interesting
      system since functional and clinical parameters are separated.

PMID- 7569177
TI  - [Total arthroplasty, using Hardinge's approach, combined with trochanterotomy:
      comparative results of 200 cases].
AB  - PURPOSE OF THE STUDY: A retrospective study to compare the results obtained in
      our first 100 total hip prostheses inserted by Hardinge's approach and of the 100
      others inserted by trochanterotomy was undertaken. MATERIAL: In the
      trochanterotomy group the average age was 66 years; average follow-up was 26
      months. Using the Merle d'Aubigne score the initial score was 11.8. There were 65
      cases of centered hip arthritis. In the Hardinge group the average age was 65
      years; average follow-up was 28.3 months. The Merle d'Aubigne initial score was
      12.3. There were 78 cases of centered hip arthritis. There were therefore no
      significant differences between the two groups and the two groups were
      comparable. METHODS: The quantitative variables (age, duration of operation,
      blood loss, blood transfusion, follow-up) were compared by Student's test. The
      qualitative variables (thrombo-embolic complications, dislocations, periarticular
      ossifications, acetabular radiolucency lines, non-union of the greater
      trochanter, gluteus medius palsies) were compared by the chi 2 test. RESULTS: We
      found no significative differences on neither the functional level nor on the
      orientation of the prostheses nor on the number of infectious complications
      between these two surgical approaches. Moreover, we found more complications such
      as thromboembolism and dislocations favoured by non-union of the greater
      trochanter in patients operated by trochanterotomy. These patients also had
      greater blood loss. In patients operated by Hardinge's approach, we found gluteus
      medius palsies (recovering secondarily); we also found a higher frequency of
      periarticular ossifications and a greater number of partial acetabular lines.
      DISCUSSION: Non-union of the greater trochanter appears in all the series of
      total hip arthroplasty by trochanterotomy. No technique permitted to avoid this
      complication which usually leads to pain and hip instability. This surgical
      approach is associated with higher blood loss. With Hardinge's approach there is
      no risk of non-union of the greater trochanter and blood loss is less important.
      The risk of gluteus medius palsy has to be taken in to account but digital
      dissection of the muscle fibers seems adequate to diminish the frequency of this
      complication. There is also a greater number of asymptomatic periarticular
      ossifications in our study but whose long term consequences are unknown.
      CONCLUSION: This study leads us to prefer the Hardinge approach for total hip
      arthroplasty. Our recent experience encourages us even because it permits
      osteoplastic ridge and total hip resumption. We use the trochanterotomy only for
      the most difficult cases specially hip arthritis secondary to severe dysplasia or
      congenital hip dislocations when a lowering effect of the great trochanter should
      also be associated.

PMID- 7569179
TI  - [Filling of bone defects using biphasic macroporous calcium phosphate ceramic.
      Apropos of 23 cases].
AB  - PURPOSE OF THE STUDY: The authors report their experience with the use of a
      biphasic macroporous calcium phosphate bone substitute. MATERIALS AND METHODS: In
      23 cases (22 patients) a biphasic macroporous calcium phosphate ceramic was used
      to fill a pathological bone defect. The ceramic used in this study was a
      macroporous (400 to 600 mu) component consisting of 60 per cent hydroxyapatite
      and 40 per cent beta-tricalcium phosphate. It was in the form of granules (2 to 3
      mm), sticks (20 x 5 x 5 or 10 x 5 x 5 mm) or custom made blocks. In 6 cases, the
      ceramic was used alone; in 12 cases with autologous bone marrow and in 5 cases
      with autologous cancellous bone grafts. In 14 cases, the bone defect was due to
      conservative treatment of a benign tumor, in 3 cases due to aseptic post
      traumatic non union, in 3 cases due to wide resection for malignant tumors of the
      pelvis and in 3 cases following osteotomy. Post operative assessment was made
      from clinical, radiographic and histological findings. RESULTS: 2 patients died 6
      and 8 months post operatively and 2 were lost to follow up at 2 and 5 months with
      both having good clinical and radiographic results when last seen. For the
      remaining 19 cases, the average follow-up was 20 months (from 6 to 62 months). No
      local, regional or general deleterious effects were noted. Radiologically the
      bone ceramic junction healed in all cases except 2 within 3 months. In these last
      two cases, healing required 6 and 7 months. No radiolucent line appeared around
      the ceramic. No stress fractures occurred in the substitute. Histologically, 3
      biopsies showed new bone formation throughout the ceramic with apposition of a
      well differentiated lamellar bone directly apposed to the ceramic. DISCUSSION:
      Animal experimentations have proven the interest of similar ceramics:
      macroporosity enhances bone rehabilitation and the biphasic characteristics
      associate the advantages of slow resorption of hydroxyapatite and more easily
      resorbed beta-calcium phosphate. No deleterious clinical, radiographical or
      histological effects were observed, confirming the biocompatibility of this
      substitute. Despite the poor mechanical properties of this macroporous ceramic
      before implantation, good clinical and radiographic results suggest improvement
      of these properties in the composite new formed bone-ceramic after implantation.
      CONCLUSION: We believe that macroporous biphasic ceramic is a good substitute for
      use in bone defects when good primary mechanical stability and contact with the
      host bone are present. Further clinical and experimental studies are necessary to
      determine the limits of such a substitute in terms of volume and to control its
      mechanical properties following implantation.

PMID- 7569180
TI  - [Flaps of the gastrocnemius muscles].
AB  - The authors expose different techniques and maneuvers used for dissection of
      gastrocnemius flaps with reference to the data reported in the literature and to
      the anatomical vascular basis. The use of muscular and myocutaneous gastrocnemius
      flaps and some modifications of the standard surgical technique aiming to gain
      more versatility are described, so that, the range of these flaps can be planned
      to cover the greatest part of the lower extremity of the leg.

PMID- 7569181
TI  - [Munchmeyer's disease in children].
AB  - The clinical features of two children with myositis ossificans progressiva are
      described. Skeletal malformations can be observed in many sites: hand, femur,
      tibia and spine. Phalangeal abnormalities (shortened hallux, hallux valgus) are
      essential to the diagnosis. We recommend systematic roentgenographic examination
      to search for other skeletal malformations for congenital hallux valgus in young
      children because it can be the first sign of myositis ossificans progressiva.
      Progression of disability does not seem to be influenced by any form of medical
      treatment. Surgical removal of ectopic bone is thought to be followed inevitably
      by rapid recalcification at the original site.

PMID- 7569182
TI  - [Progressive fragmentation of a bipartite patella: apropos of a case].
AB  - PURPOSE OF THE STUDY: Progressive dissolution of the supero-lateral fragment of a
      bipartite patella is reported. MATERIAL AND METHODS: The patient, a 44 year old
      professor of gymnastics, was examined for long standing anterior knee pain. For
      many years, his daily activities included forceful knee flexion exercises. Serial
      radiographs, between 1986 and 1990, revealed a progressive fragmentation of the
      accessory ossification center and accompanying calcific deposits in the lateral
      patellar retinaculum. RESULTS: Surgical excision of the calcific mass and
      accessory ossification center relieved the painful symptomatology completely,
      allowing the patient full normal function at one year's follow-up. DISCUSSION:
      The pathological findings were compatible with a dystrophic calcinosis associated
      with detritic synovitis. A pathogenic mechanism is hypothesized for this unusual
      and progressive course of a common condition: Repetitive trauma, in this case
      forceful knee flexion exercises, shear microscopic bony fragments of the poorly
      vascularized accessory ossification center. These microscopic fragments act as
      deposits of an apatite crystal which go on to induce the secondary soft tissue
      calcifications seen in our patient.

PMID- 7569183
TI  - [Functional and anatomical results after surgical treatment of ruptures of the
      rotator cuff. 1: Preoperative functional and anatomical evaluation of ruptures of
      the rotator cuff].
AB  - PURPOSE OF THE STUDY: In a consecutive series of 98 patients presenting 100 full
      thickness cuff tears and managed by the same medico-surgical team, the authors
      studied the correlation between preoperative shoulder function values and the
      anatomic lesions found at surgery. Predictive factors of tear size were evaluated
      and any elements that were likely to improve preoperative function were
      determined so that patients could be best prepared for surgery. The validity of
      preoperative radiographic assessment of lesions was examined. MATERIAL AND
      METHODS: Prior to surgery, each patient was given the same rehabilitation
      program, the same arthrotomographic assessment of lesions and each was rated
      functionally using Constant's scoring method. Preoperative radiographic
      assessment of lesions showed supra-spinatus tears in 69 per cent, combined
      supraspinatus and infraspinatus tears in 22 per cent, and tears involving the
      supraspinatus, infraspinatus and subscapularis in 9 per cent. RESULTS: The
      preoperative Constant score averaged 46/100 points. The score was higher when
      patients had been prepared by preoperative rehabilitation to overcome stiffness.
      The optimum duration of rehabilitation was found to be 3 months (p < 0.05).
      Active range of motion was 90 per cent of normal in 84 per cent of cases. The
      patients in this series therefore underwent surgery more for continuing severe
      pain (25 per cent) and muscle weakness (86 per cent) than for reduced active
      motion. DISCUSSION: Examination of the correlations existing between an anatomic
      lesion and the preoperative rating of shoulder function shows that the Constant
      preoperative score provides a good prediction of the size of the tear to be
      repaired (p = 0.0063). The greater the tear size, the lower the preoperative
      Constant sore is. Active range of motion (especially in abduction and external
      rotation) and muscular strength are factors with the most predictive value
      contrary to pain and discomfort which are influenced by tear size. CONCLUSION:
      Preparing patients suffering full thickness cuff defects through preoperative
      rehabilitation to overcome stiffness provides the best conditions for surgery.
      Constant's functional scoring method gives a reproducible and reliable reflection
      of the anatomic rotator cuff lesion to be repaired. Its use for preoperative
      rating is useful for determining a reference value for function prior to surgery.

PMID- 7569184
TI  - [Fibrodysplasia ossificans progressiva. Apropos of a case].
AB  - PURPOSE OF THE STUDY: Fibro-dysplasia ossificans progressive is a rare inherited
      disease, presumably transmitted as an autosomal dominant defect. The high level
      of spontaneous mutations explains the sporadic cases. Pre symptomatic diagnosis
      could be actually evoked by the association of progressive ossification of soft
      tissues with congenital anomalies of bones (metacarpal and metatarsal). The
      purpose of this study is to report a clinical case with a very severe course.
      CASE REPORT: A 10-year-old boy developed progressive ossification of muscles and
      soft tissues in multiple sites neck, back, shoulders, elbows, hips and knees. The
      clinical course was severe due to the ankylosis of all the joints and the
      decrease of pulmonary reserve with fixation of the chest wall. A malformation of
      the great toes facilitated the diagnosis. DISCUSSION: This pattern of heterotopic
      ossification together with the congenital malformations of the great toes defines
      the developmental phenotype for fibrodysplasia ossificans. A slow course with
      successive thrusts occurs. Ossification progressively involves tendons, ligaments
      and the connective tissue of skeletal muscles. Excision of heterotopic bone is
      futile as the trauma of the operation can lead to the stimulation of new
      heterotopic ossification at the operative site. Surgery is only useful for biopsy
      and histological study reveals bone metaplasia. The mature heterotopic bone is
      histologically indistinguishable from mature skeletal bone. The non skeletic
      muscles are characteristically spared from ossification. Premature death often
      results from respiratory failure due to fixation of the thoracic cage. The
      pathogenesis and the treatment of the disorder are unknown.

PMID- 7569185
TI  - [Bone reaction to contact with a granulated titanium surface. Apropos of 101
      total hip prostheses with six years follow-up].
AB  - PURPOSE OF THE STUDY: The failures of cemented hip prosthesis have prompted
      research into a new process of fixation and a new design of the system. Stability
      is achieved by adherence the bone onto a blasted titanium surface. The shell is
      implanted without screws. The stem has an anatomical shape to improve metaphyseal
      fixation of the femur. MATERIAL AND METHODS: The rugosity of the blasted titanium
      surface which has an average depth of 50 millimicrons allows new bone-growth
      without any fibrous interposition. Bone ingrowth starts from the third week
      onward and within two years a homogenous bone sheath is produced. Several
      experiments on animals have shown the quality of the bone-growth onto this
      blasted surface. The bone reaction has the same qualities as a hydroxy-apatite
      coating. It is of better quality than other titanium surfaces. The press-fit
      obtained by the shape allows this bone-growth. The reliability of this biological
      fixation is enabled for the shell by the perfect distribution of loads due to the
      hemispherical shape and the greatest possible thickness of the polyethylene. For
      the stem, the purely metaphyseal fixation appears to be a very important factor
      to enable painless long term stability. Another advantage of this method of
      fixation is that the prosthesis can be removed without any damage to the bone and
      can be reimplanted without any artificial fixtures with excellent results.
      RESULTS: Histological results. Within a few weeks a new strip of bone will settle
      onto the porous metal without any fibrous interposition. This strip is connected
      to the cortical bone by small brackets of bone which gradually thicken over the
      months and guarantee anchorage. Radiological results. In 1 per cent of all cases
      a border or a gap has formed around the shell; there is no migration. Around the
      proximal part of the stem thin ribs in tension appeared at the beginning and over
      the months the width of these increased. Within two years they had filled the
      space between the metal and the cortical bone. Around the distal part of the
      stem, which is smooth, there is no bone-growth. Clinical results. In nearly 94
      per cent of cases a perfect result was obtained which could only be achieved if
      the prosthesis was perfectly stable. There was mild pain in only 4 per cent of
      cases. Revision and observation. Two revisions for ceramic head fracture
      confirmed that it was possible to remove the prosthesis without damage to the
      bone. DISCUSSION: A correct pressure distribution on bone would appear desirable
      for the two components. For the acetabulum a thick layer of polyethylene and for
      the stem a metaphyseal anchorage are desirable. CONCLUSION: It is perhaps too
      early at this stage to speculate on the long term results. Nevertheless as of now
      we observe that the principle of a metaphyseal fixation significantly decreases
      the incidence of mild pain. On the other hand, the follow-up of nearly seven
      years of bone fixation on a blasted titanium surface would seem sufficient to
      show us that this method has proven to be a significant improvement.

PMID- 7569186
TI  - [Evaluation of laxity, rigidity and compliance of the normal and pathological
      knee. Application to survival curves of ligamentoplasties].
AB  - PURPOSE OF THE STUDY: The aim of this prospective study was to measure the
      stiffness of the ACL in normal knees, ACL deficient knees and after ACL
      reconstructions or meniscectomies. Stiffness is a physical quantity which
      expresses objectively the mechanical efficiency of the ACL. MATERIAL AND METHODS:
      1502 tests were performed on: 480 normal control knees, 191 acute tears and 171
      chronic instabilities pre and post-operatively, 60 extra-articular plasties, 30
      meniscectomies and 64 arthritic knees before and after a cruciate sparing
      arthroplasty. The force displacement measurements were made on radiograms of the
      medial and lateral compartment of each knee at 20 degrees flexion by applying a
      postero anterior force from 0 to 300 N with increments of 50 N. The stiffness is
      the slope of the F/dl curve. RESULTS: In the normal knee the medial compartment
      is fixed. Its stiffness is 13.8 x 10(4) N/m and does not depend on age and sex.
      The diagnosis of ACL rupture is made when the right/left difference on the medial
      compartment is at least 4 mm at 250 N. The lowest level for an accurate
      diagnostic is 180 N. The positive predictive value is 99 per cent. In acute tears
      the stiffness is 2.5 x 10(4) N/m. It is 3.4 x 10(4) N/m in chronic instability (p
      = 0.0001). When a meniscectomy was performed in chronic instability the stiffness
      decreases significantly (M+: 3.7 x 10(4) N/m; M-: 2.1 x 10(4) N/m) (p = 0.03).
      After a bone-patellar tendon-bone plasty (BPTB) the stiffness was 6.0 x 10(4) N/m
      and did not decrease with the passage of time but after the extra-articular
      plasty (EAP) the stiffness was 4.7 x 10(4) N/m after 24 months and 3.0 x 10(4)
      N/m after 60 months. Meniscectomy decreases the stiffness in both procedures,
      however it remains stable after BPTB, but decreases with the passage of time
      after EAP. DISCUSSION: Stiffness is a biomechanical parameter of knee ligaments.
      It is highly correlated with the clinical symptoms of instability (p = 0.0001).
      It is more accurate than laxity which is a numerical value without mechanical
      significance. CONCLUSION: This method gives functional information on the ACL
      deficient knee. It is the more precise method for the diagnostic of ACL rupture
      with an efficiency of 98.5 per cent. It has a high prognostic value after ACL
      surgery and can be considered as the mechanical survival of the plasty.

PMID- 7569187
TI  - [Arthrodesis of the ankle under arthroscopy. Apropos of 10 cases reviewed after a
      year].
AB  - PURPOSE OF THE STUDY: The technique, results and indications for arthroscopic
      ankle fusion are detailed and compared with open technics. MATERIAL AND METHODS:
      10 arthroscopic ankle fusions were performed between 1991 and 1993. This
      procedure was used in 4 cases of rheumatoid arthritis, 5 cases of osteoarthritis
      and 1 case of joint destruction consecutive to hemophilia. All patients were
      followed until fusion with an average follow-up of 12 months. The quality and
      position of the fusion were analyzed clinically and on radiograms. RESULTS: 9
      patients obtained fusion in a neutral position and were able to walk with normal
      shoes. The average time to fusion was 14.5 weeks (8 to 40). 1 case failed and
      required reoperation after 15 months. No local complications were observed.
      DISCUSSION: Arthroscopic ankle fusion is a safe procedure with good results in
      cases with relatively little deformities. Its main interest lies in the low rate
      of complications. The technique does not increase the rate of fusion when
      compared to open technics. CONCLUSION: Arthroscopic fusion is recommended in
      cases with little to moderate deformities in the presence of poor wound healing
      factors.

PMID- 7569188
TI  - [Hallux valgus treated by shortening of the first phalanx with trans-epiphyseal
      impaction and adductor plasty. Apropos of 49 cases with 5-years follow-up].
AB  - PURPOSE OF THE STUDY: 49 cases of hallux-valgus were treated by a shortening of
      the phalanx with impaction according to the technic described by Regnauld,
      associated with a plasty of the adductor. Patients were evaluated with a follow
      up greater than 5 years. MATERIAL AND METHODS: 32 female and 5 male patients were
      treated. 63 per cent patients were between 30 and 60 years old. The preoperative
      average of metatarsus varus was 12 degrees 1. The length of first metatarsal was
      inferior to the second in 30 cases. The preoperative average of first phalange
      valgus was 30 degrees. Every operated foot had an Egyptian morphotype. Sesamoids
      were consistently dislocated. Associated lesion were: 19 flat feet, 10 round fore
      feet, 9 clinodactylies treated during the same procedure. RESULTS: They were
      evaluated according 3 Groulier's criteria: the correction of deformation, static
      disturbances, and professional activities. The phalangeal valgus was corrected in
      37 cases (72 per cent). 33 feet were painless (67 per cent). The dorsal flexion
      of the first toe was superior to 60 degrees in 38 cases (77 per cent). Metatarsus
      varus was consistently reduced. 2 permanent metatarsalgia and 4 plantar corns
      persisted. 76 per cent of operated patients were able to wear shoes normally with
      a normal perimeter of walking. At X-ray examination, the head of first metatarsal
      was unchanged in all cases. The joint space was normal in 39 cases (79 per cent).
      The base of first phalanx was normal in 25 cases (51 per cent). 37 feet had
      centered sesamoids. In total, we noticed: 37 very good and good results (72 per
      cent), 8 moderate results (17 per cent), bad results (9 per cent). DISCUSSION:
      The operative technic gives a stable shortening of the first phalanx without
      material and allows the early weight bearing. The abductor of the great toe is a
      stronger muscle than adductor, allows rotational correction and the alignment of
      the first phalanx on the first metatarsal. We agree with criteria of bad
      prognosis proposed by Groulier: age, valgus flat foot, the duration and the
      importance of deformation, the presence of osteoarthritis. CONCLUSION: The
      abductor plasty and soft tissue operation contributes to the durable correction
      of hallux valgus. Shortening must preserve the vascularization of the proximal
      end of the phalangeal. This operation should be reserved for young patients,
      without signs of articular cartilage degeneration and having an Egyptian foot.

PMID- 7569190
TI  - [Femoral lengthening by callotasis. A study of a series of 79 cases in children
      and adolescents].
AB  - PURPOSE OF THE STUDY: Results of femoral lengthening using callotasis method,
      with particular attention to the complications are presented. MATERIAL AND
      METHODS: 79 femoral lengthenings performed for limb length discrepancy in 75
      children and adolescents were studied. Etiology of the femoral shortening was
      congenital in 23 cases, post-traumatic in 20, post-infection in 14, neurologic in
      13, and miscellaneous in 9. Nine lengthenings were performed using the Judet
      lengthener and 70 using the Orthofix external fixator. We used gradual
      incremental distraction (callotasis). RESULTS: Average lengthening achieved was
      52 mm (range: 35 to 85), which represented a 17.7 per cent increase in femoral
      length (range 7.6 per cent to 64 per cent). There were 87 complications, i.e. 110
      per cent. Several complications were often encountered during one lengthening,
      thus, 23 lengthenings (30 per cent) were performed without any complication and
      49 (62 per cent) without additional unpredicted operations or anesthesia. All
      these complications were studied according to the stage (intraoperative,
      elongation, consolidation and delayed) in which they occurred and to their
      severity. They were assessed to establish their relationship to etiology of
      shortening, amount of lengthening and age. Intraoperative complications were rare
      (2 cases). In the distraction period, joint complications are the most frequent
      (33 complications), involving the hip 22 times and the knee 11 times; 28 healed
      without any problems, 14 needed reoperation and 1 dislocation of the hip led to
      an avascular necrosis. DISCUSSION: The incidence of joint complications did not
      seem to be less than that encountered with previous methods of lengthening. The
      author believes that systematic tenotomies performed in order to avoid such
      complications in congenital short femurs are abusive and have to be discussed
      case-by-case. Bony consolidation was achieved without additional surgery in 90
      per cent of cases. Eight patients had delayed consolidation but did not require
      surgery. Complicated consolidation was most commonly encountered in children less
      than 8 years old with congenitally short femurs. The author compared healing time
      according to the type of dynamization. A significant improvement was found when
      using a silastic collar (33.3 days/cm) in place of classical dynamization (46.6
      days/cm). CONCLUSION: The author believes that good results can be obtained by
      incremental distraction using uniplanar fixation. Results could be improved by
      proper fixator application, aggressive physical therapy and well-thought
      dynamization of the fixator.

PMID- 7569189
TI  - [Treatment of Morton neuroma by neurectomy. Apropos of 43 cases].
AB  - PURPOSE OF THE STUDY: Morton's neuroma is a frequent cause of metatarsalgia. Its
      diagnosis is clinical but progress in medical imaging: ultrasound, evoked
      potentials and above all MRI allows an improvement of para-clinical diagnosis.
      MATERIAL AND METHODS: 48 neuromas were treated surgically between 1979 and 1990.
      That represents 46 feet in 43 patients. Female predominance was clear with an
      average age of 53 years. The follow-up period was 6 years and 10 months. 3
      patients had multiple injuries. Medical treatment had been prescribed prior to
      surgery in 24 patients (15 had injections, 9 orthopedic shoe inserts and 5 both
      injections and inserts). The interval between the first symptoms and surgery was
      long since it was on average of 3 years and 6 months. The neuroma was located 36
      times in the third interdigital space. The initial incision was plantar 11 times
      dorsal 32 times. Only neurectomies were performed. The neuroma was very large 9
      times. 10 patients had treatment for other affections in the same operative time.
      RESULTS: At review, 41 feet were completely painless. Shoe wear was normal for 32
      patients. 12 pulpar hypoesthesia and 7 commissural and pulpary hypoesthesia were
      noted. 3 of 11 patients operated by the plantar approach had a painful
      hyperkeratosic scar. DISCUSSION: None of our cases had preoperative MRI because
      our most recent case has 4 years of evaluation. At the present time the MRI could
      contribute to diagnosis owing to good tissular differentiation. The neurectomy
      led to a total disappearance of pain but hypoesthesia was frequent. The dorsal
      approach induces cutaneous complication. Neurolysis induces a sensitive
      postoperative deficit but recurrence occurs in 77 per cent of cases after
      neurolysis. CONCLUSION: Morton's neuroma is located essentially in the third
      interdigital space. Neurectomy is a simple operation that often leads to
      recovery.

PMID- 7569191
TI  - [External fixation in fractures of the lower limb in children].
AB  - PURPOSE OF THE STUDY: The indications, morbidity and results of the use of
      external fixation for fractures of the lower limbs in children is presented.
      MATERIAL AND METHOD: We studied 72 fractures of the lower limbs (femur: 25;
      tibia: 47) in 63 children over a seventeen year period. Average age at fracture
      was 10 yrs 6 mos. (range 4 yrs 5 mos to 14 yrs 6 mos). Forty fractures were open
      fractures. The indication for external fixation was decided in three different
      situations: 39 isolated fractures, 11 patients with multiple fractures, and 13
      polytraumatized patients. Three different devices were used: Illizarov: 4, Judet:
      16, Orthofix: 52. The fixators were left in place until fracture union was
      demonstrable. RESULTS: Final results were classed into three groups: good, good
      following reoperation and sequelae. Comparison of the three different series was
      made using Student's T test. 9 axial deviations or malrotations occurred: 6 times
      correction was possible with the device in place. Three cases of osteomyelitis
      occurred at the fracture site. 23 pin tract infections occurred (23 per cent) 5
      of which were persistent and 4 required reoperation. The average healing time was
      different in the three groups: 4.5 mos for isolated fractures: 8.1 mos for
      multiple fractures and 5.7 mos for polytraumatized patients. Reoperation was
      required for 4 patients: 2 bone grafts, 1 decortication, 1 bone transport. Ten
      refractures occurred following removal of the device, 8 times in patients
      presenting multiple injuries. In 46 patients with a follow-up greater than 18
      months, 9 presented an overgrowth between 1 and 2 cm. Following an average follow
      up of 2 years 4 months, 7 patients presented sequelae, 56 had good results, 18
      following reoperation. DISCUSSION: The use of external fixation remains an
      irreplaceable method for osteosynthesis of open fractures with severe soft tissue
      injuries, multiple fractures or in the polytraumatized patient. Some
      disadvantages such as pin tract infections and refracture following device
      removal should be taken into consideration before using it for the treatment of
      simple, isolated closed fractures of the lower limbs in children. CONCLUSION:
      When external fixation is chosen for treating fractures, it is preferable to use
      a modular device which allows axial corrections. Local pin site care is essential
      to prevent early infection. Early weight bearing and dynamization as soon as
      possible will promote callus mineralization, removal of the device must be
      progressive and cast protection is recommended.

PMID- 7569193
TI  - [Surgical treatment of the rupture of the inferior tendon of the biceps. Apropos
      of 6 cases].
AB  - INTRODUCTION: The purpose of this study is to compare the results of direct
      reinsertion of the distal bicipital tendon to the bicipital tuberosity, with
      other methods described in the literature. MATERIAL AND METHOD: This study is
      based on six athletic patients, all male, ranging in age from 42 to 62 years old.
      The rupture of the biceps occurred during an unusually violent effort in flexion
      and forced supination of the arm at a 90 degree of flexion. The surgical
      procedure which took place between a week and a month after the accident,
      consisted in a direct reattachment of the detached tendon. RESULTS: No paralysis
      in the area of the radial nerve occurred. All patients regained normal range of
      motion of the joints with maintained strength. DISCUSSION: Faced with a recent
      lesion in a young patient, a reinsertion on the bicipital tuberosity is desirable
      in order to maximize the strength and movement of the biceps. This simple
      technique uses a single approach. It does not weaken the bicipital tuberosity nor
      the muscular function of the biceps.

PMID- 7569194
TI  - [Open post-traumatic anterior luxation of the hip in children. Apropos of a case
      and review of the literature].
AB  - INTRODUCTION: Anterior open traumatic dislocation of the hip in children is rare.
      MATERIALS AND METHODS: We report the case of a child aged 9 years, who presented
      following a motor vehicle accident an anterior open dislocation of the left hip
      associated with a fracture separation of the trochanter, a fracture of the
      homolateral humerus and a fracture of the contralateral femur. He was treated by
      open reduction of the dislocation and pinning of the various fractures. RESULTS:
      After 15 months functional result of the hip was good. The radiograms showed
      early signs of necrosis of the femoral head. DISCUSSION: The treatment consisted
      of emergency reduction of the dislocation. Despite this treatment, a review of
      the literature showed that necrosis of the femoral head is still frequent.
      CONCLUSION: Anterior open dislocation of the hip is a severe disease in the child
      and its prognosis becomes severe with the opening and the association with a
      fracture.

PMID- 7569192
TI  - [Rupture of the distal tendon of the biceps brachialis: apropos of 43 cases].
AB  - PURPOSE OF THE STUDY: Rupture of the distal tendon of the biceps is an uncommon
      occurrence. 43 cases were analyzed in a multicentric study in order to define
      etiological factors and treatment of this lesion. MATERIAL AND METHODS: 43 cases
      were reviewed from Fort de France, Paris, Marseille, Lyon and Suresnes. There
      were only male patients with an average age of 50 years. The mechanism of injury,
      the clinical and radiographic features, the anatomical findings and the results
      of surgical treatment were analyzed. 4 patients were treated conservatively and
      39 surgically. In 28 cases, anatomical reattachment of the tendon was performed.
      In 11 cases the tendon was simply attached to the brachialis anterior muscle.
      RESULTS: The mechanism of injury in all patients was passive extension against
      active flexion 17 patients had sustained injury while engaged in sports
      activities and 17 during domestic activities. Most of the patients were diagnosed
      clinically. Ultrasound and CT scan was useful in cases seen a long time after
      injury. In 34 cases avulsion of the bicipital tuberosity was found. Subjective
      results were good in 28 cases and poor in 5 cases. Objective testing was
      performed one year after injury using the criteria described by Baker: flexion
      and suppination force (maximum force) and endurance (ability to perform repeated
      contractions). Following attachment to the brachialis anterior, there was an
      average loss of 33 per cent of flexion strength and 52 per cent of supination
      strength. Following anatomical reattachment, the loss was 5 per cent for flexion
      and 15 per cent for supination. There were two cases of radial nerve palsies and
      1 case of radio-ulnar synostosis. DISCUSSION: Attachment of the biceps brachialis
      tendon to the brachialis anterior muscle is unable to restore supination force.
      Complications only occur following anatomical reattachment. Radial nerve palsies
      can be avoided by using two separate incisions as described by Boyd. CONCLUSION:
      Surgical reinsertion onto the radial tuberosity restore more strength. Attachment
      to the brachialis muscle can be sued in cases seen a long time after injury.

PMID- 7569195
TI  - [Femoral loosening of total hip prosthesis caused by pseudarthrosis resulting
      from trochanterotomy].
AB  - PURPOSE OF THE STUDY: This survey of 48 cases of trochanteric non-union in THR
      showed that this complication had not only functional consequences (one patient
      out of three complains of some instability and mild pain) but may also lead to
      stem loosening (3/48) through an original mechanism. The movements of the
      trochanter produce wear debris, mainly from the broken metal wires fixing the
      trochanter (and from rubbing of the cement on the femoral side of the osteotomy).
      These debris create an osteolytic granuloma between the proximal lateral
      endocortex and the cement, which extends progressively to the distal tip of the
      stem. MATERIAL AND METHODS: A continuous series of 446 cemented Charnley type
      prostheses by the trans trochanteric approach showed 48 trochanteric non unions
      (11 per cent) which were examined at an average follow up of 6.5 years. Six
      patients were reoperated for important hip instability. Ten who suffered only
      from moderate instability were not reoperated on. 32 were asymptomatic and
      therefore where not reoperated, but 3 of them suffered from severe femoral
      loosening after 6 years and required revision. RESULTS: These cases of loosening
      due to trochanteric non union were characterized by: clinical patterns: they
      occurred only after 6 years, in active patients under 50; radiological aspects:
      osteolysis was initially limited to the lateral cortex (without any calcar
      resorption or radio lucency around the cup) analysis by electronic microscopy of
      the granuloma (harvested at revision) showed metallic debris (under 1 mu) inside
      macrophages, with some cement particles (secondary to the loosening). DISCUSSION:
      Mechanism of loosening These cases of loosening differ from those due to
      granuloma caused by wear debris of PE and from granulomas resulting from
      deterioration of the cement around the femoral stem, which both occur only much
      later with the Charnley prostheses. In our consecutive series of 32 cases of
      Charnley THR in young active patients with an average follow up of 9.5 years, the
      only cases of femoral loosening observed were related to trochanteric non unions.
      Hyposolicitation by trochanteric non union does not lead either to bone
      resorption or to stem loosening, as we could notice in a series of moderately
      active patients over 60 with loose non unions. Loosening due to trochanteric non
      unions was only observed in active patients with tight non unions, as the
      patient's activity and contact of the surfaces increase rubbing and wear of metal
      wires. Prevention of trochanteric non union. Despite attentive care to fixation
      of trochanter there is an unavoidable percentage of non union even in simple
      cases (3 to 4 per cent according to Charnley). Therefore we advocate this
      technique only when a large exposition is necessary (revisions, THR for
      dislocation etc..) CONCLUSIONS: Trochanteric non union may lead to stem loosening
      after 6 years in active patients under 50. Therefore we recommend: to restrict
      the use of the trochanteric approach to some difficult THR: revisions, prostheses
      for dislocation, etc... to reoperate patients under 50 with a trochanteric non
      union: if it is clinically symptomatic if a progressive granuloma of the lateral
      cortex, even though asymptomatic, appears.

PMID- 7569196
TI  - [Growth hormone and the severely burnt patient].

PMID- 7569199
TI  - [Clinical and serological manifestations of 307 Spanish patients with systemic
      lupus erythematosus. Comparison with other ethnic groups].
AB  - There is evidence suggesting that clinical manifestations and severity in
      systemic lupus erythematosus (SLE) are associated with age, sex and ethnicity.
      The influence of genetic factors, particularly HLA antigens, on disease
      expression is revealed by the diversity of clinical conditions in patients from
      different ethnic groups. The aim of this work was to analyze the impact of
      demographic factors on SLE expression in the Spanish population. Therefore, a
      retrospective analysis was undertaken of clinical records of 307 patients
      diagnosed in three Rheumatology Services, with a mean follow-up of 79 months. The
      distribution of clinical manifestations according to age and sex was studied and
      compared with those observed in other ethnic groups. The results show the
      influence of sex and age on our patient population. Thus, female had a higher
      frequency of malar rash, photosensitivity and lymphopenia. Males had a higher CNS
      and renal involvement. Patients under 15 years had a higher involvement of CNS
      and kidney. Patients under 15 years had a higher frequency of nephropathy,
      hematological, cutaneous and CNS changes. Patients older than 50 had a higher
      frequency of pleuropericarditis, but without renal involvement. Our ethnic group
      expressed a disease with a severity similar to that observed in north-european
      caucasians, higher than in north-american caucasians and lower than in south
      american caucasians, asiatic and africans. In conclusion, patients with SLE from
      the south-european ethnic groups express a clinical picture with characteristics
      and severity similar to those observed in europeans from other latitudes and
      different from those reported in other ethnic groups.

PMID- 7569197
TI  - [Treatment of the diffuse and focal proliferative forms of lupus nephropathy with
      intravenous cyclophosphamide. Intravenous cyclophosphamide in systemic lupus
      erythematosus].
AB  - The objective is to evaluate the therapeutic effect and toxicity of IV
      Cyclophosphamide on the evolution of diffuse and focal proliferative forms of
      lupus nephritis. It's a prospective, descriptive and non-controlled study. We
      treated 12 patients (M/F = 1:11, aged 30.07 +/- 14.15) diagnosed by renal biopsy
      with diffuse proliferative (n = 10) and focal (n = 2) lupus nephritis. All
      patients received IV Cyclophosphamide. A dose of 1 g/sg.m of body surface area
      was administered monthly for the first three months and each three months until
      two years. The follow-up was 34 +/- 24.83 months (range 6-67). Seven patients
      completed two years of treatment with Cyclophosphamide with a further follow-up
      of 18.71 +/- 12.36 months (range 6-67). Renal function either improved or
      remained unchanged. Proteinuria, hematuria and immunologic markers decreased or
      normalized at three years. The patients who finished the period of two years with
      CFIV remained stable. There were neither infections nor hemorrhagic cystitis. We
      conclude that with the scheme of CFIV used by us good therapeutics effects will
      be obtained with minimum secondary toxicity in a follow-up of three to five
      years.

PMID- 7569200
TI  - [Bacteremia caused by group A and B beta-hemolytic Streptococcus in adults].
AB  - In order to know the epidemiological, clinical and evolutive characteristics of
      bacteriemia caused by beta-hemolytic streptococci groups A and B, a retrospective
      investigation was undertaken of 48 bacteremic episodes observed in adult patients
      for 10 years (1985-1994). Twenty-two episodes were caused by Group A beta
      hemolytic streptococci (GAS) and 26 by Group B beta-hemolytic streptococci (GBS).
      Patients with GAS bacteremia (GASB) had a lower mean age than patients with GBS
      bacteremia (GBSB) (p = 0.03). Infection with immunodeficiency virus was more
      common in patients with GASB than in patients with GBSBA (27 and 4%,
      respectively; p = 0.04); in contrast, diabetes mellitus was more common in
      patients with GBSB than in patients with GASB (27 and 5%, respectively) (p =
      0.04). Nine (41%) patients with GBSB were i.v. drug abusers; nevertheless, none
      of the subjects with GBSB were i.v. drug abusers (p < 0.001). The proportion of
      bacteremia without demonstrable source due to GBS (41%) was significantly higher
      than that due to GAS (9%) (p = 0.02). Five (23%) patients with GASB and other
      five (20%) patients with GBSB had fatal outcomes, but only in two (9%) and three
      (12%) cases, respectively, was death directly attributed to bacteremia. In
      conclusion, bacteremias caused by GAS and GBS have different epidemiological
      characteristics but similar prognosis.

PMID- 7569198
TI  - [Herpes-zoster virus infection in patients with systemic lupus erythematosus].
AB  - The prevalence of infection with VZV in 145 patients with SLE was investigated,
      with a mean follow-up of 7.6 years; its relationship with different variables,
      particularly with therapy of the underlying disease, was analyzed. Twenty
      episodes of VZV infection in 19 patients were diagnosed (13.1%). In no case was
      the therapeutic regime changed nor was worsening of SLE observed. There was
      neither dissemination of herpes nor superinfection. An increase in the number of
      VZV infections was observed in patients with SLE under corticosteroid therapy (p
      = 0.04) and particularly when drug administration was on a daily basis (p =
      0.00006). Cytotoxic agents also favored the infection (p = 0.0014). VZV infection
      is of a benign nature in SLE and its emergence is favored by immunosuppressive
      agents. The risk is lower if corticosteroid administration is on alternate days.
      There is no need to decrease therapy for SLE.

PMID- 7569201
TI  - [Extrapulmonary tuberculosis. Experience at a general hospital (1980-1993)].
AB  - In order to know extrapulmonary tuberculosis in our environment the results of
      all samples submitted for culture of mycobacteria to the Microbiology Department,
      Fundacion Jimenez Diaz, from 1980 to 1993 were analyzed. During this period 290
      cases of extrapulmonary cases were diagnosed, 101 from 1980 to 1985 and 189 from
      1986 to 1993. The most common site of infection before 1985 was in genitourinary
      tract (42.6%); in contrast, from 1986 onwards the more common sites of infection
      were pleural (22.8%), genitourinary tract and lymphatic glands (22.2% in both
      sites). When EPT was compared in the two periods of time the observations made
      were a relative decrease of genitourinary infections (p = 0.00004) and increase
      in disseminated (p = 0.015) and pleural tuberculosis (p = 0.011) from 1986
      compared with previous years. From 1986 a greater proportion of disseminated form
      was observed (p < 0.0001) in positive-HIV patients and of genitourinary (p =
      0.011) and pleural (p = 0.076) forms in negative HIV-patients. In conclusion,
      extrapulmonary tuberculosis has increased in our environment during the period
      1980-1993, and this increase is not attributable only to positive-HIV patients.
      The distribution of clinical forms of this disease was different in the two
      studied periods and among positive and negative HIV patients.

PMID- 7569202
TI  - [Lichen planus and hepatitis C virus infection. Study of 6 cases].
AB  - Lichen planus is an inflammatory dermatosis that has been associated to different
      chronic hepatopaties with a variable frequency. In recent years several case
      reports have been published dealing with lichen planus and its association to
      hepatitis C virus infection. We report six patients with lichen planus (four
      males, two females; aged 30-75) who also suffered a chronic hepatitis C virus
      infection. Lichen planus was confirmed by biopsy and viral infection was based on
      ELISA and RIBA-4 tests in all patients and also on PCR in five of them. A patient
      had also been diagnosed of porphyria cutanea tarda. Two patients were treated
      with alfa-Interferon. It did not modify the evolution of their lichen planus. We
      recommend to search for hepatitis C virus infection in lichen planus patients and
      also look for lichen planus patients suffering of chronic hepatopathies to
      improve our knowledge of the possible relation between both diseases.

PMID- 7569203
TI  - [Diagnosis in rheumatology; advantages and limitations of diagnostic criteria].
AB  - A review was made of advantages and limitations of diagnostic criteria for
      rheumatic diseases. Most criteria have been elaborated for unifying
      investigations and reports, although they are often used for diagnosis in
      individual patients, in clinical sessions or in medical reports. Classification
      criteria are not synonymous of diagnostic criteria. In medical terms, that a
      patient meets several classification criteria does not always have the same
      relevance as diagnostic criteria, but they may serve as initial guidelines for
      the examination of a given patient.

PMID- 7569204
TI  - [Non-rheumatic atrial fibrillation and antithrombotic treatment: current status].

PMID- 7569206
TI  - [21-hydroxylase deficiency. Review of the biochemical characteristics and their
      diagnostic implications].

PMID- 7569207
TI  - [Prognostic factors in systemic lupus erythematosus: their relationship with the
      choice of treatment].

PMID- 7569208
TI  - [Young woman with cutaneous lupus and lung effusion].

PMID- 7569205
TI  - [Current status of the regional treatment of hepatic metastasis from colorectal
      carcinoma].

PMID- 7569209
TI  - [Skin lesions with centrifugal growth].

PMID- 7569210
TI  - [Sinking of the craneal vault and headache].

PMID- 7569212
TI  - [Alveolitis and Pneumocystis carinii infection in a worker exposed to plaster].

PMID- 7569211
TI  - [Recurrent subcutaneous tumors in a woman from Equatorial Guinea].

PMID- 7569215
TI  - [Infant mortality and activities of the health care system from 1988-1992. Chiqui
      Gomez health area].
AB  - A study on infant mortality was carried out in the Chiqui Gomez health area of
      Santa Clara City during a 5-year period (1988-1992). Data were collected from the
      Statistics Department; analyses of familial health records; medical micro
      histories of pregnant women in family doctors' home offices; and from the
      supervision report of the Basic Work Group; diagnostic health status of the area
      was also taken into account. The method employed was descriptive and analytic.
      The study is concluded with the evaluation of the fulfillment of the Maternal
      Child Program as satisfactory in this health area. Causes of death in the first
      place were main perinatal disorders and congenital anomalies. Factors having a
      higher incidence in infant mortality in the study are; short intergenesic period;
      delivery before the 37th week of pregnancy; pregnancy in adolescence; and low
      birth weight. There is an evident relationship between pregnancy in adolescence
      and low birth weight; the results attained in prenatal care and infant care prior
      to children's death are considered adequate.

PMID- 7569213
TI  - [Visceral leishmaniasis in a patient with HIV-2 infection].

PMID- 7569214
TI  - [Lichen sclerosus and atrophicus and autoimmunity].

PMID- 7569217
TI  - [Night work and nurses health].
AB  - A case study was carried out in a hospital to determine differences in health
      status, working environment, and spare-time activities among a group of nurses
      doing day and night shifts. 25% of the night shift nurses were selected for the
      study; an equal number of nurses of the same hospital who did not do night shifts
      were taken as controls. Health disorders due to night-shift working conditions as
      well as aspects that may or not influence personal satisfaction in this working
      activity are indicated.

PMID- 7569216
TI  - [Development of low birth weight infants during the period from June 1988 to May
      1989 in the municipality of Abreus].
AB  - Due to the importance of the study of the pondostatural development of low birth
      weight infants, a research was carried out in the Abreus Municipality between
      June 1988 and May 1989. A survey was made to mothers of all low birth weight
      infants and medical histories were reviewed to assess the nutritional status and
      growth development of the infants in their first year of life; health problems
      during the infant period were taken into account as well as the following
      variables: sex, place of residence, number of times they had been hospitalized,
      and visits to outpatient services in the area due to health disorders. Children
      considered low birth weight infants (under 2,500 g) were the study universe;
      weight, height, and nutritional status were compared according to Cuban
      standards. The degree of development attained in our health area, as well as the
      efficient medical care given there were determined.

PMID- 7569219
TI  - [Nursing research on epidural analgesia for chronic cancer pain].
AB  - A retrospective study was made on 9 cases with pains due to advanced head and
      neck cancer, attended to at the Pain Clinic of the National Institute of Oncology
      and Radiobiology between 1988 and 1991. An epidural catheter was implanted to
      these patients at the CNS level for the administration of a morphine solution. 7
      patients (77.8%) showed total pain relief; and 2 cases showed easily-controlled
      slight pains. The most frequent complications were; fever (3 cases) and
      alterations of the level of consciousness (2 cases). No infections were reported.
      The importance of an adequate preparation of the patient and a strict follow up,
      where oncology nursing personnel play an important role, is pointed out.

PMID- 7569218
TI  - [Rise in knowledge and contact with drugs in 1st grade students of public and
      private schools in Ribeirao Preto].
AB  - This study was made to determine contact with drugs among first-grade students
      from public and private schools in the Riberao Preto community. The various
      social classes were considered. We decided to use the concept of social status
      for out empiric research, which defines it as a group of persons who have a
      certain number of characteristics in common which can be measured, that is,
      common status, and which may be defined by different criteria. Schools were
      classified according to their pupils, and after this initial classification, they
      were divided into 4 groups. A school was selected by lots from each group. A
      questionnaire with open and closed questions was used as instrument for data
      collection. According to the collected data, it was concluded that all pupils,
      independently from their social and economic level, had a superficial knowledge
      on drugs: 48.2% of those surveyed said they knew people in their neighbourhood
      who used drugs; 8.8% referred that they had been offered drugs. Drugs offered to
      them included; cocaine, marijuana, hashish, cigarettes and toxic pencils. The
      other 63% referred that nobody had given them any advice regarding drugs.

PMID- 7569220
TI  - [Myocardial revascularization. Postoperative care by the intensive care nurse].
AB  - A retrospective and cross-sectional study was carried out on a total of 92
      patients admitted at the Intensive Care Unit of the Santiago de Cuba's Heart
      Center between April 1992 and June 1993, who underwent surgery for myocardial
      revascularization. We point out the skilled and dedicated attention of the
      intensive care nurse in the preparation of the patients, during the operation,
      and in the postoperative period, having a favorable influence on the general
      mortality which occurred only in 1.8%.

PMID- 7569221
TI  - [Nursing research on the rehabilitation of neurological and neurosurgical
      patients].
AB  - A descriptive study was carried out on the main aspects related to the
      rehabilitation of neurological and neurosurgical patients. A review was made on
      books, symposium papers and theses; specialists were also consulted. Several
      variables were studied, among them, basic objectives and purposes of the
      rehabilitation program; peculiarities of the patient's psychologic adaptation to
      physical disability; assessment of handicaps; and the nurse's role in
      rehabilitation.

PMID- 7569224
TI  - [Absence of interaction between Trypanosoma theileri infections with the
      diagnosis of animal trypanosomiasis by detection of circulating antigens].
AB  - This work presents data gathered at the CIRDES (Centre international de Recherche
      Developpement sur l'Elevage en Zone subhumide) during epidemiological monitoring.
      The prevalence levels of Trypanosoma vivax, Trypanosoma congolense and Trypansoma
      brucei obtained using antigen-detection ELISA were compared in non-infected
      animals and in animals infected with Trypanosoma theileri. The aim was to
      investigate whether there were any serological cross-reactions between T.
      theileri and the pathogenic trypanosomes. The results show that there was no
      interaction by Trypanosoma theileri with the diagnosis of the pathogenic
      trypanosomes using antigen-detection ELISA.

PMID- 7569223
TI  - [High serological prevalence of bovine anaplasmosis in North-Cameroon].
AB  - Between 1989 and 1994, cases of acute bovine anaplasmosis were rarely diagnosed
      in Northern Cameroon. However, the Becton-Dickinson anaplasmosis card test
      revealed high prevalence rates, especially in the North and Far North provinces.
      Bovine anaplasmosis might be clinically important in areas where the proportion
      of non-immune cattle is higher.

PMID- 7569225
TI  - [Comparison of the pathogenic effect in mice between stocks of Trypanosoma evansi
      from Mauritania and from Kenya, Niger, Chad and China].
AB  - The pathogenicity to mice of a stock of Trypanosoma evansi from Mauritania has
      been compared to that of stocks from Kenya, Niger, Chad and China, using doses of
      5.10(5), 2.10(6) and 5.10(6) trypanosomes per mouse. The survival of mice
      inoculated with stocks from Kenya, Niger and China is short, on average 2.1 to
      6.5 days. Mice inoculated with stocks from Mauritania and Chad survive longer,
      12.5 to 22.7 days, depending on the dose.

PMID- 7569222
TI  - [Use of computer simulation in the study of the nurse's attention to the family].
AB  - The purpose of this work was to show the results attained with the application of
      computer-assisted simulation in the teaching of the subject Familial Nursing
      Care. The study was carried out at the Julio Trigo Lopez Faculty of Medical
      Sciences during the second semester of the 1992-1993 school year. Work was based
      on 35 students of the fourth year of Nursing Degree. Six (6) computer-assisted
      simulations were elaborated and 2 instruments were created: Opinion Survey and
      Written Simulation. 82.4% of the students pointed out advantages in using the
      Simula software; 82,3% said that it improved their knowledge; and most students
      said that the Simula method was more useful for their final evaluation and had
      higher feedback.

PMID- 7569227
TI  - Continuing prevalence of African horse sickness in Nigeria.
AB  - Equine sera collected from 10 widely separated regions throughout Nigeria were
      tested for antibodies against African horse sickness viruses (AHSV) using a
      competitive enzyme-linked immunosorbent assay (ELISA). The animals sampled
      included imported, exotic horses, indigenous and locally cross-bred (local)
      horses and African donkeys. A high percentage of the sera (79.8%) were positive,
      confirming the continued prevalence of AHSV antibodies in Nigerian horses and
      donkeys.

PMID- 7569226
TI  - A survey of dermatophilosis in Israeli dairy cattle.
AB  - In Israel, dermatophilosis was found to inflict severe lesions, especially in
      first-calving cows during the first weeks post-parturition. Decreased milk
      production (by 40% on average) was also noted. Acute exudative dermatitis was
      observed in these animals. Severely reacting animals (570 in 38 kibbutz herds and
      15 animals in 4 family herds) were treated with antibiotics. All these animals
      also suffered either from endometritis/metritis or mastitis. The "tumoral" form
      of dermatophilosis was observed on 3-week-old or younger calves. Dermatophilosis
      was especially prevalent (89.4%) in dairy herds in which intensive showering of
      lactating cows is practised during the spring and summer months, in comparison to
      the family herds where the morbidity rate was lower (6.6%). Morbidity rates were
      found to be higher in the humid Mediterranean Coastal Plain (66.3%) than in the
      arid or semi-arid regions (Negev and Arava Valley) of Southern Israel (3.7%).
      Five clinical forms of dermatophilosis and the epizootiological aspects of the
      disease in Israeli dairy herds are described. It is concluded that a reduction in
      the prevalence of dermatophilosis could be achieved by decreasing the frequency
      and the intensity of showering currently applied under the kibbutz management
      system.

PMID- 7569229
TI  - [Use of the B19 strain in the prevention of bovine brucellosis in northern
      Cameroon. Study of effect of the dose on seroconversion rate and duration in
      female zebu].
AB  - Four herds of zebus from northern Cameroon totalling 136 animals were vaccinated
      subcutaneously with the following doses of Brucella abortus strain 19: 5 x 10(9)
      colony-forming units (CFU), 10(9) CFU, 5 x 10(8) CFU and 10(7) CFU. Twenty-eight
      days after vaccination, the following seroconversion rates were observed
      respectively: 97.4, 96.2 84.2 and 73.3%. Of the 52 animals which could be tested
      subsequently including 39 over one year old on the vaccination day, only one
      showed antibodies 6 months after vaccination. The cost price of the strain 19
      vaccine produced at the Bokle National Veterinary Laboratory was estimated to be
      65 F CFA at the 10(9) CFU dose and 1,740 F CFA at the 5 x 10(10) CFU dose usually
      recommended. The use of the Buck 19 strain in the medical prophylaxis of bovine
      brucellosis in northern Cameroon is discussed.

PMID- 7569230
TI  - Comparison of two anticoagulants for production of antigens of Cowdria
      ruminantium in neutrophils.
AB  - Ethylene diamine tetra-acetate (EDTA) and lithium heparin were used comparatively
      as anticoagulants for blood obtained from goats clinically infected with Cowdria
      ruminantium. Neutrophils were extracted from the blood and cultured for the
      production of heartwater antigen. EDTA proved superior to heparin in terms of the
      recovery rate and the better separation of neutrophils from other leucocytes. The
      antigen produced was tested in the indirect fluorescent antibody test (IFAT) and
      proved to be of good quality. Production of antigen slides by this method is
      recommended for moderately well-equipped laboratories in heartwater-endemic
      areas.

PMID- 7569231
TI  - The serological response to heartwater immunization in cattle is an indicator of
      protective immunity.
AB  - A significant correlation was demonstrated in Friesian-cross steers between the
      serological response to previous vaccination with the Ball 3 strain of Cowdria
      ruminantium and the development of protective immunity against the Kalota isolate
      from Malawi. Of 10 animals which seroconverted after vaccination, all were
      completely or partially immune to challenge. Ten of the 14 animals which failed
      to seroconvert were immune but the proportion was not significantly different
      from that in the unvaccinated controls (4/10). Of 29 animals vaccinated and
      treated simultaneously with a slow-release doxycycline implant, 13 failed to
      seroconvert, and of these, four were completely susceptible to challenge.

PMID- 7569228
TI  - Effect of three different routes of administration on the immunogenicity of
      infectious bursal disease vaccine.
AB  - The immune response of three groups of 10 chicks, vaccinated at age of 2 weeks
      against infectious bursal disease (Gumboro disease) via the oral, intramuscular
      and ocular routes, is compared. The vaccine was prepared by the NVRI (Vom,
      Nigeria). All chicks in the three groups remained seronegative 3 weeks after
      primary vaccination. However, precipitating antibodies were present in birds
      which received a booster dose at the age of 6 weeks. Post-vaccination
      seroconversion was observed at the age of 6 weeks in 70% of the birds vaccinated
      via the ocular route. This rate increased to 80% during the two following weeks
      and then decreased to 55.6% until the 10th week. In the groups vaccinated by the
      oral and intramuscular routes, the seroconversion rate in the 7th week was 30 and
      33.3%, respectively, but increased to 87.5% in both groups at the end of the 10th
      week. Considering the age factor in the susceptibility of chicks to infectious
      bursal disease, the authors recommend the ocular route as the most effective for
      vaccination.

PMID- 7569232
TI  - [Foot-and-mouth disease in Southeastern Asia. Situation and control planning].

PMID- 7569234
TI  - [Nursing education: in search of autonomy].

PMID- 7569233
TI  - [Psychosocial analysis of the health-disease process].
AB  - This article is a reflection about the transdisciplinary paradigmas of the health
      illness process noting the symbolic mediation between the reactions of the
      biological organism and the socio-environment factors including the pathogenic
      ones. The symbolic-affective mediation is analyzed from the perspective of Social
      Representation theory allowing one to comprehend the references of individual and
      collective actions in the health-illness process.

PMID- 7569235
TI  - [Experiences with the use of nursing models in research].

PMID- 7569236
TI  - [The importance of administration applied to nursing practice according to the
      opinions of nursing graduates].
AB  - The objective of this study was to know the opinions that the students have, when
      they begin the course of Administration applied of Nursing. The results indicated
      that the students considered administration a manner how the nurses are
      organizing their works and that nursing activity administration is to conciliate
      the assistance with the bureaucratic service.

PMID- 7569237
TI  - [Development of data bases for various nursing activities].
AB  - The purpose of this study is to discuss the utilization of informatics in nursing
      and the construction of computerized data bases by nursing professionals that
      have no previous experience with computers. Three data bases developed during the
      pos graduate nursing course are described.

PMID- 7569239
TI  - [Influence of the dominant ideology on the position of nursing students
      concerning abortion].
AB  - A new prism is used to re-analyse the results of two investigations developed by
      the authors with nursing students, concerning their position about the abortion.
      As they discuss the questions and the limits of the previous investigation
      methodology, they also show the relevance of an expanded understanding of the
      theme, through its articulation with the dominant ideology.

PMID- 7569240
TI  - [Data collection in nursing: report of a teaching experience].
AB  - After courses of Assessment of Adults questionnaires were sent to 84 nurses in
      order to know if their practice of physical examination was modified by them.
      These nurses worked in different hospitals and graduated schools. The majority of
      them related that they improved their knowledge about the matter and modified
      their practice.

PMID- 7569241
TI  - [How I managed peristomal dermatitis].
AB  - Peristomal skin irritation is one of the most frequent complication in the
      ostomate's rehabilitation process. It can and must be avoid through a specialized
      care. The author makes a literature revision and approaches the causative and
      associated factors to the skin damage, its classification and the preventive and
      therapeutical principles in Nursing Stomal therapy.

PMID- 7569242
TI  - [Nutrition evaluation of female university students].
AB  - The self-evaluation of nutritional status, utilized as a teaching strategy of
      introductory nutrition course at Nursing School (Sao Paulo's University), gave a
      subsidy to this work. With this purpose, 50 female university students
      3rd'semester (mean age was 21.7) were required to complete a three days food
      record and report their approximate height and weight. The analysis of food
      intake adequacy indicated that 98% of the students had insufficient intake (less
      than 90% of recommended of National Research Council-1980) of, at least, one of
      the nutrients (protein, calcium, iron, vitamin A, B1, B2, C and niacin). It was
      evidenced an inadequate intake (less than 90% of RDA) of calcium (80% of the
      students), vitamin A (72%), iron (64%), vitamin B1 (74%), vitamin B2 (56%) and
      vitamin C (34%). The inadequate intake was more frequently and serious (less than
      60% RDA) for calcium (42%), vitamin A (20%) and iron (16%) showing a vitamins and
      minerals deficient diet.

PMID- 7569243
TI  - [Relationship between the aged and their families].
AB  - This paper is an explorative--descriptive study trying to reach the following
      objectives: to know the interpersonal relationship between the elder and his
      relatives and verify what is the elder's perception about the elderly process.
      The authors interviewed 20 persons (10 men and 10 women) after 60 years of age.
      The results showed probably will give some guidance for the nursing assistance to
      the elderly population.

PMID- 7569244
TI  - [When practice approaches theory].

PMID- 7569246
TI  - [Afro-Brazilian religions: an aid in the study of spiritual distress].
AB  - This paper discusses the Afro-Brazilian religions (candomble, umbanda, quimbanda,
      muslim, and vodum) and points out the issues related to the spiritual distress as
      a nursing diagnosis.

PMID- 7569238
TI  - [Patient classification systems. Costs of nursing].
AB  - Determining the cost of providing nursing care to hospital patients is a major
      concern for nursing administrators, especially in developed countries. It is
      stressed that the costing-out of nursing service is generally viewed as
      advantageous for the nursing profession. Three basic methods for allocating
      hospital nursing service costs are described. The first is a per day service
      method (per diem) that relates nursing costs directly to length of stay. The
      second method, the relative intensity measures, tries to relate patient's
      condition (use) of nursing resources to his medical condition. The third
      alternative to costing nursing is based on patient classification system, which
      measure patient requirements or nursing workload.

PMID- 7569247
TI  - [Decreased demand for nursing courses--a profile of the profession among young
      people].
AB  - This study, which is based in a descriptive exploratory charter objectified to
      identify the perception that young people have concerning to the factors which
      possibly have been influencing the process of how to choose a professional career
      for nursing, been possibly to identify an outline for nursing. Outline, is not so
      attractive for the young people to select this profession.

PMID- 7569248
TI  - [The significance of nursing administration as seen by graduates. II].
AB  - The objective of this study was to know the opinions about the significance, felt
      by the students of the Nursing School of the University of Sao Paulo, at the end
      of the theoretical part of the course of administration applied to nursing
      practice. Therefore the opinion of 30 students at 8th semester of the Nursing
      School has been collected. The results demonstrated that the students understood,
      the administration applied to nursing practice, as an instrument for the nurses
      work and to increase the quality of assistance, as well as for the development of
      the nursing staff and, the administrative functions as a role which has to be
      developed in the nursing professional practice.

PMID- 7569249
TI  - [The physical assessment and the intensive care unit nurse].
AB  - The goal of this study was to analyse some practicing, teaching and learning
      aspects of physical examination done by ICU's nurses. It was accomplished with 26
      ICU nurses that concluded the Intensive Care Nursing Specialization Course at the
      School of Nursing at Sao Paulo University. The results showed that 31 (68.9%) of
      the 45 presented items were done frequently by more than 50% of the nurses. The
      professional practice was considered the most important moment to physical
      examination learning. The responsibility by teaching was attributed to
      undergraduation course by 69.2% of the nurses.

PMID- 7569245
TI  - [Systematization of high-risk pregnancy care: a strategy for teaching obstetric
      nursing].
AB  - The present study describes a teaching experience using high risk pregnancy
      nursing care systematization with patients of a maternity. It also shows the
      students opinion of the use of such methodology.

PMID- 7569250
TI  - [Rogers' science of Unitary Human Beings and her views on creativity in nursing
      practice].
AB  - The article describes some of the uses and conceptualizations about creativity in
      nursing by the point of view of Martha Rogers. Rogers' Science of Unitary Human
      Beings considers the use of nurses' creative potential as something to develop
      nursing knowledge and practice.

PMID- 7569251
TI  - [The trash collection service: occupational risks versus damages to health].
AB  - The authors studied the kind of work a sample of 36 garbage collectors have been
      doing in a city of the State of Sao Paulo. A high frequency of occupational
      accidents and sick-due to health problem and some occupational risks was observed
      among them, and also that these worker haven't worn the individual protection
      equipment received, that probably contributes to such number of stop working.

PMID- 7569252
TI  - [Nurses specialized in neuroscience. A necessity?].
AB  - A specialization in nursing seems to be a preoccupation of several professional
      as a means to improve the professional practical. Specifically, the neuroscience
      nursing expression makes thought in a possible area which the nurses could
      develop and specialize themselves. The present report shows some enlightenment on
      what neuroscience nursing is, the actuation possibilities for the nurses and what
      could be developed in a specialization course, based in american literature.

PMID- 7569253
TI  - [Teaching communication in the nursing graduation course at the nursing school of
      the Minas Gerais Federal University].
AB  - Facing the importance of the communication in all nursing activities, in this
      paper the authors try to verify how has been occurring the teaching-learning
      process related to the communication subject during the undergraduate nursing
      course in the Nursing School at Federal University of Minas Gerais. The data were
      collected by interviewing professors and students from the undergraduate course.
      The results showed that the basic problem in this process is not "what" to teach
      but "how" to teach the subject.

PMID- 7569254
TI  - [Breast self-examination: identification of factors that may influence its
      practice].
AB  - The aim of this study was to identify the factors that influences the practice of
      breast self-examination (BSE) by nursing teachers. Seventy professionals were
      interviewed. Although all of them judged important the realization of the BSE,
      20% didn't practice it. The identified factors were: the technical knowledge
      concerning breast cancer, the desire of early detection of possible alterations
      (80%), the lack of ability to identify those alterations, the fear of discovering
      some alterations and also negligence, possibly influenced by their beliefs and
      values about health.

PMID- 7569256
TI  - [Epidemiology: an instrument for the nurse's working process?].
AB  - This paper discusses the role of the epidemiology in the nurse's work process. It
      searches for the comprehension of the work process's concepts and their elements
      deriving from a marxist analysis. It discusses the importance of this
      comprehension for the knowledge/recognition of the nursing profession and the
      epidemiologic support question as a work instrument.

PMID- 7569255
TI  - [Advantages of nursing laboratory teaching].
AB  - Reviewing the literature, the author describes some advantages of the psychomotor
      skill teaching at nursing laboratory as a previous training to the clinical
      service setting. The arguments herein presented are related, first to the ethics
      (questioning the mistakes made by the trainee on the patient); second, to the
      psychological nature by pointing out the trainee, the patient and the teacher's
      conflicts, as well as aspects on the cost-benefit obtained with this preliminary
      training; and third, to the pedagogy. These last mentioned aspects are supported
      on the psychomotor learning theories which confirm the importance of a nursing
      laboratory.

PMID- 7569257
TI  - [Therapeutic options in cardiogenic shock].
AB  - Cardiogenic shock continues to be a clinical situation which is related with high
      mortality. Although its etiology is varied, the most frequent cause is an acute
      myocardial infarction. The poor prognosis of cardiogenic shock can be favourably
      modified with the diagnosis of the underlying cause followed by the stabilization
      of the patient and early revascularization. Early treatment with inotropic or
      vasopressor drugs improves the condition of most patients and the use of
      circulatory assistance, such as the intraaortic balloon, lead to an acceptable
      hemodynamic situation in 80% of cases. However, they do not significantly modify
      the mortality rates. In addition, thrombolytic therapy does not appear to be
      effective for this kind of patients. Only revascularization methods have proved
      to be effective; surgery is the only option where ventricular septal, free wall,
      or papillary muscle rupture occurs, resulting in survival rates of between 50 and
      60% with coronary artery by-pass surgery. Angioplasty is frequently successful in
      reperfusion of the infarct-related artery; the survival rate in these cases is
      approximately 70%, according to the different series published. As the mortality
      rate is exceedingly high (70-90%) when conventional therapy is used; when
      appropriate diagnostic and therapeutic means are available and when the patient's
      condition is recoverable, the attitude should be aggressive and coronary
      angiography and angioplasty applied as soon as possible. In centers where these
      means are not available, once measures have been taken to achieve the
      stabilization of the patient, the most suitable procedure is to transfer him or
      her to a hospital in which qualified staff and such treatment methods are
      available.

PMID- 7569259
TI  - [Thrombolytic treatment in acute myocardial infarction in the aged: arguments in
      favor].

PMID- 7569258
TI  - [Thrombolytic treatment in acute myocardial infarction in the aged: arguments
      against].

PMID- 7569260
TI  - [Changes in lipoprotein(a) after heart transplantation].
AB  - AIM: The purpose of this study was to analyze the evolutionary changes of
      lipoprotein (a) levels occurring in heart transplant and to evaluate the possible
      relationship between the plasma concentration of this lipoprotein and the
      immunosuppressor drugs normally used in this type of transplant. METHOD: 17
      patients undergoing heart transplant and with no history of dyslipemia or
      dysglucemia were studied. Patients with metabolic alterations after the
      transplant were excluded (except when these alterations occurred during the first
      week), as well as those who showed intercurrent processes near to the
      determinations. These were performed before the transplant, and 1, 2, 4 and 6
      months later. RESULTS: An increase of lipoprotein (a) was observed after the
      transplant, with a subsequent progressive decrease. Significant differences were
      found between the levels prior to the transplant (9.18 +/- 8.66) and 6 months
      later (7.53 +/- 8.86), with no differences found between the previous
      concentrations and the determinations after one month (10.29 +/- 7.58), two
      months (8.06 +/- 7.90) and four months (8.82 +/- 7.84). Differences were also
      observed between the values of the first month in relation to the subsequent
      months, as well as between the 4th and the 6th month. No relationship was noticed
      between the levels of this lipoprotein and those of cyclosporin (r = 0.10),
      azatioprine (r = 0.17) and deflazacort (r = 0.19). CONCLUSIONS: The lipoprotein
      (a) levels increase after heart transplant, with a subsequent gradual decrease
      even below the previous figures. These levels bear no relationship with the dose
      of immunosupressors normally used in heart transplant.

PMID- 7569261
TI  - [ST segment elevation during exercise test and perfusion scintigraphy in patients
      without infarction].
AB  - BACKGROUND: The features of perfusion scintigraphy in patients who show exercise
      induced ST-segment elevation in the absence of previous infarction have been
      assessed in only a few reports. Therefore, we have evaluated our experience in a
      wide review of exercise 201-thallium scintigraphies. METHODS: 16,620 exercise 201
      thallium scintigraphies, carried out between 1986 and 1993, have been
      retrospectively reviewed. Fourteen patients (0.8/1000) without previous
      infarction who were evaluated for chest pain showed ST-segment elevation. In all
      patients coronary arteriography was also available. RESULTS: Five patients were
      free from significant coronary artery stenoses, 6 had one-vessel disease, 2 had
      two-vessel disease, and the remaining patient had three-vessel disease. In 8
      patients ST-segment elevation (up to 3-24 mm) was inferior, in 5 anterior and in
      1 lateral. The radionuclide was injected during ST-segment elevation in 10 cases
      and before such elevation (which developed in the postexercise phase) in 4. In 3
      out of these 4, which had angiographically normal coronary arteries, the
      scintigraphy was negative. In all cases where thallium-201 was injected during ST
      elevation, severe perfusion defects were detected corresponding to the
      localization of ST elevation. In the 4 patients with critical coronary stenoses,
      thallium-201 redistribution after 3 hours was partial. CONCLUSIONS: In patients
      without previous infarction and with exercise-induced ST-segment elevation, very
      severe perfusion defects are detected when the radionuclide has been injected
      during the crisis. Thallium-201 redistribution after 3 hours was not total in
      patients with fixed critical stenoses. When radionuclide injection preceded the
      crisis, the result of the scintigraphy was in agreement with the coronary
      anatomy.

PMID- 7569263
TI  - [The turn of the myocardium].

PMID- 7569262
TI  - [Echocardiography and MIBI-SPECT scintigraphy during dobutamine infusion in the
      diagnosis of coronary disease].
AB  - BACKGROUND AND PURPOSE: Dobutamine, an adrenergic agonist, has been combined with
      echocardiography and scintigraphy with MIBI-SPECT to detect coronary artery
      disease. Our purpose has been to compare echocardiography and MIBI-SPECT
      scintigraphy during dobutamine infusion for diagnosing coronary artery disease.
      METHODS: Both tests and coronary angiography have been performed on 72
      consecutive patients with chest pain and no previous history of coronary artery
      disease. Dobutamine had administered up to 40 micrograms/kg/min. Atropine was
      given when necessary. MIBI was injected at peak stress. Echocardiographic
      continuous monitoring and SPECT images were carried out. Positivity was defined
      as: 1) echocardiographic: wall motion abnormalities of new onset, and 2)
      scintigraphic: dobutamine-induced perfusion abnormalities. RESULTS: Coronary
      artery disease was demonstrated in 49 patients. Echocardiography was positive in
      37 of them (sensitivity of 75%) and MIBI-SPECT in 43 (sensitivity of 88%; p =
      NS). Specificity was higher with echocardiography (22/23, 96%) than with
      scintigraphy (16/23, 69%, p = 0.02). Accuracy was 82% for both tests. More
      patients with multivessel disease were detected by scintigraphy (61% versus 35%;
      p = 0.09). Agreement between tests was as follows: 1) results: 77% (kappa =
      0.53); 2) segments: 86% (kappa = 0.65), and 3) artery diseased: 90% (kappa =
      0.84). CONCLUSIONS: Echocardiography and MIBI-SPECT in combination with
      doubtamine are useful techniques to detect coronary artery disease. Diagnostic
      accuracy is similar with both tests.

PMID- 7569264
TI  - [Myocardial diseases: lessons from the past and future prospects].
AB  - This report provides an overview of current concepts on the cardiomyopathies.
      They constitute a heterogeneous group of diseases with complex interrelations
      between clinical manifestations, pathophysiology and therapy. Special emphasis
      was made to review new advances on the diagnosis and current management of
      patients with hypertrophic cardiomyopathy. The link between the classical
      knowledge and recent--still evolving--ideas is addressed to provide the--state of
      the art--concerning the implications on the clinical decision making process.
      Controversial issues such as diagnostic criteria, prognostic features and
      implications of electrocardiographic and echocardiographic data are revisited in
      brief. Data suggesting the value of dual chamber pacing as a means to relieve
      outflow tract obstruction and to improve symptoms in patients with hypertrophic
      cardiomyopathy are discussed. The molecular basis of this entity together with
      the characterization of the responsible genetic mutations are reviewed in detail.

PMID- 7569265
TI  - [Variant angina pectoris related to the treatment of migraine].
AB  - A 54 years-old man with a history of migraine, suffered from chest pain together
      with ST-segment elevation related to the intake of drugs against migraine
      attacks. The coronary arteriography showed normal coronary arteries. We suggest
      coronary artery spasm as the most probable cause of ischemia. We conclude that
      vasoactive drugs against migraine must be utilized with caution, or even avoided
      in patients with chest pain suggestive of myocardial ischemia.

PMID- 7569268
TI  - [Radiofrequency ablation of a posteroseptal accessory pathway associated with
      coronary sinus diverticulum].
AB  - The case of a patient with a symptomatic Wolff-Parkinson-White syndrome
      undergoing attempted radiofrequency catheter ablation of a posteroseptal
      accessory pathway is described. Coronary sinus venography revealed the presence
      of a diverticulum attaching near the os. The electrogram recorded from a catheter
      placed in the narrow neck of the diverticulum revealed a short atrioventricular
      time during sinus rhythm. The pathway was easily ablated using radiofrequency
      energy applied in the neck of the diverticulum, after multiple failed attempts at
      catheter ablation from the endocardial surface of the posteroseptal space. Our
      report emphasizes the importance of searching for a coronary venous diverticulum
      in all patients with posterior accessory pathways undergoing catheter ablation.

PMID- 7569267
TI  - [Aortic intramural hematoma. An atypical pattern equivalent to aortic
      dissection].
AB  - A case is presented of a hypertensive woman who had suffered a stabbing back pain
      for some three hours, with mild irradiation to precordium and accompanied by
      vegetative signs. A sinusal rhythm and negative T waves of little depth were seen
      on the ECG. A transthoracic bidimensional echocardiogram (TTE) showed a normal
      left ventricle with a somewhat dilated aortic root and the existence of a double
      echo running parallel to the anterior wall of the aorta but non-ondulating and
      without a visible intimal flap. Because of suspected aortic dissection an urgent
      contrasted CAT and a transesophageal echocardiogram were performed. These were
      informed as an aneurysm of the aortic root with mural thrombus from the ascending
      to descending aorta, but with no existing intimal flap suggesting dissection. A
      cardiac catheterization showed a mildly some dilated aortic root without
      dissection signs and normal left ventricle and coronary arteries. The patient was
      presented for surgical evaluation but, since no dissection was present, was not
      considered urgent surgery; she was admitted to the coronary unit and died 48
      hours later in a situation of acute pericardial tamponade, documented by TTE,
      surely due to rupture of the aortic root to pericardial sack. This way of
      presenting threatened aorta rupture that has been only recently recognized is
      discussed, as well as some misconceptions which must be avoided.

PMID- 7569266
TI  - [Syncope and chest pain. Demonstration of the mechanism by the hyperventilation
      test].
AB  - Two patients admitted to hospital because syncope and chest pain are presented.
      In both patients, hyperventilation test caused severe myocardial ischaemia (ST
      segment elevation) and sudden development of presyncopal sustained ventricular
      tachycardia which immediately responded to intravenous nitroglycerin. The
      relationship between coronary vasospasm and sudden death secondary to polymorphic
      ventricular tachycardia is discussed. Also, the usefulness of the
      hyperventilation test to detect this problem and to monitor its therapeutic
      response is addressed.

PMID- 7569269
TI  - [Limitation of atherosclerosis in coronary arteries with pravastatin (PLAC 1)].
AB  - PLAC 1 is a double-blind, randomized, placebo controlled trial assessing the
      efficacy of monotherapy with an HMG CoA reductase inhibitor (pravastatin) in
      altering the atherosclerotic process. This trial was an angiographic trial
      undertaken in the United States and was completed in early 1994. Despite the fact
      that angiographic end-points were the prime focus during the planning and
      execution of the trial, significant impact was seen in the area of clinical
      events, particularly fatal and nonfatal myocardial infarctions. The latter were
      significantly reduced in the treated patients. These results were paralleled by a
      significant slowing of progression in the treated patients. Importantly, the
      angiographic effects were predominant in prevention of new lesion formation and
      in slowing the progression of mild/moderate lesions less than 50% diameter
      stenosis at baseline. Current concepts suggest that the latter two categories of
      lesions are the most important in linking angiographic outcomes with clinical
      events. PLAC 1 is the first trial to concomitantly show statistically significant
      effects in clinical end points and angiographic end-points in the category of new
      and/or mild stenoses. These results are compatible with the concept of plaque
      stabilization.

PMID- 7569270
TI  - [Is there a relationship between cholesterol reduction, low levels of cholesterol
      and mortality?].
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- 7569272
TI  - [Why the cardiologists should be interested in lipids?].
AB  - This review discuss the possible 10 top reasons why cardiologists are/should be
      interested in lipids. 1. Epidemiologic evidence. Blood lipid levels are risk
      factors for coronary heart disease and predict subsequent mortality in the
      patients seen by cardiologists. 2. Lipids play a major physiopathologic role in
      ischemic heart disease. Stenosis of the coronary arteries are produced by
      atherosclerotic plaques, composed of a mass of lipids covered by a fibrous cap.
      Plaques with increased lipid content appear more prone to rupture and cause acute
      coronary syndromes. 3. Lipid abnormalities are very common in patients with
      ischemic heart disease. At least half the patients with angiographic evidence of
      significant coronary artery narrowings have severe abnormalities of lipids that
      are easy (and cheap) to detect. 4. Reduction of cholesterol is associated with
      regression of atherosclerosis, as has been demonstrated by angiography in
      patients with coronary heart disease. 5. Reduction of cholesterol is associated
      with reduction of symptoms and ischemic events. 6. The most striking benefit of
      lipid lowering therapy is shown in patients, already with evidence of ischemic
      heart disease. 7. The new lipid lowering agents present a new profile of actions
      and may improve symptoms in the short term. 8. There is still controversy about
      who should be treated, when and with what drugs, and this questions will be
      solved with the evidence of large, multicenter, well designed trials that are now
      in progress. Cardiologists must contribute to this studies, know and discuss the
      results. 9. If a patient is not given by his cardiologist any drug to reduce the
      cholesterol it is quite improbable that other doctor would make such
      recommendation. 10. Even if the cardiologist is not interested in lipids their
      patients are, and seek and deserve advice.

PMID- 7569271
TI  - [Reduction of coronary events: what are the possible mechanisms?].
AB  - Clinical studies have shown that lipid-lowering therapy reduces the incidence of
      cardiovascular events. However, lesion regression is relatively minor and does
      not seem to reflect the clear improvement in clinical events. Normalization of
      the lipid profile correlates with a reduction in atheromatous plaque
      complications. The responsible mechanisms for such reduction are diverse and are
      the subject of extensive research.

PMID- 7569275
TI  - Amniotic fluid phospholipids. New predictive values of L/S and PG/S ratios.
AB  - The lecithin/sphingomyelin (L/S) ratio after cold acetone precipitation is widely
      used to predict fetal lung maturity. The separation of saturated lecithin, the
      main component of surfactant, is the basis for using the precipitation procedure
      but there is still a controversy as to whether cold acetone precipitable lecithin
      can be equated with saturated lecithin. Following up a previous paper in which
      the effect of cold acetone precipitation on phospholipids of amniotic fluid was
      studied, the present work reports that non-precipitated L/S and
      phosphatidylglycerol/sphingomyelin (PG/S) ratios correlate well with the
      precipitated L/S ratio (r = 0.93, r = 0.84, n = 92). The predictive value of both
      non-precipitated L/S and PG/S ratios has been studied when a "positive" result
      predicts a precipitated L/S ratio > or = 2.0, and proposes a L/S ratio > or = 4.7
      and a PG/S ratio > or = 0.8 to predict fetal lung maturity, when cold acetone
      precipitation step is omitted.

PMID- 7569273
TI  - [Can we modify the pathogenesis of coronary disease? Introduction].
AB  - Recently the European Societies of Cardiology Atherosclerosis and Hypertension
      have published a document of Recommendations on the Prevention of Coronary
      Disease in Clinical Practice. The information given in the document has proven
      that a reduction in cholesterol reduces the risk of the onset of new coronary as
      well as cardiovascular mortality. It has been accepted that such reduction can
      induce the regression of the atheroma plaque, and the slowing of its progression.
      In Spain cardiovascular mortality has progressively decreased since 1975. This is
      true for the coronary caused mortality and the secondary to a cerebrovascular
      disease, the latter being that where the greatest change has been noticed, as
      well as in women. Probably, this trend may be explained by a better control on
      hypertension, as well as by a more adequate hospital net. Spain has one of the
      lowest rates of mortality due to coronary disease among the industrialized
      countries. Nevertheless, the cardiovascular mortality is still the first cause of
      death in Spain. Spanish cardiologist are convinced that the relationship between
      the levels of cholesterol and coronary risk happened in Spain, in quantitative
      terms, differently than in Central Europe and the USA. They consider that the
      "Mediterranean diet" is the protective factor.

PMID- 7569274
TI  - Effects of magnesium, sodium, calcium or potassium intakes on magnesium content
      in rat skeletal muscle.
AB  - Magnesium skeletal (myocardium and gastrocnemius) content has been studied in
      rats supplemented with 30 mM dissolutions of Mg2+, Na+, Ca2+ and K+ in drinking
      water, for 7 or 30 days. In both muscles, the ingestion of Mg2+ for 30 days
      increased Mg2+ content, while Ca2+ and K+ supplementation caused a significant
      drop. The increase in Na+ ingestion reduced Mg2+ content in gastrocnemius. There
      were no significant differences between control and animals supplemented for 7
      days. These results suggest that, in the case of supplementation situations, the
      control mechanisms of the Mg2+ tissular content have a lower gain than those of
      Na+ and K+ of one order of magnitude.

PMID- 7569278
TI  - Age-related increased 14C-arachidonic acid uptake by platelets in normal
      subjects.
AB  - Arachidonic acid uptake activity (pmol/10(8) platelets min) measured in platelets
      obtained from normal subjects was significantly higher in over-forty year old
      (3.53 +/- 0.38) than in under-forty year old subjects (2.33 +/- 0.12). No
      significant correlations were found between the arachidonic acid uptake activity
      and fasting plasma glucose, total cholesterol, HDL-cholesterol or triglyceride
      levels. The arachidonic acid uptake activity was significantly reduced by the
      presence of indomethacin in platelets obtained from both under and over-forty
      year old subjects, and by the presence of nordihydroguaiaretic acid in platelets
      obtained from over-forty year old subjects. In conclusion, these data show that
      arachidonate uptake activity by platelets increased with age. This increase was
      abolished when platelets were incubated in the presence of inhibitors of the
      arachidonic acid metabolism.

PMID- 7569276
TI  - Effect of domoic acid on brain amino acid levels.
AB  - The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes
      in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala,
      GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala,
      striatum, cortex and midbrain). The most affected amino acid is the GABA, the
      main inhibitory amino acid neurotransmitter, whereas glutamate, the main
      excitatory amino acid, is not affected. The rat brain regions that seem to be the
      main target of the Dom action belong to the limbic system (hippocampus,
      amygdala). The possible implication of the amino acids in the actions of Dom is
      also discussed.

PMID- 7569279
TI  - He-Ne laser has no effect on cell cycle phases of human colon adenocarcinoma
      cells.
AB  - The aim of this study is to investigate the effect of He-Ne continuous laser
      (12.6 mW, 632.8 nm), at low energy densities, on cell cycle synchronization of
      monolayer growing human colon adenocarcinoma cell line. The doubling time of cell
      culture was used as optimum time to verify laser effect. The monolayer cultures
      were exposed to single doses of different energy densities (0.042 J cm-2 to 1.68
      J cm-2). The nuclear DNA content has been studied by flow cytometry to obtain the
      cell percentage in each cell cycle phase. Results show no effect of He-Ne laser
      irradiation on cell cycle short time synchronization under the previously
      mentioned conditions and cell type. Higher energy densities and multiple
      irradiations should be investigated.

PMID- 7569277
TI  - Dose-response effects of VIP on the rabbit exocrine pancreatic secretion.
      Comparison with PACAP-27 actions.
AB  - A dose-response study of the effects of vasoactive intestinal peptide (VIP) on
      the exocrine pancreatic secretion of the rabbit has been made. Furthermore, the
      actions of VIP and pituitary adenylate cyclase activating peptide (PACAP) on the
      exocrine pancreatic secretion were compared at a similar molar dose. After the
      infusion of VIP a linear dose-response relationship for pancreatic flow rate and
      bicarbonate output, up to the dose of 4 micrograms/kg, was observed. VIP acts as
      a partial agonist of secretin, the rabbit pancreas being less sensitive to VIP
      compared with other mammals. Moreover, VIP did not significantly stimulate the
      pancreatic protein output. PACAP stimulated the hydroelectrolyte fraction of the
      exocrine pancreatic secretion in a similar manner to that of VIP. Unlike what was
      observed with VIP, PACAP, on the same molar basis, significantly stimulated the
      protein and amylase outputs. Furthermore, PACAP releases VIP, so that the action
      of PACAP on the hydroelectrolyte fraction may be partially mediated by VIP; on
      the other hand, VIP is not involved in the effect of PACAP on the pancreatic
      enzyme secretion of this species.

PMID- 7569280
TI  - Increase in cardiac output and PEEP as mechanism of pulmonary optimization.
AB  - The influence of cardiac output (CO) and PEEP on pulmonary shunt (Qs/Qt) has been
      the subjects of considerable investigation but findings are controversial. The
      role of CO and PEEP on 19 isolated rabbit lung preparations perfused with hypoxic
      mixture (6% CO2, 10% O2, and 84% N2), which resulted in a constant oxygen venous
      pressure (64 +/- 5.6 mmHg) has been studied. The first group of 11 preparations
      were used to study the influence of CO modifications with room air ventilation on
      the Qs/Qt when the CO rises in 48%; in the second group simultaneous
      modifications in CO and PEEP (0.5 and 10 cm H2O) were performed. A positive
      correlation (p < 0.01) in Qs/Qt (0.048 +/- 0.04 to 0.12933 +/- 0.09) was found
      when the CO increased in the first experimental group, the fluid filtration rate
      (FFR) also increased and the pulmonary vascular resistance (PVR) remained stable.
      In the second group an increase of 5 and 10 cm H2O of PEEP at constant CO reduced
      the Qs/Qt (0.0361 +/- 0.02 to 0.0184 +/- 0.006) while it increased the arterio
      venous oxygen difference, PVR and FFR. During high CO conditions increase of 5
      and 10 cm H2O of PEEP reduced the Qs/Qt (0.099 +/- 0.03 to 0.027 +/- 0.02) and
      FFR. These data suggest that when the Qs/Qt is increased, the use of PEEP can
      compensate the ventilation/perfusion alterations and restore pulmonary gas
      exchange.

PMID- 7569282
TI  - [The Campodimele study: 24-hour blood pressure in rural life style subjects].
AB  - The present paper is aimed at investigating the daily blood pressure in subjects
      with a rural style of life with the purpose of detecting whether or not the blood
      pressure regimen is influenced as expected because of the stress less prominent
      in the non-urban areas. Control data were obtained by the study of age- and sex
      matching subjects with a metropolitan style of life. The results indicate the
      blood pressure has a lower daily level in rural subjects as compared to urban
      subjects. The daily baric impact is also lower, suggesting that the blood
      pressure regimen is really less pronounced in those who live according to a rural
      style of life. Such a lower magnitude allows us to experimentally suggest that
      the rural life is concrete in protecting the hemodynamic system from the higher
      level of blood pressure which are observable in subjects who live according to a
      metropolitan style of life. Interestingly, the expected phase anticipation in
      blood pressure circadian rhythm of rural subjects was not detected, as the wake
      up time was not so anticipated to act as a synchronizer.

PMID- 7569281
TI  - [Dynamics of psychoactive substance dependence].

PMID- 7569284
TI  - [Effects on the coagulation-fibrinolysis system of a single oral dose of
      mesoglycan at the beginning and at the end of a prolonged treatment in man].
AB  - We evaluated the mesoglycan effects on the coagulative-fibrinolytic system in 10
      patients with euglobulin lysis time (ELT) over 180 minutes. A mathematical model
      was used to analyze such phenomena. 100 mg of mesoglycan was administered to 10
      patients for 14 days. The following parameters were evaluated: tissue plasminogen
      activator (t-PA), plasminogen activator inhibitor (PAI-1), euglobulin lysis time
      (ELT), plasminogen, alpha 2 antiplasmin, prothrombin time (PT), activated partial
      thromboplastin time (aPTT), thrombin clotting time (TCT), and fibrinogen. Those
      parameters were evaluated on the first and on the last day of the mesoglycan
      treatment at the following times: 0 (basal), 2, 4, 6, 8, 10 and 12 hours. Our
      results suggest that the mesoglycan is able to reduce a profibrinolytic activity
      without any influence on the coagulative-fibrinolytic system, at the baseline
      conditions and after chronic administration. The pharmacodynamic study and the
      statistical analysis using our mathematic model resulted to be statistically
      significant.

PMID- 7569283
TI  - [Effects of 2 single oral doses of mesoglycan on the coagulation-fibrinolysis
      system in man. A pharmacodynamic study].
AB  - In this study the profibrinolytic activity of two single oral doses of mesoglycan
      was evaluated. Furthermore, a mathematical model describing the patterns of the
      resulting phenomena was applied. Ten patients with impaired fibrinolytic system
      (euglobulin lysis time > 180 min) were enrolled in the study. In the morning
      following a 24 hour fast period, the patients were given orally a single dose
      (100 and 50 mg) of mesoglycan and placebo, with an interval of 48 hours between
      each treatment. The following parameters were evaluated at the time 0 and after
      2, 4, 6, 8, 10 and 12 hours from each administration: tissue plasminogen
      activator (t-PA) and its inhibitor PAI-1, euglobulin lysis time, plasminogen and
      alfa-2-antiplasmin as indexes of the fibrinolytic system; aPTT, TT, fibrinogen as
      indexes of the hemostatic-coagulative system. Mesoglycan showed a dose-dependent
      profibrinolytic activity, that was also present after placebo but in a less
      entity. The mathematical study confirms the experimental observations and thus
      may allow to describe, with a high degree of approximation, the in vivo
      pharmacology of mesoglycan through the use of the mathematical function.

PMID- 7569285
TI  - [Glutathione in the treatment of chronic fatty liver diseases].
AB  - In chronic steatosic liver disease, alcohol or non-alcohol related or HBV, HCV,
      HDV associated, a reduction in hepatic glutathione and, consequently, in the
      detoxifying effects of hepatocytes is observed. Intravenous administration of
      high dose glutathione in patients with chronic steatosic liver disease has shown
      that glutathione significantly improves the rate of some hepatic tests
      (bilirubin, GOT, GPT, GT) even several months after treatment interruption.
      Further confirmation of the efficacy of GSH treatment is provided by the
      reduction of malondialdehyde, a marker of hepatic cell damage. The optimal
      results obtained in patients receiving 1800 mg/die/i.v. advocate the use of this
      high dosage.

PMID- 7569288
TI  - [Preliminary findings on clinical and immunological effects of subcutaneously
      administered interleukin-2 + alpha-interferon combination in the treatment of
      advanced renal carcinoma].

PMID- 7569290
TI  - [Idiopathic myelofibrosis. Main pathogenetic, prognostic and therapeutic
      aspects].
AB  - Primary myelofibrosis is a complex disorder characterized by bone marrow fibrosis
      with no apparent cause. It is known in literature under a wide number of terms,
      reflecting the variety of clinical features and the different pathogenetic
      hypotheses. In most cases it is plain that marrow fibrosis is secondary to a
      clonal myeloproliferative disorder and, in particular, to the presence of
      abnormal megakaryocytes secreting (MKDGF/PDGF); but probably some other growth
      factors synthesized by megakaryocytes and contained in platelet alpha-granules
      are involved. The molecular event that determines the advantage of the clonal
      growth is, at present, unknown, and the pathogenetic importance of some
      chromosome anomalies is still under discussion. Over the last years, besides
      megakaryocyte dysplasia, several fibrogenetic mechanisms such as a bone marrow
      immune damage have been taken into consideration. Studies on prognostic factors
      regarding the main clinical, hematological and histological parameters have given
      conflicting results, because of low incidence of the disease, different criteria
      used for the diagnosis, and different terms of the clinic presentation of the
      pathology. Although a great deal of progress has been made in terms of
      pathogenetic mechanisms, a lot of questions must be still definitively settled,
      further in depth studies still have to go into many matters.

PMID- 7569289
TI  - [What is the real prevalence of hypertension in obesity?].
AB  - Many confounding variables (age, sex, race, income level) may contribute to an
      incorrect estimate of the prevalence of hypertension in the obese population.
      Furthermore, as far as methodology is concerned, both casual morning BP
      measurement and, the use, in the obese patient, of inappropriate cuffs both also
      contribute significantly to the overestimation with the inclusion of false
      positives even in relevant percentages. Different types of obesity (android or
      gynoid; visceral or subcutaneous) should be considered when enrolling obese
      patients in prevalence studies being android or visceral obesity at a higher
      hypertensive risk. At last and overall, universally recognized cutoff-points for
      obesity and hypertension should always be used when studying prevalence of
      hypertension among general population and/or among obese patients. When such
      conditions are not taken into account, inaccurate and misleading conclusions on
      the real prevalence of hypertension in obesity may result.

PMID- 7569291
TI  - [Communication with the patient: a duty useful to physicians, a benefit to
      patients].

PMID- 7569287
TI  - Effects of lactitol [correction of lactilol] on hepatic encephalopathy and plasma
      amino-acid imbalance.
AB  - Hepatic encephalopathy in liver cirrhosis is due to several factors, including
      amino acid imbalance and hyperammonemia. Lactitol [correction of lactilol], a non
      adsorbable disaccharide, improves hepatic encephalopathy increasing bowel
      movements, modifying colonic bacteria and pH, and reducing blood ammonium. Ten
      patients with liver cirrhosis and longstanding stable hepatic encephalopathy were
      treated, after a period of drugs wash-out, with lactitol. A significant
      improvement of hepatic encephalopathy was observed, with a significant decrease
      of blood ammonium, related with the increase of stool frequency/day. Atrial
      natriuretic peptide decreased as well. Moreover, an increase of the ratio of
      plasma aliphatic amino acids (valine, leucine and isoleucine)/aromatic amino acid
      (tyrosine and phenylalanine) was observed. Lactitol is an effective drug in the
      treatment of chronic hepatic encephalopathy; its mechanism of action involves not
      only a decrease of blood ammonium but also modifications of the degree of plasma
      amino acid imbalance, and fluid and circulatory adjustments.

PMID- 7569286
TI  - [Primary non-Hodgkin's lymphoma of the bone. Description of 2 cases].
AB  - Primary bone non Hodgkin's lymphomas (PBL) are approximately 5% of extranodal
      lymphomas and 5% of all primary bone tumors. A standard treatment has not been
      codified yet. The most received only radiotherapy but recently it was introduced
      combined modality treatment with radiotherapy plus chemotherapy or chemotherapy
      alone. The authors describe two cases of high grade PBL that received combined
      treatment with chemotherapy (VACOP-B regimen and monochemotherapy with
      mitoxantrone respectively) and radiotherapy. The patients achieved complete
      remission and up to day are alive and disease free at 33 and 15 months from the
      diagnosis respectively.

PMID- 7569293
TI  - [Course of peripheral arterial diseases].
AB  - During January and November 1983 we examined 230 patients by means of doppler
      evaluation for suspect of peripheral arterial disease. We identified 105 subjects
      with peripheral arterial disease. During September and November 1993 we tried to
      convoke again all 230 subjects. Altogether we followed 215 subjects (95 with
      peripheral arterial disease and 120 without). Sixty-three patients died and we
      analysed the cause of death. Forty-seven out of 95 patients (49.5%) with
      peripheral arterial disease died and only 16 out of 120 subjects (13.3%) without
      peripheral arterial disease. Twenty-five out of 47 deaths (53.2%) happened among
      the patients with peripheral arterial disease. Age, severity of peripheral
      arterial disease (measured by ankle-arm pressure ratio) and the presence of a
      carotid bruit were associated with death. The natural history of peripheral
      arterial disease has been characterized by a worsening of the intermittent
      claudication in 52.1% of patients but only 18.6% presented a progression toward a
      superior class of the Fontaine classification. In conclusion, the peripheral
      arterial disease, despite his apparently benign course, represents a clinical
      event that must not be overlooked, because the risk of cardiovascular mortality
      is high. The measurement of ankle-arm pressure ratio allows a good definition of
      the severity of peripheral arterial disease and therefore represents a valid
      prognostic criterion.

PMID- 7569295
TI  - [A case of resistant sideropenic anemia. Adult celiac disease].
AB  - We report a case of a woman affected by sideropenic anaemia (SA) for about thirty
      years and never restored with a therapy with iron per os. At the age of 60 years
      a malabsorption syndrome appears and an adult celiac disease was diagnosed (ACD).
      The SA was therefore and since the beginning the only symptom of the
      malabsorption. When SA is resistant to the iron per os therapy, we always should
      suspect a malabsorption due to CD often olygosymptomatic in the adult patient. We
      would now recommend, in presence of resistant SA, the weight of jejunum biopsy,
      as well as his excessive importance, when it shows an apparently not specific
      finding of mucosa atrophia with chronic phlogosis.

PMID- 7569292
TI  - [Epidemiology of hepatitis C virus infection in hemodialysis. A study of the
      Gargano area].
AB  - In order to evaluate epidemiological features of hepatitis C virus infection in
      patients with chronic renal failure, we enrolled 80 haemodialyzed subjects in
      four centers of Gargano area (Southern Italy). In a 28 months follow-up we
      checked antiHCV antibodies by EIA II and viraemia by polymerase chain reaction.
      Seroprevalence of HCV infection was 35%, while incidence was 2.4%/year; viraemia
      was detected in 62.5% of antiHCV+ and in only one of antiHCV-. In our opinion
      there is a definitive need of special precautions (or isolation of antiHCV+) in
      haemodialysis units to avoid community-acquired HCV infection.

PMID- 7569294
TI  - Cholinergic modulation of growth hormone, prolactin and thyroid stimulating
      hormone responses to thyrotropin-releasing hormone in normal aging.
AB  - Endocrine changes occur during the normal aging process. These include
      alterations in GH, TSH and, to a lesser extent, PRL secretion. Pyrodistigmine
      (PD) increases basal GH secretion in a widely variable manner and partially
      reverses the blunted GH response to GHRH found in elderly subjects. The aims of
      this study were to verify the finding of a paradoxical GH response to TRH (200
      micrograms iv) and to evaluate the effect of priming with PD (120 mg orally) on
      basal and TRH-stimulated GH, TSH and PRL secretion in 7 euthyroid subjects (aged
      75-96 years). Hormonal responses after control saline and PD were also evaluated.
      PD did not modify TSH or PRL responses to TRH. A slight increase in GH secretion
      was observed after PD. A clear-cut increase in GH levels after TRH was found in 4
      out of 7 subjects. TRH-induced GH secretion was significantly increased by
      pretreatment with PD. Functional abnormalities in the neuroendocrine control of
      GH secretion in aging could explain, at least in part, the appearance of GH
      release after TRH. Cholinergic neurotransmission, which is thought to be
      stimulated by PD administration, seems to be involved in the non-specific GH
      release after TRH administration in elderly subjects.

PMID- 7569296
TI  - [Pheochromocytoma-gastric leiomyoblastoma association. A possible expression of
      Carney's triad. A case report].
AB  - The case of a 28 yrs old female patient affected by pheochromocytoma and gastric
      leiomyoblastoma was described. The simultaneous presence of these neoplasms in a
      young woman supported the diagnosis of the clinical syndrome known as "Carney's
      triad".

PMID- 7569297
TI  - Churg-Strauss syndrome with peripheral polyneuropathy refractory to steroideal
      and immunosuppressive therapy successfully treated with plasma exchange.

PMID- 7569298
TI  - Influence of electromagnetism on genomic and associated structures.

PMID- 7569299
TI  - [Communication of bad facts. To inform or not to inform the patient: a choice
      between 2 alternatives?].
AB  - In the last thirty years physicians changed their attitudes regarding the
      communication of the diagnosis to their patients. The prevailing tendency in the
      past to protect patients against emotional distress thought to be caused by the
      breaking of bad news has been replaced by the acknowledgment of the patient's
      right to be informed about their condition. This acknowledgement has not been
      accompanied by a different cognitive approach to patients: the decision to inform
      or not inform the patient about his/her diagnosis still depends more on doctor
      than on patient characteristics. It has been demonstrated that patients are
      usually not well informed and known less about their illness than doctors suppose
      they do. Technical jargon and unclear communication contribute to the patients'
      difficulty in understanding correctly the information provided by their doctors.
      If patients perceive genuine interest and feel supported by their doctors, only
      very few prefer not "to know". To be informed about the illness does not seem to
      be associated with increased emotional distress on the long term but, on the
      contrary, facilitates patients' adjustment to illness.

PMID- 7569301
TI  - The effectiveness of skin care protocols for pressure ulcers.
AB  - Pressure ulcers (PU) remain a serious healthcare problem in the United States.
      This study investigated the effectiveness of a prevention and early intervention
      program in reducing the prevalence of pressure ulcers (i.e., the number or the
      percentage of persons with pressure ulcers at a given time) in a rehabilitation
      hospital. The Braden Scale for Predicting Pressure Sore Risk was used to assess
      subjects' PU risk. Protocols were established for PU stages consistent with the
      National Pressure Ulcer Advisory Panel consensus statement on pressure ulcers.
      Staff were educated about PUs and the specific protocols for prevention and
      treatment. Concurrent quarterly prevalence audits on a total of 116 patients were
      conducted for 1 year. An audit also was done 16 months after protocols had been
      established. There was a 60% decrease in pressure ulcer prevalence from the 25%
      baseline to the 10% found at the audit following implementation of the protocols.

PMID- 7569300
TI  - Is the nursing profession a toxic work environment?

PMID- 7569302
TI  - What are the educational needs of prospective family caregivers of newly disabled
      adults?
AB  - What are the needs of family caregivers of newly disabled adults? Research to
      date has focused on the needs of family members of patients in critical care
      units and of family members who have been in the caregiver role at home for some
      time. No studies could be found on the perceptions of individuals facing the
      decision to assume the family caregiver role for a newly disabled adult
      anticipating discharge from a physical rehabilitation or medical-surgical nursing
      unit. Watson's philosophy of science and caring provided the theoretical basis
      for this study. The Elaine Matthis Educational Wants of Family Caregivers of
      Disabled Adults Questionnaire was used to assess the perceptions of prospective
      family caregivers visiting newly disabled adults in an urban medical center. The
      results of this research are offered to help nurses understand the feelings of
      uncertainty about the new and unexpected role that family caregivers face and to
      help nurses meet the needs of families preparing to take disabled adult relatives
      home.

PMID- 7569303
TI  - The rehabilitation nurse in the home care setting: treating chronic wounds as a
      disability.
AB  - Rehabilitation nurses have moved into the home care setting; along with other
      home care nurses, they treat clients with chronic wounds. A rehabilitation nurse,
      however, views the homebound client needing wound care as having a disability
      that requires lifestyle modification. Rehabilitation nurses also treat clients
      with other disabilities who are at risk for developing wounds, so they are in an
      ideal position to instruct clients in wound prevention. Rehabilitation nurses in
      home care have the skills and expertise to assess clients needing wound care for
      deficits that might otherwise be overlooked.

PMID- 7569306
TI  - Maintaining skin integrity: setting the standard in a rehabilitation facility.
AB  - Impaired skin integrity and a high risk for developing it are two of the more
      common nursing diagnoses made in the rehabilitation setting. Pressure sores and
      their consequences are directly related to increased length of stay for patients
      and can create higher costs for the institution. Most of the sequelae of pressure
      sores can be avoided, as the identification, prevention, and treatment of
      pressure sores have become more standardized. The rehabilitation facility
      discussed in this article developed a standard of care for the maintenance of
      skin integrity, a pressure sore protocol, and nursing care plans to provide a
      standardized format for nursing care. The standard was designed to ensure
      consistency among the nursing staff when they assess, plan, evaluate, and
      document care of patients who have pressure sores or are at risk of developing
      them. The standard also created a mechanism for evaluating the knowledge and
      skill of the nursing staff in preventing and treating pressure sores. This
      article describes the components of the standard of care and its supporting
      policies as well as its implementation and use.

PMID- 7569304
TI  - Using a wheelchair activity as a learning experience for student nurses.
AB  - An experiential activity was conducted as part of a nursing course at a
      university in the Midwest to determine whether simulating a physical disability
      by using a wheelchair could be a valuable educational strategy. The goal was to
      increase nursing students' awareness of disability, sensitivity to people with
      disabilities, and understanding of the importance of self-efficacy, as well as to
      enhance their learning about the research process, which was one of the course
      objectives. While the results of this activity were not statistically
      significant, the content analysis of the qualitative data showed an effect on the
      experimental group. This analysis suggested that the enactment was a beneficial
      learning experience that increased nursing students' depth of understanding about
      what life is like for a disabled person in a wheelchair.

PMID- 7569305
TI  - Group learning for adults with disabilities or chronic disease.
AB  - In some facilities, group learning has been used to teach adults who have various
      disabilities or chronic diseases (e.g., diabetes, cardiac problems, cancer,
      Parkinson's disease, spinal cord injury). The following literature review
      discusses the advantages of group learning, which include peer support,
      individuals' learning and gaining motivation from each other, reduced feelings of
      isolation, and opportunities to share problems and goals. It appears likely that
      greater use of group learning could enhance rehabilitation efforts for adults.

PMID- 7569307
TI  - A credentialing program for nursing staff caring for pediatric patients with an
      ilizarov apparatus.
AB  - The purpose of this article is to provide an overview of an educational program
      that was implemented at a postacute pediatric rehabilitation facility to prepare
      the nursing staff to provide quality care for patients undergoing limb
      lengthening. Patients undergoing limb lengthening and limb reconstruction by the
      Ilizarov orthopedic method wear a highly complex external fixation device that
      has numerous variations. As such, it is a type of apparatus that pediatric
      rehabilitation nurses are unaccustomed to dealing with in the clinical arena. The
      nursing department at the facility described in this article undertook an
      intensive educational and credentialing program to ensure staff competency,
      parent satisfaction, and quality patient care for cases involving limb
      lengthening and reconstruction.

PMID- 7569308
TI  - When a serious illness hits home.

PMID- 7569309
TI  - Apoptosis parallels lymphopoiesis in bone marrow transplantation and HIV disease.
AB  - Apoptosis has been implicated in a variety of physiological processes ranging
      from tissue modeling to deletion of autoreactive T lymphocytes during thymic
      development. The recent finding that a large proportion of peripheral T cells
      from HIV-infected subjects (corrected from subjects) apoptose in culture raises
      an important issue: does this represent a pathologic mechanism by which the virus
      disrupts the immune system, or a normal physiologic response to virus-mediated T
      cell loss? To study the potential relationship between apoptosis and
      lymphopoiesis, we compared apoptosis rates in unstimulated lymphocyte cultures
      from healthy subjects, HIV+ gay men, and bone marrow transplant (BMT) recipients
      undergoing immune reconstruction. BMT recipients were chosen because they undergo
      massive regeneration of lymphocytes following marrow ablation and graft infusion.
      The data obtained in BMT recipients suggests that elevated apoptosis accompanies,
      and is the consequence of, elevated lymphopoiesis. We also found a strong inverse
      relationship between in vitro T-cell apoptosis rates and peripheral T-cell
      counts. These results provide new interpretation for elevated apoptosis observed
      in HIV-infected individuals--that it reflects increased T-cell turnover
      consequent to virus-mediated destruction of CD4+ T-cells.

PMID- 7569310
TI  - Quantitative and qualitative changes in CD44 and MEL-14 expression by T cells in
      C57BL/6 mice during aging.
AB  - Aging is associated with a decrease in the functional activity of T cells. We
      have explored age-related alterations in CD44 and MEL-14 expression by spleen
      cells bearing the Thy1.2, CD4 or CD8 antigens in C57BL/6 mice at 2, 8, 15 and 23
      months of age. The membrane expression of CD44 and MEL-14 molecules can be used
      to distinguish naive (CD44low, MEL-14high) from preactivated/memory (CD44high,
      MEL-14low) T cells. Our results show that the proportion of CD4+ splenic cells
      begins to decrease at an intermediate age (8-month-old mice), whereas the
      proportion of CD8+ cells remains unaltered. The proportion of CD4+ and CD8+
      splenic cells with the CD44high memory phenotype was increased at an early stage
      of aging (in 8-month-old mice) without a concomitant change in MEL-14 expression.
      In older mice, MEL-14 expression decreased on CD4+ but not on CD8+ subsets.
      Recent studies have reported that following activation, the expression of CD44
      molecules containing additional, so-called variable exons can be detected. By
      PCR, we observed an increase in CD44 transcripts containing the v6 or v7 variable
      exons in murine lymph nodes at the age of 15 months. Our results suggest that v6-
      or v7-containing variants of CD44 may be involved in the development of memory
      cells. Taken together, these results suggest that the trafficking of memory T
      cells in aging may be altered by quantitative and/or qualitative differences in
      the expression of molecules involved in lymphocyte recirculation.

PMID- 7569311
TI  - In vivo cytotoxic T-lymphocyte induction may take place via CD8 T helper
      lymphocytes.
AB  - Immunization of mice with peptide constructs, consisting of a determinant
      recognized by T cytotoxic cells colinearly linked to a determinant recognized by
      T helper cells (TDc-TDh) was able to induce cytotoxic T lymphocytes in vivo.
      Interestingly, this induction could be achieved in the absence of adjuvant in non
      depleted as well as in CD4(+)-cell-depleted BALB/c mice. In the latter case,
      induction took place simultaneously with the activation of CD8+ T helper cells
      specific for a TDh contained within the sequence of the TDc RIQRGPGRAFVTIGK from
      the immunodominant V3 loop of HIV1 gp120. The possible implications of these
      findings in HIV infection and AIDS disease are discussed.

PMID- 7569312
TI  - The costimulatory and differentiating activity of soluble class I MHC antigens
      for an autologous thymocyte population.
AB  - Combined cultivation of macrophages with syngeneic thymocytes resulted in
      accumulation of soluble H-2Kk antigens in culture medium. Incubation of intact
      autologous thymocytes with these soluble class I MHC molecules was shown to
      induce functional maturation of thymocytes assayed in local graft-vs-host
      reaction. Similar thymocyte costimulating activity was detected for the papain
      solubilized purified H-2Kk antigens. Soluble class I antigens were shown to
      costimulate IL2 production by thymocytes in response to submitogenic doses of
      exogenous IL2 and to increase PHA-induced thymocyte proliferation. Soluble class
      I molecules were shown to increase the level of expression of function-associated
      membrane antigens, H-2Kk, CD8 and CD4, and to trigger thymocyte differentiation.
      The expression of I-Ak antigens remained invariable. It was also shown that
      soluble autologous class I molecules may function as direct amplifiers of
      thymocyte proliferation in autologous, but not allogeneic, mixed leukocyte
      reactions. It is concluded that soluble MHC class I molecules are capable of
      triggering functional and phenotype differentiation of syngeneic thymocytes and
      acting as restricted coaccessory molecules when thymocyte activation is induced
      by a submitogenic dose of different stimuli.

PMID- 7569313
TI  - . . . and such are little lymphocytes made of.

PMID- 7569317
TI  - Growth phase-dependent variations in the outer membrane protein profile of
      Brucella melitensis.
AB  - Changes in Brucella cell envelope protein profiles were investigated with batch
      cultures of B. melitensis strain 16M in a 2-litre fermenter. Analysis of
      expression of outer membrane proteins (OMP) (apparent molecular masses of 10,
      16.5, 19, 25-27, 31-34, 36-38 and 89 kDa) and heat-shock protein DnaK (73 kDa)
      was performed with monoclonal antibodies (mAb) and immunoblotting techniques.
      Synthesis of the 89-kDa OMP and the heat-shock protein DnaK was invariant during
      B. melitensis growth. Expression of the 10-, 19- and 36-38-kDa minor OMPs was
      never detected. Variations in profiles of some OMPs, i.e. 25-27-kDa and 31-34-kDa
      major proteins and 16.5-kDa minor protein, occurred during growth stages,
      principally at the end of the exponential growth phase. These variations
      consisted of shifts in apparent molecular masses for the 25-27-kDa and 31-34-kDa
      OMPs and of peptidoglycan association for the 16.5-kDa OMP. Therefore, whereas
      the strong association of major OMPs with peptidoglycan was confirmed, results
      suggested that the 16.5-kDa minor OMP is also a peptidoglycan-associated protein.

PMID- 7569316
TI  - Electrophoretic mobility of external invertase from free and gel-immobilized
      yeast cells.
AB  - Electrophoretic mobility of secreted invertase (E.C. 3.2.1.26) from gelatin
      immobilized yeast cells was analysed and compared with that of secreted invertase
      from freely suspended batch-grown cells. Invertase from immobilized cells showed
      a lower mobility after 24 h of incubation, in medium containing either glucose or
      raffinose as carbon source. Changes in invertase mobility were also followed in a
      time course both for immobilized and for freely suspended batch-grown cells.
      Mobility of invertase from free cells increased after approximately 15 h of
      incubation, independently of the carbon source, whilst that of invertase from
      immobilized cells remained constant. The differences observed were attributed to
      a different level of glycosylation of the protein moiety in free and immobilized
      cells. The amount of mannoproteins in the cell walls of immobilized cells was
      also investigated by ConA-ferritin labelling and quantification of ferritin
      particle density in ultrathin sections; the results of this experiment showed a
      higher content of mannoproteins in the walls of immobilized cells when compared
      with free cells. As a whole, these results are indicative of physiological
      changes that can be ascribed to the peculiar microenvironment of gel-immobilized
      cells.

PMID- 7569319
TI  - Introduction of Pseudomonas aeruginosa mutator phage D3112 into Alcaligenes
      eutrophus strain CH34.
AB  - We have investigated the possibility of growing mutator phages from Pseudomonas
      aeruginosa on various isolates of Alcaligenes eutrophus. Although none out of 10
      A. eutrophus strains were susceptible to infection with any of the phages tested,
      phage D3112 could be readily transferred in our model strain CH34 by means of an
      RP4::D3112 plasmid. CH34/RP4::D3112 lysogens were stable and produced phages.
      However, neither mitomycin C nor UV treatment increased the phage yield.

PMID- 7569315
TI  - Expression and immunogenicity of an 18-residue epitope of HIV1 gp41 inserted in
      the flagellar protein of a Salmonella live vaccine.
AB  - A synthetic oligonucleotide specifying residues 735-752 of the product of the env
      gene of HIV1 IIIB was inserted by blunt-end ligation at restriction sites in the
      hypervariable, antigenically determinant region IV of two flagellin genes. Its
      integration, in frame and correct orientation, into gene fliC(d) in plasmid
      pLS408 allowed production of functional flagella when the plasmid was placed in a
      flagellin-negative aroA live-vaccine Salmonella dublin strain, SL5928. Bacteria
      thus made motile were immobilized and agglutinated by anti-(735-752 peptide)
      serum; expression was also shown by immunoelectron-microscopy and by Western blot
      of whole-cell lysates. Enzyme immunoassay (EIA) of sera of mice given three doses
      by intraperitoneal injection of the live-vaccine strain producing chimeric
      flagellin, or of concentrated flagella from it, showed production of antibody
      with affinity for the peptide, and in some sera, also for r-gp160. Pooled serum
      from mice given five i.p. doses of the live vaccine strain expressing the gp41
      epitope at the surface of its flagellar filaments had higher titres of anti
      peptide and anti-r-gp160 antibody and weak neutralizing activity on the IIIB
      isolate (90% neutralization at 1/100). The sera of nine mice given two doses of
      the live vaccine by the oral route had either no or only very low titres of
      antibody to flagellar antigen d; they were therefore not tested for anti-peptide
      activity.

PMID- 7569318
TI  - Development of a species-specific probe for Mycobacterium xenopi.
AB  - In Europe, Mycobacterium xenopi is a frequently isolated species among
      opportunist mycobacteria, and represents one of the main agents of pulmonary
      infection due to non-tuberculous mycobacteria. Conventional identification of
      mycobacteria is a time-consuming and laborious process. In this study, we propose
      a rapid and simple method for the identification of M. xenopi using polymerase
      chain reaction. The amplified product consists of a specific probe, present in
      all 38 M. xenopi strains tested, which could not be amplified and did not present
      cross-hybridization with a set of 110 strains belonging to 23 other mycobacterial
      species. The probe was cloned and sequenced. Comparison with data bases revealed
      no significant homologies with previously described sequences.

PMID- 7569320
TI  - The effects of tunicamycin on secretion, adhesion and activities of the cellulase
      complex of Clostridium cellulolyticum, ATCC 35319.
AB  - The effects of tunicamycin, an inhibitor of N-asparagine-linked glycosylation, on
      the secretion, adhesion and activities of the cellulase complex produced by
      Clostridium cellulolyticum have been studied. Tunicamycin at 0.1 micrograms/ml
      slightly inhibited growth on cellobiose. Endoglucanase, p
      nitrophenylcellobiosidase and avicelase activities of the "Avicel"-adsorbed
      fraction from a culture grown with this drug were decreased 4.4-, 1.4- and 12.2
      fold, respectively. During growth on cellulose, tunicamycin considerably
      inhibited growth and adhesion of cells on their substrate (only 28% of the cells
      were bound to cellulose). SDS-PAGE mobilities of some proteins excreted during
      growth with the drug were different from those of proteins from control cultures;
      the native Avicel-adsorbed fraction (PH2O) consisted of three major components of
      molecular weights about 135, 90 and 68 kDa, whereas in the presence of
      tunicamycin (0.1 micrograms/ml), the Avicel-adsorbed fraction (PH2OT) contained
      only a major band of 105 kDa, and the proteins of 135 and 68 kDa appeared weakly.
      By using the "Dig Glycan Detection" kit, some proteins appeared to be
      glycosylated, such as the 135-, 95-, 47- and 40-kDa proteins. Moreover, the
      affinity for Avicel and the avicelase activity decreased dramatically for the
      Avicel-adsorbed fraction from a culture grown with the drug. The remaining
      avicelase activity of the PH2O fraction in the presence of specific P135
      antiserum was 50% of the initial activity, whereas CMCase and pNPCbase were not
      affected. The glycosylated protein of 135 kDa played a prominent role in the
      adhesion and avicelase activity of C. cellulolyticum. Moreover, the endoglucanase
      activity in a culture broth from tunicamycin-grown cells was more thermolabile
      and protease-sensitive than that from control cultures.

PMID- 7569322
TI  - Taxonomic diversity of anaerobic glycerol dissimilation in the
      Enterobacteriaceae.
AB  - A total of 1,123 strains representing 128 taxa in the Enterobacteriaceae (named
      species or subspecies and genomic species) were screened for the presence of
      glycerol dehydrogenases and 1,3-propanediol dehydrogenase. Only eight taxa,
      Citrobacter freundii sensu stricto, C. youngae, C. braakii, C. werkmanii,
      Citrobacter genomospecies 10 and 11, Enterobacter gergoviae and Klebsiella
      pneumoniae subsp. pneumoniae could grow fermentatively on glycerol and possessed
      both glycerol dehydrogenase type I (induced by glycerol and dihydroxyacetone) and
      1,3-propanediol dehydrogenase which are typical enzymes of the anaerobic glycerol
      dissimilation pathway. Six other species, C. koseri, E. aerogenes, E.
      intermedium, K. oxytoca, K. planticola and K. terrigena could not grow
      fermentatively on glycerol and possessed a glycerol dehydrogenase type I but no
      1,3-propanediol dehydrogenase. Other glycerol dehydrogenases types were found:
      type II (induced by glycerol and hydroxyacetone), type III (induced by glycerol
      only) and type IV (induced by hydroxyacetone only). They were widely distributed
      among the Enterobacteriaceae. Classification and identification may take
      advantage of tests exploring the dissimilation of glycerol.

PMID- 7569321
TI  - Phylogenetic analyses of the ATP-binding constituents of bacterial
      extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases.
AB  - Thirty-eight ATP-binding cassette (ABC) protein constituents of bacterial
      extracytoplasmic receptor-dependent nutrient uptake systems, including one
      homologous chloroplast protein were analysed for sequence conservation and
      phylogenetic relatedness. The proteins were generally found to cluster in
      accordance with the clustering patterns previously observed for the
      extracytoplasmic receptors and the transmembrane channel-forming constituents of
      these permeases. The results suggest that these transport systems evolved from a
      single primordial system with minimal shuffling of the three dissimilar protein
      constituents of the systems.

PMID- 7569314
TI  - Studies of the anaerobically induced promoter pnirB and the improved expression
      of bacterial antigens.
AB  - The promoter of the Escherichia coli gene nirB is induced by both the presence of
      nitrite in the environment and by low oxygen tensions. It has been used to direct
      the high-level expression of heterologous proteins by E. coli strains in
      fermentors, and attenuated Salmonella strains expressing foreign proteins under
      nirB promoter (pnir) control have efficiently induced an immune response against
      these proteins. The genes encoding two different E. coli envelope proteins, the
      outer membrane protein LamB and the periplasmic protein MalE, were placed under
      pnir control on pBR322 derivatives, and both proteins were expressed at high
      levels during anaerobic growth. Our results showed that the expression level of
      MalE was influenced by the distance between the pnir promoter and the Shine
      Dalgarno sequence: the highest levels were obtained by the longest constructs
      made; pnir directed a 4-fold increase in the level of MalE expression relative to
      the level reached by the previously described ptac-MalE expression vector. The
      best pnir construct produced 25 mg of MalE protein per 5 x 10(11) bacteria, which
      represents over 20% of total cell protein. Overexpression of MalE was well
      tolerated by E. coli, even under strict anaerobic conditions; for LamB, optimal
      induction was achieved under partial anaerobiosis. A MalE-HIV1 hybrid protein (33
      residues from the V3 loop of HIV1 gp160 inserted into site 133 of MalE) was also
      overexpressed at a similar yield under pnir control, without apparent degradation
      of the hybrid protein. Moreover, when expressed in attenuated aroA S. typhimurium
      strain SL3261, the plasmids carrying malE and malE-HIV genes were stable in vitro
      and in vivo.

PMID- 7569323
TI  - Purification, properties and DNA sequence of the D-lactate dehydrogenase from
      Leuconostoc mesenteroides subsp. cremoris.
AB  - The complete sequence of the D-lactate dehydrogenase (D-ldh) gene from
      Leuconostoc mesenteroides subsp. cremoris, cloned in Escherichia coli, were
      determined. The deduced amino acid sequence showed homologies with all members of
      the D-specific-2-hydroxyacid dehydrogenase family. Furthermore, the essential
      residues detected so far as being involved in catalysis were also conserved.
      Purification of the enzyme revealed physico-chemical properties corresponding to
      those predicted from the sequence. The active enzyme was a dimer of 40-kDa
      subunits. The Km values for pyruvate, lactate, NADH and NAD were 0.3, 19, 0.03
      and 0.16 mM, indicating that the enzyme reduced pyruvate in vivo. Besides the D
      LDH activity, L. mesenteroides subsp. cremoris also displayed HicDH enzymatic
      activity, catalysing the reduction of pyruvate analogs. The purified D-LDH
      displayed low HicDH-type activity; therefore, differences in specificity profiles
      between the crude extract and the purified enzyme suggested the occurrence of a
      specific HicDH.

PMID- 7569324
TI  - The sulphydryl-activated cytolysin and a sphingomyelinase C are the major
      membrane-damaging factors involved in cooperative (CAMP-like) haemolysis of
      Listeria spp.
AB  - The negative mutant approach was used in this study to identify listerial
      cytolytic factors involved in cooperative haemolysis (CAMP-like phenomenon) with
      Staphylococcus aureus and Rhodococcus equi. A Listeria monocytogenes non
      haemolytic mutant specifically impaired in listeriolysin O (LLO) production gave
      no CAMP reaction with S. aureus, and was virtually CAMP-negative with R. equi,
      indicating that the listerial sulphydryl-activated toxin played a major role in
      cooperative haemolysis. This was confirmed by direct evidence using purified LLO
      and alveolysin (from Bacillus alvei) in diffusion CAMP assays. To our knowledge,
      this is the first evidence of involvement of a sulphydryl-activated toxin in
      cooperative lytic processes. Phosphatidylcholine- and phosphatidylinositol
      specific phospholipases C from L. monocytogenes did not seem to significantly
      contribute to cooperative haemolysis, as the corresponding mutants displayed wild
      type CAMP reactions. In contrast, the sphingomyelinase C from Listeria iva-novii
      was the cytolytic factor responsible for the characteristic shovel-shaped CAMP
      reaction shown by this listerial species with R. equi. Possible mechanisms of
      lytic cooperation are discussed.

PMID- 7569325
TI  - DNA:DNA hybridization and chemotaxonomic studies of Thermus scotoductus.
AB  - The species Thermus scotoductus was recently described as containing several non
      pigmented isolates from Selfoss, Iceland, and the X-1 strain from the USA
      (Kristjansson et al., 1994). In this study, we performed DNA:DNA hybridizations
      and chemotaxonomic studies on several non-pigmented Thermus isolates from other
      geographical areas to assess their relationship to the strains originally
      assigned to this species. The results of DNA:DNA hybridizations showed that
      strains NH and Dl from London and strains Vl-7a and Vl-13 from Vizela, Portugal,
      belonged to T. scotoductus. T. scotoductus X-1 (ATCC 27978) was composed of two
      stable colony types, one of which had a major glycolipid different from the one
      present in the other colony type and from all other Thermus strains examined as
      well. The fatty acid composition of the isolates from Selfoss and London were
      practically identical. However, the fatty acid composition of strain X-1, the
      individual colony types of this strain and the Vizela strains were different from
      the Selfoss-London isolates and from each other. Another non-pigmented strain,
      designated SPS-11, belonged to a different DNA homology group.

PMID- 7569327
TI  - Association between different clinical manifestations of Lyme disease and
      different species of Borrelia burgdorferi sensu lato.
AB  - Borrelia burgdorferi sensu lato, the aetiological agent of Lyme disease, has been
      subdivided into three species: B. burgdorferi sensu stricto, B. garinii and B.
      afzelii. We and other authors have hypothesized an association between the three
      species of B. burgdorferi sensu lato and some of the different clinical
      manifestations of Lyme disease. In order to demonstrate this hypothesis, we
      analysed twenty-nine isolates cultured from patients with different symptoms. The
      method used was multilocus enzyme electrophoresis: twelve genetic loci were
      characterized on the basis of the electrophoretic mobility of their products, and
      twenty-eight distinctive allele profiles (electrophoretic types) were
      distinguished, among which mean genetic diversity per locus was 0.649. Cluster
      analysis of a matrix of genetic distances between paired electrophoretic types
      revealed three primary divisions separated at genetic distances greater than 0.7
      and corresponding to the three species of B. burgdorferi sensu lato. Ten strains
      obtained from skin of patients with erythema chronicum migrans (the primary stage
      of the disease) were assigned to the three different species. All the six strains
      isolated from patients with acrodermatitis chronica atrophicans were of the
      species B. afzelii, which was not found to be associated with another chronic
      manifestation of Lyme disease. Arthritis was caused prevalently by B. burgdorferi
      sensu stricto, and neuroborreliosis by B. burgdorferi sensu stricto and B.
      garinii. In conclusion, our results confirm the association between some of the
      different chronic manifestations of the disease and the species of B. burgdorferi
      sensu lato.

PMID- 7569326
TI  - Mycobacterium tuberculosis strains unidentified using the IS6110 probe can be
      detected by oligonucleotides derived from the Mt308 sequence.

PMID- 7569328
TI  - Cloning of a novel polymorphic GC-rich repetitive DNA from Mycobacterium bovis.
AB  - A repetitive DNA from a wild-type Mycobacterium bovis isolate was cloned and
      characterized. The repeated segment was present in M. bovis and M. tuberculosis
      but was absent from the six other mycobacteria tested. Sequence analysis
      demonstrated that this repetitive element belonged to the polymorphic GC-rich
      repeat sequence type, a family of interspersed repeated DNA. This fragment, when
      used as a probe in restriction fragment length polymorphism analyses, was able to
      detect polymorphism in M. bovis genotypes that went undetected when the
      established IS6110 was used as a probe. This repetitive element should be useful
      in epidemiological studies of bovine tuberculosis.

PMID- 7569329
TI  - Rapid identification of Mycobacterium xenopi from bacterial colonies or "Bactec"
      culture by the polymerase chain reaction and a luminescent sandwich hybridization
      assay.
AB  - Oligonucleotide primers were used in the polymerase chain reaction (PCR) to
      amplify a specific 584-bp DNA fragment, located in the 16S RNA gene of
      Mycobacterium xenopi. This set of primers, X222 and X224, was able to
      discriminate between the pathogen and other mycobacterial species as well as non
      mycobacterial strains; it detected down to 3 fg of M. xenopi DNA, i.e. about one
      genome equivalent. These oligonucleotide primers proved suitable for the routine
      identification of M. xenopi cultures, starting from one single colony on solid
      medium or from a liquid culture in Middelbrook 12B "Bactec" medium. In addition,
      a luminescent hybridization assay was designed for use on PCR-amplified DNA. This
      system, which, for capture, relied on a matrix-bound oligonucleotide (M30)
      specific for the genus Mycobacterium and, for detection, on a biotinylated xenopi
      specific X221 probe, proved fully specific, highly sensitive and rapid for the
      evaluation of M. xenopi Bactec cultures at low growth index.

PMID- 7569330
TI  - Alpha 1-proteinase inhibitor abrogates proteolytic and secretagogue activity of
      cystic fibrosis sputum.
AB  - Airway disease in cystic fibrosis (CF) is characterized by neutrophil-dominated
      chronic inflammation with an excess of uninhibited neutrophil elastase (NE),
      which is regarded as an important factor in progressive lung destruction.
      Therefore, inhalation of alpha 1-proteinase inhibitor (alpha 1-PI) seems to be a
      reasonable therapeutic approach. To estimate its therapeutic potential, we
      quantitatively investigated the in vitro interactions of exogenous alpha 1-PI
      with CF sputum samples (n = 28). High NE and alpha 1-PI concentrations were
      detected in CF sputum (6.03 +/- 0.78 and 2.56 +/- 0.16 mumol/l, respectively).
      There was significant NE activity (2.6 +/- 0.4 U/l) due to both the surplus of NE
      and proteolytic degradation of alpha 1-PI. Addition of exogenous alpha 1-PI
      resulted in a dose-dependent inhibition of NE activity in CF sputum; > 90%
      inhibition was achieved at 10 micrograms/ml alpha 1-PI. Purified NE as well as CF
      sputum potently induced secretion from porcine tracheal glands. Corresponding to
      inhibition of NE activity, CF sputum-induced secretion was also inhibited by
      exogenous alpha 1-PI; > 90% inhibition was also achieved at 10 micrograms/ml
      alpha 1-PI. Incubation of exogenous alpha 1-PI with CF sputum for 24 h did not
      reduce the inhibitory effects. From our in vitro results we conclude that
      inhalation of alpha 1-PI might effectively inhibit both NE activity and airway
      gland hypersecretion in CF airways.

PMID- 7569331
TI  - Fibronectin and hyaluronan in bronchoalveolar lavage fluid from young patients
      with chronic obstructive pulmonary diseases.
AB  - Fibronectin (FN) and hyaluronan (HA) in bronchoalveolar lavage fluid (BALF) and
      FN released by alveolar macrophages (AM) were examined in 7 nonsmoking healthy
      control subjects, and 20 smoking patients with chronic obstructive pulmonary
      diseases (COPD). All patients and subjects were no more than 40 years old.
      According to the 95% confidence limits of HA and FN in BALF from nonsmoking
      healthy control subjects, the smoking patients were divided into two groups,
      those who had HA and FN levels within the limits for nonsmoking controls were
      classified as the first group (group 1) and those with levels above the control
      limits were classified as the second group (group 2). Our data showed that the
      concentrations of HA and FN in BALF and FN released by AM were significantly
      higher in group 2 than in group 1 patients. There were also significant
      differences between the two groups in pulmonary function measurements (DLco,
      FEV1, and FEV1/FVC) which were lower in group 2. HA levels in group 2 patients
      correlated directly with counts of inflammatory cells in BALF (BALF cells/ml, and
      numbers/ml of total cells, macrophages, neutrophils and lymphocytes), and the
      concentration of FN released by AM, and showed an inverse correlation with
      pulmonary function (DLco and FEV1/FVC). Our results suggest that the inflammatory
      repair response and fibrosis may play a role in the development of emphysema in
      young patients with COPD.

PMID- 7569332
TI  - Mechanisms of 3-carene-induced bronchoconstriction in the isolated guinea pig
      lung.
AB  - Inhaled 3-carene at a concentration of 5,000 mg/m3 caused bronchoconstriction in
      isolated, ventilated and perfused guinea pig lungs. This effect was inhibited by
      the cyclooxygenase inhibitor diclofenac (100 microM) and the
      thromboxane/prostaglandin endoperoxide-receptor antagonist L-670,596 (1 microM).
      3-Carene exposure also increased the amount of thromboxane in the perfusate from
      the lungs. In cultured calf pulmonary arterial endothelial cells 3-carene caused
      a dose-related release of arachidonic acid. Thus, the results obtained in this
      experimental model may have implications in the understanding of the
      pathophysiology of 3-carene-induced obstructive pulmonary disease in humans.

PMID- 7569333
TI  - Sarcoidosis patients have bronchial hyperreactivity and signs of mast cell
      activation in their bronchoalveolar lavage.
AB  - An increased (p < 0.001) frequency of bronchial hyperreactivity (BHR) was found
      in sarcoidosis patients as compared with healthy volunteers. The patients had
      more mast cells (p < 0.001) and tryptase (p < 0.001) in their bronchoalveolar
      lavage fluid, but there were no differences between BHR-positive and BHR-negative
      patients. Furthermore, the bronchoalveolar lavage fluid concentrations of
      macrophages, lymphocytes, and of the soluble components albumin, fibronectin, and
      vitronectin were also elevated in the sarcoidosis patients, indicating an ongoing
      inflammation in the airways and/or in the interstitium. We observed no
      significant differences in the parameters when the sarcoidosis patients were
      subdivided into BHR, clinical activity, or chest X-ray stages. Our findings may
      indicate a multifactorial background to the hyperreactivity.

PMID- 7569335
TI  - Stent placement is justifiable in end-stage patients with malignant airway
      tumours.
AB  - Extraluminal tumour compression can be treated with the use of stenting. In 8
      patients with end-stage malignant tumours of the tracheobronchial tree, tumor
      compression of the major airways became apparent after Nd-YAG laser debulking.
      Dumon-type stents (Endoxane), were inserted under general anaesthesia. There were
      no complications during and after stent insertion. All stents were well
      tolerated, with significant symptomatic relief in all patients. This symptomatic
      relief was considered worthwhile, despite the limited duration of palliation and
      the pre-terminal stage of the patients. Tumour progression after stent insertion
      was usually beyond any treatment possibility, except additional laser
      coagulation. The median survival was 2 months and the longest palliation was 11
      months.

PMID- 7569334
TI  - Intravenous injection of acetaldehyde but not ethanol induces histamine-mediated
      bronchoconstriction in guinea pigs.
AB  - Recently ethanol-induced bronchoconstriction associated with elevated serum
      levels of acetaldehyde and histamine was reported in Japanese asthmatic patients,
      but there is no investigation of the airway response to intravenous injection of
      acetaldehyde. We therefore performed a study in guinea pigs to test the
      hypothesis that intravenous injection of acetaldehyde has bronchospastic action
      via histamine release. At first, we investigated the airway response to
      increasing doses (8.0, 26.4, and 80 mg/ml) of injected ethanol or acetaldehyde in
      guinea pigs. Secondarily, increasing doses of acetaldehyde were injected in
      guinea pigs pretreated with an intraperitoneal injection of 20 mg/kg
      diphenhydramine or saline (control). Finally, injection of acetaldehyde was
      performed after intraperitoneal injection of 0.5 mg/kg atropine sulfate or saline
      (control). Injected acetaldehyde caused bronchoconstriction in a dose-dependent
      manner, but ethanol did not. The bronchoconstriction induced by injected
      acetaldehyde was completely prevented by pretreatment with diphenhydramine.
      Atropine had no preventing effect against the acetaldehyde-induced
      bronchoconstriction. In conclusion, intravenous injection of acetaldehyde causes
      bronchoconstriction via histamine release in guinea pigs.

PMID- 7569336
TI  - Tracheobronchopathia osteochondroplastica. Report of a young man with severe
      disease and retrospective review of 18 cases.
AB  - Tracheobronchopathia osteochondroplastica (TPO) is a rare condition of unclear
      cause. Sporadic cases have been published from all over the world, but some
      geographical differences in the occurrence may exist. The condition is
      characterized by cartilaginous or bony outgrowths into the lumen of the
      tracheobronchial tree. Clinicians should include this disease in the list of
      differential diagnoses when confronted with symptoms like persistent and often
      productive cough, haemoptysis, dyspnoea and wheeze. If the condition is
      extensive, there may occur unexpected and acute clinical problems. We describe
      the case of a young man in whom we diagnosed a severe form of TPO while examining
      him for asthma. This patient suffered also from ozaena and the combination of
      these two conditions is rather common. We also retrospectively reviewed our
      material of 18 cases with this condition.

PMID- 7569337
TI  - Cerebral infarction due to a spontaneous tumor embolus from lung cancer.
AB  - A cerebral infarction of the left occipital lobe developed in a 65-year-old man
      with squamous cell carcinoma of the right lung. Neurological examinations and
      brain CT showed findings typical of ordinary infarction. Postmortem examination
      revealed a tumor embolus within the posterior cerebral artery. Such spontaneous
      tumor emboli large enough to obstruct a larger-sized artery are rare.

PMID- 7569338
TI  - Exogenous surfactant application in respiratory failure due to chronic
      obstructive pulmonary disease.
AB  - Recent results of basic research on regulation of surfactant secretion and
      surfactant physiology not only in the alveolus but also in peripheral small
      airways allow the conclusion that disorders in surfactant homeostasis may
      contribute to the pathophysiology of airway obstruction and hyperinflation. We
      therefore hypothesized that patients with respiratory failure due to obstructive
      lung disease may benefit from exogenous surfactant. Here we report a case that
      indicates the clinical situation to be considered for treatment with exogenous
      surfactant. The benefit for the patient was successful weaning from the
      ventilator. Improvements in effective compliance, resistance and blood gas
      parameters were observed following surfactant application.

PMID- 7569339
TI  - Tracheal glomus tumour.
AB  - A glomus tumour situated at the posterior wall of the trachea in a 65-year-old
      man presenting with dyspnoea and haemoptysis is described. The tumour was excised
      with an Nd-YAG laser, with no visible recurrence a year later. This is the fifth
      reported case of tracheal glomus tumour.

PMID- 7569340
TI  - Combined amyloidosis of the upper and lower respiratory tract.
AB  - Pulmonary and laryngeal manifestations of localized and organ-limited amyloidosis
      are sometimes seen, although pulmonary and laryngeotracheal amyloidosis are not
      always associated. Diagnosis can only be established histologically by the
      characteristic green birefringence in polarized light after Congo red staining
      and by immunohistochemical techniques. We describe the case of a 77-year-old
      woman who presented with hoarseness and an unproductive cough due to extensive
      amyloid deposits in both the upper and lower respiratory tract,
      immunohistochemically proven as the A lambda-type.

PMID- 7569342
TI  - Cat-scratch disease associated with pleural effusions and encephalopathy in a
      child.
AB  - Cat-scratch disease has been associated with a variety of systemic
      manifestations. We present a case of cat-scratch disease associated with
      bilateral pleural effusions and encephalopathy in a child. The particular
      combination of findings reported here may be more ubiquitous than formerly
      suspected and widen the clinical description of this condition.

PMID- 7569341
TI  - Sideroelastosis pulmonum: cause or consequence of the pulmonary veno-occlusive
      disease?
AB  - In a 66-year-old patient morphologic features of a pulmonary veno-occlusive
      disease were found. Besides, a striking foreign body giant cell reaction with
      phagocytosis of altered elastic tissue in totally or partially occluded venous
      blood vessels resembled the so-called pulmonary sideroelastosis, an entity
      originally described by Ceelen. In this case report, a possible pathogenetic
      relation between sideroelastosis pulmonum and pulmonary veno-occlusive disease is
      discussed.

PMID- 7569343
TI  - Orthopnea due to an aneurysm of the thoracic aorta.
AB  - Aneurysms of the thoracoic aorta may on rare occasions lead to shortness of
      breath by external compression of the tracheobronchial tree. We report the case
      of a patient who presented with orthopnea due to extensive compression of the
      trachea and the major airways by a large aneurysm of the ascending aorta.

PMID- 7569344
TI  - Reticular pseudodrusen. A risk factor in age-related maculopathy.
AB  - BACKGROUND: Reticular pseudodrusen refer to a yellow interlacing network 125
      microns to 250 microns wide appearing first in the superior outer macula and then
      extending circumferentially and beyond. Unlike true drusen, they do not fluoresce
      on fluorescein or indocyanine green angiography, and are best seen in red-free
      light or with the He-Ne laser of the scanning laser ophthalmoscope. METHODS: One
      hundred patients have been seen in our retinal practice with this clinical
      feature in the past 3 years. RESULTS: All had some manifestation of age-related
      maculopathy (ARM), and 66% had or subsequently developed subretinal new vessels
      in one or both eyes. The appearance is attributed to changes in the choroid.
      CONCLUSIONS: Reticular pseudodrusen are an easily recognizable clinical sign, and
      may be an important risk factor for choroidal neovascularization in ARM.

PMID- 7569346
TI  - Surgery for subfoveal membranes in myopia, angioid streaks, and other disorders.
AB  - OBJECTIVE: A retrospective analysis of patients who underwent surgical removal of
      subfoveal neovascular membranes caused by factors other than age-related macular
      degeneration (AMD) and presumed ocular histoplasmosis syndrome (POHS) was
      performed. METHODS: 17 eyes (16 patients) were identified in which subfoveal
      neovascularization was caused by myopic degeneration (5 eyes), angioid streaks (5
      eyes of 4 patients), idiopathic neovascularization (4 eyes), punctate inner
      choroidopathy (1 eye), multifocal choroiditis (1 eye), or candida chorioretinitis
      (1 eye). RESULTS: Visual acuity remained stable after surgery in 10 of 17 eyes
      (59%), improved by 2 or more Snellen lines in 6 eyes (35%) and decreased in 1 eye
      (6%). Preoperative visual acuity was 20/80 or better in only 1 of 17 eyes (6%),
      but 5 of 17 eyes (29%) achieved postoperative visual acuity of 20/80 or better.
      Intraoperative and postoperative complications included peripheral retinal tears
      (1 eye), peripheral rhegmatogenous retinal detachment (1 eye), and mild cataract
      formation (1 eye). Subretinal neovascularization recurred after surgical removal
      in 4 eyes, 2 of which underwent repeat surgery. CONCLUSION: Visual acuity
      remained stable or improved in 94% of eyes after surgical removal of subfoveal
      neovascularization, but postoperative visual acuity better than 20/80 was
      achieved in a minority of eyes.

PMID- 7569345
TI  - Vitrectomy for vitreomacular traction syndrome with macular detachment.
AB  - PURPOSE: To describe the clinical characteristics of the vitreomacular traction
      syndrome with macular detachment and to report our surgical experience with this
      condition. METHODS: A retrospective chart and photographic review was performed
      on nine patients (nine eyes) who had a symptomatic decrease in visual acuity from
      a macular traction retinal detachment caused by vitreomacular traction syndrome.
      Vitrectomy was performed in each eye to reattach the retina. RESULTS:
      Intraoperative observation confirmed partial posterior vitreous separation with
      adherence of the posterior hyaloid to the detached retina and separation of the
      posterior hyaloid from the attached retina. After surgery the macula was
      reattached in seven eyes (78%). Visual acuity was improved in four eyes, stable
      in four eyes, and worse in one eye. CONCLUSION: Macular detachment may occur
      secondary to vitreomacular traction syndrome. Although the retina may be
      reattached surgically in these cases, visual improvement may be limited by
      chronic detachment, premacular fibrosis, cystoid macular edema, or macular
      schisis.

PMID- 7569347
TI  - Corticosteroid-sparing strategies in the treatment of retinal vasculitis in
      systemic lupus erythematosus.
AB  - BACKGROUND: Systemic corticosteroids have been traditionally used in the therapy
      of retinal vasculitis in patients with systemic lupus erythematosus. The high
      morbidity associated with long-term corticosteroid therapy has prompted the use
      of corticosteroid-sparing strategies with cytotoxic agents. METHODS: This
      retrospective study summarizes the authors' experience of the last 10 years
      including 9 systemic lupus erythematosus patients with retinal vasculitis who
      required treatment for longer than 6 months. RESULTS: Seven of these patients
      were treated with cytotoxic agents. Average follow-up was 39 months. Inflammation
      was controlled clinically and angiographically in all patients using the
      following therapeutic regimens: systemic corticosteroids and hydroxychloroquine
      (n = 1 patient); systemic corticosteroids and cytotoxic chemotherapy (n = 6);
      cytotoxic chemotherapy and hydroxychloroquine (n = 1); and hydroxychloroquine
      alone (n = 1). Visual acuity was preserved (> 20/30) or improved in all patients.
      All patients retained excellent control of their systemic disease during their
      follow-up. Side effects of cytotoxic drugs requiring discontinuation of all
      chemotherapy were not encountered in this group; Imuran therapy did result in
      substantial adverse effects necessitating its replacement with other drugs.
      CONCLUSION: These results suggest a valuable role for corticosteroid-sparing
      drugs in the therapy of retinal vasculitis associated with systemic lupus
      erythematosus.

PMID- 7569348
TI  - Endogenous endophthalmitis simulating retinoblastoma. The 1993 David and Mary
      Seslen Endowment Lecture.
AB  - BACKGROUND: Among conditions that can simulate retinoblastoma, endogenous
      endophthalmitis is quite rare. METHODS: Case records of six children with unusual
      forms of endogenous endophthalmitis, all of whom were referred to the authors
      because retinoblastoma was a strong diagnostic consideration, were reviewed. The
      clinical features that may help differentiate atypical endophthalmitis from
      retinoblastoma were investigated. RESULTS: The final diagnosis in these cases
      included idiopathic subretinal abscess, streptococcal endophthalmitis, idiopathic
      retinovitreal abscess, cytomegalovirus endophthalmitis, Candida endophthalmitis,
      and meningococcal endophthalmitis. All of the affected children presented
      primarily with ocular findings without serious systemic infection. Although these
      conditions closely simulated retinoblastoma, they were more likely to have signs
      of concurrent or prior inflammation. CONCLUSION: Differentiation between
      infectious conditions and retinoblastoma can sometimes be difficult, but clues as
      to the diagnosis can be obtained from careful clinical examination.

PMID- 7569349
TI  - Phakic retinal detachments in the elderly.
AB  - PURPOSE: To discover if clinical nontraumatic phakic retinal detachments in the
      elderly possess characteristics that distinguish them from similar cases in
      younger persons. METHODS: A retrospective study of 100 consecutive cases in
      patients aged 70 years and older was performed. Recorded data included patient
      age and sex, type and location of retinal break, extent of detachment, and
      associated vitreoretinal pathology. RESULTS: Approximately 90% of retinal breaks
      were horseshoe tears, and the majority were located in the superior temporal
      quadrant. Horseshoe tears confined to the posterior margin of the vitreous base
      were responsible for retinal detachments in 30% of cases, and an additional 36%
      of breaks were located anterior to the equator. CONCLUSION: The incidence of this
      type of anterior break is higher than that previously described for phakic
      retinal detachments, although previous studies have not discussed break types as
      a function of old age. Anterior horseshoe tears, which cause many phakic retinal
      detachments in the elderly, may not be caused by acute posterior vitreous
      detachment, but rather to persistent chronic traction on the vitreous base after
      posterior vitreous detachment.

PMID- 7569350
TI  - Laser indirect ophthalmoscope photocoagulation and scleral depression for
      rhegmatogenous retinal detachment.
AB  - BACKGROUND: Transconjunctival cryotherapy or laser photocoagulation with
      simultaneous Eisner funnel scleral depression has been used to treat selected
      cases of rhegmatogenous retinal detachment. There are no studies to date
      reporting the use of the laser indirect ophthalmoscope coupled with scleral
      depression for treating retinal detachment. METHODS: 16 consecutive patients (18
      retinal detachments in 17 eyes) were enrolled in a prospective, uncontrolled
      clinical trial using the laser indirect ophthalmoscope with scleral depression as
      the sole treatment for retinal detachment. The region immediately surrounding the
      break where subretinal fluid was present was directly treated rather than
      demarcated. All patients were treated with local anesthesia in an outpatient
      setting. RESULTS: Complete retinal reattachment was initially achieved in 14
      (78%) of 18 eyes after scleral depression and laser alone. Significant
      postoperative complications of scleral depression with laser indirect
      ophthalmoscope photocoagulation included macular pucker (2 eyes), late recurrent
      rhegmatogenous retinal detachment without proliferative vitreoretinopathy (1
      eye), and late recurrent rhegmatogenous retinal detachment with proliferative
      vitreoretinopathy (2 eyes). Failure of initial treatment to flatten the retina,
      late recurrent retinal detachment, macular pucker, or proliferative
      vitreoretinopathy led to scleral buckling and/or vitrectomy in 6 (86%) of the 7
      eyes with clinical detachment and 3 (30%) of the 10 eyes with localized
      detachment. Final retinal reattachment at the last follow-up examination was
      achieved in all 17 eyes with subsequent surgical procedures. CONCLUSION: Although
      scleral depression with laser indirect ophthalmoscope photocoagulation is a
      noninvasive outpatient surgical procedure that is capable of flattening selected
      retinal detachments, its use cannot be recommended because of the relatively high
      rate of postoperative complications requiring further surgical procedures.

PMID- 7569352
TI  - Expression of glial fibrillary acidic protein in the rat retina after exposure to
      psychostimulants.
AB  - PURPOSE: Neonatal exposure to psychostimulants is known to produce morphologic
      alterations in the developing visual system of rats. This study was designed to
      evaluate the extent of retinal astrocytic response by using the astrocyte
      localized protein, glial fibrillary acidic protein, after neonatal exposure to
      cocaine and amphetamine. METHODS: Male Wistar rats were given 15 mg/kg body
      weight/day of cocaine hydrochloride, subcutaneously, from postnatal days 0 to 6,
      13, and 29 and were killed at postnatal days 7, 14, and 30; other rats received
      10 mg/kg body weight/day of d-amphetamine sulfate following the same protocols.
      Control rats were given saline or were not manipulated. After transcardiac
      perfusion with 4% paraformaldehyde whole mounts of flat retinas were processed
      for glial fibrillary acidic protein immunohistochemistry. Retinas displaying
      lesions from the amphetamine groups were processed for electron microscopy;
      vertical semithin and ultrathin sections were observed. RESULTS: In cocaine
      treated rats extensive sheets of proliferating astrocytes presenting a
      preferential peripheral localization could be identified. In the amphetamine
      exposed rats an enhanced expression of glial fibrillary acidic protein was
      detected in widespread "loci" of astrocytes observed throughout the whole retinal
      surface; at postnatal day 30 sheets of proliferating astrocytes could also be
      identified. CONCLUSION: Exposure to psychostimulants during active development
      induced different types of astrocytic responses in the retina, which, as an end
      result, can lead to functional changes due to the disruption of the retina
      structural organization.

PMID- 7569353
TI  - Choroidal blastomycosis. A report of two cases.
AB  - PURPOSE: To review the presentation and course of choroidal blastomycosis, a rare
      chorioretinal mycotic infection, which results from disseminated blastomycosis.
      METHODS: Two cases of disseminated blastomycosis with ocular infection limited to
      the choroid are presented. Each patient was diagnosed through biopsy of skin
      lesions demonstrating the characteristic histologic features and the budding
      yeast. RESULTS: Systemic evaluation revealed extensive disseminated disease with
      involvement of the eye, lung, skin, bone and joint, central nervous system, and
      genitourinary system. Both patients were successfully treated with intravenous
      amphotericin B with elimination of ocular and systemic disease. CONCLUSION:
      Although rare, blastomycosis can result in choroidal mycotic infection in immune
      competent individuals. Tissue biopsy to confirm the diagnosis and extensive
      systemic evaluation are required.

PMID- 7569351
TI  - Interpretation of intraocular and serum antibody levels in necrotizing retinitis.
AB  - BACKGROUND: Intraocular antibodies have been measured as a diagnostic aid in
      necrotizing retinitis but interpretation of results may be difficult. METHODS:
      Vitreous or aqueous and serum immunoglobulin G antibodies to toxoplasmosis,
      cytomegalovirus, herpes simplex virus I and II, and varicella zoster virus were
      subjected to enzyme-linked immunosorbent assay in 27 patients with necrotizing
      retinitis and 15 control patients. A quotient was derived quantitating the amount
      of excess antibody in the eye compared to serum. Different interpretative rules
      were analyzed to determine which yielded the highest sensitivity and specificity.
      RESULTS: The highest intraocular antibody relative to serum among the 4
      antibodies correctly predicted the final clinical diagnosis in 21 of 27 patients,
      for a sensitivity of 78% and a specificity of 90%. Interpretive rules that relied
      on a high numeric value of the antibody quotient or did not consider the relative
      ranking of the four antibody quotients were less sensitive and specific because
      multiple antibodies were detected in most eyes. The technique was safe and rapid.
      CONCLUSION: Interpretation of antibody titers in intraocular fluids is
      facilitated by testing several relevant antibodies and comparing the results. The
      technique may be helpful to diagnose necrotizing retinitis and to ascertain viral
      cause in acute retinal necrosis.

PMID- 7569354
TI  - Comparison of techniques for transscleral diode photocoagulation in the rabbit.
AB  - PURPOSE: To assess the optimum probe design and treatment parameters for
      transscleral diode laser retinopexy. METHODS: Transscleral diode photocoagulation
      was performed on the eyes of Dutch-belted rabbits using three different
      transscleral probes: a straight, 400-microns diameter probe; a prism-tipped 400
      microns diameter probe; and a prism-tipped 900-microns diameter probe. RESULTS:
      Transscleral diode photocoagulation with all three probe types was an effective
      method of ablating the retina and creating chorioretinal adhesions. Both the burn
      diameter and the mean radiant output energy requirement increased as the burn
      duration and probe aperture diameter was increased. Explosive retinal holes were
      encountered in 12% of the burns created with the straight probe. The use of the
      prism-tipped probes significantly reduced the incidence of retinal holes to < 4%
      (P < 0.005). Histopathologically, all burns were grade III in intensity with
      severe choroidal injury. In many of the burns, there was histopathologic evidence
      of thermal injury to the inner sclera. The frequency of these inner scleral
      changes was reduced with a long burn duration (5 seconds). CONCLUSION: This study
      confirms that diode transscleral photocoagulation is a feasible method of thermal
      retinopexy. The use of the prism-tipped probes and long duration burns resulted
      in the fewest adverse reactions.

PMID- 7569355
TI  - Juvenile coats disease associated with epiretinal membrane formation.

PMID- 7569356
TI  - A simple and inexpensive system for the removal of silicone oil through a 20
      gauge opening.

PMID- 7569359
TI  - [1st Congress of the Croatian Rheumatology Association. Opatija, 1994.
      Abstracts].

PMID- 7569357
TI  - The skewer technique for removal of the dislocated lens.

PMID- 7569358
TI  - High dose intravitreal ganciclovir.

PMID- 7569363
TI  - Type of statistical techniques in rheumatology and internal medicine journals.
AB  - A comparison of the prevalence and type of statistical analysis used in internal
      medicine and rheumatology journals was done. Four representative journals of each
      specialty were selected and twelve original articles were randomly obtained from
      each journal. The papers were reviewed twice within a three month interval by the
      same evaluator following published definitions for classification. The
      rheumatology journals tended to use fewer (80 versus 115) and simpler statistical
      techniques (X3 = 4.28, DF = 1, p = 0.03; OR, 95% CI = 3.21, 1.05-10.85). There
      was a statistical difference in the utilization of statistical procedures among
      journals in the four categories evaluated. Seven statistical techniques were
      required to have access to 86% of statistical tests used in rheumatology journals
      (t-tests, contingency tables, descriptive statistics, non-parametric comparisons,
      anova, multiple regression, and Pearson's correlation). The internal medicine
      journals required six statistical procedures to have access to 85% of the tests
      (contingency tables, survival analysis, epidemiologic statistics, t-tests, non
      parametric statistics, and anova). Our results could be useful to plan medical
      education in biostatistics emphasizing the statistical techniques most commonly
      used in these areas.

PMID- 7569362
TI  - [Hepatitis C virus infection and membranoproliferative glomerulonephritis].
AB  - BACKGROUND AND METHODS: A possible association between hepatitis C virus
      infection (HCV) and membranoproliferative glomerulonephritis (MPGN) or membranous
      glomerulonephritis has recently been reported. The pathogenesis of this entity
      appears to be immunologically mediated. The purpose of this report is to describe
      the clinical, laboratory, and histopathological features of three patients with
      chronic HCV infection, without hepatitis B virus disease or autoimmune diseases,
      but with glomerular disease. RESULTS: All three patients had chronic hepatopathy
      stigmata, ascitis, peripheral edema, and normal blood pressure values. Laboratory
      results showed mild liver function abnormalities and normal levels of blood
      nitrogenous waste products. Microscopic hematuria, hypoalbuminemia, and variable
      proteinuria without hypercholesterolemia were found in all cases. All three had
      positive rheumatoid factor. Only one patient had positive antinuclear antibodies
      and antimitochondrial antibodies at low levels, and another displayed low C3 and
      C4 serum levels. Renal histology in the three cases showed type I
      membranoproliferative glomerulonephritis and hepatic cirrhosis in the liver
      biopsy. CONCLUSIONS: This report supports the association between chronic HCV
      infection and membranoproliferative glomerulonephritis. However, further studies
      are needed to establish more firmly the association as well as the mechanisms of
      pathogenesis and causality between them.

PMID- 7569361
TI  - [Occupational accidents and incidence of HIV infection and hepatitis B and C at a
      Mexican institution].
AB  - INTRODUCTION: The risk of developing parenterally transmitted infections in
      health-care personnel has become a challenge because of high costs, laboral
      incapacity and mortality, and social stigmatization. OBJECTIVES: To inform the
      incidence of occupational exposure in our institution, to determine the type of
      personnel affected and the circumstances of the injuries, and to assess the
      serologic follow-up of these employees. METHODS: The occupational injuries
      spontaneously reported to our infection control program from June 1987 to
      December 1993, were reviewed. Personnel categories, type of accident, instrument
      and circumstances of the injury, as well as serologic follow-up for hepatitis B
      virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
      infections, baseline and every three months during the first year were evaluated.
      RESULTS: In 6.5 years 260 injuries were registered in 240 workers. Two cases were
      registered in the second semester of 1987, 23 in 1988, 25 in 1989, 23 in 1990, 36
      in 1991, 90 in 1992, and 61 in 1993. Housekeeping and maintenance staff were
      mainly affected (32%), nursing staff in second place (27%), followed by senior
      medical students (20%). Eighty-eight percent were sharp injuries (20% considered
      deep injuries). Most of the injuries occurred after instrumental utilization:
      sharp devices disposed without the use of adequate containers (18%),
      inappropriate handling of sharp containers (14%) and recapping needles (11%); 36%
      of the injuries occurred during specific procedures. One HBV seroconversion
      occurred in 10 surface antigen exposures, one in nine exposures with an HCV
      contaminated source, and none in 54 accidents with HIV contamination.
      CONCLUSIONS: The increase in the annual incidence of occupational exposures is
      due most probably to more awareness to report the injuries. Eighty-eight percent
      were sharp injuries and at least 43% could have been prevented. Our main
      educational and preventive efforts should be directed to housekeeping staff,
      nursing staff, and medical students of our institution.

PMID- 7569364
TI  - [Comparison of instructions to authors of Mexican medical journals and the
      Vancouver requirements].
AB  - OBJECTIVE: To find out how much information of the Vancouver norms (VANNOR) are
      given to prospective authors in the instructions for authors (IFA) in some
      Mexican medical journals (MMJ). DESIGN: Prospective, cross sectional,
      descriptive, observational. MEASUREMENTS: To score the IFA in the MMJ published
      between 1989 and 1991. The scoring was done on the basis of presence in the IFA
      of the VANNOR characteristics grouped in categories (characteristics and
      presentation of the manuscript, title page, summary and keywords, text order and
      contents, references, tables, illustrations, and other instructions). A total
      score of 60 characteristics (grouped in nine categories) was obtained for each
      journal. Statistical differences as a function of VANNOR affiliation were
      investigated by means of Student's t test, chi-square, and exact Fisher tests
      using a 0.05 alpha level (two-tailed). RESULTS: 50 MMJ were included (21
      affiliated to VANNOR). No statistical difference was found for VANNOR affiliation
      and registration in bibliographic data bases. But statistically significant
      higher scores were found in the affiliated journals in 12 of 60 characteristics
      (three of nine categories) and in the total score. CONCLUSIONS: Independently of
      VANNOR affiliation, there were deficiencies in the IFA of all journals,
      particularly in instructions regarding the manuscript's contents. Possibly, some
      inadequacies in manuscripts might be prevented with IFA that comply more
      thoroughly with the VANNOR requirements.

PMID- 7569360
TI  - [Insulin transference in 198 patients from 6 Latin American countries].
AB  - A multicentric, comparative, single-blind, randomized, prospective study was
      designed to evaluate the efficacy and safety of the transference from animal
      source insulins to rDNA human insulin in Latinamerican insulin-requiring diabetic
      patients. All the patients were on animal insulin for at least two months before
      inclusion. The patients were evaluated at the beginning, and at two and six weeks
      after inclusion. A total 198 patients completed the study and were considered
      evaluable: 94 were assigned to the animal insulin group, and 104 to the human
      insulin group. There were no statistically significant baseline differences
      between groups. The only statistically significant difference, detected at the
      end of the study, was a reduction in fasting blood glucose level in the human
      insulin group (animal insulin 212 +/- 95.3 initial vs 193 +/- 78.3 mg/dL final, p
      = 0.18; human insulin 198 +/- 86.8 vs 169 +/- 71.7, p = 0.025). There were no
      statistically significant initial-final changes in the rest of the parameters
      evaluated although a trend of reduction in glycohemoglobin levels was observed in
      both groups. There were more episodes of mild hipoglycemia in the human insulin
      group, and only one episode of severe unwarned hypoglycemia in the same group. We
      conclude that the transference of insulins in Latinamerican diabetic patients is
      effective and reasonably safe (with a dose adjustment when the change is made).

PMID- 7569366
TI  - [Euthanasia: compulsory reflection].
AB  - Euthanasia should be considered one of the main philosophical topics of today's
      medical practice. In view of the technological advances in medicine, the economic
      pressure in the majority of our medical systems, and a deep alteration and
      modification in the patient-physician relationship, the status of some patients
      in their final days should be reconsidered. The increased awareness of the public
      about euthanasia and related topics (pain, assisted suicide, dying with dignity,
      etc.) suggests that a urgent dialogue between lay persons and physicians is
      needed.

PMID- 7569368
TI  - [The exclusion of cases].

PMID- 7569365
TI  - [Report of 2 cases with acquired von Willebrand disease and one with acquired
      hemophilia A].
AB  - We report three patients with acquired inhibitors against F VIII:C/F vW:Ag
      complex. Two patients had acquired hemophilia A. The three patients presented
      with bleeding diathesis. Case 1 was a 19 years old woman with Graves-Basedow
      disease; case 2 was a 40 years old woman with systemic lupus erythematosus of
      four years; and case 3 a 38 years old woman who had had rheumatoid arthritis for
      five years and was in her 3d month postpartum. The F VIII:C level was below 8
      U/dL in all cases. The F vW:Ag, ristocetin cofactor and platelet aggregation with
      ristocetin were diminished in the two cases with von Willebrand. Inhibitor to F
      VIII:C was 50, 38 and 20 Bethesda units, respectively, for cases 1, 2 and 3. The
      three patients showed clinical response to DDAVP and cryoprecipitates with
      partial response in laboratory tests. All patients responded to corticosteroid
      treatment, but immunosuppressive treatment was necessary in case 3.

PMID- 7569369
TI  - Treacher-Collins syndrome. Management of major and minor anomalies of the ear.
AB  - 12 patients suffering from a Treacher-Collins syndrome, or mandibulo-facial
      dysostosis, were operated on in the Nijmegen University Hospital between 1960 and
      1990. An early diagnosis is generally reached when there is a congenital atresia
      of the auditory canal. Auditory rehabilitation with a conventional prosthesis of
      the bone or a BAHA is preferable to surgical reconstruction. In minor cases,
      deafness must be screened as early as possible, with a bone hearing aid
      prosthesis. Surgical exploration can be performed at best as the age of 10, but
      the chances of success are less than those of other functional reconstructions
      because of the associated malformation.

PMID- 7569367
TI  - [Molecular structure of luminal diuretic receptors].
AB  - Since day to day sodium and water intake is more or less constant, the output by
      urinary sodium excretion is the key to maintain extracellular fluid volume within
      physiologic ranges. To achieve this goal, the kidneys ensure that most of the
      large quantities of filtered sodium are reabsorbed, a function that takes place
      in the proximal tubule, the loop of Henle and the distal tubule, and then the
      kidneys adjust the small amount of sodium that is excreted in urine in such a way
      that sodium balance is maintained. This adjustment occurs in the collecting duct.
      Three groups of diuretic-sensitive sodium transport mechanisms have been
      identified in the apical membranes of the distal nephron based on their different
      sensitivities to diuretics and requirements for chloride and potassium: 1) the
      sulfamoylbenzoic (or bumetanide)-sensitive Na+:K+:2CI- and Na+:CI- symporters in
      the thick ascending loop of Henle; 2) the benzothiadiazine (or thiazide)
      sensitive Na+:CI- cotransporter in the distal tubule; and 3) the amiloride
      sensitive Na+ channel in the collecting tubule. The inhibition of any one of
      these proteins by diuretics results in increased sodium urinary excretion.
      Recently, the use of molecular biology techniques, specially the functional
      expression cloning in Xenopus laevis oocytes, has led to the identification of
      cDNA's encoding members of the three groups of diuretic-sensitive transport
      proteins. The present paper reviews the primary structure and some aspects of the
      relationship between structure and function of these transporters as well as the
      new protein families emerging from these sequences. It also discusses the future
      implications of these discoveries on the physiology and pathophysiology of kidney
      disease and sodium retaining states.

PMID- 7569371
TI  - Endoscopy of the cerebellopontine angle.
AB  - The authors present their experience of 191 patients from June 1990 to December
      1993 with endoscopy of the cerbellopontine angle using a limited retrosigmoid
      approach. The advantages of endoscopy of the cerebellopontine angle are the
      simplicity and efficiency of the procedure, and less invasive surgery. The
      authors emphasize the importance of the endoscopic procedure: first in acoustic
      neuroma surgery to get more accurate information about the relationship between
      the tumour and the adjacent structures, and to control the lateral end of the
      internal auditory canal; second in hemifacial spasm or facial neuralgia surgery,
      intraoperative endoscopy is the key point giving a sure and safe way to recognize
      the offending vessels.

PMID- 7569370
TI  - Results of surgery for chronic otitis media: a 5-year study.
AB  - The results of 601 operations of the middle ear, including 50% of
      myringoplasties, performed between 1984 and 1989 are analysed. The standard
      Schuller's view radiography and the scanner are unreliable in determining the
      presence of a cholesteatoma recorded in 119 cases. The functional value of the
      Eustachian tube is important for taking the graft. On the other hand, there was
      no significant difference in the results depending on whether or not fibrin
      sealant was used, depending on the seat of the perforation, on the use of a
      homograft or of an autograft, and on age (before or after 14 years).

PMID- 7569372
TI  - [Widened retrolabyrinthine approach. Value in the surgery of acoustic neuroma
      with attempt of hearing preservation].
AB  - The retrolabyrinthine approach was described several years ago, however its use
      was restricted to functional surgery of the cerebellopontine angle. Its
      detractors reproach its narrowness. But a large approach to the cerbellopontine
      angle can be performed after an extended exposure of the posterior and middle
      fossa dura, and section of the endolymphatic sac. This approach was used in 5
      cases of acoustic neurinomas stage I and II, with normal hearing. Hearing
      preservation was obtained in 2 cases. We had deafness in 2 cases who had
      extensive tumor in the bottom of the internal auditory canal.

PMID- 7569374
TI  - Chondro-perichondrial connection in middle ear surgery.
AB  - Hearing conservation or gain are important parameters of tympanoplastic surgery.
      The frequency of this surgical procedure and the difficulty in obtaining tissues
      due to the increased risk of H.I.V. transfer has made the use of synthetic
      products somewhat more acceptable in contrast with the use of organic substances
      (homograft ossicles, bone, cartilage and perichondrium, etc...). We have been
      using tissues of the same patient (50), during a period of three years with a
      specimen constituted of cartilage and perichondrium designed as a "butterfly" and
      with very promising tympanoplastic and functional results. The tympanoplastic
      results were evaluated eighteen months postoperatively as follows: good: 86%,
      aural discharges that disappeared later 12%, perforations: 0%, keratin
      neoformations: 2%. Functional results were evaluated three years later as
      follows: gain more than 15 dB: 72%, same: 14%, worse: 14%.

PMID- 7569373
TI  - [Reliability of magnetic stimulation in the diagnosis of peripheral facial
      paralysis of idiopathic origin].
AB  - To evaluate the transcranial magnetic stimulation in the early diagnosis of
      traumatic facial palsy 7 patients with an incomplete Bell's palsy were examined.
      The clinical examination, electric stimulation and magnetic stimulation were
      performed daily from the 2nd day until the 6th day, at the 12th day and three
      months after onset of the disease. The mean latency of the surface potential of
      the orbicularis oculi muscle after electrical stimulation was 2.7 msec. On the
      healthy side the answer following transcranial ipsilateral cisternal magnetic
      stimulation was detectable after 6.8 msec. From the beginning no response could
      be recorded on the affected side. After clinical restitution of the Bell's palsy
      after three months there was still no response. On the other hand, the
      controlateral, cortical transcranial magnetic stimulation was not significantly
      reduced. In conclusion, the cisternal transcranial magnetic stimulation gives no
      further information beyond the clinical examination. The cisternal stimulation is
      useful, if a clinical examination is impossible e.g. in an unconscious patient
      after head injury.

PMID- 7569375
TI  - Experimental results concerning the reconstruction of the stapes superstructure
      with bioactive ceramics.
AB  - We examined the feasibility of rebuilding a stable stapes superstructure in the
      middle ear for a new articulated ossicular chain by using bioactive ceramic and
      glass ceramic in guinea pigs. The ceramic implants were placed on the stapes
      footplate without touching the tympanic membrane, thus protecting it against
      relative movements. The implants were removed together with the stapes footplate
      after six weeks, three and six months respectively. After six weeks, histological
      evidence of bony connections between all ceramic implants and the remnants of the
      crurae were found, being more pronounced after three and six months. We propose a
      new implant for the reconstruction of the stapes superstructure.

PMID- 7569377
TI  - [Subperichondrial undermining in the anterior scoring otoplasty technique
      (Stenstrom)].
AB  - In the otoplasty described by Stenstrom (1963), the scoring of the cartilage
      needs a very cautious undermining of the perichondrium. The electronic microscopy
      states very precisely the connexion between the perichondrium, the cartilage and
      the skin of the helix: there is a fibroblast coat (with a high density of fibers
      and connective tissue) which stays close to the cartilage strut: the author
      describes a special elevator which allows to undermine more safely this layer
      without wearing away the dermis.

PMID- 7569376
TI  - Preventive tympanoplasty in children: a new approach.
AB  - Chronic middle ear effusion with serous or mucus accumulation but without other
      associated tympanic and middle ear pathology can be successfully treated in many
      cases with myringotomy and ventilating tubes. But there are cases on which there
      are atrophic tympanic membrane areas with retraction into the middle ear,
      tympanic membrane adhesions to the long process of incus and incudo-stapedial
      joint with or without retraction toward the facial and tympanic recesses and
      shallow attic retraction pockets, which eventually will lead to cholesteatoma
      formation. All these minor anatomical distortions are usually asymptomatic, but
      with a potential to generate cholesteatomas throughout the years and cannot be
      corrected with a simple myringotomy and ventilation tube insertion. In these
      particular cases we have developed some types of tympanoplasty procedure that may
      prevent further progression to cholesteatoma formation. The purpose of this
      presentation is to describe these preventive tympanoplasty techniques and analyze
      the short and long term results in 68 surgical procedures.

PMID- 7569378
TI  - [Conservative otoplastic modelling: early operative indication].
AB  - The authors presents their philosophy and their experience in the field of
      otoplasty in young children. The modelling and conservative characteristic of the
      surgical procedure, used for over 6 years, allows surgery on children as young as
      3 years old. They detail the different operative steps underlining the rarity of
      the complications, the natural results achieved and the stability of these
      results with the child growth.

PMID- 7569379
TI  - Transtympanic gentamycin in the treatment of Meniere's disease.
AB  - Severe cases of Meniere's disease are successfully treated with ototoxic
      antibiotics. Gentamycin sulphate gives the best results. With the aid of a small
      syringe the drug is introduced into the external auditory canal 3-5 times per
      day. From there it is transported into the middle ear through a ventilating tube
      (Grommet) under slight pressure (Politzer bag). The liquid then penetrates the
      round and oval windows and influences inner-ear function. More than 90% of our
      patients in 25 years after therapy had no further attacks.

PMID- 7569381
TI  - Pediatric cochlear implants. Surgical aspects: the Nottingham pediatric cochlear
      implant programme.
AB  - The implantation of young children is widely accepted as a means of
      rehabilitating profoundly/totally deaf children. This paper will review the
      surgical aspects of implanting young children based on the first 50 children
      implanted in the Nottingham paediatric cochlear implant programme. Having
      thoroughly counselled the children's parents, the child is operated on under
      prophylactic antibiotic cover. The incision (extended endaural) is made directly
      down to bone and a full-thickness flap is elevated. Meticulous attention is paid
      to haemostasis. The steps involved in posterior tympanotomy, cochleostomy and
      implant insertion, often in the presence of osteogenesis, will be described.
      Electrophysiological testing is done systematically peroperatively. Surgical
      complications were few. There was no cases of facial weakness, haematoma, implant
      extrusion or infection. One patient, whose implant was laid in an extracochlear
      gutter, developed pain on electrical stimulation and was explanted. Another
      patient developed a retraction pocket cholesteatoma. These few complications are
      far outweighed by the overwhelming benefits accrued from implantation.

PMID- 7569380
TI  - Effects of antibiotic solutions (ciprofloxacin and trimethoprim +
      sulfamethoxazole) on rabbit tympanic membrane.
AB  - This study was designed to assess morphological changes in the rabbit tympanic
      membrane after Ciprofloxacin and Trimethoprim + Sulphamethoxazole had been
      instilled as a single dose into the middle ear cavities of 24 rabbits. At
      different times the rabbits were decapitated and the lesions which occurred on
      the tympanic membrane were studied histopathologically. Our results indicate that
      in the Ciprofloxacin group reactive inflammatory changes are reversible as in the
      Trimethoprim + Sulphamethoxazole group.

PMID- 7569382
TI  - Bell's palsy and visualization of the facial nerve by MRI.
AB  - A group of patients complaining of facial nerve palsy (Bell's palsy) were
      evaluated with MRI using a 0.5 unit and high resolution T1-weighted images, in
      order to evaluate the efficacy of Gd-DTPA enhancement in depicting the degree of
      nerve damage: MRI examination was performed within 24 hours to two weeks after
      the onset of palsy. The authors describe the results obtained from the analysis
      of 11 cases of Bell's palsy, discussing the prognostic and clinical significance.

PMID- 7569383
TI  - Comparison of postoperative results in suspected and confirmed cases of
      perilymphatic fistula.
AB  - Perilymphatic fistula is suspected on clinical symptoms, but must be confirmed by
      surgery. Exploratory tympanotomy was realized in 38 patients, presenting one or
      several symptoms of perilymphatic fistula. A leak was observed in 23 patients
      (61%). When a leak was not observed, the oval and round windows were filled with
      connective tissue. Preoperative and post-operative symptoms were compared in
      patients with or without leak: there was not significant difference between the
      two groups of patients. 63% of patients presenting fluctuant or sensorineural
      hearing loss improved or stabilized hearing after surgery. One patient,
      presenting a post-traumatic total deafness due to round window rupture, was
      immediately operated on, and recovered normal hearing. 84% of patients with
      vertigo or dizziness improved after surgery. The authors conclude that
      exploratory tympanotomy should be widely proposed when a perilymphatic fistula is
      suspected. Oval and round window should be grafted with connective tissue even if
      a leak is not observed.

PMID- 7569384
TI  - [Current imaging of vasculo-neural conflicts in the cerebellopontine angle].
AB  - To demonstrate the high sensitivity of high definition MRI and particularly
      "Constructive Interference in Steay State" (Ciss) imaging sequence, in depicting
      neurovascular conflicts in the CP angle cistern, cisternographic imaging and high
      definition T1 weighed (Turbo flash), contrast enhanced imaging were used to
      investigate hemifacial spasm (72 patients) and tinnitus with abnormal BER (5
      patients). The study was complemented with Angio MR in 25 patients. The results
      were compared with findings in a control group of 200 patients, and with the
      surgical observations in 57 operated cases. In hemifacial spasm, the morphology
      of the neurovascular conflict was determined, as well as the site of compression
      (lateral medullary fossa 38 cases; nerve 9; both 15 cases), and the vessel
      involved (VA 25 cases; PICA 16 cases; AICA 10 cases; VA and PICA 8 cases; VA and
      AICA 3 cases; lateral medullary vein 1 case). In tinnitus (5 cases), the AICA was
      involved in every case in the IAM. Among 57 operated cases, only one false
      negative was observed. In the asymptomatic control group, a nerovascular conflict
      was observed in 3, 5% of the cases only. CONCLUSION: CISS imaging is the single
      most efficient technique, but the combined used of the 3 types of imaging brings
      the highest diagnostic efficiency, for identifying a neurovascular conflict in
      the CPA cistern.

PMID- 7569385
TI  - [Experimental surgery of the facial nerve. Evaluation of the intraperitoneal use
      of exogenous gangliosides].
AB  - Compression and section of the facial nerve were performed in 48 rats in order to
      study the anatomopathological alterations occurring after daily intraperitoneal
      injections of 100 mg of exogenous gangliosides (Sinaxial) for 45, 90, 180 days.
      In groups submitted to nerve compression, the histopathological changes were
      discrete and in the 180-day subgroups the nerve was practically normal. In
      animals submitted to section and neurorrhaphy there was formation of an
      amputation neuroma, a granuloma around the suture, axonal unstructuration and
      inter and perineural fibrosis. No significant differences were observed between
      the groups submitted or not to injection of exogenous gangliosides, indicating
      that the major factors involved in the quality of nerve regeneration were the
      technique and the formation of fibrosis and of an amputation neuroma.

PMID- 7569387
TI  - [Relations between vasculotensional disease, sudden deafness and benign
      paroxysmal postural vertigo: value of anticochlear antibodies].
AB  - Some vasculotensional diseases may be associated, at a certain point of their
      evolution, with occurrences of sudden deafness or of benign paroxysmal positional
      vertigo. It seems that the efficiency of the treatments of sudden deafness and
      benign paroxysmal positional vertigo is not modified by those associations of
      pathologies. On the other side, the search for anticochlear antibodies gives a
      positive result in 45% of the vasculotensional diseases. When the
      vasculotensional disease is associated with sudden deafness, this percentage
      increases. On the contrary, it is lower when the vasculotensional disease is
      associated with benign paroxysmal positional vertigo. The presence of
      anticochlear antibodies may lead to a corticotherapy in case of failure of the
      classical treatments.

PMID- 7569388
TI  - [Goode's transtympanic drains. Indications and complications].
AB  - The authors present a statistical record of the complications encountered in the
      use of 151 Goode transtympanic aerators used in their department between 1981 and
      1991. The frequency of the problems encountered, in particular residual tympanic
      perforations, is discussed in detail, to assess the soundness of the various
      indications.

PMID- 7569386
TI  - [Management of post-traumatic facial paralysis. Apropos of 83 cases].
AB  - The authors report a series of 83 cases of post-traumatic facial paralysis. This
      study shows that 65% of paralysis are related to traffic accidents. In 76% of the
      cases, the deficit is immediate. The initial clinical evaluation evidences a
      majority of grade V (68%). The auditive impairment is related in 48% of the cases
      to transmission deafness, in 41% of the cases, there is impairment of the inner
      ear; lastly for 11% of the patients, hearing is preserved. The electromyography
      analyses the gravity of the facial nerve impairment: in 47 cases, clear-cut
      denervation can be noted. Lastly, for 11% of the patients, hearing is preserved.
      The electromyography analyses the gravity of the facial nerve impairment: in 47
      cases clear cut denervation can be noted. Lastly, the electromyography is
      supplemented by a scan of the temporal bone which defines the type of fracture.
      Out of 83 patients, 14 labyrinthine fractures were found. Based on the various
      tests, the therapeutic decision led to 31 medical treatments and 52 surgical
      procedures. The latter were performed within a 15-day to 2-month time period for
      83% of the patients. The type of surgery depends on the supposed lesional site:
      31 mixed approaches (middle fossa and transmastoidal), 15 transmastoidal
      approaches and 6 tranlabyrinthine approaches. Impairment of the geniculate
      ganglion is quite frequent. Most often, an edema or a confused aspect is found.
      Sections are rarer (7 cases). The results are excellent for impairment treated
      non-surgically. In the surgically treated patients, prognosis is more uncertain,
      especially if a nerve graft is required.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569389
TI  - [Bacteriology of maxillary sinusitis among members of the 11th parachutist unit].
AB  - When sinusoscopic examinations of chronic maxillary are made, bacteriological
      samples are the most often carried out. We report results of thirty one cases
      among young soldiers 19 to 23 years old. Our bacteriological results are similar
      to those reported in literature. A bibliographic study reminds the recent
      bacteriological findings according to countries or type of patients where
      pathogen germs were researched.

PMID- 7569390
TI  - [Complications of endonasal microsurgery].
AB  - Endonasal microsurgery, which has widely proved its efficacy, is not free of
      complications. They can be due to the technical act itself. In this case they
      result of surgery mistake and they induce an effraction of the operatory cavity
      walls. They can also be due to excessive healing of the nasal mucosa. Then they
      represent the real cause of failure in this type of surgery. The authors present
      their experience that they compare with similar cases of the literature.

PMID- 7569391
TI  - [Cervico-facial cellulitis of oral and dental origin: study of 26 cases at the
      Lome University Hospital].
AB  - The authors report 26 cases of cervico-facial cellulitis of mouth and dental
      origin. They highlight the severity of those affections. The original entry is
      dental caries in 88.4% of cases. Adequate treatment consisting of a surgical
      drainage, a suppression of the original entry and antibiotherapy combining a
      penicillin, an aminoglycosid and metronidazol. Preventive therapeutic measures
      are prescribed.

PMID- 7569393
TI  - [An uncommon site of hydatid cyst].
AB  - The authors report on a case of a cervical hydatid cyst revealed by an isolated
      subangulomaxillary tumefaction. They stress the scarcity of this localization,
      the definitive diagnosis of which is obtained only with an exploratory and
      curative cervicotomy.

PMID- 7569394
TI  - [Papillary carcinoma on the site of a thyroglossal duct cyst: report of a case].
AB  - The thyroglossal tractus cysts are uncommonly the site of malignant tumors. The
      detection of such located cancer is always histologic. No clinical sign makes
      thought the malignant degeneration of a thyroglossal tractus cyst. The authors
      report here one case of papillary carcinoma of thyroidal origin developed on
      thyroglossal tractus cyst. At total thyroidectomy which was carried out three
      weeks later, a thyroid papillary carcinoma was found to be present. So, we think
      that it is interesting to do a literature review about the malignant degeneration
      of these cysts, based mainly on relationship between this tumor and an eventual
      lesion of the thyroid body. The therapeutical management of cancers of cysts is
      solely surgical and in general the prognosis of these cancers is excellent.

PMID- 7569395
TI  - [Thyroid metastases of Grawitz tumors: apropos of a case].
AB  - Secondary localisations of malignant tumors to the ENT areas are rare. One case
      of renal adenocarcinoma metastasis to the thyroid has been followed in our
      department. After a quick recall of the clinical story, we will try to point out
      the epidemiological and physiopathological specificities of this localisation and
      to emphasize its therapeutic difficulties.

PMID- 7569396
TI  - [Rhinolithiasis].
AB  - This article presents a case of rhinolithiasis in a 16-year old girl, which
      evolved over a period of 8 years. The symptoms were an obstruction of the right
      nasal fossa, fetidness, and a chronic infection resulting in atrophic changes.
      The rhilolith was removed by the anterior approach, without damaging the
      neighbouring structures. The histopathological examination revealed the presence
      of an inorganic nucleus (latex). The patient had no memory of having introduced
      this foreign body.

PMID- 7569397
TI  - [Rhinolithiasis: apropos of 3 cases].
AB  - Rhinolithiasis is not an everyday complaint. It is often discovered fortuitously.
      A thorough clinical examination will provide the diagnosis and the main lines for
      treatment. This study is illustrated by 3 clinical observations.

PMID- 7569392
TI  - [Thyroid surgery: risks and complications. Apropos of 134 cases].
AB  - From a retrospective covering 134 patients operated from the thyroid gland, the
      authors have tempted, over at least a year's survey, to clarify the incidence of
      the main post-operative complications. Recurrent laryngeal nerve paralysis and
      permanent hypoparathyroidism are the two major risks, with a respective
      percentage of 2.25% and 7.4%. After a general review of publications the
      discussion is focused on the etiology of the different complications already
      found and on the possible means to avoid them or, at least, to minimize them.

PMID- 7569399
TI  - [Cavernous hemangioma of the internal auditory canal. Apropos of a case].
AB  - A case of cavernous hemangioma in the internal auditory canal was reported. There
      were no specific symptoms or physical or neurotological findings to differentiate
      from acoustic neuroma. The clinical and surgical aspects of this rare tumor were
      reviewed and discussed.

PMID- 7569398
TI  - [Neurofibroma of the recurrent nerve: apropos of a case].
AB  - A case of solitary benign neurofibroma of the recurrent laryngeal nerve is
      presented. The preoperative diagnosis was in favour of a thyroid cancer. The
      discovery of this benign tumour leads to discuss the malignancy criteria of a
      cold nodule. The recurrential paralysis is an evidence of malignancy in only
      about 80% of cases. The surgical operation is the best treatment because it
      allows the histology that asserts the benignancy of the lesion. The review of the
      literature confirms the exceptional nature of this tumour. The respective
      histology of neurofibromas is finally briefly recalled.

PMID- 7569400
TI  - Granulomatous vasculitis.
AB  - Vasculitides are classified by the size of the vessel involved and by the nature
      of the inflammatory process. Pulmonary granulomatous vasculitis encompasses
      several entities that are in general characterized by granulomatous inflammation,
      extensive necrosis, and a variegated cellular infiltrate. Wegener's
      granulomatosis is a prototype of granulomatous vasculitis and is a disease of
      unknown etiology that often involves the upper respiratory tract, the lower
      respiratory tract, and the kidneys. Some of the entities initially classified as
      pulmonary granulomatous vasculitis have subsequently been found to represent
      other entities; specifically, lymphomas (lymphomatoid granulomatosis) and part of
      the spectrum of bronchopulmonary aspergillosis (bronchocentric granulomatosis).
      In addition, it is recognized that certain infectious conditions, specifically
      the necrotizing inflammatory processes caused by fungi and mycobacteria, can show
      granulomatous vasculitis and can be confused with Wegener's granulomatosis. The
      mechanism by which pulmonary granulomatous vasculitis occurs is not well
      understood, although is thought to have an immunologic basis. A great deal of
      data has been accumulated concerning antineutrophil cytoplasmic autoantibodies
      and the role that these antibodies might play in the development of these
      conditions.

PMID- 7569404
TI  - Hypersensitivity pneumonitis: a noninfectious granulomatosis.
AB  - Hypersensitivity pneumonitis or extrinsic allergic alveolitis is an
      immunologically mediated lung disease caused by repeated inhalations of organic
      antigens. The basic histological lesion consists of a diffuse mononuclear cell
      infiltration of alveolar wall, alveoli, terminal bronchioles, and neighboring
      interstitium. The inflammation is often followed by granulomas, which then may
      progress to fibrosis. Unlike other infectious and noninfectious granulomatous
      disorders, hypersensitivity pneumonitis is limited to the lung. The disease
      occurs more frequently in men than in women and children. The acute form of
      hypersensitivity pneumonitis, characterized by fever, chills, myalgias, cough,
      and dyspnea, may be confused with acute pneumonitis. Although there is no single
      radiological, physiological, or immunologic test specific for hypersensitivity
      pneumonitis, the diagnosis can often be suspected on the basis of a compatible
      temporal relationship between pulmonary symptoms and a history of environmental
      or occupational exposure. Once the diagnosis is suspected, the presence of serum
      precipitating antibodies (immunoglobulin [lg] G), suppressor cytotoxic
      lymphocytosis in bronchoalveolar lavage (BAL) fluid, and granulomatous alveolitis
      in lung biopsy specimens is extremely helpful in confirming the diagnosis. For
      patients in whom the diagnosis is confirmed, avoidance of the causative antigen
      is the best therapy, although corticosteroids are used to suppress inflammation.
      Once the fibrosis has developed, the patient may gradually develop respiratory
      failure or cor pulmonale, possibly resulting in death.

PMID- 7569401
TI  - Bronchiolitis obliterans organizing pneumonia.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is increasingly recognized
      as an important cause of diffuse infiltrative lung disease. It is a diagnostic
      consideration in patients with a febrile flu-like illness of a few weeks'
      duration and a roentgenogram showing bilateral patchy infiltrates that are not
      responsive to a typical course of antibiotics. It is defined as granulated tissue
      plugs within lumens of small airways that extend into alveolar ducts and alveoli.
      Clinically, a flu-like illness, cough, and crackles are common. Pulmonary
      function studies of patients show a decreased vital capacity, normal flow rates
      (except in smokers), and a decreased diffusing capacity. It is generally
      idiopathic, but it may occur during the resolution of a viral or mycoplasma
      pneumonia. It is also associated with a variety of systemic illnesses and
      clinical settings. These include the connective tissue disorders, antineoplastic
      and other drugs, and immunological disorders, as well as bone marrow and lung
      transplantation. There are numerous related disorders, including human
      immunodeficiency virus infection, radiation therapy, thyroiditis, and alcoholic
      cirrhosis. In idiopathic BOOP, complete resolution occurs in 65% to 85% of
      patients treated with corticosteroid therapy. This type of therapy is often
      effective in patients with associated systemic disorders or in other clinical
      settings, but there may be limited or no response in patients with
      dermatomyositis, immunosuppression, or interstitial opacities at the lung bases.
      Respiratory failure leading to death may occur in 5% of patients. It is important
      to add BOOP to the differential diagnosis of febrile, noninfectious illnesses
      that are mimics of pneumonia.

PMID- 7569403
TI  - Drug-induced pulmonary disease.
AB  - In any febrile patient with an unexplained chest radiographic abnormality who is
      on medication, the possibility that the observed abnormality is drug-induced must
      be kept in mind. This is a significant problem in the immunocompromised host
      receiving chemotherapeutic agents because these agents are almost always
      associated with a fever, although the fever may not be daily and is usually not
      associated with sweats or shaking chills. The infiltrate initially can be quite
      focal and then unilateral, exhibiting diffuse lung disease before becoming
      bilateral. Thus, in its early stages, it mimics an infectious process.
      Unfortunately there is no diagnostic test to rule in drug-induced lung disease
      because it really is a condition of exclusion. Lung biopsy may be required to
      exclude other causes. It is also important to remember that drugs may be a factor
      in the immunocompetent patient who is taking medication and has a fever. It is
      important for the clinician to be aware of which drugs can do this.

PMID- 7569402
TI  - Collagen vascular diseases.
AB  - Systemic lupus erythematosus, polymyositis/dermatomyositis, connective tissue
      disease, and polyarteritis nodosa are the collagen vascular diseases (CVDs) most
      likely to mimic pneumonia. All can be associated with an acute illness
      characterized by fever, cough, dyspnea, pleural symptoms, and an abnormal chest
      roentgenogram. Recognition of the CVD-associated pulmonary process requires
      sophisticated serological testing and chemical pleural fluid analysis coupled
      with the exclusion of pulmonary infection and pulmonary embolization. This review
      emphasizes the clinical characteristics of these CVDs, the diagnostic tests most
      helpful in recognizing them, and the differential diagnosis of pleuroparenchymal
      disorders that occur in these patients.

PMID- 7569405
TI  - Inductive interactions during kidney development.
AB  - The conversion of intermediate mesoderm into renal tubular structures occurs
      throughout embryonic development from the formation of the nephric duct through
      to the generation of metanephric nephrons. Studies using an in vitro model system
      of renal epithelial morphogenesis indicate that the signals mediating
      tubulogenesis rescue intermediate mesoderm from programmed cell death, trigger
      spindle-shaped mesodermal cells to differentiate into epithelia, and lastly
      promote epithelial cell diversification and segmented tubule assembly. Recent
      data indicate that members of the Wnt family of developmental regulatory genes
      play an important role in the signaling pathway mediating renal epithelial
      morphogenesis.

PMID- 7569406
TI  - Transcription factors in renal development: the WT1 and Pax-2 story.
AB  - The development of a complex, multicellular organ, such as the kidney, from two
      embryonic progenitor tissues requires the activation and suppression of
      transcription factors that regulate tissue and cell type-specific gene
      expression. From areas as diverse as fruit fly development and human cancer
      genetics, a number of important genes have been identified that help to
      orchestrate the early events of renal epithelium induction and differentiation.
      The Wilms' tumor-suppressor gene WT1 is critical for regulating the early
      response of the kidney mesenchyme to induction and may play multiple roles during
      the course of renal epithelial cell development and tumor formation. The Pax-2
      gene is activated in the mesenchyme after induction and is necessary for
      condensation and perhaps proliferation of the induced cells. How these two
      important gene products exert their effects will be discussed in light of recent
      evidence on DNA binding, transcription repression, and protein interactions.

PMID- 7569407
TI  - Epithelial cell polarity: new perspectives.
AB  - All epithelial cells possess two distinct plasma membrane domains. The apical and
      basolateral domains differ in protein and lipid composition, and this allows the
      cell to perform a variety of vectorial functions. Structures involved in
      generating and maintaining these distinct membrane domains include the tight
      junction, which serves to restrict lateral diffusion within the membrane, and the
      cortical cytoskeleton, which can selectively bind and retain transmembrane
      proteins at a particular surface. A major means to generating membrane asymmetry
      lies in the ability of the cell to sort apical and basolateral proteins and
      target them to appropriate destinations. This sorting occurs predominantly at two
      intracellular sites: the trans-Golgi network, and the basolateral endosome.
      Constitutive protein traffic in epithelial cells has recently been shown to be
      regulated via classical signal transduction pathways involving heterotrimeric G
      proteins and protein kinases. The diversion of apical and basolateral proteins
      into specific pathways can be mediated by signals contained within these
      proteins. Apical sorting information is thought to be localized in the luminal
      domain of transmembrane proteins, and in the case of proteins anchored to the
      membrane via a GPI anchor, apical sorting information is provided by the lipid
      moiety. In contrast, basolateral signals have been identified in the cytoplasmic
      domain of transmembrane proteins. Shared similarities between basolateral signals
      and those required for endocytosis have suggested that these two sorting
      processes are mechanistically related.

PMID- 7569408
TI  - The role of the cytoskeleton in renal development.
AB  - The cytoskeleton is comprised of three separate filament networks: microtubules,
      microfilaments, and intermediate filaments. Collectively, these networks help
      establish and maintain the structural features of renal epithelial cells. During
      renal development, the cytoskeleton of the metanephric mesenchyme is extensively
      reorganized in order to create the cytoarchitectural elements that distinguish
      tubuloepithelial cells. This reorganization is coordinated with the formation of
      cell-cell contacts and cell-extracellular matrix interactions that are necessary
      to complete the developmental program. The actin cytoskeleton, microtubule
      network, and intermediate filament network all contribute to the development of
      polarity in the renal epithelial cells. The microtubule network determines the
      apical-basal axis of the cell. The actin cytoskeleton integrates topographic
      contacts between the cells and extracellular matrix. The tight junction and
      microvilli are subcellular structures that are associated with or comprised of
      actin filaments. Intermediate filament composition changes during the embryonic
      transition from metanephric mesenchyme to tubular epithelial cells. This review
      will describe the cell biology of the cytoskeletal elements in epithelial cells
      and the changes in cytoskeleton that accompany the formation of differentiated
      epithelial cells.

PMID- 7569410
TI  - Origin of the glomerular vasculature in the developing kidney.
AB  - Mechanisms regulating the establishment of the glomerular endothelium and
      mesangium during glomerulogenesis are not understood. In this article, we discuss
      two different blood vessel growth processes: vasculogenesis and angiogenesis,
      with particular attention on how these processes might operate in the developing
      kidney. Results from metanephric organ cultures and interspecies grafts are also
      interpreted with an emphasis on generation of the renal microvasculature. Among
      the several growth factors identified in the metanephros, many (eg, fibroblast
      growth factor [FGF], vascular endothelial growth factor [VEGF], platelet-derived
      growth factor [PDGF], epidermal growth factor/transforming growth factor-alpha
      [EGF/TGF-alpha], hepatocyte growth factor/scatter factor [HGF/SF], and
      insulinlike growth factor [IGF]) have angiogenic properties, and these are
      discussed in relation to formation of the glomerulus. How extracellular matrices
      and proteases might be involved in vascularization are also considered.

PMID- 7569411
TI  - Development of the tubular nephron.
AB  - The renal tubule derives from two embryological structures: the metanephric
      mesenchyme and the ureteric bud. Tubulogenesis occurs in these two structures
      through somewhat different processes. The proximal through distal tubule of the
      nephron arises through compaction of previously unpolarized cells derived from
      the metanephric mesenchyme, whereas the collecting system arises through
      branching morphogenesis of an existing epithelial structure (the ureteric bud).
      Recent evidence from in vitro models using renal epithelial cells that undergo
      tubulogenesis and branching morphogenesis in three-dimensional collagen gels have
      shed light on the likely roles of growth factors, the extracellular matrix, and
      matrix-degrading proteinases in renal development. Differential effects of
      several growth factors (hepatocyte growth factor [HGF], transforming growth
      factor-alpha and -beta [TGF-alpha, TGF-beta], and epidermal growth factor [EGF])
      suggest a mechanism for regulating the degree of tubule formation and branching
      events during collecting system development. Another model, the MDCK cell
      "calcium switch," is useful for studying the assembly of intercellular junctions
      and development of apical-basolateral polarity such as occurs during compaction
      of mesenchymally derived cells in developing renal tubules. Recent work with this
      model suggests that the assembly of intercellular junctions is regulated by
      classical signaling mechanisms including those involving intracellular calcium
      and calcium-dependent protein kinases. Together with organ culture studies of the
      embryonic kidney and analysis of genetically engineered mice, these models should
      allow dissection of specific molecular pathways in tubulogenesis.

PMID- 7569409
TI  - Growth factors in renal development.
AB  - The formation of all organs during embryogenesis, including the kidney, is
      dependent on the timed and sequential expression of a number of polypeptide
      growth factors. Synthesis and actions of one or more members of the insulinlike
      growth factor (IGF), epidermal growth factor/transforming growth factor-alpha
      (EGF/TGF-alpha), transforming growth factor-beta (TGF-beta), platelet-derived
      growth factor (PDGF), fibroblast growth factor (FGF), hepatocyte growth factor
      (HGF), and nerve growth factor (NGF) families have been characterized in the
      developing metanephric kidney. Studies originating from a number of laboratories
      have defined the localization of growth factor mRNAs, receptors and peptides,
      have delineated patterns of growth factor synthesis, have established the growth
      factor-dependency of embryonic kidney development, and have identified
      abnormalities of growth factor-expression as potentially causative of aberrancies
      in metanephrogenesis. The results of these investigations are summarized in this
      review.

PMID- 7569413
TI  - Cystic maldevelopment of the kidney.
AB  - Cystic maldevelopment of the kidney can occur when the normal processes of
      nephrogenesis are disrupted. The result is formation and enlargement of fluid
      filled cysts instead of normal renal tubules. Several human disease states are
      associated with the development of renal cysts. Events triggered by genetic
      mutation or environmental insult probably lead to the combination of factors
      believed to stimulate cyst formation and enlargement, including epithelial
      hyperplasia, abnormal protein sorting, altered fluid transport, and abnormal
      extracellular matrix:cell interactions. A precise delineation of the cellular
      pathophysiology of renal cystic maldevelopment has the potential to do the
      following: (1) focus genetic investigation on specific "cystic" candidate genes;
      (2) provide models for the definitive identification of such candidate genes; and
      (3) provide key targets for immunotherapy or pharmacotherapy designed to prevent
      renal cyst formation and progressive enlargement.

PMID- 7569412
TI  - Renal epithelial cell hyperplasia and hypertrophy.
AB  - Renal epithelial cells that are part of an intact tubule epithelium divide at a
      very slow rate. However, in response to physiological signals or pathological
      processes, their rate of growth can rapidly increase. In these situations, the
      growth response can be hyperplasic (an increase in cell number) and/or
      hypertrophic (an increase in cell size). This article reviews our current
      understanding of the signaling pathways involved in renal epithelial cell
      hyperplasia and hypertrophy. Hyperplasia involves an initiating mitogenic
      stimulus, followed by the synthesis of a number of proteins that regulate a
      cascade of events governing progression through each of the phases of the cell
      cycle (G1, S, G2, and M phases). Renal epithelial cell hypertrophy can occur by
      cell cycle-dependent or -independent mechanisms. Cell cycle-dependent hypertrophy
      involves signals that cause cells to enter the first phase of the cell cycle
      (G1), but become arrested before leaving this phase. The consequence of these two
      sequential events is cell growth without DNA replication and, thus, cell
      hypertrophy. pRB plays a key role is the development of this form of hypertrophy.
      Cell cycle-independent hypertrophy probably involves inhibition of pH-sensitive
      lysosomal enzymes, leading to decreased protein degradation, and consequently an
      increase in cell protein content and cell hypertrophy.

PMID- 7569414
TI  - Effects of ureteral obstruction on renal growth.
AB  - Renal insufficiency due to congenital obstructive nephropathy is a consequence of
      arrested or abnormal renal growth. A number of experimental studies have shown
      that the younger the age at the time of unilateral ureteral obstruction (UUO),
      the more severe the growth impairment of the ipsilateral kidney, and the greater
      the compensatory growth of the opposite kidney ("counterbalance"). Urinary
      obstruction in early fetal life results in renal dysplasia and a decrease in the
      number of functioning nephrons. The renin-angiotensin system is highly activated
      in early development, and UUO further increases this activity, resulting in
      vasoconstriction and glomerular contraction. Long-term UUO also causes
      progressive interstitial fibrosis, which presumably contributes to arrested
      growth of the kidney. This may result from excessive deposition of extracellular
      matrix stimulated by increased expression of transforming growth factor-beta 1.
      Neonatal UUO delays the expression of epidermal growth factor, and prolongs the
      expression of peritubular alpha smooth muscle actin, suggesting that renal
      maturation is delayed by UUO. Renal apoptosis is increased by UUO, which may
      contribute to the reduced DNA content of the neonatal obstructed kidney. Renal
      expression of clusterin, a glycoprotein associated with cell adhesion and
      protection from apoptosis, is increased by ipsilateral UUO, and also presumably
      modulates renal growth. Thus, renal growth and development are impaired by UUO
      through complex interactions between regulators of cell proliferation, cell
      destruction, and extracellular matrix.

PMID- 7569415
TI  - Clinical impact and biological basis of renal malformations.
AB  - Little is understood regarding the pathogenesis of human renal malformations.
      These disorders include the total absence of renal tissue (or renal aplasia) and
      organs that contain undifferentiated kidney cells (or renal dysplasia). Various
      lines of evidence from animal studies suggest that kidney malformations can be
      generated by (1) the mutation of master genes expressed during nephrogenesis, (2)
      the prenatal obstruction of the urinary tract, and (3) also by teratogens.
      Although the majority of human renal malformations occur sporadically, some are
      familial and would thus seem to have a genetic basis. It is possible but unproven
      that some sporadic cases may represent new mutations. A understanding of the
      biology of normal and abnormal nephrogenesis will ultimately lead to earlier
      diagnoses of renal malformations and will make it possible to conceive of
      therapeutic strategies that may enhance the differentiation and survival of
      metanephric precursor cells.

PMID- 7569416
TI  - [Kaposi disease].

PMID- 7569419
TI  - [Genetic predisposition to cancer].
AB  - This review focuses on the genetics of inborn predisposition to the development
      of cancer. The gene defects responsible for the majority of the most common
      syndromes of inherited predisposition to cancer have been deciphered during the
      last five years. These discoveries have shown that the genetics of most of these
      inherited forms of cancer is remarkably simple: the mechanism underlying the risk
      of cancer is precisely the one proposed by Knudson to explain the inherited forms
      of retinoblastoma. Only a small minority of the cancers are imputable to
      inherited mutations causing a very high risk of cancer. However, low penetrance
      susceptibility genes, mainly acting as environmental risk modifiers, are probably
      involved in the development of the majority of cancers. As much as possible, we
      will consider the immediate and long term possible repercussions on everyday
      medical practice of these advances in basic understanding of genetic cancer
      risks.

PMID- 7569420
TI  - [Bacteriological diagnosis of tuberculosis: current hieratic classification of
      methods].
AB  - To assure the diagnosis of tuberculosis, one needs the observation, the isolation
      and the identification of the causative agent Mycobacterium tuberculosis. In this
      approach, the microscopic exam occurs as a fast but neither sensitive or specific
      test. The isolation on solid media is slow and needs more than three weeks before
      becoming positive. Nevertheless, it is a sensitive and specific one. The
      identification of the isolated strain and the study of sensitivity to antibiotic
      agents require an equal delay. Then, 2 months are necessary to achieve the
      analysis. The AIDS epidemic with the increase of opportunistic mycobacterial
      diseases, and the unexpected arrival of resistant Mycobacteria is creating as a
      difficult therapeutic problem. The cultivation in liquid media with the
      radiometric method (Bactec) shortens the time of culture by half. The genomic
      amplification assay has been hopeful because it allowed results in 2 days.
      However, some technical difficulties happen when the test is conducted and it is
      less sensitive than the isolation process. The hierarchical classification of the
      laboratory useful process to establish the diagnosis of tuberculosis disease
      remains the microscopic observation of the bacilli and their isolation. Today,
      the use of PCR alone does not assure the diagnosis of tuberculosis, however it
      may be used as a additional diagnostic test.

PMID- 7569417
TI  - [Neurologic manifestations of Lyme disease. Apropos of 25 cases].
AB  - We studied retrospectively the cases of neurological forms of Lyme disease
      observed in two internal and two neurological departments from 1986 till 1993.
      Twenty five cases have been collected among 15 men and ten women whose mean age
      was 61 years. Tick bites were previously noticed in 11 cases. Erythema chronicum
      migrans (ECM) was mentioned in 16 cases mostly on lower limbs. The mean time
      between ECM and the onset of neurological symptoms was less than 1 month in 11
      cases, 2 months in three cases, and 6 months in two cases. Neurological
      abnormalities were often associated in the same patient. Hyperalgic radiculitis
      (n = 16), mainly noticed in the ECM territory (n = 10) was only sensitive in six
      cases and associated with motor deficit in ten. Atypical polyradiculoneuritis was
      achieved in six cases. Clinical (n = 5) or biological (n = 22) meningitis could
      occur: CSF was clear with pleiocytosis (132 per mm3), mainly lymphocytic, and
      hyperproteinorachia (1.2 g/l) with normoglycorachia. An increase of the CSF
      immunoglobulins G with oligoclonal fragmentation was noticed in 11 cases. Cranial
      neuropathy was frequent: VII (n = 8), VI (n = 2), III, IV, VIII (n = 1).
      Encephalitis (with white matter demyelination) resolved partially in two cases.
      Diagnosis was always confirmed by Borrelia burgdorferi serology (indirect
      immunofluorescence) with a significant increase of the antibodies titer (n = 17)
      or a CSF titer > 1/4 (n = 11). Syphilitic serology was always negative. All
      patients were treated with parenteral beta lactamins and four with
      corticosteroids. Outcome was favorable in 20 patients with incomplete resolution
      of neurological symptoms in two patients.

PMID- 7569418
TI  - [Acute drug-induced agranulocytosis. Clinical study apropos of 30 patients and
      evolution of etiologies over 2 decades].
AB  - Between 1982 and 1993, 30 patients were treated for drug-induced agranulocytosis.
      They did not receive cytotoxic chemotherapy nor radiotherapy during the past 6
      months. There is a higher incidence in women (21 females, nine males). Mean age
      is 59.3 years old. The drug could be found in 25 cases including noramidopyrine
      five cases, antithyroid drugs four cases, non steroidal anti-inflammatories drugs
      four cases. Five patients died of infection during agrulocytosis. Sepsis was
      documented in three cases. We used hematopoietic growth factors in two cases.
      Neutrophils rose up to 0.5.10(9)/l between 2 to 14 days after the diagnosis and
      1.10(9)/l between 3 to 16 days. Time when absolute neutrophil count was less than
      0.5.10(9)/l was shorter (p = 0.008) when bone marrow was rich with maturation
      arrest but with few or no mature forms rather than reduction of granulocytic
      precursors. By comparison with a similar study made in the same institution
      between 1971 and 1981, there were fewer cases each year. Drugs involved were not
      similar: phenicols were not found, reference to noramidopyrine is less frequent.
      Now antithyroid drugs is becoming one of the most important etiologies.

PMID- 7569422
TI  - [Endometriosis of the diaphragm. Diagnostic aspects apropos of a case without
      pneumothorax].
AB  - Diaphragmatic disease is a rare manifestation of endometriosis. In the literature
      it is most often revealed by catamenial pneumothorax. We describe the case of a
      21-year old woman presenting with tight-sided phrenic neuralgia, lasting 18
      months. Signs of pelvic endometriosis appearing later on, laparoscopy showing
      thin lesions of endometriosis on the diaphragmatic undersurface. We review the
      few similar cases described earlier. They confirm that imaging studies are of
      little value, the diagnosis being made only after the discovery of pelvis
      disease. Our study of the multiple causes of phrenic neuralgia allows to
      establish criteria indicating when laparoscopy is warranted. Increasing practice
      of this test will shed light on the natural history of diaphragmatic
      endometriosis.

PMID- 7569424
TI  - [Introduction to meta-analytic methodology].
AB  - General considerations about meta-analysis and the different steps of this
      technique are successively discussed: definition of the main objective,
      identification of the outcome, description of the retrieval and selection of
      trials, description of the statistical analysis and interpretation of the
      results. Advantages and drawbacks of the meta-analytical technique are then
      described: 1) scientific approach, possible quantification of the therapeutic
      effect, increase of the power of a future clinical trial, synthesis of
      contradicting results, assessment of the homogeneity, subgroup analysis, analysis
      of sensibility, scientific collaboration, help for therapeutic information. 2)
      retrospective approach, inconsistency among trials, potential biases, persistence
      of some unsolved methodological problems, difficulties for a critical reading and
      for the interpretation of conclusions. In addition, some examples of published
      meta-analyses are given to illustrate the advantages and limits mentioned above.

PMID- 7569421
TI  - [Kaposi disease, limited to the skin, in ulcerated hemorrhagic rectocolitis].
AB  - We report the first case of limited cutaneous Kaposi's sarcoma during ulcerative
      colitis, in a HIV-negative 68 year-old man without any risk factors for this
      tumor. In our case, the steroid-therapy necessitated by the colitis is the most
      important aetiological factor of the sarcoma and its withdrawal leads to a
      complete remission of the tumor. The link between steroid-therapy and Kaposi's
      sarcoma is well known. A link between ulcerative colitis and Kaposi's sarcoma can
      be discussed but not proven. The possible occurrence of this cutaneous tumor
      during ulcerative colitis is of interest.

PMID- 7569423
TI  - [Spinal cord compression in bone fluorosis. Apropos of 4 cases].
AB  - The authors report four cases of spinal cord compression (three at cervical level
      and one at dorsal level) due to vertebral osteosclerosis secondary to chronic
      fluoride intoxication. Roentgenograms showed typical diffuse densification of
      vertebral bodies, calcifications of bony insertions of many ligaments, discs and
      interosseous membranes. Urinary fluoride was markedly increased in two cases. In
      the other two cases the bone biopsy was suggestive of skeletal fluorosis. Spinal
      computed tomography showed severe cord compression due to posterior osteophytes.
      Good improvement was observed after surgical decompression in one case. Fluorosis
      was described as a consequence of endemic exposure to high fluoride content in
      soil and natural ground water in North Africa. Fluorotic myelopathy was due to
      bone excrescences mainly affecting the spine.

PMID- 7569426
TI  - [A pea-shaped bone!].

PMID- 7569425
TI  - [Multidrug-resistant tuberculosis. Epidemiology, treatment, prevention and
      diagnostic research].
AB  - The recent augmentation of the prevalence of multidrug resistant (MDR)
      tuberculosis is related to the high incidence of tuberculosis in HIV infected
      people, especially in those with low social status and no medical care; several
      nosocomial epidemics of MDR tuberculosis were observed in American and European
      institutions where HIV-infected persons were hospitalized; these MDR tuberculosis
      were associated with a high mortality-rate and frequent nosocomial transmission
      to immunocompromised contacts and care workers. The rapid institution of an
      adequate treatment with ancient antituberculosis agents (cycloserin, capreomycin,
      aminoglycosides) and/or new drugs (rifabutine, ofloxacin, sparfloxacin, etc) is
      necessary to avoid mortality and to diminish transmission. Prevention of MDR
      tuberculosis transmission is very important: patient isolation, adequate and
      prolonged therapy, better detection of resistance with gene-amplification methods
      (PCR) which are under investigation.

PMID- 7569427
TI  - [Dendritic cells].

PMID- 7569429
TI  - [Cloning of the ob gene, a decisive advance in genetics of obesity in the mouse
      and in man].

PMID- 7569428
TI  - [Multiple cerebral tuberculoma. Apropos of a case].

PMID- 7569431
TI  - [Congestive heart failure in the elderly. Value of Doppler echocardiography].
AB  - Fifty-eight consecutive elderly patients (seven men and 51 women, mean age 84 +/-
      6) admitted for congestive heart failure were prospectively investigated by
      doppler echocardiography in order to 1) define the prevalence of cardiac failure
      with normal left ventricular systolic function, 2) estimate the role of
      abnormalities of left ventricular filling (diastolic dysfunction), 3) evaluate
      echodoppler parameters for assessment of diastolic function: ratio of early peak
      on atrial peak of filling velocities (E/A), mitral deceleration time (MDT) and
      isovolumic relaxation time (IRT). Of the 58 patients, 32 (55%) had normal left
      ventricular systolic function and 26 (45%) had systolic dysfunction. Of the 32
      patients with normal systolic function, diastolic function could not be evaluated
      in nine patients, was abnormal in 16 and normal in seven. Congestive heart
      failure with normal systolic function is very frequent in the elderly subject.
      Sensitivity of clinical data being too low, doppler echocardiography is the
      easiest noninvasive technique for defining abnormalities of both left ventricular
      systolic and diastolic function. In the elderly, MDT and IRT are more sensitive
      parameters than E/A for the diagnosis of diastolic dysfunction.

PMID- 7569430
TI  - [Goodpasture syndrome: role of an epidemiological factor? Apropos of two cases].
AB  - Goodpasture's syndrome is a rare pneumorenal syndrome. Although the antigenic
      target of this auto-immune disorder is now known, its etiology remains debated.
      We report two cases of Goodpasture's syndrome occurring in similar epidemiologic
      conditions concerning the moment the disease began, the age and sex of the
      patients, their place of residence and work and manipulation of chemicals. Thus,
      a common environmental factor could have been the trigger event of the
      Goodpasture's syndrome. The epidemiologic features of this disease are reviewed.

PMID- 7569433
TI  - [Treatment of intermediate-grade non-Hodgkin lymphoma in adults].
AB  - In the past 20 years increasing incidence 15/100,000 of non Hodgkin's lymphoma
      (NHL) has been observed. Despite their heterogeneity, intermediate grade NHL are
      potentially cured with chemotherapy. Advances in our understanding of the biology
      and in their treatment have been made. Factors, such as age, stage, performance
      status, and predicting treatment outcome are useful parameters to decide on the
      intensity of chemotherapy. With conventional treatment, 80% of the patients
      without adverse prognostic factors can be cured. For patients with at least two
      adverse factors only 40% are long term survivors. Different dose-escalation
      chemotherapy regimens have been tested including autologous hematopoietic stem
      cell transplantation (ASCT). At the present time, no clear improvement has been
      seen in randomized trial when intensification is made after obtention of complete
      remission. However, for relapsing patients ASCT can provide 46% disease free
      survival in patients still sensitive to salvage chemotherapy and ASCT is the
      therapy of choice under 60 years old. New development of technology with
      mobilized peripheral stem cell (PBPC) allowed to develop early intensive
      treatment with acceptable toxicity. Encouraging results have been reported and
      tested in randomized trial in patients less than 60 years old. Improvement of the
      treatment of older patients remains problematic considering that chemotherapy can
      increase hematopoietic and non hematopoietic lethal complications reducing the
      chance to achieve complete remission.

PMID- 7569432
TI  - [Proarrhythmic effects of anti-arrhythmia agents].
AB  - Antiarrhythmic medications are widely used either at the ventricular or
      supraventricular level. However, those drugs can induce severe side effects.
      Actually, antiarrhythmic drugs are paradoxically able to favour the occurrence of
      new arrhythmias or aggravate the preexisting arrhythmia for which they were
      indicated. These proarrhythmic effects have been found in 10 to 20% of patients,
      as evidenced by literature. Moreover, the CAST study showed a significant
      increase in mortality in patients with non sustained ventricular arrhythmias
      after myocardial infarction who were treated with either flecainide or encainide,
      compared to the placebo group. This overmortality seems to be due, in large, to
      the proarrhythmic effects of antiarrhythmic drugs. Several mechanisms have been
      evoked, related to the type of antiarrhythmic drug and to the presenting
      arrhythmia: early post-depolarization due to slow calcium and sodium inward
      currents in the case of torsades de pointes, facilitation of intraventricular
      reentries in the case of class 1c antiarrhythmic drugs, facilitation of the
      ventricular response of atrial arrhythmias. These deleterious effects, that can
      be very serious, are unpredictable, not toxicity-related and all antiarrhythmic
      drugs are involved. Their detection appears to be difficult and is based upon
      ECG, Holter monitoring, treadmill test and possibly electrophysiologic study. The
      use of antiarrhythmic drugs requires the knowledge of their proarrhythmic
      effects, the analysis of the benefit-risk ratio--particularly if left ventricular
      function is impaired--and careful monitoring.

PMID- 7569434
TI  - [Late manifestation of congenital intrahepatic portacaval shunt in a healthy
      liver].
AB  - We report the discovery of a congenital intrahepatic portocaval shunt during
      heart failure in a 68 year-old woman, without cirrhosis or portal hypertension.
      She had hepatic encephalopathy. Only 17 such cases have been reported. Their
      physiopathology remains unclear. Reasons for late revelation are debated. Color
      doppler imaging is very useful for diagnosis following and treatment of these
      shunts. Therapeutic options are presented.

PMID- 7569437
TI  - [Temporal lobectomy: indications and role in the surgery of epilepsy].
AB  - When a focal epilepsy proves refractory to medical therapy, surgical treatment is
      increasingly used. Most interventions consist in cortical resections, and by far
      the most common operation is a temporal lobectomy. The presurgical evaluation is
      a multi-disciplinary one, and includes history and examination,
      neuropsychological testing, neuro-imaging techniques, functional studies
      (functional imaging and intracarotid amobarbital procedure), and neurophysiologic
      data (EEG-video monitoring). When non-invasive EEG does not succeed in localizing
      the epileptogenic zone with sufficient accuracy, several invasive techniques are
      available. Each has its own advantages and disadvantages. In appropriately
      selected cases, postoperative outcome is excellent, especially in temporal lobe
      epilepsy. In general, outcome is slightly less successful in extra-temporal
      cases.

PMID- 7569436
TI  - [Transient dysfibrinogenemia and thrombocytopenia associated with recurrent acute
      pancreatitis in the course of isotretinoin therapy].
AB  - A 17 year-old young man developed two episodes of acute pancreatitis, separated
      by a 2 year interval and associated with isotretinoin therapy. In 1989, vesicular
      sludge without lithiasis was evidenced and in 1991, gall bladder stones were
      found by cholecystectomy. Concomitantly, transient dysfibrinogenemia and
      thrombopenia were present. It is interesting to note that far away from the use
      of isotretinoin, the patient suffered from another episode of acute pancreatitis
      without any coagulation disorder. The involvement of Roaccutane in cellular
      differentiation is discussed as well as its causal association with acquired
      dysfibrinogenemia and transient thrombocytopenia.

PMID- 7569439
TI  - [Spontaneous pyopneumopericardium].

PMID- 7569435
TI  - [A rare cause of paroxysmal eosinophilia: eosinophilic gastroenteritis].
AB  - The authors report the case of a 16 year-old boy admitted for the seventh acute
      occurrence in 18 months of abdominal pain associated with hypereosinophilia. Each
      episode was identical in nature and receded spontaneously after 5 or 6 days.
      Biopsy of a fiber colonoscopically obtained specimen of small intestine was
      performed. The diagnosis of eosinophilic gastroenteritis was based upon an
      infiltration of the digestive mucosa by eosinophils, the absence of elements in
      favor of other types of digestive-tract disease (parasitic, allergic,
      hematologic, or inflammatory), and the absence or other illness outside the
      digestive system. However, the incidental discovery of a distal dilation of both
      of the patients ureters during one such episode, that disappeared with the other
      symptoms, raises the possibility of a bladder location as well, and thus of a
      hypereosinophilic syndrome. Corticoids were administered then tapered down. A
      relapse occurred 2 months later. Currently, he is taking 20 mg of a corticoid
      every other day and has presented no manifestations over the last 9 months.

PMID- 7569438
TI  - [Intracerebral calcifications].

PMID- 7569440
TI  - [Medical care in Santiago, 1993].
AB  - Results of morbidity and medical care surveys performed in Santiago in 1993-94
      are presented in this paper. The study has been done in an aleatory population
      sample of 4,700 people coming from 1,000 dwellings. Main results are as
      following: The Health National Fund (FONASA) is the most important financing
      medical care's agency in Santiago (49% out of total population). A majority of
      medical services are given in private offices or clinics. Medical care systems
      show significant differences among the studied city districts. A significant
      direct correlation between people's income and private practice is noticed. One
      half of acute diseases had medical care and the other half used self care
      practices; the proportion of medical care is 29% in the case of chronic disease
      patients. National Health Service eligible people show a significant higher
      morbidity rate and medical consultation rate than other groups. Lack of medical
      care mainly depends on low severity of illness episodes or lack of symptoms in
      chronic disease conditions. In 12% out of total cases, lack of medical care was
      due to problems in the medical care systems. The quality of care was judged "good
      or excellent" by 82% of the people, "fair" by 9%, and "bad or deficient" by the
      remaining 8%. Personal expenditures due to health care are high, one third
      depending on medical care and two thirds on dental care. In the case of medical
      care the reasons for expenditures are linked to chronic diseases (60%), acute
      diseases (28%), injuries and health examinations (15%). Main activities causing
      personal disbursements are the purchase of drugs (44%), medical visits (30%),
      laboratory tests (13%) and hospital charges (7%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7569442
TI  - [Blood insulin in fasting conditions as a simple marker of insulin resistance in
      hypertensive patients].
AB  - Insulin resistance is associated to hypertension, obesity and diabetes and may be
      an independent cardiovascular risk factor. The exact assessment of insulin
      resistance requires complex metabolic studies. However, there is a good
      correlation between this parameter and fasting serum insulin levels. The aim of
      this work was to study fasting serum insulin levels by radio immuno analysis in
      43 hypertensive patients aged 56 +/- 5.5 years old (27 male, 17 obese and 8
      diabetics) and 20 normotensive controls aged 50 +/- 4.8 years old (13 male).
      Insulin levels were 3.8 UI/L in controls, 12.1 UI/L in normal weight, 15.5 UI/L
      in obese and 18.3 UI/L in diabetic hypertensives (ANOVA p < 0.001). These levels
      were above two standard deviations of control values in 50% of normal weight, 66%
      of obese and 62% of diabetic hypertensives. It is concluded that normal weight,
      obese and diabetic hypertensive subjects have high fasting insulin levels.

PMID- 7569443
TI  - [Academic performance in the 1st year and its relationship with admission
      variables in medical schools. Comparative study].
AB  - Chilean universities employ a common admission scoring system for students, based
      on high school grades, mathematic and verbal academic aptitude tests, and
      specific biology and social sciences tests. Aiming to know the predictive values
      of these tests, the standardized scores obtained in the selection tests and
      academic performance of 1094 first year medical students, admitted in 1989 and
      1990 to six universities, were analyzed. These students obtained high admission
      scores and their academic performance during the first year was low (mean grades
      ranged from 4.6 +/- 0.6 to 5.28 +/- 0.5 in different universities for a scale
      from 1 to 7). In all, except one university there was a correlation between
      admission scores and academic performance. Multiple regression analysis showed
      that admission scores explained a 13% of performance and that the parameters with
      better predictive value were high school grades, biology test and mathematics
      academic aptitude test. Verbal academic aptitude test did not have a predictive
      value.

PMID- 7569444
TI  - [Alcohol consumption and glomerulonephritis caused by IgA mesangial deposits.
      (Berger's disease)].
AB  - Alcohol ingestion is considered as a possible pathogenic agent for Berger's
      disease, since Iga mesangial deposits have been described in liver cirrhosis.
      Aiming to assess this issue, 28 patients with Berger's disease (BD) and 40
      patients with other glomerulopathies (NBD) were subjected to an enquiry about
      alcohol ingestion. Data was corroborated with 21 close relatives of BD patients
      and 34 relatives of NBD patients. No differences were observed in reported
      alcohol intake between BD patients and their relatives, however relatives of NBD
      patients underestimated their alcohol intake. No differences in alcohol intake,
      either self-reported or reported by relatives, were observed between BD and NBD
      patients. It is concluded that no differences in alcohol intake were observed
      between patients with Berger's disease and subjects with other glomerulopathies.

PMID- 7569441
TI  - [Enterohemorrhagic Escherichia coli in hemolytic uremic syndrome in Chilean
      children. Evaluation of different technics in the diagnosis of the infection].
AB  - Enterohemorrhagic Escherichia coli (EHEC), have been associated with pathogenesis
      of hemolytic uremic syndrome (HUS) worldwide. Our aim was to determine the
      association of EHEC infection and HUS in Chilean children. During may 1991 and
      october 1993, 34 children with HUS and 33 age matched controls (children with
      diarrhea that did not develop HUS) were enrolled in a case/control study. For
      each child a stool and serum sample were obtained at admission. Stools were
      processed for common enteropathogens and for EHEC identification. EHEC were
      identified in stools by gene probes for different virulence factors (EHEC plasmid
      associated fimbria, Shiga-like toxin I, Shiga-like toxin II and eae adherence
      factor) and by detection of free fecal toxin by a neutralization assay in Vero
      cells. Sera were processed for anti-cytotoxin antibodies also by an assay in Vero
      cells. Enteropathogens were isolated in 20.6% and 15.5% of HUS and control
      children respectively (p = NS). 91% of the HUS children and 73% of the control
      children were EHEC positive by one or more of the techniques used (p = 0.05). Of
      the three detection methods used for EHEC, only free fecal cytotoxin was
      significantly more common in HUS children than controls (45.5% vs 9% p = 0.007).
      Genotype patterns of HUS and controls strains were similar except for a trend
      towards a higher frequency of non-toxigenic strains in the control group.
      Serogroup O157 was more common in HUS children than in controls (9% vs 0% p =
      0.036). In Chile as in other countries, EHEC infection is common and
      significantly associated with occurrence of HUS. Infection with EHEC strain O157
      seems to be an important risk factor for HUS.

PMID- 7569445
TI  - [Acute altitude sickness and ventilatory function in subjects intermittently
      exposed to hypobaric hypoxia].
AB  - Aiming to assess the magnitude of acute mountain sickness symptoms and
      ventilatory function in subjects intermittently exposed to hypobaric hypoxia, we
      studied 48 healthy men aged 32.6 +/- 8.2 years old who worked in a gold mine at a
      altitude of 4600 m, using a schedule of 8-12 days of work at the mine followed by
      4 days of rest at the sea level. Studies were performed at the sea level (A),
      during the first two days of ascension (B) and after three or four days of stay
      at 4600 m (C). Mountain sickness symptoms were evaluated with a questionnaire
      devised in the 1991 International Hypoxia Symposium and respiratory function was
      assessed with a Collins Eagle II respirometer, following American Thoracic
      Society recommendations. Subjects reported mild to moderate symptoms during the
      first 24 hours of ascending (mean score of 6.4 +/- 3.1 for a maximum of 15).
      Forced vital capacity fell significantly in period B and returned to normal in
      period C and forced expiratory volume in 1 s did not change in any period.
      However, maximal expiratory flow and maximal midexpiratory flow rate
      significantly increased and remained elevated during the four days stay at the
      mine. No correlation was found between acute mountain sickness symptoms and
      changes in ventilatory function.

PMID- 7569446
TI  - [Dietary carotene intake and lung cancer among men from Santiago].
AB  - Aiming to assess the association between carotenes and vitamin A intake and lung
      cancer, a case control study was performed. Sixty one male subjects with lung
      cancer and 61 controls paired for age, sex and smoking habits from 6 hospitals in
      Santiago were analyzed. Based on a consumption tendency enquiry, the mean weekly
      intake of food groups, carotenes and vitamin A was calculated, considering
      seasonal variations. Results showed that cases consumed less "winter" vegetables
      than controls (chard, beet, chicory, spinach and cabbage) but no differences
      between groups in carotene and retinol consumption. It is concluded that patients
      with lung cancer have a lower consumption of carotene rich vegetables.

PMID- 7569447
TI  - [Clinical characteristics and natural history of human immunodeficiency virus
      infection. Study in a Chilean population served at a multiprofessional pilot
      center].
AB  - Four hundred and eighty six infected adults (90.7% men) were prospectively
      followed from 1988 to 1993 at a multiprofessional center in Santiago, Chile.
      87.8% of male patients (pts)--84% of them homo/bisexual--and 64.4% of women
      acquired the infection sexually. At the beginning of the follow up (F/U) 51% of
      men and 71% of women were asymptomatic and 30% of the total group had AIDS. (AIDS
      definition: CDC 1993, excluded CD4 lymphocyte count < 200 x mm3). 240/486 (49.4%)
      had developed AIDS at the end of the study (12/31/93). AIDS defining events (ADE)
      were: interstitial pneumonia (confirmed or suggestive as caused by P. carinii
      [PCP]), 25%; tuberculosis (all forms), 22.1%; wasting, 13.8%; Kaposi Sarcoma,
      9.2%; esophageal candidiasis, 6.7%; isosporiasis, 5.4%. Of all PCP cases, 72%
      were ADE, the rest, post.AIDS'. As expected, AIDS pts continued having major
      complications (mainly bacterial pneumonias, PCPs, esophagitis, tuberculosis and
      diarrhea due to I. belli and Cryptosporidium. Less frequently, but also observed,
      were toxoplasmic encephalitis and cryptococcal meningitis). Known mortality
      (excluded abandonment of F/U) was 27% for the whole group and varied from 5.8%,
      51.6% to 69.2% for the first, 4th and 6th year of F/U respectively. For II-III
      CDC pts the mortality was 5% and 57% and for IV CDC pts it was 38% and 100%
      during the first and 6th year of F/U respectively. 36%, 53%, 74% and 85% of the
      pts followed for 1, 3, 5 and 6 years respectively had developed AIDS by the end
      of 1993. Multifactorial causes with either diarrhea, wasting or both were
      responsible for the death in half the pts in whom this was known, 15% died of
      respiratory complications and 5.7% of cryptococcal meningitis. 80% of AIDS pts
      survived their ADE. This study has provided information about the clinical
      profile of the HIV infection and natural history of the disease in Chile.

PMID- 7569450
TI  - [Quadriceps myopathy: a type of late focal dystrophy in a case].
AB  - A 62 years old male with a slowly progressive focal myopathy is presented. He had
      noticed weakness in the lower limbs for three years and weakness in the upper
      limbs for one year. He had bilateral atrophy of quadriceps and biceps muscles,
      absence of knee jerks and hypertrophy of the calves. Needle EMG showed myopathic
      motor units. Hystological study was compatible with muscular dystrophy. The
      clinical and laboratory characteristics of this patient are in keeping with what
      has been described as "Quadriceps Myopathy" as a form of a muscular dystrophy.

PMID- 7569449
TI  - [Primary HIV infection. Clinical and serologic characteristics].
AB  - An acute clinical picture of variable intensity may occur during the initial
      primary phase of HIV infection, it may however pass unnoticed. We report 12
      seronegative subjects (11 male homosexuals, 1 female heterosexual, aged 18 to 44
      years old), that presented an acute clinical picture preceding seroconversion.
      All had a sudden beginning, resembling an acute mononucleosis in 10 and with an
      aseptic meningitis in two. Intensity and duration were variable, lasting a mean
      of 14 (range 5-44) days an remaining asymptomatic thereafter. Most patients
      presented a discrete leukopenia with lymphopenia at the expense of CD4
      lymphocytes, followed by an absolute lymphocytosis in some, with an increase in
      CD8 lymphocytes. All became positive for HIV; circulating HIV antigen was
      identified in three and IgM anti-HIV antibodies were detected during the
      symptomatic period by third generation ELISA in other three. It is concluded that
      the clinical picture of primary HIV infection has identifiable clinical
      serological and immunological features and its recognition has diagnostic and
      preventive implications.

PMID- 7569448
TI  - [Seroprevalence of HTLV-I in relatives of patients with spastic paraparesis
      (HAM/TSP and PEP)].
AB  - The seroprevalence of HTLV-1 was studied in parents, brothers, siblings and
      sexual partners of 147 patients with spastic paraparesis associated to HTLV-1
      (HAM/TSP) and 84 patients with HTLV-1 negative spastic paraparesis (SP).
      Seroprevalence was 29.1% for HAM/SP and 0% for SP relatives (p < 0.001); the last
      figure is similar to that of the general population. Seroprevalence in sexual
      partners was 65%, suggesting that sexual intercourse is the principal route of
      transmission. Likewise, seroprevalence in siblings of mothers with HAM/TSP or
      HTLV-1 positive was 17.6%, suggesting a high maternal transmission.

PMID- 7569451
TI  - [Hypophosphatemic osteomalacia acquired after renal transplantation: a a cause of
      severe osteoporosis].
AB  - Renal osteodystrophy improves after renal transplantation but, after the
      procedure, other forms of bone disease emerge. We report a male patient that
      received a renal allograft four years before, who consulted for low back pain
      secondary to multiple vertebral compression fractures. The patient had good renal
      function, a parathormone independent hyperphosphaturia, normal 25-OH
      cholecalciferol, increased urinary hydroxyproline, decreased osteocalcin, reduced
      bone density and a bone biopsy revealing osteomalacia. The diagnosis of
      hypophosphatemic osteomalacia was reached and treatment with phosphates and
      ergocalciferol was started but, despite this, the patient suffered a new fracture
      two years later. Two mechanisms can produce hypophosphatemia after a renal
      transplantation: a parathormone excess due to the previous renal failure, that
      disappears during the first year after the transplantation or a derangement in
      renal phosphate transport that can be due to a generalized proximal tubule solute
      transport derangement (Fanconi syndrome), parathormone hypersensitivity or to an
      "idiopathic" hyperphosphaturia. Despite a good treatment, bone mass is not
      recovered and there is a high fracture risk. Mineral metabolism must be closely
      monitored after a renal allograft and its alterations must be quickly treated.

PMID- 7569453
TI  - [Development of traditional careers at new universities. The case of medicine].
AB  - In 1981, the educational system in Chile was diversified characterizing
      Universities, Professional Institutes and Technical Training Centers. The
      provincial seats of traditional Universities were transformed in independent
      universities, which strongly increased its number. A number of private
      universities also emerged. This strategy was quantitatively successful,
      duplicating the number of youngsters between 19 and 24 years old that were
      following superior studies (from 88 to 199 per 1,000) and duplicating the
      registers at higher education institutions (from 118,000 to 244,000). The quality
      of the education is a matter of concern at the present time. In the case of
      Medicine, the Medical Schools Association has proposed to the Higher Education
      Council an accreditation system for programs that pursue the M.D. degree, based
      on explicit standards for all medical schools. Considering that teaching,
      research, laboratory and library resources in Chile are limited, accreditation is
      even more important. The splitting relationship between Medical Schools and the
      Ministry of Health, whose establishments are used as training centers, is also
      worrisome. Finally the physician:inhabitant relationship in Chile is adequate for
      its development level (1:960). Its geographical distribution, however, is highly
      unsatisfactory (1:657 in Santiago and 1:2,200 in some Regions). The
      implementation of professional and economical incentives could reverse this
      situation.

PMID- 7569452
TI  - [When, why, and how to treat atrial fibrillation].
AB  - Treatment of atrial fibrillation aims to convert it to sinus rhythm and maintain
      this rhythm after conversion, to reduce ventricular frequency when fibrillation
      is not converted and to prevent systemic embolies. Conversion to sinus rhythm is
      achieved with electrical cardioversion or with intravenous antiarrhythmic drugs
      (Lanatoside C, amiodarone or beta blockers). The most useful drugs to maintain
      sinus rhythm are amiodarone, quinidine alone or associated to verapamil, sotalol
      and propafenone. The best drug used to control cardiac frequency in a rapid
      atrial fibrillation is digitalis. However, when there is a decrease in vagal tone
      and an increase in sympathetic activity, digitalis losses its effectiveness and a
      betablocker or a calcium blocker must be added. Electrical cardioversion is the
      treatment of choice for atrial fibrillation of Wolff Parkinson White syndrome.
      When there is a rapid, symptomatic and uncontrollable atrial fibrillation,
      electrical ablation of atrio-ventricular junction and the implantation of a
      definitive pacemaker is the treatment of choice. Lately, a new procedure has been
      devised, called of the labyrinth, that can re-establish sinus rhythm, atrial
      contraction and atrio ventricular conduction. The embolic risk of atrial
      fibrillation depends on its etiology and the decision to anticoagulate must
      balance the risks and benefits of this treatment.

PMID- 7569454
TI  - [Indicators of atherosclerosis risk. Evaluation with coronary angiography in non
      diabetic men with total cholesterol levels equal to or below 240 mg/dl].
AB  - We studied 90 male non diabetic patients aged between 40 and 65 years old with a
      total cholesterol of less than 240 mg/dl and not receiving cholesterol reducing
      drugs, that were subjected to elective coronary arteriography. Weight, height,
      blood pressure and smoking habits were recorded and a fasting blood sample was
      drawn to measure total and HDL cholesterol, triglycerides, apoproteins A1 and B,
      Lipoprotein(a) and plasma cholesteryl ester transfer activity. Arteriography
      disclosed coronary lesions in 54 patients. Compared to patients without lesions,
      the former had lower HDL cholesterol (34 +/- 9.8 vs 40.2 +/- 11.6 mg/dl) and
      higher total cholesterol/HDL cholesterol and apoB/apoA1 ratios. No differences
      were found for lipoprotein(a) and plasma cholesteryl ester transfer activity.
      Univariate analysis showed that low HDL cholesterol had the best predictive
      capacity for atherosclerosis.

PMID- 7569455
TI  - [A controlled study of the effect of oral contraceptives on blood pressure].
AB  - The possible hypertensive effect of oral contraceptives is a controversial issue.
      We studied 371 women, admitted to the family planning program of a state funded
      outpatient clinic, that were followed during 12 months. These women were divided
      in four groups: Group 1 was constituted by 98 women that used intrauterine
      devices. Group 2 by 98 women taking 30 micrograms of estrogen and 300 micrograms
      of progestogen. Group 3 by 83 women taking 35 micrograms of estrogen and 500
      micrograms of progestogen and Group 4 by 92 puerperal women taking 30 micrograms
      of levonorgestrel, that after six months started to use an intrauterine device (n
      = 35) or the contraceptives of group 2 (n = 38) or group 3 (n = 19). Age, initial
      blood pressure and weight were similar in the four groups. There was no
      significant change in blood pressure after 6 or 12 months of follow up in any
      group. It is concluded that contraceptives containing estrogen concentrations up
      to 35 micrograms and progestogen concentrations between 300 and 500 micrograms do
      not induced changes in blood pressure.

PMID- 7569456
TI  - [Tyrosine-protein kinase activity in breast neoplasm. Comparison with activity
      obtained in benign diseases and in normal tissues].
AB  - Tyrosine protein kinase (TPK) activity is associated to malignant cellular
      transformation. This work compares TPK activity in 27 surgical biopsy samples of
      mammary carcinoma, 10 samples of fibroadenomas, 13 samples of fibrocystic breast
      disease and 27 samples of normal mammary tissue. TPK activity was determined in
      tissue homogenates using (Val5) angiotensin II as exogenous substrate. In samples
      of mammary carcinoma, TPK activity was 33.86 +/- 31.98 pmol P32/mg protein/30
      min. This value was significantly higher that those observed in fibrocystic
      disease (3.92 +/- 2.35), fibroadenomas (13.86 +/- 10.9) and normal tissue (3.56
      +/- 3.02).

PMID- 7569457
TI  - [Presence of Helicobacter pylori in the duodenum, antrum, and fundus in control
      subjects and patients with duodenal ulcer, gastric ulcer, gastritis, or erosive
      duodenitis. Histological analysis of 357 subjects].
AB  - The prevalence of Helicobacter pylori infection was studied in 152 subjects with
      a normal upper gastrointestinal endoscopy, 125 with duodenal ulcer, 25 with
      gastric ulcer, 46 with erosive gastritis and 9 with erosive duodenitis. Two
      biopsies from duodenum, antrum and fundus were obtained from each subject during
      endoscopy for histological diagnosis and Helicobacter pylori search. None of the
      patients with normal endoscopy and 2% of patients with duodenal ulcers had
      Helicobacter pylori in duodenal biopsies. These last patients had a significantly
      higher frequency of Helicobacter pylori in the antrum (71%) than the rest of the
      studied groups. Five percent of subjects with normal endoscopy and 5% of those
      with duodenal ulcers had Helicobacter pylori in the antrum. An active gastritis
      was demonstrated in almost all patients with Helicobacter infection. Intestinal
      metaplasia occurred almost exclusively in the absence of Helicobacter pylori
      infection.

PMID- 7569458
TI  - [Comparison of 2 treatment schemes to eradicate Helicobacter pylori].
AB  - INTRODUCTION: Anti secretory drugs, antimicrobials and bismuth salts are used
      with variable success to eradicate Helicobacter pylori. AIM: To assess the
      effectiveness and rates of reinfection of two therapeutic modalities H pylori
      infection in adult patients with duodenal ulcer or non ulcer dyspepsia. METHODS:
      During upper gastrointestinal endoscopy, 5 antral and 2 fundic biopsies were
      obtained and sent for microbiological and anatomopathological study. Patients
      infected with Helicobacter pylori were randomly assigned to receive during two
      weeks omeprazole 20 mg od plus amoxicillin 500 mg tid (group A) or bismuth
      subsalicylate 260 mg bid, metronidazole 250 mg tid and amoxicillin 500 mg tid
      (group B). A new endoscopy with antral and fundic biopsies was performed to all
      patients four weeks after discontinuing treatment and six months later to those
      in whom H pylori was eradicated. RESULTS: Eighty patients (40 in each treatment
      group) completed the treatment and follow up. H pylori was eradicated in 22
      patients of group A (55%) and 28 of group B (70%). Minor adverse effects were
      reported by 5 patients in group A (12%) and 11 in group B (27.5%). Six months
      later, reinfection was documented in 12 patients of group A and 8 of group B (54%
      and 30% of those with successful treatment respectively). Ten of twenty five
      patients with duodenal ulcer had reinfections, but there was only one ulcer
      relapse. CONCLUSIONS: These two treatment modalities have similar results.

PMID- 7569459
TI  - [Radiologic visibility of breast fibroadenomas].
AB  - From a clinical point of view, all mammary fibroadenomas are similar. However
      some of them are not visible in mammograms, phenomenon probably related to
      glandular density. Aiming to elucidate whether the lack of visibility is caused
      by the glandular density or by tumor itself, a three stage study was performed.
      In 201 cases the mammographic visibility of fibroadenomas was determined and
      correlated with patient's age, the presence of fibrocystic disease and tumor
      histological type; after surgical excision, 18 fibroadenomas were sliced into 5
      mm thick samples and X rayed to determine their visibility; finally 2 visible and
      2 non visible tumors were calcinated at 550 degrees C and their ashes subjected
      to X-ray diffraction analysis. Twenty two percent of fibroadenomas were not
      visible on mammography, this percentage was higher for intracanalicular tumors,
      in younger women and in the presence of fibrocystic disease. Sixteen percent of
      excised and sliced tumors were not visible on X rays. Also, differences were
      found in X-ray diffraction studies between visible and invisible tumors, probably
      related to NaCl and KCl tumor content.

PMID- 7569460
TI  - [Papillary muscle rupture in myocardial infarction].
AB  - We report nine patients with acute mitral regurgitation secondary to post
      infarction papillary rupture operated between 1980 and 1992. Seven cases had
      posterior papillary muscle rupture. All patients were in critical conditions with
      pulmonary edema at the moment of surgery. In eight cases, mitral valve
      replacement was performed (4 with mechanical prostheses) and in one, the valve
      was repaired with papillary muscle reimplantation. Six cases were also subjected
      to myocardial revascularization with sapheneous vein grafts. Two patients (22%)
      died during the postoperative period and 4 had postoperative complications. The
      seven survivors have been followed during 6 to 115 month. Of theses, one died six
      month after surgery due to congestive heart failure, three are in functional
      class I and the rest in functional class II. It is concluded that, although
      mitral valve replacement for papillary muscle rupture has a high operative
      mortality and morbidity, long term results are satisfactory.

PMID- 7569463
TI  - [Hepatitis C virus viremia and Herpes zoster virus infection in a patient in
      hemodialysis treated with erythropoietin].
AB  - Hepatitis C virus infection in chronic hemodialysis patients is associated with
      several unresolved problems. We report a 85 years old female patient in chronic
      hemodialysis and treated with erythropoietin, that during the course of an Herpes
      zoster, presented severe malaise, weight loss and muscle weakness. Two weeks
      later, a slight rise in serum transaminases was detected. The patient had
      negative antibodies for HIV and hepatitis C virus and negative hepatitis B
      surface antigen. A PCR test was positive for serum hepatitis C virus RNA. The
      patient's condition deteriorated and she died 7 days after admission.
      Erythropoietin administration, whose immunosuppressive effect has been reported
      previously, could have influenced the dismal outcome of this patient.

PMID- 7569462
TI  - [Treatment with cyclosporine of refractory rheumatoid arthritis].
AB  - Cyclosporine may be useful in the treatment of rheumatoid arthritis refractory to
      other immunosuppressive agents, in doses of less than 10 mg/kg/day to minimize
      its nephrotoxic potential, that is enhanced with prolonged use or concomitant
      administration of anti-inflammatory drugs. We report 15 patients aged 50 +/- 12
      years with erosive rheumatoid arthritis lasting 5 +/- 4 years and refractory to
      other immunosuppressive agents. They were studied during one year and received
      cyclosporine in initial doses of 2.5 mg/kg/day that were increased to 5
      mg/kg/day, assessing clinical response, blood pressure and serum creatinine. Nine
      patients, that received a maximal dose of 3.4 +/- 0.7 mg/kg/day during 7 +/- 4
      months, improved; a 30% increase in creatinine was observed in 3, blood pressure
      raised in six and two had hepatic toxicity. In the six patients that did not
      improve, the mean treatment lapse was 4 +/- 3 months and the maximal dose
      achieved was 2.7 mg/kg/day; creatinine increased in one and blood pressure
      increased in 4. It is concluded that although the clinical response to
      cyclosporine was good, only 4 patients completed one year of treatment, due to
      the frequent secondary effects of the drug.

PMID- 7569464
TI  - [Late splenic rupture: a risk of conservative treatment].
AB  - We report a 33 year old male admitted after a traffic accident with a painful
      abdomen and an open ankle fracture. An abdominal CAT scan showed a splenic
      laceration and free ascites. A conservative treatment was decided considering
      that the patient was hemodynamically stabilized. Seven days later, the patient
      appeared hypotense and with severe pain and was operated. During surgical
      intervention, a massive hemoperitoneum due to splenic bleeding from the spleen
      was found and a splenectomy was performed. Postoperative outcome was uneventful.
      The therapeutic approach to splenic traumatism ranges from splenectomy to medical
      treatment. The report case is an example of a complication of this later
      approach.

PMID- 7569466
TI  - [Qualified particularism and affiliative virtue: emphasis of a recent trend in
      ethics].
AB  - This paper explores the implications for medical ethics of ethic of care. It
      characterizes the ethic of care in terms of two principal commitments, to
      qualified particularism and to the challenge to the centrality of affiliative
      virtue. Both of these commitments pose a much standard work in medical ethics
      characterizing moral judgment and responses as essentially impartial, principled
      and dispassionate. A care-oriented medical ethics will, it is suggested, call on
      us to focus on those virtues needed to sustain community and enhance effective
      communication and interpersonal understanding within the practices of health
      care. It stresses healing rather than curing as the objective of medical and
      nursing care; and it emphasizes the importance of trust in clinical relationship.
      As a methodological approach, the ethic of care highlights the limitations of
      principle-based approaches in guiding moral judgment and response, asserting the
      value of institutional narratives as guides to moral practice.

PMID- 7569467
TI  - [Prevalence of smoking in a general population in Valparaiso and Vina del Mar].
AB  - The aim of this work was to study the prevalence of smoking in an urban
      population from cities with low environmental pollution. From a sampling of basic
      and high school children, 1959 subjects coming from 406 homes were selected for
      the study and answered a questionnaire about smoking. The adjusted prevalence of
      smoking among subjects older than 10 years old was 36.5% and 40.8% in subjects
      older than 15 years old. Prevalence in males was 49.4% and 35% in female. However
      among subjects between 10 and 15 years old, females had a higher prevalence of
      smoking. Most subjects smoked 1 to 9 cigarettes/day, always aspirated smoke and
      consumed all the cigarette. The prevalence of passive smokers was 65.5%. It is
      concluded that the prevalence of smoking is high, that women are starting to
      smoke earlier than men and that no effort is being made to stop this habit.

PMID- 7569465
TI  - [Delayed constitutional puberty or hypogonadotrophic hypogonadism?].
AB  - This review is focused on the diagnosis, clinical and general therapeutic
      approach of constitutional growth and puberty delay and hypogonadotrophic
      hypogonadism in males, two entities that are difficult to distinguish. Clinical
      history and physical examination must be carefully performed. Delayed puberty is
      due to constitutional growth and puberty delay in the vast majority of children.
      These must be distinguished from a small fraction of boys with hypogonadism, a
      pathological condition. A number of laboratory test allow the prediction of
      puberty onset and progression. Nevertheless, the advent of highly sensitive
      immunoassay and radiometric immunoassay systems for LH, FSH and testosterone has
      not entirely solved the problems, since their values may overlap between normal
      and pathological conditions.

PMID- 7569468
TI  - The association of the platelet count and the peripheral CD8+ cell count in
      Japanese HIV-infected hemophiliacs.
AB  - To determine the factors involved in the pathogenesis of thrombocytopenia
      frequently found in human immuno-deficiency virus (HIV) infection, we studied the
      clinical and laboratory findings of 35 Japanese HIV-infected hemophiliacs
      regarding their association with thrombocytopenia. Seventeen HIV-positive
      patients were thrombocytopenic. They had fewer CD4+ cells and were in more
      advanced stages of the disease, compared with the 18 patients without
      thrombocytopenia. We carried out the stepwise regression analysis on 32 patients
      in the early stage of HIV infection, with the platelet count as the dependent
      variable, and with the CD8+ cell count, serum cholinesterase, alanine
      aminotransferase (ALT), CD4+ cell count and white blood cell count as explanatory
      variables. The CD8+ cell count, serum cholinesterase, and ALT were entered into
      the regression model as explanatory variables of the platelet count with
      statistical significance. A positive linear correlation in these 32 patients
      between the CD8+ cell count and platelet count (r = 0.50, P < 0.01) was noted. We
      conclude that the decrease of the CD8+ cell count may play a role in the
      pathogenesis of thrombocytopenia in Japanese hemophiliacs in the early stage of
      HIV-infection.

PMID- 7569461
TI  - [Prolonged remission of female hyperandrogenism after discontinuing
      glucocorticoid therapy].
AB  - Adrenal androgen hypersecretion either produced by genetic defects or reticular
      disfunction, is reduced by exogenous glucocorticoid administration and, as with
      any suppression therapy, it should relapse when the therapy is discontinued.
      However, prolonged remissions of adrenal androgen hypersecretion after
      discontinuing glucocorticoids have been described. We report 15 patients with
      adrenal hyperandrogenism and elevated levels of dehydroepiandrosterone sulfate
      that received treatment with dexamethasone. After one month of treatment with
      dexamethasone 0.5 mg/day, dehydroepiandrosterone sulfate levels returned to
      normal and remained so during a mean of 19 months receiving dexamethasone 0.25
      mg/day. One year after discontinuing therapy, hormone levels continued within
      normal range in all patients. It is concluded that a long remission period of
      adrenal hyperandrogenism was achieves after discontinuing glucocorticoid therapy.

PMID- 7569470
TI  - Pulmonary function of different categories of chronic obstructive pulmonary
      diseases in railway workers of eastern India.
AB  - Pulmonary function tests were done on 146 established chronic obstructive
      pulmonary disease (COPD) patients and 151 normal non-smoker and smoker subjects.
      These patients were assembled from Garden Reach Railway Hospital (Calcutta), West
      Bengal, India, 79 of which suffered from chronic bronchitis, 8 from chronic
      bronchitis with mild emphysema (who were included in the chronic bronchitis
      group), 38 from emphysema and 21 from asthma. In the normal subjects 75 were non
      smokers and 76 smokers. All the subjects were in the age range of 16-60 years.
      The mean values obtained in COPD patients were compared with those of normal non
      smokers and smokers in each group and amongst the different categories of COPD
      patients. All the pulmonary function tests (PFT) were measured by the standard
      spirometric technique, and the Peak Expiratory Flow Rate (PEFR) was studied by
      Wright's Peak Flow Meter. The values were expressed in body temperature at
      ambient pressure saturated with Water Vapour Pressure (BTPS). The PFT values
      significantly deteriorated in all categories of COPD patients as compared to
      normal non-smokers and smokers, but a few parameters showed exceptions.
      Significant deterioration was observed in emphysematous patients when compared to
      other categories of COPD patients. No definite trend of reduction of pulmonary
      function test values were found according to the years of suffering from the
      disease. A product moment correlation matrix showed a highly significant positive
      correlation between FVC and FEV1, in all four groups of patients. These two
      parameters also showed a strong positive relationship with FEF25-75%, FEF200
      1200ml, FEF75-85%, MVVF and PEFR. The regression equations for some of the
      closely related variables of high correlation coefficient were calculated in COPD
      patients and presented.

PMID- 7569469
TI  - [Application of neurobehavioral tests in a manufacturing automotive parts
      factory].
AB  - Three neurobehavioral tests and a profile of mood states (POMS) test, which are
      included in the WHO neurobehavioral core test battery, were applied to 106
      workers engaged in manufacturing automotive parts, especially for the purpose of
      determining the presence or absence of a significant difference in the score
      between a group of sixty-one workers chronically exposed to organic solvents and
      a group of forty-five workers unexposed. The scores of both pursuit-aiming and
      digit-symbol substitution tests were lower (P < 0.02 and P < 0.01, respectively,
      in analysis of covariance) in the group of exposed workers than in the group of
      unexposed workers. Furthermore, in the group of exposed workers, the pursuit
      aiming and digit-symbol substitution scores showed a positive correlation (P <
      0.05 and P < 0.01, respectively) to the fatigue score in the POMS test. On the
      other hand, the score of the digit span test showed no significant difference
      between the two groups. No significant correlation was found between the urinary
      hippuric acid level and the score of each of the three neurobehavioral tests.
      Therefore, among the exposed workers, the perceptual motor function evaluated in
      pursuit-aiming and digit-symbol tests seems to be affected. The neurobehavioral
      tests administered in this study are limited in number and in function, however,
      the comparison of their scores between the exposed and unexposed workers may
      suggest the presence of adversive effects of chronic exposure to organic
      solvents.

PMID- 7569471
TI  - Hypoglycemia associated with localized fibrous mesothelioma of the pleura.
AB  - Hypoglycemia is known to be a rare consequence of non-islet cell tumors. A
      patient having severe, episodic hypoglycemia was found to have a large mass
      occupying the right hemithorax. The hypoglycemia resolved immediately after
      surgical removal of the tumor. Histologic examination of the tumor revealed
      localized fibrous mesothelioma.

PMID- 7569472
TI  - [A case of postoperative hyponatremia caused by Sheehan syndrome associated with
      lung carcinoma].
AB  - A 54-year-old woman underwent a left upper lobectomy for lung carcinoma after
      which hyponatremia developed within 5 days. Her serum concentration of ADH was
      within normal range disapproving the presence of SIADH frequently associated with
      lung carcinoma. An endocrinological examination showed panhypopituitarism. From
      her anamnesis it was seen that there was much perinatal bleeding and amenorrhea.
      She was diagnosed as suffering from Sheehan syndrome. She was treated with
      glucocorticoid and beneficial results were obtained. Her serum concentration of
      natrium returned to normal and she discharged on the 74th postoperative day. We
      present this paper because we had difficulty in determining that she had Sheehan
      syndrome, and think that a careful search for a diagnosis before operation is
      important for the management of the patient during the perioperative and
      postoperative period.

PMID- 7569473
TI  - Musculoskeletal disorders in children: a study in Dutch general practice.
AB  - OBJECTIVE: This study focuses on the occurrence of musculoskeletal disorders in
      children presented in general practice. Known epidemiological studies addressing
      musculoskeletal diseases in childhood are scarce and based on a low number of
      episodes. DESIGN AND SETTING: Prospective study of all patient contacts in
      general practice. A total number of 161 general practitioners participated,
      divided into four groups, registering during four consecutive three-month
      periods. PATIENTS: All children younger than 15 years of age who visited their GP
      during the registration period. All diagnoses and working hypotheses concerning
      musculoskeletal disorders were selected. RESULTS: The total number of children in
      the study was 64,198. Disorders of the musculoskeletal system accounted for 3,699
      (7.5%) of all 49,309 contacts and for 3,046 (7.5%) of all 40,340 episodes. Of the
      3,046 episodes registered for ICPC-chapter L (musculoskeletal), 2,562 (84%) were
      new episodes, i.e. not presented to the GP before. Fifty-four percent of all new
      episodes were acute injuries. In 22% of the new episodes the general practitioner
      made a symptom diagnosis. Differences by age and sex were found for a limited
      number of diagnosis categories. CONCLUSION: Children present disorders of the
      musculoskeletal system less often than adults; they also present different
      disorders to their general practitioners. The majority of disorders presented by
      children are acute injuries, mostly sprains and strains.

PMID- 7569474
TI  - The concept of individualized hypertension care in general practice and
      outpatient clinics. The general practitioner hypertension practice study (III).
AB  - OBJECTIVE: To examine test ordering practice among general practitioners and
      hospital medical specialists according to the concept of individualized
      hypertension care. DESIGN: Mailed hypothetical case histories, with reference
      panels to categorize tests. SETTING: Uppsala-Orebro region in mid-Sweden.
      SUBJECTS: General practitioners (N = 90) and hospital medical specialists (N =
      69) in randomly sampled primary health care centres and hospitals. MAIN OUTCOME
      MEASURES: Test ordering scores. RESULTS: 84% of invited GPs and 72% of
      specialists participated. According to reference panel standards, primary care
      physicians performed 75% of obligatory tests and specialists 88%. Superfluous
      tests constituted a larger proportion of the practice of hospital specialists (11
      28%) than GPs (2-12%) in the six cases. Summarized examination scores revealed a
      wide practice variation within and between the two physician categories,
      specialists scoring significantly higher in three cases. Standardization of
      practice was more common among specialists, and differed significantly regarding
      serum potassium test, chest X-ray and ECG. Both groups deviated from current
      guidelines by omitting metabolic parameters. CONCLUSION: There is considerable
      practice variation in individualized hypertension care, which might influence
      treatment outcome. Practice audit and continuing medical education could
      contribute to care standardization according to guidelines.

PMID- 7569475
TI  - Effect of oat bran supplemented diet on hypercholesterolaemia.
AB  - OBJECTIVE: To examine the effect of oat bran supplemented diet on serum
      cholesterol in hypercholesterolaemic males who had failed to comply with a
      conventional lipid lowering diet. DESIGN: Run-in period with a conventional lipid
      lowering diet followed by supplements of oat bran (70 g per day) for six weeks.
      Wash-out period without oat bran ended the survey. SETTING: The workplace of
      Pyhasalmi Mine, Finland. SUBJECTS: 59 volunteer male miners whose serum
      cholesterol was over 6.1 mmol/l in spite of a conventional lipid lowering diet.
      MAIN OUTCOME MEASURES: Differences between means for serum cholesterol
      concentrations at different phases of the survey. RESULTS: During the oat bran
      supplemented diet serum total cholesterol decreased by 6.2%, from 6.93 to 6.50
      mmol/l (p = 0.000) and LDL cholesterol by 9.5%, from 4.64 to 4.20 mmol/l (p =
      0.000). During the wash-out phase serum total cholesterol increased by 2.3%, to
      6.65 mmol/l (p = 0.084) and LDL cholesterol by 5.0%, to 4.41 mmol/l (p = 0.021).
      The reduction in cholesterol levels on oat bran supplement correlated positively
      with the pre-treatment values. CONCLUSIONS: Oat bran seems to offer an additional
      dietary means of coping with hypercholesterolaemia.

PMID- 7569477
TI  - Living conditions and health. A population-based study of labour migrants and
      Latin American refugees in Sweden and those who were repatriated.
AB  - OBJECTIVE: To examine whether there are differences in living conditions and self
      rated health between South European labour migrants and Latin American refugees
      and those who were repatriated to Latin America. DESIGN: Analysis of data from a
      survey (face-to-face interviews) in 1991 of 338 Latin American refugees and 60
      repatriated refugees. A random sample of 161 South European and 396 Finnish
      labour migrants from the Swedish Annual Level-of-Living Surveys 1980-1981 and
      1988-89 was analysed. A random sample of 1,159 age-, sex- and education-matched
      Swedes served as controls. SETTING: Lund, a medium-sized town in southern Sweden,
      Santiago and Montevideo, capitals of Chile and Uruguay, respectively, and Sweden.
      RESULTS: Labour migrants and refugees in particular lived in rented flats while
      Swedes lived in privately-owned one-family homes. All immigrants and in
      particular repatriated Latin Americans had low material standard and meagre
      economic resources compared with Swedes. Being a Latin American refugee, a South
      European or Finnish labour migrant were independent risk indicators of self-rated
      poor health in logistic regression (multivariate analyses). Not feeling secure in
      everyday life and poor leisure opportunities were independent risk factors for
      poor health with an estimated odds ratio of 3.13(2.09-4.45) and 1.57(1.22-2.00),
      respectively. CONCLUSIONS: This study shows a clear ethnic segregation in housing
      and other living conditions between Swedes and immigrants, where Latin American
      refugees and repatriated Latin Americans were most vulnerable. All immigrants had
      increased self-rated poor health compared with Swedes. Being an immigrant was a
      risk factor for poor health of equal importance to more traditional risk factors
      such as lifestyle factors.

PMID- 7569478
TI  - Migration and health. A study of Latin American refugees, their exile in Sweden
      and repatriation.
AB  - OBJECTIVE: To analyse and elucidate the migration process in order to identify
      psycho-social themes which might act as stressors with influence on health.
      DESIGN: Qualitative in-depth interviews with eleven strategically selected Latin
      American refugees. SETTING: Latin American refugees living in Lund, a university
      town, and those who were repatriated to Santiago, Chile. PARTICIPANTS: 11 Latin
      Americans of whom 4 were repatriated to Chile. RESULTS: The migration process was
      divided into four courses of events: cultural background and everyday life;
      organized violence; the exile; the repatriation. "Themes" such as cultural and
      working identity and high control were extracted from the dialogues as central
      buffering factors against microbiological or physicochemical disease agents
      harboured by the individual. CONCLUSIONS: During the exile the cultural barrier,
      social degradation, guilt, social passivity, and ideological alienation cause a
      changed identity and low control which increase the vulnerability to
      psychological distress and physical disease.

PMID- 7569476
TI  - Chronic obstructive pulmonary disease and self-maintaining functions in the
      elderly--a population-based study.
AB  - OBJECTIVE: To describe and analyse the problems in self-maintaining activities
      among chronic obstructive pulmonary disease (COPD) patients aged 64 years and
      over. DESIGN: A case-control study. SETTING: Health Centre in Lieto, Finland,
      1990-91. SUBJECTS: 61 men and 21 women with COPD and 183 male and 63 female sex-
      and age-matched controls. The COPD group included 8 men and 11 women who also had
      asthma. MAIN OUTCOME MEASURES: Numbers of subjects with difficulties or
      dependence in self-maintaining activities. RESULTS: The number of subjects with
      difficulty or dependence in the activities of daily living (ADL) was similar
      among the patients and the controls, but some differences between the two groups
      were seen on items of mobility and instrumental activities of daily living
      (IADL). The COPD patients had more difficulties or showed dependence in moving
      outdoors or walking at least 400 m. In addition, the male COPD patients reported
      more difficulty or dependence in doing heavy housework and the female patients in
      even doing light housework than the controls. CONCLUSION: The study indicated
      that the female COPD patients in particular have a great need for assistance in
      self-maintaining functions. This information is valuable for local primary health
      care planning.

PMID- 7569479
TI  - The Harstad injury prevention study: hospital-based injury recording used for
      outcome evaluation of community-based prevention of bicyclist and pedestrian
      injury.
AB  - OBJECTIVE: To test the feasibility of a hospital-based injury recording for
      accident analysis and outcome evaluation of bicyclist and pedestrian injury
      prevention. DESIGN: Prospective injury recording lasting 7 1/2 years, using a
      quasi-experimental design. SETTING: The population of Harstad (22,000).
      INTERVENTION: Injury data were evaluated in an injury prevention group and used
      in planning a community-based intervention. Promotion of bicyclist helmet use and
      pedestrian safe behaviour was implemented by activating public and voluntary
      organizations and media. A traffic safety pamphlet containing local traffic
      injury data was distributed. Changes were made in the physical traffic
      environment. MAIN OUTCOME MEASURES: Injury rates for bicyclists and pedestrians.
      RESULTS: In 275 bicyclists upper extremity and head injuries were predominant 70%
      were below 16 years. In 137 pedestrians lower extremity injury was most frequent
      and children below 10 years had the highest injury rates. Significant injury rate
      reductions were observed after intervention for child bicyclists and pedestrians.
      CONCLUSION: A hospital-based injury recording is feasible for bicyclists and
      pedestrian accident analysis, planning injury prevention, and outcome evaluation
      of the programme. This study indicates that a significant injury rate reduction
      in children may have been the result of the intervention.

PMID- 7569480
TI  - Menstrual disorders in women. Social economic consequences of examining women
      with menstrual disorders for cancer of the body of the uterus.
AB  - OBJECTIVE: To explore the health economic consequences of menstrual disorders in
      Denmark. DESIGN: Analysis of the total costs of menstrual disorders in women, and
      a cost effectiveness analysis of menstrual disorders in women. SETTING: The
      analysis is based on retrospective 1991 data from the Danish National Patient
      Register, and from 1991 national production figures from the Danish National
      Health Insurance responsible for the primary health care sector. Furthermore, a
      survey of the incidence of cancer in Denmark in 1988 has been used. SUBJECTS: In
      the cost analysis all women who experienced menstrual disorders in 1991 are
      included, and in the cost effectiveness analysis all women with menstrual
      disorders who were examined by dilatation and curettage in 1991 were included.
      MAIN OUTCOME MEASURES: In the cost analysis the outcome measure is the total cost
      of treating and examining women with menstrual disorders in 1991. In the cost
      effectiveness analysis the outcome measure is the cost of diagnosing one new case
      of cancer of the body of the uterus in 1991. RESULTS: Menstrual disorders caused
      a resource use in the health care sector of 150 mill. DKK in 1991, i.e.
      approximately 0.4% of the total Danish health expenditure, of which at least 33
      mill. DKK were spent on the ca. 25,000 dilatations and curettages which were
      performed in hospitals and the primary sector. Approximately 600 new cases of
      cancer of the body of the uterus were diagnosed in Denmark in 1991. The cost of
      finding one woman with cancer of the body of the uterus was on average 54,500
      DKK. The cost variation per new case of cancer of the body of the uterus among
      different age groups was relatively large. The cost was 1.3 mill DKK per new case
      if the women were less than 40 years because of a low risk of having cancer of
      the body of the uterus in this age group. The cost per case was 21,500 DKK in
      women over 50 years. CONCLUSION: This article raised the question whether too
      many women under 40 years are examined today by dilatation and curettage when the
      cost effectiveness of examining the woman is considered.

PMID- 7569481
TI  - Selection of women at high risk of breast cancer using two lifestyle markers: a
      case control study.
AB  - OBJECTIVE: To select a population of women with high risk of invasive breast
      cancer by using two markers of high risk lifestyle--age at first delivery > = 25
      and daily alcohol intake > = 7 g. DESIGN: Case control study based on a
      structural interview. SETTING: Two general practices in Copenhagen, Denmark.
      PARTICIPANTS: 30 patients with invasive breast cancer and 30 age-matched
      controls. MAIN OUTCOME MEASURE: The combined selection power of the two markers
      of high risk lifestyle. RESULTS: The combined selection power of the two markers
      was significant (P < 0.025, odds ratio 4.3, 95% CI 1.2-15.6). CONCLUSION: Using
      these markers it may be possible to select about 80% of all cases of invasive
      breast cancer in a high risk group comprising only 49% of the female population.
      This could be of importance for mammography screening; rather than unselectively
      screening all women in a given age bracket, it might be preferable selectively to
      screen only the high risk group.

PMID- 7569483
TI  - From a medical consultation to a written text. 1. Transcribing the doctor-patient
      dialogue.
AB  - OBJECTIVE: To present a method for transcribing the doctor-patient dialogue
      reflecting the interactional processes of the consultation. DESIGN: Audiotape
      recording followed by transcription of one selected consultation from a Norwegian
      general practice. Analysis of the discourse according to pragmatic and
      textlinguistic principles. MAIN OUTCOME: Doctor-patient interaction made visible
      by the transcript. CONCLUSION: From a biomedical point of view, in many GP
      consultations, very little happens apart from the doctor-patient dialogue. On the
      doctor-patient interactional level, however, very much may happen. To grasp these
      events in an appropriate way, a biomedical way of thinking must be supplied by a
      linguistic-pragmatic one.

PMID- 7569485
TI  - Effectiveness of a Finnish geriatric inpatient assessment. Two-year follow up of
      a randomized clinical trial on community-dwelling patients.
AB  - OBJECTIVE: To determine whether need for services could be reduced and functional
      status and satisfaction improved by assessing and rehabilitating aged patients on
      a geriatric inpatient ward. DESIGN: A randomized clinical trial with a two-year
      follow-up. SETTING: Geriatric unit with 8 beds in a Finnish central hospital.
      PATIENTS: 312 selected community-dwelling patients were assigned to the
      intervention group (N = 104) and the control group (N = 208). INTERVENTIONS: The
      intervention patients were individually assessed and rehabilitated in a geriatric
      ward. The control group received usual home care. MAIN OUTCOME MEASURES:
      Services, institutionalization, mortality, ADL, IADL and satisfaction. RESULTS:
      At one year, the intervention group had fewer days in health centre hospitals
      than controls (13.7 vs. 22.7), but only the intervention group had the geriatric
      inpatient stay (16.5 days). No significant differences were found for cumulative
      institutionalization or mortality over 24 months. At three months, the
      intervention group experienced a more positive change than controls in continence
      (P < 0.05), housekeeping (P < 0.05) and satisfaction (P < 0.01). CONCLUSION: The
      effectiveness of comprehensive geriatric inpatient assessment and rehabilitation
      on community-dwelling patients is mild. More targeting and more follow-up
      interventions are needed.

PMID- 7569486
TI  - Health consequences of severe life events for pregnancy.
AB  - OBJECTIVE: To investigate the relationship between severe life events and
      disorders in pregnancy. DESIGN: Cohort study of pregnant women with and without
      life events. SETTING: Three Scandinavian cities, Uppsala (Sweden), Bergen and
      Trondheim (Norway). SUBJECTS: 451 parous women (para 1 and para 2) attending
      antenatal care. 107 women did and 344 did not experience severe life events just
      prior to or during pregnancy. MAIN OUTCOME MEASURES: Pregnancy disorders,
      frequency of sick leave and admission to hospital. RESULTS: There were no
      significant differences in pregnancy disorders between pregnant women with and
      without severe life events. However, women with life events were relatively more
      on sick leave and significantly more often admitted to hospital than pregnant
      women without this kind of distress in pregnancy. CONCLUSION: Severe life events
      seem largely unrelated to the incidence of specific pregnancy disorders, but seem
      to have an adverse influence on the pregnant women's general health, as indicated
      by the use of sick leave and hospitalization.

PMID- 7569484
TI  - From a medical consultation to a written text. 2. Pragmatics and textlinguistics
      applied to medicine.
AB  - OBJECTIVE: To present linguistic and pragmatic theory applied to a consultation
      in general practice. DESIGN: Reflect upon what happens during a referred
      consultation, illustrating key pragmatic concepts. Apply these concepts to the
      medical outcome of GP consultations. IMPLICATIONS: The spoken language is the
      most important tool in general practice. Speech-act theory, pragmatics, and
      textlinguistics may help us to grasp the process of doctor-patient interaction,
      and hence some essential aspects of the dynamics of clinical work.

PMID- 7569482
TI  - The importance of tight blood glucose control in diabetes.

PMID- 7569487
TI  - Graphical models for panel studies, illustrated on data from the Framingham Heart
      Study.
AB  - Recursive graphical models allow description of the simultaneous development of
      several (discrete) characteristics such as are recorded in a panel study.
      Irreversible events (death, irreversible disease occurrence) between exams are
      naturally included. This paper reviews these models and gives a detailed
      discussion of an example consisting of 49-50 year old males from the Framingham
      Heart study. The program DIGRAM is used throughout and the present paper may also
      serve as an introduction to this software.

PMID- 7569488
TI  - Experimental quantiles of epidemiological indices in case-control studies with
      non-differential misclassification.
AB  - The formulae for some typical epidemiological indices in case-control studies
      with non-differential misclassification are expressed in terms of two groups
      (alpha, beta) and (gamma, delta) of misclassification probabilities of exposure E
      and confounder C, respectively, and the initially estimated frequencies. The
      parameters alpha and beta denote the probability that subjects exposed to E are
      classified as non-exposed and the probability that non-exposed ones will be
      classified as exposed, respectively. Similarly, delta and gamma stand for the
      probability that those who have been exposed to C will be classified as non
      exposed and the probability that non-exposed subjects are classified as exposed,
      respectively. The non-negativeness of the expressions for the 'true' frequencies
      in terms of the measured ones and the misclassification probabilities leads to
      the construction of feasibility regions for alpha, beta, gamma and delta. For a
      number of 'acceptable' 4-tuples (alpha, beta, gamma, delta), all of which lie
      inside these feasibility regions, a sequence of feasible values for an
      epidemiological index is determined, after employing a systematic procedure by
      means of a 'searching net' with increments delta alpha, delta beta, delta gamma,
      delta delta. The procedure serves to determine the characteristics of the
      (experimental) cumulative distribution function for any selected epidemiological
      index. The final stage in exploiting the structure of feasibility regions for
      alpha, beta, gamma and delta is to use the cumulative distribution function to
      calculate quantiles for the index associated with prescribed probabilities.

PMID- 7569489
TI  - Misclassification of a prognostic dichotomous variable: sample size and parameter
      estimate adjustment.
AB  - Under general conditions, Lagakos showed that for an explanatory variable
      observed with error, the asymptotic relative efficiency (ARE) when using the
      observed rather than the true values in linear models, logistic models and
      proportional hazards models for survival is the square of the correlation between
      the true and observed variables. The result is useful for sample size adjustment
      when this correlation is estimable. Often, one cannot observe correct values of
      the explanatory variable under any circumstances. We show, however, that under
      the models considered by Lagakos for a dichotomous explanatory variable, the ARE
      equals the kappa statistic in a read-reread protocol. Consequently, one need not
      know 'truth' in this situation to estimate the ARE and to adjust sample size to
      maintain desired power; divide the estimated sample size obtained with the
      assumption of no measurement error by the consistent estimate of the kappa
      statistic (which is unlikely to be zero or negative). We then develop
      heuristically an adjusted estimate of the beta parameter in a proportional
      hazards survival model. The work was motivated by analyses of the Childhood Brain
      Tumour Consortium database. Examples from this database illustrate the method.

PMID- 7569491
TI  - Risk scores from logistic regression: unbiased estimates of relative and
      attributable risk.
AB  - In epidemiology, the risk of disease in terms of a set of covariates is often
      modelled by logistic regression. The resulting linear predictor can be used to
      define the extent of risk between extremes, and to calculate an attributable risk
      for the covariates taken together. As is well known, straightforward use of the
      linear predictor, on the sample from which it was derived, to obtain estimates
      the relative and attributable risk will be biased, often seriously. Use of the
      jack-knife technique is extended to produce asymptotically unbiased estimates of
      relative and attributable risks. The asymptotic variances associated with these
      estimates are derived by using the formulae of conditional variances. They are
      applied to the results of a case-control study of stomach cancer.

PMID- 7569490
TI  - Logistic regression with incompletely observed categorical covariates-
      investigating the sensitivity against violation of the missing at random
      assumption.
AB  - Missing values in the covariates are a widespread complication in the statistical
      inference of regression models. The maximum likelihood principle requires
      specification of the distribution of the covariates, at least in part. For
      categorical covariates, log-linear models can be used. Additionally, the missing
      at random assumption is necessary, which excludes a dependence of the occurrence
      of missing values on the unobserved covariate values. This assumption is often
      highly questionable. We present a framework to specify alternative missing value
      mechanisms such that maximum likelihood estimation of the regression parameters
      under a specified alternative is possible. This allows investigation of the
      sensitivity of a single estimate against violations of the missing at random
      assumption. The possible results of a sensitivity analysis are illustrated by
      artificial examples. The practical application is demonstrated by the analysis of
      two case-control studies.

PMID- 7569492
TI  - A bivariate cumulative probit regression model for ordered categorical data.
AB  - This paper proposes a latent variable regression model for bivariate ordered
      categorical data and develops the necessary numerical procedure for parameter
      estimation. The proposed model is an extension of the standard bivariate probit
      model for dichotomous data to ordered categorical data with more than two
      categories for each margin. In addition, the proposed model allows for different
      covariates for the margins, which is characteristic of data from typical
      ophthalmological studies. It utilizes the stochastic ordering implicit in the
      data and the correlation coefficient of the bivariate normal distribution in
      expressing intra-subject dependency. Illustration of the proposed model uses data
      from the Wisconsin Epidemiologic Study of Diabetic Retinopathy for identifying
      risk factors for diabetic retinopathy among younger-onset diabetics. The proposed
      regression model also applies to other clinical or epidemiological studies that
      involve paired organs.

PMID- 7569493
TI  - Estimation of the proportion of genetic cases in late-onset diseases: an
      application to Alzheimer's disease.
AB  - In diseases with a complex etiology including a genetic component, an important
      issue is to determine the proportion of cases really having inherited the
      disease. This is not easy in late-onset diseases where censoring might obscure
      the transmission pattern of the disease and give an apparently non-genetic
      distribution of the cases. We present a model that allows the estimation of the
      proportion of genetic cases in late-onset diseases. This model takes censoring
      into account by explicit modelling of the time dependency of the onset of the
      disease. The model is illustrated with an example based on an epidemiological
      survey in Alzheimer's disease and with simulated data.

PMID- 7569494
TI  - Heterosexual transmission of HIV analysed by generalized estimating equations.
AB  - A longitudinal analysis of a partner study is compared with a cross-sectional
      analysis which identify behavioural and biological risk factors for heterosexual
      transmission of HIV. Using generalized estimating equations (GEEs) a random
      effects logistic model is used for the longitudinal analysis. These approaches
      are illustrated by the Edinburgh heterosexual partner study. The longitudinal
      analysis finds that 'high-risk' sexual practices, unprotected intercourse for HIV
      and a low CD4 count in the index case significantly increase the risk of HIV
      transmission. The cross-sectional analysis, however, only indicates 'high-risk'
      sexual practices as favourable for HIV transmission.

PMID- 7569496
TI  - A simple test for spatial pattern in regional health data.

PMID- 7569495
TI  - Robust Bayesian methods for monitoring clinical trials.
AB  - Bayesian methods for the analysis of clinical trials data have received
      increasing attention recently as they offer an approach for dealing with
      difficult problems that arise in practice. A major criticism of the Bayesian
      approach, however, has focused on the need to specify a single, often subjective,
      prior distribution for the parameters of interest. In an attempt to address this
      criticism, we describe methods for assessing the robustness of the posterior
      distribution to the specification of the prior. The robust Bayesian approach to
      data analysis replaces the prior distribution with a class of prior distributions
      and investigates how the inferences might change as the prior varies over this
      class. The purpose of this paper is to illustrate the application of robust
      Bayesian methods to the analysis of clinical trials data. Using two examples of
      clinical trials taken from the literature, we illustrate how to use these methods
      to help a data monitoring committee decide whether or not to stop a trial early.

PMID- 7569497
TI  - Analysis of pseudo-profiles in organ pharmacokinetics and toxicokinetics.
AB  - In general, the pharmacokinetic model parameters, like rate constants, area under
      the curve (AUC) etc. are estimated via a two-stage procedure, where the values
      obtained from concentration-time relationships within one subject (experimental
      unit) are considered to be functionally related to the drug concentrations
      measured. In many cases 'mean' estimators and their respective standard errors
      are calculated afterwards. The determination of drug concentrations in organs as
      well as in the serum of small animals (mice, rats) in dependence of the time
      after administration often does not permit the establishment of reasonable
      profiles within one subject suited for conventional pharmacokinetic analyses and
      tolerability studies. Frequently, only one experimental value per organ or animal
      is recorded. The consequence is that most pharmacokinetic parameters are to be
      estimated on the basis of the mean concentrations rather than via the mean of
      individual parameter estimates. In all cases of a non-linear relationship between
      a target item and the concentration, the mean-concentration based estimators and
      the two-stage profile based estimators need not coincide. In addition, in the
      former case variance estimators may be either difficult to obtain or not
      deducible. In order to get variance estimators as well as to enable comparisons
      between different treatment regimens, in addition to bioequivalence testing as a
      step towards human dose finding studies, various resampling techniques
      (parametric and non-parametric bootstrap) were applied to generate pseudo
      profiles from independent measurements and compared to their more conventional
      counterparts where applicable. Simulation studies based on different predefined
      pharmacokinetic models (first-order elimination after i.v. bolus, first-order
      elimination after first-order absorption, simple capacity-limited kinetics)
      revealed that even the non-parametric pseudo-profile stratified 'bootstrap'
      (resampling with replacement per time point) performs quite satisfactorily.

PMID- 7569498
TI  - The case for cross-over trials in phase III.
AB  - There is a common belief that cross-over trials should not be used in phase III
      of drug development. This was reinforced by a statement in the draft CPMP Note
      for Guidance on biostatistical methodology in clinical trials which was
      circulated for review in March 1993: 'Hence crossover trials in patients should
      be avoided as far as possible'. We do not share this belief. Historically, many
      successful drug developments in indications such as hypertension and asthma have
      depended heavily on cross-over trials in their phase III programmes, leading to
      regulatory approval for a number of well established medicines. The evidence on
      which these developments were based appeared sound at the time, and has not been
      questioned by later experiences with these medicines. Furthermore, the general
      level of understanding of these medical indications is now even more well
      developed, and hence the circumstances under which cross-over trials may be used
      to advantage for new drugs in phase III are even more likely to be correctly
      identified. There are some well-known disadvantages of cross-over trials relative
      to parallel group trials. These are reviewed and the ways in which early
      indications of such problems might be detected in phases I and II or elsewhere
      will be discussed. However, there are also two key advantages, the well-known one
      of study size and a less well-known one arising in the context of treatment-by
      patient interaction. In phases I and II these advantages lead routinely to the
      use of the cross-over design. Some methods of analysing cross-over trials have
      been criticized in a number of recent articles. We compare the properties of a
      number of alternative analysis strategies by means of simulation and conclude
      that these concerns about methods of analysis do not imply that cross-over trials
      should be avoided, especially if baseline measurements can be included in the
      design. Any small risks attached to their use should not normally concern the
      regulator as they will tend to diminish estimates of treatment effects rather
      than enhance them. In summary, cross-over trials remain a potentially valuable
      research tool in the development of new medicines at all stages including phase
      III. It is unnecessary and counterproductive to exclude them from use.

PMID- 7569499
TI  - Planning and revising the sample size for a trial.
AB  - The sample size for a trial depends on the type I and type II error rates and on
      the minimum relevant clinical difference, all of which are known, and on the
      anticipated, but unknown, value of a measure of variation for the key response.
      This measure is the overall response rate when the key response is binomially
      distributed, or the residual variance in each treatment group when the key
      response is continuous and normally distributed. Since the true value of the
      measure is unknown, it must be guessed or estimated from previous trials. We
      describe approaches to determine an appropriate value for it, both before the
      trial begins and after it has begun, for use in calculating the final sample
      size. These approaches differ from previously described 'internal pilot' methods
      in not requiring unblinding of the treatment assignments in the trial. They
      preserve the power and do not affect the type I error rate materially. The
      approaches can be applied to longitudinal studies where the rate of change over
      time is the response of interest, and to group sequential trials.

PMID- 7569501
TI  - Use of the repeated cross-over designs in assessing bioequivalence.
AB  - We consider applications of the repeated 2 x 2 cross-over design to evaluating
      bioequivalence between the two formulations. The repeated 2 x 2 cross-over design
      allows us not only to assess bioequivalence on average bioavailability and to
      examine the subject-by-formulation interaction but also to obtain independent
      unbiased estimates of intrasubject variability. One consequence of unequal
      intrasubject variabilities is that the sum of squares of intersubject residuals
      and the sum of squares of subject-by-formulation residuals are not independent.
      We also discuss the relative merits of this design as compared to the standard 2
      x 2 cross-over design without repeated measurements in terms of precision and
      sample size with respect to the ratio of the number of subjects to the repeated
      measurements per subject. We investigate other uses of the 2 x 2 cross-over in
      examining the bioequivalence between the two different dosing regimens. Possible
      applications of other repeated cross-over designs to bioequivalence for more than
      two formulations are explored. A numerical example illustrates the proposed
      procedure.

PMID- 7569502
TI  - Assessing sensitivity in suspension to cytosine arabinoside: statistical
      analysis, associations with clinical outcome and experimental design.
AB  - As part of the treatment protocol in 40 leukaemia patients using cytosine
      arabinoside for remission induction therapy, the sensitivity of each patient's
      blast cell progenitors to the drug was determined by the liquid suspension assay.
      To summarize the dose-response curves obtained in this assay, we considered a
      model that assumes the existence of a resistant subpopulation of progenitor
      cells. We also considered the median effect model popular in pharmacokinetics.
      Both models were similar in their ability to describe the data. Parameter values
      that characterize a low baseline number of progenitor cells exhibiting high
      sensitivity both at low and high dosages were found to indicate good prognosis.
      We also identified a simple, economical, robust and efficient design for
      conducting future assays.

PMID- 7569500
TI  - Bayesian predictive approach for inference about proportions.
AB  - This paper investigates the Bayesian procedures for comparing proportions. These
      procedures are especially suitable for accepting (or rejecting) the equivalence
      of two population proportions. Furthermore the Bayesian predictive probabilities
      provide a natural and flexible tool in monitoring trials, especially for choosing
      a sample size and for conducting interim analyses. These methods are illustrated
      with two examples where antithrombotic treatments are administrated to prevent
      further occurrences of thromboses.

PMID- 7569503
TI  - Defining, monitoring and combining safety information in clinical trials.
AB  - Assessment of clinical trial safety data for industry, regulatory agencies,
      medical practitioners and patients requires definition and measurement,
      monitoring, and overall analysis. Prospective 'safety' definitions and reliable
      measurement tools reduce inefficient data collection and improve the validity of
      resulting analyses. Statistical tools can help investigators monitor safety data
      from controlled clinical trials and help improve post-marketing surveillance.
      Also, when evaluating overall safety, one needs to assess all available
      information by combining information from many trials and other sources. Planning
      for this combined assessment, incorporating flexibility to assess unanticipated
      yet important nuances in individual trials, may be more important than the actual
      statistical analysis method used. A keen awareness of the future needs of
      consumers of this information is quite important. Some current proposals to
      combine safety information will be discussed.

PMID- 7569505
TI  - A technique for summarizing longitudinal data.

PMID- 7569504
TI  - Comparing the bivariate effects of toxicity and efficacy of treatments.
AB  - Medical studies often involve comparing the toxicity and efficacy of drugs.
      Separately evaluating toxicity and efficacy, the usual practice, does not
      correspond to how doctors manage patients and does not use the information
      provided in their bivariate relationship. This paper presents methods for
      analysing the bivariate data. One method is based on assessing the benefit for
      patient values to lie in different regions of the toxicity-efficacy plane. A
      second method includes patient thresholds for tolerating drugs. We propose
      dividing the toxicity-efficacy plane into regions where patients are likely to
      tolerate the drug. Several statistics are defined on these regions for measuring
      the toxic-therapeutic relationship, and the bootstrap is proposed for estimating
      their variances. We illustrate with treatment information available on rheumatoid
      arthritis patients.

PMID- 7569506
TI  - Statistical concepts in the planning and evaluation of drug safety from clinical
      trials in drug development: issues of international harmonization.
AB  - The assessment of the safety of new drugs during pre-marketing clinical studies
      is an important and integral part of the drug development and regulatory
      evaluation process. The International Conference on Harmonization of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a project
      that brings together the regulatory decision-makers of Europe, Japan and the
      United States of America and the experts from the pharmaceutical industry in the
      three regions to seek ways to eliminate redundant and duplicative technical
      requirements among the developed countries for registering new medicinal
      substances and products. The ICH is developing guidelines or position papers to
      achieve the goal of harmonizing technical standards in three broad areas, namely,
      drug efficacy, safety and quality. Within the area of drug safety, this paper
      will discuss three of the safety topics because of their relevant statistical
      framework, and because these topics have not, to date, received any attention by
      the statistical community. The three issues under consideration by the
      International Conference on Harmonization (ICH), are: 1. Dose-response
      information to support drug registration (especially dose/toxicity
      relationships). 2. Studies in support of special populations; Geriatrics, A Draft
      Guideline. 3. ICH Draft Guideline 3 on 'The extent of population exposure
      required to assess clinical safety for drugs intended for long-term-treatment of
      non-life-threatening conditions'. The ICH special population guideline concerning
      studies in geriatric patients is closely related to a recent Food and Drug
      Administration 'Guideline for the study and evaluation of gender differences in
      the clinical evaluation of drugs', which is another example of a 'subgroup' for
      whom specific interest exists to evaluate drug safety and efficacy.

PMID- 7569507
TI  - Choice and decisions in the development of pharmaceutical products. Proceedings
      of the 2nd International Meeting on Statistical Methods in Biopharmacy. Paris, 6
      7 September 1993.

PMID- 7569509
TI  - Dose finding strategies involving interim analyses and unbalanced treatment
      allocation.
AB  - Dose finding studies usually require the application of multiple test procedures
      (MTP). A variety of procedures is available for data analyses. Focusing on
      testing only subset hypotheses of interest requires only limited alpha
      adjustment. Specific strategies based on MTP, in particular closed test
      procedures, which also consider dropping dose groups and unequal group sizes,
      lead to substantial reduction in total sample size. Of course, strategies
      discussed here can be extended to comparisons of more than five groups, and they
      may be generalized to cover equivalence tests, too. For example, one may want to
      demonstrate therapeutical equivalence of two dose regimens like b.i.d. and o.d.
      administrations of the drug.

PMID- 7569508
TI  - Bayesian decision procedures for dose determining experiments.
AB  - This paper describes the Bayesian decision procedure and illustrates the
      methodology through an application to dose determination in early phase clinical
      trials. The situation considered is quite specific: a fixed number of patients
      are available, to be treated one at a time, with the choice of dose for any
      patient requiring knowledge of the responses of all previous patients. A
      continuous range of possible doses is available. The prior beliefs about the dose
      response relationship are of a particular form and the gain from investigation is
      measured in terms of statistical information gathered. How all of these
      specifications may be varied is discussed. A comparison with the continual
      reassessment method is made.

PMID- 7569511
TI  - Estimating the minimum therapeutically effective dose of a compound via
      regression modelling and percentile estimation.
AB  - Estimation of the minimum effective dose (MED) of a compound from a typical
      placebo-controlled dose-response study can be carried out in several ways.
      Current approaches compare treatment doses against a placebo dose via selected
      contrasts to determine the lowest dose level at which the contrast is
      statistically significant. Ruberg shows how this approach works for various
      choices of contrasts. Instead, the MTED (minimum therapeutically effective dose)
      might be defined as the lowest dose level that yields a therapeutic benefit to
      patients, on average, or to a given percentage of patients. One could use a lower
      confidence limit for the mean approach to determine the dose yielding (on
      average) a therapeutic benefit via regression modelling of the continuous
      treatment dose response. More importantly, a patient relevant approach would be
      to actually estimate regression percentiles or construct regression tolerance
      intervals. Such an approach addresses the question 'What percentage of patients
      are receiving therapeutic (yet safe) doses', instead of just knowing that a dose
      is effective 'on average', and thus would help to understand the distribution of
      patient responses at a given treatment dose. This further enables one to better
      evaluate the efficacy versus safety trade-off as dose increases and provides
      better guidelines for prescribed dose levels.

PMID- 7569512
TI  - Constructing a bootstrap confidence interval for the unknown concentration in
      radioimmunoassay.
AB  - The statistical problem associated with radioimmunoassay is known as calibration
      or inverse regression. In the current study, we propose a bootstrap procedure
      aimed at constructing an inverse confidence interval for the univariate
      calibration problem. The calibration curve is estimated either parametrically or
      by non-parametric regression. The methods are illustrated by an example.

PMID- 7569513
TI  - Inferring systemic exposure from a pharmacokinetic screen: model-free and model
      based approaches.
AB  - To infer patterns of average systemic exposure and to estimate individual
      exposures in phase III clinical trials of a new anxiolytic, two statistical
      methodologies were applied and compared: non-linear mixed-effect modelling, and a
      model-free approach based on quartiles of dose-normalized plasma concentrations
      of the drug. Although the model-based approach provides more quantitative insight
      about relationships between average exposure and demographic covariates, the
      model-free approach provides qualitatively similar results about average
      clearance and quantitatively similar results about individual exposures, and the
      model-free approach is easy and inexpensive to implement.

PMID- 7569514
TI  - An application of Bayesian population pharmacokinetic/pharmacodynamic models to
      dose recommendation.
AB  - Population pharmacokinetic data consists of dose histories, individual covariates
      and measured drug concentrations with associated sampling times. Population
      pharmacodynamic data consist of dose histories, covariates and some response
      measure. Population analyses, whether they be pharmacokinetic or pharmacodynamic
      attempt to explain the variability observed in the recorded measurements and are
      increasingly being seen as an important aid in drug development. In this paper a
      general Bayesian population pharmacokinetic/pharmacodynamic model is described
      and an analysis of data for the drug recombinant hirudin is presented. The model
      we use allows for both outliers and censoring in the concentration data and
      outlying individual pharmacokinetic parameters. We attempt to address directly
      important questions such as recommended dose size using predictive distributions
      for response.

PMID- 7569516
TI  - Scientific journals and quality of care.

PMID- 7569515
TI  - Influence of confounding factors on designs for dose-effect relationship
      estimates.
AB  - Three types of designs can be used to estimate the drug dose-effect relationship
      during phase II clinical trials: parallel-dose designs (parallel); cross-over
      designs (X), and dose-escalation designs ([symbol: see text]). Despite the use of
      non-linear mixed effect models, the potential influence of confounding factors on
      [symbol: see text] designs has not been previously fully elucidated; we undertook
      simulations to investigate this for all three experimental designs. We found
      that: (i) monotonic spontaneous evolution of the effect (EV) did not affect the
      maximum effect estimation (Emax) and the dose giving 50 per cent of this (ED50);
      (ii) EV similar to a regression to the mean gave rise to biases for [symbol: see
      text] designs; (iii) the introduction of a pharmacodynamic carry-over generates
      important biases and imprecision for [symbol: see text] designs, even when the
      carry-over is adjusted for; (iv) the introduction of non-responders resulted in
      bias and imprecision for both Emax and ED50 in all three designs.

PMID- 7569517
TI  - Moral sensitivity in nursing practice.
AB  - This study reports results of an inquiry into ethical decision making in nursing,
      focusing on moral sensitivity. The Moral Sensitivity Questionnaire (MSQ), an
      instrument constructed to measure moral sensitivity in nursing practice was used.
      The main dimensions of this questionnaire are; interpersonal orientation,
      structuring moral meaning, benevolence, modifying autonomy, experiencing moral
      conflict, and trust in medical knowledge and principles of care. The
      questionnaires were distributed to a total of 419 nurses and completed by 145
      nurses employed in psychiatric settings and 150 nurses employed in medical
      surgical nursing areas. The results show significant differences in the two
      groups and differences concerning age, length of experience and previous
      education as mental health care workers.

PMID- 7569518
TI  - The nurse in clinical practice--a qualitative analysis of nursing competence.
AB  - Swedish colleges and universities are now adapting their syllabuses to the new
      open European labour market. In this respect the syllabus for training of nurses
      is to be reorganized. Thinking in terms of health will be very important in the
      training program and will require practical experience of nursing. The aim of
      this study was to examine the demands made on competent nurses working in
      clinical practice. An open question was asked and the results were analysed by
      the constant comparative method. The 23 nurses interviewed had to answer the
      question: "What do you require of a competent nurse?" From the empirical data,
      characteristics of six different ideal types were described. A competent nurse
      has the ability--to create a good atmosphere; concentrate on the patient and
      always to have an ethical and humanitarian approach; to teach and instruct; to
      organize, make priorities, cooperate and make documentations; to use her
      theoretical knowledge and be able to put it to use; to be keen on development and
      change. The study showed that a competent nurse has a wide field of knowledge,
      but also highlighted the complex of the nursing profession. If the nursing
      student can acquire these skills she will be well prepared for her central role
      in clinical practice.

PMID- 7569519
TI  - Support of the experience of health in lucid elderly nursing home patients-
      registered nurses' perceptions.
AB  - As peace of mind has been reported by elderly nursing home patients to be an
      important aspect of health, registered nurses were asked how they could support
      the attainment of this state of mind in elderly, lucid patients. Four aspects of
      nursing support were found: support through instrumental activities, through
      daily coexistence, through genuine encounters and through empowering supportive
      interventions. Included in professional nursing was not only the responsibility
      for all nursing performed in the ward, but also the empowering support, health
      education (support to acquire a realistic picture of the situation) and support
      in dealing with situations at hand. It was concluded that these functions in
      nursing home care needed further attention and research.

PMID- 7569520
TI  - Predictors of patient-perceived quality.
AB  - Larrabee's model of quality proposes a relationship between quality and value.
      This study tested the relationship by identifying predictors of patient-perceived
      quality for nursing care. Data were obtained from interviews and records of 199
      adult patients. Candidate predictors of patient-perceived quality included
      patient goal achievement, nurse-perceived quality, and nurse goal achievement.
      Candidate predictors also included seven demographic, seven financial, six
      illness, and six hospital variables. Predictors of both patient-perceived quality
      global and patient-perceived quality total were pain severity on exit interview,
      clinic referral, unit, and patient goal achievement. Medicare nonrecipient was a
      predictor of patient-perceived quality global. Worry score on admission was a
      predictor of patient-perceived quality total. The results support the
      relationship between quality and value and between quality and beneficence
      postulated by Larrabee's model of quality. Additional investigation of these
      relationships in other populations and using other operationalizations of the
      model concepts is needed to provide further support for the model. This model is
      potentially useful for investigating quality in diverse cultures because the
      operationalization of the model concepts can be designed to reflect local,
      regional, or national values.

PMID- 7569521
TI  - The use of the Modified Norton Scale in nursing-home patients.
AB  - Patients in three nursing-home wards in Sweden were in 1991 assessed by the
      Modified Norton Scale (MNS). Of the 71 patients, 38 (49%) were considered to be
      at risk of developing pressure sores. Six of the patients had a total of eight
      pressure sores. Five sores were assessed as stage II, two sores as stage III and
      one sore as stage IV. Only two of the six patients with pressure sores had any
      preventive equipment in their beds. The nursing and medical documentation of the
      existing pressure sores was not satisfactory. Individual programs for skin care
      and routine assessment with a pressure sore prediction instrument, such as the
      MNS, would serve the dual purpose of directing the relevant measures to the
      patient groups at the greatest risk and would aid in assessing the efficacy of
      pressure sore treatment strategies.

PMID- 7569510
TI  - An extension of the continual reassessment methods using a preliminary up-and
      down design in a dose finding study in cancer patients, in order to investigate a
      greater range of doses.
AB  - In a phase I clinical trial in cancer patients, the drug involved had one known
      main adverse effect, which also occurs spontaneously in cancer patients with a
      fairly high frequency. Experiments in rats have shown marked effects of the drug
      on tumour growth in high doses, but also dose-dependent toxicity. Consequently,
      the aim of the study was to determine a dose with a prespecified, acceptable rate
      of toxicity. As a traditional design could result in inaccurate conclusions, use
      of the continual reassessment method (CRM) was considered. Twelve dose levels
      were chosen, allocating to the first patient the lowest, but safe, dose. It is
      likely that the target dose is far above that, and that CRM then would escalate
      too fast, skipping certain levels. To ensure that all dose levels inferior to the
      target dose were tried, some combined methods were proposed: (1) an extension of
      the design, combining the CRM with a preliminary up-and-down design in order to
      reach the neighbourhood of the target dose during a successive escalation, and
      (2) a restriction on the CRM of never escalate more than a single dose level.
      Simulations showed the extended CRM to be superior by making it possible to
      investigate a greater range of doses using fewer patients, and to provide more
      accurate estimates.

PMID- 7569522
TI  - From fun and excitement to joy and trouble--an explorative study of three Danish
      fathers' experiences around birth.
AB  - The role of the father has undergone considerable change in the West. Fathers of
      today are expected to take a more active part in birth preparation, birth and
      childcare than their predecessors were. The purpose of the present study is to
      describe some Danish fathers' experiences around birth. Three first-time fathers
      were interviewed at three different times: in the last month of pregnancy, two
      weeks after the birth of their child, and again three months later. Data were
      analyzed in several steps using a hermeneutical approach. The fathers'
      experiences were identified as fun and excitement at the end of the pregnancy,
      love at first sight at the birth, at which they all attended and took an active
      part, awakening when the new family was united at home and when they came to
      realize how much effort is needed in caring for an infant, and joy and trouble
      three months later. It is suggested that health personnel might benefit from the
      study in both a direct and indirect way.

PMID- 7569523
TI  - Beds used at a university hospital--a study of functions, problems and
      requirements.
AB  - The comfort and functional features of hospital beds are of fundamental
      importance to both the patients and staff on the ward. This study investigates
      the types and functions of the beds used at a large university hospital in
      Sweden, how the head nurses experienced and valued the hospital beds in their
      wards, and whether the nurses were familiar with standards, regulations and
      purchasing routines. An inventory of all the beds for adult patients was carried
      out in all 55 somatic wards. Interviews were conducted with 49 head nurses, and,
      for comparison purposes, with one purchaser as well as one expert nurse at the
      Gothenburg Medical Service Administration. The inventory reveals that the
      different wards have very similar kinds of beds regardless of specialty or caring
      needs. The head nurses stated that the beds were seldom ideal and that they
      themselves have little influence when new purchases are made. It is concluded
      that the head nurses have a considerable knowledge of the functions of hospital
      beds, which ought to be put forward in stronger terms and which should also be
      taken into account when new beds are purchased and designed.

PMID- 7569525
TI  - [What is your diagnosis? Compression-type fatigue fracture of the tibia].

PMID- 7569524
TI  - Qualitative methodology as caring science methodology.
AB  - Interest in the use of qualitative methodology is increasing among researchers
      within the field of caring sciences. Several reasons might account for this
      growing interest: disappointment from experiences with quantitative methodology
      in this field; interest in caring issues which do not lend themselves to
      quantitative analysis; and, simply, an emerging appreciation of qualitative
      methodology. There is a need for additional clarity about the applications of
      qualitative methodology in explication of caring. The major questions concern the
      suitability of qualitative methodology to the study of caring and the scientific
      status of qualitative methodology. This paper advocates qualitative methodology
      as a methodology of choice for scientific exploration in the field of caring.

PMID- 7569526
TI  - [Training counseling in general practice].
AB  - The general practitioner is increasingly confronted with questions of sports
      medicine due to the increasing importance of exercise and sport in our society.
      This article gives a short summary of important knowledge concerning the
      components of physical activity, the possibilities for testing and training and
      the planning of training. Some simple ways of exercise counselling for patients
      are shown. According to its importance, most emphasis is put on the discussion of
      endurance capacity.

PMID- 7569527
TI  - [Athletic injuries].
AB  - The increase in leisure-sports has not only brought an escalation in the number
      of sports-related injuries presenting to orthopaedists, but has also aroused
      interest for diagnosis and treatment of these injuries in sports-oriented and 
      interested physicians. The primary treatment in the sports arena remains simple:
      rest, ice, compression, elevation. The introduction of innovative imaging
      techniques beside conventional clinical and radiological examinations has
      facilitated differentiated diagnosis and has led to changes in the treatment of
      sports-related injuries. While a conservative approach has become established for
      the treatment of isolated injuries to the collateral ligaments in the knee,
      ligament ruptures of the ankle and also for certain injuries of the
      acromioclavicular joint, the complex tears of ligaments in the knee as well as
      ruptures of the Achilles tendon remain a domain of surgical treatment. Diagnostic
      and operative arthroscopy has replaced open surgery in the treatment of knee and
      shoulder trauma to hasten the restitution of proprioception, muscle power and
      rehabilitation especially in athletes. Some points relevant to the occurrence of
      sports accidents should be observed for the prevention of these injuries.

PMID- 7569528
TI  - [Heart patient and sports].
AB  - Patients with heart disease may benefit from scheduled exercising in different
      ways. Exercise tolerance is increased, risk factors are controlled, and even
      progression and regression of coronary artery disease can be influenced by
      training and diet. Psychological effects include lessened depression and reduced
      anxiety. Overall, regular physical activity is important for maintenance of
      health and may lead to a better quality of life. In order to minimize the risk of
      training, the patients should be provided with guidelines for exercising by the
      physician. Activities should include dynamic endurance exercises and properly
      selected calisthenics (without a need for high technical skills). Circuit weight
      training of moderate intensity is helpful for promoting muscle strength. Training
      has to be followed not less than 2 to 3 hours per week in at least three sessions
      at an intensity corresponding to 60 to 85% of the maximum heart rate achieved in
      a symptom-limited maximum exercise-test. Cardiac patients at high risk (decreased
      left ventricular function, persisting ischaemia, low exercise capacity, severe
      symptoms, older age) should exercise at lower intensities.

PMID- 7569534
TI  - [What is mental health?].

PMID- 7569530
TI  - [A case from practice (330). 1. HIV infection stage CDC A2. 2. Anticardiolipin
      syndrome].

PMID- 7569535
TI  - [Palliative care: various theological implications in reference to the article by
      E. Rivier, L. Barrelet and P. Beck].

PMID- 7569533
TI  - [Rhinoplasty and rejuvenation].

PMID- 7569529
TI  - [Sports and diabetes].
AB  - Diabetes and sports are not incompatible. Type-1 diabetic persons must learn how
      to adapt their insulin dosage and carbohydrate intake, in order to avoid
      hypoglycaemic attacks. In type-2 diabetic persons, an exercise program can
      contribute to decrease the cardiovascular risk and improve glycaemic control. A
      thorough check-up, oriented towards specific complications and exclusion of
      coronary heart disease, is imperative in any diabetic persons involved in an
      exercise program. Patient associations provide useful informations and offer
      programs where the patient can learn how to cope with his disease when
      exercising.

PMID- 7569531
TI  - [Childbirth in water: myth or reality?].

PMID- 7569532
TI  - [Pediatric medical emergencies in a regional hospital: appropriate locale?].

PMID- 7569536
TI  - [The immature kidney].
AB  - In humans, urine formation starts with the metanephros at the 10th week of
      gestation. Nephrogenesis progresses during gestation and is achieved around the
      35th week. Clamping of the cord is the signal for a striking increase in renal
      function which reaches mature levels at the end of the first year of life. The
      integrity of several hormonal systems (the renin-angiotensin system, the
      prostaglandins) is mandatory for kidney growth and the development of renal
      function. The mechanisms underlying renal homeostasis are fragile and can easily
      be disturbed during respiratory and cardiovascular distress, or be affected by
      the administration of vasoactive agents. Thus, perinatal asphyxia or hypoxemia,
      as seen in respiratory distress syndrome or neonatal pulmonary hypertension
      induces intense renal vasoconstriction, with consequent oligoanuria. Congestive
      heart failure also results in renal hypoperfusion and sodium retention.
      Vasoactive agents and diuretics (indomethacin, tolazoline, furosemide) used to
      threat these conditions can result in renal vasoconstriction, renal hypoperfusion
      and failure. The pathogenesis and pathophysiology of neonatal renal disturbances
      being now better defined, a rational approach to the treatment of renal
      functional abnormalities during the neonatal period is possible.

PMID- 7569537
TI  - [Kidney and water-electrolyte balance in the premature infant].

PMID- 7569538
TI  - [Diuretics in the neonatal period].
AB  - Careful management of fluid and electrolytes may require the rational use of
      diuretic agents in some neonatal pathological conditions. High efficacy diuretics
      include "loop" diuretics--furosemide, bumetanide and ethacrynic acid. The
      elimination half-life and renal effects of furosemide are prolonged in newborn
      infants as compared with adults. In congestive heart failure, the mean net losses
      associated with a 1 mg i.v. dose of furosemide, are 28 ml/kg, 3.6 mmol/kg and 0.3
      mmol/kg respectively for water, sodium and potassium. The furosemide--dopamine (2
      micrograms/kg/min) combination may improve renal insufficiency in the course of
      respiratory distress syndrome (RDS). Furosemide also decreases the deleterious
      renal effects of indomethacin. Beneficial effect of furosemide has not been
      clearly demonstrated in RDS and bronchopulmonary dysplasia (BPD). Metabolic
      alkalosis, hypokalemia, renal calcifications, cholelithiasis and worsening in BPD
      outcome have been related to long-term administrations of furosemide. The risk of
      furosemide induced-ototoxicity has not been clearly assessed in newborn infants.
      Medium efficacy diuretics (thiazides) act primarily in the early distal tubule.
      Chlorothiazide may reduce calcium urinary excretion in neonates receiving long
      term furosemide therapy. Weak diuretics (potassium-sparing diuretics and carbonic
      anhydrase inhibitors) cause excretion of less than 5% of the filtered sodium.
      Potassium-sparing diuretics are usually reserved for neonates with congestive
      heart failure and are always used in combination.

PMID- 7569540
TI  - [Should all primary care physicians be educated in ultrasonography? Survey among
      practitioners. Group of Practitioners of the University Medical Polyclinic].

PMID- 7569541
TI  - [Preventive medicine in the practitioner's office: necessary education].

PMID- 7569542
TI  - [Rheumatology: hopes and disappointments].

PMID- 7569539
TI  - [Unusual cervical and thoracic pain in 2 young patients].

PMID- 7569543
TI  - [The adolescent and secondary amenorrhea].

PMID- 7569544
TI  - [Injurious effects of geriatric hospitalization].

PMID- 7569545
TI  - [Inactivated antihepatitis A vaccine].

PMID- 7569546
TI  - [Quality of life: concept and definition].

PMID- 7569547
TI  - [The human genome project and its applications].

PMID- 7569548
TI  - [Upper digestive hemorrhage in a patient with von Recklinghausen
      neurofibromatosis].
AB  - Neurofibromatosis (Von Recklinghausen's disease) is uninherited as an autosomal
      dominant trait. It is characterised by the development of tumors in diverse
      sites, which may be benign or malignant. The case of a 39 year old woman with Von
      Recklinghausen's disease is discussed. She presented with a 3 year history of
      episodes of melaena and iron deficient anaemia. Mesenteric angiography
      demonstrated a hypervascular tumour in the jejunum. It was surgically excised
      with an anatomopathological diagnosis of neurofibroma.

PMID- 7569549
TI  - [Second tumors in pediatric oncologic patients. Report of 5 cases].
AB  - The dramatic progress observed in the survival of children treated for cancer in
      the last two decades due to the use of aggressive chemotherapy and radiotherapy
      has brought an increased incidence of second malignant tumors. Five clinical
      cases of second malignant neoplasms after a period of six months to seventeen
      years after diagnosis are presented. The second tumors observed were: one patient
      with malignant fibrous histiocytoma of the orbit after treatment bilateral
      retinoblastoma; one patient with multifocal osteosarcoma after cerebelli medullo
      blastoma; one patient with Ewing's sarcoma of the fibula after neuroblastoma of
      the adrenal gland; one case of carcinoma of the thyroid gland after osteosarcoma
      of the femur and one patient with acute lymphoblastic leukemia after been treated
      of osteosarcoma of the femur. The genetic, immunologic and therapeutic risk
      factors are reviewed and analyzed.

PMID- 7569551
TI  - [Thyroid disease among women in reproductive and non-reproductive age].

PMID- 7569550
TI  - [Clinical use of naltrexone].
AB  - The author outlines a brief review of the clinical use of the opioid antagonist
      naltrexone in the psychosocial rehabilitation of opiate addicts. The major issues
      that an ideal program with naltrexone should deal with are pointed out. Patient
      selection is analyzed with an explicit reference to their hepatic status. The
      author addresses the different stages of induction and stabilization-maintenance.

PMID- 7569552
TI  - [Pneumococcus resistance. Reconsiderations on its empirical treatment].

PMID- 7569553
TI  - [Tacrolimus (FK 506): an immunosuppression alternative in solid organ
      transplantation. (Part 2)].

PMID- 7569554
TI  - Photodynamic therapy: Part II.

PMID- 7569555
TI  - Photodynamic therapy of brain tumors.
AB  - Photodynamic therapy (PDT) is a binary treatment modality suitable for various
      malignant tumors including brain. It involves the selective uptake of a
      photosensitizer into tumor followed by intraoperative irradiation of the tumor
      with light of an appropriate wavelength to cause activation of the sensitizer and
      subsequent selective tumor destruction. PDT has been extensively investigated in
      laboratory studies and has been used in clinical trials to treat a variety of
      brain tumors, particularly gliomas. The main advantage of PDT lies in its ability
      to select out infiltrating tumor cells that are responsible for local tumor
      recurrence. The therapy has been shown to be safe clinically but adequate trials
      have yet to be undertaken to prove its efficacy and much work remains to be done
      to optimize treatment. The biological basis, laboratory studies, and clinical
      trials involving PDT in the treatment of cerebral tumors are discussed.

PMID- 7569556
TI  - Photodynamic therapy for recurrent supratentorial gliomas.
AB  - We have used photodynamic therapy (PDT) in the treatment of 56 patients with
      recurrent supratentorial gliomas who had failed radiation therapy and who were
      candidates for palliative reoperation. There were 34 males and 22 females; their
      mean age was 41 years and the mean Karnofsky score was 79. Thirty-two patients
      had glioblastoma multiforme (GBM), 14 had malignant astrocytoma (MA), 6 had
      malignant mixed glioma (MM), and 4 had ependymoma (EP). Porphyrin photosensitizer
      was administered intravenously (i.v.) 12-36 hours prior to photoillumination. All
      patients had the recurrent tumor subtotally resected or cyst drained at surgery
      followed by intraoperative cavitary photoillumination. In 15 cases interstitial
      photoillumination using fibers with 2 cm diffusing tips supplemented the cavitary
      illumination. The total light energy delivered ranged from 440 to 4,500 Joules
      (J) (median = 1,800 J). The energy administered ranged from 120 to 150 J per
      fiber and the linear energy density ranged from 65 to 450 J/cm. The energy
      density ranged from 8 to 110 J/cm2 (median = 38 J/cm2). There were two
      postoperative deaths and three patients were left with a persistent increase in
      their postoperative neurological deficit. The post-PDT median survival of
      patients with recurrent GBM was 30 weeks with a 1- and 2-year actuarial survival
      of 18% and 0%, respectively. The median survival of patients with recurrent GBM
      from first diagnosis was 118 weeks with a 1- and 2-year actuarial survival of 82%
      and 57%, respectively. The post-PDT median survival of patients with recurrent MA
      was 44 weeks with a 1- and 2-year actuarial survival of 43% and 36%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569558
TI  - Use of photodynamic therapy for the management of pleural malignancies.
AB  - Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention
      being investigated for oncologic therapy. Surfaces such as the pleura or the
      peritoneum are frequently involved with primary or metastatic cancer, and the
      chance for cure in such situations is low due to the inability to eradicate all
      the disease. A series of investigations have been performed at the National
      Cancer Institute since 1985 studying the possible use of PDT for large cavity
      treatment. This report details evolution of the methodology, toxicity, and
      overall feasibility of the delivery of intrapleural PDT to patients after
      debulking of primary and malignant chest neoplasms, with an emphasis on malignant
      pleural mesothelioma. These investigations have culminated in an ongoing Phase
      III trial to define the efficacy of intrapleural PDT.

PMID- 7569557
TI  - Photodynamic therapy of head and neck cancers.
AB  - Sixty-five patients with neoplastic diseases of the larynx, oral cavity, pharynx,
      and skin have been treated with photodynamic therapy (PDT) with follow-up to 56
      months. Patients with carcinoma in situ (CIS) and T1 carcinomas obtained a
      complete response after one PDT treatment. All but two have remained free of
      disease. Eight patients with T2 and T3 carcinomas treated with PDT obtained a
      complete response, but they all recurred locally. This is due to the inability to
      adequately deliver laser light to the depths of the tumor bed. Five patients with
      massive neck recurrences of squamous cell carcinomas were treated with
      intraoperative adjuvant PDT following tumor resection. Only one developed
      recurrence with 24-month follow-up. PDT is highly effective for the curative
      treatment of early carcinomas (CIS, T1) of the head and neck. Also,
      intraoperative adjuvant PDT may increase cure rates of large infiltrating
      carcinomas of the head and neck.

PMID- 7569559
TI  - Intracavitary photodynamic therapy for malignant pleural mesothelioma.
AB  - A total of 31 patients with malignant pleural mesothelioma disease, limited to
      one hemithorax, were entered into a phase II study of surgery and intracavitary
      photodynamic therapy. Photofrin, 2 mg/kg, was injected intravenously, and 48
      hours later the patient was taken to the operating room. Bulk tumor was excised
      by a pleuropneumonectomy or pleurectomy. The patient then received 20-25 J/cm2 of
      630 nm light energy from an argon dye laser. The overall estimated median
      survival of patients of all stages was 12 months. Survival of stage III and stage
      IV patients was 8 months. The median survival of 9 patients with stage I and II
      disease was 21 months. We plan to continue this clinical trial; however, entry
      will be limited to patients with stage I and II disease. The light dose for
      photodynamic therapy will be carefully increased to find the maximal tolerated
      dose.

PMID- 7569561
TI  - [Chronic hyperventilation syndrome].
AB  - Hyperventilation syndrome is a frequent, but poorly understood clinical entity.
      The clinical expression is a rich combination of respiratory, cardiac and
      neurological signs which can simulate various organic diseases. Hypocapnia
      remains the primum movens for most authors although the relationship with
      psychiatric situations, in particular in anxious patients, is increasingly
      emphasized. The diagnosis is currently based on the elimination of diseases
      associated with hyperventilation, then on Nijmegen's questionnaire and is
      confirmed by the reproduction of the same clinical picture in a voluntary
      hyperventilation test. Respiratory function tests offer little information.
      Treatment is based on combining rehabilitation therapy focused on the diaphragm
      and on relaxation. Specialized care may be needed in psychiatric patients.

PMID- 7569562
TI  - [Hemoptysis in sarcoidosis. Apropos of 6 cases including 4 with fatal outcome].
AB  - Haemoptysis rarely occurs in sarcoidosis. Most cases usually occur in patients
      with advanced disease and major fibrosis. We observed 6 cases including 5 with
      fibrosis and 1 with inaugural unilateral lymph node involvement. Haemoptysis is a
      sign of gravity since it is the second most frequent cause of death described in
      the literature. In our series 4 of the 6 cases were fatal. Aspergillus
      colonization of a cavity is the most frequently found aggravating factor.
      Ideally, surgery is indicated but usually cannot be performed due to the patients
      respiratory function and the extent of the lesions. Oral drugs have little
      effect. Certain authors have had success with local, initially intrabronchic anti
      aspergillus treatment. CT-guided application is often helpful. Embolization may
      stop the bleeding but in the long-term, a more or less voluminous haemoptysis
      often recurs. Other causes of bleeding are rare. Systemic hypervascularization of
      sarcoidosis lesions has been proposed as one mechanism other than infection. The
      cause may also be a simple granuloma. Symptomatic initial treatment by
      embolization is also proposed in these cases. Finally, massive haemoptysis can
      occur by erosion of the pulmonary artery due to a necrotic sarcoidosis lesion. In
      our series, surgery was impossible in three patients who died. In the three
      others, embolization was possible in 2 and the third underwent successful
      surgery.

PMID- 7569564
TI  - [Treatment of bronchial tumors with high-frequency thermocoagulation. Preliminary
      studies].
AB  - Several techniques are available for endobroncheal tissue destruction. The cost
      and nature of the effect of the different techniques are determining factors in
      deciding on which equipment to use. Electrocoagulation is an old method which has
      practically been abandoned in favour of high frequency coagulation. This
      technique has an immediate effect, somewhat like the laser. We treated 32
      patients with inoperable malignant (17) or benign (5) tumours obstructing the
      trachea or the bronchi. Response to treatment was evaluated on clinical
      manifestations and endoscopic findings. Haemostasis was obtained in 11/12 cases
      and tumour destruction of more than 50% in 27/32 cases. Complications included
      haemoptysia in 2 patients followed by death due to respiratory failure in 1. The
      ERBOTOM ACC 450 equipment was piloted with a microcomputer to control the power
      output automatically. White coagulation was induced by slow heating up to 70-100
      degrees C causing tissue vaporization. The cost of this multiple applications of
      this equipment is competitive.

PMID- 7569563
TI  - [Functional contribution of inhalation spacers in the treatment of asthma].
AB  - The aim of this study is to evaluate the ventilatory gain obtained by using
      metered dose inhaler (MDI) plus spacer versus MDI alone in 30 asthmatic patients
      (19 men and 11 women); aged 30 to 70 years old. Initial spirometry showed air
      flow obstruction. A reversibility test was performed with beta 2 agonists: first
      with MDI and then, later, with MDI plus spacer. In 27 cases (90%) the improvement
      of FEVI, referring to its initial value, was significantly better with spacer.
      This improvement was equal or superior to 20% in 19 patients with spacer versus
      only 9 patients with MDI. The improvement of FEVI was always better with spacer
      which ever the ways of expressing the bronchodilating response (referring to
      initial, predicted or absolute value). in conclusion, since the treatment of
      asthma is now based on local administration of medications, it is recommended to
      use spacers not only for children and patients who have coordination problems but
      more widely specially in severe asthma.

PMID- 7569560
TI  - Photodynamic therapy in Barrett's esophagus: reduction of specialized mucosa,
      ablation of dysplasia, and treatment of superficial esophageal cancer.
AB  - Twelve patients with Barrett's esophagus and dysplasia were treated with
      photodynamic therapy. Five patients also had early, superficial esophageal
      cancers and five had esophageal polyps. Light was delivered via a standard
      diffuser or a centering esophageal balloon. Patients were maintained on
      omeprazole and followed for 6-54 months. In patients with Barrett's esophagus,
      photodynamic therapy ablated dysplastic mucosa and malignant mucosa in patients
      with superficial cancer. Healing and partial replacement of Barrett's mucosa with
      normal squamous epithelium occurred in all patients and complete replacement with
      squamous epithelium was found in three patients. Side effects included
      photosensitivity and mild-moderate chest pain and dysphagia for 5-7 days. In four
      patients with extensive circumferential mucosal ablation in the mid or proximal
      esophagus, healing was associated with esophageal strictures which were treated
      successfully by esophageal dilation. Strictures were not found in the distal
      esophagus. Photodynamic therapy combined with long-term acid inhibition provides
      effective endoscopic therapy of Barrett's mucosal dysplasia and superficial (Tis
      T1) esophageal cancer. The windowed centering balloon improves delivery of
      photodynamic therapy to diffusely abnormal esophageal mucosa.

PMID- 7569565
TI  - [Unilateral agenesis of the pulmonary artery. Diagnosis and therapeutic
      management].
AB  - A case of agenesia of the right pulmonary artery was observed. The
      epidemiological and clinical characteristics of this congenital anomaly as well
      as treatment were reviewed: Surveillance or surgery?

PMID- 7569566
TI  - [Association of sarcoidosis and autoimmune thyroiditis].
AB  - The thyroid gland involvement in sarcoidosis is rare but not exceptional. Usually
      there is little or no clinical expression although hyperthyroidism may be
      present. The granulomatous infiltration of the thyroid gland cannot be
      responsible for all the abnormalities observed. In certain cases, there is
      undoubtedly an autoimmune disease. We report a case of concomitant discovery of
      sarcoidosis and Hashimoto's thyroiditis. Despite their relative frequency, there
      could be a relationship between these two pathologies, especially in light of
      their similar pathophysiology.

PMID- 7569568
TI  - [Acute respiratory insufficiency in a young drug addict of Polynesian origin].

PMID- 7569567
TI  - [Meningococcal pneumonia].
AB  - Meningococci can cause primary bacterial pneumonia. The clinical picture is non
      specific and the clinical course leads to meningeal infection. Diagnosis is based
      on isolation of Neisseria meningitidis in lung samples. Outcome is usually
      favourable.

PMID- 7569569
TI  - [Bullous emphysema and Mycobacterium chelonei].

PMID- 7569570
TI  - [Tuberculosis in France: how to stop the current epidemic? Conference of experts
      on tuberculosis. Paris, 1994 december 15].

PMID- 7569571
TI  - [Epidemiological data. Neonatal and prenatal screening].
AB  - Unlike what is generally thought, cystic fibrosis is not the most frequent
      hereditary disease. Its frequency is approximately 1/3 200 and varies with the
      geographic area. The frequency of heterozygous subjects is about 1/28. No country
      has established a generalized neonatal screening programme, for technical reasons
      and because there has been no demonstration of a beneficial effect from early
      care. It would nevertheless be useful to develop experimental programmes defining
      which protocols might best be established. Antenatal screening can be based on
      detecting heterozygous subjects, a technically feasible operation, although
      answers to a large number of questions would be required.

PMID- 7569573
TI  - [CFTR protein and molecular mechanisms of pulmonary involvement in cystic
      fibrosis].
AB  - Cystic fibrosis is an often fatal hereditary disease mainly affecting the
      epithelium, especially in the airways, the pancreatic ducts, the sudoriparous
      glands and bile ducts. The pathophysiologic mechanism is complex but involves
      abnormal epithelial ion transport which controls water movement through the
      epithelial layers. In the bronchi, there is deficient secretion of chloride
      activated by cyclic AMP and exaggerated sodium absorption which contributes to
      dehydrated bronchial secretion and impaired mucociliary clearance. The cystic
      fibrosis gene was cloned in 1989. It encodes for a protein called cystic fibrosis
      transmembrane conductance regulator or CFTR. This protein belongs to a group of
      proteins which bind ATP and are implicated in ion transportation across
      membranes. The CFTR protein has several functions and is involved in the cyclic
      AMP regulation of the chloride channel. More than 500 mutations of the gene
      encoding for the CFTR protein have been described in cystic fibrosis. The most
      frequent mutation is a phenylalanine deletion in position 508 or delta F508 which
      occurs in approximately 70% of the mutations observed in France. Progress in our
      understanding of the molecular and functional consequences of the different
      mutations has been rapid, but the correlations between each mutation and the
      clinical phenotypes observed have not been fruitful. Many advances in the last
      years using murine models of cystic fibrosis have been developed and clinical
      trials using genetic therapy are now being conducted.

PMID- 7569572
TI  - [Mucoviscidosis: comparative analysis of epidemiological data of French and North
      American registries].
AB  - A national registry for cystic fibrosis was established in France in 1993. A
      questionnaire is sent once a year to different health care units. The first
      questionnaire was analyzed in 1992: 1,893 patients (53% males) were identified.
      28% were over 15 years of age, 13% more than 20, and 1% over 35. Usually,
      diagnosis had been suggested by respiratory signs, followed by digestive tract
      signs and growth impairment and meconial ileus. 13% were diagnosed in screening
      programmes. Diagnosis was made before 1 year in 66% of the subjects (mean = 7
      months). All the data collected and the functional and bacteriologic data were
      compared with those observed in the United States and Canada. It should also be
      noted that 38 patients were grafted during this study year and that it is too
      early to analyze the general outcome for all subjects. The creation of this
      registry is an important step towards a better understanding of the epidemiology
      of cystic fibrosis in the French population.

PMID- 7569574
TI  - [Cystic fibrosis: the CFTR gene, its mutations, the genetic counseling].
AB  - Cystic fibrosis is the most frequent autosomic recessively inherited disease in
      the European population. The gene implicated in this disease was cloned in 1989
      but the consequences of the biochemical defect in the cell have not been fully
      elucidated. To date, 500 mutations of this 230 kilobase gene have been
      identified. These molecular anomalies each have an effect on the encoded protein
      (CFTR) an ion channel which appears to play a role in regulator functions.
      Results of the gene cloning and research into the different mutations have led to
      the development of effective strategies for molecular diagnosis facilitating
      genetic counselling for families at risk and the identification of atypical forms
      of the disease.

PMID- 7569576
TI  - [Mucoviscidosis and nutrition].
AB  - Digestive disorders in patients with cystic fibrosis cause nutritional
      deficiencies which have a major effect on the clinical course and outcome. A
      better understanding of the mechanisms involved and a more adapted therapeutic
      attitude have helped improve the life expectancy in this disease.

PMID- 7569575
TI  - [Mucoviscidosis: in children and adults].
AB  - Because the lifespan of patients with cystic fibrosis is now longer, both
      pediatricians and adult care physicians are involved in the health care strategy.
      Respiratory manifestations occur due to bronchial dilatation and chronic
      bronchial infection, mainly due to Staphylococcus aureus and Pseudomonas.
      Episodes of adult infection are frequent and death usually results from
      respiratory failure. Characteristically, the disease also involves exocrine
      pancreas insufficiency. Other intestinal tract manifestations include meconial
      ileus and liver disease which may reach the stage of biliary cirrhosis.
      Nutritional disorders are frequent. Clinically there are respiratory and
      digestive tract disorders, pansinusitis and frequent nasal polyposis, sometimes
      associated with diabetes mellitus or joint pain. Male sterility results from
      bilateral agenesia of the vas deferens and in the female, fertility is decreased
      although pregnancy is possible. Clinical presentation suggests the diagnosis
      which is confirmed by a sweat test and genetic analysis. Care should be provided
      by a centre specialized in cystic fibrosis. The main treatments rely on
      respiratory physical therapy, antibiotics and gastroprotected pancrease extracts.

PMID- 7569577
TI  - [Pseudomonas aeruginosa and mucoviscidosis].
AB  - Pseudomonas aeruginosa causes episodes of infection which always have a
      deteriorating effect on the clinical course of cystic fibrosis. The factors and
      mechanisms involved were discussed on the basis of data in the literature and the
      experience at the Necker-Enfants-Malades hospital. Preventive measures and
      indications and modalities for treatment are also presented.

PMID- 7569578
TI  - [Bronchopulmonary aspergillosis and mucoviscidosis].
AB  - Patients with cystic fibrosis often suffer from aspergillosis infection
      (basically due to Aspergillus fumigatus) which frequently colonizes their
      respiratory tract, but its role in the respiratory insufficiency are poorly
      understood. Several clinical situations occur. Allergic bronchopulmonary
      aspergillosis rarely occurs in a typical form, and is usually difficult to
      diagnose from the atypical manifestations. Finally indications and treatment
      modalities are still subject to debate.

PMID- 7569579
TI  - [Kinesitherapy for mucoviscidosis].
AB  - Kinesitherapy is an important element in the therapeutic strategy for cystic
      fibrosis. The main objective is to clear the upper airways. The most effective
      and most widely used method is to accelerate expiratory air flow. Kinesitherapy
      should take into account the effect of bronchorrhoea on respiratory mechanics, re
      train the ventilatory process, improve thoracomuscular mechanics, attempt to
      reduce dyspnoea and maintain functional capacity. Managed carefully from
      childhood to adulthood patients should not require ventilatory assistance.
      Patients and/or parents, in cooperation with the medical and para-medical team
      should become fully responsible for correct follow-up and effective treatment.

PMID- 7569580
TI  - [Inflammation, bronchial hyperreactivity and mucoviscidosis].
AB  - Inflammation aggravates respiratory impairment in patients with cystic fibrosis.
      It plays an essential role in the genesis of bronchial hyperreactivity.
      Corticosteroids are the predominant therapeutic agents used. The importance of
      bronchial hyperreactivity in cystic fibrosis is correlated with disease severity.
      Treatment is essential to slow down the progression of bronchiopulmonary
      involvement.

PMID- 7569581
TI  - [Treatment of respiratory insufficiency in mucoviscidosis].
AB  - Cystic fibrosis respiratory disease leads to chronic respiratory insufficiency,
      pulmonary hypertension and cor pulmonale. Clinical evaluation must be helped by
      diurnal arterial gasometry and nocturnal saturation measure, especially in acute
      phase and during the weeks after respiratory infections. Treatment of hypoxemia
      is based on oxygenotherapy, but also on nasal nocturnal ventilation for patients
      waiting for a pulmonary transplantation. Association of them is able to conserve
      or enhance respiratory and nutritional status.

PMID- 7569582
TI  - [Pharmacology of ion channels in mucoviscidosis. Physiological bases and
      therapeutic applications].
AB  - Phenotypical expression of cystic fibrosis (CF) includes decreased epithelial
      chloride secretion and increased sodium absorption. These anomalies produce
      increased water absorption and a dehydrated mucus responsible for decreased
      mucociliary clearance. Identification of the gene responsible for the genetic
      disease (CFTR for cystic fibrosis transmembrane conductance regulator) together
      with a more accurate comprehension of complexes interactions that exist between
      the CFTR gene product and other epithelial ionic channels has created novel
      opportunities for discovering specific pharmacological drugs to treat the
      disease. Amiloride, which limits sodium hyperabsorption, has demonstrated both
      efficacy and safety in vivo in a restricted number of adult patients. Nucleotides
      such as ATP or UTP, prescribed in association with amiloride, increase chloride
      secretion. Potassium channel openers, by stimulating transepithelial chloride
      transport, may represent an additional innovative approach. Specific pharmacology
      to CF is not competitive but rather complementary to gene therapy.

PMID- 7569583
TI  - [New pharmacological approaches: rhDNase].
AB  - rhDNase (Pulmozyme) is a new agent in the therapeutic strategy for patients with
      cystic fibrosis. It is one of the first specific treatments aimed at the
      respiratory tract. It affects the extracellular DNA which is present in abundant
      quantities in the bronchial secretions of these patients. rhDNase significantly
      reduces the incidence of infections and improves respiratory function. It should
      be used as a major treatment in combination with all other treatments in patients
      over 5 years of age with a vital capacity of at least 40% the theoretical value.
      It is important to schedule the respiratory exercises as a function of rhDNase
      intake. The long-term therapeutic benefit remains to be evaluated.

PMID- 7569584
TI  - [Gene therapy in mucoviscidosis].
AB  - Treatment of the respiratory manifestations of cystic fibrosis requires a wide
      therapeutic effort. In this respect, gene therapy is a promising alternative
      approach. Following the cloning of the gene encoding the cystic fibrosis
      transmembrane conductance regulator protein (CFTR), whose malfunction or absence
      lead to the disease phenotype, a particular effort has been undertaken in order
      to validate several gene delivery systems in vitro and in vivo. Recombinant
      adenovirus and adeno-associated virus as well as plasmid DNA associated to
      cationic lipids (liposomes) have been used as vectors. Their efficiency and
      safety have been demonstrated in several animal models. Recombinant adenovirus
      containing the CFTR cDNA (Ad CFTR) and liposomes containing DNA expressing CFTR
      have been instilled into the nose and lungs of several cystic fibrosis patients.
      Aerosol delivery of Ad CFTR has also been performed with success in six patients.
      Transfer of the CFTR gene as well as its expression were demonstrated. In a few
      cases transient correction of the defective transepithelial Cl- transport in the
      cystic fibrosis nasal mucosa was demonstrated. At present several strategies are
      under way to improve the safety and the persistence of CFTR expression of the
      different vector systems.

PMID- 7569586
TI  - [Role of home care in the management of patients with mucoviscidosis].
AB  - Home care, sometimes in the technical form of home hospitalization, is essential
      in caring for patients with cystic fibrosis, both to avoid separating the
      children from their environment and rupturing their life rhythms, but also to
      reduce the risk of hospital contamination. Home care requires an evaluation of
      the disease status, good patient and family information and good coordination
      between the different partners. Thus the reduction in hospitalization greatly
      improves the quality of life in patients with cystic fibrosis.

PMID- 7569585
TI  - [Pulmonary and cardiopulmonary transplantation in mucoviscidosis].
AB  - As early as 1987, several teams in France began lung transplantation for patients
      with cystic fibrosis. Most of these teams propose transplantation when the life
      expectancy is under 2 years. The major functional criteria are VEMS < 30%, PaC02
      > 50 mmHg and PaO2 < 55 mmHg. This contribution focuses on psychologic,
      nutritional and infectious aspects required in preparing the patients for
      transplantation and on graft selection. Surgical techniques and patient care
      after transplantation are also reported. The overall probability of survival
      after transplantation for cystic fibrosis is 48, 35 and 29% at 1, 2 and 3 years
      respectively with wide intercentre variation. The lack of sufficient graft supply
      and the risk of post-transplantation degradation remain the two principal
      problems for transplantation in cystic fibrosis.

PMID- 7569587
TI  - [Variability of bone response to hormone replacement therapy].
AB  - Bone response to hormone replacement therapy (HRT) was assessed in a
      retrospective longitudinal study. 115 women started on HRT for the first time and
      252 controls underwent initial densitometric evaluation (spine and femur) and a
      second evaluation on average 29 months later. Patients were classified as post
      menopausal or perimenopausal according to whether they had had more or less than
      6 months amenorrhea. Oral or non-oral 17-beta estradiol was used at the dose
      generally accepted to be skeletally protective. In the post-menopausal group,
      prescription of HRT was followed by spinal and femoral bone gain (+ 2.85% and +
      1.06% per year respectively). There was no bone gain with HRT in the peri
      menopausal women, but the stability seen contrasted greatly with the very marked
      bone loss found in controls (spine - 3.09% per year and femur - 1.78% per year).
      Lumbar densitometric variations were correlated, at least in the post-menopausal
      group, with those in the femur, but the amplitude of femoral variations was half
      that of the spine. Body mass index (BMI) was not found to be a predictive factor
      of bone response to HRT in this group, but the time since the menopause and
      initial densitometric results were. For the spine, the % of subjects losing their
      bone mass in response to the start of HRT, nil in the post-menopausal group, was
      16% in peri-menopausal women. The % of good responders increased from 8% peri
      menopausally to more than 59% 2 years after the menopause. The response in the
      femur appeared to be very different, with 20% good responders and a % of stable
      subjects similar to that of the control group. Femoral variations and the
      existence regarding the spine of a group showing no or only a poor response to
      HRT would be in favor of densitometric monitoring when initial bone mass is low.

PMID- 7569588
TI  - [Premature rupture of membranes at term. Retrospective study of 88 cases].
AB  - A retrospective study enabled us to evaluate the "wait-and-see" attitude adopted
      in our department in case of premature rupture of the membranes at term. The
      series included 88 patients (9.74%) who delivered spontaneously or after
      induction. The following maternal parameters were studied:time between rupture
      and delivery, pyrexia and chorioamnionitis number of vaginal digital
      examinations, histology and placental bacteriology. Neonatal criteria were based
      upon an infection assessment. Our results showed that approximately 80% of
      patients were in labor within 24 hours following rupture. Cesarean section rate
      remained stable (13%) in comparison with the overall rate for the department.
      Neonatal infectious morbidity (5.7%) showed no increase. The incidence of
      chorioamniotitis did not vary (7 cases) but appeared to be related to the number
      of vaginal examinations before labor. In conclusion, our attitude of
      temporization did not result in any increase in the number of cesarean sections
      nor of neonatal infections in comparison with the general population in the
      department. Prostaglandins might be useful in unfavorable obstetric situations.

PMID- 7569589
TI  - [Value of early oral feeding after a cesarean section].
AB  - In order to evaluate the advantages and possible disadvantages of early oral
      realimentation following cesarean section, the authors undertook a randomized
      prospective study involving 100 patients divided into 2 groups: A, in which oral
      feeding remained forbidden until the spontaneous restoration of intestinal
      function; and B, in which oral feeding was restarted as early as 6 hours
      postoperatively. The results of the study indicate the usefulness of early
      realimentation after cesarean section which, in particular, enabled a 4 hour
      decrease in the time before which flatus was passed and a 5-fold decrease in
      gastrointestinal problems.

PMID- 7569591
TI  - [Vaginal cytology in eating disorders in young girls].
AB  - Critical review of eating disorders in girls, based upon five cases:four of
      anorexia nervosa and one of boulimia, such problems neing accompanied from a
      gynecologic standpoint by amenorrhea. Interpretation of colpocytologic findings,
      differing between cases. Suggestion of the central nervous origin of these
      disorders.

PMID- 7569592
TI  - [Drug treatment of threatened premature labor].
AB  - The problem of the treatment of premature labor has not yet been resolved. The
      positive effect of using sympathomimetics is not as significant as was initially
      thought and they are not free of side-effects. A review of the literature forms
      the basis of a comparison of sympathomimetics with nifedipine and indomethacin.
      The latter sometimes offer a better alternative but must be used with care. The
      potential benefits of oxytocin antagonists are still being evaluated.

PMID- 7569594
TI  - [Genital involvement in a "gloves and socks" syndrome due to parvovirus B19].

PMID- 7569590
TI  - [Postpartum vulvar mass. Diagnostic and therapeutic problems].
AB  - The authors report a case of post-partum unilateral vulval hematoma. The highly
      unusual complication of a thrombosed vulval varicosity.

PMID- 7569593
TI  - [Breast feeding: which contraceptive method?].
AB  - Contraception during breast feeding must take two points into account: the first
      physiological contraception due to anovulation which disappears at around the 9th
      week of lactation); the second pharmacological: any substance ingested by the
      mother during breast feeding is excreted in milk, chiefly by passive diffusion.
      All pharmacokinetic studies have shown that the transfer of progesterone or of
      estrogen when taking a contraceptive pill is extremely slight, being of the same
      order as that of natural hormones. When it is decided to use hormonal
      contraception, this should be started after the 6th week of lactation, when lipid
      profile has returned to normal and thromboembolic risk is identical to that of
      the population in general. As with all prescription during lactation, the drug
      should be taken as far as possible from the next feed. Barrier techniques
      (combining condoms and spermicides) are an elegant alternative to drug methods.

PMID- 7569599
TI  - [Non steroidal anti-inflammatory drugs and rheumatic diseases].
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of
      medicaments that reduced the symptoms of inflamation in rheumatic disease. This
      article emphasizes similarities and class characteristics of the NSAID,
      mechanisms of action, and drug-interactions.

PMID- 7569598
TI  - [Grynfelt's hernia. A case report and review of the literature].
AB  - Lumbar hernias are rare lesions. They involve the extrusion of visceral contents
      through a defect in the posterolateral abdominal wall. Only 250 a 300 cases had
      been reported in the literature. They occur most often in the superior lumbar
      triangle (Grynfelt's hernia). All lumbar hernias must be treated with surgery and
      the preferable surgical approach is done retroperitoneally. Primary repair,
      autologous tissue or prosthetic material may be used to obliterate the defect.
      The authors report a case of Grynfelt's hernia in which polypropylene mesch was
      placed pre-peritonially.

PMID- 7569597
TI  - [Rheumatic involvement in Hansen's disease].
AB  - The classical articular manifestations of Hansen's disease are the neurogenic or
      Charcot's arthropathy, osteitis and specific or non specific osteoarthritis.
      However, inflammatory mechanisms have been associated to arthritic episodes in
      leprosy patients, leading to rheumatoid-like picture as suggested by clinical,
      biopsy and laboratorial data. The extra-articular manifestations also mimicry
      those of some connective tissue diseases. The differencial diagnosis between
      rheumatic syndromes and hanseniasis is important for as early indentification of
      hanseniasis and prevention of severe sequelae and transmission.

PMID- 7569596
TI  - [Comparison between immunofluorescence techniques and ELISA, using whole
      neutrophil extract and primary granules, for the detection of antineutrophil
      cytoplasma antibodies (ANCA)].
AB  - The detection of antineutrophil cytoplasmic antibodies is a very important tool
      for the diagnosis of systemic vasculitis. The specificity and sensitivity of
      these antibodies depends on the assay utilized for their detection. Therefore we
      have compared the immunofluorescence test (IF) with the ELISA using two different
      antigens: total neutrophil extract and isolated primary granules. Two patterns of
      fluorescence were detected by IF: the classic pattern was highly specific for
      Wegener's granulomatosis. In contrast the perinuclear staining correlated with
      renal vasculitis but was also observed in other diseases. However the IF test was
      unable to differentiate low-positive from atypical patterns. Such distinction
      could be achieved by ELISA. The use of ELISA with isolated primary granules is a
      good alternative for if since it has a good specificity, sensitivity and
      reproducibility, moreover it is a quantitative method.

PMID- 7569600
TI  - [The importance of colonoscopy in the early detection of colorectal cancer].
AB  - The rates of surveillance for patients with colorectal cancer have been steady in
      the decades. Aspects regarding the importance of the early detection of the
      colorectal cancer were focussed, as well as the outstanding difference observed
      in relation to the surveillance of patients when the detection of the disease is
      achieved early. It was emphasized the use of colonoscopy as a diagnostic and
      therapeutic method which brings beneficial results to an effective raising in the
      rates of detection of patients with colorectal cancer. It was also demonstrated
      that colonoscopy having a higher accuracy in the diagnosis of the large bowel
      polyps and in the performance of polypectomies, has much contributed to put to an
      end to the cycle described by Morson: the evolution of adenomatous polyp to
      cancer.

PMID- 7569595
TI  - [Progestins and osteoporosis. Does progestin contribute to the effectiveness of
      estrogen replacement therapy in menopause?].

PMID- 7569602
TI  - [The burn ward service at the Hospital das Clinicas, Sao Paulo].

PMID- 7569601
TI  - [Opinion of the people in charge of the medical graduation disciplines at the Sao
      Paulo University Medical School on the 'curriculum evaluation program'].
AB  - Results of "Curricular Evaluation Program" (CEP) of Medical School of S. Paulo
      University (FMUSP) are presented. CEP numbers are obtained form students answers
      offered to a padronized questionnaire which included theoretical and practical
      aspects of curricular process. Authors asked for the opinion of curricular
      disciplines coordinators of FMUSP about CEP and concluded: 1. CEP has large or
      reasonable profitability for 95.3% of coordinators; 2. CEP questionnaire was
      considered adequate by 85.7% of respondents, but 42.8% mentioned deficiencies in
      questionnaire revitance to them; 3. CEP presents excellent performance at FMUSP
      departments level.

PMID- 7569603
TI  - [Characterization of Trypanosoma cruzi strains isolated from patients with heart
      transplantation].
AB  - Three strains of Trypanosoma cruzi were isolated in Chagas' disease patients
      transplanted for heart failure. These strains were studies in an experimental
      model of Chagas' disease, in mice, with evaluation of parasitic load, mortality
      and extension of inflammatory infiltrates in the heart. These parameters were
      compared with those of the standard strain Y. The strains had differences in the
      studies parameters, but there was no clear relationship between them and the post
      transplant evolution of the patients, probably the clinical response is
      multifactorial and derives only in part from biological characteristics of the
      infecting T. cruzi strain, as measured in our model.

PMID- 7569604
TI  - Gelatin particle indirect agglutination test for serodiagnosis of
      schistosomiasis: comparative study with enzyme-linked immunosorbent assay.
AB  - A new serological test, the gelatin particle agglutination test (GPAT), was used
      for the serodiagnosis of schistosomiasis mansoni. This technique showed the
      sensitivity (90.6%) and specificity (97.8%) close to those of enzyme-linked
      immunosorbent assay. The GPAT can be easily and rapidly performed without
      specialized equipment, by using lyophilized antigen-coated gelatin particles. The
      test also seems to be useful for mass screening of Schistosoma infection in field
      conditions.

PMID- 7569605
TI  - [Immunological aspects of the phenoloxidase enzymatic system of Schistosoma
      mansoni].
AB  - The phenol oxidase enzymatic system (EC 1.10.3.1, EC 1.10.3.2) is widespread in
      different species of the animal and vegetal kingdom. Despite its importance in
      the eggshell formation of the trematodes phenol oxidase (PO) has been little
      studied in these organisms, mainly in S. mansoni. This report presents the
      initial results concerning the immunization of rabbits with PO of S. mansoni and
      mushroom tyrosinase. The immunological analysis done by means of double
      immunodifusion (Ouchterlony) and immunoelectrophoresis techniques revealed some
      immunological identity between the PO of males and females. It was not seen cross
      reaction between the antisera against PO and tyrosinase, what suggests that the
      antigenic determinants of both enzymes are different in spite of their catalytic
      sites being similar, since they act over the same substrate. The results reported
      here represent a first step in way to obtain the PO isoenzymes in their pure form
      and should open new insights for further studies on the molecular mechanisms
      involved in the sclerotization process of the S. mansoni eggshell.

PMID- 7569607
TI  - [Susceptibility of Biomphalaria tenagophila and Biomphalaria glabrata from a same
      region to 2 Schistosoma mansoni strains].
AB  - B. tenagophila snails from Ouro Branco, MG, showed positivity for S. mansoni,
      with infection rates of 5%, 10%, (SJ strain), and 1% (LE strain) using a pool of
      miracidia. The mollusks were found to be susceptive from the 3rd generation
      reared in laboratory onwards. The B. tenagophila (OB, MG) when individually
      exposed to 10 miracidia, showed infection rate of 2% for LE strain. B. glabrata
      snails from Gage, MG, showed a positivity rate of 58% for S. mansoni (LE strain),
      under experimental conditions. The B. tenagophila from Cabo Frio, RJ and B.
      glabrata from Belo Horizonte, MG used as a control for SJ strain showed infection
      rates of 47%-85% and 36% respectivily. For the LE strain, B. glabrata (BH, MG)
      used as control showed infection rate of 40%-75%.

PMID- 7569606
TI  - Cutaneous Nocardia asteroides infection of nontraumatic origin.
AB  - This paper reports a case of cutaneous infection of nontraumatic origin caused by
      Nocardia asteroides in a hospitalized patient with chronic obstructive pulmonary
      disease. Diagnosis was established by direct and histological examination,
      cultures from exudate and biopsy specimen. We discuss the classification of
      clinical forms of Nocardia infections affecting the skin.

PMID- 7569611
TI  - [Malacological survey of the Soledade lake hydrographic basin, in Ouro Branco
      (Minas Gerais, Brazil)].
AB  - A malacological survey was carried out at the Soledade Lake, in Ouro Branco,
      State of Minas Gerais, for the period 1986-1991. A total amount of 46,579
      mollusks was collected, and among them seven species corresponding to five
      families could be found, as follows: 39,176 specimens of Biomphalaria
      tenagophila; 1,296 B. glabrata; 7 Drepanotrema cimex; 2,527 Physa sp; 417 Lymnaea
      sp; 92 Pomacea hastrum, and 3,064 specimens of Melanoides tuberculata
      (Melanniidae = Thiaridae) were collected from March/1990 onwards. Four specimens
      of B. tenagophila were found to be positive for Schistosoma mansoni.

PMID- 7569608
TI  - [Prospective study with infants whose mothers had dengue during pregnancy].
AB  - Dengue congenital disease was not confirmed in 10 children whose mothers had the
      infection during pregnancy. The fetal sera presented anti-dengue IgG antibodies
      which progressively declined, and disappeared after 8 months. IgM antibodies to
      dengue were not observed in the sera. Other normal data suggesting the healthy
      state of the children included: absence of malformations, pregnancy time, Apgar
      index, weight, and placenta aspect.

PMID- 7569610
TI  - Prevalence of thermotolerant species of Campylobacter and their biotypes in
      children and domestic birds and dogs in southern Chile.
AB  - The prevalence of thermotolerant Campylobacter in diarrhoeic and healthy children
      as well as in dogs, hens, ducks and pigeons was determined in Southern Chile.
      Campylobacter were found in 34.5% of the faecal samples examined. The isolation
      rate of Campylobacter in diarrhoeic and healthy children was 16.3% and 6.4%
      respectively. Despite C. jejuni was always more frequent than C. coli, the latter
      was isolated with a high frequency (29%) from patients with diarrhoea. C. jejuni
      and C. coli biotypes I and II were found in healthy and diarrhoeic children and
      were predominant in all the animals species studied. This may point out towards
      the possible origin of strains infecting children.

PMID- 7569609
TI  - Murine virus contaminant of Trypanosoma cruzi experimental infection.
AB  - The possibility that some virus contaminants could be altering host response to
      Trypanosoma cruzi experimental infection was investigated. Data obtained showed
      that CBA/J mice infected with stocks of parasite maintained in mice (YIUEC)
      presented higher level of parasitemia and shorter survival times than those
      infected with a stock (YITC) which was also maintained in mice but had been
      previously passaged in cell culture. Mouse antibody production tests, performed
      with the filtered plasma of mice infected with YIUEC, indicated the presence of
      mouse hepatitis virus (MHV) while no virus was detected when testing the plasma
      of YITC infected mice. Filtered plasma of YIEUC infected mice was shown to
      contain a factor able to enhance the level of parasitemia and to reduce the mean
      survival time of mice challenged with 10(5) YITC. This factor, that could be
      serially passaged to naive mice was shown to be a coronavirus by neutralization
      tests.

PMID- 7569612
TI  - [Prevalence of toxoplasmosis in pregnant women of the province of La Habana].
AB  - A seroepidemiological study of Toxoplasma gondii was carried out in four
      municipalities of Havana Province from October 1990 to April 1991 using a 10
      microL ultra micro-ELISA. We tested 362 serum samples, from pregnant women, and
      71% of toxoplasmic infection was found. Toxoplasmic infection was more frequent
      in women living in rural zones having domestic contacts with cats. The
      relationship of toxoplasmic infection and spontaneous abortion antecedent in this
      group was analyzed but no statistically significant differences were found.

PMID- 7569613
TI  - [Snake bites in children: antivenom early reaction frequency in patients
      pretreated with histamine antagonists H1 and H2 and hydrocortisone].
AB  - Type and frequency of early reactions (ER) were studied in 24 children aging 2-14
      years victims of snake bites who received pretreatment with histamine antagonists
      H1 (dextrochlorfeniramine) and H2 (cimetidine or ranitidine) and hydrocortisone
      from 1989 to 1993. None of them had atopy nor received any type of anti
      venoms(AV) and antitoxins before. Of 24 children, 15 received bothropic AV (ER in
      5), 7 crotalic AV (ER in 5), 1 crotalic plus crotalic-bothropic AV, and 1
      elapidic AV (ER in 1). In 3 children severe early reactions were observed and
      they were classified as severe crotalic accident. Results suggest that pre
      treatment did not offer safety protection at the appearance of early reactions.

PMID- 7569614
TI  - [Histopathology of the localized form of cutaneous leishmaniasis caused by
      Leishmania (Leishmania) amazonensis].
AB  - The microscopic changes found in the localized form of the human cutaneous
      leishmaniasis due to Leishmania (Leishmania) amazonensis are reported. In this
      form, less known than the diffuse one caused by the same species, the clinical
      manifestations are identical to those produced by other Leishmania species of the
      subgenus Viannia. There is, however, in the localized infection by L. (L.)
      amazonensis, a peculiar feature, only recently discovered: about 50% of the
      affected individuals are Montenegro-negatives. The main histologic change
      observed in the skin sections was the presence of groups of macrophages with a
      large vacuole in the cytoplasm, containing many amastigotes. The microscopic
      picture is similar to that found in the diffuse form of the disease, the
      difference being only quantitative. When in large numbers, the macrophages
      suffers necrosis, which generally starts at the center of the groups. First, in
      this process, the membrane of the parasitized cells ruptures, and the amastigotes
      become free; later, both cells and parasites are destroyed. The picture can be
      seen either in Montenegro-negative or in Montenegro-positive patients. The
      macrophages with amastigotes may persist in tissues for as long as 6-7 months,
      while in the infections due to L. (V.) braziliensis the parasites usually
      disappear in a few weeks.

PMID- 7569616
TI  - [Possibility of spontaneous cure in opossums (Didelphis albiventris) naturally
      infected by Trypanosoma cruzi].

PMID- 7569618
TI  - Acute-phase response in snakebite.

PMID- 7569615
TI  - Aspergillosis in immunocompromised children with acute myeloid leukemia and bone
      marrow aplasia. Report of two cases.
AB  - Two cases of Aspergillosis in immunocompromised children are reported. Both were
      caused by Aspergillus flavus. Early diagnosis and treatment led to the remission
      of the process. One patient had acute myeloid leukemia; the fungus was isolated
      from the blood. The other patient with bone marrow aplasia, presented an invasive
      aspergillosis of the paranasal sinuses with dissemination of fungal infection;
      the diagnosis was obtained by histology and culture of biopsied tissue from a
      palatal ulceration.

PMID- 7569617
TI  - Dot-ELISA-IgM in saliva for the diagnosis of human leptospirosis using polyester
      fabric-resin as support (preliminary report).
AB  - In order to improve the diagnosis of human leptospirosis, we standardized the dot
      ELISA for the search of specific IgM antibodies in saliva. Saliva and serum
      samples were collected simultaneously from 20 patients with the icterohemorrhagic
      form of the disease, from 10 patients with other pathologies and from 5 negative
      controls. Leptospires of serovars icterohaemorrhagiae, canicola, hebdomadis,
      brasiliensis and cynopteri grown in EMJH medium and mixed together in equal
      volumes, were used as antigen at individual protein concentration of 0.2
      micrograms/microliters. In the solid phase of the test we used polyester fabric
      impregnated with N-methylolacrylamide resin. The antigen volume for each test was
      1 microliter, the saliva volume was 8 microliters, and the volume of peroxidase
      labelled anti-human IgM conjugate was 30 microliters. A visual reading was taken
      after development in freshly prepared chromogen solution. In contrast to the
      classic nitrocellulose membrane support, the fabric support is easy to obtain and
      to handle. Saliva can be collected directly onto the support, a fact that
      facilitates the method and reduces the expenses and risks related to blood
      processing.

PMID- 7569619
TI  - Investigation on the possibility of spontaneous cure of mice infected with
      different strains of Trypanosoma cruzi.
AB  - Seventy Swiss mice chronically infected with different strains of Trypanosoma
      cruzi, with persistently negative parasitemia on routine blood examination were
      parasitologically investigated to find out whether spontaneous cure occurred.
      Duration of infection varied from 90 to 250 days in the initial phase of this
      investigation. Parasitological tests consisted of daily direct blood examination
      performed during at least 25 days, followed by xenodiagnosis and subinoculation
      of blood into newborn mice. Mice that persisted negative were treated with
      Cyclophosphamide with one dose of 250 mg/kg of body weight and then investigated
      by direct blood examination, xenodiagnosis and subinoculation. A second dose of
      250 mg/kg b. w. was given to the persistently negative mice. With one single
      exception, all mice showed positive parasitological tests in the different stages
      of the present investigation and we conclude that spontaneous cure did not occur
      in this group, which is representative of the chronic infection with different
      strains of T. cruzi.

PMID- 7569622
TI  - Chicken as potential contamination source of Campylobacter lari in Iquitos, Peru.
AB  - In order to know the importance of chicken as natural reservoir of Campylobacter
      lari in Iquitos, Peru; samples were obtained by cloacal swabs from 200 chickens
      and immediately placed into a semisolid enrichment medium; these were streaked on
      modified Skirrow Agar. The organism was isolated from 21 (10.5%) samples,
      corresponding 58.8% to biovar I and 41.2% to biovar II (Lior scheme). The results
      provide evidence that chicken appear to be prominent reservoirs of Campylobacter
      lari in Iquitos.

PMID- 7569621
TI  - Bacterial agents isolated from cerebrospinal fluid of patients with acquired
      immunodeficiency syndrome (AIDS) and neurological complications.
AB  - Cerebrospinal fluid (CSF) samples from 2083 patients with acquired
      immunodeficiency syndrome (AIDS) and neurological complications were
      bacteriologically examined during a period of 7 years (1984-1990). The percentage
      of patients who had at least one bacterial agent cultured from the CSF was 6.2%.
      Mycobacterium tuberculosis was the most frequently isolated agent (4.3%),
      followed by Mycobacterium avium complex or MAC (0.7%), Pseudomonas spp (0.5%),
      Enterobacter spp (0.4%), and Staphylococcus aureus (0.3%). Among 130 culture
      positive patients, 89 (68.5%) had M. tuberculosis and 15 (11.6%) had MAC. The
      frequency of bacterial isolations increased from 1988 (5.2%) to 1990 (7.2%),
      partly due to the increase in MAC isolations. Bacterial agents were more
      frequently isolated from patients in the age group 21-30 years and from women (p
      < 0.05).

PMID- 7569623
TI  - Anti-HCV related to HCV PCR and risk factors analysis in a blood donor population
      of central Brazil.
AB  - Data concerning HCV infection in Central Brazil are rare. Upon testing 2,350
      voluntary blood donors from this region, we found anti-HCV prevalence rates of
      2.2% by a second generation ELISA and 1.4% after confirmation by a line
      immunoassay. Antibodies against core, NS4, and NS5 antigens of HCV were detected
      in 81.8%, 72.7%, and 57.5%, respectively, of the positive samples in the line
      immunoassay. HCV viremia was present in 76.6% of the anti-HCV-positive blood
      donors. A relation was observed between PCR positivity and serum reactivity in
      recognizing different HCV antigens in the line immunoassay. The majority of the
      positive donors had history of previous parenteral exposure. While the
      combination of ALT > 50 IU/l and anti-HBc positivity do not appear to be good
      surrogate markers for HCV infection, the use of both ALT anti-HCV tests is
      indicated in the screening of Brazilian blood donors.

PMID- 7569620
TI  - Production of Schistosoma mansoni cercariae by Biomphalaria glabrata from a focus
      in Belo Horizonte, Minas Gerais.
AB  - The snail density, levels of infection and the monthly production of Schistosoma
      mansoni cercariae by Biomphalaria glabrata were determined in a focus of Barreiro
      de Baixo (Belo Horizonte, MG, Brazil). During a period of 38 months (1984 to
      1987) 5,366 snails were collected of which 324 (6.03%) were infected with S.
      mansoni. The total number of cercariae shed was 5,667,312. Each snail shed an
      average of 17,422 cercariae during the time that it was under study in the
      laboratory. The greatest longevity of infected snails was 218 days. Natural cure
      was observed in 42 (12.9%) of the infected specimens about 130 days after
      collection. The average snail density in the focus during the period of study was
      16.3 snails per scoop. The shedding of cercariae by snails collected from the
      field was compared with laboratory bred specimens infected in mass with the LE
      strain of S. mansoni from Belo Horizonte. The laboratory infected snails shed an
      average of 6,061 cercariae each, a value 2.8 times less than the field specimens
      due to a shorter life span. The prevalence of schistosomiasis in the focus was
      14.3%.

PMID- 7569625
TI  - Chagas' infection in university students of Santa Cruz de la Sierra, Bolivia. A
      serologic-electrocardiographic study.
AB  - In order to learn the prevalence of Chagas' infection among students from Santa
      Cruz de la Sierra's universities, a random sample of 372 new students was drawn.
      All participants have had electrocardiograms (EKG) and serologic analysis (IHAT).
      64/372 (17.2%) had serologic evidence of Chagas' infection, and from those, 10/64
      (15.6%) had some EKG alterations. Among students presenting negative serologic
      test, 31/308 (10.1%) had EKG alterations. There was no statistical association
      between Chagas' infection and EKG alterations (X2 = 1.67, p = 0.2). There was a
      positive association between Chagas' infection and intraventricular conduction
      defects and this association was higher among the students of 19 years of age or
      less (O.R. 10.4, p < 0.05).

PMID- 7569624
TI  - Erythema nodosum: prospective study of 32 cases.
AB  - The results of 32 cases studied lead us to the conclusion that erythema nodosum's
      investigation routine is very important, once in our retrospective study, the
      percentage of cases of unknown etiology was 69.4%, and in this prospective study
      it is 21.8%. In 10 cases (31.2%), more than one causing agent was suspected.
      Infections (bacterial, helminthic, fungal, by protozoa) were diagnosed in 26
      cases, streptococcal infection having predominated (12 cases). Drugs-dipirone,
      aspirin, anovulatory--were suspected as causing agents in 13 cases. The
      association of erythema nodosum and histoplasmosis capsulata is described for the
      first time in Brazil. We consider erythema nodosum to be a complex syndrome which
      should be regarded as a manifestation of underlying diseases. The fact that all
      32 subjects were women, 26 of them during menacme, suggests that particular
      hormonal media may favor the action of various processes (infections and drugs),
      precipitating erythema nodosum's clinical picture.

PMID- 7569628
TI  - Dot-enzyme-linked immunosorbent assay (Dot-ELISA) for detection of pneumococcal
      polysaccharide antigens in pleural fluid effusion samples. Comparison with
      bacterial culture, counterimmunoelectrophoresis and latex agglutination.
AB  - A dot-enzyme-linked immunosorbent assay (Dot-ELISA) for pneumococcal antigen
      detection was standardized in view of the need for a rapid and accurate
      immunodiagnosis of acute pneumococcal pneumonia. A total of 442 pleural fluid
      effusion samples (PFES) from children with clinical and laboratory diagnoses of
      acute bacterial pneumonia, plus 38 control PFES from tuberculosis patients and 20
      negative control serum samples from healthy children were evaluated by Dot-ELISA.
      The samples were previously treated with 0.1M EDTA pH 7.5 at 90 degrees C for 10
      min and dotted on nitrocellulose membrane. Pneumococcal omniserum diluted at
      1:200 was employed in this assay for antigen detection. When compared with
      standard bacterial culture, counterimmunoelectrophoresis and latex agglutination
      techniques, the Dot-ELISA results showed relative indices of 0.940 to
      sensitivity, 0.830 to specificity and 0.760 to agreement. Pneumococcal omniserum
      proved to be an optimal polyvalent antiserum for the detection of pneumococcal
      antigen by Dot-ELISA. Dot-ELISA proved to be a practical alternative technique
      for the diagnosis of pneumococcal pneumonia.

PMID- 7569629
TI  - Entamoeba histolytica: detection of coproantigens by purified antibody in the
      capture sandwich ELISA.
AB  - A sensitive and specific Capture Sandwich ELISA (CSE) was developed using
      polyclonal purified rabbit antibodies against three different axenic strains of
      Entamoeba histolytica: CSP from Brazil and HM1 - IMSS from Mexico, for the
      detection of coproantigens in fecal samples. Immunoglobulin G (IgG) against E.
      histolytica was isolated from rabbits immunized with throphozoites whole extract
      in two stages: affinity chromatography in a column containing E. histolytica
      antigens bound to Sepharose 4B was followed by another chromatography in
      Sepharose antibodies 4B-Protein A. A Capture Sandwich ELISA using purified
      antibodies was able to detect 70ng of amebae protein, showing a sensitivity of
      93% and specificity of 94%. The combination of microscopic examination and CSE
      gave a concordance and discordance of 93.25% and 6.75%, respectively. It was
      concluded that CSE is highly specific for the detection of coproantigens of E.
      histolytica in feces of infected patients, is quicker to perform, easier and more
      sensitive than microscopic examination.

PMID- 7569626
TI  - Prevalence and pathogenicity of Entamoeba histolytica in three different regions
      of Pernambuco, northeast Brazil.
AB  - Parasitological examinations were carried out on 663 individuals of three
      different cities of Pernambuco State, Northeastern Brazil: Recife, Palmares and
      Bodoco. The population from a drought area of Pernambuco State, Bodoco, was
      investigated for amoebiasis and compared with Recife, metropolitan city (about
      1.3 million of inhabitants) and another inland community, Palmares, located
      inside of the sugar-cane plantation region of the State. No evidence of invasive
      strains of E. histolytica were found in these inhabitants, provided that the
      isolated zymodemes I, III, IV, VIII, IX, X, XVII and XVIII are recognized as
      nonpathogenic strains of E. histolytica. Furthermore, the prevalence of
      intestinal helminths and other protozoan infections showed that these individuals
      are infected by other agents responsible for diarrhoeal diseases.

PMID- 7569627
TI  - Usefulness of the detection of Toxoplasma gondii antigens in AIDS patients.
AB  - Toxoplasmic encephalitis (TE) is a mayor cause of central nervous system
      infection in patients with acquired immunodeficiency syndrome (AIDS). Toxoplasma
      antibodies were detected in 56 of 79 patients with AIDS (71%), in the present
      study. Fourteen out of 57 seropositive patients developed TF (25%) and had
      Toxoplasma gondii antigen detected in their urine. For this, most of them
      received an effective therapy, with the subsequent disappearance of the symptoms
      and discontinuity of excretion of the T. gondii antigens. Our results suggest
      that the monitoring of T. gondii antigen in the urine of AIDS patients may be
      useful to decide on the proper time for therapy, as well as to avoid the
      beginning of neurologic signs in these patients.

PMID- 7569630
TI  - Low intrafamilial transmission of hepatitis C virus in central Brazil.

PMID- 7569631
TI  - Flucytosine+fluconazole association in the treatment of a murine experimental
      model of cryptococcosis.
AB  - The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the
      treatment of a murine experimental model of cryptococcosis, was evaluated. Seven
      groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells
      of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg)
      and FLU (16 mg/kg), either combined and individually, by daily gavage beginning 5
      days after the infection, for 2 and 4 weeks. One group received distilled water
      and was used as control. The evaluation of treatments was based on: survival
      time; macroscopic examination of brain, lungs, liver and spleen at autopsy;
      presence of capsulated yeasts in microscopic examination of wet preparations of
      these organs and cultures of brain homogenate. 5-FC and FLU, individually or
      combined, significantly prolonged the survival time of the treated animals with
      respect to the control group (p < 0.01). Animals treated for 4 weeks survived
      significantly longer than those treated for 2 weeks (p < 0.01). No significant
      differences between the animals treated with 5-FC and FLU combined or separately
      were observed in the survival time and morphological parameters. The association
      of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the
      treatment of this experimental model of cryptococcosis.

PMID- 7569632
TI  - Ethical guidelines for FAPESP-sponsored research on human populations. Group on
      Bioethics and Population Research.

PMID- 7569633
TI  - [Relationship between histoplasmin skin test and antibody levels detectable by
      ELISA and immunodiffusion].

PMID- 7569634
TI  - Monoclonal antibody to serotype 17 of Neisseria meningitidis and their prevalence
      in Brazilian states.
AB  - Neisseria meningitidis are gram-negative diplococci responsible for cases of
      meningococcal disease all over the world. The epidemic potential of N.
      meningitidis serogroup B and C is clearly a function of their serotype antigens
      more than of their capsular polysaccharides. Until recently, hiperimmune sera
      were used to detect typing antigens on the bacteria. The advent of monoclonal
      antibodies (MAbs) offered the opportunity to eliminate many of the cross
      reactions and have improved the accuracy and reproducibility of meningococcal
      serotyping. We have produced a MAb to the outer membrane protein of the already
      existent serotype 17 that have been detected by the use of hiperimmune rabbit
      sera. The prevalence of this serotype epitope is low in the Brazilian strains. By
      using the MAb 17 we could not decrease the percentage of nontypeable serogroup C
      strains. However, there were a decreasing in nontypeable strains to 13% into
      serogroup B strains and to 25% into the other serogroups.

PMID- 7569635
TI  - Prevalence of intestinal parasitic infection in five farms in Holambra, Sao
      Paulo, Brazil.
AB  - A parasitological survey was carried out on 222 inhabitants of five farms in
      Holambra, located 30 km north of Campinas, Sao Paulo, Brazil, on October 1992.
      Approximately 70% of the inhabitants were found to be infected with at least one
      species of intestinal parasite. The positive rates of 6 helminths and 7 protozoan
      species detected are as follows: 5.4% Ascaris lumbricoides; 8.6% Trichuris
      trichiura; 19.8% Necator americanus; 10.4% Strongyloides stercoralis; 1.4%
      Enterobius vermicularis; 0.9% Hymenolepis nana; 3.2% Entamoeba histolytica; 2.7%
      E. hartmanni; 9.9% E. coli; 14.0% Endolimax nana; 2.3% Iodamoeba butschlii; 10.4%
      Giardia lamblia; 37.8% Blastocystis hominis. The positive rates of helminth
      infection were generaly higher in the younger-group under 16 years-old than those
      in the elder group aged 16 or more, whereas the infection rates of protozoan
      species were higher in the elder group. The infection rate of Strongyloides was
      found to be 10.4% by a newly developed sensitive method (an agarplate culture
      methods).

PMID- 7569637
TI  - Cell and humoral immunity in endemic pemphigus foliaceus.
AB  - A study was conducted on 16 patients with pemphigus foliaceus, ten of them with
      the localized form (group G1) and six with the disseminated form (group G2).
      These patients were submitted to full blood counts, quantitation of mononuclear
      cell subpopulations by monoclonal antibodies, study of blastic lymphocyte
      transformation, and quantitation of circulating antibodies by the indirect
      immunofluorescence test, in order to correlate their clinical signs and symptoms
      and laboratory data with their immunological profile, and to determine the
      relationship between circulating autoantibody titers and lesion intensity and
      course of lesions under treatment. Leucocytosis was observed especially in group
      G2. All patients showed decreased relative CD3+ and CD4+ values and a tendency to
      decreased relative values of the CD8+ subpopulation. Blastic lymphocyte
      transformation indices in the presence of phytohemagglutinin were higher in
      patients (group G1 + G2) than in controls. The indirect immunofluorescence test
      was positive in 100% of G2 patients and in 80% of G1 patients. The median value
      for the titers was higher in group G2 than in group G1. Analysis of the results
      as a whole permits us to conclude that cell immunity was preserved and that there
      was a relationship between antibody titers detected by the direct
      immunofluorescence test and extent of skin lesions.

PMID- 7569636
TI  - The malarial impact on the nutritional status of Amazonian adult subjects.
AB  - The anthropometric (body weight, height, upper arm circumference, triceps and
      subescapular skinfolds; Quetelet index and arm muscle circumference) and blood
      biochemistry (proteins and lipids) parameters were evaluated in 93 males and 27
      females, 17-72 years old voluntaries living in the malarial endemic area of
      Humaita city (southwest Amazon). According to their malarial history they were
      assembled in four different groups: G1--controls without malarial history (n:30);
      G2--controls with malarial history but without actual manifestation of the
      disease (n:40); G3--patients with Plasmodium vivax (n:19) and G4--patients with
      Plasmodium falciparum (n:31). The malarial status was stablished by clinical and
      laboratory findings. The overall data of anthropometry and blood biochemistry
      discriminated the groups differently. The anthropometric data were low sensitive
      and contrasted only the two extremes (G1 > G4) whereas the biochemistry
      differentiated two big groups, the healthy (G1 + G2) and the patients (G3 + G4).
      The nutritional status of the P. falciparum patients was highly depressed for
      most of the studied indices but none was sensitive enough to differentiate this
      group from the P. vivax group (G3). On the other hand the two healthy groups
      could be differentiated through the levels of ceruloplasmin (G1 < G2) and alpha
      nitrogen (G1 > G2). Thus it seems that the malaria-malnourishment state exists
      and the results could be framed either as a consequence of nutrient sink and/or
      the infection stress both motivated by the parasite.

PMID- 7569638
TI  - Serodiagnosis of strongyloidiasis. The application and significance.
AB  - Parasitological diagnosis based on the faecal examination is frequently difficult
      in cases of chronic, low-level S. stercoralis infection. Even when a newly
      developed sensitive method (an agar plate culture) is applied, it is essential to
      examine faecal samples repeatedly to achieve a correct diagnosis. Additionally,
      it is important to note that a negative result does not necessarily indicate the
      unequivocal absence of the infection. On the other hand, several serological
      tests which have recently been developed for strongyloidiasis have proven
      reliable when used to complement parasitological examination. We have developed
      two serological tests, ELISA and GPAT, to demonstrate Strongyloides infection and
      possible applications of the serological tests for diagnosis, mass-screening,
      epidemiological study and postchemotherapy evaluation of strongyloidiasis were
      reviewed based on our recent studies.

PMID- 7569640
TI  - Evaluation of nutritional status in patients with endemic pemphigus foliaceus.
AB  - Sixteen patients with endemic pemphigus foliaceus were submitted to nutritional
      evaluation. Ten had the localized form of the disease (Group G1) and six the
      disseminated form (Group G2). The patients were submitted to anthropometric
      measurements (weight, height, Quetelet index, tricipital skin fold, subscapular
      skin fold, arm circumference, arm muscle circumference, arm area, arm muscle
      area, and arm adipose area) and to laboratory evaluation by protein
      electrophoresis. Arm circumference, arm area and arm muscle area showed lower
      values in G2 than in G1. Weight and arm muscle circumference tended to the lower
      in G2 than in G1. Protein electrophoresis showed decreased albumin levels in both
      groups, with lower values in G2. Overall analysis of the results permits us to
      conclude that patients with endemic pemphigus foliaceus present signs and
      symptoms of protein, but not calorie, malnutrition and that this malnutrition is
      more marked in patients with disseminated pemphigus foliaceus.

PMID- 7569641
TI  - Cardiac beta-receptors in experimental Chagas' disease.
AB  - Experimental Chagas' disease (45 to 90 days post-infection) showed serious
      cardiac alterations in the contractility and in the pharmacological response to
      beta adrenergic receptors in normal and T. cruzi infected mice (post-acute
      phase). Chagasic infection did not change the beta receptors density (78.591 +/-
      3.125 fmol/mg protein and 73.647 +/- 2.194 fmol/mg protein for controls) but
      their affinity was significantly diminished (Kd = 7.299 +/- 0.426 significantly
      diminished (Kd = 7.299 +/- 0.426 nM and Kd = 3.759 +/- 0.212 nM for the control)
      p < 0.001. This results demonstrate that the alterations in pharmacological
      response previously reported in chagasic myocardium are related to a
      significantly less beta cardiac receptor affinity. During this experimental
      period serious cardiac cell alterations take place and functional consequences
      will be detected in the chronic phase.

PMID- 7569642
TI  - Liver dysfunction in patients bitten by Crotalus Durissus terrificus (Laurenti,
      1768) snakes in Botucatu (State of Sao Paulo, Brazil).
AB  - Thirty-two patients bitten by venomous snakes sixteen by Bothrops spp. and
      sixteen by Crotalus durissus terrificus were studied. The group comprised thirty
      males and two females, aged eight to sixty-three years (mean 33 +/- 15).
      Bromsulphalein tests were increased in the majority of patients bitten by
      Crotalus durissus terrificus. The correlation coefficient of Spearman was
      positive between bromsulphalein tests and alanine aminotransferase levels, and
      between alanine aminotransferase and aspartate aminotransferase levels only in
      the Crotalus group. The only patient who died was bitten by Crotalus durissus
      terrificus and showed hydropic degeneration and mitochondrial injury in the
      liver. It was concluded that the hepatic damage might have been caused by at
      least two possible mechanisms: venom effect on liver mitochondria and cytokine
      effects on hepatocyte, specially interleukin-6.

PMID- 7569643
TI  - Pattern of mycobacterial antigen detection in leprosy.
AB  - Immunohistochemistry reaction (Peroxidase anti-peroxidase--PAP) was carried out
      on fifty-two skin biopsies from leprosy patients with the purpose to identify the
      antigenic pattern in mycobacteria and to study the sensitivity of this method.
      Five different patterns were found: bacillar, granular, vesicular, cytoplasmatic
      and deposits, classified according to the antigenic material characteristics.
      Deposits (thinely particulate material) appeared more frequently, confirming the
      immunohistochemistry sensitivity to detect small amounts of antigens even when
      this material is not detected by histochemical stainings.

PMID- 7569644
TI  - Standardization of an enzyme linked immunosorbent assay (ELISA) for detecting
      circulating toxic venom antigens in patients stung by the scorpion Tityus
      serrulatus.
AB  - The sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA)
      for the detection of circulating antigens from toxic components of Tityus
      serrulatus scorpion venom was determined in patients stung by T. serrulatus
      before antivenom administration. Thirty-seven patients were classified as mild
      cases and 19 as moderate or severe cases. The control absorbance in the venom
      assay was provided by serum samples from 100 individuals of same socioeconomic
      group and geographical area who had never been stung by scorpions or treated with
      horse antisera. The negative cutoff value (mean + 2 SD) corresponded to a venom
      concentration of 4.8 ng/ml. Three out of the 100 normal sera were positive,
      resulting in a specificity of 97%. The sensitivity of the ELISA when all cases of
      scorpion sting were included was 39.3%. When mild cases were excluded, the
      sensitivity increased to 94.7%. This study showed that this ELISA can be used for
      the detection of circulating venom toxic antigens in patients with systemic
      manifestations following. T. serrulatus sting but cannot be used for clinical
      studies in mild cases of envenoming since the test does not discriminate mild
      cases from control patients.

PMID- 7569645
TI  - High prevalence of hepatitis C infection among Brazilian hemodialysis patients in
      Rio de Janeiro: a one-year follow-up study.
AB  - Nearly 400 hemodialysis patients treated at 5 different hemodialysis units in Rio
      de Janeiro were tested for one year for the presence of hepatitis C and B
      markers. During the same period, samples were also obtained from 35 continuous
      ambulatory peritoneal dialysis (CAPD) patients and from 242 health care workers.
      Depending on the hemodialysis unit studied, anti-HCV prevalence rates ranging
      from 47% to 82% (mean 65%) were detected. CAPD patients showed a lower prevalence
      of 17%. The prevalence of antibodies against hepatitis C virus (anti-HCV) among
      health care workers was 2.9%. We observed a hepatitis C attack rate of 11.5% per
      year in the anti-HCV-negative hemodialysis patient population. An average of 9.4%
      of the hemodialysis patients were chronic carriers of hepatitis B virus (HBV)
      (range 1.8% - 20.4%), while 48.9% showed markers of previous HBV infection. The
      HBV attack rate was 4.5% per year (range 0% - 6%). These results indicate an
      alarming high prevalence of anti-HCV among hemodialysis patients of this studied
      region.

PMID- 7569639
TI  - Paracoccidioides brasiliensis. A mycologic and immunochemical study of a sample
      isolated from an armadillo (Dasipus novencinctus).
AB  - A sample of P. brasiliensis isolated from the spleen and the liver of an
      armadillo (Dasipus novencinctus) has been analysed under a mycological and
      immunochemical viewpoint. The armadillo was captured in an area of Tucurui (State
      of Para, Brazil), the animal being already established as an enzootic reservoir
      of P. brasiliensis at that region of the country. This sample maintained in the
      fungal collection of the Tropical Medicine Institute of Sao Paulo (Brazil)
      numbered 135, has got all the characteristics of P. brasiliensis, with a strong
      antigenic power and low virulence for guinea-pigs and Wistar rats. The specific
      exoantigen of P. brasiliensis--the glycoprotein with a molecular weight of 43 kDa
      -was easily demonstrated with double immunodiffusion, immunoelectrophoresis, SDS
      PAGE and immunobloting techniques.

PMID- 7569648
TI  - FAPESP--sponsored research.

PMID- 7569649
TI  - Note on sandflies associated with a tegumentary leishmaniasis focus in Salta,
      Argentina, 1988.

PMID- 7569647
TI  - Characterization of a Trypanosoma cruzi strain isolated from a non-endemic area
      in northeast Brazil.

PMID- 7569650
TI  - Diagnostic imaging of fungal sinusitis: eleven new cases and literature review.
AB  - Fungal sinusitis should always be considered in the differential diagnosis of
      chronic or recurring sinusitis resistant to adequate medical treatment. A high
      index of suspicion is necessary for the diagnosis, and the clinical examination
      is rarely conclusive. The definitive diagnosis depends on the pathologist in most
      cases. We reviewed retrospectively the imaging findings, specifically computed
      tomography (CT) and magnetic resonance (MR), in a series of fungal sinusitis
      patients. Non-enhanced CT scan is more sensitive than conventional X-ray in
      detecting the classical focal areas of hyper-attenuation and calcification seen
      in soft-tissue masses of fungal sinusitis. MR findings of hypo-intense signals on
      T1-weighted sequences which progress to signal-void area on T2-weighted
      sequences, are characteristic features of fungal sinusitis; however, it is
      reserved for cases where intracranial invasion is suspected or CT findings are
      inconclusive.

PMID- 7569646
TI  - Clinical-epidemiologic study of schistosomiasis mansoni in Ponte do Pasmado, a
      village in the municipality of Itinga, state of Minas Gerais, Brazil, 1992.
AB  - A clinical-epidemiologic study of schistosomiasis mansoni was conducted in the
      population of Ponte do Pasmado, a village in the municipality of Itinga, state of
      Minas Gerais, Brazil. Faecal parasitology by the Kato-Katz method and clinical
      examination were performed in 93.8% and 82.8% of the local population,
      respectively. A socioeconomic survey was also made and the signs and symptoms
      presented by the patients were recorded, as well as their contacts with natural
      waters. The rate of Schistosoma mansoni infection was 50.3%; the peak of
      infection occurred during the second decade of life; there was a predominance of
      low egg counts in faeces (85.89% of positive patients eliminated less than 500
      eggs per gram of faeces); the splenomegaly rate was 1.23%. When the risk factors
      for S. mansoni infection were studied, significant risks were detected in
      activities such as fetching water, washing dishes, bathing, and crossing streams.

PMID- 7569651
TI  - Mediastinal emphysema associated with functional endoscopic sinus surgery. A case
      report.
AB  - A case of mediastinal emphysema after functional endoscopic sinus surgery (FESS)
      is presented. Mediastinal emphysema is a rare and previously unreported
      complication after FESS. The possible aetiologies are discussed.

PMID- 7569652
TI  - Successful treatment of ozena with ciprofloxacin.
AB  - Rhinitis chronica foetida, or ozena, is a rare chronic inflammatory disease. The
      aetiology and pathogenesis are still not satisfactory explained. For many years
      various medical and surgical methods for the treatment of this slowly progressive
      and disabling disease have been tried without permanent success so far. The new
      fluoroquinolones with excellent effect on gram-negative bacteria and high
      suitability for oral use offer a potentially attractive treatment for ozena. We
      review our experience in the treatment of 10 patients with ciprofloxacin in a
      daily dose of 500-750 mg b.i.d. for 1-3 months. The patients have been followed
      regularly for up to 26-74 months after treatment and in all of them we registered
      permanent disappearance of odour, crusting, and growth of Klebsiella ozenae. We
      conclude that ciprofloxacin provides a step towards better conservative therapy
      for patients with ozena.

PMID- 7569653
TI  - Prevalence study of nasal septal deformities in Korea: results of a nation-wide
      survey.
AB  - A nation-wide survey investigating the prevalence and risks of nasal septal
      deformity (NSD) was conducted by a group of otolaryngologists from July through
      October 1991. The total number of subjects surveyed was 9,284, and these were
      drawn from 2,899 households residing in 60 different areas throughout the
      country. The overall prevalence of NSD was 22.38%, and NSD tended to predominate
      in males and to increase with age. According to Mladina's classification, the
      most common type was type 1, followed by types 2, 3, 5, 7, 4, and 6. A positive
      correlation between nasal trauma history (NTH) and NSD was statistically
      confirmed (p < 0.01).

PMID- 7569654
TI  - Cell suspension cultures and adenoid epithelium: an assessment of the source of
      material for human ciliary function experiments in vitro.
AB  - The aim of this study was to explore the usefulness of two different in vitro
      models for studying the function of human upper respiratory cilia, i.e. cell
      suspension cultures of human upper airway epithelium, and ciliated adenoid
      epithelium. Ciliary beat frequency (CBF) and signal consistency (SC), as
      parameters of ciliary function, were measured by a computerized photo-electrical
      method. Measurements after one week revealed that CBF of ciliated aggregates from
      cell suspension cultures had deteriorated to a mean of 5.8 Hz. In the subsequent
      period, it remained at this rather low and non-physiological level. SC decreased
      too, although not as dramatically. These results indicate that ciliated
      aggregates from cell suspension cultures cannot be used for human ciliary
      function experiments in vitro. On the other hand, in ciliated adenoid epithelium,
      CBF remained constant for a period of 5 h, although SC decreased after 30 min.
      Because of this result and the fact that ciliated adenoid epithelium is easily
      obtainable, we regard this material as suitable for studying human ciliary beat
      in vitro.

PMID- 7569656
TI  - Study of nasal cytology in atopic patients after nasal allergen challenge.
AB  - In order to study the normal and pathological inflammatory cell population in
      nasal secretions, nasal microsuction has been performed in 18 atopic patients and
      10 healthy volunteers after nasal allergen and/or PBS challenge. After cytospin,
      the samples have been stained with May-Grunwald-Giemsa solution. Three hundred
      inflammatory cells have been counted by light microscopy, and the percentage of
      each cell type has been calculated. Results show that only a significant increase
      (p < 0.01) in the percentage of eosinophils 1-10 h after nasal allergen challenge
      occurs. In general, this finding correlates well with the symptom of nasal
      obstruction as measured by passive anterior rhinomanometry (PAR) during the late
      phase, but not with the number of sneezes. In agreement with the literature, late
      phase nasal obstruction is shown to be accompanied by an increase in the
      percentage of eosinophils in nasal secretions. The potential role of eosinophils
      in the pathogenesis of the late phase in the inflammatory events after nasal
      allergen challenge has again been confirmed by our study. This study further
      confirms the usefulness of nasal microsuction as a sampling technique, providing
      uniform and adequate nasal cytological specimen for the analysis of nasal
      cytology.

PMID- 7569655
TI  - Electron microscopical studies of the cell population in nasal secretions.
AB  - The purpose of this study is to identify the cell types and ultrastructural
      changes of the cells in nasal secretions, and to understand the pathology of
      allergic and infectious rhinitis. Nasal secretions from 20 patients with allergic
      rhinitis and 15 patients with infectious rhinitis have been observed by
      transmission electron microscopy. The cell population of the allergic group
      consists of (in order of predominance): epithelial cells, eosinophils,
      neutrophils, lymphocytes, basophilic cells (basophil leukocytes and mast cells),
      and macrophages. In the infectious group the population contains: neutrophils,
      epithelial cells, macrophages, and lymphocytes. Marked degranulation has been
      observed in the granules of eosinophils in allergic nasal secretions together
      with granule fusion, vacuolation, and signs of phagocytosis. Increased numbers of
      basophil leukocytes and mast cells are also a feature of the allergic nasal
      secretion. Degranulation of neutrophils is markedly increased in the infectious
      group as compared to the allergic group. Clustered epithelial cells are observed
      in the allergic group more often than in the infectious group. Four types of
      lymphocytes with different morphological features are observed in both groups,
      i.e. small lymphocyte, T-lymphocyte-like cells, large granular lymphocyte-like
      cells, and plasma cells. The results of the present study show special
      ultrastructural characteristics in the cell population of allergic nasal
      secretions, i.e., an increase in the number of degranulated eosinophils and
      basophilic cells, clustered epithelial cells, and large granular lymphocytes,
      while an increase in degranulated neutrophils and macrophages with marked
      phagocytosis are characteristic for infectious nasal secretions.

PMID- 7569658
TI  - The mask: style and volume do not influence rhinomanometry.
AB  - We have tested the influence of face-mask style and volume on rhinomanometric
      measurements. Using an artificial head-and-piston pump to standardize the test
      conditions, four types of face masks (volumes varying from 120 to 200 ml) have
      been tested in a series of 20 measurements per mask. No statistical difference
      could be found between the series using a Chi-square test. We conclude that there
      is no influence of form and volume of the face mask on the accuracy of the
      rhinomanometric measurement.

PMID- 7569657
TI  - Nasal resistance in recumbency and sleep.
AB  - Nasal resistances to respiratory airflow were measured by computer-assisted
      rhinomanometry in 21 adult males without major clinical nasal pathology.
      Measurements were obtained when seated and repeated on assumption of recumbency
      and during sleep. Resistance in Pa/cm3/s of subjects (n = 21) increased from a
      mean (+/- SD) of 0.14 +/- 0.07 in seated posture to 0.35 +/- 0.32 in recumbency.
      In the majority of subjects the increase was modest and was unaffected by sleep.
      It is suggested that unrecognized mucosal abnormality with resulting impairment
      of vascular tone or minor structural deviation of the nasal septum could account
      for the few cases of marked elevation of nasal resistance we observed in
      recumbency.

PMID- 7569659
TI  - Manometric rhinometry: a new method of measuring nasal volume.
AB  - A new method of measuring the volume of the air space in the nose and sinuses is
      presented. We have called this method "manometric rhinometry." By closing off the
      nose anteriorly and posteriorly a closed space is created. A volume of air is
      then removed and the resultant pressure change is recorded. The original volume
      is calculated from the pressure change. Twenty adults have been investigated
      using this method. The volume recorded ranged from 78 to 198 ml (average: 138
      ml). Test-retest analysis showed a correlation coefficient of 0.98. In addition,
      24 children aged 4 to 12 years were examined. Their volumes were 43 to 198 ml.
      Test-retest analysis gave a correlation coefficient of 0.94. The significance of
      these findings is discussed.

PMID- 7569660
TI  - Endoscopic sinus surgery in sinusitis.
AB  - In terms of functional treatment of sinonasal pathologies, endoscopic surgery
      represents a spectacular advance, offering excellent illumination, views of areas
      previously impossible to monitor, and the ability to view the main reference
      points in the surgical field. Over a five-year period (1988-1993), the authors
      have performed 278 paranasal sinus operations, using endoscopic techniques. The
      results obtained in 250 patients, with a minimum follow-up period of one year,
      have been analyzed. The criteria of assessment used include: self-assessment by
      the patient and the surgeon's assessment, made on basis of the endoscopic data.
      The best results were obtained in cases of antrochoanal polyps, polyposis not
      associated with asthma or acetylsalicylic acid (ASA) sensitivity, circumscribed
      chronic sinusitis, and aspergillomas. The worst results, with a high rate of
      recurrence, have been obtained with ASA sensitivity and chronic suppurative pan
      sinusitis. It is essential to reach a consensus on the staging of polyposis so
      that treatment can be monitored adequately, even though, in itself, the pathology
      is difficult to classify as it can vary in a single patient for no apparent
      reason. On the other hand, there is a difference between the subjective and
      objective assessment of the condition, and this makes it even harder to explain
      the results obtained.

PMID- 7569661
TI  - The place of endonasal endoscopy in the treatment of orbital cellulitis.
AB  - Orbital cellulitis secondary to acute sinusitis is uncommon, dangerous, and can
      lead to blindness and death. The ethmoid is the predominantly involved sinus.
      Management policy consists of early drainage of the affected sinus combined with
      systemic antibiotic therapy. If no improvement is achieved within the first 48 h,
      exploration of the fronto-ethmoidal region is mandatory. Endonasal endoscopic
      surgery facilitates early drainage of the affected sinus, eradication of the
      disease from the fronto-ethmoidal region, and drainage of the subperiosteal
      abscess. Sixteen cases of orbital cellulitis were treated successfully by
      endonasal endoscopic surgery with no complications.

PMID- 7569662
TI  - The endoscopic endonasal surgical technique in the treatment of chronic recurring
      sinusitis in children.
AB  - Chronic recurring sinusitis (CRS) is a difficult diagnosis to make in the
      paediatric patient. However, increased awareness by physicians and improved
      technology are contributing to an increasing frequency of this diagnosis.
      Children with their immature development of the paranasal sinuses and
      immunological systems present special problems in the treatment of CRS. Concern
      must be given to potential alteration of the development of the paranasal sinus
      system and tooth buds in the maxilla by a surgical procedure in children. Various
      surgical procedures have been recommended in the past in the treatment of CRS
      failing medical management. A review of 124 paediatric patients undergoing
      endoscopic endonasal sinus surgery using the technique of Messerklinger and
      Stammberger in the treatment of CRS over an 11-year period is presented. A
      detailed questionnaire regarding patient's satisfaction and symptomatic relief
      has been sent to all patients. The results indicate a successful outcome from
      this technique and a high level of patient satisfaction. No complications such as
      CSF leak or orbital injury have been encountered, and no evidence of altered
      facial growth and development has been noted. We find the endoscopic endonasal
      technique to be a safe and effective method in the treatment of children with CRS
      failing medical management.

PMID- 7569663
TI  - An introduction to drug disposition: the basic principles of absorption,
      distribution, metabolism, and excretion.
AB  - A knowledge of the fate of a drug, its disposition (absorption, distribution,
      metabolism, and excretion, known by the acronym ADME) and pharmacokinetics (the
      mathematical description of the rates of these processes and of concentration
      time relationships), plays a central role throughout pharmaceutical research and
      development. These studies aid in the discovery and selection of new chemical
      entities, support safety assessment, and are critical in defining conditions for
      safe and effective use in patients. ADME studies provide the only basis for
      critical judgments from situations where the behavior of the drug is understood
      to those where it is unknown: this is most important in bridging from animal
      studies to the human situation. This presentation is intended to provide an
      introductory overview of the life cycle of a drug in the animal body and
      indicates the significance of such information for a full understanding of
      mechanisms of action and toxicity.

PMID- 7569664
TI  - Basic principles of pharmacokinetics.
AB  - Pharmacokinetics may be defined as what the body does to a drug. It deals with
      the absorption, distribution, and elimination of drugs but also has utility in
      evaluating the time course of environmental (exogenous) toxicologic agents as
      well as endogenous compounds. An understanding of 4 fundamental pharmacokinetic
      parameters will give the toxicologic pathologist a strong basis from which to
      appreciate how pharmacokinetics may be useful. These parameters are clearance,
      volume of distribution, half-life, and bioavailability.

PMID- 7569665
TI  - The role of drug metabolism in drug discovery: a case study in the selection of
      an oxytocin receptor antagonist for development.
AB  - Drug discovery is a process involving multiple disciplines and interests. During
      the research phase of drug discovery, usually a large number of compounds are
      evaluated for biological activity and toxicological potential in animal species.
      Various types of problems with respect to pharmacodynamics, pharmacokinetics, and
      toxicity are commonly encountered at this stage. Drug metabolism, as a discipline
      participating in a drug discovery team, can play an important role in identifying
      factors underlying the problems, facilitate the optimal selection of compounds
      for further development, provide information on metabolites for possible
      improvement in drug design, and contribute to the identification of the
      appropriate animal species for subsequent toxicity testing. During the process of
      evaluating oxytocin receptor antagonists for further development for treatment of
      preterm labor, in vivo and in vitro drug metabolism studies conducted in rats,
      dogs, and monkeys contributed to the selection of L-368,899 as the development
      candidate on the basis of pharmacokinetic and metabolism observations. The
      presence of active N-demethylated metabolites of two other equipotent compounds
      in rats and dogs was found to be the major factor responsible for the discrepancy
      between oral bioavailability and efficacies observed for these 2 compounds. For L
      368,899, a compound that demonstrated 20-40% oral bioavailability in rats, dogs,
      and chimpanzees, extensive first-pass metabolism rather than absorption was
      determined as the major factor responsible for the poor bioavailability (< 1%) in
      rhesus monkeys. In vitro metabolism studies with hepatic microsomes from rats,
      dogs, monkeys, and humans substantiated the conclusion that the rate of hepatic
      metabolism of L-368,899 in monkeys is faster than in the other species.

PMID- 7569666
TI  - Goals, design, timing, and future opportunities for nonclinical drug metabolism
      studies.
AB  - The nonclinical ADME (adsorption, distribution, metabolism, and excretion)
      studies employed during drug development are dependent on the regulatory
      expectations and the changing development focus from nonclinical to clinical
      issues. These evolving issues necessitate that the development goals for ADME
      studies also change during the development process. The rationale for these goal
      changes and their impact on the timing and design of the ADME studies are
      discussed in the context of drug development at Glaxo Inc. The progress in the
      technology and knowledge in drug metabolism and in biology provide new
      opportunities for pharmaceutical companies in predicting drug toxicities relevant
      to humans. Two case examples are discussed to illustrate this opportunity.

PMID- 7569668
TI  - Differences between pharmacokinetics and toxicokinetics.
AB  - Pharmacokinetics has evolved into a highly interactive discipline in which the
      dispositional characteristics of an administered drug are often compared to the
      time course of observed drug effects. The more recent discipline of
      toxicokinetics is undergoing a similar, although belated, evolution. While
      toxicokinetic studies were first intended to demonstrate merely that toxicology
      test animals received drug, they now provide a critical evaluation of drug
      disposition at toxicologic doses and also the relationships between toxicokinetic
      values and the occurrence and time course of toxic events. Different dose levels
      used in toxicokinetics, compared to pharmacokinetics, give rise to technological
      changes in such factors as solubility, stability, absorption, presystemic
      clearance, protein binding, and metabolism that may be influenced by dose size,
      and may give rise to profound differences in the design and interpretation of
      studies. Pharmacokinetic and toxicokinetic studies also have different
      objectives. While preclinical pharmacokinetic and pharmacodynamic studies provide
      correlates, based on generally well-established parameters, that may provide
      useful but perhaps not essential information to guide drug dosage in man,
      information from toxicokinetics and toxicodynamic studies, which is difficult to
      obtain because of capricious interspecies differences in dispositional
      characteristics and organ/tissue sensitivities, is critical to predict the
      behavior and safety of compounds in man.

PMID- 7569667
TI  - Relationship of DNA adducts derived from 2-acetylaminofluorene to cell
      proliferation and the induction of rodent liver and bladder tumors.
AB  - Pharmacokinetic models have been developed to assist in extrapolating results
      from rodent bioassays. However, in numerous circumstances, it is necessary to
      combine such models with cellular response models to fully define interspecies
      and dose extrapolations. Interactions between pharmacokinetic target tissue end
      points (DNA adduct formation) and cellular proliferation in liver and urinary
      bladder carcinogenesis is illustrated with the results from the ED01 study
      involving 2-acetylaminofluorene administered to female mice. The interaction of
      genotoxic and cell proliferative effects are also illustrated in a co
      carcinogenesis study with low doses of N-[4-(5-nitro-2-furyl)-2
      thiazolyl]formamide and high doses of sodium saccharin. The application of such
      interactions to humans is illustrated for the case of cigarette smoke-induced
      bladder cancer.

PMID- 7569669
TI  - Considerations in the design of toxicokinetic programs.
AB  - The objectives of toxicokinetic (TK) studies are to evaluate systemic exposure of
      the toxicity species to drug and/or metabolite(s) and to relate exposure to dose
      level and toxicological findings. The tacit assumption is that such exposure can
      be related to target organ toxicity. Planning a TK program involves early
      development (often during discovery support) of an appropriate plasma assay,
      assurance that the studies conform to Good Laboratory Practices, evaluating
      exposure at steady state, and effective collaboration among toxicologists,
      kineticists, and other relevant disciplines. The 3 types of TK studies-
      prospective, concomitant, and retrospective--each have different goals. The
      various stages of TK program implementation range from those during drug
      discovery and selection to support of chronic toxicity studies. Exposure is best
      expressed as the area under the plasma concentration/time curve of drug and/or
      metabolite(s) and, for highly protein bound drugs, is based on the unbound
      fraction. Although the objectives of TK programs are generally standard and the
      Second International Conference on Harmonization has developed TK guidelines, the
      programs differ among pharmaceutical companies. Some variables in program design
      and implementation include properties of the drug, formulation used,
      characteristics of the target species, ability to develop a toxicokinetic
      toxicodynamic relationship, strategies based on
      scientific/technical/philosophical considerations, dedicated resources, corporate
      support, and effectiveness of interdepartmental collaborations.

PMID- 7569670
TI  - Toxicokinetics/toxicodynamic correlations: goals, methods, and limitations.
AB  - Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug
      exposure in animals and for ensuring that drug exposure is substantially greater
      in animals than that expected in humans at therapeutic doses. The usefulness of
      TK studies can be further enhanced by correlating TK parameters with relevant
      toxicologic end points. The so-called TK/toxicodynamic (TD) correlations can be
      extremely useful in bridging data from studies both within and across species and
      in designing early Phase I clinical trials. These correlations assume that
      toxicologic responses are comparable among species at comparable plasma
      concentrations. This assumption may apply for certain drugs but not for others.
      Therefore, TK/TD correlations should be developed and utilized on a case-by-case
      basis. Such correlations have proven to be extremely useful with anticancer drugs
      in formulating dose escalation strategies in cancer patients to rapidly attain
      the maximum tolerated and/or effective dose. However, these correlations have not
      been utilized effectively in other therapeutic areas. The development of TK/TD
      correlations, their scope, and limitations are discussed in this paper.

PMID- 7569671
TI  - Absorption, metabolism, and other factors that influence drug exposure in
      toxicology studies.
AB  - Drug exposure in toxicology studies is dependent on input from the drug delivery
      system and elimination of the drug once absorbed. Although seemingly
      straightforward, absorption, metabolism, and other factors require a more complex
      interpretation of plasma concentrations and the resulting area under the plasma
      concentration versus time curve values at doses free from significant toxicity.
      Absorption may be saturable due to the intestinal, physiologic processes
      necessary for drug transfer, or intrinsic drug solubility limits may lead to a
      plateau in systemic plasma concentrations. Different vehicles or administration
      of drug with food or in the diet may be investigated in an effort to improve
      systemic exposure. Metabolic profiles may be examined to aid in the selection of
      a toxicology species more metabolically similar to humans. This will assist in
      providing adequate safety margins for metabolites as well as parent compound in
      comparison to humans. Safety assessment of drug metabolites has taken on added
      significance as our knowledge of metabolite pharmacokinetics in humans has
      increased. Correlation of free drug concentrations, determined in protein binding
      studies, may provide a better correlation with toxic effects than do total drug
      concentrations. Other factors, such as age, gender, and dosing interval need to
      be considered when interpreting toxicology studies.

PMID- 7569672
TI  - Concomitant toxicokinetics: techniques for and interpretation of exposure data
      obtained during the conduct of toxicology studies.
AB  - Toxicokinetic analyses have become a routine component of preclinical toxicology
      studies with pharmaceutical candidates. Evaluation of plasma and/or tissue
      samples from animals used in toxicology studies (or concurrent satellite groups)
      provides information on dose proportionality, the potential for dose
      accumulation, and the sex and species differences in distribution and
      elimination. Toxicokinetic information is used by toxicologists, toxicology
      management, clinicians, institutional review boards, regulatory agencies to
      ensure that exposure has occurred in animal species to a sufficient extent to
      minimize the potential risk of toxicities in humans. The requirements for
      descriptive toxicokinetics change depending on the stage of development of new
      drug candidates. Early in development, documentation of exposure in 1 species and
      sex of laboratory animal might be enough to justify preliminary development costs
      and initiation of product development. Later in development, it becomes necessary
      to know how new drug candidates are distributed and eliminated following
      subchronic and chronic administration in multiple species and both sexes.
      Finally, knowledge of toxicokinetics is used to help establish doses in long-term
      oncogenicity studies. Scientific, public, and regulatory pressures have recently
      dictated that the number of animals used in toxicology studies be closely
      monitored and minimized. Toxicokinetic evaluation of new drug candidates by a
      staggered sampling design is now routinely performed in our laboratories to
      maximize information obtained while reducing animal use.

PMID- 7569673
TI  - Ancillary approaches to toxicokinetic evaluations.
AB  - The principal objective of toxicokinetic studies is to assess systemic exposure
      of the toxicity species to test compound during nonclinical toxicity studies by
      generation of pharmacokinetic data on the rate, extent, and duration of exposure.
      Toxicokinetics are normally integrated within the toxicity studies (concomitant);
      however, there are a number of circumstances when prospective, retrospective, or
      other ancillary types of toxicokinetic studies are performed in support of
      toxicity studies. The need for retrospective toxicokinetic studies arises when
      the original toxicity study was conducted with insufficient plasma concentration
      determinations, especially when pilot toxicity studies show lack of toxicity or
      unusual organ toxicities. Examples of ancillary toxicokinetic studies from the
      Drug Metabolism and Drug Safety departments at The R. W. Johnson Pharmaceutical
      Research Institute and from the scientific literature are provided that highlight
      the challenges associated with these alternate approaches. Each example includes
      a discussion of the rationale for the supportive toxicokinetic study, the
      specific experimental designs, the data interpretation, and the usefulness of the
      toxicokinetic data in decision-making. The ancillary toxicokinetic studies cited
      provided important information on establishing systemic exposure during long-term
      toxicity studies, allowing comparisons to human exposures, elucidating compound
      related toxicities, and explaining lack of toxicity due to autoinduction and
      resulting low levels of parent compound.

PMID- 7569674
TI  - Expression of exposure in negative carcinogenicity studies: dose/body weight,
      dose/body surface area, or plasma concentrations?
AB  - Evaluation of positive findings in a rodent carcinogenicity study and the
      subsequent extrapolation to humans is based on chemical structure, mutagenicity,
      pharmacology, hormone changes, chronic toxicity, and the nature of the tumors
      induced. For negative studies, adequacy of exposure may become an issue. The use
      of plasma concentrations as a metric for exposure assumes that each species
      responds in a similar manner to a given concentration; data are now available
      that demonstrate that this is not generally true for carcinogenicity. The use of
      the body surface area metric (i.e., mg/m2) is a special case of interspecies
      allometric scaling (i.e., W0.67). For a chemical to be amenable to such scaling
      in toxicology, it must satisfy 3 criteria: (a) the concentration-time profile of
      the putative toxicant at the site of action must be governed by a scalable
      pharmacokinetic process (e.g., glomerular filtration); (b) the mechanism of
      action and the susceptibility of each species to a given systemic exposure must
      be the same and, for example, be independent of lifespan, cellular repair
      mechanism/rate, and so forth; and (c) the biological response must depend only on
      size (e.g., not on race, strain, gender, age, or parity). Carcinogens rarely, if
      ever, meet these criteria. An empirical analysis of carcinogenic potency data in
      rodents and in humans shows that, in general, exposure is best expressed in terms
      of mg/kg body weight.

PMID- 7569676
TI  - Preclinical drug metabolism programs for food-producing animals.
AB  - To register a new veterinary drug for use in food-producing animals, the sponsor
      must demonstrate that drug-related residues in the edible tissues (liver,
      kidneys, muscle, fat, and milk or eggs) of treated animals are safe when consumed
      by humans. The sponsor must develop information on the amount, persistence, and
      chemical nature of the drug-derived residue in the edible tissues in order to
      ensure safety. This information is compared to that on the metabolism and
      toxicity of the compound in the laboratory animal species used for the toxicity
      evaluation. The toxicity data is utilized to establish the safe concentration of
      drug-related residue in the edible tissues. An estimate of the safe concentration
      is necessary to proceed with residue studies that will adequately determine the
      rate of depletion of total residue over the projected range of probable safe
      concentrations. Appropriate study design requires close communication among the
      toxicologist, pathologist, and residue chemist. The safe concentration of total
      residue and residue depletion profile are used to determine the withdrawal period
      for the veterinary product. The required studies, including design and timing,
      will be discussed.

PMID- 7569679
TI  - Peer review in toxicologic pathology.
AB  - Peer review of histopathology findings in safety assessment studies involving
      rodents and other animals is a relatively recent procedure in toxicologic
      pathology. It serves to ensure the integrity of the pathology evaluation in
      safety studies, encourages consistency of diagnostic criteria and use of common
      terminology, and provides a method of continuing education for participants. The
      use of a standardized system of pathology nomenclature and diagnostic criteria,
      such as the Society of Toxicologic Pathologist's Guides for Toxicologic
      Pathology, is of great value in the procedure. Pathology reviews may involve
      government-sponsored bioassay programs, in-house industrial corporations, or
      individual peer reviews suggested or required by government regulatory agencies.
      Pathology Working Groups can be an integral part of the review process. The
      extent of the peer review is primarily dependent on the study results; however,
      other variables such as confidence of the data, study size and duration,
      complexity, and purpose are also important considerations. Essential components
      of any peer review, however, include selection of tissues/lesions for review, by
      a reviewing pathologist, discrepancy resolution, data modification, and
      documentation of all aspects of the review process. Specific procedures for
      pathology peer review are discussed. Disagreements among pathologists discovered
      in peer reviews can be resolved by several methods and examples will be
      presented. The entire pathology peer review process should be a learning
      experience for all involved and can help ensure the integrity of animal
      toxicology studies used for important regulatory decisions involving the use of
      chemicals in our society.

PMID- 7569677
TI  - Toxicokinetic challenges in the pharmaceutical industry.

PMID- 7569675
TI  - The use of in vitro metabolism techniques in the planning and interpretation of
      drug safety studies.
AB  - An important issue in toxicology is the suitability of the data obtained with
      experimental animals for human risk assessment. Because it is not possible to use
      humans in long-term toxicological studies, the use of animals will continue.
      However, the data obtained in animal studies can be better extrapolated to the
      patient by utilizing bridging studies with in vitro models of human drug
      metabolism. There are 2 basic categories of in vitro methods for the examination
      of human liver drug metabolism. The first group of in vitro methods consists of
      the cellular models, which include primary hepatocytes, liver slices, and cell
      lines. The second group is the use of preparations of the drug-metabolizing
      enzymes such as tissue homogenates, subcellular fractions, and isolated enzymes.
      Studies modeling both the human and experimental animal metabolism of a drug are
      useful in the design of toxicological studies. In vitro studies can identify
      metabolites, species-specific metabolic routes, and the experimental animal model
      that best reflects the potential human exposure to the drug and its metabolites.
      This information can also be useful in the design of the clinical studies by
      identifying human metabolites, the enzymes responsible for the metabolic
      clearance of the drug, the effects of genetics and other host factors on the
      metabolism of the drug, and potential drug-drug interactions. An example of how
      such information is generated and interpreted is presented.

PMID- 7569680
TI  - Role of Drug Metabolism and Pharmacokinetics in Toxicologic Pathology.
      Proceedings of the 13th International Symposium of the Society of Toxicologic
      Pathologists. Charleston, South Carolina, June 5-9, 1994.

PMID- 7569681
TI  - Cytokeratin fragment 21-1 in gynecologic malignancy: comparison with cancer
      antigen 125 and squamous cell carcinoma-related antigen.
AB  - We measured serum cytokeratin fragment 21-1 (CYFRA 21-1) levels by a solid-phase
      immunoradiometric assay in 102 healthy Japanese women, and set the reference
      value at 1.9 ng/ml (mean +2 SD of the serum levels based on a linear
      distribution). Pretreatment serum CYFRA 21-1 levels were also analyzed in 235
      women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were
      compared with the serum levels of CA 125 and SCC. The respective positivity rates
      for CYFRA 21-1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they
      were 4.2 and 30.8% in benign ovarian masses. CYFRA 21-1 had an accuracy of 61.3%
      in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%).
      The positive predictive value of CYFRA 21-1 for ovarian malignancy reached 94.1%,
      which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These
      findings indicate the potential usefulness of CYFRA 21-1 as a tumor marker for
      ovarian malignancy. In addition, the positivity rates fo CYFRA 21-1 in cervical
      cancer (51.2%) and endometrial cancer (52.2%) were also similar to the respective
      rates for SCC and CA 125, which suggests that CYFRA 21-1 seems to be a general
      tumor marker for gynecologic malignancy.

PMID- 7569678
TI  - Food and Drug Administration viewpoints on toxicokinetics: the view from review.
AB  - The importance of drug kinetics for interpretation of toxicity findings and for
      cross-species toxicity assessment has been long recognized. Recently, an
      international effort was initiated to standardize guidance on the kinetic data to
      be collected in conjunction with toxicity studies. The guidance addresses the
      kinetic data to be included in studies on carcinogenicity, reproduction toxicity,
      genotoxicity, and single- and repeat-dose toxicity. In various stages of
      development or implementation, the guidance is intentionally nondetailed
      regarding the specific kinetic assessments to be performed. This is to allow
      flexibility in study design and ensures that scientific judgment is used to
      determine the appropriate kinetic endpoints to achieve study- and drug-specific
      goals. Some examples of how kinetics have been used at the Food and Drug
      Administration in review of toxicity studies submitted in drug applications are
      presented. The examples discussed demonstrate successful and unsuccessful
      integration of kinetics into study design and interpretation and highlight the
      impact on the drug development program from a regulatory perspective.

PMID- 7569682
TI  - Effects of gonadal steroids on the growth of human pituitary adenomas in vitro.
AB  - The effects of testosterone (T), dihydrotestosterone (DHT) and methyltrienolone
      (R 1881) on cell proliferation of eight human pituitary tumors in culture wre
      assessed by [3H]thymidine incorporation and compared to those of progesterone
      (Pg) and 17 beta-estradiol. Receptors for androgens (AR), estrogens (ER) and
      progesterone (PgR) were characterized. AR had a significant inhibitory effect on
      all AR-positive tumors, whatever their hormonal content. Inhibitory effects of
      either T and DHT < R1881 < Pg were observed in tumors co-expressing AR and PgR.
      The inhibitory effect of R 1881 on a PgR-positive/AR-negative tumor suggested
      that R 1881 action was partially PgR-mediated. The effects of either T or the
      nonaromatizable DHT and R 1881 were unrelated to ER expression. We conclude that
      AR can modulate the growth of human pituitary tumors through direct receptor
      mediated intracellular pathways which may be common to various pituitary cell
      types.

PMID- 7569683
TI  - The prognostic significance of immune changes in patients with renal cancer and
      melanoma treated with interferon-alpha 2b.
AB  - We evaluated the response rate and the immunorestorative properties of
      subcutaneously administered interferon-alpha 2b (IFN-alpha 2b) in patients with
      advanced renal cell carcinoma (RCC) and melanoma (MEL) and correlated the immune
      status with clinical responses. Thirty-five patients with advanced RCC and 12
      with MEL were treated with recombinant IFN-alpha 2b. The dose was increased
      progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week
      and thereafter 15 x 10(6) IU subcutaneously. The response rate for RCC patients
      was as follows: (1) 6 patients achieved partial responses; (2) 9 patients had
      stable disease, and (3) 20 patients progressed. The response rate for patients
      with MEL was as follows: (1) 4 patients experienced partial response and (2) 8
      patients progressed. In all patients blood was withdrawn prior to IFN treatment
      and then monthly. T lymphocytes after isolation from peripheral blood were tested
      for proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and
      allogeneic mixed lymphocyte reaction (allo-MLR), interleukin-2 production (IL
      2prod), expression of IL-2 receptors (IL-2rec) during the allo-MLR, and
      interleukin-1 production (IL-1prod) by peripheral blood monocytes. Striking
      increases were demonstrated in all parameters 1 month after treatment with IFN
      alpha 2b. Patients with RCC experiencing a partial response showed a mean
      increase of 50% in the auto-MLR, 95% in the allo-MLR, 62% IL-2prod, 88% IL-2rec
      and 76% in IL-1prod.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569684
TI  - Influence of human luteinizing hormone on cell growth and CA 125 secretion of
      primary epithelial ovarian carcinomas in vitro.
AB  - In the present study, the influence of human luteinizing hormone(hLH) on the
      growth and the CA 125 secretion of primary ovarian carcinoma cell cultures
      derived from 11 previously untreated patients was investigated. Two different
      patterns of in vitro growth of unstimulated ovarian carcinoma cells could be
      detected: 5 cell cultures in which no changes of cell number were observed during
      an incubation period of 6 days (group A) and 6 cell cultures which grew without
      any hormonal support (group B). All tumors of group A showed enhanced cell
      proliferation when hLH was added to the culture medium, reaching a maximum at
      dosages of 100 mIU/ml on day 2 after incubation, while such an effect was not
      observed in group B. In most cases, no positive correlation was found between hLH
      induced cell growth and CA 125 release. Our findings demonstrated a dose
      dependent hLH-induced stimulation of epithelial ovarian tumors in vitro.

PMID- 7569685
TI  - Flow cytometric nuclear DNA content analysis of renal tumors in children:
      prognostic significance of nuclear DNA ploidy.
AB  - We studied, by flow cytometry, the DNA contents of paraffin-embedded tumor
      specimens from 90 infants and children with kidney tumors, and analyzed the
      relationship of DNA ploidy with histological types and prognosis. Data of
      adequate quality were obtained from 90 cases: 65 tumors with favorable histology,
      5 congenital mesoblastic nephromas and 20 tumors with unfavorable histology. The
      90 cases had nuclear DNA histogram patterns that were classified as DNA diploid
      in 64 tumors, aneuploid in 19 and tetraploid in 7. There were no significant
      correlations between DNA ploidy and histological types or clinical stages.
      Survival rates for patients with diploidy were 80 and 70% at 2 and 5 years,
      respectively, and those of patients with aneuploidy were 72 and 61% at 2 and 5
      years, respectively. On the other hand, patients with a DNA tetraploid pattern
      had significantly worse survival rates of 43 and 29% at 2 and 5 years,
      respectively. Among patients with aneuploidy or tetraploidy, the S-phase
      fractions in those who died (mean +/- SD: 10.3 +/- 4.1 and 22.1 +/- 11.6%,
      respectively) appear to be greater than those in their surviving counterparts
      (8.8 +/- 4.0 and 12.1 +/- 2.8%). Hence, although the differences between diploid
      and aneuploid DNA patterns were not correlated with differential prognosis in
      children with kidney tumors, a tetraploid pattern clearly indicates a poor
      prognosis, especially in combination with histological types and clinical stages.

PMID- 7569686
TI  - The 1993 ISOBM Abbott Award Lecture. Isozymes, tumor markers and
      oncodevelopmental biology.
AB  - This is the history of discoveries of several enzyme tumor markers in the
      awardees laboratory. The first, beta-glucuronidase, was originally related to the
      physiological actions of estrogens and androgens. Perfection of histochemical
      techniques based on new substrates demonstrated the dual localization of beta
      glucuronidase in endoplasmic reticulum and lysosomes. Tumor tissues, in general,
      are enriched with beta-glucuronidase. Next, acid phosphatase of the prostate
      gland possesses the distinctive property of undergoing inhibition by L-tartrate.
      This organ-specific inhibitor was incorporated into the Fishman-Lerner method for
      measuring serum acid phosphatase of prostatic origin. This significantly
      increased the specificity of the measurement of serum acid phosphatase for
      prostatic cancer. Finally, the discovery of the Regan Isoenzyme, placental
      alkaline phosphatase (PLAP) in a patient with disseminated lung cancer provided a
      tumor marker useful in the management of gonadal tumors, in particular. Closely
      related to PLAP is germ cell alkaline phosphatase which is eutopically expressed
      in seminoma. Finally, radioimmunolocalization and radioimmunotherapy of PLAP in
      these tumors have been achieved by others.

PMID- 7569688
TI  - [Investigation plan for acute kidney failure].
AB  - Acute renal failure often has a complex origin, especially in critically ill
      patient. Moreover, the tools for investigation of renal failure are generally
      unspecific, so that the work-up must be based on several elements. It is
      particularly important to differentiate failure of the kidney itself from
      prerenal or postrenal failure, since the therapeutic implications are very
      different. We propose to base the investigation of acute renal failure on some
      elements to be evaluated in a rapid succession. The complete evaluation should
      also take into account the consequences of renal failure, which also have
      therapeutic implications.

PMID- 7569687
TI  - [Experimental models of acute kidney failure].
AB  - Acute renal failure (ARF) is related to reversible tubular necrosis, usually
      caused by ischemia or toxic substances. Our knowledge of the pathophysiology of
      ARF stems from the study of animal models which reproduce either an ischemic or a
      toxic form of ARF. Classical studies using microdissection and micropuncture have
      characterized the salient mechanisms of ARF: vascular compromise with
      hypoperfusion and decrease in glomerular filtration rate, and tubular insult with
      cell necrosis and high intratubular pressure. More recent studies have emphasized
      the cellular and molecular events occurring during the course of ARF, including
      changes in cytoskeleton and matrix proteins, apoptosis and the role of Heat Shock
      Proteins. Endothelin and growth factors such as epidermal growth factor or
      hepatocyte growth factor seem to be important mediators in the regeneration phase
      of ARF. In various animal models, EGF, HGF or antagonists of endothelin receptors
      have a protective effect on renal function. These findings may be of clinical
      relevance, and suggest future therapeutic approaches in the treatment of ARF.

PMID- 7569690
TI  - [Acute kidney failure induced by drugs or contrast media].
AB  - The incidence of in-hospital acute renal failure (ARF) due to drugs is estimated
      at 20% of all patients hospitalized for ARF. According to recent surveys,
      analgesic and non-steroidal anti-inflammatory drugs are now more frequently
      involved than antibiotics. The incidence of ARF in patients taking angiotensin
      converting enzyme inhibitors is increasing. More than half of the patients have a
      non-oliguric course. Acute tubular necrosis and acute interstitial nephritis are
      found in most biopsied cases. The mortality rate ranges between 6% and 12%. Most
      patients recover but 15% to 20% have some degree of residual renal impairment,
      particularly older and oliguric patients, those with previous chronic renal
      insufficiency and whose ARF period is prolonged. The long-term renal effects of
      NSAIDs is a concern. ARF due to drugs is a preventable disease since two-thirds
      of patients received inappropriately high or prolonged doses of the offending
      drug and or were patients at risk to develop ARF.

PMID- 7569691
TI  - [Acute kidney failure in tubular necrosis].
AB  - Tubular necrosis is the most frequent hospital-acquired cause of acute renal
      failure from renal origin. The two main factors leading to tubular necrosis are
      hemodynamic perturbations and use of nephrotoxic agents. There is recently a
      growing number of reports on tubular necrosis associated with a non traumatic
      rhabdomyolysis. In 60-70% of the cases, more than one contributing factor can be
      identified. In the majority of the patients who developed a transient
      postoperative acute renal failure, co-morbid factors such as diabetes,
      hypertension or major cardiovascular problems, are present. Acute renal failure
      increases the mortality by factors from 2-7. Therefore prevention and (or) early
      correction of the factors leading to tubular necrosis are of great importance.

PMID- 7569689
TI  - [Functional acute kidney failure].
AB  - Prerenal acute renal failure is defined as a reduction in the glomerular
      filtration rate due to a primary disturbance in renal hemodynamics in the absence
      of any structural kidney damage. In case of moderate hypotension or hypovolemia,
      a number of adaptative systemic and intrarenal responses preserve renal perfusion
      and filtration rates, particularly by inducing a marked reduction in
      preglomerular arteriolar resistance and an increase in postglomerular resistance.
      However, these mechanisms are inherently limited. In the presence of advanced
      circulatory failure or iatrogenic pharmacologic interventions compromising these
      renal defense mechanisms, prerenal failure becomes evident. Therefore, prerenal
      failure may occur during acute hemodynamic disturbances due to hypovolemia or
      systemic vasodilatation, in severe cardiac failure, in cirrhosis with ascites,
      and in certain clinical situations following administration of nonsteroidal
      antiinflammatory agents or angiotensin converting enzyme inhibitors. The
      treatment depends on the underlying cause.

PMID- 7569695
TI  - [Hodgkin disease. Diagnosis, clinical course, prognosis, treatment].

PMID- 7569693
TI  - [Contribution of renal biopsy to the diagnosis and treatment of acute kidney
      failure].
AB  - The mortality rate of acute renal failure is still high, about 50%. About 10% of
      the survivors have chronic renal failure, sometimes requiring dialysis. The
      course of some of these cases can be improved by appropriate therapeutic
      measures, if they are undertaken early. Early identification of these lesions is
      therefore mandatory. The clinical diagnosis is often difficult: 1. rare atypical
      forms of acute tubular necrosis, with renal or extrarenal signs, may lead to
      renal biopsy; 2. vascular and glomerular disease are most often recognized
      clinically (sometimes misdiagnosed), but the histological type (and therefore the
      appropriate treatment) cannot be determined; 3. acute interstitial nephritis is
      rarely diagnosed clinically and the nature of the infiltrate remains unknown. In
      certain cases of acute renal failure, the contribution of early renal biopsy to
      the etiological diagnosis and to prognosis and therapy is obvious. In acute renal
      failure, renal biopsy should be considered early in a rather limited number of
      patients (about 20%), everytime the diagnosis of tubular necrosis is doubtful,
      especially in acute renal failure associated with persistent infection, in order
      to guide the therapy.

PMID- 7569694
TI  - [Treatment of acute kidney failure].
AB  - The appropriate treatment of acute renal failure (ARF) is a function of its type
      and of its underlying causes. Functional ARF requires medical treatment directed
      towards the correction of kidney hemodynamic disequilibrium and the restoration
      of adequate glomerular filtration rate (suppression of drugs, correction of
      hypovolemia, hypotension or shock by vascular refilling and inotropic drug
      therapy). Obstructive ARF requires restoration of urinary tract patency by
      urological intervention (internal or external urinary catheter shunt) and
      treatment of factors underlying the obstruction (lithotomy, steroids, radio and
      (or) chemotherapy). Organic ARF commonly necessitates referral to a nephrology
      unit for renal replacement therapy, the choice of treatment modality
      (hemodialysis, hemofiltration, peritoneal dialysis) depending upon availability
      and staff expertise as well as patient clinical condition, associated comorbidity
      and gravity of ARF.

PMID- 7569692
TI  - [Acute kidney failure in glomerulonephritis and in angiitis].
AB  - Some cases of postinfectious glomerulonephritis initially are oligoanuric. Renal
      biopsy is essential to distinguish the purely endocapillary and exsudative form
      from that with endo- and extracapillary proliferation. The former characterises
      spontaneously regressive poststreptococcal glomerulonephritis, which is now rare,
      whilst the latter is caused by various strains of gram-positive and gram-negative
      strains and entails a much less favourable outcome in terms of renal and patient
      survival. Acute renal failure is a common complication of angiitis, mainly
      polyarteris nodosa (PAN) and Wegener granulomatosis. A third variety of
      crescentic glomerulonephritis is due to anti-glomerular basement membrane (GBM)
      antibodies, with or without pulmonary haemorrhage. Glomerular immunofluorescence
      discloses a typical pattern of linear IgG deposits along the GBMs. Treatment
      based on plasma exchanges, corticosteroids and alkylating agents can prevent end
      stage renal failure when undertaken early. Other glomerulopathies may be
      complicated with acute renal failure, including haematuric forms of IgA
      nephropathy.

PMID- 7569697
TI  - [Cancer of the prostate. Diagnosis, clinical course, prognosis, treatment].

PMID- 7569698
TI  - [Torsion of the spermatic cord. Diagnosis, treatment].

PMID- 7569696
TI  - [Proteinuria and (or) hematuria in children. Diagnostic orientation].

PMID- 7569699
TI  - [Depressive syndrome. Diagnostic orientation and treatment].

PMID- 7569701
TI  - [Colonic diverticulosis. Epidemiology, physiopathology, diagnosis, clinical
      course, treatment].

PMID- 7569703
TI  - [Craniomandibular syndrome].

PMID- 7569700
TI  - [Antidepressants. Principles and rules of use].

PMID- 7569702
TI  - [Dysfunctions of the masticatory system].

PMID- 7569706
TI  - [A method of vestibular orientation using digital imaging].

PMID- 7569707
TI  - [The surgical application of vestibular orientation].

PMID- 7569705
TI  - [Geometric principles of the application of the "vestibular" orientation of the
      head].

PMID- 7569704
TI  - [Orthognathic surgery with missing teeth].
AB  - Orthognathic surgery in patients with missing teeth can be divided into two
      categories. In the first case after tooth loss, specially designed bridging is
      required using the prosthesis already in place. In the second case in patients
      with congenital deficiencies, usually sequellae of cleft palate, there is a wider
      range of therapeutic options which are discussed on the basis of observed cases.

PMID- 7569711
TI  - [Customary precautions observed in our everyday practice vis-a-vis HIV as a
      function of our current knowledge].

PMID- 7569709
TI  - [AIDS: current epidemiology, diagnosis and therapy].

PMID- 7569710
TI  - [Maxillofacial manifestations of AIDS].

PMID- 7569712
TI  - [Benign disorders of the oral cavity].

PMID- 7569713
TI  - [Management of erosive lesions of the oral mucosa].

PMID- 7569708
TI  - [Multidisciplinary approach to maxillofacial angiodysplasia].

PMID- 7569714
TI  - [Management of oral aphthae].

PMID- 7569715
TI  - [Allergies to dental prostheses and to amalgam: various data from the
      literature].

PMID- 7569716
TI  - [General ambulatory anesthesia in oral medicine and maxillofacial surgery].

PMID- 7569717
TI  - [The periosteum: the "umbilical cord" of bone. Quantification of the blood supply
      of cortical bone of periosteal origin].
AB  - The Periosteum or periosteal membrane is a continuous composite fibroelastic
      covering membrane of the bone to which it is intimately linked. It consists of
      multipotent mesodermal cells (11, 15). Although the bone cortex is the main
      beneficiary of the principal anatomical and physiological functions of the
      periosteal membrane, the behaviour of the entire bone remains closely influenced
      by the periosteal activity. These principal functions are related to the cortical
      blood supply, osteogenesis, muscle and ligament attachments. Through its elastic
      and contractile nature, it participates in the maintenance of bone shape, and
      plays an important role in metabolic ionic exchange and physiological
      distribution of electro-chemical potential difference across its membranous
      structure. It has also been suggested that the periosteum may have its own
      specific proprioceptive property. This presentation will study the histo-anatomy
      and physiology of the periosteum and will discuss in detail its main functions of
      cortical blood supply and osteogenesis (fig. 1 and 2). It will also present the
      third intermediary report on a current study of the quantification of cortical
      vascularisation of femoral bone via the periosteum, using an isotonic salt
      solution of 85Strontium. The afferent-efferent (arterio-venous) flows of this
      solution in the thigh vascular system of guinea pigs were measured by gamma
      spectrometry after a series of selective macro and micro injections of
      radioactive salt into the femoral arterial system were carried out. Each vascular
      territory was meticulously selected and the injections were made according to
      size, starting with the larger vessels, with or without ligatures of neighbouring
      vessels, going progressively to smaller and smaller vessels not exceeding 100m in
      diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569718
TI  - [Sinus augmentation. Statistical evaluation of 15 years of surgical experience
      (Manuel Chanavaz, 1979-1994)].

PMID- 7569719
TI  - [A panorama of current materials for osseous application in maxillofacial surgery
      and oral implantology].
AB  - Many materials are used in bone reconstruction. According to their physico
      chemical structure, their activity is based on one of the three main mechanisms
      of bone repair: osteogenesis, osteoconduction, osteo-induction. The materials can
      be classified in two categories: tissues and substitution biomaterials. Tissues
      may be living ones (mainly, autograft) or non living ones (mainly, allograft or
      xenograft). Among the substitution biomaterials, we find synthetic materials
      (calcium based ceramics, vitreous ceramics and bioglasses, polymers) and
      composite materials made of a mixture of synthetic and natural materials or a
      mixture of different synthetic materials or a mixture of different synthetic
      materials. At last, membranes provide a new technic in bone reconstruction. They
      come from natural origin (human or animal) or synthetic origin (resorbable or non
      resorbable).

PMID- 7569722
TI  - Unusual clinical presentation of endotracheal mesenchymoma.
AB  - This report describes an unusual case of 35 year old man with endotracheal
      mesenchymoma. He was treated for two years as asthmoid bronchitis or asthma
      without any favourable result. The diagnosis was established by x-ray tomography
      and the patient was referred to the surgical treatment. The tumour was removed
      and the trachea was reconstructed. Postoperative course was very good. The
      patient is doing well without recurrence many years following the operation.

PMID- 7569721
TI  - Evaluation of the immune status in patients with primary and secondary Sjogren's
      syndrome.
AB  - The total white blood cell count, percentage and total count of lymphocytes,
      CD3+, CD4+, and CD8+ subpopulations of T-lymphocytes, population of CD20+ B
      lymphocytes, the ability of polymorphonuclears to phagocyte yeasts, the ability
      of polymorphonuclear cells to kill serum-resistant strain of E. coli and O2
      dependent killing capacity of polymorphonuclears were evaluated in a group of 10
      patients with the sicca syndrome and in a group of 9 patients with secondary
      Sjogren's syndrome and in a healthy control group. There was found a significant
      decrease in the relative and absolute counts of CD4+ helper/inducer T cells and
      in the activity of phygocytic cells in both groups of patients with Sjogren's
      syndrome as compared with the control group. There was no significant difference
      in the evaluated parameters between primary and secondary Sjogren's syndrome
      patients.

PMID- 7569720
TI  - [Risks and regulations related to materials used in implantology and
      maxillofacial surgery].
AB  - In the present paper, the authors call in mind the definitions of
      biocompatibility and the essential qualities required for biomaterials. The
      materials mostly used in implantology and maxillofacial surgery are numerous
      alloys, bioceramics, resorbable and non-resorbable polymers, and finally osseous
      substitutes of human or animal origin. As to synthetic and non-living materials,
      the risks in patients are generated by the degradation products. These may induce
      tissular reactions of inflammatory or immune origin owing to toxic effects.
      Concerning osseous substitutes, rejections are mostly of immune origin, for
      allografts and in particular for xenografts. Infections may be another major risk
      and in spite of all precautionary measures viral infections by hepatitis B, HIV
      and transmissible spongiform encephalopathy are not yet got under total control.
      It is just in these domains that one can state juristic lacks which national and
      european organisation of standardisation and homologation have to cover during
      the next few years.

PMID- 7569723
TI  - A technique for the evaluation of the left ventricle contraction.
AB  - A new method of left ventricle contraction evaluation using radiance is
      submitted. The reference point is not established a priori. It is the point where
      the function given by contraction variability and its magnitude has the minimum.
      This minimum can be considered as the contraction evaluating parameter.

PMID- 7569724
TI  - Proportional changes in the facial part of the skull of immature individuals.
AB  - The present study demonstrates the results of an evaluation of selected
      dimensions on the upper part of the splanchnocranium for a set of 98 skulls of
      immature individuals aged 6-18 (20) years, from the XIII.-XVIII. century.
      Prevailing growth changes related to age were determined on the basis of the
      craniometric measurements.

PMID- 7569725
TI  - Histochemical localization of succinate dehydrogenase in the mouse submandibular
      gland during postnatal development.
AB  - The activity of succinate dehydrogenase (SDH) was examined histochemically in the
      parenchyma of murine submandibular gland (SMG) during postnatal development on
      light-microscopical level. In this study, SDH appears as a good marker of
      differentiating and mature striated ducts of both sexes and convoluted granular
      tubules of males. Enzyme activity in glandular parenchyma increased from the 1st
      day to the 7th week of postnatal life. Definitive enzymatic pattern was seen in
      the gland aged 7 weeks. Histochemical differences between male and female SMG of
      mouse were noted.

PMID- 7569726
TI  - Impedance monitoring in the stereotactic localization of intracranial structures.
AB  - Measurement of tissue impedance is a simple objective method for the localization
      of intracranial structures. Continuous bipolar impedance monitoring was performed
      during various CT-guided stereotactic procedures in 36 patients with brain
      pathology. The obtained values of the impedance profile along the trajectory were
      compared with the tissue density on CT scans or angled coronal and sagital CT
      reconstructions intraoperatively. The main goal was the selection of optimal
      biopsy targets and safe probe trajectory. Histologic findings of serial
      transtumoral biopsy were retrospectively correlated with both CT (or MRI)
      transposed data and patterns of tissue impedance. Intraoperative impedance
      monitoring enhanced the accuracy and safety of CT-guided procedures. The
      histologic examination of representative tissue samples avoids the risks of
      "blind" surgical or radiation management. This technique is reported with 6
      illustrative cases.

PMID- 7569727
TI  - Extraadrenal pheochromocytoma.
AB  - During 35 years we operated on 44 patients with pheochromocytoma, 16 of them had
      extraadrenal tumors (36%). We operated on 8 men and 8 women. In 5 men there was
      primary extraadrenal tumor, the same in 7 women. In 3 men and in one woman we
      operated on recurrence of tumor on another site. Mean age of the whole group was
      38.3 years, in patients with recurrence the mean age was 44 years. Time distance
      between primary tumor and relapse was 3 to 16 years. We operated on 6 tumors on
      the right side, 10 on the left side. Paragangliomas on the right side were
      localized as follows: three tumors were under the vena cava, one tumor was
      dispersed multifocally, two tumors were localized before the vena cava. On the
      left side there was the following distribution of tumors: two tumors beneath the
      bifurcation of the aorta, 5 tumors paraaortally, one tumor on the wall of the
      aorta in the region of renal arteries, three tumors were localized in the hilus
      of the kidney.

PMID- 7569728
TI  - Cerebrospinal fluid dissemination of fetal neural isografts in brain of adult
      rats.
AB  - Our previous studies tend to document the temporary invasiveness of
      intraparenchymal fetal isografts. The present study exploits a model situation in
      which contacted host brain surface remains undamaged. We analyzed the behavior of
      transplant fragments that accidentally disseminated in cerebrospinal fluid
      pathways. The transplant seeding occurred in 7 cases out of 85 cases of healthy
      solid isografts taken from various parts of fetal brain. Fragments were found
      either as free (floating or simply lying close to the surface) or attached. Some
      attached fragments invasively penetrated the brain parenchyma. This speaks in
      favor of invasive properties of fetal neural transplants.

PMID- 7569729
TI  - Effects of high dose atrial natriuretic peptide on renal haemodynamics, sodium
      handling and hormones in cirrhotic patients with and without ascites.
AB  - To elucidate and to try to reverse the antinatriuretic mechanisms in liver
      cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus
      dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control
      to 14 healthy subjects. The nine patients with ascites had baseline values of
      glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood
      pressure (BP) similar to controls. Their distal tubular fractional reabsorption
      of sodium (DFRNa), estimated by the lithium clearance technique, was higher than
      in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1
      medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and
      cyclic GMP (8.8 vs. 4.6 nmol l-1); p < 0.01 for all. The five patients without
      ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls.
      After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in
      all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52
      mmol min-1, p < 0.01), while GFR increased (108 to 117 ml min-1, p < 0.05), and
      DFRNa decreased (93 to 89%, p < 0.01). In cirrhotics with ascites sodium
      excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml
      min-1). Proximal tubular fractional reabsorption of sodium increased after 90
      min, whereas DFRNa decreased immediately (97 to 96%, p < 0.01) though less
      markedly than in controls. Sodium excretion increased in four of five patients
      without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites,
      endothelin in plasma decreased after ANP (p < 0.05). Plasma levels of angiotensin
      II, aldosterone and vasopressin were unchanged in all groups. In conclusion,
      although hyper-reabsorption of sodium occurred in the distal rather than the
      proximal part of the nephron in cirrhotic patients with ascites, ANP had no
      natriuretic effect. This was most probably due primarily to the lack of increase
      of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The
      effect of ANP in suppressing the high endothelin did not seem to improve sodium
      excretion.

PMID- 7569730
TI  - IMx CA 125, an automated microparticle enzyme immunoassay: technical
      characteristics and clinical usefulness after recalibration.
AB  - A recently described automated microparticle enzyme immunoassay (Abbott IMx CA
      125) for cancer antigen 125 (CA 125) was recalibrated by the manufacturer to
      provide better agreement between the results of the IMx assay and other test
      methods for CA 125. The recalibrated microparticle enzyme immunoassay (MEIAII)
      had low imprecision (2.9-11.9%), a low detection limit (less than 0.48 kU l-1), a
      low carryover (less than 0.014%), and CA 125 was linearly recovered after
      dilution. CA 125 was measured during treatment of 138 patients with ovarian
      cancer and the MEIAII results were closely, but non-linearly, related to antigen
      values determined by a routinely used manual enzyme immunoassay (EIA) (Abbott CA
      125 EIA). EIA levels below 167 kU l-1 resulted in higher values when measured by
      the MEIAII and CA 125 concentrations above 167 kU l-1 in the EIA gave lower
      MEIAII values. CA 125 MEIAII and EIA measurements before a second-look laparotomy
      of 57 patients with ovarian cancer demonstrated that, using slightly different
      upper limits of normal values (MEIAII, 27 kU l-1; EIA, 20 kU l-1), the clinical
      information obtained from the MEIAII was equivalent to that obtained from the
      EIA. In conclusion, switching from the EIA to the MEIAII would indicate that
      series of samples should be analysed by both methods during a transfer period.
      The length of the period should depend on the obtained results.

PMID- 7569731
TI  - Serum Lp(a) lipoprotein levels in patients with coronary artery disease and the
      influence of long-term n-3 fatty acid supplementation.
AB  - The serum levels of Lp(a) lipoprotein (Lp(a)) were determined preoperatively in
      601 patients with coronary artery disease, undergoing bypass operations. Compared
      with a reference group of 99 apparently healthy individuals, the Lp(a) levels
      were higher in the patient group (7.7 mg dl-1 vs. 5.1 mg dl-1, p = 0.012). In the
      patient group, there was a weak, but significant negative correlation between the
      Lp(a) levels and age (r = -0.10, p = 0.017), and in both groups the women had
      higher Lp(a) levels than the men. In the patients we found no significant
      correlations between Lp(a) and other serum lipids or lipoproteins, nor between
      Lp(a) and variables in the fibrinolytic system. We investigated the long-term
      effects of supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) on
      the Lp(a) concentrations. Postoperatively, in a randomized fashion, 280 of the
      patients received 4 g of an n-3 PUFA concentrate (containing > 85% of long-chain
      n-3 PUFAs) per day, whereas 269 patients comprised the control group. The fatty
      acids in serum phospholipids were monitored, and a significant increase in the
      phospholipid n-3 fatty acids was noted in the n-3 PUFA group, as opposed to the
      virtually unchanged amounts in the control group. The Lp(a) levels were
      determined again after 6 months, and, compared with the control group, n-3 PUFA
      supplementation had no overall effect on the serum Lp(a) levels.

PMID- 7569732
TI  - Interpretation of blood lactate measurements in paediatric open-heart surgery and
      in extracorporeal membrane oxygenation.
AB  - For the purpose of demonstrating both the clinical value and economic advantages
      of using blood lactate as a marker for haemodynamic instability, we present the
      clinical guidelines for when to measure blood lactate and how these measurements
      are interpreted in two clinical settings: following open-heart surgery for
      complex congenital heart disease, and in determining both the need for and the
      effectiveness of extracorporeal membrane oxygenation (ECMO). Several case
      histories are presented that demonstrate the conditions which can elevate blood
      lactate concentrations and the resulting therapeutic interventions, based on use
      of volume support, inotropic support, vasodilators, and/or ventilation, that can
      lead to a successful outcome in these patients. In one of the case histories a
      greatly elevated blood lactate apparently indicated that intracranial hemorrhage
      had occurred in a patient who later expired.

PMID- 7569733
TI  - Lipoprotein(a) in relation to acute phase reaction in patients with rheumatoid
      arthritis and polymyalgia rheumatica.
AB  - The effect of altered inflammatory activity, as reflected by acute phase protein
      levels, on the concentration of lipoprotein(a) was analysed in 51 patients with
      rheumatoid arthritis (RA), and in 25 patients with polymyalgia rheumatica (PMR).
      Despite significantly decreased acute phase proteins in RA, the Lp(a)
      concentration increased significantly between the two observations in the group
      as a whole. In one subgroup with initially high Lp(a) levels, large
      intraindividual variations between the samplings and a high correlation to the
      ESR changes were found. Another subgroup with initially low levels showed small
      variations of Lp(a) without correlation to any acute phase reactant. In the PMR
      group, Lp(a) decreased in line with diminishing acute phase reactivity.

PMID- 7569734
TI  - Thyroid antibodies in association with thyroid malignancy II: Qualitative
      properties of thyroglobulin antibodies.
AB  - Qualitative properties of thyroglobulin (Tg) antibodies, in association with
      thyroid malignancy, suspected malignancy or other thyroid diseases, were studied
      in 177 patients. Retrospective clinical analysis revealed 137 patients to have
      thyroid carcinoma and 40 to have other thyroid diseases. Serum Tg was assayed by
      an immunoradiometric method. Thyroid microsomal (AMC) and Tg antibodies were
      measured by the particle agglutination method and the avidity of Tg antibodies by
      enzyme immunoassay (EIA). Assessment of the qualitative properties of Tg
      antibodies revealed that the high-avidity antibodies especially seem to bind
      circulating Tg. Thus any Tg value from a sample with detectable Tg antibodies is
      unreliable and should be interpreted with caution.

PMID- 7569735
TI  - Complex intracellular signal transduction regulates tissue plasminogen activator
      (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) synthesis in cultured
      human umbilical vein endothelium.
AB  - Endothelial cells are central in fibrinolysis because of their high production of
      both activators (t-PA, uPA) and inhibitors (PAI-1). The t-PA and PAI-1 synthesis
      could be regulated by signals transduction at several cellular levels. The
      purpose of this in vitro study, on cultured endothelial cells, was to explore the
      receptor/second messenger regulation of the t-PA and PAI-1 synthesis. Quiescent
      confluent human umbilical vein endothelial cells, cultured in passage 1, were
      exposed to different test substances. Samples from the conditioned medium were
      collected after 16 and 24 h and analysed for t-PA and PAI-1 antigen. All data
      presented were related to the data from control dishes (= 100%), in the same
      experiment. The results from the present study (mean +/- 95% confidence interval)
      demonstrated the following. (1) Forskolin, with a documented direct cAMP-inducing
      effect, decreased the basal PAI-1 production to 61 +/- 15%, and Na-nitroprusside,
      with a documented cGMP-inducing effect, increased the basal PAI-1 production to
      141 +/- 38% without affecting the basal t-PA production. The surface receptor
      agonists isoprenalin or ephedrine, which indirectly affect adenylate cyclase, had
      no effect on t-PA or PAI-1 production. (2) Phorbolester (PMA), which directly
      activates proteinkinase C (PKC), increased the basal t-PA and PAI-1 production to
      350 +/- 71%, and 163 +/- 35% respectively. (3) Thrombin, but not endothelin-1 (ET
      1), increased the basal t-PA and PAI-1 production to 195 +/- 34% and 136 +/- 18%,
      respectively, indicating an PKC-mediated thrombin effect.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7569736
TI  - An evaluation of twelve nested models of transperitoneal transport of urea: the
      one-compartment assumption is valid.
AB  - Models of transperitoneal urea transport are generally based on the one
      compartment assumption, i.e. that the plasma water urea concentration in the
      peritoneal capillary bed is equal to the plasma water urea concentration in the
      peripheral veins. The aim of this study was to investigate the mechanism(s) of
      transperitoneal urea transport and to test the one-compartment assumption for
      urea. A total of 12 nested models were formulated and validated on the basis of
      experimental results obtained from 23 non-diabetic patients undergoing peritoneal
      dialysis. The validation procedure demonstrated that transperitoneal transport of
      urea probably involves diffusion, non-lymphatic convection and lymphatic
      convection. It was furthermore demonstrated that the inclusion of lymphatic
      convection changes the mass transfer area coefficient considerably. Finally, no
      deviation from the one-compartment assumption was demonstrated by our results.

PMID- 7569737
TI  - Elimination of the non-ionic X-ray contrast media iodixanol and iohexol in
      patients with severely impaired renal function.
AB  - Iodixanol (Visipaque) and iohexol (Omnipaque) are dimeric and monomeric,
      respectively, non-ionic X-ray contrast media (CM), with well-characterized
      pharmacokinetics in healthy volunteers. This study was undertaken to study the
      pharmacokinetics of the contrast media in patients with severely impaired renal
      function. A total of 16 patients referred for preoperative abdominal angiography
      were randomized to form two groups of eight patients, receiving either iodixanol
      320 mgI ml-1 or iohexol 350 mgI ml-1. Urine and faeces were sampled before the
      examination and collected quantitatively for five days afterwards, and blood
      samples were drawn frequently. The concentrations of iodine and contrast medium
      in urine and in serum, and the amount of iodine in faeces were determined. Mean
      baseline creatinine clearance was 13.6 and 9.9 ml min-1 1.73 m-2 in the iodixanol
      and iohexol groups, respectively. Patients in the iodixanol group received on
      average 0.34 gI per kg bodyweight (bw) and those in the iohexol group 0.39 gI per
      kg bw. The semilogarithmic plots of serum concentration of CM vs. time indicated
      elimination according to a two-compartment model. The mean elimination half-life
      was 23.0 h for iodixanol and 27.2 h for iohexol, and the mean apparent volume of
      distribution was similar for the two CM, ranging from 0.20 to 0.30 1 per kg bw.
      Mean plasma clearance of iodixanol was 10.4 ml min-1 1.73 m-2 and 6.9 ml min-1
      1.73 m-2 for iohexol, whereas the mean renal clearances were 8.7 and 6.1 ml min-1
      1.73 m-2, respectively. Mean faecal recovery was 8.2% for iodixanol and 6.1% for
      iohexol, and the respective figures for that in urine were 76.1 and 74.8%. Renal
      clearance of radiolabelled iothalamate, a marker of glomerular filtration rate
      (GFR), measured simultaneously, indicated that both CM were eliminated by the
      kidneys by glomerular filtration only. Thus, both media are suitable as GFR
      markers.

PMID- 7569738
TI  - Hypercholesterolaemia of prolonged fasting and cholesterol lowering of re-feeding
      in lean human subjects.
AB  - Serum cholesterol and triglycerides were determined in 36 lean, healthy adults
      (mean body mass index = 24.3 +/- 0.4 kg m-2) during a period of fasting of 7-21
      days. Fasting for 1 week resulted in significant elevation of serum cholesterol
      (mean increase 25%, range 0-68) and triglycerides (mean increase 24%). No
      correlation was observed between pre-fast cholesterol level and fasting-induced
      hypercholesterolaemia. Continued fasting for up to 21 days resulted in lowering
      of both cholesterol and triglycerides to pre-fast levels. One week of hypocaloric
      re-feeding resulted in significantly lower than pre-fast cholesterol (mean
      decrease 13%) and significantly higher than prefast triglycerides (mean increase
      86%). The net change in serum cholesterol observed as a result of fasting and re
      feeding correlated with prefast cholesterol (r = -0.6901, p = 0.0001). No
      significant change in the ratio of unesterified cholesterol to total cholesterol
      was observed during fasting. Fasting for 3 weeks followed by 1 week of
      hypocaloric re-feeding, however, resulted in a significant (p = 0.05) increase in
      this ratio from 0.27 +/- 0.0057 to 0.34 +/- 0.01. Fasting for 1 or 2 weeks
      followed by re-feeding also resulted in a similar increase in the ratio of
      unesterified cholesterol to total cholesterol. Cholesterol in the HDL fraction
      remained within normal range throughout the fasting and re-feeding period, with
      no significant changes between time points.

PMID- 7569740
TI  - Application of time series analysis in the clinical setting.
AB  - A growth curve time series model is characterized by a biological growth pattern
      with random deviations added to this basic pattern. Various types are reviewed
      including the homeostatic model which is a special and simple type characterized
      by zero growth. The limitations to the use of time series analysis in the
      clinical setting include lack of initial baseline values and difficulties in
      specifying in quantitative terms a relevant hypothesis alternative to the one
      postulated by the time series model. Some ongoing research addressing these
      problems is discussed.

PMID- 7569739
TI  - Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems
      during and after open heart surgery in children.
AB  - Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems
      may be responsible for some of the coagulation disorders and inflammatory
      sequelae seen after extracorporeal circulation. The activation pattern of these
      systems was studied in 10 children undergoing open heart surgery with
      extracorporeal circulation. Blood samples were drawn serially before, during and
      up to 48 h after surgery. The heparin injection induced a significant elevation
      of plasmin (PL) (p < 0.05) which stayed elevated during extracorporeal
      circulation. Antiplasmin (AP) values were reduced at wound closure, while the
      levels were significantly elevated 48 h postoperatively (p < 0.05). alpha 2
      antiplasmin-plasmin (APP) increased significantly perioperatively peaking 10 min
      after the initiation of cardiopulmonary bypass (p < 0.05). The coagulation
      markers thrombin-antithrombin (TAT) and the prothrombin fragment F1 & 2 increased
      significantly, peaking at wound closure and at termination of bypass respectively
      (p < 0.05). Plasma kallikrein (KK) values increased significantly with subsequent
      decreased levels of prekallikrein (PKK) and kallikrein inhibitor (KKI) after
      heparin injection. The KK level stayed elevated during cardiopulmonary bypass
      (CPB). The proenzyme functional inhibition index (PFI index), defined as the sum
      of deviations from the control values for proenzyme and functional inhibition
      values of the coagulation, fibrinolytic and plasma kallikrein-kinin systems,
      correlated significantly to the duration of cardiopulmonary bypass (p < 0.05). We
      conclude that open heart surgery in children activates the fibrinolytic,
      coagulation and plasma kallikrein-kinin systems.

PMID- 7569742
TI  - Computational intelligence for laboratory information systems.
AB  - Non-linear models, such as given by neural networks and fuzzy logic, have
      established a good reputation for medical data analysis as computational and
      logical counterparts to statistical methods. Whereas multilayer perceptrons
      perform well with large data sets, a combination of neural learning together with
      fuzzy logical network interpretations provides a network reduction well suited
      for smaller data sets. The aim of this paper is to present an approach to neural
      fuzzy systems data analysis and knowledge acquisition in laboratory information
      systems. We also describe a software system, DiagaiD, which provides an analysis
      and development workbench involving laboratory data.

PMID- 7569741
TI  - Possibilities for quality assurance of reference intervals.
AB  - Most clinical laboratories participate in surveys of external quality assurance
      (EQA). The results are not, however, very commonly or effectively applied to
      controlling the accuracy, i.e., differences in the analytical level. Therefore,
      it is important that each laboratory has its own, valid reference values.
      Nevertheless, many laboratories do not follow the internationally accepted
      recommendations for determining reference intervals or use reference values from
      other laboratories or from literature. Techniques of the external quality
      assurance can be extended to the checking of the validity of reference limits.

PMID- 7569743
TI  - Multivariate reference regions.
AB  - A high frequency of "false positive" conclusions is often the outcome when
      several laboratory test results are interpreted by comparing each single test
      result with the corresponding reference interval, i.e., by multiple univariate
      comparisons. The adequate solution to this problem is the application of a
      multivariate reference region for the test profile. This region is a
      straightforward extension of the univariate reference interval to the
      multidimensional situation.

PMID- 7569744
TI  - Using computerized individual medication data to detect drug effects on clinical
      laboratory tests.
AB  - In clinical practice, thousands of drugs are used daily. Clinicians know the
      therapeutic effects of drugs but other minor drug effects are often ignored
      either because of inadequate knowledge of these effects or simply because of the
      limited memory capacity of a human being. This problem can be solved by using a
      computerized information system, which includes medication data of individual
      patients as well as information about non-therapeutic drug-effects. One of these
      non-therapeutic confusing drug effects is the influence of drugs on laboratory
      tests; a problem that should be taken into account in clinical practice and
      diagnostics. Other complicating drug effects include drug interactions and
      patient related adverse drug reactions. In a computerized information system, it
      is possible to build decision support modules that automatically give alarms or
      alerts of important drug effects other than therapeutic effects. If these
      warnings concern laboratory tests they are checked by a laboratory physician and
      only those with clinical significance are sent to clinicians. Warnings of drug
      interactions and adverse drug reactions are immediately evaluated by the
      physician responsible for the treatment. By means of the computerized information
      system, it is also possible to get better information of current medication
      practice which in turn gives better chances to agree on common guidelines and
      enables better quality assurance.

PMID- 7569745
TI  - Estimation of reference change limits using patient data.
AB  - Two approaches for deriving reference change limits from patient data are
      described. In the direct method, hospital database information is used for the
      selection of appropriate reference groups. If database information is not
      sufficient or reliable enough, but still most of the source data can be
      considered as health-related, an indirect method can be applied in the
      calculation of rough estimates for reference change limits. A computer program
      developed by us, GraphROC for Windows, includes both methods for the estimation
      of change limits from patient data. Time between specimen collections should be
      included as one classifying factor in the selection of source data. When only one
      previous result is available for comparison, change limits based on the reference
      sample group form the only available guide for clinical interpretation. However,
      when several previous results are available and the within-subject variances for
      the considered analyte are known to be heterogeneous between individuals, the
      clinical interpretation should rather be based on application of time series
      analysis.

PMID- 7569746
TI  - Software for illustrative presentation of basic clinical characteristics of
      laboratory tests--GraphROC for Windows.
AB  - GraphROC for Windows is a program for clinical test evaluation. It was designed
      for the handling of large datasets obtained from clinical laboratory databases.
      In the user interface, graphical and numerical presentations are combined. For
      simplicity, numerical data is not shown unless requested. Relevant numbers can be
      "picked up" from the graph by simple mouse operations. Reference distributions
      can be displayed by using automatically optimized bin widths. Any percentile of
      the distribution with corresponding confidence limits can be chosen for display.
      In sensitivity-specificity analysis, both illness- and health-related
      distributions are shown in the same graph. The following data for any cutoff
      limit can be shown in a separate click window: clinical sensitivity and
      specificity with corresponding confidence limits, positive and negative
      likelihood ratios, positive and negative predictive values and efficiency.
      Predictive values and clinical efficiency of the cutoff limit can be updated for
      any prior probability of disease. Receiver Operating Characteristics (ROC) curves
      can be generated and combined into the same graph for comparison of several
      different tests. The area under the curve with corresponding confidence interval
      is calculated for each ROC curve. Numerical results of analyses and graphs can be
      printed or exported to other Microsoft Windows programs. GraphROC for Windows
      also employs a new method, developed by us, for the indirect estimation of health
      related limits and change limits from mixed distributions of clinical laboratory
      data.

PMID- 7569747
TI  - Finding the "natural" vector bases for multidimensional reference values.
AB  - The concept of reference values can be extended to multidimensional results. A
      probability function describes the relative density of the observations in the
      multivariate space. When the density of a given point is measured relative to all
      other points, we get an estimate of the density rank of a given point. If the
      rank of a point is lower than 95 per cent of all points, the multidimensional
      result is outside the multidimensional reference range. The single-dimensional
      case is a special case of this general concept. Many observations are needed to
      define multidimensional distributions. However, less points are needed if the
      dimensionality of the data matrix is reduced by statistical methods such as
      principal component analysis (PCA). Also other vector bases than the orthogonal
      solution produced by PCA are possible, and all of them compress data equally
      well. So the choice must be based on other criteria than compression. We propose
      using a vector basis that consists of positive numbers. The positive vectors can
      be found by direct methods such as Alternating Regression (AR) or they can be
      modified from the results of the PCA. Positive vectors resemble the spectra that
      are familiar in chemistry and physics. They are a "natural" way to describe
      multidimensional results. It is easier to name the positive vectors than the
      purely statistical vectors of PCA. To obtain a unique positive solution,
      additional constraints besides positivity are needed.

PMID- 7569748
TI  - Reliability and adequacy of discharge diagnosis databases in the production of
      reference values.
AB  - Discharge diagnoses provide a possibility to select patients individually and
      then to establish reference values for both "pathological" and control groups.
      Currently, the available diagnostic information is still at its infancy and
      should be carefully evaluated before the reference values based on those groups
      are utilized. It is anticipated that electronic storage of diagnostic and
      therapeutic information will be applied more commonly in the future as the
      development of computers makes it easier. The advanced utilization of laboratory
      data challenges physicians both in the clinical and laboratory side to
      participate in this development in order to make the information systems serve
      their actual needs more closely.

PMID- 7569750
TI  - Using data preprocessing and single layer perceptron to analyze laboratory data.
AB  - During daily work in hospitals a large amount of clinical data is produced each
      day. Totally computerized patient records are not yet widely used but a large
      part of essential information is already stored on computer files. These include
      laboratory test results, diagnoses, codes for operations, codes of
      histopathological diagnoses and maybe even the patient's medication. Accordingly,
      these databases include much clinical knowledge that would be useful for
      clinicians. Laboratories try to support clinicians by producing reference values
      for laboratory tests. It is, of course, necessary information but, however, it
      does not give very much information about the weight of evidence that an abnormal
      laboratory test will give in special clinical settings. We have developed a
      software package - DiagaiD - in order to build a smart link between patient
      databases and clinicians. It utilizes neural network-based machine learning
      techniques and can produce decision support which meets the special needs of
      clinicians. From example cases it can learn clinically relevant transformations
      from original numeric values to logical values. By using data transformation
      together with a single layer perceptron it is possible to build nonlinear models
      from a set of preclassified example cases. In this paper, we use two small
      datasets to show how this scheme works in the diagnosis of acute appendicitis and
      in the diagnosis of myocardial infarction. Results are compared with those
      obtained using logistic regression or backpropagation neural networks. The
      performance of our neuro-fuzzy tool seemed to be slightly better in these two
      materials but the differences did not reach statistical significance.

PMID- 7569749
TI  - Subject-based reference values.
AB  - Medical decisions based on comparison with group-based reference value have often
      less than desired sensitivity to significant changes in the biochemical or
      physiological state of an individual under investigation. Subgrouping of the
      reference values according to sex, age, or other criteria does frequently not
      solve this problem. The better solution is to compare new values with old results
      from the same individual, i.e., with subject-based reference values. Two types of
      criteria may be used: those based on critical differences between two results
      (the reference change limit) and those based on time-series models.

PMID- 7569751
TI  - Application of neural networks to the ranking of perinatal variables influencing
      birthweight.
AB  - In this paper we compare Multi-Layer Perceptrons (a neural network type) with
      Multivariate Linear Regression in predicting birthweight from nine perinatal
      variables which are thought to be related. Results show, that seven of the nine
      variables, i.e., gestational age, mother's body-mass index (BMI), sex of the
      baby, mother's height, smoking, parity and gravidity, are related to birthweight.
      We found no significant relationship between birthweight and each of the two
      variables, i.e., maternal age and social class.

PMID- 7569752
TI  - Effect of platelet count on serum and plasma potassium: evaluation using database
      information from two hospitals.
AB  - The availability of retrospective data from potassium (K+) analyses from two
      hospitals, one using serum and the other plasma for electrolyte measurements,
      offered us the possibility to investigate the effect of blood platelet count on
      serum and plasma K+ concentrations. A weak correlation between plasma K+ and
      platelet count was observed. The in vitro increase of serum K+ in proportion to
      the platelet count has clinical significance in conditions, where it may impede
      the detection of an underlying true K+ disorder. Nomograms and correction
      factors, based on the correlation between platelet count and serum K+, have been
      suggested also in some recent reports. In the present study unselected routine
      patient data was used as source data. The effect of platelet count on the
      concentration of K+ in serum was lower than reported in previous studies, as
      indicated by the regression analysis. An increase of 1000 x 10(9)/l in the blood
      platelet count would cause an increase of about 0.7 mmol/l in the serum K+
      concentration (p < 0.0001, r = 0.155). The weak correlation between platelet
      count and serum K+ does not support the application of platelet-count-based
      correction of serum K+ level in thrombocytosis. The laboratory should notify the
      clinician of the significance of the in vitro increase of K+ caused by increased
      platelet count. K+ should be measured from plasma in such cases.

PMID- 7569753
TI  - The role of lactic acid bacteria in colon cancer prevention.

PMID- 7569754
TI  - Effect of gastrin receptor blockade on gastrin and histidine decarboxylase gene
      expression in rats during achlorhydria.
AB  - BACKGROUND: Gastrin stimulates histidine decarboxylase (HDC) activity and
      proliferation of enterochromaffin-like (ECL) cells. Furthermore, it has been
      suggested that gastrin controls HDC gene expression. We therefore analysed the
      effect of gastrin receptor blockade by PD 136 450 (CAM 1189) on HDC gene
      expression. The influence of PD 136 450 on gastrin, somatostatin, and
      chromogranin A was also evaluated. METHODS: Gene expression of HDC, gastrin,
      somatostatin, and chromogranin A (CgA) was analysed by Northern blot analyses
      after 14 days' application of the proton pump inhibitor BY 308 and/or the
      gastrin/cholecystokinin B receptor antagonist PD 136 450. RESULTS: PD 136 450 had
      no significant effect on gastrin mRNA or somatostatin mRNA in controls and during
      proton pump inhibition. BY 308 treatment resulted in a marked induction of HDC
      and CgA mRNA, whereas concomitant PD 136 450 in a concentration previously shown
      to suppress maximal pentagastrin-induced gastric acid secretion and to prevent BY
      308-induced ECL cell proliferation did not result in significant alteration. PD
      136 450 increased HDC significantly and CgA mRNA to a lesser extent in
      normogastrinaemic rats, whereas previous work showed a decreased ECL cell
      labelling index. CONCLUSIONS: These data suggest that there are independent
      regulatory pathways for ECL cell proliferation and gene expression. Other factors
      besides gastrin may act through PD 136 450-insensitive pathways to control HDC
      and CgA gene expression.

PMID- 7569755
TI  - Pantoprazole and ranitidine in the treatment of acute duodenal ulcer. A
      multicentre study.
AB  - BACKGROUND: Pantoprazole is a new substituted benzimidazole that inhibits the
      parietal cell H+,K(+)-adenosine triphosphatase. METHODS: Pantoprazole (40 mg) was
      compared with ranitidine (300 mg) in the treatment of acute duodenal ulcer. Two
      hundred and sixty-six patients with endoscopically diagnosed duodenal ulcers
      entered this multicentre, double-blind study. The primary efficacy variable was
      complete ulcer healing at 2 weeks; treatment then continued for a further 2 weeks
      if ulcers were unhealed. RESULTS: After 2 weeks 112 of 164 (68%) patients in the
      pantoprazole group had healed ulcers, compared with 36 of 81 (44%) taking
      ranitidine (p < 0.001). After 4 weeks the cumulative healing rates were 96% and
      85% (p < 0.01). Improvement in ulcer pain was also significantly better with
      pantoprazole than with ranitidine (81% versus 62% with no pain at 2 weeks, p <
      0.01). CONCLUSIONS: Pantoprazole is clinically superior to ranitidine in the
      treatment of acute duodenal ulcer, in terms of both healing and symptom relief.

PMID- 7569756
TI  - Evidence of de novo collagen synthesis in healing human gastric ulcers.
AB  - BACKGROUND: The fibrillar collagens, types I and III, have been demonstrated in
      healthy human gastric mucosa as well as in the submucosa of gastric ulcer edges,
      where they are remarkably increased. METHODS: To verify the occurrence and
      activity of de novo collagen synthesis, we examined gastric biopsy specimens from
      six patients with antral ulcers and six normal controls. By means of in situ
      hybridization, using a 35S-labeled RNA probe, we could localize the specific
      procollagen mRNA for type-I collagen. RESULTS: In normal gastric mucosa this mRNA
      was expressed by only a very limited number of cells, whereas at the ulcer edges
      the specific signal could be demonstrated in a large number of submucosal cells.
      CONCLUSION: These results suggest a substantial role of fibroneogenesis in the
      process of gastric ulcer healing.

PMID- 7569757
TI  - Etiology of dyspepsia: four hundred unselected consecutive patients in general
      practice.
AB  - BACKGROUND: Four hundred consecutive unselected patients with dyspepsia in health
      care centers were investigated. The aim of this study was to assess the frequency
      of various causes of dyspepsia in primary care and to evaluate the usefulness of
      the latest definition of functional dyspepsia. METHODS: Upper gastrointestinal
      endoscopy, upper abdominal ultrasound, a test for lactose intolerance, and basic
      laboratory screening were performed in every patient. RESULTS: Esophagitis was
      the cause of symptoms in 15%, symptomatic gastroesophageal reflux without
      esophagitis in 12%, duodenal ulcer in 9%, gastric ulcer in 4%, erosive duodenitis
      in 2%, lactose intolerance in 9%, gallstone disease in 2%, and malignancy in 2%.
      Other more infrequent causes of dyspepsia were giardiasis, celiac disease,
      erosive gastritis, and chronic pancreatitis. One hundred and thirty-five patients
      had functional dyspepsia with subgroups of ulcer-like (22%), dysmotility-like
      (28%), and nonspecific (50%). Irritable bowel syndrome was diagnosed in 37
      patients (9%). CONCLUSIONS: The cause of dyspepsia was organic in 45%. Functional
      disorders, when symptomatic gastroesophageal reflux was included, were diagnosed
      in 55%. The latest classification of functional dyspepsia is not in accordance
      with the symptom complex.

PMID- 7569759
TI  - A double-blind, randomized, placebo-controlled trial of cisapride in Saudi Arabs
      with functional dyspepsia.
AB  - BACKGROUND: Trials on functional dyspepsia (FD) have been performed mostly in
      Western populations. We evaluated the effect of cisapride in Saudi Arabs with FD.
      METHODS: In a double-blind, randomized, placebo-controlled trial patients were
      treated with cisapride three times daily or matching placebo and assessed at 2
      and 4 weeks. RESULTS: Cisapride (n = 44) was significantly superior to placebo (n
      = 45) in improving heartburn, postprandial bloating, epigastric pain, early
      satiety, epigastric burning, and nausea. The global response to treatment was
      excellent or good in 86.7% and 26.7% of the cisapride and placebo groups,
      respectively. Treatment was judged more effective than the previous therapy in
      86.4% and 33.3% of those receiving cisapride and placebo, respectively. There
      were no adverse drug effects. CONCLUSIONS: Cisapride is an effective and well
      tolerated treatment for FD in Saudi Arabs. Pharmacogenetic factors are unlikely
      to play any role in its effects.

PMID- 7569758
TI  - Life events and stress in patients with functional dyspepsia compared with
      patients with duodenal ulcer and healthy controls.
AB  - BACKGROUND: Life events and stress may be important for functional dyspepsia and
      duodenal ulcer. METHODS: The perception of life events in the preceding 6 months
      was recorded in 100 patients with functional dyspepsia, 100 patients with
      duodenal ulcer, and 100 healthy controls. In addition, psychologic and social
      factors were assessed. RESULTS: Patients with functional dyspepsia experienced
      significantly more life events than patients with duodenal ulcer and healthy
      controls. The difference in life events between the groups was due to the
      difference in stressful life events. The patients with functional dyspepsia had
      higher levels of state-trait anxiety, general psychopathology, and depression
      than patients with duodenal ulcer and healthy controls. CONCLUSION: Patients with
      functional dyspepsia had higher scores on negative life events than patients with
      duodenal ulcer and healthy controls. This may be causally related to the higher
      levels of anxiety, depression, and general psychopathology in these patients.

PMID- 7569761
TI  - Helicobacter pylori-associated gastritis. Evolution of histologic changes over 10
      years.
AB  - BACKGROUND: Helicobacter pylori seems to be the commonest cause of chronic
      gastritis, but the natural course of H. pylori-associated gastritis is largely
      obscure. METHODS: We present a histologic follow-up of 39 patients with H. pylori
      positive gastritis. Gastroscopies with stepwise biopsies were performed in all
      the patients at an interval of 10 years. RESULTS: Of the patients 87% (34/39) had
      a persistent infection and showed a significant decrease in the grades of antral
      gastritis, eosinophilic granulocytes, corpus eosinophilic granulocytes, and
      foveolar hyperplasia and a significant increase in the grade of corpus
      neutrophilic granulocytes. The quantities of H. pylori as estimated
      histologically did not change significantly during the follow-up period in
      patients with a persistent infection. In the five other patients (13%) the H.
      pylori infection had apparently disappeared spontaneously, and this was
      accompanied by decreases in the amount of inflammatory cells in the gastric
      mucosa. CONCLUSIONS: H. pylori infection in the gastric mucosa is chronic and may
      be associated with both regressive and progressive histologic changes.
      Spontaneous healing of H. pylori infection is possible and is associated with
      partial resolution of the inflammatory changes in the gastric mucosa.

PMID- 7569760
TI  - Oral cromolyn sodium in comparison with elimination diet in the irritable bowel
      syndrome, diarrheic type. Multicenter study of 428 patients.
AB  - BACKGROUND: In a significant number of patients affected by the irritable bowel
      syndrome, an adverse reaction to food is proposed to be a causative factor. A
      diet that eliminates the offending foods is the obvious treatment for such
      adverse reactions. Compliance with a dietetic regimen is often poor and sometimes
      not completely free from risks. METHODS: Since the diarrheic type of irritable
      bowel syndrome seems mainly affected by food intolerance, and previous
      observations suggested that oral cromolyn sodium is effective in such patients, a
      multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome
      was carried out in 346 of 409 patients with this disease, to evaluate the effects
      of oral cromolyn sodium and compare its efficacy with that of an elimination
      diet. RESULTS: Symptoms related to the irritable bowel syndrome improved in 60%
      of patients treated with elimination diet and in 67% of those treated with oral
      cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical
      results were significantly better in the patients positive to the skin prick test
      than in the negative ones. CONCLUSIONS: These results confirm the high prevalence
      of adverse reactions to foods in diarrheic irritable bowel syndrome and the
      usefulness of cromolyn sodium treatment in these patients.

PMID- 7569762
TI  - Helicobacter pylori infection is associated with low antral somatostatin content
      in young adults. Implications for the pathogenesis of hypergastrinemia.
AB  - BACKGROUND: Recent studies on the role of Helicobacter pylori in the pathogenesis
      of duodenal ulcers have focused on the mechanism by which H. pylori infections
      cause exaggerated gastrin release. METHODS: We determined meal-stimulated serum
      gastrin concentrations and antral somatostatin content in 24 asymptomatic
      volunteers (6 H. pylori-infected, 18 H. pylori-uninfected). Somatostatin content
      was determined by radioimmunoassay in biopsy specimens obtained from the antrum.
      RESULTS: Fasting and integrated 2-h gastrin concentrations were significantly
      higher in H. pylori-positive volunteers than in H. pylori-negative volunteers
      (fasting, 111 +/- 16.3 pmol/l versus 53.4 +/- 3.5 pmol/l; p < 0.05; integrated 2
      h, 267 +/- 41.2 pmol/l versus 70.1 +/- 2.1 pmol/l; p < 0.01). Antral somatostatin
      content was 0.764 +/- 0.173 ng/mg and 2.931 +/- 0.414 ng/mg in H. pylori-positive
      and -negative volunteers, respectively (p < 0.01). CONCLUSIONS: Low antral
      somatostatin content may cause hypergastrinemia in asymptomatic healthy
      volunteers, and H. pylori may contribute to the pathogenesis of duodenal ulcer,
      through this mechanism.

PMID- 7569763
TI  - Intestinal intraluminal continuity is a prerequisite for the distal bowel
      motility response to feeding.
AB  - BACKGROUND: We wanted to elucidate further the regulation of the intestinal
      motility response to feeding. METHODS: After intraduodenal administration of an
      oleate solution, mimicking a meal, the distal bowel motility and the plasma
      levels of bile acids, cholecystokinin (CCK), and neurotensin were monitored in
      patients operated on with restorative proctocolectomy (n = 4) or low anterior
      resection of the rectum (n = 4). Investigations were performed both with and
      without a diverting loop ileostomy. RESULTS: Intraduodenal sodium oleate elicited
      a prompt and significant increase in distal bowel motility. The motility response
      failed to appear when the luminal flow was diverted by a loop ileostomy. An
      increase in plasma CCK preceded the motility increase, but CCK was increased also
      in patients with a loop ileostomy. Whereas plasma bile acid levels were
      significantly increased after 30-45 min (p < 0.05), both with and without a loop
      ileostomy, neurotensin levels were not affected. CONCLUSION: Intestinal
      continuity is a prerequisite for the distal bowel motility response, indicating
      that apart from other possible mechanisms, luminal factors are involved in the
      regulation of intestinal motility.

PMID- 7569764
TI  - Ascending colon response to feeding: evidence for a 5-hydroxytryptamine-3
      mechanism.
AB  - BACKGROUND: The role of serotonergic type-3 receptors in proximal human colon is
      unclear. Our aims were to assess the postprandial volume and emptying of the
      ascending colon and to explore the role of 5-hydroxytryptamine-3 (5HT3)
      mechanisms. METHODS: In healthy subjects with unprepared colons we evaluated in a
      randomized trial the effects of the 5HT3 antagonist ondansetron (n = 5) or
      placebo (n = 5) on ascending colon volume and emptying, using a scintigraphic
      method. RESULTS: Base-line ascending colon volumes were similar and were
      unaltered by ondansetron. After a 1000-kcal liquid meal the placebo group showed
      a variable change in volume (P = NS versus base line) during the first 25 min
      (median, -4%; range, -13% to 135%). Increases in volume during this period
      coincided with ileal emptying of chyme. During a second phase (30-105 min) there
      was a significant decrease of ascending colon volume (P = 0.02) relative to the
      early postprandial volume, but the volume was not significantly different from
      base line. This second phase was associated with transfer of chyme towards the
      transverse colon. In the ondansetron group there was an initial modest increase
      in volume (median, 5%; range, -15% to 14%; P = NS versus base line), and the
      second phase of contraction was inhibited. CONCLUSIONS: The ascending colon
      response to a meal in health is characterized by a variable initial change in
      volume, accommodating ileal chyme in some individuals, and a more consistent
      reduction in volume from 30 to 105 min postprandially. The latter response is
      inhibited by ondansetron, suggesting partial control of postprandial colonic
      motor function by 5HT3 mechanisms.

PMID- 7569766
TI  - Intakes of nutrients and nutritional status in coeliac patients.
AB  - BACKGROUND: The intake of nutrients and the nutritional status of untreated
      coeliac patients and coeliac patients in remission were investigated at Kuopio
      University Hospital. METHODS: Forty untreated and 52 coeliac patients in
      remission were admitted to the study. The control group included 77 persons. Four
      day food records, anthropometric measurements, and blood biochemistry were
      examined to obtain nutrient intake and nutritional status. RESULTS:
      Concentrations of serum ferritin, vitamin B12, and erythrocyte folate were lower
      in patients with untreated coeliac disease than in those in remission.
      Altogether, 15-38% of the untreated patients but only 0-20% of the patients in
      remission had levels of haemoglobin, serum ferritin, iron, vitamin B12, or
      erythrocyte folate below the reference values. No difference in anthropometric
      measurements was found between the two groups of coeliac patients. CONCLUSIONS:
      Except for some subclinical abnormal values in biochemical analyses in 20-38% of
      coeliac patients, nutritional status was quite normal in both groups of coeliac
      patients.

PMID- 7569765
TI  - Release of peptide YY by neurotransmitters and gut hormones in the isolated,
      vascularly perfused rat colon.
AB  - BACKGROUND: Peptide YY (PYY) is promptly released from endocrine cells of the
      distal part of the gut after food intake. To test the possibility that hormones
      produced by the proximal small intestine or transmitters of the enteric nervous
      system may take part in the early phase of meal-induced PYY release, various
      regulatory peptides and neurotransmitters of the gut were administered intra
      arterially in the isolated, vascularly perfused rat colon. METHODS: A colonic
      loop was perfused with a Krebs-Henseleit buffer containing 20% washed bovine
      erythrocytes via the superior mesenteric artery. The release of PYY in portal
      effluent was measured by radioimmunoassay. RESULTS: Cholecystokinin and secretin
      produced a small release of PYY. In contrast, infusion of gastric inhibitory
      polypeptide (GIP) over the concentration range 0.25-1 nM for 30 min produced a
      dose-dependent secretion of PYY with a maximal response at 800% above basal.
      Tetrodotoxin (TTX) did not modify the GIP-induced PYY release. Bethanechol (10(
      5) M, 10(-4) M) produced a PYY release that was maximal at the end of the 30-min
      infusion period. The beta-adrenergic agonist isoproterenol (10(-7) M, 10(-6) M)
      caused a prompt release of PYY, followed by a sustained release at a lower value.
      Calcitonin gene-related peptide (CGRP) (5.10(-9) M and 5.10(-8) M) induced a PYY
      release with kinetics similar to that found for isoproterenol. Finally, bombesin
      (10(-9)-10(-7) M) provoked a dose-dependent release of PYY, consisting of an
      early peak followed by a sustained response. TTX did not modify the bethanechol-,
      isoproterenol-, CGRP-, and bombesin-induced PYY secretion. CONCLUSION: The
      hormonal peptide GIP and several transmitters of the nervous enteric system may
      mediate the release of PYY through the occupation of receptors possibly located
      at the surface of the colonic L-cells.

PMID- 7569768
TI  - Secretion of gastric inhibitory polypeptide in patients with bile duct
      obstruction.
AB  - BACKGROUND: The direct contribution of bile to gastric inhibitory polypeptide
      (GIP) release and the role of bile in regulating GIP secretion in response to fat
      ingestion are still obscure. The present study was aimed to clarify the influence
      of bile on GIP release. METHODS: Seven patients with obstruction of the common
      bile duct and nine volunteers participated in the study. Fifty milliliters of
      Lipomul was ingested, and GIP was measured serially for 180 min. After
      intraduodenal instillation of pooled autologous bile for 2 days, the same study
      was carried out. RESULTS: The fat-stimulated GIP response was significantly lower
      in the patients than in the controls. The basal GIP level did not change on bile
      instillation, but the GIP response to fat ingestion was significantly increased
      on bile instillation compared with that in the absence of bile. CONCLUSIONS:
      Intraluminal bile alone does not stimulate the secretion of GIP, but it promotes
      GIP secretion in response to fat ingestion.

PMID- 7569767
TI  - Fibrinolytic split products, fibrinolysis, and factor XIII activity in
      inflammatory bowel disease.
AB  - BACKGROUND: Factor XIII (F XIII), the last coagulation factor in the clotting
      cascade, plays a role in mucosal repair. Beneficial effects of F XIII
      supplementation in severe ulcerative colitis (UC) have been observed. The aim of
      this study was to relate plasma F XIII activity to the severity of inflammatory
      bowel disease (IBD). METHODS: A transversional and, in part, longitudinal study
      of F XIII activity and related clotting products was performed in 39 patients
      with UC, 31 patients with Crohn's disease (CD), and 20 controls. Disease activity
      was assessed with a combined activity score in UC and with the Dutch Activity
      Index in CD. RESULTS: F XIII activity was decreased in active UC (p < 0.05) and
      active CD (p < 0.05) and was inversely correlated with severity in both UC (r = 
      0.30) and CD (r = -0.46). In six patients with UC (15%) and six patients with CD
      (19%) F XIII activity was below the lower range of normal. In these patients
      apparent rectal bleeding was only found in severe UC. Hyperfibrinolysis was
      indicated by elevated levels of D-dimer (p < 0.001) notwithstanding increased
      concentrations of alpha-2 antiplasmin (p < 0.05). CONCLUSIONS: In active IBD we
      found decreased plasma F XIII activity and hyperfibrinolysis. Decreased F XIII
      activity was not associated with apparent rectal bleeding in IBD.

PMID- 7569769
TI  - Protective effects of calcium channel blockers on acute bromobenzene toxicity to
      isolated rat hepatocytes. Inhibition of phenylephrine-induced calcium
      oscillations.
AB  - BACKGROUND AND METHODS: Protective effects of verapamil, nifedipine, diltiazem,
      and ethylene glycol tetraacetic acid (EGTA) on acute bromobenzene (BB) toxicity
      to rat hepatocytes were evaluated, and cytosolic [Ca2+]i was monitored in single
      BB-exposed rat hepatocytes. Additionally, the effect of nifedipine on
      phenylephrine-stimulated calcium oscillations was investigated. RESULTS: BB at
      0.8-2.4 mM increased the lactate dehydrogenase (LDH) leakage rate dose
      dependently. Pretreatment with verapamil (25-35 microM), nifedipine (35-45
      microM), diltiazem (25 microM), or EGTA (1.5-5 mM) markedly attenuated the BB
      induced (1.6 mM) LDH leakage rate during 2 h of incubations. BB did not cause any
      detectable acute change in [Ca2+]i. BB interfered with phenylephrine-stimulated
      calcium oscillations, by blocking the oscillations in 58% of the cells and
      reducing the oscillation frequency in the rest. Nifedipine (100 and 200 microM)
      blocked the phenylephrine-induced calcium oscillations completely in 55% and 88%
      of the cells, respectively. CONCLUSIONS: The findings demonstrate that verapamil,
      nifedipine, diltiazem, and EGTA significantly protect rat hepatocytes against BB
      toxicity. BB interferes with phenylephrine-stimulated calcium oscillations.
      Nifedipine inhibits the oscillations at doses higher than those exerting a
      protective effect.

PMID- 7569770
TI  - Response to an extra dose of hepatitis B vaccine and specific antibody
      persistence in non-responders to primary immunization.
AB  - BACKGROUND: In a campaign to vaccinate health care workers, a three-dose schedule
      (0, 1, and 6 months) and a four-dose schedule (0, 1, 2, and 14 months) with
      hepatitis B (HB) vaccine were used. After primary immunization 26 subjects
      vaccinated with the 3-dose schedule and 4 subjects vaccinated with the 4-dose
      schedule had undetectable anti-HBs titres. METHODS: All these 30 non-responders
      received an extra dose of the same vaccine 2 months after primary immunization
      and a booster dose with a yeast-derived vaccine 6 years later. Anti-HBs levels
      were evaluated 1 month after the extra dose and after the booster dose. RESULTS:
      One month after the extra dose 26.9% (7 of 26) of the subjects vaccinated with
      the 3-dose schedule became positive for anti-HBs. Six years later only two of
      these subjects had detectable anti-HBs. After the booster dose the seven subjects
      who responded to the extra dose showed an anamnestic type of response, and five
      additional subjects became positive for anti-HBs. Responders to the extra dose
      were significantly younger than the non-responders. In the four-dose group only
      one subject responded to the extra dose, and that subject maintained protective
      anti-HBs. CONCLUSION: About 25% of non-responders to primary HB vaccination could
      benefit from an extra dose, and these subjects show an anamnestic type of
      response to HBs antigen even after 6 years. This response seems to be influenced
      by age.

PMID- 7569771
TI  - Signet ring cell carcinoma in hyperplastic polyp.
AB  - BACKGROUND: A polypectomy was performed on a 68-year-old woman who had three
      gastric hyperplastic polyps. A focal signet ring cell carcinoma was discovered in
      one of the polyps, which was 2.2 cm in diameter and was located in the antrum.
      METHODS: To study the carcinoma's phenotype expression, special mucin
      histochemical stainings were performed. RESULTS: The carcinoma infiltrated only
      into the mucosa. Intestinal metaplasia was scant. In the neoplasm neutral and
      foveolar mucin was predominant over acid mucin. The surrounding hyperplastic
      foveolar epithelium showed positivity for neutral mucin, and the intestinal
      metaplasia foci for acid mucin. CONCLUSIONS: This neoplasm has a mixed
      composition of mucins and shares histochemical characteristics with the
      surrounding hyperplastic foveolar epithelium.

PMID- 7569772
TI  - Normal human cord blood B cells can produce high affinity IgG antibodies to dsDNA
      that are recognized by cord blood-derived anti-idiotypic antibodies.
AB  - It is possible to identify, in Epstein-Barr virus-transformed normal human cord
      blood B cell populations, cells present at a low frequency that produce IgG
      antibodies specific for dsDNA. By cloning out these B cells as immortalized
      monoclonal cell lines, it could be shown that the antibodies were the products of
      CD5 positive B cells. Two monoclonal anti-dsDNA antibodies were derived from cell
      lines T52 and A7 and these were further characterized as anionic (pI
      approximately 6.4) IgG4 kappa antibodies that bound with affinities of 7.18 x
      10(9) l/mol and 3.28 x 10(9) l/mol, respectively, to dsDNA but did not bind to
      ssDNA. These affinities were similar to those of polyclonal IgG anti-dsDNA
      antibodies from lupus patients, which ranged from 1 x 10(9) -8.9 x 10(10) l/mol.
      Both T52 and A7 monoclonal anti-dsDNA antibodies were recognized by cord blood
      derived IgM antibodies. These IgM antibodies were not rheumatoid factors but
      bound to the F(ab')2 of A7 and T52 while failing to recognize T50, which is an
      autologous IgG4 kappa monoclonal antibody without specificity for dsDNA. A cloned
      B cell line A24 generated from the same cord blood sample as A7 produced an IgM
      monoclonal antibody that bound to the heavy chains of T52 and A7, but not T50 on
      Western blot and inhibited the binding of these antibodies to dsDNA. A7 and T52
      competitively inhibited each other in their binding to the anti-idiotype A24, and
      A24 inhibited the binding to dsDNA of some polyclonal IgG anti-dsDNA antibodies
      purified from sera of lupus patients. The level of inhibition of binding of these
      antibodies to dsDNA was directly proportional to the levels of expression of the
      idiotype recognized by A24 on these antibodies. The normal human cord blood,
      therefore, may contain cells that form an idiotype/anti-idiotype network in which
      the idiotype is expressed on IgG antibodies with specificity for dsDNA and the
      anti-idiotype is an IgM antibody that binds to a heavy chain idiotope in such a
      way as to interfere with its interaction with dsDNA. The presence of a similar
      idiotype on some polyclonal anti-dsDNA antibodies in lupus that are similarly
      inhibitable by the cord blood-derived anti-idiotype raises the possibility that
      this network may persist in later life and perhaps become dysfunctional in
      systemic lupus erythematosus.

PMID- 7569773
TI  - Modulation of antigen-antibody complexations by immunoglobulins.
AB  - In this investigation, the modulating effects of non-immune human IgG and
      rheumatoid factors (RFs) on antigen-antibody complexations were studied. Non
      immune human IgG, as well as RF, were found to inhibit the binding of antigen to
      specific antibodies of both human and rabbit origin. In addition, human
      immunoglobulins were also able to modify the composition of preformed antigen
      antibody complexes. The effects were detected by immunological methods in two
      different antigen-antibody systems (human serum albumin-rabbit anti-HSA and
      tetanus toxoid-human anti-TT). Changes in biological activities could be followed
      by employing enzymes (glucose-6-phosphate dehydrogenase and human placental
      alkaline phosphatase) as antigens. The outcome of the effects was found to be
      dependent on the ratio of antigen to antibody, the antigen-binding properties of
      the antibody and its origin, and on the properties of the immunoglobulins added.
      The observed changes could not be explained only by the presence of specific
      antibodies in the immunoglobulin preparations. The ability of immunoglobulins to
      modulate antigen-antibody complexations may provide a rationale for the large
      amounts of non-specific immunoglobulins in the circulation by preventing
      premature precipitation and promoting the elimination of antigenic molecules.

PMID- 7569774
TI  - Metalloproteases and serineproteases are involved in the cleavage of the two
      tumour necrosis factor (TNF) receptors to soluble forms in the myeloid cell lines
      U-937 and THP-1.
AB  - The proteolytic processing of the two TNF receptors (TNF-R55 and TNF-R75) into
      soluble forms was investigated in the myeloid cell lines U-937 and THP-1. Phorbol
      myristate acetate (PMA) rapidly stimulated release of soluble forms of both TNF
      receptors. Incubations were made with PMA and protease inhibitors directed
      against different target protease groups. The serineprotease inhibitors TPCK and
      dichloroisocoumarin and the metalloprotease inhibitor 1,10-phenanthroline reduced
      PMA-induced release of both soluble receptor forms with about 60-70%.
      Furthermore, 1,10-phenanthroline also reduced PMA-induced down-regulation of TNF
      receptors in both cell lines as judged by TNF-binding to cells. Reduced down
      regulation and TNF-receptor shedding by 1,10-phenanthroline was reversed by Zn2+,
      indicating involvement of a Zn(2+)-dependent metalloprotease. Thus, both serine
      proteases and metalloproteases are involved in the processing of TNF-receptors.

PMID- 7569775
TI  - Binding to erythrocyte complement receptor type 1 of BSA/anti-BSA complexes
      opsonized by C4A3 or C4B1 in the presence of serum.
AB  - An in vitro model with human serum and human 0 Rh-negative erythrocytes was used
      for studies on preformed BSA/anti-BSA complex binding to complement receptor type
      1 (CR1). The serum used was first depleted of Clq, factor D and properdin, then
      of C3, C4 or both and finally reconstituted with the desired proteins (serum
      reagent). With varying C4 concentrations and 100% C3 present, binding curves
      obtained for the two C4 isotypes were similar. When the serum reagent was not
      reconstituted with factor D and properdin there was no difference between the CR1
      binding of normal serum and the partially reconstituted serum reagent, nor
      between the two C4 isotypes in this serum reagent. When C3 at 50% or 100% of
      normal concentrations was added to the serum reagent together with 100% C4A3 or
      C4B1, the C4B1-opsonized complexes showed more binding than the C4A3-opsonized
      complexes. At very low levels of C3 (< 25%) the binding could not be
      distinguished from the background. The results suggest that the binding of
      complement opsonized antigen/antibody complexes to erythrocyte CR1 is mediated
      mainly by C3, originating from activation of the classical pathway, and that the
      difference in properties between C4A and C4B does not have a major influence.

PMID- 7569776
TI  - Allosteric and temperature effects on the plasma protein binding by streptococcal
      M protein family members.
AB  - Most group A streptococcal strains bind immunoglobulins (Ig) and fibrinogen to
      their cell walls. It is shown in this paper that the Ig-binding of three
      different strains was much weaker at 37 degrees C than at room temperature (20
      degrees C), whereas the fibrinogen binding was unaffected by temperature. The
      binding properties and molecular sizes of two purified group A streptococcal cell
      surface proteins from the M protein family were studied at various temperatures,
      M1 protein with affinity for IgG, fibrinogen and albumin, and protein Sir22 with
      affinity for IgA and IgG. Both proteins appeared as monomers which bound all
      their ligands, including fibrinogen, very weakly at 37 degrees C, and as strongly
      binding dimers at 10 and 20 degrees C. Furthermore, the results demonstrated that
      the plasma protein binding of the bacterial proteins was allosterically
      regulated, i.e. the binding of a ligand to one site modulated the binding of a
      ligand to a second site. For example, the binding of albumin or IgG to purified
      M1 protein at 10 and 20 degrees C strongly enhanced the binding of fibrinogen at
      37 degrees C. This indicates that the high affinity dimer form of the bacterial
      proteins can be stabilized at 37 degrees C, a possible explanation for the strong
      fibrinogen binding of whole bacteria. Finally, the sizes and binding properties
      of three M1 protein fragments were studied and the results indicated that the
      centrally located C-repeats, which are conserved among the members of the M
      protein family, are important for the formation of the high-affinity dimers of
      the bacterial proteins.

PMID- 7569777
TI  - V-region and class specific RT-PCR amplification of human immunoglobulin heavy
      and light chain genes from B-cell lines.
AB  - We have designed and tested primers that amplify complete human kappa and lambda
      light chain genes, and human Fd fragments from gamma, mu and alpha heavy chain
      genes. These primers were tested for efficiency and specificity on monoclonal
      sources of human immunoglobulin RNA, obtained from human B-cell lines of known
      immunoglobulin gene expression. Analysis of the sequences derived from these B
      cells confirms the specificity of the PCR primers and the extent of somatic
      mutation seen in different B-cell malignancies supports existing concepts for
      differing aetiologies in the tumours concerned.

PMID- 7569778
TI  - T-cell receptor J beta gene segment usage in immature and mature human
      thymocytes.
AB  - Immature double positive (DP, CD4+CD8+) and mature single positive (SP, CD4+CD8-
      and CD4-CD8+) human thymocytes from nine thymi were analysed for their complete
      patterns of relative TCR J beta multigene member usage in relation to six
      rearranged V beta family exons (V beta 5.1, 6.1-3, 8, 9, 12 and 18). Each sample
      tested contained mRNA transcripts corresponding to all potential V beta(D beta)J
      beta combinations. Individual J beta gene segments were expressed in a similar,
      highly non-random manner both in SP and DP thymocytes, irrespective of original
      genomic position of the individual associated V beta exon. In addition, ranges of
      family usage and frequency of individual over-representations of J beta gene
      segments, as determined in DP and SP thymocyte populations, displayed no
      significant differences. Upon comparison of DP and SP thymocytes, however, a
      discrepancy in one aspect of J beta gene utilization was established: decreasing
      J beta family 1/J beta family 2 ratios were determined to be positively
      correlated with increasing maturity of thymocytes, a condition further supported
      by data previously obtained from studies of PBL T cells. At the individual J beta
      gene level, the observed gradual modification of the relative family usage can
      largely be explained by a significant shift from a higher J beta 1.1/J beta 2.7
      ratio in DP to a higher J beta 2.7/J beta 1.1 ratio in SP thymocytes. Altogether,
      the present results imply that selectional processes in the thymus appear to have
      only minor consequences on the distribution pattern of expressed J beta exons.
      Hence, the disproportionate pattern of TCR J beta gene usage seems to be
      established mainly at the recombinatorial level followed by minor adjustments
      during thymic and post-thymic events.

PMID- 7569779
TI  - Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is
      associated with decreased IFN-gamma and IL-4.
AB  - CD8+ T cells can perform both Th1- and Th2-like functions by producing cytokines
      such as interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), as well as the
      immune response down-regulating transforming growth factor-beta (TGF-beta), which
      are all involved in the development of experimental autoimmune myasthenia gravis
      (EAMG), a model for human MG. We have reported that depletion of CD8+ T cells
      results in the suppression of EAMG accompanied by the down-regulation of AChR
      specific B cell responses and AChR-reactive IFN-gamma secreting Th1-like cells.
      To identify the involvement of IFN-gamma, IL-4 and TGF-beta in the development of
      EAMG after CD8+ T cell depletion, the expression of mRNA for these cytokines was
      studied in mononuclear cells from popliteal, inguinal and mesenteric lymph nodes,
      spleen and thymus by adopting in situ hybridization with complementary DNA
      oligonucleotide probes. Depletion of CD8+ T cells resulted in decreased levels of
      IFN-gamma and IL-4 mRNA expressing cells in different lymphoid organs except
      thymus, but no change in the numbers of TGF-beta mRNA expressing cells. The
      results imply that the suppression of EAMG after depletion of CD8+ T cells is
      caused by decreasing the effector factors but not by increasing the suppressor
      factor(s).

PMID- 7569780
TI  - Dysregulation of T helper cell cytokines in autoimmune prone NZB x NZW F1 mice.
AB  - Multifactorial involvement in the pathogenesis of autoimmune NZB/W F1 mice has
      been well documented. To further elucidate the role of cytokines in the disease
      development of murine lupus, single spleen cells isolated from NZB/W F1 and non
      autoimmune C57BL/6 mice were stimulated with T cell mitogens or anti-CD3 antibody
      at pre-determined optimal concentration. Supernatants were collected and assayed
      for production of cytokines including IL-2, gamma-IFN, IL-3, IL-4, IL-5 and IL
      10. In both young and old mice, cytokine profiles by mitogen-stimulated T cells
      showed higher TH2 (type 2 T helper) cell-related cytokine production in NZB/W F1
      mice compared to those in non-autoimmune C57BL/6 mice. In contrast, cytokines
      produced by TH1 (type 1 T helper) cells, such as gamma-IFN and IL-2, were lower
      in NZB/W F1 mice by stimulation with either mitogen or anti-CD3 antibody. In
      addition, cytokine production at different time points also demonstrated
      decreased gamma-IFN and increased IL-4 levels by anti-CD3 stimulated splenic
      cells in autoimmune NZB/W F1 mice. Furthermore, the IL-10 levels produced by
      lipopolysaccharide (LPS)-stimulated splenic and peritoneal exudate cells were
      higher in young NZB/W F1 mice compared to those in C57BL/6 mice. Our data suggest
      that dysregulation between TH1 and TH2 cells may play an important role in the
      pathogenesis of autoimmunity in NZB/W F1 mice.

PMID- 7569783
TI  - Secretion of MPB64 antigen by a recombinant clone of Mycobacterium smegmatis:
      characterization and application for the diagnosis of tuberculosis.
AB  - MPB64, a specific antigen to Mycobacterium tuberculosis complex (TB complex), was
      produced and secreted by a clone of M. smegmatis-MPB64 where the structural gene
      of MPB64 was inserted using a new mycobacteria, E. coli shuttle plasmid pNIS
      vector. Antibodies against the recombinant MPB64 (rMPB64) were used for the
      reverse particle latex agglutination (RPLA) test to detect the MPB64 antigen
      rapidly. RPLA tests were applied to the shock cultures and the clinical isolates
      of mycobacteria to identify TB complex. RPLA with anti-MPB64 antibody-coated
      latex beads completely distinguished TB complex from other mycobacteria. Thus, it
      is suggested that RPLA with anti-MPB64 antibody would be a new, easy and
      inexpensive method for the rapid diagnosis of tuberculosis.

PMID- 7569781
TI  - Usage of beta 1 integrin ligands by B cells is developmentally regulated in avian
      bursa.
AB  - Chicken B cell development takes place in a separate organ, the bursa of
      Fabricius, which provides the blood-borne stem cells, a microenvironment
      specialized for B cell maturation. Therefore, chicken can be used as a model to
      study specifically the molecules and interactions which control the development
      of the B cell compartment. In this work, we studied expression, localization and
      function of beta 1 integrins on maturing B cells and bursal stroma. The
      expression of beta 1 integrins on B cells increases during the embryonic
      development and beta 1 integrin-positive cells can be found both in the medulla
      and the cortex throughout the bursal development. The binding assays show that
      the attachment of B cells to stroma is mediated by beta 1 integrins. Binding to
      10-day-old embryonic stroma is fibronectin-independent, whereas fibronectin
      mediated binding takes place in an increasing manner during further embryonic
      maturation. After hatching fibronectin appears to be the main binding site for B
      cells. However, the epitope of beta 1 integrin which takes part in the adhesion
      of B cells to stroma and to fibronectin is not crucial for the homing of cells
      into the bursa in a cell transfer model. Our results indicate that the
      interaction of beta 1 integrins with their ligands is developmentally regulated
      in the bursa and suggest that B cell maturation may be partially controlled by
      this interaction.

PMID- 7569784
TI  - Immunophenotypic and functional characteristics of haemopoietic cells from human
      cord blood.
AB  - Cord blood (CB) as a new source for bone marrow transplantation represents
      advantageous features concerning stem cell and leucocyte compartments and
      function. We attempted to get more information about the phenotypes and function
      of CB cells by investigating their cell surface markers and also the production
      of IL-2, IFN-gamma and IL-6 by mitogen and alloantigen stimulation. The CB cells
      were characterized by a low proportion of CD3+ T cells, CD4+ T subpopulation,
      activated T cells and CD3+CD16/CD56+ cytotoxic cells, suggesting reduced graft
      versus host potential. The significant increase of CD19/CD3 double positive cells
      and decrease of CD19/HLA-DR double positive mature B cells reflect that immature
      B cells exist in CB. In the functional studies, a 27- and 5-fold reduction was
      observed in the production of IFN-gamma by CB cells stimulated with PHA and
      allogeneic cells, respectively. The production of IL-2 in PHA-stimulated CB cells
      also showed a 50% determination. Decrease in the production of these cytokines by
      CB cells is supported by the decline of the proportion of CD3+ T cells. However,
      an increase was observed in the production of IL-6 by CB cells stimulated with
      allogeneic cells as compared with the controls. These results suggest a
      difference in the functional activity of the T helper cell subsets between the CB
      and peripheral blood and/or differences in the functional maturity of T helper
      cell subsets and B cells in these compartments.

PMID- 7569782
TI  - The neuropeptide substance P does not influence the migration of B, T, CD8+ and
      CD4+ ('naive' and 'memory') lymphocytes from blood to lymph in the normal rat.
AB  - Thoracic duct lymphocytes (TDL) continuously patrol through the body,
      facilitating immune responses at most sites. The neuropeptide Substance P might
      regulate immune responses by influencing the migration of TDL. Therefore, it was
      investigated whether Substance P affects the migration of thoracic duct B, T,
      CD8+ and CD4+ ('naive' and 'memory') lymphocytes from blood to lymph in vivo.
      Labelled TDL were either incubated with Substance P and then injected into normal
      rats, or incubated without Substance P and then injected into rats continuously
      receiving Substance P intravenously. The numbers of labeled B, T, CD8+ and CD4+
      ('naive' and 'memory') lymphocytes were determined in blood and thoracic duct
      lymph for 1 and 5 days, respectively. Neither the in vitro incubation with
      Substance P nor its in vivo application influenced the disappearance of any
      lymphocyte subset from the blood or its reappearance in the lymph. In addition,
      continuous intravenous application of the Substance P antagonist CP 96.345 did
      not alter the volume or the lymphocyte number of the efferent lymph. The present
      study indicates that the nervous system does not influence immune responses via
      Substance P by altering the migration pattern of B, T, CD8+ and CD4+ ('naive' and
      'memory') lymphocytes.

PMID- 7569785
TI  - Functional analysis of a new polymorphism in the human TNF alpha gene promoter.
AB  - In this paper the functional relevance of a TNFA promoter polymorphism, a G/A
      polymorphic sequence at position -238, was tested by analysing its influence on
      TNF alpha production upon in vitro stimulation of monocytes from 78 healthy,
      unrelated individuals by lipopolysaccharide (LPS) or after allogenic stimulation
      in a panel of 32 healthy individuals. All TNFA-A positive individuals were either
      DR3 or DR7 positive, confirming the previously reported strong linkage
      disequilibrium of the TNFA-A allele with the two extended haplotypes (B18, F1C30,
      DR3) and (B57, SC61, DR7). No individuals homozygous for the TNFA-A allele were
      present in the panel. The mean level of TNF alpha production was not
      significantly different in TNFA-G/G homozygous and in TNFA-A/G heterozygous
      individuals after LPS stimulation of monocytes (P = 0.35) or after allogenic
      stimulation (P = 0.7). After LPS and allogenic stimulation DR3 positive
      individuals had a higher mean TNF production. This could not be further
      differentiated by typing for TNF -283.

PMID- 7569786
TI  - The upper arm arterio-venous fistula--an alternative for vascular access in
      haemodialysis.
AB  - Forty-eight consecutive arteriovenous fistulae of the upper arm constructed in 44
      patients between 1983 and 1987 were reviewed. The median observation time was 8.5
      months (range 1 day-65 months). The overall patency rate for fistulae used for
      haemodialysis (early failures excluded) was 50% after one year and 38% after two
      years. However, only six (18.7%) of the used fistulae stopped because of
      thrombosis. The total number of thromboses was nine (19.6%). The main cause of
      discontinuance of fistulae was a high number of deaths (n = 22), presumably a
      result of a high median age of 62 years. Early failure rate was seven of 46
      (15.2%); in three cases (6.5%) this was caused by thrombosis. The results are
      compared to other alternatives for radiocephalic fistulae and the difficulties of
      comparisons are discussed. It is concluded that the upper arm arteriovenous
      fistula can serve as a second choice, when a radio-cephalic fistula fails.

PMID- 7569787
TI  - Intensified dialysis treatment of ethylene glycol intoxication.
AB  - During a period of 10 years 18 men were treated for severe ethylene glycol (EG)
      intoxication. All patients received supportive measures and ethanol infusion.
      Hemodialysis (HD) was applied in 11 patients (Group I) whereas 7 patients, who
      exhibited more advanced toxicity symptoms, received peritoneal dialysis (PD)
      simultaneously with HD (Group II). Patients in Group II showed more advanced
      acidosis on admission than in Group I (Base excess -27.1 mmol/l versus -16.8
      mmol/l, p < 0.0075). The results of treatment in these two groups of patients
      were compared. All patients in Group I survived and one patient in Group II died.
      The patients in Group II were discharged with higher serum creatinine and follow
      up time to improve renal function was longer than in Group I (252 versus 149
      mumol/l, p < 0.015 and 23 versus 7.9 weeks, p < 0.05 respectively). No
      correlations were found between serum EG and grade of acidosis on admission or
      serum EG and subsequent increase of serum creatinine but acidosis on admission
      was highly correlated to the rise of serum creatinine after the 72 hours of
      observation time (p < 0.0001). It is concluded, that combined HD and PD treatment
      was beneficial in the presented patients as it corrected acidosis earlier and
      could eliminate EG and its toxic metabolites faster, improving prognosis.

PMID- 7569788
TI  - Plasma pentosidine levels in uremic patients before and after hemodialysis.
AB  - Pentosidine, a fluorescent cross-link, is one of the advanced glycosylation end
      products. It accumulates in human tissues, plasma and urine in diabetic and
      uremic patients. Using SP-Sephadex C-25 in the pretreatment for reversed-phase
      HPLC, we determined pentosidine levels in plasma before and after hemodialysis
      using cuprophane membranes from 18 patients (9 diabetic, 9 nondiabetic) with end
      stage renal disease, as well as examined the hemodialysis efficiency of plasma
      pentosidine. We also measured beta 2-microglobulin levels in plasma before and
      after hemodialysis. The values of plasma pentosidine did not significantly change
      after hemodialysis. Also, plasma beta 2-microglobulin was not removed by
      hemodialysis. Hemodialysis efficiency of plasma pentosidine and beta 2
      microglobulin was nil. In addition, there was a significant correlation between
      plasma levels of pentosidine and beta 2-microglobulin before hemodialysis in 116
      uremic patients. The results indicated that hemodialysis could not eliminate
      pentosidine from plasma; therefore, pentosidine retention by the diseased kidney
      might be a major cause of elevated levels of pentosidine with uremia.

PMID- 7569789
TI  - Measurement of glomerular filtration rate by single-injection, single-sample
      techniques, using 51Cr-EDTA or iohexol.
AB  - Clearance calculations based on single sample determinations from 51Cr-EDTA
      samples 180 min after giving radioisotope showed a correlation coefficient of
      0.992 to clearance calculations after multiple sampling of 51Cr-EDTA. The range
      of clearance determinations in 108 patients varied from 4 to 141 ml/min, 1.73 m2
      BA. Twenty patients had clearance values below 20 ml/min, 1.73 m2 BA. Clearance
      calculations from single samples of iohexol from 180 min values showed a
      correlation coefficient of 0.986 to clearance calculations after multiple
      sampling of 51Cr-EDTA. These calculations were based on samples from 122 patients
      with clearance values varying from 4 to 139 ml/min, 1.73 m2 BA. No adverse
      reactions were registered during the study. This study confirms the reliability
      of single sample methods for clearance calculations at all levels of renal
      function.

PMID- 7569791
TI  - Antioxidants attenuate endotoxin-gentamicin induced acute renal failure in rats.
AB  - The synergistic mechanism by which endotoxin enhances the nephrotoxic potential
      of gentamicin is unknown. In this study, we attempted to shed light on this
      mechanism by injecting rats with endotoxin plus gentamicin. Renal injury was
      assessed by measuring creatinine, inulin and PAH clearance, NADH levels and
      electrolyte reabsorption, for 24 hr following this injection. Gentamicin alone
      (20 mg/100 g) induced no renal injury, while endotoxin without gentamicin (0.075
      mg/100 g) induced mild injury. However, endotoxin plus gentamicin resulted in
      acute renal failure. In an attempt to halt the progressive renal dysfunction, the
      antioxidants NAO (5 mg/100 g), Vitamin E (0.2 mg/100 g per day) and
      dimethylthiourea (DMTU-50 mg/100 g) were administered, or early endotoxin
      tolerance was induced before injecting the rats with endotoxin plus gentamicin.
      The reduction in renal function was markedly slower in rats administered with
      antioxidants compared with untreated rats. Similar results were obtained with
      endotoxin tolerance. These data suggest that NAO, vitamin E, DMTU and endotoxin
      tolerance are potentially beneficial in arresting progressive renal damage
      associated with endotoxin plus gentamicin.

PMID- 7569792
TI  - Painless ESWL by cutaneous application of vaseline.
AB  - In a prospective study we investigated the efficacy of cutaneous vaseline
      application in pain reduction during ESWL. In 150 patients (group 1) vaseline was
      applied on a skin area of 10 x 20 cm corresponding to the entry site of shock
      waves directly before ESWL was started. In 75 patients (group 2) ESWL was
      performed without vaseline. 10/150 (6.7%) in group 1 and 27/75 (36.4%) in group 2
      (p < 0.001) needed additional analgesic sedation. Requirement for supplementary
      analgosedation was most pronounced for patients with lower calyceal and distal
      ureteral stones [20% and 19% in group 1; 53% and 78% in group 2 (p < 0.03)]. The
      median pain score in group 1 was 2.5 +/- 1.05, in group 2 4.25 +/- 1.13 (p <
      0.05). Local vaseline application significantly reduced pain during ESWL
      independent from stone location. Because of its high viscosity vaseline inhibited
      the development of cavitation bubbles at the skin surface. Cutaneous vaseline
      application reducing the need for analgesic sedation might especially be useful
      in outpatient ESWL procedures.

PMID- 7569790
TI  - Tamm-Horsfall protein in reflux nephropathy.
AB  - The distribution of Tamm-Horsfall protein, the main protein in normal urine, was
      studied immunohistologically in the kidneys of 70 pigs with unilateral vesico
      ureteric reflux but without outflow obstruction. Strains of Escherichia coli were
      inoculated in the bladder. Inflammatory changes of reflux nephropathy (chronic
      pyelonephritis) were found in 52 pigs. There were extra-tubular deposits of Tamm
      Horsfall protein in the kidneys of only 26 pigs. These deposits were small,
      increased in prevalence as the size of inflamed areas increased, and were not
      associated with deposits of the protein in glomeruli. These findings suggest that
      escape of Tamm-Horsfall protein from tubules and backwash into glomeruli are not
      major features of low pressure reflux nephropathy, unlike the findings in outflow
      obstruction of the lower urinary tract. There was no evidence that a reaction to
      Tamm-Horsfall protein was important in the pathogenesis of reflux nephropathy.

PMID- 7569793
TI  - Estrogen receptors in the human male bladder, prostatic urethra, and prostate. An
      immunohistochemical and biochemical study.
AB  - The distribution and quantity of estrogen receptors (ERs) in the human male
      bladder, prostatic urethra and the prostate were studied in eight males with
      recurrent papillomas of the bladder or monosymptomatic hematuria (median age 61
      years), 14 men undergoing transurethral resection due to benign prostatic
      hyperplasia (median age 70 years), and nine men undergoing cystectomy due to
      malignant tumour of the bladder (median age 70 years). In the first group of
      patients, biopsies for immunohistochemical examination were obtained from the
      bladder vault, bottom, both side-walls, the trigone area, and the mid-portion of
      the prostatic urethra, and in the second group from three locations of the
      prostatic urethra (bladder neck, mid-portion and veramontanum). In the third
      group, tissue specimens were taken from the vault of the bladder, prostatic
      urethra, and the prostate, for immunohistochemical as well as biochemical
      analysis. In the first group, ERs were found in three out of eight specimens of
      the prostatic urethra, and in one of these, ERs were confined to periurethral
      glands. ERs could not be demonstrated in any of the bladder-biopsies. In the
      second group, ERs were not found in the bladder neck, but were seen in four
      preparations from the veramontanum and in two from the midportion of the urethra.
      ERs were located in the urothelium and periurethral glands. In the third group,
      ERs were seen immunohistochemically in the prostatic urethra (two cases) and the
      prostatic stromal tissue (two cases). ERs could be demonstrated in the bladder
      neither by immunohistochemistry nor biochemically.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7569794
TI  - Voiding dysfunction and urodynamic findings in patients with lumbar spinal
      stenosis and the effect of decompressive laminectomy.
AB  - Eighteen consecutive patients (12 men and 6 women, mean age 55) with clinically
      and radiologically verified lumbar spinal stenosis underwent urodynamic
      examinations before decompressive laminectomy (n = 16) and 15 afterwards. Twelve
      of the patients (67%) had symptoms of voiding dysfunction preoperatively but
      urodynamic findings were normal in most cases only one patient showing detrusor
      hyperreflexia and one obstruction. Three patients reported an improvement in
      voiding postoperatively. Three patients showed obstructive voiding
      postoperatively, one undergoing TURP with a good outcome. One patient developed
      detrusor areflexia after the operation, with difficulties in bladder emptying.
      The only statistically significant changes in urodynamic parameters were rises in
      the maximum urethral pressure and urethral closure pressure. When considering the
      radicular symptoms and back pains the overall outcome was assessed as excellent
      or good in 6 cases, 6 had a fair outcome and 4 poor. Decompressive laminectomy
      gives acceptable results but the effects on bladder and urethral function remain
      controversial and unexpected. Electrophysiological investigations are needed for
      more detailed analysis of these cases.

PMID- 7569795
TI  - Pre treatment decision making in prostatism--a stochastic analysis based on the
      most used diagnostic tests.
AB  - In order to estimate the probabilities that a patient would belong to subgroups
      created by the diagnostic tests most used by European urologists four hundred and
      twenty-one consecutively referred prostatism patients were studied. It was
      demonstrated that all the qualities described by these tests were distributed in
      such a way that the presumed accuracy of the tests might result in a 20 per cent
      variance in the number of treated patients. A simple self administered home flow
      test, which was significantly correlated to the maximum flow rate, was shown to
      be stronger correlated to the symptoms of the patients compared to any other
      quality. A stochastic table for prostatism was constructed, which may be used for
      estimations of the influence different decision making may have on the outcome of
      treatments in this kind of patients.

PMID- 7569796
TI  - Responders and non-responders to treatment of benign prostatic hyperplasia with
      transurethral microwave thermotherapy.
AB  - One hundred and seventy two patients with benign prostatic hyperplasia (BPH) were
      treated with transurethral microwave thermotherapy (TUMT) using Prostcare (Bruker
      Spectrospin). The treatment was performed with an effect of 52 W and a frequency
      of 915 MHz, which was generally well tolerated and no serious side effects were
      observed. In the majority of the patients there was an improvement of subjective
      symptoms with a significant decrease in Madsen and bothering scores after
      treatment. In the total patient group, Qmax and voided urine volume were
      increased slightly, but not statistically significantly. The patients were
      divided in responders and non-responders, based on Madsen symptom score after 3
      months or if complementary treatments were necessary during the follow up period
      of one year. No significant differences between the groups were observed
      regarding pretreatment variables except that patients in the responder group
      experienced the treatment more painful than non-responders. Qmax in the responder
      group was significantly improved at 6 and 12 months follow up. PSA levels
      increased significantly after the treatment. Routine evaluation using flow rate,
      estimation of prostatic size, measurement of residual urine volume and cystoscopy
      does not give sufficient information for predicting treatment outcome.

PMID- 7569797
TI  - Bacteriologic, histologic and ultrasonographic findings in strictures recurring
      after urethrotomy. A preliminary study.
AB  - Twelve men with recurrent anterior urethral stricture after endoscopic
      urethrotomy (2-12 attempts) underwent open urethroplasty with en bloc removal of
      diseased urethral segments. Bacteriologic and histologic studies of the excised
      urethral tracts (mucosa and spongiosum tissue) were performed. The bacteriologic
      findings were compared with the results of preoperative urine cultures and
      urethral swabs for chlamydia. The histologic findings were related to
      preoperative ultrasonographic observations, in order to evaluate the accuracy of
      ultrasonography in depicting structural changes in spongiosum around the
      strictured urethral tract. Beta-haemolytic streptococci and Streptococcus
      faecalis were cultured from the excised spongiosum, without correlation to the
      preoperative culture results. The histologic studies confirmed the usefulness of
      urethral ultrasonography for accurate demonstration of the inflammatory changes
      involving spongiosum around the strictures.

PMID- 7569798
TI  - Microsurgical correction of posttesticular obstruction. Peroperative findings and
      postoperative semen quality.
AB  - Exploration for microsurgical reconstruction of the vas deferens or its
      epididymal junction was performed in 47 consecutively treated men.
      Epididymovasostomy was planned in 27 cases. Malformation was found in five and
      Young's syndrome in nine, and most of the others had a history of urogenital
      infections. Reconstruction was accomplished in 17 cases. Nine were azoospermic
      preoperatively. Four (three with Young's syndrome/malformation) remained so,
      whereas patency was demonstrated in four and one did not supply a semen specimen
      postoperatively. Eight had severe unexplained oligozoospermia preoperatively, and
      in four of them the sperm counts normalized postoperatively while the other four
      remained oligozoospermic. In no case did preoperative oligozoospermia progress to
      azoospermia postoperatively. Complete normalization of all spermiogram parameters
      occurred in only two cases after epididymovasostomy. Of the 20 who underwent
      reversal of vasectomy, 17 provided semen for postoperative testing. 16/17
      specimens contained spermatozoa, but spermiograms, including penetration tests,
      were completely normal in only three cases. This study indicates a discrepancy
      between good patency and good semen quality. Our study also suggests that some
      men with unexplained severe oligozoospermia are as likely to benefit from
      epididymovasostomy as are azoospermic men.

PMID- 7569799
TI  - Anatomic comparison of the ipsilateral and the contralateral testis in
      intravaginal torsion.
AB  - Sixteen cases of intravaginal testicular torsion were studied to compare the
      intrascrotal anatomy with that of the contralateral testis and to determine
      possible anatomic predisposition to testicular torsion. The anatomy of the
      contralateral testis was not always similar to that of the ipsilateral testis,
      and four of the contralateral testes were judged to be without risk of torsion.

PMID- 7569800
TI  - Secondary oxalosis of bone in a dialysis patient.
AB  - Secondary oxalosis of bone is a complication of chronic renal failure. Its
      frequency and the mechanism of the deposition is unknown. We report the case of
      chronic renal failure patient on hemodialysis with deposition of oxalate in bone.
      Possible mechanisms and the significance of the depositions is also discussed.

PMID- 7569802
TI  - Transitional cell carcinoma of residual kidney after partial nephrectomy for
      renal adenocarcinoma.
AB  - Transitional cell carcinoma of the superior calyces was found 1 year after
      ipsilateral partial nephrectomy for renal adenocarcinoma. The main special
      features of the case are the rare occurrence of two primary tumours in the same
      kidney and the previous conservative surgery. A review of the literature has
      revealed no earlier case of this type.

PMID- 7569801
TI  - Spontaneous regression of brain metastasis secondary to renal cell carcinoma.
AB  - Spontaneous regression of malignant tumors is a rare event. A case involving
      brain metastasis from renal cell carcinoma (RCC) is presented. Nine years after
      the diagnosis of metastasis the patient is alive without evidence of recurrence.
      We have only found three previous RCC cases in the literature involving
      spontaneous regression of brain metastasis (4, 16, 17).

PMID- 7569804
TI  - Multicystic mesothelioma presenting as a pelvic tumour: case report and
      literature review.
AB  - We report the clinical, radiological and pathological findings of a big
      polycystic tumour in the pelvic region which proved to be a multicystic
      mesothelioma affecting the pelvic peritoneum. Clinical and histological
      differential diagnosis are given and a therapy option. Surgical excision for
      localized tumours and debulking for more extensive tumours.

PMID- 7569803
TI  - Bilateral intravesical duplex system ureteroceles with multiple calculi in an
      adult patient.
AB  - We present a case report of an adult female patient with bilateral duplex system
      ureteroceles, containing multiple small stones. There was no history of urinary
      tract infections or stone disease. Treatment consisted of right upper pole
      heminephrectomy because of non-function and transurethral incision of the left
      ureterocele, resulting in almost complete removal of the calculi. Furthermore no
      vesicoureteral reflux was seen 3 months postoperatively. Transurethral incision
      is a safe and effective treatment in removing stones in ureteroceles without
      necessitating further treatment because of vesicoureteral reflux.

PMID- 7569805
TI  - Giant Mullerian duct cyst mimicking prostatic malignancy.
AB  - A giant mullerian duct cyst was initially interpreted as a seminal vesicle cyst.
      Associated prostatic malignancy was suspected because of raised tumour marker
      levels and lysis of pubic bone. Intraoperative vasography gave the correct
      diagnosis. Open partial transvesical excision of the cyst and suprapubic
      prostatectomy were performed. No malignancy was found in the surgical specimens
      and 2 years later the patient remains well.

PMID- 7569806
TI  - True complete diphallia.
AB  - In a case of true complete diphallia, the orthotopic penis was normal in length,
      shape and urethra, whereas the ectopic, perianal, penis had a blind-ending
      urethra, the significant distance between the two making the malformation of an
      extremely rare type. Right renal agenesis and orthopaedic malformations were also
      present.

PMID- 7569807
TI  - Cytogenetics and molecular genetics of human solid tumours.
AB  - It is generally accepted that cancer is a genetic disease resulting from the
      accumulation of multiple genomic rearrangements. These rearrangements involve
      gross chromosomal abnormalities (e.g. translocations and deletions) as well as
      submicroscopic mutations affecting both oncogenes and tumour suppressor genes.
      Recent studies of several tumour specific translocations in sarcomas have shown
      that the translocations result in so-called fusion genes. In this review we will
      discuss the specificity and implications of different genetic alterations in both
      sporadic and hereditary human solid tumours, and provide examples of how these
      changes can be used as tumour specific markers of both diagnostic and prognostic
      significance.

PMID- 7569808
TI  - Increase in length of experimental skin flaps that survive with dibutyryl cyclic
      AMP.
AB  - One of the most important research topics in plastic surgery is the extension of
      the length of skin flaps that survive. We have investigated the increase in the
      length of skin flaps that can be achieved by giving dibutyryl cyclic AMP (DB
      cAMP) to rabbits with experimental skin flaps and compared the results with those
      in animals not given DB-cAMP. Three variables, the arrival of DB-cAMP in the
      critical area of circulation of the flap (n = 6), changes in the blood flow in
      the flap (n = 10), and increase in the length of skin flap that survived (n = 30)
      were investigated by high performance liquid chromatography and laser Doppler
      flowmetry. DB-cAMP reached the critical area of circulation in the skin flap (dye
      distance), increased the blood flow within this area (mean (SEM) peak value 30
      minutes after operation 1.24 (0.06) ml/min/kg compared with 1.06 (0.02) in
      control flaps), and extended the length of the flap that survived (mean (SEM)
      length seven days after operation 66.1 (3.0) mm compared with 60.8 (1.8) mm in
      the control group). We conclude that DB-cAMP improved the blood flow in skin
      flaps in rabbits with a consequent increase in the length of skin flap that
      survived.

PMID- 7569809
TI  - Changes in the spinal terminal pattern of the superficial radial nerve after a
      peripheral nerve injury. An anatomical study in cats.
AB  - The occurrence of changes within the spinal cord over a long period after a
      peripheral nerve injury was investigated in adult cats. The lateral superficial
      branch of the radial nerve was exposed and transsected unilaterally. In one group
      the nerve endings were re-approximated with epineural sutures and in the other
      group the proximal nerve stump was enclosed to prevent regeneration. After a
      survival period of 4-17 months the same nerve on both sides was exposed to an
      intra-axonal nerve tracer, lectin-conjugated horseradish peroxidase, to label the
      nerve terminals within the spinal gray matter by transganglionic transport. The
      general distribution of the terminal field was almost the same after suturing as
      after encapsulation of the transsected nerve, except for a slightly more cranial
      location of the terminal area after suturing compared with the control side. The
      terminal area comprised laminae I-IV of the fifth cervical to the first thoracic
      spinal segment, concentrated towards the sixth to eighth cervical segments. This
      distribution was the same as on the control side, but the experimental and
      control sides differed in intensity of terminals. There was a loss of terminals
      throughout the terminal field in both operated groups, but after nerve suture
      there was some recovery of terminal intensity between 4 and 17 months after the
      injury.

PMID- 7569811
TI  - Observer variation in histological classification of cutaneous malignant
      melanoma.
AB  - To evaluate the variations within and between observers in the interpretation of
      important histological prognostic factors, a series of 96 melanoma patients was
      randomly selected from a database of 1691 patients with cutaneous malignant
      melanoma. The stained sections were examined on two occasions by four experienced
      pathologists. Analysis by observed agreement and kappa statistics showed maximal
      tumour thickness to be the best reproducible variable, with ulceration the second
      best. Regression was the least reproducible, with level of invasion and type of
      melanoma in the mid range. Intra-observer variation was uniformly less than inter
      observer variation for each variable. For tumour thickness a variance component
      analysis was done to quantify the variability further. The clinician should not
      base his choice of treatment entirely on the microscopic classification but take
      into consideration the clinical course and appearance of the tumour.

PMID- 7569810
TI  - Electrophysiological, morphological, and morphometric effects of aging on nerve
      regeneration in rats.
AB  - To investigate the influence of age on the process of nerve regeneration, the
      right common peroneal nerves of 14 2 month old and 14 10 month old rats were
      transected and resutured. At four and eight weeks after the nerve repair, the
      motor nerve conduction velocity (MNCV), latency, and amplitude of the evoked
      potential from the peroneus longus muscle were measured. The number of
      regenerated myelinated fibres, axon diameter, axon area, axon circumference, and
      myelin thickness were also measured. Compared with the control side (left common
      peroneal nerve and muscle), MNCV, latency, and amplitude showed higher recovery
      rates (recovery rate (%) = operated/control x 100) in 2 month old rats than in 10
      month old rats, particularly at four weeks after the operation. In the
      morphometric study, axon diameter, axon area, and myelin thickness also recovered
      more quickly (recovery rate (%) = operated/control x 100) in 2 month old rats,
      particularly four weeks after the operation. Morphologically, myelin remnants
      were not found in 2 month old rats eight weeks after the operation, though they
      remained in 10 month old rats. These studies show that the recovery rate was
      significantly greater in 2 month old rats than in 10 month old rats. The
      explanation seems to be the difference in the speed of Wallerian degeneration,
      axonal regeneration, and myelin regeneration.

PMID- 7569812
TI  - Audit of basal cell carcinoma in Princess Margaret Hospital, Hong Kong:
      usefulness of frozen section examination in surgical treatment.
AB  - A retrospective study was undertaken of 64 Chinese patients with primary
      (previously untreated) basal cell carcinoma (BCC) surgically treated by the
      plastic and reconstructive surgery team at the Princess Margaret Hospital, Hong
      Kong, from January 1988 to March 1994. Sixty-three (98%) were in the head and
      neck region, half on the nose. It was equally common in men (mean age 69 years)
      and women (mean age 67). Two women (3%) were younger than 35. The rate of
      complete excision increased after the introduction of frozen section examination.
      A complete excision rate of 89% (n = 57) was achieved by 1994. We conclude that
      frozen section examination should be done routinely in patients having BCC
      excised.

PMID- 7569813
TI  - Immediate breast reconstruction: short-term experience in 75 consecutive cases.
AB  - Immediate breast reconstructions are being done more often nowadays to avoid the
      stress that the patient experiences while living without a breast. In this paper,
      the procedure and short term outcome of 75 patients who underwent immediate
      breast reconstructions at the Karolinska Hospital are reported. The median age of
      the patients was 48 years, and most of the tumours were stage O to 2 at the time
      of the operation, though reconstructions were also done for patients with more
      advanced cancer, for psychological reasons. The approach was multidisciplinary
      with oncologists, general surgeons, and plastic surgeons involved. Different
      reconstructive methods were used, and the operations were tailor-made for each
      patient. Twenty one permanent prostheses, 11 expanders, 33 expander prostheses,
      and eight pedicled and two free transverse rectus abdominis musculocutaneous
      (TRAM) flaps were used for reconstruction. The opposite breast was adjusted in 43
      (57%) of the patients. There were 11 postoperative complications (15%), and in
      only one patient (1%), could the reconstruction not be completed. There was a
      tendency towards more complicated reconstructive procedures over time. The demand
      for immediate breast reconstruction is steadily increasing from both patients and
      doctors.

PMID- 7569814
TI  - Blood loss during suction-assisted lipectomy with large volumes of dilute
      adrenaline.
AB  - The amount of blood lost during liposuction with the "dry" or classic "wet"
      techniques has been a cause for concern. In the present study 26 consecutive
      patients who underwent syringe-assisted liposuction with the "superwet" or
      "tumescent" technique had their blood loss recorded prospectively. The mean (SD)
      volume aspirated was 2448 (1368) ml and the mean (SD) drop in haemoglobin
      concentration was 11 (7) g/l. The haemoglobin concentration was measured in both
      the fluid and the fat fraction of the aspirate, and the mean (SD) amount of whole
      blood was 16.5 (9.3) ml/litre of aspirate. The present study shows that blood
      loss is considerably reduced when the "super-wet" or "tumescent" technique is
      used, compared with the reported amount lost by authors who used the "dry" or
      classic "wet" techniques.

PMID- 7569815
TI  - Sollerman hand function test. A standardised method and its use in tetraplegic
      patients.
AB  - A standardised hand function test based on seven of the eight most common hand
      grips is reported. The test consists of 20 activities of daily living. The test
      procedure and the method of scoring are described as is our evaluation of the
      validity and reliability of the test. Fifty-nine tetraplegic patients were
      evaluated using the test before reconstructive surgery to their hands. The test
      score correlated well with the accepted international functional classification
      of the patient's arm (r = 0.76, p < 0.001). The mean test score in the arms of
      patients lacking sensation was significantly lower than in those with tactile
      gnosis (O:1-3 compared with OCu:1-3, p < 0.001).

PMID- 7569816
TI  - Microsurgical replantation of partial avulsion of the scalp. Case report.
AB  - An 8-year-old girl was bitten by a dog and, as well as minor wounds, had a
      complete avulsion of the central part of the scalp covering an area of 8 x 10 cm.
      By rotating the replant 180 degrees and by using 5 cm long vein grafts, two
      sleeve anastomoses, and two end-to-end anastomoses the blood supply was restored.
      The operation lasted nine hours, and she stayed in hospital for 12 days. Her
      clinical course was uneventful. At follow-up 23 months later the cosmetic and
      functional results were good.

PMID- 7569819
TI  - Pulsed ultrasound treatment of the painful shoulder a randomized, double-blind,
      placebo-controlled study.
AB  - To study the effect of pulsed ultrasound in shoulder pains, 35 patients were
      treated with pulsed ultrasound and 37 patients with placebo ultrasound in a
      double-blind design. The therapy was given during inpatient rehabilitation, 10-12
      treatments over 3-4 weeks. Treatment time was 10 minutes, frequency 1.0mHz, on
      off ratio 1:4 and intensity 1.0w/cm2. Follow-ups were done after 4-12 months. No
      differences (p < 0.05) in outcomes were found between the groups after the
      treatment period or at follow-ups. These results discourage the adding of pulsed
      ultrasound therapy with the variables used to the conservative treatment of the
      painful shoulder.

PMID- 7569817
TI  - An unusual foreign body in the hand: delayed presentation of an intact human
      tooth. A case report.
AB  - A 44 year old man presented with a painful, swollen right hand 10 days after a
      brawl. A radiography showed an intact human tooth embedded in the soft tissue
      between the metacarpals of the middle and index fingers. The tooth was removed,
      and the wound debrided and left to heal by second intention. He made a complete
      recovery. This case emphasizes the importance of a plain radiography,
      particularly when skin has been breached, and of removal and adequate
      debridement. Our patient was lucky to have had a successful outcome after so long
      a delay in treatment.

PMID- 7569821
TI  - Instrumental activities of daily living related to impairments and functional
      limitations in 70-year-olds and changes between 70 and 76 years of age.
AB  - The aim of this study was to analyse in particular dependence in instrumental
      daily life activities (I-ADLs) and its association with physical impairments and
      functional limitations in the elderly. The study was based on cross-sectional
      data on 70-year-olds (n = 602) and longitudinal data on subjects followed up to
      the age of 76 (n = 371). Persons dependent in ADL had lower values in maximum
      walking speed, grip strength, knee extensor strength, stair climbing capacity and
      in forward reach, compared with those who were independent in ADL. Walking speed
      in both women and men and sight impairment in men had the greatest influence on
      dependence in ADL. Possible critical levels for disability in ADL are discussed,
      as persons who developed dependence between 70 and 76 already had a lower
      capacity in walking speed and knee extensor strength at age 70 than persons who
      retained their independence in ADL.

PMID- 7569820
TI  - Isometric muscle strength and muscular endurance in normal persons aged between
      17 and 70 years.
AB  - Isometric muscle strength was measured in 63 women and 65 men, randomly selected,
      aged 17-70 years, using Penny & Giles' hand-held dynamometer. Eight muscle groups
      as well as the hand grip strength were tested bilaterally. The muscular endurance
      was measured as time to exhaustion in the abductors of the shoulder and the
      flexors of the hip. Reference values for muscle strength and muscular endurance
      are given in the age groups 17-18, 20-29, 30-39, 40-49, 50-59 and 60-70 years of
      age. The mean strength of females was about 65-70% of that of the men, but when
      the results were related to weight, the differences almost disappeared. Both men
      and women seem to have the greatest muscle strength at the age of about 17-18.
      The strength is rather constant up to the age of about 40 years, after which a
      discrete decline is seen up to about 60, from where the decline is more obvious.
      Muscular endurance showed great variability between individuals. However, no
      decrease in endurance was seen in older ages. For both sexes, lower reference
      limits of endurance, with the methods used, for arm abductors are suggested as
      being 3 minutes and for hip flexors, 90 seconds.

PMID- 7569818
TI  - Breast reconstruction--past achievements, current status and future goals.
AB  - Breast cancer is the most common malignant tumour in women, and more than 5000
      new cases are discovered each year in Sweden, this means that one woman in nine
      will be treated for breast cancer during her lifetime. For unknown reasons, the
      incidence increases by 1% each year. Partial mastectomy is the most common
      surgical treatment today, but a large number of women undergo mastectomy--that
      is, excision of all breast tissue including the nipple-areola complex with or
      without an axillary biopsy. Radical mastectomy--that is the Halsted mastectomy
      with excision of the pectoral muscles (51)--is almost never done today, so chest
      wall defects are smaller than in the early days of breast reconstruction. There
      is, however, still a demand from patients for good, natural-looking, and
      longlasting breast reconstructions, and reconstructive surgeons have to search
      for perfection both in existing methods and also in new methods of breast
      reconstruction. The purpose of this article is to review this complex subject.

PMID- 7569823
TI  - Micro- and macrocirculatory, and biohumoral changes after a month of physical
      exercise in patients with intermittent claudication.
AB  - We studied 15 subjects with intermittent claudication, classed as stage II
      according to Leriche-Fontaine. The patients were subjected to laser Doppler
      flowmetry, strain gauge plethysmography, Doppler velocimetry, and blood sampling,
      in basal conditions and after one month of physical training. Symptom-free
      walking distance at the end of the training period showed a significant increase,
      while there was no major change in maximal walking distance or the Windsor index.
      Laser Doppler flowmetry showed no significant change in cutaneous blood flow at
      rest, after the month of physical training. On the other hand, strain gauge
      plethysmography showed a significant decrease in rest flow at the end of the
      training period, while peak flow of postischemic hyperemia did not change
      appreciably. Biohumoral evaluations showed a significant decrease of white blood
      cell count, triglycerides and uric acid. Platelet count, prothrombin time, aPTT
      and plasminogen were unchanged. On the other hand, we recorded a small, but
      significant, rise of fibrinogen. Our study confirmed the importance of scheduled
      physical activity in the patient with intermittent claudication, showing that
      clinical improvement is not accompanied by an increase in the circulatory
      reserve. The unchanged levels of plasminogen suggest that the fibrinolytic
      activity does not vary significantly after a course of physical exercise.

PMID- 7569822
TI  - Physical strength and endurance in relation to perceived psychosocial work
      environment, sleep disturbance and coping strategies in men. Stockholm MUSIC I
      (MUsculo-Skeletal Intervention Centre) Study Group, Stockholm.
AB  - The study explored relationships between subjective descriptions of psychosocial
      work situation, sleep disturbance and coping patterns at work on the one hand and
      performance during a test of physical strength and perceived effort during a
      muscular endurance test on the other. The physical strength of the shoulders
      flexors was measured. The subjective degree of effort was rated 60 and 90 seconds
      after the beginning of a test of isometric endurance of the neck extensor
      muscles. Four samples with numbers of about 80 subjects each were studied, first
      of all one sample of men and one of women from the general working population and
      secondly a sample of "super male" workers (furniture removers) and a sample of
      "service oriented female" workers (medical secretaries). The findings indicated
      that there is a relationship among men between self-reported coping strategies at
      work and results in the physical tests. Thus, in the random sample of men,
      individuals who described open coping patterns were found to perceive more effort
      after one minute and also after one minute and a half of the physical endurance
      test and were also found to be physically stronger than other individuals. Those
      who described themselves as less supported socially than other men reported more
      subjective effort and tended to be physically stronger than other individuals.
      Among furniture removers, those who described that they had a high degree of
      covert coping tended to report a higher degree of subjective effort after one
      minute. Among men in both groups, a high degree of sleep disturbance tended to be
      associated with more perceived effort during the endurance test.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7569824
TI  - Energy cost during ambulation in transfemoral amputees: a knee joint with a
      mechanical swing phase control vs a knee joint with a pneumatic swing phase
      control.
AB  - The aim of the study was (i) to evaluate the preference of transfemoral amputees
      for a 4-bar linked knee joint with either a mechanical swing phase control or a
      pneumatic swing phase control, and (ii) to compare the energy expenditure in
      transfemoral amputees using a prosthesis with a mechanical swing phase control
      with that of the same amputees using a prosthesis with a pneumatic swing phase
      control. The study included 28 unilateral transfemoral amputees amputated for
      reasons other than chronic vascular disease. All patients had a prosthesis with a
      knee joint with mechanical swing phase control (the Otto Bock 3R20) before
      entering the study. The amputees changed their knee joint to one with pneumatic
      swing phase control (the Tehlin knee joint) at random either after the first or
      second assessment. The amputees were asked for their preference at the second and
      third assessments. The energy expenditure while walking at speeds of 2 and 3 km/h
      was measured at each assessment. After having tried both knee joints, 19 patients
      preferred the Tehlin knee, 6 patients preferred the Otto Bock 3R20, and 3
      patients had no preference. The energy expenditure measurement showed that
      walking with the Tehlin knee required more energy than walking with Otto Bock
      3R20. Because of the limited number of patients included in the study and the
      fact that a double-blind design was impossible to achieve, conclusions should be
      drawn with caution.

PMID- 7569828
TI  - [Kidney transplantation and HLA matching: are Swiss guidelines in need of
      change?].

PMID- 7569825
TI  - Comparisons of mechanical and electromyographical muscular utilization ratios.
AB  - The physical loading of a muscle during functional activities can be estimated by
      the muscular utilization ratio. This ratio is defined as the percentage of
      muscular involvement relative to the maximal capacity. Either mechanical or
      electromyographical approaches can be used to obtain the muscle utilization
      ratio. However, the non-linear relationship between electromyographical activity
      and muscle force, as well as the non-equivalence between agonist muscles, may
      create differences between the mechanical muscle utilization ratio calculated
      from joint moments and the electromyographical muscle utilization ratio
      calculated from electromyographical data. The aim of this study was to compare,
      during a squat test, the mechanical muscle utilization ratio and the
      electromyographical muscle utilization ratio estimated by three different
      methods; direct linear approximation, second order polynomial regression and
      linear interpolation. The knee extensor moment and electromyographical data of
      rectus femoris and vastus medialis of 11 subjects were recorded during both knee
      extension and squat. Both tests were performed with the knee maintained at 90
      degrees of flexion. The results showed that: a) the electromyographical muscle
      utilization ratio, calculated from the average of vastus medialis and rectus
      femoris, significantly underestimates the mechanical muscle utilization ratio
      (ANOVA, p < 0.01), b) the differences between the mechanical muscle utilization
      ratio and the electromyographical muscle utilization ratio are larger for the
      direct linear approximation method than for the second order polynomial
      regression (ANOVA, p < 0.01) or the linear interpolation method (ANOVA, p <
      0.01), and c) independent of the method utilized, there is no difference between
      the electromyographical muscle utilization ratio predicted by the vastus medialis
      as compared with the rectus femoris (ANOVA, p > 0.01).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7569826
TI  - A clinical method for measuring segmental flexion mobility in the cervico
      thoracic spine and a model for classification.
AB  - Pain and limitation of spinal mobility are symptoms frequently reported by
      patients. Many methods have been used to assess the total range of mobility in
      the different parts of the spine, but there is no method for clinical examination
      of segmental mobility. The aim of this study was to describe such a technique
      concerning of segmental flexion mobility in the cervico-thoracic spine, C7-T5,
      and to present a model for classification of mobility. The results of this study
      show that the relative flexion mobility examined, according to the Cervico
      Thoracic-Ratio technique (CTR), may become a valuable complement to conventional
      methods of assessing mobility in the cervical spine. The normalized CTR values
      are less influenced by the individual factors age, body weight, height and number
      of years at work and the classification model presented makes functional analysis
      of segmental flexion mobility in the cervico-junction and upper thoracic spine
      more substantial.

PMID- 7569827
TI  - Acoustic cues and postural control.
AB  - The effect of auditory input on postural control was evaluated in separate
      experiments performed in three groups of healthy volunteers. Auditory input took
      the form either of feedback signals generated by a force platform in response to
      the subject's postural control movements, or of field orientation (frame of
      reference) input provided by repeated clicks emitted by loudspeakers in a
      normally reverberative environment. The effect of these acoustic cues was
      measured in terms of body sway recorded on a force platform during stance
      perturbations induced by vibratory stimuli applied to the calf muscles either at
      low (120mW) or high (850 mW) intensity, the subject standing with eyes closed or
      open, as instructed. In the presence of feedback auditory input, body sway in
      response to low intensity vibratory stimulation was significantly reduced, but
      not that in response to high intensity stimulation. This may be due to the fact
      that the head and body movements induced by high intensity vibratory stimulation
      are so rapid and powerful that they override the information available or to the
      subject using other strategies for postural control in which auditory feedback,
      at least in the form used here, does not contribute useful information. The
      availability of field orientation input did not reduce body sway in response to
      vibratory stimulation at low intensity. This was probably due to the cognitive
      lag which precluded use being made of the input before the fast proprioceptive
      responses to vibratory stimulation had already occurred.

PMID- 7569829
TI  - [Immunological aspects of kidney transplantation in Switzerland 1981-1992. Swiss
      Transplant Work Group Kidney Transplantation].
AB  - Every year some 200-260 kidney transplants are performed in Switzerland,
      improving the quality of life of patients with end stage renal disease. The
      current organ shortage is delaying transplantation of the 400 patients on the
      waiting list, a situation which calls for optimal utilization of the available
      donor kidneys. It is well established that AB0-compatibility, negative cytotoxic
      crossmatch, and optimal immunosuppressive therapy including cyclosporin A are
      important for a favorable clinical outcome. To identify further factors
      influencing transplant outcome, we undertook a retrospective study of all 1656
      transplants to which the above criteria applied. We defined transplants matched
      for at least 1A, 1B, and 1DR HLA antigen as the better matched, and the remainder
      as the less well matched grafts. In patients who were not or only weakly
      immunized to alloantigens, the 5-year graft survival probability was 0.78 versus
      0.69 for the better versus the less well matched transplants (p < 0.005). The
      strongly immunized patients did not, however, show a significant association
      between the degree of HLA matching and graft survival, presumably because there
      were more immunized patients in the HLA matched group. As expected, the patients
      previously immunized to alloantigens showed significantly reduced graft survival
      early after transplantation. Positive CMV serology, sex mismatch, and cold
      ischemia time did not correlate with graft survival. Compared to results obtained
      in the USA or Germany, the survival time of donor kidneys transplanted in
      Switzerland was significantly increased. Factors contributing to the good results
      in Switzerland are discussed. Future goals are reduction of alloimmunization and
      optimized HLA compatibility.

PMID- 7569830
TI  - [Prevention of postmenopausal osteoporosis: how effective is transdermal hormone
      substitution? (Continuous estradiol plus sequential oral norethisterone
      acetate)].
AB  - QUESTION: Can osteoporosis and cardiovascular risk be effectively and
      simultaneously prevented with transdermal estradiol replacement therapy (in
      combination with norethisterone acetate 1 mg per day, oral, cyclically for 12
      days monthly)? METHODS: A selected, representative group of healthy women with an
      average age of 52 years, with confirmed natural menopause for 1 to 4 years,
      randomly allocated to a treatment-group with hormone replacement (n = 42) and a
      control-group (n = 70), with homogeneous main parameters in the two groups, can
      be compared, without distortion of the findings, during the period of the two
      year intervention study: the purely trabecular bone mass in the distal radius was
      specifically measured, prospectively, with the highly accurate, three
      dimensional, peripheral quantitative computed tomography (thin-und multi-layer
      technology; Densiscan 1000) and the serum lipid, lipoprotein and apolipoprotein
      levels were measured (at the end of the gestagen cycle) in the morning fasting
      state. RESULTS: One-third of the persons of the control-group showed an annual
      loss of trabecular bone mass of more than 3.5%. These fast-losers, who on the
      basis of the annual bone-destruction rates are to be classified in the upper
      tertiles of the two groups, suffered a loss of trabecular bone of 4.2 +/- 0.4%
      (mean +/- SEM) in the treatment-group, compared with 7.3 +/- 1.0% in the control
      group in the first year; in the second year no loss of trabecular bone was
      observed in the treatment-group, while in the control-group the high rate of
      trabecular-bone destruction continued unchanged. The slow-losers (belonging to
      the middle and lower tertiles according to the bone loss rates) showed equally
      little change in their trabecular bone mass after the menopause, which can be
      described as physiological, with mean yearly values between -1.1 and +0.4%, both
      in the treatment-group and in the control-group. Under the transdermal hormone
      replacement therapy only the triglyceride and total cholesterol levels fell in
      comparison with the control-group, but without any significant changes in the
      atherogenic index, either in regard to the LDL/HDL or apolipoproteins B/A-I
      ratios. CONCLUSIONS: To be able to make valid statements it is necessary to study
      the effectiveness of a measure or of a preparation for the prevention of
      osteoporosis in fast-losers, who are to be randomized to the respective study
      groups and whose status has been confirmed by tests. Transdermal hormone
      replacement therapy--low estradiol dose in combination with NETA--stops the
      pathologically increased loss of trabecular bone only in the second year of the
      treatment; the antiatherogenic effect, however, is not confirmed. Only an
      individually adjusted therapy based on test results, with follow-up controls, can
      constitute an efficient, ethically justifiable postmenopausal prophylaxis of both
      osteoporosis and coronary heart disease.

PMID- 7569831
TI  - [Reconstructive surgery of the mitral valve in the acute stage of bacterial
      endocarditis. Apropos of 2 cases].
AB  - Two patients in our institution underwent mitral valve reconstruction during the
      acute phase of Staphylococcus aureus mitral valve endocarditis. In neither case
      was a pre-existing valve lesion found. Echocardiographic examination revealed
      severe mitral insufficiency and the extent of valvular lesions. In the first
      patient, prolapse of the posterior commissure and paracommissural areas was due
      to ruptured chordae tendinae. In the second patient a perforated abscess was
      surrounded by vegetations in the median portion of the anterior leaflet and
      paramedian anterior chordae tendinae were ruptured. The surgical indication was
      hemodynamic, combined with suspicion of repeated emboli in one case. After a 10
      day course of antibiotic therapy, both patients underwent surgical repair by
      Carpentier's mitral valvuloplasty. During more than 6 months' follow-up no
      recurrence of endocarditis was observed. Both patients were in class I of the
      NYHA without echocardiographic evidence of residual mitral regurgitation or
      stenosis. Early intervention during the acute phase of endocarditis, when mitral
      valve destruction is not too extensive, allows mitral valvuloplasty which
      preserves the native valve, eradicates infected tissues and may reduce
      postoperative mortality and morbidity.

PMID- 7569832
TI  - [How safe is laparoscopic colon surgery?].
AB  - Like any new technique, laparoscopic colon surgery must display results of the
      same or even better quality than established methods. In this hospital every
      laparoscopic colon operation has been registered since 1993. Patients were
      informed orally or in writing that the laparoscopic procedure is a new surgical
      technique and that, in particular, long term results in colon carcinoma are
      lacking. Patients who did not undergo the laparoscopic method were those who did
      not agree to this type of surgery, had tumor infiltrations without extensive
      liver metastases, or tumor sizes where laparotomy to retrieve the specimen is not
      much smaller than the open surgery incision. All operations without exception
      were performed by two laparoscopically skilled abdominal surgeons. We used four
      12 mm Troicarts placed in a diamond position, the criteria for mobilization and
      resection strictly following those of open surgery. In rectosigmoid resection the
      specimens were extracted suprapubically, with simultaneous implantation of the
      anvil, in the other cases at appropriate sites. The anastomoses were created
      either by the double stapling technique or with a single layer running suture. 88
      patients underwent operation. The change to open surgery was 11%. The reasons for
      the change were chiefly inflamed, bleeding diverticulitis tumor, carcinoma
      infiltrations and, in one case, bleeding. The anastomosis failure rate of the
      descendorectostomy, and in all laparoscopic colon operations, was 4% and compares
      favourably with the literature. This was also true of stenosis incidence. The
      wound infection rate is on the whole the same as for open surgery. The
      complication in the descendorectostomy is reduced by half in the laparoscopic
      procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569834
TI  - [60th Annual meeting of the Swiss Society of Gastroenterology and Hepatology.
      12th Annual meeting of the Swiss Group for Nutrition. Autumn meeting of the Swiss
      Society for Nutritional Research. Saint-Gall, 31 August-2 September 1995.
      Abstracts].

PMID- 7569833
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Transient lung
      infiltration with eosinophils. 1936].

PMID- 7569837
TI  - Gelastic epilepsy: Sturge-Weber syndrome with seizure facilitation.
AB  - A case with Sturge-Weber syndrome and ictal laughter is described. The seizures
      were facilitated by relaxation and drowsiness. The possible anatomic substrate
      and interconnections are discussed in the context of the localization of the
      lesion in this case.

PMID- 7569836
TI  - Vigabatrin in unsatisfactory controlled epilepsies. Swiss Vigabatrin Study Group.
AB  - One hundred and twenty-seven patients with uncontrolled epilepsy have been
      treated in an open add-on study with vigabatrin with a mean follow up of ten
      months. Mean duration of epilepsy prior to treatment was seven-teen years.
      Patients with partial seizures, with and without secondary generalisation
      responded best with 44% achieving a greater than 50% reduction in seizure
      frequency. Adverse events were primarily CNS related and reversible, two patients
      were withdrawn because of somnolence and eight because of behavioral
      disturbances. Reduction of concomittant AEDs was difficult in this population
      with chronic epilepsy.

PMID- 7569835
TI  - Unchanged incidence and prevalence of amyotrophic lateral sclerosis in the canton
      of Zurich.
AB  - The incidence and prevalence of amyotrophic lateral sclerosis (ALS) was
      determined for the canton of Zurich over the ten year period 1981-1990. The
      annual incidence rate was found to be 0.92 per 100,000 population, while the
      prevalence rate was 3.88 per 100,000 population, with a preponderance for males.
      Strong yearly fluctuations in the number of newly detected cases average out over
      the whole period with no trends of increased incidence. Data are within the range
      as reported from other industrialized countries.

PMID- 7569838
TI  - [Presence of Campylobacter spp., Clostridium difficile, C. perfringens and
      salmonellae in litters of puppies and in adult dogs in a shelter].
AB  - In order to ascertain the importance of Campylobacter spp., C.difficile,
      C.perfringens and Salmonella as agents of bacterial gastroenteritis in dogs, two
      groups of animals were studied prospectively. The first group consisted of 77
      puppies in 14 litters, with fecal cultures performed weekly for 10 weeks,
      starting at birth. The second group consisted of a kennel population with every
      dog cultured at entry, and at two-month intervals thereafter. Incidence of
      Campylobacter spp. was 32 and 31 per 100 dog-month of observation for healthy
      pups and healthy adult dogs respectively, 46 and 0 for C.difficile, 51 and 36 for
      C.perfringens and 6.5 and 1.3 for Salmonella. The incidence of Campylobacter spp.
      in pups peaked at 8 weeks of age. This incidence (43 per 100 dog-months) was
      higher in pups reared together with older dogs than in pups reared without
      contact to other dogs (0 per 100 dog-months). Toxigenic strains of C.difficile
      were found in 61.5% of the healthy neonate dogs. None of the cases of non-watery
      and non-inflammatory diarrhea we observed was associated with any of the
      pathogens studied. Furthermore newly acquired colonization with Campylobacter
      spp. or Salmonella was never associated with episodes of diarrhea. No conclusions
      could be drawn about the role of bacterial pathogens for causation of watery or
      inflammatory diarrhea which were not observed in our study.

PMID- 7569839
TI  - [Endoparasite infection in stray and abandoned dogs in southern Switzerland].
AB  - At their entry into the animal domicile, "La Stampa", in Lugano (canton Tessin),
      217 stray dogs and 154 unwanted dogs were examined for infections with intestinal
      parasites, filariae, Babesia and Leishmania. The following techniques were used
      for detection of intestinal parasites: combined sedimentation-flotation, MIFC
      technique and scotch tape adherence test. Prevalences of helminth egg excretion
      in stray dogs and in unwanted dogs, respectively, were as follows: 34% and 22%
      for Trichuris, 17% and 14% for Toxocara, 3% and 5% for hookworms, 4% and 0% for
      taeniids. Dipylidium, Toxascaris and Capillaria were diagnosed sporadically.
      Samples positive for taeniids were further tested for the presence of
      Echinococcus coproantigens in a sandwich ELISA: one of 9 dogs was strongly
      positive. This dog was euthanized for security reasons and upon dissection, 11
      Taenia hydatigena and more than 10,000 gravid Echinococcus granulosus worms were
      found. Microfilariae were detected in the blood of 3 stray dogs and one unwanted
      dog by the Difil-test. In all 4 cases the infective species was Dirofilaria
      immitis as confirmed by morphology, acid phosphatase activity analysis of
      microfilariae and by detection of specific antigens in blood plasma by ELISA.
      Specific antibodies against antigen of Leishmania infantum could not be detected
      in any of these dogs by ELISA. However, 3 stray dogs had specific antibodies
      against antigen of Babesia canis as demonstrated by IFAT.

PMID- 7569840
TI  - [Relapsing rhabdomyolysis in a greyhound. Description of a case].
AB  - A 3-year-old female Greyhound presents difficulties of locomotion in the hind
      limbs after one round of the field since the beginning of the racing season.
      After making a diagnosis of relapsing rhabdomyolysis without secondary renal
      involvement, several blood samples were taken before and after the effort in
      order to determine the most adequate moment for clinical evaluation of a rise in
      serum enzymes. The possibility of making an early diagnosis and a attempt for
      prevention are discussed. Blood values in a population of racing Greyhounds are
      compared with data of the literature.

PMID- 7569843
TI  - [Veterinarians and tumor patients--reflections on ethics].

PMID- 7569841
TI  - [What is your diagnosis? Congenital pulmonary stenosis with signs of a distinct
      diminishing lung perfusion].

PMID- 7569844
TI  - [Preliminary results using a combined xylose absorption/hydrogen exhalation test
      in horses].
AB  - In the present study the breath hydrogen (H2) excretion test was combined with
      the xylose absorption test in 4 normal horses and 9 clinical patients with
      chronic diarrhea (n = 3) or chronic weight loss without diarrhea (n = 6). All
      horses underwent a thorough clinical examination. Laboratory evaluations
      consisted of haematology and serum biochemistry as well as bacteriological and
      parasitological examination of feces. In addition, serum electrophoresis and
      abdominocentesis was performed in all the clinical patients. Gastroscopy was
      carried out in 6 patients and rectal biopsies were obtained from 4 animals. Two
      animals were euthanized within 4 weeks after the evaluation. The diagnosis of
      chronic granulomatous enteritis was confirmed in one of them at necropsy, the
      cause of weight loss in the other remained unexplained. In the remaining animals,
      specific causes such as management, parasites, chronic infections and diseases of
      liver, kidneys and heart were excluded, but no specific diagnosis could be
      obtained. For the combined xylose absorption/H2 excretion test, the animals were
      starved overnight and given 0.5/kg/bwt xylose as a 10% solution by stomach tube
      the next morning. Blood samples were collected for plasma xylose analysis at 30
      min intervals for 4 hrs, and breath samples were also collected at 30 min
      intervals for 8 hrs. With the exception of the animal with granulomatous
      enteritis, the diseased horses showed only slight alterations in either peak
      concentrations or times to reach peak levels of plasma xylose. None of the
      healthy animals showed an increase in breath H2 production after xylose
      administration, whereas five of the diseased animals showed distinct increases of
      variable heights. In addition, the diseased horses showed higher fasting breath
      H2 levels (range 7.5-61.5 ppm) than normal horses (range 0-5 ppm). It is
      concluded that gastrointestinal disorders might be influenced or even induced by
      a change in intestinal microbial composition, as evidenced by an increased
      hydrogenic metabolism.

PMID- 7569842
TI  - Echocardiographic diagnosis of a cardiac fibrosarcoma in the right atrium of a
      sheep.
AB  - This is a case report of a six-year-old female White Alpine sheep with a cardiac
      fibrosarcoma in the right atrium. Clinically, the sheep had right-sided cardiac
      insufficiency with tachycardia, engorgement of the jugular veins, brisket edema,
      and ascites. Chronic congestion of the liver resulted in increased hepatic enzyme
      activity. Based on clinical findings, a tentative diagnosis of endocarditis or
      pericarditis was made. Radiography of the thorax revealed hydrothorax. An
      echogenic mass was observed in the right atrium via echocardiography; it was
      interpreted as a tumor or thrombus. Ultrasonography of the abdomen revealed
      severe ascites and chronic congestion of the liver attributable to right-sided
      cardiac insufficiency. The clinical and sonographic findings were verified at
      post mortem. The mass in the right atrium was a pedunculated fibrosarcoma.

PMID- 7569845
TI  - [Case report: polycythemia in a horse].
AB  - A 13 year old Thoroughbred gelding was presented with a history of a single
      episode of collapse during mild exercise. Clinical examination revealed a high
      packed cell volume (PCV) of 72%, a haemoglobin concentration of 24.9 g/l and 15.2
      millions erythrocytes/microliters. Despite continuous intravenous infusion
      therapy with large volumes, the PCV never decreased to a physiological level. The
      animal showed a normal appetite and no signs of discomfort or syncope. Arterial
      blood gas values were in the normal range as well as the concentration of
      erythropoietin (measured by radioimmunoassay, RIA). A test for neoplasms (carcino
      embryonic antigen, CEA) was negative. The liver enzymes of the animal were
      extremely elevated and a liver biopsy showed a severe fibrosis. Examination of
      sternal bone marrow aspirate revealed no abnormalities. Based on these findings,
      the presumptive diagnosis was "absolute polycythaemia". The animal was treated
      for 7 days with repeated phlebotomy. During this time, the PCV never decreased
      below 50%, despite no obvious signs of discomfort from the animal. Because of the
      poor prognosis based on the liver biopsy result, the animal was euthanized 11
      days after hospitalization. Post mortem findings were: a granular cell
      myoblastoma with a diameter of approximately 5 cm in the lungs, severe fibrosis
      of the liver, mild acute tubular nephrosis in the kidneys, activation of the
      erythropoietic cells in the bone marrow and thrombosis of the abdominal aorta.
      The possibility of secondary polycythaemia due to the lung neoplasia was not
      entirely excluded, but considered to be unlikely. Therefore, the definite
      diagnosis was polycythemia vera.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7569846
TI  - [Sedation and anesthesia in dogs and cats with cardiovascular diseases. I.
      Anesthesia plan considering risk assessment, hemodynamic effects of drugs and
      monitoring].
AB  - The purpose of this study was to review the effects of sedatives and anesthetics
      in 137 dogs and 13 cats with congenital or acquired heart disease which were
      referred for diagnostic, therapeutic, and surgical interventions: correction of
      patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with
      angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory
      lateral thoracotomy (8.7%), correction of right aortic arch (ring anomaly, 3.3%),
      correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in
      patients with mitral regurgitation and congestive heart failure (2%),
      pericardectomy and removal of heart-base tumors (2%), palliative surgery for
      ventricular septal defect (VSD, 0.7%), and sick patients with deleterious cardiac
      arrhythmias (0.7%). The anesthetic plan considered the risks of anesthesia based
      upon preoperative patient assessment, classification scheme for functional phases
      of heart failure, and anesthetic drug effects of the cardiovascular system. The
      effects of sedatives and anesthetic drugs on determinants of cardiac output are
      described. The most commonly used drugs for premedication, induction, and
      maintenance of anesthesia were midazolam-oxymorphone (20%), thiopental or
      etomidate (30%), and isoflurane (64%). Prompt therapy was given to control
      arrhythmias and provide organ perfusion, pain relief, muscle relaxation and renal
      diuresis, using lidocaine, dopamine, fentanyl, atracurium, and furosemide in
      17.3% 14.7%, 12%, 10%, and 8.7% of animals, respectively. Methods of routine and
      advanced patient monitoring are described.

PMID- 7569847
TI  - Survivors: relationship between persons with cancer and spinal cord injury.

PMID- 7569848
TI  - President's message: changes ... implications of spinal cord injury.

PMID- 7569849
TI  - Pressure ulcers and wound healing: educating the spinal cord injured individual
      on the effects of cigarette smoking.
AB  - While it is well known that smoking causes an increased risk of lung cancer and
      cardiovascular problems, there is little information available about cigarette
      smoking and its adverse effects on pressure ulcers and wound healing in the
      individual with spinal cord injury (SCI). Due to SCI, circulation is already
      compromised. Smoking has a vasoconstrictive effect on the capillaries at the
      dermal level, which diminishes the amount of oxygenated blood reaching the
      tissues, further delaying the healing process of pressure ulcers and surgical
      wounds (Ting, 1991). A study was developed to focus on the knowledge of smoking
      among individuals with SCI. A video tape was prepared to provide comprehensive
      information about smoking. Twenty male patients with SCI were selected at random
      to view the videotape. A pre-test and post-test were given to evaluate the
      individual's knowledge of the effects of smoking on wound healing. The data
      collected demonstrated the effectiveness of the videotape as a teaching tool for
      increasing awareness of the adverse effects of cigarette smoking on pressure
      ulcer prevention and wound healing. Educating the individual with SCI on the
      effects of cigarette smoking is an important aspect of health education that
      needs to be addressed.

PMID- 7569851
TI  - The skeleton after spinal cord injury. Part 1. Theoretical aspects.
AB  - Sublesional osteoporosis occurs after acute spinal cord injury (SCI),
      preferentially weakening the skeleton below the level of the neurological lesion.
      Although its pathogenesis is unclear, it resembles post-menopausal, high turnover
      osteoporosis. Physical and pharmacologic therapies are currently being tested for
      their ability to prevent early loss and restore lost bone. Although treatment
      strategies hold promise, preservation of skeletal strength after injury may
      ultimately rest on lifestyle decisions made early in life. If skeletal strength
      is to be maintained after SCI, ways must be found to optimize skeletal strength
      prior to injury, arrest early losses, and stabilize, if not restore, lost bone
      over time.

PMID- 7569852
TI  - Coordinated care for the SCI patient.
AB  - The delivery of quality patient care in a timely, cost-effective manner is of
      utmost importance in health care settings. In an attempt to promote continuity
      and coordination of care, appropriate utilization of resources, and increased
      patient and health care provider satisfaction, a coordinated care system of
      patient care delivery was implemented for the spinal cord injured patient.
      Coordinated care is a multi-disciplinary approach that focuses on achieving
      patient outcomes within effective time frames which have been established by all
      members of the health care team involved in the treatment of the SCI patient.
      Integral to the concept of coordinated care is the utilization of a critical path
      and variance tracking and analysis. A critical path is a multidisciplinary plan
      which identifies the time frame in which key events and patient outcomes should
      occur during an episode of care in order to achieve an optimal use of resources
      and length of stay. Variance tracking is the comparison of the actual care
      delivered with the expected plan and the identification of reasons why the care
      differed.

PMID- 7569854
TI  - How to use research based literature in practice.

PMID- 7569853
TI  - Evaluation of bone resorption: a common problem during impaired mobility.
AB  - Osteoporosis, the result of an imbalance between bone resorption and bone
      formation, is a potential problem for the individual with a spinal cord injury
      because of the immobility commonly associated with this impairment. This study
      was performed to determine the diagnostic value of a new assay for urinary
      Pyridinium crosslink (UPyr). Assays were performed on 62 first morning voided and
      50 24-hour urine specimens from clients in a bone health clinic. Higher than
      normal levels of UPyr were observed in females with osteoporosis. UPyr correlated
      well with urinary hydroxyproline (r = 0.429, p = 0.005; conversely, there was an
      inverse relationship between bone density and UPyr (r = -0.489, p = 0.01),
      positive correlation (r = 0.43, p = 0.011) between the 24-hour UPyr and a serum
      marker of bone resorption. The study confirms that UPyr has the ability to
      identify states of high bone resorption. This assay should be a welcome addition
      to the bone health assessment of individuals with risk factors such as impaired
      physical mobility.

PMID- 7569850
TI  - Using personal assistance services after spinal cord injury: the role of the
      nurse.
AB  - Many people with spinal cord injury (SCI) need a personal assistant (PA) to help
      them with activities of daily living. Personal assistance services can make a
      critical difference in adjustment to SCI and the ability to live independently.
      Using the independent living model, the person with a disability (employer)
      directs and monitors his/her health care needs. This article focuses on two
      essential skills needed by the employer of a personal assistant: 1) creation of a
      thorough job description using checklists and 2) communication skills needed to
      supervise the PA. Knowledge of these management skills will enhance the nurse's
      practice when working with clients who are new or experienced in using personal
      assistance services.

PMID- 7569855
TI  - [Use of 3D ultrasound technique in prenatal diagnosis].
AB  - Within a few years 3-dimensional prenatal ultrasound has achieved such a high
      standard that this technique opens up a new way of image rendering in prenatal
      diagnosis both for the examiner and for the patient. Using a 3-D ultrasound
      probe, data acquisition and storage of defined volumes is possible under routine
      conditions. Within the stored volume every dimension can be visualised and high
      quality 3-D surface and translucency images can also be provided rapidly. In
      prenatal diagnosis the advantages are not only in demonstrating precisely the
      extent of a defect, especially of the surface, but also to convince the parents
      concerned by clear demonstration of the absence of a specific defect. In 3-D
      technology there are still some problems to be solved: in severe oligohydramnios,
      no surface images can be provided, and in the examination of moving objects
      movement artifacts can occur. On the other hand, improvements in computer
      technology will soon provide an accelerated image rendering.

PMID- 7569856
TI  - [Ultrasound studies in afterloading therapy of uterine malignancy].
AB  - The afterloading technique for radiation therapy of gynaecologic malignancies has
      significant advantages for the patients as well as the medical staff: a reduced
      risk of perforating the uterus, more accurate treatment planning, a more
      agreeable treatment environment for the patients and, most importantly, a
      significant reduction of radiation exposure for the medical staff. Using simple
      ultrasound methods, the localisation and the extent of the tumour to be treated
      by radiation therapy can be assessed. With these data, the suitable isodose
      curves are selected. The distance to adjacent organs, especially of the loops of
      bowel next to the uterus which are normally not reached by dosimetric probes, can
      be estimated and the information included into treatment planning, thus reducing
      the risk of radiation side effects. Furthermore, the insertion of afterloading
      applicators and dosimetric probes can be checked by ultrasound making injury to
      the uterus and other organs less likely. At the same time, the correct position
      of the instruments is verified. For the ultrasonographic evaluation of the
      radiation response of primarily irradiated carcinomas more data are needed.

PMID- 7569857
TI  - [Visualization of the inferior mesenteric artery in the ultrasound B image].
AB  - AIM: Reports in the literautre differ widely with regard to visualisation of the
      inferior mesenteric artery (IMA) by B-mode ultrasonography. Hence, our study
      aimed at obtaining exact data on the feasibility of visualising the inferior
      mesenteric artery via B-mode ultrasonography in a relatively large patient
      population. METHOD: At the outpatient department of gastroenterology and
      hepatology 51 males (aged 14 to 75 years) and 53 females (aged 16 to 79 years)
      were examined consecutively by two experienced investigators via B-mode scan
      within the overall framework of a routine screening programme, in each case after
      overnight fasting. Knowledge of normal anatomic conditions and of the possible
      variations of the IMA is mandatory for correct IMA visualisation. RESULTS: We
      succeeded in visualising the IMA via B-mode scan in 41 of the 51 males (80.39%)
      and in 40 of the 53 females (75.47%), i.e. in a total of 81 of 104 patients
      (77.88%) in 2-3 cm length. CONCLUSION: The results show that IMA can be
      visualised by B-mode ultrasonography in a manner comparable to visualisation of
      the superior mesenteric artery (82). This is an essential finding, since duplex
      sonography of the IMA yields important information on disease activity in
      inflammatory bowel disease, and B-mode scanning of the IMA is the prerequisite
      for duplex scanning.

PMID- 7569858
TI  - [Intrarenal color Doppler ultrasound for exclusion of renal artery stenosis in
      cases of multiple renal arteries. Analysis of the Doppler spectrum and tardus
      parvus phenomenon].
AB  - PURPOSE: To diagnose possible renal artery stenosis especially in case of
      multiple renal arteries by intrarenal colour-coded Duplex sonography. METHODS: In
      50 hypertensive patients lobar and interlobar arteries were looked for at 3
      different levels. Analysis included the determination of the early systolic
      acceleration time and the assessment of the Doppler waveform, especially the
      "tardus-parvus" phenomenon. Intraarterial angiography was performed in all
      patients the next day. RESULTS: In 48/50 patients the sonographic investigations
      were sufficiently evaluable. Angiography showed haemodynamically relevant
      stenosis in 13 patients, in 4 patients bilaterally. In 21 patients (42%) multiple
      renal arteries were found. Sensitivity and specificity in the diagnosis of renal
      artery stenosis was 77% respectively 46% (threshold value > or = 0.120 s). In
      10/17 angiographically verified haemodynamically relevant renal artery stenosis a
      change of the Doppler waveform was noted; sensitivity in the diagnosis of renal
      artery stenosis was 69%, specificity 90%. CONCLUSION: Intrarenal colour-coded
      Duplex sonography cannot be recommended as a screening tool for renal artery
      stenosis.

PMID- 7569859
TI  - [Ultrasound morphologic parameters of female stress incontinence].
AB  - AIM: The study compared ultrasound parameters of the lower urinary tract with
      patients' age, number of previous pregnancies as well as the grade of
      incontinence. Furthermore, the influence of postural changes was studied. METHOD:
      Ultrasonographic examination of the vaginal introitus was performed on 222
      patients using a 5 MHz scanner. The transducer was inserted along the body axis
      and a vertical plane was defined. RESULTS: Urinary stress incontinence was found
      to be associated with the occurrence of cystoceles, the finding of a funnel-like
      opening of the proximal urethra, an increased retrovesical angle beta, and
      finally with a descent of the bladder neck. However, there was no significant
      correlation between urethral length and the grade of stress incontinence. In
      patients without urinary incontinence, the retrovesical angle as well as the
      position of the bladder neck were strongly related to parity but did not
      correlate with the patients' age. There was no significant difference between
      parameters when the patients were straining in a prone or half-prone position.
      CONCLUSION: Sonomorphological pelvic floor disorder is based on previous
      pregnancies and correlates well with urinary stress incontinence.

PMID- 7569861
TI  - [The exencephaly-anencephaly sequence. Ultrasound diagnosis in early pregnancy].
AB  - AIM: In animal studies exencephaly is well described as a precursor of
      anencephaly. We have evidence that also in the human fetus the transition from
      exencephaly to anencephaly is possible. METHOD: We diagnosed either exencephaly
      or anencephaly by high-frequency vaginal ultrasound in 14 human fetuses at
      gestational ages varying between 9 + 4 and 22 + 3 weeks. RESULTS: In the first
      trimester exencephaly was the predominant finding, while in the second trimester
      the classic appearance of anencephaly was seen more often. In one fetus with
      exencephaly diagnosed at a gestational age of 12 + 2 weeks, where the parents
      decided not to intervene, the transition to anencephaly was documented by serial
      ultrasound examinations. CONCLUSIONS: Our findings support an exencephaly
      anencephaly sequence also in humans. The cephalic changes resulting in the
      classic anencephalic appearance are of importance for the first trimester
      diagnosis with high resolution vaginal probe ultrasound.

PMID- 7569860
TI  - [Ultrasound anatomy of the fetal hip joint with special reference to the blood
      supply].
AB  - AIM: Study of the anatomy of the fetal hip joint in 115 pregnancies between 13.
      to 40.th weeks of gestation by ultrasound. METHOD: Sonoanatomy was studied by
      high resolution ultrasound (Acuson 128). For investigation of vascular supply of
      the fetal hip, colour-coded Doppler sonography was performed. In-vivo studies on
      vascular supply were correlated with histological sections of 34 fetal hip
      specimens, according to the conceptional age of 13-35 weeks. RESULTS: Vascular
      studies of the proximal end of the human femur showed a supply by the lateral and
      medial femoral circumflex arteries branched from the femoral artery or the deep
      femoral artery. After 22 weeks of gestation the acetabular artery supplied by the
      obturator artery was visible by means of Doppler sonography. At the end of
      pregnancy, large numbers of intraosseous blood vessels are demonstrable within
      the femoral head and neck. CONCLUSION: The basic arterial pattern of the hip
      joint is established at birth. Proximal end of the growing femur, acetabulum, os
      ilium and labrum acetabulare are clearly visible by ultrasound.

PMID- 7569862
TI  - [Ultrasound of extremity lesions caused by birth trauma].
AB  - With regard to injuries of the extremities caused by birth trauma, ultrasound
      allows simultaneous direct evaluation of the surface of osseous elements and of
      cartilaginous and soft-tissue structures as well. Thus, not only fractures, but
      also concomitant articular fluid collections, respectively haematomas and/or
      dislocation of an epiphysis are demonstrated in their initial extent and in their
      course of healing. Additionally, closed repositions, for instance of a displaced
      epiphysis, can be exactly monitored by ultrasound. A reduced number of
      roentgenograms as well as renunciation of other imaging modalities are the
      consequence. Own experiences in 4 patients with birth trauma to the humerus
      confirm the high validity of ultrasound in this area as well.

PMID- 7569864
TI  - Prevention of colorectal cancer by screening flexible sigmoidoscopy: possible
      role of the primary care physician.

PMID- 7569863
TI  - [Coronary aneurysm in a 69-year-old patient. Transthoracic echocardiography].
AB  - This case report is on a 69-year old male patient treated with cephalosporins
      because of suspected myocarditis due to borreliosis. Using transthoracic
      echocardiography a big aneurysm of the proximal part of the left coronary artery
      was detected. Coronary angiography revealed an aneurysm 1.2 cm in diameter at the
      origin of the left anterior descending branch and confirmed the initial
      diagnosis. In addition, coronary three-vessel disease with reduced left
      ventricular function was found. Coronaritis due to Lyme borreliosis could not be
      ruled out with certainty. The patient was relatively asymptomatic, and hence
      conservative therapy was recommended. The case described here serves as a basis
      for a discussion on the aetiology, clinical manifestation, diagnosis and
      therapeutic management of coronary aneurysms.

PMID- 7569865
TI  - The role of endothelin-1 in cardiovascular physiology and pathophysiology.

PMID- 7569866
TI  - Phacoemulsification: small incision cataract surgery.

PMID- 7569867
TI  - AIDS related cholangitis.

PMID- 7569868
TI  - Evidence that oilseed rape (Brassica napus ssp. oleifera) causes respiratory
      illness in rural dwellers.
AB  - A study of 25 residents in a small Scottish village over a two-year period
      investigated respiratory symptom reporting in the presence or absence of oilseed
      rape. Symptom reporting in the year when oilseed rape virtually surrounded the
      village, varied during the growing season of the crop and was at its highest
      coincident with peak flowering. At the same period of the following year when the
      crop was absent, symptom reporting was significantly lower. The symptoms which
      correlated most strongly with peak oilseed rape flowering were sneezing, cough,
      headache, eye irritation and the total of these and other symptoms. Increased
      symptoms were reported by 12 of the participants though only seven of these were
      judged to be atopic. The symptoms did not correlate with levels of oilseed rape
      pollen but there is no clear evidence as to which of the other factors associated
      with the crop might be the cause.

PMID- 7569870
TI  - Women's experiences at cervical screening.
AB  - Concerns about attendance for cervical screening has focussed on determining the
      reasons why some women never attend. Less attention has been paid to whether
      women continue to attend for further smears, although this is essential for
      further screening. This study investigated women's experiences of cervical
      screening and their views on subsequent attendance. Three hundred and thirty nine
      women aged 20-64 were identified from a computerised register of cervical smears
      as having had a smear test within the previous three years. They were interviewed
      at home about their most recent experience of screening. Just over half of the
      women (53%) recalled being anxious before the test, and about one fifth reported
      embarrassment (19%) or pain (20%) during it. The frequencies of discomfort were
      higher amongst those who were anxious about the test, although 24% of those who
      were embarrassed and 28% who had pain reported being unconcerned beforehand. The
      frequencies of pain and embarrassment were only slightly higher when the smear
      taker was male. Many women (22%) reported being concerned about the test result
      although only 10% of those who were concerned were recalled for further
      assessment. Although a number of women had unpleasant experiences, almost all
      (95%) who were under 60 years of age said they were likely to attend for a
      subsequent smear. Taking cervical smears is often an unpleasant experience for
      women, although some of the distressing events could easily have been avoided.
      Attention to technique and to the concerns of individual patients, especially
      ensuring privacy, could reduce the extent of the problem. The uptake of
      subsequent smears should be monitored to ensure that women are not being
      discouraged from attendance.

PMID- 7569869
TI  - The health status and health needs of Chinese population in Glasgow.
AB  - This cross sectional study explored the health problems and health needs in the
      local Chinese community in Glasgow. Several data collection methods have been
      used in this study, including face-to-face and telephone structured interviews,
      postal and hand delivered questionnaires. A total of 800 questionnaires were
      processed, and 493 were completed, giving an overall response rate 61.6%. The
      results from the present survey indicated that the health status of Chinese
      residents in Glasgow is poorer than that of the local population. The most
      important findings of the study is that the Chinese community in Glasgow underuse
      health services, and unmet health needs exist in the community. The main barrier
      to effective use of present health services and benefit from the health promotion
      and health education programmes is language difficulties. Following discussion
      with the local community, options for improving the health services for the
      Chinese community in Glasgow were obtained. The findings of the study have
      implications for health service purchaser/providers of health care to the Chinese
      population generally in Scotland.

PMID- 7569871
TI  - The value of a travel history in urology.
AB  - We report a case of a young British woman who contracted urinary schistosomiasis
      while on holiday in Africa, having swum in Lake Malawi. A travel history would
      have been helpful in reaching the diagnosis earlier. The diagnosis was made after
      biopsy of an unusual bladder mucosal lesion and effective treatment given but it
      could easily have been missed, with the disease's resulting sequelae.

PMID- 7569872
TI  - Medical affairs in the Far East after V-J day. A personal view.
AB  - The invasion of Singapore and Malaya was delayed because of the reduction in the
      period of service in the Far East. The atom bombs were then dropped and plans for
      all services including medical ones had to be altered, their main aim becoming
      the treatment and repatriation of surviving prisoners of war. The ending of the
      war did not occur abruptly on V-J day; many Japanese troops had to be convinced
      that the war was over. Meantime the treatment of diseases in British and other
      service men continued; reference is made to some experiences in Rangoon. The
      morale of personnel who now were anxious to return to their homes was low and
      efforts were made to raise their spirits. In India it was accepted that the days
      of British rule were over.

PMID- 7569874
TI  - Combination therapy for NIDDM: has its time arrived?

PMID- 7569873
TI  - Illness and the psyche.

PMID- 7569875
TI  - Collection of domestic waste. Review of occupational health problems and their
      possible causes.
AB  - During the last decade, a growing interest in recycling of domestic waste has
      emerged, and action plans to increase the recycling of domestic waste have been
      agreed by many governments. A common feature of these plans is the implementation
      of new systems and equipment for the collection of domestic waste which has been
      separated at source. However, only limited information exists on possible
      occupational health problems related to such new systems. Occupational accidents
      are very frequent among waste collectors. Based on current knowledge, it appears
      that the risk factors should be considered as an integrated entity, i.e.
      technical factors (poor accessibility to the waste, design of equipment) may act
      in concert with high working rate, visual fatigue due to poor illumination and
      perhaps muscle fatigue due to high work load. Musculoskeletal problems are also
      common among waste collectors. A good deal of knowledge has accumulated on
      mechanical load on the spine and energetic load on the cardio-pulmonary system in
      relation to the handling of waste bags, bins, domestic containers and large
      containers. However, epidemiologic studies with exposure classification based on
      field measurement are needed, both to further identify high risk work conditions
      and to provide a detailed basis for the establishment of occupational exposure
      limits for mechanical and energetic load particularly in relation to pulling,
      pushing and tilting of containers. In 1975, an excess risk for chronic bronchitis
      was reported for waste collectors in Geneva (Rufener-Press et al., 1975) and data
      from the Danish Registry of Occupational Accidents and Diseases also indicate an
      excess risk for pulmonary problems among waste collectors compared with the total
      work force. Surprisingly few measurements of potentially hazardous airborne
      exposures have been performed, and the causality of work-related pulmonary
      problems among waste collectors is unknown. Recent studies have indicated that
      implementation of some new waste collection systems may result in an increased
      risk of occupational health problems. High incidence rates of gastrointestinal
      problems, irritation of the eye and skin, and perhaps symptoms of organic dust
      toxic syndrome (influenza-like symptoms, cough, muscle pains, fever, fatigue,
      headache) have been reported among workers collecting the biodegradable fraction
      of domestic waste. The few data available on exposure to bio-aerosols and
      volatile compounds have indicated that these waste collectors may be
      simultaneously exposed to multiple agents such as dust containing bacteria,
      endotoxin, mould spores, glucans, volatile organic compounds, and diesel exhaust.
      Several studies have reported similar health problems as well as high incidence
      rates of pulmonary disease among workers at plants recycling domestic
      waste.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7569876
TI  - Longevity and selenium deficiency: evidence from the People's Republic of China.
AB  - Data were abstracted from the Atlas of Aged Population in the People's Republic
      of China and from The Atlas of Endemic Diseases and their Environments in the
      People's Republic of China. The spatial distribution of the elderly, those aged
      80 years or more in 1982, in 2408 counties, was then compared with the
      prevalences of Kaschin-Beck and Keshan diseases, both of which involve extreme
      selenium deficiency. Pearson chi-square, the Mantel-Haenszel test for linear,
      association and Spearman correlation all clearly indicate that the elderly in
      China are not normally distributed. Far fewer people of advanced age reside in
      those counties in which Kaschin-Beck and Keshan diseases are endemic than in
      unaffected counties. The possible reasons for this are thought to include
      elevated mortality from endemic and chronic diseases in selenium deficient areas
      and accelerated ageing due to excessive cellular damage caused by free radicals.
      These two phenomena may be related.

PMID- 7569877
TI  - Atmospheric deposition of cosmogenic 7Be and 137Cs from fallout of the Chernobyl
      accident.
AB  - Atmospheric (tropospheric) depositional fluxes of the naturally occurring 7Be of
      cosmogenic origin and 137Cs from fallout of the Chernobyl accident were measured
      over a 7-year period (January 1987-December 1993) at Thessaloniki, Greece (40
      degrees 38' N, 22 degrees 58' E). The annual total deposition fluxes of 7Be
      varied between 854 Bq/m2 (1987) and 1242 Bq/m2 (1992), showing a minimum in the
      years 1988-89. The annual total deposition fluxes of 137Cs varied between 183
      Bq/m2 (1987) and 16.4 Bq/m2 (1992), showing a significant decrease as expected
      for natural removal and radioactive decay and no new releases from nuclear
      facilities or weapons testing. The annual average total deposition velocity for
      7Be was from 0.3 cm/s (1988) up to 0.8 cm/s (1991), while for 137Cs the
      corresponding values were much higher, hence 137Cs was associated with larger
      atmospheric particles. High 7Be concentrations in air were related to the very
      little solar activity (1987-88 and 1993-94), while low 7Be concentrations in air
      related to the high solar activity (1989-91). Maximum 137Cs concentrations in air
      were registered during the spring 1991 and 1992, reflecting some stratospheric
      inputs. An unusual highly elevated value of 137Cs concentration in air, reaching
      0.25 mBq/m3, was observed during the summer 1990.

PMID- 7569878
TI  - Testing and classification methods for the biodegradabilities of organic
      compounds under anaerobic conditions.
AB  - Biodegradability is one of the most important characteristics of an organic
      compound for predicting its fate and life in the environment and its application
      in biological wastewater treatment. But there is no general testing method for
      biodegradability under anaerobic conditions. The biodegradabilities of thirteen
      principal organic compounds was investigated in a batch test using vials under
      various conditions, such as the concentration of an organic compound, the
      cultivation method and the concentration of anaerobic bacteria for seeding. Two
      test methods in the standard concentration and the low concentration were
      developed. A new method to classify the biodegradabilities of organic compounds
      into thirteen ranks was proposed by considering inhibition, complete
      biodegradation and first step biodegradation.

PMID- 7569879
TI  - Biodegradation ranks of priority organic compounds under anaerobic conditions.
AB  - The biodegradations of 52 priority organic compounds were evaluated under
      anaerobic conditions by two tests developed in a preceding paper (Urano et al.,
      1995). Namely, the biodegradabilities of the compounds were classified into 13
      ranks by the method proposed by Urano et al. (1995). Most of the aliphatic
      alcohols and carboxylic acids were not inhibitory and were biodegraded, but the
      compounds having ether bonds or branched hydrocarbon groups were biodegraded
      slowly. Aliphatic aldehyde and amines were not so much inhibitory but were hardly
      biodegraded. The benzene substitutes having groups of -CH2OH, -CHO, 
      CH2CH(NH2)COOH, -COOH and -OH were easily biodegraded, but the compounds having
      groups of -NO2, -NH2 and -SO3H were hardly biodegraded. Most of the nitro
      compounds were inhibitory in the higher concentration test though they were
      reduced into amino compounds. Since the biodegradation characteristics of many
      organic compounds could be classified and discussed appropriately, the
      suitability of the proposed method is substantiated.

PMID- 7569880
TI  - Cadmium and zinc relationships in the liver and kidney of humans exposed to
      environmental cadmium.
AB  - Concentrations of cadmium and zinc were determined in the liver and in the kidney
      (cortex and medulla) of subjects from the general population of Barcelona (Spain)
      by atomic absorption spectrometry. Tissues were collected from necropsies of 50
      selected subjects without any occupational exposure to heavy metals. Cadmium
      levels calculated on a fresh tissue basis were 14.6 +/- 5.9 micrograms/g (2.4-31)
      in the kidney cortex, 8.6 +/- 4.3 micrograms/g (1.5-16.7) in the kidney medulla
      and 0.98 +/- 0.50 micrograms/g (0.32-2.32) in the liver. Zinc concentrations
      ranged between 18-53 micrograms/g, (mean +/- S.D.: 38.0 +/- 10 micrograms/g) in
      the kidney cortex, 25.0 +/- 7.7 micrograms/g (12-42 micrograms/g) in the kidney
      medulla and 41.7 +/- 18.3 micrograms/g (20-84 micrograms/g) in the liver. The aim
      of the present work was to study the association of cadmium and zinc in the
      kidney and in the liver of a human population with cadmium accumulation from an
      environmental origin. The results obtained showed a significant correlation
      between cadmium and zinc concentration in the liver (r = 0.86, P < 0.001), but
      not in the kidney.

PMID- 7569881
TI  - Long term behaviour and degradation kinetics of tributyltin in a marina sediment.
AB  - One-meter sediment cores sampled in a marina have been submitted to extensive
      characterization and organotin speciation. Geochemical homogeneity has been
      demonstrated. Butyltin species are present at all depths with a predominance of
      TBT or MBT in the upper or lower layers, respectively. Seasonal variations of
      butyltin compounds have been identified and together with a knowledge of local
      conditions we estimate the sediment layers represent 14 years of deposition. A
      first order multi-step kinetic model of the sequential degradation of TBT in,
      successively, DBT, MBT and Sn (IV) is proposed. The half-life of TBT was
      estimated (on a 14-year period) to be 2.1 years and those of DBT and MBT (on a 5
      year period) 1.9 and 1.1 years, respectively.

PMID- 7569882
TI  - Lead concentration and the level of glutathione, glutathione S-transferase,
      reductase and peroxidase in the blood of some occupational workers from Irbid
      City, Jordan.
AB  - Blood samples were collected from 263 lead-exposed suspected males living in
      Irbid area in the northern part of Jordan. The blood lead concentrations in the
      samples were determined by atomic absorption and were related to the type of work
      performed by the workers. The blood lead concentration was higher in metal
      casters, 41.6, and radiator welders, 32,8 micrograms/dl, compared to non
      suspected lead-exposed university students, 5.7 micrograms/dl. Workers such as
      mechanics, bus drivers, car painters and gas station workers showed slightly
      higher but not significant blood lead. The blood glutathione content and the
      activities of glutathione reductase, glutathione peroxidase and glutathione S
      transferase were also determined in non-suspected subjects and in those with
      occupational exposure to lead. With increasing blood lead concentration,
      glutathione content decreases as well as the activities of the glutathione
      utilizing enzymes.

PMID- 7569884
TI  - Radioactive waste at Ward Valley.

PMID- 7569883
TI  - Radioactive waste at Ward Valley.

PMID- 7569885
TI  - Grad school rankings rankle.

PMID- 7569886
TI  - NIH funding. The price of compromise.

PMID- 7569887
TI  - Nobel Prizes. Newspaper backs down over allegations of impropriety.

PMID- 7569888
TI  - AIDS researchers, activists fight crisis in clinical trials.

PMID- 7569889
TI  - Receptors find work as guides.

PMID- 7569890
TI  - Malaria research. Inbred parasites may spur resistance.

PMID- 7569891
TI  - Cell biology. Two major signaling pathways meet at MAP-kinase.

PMID- 7569892
TI  - Acetylcholine receptors: too many channels, too few functions.

PMID- 7569893
TI  - Minisatellites and human disease.

PMID- 7569894
TI  - Vitamin K and energy transduction: a base strength amplification mechanism.
AB  - Energy transfer provides an arrow in the metabolism of living systems. Direct
      energetic coupling of chemical transformations, such that the free energy
      generated in one reaction is channeled to another, is the essence of energy
      transfer, whereas the purpose is the production of high-energy chemical
      intermediates. Vitamin K provides a particularly instructive example of energy
      transfer. A key principle at work in the vitamin K system can be termed "base
      strength amplification." In the base strength amplification sequence, the free
      energy of oxygenation of vitamin K hydroquinone (vitamin KH2) is used to
      transform a weak base to a strong base in order to effect proton removal from
      selected glutamate (Glu) residues in the blood-clotting proteins.

PMID- 7569895
TI  - Nicotine enhancement of fast excitatory synaptic transmission in CNS by
      presynaptic receptors.
AB  - The behavioral and cognitive effects of nicotine suggest that nicotinic
      acetylcholine receptors (nAChRs) participate in central nervous system (CNS)
      function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites
      are common in the brain, there is little evidence for synapses mediated by nAChRs
      in the CNS. To test whether, CNS nAChRs might modify rather than mediate
      transmission, the regulation of excitatory synaptic transmission by these
      receptors was examined. Nanomolar concentrations of nicotine enhanced both
      glutamatergic and cholinergic synaptic transmission by activation of presynaptic
      nAChRs that increased presynaptic [Ca2]i. Pharmacological and subunit deletion
      experiments reveal that these presynaptic nAChRs include the alpha 7 subunit.
      These findings reveal that CNS nAChRs enhance fast excitatory transmission,
      providing a likely mechanism for the complex behavioral effects of nicotine.

PMID- 7569896
TI  - Condensation of methane, ammonia, and water and the inhibition of convection in
      giant planets.
AB  - The condensation of chemical species of high molecular mass such as methane,
      ammonia, and water can inhibit convection in the hydrogen-helium atmospheres of
      the giant planets. Convection is inhibited in Uranus and Neptune when methane
      reaches an abundance of about 15 times the solar value and in Jupiter and Saturn
      if the abundance of water is more than about five times the solar value. The
      temperature gradient consequently becomes superadiabatic, which is observed in
      temperature profiles inferred from radio-occultation measurements. The planetary
      heat flux is then likely to be transported by another mechanism, possibly
      radiation in Uranus, or diffusive convection.

PMID- 7569897
TI  - Mating patterns in malaria parasite populations of Papua New Guinea.
AB  - Description of the genetic structure of malaria parasite populations is central
      to an understanding of the spread of multiple-locus drug and vaccine resistance.
      The Plasmodium falciparum mating patterns from madang, Papua New Guinea, where
      intense transmission of malaria occurs, are described here. A high degree of
      inbreeding occurs in the absence of detectable linkage disequilibrium. This
      contrasts with other studies, indicating that the genetic structure of malaria
      parasite populations is neither clonal nor panmictic but will vary according to
      the transmission characteristics of the region.

PMID- 7569898
TI  - Ethylene insensitivity conferred by Arabidopsis ERS gene.
AB  - ERS (ethylene response sensor), a gene in the Arabidopsis thaliana ethylene
      hormone-response pathway, was uncovered by cross-hybridization with the
      Arabidopsis ETR1 gene. The deduced ERS protein has sequence similarity with the
      amino-terminal domain and putative histidine protein kinase domain of ETR1, but
      it does not have a receiver domain as found in ETR1. A missense mutation
      identical to the dominant etr1-4 mutation was introduced into the ERS gene. The
      altered ERS gene conferred dominant ethylene insensitivity to wild-type
      Arabidopsis. Double-mutant analysis indicates that ERS acts upstream of the CTR1
      protein kinase gene in the ethylene-response pathway.

PMID- 7569901
TI  - Imaging elementary events of calcium release in skeletal muscle cells.
AB  - In skeletal muscle cells, calcium release to trigger contraction occurs at
      triads, specialized junctions where sarcoplasmic reticulum channels are opened by
      voltage sensors in the transverse tubule. Scanning confocal microscopy was used
      in cells under voltage clamp to measure the concentration of intracellular
      calcium, [Ca2+]i, at individual triads and [Ca2+]i gradients that were
      proportional to calcium release. In cells stimulated with small depolarizations,
      the [Ca2+]i gradients broke down into elementary events, corresponding to single
      channel currents of about 0.1 picoampere. Because these events were one-tenth to
      one-fifth the size of calcium sparks (elementary release events of cardiac
      muscle), skeletal muscle control mechanisms appear to be fundamentally different.

PMID- 7569899
TI  - Activation of a G protein complex by aggregation of beta-1,4
      galactosyltransferase on the surface of sperm.
AB  - Fertilization is initiated by the species-specific binding of sperm to the
      extracellular coat of the egg. One sperm receptor for the mouse egg is beta-1,4
      galactosyltransferase (GalTase), which binds O-linked oligosaccharides on the egg
      coat glycoprotein ZP3. ZP3 binding induces acrosomal exocytosis through the
      activation of a pertussis toxin-sensitive heterotrimeric guanine nucleotide
      binding protein (G protein). The cytoplasmic domain of sperm surface GalTase
      bound to and activated a heterotrimeric G protein complex that contained the Gi
      alpha subunit. Aggregation of GalTase by multivalent ligands elicited G protein
      activation. Sperm from transgenic mice that overexpressed GalTase had higher
      rates of G protein activation than did wild-type sperm, which rendered transgenic
      sperm hypersensitive to their ZP3 ligand. Thus, the cytoplasmic domain of cell
      surface GalTase appears to enable it to function as a signal-transducing receptor
      for extracellular oligosaccharide ligands.

PMID- 7569900
TI  - Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon
      beta-stimulated gene expression through STAT proteins.
AB  - Activation of early response genes by interferons (IFNs) requires tyrosine
      phosphorylation of STAT (signal transducers and activators of transcription)
      proteins. It was found that the serine-threonine kinase mitogen-activated protein
      kinase (MAPK) [specifically, the 42-kilodalton MAPK or extracellular signal
      regulated kinase 2 (ERK2)] interacted with the alpha subunit of IFN-alpha/beta
      receptor in vitro and in vivo. Treatment of cells with IFN-beta induced tyrosine
      phosphorylation and activation of MAPK and caused MAPK and Stat1 alpha to
      coimmunoprecipitate. Furthermore, expression of dominant negative MAPK inhibited
      IFN-beta-induced transcription. Therefore, MAPK appears to regulate IFN-alpha and
      IFN-beta activation of early response genes by modifying the Jak-STAT signaling
      cascade.

PMID- 7569902
TI  - Activation of dual T cell signaling pathways by the chemokine RANTES.
AB  - The chemokine RANTES induced biphasic mobilization of Ca2+ in T cells. The
      initial peak, a transient increase in cytosolic Ca2+ mediated by a heterotrimeric
      guanine nucleotide-binding protein (G protein)--coupled pathway, was associated
      predominantly with chemotaxis. The second peak, Ca2+ release and sustained influx
      dependent on protein tyrosine kinases, was associated with a spectrum of cellular
      responses--Ca2+ channel opening, interleukin-2 receptor expression, cytokine
      release, and T cell proliferation--characteristic of T cell receptor activation.
      Other chemokines did not produce these responses. Thus, in addition to inducing
      chemotaxis, RANTES can act as an antigen-independent activator of T cells in
      vitro.

PMID- 7569903
TI  - Regulation of hippocampal transmitter release during development and long-term
      potentiation.
AB  - Developmental changes in rat hippocampal transmitter release and synaptic
      plasticity were investigated. Recordings from pairs of pyramidal neurons in
      slices showed that an action potential in a CA3 neuron released only a single
      quantum of transmitter onto a CA1 neuron. Failures of synaptic transmission
      reflected probabilistic transmitter release. The probability of release (Pr) was
      0.9 in 4- to 8-day-old rats and decreased to less than 0.5 at 2 to 3 weeks. Long
      term potentiation (LTP) in 2- to 3-week-old rats was associated with an increase
      in Pr from a single synaptic site. The high initial Pr in 4- to 8-day-old rats
      normally occludes the expression of LTP at this stage.

PMID- 7569904
TI  - Regulated subcellular distribution of the NR1 subunit of the NMDA receptor.
AB  - NMDA (N-methyl-D-aspartate) receptors are selectively localized at the
      postsynaptic membrane of excitatory synapses in the mammalian brain. The
      molecular mechanisms underlying this localization were investigated by expressing
      the NR1 subunit of the NMDA receptor in fibroblasts. NR1 splice variants
      containing the first COOH-terminal exon cassette (NR1A and NR1D) were located in
      discrete, receptor-rich domains associated with the plasma membrane. NR1 splice
      variants lacking this exon cassette (NR1C and NR1E) were distributed throughout
      the cell, with large amounts of NR1 protein present in the cell interior.
      Insertion of this exon cassette into the COOH-terminus of the GluR1 AMPA (alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor was sufficient to cause
      GluR1 to be localized to discrete, receptor-rich domains. Furthermore, protein
      kinase C phosphorylation of specific serines within this exon disrupted the
      receptor-rich domains. These results demonstrate that amino acid sequences
      contained within the NR1 molecule serve to localize this receptor subunit to
      discrete membrane domains in a manner that is regulated by alternative splicing
      and protein phosphorylation.

PMID- 7569907
TI  - The Endangered Species Act.

PMID- 7569908
TI  - Pioneering work.

PMID- 7569906
TI  - Science in the stationary phase.

PMID- 7569905
TI  - Domain interaction between NMDA receptor subunits and the postsynaptic density
      protein PSD-95.
AB  - The N-methyl-D-aspartate (NMDA) receptor subserves synaptic glutamate-induced
      transmission and plasticity in central neurons. The yeast two-hybrid system was
      used to show that the cytoplasmic tails of NMDA receptor subunits interact with a
      prominent postsynaptic density protein PSD-95. The second PDZ domain in PSD-95
      binds to the seven-amino acid, COOH-terminal domain containing the terminal tSXV
      motif (where S is serine, X is any amino acid, and V is valine) common to NR2
      subunits and certain NR1 splice forms. Transcripts encoding PSD-95 are expressed
      in a pattern similar to that of NMDA receptors, and the NR2B subunit co-localizes
      with PSD-95 in cultured rat hippocampal neurons. The interaction of these
      proteins may affect the plasticity of excitatory synapses.

PMID- 7569909
TI  - Conflict marks crime conference.

PMID- 7569910
TI  - Commission proposes new definition of misconduct.

PMID- 7569911
TI  - International experts help probe Haiti's bloody past.

PMID- 7569913
TI  - Another blow weakens EMF-cancer link.

PMID- 7569912
TI  - Chambon builds institute with U.S. funds and eye for detail.

PMID- 7569914
TI  - Potential animal model for AIDS.

PMID- 7569915
TI  - Tracing how the sexes develop.

PMID- 7569916
TI  - Snaring the genes that divide the sexes for mammals.

PMID- 7569917
TI  - How males and females achieve X equality.

PMID- 7569919
TI  - Baculovirus bounty.

PMID- 7569918
TI  - Tuning into better catalysts.

PMID- 7569922
TI  - Understanding C-H bond oxidations: H. and H- transfer in the oxidation of toluene
      by permanganate.
AB  - The oxidation of toluene by permanganate has been studied as a model for the
      oxidation of C-H bonds by metal reagents, metalloenzymes, and metal oxide
      surfaces. In water, the reaction proceeds by hydride (H-) transfer from toluene
      to a permanganate oxygen, whereas in toluene solution, permanganate abstracts a
      hydrogen atom (H.). The ability of permanganate to abstract a hydrogen atom is
      rationalized on the basis of the strong O-H bond formed on H. addition to
      permanganate. This approach allows understanding and prediction of the rates of
      hydrogen atom transfer from substrates to metal active sites.

PMID- 7569923
TI  - Global distribution of persistent organochlorine compounds.
AB  - The global distribution of 22 potentially harmful organochlorine compounds was
      investigated in more than 200 tree bark samples from 90 sites worldwide. High
      concentrations of organochlorines were found not only in some developing
      countries but also in industrialized countries, which continue to be highly
      contaminated even though the use of many of these compounds is restricted. The
      distribution of relatively volatile organochlorine compounds (such as
      hexachlorobenzene) is dependent on latitude and demonstrates the global
      distillation effect, whereas less volatile organochlorine compounds (such as
      endosulfan) are not as effectively distilled and tend to remain in the region of
      use.

PMID- 7569921
TI  - Hemoglobin allostery: resonance Raman spectroscopy of kinetic intermediates.
AB  - The end states, R and T, of the allosteric transition in hemoglobin (Hb) are
      structurally well characterized, but there is little information on intermediate
      structures along the allosteric pathway. These intermediates were examined by
      means of time-resolved resonance Raman spectroscopy in the nanosecond-to
      microsecond interval after HbCO photolysis. Complementary spectra of the heme
      group and of the tyrosine and tryptophan residues were recorded during laser
      excitation at 436 and 230 nanometers. These spectra reveal a sequence of
      interleaved tertiary and quaternary motions during the photocycle, motions
      involving the proximal and distal helices, and the alpha 1 beta 2 subunit
      interface. This sequence leads to a modified form of the T state, in which the
      alpha 1 beta 2 interface is deformed as a result of two carbon monoxide molecules
      binding to the same dimer within the tetramer.

PMID- 7569924
TI  - Magnetic resonance elastography by direct visualization of propagating acoustic
      strain waves.
AB  - A nuclear magnetic resonance imaging (MRI) method is presented for quantitatively
      mapping the physical response of a material to harmonic mechanical excitation.
      The resulting images allow calculation of regional mechanical properties.
      Measurements of shear modulus obtained with the MRI technique in gel materials
      correlate with independent measurements of static shear modulus. The results
      indicate that displacement patterns corresponding to cyclic displacements smaller
      than 200 nanometers can be measured. The findings suggest the feasibility of a
      medical imaging technique for delineating elasticity and other mechanical
      properties of tissue.

PMID- 7569920
TI  - From molecular diversity to catalysis: lessons from the immune system.
AB  - By combining the enormous molecular diversity of the immune system with basic
      mechanistic principles of chemistry, one can produce catalytic antibodies that
      allow control of reactions in ways heretofore not possible. Mechanistic and
      structural studies of these antibodies are also providing insights into important
      aspects of enzymatic catalysis and the evolution of catalytic function. Moreover,
      the ability to rationally direct the immune response to generate selective
      catalysts for reactions ranging from pericyclic and redox reactions to cationic
      rearrangement reactions underscores the chemical potential of this and other
      large combinatorial libraries.

PMID- 7569925
TI  - Circadian oscillations of cytosolic and chloroplastic free calcium in plants.
AB  - Tobacco and Arabidopsis plants, expressing a transgene for the calcium-sensitive
      luminescent protein apoaequorin, revealed circadian oscillations in free
      cytosolic calcium that can be phase-shifted by light-dark signals. When
      apoaequorin was targeted to the chloroplast, circadian chloroplast calcium
      rhythms were likewise observed after transfer of the seedlings to constant
      darkness. Circadian oscillations in free calcium concentrations can be expected
      to control many calcium-dependent enzymes and processes accounting for circadian
      outputs. Regulation of calcium flux is therefore fundamental to the organization
      of circadian systems.

PMID- 7569927
TI  - A specialized pathway affecting virulence glycoconjugates of Leishmania.
AB  - For virulence and transmission, the protozoan parasite Leishmania must assemble a
      complex glycolipid on the cell surface, the lipophosphoglycan (LPG). Functional
      complementation identified the gene LPG2, which encodes an integral Golgi
      membrane protein implicated in intracellular compartmentalization of LPG
      biosynthesis. Ipg2- mutants lack only characteristic disaccharide-phosphate
      repeats, normally present on both LPG and other surface or secreted molecules
      considered critical for infectivity. In contrast, a related yeast gene,
      VAN2/VRG4, is essential and required for general Golgi function. These results
      suggest that LPG2 participates in a specialized virulence pathway, which may
      offer an attractive target for chemotherapy.

PMID- 7569926
TI  - Modulation of transcription factor Ets-1 DNA binding: DNA-induced unfolding of an
      alpha helix.
AB  - Conformational changes, including local protein folding, play important roles in
      protein-DNA interactions. Here, studies of the transcription factor Ets-1
      provided evidence that local protein unfolding also can accompany DNA binding.
      Circular dichroism and partial proteolysis showed that the secondary structure of
      the Ets-1 DNA-binding domain is unchanged in the presence of DNA. In contrast,
      DNA allosterically induced the unfolding of an alpha helix that lies within a
      flanking region involved in the negative regulation of DNA binding. These
      findings suggest a structural basis for the intramolecular inhibition of DNA
      binding and a mechanism for the cooperative partnerships that are common features
      of many eukaryotic transcription factors.

PMID- 7569929
TI  - Jak-STAT signaling induced by the v-abl oncogene.
AB  - The effect of the v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) on
      the Jak-STAT pathway of cytokine signal transduction was investigated. In murine
      pre-B lymphocytes transformed with A-MuLV, the Janus kinases (Jaks) Jak1 and Jak3
      exhibited constitutive tyrosine kinase activity, and the STAT proteins (signal
      transducers and activators of transcription) normally activated by interleukin-4
      and interleukin-7 were tyrosine-phosphorylated in the absence of these cytokines.
      Coimmunoprecipitation experiments revealed that in these cells v-Abl was
      physically associated with Jak1 and Jak3. Inactivation of v-Abl tyrosine kinase
      in a pre-B cell line transformed with a temperature-sensitive mutant of v-abl
      resulted in abrogation of constitutive Jak-STAT signaling. A direct link may
      exist between transformation by v-abl and cytokine signal transduction.

PMID- 7569928
TI  - Interaction of tyrosine-based sorting signals with clathrin-associated proteins.
AB  - Tyrosine-based signals within the cytoplasmic domain of integral membrane
      proteins mediate clathrin-dependent protein sorting in the endocytic and
      secretory pathways. A yeast two-hybrid system was used to identify proteins that
      bind to tyrosine-based signals. The medium chains (mu 1 and mu 2) of two clathrin
      associated protein complexes (AP-1 and AP-2, respectively) specifically
      interacted with tyrosine-based signals of several integral membrane proteins. The
      interaction was confirmed by in vitro binding assays. Thus, it is likely that the
      medium chains serve as signal-binding components of the clathrin-dependent
      sorting machinery.

PMID- 7569930
TI  - Lateral interactions in primary visual cortex: a model bridging physiology and
      psychophysics.
AB  - Recent physiological studies show that the spatial context of visual stimuli
      enhances the response of cells in primary visual cortex to weak stimuli and
      suppresses the response to strong stimuli. A model of orientation-tuned neurons
      was constructed to explore the role of lateral cortical connections in this dual
      effect. The differential effect of excitatory and inhibitory current and noise
      conveyed by the lateral connections explains the physiological results as well as
      the psychophysics of pop-out and contour completion. Exploiting the model's
      property of stochastic resonance, the visual context changes the model's
      intrinsic input variability to enhance the detection of weak signals.

PMID- 7569931
TI  - An internal model for sensorimotor integration.
AB  - On the basis of computational studies it has been proposed that the central
      nervous system internally simulates the dynamic behavior of the motor system in
      planning, control, and learning; the existence and use of such an internal model
      is still under debate. A sensorimotor integration task was investigated in which
      participants estimated the location of one of their hands at the end of movements
      made in the dark and under externally imposed forces. The temporal propagation of
      errors in this task was analyzed within the theoretical framework of optimal
      state estimation. These results provide direct support for the existence of an
      internal model.

PMID- 7569932
TI  - FFA-1, a protein that promotes the formation of replication centers within
      nuclei.
AB  - In the nuclei of eukaryotic cells, initiation of DNA replication occurs at a
      discrete number of foci. One component of these foci is the DNA replication
      factor RP-A. Here, the process leading to the association of RP-A with foci was
      reconstituted with cytosolic fractions derived from Xenopus eggs. With the use of
      this fractionated system, a 170-kilodalton protein required for the assembly of
      RP-A into foci was identified and purified. The protein appears to be an integral
      component of the foci at which replication of DNA is initiated in eukaryotic
      nuclei.

PMID- 7569933
TI  - Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35.
AB  - The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of
      human interleukin-1 beta converting enzyme (ICE) and three of its homologs in
      enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of
      ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of
      enzymatic activity correlated with the cleavage of p35 and the formation of a
      stable ICE-p35 complex. The ability of p35 to block apoptosis in different
      pathways and in distantly related organisms suggests a central and conserved role
      for ICE-like proteases in the induction of apoptosis.

PMID- 7569934
TI  - Discrete cortical regions associated with knowledge of color and knowledge of
      action.
AB  - The areas of the brain that mediate knowledge about objects were investigated by
      measuring changes in regional cerebral blood flow (rCBF) using positron emission
      tomography (PET). Subjects generated words denoting colors and actions associated
      with static, achromatic line drawings of objects in one experiment, and with the
      written names of objects in a second experiment. In both studies, generation of
      color words selectively activated a region in the ventral temporal lobe just
      anterior to the area involved in the perception of color, whereas generation of
      action words activated a region in the middle temporal gyrus just anterior to the
      area involved in the perception of motion. These data suggest that object
      knowledge is organized as a distributed system in which the attributes of an
      object are stored close to the regions of the cortex that mediate perception of
      those attributes.

PMID- 7569936
TI  - Careers '95: the future of the Ph.D.

PMID- 7569937
TI  - Faltering press embargo?

PMID- 7569938
TI  - Faltering press embargo?

PMID- 7569940
TI  - Data on the web?

PMID- 7569939
TI  - Faltering press embargo?

PMID- 7569935
TI  - Dependence of peptide binding by MHC class I molecules on their interaction with
      TAP.
AB  - Major histocompatibility complex (MHC) class I molecules bind peptides that are
      delivered from the cytosol into the endoplasmic reticulum by the MHC-encoded
      transporter associated with antigen processing (TAP). Peptide capture by immature
      heterodimers of class I heavy chains and beta 2-microglobulin may be facilitated
      by their physical association with TAP. A genetic defect in a human mutant cell
      line causes the complete failure of diverse class I heterodimers to associate
      with TAP. This deficiency impairs the ability of the class I heterodimers to
      efficiently capture peptides and results from loss of function of an unidentified
      gene or genes linked to the MHC.

PMID- 7569941
TI  - Lights, camera ... and action!

PMID- 7569942
TI  - Kaposi's sarcoma findings.

PMID- 7569943
TI  - Paving the info superhighway.

PMID- 7569944
TI  - Cockroach immunity.

PMID- 7569945
TI  - Panel faults research consent process.

PMID- 7569946
TI  - Waivers proposed for emergency studies.

PMID- 7569947
TI  - Differences in HIV strains may underlie disease patterns.

PMID- 7569948
TI  - Confirmation for combination AIDS therapy.

PMID- 7569949
TI  - PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints.

PMID- 7569950
TI  - Religion and gene patenting.

PMID- 7569951
TI  - Plio-Pleistocene African climate.
AB  - Marine records of African climate variability document a shift toward more arid
      conditions after 2.8 million years ago (Ma), evidently resulting from remote
      forcing by cold North Atlantic sea-surface temperatures associated with the onset
      of Northern Hemisphere glacial cycles. African climate before 2.8 Ma was
      regulated by low-latitude insolation forcing of monsoonal climate due to Earth
      orbital precession. Major steps in the evolution of African hominids and other
      vertebrates are coincident with shifts to more arid, open conditions near 2.8 Ma,
      1.7 Ma, and 1.0 Ma, suggesting that some Pliocene (Plio)-Pleistocene speciation
      events may have been climatically mediated.

PMID- 7569952
TI  - Sulfite reductase structure at 1.6 A: evolution and catalysis for reduction of
      inorganic anions.
AB  - Fundamental chemical transformations for biogeochemical cycling of sulfur and
      nitrogen are catalyzed by sulfite and nitrite reductases. The crystallographic
      structure of Escherichia coli sulfite reductase hemoprotein (SiRHP), which
      catalyzes the concerted six-electron reductions of sulfite to sulfide and nitrite
      to ammonia, was solved with multiwavelength anomalous diffraction (MAD) of the
      native siroheme and Fe4S4 cluster cofactors, multiple isomorphous replacement,
      and selenomethionine sequence markers. Twofold symmetry within the 64-kilodalton
      polypeptide generates a distinctive three-domain alpha/beta fold that controls
      cofactor assembly and reactivity. Homology regions conserved between the symmetry
      related halves of SiRHP and among other sulfite and nitrite reductases revealed
      key residues for stability and function, and identified a sulfite or nitrite
      reductase repeat (SNiRR) common to a redox-enzyme superfamily. The saddle-shaped
      siroheme shares a cysteine thiolate ligand with the Fe4S4 cluster and ligates an
      unexpected phosphate anion. In the substrate complex, sulfite displaces phosphate
      and binds to siroheme iron through sulfur. An extensive hydrogen-bonding network
      of positive side chains, water molecules, and siroheme carboxylates activates S-O
      bonds for reductive cleavage.

PMID- 7569953
TI  - Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both
      threonine-14 and tyrosine-15.
AB  - Cdc2 is the cyclin-dependent kinase that controls entry of cells into mitosis.
      Phosphorylation of Cdc2 on threonine-14 and tyrosine-15 inhibits the activity of
      the enzyme and prevents premature initiation of mitosis. Although Wee1 has been
      identified as the kinase that phosphorylates tyrosine-15 in various organisms,
      the threonine-14-specific kinase has not been isolated. A complementary DNA was
      cloned from Xenopus that encodes Myt1, a member of the Wee1 family that was
      discovered to phosphorylate Cdc2 efficiently on both threonine-14 and tyrosine
      15. Myt1 is a membrane-associated protein that contains a putative transmembrane
      segment. Immunodepletion studies suggested that Myt1 is the predominant threonine
      14-specific kinase in Xenopus egg extracts. Myt1 activity is highly regulated
      during the cell cycle, suggesting that this relative of Wee1 plays a role in
      mitotic control.

PMID- 7569954
TI  - Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting
      phosphatase KAP in the absence of cyclin.
AB  - The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of
      a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Human KAP
      (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate
      Thr160 in human Cdk2. KAP was unable to dephosphorylate Tyr15 and only
      dephosphorylated Thr160 in native monomeric Cdk2. The binding of cyclin A to Cdk2
      inhibited the dephosphorylation of Thr160 by KAP but did not preclude the binding
      of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr160 by
      KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A.
      These results suggest that KAP binds to Cdk2 and dephosphorylates Thr160 when the
      associated cyclin subunit is degraded or dissociates.

PMID- 7569955
TI  - Prion-inducing domain of yeast Ure2p and protease resistance of Ure2p in prion
      containing cells.
AB  - The genetic properties of the [URE3] non-Mendelian element of Saccharomyces
      cerevisiae suggest that it is a prion (infectious protein) form of Ure2p, a
      regulator of nitrogen catabolism. In extracts from [URE3] strains, Ure2p was
      partially resistant to proteinase K compared with Ure2p from wild-type extracts.
      Overexpression of Ure2p in wild-type strains induced a 20- to 200-fold increase
      in the frequency with which [URE3] arose. Overexpression of just the amino
      terminal 65 residues of Ure2p increased the frequency of [URE3] induction 6000
      fold. Without this "prion-inducing domain" the carboxyl-terminal domain performed
      the nitrogen regulation function of Ure2p, but could not be changed to the [URE3]
      prion state. Thus, this domain induced the prion state in trans, whereas in cis
      it conferred susceptibility of the adjoining nitrogen regulatory domain to prion
      infections.

PMID- 7569958
TI  - Flaws in risk assessments.

PMID- 7569959
TI  - Dioxins in Vietnam.

PMID- 7569957
TI  - Dissociation of synchronization and excitability in furosemide blockade of
      epileptiform activity.
AB  - Furosemide, a chloride cotransport inhibitor, reversibly blocked synchronized
      burst discharges in hippocampal slices without reducing the pyramidal cell
      response to single electrical stimuli. Images of the intrinsic optical signal
      acquired during these slice experiments indicated that furosemide coincidentally
      blocked changes in extracellular space. In urethane-anesthetized rats,
      systemically injected furosemide blocked kainic acid-induced electrical
      discharges recorded from cortex. These results suggest that (i) neuronal
      synchronization involved in epileptiform activity can be dissociated from
      synaptic excitability; (ii) nonsynaptic mechanisms, possibly associated with
      furosemide-sensitive cell volume regulation, may be critical for synchronization
      of neuronal activity; and (iii) agents that affect extracellular volume may have
      clinical utility as antiepileptic drugs.

PMID- 7569956
TI  - Bax-deficient mice with lymphoid hyperplasia and male germ cell death.
AB  - BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in
      gain-of-function experiments. A Bax knockout mouse was generated that proved
      viable but displayed lineage-specific aberrations in cell death. Thymocytes and B
      cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained
      unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient
      males were infertile as a result of disordered seminiferous tubules with an
      accumulation of atypical premeiotic germ cells, but no mature haploid sperm.
      Multinucleated giant cells and dysplastic cells accompanied massive cell death.
      Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the
      cellular context.

PMID- 7569960
TI  - Electronic publishing.

PMID- 7569961
TI  - Electronic publishing.

PMID- 7569962
TI  - Electronic publishing.

PMID- 7569963
TI  - Asymmetrical ability.

PMID- 7569965
TI  - Chimp finally shows AIDS symptoms.

PMID- 7569964
TI  - CO binding and bending energetics.

PMID- 7569966
TI  - Yellowstone managers stake a claim on hot-springs microbes.

PMID- 7569967
TI  - Lyme disease. NIH gears up to test a hotly disputed theory.

PMID- 7569968
TI  - Designer tissues take hold.

PMID- 7569969
TI  - How the glucocorticoids suppress immunity.

PMID- 7569970
TI  - New ways to avoid organ rejection buoy hopes.

PMID- 7569971
TI  - Titanic protein gives muscles structure and bounce.

PMID- 7569972
TI  - A heterodimeric transcriptional repressor becomes crystal clear.

PMID- 7569973
TI  - Unity in transposition reactions.

PMID- 7569974
TI  - Crystal structure of the MATa1/MAT alpha 2 homeodomain heterodimer bound to DNA.
AB  - The Saccharomyces cerevisiae MATa1 and MAT alpha 2 homeodomain proteins, which
      play a role in determining yeast cell type, form a heterodimer that binds DNA and
      represses transcription in a cell type-specific manner. Whereas the alpha 2 and
      a1 proteins on their own have only modest affinity for DNA, the a1/alpha 2
      heterodimer binds DNA with high specificity and affinity. The three-dimensional
      crystal structure of the a1/alpha 2 homeodomain heterodimer bound to DNA was
      determined at a resolution of 2.5 A. The a1 and alpha 2 homeodomains bind in a
      head-to-tail orientation, with heterodimer contacts mediated by a 16-residue tail
      located carboxyl-terminal to the alpha 2 homeodomain. This tail becomes ordered
      in the presence of a1, part of it forming a short amphipathic helix that packs
      against the a1 homeodomain between helices 1 and 2. A pronounced 60 degree bend
      is induced in the DNA, which makes possible protein-protein and protein-DNA
      contacts that could not take place in a straight DNA fragment. Complex formation
      mediated by flexible protein-recognition peptides attached to stably folded DNA
      binding domains may prove to be a general feature of the architecture of other
      classes of eukaryotic transcriptional regulators.

PMID- 7569975
TI  - Role of transcriptional activation of I kappa B alpha in mediation of
      immunosuppression by glucocorticoids.
AB  - Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly
      understood. Nuclear factor kappa B (NF-kappa B), a regulator of immune system and
      inflammation genes, may be a target for glucocorticoid-mediated
      immunosuppression. The activation of NF-kappa B involves the targeted degradation
      of its cytoplasmic inhibitor, I kappa B alpha, and the translocation of NF-kappa
      B to the nucleus. Here it is shown that the synthetic glucocorticoid
      dexamethasone induces the transcription of the I kappa B alpha gene, which
      results in an increased rate of I kappa B alpha protein synthesis. Stimulation by
      tumor necrosis factor causes the release of NF-kappa B from I kappa B alpha.
      However, in the presence of dexamethasone this newly released NF-kappa B quickly
      reassociates with newly synthesized I kappa B alpha, thus markedly reducing the
      amount of NF-kappa B that translocates to the nucleus. This decrease in nuclear
      NF-kappa B is predicted to markedly decrease cytokine secretion and thus
      effectively block the activation of the immune system.

PMID- 7569976
TI  - Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through
      induction of I kappa B synthesis.
AB  - Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive
      agents. They inhibit synthesis of almost all known cytokines and of several cell
      surface molecules required for immune function, but the mechanism underlying this
      activity has been unclear. Here it is shown that glucocorticoids are potent
      inhibitors of nuclear factor kappa B (NF-kappa B) activation in mice and cultured
      cells. This inhibition is mediated by induction of the I kappa B alpha inhibitory
      protein, which traps activated NF-kappa B in inactive cytoplasmic complexes.
      Because NF-kappa B activates many immunoregulatory genes in response to pro
      inflammatory stimuli, the inhibition of its activity can be a major component of
      the anti-inflammatory activity of glucocorticoids.

PMID- 7569977
TI  - Altered DNA recognition and bending by insertions in the alpha 2 tail of the
      yeast a1/alpha 2 homeodomain heterodimer.
AB  - The yeast MAT alpha 2 and MATa1 homeodomain proteins bind cooperatively as a
      heterodimer to sites upstream of haploid-specific genes, repressing their
      transcription. In the crystal structure of alpha 2 and a1 bound to DNA, each
      homeodomain makes independent base-specific contacts with the DNA and the two
      proteins contact each other through an extended tail region of alpha 2 that
      tethers the two homeodomains to one another. Because this extended region may be
      flexible, the ability of the heterodimer to discriminate among DNA sites with
      altered spacing between alpha 2 and a1 binding sites was examined. Spacing
      between the half sites was critical for specific DNA binding and transcriptional
      repression by the complex. However, amino acid insertions in the tail region of
      alpha 2 suppressed the effect of altering an a1/alpha 2 site by increasing the
      spacing between the half sites. Insertions in the tail also decreased DNA bending
      by a1/alpha 2. Thus tethering the two homeodomains contributes to DNA bending by
      a1/alpha 2, but the precise nature of the resulting bend is not essential for
      repression.

PMID- 7569978
TI  - Titins: giant proteins in charge of muscle ultrastructure and elasticity.
AB  - In addition to thick and thin filaments, vertebrate striated muscle contains a
      third filament system formed by the giant protein titin. Single titin molecules
      extend from Z discs to M lines and are longer than 1 micrometer. The titin
      filament contributes to muscle assembly and resting tension, but more details are
      not known because of the large size of the protein. The complete complementary
      DNA sequence of human cardiac titin was determined. The 82-kilobase complementary
      DNA predicts a 3-megadalton protein composed of 244 copies of immunoglobulin and
      fibronectin type III (FN3) domains. The architecture of sequences in the A band
      region of titin suggests why thick filament structure is conserved among
      vertebrates. In the I band region, comparison of titin sequences from muscles of
      different passive tension identifies two elements that correlate with tissue
      stiffness. This suggests that titin may act as two springs in series. The
      differential expression of the springs provides a molecular explanation for the
      diversity of sarcomere length and resting tension in vertebrate striated muscles.

PMID- 7569979
TI  - Requirement for generation of H2O2 for platelet-derived growth factor signal
      transduction.
AB  - Stimulation of rat vascular smooth muscle cells (VSMCs) by platelet-derived
      growth factor (PDGF) transiently increased the intracellular concentration of
      hydrogen peroxide (H2O2). This increase could be blunted by increasing the
      intracellular concentration of the scavenging enzyme catalase or by the chemical
      antioxidant N-acetylcysteine. The response of VSMCs to PDGF, which includes
      tyrosine phosphorylation, mitogen-activated protein kinase stimulation, DNA
      synthesis, and chemotaxis, was inhibited when the growth factor-stimulated rise
      in H2O2 concentration was blocked. These results suggest that H2O2 may act as a
      signal-transducing molecule, and they suggest a potential mechanism for the
      cardioprotective effects of antioxidants.

PMID- 7569980
TI  - Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunization.
AB  - Direct inoculation of DNA, in the form of purified bacterial plasmids that are
      unable to replicate in mammalian cells but are able to direct cell synthesis of
      foreign proteins, is being explored as an approach to vaccine development. Here,
      a highly attenuated Shigella vector invaded mammalian cells and delivered such
      plasmids into the cytoplasm of cells, and subsequent production of functional
      foreign protein was measured. Because this Shigella vector was designed to
      deliver DNA to colonic mucosa, the method is a potential basis for oral and other
      mucosal DNA immunization and gene therapy strategies.

PMID- 7569981
TI  - Speech recognition with primarily temporal cues.
AB  - Nearly perfect speech recognition was observed under conditions of greatly
      reduced spectral information. Temporal envelopes of speech were extracted from
      broad frequency bands and were used to modulate noises of the same bandwidths.
      This manipulation preserved temporal envelope cues in each band but restricted
      the listener to severely degraded information on the distribution of spectral
      energy. The identification of consonants, vowels, and words in simple sentences
      improved markedly as the number of bands increased; high speech recognition
      performance was obtained with only three bands of modulated noise. Thus, the
      presentation of a dynamic temporal pattern in only a few broad spectral regions
      is sufficient for the recognition of speech.

PMID- 7569982
TI  - Increased cortical representation of the fingers of the left hand in string
      players.
AB  - Magnetic source imaging revealed that the cortical representation of the digits
      of the left hand of string players was larger than that in controls. The effect
      was smallest for the left thumb, and no such differences were observed for the
      representations of the right hand digits. The amount of cortical reorganization
      in the representation of the fingering digits was correlated with the age at
      which the person had begun to play. These results suggest that the representation
      of different parts of the body in the primary somatosensory cortex of humans
      depends on use and changes to conform to the current needs and experiences of the
      individual.

PMID- 7569984
TI  - Industry, academia, and the Nobel Prize.

PMID- 7569986
TI  - Aggression in mice and men?

PMID- 7569983
TI  - In transition.

PMID- 7569985
TI  - Industry, academia and the Nobel Prize.

PMID- 7569987
TI  - Women, math, and test scores.

PMID- 7569989
TI  - From genome to proteome: looking at a cell's proteins.

PMID- 7569990
TI  - Nobel prizes: fly development work bears prize-winning fruit.

PMID- 7569988
TI  - Entering the postgenome era.

PMID- 7569991
TI  - Genetic discrimination and health insurance: an urgent need for reform.

PMID- 7569992
TI  - A time to sequence.

PMID- 7569994
TI  - Transfer of genes to humans: early lessons and obstacles to success.
AB  - Enough information has been gained from clinical trials to allow the conclusion
      that human gene transfer is feasible, can evoke biologic responses that are
      relevant to human disease, and can provide important insights into human biology.
      Adverse events have been uncommon and have been related to the gene delivery
      strategies, not to the genetic material being transferred. Human gene transfer
      still faces significant hurdles before it becomes an established therapeutic
      strategy. However, its accomplishments to date are impressive, and the logic of
      the potential usefulness of this clinical paradigm continues to be compelling.

PMID- 7569995
TI  - The nematode Caenorhabditis elegans and its genome.
AB  - Over the past two decades, the small soil nematode Caenorhabditis elegans has
      become established as a major model system for the study of a great variety of
      problems in biology and medicine. One of its most significant advantages is its
      simplicity, both in anatomy and in genomic organization. The entire haploid
      genetic content amounts to 100 million base pairs of DNA, about 1/30 the size of
      the human value. As a result, C. elegans has also provided a pilot system for the
      construction of physical maps of larger animal and plant genomes, and
      subsequently for the complete sequencing of those genomes. By mid-1995,
      approximately one-fifth of the complete DNA sequence of this animal had been
      determined. Caenorhabditis elegans provides a test bed not only for the
      development and application of mapping and sequencing technologies, but also for
      the interpretation and use of complete sequence information. This article reviews
      the progress so far toward a realizable goal--the total description of the genome
      of a simple animal.

PMID- 7569996
TI  - Genome maps. VI. Caenorhabditis elegans. Wall chart.

PMID- 7569993
TI  - The minimal gene complement of Mycoplasma genitalium.
AB  - The complete nucleotide sequence (580,070 base pairs) of the Mycoplasma
      genitalium genome, the smallest known genome of any free-living organism, has
      been determined by whole-genome random sequencing and assembly. A total of only
      470 predicted coding regions were identified that include genes required for DNA
      replication, transcription and translation, DNA repair, cellular transport, and
      energy metabolism. Comparison of this genome to that of Haemophilus influenzae
      suggests that differences in genome content are reflected as profound differences
      in physiology and metabolic capacity between these two organisms.

PMID- 7569997
TI  - Life with 482 genes.

PMID- 7569998
TI  - Role of yeast insulin-degrading enzyme homologs in propheromone processing and
      bud site selection.
AB  - The Saccharomyces cerevisiae AXL1 gene product Axl1p shares homology with the
      insulin-degrading enzyme family of endoproteases. Yeast axl1 mutants showed a
      defect in a-factor pheromone secretion, and a probable site of processing by
      Axl1p was identified within the a-factor precursor. In addition, Axl1p appears to
      function as a morphogenetic determinant for axial bud site selection. Amino acid
      substitutions within the presumptive active site of Axl1p caused defects in
      propheromone processing but failed to perturb bud site selection. Thus, Axl1p has
      been shown to participate in the dual regulation of distinct signaling pathways,
      and a member of the insulinase family has been implicated in propeptide
      processing.

PMID- 7569999
TI  - Quantitative monitoring of gene expression patterns with a complementary DNA
      microarray.
AB  - A high-capacity system was developed to monitor the expression of many genes in
      parallel. Microarrays prepared by high-speed robotic printing of complementary
      DNAs on glass were used for quantitative expression measurements of the
      corresponding genes. Because of the small format and high density of the arrays,
      hybridization volumes of 2 microliters could be used that enabled detection of
      rare transcripts in probe mixtures derived from 2 micrograms of total cellular
      messenger RNA. Differential expression measurements of 45 Arabidopsis genes were
      made by means of simultaneous, two-color fluorescence hybridization.

PMID- 7570000
TI  - Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-
      immunodeficient patients.
AB  - Adenosine deaminase (ADA) deficiency results in severe combined immunodeficiency,
      the first genetic disorder treated by gene therapy. Two different retroviral
      vectors were used to transfer ex vivo the human ADA minigene into bone marrow
      cells and peripheral blood lymphocytes from two patients undergoing exogenous
      enzyme replacement therapy. After 2 years of treatment, long-term survival of T
      and B lymphocytes, marrow cells, and granulocytes expressing the transferred ADA
      gene was demonstrated and resulted in normalization of the immune repertoire and
      restoration of cellular and humoral immunity. After discontinuation of treatment,
      T lymphocytes, derived from transduced peripheral blood lymphocytes, were
      progressively replaced by marrow-derived T cells in both patients. These results
      indicate successful gene transfer into long-lasting progenitor cells, producing a
      functional multilineage progeny.

PMID- 7570001
TI  - T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4
      years.
AB  - In 1990, a clinical trial was started using retroviral-mediated transfer of the
      adenosine deaminase (ADA) gene into the T cells of two children with severe
      combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as
      did many cellular and humoral immune responses. Gene treatment ended after 2
      years, but integrated vector and ADA gene expression in T cells persisted.
      Although many components remain to be perfected, it is concluded here that gene
      therapy can be a safe and effective addition to treatment for some patients with
      this severe immunodeficiency disease.

PMID- 7570002
TI  - Physical map and organization of Arabidopsis thaliana chromosome 4.
AB  - A physical map of Arabidopsis thaliana chromosome 4 was constructed in yeast
      artificial chromosome clones and used to analyze the organization of the
      chromosome. Mapping of the nucleolar organizing region and the centromere
      integrated the physical and cytogenetic maps. Detailed comparison of physical
      with genetic distances showed that the frequency of recombination varied
      substantially, with relative hot and cold spots occurring along the whole
      chromosome. Eight repeated DNA sequence families were found in a complex
      arrangement across the centromeric region and nowhere else on the chromosome.

PMID- 7570004
TI  - The radius of gyration of an apomyoglobin folding intermediate.

PMID- 7570003
TI  - Serial analysis of gene expression.
AB  - The characteristics of an organism are determined by the genes expressed within
      it. A method was developed, called serial analysis of gene expression (SAGE),
      that allows the quantitative and simultaneous analysis of a large number of
      transcripts. To demonstrate this strategy, short diagnostic sequence tags were
      isolated from pancreas, concatenated, and cloned. Manual sequencing of 1000 tags
      revealed a gene expression pattern characteristic of pancreatic function. New
      pancreatic transcripts corresponding to novel tags were identified. SAGE should
      provide a broadly applicable means for the quantitative cataloging and comparison
      of expressed genes in a variety of normal, developmental, and disease states.

PMID- 7570005
TI  - AIDS intervention in Uganda.

PMID- 7570006
TI  - Max Planck Institutes brace for change.

PMID- 7570008
TI  - Center for the mind pleases the senses.

PMID- 7570007
TI  - Hubert Markl: animal behaviorist puts his learning to work.

PMID- 7570010
TI  - New studies trace the impact of tobacco advertising.

PMID- 7570011
TI  - Rajewsky to head EMBL's Italian lab.

PMID- 7570014
TI  - New clue to brain wiring mystery.

PMID- 7570009
TI  - Researchers protest attack on tobacco study.

PMID- 7570015
TI  - Metal-carbon bonds in nature.

PMID- 7570013
TI  - Defining the first steps on the path toward cell specialization.

PMID- 7570012
TI  - Antisense has growing pains.

PMID- 7570016
TI  - Calcium sparks in vascular smooth muscle: relaxation regulators.

PMID- 7570017
TI  - Neurotrophins and neuronal plasticity.
AB  - There is increasing evidence that neurotrophins (NTs) are involved in processes
      of neuronal plasticity besides their well-established actions in regulating the
      survival, differentiation, and maintenance of functions of specific populations
      of neurons. Nerve growth factor, brain-derived neurotrophic factor, NT-4/5, and
      corresponding antibodies dramatically modify the development of the visual
      cortex. Although the neuronal elements involved have not yet been identified,
      complementary studies of other systems have demonstrated that NT synthesis is
      rapidly regulated by neuronal activity and that NTs are released in an activity
      dependent manner from neuronal dendrites. These data, together with the
      observation that NTs enhance transmitter release from neurons that express the
      corresponding signal-transducing Trk receptors, suggest a role for NTs as
      selective retrograde messengers that regulate synaptic efficacy.

PMID- 7570018
TI  - Nanoscale complexity of phospholipid monolayers investigated by near-field
      scanning optical microscopy.
AB  - Near-field scanning optical microscopy of phospholipid monolayers doped with
      fluorescent lipid analogs reveals previously undescribed features in various
      phases, including a concentration gradient at the liquid-expanded/liquid
      condensed domain boundary and weblike structures in the solid-condensed phase.
      Presumably, the web structures are grain boundaries between crystalline solid
      lipid. These structures are strongly modulated by the addition of low
      concentrations of cholesterol and ganglioside GM1 in the monolayer.

PMID- 7570019
TI  - A methylnickel intermediate in a bimetallic mechanism of acetyl-coenzyme A
      synthesis by anaerobic bacteria.
AB  - Resonance Raman (RR) spectroscopy was used to identify a methylnickel adduct
      (upsilon Ni-C = 422 wave numbers) of carbon monoxide dehydrogenase (CODH) from
      Clostridium thermoaceticum. Formed at a nickel/iron-sulfur cluster on CODH called
      center A, the methylnickel species is the precursor of the methyl group of acetyl
      coenzyme A in an anaerobic pathway of carbon monoxide or carbon dioxide fixation.
      Rapid kinetic and RR studies demonstrated that methylation of nickel occurs by
      heterolysis of the methyl-cobalt bond (upsilon Co-C = 429 wave numbers) of a
      methylated corrinoid/iron-sulfur protein. In combination with the earlier finding
      of an iron-carbonyl adduct at center A, detection of the methylnickel
      intermediate establishes a bimetallic mechanism for acetyl-coenzyme A synthesis.

PMID- 7570020
TI  - T cell awareness of paternal alloantigens during pregnancy.
AB  - During pregnancy a semiallogeneic fetus survives despite the presence of maternal
      T cells specific for paternally inherited histocompatibility antigens. A mouse
      transgenic for a T cell receptor recognizing the major histocompatibility (MHC)
      antigen H-2Kb was used to follow the fate of T cells reactive to paternal
      alloantigens. In contrast to syngeneic and third-party allogeneic pregnancies,
      mice bearing a Kb-positive conceptus had reduced numbers of Kb-reactive T cells
      and accepted Kb-positive tumor grafts. T cell phenotype and responsiveness were
      restored after delivery. Thus, during pregnancy maternal T cells acquire a
      transient state of tolerance specific for paternal alloantigens.

PMID- 7570021
TI  - Relaxation of arterial smooth muscle by calcium sparks.
AB  - Local increases in intracellular calcium ion concentration ([Ca2+]i) resulting
      from activation of the ryanodine-sensitive calcium-release channel in the
      sarcoplasmic reticulum (SR) of smooth muscle cause arterial dilation. Ryanodine
      sensitive, spontaneous local increases in [Ca2+]i (Ca2+ sparks) from the SR were
      observed just under the surface membrane of single smooth muscle cells from
      myogenic cerebral arteries. Ryanodine and thapsigargin inhibited Ca2+ sparks and
      Ca(2+)-dependent potassium (KCa) currents, suggesting that Ca2+ sparks activate
      KCa channels. Furthermore, KCa channels activated by Ca2+ sparks appeared to
      hyperpolarize and dilate pressurized myogenic arteries because ryanodine and
      thapsigargin depolarized and constricted these arteries to an extent similar to
      that produced by blockers of KCa channels. Ca2+ sparks indirectly cause
      vasodilation through activation of KCa channels, but have little direct effect on
      spatially averaged [Ca2+]i, which regulates contraction.

PMID- 7570022
TI  - Localization of protein implicated in establishment of cell type to sites of
      asymmetric division.
AB  - Asymmetric division in Bacillus subtilis generates progeny cells with dissimilar
      fates. SpoIIE, a membrane protein required for the establishment of cell type,
      was shown to localize near sites of potential polar division. SpoIIE initially
      localizes in a bipolar pattern, coalescing at marks in the cell envelope at which
      asymmetric division can take place. Then, during division, SpoIIE becomes
      restricted to the polar septum and is lost from the distal pole. Thus, when
      division is complete, SpoIIE sits at the boundary between the progeny from which
      it dictates cell fate by the activation of a cell-specific transcription factor.

PMID- 7570023
TI  - Activation of cell-specific transcription by a serine phosphatase at the site of
      asymmetric division.
AB  - Cell fate is determined by cell-specific activation of transcription factor sigma
      F after asymmetric division during sporulation by Bacillus subtilis. The activity
      of sigma F is governed by SpoIIAA, SpoIIAB, and SpoIIE, a membrane protein
      localized at the polar septum. SpoIIAB binds to and inhibits sigma F, and SpoIIAA
      inhibits SpoIIAB, which prevents SpoIIAB from binding to sigma F. SpoIIAB is also
      a serine kinase that inactivates SpoIIAA. Here, it is demonstrated that SpoIIE
      dephosphorylates SpoIIAA-P and overcomes SpoIIAB-mediated inhibition of sigma F.
      The finding that SpoIIE is a serine phosphatase links asymmetric division to the
      pathway governing cell-specific gene transcription.

PMID- 7570025
TI  - South Dakota Health 2000: putting prevention into practice. Protecting our
      employees: the role of the professional nurse: Part 2.

PMID- 7570026
TI  - Thoughts on school nursing.

PMID- 7570024
TI  - Central command neurons of the sympathetic nervous system: basis of the fight-or
      flight response.
AB  - During stress, the activity of the sympathetic nervous system is changed in a
      global fashion, leading to an increase in cardiovascular function and a release
      of adrenal catecholamines. This response is thought to be regulated by a common
      set of brain neurons that provide a dual input to the sympathetic preganglionic
      neurons regulating cardiac and adrenal medullary functions. By using a double
      virus transneuronal labeling technique, the existence of such a set of central
      autonomic neurons in the hypothalamus and brainstem was demonstrated. These
      neurons innervate both of the sympathetic outflow systems and likely function in
      circumstances where parallel sympathetic processing occurs, such as in the fight
      or-flight response.

PMID- 7570027
TI  - Two recent Native American women's health education resource center projects
      address domestic violence in the Yankton Sioux Community.

PMID- 7570028
TI  - The South Dakota Cancer Pain Initiative ... a grassroots organization.

PMID- 7570029
TI  - Every person deserves a nurse.

PMID- 7570030
TI  - Profile of volunteer lobbyists.

PMID- 7570031
TI  - Report of SDNA/NEDDS survey: SD registered nurses with graduate degrees: a
      profile.

PMID- 7570032
TI  - [Morphometry of the sub-acromial space and its clinical relevance].
AB  - Rupture of the rotator cuff is one of the commonest (30%) pathologic findings in
      elderly dissecting room subjects. Together with the degenerative tendopathy
      associated with increasing age, this is due to mechanical damage to the distal
      parts of the tendons or the soft tissues lying in the subacromial space between
      the acromion, coracoacromial ligament, coracoid process and humeral head. The
      object of this investigation was to examine the influence of the decisive
      metrical parameters of the subacromial space in the macerated scapula. For this
      purpose, defined distances and angles of 343 macerated human scapulae were
      measured by means of an image analysing system, and the results evaluated
      statistically. It was found that the size of the subacromial space depends, not
      only upon variations in the form of the acromion itself, but also upon the
      acromial and scapula-spine angles. Marked projection of the coracoid process,
      which is dependent upon both the angle between the long axis of the scapula and
      the root of the coracoid process and the coracoid angle, plays an important part
      in the development of the so-called subcoracoid impingement syndrome: a
      constriction of the subscapularis tendon between the coracoid process and the
      head of the humerus. A clinical assessment of the absolute size of the
      subacromial space should take into account the size of the body; but sex, age,
      and the side involved are of little significance.

PMID- 7570033
TI  - [The anterolateral deltoid muscle flap-plasty: the procedure of choice in large
      rotator cuff defects].
AB  - We analysed the results of shoulder reconstruction using an anterolateral deltoid
      muscle flap plasty in 101 patients with large rotator cuff lesions. This method
      was first described in Apoil and Augereau in 1985. We modified and extended their
      technique. Regular follow-up examinations were possible in 100 patients (27
      females, 73 males, age 61.3 +/- 8.7 years). One patient died of sepsis of unknown
      aetiology during the hospital stay. All patients suffered from severe pain and
      sleepless nights prior to the operation. They also had long histories of
      unsuccessful and frustrating treatment. The rotator cuff lesions found
      intraoperatively were at least 5 x 5 cm in size. We used an anterolateral deltoid
      muscle flap to reconstruct these large defects. Physical therapy was started on
      the 1 postoperative day and was continued for about 6 months (6.8 +/- 2.6
      months). The average hospital stay was 10.9 +/- 5.3 days. After the treatment 90%
      of all patients were subjectively satisfied or very satisfied with the result,
      while 12% had moderate and 5% unsatisfactory results. No pain was felt at all by
      75% of the patients, and 21% showed decidedly less pain. Severe pain attacks were
      found in only 4% of the patients, but their pain was less intense than
      preoperatively. The shoulder function improved significantly, and 72% recovered
      their strength completely. Most of the patients were able to work after 6 months.
      The overall result was good to very good in 83%. This high percentage of good
      shoulder function and patient satisfaction makes this the operation technique of
      choice for large rotator cuff lesions.

PMID- 7570034
TI  - [Late results of surgical treatment of Tossy III acromioclavicular joint
      separation with the Balser plate].
AB  - Various surgical procedures have been recommended for the treatment of complete
      acromioclavicular joint separations. The results have been similar in case
      reports by various authors. From 1984 to 1992, 35 patients were operated on for
      acromioclavicular joint separations (Tossy III) in the Department of Surgery,
      Marien-Hospital, Dusseldorf, using Balser's hook plate. The postoperative
      morbidity rate was 14.3%. Follow-up examinations were performed on 30 patients
      (85.7%) with average follow-up of 4.1 years, using a rating system that include
      subjective, objective, and roentgenographic criteria. Fifty percent of patients
      had no complaints, but residual dislocation was found in 36.7% of cases. While 26
      patients (86.7%) were satisfied with the results of the operation, 30%
      demonstrated a fair result according to the scoring system. The complaints and
      clinical findings showed no correlation with the X-ray results, e.g.
      calcification or arthrosis, redislocations.

PMID- 7570036
TI  - [Results of surgery in acute subdural hematoma].
AB  - In a retrospective study the prognosis of acute subdural hematoma was considered
      with reference to the data of 255 patients who underwent surgery because of acute
      subdural hematoma during a period of 10 years in the Department of Neurosurgery
      of the Landesnervenklinik in Salzburg. The mortality rate was 43.5%, and 21.6%
      had a full functional recovery. The findings of the study confirm that the
      preoperative neurological condition, the age, the kind of accident sustained and
      the extent of concomitant brain injury influence on the prognosis decisively.

PMID- 7570035
TI  - [Swelling of the sternoclavicular joint].
AB  - From 1990 through 1993 nine patients presented with unexplained swelling of the
      sternoclavicular joint. In some cases a tumor was suspected. The clinical
      histories included trauma with injury of forearm and wrist or strain on the
      shoulder girdle without acute onset of any symptoms in the sternoclavicular
      joint. In trauma cases the time from injury to onset of symptoms was between 1
      day and 1 year (median 5 weeks). CT studies demonstrated widening of the joint
      space in two cases, thickening of the pectoral muscle in six cases and thickening
      of capsule and ligaments in five cases. In one case arthroplasty of the
      sternoclavicular joint was performed and in a second we performed a biopsy. The
      remaining cases were not treated. Other differential diagnoses to be considered
      in the case of a swelling of the sternoclavicular joint are listed.

PMID- 7570037
TI  - [Effect of primary fracture management on craniocerebral trauma in polytrauma. An
      animal experiment study].
AB  - Severe head trauma (BI) associated with long bone fractures is present in about
      60% of polytraumatized patients admitted to hospital. However, there is no
      consensus regarding early fracture stabilization in such patients. In an
      experimental sheep study, the influence of intramedullary nailing of the femur
      (IMNF) on a cold-induced, vasogenic brain edema (method of Klatzo) in combination
      with traumatic hemorrhagic shock (THS) was investigated. Three animal groups (n =
      6) were explored: group A, only BI; group B, BI and THS; group C, BI, THS and
      IMNF. The animals remained intubated, on controlled ventilation, sedated and
      received analgesia during the whole experiment. For a period of 6 h after the
      cold-induced brain injury the hemodynamic changes were measured and the
      intracranial pressure (ICP) was recorded in the left and the right hemisphere
      continuously. The hemorrhagic shock (MAP = 60 mm Hg) was maintained over 1.5 h.
      At the end of the reperfusion period (2 h) the nailing of the femur was
      performed. The animals were killed and the percentage water content of the brain
      was determined and compared with the brain water content of a control group (n =
      6). There were no significant differences in ICP between groups A, B and C before
      or after IMNF, but in group C the ICP increased significantly after nailing.
      Brain water content in group C was significantly higher than in the control group
      and slightly significantly higher than in groups A and B. Brain edema and ICP are
      increased by IMNF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570038
TI  - [Does initial management of polytrauma patients have an effect on the development
      of multiple organ failure? Evaluation of preclinical and clinical data of 1,112
      polytrauma patients].
AB  - The aim of this study was to investigate criteria in the preclinical and early
      clinical treatment which contribute to the development of posttraumatic multiple
      organ failure (MOV). In a retrospective study, 1112 primarily treated patients
      with multiple trauma and an injury severity > 20 on the Hanover Polytrauma Score
      (PTS) were investigated. The patients were classified according to Goris into
      groups with MOV (+MOV; 16.8%) and without MOV (-MOV). Patients with MOV had a
      significantly higher injury severity score (39.1 vs 33.7). A significantly higher
      proportion of +MOV patients had severe trunk injuries: thorax (85.2% vs 68.9%),
      abdomen (37.0% vs 26.1%) and pelvis (49.4% vs 35.6%). -MOV patients had
      significantly more injuries of the extremities (83.6% vs 72.8%). Differences in
      preclinical management were seen. The proportion of helicopter transports was
      significantly higher in the -MOV group (67.9% vs 57.8%). A positive effect was
      seen for early preclinical intubation. Patients who were intubated before arrival
      at the hospital had the same rate of MOV incidence as late intubated patients,
      but they had significantly higher (trunk) injury severity. +MOV patients received
      a significantly higher quantity of fluid replacement. In particular, more blood
      units and fresh frozen plasma were given in the first 24 h after trauma, possibly
      in association with the trunk injuries and the consequently increased hemorrhage.
      The mortality for all patients was 27.2%, in the +MOV group 60.4%. Posttraumatic
      MOV was the most frequent cause of death (37.5%), and the mean time of death
      after MOV was 16.7 days.

PMID- 7570039
TI  - [Acute venous stasis in the area of the head after bungee-jumping. A report of 2
      cases].
AB  - Jumping from bridges or cranes while secured by an elastic rope is called bungee
      jumping, and it is an increasingly popular sport. We report on two bungee jumpers
      who suffered from symptoms of acute venous stasis in the head. These included
      skin edema, purpura-like bleeding in the face and the conjunctiva, dizziness,
      confusion and, in one case, transient visual problems. With increasing diameter
      and decreasing elasticity of the rope the deceleration with the head foremost
      leads to temporary engorgement of blood vessels entailed by capillary leaking.
      Nearly a century ago, Perthes reported similar symptoms of acute venous stasis in
      the head as a result of thoracic compression.

PMID- 7570040
TI  - [Pediatric femoral shaft fracture: effect of treatment procedure on results with
      reference to somatic and psychological aspects].
AB  - When treating femoral shaft fractures in children both somatic (axial/rotational
      misalignment) and psychological sequelae of the treatment have to be taken into
      consideration. We performed a retrospective study on the somatic and
      psychological outcome in 38 children under the age of 10 years with femoral
      fractures from 1989 to 1991. Twenty-four were treated conservatively (i.e. by
      traction), while 14 had surgery. Average time in hospital was significantly
      shorter in the operative group (9 days) than in the conservative group (37 days).
      The rate of rotational misalignment > 10 degrees was 14% after operation and 45%
      after traction. Psychological evaluation revealed a positive influence on
      intellectual development in 21% of conservatively treated children but there were
      disturbances in motor development (37%), family environment (17%) and general
      health (25%) in this group. Operative treatment was superior in causing no
      adverse effects in these fields. We therefore recommend surgery for femoral
      fractures in children older than 3 years.

PMID- 7570041
TI  - Advances in the management of patients with thyroid disease.
AB  - Discoveries related to thyroid immunology, especially concerning the thyroid
      stimulating hormone (TSH) receptor, may facilitate new immunologic approaches to
      the therapy of Graves' disease and the thyroiditis syndromes. Advances in
      genetics are being applied to the thyroid hormone resistance syndromes and
      papillary and medullary carcinomas. The development of ever more sensitive TSH
      assays has led to the detection of subclinical thyroid disease, which has special
      implications for the sick and elderly patients. Sensitive TSH assays also allow
      more precise titration of levothyroxine (T4) dosages, especially for patients
      with a past history of thyroid cancer. Evidence continues to accumulate
      suggesting that postmenopausal women on T4 doses that suppress the TSH level
      below 0.1 ulU/mL have lower bone mineral density than matched patients with
      healthy TSH levels. Also, pregnant hypothyroid women need higher T4 doses to
      normalize the TSH levels. In the evaluation of thyroid nodules, fine-needle
      aspiration biopsy is the single most definitive modality in selecting the
      patients for surgery. Scintigraphy provides a complimentary role, especially in
      defining autonomously functioning thyroid adenomas (AFTA), because these should
      not be treated with T4 suppression. Ultrasound-guided needle biopsy is
      occasionally helpful with nodules that are difficult to palpate. Concern for
      possible tracheal compression after treatment of toxic multinodular goiter with
      large doses of radioactive iodine (I-131) in the range of 50 to 150 mCi (1.85 to
      5.5 GBq) does not seem warranted. Work, primarily out of Italy, suggests AFTA can
      be ablated with repeat ethanol injections. Residual tissues after thyroidectomy
      for differentiated carcinoma can be "stunned" by tracer doses of 131I greater
      than 3.0 mCi (111 MBq), which diminishes the uptake and effectiveness of a
      subsequent therapy dose. Positron emission tomograph, imaging with thallium-201,
      and Technetium 99m Sestamibi can identify a small number of patients shown to
      have metastases from differentiated thyroid carcinoma by increasing thyroglobulin
      levels in the absence of 131I uptake. Several groups have recently advocated
      treating such patients empirically with 131I.

PMID- 7570043
TI  - Adrenal cortical and medullary imaging.
AB  - Adrenal disease can be manifested by endocrine dysfunction or anatomic
      abnormalities detected by cross-sectional imaging modalities. With the advent of
      newer and more reliable in vitro assays and a better understanding of the
      spectrum of adrenal pathology, the physician can now adopt a more accurate and
      cost-effective approach to the diagnosis of adrenal disease. Both functional and
      anatomic imaging modalities can play an important role in the evaluation of the
      incidental adrenal mass, the early detection of adrenal metastases,
      differentiation of the various causes of Cushings's syndrome, selection of
      patients for potentially curative surgery in primary aldosteronism and adrenal
      hyperandrogenism, and localization of pheochromocytomas and neuroblastomas. The
      usefulness of the adrenal cortical radiopharmaceutical, 131I-6-beta
      iodomethylnorcholesterol (NP-59), and the adrenal medullary radiopharmaceuticals,
      131I and 123I-metaiodobenzylguanidine (MIBG), is detailed for these various
      clinical settings and the role of NP-59 and MIBG is contrasted to that of the
      cross-sectional modalities, computed tomography and magnetic resonance imaging
      (MRI). Incidental adrenal masses are common, but malignancies are few. Imaging
      studies select those patients who require a further evaluation by biopsy
      examination or adrenalectomy. In the hyperfunctioning endocrine states, such as
      Cushing's syndrome, primary aldosteronism, adrenal androgenism, and
      pheochromocytoma, correlation of biochemical findings with both functional and
      anatomic imaging is necessary to avoid inappropriate and ineffective surgical
      intervention, yet not miss an opportunity for curative resection. Lastly, MIBG
      and MRI are complementary in the detection and staging of neuroblastoma.

PMID- 7570042
TI  - Sestamibi parathyroid imaging.
AB  - Since the introduction of technetium-99m (99mTc) sestamibi (hexakis-2
      methoxyisobutyl isonitrile) as a parathyroid imaging agent in 1989, many
      investigators using several different imaging protocols have reported uniformly
      excellent results for localization of parathyroid adenomas. Exact localization of
      hyperplastic parathyroid glands has not met with as much success. However, the
      results of multiple comparative studies suggest that the diagnostic utility of
      sestamibi protocols equals or exceeds other noninvasive, nonscintigraphic imaging
      strategies, including high-resolution ultrasound, computed tomography, and
      magnetic resonance imaging. Two different, but not necessarily mutually exclusive
      imaging strategies have been used: subtraction imaging using iodine-123 (123I) or
      99mTc sodium pertechnetate as the thyroid agent, and sestamibi dual-phase
      imaging, which takes advantage of differential washout of sestamibi from thyroid
      and parathyroid tissue. Sestamibi subtraction imaging has been shown to have
      greater sensitivity for abnormal parathyroid glands compared with thallium-201
      subtraction imaging using pooled data, 87% versus 71%, respectively. Dual-phase
      sestamibi imaging protocols are much more variable in their conduct and have a
      much greater variability in sensitivity, 43% to 91%, but with a pooled
      sensitivity of 73%. Data suggest that dual phase techniques are at least as
      sensitive, and in optimized protocols, superior to, thallium-201 subtraction
      techniques. This superiority is attributed to the favorable washout kinetics of
      sestamibi and the superior imaging characteristics of the 99mTc label.
      Specificity and positive predictive value for both sestamibi techniques are very
      high, typically greater than 90% and at least equal to thallium-subtraction
      protocols, although specificity may be slightly lower for sestamibi subtraction
      techniques. Therefore, sestamibi protocols are the scintigraphic procedure of
      choice for parathyroid imaging. Dual-phase sestamibi protocols are more robust
      and lend themselves to single photon emission computer tomography (SPECT)
      imaging, and may be followed sequentially by subtraction techniques if results
      are inconclusive. Despite the excellent results of sestamibi parathyroid imaging,
      it is unclear whether this accuracy can compete with the even better success of
      an experienced surgeon in initial surgeries for hyperparathyroidism, and routine
      preoperative imaging before initial surgery is still controversial. However,
      sestamibi parathyroid imaging is an excellent addition to a correlative imaging
      approach in reoperations for persistent and recurrent hyperparathyroidism.

PMID- 7570045
TI  - Somatostatin-receptor imaging in lymphoma.
AB  - Patients with Hodgkin's or non-Hodgkin's lymphoma are staged for treatment based
      on the extent of known disease involvement and the histopathologic grading of the
      disease. Radiological techniques, including computed tomography, usually depend
      on estimates of lymph node enlargement and mass effects as the criterion for
      disease involvement. Lymphomatous tissue obtained at surgery has shown high
      density somatostatin receptors. Several groups have evaluated the utility of
      111In-DTPA-pentetreotide (Octreoscan, Mallinckrodt, St. Louis, MO) to detect
      lymphomatous tissue for more accurate staging of patients with lymphoma. The
      procedure is safe; both Hodgkin's and non-Hodgkins disease involvement is
      identified. The results, however, have not been uniformly predictive of disease
      involvement. Consequently, the routine use of this technique in place of
      currently used anatomic imaging methods is not recommended at this time. The
      significance of detecting somatostatin receptors in vivo in patients with
      malignant lymphoma requires further study.

PMID- 7570046
TI  - Therapy of neuroendocrine tumors with radiolabeled MIBG and somatostatin
      analogues.
AB  - The increased understanding of the neuroendocrine tumors at a cellular and
      molecular level has led to the development of new radiopharmaceuticals for
      imaging. Two of the imaging agents include 131I metaiodobenzylguanidine (131I
      MIBG) and 111In-DTPA-D-Phe1-octreotide (111In-pentetreotide) each having specific
      localization in certain neuroendocrine tumors. The selective uptake of these
      radiopharmaceuticals by the tumor cells has generated interest in potential use
      for targeted radiotherapy for neuroendocrine tumors. 131I-MIBG has been used to
      treat patients with pheochromocytoma, neuroblastoma, carcinoid tumors, medullary
      thyroid carcinoma, and paragangliomas. The tumor responses have been variable
      with the most encouraging results being in patients with pheochromocytoma. The
      dose-limiting toxicity has been thrombocytopenia or granulocytopenia. 111In
      pentetreotide has been used as therapy in only a few patients and has resulted in
      objective evidence of tumor responses. A therapeutic agent using a somatostatin
      analogue will most likely require radiolabeling with a beta- or possibly an alpha
      emitting radionuclide to achieve significant and durable tumor responses.

PMID- 7570047
TI  - False-positive results of I-131 whole-body scans in patients with thyroid cancer.

PMID- 7570044
TI  - Somatostatin receptor imaging of neuroendocrine tumors with indium-111
      pentetreotide (Octreoscan).
AB  - Somatostatin, a naturally occurring 14-amino acid peptide, can be thought of as
      an anti-growth hormone and functional down-regulator of sensitive tissue. Most
      neuroendocrine tumors seem to possess somatostatin receptors in sufficient
      abundance to allow successful scintigraphic imaging with radiolabeled
      somatostatin congeners. Several of these, including Indium-III-DTPA Pentetreotide
      (Octreoscan [Mallinckrodt Medical, St. Louis, MO]), which was approved for
      clinical use by the Food and Drug Administration in June 1994, have been of
      considerable value in scintigraphically identifying various neuroendocrine
      tumors. The Octreoscan compares favorably with other imaging modalities. The
      success of somatostatin receptor imaging in evaluating patients with suspected
      neuroendocrine tumors, including identifying otherwise radiographically occult
      lesions, has resulted in ranking somatostatin receptor imaging as the prime
      imaging procedure in patients with suspected neuroendocrine tumors at The Ohio
      State University.

PMID- 7570048
TI  - Increased uptake around the hip joint.

PMID- 7570049
TI  - Overview: oral granisetron (Kytril tablets) prophylaxis for chemotherapy-induced
      nausea and vomiting.

PMID- 7570050
TI  - Prophylaxis with oral granisetron for acute emesis induced by moderately
      emetogenic chemotherapy.

PMID- 7570051
TI  - Single-agent oral granisetron for the prevention of acute cisplatin-induced
      emesis: a double-blind, randomized comparison with granisetron plus dexamethasone
      and high-dose metoclopramide plus dexamethasone.

PMID- 7570052
TI  - A pharmacologic profile of oral granisetron (Kytril tablets).

PMID- 7570053
TI  - Preventing chemotherapy-induced nausea and vomiting: an update and a review of
      emesis.

PMID- 7570054
TI  - Inflammatory breast cancer: what is the appropriate therapy for patients who have
      a clinical response to induction chemotherapy?

PMID- 7570055
TI  - Colorectal cancer biology: clinical implications.

PMID- 7570056
TI  - Screening for colon cancer: a review of current and future strategies.

PMID- 7570057
TI  - New imaging techniques in colorectal cancer.
AB  - The ability to visualize biochemical processes in tumor tissues by PET and
      correlate these findings with anatomic imaging such as CT and MRI gives new
      insight into the metabolic and physiologic aspects of the tumor tissue. This may
      permit discrimination between recurrent colorectal carcinoma and some benign
      lesions. The potential for its use in pharmacology or in monitoring drug therapy
      is just beginning to be explored. Improvements in acquisition techniques such as
      whole body imaging, and in methods of absolute quantitation will be important for
      standardizing image information and making it more widely applicable. Careful
      evaluation of the impact on patient outcome and clinical decision making are
      vital in determining the further use of this technology and the planned
      multicenter trial evaluating cost-effectiveness is welcome step in this
      direction.

PMID- 7570058
TI  - Adjuvant chemotherapy for colon and rectal cancer.

PMID- 7570059
TI  - Postoperative evaluation of patients with colorectal cancer.

PMID- 7570060
TI  - Colorectal cancer: hepatic-directed therapy--the role of surgery, regional
      chemotherapy, and novel modalities.

PMID- 7570062
TI  - Growth factor requirements for normal and leukemic cells.
AB  - Both normal bone marrow and leukemic progenitor cells require growth factors for
      their survival and proliferation. A variety of factors that affect the growth of
      these cells have been identified, but the complete repertoire of factors that are
      of relevance in vivo have yet to be established. These growth factors interact
      with specific cell surface proteins that then alter the internal milieu of the
      cell resulting in changes in proliferation and differentiation. Through an
      understanding of the receptor ligand interactions and the signal transduction
      pathways that are activated, it may be possible to design therapeutic strategies
      that interfere with the growth promoting signals in leukemic cells.

PMID- 7570061
TI  - Metastatic colorectal cancer: advances in biochemical modulation and new drug
      development.

PMID- 7570064
TI  - The molecular biology of myeloproliferative disorders as revealed by chromosomal
      abnormalities.

PMID- 7570065
TI  - Cytokines and their antagonists in myeloid disorders.

PMID- 7570063
TI  - Expansion of myeloid stem cells in culture.

PMID- 7570066
TI  - Pseudoreticulocytosis in a case of myelodysplastic syndrome with translocation
      t(1;14) (q42;q32).

PMID- 7570067
TI  - Update: lymphoid neoplasms--molecular characterizations of non-Hodgkin's
      lymphomas: impact on patient management.

PMID- 7570068
TI  - The interrelationships of body fat, exercise, and hormonal status and their
      impact on reproduction and bone health.

PMID- 7570069
TI  - Weight gain, nutrition, and pregnancy outcome: findings from the Camden study of
      teenage and minority gravidas.

PMID- 7570070
TI  - Nutrition support of maternal phenylketonuria.

PMID- 7570071
TI  - The influence of race and previous pregnancy outcome on outcomes in the current
      pregnancy.

PMID- 7570072
TI  - Individual nutrient effects on length of gestation and pregnancy outcome.

PMID- 7570073
TI  - Nutritional risk factors among low-income pregnant US women: the Centers for
      Disease Control and Prevention (CDC) Pregnancy Nutrition Surveillance System,
      1979 through 1993.

PMID- 7570074
TI  - The influence of fetal and maternal factors on the distribution of birthweight.
AB  - This review of common risk factors for low birthweight emphasizes the usefulness
      of examining the entire distribution of birthweight. Of the factors we examined,
      only short gestational age seemed to affect the low end of the birthweight
      distribution in the form of skewness. Most factors, such as maternal race, infant
      sex, plurality, altitude, education, and smoking seem to affect the entire
      birthweight distribution, indicating a generalized effect. With the exceptions of
      race, infant sex, parity, and altitude, these factors seemed to have similar
      associations with both low birthweight and infant mortality. However, only the
      effects of race and sex on mortality have been repeatedly studied in detail for
      different combinations of gestational age and birthweight. A few of the factors
      examined, notably infant sex and parity, have opposite associations with
      birthweight and infant mortality. Female infants and firstborn infants have lower
      birthweights than their counterparts, but are more likely to survive. For factors
      that significantly affect the birthweight distribution, but do not affect
      mortality equally across the birthweight distribution, the development and use of
      population-based standards may result in less misclassification of IUGR. Separate
      standards by infant sex, altitude, and perhaps race may lead to more accurate
      classification of intrauterine growth. Last, the majority of risk factors have
      differential effects on birthweight depending on the level of the associated
      factors. For example, low maternal age and low prepregnancy BMI are associated
      with both increased risk of low birthweight and poor infant survival. Older
      maternal age and high prepregnancy BMI are associated with reduced risk of low
      birthweight, but with increased risk of infant mortality. One possible
      explanation is that young maternal age and low prepregnancy BMI are associated
      with adverse behavioral risk factors such as cigarette smoking, whereas increased
      age and high prepregnancy BMI are associated with gestational diabetes,
      multiparity, and genetic defects. It is possible that the greater variation in
      birthweight at the high end of the scale is indicative of increased risk of
      mortality. Thus, higher birthweight does not always equal better birth outcomes.

PMID- 7570075
TI  - The DeGuiche syndrome.

PMID- 7570076
TI  - Case of the season. Pulmonary blastoma.

PMID- 7570077
TI  - Magnetic resonance imaging of the shoulder: review.

PMID- 7570078
TI  - Magnetic resonance imaging of the elbow.

PMID- 7570079
TI  - The wrist.

PMID- 7570080
TI  - The knee.

PMID- 7570081
TI  - Magnetic resonance imaging of the ankle and foot.

PMID- 7570082
TI  - [Caring, defending the autonomy of the patient].

PMID- 7570083
TI  - [Boutros Boutros-Ghali at the United Nations. Message for the International Day
      of the Family].

PMID- 7570084
TI  - [The hands of the nurse in caring].

PMID- 7570085
TI  - [Noise in society].

PMID- 7570087
TI  - [The patient with alcoholic intoxication in the emergency service].

PMID- 7570086
TI  - [Caring for families of different cultures. Skill at meeting].

PMID- 7570088
TI  - [The nightly cramps of the elderly].

PMID- 7570089
TI  - [Organ transplantation according to the legislation for the National Donor
      Registration].

PMID- 7570091
TI  - [Ultraviolet radiation].

PMID- 7570090
TI  - [Treating chronically ill adolescents].

PMID- 7570092
TI  - [Prevention of the adverse effects of immobility].

PMID- 7570094
TI  - [Palliative care for terminal patients].

PMID- 7570095
TI  - [Effect of chemical pollution on the elderly].

PMID- 7570096
TI  - [Mutual message for health promotion].

PMID- 7570093
TI  - [Long-term estrogen substitute therapy].

PMID- 7570097
TI  - [A vision of emergency care units of tomorrow].

PMID- 7570099
TI  - [School and hospital in the resolution of a problem].

PMID- 7570098
TI  - [The future of cataract operations. Long-term implants to be expected].

PMID- 7570100
TI  - [Caring ...].

PMID- 7570101
TI  - [Try for integration, not for fragmentation].

PMID- 7570102
TI  - [Nursing according to the perspectives of Roper, Logan and Tierney. 2 case
      studies].

PMID- 7570103
TI  - [Perception of different religious creeds in relation to birth, disease and
      death].

PMID- 7570104
TI  - [An observation on the pacemaker current I(f) in sheep cardiac Purkinje fibers
      under ischemia-mimic condition].
AB  - Effects of "ischemia" and adrenergic agonists on pacemaker current I(f) were
      observed in sheep cardiac Purkinje fibers. After perfusion with ischemia-mimic
      solution for 15, 30 and 60 min, the amplitude of I(f) current were decreased at
      all membrane potential levels between Ec-60 mV to -120 mV (n = 7, P < 0.05),
      activation time and half activation time to a steady state value of I(f) current
      were prolonged (n = 7, P < 0.05), activation curve of I(f) shifted to a more
      hyperpolarized position. Isoproterenol 1 x 10(-6) mol/L increased amplitude of
      I(f) current (n = 10, P < 0.05), shortened the activation time and half
      activation time (n = 10, P > 0.05), and shifted the activation curve to a more
      depolarized position; but isoproterenol of 1 x 10(-6) mol/L could not completely
      reverse the inhibitory effects of "ischemia" on I(f) current. In the presence of
      5 x 10(-7) mol/L propranolol the effects of phenylephrine 5 x 10(-5) mol/L on
      I(f) current was variable; but aggravated the inhibitory effects of I(f) current
      due to "ischemia". The above results indicate that normal pacemaker activity of
      ventricular Purkinje fibers does not increase but rather decrease during
      myocardial ischemia-mimic condition, an observation suggesting that acute
      ischemic ventricular arrhythmia may not be due to abnormal strengthening of
      normal ventricular pacemaker activity.

PMID- 7570105
TI  - [A study on hypotensive mechanism of adrenomedullin (13-52)].
AB  - In the present study the hypotensive mechanism of AdM (13-52) was investigated in
      rats, both in vitro and in vivo. It was found that the hypotensive effect of AdM
      (13-52) could be partially inhibited by L-NG-nitro-arginine (LNNA), an inhibitor
      of nitric oxide synthase. The vasodilator effect of AdM (13-52) was dependent on
      vascular endothelium and inhibited by LNNA in a dose-dependent manner. This LNNA
      induced inhibitory effect could be reversed with L-Arginine. In addition, the
      vasodilator effect of AdM (13-52) disappeared with methylene blue (MB), which
      blocked cGMP formation. Using radioimmunoassay it was shown that LNNA lowered,
      but AdM (13-52) elevated the vascular cGMP content, while vascular cGMP content
      was not altered by co-application of AdM (13-52) and LNNA. The above results
      suggest that the vasodilator effect of AdM (13-52) might be mediated by nitric
      oxide.

PMID- 7570106
TI  - [Effects of long-term hypoxia on intracellular pH and membrane potential of
      cultured rat carotid body glomus cells].
AB  - In the present study, the effects of long-term hypoxia on cultured glomus cells
      of rat carotid body were investigated. Spraque-Dawley (SD) rats (weighing about
      100 g) were kept in a decompression chamber for 7-10 days to simulate the
      environment at an altitude of 5,000 m above sea level at first. Then the carotid
      bodies were removed from the anesthetized animals and dissociated to obtain
      individuals or small clusters of glomus cells. These cells were cultured under
      hypoxic condition (11% O2, 5% CO2, 84% N2) for 2-3 days. Control samples from
      normal SD rats (normoxic rat) were cultured in normoxic (21% O2, 5% CO2, 74% N2)
      or hypoxic conditions. Intracellular pH (pHi) and membrane potential (MP) of
      glomus cells of both the groups were simultaneously measured with pH-sensitive
      and conventional microelectrodes. The results indicate that: (1) Long-term
      hypoxia decreased pHi and increased MP of the cultured glomus cells to a degree
      far greater than acute hypoxia did; (2) The mean pHi and MP of the glomus cells
      of the normoxic rat, but cultured under hypoxic environment, recovered
      approximately to control values when measured under normoxic condition, whereas
      those of the long-term hypoxic rat cells did not.

PMID- 7570107
TI  - [Protective effect of endothelium-derived relaxing factor on ischemic (hypoxic)
      and reperfused (reoxygenated) myocardium].
AB  - The present study is undertaken to investigate the effects of NO, its inhibitor L
      NNA and its procursor L-Arg on the status of myocardial tissue during ischemia
      (hypoxia) and reperfusion (reoxygenation) in two different models, i.e.
      Langendorff heart and cultured heart cells of rat. The results were as follows:
      (1) When heart perfusion was stopped for 30 min and reinstitued for 20 min with K
      H buffer containing NO, the coronary flow rate (CFR), left ventricular pressure
      (LVP) and +/- dp/dtmax increased significantly. When NO was replaced by L-NNA
      opposite effects were observed. L-Arg alone was without effect on CFR, LVP and +/
      dp/dtmax, but attenuated the decreasing effect of L-NNA on CFR. NO decreased MDA
      and NAGase content of myocardium while L-NNA increased them. (2) When cultured
      ventricular myocytes were subjected to hypoxia for 30 min and reoxygenated for 20
      min, none of the substances under investigation showed any effects on Ca2+
      content of heart cells, but all of them decreased MDA, NAGase content of the
      culture tissue after reoxygenation. The above findings show that NO plays an
      important role in protecting myocardium from ischemic and reperfused injury by
      improving blood supply of reperfused myocardium and attenuation of oxygen free
      radical injury.

PMID- 7570108
TI  - [Effect of insulin on the function of pancreatic exocrine].
AB  - Pancreatic function was determined in the diabetic rats prepared with STZ, a
      compound specifically damaging B-cells of the islets. The results indicated that
      in STZ rats the amylase content and the level of amylase mRNA in pancreas were
      significantly decreased. Studies in vitro showed that the binding of 125I-insulin
      with diabetic acini was much higher than that of control (P < 0.01). The uptake
      of the 3H-glucose, the incorporation of 3H-leucine in acini, and the Na(+)-K+
      ATPase activity in acinar membrane of diabetic rats were also significantly lower
      than that of the control rats (P < 0.01). However, the above-mentioned
      alternations could be reversed by replacement of insulin. These results indicate
      that insulin plays an important regulating role on the function of pancreatic
      acini.

PMID- 7570110
TI  - [Morphine blocked the exitatory amino acid mediated membrane current in ambigual
      motoneurons of the rat].
AB  - Excitatory postsynaptic potentials (EPSPs) and responses of neurons in the
      compact formation of the neucleus ambiguus (AMBc) to pressure-ejected or bath
      applied test substances were recorded intracellularly from sagittal slices of
      Sprague-Dawley rat medulla containing subnucleus centralis of solitary complex
      (NTSc), AMBc and solitarioambigual pathway. In 5 cells, recorded spontaneous
      EPSPs could be blocked by morphine (3-5 pmol) to AMBc. Electrical stimulation of
      NTSc evoked EPSPs in AMBc neurons, the amplitude of which were decreased to 71.1
      +/- 6.2% (P < 0.001) with the addition to morphine. The morphine effect could be
      abolished by bath-applied naloxone (50 nmol/L). The amplitude of membrane
      depolarization induced by pressure-ejected N-methyl-D-aspartate (NMDA, 0.5-1.0
      pmol), acetylcholine (3 pmol) and quisqualate (0.1-0.5 pmol) to NTSc could also
      be decreased by bath-applied morphine (10 mumol/L) respectively to 38.1 +/- 5.7%
      (P < 0.001), 32.8 +/- 5.5% (P < 0.01) and 29.6 +/- 7.1% (P < 0.05). The above
      results suggest that morphine is capable of block by NMDA, ACh and non-NMDA
      receptors, increaseing the M-current and decreasing the permeability of Na+ and
      Ca2+.

PMID- 7570109
TI  - [Participation of dopamine on the muscarinergic inhibitory effect of substance P
      on gastric myoelectric activity and motility].
AB  - Our previous study showed that microinjection of substance P (SP) into caudate
      nucleus inhibits gastric myoelectric fast wave and gastric motility, an effect
      mediated by muscarinic receptor. The present investigation showed that this
      effects of SP could be blocked by coinjected SP antiserum or SP antagonist [Arg6,
      D-Trip7,9, MePhe8]-SP6-11 or D2 dopamine antagonist haloperidol. In addition,
      microinjection of dopamine (DA) into caudate nucleus could also inhibit gastric
      fast wave and motility, an effect again being blockable by coinjected DA
      antagonist haloperidol or atropine. Thus, it appears that the muscarinergic
      inhibitory effect of SP on gastric fast wave and motility is mediated by D2
      dopamine receptor.

PMID- 7570112
TI  - [Inhibitory effect of interleukin-1 beta on insulin release from isolated rat
      pancreatic islets and the reversal action of testosterone].
AB  - Insulin release from pancreatic islet cells of neonatal rats could be markedly
      inhibited by a previous incubation of cells with interleukin-1 beta (5-20 U/ml)
      for 20 h even under high glucose (20 mmol/L) stimulation. This inhibitory effect
      of IL-1 beta on insulin release could be reversed by testosterone (10(-10)
      mol/L), which was accompanied by an increase of the insulin content in islet
      cells.

PMID- 7570113
TI  - [Inhibitory effects of calcium channel antagonist on the proliferation of
      vascular smooth muscle cells induced by adrenoceptor activators].
AB  - In cultured vascular smooth muscle cells (VSMC) of SD rat, it was demonstrated
      that 10(-6) - 10(-5) mol/L NE and 10(-7) - 10(-5) mol/L isoproterenol stimulated
      proliferation and 3H-TdR incorporation of the cells in a dose dependent manner.
      These effects might be significantly inhibited by co-incubation with either alpha
      receptor blocker phentolamine (10(-6) mol/L) or beta-receptor blocker propranolol
      (10(-5) mol/L). It was also found that cell counting and 3H-TdR incorporation
      were markedly decreased after incubation nifedipine (10(-6) mol/L) or verapamil
      (10(-6) mol/L) with NE (P < 0.01 as compared to that of NE group). It was further
      observed that nifedipine and verapamil inhibited DNA synthesis and proliferation
      of VSMC induced by isoproterenol.

PMID- 7570111
TI  - [Central mechanism of inhibitory effect of histamine H1-receptor agonists PEA on
      gastric acid secretion].
AB  - The present experiment is undertaken to study the central mechanism of the
      inhibitory effect of 2-pyridylethylamine (PEA, i.c.v.) on the gastric acid
      secretion. Gastric acid was continuously washed out with 37 degrees C saline by
      means of a perfusion pump in male adrenalectomized wistar rats. Drugs were
      injected into the third ventricle to examine the effect on pentagastrin-induced
      (160 micrograms/kg, s.c.) gastric acid secretion. The results were as follows:
      (1) Pretreatment with CRF-antiserum (2.5 microliters, 1:20,000, i.c.v.) blocked
      the inhibitory effect of PEA (10 micrograms, i.c.v.) on gastric acid secretion.
      (2) Administration of CRF (1 and 2 micrograms, i.c.v.) or beta-endorphin (0.94
      and 1.25 micrograms, i.c.v.) markedly inhibited the gastric acid secretion. (3)
      Pretreatment with naloxone (5 micrograms, i.c.v.) blocked the inhibitory effect
      of CRF (1 microgram, i.c.v.), but the inhibitory effect of beta-endorphin (0.94
      microgram, i.c.v.) was not changed by pretreatment with CRF-antiserum (1:20,000,
      2.5 microliters, i.c.v.). These results suggest that PEA stimulates the release
      of hypothalamic CRF which stimulates the release of hypothalamic endogenous
      opioid peptides. The peptides again induces vagus nerve-mediated inhibitory
      effect on gastric acid sceretion.

PMID- 7570114
TI  - [Effect of acetylcholine on the proliferation of T lymphocyte of rat spleen].
AB  - Experiments were performed to determine the effect of various concentrations of
      acetylcholine (ACh) (10(-10) to 10(-4) mol/L) on the proliferation of spleen
      cells of rat to concanavalin (Con A). ACh at 10(-9) mol/L to 10(-4) mol/L range
      significantly enhanced the proliferation of T cells, reaching a maximum at 10(-7)
      and 10(-6) mol/L. The proliferation of lymphocytes first stimulated by various
      concentrations of ACh (10(-9), 10(-7) or 10(-5) mol/L) for one hour and incubated
      with Con A for 72 h still showed increase. When ACh was washed off for one hour,
      the proliferative enhancement of lymphocytes to Con A remained to occur. However,
      ACh did not enhance the proliferation of T cells which were once stimulated with
      Con A for 6 h. Atropine at 10(-7) or 10(-6) mol/L abolished completely the effect
      of ACh at 10(-9) or 10(-5) mol/L. The action of ACh at 10(-7) mol/L could be
      blocked by 10(-6) mol/L atropine. These data suggest that ACh at a wide range of
      concentrations can enhance cellular immunity, an effect occurring either before
      or after T cells are activated through muscarinic cholinergic receptors.

PMID- 7570116
TI  - [Participation of septum on the increase of plasma cortisol level induced by
      stimulation of the greater splanchnic nerve of cats].
AB  - Experimens were performed on 36 cats, showing that stimulation of the central end
      of the left major splanchnic nerve induced an increase of the plasma cortisol
      level. The centripetal effect was abolished by lesioning the septal nuclei, just
      as the same as injection of propranolol into the nuclei; but phentolamine had no
      such preventive action. All the findings show that it is the noradrenergic beta
      receptor system of the septal nuclei that exerts a considerable effect on
      cortisol secretion.

PMID- 7570115
TI  - [Synaptic connections between the neurons and catecholaminegic fibres in the
      hippocampal transplant of rat].
AB  - The foetal hippocampal tissue (transplant) at 17th day of embryonic age was
      implanted into the ventral hippocampus of adult rats (host). The
      catecholaminergic fibre projections in the hippocampal transplants 90 days after
      operation were studied by immunohistochemical technique. It was observed that in
      the host hippocampus there was a large population of TH- immunoreactive slender
      fibres of only 0.5-1 microns in diameter. These fibres were distributed more
      densely in the hippocampal hilus and CA3 transparent layers than in molecular
      layers, but sparsely in pyramidal or granular layers. In the molecular and
      cellular layers of transplanted hippocampus some thicker (> 1 micron) TH-positive
      fibers were ended in a relatively dense branching. The immunoelectron-microscopic
      observations showed that many TH-positive boutons made synaptic contacts with
      immunonegative dendrites and dendritic spines in the hippocampal transplants, the
      majority of which were asymmetrical synapses with a 30 nm synaptic cleft and
      conspicuously thickened postsynaptic membranes. It is concluded that
      catecholaminergic fibres extend from the host brain into the hippocampal
      transplant to establish synapses with the target neurons.

PMID- 7570117
TI  - [Different effect of L-glutamate microinjection into medial or lateral habenular
      nucleu on pain threshold].
AB  - The habenulae (Hb) are related to modulation of pain sensation, but the results
      from different laboratories are inconsistant. The aim of the present
      investigation is to clarify the discrepancy. L-Glutamic acid (L-Glu) was
      microinjected into medial (MHb) and lateral habenular nucleus (LHb) on light
      anesthetized or conscious rats, and pain threshold was then determined on the
      different models of animal. The results showed that the activation of MHb
      increased TFL, whereas activation of LHb decreased TFL.

PMID- 7570118
TI  - [Effects of pentagastrin with intracerebroventricular injection on blood pressure
      and heart rate in rats].
AB  - Experiments were carried out on 84 artifially ventilated SD rats anaesthetized
      with urethane and immobilized with gallamine triethiodide. Injection of
      pentagastrin (G5) into the rat lateral ventricle resulted in a marked elevation
      in arterial blood pressure which reached its peak at 3 min (from 12.2 +/- 1.5 to
      14.1 +/- 1.7 kPa) and also a significant increase in heart rate from 435 +/- 53.9
      to 471.6 +/- 53.2 beats/min. This effect of G5 could be partially antagonized by
      injection of phentolamine (alpha-receptor antagonist, 10 micrograms) into the
      lateral ventricle, but not by propanolol (beta-receptor antagonist, 4 micrograms)
      or atropine (M-receptor antagonist, 4 micrograms). These findings indicate that
      the central effect of G5 on blood pressure and heart rate is partly mediated by
      alpha-receptor.

PMID- 7570119
TI  - [The exciting origin of guinea-pig inferior mesenteric ganglion neurons in vivo].
AB  - Intracellular recording in vivo showed that spontaneous activities of guinea-pig
      inferior mesenteric ganglion (IMG) neurons were inhibited when any one of the
      four groups of the nerves connected to the IMG was cutted or blocked, indicating
      that all the four groups of nerves sent in excitatory input. Colonic and
      hypogastric nerves convey the peripheral excitation respectively from colon and
      bladder. Intermesenteric nerve sends in peripheral excitatory input from colon
      and central from spinal cord. This finding suggests that the excitation of the
      prevertebral ganglia originates from not only spinal cord as claimed
      tranditionally, but also the peripheral organs. The latter exits stronger effect
      than the former. It seems that IMG is an integration neurocenter rather than a
      simple signal relay station from the central nervous system to peripheral
      effectors.

PMID- 7570120
TI  - [Effect of cholecystokinin and secretin on contractile activity of isolated
      gastric muscle strips in guinea pigs].
AB  - Motility of gastric strips taken from different regions of guinea pig stomach
      were simultaneously recorded in 8 tissue chambers to test the effect of
      cholecystokinin-octapeptide (CCK-8) and secretin. It was found that CCK-8 could
      increase (1) all regional circular and longitudinal muscular tension at rest, (2)
      the frequency of contractions in body, antrum and pylorus, (3) the mean
      contractile amplitude of antral circular strips, (4) the motility index of
      pylorus, but decrease the mean contractile amplitude of body and antral
      longitudinal strips. All the CCK-8 effects could not be blocked by atropine or
      indomethacin. Secretin was without effect on gastric smooth muscle activity.

PMID- 7570121
TI  - Gorham's syndrome with pleural effusion and colonic carcinoma.
AB  - Gorham's syndrome is a rare primary disorder characterised by spontaneous bone
      resorption which usually arrests spontaneously. The presence of thoracic findings
      markedly worsens the prognosis. We report a case of Gorham's syndrome with
      thoracic as well as skeletal involvement who subsequently developed colonic
      carcinoma.

PMID- 7570122
TI  - Systemic lupus erythematosus--not to be forgotten in the elderly.
AB  - A 70-year-old woman presented with a skin rash, chronic headaches, congestive
      cardiac failure, and a moderate pericardial effusion. These were attributed to
      systemic lupus erythematosus (SLE). She responded to a moderate dose of
      corticosteroids. SLE though rare in the elderly is a disorder that should not be
      forgotten.

PMID- 7570123
TI  - Tuberculosis and invasive pulmonary aspergillosis in a young woman with a
      myelodysplastic syndrome.
AB  - A 29-year-old Chinese woman developed pyrexia, multiple skin abscesses and
      bilateral fine nodular lung infiltrates about 3 months after the commencement of
      therapy for idiopathic thrombocytopenic purpura (ITP). Pseudomonas aeroginosa was
      isolated from the abscesses but multiple blood and sputum cultures, as well as a
      broncho-alveolar lavage did not yield any microorganisms. The persistence of
      fever and pulmonary infiltrates warranted an open lung biopsy which provided a
      definitive diagnosis of tuberculous-aspergillus granulomatous lung disease. Bone
      marrow re-examination revised the primary haematological disorder to that of a
      trisomy 8 associated myelodysplastic syndrome.

PMID- 7570125
TI  - Deep vein thrombosis: a study in clinical diagnosis.

PMID- 7570124
TI  - Two-dimensional echocardiographic detection of biventricular thrombi.
AB  - A 42-year-old man presented with acute myocardial infarction. The ECG on
      admission to hospital showed "Q wave" inferior myocardial infarction and "non-Q
      wave" anterior infarction. Subsequently, he was readmitted to hospital on many
      different occasions for cardiac failure. About 15 months after the patient was
      first seen, two-dimensional echocardiogram (2D echo) showed dilatation of all 4
      cardiac chambers and severe global hypokinesia of the left ventricle. In
      addition, a large echo dense mass was seen at the apex of the left ventricle and
      2 smaller echo dense masses were present at the right ventricular apex. The
      echocardiographic characteristics of these 3 masses strongly suggest that they
      represent mural thrombi. Two-dimensional echocardiographic detection of
      biventricular thrombi has rarely been described in the past. This case together
      with the previously reported case by Friedman and Buda suggest that 2D echo may
      be a valuable test for the diagnosis of biventricular thrombi.

PMID- 7570126
TI  - Infection control--a cost containment measure in the health industry.

PMID- 7570127
TI  - Use of mammography in Singapore: an overview.

PMID- 7570128
TI  - Hepatitis A updated.

PMID- 7570131
TI  - The role of information technology in health care cost containment.
AB  - There is currently global concern over rising healthcare costs which has come at
      a time when many countries are beginning to see the tangible benefits of
      implementing information technology (IT) in healthcare. By having the right IT
      infrastructure, health facilities can achieve substantial cost savings by cutting
      down on hassles and wastage through timely availability of information. This
      paper examines the areas in healthcare in which information technology has been
      demonstrated to have effectively contributed to cost savings.

PMID- 7570130
TI  - Clustered intramammary microcalcifications not associated with a mass.
AB  - Over a period of two and a half years, 36 biopsies performed for clustered
      microcalcifications not associated with a mass revealed 30 benign and 6 malignant
      lesions. Of the 30 benign cases, 4 showed histological features which are thought
      to be associated with an increased risk of developing carcinoma. As similarities
      can exist in the mammographic appearances between benign and malignant
      microcalcifications, clusters of microcalcifications showing overlapping features
      or increasing in number over time require histopathologic study as there is no
      radiologic means at present of predicting which cluster will be malignant. We
      observe that our Chinese female population has a tendency towards dense breast
      parenchyma often associated with microcalcifications, both scattered and
      clustered. The presence of these clustered microcalcifications prompts biopsy
      even though the yield for malignancy is anticipated to be low.

PMID- 7570129
TI  - Seroprevalence of antibodies against hepatitis A (anti-HAV) in Singapore: the
      NFDD experience.
AB  - At the 4th National Foundation for Digestive Disease (NFDD) Day in 1991 where
      public lectures on prevention of hepatitis and early detection of hepatocellular
      carcinoma were given, screening of sera obtained from 364 registrants for
      antibodies to Hepatitis A (IgG) was undertaken. The overall sero-prevalence rate
      was 50%, with 55% for males and 46% for females with antibodies for HAV. None of
      the subjects below 20 years old had antibodies to HAV. This rose to 16% for those
      21-30 years old and 92% for those above 61 years. This study shows that in
      Singapore, prevalence of anti-HAV antibodies rise with age and is approaching the
      low endemicity pattern that is seen in developed countries.

PMID- 7570132
TI  - Intra-articular morphine and bupivacaine for pain relief after therapeutic
      arthroscopic knee surgery.
AB  - This randomised, double-blind study compared the analgesic properties of intra
      articular injection of morphine and bupivacaine during therapeutic arthroscopic
      knee surgery. Forty male patients were randomly divided into 4 groups of 10
      patients each. Group A received intra-articular injection of 1 mg morphine
      sulphate in 20 ml saline, Group B received 20 ml of 0.25% bupivacaine while Group
      C received 1 mg morphine sulphate in 20 ml of 0.25% bupivacaine injected intra
      articularly. Group D did not receive intra-articular injection and acted as
      control. Post-operative pain was assessed by visual analogue score. The morphine
      group had significantly lower pain score compared to the control group from 4
      hours onwards throughout the 24-hour study period (p < 0.05 at 4 hours and p <
      0.001 at 24 hours). The bupivacaine group had lower pain score than the control
      group during the first 4 hours (p < 0.001 at 1 hour and p < 0.05 at 2 hours). At
      4 hours, it showed similar analgesic efficacy as morphine. There was no
      significant analgesic effect at the end of the study period. The combination of
      the two drugs resulted in satisfactory analgesia throughout the entire study
      period (p < 0.001 at 1, 2 and 24 hours and p < 0.05 at 4 hours) and appeared to
      be a simple, safe and effective analgesic technique for patients who underwent
      therapeutic arthroscopic knee surgery.

PMID- 7570133
TI  - A controlled double-blind trial of moclobemide and imipramine in the treatment of
      depression.
AB  - The aim of this study is to compare the antidepressant efficacy and side effects
      of moclobemide with imipramine (a standard antidepressant). Moclobemide is a
      reversible inhibitor of monoamine-oxidase-A (RIMA) with selectivity for the MAO
      type A isoenzyme. Thirty-two patients who met DSM-3R criteria for major
      depressive episode or dysthymia were randomly assigned to receive either
      moclobemide or imipramine in a double-blind prospective study. The results
      indicated no difference in antidepressive efficacy between the two drugs, but
      imipramine had more anticholinergic side-effects. Neither drug had significant
      effects on pulse rate, blood pressure, weight changes or blood chemistry. These
      results were confirmed by previous studies.

PMID- 7570134
TI  - Antimicrobial resistance pattern of bacteria isolated from patients seen by
      private practitioners in the Klang Valley.
AB  - Data on bacterial resistance in patients seen by general practitioners are
      usually not readily available. The objective of this paper is to present the
      antimicrobial resistance pattern of bacteria isolated from patients seen by
      private practitioners in the Klang Valley. A total of 18 clinics participated in
      this study. From mid August 1991 to end of June 1993, 2,823 specimens were
      received. Throat swabs and urine specimens constituted 56% of all the specimens.
      A large proportion of the specimens (55%) yielded no growth or just normal flora.
      The common bacteria encountered were Staphylococcus aureus (18.4%), Escherichia
      coli (16.2%), Klebsiella spp (13.7%) and Neisseria gonorrhoeae (9.3%). The S.
      aureus strains were mainly isolated from wound, pus and ear swabs. Not one out of
      the 218 strains tested was resistant to methicillin. In vitro susceptibility
      tests showed that 91% were resistant to penicillin while 23% were resistant to
      tetracycline and 13% to erythromycin. Eighty-two percent of the E. coli were
      isolated from urine. It was also the most common isolate from urine. Fifty
      percent of these strains were resistant to ampicillin, 33% to cotrimoxazole, 17%
      to cephalothin, 21% to ampicillin-sulbactam, 18% to amoxycillin-clavulanic acid
      while only 2.3% were resistant to nalidixic acid and nitrofurantoin and none to
      cefuroxime. Generally the gram negative bacilli encountered in general practice
      are less resistant to the third generation cephalosporins and aminoglycosides
      when compared to the hospital strains.

PMID- 7570135
TI  - Outpatient coronary angiography using 7 French catheters in Singapore.
AB  - PURPOSE: Out-patient coronary angiogram (OCA) is commonly performed in many
      centres using 5 or 6 French (F) catheters. Though this small catheter may reduce
      bleeding complications, manipulatability and adequate vessel visualisation are
      problems which may increase procedure time. 7 or 8 F catheters have been used in
      Caucasians. We report our experience with OCA using 7 F catheters in an Asian
      centre. METHODS: Sixty-six patients with low procedural risk were consecutively
      recruited. They were pre-medicated with oral diazepam. Selective coronary
      angiogram (SCA) and left ventriculogram were performed via the femoral artery.
      Parenteral heparin was administered after the arterial puncture. After the
      procedure, haemostasis was secured by at least ten minutes of manual compression.
      The patients were immobilised for six hours and thereafter encouraged to walk for
      about an hour. The groin was inspected by a doctor before discharge and reviewed
      the following day. RESULTS: The age ranged from 27 to 73 years with a mean of
      52.6. There were 48 men and 18 women. Seventeen patients had previous SCA or
      angioplasty. There was no significant coronary artery disease (CAD) in 26
      patients (39.4%). Thirteen patients (19.7%) had minor CAD, 20 (30.3%) had single
      or double vessel and 7 (10.6%) had triple vessel disease. The mean procedural
      time was 16.6 +/- 7.3 minutes, ranging from 7 to 54. Seven (10.6%) of the
      patients had a small haematoma prior to discharge. None of the haematoma
      deteriorated at review. We did not find sex, age, history of diabetes mellitus or
      hypertension, height, weight, body mass index, use of anti-platelet agents,
      systolic blood pressure at and after the procedure and coronary artery anatomy to
      be associated with an increased risk of haematoma. The estimated cost savings for
      a non-subsidized patient was S$285 and for a subsidized patient was S$66.
      CONCLUSION: We conclude that OCA using 7 F catheters is a safe and efficacious
      procedure in our patients.

PMID- 7570136
TI  - Extracorporeal shock wave lithotripsy monotherapy for selected staghorn stones.
AB  - OBJECTIVE: To define a subgroup of staghorn stones that is amenable to
      extracorporeal shockwave lithotripsy (ESWL) monotherapy and review the need for
      prophylactic ureteric stents. METHODS: Fifty-eight renal units with staghorn
      calculi in 56 patients (30 males and 26 females) were treated by ESWL monotherapy
      on the EDAP LT-01 lithotripter. The stones were grouped as complete staghorn (11,
      19%), partial staghorn (34, 59%) and borderline staghorn (13, 22%). Results of
      treatment were analysed in relation to subgroup and calyceal dilatation. Post
      treatment complications were studied and the influence of prophylactic ureteric
      stents examined. RESULTS: The average number of ESWL sessions was 3.1 (range: 1
      to 8). The mean follow-up period was 13 months. Stone-free rate at 10 months was
      52%. When clinically insignificant residual fragments less than 4mm were
      included, the overall clearance rate was 75%. Favourable factors influencing
      treatment outcome included smaller stone burden, peripheral distribution of stone
      mass and absence of pelvicalyceal dilatation. The overall complication rate was
      39% with urosepsis being the commonest. Complications were related to stone
      burden. More than half of the renal units with complete staghorn stones developed
      one or more complications. Auxiliary procedures were required in 18% of the renal
      units. Twenty of 39 renal units with a stone burden (sum of length and width)
      greater than 50mm had pretreatment ureteric stenting using the double-J (DJ)
      siliastic stent. A urosepsis rate of 50% was noted in those with ureteric stents
      compared to 26% in those not stented. The stents did not offer any advantage in
      preventing post-treatment obstruction by fragments. Six of 7 renal units with
      post-treatment obstruction had in-situ stents. CONCLUSIONS: ESWL monotherapy is
      suitable for selected staghorn stones. Prophylactic ureteric stents do not offer
      any advantage and may predispose to urosepsis.

PMID- 7570137
TI  - Diagnosis of deep vein thrombosis by Duplex Doppler ultrasound imaging at the
      Singapore General Hospital.
AB  - Deep vein thrombosis (DVT) of the lower extremity is the major cause of pulmonary
      embolism and chronic venous obstruction disease of the legs. However, the
      clinical diagnosis of leg vein thrombosis is notoriously difficult. Venography,
      using iodine containing contrast materials, has been the most reliable older
      method for diagnosing thrombosis. It is relatively more invasive, requires
      exposure to radiation and is not free of risks. Doppler ultrasonography has been
      shown to be highly sensitive and specific in the diagnosis of obstruction of flow
      in veins. We present 25 patients studied at Singapore General Hospital (SGH) with
      Doppler for the presumptive clinical diagnosis of DVT. Thirteen were found to
      have complete or partial obstruction of leg veins and 12 showed normal veins.
      These 12 patients were thus spared the risk and expense of long term
      anticoagulation. In experienced hands, Duplex Doppler ultrasonograph is an
      excellent diagnostic modality for the diagnosis or exclusion of significant deep
      vein thrombosis of the legs. It can be carried out safely and reliably in the
      very sick, in patients with renal failure, diabetics and the pregnant.

PMID- 7570139
TI  - Uterine perforation during elective first trimester abortions: a 13-year review.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence,
      presentation, management and outcome of uterine perforation during elective first
      trimester abortions. METHODS: We conducted a retrospective study of 40 patients,
      including 2 transferred patients, who sustained uterine perforation during
      elective abortions from January 1980 to December 1992. RESULTS: The incidence of
      uterine perforation was 0.8 per 1,000 procedures (0.08%). There were 8 (20%)
      nulliparae and 3 (7.5%) grand multigravidae. 82.5% of the cases occurred when the
      abortion was performed by medical officers or junior registrars under training.
      The commonest perforating instrument was the suction cannula (25%) followed by
      the uterine sound (22.5%) and the dilator (20%). Three (7.5%) cases were treated
      conservatively, 33 (82.5%) cases underwent emergency operation, 2 (5%) cases were
      discovered during subsequent sterilisation, and 2 (5%) cases suffered undiagnosed
      perforation and were re-admitted for emergency surgery. Morbidity included post
      operative fever (12.5%), bowel injury (7.5%), retained conceptus (5%) and wound
      breakdown (2.5%). There was no mortality. CONCLUSION: A careful assessment of the
      uterine size and position, vigilance in the use of uterine sound and dilators,
      greater care in the use of suction cannula, and experience in vacuum aspiration
      will decrease the incidence of uterine perforation during elective abortions. A
      high degree of suspicion, early diagnosis and treatment will prevent the
      potential complications that may arise from uterine perforation.

PMID- 7570142
TI  - Management of obsessive compulsive disorder.
AB  - The treatment of obsessive compulsive disorder was characterised by therapeutic
      pessimism until 25 years ago when effective treatments using behaviour therapy
      and the serotonin reuptake inhibitors were developed. At present the best
      available treatment is a combination of behaviour therapy and pharmacotherapy
      with a serotonin reuptake inhibitor. Psychosurgery is only indicated for patients
      who fail to respond to pharmacologic and behavioural treatments and who suffer
      from disabling symptoms.

PMID- 7570138
TI  - Comparison of Pseudomonas pseudomallei from humans, animals, soil and water by
      restriction endonuclease analysis.
AB  - Pseudomonas pseudomallei isolates from 62 human, 17 animal, 3 soil and 3 water
      samples were examined by genomic DNA digestion with PstI. Five major (RE I, II,
      III, IV, V) reproducible restriction patterns were observed, with most (56/62) of
      the human isolates displaying RE I (30/62), II (5/62), III (15/62), IV (4/62), V
      (2/62), and the animal (16/17), soil (2/3), water (3/3) isolates showing
      predominantly RE II profiles. Six human and one soil isolates showed patterns
      different from those of RE I to V. Restriction endonuclease analysis may be
      applied in epidemiological studies of melioidosis.

PMID- 7570141
TI  - The anatomy of the basal ganglia and Parkinson's disease: a review.
AB  - The present understanding of the anatomy of the basal ganglia has been updated.
      Recent work has produced a primate model of Parkinson's disease for study of its
      pathogenesis and treatment. In the last two decades, administration of dopamine
      agonist has been the mainstay of treatment of Parkinson's disease in the humans.
      However, recent use of dopamine-rich tissue such as adrenal gland or human foetal
      cells is opening up a new frontier for the treatment of more severe Parkinsonism.
      Nevertheless, there is still much to be learned at the basic neuroscience level
      before such procedure could be used widely in clinical practice.

PMID- 7570140
TI  - Upright tilt table testing in the evaluation of syncope.
AB  - OBJECTIVES: To review our experience with the upright tilt table test for the
      diagnosis of vasovagal syncope in a group of unselected patients with a history
      of syncope or presyncope. METHODS: 179 patients with a history of syncope or
      presyncope were subjected to upright tilt test. After carotid sinus massage to
      exclude carotid sinus hypersensitivity, the patients were tilted on a motorised
      tilt table with footplate support to an angle of sixty to seventy degrees for
      thirty minutes. If syncope was not induced, isoprenaline was then infused for a
      further fifteen minutes. A positive response was defined as fulfilling at least
      two out of three criteria: (i) syncope or presyncope similar to the spontaneous
      episodes of syncope, (ii) relative slowing of the heart rate at the onset of
      symptoms, (iii) drop of systolic pressure to less than 90 mmHg or by more than 50
      mmHg. STATISTICAL METHODS: Continuous variables are expressed as mean values +/-
      one standard deviation and analysed for statistical significance by the unpaired
      Student's t-test. Chi-squared test with continuity correction was used for
      dichotomous variables. RESULTS: Ninety-four patients (53%) were positive for
      vasovagal syncope. Fourteen patients (8%) were positive at baseline tilt. An
      additional 80 patients (45%) were positive with the use of isoprenaline. Ten
      percent of the positive responses were purely cardioinhibitory, 10% purely
      vasodepressor and 80% mixed. The commonest cardiac rhythm during a positive
      response was junctional rhythm (46%) followed by sinus rhythm (44%). Sinus arrest
      with ventricular standstill occurred in only 5%. Accelerated idioventricular
      rhythm, 2:1 atrioventricular block and ventricular bigeminy accounted for the
      remaining 5%. CONCLUSION: The upright tilt table test is useful for the diagnosis
      of vasovagal syncope.

PMID- 7570144
TI  - Clinics in diagnostic imaging (2). Juvenile gouty arthropathy with associated
      nephropathy.
AB  - A 36-year-old Chinese man presented with clinical and biochemical features of
      renal failure. He has had recurrent attacks of acute gouty arthritis since the
      age of 15 years. Present radiographic features of extensive chronic tophaceous
      gout included soft tissue masses, calcification, and typical erosions in the hand
      and feet. The condition of familial juvenile gouty nephropathy is discussed.
      Awareness of juvenile-onset gouty arthropathy should lead to early investigation,
      diagnosis and appropriate management. The complication of associated nephropathy
      may potentially be prevented.

PMID- 7570143
TI  - Management of insomnia.
AB  - Insomnia is a common problem and studies in Singapore and abroad have shown that
      up to a third of any population studied has experienced insomnia. There is also
      increasing awareness of insomnia as a health risk. Current views of the problem
      not only focus on the disturbed sleep pattern but also on the daytime
      consequences. Younger adults tend to experience sleep latency problems and older
      adults, sleep maintenance problems. Sleep varies from person to person and
      according to age. There are no normative values to help in the diagnosis of
      insomnia but some features typical of insomnia have been noted. The aetiologies
      of insomnia are diverse and must be determined in the assessment of patients.
      Treatment of insomnia is non-pharmacologic and/or pharmacologic therapy. There
      are an increasing number of studies on the various treatments and at present a
      combination of both types appears best in the long-term management of the
      problem.

PMID- 7570147
TI  - Outpatient treatment of bulimia nervosa: an illustrative case study.
AB  - The salient features of bulimia nervosa is highlighted. Essential principles of
      an effective outpatient treatment programme is illustrated using an uncomplicated
      case history. Cognitive, behavioural and psychodynamic principles are illustrated
      in the course of therapy. The treatment programme is short-term, can be
      effectively carried out by non-medical personnel under medical supervision and is
      therefore likely to be cost-beneficial compared to longer term psychotherapies
      for the treatment of this disorder.

PMID- 7570146
TI  - Chopsticks and suicide.
AB  - A case of serious suicidal attempt in a stroke patient by piercing a chopstick
      through the nostril, resulting in cerebral injury, is reported. The choice of the
      chopstick as a suicide tool is discussed in a clinical and cultural perspective.
      The potential of using chopsticks as an offensive weapon in suicidal patients is
      emphasised.

PMID- 7570145
TI  - A young man with broad-complex tachycardia.

PMID- 7570148
TI  - Atypical presentation in the elderly--case report of an acute abdomen.
AB  - An elderly woman with an acute abdomen due to a perforated peptic ulcer is
      discussed to illustrate the problem of atypical presentation of illness in the
      elderly. The importance of not dismissing non-specific symptoms and signs such as
      confusion, restlessness, abdominal distention and non-localising abdominal
      tenderness in the elderly, is highlighted. In addition, the useful radiological
      features of pneumoperitoneum are described. The need for functional assessment
      and rehabilitation are emphasised as important components in the practice of
      geriatric medicine.

PMID- 7570149
TI  - Nodular skin tuberculosis with lymphatic spread--a case report.
AB  - An unusual case of tuberculosis paronychia with skin infection of the big toe was
      recently seen in a patient returning from Kalimantan. This was complicated by
      inguinal lymphadenitis and tuberculosis abscess formation. The diagnosis was made
      on culture of the pus from the abscess and upon biopsy and histological
      examination of the skin lesion from the toe. The patient responded to surgical
      treatment and chemotherapy with ethambutol, rifampicin and isoniazid.

PMID- 7570150
TI  - CT evaluation of soft tissue and muscle infection and inflammation: a systematic
      compartmental approach.

PMID- 7570151
TI  - Gadolinium-DTPA-enhanced magnetic resonance imaging of musculoskeletal infectious
      processes.
AB  - The purpose of this study was to assess whether gadolinium-enhanced magnetic
      resonance imaging (MRI) provides diagnostic information beyond that given by
      nonenhanced imaging in the evaluation of musculoskeletal infectious processes and
      whether it can be used for differentiating infectious from noninfectious
      inflammatory lesions. Magnetic resonance images performed with and without
      intravenous gadolinium-DTPA in 34 cases in which musculoskeletal infection had
      been clinically suspected were reviewed. Infectious lesions--including
      osteomyelitis, pyarthrosis, abscess, and cellulitis--were confirmed in a total of
      22 cases: in 15 by biopsy or drainage and in 7 by clinical course. Our results
      show that gadolinium-DTPA-enhanced MRI is a highly sensitive technique in
      diagnosing musculoskeletal infectious lesions. It is especially useful in
      distinguishing abscesses from surrounding cellulitis/myositis. Lack of contrast
      enhancement rules out infection with a high degree of certainty. However,
      contrast enhancement cannot be used to reliably distinguish infectious from
      noninfectious inflammatory conditions.

PMID- 7570153
TI  - Lumbar spine in Marfan syndrome.
AB  - Lumbar spine radiographs of 28 patients with Marfan syndrome and a gender and age
      matched control group were evaluated for scoliosis and morphologic changes of the
      L2, L3, and L4 vertebrae. No patient or control subject had any serious low back
      problems. The Marfan patients showed a high incidence of scoliosis (64%). The
      incidence of lumbosacral transitional vertebra was also high (18%). The end
      plates of the vertebral bodies in the Marfan patients were more biconcave than in
      the control group. In addition, the transverse processes were longer in relation
      to the vertebral body width in the Marfan group than in the controls. These
      findings indicate that biconcave vertebral bodies can be added to the list of
      skeletal manifestations of the Marfan syndrome, and Marfan syndrome to the list
      of differential diagnoses for biconcave vertebrae ("codfish vertebrae").

PMID- 7570156
TI  - Lead arthropathy: a cause of delayed onset lead poisoning.
AB  - Patients who suffer gun shot wounds often have retained bullet fragments within
      their bodies. These are usually of no clinical consequence. We describe three
      patients with retained bullets within their hip joints. One of these patients,
      who had extensive ground intra-articular bullet fragments and secondary
      osteoarthritis of the hip, presented with signs, symptoms, and laboratory data
      consistent with lead intoxication. The bullet and metallic fragments were removed
      surgically with good clinical response. Two patients whose bullets were implanted
      entirely within the femoral head and whose joints showed smaller degrees of lead
      fragmentation had no symptoms of lead intoxication. The degree of intra-articular
      fragmentation of the bullet and the surface area of lead exposed to synovial
      fluid are emphasized as decisive factors with respect to appropriate therapy.

PMID- 7570152
TI  - Role of technetium-99m pertechnetate scintigraphy in the management of extra
      abdominal fibromatosis.
AB  - The purpose of this study was to investigate technetium-99m pertechnetate (Tc
      99m) as a tumor-scanning agent in patients with extra-abdominal fibromatosis, and
      to establish the sensitivity of this type of scintigraphy. Eleven patients with
      extra-abdominal fibromatosis were studied: all but one having postsurgical
      recurrences. Of the 11 patients, diagnosed histologically, 5 underwent repeated
      Tc-99m scintigraphic follow-up examinations. The injected 370 MBq Tc-99m gave us
      an early scintigram within 10 min and a delayed one 2 h later. For adequate
      comparison, the region of interest (ROI) of the scintigram was placed over the
      tumor. The tumor-to-background (T/BG) count ratio was computed. Extra-abdominal
      fibromatoses, even recurrences, were demonstrated scintigraphically in both the
      early and the delayed phase, in all 11 patients. The average T/BG ratio was 2.11
      in the early scintigram and 2.15 in the delayed one. The sensitivity and the
      specificity were both 100%. Tc-99m scintigraphy has proved useful in detecting
      extra-abdominal fibromatoses and in the follow-up of patients.

PMID- 7570155
TI  - Distinctive radiological features of small hand joints in rheumatoid arthritis
      and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA)
      magnetic resonance imaging.
AB  - A series of patients with clinically early inflammatory joint disease due to
      rheumatoid arthritis, psoriatic arthritis and Reiter's syndrome were examined by
      plain film radiography and magnetic resonance imaging (MRI). The spin echo T1
      weighted precontrast, T2-weighted, and, especially, T1-weighted postcontrast
      images demonstrated distinct differences in the distribution of inflammatory
      changes, both within and adjacent to involved small hand joints. Two major
      subtypes of inflammatory arthritis were shown, thus providing a specific
      differential diagnosis between rheumatoid arthritis and some patients with
      seronegative spondyloarthritis. In particular, all the patients with Reiter's
      syndrome who were studied, and half of those with psoriatic arthritis, had a
      distinctive pattern of extra-articular disease involvement. The need for a new
      classification of clinical subsets in psoriatic arthritis has been recently
      suggested. The present findings suggest that magnetic resonance imaging could be
      useful in such a reclassification of seronegative spondyloarthritis, as well as
      offering considerable potential for a reappraisal of pathogenesis and therapy. In
      this series, it was also noted that juxta-articular osteoporosis on plain film
      did not correlate with bone marrow oedema on MRI. Hence the aetiology of this
      common radiographic finding also merits further consideration.

PMID- 7570157
TI  - Plain film evaluation of bone grafting for nonunited scaphoid fractures.
AB  - OBJECTIVE: To determine how the appearance of fracture line bridging and graft
      incorporation changed on sequential plain films obtained during the healing of
      successful grafts for scaphoid nonunion. DESIGN: We identified 50 patients who
      had healed Russe bone grafts for nonunited scaphoid fractures. These patients had
      214 sets of wrist radiographs obtained 1-36 months after surgery. Each set of
      radiographs was reviewed in random order by two observers who were blinded as to
      the patient's name and the time interval since surgery. Closure of the fracture
      line and the presence of a linear lucency in each of six zones surrounding the
      graft were assessed using a three-point grading scale. PATIENTS: Forty-six men
      and four women were included in the study. Their mean age was 30 years with a
      range from 21-43 years. RESULTS AND CONCLUSIONS: With increasing time after
      surgery, there was progressive fracture line closing and disappearance of linear
      lucencies at the interfaces between the scaphoid and the graft. However, a 20% of
      the patients had a well-defined lucency in at least one of the six zones around
      the graft on their last film. Even 1 year after surgery, the fracture line showed
      no bridging on the radial side in 22% of patients and on the ulnar side in 11%.
      We conclude that after grafting, most scaphoid nonunions show progressive
      fracture line closure and graft incorporation. However, the fracture line may not
      completely close and lucencies may persist in several zones around the graft for
      more than 1 year. These radiographic appearances should be recognized as part of
      the normal spectrum of healing.

PMID- 7570154
TI  - Visualisation of subchondral erosion in rat monoarticular arthritis by magnetic
      resonance imaging.
AB  - High-resolution magnetic resonance imaging (MRI) was used to investigate antigen
      induced monoarticular arthritis (AIMA) in the rat. In sagittal, spin-echo images
      of the knee, characteristic parallel bands, in the order dark-light-dark, were
      consistently observed 5-8 days after arthritis induction; the bands ran
      concentric with, and just beneath, the femoral and tibial articular surfaces.
      Concurrent radiology, histology and MRI (chemical shift-selective imaging and
      contrast enhancement with magnetisation transfer and gadolinium) established that
      the phenomenon reflected subchondral erosion, not artefact. The outer hypointense
      band corresponded to calcified cartilage underlying the articular surface. The
      central hyperintense band reflected inflammatory matrix displacing normal
      haematopoietic tissue immediately subchondrally; here, trabecular bone had mostly
      disappeared, but adjacent articular cartilage, although under attack and lacking
      proteoglycan, appeared structurally normal. The inner hypointense band reflected
      deeper, truncated trabeculae within inflammatory matrix, layered with pallisading
      osteoblast-like cells. This study exemplifies the power of MRI for revealing
      localised joint pathology non-invasively, and shows that rat AIMA shares many
      pathological features with arthritis in human beings.

PMID- 7570159
TI  - Multicentric giant cell tumor of skeleton.
AB  - A case of multicentric metachronous GCT was presented. The clinical and
      radiographic features of multicentric GCT as reported in the literature and in
      the present case were discussed. The multiple bone involvement made therapeutic
      assessment difficult. The surgical stage as well as the location of each lesion
      were important in planning surgery.

PMID- 7570160
TI  - Benign fibrous histiocytoma of the proximal tibial epiphysis in a 12-year-old
      girl.

PMID- 7570158
TI  - Melorheostosis with an ossified soft tissue mass: MR features.

PMID- 7570161
TI  - Ewing's sarcoma of humerus with epithelial differentiation.
AB  - We report an unusual case of Ewing's sarcoma of the humerus with epithelial
      differentiation. This rare finding has recently been documented in this type of
      tumor.

PMID- 7570162
TI  - Intrathoracic fracture-dislocation of the humerus.

PMID- 7570163
TI  - Well-differentiated, low-grade osteosarcoma of the clivus.
AB  - A case of well-differentiated osteosarcoma of the sphenoid bone was reported. The
      pathological differentiation of this rare entity from fibrous dysplasia, the
      radiographic appearance, and the differential diagnosis were discussed.

PMID- 7570167
TI  - The proteolytic pathway of Lactococcus lactis.

PMID- 7570164
TI  - A case of juxta-articular myxoma of the knee.
AB  - This 9-year-old girl presented with a painful mass in the posterolateral aspect
      of her right knee. Excisional biopsy of the mass revealed a juxta-articular
      myxoma. The differential diagnosis for such an intra- or periarticular mass
      should include meniscal cyst, parameniscal cyst, ganglion cyst, juxta-articular
      myxoma, focal nodular PVNS, and desmoid tumor. Current imaging techniques do not
      allow differentiation between these benign lesions and low grade myxoid
      containing sarcoma.

PMID- 7570165
TI  - Osteosarcoma of the hard palate.
AB  - We present the appearances of a primary osteosarcoma of the maxilla in a 26-year
      old man. The role of computed tomography--specifically, sagittal and 3-D
      reconstructions--and the differential diagnosis of bone lesions occurring at this
      site are discussed.

PMID- 7570166
TI  - Generalized periarticular myositis ossificans as a complication of
      pharmacologically induced paralysis.
AB  - To our knowledge, no previous direct associations have been made between
      generalized myositis ossificans and pharmacological therapy. We report a case of
      generalized periarticular myositis ossificans associated with the use of curare
      and diazepam. The previously reported associations of myositis ossificans with
      tetanus and burns may be misleading. It is possible that it is not the disease
      process itself (e.g., tetanus, severe burn) that precipitates heterotopic
      ossification, but the treatment of these ailments. These observations suggest the
      importance of early mobilization and restrained use of immobilizing drugs.
      Further investigation is warranted with regard to the predisposing factors of
      generalized myositis ossificans and to its prevention.

PMID- 7570168
TI  - The effect of nicotine on spinal fusion.
AB  - STUDY DESIGN: An animal model of posterior lateral intertransverse process fusion
      healing in the face of systemic nicotine. OBJECTIVES: To evaluate the effect of
      systemic nicotine on the success of spinal fusion and its effect on the
      biomechanic properties of a healing spinal fusion in an animal model. SUMMARY OF
      BACKGROUND DATA: Clinical observations suggested that cigarette smoking
      interferes with the healing of bony fusion. No direct link has been made to
      implicate nicotine as a cause for impaired healing of spinal fusions or
      fractures. METHODS: Twenty-eight adult female New Zealand white rabbits underwent
      single level lumbar posterior lateral intertransverse process fusion using
      autologous iliac bone graft. Animals were randomly assigned to either receive
      systemic nicotine or receive no nicotine. Animals were killed 35 days after
      surgery. Manual testing of the fusion mass was performed to determine the fusion
      status. Each fusion mass underwent biomechanic testing. RESULTS: Fifty-six
      percent of the control animals were judged to have solidly fused lumbar spines,
      and there were no solid fusions in the nicotine group (P = 0.02). The mean
      relative fusion strength in the control group was greater (P = 0.09) than in the
      nicotine group. For the comparable stiffness figures, the control group was
      greater than the nicotine group (P = 0.08). CONCLUSIONS: This animal model
      established a direct relationship between the development of a nonunion in the
      presence of systemic nicotine. The results suggested that bone formed in the face
      of systemic nicotine may have inferior biomechanic properties.

PMID- 7570169
TI  - Does bracing affect bone density in adolescent scoliosis?
AB  - STUDY DESIGN: This is a case-control, cross-sectional analysis of bone density.
      OBJECTIVES: To determine if bracing during growth affects bone density in
      adolescent idiopathic scoliosis and whether the effect is local or systemic.
      SUMMARY OF BACKGROUND DATA: Data concerning the effect of bracing on bone mass in
      adolescents with idiopathic scoliosis are nonexistent. We were concerned that
      bone mass loss resulting from long-term brace use may be permanent and may
      predispose to problems with osteoporosis. METHODS: Healthy adolescent females (n
      = 85) with scoliosis measuring 20-45 degrees and treated either by brace or
      observation were studied. Dietary calcium, activity level, body mass index, and
      pubertal status were evaluated. Scoliosis was measured by Cobb angle. Bone
      mineral density at the hip and spine were measured by dual energy x-ray
      absorptiometry to differentiate local versus systemic effects of bracing. Lateral
      scans of the L3 vertebral body were used to minimize the influence of the
      pedicles, the effect of the scoliosis, and the interference of the ilium.
      RESULTS: Mean age, height, and weight were similar between braced and observed
      groups. After adjusting for curve, Cobb angle, body mass index, activity, and
      diet, two-way analysis of covariance showed L3 and femoral bone mineral density
      was the same for braced and observed patients, and pubertal status affected
      spinal bone mineral density but had no effect on femoral bone mineral density.
      Pubertal status and body mass index accounted for 53% of the variation in spine
      bone mineral density and was not affected by brace use. Cobb angle, curve
      pattern, activity, and diet were not associated with bone mineral density.
      CONCLUSION: Brace treatment does not adversely affect bone mass at the spine and
      hip in children with idiopathic scoliosis.

PMID- 7570170
TI  - Biologic and biomechanic evaluation of posterior lumbar fusion in the rabbit. The
      effect of fixation rigidity.
AB  - STUDY DESIGN: The histologic and biomechanic characteristics of posterior lumbar
      fusion with varying rigidity of a novel internal fixation construct in the rabbit
      were analyzed. OBJECTIVES: To evaluate this rabbit model for future studies of
      fusion augmentation. SUMMARY OF BACKGROUND DATA: Previous studies in goats and
      dogs showed internal fixation enhances spinal arthrodesis. METHODS: Twenty eight
      New Zealand white rabbits underwent a posterior midline fusion from L4 to L6.
      Some animals received autogenous iliac crest bone graft, stabilized by wiring the
      superior facets bilaterally, and supplementation with polymethylmethacrylate. The
      experimental groups were iliac crest bone graft with either no fixation, wire
      fixation, or wire and polymethylmethacrylate fixation; and no graft and either no
      fixation, wire fixation, or wire and polymethylmethacrylate fixation. Animals
      were killed 2 months after surgery, and the specimens were nondestructively
      tested biomechanically for stiffness in six modes (flexion, extension, left and
      right bending, compression, and torsion) and histologically for evidence of
      fusion, revascularization, and new bone formation. RESULTS: Fusions with either
      wire or wire and polymethylmethacrylate fixation were significantly stiffer than
      those without fixation (P < 0.05). There was no statistical difference between
      the iliac crest bone graft and wire group and the iliac crest bone graft, wire,
      and polymethylmethacrylate group in the modes tested. Nine of 14 motion segments
      receiving the stiffest construct (iliac crest bone graft, wire, and
      polymethylmethacrylate) had evidence of solid bony fusion. None of the 12 motion
      segments receiving iliac crest bone graft and wire had evidence of bony fusion,
      but five had a fibrocartilage union with some ossification present. Eight of 12
      motion segments receiving iliac crest bone graft and no fixation had
      predominantly fibrous unions with some fibrocartilage, and only one motion
      segment of 12 showed bony fusion. CONCLUSIONS: This study suggests that more
      rigid fixation produces more successful union in rabbit posterior spinal fusion.
      This model may be useful in evaluating the ability of various biomaterials to
      augment spinal arthrodesis.

PMID- 7570171
TI  - Predicting the integrity of vertebral bone screw fixation in anterior spinal
      instrumentation.
AB  - STUDY DESIGN: Using 2-week-old calf lumbar vertebrae as a model for the human
      adolescent spine, the strength and rigidity of different methods of anterior
      spinal screw fixation and the use of noninvasive techniques for predicting bone
      screw stability before surgery and screw insertional torque intraoperatively were
      investigated. OBJECTIVES: The objectives were to determine what factors most
      affect the strength and rigidity of screw fixation, to determine the strongest
      and most rigid type of screw fixation for anterior spinal instrumentation, and to
      determine if noninvasive measurements of bone density before surgery by dual
      energy x-ray absorptiometry or quantitative computed tomography and if
      intraoperative measurement of screw insertional torque can be used to predict the
      in vivo strength and rigidity of vertebral screw fixation. SUMMARY OF BACKGROUND
      DATA: Anterior spinal instrumentation is an efficient method to correct spinal
      deformities in the thoracolumbar and lumbar spine. Fewer vertebrae are
      instrumented and arthrodesed, allowing for greater spine mobility. The forces
      transmitted to each vertebra are higher, perhaps accounting for the clinical
      failure rate of 13-30% at the metal bone interface from screw cut out. METHODS:
      Quantitative computed tomography and dual energy x-ray absorptiometry were used
      to assess the bone density of 24, 2-week-old calf lumbar vertebrae. Four
      different methods of vertebral screw fixation were evaluated: unicortical screw,
      bicortical screw, bicortical screw and washer, and bicortical screws and staple.
      The maximal screw insertional torque was measured for each specimen. Each
      vertebral body-screw construct failed in a mode simulating in vivo screw cut out.
      The applied moment and rotatory displacement were recorded. Ash density was
      measured for each vertebral body after removing all hardware. RESULTS:
      Noninvasive measures of bone density varied linearly with ash density (P < 0.01).
      Screw insertional torque varied linearly with bone mineral content and bone
      mineral density (r2 = 0.50) and was correlated with the yield moment for all
      types of fixation except the staple. Density measured by quantitative computed
      tomography did not affect rigidity or yield moment. Post hoc analysis showed that
      the screw-staple construct was the strongest and most rigid form of fixation.
      CONCLUSIONS: Measurement of bone density before surgery using dual energy x-ray
      absorptiometry and intraoperative measurement of screw insertional torque can be
      used to assess the stability of anterior spinal instrumentation. A bicortical
      screw inserted through a Dwyer-type staple provided the strongest and most rigid
      form of fixation.

PMID- 7570172
TI  - Meta-analysis of surgical outcome in adolescent idiopathic scoliosis. A 35-year
      English literature review of 11,000 patients.
AB  - STUDY DESIGN: Meta-analysis of the English literature on the surgical treatment
      of adolescent idiopathic scoliosis. OBJECTIVE: To gather comparable data from a
      number of different sources and combine the data to create a larger, more
      statistically significant pool of information for the analysis of surgical
      outcome. SUMMARY OF BACKGROUND DATA: Meta-analysis is a technique of scientific
      literature review used in outcome evaluation of medical treatment. This technique
      has been applied to the surgical outcome of adolescent idiopathic scoliosis.
      METHODS: A structured literature review was performed that cross-referenced
      English literature articles pertaining to the surgical treatment of adolescent
      idiopathic scoliosis with a focus on patient-based outcomes. Measures of patient
      satisfaction were compared with process measures of care. RESULTS: A number of
      patients (10,989) were reviewed in 139 patient populations. Unspecified curve
      types (9424) and King curve types (1565) were reviewed over a 35-year period from
      1958 to 1993. Of the patients, 87.32% were studied retrospectively and 12.70%
      prospectively. Effect-weighted follow-up was 6.8 years. Only studies with
      complete process and patient data for unspecified or King curve types were
      included for satisfaction correlation calculations. Pearson product moment
      correlation for n = 33 studies, n' = 2926 patients revealed a positive r' = 0.628
      correlation between degree of curve correction and percent satisfaction per
      study. To determine the degree of curvature correction resulting in patient
      satisfaction, a stepwise multiple linear regression analysis was performed with
      level of confidence (P < or = 0.05). Of significance was that the degree of
      curvature corrected accounted for all the satisfaction variance predicted. A
      significant correction exists between degree of curve correction and percent of
      patients satisfied. The percent of correction and the Group type (either
      unspecified or King classified), did not significantly alter this prediction. The
      best predictor of satisfaction appears to be degree of curve correction according
      to these data. CONCLUSION: Patients appear to be more satisfied by the magnitude
      of curve correction rather than the percent of curve correction. The degree of
      curvature before surgery did not predict patient satisfaction. Pearsons r' =
      0.045. Satisfaction appears to be best predicted by the degree of correction only
      and not by the percent curve correction, the curve magnitude before surgery, nor
      the Group type (King, unspecified). Patient satisfaction is subjective. It does
      not reflect the benefits of surgery with respect to the future preservation of
      pulmonary function in thoracic curves nor the prevention of osteoarthritis in
      lumbar curves.

PMID- 7570173
TI  - Triggered electromyographic threshold for accuracy of pedicle screw placement. An
      animal model and clinical correlation.
AB  - STUDY DESIGN: This study consisted of a laboratory investigation of triggered
      electromyographic stimulation of pedicle screws placed in a pig spine, with a
      correlative prospective clinical series of lumbosacral pedicle screws stimulated
      in a similar fashion. OBJECTIVES: To determine the threshold of stimulus
      intensity necessary to confirm accuracy of lumbar pedicle screw placement via a
      triggered electromyographic peripheral response. SUMMARY OF BACKGROUND DATA:
      Documentation of lumbar pedicle screw placement is imperative to perform proper
      spinal instrumentation and to avoid perioperative complications. Previous
      electrophysiologic techniques using stimulation of a pedicle opening or pedicle
      screw with peripheral recording of electromyographic activity from the lower
      extremity muscles have been used to identify varying threshold values that
      indicate a break in the bony pedicle wall. METHODS: Six adult pigs had 107
      pedicle screws placed bilaterally into the pedicles of the lumbar spine. These
      screws were stimulated with an ascending stimulus intensity until a peripheral
      triggered electromyographic response was recorded. Pedicle screws were placed in
      the pig either entirely in the pedicle (Group A), medial to the pedicle without
      direct contact to the nerve root and dura (Group B), or purposely medial to the
      pedicle with direct contact to the nerve root and dura (Group C). A correlative
      clinical series of 233 pedicle screws placed in 54 patients had a similar
      intraoperative neurophysiologic technique. RESULTS: In the animal model, the mean
      threshold differences were: Group A screws 21.9 mA, Group B screws 8.5 mA, and
      Group C screws 4.2 mA (P < 0.05). Ninety-three percent of the clinical Group A
      screws had threshold stimuli less than 8.0 mA, whereas Groups B and C screws had
      a mean threshold of 3.3 mA. CONCLUSIONS: Triggered electromyographic stimulation
      is a valuable aid to determine appropriate placement of pedicle screws. We
      recommend the following interpretation of threshold stimulus intensity: > 8 mA-
      screw entirely in the pedicle; 4.0-8.0 mA--potential for pedicle wall defect; <
      4.0 mA--strong likelihood of pedicle wall defect with potential for nerve root
      and dura contact.

PMID- 7570175
TI  - The morbidity of heparin therapy after development of pulmonary embolus in
      patients undergoing thoracolumbar or lumbar spinal fusion.
AB  - STUDY DESIGN: The postoperative course of patients who developed a pulmonary
      embolus after thoracolumbar or lumbar spinal fusion treated with heparin was
      studied to quantify the morbidity risk of anticoagulation. OBJECTIVE: To compare
      the morbidity risk of heparinization with that of an alternative form of therapy-
      inferior vena cava filter placement. SUMMARY OF BACKGROUND DATA: Therapeutic
      heparinization was the current treatment of choice for patients who develop
      thromboembolic disease after surgery. Although heparin usage was reported to be
      associated with a number of complications after other orthopedic and general
      surgical procedures, no information was available to identify complications of
      heparinization after lumbar or thoracolumbar spine surgery or to define the risk
      of such complications. METHODS: Twenty-two members of the Scoliosis Research
      Society were polled to determine their experiences with the anticoagulation of
      this subset of patients. Surgeons polled had a combined experience of 250 man
      years and had performed more than 13000 thoracolumbar and lumbar spinal fusions.
      The MEDLINE database was used to review pertinent English language publications
      describing inferior vena cava filter complications, effectiveness, safety, and
      indications for use. RESULTS: Nine patients were located who fit the inclusion
      criteria of this study. Six (67%) had complications attributable to
      heparinization. Clinically significant complications of filter placement ranged
      from 0.12% to 10.1%. CONCLUSIONS: Heparinization after the development of
      pulmonary embolus in patients recently undergoing spinal fusion is associated
      with a high complication rate. The morbidity of vena cava filter placement is low
      and should be considered a treatment alternative in the treatment of patients who
      experience pulmonary embolus after surgery.

PMID- 7570174
TI  - The surgical and medical perioperative complications of anterior spinal fusion
      surgery in the thoracic and lumbar spine in adults. A review of 1223 procedures.
AB  - STUDY DESIGN: A retrospective review of 1223 thoracic and lumbar anterior spinal
      fusions was performed from 1969 through 1992. OBJECTIVES: To document the
      incidence and specific types of perspective complications related to anterior
      spinal fusions. SUMMARY OF BACKGROUND DATA: Despite the increased use of anterior
      spinal surgery, there has been little documentation of the specific types and
      frequencies of the complications associated with its use. METHODS: All Minnesota
      Spine Center patients age 18 years or older who had anterior spinal fusions
      between the levels of T1 and S1 from August 1969 to June 1992 were reviewed for
      the occurrence of perioperative complications. Surgical approach and technique
      and associated comorbidity was recorded. RESULTS: The risk of a complication was
      increased for patients over age 60 years, for women, and for patients with
      multiple preexisting health problems. Serious complications, such as death
      (0.3%), paraplegia (0.2%), and deep wound infection (0.6%) were rare. The
      complication rate for complications that were directly attributed to the anterior
      spinal surgery was 11.5%. CONCLUSIONS: Anterior spinal fusion surgery is a safe
      procedure and can be used with confidence when the nature of a patient's spinal
      disorder dictates its use. Complications are often approach specific.

PMID- 7570177
TI  - Results of surgical correction of kyphotic deformities of the spine in ankylosing
      spondylitis on the basis of the modified arthritis impact measurement scales.
AB  - STUDY DESIGN: This is a retrospective study of patient outcome in ankylosing
      spondylitis patients with fixed kyphotic deformities of the spine who underwent
      reconstructive surgery. OBJECTIVES: To measure the multidimensional effects of
      reconstructive spinal osteotomy in this patient group with a questionnaire-based
      instrument. SUMMARY OF BACKGROUND DATA: Between 1979 and 1988, 175 ankylosing
      spondylitis patients underwent operative treatment for fixed flexion deformities
      of the spine. One hundred forty-eight of these patients answered the
      questionnaire correctly and were included in the study. The others either died or
      were lost to follow-up. METHODS: The modified Arthritis Impact Measurement Scales
      with eight scales and 60 items plus six additional summative questions were
      administered at a mean follow-up period of 4.8 years (range, 2-10 years). The
      modified Arthritis Impact Measurement Scale measures eight scales--mobility,
      physical, household, daily, social activity, pain, anxiety, and depression. The
      Wilcoxon and chi-square test were used for analysis. RESULTS: Forty-seven of 60
      items showed significant improvement of activity levels or status. Only two items
      showed a significant impairment of function. Of the patients, 88.4% were very
      satisfied with the result of the operation; 60.9% were able to return to work.
      Age, sex, and type of surgical technique did not influence the results.
      CONCLUSIONS: The modified Arthritis Impact Measurement Scales approach shows
      excellent overall improvement of health status after surgery, proving the worth
      of reconstructive surgery in ankylosing spondylitis patients with fixed kyphotic
      deformities of the spine.

PMID- 7570176
TI  - The effect of different surgical releases on thoracic spinal motion. A cadaveric
      study.
AB  - STUDY DESIGN: Two separate experiments (A and B), each involving six human
      cadaveric torsos with intact rib cages and sternums, were done to determine the
      effect of two different sequences of surgical releases (at T8-T9) on thoracic
      spinal motion. OBJECTIVES: Experiment A was designed to test the effects of three
      releases in sequence from anterior to posterior, analogous to a two-stage
      operative treatment with anterior and posterior releases. Experiment B, which
      involved three releases, was designed to determine 1) if unilateral posterior
      total facetectomy alone allowed a significant increase in motion and 2) if rib
      head resection without discectomy allowed a significant increase in motion.
      SUMMARY OF BACKGROUND DATA: In the surgical treatment of thoracic spinal
      deformity, surgical release is often done to impart additional flexibility to the
      spine. Available releases include discectomy, rib head resection, and
      facetectomy. There is little work to date on the relative importance of the disc,
      rib head, and facet joint in the stability of the thoracic spine. METHODS: In
      experiment A and experiment B, the cadaveric torsos were mounted on a custom-made
      loading frame. Mechanical testing (using weights, pulleys, and digital
      goniometers) was done after each surgical release to measure the extent of
      angular rotation in the coronal plane (right lateral bending and left lateral
      bending) and in the sagittal plane (flexion and extension). RESULTS: The
      combination of rib head resection and radical discectomy provided the greatest
      increase in thoracic spinal motion. Standard discectomy alone did not allow a
      significant increase in motion. Rib head resection without discectomy did not
      allow a significant increase in motion. Unilateral posterior total facet excision
      did not allow a significant increase in motion. CONCLUSIONS: These experiments
      indicate that the combination of rib head resection and radical discectomy may be
      the optimal thoracic spinal release.

PMID- 7570178
TI  - Laparoscopic approaches to the lumbar vertebrae. An anatomic study using a
      porcine model.
AB  - STUDY DESIGN: This study described and compared retroperitoneal and
      transperitoneal laparoscopic approaches to the lumbar vertebrae in pigs.
      Technical and perioperative complications were evaluated for each approach.
      OBJECTIVES: The objective of this study was to develop a laparoscopic approach to
      the lumbar vertebrae that is associated with minimal technical and perioperative
      complications. SUMMARY OF BACKGROUND DATA: Laparoscopic techniques have been used
      extensively in many surgical fields. Recently, thoracoscopy has been used to
      perform a number of thoracic spinal procedures, including thoracic discectomy,
      and anterior osteotomy, release, and fusion. To date, there have been no
      published reports describing laparoscopic approaches to the lumbar vertebrae.
      METHODS: With all pigs positioned in left lateral recumbency, retroperitoneal and
      transperitoneal laparoscopic approaches to the lumbar vertebrae were performed in
      three pigs. Placement of the insufflation needles and trocar ports were
      determined for each approach. Dissection of the lumbar vertebrae were performed,
      and the technical and perioperative complications recorded. Radio-opaque markers
      were placed to identify the dissected lumbar intervertebral disc spaces, and
      intraoperative fluoroscopy was used to confirm marker placement. Gross anatomic
      dissections were performed after the pigs were killed. RESULTS: Loss of
      pneumoretroperitoneum resulted in surgical termination in two of three pigs
      undergoing retroperitoneal laparoscopic approach to the lumbar vertebrae. In the
      remaining pig, difficulty was encountered in mobilization of the psoas major
      muscle from the lumbar vertebrae, and significant bleeding occurred. The
      transperitoneal approach to the lumbar vertebrae resulted in rapid mobilization
      of the psoas musculature and exposure of the lumbar vertebral bodies and discs of
      L1-L6/L7. Intraoperative complications included minimal bleeding and difficulty
      encountered in mobilization of the renal vascular pedicle. CONCLUSIONS: The
      retroperitoneal approach was difficult because of the degree of muscle dissection
      required for exposure of the lumbar vertebrae. Complications associated with the
      retroperitoneal approach included loss of pneumoretroperitoneum because of entry
      into the peritoneal cavity, hemorrhage, and limited exposure of the lumbar
      vertebrae. The transperitoneal approach was easier technically, allowing
      identification and access to lumbar vertebral bodies and intervertebral discs
      from L1-L6/L7. Operative complications associated with the transperitoneal
      laparoscopic approach were minimal.

PMID- 7570180
TI  - Nerve root compression by a ganglion cyst of the lumbar anulus fibrosus. A case
      report.
AB  - STUDY DESIGN: A case report of a ganglion cyst rising from the anulus pulposus,
      causing lumbar nerve root compression. OBJECTIVES: A rare pathologic condition
      causing sciatica is described. The pathologic anatomy and the magnetic resonance
      image of the lesion is discussed. SUMMARY OF BACKGROUND DATA: A 35-year-old man
      was subjected to an abrupt twisting motion of the torso during a motor vehicle
      accident. The patient had a L5-S1 discectomy 1 year before the accident. His low
      back discomfort and right lower extremity pain were clearly exacerbated by the
      recent trauma. METHODS: Magnetic resonance imaging revealed enhancing lobulated
      epidural mass displacing the S1 nerve. RESULTS: Intraoperative findings were a
      lobulated cystic mass rising from the degenerated anulus fibrosus, determined on
      histologic examination to be a ganglion cyst. The patient noted significant
      relief of the right sciatica after surgery. CONCLUSION: The appearance and the
      signal intensity of the epidural mass appear to be important parameters in
      diagnosing the presence of a ganglion cyst of the anulus fibrous. Excision of the
      ganglion cyst is indicated in a patient who fails to respond to conservative
      treatment and where the symptoms correlate with the abnormality seen with
      magnetic resonance imaging.

PMID- 7570179
TI  - The incidence of complications in endoscopic anterior thoracolumbar spinal
      reconstructive surgery. A prospective multicenter study comprising the first 100
      consecutive cases.
AB  - STUDY DESIGN: A prospective multicenter study on 100 consecutive surgical
      procedures. OBJECTIVES: A prospective multicenter study was performed to evaluate
      the early perioperative complications in 100 endoscopic spinal procedures--78
      video-assisted thoracic surgical procedures and 22 laparoscopic lumbar
      instrumentation and fusion procedures. SUMMARY OF BACKGROUND DATA: Endoscopic
      procedures have been widely applied in general surgery for appendectomy,
      cholecystectomy, liver resection, Nissen fundoplication, colon resection, and
      hernia repairs. Video-assisted thoracic surgery is widely used for pleural
      biopsy, lung resection, and sympathectomy. This is the first large series to date
      investigating the safety and potential complications using endoscopic surgery for
      anterior decompression or fusion of the thoracolumbar spine. METHODS: Video
      assisted thoracic surgical procedures included multilevel anterior thoracic
      releases for deformity, 27 patients; anterior thoracic discectomies with spinal
      canal decompression, 41 patients; pyogenic vertebral osteomyelitis decompression,
      2 patients; and vertebral corpectomy for neurologic decompression, 8 patients.
      Mean operative time was 2 hours, 34 minutes (range, 45 minutes to 6 hours), and
      mean length of stay was 4.97 days (range, 2-21 days). Anterior laparoscopic
      interbody stabilization and fusion at L4-5 or L5-S1 was performed in 22 patients.
      The mean operative time was 4 hours, 17 minutes (range, 2 hours, 40 minutes to 9
      hours), and the mean length of stay was 5.6 days (range, 1-23 days). RESULTS: The
      most common video-assisted thoracic surgical complications were transient
      intercostal neuralgia (six patients) and atelectasis (five patients). The most
      common laparoscopic complication was bone graft donor site infection (two
      patients). There were two endoscopic cases that were converted to open
      procedures, one for extensive pleural adhesions and one for a common iliac vein
      laceration. CONCLUSIONS: The endoscopic spinal approaches proved to be safe
      operative procedures in 100 consecutive cases. There were no permanent iatrogenic
      neurologic injuries and no deep spinal infections.

PMID- 7570181
TI  - Massive osteolysis of the cervical spine. A case report.
AB  - STUDY DESIGN: This study described the course of a case of massive osteolysis
      (Gorham's disease) of the cervical spine and discussed the literature data.
      OBJECTIVES: To describe a case of massive osteolysis of the cervical spine with
      fatal outcome and to discuss the classification of the disease among osteolysis
      and its therapeutic modalities. SUMMARY OF BACKGROUND DATA: Massive osteolysis is
      a rare condition (fewer than 100 cases reported in the literature) of unknown
      etiology, which may involve any bone in the body, with a propensity for the
      shoulder and pelvic girdle. Few cases of cervical spine involvement were
      reported. METHODS: The case of a 32-year-old man with fatal progressive massive
      osteolysis of the cervical spine despite multiple attempts to achieve surgical
      stabilization was reported. RESULTS: Massive osteolysis was characterized by
      complete destruction of all or part of a bone by angiomatous tissue and may have
      represented a local disturbance of osteoclastic activity. No successful therapy
      was proposed, and the prognosis of spine involvement was very poor. CONCLUSIONS:
      Massive osteolysis is a rare condition with no successful therapy. The hypothesis
      of involvement of circulating preosteoclasts in the osteolytic process may
      suggest treatment attempts with diphosphonates because of the futility of
      standard bone grafting techniques in spine involvement.

PMID- 7570182
TI  - Hereditary multiple exostoses and cervical ventral protuberance causing
      dysphagia. A case report.
AB  - STUDY DESIGN: A case report of a patient with hereditary multiple exostosis and
      who presented with cervical ventral protuberance causing dysphagia. OBJECTIVES:
      To present this rare situation and to discuss the treatment and the result
      obtained. SUMMARY OF BACKGROUND DATA: We found in the literature only one case of
      exostosis of the cervical spine causing dysphagia. METHODS: The patient, a 16
      year-old girl, was affected by hereditary multiple exostosis, as was her father.
      The diagnosis was confirmed by radiograph, computed tomography, and magnetic
      resonance imaging, which showed a tumor in the anterior arch of the atlas. The
      patient was submitted to a transoral approach, and the tumor was excised.
      RESULTS: The patient had a good evolution 2 years after the surgery without sign
      of recurrence. CONCLUSIONS: This was a very rare situation, and the result
      validated the treatment used.

PMID- 7570184
TI  - Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible
      candidate genes for autosomal recessive familial amyotrophic lateral sclerosis.
AB  - Recently, point mutations in superoxide dismutase 1 (SOD1) have been shown to
      lead to a subset of autosomal dominantly inherited familial amyotrophic lateral
      sclerosis (ALS). These findings have led to the hypothesis that defects in oxygen
      radical metabolism may be involved in the pathogenesis of ALS. Therefore, we
      decided to analyze other enzymes involved in oxygen radical metabolism for
      possible involvement in other forms of ALS. We report here analysis of two genes
      encoding the molybdenum hydroxylases aldehyde oxidase (AO) and xanthine
      dehydrogenase/oxidase (XDH) for involvement in ALS. Of particular interest, one
      gene identified as encoding aldehyde oxidase is shown to map to 2q33, a region
      recently shown to contain a gene responsible for a familial form of ALS with
      autosomal recessive inheritance (FALS-AR). The AO gene appears to be located
      within 280,000 bp of simple sequence repeat marker D2S116, which shows no
      recombination with the FALS-AR locus. The AO gene is highly expressed in glial
      cells of human spinal cord. In addition, we mapped a gene for XDH to 2p22, a
      region previously shown to contain a highly homologous but different form of XDH.
      Neither of these XDH genes appears to be highly expressed in human spinal cord.
      This evidence suggests that AO may be a candidate gene for FALS-AR.

PMID- 7570183
TI  - Molecular characterization of a deleted X chromosome (Xq13.3-Xq21.31) exhibiting
      random X inactivation.
AB  - As a result of selection following random X chromosome inactivation in human
      females, X chromosomes with visible deletions are usually inactive in every
      somatic cell. We have studied a female with mental retardation and dysmorphic
      features whose karyotype includes an X chromosome with a visible interstitial
      deletion in the proximal long arm. Based on cytogenetic analysis, the proximal
      breakpoint appeared to be in band Xq13.1, and the distal one in band q21.3.
      However, molecular analyses show that less of the q13 band is missing than
      cytogenetic studies indicated, as the deletion includes only loci from the region
      Xq13.3 to Xq21.31. Unexpectedly, studies of chromosome replication show that the
      pattern of X inactivation is random. Whereas the deleted X chromosome is late
      replicating in some cells from all tissues studied, it is early replicating in
      the majority of blood lymphocytes and skin fibroblasts, and is the active X
      chromosome in many of the hybrids derived from skin fibroblasts. As this
      chromosome is able to inactivate, it must include those DNA sequences from the X
      inactivation center (XIC) that are essential for cis X inactivation. Molecular
      studies show that the XIC region, at Xq13.2, is present, so it is unlikely that
      the lack of consistent inactivation of this chromosome is attributable to close
      proximity of the breakpoint to the XIC. Supporting this conclusion is the
      similarity of the breakpoints to those of the other chromosomes we studied, whose
      deletions clearly do not interfere with the ability to inactivate. Our results
      show that deletions distal to DXS441 in Xq13.2 do not interfere with cis X
      inactivation. We attribute the random pattern of X inactivation reported here to
      the fact that in the tissues studied, cells with this interstitial deletion are
      not at a selective disadvantage.

PMID- 7570186
TI  - Three distinct loci on human chromosome 21 contribute to interferon-alpha/beta
      responsiveness.
AB  - The species specificity of interferons (IFNs) depends on restricted recognition
      of these ligands by multisubunit cell surface receptors. Expression of the human
      receptor subunit IFNAR in mouse cells conferred sensitivity only to one subtype
      of human IFN, IFN-alpha B. Other genes on human chromosome 21 were required for
      responses to other subtypes of type I IFN. In contrast, IFNAR expression in
      hamster cells did not confer sensitivity to any human IFN tested, including IFN
      alpha B. Using human-hamster somatic cell hybrids, we mapped the Ifnabr gene,
      encoding a ligand-binding subunit of the IFN-alpha/beta (type I) receptor, to
      human chromosome 21. Ifnabr colocalized with Ifnar to the distal region of q22.1.
      The presence of a chromosomal fragment encoding IFNABR and IFNAR was also not
      sufficient to confer sensitivity to human IFN. In contrast, hybrids carrying in
      addition the region 21q22.2 showed a full response to human IFN-alpha B,
      suggesting that a gene located in this region encodes a third factor required for
      type I IFN receptor activity.

PMID- 7570190
TI  - [Toxic colitis from the viewpoint of the surgeon].
AB  - The submitted review deals with the diagnosis and treatment of severe forms of
      toxic colitis from the gastroenterological and surgical aspect. The author
      emphasizes the importance of early diagnosis of the disease and early onset of
      conservative treatment which, however, should not exceed 72 hours without obvious
      improvement of the patient's condition. For surgical intervention the method of
      choice is subtotal colectomy with ileostomy and a mucous fistula of the
      rectosigmoid. In cases of early intervention the lethality is less than 10%; when
      the operation is late (frequently with complications) it is 30% or more. Better
      information of medical professionals on the disease is desirable.

PMID- 7570185
TI  - YAC contig mapping of six expressed sequences encoded by human chromosome 21.
AB  - Six cDNA clones from human chromosome 21 have been mapped in a set of complete
      YAC contig spanning the entire chromosome 21q. The mapping positions between two
      STSs on the YAC contig and the NotI coordinates starting from the telomere of 21q
      were determined for the cDNA clones. The YAC contig mapping positions agree well
      with those using a comprehensive somatic cell hybrid mapping panel.

PMID- 7570188
TI  - Periodicity of eight nucleotides in purine distribution around human genomic CpG
      dinucleotides.
AB  - Mammalian genomes, unlike the genomes of Drosophila and yeast, are characterized
      by CpG methylation and concomitant CpG depletion, which is caused by the enhanced
      mutation rate of 5-methylcytosine. To find out whether local nucleotide sequences
      around existing methylated CpG dinucleotides have common patterns, we analyzed a
      large population of CpG-poor regions in human DNA, which are typically
      methylated. We detected a novel periodic variation in the numbers of purine bases
      around CpGs in the noncoding parts of these sequences. This periodicity of eight
      nucleotides gradually diminished over 64 nucleotides on each side of the central
      CpG. Furthermore, the frequencies of the 5' and 3' nearest neighbors of CpGs in
      CpG-poor regions were biased towards cytosine and guanine, respectively. Such
      biased sequence contexts may have helped to stabilize CpGs against depletion
      during mammalian evolution.

PMID- 7570187
TI  - Identification of the human neuronal nicotinic cholinergic alpha 2 receptor
      locus, (CHRNA2), within an 8p21 mapped locus, by sequence homology with rat DNA.
AB  - We have identified a cosmid, at the D8S131 locus, that shows sequence homology
      with exon 2 of the rat gene for the neuronal nicotinic acetylcholine receptor
      alpha 2 subunit. A 357-bp sequence surrounding a rare cutter AscI site contains a
      152-bp region of homology. The human CHRNA2 gene is therefore positioned at the
      D8S131 locus, which has been mapped to 8p21.

PMID- 7570191
TI  - [Toxic colitis. II. Personal experience].
AB  - The author presents his own experience with the diagnosis and treatment of 19
      patients with acute manifestations of toxic colitis. Patients with ulcerative
      colitis developed toxic colitis in 11 instances. The second most frequent
      background for the development of toxic colitis was pseudomembranous colitis.
      Conservative treatment before 72 hours was successful only in two patients.
      Seventeen patients were operated at varying intervals after the onset of the
      disease (1-21 days) and subtotal colectomy was performed with ileostomy and a
      mucous fistula of the rectosigmoid. The lethality in the whole group was 10.5%.
      All patients who died (2) were from the group operated on the 5th-7th day, while
      in the groups operated on the 2nd-5th and 14th to 21st day there were no deaths.
      In the group two cases of carcinoma were detected.

PMID- 7570192
TI  - [Surgical procedures in tumors of the female breast--historical aspects].
AB  - The reflections pertain to operations of the female breast in the 20th century as
      they were introduced and abandoned at the Bulovka Clinic in Prague. The author
      emphasizes the modern concept of senology as a multidisciplinary field, where
      surgery--amputation as well as reconstruction and plastic surgery--still play a
      decisive role.

PMID- 7570189
TI  - Human cDNA clones that modify radiomimetic sensitivity of ataxia-telangiectasia
      (group A) cells.
AB  - Genes responsible for genetic diseases with increased sensitivity to DNA-damaging
      agents can be identified using complementation cloning. This strategy is based on
      in vitro complementation of the cellular sensitivity by gene transfer. Ataxia
      telangiectasia (A-T) is a multisystem autosomal recessive disorder involving
      cellular sensitivity to ionizing radiation and radiomimetic drugs. A-T is
      genetically heterogeneous, with four complementation groups. We attempted to
      identify cDNA clones that modify the radiomimetic sensitivity of A-T cells
      assigned to complementation group [A-T(A)]. The cells were transfected with human
      cDNA libraries cloned in episomal vectors, and various protocols of radiomimetic
      selection were applied. Thirteen cDNAs rescued from survivor cells were found to
      confer various degrees of radiomimetic resistance to A-T(A) cells upon repeated
      introduction, and one of them also partially influenced another feature of the A
      T phenotype, radioresistant DNA synthesis. None of the clones mapped to the A-T
      locus on chromosome 11q22-23. Nine of the clones were derived from known genes,
      some of which are involved in cellular stress responses. We concluded that a
      number of different genes, not necessarily associated with A-T, can influence the
      response of A-T cells to radiomimetic drugs, and hence the complementation
      cloning approach may be less applicable to A-T than to other diseases involving
      abnormal processing of DNA damage.

PMID- 7570193
TI  - [Subtotal colectomy in emergency situations].
AB  - One-stage subtotal colectomy is the most radical solution of ileous conditions
      caused by an obturating tumour of the left half of the colon. The authors report
      on their experience with this procedure in 10 patients operated in the course of
      three years. They emphasize the advantages such as oncological radicality,
      immediate detoxication of the organism, a favourable postoperative course with a
      low morbidity (10% dehiscences) and lethality (10%), shorter hospitalization
      period, life of the patients without a stoma, lower costs and satisfactory
      functional results. For an experienced surgeon, if perfect intensive
      postoperative care is available, this operation is the method of choice even in
      very old patients.

PMID- 7570194
TI  - [Evaluation of the quality of life in patients with stomas].
AB  - During the past five years in the Czech republic marked improvement of care as
      regards patients with stomas was achieved and thus also improvement of the
      quality of their life. The author made a survey, using questionnaires, among
      patients with stomas operated at the author's department. About half the patients
      in productive age returned to their jobs, sexual life was discontinued only in
      one third of the patients under 60 years of age. As regards social life, sports
      and travel activities in these spheres increased by 9-15%, as compared with a
      similar survey made in 1990 in the same department. 75% of the patients with
      stomas consider the stoma bearable. Lack of care of stoma patients involves in
      particular poor information on the patient's part during the perioperative period
      and as regards the social sphere.

PMID- 7570195
TI  - [Surgical wound dehiscence and a technique for laparotomy closure with continuous
      loop sutures].
AB  - The authors evaluate two groups of patients after laparotomy where during the
      postoperative period complete dehiscence of the laparotomic wound occurred. In
      the first group A the laparotomies were closed in anatomical layers by individual
      silon stitches, in group B for closure a single layer continuous PDS loop suture
      was used. After introduction of this technique the percentage of dehiscent
      laparotomies declined from 2,2% to 1,2%.

PMID- 7570196
TI  - [The vermiform appendix and its use in urology].
AB  - There are presented new possibilities of using the appendix vermiformis in
      urology: Mitrofanoff's procedure (continent appendicovesicostomy), continent
      appendix stoma performed with the MAINZ pouch technique and continent
      appendicocolostomy. There was operated on 12 pts. for the neuropathic bladder
      using the Mitrofanoff's procedure. An ischemic occlusion of the appendicostomy
      was found out postoperatively in one case. All pts. but one practise clean
      intermittent catheterization through the appendicostomy (four to six times a day)
      and eight of them (67%) are continent by day and night.

PMID- 7570197
TI  - [Laparoscopic cholecystectomy in the Czech Republic: a nation-wide study (9,439
      cases)].
AB  - The investigation is based on data obtained by means of questionnaires from 62
      surgical departments in the Czech Republic. The respondents performed to the data
      of December 31, 1993 a total of 9,439 laparoscopic cholecystectomies. Conversions
      accounted for 4.9%, some three quarters were called for by obscure anatomical
      conditions. The biliary pathways were injured (with the exception of the cystic
      duct) in 43 patients (0.46%). Peroperative biligraphy was performed in 2.6% of
      operated patients. Injuries of the digestive tract were recorded in 0.06%
      patients and injuries of blood vessels in 1.4% of patients. The morbidity in the
      group was 7.7% and the lethality 0.14% (13 patients). The authors compare the
      data with other nation-wide studies and demonstrate the advantages of
      laparoscopic cholecystectomy.

PMID- 7570198
TI  - [Combined videothoracoscopy and transhiatal esophagectomy in carcinoma of the
      middle third of the esophagus].
AB  - The authors analyze the problem of resection of the oesophagus without
      thoracotomy by means of videothoracoscopy and transhiatal technique of
      oesophagectomy in patients suffering from carcinoma of the middle third of the
      oesophagus. The authors describe a case with epidermoid carcinoma of the
      oesophagus which was resected and the oesophagus was replaced by the large
      intestine. By combination of videothoracoscopy and transhiatal oesophagectomy it
      is possible to use the advantages of resection of the oesophagus without
      thoracotomy and at the same time control optically the release of the oesophagus
      and tumour from surrounding tissues, extirpate, if necessary, paraoesophageal
      lymph nodes and check haemorrhage by endoscopic clipping of the majority of blood
      vessels. An asset of videothoracoscopy is prevention of surgical complications of
      oesophagectomy without thoracotomy.

PMID- 7570199
TI  - [Tactics and technique of primary correction of aortic arch interruption using a
      median sternotomy].
AB  - Primary correction of an interrupted aortic arch was performed in seven neonates
      aged 2 to 26 days. The operation was performed from median sternotomy with
      extracorporeal circulation using hypothermic arrest of the circulation for
      reconstruction of the aortic arch. In all neonates it proved possible to make a
      direct anastomosis of the ascendent and descendent aorta. At the same time in six
      children a defect of the ventricular septum was closed, in two the common
      arterial trunk was corrected, in one resection of subaortic stenosis was
      performed and in another child correction of the aortopulmonary window. After the
      operation three neonates died from sepsis and multiorgan failure. At present four
      patients are alive who, 10 to 20 months after operation, are in a good condition.
      All have a non-restrictive anastomosis of the aorta. Primary correction of an
      interrupted aortic arch and associated defects is preferred by the authors to two
      stage surgery.

PMID- 7570200
TI  - [Prevention and treatment of persistent perineal sinuses. Literature review and
      initial experience].
AB  - The objective of the work was to demonstrate possibilities of radical treatment
      of a perineal sinus, a very unpleasant complication after proctectomy. The
      authors prefer the use of a fasciocutaneous gluteofemoral flap based on the
      descendent branch of the inferior gluteal artery. The authors describe the whole
      surgical procedure and recommend to assemble experience with solution of
      decubital defects in the pelvic region.

PMID- 7570201
TI  - [Laparotomy closure with continuous polydioxanone sutures].
AB  - The authors describe the method of closure of laparotomic wounds by means of an
      atraumatic continuous PDS loop suture. Based on evaluation of a group of 166
      patients they appreciate the positive aspects of the technique of this suture, in
      particular the speed, easy implementation and safe closure of laparotomy. As
      regard the sewing material, they value highly the quality of atraumatic fibres
      which are firm and do not irritate the tissues.

PMID- 7570202
TI  - [Ankylosing spondylitis].

PMID- 7570203
TI  - [Outcome of patients with chronic systemic lupus erythematosus].
AB  - We analyzed data on 69 Japanese patients who had been affected with systemic
      lupus erythematosus (SLE) for more than 10 years to clarify the clinical and
      social features of the chronic phase of this disease. There were 3 men and 66
      women. Mean age at disease onset was 24.3 years, and the mean duration of disease
      was 17.4 years. In these patients, the mean number of relapses was 1.5, and the
      mean duration of the relapse was 4.7 years. These patients were receiving
      prednisolone at a mean dosage of 9.2 mg/day. While only 4 patients were thought
      to be in the active disease stage at the time of evaluation, hypercholesterolemia
      was present in 33.3% (20 patients out of 60) and 64. 3% (27 patients out of 42)
      showed a decrease in bone mineral content by DEXA method. Ten patients out of 69
      patients (14.5%) had aseptic necrosis of the head of the femur (ANF). ANF was
      related to the relapse and the administration of immunosuppressant in the initial
      therapy. Seventeen female patients had gotten married after the onset of SLE and
      14 patients became pregnant and gave birth. Of the 9 deaths that occurred, only 3
      cases were thought to be due to SLE. Two patients died suddenly, and there was 1
      case of acute heart failure. Mean age at death was 39.8 years old. However, data
      suggest that many patients in the chronic phase of SLE may have a reasonably high
      quality of life, despite the disease.

PMID- 7570204
TI  - [The relationship between genotypes of HLA-DRB1 alleles and progression of bony
      destruction changes of rheumatoid arthritis].
AB  - The relationship between genotypes of HLA-DRB 1 alleles and the progression of
      bone destruction of RA patients was assessed. The genotypes of the HLA-DRB 1
      alleles were determined in 329 Japanese patients with seropositive RNA by
      polymerase chain reaction and allele-specific oligonucleotide probe techniques.
      We regarded HLA-DRB 1* 0101, 0401, 0404, 0405, 1001 and 1402 as susceptible
      alleles of RA and classified the patients into three groups. The s/s group
      consisted of those with susceptible factors in both of the HLA-DRB 1 alleles. The
      s/n group was made up of those having one susceptible factor and one non
      susceptible factor. The n/n group consisted of those possessing two non
      susceptible factors. The grading of radiographic change that was evaluated by
      Larsen's criteria compared with the genotyped results. In the result, the median
      years taken to development to grade III, IV and V were significantly shorter in
      the s/s groups compared with that in the s/n and n/n groups. Thus, genotyping of
      HLA-DRB 1 can be a useful prognostic market in the progression of bone
      destruction of RA.

PMID- 7570206
TI  - [Clinical significance of IgG rheumatoid factor in patients with rheumatoid
      arthritis].
AB  - We studied 135 patients with rheumatoid arthritis (RA) from February 1991 through
      June 1992 (mean period: 9 months) to measure serum IgG rheumatoid factor (IgG-RF)
      by the method of enzyme linked immunosorbent assay. In order to evaluate clinical
      significance of serum IgG-RF we compared the level of IgG-RF with some of the
      clinical and laboratory markers including disease activity index of RA and titers
      of IgM rheumatoid factor (IgM-RF) and IgA rheumatoid factor (IgA-RF). Positive
      IgG-RF (more than 2.0 on IgG-RF index) was observed only in 22.2% (30 patients)
      with the examination of the first collected serum samples but was increased to
      41.5% (56 patients) by the case of total test samples. The number of patients
      with positive IgM-RF or positive IgA-RF test was significantly smaller in
      seronegative patient group than in seropositive patient group, whereas IgG-RF
      test showed no significant differences between these two groups. These indicate
      usefulness of consecutive test of IgG-RF for diagnosis of RA especially in
      seronegative patients. The mean of total score indicating radiographic bone
      destruction by Sharp's modified method was significantly higher in positive
      patients than in negative patients of IgG-RF. Multivariate analysis showed
      positive correlations between serum IgG-RF levels and erythrocyte sedimentation
      rates as well as between serum IgG-RF levels and Lansbury's indexes. These
      results suggest that the test of serum IgG-RF level is beneficial for daily
      management of patients with RA.

PMID- 7570205
TI  - [Bone mineral density of the radius in patients with rheumatoid arthritis
      measured by dual energy X-ray absorptiometry].
AB  - Bone mineral density (BMD) of the radius was measured in 181 female patients with
      rheumatoid arthritis (RA) and 255 control subjects using dual energy X-ray
      absorptiometry (DXA). The BMD of RA patients was assessed according to patients'
      age and menopause and was compared with age-matched controls for various activity
      factors of RA and duration of the disease that might correlate with BMD. At
      stages I and II of premenopausal RA, generalised osteoporosis was not observed.
      At stages III and IV, the BMD decreased considerably in premenopausal RA patients
      at age of 45 years or older. There were significant correlations between the BMD
      of postmenopausal RA and all factors examined, many of which did not affect
      premenopausal RA. These results suggest that osteoporosis of female patients with
      RA is influenced only slightly by the disease itself, but it is secondary
      osteoporosis induced by decreased activities of daily living due to RA.

PMID- 7570207
TI  - [Fracture threshhold of rheumatoid arthritis patients].
AB  - The Bone mass measurement had been difficult while the fracture risk of the
      rheumatoid arthritic patient had been depended on osteoporosis. Recently, the
      accuracy of bone mass measurement became reliable that the adequate data could be
      obtained from the patients. This study shows the fracture threshold of rheumatoid
      patients by obtaining the bone mass density of those who had been suffering from
      fracture by DEXA. Twenty two limbs of 21 female patients were affected, average
      age of 65 and duration of 18 years, and the sites of fracture were femoral neck
      in 9 cases and humeral neck in 4 cases (62% of the fracture). The BMD of the
      spine in these patients shows. 828 g/cm2 which was below -3.4 sd of the normal
      japanese female and thought to be a fracture threshold in RA patients. The risk
      factors of the fractures in RA were ADL in the limbs, history of total joints
      arthroplasty and low body mass index.

PMID- 7570208
TI  - [Prognosis and outcome of rheumatoid arthritis--10 to 16 years of anti-rheumatic
      therapy].
AB  - One hundred twenty-eight rheumatoid arthritis (RA) patients were followed up over
      a long period of time (mean, 13.3 years; range, 10-16 years) in order to
      determine the role of pharmacotherapy in RA. Patients were aged 48.2 years on the
      average (23-79 years) and the mean RA duration was 7.8 years (0-58 years) upon
      initial visit to this unit. Although pharmacotherapy was effective in improving
      Lansbury's activity index and ESR, articular bone and cartilage destruction and
      functional impairment progressed gradually, resulting in the need for total hip,
      knee or ankle arthroplasty in 46 (96 joints) of the 128 patients. This finding
      indicates that current pharmacotherapy for RA has limitations in that it cannot
      completely prevent joint destruction and resulting functional impairment. This
      suggests that new therapeutic modalities, including new drugs, are necessary.
      Efforts were also made to determine factors which affect the prognosis of RA. The
      prognosis seemed pessimistic in RA patients with high activity and rheumatoid
      factor (RAPA) levels, long duration of illness, high Larsen scores and advanced
      functional impairment at the time of initial active therapy. It appeared
      necessary to maintain Lansbury's activity index at 30% or below in order to
      obtain a good prognosis.

PMID- 7570209
TI  - [Detection of anti small nuclear ribonucleoprotein antibody in patients with
      collagen disease--a comparison of sensitivities of four methods].
AB  - OBJECTIVE: To compare the sensitivity of four techniques that can detect the
      presence of anti small nuclear ribonucleoprotein (snRNP) antibodies. MATERIAL AND
      METHOD: Sera from eighty three patients with connective tissue disease were
      positive for antinuclear antibody by indirect immunofluorescence test. Patients
      consisted of 30 cases of systemic lupus erythematosus, 19 of rheumatoid
      arthritis, 9 of mixed connective tissue disease, 8 of systemic sclerosis, 3 of
      polymyositis, 13 of Sjogren syndrome, 1 of unclassified connective tissue
      disease. Four methods including double immunodiffusion (DID), enzyme linked
      immunosorbent assay (EIA), immunoprecipitation (IP) and immunoblotting (IB) were
      compared concerning their sensitivities of detecting anti-Sm and anti-RNP
      antibodies in these sera. RESULTS: Overall sensitivities for detecting the
      presence of each antibody were similar among four methods (DID: 32/83, EIA:
      43/83, IP: 44/83, IB: 35/83). Concordance ratio of positive patterns between DID
      and EIA was 63/83 (81.9%). However, both EIA and IP could detect anti-U1 RNP
      antibody with higher sensitivity than DID. Although EIA seemed to detect anti-Sm
      antibody most sensitively in all methods, a coincidental decrease of specificity
      might be considered. IB could not classify anti-snRNP antibodies into anti-Sm
      and/or anti-RNP antibody because these antibodies might share some antigenic
      peptides of snRNP. Analysis of RNA in immunoprecipitate could not discriminate
      anti-RNP antibodies from anti-Sm antibodies because of shared RNA epitopes (e.g.,
      U1-RNA, U1U2-RNA). CONCLUSION: These results suggested that EIA might be the most
      suitable method for detecting anti-RNP antibody and that several methods should
      be combined for detecting anti-Sm antibody.

PMID- 7570210
TI  - [Detection of myocardial lesions by dipyridamole thallium-201 scintigraphy in
      patients with rheumatoid arthritis].
AB  - Dipyridamole Thallium-201 (T1) scintigraphic studies to evaluate microcirculation
      of the heart were performed in 54 patients with rheumatoid arthritis (RA) who had
      neither cardiac complaints nor myocardial damages on ECG. Twenty seven of 54 RA
      patients showed some perfusion defects in this study. The values of ESR, CRP and
      rheumatoid factors of IgM and IgG classes were significantly higher in these
      patients with perfusion defect comparing with those in the rest of RA patients
      with normal perfusion. The scintigraphic perfusion defects improved relating with
      the reduction of inflammatory activities of RA. The histological specimens of
      heart in 12 RA autopsy cases were reviewed to study the etiology of these
      perfusion defects. In 7 of 12 cases, microvasculitis and microthrombosis were
      observed without any macroscopic findings compatible with myocardial infarction.
      Our results suggest that RA patients have frequently microcirculatory
      disturbances in the heart due to microvasculitis without any clinical symptoms of
      ECG changes.

PMID- 7570212
TI  - [A case of polymyositis associated with extensive disturbance of cardiac
      conduction].
AB  - We report a case of polymyositis with extensive disturbance of the cardiac
      conduction system. A 55-year-old woman had received corticosteroids for the
      treatment of polymyositis for six years. She was admitted to our hospital because
      of palpitations and vertigo. Abnormalities on electrocardiogram (right
      bundlebranch block, right axis deviation, and atrioventricular block) and
      prolonged H-V time on His bundle electrogram revealed extensive disturbance of
      the cardiac conduction system. Myocardial pathology showed perivascular fibrosis
      and fatty infiltration. As shown is this case, patients with polymyositis often
      develop severe cardiac disorders. Therefore, the attention should be paid to the
      cardiac condition of there patients.

PMID- 7570213
TI  - [A case of melorheostosis with linear sclerodermatous skin changes].
AB  - A 69-years old Japanese woman complained of pain in the left elbow joint and
      thickened skin over the left upper limb. The pain had been present for 20 years,
      and the thickened area of the skin gradually enlarged during this period. Her
      left elbow joint showed some limitation of motion. There was no record of any
      similar condition in her family history. Radiographs of the left limb showed
      cortical hyperostosis extending from the middle of the left humerus to the distal
      end of the radius. Radiographs of the other limbs were normal. A technetium 99m
      methylene diphosphonate bone scintigraphy revealed increased uptake in the areas
      of radiographic hyperostosis. The diagnosis of melorheostosis was made. Skin
      biopsy of thickened area was performed. The epidermis was normal, and
      proliferation of normal-appearing collagen fibers into the subcutaneous fat was
      noted. No inflammatory changes were found. The cause of sclerodermatous skin
      changes was thought to be not by linear scleroderma but by melorheostosis. In
      cases of linear sclerodermatous changes, melorheostosis as its origin should be
      considered.

PMID- 7570211
TI  - [The validity and reliability of a Japanese version of Arthritis Impact
      Measurement Scales in patients with rheumatoid arthritis].
AB  - A Japanese version of Arthritis Impact Measurement Scales (Japanese-AIMS) was
      developed after the original AIMS Version 2 (AIMS 2). We then conducted a Quality
      of Life measurement of 691 patients with Rheumatoid Arthritis (RA) with this
      newly developed questionnaire. Based on the data collected, the validity and
      reliability of the Japanese-AIMS was examined. The validity of the Japanese-AIMS,
      which was assessed by the examination of internal consistency among items and
      through factor analysis, was almost comparable with that of the original AIMS 2.
      QOL scales were also validated using internal standards based on the subject's
      responses to other items in the questionnaire. The test-retest reliability, which
      was the correlation of scale scores between two tests administered 4-5 weeks
      apart, was slightly lower than the original one. We conclude that the validity
      and reliability of the Japanese AIMS were comparable with those of the original
      one, though there could be possibly improved by the minor revision of phrasing.
      The large scale QOL measurement study with RA patients is under way, using the
      Japanese-AIMS with minor revision.

PMID- 7570214
TI  - [Multiple colonic ulcers in a patient with Sjogren's syndrome].
AB  - A 25-year-old female with Sjogren's syndrome was admitted to our hospital because
      of fever and abdominal pain. Multiple colonic ulcers were demonstrated by
      gastrographin enema and colonoscopy. Histological examination revealed the
      presence of necrotizing vasculitis in the submucosal region. Large dose of
      prednisolone (60 mg/day) brought a prompt relief of her symptoms and an
      improvement of positive inflammatory signs. Pseudoaneurysm in the arteria colica
      media, which had been demonstrated by abdominal selective angiography at the time
      of diagnosis, became extinct after the steroid treatment. Healing of ulcers were
      also noted by colonoscopy. A variety of extraglandular symptoms has been reported
      in Sjogren's syndrome. Multiple colonic ulcers due to vasculitis are rarely
      complicated but may have a great impact on the prognosis of the disease.

PMID- 7570215
TI  - [Generalized angitis and recurrent infection associated hemophagocytic syndrome
      in a girl with XXX syndrome].
AB  - We have encountered a case of a girl with XXX syndrome who had infection
      associated hemophagocytic syndrome (HPS) recurrently. The patient presented hyper
      gammaglobulinemia during the clinical course and developed IAHS probably because
      of infection with Rubella virus and EB virus each as a trigger. Diseases that
      cause abnormality in X chromosome are said to present immune abnormality such as
      SLE in many cases. It is possible that the excessive X chromosome in this cases
      partially concerned with such as an immune abnormality as to cause recurrent
      IAHS.

PMID- 7570216
TI  - [Rehabilitation in rheumatoid arthritis (RA) patients--assessment of effects of
      rehabilitation based on activities of daily living (ADL)].
AB  - The 37 hospitalized RA patients undergoing rehabilitation (for 4 weeks) were
      evaluated on effects of rehabilitation by comparing scores of ADL at the time of
      admission and discharge. Items of ADL were composed of 32. Items of ADL which
      were likely to be disabled were related to those of ADL which were influenced by
      rehabilitation (r = 0.7412, p < 0.01). From this result, 11 items of ADL which
      were likely to be disabled and influenced by rehabilitation could be selected in
      order. Usefulness of these selected items of ADL on evaluation of rehabilitation
      was admitted.

PMID- 7570217
TI  - [Collagen genes and skeletal disorders].

PMID- 7570220
TI  - Perspectives on ambulatory blood pressure monitoring.

PMID- 7570221
TI  - Insurance industry and HIV/AIDS.

PMID- 7570219
TI  - [Establish the optimal dosage of TSA-234 (rhSOD) in the treatment of
      osteoarthritis].

PMID- 7570222
TI  - HIV testing protocol: so near but so far.

PMID- 7570218
TI  - [Rheumatoid arthritis and quality of life].

PMID- 7570223
TI  - HIV/AIDS activists want blacklist for discriminators.

PMID- 7570224
TI  - Cancer in South Africa.

PMID- 7570225
TI  - Shaping the health of the nation. Selections from the 1994 Budget Speech by Dr
      Nkosazana Zuma, Minister of Health.

PMID- 7570227
TI  - Medical education--the time has come.

PMID- 7570226
TI  - Improving the cost-effective and rational utilisation of medicines in South
      Africa.

PMID- 7570229
TI  - Pressure immobilisation for snakebite in southern Africa remains speculative.

PMID- 7570228
TI  - Prevent sports sponsorship by the tobacco industry.

PMID- 7570230
TI  - A review of the German national health insurance system.

PMID- 7570231
TI  - Ambulatory paediatric surgery. The development of a day-care surgical centre.
AB  - Ambulatory surgery has become an important component in the provision of surgical
      care. In 1987 a day-case surgical unit was established at Red Cross War Memorial
      Children's Hospital, Cape Town. Experience over a 6-year period (1987-1992) is
      reviewed in relation to the nature and total number of surgical procedures, pre
      operative preparation, daily utilisation of the facility, postoperative care and
      complications. During this period 16,538 patients (mean age 3 years) were
      operated on in the unit. Nine surgical disciplines participated. Pre-operative
      assessment and preparation reduced the rate of cancellations on the day of
      surgery to less than 6%, with a 90% effective use of schedules operating time.
      Scarce nursing resources were also maximally utilised. Most procedures took less
      than 30 minutes and only 0.8% exceeded 1 hour. The average ward stay was 6 hours.
      No major complications were encountered and acceptance by patients and parents
      was excellent. Only 16 children who were not scheduled to do so needed to stay in
      hospital overnight. Recommendations to establish and improve day-stay surgical
      services are presented. It is concluded that a practical, efficient service can
      be established and that the authorities should be encouraged to expand
      appropriate facilities.

PMID- 7570232
TI  - Pharmaco-economic assessment of the HMG-CoA reductase inhibitors.
AB  - OBJECTIVE: To perform a comparative pharmaco-economic assessment of two HMG-CoA
      reductase inhibitors. DESIGN: A cost-effectiveness analysis was employed using
      comparative efficacy data from selected clinical trials. A comprehensive
      international literature search formed the basis for this selection. Criteria for
      inclusion of clinical trial results in the analysis were set a priori.
      Acquisition costs used were the recommended reimbursement prices as at September
      1994. MAIN OUTCOME MEASURES: Two outcome measures are reported: (i) the
      comparative cost-effectiveness in lowering blood lipid concentrations; and (ii)
      the comparative cost-effectiveness of the medicines when used to achieve a
      predetermined therapeutic goal. RESULTS: The average cost per 1% decrease in
      total cholesterol is 21.9% higher on 10 mg pravastatin daily than on 10 mg
      simvastatin daily. Similarly the average cost per 1% decrease in low-density
      lipoprotein (LDL) cholesterol is 23.1% higher on 10 mg pravastatin than on 10 mg
      simvastatin daily. This difference is consistent throughout the dosage range. The
      use of incremental doses of simvastatin monotherapy in order to reach a
      predetermined therapeutic goal (LDL < or = 4.14 mmol/l) is more cost-effective
      than an equivalent pravastatin dosage regimen. Total treatment costs for
      simvastatin-treated patients are 3.5% less than for pravastatin-treated patients.
      More patients on simvastatin are successfully treated; the difference in overall
      treatment costs per successfully treated patient is 27.9% in favour of
      simvastatin. Sensitivity analysis shows these results to be stable under extreme
      scenarios. CONCLUSIONS: This analysis employed objective comparative efficacy
      data obtained from peer-reviewed sources to compare the economic and clinical
      outcomes of simvastatin and pravastatin in the treatment of
      hypercholesterolaemia. The acquisition cost of simvastatin is 10.3-22.8% higher
      than an equivalent milligram dose of pravastatin, depending on the dosage used.
      However, because of the greater milligram potency of simvastatin, it is a more
      cost-effective alternative. Simvastatin therefore provides better value for money
      than pravastatin in lowering lipid levels in clinical practice.

PMID- 7570233
TI  - Tobacco advertising in South Africa with specific reference to magazines.
AB  - RATIONALE: A ban on tobacco advertising forms an integral component of tobacco
      control strategies, and needs to be considered in South Africa as a matter of
      urgency. OBJECTIVES: To obtain baseline data on tobacco advertising expenditure
      in the South African media, and to compare brands used to target different groups
      in magazines. METHODS: Advertising expenditure (totals and tobacco-related) for
      1991 and 1993 was obtained from Adindex. Ten magazines, each with circulations of
      over 100,000, directed at four different target groups, were selected. For 3
      months in 1993, total and tobacco advertising expenditure, brand placement and
      magazine demographics were determined. RESULTS: Tobacco-related expenditure
      constituted 4.8% of the R3 billion spent on advertising in 1993. Print (including
      magazines) and radio together accounted for 72% of all tobacco advertising, while
      cinema and outdoor advertising were most dependent on the tobacco industry for
      revenue. Annualised advertising spending for the 10 magazines reached an
      estimated R230 million, of which tobacco 'adspend' accounted for 6.4%. The
      highest percentage of tobacco adspend (20.3%) was for a men's 'soft-porn'
      magazine. For 26 of 30 issues studied, tobacco adverts were on the back cover.
      Brand targeting was evident in black, women's, and family magazines. There was
      not a single feature article on the adverse effects of smoking on health in any
      of the magazines during the 3-month period. Only 2 magazines had single sentences
      in their health columns mentioning that smoking was bad for health. In a third
      magazine, one opinion piece devoted a full page to criticising the anti-tobacco
      lobby! CONCLUSION: Tobacco advertising, through radio and outdoor advertising,
      reaches children and illiterate communities in peri-urban and rural areas.
      Tobacco advertising in magazines targets specific consumers, such as blacks and
      women. For most magazines, tobacco adspend constitutes less than 10% of the
      total. A total ban on tobacco advertising in the media in general and certainly
      in magazines would not have adverse economic effects and would promote health.

PMID- 7570234
TI  - Decreasing asthma morbidity.
AB  - Apart from the optimal use of drugs, various supplementary methods have been
      tested to decrease asthma morbidity, usually in patients from relatively affluent
      socio-economic backgrounds. A study of additional measures taken in a group of
      moderate to severe adult asthmatics from very poor socio-economic backgrounds who
      had had on average only 5 years of schooling, is reported here. The additional
      methods were selection of patients who could successfully use a metered dose
      inhaler and prescription of other forms of administration for those who could
      not, with regular repeat checking of the techniques of aerosol use, use of
      theophylline blood level monitoring to improve the basis for discussing drug non
      compliance with patients, and repeated explanation to patients why regular
      medication and clinic attendance are essential. These measures resulted in a
      significant improvement in morbidity, whereas no such improvement was found in a
      control group.

PMID- 7570235
TI  - Retrospective analysis of snakebite at a rural hospital in Zululand.
AB  - Aspects of the epidemiology and clinical features of 81 consecutive patients
      admitted with snakebite to a rural hospital in Zululand are reviewed. Most bites
      occurred during the hot season, 40% in children under 10 years of age. Thirty per
      cent of bites occurred at night. Most bites showed features of local envenoming
      only, but systemic features (neurotoxicity and haemorrhage) were encountered.
      Snakebite caused significant morbidity and mortality. Thirty-one per cent of
      admissions needed surgery; almost 50% needed more than one operation. Five per
      cent, all children, died. The extent of local envenoming on admission proved to
      be a highly sensitive indicator of risk of worsening of local envenoming, and of
      the development of systemic signs. The analysis has allowed the development of
      rational guidelines on the management of snakebite in this hospital which, it is
      hoped, will reduce mortality rates, and has identified several areas warranting
      further research.

PMID- 7570236
TI  - Rhinogenic subdural empyema in older children and teenagers.
AB  - Forty-five patients under the age of 20 years with rhinogenic subdural empyema
      were treated at Groote Schuur Hospital and Red Cross War Memorial Children's
      Hospital between 1979 and 1991. Thirty-two were male and 13 female. The majority
      were between 13 and 19 years of age. Headache was the predominant symptom in 41
      patients. Vomiting occurred in 15 and 21 presented with seizures, 2 in status
      epilepticus. Thirty had swinging pyrexias and 26 neck stiffness while only 14 had
      focal neurological signs. Swelling of the face or orbit was seen in 24. Twenty
      two had depressed levels of consciousness and 7 had Glasgow Coma Scale (GCS)
      values below 11/15. White cell counts and erythrocyte sedimentation rates were
      raised in all cases. Twenty-three patients underwent lumbar punctures despite the
      inherent danger in this procedure. Cerebrospinal fluid analysis showed a
      pleocytosis in all cases; no organisms were cultured in any of the specimens. The
      diagnosis in all cases was made by contrast-enhanced computed tomography. Twenty
      five patients underwent multiple burrholes, 9 small craniectomies and 11
      craniotomies. Thirty-four patients made an excellent recovery. All of the 6
      patients who died had GCS values below 11 at the time of their surgery.

PMID- 7570237
TI  - Dust and pneumoconiosis in the South African foundry industry.
AB  - The objectives of this study were to estimate the extent of occupational health
      monitoring for dust and pneumoconiosis in the foundry industry and to assess dust
      levels and the prevalence of pneumoconiosis in a group of foundries. In only 13
      (16%) of the 82 foundries that responded to a postal questionnaire were regular
      periodic full-sized chest radiographs done. Dust levels were measured every 3
      years or more frequently in 20 foundries (24%). An uncontrolled dust hazard was
      evident in all 9 foundries surveyed between 1983 and 1992. The prevalence of
      silicosis ranged from 0% to 10.3% and increased with duration of service. The
      study provided convincing evidence of neglect of occupational health by the
      foundry industry.

PMID- 7570238
TI  - Constipation, purgatives or the knife? A 19th-century dilemma.

PMID- 7570240
TI  - The role of culture in primary health care. Two case studies.
AB  - The purpose of this article is to show the importance of traditional healers in
      primary health care (PHC) services. Most countries, despite adopting PHC, have
      not incorporated traditional healers into this service. The article also
      illustrates how traditional healers fulfil three of Morrell's four PHC
      objectives, and how incorporating traditional healers into health services will
      fulfil the fourth objective. The first contact between a black African patient
      and health care services usually takes place in the traditional healing system.
      Therefore health workers should realise that the traditional care system is
      important if PHC is to succeed. Traditional healers are the most important
      primary health care service in an African setting. This is highlighted by 2 cases
      described in the article.

PMID- 7570239
TI  - Fatal Capnocytophaga canimorsus (DF-2) septicaemia. A case report.
AB  - A 45-year-old man died 2 months after being bitten on the hand by a dog. He
      developed the rare but characteristic clinical picture of fulminant septicaemia
      and peripheral gangrene caused by a Gram-negative bacillus, Capnocytophaga
      canimorsus, previously known as dysgonic fermenter type 2 (DF-2), which is an
      occasional commensal in the oral flora of dogs and cats. This disease must be
      anticipated and dog bites appropriately managed to avoid the mortality associated
      with infection by this micro-organism. Initial treatment includes appropriate
      prophylactic antibiotics and debridement, while early exchange transfusion and
      emergency amputation may be of value in fulminant cases.

PMID- 7570241
TI  - Management of childhood and adolescent asthma. 1994 consensus. South African
      Childhood Asthma Working Group.
AB  - OBJECTIVE: To make recommendations regarding the treatment of chronic asthma to
      achieve effective control; to emphasise that asthma is a clinical diagnosis; to
      stress the central role of inflammation in asthma; to recommend alternative
      agents for practice where certain drugs are not available; and to address new
      agents that have been introduced for the treatment of asthma. OPTIONS: A new
      severity grading of mild, moderate and severe asthma is proposed to aid in the
      selection of medication. This severity assessment uses four features; attack
      frequency, nocturnal symptom frequency, hospital admissions and peak flow. Since
      asthma can vary with time, regular reassessment with a view to reassignment of
      individual grading is necessary. OUTCOMES: Goals of effective control strive to
      ensure that the asthmatic leads a normal life free from symptoms with regular
      school attendance, restful sleep, normal growth and development, minimal acute
      attacks and avoidance of hospital admissions. EVIDENCE: Previous local and
      international consensus statements. BENEFITS, HARMS, COSTS: Early diagnosis,
      accurate grading and effective control reduce morbidity and mortality and will be
      cost-saving. Pharmaco-economic evaluations of the cost of asthma show that
      medications per se represent a small percentage of the overall cost of asthma.
      RECOMMENDATIONS: Inhaled therapy is preferred, even in young children, as aerosol
      devices for all ages are available. Mild asthma is treated with intermittent
      short-acting beta-agonists, moderate asthma with regular cromoglycate and severe
      asthma with regular inhaled steroids. Environmental control, specialist referral
      and hazardous and unnecessary therapy are also addressed.

PMID- 7570242
TI  - Is optimal management of childhood asthma achievable in South Africa?

PMID- 7570243
TI  - Bringing down the birth rate.

PMID- 7570245
TI  - Underdiagnosis of childhood cancer.

PMID- 7570244
TI  - Rethinking medical education.

PMID- 7570247
TI  - Recurrent herpes zoster and high-dose inhaled steroids for asthma.

PMID- 7570248
TI  - Steroid-induced osteoporosis.

PMID- 7570246
TI  - Promote the community health worker.

PMID- 7570249
TI  - Electrotherapy for snakebite.

PMID- 7570252
TI  - Psychotropic medication usage at Lentegeur Hospital, Cape Town.

PMID- 7570250
TI  - Speaking out on working conditions.

PMID- 7570251
TI  - Speaking out on working conditions.

PMID- 7570253
TI  - Screening for carcinoma of the oesophagus.

PMID- 7570254
TI  - [Anti-HCV antibodies in chronically dialyzed uremic patients. 1-year follow-up
      study].
AB  - The sera of 109 patients undergoing chronic haemodialysis treatment were
      reexamined after one year in order to assess changes in the anti-HVC antibody
      pattern in the intervening period, June 1992-June 1993. Using the ELISA II
      generation test, positive cases were found to have risen from 57 to 63 (from
      52.3% to 57.8%); the Riba II test showed 60 positive cases (previously 52) with 3
      undetermined (previously 5). The incidence of biochemical indicators of necrosis
      and/or cholestasis, negative in HCV patients, also presents a particular
      positivity (44%) in the presence of four antibody fractions. These data confirm
      the importance of serial determinations in anti-HCV antibody time, even if they
      do not correlate directly with the presence of the virus in the circulation and
      hence with its infecting capacity, the marker for which should be sought in the
      polymerase chain reaction.

PMID- 7570255
TI  - [Utility of electrophysiologic study using the blink reflex and brainstem evoked
      potentials for the evaluation of the course of uremic polyneuropathy].
AB  - On the present study the authors evaluate the utility of electrophysiologic
      examination in uraemic polyneuropathy. A group of 19 uraemic patients in chronic
      dialysis underwent the Blink reflex and BAEPSs study to evaluate the alterations
      of nervous pathways. The results obtained were compared with those of a group of
      10 healthy patients comparable for age and sex. The electrophysiologic parameters
      have been statistically compared with the plasma levels of vit. B12. folic acid,
      PTH and beta-2-microglobulin. The results show a significant difference of uremic
      patients compared with the healthy ones for the Blink reflex (ipsilateral and
      contralateral R2 responses). Also BAEPSs show significant alterations in the
      uraemic group (latencies of the III, V components). A statistically significantly
      inverse correlation is present between folic acid values and blink reflex R1 and
      R2 responses. Therefore our study shows the existence of a combined degeneration
      of central and peripheral nervous pathways in chronic uraemic patients. We
      believe that the decrease in folic acid concentration found in our study may be
      one of the causes of the beginning and then of the worsening of neurologic
      damage.

PMID- 7570256
TI  - [A computerized endurance test: efficacy of pelvic floor rehabilitation treatment
      in patients with stress incontinence].
AB  - In the present study the authors wanted to transfer rigorous methods of study,
      already in use in other sectors (sports, medicine, isokinetic work, etc.) of the
      validity of interventions made and their effectiveness, into an "emerging" field,
      that of perineal rehabilitation. 15 female patients, aged between 35 and 45,
      affected by stress incontinence underwent a baseline clinico-instrumental
      evaluation of the perineal floor including a computerized test of endurance. The
      patients then embarked upon a standardized rehabilitative perineal training
      lasting a month and at the end underwent an identical evaluation as that
      performed at the outset. Statistical analysis of the results obtained showed an
      objective improvement in the parameters considered (endovaginal pressure and its
      variations during a series of intermittent static contractions) quantitatively
      supporting clinical evidence.

PMID- 7570257
TI  - [Laser and ultrasonic therapy in simultaneous emission for the treatment of
      plastic penile induration].
AB  - Induratio penis plastica (IPP) or Peyronie's Disease is characterized by the
      presence of one or more fibrous patches in the tunica albuginea or intercavernous
      septum. IPP is a slowly evolving disease which may cause a bending of the penis
      as well as pain during erection. As an alternative to the numerous
      pharmacological therapies already existing, or in association with them, some
      kinds of physical treatments, such as ionophoresis, ultrasound therapy and laser
      therapy, have recently been used. In this study we have evaluated the
      effectiveness of physical therapy combined with laser and Ultrasounds in the
      treatment of IPP. Sixty-eight patients were randomly divided into three groups:
      the first group was treated with orgotein infiltrations, the second with laser
      and Ultrasounds and the third with an association of both treatments. On the
      basis of this study, we can affirm that the effectiveness of laser therapy
      associated with ultrasounds in treating painful symptomatology of IPP at its
      initial phase overlaps that of orgotein infiltrations. No measurable
      modifications were documented neither in patch dimensions nor in their
      echostructures and in no case remarkable modifications of the penile bending were
      evidenced. Therefore laser therapy associated with ultrasounds represents at the
      moment an efficacious alternative to medical treatment of IPP at the initial
      phase, as it does not present any kind of contraindications and it is surely
      better tolerated than any treatment with penile infiltrations.

PMID- 7570258
TI  - [Treatment of stage-I seminoma. Critical review].

PMID- 7570259
TI  - [Non-Hodgkin's lymphoma with primary localization in the bladder and prostate
      region. Description of a case].
AB  - The primary involvement of bladder and prostate by a non-Hodgkin lymphoma is
      extremely rare. Hematuria is the most common symptom in bladder lymphoma, outlet
      obstruction in prostate lymphoma. The histological diagnosis has to be confirmed
      by immunohistochemical methods. The treatment of choice is a combination of chemo
      and/or radiotherapy. With this report we present a case of non-Hodgkin lymphoma
      with primary involvement of bladder and prostate.

PMID- 7570262
TI  - [Echographic diagnosis of a large, asymptomatic, perirenal hematoma caused by a
      bleeding angiomyolipoma in tuberous sclerosis].
AB  - The authors describe a case of 21-year-old man suffering from tuberous sclerosis,
      more than once operated for subependymal astrocytomas, presenting multiple
      bilateral renal angiomyolipomas of 1.5 cm as greatest diameter. Last abdominal
      ultrasonographic exam, done a few years after the former, revealed an
      angiomyolipoma measuring 10 cm in diameter at the upper pole of the right kidney.
      This angiomyolipoma projected into a large haematoma of 15 cm in diameter,
      absolutely asymptomatic. After CT control bone lesions were removed. This case
      shows the progressive increase in number and size of renal angiomyolipomas, with
      subsequent haemorrhagic complications, suggesting as opportune periodic
      ultrasonographic controls.

PMID- 7570260
TI  - [Description of a case of squamous cell carcinoma of the renal pelvis].
AB  - A case of squamous cell carcinoma of renal pelvis is reported. A 73-year-old
      Caucasian male complained of macrohematuria. The echography and Computer
      Tomography scan of the abdomen and pelvis revealed a large tumor mass in the
      right kidney associated with lymphadenopathy. A nephrectomy of the right kidney
      and lymphadenectomy were performed. The isotologic examination revealed a
      squamous carcinoma of the renal pelvis involving the renal parenchyma and
      extending to the perirenal fat. The regional lymph nodes were also involved.
      Neoplastic invasion of inferior vena cava was found. Squamous carcinoma in situ
      and squamous metaplasia were noted in the urothelium adjacent to the tumor. Three
      months later an echography revealed a local recurrence of the disease. The
      patient underwent adjuvant chemotherapy. The aggressive course of the disease is
      in agreement with the poor prognosis of squamous carcinomas of the renal pelvis
      as previously reported in the literature.

PMID- 7570261
TI  - [Appearance in 2 brothers of double primary neoplasms: right renal carcinoma and
      gastric adenocarcinoma].
AB  - We report a clinical case of a double primitive tumour (right kidney clear cell
      carcinoma and gastric carcinoma) in two brothers. There is no history of cancer
      in the parents. Both patients were previously affected by gastric ulcer. No
      report of association between the two neoplasms was found in literature. The age
      of the patients (61 and 70 years) and the singleness of the kidney tumour seem to
      exclude the case of a familial kidney cancer. The neoplastic transformation of
      the gastric ulcer is instead a quite frequent report with an incidence of about
      1%. Alterations of oncogenes or tumour suppressor genes shared from both neoplasm
      are at present still unknown. Nevertheless molecular analysis of patients'
      neoplastic genome could point out typical chromosome translocations/deletions or
      gene mutations.

PMID- 7570265
TI  - [Autotransfusion: reality or Utopia?].

PMID- 7570264
TI  - [Measurement of skeletal alkaline phosphatase in prostatic carcinoma. Preliminary
      report].
AB  - Bone metastases frequently occur in prostate carcinoma. Total body radionuclide
      scan with diphosphonate methylene labelled with 99Tc is commonly used to diagnose
      such metastases. However this technique is aspecific and frequently unreliable.
      In recent years several biological markers dealing with bone metabolism were
      studied. Serum determination of skeletal alkaline phosphatase (ALP) and moreover
      of its bone isoenzyme (BAP) could be considered a reliable index of osteoblastic
      activity. In this preliminary report we analyzed a group of 43 patients affected
      by prostate carcinoma with or without bone metastases. The American Urological
      Association (AUA) staging system was adopted. Sixteen patients were D2, bone
      metastases had been suspected by means of radionuclide bone scan and confirmed by
      Computerized Tomography and/or aimed X-rays. Tandem R-Ostase by Hybritech was
      used to measure BAP, normal value is set to 20 micrograms/L. All D2 tumours had
      pathological BAP values (mean value 87.50 micrograms/l); 1/3 stage A, 5/13 stage
      B, 5/9 stage C and 0/2 stage D1 patients had pathological findings. One of this
      patients, stage C, revealed a bone metastase at a later bone scan.

PMID- 7570263
TI  - [A new method for treating benign prostatic hypertrophy: transurethral prostatic
      vaporization].

PMID- 7570267
TI  - [Hematology: a place for all].

PMID- 7570266
TI  - [Is there any clinical significance to anti-IgA antibodies which appear in
      patients with immunodeficiencies treated with intravenous gamma globulin?].

PMID- 7570268
TI  - [Immunohematologic study in 112 patients with myelodysplastic syndromes: 10-year
      analysis].
AB  - PURPOSE: To describe the immunohematological response after multiple red blood
      cells transfusions in 112 patients with myelodysplastic syndromes (MDS). PATIENTS
      AND METHODS: From 1982 to 1992 every patient with MDS entered the study.
      Immunohematological studies consisted of an antibody screening test (AST) and a
      direct antiglobulin test (DAT) at diagnosis and after every four transfused units
      of red blood cell concentrates. RESULTS: Twenty-three out of 112 patients (20.5%)
      presented a positive AST and/or DAT during the study period. Eleven out of the 23
      patients (9.8%) developed a positive DAT, six of them with red cell
      alloantibodies associated. In the remaining 12 patients (10.7%) the immune
      response observed was the development of red cell alloantibodies without a
      positive DAT. No patient presented with positive AST or DAT at diagnosis and no
      differences were observed in the pattern of immunohematological response and the
      FAB subtype. CONCLUSION: Patients with MDS have disordered immune systems with a
      high prevalence of autoantibodies against red cells. However, the incidence of
      red cell alloimmunization is similar to that observed in other multitransfused
      populations. Finally, despite the high immunization rate, the absence of any
      hemolytical reaction make the AST and DAT a safe and effective method of
      pretransfusion testing in this heavily transfused population.

PMID- 7570269
TI  - [Efficacy of various treatments in the management of idiopathic thrombocytopenic
      purpura in the adult].
AB  - PURPOSE: To evaluate the ITP treatment modalities and their results in a series
      of 30 adult patients. PATIENTS AND METHODS: 30 patients, age 15-74, were
      diagnosed of ITP in our institution between 1988 and December 1991. We defined
      the ITP as: mild (platelets > or = 50 x 10(9)/L and < or = 120 x 10(9)/L),
      moderate (platelets 25-50 x 10(9)/L) and severe (platelets < or = 25 x 10(9)/L).
      Treatment was initiated when the platelet count reached a level < 50 x 10(9)/L.
      Initial therapy was oral prednisone or methyl-prednisolone in all patients. In 12
      unresponsive patients the treatment included splenectomy. Patients who fail
      steroid therapy and splenectomy received additional lines of therapy, that
      included: vincristine (n = 2), vinblastine (n = 1), danazol (n = 5), anti D
      immunoglobulin (n = 6), methotrexate (n = 2), intravenous immunoglobulin (n = 3).
      RESULTS: Complete remission was obtained in 19 patients with a follow-up of 3 to
      55 months (median, 30 months). Partial remission was achieved in 4 patients, that
      was sustained for 9 to 39 months (median, 22.5 months) after initial therapy. One
      unresponsive patient died of infection. Six mild ITP patients did not require
      therapy with a follow-up of 14 to 56 months (median, 33.1 months). CONCLUSION: In
      adult patients with mild ITP, therapy is not required. Steroid therapy remains
      the initial therapeutic choice for moderate and severe ITP. In unresponsive
      patients useful alternative choices are splenectomy, danazol, anti D
      immunoglobulin and methotrexate.

PMID- 7570273
TI  - [Use of aprotinin in cardiovascular surgery].

PMID- 7570271
TI  - [Extramedullary toxicity in bone marrow transplantation using busulfan and
      cyclophosphamide conditioning].
AB  - PURPOSE: To evaluate the toxic extramedullary morbidity of the conditioning
      treatment with BuCy for BMT, as well as the usefulness of pentoxyphyllin (PTX)
      and methylprednisolone (MP) in the prophylaxis of mucositis. PATIENTS AND
      METHODS: Forty-eight patients with blood malignancies (AML, 19; ALL, 14;
      indifferentiated AL, 1; CML, 9; lymphoblastic lymphoma, 3; RAEB, 1; RAEBT, 1),
      subjected to BMT (16 autologous and 32 allo-BMT) were retrospectively revised.
      They all had been treated with BuCy as conditioning regimen. The GVHD prophylaxis
      was made in allo-BMT with cyclosporin and short-term methotrexate. Twelve
      patients received PTX-MP as mucositis prophylaxis. RESULTS: Some kind of toxicity
      was found in 47 of the 48 patients, mostly grade I-II (45 cases). The commonest
      sites involved were the mouth (87.5%) and the liver (30.23%). Neither veno
      occlusive liver disease nor pulmonary toxicity were present in any case. Heart
      toxicity was seen only in 2 cases, while 3 had haemorrhagic cystitis due to Cy.
      The severity of the mucositis was lesser in those patients receiving PTX-MP, so
      the requirements of NPT were lower in them (p = 0.02). CONCLUSIONS: The toxicity
      of the BuCy conditioning regimen was lesser than that of Cy+total body
      irradiation, with the same eradicating capability. Prophylaxis with PTX-MP could
      prove effective in reducing mucositis.

PMID- 7570270
TI  - [Hepatitis C virus in plasmapheresis donors].
AB  - The high prevalence of the hepatitis C virus (HCV) infection among plasmapheresis
      donors has been reported in several countries and Cuba. We have studied the
      possible relationship between the laboratory results and the real infectious
      state of the anti-HCV positive individuals, as well as the possible routes of
      infection in this population. MATERIALS AND METHODS: Retrospective data were
      analyzed and a prospective monthly serologic (anti-HCV) and biochemical (alanine
      aminotransferase) follow-up was established to 61 regular plasmapheresis donors,
      negative to hepatitis B markers, of a unit, which showed a prevalence of 48.3% of
      infection among these donors. RESULTS AND CONCLUSION: A direct correlation
      between the presence of antibodies to HCV and liver injury was found. No
      significant connection was observed between age, sex, race or sensitizing
      material with the positivity to anti-HCV, but it was significant with the time in
      plasma donation. Our results denote the risk of transmission of the HCV infection
      in the plasmapheresis units, pointing out the importance of the nosocomial route
      of infection.

PMID- 7570275
TI  - [Congenital deficiency of factor Xii and spontaenous venous thrombosis treated
      with urokinase].
AB  - There is a well known relationship between factor XII deficiency and arterial and
      venous thrombosis. A new case of moderate factor XII deficiency associated to
      spontaneous deep vein thrombosis and treated with Urokinase is reported. The
      patient had a partial response to the treatment with Urokinase, with normal study
      of the fibrinolytic system. The deficiency was found in five relatives within the
      three generations studied. The genetic transmission had an autosomic dominant
      pattern. We feel that there is no relationship between the family history or the
      degree of factor XII deficiency and the risk of developing deep venous
      thrombosis.

PMID- 7570274
TI  - [Electrolytic changes in children with acute lymphoblastic leukemia during
      remission induction].
AB  - The alterations of the water-electrolyte balance are among the commonest early
      complications of treatment in children with acute lymphoblastic leukaemia (ALL).
      A study was carried out in thirteen patients with ALL aged between 1.5 and 14
      years. Four had high risk ALL and nine had standard risk ALL. All patients
      received intravenous epirubicin and vincristine, per os prednisone, allopurinol
      and bicarbonate, and intrathecal methotrexate and hydrocortisone. Venous blood
      was drawn before starting therapy and on days second and sixth of treatment in
      order to assay sodium, potassium, calcium, phosphate, magnesium, albumin, urea
      nitrogen, creatinine and uric acid concentrations. The following alterations were
      found: hyponatraemia in 4 cases, hypokalemia in 9, hypomagnesaemia in 9,
      hypocalcaemia in 11, hypophosphataemia in 9, hypouricemia in 3 and hyperuricaemia
      in 3 others. None of the patients developed acute renal insufficiency. These
      abnormalities could be due to the leukaemia itself or appear as a consequence of
      the remission induction treatment.

PMID- 7570272
TI  - [Iron: perspective on the athletic woman].

PMID- 7570276
TI  - [Thrombocytopenia with absence of the radius in a 24-year-old woman].
AB  - Thrombocytopenia with absent radius syndrome (TAR) is a rare disorder appearing
      at birth or soon after. The heredity pattern is autosomal recessive, although
      some patients in successive generations have been reported. A 24 year-old woman
      is presented who had moderate thrombocytopenia and shortened forearms due to lack
      of radius, with preserved thumbs. Her peripheral blood was normal but for a
      decreased platelet count. The bone marrow megakaryocytes were decreased as well.
      No other relatives were affected. The association of thrombocytopenia and
      bilateral radius aplasia, along with the differential diagnosis, are commented,
      stress being laid on the fact that the patient was diagnosed in adulthood.

PMID- 7570277
TI  - [Hematology in crisis?].

PMID- 7570279
TI  - [Hematology and hemotherapy: quo vadis?].

PMID- 7570278
TI  - [The crisis in hematology].

PMID- 7570281
TI  - [The hematologist in the community hospital].

PMID- 7570280
TI  - [The general hematologist].

PMID- 7570284
TI  - [Hemoglobinopathies in the Bahia de Cadiz].

PMID- 7570283
TI  - [Evaluation of the Serono System 9020+ hematologic analyzer in oncohematologic
      patients].

PMID- 7570282
TI  - [Do we observe what we transfuse?].

PMID- 7570285
TI  - [Hemoglobin C in the 1st year of life].

PMID- 7570287
TI  - [Chronic neutrophilic leukemia (CNL) and meningeal tuberculosis (TBC): chance or
      cause?].

PMID- 7570286
TI  - [Pneumonia caused by Salmonella in a patient with myeloma].

PMID- 7570290
TI  - Alpha 4-integrin-dependent emigration of monocytes.

PMID- 7570292
TI  - VLA-4 and its ligands: relevance to kidney diseases.
AB  - Alterations in cellular immunity have been implicated in many kidney diseases.
      The role of the adhesion molecule VLA-4 and its known ligands VCAM-1 and CS-1
      have just begun to be evaluated in association with kidney diseases. VCAM-1 in
      human kidney is normally expressed in the Bowman's capsule, in the proximal renal
      tubule, and in the vascular endothelium. Up-regulation of VCAM-1 expression is
      seen in many different forms of glomerulonephritis as well as in a mouse model of
      lupus nephritis. Up-regulation of VCAM-1 expression is observed in the renal
      allograft with acute cellular rejection, and correlates with areas of leukocyte
      infiltration and vascular inflammation. CS-1 may also be up-regulated in the
      rejecting kidney. Animal studies on cardiac transplantation demonstrate that
      blockade of VLA-4 or VCAM-1 can attenuate transplant rejection. Hemodialysis
      patients, known to have a cellular immunodeficiency, have increased levels of
      soluble VCAM-1 in their serum. There is increasing evidence that there are
      alterations in VLA-4, VCAM-1 and CS-1 in association with kidney diseases.
      Further studies will be required to delineate the role of these molecules in the
      immunopathogenesis of select kidney diseases and the possibility of intervening
      in these adhesion pathways to ameliorate clinical syndromes.

PMID- 7570289
TI  - Pathophysiological aspects of VLA-4 interactions and possibilities for
      therapeutical interventions.

PMID- 7570291
TI  - Alpha 4 integrin-induced cytokine production and eosinophil function.

PMID- 7570288
TI  - The adhesion cascade and anti-adhesion therapy: an overview.

PMID- 7570293
TI  - Anti-integrin immunotherapy in rheumatoid arthritis: protective effect of anti
      alpha 4 antibody in adjuvant arthritis.

PMID- 7570294
TI  - Treatment of delayed-type hypersensitivity with inhibitors of the VLA-4 integrin.

PMID- 7570297
TI  - [On our own account: the impact factor].

PMID- 7570298
TI  - [Radiogenic lung reactions. Pathogenesis--prevention--therapy].
AB  - PURPOSE: The lung is the dose-limiting structure within the thorax. Radiation
      induced lung damage resulting in either pneumonitis or pulmonary fibrosis limits
      the total dose of radiotherapy in the thoracic region. The paper reviewed and
      discussed the current knowledge of radiogenic pneumopathy. PATIENTS AND METHODS:
      Analysis was done of experimental results and published data concerning lung
      reaction after radiotherapy. RESULTS: From a clinical point of view the radiation
      induced lung damage can be described by 2 distinct phases: pneumonitis (4 to 6
      weeks post radiationem) and pulmonary fibrosis (1 to 2 years post radiationem).
      Although there is increasing additional information on the etiology of radiation
      induced lung damage up to now effective treatment based on these knowledges is
      available. The frequency of radiogenic pneumopathy detected by X-ray
      investigation after a radiation treatment demonstrates great difference between
      several investigators which is mainly caused by differences in the sequence of X
      ray investigation. The ED50-value of pneumonitis after a conventional
      fractionated radiotherapy is about 35 Gy. CONCLUSION: Minimizing the frequency of
      radiation-induced lung injury it ist necessary to check prior to radiotherapy the
      treatment ability of a patient concerning its lung function conditions, to remain
      a great untreated lung volume in treatment planning, to use smaller doses per
      fraction in the irradiated parts of the lung and to calculate the dose
      distribution with the individual values of lung density of the patient. In cases
      of occurring pneumopathy with clinical signs only symptomatic treatment is
      possible.

PMID- 7570296
TI  - Therapeutic approaches to asthma based on VLA-4 integrin and its counter
      receptors.

PMID- 7570299
TI  - [Stereotaxic convergent irradiation with the gamma knife. A study of the
      possibilities for optimizing the dosage distribution].
AB  - PURPOSE: On April 1992, the first stereotactic radiosurgical procedure using the
      gamma knife was performed at the University Medical School Graz, Department of
      Neurosurgery. Accurate dose optimization is the foundation of a convenient and
      responsible utilization of this modality. But there are limits, because the final
      collimation is only achieved by 1 of the 4 special helm collimators. MATERIAL AND
      METHODS: The possibilities of dose optimization and its influence on the dose
      distributions were investigated and partly compared with results of film
      densitometry measurements. In detail, the technique, which uses the same
      isocenter, but different sized collimators was studied. The influence of these
      optimization techniques on the resulting dose distributions and the dose gradient
      at the edge of the treatment planning volume was analyzed. Also the visions for
      an effective dose optimization are discussed. RESULTS: With 2 shots of different
      diameters, located at the same target coordinates and different weighting of time
      any collimator size between the 4 mm and 18 mm can be achieved. Because of that,
      a combination of more than 2 collimators is not meaningful. With the combined
      shots the dose fall gradient was less than that of either of the single shots
      involved in the combination. CONCLUSIONS: With the available physical and
      technical possibilities only a limited, very time consuming optimization is
      practicable. The quality control of isodose distributions requires optimizations
      in hard- and software, that enable CT- or MRT-based 3-dimensional visualization
      and dose volume analysis.

PMID- 7570301
TI  - Radiogenic responses of normal cells induced by fractionated irradiation--a
      simulation study. Part II. Late responses.
AB  - AIM: Based on controlled theory, a computed simulation model has been constructed
      which describes the time course of slowly responding normal cells after
      irradiation exposure. Subsequently, different clinical irradiation schemes are
      compared in regard to their delayed radiogenic responses referred to as late
      effects in radiological terminology. METHOD: A cybernetic model of a parenchymal
      tissue consisting of dominantly resting functional cells has been developed and
      transferred into a computer model. The radiation effects are considered by
      characteristic cell parameters as well as by the linear-quadratic model. RESULTS:
      Three kinds of tissue (brain and lung parenchyma of the mouse, liver parenchyma
      of rat) have been irradiated in the model according to standard-, super-,
      hyperfractionation and a single high dose per week. The simulation studies
      indicate that the late reaction of brain parenchyma to hyperfractionation (3 x
      1.5 Gy per day) and of lung parenchyma tissue with regard to all fractionation
      schemes applied is particularly severe. In contrast to these observations the
      behavior of liver parenchyma is not unique: If Dtotal amounts to 60 Gy there is
      no evidence for compensation of radiation damages, but if Dtotal is restricted to
      30 Gy the corresponding evidence can be expected for all schemes. In the case of
      a high single dose of 6 Gy a reduction of the recovery time from 1 week to 2...2
      days yields also an indication of a severe damage, even if Dtotal amounts only to
      30 Gy. CONCLUSIONS: A comparison of the simulation results basing to the survival
      of cell numbers with clinical experience and practice shows that the clinical
      reality can qualitatively be represented by the model. This opens the door for
      connecting side effects to normal tissue with the corresponding tumor efficacy
      (discussed in previous papers). The model is open to further refinement and to
      discussions referring to the phenomenon of late effects.

PMID- 7570300
TI  - [The use of an early postoperative interstitial-hyperthermia combination therapy
      in malignant gliomas].
AB  - BACKGROUND: The survival of people suffering from malignant gliomas (WHO level
      III and IV) is predominantly limited by local progress in the primary tumor
      region. Interstitial hyperthermia combined with radiotherapy or chemotherapy is
      one approach for the intensification of local therapy. It is possible to combine
      (partial) tumor resection with hyperthermia as well as with brachytherapy by
      implanting catheters intraoperatively. PATIENTS AND METHODS: A pilot study was
      performed to examine practicality, tolerability, effectiveness and scope for
      improvement in early postoperative hyperthermia treatment following catheter
      implantation as part of (partial) tumor resection. Each CT data set was
      transferred into a VAX 3100 workstation for retrospective analysis of the
      hyperthermia treatment. The implanted catheters were segmented and the
      distributions of power density and temperature were simulated. We sought to
      achieve the best possible temperature distributions by optimising the catheter
      arrangement in the planning calculations. The corresponding Ir-192-source
      brachytherapy treatments were simulated in a similar way using the implanted, as
      well as optimised catheter arrays. RESULTS: Intraoperative catheter implantation
      in 4 patients was problem-free. Postoperative complications were not observed,
      neither were infections. Interstitial microwave hyperthermia in combination with
      percutaneous irradiation or chemotherapy a few days after the operation was also
      tolerated well by all patients. Effective temperatures (of at least 42 degrees C)
      were regularly achieved at measurement points, but the temperature distributions
      were unsatisfactory, with T90 values (the temperature reached in at least 90% of
      the target volume) of under 38 degrees C. Measured temperature/position curves
      showed qualitative correlation with the simulated calculations. The catheter
      positions determined by optimisation varied significantly from the positions
      clinically used. CONCLUSIONS: Early postoperative combination therapy using
      hyperthermia for the treatment of malignant gliomas is a very practical approach.
      The optimisation strategies described should be used preoperatively to plan
      catheter arrays for interstitial hyperthermia and brachytherapy, and these arrays
      should be implanted using stereotaxic surgery.

PMID- 7570302
TI  - [The effect of x-rays on experimental arthritis in the rat].
AB  - AIMS: We investigated the therapeutic efficacy of low doses of X-rays on
      different in-vivo models of monoarticular arthritis which have been developed for
      the investigation of anti-inflammatory drugs. MATERIAL AND METHODS: Zymosan or
      heat-inactivated mycobacterium tuberculosis was injected into 1 knee joint of
      Wistar rats to produce, via different pathogenetic mechanisms, an acute
      monoarticular arthritis. Five days later, the amount of joint swelling, bone
      destruction and cartilage catabolism were measured. Immediately after arthritis
      induction, the knees were irradiated with a single dose of 5 Gy or with 4 daily
      fractions of 1 Gy. RESULTS: X-irradiation with daily doses of 1 Gy significantly
      reduced bone loss and cartilage degradation in Zymosan-induced arthritis and
      joint swelling in mycobacterium tuberculosis induced arthritis. However, a single
      high radiation dose significantly increased bone loss in mycobacterium
      tuberculosis induced arthritis. CONCLUSIONS: These data confirm the hypothesis of
      an anti-inflammatory effect of low radiation doses which so far has been based
      only on clinical experience. By using an established model of monoarticular
      arthritis we have now the opportunity to study the mechanism of the anti
      inflammatory radiation effect in comparison to that of anti-inflammatory drugs.
      This way, we hope to provide a scientific basis for the use of radiotherapy in
      various painful degenerative joint disorders.

PMID- 7570303
TI  - [Choroid metastasis in a patient with adenocarcinoma of the cervix. A case
      report].
AB  - PURPOSE: Choroidal metastasis from other primaries than breast cancer or lung
      cancer is a rare event. There is no documented case in the literature of a
      choroid metastasis in a patient with adenocarcinoma of the uterine cervix.
      PATIENT AND METHOD: The case of a pregnant 25-year-old woman with cervix
      carcinoma (stage FIGO Ib) is presented. Following abortion and radical surgery no
      additional treatment was performed. Two years later the patient developed the
      signs of retinal detachment and a partial visus lost in her left eye. A solitary
      choroidal metastasis in the left eye was diagnosed by an ophthalmologist. The
      additional CT of the lung showed pulmonary metastases. Histological examination
      of a biopsy revealed lung metastases from the cervix carcinoma. RESULTS: The
      choroid was irradiated up to a total dose of 40 Gy, 5 times a week with a single
      dose of 2 Gy. Then an additional chemotherapy was performed. Within the time of
      radiotherapy a relief of the symptom was obtained. Eight weeks after the end of
      radiotherapy there was no detectable tumor any more in the left eye (complete
      remission). CONCLUSIONS: The case illustrates the importance of rapidly
      responding to ophthalmologic complications in patients with cancer in general.
      Radiotherapy is a very effective treatment in reducing ophthalmologic symptoms in
      the case of choroidal metastases.

PMID- 7570304
TI  - [Is protein p53 an independent prognostic factor in bladder carcinoma?].

PMID- 7570307
TI  - [The size relationship of the invasive components to axillary lymph node status
      in primary breast carcinoma].

PMID- 7570306
TI  - [Prophylactic whole-brain irradiation (PCI) in patients with small-cell bronchial
      carcinoma (SCLC) in complete remission].

PMID- 7570308
TI  - Presidential address: More with less.

PMID- 7570295
TI  - VLA-4 and lymphocyte trafficking in immune-inflammatory states: novel therapeutic
      approaches in allograft arteriopathy.

PMID- 7570309
TI  - Benign biliary strictures: repair and outcome with a contemporary approach.
AB  - BACKGROUND: The Hepp-Couinaud technique is an innovative approach for repair of
      proximal biliary strictures. We have used this method selectively for bile duct
      reconstruction since 1982. Our aim was to analyze our experience with the
      surgical repair of benign biliary strictures in the decade since the Hepp
      Couinaud technique has become an integral component of our surgical management
      strategy. METHODS: Seventy-two patients undergoing surgical repair of benign
      biliary stricture between 1983 and 1992 were reviewed retrospectively. A grading
      system on clinical symptoms, results of liver function studies, and need for
      reintervention was used to assess outcome. RESULTS: For the 27 patients with
      noniatrogenic strictures, followed up a mean of 3.9 years, excellent or good
      results (grade A or B) were obtained in 88.9%. For the 45 patients with
      iatrogenic strictures, followed up a mean of 4.6 years, 86.7% were categorized as
      grade A or B. The cumulative probability of anastomotic failure was significantly
      less for the 21 patients in whom the Hepp-Couinaud method was used when compared
      with the 24 patients in whom it was not (p = 0.032). Outcome was not influenced
      by age, time delay from injury to reconstruction, preoperative stenting, the
      number of previous repairs, or the duration of postoperative stenting.
      CONCLUSIONS: Surgical reconstruction affords excellent or good results for the
      vast majority of patients with benign biliary strictures. For proximal iatrogenic
      strictures superior anastomotic durability is achieved with the Hepp-Couinaud
      technique.

PMID- 7570305
TI  - [Iliac crest aspiration in the assessment of bone marrow involvement in small
      cell bronchial carcinoma is sufficient].

PMID- 7570310
TI  - Malignancy, mortality, and medicosurgical management of Clostridium septicum
      infection.
AB  - BACKGROUND: Necrotizing Clostridium septicum infections (CSI) have a strong
      association with malignancy or immunosuppression. To clarify this relationship
      and determine how it impacted mortality, the experience with CSI at a single
      institution was reviewed. METHODS: Records of all patients admitted to our
      hospital with culture proven clostridial infection from 1966 through 1993 were
      reviewed. RESULTS: Among patients presenting with clinical gas gangrene, 281 had
      culture proven clostridial infection and 32 (11.4%) had CSI. The mortality among
      CSI patients was 56%, whereas 26% of all patients with clostridial infections
      died (p = 0.001). An associated malignancy was found in 50% of patients with CSI,
      whereas this was seen in only 11% of patients with other clostridial infections
      (p = 0.0001 for CSI versus clostridial infection overall). The remaining patients
      with spontaneous CSI all had evidence of immunosuppression. CONCLUSIONS: The high
      mortality and likelihood of associated malignancy or hematologic disease
      underscore the importance of a high index of suspicion and the need to search for
      and treat associated conditions in all patients with CSI.

PMID- 7570311
TI  - Comparison of the costs associated with medical and surgical treatment of
      obesity.
AB  - BACKGROUND: We compared the long-term costs and outcomes of gastric bypass versus
      medical therapy (very low-calorie diet plus weekly behavioral modification) for
      obese patients. METHODS: A successful outcome was defined as the loss of at least
      one third of excess weight that was maintained for the duration of the study. A
      minimal cost was assigned: $3000 for medical and $24,000 for surgical treatment.
      A cost per pound of weight lost for all patients successfully monitored was
      calculated. The Federal Trade Commission recently asked all weight loss programs
      to report this cost for patients at least 2 years after therapy. RESULTS: A total
      of 201 patients entered surgical and 161 entered medical therapy. The surgical
      group was initially heavier (mean body mass index [kg/m2] +/- SE = 49.3 +/- 0.6
      versus 41.2 +/- 0.7, p < 0.01), but each group's lowest mean body mass index was
      similar (31.8 versus 32.1, respectively). A significantly higher percentage of
      patients in the surgical versus the medical group were still successful at year
      5: 89% versus 21%. The cost per pound lost for medical therapy exceeded the cost
      of surgical therapy in the sixth posttreatment year (both more than $250/pound).
      CONCLUSIONS: Surgical treatment appears to be more cost-effective at producing
      and maintaining weight loss. It is imperative that long-term follow-up studies be
      funded to definitely establish this finding.

PMID- 7570312
TI  - Long-term follow-up of the Palmaz stent for iliac occlusive disease.
AB  - BACKGROUND: Thirty-eight limbs with iliac occlusive disease were treated with
      Palmaz stents from 1987 through 1991. METHODS: Indications for stent utilization
      included dissection induced by percutaneous transluminal balloon angioplasty
      (PTA) (10), restenosis after PTA (nine), post-PTA residual stenosis (nine),
      multiple stenoses or occlusion (five), and unfavorable location (five). RESULTS:
      The ankle/brachial pressure index increased from 0.53 +/- 0.27 to 0.8 +/- 0.26
      after stent deployment. The intraluminal pressure gradient decreased from 31.9 +/
      16.3 to 0.9 +/- 2.2 mm Hg after stent deployment. Complications included
      pseudoaneurysm (one), arteriovenous fistula (one), iliac perforation (one), groin
      hematoma (two), and occlusion (two). Follow-up arteriogram showed stenosis
      proximal or distal (n = 4) or within the stents (n = 4). These were treated with
      PTA or stents. Two patients required an aortobifemoral graft. Nine patients have
      died. Life table analysis showed a 1-, 3-, and 5-year primary and secondary
      cumulative patency of 87% +/- 5.9%, 74% +/- 8.2%, and 63% +/- 10% and 91% +/-
      5.1%, 91% +/- 5.6%, and 86% +/- 7.6%, respectively. CONCLUSIONS: Palmaz stents,
      often required to salvage a PTA failure, appear to maintain overall patency at a
      high level. However, intimal hyperplasia and the progression of atherosclerotic
      disease may result in a need for additional procedures to obtain this favorable
      outcome.

PMID- 7570315
TI  - Laparoscopic cholecystectomy during pregnancy.
AB  - BACKGROUND: Cholecystectomy represents the second most common nonobstetric
      operation during pregnancy. Published guidelines for laparoscopic cholecystectomy
      (LC) have considered it to be contraindicated in the gravid patient. Several
      cases of successful LCs in the gravid patient have been reported recently. This
      study reviews LC during pregnancy in my series and compares this experience with
      the published literature. METHODS: Five LCs were performed during pregnancy out
      of 380 cases between May 1990 and November 1994. Forty-one cases were retrieved
      via MEDLINE search. RESULTS: Three patients were in their second trimester (14,
      17, and 22 weeks), and two patients were in the third trimester (27.5 and 28
      weeks) in my series. The open technique was used in one patient. Intraoperative
      cholangiography was not performed. No maternal or fetal morbidity occurred. Forty
      one cases have been reported in the literature. Four patients were operated on
      during the first trimester, 35 during the second trimester, and two during the
      third trimester (range, 3 to 31 weeks) without fetal loss or maternal morbidity.
      Cholangiography was performed in 15 cases. Tocolytic agents were used in five of
      46 patients. CONCLUSIONS: Although additional clinical data are required,
      laparoscopic cholecystectomy is safe during pregnancy when undertaken by the
      skilled laparoscopic surgeon.

PMID- 7570314
TI  - Patient selection for breast conservation therapy with magnification mammography.
AB  - BACKGROUND: Breast-conserving therapy (BCT) is an appropriate treatment for women
      with breast carcinoma of limited extent. This study was undertaken to determine
      the ability of microfocal spot magnification mammography to identify women with
      multifocal or multicentric breast carcinoma who were unlikely to have all gross
      carcinoma removed with a limited breast resection. METHODS: Two hundred sixty
      three women with mammographically visible ductal carcinoma in situ and stage 1
      and 2 carcinoma who were clinical candidates for BCT were evaluated with
      magnification mammography before undergoing definitive local therapy. Biopsy
      specimens of additional abnormalities thought to have a greater than 2% risk of
      malignancy were obtained. RESULTS: Forty-seven women had other abnormalities in
      the index breast requiring intervention, and 216 had only the primary tumor
      identified. Mean age, cancer presentation, disease stage, and histologic tumor
      type did not differ between groups. BCT was successful in 97.2% of women without
      mammographic abnormalities versus 38% of women with abnormalities (p = 0.001).
      Clinical characteristics did not differ between patients undergoing successful
      BCT and those requiring mastectomy. Synchronous contralateral carcinoma was
      identified in 2.4% of women at risk. CONCLUSIONS: Magnification mammography
      allows accurate preoperative identification of patients requiring mastectomy or
      quadrantectomy and should be performed before diagnostic biopsy is done.

PMID- 7570313
TI  - Relationships between sclerosing cholangitis, inflammatory bowel disease, and
      cancer in patients undergoing liver transplantation.
AB  - BACKGROUND: Liver transplantation has emerged as the definitive treatment for
      primary sclerosing cholangitis (PSC). Its relationships to inflammatory bowel
      disease and cholangiocarcinoma were evaluated in this series. METHODS: Fifty
      three liver transplantations were performed in 41 patients with PSC at the
      University of Wisconsin from 1986 through 1994. Fourteen of the patients
      underwent colectomies for inflammatory bowel disease, eight before
      transplantation and six after transplantation. Five patients had
      cholangiocarcinoma on the hepatectomy specimen, and another two had been
      diagnosed before transplantation. RESULTS: Patient survival for PSC without
      cholangiocarcinoma was 85% and 62% at 2 and 9 years, respectively. No patient
      with PSC and cholangiocarcinoma has survived 2 years, although two patients were
      free of disease 11 and 20 months after transplantation. Despite maintenance
      immunosuppression seven patients with liver transplants had reactivation of
      inflammatory bowel disease and colon carcinoma developed in three after liver
      transplantation. CONCLUSIONS: Liver transplantation should be performed early in
      the course of PSC to avoid the lethal complications of cholangiocarcinoma.
      Careful colonoscopic follow-up is necessary in patients undergoing
      transplantation for PSC because immunosuppressive therapy does not necessarily
      cause inflammatory bowel disease to be quiescent, nor does it reduce the risk of
      colon carcinoma developing.

PMID- 7570317
TI  - Arguments against routine contralateral mastectomy or undirected biopsy for
      invasive lobular breast cancer.
AB  - BACKGROUND: Management of the contralateral normal-appearing breast in a patient
      with ipsilateral invasive lobular carcinoma (ILC) is controversial. METHODS: The
      case histories of patients with histologically proven ILC who underwent
      definitive surgery at our institution from 1978 to 1991 were retrospectively
      reviewed. RESULTS: Of the 419 women with ILC, 36 (8.6%) had bilateral cancer,
      with a cumulative risk of 10% at 10 years. Twenty-five (69%) of these cancers
      were suspected before operation. From 105 contralateral prophylactic surgical
      procedures, seven (64%) in-situ and four (36%) invasive cancers were detected.
      The age at presentation and multifocality of the index cancer were significantly
      different between patients with unilateral and those with bilateral cancers. No
      survival difference was noted between patients whose contralateral cancers were
      suspected clinically and those whose cancers were detected prophylactically.
      Survival rates between patients with unilateral versus bilateral cancers were
      also not different. However, patients with contralateral prophylactic surgery had
      a better prognosis than those with unilateral tumors and no prophylaxis.
      CONCLUSIONS: Ten percent of patients with ILC experienced bilateral cancers
      during a period of 10 years. Survival was not influenced by the development of a
      second cancer, but it improved with surgical prophylaxis.

PMID- 7570316
TI  - Radioimmunoguided Surgery system improves survival for patients with recurrent
      colorectal cancer.
AB  - BACKGROUND: Advanced colorectal cancer is fatal. No systemic therapies have
      resulted in increased patient survival. METHODS: One hundred thirty-one patients
      with recurrent colorectal cancer enrolled in two prospective nonrandomized
      studies using Radioimmunoguided Surgery (RIGS) system from May 1986 to April 1992
      have been analyzed. Eighty-six patients were injected with the anti-tumor
      associated glycoprotein (TAG) antibody B72.3, and 45 patients were injected with
      the second-generation anti-TAG monoclonal antibody CC49. Both monoclonal
      antibodies were radiolabeled with iodine 125. Both traditional and RIGS
      explorations were used to determine resectability. Follow-up was a minimum of 28
      months. RESULTS: Forty-nine (37.4%) of the 131 patients underwent a curative
      resection. Twenty-seven of the patients (55%) are alive 2 to 8 years after
      operation. The cancers of the remaining 82 patients were unresectable, and only
      two patients (2%) are alive. In this unresectable group alternative
      intraoperative therapeutic methods (intraoperative radiation therapy,
      intraperitoneal hyperthermic perfusion, hepatic lines, and brachytherapy) were
      tried in 11 patients with two survivors. There were no survivors in 18 patients
      whose cancers were found to be traditionally resectable but unresectable with
      RIGS or in the 53 patients whose cancers were clearly unresectable by traditional
      exploration. Patients selected for curative resection had significantly increased
      survival (p < 0.0001). CONCLUSIONS: As an intraoperative tool RIGS significantly
      improves the selection of patients for curative resection.

PMID- 7570318
TI  - Incidental Meckel's diverticulectomy in adults.
AB  - BACKGROUND: Incidental Meckel's diverticulectomy has been advocated by some
      surgeons because of the lower associated morbidity and mortality in this setting
      than when resection is indicated. Others have argued that the low risk of
      complication occurrence does not justify prophylactic removal. The issue remains
      controversial. METHODS: Medical records of all adults undergoing Meckel's
      diverticulectomy at four acute care hospitals during the 5-year period 1989
      through 1993 were retrospectively reviewed. Decision analysis was used to
      determine relative risks for incidental resection compared to indicated resection
      for a complication. RESULTS: Ninety patients underwent incidental
      diverticulectomy. Morbidity was 2% and mortality 0%. Four patients underwent
      resection for a complication of their diverticulum. Morbidity and mortality were
      each 0%. Combining these results with previously reported results and using
      decision analysis, the conditional probabilities of producing surgical morbidity
      or mortality in the adult population at risk by only resecting symptomatic
      diverticula are 0.2% and 0.04%, respectively. The comparable risks for resecting
      all incidentally discovered diverticula are 4.6% and 0.2%. CONCLUSIONS:
      Incidental diverticulectomy in adults should be abandoned.

PMID- 7570319
TI  - Epithelioid gastric stromal tumors (leiomyoblastomas): a study of fifty-five
      cases.
AB  - BACKGROUND: Epithelioid gastric stromal tumors form a distinct histologic subset
      of gastric tumors whose malignant potential and prognosis are controversial.
      METHODS: Fifty-five patients with epithelioid gastric stromal tumors accounted
      for 11.5% of patients undergoing definitive operations for gastric stromal tumors
      from 1960 to 1986. Medical records and pathology slides were reviewed, and
      immunohistochemical staining and flow cytometry were performed. The Kaplan-Meier
      method was used to estimate survival. Survival curves were compared with log-rank
      tests and Cox proportional hazards model. RESULTS: Of the 55 tumors, 40 were
      benign and 15 (27%) were malignant. Mean follow-up was 10.5 years. Ten patients
      died of their disease. No patient with a benign tumor had recurrence of
      metastasis, but all patients with high-grade malignancy had died of disease
      within 3 years after diagnosis. Seventy-five percent of proximal tumors were
      malignant. Extent of resection had no impact on survival (p = 0.5). CONCLUSIONS:
      The best determinant of tumor behavior was histologic grade. Twenty-seven percent
      of patients had malignant tumors, and 67% of these died of disease. Other
      significant prognostic factors included a mitotic count greater than 5/10 high
      power fields, size larger than 6 cm, aneuploidy, and higher S-phase fraction (p <
      0.01). Proximal lesions were more likely to be malignant. Extent of surgical
      treatment had no effect on survival.

PMID- 7570320
TI  - Evolution of the surgical approach for replacement of degenerated mitral
      bioprostheses.
AB  - BACKGROUND: Primary tissue failure is the most frequent indication for
      reoperation in patients with a mitral bioprosthetic valve (MBPV). Complete
      excision of the bioprosthesis is time-consuming and may be complicated by cardiac
      rupture at the atrioventricular junction or the posterior left ventricular wall
      where a strut is embedded, injury to the circumflex coronary artery, or late
      perivalvular leak. A new approach to avoid these complications by excision of
      only the bioprosthetic tissue and attachment of a St. Jude valve (SJV) to the
      intact stent has been developed and evaluated. METHODS: The results of
      replacement of failed MBPV with SJV in 71 consecutive patients between September
      1992 and December 1994 were analyzed; 57 patients had the valve replaced after
      complete excision and 14 with stent preservation. The demographic and clinical
      profiles of the two groups were similar. RESULTS: Among patients undergoing
      complete excision of the MBPV, operative mortality was 14% (8 of 57), with 12
      late deaths and a 5-year survival of 75% and three late perivalvular dehiscences
      requiring another operation. No operative deaths occurred in the intact stent
      group and one late death (cancer), and all the remaining patients are doing well
      without perivalvular leaks or other complications. CONCLUSIONS: Leaving the MBPV
      stent intact eliminates the need for extensive dissection, thus shortening and
      simplifying the procedure and diminishing its attendant mortality and morbidity.
      It offers a safe and logical approach to replacement of a degenerated MBPV with a
      SJV of comparable size.

PMID- 7570321
TI  - Beta 1 integrin expression in malignant melanoma predicts occult lymph node
      metastases.
AB  - BACKGROUND: Elective lymph node dissection for malignant melanoma is still
      controversial. Experimental studies suggest that differential expression,
      activation, or both of beta1 integrins facilitate melanoma metastases. However,
      the clinical significance of beta1 integrin expression in human melanoma is
      unclear. METHODS: We examined primary cutaneous melanomas from 76 patients
      undergoing elective lymph mode dissection. We quantified the percentage of tumor
      area stained by beta1 integrin antibody with an image analyzer. RESULTS: beta1
      integrin was expressed in all 23 primary tumors from patients with pathologically
      positive lymph nodes (LNs) but in only 14 (26%) of 53 cases with pathologically
      negative nodes (p < 0.001). No patients with beta1 integrin-negative tumors had
      LN involvement, whereas 23 (62%) of 37 patients with beta1 integrin-positive
      tumors had LN metastases (p < 0.001). Furthermore, 21 (91%) of 23 cases with LN
      metastases but only 4 (8%) of 53 cases without had beta1 integrin staining of 10%
      or more of tumor area (p < 0.001). CONCLUSIONS: Our study is the first to show a
      correlation between expression of a molecular marker in the primary cutaneous
      melanoma and likelihood of regional LN metastases. beta1 immunostaining of 10% or
      more of tumor area reliably predicts patients most likely to harbor occult LN
      metastases and likely to benefit from ELND.

PMID- 7570322
TI  - Diagnosing the indeterminate pulmonary nodule: percutaneous biopsy versus
      thoracoscopy.
AB  - BACKGROUND: The malignant potential of indeterminate solitary pulmonary nodules
      (SPN) mandates accurate diagnostic management. METHODS: 613 patients undergoing
      either computed tomographic lung biopsy (CT-Bx) (n = 312) or thoracoscopic
      excisional biopsy (Thor-Bx) (n = 301) for the diagnosis of SPN were evaluated for
      relative accuracy, complications, and effect on clinical treatment. RESULTS: CT
      Bx identified a malignant diagnosis (Dx) in 201 (64%) of 312 patients; 85 (42%)
      underwent operations. A total of 116 patients (58%) with synchronous cancer (n =
      16), impaired physiologic condition, or unresectable lesions (n = 100) were not
      operated. Surgical treatment was deferred for 20 patients (6%) with a "specific
      benign" Dx and 44 physiologically impaired patients with "nonspecific benign" CT
      Bx. Forty-seven patients with "nonspecific benign" Dx underwent operation. Thirty
      two (68%) lesions were malignant (4 metastatic, 28 primary cancer). CT-Bx
      accuracy was 86% for malignant and 79 (71%) of 111) for benign lesions. Surgery
      was still required for 132 (82%) of 163 patients with resectable lesions.
      Complications occurred in 24% of patients. A specific benign or malignant Dx was
      obtained in 292 (96%) of 301 patients undergoing Thor-Bx. Conversion to
      thoracotomy for lobectomy occurred in 38 (21%) of 179 patients with lung cancer.
      One hundred forty-one patients with lung cancer and impaired physiologic
      condition and all patients with metastatic (n = 44) and benign lesions (n = 78)
      had thoracoscopic resection alone. Complications occurred in 22% of patients.
      CONCLUSIONS: Limited accuracy for benign Dx with CT-Bx requires surgical biopsy
      for patients with SPN with adequate physiologic reserve. Thor-Bx is a safe and
      accurate minimally invasive surgical approach to resectable peripheral SPN.

PMID- 7570323
TI  - Magnetic resonance imaging-derived parameter of portal flow predicts volume
      mediated pulmonary hypertension in liver transplantation candidates.
AB  - BACKGROUND: Pulmonary hypertension is a source of perioperative mortality after
      orthotopic liver transplantation (OLT). The purpose of this study is to (1)
      characterize the pulmonary hemodynamic response in OLT candidates, and (2)
      determine whether portal flow index (PFI), a magnetic resonance imaging (MRI)
      derived parameter, is a useful predictor of the pulmonary hemodynamic response.
      METHODS: Twenty-five consecutive OLT candidates underwent right heart
      catheterization with pressure measurements at baseline and after infusion of 1 L
      of crystalloid. MRI, chest roentgenography, electrocardiography, and
      echocardiography were also performed as routine screening techniques. Sixteen
      patients in intensive care unit with normal liver function served as controls.
      RESULTS: After volume infusion, pulmonary hypertension (mean pulmonary artery
      pressure greater than 25 mm Hg) developed in 9 of 25 OLT candidates with
      elevations in both pulmonary capillary wedge and mean pulmonary pressures. In
      contrast, 0 of 16 controls experienced pulmonary hypertension (p < 0.01).
      Although routine modalities did not predict this hemodynamic response, PFI had a
      94% specificity and 78% sensitivity. CONCLUSIONS: OLT candidates exhibit volume
      induced pulmonary hypertension with responses suggestive of left ventricular
      dysfunction. The significance of this observation is unknown, but the MRI-derived
      parameter, PFI, may serve as a screening technique to limit catheterization to a
      select group of OLT candidates.

PMID- 7570324
TI  - Results of a change to routine fluorocholangiography during laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Early in our experience with laparoscopic cholecystectomy (LC),
      intraoperative cholangiography (IOC) was performed selectively with static
      imaging techniques. We subsequently changed to routine digital
      fluorocholangiography (FIOC) and evaluated the results of this strategy. METHODS:
      In a consecutive series of 356 LCs, 11 patients (3%) were converted to open
      cholecystectomy. In the remaining 345 patients FIOC was attempted in 336 patients
      (97%) and was successfully completed in 328 patients (95%). Results of IOC and
      outcomes were compared prospectively in patients without indications for IOC
      (group I, n = 185) with those with criteria for selective IOC (group 2, n = 160)
      and retrospectively with patients without indications for IOC undergoing static
      IOC (group 3, n = 56). RESULTS: Time to perform FIOC was less than for static IOC
      (14 +/- 1 versus 24 +/- 1 minutes, p < 0.001). Aberrant ductal anatomy was
      appreciated by using FIOC in 11% but affected operative management in only 3% of
      patients. Choledocholithiasis was detected in 23 patients (7%) undergoing FIOC;
      only two of these patients with stones were in Group 1. Duct stones discovered by
      IOC were cleared laparoscopically in 89% of those attempted (73% of all
      patients). Neither morbidity nor duct injury caused by FIOC was noted.
      CONCLUSIONS: FIOC is much more rapid to perform than static IOC. Digital
      fluoroscopy is accurate and safe and permits rapid evaluation and management of
      bile duct stones. Selective use of FIOC efficiently assesses the common duct in
      the era of LC.

PMID- 7570325
TI  - Laparoscopic versus open inguinal herniorrhaphy: preliminary results of a
      randomized controlled trial.
AB  - BACKGROUND: Benefits of laparoscopic herniorrhaphy (LH) over open hernia repair
      (OH) remain unproved. METHODS: Interim analysis of a prospective randomized
      controlled trial compared OH with LH where study outcomes were measured by third
      party evaluators through patient interviews. RESULTS: Both groups were well
      matched for all baseline parameters, although LH patients anticipated a quicker
      postoperative recovery than OH (p = 0.014). No significant difference was noted
      in operating time or surgeon operative satisfaction. The median duration of
      hospital stay was 1 day in both groups; LH patients made use of significantly
      less postoperative narcotics than OH (p = 0.02). No difference was observed in
      the durations of convalescence (LH, 9.6 +/- 7.6 days; OH, 10.9 +/- 7.4 days).
      Greater improvements in quality of life were exhibited in LH patients than OH
      patients 1 month after operation (p = 0.035), with one of the two measures used.
      A greater percentage of LH patients seemed "very satisfied with their operation"
      (p = 0.07). Complication rates were similar, and a single recurrence, in a
      patient in the OH group, has been observed after a median follow-up of 14 months.
      CONCLUSIONS: Direct cost measurements showed LH to be 40% more expensive than OH
      in the context of a Canadian-type health care system. To date, benefits in
      postoperative pain and possibly quality of life have been detected in the LH
      group.

PMID- 7570326
TI  - Management considerations in Hurthle cell carcinoma.
AB  - BACKGROUND: Hurthle cell tumors still pose issues concerning diagnosis and
      management. METHODS: From 1984 to 1993 forty-seven patients underwent
      thyroidectomy, and they were diagnosed after operation to have presumptive
      Hurthle cell tumors. The surgical pathologic findings were reviewed. In the
      neoplastic group the chart was reviewed for clinical features and outcome.
      RESULTS: Thirty-one patients had nonneoplastic Hurthle cell nodules. Eleven (69%)
      of the 16 tumors were malignant affecting 11 women and five men ranging in age
      from 22 to 86 years. Two patients died of cancer for a 18% rate; one patient is
      alive with disease. Operations were uncomplicated. Factors for adverse outcome
      include tumor size greater than 4 cm, woman older than 60 years of age, and
      complete capsular invasion on surgical pathologic findings. CONCLUSIONS: Fine
      needle aspiration biopsy demonstration of Hurthle cell lesion is an indication
      for operation, providing Hashimoto's thyroiditis is excluded. Our surgical
      practice (I.B.R.) is to perform total thyroidectomy for all Hurthle cell
      neoplasms, as well as jugular node sampling and adjuvant radioiodine for cancer.
      Stringent histologic interpretation is possible and necessary for true
      appreciation of Hurthle cell tumor incidence and behavior. Cancer mortality of
      18% is greater than the rate (2%) of our well-differentiated thyroid cancer
      group.

PMID- 7570327
TI  - Definition of the role of enterococcus in intraabdominal infection: analysis of a
      prospective randomized trial.
AB  - BACKGROUND: The role of enterococcus in intraabdominal infection is
      controversial. This study examines the contribution of enterococcus to adverse
      outcome in a large intraabdominal infection trial. METHODS: A randomized
      prospective double-blind trial was performed to compare two different
      antimicrobial regimens in combination with surgical or percutaneous drainage in
      the treatment of complicated intraabdominal infections. A total of 330 valid
      patients was enrolled from 22 centers in North America. RESULTS: In 330 valid
      patients, 71 had enterococcus isolated from the initial drainage of an
      intraabdominal focus of infection. This finding was associated with a
      significantly higher treatment failure rate than that of patients without
      enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and
      Chronic Health Evaluation II score and presence of enterococcus were significant
      independent predictors of treatment failure when stepwise logistic regression was
      performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus
      include age, Acute Physiology and Chronic Health Evaluation II, preinfection
      hospital length of stay, postoperative infections, and anatomic source of
      infection. There was no difference between the clinical trial treatment regimens
      with regard to overall failure, failure associated with enterococcus, or
      frequency of enterococcal isolation. CONCLUSIONS: This study is the first to
      report enterococcus as a predictor of treatment failure in complicated
      intraabdominal infections. This trial also identifies several significant risk
      factors for the presence of enterococcus in such infections.

PMID- 7570328
TI  - Risk of dysplasia in anal condyloma.
AB  - BACKGROUND: Recent studies suggest an alarming incidence of dysplasia in
      homosexuals with anal condyloma. The purpose of our study was to determine the
      incidence of dysplasia in anal condyloma in our male patients and to determine
      risk factors for premalignant or malignant change. METHODS: Between 1986 and
      1994, 103 male patients were referred to our colorectal clinic for evaluation of
      anal condyloma. Ninety-one patients had biopsy for pathology and form the basis
      of this report. All charts were reviewed and results analyzed using the chi
      squared test with the Yates correction factor. RESULTS: Mean patient age was 31
      +/- 11 years (range, 13 to 78 years) and mean duration of disease was 20 +/- 26
      months (range, 2 to 120 months). There were 59 heterosexuals and 32
      homosexuals/bisexuals. Two heterosexuals (3%) had invasive squamous cell
      carcinoma and four (6%) had dysplasia. One homosexual/bisexual (3%) had squamous
      cell carcinoma in situ and nine (28%) had dysplasia (p < 0.05). Statistical
      analysis revealed that HIV seropositive status and disease location above the
      dentate line also predicted increased risk of dysplasia, whereas duration of
      disease, previous topical therapy, substance abuse, and other sexually
      transmitted diseases were not significant risk factors. CONCLUSIONS: Homosexual
      orientation, disease above the dentate line and HIV seropositivity increase the
      risk of dysplasia in perianal condyloma. The incidence of dysplasia in perianal
      condyloma is significant enough to warrant consideration of biopsy in all
      patients.

PMID- 7570329
TI  - Surgical treatment of obstructive pancreatitis.
AB  - BACKGROUND: Unlike chronic calcific pancreatitis, obstructive pancreatitis occurs
      as a consequence of an obstruction or stricture in the main pancreatic duct. The
      purpose of this paper is to identify the best method of surgical treatment for
      patients with obstructive pancreatitis. METHODS: Retrospective analysis of 224
      patients surgically treated for chronic pancreatitis during a 7-year period (1988
      through 1994) identified 23 patients with obstructive pancreatitis. Patients were
      classified by surgical treatment into pancreaticoduodenectomy (five patients),
      side-to-side pancreaticojejunostomy (nine patients), or distal pancreatectomy
      (nine patients) groups and analyzed. RESULTS: Despite similar demographics,
      patients treated with distal pancreatectomy had significantly better outcomes
      (seven of nine) than those treated with either pancreaticoduodenectomy (zero of
      four) or side-to-side pancreaticojejunostomy (two of eight) at a mean follow-up
      of 26 months (chi-squared, p = 0.009). Multivariate analysis revealed stricture
      location, cause of pancreatitis, maximal duct dilatation, exocrine insufficiency,
      or continued alcohol intake had no influence on surgical outcome in this series
      (p = 0.698, logistic regression analysis). CONCLUSIONS: At 2 years of follow-up,
      distal pancreatectomy provided superior relief from pain and recurrent
      pancreatitis compared with pancreaticoduodenectomy or side-to-side
      pancreaticojejunostomy. Obstructive pancreatitis is best treated by distal rather
      than proximal pancreatic resection or drainage.

PMID- 7570330
TI  - Polypropylene mesh closure after emergency laparotomy: morbidity and outcome.
AB  - BACKGROUND: Alternative methods for abdominal wall closure may be necessary after
      emergency laparotomy. The purpose of this study was to determine the morbidity
      and outcome of emergency fascial closure with polypropylene mesh. METHODS: A
      retrospective review was performed of all patients undergoing emergency fascial
      closure with polypropylene mesh from January 1990 to March 1994. RESULTS: Seventy
      patients were identified. Indications for mesh placement included visceral edema
      (40), infected/necrotic fascia (21), and planned reexploration (7). Enteric
      fistulas developed in five patients (7.1%). When omentum was interposed between
      intestine and mesh, the incidence of fistula was significantly reduced (0 of 51
      vs 5 of 19, p < 0.01). Forty-two patients (60%) survived with wound closure,
      accomplished by skin flaps in 19 (45%), skin grafting in 11 (26%), and secondary
      healing in 6 (14%). The mesh was removed in six patients (14%). Complications of
      mesh extrusion and hernia occurred less often after skin flap closure compared
      with skin grafting or secondary healing (1 of 19 vs 9 of 17, p < 0.01). No mesh
      infection occurred. CONCLUSIONS: Polypropylene mesh placement is an effective
      alternative for abdominal closure after emergency laparotomy, even when
      intraabdominal sepsis is present. Fistulas associated with its use may be
      effectively eliminated by the interposition of omentum between bowel and mesh.
      Wound closure with full-thickness skin flaps is the preferred method for soft
      tissue coverage when mesh is used.

PMID- 7570331
TI  - Should antibiotic prophylaxis be used routinely in clean surgical procedures: a
      tentative yes.
AB  - BACKGROUND: The incidence of surgical site infection (SSI) after clean surgical
      procedure has traditionally been regarded as too low for routine antibiotic
      prophylaxis. But we now know that host factors may increase the risk of SSI to as
      high as 20%. We assessed the value of prophylactic cefotaxime in patients
      stratified for risk of SSI in a randomized double-blind trial. METHODS: Patients
      admitted for clean elective operations were enrolled, stratified for risk by
      National Nosocomial Infection Survey criteria, and randomized to receive
      intravenous cefotaxime 2 gm or placebo on call for operation. They were followed
      for 4 to 6 weeks for SSI diagnosed by Centers for Disease Control and Prevention
      criteria. RESULTS: Analysis of 775 patients showed that the 378 evaluable
      patients who received cefotaxime had 70% fewer SSI than those who did not--Mantel
      Haenszel risk ratio (MH-RR) 0.31; 95% confidence intervals (CI) 0.11 to 0.83.
      Benefit was clear in the 616 low risk patients--0.97% versus 3.9% SSI (MH-RR
      0.25, CI 0.07 to 0.87, p = 0.018), but only a trend was seen in 136 high risk
      patients--2.8% versus 6.1% SSI (MH-RR 0.48, CI 0.09 to 2.5). CONCLUSIONS: The
      results indicate clear benefit for routine antibiotic prophylaxis in clean
      surgical procedures. High risk patients need more study.

PMID- 7570332
TI  - Prospective analysis of perioperative morbidity in one hundred consecutive
      colectomies for ulcerative colitis.
AB  - BACKGROUND: This study was undertaken to evaluate prospectively the indications
      for surgical treatment and perioperative morbidity for patients with idiopathic
      ulcerative colitis (UC). METHODS: Between January 1985 and August 1994, 145
      patients were referred to the senior author (F.M.) for treatment of UC. Data were
      prospectively collected. One hundred patients have completed all stages of their
      surgical treatment and have been followed up for at least 1 year. These 100
      patients form the basis of this study. RESULTS: Thirty patients underwent a
      proctocolectomy with end-ileostomy in one (25) or two (5) stages. Seventy
      patients underwent a restorative proctocolectomy with ileal J-pouch anal
      anastomosis in either one (2), two (37), or three stages (31). In total 100
      patients underwent 204 procedures. Failure of medical treatment was by far the
      most common indication. The initial colectomy was performed electively in 61
      patients and urgently in the remaining 39. The rate of perioperative
      complications for elective and urgent colectomy was 26% and 44%, respectively (p
      < 0.05). CONCLUSIONS: The overall perioperative morbidity rate remains high and
      almost doubles for urgent cases. Reducing the need for urgent procedures by
      earlier elective colectomy may allow for a reduction in perioperative morbidity.

PMID- 7570333
TI  - Tumor necrosis factor-alpha and total parenteral nutrition-induced anorexia.
AB  - BACKGROUND: We hypothesize that total parenteral nutrition (TPN) induces anorexia
      by an increase in anorexigenic cytokines (factors with central action via the
      hypothalamus) and tested this hypothesis by measuring changes in food intake and
      cytokines in response to TPN. METHODS: Fischer rats with an internal jugular
      catheter and ad libitum food received saline solution for 10 days. On day 11,
      rats were randomized to TPN (G:F:AA = 50:30:20) for 4 days (days 11 through 14);
      control rats received on saline solution for 5 days. On day 14, one half of the
      TPN group was switched back to saline solution for 1 day. Daily food intake was
      measured. On day 14 in one half of all rats and on day 15 in the remaining, tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1 alpha were measured in plasma
      and cerebrospinal fluid (CSF). Spontaneous in vitro TNF-alpha and IL-1 alpha were
      also measured in peripheral blood mononuclear cells. RESULTS: With TPN, an 80%
      decrease (p < 0.01) in food intake occurred; plasma TNF-alpha increased (78 +/- 9
      pg/ml vs undetectable; p < 0.001), and IL-1 alpha was undetectable. Spontaneous
      in vitro TNF-alpha and IL-1 alpha production were unchanged. Stoppage of TPN led
      to return toward normal of food intake and plasma TNF-alpha. TNF-alpha and IL-1
      alpha in CSF were undetectable in both groups during and after TPN. CONCLUSION:
      Increase in plasma TNF-alpha with no increase in CSF-TNF-alpha during TPN, when
      food intake decreased, suggests an association between TPN and TNF-alpha but not
      necessarily cause and effect.

PMID- 7570334
TI  - Arterial reconstruction for limb salvage: is the terminal peroneal artery a
      disadvantaged outflow tract?
AB  - BACKGROUND: Arterial reconstructions performed for limb salvage have increasingly
      used distal perimalleolar and pedal arteries as outflow tracts. However, a
      paucity of reports comparing the patency and limb salvage rates of these outflow
      tracts has been published. In this report we examine our experience with distal
      peroneal artery reconstructions for limb salvage. METHODS: During the past 14
      years 159 bypasses were performed to the distal peroneal artery (within 5 cm of
      the malleolus), 157 of which were performed by the medial approach and two by the
      lateral approach. RESULTS: Sixty-three percent of the patients were male, 65%
      were diabetics, and 43% were smokers; the average age was 72.6 years. Sixty-five
      percent of the bypasses were performed with the in situ technique. Thirty-one
      percent of the bypasses were performed with translocated or spliced vein
      technique, and seven (4%) were performed with prosthetic technique. Secondary
      patency rates for distal peroneal artery bypass grafts at 1 and 5 years were 86%
      and 75%. The limb salvage rate for distal peroneal artery bypasses was 87% at 5
      years. Four hemodynamic failures occurred in this group. Wound complications
      requiring revision were seen in one patient with a distal peroneal bypass (0.6%).
      These results do not differ from our results with other perimalleolar vessels.
      CONCLUSIONS: Arterial reconstruction to the distal peroneal artery has acceptable
      patency and limb salvage rates. These bypasses are as effective and durable as
      other perimalleolar bypasses.

PMID- 7570335
TI  - Experimental liver cancer: improved response after hepatic artery ligation and
      infusion of tumor necrosis factor-alpha and interferon-gamma.
AB  - BACKGROUND: The aim of this study is to investigate whether regional infusion of
      tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) could
      improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer
      in a rat model. METHODS: Morris hepatoma 3924A was implanted intrahepatically in
      50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery
      cannulation and ligation. The cannula was connected to an infusion port implanted
      subcutaneously. Animals were then divided into four groups of 10 each to receive
      seven daily intraarterial injections of IFN-gamma 100,000 IU/rat/day (HAL + IFN
      group), TNF-alpha 30 micrograms/rat/day (HAL + TNF group), IFN + TFN (HAL + IFN +
      TNF group), or normal saline solution (HAL group). The remaining 10 rats received
      a laparotomy only and served as untreated controls. Tumor volume, viable tumor
      area, and histopathology were assessed after 3 weeks. RESULTS: The tumor growth
      was significantly retarded in the HAL group compared with the controls (tumor
      volume 683 +/- 245 mm3 vs 2424 +/- 596 mm3, p < 0.05 ANOVA). HAL + TNF (221 +/-
      93 mm3) and HAL + IFN + TNF groups (74 +/- 31 mm3), but not the HAL + IFN group
      (493 +/- 164 mm3), were much more effective than the HAL group in controlling
      tumor growth (p < 0.05). HAL + IFN + TNF achieved the best tumor control
      resulting in a 60% tumor-free rate (p < 0.05 vs all other groups). CONCLUSIONS:
      These data suggest that HAL combined with regional infusion of TNF-alpha and IFN
      gamma significantly reduces tumor growth in a rat liver model. This attractive
      concept of combined modality therapy may have utility in the clinical setting in
      instances of unresectable liver cancer.

PMID- 7570337
TI  - Corticosteroid withdrawal after liver transplantation.
AB  - BACKGROUND: Long-term side effects of corticosteroids (CSs) result in > major
      morbidity for recipients of orthotopic liver transplants (OLT). We instituted a
      program of CS withdrawal among OLT recipients to quantify the contribution of CS
      to adverse clinical sequelae and to determine whether long-term CS administration
      is necessary to avoid rejection. METHODS: Recipients who had normal allograft
      function on CS, cyclosporine, and azathioprine more than 1 year after OLT were
      offered CS withdrawal during 12 to 22 weeks. Patients underwent routine clinical
      monitoring and laboratory studies. Continuous variables were compared by paired t
      test analysis. RESULTS: CSs were discontinued in 51 recipients; 45 (88%) of 51
      patients remain steroid-free after a mean follow-up of 13.8 months (range, 4 to
      36). CS therapy was reinstituted in 6 patients who had abnormal transaminase
      levels during routine follow-up. Among the patients who remain off CS, there were
      no significant changes in blood pressure, transaminase, alkaline phosphatase,
      bilirubin, or glucose levels during the study period. Mean number of blood
      pressure medications decreased from 0.7 +/- 0.1 to 0.4 +/- 0.1 (p = 0.007).
      Cholesterol decreased from 217 +/- 8 mg/dl on CS to 204 +/- 9 mg/dl at 1 month (p
      = 0.0001), 183 +/- 10 mg/dl at 3 months (p = 0.0001), 198 +/- 8 mg/dl at 6 months
      (p = 0.04), 213 +/- 11 mg/dl at 12 months (p = 0.01), 209 mg/dl +/- 16 at 18
      months (p = 0.02), and 183 +/- 19 mg/dl at 24 months (p = 0.2) off CS. Weight
      loss occurred in 88% of patients and averaged 9.5 pounds. CONCLUSIONS: CS therapy
      can be successfully withdrawn without precipitating rejection in liver transplant
      recipients who have stable graft function 1 year after OLT. The incidence and
      severity of hypertension and hypercholesterolemia are reduced in patients whose
      CSs have been withdrawn.

PMID- 7570336
TI  - Pathogenesis-based treatment of recurring subareolar breast abscesses.
AB  - BACKGROUND: When a subareolar breast abscess (SBA) is incised and drained, an
      extraordinarily high frequency of recurrence is noted. METHODS: To develop a
      pathogenesis-based treatment plan, 24 women with a total of 84 abscesses were
      monitored. RESULTS: In nine women SBA was under the left areola, under the right,
      in 7 and in eight the SBA occurred either simultaneously or sequentially under
      both areolae. In 11 of 24 patients a chronic lactiferous duct fistula also
      existed. In four of 24 patients four SBAs were treated with antibiotics; alone;
      all recurred. In 16 of 24 patients initial treatment was incision and drainage
      plus antibiotics; all recurred. When the abscess plus the plugged lactiferous
      duct was excised, there were no recurrences; however, in four patients a new
      abscess in a different duct occurred, which was treated by en bloc resection of
      all subareolar ampullae, without further recurrence. Patients with a fistulous
      tract had the fistula, its feeding abscess, and its plugged lactiferous duct
      excised, without recurrence. In first time SBA the organism was usually
      staphylococcus; in recurrences mixed flora was isolated. Pathologic findings
      ranged from squamous metaplasia with keratinization of lactiferous ducts to
      chronic abscess. CONCLUSIONS: The cause of SBA is plugging of lactiferous duct
      within the nipple by keratin. To prevent recurrence the abscessed ampulla with
      its plugged proximal duct needs excision.

PMID- 7570338
TI  - Prehospital classification combined with an in-hospital trauma radio system
      response reduces cost and duration of evaluation of the injured patient.
AB  - BACKGROUND: This study was undertaken to determine whether a prehospital trauma
      classification system (PHTCS) in combination with an in-hospital trauma radio
      system response (IHTRSR) impacts emergency care of the injured patient. METHODS:
      In 1991 our trauma center used no prehospital trauma classification system. A
      PHTCS was implemented in 1992, and in 1993 the PHTCS was integrated with an
      IHTRSR: RESULTS: Implementation of the PHTCS and IHTRSR resulted in a significant
      reduction in the time required for initial evaluation of the trauma patient with
      an associated reduction in cost. Reduction in time of the initial trauma
      evaluation was noted in both adult and pediatric populations, in patients with a
      blunt mechanism of injury, and in the injured patients posing the greatest strain
      to health care resources. CONCLUSIONS: Integration of a PHTCS with an IHTRSR has
      a significant impact on the cost and time of emergency treatment of the trauma
      victim with no adverse effect on patient outcome. Use of an integrated trauma
      response provides cost-effective and expeditious care of the injured patient and
      should be considered in trauma system development.

PMID- 7570340
TI  - Chronic corticosterone treatment maintains synaptic activity of CA1 hippocampal
      pyramidal cells: acute high corticosterone administration increases action
      potential number.
AB  - The hypothalamic-pituitary-adrenocortical (HPA) axis controls the levels of
      plasma corticosterone (CT) in the rat and the levels of cortisol in man. CT is
      important in maintaining homeostasis and regulating energy production.
      Homeostasis is maintained by basal activation of the hippocampal-HPA axis. In
      response to stress CT secretion is increased. CT activation of receptors in the
      hippocampus provides feedback inhibition of the HPA axis to return the system to
      basal activity. There are two types of CT receptors: the mineralocorticoid
      receptor (MR) and the glucocorticoid receptor (GR). CT has a 10-fold higher
      affinity for MR than GR. Normal basal levels of CT occupy the majority of the MR.
      During the diurnal surge of CT and following the presentation of a stressful
      stimulus, the MR and GR are both maximally occupied. To begin to understand how
      CT influences the hippocampal-HPA axis, intracellular recording techniques in the
      hippocampal brain slice preparation were used to determine how high
      concentrations of CT may alter cell characteristics and/or evoked synaptic
      activity. Two treatment groups were used, i.e., adrenalectomized (ADX) and ADX
      with CT pellet replacement (ADX+CT) that produced plasma blood levels equal to
      that seen in a normal rat in the morning. Acute administration of 100 nM CT
      decreased action potential threshold and the number of action potentials elicited
      by a depolarizing current pulse in cells from both the ADX and ADX+CT treated
      rats. The amplitude of the evoked excitatory postsynaptic potentials (EPSP) or
      inhibitory postsynaptic potentials (IPSP) declined in cells recorded from ADX
      animals and ADX rats acutely treated with high concentrations of CT
      (ADX/CT).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570339
TI  - Binding and internalization of neurotensin in hybrid cells derived from septal
      cholinergic neurons.
AB  - Autoradiographic studies from our laboratory have previously demonstrated a
      selective association of high affinity neurotensin (NT) binding sites with basal
      forebrain cholinergic neurons. In search of an in vitro model for further
      characterization of the role and regulation of these sites, we have examined the
      binding and internalization of 125I-Tyr3-NT (125I-NT) and fluorescein
      isothiocyanate (FITC)-conjugated NT (fluo-NT) on SN17 hybrid cells, produced by
      fusion of embryonic murine septal cells with neuroblastoma. 125I-NT binding to
      SN17 membrane preparations was specific and saturable. Scatchard analysis of the
      data was suggestive of an interaction with a single population of sites, the
      affinity (Kd = 1.7 nM) and pharmacological profile of which were comparable to
      those of neural NT receptors. No specific binding was observed on the parent
      neuroblastoma cell line, confirming that the expression of those sites is a
      neuronal trait. Incubation of whole SN17 cells with 125I-NT resulted in a time-
      and temperature-dependent internalization of the specifically bound peptide. The
      t1/2 of this internalization was estimated at 13 min, a value nearly identical to
      that reported for neurons in culture. Confocal microscopic analyses using fluo-NT
      indicated that the internalization process was endocytic in nature in that: 1) it
      was entirely blocked by the endocytosis inhibitor phenylarsine oxide; and 2) it
      was mediated through small intracytoplasmic particles the size and maturation of
      which corresponded to that of endosomes. It is proposed that the expression and
      internalization of NT receptors by SN17 hybrid cells represent a new facet of
      these cells' cholinergic phenotype that makes them amenable to the study of NT
      interactions with cholinergic cells.

PMID- 7570341
TI  - Neonatal excitotoxic ventral hippocampal damage alters dopamine response to mild
      repeated stress and to chronic haloperidol.
AB  - The effects of neonatal excitotoxic ventral hippocampus (VH) lesions on dopamine
      release in response to repeated stress (saline injections) and to chronic
      haloperidol treatment were investigated in Sprague-Dawley rats infused with
      ibotenic acid or vehicle into the VH on day 7 of postnatal life (PD7). Beginning
      on PD35, lesioned and sham-operated rats were injected i.p. with saline (INJ)
      once daily for 3 weeks or were not treated (NO INJ). Another cohort of rats was
      given haloperidol (HAL, 0.4 mg/kg, i.p.) or vehicle beginning on PD35 and
      thereafter once daily for 3 weeks. 3-Methoxytyramine (3-MT) was measured by
      combined gas chromatography/mass spectrometry in the frontal cortex (FC), nucleus
      accumbens (NAcc), and striatum (STR) at PD56 following MAO inhibition with
      pargyline. At baseline (NO INJ), 3-MT was reduced in STR of lesioned rats.
      Repeated saline injections resulted in a further 3-MT reduction in STR, FC, and
      NAcc of lesioned animals, but had no effect in sham rats. Chronic HAL, compared
      with vehicle, suppressed locomotor activity, and increased 3-MT accumulation in
      the FC, NAcc, and STR in sham and lesioned rats. This increase was enhanced in
      the FC of lesioned rats. These data show that mild repeated stress attenuates
      dopamine release in FC, NAcc, and STR of lesioned rats, while chronic HAL
      augments it in FC of lesioned animals versus controls. We conclude that the
      neonatal excitotoxic lesion of VH alters the functioning of midbrain dopamine
      systems during environmental and pharmacological challenge.

PMID- 7570342
TI  - Outward potassium currents activated by depolarization in rat globus pallidus.
AB  - Voltage-dependent potassium currents play a key role in shaping the firing
      pattern of central neurons. Their pharmacological and physiological
      identification is rather important in the structures which are involved in the
      filtering of input/output messages. In this regard, globus pallidus external
      segment (GPe) is indicated as a crucial station in the well-known indirect
      pathway of the basal ganglia. Among the potassium conductances which have been
      indicated to condition the firing behavior and the neuronal integrative
      properties in many central neurons, we analysed the depolarization-activated ones
      by means of patch-clamp recordings in the whole-cell configuration. Two main
      families of calcium-independent outward potassium currents are activated by
      depolarization in GPe neurons acutely isolated from the adult rat. From
      depolarized holding potentials (-50/-45 mV), a slowly-activating, sustained
      current is evoked; it manifests very little inactivation and it is available at
      rather depolarized potentials (-30 mV/-20 mV). This current is relatively
      resistant to 4-aminopyridine (4-AP) but it is blocked by tetraethilammonium ions
      (TEA) and consequently it resembles delayed rectifier current (Ik). From negative
      holding potentials (-80/-100 mV), on the other hand, A-like conductances are
      activated. Together with a fast-inactivating transient current, another component
      is observed in a significant proportion of recordings (45%). This current shows
      half-inactivation voltage around -90 mV, peculiar sensitivity to micromolar doses
      of 4-AP and a slow rate of recovery from inactivation. The presence and the
      modulation of these A-like currents may be a very critical aspect in the membrane
      physiology of pallidal neurons.

PMID- 7570343
TI  - Sensitivity of striatal [11C]cocaine binding to decreases in synaptic dopamine.
AB  - We have previously shown that tracer concentrations of [11C]cocaine binding to
      the dopamine transporter (DAT) in human and baboon striatum can be visualized
      using positron emission tomography (PET). To determine whether the concentration
      of dopamine normally present in the synaptic cleft can compete with [11C]cocaine
      for transporter binding sites, we conducted baboon PET studies with drugs (sodium
      4-hydroxybutyrate, four studies, 200 mg/kg; gamma-vinylGABA, three studies, 300
      mg/kg; and citalopram, three studies, 2 mg/kg) expected to decrease synaptic
      dopamine. Each study involved two [11C]cocaine injections and PET scans separated
      by 2-4 h, with drug administration after the first injection, and without
      movement of the subject between scans. Time-activity data from striatum and from
      cerebellum were used with the arterial plasma input function to determine
      graphically by Logan plotting [11C]cocaine distribution volumes for the brain
      regions. Specific binding of [11C]cocaine to DAT in striatum was calculated as
      the distribution volume ratio (DVR) for striatum and cerebellum. In nine of the
      ten studies drug treatment produced a small increase in DVR (range, 1-11%), and
      in seven of these studies the increase was > or = 7%. The mean increase was 6.2
      +/- 4.1%. The reproducibility of the DVR measure was assessed by comparing
      [11C]cocaine studies conducted without pharmacological treatments using
      individual baboons on separate days, and thus involving possible repositioning
      errors, as well as long-term changes in the state of the striatal dopamine
      system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570344
TI  - Brain somatostatin receptors in a rat model of acute liver failure.
AB  - The present study examines the effect of acute liver failure induced by a single
      intraperitoneal (i.p.) injection of D-galactosamine-HCl (3 g/kg) on somatostatin
      (SS) binding and levels in the rat frontoparietal cortex and hippocampus.
      Neurobehavioural changes were evaluated by the method of Zieve et al. [(1984) J.
      Lab. Clin. Med., 104:655-664]. The rats were decapitated as soon as they reached
      neurobehavioural stage I or II. In stage I, rats had lethargy and in stage II
      they showed mild ataxia, mainly in the hind limbs. The administration of D
      galactosamine elevated serum transaminase levels (mean peak level 2,242 IU/1) but
      hypoglycemia, gross cerebral edema, or signs of sepsis were not detected in any
      of the animals studied. In addition, D-galactosamine did not affect somatostatin
      like immunoreactivity (SSLI) levels in either brain area in any of the
      experimental groups as compared to the control groups. The rats sacrificed in
      stage I showed no change in the number or affinity of specific 125I-Tyr11
      somatostatin (125I-Tyr11-SS) receptors in synaptosomes from the frontoparietal
      cortex and hippocampus. The rats sacrificed in stage II showed a decrease in the
      number of specific 125I-Tyr11-SS receptors in synaptosomes from both brain areas,
      with no change in receptor affinity. Binding studies were also conducted on
      synaptosomes from the frontoparietal cortex and hippocampus of rats that received
      D-galactosamine but did not develop acute liver failure and consequently did not
      develop neurobehavioural changes. The SS receptors in these synaptosomes did not
      change in comparison with controls, indicating that the D-galactosamine was not
      directly responsible for the changes in the cerebral SS receptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7570345
TI  - Biochemical and electrophysiological effects of 7-OH-DPAT on the mesolimbic
      dopaminergic system.
AB  - Systemic administration of the putative selective D3 receptor agonist 7-hydroxy-2
      (N,N-di-n-propylamino)tetralin (7-OH-DPAT) consistently decreased extracellular
      dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus
      accumbens and dopaminergic neuronal activity in the ventral tegmental area. 7-OH
      DPAT inhibited dopamine release in the nucleus accumbens also when locally
      perfused through the dialysis probe. The results suggest the possibility that
      stimulation of dopamine D3 receptors with 7-OH-DPAT mimic biochemical and
      electrophysiological actions previously ascribed to D2 autoreceptor stimulation;
      however the lack of selective D3 antagonist precludes any firm conclusion in this
      sense.

PMID- 7570346
TI  - Neuroprotective sigma ligands interfere with the glutamate-activated NOS pathway
      in hippocampal cell culture.
AB  - We studied neuroprotective properties of 12 structurally different sigma site
      ligands in primary rat hippocampal cell cultures and analyzed whether they
      interfere with glutamate-induced activation of the nitric oxide synthase (NOS)
      pathway. Neurotoxicity was triggered with 1 mM glutamate on day 8 of culture.
      Cells were treated with various concentrations of the compounds for 7 days before
      glutamate exposure (prolonged pretreatment), or during glutamate exposure (acute
      treatment). Protection was seen after prolonged pretreatment (long-term
      protection) with sabeluzole, opipramole, haloperidol, ifenprodil, fenpropimorph,
      carbetapentane, and tiospirone, with pIC50s of 7.30, 7.15, 6.87, 6.68, 6.66,
      6.39, and 6.34, respectively. There was no protection with PD 128298, 1,3-ortho
      di-tolylguanidine, BMY-14802, (+)3-(3-hydroxyphenyl)-N-1(propyl) piperidine, or
      dextromethorphan. Upon acute treatment, only ifenprodil was protective.
      Interference of the drugs with glutamate activation of the NOS pathway was
      determined by measuring glutamate-activated cGMP formation and citrulline levels.
      Glutamate-activated cGMP formation was reduced by all neuroprotective sigma
      ligands after prolonged pretreatment but not after acute treatment. Sigma ligands
      added to cell culture lysate did not reduce citrulline formation, evidence that
      there was no direct effect on the NOS enzyme. We conclude that some but not all
      sigma ligands exert long-term protective properties against glutamate-induced
      neurotoxicity in primary hippocampal cultures, and that this protection is
      accompanied by attenuation of cGMP formation in the NOS pathway. However,
      inhibition of cGMP formation by itself appeared not sufficient for obtaining
      neuroprotective effects, as inhibition of glutamate-activated cGMP formation by N
      omega-nitro-L-arginine, haemoglobin, or PD128298 did not provide neuroprotection.

PMID- 7570347
TI  - Distribution of GABAA receptor alpha 1 subunit-like immunoreactivity in
      comparison with that of enkephalin and substance P in the rat forebrain.
AB  - The gamma-aminobutyric acid-A receptor consists of several subunits. In this
      immunohistochemical study we investigated the regional distribution of the alpha
      1 subunit with an antibody directed against a specific amino acid sequence (1-9)
      of the (1-9) of the alpha 1 subunit. We compared the distribution pattern of the
      alpha 1 subunit-like immunoreactivity with that of substance P- and enkephalin
      like immunoreactivities in adjacent sections of the rat forebrain. alpha 1
      subunit-like immunoreactivity appeared in the form of varicosities and fibers. A
      band-like terminal staining pattern (woolly fibers) that has been shown by others
      for substance P- and enkephalin-like immunoreactivity is also observed for alpha
      1 subunit-like immunoreactivity. In contrast to substance P and enkephalin,
      numerous alpha 1 subunit-like immunoreactive perikarya were found. The highest
      density of alpha 1 subunit-like immunoreactive fibers and perikarya was found in
      the pallidal areas and the substantia nigra pars reticulata whereas the nucleus
      accumbens and the caudate putamen displayed a low density. alpha 1 subunit-like
      immunoreactive neurons resembled typical pallidal neurons. Some of these neurons
      were pericellularly stained with enkephalin-like immunoreactive varicosities in
      the dorsal pallidum. The distribution pattern of alpha 1 subunit-like
      immunoreactivity reflects a partial overlap with the substance P and enkephalin
      system although a differential distribution to each of these peptides was
      observed for cell bodies, fibers, and axon terminals.

PMID- 7570348
TI  - Neuropharmacology of the nucleus accumbens: iontophoretic applications of
      morphine and nicotine have contrasting effects on single-unit responses evoked by
      ventral pallidal and fimbria stimulation.
AB  - Extracellular recordings within the nucleus accumbens (NAS) of halothane
      anesthetized rats have revealed that iontophoretically applied morphine and
      nicotine have contrasting effects on neuronal responses evoked by fimbria or VP
      stimulation. Iontophoretically applied morphine inhibited NAS single-unit
      responses evoked by VP stimulation but did not affect unit responses evoked by
      fimbria stimulation. In contrast, iontophoretically applied nicotine had no
      effect on NAS single-unit responses evoked by VP stimulation but inhibited single
      unit responses evoked by fimbria stimulation. Spontaneously active NAS units were
      inhibited by iontophoretically applied morphine but were unaffected by nicotine.
      In addition, experiments were conducted to determine whether NAS unit responses
      to electrical stimulation of the VP were likely to involve cell body as opposed
      to axonal activations. Selective cell body stimulation by glutamate micro
      infusions into the VP region excited spontaneously active VP single-units.
      Concurrently recorded NAS unit responses to electrical stimulation of the VP were
      also excited. These results are consistent with the idea that NAS evoked
      responses to VP electrical stimulation involve somal activation. Generally, these
      results suggest a specific neuropharmacological organization of the NAS. Analysis
      of the effects of morphine and nicotine on other NAS circuits will establish a
      systems level understanding of NAS responses to reinforcers.

PMID- 7570349
TI  - Effect of destruction of serotonin neurons on basal and fenfluramine-induced
      serotonin release in striatum.
AB  - This study examined the relationship between the magnitude of tissue serotonin (5
      HT) depletion produced by treatment with the neurotoxin 5,7-dihydroxytryptamine
      (5,7-DHT) and basal and fenfluramine-induced 5-HT release in the striatum.
      Separate groups of rats were treated with either vehicle or 5,7-DHT (100
      micrograms: 76% striatal 5-HT depletion; or 200 micrograms: 93% striatal 5-HT
      depletion). Four weeks after treatment, 5-HT release was measured in the ventral
      striatum using in vivo microdialysis in animals anesthetized with chloral
      hydrate. Basal 5-HT levels were not significantly altered in any lesion group,
      whereas basal 5-hydroxyindoleacetic acid levels were dose-dependently reduced by
      5,7-DHT. In contrast, the increase of 5-HT release produced by fenfluramine
      treatment (10 mg/kg) was diminished significantly after 5-HT neuronal destruction
      in correlation with the reduction of striatal tissue 5-HT content. Fractional 5
      HT efflux, a measure of the 5-HT release from surviving striatal nerve terminals,
      was also significantly elevated when tissue depletion of 5-HT exceeded 95%. This
      study suggests that compensatory mechanisms may enable surviving 5-HT terminals
      to maintain basal 5-HT levels in the striatum with as little as 5% of the
      terminals remaining, but those mechanisms are not sufficient to allow the damaged
      system to respond to a pharmacological challenge.

PMID- 7570350
TI  - Antibodies to calcium channels from ALS patients passively transferred to mice
      selectively increase intracellular calcium and induce ultrastructural changes in
      motoneurons.
AB  - Antibodies to Ca channels in ALS patients IgG can be demonstrated to enhance Ca
      current and cause cell injury and death in a motoneuron cell line in vitro. To
      determine whether these antibodies can alter neuronal calcium homeostasis in vivo
      IgG fractions from six ALS patients were injected intraperitoneally into mice,
      and neurons assayed by ultrastructural techniques for calcium content. After 24
      h, all six ALS IgG by (40 mg/animal) increased vesicle number in spinal
      motoneuron axon terminals, and in boutons synapsing on spinal motoneurons. Using
      the oxalate-pyroantimonate technique for calcium precipitation, these antibodies
      produced dose-dependent calcium increases either in axon terminal synaptic
      vesicles and mitochondria, or in rough endoplasmic reticulum, mitochondria, and
      Golgi complex of spinal motoneuron and frontal cortex pyramidal cells. ALS IgG
      was itself internalized and also induced neurofilament H phosphorylation. The
      observed changes in ultrastructure and calcium compartmentation were restricted
      to motoneurons; normal and disease control IgG, which did not possess antibodies
      enhancing calcium entry, did not exert similar effects. These data demonstrate
      that ALS IgG containing Ca-channel antibodies can alter calcium homeostasis of
      motoneurons in vivo.

PMID- 7570351
TI  - Variability in D2-dopamine receptor density and affinity: a PET study with
      [11C]raclopride in man.
AB  - The variability of D2-dopamine receptor binding parameters in man was determined
      using Positron Emission Tomography (PET) and [11C]raclopride. A saturation
      analysis based on five PET-experiments was performed in each of ten men and ten
      women. The mean density of D2-dopamine receptors (Bmax) was 28 +/- 6.9 pmol/ml
      (mean +/- S.D.) and the apparent affinity (Kdapp) 9.1 +/- 1.9 pmol/ml. The Hill
      coefficient was in all subjects close to unity (nH: 0.999 +/- 0.020), thereby
      indicating binding to a homogeneous class of receptors. No significant
      differences between males and females were found in Bmax or Kdapp. The
      interindividual difference in Bmax was statistically significant (alpha = 0.01).
      The difference in Kdapp was not significant. Upregulation of the receptor density
      (Bmax) has been widely discussed as a mechanism for increased dopaminergic
      neurotransmission in schizophrenia. This study indicates that receptor density
      varies considerably in a group of healthy subjects.

PMID- 7570353
TI  - Application of a protein synthesis inhibitor into the ventral tegmental area, but
      not the nucleus accumbens, prevents behavioral sensitization to cocaine.
AB  - Recent evidence implicates a crucial role for the ventral tegmental area (VTA) in
      the initiation of behavioral sensitization produced by repeated psychostimulant
      exposure, while changes in the nucleus accumbens (NAcc) are not critical during
      the initiation stage. We investigated whether the development of behavioral
      sensitization to repeated daily cocaine could be prevented by daily
      administration of the protein synthesis inhibitor, anisomycin, delivered onto VTA
      neurons. Rats were given five daily treatments as follows: obturators containing
      crystalline anisomycin or no compound (sham) were placed directly into the VTA 15
      min prior to a saline (1 ml/kg, i.p.) or cocaine (15 mg/kg, i.p.) injection.
      After withdrawal for 8-9 days, the locomotor response to the same dose of saline
      or cocaine was monitored. No differences in the locomotor response to an acute
      saline challenge were found across the four groups. Animals given sham treatments
      in the VTA and daily cocaine demonstrated a significant augmentation in the
      locomotor response to a cocaine challenge compared to saline controls. Anisomycin
      treatments alone produced no effects on acute cocaine-induced locomotion.
      Further, a cocaine challenge in animals receiving daily anisomycin and cocaine
      elicited a non-augmented response similar to that of saline controls. Thus, the
      sensitized locomotor response to a cocaine challenge in daily cocaine pretreated
      animals was completely blocked by daily anisomycin treatment in the VTA. When
      daily anisomycin was administered into the NAcc along with daily cocaine, no
      blockade of behavioral sensitization was observed. These results provide support
      for a critical role of long-term changes in gene expression in the vicinity of
      VTA neurons mediating the development of sensitization to psychostimulants.

PMID- 7570352
TI  - Repeated quinpirole treatment: locomotor activity, dopamine synthesis, and
      effects of selective dopamine antagonists.
AB  - Repeated treatment with the non-selective dopamine agonist apomorphine results in
      behavioral sensitization and enhanced dopamine synthesis in dopamine projection
      fields. To examine the role of D2-type dopamine receptors in modulating these
      effects, the present experiment assessed the effects of repeated treatment with
      the D2-type agonist quinpirole on locomotor activity and dopamine synthesis. In
      the first experiment, rats were treated with vehicle or one of two doses (0.3 or
      3.0 mg/kg) of quinpirole for 8 days. Daily measures of locomotor activity
      revealed an initial suppression of activity produced by quinpirole which
      dissipated over the 8 days of treatment. A trend for an increase in activity for
      3.0 mg/kg quinpirole compared to vehicle was obtained on day 8. Twenty-four hours
      after cessation of treatment, dopamine synthesis, measured as accumulation of 3,4
      dihydroxyphenylalanine (DOPA) after treatment with the DOPA decarboxylase
      inhibitor NSD-1015, was enhanced in the striatum, but not nucleus accumbens
      olfactory tubercle (NAOT) or ventral mesencephalon (VM). In Experiment 2, rats
      were treated for 8 days with vehicle, 3.0 mg/kg quinpirole or the D1 antagonist
      SCH 23390 (0.5 mg/kg) in a two (vehicle or quinpirole) x two (vehicle or SCH
      23390) design. Quinpirole-alone treatment resulted in a reduction of the
      locomotor suppressant effects of the drug. SCH 23390-alone and quinpirole-SCH
      23390 combined treatment resulted in decreased activity compared to the vehicle
      control group that did not change across days. DOPA accumulation was enhanced in
      the striatum and NAOT after quinpirole treatment; however, SCH 23390 had no
      effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570354
TI  - Systemic uptake inhibition decreases serotonin release via somatodendritic
      autoreceptor activation.
AB  - In vivo microdialysis was used to examine the effects of peripheral uptake
      inhibition on extracellular serotonin (5-HT). Previous results from this lab
      indicated that systemic fluoxetine caused a decrease in 5-HT when terminal uptake
      was inhibited by local infusion of the uptake blocker. We hypothesized that the
      decrease in 5-HT levels in the terminal region was due to an increase in 5-HT in
      the vicinity of the inhibitory somatodendritic autoreceptors in the dorsal raphe
      nucleus (DRN). To test this prediction, rats were implanted with probes in both
      the basal diencephalon (a nerve terminal region) and the DRN (the cell body
      region). Fluoxetine (10 mg/kg i.p.) increased extracellular 5-HT, in a
      depolarization-dependent manner, by approximately 140% in both areas. In a
      separate experiment, fluoxetine was infused into the diencephalon overnight to
      block nerve terminal uptake sites. This pretreatment caused an eight- to 10-fold
      increase in 5-HT levels. Subsequent systemic fluoxetine, sertraline, or
      paroxetine, produced a 50% decrease in extracellular 5-HT in the diencephalon,
      presumably due to activation of the 5-HT1A somatodendritic autoreceptors.
      Consistent with this hypothesis, systemic administration of the 5-HT1 antagonists
      spiperone, penbutolol, or WAY100135 reversed the fluoxetine-induced decrease in 5
      HT to approximately 85% of the pre-fluoxetine baseline levels. Likewise,
      pretreatment with penbutolol, but not selective beta-adrenergic antagonists,
      blocked the fluoxetine-induced decrease in release. These findings suggest that
      the ability of acute systemic 5-HT uptake inhibition to elevate nerve terminal 5
      HT is limited by autoreceptor activation following elevation of 5-HT in the DRN.

PMID- 7570355
TI  - Ultrastructural correlates of haloperidol-induced oral dyskinesias in rat
      striatum.
AB  - Neuroleptics given chronically to rats induce behavioral sequelae which mimic
      tardive dyskinesia in some respects. The intent of this study was to investigate
      the ultrastructural correlates of oral dyskinesias (vacuous chewing movements
      [VCMs]), induced by chronic haloperidol treatment. After 6 months of treatment,
      rats were divided into low or high VCM groups. Rats in the high VCM group were
      either sacrificed on drug or were withdrawn from drug for 4 weeks.
      Ultrastructural analyses of the striatum indicated that synaptic density: 1) was
      significantly decreased in both the low and high VCM groups compared to normal
      controls; 2) was more profoundly decreased in the high VCM group as compared to
      the low VCM group; and 3) recovered to normal following drug withdrawal. Compared
      to controls, the density of asymmetric synapses was reduced by a similar
      magnitude in both the low and high VCM groups, suggesting that this change is a
      result of haloperidol treatment and independent of VCMs. Conversely, the density
      of symmetric synapses was reduced compared to normal, only in the high VCM group,
      suggesting that this change is specifically related to the expression of VCMs. In
      addition, mitochondrial profiles were hypertrophied and less frequent in the high
      VCM group in comparison to controls; size, but not number, recovered following
      drug withdrawal. These results identify distinct ultrastructural correlates of
      chronic haloperidol treatment that are unique to rats that develop VCMs and
      suggest that these ultrastructural features may play a role in the
      pathophysiology of oral dyskinesias in rats.

PMID- 7570357
TI  - Effect of chronic autoimmune nerve growth factor deprivation on sympathetic
      neuroaxonal dystrophy in rats.
AB  - Nerve growth factor (NGF) deficiency has been proposed as a possible pathogenetic
      mechanism underlying the sympathetic autonomic neuropathy which develops in
      clinical and experimental diabetes and aging. To determine if long-term NGF
      deficiency alone would reproduce the distinctive sympathetic neuropathology of
      streptozocin-induced diabetes or aging in rats, nondiabetic animals were deprived
      of NGF for 12 months using an autoimmune paradigm. Neuroaxonal dystrophy (NAD),
      the neuropathologic hallmark of experimental sympathetic diabetic neuropathy and
      aging, was not increased in frequency in prevertebral superior mesenteric or
      paravertebral superior cervical ganglia in comparison to age-matched controls.
      Residual neurons in chronically NGF deprived sympathetic ganglia did not show
      significant atrophy, chromatolysis, active neuronal degeneration or
      intraganglionic debris. Postganglionic noradrenergic axons in ileal mesenteric
      nerves also failed to develop NAD in chronic autoimmune NGF-deprived rats as they
      would have in animals diabetic for the same duration. These results suggest that
      simple, isolated NGF deficiency maintained for long periods of time in
      nondiabetic animals is not sufficient to produce NAD in the pattern of
      experimental rat diabetes and aging.

PMID- 7570356
TI  - Ontogeny of the effect of antipsychotic drug treatment on neurotensin
      concentrations in the rat brain.
AB  - It has been well documented that treatment with haloperidol and other typical
      antipsychotic drugs increase neurotensin (NT) concentrations in the nucleus
      accumbens and caudate nucleus in adult rats. The NT neuronal system has been
      found to undergo distinct age-related changes in the rat brain, and therefore, it
      is of interest to examine the ontogeny of the effects of antipsychotic drug
      treatment on NT concentrations. In order to determine when, or if, antipsychotic
      drug treatment has an effect on NT-containing neurons in the developing rat, rat
      pups received a single dose of haloperidol (2.0 mg/kg, s.c.) or vehicle at 9,14,
      or 20 days after birth. Regional brain NT concentrations were then measured using
      a sensitive and specific radioimmunoassay. Treatment with haloperidol had no
      effect on NT concentrations in any brain region in 10-day-old rat pups. At 15
      days of age, haloperidol significantly increased NT concentrations in the caudate
      nucleus (120% of control, P < 0.05). At 21 days of age, haloperidol increased NT
      concentrations in the caudate nucleus (193% of control, P < 0.001) and nucleus
      accumbens (126% of control, P < 0.005) similar to that seen in adult animals.
      There were no statistically significant gender-related differences found in any
      age or treatment group studied. These findings indicate that there is a specific
      time point during post-natal development when rat brain NT systems become
      responsive to antipsychotic drug administration.

PMID- 7570358
TI  - NMDA receptor expression in the mouse cerebellar cortex.
AB  - A detailed, light microscopic study on the distribution of the N-methyl- D
      aspartate receptor subunit 1 (NMDAR1) was carried out with immunohistochemistry
      and in situ hybridization on the cerebellar cortex of the mouse. With a
      monoclonal antibody, labeling of Purkinje cell bodies varied from intense to
      negative, while heavy dendritic staining was limited to the proximal dendrites
      (unlike the rat, which also had heavily stained distal dendrites). In the
      granular layer, the cell bodies and and the dendritic shafts of Golgi II cells
      were only moderately stained, but very intense labeling was associated with
      granule cell bodies, and with their dendrites and dendritic endings in the
      glomeruli. The mossy and climbing fibers were negative. In situ hybridization
      with a cRNA probe showed levels and spatial distributions of NMDAR1 mRNA
      consistent with the immunolabeling pattern, in that signals were strongest in the
      granular and Purkinje cell layers and relatively low or absent in the molecular
      layer and white matter. The findings are consistent with the hypothesis that
      NMDAR1 may be especially well concentrated at the synaptic target sites of the
      mossy and climbing fibers. In the mouse, NMDAR1 at the parallel fiber sites
      associated with Purkinje cell spiny branchlets may differ from the rat in its
      level of expression or in its molecular configuration.

PMID- 7570359
TI  - Distinct pharmacological regulation of evoked dopamine efflux in the amygdala and
      striatum of the rat in vivo.
AB  - The pharmacological regulation of evoked extracellular dopamine was compared in
      the basolateral amygdaloid nucleus (BAN) and caudate-putamen (CP) of the urethane
      anesthetized rat. The effects of drugs, which alter dopamine uptake, release or
      degradation, were examined. Dopamine efflux was elicited by electrical
      stimulation of ascending dopamine fibers and was monitored by fast-scan cyclic
      voltammetry at Nafion-coated, carbon-fiber microelectrodes. Dopamine uptake
      inhibitors, nomifensine (25 mg/kg) and cocaine (20 mg/kg), and the dopamine
      receptor antagonist, haloperidol (0.5 mg/kg), robustly increased evoked
      extracellular dopamine in the CP. In sharp contrast, these drugs were much less
      effective in the BAN. The relative potencies of the uptake inhibitors varied
      between the two regions. Nomifensine was more potent than cocaine in the CP,
      whereas cocaine was more potent that nomifensine in the BAN. The monoamine
      oxidase inhibitor, pargyline (75 mg/kg), and the catechol-O-methyltransferase
      (COMT) inhibitor, Ro 40-7592 (40 mg/kg), had small or negligible effects in
      either region. No electrochemical evidence was found for the formation of 3
      methoxytyramine, the dopamine metabolite formed by the action of COMT on released
      dopamine, on the time scale of the measurements in control or after
      pharmacological manipulation of the degradative enzymes for dopamine. The
      conclusions reached are: (1) potent mechanisms for uptake and autoreceptor
      inhibition of release, which exist in the CP to tightly control the concentration
      of extracellular dopamine, are considerably weaker in the BAN; (2) the
      extracellular clearance of evoked dopamine in the BAN and CP is the result of
      cellular uptake and not degradation; and (3) these results support the view that
      the pharmacological regulation of extracellular dopamine is regionally distinct
      in the brain.

PMID- 7570360
TI  - Proof of human teratogenicity.

PMID- 7570361
TI  - Proof of human teratogenicity.

PMID- 7570362
TI  - Holoprosencephaly and antiepileptic exposures.

PMID- 7570363
TI  - Acardius acephalus after ovulation induction by clomiphene.

PMID- 7570364
TI  - Exercise at high temperature causes maternal hyperthermia and fetal anomalies in
      rats.
AB  - Hyperthermia is thought to be a teratogen in many animal species and also in
      humans. It has been reported that hyperthermia caused by sauna, hot tub, or fever
      during the early stages of pregnancy is related to an increased risk for neural
      tube defects. During exercise, especially in hot conditions, body temperature can
      also rise to fairly high levels. Thus, we can surmise that hyperthermia induced
      by exercise can also cause fetal malformation. To investigate this hypothesis,
      pregnant rats at 9 days of gestation were divided into four groups. In the first
      group, the animals were made to swim for 30 minutes in water at a temperature of
      40.5 degrees C. In the second group, they were restrained and immersed in water
      for the same time at the same temperature. In the third group, the rats were
      forced to swim in water at 36.0 degrees C. The fourth group were controls. The
      core temperature of the rats was measured during these procedures. On the 18th
      gestational day, fetuses were extracted by cesarean section. The elevation of
      maternal core temperature was significantly greater in the first group than in
      the other groups. In the first group, 69% of fetuses had various external
      anomalies. No anomalies were found in the other groups. Our results show that
      exercise in hot conditions caused the elevation of core temperature and resulted
      in fetal anomalies in rats.

PMID- 7570365
TI  - Symmetrical terminal transverse limb defects: report of a twenty-week fetus.
AB  - A 20-week gestation hydropic Thai fetus is reported who had symmetrical absence
      of each hand and forefoot with persistence of digit-like nubbins on each limb.
      The histologic studies showed there was calcified acellular material in the digit
      like nubbins, consistent with infarcted blood vessels, and cartilaginous
      structures that represented possibly the distal metacarpal articulating surface.
      The red blood cell indices of both parents were consistent with their being
      heterozygous for a hemoglobinopathy, such as alpha-thalassemia, which is common
      in Thais. The infarcted blood vessels could be the result of thrombosis of the
      digital arteries in the fetus due to a hemoglobinopathy such as hemoglobin
      Bart's, just as rabbit fetuses homozygous for brachydactyly have transverse
      terminal digit amputations following digital vessel occlusions due to macrocytic
      anemia. This was the only child with symmetrical absence of the hands and feet
      identified among 123,489 liveborn and stillborn infants surveyed for major
      malformations.

PMID- 7570366
TI  - Developmental toxicity of formate and formic acid in whole embryo culture: a
      comparative study with mouse and rat embryos.
AB  - Acute methanol (MeOH) toxicity in primates is attributed to the conversion of
      MeOH to formate and the resulting acidosis. MeOH has been shown to be
      developmentally toxic in mice and rats both in vivo and in vitro, but rodents
      neither accumulate formate nor develop acidosis after MeOH exposure. To further
      assess the potential human developmental toxicity of MeOH exposure, we evaluated
      the developmental effects of sodium (Na) formate and formic acid in rodent whole
      embryo culture (WEC). Day 9 rat embryos were cultured for 24 or 48 hours and day
      8 mouse embryos were cultured for 24 hours in the presence of Na-formate or
      formic acid. Rat and mouse embryos exposed to either agent for 24 hours exhibited
      a trend toward reduced growth and development and the number of abnormalities
      increased at the higher concentrations. Rat embryos exposed for 48 hours to
      either Na-formate or formic acid showed a trend toward reduced growth and
      development with increasing concentration. Embryo lethality and incidence of
      abnormal embryos were also increased at the higher concentrations. The anomalies
      observed in both species after exposure to either compound were primarily open
      anterior and posterior neuropore with less frequent incidence of rotational
      defects, tail anomalies, enlarged pericardium and delayed heart development.
      Exposure to Na-formate or formic acid for comparable periods of time results in
      comparable degrees of embryotoxicity at concentrations (mMolar) at least 4-fold
      lower than those previously reported for methanol exposure.

PMID- 7570367
TI  - Development of the olfactory nerve: its relationship to the craniofacies.
AB  - Although absence of the olfactory bulbs is a relatively common occurrence seen in
      holoprosencephaly, in Kallman syndrome, and in a number of malformation
      syndromes, the extent to which it determines olfactory nerve development, as well
      as the part it plays in the morphogenesis of the nasal structures, is unknown.
      Cases of arhinencephaly ascertained at autopsy were studied in an effort to
      better understand the relationships between the olfactory nerve, bulb, and
      facies. Based on these studies, it is concluded that both olfactory receptor
      cells and olfactory nerves are present in arhinencephaly, that the olfactory
      nerves did not make contact with the brain in these cases, that the presence of
      olfactory nerves is independent of the severity of the central nervous system
      malformation, and that the shape of the nasal structures is not dependent on the
      presence of the olfactory nerve.

PMID- 7570370
TI  - Exposure of Drosophila melanogaster embryonic cell cultures to 60-Hz sinusoidal
      magnetic fields: assessment of potential teratogenic effects.
AB  - There is considerable concern about potential detrimental health effects
      associated with exposure to environmentally relevant magnetic fields. One
      specific concern relates to potential effects of magnetic field (MF) exposure on
      reproduction and development. Consequently, an in vitro teratogenesis
      (developmental toxicity) assay employing embryonic Drosophila cells has been used
      to determine whether exposure to a 60-Hz MF of 100 microT for 16-18 hr is itself
      teratogenic and whether such an exposure could potentiate the teratogenic
      response induced by a chemical teratogen (developmental toxicant). The results
      demonstrated that (1) MF exposure alone did not induce a teratogenic response,
      whether the MF was oriented parallel or perpendicular to the plane of the culture
      dishes; and (2) MF exposure did not alter the teratogenic response induced by
      optimal or suboptimal concentrations of three chemical teratogens (retinoic acid,
      hydroxyurea, and cadmium). Furthermore, in additional studies, Drosophila embryos
      were exposed to 60-Hz MFs of 10 and 100 microT for 24 hr or for their entire
      development time (i.e., until adult ecolsion, about 10 days). Results
      demonstrated that MF exposure did not produce an increase in developmental
      abnormalities over those observed in unexposed controls.

PMID- 7570368
TI  - Placental transfer and developmental effects of 9-cis retinoic acid in mice.
AB  - 9-cis retinoic acid (RA) is a naturally occurring isomer of all-trans RA. While
      both isomers can bind with high affinity and activate RA receptors, only 9-cis RA
      is the specific ligand for the retinoid X receptors. 9-cis RA has also been shown
      to be much more potent than all-trans RA in inducing digit duplication in the
      chick embryo wing bud. To gain further insight into its mechanisms, here we
      investigated the teratogenic activity in pregnant mice of 9-cis RA and compared
      it with those of all-trans RA and 13-cis RA. Using frequency and severity of limb
      reduction defects as well as palatal clefts in the resultant fetuses as
      indicators, we found that orally administered 9-cis RA was one-half as potent a
      teratogen as all-trans RA. That 9-cis RA was intrinsically less active than all
      trans RA was deduced by comparing the inhibitory activities of the two retinoids
      in the limb bud mesenchymal cell micromass cultures using chondrogenesis as an
      end-point. Since placental transfer of cis isomers of RA is generally poor, we
      monitored the identities and amounts of retinoids in the embryo after
      administration of 9-cis RA to the mother. We found that 9-cis RA undergoes
      extensive metabolism and isomerization during absorption resulting in a number of
      metabolites in the maternal circulation within 30 min after administration.
      Although some of these metabolites remain to be identified, the most abundant RA
      isomers in the plasma coeluted with 13-cis RA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570369
TI  - Cellular adaptation to chronic cadmium exposure: intracellular localization of
      metallothionein protein in human trophoblast cells (JAr).
AB  - Trophoblast cells are the first embryonic cells that modulate the transfer of a
      variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal
      to the fetal circulation in the human placenta. Human placental exposure to the
      toxic metal, cadmium (Cd) results in a decrease in the production of human
      chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of
      zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to
      adapt to exposure to the toxic metal Cd has been considered crucial. In this
      study, the expression and intracellular localization of metallothionein (MT), a
      small molecular weight, metal binding protein, was examined in trophoblast cells
      (JAr) grown in normal media and in cells exposed chronically (6 months) to 2
      microM CdCl2. Conventional and confocal fluorescence microscopy were used to
      examine the intracellular localization of MT protein in control cells and cells
      grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily
      perinuclear with low level, punctate expression in the cytosol. Following both
      chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3
      fold in both chronic and acute exposures) and the protein was now concentrated
      inside the nucleus with a lacy, cytoskeletal pattern of expression in the
      cytosol. To determine if the nuclear accumulation of MT protein was dependent on
      new protein synthesis, control cells were exposed to CdCl2 (2 microM) and
      cycloheximide (2 micrograms/. ml) for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570372
TI  - Back at the table. Medicare debate is reminiscent of health-system reform battle.
AB  - The eminent philosopher Yogi Berra once said, "It's like deja vu all over again."
      Those who followed last year's debate on health-system reform may indeed feel
      they are experiencing deja vu when Congress launches into its much anticipated
      debate over how to reform Medicare, cut spending, and save the health-care
      program for the elderly from certain bankruptcy.

PMID- 7570371
TI  - Have we got a deal for you, doc. Small towns recruiting big time to lure
      physicians to rural Texas.
AB  - Ask most folks if they would trade the crime, high taxes, traffic nightmares, and
      general hassle of big cities for the pastoral setting of small-town life, and
      their first question may be what time the moving van arrives. Life in a small
      town can be peaceful, quiet, and relaxing: just the tonic for the headaches of
      modern urban life. Then reality in the form of illness intrudes, and the services
      of a doctor are needed. Unfortunately, in many rural areas of Texas, one may not
      be available.

PMID- 7570373
TI  - The road to recovery. New law removes one barrier to rehabilitation for impaired
      physicians.
AB  - In its handling of impaired physicians since the late '80s, the Texas State Board
      of Medical Examiners (TSBME) seemed limited to wielding a proverbial stick. But
      thanks to a new Texas law, TSBME also can now hold out a carrot to impaired
      physicians who will report themselves to the board.

PMID- 7570374
TI  - The write stuff. Simple guidelines can help you write and design effective
      patient education materials.
AB  - Most of the time and energy that go into patient education focus on the brief
      encounter between a doctor and patient in the physician's office. Although face
      to-face interaction is indispensable in educating patients about their
      conditions, it also poses many problems. The stressful nature of the situation
      may cause patients to forget to ask questions or forget what they are told, and
      they may not get enough information to satisfy their needs and curiosities.

PMID- 7570376
TI  - Room service with a smile ... and a stethoscope.

PMID- 7570377
TI  - Board certification denounced as sole screening mechanism.

PMID- 7570378
TI  - Physicians should take note of Governor Bush's veto.

PMID- 7570375
TI  - Market-driven reform: what must change and what must not.

PMID- 7570379
TI  - Double-barreled assault.
AB  - When voters in Wichita Falls went to the polls in early May, they thought they
      were casting ballots to determine if smoking in public places would be regulated
      in their community. In reality, their decision likely determined the fate of
      antismoking efforts throughout Texas. In the 74th Texas Legislature, the tobacco
      industry launched a two-pronged attack it hoped would deal a devastating blow to
      local communities' attempts to regulate public smoking. The first prong was a
      legislative attack on the ability of cities to pass antismoking regulations. The
      second was an attempt to actually roll back a tough local antismoking ordinance
      at the polls, thereby demonstrating lack of public support for such ordinances.

PMID- 7570380
TI  - Medical savings accounts.
AB  - Let's take a walk down memory lane. Think real hard. Remember the good old days
      when patients came to your office, you diagnosed their illnesses, and you
      prescribed courses of treatment that your training and experience told you were
      necessary? Either patients paid you directly or you billed their insurance
      companies. And, if you decided hospitalization was needed, your patients stayed
      there until you decided they were well enough to go home. You and your patients
      made the necessary decisions.

PMID- 7570383
TI  - Sick jokes. Doctor, it hurts when I do this. Then don't do that.

PMID- 7570384
TI  - Women in medicine.
AB  - It happened at Yale, Harvard, and Johns Hopkins for the first time in the
      histories of those prestigious medical schools last fall. Now the trend has
      reached Texas. This September, Women in Medicine Month, women will outnumber men
      in the first-year class at The University of Texas-Houston Medical School. As of
      late July, 107 women and 91 men had been accepted to attend the medical school at
      UT-Houston Health Science Center this fall. The number of female faculty at the
      health science center has increased from 128 in 1989 to 253 in 1995. So what
      makes this particular institution so female friendly?

PMID- 7570382
TI  - Getting organized. Pros and cons of business structures for medical practice.

PMID- 7570385
TI  - Physician strategies for the 21st century.

PMID- 7570387
TI  - Who is really benefiting from managed care?

PMID- 7570386
TI  - Ethnic differences in causes of infant mortality: Texas births, 1989 through
      1991.
AB  - The mortality rate of African-American infants in Texas is about twice those of
      Anglo and Hispanic infants, due at least partly to their increased risk of
      preterm and low-weight birth. We examined the underlying causes of infant deaths
      from 1989 through 1991 for specific causes that accounted for the racial
      difference and for those that were associated with those adverse pregnancy
      outcomes. The overall infant mortality rate was 8.27 per 1000 live births (6.80
      for Anglo, 7.72 for Hispanic, and 15.32 for African-American infants). About 37%
      of all infant deaths (but 48% of African-American deaths) were associated with
      adverse pregnancy outcomes; excluding these deaths reduced the overall rate to
      5.20 per 1000 (4.59 for Anglo, 5.03 for Hispanic, and 8.05 for African-American
      infants). Accordingly, reducing adverse pregnancy outcomes in African-American
      women will reduce but not resolve the discrepancy in racial infant mortality
      rates. Infant mortality rates for 30 of the top 59 causes of death were at least
      1.5 times higher in African-American than in Anglo and Hispanic infants, while a
      comparable excess in Hispanic infants was noted only for anencephaly; Anglo
      infants did not have an excessive mortality rate for any of the 59 causes.
      Reduction of the racial infant mortality rate discrepancy in Texas will require
      clarification and correction of factors that place pregnancies of African
      American women at increased risk for adverse pregnancy outcomes and those that
      place their infants at increased risk for death from a wide range of causes.

PMID- 7570381
TI  - From collegial to codified. The evolution of modern peer review.
AB  - Physician peer review a quarter of a century ago was different than peer review
      today. Twenty-five years ago, peer review was conducted so physicians could learn
      from each other. But quality assurance and risk management programs have led to
      an adversarial review of physicians' practices, changing the nature of peer
      review. Physicians practicing today should understand how this change happened
      and how to cope with the results.

PMID- 7570388
TI  - Legal issues for nurses. Consent & disclosure of medical treatment for minors:
      new issues for generation X and beyond. Part II.

PMID- 7570389
TI  - Protecting and educating your patients. Liquid medication dosing devices and
      syringes.

PMID- 7570390
TI  - Legal issues for nurses. Disciplinary action by the Texas BNE. Part I.

PMID- 7570391
TI  - HMOs investing in tobacco industry represents conflict of values.

PMID- 7570392
TI  - Women's health nurses pave the way.

PMID- 7570393
TI  - Specialists without spirit: limitations of the mechanistic biomedical model.
AB  - This paper examines the origin and the development of the mechanistic model of
      the human body and health in terms of Max Weber's theory of rationalization. It
      is argued that the development of Western scientific medicine is a part of the
      broad process of rationalization that began in sixteenth century Europe as a
      result of the Reformation. The development of the mechanistic view of the human
      body in Western medicine is consistent with the ideas of calculability,
      predictability, and control-the major tenets of the process of rationalization as
      described by Weber. In recent years, however, the limitations of the mechanistic
      model have been the topic of many discussions. George Engel, a leading advocate
      of general systems theory, is one of the leading proponents of a new medical
      model which includes the general quality of life, clean environment, and
      psychological, or spiritual stability of life. The paper concludes with
      consideration of the potential of Engel's proposed new model in the context of
      the current state of rationalization in modern industrialized society.

PMID- 7570394
TI  - To test or not to test: a clinical dilemma.
AB  - This paper argues that clinicians are sometimes justified in not testing
      diagnoses or in not subjecting them to a full battery of tests. In deciding
      whether to conduct a test, a clinician may consider and weigh several different
      factors, including her confidence in her initial diagnosis, the specificity and
      sensitivity of the test, the consequences of making a false diagnosis, the pain,
      harm, and inconvenience caused by the test, and the costs of the test to the
      patient and society. This view suggests that diagnoses are fundamentally
      different from scientific hypotheses in that they are not always subjected to the
      same evidential standards.

PMID- 7570395
TI  - Environmental risks: scientific concepts and social perception.
AB  - Using the example of air pollution, I criticize a restricted utilitarian view of
      environmental risks. It is likely that damage to health due to environmental
      pollution in Western countries is relatively modest in quantitative terms
      (especially when considering cancer and comparing such damage to the effects of
      some life-style exposures). However, a strictly quantitative approach, which
      ranks priorities according to the burden of disease attributable to single
      causes, is questionable because it does not consider such aspects as inequalities
      in the distribution of risks. Secondly, the ability of epidemiological research
      to identify some health effects is limited. Third, the environment has symbolic
      and aesthetic components that overcome a strict evaluation of damage based on the
      impairment of human health. It is not acceptable that priorities be set just
      balancing the burden of disease caused by pollution in the environment against
      economic constraints. As an example of a computation that inherently includes
      economic analysis, I refer to the proposal of an estimator of mortality in coal
      mining, i.e., a rate which puts deaths in the numerator and tons of coal
      extracted in the denominator. According to this estimator, mortality due to
      accidents decreased from 1.15 to 0.42 in the period 1950-1970 in the United
      States, for each million tons of coal extracted. However, considering the steep
      decline in the workforce in the same period, the traditional mortality rate
      (deaths over persons-time) actually increased. The proposal of a measure of
      mortality based on the amount of coal extracted is just one example of the
      attempts to influence decisions by including an economic element (productivity)
      in risk assessment. This paper has three purposes: One, to describe empirical
      research concerning the health effects of environmental pollutants; two, to
      discuss the scientific principles and methods used in the identification of
      environmental hazards; and three, to critically discuss some of the ethical
      principles which are applied in medicine and in the assessment and management of
      risk.

PMID- 7570397
TI  - The legitimacy of clinical knowledge: towards a medical epistemology embracing
      the art of medicine.
AB  - The traditional medical epistemology, resting on a biomedical paradigmatic
      monopoly, fails to display an adequate representation of medical knowledge.
      Clinical knowledge, including the complexities of human interaction, is not
      available for inquiry by means of biomedical approaches, and consequently is
      denied legitimacy within a scientific context. A gap results between medical
      research and clinical practice. Theories of knowledge, especially the concept of
      tacit knowing, seem suitable for description and discussion of clinical
      knowledge, commonly denoted "the art of medicine." A metaposition allows for
      inquiry of clinical knowledge, inviting an expansion of the traditional medical
      epistemology, provided that relevant criteria for scientific knowledge within
      this field are developed and applied. The consequences of such approaches are
      discussed.

PMID- 7570396
TI  - Placebo effect and randomized clinical trials.
AB  - The achievement of optimal therapeutic results presupposes the use of appropriate
      treatment combined with maximal utilization of placebo effects. These aims may
      sometimes be difficult to satisfy in randomized clinical trials (RCTs). The
      question thus arises whether there is a conflict between the goals of therapy and
      those of experimental research; and if so, to what extent, and how is it handled
      in practice by clinicians and researchers. Various ethical problems have been
      discussed in several reports connected with RCTs. But we have found no discussion
      concerning the conflict between obtaining informed consent and promoting optimal
      placebo effects. Information about RCTs can be given in various ways. Sometimes
      appropriate information about RCTs to patients involves non-optimal utilization
      of placebo effects. This gives rise to ethical and methodological problems, which
      are discussed in this article.

PMID- 7570398
TI  - A Kantian argument in favor of unimpeded access to health care.
AB  - The principle that everybody should have access to essential health care is in
      conflict with the notion that property rights should be respected. The Kantian
      doctrine of rights is explored in order to solve this conflict. Kant's notion of
      a legislative will is explained and used to show the inherent limits of the legal
      terms "property" and "ownership" (it can refer only to things external to
      subjects and to possible objects of choice). What is internal to the subject is
      outside of the realm of the legislative will. A law excluding those unable to pay
      from access to essential health care would not be just. A law granting that
      access would be just.

PMID- 7570399
TI  - Kant, health care and justification.
AB  - An argument based on Kant for access to health-care for all is a most helpful
      addition to prior discussions. My paper argues that while such a point of view is
      helpful it fails to be persuasive. What is needed, in addition to a notion of the
      legislative will, is a viewpoint of community which sees justice as originating
      not merely from considerations of reason alone but from a notion of community and
      from a framework of common human experiences and capabilities.

PMID- 7570400
TI  - Neonatal screening for cystic fibrosis.

PMID- 7570401
TI  - Pulmonary arteriovenous malformations.

PMID- 7570404
TI  - Embolisation of pulmonary arteriovenous malformations: results and follow up in
      32 patients.
AB  - BACKGROUND: Pulmonary arteriovenous malformations may cause a number of
      complications when left untreated. Embolisation of the feeding vessels is a
      relatively new approach and information concerning its efficacy and long term
      results is scarce. METHODS: Pulmonary arteriovenous malformations with feeding
      arteries of > 3 mm were treated by embolisation. Right to left shunt fraction and
      arterial oxygen pressure breathing air (PaO2) were measured before and after
      treatment. Six monthly measurement of shunt fraction was used for follow up.
      RESULTS: In 32 patients 92 pulmonary arteriovenous malformations were treated by
      coil embolisation. Mean shunt fraction decreased from 16.6% to 7.4% and PaO2
      increased from 9.6 kPa to 11.5 kPa. Treatment was incomplete in two patients, one
      of whom was subsequently treated surgically. Serious complications occurred in
      one patient. Recanalisation of embolised vessels occurred in two cases after 22
      and 28 months, respectively. Mean period of follow up was 25 months. CONCLUSIONS:
      Embolisation is a safe and efficacious treatment for most pulmonary arteriovenous
      malformations. Long term studies are necessary to determine the risk of
      recanalisation.

PMID- 7570403
TI  - Long term prognosis of patients with cystic fibrosis in relation to early
      detection by neonatal screening and treatment in a cystic fibrosis centre.
AB  - BACKGROUND: A study was undertaken to evaluate whether an early diagnosis by
      neonatal screening may improve the long term prognosis of patients with cystic
      fibrosis and to assess the influence of expert management started immediately
      after the diagnosis. METHODS: Comparative clinical follow up in three birth
      cohorts of patients with cystic fibrosis was performed at the Cystic Fibrosis
      centre in Groningen in close collaboration with paediatricians in general
      hospitals in the north-eastern part of the Netherlands. The first birth cohort (n
      = 19) was detected by screening and the two other cohorts were detected
      clinically, one (n = 30) consisting of patients born during the screening
      programme and the other (n = 32) of patients born during the six years
      immediately after the screening programme ended. The total number of patients in
      the three birth cohorts included all patients with cystic fibrosis born in this
      area during a 12 year period. Cumulative survival rates and the variation with
      time of lung function, the levels of immunoglobulins, and growth patterns were
      used as main outcome measures. RESULTS: Patients born during the screening
      programme but detected clinically appeared to have a reduced life expectancy
      compared with patients detected by screening. The patients detected by screening
      showed less deterioration in lung function (annual decrease 1.2% of FEV1 % pred),
      a smaller increase in immunoglobulin levels, and minimal catch-up growth compared
      with an annual decrease of 3.25% of FEV1 % pred in the non-screened birth cohort
      of the same age, a higher rise in immunoglobulins leading to increased levels at
      the end of the observation period, and catch-up growth for weight as well as
      height. Differences between patients treated in a cystic fibrosis centre and
      those not referred to a specialist centre were smaller but similar, in favour of
      treatment at a cystic fibrosis clinic. CONCLUSIONS: Expert management started
      immediately after an early diagnosis of cystic fibrosis by neonatal screening
      results in important beneficial effects on the outcome and clinical course of the
      condition. The institution of very early treatment may be critical for the
      outcome and long term prognosis for most patients with cystic fibrosis. Neonatal
      screening programmes for cystic fibrosis should be introduced more widely.

PMID- 7570402
TI  - Molecular diagnosis of tuberculosis: the need for new diagnostic tools.

PMID- 7570405
TI  - Validation of an asthma quality of life diary in a clinical trial.
AB  - BACKGROUND: Quality of life (QOL) is commonly measured in asthma clinical trials
      by a questionnaire given before and after treatment. A structured asthma QOL
      daily diary provides more restricted information but on a daily basis. The
      validity and use of such a QOL diary was examined in a clinical trial in which
      two asthma treatments were compared. METHODS: The effects of low dose inhaled
      steroid (400 micrograms beclomethasone dipropionate, BDP) combined with the long
      acting beta 2 agonist salmeterol (100 micrograms) (n = 220) was compared with
      high dose inhaled steroid (1000 micrograms BDP) (n = 206) in asthmatic
      outpatients in a double blind, parallel group study. Outcome measures consisted
      of a combined diary for peak expiratory flow (PEF) rate, symptoms, and problems,
      and an asthma-specific QOL questionnaire, the Living with Asthma Questionnaire.
      RESULTS: The QOL diary correlated with the QOL questionnaire for both cross
      sectional and longitudinal assessments. Cross sectional correlations with PEF
      were higher for the QOL questionnaire than the QOL diary, but longitudinal
      correlations with PEF were higher for the diary than the questionnaire. Treatment
      with low dose steroid/salmeterol compared with high dose steroid produced better
      lung function, better QOL as measured by diary, and reduced night time wakenings,
      but treatment differences were not obtained with the QOL questionnaire nor for
      daytime symptoms. Diary assessed QOL was a better predictor of low PEF than diary
      assessed symptoms. Compliance with diary completion was good but there were floor
      or ceiling effects in the QOL diary records of about 25% of patients.
      CONCLUSIONS: Structured QOL diaries are valid instruments that appear to be more
      responsive to longitudinal change in clinical trials than a QOL questionnaire,
      but QOL questionnaires provide a more sensitive cross sectional measure of
      disease severity. Floor and ceiling effects are found in some patients' QOL
      diaries which limit their usefulness. QOL diary problem events occur during the
      troughs of a peak flow graph, while symptoms are more widely distributed with
      respect to peak flow.

PMID- 7570406
TI  - Randomised trial of an asthma self-management programme for adults.
AB  - BACKGROUND: A hospital based, community service asthma education programme for
      adults to improve asthma knowledge, promote compliance with medication, and
      reduce morbidity was evaluated. METHODS: The programme was evaluated using a
      randomised experimental and control group design with repeated measurements over
      12 months. A volunteer community sample of 192 respondents was recruited of whom
      116 satisfied the inclusion criteria. At the 12 month follow up some data were
      obtained for all subjects. Intervention subjects attended four 2.5 hour education
      sessions at weekly intervals. An asthma knowledge questionnaire was administered
      and compliance was assessed from diary records. Morbidity was assessed
      retrospectively by questionnaire, prospectively by diary, and objectively by
      spirometry and serial peak expiratory flow rate monitoring. The adequacy of
      medical treatment was also assessed. Data were collected at baseline, immediately
      after the intervention, and at three, six, nine, and 12 months after
      intervention. RESULTS: Improvements occurred in knowledge and compliance in the
      intervention group but the impact on morbidity was modest; this was due, at least
      in part, to the inadequacy of medical treatment. CONCLUSIONS: Treatment of asthma
      should be reviewed and optimised in conjunction with self-management programmes
      in order to improve health outcomes.

PMID- 7570408
TI  - Factors affecting total and "respirable" dose delivered by a salbutamol metered
      dose inhaler.
AB  - BACKGROUND: Many factors contribute to the high variability of doses delivered to
      the lungs of patients using metered dose inhalers (MDIs). Relatively little
      attention has been paid to the contribution to this variability of the way in
      which the MDI is handled before the inhalation manoeuvre. Instruction leaflets
      often recommend procedures at odds with those used for in vitro testing of the
      device. The standard protocol for in vitro assessment of salbutamol MDIs involves
      shaking the MDI vigorously for 30 seconds and wasting the first two actuations.
      Subsequent actuations are introduced into the testing device at five second
      intervals. Patient instructions do not include a recommendation to waste the
      first two actuations and recommend a delay of one minute between actuations. A
      series of experiments was performed to determine whether such differences might
      be important. METHODS: The total and "respirable" doses delivered by a salbutamol
      MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a
      multistage liquid impinger. The quantity of drug deposited on each stage was
      measured by an ultraviolet spectrophotometric method. The effect on the delivered
      dose of not shaking the canister, not wasting the first two doses, waiting 30
      seconds between actuations, and using multiple rapid actuations was assessed by
      comparing the results with those obtained using the standard in vitro testing
      protocol. RESULTS: Compared with a standard protocol, it was found that not
      shaking the MDI before use reduced the total and "respirable" dose by 25.5% and
      35.7%, respectively. The dose delivered when actuating the MDI at 30 second
      intervals was no different from that when intervals was no different from that
      when intervals of five seconds were used. Two actuations separated by one second
      had no effect on the total dose but reduced the "respirable" dose by 15.8%, while
      four rapid actuations reduced the total and "respirable" doses by 8.2% and 18.2%,
      respectively. Storing the MDI stem down reduced the total and "respirable" dose
      delivered in the first actuation by 25.0% and 23.3% despite shaking the MDI
      before use. CONCLUSIONS: MDIs containing drug in suspension must be shaken before
      use to resuspend the drug contained in the MDI, but shaking does not alter the
      composition of the suspension in the metering chamber and hence the dose in the
      first actuation remains low. Very rapid actuations can reduce the dose delivered
      per actuation, but salbutamol MDIs can be actuated immediately after a 10 second
      breath holding pause without affecting the dose delivered.

PMID- 7570407
TI  - Microbial inciters of acute asthma in urban Nigerian children.
AB  - BACKGROUND: In tropical Africa the role of microbial agents of acute respiratory
      infections in acute exacerbations of bronchial asthma remains largely unexplored.
      However, empirical antibacterial therapy is frequently initiated in moderate to
      severe cases of acute asthma with symptoms of acute respiratory infection. A
      study was set up to determine how often acute respiratory infection is associated
      with acute asthma, to identify the associated pathogens, and to proffer
      appropriate therapeutic suggestions. METHODS: Over a 16 month period, 86 episodes
      of acute asthma were studied for clinical and laboratory features of acute
      respiratory infection at the University College Hospital (UCH), Ibadan.
      Virological diagnosis was based on immunofluorescence studies of nasopharyngeal
      aspirates and/or serological tests using the microtitre complement fixation
      technique. Throat swabs and blood were cultured for bacterial agents. RESULTS: Of
      the 64 cases who presented with rhinorrhoea, 51 (79.7%) were pyrexial (T > or =
      37.6 degrees C). Inflammatory changes (frequently interstitial streakiness) were
      identified in 10 (19.6%) of the 51 chest radiographs; only two of these had lobar
      shadowing. Significant bacterial isolates were made in only three (3.5%) of the
      throat swabs and two (2.4%) of the blood cultures from the 86 cases; none had
      clinical septicaemia. On the other hand, 55 viral agents were identified from 39
      (53%) of the 74 subjects studied; 16 (41.0%) had dual viral identifications.
      Respiratory syncytial virus (RSV) accounted for 20 (36.4%) identifications,
      parainfluenza virus (PIV) type 3 for 15 (27.3%), and influenza type A (Flu A) for
      12 (21.8%). Viral identifications were significantly higher in infants and
      preschool subjects (< 5 years) and in those presenting with either rhinorrhoea or
      pyrexia. CONCLUSIONS: The results of this study underscore the importance of
      viral upper respiratory infections in asthma exacerbations in a tropical setting.
      The paucity of clinical and investigative features of bacterial acute respiratory
      infection suggests that there is little rationale for routine antibiotic cover in
      children with acute exacerbations of asthma in the tropics.

PMID- 7570410
TI  - Non-invasive mechanical ventilation in acute respiratory failure due to chronic
      obstructive pulmonary disease: correlates for success.
AB  - BACKGROUND: Non-invasive mechanical ventilation is increasingly used in the
      treatment of acute respiratory failure in patients with chronic obstructive
      pulmonary disease (COPD). The aim of this study was to identify simple parameters
      to predict the success of this technique. METHODS: Fifty nine episodes of acute
      respiratory failure in 47 patients with COPD treated with non-invasive mechanical
      ventilation were analysed, considering each one as successful (78%) or
      unsuccessful (22%) according to survival and to the need for endotracheal
      intubation. RESULTS: Pneumonia was the cause of acute respiratory failure in 38%
      of the unsuccessful episodes but only in 9% of the successful ones. Success with
      non-invasive mechanical ventilation was associated with less severely abnormal
      baseline clinical and functional parameters, and with less severe levels of
      acidosis assessed during an initial trial of non-invasive mechanical ventilation.
      CONCLUSIONS: The severity of the episode of acute respiratory failure as assessed
      by clinical and functional compromise, and the level of acidosis and hypercapnia
      during an initial trial of non-invasive mechanical ventilation, have an influence
      on the likelihood for success with non-invasive mechanical ventilation and may
      prove to be useful in deciding whether to continue with this treatment.

PMID- 7570412
TI  - Effect of ambient levels of smoke and sulphur dioxide on the health of a national
      sample of 23 year old subjects in 1981.
AB  - BACKGROUND: There is concern that, despite the fall in air pollution levels since
      the 1950s, there may still be adverse effects at current levels. A study was
      carried out to investigate the association between air pollution and respiratory
      symptoms in 23 year old subjects in 1981. METHODS: Data on cough, phlegm, and
      wheeze were available on 11,552 members of the 1958 national birth cohort.
      Counties in the UK were ranked by annual average level of black smoke and sulphur
      dioxide (SO2), and then divided into five groups. The subject's county of
      residence determined their categorisation of pollution exposure. The association
      between air pollution exposure and respiratory symptoms was examined by logistic
      regression, adjusting for social class, sex, and smoking. RESULTS: The ranges of
      the air pollution groups were 2.0-13.0, 13.1-18.7, 19.6-20.8, 21.0-25.8, and 26.1
      55.1 micrograms/m3 for black smoke, and 7.0-36.4, 36.7-42.7, 43.0-50.5, 52.0
      59.3, and 60.9-87.7 micrograms/m3 for SO2. The overall prevalences of cough,
      phlegm, wheezing since age 16, and wheezing in the past year were 13.3%, 10.3%,
      9.4%, and 4.4%, respectively. Phlegm symptoms increased with increasing smoke
      levels with evidence of a plateau. Cough and wheeze were not associated with
      black smoke; no symptom was associated with SO2. In the subgroup with wheeze at
      ages 16-23 there was no effect of smoke level on phlegm. CONCLUSIONS: Low ambient
      levels of black smoke were associated with decreased prevalence of phlegm
      symptoms in young adults in the UK in 1981. The effect was evident below the
      current EC guideline of 34-51 micrograms/m3 annual black smoke. In 1991 the
      annual mean smoke level for each county ranged from 3.4 to 26.5 micrograms/m3,
      spanning all but the last exposure group used here. This is consistent with the
      existence of adverse and possibly chronic effects at current levels.

PMID- 7570411
TI  - Changes in symptoms, peak expiratory flow, and sputum flora during treatment with
      antibiotics of exacerbations in patients with chronic obstructive pulmonary
      disease in general practice.
AB  - BACKGROUND: Bacterial infections of the lower airways during an exacerbation in
      patients with asthma or chronic obstructive pulmonary disease (COPD) may be the
      cause of an exacerbation or the consequence of a viral infection or an increase
      in airways limitation. To determine whether bacterial infection is an important
      component in the pathogenesis of an exacerbation, the effects of antimicrobial
      treatment must be studied. METHODS: Patients with asthma or COPD seen in general
      practice were studied in a double blind randomised manner to investigate whether
      the antimicrobial drugs amoxicillin (500 mg three times daily), cotrimoxazole
      (960 mg twice daily), or a placebo, each when added to a short course of oral
      corticosteroids, can accelerate recovery from exacerbations. Patients were
      instructed to contact their own physician early in the morning when complaints of
      increased shortness of breath, wheezing, or exacerbations of cough with or
      without sputum production occurred. Treatment effects were evaluated over the
      next 14 days by studying symptom scores (wheeze, dyspnoea, cough with and without
      mucus production, and awakening with dyspnoea), peak expiratory flow values (PEF,
      expressed as % predicted), and sublingual temperature. Bacteriological study of
      the sputum was made at the onset of an exacerbation and 7, 21 and 35 days
      afterwards. RESULTS: Of 195 patients enrolled 71 (36%) contacted their physician
      for symptoms of an exacerbation. Symptoms improved in all three groups,
      improvements ranging from 0.54 to 0.75 points per day on a four point scale. PEF%
      predicted showed improvements in the three groups after the exacerbation, ranging
      from 0.34% to 0.78% predicted per day, finally returning to baseline values.
      Sublingual temperature did not change. Six of 71 patients consulted their
      physician because of a relapse between four and 24 days after the start of
      treatment. In only two of the 50 sputum samples, collected during an
      exacerbation, and which contained > or = 10(5) bacteria in culture sensitive to
      the chosen antibiotic given, did any benefit from antimicrobial treatment occur.
      During the recovery period sputum purulence improved irrespective of antibiotic
      treatment. CONCLUSIONS: Antibiotics given with a short course of oral
      prednisolone during an exacerbation do not accelerate recovery as measured by
      changes in peak flow and symptom scores in ambulatory patients with mild to
      moderate asthma or COPD when treated by their general practitioners. Moreover,
      antibiotics do not reduce the number of relapses after treating an exacerbation.

PMID- 7570409
TI  - Efficacy of inhaled salmeterol in the management of smokers with chronic
      obstructive pulmonary disease: a single centre randomised, double blind, placebo
      controlled, crossover study.
AB  - BACKGROUND: The acute response to bronchodilators in patients with chronic
      obstructive pulmonary disease (COPD) is modest; it has, however, been suggested
      that these patients may benefit from long term treatment. METHODS: To investigate
      the efficacy of salmeterol in smokers with moderate to severe COPD a double
      blind, randomised, crossover comparison was performed between salmeterol (50
      micrograms twice daily) and placebo in 63 patients with stable COPD (mean age 65
      years). Prior to inclusion, all patients had a forced expiratory volume in one
      second (FEV1) of < 60% of predicted and an improvement in FEV1 of < 15% following
      400 micrograms inhaled salbutamol. Patients received four weeks of therapy with
      each of the treatment regimens. Assessment of efficacy was made with recording of
      morning and evening peak expiratory flow rates (PEF), respiratory symptoms, and
      use of rescue salbutamol. FEV1 was measured before and after nebulised salbutamol
      prior to randomisation and at the end of each treatment period. RESULTS: Morning
      PEF values were higher during the salmeterol than during the placebo period,
      although the mean treatment difference was small (12 l/min (95% confidence limits
      6 to 17)). No difference in mean evening PEF values was found. Diurnal variation
      in PEF, assessed as the difference between the morning PEF and that of the
      previous evening, was more pronounced during the placebo than during the
      salmeterol period. The mean spirometric values (including reversibility in FEV1)
      obtained at the end of the two treatment periods were similar. Compared with
      placebo, treatment with salmeterol was associated with lower daytime and night
      time symptom scores and less use of rescue salbutamol both during the day and the
      night. The patients rated the treatment with salmeterol better than treatment
      with placebo. CONCLUSIONS: This study shows that, compared with placebo,
      treatment with salmeterol produces an improvement in respiratory symptoms and
      morning PEF values in patients with moderate to severe COPD. Treatment with long
      acting beta agonists may therefore result in an improvement in functional status,
      even in patients suffering from apparently nonreversible obstructive pulmonary
      disease.

PMID- 7570413
TI  - Exposure to cobalt chromium dust and lung disorders in dental technicians.
AB  - BACKGROUND: Dental technician's pneumoconiosis is a dust-induced fibrotic lung
      disease of fairly recent origin. This study was carried out to estimate its
      occurrence in Sweden. METHODS: Thirty seven dental technicians in central and
      south eastern Sweden with at least five years of exposure to dust from cobalt
      chromium molybdenum (CoCrMo) alloys, identified by postal survey, agreed to
      undergo chest radiography and assessment of lung function and exposure to
      inorganic dust. RESULTS: Six subjects (16%; 95% confidence interval 6% to 23%)
      showed radiological evidence of dental technician's pneumoconiosis. The lung
      function of the study group was reduced compared with historical reference
      material. With local exhaust ventilation dust levels were generally low, whereas
      in dental laboratories without such equipment high levels of dust, particularly
      cobalt, were found. CONCLUSIONS: Pneumoconiosis may result from exposure to
      inorganic dust in the manufacturing of CoCrMo-based dental constructions. It is
      possible to reduce this hazard substantially by local exhaust ventilation.

PMID- 7570414
TI  - Ethnic origin and lung function of infants born prematurely.
AB  - BACKGROUND: Ethnic origin has an important influence on the lung function of
      adults and young children but its effect during infancy, particularly following
      premature delivery, is unclear. METHODS: The results from infants of pure Afro
      Caribbean (subjects) and pure Caucasian (controls) descent, all of whom were born
      prematurely (median gestational age 28 weeks), were compared. Fifty subjects were
      each retrospectively matched with a control for gestational age, sex, and
      requirement for neonatal ventilation. Lung function measurements were performed
      at similar postnatal ages in each pair. The median postnatal ages of the two
      groups at the time of study was seven and eight months, respectively. Lung
      function was assessed by measurement of functional residual capacity (FRC) by a
      helium gas dilution technique and plethysmographic measurement of thoracic gas
      volume (TGV) and airways resistance (Raw), from which specific conductance (sGaw)
      was calculated. RESULTS: No differences were found between the subjects and
      controls regarding FRC or TGV, but Raw was higher and sGaw lower in the subjects.
      The mean Raw of the subjects was 50.3 cm H2O/1/s and of the controls was 44.1 cm
      H2O/1/s (95% confidence intervals of the difference 1.5 to 10.9). CONCLUSIONS:
      Prematurely born infants of Afro-Caribbean origin have more severe lung function
      abnormalities at approximately 7-8 months of age than those of Caucasian origin.
      This merits further investigation.

PMID- 7570415
TI  - Changes to alveolar macrophage phenotype in HIV infected individuals with normal
      CD4 counts and no respiratory disease.
AB  - BACKGROUND: It has previously been shown that HIV infected individuals with
      pneumonitis have identifiable abnormalities in alveolar macrophages obtained by
      bronchoalveolar lavage (BAL). In particular, alterations in the expression of
      alveolar macrophage surface antigens associated with macrophage function have
      been reported. To determine whether these changes reflect HIV infection or the
      respiratory episode itself, a population of HIV infected patients with no
      respiratory disease was studied. METHODS: Twenty two HIV antibody positive
      individuals with a peripheral blood CD4 count of > 400/microliters and 10 healthy
      volunteer controls underwent bronchoscopy and BAL. Cytospin preparations from the
      recovered cells were stained using immunoperoxidase and double immunofluorescence
      techniques with monoclonal antibodies RFD1, RFD7, EBM11/CD68 (mature
      macrophages), UCHM1/CD14 (monocyte marker), and HLA-DR (RFDR1). Differential cell
      counts were also performed. RESULTS: There was an increase in overall alveolar
      macrophage HLA-DR expression in the HIV population. This was not reflected in a
      change in the percentage of cells staining CD14 (monocytes) or CD68 (mature
      macrophages) positive. The relative proportions of cells staining RFD1 + RFD7-
      (inducer cells), RFD1 - RFD7+ (effector cells), and RFD1 + RFD7+ (suppressive
      cells) were unchanged between HIV and control groups. CONCLUSIONS: In a
      population of HIV infected individuals with normal CD4 counts and no respiratory
      disease there was an increase in overall alveolar macrophage HLA-DR expression
      which occurred independently of any alteration in the relative proportions of
      alveolar macrophage subpopulations.

PMID- 7570416
TI  - Combined pulmonary and thoracic wall resection for stage III lung cancer.
AB  - BACKGROUND: Carcinoma of the lung with thoracic wall involvement constitutes
      stage III disease. The management of patients with this condition is complicated.
      However, improvement in perioperative care coupled with advances in surgical
      technique have enabled a more aggressive approach to the problem to be adopted.
      METHODS: A retrospective review was carried out of 58 patients (40 men) of mean
      age 63 years who underwent thoracotomy for lung cancer with chest wall invasion
      between 1980 and 1993. RESULTS: Chest wall resection was performed in 55 patients
      (94.8%); in three patients the discovery of N2 disease at operation precluded
      resection. The TNM status was T3N0M0 in 38 patients, T3N1M0 in 13, and T3N2M0 in
      seven. Squamous cell carcinoma was the commonest cell type (26 patients).
      Reconstruction of the chest wall was performed in 29 patients (Marlex mesh in
      six, Marlex-methacrylate in 22, myocutaneous flap in one patient). The morbidity
      and mortality were 22.4% and 3.4% respectively. Follow up was complete in 51
      patients. Nineteen (37.2%) survived > or = 5 years. The absolute five year
      survival for N0 and N1 disease was 44.7% and 38.4%, respectively. No patients
      with N2 disease survived five years. CONCLUSIONS: In patients with carcinoma of
      the lung and chest wall invasion, combined pulmonary and thoracic wall resection
      offers the prospect of cure with minimal morbidity and mortality. The prognosis
      of patients with coexistent N2 disease remains poor.

PMID- 7570418
TI  - Phrenic neuropathy in chronic renal failure.
AB  - BACKGROUND: Peripheral neuropathy and alterations in diaphragmatic muscle
      function are frequently caused by uraemia. Phrenic nerve function in patients
      with end stage renal failure, however, has not been examined to date. METHODS: An
      electrophysiological study of the phrenic nerve was performed to determine its
      possible involvement in 32 nondiabetic patients with end stage renal disease
      undergoing chronic haemodialysis. RESULTS: Seventeen patients had
      electrophysiological signs of peripheral neuropathy in at least one of the
      investigated nerves and 14 of the 17 showed pathological phrenic nerve latencies.
      Delayed phrenic nerve latencies correlated clearly with pathological peroneal
      nerve conduction velocities. CONCLUSIONS: Phrenic neuropathy is a frequent
      complication of uraemia.

PMID- 7570417
TI  - Effects of topical budesonide on epithelial restitution in vivo in guinea pig
      trachea.
AB  - BACKGROUND: Continuous epithelial shedding and restitution processes may
      characterise the airways in diseases such as asthma. Epithelial restitution
      involves several humoral and cellular mechanisms that may potentially be affected
      by inhaled anti-asthma drugs. The present study examines the effect of a topical
      steroid on epithelial restitution in vivo in the guinea pig. METHODS: The airway
      epithelium was mechanically removed from well defined areas of guinea pig trachea
      without surgery and without damage to the basement membrane or bleeding. An anti
      inflammatory dose of budesonide (1 mg) was administered repeatedly to the
      tracheal surface by local superfusion 24 hours before, at (0 hours), and 24 hours
      after the denudation. Migration of epithelial cells, formation of a plasma
      exudation-derived gel, and appearance of luminal leucocytes were recorded by
      scanning electron microscopy. Cell proliferation was visualised by
      bromodeoxyuridine immunohistochemistry and tissue neutrophils and eosinophils by
      enzyme histochemistry. RESULTS: Immediately after creation of the denuded zone
      ciliated and secretory cells on its border dedifferentiated, flattened out, and
      migrated speedily (mean (SE) 2.3 (0.3) micron/min) over the basement membrane.
      After 48 hours the entire denuded zone (800 microns wide) was covered by a
      tightly sealed epithelium; at this time increased proliferation was observed in
      new and old epithelium and subepithelial cells. Budesonide had no detectable
      effect on epithelial dedifferentiation, migration, sealing, or proliferation.
      Immediately after denudation and continuously during the migration phase plasma
      was extravasated creating a fibrinous gel rich in leucocytes, particularly
      neutrophils, over the denuded area. Budesonide had no effect on either the gel or
      the leucocyte density. CONCLUSIONS: These observations suggest that topical
      glucocorticoids may not interfere with a fast and efficient restitution of the
      epithelium in the airways.

PMID- 7570421
TI  - Three cases of pulmonary aspergilloma in adult patients with cystic fibrosis.
AB  - Pulmonary aspergillomas usually occur when Aspergillus fungi colonise lung tissue
      previously damaged by disease. Pulmonary aspergillomas in three adult patients
      with cystic fibrosis are reported--an association not previously described. At
      the time of diagnosis all three patients had previous long term colonisation with
      Aspergillus fumigatus and severe advanced destructive lung disease with lung
      function less than 25% of the predicted normal values. It is likely that, with
      increasing survival in cystic fibrosis, more adult patients will develop
      aspergillomas during the protracted phase of end stage lung disease that
      characterises the terminal years of this condition.

PMID- 7570419
TI  - Different perceptions of disease severity and self care between patients with
      cystic fibrosis, their close companions, and physician.
AB  - BACKGROUND: An investigation was carried out to determine whether patients with
      cystic fibrosis, their close companions, and physician perceived the severity of
      the disease and the level of patient self care similarly. METHODS: Sixty adults
      with cystic fibrosis (16-44 years), their close companion, and physician
      independently completed scales measuring their perceptions of disease severity
      and patient self care on three occasions over a two year period. Percentage
      predicted forced expiratory volume in one second (FEV1) and forced vital capacity
      (FVC), Shwachman score, and weight for height were recorded following each
      assessment. RESULTS: Patients and close companions considered the disease to be
      less severe than their physician. Fifty patients (83%) rated their health as
      "above/well above average", and 49 (82%) close companions rated the patient's
      health in the same way, but only 21 (35%) patients were considered by their
      physician to have mild disease. Differences also emerged in the estimation of
      patient self care; 48 close companions (80%) rated patients as "very good" or
      "excellent" in their self care, compared with 26 (44%) of the patients
      themselves. Only nine patients (15%) were considered to achieve this level of
      self care by their physician. Over the two year period the physician's ratings of
      severity increased in accordance with the decline in lung function. Patients'
      perceptions remained unchanged. CONCLUSIONS: From the physician's view-point,
      patients and close companions underestimate the severity of cystic fibrosis and
      overestimate patient self care. Patients' perceptions remain constant over time
      even when their health is clinically deteriorating.

PMID- 7570420
TI  - Sleep-related breathing disorder.2. Pathophysiology of obstructive sleep apnoea.

PMID- 7570422
TI  - Pseudomembranous necrotising bronchial aspergillosis complicating chronic airways
      limitation.
AB  - Pseudomembranous necrotising bronchial aspergillosis is a variety of invasive
      aspergillosis found in immunosuppressed patients. A case is presented of a 66
      year old woman whose only underlying disease was chronic airways limitation. The
      pathological findings and clinical implications are discussed.

PMID- 7570423
TI  - Treatment of pulmonary aspergilloma in cystic fibrosis by percutaneous
      instillation of amphotericin B via indwelling catheter.
AB  - Pulmonary aspergilloma is a rare complication of cystic fibrosis and is a
      contraindication to transplantation. The elimination of an aspergilloma in a 24
      year old patient with cystic fibrosis by percutaneous instillation of
      amphotericin B is described, enabling her to be accepted on a lung
      transplantation programme.

PMID- 7570424
TI  - Colonisation with Aspergillus of an intralobar pulmonary sequestration.
AB  - Pulmonary sequestration is a term used to describe an area of embryonic lung
      tissue supplied by an anomalous systemic artery. Two forms are recognised
      extralobar and intralobar-with different clinical presentations. A patient is
      reported with intralobar pulmonary sequestration in the left lung and
      colonisation with Aspergillus which was successfully treated by lower lobectomy.

PMID- 7570425
TI  - Commentary: unusual manifestations of aspergillosis.

PMID- 7570426
TI  - Emergency treatment of asthma.

PMID- 7570427
TI  - Toxicity of isoniazid and rifampicin combination.

PMID- 7570428
TI  - HLA genetics and allergic disease.

PMID- 7570429
TI  - Polymorphonuclear leucocyte traffic in lung inflammation.

PMID- 7570430
TI  - Inhaled vasodilator therapy in acute lung injury: first, do NO harm?

PMID- 7570431
TI  - Long term benefits of rehabilitation at home on quality of life and exercise
      tolerance in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND--Pulmonary rehabilitation has been shown to have short term subjective
      and objective benefits for patients with chronic obstructive pulmonary disease
      (COPD). However, appropriately controlled studies have not previously been
      performed, nor have the benefits of different types of continuation programme for
      rehabilitation been investigated. Both these problems have been addressed in a
      single study of the long term effects of once monthly physiotherapy versus once
      weekly physiotherapy at home after a comprehensive home rehabilitation programme
      on quality of life and exercise tolerance in patients with COPD. METHODS--Thirty
      six patients with severe airways obstruction (mean SD) forced expiratory volume
      in one second (FEV1) 1.3(0.4) 1, FEV1/inspiratory vital capacity (IVC)
      37.2(7.9)%) were studied. Twenty three patients followed a rehabilitation
      programme at home for 18 months consisting of physiotherapy and supervision by a
      nurse and general practitioner. During the first three months all 23 patients
      visited the physiotherapist twice a week for a 0.5 hour session. Thereafter, 11
      patients (group A) received a session of physiotherapy once weekly while 12
      patients (group B) received a session of physiotherapy once a month. The control
      group C (13 patients) received no rehabilitation at all. Quality of life was
      assessed by the Chronic Respiratory Questionnaire, exercise tolerance by the six
      minute walking distance, and lung function by FEV1 and IVC. Outcome measures were
      assessed at baseline and at three, six, 12, and 18 months. RESULTS--Long term
      improvements in quality of life were found in patients in groups A and B, but not
      in those in group C compared with baseline, but these only reached significance
      in group B at all time points. Patients in group B had a higher quality of life
      than those in group C only at three and 12 months. There was a decrease in both
      six minute walking distance (at 12 and 18 months) and IVC (at three, 12, and 18
      months) in patients in group C compared with the baseline measurement. Between
      groups analysis showed no differences for six minute walking distance, FEV1, and
      IVC. CONCLUSIONS--This study is the first to show that rehabilitation at home for
      three months followed by once monthly physiotherapy sessions improves quality of
      life over 18 months. The change in quality of life was not associated with a
      change in exercise tolerance.

PMID- 7570432
TI  - Comparison of peak oxygen consumption during cycle and treadmill exercise in
      severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: In normal subjects treadmill exercise usually produces the greatest
      maximal oxygen consumption (VO2max). This may not be true for patients with
      severe chronic obstructive pulmonary disease (COPD) in whom bicycle exercise,
      which offers support for the shoulder girdle, may produce a higher oxygen
      consumption than treadmill exercise. The aim of this study was to determine which
      mode of exercise produced the greatest oxygen consumption in patients with severe
      COPD. METHODS: Eight patients with severe COPD (forced expiratory volume in one
      second (FEV1) more than three standardised residuals below predicted) exercised
      to a symptom limited maximum on a bicycle and on a treadmill on separate days.
      The workload on the bicycle wa increased by 10 watts each minute, and the
      treadmill gradient was increased by 2.5% alternate minutes whilst the speed
      remained constant. Measurements of oxygen consumption (VO2), ventilation (VE),
      heart rate, and oxygen saturation were made, and capillary blood gases were
      measured before and immediately after exercise. Lactate concentration was
      measured before and four minutes after exercise. RESULTS: There were no
      differences at peak exercise between the two forms of exercise for VO2 (median
      11.7 and 12.2 ml/min/kg for bicycle and treadmill, respectively), for VE (median
      26.6 and 25.0 l/min, respectively), and for heart rate (median 119 and 115
      beats/min, respectively). The median lactate levels after bicycle exercise were
      higher than those after the treadmill (2.42 v 0.94 mmol/l). CONCLUSIONS: Although
      only a small number of patients was studied and individual variability was large,
      there was no clear difference between the two forms of exercise. Regular bicycle
      exercise was unfamiliar to this group of patients and generated the greatest
      lactate response. The results do not support the hypothesis that bicycle exercise
      will produce a better performance in patients with severe COPD, but the two modes
      of exercise cannot be used interchangeably.

PMID- 7570433
TI  - Comparison of nebulised salbutamol and ipratropium bromide with salbutamol alone
      in the treatment of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Patients admitted with acute exacerbation of chronic obstructive
      pulmonary disease (COPD) are often prescribed ipratropium bromide in combination
      with a beta 2 agonist such as salbutamol. Studies have not shown any benefit in
      adding ipratropium bromide to salbutamol in acute exacerbations of COPD, but
      these studies have only assessed patients for 60-90 minutes and short term
      studies may not predict long term clinical response. Combination therapy with the
      two drugs was compared with salbutamol alone in the treatment of acute
      exacerbations of COPD during a hospital admission. METHODS: Seventy patients
      admitted to hospital with an acute exacerbation of COPD were randomly allocated
      to receive either nebulised salbutamol 5 mg and ipratropium bromide 500
      micrograms, or nebulised salbutamol 5 mg alone (all four times a day) on
      admission. All other treatment was prescribed at the discretion of the attending
      physician. Length of stay in hospital and spirometric values on days 1, 3, 7, 14,
      and discharge were assessed. Patients completed a subjective symptom score each
      day. RESULTS: There was no difference between the two groups in the mean (SD)
      length of stay (salbutamol 10.5 (4.7) days, salbutamol + ipratropium bromide 11.8
      (4.4) days; 95% CI -1.02 to 3.62). There was no difference in spirometric values
      on days 1, 3, 7, 14, or discharge between the two groups. The subjective
      improvement was similar with both treatments. CONCLUSIONS: The routine addition
      of nebulised ipratropium bromide to salbutamol appears to be of no benefit in the
      treatment of acute exacerbations of COPD.

PMID- 7570435
TI  - Differences in aerodynamic particle size distributions of innovator and generic
      beclomethasone dipropionate aerosols used with and without a large volume spacer.
AB  - BACKGROUND: The equivalence of generic beclomethasone dipropionate (BDP)
      formulations with their innovator counterpart must be demonstrated if generic
      formulations are to be used. This study has examined the aerodynamic particle
      size distributions of both innovator and generic formulations of BDP and the
      effect of a large volume spacer (Volumatic) on these distributions. METHODS:
      Aerosol clouds of three formulations of BDP delivering 250 micrograms per metered
      dose were characterised using a high precision multistage liquid impinger, and
      the amount of drug in different particle size bands was determined by
      spectrophotometric assay. RESULTS: The mean (SD) respirable fractions of
      Becloforte, Beclazone, and Filair without the spacer (n = 10) were 24.1 (2.1)%,
      23.1 (2.7)%, and 23.0 (2.1)% respectively; however, the ratio of deposition on
      stage 4 of the impinger to that on stage 3 was lower for Beclazone and for Filair
      than for Becloforte, implying a smaller proportion of fine particles for the
      generic products. When the three products delivered via the Volumatic spacer
      device were compared, the respirable fraction for Becloforte (n = 10) was 25.0
      (4.0)%, but those of Beclazone (n = 10) and Filair (n = 11) were 16.0 (1.9)% and
      14.6 (3.4)%. Repeat testing (n = 5) at a later date showed higher mean respirable
      fractions for all three products, but a trend towards the highest respirable
      fraction for Becloforte, and the same rank order for the other two products.
      CONCLUSIONS: These in vitro findings suggest that the particle size distributions
      of the two generic formulations of BDP are not equivalent to that of the
      innovator product. Some differences in particle size distributions might not have
      been detected by a twin impinger. Clinical testing would be required to assess
      the therapeutic equivalence of innovator and generic corticosteroid products used
      with or without spacer devices.

PMID- 7570434
TI  - Hormonal, renal, and autonomic nerve factors involved in the excretion of sodium
      and water during dynamic salt and water loading in hypoxaemic chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease
      (COPD) develop sodium and water retention and a subclinical autonomic neuropathy.
      The possibility that these might be associated has been investigated. METHODS:
      The ability of 24 patients with COPD to excrete a 6 ml/kg 2.7% intravenous saline
      or 15 ml/kg oral water load was studied and changes in plasma electrolyte levels,
      osmolality, plasma aldosterone and vasopressin levels, urinary volume and sodium
      content, glomerular filtration rate, renal blood flow, and cardiovascular
      autonomic nerve function were measured. Patients were divided into groups of
      eight: those in group A (controls) had mild COPD with a Pa02 of > 9 kPa and no
      oedema, patients in group B were more hypoxaemic but had never been oedematous,
      whilst those in group C were hypoxaemic and mildly oedematous at the time of the
      study. RESULTS: Patients in groups B and C excreted less sodium and water during
      saline loading and a lesser proportion of the water load. Patients in group C had
      a reduction in renal blood flow and glomerular filtration rate and all had a
      subclinical autonomic neuropathy, which was also found in three patients in group
      B. Their plasma aldosterone level was raised but did suppress appropriately on
      saline loading. Vasopressin levels were abnormally raised for the osmolality in
      patients in group C and in those with autonomic dysfunction throughout the water
      load and at 240 minutes after the salt load. Sodium and urine excretion was
      highly correlated with autonomic dysfunction, aldosterone levels at time zero,
      and renal blood flow. The 11 patients with autonomic dysfunction were more likely
      to be oedematous, more hypoxaemic, excreted much less urine and sodium, had lower
      glomerular filtration rate and renal blood flow, and higher aldosterone and
      vasopressin levels than the remaining patients. CONCLUSIONS: In patients with
      COPD the inability to excrete sodium and water is multifactorial. This is the
      first study to show that autonomic dysfunction is at least associated and might
      play an important part in the impaired sodium and water homeostasis seen in
      patients with severe COPD.

PMID- 7570436
TI  - Peak flow based asthma self-management: a randomised controlled study in general
      practice. British Thoracic Society Research Committee.
AB  - BACKGROUND: Peak flow based asthma self-management plans have been strongly
      advocated in consensus statements, but convincing evidence for the effectiveness
      of this approach has been largely lacking. METHODS: A randomised controlled trial
      was conducted in 25 general practices comparing an asthma self-management
      programme based on home peak flow monitoring and surgery review by a general
      practitioner or practice nurse with a programme of planned visits for surgery
      review only over a six month period. RESULTS: Seventy two subjects (33 in the
      self-management group and 39 in the planned visit group) completed the study
      protocol, but diary card data for at least three months were available on a total
      of 84 (39 in the self-management group and 45 in the planned visit group).
      Teaching self-management took longer than the planned visit review. In the self
      management group home peak flow monitoring was felt to be useful by doctors and
      patients in 28 (85%) and 27 (82%) cases, respectively. There were no between
      group differences during the study period in terms of lung function, symptoms,
      quality of life, and prescribing costs. Only within the self-management group
      were improvements noted in disturbance of daily activities and quality of life.
      Possible explanations for these negative results include small numbers of
      subjects, the mild nature of their asthma, and inappropriate self-management
      strategies for such patients. CONCLUSIONS: Rigid adherence to long term daily
      peak flow measurement in the management of mild asthma in general practice does
      not appear to produce large changes in outcomes. Self-management and the use of
      prescribed peak flow meters need to be tailored to individual circumstances.

PMID- 7570437
TI  - Gamma/delta T lymphocytes in the blood of patients with sarcoidosis.
AB  - BACKGROUND: Gamma/delta T lymphocytes are thought to have a role in granulomatous
      immune responses at peripheral sites of antigen contact such as the gut, skin and
      lung. The aim of this study was to determine if gamma/delta T lymphocytes are
      increased in the peripheral blood of patients with active sarcoidosis. METHODS:
      Peripheral blood from 21 untreated patients with a new presentation of
      sarcoidosis (12M, 9F), 20 normal volunteers (12M, 8F), and 12 patients with
      cavitary pulmonary tuberculosis were subjected to Ficoll Hypaque separation and
      flow cytometry analysis using monoclonal antibodies to CD3, 4, 8, 25, HLA-DR and
      gamma/delta T cell receptor. RESULTS: All patients with sarcoidosis had
      compatible chest radiographs and all were Mantoux negative in spite of previous
      BCG vaccination. In all but one patient histological examination showed non
      caseating granuloma. There was no difference in the mean percentage or absolute
      numbers of gamma/delta positive peripheral blood lymphocytes between the three
      populations. Thirteen patients with sarcoidosis had an absolute lymphopenia and
      the mean percentage of CD3 positive peripheral blood lymphocytes in the group
      with sarcoidosis was lower than the other two groups. The percentage of CD25 and
      HLA-DR positive cells was higher in the group with sarcoidosis, supporting the
      fact that these patients had active disease. CONCLUSION: Gamma/delta T
      lymphocytes are not increased in the peripheral blood of patients with
      sarcoidosis and are unlikely to have a role in the pathogenesis of this disease.

PMID- 7570438
TI  - Follow up of an immunocompromised contact group of a case of open pulmonary
      tuberculosis on a renal unit.
AB  - BACKGROUND: The organisation, management, outcome and cost of follow up of a
      large group of mainly immunocompromised patients and healthcare workers who were
      exposed to a staff member of a London renal unit with smear positive pulmonary
      tuberculosis are described. METHODS: Following British Thoracic Society (BTS)
      guidelines, 576 close contacts were identified and divided into three groups: (1)
      303 renal patients including 61 with renal transplants; (2) 90 surgical patients;
      and (3) 183 staff members. Screened contacts were interviewed, completed a
      symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux
      test if appropriate with referral to a chest physician if required. RESULTS:
      Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first
      screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one
      transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal
      patients had died before screening and 11 deaths occurred after first interview.
      One case of tuberculosis epidemiologically related to the index case was
      diagnosed on clinical criteria. A review of the case records and/or death
      certificates and entries on to tuberculosis registers indicated no further cases.
      The cost of the investigation was estimated to be approximately franc25 000, or
      franc44 per contact screened, with staff costs comprising 79% of the total.
      CONCLUSIONS: Undiagnosed tuberculosis in healthcare workers working with
      immunosuppressed patients can lead to large and expensive follow up studies. The
      applicability of the 1990 and 1994 BTS guidelines to the investigation of
      tuberculosis in an immunocompromised nosocomial group, and the role of the
      infection control doctor and the consultant in Communicable Disease Control in
      overlapping nosocomial and community incidents, are discussed.

PMID- 7570439
TI  - Relation of bronchoalveolar lavage T lymphocyte subpopulations to rate of
      regression of active pulmonary tuberculosis.
AB  - BACKGROUND: Effective host defence against mycobacterial infection chiefly
      depends on the interactions between macrophages and T lymphocytes. This study
      investigated the relation of cellular components and their activity of cells
      obtained by bronchoalveolar lavage (BAL) from the lower respiratory tract to
      disease regression in patients with active pulmonary tuberculosis without HIV
      infection. METHODS: Clinical indices including age, sex, the presence of
      diabetes, fever, the presence of resistant strains of mycobacteria, the bacterial
      load in sputum, and disease extent on chest radiography at presentation were
      assessed before commencing four-drug antituberculous therapy. Twenty two patients
      with active pulmonary tuberculosis were divided into rapid, intermediate, and
      slow regression groups. Subpopulations of alveolar macrophages separated using
      discontinuous Percoll density gradient centrifugation and T lymphocytes (with
      CD3, CD4, CD8, and CD25 monoclonal antibodies) were quantified. RESULTS: There
      were no differences among rapid, intermediate, and slow regression groups in
      terms of age, sex, the presence of diabetes, the presence of resistant strains of
      mycobacteria, or the bacterial load in sputum. No differences were found between
      the groups in terms of subpopulations of alveolar macrophages or numbers of CD3
      and CD4 lymphocytes. By contrast, an increase in CD8 cells was shown in the slow
      regression group compared with the rapid and intermediate regression groups. CD25
      cell numbers were increased in the rapid regression group compared with the slow
      regression group. The CD4/CD8 ratio was decreased in the slow regression group
      compared with the rapid and intermediate regression groups and the relation
      between the proportion of CD25 cells and the CD4/CD8 ratio in BAL fluid was
      significant. CONCLUSIONS: A decreased CD4/CD8 ratio with an increase in CD8 cells
      in the alveolar spaces was associated with slow disease regression in patients
      with active pulmonary tuberculosis without HIV infection, suggesting that the
      balance of T lymphocyte subsets may play a central part in the modulation of host
      defence against mycobacterial infection.

PMID- 7570441
TI  - DNA concentration and length in sputum of patients with cystic fibrosis during
      inhalation with recombinant human DNase.
AB  - BACKGROUND: The clinical benefit of the administration of aerosolised recombinant
      human DNase (rhDNase) on pulmonary function in patients with cystic fibrosis has
      already been demonstrated but the biochemical action of rhDNase on DNA in
      bronchial secretions in vivo has not yet been investigated. METHODS: Sputum was
      collected from 135 patients with cystic fibrosis before and during treatment with
      aerosolised rhDNase and examined to ascertain DNA concentration and length by
      colorimetric assay and densitometry of gel separated DNA. RESULTS: Treatment with
      rhDNase reduced the concentration and the size of extracellular DNA in the
      sputum. The median interquartile range of DNA length decreased from 0.5-2.6 kbp
      before treatment to 0.3-1.0 kbp during treatment. CONCLUSIONS: rhDNase was
      delivered to the secretions and was enzymatically active in vivo.

PMID- 7570440
TI  - Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle
      responses in vitro.
AB  - BACKGROUND: Sodium metabisulphite (MBS) is known to induce bronchoconstriction in
      asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on
      neurally mediated contraction in vitro have been examined. METHODS: Tracheal and
      bronchial airway segments were placed in oxygenated buffer solution and
      electrical field stimulation was performed in the presence of indomethacin (10(
      5) M) and propranolol (10(-6) M) for the measurement of isometric tension.
      Atropine (10(-6) M) was added to bronchial tissues. RESULTS: Concentrations of
      MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and
      did not alter either tracheal smooth muscle contraction induced by electrical
      field stimulation at all frequencies or acetylcholine-induced tracheal smooth
      muscle contraction. There was a similar response in the absence of epithelium,
      except for potentiation of the response induced by electrical field stimulation
      at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M)
      augmented neurally-mediated non-adrenergic non-cholinergic contractile responses
      in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had
      no effect on the contractile response induced by substance P, but at higher
      concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of
      responses induced by either electrical field stimulation or exogenously applied
      acetylcholine or substance P. CONCLUSIONS: MBS had no direct contractile
      responses but enhanced bronchoconstriction induced by activation of non
      cholinergic neural pathways in the bronchus, probably through increased release
      of neuropeptides. At high concentrations MBS inhibited contractile responses
      initiated by receptor or neural stimulation.

PMID- 7570442
TI  - Sleep-related breathing disorder . 3. How to reach a diagnosis in patients who
      may have the sleep apnoea/hypopnoea syndrome.

PMID- 7570443
TI  - Malignant mesothelioma: new insights into tumour biology and immunology as a
      basis for new treatment approaches.

PMID- 7570445
TI  - Comparison of the single breath with the intrabreath method for the measurement
      of the carbon monoxide transfer factor in subjects with and without airways
      obstruction.
AB  - BACKGROUND: Measurement of the carbon monoxide transfer factor (TLCO) has
      traditionally been performed using the single breath method but recently the
      intrabreath method has been developed. The aim of this study was to compare the
      two methods in the clinical evaluation of patients with obstructive and non
      obstructive pulmonary disorders. METHODS: Measurements of TLCO with the
      intrabreath method were carried out on a study sample composed of 50 patients
      with non-obstructive disorders and 50 with airways obstruction (FEV1/FVC < 70%)
      either before or after a single breath measurement of the TLCO had been
      performed. The method involves the continuous analysis of a single slow expirate
      using a computerised rapid multigas infrared analyser. TLCO, alveolar volume
      (VA), TLCO/VA, and inspired vital capacity (IVC) values were obtained for both
      groups by both methods. RESULTS: When measured with the intrabreath method the
      group with airways obstruction showed lower TLCO and TLCO/VA values than the non
      obstructive group. VA was higher in both patient groups when measured with the
      intrabreath technique. The same test also showed higher TLCO values with the
      intrabreath method in the group with non-obstructive disorders and lower TLCO/VA
      values with the intrabreath method in those with airways obstruction. The
      corresponding parameters obtained by the two methods correlated closely, with no
      correlation between the magnitude of the differences with the magnitude of the
      readings. An index of gas mixing indicated a better distribution of the inspired
      air for the intrabreath method than for the single breath method. The VA values
      obtained with the intrabreath method showed a closer agreement to the actual
      total lung capacities measured by body plethysmography. CONCLUSION: The
      intrabreath method of determining TLCO is comparable to the traditional single
      breath method. Measurement of alveolar volume by the intrabreath method
      approximates more closely to total lung capacity, even in subjects with airways
      obstruction.

PMID- 7570447
TI  - Primary amyloidosis presenting as an isolated mediastinal mass: diagnosis by fine
      needle biopsy.
AB  - Intrathoracic amyloidosis affecting the lungs or mediastinum is rare, and
      mediastinal lymphadenopathy in the absence of pulmonary involvement is even more
      rare. The case history is presented of a previously healthy man who developed
      nodular mediastinal amyloidosis without pulmonary involvement. Diagnosis was made
      by percutaneous fine needle biopsy.

PMID- 7570446
TI  - Herpetic bronchitis with a broncho-oesophageal fistula.
AB  - Tracheobronchitis and oesophagitis due to herpes simplex virus (HSV) are rare.
      Tracheo-oesophageal fistula due to HSV oesophagitis has been described in the
      immunocompromised host. A case is reported of a broncho-oesophageal fistula which
      developed secondary to herpetic bronchitis in an apparently immunocompetent
      patient.

PMID- 7570448
TI  - Adult congenital lobar emphysema in pregnancy.
AB  - A young woman presented with left sided chest pain. Chest radiography revealed a
      hyperexpanded left upper lobe and the rare diagnosis of congenital lobar
      emphysema was made. She was then found to be pregnant. Thoracotomy and left upper
      lobectomy were performed during the pregnancy without adverse effects to the
      mother or fetus. The implications of pregnancy on the surgical management of this
      rare condition are discussed.

PMID- 7570450
TI  - Parathyroid cyst of the thymus.
AB  - A case is described of primary hyperparathyroidism in a patient with both a
      parathyroid cyst within the thymus gland and a concomitant parathyroid adenoma.
      The parathyroid adenoma contained microcystic areas of degeneration, and it is
      thought that the parathyroid cyst reflected degenerative change in a pre-existing
      adenoma. Parathyroid cyst should be considered in the differential diagnosis of
      cystic lesions within the thymus. Fine needle aspiration and parathyroid hormone
      assay on cyst fluid may provide a preoperative diagnosis.

PMID- 7570444
TI  - Airway smooth muscle relaxation.

PMID- 7570453
TI  - Vegetarian diet and tuberculosis in immigrant Asians.

PMID- 7570452
TI  - Vegetarian diet and tuberculosis in immigrant Asians.

PMID- 7570451
TI  - Pleural mesothelioma with non-Hodgkin's lymphoma.

PMID- 7570454
TI  - Control and prevention of tuberculosis in the UK.

PMID- 7570455
TI  - Air pollution and COPD.

PMID- 7570449
TI  - Massive haemoptysis complicating prosthetic patch pulmonary embolism after atrial
      septal defect repair.
AB  - A case is presented of a 43 year old woman with massive haemotypsis secondary to
      non-thrombotic pulmonary embolism complicating atrial septal defect repair with a
      prosthetic patch. Non-thrombotic embolus must be considered in the differential
      diagnosis of massive haemoptysis.

PMID- 7570456
TI  - Dietary fish oil and airways obstruction.

PMID- 7570458
TI  - Perception, personality, and respiratory control in life-threatening asthma.

PMID- 7570459
TI  - Smoking cessation: time for action.

PMID- 7570457
TI  - Relationship of acute obstructive airway change to chronic (fixed) obstruction.

PMID- 7570460
TI  - Neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer.

PMID- 7570461
TI  - Stenting of superior vena caval obstruction.

PMID- 7570463
TI  - Chlamydia pneumoniae: defining the clinical spectrum of infection requires
      precise laboratory diagnosis.

PMID- 7570462
TI  - Escalating threat from tuberculosis: the third epidemic.

PMID- 7570464
TI  - Mechanisms of the adult respiratory distress syndrome: selectins.

PMID- 7570465
TI  - Asthma and the beta agonist debate.

PMID- 7570468
TI  - 1st Congress of the European Association for Clinical Pharmacology and
      Therapeutics, Paris, France, 27-30 September 1995, and Synthelabo Symposium Alpha
      1-blockers in BPH Uroselectivity and Quality of Life. Abstracts.

PMID- 7570469
TI  - [Diseases of the poor. Anniversary of the WHO tropical disease research project].

PMID- 7570470
TI  - [Give a lift to psychiatry!].

PMID- 7570466
TI  - Oxidants/antioxidants in idiopathic pulmonary fibrosis.

PMID- 7570467
TI  - Bronchiolitis obliterans with organising pneumonia: outcome.

PMID- 7570471
TI  - [Edema and pain in the leg--how to benefit from magnetic tomography?].

PMID- 7570472
TI  - [Magnetic tomography in the examination of edema and pain in the leg].
AB  - Magnetic resonance imaging (MRI) was used to investigate 38 patients suffering
      from leg oedema or pain of various etiology. Spin echo series with 10 mm
      transverse slices of both legs were obtained. Soft tissue changes were visualized
      best by T2-weighted sequences. Characteristic changes could be observed by MR
      images of patients with closed compartment syndrome (n = 2), chronic lymph oedema
      (n = 10) and post-reconstructive leg oedema following vascular surgery (n = 14).
      MRI can also show typical soft tissue changes in patients with deep vein
      thrombosis (n = 5) or post-thrombotic syndrome (n = 3). For most of these
      conditions, the diagnosis can usually be established using simpler methods.
      However, MRI is an excellent supplementary method for showing soft tissue
      changes, and is a promising way of investigating conditions that may give rise to
      leg oedema and pain.

PMID- 7570473
TI  - [Prognostic value of neuroendocrine activation after acute myocardial
      infarction].
AB  - Complex neurohumoral activation is associated with acute myocardial infarction.
      Either as a cause of adverse events or as a marker of haemodynamic status,
      augmented neurohumoral activation is associated with decreased short- and long
      term survival. Although the predictive value of neurohumoral assessment is
      generally reduced after adjustment for demographic, clinical and haemodynamic
      variables in multivariate models, recent data suggest that determination of
      circulating neurohormone concentrations may provide significant, independent
      prognostic information in cases of acute myocardial infarction. The clinical
      usefulness of neurohumoral determination as a risk stratification tool and as a
      method of identifying patients who might benefit from therapeutic intervention
      remains to be established.

PMID- 7570474
TI  - [Meningitis after myelography].
AB  - Lumbar myelography is still frequently used in cases of suspected lumbar
      radiculopathy. Since 1984, iohexol has been the contrast medium of choice in
      myelography, and so far only a few cases of chemical meningitis have been
      reported. Bacterial meningitis cannot be distinguished from chemical meningitis
      on the basis of clinical findings. A cerebrospinal fluid Gram stain and culture
      are the only truly reliable tests in deciding the etiology of the meningitis. We
      describe two patients who developed meningitis following myelography with
      iohexol. In one of the patients, the cerebrospinal fluid culture was positive
      with subsequent identification of Flavobacterium meningosepticum, a species not
      previously reported as an infectious agent in meningitis after myelography.

PMID- 7570477
TI  - [Diagnostic evaluation of suspected reactive arthritis].
AB  - On the basis of an epidemiological study on recently onset, possible reactive
      arthritides in Oslo we propose a programme for diagnostic evaluation. Disease
      symptoms and signs provided little help for an ethiological diagnosis. Therefore
      a variety of diagnostic tests and examinations are recommended in order to obtain
      a correct diagnosis; such as clinical examination, chemical and serological blood
      tests, bacteriological examinations from throat, of stools and of specimens from
      urethra-cervix, examination of synovial fluid and synovial tissue and X-ray
      examination of affected joints, sacroiliacal joints and lungs. About one third of
      the recently onset arthritides in the Oslo study were diagnosed as reactive
      arthritis, one third as possible reactive arthritis and another third as
      inflammatory arthritides.

PMID- 7570475
TI  - [Fluorosis. Experiences based on two cases].
AB  - Since 1961 sodium fluoride has been an alternative in the treatment of
      osteoporosis, although there is still some difference of opinion between
      endocrinologists regarding the effect on pain and occurrence of fracture of the
      vertebral column. Two cases are reported, both treated for postmenopausal
      osteoporosis with calcium, vitamin D and sodium fluoride for longer periods over
      many years, and with good effect on pain and tendency to lumbar vertebral body
      fracture. In both patients the diagnosis of skeletal fluorosis was delayed for
      several years, mainly because information about this treatment never reached the
      radiologist. When the diagnosis was eventually established after the radiologist
      himself had made inquiries to the referring physician, the patients had in the
      meanwhile undergone several unnecessary supplementary examinations because of
      suspected cancer metastasis.

PMID- 7570476
TI  - [Exposure to anesthetic gases].
AB  - In recent years there has been a growing awareness of possible hazards caused by
      anaesthetic gases in operating theatres. Our study monitored ambient nitrous
      oxide (N2O) levels in the operating theatres and recovery rooms at the University
      Hospital in Tromso. The results show that exposure to waste anaesthetic gases
      occurs because of leaks in the anaesthetic equipment. The three major sources of
      leaks are masks, high pressure fittings and exhalation valves. Prevention of
      leakage from equipment is very important, and a leakage testing programme should
      be an essential part of the daily control strategy. Good working practices and
      tracheal intubation results in low exposure to nitrous oxide in the breathing
      zone of the anesthetic personnel. During mask anaesthesia we have observed
      nitrous oxide concentrations above 1500 ppm, owing to mask leakage. A closely
      fitting scavenging mask and good working practices lead to in lower nitrous oxide
      concentrations. Nitrous oxide exhalation from the patient in the recovery room is
      only a minor problem.

PMID- 7570478
TI  - [Repetition and private exams--the road to medical studies. Extent, financing and
      social consequences of collecting of grades for medical studies in Norway].
AB  - This article is based on a survey of Norwegian freshmen medical students in
      autumn 1993. Norwegian medical students are selected mainly by grades from the
      upper secondary school, and the purpose of this study is to shed light on the
      extent of repetition of exams among the entrants, emphasizing differences by
      gender and social background. A wide range of activities are associated with
      improvement of grades, including a high rate of attendance at private school.
      Most students are recruited from the upper social strata, and children of
      physicians are remarkably overrepresented. The unintended consequences of the
      selection mechanisms are discussed.

PMID- 7570479
TI  - [Resistance development of major pathogenic bacteria].
AB  - In recent years the emergence of strains of drug-resistant bacteria has become a
      major health problem in many parts of the world. This has made it vitally
      necessary both to develop new antibacterial drugs and establish effective
      strategies to combat invading bacteria. In Norway, drug-resistant bacteria are a
      minor problem as yet, but the situation could change quite quickly if the
      necessary precautions are not taken. These include not prescribing antibacterial
      drugs too freely, and thoroughly surveying the extent of drug-resistance in an
      attempt to confine and prevent infection with resistant bacteria.

PMID- 7570480
TI  - [Is there a connection between epilepsy and migraine?].
AB  - Sometimes it is difficult to distinguish between epilepsy and migraine on purely
      clinical basis. To illustrate some of these difficulties, the cases of three
      patients are described. The first patient had both epilepsy and migraine with
      aura, the second patient had paroxysmal headache as a part of an ictal, epileptic
      event, and the third patient presented a more complex clinical picture due to
      post traumatic encephalopathy. The paper deals with possible genetic, causal and
      EEG-related features which migraine and epilepsy have in common.

PMID- 7570482
TI  - [The Mayo Clinic--a medical Mekka in the Midwest].

PMID- 7570481
TI  - [Turnover of positions as the medically responsible physician in Norwegian
      municipalities 1988-91].
AB  - The aim of the study was to measure turnover in public health posts in Norwegian
      municipalities from 1 January 1988 to 31 December 1991. From various publications
      and a self-administered questionnaire mailed to the authorities in selected
      municipalities we identified 164 (37%) municipalities out of 445 with a change of
      doctor in the public health post. During the study period, about 200 different
      doctors had been employed in these 164 municipalities. Additionally, at least 200
      doctors had been engaged as public health officers on a short term basis. The
      findings indicate that counting announcements of vacant public health posts in
      the Journal of the Norwegian Medical Association is a reliable method for
      measuring turnover in such posts.

PMID- 7570483
TI  - [Schizophrenia--how much do we need for the cost of treatment and research?].

PMID- 7570484
TI  - [A national registry for cholecystectomy].

PMID- 7570487
TI  - [Rise and fall of primary care physicians with fixed salaries (1970-2000)].

PMID- 7570486
TI  - [Aortic dissection].

PMID- 7570488
TI  - [Alcohol--more than wine with meals].

PMID- 7570485
TI  - [Do Norwegian health services need Internet?].

PMID- 7570489
TI  - [Alcohol consumption among adolescents in 3 municipalities. A survey of local
      variations in alcohol consumption].
AB  - Drinking habits among 663 adolescents 14, 15, 17 and 18 years of age in three
      local communities were investigated by means of a questionnaire. Half had tasted
      alcohol already at the age of 14 years. The total amount consumed per person per
      year averaged 3.5 litres pure alcohol. Geographical variations in consumption
      were more than six-fold. At the age of 17 years, boys began to consume more than
      girls. In both sexes, home distilled spirits was the most common beverage
      obtained or provided illegally. The main reason for drinking alcohol seems to be
      to get drunk.

PMID- 7570490
TI  - [Development of drinking habit among adolescents. Factors connected with alcohol
      consumption].
AB  - Factors related to drinking habits among 663 adolescents 14, 15, 17 and 18 years
      old were investigated in three municipalities by means of a questionnaire. In a
      multiple regression analysis, variation in alcohol consumption was examined using
      several independent variables describing access to alcohol, behavioural factors,
      environmental influences, attitudes and demographic background. The most
      important factors predicting high alcohol consumption were early drinking debut,
      being away from home at night without the parents' knowledge, having friends who
      drink a lot and early high consumption of unhealthy foods such as soft drinks,
      peanuts and chips. All these factors were again related to upbringing and home
      environment.

PMID- 7570491
TI  - [Alcohol abusers after treatment at a clinic--a follow-up study].
AB  - Clients from Nord-Troondelag county that received residential treatment for
      alcohol problems were interviewed some two years after the index treatment.
      Treatment programmes were selected by the patients themselves from among those
      provided at one public and three private clinics, and the costs were covered
      partially or entirely borne by the municipality. It was possible to interview 80%
      (133/166) of those treated during the study period. The overall outcome was quite
      good, with 2/3 being abstinent and over 80% not having a current DSM-IIIR or S
      MAST defined alcohol problem at follow-up. Half (13/26) of those who had relapsed
      and were retreated were not drinking a year later. A survival analysis suggested
      that there were marked differences in relapse rates among those attending the
      different clinics. Small size, a warm, home-like atmosphere, and a clear
      presentation of the "Higher Power" concept were associated with the two clinics
      with fewer relapses, although the nature of the study does not allow inferences
      of causality. Other factors did not differentiate the more successful from the
      less successful clinics.

PMID- 7570492
TI  - [Aortic dissection. A 8-year material from health region 5].
AB  - At the University Clinic Tromso 27 and 16 patients with aortic dissection of
      Stanford type A and B have been admitted during the last eight years. The
      treatment strategy has been immediate surgery for type A and a conservative
      strategy consisting of blood pressure reduction and observation for type B. Nine
      (33%) of the patients with type A dissections were diagnosed either too late for
      surgery or at autopsy. Two were deemed too ill for operative treatment. One
      patient with a chronic type A dissection has been followed up without surgery.
      The remaining 15 were operated on. Four of these (26%) died within 30 days. Apart
      from a temporary hemiparesis, no sequelae related to the surgical treatment were
      observed in the remaining 11 patients. Six of the 16 patients with type B
      dissections were operated on because of organ ischemia or rupture/threatening
      rupture. Two died within 30 days. One patient had a prolonged postoperative
      course owing to multiple organ failure and muscle necrosis. Two of the ten
      patients with type B dissections who were followed up without surgery died during
      the observation period. These observations indicate a need for a more aggressive
      approach to the diagnosis and follow-up of aortic dissections.

PMID- 7570495
TI  - [Pseudomyxoma peritonei].
AB  - The article describes a case of pseudomyxoma peritonei. The disease is uncommon.
      The origin is usually a malignant process in the ovary or appendix. The disease
      spreads to the peritoneal surface, which becomes studded with mucinous bulks. The
      patient suffered from abdominal discomfort and distension. 80-85% of persons with
      this disease die within ten years. The disease must be treated with extensive
      surgery. The case demonstrates the effect of adjuvant chemotherapy. The treatment
      of pseudomyxoma peritonei must involve co-operation between surgery and oncology.

PMID- 7570494
TI  - [Erysipelothrix rhusiopathiae--a cause of erysipeloid and endocarditis].
AB  - Erysipelothrix rhusiopathiae is widespread among many species of animals
      including fish. Erysipeloid is the most common infection caused by this bacterium
      in man; systemic infection, with endocarditis, is rare. Most of the affected
      patients risk exposure to the organism at work. Two patients with E.
      rhusiopathiae infections are described; one with erysipeloid after slaughtering a
      deer, the other with fatal endocarditis after gutting an eel. Erysipeloid may be
      confused with "seal finger", but this disease probably has a different microbial
      etiology and requires different antibiotic treatment.

PMID- 7570493
TI  - [Hemifacial spasms. Causes, clinical findings and treatment].
AB  - Hemifacial spasm is a condition characterized by involuntary, episodic,
      synchronous contractions of muscles innervated by the facial nerve in one half of
      the face. The treatment can be medical or neurosurgical, but the most effective
      is injections of botulinum toxin. 13 patients who received this treatment for
      hemifacial spasm are described. The treatment of different forms of focal
      dystonias has been described before in this journal. The aetiology of hemifacial
      spasm is different from that of focal dystonia. It is probably due to compression
      of the facial nerve, causing ectopic generation of impulses. Treatment with
      botulinum toxin is shown to be effective also for this condition, but the dosage
      and the duration of effect differ from those reported for focal dystonias. This
      may be due to differences in the pathophysiological mechanisms of the two
      conditions.

PMID- 7570496
TI  - [Bladder rupture. Diagnosis, etiology and treatment].
AB  - The majority of bladder ruptures (80-90%) are caused by major blunt abdominal
      trauma. Penetrating injuries account for the rest. Bladder rupture is seen most
      often in patients with pelvic fracture. More seldom, the rupture can be caused by
      energetic blunt abdominal trauma. The rupture can either be intraperitoneal or
      extraperitoneal. The symptoms are macroscopic haematuria, suprapubic pain and, in
      some patients, an inability to avoid. Retrograde cystography is the diagnostic
      procedure of choice. An intravenous infusion pyelogram does not provide adequate
      examination of the bladder. The rupture is treated by operative closure and
      drainage by catheter. Extraperitoneal rupture may be treated with only catheter
      drainage and close clinical evaluation. We describe two patients with
      intraperitoneal bladder rupture after low energetic abdominal trauma.

PMID- 7570497
TI  - [Nucleotide excision repair in human cells. Biochemistry and implications in
      diseases].
AB  - It is of vital importance for all living systems to ensure proper functioning and
      propagation of their genetic information. A severe threat to the stability of DNA
      is posed by the ubiquitous occurrence of chemical and physical genotoxic agents
      that damage DNA, thus interfering with the processes of DNA metabolization and
      inducing mutations. This threat has necessitated the generation of an intricate
      network of DNA repair systems. Recently several laboratories have made great
      progress in the field of DNA repair, and have contributed to unravelling the
      molecular mechanism of the major process, the nucleotide excision repair pathway
      in mammals, and its biological impact and involvement in several human DNA repair
      disorders.

PMID- 7570498
TI  - ["Home monitoring" does not prevent crib death. Managing possibilities and
      results of new technology].
AB  - Each night, about 300 Norwegian infants are connected to monitors that register
      respiratory movement. Most of the infants are siblings to cot death victims. It
      has never been proven that these simple devices have saved lives in such cases.
      On the contrary it has happened that infants have succumbed to cot death while
      connected to such monitors. During the last ten years, 1,200 simple monitors for
      home use have been sold in Norway. In most cases these are owned by departments
      of pediatrics or by county centres for medical equipment, and are lent to
      families. The use of monitors varies considerably among the different counties.
      Thus in the county of Nordland 100 monitors are available, while Buskerud county
      has only two. Based on undocumented effect and great variation in availability,
      it seems appropriate to ask: what forces maintain home monitoring, and is it
      possible to discontinue this service? If no new and better technology is
      developed, it is necessary to consider the consequences of continuing to use
      ineffective devices. Conversely, it is also necessary to look at the consequences
      of discontinuing the service. Based on the present knowledge about risk factors,
      it would seem better to emphasize a dialogue between parents and doctor, rather
      than continue to use monitors.

PMID- 7570499
TI  - [Changing market for Oslo physicians. Justification for and consequences of
      changes in agreements].
AB  - During the 1970s the number of salaried general practitioners in Oslo rose to
      approximately half of all general practitioners in the city. However, during the
      last ten years, increasing differences in wages between general practitioners on
      salary and fee-for-service general practitioners has led to difficulties in
      recruiting doctors to salaried positions. As a result many doctors have
      negotiated new contracts with the sub-municipalities of Oslo, a typical
      arrangement being a combination of fee-for-service payment for work with patients
      and a fixed salary for one or two days per week for work in nursing homes and
      mother-and-child clinics. General practitioners in four sub-municipalities of
      Oslo reported better opportunities for recruiting staff, greater autonomy and
      higher income as the main driving forces behind the changes. The increase in
      income has indeed been formidable, approximately NOK 100,000-200,000 per year,
      depending on the specific contract. The number of consultations has increased
      substantially in centres where general practitioners have switched to fee-for
      service payment and waiting lists have been eliminated, partly as a consequence
      of higher turnover of consultations, and partly because of fewer vacant posts.
      The economic consequences to the municipalities are more uncertain, and the
      experiences of auxilliary staff in regard to the charges that have occurred are
      mixed.

PMID- 7570501
TI  - [Can electronic communication and computer networks improve monitoring of
      infectious diseases?].

PMID- 7570500
TI  - [Patient listing system--grouping of patients and workload of physicians.
      Patterns in general practice in the municipality of Trondheim].
AB  - To assess the impact of patient mix on general practitioners' work-load within a
      list patient system, a "key" was constructed for computing expected use of
      general practitioners' services by patients on a doctor's list. The key was based
      on empirically observed variations in consultation rates for different age and
      sex-groups. Computations were made for 90 general practitioners in Trondheim.
      Expected patient weight varied in accordance with the proportion of women and of
      old patients on the doctor's list. The mean expected use of consultations was
      approx. 6% higher for patients on female doctor's lists relative to patients on
      male doctors' lists. The difference between the patients of male and female
      doctors respectively was far less than previously expected. This is explained by
      the fact that female doctors - compared with their male colleagues - usually have
      more children and fewer old people on their list of patients.

PMID- 7570503
TI  - [Smoking cessation and aftercare].

PMID- 7570504
TI  - [Infectious diseases--new and old, in new forms].

PMID- 7570505
TI  - [Acupuncture against stroke?].

PMID- 7570502
TI  - [Idiopathic anteversion of the femur].

PMID- 7570506
TI  - [Bladder function in patients with spinal cord injuries].

PMID- 7570507
TI  - [Steroid receptors in breast cancer].

PMID- 7570508
TI  - [Estrogen receptor studies in breast cancer based on histological material.
      Correlation with results from needle biopsy aspirates and pS2 protein
      determination].
AB  - Oestrogen receptor analyzed in archive, histologic specimens from 57 breast
      cancers showed a concordance with determination in fresh material of 50 to 60%.
      This means that about half of the oestrogen receptor positive tumours are "lost"
      when using histologic specimens. pS2 protein is an indirect marker of a
      functioning oestrogen receptor and was demonstrated in 84% of the carcinomas,
      including 15 that were oestrogen receptor positive in cytologic material, but
      negative in histologic specimens. In cases where only histologic specimens are
      available for receptor analysis, additional determination of pS2 protein may be
      useful.

PMID- 7570510
TI  - [Bladder problems after traumatic spinal cord injuries].
AB  - Patients with a recent traumatic spinal cord lesion admitted consecutively to
      Sunnaas Rehabilitation Hospital during the five-year period from 1987 to 1991
      were included in a study of bladder function, including results of urodynamic
      investigation and urological complications, both during primary rehabilitation
      and on average five years (two to nine years) after injury. Indication for
      urodynamic investigation was found in 125 out of 170 patients. The study shows
      that micturition is a major problem after spinal cord injury, and that the follow
      up programme after the rehabilitation period should be improved. General
      practitioners should be aware of these problems. Close cooperation between the
      rehabilitation department and the primary health service is needed to avoid renal
      and urinary complications in these patients.

PMID- 7570511
TI  - [Children of psychiatric patients--what to do?].
AB  - Examination of the records of first admission patients at the acute ward of a
      psychiatric hospital indicated that contact was established with only 4% of the
      patients' children. A screening for assistance to patients' children at the acute
      wards of 21 hospitals showed, furthermore, that only one hospital offered such
      assistance as a routine. It is argued that this shows a relative neglect of a
      group (patients' children) with well documented mental health problems, whose
      only contact with the health services may be their parent's hospital, and whose
      problems may relate directly to the parent's problems.

PMID- 7570509
TI  - [Acupuncture therapy in stroke during the subacute phase. A randomized controlled
      trial].
AB  - The aim of this study was to investigate whether acupuncture treatment, if given
      to stroke patients in subacute phase in addition to rehabilitation would
      influence motor function, activity of daily living (ADL) and quality of life.
      After obtaining informed consent, 45 patients (median age 57 years) were
      randomised into a control group (n = 21) and an acupuncture group (n = 24).
      Median time from onset of stroke to inclusion in the study was 40 days. The
      inclusion criterion was hemiparesis following a first-ever stroke. When included
      and six weeks later all patients were evaluated by three measurement systems: the
      Motor Assessment Scale for stroke patients, Sunnaas Index of ADL and Nottingham
      Health Profile. All patients underwent individually adapted rehabilitation
      therapy. The patients in the treatment group were given classical acupuncture
      three to four times a week for six weeks, each session lasting 20-30 minutes.
      Both groups improved significantly in motor function and ADL. However,
      improvement was significantly greater among the acupuncture group than among the
      controls. Only the acupuncture group rated a significantly improved quality of
      life. Our results indicate that acupuncture gives an additive therapeutic benefit
      when given to stroke patients during their rehabilitation programme in the
      subacute phase.

PMID- 7570512
TI  - [The impact of psychological factors on the treatment of somatic diseases. The
      situation today, as exemplified by cardiovascular disorders and cancer].
AB  - Prospective intervention studies have shown that cognitive-behavioral
      interventions can improve morbidity and mortality both in cancer and in
      circulatory disorders. Research in fields like molecular biology,
      psychoneuroendocrinology and psychoneuroimmunology has identified some of the
      links between emotions and biological reactions. The paper reviews the situation
      today and concludes that psychobiologically based interventions may make
      important contributions to somatic medicine.

PMID- 7570513
TI  - [Microbiology and ecology--the microbe aspect].
AB  - Invisible microbes play very important roles in all ecosystems. Living generally
      in harsh and seemingly inhospitable places all around, they reveal a remarkable
      potential and resilience of life. In all microbial ecosystems, antimicrobial
      substances, as antibiotics, are of crucial regulatory importance. In modern human
      and veterinarian medicine, about 50 million kilos of potent antibiotics are used
      every year. Some of these substances are very persistent in the ecosystem, i.e.
      they remain in the natural environment for a very long time. Now the microbial
      empire is striking back, and increasing resistance towards antibiotics is
      becoming a global problem. The need for a proper future strategy is underlined.

PMID- 7570515
TI  - [Cystometry in neurogenic bladder disorders. Methodologic problems and assessment
      of risk of renal complications].
AB  - Patients with neurogenic bladder dysfunction may have an elevated detrusor
      pressure during the filling or emptying phase, which may result in upper urinary
      tract dysfunction. Cystometric examination is important in order to evaluate the
      risk of such complications and the effect of therapeutic intervention. If
      compliance is low, the cystometric filling rate has to be slow in order to obtain
      a physiologically representative pressure. In the case of detrusor hyperreflexia,
      intraindividual variation makes it necessary to perform repeated filling of the
      bladder in order to get representative values for the amplitude and duration of
      the detrusor contraction. The clinical significance of these methodological
      problems is discussed.

PMID- 7570514
TI  - [Communicable diseases in Norway. Epidemiological status and future challenge for
      prevention of the most important diseases].
AB  - The authors briefly review the incidence of some of the more important
      communicable diseases in Norway today. Thanks to extensive use of vaccines,
      effective preventive measures and useful antibiotics, many of these diseases are
      no longer a threat to public health, as was the rule up to the latter half of
      this century. However, constant vigilance is needed to sustain this positive
      situation.

PMID- 7570519
TI  - [Misuse by hospitals of positions for junior physicians].
AB  - In Norway, some positions for junior hospital doctors are designated for clinical
      research combined with routine clinical work. However, in this survey among 124
      doctors holding such positions at seven Norwegian university hospitals, only 35
      of 98 doctors (36%) were given sufficient time for clinical research. The survey
      demonstrates that heavy clinical work load, pressure for clinical "productivity"
      and limited economic resources are important obstacles to clinical research.

PMID- 7570516
TI  - [Antithrombotic therapy in cerebrovascular disorders].
AB  - Warfarin is recommended as primary prophylactic therapy for patients older than
      60 years with non-valvular atrial fibrillation and for patients with additional
      risk factors for thromboembolism. Warfarin should also be given as secondary
      prophylaxis. Patients with contraindications to warfarin should be given aspirin.
      Anticoagulant therapy is recommended against progressive ischemic stroke and in
      cardiogenic cerebral embolism, although conclusive evidence of the benefit is
      lacking. In the case of transient ischemic attacks and minor stroke, antiplatelet
      therapy reduces the risk of subsequent stroke by approximately 25 percent.
      Antiplatelet therapy is probably indicated in cases of acute, stable ischemic
      stroke.

PMID- 7570517
TI  - [Primary health care and emergency admission of patients. What happened prior to
      admissions and how did the patients experience the primary health care system?].
AB  - Of 238 patients admitted to Haugesund hospital, 159 completed a questionnaire
      evaluating the primary health care system and describing events before admission
      to hospital. Half of the patients had contacted the health care system within one
      hour after onset of symptoms. Two thirds of the 159 patients had consulted a
      general practitioner, while 33 patients had used the emergency telephone number
      or had gone directly to the hospital. Two thirds of the patients who had been
      examined by a general practitioner were visited within an hour after first
      contact. According to the questionnaires, 58 patients visited at home were sicker
      than the 62 patients examined at the doctor's surgery. No such difference was
      found, however, by the junior doctor who examined the patients upon admission to
      hospital. Apart from the 11 patients who felt rejected at their first contact
      with the health personnel, the patients judged this first contact with the
      primary health care system and the general practitioner to be very satisfactory.

PMID- 7570520
TI  - [Hospital infections as quality indicators. DRG-based financing, did it change
      therapeutic quality?].
AB  - In 1991, four Norwegian hospitals switched from 100% global budgeting to a
      combination of 40% DRG-based per case payment and 60% fixed grant financing. In
      order to monitor quality of care, the prevalences of infections acquired in
      hospital were registered in medical and surgical departments during the two first
      years after changing the system of financing. The total cumulative prevalence of
      hospital acquired infections was 6.3%. There was no change in the occurrence of
      hospital acquired infections during the observation period. The prevalence of
      nosocomial infection was significantly higher among patients receiving long-term
      care than among other patients (18.9% vc. 4.2%, p < 0.0001).

PMID- 7570518
TI  - [Emergency hospital admissions. A survey and consumer assessment of conditions in
      an emergency department admission office].
AB  - 159 patients admitted to a local hospital completed a questionnaire during the
      autumn of 1992 in order to evaluate the service rendered to the patients during
      their stay in the admission/emergency unit. The patients were generally satisfied
      with the service rendered in the admission/emergency unit. However, some patients
      were dissatisfied with the information given by the nurses and the doctors. 83 of
      the patients (57%) were examined by a doctor within 15 minutes after admission.
      Information about how long and why they had to wait increased the level of
      satisfaction among the patients who had to wait more than 15 minutes. With
      respect to the patients' rating of different skills among nurses and doctors,
      only 37% of the patients rated technical competence as the most important factor
      for the nursing profession, as opposed to 59% for the doctors. For both
      professions the ability to give information was rated as the second most
      important factor. Since the comments from the patients reflect parts of the
      service that can be changed, we believe such surveys can be of great value for
      the hospitals' efforts to improve the service provided.

PMID- 7570522
TI  - [Postpartum challenge--the reverse of the mother-child-friendly medal].

PMID- 7570523
TI  - [Use of data from the SINTEF-NIS for evaluation of therapeutic quality at
      Norwegian hospitals].

PMID- 7570524
TI  - [Physicians accused of homicine].

PMID- 7570521
TI  - [Myocardial infarction as indicator in a time study. DRG-based financing, did it
      change therapeutic quality?].
AB  - In Norway, four hospitals switched from 100% global budgeting to a combination of
      40% DRG-based per case payment and 60% fixed grant financing in 1991. In order to
      assess changes in the quality of care in acute medicine during the two first
      years after changing the system of financing, delays before initiation of
      thrombolytic therapy in patients with acute myocardial infarction were
      registered. The time from arrival in hospital to initiation of thrombolytic
      therapy was unchanged, median time was 50 minutes in the first registration
      period and 55 minutes in the second. 45% of the patients in the intensive care
      unit/coronary care unit with acute myocardial infarction received thrombolytic
      therapy.

PMID- 7570526
TI  - [Unhappy life in happy Sorland--a figurative use of official health data].

PMID- 7570525
TI  - [The length of medical studies and physicians' salaries].

PMID- 7570527
TI  - [ACE inhibitors, yes or no?].

PMID- 7570528
TI  - [Exhausted by life--or mysteriously ill?].

PMID- 7570529
TI  - [Postviral fatigue syndrome].
AB  - The post-viral fatigue syndrome occurs sporadically and in local outbreaks (Los
      Angeles, Akureyri, Royal Free Hospital). The clinical picture is marked by long
      lasting muscular fatigue directly following an acute infection. Other conditions
      associated with pronounced fatigue must be excluded. The diagnostic criteria set
      up by Centers for Disease Control (CDC) are the ones most commonly used.
      Aetiology and pathogenesis are unknown. Coxsackie B-virus seems to be associated
      with some cases at least. Immunological and endocrinological aberration,
      morphological changes in mitochondria and reduced cerebral blood perfusion have
      been demonstrated in some patients. There is no specific therapy. It is important
      for the patient that the symptoms be accepted by the doctor and society in
      general.

PMID- 7570530
TI  - [Does social support have an impact on the prognosis in cancer?].
AB  - Social support is a compound concept. It is being used about different aspects of
      social integration and about the support provided by people in a social network.
      Increasing research has been done on the effect of social support on malignant
      diseases. However, weaknesses in the methodology make it difficult to evaluate
      the results. For example, the concept of social support may not be adequately
      defined and the aspects of social support that are studied may be somewhat
      arbitrary. Both epidemiological research and studies on certain groups of
      patients support the idea that social support influences our health and our life
      expectancy. We have reviewed the existing literature on the impact of social
      support on malignant disease to find out if social support has proven to be of
      any prognostic value in the case of cancer.

PMID- 7570531
TI  - [Clozapine and myocarditis].
AB  - Drugs have different kinds of adverse effects, one of the most serious being
      myocarditis. This condition is usually reported as an incidental finding, but can
      also be fatal. The drug clozapine, available on the European market since the
      1970s, can cause myocarditis. This report describes the myocardial findings in a
      patient who died suddenly after taking increasing doses of clozapine. An allergic
      adverse reaction to clozapine is suspected. The immediate cause of death was an
      embolus of the central pulmonary artery.

PMID- 7570532
TI  - [Use of growth hormone during catabolic state in a patient in postoperative
      intensive care].
AB  - Patients in the intensive care unit often enter a catabolic state with
      significant protein loss, which may increase postoperative complications.
      Nutritional support alone usually does not reverse a catabolic state and thereby
      induce a positive protein balance. Recent studies suggest that recombinant human
      growth hormone (rhGH) stimulates protein synthesis and improves protein balance
      in critically ill patients. An increase in the level of growth hormone often
      fails to occur in critical illness and injury. We describe the case of a man aged
      45 years who underwent laparoscopic fundoplasty for hiatus hernia repair. Because
      of complications, including perforation of the oesophagus, he entered a sustained
      catabolic state with negative protein balance and a weight loss approaching 20%.
      Therefore, on the 29th day after operation we started treatment with rhGH,
      Norditropin 24 IE/day im. The protein balance became positive three days later.
      This parameter maintained positive, also after the growth hormone therapy was
      discontinued 12 days later. The further course was uneventful and the patient was
      transferred to his local hospital 51 days after the fundoplasty. His condition
      was improving steadily.

PMID- 7570533
TI  - [Accidental atropine poisoning. Anticholinergic syndrome in a child after
      intranasal overdose].
AB  - As paediatricians we are often reminded of the importance of correct marking and
      storage of drugs to prevent accidental intoxication. We report on a patient who
      developed typical signs of central and peripheral anticholinergic syndrome within
      a few hours after intake of atropine through her nose. Clinical presentation and
      treatment are described. Children with fever, Down's syndrome or convulsive
      disorders seem to be particularly sensitive to atropine.

PMID- 7570534
TI  - [New vaccines. What can we expect in the coming years?].
AB  - There is an urgent need for new vaccines. The biotechnological revolution has
      created new hope. However, developments are hampered by inadequate basic
      knowledge about the immunology of infections, and lack of coordination between
      public and commercial research and development work on vaccines. Recombinant
      vaccines are an important step forward when combined with new adjuvants, but the
      authorization of these adjuvants for use in humans has been slow. Recombinant
      live vectors for vaccine antigens circumvent this problem, but imply some risk in
      HIV-infected people. Nucleic acid vaccines are met with strong emotional
      resistance, because of many unanswered questions as to their safety. Mucosal
      vaccines make quality control simpler, open up for a safer use of live
      recombinant vectors and simplify delivery of the vaccine. New vaccines marketed
      in the last decade are surprisingly "old-fashioned". Traditional ways of making
      vaccines have still not been abandoned.

PMID- 7570535
TI  - [Blood transmission and infections].
AB  - A blood transfusion can never become a completely risk free event. Almost all
      kinds of infectious agents; viruses, bacteria and parasites, can be transmitted
      by blood. So far, hepatitis and HIV-infections have been focused. The state of
      readiness to meet these infections must be kept while we prepare for "new"
      agents, like parvovirus B19. Extensive international travelling will increase the
      possibility of blood-borne parasitic infections, like malaria and Chagas'
      disease, even with the very high quality demands imposed for Norwegian blood
      donors. We can keep a better eye on the infectivity of the blood products by
      strictly realizing our objective of national self-sufficiency. Recent research
      results indicate transfusion-mediated effects to the immune system, particularly
      of allogeneic transfusions containing leucocytes. This immunomodulation seems to
      enhance the risk of secondary infections. So far, it is impossible to tell
      whether this immunomodulation has any impact on the long-term outcome of
      malignant diseases. A blood transfusion will always represent a risk, although
      small, to the patient. This recognition makes it essential to carefully consider
      whether to give a patient a transfusion, and to document this decision properly.

PMID- 7570536
TI  - [ACE inhibitors and early diabetic nephropathy].
AB  - At present we are able to disclose diabetic nephropathy in the very early stages,
      i.e. when urinary albumin excretion is only slightly increased (20-200
      micrograms/min = microalbuminuria). Good blood glucose control and active
      antihypertensive treatment may stop or retard the further development towards
      renal failure. Angiotensin-converting-enzyme (ACE)-inhibitors seem to have a
      renoprotective effect. In this article we suggest guidelines for the use of ACE
      inhibitors in patients with type 1 diabetes and early diabetic nephropathy.
      Special concerns are included in respect of adolescents, pregnant women and
      persons with type 2 diabetes.

PMID- 7570537
TI  - [Chronic fatigue syndrome--a review of the literature].
AB  - Chronic fatigue syndrome is a clinical condition characterized by abnormal
      fatigue, subfebrile body temperature, sore throat, lymphadenopathy, arthralgia,
      myalgia and neuropsychiatric symptoms. Typically, the syndrome develops after a
      flu-like illness and is markedly exacerbated by exercise. The etiology is unknown
      and there is no single diagnostic test. The patients may have cognitive
      dysfunction, immunological and endocrinological abnormalities and abnormal
      mitochondria. Magnetic resonance imaging scans may show increased uptake of
      signals in the brain, and single photon emission computerized tomography reveals
      regional hypoperfusion of the brain. The author discusses similarities and
      distinctions between the syndrome and depression.

PMID- 7570541
TI  - [Physicians too protest against nuclear weapon testing].

PMID- 7570538
TI  - [Health and living conditions in the Agder counties].
AB  - The counties of Aust-Agder and Vest-Agder in southern Norway are often regarded
      as comprising a region where people can lead a good and easy life. However, a
      local statistical report published in 1993 demonstrated negative trends in these
      counties when compared with other parts of the country in regard to variables
      related to health and living conditions: Mortality before the age of 65, infant
      mortality, suicide among young people, cancer, use of tranquilizers and
      hypnotics, need for social security benefit, unemployment, average income, and
      Gross Regional Product per inhabitant. The report was a result of cooperation
      between different local and regional authorities. Following its publication, a
      new public consciousness seems to have emerged concerning the special problems
      experienced in Agder. Many questions have been raised, which can only be answered
      by further research.

PMID- 7570539
TI  - [Osteoporosis drugs prescribed on blue forms!].
AB  - The National Insurance Administration, through the system of blue prescription
      forms, refunds part of the cost of drugs used to treat a number of chronic
      diseases. To obtain a refund, the indication for prescribing the drug must be
      included in the list of diagnoses which entitle a refund through the system. The
      list is a long one, and costs are refunded for prophylactic drugs (e.g. against
      hypertension and hypercholesterolemia), drugs to alleviate symptoms (e.g. for
      certain skin diseases and heart failure) and curative measures. The qualitative
      criteria for a refund, over and above the diagnosis, are not precisely defined,
      and doctors are free to choose the drug they prefer, regardless of price. The
      authors discuss whether the list of diagnoses should be extended to include
      osteoporosis, and recommend that doctors should be able to prescribe the relevant
      preventive and palliative drugs on a blue form. Many think that this refund
      system is a good initiative.

PMID- 7570540
TI  - [Treatment of hypertension--change to the expensive!].

PMID- 7570542
TI  - [Physicians liable for military service for sale].

PMID- 7570545
TI  - [A case of sudden death among fattening pigs].
AB  - The sudden death of fattening pigs weighing about 60 kg is described. The animals
      had not previously shown signs of illness. Fusarium toxins were detected in the
      feed, albeit in small amounts. Mycotoxins are probably the cause of death.

PMID- 7570546
TI  - [The polymerase chain reaction (PCR)].

PMID- 7570544
TI  - [Selenium deficiency without clinical symptoms in young cattle on a dairy farm].
AB  - On a dairy farm a selenium deficiency was diagnosed on the basis of the blood
      chemistry of heifer calves. Of ten heifers, aged five to fourteen months, six
      animals had a glutathione peroxidase (GSH-PX) activity lower than 10 U/gHb. A
      good correlation was found between this low GSH-Px-activity and the selenium
      concentration in the blood. The animals had no symptoms of selenium deficiency
      nor elevated CPK levels. On the basis of the vitamin E-concentration in the blood
      it is postulated that the lack of symptom is mainly caused by the amount of
      vitamin E in the ration (grass and grass silage).

PMID- 7570543
TI  - [The dairying veterinary approach to a high bulk milk cell count caused by
      Streptococcus agalactiae].
AB  - The herd health approach for dairy herds with a high bulk milk somatic cell
      count, in which Streptococcus agalactiae plays a major role, was evaluated. After
      introduction of the standard mastitis prevention programme, all quarters of
      infected cows were treated during lactation. In three of the four herds
      investigated, the bulk milk somatic cell count dropped below the limit of 400,000
      cells/ml for a long period of time. The herd in which there were many infections
      with Staphylococcus aureus and Streptococcus agalactiae was an exception. The
      management, somatic cell count, and prevalence of subclinical mastitis in the
      different herds is discussed. It is concluded that for infection with
      Streptococcus agalactiae at the herd level, treatment during lactation can be an
      effective method to lower the bulk milk somatic cell count. In essence, however,
      the approach to the problem lies in the standard mastitis prevention programme.

PMID- 7570547
TI  - [Administration Day 1995.'Veterinarian has a practical approach to problems of
      conscience' and 'KNMvD (Royal Dutch Society for Veterinary Medicine) not slow,
      but members are'].

PMID- 7570548
TI  - [The KNMvD (Royal Dutch Society for Veterinary Medicine) and the certification of
      veterinary practice].

PMID- 7570549
TI  - [Well-being--intrinsic value--integrity. Developments in the reevaluation of the
      domesticated animal].
AB  - Owing to selective breeding and conditioning to husbandry methods, domestication
      has resulted in modification of the anatomy, physiology, and behaviour of
      animals. Nevertheless, domestic animals cannot be regarded and treated as
      artificial products. Public interest and concern about the welfare of domestic
      animals has led to the recognition of the intrinsic value of animals and, in
      extension of this, to the ethical principle of respect for the integrity of
      animals. The sensibility and acceptance of these principles by those involved in
      ethical decision-making depends on their fundamental views about humans and the
      living world. In order to make judgements about the use of, and interference
      with, animals, it is desirable to clarify these personal views. The principle of
      respect for the integrity of animals leads to considerations and arguments beyond
      animal health and welfare. This is shown by three examples: declawing of cats,
      caesarean section in cattle, and laying hens in battery cages.

PMID- 7570550
TI  - [Presentations from the symposium of June 22, 1995 'The Netherlands on the road
      to IBR-free status'. IBR, an underestimated problem].

PMID- 7570551
TI  - [The financial consequences of tolerating or controlling IBR].

PMID- 7570552
TI  - [Value of vaccines in the eradication of infectious animal diseases].

PMID- 7570553
TI  - [Principles of IBR marker vaccines].

PMID- 7570554
TI  - [IBR control with the European Union].

PMID- 7570556
TI  - [Value of the IBR-free certificate].

PMID- 7570557
TI  - [The marching route to an IBR-free status].

PMID- 7570555
TI  - [Results of Aujeszky disease control using marker vaccines].

PMID- 7570559
TI  - [Chloramphenicol in slaughter animals].

PMID- 7570558
TI  - [Pioneers: veterinarians from earlier times (11). Jacques de Solleysel II].

PMID- 7570560
TI  - [Foot and mouth disease].

PMID- 7570561
TI  - [Regulations animal transport further formulated. Transportation of impaired
      cattle].

PMID- 7570565
TI  - Use of the internal mammary artery as a graft in emergency coronary artery bypass
      grafting after failed PTCA.
AB  - The use of the internal mammary artery (IMA) is recommended in elective aorto
      coronary bypass grafting (CABG) because of favourable long-term patency results.
      In emergency CABG many surgeons prefer revascularization only with venous grafts
      due to the shorter operation time and higher initial flow rates of this type of
      graft. We investigated whether use of the IMA influences operative and mid-term
      results of emergency CABG after failed percutaneous transluminal coronary
      angioplasty (PTCA). From January 1990, to March, 1993, 56 emergency CABGs were
      performed in patients from 7 different cardiological centres where PTCA had
      failed. In 23 patients (Group A), the IMA was used as a bypass graft. In most of
      these patients the left IMA was anastomosed with the left anterior descending
      artery (n = 19). In one case both IMAs were used as bypass grafts. Venous grafts
      only were applied in 33 patients (Group B). Due to preparation of the IMA, aortic
      cross-clamp and bypass times were approximately 15 mins longer in Group A
      patients, although there was no significant difference in the number of grafts
      (1.7 +/- 0.8 in Group A vs. 1.5 +/- 0.7 in Group B). All patients of Groups A and
      B underwent echocardiographical investigations 14.6 +/- 8.2 months
      postoperatively. The overall mortality in Group A was 13% (n = 3) compared to 9%
      (n = 3) in Group B (p = 0.58). Significant predictors for death were age 65 years
      and over, diabetes mellitus, dilatation of the RCX and stenoses unfavourable for
      PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570564
TI  - Operative risk assessment in coronary artery bypass surgery, 1990-1993:
      evaluation of perioperative variables.
AB  - Patient characteristics and the results of cardiac surgery change with time. To
      achieve the best possible treatment a continual analysis of results is necessary.
      The present study analyzes 1225 consecutive patients undergoing isolated
      aortocoronary bypass surgery for the four-year period ending September 1993.
      Average age was 63 years (range 32-86 years), 927 (75.7%) patients were male and
      298 (24.3%) were female. Hospital mortality was 2.2% (17/787) for elective
      surgery, 6.3% (21/336) for urgent surgery, and 9.8% (8/82) for emergency surgery.
      Intraoperative variables increasing independently operative mortality as
      evidenced by multivariate analysis were the following: prolonged aortic cross
      clamping time (p < 0.0001), absence of cold-blood cardioplegia (p = 0.0012),
      absence of bilateral use of internal mammary artery (p = 0.0035). Likewise,
      intraoperative variables influencing major adverse outcome (operative mortality
      and/or need for intra-aortic balloon pulsation) were the following: prolonged
      aortic cross-clamping time (p < 0.0001), absence of cold-blood cardioplegia (p =
      0.0360). In conclusion, global ischemic time was the dominant variable in
      predicting operative outcome. Furthermore, a protective effect of cold blood
      cardioplegia and bilateral internal mammary artery grafting was evidenced.

PMID- 7570562
TI  - Isotonic versus hypertonic initial hyperkalemic reperfusion after cardioplegic
      arrest in isolated hearts.
AB  - In 24 isolated perfused guinea-pig hearts, 40 min of hyperkalemic arrest and
      ischemia at 37 degrees C were followed by 5 min of either isotonic or hypertonic
      initial hyperkalemic reperfusion (HKR). Hearts were divided into 3 groups: HKR, 5
      min initial reperfusion with isotonic hyperkalemic Krebs' solution; Mannitol,
      initial reperfusion with hypertonic (450 mosm fur 1 min and 330 mosm for 4 more
      min) hyperkalemic Krebs' solution modified by addition of mannitol; NaCl, same as
      Mannitol group but using NaCl instead of mannitol to increase osmolarity. In
      isotonic HKR hearts, postischemic peak reflow was 98 +/- 11% of pre-ischemic
      control. Subsequently coronary flow stabilized at 75% of control. Left
      ventricular developed pressure (LVDP) recovered to 60% of control. Hypertonic
      reperfusion increased peak reflow to 141 +/- 11% in the mannitol and to 121 +/-
      12% in the NaCl groups, but had no effect on the subsequent reduction of coronary
      flow to 75% of control. Recovery of LVDP, dP/dtmax, dP/dtmin, the time constant
      of relaxation, and O2 consumption did not differ between groups. Postischemic
      flow responses to adenosine, acetylcholine, and nitroprusside were equivalently
      reduced in all groups. We conclude that the flow increase seen in the hypertonic
      reperfusion model of the study may be due to direct coronary vasodilation rather
      than the desired reduction of endothelial or perivascular cell edema by the
      hypertonic solutions.

PMID- 7570566
TI  - Risk factors of reoperations for prosthetic heart valve dysfunction in the ten
      years 1984-1993.
AB  - From January 1984 to December 1993 a total of 154 patients (89 men and 85 women)
      required 160 reoperations for prosthetic heart valve dysfunction. Four patients
      required a second, two patients a third reoperation. Age was (mean +/- SD
      [range]) 38.8 +/- 10.2 (17 to 64) years. The primary operation was mitral valve
      replacement in 105 patients, aortic valve replacement in 20, and both aortic and
      mitral valve replacement in 29. The time interval between initial valve
      replacement and reoperation was 66.4 +/- 40 (3 to 288) months for the mechanical
      prostheses and 68.7 +/- 32 (24 to 140) months for bioprostheses; the difference
      was not statistically significant. Primary tissue failure was the most common
      cause of the reoperation for bioprostheses and valve thrombosis for mechanical
      prostheses. The hospital mortality rate was significantly higher in the
      replacement of mechanical prostheses (14/58 = 24.1% vs. 7/102 = 6.8%, p = 0.004).
      Low preoperative functional capacity and valve thrombosis were linked to higher
      mortality rates. It is discussed that monoleaflet mechanical valves yielded the
      highest operative mortality and that, excluding these, the risk of mortality in
      prosthetic valve reoperations today does not differ much from that in primary
      valve replacements.

PMID- 7570563
TI  - The intraaortic balloon pump for postcardiotomy heart failure. Experience with
      169 intraaortic balloon pumps.
AB  - The intraaortic balloon pump (IABP) is usually the first mechanical device
      inserted for perioperative heart failure. In the present study we have reviewed
      our experience with 169 IABP insertions with emphasis on IABP complications,
      route of insertion, and identification of predictors of mortality. Between
      January 1, 1984 and March 31, 1993 3,591 adult patients underwent cardiac
      surgical procedures, 169 of whom (4.7%) had an IABP inserted preoperatively (7
      patients, 4.1%), intraoperatively (109 patients, 64.5%), or postoperatively (53
      patients, 31.4%). There were 137 men (81.1%) and the mean age was 60.2 +/- 8.8
      years (28-78 years). Operations included 149 coronary bypass grafting (CABG)
      (4.6%, 149/3,209), 6 valve replacements, single or double (2.4%, 6/255), and 14
      valves combined with CABG (11.0%, 14/127). The IABP was used more frequently in
      reoperations (14.8%, 80/542), compared to primary operations (2.9%, 89/3,049), p
      < 0.001. It was also more frequently used after emergency operations (50.7%,
      39/77), than after elective operations (3.7%, 130/3,514), p < 0.001. In 119
      patients femoral insertion was performed (13 percutaneously and 106 surgically),
      while 50 patients had an intraaortic insertion. The mean duration of IABP support
      was 50 hours (0.5-576 hours). There were 8 (4.7%) complications related to the
      balloon pump, all after femoral insertion (3 after transcutaneous and 5 after
      surgical insertions). Six of the complications occurred when the IABP was
      inserted intraoperatively and 2 postoperatively. The complications were 7 cases
      of leg ischemia (88%) and 1 groin wound infection.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7570571
TI  - Two-stage bronchoplasty for synchronous contralateral lung cancers.
AB  - A 62-year-old male with two synchronous squamous-cell carcinoma was successfully
      treated in two stages by right upper sleeve lobectomy and left S6 sleeve
      segmentectomy. The patient remains well without recurrence two years after
      surgery. Bronchoplastic surgery is an effective approach for multicentric hilar
      cancers with poor pulmonary function.

PMID- 7570572
TI  - Pulmonary metastasis of polymorphous low-grade adenocarcinoma of the minor
      salivary gland.
AB  - A surgical case of pulmonary metastases of polymorphous low-grade adenocarcinoma
      (PLGA) originating from the minor salivary gland in the soft palate in a 62-year
      old woman is reported. PLGA has been to be a locally invasive carcinoma without
      distant metastases; thus our case is the first reported case with histologically
      proven distant metastases to the lung. We emphasise that attention should be paid
      to distant metastases especially to the lung even in case of PLGA.

PMID- 7570570
TI  - Intrathoracic transposition of the musculocutaneous flap in treating empyema.
AB  - Intrathoracic transposition of the musculocutaneous (MC) flaps of the latissimus
      dorsi and rectus abdominis was performed after open-drainage thoracotomy in 6
      patients with empyema. The MC flaps were designed in such a way that the muscle
      bearing skin paddle was extended well beyond the distal muscle borders. The MC
      flaps thus provided substantially larger pieces compared to muscle flaps. With
      the exception of one patient with persistent bronchopleural fistula whose empyema
      recurred due to the reopening of the fistula, the thoracic closure was successful
      in all patients. Postoperative magnetic resonance imaging revealed a well
      preserved volume of subcutaneous tissue in the flaps, while the muscle portions
      of the flaps had atrophied. In conclusion, compared to muscle flaps, MC flaps
      have the advantages that (1) larger empyema cavities can be obliterated, and (2)
      the deformity of the thoracic wall can be minimized because of the small range of
      resected rib segments and well-preserved volume of subcutaneous tissue in the
      flap long after the transposition. The use of MC flaps is thus indicated for the
      empyema cavity remaining when a cavity is cleaned up of granulatous tissue with
      eradication of bronchopleural fistula.

PMID- 7570568
TI  - Surgery for cavoatrial extension of malignant tumors.
AB  - Surgical management for cavoatrial involvement of malignant tumors and its
      outcome is reported on for 6 patients; their age ranged from 55 to 79 years and 5
      were male and 1 female. The basic disease was renal cell carcinoma in 5 cases and
      adrenal leiomyosarcoma in 1. Intracaval tumor extension was diagnosed by computed
      tomography, magnet resonance imaging, digital subtraction angiography, and
      echocardiography. The tumor was resected together with adherant vena cava and
      invaded right-atrial wall, using cardiopulmonary bypass and normo- or mild
      hypothermia in 5 patients. The caval defect needed to be reconstructed with a
      slit GORE-TEX vascular prosthesis in 3 patients. In all patients the tumor
      resections were successful and without major complications. All patients survived
      and are well from 4 to 52 months after the surgery. It is concluded that such
      cavoatrial extensions of malignant tumors can be safely and accurately resected
      with the aid of cardiopulmonary bypass, with favorable early and late outcomes in
      patients who have no distant metastatic lesions.

PMID- 7570567
TI  - The efficacy of amrinone or adrenaline on low cardiac output following
      cardiopulmonary bypass in patients with coronary artery disease undergoing
      preoperative beta-blockade.
AB  - We examined 20 patients undergoing coronary bypass grafting for coronary artery
      disease with NYHA classifications of II and III who had been treated with beta
      blocking agents. Patients were randomised for administration of either adrenaline
      (0.1 microgram/kg/min) or amrinone (bolus 1 mg/kg, continuous infusion of 5-10
      micrograms/kg/min), if following cardiopulmonary bypass their cardiac index was <
      2.4 L/min/m2 with normal peripheral resistance and normal or increased right- or
      left-ventricular filling pressures. Over a period of 1 hour, the hemodynamic
      parameters mean arterial pressure (MAP), cardiac index (CI), heart rate (HR),
      coronary perfusion pressure (CPP), total peripheral resistance (TPR), as well as
      the pressure-work index (PWI) were registered or calculated. By means of a
      coronary sinus catheter myocardial arterio-venous oxygen content difference
      (AVDO2cor), myocardial blood flow (MBF), using the thermodilution method, and
      myocardial oxygen consumption (MVO2) could be measured or calculated.
      Simultaneously, arterial and myocardial lactate concentrations and, using the
      arterio-venous lactate ratio, myocardial lactate extraction or production were
      quantified. Using a transseptal approach, the left-ventricular pressure curve was
      measured and used to differentiate for myocardial contractility (dp/dtmax).
      Following induction of anesthesia and after cardiopulmonary bypass, plasma levels
      of the used beta-blocking agent were determined. Both substances caused a
      significant increase in myocardial contractility, with adrenaline showing a more
      potent effect than amrinone. Both substances caused a significant increase in CI
      with a mild increase in HR. Amrinone caused a significant drop in TPR, while MAP
      remained practically constant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570569
TI  - Recovery of intraoperatively shed blood in aortoiliac surgery: comparison of cell
      washing with simple filtration.
AB  - To regain blood shed intraoperatively, two different systems are clinically
      established: washing and centrifuging red blood cells to produce autologous
      erythrocyte concentrates and devices for immediate reinfusion of whole blood
      after mere filtration. In a prospective-randomised study to compare both methods
      regarding their efficiency, adverse effects, and economy, 20 patients of our
      department undergoing elective aortoiliac surgery received intraoperative
      autotransfusion by means of either cell-washing (CS) or salvage of whole blood
      (WB). Patients were preoperatively randomized into one of the two groups and were
      evaluated with respect to standard metabolic and haematological laboratory
      parameters preoperatively, during surgery, after transfer into the recovery room,
      24 h after surgery, after transfer into the recovery room, 24 h after surgery,
      and at discharge. Both patient groups were well comparable in demographics,
      preoperative laboratory data, and indication for operation. Handling was easier,
      the set-up time was shorter with the whole blood filtration device (10.2 +/- 2.3
      versus 21 +/- 1.9 min, p = 0.0023), and no additional personnel was needed to run
      the system. The whole blood device also allowed a greater percentage of aspirated
      blood to be returned intraoperatively compared to cell washing (73.5% +/- 7.2
      versus 51.1% +/- 6.5, p = 0.03). Thrombocytopenia occurred in 7 (CS) and 3 (WB)
      patients intraoperatively with a significant difference in platelet count between
      the two groups (118 +/- 17 [CS] versus 170 +/- 12 [WB]*10(9)/L, p = 0.025).
      Expected changes in the perioperative course of the clotting parameters such as
      highly increased PTT levels and moderately prolonged prothrombin times occurred
      in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570575
TI  - Establishment and characterization of two clonal cell lines derived from murine
      mandibular condyles.
AB  - We have established two clonal cell lines, designated SM1/9 and SM25/3 from the
      mandibular condyles of newborn BALB/c mice by immortalization with the SV40 large
      T antigen. These cells have a high proliferative activity and have been
      maintained in culture for over 50 passages. They are polygonal in shape. Electron
      microscopic studies indicate an immature phenotype for both clones and a lack of
      prominent intracellular filaments typical of fibroblasts. SM25/3 demonstrates
      different biological properties as compared to SM1/9, it is tumourigenic in nude
      mice, has a faster growth rate and exhibits less differentiated features. Both
      cell lines have low constitutive levels of alkaline phosphatase, and the activity
      of this enzyme is increased significantly in a dose and confluency dependent
      manner by retinoic acid and 1,25 (OH)2 vitamin D3. The cells express transcripts
      for retinoic acid receptors mRAR-alpha and mRAR-gamma but not for mRAR-beta. They
      also express mRNA for the 1,25 (OH)2 vitamin D3 receptor. They co-express
      transcripts for collagen types I, II, III. Expression of mRNA for extracellular
      matrix proteins such as biglycan, osteopontin, PAI-1 is detected. Cultured cells
      do not express mRNA for osteocalcin and this transcript is not inducible with
      1,25 (OH)2 vitamin D3 or retinoic acid. Chondrocyte markers such as link protein
      and aggrecan are not detected. In vitro assays indicate that the cell lines have
      a limited capacity for osteogenic or chondrogenic differentiation. Similarly
      agarose culture experiments and extended treatment with retinoic acid indicate
      that they do not resemble dedifferentiated chondrocytes. Both the cell lines
      appear to express a phenotype intermediate to osteoblasts and chondroblasts and
      possibly represent transitional differentiation stages of the progenitor cells of
      the mandibular condyle. These cells could serve as useful models in elucidating
      the pathways of early mesenchymal cell differentiation.

PMID- 7570576
TI  - Stratified squamous epithelia produce mucin-like glycoproteins.
AB  - The stratified squamous epithelia of the ocular surface, larynx, and vagina are
      mucus-coated epithelia, apices of which are subject to abrasive pressure from
      epithelia-epithelia interactions from eyelid, vocal cords, or vaginal folds,
      respectively. Mucus coats on these epithelia have generally been considered to be
      derived from the specialized mucin-producing cells embedded either in the
      epithelia or in adjacent tissues. Here we report the isolation, partial
      characterization, and cellular localization of a mucin-like glycoprotein produced
      by these stratified epithelia. In all three epithelia, the mucin-like molecule is
      present on cytoplasmic vesicles in subapical cells. As cells differentiate to
      their apical-most position adjacent to their mucus coat, the mucin-like molecule
      moves to the cell membrane where it is particularly prominent on microplicae
      folds. Lectin affinity chromatography was used to isolate the molecule from rat
      vaginal and corneal epithelium. Isolated material was approximately 60%
      carbohydrate and 40% protein. The major monosaccharide was N-acetylgalactosamine
      with lesser amounts of N-acetylglucosamine, galactose, mannose, xylose and
      fucose. Amino acid analysis demonstrated the predominant amino acids to be
      glycine, serine, threonine and proline. These data plus PAS and Alcian blue
      binding to the isolate indicate a mucin-like glycoprotein.

PMID- 7570574
TI  - Recognition of a 170 kD protein in mammalian Golgi complexes by an antibody
      against malarial intraerythrocytic lamellae.
AB  - Human erythrocytes infected with the malarial parasite Plasmodium falciparum
      contain flattened membrane lamellae. It has been suggested that the lamellae may
      be involved in the sorting of malarial proteins to the cytoplasm and the cell
      membrane of the host erythrocyte. We have previously shown that the lamellae
      accumulate sphingolipids by virtue of their lipid composition in a manner similar
      to the trans-Golgi and the trans-Golgi network in mammalian cells. In this paper,
      we show by immunofluorescence microscopy that a monoclonal antibody to the
      lamellae labeled a perinuclear organelle that colocalized with WGA and the
      mannose-6-phosphate receptor in cultured mammalian cells. Immunoelectron
      microscopy experiments revealed that LWLI labels cisternae of the trans-face and
      the trans-Golgi network. Western blot analysis of subcellular fractions using
      LWLI detected a 170 kD protein which is associated with the luminal side of Golgi
      membranes of rat liver and is conserved in all cell lines studied. Our results
      indicate that (i) the 170 kD protein is a novel marker of the mammalian trans
      Golgi and the trans-Golgi network and (ii) in addition to similarities in their
      morphological and lipid characteristics, the lamellae induced by P. falciparum in
      erythrocytes share proteinaceous determinants with the Golgi apparatus of
      mammalian cells.

PMID- 7570577
TI  - Lymphoid tissue in the kidney of the musk shrew, Suncus murinus.
AB  - We describe a lymphoid tissue in the kidney of the musk shrew, Suncus murinus. An
      anatomically well organised lymphoid tissue, resembling the mucosa-associated
      lymphoid tissue, is associated with the epithelium of the renal pelvis and the
      ureter, respectively. Lymphoid tissue distributed along the arcuate artery and
      arcuate vein is not structurally organised in centre and periphery. This tissue
      type is most prominently developed between blood vessels. Immunocytochemistry
      revealed S-100-immunoreactive dendritic cells in both, structurally organised and
      structurally non-organised lymphoid tissues. The lymphoid tissue is innervated by
      neurofilament-immunoreactive nerve fibres. Some of these nerve fibres are
      associated with glial fibrillary acidic protein-immunoreactive structures,
      indicating that they are myelinated.

PMID- 7570573
TI  - Cardiac surgery in Germany during 1994. A report by the German Society for
      Thoracic and Cardiovascular Surgery.

PMID- 7570578
TI  - Immunocytochemical colocalizations of serotonin, aromatic L-amino acid
      decarboxylase and polypeptide hormones in A- and PP-cells of the chicken
      endocrine pancreas.
AB  - The colocalization of serotonin and aromatic L-amino acid decarboxylase (AADC) in
      the avian pancreatic polypeptide-containing PP-cells and glucagon-storing A-cells
      of the chicken endocrine pancreas was investigated using combined pre-embedding
      immuno-peroxidase and post-embedding immunogold electron microscopic
      immunocytochemistry. The avian pancreatic polypeptide-immunoreactive cells
      manifested by the labeling of immunogold particles on secretory granules were
      also immunoreactive with antisera directed against serotonin and AADC, an enzyme
      involved in the synthesis of serotonin. In PP-cells immunoreactivity against the
      anti-serotonin serum was stronger in secretory granules than in the cytoplasmic
      matrix, whereas immunoreaction with the anti-AADC serum was observed to be more
      intense in the cytoplasmic matrix. Immunoreactions with the serotonin and AADC
      antisera were also found in secretory granules of glucagon-storing A-cells. These
      results indicate that serotonin is co-stored within secretory granules of both A-
      and PP-cells, and that AADC is localized within secretory granules of A-cells,
      and may be present in the cytoplasmic matrix of PP-cells. It is probable that
      serotonin is synthesized and released simultaneously with secretory granules from
      both A- and PP-cells of the chicken endocrine pancreas.

PMID- 7570580
TI  - A simple maneuver in follow-up digital subtraction angiography for multiple
      coronary-aorta bypass grafts.
AB  - A simple maneuver in intraarterial digital subtraction angiography (DSA) is
      proposed to improve the images of left internal thoracic artery bypass grafts
      (LITAGs). A contrast flush in the left subclavian artery, using a catheter that
      had been percutaneously introduced from the left brachial artery, was carried out
      in 14 patients with multiple coronary-aorta bypass grafts (CABGs) after aortic
      DSA. The side-hole portion of the catheter tip was positioned in the proximal
      left subclavian artery as the coiled portion remained in the aortic arch.
      Nonionic contrast medium (350 mg/ml of iodine) was injected with an automatic
      injector in a volume of 6-8 ml and at a flow rate of 3-4 ml/sec. Left subclavian
      arterial flush DSA delineated the LITAGs excellently in 11, well in 3, and fairly
      or poorly in none of the 14 cases. There were no complications in any of these
      cases. A supplemental contrast flush of the left subclavian artery with a pigtail
      catheter following aortic DSA improves the diagnosis of multiple CABG patency.

PMID- 7570579
TI  - Assessment of tissue integrity, ultrastructure and steroidogenic activity of
      corpora lutea of the marmoset monkey, Callithrix jacchus, following in vitro
      microdialysis.
AB  - Microdialysis of marmoset (Callithrix jacchus) corpora lutea in vitro was
      evaluated regarding morphology, activity of 3 beta-hydroxysteroid-dehydrogenase
      (3 beta-HSD) and progesterone (P) secretion. Two different dialysis media were
      used: an unbuffered ringer solution and Krebs-Henseleit buffer gassed with
      carbogenium. Additionally, the effects of the luteotrophin prostaglandin E2
      (PGE2) on P secretion were examined for both media. In general 3 zones of tissue
      according to the maintenance of cellular integrity could be identified after
      dialysis. Structurally intact cells were found in close vicinity to the dialysis
      tubing or the bathing medium after 8 h of perfusion. These 2 zones were separated
      by a sheet of cells which showed signs of ischemic injury and whose activity of 3
      beta-HSD was reduced. During dialysis with ringer solution P release stayed
      constantly high for a longer period of time than with Krebs buffer. With both
      media PGE2 stimulated P release but could not prevent the decrease in P
      production during dialysis with Krebs buffer. In general profiles of baseline
      secretion, were more stable after treatment than for untreated corpora lutea.
      There, under dialysis with ringer solution, the ultrastructure of cells close to
      the dialysis tubing was well preserved exhibiting euchromatic nuclei, tubular sER
      and numerous mitochondria gathered in the perinuclear region. In contrast, with
      Krebs buffer heterochromatization of nuclei and vesiculation of smooth
      endoplasmic reticulum prevailed. After application of PGE2 no histological and
      ultrastructural differences could be found between tissue dialysed with ringer or
      Krebs buffer. In these specimens the sER of zone A cells generally appeared
      vesiculated. Our results indicate (1) a close structure-function relationship of
      luteal cells in the tested system, (2) the suitability of the system to study
      intra-luteal regulation and (3) the necessity to control structural integrity of
      the dialysed tissue.

PMID- 7570581
TI  - Evidence for the presence of two amino-terminal isoforms of neurofibromin, a gene
      product responsible for neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder, primarily
      affecting cells of neural crest origin, and is characterized by cafe-au-lait skin
      spots, multiple neurofibromas, and higher incidence of malignancy. A gene linked
      to NF1 encodes neurofibromin, an established function of which is to stimulate
      intrinsic GTPase activity of ras protein. The neurofibromin gene gives rise to
      multiple transcripts generated by alternative splicing, that encode various
      neurofibromin isoforms. In this study, we have cloned a cDNA encoding a newly
      identified species of a putative amino-terminal isoform which lacks a large
      portion of neurofibromin, including the domain related to GTPase-activating
      protein. This clone carries the insert of 2.7 kb, coding for a protein of 593
      amino acid residues, tentatively termed N-isoform 11, whose amino-terminal 574
      residues are identical to those of authentic neurofibromin encoded by the eleven
      exons located at the 5' portion of the gene. Previously, we cloned a cDNA coding
      for a similar isoform of 551 amino acid residues, termed N-isoform 10, whose
      amino-terminal portion is encoded by the first ten exons. The molecular weights
      of these two deduced N-isoforms are consistent with the values determined by in
      vitro translation of the mRNA transcribed from each N-isoform cDNA. The presence
      of the amino-terminal isoform(s) suggests the physiological significance of the
      amino-terminal portion of neurofibromin.

PMID- 7570582
TI  - Antibiotic susceptibility of the sputum pathogens and throat swab pathogens
      isolated from the patients undergoing treatment in twenty-one private clinics in
      Japan.
AB  - Bacteriology of the respiratory isolates from 2,539 patients with respiratory
      infections in 21 primary care clinics was documented. Of a total of 1,887 strains
      of potential pathogens recovered from 1,507 patients, 996 were gram-positive and
      891 were gram-negative. Major pathogens were Staphylococcus aureus, Haemophilus
      influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. The MIC's
      against microbial isolates of six antimicrobial agents were determined.
      Ciprofloxacin and ofloxacin were more active against S. aureus, Moraxella
      catarrhalis and Pseudomonas aeruginosa, and ampicillin and cefteram were more
      active against S. pnuemoniae and S. pyogenes than four other antimicrobials
      tested, respectively, in this experiment. New quinolones and new generation
      cephems were active against H. influenzae and Enterobacteriaceae. Only one strain
      of S. aureus was methicillin-resistant. As regards other pathogens, 6.5% of S.
      pneumoniae and 14.9% of H. influenzae were resistant to ampicillin, and 26.7% of
      H. influenzae were beta-lactamase-positive. MRSA was found infrequently. But
      ampicillin-resistant S. pneumoniae and H. influenzae were found in primary care
      clinics almost as frequently as in intensive-medication-oriented clinics.

PMID- 7570583
TI  - T1 measurements with clinical MR units.
AB  - To improve accuracy and feasibility of the proton spin-lattice relaxation time
      (T1) measurements in routine Magnetic Resonance Imaging (MRI), a phantom with
      polyvinyl alcohol gels and gadrinium diethylene triamine pentaacetic acid
      solutions was imaged with 1.5T clinical MR units and T1s were calculated by
      fitting several models to the observed signal intensities. When an inversion
      recovery sequence was applied, we were able to measure T1 with a high degree of
      precision by taking into account the imperfection of the inversion pulse. With a
      Turbo-fast low angle shot sequence, we were able to obtain T1 in a short time,
      but low signal-to-noise ratio limited the precision. Signal intensity with SE
      sequence was susceptible to variation with the effective flip angle of 90 degrees
      RF pulse and not suited for T1 measurement.

PMID- 7570585
TI  - Partial 6p trisomy with abnormal ABR and hypogenesis of the corpus callosum.
AB  - A case of 4-month-old male infant with the karyotype 46,XY, -21, +der(21),
      t(6;21)(p22; p13) mat is reported. His cranial magnetic resonance imaging (MRI)
      suggested hypoplastic corpus callosum and auditory brain stem response (ABR)
      revealed brain stem dysfunction.

PMID- 7570584
TI  - Establishment of a cell line from an adenocarcinoma of the lung producing
      carcinoembryonic antigen (CEA) and CA19-9.
AB  - An adenocarcinoma cell line was established from pleural effusion of a 67-year
      old woman and designated as TK-SA. The population doubling time of the cells was
      100.4 hr. Chromosomal analysis revealed the TK-SA to have human aneuploid
      chromosomes with a near-triploid mode. Ultrastructurally, the TK-SA was
      compatible with adenocarcinoma. The cell line was highly tumorigenic. 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye assay demonstrated
      resistance of the cell line to Cis-platin (CDDP), Cyclophosphamide (CPM) and
      Tegafur/Uracil (UFT). High carcinoembryonic antigen (CEA) and CA19-9 levels were
      similar in patient's serum and conditioned medium.

PMID- 7570586
TI  - Electromyographic (EMG) study of the elbow flexors during supination and
      pronation of the forearm.
AB  - Activities of the elbow flexors during supination and pronation of the forearm in
      a normal human volunteer were studied by an electromyography (EMG). The volunteer
      performed the movement slowly or quickly holding elbow flexion at various angles
      with or without a load. The biceps brachii showed an increase and a decrease of
      EMG activities during supination and pronation, respectively. The brachialis and
      brachioradialis showed a reduction and an increment of EMG activities accompanied
      by an increase and a decrease of EMG activities in the biceps brachii,
      respectively. These findings seem to indicate that reciprocal contractions among
      the elbow flexors permit the biceps brachii to work for supination without an
      induction of elbow flexion.

PMID- 7570588
TI  - Cerebral local blood flow with a laser-Doppler flowmetry in rat sleep.
AB  - We preliminary examined whether or not laser-Doppler flowmetry was suitable for
      recording cerebral local blood flow (CLBF) continuously during the sleep
      wakefulness cycle in the rat. As a result, this method of flowmetry led to
      succeed in the real-time monitoring of CLBF on the sleep-wakefulness cycle in a
      freely moving rat, except for the period of gross body movements. Moreover, it
      was proved that CLBF in the hippocampus during paradoxical sleep was
      significantly higher than that during slow-wave sleep. CLBF in the prefrontal
      cortex was a little different from that in the hippocampus.

PMID- 7570587
TI  - Antibiotic pasting for foul putrefactive cancers.
AB  - Putrefaction of cancers in infrequent. Nonetheless, it presents a difficult
      clinical problem of foulness. We prepared 5% antibiotic pastes by adding sodium
      polyacrylate to aliquots of antibiotic solutions, and applied them to
      putrefactive lesions in 4 cases of rectal cancer, 2 of breast cancer and 1 of
      tongue cancer. The putrefaction was promptly brought under control in all of
      them, permitting an improved QOL. Concomitant application of anticancer pastes
      was also found remarkably effective. Use of sulperazone may offer a better chance
      of overcoming the beta lactamase barrier in cases of prolonged use.

PMID- 7570590
TI  - Further observations on the fine structure of the development of the interrenal
      tissue of the chick embryo.
AB  - The interrenal tissue of 8-21 day-old White Leghorn chick embryos and of 1 day
      old chicks was studied by means of electron microscope. The interrenal cells in 8
      10 day-old embryo are characterized by the presence of numerous free ribosomes,
      very small amount of endoplasmic reticulum, oval or club-shaped mitochondria with
      lamellar cristae and of a few small lipid droplets. The fine structural signs for
      steroid secretion, such as round or oval mitochondria with tubular cristae and
      smooth endoplasmic reticulum begin to appear in 11-13 day-old embryo, and the
      interrenal cell of the 16 day-old embryo shows typical morphological
      characteristics for the steroid-secreting cell. After 16 days, the cytoorganelles
      of the interrenal cell do not show any qualitative changes. These facts may
      indicate that the interrenal cell of the domestic fowl is functionally
      differentiated around 11 days of incubation at latest. The interrenal tissue of 8
      9 day-old embryos somewhat resembles a tubular gland, though the zonula occludens
      is not present. In addition, the interrenal cell shows an incomplete cell
      polarity, throughout the embryonic days examined. These findings indicate that
      the interrenal cell of the embryonic domestic fowl, which is derived from a
      mesothelium, remains slightly an epithelial nature.

PMID- 7570589
TI  - Activation of ornithine decarboxylase in epithelial cells of rat intestine.
AB  - Intestinal ornithine decarboxylase (ODC) is strongly induced by dietary amino
      acid and protein feeding. However, the consequence of this induction is unknown.
      In this study, we analyzed the relationship between intestinal ODC activity and
      DNA synthesis in villus and crypt cells of rat intestine. Single amino acid diets
      and protein diets stimulated ODC activity in villus cells, but not in crypt
      cells. However a 20% casein diet induced ODC activity and increased the
      putrescine concentration in villus and crypt cells. Administration of alpha
      difluoromethylornithine, a suicide inhibitor of ODC, prevented both an increase
      in putrescine level and DNA synthesis in the crypt cells. Observations suggested
      that the induction of ODC is necessary to initiate DNA synthesis in rat
      intestinal epithelium.

PMID- 7570591
TI  - Characterization of arachidonate 12-lipoxygenase found in the liver of mongrel
      dog and its immunohistochemical localization in neutrophils.
AB  - The cytosol fraction of non-parenchymal cells isolated from the liver of adult
      mongrel dogs converted arachidonic acid to 12S-hydroxy-5,8,10,14-eicosatetraenoic
      acid. The arachidonate 12-lipoxygenase enzyme reacted with linoleic and alpha-
      and gamma-linolenic acids as well as arachidonic acid. The enzyme was
      immunoprecipitable with an antibody against the leukocyte 12-lipoxygenase, but
      not with an antibody against the platelet 12-lipoxygenase. By immunohistochemical
      observation with anti-leukocyte 12-lipoxygenase antiserum, hepatocytes, Kupffer
      cells and sinusoidal endothelial cells were not immunostained, but a large number
      of neutrophils located in sinusoidal cavities were positively stained. The 12
      lipoxygenase activity thus detected may be attributed predominantly to the
      neutrophils appearing in sinusoidal cavities rather than the non-parenchymal
      cells in the liver of mongrel dog upon infection. In agreement with this finding
      there was essentially no neutrophil accumulation in the liver of Beagle dog which
      had no bacterial and parasitic infection.

PMID- 7570592
TI  - Undifferentiated sarcoma of the liver.
AB  - We report a case of undifferentiated (embryonal) sarcoma (USL) of the liver
      arising in a 5-year-old girl. She had abdominal pain and distension after a blow
      to her abdomen. Exploratory laparotomy disclosed a large tumor arising from left
      lobe of the liver, which showed a typical gross and microscopic appearance of
      USL. Immunohistochemically, the tumor cells reacted with antibodies against
      vimentin, cytokeratin, alpha-smooth muscle actin and muscle actin (HHF35). These
      immunohistochemical variety of the tumor cells may indicate unregulated gene
      expression of anaplastic tumor cells rather than divergent differentiation of
      immature cells as in hepatoblastoma.

PMID- 7570593
TI  - Chromosome assignments of genes for human Na(+)-dependent phosphate co
      transporters NaPi-3 and NPT-1.
AB  - Chromosome assignments for the genes encoding human renal high affinity
      Na/phosphate co-transporters NaPi-3 and NPT-1 were derived by analyzing somatic
      cell hybrid DNAs. Polymerase chain reaction (PCR), using primers specific for two
      human Na/Pi co-transporters demonstrated that the genes for NaPi-3 was assigned
      to human chromosome 5 while that for NPT-1 was assigned to human chromosome 6.
      Renal phosphate transporter genes may be candidates for causing hereditary
      hypophosphatemia with hypercalciuria in humans.

PMID- 7570594
TI  - A physiologically based dosimetry description of acrylonitrile and cyanoethylene
      oxide in the rat.
AB  - The cytochrome P450-mediated oxidation of acrylonitrile (ACN) to the mutagen 2
      cyanoethylene oxide (CEO) is thought to be important for the carcinogenic effects
      of ACN in rats, while glutathione (GSH) conjugation of ACN and CEO is regarded as
      detoxication. A physiologically based dosimetry description for ACN and CEO in
      the male F-344 rat has been developed from in vitro data and studies of the iv
      pharmacokinetics of ACN and CEO. The dosimetry description includes tissue
      partition coefficients and in vitro estimates of the rates of reaction of ACN and
      CEO with hemoglobin and blood macromolecules and the reaction of CEO with tissue
      GSH. Metabolic parameters for ACN and CEO were estimated from iv pharmacokinetic
      studies. Rats were given bolus doses of 3.4, 47, 55, or 84 mg ACN/kg via the
      femoral vein and blood samples were collected at selected time points. ACN and
      CEO blood concentrations were determined by gas chromatography. The iv
      pharmacokinetics of CEO were also determined using 0.6 or 5.3 mg CEO/kg. ACN
      elimination from blood was described by saturable P450 epoxidation (Vmax of 6.5
      mg/hr/kg and Km of 1.5 mg/liter) and first-order GSH conjugation (30 hr-1/kg).
      CEO elimination was described by first-order GSH conjugation (750 hr-1/kg).
      Calculation of hepatic clearance values shows first-pass hepatic extractions of
      61 and 90% for ACN and CEO, respectively. The dosimetry description accurately
      simulated the dose-dependent urinary excretion of ACN metabolites derived from
      epoxidation to CEO and from direct GSH conjugation of ACN. The dose-dependent
      formation of hemoglobin adducts from ACN was also well simulated.

PMID- 7570595
TI  - Differential mechanisms of induction of the mitochondrial permeability transition
      by quinones of varying chemical reactivities.
AB  - A nonspecific increase in permeability of the inner mitochondrial membrane is
      implicated in the mechanism of cell killing by a number of structurally diverse
      agents possessing vastly different chemical reactivities. The objective of this
      investigation was to distinguish the mechanisms by which quinones of varying
      redox cycling and arylating reactivities induce this mitochondrial permeability
      transition in vitro. All of the naphthoquinones examined caused a dose-dependent
      release of calcium from hepatic mitochondria. Associated with this was the
      calcium-dependent depolarization of membrane potential and mitochondrial
      swelling. For substituted naphthoquinones, 2-methyl-, 2,3-dimethyl-, and 2,3
      dimethoxy-1, 4-naphthoquinone, induction of the mitochondrial permeability
      transition correlated with the rate of mitochondrial redox cycling and was
      strongly inhibited by cyclosporine A. In contrast, unsubstituted 1,4
      naphthoquinone induced the permeability transition at concentrations where redox
      cycling was minimal. Induction of the permeability transition by 1,4
      benzoquinone, which does not redox cycle, required that the mitochondria be
      preloaded with calcium and was not inhibited by cyclosporine A. With
      benzoquinone, the initiating event was a calcium-independent depolarization of
      mitochondrial membrane potential. In summary, the evidence indicates that redox
      cycling naphthoquinones induce the mitochondrial permeability transition by
      altering the regulation of the cyclosporine A-sensitive pore. In contrast,
      arylating quinones directly depolarize the mitochondrial membrane which,
      depending on the availability of matrix calcium, may be expressed as a
      cyclosporine A-insensitive permeability transition. These results reveal distinct
      mechanisms for inducing the mitochondrial permeability transition in vitro by
      quinones of varying chemical reactivities, which may be manifested as different
      mechanisms of cell killing.

PMID- 7570597
TI  - Evidence that murine preimplantation embryos express aryl hydrocarbon receptor.
AB  - The underlying mechanism of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced
      alterations during development is thought to be mediated by a cytosolic aryl
      hydrocarbon receptor (Ahr). The specific role of Ahr-mediated changes in gene
      expression during embryonic development has not been elucidated. Recently, we
      reported that TCDD directly affects preimplantation embryo development in vitro,
      by accelerating differentiation of the blastocyst. In the work reported here, we
      provide evidence which suggests that Ahr mRNA and protein are present in mouse
      preimplantation embryos. Our results suggest that the embryo transcribes, rather
      than maternally--inherits Ahr mRNA. In addition, culturing embryos in medium with
      an Ahr antisense oligodeoxynucleotide resulted in a significantly lower incidence
      of blastocyst formation as well as mean embryo cell number. Results from this
      work suggest that Ahr may function in embryonic cell differentiation and
      proliferation independent of its known function in mediating TCDD toxicity in
      other systems.

PMID- 7570596
TI  - Interactions of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl
      congeners for producing rainbow trout early life stage mortality.
AB  - Fish-specific toxic equivalency factors (TEFs), which relate the toxic potency of
      polyhalogenated aromatic hydrocarbons (PHAHs) to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) based on the endpoint of early life stage mortality, have been used
      in assessing the risk to fish early life stage survival of complex mixtures of
      PHAHs in feral fish eggs. Use of TEFs assumes that PHAH congeners act additively.
      However, this has not been unequivocally determined. Isobolograms and a probit
      model were used to assess the validity of the additivity assumption by
      determining the significance of interactions between pairs of polychlorinated
      dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners when
      injected into newly fertilized rainbow trout eggs in ratios bracketing those
      found in feral lake trout eggs from the Great Lakes. The majority of congener
      pairs tested acted additively in causing rainbow trout early life stage
      mortality: [1,2,3,7,8- pentachlorodibenzo-p-dioxin (1,2,3,7,8-PCDD)/TCDD];
      [2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD]; (2,3,4,7,8
      PCDF/TCDD), (2,3,7,8-tetrachlorodibenzofuran/2,3,4,7,8-PCDF); [3,3',4,4'
      tetrachlorobiphenyl (PCB 77)/3,3',4,4',5-pentachlorobiphenyl (PCB 126)];
      [2,3,3',4,4'-pentachlorobiphenyl (PCB 105)/TCDD]; (2,2',4,4',5,5'
      hexachlorobiphenyl/TCDD); (PCB 105/PCB 126); and (2,3',4,4',5
      pentachlorobiphenyl/PCB 126). The only pairs showing evidence of a statistically
      significant interaction that deviated from additivity were (TCDD/PCB 77) and
      (TCDD/PCB 126). Taken together, these results suggest that the use of fish
      specific TEFs to determine TCDD equivalents contributed by individual congeners
      in a fish egg sample and then adding these TCDD equivalents to determine the
      total amount contributed by all congeners may not exactly predict the mortality
      risk posed to fish early life stages by the mixture of TCDD-like congeners in the
      eggs. However, the relatively small deviations from additivity in the rainbow
      trout sac fry mortality test (1- to 4-fold) are less than traditional uncertainty
      factors used in noncancer risk assessments (10-fold/factor) and are not
      sufficient to warrant a change away from the additivity assumption in assessing
      the risk to fish early life stage mortality posed by TCDD and related compounds
      in eggs.

PMID- 7570598
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces diverse retinoic acid metabolites in
      multiple tissues of the Sprague-Dawley rat.
AB  - Retinoic acid metabolism was examined in microsomes prepared from four retinoid
      target tissues of male Sprague-Dawley rats removed 3 days after a single exposure
      to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 5 or 80 micrograms/kg, ip).
      Microsomes from all four tissues catalyzed increased rates of retinoic acid
      metabolism, with the degree of induction following the order: liver > lung =
      kidney = testis. The responses were tissue-specific with respect to the
      metabolites affected, the effects of dose, and the substrate used, [3H]retinoic
      acid or [3H]retinoic acid bound with cellular retinoic acid-binding protein. For
      example, neither 4-hydroxy- nor 18-hydroxy-retinoic acid increased in testis; 4
      hydroxy- but not 18-hydroxy-retinoic acid increased in liver; and both 4-hydroxy-
      and 18-hydroxy-retinoic acid increased in kidney and lung. This ability of TCDD
      to affect diverse retinoic acid metabolites in multiple tissues, including those
      from a physiologically relevant substrate, holocellular retinoic-acid binding
      protein, strengthens the possibility that one aspect of TCDD toxicity involves
      altering the metabolism of retinoic acid.

PMID- 7570599
TI  - Effect of oxygen and sodium thiosulfate during combined carbon monoxide and
      cyanide poisoning.
AB  - In a canine model of combined carbon monoxide (CO) and cyanide (CN) poisoning,
      cardiac output (QT) and oxygen consumption (Vo2) decreased but recovered to
      baseline values by 15 min after toxic exposure; elevated blood CN and lactic
      acidosis persisted for at least another 10 min. Given the rapid spontaneous
      recovery after cessation of toxic exposure, we questioned the efficacy of usual
      treatment with oxygen (O2) and sodium thiosulfate (Na2S2O3) for CN poisoning.
      Accordingly, in seven dogs (26 +/- 3 kg, chloralose and urethane anesthesia), we
      sequentially administered CO by closed circuit inhalation (231 +/- 42 ml) and
      potassium CN by intravenous infusion (0.072 mg.kg-1.min-1 for 17 +/- 3 min).
      Fifteen minutes after toxic exposure, O2 breathing began and Na2S2O3 (150 mg/kg)
      was infused. Measurements were repeated 10 and 45 min after treatment. At the end
      of the CN infusion, QT decreased by 43% and Vo2 decreased by 51%, compared to
      baseline values. Both variables recovered to baseline by 15 min after stopping
      toxic exposure. Significant lactic (4.8 +/- 2.9 mM) acidosis (7.14 +/- 0.10)
      persisted for at least another 10 min. Treatment with oxygen and Na2S2O3 did not
      hasten the recovery of this lactic acidosis or decrease blood cyanide levels
      compared to nontreated dogs. However, after treatment, plasma thiocyanate
      significantly increased from 16.3 +/- 12.5 to 94.4 +/- 72.2 microM, as Na2S2O3
      participated in the increased metabolism of cyanide to thiocyanate. We conclude
      that O2 and Na2S2O3 therapy should be continued during combined CO and HCN
      poisoning. Oxygen increases CO elimination and can enhance anti-CN treatment.
      After infusion or inhalation of CN, when most CN has already penetrated the
      intracellular compartment, postexposure sodium thiosulfate increased the
      metabolism of CN.

PMID- 7570601
TI  - In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p
      dioxin: impaired prostate growth and development without inhibited androgen
      production.
AB  - To determine whether in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) exposure decreases male rat accessory sex organ weights during postnatal
      development secondary to decreases in testicular androgen production or changes
      in peripheral androgen metabolism, pregnant Holtzman rats were administered a
      single dose of TCDD (1.0 microgram/kg, po) or vehicle on Gestation Day 15 and
      offspring were exposed via placental and subsequent lactational transfer until
      weaning on Postnatal Day (PND) 21. Between PNDs 21 and 63, circulating androgen
      concentrations and intratesticular androgen content tended to be decreased by in
      utero and lactational TCDD exposure, but in most cases decreases were not
      statistically significant. In vitro human chorionic gonadotropin-stimulated
      testosterone production by decapsulated testes from TCDD-exposed animals was not
      different from control, although 5 alpha-androstane-3 alpha,17 beta-diol
      production was decreased on PNDs 32 and 49 and increased on PND 63. Taken
      together, these results imply that in utero and lactational TCDD exposure can
      cause subtle decreases in testicular androgen production. However, the biological
      relevance of these reductions is equivocal because they do not correlate
      temporally with one another or with decreases in androgen-dependent male
      accessory sex organ weights. Of the male accessory sex organs, ventral prostate
      (VP) and dorsolateral prostate (DLP) were the most severely affected. Between
      PNDs 21 and 63, relative VP and DLP weights were decreased to 65-84% and 57-80%
      of control, respectively, and the magnitude of observed decreases was greatest at
      early times. In contrast, relative weights of the seminal vesicle and coagulating
      gland ranged from 80 to 104% of control, and the magnitude of observed decreases
      was greatest at later times. The sensitivity of the prostate to TCDD could not be
      explained by tissue-specific decreases in dihydrotestosterone (DHT)
      concentrations. Although VP DHT concentration was decreased to 63% of control on
      PND 21, DHT concentration was not decreased in the VP between PNDs 32 and 63 or
      in the DLP at any time. We conclude that in utero and lactational TCDD exposure
      selectively impairs rat prostate growth and development without inhibiting
      testicular androgen production or consistently decreasing prostate DHT
      concentration.

PMID- 7570602
TI  - Bronchiolarized metaplasia and interstitial fibrosis in rat lungs chronically
      exposed to high ambient levels of ozone.
AB  - The cellular and tissue changes in the lungs of rats were studied using electron
      microscopy following 20 months exposure to a range of ozone levels from 0.12 to
      1.0 ppm. Male and female Fischer 344 rats were exposed and morphometric methods
      were used to determine the volume, surface area, and cellular changes observed in
      bronchiole-alveolar duct regions following chronic ozone exposure. No major
      gender-related effects were observed in response to chronic inhalation of ozone
      nor were significant effects of ozone exposure found in either terminal
      bronchioles or the proximal alveolar regions in animals chronically exposed to
      0.12 ppm ozone. The proximal alveolar regions of animals exposed for 20 months to
      0.5 and 1.0 ppm ozone were significantly altered with exposure. The high-dose,
      long-term exposure to ozone resulted in a pronounced increase in volume of both
      the interstitium and epithelium in the proximal alveolar regions. The thickening
      of the epithelium was due to a change in tissue type from the normal squamous
      epithelium to a cuboidal epithelium similar, but not identical, to that found in
      terminal bronchioles. This bronchiolar epithelial metaplasia of proximal alveolar
      ducts, which was dose related, was composed of differentiated ciliated and Clara
      cells similar to those found in terminal bronchioles. In addition, unique cells
      which contained morphologic features of many different cell types were observed.
      These cells, which may represent stem cells or differentiated but transformed
      cells, were found associated with the bronchiolar metaplasia of alveolar ducts.
      In conjunction with the epithelial changes, cellular and matrix components in the
      interstitium were increased with chronic exposure to 0.5 and 1.0 ppm ozone. All
      matrix components were increased including collagen, elastin, and basement
      membrane, as well as other acellular spaces which did not contain identifiable
      structures. The total volume of interstitial fibroblasts was also increased in
      the high-dose exposure group. Alveolar macrophages were increased only in the 1.0
      ppm exposed animals. The cell and tissue changes in the terminal bronchioles were
      less pronounced indicating a relative resistance of this tissue to ozone and
      mainly consisted of a change in cell type from ciliated to Clara cells in the 1.0
      ppm exposed animals. The relative resistance of bronchiolar tissue to high
      concentration ozone exposure and the extensive bronchiolar epithelial metaplasia
      may be an adaptive mechanism following chronic ozone exposure.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7570600
TI  - Effect of erythropoiesis on splenic cadmium-metallothionein level following an
      injection of CdCl2 in mice.
AB  - The effects of erythropoiesis on cadmium-metallothionein (Cd-MT)2 levels in
      spleen, a major erythropoietic tissue, was examined following sc injection of
      109CdCl2 into mice. As the concentration of Cd in plasma decreased following
      injection of 109CdCl2 into control mice, the levels in spleen and liver increased
      rapidly. After 48 hr, when the concentration of Cd in the erythrocyte (RBC) was
      at maximum, the level of Cd in the spleen, but not liver, had decreased. These
      variations of Cd concentration in spleen and RBC were more notable in mice made
      anemic by phenylhydrazine (PH). Zinc (Zn)-MT was detected in the PH-induced
      hemopoietic spleen. A subsequent injection of CdCl2 further induced Cd-MT in the
      spleen. The protein in spleen contained Cd and Zn but not Cu as in RBCs. Maximum
      levels of Cd-MT in spleen and RBCs of the PH-treated mice were about four times
      higher than those of control mice. The concentration of Cd-MT in the spleen of
      polyemia mice, induced by RBC transfusion, was 50% lower than that of control
      mice. When erythropoietin was injected into the polyemia mice prior to CdCl2, the
      concentration of Cd-MT in spleen increased about sixfold. These changes in Cd-MT
      levels in spleen were not observed in either liver or kidney. The effects of
      erythropoiesis on the concentration of Cd-MT in the spleen corresponded with
      effects seen in RBC. These results suggest that splenic Cd-MT can be the source
      of Cd-MT in mature RBC.

PMID- 7570603
TI  - Microcystin uptake and inhibition of protein phosphatases: effects of
      chemoprotectants and self-inhibition in relation to known hepatic transporters.
AB  - The microcystins (Mcyst) are cyclic peptide hepatotoxins produced by
      cyanobacteria. They are chemically very stable and represent a public health
      threat when they occur in water bodies used for human consumption. Mice injected
      ip with Mcyst (LD50 50-100 micrograms/kg) accumulate Mcyst in the liver and die
      within 2-4 hr with massive intrahepatic hemorrhage. Pretreatment of mice with
      cyclosporin A (CP), rifamycin (Rif), trypan blue (TB), and trypan red (TR)
      protected the animals from a lethal dose of the toxin. The studies reported here
      using the freshly isolated rat hepatocyte model were undertaken in order (1) to
      evaluate the contribution of Mcyst transport in hepatocytes to the mechanism of
      chemoprotection for Mcyst in vivo toxicity by CP, Rif, TB, and TR and (2) to
      better characterize the hepatic Mcyst transporter in this model and determine its
      relationship to other bile acid/organic anion transporters that have already been
      fully described. Incubations with 125I-Mcyst were used to measure Mcyst uptake
      and accumulation in hepatocytes. It has been shown that at the cellular level
      Mcyst binds to and inhibits protein phosphatases 1 and 2A (PP) at nanomolar
      concentrations. Lethal doses of Mcyst in mice resulted in rapid profound
      inhibition of hepatic PP activity. PP activity was also inhibited in hepatocytes
      incubated with 100-500 nM Mcyst. PP inhibition in these studies was used as a
      marker of metabolic effects of the toxin. The chemoprotectants CP (5 microM), Rif
      (50 microM), TR (20 microM), and TB (20 microM) decreased accumulation of Mcyst
      (320 nM, a toxic concentration) after 30 min incubation to 37, 26, 30, and 66%,
      respectively, of that of cells treated with Mcyst only. Inhibition of PP activity
      in these cells was decreased. Inhibition of PP activity in hepatocytes was also
      decreased by known inhibitors of Mcyst transport: 50 microM of the bile acids
      cholate and taurocholate (TC) and 50 microM sulfobromophthalein. For all
      compounds tested the amount of Mcyst accumulated in the hepatocytes correlated
      qualitatively with the extent of PP inhibition. From these results it can be
      concluded that inhibition of Mcyst uptake by hepatocytes is the most likely
      mechanism of chemoprotection for Mcyst in vivo toxicity for TR, TB, CP, and Rif.
      Uptake of Mcyst was unaffected by changes in the ionic composition of the uptake
      buffer but was significantly decreased when PP activity of hepatocytes was
      inhibited by preincubation with Mcyst.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7570604
TI  - Demethylation of methyl mercury in different brain sites of Macaca fascicularis
      monkeys during long-term subclinical methyl mercury exposure.
AB  - Total (T-Hg) and inorganic (I-Hg) mercury concentrations were determined in
      specific brain sites (cerebellum, occipital pole, pons, motor strip, frontal
      pole, temporal pole, thalamus, and pituitary) of female Macaca fascicularis
      monkeys exposed to daily peroral doses (50 micrograms Hg/kg body weight) of
      methyl mercury (MeHg) for 6, 12, or 18 months, or to continuous iv infusion of
      HgCl2 (200 micrograms Hg/kg body wt). In normal weight monkeys (2.4-4.1 kg body
      wt), the average concentration of MeHg (calculated as T-Hg minus I-Hg) was about
      the same in all brain sites, except the pituitary--3.0 micrograms Hg/g at 6
      months, 4.2 micrograms/g at 12 months, and 4.3 micrograms Hg/g at 18 months. MeHg
      concentrations in the pituitary were about 50% of those in the other brain sites.
      In a group of monkeys that were kept unexposed for 6 months following 12 months
      of MeHg exposure, T 1/2 for MeHg was about 37 days in all brain sites, with the
      exception of the pituitary, where it was shorter. The concentration of I-Hg
      increased in all brain sites, but especially in the thalamus and pituitary, with
      the time of MeHg exposure. In most brain sites, I-Hg constituted about 9% of T-Hg
      at 6 and 12 months, and 12% of T-Hg at 18 months. In the pituitary, I-Hg
      increased from 20% of T-Hg at 6 months to 46% at 18 months. Elimination T 1/2 for
      I-Hg was extremely long, 230-540 days in most brain sites and considerably longer
      in the thalamus and pituitary. The concentration of I-Hg in the thalamus did not
      decrease during the clearance period (6 months), while I-Hg in the pituitary
      continued to increase in spite of no additional exposure. The MeHg exposed
      monkeys had several times higher I-Hg concentrations in the brain than monkeys
      exposed to HgCl2, indicating that I-Hg was formed by demethylation of MeHg in the
      brain, and not by brain uptake of I-Hg formed by demethylation elsewhere in the
      body. There were large variations in the relative concentration of I-Hg between
      individual monkeys, but not between brain sites (except thalamus and pituitary).
      Obese monkeys (5.0-6.1 kg body wt) exposed to MeHg had higher concentrations of
      both MeHg and I-Hg than normal weight monkeys in all brain sites, except in the
      pituitary.

PMID- 7570605
TI  - Effects of glutathione depletion on the cytotoxic actions of cadmium in LLC-PK1
      cells.
AB  - Recent studies have shown that exposure of LLC-PK1 cells to micromolar
      concentrations of Cd2+ for 1-4 hr causes the disruption of the junctions between
      the cells, whereas exposure to higher concentrations of Cd2+ for longer periods
      of time causes more severe toxic effects and cell death. Studies suggesting that
      glutathione may serve a protective role against Cd2+ toxicity in other tissues
      and cells led us to examine the effects of glutathione depletion on the cytotoxic
      actions of Cd2+ in the LLC-PK1 cell line. Confluent cells on Falcon cell culture
      inserts were depleted of glutathione by exposing them to 250 microM buthionine
      sulfoximine for 18 hr and then exposed to various concentrations of Cd2+ for up
      to 24 hr. The integrity of cell-cell junctions was assessed by morphologic
      observation of the cells and by monitoring the transepithelial electrical
      resistance. Cell viability was evaluated by monitoring the release of lactate
      dehydrogenase into the medium. The results showed that depleting the cells of
      glutathione did not alter the early junction-perturbing effects of Cd2+, but
      greatly enhanced the lethal effects. In both the glutathione-depleted and the
      normal cells, junctional changes were evident after as little as 1 hr of Cd2+
      exposure. While the normal cells did not begin to die until they had been exposed
      to Cd2+ for 12-24 hr, the glutathione-depleted cells began to die after only 8 hr
      of Cd2+ exposure. Additional results showed that Cd2+ exposure had no effect on
      the total levels of glutathione at the time in which the junctional effects were
      occurring, but caused a marked decrease in glutathione levels at the time the
      cells were dying. These results indicate that the early junctional effects of
      Cd2+ do not result from alterations in intracellular glutathione or sulfhydryl
      metabolism, whereas the more severe cytotoxic effects and cell death may involve
      glutathione-sensitive mechanisms.

PMID- 7570607
TI  - The phytoestrogen beta-sitosterol alters the reproductive endocrine status of
      goldfish.
AB  - There is a growing awareness that chemicals in the environment may function as
      hormone mimics and affect endocrine function in wildlife. In this study, the
      effects of beta-sitosterol, a phytoestrogen present in high concentration in
      bleached kraft pulp mill effluent (BKME), on reproductive fitness of goldfish
      were investigated. Plasma reproductive hormone levels were measured in male and
      female goldfish on Day 4 following two intraperitoneal injections of beta
      sitosterol or an oxidized sitosterol preparation. In some experiments, plasma
      hormone levels were also measured after fish were injected with Ovaprim, which
      contains a superactive analog of salmon GnRH and the dopamine receptor antagonist
      domperidone and leads to increased secretion of gonadotropin (GtH)-II (LH-type
      GtH). Plasma testosterone (T) and 11-ketotestosterone levels in males and T and
      17 beta-estradiol levels in females were significantly decreased in beta
      sitosterol-treated fish on Day 4 and 24 hr after an injection of Ovaprim. Plasma
      GtH-II levels were elevated in male fish treated with beta-sitosterol on Day 4
      and further increased in response to Ovaprim, suggesting that reduced plasma
      steroid levels were not due to effects on pituitary function. In other studies,
      testes pieces from beta-sitosterol-treated goldfish produced reduced levels of T
      and pregnenolone in vitro both basally and in response to the GtH-II agonist
      human chorionic gonadotropin (hCG) when compared to the testes from control fish.
      Basal and hCG-stimulated pregnenolone and hCG-stimulated T were reduced in
      follicles from beta-sitosterol-treated fish; however, basal T production was not
      different from controls. These results suggest that beta-sitosterol reduces the
      gonadal steroid biosynthetic capacity through effects on cholesterol availability
      or the activity of the side chain cleavage enzyme P450SCC. These findings raise
      the possibility that beta-sitosterol could be a contributing factor to the
      reproductive dysfunction observed in fish exposed to BKME.

PMID- 7570606
TI  - Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the human thymus after
      implantation in SCID mice.
AB  - There are conflicting data with regard to the sensitivity of the human immune
      system to the toxic action of the highly toxic environmental pollutant 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). SCID mice engrafted with human fetal thymus
      and liver tissue fragments (SCID-hu mice), which sustain normal human T cell
      differentiation in the thymus graft, were used to directly assess the sensitivity
      of the human thymus for TCDD. Wistar rats and SCID-hu mice were exposed to 1, 5
      or 25 micrograms TCDD/kg body weight. Histopathologic effects were evaluated for
      rat thymus and transplanted human thymus on Day 4 after exposure. The relative
      size of the cortex showed a dose-dependent decrease in both the normal rat thymus
      and grafted human thymus (significant at 25 micrograms/kg). SCID-ra mice (SCID
      mice with a fetal rat thymus and liver graft) were used as an intermediate model
      between the normal rat and SCID-hu mice, and were exposed to the same dose levels
      of TCDD. However, 90% of the SCID-ra mice developed a cutaneous graft-versus-host
      reaction, associated with lymphodepletion of the rat thymus grafts, and hence a
      limited number of SCID-ra mice were available for evaluation of TCDD effects. The
      data obtained in SCID-ra mice were in line with those in normal rat and grafted
      human thymus. In gas chromatography/mass spectrometry analysis, TCDD tissue
      concentrations in the normal rat thymus and grafted human thymus were similar. We
      conclude that the human thymus serves as a target for TCDD, and that the human
      thymus and the Wistar rat thymus display a comparable sensitivity to the toxic
      action of TCDD.

PMID- 7570609
TI  - Mercury uptake by primary cultures of rat renal cortical epithelial cells. II.
      Effects of pH, halide ions, and alkali metal ions.
AB  - The effects of pH, halide ions, and alkali metal ions on the uptake of inorganic
      mercury (Hg) were investigated in confluent primary cultures of rat renal
      cortical epithelial cells. The cells were incubated with 1 microM Hg in phosphate
      buffer at pH 5.5, 6.4, or 7.4 for 30 min at 37 degrees C. Incubation of cells at
      pH 5.5 resulted in a 22% increase in total Hg accumulation over those cells that
      were incubated at pH 7.4. Almost all of this increase was accounted for in the
      membrane fraction. In contrast, there was a 33% reduction in internalized Hg in
      cells incubated at pH 5.5. This may be explained by the conversion of hydroxide
      forms of Hg (Hg(OH)Cl and Hg(OH)2) to the chloride forms (HgCl2, HgCl3-, and
      HgCl4(2-) at a lower pH (decreased OH-) condition. In the presence of halide
      ions, the cells internalized Hg in the relative order of affinity of the halide
      ions for Hg2+ (i.e., F- < Cl- < Br- < I-). Br- and I- resulted in a 67 and 142%
      increase in internalized Hg over that by Cl-. The relatively high membrane
      binding and internalization of Hg in the presence of Br- and I- was possibly due
      to the formation of highly lipophilic complexes of Hg (i.e., HgBr2 and HgI2). The
      replacement of NaCl in the incubation medium by KCl caused a 36% decrease in
      internalized Hg. LiCl had a similar effect on the internalization of Hg. The
      above results suggest that in rat renal proximal tubules Hg uptake involves Na(+)
      and H(+)-dependent mechanisms.

PMID- 7570611
TI  - Cytosolic C-S lyase activity in human kidney samples-relevance for the
      nephrotoxicity of halogenated alkenes in man.
AB  - Human renal cortex cytosolic samples were screened for C-S lyase (EC 4.4.1.13)
      activity using cysteine conjugates of halogenated aliphatic and aromatic
      hydrocarbons as substrates. Cystosolic activity was greatest with S-(1,2
      dichlorovinyl)-L-cysteine (DCVC) and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine
      (TFEC) (72.0 +/- 26.8 and 74.4 +/- 38.3 nmol pyruvate formed/mg protein/120 min.
      respectively). Less than five fold inter-individual variation was observed. In
      contrast to the low C-S lyase activity detectable in rat cytosol, no cleavage of
      the aromatic conjugates S-(2-benzothiazolyl)-L-cysteine (BTC), S-(2,3,5,6
      tetrachlorophenyl)-L-cysteine (TCPC) and S-(4-bromophenyl)-L-cysteine (4-BPC) was
      detectable in human cytosol. Structure-activity relationships showed that
      increasing the fluorinated carbon chain length of the halogenated hydrocarbon
      species decreased conjugate cleavage by C-S lyase. The position and number of
      fluorine and chlorine atoms on the parent hydrocarbon determined the extent of
      cysteine conjugate C-S cleavage. Activity increased with an increase in fluorine
      and chlorine substitution and shortening of carbon chain length in the rat,
      although in human cytosol an increase in chlorine substitution resulted in
      decreased activity.

PMID- 7570610
TI  - Physiologically-based pharmacokinetic modeling and bioactivation of xenobiotics.
AB  - This paper describes the development and implementation of physiologically-based
      pharmacokinetic (PB-Pk) models to examine the disposition of xenobiotics and
      their bioactivation. In a PB-Pk model, the structure of the model is based, to as
      great extent as practicable, on the actual physiological and biochemical
      structure of the animal system being described. This paper provides an overview
      of the PB-Pk modeling approach using a series of models as examples. PB-Pk models
      for styrene and the dihalomethanes are discussed in relation to their ability to
      predict the kinetics of uptake, distribution, metabolism (bioactivation), and
      elimination in both rodents and humans. Three models are discussed which
      demonstrate the process of describing increasing complexity in bioactivation with
      reference to saturation of metabolism (methylene chloride), suicide enzyme
      inactivation (trans-1,2-dichloroethylene), and glutathione depletion (allyl
      chloride). Experimental studies to quantify these particular examples of non
      linear kinetics were conducted by closed chamber gas uptake techniques. All of
      these behaviors can be quantitatively expressed within the framework of a PB-Pk
      model.

PMID- 7570608
TI  - Identification of the mouse liver 44-kDa acetaminophen-binding protein as a
      subunit of glutamine synthetase.
AB  - Identification of proteins that covalently bind acetaminophen (APAP) is essential
      for a clearer understanding of the hepatotoxicity that results after an APAP
      overdose. Birge et al. (1991) have reported that in our mouse model system a
      membrane-associated 44-kDa acetaminophen-binding protein is the earliest target
      detected immunochemically following administration of an hepatoxic dose of APAP.
      To identify this 44-kDa protein, liver microsomes from mice administered 600 mg
      APAP/kg were extracted with Triton X-114 and the resulting aqueous fraction was
      adsorbed to DEAE-cellulose. Further purification of the DEAE eluate by reverse
      phase HPLC and by two-dimensional (2D) gel electrophoresis indicated that four
      proteins of approximately 44 kDa with pIs ranging from 6.7-7.0 were targeted by
      APAP. The most highly arylated of these 44-kDa isoforms (pI 7.0) was excised from
      2D gels, digested with trypsin, and the resulting peptides were separated by
      reverse-phase HPLC. The two best resolved peptides were sequenced and 14 of the
      15 amino acids detected were found to be identical to subunits of mouse liver
      glutamine synthetase (EC 6.3.1.2). Purification of glutamine synthetase from APAP
      treated mice confirmed that the enzyme is indeed targeted by APAP in vivo. Since
      the intracellular activity of glutamine synthetase is significantly decreased
      after the administration of APAP to hepatocytes in culture, it is likely that the
      arylation of this enzyme may be involved in the ensuing hepatotoxicity.

PMID- 7570612
TI  - Immunologic and biologic markers for silicone.

PMID- 7570614
TI  - Red blood cell antioxidants in human volunteers exposed to ozone.
AB  - Indices of red blood cell (RBC) antioxidant capacity can undergo changes upon
      exposure to oxidants, either acutely or chronically. To investigate whether these
      changes might provide a biochemical marker for acute environmental ozone
      exposure, we assessed RBC glutathione (GSH) and catalase (CAT) responses in seven
      normal volunteers exposed to 0.16 ppm ozone for 7.5 hours compared to the same
      measurements following sham exposure to clean air. For each subject, an interim
      period of two weeks separated the two exposure studies. Investigators performing
      the RBC assays were unaware of the environmental conditions. No changes in either
      GSH or CAT were observed for any study condition when compared to pre-study
      values. Our conclusion is that RBC antioxidants do not accurately reflect in vivo
      exposure to ozone at concentrations readily attainable during periods of heavy
      urban pollution. Our data dispute the value of these indices as markers of acute
      environmental photochemical oxidant exposure.

PMID- 7570613
TI  - Age-related variations of lipid peroxidation in cadmium-treated rats.
AB  - Under specific conditions, Cd can induce a prooxidant state in biological systems
      resulting in the peroxidation of the polyunsaturated fatty acids. We investigated
      in vivo this phenomenon in major target organs of Long Evans rats (12- and 36
      week-old), 24 hours after being injected i.p. with a range of cadmium chloride
      doses (0.00, 0.05, 0.25, 1.0 or 2.5 mg Cd/kg). The measurements of the
      thiobarbituric acid reactive substances demonstrated that the lungs showed the
      highest Cd-induced LPO in the 12-week-old rats even if the liver and kidneys
      accumulated the greatest amounts of Cd. Cd-induced LPO as measured by TBARS assay
      in the 36-week-old groups was, in all organs, less pronounced even if the control
      levels were higher for these groups. The reasons for this age-dependent
      differences are not clear. Some components of the antioxidant defense system were
      differently modulated as a function of age. However, it is not certain whether
      these changes have a causative role in the induction of LPO following Cd
      exposure.

PMID- 7570616
TI  - Age-dependent neurotoxicity in rats chronically exposed to low level lead
      ingestion: phospholipid metabolism in synaptosomes and microvessels.
AB  - The uptake of [3H]Ch and [3H]MI by synaptosomes or microvessels, the
      concentration of membrane phospholipids, and the incorporation of [3H]Ch or
      [3H]MI into the respective phospholipids in synaptosomes or microvessels, were
      studied in samples obtained from the brain of control rats and rats exposed to a
      low-level lead ingestion starting prenatally, neonatally or at an adult age. The
      Vmax values for the uptake of [3H]Ch by control-neonatal and control-adult
      samples were significantly different. However, there was no significant
      difference in the Vmax values for the uptake of [3H]MI by control-neonatal and
      control-adult samples. The same was true for the Km values for the uptake of
      [3H]Ch or [3H]MI. Chronic exposure of embryonic and neonatal rats to a low-level
      lead ingestion inhibited the rate of uptake of [3H]Ch and [3H]Mi by the brain
      synaptosomes or microvessels, reduced the concentrations of Ch and MI
      phospholipids in membranes of these tissues, and did not effect the incorporation
      of [3H]Ch and [3H]MI into the respective membrane phospholipids. In adult rats,
      these changes were not observed following chronic exposure. These observations
      suggest that Ch and MI transport mechanisms in the brain of embryonic and
      neonatal rats are sensitive to chronic low-level lead ingestion but Ch and MI
      transport mechanisms in the brain of adult rats are not. A lead-induced decrease
      in the availability of Ch and MI in the brain may be responsible for the observed
      decrease in the concentrations of phospholipids.

PMID- 7570617
TI  - Multiple chemical sensitivities--fact or myth.

PMID- 7570615
TI  - A case study in avoiding a deadly legacy in developing countries.

PMID- 7570620
TI  - A weight-of-evidence approach for assessing interactions in chemical mixtures.
AB  - The risk assessment process must encompass all available toxicological data and
      scientific evidence on the plausible toxicities of a chemical or chemical
      mixture. As an extension to the approaches used to conduct risk assessments on
      chemical mixtures, a preliminary scheme, analogous to the IARC classification of
      carcinogens, is proposed to express the weight of evidence for the interactions
      in binary mixtures. This scheme is based on composite representation of all the
      toxicological evidence from animal bioassays and human data, pharmacokinetics
      studies, metabolism studies, and structure activity relationships. In addition,
      factors such as the relevance of route, duration and sequence of exposure,
      toxicological significance of interactions and the quality of in vivo and in
      vitro data are taken into consideration. The scheme yields an alphanumeric
      classification that can be used for qualitative risk assessment, and has the
      potential, as demonstrated in this paper, for quantitative application to site
      specific risk assessments. Furthermore, the scheme can be used to estimate
      interactions or form hypotheses concerning binary interactions. It is flexible
      and allows all pertinent information to be incorporated in a methodical and
      consistent manner. Research is needed to identify interaction patterns for
      simultaneous and sequential exposure scenarios of chemical pollutants in order
      that this scheme may be developed further and its usefulness and limitations may
      be tested.

PMID- 7570621
TI  - Detection of protein changes in serum of workers following inhalation exposure to
      toluene diisocyanate vapors.
AB  - Serum samples of 10 workers undergoing occupational type inhalative challenge
      tests by toluene diisocyanate (TDI) were investigated by anion-exchange fast
      protein-liquid-chromatography (FPLC) and polyacrylamide-gel electrophoresis (PAGE
      SDS). Their serum chromatography profiles were compared to those of 20 unexposed
      individuals. The peak height of the first prealbumin peak in sera of workers
      after inhalative challenge tests was significantly different (p > 0, 01 Chi
      square test) compared to that obtained before exposure and to that of unexposed
      subjects. In addition, qualitative changes of these peaks were also noted in sera
      of workers exposed to TDI. In the cases of exposed individuals, that peak was
      more diffuse with some shoulders and less symmetric in appearance. Similarly,
      PAGE-SDS of the serum proteins, followed by silver nitrate staining, revealed a
      different banding pattern after in vivo TDI exposure. One of the serum components
      at approximately 15 kDa showed an increase of staining intensity after exposure
      (n = 10), compared to unexposed subjects or to patients before exposure. This
      serum fraction has not yet been identified. The results here demonstrate that it
      is possible to detect changes of serum proteins in TDI-exposed individuals within
      a relatively short analysis time. This could be useful for biological monitoring
      of exposure, since no method for such is yet available.

PMID- 7570619
TI  - Mutagenic activity of p-toluenesulfonhydrazide.
AB  - Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there
      is relatively little toxicological data. In this study, the mutagenic activity of
      TSH was determined in the Salmonella/mammalian microsome assay and the in vitro
      chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene
      mutations both with and without metabolic activation in the Salmonella/mammalian
      microsome assay but that it did not induce chromosomal aberrations in Chinese
      hamster ovary cells. The results of this study indicate that TSH is an in vitro
      mutagen and should be assessed for in vivo mutagenicity.

PMID- 7570618
TI  - Subchronic toxicity study of dicyclopentadiene vapor in rats.
AB  - Fischer 344 rats were exposed by inhalation to 0, 1, 5 or 50 ppm
      dicyclopentadiene (DCPD) vapor 6 hr/day, 5 days/week for 13 weeks, followed by a
      13-week recovery period. Animals were euthanized following completion of exposure
      at 2, 6, or 13 weeks and at postexposure weeks 4 or 13. No mortality, overt
      signs, body weight changes, hematologic or clinical chemistry values were related
      to DCPD exposure. In the high-exposure male rats, relative liver weights were
      significantly increased but with no accompanying histopathologic changes.
      Exposure to DCPD produced adverse kidney effects in male, but not female, rats as
      evidenced by the excretion of epithelial cells in the urine. Histologic changes
      were localized to the proximal tubules of the kidney and included increased
      accumulation of protein droplets, regenerative epithelium, and the presence of
      intraluminal proteinaceous material. In addition, several alterations in renal
      function were observed. Urinary Na+ excretion rates were decreased and urinary K+
      excretion rates were increased throughout the exposure period; however, glucose
      was not present in the urine, and creatinine clearance was normal. The ability of
      the kidney to concentrate urine was also impaired. After the recovery period,
      many of the treatment-related kidney effects were not observed, including the
      presence of hyaline droplets in the proximal tubules and epithelial cells in the
      urine. These findings indicate an overall low degree of systemic toxicity
      following subchronic inhalation exposure of dicyclopentadiene at exposure levels
      up to 50 ppm. The only effect that was observed was a male rat-specific
      nephropathy that is characteristic of the hyaline droplet nephropathy produced by
      a diverse group of compounds.

PMID- 7570624
TI  - Proceedings of the 4th International Symposium on Neurotoxins in Neurobiology.
      Bath, United Kingdom, 19-23 September 1993.

PMID- 7570622
TI  - Immune functional impairment in patients with clinical abnormalities and silicone
      breast implants.
AB  - Silicone, previously thought to be a biologically inert and harmless material,
      has now been reported to elicit antibody response and to be responsible for
      adjuvant disease in humans. The present study was designed to evaluate the immune
      function of forty individuals who had undergone silicone breast augmentation for
      a period of longer than ten years and who were compared with 40 sex and age
      matched controls. The following immunological functions were studied: lymphocyte
      subset analysis, lymphocyte mitogenic response, NK cytotoxic activity and markers
      for autoimmunity such as ANA, rheumatoid factor immune complexes such as smooth
      muscle, myelin, and thyroid, and tissue antibodies. Results of lymphocyte
      subpopulation analysis showed significantly elevated T helper/suppressor ratio in
      60% and significantly decreased T helper/suppressor ratio in 7.5% of the silicone
      implant group, while the control group showed increased helper/suppressor ratio
      only in 10% of tested individuals and no significant decrease in the T
      helper/suppressor ratio. There was 20% inhibition in T cell mitogenic responses
      in the silicone implant group, which is significant when compared to the
      controls. When NK cytotoxic activity was compared between the two groups,
      significant inhibition in the ability of lymphocytes to kill tumor target cells
      was observed in the silicone implant group. This inability of target cell lysis
      was attributed to the demonstrated lack of granularity of NK cells from the
      silicone implant group. There was significant increase in: immune complexes, anti
      nuclear antibodies, anti-thyroid antibodies, anti-striated muscle cell antibody,
      and anti-myelin basic protein antibodies. These immunological abnormalities in
      individuals who underwent silicone breast augmentation indicate a mechanism of
      tissue injury to these patients, causing autoimmune diseases or syndromes. Since
      autoimmunity in some other conditions is associated with abnormalities in the HLA
      serotyping system, and since some collagen vascular diseases have been associated
      with a higher incidence of the HLA serotyping system, it is recommended that HLA
      studies be included in future investigations of immune-mediated abnormalities
      associated with silicone breast augmentation. Our findings here show definite
      abnormalities of the T helper/suppressor ratio, increased autoimmunity, as well
      as increased production of immune complexes. Silicone implants have been used in
      cosmetic and reconstructive surgery more than 30 years (Brown et al., 1960). The
      gel used in the implant is produced from silicone, which is then related with
      methyl chloride and polymerized to form stable polydimethylsiloxane (Brown, et
      al., 1960). There have been a number of reports describing the occurrence of
      connective tissue disease in patients after the implantation of
      silicone.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7570623
TI  - Toxicological investigations in the semiconductor industry: II. Studies on the
      subacute inhalation toxicity and genotoxicity of gaseous waste products from the
      aluminum plasma etching process.
AB  - Male and female Wistar rats were exposed to waste gas arising from a plasma
      etching process in the semiconductor industries for six hr per day, five days per
      week, for four weeks in order to characterize subacute organ toxicity and
      genotoxicity. The waste gas was a complex mixture of different chlorinated
      hydrocarbons, inorganic by-products, and unused process gases, diluted by room
      air. Neither death nor behavioral changes occurred after subacute exposure. No
      significant exposure-related effects on body weight gain, hematology, or
      cardiovascular parameters were observed. Only slight effects on organ weights and
      clinical chemistry were seen in the exposed animals. The exposed rats of both
      sexes showed statistically significant increases in chromosomal aberrations and
      sister chromatid exchanges in bone marrow cells.

PMID- 7570625
TI  - Muscarinic toxins from the venom of Dendroaspis snakes with agonist-like actions.
AB  - The venom of some Dendroaspis snakes contains small proteins (7500 mol. wt) that
      inhibit the binding of radiolabelled muscarinic antagonist to brain synaptomal
      membranes. There were no peptides described among muscarinic ligands until Adem
      et al. (Biochim. biophys. Acta 968, 340-345, 1988) reported that muscarinic
      toxins (MTxs), MTx1 and 2 were able to inhibit 3H-QNB binding to rat brain
      membranes. Since MTxs inhibit around half of specific binding of 3H-quinuclidinyl
      benzilate (3H-QNB) and 3H-N-methyl-scopolamine (3H-NMS), which do not
      discriminate between subtypes of muscarinic receptors, it has been proposed that
      MTxs might selectively bind to some subtype. MTx1 and 2 from Dendroaspis
      angusticeps almost completely inhibit the binding of 3H-pirenzepine (3H-PZ), a
      preferential M1 muscarinic receptor subtype ligand to cerebral cortex
      synaptosomal membranes. A much higher concentration was needed to inhibit
      partially 3H-PZ binding to atrial muscarinic receptors. These results support the
      hypothesis that MTx1 and 2 may be M1 selective muscarinic ligands. Similar
      activities have been found in Dendroaspis polylepis and D. viridis venoms, but
      with lower affinities. The Ki obtained from inhibition curves of the binding of
      3H-PZ showed that MTx1 has higher affinity for the putative M1 muscarinic
      receptor subtype, followed by MTx2. DpMTx has lower affinity, while DvMTx seems
      to have the lowest affinity. All these peptides are devoid of anticholinesterase
      activity. Dendrotoxin and fasciculin from D. angusticeps venom do not inhibit the
      binding of muscarinic radioligands to cerebral cortex membranes. The injection of
      MTxs into dorsal hippocampus of rats immediately after training in an inhibitory
      avoidance task improves memory consolidation, as does oxotremorine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7570626
TI  - A snake toxin against muscarinic acetylcholine receptors: amino acid sequence,
      subtype specificity and effect on guinea-pig ileum.
AB  - The sequence of muscarinic toxin 1 (MT1) from Dendroaspis angusticeps (green
      mamba) was determined (66 amino acids, M(r) 7509). The central part, peptide 25
      40, is rich in hydrophobic amino acids, which is a characteristic of muscarinic
      toxins. MT1 started to inhibit [3H]-NMS (N-methylscopolamine) binding to
      synaptosomal membranes of porcine brain (contains all five receptor subtypes) at
      about 1 nM and to membranes from pig heart muscle (only subtype m2) at about 1
      microM. Binding of [3H]-AF-DX 384 to heart was inhibited with an IC50 of 14
      microM and to brain in two steps. In the first step (IC50 = 32 nM) binding
      decreased by 37%, indicating that the toxin acted on m1 or m4 receptors, each
      accounting for about 40% of total receptor content. The second step was similar
      to the effect on heart. Pirenzepine inhibited binding of [125I]-MT1 to brain
      receptors with an IC50 of 6.5 nM, corresponding to a Ki of about 6 nM. Literature
      values of Ki for pirenzepine are 16-18 nM for m1 and > or = 120 mM for other
      subtypes. This indicates binding to m1 receptors. mM for other subtypes. This
      indicates binding to m1 receptors. [125I]-MT1 bound to brain with a Kd of 20 nM
      and a Hill coefficient of 1.0, i.e. one toxin molecule per receptor. In guinea
      pig ileum, MT1 (670 nM) produced a rapid contraction, reversible by atropine. The
      toxin may be an agonist, but might also cause contraction by inducing
      acetylcholine release by a different mechanism.

PMID- 7570627
TI  - Actions of neurotoxins (bungarotoxins, neosurugatoxin and lophotoxins) on insect
      and nematode nicotinic acetylcholine receptors.
AB  - Neurotoxins of natural origin have proved to be of considerable value in the
      isolation and characterization of vertebrate muscle and neuronal nicotinic
      acetylcholine receptors (nAChRs). To date, they have been used less extensively
      in studies of invertebrate nAChRs. Here we examine how a variety of neurotoxins
      (the snake toxins alpha-bungarotoxin, alpha-BGT, and kappa-bungarotoxin, kappa
      BGT, the molluscan toxin, neosurugatoxin, and the soft coral toxins, lophotoxin
      and bipinnatin-B) can be used to characterize nAChRs in an insect, Periplaneta
      americana, and in a parasitic nematode, Ascaris suum. The agonist profiles of
      these nAChRs are distinct, but the most striking differences are in the actions
      of antagonists. Whereas the insect nAChR is blocked by both alpha- and kappa
      bungarotoxins, the nematode receptor is only blocked by kappa-BGT. Neosurugatoxin
      blocks nAChRs in both species, but the lophotoxins which block all nAChRs
      investigated to date are much less effective on the Ascaris muscle receptor.

PMID- 7570628
TI  - Structure-activity studies on scorpion toxins that block potassium channels.
AB  - Scorpion venoms contain toxins that block different types of potassium channels.
      Some of these toxins have affinity for high conductance Ca(2+)-activated K+
      channels and for dendrotoxin-sensitive voltage-dependent K+ channels. The
      structural features that determine the specificity of binding to different
      channel types are not known. We investigated this using natural and synthetic
      scorpion toxins. We have tested the effects of charybdotoxin (CTX) and two
      homologues (Lqh 15-1 and Lqh 18-2), iberiotoxin (IbTX), and kaliotoxin (KTX) from
      the scorpions Leiurus quinquestriatus hebreus, Buthus tamulus and Androctonus
      mauretanicus mauretanicus, respectively, and synthetic variants of CTX, namely
      CTX2-37, CTX3-37, CTX4-37, and CTX7-37, on a Ca(2+)-activated K+ current (IK-Ca)
      at a mammalian motor nerve terminal, and on the binding of a radiolabelled
      dendrotoxin, 125I-DpI, to voltage-dependent K+ channels on rat brain synaptosomal
      membranes. The native toxins contain 37-38 amino acid residues, they are over 30%
      identical in sequence (CTX and IbTX are 68% identical), and they have similar
      three-dimensional conformations. All toxins, except IbTX, displaced 125I-DpI from
      its synaptosomal binding sites: Lqh 18-2 (Ki = 0.25 nM), KTX (Ki = 2.1 nM), CTX
      (Ki = 3.8 nM), CTX2-37, (Ki = 30 nM), Lqg 15-1 (Ki = 50 nM), CTX3-37 (Ki = 60
      nM), CTX4-37 (Ki = 50 nM), CTX7-37 (Ki = 105 nM). IbTX had no effect at 3 microM.
      When variants of CTX with deletions at the N-terminal portion were tested for
      their activity on IK-Ca on motor nerve terminals in mouse triangularis sterni
      nerve-muscle preparations, CTX3-37 and CTX4-37 were ineffective at 100 nM; and
      CTX7-37 was ineffective at up to 1 microM. IbTX and CTX (100 nM) completely
      blocked IK-Ca, but KTX (100 nM) did not affect the nerve terminal IK-Ca.
      Different residues appear to be important for interactions of the toxins with
      different K+ channels. IbTX did not displace dendrotoxin binding, but it did
      block IK-Ca, whereas KTX was as active as CTX against dendrotoxin binding but it
      did not affect the IK-Ca of the motor nerve terminals. The N-terminal section of
      the toxins appears to be particularly involved in block of IK-Ca at the motor
      nerve terminal: it is truncated in the inactive synthetic CTX variants; and it is
      positively charged at lysine-6 in KTX (which is inactive), but negatively charged
      in IbTX and neutral in CTX.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7570629
TI  - Ammodytoxin A acceptor in bovine brain synaptic membranes.
AB  - Ammodytoxin A, the presynaptic neurotoxin from Vipera ammodytes ammodytes venom,
      was found to bind specifically and with high affinity to bovine cortex synaptic
      membrane preparation. The detected ammodytoxin A high-affinity binding was
      characterized by equilibrium binding analysis which revealed a single high
      affinity binding site with Kd 4.13 nM and Bmax 6.67 pmoles/mg of membrane
      protein. 125I-ammodytoxin A was covalently cross-linked to its neuronal acceptor
      using a chemical cross-linking technique. As revealed by subsequent SDS-PAGE
      analysis and autoradiography, 125I-ammodytoxin A specifically attached to
      membrane components with apparent mol. wts 53,000-56,000. Besides by the native
      ammodytoxin A, the binding of radioiodinated ammodytoxin A to the neuronal
      acceptor was highly attenuated, also by other two iso-neurotoxins from V. a.
      ammodytes venom, ammodytoxins B and C, and neurotoxin crotoxin B from the venom
      of the South American rattlesnake (Crotalus durissus terrificus). Vipera berus
      berus phospholipase A2 was a weaker inhibitor, whereas nontoxic phospholipase A2,
      ammodytoxin I2 and myotoxic phospholipase A2 homologue, ammodytin L, both from V.
      a. ammodytes venom as well, were very weak inhibitors. No inhibitory effect on
      125I-ammodytoxin A specific binding at all was, however, obtained with alpha
      dendrotoxin, beta-bungarotoxin and crotoxin A, respectively. Treatment of
      synaptic membranes with proteinase K and Staphylococcus aureus V-8 proteinase, a
      combination of PNGase F and neuroaminidase, heat or acid lowered the 125I
      ammodytoxin A specific binding to various extents but never completely abolished
      it. The ammodytoxin A binding site in bovine synaptic membranes is thus most
      likely a combination of membrane glycoprotein acceptor and membrane
      phospholipids. As ammodytoxin A reduced the second negative component of the
      perineural waveform, measured on mouse triangularis sterni preparation, which is
      very likely a result of an inhibition of a fraction of the terminal K+ currents,
      the ammodytoxin A acceptor could well be connected with K+ channels.

PMID- 7570630
TI  - Binding proteins on synaptic membranes for crotoxin and taipoxin, two
      phospholipases A2 with neurotoxicity.
AB  - Crotoxin and taipoxin are both neurotoxic phospholipases A2 capable of affecting
      the presynaptic activity to bring about ultimate blockade of synaptic
      transmission. The enzymatic activity has generally been considered to be
      necessary but not sufficient for the blockade. Since many phospholipases A2 with
      comparable or even higher enzymatic activity are not toxic, it has been
      postulated that the difference lies in the affinity of binding to the presynaptic
      membrane. In confirmation of this proposition, we and others have previously
      shown that iodinated crotoxin and taipoxin bind specifically with high affinity
      to the isolated synaptic membrane fraction from guinea-pig brain, whereas
      specific binding is not detected with the nontoxic pancreatic phospholipase A2.
      Experiments based on photoaffinity labeling and simple chemical cross-linking
      techniques have led to the identification of three polypeptides preferentially
      present in neuronal membranes as (subunits of) the binding protein(s) for
      crotoxin and/or taipoxin. Some, but not all, other toxic phospholipases A2 also
      appear to be ligands for the three polypeptides. We now report studies on partial
      purification of these polypeptides using affinity chromatography and other
      techniques. In order to learn the normal physiological roles played by the toxin
      binding proteins, the phospholipase-independent effects of the toxins on the
      synaptosomes have been sought. We have found that under Ca(2+)-free condition,
      taipoxin or crotoxin inhibits with IC50 of 20-1000 nM the Na(+)-dependent uptake
      of norepinephrine, dopamine and serotonin by the synaptosomes. In contrast,
      choline uptake is not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570632
TI  - Immunogenicity of a disulphide-containing neurotoxin: presentation to T-cells
      requires a reduction step.
AB  - It is known that production in a host of antibodies against a protein is
      associated with various molecular events. These include the stimulation of
      specific T-lymphocytes, a step that implies the processing of the protein into
      peptides by various endosomal/lysosomal enzymes, such as cathepsins. Strikingly,
      however, we observed in vitro that cathepsins B and D have no degrading effect on
      toxin alpha from Naja nigricollis, a curaremimetic toxin of 61 amino acids and
      four disulphides. In sharp contrast, the enzymes exert an efficient cleavage of
      the toxin polypeptide chain once the toxin disulphides are reduced. We also found
      that the fully reduced toxin and the native toxin were presented with comparable
      efficiency to two different T-hybridomas by antigen-presenting cells (APC).
      Together, the data suggest that presentation of toxin fragments to T-cells
      requires a reduction step of toxin disulphides and, in agreement with previous
      findings, that this step may be achieved by APC. We wish to suggest that this
      phenomenon may commonly occur for any toxic proteins that contain disulphides.

PMID- 7570631
TI  - Cloning and expression of mamba toxins.
AB  - Mamba venoms contain pharmacologically active proteins that interfere with
      neuromuscular transmission by binding to and altering the normal functioning of
      neuronal proteins involved, directly or indirectly, with regulating nerve
      transmission. Of the mamba toxins studied to date, many act on voltage-sensitive
      K+ channels, nicotinic or muscarinic acetylcholine receptors, or
      acetylcholinesterase. In an attempt to clone, characterize, and express the genes
      encoding these toxins, as well as other genes specifying activities not
      completely elucidated as yet, a cDNA library was constructed from mRNA isolated
      from the glands of the black mamba. Clones from the library harboring sequences
      encoding 14 different mamba toxins were isolated and characterized by nucleotide
      sequence analysis. Genes coding for three proteins, dendrotoxins (DTX) K, I, and
      E, were expressed as maltose-binding (MBP) fusion proteins in the periplasmic
      space of Escherichia coli. The DTXK-MBP fusion protein was affinity purified,
      cleaved from its chaperon, and the recombinant DTXK purified from MBP.
      Recombinant DTXK was shown to be identical to native DTXK in its N-terminal
      sequence, chromatographic behavior, convulsion-inducing activity, and binding to
      voltage-activated K+ channels in bovine synaptic membranes. Computer modeling was
      employed to create three-dimensional structures of DTXK and DTX1 from the X-ray
      crystal structure of alpha-DTX utilizing both structural and sequence homologies.
      Comparisons were made between the three toxins, providing a framework for site
      directed mutagenesis.

PMID- 7570633
TI  - Low molecular weight components from black widow spider venom.
AB  - Highly purified alpha-latrotoxin from the black widow spider venom (alpha-LTX)
      consists of two polypeptides with mol. wts of 130,000 and 8000 (LMWP). We have
      isolated two low mol. wt proteins LMWP and LMWP2 from the low mol. wt fraction of
      this venom. The chemical properties of these proteins and partial amino acid
      sequence of novel protein LMWP2 were studied. By means of i.v. or
      intracerebroventricular injections into mice it was shown that low mol. wt
      components of the venom at concentrations of 2.3 mg/kg and 0.8 mg/kg,
      respectively, did not possess any direct toxic effect on vertebrates. Injections
      of each protein into the third thoracic segment of cockroaches Periplaneta
      americana (doses up to 80 micrograms/g) did not cause lethality or paralysis of
      insects.

PMID- 7570634
TI  - Effect of alkaloid toxins from tropical marine sponges on membrane sodium
      currents.
AB  - Dibromosceptrin and clathrodin are alkaloid compounds purified from tropical
      marine sponges of the genus Agelas. Experiments done using the whole cell
      configuration of the patch clamp technique revealed that these compounds have
      neurotoxic activity. Both compounds decreased by 27-40% the average maximum
      amplitudes of pharmacologically isolated inward sodium currents in cells isolated
      from chick embryo sympathetic ganglia. Current-voltage data, fitted using
      Boltzmann's equation, did not show any effect of these agents on the voltage
      dependence of current activation. However, the voltage dependence of current
      inactivation was shifted toward more negative potentials by dibromosceptrin,
      changing by an average of 20 mV the voltage for 50% inactivation. In contrast,
      clathrodin shifted this voltage dependence of inactivation toward more positive
      potentials and changed the voltage for 50% inactivation by 14 mV. Time for
      current reactivation was not altered by clathrodin but was slightly prolonged by
      dibromosceptrin. Similarly, dibromosceptrin was more effective than clathrodin in
      delaying the time course of current decay. Thus, these two alkaloids appear to be
      new sodium channel neurotoxins acting through different mechanisms,
      dibromosceptrin modifying the channel inactivation characteristics and clathrodin
      probably influencing channel ionic conductance.

PMID- 7570637
TI  - Botulinal neurotoxin C1 complex genes, clostridial neurotoxin homology and
      genetic transfer in Clostridium botulinum.
AB  - The botulinal neurotoxins (BoNT) associate with non-toxic proteins (ANTP) by non
      covalent bonds to form large complexes. In C. botulinum C, the BoNT/C1 locus
      consists of six genes which are organized in three clusters. Cluster 1
      encompasses the genes of BoNT/C1 and ANTP/139 which could be involved in the
      resistance of the BoNT/C1 to the acidic pH and protease degradation. The second
      cluster consists of three genes which encode hemagglutinin components. The last
      gene encodes a DNA binding protein (Orf22) which might regulate the BoNT/C1
      complex gene expression. BoNT and tetanus toxin (TeTx) display similar structure
      and mechanism of action at the molecular level. Their identity at the amino acid
      level range from 34 to 96.8%, indicating that the clostridial neurotoxin genes
      probably derive from a common ancestor. The fact that Clostridium other than C.
      botulinum such as C. butyricum and C. baratii can produce a BoNT suggests that
      the BoNT genes can be transferred between Clostridium strains. The toxigenic C.
      butyricum strains seem to derive from originally non-toxic strains by neurotoxin
      gene transfer from C. botulinum E, probably including a mobile DNA element. In C.
      botulinum C and D the gene encoding the exoenzyme C3 has been localized in a
      transposon-like element of 21.5 kbp. Transposons could be involved in BoNT gene
      transfer in C. botulinum.

PMID- 7570636
TI  - Characterization of a rabbit serum raised against a botulinum toxin type A
      binding protein from presynaptic plasma membranes from Torpedo electric organ.
AB  - Botulinum neurotoxin type A blocks acetylcholine release from the peripheral
      nervous system. We have previously described a putative botulinum neurotoxin type
      A receptor of presynaptic plasma membranes from Torpedo. The electric organ of
      Torpedo, which is largely enriched in cholinergic nerve endings, is homologous to
      the neuromuscular junction, allowing us to isolate large scale of presynaptic
      components. In order to characterize this protein we have raised a polyclonal
      antibody (a-P140) against this receptor. The antiserum a-P140 recognizes a
      140,000 mol. wt band in non-reducing conditions and an 80,000 band in reducing
      conditions. The immunohistochemistry assay reveals the P140 protein on the
      ventral face of the electrocytes where the nerve terminals are localized.
      Moreover, a-P140 antiserum recognizes the P140-BoNT/A complex after binding and
      cross-linking experiments. In addition, we have immunoprecipitated an in vitro
      translated product which is closely coincident in mol. wt to the 80,000 band of
      the receptor.

PMID- 7570635
TI  - The enterotoxin of Clostridium perfringens type A binds to the presynaptic nerve
      endings in neuromuscular junctions of mouse phrenic nerve-diaphragm.
AB  - The enterotoxin of Clostridium perfringens type A, a channel-pore forming protein
      toxin, inhibited neuromuscular transmission in isolated mouse phrenic nerve
      diaphragm preparation at low concentrations of calcium. We investigated
      immunohistochemically the localization of the binding sites of the enterotoxin in
      the preparation under the conditions in which the enterotoxin reduced maximally
      the amplitudes of the twitch tension elicited by electrical stimulations to the
      phrenic nerve. Under the conditions, double immunohistochemical staining of the
      preparation with (1) rabbit anti-enterotoxin IgG-rhodamine-labeled goat anti
      rabbit IgG and (2) mouse anti-synaptophysin (one of the synaptic vesicle-specific
      membrane proteins)-fluorescein isothiocyanate (FITC)-labeled goat anti-mouse IgG
      showed that the enterotoxin binds specifically to most of the sites which were
      stained with anti-synaptophysin exactly in the same configurations having the
      shapes of the nerve endings in the endplates. The thin section electron
      micrographs of the enterotoxin-intoxicated preparation showed no alterations in
      the ultrastructure of the neuromuscular junction and the nerve endings filled
      with numerous synaptic vesicles. The present results, together with our previous
      electrophysiological findings, indicate that the enterotoxin binds specifically
      to the presynaptic nerve endings and inhibits neurotransmitter release at the
      neuromuscular junction.

PMID- 7570639
TI  - Interactions between heavy metal chelators and botulinum neurotoxins at the mouse
      neuromuscular junction.
AB  - Exposure of isolated mouse hemidiaphragms to botulinum neurotoxins, 0.1 nM BoNT-A
      or BoNT-B, at 36 degrees C reduced nerve-elicited peak isometric twitch tension
      to 50% of control values at 55 min (BoNT-A) to 68 min (BoNT-B) after application.
      Either coincubation of BoNT with the heavy metal chelator TPEN, preincubation
      with TPEN followed by BoNT, or application of TPEN after BoNT but before
      neuromuscular block, delayed the onset of muscle failure in a dose-dependent
      manner by up to five-fold. TPEN doses between 2 and 10 microM were required to
      antagonize significantly the muscle block produced by BoNT, and the delay in
      onset was maximal between 10 and 50 microM TPEN. Treatment of muscles with a
      Zn(2+)-TPEN coordination complex, rather than TPEN alone, eliminated any
      beneficial effects of TPEN on BoNT intoxication, indicating that these effects
      were mediated by chelation of Zn2+. Other metal chelators that were not as
      membrane permeant as TPEN were ineffective in delaying BoNT paralysis, suggesting
      that TPEN acts by chelating intraterminal Zn2+. In the absence of BoNT, TPEN
      caused a dose-dependent increase in nerve-elicited twitch tension with a half
      maximal concentration at 8 microM. There was no corresponding change in twitches
      from direct electrical stimulation of the muscle. After BoNT (A or B serotype)
      had reduced the muscle twitch by 20 to 70%, however, subsequent application of
      TPEN rapidly depressed nerve-elicited twitches. The shift from potentiation to
      depression after BoNT treatment suggests that presynaptic vesicle mobilization
      and/or release involve Zn(2+)-dependent enzymes and that BoNTs interact with
      these enzyme pathways.

PMID- 7570638
TI  - Antagonism of botulinum toxin-induced muscle weakness by 3,4-diaminopyridine in
      rat phrenic nerve-hemidiaphragm preparations.
AB  - The effects of the potassium channel inhibitor and putative botulinum toxin
      antagonist 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the
      contractile properties of rat diaphragm muscle. In the presence of 100 pM
      botulinum neurotoxin A (BoNT/A), twitches elicited by supramaximal nerve
      stimulation (0.1 Hz) were reduced to approximately 10% of control in 3 hr at 37
      degrees C. Addition of 3,4-DAP led to a rapid reversal of the BoNT/A-induced
      depression of twitch tension. In the presence of 100 microM 3,4-DAP, antagonism
      of the BoNT/A-induced blockade began within 30-40 sec and reached 82% of control
      with a half-time of 6.7 min. The beneficial effect of 3,4-DAP was well maintained
      and underwent little or no decrement relative to control for at least 8 hr after
      addition. Application of 1 microM neostigmine 1 hr after 3,4-DAP led to a further
      potentiation of twitch tension, but this action lasted for < 20 min. Moreover,
      neostigmine caused tetanic fade during repetitive stimulation. In contrast to the
      efficacy of the parent compound, the quaternary derivative of 3,4-DAP, 3,4
      diamino-1-methyl pyridinium produced little or no twitch potentiation up to a
      concentration of 1 mM. The potassium channel blocker, tetraethylammonium,
      generated a transient potentiation followed by a sustained depression of twitch
      tensions. It is concluded that 3,4-DAP is of benefit in antagonizing the muscle
      paralysis following exposure to BoNT/A. Co-application of neostigmine or
      tetraethylammonium with 3,4-DAP, however, appears to confer no additional
      benefit.

PMID- 7570641
TI  - Structural predictions of the channel-forming region of botulinum neurotoxin
      heavy chain.
AB  - A novel combination of theoretical approaches was exploited to predict which
      amino acid residues of various botulinum neurotoxin serotypes participate in
      forming ion channels. Estimates of sequence hydrophobic moments were used
      initially to identify residues within amphipathic regions in the N-terminal half
      of the heavy chain. A neural network algorithm was then used to make additional
      secondary structural predictions for these regions. Together, these approaches
      predicted a complimentary pattern of four, adjacent amphipathic, possibly
      transmembrane, regions that may be separated by solvent-exposed loops. Both the
      hydrophobic moment and the neural net analyses predicted that at least one of
      these amphipathic segments may be in an extended conformation. These theoretical
      results are discussed in view of our current knowledge of other transmembrane
      structures.

PMID- 7570640
TI  - A study of zinc-dependent metalloendopeptidase inhibitors as pharmacological
      antagonists in botulinum neurotoxin poisoning.
AB  - Zinc-dependent metalloprotease inhibitors phosphoramidon, captopril and a peptide
      hydroxamate were studied as potential pretreatment compounds by examining their
      ability to delay the onset or to prolong the time to 50% block of nerve-elicited
      muscle twitch tension in the mouse phrenic-nerve diaphragm (in vitro at 36
      degrees C) after botulinum neurotoxin serotypes A and B (BoNT-A, BoNT-B).
      Addition of BoNT-A or BoNT-B (1 x 10(-10) M) produced 50% block of the twitch
      response at 56 +/- 9 min and 76 +/- 4 min, respectively. Preincubation (45 min)
      of muscles with phosphoramidon (0.2 mM) prolonged the time to 50% block by 15 min
      in BoNT-B-poisoned muscles with no effect on the time-course of paralysis in BoNT
      A exposed muscles. When the same quantities of BoNT-A or BoNT-B (equivalent to 1
      x 10(-10) M bath concentration) were preincubated for 2 hr with phosphoramidon
      (equivalent to 0.2 mM final bath concentration), and the incubation mixture was
      added to the muscle chamber, the times to 50% block were prolonged by 38 min and
      18 min for BoNT-B and BoNT-A, respectively. Preincubation of diaphragms with
      captopril (up to 10 mM) or peptide hydroxamate (75 microM) failed to antagonize
      BoNT-A or BoNT-B-induced neuromuscular block. Among the three metalloprotease
      inhibitors examined here, only phosphoramidon showed a significant protection
      against both serotypes of BoNT. A search for better inhibitor compounds
      specifically tailored to match the active site on BoNT molecule deserves
      attention.

PMID- 7570644
TI  - Eurotox '95. 34th European Congress of Toxicology. Prague, Czech Republic, 27-30
      August 1995. Abstracts.

PMID- 7570645
TI  - Proceedings of the 1993 Decision Support Methodologies International Workshop,
      Agency for Toxic Substances and Disease Registry. Atlanta, Georgia, USA, 18-20
      October 1993.

PMID- 7570643
TI  - Neural cell adhesion molecule (N-CAM) distribution may predict the effect of
      neurotoxins on the brain.
AB  - The neural cell adhesion molecule (N-CAM) is a convenient neurospecific marker
      for investigating the effects of neurotoxins on cell migration, cell recognition
      and differentiation of neurons during development. In this report, we discuss the
      developmental toxicity of valproic acid studied by two different approaches (the
      immunochemical detection of N-CAM content and polypeptide composition, and
      immunohistochemical analysis of N-CAM topography). Immunohistochemical analysis
      of distribution of N-CAM as a surface marker on the neural cells predicted the
      effect of the neurotoxin.

PMID- 7570646
TI  - Achieving credibility in risk assessment models.
AB  - Validation of a mathematical model requires demonstrating that a model is free of
      mathematical errors (internal consistency), is sensitive to large but not small
      errors or uncertainties in parameter values (verifiability and robustness),
      reproduces experimental observations on the system being modeled (external
      consistency), and leads to testable predictions of the system's biological
      properties. To be heuristically valid, a model also must be a realistic
      representation of the actual biological system. Only then would the model's
      predictions be credible to the wider community of biological scientists who would
      use the model for risk assessment and dose or species extrapolation. Owing to
      incomplete data, most current dosimetric models are insufficiently realistic to
      pass this test of credibility. Enhancements to such models that would help
      achieve credibility are presented, and suggestions are offered for
      institutionalizing realistic modeling practices in risk assessment.

PMID- 7570642
TI  - Alteration in the glial cell metabolism of glutamate by kainate and N-methyl-D
      aspartate.
AB  - Incubation of coronal slices of rat brain with neurotoxic concentrations of
      kainate (300 microM) and N-methyl-D-aspartate (NMDA; 500 microM) for 40 min
      reduced the activity of the glial enzyme, glutamine synthetase, by 33% and 21%,
      respectively. The immunoreactivity of the neuronal enzyme, gamma gamma-enolase
      (neuron-specific enolase), was also decreased, but to a lesser extent than
      glutamine synthetase. Pre-incubation of the slices with L-methionine-S
      sulphoximine (500 microM), an irreversible inhibitor of both glutamine synthetase
      and gamma-glutamylcysteine synthetase, before addition of either kainate or NMDA
      produced a supra-additive reduction in the activity of the enzyme in both cases.
      Neither kainate nor NMDA directly inhibited the activity of glutamine synthetase,
      but kainate did inhibit gamma-glutamylcysteine synthetase, a rate-limiting enzyme
      of the gamma-glutamyl cycle, which is responsible for maintaining glutathione
      levels within cells. Pre-incubation of the slices with L-NG-nitroarginine, a
      competitive inhibitor of nitric oxide synthase, effectively prevented the NMDA
      induced reduction in glutamine synthetase and neuron specific enolase, but did
      not diminish the kainate-induced decrease in the activity of either enzyme. These
      results provide evidence that NMDA, as well as kainate, indirectly affects the
      activity of glutamine synthetase in brain slices, yet does so by a different
      mechanism from kainate. The results are discussed in terms of the possible mode
      of action of each toxin in inhibiting the glial cell metabolism of glutamate.

PMID- 7570647
TI  - ATSDR's information databases to support human health risk assessment of
      hazardous substances. Agency for Toxic Substances and Disease Registry.
AB  - The American public, like persons in many other nations, is concerned about the
      potential adverse impacts of uncontrolled hazardous wastes. The concerns are
      often predicated on the fear that adverse health effects will occur because of
      releases of hazardous substances into community environments. To respond to these
      concerns, government agencies and private sector organizations must rely on
      credible, accessible, up-to-date information databases. These databases should be
      relevant to the needs of the people who respond to uncontrolled releases of
      hazardous substances. Of particular importance are databases that profile the
      toxicity of hazardous substances and other information useful to physicians and
      other health care providers. This paper describes how the federal Agency for
      Toxic Substances and Diseases Registry (ATSDR) has developed several toxicologic
      and human health information databases under mandates in the Superfund statute
      for responding to the public's concerns about hazardous substances.

PMID- 7570649
TI  - Threshold of estimated toxicity for regulation of indirect food additives.
AB  - In response to the objectives of this ATSDR workshop, 2 new procedures are
      described for assessing the safe use of indirect food additives. First, this
      workshop provided a timely forum in which to describe a newly proposed Threshold
      of Regulation (T/R) Policy under which the Food and Drug Administration (FDA)
      would exempt certain indirect food additives from the formal premarket petition
      process. Second, this workshop offered an opportunity to discuss 2 circumstances
      in which Quantitative Structure Activity Relationship (QSAR) methodologies might
      be utilized in the future to provide decision-support information for substances
      used in food-contact articles.

PMID- 7570648
TI  - Role of computational chemistry in support of hazard identification (ID):
      mechanism-based SARs.
AB  - A mechanism-based structure-activity relationship (SAR) study examines the
      structural basis for a chemical/biological activity by targeting a single or a
      few stages in a postulated mechanism of action. Computational chemistry
      approaches provide a valuable complement to experiment for probing such
      associations, but require a highly focused viewpoint that neglects much of the
      full biological and chemical interaction problem. Research questions are
      formulated in terms of fundamental structure and reactivity properties and are
      designed to test key assumptions of a postulated mechanism of activity. The
      results of such studies can aid in the generation of new hypotheses, suggest new
      experiments, and provide scientific rationale for extrapolation in hazard
      identification (ID). Toxicologists and computational chemists bring very
      different, yet complementary viewpoints, approaches, and expertise to bear on the
      hazard ID problem. However, improved communication and interaction between these
      two groups is needed to most productively address hazard ID issues.

PMID- 7570650
TI  - Assessment of effect levels of chemicals from quantitative structure-activity
      relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level
      (LOAEL).
AB  - With the multitude of new chemicals being synthesized and the paucity of long
      term test data on chemicals that could be introduced into the environment,
      innovative approaches must be developed to determine the health and environmental
      effects of chemicals. Research was conducted to employ quantitative structure
      activity relationship (QSAR) techniques to study the feasibility of developing
      models to estimate the noncarcinogenic toxicity of chemicals that are not
      addressed in the literature by relevant studies. A database of lowest-observed
      adverse effect level (LOAEL) was assembled by extracting toxicity information
      from 104 U.S. EPA documents, 124 National Cancer Institute/National Toxicology
      Program (NCI/NTP) reports, and 6 current reports from the literature. A
      regression model, based on 234 chemicals of diverse structures and chemical
      classes including both alicyclic and aromatic compounds, was developed to assess
      the chronic oral LOAELs in rats. The model was incorporated into an automated
      computer package. Initial testing of this model indicates it has application to a
      wide range of chemicals. For about 55% of the compounds in the data set, the
      estimated LOAELs are within a factor of 2 of the observed LOAELs. For over 93%,
      they are within a factor of 5. Because of the paucity or absence of long-term
      toxicity data, the public health and risk assessment community could utilize such
      QSAR models to determine initial estimates of toxicity for the ever-increasing
      numbers of chemicals that lack complete pertinent data. However, this and other
      such models should be used only by expert toxicologists who must objectively look
      at the estimates thus generated in light of the overall weight of evidence of the
      available toxicologic information of the subject chemical(s).

PMID- 7570651
TI  - Toxicity estimation by chemical substructure analysis: the TOX II program.
AB  - The objectives of our work are to develop methodologies capable of identifying
      the potential environmental health hazards of chemicals. These techniques are
      particularly useful when it is necessary to evaluate molecules that have not been
      synthesized as yet, or for which there is little or no toxicological information
      known. With the help of MULTICASE, an artificial intelligence program capable of
      uncovering the relationship between the presence of specific substructures in a
      molecule and its toxicity, and TOX II, a program capable of identifying the
      existence of such substructures in a new molecule, it is now possible to predict
      with a reasonable degree of certainty whether a new molecule will be toxic. TOX
      II will uncover any functionality previously found to be related to toxicity in
      any organic molecule. The evaluation is extensive and may include its
      automatically generated metabolites. The scope of TOX II is vast as more than 70
      toxicological endpoints can be evaluated.

PMID- 7570652
TI  - A thermodynamic QSAR analysis of the polysubstrate monooxygenase responses to
      xenobiotic chemicals.
AB  - Empirical quantitative structure activity relationships (QSAR) predict risk from
      exposure to xenobiotic chemicals as a dependence of inverse concentration on oil
      water partition and electronic structural factors. This is equivalent, term by
      term to standard kinetic molecular transition state theory. When this transformed
      version is applied to the behaviour of the polysubstrate monooxygenase (PSMO)
      enzyme system, the rate of unintended behaviour depends directly on only two
      electronic factors. One is negative dependence on the strength of the weakest
      carbon-hydrogen (C-H) bond, a factor common to both ionic and free radical
      mechanisms. The second is a strong negative dependence on the polarization of
      this bond towards positive charge on the carbon, a factor relevant to ionic
      reactions. The risk of unintended oxidation reactions, in contrast, depends
      directly on these two factors because as the rate of intended hydroxylation is
      inhibited by strong or polar C-H bonds, alternative essentially 'accidental'
      oxidations occur. These are shown to lead to several different disease end points
      depending on the ratio of C-H bond strength to polarity.

PMID- 7570654
TI  - The application of dosimetry models to identify key processes and parameters for
      default dose-response assessment approaches.
AB  - Mathematical dosimetry models should improve the accuracy of various
      extrapolations required in dose-response assessment because they include explicit
      descriptions of the major mechanistic determinants of the exposure-dose-response
      continuum. The availability of these anatomic and physiologic parameters for
      different mammalian species (including humans) and the physicochemical parameters
      for individual chemicals is an important consideration in the formulation of
      model structures and the application of simplifying assumptions to develop
      default models. A framework is presented that includes iterative development of
      model structures as more data become available. Development of the default
      dosimetry adjustments for interspecies extrapolation used in the inhalation
      reference concentration (RfC) methods of the U.S. Environmental Protection Agency
      (EPA) is discussed as an example of iterative model development, a process
      intended to ensure that model structures are commensurate with available data.
      The framework also aids evaluation of different model structures and can be
      applied to identify key parameters. Examples are provided to illustrate how
      insight on the key mechanistic determinants of exposure-dose-response can guide
      interpretation of data in the absence of comprehensive model structures, identify
      gaps in the database for a given chemical, or direct data gathering for chemicals
      that are yet to enter production.

PMID- 7570653
TI  - Risk assessment and research: an essential link.
AB  - Regulatory agencies, such as the U.S. Environmental Protection Agency, use health
      risk assessment information in developing pollution control regulations and for
      setting regulatory and research priorities. The risk assessment process, however,
      is hampered by limitations in test methods, in models for exposure and dose
      response, and by chemical-specific data gaps. The research/risk assessment/risk
      management framework provides opportunities for targeting and coordinating
      research to address these limitations. Enhanced communication among researchers,
      risk assessors and risk managers to foster better development and use of
      scientific information in decision making, and incentives for interdisciplinary
      research efforts, are needed.

PMID- 7570655
TI  - The application of physiologically based pharmacokinetic/pharmacodynamic
      (PBPK/PD) modeling to understanding the mechanism of action of hazardous
      substances.
AB  - Much of toxicology research is focused on elucidating the nature of the
      mechanisms through which various xenobiotics exert their toxic effects. The
      central issue in extrapolating laboratory experiments to the human situation is
      whether mechanisms which are operative in laboratory animals are similar to
      mechanisms operating in humans. The underlying assumption is that understanding
      mechanisms permits rational extrapolation between species, across routes of
      exposure, or from high to low doses. There are two general classes of mechanisms
      of action. First, there are the mechanisms that result in the translation of an
      exposure concentration to the effective dose at the target site. The mechanisms
      that are operative at a pharmacokinetic level include those that are
      physiologically driven and those that are metabolically based. Second are
      mechanisms through which the dose at the target site elicits the ultimate adverse
      response. These are pharmacodynamic in nature and refer to the action of the
      effective dose at the target site. Altered gene regulation, cytotoxicity, and
      cell proliferation are examples of processes involving potential adverse effects
      at the target site. A quantitative understanding of the mechanisms involved in
      going from exposure to dose and dose to response can aid in answering the
      question of whether or not these mechanisms in animals and humans are similar or
      different.

PMID- 7570656
TI  - The application of physiologically based pharmacokinetic/pharmacodynamic
      (PBPK/PD) modeling for exploring risk assessment approaches of chemical mixtures.
AB  - When dealing with health impacts of environmental or occupational exposure such
      as groundwater contamination from or remediation effort associated with hazardous
      waste sites, we are obviously not facing individual, single chemicals. Thus, we
      are immediately confronted with the following questions: (1) Is single chemical
      risk assessment approach applicable to the multiple chemicals in hazardous waste
      sites? (2) How do we handle risk assessment of chemical mixtures? Although there
      were pioneering and commendable efforts from the USEPA to formulate guidelines
      for risk assessment of chemical mixtures, these guidelines were principally based
      on additivity concept. As new scientific advances are made, improvement and
      refinement of risk assessment methodology will be anticipated. At Colorado State
      University (CSU), our research effort is devoted to the challenges and potential
      applications of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD)
      modeling in the risk assessment of chemical mixtures. With the ultimate goal of
      Predictive Toxicology, 3 specific research projects are described: (1) PBPK/PD
      modeling of toxicologic interactions between trichloroethylene (TCE) and 1,1
      dichloroethylene (1,1-DCE) and the investigation and defining of an 'Interaction
      Threshold'; (2) PBPK/PD modeling of toxicologic interactions between Kepone and
      carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the
      prediction of acute toxicity; (3) PBPK modeling of the inhibition of
      pharmacokinetics and enzyme kinetics of TCE caused by low-level, repeated dosing
      of a chemical mixture of 7 groundwater contaminants. Since this paper is meant to
      be a commentary and the emphasis is on approaches for dealing with chemical
      mixtures, detailed presentation of data is avoided. These examples illustrate
      partially our ongoing research activities and the related ideas with respect to
      possible novel risk assessment applications to chemical mixtures.

PMID- 7570657
TI  - Summary of panel discussion on the 'advantages/limitations/uncertainties in the
      use of physiologically based pharmacokinetic and pharmacodynamic models in hazard
      identification and risk assessment of toxic substances'.
AB  - A panel of scientists discussed a variety of issues related to the development of
      physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models for
      toxicological risk assessment. The panel concluded that although there are a
      variety of potential technical problems associated with the use of these models
      for hazard identification and risk assessment, PBPK/PD modeling represents an
      important technical advance in risk assessment methodology that should continue
      to be developed and applied. In addition to the technical issues that were
      addressed, the necessity of providing additional education for toxicologists in
      the skills necessary for the development and evaluation of PBPK/PD models was
      stressed.

PMID- 7570658
TI  - The application of physiologically based pharmacokinetic modeling in human health
      risk assessment of hazardous substances.
AB  - Physiologically based pharmacokinetic (PBPK) modeling is an important tool for
      improving the accuracy of human health risk assessments for hazardous substances
      in the environment. The proper use of PBPK modeling can reduce uncertainties that
      currently exist in risk assessment procedures by providing more scientifically
      credible extrapolations across species and routes of exposure, and from high
      experimental doses to potential environmental exposures. Current applications of
      PBPK models range from relatively straightforward uses for the extrapolation of
      chemical kinetics across species, route, and duration of exposure to much more
      demanding chemical risk assessment applications requiring a description of
      complex pharmacodynamic phenomena such as mitogenicity and hyperplasia secondary
      to cytotoxicity. PBPK modeling helps to identify the factors that are most
      important in determining the health risks associated with exposure to a chemical,
      and provides a means for estimating the impact of those factors both on the
      average risk to a population and on the specific risk to an individual. The chief
      challenge in the application of PBPK modeling in human health risk assessment
      lies in the need to generate chemical-specific data to support the development
      and validation of the models. Extensive use of rapidly developing in vitro and
      structure-activity relationship techniques is needed to provide the data required
      for the large number of hazardous chemicals currently contaminating the
      environment.

PMID- 7570659
TI  - Development of structure-activity relationship rules for predicting carcinogenic
      potential of chemicals.
AB  - Since the inception of Section 5 (Premanufacturing/Premarketing Notification,
      PMN) of the Toxic Substances Control Act (TSCA), structure-activity relationship
      (SAR) analysis has been effectively used by U.S. Environmental Protection
      Agency's (EPA) Structure Activity Team (SAT) in the assessment of potential
      carcinogenic hazard of new chemicals for which test data are not available. To
      capture, systematize and codify the Agency's predictive expertise in order to
      make it more widely available to assessors outside the TSCA program, a
      cooperative project was initiated to develop a knowledge rule-based expert system
      to mimic the thinking and reasoning of the SAT. In this communication, we
      describe the overall structure of this expert system, discuss the scientific
      bases and principles of SAR analysis of chemical carcinogens used in the
      development of SAR knowledge rules, and delineate the major factors/rules useful
      for assessing the carcinogenic potential of fibers, polymers, metals/metalloids
      and several major classes of organic chemicals. An integrative approach using
      available short-term predictive tests and non-cancer toxicological data to
      supplement SAR analysis has also been described.

PMID- 7570660
TI  - Quantitative structure-activity relationships and ecological risk assessment: an
      overview of predictive aquatic toxicology research.
AB  - In the field of aquatic toxicology, quantitative structure-activity relationships
      (QSARs) have developed as scientifically credible tools for predicting the
      toxicity of chemicals when little or no empirical data are available. A
      fundamental understanding of toxicological principles has been considered an
      important component to the acceptance and application of QSAR approaches as
      biologically relevant in ecological risk assessments. As a consequence, there has
      been an evolution of QSAR development and application from that of a chemical
      class perspective to one that is more consistent with assumptions regarding modes
      of toxic action. In this review, techniques to assess modes of toxic action from
      chemical structure are discussed, with consideration that toxicodynamic knowledge
      bases must be clearly defined with regard to exposure regimes, biological
      models/endpoints and compounds that adequately span the diversity of chemicals
      anticipated for future applications. With such knowledge bases, classification
      systems, including rule-based expert systems, have been established for use in
      predictive aquatic toxicology applications. The establishment of QSAR techniques
      that are based on an understanding of toxic mechanisms is needed to provide a
      link to physiologically based toxicokinetic and toxicodynamic models, which can
      provide the means to extrapolate adverse effects across species and exposure
      regimes.

PMID- 7570661
TI  - Information needed to support hazard identification and risk assessment of toxic
      substances.
AB  - Today pharmacokinetic data are not routinely required for food safety evaluation.
      The new Red Book, the Center's outline of animal testing protocols, does suggest
      some pharmacokinetic studies, but their use is still limited. Primarily this is
      because of our current reliance on animal studies only and the use of safety
      factors (SFs) to bridge the human to animal response. But the situation is
      changing and the role of pharmacokinetics and physiologically based
      pharmacokinetic modeling will probably increase for several reasons. (1) The
      increasing role of quantitative risk assessment and regulations acknowledging and
      permitting some level of risk. This places a demand of greater quantitation of
      risk and emphasizes the need for better measurement of effective dose. We made
      need to consider more carefully the possible nonlinear pharmacokinetic effects in
      high-to-low dose extrapolation. (2) The increasing need to understand more about
      a chemical's mechanism of action prior to a major corporate commitment. The
      increasing cost of mistakes in judgement regarding a chemical's prospects in the
      commercial and regulatory arena are demanding a better and deeper understanding
      of possible toxic effects. (3) The increasing desire to expand the use of a
      successful additive beyond the spectrum of the uses covered in the original
      approval. This usually means the request for a higher ADI. This must be based on
      more refined toxicity testing and better estimate of effective dose in order to
      permit the reduction of the SF. (4) The advent of novel foods for which
      conventional toxicological methods are inappropriate. For example, noncaloric fat
      substitutes that may comprise a large portion of the daily diet cannot adequately
      be tested in conventional animal studies. The doses cannot be exaggerated enough
      to permit a large enough SF. These substances may well require human clinical
      investigations similar to those used for drugs.

PMID- 7570662
TI  - Use of graph theoretic parameters in risk assessment of chemicals.
AB  - In many instances of risk assessment, one has to estimate the potential risk of
      chemicals using limited experimental data, or no empirical data at all. In such
      cases, the use of non-empirical parameters, which can be calculated directly from
      structure, is a viable option for the risk assessor. Graph invariants have been
      used in predicting properties of congeneric sets of chemicals and determining
      structural similarity/dissimilarity of molecules. In this paper we have used (a)
      topological parameters in predicting mutagenicity of a diverse set of 520
      chemicals and (b) graph theoretic parameters in quantifying structural similarity
      for a selection of analogs. The results of these analyses are presented along
      with a critical discussion of the utility and limitations of these methods.

PMID- 7570663
TI  - The identification and testing of interaction patterns.
AB  - This paper presents a method for identifying and assessing the significance of
      interaction patterns among various chemicals and chemical classes of importance
      to regulatory toxicologists. To this end, efforts were made to assemble and
      evaluate experimental data on toxicologically significant interactions, to use
      this information to characterize the consistency of toxicological interactions,
      and to define classes of compounds that display similar toxicological
      interactions. The motivation for this effort is to be able to propose hypotheses,
      which can be validated by experimentation, on how 2 or more chemicals will
      interact.

PMID- 7570664
TI  - Summary and recommendations for session B: activity classification and structure
      activity relationship modeling for human health risk assessment of toxic
      substances.
AB  - The major theme of Session B explored and assessed the current status of activity
      classification (AC)1 and structure-activity-relationship (SAR) methods developed
      to model adverse health effects that can result when biological systems are
      exposed to various chemical substances. The output from such models is intended
      to be used as information that supports risk assessments performed on toxic
      substances. Speakers gave special attention to the requirements and applications
      of hazard identification models. Specific aspects of the broad subject matter
      were augmented and explicated by audience and panel discussions during the 1.5
      days available. This format stimulated the exchange of a surprisingly broad range
      of information and stimulating ideas. In order to gather the diverse aspects of
      Session B in one place, the Rapporteurs agreed that this summary would aim at
      providing a comprehensive overview, while Dr. Feldman's would amplify selected
      points of general interest.

PMID- 7570666
TI  - NIEHS perspectives on collaboration among government, academia, and industry.

PMID- 7570667
TI  - Use of mechanistic and pharmacokinetic data for risk assessment at the National
      Institute of Environmental Health Sciences (NIEHS).
AB  - In summary, the National Institute of Environmental Health Sciences (NIEHS) and
      the National Toxicology Program (NTP) have been important contributors of data
      for hazard identification, including toxicological data as well as mechanistic
      and pharmacokinetic information. One of the factors that limits the use of
      knowledge is our lack of understanding of the animal test models currently in
      use. The underlying bases for regulatory controls that account for normal
      physiological functions are often not well understood. As a result, toxicological
      data tend to be used in an empirical manner rather than a manner based on
      mechanistic understanding. Continued testing of chemicals and random generation
      of data have their limits in improving our predictive abilities. Attention must
      be given to prioritizing studies on the basis of critical gaps in understanding
      that are needed to build knowledge bases in the future.

PMID- 7570668
TI  - Program development in military toxicology laboratories.
AB  - Military toxicology evolved from needs identified during the World Wars. The
      Army, Navy and Air Force developed toxicological capabilities in response to
      their respective operational needs. These 3 previously separate military
      toxicology efforts have been integrated into Tri-Service Toxicology in response
      to the continually changing and growing operational needs of the military. The
      continual process of program development must be initiated in order for Tri
      Service Toxicology to improve, grow and better serve its customers. Program
      development entails developing and maintaining good customer relationships and
      cooperative relationships with other governmental agencies, industry and
      academia. The benefits of identifying and obtaining customers and collaborators
      will substantially outweigh the costs incurred by committing to the
      implementation of program development within Tri-Service Toxicology.

PMID- 7570669
TI  - Perspectives on collaboration and infrastructure development among government,
      academia, and industry.

PMID- 7570665
TI  - Decision support methodologies for human health assessment of toxic substances:
      Agency for Toxic Substances and Disease Registry's perspectives on collaboration
      and infrastructure development among government, academia, and industry.
AB  - ATSDR's mission is to prevent or mitigate adverse human effects and diminished
      quality of life that result from exposure to hazardous substances from hazardous
      waste sites, unplanned releases, and other sources of pollution present in the
      environment. As part of this charge, human health assessments are performed
      through the use of data from animal studies environmental monitoring data and
      human epidemiological studies. Often sufficient data are not available to perform
      such assessments. Hence, modeling approaches are often used to estimate the
      likelihood of exposure to environmental chemicals and adverse health effects to
      human populations. In the last two decades, several computational techniques have
      been recognized as having potential to improve the accuracy of this process. As
      part of the assessment process, (1) chemicals of potential concern must be
      identified, (2) available data on their toxicity evaluated, (3) quantitative
      measures of their potential adverse health effects developed, and (4) exposure
      assessments made. The human health risk must then be characterized in a useful
      and understandable manner.

PMID- 7570670
TI  - Extrapolating the future: research trends in modeling.
AB  - The proceedings in this volume suggest several important future research needs.
      Research is needed to validate modeling in toxicology in order to support the use
      of the general approach of modeling, either for structure-activity relationships
      (SAR) or physiologically based pharmacokinetics (PBPK), by regulators. Research
      is needed to demonstrate how SAR predictions can be integrated with the PBPK
      models to reduce the chemical-specific, intensive data requirements of PBPK
      models. Methods are needed to harmonize modeling approaches and to educate
      potential users. New approaches to modeling are needed which go beyond present
      day assumptions of flow-limited models into dynamic models of human health
      effects. The academic community can further these objectives by including applied
      mathematics of toxicology, including both SAR and PBPK modeling, in toxicology
      curricula.

PMID- 7570671
TI  - Perspectives on collaboration and infrastructure development: industry
      perspectives.
AB  - Industry continues to promote the use of sound science in regulatory decision
      making. The use of decision support methodologies for hazard identification/risk
      assessment of toxic substances such as models employing physiologically based
      pharmacokinetics (PBPK) and structure-activity relationships (SAR) are
      recommended. A collaborative program involving government and industry is needed
      to further the use of these decision support methodologies. The formation of
      federal and state working groups is recommended. Organizations such as the
      Halogenated Solvents Industrial Alliance (HSIA), American Industrial Health
      Council (AIHC), and the Chemical Manufacturers Association (CMA) are suitable
      industry representatives.

PMID- 7570672
TI  - Development of physiologically based pharmacokinetic and physiologically based
      pharmacodynamic models for applications in toxicology and risk assessment.
AB  - Pharmacokinetics (PK) involves the study of the rates of absorption,
      distribution, excretion, and biotransformation of chemicals and their
      metabolites. PK models can be used to reconstruct extensive time-course data sets
      based on a small number of kinetic parameters. These models can be used to
      predict the results of new experiments and integrate studies on kinetics,
      disposition and metabolism in various animal species [1]. The 2 main approaches
      that have been pursued in developing PK models are: (1) data-based compartmental
      modeling; and (2) physiologically based compartmental modeling. Data-based models
      rely on the collection of time-course concentration data and fitting these data
      with mathematical models. Compartments in these models do not necessarily reflect
      the anatomy and physiology of the animal, and the kinetic constants derived from
      these models do not have obvious physiological or biochemical counterparts. In
      physiologically based pharmacokinetic (PBPK) models, compartments correspond more
      closely to actual anatomical structures, defined with respect to their volumes,
      blood flows, chemical binding (partitioning) characteristics, and ability to
      metabolize or excrete the compounds of interest. Because the kinetic parameters
      of these models reflect tissue blood flows, partitioning, and biochemical
      constants, these models are more readily scaled from one animal species to
      another [2]. PBPK models have been used to understand the disposition of
      chemicals in the body for almost 70 years. Their more widespread application in
      toxicology dates back only 15 years or so to models developed for polychlorinated
      biphenyls and other persistent lipophilic compounds. Quantitative applications of
      PBPK models in risk assessment date to the development of a number of PBPK models
      for methylene chloride in the mid 1980s. The burgeoning use of PBPK models in
      toxicology research and chemical risk assessment today is primarily related to
      their ability to make more accurate predictions of target tissue dose for
      different exposure situations in different animal species, including humans. This
      overview includes a discussion of the development of these PBPK models in
      toxicology and speculates about future applications of PBPK and physiologically
      based pharmacodynamic (PBPD) models in chemical risk assessment.

PMID- 7570674
TI  - Physiologically based pharmacokinetic and pharmacodynamic modeling in health risk
      assessment and characterization of hazardous substances.
AB  - Recent advances in physiologically based pharmacokinetic and pharmacodynamic
      (PBPK/PD) modeling have introduced novel approaches for evaluating toxicological
      problems. Because PBPK models are amenable to extrapolation of tissue dosimetry,
      they are increasingly being applied to chemical risk assessment. A comprehensive
      listing of PBPK/PD models for environmental chemicals developed to date is
      referenced. Salient applications of PBPK/PD modeling to health risk assessments
      and characterization of hazardous substances are illustrated with examples.

PMID- 7570673
TI  - The expanding role of quantitative structure-activity relationships (QSAR) in
      toxicology.
AB  - Quantitative structure-activity relationships (QSAR) have found wide use in
      correlating the bioactivity of all kinds of organic compounds with all kinds of
      biological entities. So many QSAR have been published that it is time for a new
      phase of study, that of comparative QSAR. From our current database of about 6000
      QSAR illustrative examples are discussed.

PMID- 7570675
TI  - The new chemicals process at the Environmental Protection Agency (EPA): structure
      activity relationships for hazard identification and risk assessment.
AB  - Section 5 of the Toxic Substances Control Act (TSCA) does not require any
      toxicity testing as a prerequisite for submission of a Premanufacturing Notice
      (PMN) for a new chemical. In order to compensate for the lack of actual test
      data, a process involving structure-activity relationships (SAR) for assessing
      hazard potential was constructed. The hazard assessment is then coupled with an
      estimation of potential exposure to determine potential risk. This process
      involves the use of multiple interdisciplinary teams that work within a 90-day
      time frame to complete approximately 2000 risk assessments per year.

PMID- 7570676
TI  - Extrapolation of physiological parameters for physiologically based simulation
      models.
AB  - Masses of organs and fluids, pulmonary ventilation and cardiac output and its
      distribution are the basic input data used in physiologically based
      pharmacokinetic models. Since these parameters are rarely measured in
      pharmacokinetic studies, the values found in reference books or extrapolated to
      meet the specific exposure conditions are used in the models. In this review of
      the extrapolation of pertinent physiological parameters, power equations for
      scaling across mammals, adjustments to body build (lean body mass) and physical
      activity of humans and their significance for risk assessment of human exposure
      to solvents using animal data are assessed.

PMID- 7570678
TI  - Physiologically based pharmacokinetic models: mathematical fundamentals and
      simulation implementations.
AB  - This review paper gives an overview of the building blocks of physiologically
      based pharmacokinetic (PBPK) models and their implementation using computer
      facilities. The approach focuses on the development of a PBPK model with the most
      important and appropriate limiting steps for the conditions and exposure
      scenarios under study. In this approach, the assumptions made in constructing the
      set of equations, as well as the fitting of variables to specific experimental
      results, need to be accounted for when making extrapolation to other conditions.
      A well-constructed PBPK model should account for all possible ranges of
      extrapolation from the development stages so that appropriate experimental
      studies and assumptions can be designed to handle the intended applications. Two
      common assumptions are revisited: the flow-limited assumption and the metabolic
      clearance using Michaelis-Menten kinetics assumption. Computer hardware and
      software requirements for implementing PBPK models are briefly reviewed.

PMID- 7570677
TI  - Development of partition coefficients, Vmax and Km values, and allometric
      relationships.
AB  - A knowledge of the methods used to obtain partition coefficients, Vmax, and Km
      values, and the use of allometric relationships is essential to understanding
      their role in physiologically based pharmacokinetic (PBPK) models. Vial
      equilibration methods for obtaining the partition coefficients of volatile and
      nonvolatile compounds were presented using the results from studies with p
      chlorobenzotrifluoride (PCBTF) and isofenphos, respectively. Partition
      coefficients for volatile and nonvolatile compounds from published studies were
      included. Several published in vivo inhalation (gas uptake) studies and in vitro
      enzyme studies were presented to demonstrate several methods for obtaining Vmax
      and Km values. Allometric equations used in PBPK models for body weight scaling
      of respiration and cardiac rates between species were presented along with
      equations for within species body weight scaling of Vmax.

PMID- 7570679
TI  - Production and properties of mouse monoclonal anti-adriamycin antibody.
AB  - Eight mouse IgG1 monoclonal anti-Adriamycin antibodies were produced in culture
      and in ascites in BALB/c nude mice. The binding constant and specificity was
      measured by an inhibition ELISA method. The assay was an indirect method using
      horseradish peroxidase-labeled goat Fab' antibody and 2mM ABTS (2,2'-azino-bis (3
      ethylbenzthiazoline-6-sulfonic acid) containing 2.5 mM H2O2 as a color reaction
      reagent. The binding constant of the antibodies was 10(6) to 10(8) M-1. The
      antibodies possessed different specificities and affinities to the adriamycin.
      Though adriamycin is a low molecular weight (M.W. 579.99) hapten antigen, it
      possesses several epitopes as antigenic determinant sites. The antigenic epitopes
      of the adriamycin, which until recently were unknown, were analyzed by the
      monoclonal antibodies.

PMID- 7570680
TI  - Nephrotic syndrome associated with subacute bacterial endocarditis (SBE): a case
      report.
AB  - We experienced a female nephrotic patient associated with subacute bacterial
      endocarditis. Her proteinuria was completely normalized after antibiotic therapy
      and valve replacement. Immunofluorescence and an electron microscopic study of a
      renal biopsy specimen showed little evidence of immune complex in the glomeruli.
      Marked deposition of properdin in the glomeruli and the reduced level of serum
      complement may indicate involvement of the complement system in the pathogenic
      mechanism of massive proteinuria in this case.

PMID- 7570681
TI  - Sudden death of a cocaine abuser.
AB  - We report an autopsy case of a 28-year-old male who died after intravenous use of
      cocaine. Cocaine and ecgonine methyl ester, the major metabolite of cocaine, were
      detected in the blood with gas chromatography/mass spectrometry. Postmortem
      examination showed contraction band necrosis together with patchy fibrosis and
      inflammatory cell infiltration in the heart. The sudden death appeared to be
      caused by a cardiac disorder associated with arrhythmia or coronary
      vasoconstriction.

PMID- 7570682
TI  - Surgical treatment of infective endocarditis.
AB  - From February, 1975 through October, 1990, 26 patients underwent surgical
      treatment for infective endocarditis at Tokai University Hospital. The overall
      operative mortality rate was 11.5% (3/26). The three patients who died were
      suffering from aortic prosthetic valve endocarditis (PVE) in the active stage.
      Among 16 patients in the active stage, the mortality rate was 18.7% (3/16) Among
      10 patients with native valve endocarditis (NVE) in the healed stage, all
      survived. Among the total of 21 patients with NVE, the mortality rate was zero
      and among those with PVE, the rate was 60% (3/5). Various species of streptococci
      were the most common organisms encountered, followed by Staphylococcus
      epidermides. The two PVE patients with S. epidermides died. Nine of the 11 NVE
      cases in the active stage were of the localized type. Only one case of the
      localized type of PVE suffered from an infected mitral bioprosthetic valve. The 6
      extensive-type cases had aortic valve endocarditis (2NVE, 4PVE). Three patients
      with the extensive type of PVE died. We conclude that patients with infective
      endocarditis who develop progressive congestive heart failure, recurrent
      embolization, or progressive sepsis despite antimicrobial treatments, should
      undergo prompt valve replacement within 7 days after institution of therapy.

PMID- 7570683
TI  - Effect of time of carbohydrate ingestion on muscle glycogen resynthesis after
      exhaustive exercise in rats.
AB  - We studied the optimal time of carbohydrate ingestion required to restore muscle
      glycogen storage after exhaustive exercise in rats. The animals were divided into
      4 groups (IN0, IN30, IN60 and IN120), each receiving 30% glucose solution (30
      g/kg body weight) through a stomach tube 0, 30, 60 or 120 minutes after exercise.
      Six hours after administration of glucose, the glycogen concentration in the m.
      extensor digitorum longus returned to the baseline in the IN0 group, while
      reaching only 77%, 80% and 73% of the baseline in the IN30, IN60 and IN120
      groups, respectively. There was a significant difference in this variable between
      the IN0 group and any of the three other groups. On the other hand, the glycogen
      concentration in the m. soleus returned to the baseline in all groups with no
      difference. These findings suggest that muscle glycogen may be most efficiently
      resynthesized if carbohydrate is given immediately after exercise, and that
      muscle glycogen resynthesis may vary with the type of muscle.

PMID- 7570684
TI  - Potentiation of neuromuscular blockade by calcium channel blockers.
AB  - A significant reduction was noticed in the amount of vecuronium needed to
      maintain steady neuromuscular blockade at 20% twitch height (T1) in patients
      given nicardipine intraoperatively. Bolus injection of either nicardipine or
      diltiazem during constant infusion of vecuronium produced transient depression of
      T1 and the train-of-four ratio (TOFR). Reversal of neuromuscular blockade with a
      choline esterase inhibitor (neo-stigmine) was not retarded by previous
      administration of Ca-channel blockers but concurrent administration of
      anticholine-esterase agent and Ca-channel blockers caused a delay in recovery
      from motor blockade. Monitoring of neuromuscular junction activity is strongly
      recommended whenever a large cumulative dose of Ca-channel blockers is used.

PMID- 7570685
TI  - Effect of the adrenergic beta 3-agonist, BRL37344, on heat production by brown
      adipocytes in obese and in older rats.
AB  - Heat production by isolated brown adipocytes, from hypothalamic obese rats and
      from older rats, was investigated by microcalorimetry. The obese and older rats
      were 12 and 40 weeks-old, respectively. The basal heat production by the brown
      adipocytes was significantly less in the obese and older rats than in control
      rats 12 weeks of age. Isoproterenol and a novel adrenergic beta 3-agonist,
      BRL37344, increased heat production in a concentration-dependent manner in all
      rats. The effects of isoproterenol were significantly less in the obese group
      than in the controls, while BRL37344 stimulated heat production in all rats
      almost identically. These results suggest that (1) the heat producing capacity of
      brown adipocytes is reduced by hypothalamic obesity and aging, and (2) BRL37344
      might be useful as an anti-obesity drug.

PMID- 7570687
TI  - The choice of approach in surgery for acoustic neuromas (vestibular schwannomas).
AB  - The advantages and disadvantages of the different surgical approaches for surgery
      of vestibular schwannomas are described, as well as the problems in evaluating
      the outcome of the treatment, regarding especially the evaluation of facial nerve
      function and hearing capacity. The eclectic Copenhagen treatment algorithm is
      outlined: 1) All tumors measuring 25 mm or more on MRI are operated via the
      translabyrinthine approach. 2) All patients with PTA poorer than 30 dB, and SDS
      poorer than 70% are operated via the translabyrinthine approach. 3) Tumors less
      than 10mm extrameatally, and PTA better than 30 dB and SDS better than 70% are
      removed via the middle fossa route. 4) Tumors measuring 10-25 mm and PTA better
      than 30 dB and SDS better than 70% are operated via the suboccipital route.
      Finally some consequences of postponing surgical treatment is described,
      demonstrating that 74% of 127 tumors continued to grow with a mean of 3.4 mm
      increased tumor diameter per year, and that 75% of patients, who were candidates
      for hearing preservation surgery lost the candidature in the observation period.

PMID- 7570686
TI  - Peripheral blood stem cell mobilization with chemotherapy and granulocyte-colony
      stimulating factor in patients with hematological malignancies.
AB  - Peripheral blood stem cell (PBSC) transplantation (PBSCT) following high-dose
      chemotherapy is considered to be an effective and curative strategy for patients
      with certain malignancies. Optimal conditions for collection of PBSC and
      successful PBSCT, however, are still controversial. We performed 57 leukaphereses
      after 19 courses of chemotherapy for mobilization of PBSC (semi-high-dose VP-16
      alone; 500 mg/m2/day for 3 or 4 days, 13 courses, or conventional chemotherapy;
      six courses) combined with subsequent G-CSF administration in 13 patients with
      malignancies (six with lymphoma, five with leukemia, and two with germ cell
      tumors). Total numbers of the CD34+ cells and CFU-GM obtained by multiple
      leukaphereses after one course of mobilization therapy were 0.63-168.74 x
      10(6)/kg (mean 33.94) and 0.15-56.0 x 10(5)/kg (mean 8.22), respectively. We
      demonstrated that many cellular components of peripheral blood (PB) on the day of
      PBSC harvest, especially CD34+ cell, total leukocyte, myelocyte and monocyte
      counts, were correlated with the numbers of CFU-GM obtained in each
      leukapheresis. A daily increase of leukocyte counts was another useful indicator
      for the day of PBSC harvest. We also found that the time when total leukocyte
      counts in PB recovered to more than 5000/microliters or when CD34+ cells within
      PB mononuclear cells exceeded 1% was optimal for PBSC harvest. Our results
      confirmed that the semi-high-dose regimen with VP-16 combined with G-CSF is a
      safe method which has both antitumor effects and mobilization ability of PBSC in
      patients with hematological malignancies. PBSCT following various high-dose
      chemotherapy regimens with or without total body irradiation was also performed
      in 11 of the 13 patients, and rapid hematologic recovery was observed in all of
      the patients.

PMID- 7570688
TI  - Healthcare changes bring increased liability risk for nurses.

PMID- 7570689
TI  - [The nature of the distribution and utilization of saccharose in the oral cavity
      after carbohydrate loading].
AB  - Sucrose content on surface of oral tissues and in the oral fluid following a
      carbohydrate loading was studied in vivo synchronously and over time. The content
      of sucrose adsorbed by oral tissues was assessed by its desorption with
      applications. Sucrose concentrations were the highest in the liquid closest to
      tissues in comparison with its levels in the saliva in general, this indicating a
      high cariogenic potential of the buccal mucosa due to intake of easily fermented
      carbohydrates. Prolonged utilisation of adsorbed sucrose to unavailable
      concentration provides a sufficiently long contact of mineralized tissues with
      acidogenic solutions, this promoting the development of a cariogenic situation.
      Search for means to prevent cariogenic situations should be aimed at search for
      effective desorbents of sucrose from the oral cavity just after its intake.

PMID- 7570691
TI  - [Methods for preventing periodontal diseases and their validation].
AB  - The paper presents fundamentals of comprehensive prophylaxis of periodontal
      diseases, based on the author's own epidemiological, experimental, and clinical
      findings; confirms the principal of individual differentiated complex of
      interventions as the only effective method for prevention of chronic destructive
      diseases in the periodontium.

PMID- 7570690
TI  - [A new direction in the development of Russian silver amalgams. I. The physical
      research].
AB  - A new in principle, ecologically safe and low-waste technology for preparation of
      an alloy and a formula of several silver alloys containing different levels of
      silver (OCTA-43, 70 and 80) have been developed. The absence of a alpha-2 phase
      in amalgams prepared from these alloys is their principally new feature. Physical
      properties of the new alloys were studied and compared with the known Russian and
      foreign analogs. Amalgam prepared from CCTA-43 alloy is characterized by optimal
      characteristics. By their physical characteristics the new compositions are
      superior to traditional and silver alloys manufactured in Russia at present, and
      amalgam prepared from OCTA-43 alloy is not inferior to the best foreign analogs.

PMID- 7570693
TI  - [The species composition of the dental plaque on the surface of fillings made
      from different materials].
AB  - The present research was aimed at assessment of the quantitative and qualitative
      composition of oral microflora in cases with different filling material used.
      Forty-four patients were fitted with 6 types of filling, both traditional and
      rarely used cliofil (Japan). Soft dental deposit was collected from the surface
      of fillings for microbiologic investigation. The results permit a conclusion that
      composites are preferable in comparison with amalgams and cements, the
      contamination being 8-9 times lower when they are used. Moreover, macrocomposite
      fillings were associated with streptococcal contamination, in contrast to other
      materials, when actinomycetes were mainly isolated.

PMID- 7570692
TI  - [The treatment of periodontal diseases with the preparation Linco-HAP].
AB  - Hydroxyapatite paste with lincomycin (linco-HAP) was for the time used for the
      treatment of such a prevalent disease as periodontitis. A follow-up of 380
      patients demonstrated a positive therapeutic effect of this complex expressed in
      reduction of the depth of periodontal pouches and inflammation arrest, thus
      appreciably shortening the treatment duration.

PMID- 7570695
TI  - [The effect of plasmosorption on the healing dynamics of postoperative wounds in
      patients with suppurative-inflammatory processes of the maxillofacial area and
      diabetes mellitus].
AB  - Pyoinflammatory processes run an uncommonly malignant course in diabetics.
      Healing of postoperative wounds in diabetics is caused by impairement of all
      types of metabolism and by development of endogenous intoxication which depresses
      the protein-generating function of the liver. The plasma sorption technique used
      at the clinic of Department of Maxillofacial Surgery and Dentistry, Russian State
      Medical University, helps more effectively control endogenous intoxication, this,
      in its turn, promoting activation of cleansing and healing of postoperative
      wounds. Basing on the clinical and laboratory findings, the authors demonstrated
      that plasma sorption used in multiple-modality treatment of diabetics with
      pyoinflammatory processes accelerates healing of purulent wounds by 5-6 days.

PMID- 7570694
TI  - [The use of leukinferon in treating measles in adult patients].
AB  - The following mucosal are characteristic of measles in adult patients: dryness in
      the oral cavity, dryness, desquamation, and fissures in the red edge and in the
      mouth corners, edema and hyperemia, of the buccal mucosa, macular enanthema on
      the hard and soft palate, Bel'skii-Filatov-Koplik spots, whitish deposit on the
      gingiva, edematous and bleeding gingiva, and, as a result of general
      intoxication, a lingual deposit. Leukinferon, a wide-spectrum immunocorrective
      drug, was used to improve the efficacy of treatment of adult patients with
      measles; besides alpha-interferon, it contains other cytokines of the first phase
      of immune response. Therapy with leukinferon led to a sooner improvement of the
      general status and a more rapid regression of the disease symptoms, including
      changes in the buccal mucosa, in comparison with the control leukinferon
      untreated group.

PMID- 7570699
TI  - [The pathogenesis of and treatment principles in functional overload of the
      periodontium].
AB  - A total of 4864 patients (2810 women and 2054 men) aged 16 to 64 with
      maxillofacial abnormalities and 3686 patients (2283 women and 1403 men) aged 18
      to 64 with dentition defects were examined. 2624 patients aged 19 to 62 were
      admitted for orthodontic treatment. Experiments on 96 dogs were carried out.
      Pathologic changes in the periodontal tissue were detected in 3765 (77.4%)
      patients with maxillofacial abnormalities and in 2918 (78.8%) with dentition
      defects. The author considers that two major factors contribute to the
      pathogenesis of functional overstrain of the periodontium: change of occlusion
      loading of the teeth and reduced tolerance of periodontal tissues. Good results
      were attained in 92.7% of patients with functional overloading of the
      periodontium. Dog experiments demonstrated that overexercise of teeth may lead to
      changes in the periodontium, which are similar to tissue restructuring in
      orthodontic interventions. If the periodontium is weakened, an exacerbation of
      periodontitis develops. After stopping of functional overstrain--repair processes
      in the periodontal tissues of young animals, including repair of bone tissue take
      place.

PMID- 7570698
TI  - [The role of adaptation to new medicogeographical conditions in mandibular
      fractures].
AB  - Analysis of published date and his own findings in the course of follow-up of 658
      patients with mandibular fractures, who lived under novel for them climatic and
      geographic conditions for various periods (up to 1 year, 1 to 3 years, 3 to 5
      years, permanently) brought the author to a conclusion on the contribution of
      adaptation processes to the course of healing. Some characteristics of protein
      and mineral metabolism were tested over the course of healing; for objective
      assessment, the "desirability" function was used, and indexes based on this
      function suggested: inflammatory reaction index, metabolic index, regeneration
      index. Typical changes in the pattern of metabolism and relationship between the
      incidence of complications and adaptation period were revealed. The author
      emphasizes that treatment should be planned with due consideration for the
      adaptation disorders.

PMID- 7570696
TI  - [The activity of the glutathione antioxidative system in the blood of patients
      with acute nonepidemic parotitis].
AB  - Activities of glucose-6-phosphate dehydrogenase (G-6-PDH) and malate
      dehydrogenase were measured in the blood of 38 patients with acute nonepidemic
      parotitis and the status of glutathione antioxidant system assessed. The
      predominance of free-radical processes in the mechanisms of impairment of the
      parotid gland was confirmed. Increased level of lipid peroxidation products and
      decompensation of glutathione antioxidant system were found to be due to
      incompetence of the malate shuttle and low activity of G-6-PDH. A conclusion is
      made about the necessity of revising current approaches to prevention and therapy
      of acute nonepidemic parotitis.

PMID- 7570697
TI  - [Structural changes in the periodontal tissues under measured exposure to intra-
      and extraoral orthodontic appliances in the unstable bite].
AB  - Study of the histological characteristics of the teeth, dental rudiments, and
      periodontal tissues of animals during distraction of the maxilla and distal
      dislocation of the mandible by "minor", "medium", and "strong" force showed that
      the type and degree of morphological changes are related to the strength of
      exposure and duration of orthodontist device application. The minor (1.2 H) and
      medium (2.5 H) force did not injure the studied structural elements of the
      periodical complex. Exposure of osseous tissues to a strong (5.0 H) force
      surpassing the compensatory potential of this tissue caused a complex of changes
      characterized by predominance of the processes of destruction of bone matter,
      specifically, by its resorption over its regeneration. These processes were the
      most evident during distal dislocation of the mandible. Appreciable foci of
      resorption were observed not only in the alveolar process bone, but in hard
      tissues (dentin and cement) of deciduous teeth as well. These results demonstrate
      the necessity of a careful approach to the choice of the intensity of force
      developed by various orthodontist devices.

PMID- 7570700
TI  - [The microorganism count on impression materials following disinfection by
      dynamic plasma treatment].
AB  - B. subtilis and B. cereus in concentrations under 10(5) mt, and of E. coli M-17
      below 10(7) mt on different plaster materials die within fractures of a second
      after dynamic plasma processing at atmospheric pressure and at least one passing
      of the processed surface at a rate of 2.0 to 2.5 m/s at plasma flow power of 60
      kw.

PMID- 7570701
TI  - [The late results of the conservative and surgical treatments of chronic
      periodontitis of the permanent teeth in children and adolescents].
AB  - The authors view results of conservative and surgical treatment of constant tooth
      chronic periodontitis in 90 children and adolescents aged 7-18 20 hemisections,
      45 apicoectomies, 10 radix amputations were performed. The patients were followed
      up 6 months to 5 years. X-ray films show osseous restoration on the maxilla tooth
      to complete in 5-6 months, on the mandible tooth in over 8 months. The authors
      describe indications and contraindications to such kind.

PMID- 7570702
TI  - [The clinico-laboratory diagnosis of herpetic stomatitis in newborn infants].
AB  - A clinical picture of herpetic stomatitis was studied in 173 newborns, 122 of
      these preterm and 51 full-term ones, aged 2 to 43 days. Herpesvirus origin of the
      disease was proved in 68 out of 77 examinees with stomatitis (88.31 +/- 3.66%) by
      virological and immunofluorescent methods. The authors conclude that herpetic
      stomatitis in newborns is usually a result of ante- and perinatal infection, with
      intrauterine infection occurring in 37.57 +/- 3.68% cases.

PMID- 7570704
TI  - [The function of the upper gastrointestinal tract in children with lymphangioma
      of the maxillofacial area].

PMID- 7570703
TI  - [Keratocysts of the jaws in children and adolescents with Gorlin's syndrome].
AB  - The authors review clinical and X-ray examinations of 30 patients with
      keratocysts and show difficulties of differential diagnosis with other cysts.
      Keratocysts are aggressive and prone to recurrences. The authors disclose some
      clinico-radiological, macroscopic and histological features of keratocysts which
      may be helpful in valid diagnosis making.

PMID- 7570705
TI  - [A universal approximation of the age dynamics of the main stomatological
      diseases by using the Gauss equation].
AB  - Time course of the prevalent dental diseases may be satisfactorily approximated
      by the Gauss equation, permitting a compact and universal representation of
      epidemiological date. The interpretation of equation parameters is useful from a
      theoretical and practical viewpoints.

PMID- 7570706
TI  - [The use of the laws of biomechanics and gnathology in modelling fixed dentures].

PMID- 7570707
TI  - [The basic organizational principles in the privatization of the state
      stomatological network].

PMID- 7570709
TI  - Molecular identification of steroid analogs with dissociated antiprogestin
      activities.
AB  - Antiprogestins of the 11 beta-aryl-substituted 19-norsteroid family are
      effectively used in inhibiting nidation and in terminating pregnancies. They are
      potentially useful in the treatment of progesterone-related diseases such as
      meningiomas and endometriosis and in inhibiting the growth of mammary tumors.
      However their long-term use is limited because of their inherent
      antiglucocorticoid activity. Here we have used molecular biological techniques to
      examine the antiglucocorticoid activity of a series of antiprogestins. The
      compounds we have analyzed contain different substituents at the C-17 position
      and a change from the trans to cis configuration of the C-D steroid rings. Our
      results show that minor changes at the C-17 position but not in the configuration
      of the C and D rings produced antiprogestins with reduced antiglucocorticoid
      activity. Thus only subtle changes in the structure of classical antiprogestins
      are needed for the reduction of their antiglucocorticoid activities.

PMID- 7570711
TI  - Benz[a]anthracene diols: predicted carcinogenicity and structure-estrogen
      receptor binding affinity relationships.
AB  - Benz[a]anthracenes are ubiquitous environmental carcinogens that exert estrogenic
      and antiestrogenic effects directly or via hydroxylated metabolites. In this
      paper, the structure-estrogen receptor binding relationships of four 3,9
      benz[a]anthracene diols are described: unsubstituted, 7-methyl, 12-methyl, and
      7,12-dimethyl. Compounds unsubstituted at the 12-position have flat molecular
      topology, whereas methyl substitution at the 12-position in the bay region
      induces twisting of the molecular framework. The oxygen-oxygen distances (11.94
      11.98 A) are similar to diethylstilbestrol (12.1 A). The binding affinities range
      from 0.43% to 26% that of estradiol. Methyl substitution at the 7-position
      enhances affinity; 12-methyl substitution decreases it. These results are
      contrary to many estrogen receptor (ER) ligand systems, in which the compounds
      with the flatter molecular geometries typically have lower binding affinity.
      Molecular graphics were used to analyze the fit of the four compounds with a
      receptor excluded volume model for the ER. These studies suggest that these
      compounds bind to the ER in a manner in which the anthracene fragment acts as the
      steroid AB-ring mimic (i.e, the benz[a]anthracene 9-position corresponds to the
      estradiol 3-position). Molecular orbital (AM1) calculations were used to
      calculate the charges of selected atoms. The 7-methyl compound was found to have
      greater charge similarity to estradiol than the other three compounds. The high
      affinity of the 7-methyl compound is ascribed to its charge similarity to
      estradiol, hydrophobic interactions in the receptor region that would accommodate
      a substituent in the planar 6-position of a delta 6,7-steroid, and favorable
      dispersive interactions with the receptor secondary to its extended planar
      system. Molecular orbital calculations also suggest that some of the
      benz[a]anthracene monophenols and diphenols have sufficiently low ionization
      potentials to act as carcinogens by a radical cation process.

PMID- 7570708
TI  - [An experimental study of the tissue compatibility of titanium implants coated
      with hydroxyapatite and aluminum oxide by plasma spraying].
AB  - The reaction of bone tissue to implantation of cylindric titanium implants
      sprayed with hydroxyapatite and aluminum oxide was studied. The coating was
      characterized by a high biological histocompatibility. The elements of cellular
      reactions specific for foreign bodies were absent, this permitting us to refer
      such coating to bioactive materials. The strength of fixation in the bone was
      compatible to the strength of osseous tissue adjacent to bone tissue implant. The
      coating may be used in oral implantology, traumatology, and orthodontics.

PMID- 7570710
TI  - Glucocorticoid receptor phosphorylation in v-mos-transformed cells.
AB  - Nucleocytoplasmic shuttling of glucocorticoid receptors (GRs) is disrupted in v
      mos-transformed cells leading to the redistribution of hormone-bound receptors
      from the nuclear to cytoplasmic compartments. We show here that GRs from v-mos
      transformed cells are hyperphosphorylated on a specific peptide and maintain
      hormone-induced phosphorylations upon a prolonged hormone treatment that is
      associated with disruptions in its nucleocytoplasmic shuttling. Since similar
      effects on GR nucleocytoplasmic shuttling and phosphorylation were exerted upon
      treatment of nontransformed cells with the protein phosphatase inhibitor okadaic
      acid, we examined whether hyperphosphorylation of GRs in v-mos-transformed cells
      resulted from inhibition of receptor dephosphorylation. Protein phosphatase
      activity, measured using various substrates in vitro, was identical in cell-free
      extracts prepared from v-mos-transformed and nontransformed cells. Analysis of
      phosphate turnover in vivo from either the sum of all GR phosphorylation sites or
      from individual sites using pulse-chase analysis, did not reveal any significant
      difference between v-mos-transformed cells versus nontransformed cells. Thus,
      hyperphosphorylation of GR in v-mos-transformed cells does not appear to result
      from inhibition of GR dephosphorylation, but rather from stimulation of GR
      phosphorylation.

PMID- 7570713
TI  - Activity of ecdysone analogs in enhancing N-acetylglucosamine incorporation into
      the cultured integument of Chilo suppressalis.
AB  - Ecdysone analogs with various side chains at the 17-position of the steroid
      structure enhanced the incorporation of N-acetylglucosamine as 20-hydroxyecdysone
      into the cultured integument prepared from Chilo suppressalis. Their activity in
      terms of the concentration required to give 50% of the maximum response varied
      with the structure. Piperonyl butoxide, an inhibitor of oxidation metabolism, did
      not enhance the in vitro effect of the compounds. The order of potency was
      ponasterone A > 20-hydroxyecdysone > cyasterone > inokosterone > makisterone A >>
      ecdysone.

PMID- 7570714
TI  - Bidirectional activity of 11 beta-hydroxysteroid dehydrogenase in vascular smooth
      muscle cells.
AB  - Endogenous glucocorticoids (GC) can be metabolized through the enzyme 11 beta
      hydroxysteroid dehydrogenase (11 beta-OHSD); in the rat, corticosterone (B) is
      converted to its inactive metabolite 11-dehydrocorticosterone (A). Since
      increased tissue concentrations of GCs may affect blood pressure by potentiating
      the vasoactive effects of alpha-adrenergic agonists and possibly other pressors,
      we studied the metabolism of corticosterone in freshly dissected aortae and
      cultured vascular smooth muscle cells (VSMC). Incubations were generally
      conducted for 60 min with 10(-8) M steroid; steroids were isolated and identified
      by HPLC. In aortic minces stripped of endothelium, the oxo-reductase reaction of
      A back to B was nearly 4 times greater than the dehydrogenase reaction of B to A
      (2.8 +/- 0.5 x 10(-11) versus 7.3 +/- 1.0 x 10(-12) mol/mg protein). This pattern
      was also seen in cultured VSMC during growth and quiescent states (growth A to B
      3.2 +/- 0.4 x 10(-12) versus B to A 9.7 +/- 0.9 x 10(-13) mol/mg protein;
      quiescent A to B 8.8 +/- 0.1 x 10(-12) versus B to A 1.2 +/- 0.2 x 10(-12) mol/mg
      protein). Enzyme activity in either direction was less during growth, correlating
      with a decrease in mRNA for 11 beta-OHSD. In cell homogenates containing 200
      microM NADP(H), the enzyme functioned equally in either direction at pH 7.4 with
      an apparent Km for corticosterone of approximately 2 x 10(-7) M. Carbenoxolone,
      an inhibitor of 11 beta-OHSD, suppressed the dehydrogenase reaction to a greater
      degree than the reverse oxo-reductase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570712
TI  - Effect of phospholipids and organic solvents on the formation of 5,16
      androstadien-3 beta-ol from pregnenolone in adrenal and testicular microsomes.
AB  - The formation of 5,16-androstadien-3 beta-ol from pregnenolone (andien-beta
      synthase activity) is catalyzed by cytochrome P450c17, which also catalyzes C-17
      hydroxy/lyase activity in the biosynthesis of androgens. Andien-beta synthase is
      very active in porcine Leydig cells, but it is almost undetectable in porcine and
      bovine adrenal, although the adrenal gland also expresses P450c17. We have
      treated microsomal preparations with lipids and organic solvents to examine if
      the andien-beta synthase and C-17-hydroxy/lyase activities of P450c17 were
      affected by these agents. The addition of some phospholipids to the microsomal
      preparations inhibited both P450c17 activities. Phospholipids with different
      fatty acids had no effect on the ratio of andien-beta synthase to C-17
      hydroxy/lyase activity. The addition of solvents to the microsomal preparations
      generally inhibited both P450c17 activities. However, the addition of acetyl
      acetone up to 5% (v/v) preferentially increased the andien-beta synthase activity
      while decreasing, the C-17-hydroxy/lyase activity. The effect was dose-dependent,
      specific to acetyl acetone and was seen in both testis and adrenal microsomes.
      The exact nature of the stimulation of andien-beta synthase activity is unknown,
      but the andien-beta synthase activity obtained after treatment with acetyl
      acetone was directly correlated to total P450c17 activity in the untreated
      microsomes. The inhibition of C-17-hydroxy/lyase activity by acetyl acetone was
      particularly apparent with the C-17,20-lyase reaction rather than the 17 alpha
      hydroxylase reaction. The addition of acetyl acetone can potentially be used to
      assess the total potential of P450c17 to catalyze andien-beta synthase activity
      in vitro.

PMID- 7570716
TI  - Synthesis of C-6 fluoroandrogens: evaluation of ligands for tumor receptor
      imaging.
AB  - Seven androgens, substituted with fluorine at C-6, were prepared as potential
      imaging agents for androgen receptor-positive prostate tumors and were evaluated
      in vitro in terms of their lipophilicity and their relative binding affinities
      (RBA, relative to R 1881 = 100) for the androgen receptor and for sex steroid
      binding protein. Introduction of a fluorine atom into the C-6 position of an
      androgen generally decreases binding affinity to the androgen receptor, except in
      the two cases: 6 alpha-fluoro-19-nor-testosterone (RBA = 41.6 versus 30.6 for the
      unsubstituted steroid) and 6 alpha-fluorotestosterone (RBA = 8.9 versus 6.6).
      Receptor binding of the C-6 fluoro-androgens is also stereospecific, showing
      higher binding affinities for the alpha-epimers compared to the corresponding
      beta-epimers (4:1-15:1). Binding affinity to sex steroid binding protein is the
      lowest with 19-nor-testosterone, which is also the least lipophilic androgen
      studied. Based on the binding properties of compounds in this series, 6 alpha
      fluoro-19-nor-testosterone appears to have the most promise as a tumor imaging
      agent.

PMID- 7570715
TI  - A simple synthesis of 11,19-oxidosteroids.
AB  - The photochemical hypoiodination of cortisol acetonide gave a mixture of 18
      iodocortisol acetonide and of the 11 beta,19-oxidoderivative. The proportion of
      the two products was slightly modified by the reaction temperature. Deprotection
      of the acetonide group of the 11 beta,19-oxidoderivative gave 11 beta,19-oxido-17
      alpha,21-dihydroxy-4-pregnen-3,20-dione which led to the formation of 11 beta,19
      oxido-4-androsten-3,17-dione upon treatment with sodium bismutate.

PMID- 7570717
TI  - Aromatase inhibitors: effect of ring A and ring B unsaturation on aromatase
      inhibition by 4-thiosubstituted derivatives of 4-androstene-3,17-dione.
AB  - The synthesis and biological evaluation of 4-thiosubstituted derivatives of 1,4
      androstadienedione, 4,6-androstadienedione, and 1,4,6-androstatrienedione as
      inhibitors of aromatase are described. Inhibitory activity of synthesized
      compounds was assessed using a human placental microsomal preparation as the
      enzyme source and [1 beta-3H]androstenedione as substrate. Under initial velocity
      assay conditions of low product formation, the inhibitors demonstrated potent
      inhibition of aromatase, with apparent Kis ranging from 9.8 to 137 nM and with Km
      for androstenedione being 38 nM. However, unlike other 1,4-androstadienediones
      and 1,4,6-androstatrienediones in which time-dependent inactivation was observed,
      the 4-thiosubstituted analogs were found to be competitive inhibitors and did not
      produce any time-dependent inactivation of aromatase.

PMID- 7570718
TI  - Skepticism toward carotid ultrasonography. A virtue, an attitude, or fanaticism?

PMID- 7570719
TI  - Accuracy and prognostic consequences of ultrasonography in identifying severe
      carotid artery stenosis. North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) Group.
AB  - BACKGROUND AND PURPOSE: The accuracy of routine ultrasonography in detecting
      severe carotid artery stenosis was evaluated in comparison with cerebral
      angiography. The precision of ultrasonographic criteria in predicting the risk of
      stroke was also assessed. METHODS: A total of 1011 symptomatic carotid
      bifurcations were studied in patients from the North American Symptomatic Carotid
      Endarterectomy Trial (NASCET). Given that all patients were considered for entry
      into the trial, the chance of a verification bias affecting the analyses was
      minimized. The ultrasonographic data consisted of peak systolic velocities and
      frequency changes from both the internal and common carotid arteries.
      Angiographic stenosis was calculated as in NASCET. Receiver operating
      characteristic (ROC) curves were constructed from the ultrasonographic data for
      the detection of 70% or greater stenosis on the basis of an angiographic
      assessment. Kaplan-Meier stroke-free survival curves were used to predict the
      risk of stroke. RESULTS: The areas under the ROC curves ranged from 0.74 to 0.75
      (95% confidence interval [CI], 0.69 to 0.79). The sensitivities and specificities
      ranged from 0.65 to 0.71. The risk of stroke at 18 months declined sharply as the
      degree of angiographically defined stenosis declined from 99% to 70%. No pattern
      of decline was apparent on the basis of the ultrasonographic data. CONCLUSIONS:
      The results indicate that the accuracy of ultrasonography is moderate when flow
      parameters are used to assess the degree of stenosis. Ultrasonography should be
      used as a screening tool to exclude patients with no carotid artery disease from
      further testing. Conventional angiography remains an essential investigation
      before assigning the risk of stroke and deciding appropriate treatment for
      extracranial carotid artery disease.

PMID- 7570720
TI  - Preoperative assessment of the carotid bifurcation. Can magnetic resonance
      angiography and duplex ultrasonography replace contrast arteriography?
AB  - BACKGROUND AND PURPOSE: Noninvasive studies are used with increasing frequency to
      assess the carotid bifurcation before endarterectomy. Therefore, assessment of
      their diagnostic accuracies is essential for appropriate patient management. We
      prospectively evaluate two noninvasive tests, magnetic resonance angiography
      (MRA) and duplex ultrasonography (DU), as potential replacements for contrast
      arteriography (CA). METHODS: A blinded comparison of three-dimensional time-of
      flight (TOF) MRA, two-dimensional TOF MRA, and DU in 176 arteries was performed.
      CA was used as the standard of comparison. RESULTS: Three-dimensional TOF MRA had
      a sensitivity of 94%, a specificity of 85%, and an accuracy of 88% for the
      identification of 70% to 99% stenosis; two-dimensional TOF MRA had a sensitivity
      and specificity that were approximately 10% lower than those of three-dimensional
      TOF MRA. DU resulted in a sensitivity of 94%, a specificity of 83%, and an
      accuracy of 86%. Combining data from three-dimensional TOF MRA and DU, allowing
      for CA only for disparate results, yielded a sensitivity of 100%, a specificity
      of 91%, and an accuracy of 94% among concordant noninvasive tests, with CA
      required in 16% of arteries. MRA accurately differentiated 17 carotid occlusions
      from 16 high-grade (90% to 99%) stenoses, whereas with DU two patent arteries
      were identified as occluded and one occluded artery was identified as patent.
      CONCLUSIONS: Three-dimensional TOF MRA is the most accurate noninvasive test.
      Combined use of MRA and DU results in a marked increase in accuracy to a level
      that obviates the need for CA in a majority of patients.

PMID- 7570721
TI  - Role of social class in excess black stroke mortality.
AB  - BACKGROUND AND PURPOSE: It has been suggested that a substantial proportion of
      the excess stroke mortality among black Americans may be attributable to
      relatively lower socioeconomic status (SES) in this group. In this report we
      provide the first quantitative estimates of the proportion of excess black stroke
      mortality attributable to SES for a large population-based cohort. METHODS: We
      used data from the National Longitudinal Mortality Study for persons 45 years and
      older (73,400 white men, 87,528 white women, 6522 black men, and 8816 black
      women). Sex-specific proportional hazards model were used to estimate excess
      black stroke mortality with and without adjustment for education and income
      (measures of SES). The contribution of SES to the excess black stroke risk was
      estimated from the difference in regression coefficients for race in these
      models. RESULTS: In men, low SES was associated with increased stroke mortality
      (P < or = .0001) and accounted for 14% to 46% of the excess black stroke risk (P
      < .05). However, we could find no association between SES and stroke mortality in
      women, and SES did not account for a significant proportion of the excess stroke
      mortality in black women. CONCLUSIONS: Although SES proved to account for a
      statistically significant proportion of excess male black stroke mortality,
      overall SES explained less than one quarter of the observed excess between ages
      45 and 65. In women, SES did not significantly reduce the estimated excess black
      stroke mortality. Although SES may be playing a role in excess black stroke
      mortality, a substantial proportion of the excess appears attributable to other
      sources, including cerebrovascular risk factors that are unrelated to SES,
      unmeasured lifestyle influences, social resources, and genetic factors.

PMID- 7570723
TI  - Alcohol consumption and stroke mortality. 20-year follow-up of 15,077 men and
      women.
AB  - BACKGROUND AND PURPOSE: Since stroke is a principal cause of death in elderly
      people, we analyzed the association between alcohol and stroke mortality in a
      cohort of 15,077 middle-aged and older men and women. METHODS: Data on alcohol
      habits were obtained from a questionnaire in 1967. The subsequent 20 years
      yielded 769 deaths from stroke, of which 574 were ischemic. Relative mortality
      risks (RR) were estimated from logistic regression analyses with lifelong alcohol
      abstainers as a reference group. Adjustments were made for age and smoking.
      RESULTS: No association was found between alcohol intake and hemorrhagic stroke.
      An elevated risk of ischemic stroke was found for men who drank infrequently,
      that is, a few times a year or less often (RR, 2.0; 95% confidence interval [CI],
      1.3 to 3.2), for those who were intoxicated now and then (RR, 1.8; 95% CI, 1.1 to
      2.8), and for those who reported "binge" drinking a few times in the year or less
      often (RR, 1.6; 95% CI, 1.1 to 2.5). Among women only ex-drinkers had an elevated
      risk of dying of ischemic stroke (RR, 3.3; 95% CI, 1.5 to 7.2). The risk was
      reduced for women who had an estimated average consumption of 0 to 5 g pure
      alcohol per day (RR, 0.6; 95% CI, 0.5 to 0.8); for those who did not drink every
      day (RR, 0.7; 95% CI, 0.5 to 0.9); and for those who never "went on a binge" (RR,
      0.6; 95% CI, 0.5 to 0.8) or became intoxicated (RR, 0.7; 95% CI, 0.5 to 0.9).
      CONCLUSIONS: Drinking habits were associated only with deaths from ischemic
      stroke, and the risk patterns were different for men and women. In analyses, ex
      drinkers should not be included with lifelong abstainers, since the former tend
      to run high health risk.

PMID- 7570722
TI  - Predictors of early deterioration and mortality in black Americans with
      spontaneous intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Black Americans with spontaneous intracerebral hemorrhage
      (SICH) may have unique clinical characteristics that affect outcome. The aim of
      this study was to determine the prognostic value of clinical characteristics and
      initial CT scan for outcome in black Americans with SICH. METHODS: Clinical and
      demographic data were extracted from the charts of 182 consecutive black
      Americans admitted for SICH diagnosed by clinical criteria and initial CT scan.
      Hemorrhage volumes were calculated from admission CT scans by a computerized
      method. Univariate and multiple logistic regression analyses were performed to
      determine independent predictors of early deterioration (defined as a decrease
      from an initial Glasgow Coma Scale score > 12 by > or = 4 points within 24 hours
      from presentation) and mortality. RESULTS: Both hemorrhage volume and ventricular
      extension were significant, independent predictors of early deterioration (odds
      ratio [OR], 6.78; 95% confidence interval [CI], 1.89 to 24.35 and OR, 4.67; 95%
      CI, 1.30 to 16.72, respectively) and mortality (OR, 6.66; 95% CI, 2.85 to 15.58
      and OR, 4.23; 95% CI, 1.82 to 9.82, respectively). A Glasgow Coma Scale score <
      or = 12 also predicted mortality (OR, 3.23; 95% CI, 1.46 to 7.14). Initial mean
      arterial pressure was not an independent predictor of early deterioration or
      mortality. CONCLUSIONS: Hemorrhage volume and ventricular extension are the best
      predictors of early deterioration and mortality in black Americans with SICH.

PMID- 7570724
TI  - Changes in the sex ratio of stroke mortality in the period of 1955 through 1990.
AB  - BACKGROUND AND PURPOSE: Stroke mortality worldwide has decreased in men and women
      in most industrialized countries, except in eastern European countries. The
      purpose of this study was to compare the sex ratio of stroke mortality between
      populations and over time. This approach may help to determine the factors
      influencing this ratio. METHODS: The sex ratios (men to women) of stroke
      mortality between ages 55 to 64, 65 to 74, and 75 to 84 years from 27 populations
      between 1955 and the latest available year were analyzed using World Health
      Organization data. The relationship between log stroke mortality and age and the
      relationships between alcohol, animal fat, cigarette consumption, and urinary
      cation excretion and the sex ratio of stroke mortality were also analyzed.
      RESULTS: The mean sex ratio of stroke mortality increased 50%, 34%, and 15% in
      the three age classes, respectively, over 35 years. Highly significant
      relationships of log stroke mortality with age exist, which vary between men and
      women and among countries. In general, stroke mortality changed in the same
      direction in both sexes but decreased earlier and more rapidly in women than in
      men. Alcohol consumption and urinary sodium excretion correlated positively and
      significantly with the sex ratio. The time trends of the sex ratio also
      correlated positively and significantly with the time trends of cigarette
      consumption. No relationship with animal fat consumption was found. CONCLUSIONS:
      The sex ratio of stroke mortality is increasing with time and decreasing with
      age. Differences in lifestyle among countries and over the last three decades may
      contribute partially to these differences in sex ratio.

PMID- 7570725
TI  - Ischemic stroke events and carotid atherosclerosis. Results of the Osaka Follow
      up Study for Ultrasonographic Assessment of Carotid Atherosclerosis (the OSACA
      Study).
AB  - BACKGROUND AND PURPOSE: To clarify the clinical significance of carotid
      atherosclerosis for ischemic stroke events, a follow-up study was performed in
      Japanese patients. METHODS: Two hundred fourteen patients were registered from
      nine hospitals in the Osaka community. All patients were checked for a prior
      history of stroke, and the risk factors for stroke and atherosclerosis were
      evaluated. Carotid atherosclerosis was assessed by 7.5-MHz duplex
      ultrasonography. We studied the relationship between the ischemic stroke event
      rate and the severity and appearance of the carotid atherosclerosis. We also
      studied the relationship between stroke events and various risk factors. RESULTS:
      The average duration of follow-up was 16 months. Ten patients suffered new
      ischemic stroke episodes during this follow-up period. At the initial
      ultrasonographic study, 16 patients had high-grade stenosis and 21 had ulcerated
      plaque. Proportional hazard regression analysis showed that grade of stenosis and
      plaque ulceration were positively related to the event rate. Patients with
      ulcerated plaque had a sevenfold higher hazard ratio for stroke in comparison to
      those without (P < .01). The ipsilateral stroke recurrence rate was 11 times
      higher in patients with ulcerated high-grade stenotic carotid lesions.
      CONCLUSIONS: The present findings demonstrate that the severity of carotid
      atherosclerosis as evaluated by ultrasonography is a useful indicator of the risk
      of ischemic stroke in symptomatic patients.

PMID- 7570726
TI  - Incidence and prognosis of stroke in the Belluno province, Italy. First-year
      results of a community-based study.
AB  - BACKGROUND AND PURPOSE: We sought to register the incidence rate, risk factors,
      and case-fatality rate of all the new cases of first-ever-in-a-lifetime stroke in
      the province of Beluno, Italy. This study aimed to provide an epidemiological
      survey of cerebrovascular disease that could supply investigative objectives and
      support information for regional healthcare facilities planning. METHODS: We
      undertook a prospective population-based study in the territory of the 1st, 2nd,
      3rd, and 4th local health units in the province of Belluno, an area located in
      northeast Italy (population, 211 389). RESULTS: In the first year of the study
      (June 1, 1992, to May 31, 1993), 474 cases of first-ever stroke were registered.
      The crude annual incidence rate was 2.24/1000 (2.01/1000 for men and 2.45/1000
      for women). After adjustment to the European population, the incidence rate for
      first stroke was 1.70/1000 per year. The pathological diagnosis was confirmed by
      a CT scan in 89.5% of cases. Cerebral infarction accounted for 319 cases, while
      93 patients suffered a primary intracerebral hemorrhage, 12 patients a
      subarachnoid hemorrhage, and 50 patients a stroke of unknown origin. The overall
      30-day case-fatality rate was 33%, and the mortality within the first week from
      stroke onset was 23%. The recurrence rate after 1 month was 1.9%. After 1 month,
      46% of our patients were functionally independent in activities of daily living.
      CONCLUSIONS: Our first-year results confirm the fairly high risk for stroke in
      central and northern Italy and support European findings regarding risk factors
      for stroke.

PMID- 7570727
TI  - Simultaneous cerebrovascular and cardiovascular responses during presyncope.
AB  - BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs
      indicative of imminent syncope, can be aborted in many situations before loss of
      consciousness occurs. The plasticity of cerebral autoregulation in healthy humans
      and its behavior during this syncopal prodrome are unclear, although systemic
      hemodynamic instability has been suggested as a key factor in the precipitation
      of syncope. Using lower body negative pressure (LBNP) to simulate central
      hypovolemia, we previously observed falling mean flow velocities (MFVs) with
      maintained mean arterial blood pressure (MABP). These findings, and recent
      reports suggesting increased vascular tone within the cerebral vasculature at
      presyncope, cannot be explained by the classic static cerebral autoregulation
      curve; neither can they be totally explained by a recent suggestion of a
      rightward shift in this curve. METHODS: Four male and five female healthy
      volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and
      cardiovascular responses by use of continuous acquisition of MFV from the right
      middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and
      heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14%
      of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its
      baseline level. Estimated cerebrovascular resistance increased during LBNP. The
      percentage change from baseline to presyncope in MFV and MABP revealed consistent
      decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular
      resistance, falling MFV, and constant MABP are evidence of an increase in
      cerebral vascular tone with falling flow, suggesting a downward shift in the
      cerebral autoregulation curve. Cerebral vessels may have a differential
      sensitivity to sympathetic drive or more than one type of sympathetic
      innervation. Future work to induce dynamic changes in MABP during LBNP may help
      in assessing the plasticity of the cerebral autoregulation mechanism.

PMID- 7570729
TI  - Is blood pressure really a trigger for the circadian rhythm of subarachnoid
      hemorrhage?
AB  - BACKGROUND AND PURPOSE: Circadian blood pressure changes are not infrequently
      cited as a trigger for the onset of subarachnoid hemorrhage (SAH). Our purpose
      was to determine the reliability of this chronorisk and study the variability and
      consequences of it as it occurs in hypertensive and normotensive individuals.
      METHODS: Of 273 consecutive patients with proven SAH of aneurysmal origin seen
      between January 1990 and December 1993, we studied 120 (44%) for whom the exact
      time of hemorrhage could be reliably determined. Beyond the recognition of a
      circadian rhythm for this collective, the patients were then sorted by blood
      pressure, yielding one group each of 80 normotensive (group N, 66.7%) and
      hypertensive (group H, 33.3%) individuals. The differential chronorisk of these
      two groups was studied. RESULTS: A circadian rhythm with a definitive
      characteristic acrophase was observed for the entire group, occurring between 9
      AM and 10 AM (chi 2 test, P < .0005) with a possible secondary peak in the
      afternoon hours. The separation into two blood pressure groups somewhat
      surprisingly revealed a different curve for each group (chi 2 test, P = .01).
      Statistical analysis of each group's separate chronorisk revealed that this
      acrophase only holds true for hypertensive individuals, whereas normotensive
      patients not only lack a morning peak, but an apparent elevation in the afternoon
      is statistically irrelevant, leading to the impression that SAH in normotensive
      persons seems to be subject to no circadian rhythm at all. CONCLUSIONS: The
      incidence of SAH conforms to circadian blood pressure variation in hypertensive
      patients, similar to the diurnal rhythms observed with strokes and myocardial
      infarctions. This leads to the hypothesis that blood pressure elevation is a
      trigger for the onset of bleeding in this group. In clear contrast, normotensive
      individuals with cerebrovascular aneurysms seem to have a random 24-hour
      distribution of SAH onset times, thus leaving the nature of a possible trigger
      mechanism unresolved.

PMID- 7570730
TI  - Postprandial and orthostatic cardiovascular changes after acute stroke.
AB  - BACKGROUND AND PURPOSE: Large falls in blood pressure after meals have been
      demonstrated in fit and frail elderly subjects; these changes may be associated
      with an increased incidence of stroke. Postprandial falls in BP may be
      particularly deleterious after acute stroke, when normal baroreflex mechanisms
      and cerebral autoregulation are already impaired, resulting in stroke
      progression. Therefore, the postprandial hemodynamic responses to orthostasis
      were examined in nine acute stroke subjects and eight age-, sex-, and blood
      pressure-matched control subjects after an oral energy load. METHODS: All
      subjects were studied on two occasions in a randomized, double-blind, crossover
      trial after administration of either oral glucose (1 g/kg body wt) or equivalent
      isovolumic, isosmotic xylose (0.83 g/kg). Measurements of blood pressure, pulse
      rate, and forearm blood flow were recorded for 30 minutes preprandially and 90
      minutes postprandially. Hemodynamic responses to 60 degrees tilt, along with
      plasma glucose and insulin changes, were measured at baseline and at 30-minute
      intervals postprandially. RESULTS: Supine mean arterial and diastolic blood
      pressures fell significantly after glucose but not xylose ingestion in control
      subjects (P < .03) but not stroke subjects, whereas supine pulse rate increased
      in stroke subjects (P < .04) only. No significant changes in forearm vascular
      resistance were recorded in either control or stroke subjects. After tilt, stroke
      subjects showed a fall in mean arterial pressure compared with control subjects
      preprandially (P = .03) and at 30 (P < .005) and 90 (P < .03) minutes
      postprandially, although no differences were observed between the xylose and
      glucose phases. Orthostatic tolerance was maintained in control subjects
      throughout both phases of the study. Pulse rate increased significantly to tilt
      at all time intervals in both groups, although there were no significant changes
      in forearm vascular resistance. CONCLUSIONS: Acute stroke subjects are not at
      significantly greater risk of blood pressure falls in response to an oral energy
      load than age-, sex-, and blood pressure-matched control subjects. Unlike control
      subjects, the stroke group had an increased pulse-rate postprandially, which
      could result in a compensatory rise in cardiac output as a result of increased
      sympathetic nervous system activity in the poststroke period. Although
      orthostatic blood pressure control is impaired after acute stroke, these changes
      are unaffected by meals.

PMID- 7570731
TI  - Photoreactive flow changes in the posterior cerebral artery in control subjects
      and patients with occipital lobe infarction.
AB  - BACKGROUND AND PURPOSE: Photoreactive flow changes of the posterior cerebral
      artery (PCA) in control subjects and patients with unilateral occipital lobe
      infarction were investigated to study the hypothesis that occipital lobe
      infarction of varying extent leads to a reduced visually activated flow increase
      in the ipsilateral PCA. METHODS: Maximum mean flow velocity (MFV) of the PCA was
      investigated by transcranial Doppler sonography after photic stimulation of the
      retina. RESULTS: In 25 control subjects MFV was increased by 30.6 +/- 9.7%. In 13
      patients with unilateral occipital lobe infarction the ipsilateral MFV increase
      was significantly lower than in control subjects. Nine patients with homonymous
      hemianopsia showed an ipsilateral MFV increase of 3.4 +/- 4.1% (P < .001) and
      four patients with incomplete occipital lobe infarction and homonymous
      quadrantanopsia had an MFV increase of 16.0 +/- 12.8% (P < .05). CONCLUSIONS: We
      conclude that photoreactive flow changes of the PCA represent a noninvasive and
      reliable measure of functional impairment due to occipital infarction.

PMID- 7570728
TI  - Phase relationship between cerebral blood flow velocity and blood pressure. A
      clinical test of autoregulation.
AB  - BACKGROUND AND PURPOSE: This study investigates the usefulness, as a test of
      dynamic autoregulation, of phase shift angle analysis between oscillations in
      cerebral blood flow velocity (CBFV) and in arterial blood pressure (ABP) during
      deep breathing. METHODS: Fifty healthy volunteers, 20 patients with occlusive
      cerebrovascular diseases (OCD), and 10 patients with arteriovenous malformations
      (AVM) took part in the study. All subjects received transcranial Doppler
      monitoring of both middle cerebral arteries (MCAs). In addition, continuous blood
      pressure monitoring was performed with the use of noninvasive servo-controlled
      infrared finger plethysmography during deep breathing at a rate of 6/min. With
      the use of a high-pass filter model of autoregulation, autoregulation was
      quantified as phase shift angle between oscillations in CBFV and ABP at a
      frequency of 6/min. A phase shift angle of 0 degrees indicates total absence of
      autoregulation, while 90 degrees can be gauged as optimal autoregulation. In
      addition, vasomotor reactivity of both MCAs to CO2 stimulation was assessed among
      patients and calculated as percent increase in CBFV per millimeter of mercury of
      increase in CO2. RESULTS: All normal subjects showed positive phase shift angles
      between CBFV and ABP (mean +/- SD, 70.5 +/- 29.8 degrees). OCD patients presented
      with significantly decreased phase shift angles for the MCA only on the
      pathological side (51.7 +/- 35.1 degrees; P < .05). Patients with AVM showed
      significantly reduced phase shift angles on both the affected side (26.8 +/- 13.5
      degrees; P < .001) and the unaffected side (40.6 +/- 26.6 degrees; P < .01). In
      patients' groups, phase shift angle and vasomotor reactivity correlated
      significantly (r = .66; P < .001) after results from all MCAs were pooled.
      CONCLUSIONS: Results confirm the high-pass filter model of cerebral
      autoregulation: Normal subjects showed predicted positive phase shift angles
      between CBFV and ABP oscillations. Patients with expected autoregulatory
      disturbances showed significant decreases in phase shift angles. Close
      correlations existed between autoregulation and CO2-induced vasomotor reactivity.

PMID- 7570732
TI  - Selection of patients for transesophageal echocardiography after stroke and
      systemic embolic events. Role of transthoracic echocardiography.
AB  - BACKGROUND AND PURPOSE: This study examined whether patients suffering from
      stroke and other systemic embolic events may be selected for transesophageal
      echocardiography on the basis of clinical and transthoracic echocardiographic
      findings. METHODS: We performed transthoracic and transesophageal
      echocardiography on 824 patients after stroke and other suspected embolic events.
      Patients were classified into group A if they were in sinus rhythm and had a
      normal transthoracic echocardiogram. Group B consisted of all other patients.
      Transesophageal echocardiographic findings of left atrial spontaneous contrast,
      left atrial thrombus, complex aortic atheroma, and interatrial septal anomalies
      were correlated with clinical and transthoracic echocardiographic results.
      RESULTS: Transesophageal echocardiography detected at least one potential source
      of embolism in 399 patients (49%): spontaneous contrast in 214 patients (26%),
      left atrial thrombus in 54 (7%), complex atheroma in 111 (13%), and interatrial
      septal anomalies in 126 (15%). In group A (n = 236), only 3 (1%) had spontaneous
      contrast, 11 (4.6%) had complex atheroma, and none had left atrial thrombus. In
      group B (n = 588), 211 patients (36%, P < .001) had spontaneous contrast, 54
      (9.2%, P < .001) had atrial thrombus, and 100 (17%, P < .001) had complex
      atheroma. Interatrial septal anomalies were detected in similar proportions of
      patients (18% in group A versus 14% in group B). Left atrial spontaneous echo
      contrast, thrombus, and complex atheroma were significantly more prevalent in
      older patients, but interatrial septal anomalies were more prevalent in younger
      patients irrespective of transthoracic echocardiographic findings. Multivariate
      analysis identified both an abnormal transthoracic echocardiogram and patient age
      to be independent predictors of transesophageal echocardiographic findings of
      left atrial spontaneous echo contrast, left atrial thrombus, or complex atheroma.
      CONCLUSIONS: Transesophageal echocardiography has a low yield for left atrial
      spontaneous contrast, left atrial thrombus, or complex aortic atheroma in
      patients with normal transthoracic echocardiogram and sinus rhythm and in younger
      patients. Interatrial septal anomalies are more prevalent in younger patients.
      Transthoracic echocardiogram should be performed in patients after stroke or
      systemic embolic events as a noninvasive screening tool. We recommend
      transesophageal echocardiogram for patients with abnormal transthoracic
      echocardiogram and in younger patients when the finding of a patent foramen ovale
      may contribute to patient management.

PMID- 7570734
TI  - Costs of medical care after first-ever stroke in The Netherlands.
AB  - BACKGROUND AND PURPOSE: Stroke causes high morbidity and mortality. The aging of
      the population further increases the demands on healthcare costs. METHODS: We
      estimated the lifetime direct costs of care of first-ever stroke patients in the
      Netherlands in 1991 using epidemiological data from national and international
      studies. In addition, we examined the effect of an aging population on future
      healthcare costs. RESULTS: The lifetime costs for 24,007 first-ever stroke
      patients are estimated to be 1870 million Dutch guilders (Dfl) (1 Dfl = 0.53 US
      dollar, 1991). Per-person costs are higher for women (83,000 Dfl) than for men
      (71,000 Dfl). The major cost component of first-year costs is hospital costs
      (45%), while nursing home costs dominate lifetime costs (50%). An increase of the
      elderly population older than 65 years of 27% between 1991 and 2010 might lead to
      a parallel increase of total costs of 30%, or 1.5% per year. CONCLUSIONS: Long
      term care rather than acute care dominates the lifetime costs for stroke patients
      now and in the future.

PMID- 7570733
TI  - Time dependency of the acetazolamide effect on cerebral hemodynamics in patients
      with chronic occlusive cerebral arteries. Early steal phenomenon demonstrated by
      [15O]H2O positron emission tomography.
AB  - BACKGROUND AND PURPOSE: The acetazolamide effect is thought to reach a maximum at
      10 to 20 minutes after administration. However, we sometimes encountered patients
      who showed a transient deterioration of ischemic symptoms several minutes after
      acetazolamide administration. We therefore considered that a steal phenomenon may
      occur before the acetazolamide effect reaches a maximum. We evaluated the time
      dependency of the acetazolamide effect on cerebral hemodynamics in patients with
      severe stenosis or occlusion of the unilateral internal carotid artery. METHODS:
      The subjects consisted of 13 patients with severe stenosis or occlusion of the
      unilateral internal carotid artery. Regional cerebral blood flow was measured at
      the resting state and at 5 and 20 minutes after the intravenous administration of
      1 g acetazolamide by the use of the [15O]H2O bolus-injection method and positron
      emission tomography. The steal phenomenon was interpreted as positive when the
      regional cerebral blood flow values decreased by more than 10% after the
      administration of acetazolamide in more than one region of interest. RESULTS: A
      steal phenomenon was observed in 5 of 13 patients at 5 minutes after
      acetazolamide administration on the occlusive side, whereas it was observed in
      only 1 patient at 20 minutes. Thus, this phenomenon was observed more frequently
      in the early phase of the acetazolamide test. It was also observed more
      frequently in patients with poorly developed collateral circulation. CONCLUSIONS:
      Our acetazolamide [15O]H2O positron emission tomography study revealed an early
      steal phenomenon at 5 minutes after intravenous administration of acetazolamide,
      which may be a cause of the transient deterioration of ischemic symptoms during
      the acetazolamide test.

PMID- 7570735
TI  - Clinical and prognostic correlates of stroke subtype misdiagnosis within 12 hours
      from onset.
AB  - BACKGROUND AND PURPOSE: Pure motor hemiparesis and sensorimotor stroke syndromes
      are not accurate predictors of lacunar infarct when described in the first 12
      hours of stroke onset. We evaluate here whether this inaccuracy of clinical
      diagnosis might have influenced the planning of patient management either in
      routine practice or in therapeutic trials. METHODS: A consecutive hospital series
      of 517 first-ever ischemic hemispheric stroke patients presented lacunar or
      nonlacunar syndromes at the first examination within 12 hours of the event. A
      distinction was subsequently made, by means of a CT scan or autopsy performed
      within 15 +/- 2 days of stroke, between patients affected by lacunar or
      nonlacunar infarcts. We compared stroke risk factors, considered to be indicative
      of potential pathogenetic mechanisms, and the clinical outcome of lacunar infarct
      versus nonlacunar infarct patients and those of lacunar syndrome versus
      nonlacunar syndrome patients. RESULTS: Two hundred nineteen patients (42%)
      presented a lacunar syndrome and 298 (58%) a nonlacunar syndrome, while 170 (33%)
      had lacunar infarcts and 347 (67%) nonlacunar infarcts. Lacunar infarct patients
      were more frequently associated with hypertension and a previous transient
      ischemic attack and less frequently with atrial fibrillation when compared with
      their nonlacunar infarct counterparts, whereas no differences were apparent
      between lacunar syndrome and nonlacunar syndrome patients. Logistic regression
      analysis showed that hypertension and a previous transient ischemic attack on the
      one hand and atrial fibrillation on the other were strongly correlated with the
      diagnosis of lacunar infarct and nonlacunar infarct, respectively, while no risk
      factor was correlated with the diagnosis of lacunar syndrome. Twenty-two percent
      of lacunar infarct patients and 68% of nonlacunar infarct subjects had a poor
      outcome (death plus disability of survivors) as opposed to 40% of lacunar
      syndrome and 63% of nonlacunar syndrome patients. Logistic regression selected
      age, severity of neurological deficit at entry, cardiopathies, diabetes, and
      lacunar infarct, but not lacunar syndrome, as predictors of outcome. CONCLUSIONS:
      The inaccurate clinical diagnosis of lacunar infarct made in the first 12 hours
      of stroke might lead to no distinction being made between stroke subgroups with
      potentially different pathogenetic mechanisms and prognostic estimates, thus
      negatively influencing the planning of patient management.

PMID- 7570737
TI  - Undergraduate and postgraduate medical education for cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: There is a perception among some physicians that medical
      students and house officers receive little or no training in the diagnosis and
      treatment of patients with cerebrovascular disease. However, there is a paucity
      of data addressing the issue of medical education in this area. This study was
      performed to determine the quantity and type of undergraduate and postgraduate
      medical education on cerebrovascular disease that is presented to medical
      students and house officers. METHODS: This was a prospective questionnaire study
      sent to 40 mainly academic medical centers in the United States and Canada. Data
      were collected on the percentage of programs offering stroke education,
      percentage of medical students and house officers taking such courses, and the
      duration of teaching programs. RESULTS: Sixty-one percent of the programs had
      dedicated stroke teaching efforts during clinical rotations, averaging a total of
      13.1 hours of didactic and clinical teaching. Medical students received
      approximately 5 hours of preclinical stroke instruction. Only 35% of the programs
      offered stroke training for house officers in their internal medicine program.
      Most programs (81%) offered stroke conferences and computer-based instruction.
      CONCLUSIONS: At some institutions, medical students received a modest amount of
      stroke education during their clinical rotations. However, almost 40% of programs
      did not have required stroke education programs for medical students. Most
      internal medicine programs that we surveyed did not have specific stroke
      education efforts for house officers. Increased educational efforts in this area
      may be indicated.

PMID- 7570736
TI  - Lipoprotein(a) serum concentration and apolipoprotein(a) phenotype correlate with
      severity and presence of ischemic cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Serum lipoprotein(a) [Lp(a)] levels are genetically
      determined and considered to be an independent risk factor for atherosclerosis.
      The aim of this study was to provide a complete analysis of Lp(a) serum levels,
      apolipoprotein(a) phenotypes, and other lipid parameters for different forms of
      severity of symptomatic ischemic cerebrovascular disorders as well as for
      different stages of carotid atherosclerosis. METHODS: Lp(a) concentration,
      apolipoprotein(a) phenotype, triglyceride, low-density lipoprotein, high-density
      lipoprotein, and total cholesterol levels of blind-coded specimens as well as
      degree of carotid artery stenosis were assessed in a consecutive series of
      patients with ischemic cerebrovascular disease. We evaluated 265 male (34%) and
      female (66%) patients (mean age, 51 +/- 7.4 years) with transient ischemic attack
      (55.8%), prolonged reversible ischemic neurological deficits (28.3%), and
      cerebral infarction (15.9%) as well as 288 male (30%) and female (70%) control
      subjects (mean age, 51 +/- 7.1 years). All subjects were white. RESULTS: Lp(a),
      total, and low-density lipoprotein cholesterol were statistically significantly
      elevated in all patients compared with control subjects. Lp(a) correlated with
      the severity of symptomatic cerebrovascular disease and the degree of carotid
      stenosis. Logistic regression analysis revealed Lp(a) as the best single marker
      for the presence of cerebrovascular disease (P < .001) followed by high-density
      lipoprotein cholesterol (P = .003) and triglycerides (P = .049). With a cutoff of
      20 mg/dL of Lp(a), the odds ratio for a subject to have had ischemic stroke with
      elevated Lp(a) was 20.3 and 23.7 depending on the method of the Lp(a) estimation,
      whereas the odds ratio when the sonography score was > 0 was 15.4. The
      investigation of the distribution of the apo(a) phenotypes revealed that 16.73%
      of the control subjects had major isoforms < or = 580 kD molecular weight (B, F,
      S1, S2) versus 42.65% of the patients' group (P < .001). These isoforms were also
      present in 14.71% of all individuals with a sonography score of 0 but in 52.30%
      of all individuals with a sonography score > 0 (P < .001). CONCLUSIONS: This case
      control study shows that an elevated Lp(a) level is the primary factor associated
      with the presence of ischemic cerebrovascular disease and that the increased
      portion of the smaller-molecular-weight apo(a) isoforms in patients and
      individuals with a sonography score > 0 points toward an inherited predisposition
      for this disease.

PMID- 7570738
TI  - Unified Neurological Stroke Scale is valid in ischemic and hemorrhagic stroke.
AB  - BACKGROUND AND PURPOSE: The growing interest in testing new therapeutic agents
      for acute brain injury has lead to increased use of stroke scales. The
      reliability and validity of these measures need to be examined more completely.
      We used structural equation modeling, a technique that merges the analytic
      procedures of factor analysis and multiple regression, to examine the reliability
      and construct validity of the Middle Cerebral Artery Neurological Scale and the
      Scandinavian Neurological Stroke Scale used together as the Unified Neurological
      Stroke Scale. We also analyzed the predictive validity, sensitivity, and
      specificity of the scales in predicting mortality and functional outcome.
      METHODS: We prospectively studied 84 consecutive patients admitted to a
      neurology/neurosurgery intensive care unit with intracerebral hemorrhage (n =
      30), subarachnoid hemorrhage (n = 15), ischemic stroke (n = 15), and traumatic
      brain injury (n = 24). Patients were evaluated within 24 hours of admission and
      at 48-hour intervals until intensive care unit discharge. A total of 386
      assessments were obtained. The Functional Independence Measure was administered
      by telephone 3 months after hospital discharge. RESULTS: High levels of
      reliability and construct validity were observed for the majority of the Unified
      Stroke Scale items. Facial palsy and eye movement items had the lowest
      reliability and validity. Both the Middle Cerebral Artery and Scandinavian Scales
      were significant predictors of outcome. Sensitivity and specificity varied by
      diagnosis. Predictive validity of functional outcome was best in groups with
      ischemic and hemorrhagic stroke rather than traumatic brain injury and
      subarachnoid hemorrhage. CONCLUSIONS: The Unified Stroke Scale demonstrates
      reliability and construct and predictive validity, and its use is supported in
      ischemic and hemorrhagic stroke. Structural equation modeling is an appropriate
      technique for use with scales of this type.

PMID- 7570739
TI  - Amino acid uptake in ischemically compromised brain tissue.
AB  - BACKGROUND AND PURPOSE: Multitracer positron emission tomography (PET) was used
      to investigate local amino acid accumulation in brain tissue surrounding focal
      ischemia. METHODS: PET using 15O-labeled oxygen and water for measuring cerebral
      metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), C15O for
      determination of blood volume (CBV) and calculation of oxygen extraction
      fraction, and L-[11C]methylmethionine (11C-MET) for the assessment of amino acid
      accumulation was applied in 14 patients (mean age, 52 +/- 9.1 years) with acute
      ischemic hemispheric stroke. Two multitracer PET studies were completed, the
      first 8 to 24 hours after onset of neurological symptoms and the follow-up study
      14 +/- 1 days after the ischemic attack. Functional changes were compared with
      morphological damage on cranial CT or MRI. Three-dimensional matching and volume
      of interest evaluation procedures were used to study 11C-MET accumulation in
      relation to various physiological variables in infarcted and noninfarcted tissue.
      RESULTS: Compared with contralateral mirror regions, initially increased regional
      11C-MET uptake (21.2 +/- 10.9%, P < .001) was found in patchy areas in the
      immediate vicinity of infarction as well as in distant areas within the same
      hemisphere. In those areas, regional CBF (-11.4 +/- 21.2%, P < .01) and oxygen
      extraction fraction (2.8 +/- 29.1%, P = NS) were highly variable, and regional
      CMRO2 was preserved or slightly reduced (-12.4 +/- 16.0%, P < .001). CBF data
      comprised severely ischemic as well as high values (14.6 to 64.2 mL/100 g per
      minute). Cranial CT and coregistered MRI in five patients demonstrated preserved
      morphology. In all peri-infarct areas (n = 62), the 11C-MET uptake showed a
      positive correlation with delta CMRO2 as the relative improvement of ipsilateral
      CMRO2 between the two PET studies (r = .378, P < .01). Particularly in areas with
      increased oxygen extraction fraction (n = 42), the 11C-MET uptake showed a mild
      correlation with CMRO2 at follow-up measurement (r = .31, P < .05). In all peri
      infarct areas, 11C-MET uptake showed a negative correlation with oxygen
      extraction fraction (r = -.672, P < .001) and a positive correlation with CBF (r
      = .4, P = .001). In all infarcted and peri-infarct areas, normalized initial 11C
      MET uptake was positively correlated with CMRO2 at follow-up (r = .603, P <
      .001). CONCLUSIONS: Focal increases of 11C-MET uptake seen in this study were
      generally mild. They might be seen in the core of ischemia, indicating breakdown
      of the blood-brain barrier with poor tissue prognosis, but they also frequently
      occurred during or after ischemic compromise in surviving brain tissue
      surrounding focal cerebral infarction, perhaps representing alterations of amino
      acid transport or protein synthesis in brain tissue with a favorable prognosis.

PMID- 7570741
TI  - Angiotensin II contributes to cerebral vasodilatation during hypoxia in the
      rabbit.
AB  - BACKGROUND: and Purpose Hypoxia increases cerebral blood flow (CBF). Hypoxia also
      exerts a major influence on the renin-angiotensin system. In addition to the
      circulating renin-angiotensin system, a local renin-angiotensin system appears to
      be present in the brain, and angiotensin II receptors have been identified in
      cerebral blood vessels. In this study we tested the hypothesis that endogenous
      angiotensin II attenuates dilatation of the cerebral vessels during hypoxia.
      METHODS: Pentobarbital-anesthetized rabbits were prepared for measurement of
      blood flow (microspheres) and assigned to one of two groups: in group 1 (n = 11),
      rabbits were subjected to 30 minutes of stable hypoxia (PaO2 = 34 +/- 1 mm Hg,
      mean +/- SD) followed by 15 minutes of reoxygenation (PaO2 = 177 to 200 mm Hg).
      Blood flow was measured four times: under control conditions, after 15 and 30
      minutes of hypoxia, and after 15 minutes of reoxygenation. This was a control
      group to characterize changes in CBF during hypoxia. In group 2 (n = 11), blood
      flow was measured as in the previous group except that an infusion of the
      angiotensin II receptor antagonist saralasin (1 microgram.kg-1.min-1 IV) was
      started with the onset of hypoxia and continued through reoxygenation to the end
      of the experiment. The goal of this group was to examine whether endogenous
      activation of receptors for angiotensin II influences increases in CBF during
      hypoxia. In a separate series of experiments we examined the influence of the
      angiotensin-converting enzyme (ACE) inhibitor captopril on the hypoxic response.
      Thus, in one group of rabbits we measured CBF in the same manner as in group 1 (n
      = 13). In another group of rabbits we also measured blood flow as in group 1
      except that rabbits received 10 mg/kg of the ACE inhibitor captopril before the
      control measurement (n = 11). We tested for significant differences between
      groups using two-way ANOVA. RESULTS: Under control conditions, CBF was similar in
      all groups and averaged 53 +/- 15 mL.min-1.100 g-1. During hypoxia, CBF increased
      to a greater extent in the absence versus the presence of saralasin (95 +/- 31
      and 104 +/- 30 mL.min-1.100 g-1 versus 72 +/- 24 and 71 +/- 25 mL.min-1.100 g-1,
      respectively; P = .003). Increase in CBF during hypoxia was also significantly
      greater in the animals that did not receive captopril versus those that were
      treated with captopril (100 +/- 24 and 89 +/- 16 mL.min-1.100 g-1 versus 72 +/-
      16 and 73 +/- 17 mL.min-1.100 g-1). To rule out the possibility that saralasin
      produced non-specific attenuation of cerebral vasodilatation, we tested the
      influence of hypercapnia on CBF in the absence and presence of saralasin. During
      normocapnia, CBF values were not significantly different in the absence and
      presence of saralasin (57 +/- 17 and 64 +/- 6 mL.min-1.100 g-1, respectively; P >
      .05). Hypercapnia increased CBF similarly in the absence and presence of
      saralasin (81 +/- 22 and 91 +/- 19 mL.min-1.100 g-1; PaCO2 = 61 +/- 2 and 60 +/-
      2 mm Hg, respectively; P > .05). CONCLUSIONS: Because the ACE inhibitor captopril
      and the angiotensin II receptor blocker saralasin attenuated increased in CBF
      during hypoxia, the findings suggest that endogenous release of angiotensin II
      contributes to the increase in CBF during hypoxia.

PMID- 7570740
TI  - Prevalence and associated features of the cold hemiplegic arm.
AB  - BACKGROUND AND PURPOSE: Some stroke patients complain of an unpleasant sensation
      of coldness in the hemiplegic arm. This study aimed to determine the prevalence
      of this symptom and any associated features. METHODS: A questionnaire about
      symptoms in the arms was sent to patients at least 12 months after stroke. Reflex
      sympathetic dystrophy (RSD) was diagnosed if four typical symptoms were present
      in the arm. RESULTS: One hundred patients were recruited and 75 complete replies
      received. The mean age of the patients was 74 years, and the mean time since the
      stroke was 19 months. Forty patients (53%) experienced unilateral coldness in the
      hemiplegic arm. In 14 this sensation was constant, and 10 rated the symptom as
      troublesome. The symptom developed at a median time of 1 month after stroke, but
      only 13 patients (32%) sought advice from a doctor. Sensory symptoms and arm and
      shoulder pain were common, but the only symptoms associated with coldness were
      numbness (P < .001) and color change (P < .05). Fifteen patients fulfilled the
      diagnostic criteria for RSD, 13 of whom had coldness only in the hemiplegic arm.
      CONCLUSIONS: A sensation of coldness in the hemiplegic arm is common and
      distressing. It is associated with numbness and color changes in the arm. Some
      cases are caused by RSD, but other patients have coldness that may be due to
      other causes such as a vasomotor abnormality.

PMID- 7570742
TI  - Selective depression of endothelium-dependent dilations during cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Pial arterioles have diverse mechanisms for endothelium
      dependent dilations. In mice, different mechanisms or endothelium-derived
      mediators exist for each of the following dilators: acetylcholine, bradykinin,
      and calcium ionophore A-23187. This study tests the response to each of these
      dilators during profound ischemia. The response to sodium nitroprusside, an
      endothelium-independent dilator, was also tested. METHODS: In each mouse,
      ischemia was produced by bilateral carotid artery ligation that reduced cortical
      blood flow by approximately 90% as determined by laser-Doppler flowmetry. In
      separate studies of 10 mice each, dilations of pial arterioles to two doses of
      each dilator were compared before and after 10 minutes of occlusion, with the
      occlusion continuing during the second set of measurements. The dilator was
      applied in the suffusate bathing the pial surface exposed at a craniotomy site.
      Diameters were monitored by in vivo television microscopy and image splitting.
      RESULTS: The dose-dependent dilations to acetylcholine, bradykinin, and calcium
      ionophore A-23187 were each profoundly depressed during ischemia. The response to
      sodium nitroprusside was not depressed. In all cases, the ischemia was
      accompanied by arteriolar narrowing of approximately 25% and by obvious slowing
      of blood flow observed by intravital microscopy. Superoxide dismutase plus
      catalase failed to prevent the depressed response to acetylcholine. CONCLUSIONS:
      Endothelium-dependent dilations, mediated by diverse endothelium-derived relaxing
      factors, are depressed during ischemia of 10 to 15 minutes' duration. This cannot
      be a nonselective effect on vessel responsivity caused by constriction, reduced
      flow, or reduced intraluminal pressure during ischemia because under the same
      conditions dilation to endothelium-independent sodium nitroprusside is preserved.
      The selective endothelial dysfunction may play a role in exacerbating ischemia by
      precluding the ability of some dilators, released during ischemia, to dilate the
      resistance vessels.

PMID- 7570743
TI  - L-deprenyl reduces brain damage in rats exposed to transient hypoxia-ischemia.
AB  - BACKGROUND AND PURPOSE: L-Deprenyl (Selegiline) protects animal brains against
      toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6
      hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents
      or reduces cerebral damage in a transient hypoxia/ischemia rat model. METHODS:
      Rats were treated for 14 days with 2 mg/kg and 10 mg/kg L-deprenyl or saline.
      After surgery a 20-minute hypoxia/ischemia period was induced by simultaneous
      occlusion of the left common carotid artery and reduction of the percentage of
      oxygen in the gas mixture to 10%. Rats were killed 24 hours later. Silver
      staining was used to reveal damage in several brain regions. RESULTS: In the
      brain, both L-deprenyl dosages reduced damage up to 78% compared with the
      controls. Total brain damage was decreased from 23%-31% to 5%-9% with the L
      deprenyl treatment (2 mg/kg: F1.13 = 6.956, P < .05; 10 mg/kg: F1.13 = 5.731, P <
      .05). In the striatum, significant treatment effects were found between both the
      L-deprenyl groups (2 mg/kg and 10 mg/kg, respectively) and the saline group
      (F1.13 = 14.870, P < .005; and F1.13 = 8.937, P = .01; respectively). In the
      thalamus, significant treatment effects were seen in the 2-mg/kg L-deprenyl group
      (F1.13 = 11.638, P < .005) and the 10-mg/kg group (F1.13 = 8.347, P < .05)
      compared with the control group. No significant damage decrease was seen in the
      hippocampus and the cortex. CONCLUSIONS: The results show that L-deprenyl is
      effective as a prophylactic treatment for brain tissue when it is administered
      before hypoxia/ischemia. Mechanisms responsible for the observed protection
      remain unclear. The regional differences in damage, however, are in accordance
      with the reported regional increase in superoxide dismutase and catalase
      activities after L-deprenyl treatment, suggesting the involvement of free
      radicals and scavenger enzymes.

PMID- 7570744
TI  - Reduction of infarct size by intra-arterial nimodipine administered at
      reperfusion in a rat model of partially reversible brain focal ischemia.
AB  - BACKGROUND AND PURPOSE: When blood flow to a brain region that has undergone an
      ischemic attack is reestablished, additional injury is to be expected from the
      reperfusion. The purpose of the study was to determine the effect of the intra
      arterial injection of nimodipine at reperfusion on infarct volume in rats
      subjected to partially reversible focal neocortical ischemia. METHODS: Two groups
      of Long-Evans rats with transient bilateral common carotid artery occlusion and
      permanent middle cerebral artery occlusion were subjected to retrograde
      cannulation of the external carotid artery close to the carotid bifurcation to
      allow the administration of isotonic saline (group 1) or nimodipine solution
      (group 2) just before and during reperfusion. The estimate for the actual amount
      of infarcted cortex was calculated by the volume ratio between the spared cortex
      in the infarcted hemisphere and the total cortex of the contralateral hemisphere
      by means of a serological method based on the Cavalieri principle. RESULTS: The
      percentage of cortex that was infarcted in control rats was 63.8 +/- 3.1%,
      whereas nimodipine-treated rats exhibited a significantly smaller (P < .005)
      percentage of infarct volume (31.3 +/- 12.7%). CONCLUSIONS: Our data show that
      the intra-arterial injection of nimodipine just before and during reperfusion
      reduced neocortical infarct volume in rats subjected to partially reversible
      focal cerebral ischemia.

PMID- 7570745
TI  - Inositol trisphosphate, polyphosphoinositide turnover, and high-energy
      metabolites in focal cerebral ischemia and reperfusion.
AB  - BACKGROUND AND PURPOSE: Although the signaling pathway involving
      polyphosphoinositide (poly-PI) hydrolysis and release of inositol 1,4,5
      trisphosphate [Ins(1,4,5)P3] is an important mechanism for regulation of neuronal
      calcium homeostasis, the effect of cerebral ischemia-reperfusion on this calcium
      signaling pathway is not well understood. Because activity of this pathway is
      dependent on availability of ATP, this study is aimed at examining the poly-PI
      signaling pathway and high-energy metabolites in a rat stroke model. METHODS:
      Focal cerebral ischemia in rats was induced by temporary occlusion of the right
      middle cerebral artery and both common carotid arteries. Levels of Ins(1,4,5)P3
      were determined by use of the radioreceptor binding assay. Poly-PI turnover in
      rat cortex was assessed with an in vivo protocol involving intracerebral
      injection of [3H] inositol and systemic administration of lithium. High-energy
      metabolites (ATP, ADP, and AMP) were analyzed by high-performance liquid
      chromatography. RESULTS: Ischemia induced an increase in poly-PI turnover in the
      right middle cerebral artery cortex, but reperfusion led to a decline in this
      signaling activity. However, Ins(1,4,5)P3 levels decreased during ischemia, and
      these levels were not restored if ischemic insults were longer than 30 minutes.
      ATP levels decreased to 26% of control during ischemia and recovered to 80% of
      control during the initial 4 hours of reperfusion; these changes were followed by
      a second phase of decline. CONCLUSIONS: Results show an important relationship
      between ischemia-induced depletion of high-energy metabolites and poly-PI
      signaling activity. However, the uncoupling between Ins(1,4,5)P3 and ATP during
      reperfusion after severe ischemia suggests that metabolism of Ins(1,4,5)P3 is
      more stringently regulated than ATP.

PMID- 7570746
TI  - Three distinct phases of fodrin proteolysis induced in postischemic hippocampus.
      Involvement of calpain and unidentified protease.
AB  - BACKGROUND AND PURPOSE: Fodrin, a neuronal cytoskeleton protein, is proteolyzed
      by calpain after ischemic insult. We examined proteolysis of fodrin induced by
      global forebrain ischemia in gerbil hippocampus in spatial terms by using the
      antibody specific to the calpain-proteolyzed form of fodrin. METHODS: In gerbils,
      a 10-minute forebrain ischemia was produced by occlusion of both carotid
      arteries. After recirculation, the hippocampus was processed for
      immunohistochemical and immunoblot study with the antibody against the calpain
      proteolyzed form of fodrin. Additionally, short-term ischemia was studied to find
      the threshold of fodrin proteolysis. RESULTS: Three phases of fodrin proteolysis
      distinct in chronology and distribution arose: (1) an early predegeneration phase
      in the molecular layer and stratum oriens of the CA1 and CA3 sectors within the
      first 15 minutes, which lasted up to 4 hours; (2) a late predegeneration phase in
      the whole CA1 sector, except for the pyramidal cells, between 12 hours and 2
      days; and (3) a postdegeneration phase in the cytoplasm of the CA1 neurons, which
      arose in 3 to 7 days. A 4-minute (not a 3-minute) forebrain ischemia induced the
      late predegeneration phase of fodrin proteolysis and delayed neuronal death in
      CA1. Immunoblotting showed that the primary product of calpain action was further
      proteolyzed by an unidentified protease. CONCLUSIONS: Calpain induced proteolysis
      of fodrin in ischemic hippocampus, and the late predegeneration phase of the
      proteolysis was closely associated with the delayed neuronal death in the CA1
      sector. Calpain and another protease may play a role in the development of
      neuronal death after transient forebrain ischemia.

PMID- 7570747
TI  - AMPA antagonist LY293558 does not affect the severity of hypoxic-ischemic injury
      in newborn pigs.
AB  - BACKGROUND AND PURPOSE: LY293558 is a systemically active alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) excitatory amino acid antagonist. AMPA
      antagonists have shown promise in several adult hypoxic-ischemic brain injury
      models, and we wanted to see if this work could be extended to a newborn animal.
      METHODS: Seventy-six (beta error < .10) 0- to 3-day-old piglets under 1.5%
      isoflurane anesthesia underwent placement of carotid snares and arterial and
      venous catheters. While paralyzed with succinylcholine under 0.5% isoflurane, 50%
      nitrous oxide, piglets were randomly assigned to receive either 5 mg/kg or 15
      mg/kg of LY293558 or saline at time--10 minutes and again 10 hours later. At time
      0, both carotid arteries were clamped, and blood was withdrawn to reduce the
      blood pressure to two thirds of normal. At time 15 minutes, inspired oxygen was
      reduced to 6%. At time 30 minutes, the carotid snares were released, the
      withdrawn blood was reinfused, and the oxygen was switched to 100%. On the third
      day after the hypoxic-ischemic injury, the animals were killed by perfusion of
      the brain with 10% formalin. Brain pathology was scored by a blinded observer.
      RESULTS: There were no significant differences between the drug-treated and
      control groups. CONCLUSIONS: The systemically active AMPA antagonist LY293558,
      when given at a dose of 5 mg/kg or 15 mg/kg before injury and 10 hours later,
      does not affect the severity of hypoxic-ischemic brain injury in newborn piglets.
      Neither AMPA receptor activity nor NMDA receptor activity are important in brain
      injury in this model.

PMID- 7570748
TI  - Chronological changes of arterial diameter, cGMP, and protein kinase C in the
      development of vasospasm.
AB  - BACKGROUND AND PURPOSE: We hypothesized that nitric oxide exerts a negative
      feedback control on protein kinase C (PKC) activation, and the disturbance of the
      feedback control after subarachnoid hemorrhage results in vasospasm due to PKC
      activation. This study was undertaken to verify this hypothesis. METHODS:
      Different dogs were prepared for three separate experiments: measurement of the
      angiographic diameter of the basilar artery and determination of cGMP and PKC
      activity in vascular smooth muscle cells. In each experiment, two models were
      used: the single-hemorrhage model for mild vasospasm and the two-hemorrhage model
      for severe vasospasm. In both models, chronological changes of these three
      parameters were examined from day 1 until day 7. RESULTS: In the single
      hemorrhage model, mild vasospasm and a slight decrease of the cGMP level were
      noted on day 4, then both returned to the baseline levels on day 7. PKC activity
      was slightly enhanced throughout the study period. In the two-hemorrhage model,
      severe vasospasm and a significant decrease of the cGMP level were observed on
      day 5 and persisted until day 7. PKC activity was remarkably enhanced from day 5
      until day 7. The differences between the two models with regard to the three
      parameters were statistically significant. CONCLUSIONS: The decrease of cGMP
      level and the enhancement of PKC activity were obviously associated with the
      development of severe vasospasm. We conclude that subarachnoid hemorrhage
      disturbed the feedback control exerted by nitric oxide on PKC activation, leading
      to PKC-dependent vasospasm.

PMID- 7570750
TI  - Alteration of intracellular metabolite diffusion in rat brain in vivo during
      ischemia and reperfusion.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted MRI can demonstrate decreases of the
      apparent diffusion coefficient (ADC) of brain tissue water shortly after the
      onset of ischemia. To further elucidate underlying mechanisms, this study
      extended diffusion assessment to intracellular metabolites in rat brain in vivo
      before, during, and after ischemia. METHODS: Changes in molecular mobility were
      studied in a rat model of global forebrain ischemia (n = 8, 20-minute occlusion,
      120-minute reperfusion) with the use of diffusion-weighted localized proton MR
      spectroscopy. During ischemia and early reperfusion the time course of ADC
      changes was monitored by strongly diffusion-weighted spectra. ADC values of N
      acetylaspartate, creatines, cholines, and myo-inositol were evaluated from series
      of differently diffusion-weighted spectra before ischemia, 90 minutes after
      reperfusion, and 60 minutes postmortem. RESULTS: Parallel to a rise in diffusion
      weighted water signal (133 +/- 20%), pertinent intensities of all brain
      metabolites increased during ischemia. Changes were most pronounced for myo
      inositol (46 +/- 9%) and smallest for N-acetylaspartate (12 +/- 4%). During
      reperfusion water ADC values returned to basal values, whereas metabolite ADC
      values were decreased by 22% (after 40 minutes). Postmortem ADC values (after 60
      minutes) were reduced by 46% for water and 38% for metabolites. CONCLUSIONS: The
      present findings indicate that water ADC changes during ischemic stroke are
      accompanied by significant alterations in intracellular mobility in both neuronal
      and glial cell populations as reflected by N-acetylaspartate and myo-inositol,
      respectively. Altered metabolite ADC values during reperfusion are consistent
      with irreversible tissue damage in this model and offer new means to assess
      circulatory and metabolic compromise.

PMID- 7570752
TI  - Transcranial Doppler ultrasonography and transesophageal echocardiography in the
      investigation of pulmonary arteriovenous malformation in a patient with
      hereditary hemorrhagic telangiectasia presenting with stroke.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is associated with a high
      incidence of pulmonary arteriovenous malformations (PAVMs), which can be the
      underlying cause for cerebral ischemia or brain abscess. The diagnosis of these
      malformations may be difficult, as clinical or radiological findings may be
      absent. Transcranial Doppler ultrasound (TCD) with saline contrast and
      transesophageal echocardiography (TEE) with saline contrast are useful in
      identifying patients with right-to-left shunts and may help identify PAVMs. CASE
      DESCRIPTION: A 68-year-old woman with HHT presented with two strokes over a 1
      year period. After the first stroke, a transthoracic echocardiogram with saline
      contrast demonstrated significant right-to-left shunt that was interpreted as a
      patent foramen ovale. After the second stroke, a TCD contrast study confirmed
      this right-to-left shunt; however, a TEE contrast study discovered an
      extracardiac shunt. Pulmonary angiography revealed a left lower lobe PAVM and
      three telangiectasias involving the right lung. The PAVM was subsequently
      embolized. Postembolization radiographic imaging showed complete occlusion of the
      feeding vessel to the PAVM. However, repeated contrast TCD and TEE demonstrated
      persistent right-to-left shunting. CONCLUSIONS: In our patient, stroke may have
      resulted from peripheral venous emboli passing through the PAVM or from
      endogenous thromboemboli originating within the PAVM. TCD and TEE contrast
      studies were helpful in judging the efficacy of catheter embolization therapy of
      PAVM. TCD and TEE with saline contrast may be clinically useful follow-up
      examinations for recurrence or development of new PAVMs.

PMID- 7570751
TI  - Familial aorto-cervicocephalic arterial dissections and congenitally bicuspid
      aortic valve.
AB  - BACKGROUND: A primary arteriopathy is often implicated in the etiology of
      spontaneous cervicocephalic arterial dissections, but its exact nature usually
      remains unknown. We describe the familial occurrence of spontaneous arterial
      dissections and congenitally bicuspid aortic valve (BAV) and propose a common
      developmental defect in these families. SUMMARY OF REPORT: In the first family, a
      63-year-old man suffered an extracranial internal carotid artery (ICA)
      dissection, and his 43-year-old cousin with BAV suffered an intracranial
      vertebral artery (VA) dissection. Two other family members had pathologically
      proven BAV. In the second family, a 31-year-old woman suffered bilateral
      extracranial ICA and VA dissections. Her father, at age 46, suffered an aortic
      dissection associated with cystic medial necrosis and BAV. Her paternal uncle
      died from an aortic dissection at age 59. In the third family, a 39-year-old
      woman suffered extracranial ICA and VA dissections, and her brother died at age
      48 from an aortic dissection associated with a BAV. CONCLUSIONS: The familial
      occurrence of spontaneous arterial dissections and BAV suggests a common
      developmental defect. The aortic valvular cusps and the arterial media of the
      aortic arch and its branches are derived from neural crest cells, suggesting that
      a neural crest defect may be the underlying abnormality in these families.

PMID- 7570753
TI  - Spontaneous thrombosis of an unruptured anterior communicating artery aneurysm.
      An unusual cause of ischemic stroke.
AB  - BACKGROUND: Stroke caused by spontaneous thrombosis of an unruptured intracranial
      aneurysm is a rare event. CASE DESCRIPTION: A 66-year-old woman experienced a
      transient ischemic attack and cerebral infarctions due to spontaneous thrombosis
      of an unruptured anterior communicating artery aneurysm. Extension of thrombus
      into both anterior cerebral arteries and the left middle cerebral artery,
      resulting in ischemic infarction in all three vascular territories, was diagnosed
      by CT scanning, MRI, and cerebral angiography and confirmed at autopsy.
      CONCLUSIONS: This case illustrates a rare complication of an unruptured saccular
      aneurysm with neuroimaging and pathological correlation. Morphological and
      hemodynamic factors that may have precipitated aneurysm thrombosis are discussed
      with reference to experimental models.

PMID- 7570749
TI  - Structure and function of the rat basilar artery during chronic nitric oxide
      synthase inhibition.
AB  - BACKGROUND AND PURPOSE: Nitric oxide is an important regulator of vascular tone
      and may also be implicated in the modulation of vascular growth and structure.
      This study presents the effects of chronic nitric oxide inhibition, with or
      without antihypertensive treatment, on the structure and function of the basilar
      artery in rats. METHODS: Rats were treated for 6 weeks with N omega-nitro-L
      arginine methyl ester (50 mg/kg per day) alone or in combination with verapamil
      (100 mg/kg per day) or with trandolapril (1 mg/kg per day). Untreated rats served
      as controls. The structure and reactivity of perfused and pressurized basilar
      arteries were analyzed in vitro using a video dimension analyzer. RESULTS:
      Systolic arterial pressure increased only in the nitro-arginine-treated group, as
      did the media-to-lumen ratio of the basilar artery. This structural alteration,
      which was prevented by verapamil and trandolapril, was mainly due to remodeling
      and not to growth. Chronic inhibition of the L-arginine pathway increased the
      response of the basilar artery to serotonin, while the opposite was found for
      endothelin. Verapamil and trandolapril prevented these functional alterations
      that seemed related to the changes in the vascular structure. CONCLUSIONS: The
      remodeling and functional alterations of the basilar artery seem to depend mainly
      on the elevation of arterial pressure with little contribution of the L-arginine
      pathway. Furthermore, nitric oxide does not seem to be implicated in the
      modulation of normal cerebral vascular growth in vivo. However, hypertension
      induced changes in vascular reactivity and structure could alter cerebral blood
      flow and eventually contribute to the development of stroke in this model of
      hypertension.

PMID- 7570754
TI  - Evidence for cardioembolic stroke in a case of Kearns-Sayre syndrome.
AB  - BACKGROUND: Cerebral infarction is a known complication in patients with
      mitochondrial encephalomyopathies (MELAS, MERRF, Kearns-Sayre syndrome), but the
      etiology in the different types remains uncertain. CASE DESCRIPTION: A 33-year
      old woman who had suffered from ophthalmoplegia, bilateral ptosis, ataxia,
      retinitis pigmentosa, and epilepsy since childhood was diagnosed to have Kearns
      Sayre syndrome. The diagnosis was confirmed by muscle biopsy when she was 17
      years old. A pacemaker was implanted because of the occurrence of
      bradyarrhythmias when she was 24 years old. The patient was admitted to the
      hospital with left-sided hemiparesis of sudden onset due to right striatocapsular
      infarction. Results of Doppler sonography of the carotid arteries were normal;
      however, transesophageal echocardiography revealed a thrombus in the left atrial
      appendage. CONCLUSIONS: Stroke in Kearns-Sayre syndrome is likely to be due to
      cardiac embolism. Anticoagulant therapy should be considered even for mild forms
      of cardiomyopathies leading to left ventricular dysfunction.

PMID- 7570755
TI  - Acute fatal deterioration in putaminal hemorrhage.
AB  - BACKGROUND: Clinical deterioration in patients with spontaneous intracerebral
      hemorrhage has rarely been studied. It has been previously thought that
      intracranial hematomas bleed in a monophasic fashion. Recent studies have
      demonstrated continuous active bleeding within hours after the event, resulting
      in enlargement of the hematoma. However, acute sudden and fatal deterioration
      suggesting a rebleed is rarely reported. SUMMARY OF REPORTS: An 84-year-old man
      was admitted with a moderate-size hemorrhage in the putamen and was treated for
      hypertension during the first day of admission. He acutely demonstrated extensor
      posturing and light-fixed pupils. Repeat CT scan showed massive enlargement of
      the intracranial hematoma and extension into the ventricles causing acute
      hydrocephalus. A 72-year-old man was admitted with a mid-size hemorrhage in the
      putamen. Acute deterioration with loss of all brain stem reflexes except for
      cornea reflexes was associated with a large increase in volume of the hematoma, 7
      hours after the initial hemorrhage. An 85-year-old woman was admitted with a
      small hemorrhage in the putamen and recovered to be able to walk unassisted. She
      suddenly died from a recurrent massive putaminal hemorrhage 2 weeks after the
      ictus. CONCLUSIONS: Patients with spontaneous intracerebral hemorrhage in the
      putamen may die acutely from fatal catastrophic enlargement of the initial
      hematoma hours to days after the ictus. In some patients with spontaneous
      intracerebral hemorrhage and clinical deterioration, rebleeding may be a possible
      mechanism.

PMID- 7570756
TI  - Sensory changes in the ipsilateral extremity. A clinical variant of lateral
      medullary infarction.
AB  - BACKGROUND: Classically, patients with unilateral lateral medullary infarction
      exhibit sensory abnormalities over the ipsilateral face and contralateral
      hemibody. As a variant, bilateral or contralateral facial sensory changes can be
      seen. However, sensory changes in the ipsilateral extremities are extremely rare.
      CASE DESCRIPTIONS: We describe three patients with lateral medullary syndrome in
      whom impaired deep sensation in the ipsilateral limbs was found. MRI results
      showed that the infarcts were located superficially in the lateral (case 1) and
      dorsal (cases 2 and 3) areas of the lower medulla, which probably involved the
      ascending or crossing dorsal column sensory tracts. CONCLUSIONS: Although rare,
      impaired ipsilateral deep sensation is encountered in patients with lateral
      medullary infarction syndrome.

PMID- 7570758
TI  - Cerebral autoregulation dynamics in premature newborns.

PMID- 7570757
TI  - Aspirin as a free radical scavenger: consequences for therapy of cerebrovascular
      ischemia.

PMID- 7570759
TI  - Internal carotid artery redundancy is significantly associated with dissection.

PMID- 7570760
TI  - Prognostic value of transcranial magnetic stimulation in acute stroke.

PMID- 7570762
TI  - Telodiencephalic ischemic syndrome (infarct)

PMID- 7570761
TI  - Clinical and laboratory data in heterozygous factor V Leiden mutation positive
      versus negative patients with TIA and minor stroke.

PMID- 7570763
TI  - The Navrongo Community Health and Family Planning Project.
AB  - In 1994, an experiment was launched by the Navrongo Health Research Centre that
      will test the demographic impact of community health and family planning services
      in a rural, traditional area of northern Ghana. While exhaustive social research
      has been directed to clarifying societal constraints to reproductive change,
      relatively little is known about how African cultural characteristics can be a
      resource to family planning programs. This study will clarify ways in which
      cultural resources of a traditional African society can be used in efforts to
      foster reproductive change. This article reviews characteristics of the study
      population, the design of the Navrongo experiment, and the research plan. The
      Navrongo Project will be the first African experimental trial of the demographic
      impact of family planning.

PMID- 7570764
TI  - Withdrawal: a review of the literature and an agenda for research.
AB  - A review to evaluate available literature about withdrawal (coitus interruptus)
      reveals a dearth of research on the current prevalence, acceptability, use
      effectiveness, service-delivery issues, and safety of this ancient and widely
      used temporary contraceptive method. Population and family planning professionals
      are shown to have neglected withdrawal in favor of modern, female-controlled
      methods. This neglect is founded largely upon the popular belief that fertile
      levels of viable sperm are present in pre-ejaculatory fluid, despite data to the
      contrary. The validity of existing data on the prevalence of withdrawal is
      questioned because of the methodological bias inherent in most studies. The use
      effectiveness of the practice and its relationship to sexually transmitted
      diseases have not been adequately investigated. A detailed research agenda on
      numerous topics concerning withdrawal is proposed.

PMID- 7570766
TI  - IUD discontinuation patterns and correlates in four counties in north China.
AB  - This study presents an in-depth analysis of IUD discontinuation patterns and
      correlates in four counties in North China for the years following the
      introduction of provincial family planning regulations and the family planning
      target responsibility system. It is based on contraceptive-use data from 8,630
      rural married women younger than 35. The gross IUD discontinuation rate was low
      among women with one child. The pattern of discontinuation was determined mainly
      by individual demographic profile and institutional variables. IUD users with two
      or more children tended to undergo sterilization after the introduction of the
      regulations of the late 1980s. These counties appear to have been successful in
      shaping couples' contraceptive behavior, but at the expense of individual choice.
      The effect of introducing copper IUDs may be smaller than expected unless
      providers' training is substantially improved and couples' fertility preferences
      altered.

PMID- 7570765
TI  - Quality of care in family planning services in Morocco.
AB  - This study was conducted to heighten awareness of quality of care as a
      programmatic issue in the Moroccan governmental family planning program and to
      test modified Situation Analysis instruments for measuring quality of care. Data
      were collected from 50 service-delivery points in five provinces to measure six
      elements of quality in accordance with the Bruce/Jain framework. A procedure for
      calculating quality-indicator scores is presented. Although facilities varied by
      province and within provinces, most had the equipment and supplies needed to
      deliver services; service personnel were trained and regularly supervised; the
      service-delivery points scored well on mechanisms to ensure continuity of use.
      Notable shortcomings included a dearth of materials for counseling and a
      widespread unavailability of the Ovrette pill. This study raises issues regarding
      the complexity of measuring quality, the ownership of results, and the
      appropriateness of a centralized study of quality in a decentralized program.

PMID- 7570768
TI  - [The determination of the time of death by the content of free amino acids in the
      liver and lungs of cadavers using high-performance liquid chromatography].
AB  - High-performance liquid chromatography is proposed to be used for assessment of
      the time of death during a fortnight postmortem. The procedure consists in
      dynamic measurements of the concentrations of 20 free amino acids in cadaveric
      liver and lungs of subjects dead from mechanical injuries with or without ethanol
      in the blood at moderately high temperatures (18 to 23 C) and 40-60% humidity. A
      working diagram for determination of the time of death is offered and diagnostic
      microblocks consisting of 5 most informative and stable amino acids developed,
      permitting the diagnosis of the time of death with 95% reliability.

PMID- 7570767
TI  - Turkey 1993: results from the demographic and health survey.

PMID- 7570769
TI  - [The dynamics of the amino acid concentration in cadaveric organs in the late
      postmortem period].

PMID- 7570772
TI  - [Mortality from suicides and murders from the forensic medical aspect (based on
      data from Ryazan Province)].
AB  - Based on the files of the Ryazan Regional Bureau of Forensic Medical Expert
      Evaluation and the data of the Regional Statistical Administration, the authors
      analyze the incidence of deaths due to suicides and murders and investigate the
      possibility of predicting these extreme violations in the community. The study
      covers the data on the Ryazan region over the recent decade (1984-1993).

PMID- 7570770
TI  - [The morphological characteristics of the microcirculatory bed of the thymic
      capsule in the dynamics of the posttraumatic period].
AB  - Describes the status of microvessels of thymic capsule in mechanical injury.
      Features the changes occurring in the capsular microvessels in the course of the
      posttraumatic period and the morphology of all the components involved.

PMID- 7570771
TI  - [The possibility of using immunoenzyme analysis for establishing the organ-tissue
      classification of objects in forensic medical expertise].
AB  - The possibility of using enzyme immunoassay for the detection of liver and kidney
      antigens in forensic medical investigations was demonstrated. For this purpose,
      it is necessary to carry out preliminary measurements of protein concentrations
      in a sample and to select working dilutions of antisera used in the test.

PMID- 7570773
TI  - [The results of forensic chemical research in poisoning by barbituric acid
      derivatives].
AB  - Presents the results of forensic chemical analysis of organs from corpses of
      subjects dead from barbiturate poisoning at the site of death and at specialized
      hospitals during rendering specialized medical care. Results of animal
      experiments are presented. The possibility of detecting long-acting barbiturates
      (e.g., phenobarbital) 7 to 9 days after the beginning of detoxifying therapy has
      been demonstrated. A reliable reduction of phenobarbital concentration with
      prolongation of life after poisoning is detected only in investigation of
      experimental animal organs.

PMID- 7570775
TI  - [The possibilities for detecting pelvic injuries in children (comparative x-ray,
      computed tomographic and morphological studies)].
AB  - The authors analyze the possibility of detecting pelvic injuries in children on
      an inpatient basis by x-ray examination and computer-aided tomography and by
      morphological methods during forensic medical autopsy. A total of 146 cases are
      analyzed. X-Ray examination helped diagnose only 47.37% of all injuries in
      children with pelvic traumas. The informative value of the x-ray method may be
      improved if such factors as the presence of residual deformation with manifest
      asymmetry of the small pelvis entry are taken into consideration. If pelvic
      injuries are suspected in children, plane computer-aided tomography is advisable,
      for it permits the diagnosis of 76.32% injuries.

PMID- 7570774
TI  - [The identification of glues in cadaveric material].
AB  - A method for isolation and identification of 21 glues from cadavers has been
      developed. Chromogenic reactions are proposed to be used for identification and
      conditions of chromatography in a thin layer of sorbent developed.

PMID- 7570778
TI  - [A molecular genetic approach to the forensic medical expertise of biological
      relationship at the early stages of embryonic development].
AB  - A new approach to the identification of a father at the early stages of embryonal
      development has been developed, validated, and successfully tried. This approach,
      based on molecular genetic analysis of multiallele loci of human genome using
      polymerase chain reaction is completely justified and advisable for the relevant
      expert evaluations.

PMID- 7570777
TI  - [The determination of toxic compounds with a dinitrophenol structure in
      biological fluids].
AB  - Describes the specific features of chromatographic behavior of numerous toxic
      compounds of dinitrophenol structure in a thin layer of silica gel and in columns
      packed with Silasorb-600 adsorbent for high-pressure liquid chromatography.
      Demonstrates the possibility of using thin-layer and high-pressure liquid
      chromatography for identification and measurements of the above compounds in the
      urine and blood.

PMID- 7570776
TI  - [A combination of chromatographic analysis methods in determining narcotic
      analgesics in biological fluids].
AB  - A combination of instrumental chromatographic methods high pressure liquid
      chromatography in the isocratic mode and reverse phase thin-layer chromatography
      with densitometric ending on Russian Sorbton-RP-2 plates--is conducive to a
      fuller and more reliable identification of narcotic analgesics in biological
      fluids (blood and urine).

PMID- 7570779
TI  - [A case of establishing the reciprocal disposition of the victim and of the fired
      weapon in a wound from a Makarov pistol].

PMID- 7570781
TI  - [Prof. Aleksandr Ivanovich Zakonov (on the 30th anniversary of his death)].

PMID- 7570782
TI  - Attitudes toward the body in suicidal, depressed, and normal adolescents.
AB  - Our purpose was to investigate the hypothesis that suicidal adolescents, compared
      with depressed nonsuicidal and nonsuicidal normal adolescents, display a more
      negative attitude toward their bodies. Scales for suicidal tendencies,
      dissociative tendencies, perception of actual versus ideal body features, and
      feelings toward the body were administered to the subjects. The suicidal subjects
      showed a larger perceived discrepancy between actual versus ideal body features
      and a more negative feeling toward the body, and scored higher on some aspects of
      dissociation than the normal group. The suicidal group also displayed more
      negative feelings toward the body and scored higher on some aspects of
      dissociation than the depressed group. A series of correlations showed that the
      higher the suicidal tendency, the higher the dissociation, the larger the
      discrepancy, and the stronger the negative feelings toward the body. The findings
      were explained as reflecting unique characteristics of suicidal individuals that
      develop from early trauma and sadomasochistic relationships. These
      characteristics may facilitate suicidal behavior.

PMID- 7570783
TI  - Research in adolescent suicide: implications for training, service delivery, and
      public policy.
AB  - Four domains of research in adolescent suicide are reviewed: (1) the role of
      psychopathology, (2) family history of psychopathology, (3) mental health
      treatments, and (4) firearms in the home. Based on the extant literature,
      recommendations are made for changes in training, service delivery, and public
      policy. Among the recommendations for training professionals are: an emphasis on
      diagnostic proficiency, skill and attentiveness in the assessment of the entire
      family unit, and assessment of the availability of firearms in the home. With
      respect to changes in service delivery, we recommend treatment of the entire
      family system, and treatment of psychiatric and substance abuse problems in the
      same setting, and we show the need for a continuum of intensity of care from
      inpatient to outpatient. With respect to policy changes, we recommended parity of
      mental and physical health insurance coverage, screening for psychiatrically at
      risk youngsters in schools and physicians' offices, providing funding to support
      a continuum of care between inpatient and outpatient, and gun control laws to
      restrict access to handguns. We believe that these changes can result in a
      substantial reduction in the adolescent suicide rate.

PMID- 7570780
TI  - [The establishment of the mechanism of the formation of a body wound in a live
      person when there is no evidence].

PMID- 7570784
TI  - Empirically based criteria for rational suicide: a survey of psychotherapists.
AB  - This qualitative study was designed to develop a set of empirically based
      criteria for rational suicide by asking psychotherapists to define "rational
      suicide." Data analysis revealed three components of a rational suicide: (1) the
      presence of an unremittingly hopeless condition (eight examples provided), (2) a
      suicidal decision made as a free choice, and (3) the presence of an informed
      decision-making process (five elements listed). It is suggested that the criteria
      may possibly be used in assessing the rationality of suicidal clients.

PMID- 7570786
TI  - Parental loss and family violence as correlates of suicide and violence risk.
AB  - Seventy-nine psychiatric inpatients were administered a battery of psychometric
      instruments that obtained information about early parental loss, exposure to
      family violence, and behavioral problems in themselves and in their first-degree
      relatives. These variables were correlated with suicide and violence risk
      measures. Suicide risk significantly correlated with all family variables whereas
      violence risk correlated with behavioral problems both in oneself and in one's
      first-degree relatives. Moreover, suicidal and/or violent patients had
      experienced maternal loss significantly more frequently than the
      nonsuicidal/nonviolent patients. In the suicidal/violent group, age of patient at
      death of parents was significantly lower than in the nonsuicidal/nonviolent
      group. Finally, family violence was significantly correlated with behavioral
      problems in self and in first-degree relatives. Findings are interpreted
      according to the authors' theoretical model of aggression regulation.

PMID- 7570785
TI  - Problem solving, stress, and coping in adolescent suicide attempts.
AB  - Twenty adolescents who had made suicide attempts were compared with 20
      nonpsychiatric control subjects on measures of problem solving, stress, and
      coping. The suicidal group did not show evidence of "rigid" thinking or of
      deficits in the ability to generate solutions to standardized interpersonal
      problems. However, they did report recent histories of more severe life stress
      and had inaccurate appraisal of the extent to which stressful events could be
      controlled. Although suicidal patients were able to generate as many adaptive
      strategies as control subjects for coping with their own most severe recent real
      life stressor, they actually used fewer. They were also more likely to identify
      maladaptive behaviors as ways of coping. These findings support a transactional
      model of adolescent suicidal behavior, whereby inaccuracies in the appraisal
      aspects of problem solving (but not in the solution-generation aspects) in the
      face of high life stress lead to a reduction in the use of adaptive efforts to
      cope.

PMID- 7570787
TI  - Intervention styles with suicidal callers at two suicide prevention centers.
AB  - Callers to suicide prevention centers are mainly helped by volunteers trained to
      face these crisis situations. This study evaluated this process of intervention
      in order to better understand the nature of the interventions and their
      determinants. A total of 617 calls with suicidal clients were classified with a
      20-category rating instrument, the Helper's Response List. Cluster analysis
      determined that the 617 intervention profiles could match one of two styles:
      nondirective ("Rogerian" -391 calls) or directive (226 calls). Further analyses
      indicated that the particular style of intervention was related more to the
      characteristics of the callers themselves than to characteristics of volunteers.

PMID- 7570788
TI  - Reducing suicide potential among high-risk youth: tests of a school-based
      prevention program.
AB  - This study tested the efficacy of a school-based prevention program for reducing
      suicide potential among high-risk youth. A sample of 105 youth at suicide risk
      participated in a three-group, repeated-measures, intervention study.
      Participants in (1) an assessment plus 1-semester experimental program, (2) an
      assessment plus 2-semester experimental program, and (3) an assessment-only group
      were compared, using data from preintervention, 5-month, and 10-month follow-up
      assessments. All groups showed decreased suicide risk behaviors, depression,
      hopelessness, stress, and anger; all groups also reported increased self-esteem
      and network social support. Increased personal control was observed only in the
      experimental groups, and not in the assessment-only control group. The potential
      efficacy of the experimental school-based prevention program was demonstrated.
      The necessary and sufficient strategies for suicide prevention, however, need
      further study as the assessment-only group, who received limited prevention
      elements, showed improvements similar to those of the experimental groups.

PMID- 7570792
TI  - Standards of care.

PMID- 7570791
TI  - Retributive rage: the case of Roger.

PMID- 7570789
TI  - Negative attributional style for interpersonal events and the occurrence of
      severe interpersonal disruptions as predictors of self-reported suicidal
      ideation.
AB  - We applied the hopelessness theory of depression to suicidal symptoms: 203
      undergraduates completed questionnaires on attributional style, negative life
      events, hopelessness, and suicidal symptoms at one point in time and again 10
      weeks later. Consistent with prediction, the combination of a negative
      attributional style for interpersonal events and the occurrence of such events
      were prospectively related to increases in self-reported suicidality over the
      course of the 10-week study. These findings displayed specificity with respect to
      interpersonal versus achievement-related styles and events. Contrary to
      hypothesis, hopelessness did not mediate the relation between the Attributional
      style x Stress interaction and the increases in self-reported suicidality.

PMID- 7570790
TI  - Cross-validation of the five-factor interpretive model of the Suicide Opinion
      Questionnaire.
AB  - This study is a cross-validation analysis of the five-factor interpretative model
      of the Suicide Opinion Questionnaire (Domino, Moore, Westlake, & Gibson, 1982)
      reported by Rogers and DeShon (1992). Results indicated moderate support for the
      five-factor model. That is, although the factor analysis results generally
      supported the 5-factor model, a number of items loaded equally well across 2 or
      more factors. Additionally, internal consistency and test-retest reliabilities
      ranged from .48 to .85 and from .34 to .92, respectively, indicating weaknesses
      in some of the subscales. Strategies are suggested for the future psychometric
      development and refinement of the instrument.

PMID- 7570794
TI  - [Minister Borst supports geriatrics].

PMID- 7570793
TI  - Suicide.

PMID- 7570796
TI  - [The Mini Mental Status Examination. Normative data and a comparison of a 12-item
      and 20-item version in a sample survey of community-based elderly].
AB  - The results of a study on the comparison of the original 20-item Mini-Mental
      State Examination with a shortened 12-item version as a brief screening test for
      cognitive impairments in a community based older sample are presented. The scores
      on the MMSE decrease with higher ages and lower levels of education. The results
      show that a threshold value of 24 on the MMSE-20 (Cohen's kappa .70), which
      supports previous Norwegian findings. In case of the identification of older
      people with severe cognitive impairments -threshold value 17 or 18 on the MMSE-20
      , we found a corresponding threshold on the MMSE-12 of 7 (Cohen's kappa .87 and
      .91, respectively). Although the Norwegian researchers made no direct comparison
      between the MMSE-20 and MMSE-12 for these lower thresholds, a threshold 7 on the
      MMSE-12 resulted in a lower level of misclassifications of cognitively impaired
      patients by a psychogeriatrician compared to a threshold of 18 on the MMSE-20. It
      may be concluded that the MMSE-12, which is simpler to use and takes less time,
      has the same diagnostic properties as a screening tool for mild and severe
      cognitive impairments.

PMID- 7570798
TI  - The influence of age and gender on the outcome of total knee arthroplasty.
AB  - 1. The influence of age and gender on the outcome of total knee arthroplasty was
      examined in 762 knees (490 patients). 2. Gender was shown not to significantly
      affect the outcome of total knee arthroplasty. Age was observed to produce a
      significant difference. 3. These results confirm the clinical expectation that
      both male and female older patients can expect equally favorable outcomes
      following total knee arthroplasty.

PMID- 7570797
TI  - [Gait disorders and repeated falls in Steele-Richardson-Olszewski syndrome].
AB  - Progressive supranuclear palsy (syndrome of Steele-Richardson-Olszewski)
      represents one of the neuro-degenerative diseases, difficult to distinguish from
      other forms of parkinsonism. Although uncommon, the syndrome should be included
      in the differential diagnosis of recurrent falls in the elderly, especially in
      cases of parkinsonism presenting with axial rigidity and associated with gaze
      paralysis and/or poor response to L-dopa-therapy. The diagnosis is mainly based
      on the clinical findings. At present, no effective therapy is known.

PMID- 7570800
TI  - The Oklahoma City bombing: surgical response inside and outside the OR.

PMID- 7570795
TI  - [Informed consent and mental competence of the elderly in medical-scientific
      studies].
AB  - The decision whether a potential subject is competent or incompetent is a
      necessary and crucial part of conducting medical research in the elderly. The
      assessment of competency is required by the legal and ethical frameworks in which
      this research has to take place. The state of play in the national and
      international discussions of bills for legislation of this topic will be
      summarized. Especially the practical consequences of this forthcoming legislation
      for researchers will be explained. The ethical framework for medical research
      with elderly subjects will be described from a historical point of view. By means
      of a review of relevant literature the legal definition of competency will be
      operationalized and tests for its assessment will be discussed. Competency of
      consent is assessed by asking several questions about the essential elements of
      the study. The introduction of a try out of the study for a subject before asking
      consent ('experienced consent') is propagated as a method to optimize this
      consent of elderly subjects. Special conditions for giving the required
      information to elderly subjects, for the informed consent by proxy and for the
      inclusion of nursing-home residents, are discussed.

PMID- 7570799
TI  - Anesthetic considerations for pediatric ophthalmologic surgery.
AB  - 1. Although many adult ocular procedures may be done equally well under local or
      general anesthesia, with children, the anesthesiologist almost always has to
      administer general anesthesia to guarantee satisfactory surgical conditions. 2.
      Patient preparation includes parental understanding of the procedure, the
      anesthetic and its implications, and the care of the postoperative child. In
      general, anesthetic induction is accomplished in an age-appropriate fashion. 3.
      Basic discharge criteria include the following: Vital signs should be stable and
      normal; there should be no signs of respiratory distress; mental status should be
      age-appropriate and back to baseline; the patient should demonstrate the ability
      to either swallow fluids, cough, or have an intact gag reflex; the patient should
      be able to ambulate, if age-appropriate and baseline; and the patient always must
      have a responsible, well-informed escort home. engaging and diverting; have a
      collection of stories or songs ready.

PMID- 7570802
TI  - Assuring trauma system quality by outcomes reporting in two voluntary regional
      trauma networks.
AB  - 1. Providing optimal trauma care for large populations requires the collaboration
      and cooperation of hospitals providing all levels of care. 2. Those who are
      seriously injured or who have complex injuries requiring special resources are to
      be referred in a timely fashion to a trauma center capable of providing optimal
      care. 3. In two regional trauma networks, 24% of injured patients were referred
      to a trauma center for definitive care. Overall survival was excellent.

PMID- 7570804
TI  - Telephone triage program: nurses respond to calls from patients recovering at
      home.

PMID- 7570801
TI  - Protecting your eyes in the laser operating room.
AB  - 1. Laser protective eyewear is nearly as important to the OR nurse as the
      surgical mask in an operating room where laser surgery is performed. 2. Most
      hospitals require OR personnel to wear protective eyewear during laser procedures
      in voluntary compliance with American National Standards Institute (ANSI) Z136.3
      for the safe use of lasers in health care facilities. 3. The basic steps to
      protecting your eyes are as follows: Select the appropriate eyewear (plastic or
      glass); make sure the eyewear fits properly; wear the protective lenses during
      laser testing and operation; and heed your laser safety officer.

PMID- 7570803
TI  - Easing surgical and procedural pain in children.

PMID- 7570806
TI  - A brief discussion of nurse practice acts.

PMID- 7570805
TI  - We can wait no longer for health care reform--it's here!

PMID- 7570808
TI  - A 'new' parasite: human infection with Cyclospora cayetanensis.

PMID- 7570809
TI  - Prevalence of malaria in Afghan refugee villages in Pakistan sprayed with
      lambdacyhalothrin or malathion.

PMID- 7570810
TI  - The control of Culex quinquefasciatus breeding in septic tanks using expanded
      polystyrene beads in southern Tanzania.

PMID- 7570807
TI  - Endoscopic anterior cruciate ligament reconstruction. Endobutton/button--a method
      of endoscopic fixation.
AB  - 1. Reconstruction of the anterior cruciate ligament may be accomplished in many
      ways using a variety of autologous as well as allograft tissue. 2. A method of
      fixation uses an Endobutton for femoral fixation and a 19 mm Hewson Ligament
      Button for the tibial fixation of the graft. 3. This method of fixation will
      permit the surgeon to choose the graft best suited to the patient's needs while
      allowing endoscopic reconstruction of the anterior cruciate ligament, regardless
      of the choice of graft. Fixation of the graft need no longer be a variable in
      anterior cruciate ligament reconstruction.

PMID- 7570812
TI  - An urban outbreak of visceral leishmaniasis in Natal, Brazil.
AB  - The epidemiological pattern of visceral leishmaniasis in north-eastern Brazil is
      changing. The disease was typically seen in rural, endemic areas, but is now
      occurring as an epidemic in the city of Natal where 316 cases have been reported
      since 1989; 49% were in children less than 5 years of age. The principle clinical
      and laboratory findings were weight loss, fever, hepato-splenomegaly, anaemia,
      leucopenia and hypergammaglobulinaemia. Elevated transaminases and
      hyperbilirubinaemia were also observed. The diagnosis was confirmed in 87% of
      cases by identifying amastigotes in aspirates from bone marrow or spleen. Five
      isolates were identified as Leishmania (L.) chagasi by isoenzyme analysis. The
      mortality rate was 9%; all deaths occurred during the first week in hospital. One
      person had concurrent human immunodeficiency virus infection. Among 210 household
      contacts and neighbours of patients from the endemic area examined for evidence
      of L. (L.) chagasi infection, 6 additional cases of visceral leishmaniasis were
      diagnosed. Thirty-eight percent of house-mates and neighbours gave a positive
      Montenegro skin test reaction, indicating prior subclinical infection.

PMID- 7570811
TI  - Patterns of malaria morbidity and mortality in children in northern Ghana.
AB  - A malaria prevalence survey was carried out in young children in northern Ghana
      between October 1990 and September 1991, in an area with continuous mortality and
      morbidity surveillance. There was marked seasonal variation in malaria deaths,
      reported fevers, parasite rates and mean parasite densities, with parasite rates
      reaching 85-94% in the wet season. The monthly numbers of malaria deaths were
      highly correlated with rainfall in the previous 2 months (r = 0.90, P < 0.001).
      Parasite rates were highest in the oldest children (5-7 years), but parasite
      densities and rates of febrile illness were highest in those 6-11 months old.
      Haemoglobin levels were also at their lowest in this age group. The predominant
      species, Plasmodium falciparum, was present in 71% of all blood films. Febrile
      illness was well recognized by mothers, but it was not possible to construct a
      simple clinical diagnostic algorithm which would identify even 50% of children
      with high levels of malaria parasitaemia (> or = 4000 parasites/microL).
      Malariometric indicators appear to have changed little in this area since a
      previous survey in 1955.

PMID- 7570813
TI  - The fall and rise of Andean cutaneous leishmaniasis: transient impact of the DDT
      campaign in Peru.
AB  - A retrospective analysis was carried out on census data collected from house-to
      house surveys during 1991-1992 in 4 areas endemic for Andean cutaneous
      leishmaniasis (uta) in the Department of Lima, Peru. Major changes in mean annual
      incidence in susceptible persons have taken place in these sites during the last
      60 years. In particular, there is strong support for the hypothesis that, from
      the 1950s to the 1970s, the transmission rate was temporarily suppressed, largely
      as a by-product of the DDT house spraying campaign against malaria. These results
      are consistent with (i) anecdotal evidence, contemporary with the spraying
      campaign, and (ii) the official Ministry of Health records for the annual number
      of uta cases in the Departments of Lima and Ancash.

PMID- 7570814
TI  - HIV-Leishmania co-infection in Portugal: isolation of Leishmania infantum MON-24.

PMID- 7570816
TI  - HTLV-1 infection and tropical spastic paraparesis in Esmeraldas Province of
      Ecuador.

PMID- 7570815
TI  - A second community outbreak of waterborne giardiasis in Canada and serological
      investigation of patients.
AB  - A waterborne outbreak of giardiasis which occurred 5 years after another in the
      same town in Canada was investigated. Sera from residents defined as cases or non
      cases were tested by enzyme-linked immunosorbent assay (ELISA) and compared with
      sera from symptomatic and asymptomatic control groups. The outbreak-associated
      Giardia isolate was retrieved from contaminated drinking water and antigen from
      this strain was used in the serological investigation. Up to 84% of cases were
      identified by ELISA. More cases were identified by elevated immunoglobulin (Ig) G
      than by either elevated anti-Giardia IgA or IgM levels. Residents of the
      community infected during the first outbreak were significantly less likely to
      have been reinfected during the second outbreak. This is the first report of a
      second waterborne outbreak occurring in a community and results of the
      investigations are consistent with an acquired, protective immunity lasting at
      least 5 years.

PMID- 7570818
TI  - Schistosomiasis in the Republic of Sao Tome and Principe: human studies.
AB  - The only schistosome species found in stool specimens in the local population of
      the republic of Sao Tome is Schistosoma intercalatum. An initial survey of
      schoolchildren showed an overall prevalence of 10.9%, with some schools reaching
      29%. No S. haematobium egg was found in 782 urine specimens from the local
      population, although some were seen in the urine of Angolan soldiers stationed
      near the capital city. One village in the endemic area, San Marcal, had an S.
      intercalatum prevalence of 43%, with 14 persons > 40 years of age harbouring
      severe infections. The transmission area is restricted to the north-east of the
      main island, where 5 foci apparently account for most of the infections. Seven
      cases recorded from Principe may be explained by the fact that the children were
      attending school at Sao Tome. Women carrying out domestic activities are more at
      risk of contracting the infection because of longer periods of water contact than
      men. The morbidity produced by the infection is restricted to splenomegaly and
      blood in the stools. High prevalences have been found of Ascaris lumbricoides and
      Trichuris trichiura, and hookworm and Stronglyloides stercoralis were also
      observed. Praziquantel was well tolerated and appears to be a good tool for
      control purposes, although reinfection in the transmission area apparently occurs
      rapidly. Control strategies based on chemotherapy should take into account an
      older age group as well as the schoolchildren. Focal mollusciciding and the
      introduction of washing facilities may also have a role to play in control. The
      possible recent introduction of the infection to the island is discussed.

PMID- 7570820
TI  - Apparent absence of Lyme borreliosis in Zimbabwe.

PMID- 7570821
TI  - Gastroduodenal diseases on the Jos plateau, Nigeria.
AB  - Two hundred and forty-three Nigerian patients referred for endoscopy at the Jos
      University Teaching Hospital in Nigeria were studied. Their overall mean age was
      37.7 years (SD 12.7), among those with ulcers it was 38.4 years. The male:female
      ratio was equal in general, but among those with ulcers it was 2:1. Duodenal and
      gastric ulcers were found in 42(17.3%) and 12(4.9%) patients respectively, ratio
      of 3.5:1. There were 3 patients each with oesophageal and gastric carcinoma. Our
      findings do not support the belief that the savannah region of West Africa is an
      area of low prevalence of peptic ulcer disease. In the light of the importance of
      Helicobacter pylori infection in the pathogenesis of gastroduodenal diseases and
      the apparent discrepancy between its prevalence and that of associated diseases
      in the developing countries, there is a need to reappraise our traditional
      beliefs about the epidemiology of these diseases, using similar methods to those
      used in developed countries.

PMID- 7570817
TI  - Preliminary study of urinary schistosomiasis in a village in the delta of the
      Senegal river basin, Senegal.
AB  - Three years after the first cases of urinary schistosomiasis infection were
      reported in the village of Mbodiene, Senegal, Schistosoma haematobium eggs were
      found in 87% of the inhabitants of this village; 30% were heavily infected (> 50
      eggs per 10 mL urine). The prevalence of infection was very high in all age
      groups, but children showed more intense infections. No difference between sexes
      was found. In the special situation of a very high prevalence, test strips for
      proteinuria and haematuria are not very useful for the individual diagnosis of S.
      haematobium infection. Six and 12 weeks after treatment with a single dose of
      praziquantel (40 mg/kg), S. haematobium eggs were found in 25% and 30% of the
      treated subjects, respectively. Bulinus globosus was identified as intermediate
      host, but other snail vectors may also play a role. S. mansoni eggs were found in
      1% of the population. Both S. haematobium and S. mansoni are spreading in the
      delta of the Senegal river.

PMID- 7570819
TI  - Seroprevalence of HTLV-1 in chronic disease patients in Jamaica.
AB  - A high seropositivity rate of human T cell lymphotropic virus type 1 (HTLV-1)
      infection was found in Jamaican patients with chronic diseases. However, except
      for tropical spastic paraparesis, polymyositis, adult T cell leukaemia/lymphoma
      and polyneuropathies of undetermined cause, HTLV-1 seropositivity rates in
      chronic disease patients were not significantly different from that found in
      healthy Jamaicans. These results indicate that there is no increased risk of HTLV
      1 infection or HTLV-1 associated disease in patients with chronic diseases
      compared to the general Jamaican population. The association of unclassified
      polyneuropathies with HTLV-1 reported herein is a novel one which requires
      further studies to elucidate its nature.

PMID- 7570822
TI  - High incidence of oesophagus and stomach cancers in the Bale highlands of south
      Ethiopia.

PMID- 7570823
TI  - QBC and thick blood films for malaria diagnosis under field conditions.

PMID- 7570826
TI  - Serodiagnosis of cysticercosis: specificity of different antigens and enzyme
      linked immunosorbent assays.

PMID- 7570824
TI  - Laboratory diagnosis of malaria by village health workers using the rapid manual
      ParaSight-F test.

PMID- 7570825
TI  - A comparison of parasitological methods for the diagnosis of gambian
      trypanosomiasis in an area of low endemicity in Cote d'Ivoire.
AB  - The card agglutination test for trypanosomiasis (CATT) was used to examine 8974
      inhabitants in 14 village areas south-west of Daloa, Cote d'Ivoire; 114 (1.3%)
      were CATTT or +/-, and were further examined by one or more of 6 methods for the
      direct detection of trypanosomes: lymphatic gland puncture, stained thick blood
      film (TBF), haematocrit centrifugation technique (HCT), mini-anion exchange
      column (MAEC), quantitative buffy coat method (QBC), and kit for in vitro
      isolation of trypanosomes (KIVI). Trypanosomes were seen by at least one method
      in 16 (14.0%) of the CATT+ group. Blood from 356 of the 8860 CATT- group was
      inoculated into KIVI; trypanosomes grew from the blood of 1 person. Eleven of the
      17 patients with detectable trypanosomes were screened by all 6 methods: 6 were
      HCT+; 7 were gland+; 10 were MAEC+; 10 were KIVI+; 11 were both TBF+ and QBC+.
      One CATT+ patient was KIVI+ but otherwise negative, although TBF was not done.
      The overall prevalence of trypanosomes was 0.2% rising to 0.8% in one village
      area. The results support previous evidence that a reappraisal of procedures is
      required in the customary system of surveillance for gambian sleeping sickness.

PMID- 7570827
TI  - A comparative study of three methods of detection of Borrelia crocidurae in wild
      rodents in Senegal.
AB  - In a rural area in Senegal with a high incidence of tick-borne relapsing fever in
      humans, Borrelia crocidurae was studied in the blood and brain of wild rodents
      (Mastomys erythroleucus, Arvicanthis niloticus and Rattus rattus) using 3
      methods: (i) direct examination of thick blood films; (ii) intraperitoneal
      inoculation of blood into white mice; (iii) intraperitoneal inoculation of
      homogenized cerebral tissue into white mice. Of the 82 rodents examined, the
      proportion of infected animals was respectively 2.4%, 7.3% and 14.6% for each
      method, and 18.3% for all 3 methods combined. Of the 12 animals with infected
      cerebral tissue, only 3 were found to have infected blood. These results suggest
      that isolated infections of the brain occur frequently in Senegalese wild
      rodents. Measurement of the real prevalence of B. crocidurae should therefore
      take into account these infections in addition to blood infections.

PMID- 7570829
TI  - Convulsions in childhood malaria.
AB  - A retrospective survey was conducted of all 2911 children admitted with malaria
      to 4 provincial hospitals in eastern Thailand between 1977 and 1987. 96 (3.3%)
      had cerebral malaria of whom 21 (22%) died, 225 (7.7%) had convulsions but were
      not comatose (4 died), and 2590 were conscious and had no fits (5 died). Thus the
      relative risk of a fatal outcome associated with convulsions, in the absence of
      cerebral malaria, was 9.2 (95% confidence interval [CI] = 2.5-34.1), P = 0.004.
      Overall, Plasmodium falciparum caused 81% of infections, P. vivax 16%, and 3%
      were mixed. Convulsions without cerebral malaria were more common in children
      under 3 years old (16%) compared with older children (3%): relative risk 5.6 (95%
      CI = 4.2-7.5), and were significantly associated with falciparum malaria (8.3%)
      compared with vivax malaria (4.7%): relative risk 1.7 (95% CI = 1.1-2.7).
      Convulsions are an important complication of malaria in young children, and are
      associated specifically with P. falciparum infection, even in otherwise
      uncomplicated malaria.

PMID- 7570830
TI  - Diurnal variation in body temperature of Gambian children.
AB  - Measured fever often forms the basis for defining clinical malaria episodes in
      children from endemic areas. We measured body temperature every 3 h from 08:00 to
      20:00 in 69 children aged 1-5 years during the malaria season in a rural area of
      The Gambia. Body temperature varied on average by more than one degree Celsius
      during the course of a day. Mean temperatures were lowest in the early morning
      and highest in the afternoon. There was a strong positive association between air
      temperature and body temperature. In highly endemic areas, researchers who use
      measured fever to assess clinical malaria episodes in population-based surveys
      should standardize the time of day at which temperature is assessed.

PMID- 7570828
TI  - Specificity of Cholera Screen test during an epidemic of cholera-like disease due
      to Vibrio cholerae O139 synonym Bengal.

PMID- 7570831
TI  - An outbreak of acute kala-azar in a nomadic tribe in western Sudan: features of
      the disease in a previously non-immune population.

PMID- 7570832
TI  - The effect of targeted chemotherapy against ascariasis on the height of children
      in rural Myanmar.

PMID- 7570834
TI  - 'Typhoid hepatitis' or typhoid fever and acute viral hepatitis.

PMID- 7570833
TI  - Epidemic AIDS-related Kaposi's sarcoma in southern Africa: experience at the
      Johannesburg General Hospital (1980-1990).
AB  - Epidemic acquired immune deficiency syndrome-related Kaposi's sarcoma (AKS) in
      tropical and southern Africa is a highly varied neoplastic disease, characterized
      by multifocal mucocutaneous, lymphatic and visceral involvement. It follows a
      clinical course similar to AKS in Europe and the USA. However, lack of adequate
      medical facilities in many African countries hampers successful palliation of
      this fatal disease. In this retrospective analysis, we summarize our experience
      with 52 patients with AKS treated at Johannesburg General Hospital, South Africa,
      between 1980 and 1990. Radiation therapy can provide good to excellent palliation
      with only minimal side-effects, producing a lesser impact on the haematological
      and immunological system than chemotherapy.

PMID- 7570836
TI  - Studies of infection with Vibrio cholerae O139 synonym Bengal in family contacts
      of index cases.

PMID- 7570835
TI  - The clinical pattern of diarrhoeal illness caused by the new epidemic variant of
      non-O1 Vibrio cholerae.

PMID- 7570837
TI  - Plasmodium falciparum: susceptibility in vitro and in vivo to chloroquine and
      sulfadoxine-pyrimethamine in Ghanaian schoolchildren.
AB  - In Ghana, resistance of Plasmodium falciparum to chloroquine was observed for the
      first time in 1986. By the end of 1991 it had reached a high frequency and a
      substantial degree. A combined study in vivo and in vitro of the response of P.
      falciparum to chloroquine and sulfadoxine/pyrimethamine was carried out in
      Madina, Accra, in the coastal area of Ghana, late in 1991. 96 valid tests in vivo
      were performed with children and adolescents. There were 52 successful tests in
      vitro with chloroquine, and 52 with sulfadoxine/pyrimethamine. 45% of the
      chloroquine tests in vivo and 37% of the sulfadoxine/pyrimethamine tests in vivo
      indicated RII/RIII resistance. Results in vivo and in vitro were significantly
      correlated. The presence of RIII responses, 9% with chloroquine and 14% with
      sulfadoxine/pyrimethamine, indicates a need for third-line antimalarial drugs,
      the unregulated use of which may entail the risk of early and rapid occurrence of
      multi-resistance.

PMID- 7570839
TI  - The effect of cocaine on the growth of Plasmodium falciparum in vitro.

PMID- 7570838
TI  - Inverse correlation of sensitivity in vitro of Plasmodium falciparum to
      chloroquine and mefloquine in Ghana.

PMID- 7570841
TI  - Rectal administration of chloroquine for treatment of children with malaria.

PMID- 7570840
TI  - Stabilization of chloroquine resistance in vivo of Plasmodium falciparum in Edea,
      south Cameroon.

PMID- 7570843
TI  - Hepatotoxicity of sodium stibogluconate therapy for American cutaneous
      leishmaniasis.
AB  - Sodium stibogluconate is the mainstay of treatment for all forms of
      leishmaniasis. Therapy is associated with an increase in serum aminotransferases.
      In this study liver damage was assessed during treatment of American cutaneous
      leishmaniasis with sodium stibogluconate and also in a control group given
      aminosidine. In addition to standard liver function tests, acute hepatocellular
      damage was assessed by measuring plasma glutathione S-transferase B1 (GST), and
      hepatic metabolic capacity was assessed by a caffeine clearance (CCL) test,
      before, during and after treatment. Thirteen patients were treated; 5 received
      sodium stibogluconate, 6 received aminosidine and a further 2 patients received
      aminosidine followed by sodium stibogluconate. Treatment with sodium
      stibogluconate was associated with an increase in both alanine aminotransferase
      (ALT) and GST and a fall in the CCL, indicating both hepatocellular damage and
      functional impairment. Six weeks after treatment had stopped ALT and GST had
      returned to pre-treatment levels and the CCL remained depressed in only one
      patient. Patients given aminosidine did not show any evidence of liver damage.
      Sodium stibogluconate is associated with significant hepatocellular damage and
      hepatic functional impairment. However, this is rapidly reversible on drug
      withdrawal. We suggest that liver function is monitored throughout treatment and
      that patients with pre-existing liver disease receive alternative treatment.

PMID- 7570844
TI  - The effect of ivermectin treatment on the antibody response to antigens of
      Onchocerca volvulus.
AB  - The effect of the microfilaricidal drug ivermectin on the antibody response to a
      detergent extract of adult Onchocerca volvulus (OvAg) and a number of specific
      recombinant peptides was examined. Three of the peptides were combined in a
      serodiagnostic 'cocktail' and the effect of ivermectin on the diagnostic
      performance of this assay was assessed. Immunoglobulin (Ig) G1 serum levels in
      response to OvAg significantly decreased following ivermectin treatment. The
      antibody response to only one recombinant peptide (OvMBP29) was significantly
      affected, with IgG levels decreasing following treatment. Levels of total IgE
      increased following treatment. No correlation was observed between initial
      antibody level (or change in antibody level) and any adverse reaction to
      treatment. The serodiagnostic 'cocktail' was 100% sensitive before and after the
      use of ivermectin. A serodiagnostic assay using specific recombinant peptides can
      be used to evaluate infection in the absence of dermal microfilariae in areas
      where ivermectin is used.

PMID- 7570842
TI  - Gambiense trypanosomiasis: frequency of, and risk factors for, failure of
      melarsoprol therapy.
AB  - 1083 patients with late-stage Trypanosoma brucei gambiense sleeping sickness were
      treated with melarsoprol in Nioki hospital, Zaire, between 1983 and 1990. Sixty
      two (5.7%) died during treatment. Of the 1021 patients who survived the
      treatment, 63 (6.2%) subsequently relapsed, 58 (92%) of whom were diagnosed
      within 2 years of melarsoprol treatment. There was no evidence of an increase in
      the frequency of treatment failures during the study period, and the rate of
      relapses that we documented is comparable to that reported from Zaire more than
      30 years ago. Relapses were more frequent among patients who had trypanosomes
      seen in the cerebrospinal fluid (CSF) at the time of the initial diagnosis (odds
      ratio [OR] = 2.76, 95% confidence interval [CI] = 1.65-4.63, P = 0.0001). Male
      patients had twice as many relapses as females (OR = 2.00, 95% CI = 1.19-3.36, P
      = 0.009), which was partly explained by males having trypanosomes in the CSF more
      often than females. There were important geographical variations in the frequency
      of relapses within the territory of the Nioki rural health zone, suggesting that
      the circulation of trypanosomes was geographically limited. Prednisolone
      treatment did not increase the risk of treatment failure, nor did decreasing the
      total dose of melarsoprol from 12 to 9 injections for patients with > or = 100
      white blood cells/mm3 of CSF. Since patients with trypanosomes in the CSF are
      also those who are at the highest risk of melarsoprol-induced encephalopathy,
      more aggressive treatment regimens cannot be recommended.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7570849
TI  - The use of isoelectric focusing on polyacrylamide gel for the enzymatic analysis
      of 'Old World' Leishmania species.
AB  - Using isoelectric focusing (IEF), a high resolution electrophoresis technique, we
      analysed 6 enzymes of 24 cloned strains representing all major taxa of 'Old
      World' Leishmania. The comparison of enzymatic patterns obtained with IEF and
      starch gel electrophoresis showed that IEF is a more discriminatory and more
      informative technique for the enzymatic analysis of Leishmania strains; it can
      detect very slight differences between 2 electromorphs not revealed with starch
      gel electrophoresis. Moreover, IEF detected several multi-banded patterns which
      appeared as single bands with starch gel electrophoresis. These multi-banded
      patterns could not be the result of strain heterogeneity since all the strains
      had been cloned. Their significance in the biology of Leishmania is discussed.

PMID- 7570845
TI  - Advantages of ivermectin at a single dose of 400 micrograms/kg compared with 100
      micrograms/kg for community treatment of lymphatic filariasis in Polynesia.
AB  - In April and October in 1991-1993, 5 supervised single doses of ivermectin were
      given to inhabitants aged > or = 3 years in a Polynesian district: the first 3
      treatments were with 100 micrograms/kg and the 2 latter with 400 micrograms/kg.
      At each treatment, about 97% of the eligible population (899) were treated and
      blood samples were collected just before treatment from 96% of the 613
      inhabitants aged > or = 15 years. Following the 5 successive treatments, adverse
      reactions were observed in, respectively, 23.8, 13, 6.2, 13.6 and 7.9% of the
      microfilariae (mf) carriers, and in less than 1% of amicrofilaraemic subjects.
      Neither the frequency nor the intensity of adverse reactions was significantly
      different between single doses of 100 micrograms/kg and 400 micrograms/kg.
      Although the geometric mean microfilaraemia (GMM) was reduced, the mf carrier
      prevalence remained unchanged before and after 3 mass treatments with 100
      micrograms/kg (21.4 and 20.7% respectively), and the mf recurrence rate 6 months
      after each dose of 100 micrograms/kg was roughly stable (respectively, 34.3%,
      21.6% and 31.2% of the initial GMM). In contrast, after one dose round of 400
      micrograms/kg, the mf carrier prevalence decreased significantly to 14.9% (P <
      10(-6)), and the mf recurrence rate dropped to 9.9% (P < 10(-3)) of the initial
      GMM. These results confirm the safety and the effectiveness of 400 micrograms/kg
      of ivermectin for lymphatic filariasis control.

PMID- 7570846
TI  - A randomized comparative study of fleroxacin and ceftriaxone in enteric fever.

PMID- 7570848
TI  - Serum antibody response to Opisthorchis viverrini antigen as a marker for
      opisthorchiasis-associated cholangiocarcinoma.
AB  - The liver flukes Opisthorchis viverrini and Clonorchis sinensis chronically
      infect over 30 million people in south-eastern Asia, resulting in significant
      morbidity and a predisposition to cholangiocarcinoma (CCA). Liver fluke
      associated CCA carries a poor prognosis, partly because it is often detected at a
      late and advanced stage. The development of improved diagnostic methods,
      particularly for early CCA, may improve chances of survival and cure.
      Accordingly, we explored the use of immunological responses to liver fluke
      antigens as a potential means of identifying individuals at high risk for liver
      fluke-associated CCA. Serum antibody responses to O. viverrini adult worm
      homogenate and metacercaria homogenate (MH) were studied using enzyme-linked
      immunosorbent and immunoblot assays in 65 infected residents of an
      opisthorchiasis-endemic area in Thailand. Antibody levels correlated with liver
      ultrasonography (U/S) findings, and immunoblot analysis revealed a 91/93 kDa MH
      doublet recognized only by sera of individuals with severe liver U/S findings,
      including CCA. These results suggest that serum antibody responses to liver fluke
      antigens may be useful in the identification of infected individuals who are at
      high risk for liver fluke-associated CCA.

PMID- 7570852
TI  - A modified artificial membrane feeding method for the study of the transmission
      dynamics of leishmaniasis.

PMID- 7570847
TI  - Interferon-gamma production by peripheral blood mononuclear cells from residents
      of an area endemic for Schistosoma mansoni.
AB  - During human schistosomiasis host responses to antigens of various parasite life
      cycle stages may contribute to whether the severe, hepatosplenic state develops
      or the patient remains relatively asymptomatic throughout infection, and may play
      a role in resistance. This study evaluated production of interferon gamma (IFN
      gamma) in vitro by schistosome antigen-stimulated peripheral blood mononuclear
      cells (PBMCs) from asymptomatic patients, and by PBMCs from apparently
      uninfected, untreated persons living in areas endemic for Schistosoma mansoni
      ('endemic normals'). IFN-gamma production parallels PBMC proliferation in that
      schistosomal egg antigens stimulate patent patients' cells poorly, but strongly
      stimulate PBMCs from 'endemic normals'. This is proportionally true for antigens
      from adult worms and cercariae. Although asymptomatic patent patients' cells
      produced little or no IFN-gamma in response to the 3 schistosomal antigenic
      extracts, their PBMCs, and PBMCs from 'endemic normals', produced expected
      amounts of IFN-gamma when exposed to phytohaemagglutinin. This implies that
      persons with patent infections have schistosome antigen-specific defects in their
      ability to respond to IFN-gamma production that are not exhibited by putatively
      resistant 'endemic normals'.

PMID- 7570851
TI  - Importance of acidic intracellular compartments in the lysis of Trypanosoma
      brucei brucei by normal human serum.

PMID- 7570850
TI  - Schistosomiasis in the Republic of Sao Tome and Principe: characterization of
      Schistosoma intercalatum.
AB  - This paper reports the morphological and biochemical characterization of the
      species of Schistosoma infecting humans in the Republic of Sao Tome and Principe.
      The eggs are typical in shape and size of S. intercalatum, measuring on average
      between 174.5 microns and 189.1 microns. The eggs are voided in the faeces and
      not the urine of infected people. The parasite experimentally develops in several
      different species of Bulinus belonging to the B. forskalii group, including B.
      forskalii, with a minimum prepatent period of 25 d, and also in snails of the B.
      reticulatus group (B. wrighti); it is incompatible with snails of the B.
      africanus and B. truncatus/B. tropicus complex. A survey of 5 different habitats
      at intervals of 2 weeks over a period of one year showed that populations of B.
      forskalii increased during the dry period of June, July and August in 1988, and
      in 3 of the habitats snails were present throughout the year. Hence transmission
      may take place in these habitats throughout the year. Preliminary evidence
      suggests that water velocity is a limiting factor confining Bulinus to the north
      east of the island where the terrain is less mountainous. Development of
      schistosomes from Sao Tome was followed in experimentally infected hamsters. The
      cross-over point (the point at which the paired male and female worms are of the
      same average length) occurred at about 49 d after infection: eggs were first seen
      in the uteri of the female worms 48 d after infection. The parasite from Sao Tome
      developed in sheep and produced viable eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570853
TI  - Culturing Plasmodium falciparum from finger-prick samples of infected blood.

PMID- 7570854
TI  - Infectivity of dogs naturally infected with Leishmania infantum to colonized
      Phlebotomus perniciosus.
AB  - A study was carried out on the infectivity to sandflies of 16 dogs naturally
      parasitized by Leishmania infantum. All dogs were seropositive and the parasite
      had been isolated from all except one. They were divided into 3 clinical groups:
      5 asymptomatic, 4 oligosymptomatic, and 7 polysymptomatic dogs. The dogs were
      exposed to female Phlebotomus perniciosus from a local colony and 7 d later the
      fed females were dissected in order to determine their rate of infection. There
      was wide variability of the percentage of fed and infected sandflies within each
      clinical group of dogs, with no significant difference between the 3 groups; the
      infectivity to sandflies was independent of the extent of symptoms in the dogs.

PMID- 7570856
TI  - Onchocerciasis in Rwanda?

PMID- 7570855
TI  - Misdiagnosis of cerebral malaria in adolescents and adults in an endemic area.

PMID- 7570857
TI  - Recent developments in cestode research.

PMID- 7570858
TI  - Royal Society of Tropical Medicine and Hygiene Meeting at Manson House, London,
      16 February 1995. Aspects of Helicobacter pylori infection in the developing and
      developed world. Helicobacter pylori infection, nutrition and growth of West
      African infants.
AB  - Helicobacter pylori is probably the commonest bacterial infection of humankind.
      In adults, colonization of the stomach is associated with chronic gastritis and
      duodenal ulcer disease. However, children in the developing world acquire H.
      pylori soon after birth, and there is evidence that it plays a part, through
      suppression of the gastric acid barrier, in the pathogenesis of the syndrome of
      diarrhoea, malnutrition and growth failure. Infants born of mothers who secrete
      milk with high levels of anti-H. pylori immunoglobulin A (IgA) antibody acquire
      the infection later than those born of mothers with low specific antibody levels.
      Enhancement of maternal breast milk anti-H. pylori IgA levels may protect infants
      from H. pylori infection during the vulnerable weaning period when many are
      susceptible to enteric infections, leading to recurrent diarrhoea and adverse
      consequences on nutrition and growth.

PMID- 7570859
TI  - Failure of passive zooprophylaxis: cattle ownership in Pakistan is associated
      with a higher prevalence of malaria.
AB  - To examine the possibility that domestic cattle kept in house courtyards might
      protect occupants against malaria through zooprophylaxis, parasite prevalence
      surveys were conducted of schoolchildren in Pakistani and Afghan refugee villages
      and analysed according to whether each child's family kept cattle. Parasite
      prevalence (15.2%) was significantly greater among children of families which
      kept cattle than among those which did not (9.5%). Comparison of prevalence
      between different villages revealed a positive correlation between parasite rates
      and the proportion of families owning cattle. The latter finding supports the
      prediction of the Sota-Mogi theoretical model that domestic animals can enhance
      rather than reduce malaria transmission when vectors are zoophilic, the infection
      rate low, and the human:cattle ratio high. All these conditions applied in the
      study area.

PMID- 7570861
TI  - Estimating sporozoite rates by examining pooled samples of mosquitoes.
AB  - Pooling sampled mosquitoes for sporozoite detection by immunoassays is an
      efficient and economic approach in situations of very low vector infectivity. In
      the present study a strategy was proposed to estimate sporozoite rates using this
      approach. For this purpose there should be only one infected mosquito in any
      positive pool, so that the number of positive pools examined is an approximation
      of the number of infected mosquitoes in sample collections. The rationale
      underlying the strategy is to specify the maximal pool sizes for the given
      sporozoite rates so that it is reasonable to assert there is no more than one
      infected mosquito in any positive pool. A statistical model was developed to
      calculate the maximal pool sizes for various guessed sporozoite rates. The
      results showed that maximal pool size declined non-linearly with increases in the
      given sporozoite rates. With a guessed sporozoite rate < 1% as many as 35
      mosquitoes could be pooled for sporozoite determination.

PMID- 7570860
TI  - Recruitment to a trial of tuberculosis preventive therapy from a voluntary HIV
      testing centre in Lusaka: relevance to implementation.
AB  - To determine the number of clients attending for voluntary human immunodeficiency
      virus (HIV) testing who are able to enter a trial of preventive therapy for
      tuberculosis, and the factors that determine who receives therapy, we studied 475
      consecutive people attending for an HIV test at Lusaka's first voluntary HIV
      testing centre and the preventive therapy study clinic at the University Teaching
      Hospital, Lusaka, Zambia. Semi-structured interviews were conducted by
      counsellors and collated with recruitment data from the trial. Two hundred and
      twenty-five people were seropositive, of whom 201 returned to collect their
      results; 77 (38%) of these (16% of the total number screened) entered the trial.
      Reasons for not entering the trial included exclusion by trial protocol (30),
      including 18 who had active tuberculosis; psychological adjustment to a positive
      result (27); death (6); worries about confidentiality (3); the experimental
      nature of the trial (12); attitudes of staff in the hospital (5); and cost of
      transport (7). Targeting preventive therapy at those who are already choosing to
      be tested for HIV seems appropriate and may be cost-effective. Although visiting
      a hospital may deter some people, the prevalence of active tuberculosis among
      this group emphasized the importance of arranging adequate screening facilities.

PMID- 7570863
TI  - Diversity among Leishmania isolates from the Sudan: isoenzyme homogeneity of L.
      donovani versus heterogeneity of L. major.
AB  - Leishmania isolates from patients in the Sudan suffering from either visceral or
      cutaneous leishmaniasis were characterized using a battery of 12 enzymes.
      Aspartate aminotransferase separated the L. donovani isolates into 2 distinct
      zymodemes, but the overall results showed no significant geographical variation
      among L. donovani isolates. In contrast, the isolates of L. major were
      polymorphic, exhibiting differences in nucleoside hydrolase, 6-phosphogluconate
      dehydrogenase, superoxide dismutase, esterase, mannose phosphate isomerase, and
      aspartate aminotransferase, resulting in the description of 4 new enzymatic
      variants.

PMID- 7570865
TI  - French Guiana must be recognized as an endemic area of Leishmania (Viannia)
      braziliensis in South America.

PMID- 7570864
TI  - The characterization of Leishmania from patients with lymphadenopathy in Shiraz,
      Iran.
AB  - Leishmania were cultured from enlarged lymph nodes of 6 of 18 patients with
      localized lymphadenitis and no other sign or symptom of leishmaniasis in Shiraz,
      Iran. The organisms failed to produce visible lesions when injected intradermally
      or intraperitoneally into Swiss outbred white or Balb/c mice. Golden hamsters
      similarly injected appeared well 16 weeks later, but histological examination of
      their spleens and livers revealed a few amastigotes in sections of the liver of
      one. Lectin agglutination profiles of promastigotes cultured from 2 of the
      patients were identical with those obtained with the World Health Organization
      reference strain of L. tropica (MHOM/SU/74/K27). Isoenzyme characterization of
      one of the isolates showed it to be L. tropica zymodeme LON18.

PMID- 7570862
TI  - Visceral leishmaniasis in Somalia: prevalence of markers of infection and disease
      manifestations in a village in an endemic area.
AB  - Prevalence and disease manifestations of visceral leishmaniasis (VL) were studied
      in a Somali village in an area which has long been known to be endemic for VL.
      Demographic data were collected from 102 households, comprising 438 inhabitants.
      Clinical examination was performed of 306 individuals, 72% of the 426 eligible
      persons. Of these, 276 (90%) agreed to give blood and 246 (80%) to be skin tested
      with leishmanin. Leishmanin reactions were positive; in 26% anti-Leishmania
      antibodies were detected in 11%, and splenomegaly was recorded in 14% (23% of
      those who were seropositive). Malaria was hypoendemic and therefore unlikely to
      be responsible for more than 10% of the cases with splenomegaly. Three of the
      seropositive villagers with splenomegaly complained of feeling ill. The remaining
      91 sero- and/or leishmanin-positive individuals had no complaint regarding their
      health and had not experienced any long period of illness. There was a slight
      over-representation of males in the group of sero- and/or leishmanin-positive
      villagers, possibly due to a gender-associated difference in exposure to the
      parasite. Among the patients with clinical VL treated at Mogadishu hospitals
      during 1989 and 1990, the male/female ratio was 3.3:1, which may indicate a
      selection of male patients for hospital care. Most patients were < or = 15 years
      old, suggesting that the highest risk of becoming clinically ill was among
      children.

PMID- 7570866
TI  - Bancroftian filariasis in two urban areas of Recife, Brazil: pre-control
      observations on infection and disease.
AB  - Bancroftian filariasis is a major public health problem in the city of Recife in
      north-eastern Brazil. In some of its urban areas microfilaraemia prevalence
      reaches 14%. This study describes epidemiological characteristics, infection and
      disease, in 2 urban areas, Coque and Mustardinha, before control measures were
      applied. The parasitological survey was performed by a 'door-to-door' census
      covering 5563 subjects, aged between 5 and 65 years. Microfilaraemia was detected
      by the thick drop technique, using 45 microL of peripheral blood collected
      between 20:00 and 24:00. In both areas the prevalence of microfilaraemia was 10%,
      and males had higher prevalences of infection and disease than females. The
      prevalence of microfilaraemia was higher in the 15-24 and 25-34 years age groups
      in both sexes. Most microfilaria (mf) carriers (72.1% in Coque and 79.7% in
      Mustadrinha) had mf densities < 100/60 microL of blood. Females of reproductive
      age had significantly lower mf densities than males. The overall disease
      prevalence in both areas was 6.3%. Amongst the subjects who presented with
      chronic disease 15.7% were microfilaraemic. Chronic disease prevalence increased
      from 1.4% in the 5-14 years age group to 11.3% in the oldest age group. The most
      frequent clinical manifestation was hydrocele (5.4%), followed by lymphoedema
      (1.8%). The epidemiological pattern of filariasis in the populations studied was
      marked by high prevalence of microfilaraemia, low mf density, and relatively low
      prevalence of filarial disease considering the level of endemicity.

PMID- 7570867
TI  - Serological evidence for the presence of toxocariasis in the Turkana District of
      Kenya.

PMID- 7570868
TI  - Evidence for larval hypobiosis in Australian strains of Ancylostoma duodenale.

PMID- 7570869
TI  - Low prevalence of hepatitis C virus infection in Lusaka, Zambia.

PMID- 7570871
TI  - Prevalence of leptospiral infections in humans in Cordillera Province, Bolivia.

PMID- 7570870
TI  - Distribution and persistence of Mycobacterium leprae nasal carriage among a
      population in which leprosy is endemic in Indonesia.
AB  - In order to understand better the relationship among Mycobacterium leprae, its
      transmission and the human host or the chain of infection which may lead to the
      development of leprosy, we performed a population survey in which nasal carriage
      of M. leprae was determined by a specific polymerase chain reaction (PCR), 2
      years after an earlier survey in the same population. 1923 persons were
      registered, 1171 were clinically examined for signs of leprosy, and 418 were
      tested by PCR. The detection rate of leprosy in the study area had not changed
      significantly during the 2 years' observation period since the introduction of
      multi-drug therapy, i.e. 6/1000 compared to 7.7/1000 2 years before. Of 6 newly
      detected cases, 5 were diagnosed as having paucibacillary leprosy. The presence
      of M. leprae could be demonstrated by PCR in 2.9% (12/418) of the persons. PCR
      positivity was not persistent over the 2 years. All the PCR positive persons
      identified in the first survey were negative in the second, indicating that M.
      leprae nasal carriage is transient. As in the previous survey, we found evidence
      for widespread M. leprae nasal carriage as determined by PCR among the general
      population in an area in which leprosy is endemic. In addition, our data
      indicated that PCR positivity can occur in certain clusters in the community.
      This clustering seems to be time-dependent, not necessarily related to the
      presence of patients.

PMID- 7570872
TI  - Does Lyme disease (or an analogous disease) exist in Mali, West Africa?

PMID- 7570877
TI  - Human cutaneous leishmaniasis caused by Leishmania donovani sensu stricto in
      Yemen.

PMID- 7570875
TI  - Comparison of two media for the isolation and short-term culture of Entamoeba
      histolytica and E. dispar.

PMID- 7570873
TI  - Isolation of Trypanosoma brucei gambiense from northern Uganda: evaluation of the
      kit for in vitro isolation (KIVI) in an epidemic focus.
AB  - 867 individuals from 3 sites near the town of Adjumani in the East Moyo region of
      north-west Uganda were investigated clinically and serologically for evidence of
      current trypanosome infections. Blood samples were taken from 94 persons with a
      positive card agglutination test for trypanosomiasis (CATT) and clinical suspects
      and inoculated into the kit for in vitro isolation of Trypanosoma brucei
      gambiense (KIVI). Amongst this group, 30 parasitaemic individuals were identified
      by microhaematocrit centrifugation and the quantitative buffy coat technique
      (QBC). Only 80% of these isolates, and one isolate from an aparasitaemic
      individual, grew in culture. The success or failure of cultures from parasitaemic
      patients was unrelated to the size of the trypanosome inoculum. The implications
      of these results and possible reasons for the failure of KIVI are discussed.

PMID- 7570874
TI  - Leishmania donovani: titration of antibodies to the fucose-mannose ligand as an
      aid in diagnosis and prognosis of visceral leishmaniasis.
AB  - The fucose-mannose ligand (FML) is a complex glycoprotein fraction present on
      promastigotes and amastigotes of Leishmania donovani. It participates in parasite
      interaction with host macrophages in a species-specific pattern. We have tested
      its use in immunodiagnosis of visceral leishmaniasis (VL) in a recent outbreak in
      Rio Grande do Norte, north-east Brazil. Enzyme-linked immunosorbent assay (ELISA)
      of low concentrations of FML in 462 sera showed 100% sensitivity and 96%
      specificity. The FML-ELISA identified patients with overt VL (P < 0.001, compared
      to normal sera). It could also identify inhabitants of the endemic area who had
      incipient or subclinical infection with potentially severe clinical disease: more
      than 20% of apparently healthy subjects with a positive ELISA for FML developed
      overt VL during the following 10 months. FML-ELISA reactivity decreased in all
      patients during treatment, and became negative after parasitological cure. No
      cross-reaction was observed in patients infected with other Leishmania species,
      nor in those with Chagas disease. Determination of antibody response to FML may
      be useful in diagnosis of VL and in identifying patients without overt disease
      but with a high risk of developing severe VL.

PMID- 7570876
TI  - Comparison of the circulating anodic antigen detection assay and urine filtration
      to diagnose Schistosoma haematobium infections in Mali.
AB  - The applicability of a circulating Schistosoma antigen detection assay for
      determining rates of infection and efficacy of chemotherapy was evaluated in
      Mali. Urine egg counts were compared to circulating anodic antigen enzyme-linked
      immunosorbent assay (CAA-ELISA) titres in serum, before and 6 weeks after
      treatment with a single dose of praziquantel (40 mg/kg), in 2 villages in Dogon
      Country, an area endemic for S. haematobium, the predominant schistosome
      infection in Mali. In Kassa, a village with a moderate prevalence of infection,
      the serological prevalence (48%) was significantly higher than the
      parasitological prevalence (31%). In Boro, a village with high parasitological
      prevalence (76%), no difference was observed between the results of both methods
      (prevalence by CAA-ELISA was 75%). Cure rates estimated by CAA-ELISA were lower
      than those determined parasitologically, suggesting that cure rates are
      overestimated by egg counting. The sensitivity of the CAA-ELISA was 78%. In both
      villages, before treatment, a positive correlation was found between the number
      of eggs in urine and serum CAA titres. It is concluded that, although further
      simplification and improvement of the sensitivity of the assay is needed, in its
      present ELISA format the antigen detection assay is useful for monitoring
      sentinel populations. Furthermore, the serum CAA assay performed adequately in a
      public health laboratory within an endemic country.

PMID- 7570879
TI  - Isolation of Leishmania from a newborn puppy.

PMID- 7570880
TI  - Transmission of Entamoeba histolytica within a family complex.
AB  - A limited outbreak of symptomatic intestinal and extraintestinal amoebiasis
      within a family complex is described. The infection was almost certainly
      transmitted by a Philippino housemaid, who was an asymptomatic carrier of
      Entamoeba histolytica infection acquired in her native country. Starch-gel
      electrophoresis showed isoenzyme patterns characteristic of pathogenic zymodeme
      XIX in all the amoebic isolates.

PMID- 7570878
TI  - Human immunodeficiency virus and recurrence of cutaneous leishmaniasis long after
      healed localized cutaneous leishmaniasis due to Leishmania aethiopica.

PMID- 7570881
TI  - Chronic pulmonary disorders, including tropical pulmonary eosinophilia, in
      villages with endemic lymphatic filariasis in Tanga region and in Tanga town,
      Tanzania.
AB  - To investigate the occurrence of tropical pulmonary eosinophilia (TPE), studies
      were undertaken in 3 villages with endemic lymphatic filariasis in the coastal
      area of Tanga Region, Tanzania, and in the outpatient clinic of Bombo Regional
      Hospital in Tanga town; 73 persons from the villages and 104 from the outpatient
      clinic with a history of lung disease suggestive of TPE were included in the
      study. Following clinical examination, lung function tests and chest X-rays were
      performed. Total leucocyte and eosinophil counts were recorded. Parasitological
      examinations included blood for microfilariae and stools and urine for eggs of
      intestinal helminths and Schistosoma haematobium respectively. Total
      immunoglobulin (Ig) E and specific antifilarial IgE and IgG4 were measured.
      Suspected TPE cases were treated with diethylcarbamazine, 6 mg/kg for 12 d, and
      were followed up 14, 90 and 360 d after treatment. Three persons fulfilled the
      criteria for TPE. Their response to treatment was marked, with clinical
      improvement, reduction in eosinophil count and reduced titres of specific
      antifilarial IgE and IgG4. Although TPE is present in Wuchereria bancrofti
      endemic areas of East Africa, it appears to be rare, as in other endemic areas.

PMID- 7570883
TI  - Liver pathology in rural south-west Cameroon.
AB  - In a prospective study, 102 hospital patients with liver disease were evaluated
      in West Cameroon, Africa. Blood donors, pregnant women and patients without liver
      disease served as controls. A total of 757 individuals were tested for markers of
      hepatitis A, B, C and D and for immunological markers (autoantibodies,
      procollagen III, alpha-foetoprotein, CA50 antigen, alpha-1-antitrypsin and
      antibodies to human immunodeficiency virus types 1 and 2). One-third of the liver
      disease patients had focal lesions on ultrasound examination. Histologically, 20
      cases of cirrhosis, 14 cases of chronic hepatitis, 15 hepatocellular carcinomas
      and 17 cases of acute hepatitis were detected. All hepatic patients and virtually
      all controls had had a previous hepatitis A virus infection. Over 85% of adult
      patients and controls had at least one marker of hepatitis B virus infection.
      Over 30% of patients with liver disease had markers of possible hepatitis B virus
      replication. Antihepatitis C virus antibody was present in 18% of hepatic
      patients and in 6% of controls. Hepatitis C virus infection seems to play an
      important role in the development of chronic liver pathology; 40% of cirrhotic
      patients had a combined hepatitis B and C virus infection. Serum autoantibodies
      were frequently found and were not correlated with the presence of autoimmune
      liver disease.

PMID- 7570882
TI  - Cryptococcal meningitis in Cairo, Egypt: report of five cases.

PMID- 7570884
TI  - Electrophysiological findings in patients envenomed following the bite of a
      Papuan taipan (Oxyuranus scutellatus canni).
AB  - Electrophysiological studies were done on patients with systemic neurotoxicity
      following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Evoked
      compound muscle action potentials decreased and increased in tandem with clinical
      deterioration and recovery. Nerve conduction velocities did not change in
      envenomed patients and were consistent with control studies. Repetitive nerve
      stimulation studies showed decremental responses in envenomed patients with post
      tetanic potentiation followed by post-tetanic exhaustion. The findings are
      consistent with studies in vitro which suggested that the major action of
      neurotoxins in Australian taipan venom is at the synapse. The observation that
      electrophysiological data correlate closely with the clinical condition of the
      patient has potential application in the assessment of interventions in the
      management of snake bite victims.

PMID- 7570885
TI  - Intrarectal Quinimax (an association of Cinchona alkaloids) for the treatment of
      Plasmodium falciparum malaria in children in Niger: efficacy and
      pharmacokinetics.
AB  - In an attempt to avoid the complications associated with intramuscular quinine
      administration, we assessed the intrarectal route. Sixty-six children aged from 2
      to 10 years with Plasmodium falciparum malaria were included in the study, which
      took place in Niamey, Niger. Fifty-five children were given 20 mg/kg of the
      diluted injectable form of Quinimax (a quinine, quinidine, cinchonine,
      cinchonidine association) intrarectally. A further 11 children with malaria were
      treated with 12.5 mg/kg of the same Quinimax solution by the intramuscular route.
      All the children were treated twice a day for 3 d. Blood samples were drawn from
      20 children (15 treated intrarectally and 5 intramuscularly) for a kinetic study.
      Both modes of administration were well tolerated. Mean fever clearance times (+/-
      standard errors) were 48.6 +/- 2.7 h and 35.9 +/- 2.2 h in the intrarectal and
      intramuscular groups, respectively (P = 0.05). Mean parasite clearance times (+/-
      standard errors) and mean times to achieve 50% reduction in parasitaemia (+/-
      standard errors) were similar after intrarectal (46.5 +/- 5.7 h and 7.8 +/- 0.9 h
      respectively) and intramuscular administration (27.4 +/- 3.6 h and 8.7 +/- 1.7 h,
      respectively). Tmax. after intrarectal administration (2.7 +/- 0.4 h) did not
      differ significantly from the value after intramuscular administration (1.1 +/-
      0.6 h), but Cmax. and the area under the concentration-time curve from 0 to 48 h
      were lower (4.9 +/- 0.6 mg/L and 230.0 +/- 9.6 mg/L.h, respectively) than after
      intramuscular administration (9.1 +/- 1.2 mg/L and 356.0 +/- 4.2 mg/L.h,
      respectively) (P < 0.001). Compared to the intramuscular route, intrarectal
      Quinimax bioavailability was 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7570889
TI  - Mefloquine-induced grand mal seizure during malaria chemoprophylaxis in a non
      epileptic subject.

PMID- 7570887
TI  - Clinical response and susceptibility in vitro of Plasmodium vivax to the standard
      regimen of chloroquine in Thailand.
AB  - The clinical effectiveness of the standard regimen of chloroquine (CQ) (a total
      dose of 1500 mg, given over 48 h at 0, 6, 24 and 48 h) for the treatment of
      Plasmodium vivax malaria in Thailand was investigated in 57 patients in an
      endemic area of Thailand (Chantaburi Province, eastern Thailand). For radical
      treatment, an additional course of a tissue schizontocidal agent, primaquine, was
      given following the complete course of CQ. With this regimen, satisfactory whole
      blood concentration-time profiles of CQ and its major metabolite
      desethylchloroquine (DECQ) were achieved. Mean whole blood levels of CQ and DECQ
      always much exceeded the reported therapeutic level of CQ (90 ng/mL) during the
      first 7 d of treatment. All patients responded well to the treatment; in most
      cases, complete and rapid clearance of parasitaemia was observed within the first
      48 h. No reappearance of the parasitaemia was detected in peripheral blood films
      of any patient within 14 d of the evaluation period. In 6 patients, however,
      reappearance of P. vivax parasitaemia was observed after 30 d; 2 of them had not
      completed the course of primaquine. There was no difference in whole blood
      concentrations of CQ and DECQ, admission parasitaemia, susceptibility of the
      isolates to chloroquine in vitro, and parasite clearance time between patients
      with or without reappearance of parasitaemia. A prominent trend of deteriorating
      sensitivity of the parasite to the drug was, however, suggested.

PMID- 7570888
TI  - Cardiac complications of halofantrine: a prospective study of 20 patients.
AB  - Halofantrine, increasingly used for treatment of Plasmodium falciparum malaria,
      is a normally well-tolerated amino-alcohol with very few side-effects, but
      torsades de pointes ventricular tachycardia due to halofantrine has been reported
      in a few patients with a congenital long QT interval (Romano-Ward syndrome). We
      performed a prospective study of the cardiac effect of halofantrine in 20
      patients with 48 h ambulatory electrocardiographic (ECG) monitoring; the
      halofantrine levels in their serum were also determined. Minimal ECG changes were
      noted, with lengthening of the QT interval without clinical symptoms. This effect
      was dose-dependent and can be very severe in cases of pre-existing cardiopathy;
      it also occurs in patients without any pre-existing cardiopathy. In order to
      reduce the likelihood of such incidents, which are admittedly rare, we suggest
      performing electrocardiography on all patients before initiating treatment with
      halofantrine.

PMID- 7570886
TI  - Antimalarial drug response of Plasmodium falciparum from Zaria, Nigeria.
AB  - The sensitivity of Zaria strains of Plasmodium falciparum to chloroquine,
      mefloquine, quinine and sulphadoxine/pyrimethamine was investigated 5 years after
      the appearance of in vivo/in vitro chloroquine resistance in urban Zaria.
      Infections in 36/43 children (83.7%) treated with chloroquine were sensitive
      while those in 7 (16.3%) were resistant. 8/13 isolates cultured (61.5%) were
      sensitive in vitro to chloroquine and 5 (38.5%) were resistant. Of the cultured
      isolates, 13/13 (100%), 12/13 (92.3%) and 5/7 (71.4%) showed mefloquine, quinine
      and sulphadoxine/pyrimethamine sensitivity, respectively. The results confirmed
      chloroquine and sulphadoxine/pyrimethamine resistance in urban Zaria and revealed
      emerging quinine resistance. Resistance to chloroquine and
      sulphadoxine/pyrimethamine is at RI level and chloroquine should continue to be
      the first-line drug for the treatment and prevention of P. falciparum infection
      in the Zaria area of northern Nigeria. We suggest that, while quinine serves as
      second-line drug, mefloquine should be reserved for infections resistant to
      chloroquine, quinine and sulphadoxine/pyrimethamine.

PMID- 7570892
TI  - Treatment with allopurinol and itraconazole changes lytic activity in patients
      with chronic, low grade Trypanosoma cruzi infection.

PMID- 7570890
TI  - Artemether treatment of sulfadoxine/pyrimethamine-resistant Plasmodium falciparum
      malaria in children.

PMID- 7570893
TI  - Apparently successful treatment of two cases of post kala-azar dermal
      leishmaniasis with liposomal amphotericin B.

PMID- 7570891
TI  - Assessment of the association between three pfmdr1 point mutations and
      chloroquine resistance in vitro of Malaysian Plasmodium falciparum isolates.

PMID- 7570894
TI  - Direct assessment of the adulticidal efficacy of a single dose of ivermectin in
      bancroftian filariasis.
AB  - Although the potent microfilaricidal activity of ivermectin is well established,
      its efficacy against adult Wuchereria bancrofti is unknown. We used longitudinal
      ultrasound examinations for periods of 3-9 months to assess directly the
      macrofilaricidal effect of a single 400 micrograms/kg dose of ivermectin in 15
      men from Recife, Brazil who were infected with W. bancrofti. Before treatment,
      microfilarial densities ranged from 3 to 3098 microfilariae per mL of blood, and
      movements characteristic of the living adult worm (the 'filaria dance sign') were
      observed by ultrasound examination of the scrotal lymphatic vessels in all 15
      men. Following treatment, microfilarial density was markedly reduced in all men,
      but the filaria dance sign remained unchanged in both location and pattern. Eight
      months after treatment, a dilated lymphatic vessel was surgically removed from
      one patient at the site of the filaria dance sign, and 3 intact adult worms were
      released. When given as a single 400 micrograms/kg dose, ivermectin had no
      observable effect on adult W. bancrofti. Therefore, prolonged suppression of
      microfilaraemia following treatment with ivermectin cannot be explained by a
      macrofilaricidal effect of the drug. Ultrasound is a valuable new tool for
      directly and rapidly assessing the macrofilaricidal efficacy of antifilarial
      drugs in lymphatic filariasis.

PMID- 7570896
TI  - Use of a recombinant Trypanosoma cruzi protein antigen to monitor cure of Chagas
      disease.

PMID- 7570897
TI  - Aminopropeptide of human procollagen type I: a marker for the identification of
      blood from children in the mosquito blood meal.
AB  - A capture enzyme-linked immunosorbent assay (ELISA) to distinguish between blood
      from children and adults in the mosquito blood meal was examined using the alpha
      1 chain of the aminopropeptide of human procollagen type I (PINP) as antigenic
      marker. Rabbit anti-human PINP (alpha 1) antibody was used as catching antibody,
      and either normal serum from 288 African and 58 Caucasian children and adults, or
      blood meals from 93 fed Aedes aegypti, were examined. PINP in excess of 40
      optical density units (ODU) was detected in all children aged 0-13 years, whereas
      adults aged 21-77 years had PINP levels less than 25 ODU. In the transitional age
      group (14-20 years), the PINP levels ranged from 1 to 166 ODU. The PINP levels in
      95% of the mosquito blood meals obtained from children exceeded the control
      levels, using 13 ODU as a cut-off value, whereas none of the blood meals from
      adults exceeded 13 ODU. The PINP levels in the mosquito blood meals were constant
      1 and 8 h after ingestion, but they had decreased significantly after 16-19 h.
      Our data suggest that the test can be used to identify host preferences in
      studies of mosquitoes collected within 16 h after the blood meal. A field
      evaluation is necessary to determine the potential of the antigenic marker PINP
      as a tool in the identification of mosquito host preference.

PMID- 7570895
TI  - Failure of 3,4-diaminopyridine and edrophonium to produce significant clinical
      benefit in neurotoxicity following the bite of Papuan taipan (Oxyuranus
      scutellatus canni).
AB  - Progressive systemic neurotoxicity is a common feature in patients envenomed
      following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Respiratory
      paralysis, which commonly results, accounts for considerable morbidity and
      mortality. Established neurotoxicity does not respond to antivenom. In this
      study, a combination of clinical and electrophysiological variables was used to
      assess the effect of edrophonium and 3,4-diaminopyridine in patients with
      significant neurotoxicity. Both drugs produced minor electrophysiological and
      clinical changes in envenomed patients. This effect was maximal when the 2 drugs
      were used in combination, but was insufficient to be of significant clinical
      benefit. Neither drug can be recommended for use in the management of Papuan
      taipan bite.

PMID- 7570898
TI  - Cluster randomization trials in tropical medicine: a case study.
AB  - Field trials in tropical medicine are often designed so that intact social units
      (e.g., families, schools, communities) rather than independent individuals are
      randomized to an intervention group. Reasons are diverse, but include
      administrative convenience, a desire to reduce the effect of treatment
      contamination, and the need to avoid ethical issues that might otherwise arise.
      Dependencies among cluster members typical of such designs must be considered
      when determining sample size and analysing the resulting data. Failure to do so
      can result in false conclusions that the treatment is effective. The purpose of
      this paper is to compare different methods which can be used to construct tests
      of the effect of treatment when outcomes are binary (e.g., infected/uninfected).
      The discussion will be illustrated using data from a trial which randomly
      assigned families to either a control group or a screening and treatment
      programme for imported intestinal parasites.

PMID- 7570899
TI  - Bizarre transmission of cysticercosis.

PMID- 7570900
TI  - Bizarre transmission of cysticercosis.

PMID- 7570901
TI  - Bizarre transmission of cysticercosis.

PMID- 7570903
TI  - Bizarre transmission of cysticercosis.

PMID- 7570902
TI  - Bizarre transmission of cysticercosis.

PMID- 7570904
TI  - Optimal regimens of parenteral quinine.

PMID- 7570905
TI  - Absence of Lyme borreliosis from Gauteng, South Africa.

PMID- 7570907
TI  - Multi-gallon blood donors: why do they give?

PMID- 7570908
TI  - The quantitative analysis of transfusion medicine.

PMID- 7570906
TI  - Did Joseph Conrad have loiasis?

PMID- 7570909
TI  - Collection and transfusion of blood and blood components in the United States,
      1992.
AB  - BACKGROUND: Studies were conducted to measure the state of the United States'
      national blood resource in 1992 and changes therein from 1989. STUDY DESIGN AND
      METHODS: With data supplied by the American Red Cross and the American
      Association of Blood Banks, as well as data from a stratified random-sample
      survey of 3350 non-American Association of Blood Banks hospitals, statistical
      methods were applied to estimate national blood activities in 1992. RESULTS: The
      total US blood supply in 1992 was 13,794,000 units, a decrease of 3.1 percent
      from 1989. Some 11,307,000 red cell units were transfused to 3,772,000 patients,
      an average of 3.0 units per transfused patient. Preoperative autologous blood
      deposits totaled 1,117,000 units, a 70-percent increase over 1989. Of this
      number, 566,000 units (50.7%) were transfused, 5,000 (4.4%) transferred to the
      allogeneic supply, and 546,000 (48.9%) discarded. Of 436,000 directed-donation
      units, 136,000 (31.2%) were transfused, 57,000 (13.1%) transferred to allogeneic
      supply, and 243,000 (55.7%) discarded. The total allogeneic blood supply,
      including imports, decreased by 7.4 percent from 1989, and allogeneic blood
      transfusions, including those to children, decreased by 8.6 percent. Over
      8,300,000 platelet units were transfused; of these, some 3,600,000 were apheresis
      platelets. In addition, 2,255,000 units of plasma and 939,000 units of
      cryoprecipitate were transfused. CONCLUSION: While the US blood supply was
      adequate for transfusion needs in 1992, blood collections and red cell
      transfusions had decreased substantially since 1989.

PMID- 7570910
TI  - Blood group A immunodeterminants on human red cells differ in biologic activity
      and sensitivity to alpha-N-acetylgalactosaminidase.
AB  - BACKGROUND: Epitopes of blood group A antigen can be enzymatically cleaved from
      red cells (RBCs), but the extent of cleavage required for normal survival in
      allogeneic blood transfusion recipients is unknown. Therefore, the cleavage rates
      were studied for A antigen epitope binding of 1) complement-activating anti-A, 2)
      Dolichos biflorus anti-A, lectin, and 3) hemagglutinating anti-A during
      incubation with a purified alpha-N-acetylgalactosaminidase, E.C. 3.2.1.49 (alpha
      GalNAc'ase). STUDY DESIGN AND METHODS: Suspensions of group A RBCs were incubated
      with alpha-GalNAc'ase. Cells were removed at intervals, washed, and tested for
      loss of binding by monoclonal, polyclonal, and complement-activating anti-A, D.
      biflorus anti-A1 lectin, and Ulex europaeus anti-H lectin. RESULTS: A epitopes
      binding D. biflorus lectin were highly susceptible to alpha-GalNAc'ase;
      simultaneously with their loss, binding with U. europaeus lectin emerged. Loss of
      complement-mediated hemolysis was slower. A epitopes binding hemagglutinating
      anti-A were most resistant. Cleavage of A epitopes from membrane
      glycosphingolipids with short oligosaccharide chains was similarly resistant.
      Rates of cleavage from A1 and A2 RBCs were similar. CONCLUSION: RBC epitopes of
      blood group A differ in susceptibility to cleavage and biologic reactivity, which
      suggests that subsets mediating important biologic functions exist on
      functionally and topographically distinct membrane glycoconjugates.

PMID- 7570911
TI  - Molecular basis of the K:6,-7 [Js(a+b-)] phenotype in the Kell blood group
      system.
AB  - BACKGROUND: The Kell blood group system consists of at least 21 antigens.
      KEL6(Jsa) is a low-incidence antigen that has an antithetical relationship with
      the high-incidence KEL7(Jsb) antigen. The molecular basis of KEL6 that appears in
      less than 1.0 percent of the general population, but in up to 19.5 percent of
      African Americans, was unknown. STUDY DESIGN AND METHODS: Nineteen exons of the
      Kell gene (KEL) were amplified by polymerase chain reaction (PCR) assays of
      genomic DNA obtained from individuals with K:6,-7 [Js(a+b-)] phenotype. The PCR
      products were sequenced. A comparison was made of the sequence of the PCR
      products and the sequence of K:-6,7, the common phenotype. RESULTS: KEL from
      individuals with the K:6,-7 phenotype had two base substitutions in exon 17. One
      was a missense mutation (T-to-C base substitution) at nucleotide (nt) 1910, which
      predicts an amino acid change from leucine to proline; the other was a silent
      substitution (A-to-C) at nt 2019. The T-to-C substitution eliminated a
      restriction site for Mnl I, whereas the A-to-G substitution eliminated a Dde I
      site. Analyses of exon 17 in seven unrelated persons with K:6,-7 phenotype by Mnl
      I and Dde I enzymes showed the expected presence of restriction fragment length
      polymorphisms. CONCLUSION: The base substitutions T-to-C at nt 1910 and A-to-G at
      nt 2019 are unique to KEL6. The predicted Leu-->Pro change may disrupt the alpha
      helical structure and thus form the epitope for KEL6.

PMID- 7570912
TI  - Multi-gallon blood donors: who are they?
AB  - BACKGROUND: Although vital to the nation's blood centers, multi-gallon blood
      donors have never been the focus of investigation. STUDY DESIGN AND METHODS: In
      the fall of 1994, questionnaires were sent to 500 individuals who had donated 5
      gallons or more and to 500 randomly selected donors. RESULTS: Multi-gallon donors
      reported that they received little recognition or support for their efforts and
      were not pressured by friends or family. One-third were not allowed time off from
      work to donate. One in five reported having a "bad experience" while donating.
      Donors who had family members or friends who had received blood donated a greater
      number of units than those who were not as close to blood recipients. CONCLUSION:
      Women and minorities are underrepresented among long-term donors. Further
      research is needed to learn what "captures" donors and helps them to develop the
      psychological commitment to continue to give, as well as why few multi-gallon
      donors talk about blood donation.

PMID- 7570913
TI  - Flow cytometric analysis in platelet crossmatching using a platelet suspension
      immunofluorescence test.
AB  - BACKGROUND: The sensitivity of flow cytometric measurement of platelet antibodies
      in a crossmatch technique was investigated. STUDY DESIGN AND METHODS: The
      corrected count increment after platelet transfusion was compared with the
      fluorescence ratio determined by flow cytometric measurement. RESULTS: When
      crossmatching was performed before transfusion(s) in alloimmunized patients, a
      fluorescence ratio < or = 1.7 was associated with satisfactory responses
      (corrected count increment > or = 7.5), and the predictive values for negative
      and positive crossmatch results were 94 and 87 percent, respectively. Analysis of
      antigen preservation during platelet storage with antibodies to HLA alpha-chain,
      HLA-B27, HPA-1a, and HPA-3a showed that platelets can be stored, refrigerated,
      for up to 4 weeks without significant loss of HLA class I and HPA-1a. There was a
      slight but continuous loss of HPA-3a upon storage. CONCLUSION: Flow cytometric
      measurement of fluorescence in the platelet suspension immunofluorescence test
      can be used for platelet crossmatching, with sensitivity and predictive values
      comparable to those of previously described techniques and with the advantage of
      automation.

PMID- 7570914
TI  - The collection and evaluation of peripheral blood progenitor cells sufficient for
      repetitive cycles of high-dose chemotherapy support.
AB  - BACKGROUND: The development of an optimized peripheral blood progenitor cell
      (PBPC) harvest protocol to provide support for repetitive chemotherapy cycles is
      described. STUDY DESIGN AND METHODS: PBPCs mobilized by cyclophosphamide plus
      granulocyte-colony-stimulating factor (G-CSF) were studied in 163 leukapheresis
      harvests from 26 lymphoma patients. Harvested cells were transfused with two
      chemotherapy cycles and with an autologous bone marrow transplant. Progenitor
      cell content was examined in the context of hematopoietic engraftment. RESULTS:
      Mobilization allowed the harvest of large numbers of PBPCs. Peak harvests tended
      to occur after the recovering white cell count exceeded 10 x 10(9) per L. CD34+
      lymphomononuclear cell (MNC) and colony-forming units-granulocyte-macrophage (CFU
      GM) counts correlated poorly, but both measures peaked within 24 hours of each
      other in 21 of 26 patients, which demonstrated PBPC mobilization. Engraftment of
      platelets (> 50 x 10(9)/L) and granulocytes (> 500 x 10(6)/L) was achieved in a
      median of 20.5 and 16 days, respectively. A minimum number of progenitors
      necessary to ensure engraftment could be derived. CONCLUSION: Cyclophosphamide
      and G-CSF allowed the harvest of sufficient PBPCs to support multiple rounds of
      chemotherapy. Harvest should commence when the recovery white cell count exceeds
      10 x 10(9) per L. PBPC harvest CD34+MNC counts are as useful as CFU-GM results in
      the assessment of PBPC content, and they may allow harvest protocols to be
      tailored to individual patients.

PMID- 7570915
TI  - Increased detection of hepatitis C virus infection in commercial plasma donors by
      a third-generation screening assay.
AB  - BACKGROUND: Routine screening of blood donations with second-generation hepatitis
      hepatitis C virus (HCV) assays has substantially reduced the occurrence of
      posttransfusion hepatitis. However, following the development of third-generation
      assays, several studies indicated that these assays may identify HCV-infected
      individuals who are not identified by second-generation assays. STUDY DESIGN AND
      METHODS: The sensitivity of a third-generation HCV enzyme-linked immunosorbent
      assay (ELISA-3) was compared with a second-generation ELISA (ELISA-2) in a side
      by-side study of 9936 commercial blood donors. ELISA-reactive specimens were
      subjected to supplemental analysis by third-generation recombinant immunoblot
      assay and polymerase chain reaction. RESULTS: ELISA-3 demonstrated greater
      sensitivity than ELISA-2, detecting 1 additional recombinant immunoblot assay
      positive specimen per 2000 tested. ELISA-3 also detected 1 additional HCV
      infectious polymerase chain reaction-positive unit among approximately 10,000
      units screened. CONCLUSION: The incremental sensitivity achieved with ELISA-3 can
      be expected to eliminate approximately 20 infectious donations per week among
      those made by commercial donors in the United States. In accordance with previous
      studies, most of the improved sensitivity of ELISA-3 derives from its increased
      detection of anti-c33c (NS3), rather than from the inclusion of HCV antigen NS5.

PMID- 7570916
TI  - Blood use in patients undergoing repeat coronary artery bypass graft procedures:
      multivariate analysis.
AB  - BACKGROUND: The prevailing clinical opinion is that patients undergoing repeat
      coronary artery bypass graft (CABG) operation require more blood transfusions
      than do patients undergoing primary CABG operation. To determine the extent of
      this increased demand and the variables responsible for it, the cases of 196
      patients who had undergone primary procedures and 65 patients who had had repeat
      procedures at the same institution were reviewed. STUDY DESIGN AND METHODS: To
      analyze the differences in transfusion requirements for these two groups, the
      following data were obtained: number of transfusions given between the time of
      surgery and the time of hospital discharge; preoperative hemoglobin (Hb),
      hematocrit (Hct), prothrombin time, and platelet count; Hb and Hct at hospital
      discharge; time the patient was on cardiopulmonary bypass; number and type of
      grafts; estimates of intraoperative blood loss; and chest-tube blood shed during
      the first 48 hours after surgery. RESULTS: The groups were comparable with
      respect to age, body weight, preoperative Hb and Hct, number of grafts, and
      aspirin exposure. Patients in the repeat group had 35-percent greater blood loss
      and required 75-percent more blood components than did the patients undergoing
      primary procedures. The mean number of blood components transfused per patient
      was as follows: red cells, 3.8 +/- 0.5 units in repeat patients and 2.2 +/- 0.2
      units in primary patients (p = 0.002); platelets, 2.9 +/- 0.9 vs. 1.1 +/- 0.2 (p
      = 0.043); fresh-frozen plasma, 1.6 +/- 0.4 vs. 0.8 +/- 0.1 (p = 0.044). Analysis
      of variables by regression method for repeat patients showed a predictive effect
      of blood loss (p < 0.0001), prolonged time on cardiopulmonary bypass (p <
      0.0001), preoperative Hb (p = 0.0003), and aspirin exposure (p = 0.0094) on red
      cell transfusion rate in repeat patients (R-square = 0.7778, Prob > f = 0.0001).
      CONCLUSION: Repeat CABG patients have higher transfusion rates. These findings
      may be attributed to the increased microvascular bleeding, prolonged time on
      cardiopulmonary bypass, lower preoperative Hb, and the use of preoperative
      antiplatelet medications.

PMID- 7570917
TI  - Elimination of potential mutagenicity in platelet concentrates that are virally
      inactivated with psoralens and ultraviolet A light.
AB  - BACKGROUND: For virus sterilization of platelet concentrates (PCs), treatment
      with aminomethyltrimethyl psoralen (AMT) and long-wavelength ultraviolet A light
      (UVA) has shown efficacy. It has been found that treatment with 50 micrograms per
      mL of AMT and 38 J per cm2 of UVA in the presence of 0.35-mM rutin efficiently
      kills viruses while maintaining platelet integrity. There is, however, concern
      about the mutagenic potential of psoralens and UVA (PUVA)-treated PCs. STUDY
      DESIGN AND METHODS: Adsorption of PUVA-treated PCs with a hydrophobic resin
      containing C18 as the ligand was used for AMT removal, which was quantitated by
      the use of radioactive AMT. PUVA-treated PCs, with and without C18 treatment,
      were examined for solution pH and platelet aggregation response to agonists. In
      addition, residual AMT activity was determined by AMT's virucidal activity or
      incorporation into cellular DNA upon a second UVA irradiation and by its
      mutagenic potential in the Ames test. RESULTS: After PUVA treatment of PCs,
      residual AMT retained virucidal and adduct-forming ability upon re-exposure to
      UVA, but activities were less than those observed originally. As has been found
      previously, AMT had mutagenic potential following incubation in the dark with rat
      liver S9 microsomal enzymes. The PUVA treatment reduced this potential by 90
      percent. C18 adsorption following PUVA treatment had no negative effect on
      platelet integrity and eliminated 50 percent of the added radioactive AMT. In
      addition, all detectable virucidal, nucleic acid-modifying, and mutagenic
      activities of AMT-treated PCs were removed by C18. CONCLUSION: These results
      suggest that hydrophobic resin adsorption of PUVA-treated PCs will conveniently
      remove functional psoralens and eliminates their mutagenic potential.

PMID- 7570918
TI  - Gene frequencies of the five major human platelet antigens in African American,
      white, and Korean populations.
AB  - BACKGROUND: The study of the immunogenetics of the human platelet antigens is
      important to the improvement of diagnosis and genetic counseling and to the
      development of screening programs for women at risk of having babies with
      neonatal alloimmune thrombocytopenia. Description of the immunogenetics of the
      human platelet antigens in some racial groups has been incomplete. STUDY DESIGN
      AND METHODS: A reverse dot blot technique employing polymerase chain reaction
      amplified genomic DNA was applied in genotyping the five major human platelet
      antigens in the following populations: 100 African American and 100 white women
      admitted to the obstetric unit at Johns Hopkins Hospital (Baltimore, MD) and 100
      inpatients at Yonsei University (Seoul, Korea). RESULTS: The gene frequencies of
      HPA-2b (Koa) and HPA-5b (Bra) in African Americans were twice those in whites
      (African Americans: 0.18 and 0.21, respectively; whites: 0.09 and 0.11,
      respectively). There is a very low gene frequency of the HPA-1b (PIA2) allele in
      Koreans (0.005). No significant differences were found in the gene frequencies of
      the human platelet antigens in whites in this series and those in published
      European studies. CONCLUSION: These studies indicate a higher potential risk for
      alloimmunization to HPA-2 (Ko) and HPA-5 (Br) antigens in African Americans than
      in whites. In addition, the low gene frequency of HPA-1b (PIA2) in African
      Americans and Koreans suggests that alloimmunization to HPA-1a (PIA1) would be
      very unusual in these populations. These data may provide the basis for planning
      neonatal alloimmune thrombocytopenia screening programs in certain ethnic
      populations.

PMID- 7570919
TI  - Frequency of human platelet antigens among blood donors in northeastern Thailand.
AB  - BACKGROUND: Platelet transfusions have been widely used in Thailand, but little
      is known about the phenotyping of human platelet antigens. STUDY DESIGN AND
      METHODS: Whole blood was collected from 483 blood donors for preparation of
      platelets. An improved mixed passive hemagglutination assay was used for this
      study. RESULTS: Frequencies demonstrated were 100 percent for HPA-1a (PlA1),
      15.94 percent for HPA-2b (Siba), 60.25 percent for HPA-3a (Baka), 98.76 percent
      for HPA-4a (Yukb), 1.86 percent for HPA-4b (Yuka), 5.38 percent for HPA-5b
      (Br(a)), and 97.72 percent for Naka. CONCLUSION: HPA-1a was found in 100 percent
      of Thais, which is the same frequency as in other Asian populations but somewhat
      different from that in whites (97.9%). Therefore, HPA-1a will not cause neonatal
      alloimmune thrombocytopenia or post-transfusion purpura in Thais. According to
      the frequencies of HPA-2b, HPA-3a, HPA-4a, HPA-4b, HPA-5b, and Naka antigens,
      they may induce neonatal alloimmune thrombocytopenia, posttransfusion purpura,
      and platelet refractoriness in Thais.

PMID- 7570920
TI  - Retrograde transmission of Proteus mirabilis during platelet transfusion and the
      use of arbitrarily primed polymerase chain reaction for bacteria typing in
      suspected cases of transfusion transmission of infection.
AB  - BACKGROUND: When bacteria are found, after a platelet transfusion, in the
      recipient's blood as well as in the platelet concentrate (PC), a causal
      relationship is normally suspected, with the PC as the causative agent. The other
      alternative, that the patient has bacteremia and contaminated the PC, is less
      well documented in the literature. CASE REPORT: Arbitrarily primed polymerase
      chain reaction (AP-PCR) was used for testing strains of Proteus mirabilis
      isolated from a patient's blood before and after a platelet transfusion and from
      the PC. Because of a febrile reaction after a platelet transfusion, bacterial
      culture was performed on the PC used, showing growth of P. mirabilis. The same
      species was found in the patient's blood after the transfusion. Posttransfusion
      sepsis caused by a contaminated PC was suspected, and anti-sepsis treatment was
      given to the recipient. Later, it became apparent that the patient had had
      bacteremia before the transfusion and that P. mirabilis was one of the species in
      the isolate. With AP-PCR, the identity of the three P. mirabilis isolates could
      be distinguished. CONCLUSION: AP-PCR is a useful technique for distinguishing the
      identity of bacterial isolates from patients and blood components. A patient with
      bacteremia can contaminate a PC in conjunction with a platelet transfusion. With
      AP-PCR, the PC could be ruled out as the cause of the posttransfusion sepsis.

PMID- 7570921
TI  - Abnormal neutrophil phenotype and neutrophil FcRIII deficiency corrected by bone
      marrow transplantation.
AB  - BACKGROUND: Neutrophils from a patient in first remission of acute myeloid
      leukemia were found to lack NA1 and NA2 alloantigens. This NA null phenotype was
      converted to the normal phenotype of NA1, NB2 by the transplantation of bone
      marrow from an HLA-identical sibling. To investigate the inherited or acquired
      nature of this rare phenotype, a combination of conventional neutrophil serology
      and recently developed restriction fragment length polymorphism (RFLP) and
      polymerase chain reaction (PCR) assays was used. STUDY DESIGN AND METHODS:
      Diagnosis, remission, and posttransplant patient peripheral blood samples were
      used for neutrophil phenotyping by granulocyte agglutination and
      immunofluorescence tests. The presence and dose of the gene for neutrophil Fc
      gamma RIIIb (Fc gamma RIIIB) were tested for with RFLP and Southern analysis and
      PCR-based RFLP tests. Plasma levels of circulating soluble Fc gamma RIII (sFc
      gamma RIII) were measured with radioimmunoassay. The sibling bone marrow donor
      and the patient's parents were also studied. RESULTS: RFLP analysis of DNA
      obtained from the patient at the time of diagnosis showed that she lacked the Fc
      gamma RIIIB gene for neutrophil Fc gamma RIII (i.e., Fc gamma RIIIb), but that,
      in DNA prepared from posttransplant samples, the Fc gamma RIIIB gene was present.
      Quantitation of plasma levels of soluble FcRIII (sFcRIII) demonstrated a complete
      absence of sFcRIII in the patient's pretransplant plasma. However, 20 units of
      sFcRIII were detected in the patient's plasma by 160 days after graft. Hair
      samples from the patient provided sufficient nonhematopoietic, genomic DNA to
      confirm that her genotype was NA0NA0. DNA prepared from lymphocytes of both
      parents and the sibling marrow donor was used to quantitate their Fc gamma RIIIB
      gene dose. The mother and brother had only one Fc gamma RIIIB gene each, while
      the father apparently had a normal complement of two Fc gamma RIIIB genes.
      CONCLUSION: In this case, an inherited absence of Fc gamma RIIIB gene in a
      patient with acute myeloid leukemia was unintentionally corrected by the
      transplantation of bone marrow from a sibling donor who himself carried only one
      Fc gamma RIIIB gene.

PMID- 7570922
TI  - Transfusion and the immune system: a paradigm shift in progress?

PMID- 7570923
TI  - A very simple method for counting white cells in platelet units collected by
      apheresis.

PMID- 7570924
TI  - An improved method for polymerase chain reaction typing of granulocyte antigens
      NA1 and NA2.

PMID- 7570925
TI  - The use of EDTA plasma obviates the need for prewarmed tests.

PMID- 7570927
TI  - American Association of Blood Banks 48th annual meeting. New Orleans, Louisiana,
      November 11-15, 1995. Abstracts.

PMID- 7570926
TI  - Risk of late human immunodeficiency virus type 1 seroconversion in United States
      soldiers whose initial screening tests were reactive.

PMID- 7570928
TI  - The safety of blood donation--is it what it should be?

PMID- 7570930
TI  - Prevention of transfusion-associated Chagas' disease: efficacy of white cell
      reduction filters in removing Trypanosoma cruzi from infected blood.
AB  - BACKGROUND: Transfusion-associated Chagas' disease (TA-CD) is a worldwide
      problem. Measures adopted to prevent TA-CD include the clinical and serologic
      screening of blood donors and/or the inactivation of Trypanosoma cruzi present in
      collected blood, using gentian violet as the trypanocidal agent. This study
      investigated the efficacy of white cell-reduction filters in removing T. cruzi
      from infected blood. STUDY DESIGN AND METHODS: Human blood was contaminated with
      2 or 150 T. cruzi parasites per mL and then left unfiltered or filtered with
      white cell-reduction filters that provided either 2, 3, or 6 log10 white cell
      removal. The efficacy of the parasite removal of these filters was evaluated by
      microscopic enumeration of active forms of T. cruzi both in vivo and in vitro.
      The in vivo experiments were done in Swiss mice that had been intraperitoneally
      inoculated with T. cruzi-infected human blood. The in vitro experiments were
      performed with fresh human blood that had been deliberately contaminated with T.
      cruzi. RESULTS: The number of parasites seen in mice inoculated with unfiltered
      blood containing 2 or 150 parasites per mL was significantly higher than the
      number of parasites seen in mice inoculated with blood from the same sample, but
      filtered with white cell-reduction filters providing 3 or 6 log10 white cell
      removal. Fifty to 70 percent of the mice given T. cruzi-infected (2 parasites/mL)
      filtered blood did not develop T. cruzi infection. In vitro, the use of white
      cell-reduction filters, providing 2, 3, or 6 log10 white cell removal,
      significantly reduced the number of parasites seen in culture. CONCLUSION: The
      present experimental data provide evidence that white cell-reduction filters are
      effective in reducing the number of parasites in T. cruzi-infected blood and that
      this efficacy depends, in part, on the concentration of parasites in the
      artificially infected blood. Properly designed clinical studies of known carriers
      of T. cruzi must be conducted to determine whether the use of white cell
      reduction filters may be an alternative method of reducing the incidence of TA
      CD.

PMID- 7570929
TI  - Cost-effectiveness of blood transfusion and white cell reduction in elective
      colorectal surgery.
AB  - BACKGROUND: The use of white cell (WBC)-reduced blood in elective colorectal
      surgery appears to reduce the frequency of postoperative infection. The question
      to be addressed is whether the cost:benefit ratio justifies the recommendation
      that WBC-reduced blood should be used for all colorectal surgery. STUDY DESIGN
      AND METHODS: Patients admitted for elective colorectal surgery (n = 197) were
      randomly assigned to receive transfusion consisting of whole blood or WBC-reduced
      whole blood. Postoperative complications, postoperative stay, and hospital
      charges were compared. RESULTS: Forty-eight patients received WBC-reduced whole
      blood, 56 received unfiltered whole blood, and 93 received no transfusion.
      Postoperative infections were significantly higher (p < 0.001) in the group that
      received unfiltered whole blood. That group also had longer hospital stays: 17
      days as compared to stays of 10 and 11 days for the group receiving no
      transfusion and the group receiving filtered whole blood transfusions,
      respectively (p < 0.01). The total hospital cost per patient receiving unfiltered
      whole blood was $12,347, as compared to $7,867 for those who received WBC-reduced
      whole blood and $7,030 for those who received no transfusion. CONCLUSION: The use
      of WBC-reduced whole blood transfusions in elective colorectal surgery
      significantly reduces the frequency of postoperative infection, the length of
      hospital stay, and the total hospital charges for patients needing blood
      transfusion.

PMID- 7570931
TI  - Prestorage white cell reduction in saline-adenine-glucose-mannitol red cells by
      use of an integral filter: evaluation of storage values and invivo recovery.
AB  - BACKGROUND: Prestorage white cell (WBC) reduction in blood components may
      decrease the incidence of adverse reactions and improve component quality. A
      bottom-and-top system with an integral third-generation WBC-reduction filter has
      been studied. STUDY DESIGN AND METHODS: Whole blood was collected from 30 healthy
      donors: from 20 by using a blood container system with an integral filter and
      from 10 controls by using a standard blood container system. Ten test units were
      buffy coat-depleted, stored for 72 hours at 4 degrees C, and then filtered, while
      an additional 10 test units were buffy coat-depleted and filtered at room
      temperature within 8 hours of collection. All units were stored at 4 degrees C
      for 42 days and sampled weekly. RESULTS: The mean WBC content of the 72-hour, 4
      degrees C units was 0.33 x 10(6), that of the room-temperature units was 2.6 x
      10(6), and that of the buffy coat-depleted controls was 460 x 10(6) (p < 0.0005).
      No significant differences were found among lactate, glucose, sodium, potassium,
      and plasma hemoglobin levels in the three groups. ATP and 2,3 DPG levels were
      significantly better preserved in control units than in 72-hour, 4 degrees C
      units (p = 0.016 and p = 0.032, respectively), but not better than in the room
      temperature units. Significant differences were observed between pH values in
      filtered units and both groups of test units (p = 0.016). In biologic terms
      however, these differences were small. Red cells from an additional eight healthy
      volunteer donors were processed by an 8-hour room-temperature method and stored
      for 35 days. Studies in vivo 24-hour recovery of autologous red cells were
      performed by transfusing a radiolabeled (51Cr plus 131I-albumin) aliquot after 35
      days' storage. Good recovery (mean > 80%) was found by both the single- and
      double-isotope-label methods. Recovery was significantly greater when calculated
      by the single-isotope method (p = 0.02). CONCLUSION: The combination of buffy
      coat removal and filtration in the blood container system with an integral filter
      achieved effective WBC reduction (> or = 3 log10 reduction from whole blood)
      without biologically significant detriment to in vitro or in vivo storage values.

PMID- 7570932
TI  - Severe outcomes of allogeneic and autologous blood donation: frequency and
      characterization.
AB  - BACKGROUND: There are few published data on severe outcomes of the donation of
      blood for allogeneic or autologous use. It would be helpful if blood collectors
      could better characterize and/or predict the likelihood of significant
      complications of blood donation. STUDY DESIGN AND METHODS: Very severe outcome
      (VSO) was defined as an event requiring hospitalization. Approximately 4.1
      million American Red Cross whole-blood donation records (July 1993-March 1994)
      were reviewed for the incidence and type of VSO. RESULTS: A total of 33 VSOs
      occurred for all donations. The incidence of VSOs for allogeneic donation was 1
      (0.0005%) in 198,119 and that for autologous donation was 1 (0.006%) in 16,783 (p
      < 0.001). First-time donors were three times as likely to have a VSO. Donors > 40
      years old had 87.9 percent of the VSOs, and donors > 60 years old had 48.5
      percent. Vasovagal (66.7%) and anginal (12.1%) episodes were the most frequent
      complications, and 66.7 percent of reactions occurred at the blood collection
      site. The mean hospital stay was 1.9 days. CONCLUSION: VSO is an infrequent
      complication of all types of blood donation, but its occurrence may be associated
      with significant morbidity and cost. VSO is nearly 12 times as likely in
      autologous blood donors.

PMID- 7570933
TI  - Platelet membrane glycoproteins and microvesicles in blood from postoperative
      salvage: a study in cardiac bypass patients.
AB  - BACKGROUND: Transfusion of blood collected by intraoperative and postoperative
      salvage systems has been linked to the development of thrombocytopenia and
      disseminated intravascular coagulation. Although functional defects have been
      reported in platelets from unwashed salvaged blood, platelet membrane
      glycoprotein (GP) composition, a potentially important determinant of function
      and survival, has not been studied. STUDY DESIGN AND METHODS: Platelets from 22
      patients whose blood was salvaged at the completion of surgery were analyzed and
      compared to platelets obtained from the venous blood from the same patient.
      Platelet membranes were stained with fluorescein isothiocyanate-conjugated CD41a
      monoclonal antibody (anti-GPIIb/IIIa) to identify platelets, a phycoerythrin
      conjugated monoclonal antibody, CD62 (anti-P-selectin) to identify activated
      platelets, and CD42b (anti-GPIb) or anti-GPIb/IX to assess GPIb. Samples were
      analyzed with a flow cytometer using software. RESULTS: Platelets obtained from
      salvaged blood demonstrated lower GPIb expression (CD42b and GPIb/IX monoclonal
      antibody binding), higher P-selectin expression, and greater numbers of platelet
      derived microvesicles. CONCLUSION: The clinical significance of transfusing blood
      containing activated platelets and microvesicles merits investigation.

PMID- 7570934
TI  - Reliability of the third-generation recombinant immunoblot assay for hepatitis C
      virus.
AB  - BACKGROUND: In a confirmatory laboratory, the second-generation recombinant
      immunoblot assay (RIBA-2) was replaced by the third-generation RIBA (RIBA-3) in
      March 1993. The aim of this validation study was to compare the sensitivity and
      specificity of RIBA-2 and RIBA-3 in a routine setting, by using a validated
      hepatitis C virus (HCV) RNA polymerase chain reaction to establish plasma
      viremia. STUDY DESIGN AND METHODS: RIBA-2 testing was performed (March 1991-March
      1993) in 593 HCV RNA-positive and 1498 HCV RNA-negative subjects. RIBA-3 testing
      was performed (March 1993-May 1994) in 220 HCV RNA-positive and 530 HCV RNA
      negative subjects. All samples reacted for anti-HCV in enzyme-linked
      immunosorbent assay. RESULTS: In HCV RNA-positive individuals, the sensitivity of
      RIBA-3 was significantly higher than that of RIBA-2 (99.5% vs. 93.3%, p =
      0.0005). This was not caused by inclusion of the NS5 antigen, but by a higher
      sensitivity of the antigens c33 and c100 (RIBA-2: 94.3% and 62.6%; RIBA-3: 99.5%
      and 88.6%). Replacement of the c22 and c100 recombinant proteins by synthetic
      peptides significantly reduced nonspecific reactivity against these antigens (p <
      0.0001). Unfortunately, increased nonspecific reactivity against the modified c33
      antigen and the new NS5 antigen canceled out this effect. Two-band reactivity
      occurred more often in nonviremic persons than in viremic persons (32.7% vs.
      8.2%, p < 0.0001). Risk factors for HCV infection were less frequently observed
      in 11 blood donors with two-band reactivity than in 6 blood donors with other
      positive RIBA-3 patterns (18% vs. 83%, p = 0.03). CONCLUSION: The higher
      sensitivity of RIBA-3 significantly reduced the number of indeterminate test
      results in HCV RNA-positive persons. Confirmatory laboratories must be aware of
      the frequent occurrence of nonspecific, isolated reactivity and even nonspecific,
      two-band reactivity in anti-HCV enzyme-linked immunosorbent assay-reactive blood
      donors.

PMID- 7570937
TI  - Red cell compatibility testing in baboon xenotransplantation.
AB  - BACKGROUND: Although baboon ABO group and human anti-baboon heteroagglutinin (HA)
      titers have been considered in the selection of baboon donors for clinical
      hepatic xenotransplantation, the biologic role of these antibodies is not yet
      known. However, because of the potential importance of ABO hemagglutinins, a
      method for baboon ABO group determination is described, as are the titers of HA
      observed in both baboons and normal human donors. STUDY DESIGN AND METHODS: The
      ABO group of 62 baboons was determined by modified reverse typing. Baboon sera
      were heated and absorbed with human group O red cells. Reverse typing was then
      performed by standard techniques. HA titers at room temperature (RT) and in the
      antiglobulin test (AGT) were assessed in 10 baboons by using human red cells and
      in 33 normal donors by using baboon red cells. RESULTS: Ten (16%) baboons were
      group A, 29 (47%) were group B, 23 (37%) were group AB, and none were group O. In
      tests using human group O red cells, HA titers in 10 baboons ranged from 1 to 32
      at RT and from negative to 64 in the AGT. All 33 normal human sera contained anti
      baboon HA. Under a hemagglutination scoring system, group A persons had the
      lowest HA scores (17 +/- 15 at RT, 31 +/- 19 in the AGT), and group B persons had
      the highest HA scores (67 +/- 4 at RT, 85 +/- 9 in the AGT). CONCLUSION: Baboon
      ABO group can be easily determined by modified reverse serum typing. Both baboons
      and humans possess HAs of variable titer. Among humans, titers appear to be
      highest in group B individuals and lowest in group A. Additional studies are
      needed to determine the clinical significance of these antibodies.

PMID- 7570936
TI  - Simulated ABO and Rh blood typing.
AB  - BACKGROUND: Blood typing historically has been used to introduce students to the
      concepts of immunohematology. Risk of disease transmission has compelled school
      districts to prohibit the use of human blood in student laboratories. A method is
      needed that will safely simulate ABO and Rh typing. STUDY DESIGN AND METHODS: A
      method that uses inorganic salt solutions to simulate ABO and Rh antigens and
      antibodies was studied. Additional salt solutions and diluents were tested to
      investigate the feasibility of simulating both ABO and Rh typing in a more
      realistic medium. RESULTS: Cobalt nitrate and sodium hydroxide were found to
      successfully simulate D and anti-D, respectively. The addition of these solutions
      did not produce cross-reactions in ABO tests. Use of simulated blood as a diluent
      improved the appearance of the samples. CONCLUSION: This method can safely and
      inexpensively simulate ABO and Rh blood typing procedures and provide students
      with hands-on blood-typing experience.

PMID- 7570935
TI  - Serum hepatitis C virus (HCV) RNA: a reliable tool for evaluating HCV-related
      liver disease in anti-HCV-positive blood donors with persistently normal alanine
      aminotransferase values.
AB  - BACKGROUND: The significance of hepatitis C virus (HCV) antibodies in blood
      donors with persistently normal alanine aminotransferase (ALT) levels requires
      evaluation. STUDY DESIGN AND METHODS: The serum and the liver were assayed for
      HCV RNA. Liver histology was analyzed in 14 HCV-positive subjects who had
      repeatedly normal ALT values over a follow-up period of at least 3 months.
      RESULTS: HCV RNA was not detected in liver and serum, and liver histology showed
      minimal changes in more than one-half of the subjects (8/14), even if third
      generation recombinant immunoblot assay was positive; this demonstrated that HCV
      can be eradicated spontaneously. Moderately histopathological liver lesions were
      usually found in HCV RNA-positive subjects (6/14), but one subject had active
      disease that required interferon therapy; this shows that chronic hepatitis may
      be present in HCV-positive individuals despite repeatedly normal transaminase
      values. HCV genotypes other than 1b (II) were usually identified, and the
      presence or absence of serum and liver HCV RNA correlated completely in all 14
      patients. CONCLUSION: Serum HCV RNA should be assayed in those HCV-positive
      donors having repeatedly normal transaminase activity; if it is positive,
      indicating an ongoing HCV infection, a liver biopsy should be performed to
      measure the degree of the liver disease and determine the appropriate antiviral
      therapy.

PMID- 7570939
TI  - Transfusion-transmitted human parvovirus B19 infection in a thalassemic patient.
AB  - BACKGROUND: Human parvovirus (HPV) B19 infection has been shown to be
      transmissible by clotting factor concentrates, most often resulting in
      asymptomatic seroconversion. So far, no case of B19 transmission due to single
      donor transfusion has been documented. CASE REPORT: A case of transfusion
      transmitted HPV B19 infection in a 22-year-old female thalassemia major patient
      is described. She presented with an aplastic crisis; this was followed 1 week
      later by transitory heart failure and acute tricuspid incompetence. The
      echocardiogram revealed a grade III tricuspid regurgitation and a floating
      vegetation on the atrial face of the tricuspid lateral leaflet. The tricuspid
      regurgitation and vegetation spontaneously disappeared within 15 days. Blood
      cultures for bacteria were repeatedly negative. IgM anti-HPV B19 seroconversion
      was documented in the acute phase. B19 DNA was detected by polymerase chain
      reaction and remained detectable up to 4 months after diagnosis. High-titer IgM
      anti-HPV and B19 DNA were also found in serum samples collected at the time of
      donation from one of the donors of the blood transfused before the onset of
      clinical symptoms. CONCLUSION: This case documents the transmission of HPV B19 by
      the transfusion of 1 red cell unit and the occurrence of possible transient
      cardiac involvement in this infectious complication.

PMID- 7570938
TI  - Perioperative blood transfusion and cancer recurrence: meta-analysis for
      explanation.
AB  - BACKGROUND: Meta-analysis was used to explain disagreements across observational
      studies in regard to the association between perioperative transfusion and cancer
      recurrence. STUDY DESIGN AND METHODS: Observational studies published in English
      from 1982 through 1994 were retrieved. Five or more articles published in
      complete form were identified for each of six cancer sites: colorectum, breast,
      head and neck, lung, prostate, and stomach. Necessary information for building a
      2 x 2 contingency table could be extracted from 60 studies. Summary relative
      risks (RR) reflecting the "average" adverse transfusion effect were computed for
      each cancer site by the random-effects method. Seven study characteristics were
      examined as potential explanations for the disagreements among the published
      studies. RESULTS: Before any adjustment for the effect of confounding, computed
      crude summary RRs suggested a significant (p < 0.05) deleterious transfusion
      effect in all cancer sites, except for breast. The RR of an adverse outcome was
      1.49 in colorectal cancer (95% CI, 1.23-1.79) and ranged from 1.06 in breast
      cancers to 3.62 in head and neck cancers. The disagreements among published
      studies were most marked in the case of colorectal and gastric cancers. These
      discrepancies could be explained, in part, by study design, because prospective
      investigations had not produced a significant unadjusted transfusion effect (RR =
      1.18; 95% CI, 0.93-1.51 in the case of colorectal cancer). CONCLUSION: A
      reduction in the size of the computed unadjusted transfusion effect (of an
      appropriate magnitude to adjust for the effect of confounding) might eliminate
      the significance of the average adverse effect in most studied cancer sites.
      Whether the entire unadjusted transfusion effect should be ascribed to the effect
      of confounding or whether a true, deleterious transfusion effect also exists can
      be resolved only by randomized controlled trials.

PMID- 7570940
TI  - A Bombay individual lacking H and Le antigens but expressing normal levels of
      alpha-2- and alpha-4-fucosyltransferases.
AB  - BACKGROUND: The rare Bombay phenotype is usually due to a primary genetic defect
      in an alpha-2- or alpha-4-fucosyltransferase. The present study was done to
      investigate a patient with normal transferases, who exhibits the Bombay
      phenotype. CASE REPORT: Red cells of the patient, his parents, and siblings were
      phenotyped for A, B, and H antigens. The presence of B, H, and Le transferases in
      serum and saliva was measured. RESULTS: The parents and siblings were all group
      B, Le(a-b-). The propositus was typed as Oh, Le(a-b-). His serum contained anti
      A, anti-B, and anti-H. Normal levels of B, H, and Le transferases were found in
      all family members including the patient. CONCLUSION: In an unusual case, a
      person has the Bombay phenotype, but normal levels of transferases in serum and
      saliva. A general defect in fucose metabolism seems to be the primary abnormality
      in this case.

PMID- 7570941
TI  - Posttransfusion purpura-like syndrome associated with CD36 (Naka)
      isoimmunization.
AB  - BACKGROUND: CD36 deficiency, which could lead to CD36 isoimmunization, has been
      reported in the Japanese population. CD36 isoantibody has been involved in
      platelet transfusion refractoriness. CASE REPORT: A 50-year-old woman originally
      from Corsica developed severe acute thrombocytopenia after massive transfusion.
      She was found to be CD36 deficient, and platelet immunoassays revealed a CD36
      (Naka) platelet isoantibody. Although the involvement of another mechanism could
      not be entirely ruled out, the thrombocytopenia was attributed to posttransfusion
      purpura-like syndrome. The antibody was also involved in platelet transfusion
      refractoriness. CD36 deficiency was present in two members of the patient's
      family as well. Flow cytometry studies demonstrated the absence of CD36
      expression on the surface of blood monocytes and cultured erythroblasts and
      megakaryocytes from one of the two CD36-deficient family members studied, but, in
      the absence of previous immunization, these CD36-deficient patients were not
      isoimmunized. In contrast, CD36 deficiency was not found in a population of 808
      healthy blood donors in the Paris, France, area. CONCLUSION: CD36 isoantibody
      might be involved in some cases of posttransfusion purpura and platelet
      transfusion refractoriness. These findings also confirm the extremely low
      frequency of CD36 deficiency among whites.

PMID- 7570942
TI  - Fibrin sealant: summary of a conference on characteristics and clinical uses.
AB  - The 2-day conference clearly outlined the formulations of products that are being
      developed or are commercially available in Europe. The major difference between
      products in the United States and those in Europe is that US manufacturers are
      preparing fibrin sealant that does not contain aprotinin, epsilon amino caproic
      acid, or any other type of antifibrinolytic agent, whereas antifibrinolytic
      agents are included in all such preparations used in Europe. The conference
      provided no clear consensus that such agents are essential to the efficacy of the
      product. Although many investigators believe in the clinical benefit of fibrin
      sealant, most of the studies to demonstrate efficacy have not been performed in a
      well-controlled fashion. However, fibrin sealant, if found in a controlled trial
      to have clinical efficacy, could be approved by the FDA for a narrow indication.
      Opportunities remain for greater exploration of different forms of the product,
      not only as a hemostatic agent, but as an adjunct to wound healing and as a
      matrix for delivery of drugs and proteins with other biologic activities.

PMID- 7570943
TI  - Brachial artery pseudoaneurysm following blood donation.

PMID- 7570944
TI  - Delayed reaction following ABO-incompatible transfusion.

PMID- 7570945
TI  - Mixed allogeneic chimerism achieved by lethal and nonlethal conditioning
      approaches induces donor-specific tolerance to simultaneous islet allografts.
AB  - We previously reported that donor-specific, but not third party, skin allografts
      were permanently accepted if mixed allogeneic (B10+BR-->B10) reconstitution and
      skin graft placement were performed sequentially or simultaneously in lethally
      conditioned (950 cGy) recipients. The purpose of the present study was to examine
      whether a similar outcome would occur if islets were placed coincident with the
      time of bone marrow infusion and to establish the minimum dose of cytoreduction
      sufficient to achieve chimerism and tolerance for simultaneous islet allografts.
      B10 (H-2b) mice were rendered diabetic using streptozotocin. After sustained
      hyperglycemia (> 300 mg/dl), diabetic B10 mice were irradiated (950 cGy) and
      reconstituted with 5 x 10(6) T cell-depleted (TCD) B10 + 15 x 10(6) TCD B10.BR
      bone marrow cells. Islet allografts genetically matched or disparate to the bone
      marrow donor were placed under the renal capsule within 24 hr following infusion
      of bone marrow cells. All donor-specific B10.BR mouse (H-2k) islet allografts
      were permanently accepted (n = 8; MST > or = 173 days), while 7 of 9 MHC
      disparate third-party BALB/c mouse (H-2d) islet grafts were rejected. The other 2
      allografts remained functional over 200 days posttransplantation. We recently
      established a nonlethal conditioning strategy to achieve multilineage mixed
      chimerism. We applied this model to examine whether simultaneous islet grafts
      matched to the donor would be permanently accepted if the donor was incompletely
      myeloablated. Diabetes was induced in B10 mouse recipients. Animals with
      hyperglycemia were conditioned with 500 cGy of TBI followed by an infusion of 15
      x 10(6) untreated B10.BR bone marrow cells. A simultaneous islet allograft
      matched or MHC-disparate to the bone marrow donor was performed the same day. Two
      days following bone marrow transplantation, a single dose of cyclophosphamide
      (200 mg/kg) was injected via the intraperitoneal route. Islet allografts matched
      to the bone marrow donor were significantly prolonged (n = 9; MST > or 226 days)
      and showed no evidence for chronic rejection, while MHC-disparate grafts were
      rejected (n = 5; MST = 34 days). Animals that received islet grafts but no bone
      marrow also rejected their grafts with a similar time course. These data suggest
      that permanent donor-specific tolerance to islet allografts placed coincident
      with bone marrow transplantation can be achieved after lethal as well as
      incompletely myeloablative conditioning.

PMID- 7570946
TI  - Simultaneous evaluation of nitric oxide synthesis and tissue oxygenation in rat
      liver allograft rejection using near-infrared spectroscopy.
AB  - Near-infrared (NIR) spectroscopy was applied to rat liver allografts for
      assessing nitric oxide (NO) synthesis and tissue oxygenation as a means of
      monitoring the rejection response following liver transplantation. Orthotopic
      liver transplantation was performed in rats, which were assigned to three groups
      as follows: group 1, a syngeneic combination (lewis to Lewis); group 2, an
      allogeneic combination (ACI to Lewis); and group 3, an allogeneic combination
      treated with 15-deoxyspergualin. NIR spectroscopy was performed on the grafts in
      recipients, and the relative changes in nitrosyl-Hb (NO bound to erythrocyte
      hemoglobin), oxy-Hb, and oxidized cytochrome oxidase (Cyt.aa3) were obtained. The
      level of nitrosyl-Hb was significantly elevated from postoperative day (POD) 3 in
      group 2 compared with that in group 1, which remained constant (P < 0.05). In
      group 3, the elevation was significantly suppressed. These data indicate that the
      alloimmune response is associated with a dramatic change in NO synthesis in
      grafted livers. In a separate experiment, NO synthesis was also increased after
      long cold preservation (24 hr) in syngeneic liver transplants. However, the
      increase was transient and subsided on POD 3. Levels of oxy-Hb and oxidized
      Cyt.aa3 in group 2 were significantly decreased when parenchymal disorder was
      confirmed histologically (POD 6 and 8), compared with those in group 1, which
      remained constant (P < 0.05). In group 3, both of these levels showed
      improvement. Thus, our NIR spectroscopy technique was shown to be capable of
      assessing simultaneously both the immune response and the degree of immune
      induced destruction of allograft tissue following liver transplantation through
      monitoring of NO synthesis and tissue oxygenation.

PMID- 7570948
TI  - Cystoscopic biopsies in pancreaticoduodenal transplantation. Are duodenal
      biopsies indicative of pancreas dysfunction?
AB  - Tissue diagnosis of pancreas graft dysfunction is desirable. Bladder-drained
      pancreaticoduodenal transplants allow tissue diagnosis by cytoscopic biopsy
      procedures of the pancreas and duodenum. To assess the diagnostic utility of
      duodenal biopsies, we reviewed all cystoscopically obtained pancreas and duodenal
      biopsy tissues at our institution (July 1, 1989 through September 30, 1993).
      Adequate tissue for histologic examination was obtained from 75 biopsies in 58
      recipients. Indications for cytoscopic biopsies were relative hypoamylasuria in
      85%, hematuria in 6%, hyperamylasemia in 3%, and other causes in 6%. Duodenal
      specimens were available from 52 biopsies (25 with, and 27 without, concurrent
      pancreas biopsies). Of the 27 duodenal biopsies alone, 3 were diagnostic of
      rejection, 15 had features consistent with rejection, 6 were normal, 1 showed
      fibrosis, 1 showed necrosis, and 1 was ulcerated. Thus, two-thirds of the
      duodenal biopsies alone yielded clinically relevant information resulting in
      antirejection treatment. In 25 of the duodenal biopsies, pancreas tissue was also
      available (11 simultaneous pancreas-kidney, 9 pancreas transplant alone, and 5
      pancreas after kidney recipients). Findings in both organs completely agreed in 9
      (36%) of the biopsies. In 7 (28%), rejection was suggested or diagnosed in both
      organs, although the organs were discrepant with regard to the presence of
      vascular rejection (6 pancreas, 1 duodenum). In 2 (11%), minor nonrejection
      discrepant findings were present. Therefore, in 18 of 25 (72%) pancreas-duodenal
      biopsies, treatment would not have been different if only one graft had been
      biopsied. But in the other 7 (28%), treatment would have been different if only
      the organ with negative findings had been biopsied. In 6 cases (4 duodenal, 2
      pancreas), rejection was seen in one organ but not the other. In 1 case,
      cytomegalovirus (CMV) inclusions were present in the duodenum, but the pancreas
      was normal. We conclude that (1) the duodenum and pancreas can reject
      independently of each other, and a negative biopsy does not preclude rejection of
      the other organ; (2) duodenal biopsies determined therapeutic decisions one-fifth
      of the time when both tissues were available for examination, and two-thirds of
      the time when only duodenal tissue was available; and (3) since cystoscopy allows
      easy access to the duodenum, both the pancreas and duodenum should be biopsied
      whenever possible; tissue samples of one organ alone are sufficient only with
      positive findings.

PMID- 7570947
TI  - Surfactant dysfunction in lung preservation.
AB  - We studied the effect of lung preservation on the surfactant system in rats. Lung
      surfactant is necessary to maintain normal lung mechanics, and hence normal lung
      function. We evaluated lung mechanics with pressure-volume (P-V) curves, and
      analyzed biochemical changes of surfactant in bronchoalveolar lavage (BAL) fluid.
      Additionally, we determined wet to dry weight ratios (W/D). We defined five study
      groups. In group I (controls) we harvested lungs without pulmonary artery
      flushing, then evaluated them immediately. In group II we flushed lungs through
      the pulmonary artery (PA) with hypothermic modified Euro-Collins solution (mECS),
      then removed and studied them immediately to determine the consequences of PA
      flushing alone. In groups III, IV, and V we flushed lungs with mECS, then stored
      them in normal saline (NS) for 6 hr (group III); in NS for 12 hr (group IV); or
      in mECS for 12 hr (group V). In groups III, IV, and V we evaluated lungs after
      storage. All four experimental groups showed significant changes in lung
      mechanics and surfactant biochemistry, compared with controls. Lungs in groups
      III, IV, and V showed additional changes in lung mechanics and surfactant
      biochemistry compared with group II. The W/D in stored lungs (groups III, IV, and
      V) was significantly higher than in controls and group II. We conclude that lung
      preservation induces deleterious changes in the surfactant system. Surfactant
      alterations are evident immediately after pulmonary artery flushing, and increase
      in severity with storage.

PMID- 7570949
TI  - Epstein-Barr virus DNA in peripheral blood leukocytes of patients with
      posttransplant lymphoproliferative disease.
AB  - We tested the hypotheses that Epstein-Barr virus (EBV) DNA levels in peripheral
      blood leukocytes (PBL) of transplant recipients with posttransplant
      lymphoproliferative disease (PTLD) (1) exceed those of patients without PTLD, (2)
      rise with or before clinical detection of the disease, and (3) fall with
      effective therapy. Using the polymerase chain reaction (PCR) and an endpoint
      dilution technique, we compared EBV DNA levels in sequential specimens from 5
      patients with PTLD, 16 solid organ transplant recipients without PTLD, and 5
      young adults with primary infectious mononucleosis (IM), and in single specimens
      from 21 healthy seropositive subjects. EBV DNA levels in the first two groups
      rose with induction of immunosuppression despite prophylactic acyclovir. Markedly
      elevated levels of EBV DNA were seen in 4 of 5 patients with PTLD at or before
      clinical diagnosis. The peak levels in these patients exceeded those of
      transplant recipients without PTLD (P = 0.02) and healthy adults with IM (P =
      0.02). EBV DNA levels fell dramatically with effective therapy. Four of 21
      healthy seropositive subjects demonstrated low levels of EBV DNA, similar to
      levels seen late in the course of patients with IM. We conclude that a
      semiquantitative PCR assay for EBV DNA in PBL can assist in the detection of PTLD
      and in monitoring the effect of therapy.

PMID- 7570950
TI  - Lack of correlation between the magnitude of preservation injury and the
      incidence of acute rejection, need for OKT3, and conversion to FK506 in
      cyclosporine-treated primary liver allograft recipients.
AB  - In order to study further whether a relationship exists between the extent of
      ischemia-preservation-reperfusion injury (IPRI) and acute rejection (AR) events
      in liver allografts, we retrospectively reviewed 213 consecutive cyclosporine
      treated patients who received their first liver allograft between 1/1/93 and
      12/31/93. Of these, 178 fulfilled the study inclusion criteria. The extent of
      IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax)
      observed within the first 72 hr posttransplant. For the purpose of univariate
      analysis, categorical classification of recipients was done based upon ASTmax as
      follows: group 1, ASTmax < 600 IU/L (n = 43); group 2, ASTmax 600-2000 IU/L (n =
      86); and group 3, ASTmax > 2000 IU/L (n = 49). For multivariate analysis,
      stepwise Cox regression was performed with age, ASTmax, and UNOS status as
      covariates. At a median follow-up of 271 days there were no statistically
      significant differences between groups with respect to the incidence of a first
      episode of AR (47%, 55%, 51%, respectively, P = NS), the timing of AR (respective
      medians, 9, 10, and 10 days, P = NS), or the proportion of patients treated with
      OKT3 (9%, 20%, 12%, respectively, P = NS) or converted to FK506 (16%, 12%, 10%, P
      = NS). Cox regression confirmed the lack of an independent association between
      the extent of IPRI and any of these outcomes. We conclude that in UW-preserved,
      cyclosporine-treated primary liver allografts, no correlation exists between the
      extent of IPRI and the incidence, timing, severity, or refractoriness of
      clinically defined AR events.

PMID- 7570951
TI  - Circulating ICAM-1, E-selectin, IL-2 receptor, and HLA class I in human small
      bowel, liver, and small bowel-plus-liver transplant recipients.
AB  - Recently, soluble(s) circulating isoforms of intercellular adhesion molecule-1
      (sICAM-1) and sE-selectin (formerly endothelial leukocyte adhesion molecule-1)
      have been described in normal human serum. Elevated levels have been reported in
      acute and chronic inflammatory disorders, including allograft rejection. In this
      study, plasma levels of sICAM-1 and sE-selectin were determined in groups of
      tacrolimus (FK 506)-treated adult patients following either isolated small bowel
      (SB), liver, or combined SB plus liver (SB/L) transplantation. Each molecule was
      measured at 1, 2, 4, 6, 8, and 12 weeks (all patients) and at 6, 9, and 12 months
      after transplantation (SB and SB/L only) by enzyme linked immunosorbent assay.
      Levels were compared with those of soluble interleukin-2 receptor (sIL-2R; a
      marker of lymphocyte activation) and soluble HLA class I (which has been reported
      to be elevated in liver transplant-related complications). Elevations above
      normal in mean plasma levels of sICAM-1 (2.4-fold), sE-selectin (1.8-fold), sIL
      2R (10.6-fold), and sHLA class I (1.3-fold) were found in patients with stable
      isolated SB grafts during the first 12 weeks posttransplant. Except for sHLA
      class I, levels of each protein were subsequently reduced, up to 1 year
      posttransplant. However, further increases in sICAM-1 and in sIL-2R and sE
      selectin levels were observed during episodes of SB rejection compared with
      stable grafts. Mean levels of all molecules were higher in patients with isolated
      SB grafts compared with those given liver or combined (SB/L) transplants, either
      during stable SB graft function (up to 12 weeks posttransplant) or rejection. The
      data demonstrate increased adhesion molecule production/shedding following SB
      transplantation and are suggestive of a reduced overall level of immune
      activation in liver and SB/L compared with isolated SB transplantation.

PMID- 7570952
TI  - In vitro stimulation of human endothelial cells by sera from a subpopulation of
      high-percentage panel-reactive antibody patients.
AB  - We have studied a serum activity that enhances in vitro ICAM-1 expression by
      human endothelial cells (EC) and report that this activity can be found in
      approximately 8% of pretransplant serum samples from individuals with a history
      of high %PRA. Hence, most high %PRA sera lack this activity, and, furthermore,
      mixing these negative sera does not result in an active serum pool. In patients
      with active serum, the ICAM-1 enhancing activity is found only sporadically,
      despite the continuous detection of endothelial-reactive antibodies. Absorption
      of Ig from a high %PRA serum reduced ICAM-1 enhancing activity, as well as
      endothelial-reactive antibodies. However, enhancing activity can sometimes be
      observed in sera that lack detectable endothelial-reactive antibodies, and none
      of several patient sera with defined MHC class I-specific alloantibodies
      displayed ICAM-1 enhancing activity. Together, these data suggest that ICAM-1
      enhancing activity may not necessarily be mediated by anti-MHC alloantibodies. In
      addition to influencing this expression, ICAM-1 active patient sera also
      influence EC expression of VCAM-1 and MHC class I, but not MHC class II
      molecules, a pattern that is similar to that stimulated by TNF alpha. However,
      coincubation of EC with active serum plus soluble TNF receptor did not block the
      endothelial phenotypic changes, despite the ability of the soluble receptor to
      completely abrogate endothelial changes induced by TNF alpha. IFN gamma also
      increases endothelial ICAM-1 expression, but has response kinetics different from
      that of active serum. Interestingly, brief treatment of endothelial cells with
      IFN gamma greatly increased the amount of IgG bound from the active sera by EC.
      We conclude that some pretransplant patients occasionally express an activity in
      their serum that influences EC expression of several adhesion molecules,
      including ICAM-1, VCAM-1, and MHC class I. This activity may be associated with
      alloantibodies, but is independent of MHC class I-reactive antibodies,
      circulating TNF alpha, or IFN gamma. The relevance of a serum-borne component
      capable of activating EC is discussed.

PMID- 7570953
TI  - The effect of dietary polyunsaturated fatty acids (PUFA) on acute rejection and
      cardiac allograft blood flow in rats.
AB  - For six weeks, recipient (Lewis RT11) and donor rats (LBNF11/n) were fed three
      diets that varied only in their lipid content. Diet A (MO) contained 19.5%
      menhaden oil and 0.5% safflower oil and was rich in omega 3 PUFA; diet B (SO) was
      20% safflower oil rich in omega 6 PUFA; and diet C (BT) was 20% beef tallow rich
      in omega 9 monounsaturated fatty acids and saturated fat. In the first set of
      graft survival studies a group fed laboratory chow was included (CHOW).
      Heterotopic cardiac transplantation from donor to recipient animals was performed
      after the six-week feeding period. The effect of these diets on cardiac allograft
      survival, mixed lymphocyte response, and blood flow in the rejecting grafts was
      investigated. The median graft survival in days was significantly prolonged in
      the rats maintained on either MO (12 days) or SO (14.5 days) compared with the BT
      (8 days)-or lab chow (7.5 days)-fed animals (P < 0.05). Cyclosporine (CsA)
      administered at subtherapeutic levels further increased the differences between
      the PUFA-fed animals and the BT-fed group. The myocardial blood flow of the
      rejecting allografts was measured using an 85Sr-labeled microsphere technique on
      the fifth posttransplant day. Flow was greatest in the MO-fed group, and both MO
      and SO groups had significantly higher myocardial blood flow than BT-fed rats (P
      < 0.05) or those bearing isografts. The allogenic mixed lymphocyte responses of
      peripheral blood mononuclear cells (PBMC) and splenic lymphocytes were suppressed
      in MO- and SO-fed groups compared with BT-fed animals. The immunosuppressive
      effect of dietary PUFA warrants further investigation, and their use as a
      possible adjunctive treatment in organ transplantation should be considered.

PMID- 7570955
TI  - Burn injury impairs second-set rejection and CTL reactivity in mice primed by
      cultured keratinocyte allografts.
AB  - Cultured keratinocyte (CK) allografts have limited antigenicity and have been
      used as a skin replacement in patients with massive thermal injury. Recent data
      indicate that CK grafts are more immunogenic than previously believed and could
      compromise wound healing in the immunocompetent host. The purpose of this study
      was to determine if the immunosuppression of burn injury might affect the
      alloantigen response and minimize sensitization to CK allografts. CBA mice
      received a 0%, 20%, or 40% burn that was partially excised three days later and
      grafted with a full-thickness (FT) skin allograft, CK allograft, or CK autograft.
      Two weeks postburn, mice received FT tail skin allografts, which were observed
      for rejection. We observed that FT and CK allografts primed the unburned host
      with equal efficacy. However, burn injury selectively minimized priming by CK
      allografts, resulting in delayed rejection of second-set allografts. With
      evidence that burn injury inhibits host sensitization to CK allografts, we then
      examined the effect of burn size on CTL alloreactivity. Additional CBA mice
      underwent burn injury, excision, and grafting as described above. Host
      splenocytes were harvested two weeks later and tested on radiolabeled targets for
      allospecific cytotoxicity. CTLs from unburned mice primed with FT allografts
      demonstrated the greatest CTL lysis, followed next by CTLs from unburned mice
      covered with CK allografts. Burn injury inhibited CTL activity as a function of
      wound size. Activity of CTLs from burned mice primed with CK allografts improved
      after in vitro allostimulation but remained below that of CTLs from unburned,
      unprimed mice. We conclude that burn injury selectively inhibits the allospecific
      response to CK allografts. The decreased immunogenicity of CK allografts, when
      used for burn wound coverage, may improve the long-term survival of allogeneic
      keratinocytes, enhancing their potential as a biologic skin replacement.

PMID- 7570954
TI  - Patterns of inflammatory vascular endothelial changes in murine liver grafts.
AB  - We have investigated the vascular endothelial phenotypes found at various times
      posttransplant in murine B10-->C3H liver grafts. In this model, liver allografts
      are spontaneously accepted, and survive indefinitely unless the recipient is
      first allosensitized with a skin allograft, in which case the liver allografts
      are rejected within five days. In our previous studies, allograft inflammation
      was associated with the development of vascular endothelial reactivity with the
      mAbs MECA-32 and M/K-2 (anti-VCAM-1). We observed that vascular endothelia in
      both liver isografts and allografts develop reactivity with MECA-32 mAb within
      two days of transplantation, indicating endothelial activation in both
      situations. In contrast, only the endothelia in liver allografts develop VCAM-1
      expression, as detected with M/K-2 mAb. VCAM-1 was expressed in both rejecting
      and accepting liver allografts, demonstrating that endothelial VCAM-1 expression
      is indicative of ongoing graft inflammation but not necessarily graft rejection.
      Liver parenchymal cells did not appear to develop reactivity with either antibody
      under any of the conditions tested. In contrast, bile duct epithelia developed
      M/K-2 reactivity (VCAM-1 expression), but not MECA-32 reactivity in liver
      allografts, but not isografts. These data demonstrate alloantigen-dependent and
      alloantigen-independent patterns of endothelial behavior in murine liver grafts
      that are quite similar to those found in murine cardiac grafts. Further, they
      demonstrate that the expression of VCAM-1 by graft endothelia is not diagnostic
      for acute rejection of liver allografts.

PMID- 7570956
TI  - Augmentation of murine hematopoiesis by interleukin 2-activated irradiated T
      cells.
AB  - We have examined the role of T cells activated with interleukin-2 (IL-2) in vitro
      and subsequently irradiated (2500 rads), in stimulating murine hematopoiesis in a
      syngeneic system. Our data suggest that activated, irradiated T (AIT) cells
      significantly increased the progenitor cell activity of T cell-depleted bone
      marrow (BM) both in vitro and in vivo as compared with controls (P < 0.001). The
      efficacy of AIT cells was comparable to that of activated, nonirradiated T (AT)
      cells (P > 0.05). Optimal stimulation of BM progenitor cell activity was seen
      when T cells were activated for 4 days and used in a BM to T cell ratio of 1:2 or
      1:5. The effect of these activated cells was related to the release of factors
      with ability to enhance hematopoiesis. These observations may have implications
      in enhancing the engraftment of T cell-depleted BM in allogeneic transplantation.

PMID- 7570958
TI  - Membrane-bound or soluble truncated RT1.Aa rat class I major histocompatibility
      antigens induce specific alloimmunity.
AB  - Transfectants that express membrane-bound (MB) or secrete soluble truncated (TR)
      rat class I RT1.Aa major histocompatibility (MHC) antigens induce alloimmunity in
      vivo. The MB-RT1.Aa was produced by transfecting the full-length RT1.Aa cDNA,
      including the alpha 1, alpha 2, and alpha 3, transmembrane and intracellular
      domains. The TR-RT1.Aa cDNA insert included only the extracellular alpha 1, alpha
      2, and alpha 3 domains; a stop codon was placed in front of the transmembrane
      domain. Following full-length sequencing, MB-RT1.Aa and TR-RT1.Aa cDNAs were
      translated in vitro into glycosylated MB-RT1.Aa (45 kDa) and TR-RT1.Aa (36 kDa)
      proteins, respectively. Each cDNA construct was individually subcloned into the
      pSG5 vector before transfection into Buffalo (BUF; RT1b) hepatoma cells. FACscan
      analysis with anti-RT1.Aa-specific R2/15S monoclonal antibody (MAb) confirmed
      surface expression of RT1.Aa molecules on the MB-RT1.Aa, but not on the TR
      RT1.Aa, transfectants. In contrast, enzyme-linked immunoadsorbent assays
      documented the presence of soluble RT1.Aa molecules in supernates from cells
      transfected with the TR-RT1.Aa, but not from cells transfected with the MB
      RT1.Aa, cDNA. Subcutaneous injection of MB-RT1.Aa or TR-RT1.Aa transfectants to
      BUF or Wistar Furth (WF; RT1u) rats induced accelerated rejection of ACI (RT1a)
      but not third-party Brown Norway (RT1n) heart allografts. Furthermore, supernates
      of TR-RT1.Aa, but not of MB-RT1.Aa, transfectants immunized WF hosts toward ACI
      hearts. Thus, both intact MB-RT1.Aa and soluble TR-RT1.Aa class I alloantigens
      induce potent sensitization against alloantigens.

PMID- 7570957
TI  - The main infiltrating cell in xenograft rejection is a CD4+ macrophage and not a
      T lymphocyte.
AB  - Porcine fetal islet-like cell clusters (ICC) or isolated rat islets were
      implanted under the kidney capsule of normoglycemic rats. The animals were
      sacrificed 1, 3, 6, 12, or 24 days after transplantation, and a detailed
      morphological and phenotypic characterization of the different cellular subtypes
      infiltrating the xenograft was performed and compared with the rejection of
      allogeneic islets. In xenograft rejection a progressive infiltration of large,
      polygonal, macrophage-like cells, which with time became the dominating cellular
      subtype, occurred. These cells expressed the CD4 antigen and the macrophage
      specific ED1 antigen. From day 6 and onward, a majority of the macrophage-like
      cells also expressed the CD8 antigen and the macrophage-specific differentiation
      antigen ED2. T lymphocytes, defined by their TCR alpha/beta or CD2 expression,
      were found in low numbers and mainly in the periphery of the graft. At the later
      stages of xenorejection a substantial number of eosinophilic granulocytes were
      also found. The allograft rejection, on the contrary, was characterized by a
      progressive infiltration of T lymphocytes, which with time became the dominating
      cellular subtype. No clear immunoglobulin or complement deposition was seen in
      the transplants before day 12, when IgG deposition was found in central necrotic
      areas of the xenograft. Previous experiments in rodents have underlined the
      crucial importance of CD4 positive cells in the xenograft rejection process.
      However, in none of these studies it was conclusively demonstrated that the CD4
      expressing cells were T lymphocytes. The presence of CD4-expressing macrophages
      heavily infiltrating the porcine xenograft seen in our study may thus be in
      agreement with previous studies in which the anti-CD4 reactive cells were
      erroneously designated T lymphocytes. Interestingly, the findings in xenograft
      rejection in the present study have striking similarities with the defense
      mechanisms active against infections by large parasites such as helminths.

PMID- 7570959
TI  - Tissue hydration in UW-preserved pancreas allografts. Evaluation with magnetic
      resonance relaxometry.

PMID- 7570961
TI  - Backtable resection of a giant cavernous hemangioma in a donor liver.

PMID- 7570960
TI  - Renal allograft thrombosis associated with the antiphospholipid antibody
      syndrome.

PMID- 7570962
TI  - Intestinal microsporidiosis occurring in a liver transplant recipient.

PMID- 7570964
TI  - Liver transplantation in a patient with high cold agglutinin titers.

PMID- 7570963
TI  - Varicella-zoster virus hepatitis and a suggested management plan for prevention
      of VZV infection in adult liver transplant recipients.

PMID- 7570966
TI  - Relationship between early liver graft viability and enzyme activities in
      effluent preservation solution.
AB  - Determination of cellular enzyme activities in washout preservation solution used
      in hypothermic liver graft storage may allow development of an index that could
      be clinically valuable in prediction of early post-transplant graft function. In
      the present study, we collected washed out preservation fluid at the time of
      graft rinsing from 53 liver recipients. Aspartate aminotransferase and, to a
      lesser extent, lactate dehydrogenase levels correlated with early postoperative
      graft viability as assessed by 1-month graft survival and standard biochemical
      indices of liver function. Those patients with the highest aspartate
      aminotransferase activity in the washout preservation solution experienced the
      highest levels of this enzyme postoperatively (area-under-the-curve day 1-3; 1340
      vs. 788 IU/L), total bilirubin (area-under-the-curve day 1-5; 901 vs. 538
      mumol/L), and rejection frequency (67% vs. 31%) (all P < 0.05), with a
      significantly lower 1-month graft survival rate compared with patients with low
      effluent levels (62% vs. 92%, P < 0.05). Two markers of endothelial cell damage,
      purine nucleoside phosphorylase and a creatine kinase isoenzyme, measured in the
      fluid did not correlate with early graft viability. It is suggested that assay of
      aspartate aminotransferase activities in preservation fluid washout samples is a
      clinically useful indicator of graft viability.

PMID- 7570965
TI  - Delayed urinary bladder leak after combined kidney-pancreas transplantation.
      Association with penile prosthesis implantation.

PMID- 7570967
TI  - Relative importance of ischemic injury and immunological injury on the
      development of transplant arteriosclerosis in rabbit aortic allografts.
AB  - The development of transplant arteriosclerosis has emerged as a major problem to
      long-term survival after heart transplantation. The accelerated development of
      arteriosclerosis in the transplanted arteries, including the aorta, could result
      either from an ischemic injury in connection with the transplantation, or from an
      immunological reaction against the transplant, or both. We evaluated
      histologically and biochemically whether extension of the ischemic period from 1
      to 24 hr has any influence on the development of transplant arteriosclerosis, in
      aorta-allografted rabbits clamped at human levels of plasma cholesterol. One set
      of rabbits was without immunosuppressive treatment (n = 10 + 9) and another
      otherwise identical set of rabbits received cyclosporine to achieve blood
      cyclosporine levels in the human therapeutic range (n = 10 + 12). The number of T
      lymphocytes in intima suggested that, in the grafts from untreated animals, an
      immunological injury had arisen, which cyclosporine reduced. A clear trend toward
      a worsening of the transplant arteriosclerosis was demonstrated as a function of
      the severity of the ischemic injury, both with and without immunosuppressive
      treatment. However, the worsening effect of maximal ischemic injury was less than
      that due to maximal immunological injury. In grafts from cyclosporine-treated
      animals, the development of transplant arteriosclerosis was significantly less
      than in grafts from untreated animals exposed to identical periods of ischemia.
      These results suggest that compared with immunological injury, ischemic injury is
      of minor importance for the development of experimental transplant
      arteriosclerosis.

PMID- 7570968
TI  - Monitoring of azathioprine-induced immunosuppression with thiopurine
      methyltransferase activity in kidney transplant recipients.
AB  - Thiopurine methyltransferase (TPMT), one of the enzymes involved in azathioprine
      metabolism, exhibits a wide range of activity in the normal population. We
      prospectively evaluated the monitoring of erythrocyte TPMT activity (using a
      radiochemical method) in kidney transplant recipients with regard to the efficacy
      of azathioprine. Three patterns in TPMT activity variation were observed. In
      group 1 patients, TPMT activity rose as early as 8 days after transplantation and
      steadily until month 3. In group 3 patients, TPMT activity remained unchanged. In
      group 2 patients, TPMT activity rose at month 1 after transplantation.
      Interestingly, the incidence of acute rejection was significantly (P < 0.01)
      different among the 3 groups, with the lowest incidence in group 1 and the
      highest in group 3. We hypothesized that TPMT activity increase was induced by
      azathioprine in the patients with the lowest incidence of acute rejection. The
      inducibility of TPMT activity would then appear to be an interesting marker of
      azathioprine-induced immunosuppression.

PMID- 7570969
TI  - Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients
      transplanted with an HCV-infected kidney.
AB  - Hepatitis C virus (HCV) genotypes, determined by polymerase chain reaction with
      type-specific primers, were studied in 5 already HCV-infected patients receiving
      kidneys from HCV-infected cadaver donors. Three patients were investigated
      retrospectively using stored pre- and posttransplantation sera and followed 18-28
      months after transplantation. Two recipients with HCV genotype 2b infection had
      received kidneys from 1 genotype 3a-infected donor. In 1 recipient, HCV 2b was
      replaced by the donor's type; in the other recipient, a prolonged mixed infection
      of 3a and 2b occurred. Persistent alanine aminotransferase (ALT) elevation (3- to
      5-fold) appeared in both patients. The third patient, also HCV 2b infected when
      transplanted with an HCV 3a-infected kidney, remained infected with HCV 2b only.
      Two patients, one with HCV genotype 1b and the other with genotype 3a, were
      followed prospectively with frequent bleeds (initially biweekly) and genotyping
      over 14 months after they had received kidneys from 1 HCV genotype 1a-infected
      donor. The HCV 1b-infected recipient remained infected with 1b only and had
      minimal biochemical signs of liver injury. In the other recipient, mixed
      infection of 3a and 1a appeared at week 3 and persisted for several weeks, until
      only genotype 1a could be detected. This patient had elevated ALT levels before
      transplantation. After onset of mixed infection, ALT levels increased further for
      several weeks, and returned to pretransplantation levels when only HCV 1a was
      found. HCV-infected kidneys transplanted into HCV-infected recipients gave 3
      different virus patterns. Most patients benefitted in the short term, but some
      super-infected patients experienced increased liver damage.

PMID- 7570970
TI  - Consistent absorption of cyclosporine from a microemulsion formulation assessed
      in stable renal transplant recipients over a one-year study period.
AB  - To evaluate the pharmacokinetic properties of the new microemulsion formulation
      of cyclosporine (Sandimmun Neoral), a double-blind, prospective study in stable
      renal transplant recipients was performed. The patients were randomized on a 4:1
      basis either to receive Sandimmun Neoral (n = 45) or continue on regular
      Sandimmun (n = 12). Before randomization, a steady-state pharmacokinetic profile
      study was performed in all patients while they were still on regular Sandimmun.
      Pharmacokinetic assessments were then performed after 8 and 12 weeks and after 1
      year. A milligram-to-milligram dose conversion was shown to be adequate to
      maintain the patients within a predefined target therapeutic window. Changes in
      pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent
      with an increased rate and extent of cyclosporine absorption from the Neoral
      formulation. This was reflected by a shorter time to reach peak concentration and
      also by a mean increase in peak concentration by 67%, and an overall mean
      increase in drug exposure (area under the curve) by 34%. These findings were also
      confirmed 1 year after conversion. Furthermore, significantly reduced
      intraindividual variability in pharmacokinetic parameters was found, as well as
      improvements in the correlation between trough concentrations and area under the
      curve after conversion to Sandimmun Neoral. In conclusion, our results indicate
      an improved and consistent absorption of cyclosporine from the Neoral
      formulation, which should make clinical management easier and safer.

PMID- 7570971
TI  - Effect of fluvastatin on lipoprotein profiles in treating renal transplant
      recipients with dyslipoproteinemia.
AB  - A single, blinded placebo-drug trial was conducted to study the efficacy and
      safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitor, in treating dyslipoproteinemia in 16 renal transplant recipients who
      had been on an immunosuppressive regimen that included cyclosporine (CsA). They
      were studied for 32 consecutive weeks, with 4 weeks of baseline treatment, 4
      weeks of placebo, 12 weeks of treatment with fluvastatin 20 mg daily, and 12
      weeks of fluvastatin 40 mg daily. Blood samples were obtained every 4 weeks for
      measurement of the lipoprotein profiles, which included total cholesterol (TC),
      triglyceride, low density lipoprotein (LDL)-, high density lipoprotein (HDL)-,
      HDL2-, HDL3- and very low density lipoprotein-cholesterol (C), apolipoprotein
      (Apo) A-1, Apo B, and lipoprotein(a). Fifteen patients completed the trial. After
      12 weeks of treatment, fluvastatin 20 mg significantly reduced TC by 13.4% (from
      6.7 +/- 0.5 [mean +/- SEM] to 5.8 +/- 0.2 mmol/L), LDL-C by 22% (from 4.1 +/- 0.3
      to 3.2 +/- 0.2 mmol/L), and Apo B by 13.2% (from 159.6 +/- 8.8 to 138.6 +/- 9.2
      mg/dl) (P < 0.005). The subsequent 12-week treatment of fluvastatin 40 mg
      significantly reduced TC by 16.4% to 5.6 +/- 0.3 mmol/L, LDL-C by 29.3% to 2.9 +/
      0.2 mmol/L, and Apo B by 18.2% to 130.6 +/- 5.5 mg/dl (P < 0.00005). There was
      no significant change in levels of other lipoproteins, including lipoprotein (a).
      There were no significant changes in the whole blood trough CsA concentrations,
      renal and liver function tests, and serum creatine phosphokinase level during
      treatment when compared with baseline and placebo. No patient complained of
      myalgia or failed to complete the study due to side effects of the drug.
      Fluvastatin appears to be safe and effective in treating dyslipoproteinemia in
      renal transplant recipients who are maintained on CsA.

PMID- 7570972
TI  - Differences in linear growth and cortisol production between liver and renal
      transplant recipients on similar immunosuppression.
AB  - Linear growth is more often impaired after liver than after renal transplantation
      (Tx) in childhood. As similar triple immunosuppression was used in our liver and
      renal transplant recipients, we were able to compare growth and endocrine
      function between 19 prepubertal liver and 35 renal transplant recipients. There
      were no significant differences in median age, weight-for-height index, or height
      standard deviation score at Tx. Seventy-eight percent of the liver Tx patients,
      but only 7% of the renal Tx patients, were below the normal range for height 3
      years after Tx. Graft function was good in both liver and renal transplant
      recipients 3 years after Tx. There was no significant difference in growth
      hormone secretion, serum insulin-like growth factor (IGF)-I, and IGF-binding
      protein-3 levels, or in methylprednisolone and cyclosporine doses. However, the
      blood cyclosporine levels were significantly higher in the liver transplant
      recipients (P = 0.001 1 year and P = 0.005 2 years after Tx). Cortisol production
      was significantly lower in the liver transplant recipients (P = 0.002 1 year and
      P = 0.049 2 years after Tx), which suggests greater steroid-mediated suppression
      of adrenal function. Growth inhibition is more often observed in liver than in
      renal transplant recipients on similar triple immunosuppression, and may not be
      related to deficient function of the growth hormone-IGF-I axis. Similar
      cyclosporine doses result in higher plasma levels of the drug and similar
      methylprednisolone doses result in more inhibited adrenal cortisol production in
      liver transplant recipients. In children with organ transplants, cyclosporine and
      methylprednisolone should be administered on an individual basis.

PMID- 7570973
TI  - Prostacyclin, thromboxane, and oxygen free radicals and postoperative liver
      function in human liver transplantation.
AB  - The aim of this prospective study is to evaluate prostanoid (prostacyclin and
      thromboxane) and lipid peroxide levels at the portal and hepatic veins, and their
      relation to immediate postoperative liver function. Nineteen patients with liver
      cirrhosis undergoing orthotopic liver transplantation were prospectively studied.
      Blood samples were obtained within 5 min and 1 and 2 hr after reperfusion of the
      new liver, through a catheter placed at the portal vein in the recipient and
      another at the left hepatic vein in the donor liver. Plasma prostacyclin and
      thromboxane were analyzed by HPLC and RIA. The formation of lipid peroxides was
      determined and expressed in terms of thiobarbituric acid-reacting substances.
      Immediate postoperative liver function was evaluated using the transaminase
      levels within the first 48 hr and the early postoperative graft function score,
      as described previously. After reperfusion, only determinations at 5 min were
      related with liver function. Either prostacyclin (R = -0.61, P = 0.004) levels at
      the hepatic vein or prostacyclin production (subtraction between hepatic and
      portal vein levels) (R = -0.47, P = 0.04) correlated significantly with the early
      postoperative graft function score. Besides, there was a significant relationship
      between lipid peroxide production as measured by thiobarbituric acid-reacting
      substances and a worse early postoperative graft function score (R = 0.61, P =
      .005). These results suggest that prostacyclin released after liver grafting
      attenuates preservation and reperfusion damage of the liver, supporting the
      hypothesis that there is an imbalance of prostanoids within the microvasculature
      in patients with a compromised postoperative liver function. Our results agree
      with the involvement of some degree of lipid peroxidation products in the damage
      of hepatocytes during anoxia and reperfusion.

PMID- 7570975
TI  - Bacterial pneumonia in recipients of bone marrow transplantation. A five-year
      prospective study.
AB  - Bacterial pneumonia as an important complication of bone marrow transplantation
      (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five
      consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month
      to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days)
      for development of bacterial pneumonia. Etiology, place acquired, chest
      radiography, and outcome were recorded and the association between bacterial
      pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%)
      patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes
      occurred within 30 days after transplantation, 10 episodes occurred on days +31
      to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the
      terminal event or contributed to fatal outcome in 8 patients (22% of bacterial
      pneumonia cases, 3% total study population). Mortality due to hospital-acquired
      pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens
      were identified in 27 (52%) episodes. During the first 100 days after BMT,
      hospital-acquired Gram-negative bacteria predominated, caused mainly by
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and
      Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria
      predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae
      occurred periodically. Considering all episodes, significant association was
      found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and
      chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive
      episodes, the association between bacterial pneumonia and VOD was significant (P
      < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and
      GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence,
      etiology, risk factors, and outcome are important considerations in its
      prevention and treatment.

PMID- 7570976
TI  - Ex vivo purging of allogeneic marrow with L-Leucyl-L-leucine methyl ester. A
      phase I study.
AB  - L-Leucyl-L-leucine methyl ester (LLME) is a lysosomatropic compound that is
      converted by dipeptidyl peptidase I to metabolites that are membranolytic for
      cytotoxic T cells, NK cells, and LAK cells. Ex vivo treatment of murine marrow
      with LLME ameliorates acute graft-versus-host-disease (GVHD), which led to
      consideration of a clinical study. A phase I study design was initiated to
      evaluate the effects of ex vivo purging of allogeneic marrow on engraftment,
      since LLME also suppresses human progenitor cells. All patients received a
      preparative regimen of cyclophosphamide plus total body irradiation. GVHD
      prophylaxis consisted of cyclosporine +/- corticosteroids. This study included 19
      patients with high risk disease undergoing allogeneic transplantation from an HLA
      identical sibling (n = 12) or a partially HLA-matched family donor (n = 7).
      Marrow mononuclear cells were treated ex vivo in a dosage escalation study with
      LLME concentrations of 0.25 mM, 0.375 mM, and 0.5 mM. Marrow NK and LAK
      activities were essentially eliminated at concentrations > or = 0.375 mM LLME.
      CD8+ cells were also reduced. Granulocyte macrophage colony-forming unit recovery
      was 3% at 0.5 mM LLME. The median time to an absolute neutrophil count of
      500/microliters was 17 days after transplantation (95% confidence interval = 14
      18 days). One patient that received marrow treated with 0.5 mM LLME died of
      secondary graft failure. Complete donor chimerism was documented in each
      evaluable case. NK recovery was delayed at LLME concentrations > or = 0.375 mM
      LLME. Grade II/IV GVHD occurred in 4/18 evaluable patients. Ex vivo treatment of
      human marrow with LLME diminishes NK activity, LAK activity, CD8+ cells, and
      granulocyte macrophage colony-forming units, but does not totally prevent acute
      GVHD.

PMID- 7570974
TI  - Selection of the living liver donor.
AB  - Living related liver transplantation offers several advantages in comparison to
      transplantation of cadaver organs. To achieve maximal donor safety evaluation,
      selection criteria and complications of the donor operation were retrospectively
      analyzed in living donors of segmental liver transplants. Seventy-three liver
      donor candidates were evaluated between October 1991 and June 1994. The median
      age of 42 mothers and 31 fathers was 31 years (range, 19-50 years). The median
      volume of the left lateral liver lobe comprised 230 ml (100-350 ml). Twenty-four
      of 73 (33%) donor candidates were not accepted for living donation. Rejection was
      due to unsuitability of the donor's liver as a graft (n = 13) or due to an
      increased risk for living donation (n = 11). Of 35 living donations performed so
      far, one was a full left hemihepatectomy and 34 were left lateral
      segmentectomies. The length of the donor operation was, on average, 4.3 hr. No
      heterologous blood was needed. Postoperative complications included death due to
      pulmonary embolism (n = 1), seizure due to a previously undiagnosed ependymoma (n
      = 1), bile duct injury (n = 1), incisional hernia necessitating late revision (n
      = 2), and duodenal ulcer (n = 2). Long-term follow-up revealed no persistent
      complications. Using our standardized protocol, 33% of young, presumably healthy
      donor candidates were rejected for living donation.

PMID- 7570977
TI  - Antithymocyte globulin preparations after heart transplantation. Cytokine
      responses in vivo and in vitro.
AB  - It is accepted that antithymocyte globulin (ATG) preparations vary in their
      bioactivity and side effects. However, this is poorly documented in the
      literature. We compared the clinical course and cytokine response of heart
      transplant patients who had received either Merieux or Stanford ATG preparations.
      The serum cytokine response (interleukin [IL]-6, tumor necrosis factor [TNF]
      alpha, IL-4, and IL-10) of 28 consecutive heart transplant recipients was
      measured for 14 days after surgery using ELISAs. The effect of various ATG
      preparations on cytokine stimulation of whole blood in vitro was also evaluated.
      There was a much greater in vivo IL-6 and TNF-alpha response to Merieux than to
      Stanford ATG (P < 0.0005). There was little IL-4 or IL-10 response with either
      preparation. No side effects could be attributed to either treatment. No
      significant difference was seen in the frequency of rejection at 30, 90, or 365
      days. More infection episodes occurred in the group treated with Stanford ATG at
      30 days (0.5 compared with 0.2 episodes/patient; P = 0.097), 90 days (1.2
      compared with 0.5 episodes/patient; P = 0.17), and 365 days (2.8 compared with
      1.8; P = 0.59), although none of these differences were statistically
      significant. When tested in vitro for cytokine stimulation, the in vivo pattern
      was confirmed, with Merieux ATG producing greater levels of TNF-alpha and IL-6
      than Stanford ATG. The differences in cytokine stimulation may be reflected in
      different immunosuppressive activities. Further research to elucidate the
      important components of immunosuppressive activity while excluding potentially
      detrimental effects is important.

PMID- 7570979
TI  - Alloantigen priming after total lymphoid irradiation alters alloimmune cytokine
      responses.
AB  - Total lymphoid irradiation (TLI) treatment represents a model of acquired
      tolerance, as TLI-treated mice develop donor-specific tolerance when exposed to
      alloantigens shortly after completing TLI. To determine whether immunoredirection
      plays a role in immunologic tolerance in TLI, we examined whether antigen priming
      in the immediate post-TLI stage altered the cytokine profile toward Th2. Compared
      with splenocytes isolated from control primed mice, the splenocytes from TLI
      primed mice failed to proliferate to immunogen in mixed leukocyte reaction
      cultures but proliferated normally to third-party alloantigen. Whole spleen and
      purified CD4 cells isolated from TLI-primed mice produced more interleukin (IL)-4
      and less gamma-interferon (IFN-gamma) in response to immunogen-bearing stimulator
      cells than controls, resulting in higher IL-4 to IFN-gamma ratios. The CD4 subset
      from TLI-primed mice contained more IL-4-producing and fewer IFN-gamma-producing
      cells, suggesting that priming after TLI shifted CD4 maturation toward Th2 cells.
      Surprisingly, TLI-primed mice contained no immunogen-responsive, IFN-gamma
      producing CD8 cells, indicating that priming after TLI abrogated development of
      this CD8 subset. In summary, the data show that priming in the immediate post-TLI
      phase shifts the allospecific memory cytokine pattern toward Th2 cytokines by
      enhancing IL-4-producing CD4 cells and preventing maturation of IFN-gamma
      producing CD8 cells. We speculate that the cytokine milieu at the time of antigen
      priming drives differentiation of the tolerogen-specific immune response toward
      Th2 cells, because splenocytes isolated immediately after TLI produced high
      levels of IL-4 and little IL-2. The enhanced Th2 pattern that developed in the
      TLI-primed mice suggests that immunoredirection may also occur in the TLI model
      of tolerance.

PMID- 7570978
TI  - Blood cyclosporine concentrations and cytomegalovirus infection following heart
      transplantation.
AB  - We have attempted to identify major risk factors for cytomegalovirus (CMV)
      infection and disease following heart transplantation, with emphasis on the
      degree and type of immunosuppression used. One hundred and eleven consecutive
      heart transplant recipients were studied for the first 4 months. Data from the 95
      who survived at least 1 month were analyzed using multiple Cox regression. Blood
      cyclosporine concentrations (CsAbc) > 550 micrograms L-1 were associated with a
      4.4-fold increase in risk of CMV infection during the next week (95% confidence
      interval = 1.2-16.2). Other significant risk factors for CMV infection included
      antirejection treatment in the past 14 days, a drop in white blood cell count,
      receiving a CMV antibody-positive donor organ, and primary diagnosis other than
      cardiomyopathy. We found that patients experiencing a CMV infection were at 3
      times the risk of subsequently developing symptomatic CMV disease (95% confidence
      interval = 1.1-9.7). In addition, the proportion of patients developing
      symptomatic CMV disease was significantly higher amongst those with a median
      CsAbc > 550 micrograms L-1 for at least 1 week (29% vs. 10%; P = 0.02) or who had
      been treated for rejection more frequently than once every 6 weeks (31% vs. 12%;
      P = 0.04) during the first 4 months. CMV antibody-negative recipients of antibody
      positive donor organs had a higher rate of symptomatic CMV disease than did other
      serological combinations (67% vs. 10%; P = 0.0001). We conclude that the risk of
      CMV infection and symptomatic disease following heart transplantation may be
      critically influenced by early management of immunosuppression as well as by
      donor serology.

PMID- 7570980
TI  - In vitro cytokine profiles and their relevance to rejection following renal
      transplantation.
AB  - Graft rejection remains an important cause of renal allograft failure, despite
      improvements in immunosuppression and HLA typing. Although HLA matching is
      beneficial, ensuring an exact match it is often impractical. Thus, a reliable in
      vitro method for quantitating and qualitating alloreactivity is an important
      goal. In this study, we measured in vitro the cytokine secretion profiles of
      mononuclear cells from patients prior to renal transplantation by stimulating
      with anti-CD3 monoclonal antibody and suppressing with cyclosporine. Mononuclear
      cells from patients who subsequently developed acute cellular rejection secreted
      higher mean levels of interleukin (IL)-2 and gamma-interferon (IFN-gamma) than
      those from patients who had no rejection episodes. IFN-gamma secretion was
      significantly associated with rejection (P = 0.002), whereas IL-2 secretion did
      not quite reach statistical significance. There was no significant correlation
      between IL-4 levels and rejection. Although cyclosporine suppressed the secretion
      of both IL-2 and IFN-gamma, there was no difference in sensitivity to suppression
      between rejectors and nonrejectors. These results further emphasize the
      importance of the TH1 lymphocyte subset in renal allograft rejection. The IFN
      gamma secretory capacity of alloreactive T cells may influence the outcome of a
      renal allograft by (1) activating graft infiltrating macrophages and/or (2) up
      regulating HLA molecules on the graft.

PMID- 7570982
TI  - Generation of nitric oxide as a rejection marker in rat pancreas transplantation.
AB  - In clinical pancreas transplantation, no reliable marker for the early diagnosis
      of acute rejection has been reported. This is one reason why the graft survival
      rate of pancreas transplantation alone is much lower than that of other organs,
      such as hearts, livers, and kidneys. We designed an experiment to investigate
      acute rejection of pancreas allografts in hyperglycemic rats by measurement of
      blood glucose levels and nitric oxide (NO) products (nitrite plus nitrate, and
      nitrosyl hemoglobin). As recipients, Lewis rats were rendered hyperglycemic by
      intravenous injection of streptozotocin before transplantation. F344 rats were
      used as donors of pancreas allografts. Lewis rats were also used as donors of
      syngeneic pancreas grafts. After transplantation, the blood glucose level
      returned to a normal level and rejection was defined as the recurrence of
      hyperglycemia. The mean survival time of pancreas allografts was 14 +/- 0.7 days.
      The plasma level of nitrite plus nitrate in allografted rats peaked on
      postoperative day 7. Electron spin resonance spectra of NO bound to hemoglobin
      were detected in the blood from allografted rats with a peak on postoperative day
      7, whereas NO bound to hemoglobin was not detected in the blood from recipients
      of syngeneic grafts at any sampling time. The results show that NO was
      synthesized in the earlier period than the elevation of the blood glucose level
      during rejection after pancreas transplantation in rats.

PMID- 7570981
TI  - Role of reactive nitrogen intermediates in the regulation of allogeneic skin
      graft survival in mice after portal vein pretransplant transfusion.
AB  - C3H/HeJ mice received multiple minor histoincompatible skin grafts (B10.BR) after
      portal or lateral tail vein injection of irradiated B10.BR spleen cells. Some
      mice were additionally injected with a competitive inhibitor of nitric oxide
      synthesis (NG-monomethyl-L-arginine [NMMA]). Skin graft survival was extended
      following portal venous immunization, and further enhanced by NMMA. Both
      treatments produced decreased production of nitrate/nitrite in vivo, and were
      associated with enhanced expression of mRNA in vivo for type 2 cytokines
      (interleukins 4 and 10), as well as increased synthesis of the latter on
      restimulation in vitro. Inducible nitric oxide synthase gene expression was up
      regulated both in the local mucosal immune system (intraepithelial lymphocytes)
      and systemically (spleen) following antigen challenge by the portal vein or by
      gavage, with or without additional NMMA treatment. In contrast, when we studied a
      possible alternate in vivo source of nitric oxide production, we found that
      endothelial cell nitric oxide synthase expression was reproducibly up-regulated
      only in splenic tissue after combined oral (or portal) immunization and NMMA, and
      was not up-regulated in tissues local to the site of injection (intraepithelial
      lymphocytes).

PMID- 7570983
TI  - Regulation of transforming growth factor-beta 1 and its receptor by cyclosporine
      in human T lymphocytes.
AB  - Scarring, fibrosis, and immunosuppression occurs with chronic cyclosporine (CsA)
      administration. We postulated that CsA may induce transforming growth factor
      (TGF)-beta 1 secretion from human T lymphocytes, a cytokine with immunoregulatory
      effects that has been implicated in the pathogenesis of wound healing and
      scarring. TGF-beta 1 was measured in serum-free supernatants harvested from T
      lymphocytes stimulated in the presence of CsA by a specific sandwich ELISA. CsA
      (10-1000 ng/ml) enhanced TGF-beta 1 secretion by approximately 40-80% in a dose
      dependent manner. Increased TGF-beta 1 secretion in the presence of CsA was
      accompanied by a 2- to 4-fold increase in TGF-beta 1 mRNA levels due to both
      enhancement of its nuclear transcription as well as prolongation of TGF-beta 1
      mRNA half-life. To determine whether the increase in TGF-beta 1 secretion was
      also accompanied by a concomitant change in its receptor, TGF-beta 1 receptor
      expression was analyzed by cross-linking of radioiodinated TGF-beta 1.
      Unactivated T lymphocytes expressed both a 105-kDa and a 65-kDa TGF-beta
      receptor. Upon stimulation, a transient increase in receptor density was seen at
      12 hr, followed by a decline at later time points. Cells treated with CsA
      exhibited at least 2-fold higher levels of TGF-beta receptors in a dose-dependent
      manner. Thus, CsA enhances the production of TGF-beta 1 protein as well as the
      expression of its receptor in activated T lymphocytes. Enhanced TGF-beta 1
      production and binding may contribute to the immunosuppressive and fibrosis
      promoting effects of CsA therapy.

PMID- 7570984
TI  - Coronary atherosclerosis in transplanted mouse hearts. IV Effects of treatment
      with monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte
      function-associated antigen-1.
AB  - Atherosclerotic lesions in the coronary arteries of transplanted mouse hearts
      manifest high expression of ICAM-1 (CD54), especially on endothelial surfaces,
      and of LFA-1 (CD11a) on migratory mononuclear cells. The possible participation
      of cellular adhesion systems in the evolution of these complex lesions was
      suggested by the increased expression of intercellular adhesion molecule-1 (ICAM
      1) and leukocyte function-associated antigen-1 (LFA-1) and also by our previous
      studies with this experimental system. In our studies, we have found that
      administration of a monoclonal antibody (mAb) to gamma-interferon will greatly
      suppress coronary changes, and gamma-interferon is known to stimulate the
      formation of these adhesion molecules. The present experiments were to evaluate
      how administration to murine heart transplant recipients of mAbs against ICAM-1,
      LFA-1, or both affected the development of coronary atherosclerosis. It was found
      that treatment with either mAb alone did not alter the severity of coronary
      atherosclerosis, but that both mAbs given together can significantly suppress
      lesion formation at 30 days compared with controls (P < 0.044). Continuing
      treatment was even more effective when extended to 60 days (P < 0.003). The mAbs
      to ICAM-1 and LFA-1 bound their targets in vivo (primarily endothelium and
      mononuclear cells, respectively), but complete, long-term saturation of combining
      sites was not attained, even with very high doses. No appreciable reduction in
      arterial endothelial ICAM-1 expression was evident. It is concluded that the ICAM
      1/LFA-1 system is of central importance in the evolution of accelerated coronary
      atherosclerosis.

PMID- 7570985
TI  - Rapamycin inhibits transplant vasculopathy in long-surviving rat heart
      allografts.
AB  - We have examined the effects of rapamycin (RPM) on transplant vasculopathy in
      long-surviving F344 rat heart allografts transplanted heterotopically into Lewis
      recipients. RPM was administered intraperitoneally for the first 14 days in
      groups 1 and 2 (0.5 and 2 mg/kg/day), and daily throughout the follow-up period
      in groups 3 (0.5 mg/kg/day) and 4 (5 mg/kg for 14 days, followed by a maintenance
      dose of 2.5 mg/kg/day). Treatment with low dose cyclosporine (CsA; 1.5 mg/kg/day)
      in combination with RPM (0.5 mg/kg/day for 14 days) (group 5) and
      immunosuppression with CsA only (5 mg/kg for 14 days, followed by 1.5 mg/kg/day)
      (group 6) were also examined. F344 isograft recipients treated with RPM (0.5
      mg/kg/day for 14 days) (group 7), those that were untreated (group 8), and hearts
      in naive F344 animals (group 9) served as controls. Grafts of group 1 were
      removed at 50, 75, 100, 150, and 200 days and infiltrating cell populations and
      surface molecules were compared with those of the other groups at 100 days. All
      allografts in treated hosts functioned > 100 days; in contrast, grafts in
      untreated recipients were rejected acutely by 8 +/- 1 days (MST +/- SD). The
      incidence of transplant vasculopathy in group 1 increased progressively (MST +/-
      SD = 10 +/- 2%, 59 +/- 7%, 85 +/- 15%, and 80 +/- 12% at 50, 100, 150, and 200
      days, respectively), as manifested by myointimal proliferation with dense
      mononuclear infiltration (predominantly ED1+ macrophages). Numbers of MHC class
      II+ infiltrating cells were prominent, as was expression of adhesion molecules
      and cytokines. The incidence of graft disease and extent of cellular infiltration
      at 100 days was significantly lower in animals receiving increased maintenance
      doses of RPM (for groups 2, 3, and 4: 25 +/- 15%, 22 +/- 11%, and 10 +/- 3%,
      respectively; P < 0.005). CsA treatment either in combination with RPM or alone
      (groups 5 and 6) failed to improve transplant vasculopathy, but reduced
      mononuclear cell infiltration. Isografts (groups 7 and 8) and naive hearts (group
      9) developed no structural abnormalities throughout the follow-up period,
      regardless of RPM treatment. We conclude that the extent of transplant
      vasculopathy can be reduced markedly in this rat cardiac transplant model with
      maintenance RPM. Addition of CsA modifies the morphological picture but does not
      improve myointimal proliferation.

PMID- 7570986
TI  - Human vascular endothelial cells do not induce anergy in allogeneic CD4+ T cells
      unless costimulation is prevented.
AB  - Human vascular endothelial cells expressing MHC class II molecules have
      previously been shown to stimulate the proliferation of allogeneic CD4+ human T
      lymphocytes. Here we show that allogeneic CD4+ T cells from individual A (TA)
      respond to class II+ endothelial cells from individual B (EB) by inducing
      interleukin (IL)-2 mRNA, detectable by semiquantitative polymerase chain
      reaction, within 12 hr. Responding T cells (TA) that are harvested after 12 hr,
      rested for 3 days, and then re-exposed to the same class II+ EB stimulators can
      again respond by proliferation that is equivalent in degree to that observed with
      third-party class II+ endothelial cells (EC) as stimulators and a little greater
      than that observed in the primary responses. Incorporation of antibodies to LFA
      3, an endothelial costimulatory molecule for T cells, or to both IL-2 and IL-2
      receptor (R) during the first-round stimulation prevented the subsequent second
      round proliferation of TA to class II+ EB but not to class II+ EC. This
      nonresponsiveness induced by anti-LFA-3 or anti-IL-2/IL-2R could be overcome by
      the incorporation of cyclosporine during the first-round stimulation or by
      incorporation of IL-2 during the second-round stimulation. These observations
      suggest that class II+ endothelial cells within allografts will not induce anergy
      in host CD4+ T cells unless costimulation is blocked or the ability of CD4+ T
      cells to respond by proliferation is prevented; even then the response may be
      modified by prevailing cyclosporine or IL-2 levels.

PMID- 7570987
TI  - Conversion of normal rats into SCID-like animals by means of bone marrow
      transplantation from SCID donors allows engraftment of human peripheral blood
      mononuclear cells.
AB  - We have recently shown that lethally irradiated normal strains of mice,
      radioprotected with SCID bone marrow, can be engrafted with human peripheral
      blood mononuclear cells (PBMC). We now demonstrate that lethally irradiated Lewis
      rats can also be radioprotected with a transplant of SCID bone marrow cells,
      administered 1 day after total body irradiation. Split chimerism was found in
      PBMC, 30 days after transplantation, with predominance of SCID donor-type cells.
      The average percentages of CD4 and CD8 T cells, of mouse or rat origin, were <
      1%. This chimerism status could be maintained for over 3 months. When human PBMC
      (300-1000 x 10(6) cells) were transplanted intraperitoneally 1 day after the
      administration of SCID bone marrow, prompt engraftment of human CD4 and human CD8
      T cells, as well as human CD20 B cells, was found in the peritoneum and in
      internal organ (such as liver, lung, spleen, thymus, and lymph nodes). T cell
      activation was high: about 50% of the cells expressed HLA-DR and almost all
      expressed CD45RO. High titers of human Ig (> 1 mg/ml) were initially found after
      2 weeks; these levels were similar to those found in the irradiated mouse model
      and in the SCID model. Likewise, marked human anti-tetanus response,
      predominantly of the IgG type, was recorded 2 weeks after the immunization,
      reaching maximal levels at 4 weeks. The triple-chimeric SCID-like rats, which
      accept as much as 1000 x 10(6) human PBMC, can potentially be used to elicit both
      antibody responses and T cell responses against specific antigens, with the
      advantages of a larger animal.

PMID- 7570989
TI  - A reassessment of ABO incompatibility in pediatric liver transplantation.
AB  - The present study examined 144 pediatric liver transplants to determine the
      impact of ABO matching on liver allograft outcome. Pediatric transplants were
      divided into 3 groups: ABO identical (ABO-Id; n = 108), ABO-compatible
      nonidentical (ABO-Comp; n = 22), and ABO incompatible (ABO-Inc; n = 14). A higher
      proportion of United Network for Organ Sharing status 4 recipients in the ABO
      Comp group (50% vs. 22% and 36% for ABO-Id and ABO-Inc, P < 0.05) and less time
      spent on the waiting list for ABO-Inc recipients (46 +/- 12 vs. 87 +/- 11 and 61
      +/- 20 days for ABO-Id and ABO-Comp, P < 0.01) were noted. OKT3 induction therapy
      was greater in ABO-Inc grafts (57% vs. 19% and 14% for ABO-Id and ABO-Comp, P <
      0.05), as was incidence of acute cellular rejection (79% vs. 59% and 41% for ABO
      Id and ABO-Comp, P = 0.08). One- and 3-year patient survival rates were 87% and
      83% in the ABO-Id group, 95% and 88% in the ABO-Comp group, and 79% and 79% in
      the ABO-Inc group (P = NS). One- and 3-year graft survival rates were 83% and 78%
      in the ABO-Id group, 87% and 80% in the ABO-Comp group, and 71% and 71% in the
      ABO-Inc group (P = NS). ABO-Inc transplantations can be performed successfully in
      pediatric recipients and warrant a reassessment of the utilization of ABO-Inc
      livers.

PMID- 7570988
TI  - Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody
      used in cadaveric renal transplantation.
AB  - A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking interleukin-2
      binding to the interleukin-2 receptor alpha-chain was evaluated in a phase I/II
      study in human renal cadaveric transplantation. The chRFT5 was well tolerated
      with no immediate adverse effects during 6 spaced infusions (from before
      transplantation to day 24) in 24 patients escalating from 2.5- to 25-mg dosages.
      The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good
      correlation between the detection of chRFT5 in the serum by radioimmunoassay, the
      coating and suppression of CD25 on T cells, and antibody activity in patient
      serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No
      antibody response to the chRFT5 was detected in any of the patients, even though
      two patients who required treatment with antithymocyte globulin or OKT3 developed
      xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There
      was a 33% incidence of rejection and the first rejection episode always occurred
      during chRFT5 therapy. Patients who did not reject during therapy did not reject
      during the first year following transplantation. Equal numbers of patients
      received dual and triple immunosuppressive therapy together with chRFT5.
      Posttransplant lymphoproliferative disorder developed in 2 patients, both on
      triple therapy, at 9 months after transplantation. The disorder did not develop
      in any patient receiving dual therapy, and no further cases have been observed to
      a minimum of 2 years' follow-up. No other viral, fungal, or bacterial infectious
      complications were prevalent in patients treated with chRFT5.

PMID- 7570990
TI  - Reflux pancreatitis after simultaneous pancreas-kidney transplantation treated by
      alpha 1 blocker.

PMID- 7570991
TI  - Liver transplantation in a patient with sickle cell anemia.
AB  - Orthotopic liver transplantation in a patient with sickle cell disease presents
      many new challenges to the transplant team. We describe the case of a 47-year-old
      patient with sickle cell disease and hepatitis C virus-induced cirrhosis who
      required liver transplantation.

PMID- 7570992
TI  - Isolation of dendritic cells in the rat liver lymph.
AB  - Lymphadenectomy of the regional lymph nodes of the rat liver resulted in the
      direct influx of peripheral hepatic lymph into the thoracic duct after
      regeneration of lymphatic vessels. Thus, we could obtain the dendritic cells in
      the hepatic lymph by cannulating the thoracic duct. By the double immunostaining,
      dendritic cells in cytosmears could be easily determined as non-B, non-T, and MHC
      class II-positive cells. The yield of dendritic cells after enrichment by the
      metrizamide density gradient was about 5 x 10(5)/first 16 hr collection/rat, with
      viability of more than 95% and purity of more than 70%. About 80% of dendritic
      cells were positive for OX62, which recognized the rat dendritic cell
      subpopulation. They showed strong stimulating activity in the primary allogeneic
      mixed leukocyte reaction. The method presented here should be applicable to
      studies of the roles of liver dendritic cells, especially in transplantation
      immunity.

PMID- 7570993
TI  - Delayed renal allograft function. Importance of the dialysis membrane.

PMID- 7570994
TI  - Detection of donor-specific microchimerism following liver transplantation.

PMID- 7570995
TI  - Segmental hepatic graft.

PMID- 7570996
TI  - Illuminating approaches to cellular physiology.

PMID- 7570998
TI  - LTP--a structural model to explain the inconsistencies.
AB  - One of the major controversies in neuroscience concerns whether the expression of
      long-term potentiation (LTP) is a pre- or postsynaptic phenomenon, with
      apparently contradictory data being the norm. The model that is outlined in this
      article combines anatomical and electrophysiological evidence to allow apparently
      contradictory data to be compatible. Development of LTP involves both influx of
      Ca2+ through NMDA receptors, and activation of another factor, perhaps the
      metabotropic glutamate receptor. These two processes might result, respectively,
      in the insertion of activation of additional postsynaptic receptors, and the
      growth of microfilaments that could split simple synapses into perforated
      synapses, consisting of multiple active zones. Whether the latter occurred, and
      at what rate, would be likely to depend on multiple factors, such as temperature,
      the metabolic state of the cell, buffering of Ca2+, and the concentration of
      factors such as nitric oxide. These subtle experimental variables would thus
      determine whether the dominant effect observed was pre- or postsynaptic.

PMID- 7570997
TI  - The use of phage display in neurobiology.
AB  - Phage display is a new technique that is used extensively in molecular biology to
      study protein-protein interaction, receptor- and antibody-binding sites, to
      produce monoclonal antibodies against diverse antigens, some of which are too
      well conserved for the production of monoclonal antibodies by traditional means,
      and to improve or modify the affinity of proteins for their binding partners.
      This technique could have many applications in neurobiology. This review
      describes the background to the technique, and illustrates a number of possible
      uses in neurobiology, ranging from the production of antibodies to non
      immunogenic proteins and to those that are available as cloned DNA sequences
      only, to the detailed study of receptor-ligand interaction using either ligands,
      their receptors or neutralizing antibodies.

PMID- 7570999
TI  - X-linked dominant Charcot-Marie-Tooth disease and other potential gap-junction
      diseases of the nervous system.
AB  - Gap junctions play important roles in the exchange of information and metabolites
      in the nervous system. These roles are highlighted by peripheral neuropathy (X
      linked dominant Charcot-Marie-Tooth disease) that is associated with mutations in
      a gap-junction protein (connexin32), resulting in loss of function, and by
      somatic dysfunctions where changes in expression, organization or function of gap
      junctions are associated with neuronal hyper- or hypoexcitability. In this
      review, the causes and consequences of this gap-junction-related peripheral
      neuropathy and other pathological conditions of the nervous system, where
      dysfunctions of junctional communication are considered to play a casual role,
      are considered.

PMID- 7571000
TI  - GABA synapses in the brain.

PMID- 7571001
TI  - Sexual differentiation of the human hypothalamus in relation to gender and sexual
      orientation.
AB  - Recently, sex differences in the structures of the human hypothalamus and
      adjacent brain structures have been observed that seem to be related to gender,
      to gender problems such as transsexuality, and to sexual orientation, that is,
      heterosexuality and homosexuality. Although these observations have yet to be
      confirmed, and their exact functional implications are far from clear, they open
      up a whole new field of physiological structural-functional relationships in
      human brain research that has so far focused mainly on such relationships in
      pathology.

PMID- 7571002
TI  - Neural networks that co-ordinate locomotion and body orientation in lamprey.
AB  - The networks of the brainstem and spinal cord that co-ordinate locomotion and
      body orientation in lamprey are described. The cycle-to-cycle pattern generation
      of these networks is produced by interacting glutamatergic and glycinergic
      neurones, with NMDA receptor-channels playing an important role at lower rates of
      locomotion. The fine tuning of the networks produced by 5-HT, dopamine and GABA
      systems involves a modulation of Ca2+-dependent K+ channels, high- and low
      threshold voltage-activated Ca2+ channels and presynaptic inhibitory mechanisms.
      Mathematical modelling has been used to explore the capacity of these biological
      networks. The vestibular control of the body orientation during swimming is
      exerted via reticulospinal neurones located in different reticular nuclei. These
      neurones become activated maximally at different angles of tilt.

PMID- 7571004
TI  - Regeneration of oligodendrocytes and myelin.

PMID- 7571003
TI  - Ion-channel assembly.
AB  - Transmembrane ion channels regulate the movement of ions (particularly Na+, K+,
      Ca2+ and Cl-) across cellular membranes, and are critical to numerous aspects of
      neurobiology. Cells express a diverse array of ion-channel proteins that vary
      widely in their ion selectivity and in their modulation by ligands (such as
      neurotransmitters) or by membrane voltage. Most ion channels are multisubunit
      proteins and, as such, undergo an intricate series of post-translational folding,
      modification and oligomerization events to achieve their correct functional
      quaternary structure. The means by which the cell is able to accomplish this
      complex process of ion-channel assembly is a topic that is beginning to be
      addressed experimentally.

PMID- 7571005
TI  - Cerebellar long-term depression might normalize excitation of Purkinje cells: a
      hypothesis.
AB  - Long-term depression (LTD) of parallel-fibre (PF) synapses on Purkinje cells is
      usually interpreted in the context of a specific theory of motor learning by the
      cerebellum proposed by Marr, Albus and Ito. Several arguments suggest that this
      theory might be false. A new hypothesis about the role of cerebellar LTD proposes
      that, under physiological conditions, LTD is autoinduced by PF inputs. This
      proposal is based on the capacity of PF inputs to trigger influx of Ca2+ into the
      dendrite. Long-term depression and other forms of Purkinje-cell synaptic
      plasticity are part of a local negative feedback loop that prevents
      overstimulation of Purkinje cells by PF inputs. This theory explains why it is
      difficult to induce LTD when a normal level of inhibition is present, and why
      inhibitory inputs are potentiated by the same conditions that can induce LTD of
      PF synapses.

PMID- 7571006
TI  - Multiple actions of cytokines on the CNS.

PMID- 7571007
TI  - Evolution and desensitization of LGIC receptors.

PMID- 7571009
TI  - Evolution and desensitization of LGIC receptors.

PMID- 7571008
TI  - Evolution and desensitization of LGIC receptors.

PMID- 7571010
TI  - Neuronal Ca2+ stores: activation and function.
AB  - The intracellular concentration of free Ca2+ ([Ca2+]i) displays complex
      fluctuations in response to a variety of stimuli, and acts as a pluripotent
      signal for many neuronal functions. It is well established that various
      'metabotropic' neurotransmitter receptors can mediate the mobilization of Ca2+
      stores via actions of inositol-polyphosphate second messengers, and more recent
      evidence suggests that 'ionotropic' receptor-mediated Ca2+ signals in neurones
      might also involve release of Ca2+ from intracellular stores. These two
      mechanisms of release of Ca2+ enable considerable temporal and spatial complexity
      of increases in the [Ca2+]i via multiple interactions at the level of
      intracellular-receptor activation. The complexity of Ca2+ signalling that is
      elicited via these interconnecting pathways might underlie mechanisms that are
      central to information transfer and integration within neuronal compartments.

PMID- 7571011
TI  - Alternatively spliced isoforms of the NMDARI receptor subunit.
AB  - Molecularly diverse forms of the NMDA-receptor subunit NRI are formed by
      alternative RNA splicing. Differential splicing of three exons generates as many
      as eight NRI splice variants, seven of which have been identified in cDNA
      libraries. The alternatively spliced exons encode a 21 amino acid sequence in the
      N-terminus domain (termed NI), and adjacent sequences of 37 and 38 amino acids in
      the C-terminus domain (termed C1 and C2, respectively). Splicing out the exon
      segment that encodes the C2 cassette removes the first stop codon, resulting in a
      new open reading frame that encodes an unrelated sequence of 22 amino acids (C2')
      before a second stop codon is reached. Differential RNA splicing alters the
      structural, physiological and pharmacological properties of receptors that
      comprise NRI subunits. Diversity of NMDA receptors is also caused by differential
      association with members of the NR2 gene family. The finding of cell-specific
      expression and developmental regulation of NRI splice variants, and of the NR2
      subunits, provides an explanation for the diversity of properties of NMDA
      receptors in different neuronal populations.

PMID- 7571012
TI  - Grasping objects: the cortical mechanisms of visuomotor transformation.
AB  - Grasping requires coding of the object's intrinsic properties (size and shape),
      and the transformation of these properties into a pattern of distal (finger and
      wrist) movements. Computational models address this behavior through the
      interaction of perceptual and motor schemas. In monkeys, the transformation of an
      object's intrinsic properties into specific grips takes place in a circuit that
      is formed by the inferior parietal lobule and the inferior premotor area (area
      F5). Neurons in both these areas code size, shape and orientation of objects, and
      specific types of grip that are necessary to grasp them. Grasping movements are
      coded more globally in the inferior parietal lobule, whereas they are more
      segmented in area F5. In humans, neuropsychological studies of patients with
      lesions to the parietal lobule confirm that primitive shape characteristics of an
      object for grasping are analyzed in the parietal lobe, and also demonstrate that
      this 'pragmatic' analysis of objects is separated from the 'semantic' analysis
      performed in the temporal lobe.

PMID- 7571013
TI  - p75 and Trk: a two-receptor system.
AB  - The neurotrophin family of survival factors is distinguished by a unique receptor
      signaling system that is composed of two transmembrane receptor proteins. Nerve
      growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3 (NT-3) and
      NT-4/5 share similar protein structures and biological functions and interact
      with two different types of cell-surface proteins, the Trk family of receptor
      tyrosine kinases, and the p75, or low-affinity neurotrophin receptor. An
      important question is whether a dual receptor system is necessary for
      neurotrophin action. Evidence indicates that co-expression of the two genes for
      the p75 receptor and the Trk NGF receptor can potentially lead to greater
      responsiveness to NGF, and suggests additional levels of regulation for the
      family of neurotrophin factors.

PMID- 7571014
TI  - [The DNA and protein content of atrial cardiomyocytes and the size and
      ultrastructure of the cardiomyocytes in children with congenital heart defects].
AB  - Right atrium myocytes were obtained during open heart surgery from 4 patients
      with atrial septal defect, and from 1 patient with Fallot's tetrad, aged from 3.5
      to 6 years. DNA and total protein contents were measured consecutively in
      isolated cells using two-wave-length scanning cytophotometry following double
      staining after Feulgen and with naphthol yellow S. All the biopsies contained
      polyploid myocytes: the number of 4c cells varied from 18 to 41%, that of 8c
      cells from 0 to 4%. The average values of cells area and protein content for
      tetraploid cells were 1.5 times higher that for diploid ones. In all the cases
      normal and little changed myocytes were dominating (69-91%). The highest number
      of cells with moderate and severe degenerative changes was registered in the
      cases of maximum degree of cell hypertrophy and polyploidization.

PMID- 7571015
TI  - [The kinetics of rhodamine 123 efflux from cells with multiple drug resistance
      under the action of energy metabolism inhibitors].
AB  - A study was made of the effects of inhibitors of ATP synthesis on the process of
      rhodamine 123 (R-123) release from sensitive sp2/0-Ag14 cells, multidrug
      resistant mouse myeloma spEBR-5 cells and hybridoma IF7, derived from spEBR-5
      cells. It has been shown that IF7 cells are cross-resistant to ethidium bromide,
      colchicine, actinomycin D and adriamycin. However, hybridoma IF7 cells, compared
      to parental spEBR-5 cells, show a lower resistance index. When studying the
      dependence of the R-123 efflux rate on glycolysis intensity (effect of 2 mM 2
      deoxyglucose) and on the level of oxidative phosphorylation activity (effect of 2
      mM KCN and 30 microM dinitrophenol), the following distinctive properties of the
      R-123 transport system of IF7 cells (compared to spEBR-5 cells) were detected: 1)
      uptake of R-123 into IF7 cells is similar to that observed for the sensitive
      sp2/0-Ag14 cells; 2) efflux of R-123 from IF7 cells takes place more intensely;
      3) R-123 transport is dependent on the rate of glycolysis and may be inhibited by
      KCN. It is found that 2,4-dinitrophenol inhibits the R-123 efflux from all the
      cells. Verapamil reverses the multidrug resistance both in spEBR-5 and IF7 cells.
      The mechanisms of multidrug resistance of cells are discussed.

PMID- 7571016
TI  - [The behavior of nucleolar proteins under the conditions of the reversible three
      dimensional separation of the structural components of the nucleolus].
AB  - The intracellular localization of Ag-proteins and protein B23 has been studied
      under the action of a low ionic strength solution (20% Hank's solution) on living
      pig cultured kidney cells (PK). For this, Ag-staining of nucleoli and indirect
      immunofluorescence using antibodies against B23 were applied. It has been shown
      that incubation of living cells in diluted Hank's solution results in migration
      of B23 from nucleoli to the nucleoplasm. A lot of Ag-proteins also migrate into
      the nucleoplasm, while part of them remained bound with the nucleolar remnants.
      Such a relocation of B23 was found to be completely reversible, and if hypotonic
      medium was replaced by the complete one, the nucleoli were able to reappear
      again, and B23 was detected solely within them. Fusion of prenucleolar bodies
      with reconstructing nucleoli could be delayed by cell incubation with actinomycin
      D. Generally, the process of nucleolar reconstitution following their artificial
      disorganization in hypotonic medium was believed to be similar to the
      nucleologenesis observed during normal mitosis. Light hypotonic treatment of
      living cells facilitates the evaluation of the number of silver grains over
      nucleoli due to their less compact arrangement than in the control.

PMID- 7571018
TI  - [The regression time of heat-shock puffs in the polytene chromosomes of
      Drosophila melanogaster as a criterion for assessing the effect of different
      stress exposures].
AB  - The time of regression of heat shock puffs was studied in the polytene
      chromosomes of Drosophila melanogaster larvae of mutant stock (1(1)ts403,
      defective in heat shock protein (HSP) system, and of the wild type stock Canton S
      after heat shock (37 degrees C), after placing of larvae to anaerobic conditions
      (dipping into physiological solution), and after combination of these treatments.
      It is shown that the time of regression of heat shock puffs depends on the
      specificity of the treatment (heat shock or anaerobic conditions), its duration
      (13 or 30 min), or on the peculiarity of functioning of HSP system in the cells
      of different stock larvae. Our results are in accordance with the idea of the HSP
      genes expression autoregulation, and allow to use the heat shock puff regression
      time as a criterion for estimation of damaging effects of stress factors.

PMID- 7571017
TI  - [The immunolocalization of the ribosomal gene transcription initiation factor UBF
      in the interphase and mitosis].
AB  - Serum P419 from a patient with rheumatoid arthritis with a high specificity
      immunolabeling nucleoli in various mammalian cells has been identified. On the
      Western blots of total cellular proteins or proteins extracted from isolated
      nucleoli it cross-reacted with a doublet of polypeptides of 97 and 94 kDa. That
      is why this serum has been concluded to recognize UBF, or RNA polymerase I
      specific transcription initiation factor. It was shown that UBF remained bound to
      the nucleoli or nucleolus organizing regions (NORs) of mitotic chromosomes
      despite the level of rDNA transcription. Nevertheless, intranucleolar
      localization of UBF was dramatically changed after partial or complete block of
      rRNA synthesis. In pycnotic cells positive labeling was found within the whole
      nucleus and cytoplasm instead of nucleolus. In metaphase UBF molecules are
      unequally distributed between the particular NORs, whereas in anaphase they are
      uniformly allocated between the daughter cells.

PMID- 7571019
TI  - [The modulation of cellular ion channel activity by arachidonic acid, its
      metabolic products and other fatty acids].

PMID- 7571020
TI  - A multicenter study of colorectal adenomas. Rationale, objectives, methods and
      characteristics of the study cohort. The Multicentric Study of Colorectal
      Adenomas (SMAC) Workgroup.
AB  - BACKGROUND AND AIMS: The Multicenter Study of Colorectal Adenomas (SMAC) is a
      retrospective-prospective cohort study involving four Gastrointestinal Endoscopy
      Units in Italy. The main aim of the study is to evaluate the relationship between
      clinical and pathologic information at index colonoscopy and subsequent incidence
      of adenoma and colorectal carcinoma. We report the rationale, objectives and
      methods of the study, including patient characteristics at initial presentation.
      METHODS: All patients were consecutively identified from the endoscopy registries
      of the four Centres from January 1, 1985 to December 31, 1992. Inclusion criteria
      were: age 18-69 years, endoscopy performed with adequate toilette at least up to
      the rectosigmoid junction, and removal of all detectable polyps. Exclusion
      criteria were: familial adenomatous polyposis, inflammatory bowel diseases,
      adenocarcinoma in adenoma with infiltrated margins, previous invasive cancer at
      any site, colon resection and geographic inaccessibility. RESULTS: Out of 20,071
      patients who underwent endoscopy at the four Centres, 11,959 fulfilled the
      eligibility criteria (5,892 males and 6,067 females, mean age = 51.1 +/- 11.6
      years). The main reasons for exclusion were age (n = 4,020) and previous or
      present colorectal cancer (n = 2,389). Symptoms were the most common reason for
      referral (72.3%), while post-polypectomy follow-up and positive fecal occult
      blood accounted for most of the remaining cases. A pancolonoscopy was performed
      in 3,088 patients (25.8%), while a left-sided endoscopy was performed in 7,887
      (66%). A total number of 4,810 polyps were removed from 2,699 patients (2,994
      adenomas, 1,580 hyperplastic polyps and 236 polyps lost after resection). A
      significant association (p < 0.001) between age and the endoscopic findings was
      observed. The subjects without polyps (n = 9,198) had the lowest age (mean =
      49.9; 95%CL = 49.6-50.1) followed by the patients with hyperplastic polyps (n =
      661; mean age = 52.3; 95%CL = 51.5-53.1), and the patients with adenomas (n =
      1,732; mean age = 56.2; 95%CL = 55.8-56.6), and the patients with hyperplastic
      polyps and adenomas (n = 306; mean age = 57.2; 95%CL = 56.3-58.2). Polyps were
      diagnosed more frequently in males than in females (28.6% versus 17.0%; p <
      0.0001). CONCLUSION: This study provides some insights in the natural history of
      colorectal cancer and stresses the need to develop adequate strategies in the
      follow-up of subjects after either positive or negative colonoscopy.

PMID- 7571021
TI  - Time trends in survival of children with acute lymphocytic leukemia in Piedmont,
      Italy: a report from the Population-Based Cancer Registry.
AB  - AIMS AND BACKGROUND: The Childhood Cancer Registry of Piedmont (RTI) periodically
      updates the life status of each registered child. Given its size, the RTI is the
      major (albeit geographically limited) Italian source of population-based survival
      rates of cancer in children. The present report describes time trends in survival
      of children with acute lymphocytic leukemia (ALL). METHODS: During 1970-87, 429
      residents in Piedmont aged 0-14 were diagnosed as having ALL: they have been
      followed up until 1991. RESULTS: Five-year survival rates increased from 21% to
      72% for children diagnosed ALL respectively in 1970-72 and 1985-87. Major
      improvements occurred up to the mid-seventies and again between cases diagnosed
      in the early and late eighties. Improvement in survival was statistically
      significant for children belonging to classes comprised between 2 and 10 years of
      age at diagnosis. Period of diagnosis was unrelated to probability of survival
      among the 13 cases diagnosed ALL at age 0. Survival was unrelated to sex, even in
      the early seventies and even after consideration of children dying more than 5
      years after diagnosis. Between 1976-81 and 1982-87, an improvement in survival
      was found in all categories of WBC count at diagnosis: the ratio between the two
      estimates was somewhat higher for children with more than 50,000 WBC/mm3 at
      diagnosis than for other children. CONCLUSIONS: Present data are compared with
      those resulting from other population-based series: this exercise can be useful
      for an overall evaluation of delivery of cancer therapy at the population basis.

PMID- 7571022
TI  - Linkage between AIDS surveillance system and population-based cancer registry
      data in Italy: a pilot study in Florence, 1985-90.
AB  - The role of the Tuscany population-based Cancer Registry (TCR) in the assessment
      of cancer incidence in AIDS patients, and the completeness of cancer reporting to
      the Italian AIDS surveillance system (RAIDS) was evaluated through a linkage
      between the TCR and the RAIDS in the period 1985-90. In the Province of Florence,
      the incidence of Kaposi's sarcoma in AIDS cases was underestimated by 24% (95%
      CI; 9.8%-47%; 6/25 cases) by RAIDS in comparison with the TCR. Of kaposi's
      sarcomas unknown to RAIDS, 2 were incident at the time of AIDS diagnosis ("truly"
      unreported cases) and 4 were late manifestations of AIDS. Moreover, 1 non-Hodgkin
      lymphoma unknown to RAIDS and 10 other malignancies (4 lung cancers) were
      identified through the TCR. In AIDS patients, the incidence of lung cancer was 95
      fold (99% CI, 16-310) the expected one on the basis of age-sex-specific incidence
      rates in the general population of the same area. Altogether, about 25% of AIDS
      cases developed a cancer during HIV infection. In spite of the small size of the
      present study, the results confirm the role of population-based cancer registries
      in the assessment of the occurrence of malignancies in AIDS patients.

PMID- 7571024
TI  - Bone hemangioendothelioma: an immunohistochemical study related to histological
      malignancy and proliferative activity (NORs).
AB  - AIMS AND BACKGROUND: Forty-four bone hemangioendotheliomas (HEs) of different
      histological grades were studied to evaluate the expression and distribution of
      laminin, type IV collagen, cathepsin G and cathepsin D in cell differentiation
      and malignancy. RESULTS: In poorly-differentiated HEs the discontinuous
      distribution of laminin and type IV collagen around angioblastic cords, tubes and
      cavities revealed an irregular and disorganized basement membrane (BM)
      architecture corresponding to an increased cell proliferation and secretion of
      cathepsin D and cathepsin G by tumor cells. CONCLUSIONS: The mean nucleolar
      organizer region (NOR) area, as a measure of cell proliferation, was
      significantly higher in grade 4 malignancies than in lower grades, revealing
      novel prognostic parameters.

PMID- 7571023
TI  - Clinical utility of radioimmunoscintigraphy of non-Hodgkin's lymphoma with
      radiolabelled LL2 monoclonal antibody, LymphoSCAN: preliminary results.
AB  - AIMS AND BACKGROUND: Adequate clinical staging of non-Hodgkin's lymphoma patients
      is essential because only localized disease can be treated satisfactorily. Many
      imaging procedures are necessary to stage the disease accurately. The objective
      of this study was to evaluate the efficacy of an antilymphoma antibody in the
      Fab' fragment form, labelled with 99mTc, to detect malignant lesions. METHODS:
      Radioimmunodetection (RAID) with 99mTc-labelled B-cell lymphoma monoclonal
      antibody IMMU-LL2-Fab' (LymphoSCAN; Immunomedics, Morris Plain, NJ, USA) was
      investigated in 10 patients (5 females and 5 males; age range, 20-72 years) with
      histologically proved non-Hodgkin's lymphoma. Of the 10 lymphomas, 7 were
      intermediate grade and 3 were low grade. Whole body images with multiple planar
      views were obtained at 30 min, 4-6 and 24 h after i.v. injection of 1 mg LL2-Fab'
      labelled with 740-925 MBq of 99mTc. SPET of the chest or abdomen was performed in
      all patients 5-8 h after the immunoreagent injection. RESULTS: No adverse
      reactions were observed in any patient after Mab infusion, and no appreciable
      changes were seen in the blood counts, renal or liver function tests. A total of
      18 of 21 (85.7%) lymphoma lesions were detected by RAID. All the tumor
      localizations were confirmed by clinical examination and with other imaging
      techniques, such as CT scan, MRI or gallium scan. In this series of patients no
      false-positive results were noted. As regards the biodistribution of the
      immunoreagent, no appreciable bone marrow activity was seen; splenic targeting
      was demonstrated in all patients; the tumor-to-non-tumor ratios ranged from 1.2
      to 2.8 ad measured by the ROI technique; no difference in uptake was noted for
      different tumor grades. The images obtained 24 h after injection did not reveal
      new lesions, but areas of doubtful uptake were seen as positive focal areas in
      the delayed scan. CONCLUSIONS: LymphoSCAN seems to be useful for detection,
      staging and follow-up of non-Hodgkin's lymphoma patients.

PMID- 7571026
TI  - Short schedule intravesical mitomycin preceding transurethral resection for
      recurrent Ta-T1, G1-G2 bladder cancer.
AB  - AIMS AND BACKGROUND: Intravesical instillations commonly follow resection, when
      all visible lesions have been removed, making impossible any direct assessment of
      efficacy. The study was conceived to evaluate the ablative effect on the tumor
      and the efficacy in reducing the risk of recurrence of short schedule
      intravesical chemotherapy administered before endoscopic resection. STUDY DESIGN:
      Four weekly intravesical instillations of mitomycin C followed by transurethral
      resection (TUR) were administered to 31 patients with recurrent small volume
      superficial bladder cancer. RESULTS: At TUR no evidence of disease was found in
      22 patients (70.9%) and residual disease in the remaining 9 (29.1%). At a median
      follow-up of 15 months (range, 3-33) 16 of 31 patients (51.6%) had recurrence of
      disease. The treatment was well tolerated. CONCLUSIONS: Short-schedule
      intravesical chemotherapy can completely ablate small volume recurrent
      superficial bladder cancer in a relevant number of patients but is probably not
      sufficient to obtain long-term prophylaxis.

PMID- 7571025
TI  - Soluble intercellular adhesion molecule-1 and serum cytokines in melanoma
      patients treated with liposomes containing muramyl tripeptide.
AB  - AIMS AND BACKGROUND: A soluble form of intercellular adhesion molecule-1 (sICAM
      1) has been recently identified in patients with malignant melanoma. It has been
      demonstrated that inflammatory cytokines can modulate the cellular expression of
      ICAM-1 and the shedding of this molecule by cells. To our knowledge, few data
      exist on serum sICAM-1 levels in cancer patients treated with immunomodulators.
      Liposomes containing muramyl tripeptide (MLV MTP-PE) can activate monocytes from
      cancer patients in vitro and in vivo, making them cytotoxic such as tumor
      necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). The purpose of the
      present study was to evaluate the levels of sICAM-1 and their possible
      correlation with serum inflammatory cytokine levels in melanoma patients treated
      with MLV MTP-PE. METHODS: The sera from 9 patients with metastatic melanoma
      treated with MLV MTP-PE, 4 mg i.v. twice a week for 12 weeks, were tested in
      ELISA system to detect sICAM-1, TNF-alpha, IL-6, Interleukin-1 beta (IL-1 beta)
      and Interferon-gamma (IFN-gamma) before, and 2 and 24 h after the 1st, 12th and
      24th infusion of MLV MTP-PE. RESULTS: Baseline levels of sICAM-1 were elevated in
      all patients (median 540 ng/ml: range 400-1030 ng/ml). Twenty-four h after the
      1st infusion of MLV MTP-PE, we observed 6 increases in sICAM-1 levels, 1 decrease
      and 2 stable values (median 720 ng/ml: range 410-1820; P = 0.060). Twenty-four h
      after the 12th infusion, sICAM-1 increased in 3 patients and did not change in 4
      (median 790 ng/ml: range 495-1650 ng/ml; P = 0.069). At the 24th infusion, sICAM
      1 increased in 4 of 6 evaluable patients and remained stable in 2 (median 802
      ng/ml: range 510-1450 ng/ml; P = 0.045). To better analyze the variations in
      sICAM-1, the patients were arbitrarily divided into two groups according to their
      clinical behavior: 4 presented stabilization (all lesions, n = 2; some lesions, n
      = 2) (Group A); 5 presented progressive disease (Group B). In Group A, sICAM-1
      levels remained stable or showed a modest increase during treatment (except in 1
      patient, who exhibited a substantial variation after the 12th infusion). In
      contrast, in Group B very high levels of sICAM-1 were observed at the beginning
      of the study therapy in 1 patient and after the 1st infusion in 3 patients; these
      values remained high until the 24th infusion. In most of the patients, TNF-alpha
      and IL-6 increased after the 1st infusion, but not thereafter. IFN-gamma was
      never detected; IL-1 beta was detectable in a few cases, but only before the
      infusions. CONCLUSIONS: baseline levels of sICAM-1 were elevated in all patients
      and further increased during treatment only in patients with more aggressive
      disease. No correlation was found between sICAM-1 and inflammatory cytokines. It
      would therefore seem that in patients with advanced disease, higher levels and a
      progressive increase in sICAM-1 may be unfavorable prognostic factors.

PMID- 7571027
TI  - Pain at tumor site after vinorelbine injection: description of an unexpected side
      effect.
AB  - AIMS AND BACKGROUND: Vinorelbine is a new semisynthetic vinka alkaloid that has
      demonstrated good tolerability and interesting activity in a large spectrum of
      solid tumors. It was the aim of this paper to report the presence of a rarely
      documented side effect. METHODS: In our experience, 135 patients were treated
      with vinorelbine during the period 10/92 to 11/94 for a total of 1080 cycles. In
      26% of the cycles, vinorelbine was administered in monochemotherapy and in 74% in
      polychemotherapy regimens. The dose of vinorelbine, administered in a weekly
      schedule, was 25 mg/m2 in 109 patients and 30 mg/m2 in 26 patients. In general,
      no analgesic premedication was used. Sixty-five patients had lung cancer, 45 had
      breast cancer, and 25 miscellaneous cancer. Only 4 patients had a previous
      history of neurotoxicity. RESULTS: Ten patients (7%) had pain in the tumor site
      within a few minutes of the vinorelbine injection. According to WHO grade, 5
      cases had moderate and 5 severe pain. Pain was always reversible. In 5 cases
      ketorolac was administered after pain detection with resolution of the symptoms;
      in 4 cases it was necessary to deliver buprenorphine. One patient was admitted to
      the coronary unit because a myocardial infarction was suspected after
      retrosternal pain and required i.v. morphine. Seven cases refused to continue the
      treatment, and 3 cases had no further problem after ketorolac premedication.
      CONCLUSIONS: Although rare, the presence of severe pain after vinorelbine
      injection may adversely affect the treatment course. Such data are helpful in the
      recognition and management of this reversible side effect.

PMID- 7571029
TI  - Long-lasting complete remission of pulmonary metastases consequent to renal cell
      carcinoma obtained with interferon-beta therapy: review of the literature and a
      case report.
AB  - This case report describes a complete remission of pulmonary metastases,
      consequent to renal cancer, achieved with interferon-beta therapy. After
      nephrectomy (July 1990), this female patient was proposed for therapeutic
      assessment: vinblastine chemotherapy was carried out for 10 cycles, whereas
      concomitant immunotherapy of interferon-alpha was discontinued after 30 days
      owing to lack of tolerability. In replacement, interferon-beta administration
      from the 5th cycle of chemotherapy at the dose of 3 MIU 3 times a week was well
      tolerated. Interferon-beta was interrupted 27 months later, due to an increase in
      transaminase levels. Partial remission of pulmonary metastases was assessed after
      9 months of interferon-beta therapy, and a complete remission was assessed after
      1 and 2 years of therapy. In November 1994, the patient was still in good
      clinical conditions and disease-free after 37 months from the achievement of
      complete remission.

PMID- 7571028
TI  - Cardiac and pulmonary effects of alpha tumor necrosis factor administered by
      isolation perfusion.
AB  - AIMS: We studied cardiac and pulmonary function in 22 patients affected by in
      transit metastases from cutaneous melanoma and metastases from soft tissue
      sarcoma of the limbs and treated with isolation perfusion in extracorporeal
      circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild
      hyperthermia. PATIENTS AND METHODS: All patients experienced a septic-like shock
      syndrome of variable severity: this feature lasted from 24 to 72 h and was
      controlled by the infusion of dopamine. Seventeen patients suffered from
      respiratory insufficiency, which required assisted ventilation (7 cases
      mechanical ventilation for 1 day, 8 cases for 2 days, and 2 cases synchronized
      intermittent mandatory ventilation). RESULTS: Spirometric parameters recorded 7
      15 days after treatment did not change from baseline values. In contrast, lung
      transfer factor for carbon monoxide significantly declined in a dose dependent
      fashion. CONCLUSIONS: Our data confirm that rTNF alpha administered by isolation
      perfusion technique induces systemic cardiovascular and pulmonary side effects.
      Further studies are required to better define time course and reversibility of
      impaired pulmonary function.

PMID- 7571030
TI  - Radiation-induced primary brain lymphoma: a case report.
AB  - A patient who developed primary brain lymphoma 6 years following whole brain
      irradiation due to a low-grade glioma is described. The patient had no evidence
      of congenital or acquired immunodeficiency state and achieved a good and prompt
      response to aggressive chemotherapy, including high-dose methotrexate. The
      previous radiation therapy is implicated in the etiology of the lymphoma because
      of the geometric coincidence, the relatively long latency period and the
      different histology. A brief review of current literature is reported.

PMID- 7571031
TI  - Malignant melanotic schwannoma or schwannian melanoma?
AB  - A 43-year-old man underwent surgical removal of L4-L5 nerve root tumor which
      bulged to the extra and intradural spaces and extended as a dumbbell through the
      intervertebral foramen. Histological examination showed pleomorphic tumor cells
      with heavy melanin pigmentation. Most of the tumor cells were
      immunohistochemically positive for vimentin, S-100 protein and HMB-45 antigen;
      basic myelin protein was detectable in single tumor cells. Electron-microscopy
      revealed melanosomes in different stages of differentiation and some
      characteristics of Schwann cells, such as redundant basal lamina production.
      Taken together the tumor showed features of histological malignancy and
      incomplete schwannian differentiation with considerable overlap between melanoma
      and malignant melanotic schwannoma.

PMID- 7571032
TI  - Head and neck metastases of renal cancer after nephrectomy: a report of 2 cases.
AB  - Two cases of metachronous metastases of renal cell adenocarcinoma are reported.
      One case presented a solitary metastasis of the ethmoid-orbit which was resected.
      The patient has remained well for the following 12 months. The second case
      presented with a secondary to the tongue and multiple metastases elsewhere.
      Electrodissection achieved a good palliative result.

PMID- 7571033
TI  - Gonadoblastoma with coexistent features of mixed germ cell-sex cord stroma tumor:
      a case report.
AB  - Gonadoblastoma and mixed germ cell-sex cord stroma tumor have been widely
      recognized as two separate entities on the basis of both clinical and
      pathological features. The typical morphological pattern of both tumor types was
      found by us to coexist in the same gonadal tumor in a 14-year-old 46,XY
      phenotypically female subject who also had a contralateral dysgerminoma. A
      subserous implant showing the mixed germ cell-sex cord pattern of the primary
      tumor was detected in the uterine body. Following therapy the patient is alive
      and well after a 7-year follow-up. The distinction between gonadoblastoma and
      mixed germ cell-sex cord stroma tumor requires discussion.

PMID- 7571034
TI  - Post-radiation angiosarcoma of the breast: a clinical case.
AB  - After conservative treatment of breast carcinoma (quadrantectomy and axillary
      dissection, plus radiotherapy), the growth of an angiosarcoma in the irradiated
      skin is a very rare event. We report a case, developed in the breast skin 62
      months after the irradiation, and discuss the therapeutic possibilities and the
      role of follow-up in these patients.

PMID- 7571035
TI  - Massively diffuse multifocal granulocytic sarcoma in a child with acute myeloid
      leukemia.
AB  - A case of granulocytic sarcoma in an 8-year-old boy with acute myeloid leukemia
      and t (8; 21) is reported. The case is of interest due to massive extension of
      the tumor, which may raise different diagnostic difficulties with other solid
      tumors such as lymphoma, Ewing sarcoma, and soft tissue sarcoma. Furthermore, the
      tumor was localized in some sites, such as the parotid region and peripheral
      nerves, which are not usually involved in granulocytic sarcoma. The case points
      out the diagnostic difficulties with this kind of tumor and appears to contribute
      to the identification of a subgroup of acute myeloid leukemia with peculiar
      features, such as M2 morphology with Auer rods, t (8; 21), granulocytic sarcoma
      and a poor prognosis.

PMID- 7571036
TI  - Feasibility of radioimmunoguided surgery of colorectal carcinoma using indium 111
      CEA specific antibody and simulation with a phantom using 2 steps targetting with
      bispecific antibody.
AB  - The study was undertaken to define the potential use of radiolabelled (Indium 111
      or Technetium 99 m) carcinoembryonic antigen specific antibody (CEA f(ab')2) for
      the radioimmunodetection of colorectal cancer using an intraoperative hand-held
      gamma probe. A clinical study performed with ten patients showed that tumor with
      good uptake of CEA specific antibody could be detected with sufficient contrast
      only in two patients. Results of a biodistribution study performed with tumor
      fragment and normal tissue countings in a gamma counter showed high tumor uptake
      in five patients. There was no correlation between tumor uptake and the count
      rates measured intraoperatively. To increase the signal/background of the gamma
      probe, a simulation study with a peritoneal cavity phantom was performed. We
      determined the efficiency of a two steps targetting method compared to the direct
      method. We simulated different tumor sizes with plexiglas balls (0.5, 1, 2, 5 ml)
      and tested two scintillators (NaI, BgO). Experiments were performed with 111 In
      and 99 m Tc. The two steps targetting method was better than direct method. The
      results of simulation with direct method radiolabelled with 111 in confirmed our
      clinical study: no efficiency of a gamma probe for the surgeon to detect a tumor.
      However the two steps targetting method (indirect labelling method) was very
      encouraging to detect tumors (size 1 and 2 ml) and definitively convincing with
      99 m Tc.

PMID- 7571037
TI  - Peroperative radioimmunodetection, PROD, of colorectal cancer using 99m-Tc PR1A3
      monoclonal antibody.

PMID- 7571039
TI  - Prevention of radiation related complications in the treatment of rectal
      adenocarcinoma. The importance of the dose volume relationship.
AB  - AIM: To illustrate and stress the role of the dose volume relationship in the
      risk of radiation induced rectal complications. METHODS: With different
      techniques of irradiation like contact x ray therapy, Iridium implant, external
      beam irradiation, intra operative electrontherapy, it is possible to irradiate
      different volumes from few centicubes to liters. RESULTS: The data from the
      literature clearly demonstrate that high doses can be given safely in small
      volumes, but that doses of 50 Gy or more in large volumes are dangerous. The
      irradiation of the whole pelvis through two antero posterior (AP - PA) fields
      ecompassing more than 4 liters should not be recommended. Other classical risk
      factors must be taken into account when planning the treatment. Previous surgery,
      obesity, diabetus, collagen disease, combined chemotherapy, all these factors can
      lead to a modification of the irradiation technique. CONCLUSIONS: A perfect
      technique of irradiation is mandatory to achieve the best therapeutic ratio when
      treating rectal cancer. To avoid severe complications the dose must be closely
      adapted to the irradiated volume.

PMID- 7571040
TI  - Radiation enteropathy.

PMID- 7571038
TI  - Adjuvant treatment in operable stage II and III rectal cancer.
AB  - AIMS AND BACKGROUND: To date adjuvant treatments of rectal cancer generally
      include radiotherapy and more recently a combination of radiotherapy and
      chemotherapy. Trials have benn generally restricted to patients with stage II and
      III rectal cancer. The purpose of the present study is to determine the efficacy
      of a preoperative combination of radiation therapy and chemotherapy in operable
      locally advanced rectal cancer. METHODS: From March 1990 to June 1994, 58
      patients with histologically documented adenocarcinoma of the rectum entered our
      protocol. 35 neoplasms were located in the lower third of the rectum and the
      remaining 23 in the middle third. At pre-treatment clinical staging 46 tumors
      were judged as stage III and 12 as stage II. Chemotherapy and radiotherapy were
      started jointly on day one of the treatment. Mitomycin-C was given as a bolus
      intravenous at a dosage of 10 mg/m2, the first day. 5-Fluorouracil was given in a
      dosage of 1000 mg./m2/day as a continuous 24 h infusion for 4 days. Radiation
      therapy was given at a total dosage of 37.8 Gy. Surgery was generally performed
      four to five weeks following completion of the radiation therapy. RESULTS:
      Patients compliance to the treatment was 96 percent. A reduction of tumor size >
      50 percent was observed in 65 percent of patients. Tumor distance from anal canal
      increased in 75 percent of patients. Morbidity rate was 31 percent; no
      postoperative mortality was reported. Histological examination of surgical
      specimens showed that in 54 percent of patients tumor disappeared or was confined
      to the rectum; there was no evidence of tumor cells in 5 cases and stage I
      lesions were diagnosed in 19 cases (35 percent). Preliminary data on recurrences
      show a 5 percent local recurrence rate and a 7 percent distant metastases rate.
      CONCLUSIONS: It may be concluded that preoperative radiochemotherapy is generally
      well tolerated; surgery does not present additional technical difficulties; the
      effect of stage reduction has been observed in a consistent number of cases.

PMID- 7571041
TI  - DNA content and cell kinetics in colorectal carcinoma: flow cytometric analysis
      of primary tumor and liver metastases.
AB  - AIMS AND BACKGROUND: Both flow cytometric DNA ploidy and proliferative activity
      have been indicated as potential prognostic indicators in colorectal cancer. Due
      to tumor biological heterogeneity, these parameters are best assessed with
      multiple sampling. METHODS: We undertook a prospective study on 52 patients with
      Duke's D colorectal tumors looking at multiple samples of the primary tumors and
      liver metastases. DNA ploidy and tumor proliferative activity (derived from
      proliferating cell nuclear antigen, PCNA FCM expression) were evaluated. RESULTS:
      Of primary tumors, 36/52 (69.2%) were aneuploid in at least 1 sample, with a
      median value of the DNA index of the aneuploid peak of 1.58. On liver metastases,
      42/52 (80.7%) patients were aneuploid in at least 1 sample with a median DNA
      index of the aneuploid peak of 1.64. Identical or nearly identical histograms
      from different tumor samples were observed in only 18/52 (34.6%) of the primary
      tumors and in 15/52 (28.8%) of the liver metastases. The PCNA values for primary
      tumors ranged from 5 to 28% (median value = 16.5%). In the liver metastases, PCNA
      values ranged from 12 to 38% (median value = 19.8%). Proliferative activity was
      lower for diploid than for aneuploid tumors. DNA ploidy and PCNA expression of
      the deep specimen of primary tumors were similar to those of the liver metastasis
      of the same patient while this concordance was not complete in the case of
      superficial biopsy specimens. CONCLUSIONS: If correctly performed, FCM techniques
      allow an accurate analysis of DNA ploidy and proliferative activity and both
      these measurements can offer considerable potential for a more comprehensive
      approach to colorectal cancer.

PMID- 7571042
TI  - Radiation enteropathy--incidence, aetiology, risk factors, pathology and
      symptoms.
AB  - The small bowel represents a dose limiting structure for the administration of
      tumoricidal abdominal and pelvic doses exceeding 4,500 cGy. If its real incidence
      remains controversial, predisposing factors and histopathologic features are
      currently well established. Contrary to the transient and self-limiting symptoms
      of acute radiation enteritis, chronic radiation enteropathy is a rare but severe
      sequelae indicing high morbidity and mortality rates. Its prevention constitutes,
      in multidisciplinary institutions, a permanent challenge both for the
      radiotherapist and the pelvic surgeon.

PMID- 7571043
TI  - Follow-up of colorectal cancer.
AB  - Surveillance for a second primary colon or rectal cancer, detection and treatment
      of recurrent disease, and health maintenance are the essential components of
      follow-up of a patient population with potentially curative resection of a
      primary large bowel cancer. The value of follow-up programs have been extensively
      studied with colorectal cancer. Of 100 colorectal cancer patients in a follow-up
      program, approximately 20 patients should have prolongation of life as a result
      of surveillance, detection and treatment, and health maintenance. Detection of
      recurrent cancer and its treatment may be the most expensive and least effective
      part of the follow-up program. Lead time is minimal with intensive follow-up
      (including serial CEA blood tests) when compared to the time of diagnosis derived
      from symptoms of recurrent malignancy in an informed patient. Aggressive
      reoperative surgery in selected patients with recurrent disease with use of
      adjunctive radiation therapy and chemotherapy when appropriate, will salvage long
      term the greatest number of people and yield some palliative benefits. It is
      crucial that reoperative surgery be pursued by an experienced team familiar with
      this type of intervention. Comprehensive follow-up of colorectal cancer patients
      has a high value in its medical economic cost and should continue to be pursued,
      studied, to become more cost effective, and integrated into a complete management
      plan.

PMID- 7571044
TI  - Local recurrences from rectal cancer: impact of previous surgery.

PMID- 7571045
TI  - Surgical management of pelvic recurrence from resected rectal cancer: technical
      aspects.
AB  - Management of local-regional recurrences of primary rectal cancer (LRR) by a
      multi-disciplinary surgical team (GI, urological and plastic surgeons) is
      presented. Aggressive treatment involving surgical debulking and intra operative
      radiation can result in local control and long term survival in 10 to 20% of the
      patients with a low mortality and morbidity. Sequelae caused by the extended
      surgical resection are limited thanks to the fast healing following omentoplasty
      associated with musculo cutaneous flaps and to the fashioning of a continent
      stoma.

PMID- 7571046
TI  - Prognostic factors for survival and disease-free survival in hepatic metastases
      from colorectal cancer treated by resection.
AB  - The prognostic factors of 219 patients submitted to Ro hepatic resection for
      colorectal metastases have been statistically analyzed. The overall 5-year
      actuarial survival rate was 24% and the 5-year disease-free survival rate was
      18%. At univariate analysis four variables resulted significant: 1) The stage of
      primary colorectal cancer: if the meserentic lymph nodes were metastatic (Dukes
      C) or uninvolved (Dukes B) 5-year survival was respectively 16 and 38% (p <
      0.001). 2) The percentage of hepatic replacement: the 5-year survival rate of
      patients with H1 (< 25%), H2 (25-50%) and H3 (> 50%) was 27, 16 and 8%
      respectively (p < 0.001). 3) The number of metastases: the 5-year survival of
      patients with 1, 2-3, > 3 hepatic nodules was 29, 21 and 17% respectively (p <
      0.05). 4) The extent of surgical resection: 5-year survival after minor and major
      resection was 28 and 18% respectively (p < 0.05). At multivariate analysis only
      stage of primary and percentage of hepatic replacement retained statistical
      significance. In 60% of 154 patients with recurrent disease the liver was again
      involved.

PMID- 7571047
TI  - Doxifluridine: an active agent in advanced gastrointestinal cancer.
AB  - BACKGROUND: The results of the use of chemotherapy in patients with advanced
      gastrointestinal malignancies have been disappointing. Complete responses are
      rare, and even partial responses are generally few with no benefit on survival.
      Since its introduction in clinical trials more than 30 years ago, fluorouracil
      has remained the most effective single agent in the treatment of these diseases.
      Doxifluridine is a new fluoropyrimidine derivative, that is converted into
      fluorouracil, its active component. Experimental data confirm cytotoxic
      selectivity for human tumor cells. METHODS: Three trials have been conducted at
      the Istituto Nazionale Tumori of Milan, to evaluate the tolerability and efficacy
      of doxifluridine administered endovenously or orally in patients affected by
      different gastrointestinal neoplasms. The data will be discussed. CONCLUSIONS:
      Our results indicate that doxifluridine may be superior to fluorouracil, the
      biochemical modulator as folinic acid seems to enhance its activity in colorectal
      patients. The oral schedule is feasible for home treatment.

PMID- 7571048
TI  - Intermediate biomarkers in the colorectal tumor progression.
AB  - Intermediate biomarkers are biological alterations in tissue which signal a stage
      of carcinogenesis between initiation and the development of a malignant tumor.
      Proliferation biomarkers are those that most satisfy the requisites for
      premorphological intermediate markers in the colorectal tumor progression. Cell
      proliferation changes in histologically normal intestinal mucosa are early events
      directly and closely associated with the morphogenesis of colorectal neoplasia.
      The transition from the morphological stage and the latter's further progression
      can be reliably monitored through the use of differentiation and genomic markers.
      In particular the incidence and the degree of DNA aneuploidy are indicators of
      the risk of malignant transformation in colorectal adenomas. New "regression
      related" biomarkers should be investigated for the planning of measures designed
      to bring about the regression of premalignant lesions.

PMID- 7571050
TI  - Screening for colon cancer in Germany.
AB  - Screening for colon cancer by fecal occult blood testing (Hemoccult) was started
      in Germany in 1977 as part of an annually offered cancer checkup. The results of
      the six years 1985-1990 are reviewed. Marked differences exist between male and
      female screenees regarding age and frequency of participation, test positivity
      and case finding rates. A total of some 1.500 colorectal cancers are traced
      annually in 4 million screenees. Test positivity and case finding rates depend in
      a characteristic pattern on the screening interval. A screening-out effect for
      colon cancer is evident in annually screened participants. Fecal occult blood
      testing has become part of the basic laboratory programme in the workup of
      patients in general medical practice. Compared to mass population screening, test
      positivity and case finding rates are higher, with positive predictive values 11%
      for cancer and 20% for large adenomatous polyps. CONCLUSIONS: Fecal occult blood
      testing is effective for screening and case finding of colon cancer. New tests
      specific for human hemoglobin could further improve this simple, inexpensive and
      generally available screening.

PMID- 7571049
TI  - Clinical implications of advances in the molecular genetics of colorectal cancer.
AB  - AIMS AND BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is the
      most common occurring hereditary form of colorectal cancer (CRC) where it
      accounts for as much as 10 percent of the total CRC burden. HNPCC is
      characterized by an autosomal dominant inherited predisposition to early age of
      onset (= 44 years) of CRC with proximal predominance (= 70% proximal to the
      splenic flecture) with an excess of synchronous and metachronous CRC (45% 10
      years after initial hemicolectomy or segmental resection as opposed to subtotal
      colectomy), features which characterize the Lynch syndrome I variant, while the
      Lynch syndrome II variant of HNPCC shows all of these features, but in addition,
      there is a marked excess of carcinoma of the endometrium, ovary, small bowel,
      stomach, pancreas, and transitional cell carcinoma of the ureter and renal
      pelvis, lesions which are integral to this syndrome. Because of the early onset,
      we recommend colonoscopy to be initiated at age 25 and repeated every other year
      through age 35 and then annually thereafter. Women need to undergo endometrial
      aspiration biopsy at the time of initial colonoscopy. METHODS AND RESULTS: Major
      advances in the molecular genetics of HNPCC have occurred during the past two
      years with identification of the hMSH2 gene at chromosome 2p and the hMLH1 gene
      at chromosome 3p, both of which have been cloned. PMS1 at chromosome 2p and PMS2
      2 at chromosome 7q have also been implicated in HNPCC's etiology. CONCLUSIONS:
      Genetic counseling is mandatory for presymptomatic DNA testing and for delivering
      information about the patient's germline status. Patients with germline mutations
      are offered prophylactic subtotal colectomy as an option to continued
      colonoscopy. It is now important for physicians to take careful cancer family
      histories so that this disorder can be readily identified, thereby enabling the
      initiation of highly targeted surveillance and management programs.

PMID- 7571051
TI  - Treatment and follow-up of large bowel adenoma.
AB  - The current clinical interest in large bowel adenoma is due to the evidence that
      most carcinomas arise in benign adenomas and therefore endoscopic removal of
      adenomas interrupts the sequence that leads to cancer. Colonoscopy is the best
      method for the detection and treatment of adenomas, with a diagnostic accuracy of
      94% and a low incidence of complications. The majority of polyps can be resected
      by snare polypectomy. Regarding small polyps, snare polypectomy without current
      application is recommendable and hot biopsy should be avoided owing to a non
      negligible risk of hemorrage. Though clinical significance of small polyps is
      controversial, in our experience and in other studies they have a potential for
      malignant progression (2.4% of adenomas containing invasive carcinoma are 6 mm or
      less in diameter) and those located in the rectosigmoid are predictive of
      proximal neoplasms. If endoscopic polypectomy significantly reduces the incidence
      of colorectal cancer, patients submitted to adenoma removal have an increased
      risk for metachronous adenomas. Surveillance is therefore mandatory, once the
      presence of synchronous adenomas has been ruled out (clean colon). Risk factors
      for adenoma recurrence are family history, age, size of adenoma, multiple
      adenomas, dysplasia, villous histotype. Holding in due consideration compliance,
      risk of complications, logistic problems and costs, the following guide-lines can
      be proposed: total colonoscopy at the time of endoscopic polypectomy (to obtain a
      "clean colon") and, in the case of unsatisfactory examination, within one year.
      first check at 3 years and, if negative, subsequent check at 5 years. for small
      tubular adenomas surveillance is indicated only in the case they are multiple.
      The evaluation of some intermediate bio-markers might contribute to the
      predictive determination of adenoma recurrence, with the goal to select groups of
      patients with the highest risk of recurrence of adenomas.

PMID- 7571052
TI  - Treatment of malignant polyps.
AB  - From 1975 to 1993, at the Division of Diagnostics and Endoscopic Surgery of the
      Istituto Nazionale Tumori in Milan, 191 malignant adenomas of colon-rectum have
      been endoscopically removed. On the basis of histopathologic criteria, endoscopic
      treatment has been judged adequate in 102 cases (53%), not adequate in 44 (23%),
      doubtfully adequate in 45 (24%). In 84 patients (44%) endoscopic polypectomy has
      been followed by surgical resection of the involved intestinal tract, 107
      patients (56%) have been treated only by endoscopy. Results have been evaluated
      on the basis of surgical specimen, clinical follow-up and survival, showing that
      criteria we have adopted for the adequacy of the endoscopic treatment have a high
      negative predictive value (96%) and a low positive predictive value (32%).
      Actuarial survival of patients treated only endoscopically is 97% at 5 years and
      95% at 10 years.

PMID- 7571054
TI  - Local excision of rectal tumours with transanal endoscopic microsurgery.
AB  - Transanal Endoscopic Microsurgery (TEM) is a novel technique, first introduced by
      Buess and coworkers in 1983 for the treatment of large sessile polyps of the
      rectum. Due to the excellent results the indication was then extended also for
      the removal of low risk early adenocarcinomas (pT1, G1-G2). TEM allows, by using
      an operative proctoscope of an outside diameter of only 4 cm., all the
      conventional surgical manoeuvers within the rectal lumen, up to 20 cm. from the
      anal verge. The Authors report a consecutive series of 53 patients submitted to
      TEM over a 37 month period; apart from 7 patients excluded for different reasons,
      postoperative diagnosis showed 30 adenocarcinomas (65.2%), 15 adenomas (32.6%)
      and 1 epidermoidal carcinoma (2.2%). The low recurrence rate observed both for
      adenomas (0%) and pT1 adenocarcinomas (9%) coupled with the optimum vision
      allowed by the 6-fold magnified stereoscopic view, make this technique the method
      of choice for selected patients with these kind of pathologies.

PMID- 7571053
TI  - Diet and chemoprevention of colorectal cancer.
AB  - There is copious evidence of the importance of diet in the causation of
      colorectal cancer. This comes from studies of populations, case-control studies,
      and prospective or cohort studies. The evidence from epidemiology is now
      beginning to treach a clear concensus that the disease is associated with high
      intakes of fat and meat and low intakes of cereal fibre, fruit and vegetables.
      There are various ways in which these observations are being applied to
      colorectal cancer prevention. These include dietary advice to populations and
      specific advice given to individuals at high risk of the disease.

PMID- 7571055
TI  - Improvement of colo-rectal cancer surgery following introduction of endoscopical
      approach.
AB  - In the period 1968-1993, we treated 399 patients for colo-rectal cancer. Up to
      1980, preceding large scale use of endoscopy, 217 patients, out of the group of
      399, were submitted to surgery; at time of diagnosis all patients had symptoms of
      advanced colonic tumor (intestinal obstruction; palpable mass; significant rectal
      bleeding); none of the lesions detected was in Dukes A or B1 groups; 56 patients
      were in Dukes B2 and stages C1 + C2 + D were detected in 161 cases. In period
      1981-1993 we treated 182 patients; in all cases the diagnosis consisted of
      endoscopical examinations. Out of this group 69 patients underwent endoscopic
      resection of polyps with focal neoplastic degeneration: 44 did not require
      surgery according to Haggitt criteria. In the group of 138 patients who underwent
      surgery, 89 were in Dukes A + B1 + B2 groups and 49 were in Dukes C1 + C2 + D
      groups. In our experience endoscopy is not essential in the clear cut colonic
      neoplasms, however it is an invaluable screening test in early stages, in poor
      symptomatic population, in elderly patients (> 50 y.o.) and in patients with non
      specific symptoms. We wish to emphasize how endoscopy has improved the results of
      colonic cancer surgery.

PMID- 7571056
TI  - Prognostic factors of rectum carcinoma--experience of the German Multicentre
      Study SGCRC. German Study Group Colo-Rectal Carcinoma.
AB  - A reliable evaluation of results of multimodal treatment requires the knowledge
      of the course of disease in patients treated by surgery alone and of the relevant
      prognostic factors. The data of a prospective multicentre observation study
      (Study Group Colo-Rectal Carcinoma, SGCRC) were analyzed by uni- and multivariate
      methods for the endpoints locoregional recurrence and observed overall survival.
      1121 patients with invasive rectum carcinomas are included. In 1056 (94.2%)
      patients the tumor was resected, 34 patients (3.0%) received postoperative
      adjuvant therapy, 61 patients (5.4%) preoperative and 25 (2.2%) pre- and
      postoperative radiation. The observed 5-year survival rate for R0 (no residual
      tumor) was 55% (95% confidence interval 52-58%), for R1 and R2 only 7% (3-11%).
      Following R0 resection the 5-year survival rates varied according to pT (74-24%)
      and pN (68-33%). The 5-year survival was 74% (68-80%) for stage I, 62% (56-68%)
      for stage II, 40% (35-45%) for stage III and 9% (0-21%) for stage IV. Stage III
      is prognostically inhomogeneous: pN1: 5-year survival 47% (39-55%), pN2, 3: 34%
      (27-41%) (p < 0.01). The rate of locoregional recurrence is influenced by tumor
      related factors (stage and tumor site) and treatment related factors. Local
      spillage of tumor cells, the treating institution and the individual surgeon are
      independent factors influencing locoregional recurrence. Between locoregional
      recurrence and observed 5-year survival exists a highly significant correlation.
      The most important tumor related prognostic factors following surgical treatment
      are residual tumor status (R classification) and anatomic extent as described by
      pTNM and stage grouping UICC). The treating institution as well as the individual
      surgeon are further independent "prognostic factors" which determine the
      frequency of locoregional recurrence and thus survival. In analysis of treatment
      results the institution and the surgeon should be considered, in studies on
      adjuvant treatment a stratification according to department and surgeon is
      needed.

PMID- 7571057
TI  - Surgical technique and colorectal cancer: impaction on local recurrence and
      survival.
AB  - The survival of patients with large bowel cancer continues to improve. This may
      be explained by an evolution in surgical technique for cancer resection. Survival
      statistics between 30% and 75% can be found for the same stage of disease by
      different surgeons and at different institutions. The absolute requirement for
      survival is a complete resection of cancer with free margins of dissection. The
      etiology of local recurrence was suggested to be spilled tumor cells from venous
      blood, trasected lymphatics or from tissue trauma at narrow margins of
      dissection. Blunt dissection technique may be responsible for an increased
      incidence of local recurrence and cancer related death especially in
      metastatically insufficient cancers. Although no touch technique may not be
      important, the wide dissection that it promotes is of benefit. Even if adjacent
      structures are involved, an anatomically disciplined en bloc sharp or
      electrosurgical dissection are the surgical techniques that are of paramount
      importance. Adjuvant intraperitoneal cytostatic agents may in the future be used
      to eliminate spilled tumor cells that may occur even though the surgical approach
      is optimized.

PMID- 7571058
TI  - Ras oncogene activation in benign and malignant colorectal tumours.
AB  - Activation of ras family genes has been implicated in colorectal tumourigenesis.
      K-ras is the most frequently altered gene in colorectal neoplasias. The major
      activating mechanism involves point mutations, although recent data have shown a
      more complex role, through qualitative alterations. The incidence of codon 12
      mutations in K-ras and N-ras genes in patients with primary colorectal
      adenocarcinomas was examined. We employed a non radioactive PCR-RFLP assay for
      the detection of mutant samples. We found a significant K-ras activation at codon
      12 (38%), while the incidence of N-ras codon 12 activation was limited to 1.5%.
      These results are in agreement with previous reports. Association has been
      investigated with clinical and histopathological parameters. Point mutations
      appear to be more frequent in carcinomas with elements indicating a development
      from adenoma, in ages below 50 years, in females who had the tumor located at the
      rest of the large bowel in comparison with rectosigmoid and in higher grade of
      differentiation.

PMID- 7571059
TI  - Preoperative radio-chemotherapy response as prognostic factor in colorectal
      cancer.
AB  - In order to demonstrate if radiotherapy (RT) is able to reduce the number of
      local recurrences and to increase the survival rate of patients (pts) with
      colorectal cancer, the authors are participating in a large randomized
      international trial with the goal of comparing patients treated with preoperative
      radiotherapy plus surgery and patients treated only by surgery. The authors
      noticed that some patients treated with preoperative radiotherapy showed a
      reduction in tumor size at the time of endorectal ultrasonography. The authors
      considered the incidence of recurrences in patients responsive to radiotherapy
      (RT responsive group), in patients non responsive to radiotherapy (RT non
      responsive group) and in patients not treated with radiotherapy (no RT group)
      with the aim of establishing if the responsiveness to preoperative radiotherapy
      could be considered a prognostic factor in colorectal cancer. After a three year
      follow-up RT responsive group (41 pts) showed no recurrences (0%); RT non
      responsive group (27 pts) showed 7 (25%) recurrences; no RT group (66 pts) showed
      27 (41%) recurrences. Our data indicates that responsiveness to preoperative RT
      can be considered a prognostic factor. A large number of patients is required to
      confirm this observation.

PMID- 7571060
TI  - Radiotherapy and combined chemo-radiotherapy of rectal cancer.
AB  - During the last twenty years radiotherapy has been more frequently integrated
      with conventional demolitive surgery of rectal cancers because radical surgery,
      the treatment of choice of these tumors, has achieved a plateau of therapeutic
      results in the various stages of disease. The incidence of pelvic failures in
      stages B2 and C remains high, despite apparently complete resections. Disease
      free interval, quality of life and survival are negatively affected. Radiotherapy
      at doses of about 50 Gy is able to destroy subclinical foci of disease after
      surgery (post-operative radiotherapy) or to reduce volume and infiltration of a
      locally extended tumor facilitating surgery (pre-operative radiotherapy).
      Moreover, radiotherapy proved to be effective in the treatment of pelvic
      recurrences. The great improvement of radiotherapeutic techniques in the last
      decade allows treatments at high doses to the target, minimizing the risk of side
      effects to contiguous normal tissues. A large number of clinical studies seems to
      demonstrate that the efficacy of radiotherapy is enhanced by combining
      chemotherapy both in the pre-operative approach and in the post-operative
      adjuvant treatment. To date, no definitive agreement about the optimal schedules
      of combined chemo-radiotherapy has been achieved. Many controlled studies are in
      progress investigating the most effective schedules with the minimal toxicity.
      The main indications of radiotherapy in the treatment of rectal cancer are here
      synthetically presented. Pros and cons of each approach are illustrated according
      to updated reports. For wider information on this topic of great interest and in
      progress the consultation of some reviews is suggested (1, 3, 23).

PMID- 7571061
TI  - Immunodiagnosis and immunotherapy of isolated tumor cells disseminated to bone
      marrow of patients with colorectal cancer.
AB  - Micrometastatic spread of viable carcinoma cells is thought to be the leading
      cause of death in patients with completely resectable colorectal cancer. Since
      this minimal spread is missed by current tumor staging procedures,
      immunocytochemistry with monoclonal antibodies to epithelial cytokeratins have
      been successfully applied to detect individual carcinoma cells disseminated to
      mesenchymal organs such as bone marrow. Although the skeleton is not a
      preferential site of overt metastases in colon cancer, individual cytokeratin
      positive tumor cells in bone marrow can be detected in about 30% of patients with
      no clinical signs of overt metastases (stage MO). The presence of these cells in
      bone marrow at the time of primary surgery turned out to be a strong independent
      indicator for subsequent relapse in organs such as liver and lungs. In a
      randomized, multicenter trial it could be furthermore demonstrated that the
      intravenous administration of the monoclonal antibody 17-1A into patients with
      Dukes C colon cancer significantly reduced the overall death rate by 30% and
      decreased the recurrence rate by 27%, thus underscoring the accessibility of
      micrometastatic tumor cells for immunotherapy. The present article reviews the
      current state of immunologic strategies used to detect, characterize, and treat
      minimal residual colon cancer.

PMID- 7571062
TI  - Immunological controls of postoperative infections in colorectal tumours.

PMID- 7571063
TI  - The use of drains in elective surgery for colorectal cancer: always, never or
      selectively?
AB  - Indications for the use of drains of the peritoneal and pelvic cavity following
      elective surgery for colorectal cancer provide a source of continuing
      controversy. Analysis of the experimental and clinical studies indicates that
      routine drainage in needless with standard elective surgery for colon cancer.
      Some risk factors justify the selective use of drains when there is an increased
      risk of postoperative morbidity. In contrast, surgery for rectal cancer is
      associated with high risk of wound site complications and usually requires
      drainage with or without the filling of a pelvic "dead space" with well
      vascularized soft tissues.

PMID- 7571064
TI  - Radioimmunoguided surgery: clinical experience with different monoclonal
      antibodies and methods.
AB  - The intraoperative detection of tumors by means of a gamma-ray detector that
      recognized radiolabelled monoclonal antibodies (MoAbs) on tumour cell surfaces
      has been shown to be feasible and clinically useful. The technology is called the
      Radioimmunoguided Surgery (RIGS) system. We have been working with this system
      for five years and in this paper we report our experience using different
      radiolabelled MoAbs and methods in terms of clinical utility in patients with
      primary or recurrent colorectal cancer. In the first part of the experience we
      injected with the MoAb B72.3 a group of 66 patients with primary (36) or
      recurrent (30) cancer introducing for 7 out of 66 a variation of the method to
      try to overcome some limits of the original procedure. With the new method, based
      on the avidin-biotin binding, it is possible to use anti-Cea MoAbs and to reduce
      the preoperative waiting time, injecting biotinylated MoAbs and avidin. In the
      second part of the experience, a second group of 15 patients with primary (12)
      and recurrent (3) cancer was injected with biotinylated MoAbs FO23C5 (anti-Cea)
      while in a third group of 16 patients, 6 with primary and 10 with recurrent
      cancer a cocktail of antibodies was used. During surgery a probe (NEOPROBE) was
      used to count obvious tumor, surrounding normal tissue and to scan the abdomen
      for areas of increased radioactivity. In the first group of patients tumour was
      localized by probe in 18/36 (50%) cases of primary cancer and in 24 out of 30
      recurrences (80%). In the second group tumour was localized in 8/12 (67%) primary
      cancers and in 2 out of 3 (67%) recurrences. In the last group primary tumours
      were localized in 5/6 (83%) patients and recurrent cancer in 7/10 (70%). The
      method altered the surgical procedure in 2 out of 36 primary tumours (6%) and in
      8 out of 30 recurrences (27%) injected with the B72.3. In the group of 15
      patients injected with the anti-Cea the method changed the surgical strategy in
      2/12 (16%) primaries and in 1 out of 3 recurrences. We had no real clinical
      utility in the primary cancers injected with cocktails but in 4 out of 10 (40%)
      patients with recurrent cancer it was possible to localize occult metastatic
      tissue. In conclusion, the sensitivity of the different MoAbs is similar in the
      groups even though it is noted that B72.3 seems to be more indicated in recurrent
      cancers and the FO23C5 in primary tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571065
TI  - [Department of the molecular bases of semiotics].
AB  - Department of molecular basis of semiotics was organized in 1986. The main task
      of the department was to work out new approaches in estimation of the state of
      immune and blood system at the tissue, cell and molecular levels, using
      biochemical, biophysical and molecular biology techniques. There are several main
      directions of scientific investigations at the department. Most informational
      methods were collected in "immunological portrait" for differential diagnostic
      and complex investigation of the immune system of autoimmune patients. This group
      of techniques was used to study changes in the immune system of Kievites after
      the Chernobyl disaster. A decrease of complement and thymic serum activity was
      detected. Antibodies against nuclear components appeared in 20% of donors. And a
      higher of circulating immune complex of low molecular weight was observed. Low
      level of thymic serum activity in blood of autoimmune patients with rheumatoid
      arthritis, lupus erythematosus, diabetes, herpes and other depends on the
      appearance of zinc-independent timuline inhibitor less then 2000 D. Another kind
      of thymic hormone inhibitors was detected in thymectomized adult mice. Its effect
      disappears when zinc added in blood rather due to competition for lymphocyte
      surface receptors timuline and its inactive analogue than other mechanism.
      Therapeutic effect of UV irradiation of patients' blood was shown to be closely
      connected with the changes in thymic serum activity in respect to stabilization
      of thymic hormone/inhibitor ratio. The immunochemical techniques were used to
      detect and investigate tumor-associated chromatin antigens in human and animal
      tumor cells. Antigens not found in normal tissues were detected when using rabbit
      antibodies against chromatin of rat hepatocarcinoma and human colon and
      carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571067
TI  - [Department of lipid biochemistry].
AB  - The Department of Lipid Biochemistry was organized at the end of 1980. The head
      of the Department is Dr. Nadiya M. Gula, the Corresponding Member of the National
      Academy of Sciences of Ukraine, Dr. N. m Govseeva and Dr. U. M. Klimashevsky work
      at the Department from the very beginning of its existense. Doctors G. L. Volkov,
      I. P. Artemenko, D. I. Balkov, O. O. Melnik and O. F. Perederiy worked here at
      different time. Two young scientists T. N. Goridko and V. M. Margitich recently
      began to work at the Department of Lipid Biochemistry. At present the main
      research interests in the Department of Lipid Biochemistry are focused on the
      functional role of phospholipids and some unusual lipids, on membrane-associated
      lipid dependent properties of cell (neuroblastoma cell, spermatozoa, some other
      types of cells), on membrane lipid peroxidation. For the last five years we have
      been working mainly with the murine neuroblastoma C1300 cell and some other types
      of cells in order to clarify the role of "unusual" minor cell lipids--N
      acylphosphatidylethanol amine (NAPE) and N-acylethanolamine (NAE). NAPE and NAE
      were found for the first time in mammalian tissues by H. H. Schmid and coworkers.
      They observed an accumulation of unusual lipids in the infarcted areas of canine
      myocardium after coronary artery ligation and have suggested that they may be
      generated as protective agents aimed at minimizing irreversible ischemic injury
      and infarct size. We have detected unusual minor phospholipid NAPE in the cells
      of murine neuroblastoma and identified it by sequential chemical
      degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571066
TI  - [Department of molecular immunology].
AB  - The Department of Molecular Immunology was created at the Institute in 1982. It
      was founded by S. V. Komissarenko, a pupil of the well-known Ukrainian biochemist
      M. F. Guly. Today, S. V. Komissarenko is the Academician of Ukrainian National
      Academy of Sciences and one of the leading specialists in the field of Molecular
      Immunology. The main scientific problems studied at the Department now are
      molecular mechanisms of the immune recognition, antigenic structures of proteins
      and peptides as well as the mechanisms of lymphocyte activation underlying their
      proliferation and differentiation. Over the last years, special attention was
      payed to developing the approaches of immunochemical analysis of certain proteins
      and peptides of blood coagulation system to control thrombus formation. The
      results of these investigations are to be used for designing the immunodiagnostic
      test-systems and for creating synthetic vaccines for clinical practice.

PMID- 7571068
TI  - [Interdepartmental division of functional biochemistry].
AB  - The Department of Functional Biochemistry was organized at the Institute of
      Biochemistry of the National Academy of Sciences of Ukraine in 1990. Since that
      time the collaborators of the Department develop the aldehyde hypothesis of
      pathogenesis of chronic alcoholism and new high effective methods of its
      treatment; they have found certain adaptation mechanisms arising in the organism
      under stress states and pathogenetic mechanisms of formation and development of
      the radiation encephalopathy in victims of the accident at the Chernobyl NPP. The
      department researchers have published 92 works.

PMID- 7571069
TI  - [Laboratory of transport ATPases].
AB  - The laboratory of transport ATPases was founded in 1982 with the purpose of
      raising the effectiveness of fundamental researches in the field of membranology
      and bioenergetics. The investigations directed to elucidation of the regulatory
      mechanisms of one of the key ion-transporting cell systems--Na+, K(+)-ATPase,
      have been conducted for this period. The regulatory role of Mg and Ca ions in the
      process of functioning of this membrane-bound enzyme is investigated in detail.
      It is established that the process of Na+, K(+)-ATPase inhibition with Mg-ions is
      combined and accompanied with the competition with Na+ for its binding sites,
      indirect influence on K-sites and relaxation of the intersubunit interactions. Ca
      ions are the next effective modulators of the enzyme catalytic activity and
      sensitivity to the specific inhibitor ouabain. Great attention was also focused
      in the laboratory on the employment of detergents as effective tools for the
      investigation of biomembrane, that made it possible not only to solubilize
      different membrane components, to study their protein and lipid composition but
      also to purify the integral membrane proteins, such as Na+, K(+)-ATPase, in
      functionally active state and study their structural and functional relationships
      in detail. Thus, the large amount of experimental data on the use of detergents
      for the purification of Na+, K(+)-ATPase and elucidation of the mechanisms of its
      functioning was obtained. Since 1987 the investigations of the catalytic
      properties of Na+, K(+)-ATPase isozymes had been conducting in the
      laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571070
TI  - [Department of biochemistry of coenzymes].
AB  - One of the leading trends in the fundamental researches which A. V. Palladin
      Institute of Biochemistry of the National Academy of Sciences of Ukraine had been
      performing from the moment of its foundation in 1925 is vitamins biochemistry.
      This resulted in establishing of one of the guiding experimental centers in the
      field of fundamental biochemistry within the former USSR.

PMID- 7571071
TI  - [Laboratory of technology of biopreparations].
AB  - The main scientific direction of the Laboratory is the development of new
      biochemical technologies for obtaining various biopreparations based on animal
      and plant raw materials, especially on that of the sea organisms. Fundamental
      investigations of the preparations of animal and microorganism hydrolysis have
      enabled the researchers to develop technologies for obtaining Str. griseus and
      Ceph. acremonium proteolytic complexes and to study their properties for the
      latter could be used as reagents in chemistry of proteins. Immobilized polyenzyme
      systems of proteases with silicagel and activated carbon fibre material as a
      matrix were created on the basis of investigations of immobilized enzymes. The
      advantages of immobilized biocatalysts possessing highest stability and a
      possibility of repeated application are described. Biotechnological isolation of
      bioactive preparations (BAP) of lipid-protein nature that are the structure
      components of cells membranes is the key problem at present. Biochemical
      principles of BAP metabolisms regulation in cell membranes and the role of the
      obtained biopreparations in correction of pathological conditions are also
      studied. These investigations promoted development of technologies for two new
      biopreparations from sea organisms (Calmar's gonades) for medicine. The first one
      is a set of surface active phospholipids and the second one is a set of
      nucleopeptides affecting the secretion of sex hormones. It has been found that
      surface active preparations show an antioxidative and membrane-stabilizing
      properties as well. It has also been shown that the preparation corrects the
      effect of pathology conditions in case of experimental hepatitis-induced by CCl4.
      The preparation influences the antioxidative system and thus the rate of lipid
      peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571072
TI  - [Department of sterol biochemistry].
AB  - The Department of Steroid Biochemistry headed by Professor Vendt Volodymir
      Petrovich, Doctor of Biological Sciences (1906-1993) was created on the basis of
      the Department of Photobiochemistry in 1976. At that time the Department was
      headed by Kokunin Vasyl Andriyovich, Candidate of biological sciences, till 1990.
      Professor Yu.D.Kholodovais, Doctor of biological sciences, is the head of the
      department today. Study of action mechanism of low-molecular-weight biologically
      active substances of steroid nature (cholesterol, cholecalciferol, ecdysterone)
      under normal and pathological conditions (atherosclerosis, rickets) as well as
      the development of scientific grounds of production of new drugs used both in
      medicine and agriculture are the basic purposes of the Department. The department
      is engaged in: 1) the study of biosynthetic processes of de novo cholesterol and
      its precursors in different tissues and cells of the organism; 2) the elucidation
      of the role of sterols as the components of membrane structure in different cells
      as well as the study of cholesterol absorption processes in the intestine and the
      search of a hypocholesterolemic agents; 3) the study of localization and
      biological properties of vitamin D-dependent proteins in order to elucidate their
      role in intestinal calcium transport; 4) the investigation of different classes
      of blood plasma composition of intestine and liver lipoproteins (LP), their
      structural, functional properties and frequency of occurrence; 5) the search of
      highly effective biostimulators of steroid nature, the elucidation of their
      action mechanisms and elaboration of new preparations on their basis for medicine
      and agriculture. Sterols are components of lipids with
      cyclopentanoperhydrofenantren molecular structure. Cholesterol is the basic
      animal and human organism sterol. A new complicated, multi-step method of
      cholesterol biosynthesis and participation of a number of enzymes and cofactors
      in it have been studied (V. Vendt, R. Morozova, I. Nikolenko, Visnyk AN URSR,
      1978). Cholesterol is the major component of cell membrane structures which
      determines their structure and permeability. The interest to study a new method
      of cholesterol biosynthesis regulation arises from the reason that cholesterol
      pools in membranes participate in such diseases as rachitis, atherosclerosis,
      arterial coronal disease, different forms of cholecystitis, etc. It is
      established that the nature, rate and intensity of de novo cholesterol
      biosynthesis depend on types of cells, tissues and organs, taking into account
      the functional state of final compounds in these biosystems under normal
      conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571073
TI  - [Laboratory of medical biochemistry].
AB  - The main research directions of the laboratory: investigation of infringement
      mechanisms in certain metabolic processes with vitamin D3 deficiency and ways of
      their regulation; study of mechanisms of vitamin D3 functioning and exchange in
      organisms in the healthy state and with certain pathologies; elaboration of high
      effective preparation forms of vitamin D3 for their implementation in medicine
      and agriculture. It is proved that a decrease in content of active metabolites of
      vitamin D3 in case of rickets depends on the process gravity; disturbances in the
      mineral exchange and formation of cyclic nucleotides, changes in the structure
      and conformation of the blood plasma proteins, lipoproteins of low and high
      density, lipids and cellular membrane proteins (especially protein 3 of
      erythrocyte membranes) are observed. This causes the disturbances in vitamin D3
      function and in activity of membrane-bound enzymes. The above mentioned changes
      and the increase of the atherogenicity coefficient allowed a conclusion to be
      made that rickets of children is the risk-factor of cardiovascular diseases both
      in childhood and in the following age periods. It is determined that when the
      organism is provided with vitamin D3 the latter is transported not only into
      hepatocytes but also into reticulocytes which are a locus for vitamin D storage.
      This factor maintains the concentration of active metabolites of vitamin D3 on
      the physiological level within three months. The provision degree of the fetus
      and the newborn infants depends on mother's concentration level. However the
      vitamin D3 exchange varies during the pregnancy period.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7571075
TI  - [Department of chemical kinetics].
AB  - Department of Biochemical Kinetics (headed by Kosterin S. A., Doctor of
      Biological Sciences) was founded in 1988. Research activity of the Department is
      mostly concerned with the biochemical mechanisms and dynamics of Ca2+ exchange in
      the smooth muscles, particular emphasis being laid on the examination of kinetic
      and catalytic properties of the membrane-linked energy-dependent Ca2+
      transporting systems involved in regulation of intracellular Ca2+ concentration
      and control of the contractile behaviour of the smooth muscle cells. At present,
      the staff of the Department includes 2 doctors of sciences, 9 candidates of
      sciences and 6 technicians. Experimental data obtained at the Department since
      the date of its foundation provide new information concerning the energy
      dependent Ca+ transporting systems of the smooth muscle cells, show the important
      role of Ca2+ pump of plasma membrane, endoplasmic reticulum and mitochondria as
      well as Na(+)-Ca2+ and Ca(2+)-H+ exchangers of sarcolemma in the regulation of
      Ca(2+)-exchange and mechanical activity of the smooth muscle. In the experiments
      performed on the inside-out vesicles derived from the sarcolemma of the
      myometrium the effect of quasi-stationary K(+)-diffusional membrane potential
      ("K(+)-valinomycin system") on the Mg2+, ATP-dependent Ca2+ transport was
      studied. It has been proved that the membrane potential (negative inside)
      stimulated the Mg2+, ATP-dependent transsarcolemmal transport of Ca2+ in the
      myometrium. The membrane potential stimulate maximal velocity of the Ca2+ pump
      leaving the affinity constant to the bivalent cation unaltered.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571074
TI  - [Department of the Biochemistry of Muscles].
AB  - The basic scientific achievements of the Department of Biochemistry of Muscles
      organized at the Academy of Sciences of Ukrainian SSR in 1944 are presented in
      this short historical overview. The basic guidelines for activities in the
      scientific field are as follows: study of biochemical processes in the working
      muscles as well as during misfunctions and disabilities, processes of adenine
      nucleotides exchange and ammonia creation, biochemical characterization of Ca2+
      and H+ transport through the plasma and sarcoplasmic reticulum membranes. It is
      shown that creatine and creatine phosphate as well as adenine nucleotide content
      and metabolism affect the muscle functioning, glycogen metabolism proceeds
      simultaneously with the lowering of content of inorganic phosphate. The facts of
      glucose phosphorylation and its conversion via glycolytic pathways and the
      backward reaction of glycolysis (the aerobic synthesis of phosphopyruvate,
      glycogen synthesis from glucose in the presence of phosphorylase) were
      determined. After the muscle work up to tiredness adenine nucleotide depletion is
      not limited by its dephosphorylation, but goes up to formation of inosine acid
      and ammonia. Deamidation is shown to be in myofibrillar fraction and in
      sarcoplasmic reticulum of the skeletal muscle. Deamidation activity is not
      registered in myocardium myofibrillar fraction but it is registered in
      sarcoplasmic reticulum. AMP-phosphohydrolase and adenosine desaminase were found
      in membranes of the sarcoplasmic reticulum. The decrease in activity of all
      enzymes mentioned above is registered during myocardium hypertrophy, because of
      aorta narrowing. These data permit creating the methods for obtaining substance
      "adenosine phosphate" for treatment of cardiac pathologies. Glutaminase was found
      to be active in the muscles. This activity depended on the organism functioning.
      The ammonia usage by the muscle cells goes with glutamine synthesis and
      consumption of energy of ATP, e.g. protein amidation. The later is of all
      biological significance and is used in the fields of medicine actualls concerned
      with the following fact: the velocity of hydrolysis of amidated protein is
      different for such pathology as epilepsia, tuberculosis, poisoning with manganese
      oxides. The methods for diagnostics of the above pathological states were
      developed on this basis. It is proved that glutamine nitrogen can be also used in
      the reaction of transamination, particularly during synthesis of purines, inosine
      acid and it is stored in a form of glutaminic acid. Changes in carbohydrate and
      phosphorus metabolism, in nitrogen and energetic exchanges and mitochondria
      overfilling with calcium were determined under E-avitaminosis dystrophy.(ABSTRACT
      TRUNCATED)

PMID- 7571076
TI  - [Department of metabolism regulation. Biochemistry problems].
AB  - The publication represents main results of investigations, performed at the
      Department of Metabolism Regulation in 1950-1995. The problems of protein
      biosynthesis, fixation and the regulatory role of carboxylic acid in
      heterotrophic organisms were studied. The role of formic acid in metabolism and
      changes in metabolic processes at chronic alcoholism were investigated as well.
      The fundamental results were used as a basis for the solution of practical
      questions of medicine and animal husbandry.

PMID- 7571078
TI  - [Role of low molecular weight metabolites as natural regulators of metabolism].
AB  - The paper presents results of scientific activity of the Department of Metabolism
      Regulation. The main sections are: carbamates formation and their role in
      metabolism regulation; metabolic system of acid-base homeostasis in animals;
      polyamines metabolism in the extremal states; mechanisms of metabolic adaptation
      in mammals. Experimental data are presented which evidence for the fact that
      tissue proteins in vivo are subjected to nonenzymic carboxylation with formation
      of carbominic groups. In this case a charge variation in definite sites of
      protein molecule is observed, which specifies variation of the protein
      conformation and biological properties. Basic regularities of protein carbamate
      formation reactions are revealed with factors affecting their intensity. It is
      shown that the presence of carbonic acid in the medium increases the rate of
      reactions catalyzed with lactate dehydrogenase from the rabbit liver, glucose-6
      phosphate dehydrogenase from yeast and trypsin. Under the same conditions the
      reaction velocity rate catalyzed with glucose-6-phosphate dehydrogenase from the
      rabbit liver and with ATP-citrate (pro-35)-liase is considerably decreased.
      Changes in the concentration of carbonic acid within the physiological limits are
      found to have no effect on lactate dehydrogenase from the cattle heart and
      chymotrypsin. The rate of the reaction catalyzed by NAD-dependent malate
      denydrogenase was studied as affected by carbon dioxide. It is shown that
      acceleration of the catalysis in these systems depends on the presence of both a
      bicarbonate anion and soluble carbon dioxide. IR spectra of NAD-dependent malate
      dehydrogenase in the deuterium oxide solutions were studied in the CO2-free
      solutions and solutions saturated with it.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571077
TI  - [Department of neurochemistry].
AB  - By the beginning of 1980s the questions concerning the mechanism of
      neurosecretion, the mode of neurotoxin action on this process and the mechanism
      of protein insertion into biological membranes were the principal directions of
      studies. Two views on the process of insertion of membrane proteins into, and
      transport across the biological membranes have been proposed. One hypothesis on
      membrane biogenesis describes the mechanism of incorporation of protein molecules
      into phospholipid matrix as a co-translational process. It starts with the
      synthesis of a hydrophobic N-terminal signal sequence of the protein destined to
      span the bilayer. In this case the energy of elongation was supposed to be
      utilized for insertion of the protein into hydrophobic core of the bilayer. Using
      the model system of co-translational translocation that consisted of liposomes
      and cell-free translational system including wheat germ extract and poly(A) RNA
      obtained from the mammary gland it has been studied whether the liposomes could
      serve as acceptor of synthesized secretory proteins. It is shown that in the
      presence of casein mRNA the 14-C-labeled product of translation is accumulated
      inside liposomes. When mRNA for globin, a nonsecretory protein, is translated in
      this cell-free system, 14-C-label is not found in the internal volume of
      liposomes. The polypeptides extracted from liposomes after their incubation in
      the system of casein mRNA translation interact specifically with anti-casein
      antibodies (D. I. Balkov, A. V. El'skaya, V. K. Lishko et al., 1988). These data
      provide the evidence that the transfer of synthesizing casein through bilayer
      lipid membrane does not require a specific receptor. Insertion and transfer of
      this protein occur co-translationally, due to the interaction of "signal peptide"
      with membrane lipids. The second model of the assembly of protein into membrane
      supposes an ability of hydrophilic proteins to cooperate with the phospholipid
      bilayer. As a result of such cooperation the polypeptide changes its conformation
      adequately to the hydrophilic environment and is integrated with the bilayer.
      This second model suggests the existence of water soluble precursors of membrane
      proteins localized in the cell cytoplasm. The last idea was studied in experiment
      with a specific hydrophilic protein from the cytoplasmic fraction of excitable
      tissues. Tetrodotoxin-sensitive (TTX-sensitive) structures have been found in
      soluble fractions of the brain, heart and skeletal muscle homogenates (V. K.
      Lishko, M. K. Malysheva, A. V. Stefanov, 1977). Initially we prepared
      proteoliposomes by sonication of a phospholipid suspension with the supernatants
      of tissue homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571079
TI  - [Division of regulatory cellular systems (Lvov)].
AB  - Two departments of the A. V. Palladin Institute of Biochemistry of the National
      Academy of Sciences of Ukraine were founded in 1969 in Lviv. These were: the
      Department of Biochemistry of Cell Differentiation headed by Professor S. I.
      Kusen and Department of Regulation of Cellular Synthesis of Low Molecular Weight
      Compounds headed by Professor G. M. Shavlovsky. The Lviv Division of the A. V.
      Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine
      with Professor S. I. Kusen as its chief, was founded in 1974 on the basis of
      these departments and the Laboratory of Modelling of Regulatory Cellular Systems
      headed by Professor M. P. Derkach. The above mentioned laboratory which was not
      the structural unit obtained the status of Structural Laboratory of Cellular
      Biophysics in 1982 and was headed by O. A. Goida, Candidate of biological
      sciences. From 1983 the Laboratory of Correcting Therapy of Malignant Tumors and
      Hemoblastoses at the Institute of Molecular Biology and Genetics, Academy of
      Sciences of Ukraine (Chief--S. V. Ivasivka, Candidate of medical sciences) was
      included in the structure of the Division. That Laboratory was soon transformed
      into the Department of Carbohydrate Metabolism Regulation headed by Professor I.
      D. Holovatsky. In 1988 this Department was renamed into the Department of
      Glycoprotein Biochemistry and headed by M. D. Lutsik, Doctor of biological
      sciences. In 1982 one more Laboratory of Biochemical Genetics was founded at the
      Department of Regulation of Cellular Synthesis of Low Molecular Weight Compounds,
      in 1988 it was transformed into the Department of Biochemical Genetics (Chief-
      Professor A. A. Sibirny). In 1989 the Laboratory of Anion Transport was taken
      from A. V. Palladin Institute of Biochemistry, Academy of Sciences of Ukraine to
      Lviv Division of this Institute. This laboratory was headed by Professor M. M.
      Veliky. One more reorganization in the Division structure took place in 1994. The
      Department of Glycoprotein Biochemistry (Chief--M. D. Lutsik, Doctor of
      biological sciences) was renamed the laboratory and a new Department of
      Regulation of Cellular Proliferation headed by R. S. Stoika, Doctor of biological
      sciences, was founded. Since 1992 the Division has its present name and exists as
      an independent research institution with the rights of the Institute of the
      National Academy of Sciences of Ukraine. At present about 100 researchers work at
      the Division, among them there are 8 Doctors and 27 Candidates of biological
      sciences. For the period of the Division existence 6 doctor's theses and 30
      candidate theses were defended.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571080
TI  - Pigments of the gastrointestinal tract: a comparison of light microscopic and
      electron microscopic findings.
AB  - It is now apparent that light microscopy and histochemistry failed to identify
      correctly the nature and composition of pigments in various gastrointestinal
      tract melanoses. In most instances it was thought that the pigment was melanin or
      a melanin-like substance. Electron microscopy (EM) and electron-probe energy
      dispersive x-ray analysis have rectified these errors and have shown the
      following: in melanosis coli the pigment granules contain lipofuscin; in
      melanoses ilei the pigment granules may contain either silicates and titanium or
      hemosiderin; and in melanosis duodeni the pigment granules contain iron sulfide.
      In melanosis esophagi it is not clear what the pigment is; it could be melanin or
      lipofuscin.

PMID- 7571081
TI  - Role of apoptosis in biology and pathology: resistance to apoptosis in colon
      carcinogenesis.
AB  - The overview of apoptosis presented here emphasizes cell deletion in the immune
      system, with particular reference to T- and B-lymphocyte development, and the in
      vivo and in vitro senescence of human neutrophils. Some biochemical criteria that
      are used to identify apoptotic cells are described. Pitfalls in using agarose gel
      electrophoresis as the sole method for the identification of apoptotic cells are
      discussed. There are multiple modes of cell death that can be identified at the
      morphologic level. Thus the central role of microscopic methods, and in
      particular, electron microscopy, as an important tool in the study of cell death
      mechanisms, is presented. Apoptosis has a protective role against disease and
      could, a priori, have an important role in either the initiation or progression
      of cancer. Two paradoxes concerning the relationship of tumor aggressiveness at
      the clinical level to mitotic activity have been explained by an evaluation of
      apoptotic index. In the first case, basal cell carcinomas grow slowly but show a
      high rate of mitosis. Here, the apoptotic rate is quite high, but just below the
      mitotic rate, thereby accounting for the slow rate of growth. A second instance
      is follicular lymphoma, which has a low rate of mitosis that is less than that
      described for reactive germinal centers. However, apoptosis is markedly reduced
      in follicular lymphomas compared with that seen in reactive germinal centers,
      thus providing an explanation for the progressive growth of the follicle. We
      present a brief description of recent work from our laboratory that indicates
      that apoptosis may play an important role in colon carcinogenesis. We have shown
      that sodium deoxycholate, the particular bile salt present in highest
      concentration in the colon, induces apoptosis in the goblet cells of the human
      colonic mucosa in an in vitro assay. The intriguing finding is that cells of the
      normal-appearing mucosa of colon cancer patients are resistant to bile salt
      induced apoptosis. This suggests a novel hypothesis about the etiologic role of
      bile salts in colon cancer. The chronic presence of bile salts that accompany a
      high-fat diet could select for apoptosis-resistant epithelial cells in the colon
      over time. Thus, a resistance-to-apoptosis bioassay may prove useful as an
      intermediate biomarker for determining which individuals are at high risk for
      colon cancer.

PMID- 7571082
TI  - Sarcomatoid carcinoma: an ultrastructural study with light microscopic and
      immunohistochemical correlation of 10 cases from various anatomic sites.
AB  - The histogenesis of sarcomatoid carcinoma has been an intriguing topic for
      pathologists for many years, and considerable evidence has accumulated in the
      fields of tissue culture, electron microscopy, and immunohistochemistry to
      support the concept that the sarcomatous cells derive by way of "divergent
      differentiation" (metaplasia) from the carcinomatous elements. We have studied a
      group of 10 cases of these tumors from various organs, using detailed
      ultrastructural analysis as well as light microscopic and immunohistochemical
      correlation. We found that there is an ultrastructural spectrum of
      differentiation from epithelial to mesenchymal type features and that the
      malignant spindle cells may be purely epithelial (3 cases), purely mesenchymal (3
      cases), or a mixture of both (4 cases). Furthermore, individual cells may show
      biphasia, having desmosomes and tonofibrils as well as well developed rough
      endoplasmic reticulum and filaments with dense bodies. Electron microscopic and
      immunohistochemical results do not always correlate, illustrating the prudence of
      using several keratin antibodies, including wide-spectrum ones, and of performing
      electron microscopic examination on these tumors.

PMID- 7571085
TI  - Primary intraoral epithelioid hemangioendothelioma presenting in childhood:
      review of the literature and case report.
AB  - Epithelioid hemangioendothelioma (EH) is a recently described vascular neoplasm
      of borderline or intermediate malignant potential. This tumor arises from medium-
      to large-sized vessels, primarily involves the soft tissues of the extremities as
      well as the liver and lung, and rarely occurs in the head and neck region. Only
      eight well-documented cases of intraoral EH have been reported. We present an
      additional pediatric case of EH confined to the oral cavity and review the
      literature regarding EH presenting as an intraoral mass. EH is characterized
      histopathologically as an epithelioid lesion arranged in nests, strands, and
      trabecular patterns with infrequent vascular spaces. Occasional erythrocytes
      within intracytoplasmic lumina may be seen in tumor cells. Ultrastructural
      examination typically shows intracytoplasmic lumina with pseudopodial cellular
      membrane extensions. The cytoplasm usually contains intermediate filaments
      infrequently associated with Weibel-Palade bodies. Neoplastic cells are
      immunoreactive for factor VIIIR:Ag and Ulex europaeus. Histopathologic features,
      which may be associated with aggressive clinical behavior, include significant
      cellular atypia, one or more mitoses per 10 high-power fields, an increased
      proportion of spindled cells, focal necrosis, and metaplastic bone formation.
      Because of the intermediate malignant potential of epithelioid
      hemangioendothelioma, complete tumor resection is recommended for intraoral
      lesions.

PMID- 7571084
TI  - Myoepithelioma of the retroperitoneum.
AB  - An abdominal mass detected in a 36-year-old man was thought from radiologic
      studies to be a renal neoplasm, but at surgery the kidney was found to be
      uninvolved. The 9.5-cm retroperitoneal tumor was resected totally and found to be
      encapsulated, and it appeared to be benign by light microscopy. The pattern of
      the spindle cells throughout the tumor suggested a cellular schwannoma, but
      immunocytochemical and ultrastructural studies did not support schwannian
      differentiation and instead revealed epithelial and smooth muscle features
      compatible with a myoepithelioma.

PMID- 7571083
TI  - Myofibroblastoma of the axilla.
AB  - A mass in the axilla of a 47-year-old woman was biopsied and resected. The mass
      was composed of a loosely distributed population of spindle cells that were
      immunoreactive for smooth-muscle actin. Ultrastructurally, the cells possessed
      abundant endoplasmic reticulum, and some contained peripheral smooth muscle
      myofilaments, establishing that they were myofibroblasts. Mitotic activity was
      sparse, there was no cytologic atypia, and by flow cytometry the tumor was
      diploid with a low S phase. A diagnosis of myofibroblastoma was favored, although
      the possibility of a low-grade sarcoma could not be excluded. There has not been
      any indication of recurrence over a 4-month period of follow-up.

PMID- 7571086
TI  - Dermatofibrosarcoma protuberans: ultrastructural and immunocytochemical
      observations.
AB  - In an attempt to elucidate the histogenesis of dermatofibrosarcoma protuberans,
      38 specimens were examined by electron microscopy and immunocytochemistry. The
      cumulative evidence strongly favors a fibroblastic/myofibroblastic derivation.

PMID- 7571088
TI  - Recurrent intrapulmonary malignant small cell tumor of the thoracopulmonary
      region with metastasis to the oral cavity: review of literature and case report.
AB  - Malignant small cell tumor of the thoracopulmonary region (MSCT) was first
      described in 1979 and has been referred to as the Askin tumor. This malignant
      neoplasm is a member of the peripheral primitive neuroectodermal tumor (PPNET)
      family and typically involves the periosteum, soft tissue, and extrapulmonary
      tissue of the thoracic wall. MSCT may also involve the lung parenchyma by local
      extension or may arise de novo in peripheral lung tissue. Local recurrence,
      abdominal involvement by tumor extravasation across the diaphragm, and skeletal
      metastatic disease are relatively common. However, metastasis to the head and
      neck region and in particular to the oral cavity is extremely rare. We present a
      recurrent intrapulmonary MSCT with metastasis to the oral cavity in an adolescent
      Hispanic boy, and review the literature regarding this member of the PPNET
      family. Differentiation from neuroblastoma may be made based on immunoreactivity
      for beta 2 microglobulin and HBA71 and lack of immunoreactivity for chromogranin
      in PPNET and MSCT. Ultrastructural features commonly seen in MSCT and PPNET are
      round to ovoid tumor cells with occasional cytoplasmic processes with relatively
      few pleomorphic dense core granules. These tumors lack the gangliocytic and
      Schwann cell differentiation that is characteristic of neuroblastoma. MSCT and
      PPNET have a common reciprocal cytogenetic translocation [t(11;22)q(24;q12)],
      which is shared with Ewing's sarcoma. Prognosis in MSCT is quite dismal, with a 2
      year survival of 38% and a 6-year survival of only 14%.

PMID- 7571087
TI  - Chordoid tumor: a light, electron microscopic, and immunohistochemical study.
AB  - Chordoid tumor--synonymous with chordoid sarcoma, parachordoma, and peripheral
      chordoma--is a very rare neoplasm with histologic similarity to chordoma that is
      found outside the axial skeleton. A soft tissue chordoid tumor in the gluteus
      maximus muscle of a 42-year-old man is presented. This tumor had morphologic
      features identical to a chordoma: nodular growth with vacuolated cytoplasm and
      myxomatous stroma by light microscopy, positive immunoreaction for cytokeratin
      and epithelial membrane antigen by immunohistochemistry, desmosomes,
      intercellular lumina lined with microvilli, and the presence of basal lamina
      material by electron microscopy. Two similar cases have been reported in the
      English literature.

PMID- 7571089
TI  - Neuroblastoma of the anterior mediastinum in an 80-year-old woman.
AB  - A 7-cm anterior mediastinal tumor in an 80-year-old woman was found by light and
      electron microscopy to be a neuroblastoma. Immunoreactivity for neuron-specific
      enolase, synaptophysin, and chromogranin supported the diagnosis. Neuroblastoma
      is an uncommon tumor in adults and we are not aware of a previous report of such
      a tumor in a patient of this age.

PMID- 7571091
TI  - Helicobacter pylori: I. Ultrastructural sequences of adherence, attachment, and
      penetration into the gastric mucosa.
AB  - New ultrastructural observations on the sequences of adherence, attachment, and
      penetration of Helicobacter pylori (HP) into the gastric epithelium were
      described in 32 endoscopic biopsies selected randomly from 168 samples of
      patients with active chronic gastritis. The adherence of HP to the target cell
      was initiated by direct contact with the microvillar coat, or glycocalyx, leading
      to the loss of that coat. The next step was demolishing of the surface
      microvilli, which separate the organisms from the cell cytoplasmic apices
      containing the main target of the HP, the mucoid granules. Thus the organisms
      come into close contact with the uncoated cell membrane and are ready for firm
      attachment. The attachment process was enhanced by the appearance of HP
      fibrillarlike strands (FLS). Up to three sites of attachment were recognized for
      individual organisms. Penetration into the apical cytoplasmic regions occurred by
      one of the organism's poles without damaging the host cell membrane. While a cell
      is being penetrated by one pole, FLS may extend from the other free pole to be in
      direct contact with the limiting membranes of the neighboring cell mucoid
      granules. Penetration into the gastric cells by a great number of organisms leads
      to serious cell damage and ultimately to cell disintegration. As a response, many
      neutrophils were found penetrating into the base of the gastric glands from the
      surrounding lamina propria; these cells were found damaged and disintegrated in
      the gland lumena. The neutrophils were absolutely HP-nonphagocytic. This study
      suggests that the dynamic activity of HP in the gastric epithelium and the
      possible release of the neutrophil granular contents in the gastric lumena play
      important roles in the gastric lesions during active chronic gastritis.

PMID- 7571090
TI  - Comparison of ultrastructural features among neuroblastic tumors: maturation from
      neuroblastoma to ganglioneuroma.
AB  - Neuroblastic tumors have the unique ability to differentiate and mature. This
      family of tumors is composed of the neuroblastoma, ganglioneuroblastoma, and
      ganglioneuroma. These tumors are derived from primordial neural crest cells that
      form the sympathetic nervous system. The purpose of this study was to
      characterize the ultrastructural features of neuroblastic tumors in a pediatric
      population. Forty-five neuroblastic tumors (15 neuroblastomas, 15
      ganglioneuroblastomas, and 15 ganglioneuromas) were examined using standard
      transmission electron microscopic techniques. Undifferentiated neuroblastomas
      were composed of primitive cells with rare neurite-like processes containing
      clear secretory vesicles and no Schwann cell differentiation. Poorly
      differentiated and differentiating neuroblastomas showed more frequent neuritic
      processes with infrequent dense core granules and infrequent immature Schwann
      like cells. Ganglioneuroblastomas possessed an admixture of cell types, including
      immature ganglion cells without associated satellite cells, intermediate cells,
      and differentiating neuroblasts. The neuropil contained immature Schwann cells
      encasing haphazardly arranged neuritic processes. Ganglioneuromas were composed
      of mature ganglion cells with occasional binucleation. The neuropil contained
      mature Schwann cells with well-organized neuritic processes and abundant collagen
      deposition. Differentiation or maturation of tumor cells, neuritic processes, and
      Schwann cells may thus be discerned ultrastructurally in primary neuroblastic
      tumors in pediatric patients.

PMID- 7571092
TI  - [Episiotomy--when?].

PMID- 7571093
TI  - [Changes in the use of episiotomy--methods and consequences].
AB  - The aim of the study was to evaluate the use of feedback by graphical profiles of
      rates of episiotomy and the impact on clinical practice and perineal state after
      spontaneous vaginal deliveries assisted by midwives with different attitudes
      towards episiotomy. We defined an observation period in our labour ward followed
      by feedback to the midwives concerning their own and the other midwives' use of
      episiotomies. The periods prior to and following the intervention were compared.
      All women (n = 3919) delivering during the two periods assisted by one of 30
      midwives with at least 20 deliveries during each period were included. The
      overall rate of episiotomy during the observation period was 37.1%. During the
      second period the rate was 6.6% lower (95% confidence interval (CI):3.6-9.6%)
      corresponding to a relative decrease of 17.8% (CI:10.1-24.7%). Higher rates of
      episiotomy during the observation period were associated with larger reductions
      in the second period. The decrease could be explained by the less frequent use of
      episiotomy in deliveries with rigid perineum or impending perineal tear. Compared
      with the observation period, 3.2% more women (CI:0.3-6.3%) had an intact perineum
      after delivery in the second period, and 3.4% more women (CI:0.4-6.2%)
      experienced perineal tears. The overall frequency of tears of the anal sphincter
      remained unchanged. However, women had slightly reduced frequency of tears of the
      anal sphincter if they were delivered by midwives who reduced a medium or high
      initial rate of episiotomy; and a tendency towards increased frequency of tears
      if they were assisted by midwives who reduced low initial rates (around 20%) of
      episiotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571094
TI  - [Ultrasonic angiography: principles and clinical use].
AB  - A new technique for detecting blood flow called Colour Doppler Energy (CDE),
      Power Doppler or Ultrasound Angio, is based on the integrated power spectrum of
      the standard Doppler signal used for Colour Flow Mapping (CFM). CDE is
      independent of the insonation angle, has no aliasing artefacts and improves the
      sensitivity with respect to detection of the presence or absence of flow compared
      to CFM. However, CDE provides no directional or quantitative information about
      the flow. CDE is superior to CFM in detection of low velocity flow, perfusion in
      small vessels, flow in torsioned vessels and flow in multiple vessels in the same
      image plane. The clinical applications are reviewed. Complicated stenosis, renal
      perfusion, penile Doppler and scanning of the vessels of the extremities are
      examples where CDE improves sensitivity in detecting flow compared to CFM.

PMID- 7571096
TI  - [Registration in medical journals of prescriptions for strong analgesics
      prescribed by general practitioners].
AB  - The use of strong analgesics was continuously registered in 90 patients
      throughout 12 months via the public health authorities, who are responsible for
      the control of prescription of strong analgesics. After the 12 months,
      questionnaires were sent to the prescribing doctors about the treatment during
      that period. Twenty-five patients were excluded mainly due to incomplete data and
      non-responding GPs. Analysis of validity of the GPs' registration, with the
      public health authorities' registration used as the reference standard, showed
      90% (95% confidence limits (CL):68-99%) agreement concerning continuing treatment
      with strong analgesics and 98% (CL:88-100%) regarding GPs' registration of
      patients not being treated with strong analgesics. In all, misclassification
      occurred in 5% (CL:1-13%) of the patients. Our study suggests that the GPs'
      information about prescriptions of strong analgesics is valid, and that it can be
      used in research.

PMID- 7571095
TI  - [Necrotizing pancreatitis].
AB  - Acute pancreatitis is in the majority of patients a mild, self-limiting illness.
      Five to fifteen percent of the patients develop acute necrotizing pancreatitis, a
      severe illness with a high morbidity and mortality. Secondary infection of the
      pancreatic necrosis (infected pancreatic necrosis) is the main cause of death.
      Pancreatic necrosis is identified with a high accuracy by contrast-enhanced
      computed tomography. The differentiation between sterile and infected necrosis
      requires demonstration of bacteria or fungi isolated from the necrosis. Surgical
      treatment of a sterile necrosis remains controversial, but there is a tendency
      towards conservative non-operative treatment. Infected pancreatic necrosis is
      regarded as an absolute indication for surgery, untreated the mortality is
      approximately 100%. The aim of modern treatment is to remove the pancreatic
      necrosis continuously. This has successfully been done by the open packing
      method, with or without subsequent drainage. At present no randomized trials
      comparing the different treatment modalities are available. The question of
      prophylactic antibiotics still remains unanswered. For the present imipenem 0,5 g
      x 3 is recommended.

PMID- 7571097
TI  - [Heart surgery in private practice].
AB  - During the period May 1993-August 1994, 100 patients were operated upon with
      heart surgery at the Private Hospital Hamlet (Copenhagen). Preoperative risk
      factors such as age > 70 years, female gender, ejection fraction (EF) < 40%,
      diabetes mellitus, adipositas > 20% above normal weight, were associatet with an
      increased mortality rate among those cases (5.4%). Overall mortality was 4%. The
      results are fully comparable with international reports.

PMID- 7571099
TI  - [Solid papillary tumor of the pancreas].
AB  - Solid papillary tumours of the pancreas are rare. The tumours are large and show
      a predilection for young women. There have been few reports of metastasizing
      tumours, but generally the prognosis is good after surgical removal. Three case
      histories are reported here.

PMID- 7571098
TI  - [Pancreaticoduodenectomy (Whipple's operation) for periampullary cancer].
AB  - This study evaluated the indications for and effects of pancreaticoduodenectomy
      (102 patients) or total pancreatectomy (15 patients) with extensive lymph node
      dissection performed upon 117 patients with periampullary adenocarcinoma.
      Presenting symptoms and postoperative morbidity and mortality rates were
      recorded. Cumulative survival rates were evaluated in relation to origin, size,
      and staging of tumour. The postoperative mortality rate after Whipple's operation
      was 8% (eight patients). The median survival period was 1.1 year and the overall
      five year survival rate was 15% (confidence limits, 5 to 25%). The five year
      survival rate for patients without tumour extension beyond the pancreas was 25%
      (confidence limits, 5 to 50%), and in patients with adenocarcinoma of the ampulla
      af Vater, 34% (confidence limits, 3 to 65%). The median survival rate in patients
      with adenocarcinoma of the ampulla of Vater was 3.3 years, which was
      significantly longer than in the other patients. Fifty-nine patients with distant
      spread could be divided into 14 patients with para-aortic lymph node metastases
      who had a significantly shorter survival period than 45 patients without para
      aortic lymph node metastases (p = 0.004). Resection of periampullary carcinoma
      provides a better palliation and survival rate than nonoperative biliary drainage
      or bypass operation. An improved preoperative verification of para-aortic
      metastases could restrict resection to patients with a prognostic five year
      survival rate of more than 25% and a postoperative mortality rate of less than
      5%.

PMID- 7571100
TI  - [Chronic pancreatitis and upper gastrointestinal hemorrhage].
AB  - A 46 year-old woman with a history of chronic pancreatitis, upper epigastric pain
      and upper gastrointestinal bleeding of obscure origin is presented. A haemoductal
      pancreatitis was the source of bleeding due to erosion of the splenic artery with
      bleeding into a pancreatic pseudocyst communicating with the pancreatic duct.
      This case was special, because there was no aneurysmal dilatation of the splenic
      artery. This rare entity must always be considered in the diagnosis of
      gastrointestinal haemorrhage of obscure origin. The appropriate investigation to
      confirm the diagnosis is visceral angiography, if necessary followed by CT-scan
      of the abdomen.

PMID- 7571101
TI  - [Denmark has satisfactory blood transfusion service].

PMID- 7571102
TI  - [Hepatitis B and occupational risk groups].

PMID- 7571103
TI  - [Future drug utilization].

PMID- 7571104
TI  - [Acute viral hepatitis--a constant threat].

PMID- 7571105
TI  - [Hepatitis epidemic among drug addicts in Esbjerg from July 1993 to May 1994].
AB  - During 11 months from July 1993 to May 1994 the Department of Internal Medicine
      at Esbjerg Centralsygehus saw 19 patients with acute hepatitis A, B and/or C. In
      a normal year one to three patients are admitted with acute viral hepatitis.
      Sixteen of the patients reported intravenous drug use, half of them only
      sporadically, i.e. once or twice a month. Acute hepatitis A, B and C were seen in
      seven different combinations, the most frequent being acute hepatitis B in a
      hepatitis C antibody positive patient. The occurrence of acute hepatitis A in
      this group of patients may be due to parenteral transmission. Among 10 patients
      tested for HIV antibodies, none were found to be positive. In Esbjerg, which is
      the fifth largest city in Denmark, an automat with clean needles and syringes was
      installed six months after the culmination of the epidemic.

PMID- 7571106
TI  - [Molecular biology and prenatal diagnosis].

PMID- 7571108
TI  - [Changes in neonatal mortality and morbidity of very low birth infants in the
      county of Nordjylland].
AB  - The purpose of the study was to investigate changes in neonatal mortality and
      morbidity in infants with very low birthweight born in the county of northern
      Jutland, Denmark. The study was retrospective and included infants with
      birthweight < or = 1500 grams born in northern Jutland. The period 1988-1989 was
      compared to the period 1990-1993. Two hundred and seventy (270) infants were
      included. A decrease in neonatal mortality from 27% to 18% was found, and for
      infants with birthweight < or = 1000 grams the neonatal mortality declined from
      60% to 28%. Possible explanations were a higher frequency of betamethasone
      administration and the introduction of surfactant into routine medical care. The
      median birthweight declined by just under 100 grams. The frequency of clinically
      significant periventricular haemorrhage and the frequency of bronchopulmonary
      dysplasia did not increase. Long-term follow-up is necessary for the evaluation
      of the final results of the increased neonatal survival.

PMID- 7571107
TI  - [Neonatal mortality, morbidity and late sequelae in infants with birth weight
      under 1.501 gr or gestational age under 31 weeks, primarily admitted to a central
      hospital].
AB  - The purpose of the study was during a three year period from 1990 to 1992 to
      describe the neonatal mortality, morbidity and the late complications of 75 very
      low birth weight infants primarily treated in the neonatal department of a County
      Hospital. The study was performed retrospectively. The mean birth weight was 1292
      g in (range 755-2046 g) and the mean gestational age 29.9 weeks (range 25-37
      weeks). The primary choice of treatment was nasal continuous positive airway
      pressure (nasal-CPAP) and "minimal handling" regime. When needed surfactant
      administration and/or mechanical ventilation was used. Twenty neonates (27%)
      received mechanical ventilation, and 14 (19%) were treated with surfactant
      (Curosurf). The mortality (8%) (95% confidence limits 2.9%-16.6%) and morbidity
      is low. Late complications such as cerebral palsy or mental retardation were seen
      in eight infants (12.1%) (95% confidence limits 5.4-22.5%). The results of our
      treatment seem acceptable, and confirm an increasing survival among very low
      birth weight infants.

PMID- 7571109
TI  - [Primary intracranial and intraspinal neoplasms in Denmark 1943-1987].
AB  - This is a descriptive study of primary intracranial and intraspinal tumours
      notified to the national Danish Cancer Registry during the years 1943-1987. A
      total of 19,317 cases of benign and malignant neoplasms were included over these
      45 years with a doubling of the age-standardized incidence rates for both men and
      women from start till end of the registration period. The trend was mainly
      explained by markedly increasing rates in the age groups 60 years or above at
      diagnosis. Approximately some 74% of tumours were derived from the brain tissues
      and 19% from the intracranial and intraspinal meninges. Meningiomas predominate
      among women with a male:female ratio of 0.5, while tumours of the brain tissues
      predominate among men (ratio 1.3). Meningiomas are more frequently encountered as
      a chance finding at autopsy compared to other types of intracranial and
      intraspinal tumours. The above-mentioned increase in age-specific incidence is
      due mainly to improved diagnostic capabilities over the period and a subsequent
      decrease in the underreporting of these tumour types.

PMID- 7571110
TI  - [Non-surgical treatment of bleeding gastric ulcer. A follow-up after 5-8 years].
AB  - Gastric ulcer haemorrhage is associated with a high immediate mortality, but few
      data exist on the late prognosis of these patients. The aim of this study was to
      determine the long-term recurrence rate and late outcome in patients with gastric
      ulcer complicated by bleeding. In a prospective follow-up study 90 consecutive
      patients with a bleeding gastric ulcer discharged after non-operative treatment
      (bleeding controlled by endoscopic electrocoagulation or ceased spontaneously)
      were followed up once every year for five to eight years (median 6.5 years).
      Recurrent ulcer was seen in 17 patients, repeat haemorrhage being the presenting
      symptom in 13. The estimated cumulative recurrence rate after two, five and eight
      years was 10%, 19% and 33%, respectively. Recurrence rate was unaffected by sex,
      complicating disease, and NSAID ingestion before and after the index bleeding
      episode. The recurrence rate of patients with a history of ulcer before the index
      bleeding episode did not differ from that of patients with no previous ulcer
      history. A significantly increased risk of recurrence was seen in patients with
      previous bleed as opposed to patients with previous non-bleeding ulcer (p <
      0.05). The cumulative survival rate was significantly reduced compared to the
      expected survival rate of the sex- and age-matched background population (p <
      0.01), primarily due to diseases not related to the ulcer disease. CONCLUSION:
      Bleeding gastric ulcer is associated with a relatively low long-term recurrence
      rate, except in a few patients with a history of previous bleeding ulcer, who
      have an increased risk of recurrence. Patients with bleeding gastric ulcer have
      an excess mortality not related to the ulcer disease.

PMID- 7571111
TI  - [False results on elevated triiodothyronine values in radioimmunoassay].
AB  - Five patients with falsely elevated serum triiodothyronine (T3) concentrations (>
      9 nmol/l) in a radioimmunoassay are reported. The high T3-values disagreed with
      the other thyroid variables investigated as well as with the clinical
      observations. In sera from all patients a normal non-specific binding of T3 was
      found, thus excluding abnormal serum-protein-binding of the hormone. An ethanol
      extraction of T3 from serum before RIA reduced the T3 content in serum from all
      patients to normal levels (2.0-2.4 nmol/l). These findings indicate the presence
      in the sera of substances, probably of protein nature, that were interfering with
      the assay by binding the reagent-antibody and not the antigen. Addition of non
      immune rabbit serum prevented this interference and normalized the T3-values (1.8
      2.4 nmol/l). Thus the interfering substance in T3-RIA could be an anti-rabbit
      antibody, the interaction of which can be eliminated by a minor modification of
      the assay making it possible to differentiate true from false T3-values.

PMID- 7571112
TI  - [Problems in thyroid function screening using thyroid stimulating hormone. A case
      of thyrotoxicosis caused by a thyroid stimulating hormone-secreting pituitary
      tumor].
AB  - In a new consensus report from the Danish Society of Internal Medicine a
      sensitive TSH assay is recommended for screening for thyroid diseases. A patient
      with thyrotoxicosis, normal serum TSH and a TSH-secreting pituitary adenoma is
      described. Other reasons for discrepancies between thyroid clinical status and
      serum TSH are mentioned: Target organ resistance to thyroid hormone, interference
      in the radioimmunoassay with heterophilic antibodies and insufficient production
      of TSH because of pituitary disease. IN CONCLUSION: Screening with TSH is
      acceptable, but if any discrepancy between TSH values and the clinical picture is
      found, further tests must be made.

PMID- 7571113
TI  - [Rapidly progressing glomerulonephritis. Microangiitis associated with antibodies
      against the glomerula membrane].
AB  - A 53 year old man first presented with a mild anti-neutrophil cytoplasmic
      antibody (ANCA), type (MPO-ANCA) associated microscopic polyangiitis.
      Approximately one year later, he presented with fatigue, fever, cough, sore
      muscles and erythrocyturia. At admission he was uraemic. Kidney biopsy showed in
      LM extracapillary glomerulonephritis and in immunofluorescence microscopy linear
      deposition of IgG along the glomerular basement membrane (GBM). MPO-ANCA was
      still positive, but antibodies against GBM were now also present. Retrospective
      analysis revealed the presence of anti-GBM antibodies nine months before clinical
      illness. Pr3-ANCA (C-ANCA) was negative during the whole course. In spite of
      decreasing anti-GBM antibody levels during treatment, his condition aggravated,
      and he died from complications. Thus, coexisting anti-GBM antibodies may explain
      suddenly deteriorating renal function in patients with ANCA associated
      vasculitis.

PMID- 7571114
TI  - [Treatment of hypertension with calcium antagonists and increased risk of acute
      myocardial infarction: reliable results?].

PMID- 7571115
TI  - [Opioids and receptor blocking].

PMID- 7571116
TI  - [Registration of fever of unknown origin].

PMID- 7571117
TI  - PHOELIX: a package for semi-automated helical reconstruction.
AB  - We describe a set of procedures and algorithms which have been developed to
      provide an efficient and reliable method for reconstructing a three-dimensional
      density map from specimens with helical symmetry. These procedures build on the
      original MRC helical processing suite, with extensions principally developed
      using the SUPRIM image processing package. Actomyosin is used as a model specimen
      to demonstrate the utility of this repackaged and expanded set of routines. The
      time required to complete a three-dimensional map has been reduced from several
      weeks using traditional manual techniques to a few days. The increased
      signal/noise provided has allowed for the extraction of additional layer lines
      not previously identified by manual techniques.

PMID- 7571118
TI  - Automatic particle picking from electron micrographs.
AB  - A computer program for automatic particle picking based on textural methods is
      proposed. The technique relies on the evaluation of certain textural parameters
      for data windows containing single particles, and those containing undesirable
      material. These parameters are manipulated by a discriminant analysis routine for
      determining the rules of classification between the different categories. The
      effectiveness of the method was demonstrated by application to electron
      micrographs of 70S Escherichia coli ribosomes.

PMID- 7571119
TI  - A marker-free alignment method for electron tomography.
AB  - In electron tomography of biological specimens, fiducial markers are normally
      used to achieve accurate alignment of the input projections. We address the
      problem of alignment of projections from objects that are freely supported and do
      not permit the use of markers. To this end we present a new alignment algorithm
      for single-axis tilt geometry based on the principle of Fourier-space common
      lines. An iterative scheme has been developed to overcome the noise-sensitivity
      of the common-line method. This algorithm was used to align a data set that was
      not amenable to alignment with fiducial markers.

PMID- 7571120
TI  - An imaging filter for biological applications.
AB  - A recently developed post-column imaging filter optimized for biological electron
      microscopy is described. The filter uses a single magnetic prism, four strong
      quadrupole lenses and five sextupole lenses to form images and spectra free of
      all important aberrations and distortions of first and second order. The
      performance of the filter is illustrated with practical applications. It is shown
      that the filter offers several important advantages over currently existing in
      column filters, particularly in the areas of imaging at low magnifications,
      attainable collection efficiency, energy resolution, and general spectroscopic
      operation.

PMID- 7571122
TI  - Scapula length measurement for assessment of fetal growth and development.
AB  - To determine the value of prenatal ultrasonographic scapula measurements for
      fetal growth and development as an adjunct to assessing in utero development, a
      prospective study of ultrasonography was conducted in 343 pregnant women with
      uneventful pregnancies with gestational ages from 16 to 41 weeks, and several
      biometric measurements were obtained. The relationships of scapula length with
      gestational age and with biparietal diameter, femur length, abdominal
      circumference and scapula length were examined. With the ultrasonographic
      examinations of 343 healthy pregnant women, a nomogram of scapula length
      measurements estimating gestational age and predicting the biparietal diameter,
      abdominal circumference, and femur length was generated. Linear relationships
      were found between the scapula length  and the gestational age (R2 = 0.94, p <
      0.0001), the biparietal diameter (R2 = 0.94, p < 0.0001), abdominal circumference
      (R2 = 0.94, p < 0.0001), and the femur length (R2 = 0.95, p < 0.0001). The rate
      of increase of scapula length was significantly higher before 28 weeks of
      gestation than in later pregnancy (p < 0.0001). The correlation coefficients
      between gestational age and scapula length were 0.95 before 28 weeks of gestation
      and 0.86 in later weeks. These results suggest that scapula length measurement is
      a valuable parameter for the assessment of fetal growth and development.

PMID- 7571123
TI  - Maturation of the testis: ultrasound evaluation.
AB  - We performed a prospective study to investigate whether the sonographic
      appearance of the testicular parenchyma changes during maturation of the testis.
      One hundred forty-three boys ranging in age from 6 months to 16 years, and 11
      volunteers aged about 30 years, were included in the study. The echogenicity of
      each of the 308 normal testes were determined by measuring the average brightness
      of a histogram over a defined testicular area. To avoid divergent results due to
      different settings of the device in individual cases, the average brightness of a
      histogram of a standard ultrasound phantom was measured immediately after the
      examination of each testicle. From these 2 measurements, testicular echogenicity
      could be calculated independently of individual equipment settings. All testes
      had a homogeneous echotexture. The echogenicity of the prepubertal testis was
      markedly reduced compared to the medium-level echogenicity of the mature testis
      (p < 0.001). Testicular echogenicity increases during puberty. We conclude that
      testicular echogenicity increases with maturation. Knowledge of this fact may
      improve the diagnostic performance of scrotal ultrasound especially in children.

PMID- 7571121
TI  - Cryo-electron energy loss spectroscopy: observations on vitrified hydrated
      specimens and radiation damage.
AB  - Valence electron energy loss spectroscopy (EELS) has been used to characterize
      the composition of frozen-hydrated specimens in the electron microscope. Fine
      structure in the energy range up to 30 eV provides a means of distinguishing
      between vitreous and crystalline ice. Some features of the ice spectrum can be
      understood in terms of transitions between molecular orbitals in the water
      molecule and by the existence of excitons in the solid. Spectra from hydrated
      biological specimens can be analyzed to obtain quantitative estimates of the
      water content by fitting contributions from the ice and organic components. EELS
      also provides information about the radiation chemistry that occurs when hydrated
      specimens are exposed to the electron beam. From the observation of the hydrogen
      K-edge at approximately 13 eV, it can be deduced that bubbles of molecular
      hydrogen are evolved during irradiation at doses of > 10(4) nm-2, and that these
      bubbles contain gas at pressures in excess of one thousand atmospheres.

PMID- 7571124
TI  - Discrimination of intravascular lumen and dissections in single intravascular
      ultrasound images using subtraction, conventional averaging and saline flush.
AB  - With current 30-MHz intravascular ultrasound systems, flowing blood may cause
      considerable backscatter which in real-time images is characterized by dynamic
      speckle. However, in a single intravascular ultrasound image (still-frame) the
      discrimination between arterial lumen and wall may be difficult due to the frozen
      intraluminal speckle, particularly in the presence of dissections. We compared
      subtraction, averaging and saline flush as methods to improve the discrimination
      between arterial lumen and wall in a single image. The real-time images served as
      gold standard. In 22 patients who underwent peripheral balloon angioplasty,
      ultrasound images obtained from 84 sites were examined. The sensitivity and
      specificity of detecting dissections were in the subtraction image 85% and 100%,
      in the averaged image 57% and 96%, and in the saline flush image 58% and 86%,
      respectively. Subtraction is a promising method to outline the irregular lumen in
      a single image.

PMID- 7571125
TI  - Effectiveness of galactose-based intravenous contrast medium on color Doppler
      sonography of deeply located hepatocellular carcinoma.
AB  - The purpose of this study is to examine the effectiveness of intravenously
      injectable sonographic contrast medium for color Doppler sonographic diagnosis of
      deeply located hepatocellular carcinoma. Subjects were 7 hepatocellular
      carcinomas, an adenomatous hyperplasia and a hemangioma located more than 7 cm
      below the abdominal surface. Levovist, a galactose-based sonographic contrast
      medium was injected through median cubital vein as a phase-two clinical study,
      and the pre- and post-enhanced color Doppler sonographic findings of these
      lesions were compared. The incidence of the positive findings for hepatocellular
      carcinoma increased from 29% (2/7) to 86% (6/7) of hepatocellular carcinoma after
      contrast enhancement. Positive findings were 0% in other cases even after
      enhancement. Levovist brought a certain improvement in the visualization of the
      tumor vessel by color Doppler sonography without any noteworthy side effects.
      Contrast enhancement was useful for the diagnosis of liver lesions suspected to
      be hepatocellular carcinoma by ordinary sonography, but could not be confirmed by
      color Doppler sonography.

PMID- 7571126
TI  - Characterization of ultrasonic B-scans using non-Rayleigh statistics.
AB  - The envelope of the ultrasonic echo backscattered from tissues is modeled using
      non-Rayleigh statistics, namely the K-distribution. We show that the K
      distribution can be used to describe the envelope of the echo, and its parameters
      may be used to distinguish between different regions in ultrasonic B-scan images.
      The validity of the model is tested using phantoms. Preliminary results indicate
      that the parameters of the K-distribution may be used to separate targets, in
      which the number of scatterers or the scattering cross-sections differ from that
      of the background. The method of employing the parameters of the K-distribution
      appears to be better than the methods based solely on the signal-to-noise ratio.

PMID- 7571127
TI  - A noninvasive method to estimate wall shear rate using ultrasound.
AB  - Wall shear stress (blood viscosity x wall shear rate), imposed by the flowing
      blood, and blood pressure are the main mechanical forces acting on a blood vessel
      wall. Accurate measurement of wall shear stress is important when investigating
      the development of vascular disease, since both high and low wall shear stresses
      have been cited as factors leading to vessel wall anomalies. Furthermore, in
      vitro studies have shown that endothelial cells, which play a key role in the
      function of the underlying arterial wall, undergo a variety of structural and
      functional changes in response to imposed shear stress. However, there is
      practically no knowledge about the influence of wall shear stress on the arterial
      wall in vivo because of the difficulty in measuring this stress in terms of
      magnitude and time variation. The method presented in this article to measure the
      time-dependent wall shear rate in the main arteries is based on the evaluation of
      velocity profiles determined by means of ultrasound, using off-line signal
      processing. Pulsed ultrasound is well suited for this application since it is
      noninvasive. The processing performed in the radio-frequency (RF) domain consists
      of a mean frequency estimator preceded by an adaptive vessel wall filter. In a
      pilot study (30 measurements in the carotid artery of five healthy volunteers) we
      investigated the reproducibility of our method to estimate wall shear rate as
      compared with the reproducibility of the measurement of blood flow velocity in
      the middle of the vessel. The coefficient of variation was on the order of 9% for
      blood flow velocity estimation, and for wall shear rate estimation on the order
      of 5%.

PMID- 7571128
TI  - The effect of refraction and assumed speeds of sound in tissue and blood on
      Doppler ultrasound blood velocity measurements.
AB  - The combined effect of three assumptions relating to refraction, the speed of
      sound in tissue and the speed of sound in blood on the accuracy of Doppler
      ultrasound blood velocity measurements has been investigated. A theoretical
      relationship giving the net velocity measurement error introduced by these three
      assumptions has derived using a model in which tissue and blood layers are
      separated by straight, parallel boundaries. This net error is dependent on the
      assumed and actual speed of sound in tissue, the assumed speed of sound in blood
      and the Doppler angle, but is effectively independent of the actual speed of
      sound in blood. For clinical blood velocity measurements, the net error is
      estimated to be as much as an 8% overestimation of the actual velocity, higher
      than previously predicted for any of the factors individually. The relationship
      also predicts a net velocity measurement error in experimental flow systems and
      string phantoms which is dependent on the speed of sound in the liquid bath. A
      water bath at room temperature will give an overestimation of approximately 2%.
      Experimental investigations using conventional and modified string phantoms and a
      5-MHz linear phased array system support these conclusions. The effect of
      perturbing the layers from their parallel orientation has also been considered
      theoretically and has provided additional support for the above conclusions.
      These results may help more accurate Doppler velocity measurements in both
      experimental and clinical settings.

PMID- 7571130
TI  - Feasibility study for a two-dimensional diagnostic ultrasound velocity mapping
      system.
AB  - A receive beam-tracking technique is introduced for simultaneously measuring more
      than one dimension of an existing velocity vector in medical ultrasound. By using
      flexible beamforming and a conventional linear-array transducer, vectors can be
      measured at real-time frame rates over a significant field of view. Both
      simulations and in vitro experiments show that this technique should provide more
      accurate measurements of blood flow velocities in the human body than is
      available with current color flow mapping systems.

PMID- 7571129
TI  - Volumetric blood flow calculation using a narrow ultrasound beam.
AB  - Spectral analysis of the Doppler signal from a negligibly thin ultrasound beam
      directed through the centre of the blood vessel can, for certain forms of
      velocity profile, produce a statistic deemed to be proportional to spatial mean
      blood velocity. A statistic recently derived for the case of an axisymmetric,
      monotonic velocity profile is generalised to the situation where the profile is
      axisymmetric and made up of a central monotonic section inside a region of
      reverse flow which is itself symmetric. Using the theory of oscillating flow in a
      rigid tube, instantaneous velocity profiles were derived for samples of actual
      cardiac cycles recorded from various arterial sites. In every case the profiles
      satisfied the assumptions for the statistic to be valid throughout considerable
      regions of each cycle. The resulting error in the use of the statistic to measure
      the volumetric flow in a cycle had a magnitude less than 0.01% for the carotid,
      radial and brachial artery recordings, was typically small and positive (+2.5%)
      for the common femoral artery, and was typically negative (0 to -8%) for the
      superficial femoral artery, with outlying value of -16%.

PMID- 7571131
TI  - When can Doppler be used in place of integrated backscatter as a measure of
      scattered ultrasound intensity?
AB  - The purpose of this work was to determine under what circumstances the intensity
      of Doppler audio signals can be used as a substitute for the more direct and
      complex measure of ultrasonic backscatter (integrated backscatter) which requires
      radio-frequency ultrasound signals. Using a rotating rubber disk phantom and a
      microbubble echo-contrast flow phantom, we have shown that the intensity of audio
      Doppler signals is independent of the constraints typically associated with
      Doppler ultrasound (velocity and angle), but like integrated backscatter depends
      on the transmit intensity, gain of the ultrasound receiver, attenuation and the
      nature of the scatterers. Using Doppler ultrasound for backscatter measurements
      is ideally suited for the expected application of the technique: the assessment
      of echo contrast in cardiac chambers, blood vessels and tissue perfusion (i.e.,
      any flow system). Compared to integrated backscatter, the Doppler audio method
      has the advantage of using standard clinical ultrasound machines, requires less
      sophisticated data storage and processing equipment and the positioning system
      for the region of interest (the Doppler sample volume) is built into all pulsed
      wave Doppler machines. Further, the low-velocity filter removes all nonmoving
      scatterers (like the intense echoes from heart valves and the walls of blood
      vessels), thus allowing study of only those echoes originating from the blood
      pool. This combination of features is what attracted us to the Doppler method for
      quantitating ultrasonic backscatter in flow systems.

PMID- 7571132
TI  - The effects of successive high-energy shock-wave tumor administration on tumor
      blood flow.
AB  - The effects of repeated high-energy shock wave (HESW) tumor administration on
      tumor blood flow (TBF) were studied in NU-1 human kidney cancer xenografts.
      Deuteriated water was used as a magnetic resonance spectroscopic detectable
      tracer for measuring tumor blood flow. Tumors were exposed twice to 800
      electromagnetically generated HESW, with a 24-h interval or sham exposed. No
      changes in TBF occurred after sham exposure to HESW. TBF levels 2 h after the
      first and second HESW application were, respectively, 46% and 37% lower than the
      mean preexposure TBF value and returned to normal levels within 16 h. There was
      statistically no difference found between the effects on tumor blood flow after
      the first and second HESW exposure. These observations are in agreement with
      earlier studies and provide a rationale to shorten the time interval between HESW
      monotreatments to 2 to 3 h.

PMID- 7571133
TI  - Thresholds for hemorrhages in mouse skin and intestine induced by lithotripter
      shock waves.
AB  - In vivo biological effects of ultrasound should be characterized as thermal or
      cavitational to understand their etiology and significance. A spark-gap shock
      wave lithotripter was built and used to compare cavitation-induced hemorrhages to
      the heat-induced petechial hemorrhages caused by continuous-wave ultrasound in
      mouse intestine. Intestinal hemorrhages induced in anesthetized hairless mice by
      the lithotripter pulses involved tissue destruction with bleeding into the lumen
      of the intestine, and were associated with intestinal gas bubbles. Skin
      hemorrhages were also observed, which appeared to be contusions, with no actual
      breakage of the skin. Administration of 100 shock waves with peak positive
      amplitude of 18.5 MPa produced an average of 7.6 (standard error [SE] 3.1, n = 6)
      intestinal hemorrhages and 45 (SE 11) skin hemorrhages. The counts and severity
      of hemorrhages increased with increasing numbers (3 to 300) of shock waves.
      Absorbers of varying thickness were used to reduce the pressure amplitude of the
      shock waves, which were thereby modified into low frequency ultrasound pulses.
      For 100 pulse exposures, apparent thresholds for effects occurred between 1.6 and
      4.0 MPa for the intestinal hemorrhages and between 0.6 and 1.6 MPa for the skin
      hemorrhages. The low 1-Hz pulse repetition frequency precluded significant
      heating, and so these effects were the result of cavitation, which probably
      occurred inside the intestines or in the surrounding water. Compared to the
      previously observed thermal petechia, the cavitation-induced hemorrhages could be
      distinguished on the basis of their appearance upon histological examination, and
      also by the relative values of the thermal and mechanical exposure indices
      associated with the two different exposure modes.

PMID- 7571134
TI  - The performance of different pressure pulse generators for extracorporeal
      lithotripsy: a comparison based on commercial lithotripters for kidney stones.
AB  - By using needle hydrophones and a PC-controlled experimental set-up, the acoustic
      output of 10 commercial extracorporeal shock-wave lithotripters has been
      measured. The pressure field was measured in the focus, along the beam axis, in
      the focal plane and "at the skin level" (a plane orthogonal to the beam axis, 5
      cm backward from the focus, assumed as the entrance site of the pressure pulse
      into the patient's body). The set of tested instruments included the three
      technologies nowadays in use to generate the pressure pulse, namely
      electrohydraulic, electromagnetic and piezoelectric. Notwithstanding large
      intratechnology variability, the results indicate that electrohydraulic and
      electromagnetic generators can provide comparable performances. Piezoelectric
      generators produced pressure pulses with less energy than the others. Possible
      implications of the experimental results on treatment safety and effectiveness of
      kidney stone destruction are discussed.

PMID- 7571135
TI  - Acoustic properties of some biocompatible polymers at body temperature.
AB  - In response to the many invasive applications of ultrasound which are developing,
      the acoustic properties of several aliphatic and aromatic polyurethanes and
      Polyether block amide (PEBA) copolymers are presented. These polymers were
      reported by their manufacturers as being biocompatible and are possibly suitable
      for short-term implantation in humans. Speed and attenuation of sound are
      measured at 37 degrees C as a function of frequency by use of a Fourier-transform
      method. These properties are reported in tabular and graphic form.

PMID- 7571137
TI  - Umbilical cord venous pulsation in normal fetuses and its incidence after 13
      weeks of gestation.
AB  - A total of 1175 umbilical venous Doppler flow velocity waveforms were acquired
      from 449 normal pregnant women whose fetuses were delivered at term without
      neonatal asphyxia or anomalies. Arterial and venous flow velocity waveforms were
      acquired from a free loop of the umbilical cord. The incidence of umbilical
      venous pulsation decreased from 30.4% at 13-14 weeks of gestation to 14.8% at 21
      22 weeks of gestation. After 23 weeks, this incidence was settled within 5.0
      7.8%. There was no difference between the umbilical arterial resistance index of
      the fetuses with venous pulsation and without pulsation before 22 weeks. But the
      resistance index was lower in the pulsatile fetuses than in the nonpulsatile
      fetuses after 23 weeks of gestation. The origin of venous pulsations before early
      second trimester was suspected to be different from that after late second
      trimester.

PMID- 7571136
TI  - Serial assessment of adnexal masses with transvaginal color Doppler sonography.
AB  - Transvaginal color Doppler sonography (TV-CDS) was performed on 64 women with
      adnexal masses at 3, 6 and 12 weeks after initial presentation. In 47 (72% of
      patients studied), the pelvic mass demonstrated a decrease in size and increase
      in pulsatility index (PI) after 12 weeks. Of the patients undergoing surgery in
      this group, one had a tubo-ovarian abscess, one diverticular abscess and one
      hydrosalpinx. In seven patients (10%), there was no change in size or PI. Three
      in this group had an endometrioma, whereas two had a peritoneal cyst. In five
      (7%), there was no change in size and an increase in PI. One of these patients
      had a mucinous cystadenoma. In three (5%), there was a decrease in size and PI.
      Two of these patients had a tubo-ovarian abscess. In two (3%) patients studied,
      the mass showed an increase in size and decrease in PI; both had corpora luteum
      cysts with acute hemorrhage. Seventy-two percent of masses with high impedance
      underwent regression, whereas only 21% of lesions with low impedance did. Only
      20% of masses demonstrating low impedance or morphologically complex structure
      regressed. Sixty-five percent of lesions that regressed had a significant drop in
      PI, whereas all the lesions that showed no change in size or enlargement had
      either no change or decrease in PI. Probability of regression was the greatest in
      young women (less than 40 years of age) and in masses < 5 cm. Ninety-three
      percent of women with persistent masses that underwent progestational suppression
      demonstrated regression with decrease of PI and peak systolic velocity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571138
TI  - Doppler ultrasound spectral shape downstream of significant arterial stenosis in
      vivo.
AB  - Peak analysis was applied to pulsed Doppler ultrasound spectra from in vivo
      poststenotic velocity fields of canine common carotid arteries. Turbulent spectra
      from a region of jet breakup, five diameters (5 D) down from a 68% diameter
      reducing stenosis, were closely approximated by a single Gaussian peak. Multiple
      peaks resulting from the analysis of complex spectra from the shear layers
      between jet and recirculation zones, 1.5 D downstream of a 40% stenosis,
      correlated well with the known features of the poststenotic velocity field. It is
      concluded that peak analysis can be used to separate the spectral components of
      distinct flow regimes from the complex spectra of regions of complicated flow.
      This may provide a method for the diagnosis of mild degrees of arterial stenosis
      using pulsed Doppler ultrasound.

PMID- 7571139
TI  - Atrial inflow can alter regurgitant jet size: in vitro studies.
AB  - Recent studies have attempted to predict the severity of regurgitant lesions from
      color Doppler jet size, which is a function of orifice momentum for free jets.
      Jets of mitral and tricuspid regurgitation, however, are opposed by flows
      entering the atria. Despite their low velocities, these counterflows may have
      considerable momentum that can limit jet penetration. The purpose of this study
      was to address the hypothesis that such counterflow fields influence regurgitant
      jet size. Steady flow was driven through 2.4- and 5.1-mm-diameter circular
      orifices at 2 to 6 m/s. At a constant orifice velocity and flow rate, the
      velocity of a uniform counterflow field was varied from 5 to 30 cm/s. Jet
      dimensions were measured by both fluorescent dye visualization and Doppler color
      flow mapping. The results showed that despite its relatively low velocities,
      counterflow dramatically curtailed jet length and area. Jet dimensions were
      functions of the ratio of jet to counterflow momentum. Thus, atrial inflow may
      participate in determining jet size and can alter the relation between jet size
      and lesion severity in mitral and tricuspid regurgitation.

PMID- 7571140
TI  - Doppler velocity ratio measurements evaluated in a phantom model of multiple
      arterial disease.
AB  - The objective of this study was to evaluate in vitro the accuracy of the Doppler
      velocity ratio (VR) (intrastenotic velocity/prestenotic or poststenotic velocity)
      under different geometric conditions simulating the presence of multiple
      stenoses. A steady flow loop model was used to test the influence of the presence
      of a concentric obstruction of 84% area reduction positioned at a distance of 10,
      20 and 30 tube diameters, either proximal or distal to the stenosis under study.
      The stenosis under evaluation was either concentric or eccentric and had a
      percentage of area reduction ranging from 20% to 91%. An ultrasound color Doppler
      system was used to perform both pulsed-wave (PW) Doppler and color-flow velocity
      measurements. VRs were computed by dividing the maximum velocity of the jet by
      the velocity at 6 and 10 diameters both proximal and distal to the stenosis under
      study. A strong correlation was obtained between VR computed using color flow and
      PW Doppler velocities (r = 0.99). Results indicated that using the prestenotic
      velocity as a reference velocity generally provided a more sensitive VR index to
      grade arterial stenosis than using the poststenotic velocity. From a curve fit
      model, the measured percentages of stenosis were calculated from the VR data and
      compared to the true percentages. The correlation coefficient, r, was 0.95. When
      the proximal and distal stenoses were at 10 diameters of the stenosis
      investigated, r was 0.91, while it increased to 0.98 when the distance was 20
      diameters or more. Although VR is theoretically not influenced by hemodynamic
      factors, we demonstrated that, in practice, the presence of multiple stenoses
      reduced its sensitivity. Volumetric flow measurements are suggested to obviate
      this limitation.

PMID- 7571141
TI  - Volumetric blood flow measurement by simultaneous Doppler signal and B-mode image
      processing: a feasibility study.
AB  - A system is described for the estimation of volumetric flow in arteries in real
      time by the simultaneous processing of the audio output of a commercial
      ultrasound scanner carrying the Doppler signal, and the video output carrying B
      mode images of the lateral view of the artery. These images are processed to
      provide estimates of instantaneous internal vessel diameter. Combination with the
      relevant estimates of spatial mean velocity provides estimates of instantaneous
      volumetric flow. The major limitations of the system are the low rate of
      production of the B-mode images (17 Hz), the limited computing power and the need
      to tilt the transducer to produce an acceptably low Doppler angle. This tilting
      diminishes the quality of the imaging echoes from the arterial walls, making
      diameter measurement difficult. In principle, this approach to flow measurement
      represents an improvement on the conventional duplex technique where a single
      estimate of diameter is used. In practice, its value is limited by current
      transducer capabilities.

PMID- 7571142
TI  - Ultrasonic estimation of tissue perfusion: a stochastic approach.
AB  - Imaging of blood flow perfusion is an area of significant medical interest.
      Recently, the advantages of using the total integrated Doppler power spectrum as
      the parameter that is encoded in color has been shown to result in an
      approximately threefold increase in flow sensitivity, a relative insensitivity to
      acquisition angle and lack of aliasing. We have taken this mode a step further
      and demonstrated the potential for quantifying blood flow using correlation-based
      algorithms applied to the power signal. We show that phi(tau) = phi(0)e-VT, where
      phi(tau) is the two-time correlation of the fluctuation in the power signal, and
      v is the specific flow (reciprocal of mean transit time). Scans of a dog's blood,
      pumped at a constant rate through gum rubber tubing, were obtained using a
      Diasonics Spectra 10-MHz linear array transducer at standard range-gated spectral
      mode (PRF = 1400 Hz, wall filter = 50 Hz, sample gate = 1.5 mm). A fixed Doppler
      angle of 68 degrees was used. Five different flow rates were tested, and the
      velocities determined by power decorrelation were compared to the mean velocities
      calculated from the Doppler shifts by linear regression (R2 = 0.987). We believe
      the results are very encouraging for using power decorrelation in perfusion
      evaluation.

PMID- 7571143
TI  - A numerical and experimental investigation of the flow acceleration region
      proximal to an orifice.
AB  - Attempts to quantify valvular regurgitation have recently been focused on the
      proximal orifice flow field. A complete description of the proximal orifice flow
      field is provided in this investigation. A steady state in vitro model accessible
      by both color Doppler ultrasound (CDU) and laser Doppler velocimetry (LDV) was
      utilized. Velocities for varying flow rates and orifices were calculated by
      finite element modeling (FEM), by LDV and by CDU. The steady flow model was
      composed of circular orifices of 3, 5 and 10 mm diameters at flow rates from 0.7
      to 10 L/min. Regurgitant flow rates were calculated from the proximal CDU data by
      two separate methods. The first approach utilized angle corrected velocities
      while the second approach utilized only velocities which did not require angle
      correction (centerline velocities). Both methods correlated well with known flow
      rates (y = 0.97x -0.09, r = 0.98, SEE = 0.45, p < 0.0001; and y = 1.0x + 0.07, r
      = 0.99, SEE = 0.27, p < 0.0001, respectively) and were superior to results
      obtained by assuming a hemispherical geometry as is done in the aliasing
      technique. The methodology provides a complete analysis of the proximal flow
      field and involves fewer geometric assumptions than the aliasing approach. This
      may prove to be an advantage when analyzing in vivo flow fields with complex,
      uncertain geometry.

PMID- 7571144
TI  - Parameter mapping for the detection of disturbed blood flow.
AB  - Particularly in color flow mapping, the detection of minor stenoses is a
      significant outstanding challenge. With the goal of spatially mapping changes in
      velocity and shear rate to locate the source of the flow disturbance, two
      indicators of the magnitude of the signal correlation are presented and evaluated
      for known experimental flow conditions. A normalized parameter is presented,
      which is proportional to the magnitude of the signal correlation evaluated over a
      set of received pulses. Its performance is compared to that of a single-lag
      correlation measure for the development of spatial maps that indicate shear rate
      and velocity.

PMID- 7571145
TI  - Improved blood velocity estimation using the maximum Doppler frequency.
AB  - In vessels whose diameter is smaller than the length of the range cell or
      measurement volume, the maximum blood velocity is often calculated from the
      maximum frequency of the Doppler spectrum, using the classical Doppler equation.
      It is shown that the accuracy of this procedure is significantly improved at
      large beam-to-flow angles, if a correction for transit time broadening is made.
      This finding is based on the demonstration that the maximum frequency of the
      Doppler spectrum depends only on the maximum velocity passing through the
      measurement volume, but in a manner which is a function both of the Doppler shift
      frequency as well as the transit time broadening associated with the passage of
      scatterers through the beam width.

PMID- 7571146
TI  - Fundamental mechanical limitations on the visualization of elasticity contrast in
      elastography.
AB  - Elastography is a new ultrasonic imaging technique that produces images
      (elastograms) of the elastic properties of complaint tissue. To determine the
      Young's modulus it is necessary to measure or estimate any five of seven relevant
      variables. In elastography, the measured quantity is the normal strain component
      in the direction of the applied load, and the three normal components of stress
      may be estimated using the modified Love's analytical models while assuming a
      value close to 0.5 (incompressible) for Poisson's ratio. The distribution of
      Young's moduli can thus be computed and displayed in the form of two-dimensional
      images called elastrograms. The analytical models used for the estimation of the
      three normal components of stress assume that the target is semi-infinite and
      homogeneous in composition. The objective of this article is to determine some of
      the errors associated with the assumption of homogeneity of the target.
      Experiments using computer simulations were performed to study the efficiency
      with which elastograms display the contrast in the Young's modulus of a lesion or
      target, with respect to its background under certain conditions. It was observed
      (using the definition of contrast-transfer efficiency of elastography as the
      ratio of the elasticity contrast as measured from an elastogram, to the true
      contrast) that elastograms were consistently efficient in quantitatively
      depicting the elasticity contrast of hard lesions; however, they showed
      suboptimal contrast-transfer efficiency in cases of soft lesions in a hard
      background. In general, elastograms are efficient in displaying the elasticity
      contrast of hard or soft lesions which have a low contrast level with respect to
      the surroundings, irrespective of their size and location.

PMID- 7571147
TI  - Nonlinear behavior of a liquid containing uniform bubbles: comparison between
      theory and experiments.
AB  - Bubbles oscillating at resonance frequency dramatically enhance nonlinearity of a
      bubbly liquid. A second-order nonlinear wave equation taking account of bubble
      pulsation is solved. Numerical calculations based on the equation are compared
      favorably with experimental results. Possible biological significance of the
      highly nonlinear medium is also discussed.

PMID- 7571149
TI  - Temperature rise generated by diagnostic ultrasound in a transcranial phantom.
AB  - Temperature rises generated by diagnostic ultrasound from a modified commercial
      system (Sonos 1000 Hewlett Packard) in a transcranial phantom that consists of
      human temporal bone and tissue-mimicking material are measured. Significant
      temperature rises were found at the external and internal temporal bone surfaces.
      The experimental results are compared with cranial thermal indices (TIC)
      developed by the American Institute of Ultrasound in Medicine and the National
      Electrical Manufacturers Association for various modes. For all the modes
      compared, TIC underestimated temperature rise at the external temporal bone
      surface. The differences between the data and temperature rises predicted by TIC
      can be attributed to transducer surface heating.

PMID- 7571148
TI  - Ultrasonic heating of the brain of the fetal sheep in utero.
AB  - The fetal sheep was used as a model to determine the extent of ultrasound-induced
      heating of brain tissue in procedures involving pulsed Doppler examination of
      fetal intracranial arteries. Temperature measurements were recorded in late
      gestation fetuses insonated in utero. The centre frequency was 3.5 MHz and a
      pulse repetition rate of 6 to 10 kHz produced a power output of 0.6 or 2 W. The
      brain was insonated in the near field of a focussed beam where the -6-dB beam
      width was 1.7 cm for the 0.6-W transducers and 1.2 cm for the 2-W transducers.
      Mean (standard error) maximal temperature increases of 3.0 degrees C (0.3) and
      12.5 degrees C (1.3), respectively, were recorded in dead fetuses. The mean
      values obtained in normally perfused living fetuses were lower by 43% and 30%,
      respectively, showing that vascular perfusion substantially limited ultrasonic
      heating in sheep fetal brain tissue. There were no changes in blood flow to the
      heated brain tissue as measured using radiolabelled microspheres.

PMID- 7571150
TI  - Flow cytometric analysis of cell suspensions exposed to shock waves in the
      presence of the radical sensitive dye hydroethidine.
AB  - The occurrence of intracellularly and extracellularly generated free radicals
      during shock wave exposure on an experimental Siemens lithotripter was tested
      with the radical sensitive dyes hydroethidine and dichlorofluorescin (DCFH).
      DCFH, a nonfluorescent compound, is oxidised to dichlorfluorescein (DCF) by
      hydrogen peroxide in the presence of peroxidase. DCF green fluorescence intensity
      was used for fluorescence spectrometric measurement of hydrogen peroxide
      generated during shock-wave treatment of cell-free dye solutions. The
      fluorescence intensity of ethidium, the oxidised form of hydroethidine, was used
      for the flow-cytometric measurement of intracellular oxidising reagents present
      in RT4 tumour cells during shock-wave exposure. Changes in membrane permeability,
      which influence the intracellular content of ethidium, were controlled by
      counterstaining the cells with propidium iodide, an indicator for membrane
      integrity. We observed no increase in intracellular ethidium fluorescence
      intensity after shock-wave treatment of single cell suspensions and therefore no
      indication for shock-wave-induced intracellular free radicals.

PMID- 7571151
TI  - Glycoprotein and ganglioside changes in human trophoblasts after exposure to
      pulsed Doppler ultrasound.
AB  - Changes in glycoprotein and ganglioside composition in human trophoblasts (eighth
      week of gestation) after in vitro exposure to pulsed Doppler ultrasound (pulse
      duration 1.22 microseconds; repetition frequency 11.1 kHz; center frequency 4
      MHz; ISPPA = 175.5 W/cm2; ISPTA = 0.59 W/cm2) were investigated. Evacuated
      trophoblasts were divided in two halves and insonated for 10 min on top of a 6-cm
      layer of 5% gelatin in 50-mL tubes (Falcon) at 37 degrees C. One half of each
      trophoblast was sham insonated and served as an internal control. After
      insonation trophoblasts were maintained at 37 degrees C for 24 h. Glycoproteins
      were detected using alpha-D-mannose specific lectins from Galanthus nivalis and
      Narcissus pseudonarcissus. A decrease in the expression of mannose containing
      glycoprotein mgp47 and an increase in expression of mgp54 were observed.
      Ganglioside composition was also significantly altered. Concentrations of two
      gangliosides migrating similarly to GM2, and one similarly to GQ1, decreased by
      more than 75%. At the same time, concentrations of one ganglioside migrating
      similarly to GM3, and two other unidentified gangliosides increased two- to
      fourfold.

PMID- 7571152
TI  - Effect of ultrasound on DNA synthesis in tumor cells.
AB  - The objective of this study was to consider the influence of continuous-wave (CW)
      ultrasound (800 kHz) on DNA synthesis in Ehrlich ascitic tumor cells in vitro.
      The 10-min irradiation was carried out in rotating polyethylene tubes (5 rpm).
      Incorporation of 3H-thymidine was employed to detect DNA synthesis. Replication
      and unscheduled (repair) DNA synthesis were distinguished by means of hydroxyurea
      treatment before insonation. It was established that the use of 0.5 W/cm2 and 1.0
      W/cm2 (ISA) CW ultrasound interfered with DNA synthesis showing up as inhibition.
      The inhibition became most noticeable when starting insonation in a sample cooled
      to 5 degrees C. During insonation, the sample temperature was allowed to increase
      to the ambient (water bath) temperature of 37 degrees C. However, at an
      ultrasound intensity (SA) of 0.1 W/cm2 such inhibition was not proven, but a
      moderate stimulation of DNA synthesis was demonstrated. Changes in DNA synthesis
      after insonation were found to be transient because of a lack of stimulatory
      and/or inhibitory ultrasound effects after 1-h incubation at 37 degrees C. In our
      experimental conditions no effects on DNA synthesis due to the effects of the
      insonated medium on the cells were discernible. No statistically significant
      changes in unscheduled DNA synthesis were observed. Possible action mechanisms
      are discussed.

PMID- 7571153
TI  - [Comment on the contribution by H. Zitter, J. Poigenfurst: Evaluation of the
      mechanical properties of surgical screws using a torsion study].

PMID- 7571154
TI  - [Experiences with combined interventions on the lumbar spine].
AB  - Lumbar fusion is practicable by combined operations with dorso-ventral combined
      procedures. The indication is advisable following degenerative, inflammative,
      neoplastic processes and fractures of the spine. We operated 125 patients with
      combined procedures in 10 years. Beside dorsal instrumentation an intervention at
      the spinal canal is mostly necessary, only in 9 patients we preferred first the
      ventral part for the correction of a deformity. According to our experience the
      advantage for delayed dorso-ventral procedure is the preoperative blood donation,
      perioperative ferrum substitution and intraoperative cell saver system. In
      contrast to 1 combined procedure, most patients with 2 operations during the same
      hospital stay do not need homologous blood, the addition of time for 2 delayed
      procedures is shorter than for a single operation with intraoperative patient
      turn round in anesthesia, the convalescence was better, complications were seldom
      and hospital stay shorter. This comes out very clear in the group of lumbar
      degeneration in high age, who otherwise were bedridden for a long time following
      frequent complications.

PMID- 7571155
TI  - [Dislocation fracture of the head of the tibia. I. Results of surgical
      treatment].
AB  - Moore's classification of fracture dislocation of the tibial head gives us some
      clues of concomitant ligament injuries. We did a follow-up of 64 patients with
      fracture dislocations operated between 1982 and 1991. With these complex injuries
      we found overall unsatisfactory results regarding subjective and objective
      stability. We were able to correlate certain patterns of instability with
      specific Moore types. So a complete assessment of this complex knee-injury can be
      made from the X-ray and a stability check-up.

PMID- 7571156
TI  - [Dislocation fracture of the head of the tibia. II. Therapeutic procedure].
AB  - Fracture dislocations of the tibial plateau have associated pathology including
      ligament- and meniscus tears. They therefore require different treatment than
      split- or impression fractures. The operative and nonoperative management depends
      on the soft tissue injuries including ligament tears and depends also on the
      functional requirements of the patient. Surgical approach, operative time and
      protection of vascular supply of soft tissue and bony fragments are the main
      factors influencing postoperative complications and outcome. The different
      fracture dislocation types according to the Moore classification require specific
      types of treatment. This includes open reduction with internal or external
      fixation as well as arthroscopy.

PMID- 7571157
TI  - [Proximal humerus shaft fracture as a complication after keyhole-plasty. A case
      report].
AB  - Six weeks after operative treatment of a rupture of the long head of biceps
      brachii using keyhole tenodesis on the left arm in a man 69 years old a fracture
      of the upper arm happened. The reason seems to be the localization of keyhole
      osteotomy being probably to much distal.

PMID- 7571158
TI  - [Inlay dislocations after primary, cement-free hip joint replacement].
AB  - This report deals with diagnostic effort of dislocated acetabular cup inlay in
      cementless total hip-arthroplasty. The metallic sound caused by collision of the
      ceramic head and metal acetabular component is documented by CTG. Suggestions of
      incidence and prevention of later inlay-dislocations during primary implantation
      are given.

PMID- 7571159
TI  - [What can the hospital deliver? What must the hospital deliver?].

PMID- 7571161
TI  - Charge structure of the glomerular capillary membrane.

PMID- 7571160
TI  - A short survey of the scientific work of Torsten Teorell.

PMID- 7571162
TI  - Red blood cells, phase contrast, interference contrast microscopy and
      microspectrophotometry.
AB  - Following Teorell's (1) observation that the ghosts of hypotonically hemolysed
      erythrocytes reseal, it was shown that during the time they are permeable to
      hemoglobin, foreign macromolecules (dextran) can enter and that the hemolysed
      cell can achieve a final colloid-osmotic equilibrial state containing dextran and
      some residual Hb. In this way dextran reduces the hemoglobin loss in hypotonic
      hemolysis. Some hemoglobin loss is, however, inevitable, as it begins with a non
      diffusive bulk outflow, sometimes observable as a jet, during which time a
      diffusive influx of the colloid-osmotic "balancer", dextran, is not possible.
      Finally, as expected from a process which is for the most part diffusive,
      transmembrane macromolecular transport is bidirectional; during hemolysis smaller
      molecules escape to a greater extent than larger ones.

PMID- 7571163
TI  - Torsten Teorell, the father of pharmacokinetics.

PMID- 7571164
TI  - A daughter's reflections upon her father's creativity.

PMID- 7571165
TI  - Torsten Teorell, the teacher and researcher.

PMID- 7571166
TI  - Effect of indomethacin on thrombin-induced pulmonary edema in the rat.
AB  - The preventive effect of indomethacin on thrombin-induced pulmonary edema was
      studied in rats. Administration of thrombin caused a significant increase in lung
      weight, wet weight to dry weight ratio (WW/DW), and relative lung water content.
      During infusion of thrombin, mean pulmonary artery pressure rose and mean
      systemic artery pressure fell, PaO2 decreased progressively and there was a
      continuous rise in pH and PaCO2. An inhibitor of cyclooxygenase, indomethacin, at
      a dose of 1 mg/kg body weight, induced a significant further increase in lung
      weight (p < 0.05), and a tendency towards an increase in WW/DW and water content
      compared with animals given thrombin alone. Treatment with indomethacin, however,
      counteracted the elevated pulmonary artery pressure occurring in the early phase
      after thrombin infusion, but not that in the late phase. Systemic artery pressure
      was not affected by indomethacin. The increases in pH and PaCO2 after thrombin
      infusion were attenuated and remained stable almost at baseline level after
      indomethacin administration. Indomethacin did not prevent the hypoxemia induced
      by thrombin infusion. In conclusion, although indomethacin prevented the early
      increase in pulmonary artery pressure due to thrombin and the decrease in pH and
      the increase in PaCO2, it caused lung vascular permeability to protein to
      increase more than with thrombin alone.

PMID- 7571167
TI  - The significance of an across-shift decrease in vital capacity--a re-analysis of
      a study on subjects exposed to diesel exhaust.
AB  - Occupational exposure to diesel exhaust may develop acute as well as chronic lung
      function impairment. In this study, data from an earlier study on a group of
      subjects working at tunnel construction site were analyzed. The aim of the
      analysis was to examine the significance of an across-shift decrease in vital
      capacity with concern to other lung physiological measurements. There were no
      statistically significant differences, either in the average age, time of
      employment, vital capacity before a working shift after two days of no exposure,
      or the distributions of smoking habits and respiratory symptoms, between the
      eight workers who had an across-shift decrease in vital capacity and the five
      workers who had not. Subjects with an across-shift decrease in vital capacity had
      a significantly greater across-shift decrease in residual volume and total lung
      capacity than subjects without an across-shift decrease in vital capacity. The
      pathophysiological mechanisms for this across-shift decrease in residual volume
      is not fully understood. However, an altered defence mechanism in the lung may
      play a role for a prolonged retention time for the particles in the inhaled
      diesel exhaust, resulting in the across-shift decrease in residual volume. The
      results thus suggest that measurements of across-shift vital capacity is of
      importance in identifying susceptible subjects with occupational exposure to
      diesel exhaust.

PMID- 7571168
TI  - Treatment of acute renal failure in intensive care patients by continuous
      arteriovenous hemofiltration (CAVH): two years' experience in two centres.
AB  - The study objective was to evaluate the outcome of continuous arteriovenous
      hemofiltration (CAVH) as a first choice treatment for acute renal failure (ARF)
      in critically ill intensive care patients in two centres with a long experience
      in the field of continuous renal replacement therapies. Sixty consecutive
      intensive-care ARF patients from Uppsala Centre and 71 consecutive ARF patients
      from Vicenza Centre were included during a period of two years. Their age range
      was 58 +/- 16 and 52 +/- 15 years in Uppsala and Vicenza, respectively. CAVH was
      performed in the postdilution form using different types of hemofilters. Three
      choices of vascular access were utilised in each centre, namely: the Buselmeier
      shunt, femoral vessel catheter and the Scribner shunt. The pre-treatment serum
      urea level (mean +/- SD) in the Uppsala patients (30 +/- 14 mmol/l) was
      significantly higher (p < 0.001) than that of the Vicenza patients (17 +/- 10
      mmol/l). The Uppsala patients had a longer treatment duration than the Vicenza
      patients; 8 +/- 6 vs 5 +/- 5 days (p < 0.05) perhaps because they were much older
      than the Vicenza patients (p < 0.05) in addition to their multi-organ failure.
      However, the total outcome of CAVH in the two centers was not significantly
      different (52 and 58% patient's survival in Uppsala and Vicenza,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571169
TI  - A clinical method for measuring the distribution of segmental flexion mobility in
      the cervico-thoracic spine.
AB  - The aim of this study was to evaluate the validity and the repeatability of a new
      technique to assess segmental flexion mobility in the cervico-thoracic spine
      between segments C7 and T5. The new technique is referred to as the Cervico
      Thoracic-Ratio (the CTR-technique). The radiological evaluation of skin
      distraction measurements showed that validity was high for the CTR-technique. A
      high correlation between vertebral flexion mobility and skin distraction was
      recognized individually and for the whole group. The evaluation of repeatability
      was found to be high for intratester and fair for intertester repeatability. The
      CTR-technique may become a valuable complement to other methods for assessing
      segmental flexion mobility in patients suffering from neck-shoulder pain in
      clinical practice.

PMID- 7571170
TI  - Effects of oral endotracheal intubation on metabolic gas exchange (short
      communication).

PMID- 7571171
TI  - A pilot study of the effects of abdominal aortic cross clamping on metabolic gas
      exchange (short communication).

PMID- 7571172
TI  - Graft-versus-host reaction and rejection after experimental small-bowel
      transplantation. Minireview based on a doctoral thesis.

PMID- 7571176
TI  - Second in situ extracorporeal shock wave lithotripsy in not disintegrated
      ureteral stones is preferred to retrograde manipulation.
AB  - In this study we tried to determine the optimal treatment of upper ureteral
      stones which are not disintegrated by the first extracorporeal shock wave
      lithotripsy (ESWL) and to analyze the cost-benefit ratio of retrograde
      manipulation into the renal pelvis. 180 patients with an upper ureteral stone
      were treated by ESWL in situ. 40 patients needed a retreatment and were
      randomized for retrograde manipulation before ESWL or ESWL in situ without a
      prior manipulation. In both the in situ group and in the push-and-smash group,
      the stone-free rate was 75%. In stones < 8 mm, the disintegration rate was higher
      after retrograde manipulation into the renal pelvis and inserting a DJ catheter.
      In conclusion, ESWL in situ is the optimal treatment for all patients with upper
      ureteral stones. We reserve retrograde manipulation before a second ESWL for
      stones < 8 mm. Routinely employed auxiliary procedures such as placement of a DJ
      catheter increase the costs significantly, without improving the results.

PMID- 7571173
TI  - Early management after acute traumatic spinal cord injury.

PMID- 7571175
TI  - Extracorporeal shockwave therapy for urolithiasis with renal insufficiency.
AB  - Management of urolithiasis with renal insufficiency poses a multidimensional
      nephrourological situation. Sixty-two patients of potentially reversible calculus
      obstructive nephropathy and azotemia were treated with extracorporeal shockwave
      lithotripsy (ESWL) on the Sieman's Lithostar. These patients were treated under
      sedoanalgesia after the initial therapeutic ureteral stenting. Satisfactory
      fragmentation was achieved in all the patients. The incidence of major
      complications was 3.2% with an 85% stone-free rate at 6 months. Pre- and post
      ESWL hemodialysis was required in 14 and 3 patients, respectively. All patients
      had variable levels of improvement in the renal function. Proper selection of
      cases is mandatory for satisfactory outcome. The combination of ureteral stenting
      followed by phased ESWL represents an attractive alternative to traditional
      surgical management of stones with renal insufficiency.

PMID- 7571174
TI  - Treatment of human renal cell carcinoma with high-energy shock waves--a new in
      vivo/in vitro model.
AB  - The effects of high-energy shock waves (HESW) on the human renal cell carcinoma
      were examined. The kidneys were available from 32 patients treated by radical
      nephrectomy due to renal cell carcinoma. Immediately after nephrectomy the
      kidneys were perfused with cold HTK solution and stored for a maximum of 4 h in
      hypothermia at 8 degrees C. The tumors were treated with 4,000 shocks (65 mPa =
      0.6 mJ/mm2) in an electromagnetic lithotriptor (Siemens Co., Erlangen, Germany).
      Microscopic and immunohistological examinations of the tumors were performed
      after treatment, and cell proliferation rates of treated and untreated specimens
      were analyzed by cell cultures in 10 cases. HESW induce severe microscopic damage
      in the tumor tissue as complete rupture of the vessel walls and destruction of
      the tubular-formed tumor masses in the focal area. Immunohistochemistry shows
      intact immune reactive endothelial cells by factor 8-associated antibodies until
      the border to histological damage. Around this region a zone of negative antibody
      reaction against collagen type 4 is found. In cell cultures the proliferation
      rates of treated specimens were significantly lower compared to untreated. The
      human renal cell carcinoma seems to be susceptible for treatment with shock
      waves. HESW induce direct damage of tumor cells and vascular damage in the tumor
      which may be the primary cause of tumor necrosis.

PMID- 7571177
TI  - The Swiss lithoclast: an ideal intracorporeal lithotripter.
AB  - We report our early experience with a new device for endoscopic stone
      disintegration: the Swiss lithoclast. This device was used to treat 200 patients
      with stones in kidney, ureter, and bladder. Its effectiveness was 100% when the
      stone could be approached irrespective of size or composition, and no
      complication was encountered.

PMID- 7571178
TI  - Subcapsular hematoma due to ESWL: risk factors. A study of 4,247 patients.
AB  - A study of 4,247 shockwave lithotripsy treatment was performed to identify and
      analyze the risk factors for the development of post-extracorporeal shock-wave
      lithotropsy hematomas. The Dornier HM-3 and HM-4 lithotriptors were used. We
      recognized 23 hematomas in 23 patients (0.54%). Various factors were examined to
      identify the certain predisposing risk factors. There was no correlation of sex,
      age, stone number, stone size, stone location, number of shock waves and voltage
      used with the occurrence rate of hematoma. We found that patients with pre
      existing hypertension and especially those with poor control of it had a
      significantly increased incidence of perinephric hematoma.

PMID- 7571179
TI  - Cryptorchidism and marker chromosomes: identification of marker chromosomes by
      fluorescence in situ hybridization.
AB  - Identification of marker chromosomes by fluorescence in situ hybridization was
      performed in 2 cases of cryptorchidism. In case 1, the marker chromosome was
      derived from chromosome 22. In case 2, the origin of the marker was the
      centromere of chromosome 8. The extent of the congenital anomalies in these cases
      was milder than that in cases with complete trisomy of an autosome. These
      findings suggest that an incomplete extra autosome might influence clinical
      characteristics.

PMID- 7571180
TI  - Reconstruction of the urethral meatus with a buccal mucosa graft.
AB  - A buccal mucosa graft from the lower lip was used for meatal reconstruction in 3
      patients. The buccal mucosa graft was combined with a bladder mucosa graft for
      urethral substitution in 1 adult and 1 child, and was anastomosed to a skin tube
      for creating a glanular urethra in 1 child. The buccal mucosa graft obtained was
      approximately twice as wide as the desired urethra. Postoperatively the buccal
      mucosa graft became shrunken at the proximal anastomosis and urethral stricture
      developed in 2 children. The graft did not shrink at the meatus, but the meatus
      became widened in 2 patients. These results suggest that a buccal mucosa graft is
      useful for meatal reconstruction, but further technical improvement is necessary
      to avoid postoperative complications.

PMID- 7571181
TI  - Squamous cell carcinoma of the ureter with marked leukocytosis producing
      granulocyte colony-stimulating factor.
AB  - This paper describes a case of squamous cell carcinoma (SCC) of the ureter which
      showed marked leukocytosis without any evidence of infection and hematologic
      malignancies. The level of serum granulocyte colony-stimulating factor (G-CSF)
      assayed by enzyme immunoassay increased and the immunohistochemical staining of
      the ureter tumor showed the presence of G-CSF in tumor cells. These findings
      indicate that SCC of the ureter produced G-CSF which stimulated leukocyte
      production in bone marrow and resulted in leukocytosis. To our knowledge, this is
      the first report of ureter tumor with leukocytosis producing G-CSF.

PMID- 7571182
TI  - Primary signet ring cell carcinoma of the urinary bladder. Review of the
      literature and report of two cases.
AB  - The signet ring cell carcinoma of the urinary bladder is a rare neoplasm; the 70
      cases found in the literature pursued a fulminant and mostly fatal course; the
      neoplasms diffusely invaded the bladder wall without forming intraluminal growths
      and could not be controlled by segmental resection, radiotherapy and chemotherapy
      alone or in combination. We herewith present 2 cases of primary signet ring cell
      carcinoma of the urinary bladder--one associated with high-grade transitional
      cell carcinoma and in situ carcinoma--and review the literature.

PMID- 7571183
TI  - Prostate cancer-induced oncogenic hypophosphatemic osteomalacia.
AB  - A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl,
      marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of
      phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25
      (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase
      of relative osteoid volume and fractional formation rate in the undecalcified
      section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of
      1,25 (OH)2D production and phosphaturia was suggested.

PMID- 7571184
TI  - Bilateral metachronous testicular germ cell tumors occurring in two non-twin
      brothers. Case report and review of the literature.
AB  - We report here the familial occurrence of bilateral testicular germ cell tumors
      in 2 non-twin brothers, developing after an interval of 16 and 4 years,
      respectively. To our knowledge, this is the first report on the occurrence of
      metachronous and bilateral testicular tumors in non-twin brothers.

PMID- 7571185
TI  - Cryptorchidism and extragonadal germ cell tumor.
AB  - A patient with an extragonadal germ cell tumor and a history of bilateral
      cryptorchidism is reported. The rarity of this concurrence in a single patient is
      discussed. The necessity for thorough investigation of the cryptorchid testes in
      patients with metastatic germ cell cancer remains essential.

PMID- 7571186
TI  - Successful renal autotransplantation with Y-prosthetic aortic replacement in a
      patient with complete occlusion of abdominal aorta and renal artery.
AB  - Occlusion of the abdominal aorta represents the end stage of an atherosclerotic
      process and often is associated with stenosis of renal artery inducing renal
      failure and hypertension. Surgical and medical treatments are indicated to
      preserve and restore renal function in patients with these conditions. We report
      herein the first successful renal autotransplantation combined with aortic
      replacement by Y prosthesis in a patient with complete occlusion of abdominal
      aorta and bilateral renal arteries, resulting in limb-threatening ischemia and
      progressive renal failure.

PMID- 7571187
TI  - Donor-gifted allograft lithiasis: extracorporeal shockwave lithotripsy with over
      table module using the Lithostar Plus.
AB  - Allograft lithiasis is usually secondary. Donor-graft lithiasis is a rare cause
      and only 5 cases have been reported. We report 2 such cases which are the first
      in the live-related transplantation programme. The pressing need to increase the
      donor pool in developing countries, safety of therapy in graft lithiasis coupled
      with minimal estimated risk of lithiasis recurrence in the donor are the main
      justifications for accepting calculi bearing kidney for transplantation. The 2
      cases underwent extracorporeal shockwave lithotripsy using the overhead table
      module of the Lithostar Plus. The technical ease of lithotripsy using an on-line
      ultrasound module in these 'ectopically' placed kidneys is discussed. The effect
      of shockwaves on allograft function was studied by a pre- and post-renal scan
      (99Tc-DTPA) and serum creatinine. No adverse effect of shockwave on allograft
      function was noted both on short- and long-term follow-up.

PMID- 7571188
TI  - Spontaneous kidney rupture--symptom of renal tumors.
AB  - Spontaneous ruptures of the kidney frequently require an emergency surgical
      intervention and the underlying pathology often only becomes clear
      intraoperatively. On the basis of our own cases the clinical management of the
      symptom 'rupture of the kidney' is discussed particularly referring to renal
      tumors.

PMID- 7571189
TI  - Osteopontin mRNA in the kidney on an experimental rat model of renal stone
      formation without renal failure.
AB  - We had sequenced a cDNA of calcium oxalate urinary stone protein extracted with
      0.1 M EDTA. cDNA sequences showed complete homology between urinary stone protein
      and human osteopontin (OPN, bone sialoprotein I). In the present study, we
      investigated the expression of OPN mRNA in the rat kidney in an experimental
      model of renal stone formation using glyoxylic acid and 1,25-dihydroxyvitamin D3
      (D3). In the renal stone formation model with and without renal failure, OPN mRNA
      was shown to be localized by in situ hybridization using an OPN cRNA probe mainly
      in the distal convoluted tubule of the kidney, and was enhanced compared with the
      normal control which was sporadically positive. By Northern blot analysis, the
      expression of OPN mRNA was shown to be increased by about 5.2-fold in the renal
      stone formation model and 2.3-fold in D3-administered rats compared with
      controls. However, no change in the expression of OPN mRNA was observed in an
      acute renal failure model induced by gentamicin or in rats administered
      glycoxylic acid alone. Therefore, the promotion of OPN mRNA expression was
      intrinsic to this stone formation model, and not secondary to acute renal failure
      because of obstruction by microcrystals in the renal tubules or gentamicin.

PMID- 7571190
TI  - Renal abscess due to Aspergillus fumigatus in a patient with the acquired
      immunodeficiency syndrome.
AB  - Disseminated aspergillosis is a systemic fungal infection that may occur in
      previously healthy or immunocompromised patients. The condition, although rare,
      is being recognized with increasing frequency in persons with the human
      immunodeficiency virus. Clinical genitourinary involvement is unusual. We present
      a case of renal abscess for Aspergillus fumigatus in a patient with acquired
      immunodeficiency syndrome who complained of flank pain and fever.

PMID- 7571191
TI  - [The characteristics of bacteriuria in urological infections].
AB  - Bacteriological examination of the urine from 1138 elderly patients (50-80 years
      of age) with urogenital inflammation determined the predominant contamination of
      the urine with gram-negative opportunistic agents in titers 10(3)-10(7) CFU/ml.
      Bacteriuria arose due to primarily monocultures represented most commonly with E.
      coli and Ps. aeruginosa. Associated and two- three-component microflora comprised
      mainly S. epidermidis and S. faecalis. The degree of bacteriuria in elderly
      patients made up 10(5)-10(7) CFU/ml and 10(3)-10(7) CFU/ml in 69.6% and 30.4% of
      patients, respectively.

PMID- 7571192
TI  - [The cytology of the urinary sediment in the differential diagnosis of the
      complications in patients with kidney allografts].
AB  - Urine sediment from 56 renal transplant recipients was tested cytologically. The
      recipients had 7 episodes of acute rejection (AR), 8 episodes of cyclosporin
      nephrotoxicity (CNT), acute tubular necrosis (ATN), combined complications,
      bacterial infection in 11, 6 and 16 cases, respectively. 12 patients had stable
      renal function. Cytospin preparations were made for Pappenheim staining. FACScan
      cytograms were obtained based on light scattering (cell size and granularity).
      Low cell count in patients with stable renal function and higher levels of
      mononuclear cells in all cases of a complicated postoperative period were seen.
      In acute tubular necrosis the sediment had a high scatter pattern, i.e. high
      density and large particles, while in cyclosporin nephrotoxicity renal epithelial
      cells had a low scatter pattern. Polymorphs were typical of the bacterial
      infection and acute tubular necrosis. Acute rejections were associated with
      elevated lymphocyte number. Microscopic examination revealed predominance of
      collect duct cells, lymphocytes with morphological signs of activation in acute
      rejection and proximal tubular cells in cyclosporin nephrotoxicity. Episodes of
      combined complications were difficult for diagnosis due to their mixed
      cellularity.

PMID- 7571193
TI  - [Platelet aggregation and the fibronectin level of the blood in children with
      chronic glomerulonephritis].
AB  - We compared platelet aggregation with changes in fibronectin (FN) plasma levels
      in children with various forms of primary CGN. We found that a rise in platelet
      aggregation and plasma FN level depends on CGN clinical form, extent of
      inflammation and sclerotic changes in nephric tissue. The greatest changes
      occurred in patients with nephrotic CGN and with segmentary glomerulosclerosis.

PMID- 7571195
TI  - [Pyeloureteral anastomosis in kidney transplantation].
AB  - Urological complications of kidney transplantation remain a serious postoperative
      problem. They occur in 2-10% of cases. The authors present the data on 102
      cadaveric and 74 syngenesioplastic transplantations of the kidney. 70 patients
      underwent surgery according to the alternative technique with ipsilateral
      nephrectomy and establishment of pyeloureteroanastomosis. Urological
      complications, lethal outcomes, destruction of the transplant occurred in 9.77,
      11.11, 55.6% of the patients, respectively. Application of
      pyeloureteroanastomosis entailed complications in 4.28%, of ureteroneocystostoma
      in 13%, pyelopyeloanastomosis in 2 cases of 4. In urological complications
      pyeloureteroanastomosis often is the only feasible reconstructive operation
      saving the transplant. Its advantages make it treatment of choice in primary
      reconstruction of the urinary tracts in kidney transplant recipients with
      relatively low risk of urological complications.

PMID- 7571194
TI  - [Urolithiasis in children].
AB  - The paper reviews the experience of the urological clinic in the treatment of 106
      children with urolithiasis. The necessity of careful pretreatment examination to
      reject associated anomaly of the upper urinary tracts as a cause of lithogenesis
      is emphasized. Surgical treatment and extracorporeal lithotripsy which has proved
      highly effective against uroliths in children are considered.

PMID- 7571196
TI  - [Experimental and clinical studies of methods for regenerating the dialysis
      solution].
AB  - The efficacy of artificial kidney apparatuses was assessed by using 5 different
      methods of regenerating the dialysis solution. In the series of model experiments
      the authors have studied the quality of the solution purification from urea,
      creatinine, uric acid, nonorganic phosphorus and potassium ions. Clinical trial
      of the regeneration systems was performed in patients with chronic renal failure
      on preparation for renal transplantation. The efficacy of the regeneration
      systems by elimination from the blood of metabolic products was not inferior to
      the standard hemodialysis system working in the discharge mode. The most
      promising method was that of electrochemical regeneration of the dialysis
      solution.

PMID- 7571197
TI  - [Anuria following extracorporeal lithotripsy].
AB  - Of 500 extracorporeal lithotripsies performed by the authors anuria arose in 2
      cases on postlithotripsy days 3 and 5. There was also systemic intoxication of
      unclear origin.

PMID- 7571198
TI  - [Transurethral endoscopic dissection of the bladder neck and prostate].
AB  - Transurethral endoscopic incision of the neck of the bladder and the prostate was
      conducted for elimination of infravesical obstruction due to benign prostatic
      hyperplasia (BPH) of a small size and sclerosis of the bladder neck or prostate.
      37 patients aged 22-85 years were treated: 17 had BPH and 20 had bladder neck
      sclerosis (primary in 2 and secondary in 18 patients). In 4 cases the incision
      was combined with internal urethrotomy, in 4 with cystolithotripsy and in 2 with
      transurethral resection of the bladder. The diagnosis was made basing on routine
      blood counts, urinalysis, x-ray, ultrasonic, uroflowmetry and pathomorphological
      investigations. The last stage of the examination was urethrocystoscopy made
      shortly before operation. The symptoms were evaluated according to answers in the
      J-PSS questionnaire. Anesthesia was only intravenous or epidural. A spicular
      Collins electrode cut at 5 and 7 of the assumed dial. After hemostasis an
      urethral catheter was inserted for 24-48 hours. The intervention lasted 15
      minutes, no lethal outcomes occurred. Marked symptomatic improvement was achieved
      in 36 patients (97%). BPH cut was uneffective in one patient who subsequently
      underwent transurethral resection.

PMID- 7571199
TI  - [A trial of the use of finasteride and terazosin in patients with benign
      prostatic hyperplasia].
AB  - 94 patients with obstructive urination due to benign prostatic hyperplasia
      received finasteride (proscar), inhibitor of 5 alpha-reductase, in a single dose
      5 mg and terazosine, alpha 1 adrenoblocker, in a daily dose of 9.7 mg/day. The
      follow-up averaged 16.1 months. As shown by overall score of the symptoms and
      quality of life, rectal and ultrasonic examinations, uroflowmetry, the prostate
      decreased by 17%, on the average in 72% of the patients. Subjectively, urination
      has also improved. Maximal flow rate elevated by 55% in the majority of patients.
      Combination of finasterine with terazosine is well tolerated and proved optimal
      as a conservative therapy in patients with obstructive urination as a result of
      benign prostatic hyperplasia.

PMID- 7571200
TI  - [Prostaglandin E1 in the diagnosis and therapy of erectile disorders].
AB  - Intracavernous injections (ICI) of prostaglandin E1 (PGE1) of German produce
      (Schwarz Pharma A. G.) have been tested for diagnosis of erectile disorders in 63
      patients (age 32-71, the majority at the age 45-65) and for autotherapy in 22
      patients. In 76% of males with erectile impotency PGE1 ICI in a dose 10-20
      micrograms result in marked erection which emerged within 5-15 min after the
      injection and persisted for 90 min on the average in spite of ejaculation. 86% of
      patients suffering from erectile dysfunction found this method of impotency
      correction satisfactory as it warrants normal coitus in 91% of cases (dose
      regimen 10-20 micrograms). ICI of PGE1 in the above dose 1-2 times a week for 2
      months is safe, entail no systemic and insignificant local side effects. The risk
      of priapism and cavernous body fibrosis is minimal. The duration of the effect is
      related to the dose. The above advantages make PGE1 superior to papaverin and
      phentolamine. PGE1 ICI are recommended as the treatment of choice for therapy of
      erectile dysfunctions.

PMID- 7571201
TI  - [Anejaculation: its etiology and pathogenesis, classification and clinical
      aspects].
AB  - 43 patients suffering from anejaculation were treated in 1983-1993 in the
      department of andrology of the N. A. Semashko Medical Institute urological
      clinic. Most commonly anejaculation is caused by prostatic and bladder neck
      surgery (25.6%), diabetes mellitus (18.6%) and presents as retrograde
      ejaculation, impaired sperm emission into the urethra, aspermatism (51.2, 27.9,
      20.9% of patients, respectively). The leading pathogenetic factors are peripheral
      neuropathy, surgical injury to the bladder internal sphincter, psychosexual
      disorders. The authors propose classification and algorithm of the patients'
      examination to facilitate and enhance diagnosis. Special attention should be
      given to the presence or absence of orgasm, after-orgasm occurrence of
      spermatozoa in urine. Anejaculation treatment outcomes remain unsatisfactory.
      Good responses were achieved with selective adrenomimetic gutron, laser therapy
      and electrovibration. Prevention of anejaculation should be given more attention.

PMID- 7571202
TI  - [The etiological factors in pyelonephritis occurring against a background of
      nephrolithiasis].
AB  - 656 urine and 78 blood samples were examined immunomicrobiologically. No
      bacterial growth was recorded in 43.8% of urine samples. Opportunistic bacteria
      were represented by Enterobacteriaceae, nonfermenting gram-negative bacteria with
      predominance of E. coli, P. mirabilis, P. aeruginosa isolated both in
      monocultures and in associations in conventional diagnostic titers (1g 5 CFU/ml).
      Throughout 40 days of the hospital stay microflora continuously changed, but
      until the discharge the infection persisted. The study of the immunological
      aspect of anti-infection resistance showed that most of the examinees (73%) at
      admission with pyelonephritis exacerbation have deficient cellular and humoral
      defense.

PMID- 7571203
TI  - ["Nephrogenic adenoma" of the bladder].

PMID- 7571205
TI  - [Chronic cystitis].

PMID- 7571204
TI  - [Percutaneous surgical interventions and extracorporeal lithotripsy in the
      treatment of the urological complications after a kidney transplant].

PMID- 7571206
TI  - [The pathogenesis and prevention of urinary tract infection in women].
AB  - Urinary tract infection (UTI) in females occurs significantly more frequently
      than in males because of specific anatomical and functional features of female
      urinary system, sequelae of pregnancy, delivery, gynecological diseases. Much
      controversy still exists as to pathogenesis of UTI and UTI-induced urinary
      inflammation. We have examined 233 females of different age with UTI and obtained
      evidence which shows participation of such factors as early and intensive sex,
      ignorance of sex hygiene, multiple pregnancies, deliveries, abortions,
      inflammatory gynecological diseases, anogenital infection in its pathogenesis.
      These factors were registered 2-4 times more frequently in UTI females than in
      controls without UTI. Bacteriological urinary and genital findings coincide in
      80% of cases in terms of an infective agent. This suggests that it is essential
      to detect urogenital infection in girls and females as early as possible and to
      treat it adequately with antibacterial and other drugs. The leading role of an
      ascending urinogenic route in urinary tract infection from local sources in
      anogenital zone, sexual factor and the absence of relevant hygienic habits proved
      most contributing to UTI pathogenesis. This concept serves the basis for UTI
      prevention in females.

PMID- 7571207
TI  - Experimental point spread function of fm pulse imaging scheme.
AB  - In this paper, we have examined the possibility of incorporating pulse
      compression techniques into a conventional medical B-scan imaging scheme. Linear
      frequency modulation fm, one form of pulse coding among many others, has been
      used in this study. With this approach, one can overcome current peak intensity
      limitations. A theoretical framework that includes medium propagation effects,
      transducer bandwidth and diffraction effects is presented, which could be used to
      examine the system point spread function under this imaging scheme. A prototype
      experimental set-up and signal processing are described and used for simple
      imaging tasks in attenuating and nonattenuating media. Analysis of the
      experimental point spread functions shows that resolution similar to conventional
      short pulse imaging can be achieved. However, the existence of large range side
      lobe levels usually associated with pulse compression processing can degrade
      contrast resolution in medical ultrasound. We have considered various different
      factors that can affect the range side lobe levels and examined their effect
      either experimentally or through simulations. The technique has the potential for
      improving signal-to-noise ratio (SNR), maximum penetration depth and resolution
      without exceeding peak intensity limitations. Some possible applications are
      discussed that merit further evaluation. Our work demonstrates the feasibility of
      this technique and presents a theoretical framework that can be used in future
      studies aimed at evaluating image quality, system performance, and possible
      artifacts under such an imaging scheme.

PMID- 7571208
TI  - Methods for estimation of subsample time delays of digitized echo signals.
AB  - Time delay estimation (TDE) is commonly performed in practice by crosscorrelation
      of digitized echo signals. Since time delays are generally not integral multiples
      of the sampling period, the location of the largest sample of the
      crosscorrelation function (ccf) is an inexact estimator of the location of the
      peak. Therefore, one must interpolate between the samples of the ccf to improve
      the estimation precision. Using theory and simulations, we review and compare the
      performance of several methods for interpolation of the ccf. The maximum
      likelihood approach to interpolation is the application of a reconstruction
      filter to the discrete ccf. However, this method can only be approximated in
      practice and can be computationally intensive. For these reasons, a simple method
      is widely used that involves fitting a parabola (or other curve) to samples of
      the ccf in the neighborhood of its peak. We describe and compare two curve
      fitting methods: parabolic and cosine interpolation. Curve-fitting interpolation
      can yield biased time-delay estimates, which may preclude the use of these
      methods in some applications. The artifactual effect of these bias errors on
      elasticity imaging by elastography is discussed. We demonstrate that
      reconstructive interpolation is unbiased. An iterative implementation of the
      reconstruction procedure is proposed that can reduce the computation time
      significantly.

PMID- 7571209
TI  - Experimental studies on an efficient catheter array imaging system.
AB  - A new synthetic aperture system for intraluminal imaging has been tested using a
      32 element, 20 MHz circular array wrapped around the surface of a catheter
      appropriate for coronary artery applications. This system is based on an optimal
      reconstruction method that has been extended to reduce grating lobes using a
      slight modification to classic synthetic aperture data acquisition. Optimal
      reconstruction filters have been derived for two different operating modes based
      on this new data acquisition strategy. Imaging results on a wire target phantom
      show that spatial resolution is a simple linear function of depth, reaching a
      minimum 6 dB beam width of approximately 2.2 wavelengths. Sidelobe levels are
      inherently high for this system because of the small number of firings used to
      synthesize an aperture. Optimal reconstruction filters, however, can reduce these
      sidelobes to at least -20 dB in all cases. Finally, images of an excised segment
      of porcine femoral artery demonstrate the overall performance of the system as an
      intraluminal imager.

PMID- 7571210
TI  - Optimization of signal-to-noise ratio for multilayer PZT transducers.
AB  - In medical ultrasound imaging, two-dimensional (2-D) array transducers are
      desirable to implement dynamic focusing and phase aberration correction in two
      dimensions as well as volumetric imaging. Unfortunately, the small size of a 2-D
      array element results in a small clamped capacitance and a large electrical
      impedance near the resonance frequency. This results in poor signal-to-noise
      ratio (SNR) of the array elements. It has previously been demonstrated that
      transducers made from multilayer PZT ceramics have lower electrical impedance and
      greater SNR than comparable single layer elements. A simplified circuit model has
      been developed to optimize the SNR for multilayer ceramic (MLC) transducers. In
      this model, an electronic transmitter excites the array element and in the
      receive mode, the element drives a coaxial cable load terminated by a high
      impedance preamplifier. The transducer impedance is Zt/N2, where N is the number
      of piezoelectric layers. Maximum transmit signal is obtained when N = Ntx such
      that the transducer impedance, Zt/Ntx2, is matched to the source impedance.
      Maximum receive signal is obtained when N = Nrx such that the transducer
      impedance, Zt/Nrx2, is matched to the coaxial cable reactance. For maximum pulse
      echo signal, the transducer should be designed with N = square root of Ntx Nrx,
      the geometric mean of Ntx and Nrx. Using this optimization technique, a 1.5-D
      array was designed with 3 layers for maximum pulse-echo SNR. Results of
      simulations from the simplified circuit analysis were consistent with those of
      the KLM model. The 3 layer array was fabricated as well as a single layer control
      array. The measured transmit signal and receive signal agreed with the simulation
      results.

PMID- 7571212
TI  - Hemospermia: diagnosis and management.

PMID- 7571211
TI  - Should Medicare provide reimbursement for prostate-specific antigen testing for
      early detection of prostate cancer? Part IV: Estimating the risks and benefits of
      an early detection program.

PMID- 7571213
TI  - Adenocarcinoma of the rete testis.
AB  - To date, no studies have evaluated adenocarcinoma of the rete testis
      statistically, because reports have been limited to single cases or series of 2
      cases only. Univariate and multivariate analyses on disease-free survival have
      been performed after combining all data available in the literature with our own.
      Information about disease-free survival has been collected in 38 patients. As
      many as 40% of them died within the first year of diagnosis. Three and 5-year
      disease-free survival was 49% and 13%, respectively. We have not detected any
      difference in survival between age groups or side of the lesion. Similarly,
      statistical difference cannot be proved between survival of tumors with nodular
      infiltrating or cystic growth pattern, although it has been suggested that these
      two varieties represent different tumor types from a gross and microscopic
      morphologic point of view. Univariate analysis reveals that tumor stage, tumor
      size, and therapy may have an influence on survival. Tumors that are organ
      confined and small lesions (testicular mass < 5 cm in maximum diameter) behave
      definitely better than those disseminated at diagnosis or of a bigger size.
      Surprisingly, tumor size is not associated with tumor stage or histologic growth
      pattern (nodular infiltrating versus predominantly cystic). With regard to
      therapy, cases in which RPLND has been performed as part of the therapy behave
      better in univariate analysis, while patients who receive radiation do worse.
      Most probably these facts reflect that patients with clearly advanced disease
      where local control cannot be achieved by surgery tend to undergo palliative
      treatment by radiation. On the other hand, RPLND tends to be performed in
      patients in whom there is no evidence of distant spread. Therefore, it would
      really be the primary stage that would set the prognosis rather than the
      consequent treatment, and neither radiation therapy nor RPLND would be true
      independent variables. Similarly, no significant difference is observed when
      patients receive chemotherapy. Cox's regression analysis reveals size of the
      testicular tumor as the only independent predictor of survival. Stage at
      diagnosis does not have an influence by itself and neither does any form of
      therapy. In this sense, the negative effect of radiotherapy is eliminated. We are
      aware that the results drawn from a literature review are far from ideal, but
      there is not enough evidence to suggest an optimal sequence of treatment for this
      rare malignancy. To date, no effective chemotherapy has been found. Whenever the
      tumor is resectable, there appears to be merit in an RPLND.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7571215
TI  - Evaluation of asymptomatic microhematuria.
AB  - OBJECTIVES: The purpose of this study was to evaluate a comprehensive urine
      cytodiagnostic assay to assist in localizing the site of origin and the etiology
      of asymptomatic microhematuria. This analysis, which assesses various qualitative
      and quantitative aspects of the voided urine, is compared simultaneously with
      controls obtained from the established routine urologic evaluation. METHODS: One
      hundred consecutive subjects who presented solely for the evaluation of
      asymptomatic microhematuria were evaluated by the established routine urologic
      evaluation and a refined urine cytodiagnostic assay. For the purpose of this
      study, only calculi and neoplasms were considered significant findings. RESULTS:
      The incidence of significant urologic disease was 13% (3 renal neoplasms, 2
      urothelial bladder carcinomas, and 8 urinary calculi). The refined urine
      cytodiagnostic assay identified both uroepithelial vesical neoplasms, 7 of the 8
      urinary calculi, and none of the 3 renal neoplasms. The presence of dysmorphic
      urinary red blood cells (RBCs) and RBC casts was strongly suggestive of renal
      parenchymal bleeding. Overall, 43 of 44 subjects (98%) with dysmorphic RBCs and
      RBC casts failed to demonstrate any significant urologic etiology. CONCLUSIONS:
      These preliminary results suggest that the refined cytodiagnostic urine assay may
      be helpful in distinguishing whether a given patient's microhematuria is of a
      significant urologic or a renal parenchymal cause. The addition of this
      specialized urinalysis may prove a useful adjunct in improving the diagnostic
      yield in patients with asymptomatic microhematuria.

PMID- 7571214
TI  - Economic modeling to assess the costs of treatment with finasteride, terazosin,
      and transurethral resection of the prostate for men with moderate to severe
      symptoms of benign prostatic hyperplasia.
AB  - OBJECTIVES: We developed a decision analytic model to compare the costs of
      treatment for an initial 2-year period with finasteride, terazosin, and
      transurethral resection of the prostate (TURP) in men with at least moderate
      symptoms of benign prostatic hyperplasia (BPH). Outcome measures were BPH
      treatment costs, duration of symptomatic improvement, and lost productivity days
      (work or other customary activity). METHODS: Patterns of health care resource use
      associated with the treatment of moderate to severe BPH and BPH-related
      complications were evaluated by a survey of urologists and validated by a urology
      consensus panel. BPH safety and efficacy studies in the published literature were
      used to provide probabilities of treatment success. Both a national health care
      resource database (Systemetrics) and Medicare data were used to estimate the
      costs of specific health care services (such as physician services and laboratory
      tests). RESULTS: The probabilities of first-year success (defined as symptomatic
      improvement) for surgery, finasteride, and terazosin were 88%, 67%, and 74%,
      respectively. The most expensive intervention was surgery, followed by
      finasteride and terazosin, at estimated 24-month costs of $6411, $2860, and $2422
      for private insurance and $3874, $2161, and $1820 for Medicare, respectively.
      Duration of symptom improvement was comparable for the three treatments.
      Estimates of usual activity days lost (work or other customary activity) were 22,
      8, and 8 days for surgery, finasteride, and terazosin, respectively. CONCLUSIONS:
      As a primary intervention for patients considering conventional clinical
      approaches to BPH treatment, pharmacotherapy is expected to be less expensive
      than TURP over the initial 2 years of therapy.

PMID- 7571216
TI  - A modification of standard percutaneous nephrolithotripsy technique for the
      morbidly obese patient.
AB  - OBJECTIVES: Urolithiasis in the morbidly obese patient presents several unique
      challenges to the urologist, and its treatment often requires creativity and
      innovation. We present a new modification of standard percutaneous
      nephrolithotripsy (PNL) technique, which is very helpful in overcoming some of
      the problems that are encountered when performing PNL in this group of patients.
      METHODS: We present 5 patients in whom this new technique has been used. Each had
      either failed prior extracorporeal shock-wave lithotripsy (ESWL) therapy or their
      size and abdominal girth precluded use of ESWL technology. All 5 patients
      underwent PNL. The radiographically measured skin-to-stone distances (determined
      by computed tomography or ultrasonography or both) exceeded the lengths of the
      standard percutaneous access sheaths and the 26 F rigid nephroscope. Thus larger
      and longer Amplatz access sheaths and a 30 F gynecologic laparoscope were used to
      reach the stones. Standard ultrasonic lithotripsy was then performed, and
      extralong bronchoscopic grasping forceps were used to remove stone fragments.
      RESULTS: All 5 patients were rendered stone-free using this technique. There was
      no significant perioperative morbidity. CONCLUSIONS: For this very challenging
      group of patients, the use of larger and longer access sheaths and the
      gynecologic laparoscope have been very effective additions to the urologists'
      armamentarium in the treatment of urolithiasis.

PMID- 7571217
TI  - Clinical significance of serum ferritin in patients with renal cell carcinoma.
AB  - OBJECTIVES: We examined the serum ferritin levels in 158 patients with renal cell
      carcinoma and 101 healthy control subjects between 1987 and 1994 to investigate
      the value of this intracellular protein as a tumor marker. METHODS: Preoperative
      and postoperative serum ferritin values were analyzed and the patients were
      stratified to three groups accordingly: group 1, patients with normal values (N
      N); group 2, those with preoperative high and postoperative normal (H-N); and
      group 3, those with preoperative normal or high with postoperative high ferritin
      levels (H-H). RESULTS: The mean serum ferritin level in 101 healthy control
      subjects was 85.7 +/- 63.6 ng/mL (range, 3.7 to 265.2). The upper limit of
      normal, which was calculated by adding 2 standard deviations to the mean was
      219.9 ng/mL. Mean serum ferritin in patients with renal cell carcinoma was 274.2
      +/- 276.3 ng/mL, which was significantly higher than that of control values (P <
      0.01). The sensitivity, specificity, and overall accuracy rate for ferritin
      increase was 94%, 50%, and 61%, respectively. Multivariate analysis showed that
      the aforementioned grouping and stage of the disease were the two independent
      prognostic parameters. Preoperative ferritin levels lost its significance on
      multivariate analysis. CONCLUSIONS: Our study shows that although serum ferritin
      was a useful tool in diagnosing and staging patients, it was not ideal in early
      stages. However serum ferritin seems to be more valuable for follow-up;
      postoperative values, indeed, predict the prognosis.

PMID- 7571218
TI  - Bladder-sparing multimodality treatment of muscle-invasive bladder cancer: a five
      year follow-up.
AB  - OBJECTIVES: To determine the long-term results of a bladder-sparing approach in
      the treatment of muscle-invasive bladder cancer. METHODS: Ninety-four patients
      with invasive transitional cell carcinoma of the bladder were treated by
      transurethral resection followed by 2 or 3 cycles of cisplatin-based
      chemotherapy. Patients were then treated with 6480 cGy of radiation in 49
      patients, segmental cystectomy in 8, or surveillance only in 7. Patients who
      failed to respond to chemotherapy or radiation therapy, or who developed
      recurrent muscle-invasive disease in follow-up, underwent salvage cystectomy.
      Patients were then carefully followed for a median follow-up of more than 5
      years. RESULTS: After initial therapy, 53 patients (56%) were alive with their
      bladder preserved. Thirty of those 53 (57%) developed a local recurrence in
      follow-up. After a median follow-up of more than 5 years, the ultimate relapse
      free survival is 49% (Stage T2, 84%; T3, 53%; and T4, 11%; P < 0.01). Of all
      patients enrolled, 53% had bladder preservation; however, of the currently
      surviving patients, 16 of 39 (41%) have their bladders intact (T2, 50%; T3, 37%;
      T4, 0%). Only 18% of the initially enrolled population is alive with a preserved
      bladder. The 5-year survival of patients who had cystectomy at some point during
      the study, compared with those who have had their bladders preserved, was 65%
      versus 40%, respectively (P < 0.01). CONCLUSIONS: Our long-term results with
      multimodality therapy with attempted bladder preservation showed no definitive
      improvement in survival compared with modern series of cystectomy alone, and a
      disappointingly low rate of disease-free bladder preservation. We found a high
      rate of locally recurrent disease in the preserved bladders. We also noted a
      decrease in survival in our patients with bladder preservation compared with
      those without preservation. Bladder preservation, although possible, should be
      limited to a very select group of patients.

PMID- 7571219
TI  - Analysis of the prevalence of voiding symptoms in Maori, Pacific Island, and
      Caucasian New Zealand men.
AB  - OBJECTIVES: Data from a community-based sample of 515 men were used to assess the
      prevalence and presentation of voiding symptoms in Caucasian, Maori, and Pacific
      Island men in the city of Porirua, New Zealand. METHODS: A random sample,
      stratified by age groups of 10 years, was obtained for men 40 years and older.
      Two hundred men were entered into each 10-year age stratum. Frequency of symptoms
      and quality of life were measured using the International Prostate Symptom Score
      (IPSS) questionnaire. Bothersomeness of symptoms was assessed using questions
      from the American Urological Association symptom bother index. Data were analyzed
      according to age and ethnic group with differences between groups measured by
      analysis of variance. RESULTS: Symptom score was found to increase with
      increasing age of subjects, with men in the 40 to 49 years age group recording a
      mean score (+/- SE) of 2.9 +/- 0.3, increasing to a mean score of 4.8 +/- 0.4 for
      men aged 50 to 59 years, 7.4 +/- 0.9 for men aged 60 to 69 years, and 7.4 +/- 0.9
      for men in the 70 year and older age group. Significant symptoms, represented by
      a symptom score of 8 or greater, were found in 12.9% of men aged 40 to 49 years,
      22.3% of men aged 50 to 59 years, 33.7% of men aged 60 to 69 years, and 33.3% in
      the 70 year and older age group. No difference was demonstrated in the prevalence
      of symptoms between Caucasian, Maori, and Pacific Island men. CONCLUSIONS:
      Despite having a similar prevalence of voiding symptoms to Caucasian men, few
      Maori or Pacific Island men seek help for their urinary symptoms. The level of
      understanding of the underlying disease process is poor for men of all ethnic
      backgrounds and emphasizes the important need for greater public awareness and
      education with respect to prostate disease.

PMID- 7571221
TI  - Electrosurgical vaporization of the prostate in the canine model.
AB  - OBJECTIVES: To investigate the histopathologic changes and heating patterns
      caused by electrosurgical vaporization of the prostate in the living canine
      model. METHODS: Prostate electrosurgical vaporization was undertaken in the
      canine model. Temperatures within and near the prostate and of the irrigation
      fluid were measured during a single pass and during the creation of a vaporized
      cavity. The prostate and adjacent tissues were examined by gross and microscopic
      pathology. RESULTS: Coagulation occurred deep to the vaporization zone for 1.38
      to 1.44 mm for a single pass of the rolling cylinder and up to 2.52 mm for
      multiple passes. Thermometry revealed temperature increases of only 4 degrees C 5
      mm away from the vaporization site. The largest temperature increases were found
      in the irrigation fluid as it passed through the prostatic fossa. Microscopic
      pathology revealed no damage to adjacent tissues. CONCLUSIONS: Electrosurgical
      vaporization creates minimal deep heating and coagulation beyond the vaporized
      cavity. The majority of the heat is removed by the irrigation fluid.

PMID- 7571220
TI  - Doxazosin in physiologically and pharmacologically normotensive men with benign
      prostatic hyperplasia.
AB  - OBJECTIVES: To compare the effects of doxazosin on blood pressure when used for
      the treatment of benign prostatic hyperplasia (BPH) in men who are either
      physiologically or pharmacologically normotensive. METHODS: Sixty-three men with
      BPH were enrolled in two open-label, parallel, randomized studies. Thirty-one
      were physiologically normotensive and 32 had hypertension controlled by
      antihypertensive therapy (pharmacologically normotensive). Of these, 17 were
      taking calcium channel blockers; 6, angiotensin-converting enzyme inhibitors; and
      9, beta blockers. After a 3-week titration period, patients from one study
      received doxazosin (4 mg/day) for 3 months, given as a single dose in either the
      morning or evening, and in the second study patients were randomized to receive
      either 4 mg or 8 mg daily, either in the morning or evening. Effects on blood
      pressure, maximum uroflow, and the Boyarsky symptom score were measured. RESULTS:
      Doxazosin produced statistically significant but clinically unimportant
      reductions in blood pressure in both physiologically and pharmacologically
      normotensive groups. Statistically and clinically significant improvements in BPH
      symptoms and maximal perfusion occurred in both groups within 1 month, and
      further improvements were improved after 3 months. These effects were evident
      whether doxazosin was administered in the morning or evening. Doxazosin was well
      tolerated, the only adverse events being dizziness in 5 patients and fatigue in
      4. By protocol, all patients reporting adverse events were required to be
      discontinued from the study. Adverse events did not differ between the groups.
      There was some indication that patients experiencing adverse events also
      experienced greater reductions in blood pressure. CONCLUSIONS: Doxazosin may be
      introduced for the treatment of BPH in hypertensive men whose blood pressure is
      already controlled by another antihypertensive agent, without a further clinical
      reduction in blood pressure. It is effective and well tolerated as a once-daily
      dose given in the morning or evening.

PMID- 7571222
TI  - An analytical comparison of the three most commonly used prostate-specific
      antigen assays: Tandem-R, Tandem-E, and IMx.
AB  - OBJECTIVES: To compare the similarity of individual prostate-specific antigen
      (PSA) results when using the Tandem-R PSA assay, the Tandem-E PSA assay, or the
      IMx PSA assay; to assess the lot-to-lot variation within (intra-assay interlot)
      and between (interassay interlot) the Tandem-R, Tandem-E, and IMx PSA assays; and
      to evaluate the individual and overall potential lot-to-lot bias of the Tandem-R,
      Tandem-E, and IMx PSA assays. METHODS: Forty-nine serum samples (PSA values from
      0 to 85 ng/mL) were each tested by three separate lots (manufacturer's reagent
      materials) of Tandem-R, Tandem-E, and IMx PSA assays. Therefore, a total of nine
      different lots were utilized per patient sample in this investigation. Analyses
      primarily focused on three ranges: 0 to 10 ng/mL (low), 10 to 85 ng/mL (high),
      and 0 to 85 ng/mL (overall). RESULTS: In the 0 to 10 ng/mL range, 93% of the
      assay comparisons yielded an actual difference of less than 1 ng/mL. All three
      assays demonstrated excellent correlation within and between their three
      respective lots, within all three ranges. The 95% confidence intervals around the
      percent coefficient of variation (CV) demonstrated similar results for each assay
      (CV range, 3.2% to 6.0%). All lots demonstrated an average actual PSA bias of
      less than +/- 1 ng/mL. The average percent PSA bias was also similar between all
      three assay systems. All lots demonstrated a less than +/- 4% bias. CONCLUSIONS:
      Overall, the Tandem-R and IMx PSA assays yielded slightly lower results than the
      Tandem-E PSA assay. However, these differences were not statistically
      significant. In addition, the overall lot-to-lot variation (intra-assay and
      interassay) was not statistically significant, and the actual or percent PSA bias
      was minimal with these three assays. Therefore, a clinician can feel confident
      that a patient's serum sample should yield a similar and interchangeable result,
      whether it is determined by the Tandem-R, Tandem-E, or IMx PSA assay system.

PMID- 7571223
TI  - Detection of latent prostate cancer from routine screening: comparison with
      breast cancer screening.
AB  - OBJECTIVES: One criticism of routine prostate cancer screening is the possibility
      that latent prostate cancer would be detected and treated in men who would
      otherwise never need treatment for their prostate cancer. This increase in latent
      cancer detection with screening could lead to overtreatment, with its resulting
      increases in morbidity, mortality, and health care costs. In contrast, breast
      cancer screening is widely accepted, and there is little concern about latent
      breast cancer detection and overtreatment of breast cancer due to screening. This
      study compares the detection of latent prostate cancer from screening with the
      detection of latent cancer in an established cancer screening program (breast
      cancer screening) and examines the risk that screening leads to an increase in
      detection of latent cancer over traditional methods of detection for both breast
      and prostate cancer. METHODS: The present study reviews outcomes data from
      several large prostate and breast cancer screening trials. The natural history of
      latent prostate and breast cancer is then reviewed. By applying this information,
      the rate of latent prostate cancer detection and latent breast cancer detection
      with screening is compared. RESULTS: Recent large-scale prostate cancer screening
      studies have reported a latent cancer detection rate of 2.9% to 8.0%. This rate
      of detection is virtually the same as that found by traditional methods of
      detection. Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer that
      accounts for 16.2% to 23.7% of breast cancers detected in screening programs
      using mammography. The literature estimates that DCIS will remain latent in 50%
      to 66% of patients. These data suggest that the latent breast cancer detection
      rate in screening programs is 8.1% to 15.6%, which is a threefold to fivefold
      increase compared with the detection rate of latent breast cancer prior to
      screening with mammography. CONCLUSIONS: These results suggest that the latent
      prostate cancer detection rate from screening is similar to or less than the
      latent breast cancer detection rate from screening. Furthermore, prostate cancer
      screening does not appear to increase the detection rate of latent cancer over
      traditional methods of detection. This should eliminate concern that prostate
      cancer screening will lead to overtreatment of prostate cancer.

PMID- 7571224
TI  - Prostate cancer staging after radiation utilizing laparoscopic pelvic
      lymphadenectomy.
AB  - OBJECTIVES: This report assesses the feasibility of laparoscopic pelvic
      lymphadenectomy in irradiated patients with prostate cancer being considered for
      salvage therapy. METHODS: Six men, each with a prior history of external beam
      radiation therapy, and prostate-specific antigen or clinical failure, were
      selected as potential candidates for salvage therapy. Utilizing a standard
      diamond pattern trocar conformation, laparoscopy was performed to evaluate pelvic
      lymph node status. RESULTS: The procedure was successfully completed in all
      patients with a mean operating room time of 154 minutes. Blood loss averaged 55
      cc. Serious intraoperative or postoperative complications were not encountered in
      the follow-up of 6 months. Metastatic disease was demonstrated in 1 patient.
      CONCLUSIONS: Laparoscopic pelvic lymph node dissection is technically feasible in
      patients who have received irradiation, and appears to confer no additional
      morbidity over standard laparoscopic lymphadenectomy.

PMID- 7571225
TI  - Cell saver and radical retropubic prostatectomy: analysis of cost-effectiveness.
AB  - OBJECTIVES: To determine the effectiveness of using cell saver suction during
      radical prostatectomy to decrease the risk of random donor transfusions in
      patients predonating blood, as well as to compare costs. METHODS: From March 1992
      to October 1993, two consecutive groups of 86 patients underwent radical
      retropubic prostatectomy. The first group utilized predonated blood alone, and
      the second group utilized cell saver suction and predonated blood. The two groups
      were compared with respect to their transfusion records, preoperative and
      discharge hemoglobins, and estimated blood losses to determine the usefulness of
      cell saver suction during radical retropubic prostatectomy. RESULTS: There was no
      statistical difference in the rate of random donor blood transfusions between
      these two evenly matched groups of patients. The risk of receiving random donor
      transfusions was decreased to 5% by having 4 U of blood predonated by or for the
      patient prior to radical prostatectomy. CONCLUSIONS: For patients who are able to
      predonate blood, cell saver suction is neither cost-effective nor useful in
      decreasing the risk of receiving random donor blood transfusions.

PMID- 7571226
TI  - Defective mitochondrial oxidative phosphorylation in varicocele-bearing
      testicles.
AB  - OBJECTIVES: Our previous study revealed a decreased blood flow in varicocele
      bearing testicles. For further understanding of the possible mechanism of
      varicocele-induced infertility, we investigated the changes in energy metabolism
      in varicocele-bearing testicles. METHODS: Partial ligation of the left renal vein
      was performed in 40 Wistar rats to induce dilation of the internal spermatic
      vein, and sham operations were performed in 20 other age-matched Wistar rats
      serving as controls. Orchiectomy was done at 1, 2, 4, and 6 months after
      induction of varicocele (or sham operation) in both groups. The histologic
      changes in the testicles were evaluated under the light microscope. The
      concentration of adenine nucleotides was determined by high-performance liquid
      chromatography, and various enzyme activities of mitochondria were determined by
      a spectrophotometer. RESULTS: Histologic studies of varicocele-bearing testicles
      showed a lower Johnsen score (8.5 +/- 0.7 versus 9.3 +/- 0.5) and a decreased
      mean testicular tubular diameter (280.0 +/- 3.2 versus 295.0 +/- 1.4 microns)
      compared with the testicles in the sham-operated group. The energy charge
      decreased from 0.71 +/- 0.04, 0.70 +/- 0.03, 0.69 +/- 0.06, and 0.64 +/- 0.03 to
      0.62 +/- 0.08, 0.59 +/- 0.05, 0.58 +/- 0.05, and 0.56 +/- 0.02 at 1, 2, 4, and 6
      months, respectively. The reduced nicotinamide-adenine dinucleotide-cytochrome c
      reductase activities were decreased from 136.6 +/- 4.9, 127.3 +/- 10.7, 121.6 +/-
      7.8, and 118.9 +/- 8.5 to 96.3 +/- 13.9, 95.6 +/- 27.8, 88.3 +/- 13.8, and 80.4
      +/- 8.7 nmol/min/mg of protein, respectively; the succinate-cytochrome c
      reductase activities were decreased from 50.4 +/- 2.7, 49.0 +/- 4.7, 49.6 +/-
      7.1, and 42.6 +/- 1.6 to 40.3 +/- 7.3, 41.0 +/- 11.5, 40.2 +/- 5.7, and 32.0 +/-
      1.3 nmol/min/mg of protein, respectively; and the cytochrome c oxidase activities
      were decreased from 361.2 +/- 23.4, 350.3 +/- 25.5, 223.5 +/- 12.9, and 194.1 +/-
      18.3 to 253.7 +/- 32.9, 256.4 +/- 38.8, 178.2 +/- 15.7, and 147.1 +/- 17.2
      nmol/min/mg of protein at 1, 2, 4, and 6 months, respectively. CONCLUSIONS: We
      thus suggest that defective energy metabolism plays an important role in the
      impairment of spermatogenesis of varicocele-bearing testicles.

PMID- 7571227
TI  - Extracorporeal shock-wave lithotripsy in children.
AB  - OBJECTIVES: To analyze the efficacy and complication rates of extracorporeal
      shock-wave lithotripsy in children. METHODS: Between 1987 and 1994, 8760 patients
      with urinary calculi were treated at our institution. A total of 70 (0.8%)
      children 3 to 14 years old underwent lithotripsy using the Siemens Lithostar or
      the Lithostar Plus. A total of 100 calculi in 74 urinary tracts were treated,
      requiring 129 extracorporeal shock-wave lithotripsy sessions. There were 47
      caliceal stones, 31 in the renal pelvis, 16 in the ureter, and 6 staghorn stones.
      The Lithostar Plus was used in 8 patients, for 3 caliceal, 3 pelvic, and 2
      staghorn stones. Follow-up consisted of nephrotomogram or ultrasound 1 day and 1
      to 3 months postoperatively. RESULTS: Complete removal of all stone fragments was
      achieved in 98.5% of the patients after 3 months. Re-treatment was necessary in
      20 patients (29.4%). All patients were treated as outpatients, 51 (72.9%) with
      intravenous sedation and 19 (27.1%) without anesthesia. Complications were
      present in 7 patients (10%) who had colic and received medical treatment, and
      convalescence was uneventful. CONCLUSIONS: Extracorporeal shock-wave lithotripsy
      using the Lithostar and the Lithostar Plus has been demonstrated to be an
      effective noninvasive procedure to treat radiopaque and even radiolucent or
      slightly opaque urinary calculi in children.

PMID- 7571228
TI  - Flutamide-induced cryptorchidism in the rat is associated with altered
      gubernacular morphology.
AB  - OBJECTIVES: One of the major controversies regarding descent of the testes is
      whether androgenic regulation of the gubernaculum testes exists. To determine if
      antiandrogens can alter the development of the gubernaculum within the fetus, the
      following experiment was performed. METHODS: Timed pregnant Sprague-Dawley rats
      were treated with either flutamide, dihydrotestosterone (DHT), or vehicle alone
      (controls) from gestational day (GD) 15 to 17. Fetal specimens were removed via
      cesarean section on GD 18 and 20. Serial coronal sections were obtained, and
      digital microscopy with computer-assisted reconstruction was used to ascertain
      the morphology of the three components of the gubernaculum, that is, the
      gubernacular cord and the mesenchymal and muscular components of the gubernacular
      bulb. RESULTS: Flutamide significantly prevented and DHT significantly enhanced
      gubernacular cord regression compared with controls (P < 0.01). Flutamide also
      resulted in a significant inhibition of the gubernacular bulb outgrowth, with
      diminution of both the mesenchymal and muscular components of the gubernacular
      bulb. CONCLUSIONS: These data suggest that androgens play an active role in
      gubernacular cord regression and gubernacular outgrowth within the fetal rodent.

PMID- 7571229
TI  - Diagnostic tunica vaginoscopy in a rodent model of testicular torsion.
AB  - OBJECTIVES: To evaluate the effectiveness of percutaneous endoscopy of the tunica
      vaginalis for identifying testicular torsion in a rodent model. METHODS: One
      testis was randomly selected in 10 Wistar rats weighing 500 to 600 g. Following 2
      hours of 720 degree torsion, bilateral percutaneous endoscopy of the tunica
      vaginalis was performed by a blinded investigator utilizing a 70 degree
      cystoscope lens through a single midline 3 to 4 mm scrotal cutdown incision.
      RESULTS: Using this technique, the blinded investigator was able to identify the
      torsed testis rapidly in every case, which was distinguished by its cyanotic
      color and by the size and color of the testicular surface vessels. CONCLUSIONS:
      Tunica vaginoscopy is a simple, accurate, rapidly performed, minimally invasive,
      diagnostic technique in this experimental model of testicular torsion.

PMID- 7571230
TI  - An original balloon-expanding urethral suture guide for radical prostatectomy.
AB  - Between August 1991 and July 1994, an original balloon-expanding urethral suture
      guide (24 F) was used in 157 consecutive cases of radical retropubic
      prostatectomy. Both the instrument and its clinical use are described. This guide
      guarantees good intraoperative exposure of the sectioned urethral stump during
      vesical reanastomosis, thus improving the technical feasibility of radical
      prostatectomy.

PMID- 7571231
TI  - Laparoscopic bladder augmentation using stomach.
AB  - We present a case of bladder augmentation with stomach, via a laparoscopic
      approach. The patient was a 17-year-old girl with sacral agenesis and a poorly
      compliant bladder. A wedge of stomach, based on the right gastroepiploic pedicle,
      was obtained using a stapled technique. The bladder was opened and the gastric
      segment was sutured in place. A needle suspension was also carried out. Three
      months later, the patient was dry and catheterizing every 4 hours. Laparoscopic
      bladder augmentation is technically feasible and, in the properly selected
      patient, may be the preferred technique for creation of a compliant high-volume
      urinary reservoir.

PMID- 7571232
TI  - Invasive bladder cancer following cardiac transplantation.
AB  - Iatrogenic immunosuppression following renal transplantation has been associated
      with the development and progression of multiple neoplasms, including
      transitional cell carcinoma (TCC). We present the first report of invasive TCC of
      the bladder managed with radical cystectomy in a cardiac transplant recipient.
      The short survival of this patient, despite organ-confined disease at the time of
      cystectomy, illustrates the necessity of early diagnosis and aggressive treatment
      of malignancy following organ transplantation.

PMID- 7571233
TI  - Staphylococcus periprostatic abscess: an unusual cause of acute urinary
      retention.
AB  - Prostatic abscess has occasionally been known to present with urinary retention.
      We report an unusual case of a Staphylococcus aureus periprostatic abscess
      causing acute urinary retention. Diagnosis was made by transrectal sonogram and
      computed tomography scan, and the patient was treated successfully with
      intravenous antibiotics, perineal exploration, and drainage.

PMID- 7571234
TI  - Femoral neuropathy after pelvic surgery.
AB  - Femoral neuropathy is an uncommon complication following pelvic surgery. We
      report on 2 cases of femoral nerve injury after pelvic surgery: 1 patient
      received radical cystectomy due to invasive transitional cell carcinoma of the
      urinary bladder, and the other patient had a transurethral resection of the
      bladder and received exploration and biopsy of a tumor mass over the right
      sacroiliac joint area. Pathogenesis and prevention of the complication of femoral
      neuropathy are discussed in the following report.

PMID- 7571235
TI  - Immediate impotence after penetrating perineal trauma: restoration of erections
      with penile artery revascularization, corpus cavernosum aneurysm repair, and deep
      penile venous ligation.
AB  - Erectile dysfunction can result from blunt or penetrating pelvic or perineal
      trauma. Rupture of the corpora cavernosa leading to loss of the veno-occlusive
      mechanism and penile artery occlusion have been found in these patients. We
      present a case of immediate loss of erectile function after penetrating perineal
      trauma resulting in corpus cavernosum rupture and traumatic occlusion of multiple
      arteries in the hypogastric-cavernous bed. Conservative management of the corpus
      injury resulted in post-traumatic aneurysmal dilation at the site of injury with
      venous leakage from aberrant veins. Penile arterial revascularization and
      aneurysm repair with deep penile venous ligation resulted in near-complete return
      of normal erectile function.

PMID- 7571236
TI  - Magnetic resonance imaging of vascular lesions of the scrotum and penis.
AB  - We report 2 rare cases of vascular lesions in the scrotum and penis: an
      arteriovenous malformation in a young man and a lymphohemangioma in a boy. Both
      patients had undergone previous treatment and had recurrent lesions. Magnetic
      resonance imaging was performed preoperatively for detailed information regarding
      lesion extent and involvement of adjacent structures.

PMID- 7571237
TI  - Increased prostatic blood flow in response to microwave thermal treatment:
      preliminary findings in two patients with benign prostatic hyperplasia.
AB  - OBJECTIVES: To determine the effects on prostate blood flow of heat generated by
      microwave thermal treatment in patients with benign prostatic hyperplasia.
      METHODS: Prostate blood flow was evaluated by continuous transrectal color
      Doppler ultrasonography in 2 patients at baseline, after implantation of
      interstitial needles used for thermal mapping, and during microwave thermal
      treatment. Temperatures at 30 prostatic, periprostatic, urethral, and rectal
      sites were continuously monitored. In 1 patient, transrectal prostate compression
      was applied and the blood flow and temperature response to this maneuver noted.
      RESULTS: Microwave thermal treatment achieved maximum prostate temperatures of 59
      degrees C at 5 mm radially from the urethra. Urethral and rectal temperatures
      remained low. Marked increases occurred in prostate blood flow in response to
      microwave thermal treatment. These increases were apparent throughout the
      prostate gland, with the greatest increase in perfusion occurring in the
      peripheral zone and the posterior half of the transitional zone. After 15 minutes
      of microwave treatment, peak systolic blood flow increased 99% and 70% in
      patients 1 and 2, respectively, while end-diastolic blood flow climbed 50% and
      112%, respectively. Prostate compression resulted in a prompt quenching of blood
      flow and an increase in prostate temperature. CONCLUSIONS: Based on these
      preliminary findings in 2 patients, prostate blood flow increases markedly in
      response to microwave thermal treatment. This compensatory increase in blood flow
      is likely to be a significant treatment-limiting factor in achieving effective
      thermoablation.

PMID- 7571238
TI  - Infertility due to antisperm antibodies.
AB  - Immunoinfertility is an important problem, involving a significant number of
      infertile couples. Although the presence of antibodies on sperm has better
      prognostic value than those in serum or seminal plasma, it may not be the sole
      authentic evidence of immunoinfertility. Infertility from antisperm antibodies is
      likely only when they bind to a relevant sperm antigen involved in a specific
      fertility function. The variance in functional deficits seen in immunologic
      infertility is most likely related to antibodies directed at different sperm
      antigens or different class, subclass, or isotypes. Antibodies to FA-1 seem to be
      of significant importance in human immunoinfertility. In approaching couples with
      infertility, a high index of suspicion for antibodies is necessary to avoid
      misdiagnosis. In the optimal situation, all semen analyses should be screened for
      sperm-bound antibodies, but if this is impractical, testing should be performed
      on high-risk individuals (Table I). In couples in which the man has sperm-bound
      antibodies, and in whom there is no identifiable female factor, treatment should
      be instituted. Most treatments for immunoinfertility have been disappointing
      because of poor results, adverse effects, or high cost. Corticosteroid therapy
      has shown some promise in published reports (mostly poorly designed studies), but
      increase in pregnancy rate is modest and adverse effects may be significant. In
      our opinion, informed consent should be documented prior to institution of
      corticosteroid therapy, and subjects should be closely monitored. Advanced
      reproductive technologies offer a higher safety profile, and, with increasing
      technology, higher pregnancy rates. We recommend progressing from "low-tech"
      procedures, such as IUI and reserving the higher level procedures, such as IVF
      and ICSI, for those couples in whom pregnancy does not occur. The highest level
      reproductive technologies give the best current prospects for pregnancy in
      patients with this difficult problem but also are invasive and costly. It is
      hoped that further work in the laboratory will give rise to newer, safer, and
      less expensive effective treatments in the very near future.

PMID- 7571239
TI  - Combination of laser irradiation and transurethral resection of the prostate.

PMID- 7571240
TI  - Prostate needle biopsy following radiotherapy for prostate cancer.

PMID- 7571241
TI  - Prostate size and transurethral laser evaporation of the prostate.

PMID- 7571242
TI  - [Metabolic profile in cows in the peripartum period with and without retained
      placenta].
AB  - Blood samples were taken and subjected to biochemical analysis in the crossbred
      cows of the Red-Pied, Black-Pied or Holstein-Friesian breed raised on a large
      farm under standard conditions, with the average annual milk yield of 4,300 kg
      milk, and divided into two groups--cows with afterbirth retention and without it;
      the samples were taken in the last period of pregnancy (since day 245), during
      parturition, and within the first 50 days post partum. In both groups, the values
      of acid-base balance and metabolic profile mostly ranged within the interval of
      reference values, nevertheless there were certain trends and differences in
      absolute values as well as in the dynamics of changes, but they did not always
      show a doubtless character and the same significance. The cows with afterbirth
      retention exhibited a trend of a more expressive decrease in partial pressure
      CO2, actual acid output and phosphorus level. Glucose level at the end of
      pregnancy was statistically significantly lower (P < 0.01), cholesterol level
      also decreased (P < 0.05). On the other hand, the cows with afterbirth retention
      had, at the end of pregnancy, statistically significantly higher concentrations
      of urea and creatinine (P < 0.05-0.01), a higher bilirubin level and enzyme
      activities of acid phosphatase, and particularly of aspartate aminotransferase
      and lactate dehydrogenase (P < 0.05-0.01). There were insignificant differences
      in the concentrations of total protein, calcium, magnesium and enzyme activity of
      alkaline phosphatase and gammaglutamyl transferase.

PMID- 7571245
TI  - [The NEFERM test in the identification of psychrotrophic bacteria isolated from
      milk and dairy products].
AB  - Sanitary and nutriti on quality of foods from animal sources, that means also of
      milk and dairy products, are significantly influenced by the presence of
      psychrotrophic bacteria, the lipolytic and proteolytic activity of which
      contributes to their nutritive and sensory changes. This applies particularly to
      psychrotrophic bacteria of the genus Pseudomonas, Shewanella, Alcaligenes and
      Flavobacterium (Muir and Phillips, 1984; Piton and Richard, 1985; Craven and
      Macauley, 1990). These bacteria cause raw and pasteurized milk to turn bitter and
      gelatinize, and/or technological problems during processing. In the present paper
      the possible use of NEFERM-test and numerical identification system TNW was
      verified for identification psychrotrophic, nonfermentative bacteria isolated
      from milk and dairy products. This research is a continuation of our preceding
      work (Urbanova and Pacova, 1995) dealing with identification of these bacteria in
      poultry. The test comprised 35 psychrotrophic, gram-negative, oxidase-positive
      nonfermentative bacteria isolated from raw milk (30 strains) and hard cheeses (5
      strains). A commercial diagnostic kit NEFERM-test (Lachema a.s., Brno) and
      respective conventional methods were parallelly used for identification: the
      conventional methods were complemented by assays of oxidase (OXI) and beta
      galactosidase (ONPG) using of commercial strips Lachema a.s. Additional tests
      were as follows: gelatin and Tween 80 hydrolysis, fluorescein production. The
      readings of yellow or orange pigment production were also applied. A numerical
      identification system TNW was used to process the results (Czech Collection of
      Microorganisms, Faculty of Science, Masaryk University, Brno). Correct
      identification of bacteria by means of commercial diagnostic kits depends
      particularly upon the high goodness of fit of the results obtained by
      conventional tests in relation to those obtained by commercial kits.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571244
TI  - [Results of surgical treatment in disorders of the thoracolumbar disks in dogs].
AB  - The clinical records of 90 dogs with thoracolumbar disc disease treated by
      fenestration or decompressive surgery on Surgical Department of the University of
      Veterinary and Pharmaceutical Sciences in Brno between September 1992 and March
      1994 were reviewed. The breed, age and sex predisposition, rate of disc
      protrusion or extrusion and number of multiple disc extrusions were recorded. The
      frequency of disc protrusion/extrusion at each intervertebral space in
      thoracolumbar region of spine was also observed. Dogs were grouped by clinical
      signs of disease in four groups. Recovery rates depending on the pre-operative
      neurological grade of spinal injury and duration of clinical signs were compared.
      Patients were observed at least 6 months after surgery and the results of therapy
      were classified as good (complete recovery of motor and urinary function), fair
      (some remaining dysfunction, either motor or urinary, but animal retained
      independent function and usefulness) and poor (not enough improvement to be
      returned to the owner as an independent animal). Eight breeds and mixed-breed
      dogs were represented in the 90 cases of thoracolumbar disc disease. Shorthaired
      Dachshunds predominated (58.9%). The age range of dogs was 3-12 years; 52% were
      males and 48% females. Incidence of disc protrusion was 13.3% and disc extrusion
      86.6% of the cases, with the frequency 3.3% of multiple disc extrusions. The most
      common site of lesion was the T12-T13 interspace. Twelve dogs in group II were
      treated by fenestration with good results of therapy in all cases. There was no
      recurrence of clinical signs during period of observation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7571246
TI  - [Staphylococcus aureus in bulk milk samples].
AB  - In the years 1993-1994 the occurrence of Staphylococcus aureus was investigated
      in bulk milk samples in the area where a Baby Food Factory at Zabreh in Moravia
      is located, and in Bruntal, Zlin and Policka districts. Evaluation of the results
      was based on ECC Directive 92/46, while the dynamics of S. aureus presence was
      followed for the whole period of observation as well as in the particular
      seasons. A total of 4,485 samples was processed. Out of these, 50.7% contained
      less than 100 CFU/ml of S. aureus, 41.4% contained 100-500 CFU/ml, 6.73% 500
      2,000 CFU/ml and 1.14% contained more than 2,000 CFU/ml (Fig. 1). The samples
      were divided into three categories: private new-established farms, cooperative
      and State-owned enterprises in the area of the Zabeh Factory and others (Zlin,
      Bruntal and Policka districts). There were highly significant differences in the
      content of staphylococci (P = 0.01%) between the three categories of samples.
      Ninety-eight percent of samples from private farms, 96% samples from the Zabreh
      Factory area and 85% of the other samples comply with the regulation EEC 92/64
      (Tab. I) for raw cow's milk for the manufacture of products "made with raw milk"
      whose manufacturing process does not involve any heat treatment (Fig. 2). The
      occurrence of S. aureus in the Zabreh Factory area shows an expressive seasonal
      dynamics (P = 0.005%) with maximum values in winter months (December-March) and
      minimum values in summer months (July-October)-Fig. 3. The same relationship can
      be seen on more extensive data files for the particular producers (Fig.
      4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571243
TI  - [Effectiveness of moxidectin (Cydectin inj.) in mixed Psoroptes ovis and
      Sarcoptes ovis infestations in sheep].
AB  - Field efficacy of moxidectin injectable was evaluated in sheep naturally infected
      with both Psoroptes ovis and Sarcoptes ovis mange. Three groups of fifteen ewes
      were selected from the flock based on parasitological and clinical status. Group
      1 remained as untreated controls. Group 2 animals received a subcutaneous
      injection of moxidectin at 0.2 mg/kg body weight on Day 0; Group 3 animals
      received 0.2 mg/kg moxidectin twice on Day 0 and Day 7. Efficacy was assessed by
      taking skin scrapings from each animal on Days -4, 0, 7, 14, 28 and 35 post
      treatment (P.T.) and counting viable mite stages and species. In both treated
      groups the signs of itching disappeared within seven days P.T. Rapid clinical
      improvement was associated with reduction in numbers of mites compared with
      initial score which was over 90%. However, in skin scrapings on Day 7 P.T.
      several live mites of both species were present. The second injection of
      moxidectin removed all living mites and skin scrapings from group 3 animals that
      were negative for all mites on days 14, 28 and 35. The weight gain on average in
      group 2 was 2.0 kg and in group 3 2.7 kg, during the 35 days of trial. Untreated
      control animals have lost on average 3.1 kg from the weight at start of trial.
      All untreated animals remained positive and suffered from intensive scratching,
      anorexia and moist active skin lesions. Therefore they were given an emergency
      moxidectin treatment on days 35 and 37 each animal receiving 0.2 mg/kg b.w.,
      subcutaneously. Moxidectin in both tested doses was well tolerated and no local
      reaction on injection sites was observed.

PMID- 7571247
TI  - [The dot-blot technic for quantitative determination of wheat protein in
      sausage].
AB  - A simple immunological method is described by which it is possible to detect the
      wheat flour according to wheat protein in the heat-processed meat products. The
      wheat proteins were extracted with a buffer TRIS-NaCl (0.02 mol/l, 0.5 mol/l)
      from: a) wheat flour; b) model meat products with addition of wheat flour (3.2,
      3.2, 3.6, 0.8, 0.4 and 0.2%); c) commercial meat products containing wheat flour
      (sausages-S, P, PF). The aliquots of the extracts were subjected to an
      immunological dot-blot test. The extracts from the wheat flour and the model meat
      products were used for calibration of this method. The quantitative evaluation of
      the test was based on the spectrophotometric determination of the quantity of the
      violet stain on the nitrocellulose (NC) strip surfaces. The strips were immersed
      into the acetone and the absorbance were determined at 580 nm. The screening of
      the samples by dot-blot procedure proved to be an efficient way of the wheat
      flour determination in the cooked meat products at 0.2% level (i.e. 0.375 ng of
      wheat protein applied to the NC strip). Since the wheat antibody (primary
      antiserum) has no crossreactivity with pork or beef, this technique can be used
      for the detection of plant proteins in the mentioned mixtures.

PMID- 7571248
TI  - [Survival of microscopic filamentous fungi under various temperature conditions].
AB  - Time required for devitalization of Mucor fragillis, Fusarium moniliforme,
      Penicillium glabrum and Aspergillus niger germs at temperatures of 22, 37, 60
      degrees C was determined under laboratory conditions. All of the tested strains
      withstood the temperature 22 degrees C during the period of 42 days in Sabouraud
      agar. At the temperature of 37 degrees C devitalization appeared in the following
      order: F. moniliforme 14 days, P. glabrum 21 days, M. fragillis 28 days, A. niger
      35 days. Temperature of 60 degrees C devitalized all tested strains of
      micromycetes within 5 hours. F. moniliforme appeared to be the most susceptible
      among 4 tested strains while M. fragillis was the less susceptible.

PMID- 7571249
TI  - Application of an equine herpesvirus 1 (EHV1) type-specific ELISA to the
      management of an outbreak of EHV1 abortion.
AB  - Sera from 33 Australian thoroughbred mares were tested during an outbreak of
      equine herpesvirus 1 (EHV1) abortion with an enzyme-linked immunosorbant assay
      (ELISA) for the presence of EHV1-specific antibodies. The ELISA used a
      recombinant EHV1 antigen derived from glycoprotein G (gG) and distinguished
      antibodies to EHV1 from those of the antigenically related and widespread
      herpesvirus EHV4. Sera were obtained from most of the mares on three occasions,
      three, 13 and 67 days after the first abortion. Mares which were negative in the
      ELISA were kept separate from mares which were positive. A second abortion
      occurred two days after the first and two more abortions and one perinatal death
      occurred later. Sera from these last three mares showed a significant increase in
      EHV1-specific antibody on day 13 indicating a recent infection with EHV1. Ten
      other mares did not have antibodies to EHV1 on day 13 but had seroconverted to
      EHV1 by day 67. Despite the EHV1 infection, these mares foaled normally, possibly
      because the infection had occurred either late in gestation or after foaling.
      Seven mares that remained negative in the ELISA throughout the testing period did
      not abort, and neither did 11 mares that were positive in the ELISA when they
      were first tested.

PMID- 7571251
TI  - Seasonal activity of ixodid ticks on goats in northern Greece.
AB  - Ixodid ticks were collected at monthly intervals for 20 consecutive months from
      25 goats of the local breed selected at random from a flock grazing permanently
      around a village in northern Greece. Three species of ixodid ticks were
      recovered, Ixodes gibbosus, Rhipicephalus bursa and Dermacentor marginatus. I
      gibbosus was the most abundant and prevalent species. It was found on the animals
      from October to April, and its activity increased with lower mean temperatures
      and higher relative humidities. R bursa was present from May to August, and its
      activity increased with higher mean temperatures and lower relative humidities. D
      marginatus was present in very small numbers from January to March, with no
      significant correlation with climatic factors.

PMID- 7571250
TI  - Handling of sheep at markets and the incidence of bruising.
AB  - Most sheep sent for slaughter in the United Kingdom are sold through livestock
      markets. This study counted the potentially bruising events at two markets
      handling 12,119 sheep in 549 groups and recorded the bruises on carcases of sheep
      from these markets. There were 1324 and 744 potentially bruising events per 1000
      sheep at markets A and B, respectively. The unloading of 1501 sheep in 40 groups
      and the pre-slaughter handling of 1085 sheep in 60 groups were observed at the
      commercial slaughterhouse where the bruises were recorded. The number of
      potentially bruising events at the slaughterhouse was 694 per 1000 sheep. The
      bruising on the carcases of 58 groups of sheep from market A and 29 groups from
      market B, and of 30 groups of sheep sent to slaughter direct from farms was
      assessed. The sheep from market A had 581 bruises per 1000 sheep, those from
      market B had 377 per 1000 sheep, and the sheep sent direct from farms had 399
      bruises per 1000 sheep. There were some differences in the distribution of the
      bruises on the carcases from the three sources, but no significant differences
      between the total numbers of bruises.

PMID- 7571252
TI  - Growth and oesophagogastric lesions in finishing pigs offered pelleted feed ad
      libitum.
AB  - The growth rates of 458 finishing pigs between 25 kg and 107 kg liveweight, which
      were offered finely ground pelleted feed ad libitum, were determined and their
      stomachs were examined at slaughter. Two herds were involved and a macroscopical
      examination of the mucosal lesions in the pars oesophagea revealed a prevalence
      of 75 per cent of the 274 pigs in herd A and 89 per cent of the 184 pigs in herd
      B with hyperkeratosis of the pars oesophagea, and approximately 11 per cent of
      the pigs in both herds with extensive erosions and/or ulceration; on average the
      pigs with extensive lesions gained 50 to 75 g/day less weight than the pigs with
      no lesions in the pars oesophagea. There was no difference between the prevalence
      of the oesophagogastric lesions of different severity between barrows and gilts,
      but there was evidence for differences between litters.

PMID- 7571253
TI  - Transmission of multi-resistant strains of Salmonella typhimurium from cattle to
      man.

PMID- 7571254
TI  - Absence of disease in mice receiving milk from cows with bovine spongiform
      encephalopathy.

PMID- 7571255
TI  - Live animal exports.

PMID- 7571256
TI  - Live animal exports.

PMID- 7571257
TI  - Live animal exports.

PMID- 7571258
TI  - Increased incidence in clostridial disease.

PMID- 7571259
TI  - Neospora abortion in cattle in Ireland.

PMID- 7571261
TI  - Oestrogens for mismating in the bitch.

PMID- 7571262
TI  - Sustainable use of wildlife.

PMID- 7571260
TI  - Diabetes in a chinchilla.

PMID- 7571263
TI  - A survey of the incidence of Neospora caninum infection in aborted and stillborn
      bovine fetuses in England and Wales.
AB  - Selected brains and fetal viscera from 190 aborted or stillborn bovine fetuses
      submitted to Veterinary Investigation Centres in England and Wales between August
      1992 and January 1993 were examined histologically. Non-suppurative inflammation
      of the brain and/or myocardium and placental cotyledons was identified by light
      microscopy in 20 (10.5 per cent). An immunocytochemical examination of fixed
      tissue sections using antisera against Neospora caninum, Toxoplasma gondii and
      Sarcocystis species revealed positive immunolabelling for N caninum in the brains
      of eight (4.2 per cent), but no labelling with anti-T gondii or anti-Sarcocystis
      species antisera was evident. These results suggest that N caninum may be an
      important cause of reproductive failure in cattle in England and Wales.

PMID- 7571264
TI  - Effects of injecting electronic transponders into the auricle of pigs.
AB  - Electronic transponders (3 x 18 mm) were injected into the base of the auricle of
      69 10-day-old pigs, 111 four-week-old pigs and 24 six-month-old pigs, to examine
      the procedure of injection in the auricle, the tissue reaction and the ease of
      removal from the carcase. The injection was difficult in the 10-day-old pigs, but
      was easier at four weeks. One of the 204 transponders were lost and five of them
      appeared to be broken. Only one gilt showed some exudate around the transponder.
      The transponders could easily be removed when the pigs were slaughtered by
      cutting off the ear. The position of the transponder was significantly (P < 0.05)
      more ventral in the animals injected at 10 days old than in those injected at
      four weeks. The mean thickness of the connective tissue capsule around the
      transponders increased at first (P < 0.1) and then decreased when they were
      injected into 10-day-old pigs but decreased (P < 0.1) from shortly after
      injection in the pigs injected at four weeks old. After five months, the capsule
      in the animals injected at 10 days old was on average significantly (P < 0.01)
      thinner than in those injected at four weeks.

PMID- 7571266
TI  - Influence of environmental contamination of a pig unit on chlortetracycline
      residues in pig tissues.

PMID- 7571265
TI  - Preliminary findings of ophthalmological abnormalities in farmed halibut.
AB  - Ocular abnormalities occurring in farmed halibut at the Sea Fish Industry
      Authority Marine Farming Unit, Ardtoe, Argyll were investigated clinically and
      post mortem. A significant number of fish were found to have posterior polar
      cystic changes either causing scleral ectasia or gross degenerative posterior
      segment abnormalities with chorioretinal atrophy. Other ocular abnormalities
      included cataract formation and intraocular inflammation. In a small number of
      fish gas bubble formation in the anterior chamber was observed during capture and
      examination. It is possible that the lesions seen in these fish are a form of gas
      bubble disease although super-saturation, the cause of gas bubble disease
      previously reported in farmed fish, does not occur in the tanks in which these
      fish are housed. While this paper provides no answers with regard to the
      aetiopathogenesis of the lesions, it is hoped that it will stimulate discussion,
      leading to resolution of these questions through a multidisciplinary approach to
      the problem.

PMID- 7571267
TI  - Histological and ultrastructural study of an unusual herpesvirus infection in
      owls (Tyto albus).

PMID- 7571268
TI  - Anthelmintic resistance of nematodes in sheep flocks in South America.

PMID- 7571269
TI  - Production of twin calves with in vitro fertilised embryos: effects on the
      reproductive performance of dairy cows.
AB  - Attempts were made to produce twin calves by implanting in vitro fertilised and
      matured (IVF) embryos into dairy cows. Twinning rates were consistently at the
      lower end of the range reported to have been obtained with in vivo derived
      embryos. The low pregnancy rates, higher than expected early embryonic losses,
      and increased fetal deaths and abortions recorded may indicate that IVF embryos
      are less viable. Fetal oversize in single calves was a significant problem in the
      first two years of the trial. The subsequent conception rates of cows that calved
      twins and those that calved singles were similar in spite of a much higher
      incidence of retained placenta and an increased interval to first oestrus in the
      cows bearing twins.

PMID- 7571270
TI  - Efficacy of moxidectin pour-on against nematode infections in cattle.
AB  - Three groups of eight calves, naturally infected with gastrointestinal nematodes
      and artificially infected with Dictyocaulus viviparus were used to evaluate the
      efficacy of moxidectin pour-on at dose rates of 0.35 mg/kg and 0.5 mg/kg
      bodyweight. With both doses the efficacy was 100 per cent against adult D
      viviparus, Trichostrongylus axei, Ostertagia species and Nematodirus helvetianus.
      It was more than 99 per cent against Ostertagia and Nematodirus species fourth
      stage larvae. A small number of Cooperia species were found after treatment, and
      for this parasite, the efficacy of moxidectin ranged from 97.6 per cent against
      the larval stages to 98.8 per cent against the adults. No adverse reactions to
      the moxidectin treatment were observed.

PMID- 7571271
TI  - Intracranial haemorrhage in a dobermann puppy with von Willebrand's disease.
AB  - Neurological examination of a lethargic, ataxic 12-week-old dobermann revealed
      decreased conscious proprioception in all its limbs. Haematological examination
      revealed a low platelet count. Cytological examination of a sample of
      cerebrospinal fluid revealed evidence of haemorrhage and chronic inflammation.
      The levels of von Willebrand's factor antigen were extremely low. Skull
      radiographs were consistent with mild hydrocephalus. Treatment resulted in little
      clinical improvement and the animal was euthanased. Post mortem examination of
      the brain revealed an internal hydrocephalus with haemorrhage into the
      ventricles. It was considered that the animal had suffered severe intracranial
      haemorrhage as a result of its low level of von Willebrand's factor antigen and
      that the bleeding may have been potentiated by the low platelet count.

PMID- 7571272
TI  - Pleuropulmonary abscessation in a horse caused by a gastric foreign body.

PMID- 7571273
TI  - Antibody response of sheep following administration of louping-ill virus vaccine.

PMID- 7571276
TI  - Hemicastration of thoroughbreds.

PMID- 7571275
TI  - MAFF policy and parasites.

PMID- 7571274
TI  - Bovine congenital erythropoietic protoporphyria in a pedigree Limousin heifer.

PMID- 7571277
TI  - Cat health care.

PMID- 7571278
TI  - Pro-inflammatory cytokines in a ruminant model: pathophysiological,
      pharmacological, and therapeutic aspects.
AB  - Infection evokes complex changes which are thought to be caused by production and
      release of pro-inflammatory cytokines such as tumour necrosis factor (TNF-alpha),
      interferons (INFs), and interleukins (ILs). They regulate local inflammatory
      reactions, but may also gain access to the circulation and induce systemic
      effects collectively known as the Acute Phase Response. To improve our
      understanding of the pathophysiology of pro-inflammatory cytokines in ruminants,
      studies have been performed with TNF-alpha, IL1-alpha/beta, and IFN-alpha/ gamma
      as well as with cytokine-inducers in dwarf goats. In relation to therapy, the
      following aspects may be of interest: a) Cytokine therapy given before or just
      after microbial challenge induces in vivo antimicrobial activity. Moreover,
      cytokines potentiate in vivo the antimicrobial activity of antibiotics, b)
      Cytokines may act as biological response modifiers for enhancing specific
      immunity to vaccines, and c) Cytokines may affect drug absorption, disposition,
      and metabolite formation in disease states. Although studies of the actions of
      corticosteroids, nonsteroidal anti-inflammatory and antipyretic agents,
      antibodies to endotoxin, TNF-alpha, or IL-1, synthetic E. coli lipid A
      precursors, hydrazine, isoniazid, chloroquine, polymyxin B, bicyclic imidazoles,
      hydroxamates, and tyrosine kinase inhibitors in endotoxaemic animals have shed
      further light on inflammatory processes, clinical studies in this field are
      urgently required to evaluate their beneficial effect.

PMID- 7571279
TI  - Ultrasonography in the diagnosis of congenital portosystemic shunts in dogs.
AB  - The value of ultrasonographic examination in the diagnosis of congenital
      portosystemic shunts was assessed in 36 dogs, using the right lateral approach.
      The sensitivity, specificity, and accuracy were 0.74, 1.0, and 0.86 respectively.
      The conclusion is that ultrasonography is highly specific and reasonably
      sensitive in diagnosing congenital portosystemic shunts in dogs.

PMID- 7571280
TI  - Liver triacylglycerol concentrations around parturition in goats with either pre
      partum restricted or free access to feed.
AB  - The hypothesis was tested that goats allowed ad libitum access to feed during the
      dry period develop higher post partum hepatic triacylglycerol concentrations than
      do goats given a restricted amount of feed during the dry period. Goats in their
      second or more pregnancies were either given a restricted amount of hay, maize
      silage and concentrate (n = 5) or had free access to this feed mixture while the
      composition was kept constant (n = 11). After parturition both groups were
      allowed ad libitum access to feed. Post partum liver triacylglycerol
      concentrations, as measured in liver biopsies, were significantly raised in goats
      allowed ad libitum access to feed during the dry period. The increase in liver
      triacylglycerols was associated with slightly higher plasma concentrations of non
      esterified fatty acids but lower serum 3-hydroxybutyrate concentrations. The
      feeding regimen during the dry period did not significantly influence post partum
      liver glycogen concentrations and serum levels of glucose, cholesterol, and
      insulin. The increase in post partum liver triacylglycerol concentrations in the
      goats allowed ad libitum access to feed instead of a restricted ration during the
      dry period, was associated with a significant rise in serum alkaline phosphatase
      activities, whereas other liver function and cell damage indicators in serum,
      i.e. aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl
      transpeptidase, and bilirubin, were unchanged. Feed intake after parturition
      tended to be higher in the goats allowed ad libitum access to feed during the dry
      period but milk production was significantly raised.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7571281
TI  - Polyglandular deficiency syndrome in a boxer dog: thyroid hormone and
      glucocorticoid deficiency.
AB  - Primary hypothyroidism and partial primary adrenocortical deficiency (isolated
      glucocorticoid deficiency) were diagnosed in an 8-year-old spayed female boxer
      dog, presented because of progressive symmetrical truncal alopecia, lethargy, and
      intolerance to cold. The diagnosis was based upon the combination of low, non-TSH
      responsive concentrations of plasma thyroxine and low urinary excretion of
      corticoids together with high plasma concentrations of ACTH. Normal
      suppressibility of ACTH concentrations by a low dose of dexamethasone indicated
      an intact feedback system. Plasma growth hormone levels were elevated, most
      probably because somatostatin release was depressed by the glucocorticoid
      deficiency. The dog improved during oral replacement therapy with thyroxine until
      death ensued after 9 months as a result of intercurrent disease. Autopsy revealed
      thyroid atrophy and lymphocytic adrenalitis with complete destruction of the zona
      fasciculata and zona reticularis of the adrenal cortex. The combination of
      primary hypothyroidism and primary adrenocortical deficiency in this dog is
      identical to the entity known as type II polyglandular autoimmunity or Schmidt's
      syndrome in humans. The adrenocortical insufficiency remained confined to
      glucocorticoid deficiency during the observation period; on no occasion did
      electrolyte concentrations in the plasma reach values suggestive of
      mineralocorticoid deficiency.

PMID- 7571282
TI  - Diagnosing salmonellosis in horses. Culturing of multiple versus single faecal
      samples.
AB  - Three rectal faecal samples were taken at 24-hour intervals from 136 horses in
      order to investigate whether multiple faecal cultures yield a greater number of
      Salmonella-positive horses compared to single faecal cultures. Of these 136
      horses, 89 were suspected of salmonellosis on clinical grounds and 47 belonged to
      a control group. From the 'Salmonella suspected' group, 22 horses (25%) were
      Salmonella positive on one or more occasions. Only twelve of these 22 positive
      horses (55%) were positive at first sampling. Of the control group, only three
      horses (6%) were positive for Salmonella. Thirty-one (69%) of the 45 positive
      cultures from the 'Salmonella suspected' group were found only after enrichment
      in Selenite broth. From the results of the present study it is concluded that
      multiple faecal cultures are superior to single faecal cultures for diagnosing
      clinical salmonellosis in horses and that there is no relation between the course
      of the disease and whether the Salmonellae were cultured directly or indirectly,
      after enrichment in Selenite broth. Salmonellae were cultured from the faeces of
      horses treated with antibiotics before their referral, even when the isolated
      strain was sensitive to the antimicrobial drug used by the practitioner.

PMID- 7571283
TI  - Cytophilic antibodies in cats with miliary dermatitis and eosinophilic plaques:
      passive transfer of immediate-type hypersensitivity.
AB  - Passive cutaneous anaphylaxis test and Praunitz-Kustner tests were performed in
      healthy recipient cats with heated and unheated sera of 17 cats suspected of
      having allergic dermatitis and of 12 healthy control cats. Positive reactions
      occurred with heated and unheated sera. It was therefore hypothesized that a heat
      stabile cytophilic antibody is involved in the pathogenesis of eosinophilic
      plaques and miliary dermatitis in some cats.

PMID- 7571284
TI  - Circulatory disorders of the liver in dogs and cats.
AB  - This paper presents a review of the literature on hepatic circulation and
      circulatory disorders of the liver in the dog and cat, and also includes a number
      of our own not previously published data. Circulatory disorders of the liver are
      frequently observed in dogs and cats. These disorders can be divided into
      congenital portosystemic shunts, disorders associated with outflow disturbances,
      and disorders associated with portal hypertension. Outflow disturbances result in
      passive congestion of the liver and in both species are mainly due to cardiac
      failure. Portal hypertension with resultant portosystemic collateral circulation
      and ascites mainly results from chronic liver disease, particularly cirrhosis.
      The main vascular disorder resulting in portal hypertension and ascites in the
      dog is primary hypoplasia of the portal vein.

PMID- 7571285
TI  - Abdominal drainage in ten dogs with septic peritonitis.

PMID- 7571286
TI  - Diagnosis and treatment of gastric disease.

PMID- 7571287
TI  - Diagnosis and treatment of chronic diarrhea.

PMID- 7571288
TI  - Diagnosis and treatment of hepatic disease.

PMID- 7571289
TI  - Feline asthma syndrome.

PMID- 7571291
TI  - Growth hormone: its clinical relevance.

PMID- 7571290
TI  - Cowpox in cats and man.

PMID- 7571293
TI  - The treatment of hernias.

PMID- 7571292
TI  - The differential diagnosis of polyuria/polydipsia in dogs.

PMID- 7571294
TI  - von Willebrand's disease in Dutch Kooiker dogs.

PMID- 7571295
TI  - Variable structures of mitochondrial DNA in dogs.

PMID- 7571296
TI  - FIP, easy to diagnose?

PMID- 7571297
TI  - Cytostatic treatment in veterinary medicine.

PMID- 7571298
TI  - Diagnosis of cardiac disease.

PMID- 7571299
TI  - Photosynthesis of vitamin D in the skin of dogs cats and rats.

PMID- 7571300
TI  - Diagnostic imaging in dogs: radiography, ultrasonography, and computed tomography
      for examination of the abdomen.

PMID- 7571301
TI  - Basic principles of thoracic radiography.

PMID- 7571302
TI  - Arthroscopy in the diagnosis and treatment of front leg lameness.

PMID- 7571303
TI  - Echocardiography in dogs.

PMID- 7571305
TI  - Immune mediated skin diseases.

PMID- 7571304
TI  - The use of iohexol to measure glomerular filtration rate in the dog.

PMID- 7571306
TI  - The skin in systemic disease.

PMID- 7571307
TI  - Diagnosis and treatment of porto-systemic shunts.

PMID- 7571309
TI  - Diagnosis and treatment of conjunctival and corneal diseases.

PMID- 7571310
TI  - Retinal diseases: an update.

PMID- 7571308
TI  - Skin disorders in cats.

PMID- 7571311
TI  - The role of tonometry in the clinical management of the glaucomas in companion
      animals.

PMID- 7571313
TI  - Clinical, electrophysiological, and morphological findings in a case of neuronal
      ceroid lipofuscinosis in the Polish Owczarek Nizinny (PON) dog.

PMID- 7571312
TI  - Eye lesions in Turkish dancing bears.

PMID- 7571314
TI  - Rod dysplasia and early retinal degeneration in a young Briard sheepdog.

PMID- 7571316
TI  - Cataracts in rapidly growing farm raised Atlantic salmon (Salmo salar).

PMID- 7571315
TI  - Polymerase chain reaction: a revolution in diagnosis of ocular leishmaniosis?

PMID- 7571317
TI  - Changing the way we practice: how to thrive and not just survive in veterinary
      medicine.

PMID- 7571318
TI  - Knee joint function, meniscal disease, and osteoarthritis.

PMID- 7571319
TI  - Diseases of the respiratory tract in psittacine birds.

PMID- 7571320
TI  - The nutritional requirements of ornamental fish.

PMID- 7571321
TI  - Neural regulation of swallowing in the dog.

PMID- 7571322
TI  - Dyspnea: how to solve the problem.

PMID- 7571323
TI  - An update in dentistry.

PMID- 7571324
TI  - Distal extremity mesh grafts in nine dogs and one cat.

PMID- 7571325
TI  - World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.)
      second edition of guidelines for evaluating the efficacy of anthelmintics in
      ruminants (bovine, ovine, caprine)
AB  - The first edition of the W.A.A.V.P. anthelmintic guidelines for ruminants was
      published in 1982. Since then improved parasitological procedures have been
      developed, new therapeutic and prophylactic products have appeared requiring
      different test methods, and registration authorities are requesting more detailed
      record keeping and data validation. This second edition addresses these
      developments and fulfills the original goal of publishing guidelines for high
      quality, scientifically valid testing standards for trials that would be accepted
      as proof of efficacy by registration authorities regardless of country of origin.
      This second edition includes updated guidance on standard parasitological
      procedures, dose titration, dose confirmation and clinical trials, and provides
      guidelines for evaluating products for efficacy against anthelmintic resistant
      parasites, persistence of activity and prophylactic activity. Tests for efficacy
      against nematodes, trematodes and cestodes are included.

PMID- 7571326
TI  - Disposition of diminazene aceturate (Berenil) in trypanosome-infected pregnant
      and lactating cows.
AB  - Three cows were repeatedly infected with different strains of Trypanosoma
      congolense and treated intramuscularly each time with a different dose of
      diminazene aceturate (Berenil). Biphasic decline was observed of the maximal
      plasma drug levels, which were attained at 15 min after the first treatment and
      at 30 min after the second and third treatments. The rate constants for the
      distribution and terminal phases depended on the period of exposure to
      parasitaemia of the animal at the time of treatment. Maximal diminazene aceturate
      residue levels were found in milk 8 h post treatment and declined biexponentially
      to 4.56 ng ml-1 and 8.76 ng ml-1 at 21 days post treatment after 3.5 mg kg-1 and
      7.0 mg kg-1 doses, respectively. In the three cows, higher drug residues were
      found in the kidney (7.04, 3.92 and 7.99 micrograms g-1) than in liver (3.26,
      2.87 and 1.24 micrograms g-1) and heart (1.79, 1.25 and 1.03 micrograms g-1). The
      results of this study indicate that the level of parasitaemia (degree of anaemia)
      in the animal at the time of treatment affects the distribution, disposition and
      elimination of diminazene aceturate in the animal. Furthermore, the residue level
      in milk after treatment depends on the treatment dose and could easily be
      bioavailable to the consumer.

PMID- 7571327
TI  - The effect of L-thyroxine on the anaemia response in Trypanosoma congolense
      infected rabbits.
AB  - The development of anaemia is a major pathological manifestation in chronic
      trypanosomosis. The anaemia in African trypanosomosis coincides with a marked
      decrease in plasma concentration of both thyroxine (T4) and 3,5,3'
      triiodothyronine (T3). To evaluate the effect of trypanosome-induced
      hypothyroidism on the development of anaemia, sexually mature white New Zealand
      rabbits were used. Three groups were set up, each of ten rabbits: one group was
      infected with Trypanosoma congolense; the second group was infected but given
      replacement doses of thyroxine (treated); the third group was not infected. Small
      volumes of blood were collected for the determination of parasitaemia and packed
      cell volume (PCV). The concentrations of T3 and T4 were measured in plasma by
      radioimmunoassay. The decrease in PCV correlated closely (y = -0.38x + 15.2; r =
      0.82, P = 0.001) with the intensity and duration of parasitaemia. The critical
      PCV value was 0.15 11-1 with a peak parasitaemia of approximately 5 x 10(6)
      trypanosomes ml-1 of blood. There was a significant correlation between the
      plasma T3 and PCV (y = 0.049x + 0.57; r = 0.66, P = 0.020). There was also a good
      positive correlation between T4 and PCV (y = 14.5 + 3.03; r = 0.95, P < 0.001) in
      the infected untreated group. The PCV levels were significantly different among
      the three groups of animals (P < 0.05). The infected-treated animals sustained
      longer periods of infection than the infected and untreated ones. The sustained
      physiological level of bioactive thyroid hormones T3 and T4 significantly
      arrested the decline in PCV as the disease progressed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7571328
TI  - Detection of circulating antigen in sera of Fasciola gigantica-infected cattle
      with antibodies reactive with a Fasciola-specific 88-kDa antigen.
AB  - Antibodies against a specific 88-kDa antigen of Fasciola gigantica were used for
      the detection of circulating antigen in the sera of cattle with experimental and
      natural infections of F. gigantica by a double antibody ELISA. Circulating
      antigen was detectable as early as the second and third weeks after infection and
      positive absorbance values were obtained for the entire duration of infection.
      Absorbance values decreased below the cutoff point 3 weeks after chemotherapy
      with oxyclozanide. This immunoassay also greatly enhanced the specificity of
      immunodiagnosis of fasciolosis in naturally infected cattle. The test system has
      excellent potential for the accurate diagnosis of ruminant fasciolosis.

PMID- 7571330
TI  - Streptavidin-reactive protein in Fasciola hepatica.
AB  - Streptavidin-binding protein was found in an extract of Fasciola hepatica, and
      the protein was analyzed by the inhibition assay using avidin or D-biotin, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western
      blotting using peroxidase-conjugated streptavidin. Inhibition assays revealed
      that the protein could bind to streptavidin by a mechanism similar to the avidin
      biotin reaction, and the molecular size of the protein was estimated by SDS-PAGE
      to be 71.7 kDa.

PMID- 7571331
TI  - Comparative effects of nematode infection on Bos taurus and Bos indicus crossbred
      calves grazing on Argentina's Western Pampas.
AB  - Breed differences in resistance or tolerance to naturally acquired
      gastrointestinal nematodes were compared between Aberdeen Angus (AA) and Santa
      Gertrudis (SG) weaned steer calves grazing in a temperate environment. Within
      breeds, one half of the calves was untreated: AAU (n = 17) and SGU (n = 18) while
      the other half was treated with moxidectin monthly: AAT (n = 14) and SGT (n =
      14). All calves were grazed on the same contaminated pasture from autumn to
      winter, when each group was separated to uninfected paddocks for the remaining
      period of the study. Faecal egg counts, plasma pepsinogen levels (PPL), herbage
      larval counts and liveweight (LW) were recorded monthly. Egg counts and PPL of
      AAU and SGU increased from autumn to early winter when calves showed heavy
      parasitism (mainly Trichostrongylus axei) and severely sick calves needed
      emergency treatment. On the clean paddocks, parasitological parameters
      progressively decreased. Late winter egg counts were higher (P < 0.05) in SGU
      than in AAU. PPL of SGU were higher than AAU ones, but no significant differences
      were detected. Larval differential counts of SGU showed fewer Cooperia (P < 0.08)
      and higher T. axei (P < 0.002) proportions than those of AAU. Numbers of severely
      sick and dead SGU calves (61%) were greater (P < 0.01) than those numbers of AAU
      calves (17.5%). Cumulative LW gains differences within SG breed were higher (P <
      0.0001) than those differences within AA breed (P < 0.003). LW gains of AAU
      during autumn-winter period were greater (P < 0.002) than those of SGU.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571329
TI  - Time-course analysis of antibody response by EITB and ELISA before and after
      chemotherapy in sheep infected with Fasciola gigantica.
AB  - The time-course analysis of the antibody response to Fascicola gigantica
      infection in sheep was studied by enzyme-linked immunosorbent assay (ELISA) and
      enzyme-linked immunoelectrotransfer blot (EITB). Sera from sheep experimentally
      infected with F. gigantica were reacted with excretory-secretory antigens of the
      worm before and after chemotherapy with oxyclozanide. In ELISA, there was a
      significant increase in anti-Fasciola antibody by 2 weeks after infection and
      there was a sharp decrease in antibody titer by 4 weeks after treatment. By EITB,
      the infected sheep sera recognised four polypeptides in the range of 43-75 kDa as
      early as 2 weeks after infection, with more polypeptides being recognised as the
      infection progressed. Recognition of an 87 kDa antigen was lost by 2 weeks after
      treatment and is therefore a good marker for treatment efficacy. Comparative
      immunoblotting with sheep anti-Paramphistomum, anti-Dicrocoelium and anti
      Fasciola sera revealed that the 17 kDa, 21 kDa, 57 kDa and 69 kDa proteins are
      specific to fasciolosis and are good antigens for early and specific
      immunodiagnosis of F. gigantica infection in sheep.

PMID- 7571332
TI  - Donkey klossiellosis in Kenya.
AB  - Out of eight donkeys examined, two had gametogonic and sporogonic stages of
      Klossiella equi in their kidneys. Gametogonic stages included microgametocytes
      and macrogametocytes, some of them in syzygy. They were found in enlarged
      parasitophorous vacuoles situated in epithelial cells of the renal tubules.
      Sporonts were seen in the epithelial cells protruding into the tubular lumen
      while sporoblasts, sporocysts and sporozoites were found freely in the tubular
      lumen. Entire sporocysts were rarely encountered but sporozoites liberated from
      the ruptured sporocysts could be seen. No inflammatory reaction could be
      attributed to the presence of these parasites.

PMID- 7571333
TI  - Comparison between an enzyme-linked immunosorbent assay using a detergent-soluble
      Leishmania infantum antigen and indirect immunofluorescence for the diagnosis of
      canine leishmaniosis.
AB  - Serum samples collected from 290 dogs--186 Leishmania-infected and 104 control
      animals--were screened to detect the presence of specific antibodies to
      Leishmania infantum antigens in Tuscany, Italy. Two different techniques were
      compared: an indirect immunofluorescence assay (IFA) and an indirect enzyme
      linked immunosorbent assay (ELISA). The ELISA was developed using a detergent
      soluble antigen of L. infantum promastigotes. Triton X-100 and protease
      inhibitors were used as detergent and to increase reproducibility of the assay,
      respectively. A strong correlation between the anti-Leishmania antibody levels
      obtained by ELISA and those obtained using IFA was observed. The ELISA appeared
      to be somewhat more sensitive than IFA (99.5% vs. 98.4%), while its specificity
      was lower (97.1% vs. 100%), even if not significantly different. Immunoblotting
      analysis, using the detergent-soluble L. infantum antigen, demonstrated that
      proteins of M(r) 30 and 73 kDa were recognized by all positive sera, regardless
      of the serum titre. Furthermore, antigens of M(r) 16, 18, 26, 33, 50 and 117 kDa
      were also frequently reactive with a large proportion of sera from infected dogs.
      This ELISA demonstrated a high sensitivity and specificity as well as the IFA,
      and it seems to be a suitable assay for large scale epidemiological studies.

PMID- 7571334
TI  - Studies of experimental infection and cross-immunity between stocks of Cowdria
      ruminantium in Sokoto red goats.
AB  - The course of experimental infection and cross-immunity tests between stocks of
      Cowdria ruminantium were investigated using eight infected and four uninfected
      control Sokoto red goats. All eight infected goats reacted to the primary
      infection. The incubation period varied between 8 and 23 days. During the febrile
      reaction, the highest rectal temperature recorded was 40 degrees C and the lowest
      was 39.7 degrees C, compared with a range of 38.6 +/- 0.15 to 38.1 +/- 0.19 in
      control goats. Following the primary infection, each of the animals was treated
      with long-acting Tetracycline (Terramycin, Pfizer) at a dose of 20 mg kg-1 body
      weight to control the resulting temperature reaction. They were reinfected with
      the homologous stock 3 weeks after treatment to demonstrate whether they had
      become immune. The homologous challenge did not give any temperature reaction
      during 3 weeks of monitoring. They were then challenged with the heterologous C.
      ruminantium stock. This did not result in a febrile reaction during 3 weeks of
      monitoring. The observed cross-protection indicates antigenic similarity between
      the two stocks.

PMID- 7571335
TI  - Different patterns of faecal egg output following infection of Scottish blackface
      lambs with Ostertagia circumcincta.
AB  - Faecal nematode egg counts were monitored in 184 Scottish Blackface lambs during
      natural exposure to a mixed, predominantly Ostertagia circumcincta infection and
      12 lambs were selected which showed consistently zero (low count group; nine
      lambs) or consistently positive faecal egg counts (high count group; three
      lambs). These lambs were then treated with anthelmintic and challenged with
      50,000 infective larvae of O. circumcincta and monitored thrice-weekly for 38
      weeks; they were then re-challenged with another 50,000 infective larvae of O.
      circumcincta and monitored for a further 8 weeks. All sheep gave positive egg
      counts following deliberate infection. However, there was considerable variation
      among sheep in the size and timing of the peak in egg production. In particular,
      the pattern of mean values for faecal egg counts was different in the two groups.
      Egg counts were lower in the later periods of the extended infection in both
      groups of sheep. During the first half of the extended infection, egg counts were
      lower in sheep from the low count group, but during the second half of the
      infection the pattern was reversed and egg counts were lower in sheep from the
      high count group. There was a weak positive correlation between egg counts
      following anthelmintic treatment and 28 days exposure to natural infection and
      egg counts 28 days after a deliberate infection. Egg counts in the later stages
      of the deliberate infection were strongly but negatively correlated with egg
      counts following natural infection. The results of these studies show that
      differences in egg count following natural infection can be reproduced in
      experimental infections and that there is substantial variation in the pattern of
      egg production over time in different sheep. They also suggest that naturally
      resistant lambs are better able to delay worm development than naturally
      susceptible lambs.

PMID- 7571336
TI  - Epidemiological studies on intestinal helminth parasites of rural and urban red
      foxes (Vulpes vulpes) in the United Kingdom.
AB  - An epidemiological study of intestinal helminths in 843 foxes (Vulpes vulpes)
      from southern England revealed the presence of 13 parasite species: five
      nematodes--Toxocara canis (prevalence 55.9%), Toxascaris leonina (1.5%),
      Uncinaria stenocephala (68.0%), Trichuris vulpis (0.5%) and Capillaria aerophila
      (0.2%); four cestodes--Taenia pisiformis (13.8%), Taenia hydatigena (2.5%),
      Echinococcus granulosus (0.1%) and Dipylidium caninum (3.8%); two trematodes-
      Brachylaima recurva (2.9%) and Cryptocotyle lingua (2.3%); two acanthocephalans-
      Prosthorhynchus transversus (0.7%) and Macracanthorhynchus catulinus (0.1%).
      Trichuris vulpis, Brachylaima recurva, Macracanthorhynchus catulinus and
      Prosthorhynchus transversus are new host records for the UK. Results are
      discussed with reference to variations in the diets of urban and rural foxes and
      to their potential as reservoir hosts for helminths of medical and veterinary
      importance.

PMID- 7571337
TI  - Evidence for the role of the sheep biting-louse Bovicola ovis in producing
      cockle, a sheep pelt defect.
AB  - The prevalence and severity of cockle, a sheep pelt defect characterised by
      raised lumps, was assessed on lambs that were either louse-infested (Bovicola
      ovis) or louse-free at birth. Assessments were made on pickled pelts, 10 months
      after the lambs had entered the trial. Lambs kept free of lice did not develop
      cockle, whereas the defect was common in lambs (about 90%) that were infested
      with lice. There was a direct correlation between louse scores and cockle, high
      louse scores being associated with a more severe degree of cockle. The results
      give support to the strong causal relationship between B. ovis and cockle, but
      questions such as the minimum number of lice needed to cause cockle and the time
      required for cockle to develop still need to be answered.

PMID- 7571338
TI  - Salivary glands and saliva of Amblyomma variegatum ticks: comparison of immatures
      and adults in relation to the pathogenesis of dermatophilosis.
AB  - Salivary glands from immature and adult Amblyomma variegatum were compared for
      differences in potential components responsible for the systemic aggravation by
      adult ticks of the skin disease dermatophilosis. Whole salivary glands from
      adult, nymphal and larval A. variegatum ticks were compared for structural
      differences by light microscopy and for protein content by gel electrophoresis.
      Type-2 salivary gland acini from adult ticks at the second stage of feeding
      contained significantly greater (P < 0.01) proportions of c1 secretory granules
      than those from either of the immature instars. There was also significantly more
      area occupied with e secretory granules in the type-3 salivary gland acini from
      adult ticks compared with larval ticks. Electrophoresis of whole salivary glands
      showed seven bands present only in the adult material; of these, three were dense
      bands at 37, 35 and 31 kDA. Electrophoresis of saliva from adult and nymphal A.
      variegatum obtained by artificial stimulation showed that nine bands were unique
      to the saliva produced by adults; of these nine bands one was a dense band at 67
      kDa. It was concluded that adult salivary material was different from that of
      immature ticks and that further studies on the relationship between the feeding
      of adult A. variegatum and dermatophilosis should investigate these components
      unique to the adults.

PMID- 7571339
TI  - Efficacy of pyrantel tartrate against experimental infections with Haemonchus
      contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis in goats.
AB  - The efficacy of pyrantel tartrate was evaluated in goats against induced
      infections with Haemonchus contortus, Teladorsagia circumcincta and
      Trichostrongylus colubriformis. All the strains were of sheep origin and tested
      for susceptibility to pyrantel tartrate in sheep at the standard dose rate (20 mg
      kg-1) prior to the infection of goats. Fifteen French Alpine female goats were
      inoculated with the three nematode species. On Day 25 post-infection, goats were
      randomized into an untreated control group and two pyrantel treatment groups (20
      mg kg-1 bodyweight once, and 40 mg kg-1 bodyweight as two doses 24 h apart). The
      goats were killed and processed for worm recovery 10 days after treatment. The
      two dose rates achieved high and similar levels of efficacy (> 96%) against
      Haemonchus contortus and Teladorsagia circumcincta. Against Trichostrongylus
      colubriformis, however, pyrantel tartrate was less effective at both dose rates
      as worm reductions ranged from 55 to 62%.

PMID- 7571340
TI  - Persistence of Tritrichomonas foetus in naturally infected cows and heifers in
      Argentina.
AB  - Tritrichomonas foetus infection was investigated in 76 pregnant and 64 non
      pregnant cows slaughtered in the local abbattoir and in two different lots of
      first-service heifers that were found to be non-pregnant 60 days post breeding
      (PB). In live and slaughtered animals, mucus samples were obtained from the
      vagina and from the vagina and uterus, respectively, using a "screw-head scraper
      rod". In pregnant cows, samples of amniotic and allantoid fluid were also
      collected, as well as samples from the stomach contents of the fetuses. All
      samples were cultured in Modified Plastridge Medium. T. foetus was isolated from
      three pregnant and two non-pregnant slaughtered cows. Parasites were recovered
      from the vagina of these five cows, as well as from the uterus in two cases and
      from the fetus in one case. Lot I of first-service heifers consisted of 323
      females from eight different farms. Bulls infected with T. foetus from these
      farms were culled or treated, and heifers found empty at diagnosis of pregnancy
      were culled. Lot II consisted of 120 heifers from a single farm where T. foetus
      was controlled only in bulls. All heifers from Lot I were T. foetus negative. In
      Lot II, 12 of 120 heifers (10%) were T. foetus positive. In ten of these the
      parasites were observed once, in one at 60 days PB, in seven at 160 days PB and
      in two at 240 days PB; in the remaining two infected heifers, an irregular
      pattern of isolation persisted during 300 days PB. On the basis of these results,
      control methods are discussed and analysed.

PMID- 7571341
TI  - Prevalence of Toxoplasma gondii antibodies in cats in the western part of Great
      Buenos Aires, Argentina, 1993.
AB  - The serological prevalence of Toxoplasma gondii was determined, using indirect
      haemagglutination assay, in the sera of 169 cats. Classification by age, sex,
      alimentary, hunting and roaming habits was made in conjunction with the number of
      cats living in each house. An important prevalence was detected (19.5%) from 1
      year of age and statistical significance was found in those animals that had
      predatory habits or lived in groups.

PMID- 7571342
TI  - Prevalence of IgG antibodies to Trichinella spiralis in dogs in Macedonia,
      northern Greece.
AB  - An enzyme-linked immunosorbent assay (ELISA) was used to detect T. spiralis
      infection in dogs, using larval T. spiralis excretory-secretory (ES) antigen.
      Forty-three (4.3%) dog sera out of 1000 revealed the presence of IgG T. spiralis.
      The positive sera were distributed in three groups; 21 (2.1%) weakly positive, 14
      (1.4%) moderately positive, and eight (0.8%) strongly positive.

PMID- 7571343
TI  - Effects of cadmium and verapamil on ketamine-induced anesthesia in mice.
AB  - Previous studies have shown that pretreatment with cadmium and verapamil
      potentiated the effects of some CNS active drugs. The objective of this study was
      to determine the influence of these agents on ketamine anesthesia in adult male
      mice. Intraperitoneal administration of 300 mg ketamine/kg produced sleeping time
      of 40.88 +/- 2.98 min. Pretreatment with a single dose of either 3 mg cadmium/kg
      sc or 5 mg verapamil/kg ip alone significantly increased the duration of sleeping
      time (40.88 +/- 2.98 vs 55.09 +/- 4.20 and 49.01 +/- 3.09 min). Pretreatment with
      cadmium plus verapamil produced significant additive effects on ketamine-induced
      anesthesia (40.88 +/- 2.98 vs 70.32 +/- 4.64 min). Pretreatment with 3 mg
      cadmium/kg sc before 1 w caused a reduction in the potentiating effects of a 2nd
      dose of cadmium in ketamine-induced anesthesia in mice. These results indicate
      that prolongation of ketamine-induced anesthesia by cadmium and verapamil could
      be mediated either by inhibition of hepatic P450 metabolizing enzymes or neuronal
      calcium channels blockade. The tolerance to the potentiating effects of cadmium
      could be mediated by hepatic metallothionein induction and a reduction in total
      body cadmium burden.

PMID- 7571344
TI  - Effect of cadmium in the zinc deficient rat.
AB  - Three-w-old male Sprague-Dawley rats were given a zinc (Zn)-deficient (0 ppm Zn)
      or a Zn-adequate diet (30 ppm Zn) supplemented with 0, 0.5 or 100 ppm cadmium
      (Cd) for up to 5 mo. The proximal convoluted tubules of the kidneys had
      degenerative changes in the rats fed the Zn-deficient diet containing 100 ppm Cd
      [Zn 0, Cd 100], but there were no lesions in other groups. Electron microscopy
      showed cytoplasmic vacuolation of the proximal tubules, mitochondrial swelling
      and coagulative necrosis in Zn 0:Cd 100 rats. The present study revealed
      diminished bone growth and cortical thinning of the femur, but there was no
      osteomalacia seen in Itai-Itai disease patients. The results indicate that Zn
      deficiency may enhance the renal toxicity of Cd, but that dietary Cd did not
      cause osteomalacia even under severe Zn-deficient conditions.

PMID- 7571345
TI  - Fed before diethylnitrosamine, Fusarium moniliforme and F proliferatum mycotoxins
      alter the persistence of placental glutathione S-transferase-positive hepatocytes
      in rats.
AB  - Groups of 5-w-old F344/N female rats were fed a semipurified diet for 13 w with
      or without 20 mg fumonisin B1/kg provided from an aqueous extract of Fusarium
      moniliforme-corn culture. After 1 w, a single dose of 30 mg diethylnitrosamine
      (DEN)/kg was given orally. Twelve weeks later, the presence of placental
      glutathione S-transferase-positive (PGST-[+]) hepatocytes were
      immunohistochemically quantified. Rats given DEN and the FB1-containing diet for
      1 or 13 w developed 4-fold more PGST-[+] hepatocytes than rats given DEN alone.
      In a second study, male and female F344/N rats were fed 20 mg purified FB1/kg
      diet or F proliferatum-corn culture material containing 20 mg FB1/kg diet for 1 w
      before DEN treatment. One week after DEN treatment, male rats fed the F
      proliferatum-corn culture material had significantly fewer PGST-[+] hepatocytes
      than those fed DEN with or without purified FB1. At 9 w after DEN treatment, PGST
      [+] cells in female rats given DEN and fed F proliferatum-corn culture material
      were more persistent than in rats given DEN alone. Males given DEN and fed FB1 or
      F proliferatum culture material had significantly fewer PGST-[+] hepatocytes than
      males given DEN alone. These results suggest that F moniliforme and F
      proliferatum components are cocarcinogens in females. In males, however, FB1 and
      unidentified F proliferatum components reduced the persistence of DEN-initiated
      preneoplastic hepatocytes.

PMID- 7571346
TI  - Toxicity of cotoran (fluometuron) in Desert sheep.
AB  - Twelve of fifteen 6-9-mo-old clinically healthy Desert sheep were given single or
      repeated daily doses of 25 to 4000 mg cotoran/kg by drench. Cotoran poisoning was
      characterized by grinding of the teeth, ruminal tympany, mydriasis, dyspnea,
      staggering, paresis of the hind and forelimbs, and recumbency. Lesions were
      widespread congestion and hemorrhage, hepatic fatty change, catarrhal enteritis
      and degeneration of the epithelial cells of the renal proximal convoluted
      tubules. These were accompanied by significant increases in the activities of
      GOT, LDH and GGT and decreases in serum total protein and calcium.

PMID- 7571347
TI  - Treatment of ammonia intoxication in rats through the use of amino acids from the
      urea cycle.
AB  - To evaluate the effectiveness of the treatment of severe ammonia intoxication
      with amino acids from the urea cycle (arginine, citrulline and ornithine) and
      alpha-ketoglutarate, 371 rats were used. The rats were poisoned with a lethal ip
      dose (99.9%) of ammonium acetate. Five min later they were treated with
      bidistilled water (control) or with standard urea-cycle mixed amino acid
      solutions containing 2, 4 or 6 mM arginine/kg bw as the marker basic amino acid
      or 2 mM arginine + 4 mM alpha-ketoglutarate/kg bw. The clinical picture and
      plasma urea concentration were followed. All 4 treatment groups had higher
      survival rates (20.83%-35.71%) than did the controls (1.18%). Surviving animals
      had a less severe clinical picture and presented fewer convulsive episodes than
      did fatally-poisoned rats. The higher doses of arginine increased the mean
      survival time of rats which died. The overall mean plasma urea concentration in
      surviving rats was higher (75.1 +/- 10.8 mg/dL) than in fatally-poisoned rats
      (44.4 +/- 4.9 mg/dL). Treatment with urea-cycle amino acids increased hepatic
      detoxication of ammonia; however, there was no relationship between the doses
      used and survival rates. There was no apparent synergism between urea-cycle amino
      acids and alpha-ketoglutarate.

PMID- 7571348
TI  - Developmental toxicity of the substituted phenylurea herbicide isoproturon in
      rats.
AB  - Isoproturon, a substituted phenylurea herbicide, was studied for its toxicity to
      dams and its potential fetotoxic/teratogenic effects in the fetuses of albino
      rats. Isoproturon technical administered orally at 45, 90 or 180 mg/kg/d to dams
      during d 6-20 of pregnancy did not produce maternal toxicity at 45 or 90 mg/kg/d.
      However, 180 mg isoproturon/kg/d caused changes in maternal enzymes and chromatid
      breaks. There was no fetotoxic/teratogenic effect of isoproturon at the tested
      dosage levels in number of implantations, percent resorption, fetal weights, and
      external, visceral and skeletal fetal observations.

PMID- 7571349
TI  - Protein binding of acetylsalicylic acid and salicylic acid in porcine and human
      serum.
AB  - As part of a pilot project establishing a porcine model for aspirin overdose, the
      percentage protein binding of acetylsalicylate (ASA) and salicylate (SA) in
      porcine and human sera was evaluated in vitro over a range of concentrations.
      Serum from 2 pigs and 4 humans were spiked with ASA concentrations of 0.5-100
      mg/dL and SA concentrations of 1-120 mg/dL. Protein binding for each
      concentration of ASA and SA was determined using radiolabeled drug and
      ultrafiltration with the Centrifree micropartition system. The percentage protein
      binding for ASA in pig and human sera were similarly low (< 50%) for all
      concentrations evaluated. Percentage protein binding for SA for pig and human
      sera were high (approximately 90% and 80%) at low therapeutic concentrations, but
      then declined to approximately 30% at higher toxic concentrations (120 mg/dL).
      The protein binding of ASA and SA over a range of concentrations was similar for
      porcine and human sera.

PMID- 7571350
TI  - Coefficient of distribution of some organophosphorous pesticides in rat tissue.
AB  - Coefficient of distribution in tissue is proposed as an indicator of the affinity
      of xenobiotics for different tissues and their tendency to accumulate. The
      present study shows the distribution of some organophosphorous pesticides in rat
      tissues. Using the coefficient of distribution we established the preference of
      these insecticides for the various tissues. Each pesticide had a specific pattern
      of affinity for different tissues.

PMID- 7571351
TI  - Treatment of lead toxicity in calves.
AB  - Thiamine hydrochloride alone or in combination with calcium edetate (Ca-EDTA) was
      used to treat experimentally-induced lead toxicity in calves. In 12 calves lead
      toxicity was induced by po administration of 5 mg lead acetate/kg/d until the
      development of overt signs. The calves were divided into 3 groups: untreated
      control; thiamine-treated; and thiamine+Ca-EDTA-treated. The use of 25 mg
      thiamine/kg sc twice daily cured 2/4 calves, whereas 4/4 calves recovered with 25
      mg thiamine+110 mg Ca-EDTA/kg iv twice daily. Lead concentrations in blood and
      tissues were significantly lower and histopathologic lesions were less pronounced
      in the treated calves. Treatment with thiamine+Ca-EDTA was more effective than
      the use of thiamine alone.

PMID- 7571352
TI  - Hemodialysis removal of acyclovir.
AB  - A 59-y-old with a history of chronic renal failure on hemodialysis was diagnosed
      with herpes zoster and begun on 800 mg acyclovir 5 times daily. Two days later
      the patient developed visual hallucinations, ataxia, confusion and memory loss
      along with focal myoclonus, nausea and vomiting. No fever, elevated WBC count or
      significant electrolyte imbalance was found. CT scan of the brain was
      unremarkable. The patient was then dialyzed for presumed acyclovir toxicity. Her
      acyclovir level was later found to have been 3.4 micrograms/ml (normal peak range
      0.4-2 micrograms/ml) prior to dialysis. After 3 h of hemodialysis, her post
      dialysis acyclovir level was 1.9 micrograms/ml. After a second course of
      hemodialysis the next day the patient's mental status improved, and she was
      discharged 5 d later. Due to its low volume of distribution (0.6 L/kg), low
      protein binding (about 15%) and water solubility, acyclovir is an example of the
      ideal drug that can be removed by hemodialysis. About 45% of the total body
      amount can be extracted through a 3-h course of hemodialysis with resultant
      improvement in symptoms.

PMID- 7571353
TI  - Closantel intoxication in a dog.
AB  - A case of overdosage with closantel, a salicynalide derivative, in a dog is
      described. The dog received 6 times the recommended dosage. Closantel induced
      optic neuritis, retinal degeneration, partial deafness, hepatotoxicosis and
      myopathy. Only the blindness was irreversible. The therapy included albumin
      administration to reduce the acute toxicity of closantel.

PMID- 7571354
TI  - Mescalbean (Sophora secundiflora) toxicity in a dog.
AB  - Mescalbean (Sophora secundiflora) toxicity is reported in a dog. Mescalbean
      toxicity causes intolerance to exercise, muscle rigidity and collapse upon
      exercise, with a rapid recovery upon resting in dogs. Mescalbean toxicity is a
      rare cause of the periodic weakness/syncope class of diseases in dogs in areas of
      the habitat of Sophora secundiflora.

PMID- 7571355
TI  - Chelation of organoarsenate with dimercaptosuccinic acid.
AB  - Alkane arsenate herbicides are available commercially, and their acute toxicity
      has been well documented in previous studies. Animal studies have indicated that
      dimercaptosuccinic acid (DMSA) can be used as an oral chelating agent. A 20-y-old
      white male cocaine addict attempted suicide by drinking approximately 500 ml of a
      16% monosodium methanearsenate solution. He vomited 10 or more times and was
      admitted to the intensive care unit with impending shock and early liver and
      renal involvement. Four 5-day courses of 30 mg DMSA/kg/24 h were given. This
      brought the serum arsenic level from 2,871 micrograms/L to 6 micrograms/L, and
      his urine arsenic level from 78,920 micrograms/L to 21 micrograms/L in 30 d.
      Renal function tests returned to normal, with normal renal creatinine clearance,
      normal blood urea nitrogen and serum creatinine. However liver functions were
      abnormal, with elevation of serum transaminases, which later proved secondary to
      chronic hepatitis. No side effects of DMSA was encountered during the therapy.
      DMSA was successfully used to detoxify acute organoarsenate poisoning in a
      clinical setting, supporting experimental reports in the literature.

PMID- 7571356
TI  - Promethazine toxicity in a seven-month-old Doberman pinscher.
AB  - A 7-mo-old female Doberman Pinscher undergoing antibiotic treatment for
      tonsillitis was presented in near collapse with markedly low blood pressure,
      tachycardia, dilatation of pupils (non-responsive to light), and gastrointestinal
      distress. Since the owner could provide no history of significant toxin exposure,
      general supportive and non-specific toxicologic treatment protocols were
      initiated. Within 4 h marked improvement was observed. The owner's wife revealed
      that promethazine suppositories had been administered at a toxic level to control
      the vomition accompanying the tonsillitis.

PMID- 7571357
TI  - Rhabdomyolysis in paraphenylenediamine intoxication.
AB  - Edema of the upper airways and rhabdomyolysis developed in a young patient as a
      consequence of paraphenylenediamine poisoning. Treatment with adrenaline,
      steroids and enforced diuresis prevented tracheostomy and renal failure.

PMID- 7571358
TI  - International Poison Information Center data collection capabilities.
AB  - Hundreds of poison information centers are in operation throughout the world.
      Their common objective is to reduce the morbidity and mortality associated with
      accidental and intentional poisoning exposures. However, there is little
      information available which describes the impact of the centers on the outcome of
      poisonings or on poisoning trends. The objective of this project was to determine
      the data collection capabilities of poison information centers outside of the US
      with a goal of ascertaining whether a common database existed and if an
      international database of poisoning exposures could be developed. A survey was
      developed which requested information on the specific instrument used to document
      poisoning exposures, how that information was compiled, whether it was available
      in a computer database, the type of database, and whether it was available to
      external agencies and at what cost. The survey was sent to 75 poison information
      centers outside of the US. The data were compiled and analyzed using Paradox 3.5.
      Twenty-four of the 75 poison information centers completed and returned the
      surveys. Four of the 24 had no computer capabilities and only 9 centers indicated
      a willingness to share data. The majority of the databases were in a DOS format,
      but no consistent type of database software was used. If the sample that
      responded to the survey is representative of the international poison information
      center community, there is neither a common data collection instrument nor a
      common toxic exposure surveillance system which can be used to identify poisoning
      trends or to track the outcome of poisonings. A concerted effort to create a
      universal database on poisoning exposures should be considered.

PMID- 7571359
TI  - Liver disease in cattle induced by consumption of moldy hay.
AB  - Normally innocuous forages are sporadically associated with hepatogenous
      photosensitization outbreaks at certain times of the year or when grown and
      harvested during unusual environmental conditions, such as periods of excessive
      rainfall. Allegations of livestock illness following consumption of such moldy
      hays are associated with clinical syndromes uncharacteristic of known forage
      related diseases, suggesting that unidentified toxin(s) may be responsible. This
      study was instigated by field observations of hepatogenous photosensitization in
      cattle fed alfalfa-grass forage. To document the toxic nature of the hay, large
      bales of hay (450 kg) were fed, ad libitum, to 3 groups of 2 calves each.
      Elevated serum liver enzymes provided evidence of hepatobiliary disease. Gamma
      glutamyl transferase activities in serums of the calves sustained at least a 10
      fold increase above baseline during the feeding trials. Histologic examination of
      liver biopsies and postmortem sections revealed mild periportal fibrosis and
      biliary hyperplasia. Culture material from 12 fungal isolates from the hay failed
      to induce liver disease in calves.

PMID- 7571360
TI  - Ginger Jake and the blues: a tragic song of poisoning.
AB  - Prohibition, "The Noble Experiment", ushered in speakeasys, gangsters and bathtub
      gin in the 1920s. For many Americans, however, it led to a period of joblessness,
      hard times, and austerity. The story of Jamaican Ginger ("Jake") poisoning, in
      which batches of a cheap, alcoholic tonic were laced with tri-ortho cresyl
      phosphate (TOCP) is one of cynical despicable behavior on the part of those
      responsible and a tragic enduring legacy for the invisible group of Americans who
      were victimized. TOCP, a potent organophosphate, caused an axonal dying-back
      neuropathy affecting mainly large muscle groups. Jake poisoning struck about
      50,000 adults, mostly poor middle-aged vagrants with little medical care or
      social standing. Their symptoms and stories were told not only in medical
      journals but also in song. Hillbilly jazzmen sang of the "Jake Leg Blues" with a
      resignation to the fate of their own undoing, brought on by the intemperance of a
      wasted life. The postscript is grim--those responsible received little
      punishment; many who drank "Jake" were left both uncompensated and crippled by
      irreversible paralysis.

PMID- 7571362
TI  - Non-molecular information transfer from thyroxine to frogs with regard to
      homeopathic toxicology.

PMID- 7571361
TI  - Therapeutic utility, constituents and toxicity of some medicinal plants: a
      review.
AB  - Man has always made use of flora to alleviate suffering and disease. This review
      presents information on the various therapeutic applications of plants used in
      traditional medicine, their active principles and observed side effects in
      animals and human beings. We also focus on the gaps in our knowledge about plant
      toxicoses that require scientific investigations and offer some logical
      conclusions.

PMID- 7571363
TI  - Gene toxin patterns of Escherichia coli isolated from diseased and healthy
      piglets.
AB  - DNA probes specific for genes coding for the heat stable enterotoxins (ST-I and
      ST-II), the heat labile enterotoxins (LT-I and LT-II), Shiga like cytotoxins and
      for the enterohemorrhagic factor (EHF), were used to examined 150 fecal
      Escherichia coli isolates from both diarrheic and healthy piglets. Thirty seven
      percent of the isolates hybridized with the LT-I probe, seventy one of them did
      so with the LT-II probe, while seventy six percent of the isolates possessed
      genes coding for the heat stable enterotoxins. No SLT-I positive hybridization
      was found and four percent of the isolates possessed SLT-II genes.

PMID- 7571364
TI  - The protective efficacy of cloned Moraxella bovis pili in monovalent and
      multivalent vaccine formulations against experimentally induced infectious bovine
      keratoconjunctivitis (IBK).
AB  - Calves were vaccinated with cloned Moraxella bovis pili of serogroup C
      (experiment 1) or B (experiment 2) either as a monovalent formulation or as part
      of a multivalent preparation with pili of six other serogroups. Within 4 weeks of
      the second vaccine dose vaccinated calves and non-vaccinated controls were
      challenged via the ocular route with either virulent M. bovis strain Dal2d
      (serogroup C) or M. bovis strain 3WO7 (serogroup B) in experiments 1 and 2,
      respectively. Calves vaccinated with multivalent vaccines had significantly lower
      antibody titres than those vaccinated with monovalent preparations. Nevertheless,
      the levels of protection against infectious bovine keratoconjunctivitis (IBK)
      achieved with multivalent vaccines were 72% and 83% for the groups challenged
      with M. bovis strains of serogroups B and C, respectively. The serogroup C
      monovalent vaccine gave 100% protection against experimentally induced IBK and M.
      bovis isolates cultured from the eyes 6 days post-challenge were identified as
      belonging solely to serogroup C. Unexpectedly, only 25% protection was achieved
      against homologous strain challenge of calves that received the monovalent
      serogroup B vaccine. Furthermore, the majority of M. bovis isolates recovered
      from calves in this group belonged to serogroup C, as did half of those isolates
      cultured from the multivalent vaccinates. The remaining bacterial isolates from
      the latter group, together with all isolates from the non-vaccinated controls,
      belonged to serogroup B. Results are consistent with the hypothesis that
      derivatives of the serogroup B challenge inoculum had expressed serogroup C pilus
      antigen within 6 days of the challenge, possibly as a result of pilus gene
      inversion occurring in response to the presence of specific antibody in eye
      tissues and tears.

PMID- 7571366
TI  - Properties of a Streptococcus suis isolate of serotype 2 and two capsular
      mutants.
AB  - Encapsulation is thought to be a critical virulence factor of Streptococcus suis.
      In the present study two capsular type 2 mutants of S. suis (M42 and M2) and
      their S. suis parent strain (89-1591) were further characterized. All three
      cultures reacted with group D specific antiserum whereas parent strain 89-1591
      and mutant M42 but not mutant M2 reacted with specific antiserum against capsular
      type 2. Both mutants had higher surface hydrophobicity and showed an increased
      adherence to human epithelial cells and to lung macrophages of rabbits as
      compared to the parent strain. In phagocytosis experiments with polymorphonuclear
      leucocytes the encapsulated parent strain was more resistant to phagocytosis than
      both mutant strains. These findings might help to understand the role of
      encapsulation of S. suis in the process of infection.

PMID- 7571365
TI  - Evaluation of phenotypic and genotypic methods for epidemiological typing of
      Staphylococcus aureus isolates from bovine mastitis in Denmark.
AB  - The value of five different typing methods (antibiogram typing, biotyping, phage
      typing, plasmid profiling and restriction fragment length polymorphism of the
      gene encoding 16S and 23S ribosomal RNA (ribotyping)), in discriminating 105
      Staphylococcus aureus strains from bovine milk samples obtained from 105
      different Danish dairy herds was investigated. A total of 85 strains (81%) proved
      susceptible to all of the 11 antibiotics tested, and the remaining 20 strains
      could be divided into 5 different antibiogram patterns. The predominant
      resistance pattern, penicillin resistance, was observed in 15 (75%) of the 20
      antibiotic resistant strains. Biotyping assigned the strains to 14 different
      types, with the most common type accounting for 25.7% of the strains. Ninety
      eight (93.3%) strains could be typed by phages, assigning them to 19 different
      phage types. The predominant phage type accounted for 31.4% of the strains. Eight
      different plasmid profiles was observed among 24 (23%) strains harbouring
      plasmids. Ribotyping yielded 30 different types, with the most common accounting
      for 29.5% of the strains. The single most discriminatory typing method was
      ribotyping (0.863) followed by biotyping (0.842) and phage typing (0.795).
      Plasmid profiling (0.395) and antibiogram typing (0.327) had low discriminatory
      indices. Correspondence among ribotypes and the presence or absence of plasmids
      were observed, as was some degree of correspondence between ribotype, phage type
      and biotype. In general the correspondence between phage type and ribotype were
      stronger than between biotype and ribotype and between biotype and phage type.
      All combinations of two or more methods led to an improved index of
      discrimination compared to the individual methods indicating, that some
      subdivision of types had taken place. The combination of phage, bio- or
      ribotyping or all three methods in combination are considered to be an efficient
      combination of typing methods for epidemiological investigation of S. aureus
      mastitis.

PMID- 7571367
TI  - Intracellular survival and multiplication of virulent and less virulent strains
      of Streptococcus bovis in pigeon macrophages.
AB  - The intracellular fate of pigeon S. bovis strains ingested by macrophages was
      studied in vivo and in vitro. During in vivo experiments, histological and
      electron microscopical examinations demonstrated numerous cocci, which appeared
      to be actively multiplying, within splenic macrophages of pigeons experimentally
      inoculated with a highly virulent S. bovis serotype 1 strain. In pigeons
      inoculated with a low virulence serotype 3 strain, intracellular cocci were only
      occasionally observed. For in vitro experiments, pigeon peritoneal macrophages
      were inoculated with a S. bovis serotype 1 or serotype 3 strain and incubated.
      Following an initial decrease, an increase in the number of intracellular
      bacteria was observed in tests performed with the S. bovis serotype 1 strain,
      demonstrating intracellular multiplication. Macrophages in these experiments had
      all died after 7 h of incubation, possibly indicating that the intracellular
      replication of S. bovis resulted in the release of substances toxic for
      macrophages. In experiments performed with the S. bovis serotype 3 strain, the
      number of intracellular bacteria continuously decreased, reflecting killing of
      organisms. Significant changes in the number of adhering macrophages in S. bovis
      serotype 3 inoculated cultures were not observed. These results indicate S. bovis
      in pigeons is a facultative intracellular bacterium and intracellular
      multiplication may be involved in virulence.

PMID- 7571369
TI  - Evaluation of a potassium chloride extract of Brucella abortus in an ELISA for
      detecting Brucella antibodies in bulk tank milk samples from cows.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed using as antigen a
      potassium chloride extract of Brucella abortus strain 1119-3 for detecting
      Brucella antibodies in bulk tank samples of cow's milk. Three-hundred-thirty-four
      Milk Ring Test (MRT) suspicions milk samples originating from cattle herds in 13
      states and 106 BRT negative milk samples were analyzed. Fifty-four of 334 MRT
      suspicious milk samples were positive on ELISA; bacteriologic examinations
      revealed B. abortus field strain was isolated from cows in 15 herds, B. abortus
      strain 19 was isolated from cows in 16 herds and serologic suspects were reported
      in 6 of the other 23 herds. Two-hundred-fifty-eight (85.6%) of the 301 MRT
      suspicious samples were negative on ELISA; field investigations and/or serologic
      tests on cattle failed to disclose Brucella infection in these herds. Suspicious
      ELISA reactions were detected in 22 MRT suspicious bulk tank milk samples;
      serologic suspects were reported in 8 of the 22 herds. No false positive ELISA
      reactions were detected in the 106 MRT negative bulk tank milk samples collected
      from dairy herds in 7 states.

PMID- 7571370
TI  - Colorimetric assay using XTT for assessing virulence of avian Pasteurella
      multocida strains.
AB  - A colorimetric assay using sodium 3,3'-[1[(phenylamino)carbonyl]3,4- tetrazolium]
      bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) was adapted to
      quantitate bactericidal activity of chicken macrophage HD 11 cell line against
      five Pasteurella multocida strains and an avirulent transposon insertion mutant.
      The strains used were virulent P1059, and D92, and four avirulent strains
      including a streptomycin resistant mutant of P1059 (P1059 SmR), two live vaccine
      strains namely, the Clemson University (CU) and M9, and a transposon insertion
      mutant PmTn-294. Percentage of bacteria killed by chicken macrophage (HD 11)
      cells was determined by extrapolation from a standard formazan curve derived by
      incubating XTT with known bacterial cell numbers of each strain. The amount of
      formazan as measured by absorption at 450 nm was directly related to the number
      of viable bacterial cells. The percentages of P1059 SmR, CU, M9 and PmTn-294
      killed by HD 11 cells were approximately 50%, 61%, 25% and 34%, respectively. By
      contrast, the virulent P1059 and D92 strains were resistant to killing, and were
      able to replicate inside the HD 11 cells. Association of virulence with
      resistance to phagocytic killing by HD 11 cells as assessed by the colorimetric
      bactericidal assay, was validated with resistance to complement (C')-mediated
      killing and a turkey mortality test. Strains P1059 and D92 were resistant to C'
      mediated killing, whereas strains P1059 SmR, CU, M9 and PmTn-294 strains were
      susceptible. All turkeys challenged with P1059 or D92 were dead within 18 hrs.
      Mortality did not occur in turkeys challenged with strains of P1059 SmR, M9 and
      PmTn-294. The mortality among CU challenged turkeys ranged from 0 to 40%. The
      results suggest that the colorimetric bactericidal assay using XTT can be used to
      quantitate chicken macrophage phagocytic killing of P. multocida strains, and may
      be a valuable assay to differentiate virulent from avirulent strains of avian P.
      multocida.

PMID- 7571371
TI  - Chaotropic agents cause disaggregation and enhanced activity of Pasteurella
      haemolytica leukotoxin.
AB  - Pasteurella haemolytica biotype A, serotype 1 grown to late logarithmic growth
      phase in cell culture medium (RPMI 1640) produced highly aggregated leukotoxin.
      The multimer mass of the highly aggregated leukotoxin in 0.1 M sodium phosphate
      buffer pH 7.0 as determined by gel filtration chromatography on Sephacryl S400HR
      was approximately 8000 kDa. Resuspension of leukotoxin in phosphate buffer
      containing various chaotropic agents resulted in partial disaggregation of
      leukotoxin and enhanced leukotoxic activity. 3M guanidine disaggregated
      leukotoxin to a multimer mass of approximately 800 kDa and enhanced leukotoxic
      activity 3 to 20-fold. In 6 M urea or 1 M sodium thiocyanate, leukotoxin
      multimers were observed ranging in mass from 8000 kDa to 400 kDa, and activity
      enhancement was less than that for leukotoxin in 3 M guanidine. Several
      detergents were tested for enhancement of leukotoxic activity, but only 1% Tween
      20 enhanced leukotoxic activity (4-fold), whereas 1.25% octylglucoside, 10 mM
      CHAPS, and 5 mM deoxycholate diminished and 1% Triton X-100 abolished leukotoxic
      activity.

PMID- 7571372
TI  - Lack of mycobactin dependence of mycobacteria isolated on Middlebrook 7H11 from
      clinical cases of ovine paratuberculosis.
AB  - Mycobacterium avium subsp. paratuberculosis is distinguished from other
      mycobacterial species by its dependence on the iron-chelator factor mycobactin
      and its prolonged incubation period when grown in vitro. Traditionally, a very
      low rate of isolation has been considered characteristic of sheep strains of this
      mycobacterium species. In the present study, a comparison was made of the
      performance of two media, Lowenstein-Jensen and Middlebrook 7H11/OADC both with
      and without mycobactin, on the isolation of M. a. paratuberculosis from ovine
      cases of the disease. A high isolation rate in both media was observed. Moreover,
      our results indicated that mycobactin dependence of sheep strains of M. a.
      paratuberculosis is medium related, being dependent on Lowenstein-Jensen and
      independent on Middlebrook 7H11/OADC.

PMID- 7571373
TI  - In vivo variation of Mycoplasma gallisepticum antigen expression in
      experimentally infected chickens.
AB  - The antigen expression profiles of Mycoplasma gallisepticum isolates obtained
      from tracheal swabs of chickens after aerosol-inoculation with M. gallisepticum
      strain R or clonal variant R/E were examined in western immunoblots. A reference
      anti-M. gallisepticum chicken antiserum and antisera from individual infected
      chickens as well as monoclonal antibodies (mAbs) specific for surface proteins
      were used to monitor in vivo antigenic variation. mAbs 1E5 and 12D8, recognizing
      PvpA and p67a, recently shown to undergo high-frequency in vitro phase variation,
      were used for consecutive staining of colony and western immunoblots in order to
      distinguish between the resultant phenotypes with respect to the corresponding
      epitopes. Marked differences in the expression of major immunogenic proteins,
      including p67a, were observed between the two inocula as well as among reisolates
      recovered at different times of infection. Comparative western immunoblot
      analysis of the rapidly changing chicken serum antibody response and reisolates
      recovered during the course of an experimental infection with M. gallisepticum R
      or clonal variant R/E suggest that immune modulation may have a key role in
      generating surface diversity. In addition, comparison of colony immunoblots of
      strain R inoculum and of reisolated colonies from tracheas of birds 8 days post
      infection indicated an in vivo selection of the PvpA+p67a- phenotype. This study
      established that surface antigens of M. gallisepticum are subjected in vivo to
      rapid alteration in their expression. This variability may function as a crucial
      adaptive mechanism, enabling the organism to escape from the host immune defense
      and to adapt to the changing host environment at different stages of a natural
      infection.

PMID- 7571375
TI  - Pathogenesis of swine vesicular disease after exposure of pigs to an infected
      environment.
AB  - The pathogenesis of swine vesicular disease (SVD) has been studied following a
      natural route of infection. In two experiments groups of ten and eight pigs
      respectively were introduced into a stable contaminated with SVD virus. At
      various intervals after stable exposure, pigs were killed and the amount of virus
      was determined in serum, vesicles (if present), spleen, kidney, and in seven
      lymph glands representing various parts of the body. One day after the pigs were
      introduced into the stable, five out of eight pigs were viraemic and virus could
      be isolated from various tissues. At 2 d after introduction, three out of four
      pigs killed had vesicular lesions on the feet. The tonsils of all pigs killed
      between 1 to 7 d after introduction into the stable were virologically positive.
      Four days after introduction 50% of the pigs were serologically positive and at 7
      d all pigs had developed an antibody response. This study shows that contact with
      a SVD virus contaminated environment can be equally as infectious as injection,
      or direct contact with SVD infected pigs, causing a rapid spread of the disease.
      Because the tonsil was shown to be highly efficient in trapping and growing
      circulating virus, we recommend that in addition to serological examination,
      virus isolation from pig tonsils should be used to study the epidemiology of SVD
      on farms where the infection is present.

PMID- 7571374
TI  - A mutant of pseudorabies virus with deletion of glycoprotein gIII gene prepared
      from a Japanese isolate: it fails to agglutinate mouse erythrocytes.
AB  - A mutant with deletion of the glycoprotein gIII gene was produced from a Japanese
      isolate of pseudorabies virus (PrV) and characterized. Viral titers of the mutant
      propagated in PK-15 cells were always lower than those of the parental virus. The
      parental virus agglutinated BALB/c mouse erythrocytes, whereas the deletion
      mutant showed no hemagglutinating activity. Pigs inoculated with the parental
      virus produced not only neutralizing but also hemagglutination-inhibiting
      antibodies. On the other hand, the mutant induced high titers of neutralizing
      antibody comparable to the parental virus but no hemagglutination-inhibiting
      antibody in inoculated pigs, suggesting that glycoprotein gIII is an essential
      component for hemagglutination of PrV. Finally, no evidence that the deletion
      mutant lost virulence for mice was obtained.

PMID- 7571368
TI  - Selective humoral immune response of Balb/C mice to Brucella abortus proteins
      expressed by vaccinia virus recombinants.
AB  - Genes encoding Brucella abortus Cu/Zn superoxide dismutase (SOD) and a 54 kDa
      Escherichia coli HtrA homologue were cloned into shuttle plasmids pUV-1 and
      pSC11, and transfected into vaccinia virus to develop recombinants vUBSOD and
      vSB54. Control vaccinia virus recombinants vUV-1 and vSC11, carrying only the
      beta-gal reporter gene but no B. abortus DNA were also developed. Recombinants
      were analyzed in Western blotting using a polyclonal B. abortus immune serum.
      vUBSOD expressed a protein of apparent molecular weight of 28 kDa, composed of
      the 20 kDa B. abortus Cu/Zn-SOD and a protein approximately 8 kDa encoded by a
      portion of the vaccinia virus TK gene. vSB54 expressed a 54 kDa protein
      corresponding to the 54 kDa HtrA homologue. Recombinants vUSV-1 and vSC11 did not
      express B. abortus proteins. Groups of mice were inoculated intraperitoneally
      with 10(7) TCID50 of 1 of the 4 different recombinant vaccinia viruses and 5
      weeks later their sera were analyzed for antibodies against vaccinia virus and B.
      abortus proteins. Each group of mice responded with antibodies to vaccinia virus.
      Sera of vSB54-inoculated mice recognized the 54 kDa HtrA homologue. vUBSOD did
      not induce a humoral immune response. These results represent the first report on
      the expression of B. abortus proteins by vaccinia virus recombinants and the
      first demonstrated immune response against a B. abortus protein expressed by such
      a recombinant.

PMID- 7571376
TI  - Effect of heparin on hemagglutination by Akabane and Aino viruses belonging to
      the Simbu group of bunyaviruses.
AB  - Heparin inhibited the hemagglutinin activity of Akabane and Aino viruses. The
      minimal inhibitory concentration of heparin required to inhibit 8
      hemagglutination (HA) U of Akabane and Aino viruses was 10 U/ml. Goose
      erythrocytes failed to combine with the HA inhibitory factor of heparin. On the
      other hand, goose erythrocytes treated with heparinase had greatly reduced
      agglutinability by Akabane virus. Virus-heparin complex formation was observed by
      sedimenting heparin with the virus particles.

PMID- 7571377
TI  - Comparison of serological tests for the diagnosis of feline immunodeficiency
      virus infection of cats.
AB  - A new enzyme-linked-immunosorbent assay (ELISA) for the detection of antibodies
      to feline immunodeficiency virus was compared with previously described ELISAs.
      Serum samples from 184 infected or uninfected cats were tested using a whole
      virus lysate kit and ELISAs based on recognition of one of two synthetic peptides
      (P237 and P253) localized in the transmembrane domain of the viral envelope. The
      whole virus lysate commercial kit led to the detection of 6% false positive and
      4.3% false negative sera. The ELISA based on peptide P253 gave no false positive
      result and failed to detect only one serum that was subsequently shown to be
      positive by radio-immunoprecipitation assay. A sandwich-ELISA test using
      Galanthus nivalis agglutinin, a lectin that specifically binds terminal mannose
      groups of the envelope proteins was used as a confirmatory test for equivocal
      results with peptide ELISA and gave similar results. This study indicates that
      recognition of P253 could serve as a sensitive and specific test for the
      diagnosis of seropositivity to feline immunodeficiency virus, and moreover that
      the Galanthus nivalis ELISA could be useful in equivocal cases as a confirmatory
      test.

PMID- 7571378
TI  - DNA diversity among isolates of Campylobacter jejuni detected by PCR-based RAPD
      fingerprinting.
AB  - A PCR-based randomly amplified polymorphic DNA method was used to amplify
      Campylobacter jejuni DNA using a single oligonucleotide primer derived from
      either a homologous source or from Mycoplasma gallisepticum. The method was able
      to detect the heterogeneity of amplified DNA from human, chicken and turkey
      sources and can be used as a tool to study the epidemiology of Campylobacter
      jejuni infection.

PMID- 7571380
TI  - Chlamydia psittaci infections: a review with emphasis on avian chlamydiosis.
AB  - In the first part of this article the general characteristics of Chlamydia
      psittaci namely the history, taxonomy, morphology, reproductive cycle, metabolism
      and genetics are reviewed. For the taxonomy in particular, a considerable amount
      of new information has become available in recent years, following the
      application of monoclonal antibodies and restriction enzymes. Using these
      techniques isolates of Chlamydia psittaci from birds have been subdivided in
      different serovars, a number of isolates have been classified in a new species
      (Chlamydia pecorum) and isolates from animals have been classified as Chlamydia
      trachomatis. In the second part of the article, the current knowledge on avian
      chlamydiosis is summarized. Emphasis is put on clinical signs, lesions,
      pathogenesis, epizootiology, immunity, diagnosis, prevention and treatment. Also
      the public health considerations are reviewed. It is concluded that the diagnosis
      of avian chlamydiosis is laborious and that there is still a need for more
      accurate, simple and rapid diagnostic tools, both for antigen and antibody
      detection in various species of birds.

PMID- 7571379
TI  - The amino acid requirements of Staphylococcus aureus isolated from cases of
      bovine mastitis.
AB  - The amino acid requirements of seven strains of Staphylococcus aureus isolated
      from cases of bovine mastitis were determined. Arginine, cystine, glycine,
      leucine, proline and valine were essential for the growth of all isolates. In
      addition, all isolates required one or more of the following: glutamic acid,
      histidine, isoleucine, lysine, methionine, phenylalanine, tryptophan and
      tyrosine.

PMID- 7571381
TI  - Contact area and static pressure profile at the plate-bone interface in the
      nonluted and luted bone plate.
AB  - Contact area and pressure between 6-hole broad dynamic compression plates and 20
      pairs of equine third metatarsal bones were measured using nonluted and luted
      plating techniques. Pressure-sensitive film (pressure ranges 10 to 50 MPa and 50
      to 130 MPa) was used as the static pressure transducer. Nonluted and one of two
      luting techniques were tested on each pair of bones; each luting technique was
      tested on 20 bones. Quantitative determinations of contact area and pressure were
      made using computerized image processing techniques. Mean (+/- SD) total contact
      area for nonluted plates was 18.49% +/- 3.5% of the potential plate-bone contact
      area. Luting increased (P < .05) total contact area to 25.56% +/- 4.0% and 31.29%
      +/- 6.6% for the respective luting techniques. The effects of luting on contact
      area were dependent on the contact pressure. At contact pressure ranges 10 to 20
      and 21 to 35 MPa, luting increased contact area. In contact pressure ranges 36 to
      45 and 50 to 65 MPa, plate-bone contact was inherently greatest and plate luting
      had no significant effect on contact area. In contact pressure ranges 66 to 99
      and 100 to 126 MPa, luting decreased contact area. Contact area was increased at
      lower contact pressures at the expense of higher pressure contact. Contact in the
      middle third of the plate was 20% to 40% of the contact at either end of the
      plate. Plate luting increased contact area best where plate-bone contour was most
      similar.

PMID- 7571382
TI  - Evaluation of tissue adhesive to contain axonal regeneration in horses.
AB  - Bilateral palmar and plantar digital neurectomies were completed in 10 horses (a
      total of 80 neurectomies) using one of three methods: (1) simple transection
      (guillotine method); (2) epineural capping; (3) n-butyl cyanoacrylate injected
      into the epineural sheath to act as a nerve sealant. Horses were regularly
      evaluated clinically for tenderness in and around the surgical site, as well as
      skin sensation at the coronary band in the heel region, during the 12-week course
      of the study. None of the surgical sites exhibited any signs of drainage or
      infection. Horses were then euthanatized, the nerve stumps were dissected from
      surrounding tissues, and the length and width of the tissue mass that had formed
      on the end of the nerve was recorded. Longitudinal and transverse sections of the
      nerve endings were examined histologically for numbers of proliferating axon
      sprouts (neuroma formation); whether the axons had penetrated the epineurium;
      degree of Schwann cell proliferation; degree of chronic inflammation; extent of
      foreign body reaction; extent of retrograde degeneration of the nerve bundles;
      and amount of fibrovascular proliferation. The proportion of legs exhibiting
      tenderness or heel sensation did not differ significantly between the three
      different treatments at any of the six different times they were examined. There
      was no difference between the three treatments in the length or width of the
      fibrous tissue scar on the ends of the nerves or in the number of sprouting axons
      from the ends of the nerves. Of 80 nerves examined, only two nerves were not
      confined to the epineurium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571383
TI  - A comparison of medullary thyroid carcinoma and thyroid adenocarcinoma in dogs: a
      retrospective study of 38 cases.
AB  - The medical records of 38 dogs with thyroid neoplasia that were treated by
      surgical excision of the tumor, or had an incisional biopsy performed as a
      diagnostic procedure, were reviewed. Of the 38 dogs, 21 (55%) had resectable
      tumors, whereas 17 (45%) had an incisional biopsy as the tumors were
      nonresectable. All dogs had an initial diagnosis of thyroid carcinoma. The type
      of carcinoma was confirmed in 33 dogs by histological and immunohistochemical
      examination. Twelve dogs (36%) had medullary thyroid carcinoma, and 21 dogs (64%)
      had thyroid adenocarcinoma. Of the 12 dogs with medullary thyroid carcinoma, 10
      (83%) had resectable tumors. Of the 10, three (30%) had at least a 1-year
      survival. None had radiographic evidence of metastasis at the time of surgery. Of
      the 21 dogs with thyroid adenocarcinoma, 11 (52%) had resectable tumors. Of the
      11 dogs, five (45%) had at least a 1-year survival. Three dogs had radiographic
      evidence of metastasis at the time of surgery. Of 10 dogs with nonresectable
      thyroid adenocarcinoma, two dogs (20%) had at least a 1-year survival. In the
      dogs in this study, medullary thyroid carcinoma was more prevalent than
      previously reported. Most of the medullary thyroid carcinomas were well
      circumscribed and resectable. Medullary thyroid carcinoma may possess gross and
      histological characteristics of a less malignant nature when compared with other
      thyroid carcinomas.

PMID- 7571384
TI  - A comparison of simple continuous versus simple interrupted suture patterns for
      tracheal anastomosis after large-segment tracheal resection in dogs.
AB  - Two suture techniques for tracheal anastomosis after large-segment tracheal
      resection were compared. Eight cartilages were resected from the trachea of each
      of 12 dogs; anastomoses with 4-0 polydioxanone suture were created using a simple
      continuous suture technique in six dogs and a simple interrupted suture technique
      in six dogs. Surgical time was shorter but apposition of tracheal segments at the
      time of surgery was less precise with the simple continuous suture technique. The
      dogs were evaluated for 150 days after surgery. Clinical abnormalities after
      tracheal resection and anastomosis were not observed. Percent dorsoventral
      luminal stenosis was calculated by measuring the tracheal lumen diameter on
      lateral cervical radiographs. Percent luminal stenosis was calculated
      planimetrically using a computerized digitizing tablet. Anastomotic stenosis was
      mild in all dogs; however, the mean percent.luminal stenosis determined
      planimetrically was significantly greater for dogs that had the simple continuous
      suture technique. Planimetric measurements of cross-sectional area made before
      and after formalin fixation were not significantly different. Radiographic
      determination of percent dorsoventral luminal stenosis was a poor predictor of
      diminution of cross-sectional area determined planimetrically.

PMID- 7571385
TI  - Long-term results of complete and partial ligation of congenital portosystemic
      shunts in dogs.
AB  - The medical records of 65 dogs that underwent complete or partial ligation of a
      single congenital portosystemic shunt (CPSS) were reviewed to determine the long
      term clinical clinical results. Information retrieved from the records included
      age at surgery, preligation (baseline) portal pressure, postligation portal
      pressure, change in portal pressure from baseline, complete or partial occlusion
      of the shunting vessel and fasting, and 2-hour postprandial bile acids from the
      preoperative, early postoperative (PO), and greater than 1 year PO time periods.
      A clinical rating score derived from a follow-up examination greater than 1 year
      PO was assigned to each dog. Of the 56 dogs that survived the perioperative
      period, 29 (52%) had complete and 27 (48%) had partial ligations. Age at surgery,
      pre- and postligation portal pressure, change in portal pressure from baseline
      and serum bile acid concentrations were not related to long-term clinical
      outcome. Clinical rating scores were significantly greater for dogs with partial
      CPSS ligations compared with dogs with complete ligations, indicating a less
      favorable clinical outcome for partial ligations. Fasting and 2-hour postprandial
      bile acid values at both PO time intervals were significantly greater in partial
      versus complete ligation groups. Follow-up information for more than 1 year was
      available on 18 of 29 dogs (62%) with complete ligations. All were clinically
      normal. Of 27 dogs with partial ligations, 11 dogs (41%) developed recurrence of
      clinical signs resulting in presentation to the university or referring
      veterinarian for additional surgery, medical management, or euthanasia. Only
      three dogs with partial CPSS ligation (11%) were clinically normal.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571386
TI  - The effects of implant orientation, canal fill, and implant fit on femoral strain
      patterns and implant stability during catastrophic testing of a canine cementless
      femoral prosthesis.
AB  - Cementless femoral stems were placed into 12 normal greyhound femora. The
      implanted femora were divided into three groups by stem orientation and implant
      size and loaded in axial compression at a rate of 25 newtons (N) per second until
      failure. Rosette strain gauges were used to measure femoral principal strains at
      500 N, 1,000 N, 1,500 N, and at maximum load. During maximum load, varus
      orientation of the femoral stem had significantly higher tensile hoop strains in
      the proximomedial cortex, whereas neutral orientation had higher tensile hoop
      strains along the cranial cortex. Femoral fractures occurred in these areas of
      peak tensile strain. There was no difference in maximum load between groups,
      therefore varus orientation did not predispose to fracture. Maximizing canal fill
      and implant fit increased implant stability.

PMID- 7571389
TI  - The effects of medetomidine on cardiac contractility in autonomically blocked
      dogs.
AB  - The effects of medetomidine on load-dependent and relatively load-independent
      indices of left ventricular contractility and hemodynamics were studied in 8
      chloralose-anesthetized, autonomic-blocked dogs. Left ventricular contractility
      was assessed by the maximum rate of increase in pressure (dP/dtmax), the slope of
      the end-systolic pressure volume relationship (Ees), preload recruitable stroke
      work (PRSW), and dP/dtmax-end-diastolic volume relation (SdPV). Dogs received 5
      or 10 micrograms/kg of medetomidine IV. The dP/dtmax decreased significantly 30
      minutes after both doses of medetomidine. The Ees did not change. Both SdPV and
      PRSW increased 5 minutes after both doses of medetomidine. Mean arterial
      pressure, left-ventricular end-diastolic and end-systolic pressures, peripheral
      vascular resistance and effective arterial elastance increased 5 minutes after
      both doses of medetomidine. Stroke volume, cardiac output, and stroke work
      decreased 5 minutes after medetomidine administration. End-diastolic volume did
      not change. End-systolic volume increased but the difference was not significant.
      Our study suggests that medetomidine increases inotropy and vascular resistance
      in autonomic-blocked dogs and that both ventricular and vascular responses to
      pharmacological manipulation must be considered for a complete assessment of the
      inotropic effects of a drug.

PMID- 7571387
TI  - Cephalothin and cefazolin in vitro antibacterial activity and pharmacokinetics in
      dogs.
AB  - The periods of time that cephalothin and cefazolin serum concentration remained
      above minimum inhibitory concentration (MIC) for beta hemolytic, coagulase
      positive staphylococcal, and Escherichia coli clinical isolates were compared.
      Cephalothin and cefazolin were similarly very effective in vitro against
      staphylococcal isolates, with an MIC90 of 0.12 microgram/mL and 0.25
      microgram/mL, respectively. In contrast, cefazolin was more effective than
      cephalothin against E coli isolates; the cefazolin MIC90 for E coli was 16
      micrograms/mL and for cephalothin 64 micrograms/mL. Cefazolin (20 mg/kg
      intravenously [i.v.]) serum concentration remained more than MIC90 for E coli
      isolates significantly longer than serum concentration of cephalothin (40 mg/kg
      i.v.) (P < .001).

PMID- 7571388
TI  - Modification of a nonrebreathing circuit adapter to prevent barotrauma in
      anesthetized patients.
AB  - Barotrauma, pneumothorax, and pneumomediastinum occurred in two anesthetized cats
      in which the waste gas outlet of a nonrebreathing circuit was occluded. To
      prevent any similar cases of barotrauma, we have modified our nonrebreathing
      circuit adapters by inserting a 15 cm H2O PEEP valve into the gas pathway of the
      nonrebreathing circuit adapter. This PEEP valve prevents the circuit and airway
      pressures from exceeding 15 cm H2O if the pop-off valve of the nonrebreathing
      circuit adapter is inadvertently left closed.

PMID- 7571390
TI  - The distribution of invA, pagC and spvC genes among Salmonella isolates from
      animals.
AB  - New molecular diagnostic techniques often rely on hybridization or amplification
      of specific DNA regions to detect pathogenic bacteria. The choice of genes to be
      used as probes or as the targets of amplification techniques is critical to the
      success of these procedures. The genes so used might best be those associated
      with virulent isolates and having a wide distribution among such isolates. In
      this study three genes, invA, pagC and spvC, thought to be associated with the
      virulence of salmonellae, were labelled and used to probe the total DNA from 103
      Salmonella isolates from animals in an attempt to determine whether these genes
      might be useful in diagnostic procedures. pagC was detected in 99% of the
      Salmonella tested, and invA was detected in 94.2% of the isolates. Both pagC and
      invA were detected with a significantly higher frequency than spvC in isolates
      from chickens and swine, but no significant difference in detection of these
      three genes occurred when bovine isolates were examined. Failure to detect any of
      these genes occurred in only one isolate. Isolates from apparently healthy or
      from clinically ill chickens and swine could not be distinguished by detecting
      these three genes. The genes were not detected in the non-Salmonella strains
      tested. These results suggest that, of these three genes, pagC may be the best
      choice for use as a probe or polymerase chain reaction target in future detection
      protocols.

PMID- 7571391
TI  - Training-induced modifications in some biochemical defences against free radicals
      in equine erythrocytes.
AB  - Oxidative stress develops when the generation of free radicals exceeds the
      antioxidant capacity of cells or extracellular fluids. It can also occur as a
      result of physical exercise, and the pathogenesis of exercise-induced myopathies
      and haemolysis in horses may be related to changes in lipid peroxidation caused
      by free radicals. Cells have developed biochemical protection against oxidative
      stress and, as tissues seem to increase their antioxidant defences under chronic
      activation, training may be one of the ways of increasing antioxidant defences.
      Accordingly, we tested some enzymatic antioxidant activities as well as
      nonenzymatic antioxidants in horses undergoing special training. The results
      indicated a decrease in both chemical and biochemical defences against free
      radicals during training. It was deduced that the horses' diet may have been
      unable to provide the increased need for antioxidant defences resulting from
      training.

PMID- 7571394
TI  - Effect of a single dry season anthelmintic treatment of N'Dama cattle on communal
      pastures in The Gambia.
AB  - The effect of a single anthelmintic treatment of cattle during the early dry
      season was studied. One hundred and sixty-six N'Dama cattle, 1-3 years old, were
      selected from five herds. There were 65 males and 101 females divided into two
      groups of 83 animals each. One group was treated with fenbendazole at 7.5 mg/kg
      body weight by mouth in November 1992; the other group remained as the untreated
      control. At monthly intervals from November 1992 to April 1993, each animal was
      weighed and the number of eggs/g of faeces (epg) was determined. The infective
      larvae (L3) were examined following culture of pooled samples from each group of
      animals. In April 1993, 6 animals (3 treated and 3 controls) from the herds under
      study were necropsied. The difference in the weight gains (4.6 kg) of the two
      groups was highly significant (p < 0.0001). The difference in the weight gains
      and the epg between the treated and control groups was influenced by the age of
      the animals. Of the treated animals, one contained no nematodes, one contained
      only 25 Oesophagostomum radiatum, and the third contained 25 Cooperia L4. The
      three untreated animals were all infected. It was concluded that the treatment in
      early dry season, with an anthelmintic effective against both adults and larvae,
      led to a significant reduction in egg counts, to elimination of adults and
      hypobiotic larvae and, consequently, to an increase in the body weight gain by
      the treated animals.

PMID- 7571392
TI  - Plasma hormones and metabolites in cattle in relation to breed (Belgian Blue vs
      Holstein) and conformation (double-muscled vs dual-purpose type).
AB  - Four Belgian Blue double-muscled type (BBDM) bulls, four Belgian Blue dual
      purpose type (BBDP) bulls and four Holstein bulls were used in a fattening trial
      in order to relate differences in the extent of muscle development and adiposity
      to differences in digestibility, endocrine status, protein and lipid metabolism.
      The larger muscle development in BBDM animals was associated with a trend to
      higher nitrogen retention, higher food conversion efficiency (p < 0.05) and lower
      apparent digestibility (p < 0.05). No difference was found between the groups for
      plasma glucose concentration. Higher creatinine, lower alpha-amino nitrogen,
      lower triglycerides and higher non-esterified fatty acid plasma levels were
      observed in BBDM as compared to Holstein bulls (p < 0.05), the BBDP group being
      intermediate. A trend to a higher cholesterol plasma level was found in BBDM
      animals. There was no difference between the three groups in plasma fatty acid
      composition, except for the C14:0 content. Some of the differences in plasma
      metabolites were related to carcass composition and endocrine regulation, a
      decrease in muscle development and an increase in adiposity being associated with
      lower growth hormone production (p < 0.05) and higher insulin (p < 0.05) and IGF
      secretions. The insulin/growth hormone ratio at the end of the fattening period
      was 0.0011, 0.0018 and 0.0069 in BBDM, BBDP and Holstein bulls, respectively, and
      was directly associated with fat deposition.

PMID- 7571393
TI  - The concentration of ionized magnesium in serum during the periparturient period
      of non-paretic dairy cows.
AB  - Ion-selective electrodes have recently been designed for determining the ionized
      concentration of magnesium (Mg2+) in serum. This development may allow new
      insights into some metabolic diseases of cattle. For this report, the
      concentrations of Mg2+, total magnesium (Mgtot), ionized calcium (Ca2+), total
      calcium (Catot), and inorganic phosphate (P(i)) were determined in sera from
      seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows
      during the periparturient period. In each animal, a transient increase of Mg2+
      and Mgtot serum concentrations was observed in association with the transient
      decrease in serum concentrations of Ca2+, Catot and P(i) after parturition. On
      average, throughout the study, the serum Mg2+ concentrations were 68.5% of those
      of Mgtot, whereas the serum Ca2+ concentrations were 52% of those of Catot. The
      possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum
      concentrations are discussed.

PMID- 7571395
TI  - Plasma concentrations and tissue residues of bicozamycin given orally to pigs.
AB  - Bicozamycin was dissolved in water and administered to pigs by stomach tube at 40
      mg/kg once daily for 7 consecutive days. The plasma concentration was determined
      on days 1 and 7 of the dosing period. The mean (+/- SD) peak plasma
      concentrations were 2.06 +/- 0.36 micrograms/ml at 3.08 +/- 0.80 h on day 1 and
      2.36 +/- 1.32 micrograms/ml at 2.80 +/- 0.74 h on day 7, the elimination half
      lives being 3.80 +/- 0.92 h and 2.43 +/- 1.41 h, respectively. The mean areas
      under the plasma concentration-time curves were 15.88 +/- 2.18 (micrograms h)/ml
      on day 1 and 12.31 +/- 6.98 (micrograms h)/ml on day 7. These pharmacokinetic
      parameters did not differ between days 1 and 7, suggesting that there was no
      accumulation in the plasma after consecutive oral dosing. The residues in kidney,
      liver and muscle were examined in pigs slaughtered on days 1, 3 and 5 after the
      last dosing. One day after withdrawal, residues were found in the kidneys of all
      three pigs examined, at a mean concentration of 0.26 microgram/g, and in muscle
      from one pig, but not in liver from any of the pigs. Bicozamycin was not detected
      in any of the samples taken 3 or 5 days after withdrawal.

PMID- 7571396
TI  - The influence of ageing on muscarinic receptors, beta-adrenoceptors and adenylate
      cyclase activity in the bovine lung.
AB  - Muscarinic and beta-adrenoceptors were identified in airway epithelium, smooth
      muscle and lung parenchyma from Holstein-Friesian calves and cows and were
      characterized with [3H]quinuclidinyl benzilate and [3H]dihydroalprenolol,
      respectively. The muscarinic receptor density in the smooth muscle of cows (Bmax
      = 4803 +/- 245 fmol/mg protein) was 33% greater (p < 0.01) than in calves. Low
      receptor numbers were detected in the epithelium and parenchyma. In both calves
      and cows, the density of epithelial beta-adrenoceptors was twice as high as in
      smooth muscle and parenchyma. The quantity of beta-adrenoceptors in the tracheal
      epithelium (Bmax = 994 +/- 83 fmol/mg protein) and smooth muscle (Bmax = 492 +/-
      41 fmol/mg protein) in cows was respectively 37% (p < 0.001) and 35% (p < 0.01)
      lower than in calves. Adenylate cyclase (AC) assays indicated that the basal and
      the (-)-isopropylnoradrenaline- (ISO-) stimulated cAMP production were not
      significantly different between the calves and cows. After stimulation with NaF,
      significantly higher cAMP production was found in all tissues from cows.
      Significant correlations were found between absolute AC responses to NaF and beta
      adrenoceptor density in epithelium (r = -0.75, p < 0.001) and smooth muscle (r = 
      0.63, p < 0.01). It seems that, in older animals, the production of cAMP is
      independent of the number of receptors, indicating the presence of fully active
      compensatory mechanisms.

PMID- 7571398
TI  - Human papillomavirus type 11 transcripts are present at low abundance in latently
      infected respiratory tissues.
AB  - Respiratory tract tissues containing latent human papillomavirus (HPV) 11 were
      analyzed by reverse transcription-polymerase chain reaction for the presence of
      viral-specific RNA from the early region of the genome and compared to a similar
      analysis of laryngeal papillomas. Latently infected tissue contained low
      abundance transcripts that could code for E1 and E2 proteins, but lacked evidence
      of spliced transcripts for the E6 and E7 proteins. Both latently infected tissue
      and papilloma tissue contained low-abundance antisense transcripts. Cultured
      cells infected with HPV 11 virions or transfected with HPV DNA, and cells derived
      from latently infected tissue, expressed transcripts similar to those seen in
      papillomas, but at a lower abundance. We postulate that latency is determined by
      the absence of or limiting levels of critical viral proteins.

PMID- 7571399
TI  - Biochemical characterization and localization of JC virus large T antigen
      phosphorylation domains.
AB  - Large T antigen (T Ag), the major regulatory protein produced by the primate
      polyomaviruses, is a multifunctional phosphoprotein expressed early in the viral
      life cycle. T Ag performs many functions essential to viral DNA replication, and
      studies with SV40 T Ag indicate that the regulation of these functions is
      modulated, in part, by the phosphorylation status of this oncoprotein. In this
      study, we demonstrate that JC virus (JCV) T Ag obtained from lytically infected
      and transformed cells is phosphorylated at serine and threonine residues.
      Analysis of JCV T Ag via two-dimensional tryptic peptide mapping generates 14
      phosphopeptides. Additional mapping studies of intact, hybrid, mutant, and
      truncated forms of JCV T Ag have aided the localization of phosphorylation sites
      to the N- or C-terminal region of the protein; both serine and threonine residues
      are modified at each terminus. The data indicate that, unlike the corresponding
      regulatory phosphorylation site Ser677 in SV40, Thr664 is not phosphorylated in
      JCV T Ag. The phosphorylation sites utilized for JCV T Ag, and the regulatory
      role of these sites, are predicted to contribute to the unique biology of this
      human virus.

PMID- 7571400
TI  - Cell clones cured of persistent poliovirus infection display selective
      permissivity to the wild-type poliovirus strain Mahoney and partial resistance to
      the attenuated Sabin 1 strain and Mahoney mutants.
AB  - We report the isolation and characterization of HEp-2c cell clones obtained after
      two successive persistent poliovirus (PV) infections. Once cured, some of the
      cell clones displayed selective permissivity toward the wild-type Mahoney strain
      and partial resistance to particular mutants of this strain, including the Sabin
      1 strain. Two cell clones, CI 4 and CI 10, were studied in greater detail. The
      cytopathic effects of Mahoney infection were comparable in the cell clones and in
      HEp-2c cells. The cytopathic effects of infection by Sabin 1 or Mahoney mutants
      were greatly delayed in CI 4 and CI 10. In the genomic region encoding the capsid
      proteins, determinants involved in the resistance of the cell clones to the
      Mahoney mutants were localized in the amino-terminal part of VP1 (amino acids 22
      and 43), the B-C loop of VP1 (amino acids 94-102), and the loop of VP3 connecting
      its amino-terminal to beta strand B (amino acid 60). These genomic regions are
      thought to be involved in the early steps of viral infection. Virus adsorption
      was slower and less efficient on CI 10 cells than on parental HEp-2c cells. Virus
      adsorption was faster on CI 4 than on HEp-2c cells, and at least as efficient,
      but there was less receptor-induced structural modification of the capsid, a step
      that is required for decapsidation. Furthermore, infection of CI 4 by a Mahoney
      mutant in which the B-C loop of VP1 has been deleted was affected in the later
      steps of infection. These results indicate that, in cells cured of persistent PV
      infection, poliovirus multiplication was restricted at several stages and
      particularly at two steps of virus entry: adsorption and/or the uncoating
      transitions following adsorption onto the receptor.

PMID- 7571401
TI  - Inhibition of replication of avian influenza viruses by the neuraminidase
      inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid.
AB  - The sialidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic
      acid (4-guanidino-Neu5Ac2en), designed with computer assistance and knowledge of
      the crystal structure of influenza virus neuraminidase, has shown antiviral
      effects in animal models of human influenza (M. von Itzstein et al., Nature, 363,
      418-423, 1993). Here we demonstrate that the compound efficiently inhibits the
      enzyme activity of all nine subtypes of avian influenza A neuraminidase in vitro.
      When administered intranasally to chickens infected with lethal viruses, high
      doses of the compound (1000 micrograms/kg) protected 85% of birds harboring
      A/Chick/Victoria/1/85 (H7N7), a fowl plague virus, but not chickens infected with
      other highly virulent viruses of the N1, N2, or N3 subtype. This differential
      inhibitory effect was also seen in a plaque reduction assay with Madin-Darby
      canine kidney cells (MDCK), where 4-guanidino-Neu5Ac2en was more effective
      against A/Chick/Vic/85 (H7N7) than A/FPV/Rostock/34 (H7N1). In contrast to the
      substantial plaque reduction observed in MDCK cells, the drug failed to inhibit
      plaque formation in chicken embryo fibroblasts infected with either
      A/Chick/Vic/85 or A/FPV/Rostock/34, regardless of its concentration. The
      different levels of drug efficacy seen in two cell systems most likely reflect
      the location of virus budding and release in polarized versus nonpolarized cells,
      as well as the compound's mode of extracellular action.

PMID- 7571397
TI  - Reflections on scrapie and related disorders, with consideration of the
      possibility of a viral aetiology.
AB  - The transmissible spongiform encephalopathies of domesticated animals, scrapie in
      sheep and bovine spongiform encephalopathy (BSE), and transmissible mink
      encephalopathy are more than a scientific curiosity; under certain circumstances
      their impact on commercial activities can be calamitous. Knowledge of their
      causation and pathogenesis is still rudimentary, but many consider than an
      unconventional agent, the prion (a brain protein, PrP), that is not associated
      with nucleic acid is involved in both. Others believe that conventional viruses,
      which replicate by virtue of their nucleic acid-defined genes, are involved in
      the causation and progression of the encephalopathies but that technical problems
      have prevented their identification. Others postulate even more exotic causative
      agents. While this paper will particularly address the possibility of a viral
      aetiology for these diseases, it is also emphasized that our knowledge of the
      state of the immune system in animals with encephalopathy needs broadening. There
      are remarkable gaps in our knowledge of the histopathology of these diseases,
      particularly the nature of the characteristic vacuoles. Much further work is
      needed on the biochemical changes in the brain and the serum, particularly of the
      latter as it could lead to an additional means of recognizing clinical cases
      without waiting for the animal to die with subsequent examination of the brain
      for characteristic lesions and the presence of protease-K-resistant PrP.

PMID- 7571402
TI  - Functional analysis of HIV-1 Vpr: identification of determinants essential for
      subcellular localization.
AB  - Vpr is a conserved HIV-1 auxiliary protein that localizes to the nuclear region
      of cells. Vpr is also present in virions, and it is directed into the assembling
      virus when coexpressed with Gag. Each of these two localization activities may be
      important for Vpr function, and we recently identified regions of Vpr that are
      critical for virion incorporation. In this study we analyzed the Vpr domains
      involved in subcellular localization. Immunofluorescence staining of transfected
      cells showed that wild-type Vpr localized exclusively to the nuclear region.
      Mutations in the N-terminal domain that were designed to disrupt a predicted
      alpha-helical structure resulted in aberrant localization, while conservative
      substitutions showed a wild-type pattern. A region in the central portion of the
      protein also has the potential for helical structure, and mutagenesis of two
      conserved amino acids in this domain (A59, H71) impaired localization, while
      substitution of a third (Q65) did not. In contrast, neither the conserved Gly and
      Cys at positions 75-76 nor the C-terminal basic residues (R87, K95) were
      necessary for nuclear localization. In addition, two-residue insertions within
      and between the two putative helices disrupted localization but insertion in the
      C-terminal region did not. Thus, Vpr's subcellular localization function depends
      on the two putative helical domains but is independent of the conserved Gly-Cys
      motif and of specific C-terminal basic residues.

PMID- 7571403
TI  - Suppression of influenza virus infection by an N-thioacetylneuraminic acid
      acrylamide copolymer resistant to neuraminidase.
AB  - We have previously shown that alpha-2-O-methyl-5-N-thioacetylneuraminic acid
      (alpha-Neu5thioAc2Me) has a higher affinity to bromelain-treated hemagglutinin
      (HA) of influenza A virus than sialic acid from natural sources (Machytka et al.,
      1993, FEBS Lett. 334, 117-120). We have now compared the inhibitory effects of
      alpha-Neu5thioAc2Me and other sialic acid analogs on receptor binding and plaque
      formation of intact influenza A viruses. When alpha-Neu5thioAc2Me was polymerized
      by conjugation to polyacrylamide, its affinity to HA increased 10(3)-fold. When
      analyzed by plaque reduction, the alpha-Neu5thioAc2 polymer was about 10 times
      more efficient as an inhibitor of virus replication than the alpha-Neu5Ac2
      polymer, stressing the importance of sulfur at C5. The S-glycoside alpha-2-S
      methyl-5-N-thioacetylneuraminic acid (alpha-Neu5thioAc2SMe) had the same affinity
      to HA as alpha-Neu5thioAc2Me, but was resistant to neuraminidase. The alpha
      Neu5thioAc2S polymer interfered with the replication of a wider spectrum of
      influenza A virus subtypes than the alpha-Neu5thioAc2 polymer. The results
      indicate that the alpha-Neu5thioAc2S polymer has the potential to be used as an
      inhibitor of influenza virus infection.

PMID- 7571404
TI  - Different peptides from hemorrhagic septicemia rhabdoviral proteins stimulate
      leucocyte proliferation with individual fish variation.
AB  - Trout leucocytes from most of the survivors of viral hemorrhagic septicemia virus
      (VHSV) infections were capable of in vitro proliferation (T-like response) when
      cultured in the presence of short synthetic peptides designed from the G and the
      N cDNA-derived protein sequences of VHSV, a virus with substantial economic
      impact in trout farms. In contrast, no significant proliferative responses were
      obtained for the above-mentioned peptides from leucocytes obtained from either
      noninfected or genetically VHSV-resistant trout. However, since the anamnestic
      recognition of particular peptides (epitopes) of the G and the N protein by trout
      leucocytes varies largely within the outbred trout population, larger VHSV
      protein fragments were also tested. The finding that recombinant G and N
      fragments carrying multiple epitopes are recognized by the majority of the
      individual trout surviving VHSV infections and with higher stimulation indexes
      suggests that the recombinant viral proteins could be used as vaccines given the
      outbred nature of the fish.

PMID- 7571405
TI  - A model for mixed virus disease: co-infection with Moloney murine leukemia virus
      potentiates runting induced by polyomavirus (A2 strain) in Balb/c and NIH Swiss
      mice.
AB  - Polyomavirus was originally isolated by Ludwick Gross from a mixture that also
      contained a murine retrovirus. A possible pathogenic interaction between
      polyomavirus and an endogenous mouse retrovirus locus (mtv-7) in polyomavirus
      induced cancer has also been reported. To study potential interactive effects of
      polyomavirus (Py) and Moloney murine leukemia retrovirus (M-MuLV), newborn Balb/c
      and NIH Swiss mice were infected with high titer wild-type Py (A2 strain) and M
      MuLV. Dramatically stunted growth (runting) occurred in 100% of the doubly
      inoculated mice, while much lower frequency of runting occurred in animals
      infected with Py alone and not at all with M-MuLV-infected mice. In situ
      hybridization for Py DNA showed ongoing Py replication and inflammation in
      kidneys (atypical of most mice singly infected by Py) of runted doubly inoculated
      mice. In addition, high Py viral replication continued well past the usual acute
      stage termination. M-MuLV replication was also initially inhibited in bone marrow
      by simultaneous Py infection. No M-MuLV replication was seen in singly or doubly
      infected mouse kidneys. Runting was very rapid, observable within 2 days after co
      infection, arguing against an adaptive or antigen-specific immunological
      mechanism. One possibility was that a cytokine-driven acute response mechanism
      was involved. Supporting this view, RNAse protection assays for various cytokine
      RNAs showed that several were specifically elevated in kidneys of doubly infected
      mice. Three patterns were observed: (1) IL-6 was elevated in doubly infected mice
      early after infection (7 days), but it declined at later times (19 days); (2) IFN
      gamma, IL-1 beta, and IL-10 were elevated at both early and late times; and (3)
      TNF-alpha, IL-12p40, and possibly TNF-beta were elevated only at late times.
      While the cytokines in the third category might be indicative of infiltrating
      inflammatory cells, it seems possible that cytokines in the first or second
      categories might be involved in establishing runting and ongoing polyoma DNA
      replication in the doubly infected mice.

PMID- 7571408
TI  - Cellular immune response of rhesus monkeys infected with a partially attenuated
      nef deletion mutant of the simian immunodeficiency virus.
AB  - To date the vaccines most successful in the simian immunodeficiency virus (SIV)
      model of AIDS are live attenuated viruses. However, the virus-specific immune
      response induced after infection of monkeys with attenuated SIV has not been
      described comprehensively. Therefore, we investigated the cellular immune
      response of eight rhesus macaques infected with a nef deletion mutant of
      SIVmac32H (pC8). In contrast to monkeys infected with pathogenic SIV, pC8
      infected macaques developed a virus-specific T-cell proliferation. In addition,
      all animals showed a proliferative T-cell response to recall antigen and
      mitogens. In six of eight monkeys virus-specific cytotoxic T-cells directed
      against different SIV polypeptides were detected. In two animals, however, the
      truncated nef gene reverted to full length 12 weeks after pC8 infection. These
      two monkeys developed hematological alterations, indicating an immunodeficiency.
      Simultaneously with the onset of disease the animals lost their T-cell
      responsiveness against recall antigens. Eight weeks later their T-cell reactivity
      against mitogens was also abrogated. The results indicate that live attenuated
      SIV induced a virus-specific cellular immune response in monkeys which might be
      associated with the previously reported resistance to superinfection with
      pathogenic SIV. Paradoxically, if the attenuated SIV reverts in vivo to a more
      virulent virus, the SIV-specific immune response was inefficient to prevent the
      onset of immunodeficiency in the animals.

PMID- 7571409
TI  - The role of individual oligosaccharide chains in the activities of the HN
      glycoprotein of Newcastle disease virus.
AB  - To explore the role of N-linked carbohydrate in the activities of the
      hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus (NDV),
      the six glycosylation addition sites (G1-G6) in the HN sequence of the AV strain
      of NDV were mutated. Migration of mutant protein on polyacrylamide gels as well
      as endoglycosidase H digestion of mutant protein showed that four of the addition
      sites (G1, G2, G3, and G4 at amino acids 119, 341, 433, and 481, respectively)
      are used while two (G5 and G6 at amino acids 508 and 538, respectively) are not
      used. Proteins expressed from single and all possible combinations of double and
      triple mutant DNAs as well as the unglycosylated molecule were characterized for
      the presence of specific antigenic sites, formation of disulfide-linked dimers,
      stability, transport to the cell surface, and biological activity. Results showed
      that glycosylation at positions G1 and G2 play little detectable role in the
      folding, stability, or transport of the molecule either singly or in combination
      with other mutations. Mutation of these sequons, however, significantly increased
      the cell attachment and fusion promotion activities of the protein, particularly
      in combination. Mutation of the glycosylation site at G4 either singly or in
      combination with other site-eliminating mutants inhibited the formation of the
      mature protein, while a mutation eliminating the addition site at G3 had a slight
      effect on the efficiency of folding, particularly in combination with mutation of
      the site G4. When normalized to surface expression, elimination of carbohydrate
      addition sites at G3 and G4 singly or in combination with other mutations
      depressed in particular the neuraminidase activity of the protein but not the
      fusion promotion activity. Thus two oligosaccharides do not have a detectable
      role in maturation but do modulate the biological activities of the protein. The
      other two oligosaccharides influence both folding and activity of the protein.

PMID- 7571406
TI  - Biological characterization and molecular cloning of murine C-type retroviruses
      derived from the TSZ complex from mainland China.
AB  - Characterization of the SRS murine retrovirus complex, derived from the TSZ
      system of murine leukemia developed in China, was carried out. The initial stock
      contained XC+, NB-tropic virus (and possibly other viruses), and induced several
      neoplastic diseases in neonatally inoculated NIH Swiss mice: erythroid leukemia,
      myeloid leukemia (acute myeloblastic leukemia), and lymphoblastic lymphoma (both
      B- and T-lymphoid). In addition, approximately 30% of inoculated animals
      developed central nervous system disease--hindlimb paralysis or semilateral
      paralysis. Rescue of virus from the spleen of an animal with combined
      erythroid/myeloid leukemia, followed by endpoint dilution gave two stocks: 19-6
      (XC+, NB-tropic) and 19-7 (XC-, NB-tropic). Both stocks induced erythroid and
      myeloid leukemia, and 19-6 induced CNS symptoms as well. Southern blot analysis
      indicated that the predominant viruses from the 19-6 and the 19-7 cultures were
      related, but different in the env region. An infectious virus molecular clone of
      provirus from 19-6 cells was obtained. The resulting cloned virus [SRS 19-6
      murine leukemia virus (MuLV)] induced four kinds of leukemia: erythroid, myeloid,
      B-lymphoma, and T-lymphoma; in many cases, more than one tumor type was
      identified in the same animal. Such a broad spectrum of leukemias induced by a
      cloned MuLV is unusual. Flaccid hindlimb paralysis induced by SRS 19-6 MuLV could
      be attributed to meningeal B-lymphoma. Immunofluorescent staining with a panel of
      env-specific monoclonal antibodies confirmed that the 19-6 and 19-7 viral stocks
      contained different viruses, which differed from previously characterized MuLVs.
      The viruses of the SRS complex may provide interesting reagents for
      investigations of MuLV-induced disease.

PMID- 7571411
TI  - The influenza virus NS1 protein forms multimers in vitro and in vivo.
AB  - The NS1 protein of the influenza A virus inhibits both the nuclear export of mRNA
      and pre-mRNA splicing. Two functional domains, an RNA-binding domain and an
      effector domain, have been identified in this protein. Here we demonstrate that
      the NS1 protein exists as a dimer in vitro both in the absence of its RNA target
      and when it is bound to a specific RNA target, U6 snRNA. This indicates that it
      is most likely the dimer that binds to the RNA target. Mutational analysis
      indicated that the RNA-binding and dimerization domains are coincident.
      Multimerization also occurs in vivo, as assayed using the yeast two-hybrid
      system. In contrast to the situation in vitro, multimerization in vivo was
      mediated by not only the RNA-binding domain but also the effector domain. This
      suggests that multimerization in vivo involves a cellular protein cofactor that
      bridges more than one NS1 protein molecule together via their effector domains.

PMID- 7571410
TI  - Effects of antibody to the influenza A virus M2 protein on M2 surface expression
      and virus assembly.
AB  - We have investigated the effect of a monoclonal antibody on influenza virus
      release and the cell surface expression of M2, comparing virus strains which were
      observed previously to be sensitive (A/Udorn) or resistant (A/WSN and A/Udorn
      variants) to growth inhibition by M2 antibody 14C2. Incubation of A/Udorn virus
      infected cells in the presence of the inhibitory M2 antibody resulted in a
      significant reduction in the yield of virus, as measured by infectivity assays as
      well as by the release of purified virions. The release of A/Udorn virus was not
      inhibited by the presence of monovalent 14C2 Fab, in contrast to IgG, indicating
      that a bivalent structure is essential for 14C2 antibody-mediated viral growth
      restriction. The level of M2 surface expression in A/Udorn virus-infected MDCK
      cells was found to be reduced to approximately 60% of control levels in cells
      incubated with the 14C2 antibody. In contrast, M2 surface expression levels in
      A/WSN virus-infected cells were decreased by only approximately 5-15%, and A/WSN
      virus assembly appeared to be unaffected by the M2 antibody treatment. M2 antigen
      associated with cell membranes and virus particles was redistributed into
      clusters after M2 antibody treatment in infected cells. Incubation in the
      presence of the 14C2 antibody also reduced M2 surface expression by approximately
      40-50% in cells infected with a recombinant vaccinia virus that expresses the M2
      A/Udorn protein. These results demonstrate that M2 antibody reduces the level of
      influenza virus particle formation in a single cycle of infection and suggest
      that inhibition of A/Udorn virus replication by the 14C2 antibody is related to
      the reduced cell surface expression and redistribution of the M2 protein induced
      by the antibody treatment.

PMID- 7571412
TI  - Dansylcadaverine and cytochalasin D enhance rotavirus infection of murine L
      cells.
AB  - Although murine L cells bind and internalize rotavirus as well as permissive cell
      lines, L cells are essentially nonpermissive for rotaviruses. In nonpermissive
      cell lines such as L cells, internalized rotavirus fails to uncoat and remains as
      infectious, double-shelled particles. This block in the infectious cycle can be
      overcome by direct lipofection of viral particles into the L cell cytoplasm. We
      hypothesized that the internalized rotavirus particles within L cells are
      sequestered in the endocytic pathway and are unable to initiate infection. L
      cells were pretreated with a variety of inhibitors of endocytosis prior to
      infection with rhesus rotavirus. While agents which inhibit acidification of
      endosomes had no effect on rotavirus infection, two potential direct inhibitors
      of vesicular transport, dansylcadaverine and cytochalasin D, enhanced rotavirus
      infection of L cells 5- to 10-fold. All of the drugs, including both inhibitors
      of endocytosis and lysosomotrophic agents, significantly reduced infection of L
      cells by serotype 1 reovirus which is known to infect L cells by the endocytic
      pathway. Time course studies demonstrated that the drugs were effective in
      promoting rotavirus infection of L cells in only the early phases of infection.
      Pretreatment of L cells with dansylcadaverine significantly decreased the number
      of intact, double-shelled rotavirus particles sequestered within the cells.
      Inhibition of endocytosis may increase the efficiency of infection of L cells by
      rotavirus by allowing an increased proportion of attached rotavirus virions to
      enter cells by a productive route which is probably direct membrane penetration.

PMID- 7571413
TI  - Induction of gene expression by intracellular interferon-gamma: abrogation of the
      species specificity barrier.
AB  - We reported previously that murine L-929 cells expressing a human interferon
      (IFN)-gamma cDNA lacking a signal peptide sequence synthesize but fail to secrete
      human IFN-gamma and support viral replication at a reduced level. These cells
      also had elevated levels of IFN-inducible gene products. We show here that a
      similar response is seen in human cells expressing a mutated murine IFN-gamma
      cDNA. The ability of human IFN-gamma to induce gene expression in murine cells is
      shown to be due to the intracellular IFN-gamma rather than to clonal variation,
      induction of endogenous murine IFN, or alternative mediators of antiviral
      activity. We have used a murine cell line, Ltk-aprt-, which is resistant to both
      type I and II IFNs but responsive to combined treatment with both. Ltk-aprt-
      cells transfected with human IFN-gamma cDNA lacking a signal sequence support
      virus replication at the same level as control cells. However, unlike
      transfectants containing only the neoR selection gene, clones expressing the
      mutated human IFN-gamma gene show strong protection against viral infection and
      elevated levels of 2,5 A synthetase mRNA and MHC class I protein after treatment
      with IFN-beta alone. Reverse transcriptase-PCR rules out the induction of
      endogenous murine IFN expression as a mediator of these effects. Thus, expression
      of intracellular human IFN-gamma mimics treatment with extracellular murine IFN
      gamma in permitting a synergistic response to IFN-beta. Given the inability of
      human IFN-gamma to bind to the murine cell-surface receptor our results show that
      intracellular IFN-gamma can activate certain responses independent of cell
      surface binding.

PMID- 7571407
TI  - Characterization of fungally and mechanically transmitted isolates of barley mild
      mosaic virus: two strains in competition.
AB  - The virus populations of two French barley mild mosaic virus isolates have been
      characterized using Western blot, sequence, PCR, and RFLP analyses. One of the
      isolates (M) was obtained by mechanical transmission of the other, fungally
      transmitted isolate (P). The results obtained show that the two isolates contain
      distinct RNA1 and RNA2 molecules with respect to their nucleotide sequences, and
      hence contain distinct barley mild mosaic virus strains. One strain is present
      mainly in isolate P and closely resembles a Japanese and two German isolates. It
      contains an RNA2 of approximately 3.5 kb. The other strain is present mainly in
      isolate M and closely resembles a UK isolate. This strain contains a smaller RNA2
      of approximately 2.4 kb. The results show that mechanical transmission causes a
      shift in the virus populations in favor of the mutant strain.

PMID- 7571414
TI  - The growth advantage conferred by HIV-1 nef is determined at the level of viral
      DNA formation and is independent of CD4 downregulation.
AB  - Recent data on the phenotype of nef-defective HIV-1 in vitro indicate a new
      function of the Nef gene product: enhancement of viral infectivity. Single-cycle
      replication studies have suggested that Nef enhances the efficiency of an early
      step during viral replication, a step that leads to the establishment of viral
      DNA. To test this interpretation, the accumulation of low-molecular-weight
      (unintegrated) viral DNA was measured in cells following exposure to wild-type
      and nef-defective viruses. nef-defective virus accumulated less DNA than the wild
      type. This difference was observed after as little as 5 hr of exposure to virus.
      However, the reverse transcriptase activities of wild-type and nef-defective
      viruses were equal when measured in cell-free assays using either exogenous or
      endogenous templates. In addition, the abilities of these viruses to bind and
      enter cells were not significantly different. Together, these data suggest that
      Nef optimizes postentry events that are required for efficient synthesis of viral
      DNA. To determine if these effects were related to the property of Nef-mediated
      downregulation of CD4, growth curves of these viruses were determined using cells
      that express a CD4 molecule unable to respond to Nef. nef-defective virus
      remained attenuated in these cells, indicating that Nef-mediated downregulation
      of CD4 is not required for Nef-mediated enhancement of viral propagation in
      vitro.

PMID- 7571415
TI  - Serial passage of microglial SIV results in selection of homogeneous env
      quasispecies in the brain.
AB  - The pathogenic effects of HIV include infection of the central nervous system
      (CNS) which can result in cognitive and motor dysfunction. Simian
      immunodeficiency virus (SIV) infection of rhesus macaques provides an excellent
      model of HIV-induced disease. We have achieved a reproducible infection of the
      CNS using a stock of virus obtained by serial passage of microglia-associated
      SIV. Since the envelope genes of both HIV and SIV encode determinants important
      in viral pathogenesis, and the variability inherent in these viruses provides a
      molecular footprint of viral quasispecies, we analyzed the viral env sequences
      resulting from this serial passage. SIV env sequences were analyzed by direct PCR
      amplification of DNA isolated from microglia from infected animals. Nucleotide
      sequence comparison reveals that serial passage of microglia-associated SIV
      resulted in divergence from the donor stock of virus. Furthermore, an enrichment
      of unique env quasispecies which is maintained through the serial passage was
      found in the diseased brains.

PMID- 7571416
TI  - Mutations affecting the UL21 gene contribute to avirulence of pseudorabies virus
      vaccine strain Bartha.
AB  - Analysis of the live attenuated pseudorabies virus (PrV) vaccine strain Bartha
      indicated location of a major determinant for PrV neurovirulence within the
      genomic BamHI fragment 4 (B. Lomniczi et al., 1984, J. Virol. 52, 198-205). To
      more precisely localize the defect, marker rescue experiments were performed
      using cloned subfragments of BamHI-4. Rescuants were analyzed after intracerebral
      infection for their virulence in chicken, as well as after intranasal infection
      for virulence in pigs. We show that the defect associated with attenuation in
      strain Bartha is located in a 3.8-kb subfragment of BamHI-4 which encompasses the
      PrV UL20 and UL21 genes and a putative origin of replication (B. Klupp, H. Kern,
      and T. C. Mettenleiter, 1992, Virology 191, 900-908). Sequence analysis of this
      region of the strain Bartha genome and comparison with the corresponding region
      in wild-type PrV strain Ka revealed the presence of eight point mutations. Four
      nucleotide exchanges reside within the UL21 gene with three of them leading to
      amino acid substitutions; one is located in the intergenic region between the
      UL20 and UL21 genes and three are localized downstream from the UL21 gene.
      Neither the UL20 gene nor the putative origin sequence was affected. Insertional
      inactivation of the UL21 gene in wild-type PrV strain Ka led to a marked
      attenuation of the virus for pigs infected by the intranasal route. In summary,
      our data show that the PrV UL21 gene is a major determinant of PrV virulence and
      that point mutations affecting the UL21 gene of live vaccine strain Bartha
      contribute to its attenuated phenotype.

PMID- 7571417
TI  - Characterization of a repetitive DNA element in a brown algal virus.
AB  - We describe a family of repetitive sequences found in viruses infecting the brown
      alga Feldmannia sp. Previously we have demonstrated that the dsDNA genomes of
      viruses infecting one Feldmannia sp. isolate exist as two size classes of 160 and
      179 kb. Repetitive sequences within these genomes were first demonstrated based
      on the anomalous hybridization among five BamHI fragments from digested virus
      DNA. Sequence analysis of one of those fragments, B2.4, revealed the presence of
      173-bp direct repeats. The restriction maps of the cross-hybridizing BamHI
      fragments in the two FsV (Feldmannia sp. virus) genome size classes show that
      these repeats are not widely dispersed, rather they are confined to a small
      region of each virus genome. We estimate the number of these repeats in the 179
      kb genome to be about 109 and in the 169-kb genome to be about 41. In the 179-kb
      genome, the repeats are contained within a 22-kb region, about 12% of that virus
      genome, and in the 160-kb genome the repeats are contained within a 10-kb region,
      about 6% of the genome. The difference in repeat numbers can account for 62% of
      the size difference between the two size classes of the FsV genome.

PMID- 7571418
TI  - Analysis of herpes simplex virus-specific T cells in the murine female genital
      tract following genital infection with herpes simplex virus type 2.
AB  - A murine model of genital infection with a thymidine kinase-deficient (tk-)
      strain of herpes simplex virus type 2 (HSV-2) was utilized to examine the
      development of the local T cell response in the genital mucosa and draining
      genital lymph nodes (gLN). HSV-specific cytokine-secreting T cells were detected
      in the gLN 4 days postintravaginal inoculation but not in the urogenital tract or
      spleen until 5 days postinoculation, suggesting the cellular immune response
      originates in the gLN. More CD4+ than CD8+ gLN T cells were detected by flow
      cytometric analysis following primary vaginal inoculation and the majority of HSV
      specific gLN T cells detected by ELISPOT were CD4+ and Th1-like based on
      secretion of IFN gamma and not IL-4 or IL-5. A similar population of HSV-specific
      memory T cells persisted in the genital tract 2 months following HSV-2 tk-
      genital inoculation. These data suggest that the urogenital cellular immune
      response elicited in mice following genital inoculation with HSV-2 tk- is
      predominantly CD4+ and Th1-like, resembling that observed in humans. The results
      of this study are important for the rational design of vaccines capable of
      inducing protective immunity in the genital tract.

PMID- 7571420
TI  - Biochemical analysis of the N-glycosylation pathway in baculovirus-infected
      lepidopteran insect cells.
AB  - The baculovirus-insect cell system is used routinely for foreign glycoprotein
      production, but the precise nature of the N-glycosylation pathway in this system
      remains unclear. Some studies indicate that these cells cannot process N-linked
      oligosaccharides to complex forms containing outer-chain galactose and sialic
      acid, while others indicate that they can. In this study, we used the major
      virion envelope glycoprotein of the baculovirus Autographa california multicapsid
      nuclear polyhedrosis virus (AcMNPV) to probe the N-glycosylation pathway in
      baculovirus-infected lepidopteran insect cells. The results showed that gp64
      contained mannose, fucose, and probably N-acetylglucosamine, but no detectable
      galactose or sialic acid. These same results were observed with gp64 produced in
      any one of three different lepidopteran insect cell lines derived from Spodoptera
      frugiperda, Trichoplusia ni, or Estigmene acrea, whether it was produced at
      relatively earlier or later times after infection. These results indicated that
      the gp64 produced in AcMNPV-infected lepidopteran insect cells lacks complex N
      linked oligosaccharides containing outer-chain galactose and sialic acid. By
      contrast, gp64 produced in mammalian cells contained both galactose and sialic
      acid, and endoglycosidase digestions revealed that these sugars were constituents
      of N-linked, not O-linked, oligosaccharides. This showed that at least one N
      linked side chain on gp64 has the potential to be processed to a complex form.
      Together, these results suggest either that AcMNPV-infected lepidopteran insect
      cells are unable to convert any of the N-linked side chains on gp64 to complex
      structures or that outer-chain galactose and sialic acid residues are added to
      gp64 and then removed by cellular or viral exoglycosidases.

PMID- 7571421
TI  - The envelope proteins of lactate dehydrogenase-elevating virus and their membrane
      topography.
AB  - We have studied the membrane topography and N-glycosylation of the envelope
      proteins of lactate dehydrogenase-elevating virus (LDV, strain P). Transcripts of
      open reading frames (ORFs) 2, 5, and 6 were in vitro translated in the absence
      and presence of microsomal membranes, and the products analyzed for molecular
      weight, sensitivity to endoglycosidase F/N-glycosidase F and proteinases, and
      reaction with anti-LDV antibodies. The ORF 6 mRNA translation was enhanced in the
      presence of microsomal membranes. ORF 6 encodes a polytopic class III membrane
      protein identified as the nonglycosylated virion envelope protein (M/VP-2;
      approximately 18 kDa). The protein has a very short (about 11 amino acids)
      ectodomain, a longer (about 79 amino acids) C-terminal endodomain, and crosses
      the membrane three times between these domains. ORF 5 encodes the primary virion
      envelope glycoprotein (VP-3P) (25-42 kDa). Our results suggest that it is a
      polytopic class I glycoprotein. After removal of a signal peptide, the processed
      protein of about 171 amino acids consists of a short (approximately 30 amino
      acids) N-terminal ectodomain with three asparagine residues that appear to be N
      glycosylated, a segment that crosses the membrane three times, and an about 74
      amino acid long C-terminal endodomain. Neutralizing anti-LDV antibodies are
      probably directed to an epitope(s) in the N-terminal ectodomain. The ORF 2
      protein is a standard class I glycoprotein with a single C-terminal membrane
      anchor segment and its signal peptide is removed during membrane-associated
      synthesis. The remaining ectodomain (about 165 amino acids) contains three
      asparagine residues which appear to be N-glycosylated. Our results suggest that
      the ORF 2 protein may be present in a low concentration in LDV virions (VP-3M).

PMID- 7571419
TI  - Clonal variations among multiple primary mammary tumors and within a tumor of
      individual mice: insertion mutations of int oncogenes.
AB  - Laboratory mice infected with the mouse mammary tumor virus (MMTV) often develop
      multiple mammary tumors. However, no comprehensive studies have been done
      addressing the question of whether or not different primary tumors of individual
      mice are related ontogenetically to each other. Further, it is not known to what
      extent individual tumors vary in their cellular composition. We, therefore,
      examined intertumor and intratumor patterns of the rearrangements in int-1 (Wnt
      1), int-2 (Fgf-3), and int-3 protooncogenes, since mutations in ints caused by
      MMTV result in the development of mammary tumors in mice and thus provide the
      most suitable genetic markers for the tumor cells. Our results show that,
      irrespective of the genetic background of the mice and/or the strain of MMTV, the
      pattern of MMTV integration in the different tumors of individual mice varies as
      widely as is found with the tumors of different mice. Of the 79 tumors obtained
      from 25 mice of different genetic backgrounds, 31 showed insertional mutations in
      int-1 (39%). By contrast only 9 of the 65 tumors tested had mutations in int-2
      (14%). None of the tumors showed mutations in int-3. Interestingly, tumors from
      individual mice also showed variations in their pattern of int gene mutation,
      indicating that multiple tumors that develop in a mouse bear no ontogenetical
      link. The analysis of the pattern of intratumor MMTV integration, int mutation,
      and int expression revealed that several int mutational events as well as
      variations in int expression may occur in the same tumor. The diversity of int
      activation within individual tumors may suggest that the initiation and
      progression of most mammary tumors, if not all, occur through the concerted
      action of different mutational events in the same cell or through interactions of
      different cell populations, each of which acquired different int mutations.

PMID- 7571422
TI  - A fairly conserved epitope on the hemagglutinin of influenza A (H3N2) virus with
      variable accessibility to neutralizing antibody.
AB  - A monoclonal antibody LMBH5 was derived from mice which had been immunized with
      A/Victoria/3/75 (H3N2)-type recombinant, secreted hemagglutinin (HA), and were
      subsequently challenged with a potentially lethal dose of X31 [A/Aichi/2/68
      (H3N2) x A/PR/8/34 (H1N1)] virus. LMBH5 reacted strongly with the native and low
      pH-induced conformations of the HA of A/Aichi (X31 strain) and A/Victoria (X47
      strain), but very weakly with the native structure of the HA of
      A/Philippines/2/82 (X79 strain) and not at all with the HA of A/Guizhou/54/89 H3
      (NIB25 strain). However, the acid-induced conformations of the latter two viruses
      were recognized by LMBH5. The antibody prevented infection of MDCK cells with X31
      and X47, whereas X79 virus was partially neutralized by LMBH5. X31 monoclonal
      escape variants had single amino acid substitutions (Ser 227-->Pro) near the
      interface. The data obtained suggest that the neutralizing LMBH5 reacts with a
      fairly conserved epitope of influenza A (H3N2) virus, which as a result of
      antigenic drift becomes inaccessible in the native state of the HA.

PMID- 7571423
TI  - Mutational analysis of human papillomavirus type 16 E6 protein: transforming
      function for human cells and degradation of p53 in vitro.
AB  - The E6 oncoprotein of human papillomavirus type 16 (HPV 16) [151amino acids (AA)
      long] contains four metal-binding motifs, C-X-X-C, and is postulated to form two
      29-AA finger-like structures in the N-terminal and C-terminal halves, which
      mediate degradation of p53 and binding to p53, respectively. We constructed a
      series of E6 mutants with single-AA substitutions in these finger regions (AAs 34
      62 and 107-135) and examined their transforming function for human embryonic
      kidney (HEK) cells in conjunction with HPV 16 E7 and their interaction with human
      p53 in vitro. The mutants with substitution of L for F-37, G for L-50, S for Y
      54, and P for L-110, which did not transform HEK cells, showed markedly lowered
      activity to direct degradation of p53. The mutants with substitutions of G for R
      39, G for V-42, G for Y-43, L for F-47, and G for V-53 lost the transforming
      function, but they could mediate degradation of p53 at levels comparable to the
      activities of the wild-type and transforming mutants. Like the wild type, all of
      the E6 mutants were localized by immunofluorescence to the nuclei of human TS21B
      cells or monkey COS-1 cells, except for the E6 mutant with substitution of G for
      Y-43 whose expression was undetectable. The levels of E6 mutants metabolically
      labeled in COS-1 cells were comparable to those of the transforming E6s. The data
      indicate that E6-directed degradation of p53 is necessary but not sufficient for
      HPV 16-mediated transformation of of HEK cells.

PMID- 7571424
TI  - Distinct modulation of p53 activity in transcription and cell-cycle regulation by
      the large (54 kDa) and small (21 kDa) adenovirus E1B proteins.
AB  - P53 can both stimulate transcription via the p53-consensus sequence as well as
      inhibit gene expression via CAAT-TATA-sequences. Certain viral and cellular
      proteins can abrogate the p53-dependent stimulation of transcription by physical
      association. In addition, it has been shown that the large E1B protein of
      adenovirus type 12 (Ad12), E1B/54 kDa, can block the transcription activation
      potential of p53, without binding to p53. Here we show that this E1B/54-kDa
      protein also can prevent the repression of transcription of transfected and
      endogenous p53 in transient transfections. In cells containing wild-type p53 but
      stably expressing high levels of E1B/54 kDa, no induction of WAF1 mRNA after X
      ray irradiation could be detected. In contrast, expression of another non-p53
      binding E1B protein, Ad5 E1B/21 kDa has no effect on WAF-1 expression. Results of
      an electromobility shift assay indicated that the abrogation of p53-mediated
      transcription activation by E1B/54 kDa cannot be explained by inhibition of the
      DNA-binding capacity of p53. A biological consequence of expression of E1B/54 kDa
      is the loss of G1 cell-cycle arrest after X-ray irradiation, while cells
      expressing the E1B/21 kDa still arrest in G1 after DNA damage.

PMID- 7571426
TI  - Analysis of the complete nucleotide sequences of goose and muscovy duck
      parvoviruses indicates common ancestral origin with adeno-associated virus 2.
AB  - The complete nucleotide sequences of two parvoviruses isolated from goose and
      muscovy duck were determined. The two virus genomes share 81.9% nucleotide
      sequence identity, indicating that they are closely related. The coding regions
      are bracketed by inverted terminal repeats containing palindromes. This is
      similar to the genome organization of human parvoviruses, adeno-associated virus
      2, and B19. Amino acid sequence comparison shows that the closest relative of the
      goose and muscovy duck parvoviruses is adeno-associated virus 2. This is
      surprising, because the goose and muscovy duck parvoviruses do not require any
      helper virus for productive replication, suggesting that adeno-associated virus 2
      has been derived from a helper-independent ancestor.

PMID- 7571425
TI  - European swine virus as a possible source for the next influenza pandemic?
AB  - According to phylogenetic data, about 100 years ago an avian influenza virus
      passed the species barrier (possibly first) to pigs and (possibly from there) to
      humans. In 1979 an avian influenza A virus (as a whole, without reassortment)
      again entered the pig population in northern Europe, forming a stable lineage.
      Here it is shown that the early North European swine viruses exhibit higher than
      normal evolutionary rates and are highly variable with respect to plaque
      morphology and neutralizability by monoclonal antibodies. Our results are
      consistent with the idea that, in order to pass the species barrier, an influenza
      A virus needs a mutator mutation to provide an additional number of variants,
      from which the new host might select the best fitting ones. A mutator mutation
      could be of advantage under such stress conditions and might enable a virus to
      pass the species barrier as a whole even twice, as it seems to have happened
      about 100 years ago. This stressful situation should be over for the recent swine
      lineage, since the viruses seem to be adapted already to the new host in that the
      most recent isolates--at least in northern Germany--are genetically stable and
      seem to have lost the putative mutator mutation again.

PMID- 7571427
TI  - De novo generation of defective interfering-like RNAs in broad bean mottle
      bromovirus.
AB  - Broad been mottle virus (BBMV) is the only member of the bromoviruses that is
      known to accumulate defective-interfering (DI) RNAs (Romero et al., Virology 194,
      576-584, 1993). De novo generation of DI-like RNAs was demonstrated during serial
      passages of BBMV in broad bean using either DI RNA-free virion RNA preparations
      or transcribed genomic RNA inocula. As for previously described DI RNAs, all but
      one of the characterized de novo generated DI-like RNAs were derived by a single
      in-frame deletion from the RNA2 component. The sole exception was derived by two
      shorter in-frame deletions from RNA2. The maintenance of an open reading frame by
      all DI-like RNAs suggests the importance of coding capacity and/or the shortened
      2a protein in the accumulation of these RNAs during infection. The deletion
      junction sites were between nucleotides 1152 and 2366, suggesting that the
      retained regions are essential for the efficient accumulation of BBMV DI-like
      RNAs in planta. Short regions of sequence similarity and/or complementarity were
      revealed at the 5' and 3' junction borders. We speculate that these regions can
      facilitate DI (DI-like) RNA formation. In addition to DI-like RNAs, the full
      length nucleotide sequences of RNA2 components of the Type and Morocco strains of
      BBMV are presented.

PMID- 7571428
TI  - Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of
      Japanese encephalitis virus induce significant protection in mice against lethal
      JEV infection.
AB  - A series of double-subgenomic Sindbis virus (dsSIN) recombinants that express
      cassettes encoding the immunogenic proteins of Japanese encephalitis virus (JEV)
      [prM-E, prM-E-NS1, NS1-NS2A, 80%E (encodes the amino-terminal 80% part of E), and
      NS1] were constructed and analyzed for their ability to confer protective
      immunity in mice against lethal challenge with neurovirulent JEV. The cassettes
      were introduced into both 5' [second subgenomic promoter of the vector precedes
      the SIN structural open reading frame (SP-ORF)] and 3' (the promoter follows the
      SP-ORF) dsSIN vectors. The longest cassette (prM-E-NS1) was 3.2 kb in length,
      which is remarkable for such a small vector virus as SIN (SIN genome is roughly
      11.8 kb in length). The level of expression of JEV proteins appeared similar for
      both 5' and 3' recombinants. In general, the stability of the recombinants
      obtained was found to be low (expression was lost following one to five passages
      at low multiplicity of infection, depending on the recombinant). However, 5'
      recombinants containing longer cassettes (prM-E-NS1, prM-E, NS1-NS2A) were more
      stable than the corresponding 3' recombinants. Intraperitoneal inoculation of
      mice with 10(7) PFU of dsSIN-JEV recombinants induced antibodies against JEV
      proteins and low titers of JEV-neutralizing antibodies were produced by mice
      inoculated with recombinants expressing 80%E, prM-E, and prM-E-NS1. A single
      immunization of mice with the dsSIN-prM-E or dsSIN-prM-E-NS1 recombinants
      provided 40-65% protection against peripheral lethal challenge with 10(4) LD50 of
      neurovirulent JEV. The results demonstrate that genetically engineered
      togaviruses can be successfully used as vaccine vectors.

PMID- 7571429
TI  - Virion positions and relationships of lactococcal temperate bacteriophage TP901-1
      proteins.
AB  - The major proteins of phage TP901-1 virion were characterized by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and structural relations were
      determined using specific antibodies, obtained by affinity purification from a
      polyclonal serum. A 23-kDa protein was identified as the major tail protein, and
      a 31-kDa molecule as the major head protein, respectively. Labeling experiments
      with antibodies against two proteins, with molecular masses of 20 and 19 kDa,
      indicated that they were baseplate-related components. A 72-kDa protein was found
      to be part of a neck passage structure, which includes a collar. Evidence for the
      presence of attached whiskers was also obtained. T7 RNA polymerase-mediated
      expression of the two major proteins confirmed the gene location of the
      previously sequenced region of the phage genome. The relation to other
      lactococcal phages was determined by DNA hybridization and antibody probing,
      showing that despite low DNA similarity, TP901-1 NPS epitopes were detected in
      both related and unrelated small isometric-headed phages.

PMID- 7571430
TI  - Virion formation is required for the long-distance movement of red clover
      necrotic mosaic virus in movement protein transgenic plants.
AB  - The red clover necrotic mosaic dianthovirus (RCNMV) genome is split between two
      single-stranded RNA species. The polycistronic RNA-1 encodes the viral RNA
      polymerase and capsid protein (CP) and the monocistronic RNA-2 encodes the 35 kDa
      cell-to-cell movement protein (MP). Nicotiana benthamiana plants transformed with
      the RCNMV MP gene were generated. When inoculated onto the MP transgenic plants,
      cell-to-cell movement of RNA-1 occurred at a rate similar to wild-type virus.
      However, long-distance (leaf-to-leaf) movement of RNA-1 was not observed. Neither
      CP nor virions were detected in the inoculated leaves of the MP transgenic
      plants. When RNA-1 was coinoculated with RNA-2 mutants, which do not express a
      functional MP, onto MP transgenic plants, CP and virions were readily detected
      and a systemic infection resulted. These results demonstrate that both RNA-1 and
      RNA-2 are necessary for the accumulation of both CP and virions. Furthermore, CP
      accumulation was found to be required for long-distance movement of RCNMV.
      Therefore, these data provide evidence that CP, in the form of virions, is
      necessary for the long-distance movement of RCNMV.

PMID- 7571431
TI  - A 10-amino-acid linear sequence of VP1 of foot and mouth disease virus containing
      B- and T-cell epitopes induces protection in mice.
AB  - The area of foot and mouth disease virus (FMDV) comprising residues 140 and 160
      of capsid protein VP1 has been used extensively as an immunogen in natural and
      experimental hosts. A detailed epitope mapping of this region, however, has not
      been reported. For this purpose a synthetic peptide containing the residues 135
      to 160 (p135-160) of VP1 of FMDV O1 Campos was analyzed for its T- and B-cell
      epitopes. The p135-160 is highly immunogenic, either by itself or coupled to a
      carrier protein (BSA), elicits a long-lasting neutralizing antibody response in
      mice, and provides solid protection against virulent challenge. By using a set of
      synthetic 10mer overlapping peptides, which cover the entire sequence 135-160 of
      VP1, we have shown that at least four discrete B epitopes are regularly
      distributed along the peptide. Although immunization with each of the 10mers
      coupled with BSA as a carrier protein induced peptide-specific antibody
      responses, individually none of the 10mers was able to induce neutralizing
      antibodies. However, anti-135-160 antibodies sorted by immunoaffinity
      chromatography using each of the 10mers revealed the existence of at least four
      discrete neutralizing sites: one spanning residues 135-144, at least two more
      between residues 140 and 154, and another in the region 150-160. Moreover, T-cell
      epitopes were identified, both by antigen-dependent proliferation assays and by
      adoptive cell transfer. By both methods, a T-cell epitope was located in the area
      comprising residues 135-144; the cell transfer experiment, which seems to be more
      sensitive, also identified a second T-cell epitope between residues 150 and 160.
      Interestingly, when the region 135-144, which contains both B- and T-cell
      epitopes, was in a tandem repeat configuration it induced a strong neutralizing
      antibody response in mice and solid protection against the challenge.

PMID- 7571432
TI  - The molecular genetics of feline coronaviruses: comparative sequence analysis of
      the ORF7a/7b transcription unit of different biotypes.
AB  - Feline coronaviruses (FCoVs) have been subdivided into feline enteric
      coronaviruses (FECVs) and feline infectious peritonitis viruses (FIPVs) on the
      basis of pathogenic properties. Serologically, a distinction has been made
      between type I and II FCoVs, the latter of which more closely resemble canine
      coronavirus (CCV). To gain more insight into the genetic relationships between
      different FCoV biotypes, we determined the nucleotide sequences of the ORF7a/7b
      transcription unit of nine strains. The following observations were made: (i) The
      sequences are 87-100% identical. In this part of the genome, type I and II FCoVs
      are more closely related to each other than to CCV. To explain the genetic and
      antigenic differences between the spike genes of type I and II FCoVs, we
      postulate that type II FcoVs have arisen by an RNA recombination event between a
      type I FCoV and CCV. (ii) The avirulent "FECV" strains UCD and 79-1683 are more
      similar to virulent "FIPV" strains than to each other. Our findings thus support
      the notion that FECV and FIPV are not different species but merely virulence
      variants. (iii) In contrast to FECV 79-1683, FECV UCD contains an intact ORF7b,
      indicating that ORF7b deletions are not a universal distinguishing property of
      FECVs. (iv) ORF7b deletions readily occur in vitro, correlating with loss of
      virulence. By reverse transcription-polymerase chain reaction analysis, we show
      that in naturally occurring FCoVs ORF7b is maintained. Thus, ORF7b seems to
      provide a distinct selective advantage during natural infection.

PMID- 7571433
TI  - Characterization of a temperate Streptococcus thermophilus bacteriophage and its
      genetic relationship with lytic phages.
AB  - The temperate Streptococcus thermophilus bacteriophage phi SFi21 showed an 38-kb
      long double-stranded DNA genome with cohesive ends. A single integration site was
      used in lysogens established in three different S. thermophilus strains. The attP
      and attB sites were localized on the restriction map of phage DNA and by
      hybridization on pulsed field separated bacterial DNA. All laboratory-established
      lysogens showed in addition to integrated prophage DNA unintegrated monomer phage
      DNA with unligated cos sites. The genetic relatedness of phi SFi21 DNA with DNA
      from lytic phages was studied in dot blot and Southern blot hybridization by
      using individual restriction fragments of phiSFi21 DNA as probes. Lytic group I
      phages hybridized with fragments of the central and the right part of the
      phiSFi21 genome but failed to hybridize with a fragment joining both parts. Lytic
      group II phages showed hybridization with the right half of the phiSFi21 genome.
      In lytic group IV phages, biologically a heterogeneous group, many different
      combinations of cross hybridization were detected in accordance with the
      hypothesis of the modular evolution of phage genomes.

PMID- 7571434
TI  - Recombinant duck interferon: a new reagent for studying the mode of interferon
      action against hepatitis B virus.
AB  - Although interferon is widely used to treat chronic hepatitis B virus infections,
      its mode of action against hepadnaviruses is largely unknown. This deficit is due
      mainly to the lack of suitable model systems. The duck system could not be used
      because purified duck interferon was not available in sufficient quantities. We
      have now cloned a DNA fragment that contains an intronless gene for duck
      interferon. The primary translation product consists of 191 amino acids, the N
      terminal 30 residues of which constitute a signal peptide. Mature duck interferon
      is 50% identical to the recently cloned chicken interferon. Sequence homology to
      mammalian interferons is marginal, but conservation of four cysteine residues and
      inducibility by virus indicate a distant relationship between duck interferon and
      mammalian type I interferons. Purified recombinant duck interferon from
      Escherichia coli is biologically active: it activates the interferon-inducible Mx
      gene, prevents cell destruction by cytolytic RNA viruses, and has a strong
      inhibitory effect on duck hepatitis B virus in cultured primary duck hepatocytes.
      This new reagent should help to define the interferon-sensitive step of the
      hepadnavirus life cycle. Furthermore, the duck system can now be used for
      systematic studies of the in vivo effectiveness of interferon in chronic
      hepatitis B virus infections.

PMID- 7571435
TI  - Replication of Orgyia pseudotsugata baculovirus DNA: lef-2 and ie-1 are essential
      and ie-2, p34, and Op-iap are stimulatory genes.
AB  - A transient DNA replication assay was used to identify genes located within m.u.
      90.5-7.0 of the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus
      (OpMNPV) genome that influenced replication of a reporter plasmid containing an
      OpMNPV origin of replication, when cotransfected into uninfected Lymantria dispar
      cells. The viral transactivator ie-1 and a 2.4-kb subclone were found to be
      essential for replication. The 2.4-kb region was sequenced and open reading
      frames were identified. Replication assays using subclones from this region
      identified a gene called late expression factor 2 (lef-2), as the essential
      replication gene. The OpMNPV lef-2 gene encodes a protein with a predicted
      molecular weight of 22.7 kDa (204 amino acids) and exhibits 54.7% amino acid
      sequence identity with its homolog in the genome of the Autographa californica
      MNPV. Transcriptional mapping using both Northern blot and S1 nuclease protection
      assays demonstrated that OpMNPV lef-2 was expressed at both early and late times
      postinfection as a transcript of about 1.6 kb. The early transcript initiated
      approximately 30 nt downstream of a TAATA box, whereas the late transcript
      initiated from within a late promoter consensus motif. In addition, we identified
      three genes stimulatory for DNA replication including two OpMNPV transcriptional
      activators (ie-2 and p34) and Op-iap, which is the functional analog of the
      AcMNPV p35 gene that inhibits apoptosis in AcMNPV-infected Spodoptera frugiperda
      cells.

PMID- 7571436
TI  - Characterization of sequences controlling the synthesis of alfalfa mosaic virus
      subgenomic RNA in vivo.
AB  - RNA 3 of alfalfa mosaic virus encodes the movement protein P3 and the viral coat
      protein (CP). CP is translated from a subgenomic (sg) messenger, RNA 4. To
      characterize the sg promoter that is responsible for RNA 4 synthesis in vivo,
      putative sg promoter sequences were inserted in a unique Xhol site located
      between the initiation codon of the P3 gene and a second in-frame ATG codon in an
      infectious cDNA clone of RNA 3. Mutants with an active sg promoter insert
      expressed an N-terminally truncated P3 protein and were able to accumulate in
      plants. In addition, sg promoter activity was analyzed in protoplasts. When the
      transcription start site is taken as +1, the sequence of nucleotides -26/+1 was
      found to have a basal level of sg promoter activity. This activity was increased
      to near maximum levels when the sg promoter sequence was extended to -136/+12.
      The upstream positive regulatory element was mapped to nucleotides -136/-94.
      Engineering of point mutations and small deletions in RNA 3 around the
      transcription start site for RNA 4 synthesis revealed elements important for sg
      promoter activity with similarity to sequences conserved in sg promoters of alpha
      like viruses. Some of these elements appeared to be required in cis for RNA 3
      accumulation. A deletion of the C-terminal three amino acids of the P3 protein
      rendered this protein nonfunctional in cell-to-cell movement.

PMID- 7571437
TI  - Identification and preliminary characterization of a chitinase gene in the
      Autographa californica nuclear polyhedrosis virus genome.
AB  - A functional chitinase gene (chiA) has been identified in the genome of the
      Autographa californica nuclear polyhedrosis virus (AcMNPV). It is expressed in
      the late phase of virus replication in insect cells. High levels of both endo-
      and exochitinase activity were detected by 12 hr p.i. and remained stable
      throughout infection. An AcMNPV chiA protein-specific antibody was prepared using
      recombinant material prepared in bacteria. This was used to demonstrate that a
      product of approximately 58 kDa was synthesised in virus-infected cells.
      Immunofluorescence analysis of virus-infected cells showed that most chitinase
      was located in the cytoplasm. Primer extension analysis of mRNA from AcMNPV
      infected cells confirmed that transcription initiated from a baculovirus late
      start site (TAAG), 14 nucleotides upstream from the putative translation
      initiation codon. The predicted protein sequence of the AcMNPV chiA shares
      extensive sequence similarity with chitinases from bacteria and, in particular,
      the Serratia marcescens chitinase A (60.5% identical residues). Phylogenetic
      analyses indicate that AcMNPV, or an ancestral baculovirus, acquired the
      chitinase gene from a bacterium via horizontal gene transfer.

PMID- 7571438
TI  - An infectious cDNA clone of a cytopathic hepatitis A virus: genomic regions
      associated with rapid replication and cytopathic effect.
AB  - Rapidly replicating, cytopathic (rr/cpe+) variants of hepatitis A virus (HAV)
      isolated from persistently infected BS-C-1 cells have numerous mutations from
      cell culture-adapted rr/cpe- HAV. To determine which mutations in one rr/cpe+
      virus, HM175/18f, determine enhanced replication in BS-C-1 cells, a series of
      chimeric viruses was rescued from infectious cDNAs in which HM175/18f genomic
      segments were placed within the background of a related rr/cpe- virus, HAV/7.
      Chimeric viruses containing the P2 region of HM175/18f produced replication foci
      in BS-C-1 cells that were larger than HAV/7, but not as large as HM175/18f virus.
      Enhanced viral replication required mutations in both 2B and 2C proteins,
      suggesting that these proteins remain closely associated during replication.
      Mutations in 5' nontranslated RNA (5'NTR) or P3 proteins had no independent
      effect, but acted cooperatively with mutations in P2 proteins to enhance
      replication and render the virus capable of conventional plaque formation.
      Cytopathic effects correlated with viral replication capacity and were not the
      result of any single mutation. Full expression of the rr/cpe+ phenotype required
      mutations within the 5'NTR, P2, and P3 segments. These results suggest novel
      interactions between the 5'NTR and P2 proteins during HAV replication and provide
      useful new infectious cDNA clones.

PMID- 7571439
TI  - The establishment of a genetic map of orf virus reveals a pattern of genomic
      organization that is highly conserved among divergent poxviruses.
AB  - The large differences between the G+C content of the orf virus genome and those
      of other characterized poxviruses have precluded the use of DNA hybridization to
      establish a gene map of orf virus. Here we have sequenced the ends of cloned
      restriction endonuclease fragments of the nZ2 strain of orf virus (OV) and used
      the translated sequences to search protein data bases. Sequence from 15 points
      found high-scoring matches to data base entries, including 18 vaccinia virus
      (VAC) genes. We also present 2 kb of sequence from a region near the right
      terminus of the OV genome and show that it encodes homologs of VAC genes, F9L and
      F10L. The data presented here in conjunction with published and as yet
      unpublished data have allowed the construction of a gene map of OV on which 37
      genes have been placed. Thirty-two of these genes have homologs in VAC. Alignment
      of the OV gene map with that of VAC revealed that each OV gene and its VAC
      counterpart occurred in the same order and orientation on their respective
      genomes. The intervals between many of the points of sequence were also found to
      be strikingly similar. The conserved spacing of genes between OV and VAC within
      the central 88.2 kb of the 139-kb OV genome is not maintained in the termini
      where insertion, deletion, and translocation have occurred. Parallels are drawn
      between the data presented here and related data from swinepox virus and capripox
      virus.

PMID- 7571440
TI  - Intra- and intermolecular nonenzymatic ligations occur within transcripts derived
      from the peach latent mosaic viroid.
AB  - We report here the nonenzymatic self-ligation of transcripts corresponding to the
      peach latent mosaic viroid (PLMVd). This is the first description of this process
      with viroid sequences, although it has been reported to occur with human
      hepatitis delta virus RNA. Self-ligation occurs when the 5'-hydroxyl and the
      2',3'-cyclic phosphate termini produced by the hammerhead self-cleavage of the
      viroid RNA are juxtaposed by the viroid rod-like structure, and a phosphodiester
      bond is formed between the two following hydrolysis of the cyclic phosphate. Unit
      length transcripts undergo intramolecular folding, and their subsequent self
      ligation produces circular molecules. The self-ligation observed in vitro may
      contribute to PLMVd circularization during rolling circle replication; however,
      this does not exclude the possibility that a host RNA ligase catalyzes the
      ligation steps in vivo. Like self-cleavage, self-ligation is probably an
      ancestral reaction, and the enzyme-catalyzed ligation most likely evolved from
      this primitive mechanism. Furthermore, the intermolecular self-ligation of
      annealed transcripts derived from PLMVd is demonstrated, suggesting a possible
      mechanism for sequence reassortment in viroids.

PMID- 7571441
TI  - Natural simian virus 40 strains are present in human choroid plexus and
      ependymoma tumors.
AB  - Simian virus 40 (SV40) sequences for large tumor antigen (T-ag) were recently
      detected in a significant fraction of certain human brain tumors of early
      childhood (Bergsagel et al., N. Engl. J. Med. 326, 988-993, 1992). In the current
      study, we sought to determine whether authentic SV40 was present in the choroid
      plexus and ependymoma tumors previously examined. Polymerase chain reaction and
      DNA sequence analysis revealed authentic SV40 regulatory region and major capsid
      (VP1) sequences in 14 of 17 tumors tested. Only one 72-basepair element was
      detected in the SV40 enhancer region of positive tumor samples, an arrangement
      designated as "archetypal." The C terminus of the T-ag gene was detected in the
      same 14 tumors and was sequenced from 5 tumors; some nucleotide changes were
      found that would result in amino acid changes in T-ag. Infectious SV40 was
      isolated from one sample after lipofection of tumor DNA into monkey kidney cells.
      Sequence analysis of the rescued virus SVCPC revealed (i) an archetypal
      regulatory region, (ii) nucleotide changes in the C terminus of the T-ag gene
      that distinguished it from SV40 laboratory strains 776 and SV40-B2 and from human
      isolate SVPML-1, and (iii) identity with previous human brain tumor isolate SVMEN
      in the three genomic regions sequenced. No human-isolate-specific distinguishing
      features were detected among the viral sequences analyzed. Thus, authentic SV40
      is present in humans and associated with two tumor types known to be induced
      experimentally by the virus.

PMID- 7571443
TI  - High resolution genome typing and genomic reassortment events of rice dwarf
      Phytoreovirus.
AB  - Genomic reassortment of rice dwarf Phytoreovirus (RDV) was experimentally
      demonstrated for the first time in plant reoviruses. Combinations of two genomic
      variants, most of the genomic segments of which could be distinguished by a high
      resolution polyacrylamide gel electrophoresis, were used to produce genomic
      reassortants. After artificial mixed injection of two of three isolates (RDV-S,
      RDV-AI, and RDV-AN) into the insect vector Nephotettix cincticeps, rice seedlings
      were sequentially inoculated and the genomic origin of the viruses present in the
      infected plants was examined by electrophoresis. The progeny virus population
      contained either one or both of the respective genomic segments from the parents.
      Genomic segments reassorted randomly except for genome segment 1 (S1) and S9. S9
      of RDV-S was mostly excluded in the reassortants in both the insects and the
      infected plants when it was mixed with RDV-AI or RDV-AN. On the other hand, S9
      reassorted randomly in most of the virus populations in infected plants when RDV
      AI and RDV-AN were co-injected into insects. When RDV-S and RDV-AI were mixed, S1
      from RDV-S was present more frequently in the infected plants although both
      parental S1's were present in equimolar amounts in insects.

PMID- 7571442
TI  - 5' regions of HIV-1 RNAs are not sufficient for encapsidation: implications for
      the HIV-1 packaging signal.
AB  - The location and nature of the HIV-1 packaging signal are largely unknown,
      despite several genetic and biochemical mutational analyses. In this report we
      present our attempts to define a minimal HIV-1 packaging signal through the
      generation of test RNAs containing small blocks of HIV-1 sequences. We
      constructed RNAs differing in the position and identity of the HIV-1 sequence and
      the segments of heterologous sequences. However, none of the vectors were
      efficiently, encapsidated by wild-type HIV-1 virions. These results contrast
      those of Moloney murine leukemia virus and Rous sarcoma virus, where small viral
      segments mediate the efficient encapsidation of heterologous RNAs. The results
      suggest that the HIV-1 packaging signal may be extremely dispersed or heavily
      context-dependent.

PMID- 7571444
TI  - Identification of hypervariable and conserved regions in the surface envelope
      gene in the bovine lentivirus.
AB  - The surface envelope (SU) gene of nine different isolates of the bovine
      lentivirus (BIV) were compared for nucleotide and deduced amino acid (aa)
      sequence diversity. Analyses were done both on isolates derived from the original
      reference strain, R29, and on field isolates of BIV. Six conserved and six
      hypervariable regions were identified. Many of the hypervariable regions were
      located in areas predicted to be on the surface of the SU protein. The SU gene
      comparison among all isolates showed up to a 50% aa sequence divergence. When a
      conserved region of the reverse transcriptase gene was compared among eight of
      the isolates, there was less than 11% aa sequence divergence. When comparing all
      isolates, the greatest size differences in the SU gene are observed in the 2nd
      hypervariable region (V2) with up to a 104-aa difference between the largest and
      smallest variant. R29-106, an infectious molecular clone of the original isolate
      of BIV, has an 87-bp deletion in V2 as compared to prototype isolate R29-127. All
      R29-derived isolates sequenced for this study had a SU gene size similar to R29
      106. The four field isolates sequenced for this study had SU genes larger than
      R29-127. R29-derived isolates may not be representative of BIV currently present
      in United States cattle.

PMID- 7571446
TI  - Distant strains of the fish rhabdovirus VHSV maintain a sixth functional cistron
      which codes for a nonstructural protein of unknown function.
AB  - We used direct RNA sequencing to determine the genomic organization of the region
      downstream from the G gene of viral hemorrhagic septicemia virus (VHSV), a fish
      rhabdovirus. This region contains a gene coding for a protein, identified as
      nonvirion protein (NV), and the gene coding for the RNA polymerase (L). Thus,
      VHSV genome organization was confirmed to be 3'-N-P-M-G-NV-L-5'. In both a
      virulent European (07-71) and an avirulent North American (Makah) strain, the NV
      gene is transcribed into a small mRNA that codes for a protein of 122 amino
      acids. It has no significant sequence similarity with the infectious
      hematopoietic necrosis virus NV protein nor with any other known protein. We
      expressed the NV protein as a fusion protein with the glutathione S-transferase
      of Schistosoma japonicum and used the purified fusion protein to immunize
      rabbits. The rabbit antiserum precipitated from infected cell extracts--and not
      from noninfected cells or purified virions--a protein of 14 kDa, well in
      accordance with the expected NV gene product size. The prediction that the NV
      protein is a nonstructural protein is supported by its absence from mature
      virions although it is present in infected cells.

PMID- 7571445
TI  - Sequence analysis of the UL39, UL38, and UL37 homologues of bovine herpesvirus 1
      and expression studies of UL40 and UL39, the subunits of ribonucleotide
      reductase.
AB  - We sequenced the region of the bovine herpesvirus type 1 (BHV-1) genome
      corresponding to map units 0.172-0.230 (7964 bp), representing the UL39, UL38,
      and UL37 homologues of herpes simplex virus which encode the large subunit of
      ribonucleotide reductase (RR) and components of the viral capsid and the
      tegument, respectively. To discriminate between two potential initiator AUGs of
      the UL39 gene, the 5' end of the mRNA was mapped by S1 nuclease protection
      assays. Comparison of the amino acid sequences of the three BHV-1 proteins with
      analogous polypeptides from several other herpesviruses revealed significant
      levels of homology. We also compared the expression kinetics of the large (R1,
      UL39) versus the small (R2, UL40) RR subunits during the course of in vitro BHV-1
      infection by Western blotting using specifically developed and calibrated
      antisera. Our results show that the R1 protein was synthesized earlier than its
      R2 counterpart. Moreover, the R1 protein accumulated to a higher level than the
      R2 protein even though the R2 transcript was in greater abundance than the R1
      mRNA. This is discussed with regard to the translational efficiency of their
      transcripts.

PMID- 7571447
TI  - A transmissible gastroenteritis coronavirus nucleoprotein epitope elicits T
      helper cells that collaborate in the in vitro antibody synthesis to the three
      major structural viral proteins.
AB  - Four strong T cell epitopes have been identified studying the blastogenic
      response of lymphocytes from haplotype-defined transmissible gastroenteritis
      virus (TGEV) immune miniswine to sixty-one 15-mer synthetic peptides. Three of
      these epitopes are located on the nucleoprotein (N46, amino acids 46 to 60; N272,
      amino acids 272 to 286; and N321, amino acids 321 to 335), and one on the
      membrane protein (M196, amino acids 196 to 210). N321 peptide induced the highest
      T cell response and was recognized by immune miniswine lymphocytes with
      haplotypes dd, aa, and cc. T lymphocytes from peptide N321-immune miniswine
      reconstituted the in vitro synthesis of TGEV-specific antibodies by complementing
      CD4- TGEV-immune cells. This response was directed at least against the three
      major structural proteins. The synthesized antibodies specific for S protein
      preferentially recognized discontinuous epitopes and neutralized TGEV
      infectivity. These results show that peptide N321 defines a functional T helper
      epitope eliciting T cells capable of collaborating with B cells specific for
      different proteins of TGEV.

PMID- 7571449
TI  - [Human prion diseases and experimental transmission].

PMID- 7571448
TI  - Characterization of a novel syncytium-inducing baboon reovirus.
AB  - A syncytium-inducing reovirus was recently isolated from brain homogenates of a
      baboon suffering from acute, progressive meningoencephalo myelitis. This baboon
      reovirus (BRV) was classified as a member of the genus Orthoreovirus, family
      Reoviridae, on the basis of the characteristic capsid morphology and genome and
      protein profiles. We have assessed the relationship between BRV and the other
      syncytium-inducing reoviruses in order to determine whether the emergence of this
      virus represents a host range or pathogenic alteration in a previously described
      isolate or the appearance of a novel entity. BRV was compared to representative
      members of the prototype mammalian reoviruses, avian reoviruses, and Nelson Bay
      virus on the basis of electropherotype, protein profile, and antigenic similarity
      as measured by immunoprecipitation using homologous and heterologous antisera. In
      spite of similarities between the genome and protein profiles of BRV and the
      other orthoreoviruses, migration-rate polymorphisms indicate that BRV has
      diverged extensively from the previously described syncytium-inducing
      orthoreoviruses. Most importantly, the limited epitope conservation suggests that
      BRV has existed in genetic isolation from other reoviruses for quite some time.
      We conclude that BRV represents a novel syncytium-inducing mammalian reovirus,
      which is of particular interest in view of its association with disease in
      nonhuman primates during natural infections and its unusual syncytial phenotype.

PMID- 7571450
TI  - [Hepatitis E: etiology and clinics of another enterically transmitted hepatitis].

PMID- 7571452
TI  - [Global eradication project for poliomyelitis].

PMID- 7571451
TI  - Molecular genetics and biophysics of prions.

PMID- 7571453
TI  - [Eradication project for poliomyelitis and surveillance of acute paralysis].

PMID- 7571456
TI  - [Role of clinical laboratories in eradication project for poliomyelitis in
      China].

PMID- 7571454
TI  - [Progress on eradication project for poliomyelitis in Mekong-delta area in
      Vietnam].

PMID- 7571455
TI  - [Eradication project for poliomyelitis in Laos].

PMID- 7571457
TI  - [Role of laboratory diagnosis in eradication project for poliomyelitis in
      countries of west Pacific-Ocean area].

PMID- 7571458
TI  - [Pathogenic mechanism of Sendai virus--virus activation and germination polarity
      by host proteases].

PMID- 7571459
TI  - [Dynamics of influenza virus pathogenicity].

PMID- 7571460
TI  - [Analysis of HIV-1 pathogenicity using SCID-hu mice].

PMID- 7571461
TI  - A four-surface schematic eye of macaque monkey obtained by an optical method.
AB  - Schematic eyes for four Macaca fascicularis monkeys were constructed from
      measurements of the positions and curvatures of the anterior and posterior
      surfaces of the cornea and lens. All of these measurements were obtained from
      Scheimpflug photography through the use of a ray-tracing analysis. Some of these
      measurements were also checked (and confirmed) by keratometry and ultrasound.
      Gaussian lens equations were applied to the measured dimensions of each
      individual eye in order to construct schematic eyes. The mean total power
      predicted by the schematic eyes agreed closely with independent measurements
      based on retinoscopy and ultrasound results, 74.2 +/- 1.3 (SEM) vs 74.7 +/- 0.3
      (SEM) diopters. The predicted magnification of 202 microns/deg in one eye was
      confirmed by direct measurement of 205 microns/deg for a foveal laser lesion. The
      mean foveal retinal magnification calculated for our eight schematic eyes was 211
      +/- (SEM) microns/deg, slightly less than the value obtained by application of
      the method of Rolls and Cowey [Experimental Brain Research, 10, 298-310 (1970)]
      to our eight eyes but just 4% more than the value obtained by application of the
      method of Perry and Cowey [Vision Research, 12, 1795-1810 (1985)].

PMID- 7571462
TI  - Changes in retinal time scale under background light: observations on rods and
      ganglion cells in the frog retina.
AB  - The kinetics of rod responses to flashes and steps of light was studied as a
      function of background intensity (IB) at the photoreceptor and ganglion cell
      levels in the frog retina. Responses of the rod photoreceptors were recorded
      intracellularly in the eyecup and as ERG mass potentials across the isolated,
      aspartate-superfused retina. The kinetics of the retinally transmitted signal was
      derived from the latencies of ganglion cell spike discharges recorded
      extracellularly in the eyecup. In all states of adaptation the linear-range rod
      response to dim flashes could be modelled as the impulse response of a chain of
      low-pass filters with the same number of stages: 4 (ERG) or 4-6 (intracellular).
      Dark-adapted time-to-peak (tp, mean +/- SD) at 12 degrees C was 2.4 +/- 0.6 sec
      (ERG) or 1.7 +/- 0.4 sec (intracellular). Under background light, the time scale
      shortened as a power function of background intensity, I-bB with b = 0.19 +/-
      0.03 (ERG) or 0.14 +/- 0.04 (intracellular). The latency-derived time scale of
      the rod-driven signal at the ganglion cell agreed well with that of the
      photoreceptor responses. The apparent underlying impulse response had tp = 2.0 +/
      0.7 sec in darkness and accelerated as I-bB with b = 0.17 +/- 0.03. The
      photoreceptor-to-ganglion-cell transmission delay shortened by 30% between
      darkness and a background delivering ca 10(4) photoisomerizations per rod per
      second. Data from the literature suggest that all vertebrate photoreceptors may
      accelerate according to similar power functions of adapting intensity, with
      exponents in the range 0.1-0.2. It is noteworthy that the time scale of human
      (foveal) vision in experiments on flicker sensitivity and temporal summation
      shortens as a power function of mean luminance with b approximately 0.15.

PMID- 7571464
TI  - Effects of luminance contrast and phase difference on motion assimilation for
      sinusoidal gratings.
AB  - When a sinusoidal (test) grating is displaced horizontally by a phase angle of
      180 deg in a two-frame apparent motion display, the perceived direction of motion
      is ambiguous; the test grating appears to move either to the left or to the right
      (or to both directions). On the other hand, when the test grating is displaced by
      180 deg synchronously with the inducing gratings which, presented above and below
      the test grating, jump unambiguously in one direction (e.g. displaced by 90 deg),
      the test grating always appears to move in the same direction as the inducing
      gratings (motion assimilation). In the present study, the effects of luminance
      contrast and phase difference on motion assimilation were examined. The
      proportion of perceived direction of motion (left or right) was measured as a
      function of phase difference between the test grating in the first and the second
      frame. The magnitude of motion assimilation was evaluated as the change in the
      phase difference for which the proportions of observers' response were equal
      (50%) for both directions. The magnitude of motion assimilation increased with
      increase in the contrast of the inducing gratings or with decrease in the
      contrast of the test grating. Also, the magnitude increased as the phase
      difference of the inducing gratings departed from 180 deg. Based on these
      results, a quantitative formulation between the magnitude of motion assimilation,
      and the contrast and the phase difference of the stimulus gratings was derived.
      Further, a model was proposed which explains the stimulus dependences of motion
      assimilation in terms of response-integration among local motion detectors.

PMID- 7571465
TI  - The effects of spatiotemporal integration on maximum displacement thresholds for
      the detection of coherent motion.
AB  - In a series of nine experiments, observers were required to identify the shapes
      of moving targets, and to discriminate regions of motion from regions of
      uncorrelated noise. Maximum displacement thresholds (Dmax) for performing these
      tasks were obtained under a wide variety of conditions. The stimulus parameters
      manipulated included the number of distinct frames in the motion sequences, the
      stimulus onset asynchrony between each frame, the size of the moving dots, and
      the shape, area and eccentricity of the target regions. For two-frame displays
      presented in alternation, the area of the target region was the only one of these
      variables to have any significant effect on Dmax. For longer length sequences, in
      contrast, Dmax varied dramatically among the different conditions over a range of
      10 min arc to 10 deg. In an effort to isolate the specific processes of
      spatiotemporal integration, we also examined how performance is affected by
      having overlapping transparent motions in opposite directions, or by the presence
      of dynamic noise or limited dot lifetimes within the moving target regions. The
      overall pattern of results suggest that Dmax is primarily determined by the
      ability of the visual system to isolate motion signals from the noise produced by
      spurious false target correlations. As a general rule, Dmax will increase as a
      result of any stimulus manipulation that increases the number of local signal
      correlations detected relative to those arising from noise, and vice versa.

PMID- 7571463
TI  - The role of exocentric reference frames in the perception of visual direction.
AB  - One classic piece of evidence for an efference copy signal of eye position is
      that a small, positive afterimage viewed in darkness is perceived to move with
      the eye. When a small stationary reference point is visible the afterimage
      appears to move relative to the reference point. However, this is true only when
      the afterimage is localized to a small area. We have observed that when an
      extended afterimage of a complex scene is generated by a brief, bright flash it
      does not appear to move, even with large changes in eye position. When subjects
      were instructed to maintain their direction of gaze, we observed small saccades
      (typically < 1 deg) and slow drift movements often totalling more than 10 deg
      over a 30 sec period. When the instructions were to simply inspect the extended
      afterimage, subjects made larger saccades (up to 5 deg) which were not
      accompanied by afterimage movement. The smaller movements observed under the
      first instructions are greater than those observed in the dark or with small
      afterimages. When a visible reference is present with these large afterimages,
      the afterimage appears stationary, while the reference point appears to move. Eye
      position was monitored following the generation of such afterimages. In general,
      the perceived motion of the stationary reference point was in a direction
      opposite to the motion of the eye. Similar drift movements of smaller magnitude
      were observed with localized afterimages, but the motion was attributed to the
      afterimage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571466
TI  - Effects of a static textured background on motion integration.
AB  - We studied how the visual system integrates locally ambiguous velocities into
      global unambiguous coherent motion in the presence or absence of a textured
      background. Line drawings of complex figures were presented through invisible
      (i.e. same luminance and hue as the background) circular apertures such that only
      straight line segments were visible. These figures were either presented against
      a uniform background or embedded in static textures made of similar line segments
      in such a way that figures cannot be detected if they remain static. Under our
      experimental conditions, the figures translated clockwise or counterclockwise
      along a circular path and observers were required to discriminate the global
      direction of motion. Because of the aperture problem, a single moving segment
      cannot disambiguate the global direction of the figures and integration across
      multiple line segments is therefore necessary to perform the task. We found that
      with figures at high contrast, the presence of a texture enhanced direction
      discrimination, while direction discrimination of figures at low contrast was
      impaired by the presence of the texture. These paradoxical effects of a static
      texture were further tested by manipulating the relative contrast between figures
      and texture, the motion onset asynchrony (the delay between stimulus onset and
      motion onset or MOA), the density, the orientation and the distribution of
      texture elements. The effects of the texture, either facilitation or suppression,
      increase with texture contrast. Accuracy improves with MOA and decreases with
      texture density. In general, at high figure contrast, accuracy is better whenever
      referents are present in the image. We suggest that facilitation by the texture
      at high figure contrast is accounted for by reduced salience of segmentation cues
      such as line terminators and increased accuracy of local velocity measurements.
      On the other hand, decreased performance at low figure contrast may reflect
      lateral suppression of the responses to motion signals by the texture.

PMID- 7571467
TI  - A target in real motion appears blurred in the absence of other proximal moving
      targets.
AB  - For exposure durations longer than about 40 msec, a field of dots in sampled
      motion has been reported to appear less smeared than predicted from the visual
      persistence of static displays. This reduction of perceived smear has been
      attributed to a motion "deblurring" mechanism. However, it has been long
      recognized that an isolated target moving continuously in a dark field appears to
      be extensively smeared. To reconcile these apparently contradictory observations,
      we investigated the effect of dot density on the extent of perceived smear for a
      single moving dot and for fields of dots with densities ranging from 0.75 to 7.5
      dots/deg2. Bright targets were presented in continuous motion against a
      photopically illuminated background field. The results reconcile previous
      conflicting observations by showing that the length of perceived smear decreases
      systematically with dot density for exposure durations longer than about 50 msec.
      In three additional experiments, we arranged the spatial configuration of the
      targets to evaluate whether motion deblurring results primarily from a motion
      compensation mechanism (such as integration within the spatiotemporally oriented
      receptive fields of putative motion mechanisms) or from inhibition exerted by
      spatiotemporally adjacent targets. The results show that the activation of motion
      mechanisms is not a sufficient condition for motion deblurring and that the
      reduction of perceived smear requires the presence of spatiotemporally adjacent
      targets. Taken together, these findings suggest that motion deblurring results
      primarily from masking exerted by spatiotemporally proximal targets.

PMID- 7571468
TI  - Stereopsis, spatial frequency and retinal eccentricity.
AB  - Stereoscopic depth discrimination thresholds increase with retinal eccentricity
      and distance from the horopter. However, in contrast to spatial resolution, the
      effects of spatial frequency on stereo-thresholds in the periphery are unknown.
      For spatial vision, it is generally assumed that the retina is comprised of a
      series of overlapping spatial filter mechanisms and that there is a commensurate
      increase in spatial scale as a function of retinal eccentricity. If the same
      holds true for mechanisms sensitive to stereoscopic depth, then stereo-thresholds
      for low spatial frequency stereoscopic stimuli may remain relatively invariant
      across the visual field, while thresholds for relatively high spatial frequency
      stimuli would increase. To further understand the role of the disparity sensitive
      mechanisms involved in depth discrimination, increment depth discrimination
      thresholds for both crossed and uncrossed disparities were measured as a function
      of eccentricity for retinal locations up to 10.0 deg along the horizontal
      meridian. We found that stereoscopic depth discrimination thresholds, as a
      function of distance from the horopter, increased in an exponential manner
      irrespective of spatial frequency. Stereo-thresholds also increased as a function
      of retinal eccentricity, however, the rate of increase depended on the spatial
      frequency composition of the stimuli. Best stereo-thresholds for stimuli composed
      of low spatial frequencies remained relatively invariant for retinal
      eccentricities up to 10.0 deg, while thresholds for the high spatial frequency
      stimuli increased with eccentricity.

PMID- 7571469
TI  - Modelling the increase of contrast sensitivity with grating area and exposure
      time.
AB  - We extended the contrast detection model of human vision to temporal integration
      by taking into account the effect of exposure duration on contrast sensitivity
      for stationary gratings. The extended model thus comprised: (i) low-pass
      filtering due to the optical modulation transfer function of the eye; (ii) high
      pass filtering (lateral inhibition) due to the neural modulation transfer
      function of the visual pathways; (iii) addition of internal neural noise; and
      (iv) detection by a local matched filter whose efficiency for gratings decreased
      with increasing area and exposure duration. To test the model we measured
      binocular contrast sensitivity in foveal photopic vision as a function of
      exposure duration and area for sinusoidal gratings with equiluminous surround at
      spatial frequencies of 0.25-16 c/deg. In agreement with the model, contrast
      sensitivity at all grating areas first increased in proportion to square root of
      t when exposure duration (t) was shorter than critical duration. Thereafter the
      increase saturated and contrast sensitivity became independent of exposure time.
      Critical exposure duration was found to be independent of grating area but
      increased with spatial frequency. Similarly, at all exposure durations contrast
      sensitivity first increased in proportion to square root of A when grating area
      (A) was smaller than critical area. Thereafter the increase saturated and
      contrast sensitivity became independent of area. Critical area was found to be
      independent of exposure duration but decreased with increasing spatial frequency.
      The extended model explained 95-97% of the total variance of our contrast
      sensitivity data at the spatial frequencies studied. Our results also mean that
      spatial and temporal integration processes are mutually independent and thus area
      and time are separable variables in the detection of stationary gratings.

PMID- 7571470
TI  - Illusory localization of stimuli flashed in the dark before saccades.
AB  - A photic stimulus flashed just before a saccade in the dark tends to be
      mislocalized in the direction of the saccade. This mislocalization is not only
      perceptual; it is also expressed by errors of ocular targeting. A particular
      situation arises if the point of light is flashed twice at the same place, the
      second time, just before a saccade. The point of light may appear at two
      different places even though neither the site of its retinal image nor the
      direction of gaze change between the flashes. Experiments were run on five human
      subjects, head fixed in the dark, with flashes repeated at the site of the
      saccade goal or at the initial point of fixation. In both cases, the test
      stimulus was mislocalized. However, its apparent displacement never produced the
      perception of a streak. Streaks were reported only when there was an actual
      stimulus movement on the retina (e.g. by flashing the stimulus during the
      saccade). Mislocalization did not occur if the two flashes were not separated by
      a dark interval. This implies that, as long as a steady stimulus remains
      continually visible, there is no updating of the internal representation of eye
      position assumed to be used for stimulus localization.

PMID- 7571471
TI  - Cortical simple cells can extract achromatic information from the multiplexed
      chromatic and achromatic signals in the parvocellular pathway.
AB  - P cells, which carry both achromatic and chromatic information, are largely
      responsible for achromatic acuity and contrast sensitivity. The P cell achromatic
      information must be separated from the chromatic information to be useful.
      Cortical simple cells are well suited to the extraction of achromatic information
      by spatial bandpass filtering. Bandpass filtering of Type I P cells by cortical
      simple cells yields an achromatic signal with a residual chromatic response. The
      bandpass model makes predictions in accord with existing physiological data and
      explains the role of a heretofore puzzling class of cortical cells, which have
      bandpass tuning for both achromatic and chromatic modulations. The model is shown
      to be related to a previously postulated class of ideal detectors. Finally, the
      model is used to make a number of physiological and psychophysical predictions.

PMID- 7571472
TI  - The effects of afferent stimulation on congenital nystagmus foveation periods.
AB  - Visual acuity in congenital nystagmus (CN) patients is related primarily to the
      duration of "foveation periods", during which the image of the target is
      relatively stationary in the foveal area. Thirteen individuals with CN were
      studied to test the hypothesis that somatosensory stimulation (vibration or
      electrical) of either the forehead or the neck damps CN and improves visual
      acuity. We identified characteristics of the nystagmus waveform that were likely
      to be important in determining visual acuity and combined these measures into an
      "acuity function" (NAFP) that correlated well with visual acuity (r2 = 0.91).
      Statistically significant changes in NAFP were used to assess the effects of
      afferent stimulation; positive effects were found in nine subjects. Vibratory
      stimulation (especially on the neck) was found to be more effective than
      electrical stimulation. CN amplitude reduction alone was neither necessary nor
      sufficient to improve acuity. Foveation duration was the single most important
      factor determining acuity. Based on our findings, afferent stimulation should be
      considered as an alternative or additional treatment to improve visual acuity in
      CN patients.

PMID- 7571473
TI  - The electroretinographic diagnosis of the incomplete form of congenital
      stationary night blindness.
AB  - Fifteen patients with the incomplete form of congenital stationary night
      blindness (iCSNB) were reviewed to better characterize their electroretinographic
      (ERG) findings in view of differential diagnosis with other retinal conditions
      also presenting with negative bright-flash ERG responses. In all 15 patients, in
      dark-adapted conditions, the bright-flash ERG response had a normal a-wave
      followed by a subnormal b-wave. Oscillatory potentials (OPs) observed on the
      ascending limb of the b-wave, although delayed in implicit time, were of large
      amplitude. The response to a long-wavelength stimulus showed cone-related
      components and some well-delineated OPs. On the other hand, the photopically
      elicited cone responses were strongly abnormal, with a subnormal a-wave followed
      by a barely recordable b-wave. No OPs could be elicited under photopic
      conditions. The cone related components and the OP characteristics clearly
      distinguish iCSNB from the complete form of CSNB and other retinal conditions
      presenting with minimal fundus abnormalities but with negative bright-flash ERG
      responses, such as found in Duchenne muscular dystrophy and Aland Island eye
      disease. The severely abnormal post-synaptic components in the photopic
      recordings contrast with the well-differentiated cone activity evoked in scotopic
      conditions. We propose a cone system that does not respond optimally under the
      normal operating range (photopic) but rather under mesopic or scotopic
      conditions. In spite of the severe cone-ERG deficits, visual acuity was only
      slightly reduced. We propose that the defect, which interferes marginally with
      the neuronal flow of information, lies in the structures responsible for the
      building of the b-wave.

PMID- 7571474
TI  - Health of our nation's children.
AB  - This report describes the health of children 17 years of age and under in the
      United States. The report discusses overall health status, prevalence of
      psychological disorders, access to health care and rates of health care
      utilization, characteristics of other family-controlled health variables, and
      family structure as it relates to health. All estimates are shown according to
      age of child as well as selected demographic and socioeconomic characteristics of
      the family and health characteristics of the child. Particular attention is paid
      to age-, race-, and income-related disparities in the health of children.
      Estimates are based on data from the 1988 National Health Interview Survey on
      Child Health.

PMID- 7571475
TI  - Health aspects of pregnancy and childbirth: United States, 1982-88.
AB  - Statistics collected in 1988 are presented on the timing of the first prenatal
      visit, the source of prenatal care, smoking and alcohol use during pregnancy, low
      birthweight, and how delivery was paid for. The data are shown by race and
      characteristics of the mother and the pregnancy. Trends between 1982 and 1988 are
      also presented.

PMID- 7571477
TI  - [Morphologic findings in liver tissue in chronic active hepatitis B after
      seroconversion from HBeAg to anti-HBe].
AB  - Replication of the virus is in the majority of patients with chronic hepatitis B
      associated with permanent activity and progression of the inflammatory process.
      The change of the virus to the latent stage expressed by seroconversion of HBeAg
      to anti-HBe leads to a significant repression of inflammatory changes and has a
      favourable impact on the course of the disease. The morphological changes in the
      hepatic tissue after spontaneous seroconversion or after interferon treatment
      were investigated in specimens of needle biopsy in 18 patients with active
      chronic hepatitis B. In 10 of them the diagnosis of chronic hepatitis was
      confirmed by biopsy in the stage of replication of the virus. During the
      subsequent time interval after seroconversion of HBeAg, incl. two instances where
      interferon was administered, in the tissue of 14 HBsAg positive patients
      regression of inflammatory changes was apparent, in particular a lower incidence
      of piecemeal necroses. The regular finding of periportal and septal fibrosis in
      these patients is probably associated with a longer course of chronic active
      hepatitis and late spontaneous or therapeutically induced seroconversion of
      HBeAg. In one man, treated with interferon, morphological examination revealed
      one month after seroconversion of HBeAg an acute exacerbation of the disease. In
      another three patients, who at the time of the bioptic examination were HBsAg
      negative, in the hepatic tissue minor silent periportal and septal fibrosis
      persisted.

PMID- 7571478
TI  - [Levels of endogenous plasma cortisol in patients with rheumatoid arthritis and
      other diffuse connective tissue diseases].
AB  - The authors tried to obtain information on levels of endogenous plasma cortisol
      in patients with rheumatoid arthritis and other diffuse connective tissue
      diseases, in particular systemic lupus erythematosus. Endogenous cortisol was
      assessed by radioimmunoanalysis at 8 a.m. and 4 p.m. If the sum of the morning
      and afternoon values reached the level of 280 nmol/l (sum of the lowest still
      normal values), they considered the daily cortisol secretion still normal. In a
      group of 30 patients who did not have glucocorticoid therapy the authors found
      only in one patient a lower daily endogenous cortisol secretion. In 117 patients
      with a relatively severe course of rheumatoid arthritis where small doses of
      corticoids (equivalents of 5-10 mg Prednisone) were administered for prolonged
      periods, a reduced daily secretion of endogenous plasma cortisol was recorded in
      almost 40%. Repeated examinations made in 13 subjects with rheumatoid arthritis
      revealed relatively frequent differences in values of endogenous plasma cortisol.
      In rare instances extremely low plasma levels of endogenous cortisol were found.
      Similar results as in rheumatoid arthritis, although assessed in a relatively
      small number of probands, were obtained by the authors also in patients with
      other diffuse connective tissue diseases, in particular those with systemic lupus
      erythematosus. Those patients had for prolonged periods roughly double doses of
      corticoids as compared with patients with rheumatoid arthritis. During repeated
      examinations the endogenous plasma cortisol levels varied also. The authors are
      aware that from the assembled results it is so far not possible to draw any
      definite conclusions and that further investigations are needed which will test
      the impact of endogenously produced corticoid.

PMID- 7571476
TI  - [24-hour effectiveness and tolerance of perindopril (Prestarium), an ACE
      inhibitor, in the treatment of mild to moderate hypertension. A 1-year Czech and
      Slovak study].
AB  - This one-year open study conducted in two centres investigated the 24-hour
      effectiveness of the ACE inhibitor perindopril in the treatment of 31 patients
      with mild or moderate hypertension. The investigation evaluated the so-called
      "through" effect, i.e. the effect of the drug at the end of the 24-hour dosage
      period. Monotherapy with perindopril (4 mg or 8 mg administered once a day) led
      to normalization of the diastolic pressure to values lower than 90 mmHg in 48% of
      the patients, and a combination of perindopril with hydrochlorothiazide produced
      this effect in another 38% of patients. Treatment thus was able to normalize the
      diastolic blood pressure in 86% of patients. The mean decline of systolic
      pressure in a recumbent position was 17.6 mmHg and 13 mmHg for diastolic pressure
      assessed in a recumbent position 24 hours after ingestion of the drug. The
      reduction of blood pressure achieved after three months treatment persisted for
      the whole year. In 93% of the patients the diastolic pressure was at the end of
      one year lower than 95 mmHg. The drug was very well tolerated and in none of the
      patients the treatment had to be discontinued because of undesirable side
      effects. Perindopril is a significant contribution to the spectrum of drugs used
      in the treatment of hypertension because of its 24-hour effectiveness and very
      good tolerance.

PMID- 7571481
TI  - [Dissecting aortic aneurysm combined with hepatorenal syndrome].
AB  - The authors present a case of a dissecting aneurysm of the aorta type A which
      affected also the insertions of visceral and renal arteries, and in addition to
      renal ischaemia and impaired renal function caused also ischaemia of the liver
      parenchyma with a rise of transaminases and bilirubin. This led to temporary
      hospitalization at the infectious department where the patient was referred to
      rule out hepatitis. In the discussion the authors draw attention to the
      pathogenesis, differential diagnosis and contemporary therapeutic methods of the
      disease.

PMID- 7571479
TI  - [Cytomegalovirus antibodies: review of results of repeated examinations in 208
      hemodialyzed patients].
AB  - Within the framework of prevention of cytomegalovirus (CMV) transmission from
      infected kidney donors to non-infected recipients the author investigates as a
      matter of routine latent CMV infection by assessing the presence of serum IgG
      against pp150 CMV. Antibodies against this phosphoprotein of the viral matrix are
      found in more than 80% of haemodialyzed patients, i.e. potential recipients of
      kidneys (in our group 168 of 208 patients). During repeated examinations of 168
      patients, positive as regards IgG against pp150 CMV, the author observed in 18
      (11%) a temporary change to negativity. At the time of absence of serum IgG
      against pp150 CMV, however, in all patients except one serum IgG and/or IgG
      against some of the CMV antigen spectrum was found in the fibroblasts infected
      with cytomegalovirus. Specific IgM is an indicator of a change of the CMV
      infection from the latent to the active phase. The temporary loss of IgG against
      pp150 CMV may be an associated phenomenon.

PMID- 7571480
TI  - [Changes in platelet function in patients with arterial hypertension].
AB  - The authors examined some indicators of platelet activity in patients with
      hypertension stage II (according to WHO). They revealed an increased platelet
      activity which was manifested by an increased concentration of platelet factor 4
      (50.2 +/- 28.2 ng/ml) and thromboxane B2 (49.9 +/- 20.1 pg/ml) in plasma. The
      increase of indicators of platelet activation associated with hypertension is a
      molecular marker of activation of haemostasis and according to data in the
      literature it is an indicator of vascular complications in hypertension. It is
      not clear whether the increased platelet functions in hypertension is primary or
      an induced change.

PMID- 7571482
TI  - [Pleural effusion in plasmacytic leukemia].
AB  - Multiple myeloma affects predominantly osseous spaces and the close vicinity of
      bones. A plasmacellular exudate is rare. The authors describe the course of
      plasmacellular leukaemia in a 68-year-old female patient where the first symptom
      of the disease was anaemia and a dextrolateral pleural exudate with a cytological
      finding of plasma cells. The exudate disappeared after the first cycle of
      chemotherapy and intrapleural administration of cytostatic. After the third cycle
      of chemotherapy remission of the disease was recorded which was, however, short.
      After three months' remission (six months after establishment of the diagnosis)
      the disease exacerbated violently, the dextrolateral exudate reappeared and
      gradually the insufficiency of the infiltrated bone marrow increased. The patient
      died one month after the relapse of the disease. The finding of a plasmacellular
      exudate must be considered the sign of a very poor prognosis and in that case
      very aggressive treatment is indicated.

PMID- 7571483
TI  - [Successful treatment of agranulocytosis caused by carbimazole using recombinant
      granulocyte-macrophage colony stimulating factor].
AB  - The authors describe a patient with hyperthyroidism who developed after three
      weeks' treatment with carbimazole agranulocytosis and the condition was
      complicated by septic shock. The authors used for treatment in addition to
      antibiotics and corticoids, for the first time in their practice, human
      recombinant granulocyte macrophage colonies stimulating factor (rHuGM-CSF) which
      produced a very favourable effect. In the meantime the patient was prepared for
      goitrectomy, operated and discharged in a satisfactory condition to have
      ambulatory treatment.

PMID- 7571484
TI  - [Treatment of esophageal motility disorders with acupuncture of the ear
      (preliminary report)].
AB  - Impaired motility of the oesophagus is relatively frequent in patients with
      functional blocks of the cervical spine. The patient does not always realize
      oesophageal dysmotility. Auricular acupuncture focused on reflex relations seems
      to be a useful therapeutic procedure.

PMID- 7571485
TI  - [Ventricular tachycardia in non-ischemic heart disease].
AB  - Ventricular tachycardia (VT) is found usually in patients with structural heart
      disease. Its symptomatology depends on haemodynamic manifestations. ECG criteria
      for the diagnosis of VT are known. For the classification of VT we use
      morphological criteria (monomorphous and polymorphous), duration of arrhythmia
      (non-and sustained VT) and the pathomechanism of VT (re-entry, increased
      automation and triggered activity). The clinical impact of VT and the therapeutic
      approach depend to a great extent on the basic disease. The therapeutic results
      and prognostic estimates assembled in ischaemic heart disease cannot be
      mechanically applied in non-ischaemic heart disease. The authors mention the
      prevalence of VT and the approach to its treatment in dilatative cardiomyopathy,
      in prolapse of the mitral valve, in hypertrophic cardiomyopathy, in
      arrhythmogenic right ventricular dysplasia and in patients with a "normal" heart.
      Only collection of the necessary data and their analysis will help us to achieve
      better therapeutic results. In the treatment authors focus attention first of all
      on the pharmacological approach. They emphasize the need of thorough and
      comprehensive examination of the patient, draw attention to proarrhythmia. In the
      prevention of relapses of VT most frequently beta-blockers and amiodarone are
      used (either alone or combined).

PMID- 7571486
TI  - [Pathophysiology and clinical aspects of dissecting aortic aneurysms].
AB  - Dissecting aneurysms of the aorta are among the most dangerous acute conditions
      in medicine. Their incidence is rising in recent years. The pathogenesis of
      vascular aneurysms is not completely clear. In the submitted paper the authors
      discuss the most important factors (atherosclerosis, hereditary, metabolic,
      mechanical, haemodynamic, nutritional) responsible for the development and growth
      of an aneurysm as well as for the progressing dissection. The authors compare the
      most important diagnostic methods from the aspect of sensitivity and specificity.
      In the conclusion they give a brief account of dissecting aneurysms at the IVth
      Medical Clinic University Hospital Kosice during the period from 1989 to November
      1994.

PMID- 7571487
TI  - [Cardiomyopathies and myocarditis].
AB  - The authors discuss recent findings regarding cardiomyopathies, assembled
      recently due to the association of clinical and experimental cardiology. The main
      attention is paid to the pathogenesis of cardiomyopathies from the aspect of
      metabolic disorders of the heart muscle at the cellular and subcellular level.
      The differential diagnosis in relation to myocarditis is still a serious problem
      in cardiology: acute myocarditis is not a myocardiopathy, there exists, however,
      a close relationship between viral myocarditis and the development of dilatation
      cardiomyopathies. Echocardiography is one of the most important diagnostic
      examinations.

PMID- 7571488
TI  - [Treatment with nonsteroidal anti-inflammatory agents in the aged].
AB  - Some 13--33,7% old people use non-steroid antiphlogistics. The authors mention
      undesirable effects, their incidence being higher in advanced age, as well as
      differences between effects of different non-steroid antiphlogistics.

PMID- 7571489
TI  - [Malnutrition in chronic obstructive bronchopulmonary diseases].
AB  - Malnutrition occurs in 23-70% of patients with chronic obstructive pulmonary
      disease and appears to be an independent factor connected with poor prognosis.
      Malnutrition stems from a long-term negative balance of energy and nutrients.
      That is caused by hypermetabolism, with possible role of an increased thermic
      effect of food, and probably by (at least intermittently) a limited intake of
      food. The adverse effect of malnutrition may be mediated by a decreased
      respiratory muscle strength but also by other mechanisms (electrolyte disorders,
      disturbed respiratory control, immunosuppression). In these patients,
      realimentation may be difficult to achieve, especially on the out-patient basis.
      However, with an increased effort of the health professionals and a good
      compliance of the patients, a substantial improvement is feasible, which might in
      turn improve the patients' prognosis.

PMID- 7571490
TI  - [New findings on the classification, diagnosis and therapy of primary
      gastrointestinal lymphomas].
AB  - Based on available recent data from the literature the authors review recent
      findings pertaining to the etiopathogenesis, immunology, clinical manifestations
      and treatment of primary gastrointestinal lymphomas. From the pathogenetic aspect
      in particular the close association with infections and immune disorders in
      various portions of the gastrointestinal tract is important. In their review the
      authors draw attention to new aspects of the histological and immunological
      classification of these tumors, in particular as far as definition of lymphomas
      of the MALT-system is concerned. They evaluate also data from their own group of
      83 patients with regard to the incidence and site of the disease. In the
      conclusion they draw attention to the importance of some new therapeutic
      approaches, incl. antibacterial treatment.

PMID- 7571491
TI  - [The status and main trends of the development of a medical supply system under
      current conditions].

PMID- 7571493
TI  - [The organization of the work of military forensic medical experts in identifying
      the dead in an area of armed conflict].
AB  - The authors summarize the experience of work of legal physicians in
      identification of servicemen who have perished on the territory of Chechnya. The
      article contains data concerning the methods of classification of non-identified
      cadavers in three identification groups and gives a scientifically substantiated
      system of pre-identification preparation of cadavers. A number of problematic
      questions which need its further solution are raised.

PMID- 7571492
TI  - [The organizational characteristics of psychiatric care in modern local wars and
      armed conflicts].
AB  - In order to improve the organization of psychiatric care in modern local wars and
      armed conflicts the authors propose to follow a number of basic principles: to
      bring psychiatric care closer to the forward combat zone; to realize prognostic
      triage throughout casualty staging; to assure in maximum the return of minimally
      wounded and sick to their ranks directly from the forward zone; to unify the
      approaches to diagnosis, treatment and rating evaluation of psychic disorders; to
      observe the sequence and succession in psychiatric care; to realize recovery
      measures throughout all stages.

PMID- 7571494
TI  - [The problems of integrating therapeutic and diagnostic work].

PMID- 7571496
TI  - [The early diagnosis of systemic connective tissue lesions at the polyclinic
      stage].

PMID- 7571495
TI  - [HIV infection in servicemen (the work experience of a specialized hospital
      department)].

PMID- 7571497
TI  - [The leaders of the fleet medical service in World War II].
AB  - The hard trials experienced by the Navy and its medical staff during the Great
      Patriotic War were caused by the emergency situation which was accompanied with a
      sudden disarrangement in the deployment of medical assets. Serious shortages were
      revealed at that perios as far as organization of mass casualty staging from
      blockaded Navy bases is concerned. But when the combat experience was obtained
      the activities of Navy medical service were improved. Physicians of different
      specialties,--administrative officers, surgeons, internists, epidemiologists, etc
      -have enhance their professional skills. The corps of Senior medical specialists
      had played a great role in organization of medical support of fleets and
      flotillas, in the development of theory and practice of national navy medicine.
      The positive results of the activities of Navy medicine were also obtained by
      dedicated work of the medical service leaders of Fleets: F. F.Andreev, G.
      A.Babkin, V. R.Bauder, S. N.Zolotukhin, A. M.Zotov, M. N.Kravchenko, M.
      Ia.Krivoshein, A. G.Nazarov, A. V.Smol'nikov, I. A.Tolkachev. Navy physicians
      succeeded in providing an opportune medical care to seamen in the years of war.

PMID- 7571498
TI  - [The efficacy of physiotherapeutic methods in the combined treatment of duodenal
      peptic ulcer].

PMID- 7571499
TI  - [Modern disinfectant agents].

PMID- 7571500
TI  - [The body functional indices of those maintaining ionizing radiation sources].

PMID- 7571504
TI  - [The problems of sanitary toxicological monitoring in the armed forces].

PMID- 7571501
TI  - [The characteristics of the spinal trauma in catapulted pilots].
AB  - The article discusses the peculiarities of spinal fractures in catapulted pilots:
      mechanism of fracture--indirect axial load in combination with front or front
      lateral bending; morphological picture--wedge-shaped compression fracture of
      vertebral body; type of fracture--stable; clinic peculiarities--scanty clinic
      picture as a rule; localization--mid-thorax section and thoracolumbar zone;
      number of vertebrae affected--1 as a rule. Diagnostic and treatment
      recommendations are enclosed. The author also deals with a phenomenon which
      accompanies the emergency abandon of an aircraft--microlesion of spongy osseous
      tissue of vertebrae without fracture signs under the influence of shock overload,
      which later can be the reason of degenerative and dystrophic diseases of spine.
      Preventive and medical measures are described which assure an adequate
      rehabilitation of functional state of spine.

PMID- 7571502
TI  - [The functional status of sailors from different job groups].
AB  - Taking into account different professional duties and peculiarities of combat
      training all servicemen are working in different conditions that obviously
      reflects on their functional state. Submarine personnel with its prolonged stay
      in technogenic environment is exposed to continuous stresses, basically of
      emotional genesis, which is aggravated by hypokinesia and hypodynamia in the
      conditions of sensor deprivation and chronostress. As for skin divers who are
      working in natural environment, they are basically withstand periodic and short
      time loads with domination of physical component. During these studies 17
      submariners and 9 frogmen (age 19-24) were examined in the conditions of their
      routine combat training in the North Europe region. It was found out that
      functional state of divers was considerably better than of submariners. It proves
      the detriment influence of specialized adaptation and also demonstrates the
      differences in functional state of seamen from different professional groups.

PMID- 7571505
TI  - [The status and outlook of outfitting the military medical service with the
      technical materiel for prophylactic health purposes].

PMID- 7571506
TI  - [The missions of the medical service of the Army and Navy in accomplishing
      epidemiological health surveillance in support of radiation safety].

PMID- 7571503
TI  - [The 30th anniversary of the Military Medicine Department of the Siberian State
      Medical University].

PMID- 7571507
TI  - [A method for predicting infectious morbidity].

PMID- 7571508
TI  - [The epidemiological surveillance of natural-focus infections in medical service
      practice].

PMID- 7571509
TI  - [The current status of the problem of cholera epidemiology and the improvement in
      prophylactic measures among the troops].

PMID- 7571510
TI  - [The epidemiological aspects of chronic viral diseases of the liver].
AB  - The article discusses epidemiological problems of chronic viral hepatic diseases
      making a thorough analysis of etiological structure of chronic cirrhosis and
      cancer of liver, describing its social and epidemiological significance, and also
      its epidemiological danger for other people. The author puts forward strong
      arguments for the existence of intensive and latent epidemic process of chronic
      hepatitis in the families, human contingencies and medical establishments. The
      article makes a scientific substantiation of a system of sanitary-epidemiological
      supervision and antiepidemic measures in the sites of chronic viral hepatic
      diseases.

PMID- 7571511
TI  - [Prospective trends in the planning optimization of the activities of the
      epidemiological health institutions of the Army and the Navy].
AB  - In the modern stage of the development of medical service the planning of
      preventive measures must be accompanied with prognostication and economic
      estimation of the expenses, as well as by veritable definition of the malady. The
      improvement of methodological approaches in planning is an important part of a
      system of prophylaxis of infectious diseases. The complex method of the analysis
      of epidemiological situation must provide for more effective fulfillment of tasks
      using short and long-term plans of prophylactic works.

PMID- 7571513
TI  - [The diagnosis of chlamydiosis and urogenital mycoplasmosis by using the
      polymerase chain reaction].

PMID- 7571512
TI  - [The prospects for the development of viral vaccines].

PMID- 7571516
TI  - [Medical support for the troops in the Berlin Offensive Operation].

PMID- 7571514
TI  - [Improvement in microbiological studies to objectivize epidemiological health
      surveillance].

PMID- 7571515
TI  - [Hospital hygiene and the medicosocial problems of preserving human health in
      medical institutions].
AB  - The article contains data concerning nosocomial malady and the efficiency of
      preventive measures. The authors analyse the reasons and the conditions of the
      increase of hospital-acquired diseases, and show the significance of hospital
      hygiene.

PMID- 7571517
TI  - [Near Staraia Russa (from the notes of a military physician)].

PMID- 7571518
TI  - [The 160th anniversary of the District Military Hospital of the Leningrad
      Military District].

PMID- 7571519
TI  - [A quarter of a century for the College of Military Pharmacists].

PMID- 7571520
TI  - [The theory and practice of epidemic control support for armed forces personnel].
AB  - Taking into account the theory of self-regulation of parasitic systems the
      authors analyse the basic trends of reformation of antiepidemic work in the Army
      and Navy. The article discusses the necessity of a wide use of methods of
      epidemiological diagnostics, social-hygienic monitoring, screening tests on
      pathogenicity of actual infectious agents and immune resistance of personnel. It
      will be possible to make a transition to a differentiated prophylaxis and
      struggle with actual infections taking into account the local territory, time and
      risk groups on the basis of principles of epidemiological supervision which is
      substantiated by the theory of self-regulation of parasitic systems. It will make
      it possible to optimize the antiepidemic work, to increase the quality and the
      effectiveness of antiepidemic measures, and thus, obtain best economic results.

PMID- 7571522
TI  - [Viral hepatitis C. Personal experience with diagnostic, monitoring and
      epidemiologic studies].
AB  - In the period from 1991 to 1993, 18 patients with the acute viral hepatitis type
      C were treated and followed up--13 men and 5 women, the average age of 42 years.
      The group of 6 patients (4 men and two women) with the "old" proven liver
      cirrhosis, whose etiology was unknown for 20 years, was analyzed. The
      investigations showed that the acute viral hepatitis type C usually began with
      the mild subjective disorders. The half of the patients did not have either
      jaundice or hepatomegaly, only half of them recover, and the first cases of
      cirrhosis could have been expected almost as early as a year after the beginning
      of illness. The developed liver cirrhoses remained compensated for years. About
      58% of patients got infected parenterally, and the rest of them could have gotten
      infected in other manner. ELISA test showed great reliability in proving the
      antibodies against the viral hepatitis type C in the confirming the diagnosis of
      illness.

PMID- 7571521
TI  - Relationship between early neuroendocrine response and severity of war injury
      according to the Red Cross Classification.
AB  - The hypothesis that neuroendocrine response to military gunshot/missile (MG/M)
      wounds reflect the severity and type of wounds given by the Red Cross Wound
      Classification (RCWC), has been tested on 82 casualties of war in former
      Yugoslavia. Adrenaline (A), noradrenaline (N), Cortisol, triiodothyronine (T3),
      testosterone (TES) and prolactin (PRL) levels have been measured in blood samples
      taken on admission (2-18 hr after wounding) at Military Medical Academy.
      Neuroendocrine response to MG/M wounds has clearly reflected severity but not the
      type of wounds and it has been bidirectional, i.e. A, NA and cortisol levels
      positively related to, while T3 and TES levels were negatively related to
      severity of MG/M wounds. With regard to high compatibility between RCWC and
      Injury severity score (ISS) and the fact that magnitude of the neuroendocrine
      response is related to severity given by RCWC we have concluded that the RCWC is
      a good method of grading wound severity on the battlefield.

PMID- 7571523
TI  - [Chronic knee instability--arthroscopic analysis].
AB  - Knees in 150 patients with the old disruption of the anterior cruciate ligament
      (ACL) and a certain degree of anterolateral rotational instability have been
      arthroscopically analyzed. The complete old disruption of ACL has been found in
      130 (86.6%) patients, and a partial one in 20 (13.4%) patients. The degenerative
      changes of the inner femoral condylus have been present in 79 (52.6%) and of
      lateral femoral condylus in 14 (9.3%) patients. In 35 (23.3%) patients there has
      been the simultaneous disruption of both menisci. The isolated disruption of
      medial meniscus has been found in 44 (29.3%), and of the lateral one in 43 (28%)
      patients. The knee with disruption of meniscus has been found in 122 (81.3%)
      patients.

PMID- 7571524
TI  - [Surgical treatment of toxic adenoma].
AB  - Sixty eight patients with toxic adenoma (TA) operated on in the period 1985-1992,
      were analyzed. The manifestation of hyperthyroidism in TA (in 55.88%)
      significantly depended on the gender of the patients (68.42% in men and 51.02% in
      women) and on the size of node. In nodes larger than 5 cm in diameter
      hyperthyroidism appeared in 76.92% of patients and in none with the nodes smaller
      than 2 cm. The degenerative changes in the nodes depended on pathohystological
      type of adenoma, and not on the size of nodes. On patohystological examination
      three carcinomas were found in TA, two papillary and one follicular. The surgical
      treatment of TA was the optimum way of treatment--the therapy of choice. Along
      with fast, complete and clear effects, the minimum percentage of complications
      (4.41%) developed that were mild and of short duration. The enucleation of nodes
      with capitonnage was absolutely sufficient in the operative treatment.

PMID- 7571525
TI  - [Treatment of pneumonia under hospital conditions].
AB  - A random sample of 24 patients affected by bacterial pneumonia has been
      investigated whether their illness is treated etiologically. The agents have been
      detected from the endoscopically obtained samples of blood or chest punctate
      (percutaneous needle aspirate--PNA) and their sensitivity to antibacterial drugs,
      used in our institution, have been investigated. The obtained results have been
      compared to the empirically applied drugs. In only three patients the first given
      drug corresponded to the later obtained finding of the agent's sensitivity and in
      one patient third and the fourth drug has been adequate. The rational initial
      therapy has been proposed on the basis of investigation of the sensitivity of the
      bacterial pneumonia agents.

PMID- 7571526
TI  - [Epidemiologic characteristics of hemorrhagic fever with renal syndrome in Serbia
      1979-1992].
AB  - Data on the incidence and deaths of hemorrhagic fever with kidney syndrome (HFKS)
      in Serbia 1979-1992 were analyzed. Mostly sporadic cases of illness were
      registered, but for two years it was epidemy in 1986., with 34 and in 1989., with
      42 ill. The morbidity rate was between 0.01 and 0.72 /10000 (on average 0.16
      /0000). Most often men (72.7%) between 20-39 years old, industrial workers
      (33.3%) got affected, whose place of living was in the rural environment. The
      lethality rate was high--7.6%, in epidemies 11.8%, and during sporadic occurrence
      1.8%. The ill were registered during the whole year, but the characteristic
      season of illness was May--September with 76.3% of the total number of the ill.
      The topographic distribution of the ill showed that the greatest number of the
      ill with HFKS (45.8%) occurred in three counties in Serbia--in Ivanjica, Cacak
      and Lucani.

PMID- 7571527
TI  - [Clinical manifestations of infectious erythema in adults].
AB  - The infectious erythema is usually childhood disease associated with rash and
      caused by parvovirus B19. At the beginning of 1993., at the Clinic for infectious
      and tropical diseases of the Military Medical Academy 36 patients were treated
      for this disease, the average age 21 years. The prodromal phase of illness lasted
      approximately 2.9 days, the elevated temperature 5.2 days, and 17 patients had
      temperature above 39 degrees C. The rash was usually maculo-papullous and lasted
      about 6 days. Four patients had the recurrence of rash. The polyarthralgia
      appeared for short in six patients and in one patient lasted longer than 4
      months. The mild anemia during infectious erythema was observed in 18 patients.
      IgM antiparvo B19 antibodies were proven in serum in 91.7%, and IgG antibodies in
      58.3% of patients.

PMID- 7571528
TI  - [Anti-pain effect of salmon calcitonin in bone metastases of malignant tumors
      with the exception of breast and prostatic carcinoma].
AB  - In 16 patients with pain caused by diffuse osteolytic or osteoplastic-osteolytic
      metastases, salmon calcitonin was used as pain relieving treatment. All patients
      were pretreated with opiate type analgesics without a satisfactory effect. In 2
      patients it was possible to withdraw completely previous opiate intake. In most
      of the patients the analgesic effect of salmon calcitonin consisted in decrease
      of pain with identical or decreased intake of opiate type analgesics. In 3
      patients the pain relieving treatment with salmon calcitonin completely failed.
      Our investigation seems to demonstrate that there is a subpopulation of patients
      with bone metastases, resistant to opiate type analgesics, in which salmon
      calcitonin can be administered as an additional useful pain relieving drug.

PMID- 7571530
TI  - [Pathophysiology of injuries and regeneration of peripheral nerves].

PMID- 7571531
TI  - [Percutaneous poisoning with sulphur mustard. Prevention, decontamination and
      therapy].

PMID- 7571529
TI  - [Praziquantel in the treatment of human echinococcosis].
AB  - In the period from 1989 to 1993, 73 patients with Echinococcus granulosus cysts
      were treated by prazyquantel. To differentiate cysts tests of indirect
      immunofluoroscence and hemagglutination were used. The tests were performed
      during and after the completed treatment. During the treatment three patients
      were excluded so that 70 patients completed the treatment. Fifty five (78.9%)
      patients were treated only with drug with a success of 67% (37 patients). The
      preventive treatment, due to cyst perforation, was performed in 3 (4.3%)
      patients. Dissemination of illness occurred in no patients. Twelve (16.8%)
      patients were treated surgically. The parasite was not alive in 7 (58.5%)
      patients. The vitality of the parasite was controlled by microscopic examination
      of protoscolex and by their inoculation into rats of AO strain. The total success
      of treatment was 67.4% (47) of patients. In two patients the treatment was
      discontinued due to allergic manifestations. In our opinion, the drug treatment
      was the therapy of choice in patients with Echinococcus granulosus. It should be
      given prophylactically, preoperatively, to sterilize the cyst and also as a
      curative treatment.

PMID- 7571532
TI  - [Larva currens--characteristic manifestations of strongyloidosis].

PMID- 7571533
TI  - [Acute abdomen caused by torsion of the omentum--case report].

PMID- 7571534
TI  - [A psychoanalytic approach to cases of anorexia nervosa].

PMID- 7571536
TI  - Histopathological evaluation of the carbon fibers application for the
      substitution of the anterior cruciate ligament--an experimental study on dogs.
AB  - The application of allograft-carbon fibers on the experimental group of 15 dogs
      (German Shepherd race) was histopathologically investigated after the artificial
      lesion of anterior cruciate ligament (ACL). In definite time intervals (1, 2, 4,
      6 months) pathoanatomic and histopathologic findings were analyzed and the
      proliferation of new connective tissue of predominantly elastic type, between
      carbon fibers was observed. Beside the lymphocyte infiltration around torn carbon
      fibers giant cells of a foreign body type were found, and on the surface the
      epithelium similar to synovial was observed. It was concluded that carbon fibers
      could not be considered as the ideal artificial ligament.

PMID- 7571535
TI  - [Dopaminomimetic psychosis].

PMID- 7571537
TI  - [Therapy of middle ear injuries caused by explosive devices].
AB  - Forty nine wounded with the explosive injury of the middle ear were treated. The
      largest number of injuries were ruptures of the ear drum (79.35%), followed by
      the break of the ossicular chain (15.87%) and the fractures of the mastoid, along
      with the paralysis of the facial nerve (4.77%). In therapeutic procedure the
      reposition and connection of the eardrum parts and 'patch' technique were
      performed, and in case of perforation persistence longer than four months
      myringoplasty was done. Injuries of the auditory bones were solved by
      ossiculoplasty, and injuries of facial nerve by decompression and neuro suture.
      In 66% spontaneous healing of rupture occurred and the ossicular chain was
      successfully fixed in 80% of injuries while the reparation of the facial nerve
      was partially achieved. The acute secondary infection developed in 18% and the
      chronic otitis in 10% of cases. The early reposition of the eardrum rupture is
      recommended due to infection prevention of the middle ear and in order to
      stimulate the spontaneous improvement, while the surgical treatment is
      recommended in cases with persistent rupture or conductive loss of hearing
      lasting longer than four months.

PMID- 7571538
TI  - [Disorders of olfactory function in penetrating head injuries sustained during
      war].
AB  - Olfactory function was estimated in the group of 37 patients with the penetrating
      war head injury. In 4 (10.8%) patients mutual anosmia was found. In comparison to
      healthy volunteers the injured showed worse performance on the level of the
      tested olfactory parameters. In 9 (24.3%) patients the offered smells were sensed
      as very unpleasant. The subgroup of patients from Glasgow Coma Scale (GSC) < or =
      8 showed the highest degree of olfactive disfunction. The patients with
      complicated penetrating head injury were less successful at the level of all
      olfactive qualities comparing to those without injury complications. The
      localization of the focal penetrating wound, regardless of the kind of a weapon
      causing the brain injury, was not significantly correlated with the results of
      olfactometry in distinction from hemisphere lateralization of the lesion. The
      recovery of the retested was minimal.

PMID- 7571539
TI  - [Mortality in Serbian males from the most common malignant tumors].
AB  - The frequency and distribution of mortality of men in Serbia caused by the most
      frequent malignant tumors in the period from 1982. to 1991., were shown. Data
      were taken from the Republic Statistic Center. For the evaluation of the
      situation the descriptive epidemiological method was used. In that period men
      mostly died from lung, stomach, prostate, liver, rectum, pancreas, larynx, colon,
      brain and urinary bladder cancer. In the same period the mortality increase was
      observed in lung cancer, rectum, pancreas, colon, urinary bladder, brain, larynx
      and liver. For the cancer of prostate and stomach the decrease of mortality was
      noticed.

PMID- 7571540
TI  - [Delayed-pressure urticaria--analysis of 28 patients].
AB  - Twenty eight patients (18 men and 10 women) with delayed pressure induced
      urticaria were analyzed. The average age was 35.5 years, and the illness lasted 1
      20 years, 4.07 years on average. The spontaneous cessation of illness came in 8
      patients after approximately 5.75 years. In 23 patients there was also a
      classical chronic urticaria. C3, C4, alpha 1 antitrypsin, alpha 2 macroglobulin,
      immunoglobulin IgG, IgA, IgM and IgE were determined for 15 patients and findings
      were within normal limits apart from the moderate increase of IgE in 2 patients.
      Fifteen patients were examined for intestinal parasites and in 3 patients they
      were found. Also, a pathogenetic mechanism of illness was considered: the role of
      histamine, proteinase inhibitors, mediators of the delayed allergic urticaria.

PMID- 7571542
TI  - [Medico-technologic measures for protection of the population during chemical
      warfare in the recent war].

PMID- 7571541
TI  - [Gas-mass spectrometry in the identification and determination of ethanol in
      blood].
AB  - A contemporary analytical method for positive identification and quantitative
      toxicological--chemical analysis of ethanol in blood samples using the methods of
      gas extraction, thermal adsorption/desorption and gas-mass spectrometry, was
      developed. Maximal sensitivity of ethanol detection was 0.27 mmol/l.

PMID- 7571544
TI  - [Modern technologic development and progress in diagnostic radiology. I].

PMID- 7571543
TI  - [Rational basis for development of a treatment program for Parkinson's disease].

PMID- 7571545
TI  - [Treatment of hepatic insufficiency with hepatocyte transplantation and the
      bioartificial liver].

PMID- 7571546
TI  - [Cerebrovascular insufficiency caused by coiling of the internal carotid artery].

PMID- 7571547
TI  - [Solitary retroperitoneal schwannoma (neurilemmoma)].

PMID- 7571548
TI  - [A case of familial multiple sclerosis].

PMID- 7571549
TI  - The fattening of America.

PMID- 7571550
TI  - Issues of control in patients with cancer pain.
AB  - The enhancement of patient control is frequently cited in nursing literature as
      an important area of nursing intervention. In this article, the concept of
      control, from the perspective of the patient with cancer pain, the primary family
      caregiver, and the home-care nurse, is discussed. Lewis identified five types of
      control: processual control, contingency control, cognitive control, behavioral
      control, and existential control. Lewis's typology of control was used as an
      organizing analytical framework, in this study, for interpreting the interview
      responses of each member of the triad. Similarities and differences in the
      perspectives of each member are discussed and examples of interventions that may
      be used to increase control in the management of pain are presented.

PMID- 7571551
TI  - "Nothing to hide and nothing to advertise". Managing disease-related information.
AB  - The purpose of this study was to explore the process of managing disease-related
      information through various developmental stages from the inside perspective of
      those who live with a long-term health condition. The retrospective,
      longitudinal, life history method was used to generate a descriptive theory from
      accounts constructed with 21 informants: 10 adolescents and young adults with
      cystic fibrosis (CF) aged 16 to 25 years, and 11 of their significant family
      members. People chose a specific telling strategy according to the perceived
      ability of the audience to deal with the information and the situational context.
      Four strategies of managing disease-related information emerged: visibility,
      direct telling, silent telling, and concealment. The informants frequently chose
      information management strategies that enabled an ordinary style of living. These
      strategies neither reflect feelings of shame nor of pride, as it is suggested in
      the existing literature. Implications for theory, health care practice, and
      further research are discussed.

PMID- 7571552
TI  - Psychosocial factors influencing weight control behavior of African American
      women.
AB  - The purpose of this descriptive study was to seek directly from college-educated
      African American women factors which they perceived influenced their individual
      weight control behavior, and those that influenced African American women
      collectively. Face-to-face, in-depth interviews were conducted, primarily in
      their homes, with 36 African American women. Thirteen major categories were
      identified. Six factors that influenced the women's individual weight control
      behavior were emotions/feelings, beliefs, life events, self-control, discipline,
      and commitment. Perceived benefits of the behavior and perceived barriers to the
      behavior were influential in determining the attractiveness, the type, and the
      extent of the weight control behavior. Five factors related to the African
      American culture were identified and described by the women. Recognition of
      psychosocial determinants of weight control behavior may enable health
      professionals to design unique interventions relevant to African American women.

PMID- 7571553
TI  - The stress of immigration and the daily lived experiences of Jordanian immigrant
      women in the United States.
AB  - Literature specifically focused on women as immigrants and on the nature and
      quality of the immigrant experience is limited. Similarly, in spite of early Arab
      immigration to the different regions of the world, there is a limited knowledge
      base regarding the dynamics and problems involved in their integration into their
      new society. In this article we describe the lived experiences of Jordanian women
      who immigrated to the United States and the focus is on providing an in-depth
      account of their perceived stressors as related to their immigration experience.
      Thirty Jordanian American women, all wives and mothers with a mean age of 45,
      were interviewed. Three major themes of the sources and contexts of stress
      emerged from the narrative and qualitative data analyses of their responses.
      Women experienced many challenges and stressors surrounding their work in the
      daily living of settling in, in their quest for ethnic continuity, and in their
      attempts to re-create familiarity. Social and health support resources cannot be
      created without careful attention to these themes.

PMID- 7571554
TI  - The Rockefeller agenda for American/Philippines nursing relations.
AB  - The Philippines leads all countries in global nurse emigration. Today, Filipino
      nurses represent over 75% of the foreign nurse labor force recruited to and
      working in American hospitals, most of which are inner-city municipally operated
      institutions with reported shortages of nursing personnel. This article examines
      the historical roots of the American/Philippines nursing relationship more
      generally and the particular role of the Rockefeller Foundation in the 20th
      century emigration patterns and work practices of Filipino nurses. Examination of
      one group of nurse workers enhances an understanding of the ways in which social,
      cultural, economic, and political factors influence broader health care
      decisions.

PMID- 7571555
TI  - Use of the multitrait multimethod (MTMM) to analyze family relational data.
AB  - In this article, the authors propose the logic of the multitrait multimethod
      (MTMM) approach for analysis of data as an alternative solution for examining
      family relational data. Application of the MTMM logic permits the assessment of
      common perspectives shared by all family members and of the unique perspectives
      of individuals. The advantages of using this approach in family research include
      the ability to (a) maintain consistency between systems theory views of family-as
      a-unit, and (b) delineate patterns of agreement, disagreement, or both among
      family members.

PMID- 7571556
TI  - Involving students in advanced practice nurses' and nurse educators'
      collaborative research.

PMID- 7571558
TI  - Argon and YAG laser photocoagulation and excision of hemangiomas and vascular
      malformations of the nose.
AB  - A total of 22 patients--19 children, 3 adults--with a variety of hemangiomas and
      vascular malformations of the nose were treated over a 5-year period. Various
      laser modalities were used. Some lesions could be photocoagulated by the argon or
      the yttrium-aluminum-garnet (YAG) laser. Larger lesions were resected with the
      YAG laser and sapphire tips. Preliminary arteriography with superselective
      embolization was necessary in 1 patient. Total removal was possible in 13
      patients, and no complications or side effects were noted.

PMID- 7571557
TI  - Sea-level physical activity and acute mountain sickness at moderate altitude.
AB  - The effect of previous physical conditioning on young well-conditioned
      mountaineers in relationship to acquiring acute mountain sickness is
      controversial. Data show both increased and decreased effects on the incidence of
      altitude illness. How general tourists at moderate altitudes are affected is
      unknown. To determine the influence of sea-level habitual physical activity on
      the incidence of mountain sickness, we surveyed 205 participants in a scientific
      conference at 3,000 m (9,840 ft). A 36-item questionnaire was distributed to the
      subjects 48 hours after arrival at altitude. Their sea-level physical activity
      (SLPA) was measured by a published and validated instrument that included
      questions about patterns of work, sporting, and leisure-time activities. Acute
      mountain sickness was defined as the presence of 3 or more of the following
      symptoms: headache, dyspnea, anorexia, fatigue, insomnia, dizziness, or vomiting.
      Most of the respondents were male (62%) from sea level (89%) with a mean age of
      36 +/- 8.7 (standard deviation) years (range, 22 to 65). Nearly all (94%) were
      nonsmokers, and 28% had acute mountain sickness. The mean SLPA score was 8.0 +/-
      1.3 (range, 5.1 to 12.0). No statistically significant difference in mean SLPA
      scores was found between those with and without acute mountain sickness (8.1
      versus 7.8), nor in the individual indices (work, 2.5 versus 2.4; sport, 2.9
      versus 2.7; leisure, 2.8 versus 2.7). We conclude that habitual physical activity
      performed at sea level does not play a role in the development of altitude
      illness at moderate altitude in a general tourist group.

PMID- 7571559
TI  - Staphylococcus aureus septic arthritis in patients on hemodialysis treatment.
AB  - We retrospectively reviewed hospital discharge diagnoses of septic arthritis over
      an 11-year period (1982 through 1992) at 3 medical centers; 11 episodes of septic
      arthritis were identified in patients on hemodialysis treatment. Of the 11
      episodes, 9 were caused by Staphylococcus aureus; in 8 of 9, the blood cultures
      were positive for the organism and the infection was monoarticular. Concurrent
      infection of the dialysis access site occurred in 4 cases. Two patients died
      (22%). We postulate that repeated skin trauma and contact with health care
      personnel and facilities result in a high rate of nasal carriage of S aureus and,
      hence, an increased risk of bacteremia with its attendant complications such as
      septic arthritis. The use of mupirocin nasal ointment is reported to eradicate or
      suppress carriage in a high percentage of patients; some studies report that long
      term suppressive therapy reduces the frequency of S aureus bacteremia.

PMID- 7571560
TI  - Prevalence and reversibility of the hepatopulmonary syndrome after liver
      transplantation. The Cleveland Clinic experience.
AB  - To ascertain the prevalence and reversibility of the hepatopulmonary syndrome, we
      reviewed the cases of 98 patients undergoing liver transplantation at the
      Cleveland (Ohio) Clinic Foundation from June 1988 through July 1992 and
      identified 4 patients with clinically recognized hepatopulmonary syndrome
      (prevalence 4%). All 4 patients ultimately had complete reversal of their
      disorder. As reviewed herein, the prevalence of the hepatopulmonary syndrome in
      the current series is lower than in previous reports, possibly reflecting a
      dependence on its clinical recognition in this series rather than the use of
      routine screening tests. This report confirms previous experience that the
      hepatopulmonary syndrome may be reversible after transplantation.

PMID- 7571563
TI  - Guidelines for managing chronic otitis media with effusion.

PMID- 7571561
TI  - Cuba's national AIDS program. The first decade.
AB  - There is a high incidence of infection with the human immunodeficiency virus
      (HIV) in many Caribbean nations. But by 1993 Cuba, with a population of greater
      than 10 million people, had fewer than 1,000 seropositive persons and less than
      200 cases of the acquired immunodeficiency syndrome (AIDS). To investigate Cuba's
      approach to the AIDS epidemic, we visited Cuba, reviewed published statistics,
      spoke with health care officials, interviewed HIV-positive patients, and toured
      medical facilities. Cuba established an extensive HIV surveillance program in
      1983, and more than 15 million HIV antibody tests have been done. The sexual
      contacts of all infected persons are closely observed. A national education
      program is evolving. Since 1986, all known HIV-positive patients have been placed
      in sanitariums, which is the most controversial aspect of Cuba's program. We
      review available information on AIDS in Cuba and describe that nation's attempt
      to prevent the spread of disease. We discuss how the political system and Cuba's
      relative isolation have influenced this approach. Strategies have been developed
      that may be of limited efficacy and would not be acceptable in most Western
      nations.

PMID- 7571564
TI  - Benign positional vertigo.

PMID- 7571562
TI  - Anticoagulation and atrial fibrillation. Putting the results of clinical trials
      into practice.
AB  - The thromboembolic risk of atrial fibrillation varies with the underlying cause,
      associated heart disease, and history of previous embolism. Decisions regarding
      warfarin anticoagulation therapy require a careful assessment of relative risks
      of thromboembolism and bleeding. Anticoagulation is strongly indicated for
      valvular atrial fibrillation and to prevent recurrent stroke in patients with
      atrial fibrillation and previous stroke or transient ischemic attack. Several
      randomized trials have consistently shown a reduction of the risk with the use of
      warfarin in nonvalvular atrial fibrillation, and anticoagulation is recommended.
      With a careful selection of patients, the risk of major bleeding on warfarin
      therapy is 2% to 4% per year. Aspirin therapy is less efficacious but also less
      risky than warfarin. Patients younger than 60 with lone atrial fibrillation do
      not require anticoagulation.

PMID- 7571565
TI  - Botulinum toxin for hyperfunctional facial lines.

PMID- 7571566
TI  - Facial implants in head and neck surgery.

PMID- 7571567
TI  - Changing aspects of epiglottitis.

PMID- 7571568
TI  - Phonosurgery--outcomes of varied techniques.

PMID- 7571569
TI  - Endoscopic forehead lift.

PMID- 7571570
TI  - An unusual cause of dysphagia.

PMID- 7571571
TI  - Nontraumatic splenic hematoma related to cocaine abuse.

PMID- 7571572
TI  - Hantavirus infection following wilderness camping in Washington State and
      northeastern California.

PMID- 7571573
TI  - Screening for cancer. Is it worth it?
AB  - A delay in diagnosing cancer is widely perceived to compromise severely a
      patient's chance of being cured. The unrealistic expectations of technology and
      of physicians' capabilities are inconsistent with modern knowledge of the natural
      history of cancer. Established and recent precepts in clinical oncology and tumor
      biology emphasize that inherent characteristics of a malignant neoplasm predict
      its dissemination, rather than a real or perceived delay in diagnosis. The
      processes of carcinogenesis and dissemination are more nearly simultaneous than
      sequential. Uncritical belief in the ability of most cancer screening techniques
      to provide cure through early detection may do more harm than good. Policy and
      efforts would be better directed to the primary prevention or reversal of
      preneoplasia and to improved therapy for established cancer.

PMID- 7571575
TI  - On losing face.

PMID- 7571574
TI  - Screening for cancer. Useful despite its limitations.
AB  - Effective primary prevention strategies are currently available for only a
      limited number of types of malignant neoplasms. In the meantime, the most
      effective intervention for cancer control is screening for the early detection of
      cancer in otherwise asymptomatic persons. Screening is probably most useful for
      cancers wherein the stage at diagnosis is clearly related to curability. Early
      detection by screening has been shown to lead to a better outcome following the
      treatment of cancers of the breast, cervix, and colon. Screening for cancer also
      enables preneoplastic states to be detected and treated. Screening programs offer
      an opportunity to enhance the potential of chemoprevention. New cancer screening
      tests will soon be developed, including some that will detect known genetic
      predispositions to cancer. Each new screening test must be critically evaluated
      in rigorous studies before being embraced or rejected by clinicians and patients.
      In particular, screening efficacy must be demonstrated as judged by improved
      survival of those screened.

PMID- 7571576
TI  - Anatomy lessons.

PMID- 7571578
TI  - More on Mycoplasma pneumoniae pneumonia.

PMID- 7571577
TI  - Warfarin sodium or aspirin therapy to prevent stroke in nonrheumatic atrial
      fibrillation. Answered and unanswered questions.

PMID- 7571579
TI  - More on Mycoplasma pneumoniae pneumonia.

PMID- 7571580
TI  - Hereditary hemochromatosis--importance of age and sex?

PMID- 7571581
TI  - More on the prostate cancer screening controversy.

PMID- 7571582
TI  - Telephone use and costs in a group subspecialty practice.

PMID- 7571583
TI  - Dimensions of care of the dying patient.

PMID- 7571584
TI  - Frustrated mastery. The cultural context of death in America.
AB  - The care of dying patients as a problem in the United States cannot be well
      understood apart from understanding the way in which American culture has
      responded to the problem of death. This country seems unusual among developed
      countries in its passion to conquer death, often acting as if death were simply
      one more disease to be overcome. American medicine has been influenced by this
      background culture, while adding some idiosyncratic features of its own. A
      powerful attraction to technology, a fear of malpractice litigation, and a
      fundamental ambivalence about the response physicians should have to death help
      to explain why the care of dying patients has been so difficult, so
      controversial, and so troubling to both the medical and the lay communities.

PMID- 7571585
TI  - Religious dimensions of dying and death.

PMID- 7571586
TI  - Patients' perspectives on dying and on the care of dying patients.
AB  - Dying patients have much to teach us about their preferences for care. Although
      caring for dying patients is a major responsibility of physicians, the current
      curriculum in medical education emphasizes the pathophysiology and treatment of
      disease, with scarce time and emphasis for developing attitudes and skills
      essential to caring for persons in the final stage of life. Barriers to
      satisfactory communication may arise from either the physician or the patient, or
      both. Patients and physicians sometimes attach different meanings to words that
      are commonly used in discussing treatment. Barriers can be diminished or resolved
      by applying good communication skills, including attending to both verbal and
      nonverbal signals, exploring incongruent affect, and empathically eliciting
      patients' perspectives about illness, treatment plans, and end-of-life issues.
      The competent care of dying patients must extent beyond the management of
      physical symptoms because patients may experience their gravest suffering from
      fears and anxieties that go unaddressed in conversations with their physician.
      Conflicts arise when the disease progresses and the end of life approaches if the
      physician and patient have not reached agreement on their expectations.
      Physicians may initiate life-prolonging mechanisms when patients actually prefer
      palliative care. Patients experience a reduction in both physical and
      psychological aspects of suffering when physicians use good communication skills,
      are sensitive to patients' perspectives, and actively work to reduce barriers to
      mutual understanding.

PMID- 7571587
TI  - Understanding cultural difference in caring for dying patients.
AB  - Experiences of illness and death, as well as beliefs about the appropriate role
      of healers, are profoundly influenced by patients' cultural background. As the
      United States becomes increasingly diverse, cultural difference is a central
      feature of many clinical interactions. Knowledge about how patients experience
      and express pain, maintain hope in the face of a poor prognosis, and respond to
      grief and loss will aid health care professionals. Many patients' or families'
      beliefs about appropriate end-of-life care are easily accommodated in routine
      clinical practice. Desires about the care of the body after death, for example,
      generally do not threaten deeply held values of medical science. Because expected
      deaths are increasingly the result of explicit negotiation about limiting or
      discontinuing therapies, however, the likelihood of serious moral disputes and
      overt conflict increases. We suggest a way to assess cultural variation in end-of
      life care, arguing that culture is only meaningful when interpreted in the
      context of a patient's unique history, family constellation, and socioeconomic
      status. Efforts to use racial or ethnic background as simplistic, straightforward
      predictors of beliefs or behavior will lead to harmful stereotyping of patients
      and culturally insensitive care for the dying.

PMID- 7571588
TI  - Accurate prognostications of death. Opportunities and challenges for clinicians.
AB  - Linking survival time to an array of prognostic variables through a powerful
      statistical model can provide reliable, valid and potentially useful information
      for patient care. We present a summary of the recently developed SUPPORT model
      [Study to Understand Prognoses and Preferences for Outcomes and Risks of
      Treatment] for estimating survival time of seriously ill adult inpatients and
      illustrate the possible clinical use of such a model. This model is then
      translated into counseling. Clinicians are positioned to evaluate the relevance
      and validity of any model and to understand their persistent shortcomings.

PMID- 7571589
TI  - Improving care of dying children.
AB  - Every year about 5,000 children aged 0 to 14 years need hospice care in the
      United States. Children seem to know that they are dying, although this is
      difficult for parents to accept. Clear, empathic understanding is needed.
      Communication with clarity and understanding is imperative with the changes in
      goals from cure to palliation to comfort. The ideal place for most dying children
      is at home, where symptoms can be managed as effectively as in a hospital.

PMID- 7571590
TI  - How ethics consultation can help resolve dilemmas about dying patients.

PMID- 7571591
TI  - Clinical management of dying patients.
AB  - Dying is universal, and death should be a peaceful time. Myriad comfort measures
      are available in the last weeks before life ends. Discussions about end-of-life
      issues often suffer from lack of informed opinion. Palliative care experts have
      identified specific somatic and psychological sources of distress for dying
      patients and their loved ones. Pain, shortness of breath, nausea and vomiting,
      and fear of abandonment contribute substantially to both physical and
      psychological discomfort toward the end of life. Simple, effective methods exist
      for relieving those symptoms. Knowledge about the natural events associated with
      dying and an informed approach to medical and psychological interventions
      contribute to systematic and successful comfort care. We describe the origin of
      physical and psychological distress at the end of life and provide strategies for
      alleviating many of the discomforts.

PMID- 7571592
TI  - Suffering and dying in cancer patients. Research frontiers in controlling
      confusion, cachexia, and dyspnea.

PMID- 7571594
TI  - Care of the family when the patient is dying.
AB  - Families shoulder many burdens during terminal illness. Their needs grow and
      change as their loved one's illness progresses. We describe specific physician
      behaviors that can assist families in coping with terminal illness. Early in
      serious illness, there are the emotional burdens of learning of the illness and
      coming to accept a terminal diagnosis, of giving up hope of cure. As terminal
      illness progresses, patients often need family members to help refocus hope
      despite the inevitability of death. Patients and families need support, guidance,
      and encouragement to begin planning for many decisions. Although emotional
      burdens are felt by most family members, families who choose to have their loved
      one die at home take on enormous direct caregiving burdens as well. They need
      information and supplies, including specific teaching of caregiving skills and
      logistic support. After the death of the loved one, family members have
      bereavement needs that require ongoing support.

PMID- 7571593
TI  - Medical futility and care of dying patients.
AB  - In this article, I address ethical concerns related to forgoing futile medical
      treatment in terminally ill and dying patients. Any discussion of medical
      futility should emphasize that health professionals and health care institutions
      have ethical responsibilities regarding medical futility. Among the topics I
      address are communicating with patients and families, resolving possible
      conflicts, and developing professional standards. Finally, I explore why
      acknowledging the futility of life-prolonging medical interventions can be so
      difficult for patients, families, and health professionals.

PMID- 7571595
TI  - Defining and evaluating physician competence in end-of-life patient care. A
      matter of awareness and emphasis.

PMID- 7571597
TI  - Reproductive health and managed care. An overview.

PMID- 7571596
TI  - End-of-life treatment in managed care. The potential and the peril.

PMID- 7571598
TI  - Women's reproductive health services in health maintenance organizations.

PMID- 7571599
TI  - Quality assessment of reproductive health services.
AB  - Systematic information on the quality of health services is being sought by
      purchasers and providers of health care. Consensus on an appropriate set of
      quality assessment criteria should stimulate the development of data collection
      tools and analytic methods. To begin the dialogue, criteria for evaluating the
      quality of family planning services, routine gynecologic care, infertility care,
      male reproductive health services, prenatal care, and early postnatal care are
      necessary. The effect of report cards on measurement and reporting and the
      challenges of assessing quality in family planning and other clinic settings are
      discussed.

PMID- 7571601
TI  - Beyond the freedom to choose. Medicaid, managed care, and family planning.
AB  - In this article we examine the federal freedom-of-choice statute, which was
      enacted in the mid-1980s to protect Medicaid beneficiaries' access to timely and
      confidential family planning services. We also examine how these provisions have
      been implemented in 15 jurisdictions and provide a case study of 5 family
      planning programs. We found that this attempt to "carve out" family planning
      services from managed care has led to numerous problems. First, there is
      virtually no federal guidance concerning to which services and supplies the
      exemption applies. Second, there are no guidelines as to how carve-outs are to
      function. Therefore, if managed care systems are inaccessible or nonresponsive to
      reasonable community care seeking patterns, then a carve-out carve-out may be the
      only answer. Carve-outs should be used as a last resort, however, because they
      are so difficult to design.

PMID- 7571600
TI  - Standards of care in reproductive health services.
AB  - Standards of care for all medical services are designed by and for professionals
      and generally follow medical professional society guidelines. Most managed care
      organizations rely on professional medical standards of practice, which provide
      broad guidelines to providers. Family planning agencies, on the other hand,
      generally follow Title X program guidelines, which provide specific standards of
      care. The Title X guidelines include detailed instructions about service delivery
      and program content. The differences between these two sets of standards result
      in a wide variation in practice guidelines across the spectrum of health care
      providers. From the patient perspective, evaluation of care is generally not
      related to professional standards, but instead focuses on quality measures
      related to access and interpersonal aspects of care. The member satisfaction
      surveys developed by some managed care organizations now have a large enough
      sample size to provide meaningful measures of patient satisfaction at the
      individual provider level. A uniform set of practice guidelines is needed for
      family planning services that incorporates the strengths of all three approaches
      and that link performance to generally accepted practice guidelines.

PMID- 7571602
TI  - Case studies of collaboration between family planning agencies and managed care
      organizations.
AB  - To learn more about collaboration between family planning agencies and managed
      care plans, telephone interviews were conducted with staff at ten sites across
      the country, including offices of Planned Parenthood and other agencies. These
      examples of collaboration indicate that the development of each partnership is
      influenced by contextual factors such as the penetration of managed care into the
      local market, the patient profile of the clinics, government regulations, and the
      political environment. Although establishing relationships with family planning
      agencies is often not a high priority for the health plan organizations, they
      prefer to deal with networks of providers when the need for a family planning
      referral arises. Family planning agencies are increasingly moving toward
      expansion of services into primary care to make themselves more attractive to
      managed care plans. Developing strategies for sharing information while
      maintaining patient confidentiality represents an important challenge to family
      planning agencies as they move toward integration with managed care plans. Family
      planning providers also face obstacles because they are not usually organized to
      handle the complex financial and contractual issues that come with collaboration.

PMID- 7571603
TI  - Family planning, managed care, and rural America.
AB  - Within the United States, rural residents encounter a greater number of barriers
      in accessing health care services than their urban counterparts. In general,
      rural Americans have less access to both family planning services and managed
      care delivery systems. Given the rapid changes in health care, we reviewed the
      implications for the provision and integration of family planning and managed
      care services in rural areas, where there is limited experience in establishing
      working relationships between those services. In many instances, family planning
      services are well established in rural areas where managed care has not yet
      penetrated. Our case study in Minnesota suggests that, although managed care and
      family planning services are developing in rural areas, there is little evidence
      of collaboration. Several innovative and successful family planning projects do
      exist in rural areas, however, and serve as models of successful population-based
      programs that could work well with health plans. Although this study concentrated
      on the provision and utilization of subsidized family planning services, there is
      a compelling need for further work to determine accurately where rural residents
      are accessing such services and how the expansion of managed care will affect the
      delivery of reproductive health care.

PMID- 7571605
TI  - Reproductive health practices of HMOs serving urban low-income women.
AB  - As managed competition expands, many health plans wish to open their membership
      to those on Medicaid, mostly women and children. This study examines the
      reproductive services of 10 diverse managed care organizations historically
      targeting large numbers of poor women for care through prepaid Medicaid
      contracts. These institutions think themselves united and unique within managed
      care because of their long-term commitment to serving patients on Medicaid.
      Although the interviews with providers and administrators explore many aspects of
      reproductive care, most of these health maintenance organizations (HMOs), by the
      nature of their funding and federal mandates, have more aggressive and defined
      programs for pregnant women and for infants. These urban-based providers have
      discovered by trial and error the challenges of getting quality health care to
      poor women: external administrative or bureaucratic challenges because of
      Medicaid, internal administrative or provider barriers, and the artifacts of
      patient behavior. Strategies to address these problems involve attending to
      political and bureaucratic factors affecting care, taking a broader social view
      of patients and their community, using community resources to supplement HMO
      benefits, maximizing each contact with patients with multiple interventions, case
      management to monitor underutilization, aggressive outreach, service, and follow
      up.

PMID- 7571604
TI  - Promising approaches for adolescent reproductive health service delivery. The
      role of school-based health centers in a managed care environment.
AB  - Within the arena of adolescent health care, the most critical service delivery
      issue is access to care. Efforts to contain health care expenditures through
      managed care plans inevitably conflict with efforts to deliver truly
      comprehensive preventive services to all adolescents. Because of the substantial
      increase in risk behaviors, prevention efforts require frequent contacts if
      interventions are to be made before risk behaviors occur or soon after their
      onset. In addition, yearly screening for all adolescents is likely to identify
      many teens who could benefit from early interventions. Enabling school-based
      health centers to provide services in coordination with managed care systems
      would go far to ensure access to care, as well as appropriate attention to the
      special needs of adolescents, in a timely and cost-effective way. Furthermore,
      that access would not be tied solely to the family's choice of provider or to the
      provider mandated by the adolescent's insurance plan. Underlying any approach to
      coordination of services, however, is the need for managed care providers to
      understand and affirm a preventive care investment in young people as a means of
      reducing health care expenditures, an investment that would pay dividends not
      only during the adolescent years but into adulthood as well. Whether the
      willingness exists to make this investment, when the cost savings may not
      directly accrue to the adolescent's current HMO, presents a conflict between the
      present interests of the HMO and the future interests of whatever provider the
      adolescent sees as an adult. As managed care systems are more widely adopted, it
      will be important to ensure that they adequately incorporate the service delivery
      components that have been found to be efficacious in serving adolescents. Given
      the leading role school-based health centers can play in providing preventive
      health care and health promotion, managed care providers should be encouraged to
      develop strong partnerships with such centers, so that the dual goals of high
      quality care and cost containment can be achieved.

PMID- 7571606
TI  - Health plan marketing and reproductive health services.

PMID- 7571608
TI  - Women's reproductive health. A Catholic perspective.

PMID- 7571609
TI  - Women's health care in an IPA setting.

PMID- 7571610
TI  - Integrating essential public health services and managed care. Family planning
      and reproductive health as a case study.

PMID- 7571607
TI  - Reproductive health care delivery. Patterns in a changing market.
AB  - Providers of reproductive health services, including clinics and office-based
      physicians, face new challenges as the American health system progresses toward
      managed care. Although services for low-income women are often subsidized, the
      average out-of-pocket payments for reproductive health services are the same for
      women with incomes below and above 200% of the poverty level. Although many
      women, especially those classified as low income, use clinics, most say that they
      would prefer to receive care in a private physician's office and in a place where
      they can get general health care as well. Multivariate analyses indicate the
      importance of type of insurance and source of primary health care in affecting a
      woman's selection of her reproductive health care provider. Specialized providers
      such as family planning clinics need to consider how they can blend with managed
      care plans.

PMID- 7571612
TI  - [The significance of measuring blood flow in the common carotid artery by the
      Doppler method for detection of orthostatic disturbances of the cardiovascular
      system in children].
AB  - In 35 children of either sex, aged 11-15 years with orthostatic disturbances and
      in 35 children of the same age without these disturbances, the maximal blood flow
      rate was assessed in the common carotid artery using Doppler technique during 10
      minute passive orthostatic test on a tilting table. During passive tilting to
      upright position, the mean values of the maximal blood flow rate in the children
      with orthostatic disturbances were lower than those in the healthy children. The
      measurement of the maximal blood flow rate in the common carotid artery by the
      Doppler method may be a useful clinical method of detection of functional
      cardiovascular disturbances connected with body position in children.

PMID- 7571611
TI  - [Clinical effect of nitrates (Olicard 40) and their influence on deforming of
      erythrocytes against the background of 24-hour catecholaminuria].
AB  - Progress in the investigations upon factors influencing the course of the
      ischemic heart disease focused our attention on the deformability of
      erythrocytes. That attribute of the red blood cells (RBC) is described by their
      susceptibility to changes in shape without changing volume. Because of that
      feature, RBC can reach the smallest capillaries of the circulatory system. The
      aim of the study was to determine the influence of mononitrates (Olicard Ret.) on
      the deformability of RBC (EDI) in correlation to the clinical course of the
      ischemic heart disease and to evaluate the role of catecholamines in the course
      of the disease and their influence upon EDI. 30 patients (pts) treated with
      mononitrates for 4 weeks were enrolled into the study. In 27 pts clinical
      improvement was recorded, as evaluated by the results of repeated exercise tests
      and changes in the number of anginal attacks. Mean weekly number of anginal
      attacks decreased from 6.2 to 2.1 (p < 0.05), and parameters of exercise tests
      improved: DP/Wmac decreased from 0.694 to 0.479 (p < 0.001) and maximal workload
      attained increased from 6.8 to 9.0 METS (p < 0.001). Correspondingly to the
      clinical improvement, beneficial changes in RBC deformability were seen: 0.033 vs
      0.040 (p < 0.01). Correlation factor for changes in EDI (r = 0.628) was higher
      than that for the number of anginal attacks (r = 0.589), but lower than the
      correlation factor for exercise test parameters (r = 0.969 for DP/Wmax and r =
      0.858 for METS). There were no significant changes in the urinary output of
      catecholamines and no correlations were seen between urinary output of
      adrenaline, noradrenaline and EDI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571613
TI  - [Concentration of serum sulphydryl groups in patients with rheumatoid arthritis
      dependent on age and duration of disease].
AB  - In 67 patients with classical or certain (according to the ARA criteria)
      rheumatoid arthritis, the concentration of serum sulphydryl groups (SH) was
      studied. A statistically significantly decreased concentration of these groups
      was found in the patients with rheumatoid arthritis (397.1 +/- 31.7 mumol/l).
      Besides that the studies demonstrated that the concentration of serum SH groups
      depended on the age of the patients and duration of the disease. For example, in
      time range of disease duration from one to 15 years, the concentration of SH
      groups was 395.9 +/- 28.5 mumol/l, from 16 to 20 years: 337.0 +/- 32.0 mumol/l,
      and from 26 to 30 years: 290.0 +/- 17.2 mumol/l. The changes of the concentration
      of serum SH groups in patients with rheumatoid arthritis may become, according to
      many researchers, a very sensitive biochemical index in the assessment of the
      course of the inflammatory process.

PMID- 7571615
TI  - [Use of ultrasonography for the diagnosis of breast tumors].
AB  - In the paper, the use of USG is presented in the diagnosis of breast tumours. On
      the basis of own material from the Breast Disease Diagnosis Unit, the authors
      presented the usefulness of USG examination in detection of breast diseases as
      easily available, non-invasive and not cumbersome for the patient.

PMID- 7571614
TI  - [Assessment of iron absorption in children with chronic renal insufficiency].
AB  - The changes were compared of the iron curve in children with chronic renal
      failure and with terminal renal failure after oral loading dose of ferrous
      sulphate. Flat curve of absorption was found in both groups of patients with
      increased stores of systemic iron and high values of transferrin saturation index
      (TSI). Steep iron curve and very good absorption were found in all children with
      decreased serum level of ferritin and decreased TSI. The curves of iron
      absorption at serum ferritin level 250-500 ng/ml pointed to impaired absorption
      and depended on the initial TSI value and initial iron level in the serum. No
      significant differences were found in the shape of iron curve depending on
      dialysing methods. Studying of the iron curve and values of TSI in certain
      patients makes easier the decision of administration of treatment with oral iron
      preparations even with increased values of TSI and ferritin in the serum.

PMID- 7571616
TI  - [Laparoscopic image of sexual organs in women after ovulation induction].
AB  - The assessment was performed of laparoscopic images of the sex organ in 58 women
      after induction of ovulation. Abnormalities were found in 29 women with permanent
      lack of ovulation and in six women with achieved ovulation. The changes in the
      oviducts predominated with an astonishingly low per cent of incidence of
      endometriosis (5) which probably was not a clinical problem in non-effective
      ovulation induction. The decision of laparoscopy should be considered also in the
      cases in which HSG performed earlier gave positive results.

PMID- 7571618
TI  - [Surgical treatment of neoplasms in the body of the uterus--clinical analysis of
      115 cases].

PMID- 7571619
TI  - [Demographic characteristics of mothers giving birth to live children with
      myelomeningocele].

PMID- 7571617
TI  - [A simple method for management and treatment results of pregnant women with
      isthmo-cervical insufficiency].
AB  - A simple way of management of patients treated for isthmo-cervical insufficiency
      in the Department of Obstetrics and Gynaecology, Medical Academy in Bydgoszcz in
      the years 1980-1990 was subjected to own assessment. During this period the
      treatment was given to 684 pregnant patients with diagnosed isthmo-cervical
      insufficiency, laying a circumferential suture onto the cervix after Hervet,
      between 17 and 33 weeks of pregnancy. The accepted management after the procedure
      was limited to bed rest and administration of analgesic and spasmolytic drugs.
      Positive results of the established treatment were found in 95.4% of the patients
      with diagnosed isthmo-cervical insufficiency which made possible its routine
      introduction.

PMID- 7571622
TI  - [Perspectives on prevention and treatment of diabetes mellitus type I (IDDM)].

PMID- 7571620
TI  - [Geography of mortality from all malignant neoplasms (Nr 140-208 according to the
      international classification of diseases) in the Katowice province in the years
      1985-1990].
AB  - In the Province of Katowice, taking into account 93 administration units (45
      towns and 48 communes), the geography of mortality from all malignant neoplasms
      of men and women in the years 1985-1990 was established. Some regions of the
      Province are at particular risk: form men they are mainly regions with mortality
      index exceeding 240 cases per 100,000 (Fig. 1), and for women regions with
      mortality index exceeding 130 cases per 100,000 (Fig. 2). In comparison to the
      available statistics of mortality from malignancies from other countries (and in
      them especially from industrialized regions similar to Upper Silesia) the level
      of the risk for malignancy development in the population is, as a rule, higher in
      Upper Silesia. The cohort analysis demonstrates in turn further progression of
      mortality from malignancies in the Upper Silesian populations in the next years.

PMID- 7571621
TI  - [Allergic bronchitis in bronchial asthma].
AB  - Asthma was known already in ancient times. International Consensus Report on
      Diagnosis and Management of Asthma published in 1993 gives its updated
      definition, classification and treatment, but pathomechanism and
      pathophysiological differences between atopic and non-atopic asthma remain
      unclear. Most commonly accepted is the inflammatory conception of asthma
      presented by Kay in 1983. Eosinophil, lymphocyte and their products seem to play
      an important role in allergic inflammation. A raise of interest toward adhesion
      molecules role has been observed lately.

PMID- 7571623
TI  - [Fear as a risk factor in perinatology].
AB  - The fear as a risk factor in perinatology--the review of the recent literature.
      Fear is the main symptom of the psychological stress. It is the main component of
      almost all pathological syndromes. Fear stimulates sympathetic nervous system
      switching the metabolism to the catabolic pathways. It has fetal influence on the
      course of pregnancy, fetal development and pregnancy loss rate. Stress
      situations, overwork, bad social conditions, bad obstetrical history, pregnancy
      complications and unsatisfactory care are responsible for the appearance of fear
      during pregnancy. Perinatal psychoprophylaxis is the main factor in suppressing
      fear in pregnant women.

PMID- 7571624
TI  - [Toxoplasmosis as a risk factor in pregnant women after renal transplantation].
AB  - Toxoplasmosis is an anthropo-zoonosis caused by the protozoa Toxoplasma gondii.
      The frequency of infection in the population of adults is estimated at 30-50%.
      Acquired toxoplasmosis takes a differentiated clinical course. It is usually
      symptomless or the symptoms are indistinct. In case of immunosuppressive
      treatment of the host severe Toxoplasma gondii infections can occur. There also
      is a possibility of transmission of the protozoa via transplant from the donor to
      the recipient as well as the possibility of reinfection of the acquired
      infection. In perinatal medicine toxoplasmosis plays a particularly important
      part due to the possibility of the transmission from mother to foetus. It seems
      therefore that women who are chronically treated with immunosuppressive eg after
      a renal transplant deserve special medical attention.

PMID- 7571625
TI  - [Congenital fructose intolerance diagnosed in a 13-year-old boy].
AB  - We describe the case of 13 year old boy who was admitted to the hospital in order
      to find the reason of hepatomegaly and increased echogenicity observed in
      sonography. The thorough anamnesis revealed aversion to products containing
      fructose and thus hereditary fructose intolerance appeared the most probable in
      this case. The preliminary diagnosis was confirmed by oral fructose tolerance
      test.

PMID- 7571627
TI  - [Stab wound of the right atrium of the heart].
AB  - A case is presented of heart wound treated surgically as emergency with positive
      result. The attention is paid to the necessity of introduction of therapeutic
      management in the hospital to which the patient was admitted.

PMID- 7571626
TI  - [Intrarenal cyst communicating with the kidney calyx, suggesting tuberculous
      changes].
AB  - The authors presented a female patient in whom intrarenal cyst was found
      communicating with the calyx-pelvic system, suggesting a tuberculous lesion. The
      attention was paid to the possibility of diagnostic error. The probable
      pathogenetic mechanism of intrarenal cyst development is described.

PMID- 7571628
TI  - [Ludwik Perzyna--an outstanding author and promotor of medicine, the first author
      of Polish medical terminology].

PMID- 7571629
TI  - [HIV infections and their prophylaxis in the homosexual community of the Gdansk
      province].
AB  - From 1985 to the end of 1993, 15,000 investigations were performed in total, for
      HIV infection in the Province of Gdansk. Positive results of the tests were found
      in 316 persons, over 60% of whom being intravenous drug-addicts. In the group of
      persons reporting the possibility of infection through sexual contacts, the
      infection was found only in 15 out of 1755 studied subjects. Among homosexuals
      the infection was found in four out of 167 persons who underwent the
      investigation. In the whole group of 316 infected subjects this accounted for
      1.2%. The above mentioned numbers are certainly too low. The causes of this
      should be seen in generally low attendance rate to the tests connected with low
      social awareness. However, in persons with different sexual orientation this is
      caused also by the fear of manifestation of their pecularity. In the activities
      for the control of HIV epidemic spreading in Poland indispensable is multi-sided
      educational initiative including the whole population, in which great help may be
      provided by homosexuals themselves. An evidence of this may be the results as yet
      of the cooperation between representatives of health care and homosexuals,
      discussed in the present paper.

PMID- 7571630
TI  - [Viruses of parasitic protozoa].
AB  - The authors present the actual review on several publications concerning the
      molecular characterizations of the viruses found in parasitic protozoa such as
      Giardia, Trichomonas, Leishmania and Entamoeba histolytica. All of the RNA
      viruses observed in parasitic protozoa showed several similarities and did not
      considerably differ from the viruses found in simple eukaryotic cells; they
      closely correspond to dsRNA viruses of yeast. The supposition that the protozoan
      symbionts detected in laboratories transfer to their hosts in natural conditions
      seemed to be rational, though, there are no evidences that these symbionts are
      potential pathogens. However, the opinion reiterates that intestinal protozoa
      (e.g. Entamoeba histolytica) may serve as vectors for HIV or cofactors of HIV
      infection. The authors point out that irrespective of the potential role of
      viruses as vectors in the transfection system for parasitic protozoa, the
      observed viral system constitutes an unusual experimental system to solve the
      problems of gene expression.

PMID- 7571631
TI  - [Occurrence of parasites, bacteria, viruses and fungi in fish that are pathogenic
      to men and fish].
AB  - Parasitological examinations comprised above 20,000 fish which were searched for
      parasitic nematoda of Anisakidae. It was evidenced that herring were infected
      with anisakid larvae in 8%, cod and flatfish in 4% and the eelpouts in as many as
      in 52%. The species that prevails in these fish were: Anisakis simplex,
      Contracaecum osculatum C, Hysterothylacium auctum and Pseudoterranova decipiens,
      respectively. In direction of the bacteria pathogenic to man 765 fish were
      examined; in 38% there were found pathogenic strains such as coagulase-positive
      staphylococci, even Salmonella and Shigella. Besides there were cultivated 109
      strains of bacteria pathogenic to fish belonging to the genera: Aeromonas,
      Pseudomonas, Acinetobacter and Moraxella Virological evaluation comprised 527
      fish, in that number Enteroviruses (Coxsackie, ECHO) were identified in 31% fish
      and viral agent, likely to be pathogenic to fish in 8% specimens. Not a one case
      of infection with Ichthyophonus hoferi fungus in the herring hitherto examined
      was noted.

PMID- 7571632
TI  - [Cryptosporidiosis--a typical environmental parasitosis].
AB  - The article reviews the problems on epidemiology of cryptosporidiosis and gives a
      detailed description of the massive waterborne outbreak in Milwaukee (Wisconsin,
      USA) associated with a break in filtration capacity of a public water supply. The
      authors emphasize the need for high-quality diagnostic procedures as current
      coprodiagnostic microscopical techniques seemed to fail to detect Cryptosporidium
      oocysts.

PMID- 7571633
TI  - [Histological and histochemical investigations of large and small intestine in
      guinea pigs infected by entamoeba histolytica].
AB  - In order to gain better knowledge about pathomechanisms of amebiasis,
      histological and histochemical studies were performed on large and small
      intestine of guinea pigs infected by PS-2 Entamoeba histolytica strain. Results
      of these studies showed that the presence of E. histolytica in large intestine
      caused also pathomorphological changes of small intestine: partial atrophy of
      villi, epithelium destruction, epithelial metaplasia, lacteral dilation,
      infiltration of mucous membrane by lymphocytes, plasmocytes and macrophages.
      Influence of this parasite on lowering of investigated enzyme reactions and
      reduction of mucus secretion in large intestine as well as in small intestine of
      infected animals were also shown. These results suggest influence of E.
      histolytica cytotoxins (studied earlier by others authors) on the enzymes
      activity in host tissues and next on the weakness of intracellular metabolism and
      on cells destruction. For induction of these changes the adhesion host cell
      amoeba is not necessary.

PMID- 7571634
TI  - Changes in the diameter of Isospora lacazei (Labbe, 1893) oocysts in the house
      sparrow, Passer domesticus (L.).
AB  - Differences in the diameter of Isospora lacazei oocysts were found to be
      dependent on diet and other factors. House sparrows which were given animal
      products as food (hard boiled eggs) excreted with their faeces coccidia oocysts,
      which were larger than when they were fed grain. The results indicate a need to
      verify the divisions of the systematics of Isospora lacazei.

PMID- 7571636
TI  - [Anguilluliasis of the European eel--a continuing problem].

PMID- 7571635
TI  - [Strongyloidosis. Part II. Pathogenesis and pathology].
AB  - Pathogenesis and pathology of alimentary system of man infected with
      Strongyloides stercoralis are shown. Allergic, macroscopic lesions of duodenal,
      small and large intestinal walls, existing in different clinical strongyloidosis
      types are discussed. The role of endo-autoinfection in the course of
      strongyloidosis in the immunocompromised patients with fatal disseminated
      strongyloidosis is shown. In disseminated strongyloidosis lesions include
      stomach, liver and rarely pancreas. Pathogenesis of macroscopic and microscopic
      lesions in respiratory, circulatory and central nervous systems of a man infected
      with Strongyloides stercoralis, mainly in the course of fatal disseminated
      strongyloidosis, is shown. Rare cases of presence of parasite filariform larvae
      in urinary tract, reproductive system, and other organs are also given.

PMID- 7571637
TI  - [The question of pathogenesis of parasitic castration in snails infected with
      developmental stages of digenetic trematodes].
AB  - In the article several models of pathogenesis of parasitic castration of snails
      infected with developmental stages of digenetic trematodes are presented. Some
      aspects of mechanical and chemical damage of the gonad and changes in tissues of
      this organ, caused by its starvation--developing as a consequence of competition
      between the host and its parasites, are discussed. Particular attention was paid
      to potential effect of the parasitic larvae on physiology of the hormonal system
      of the host.

PMID- 7571639
TI  - [Activity of alpha-amylase, trypsin and lipase in pancreas and duodenal contents
      of Ascaridia galli infected chickens fed with various proteins].
AB  - The study was carried out on Astra S chickens which were grown on diets
      containing 11% and 19% proteins. In homogenized pancreas and duodenal contents
      from control animals and chickens infected with 500 invasive eggs of Ascaridia
      galli activities of alpha-amylase (Fennel method), lipase (Cherry-Crandall
      method) and trypsin (Anson method) were determined. After 7 weeks of the invasion
      the activities of these enzymes were higher in duodenal contents and lower in
      pancreas of infected birds in comparison with the control animals. The
      differences were significant for alpha-amylase and lipase activities in animals
      which were given 11% protein diet, and for trypsin activity of chickens groups
      fed with 19% protein diet.

PMID- 7571640
TI  - [Fleas from the nests of goosander (Mergus merganser L.)].
AB  - In 1993 43 nests of Goosander from the Jasien Lake near Bytow were collected and
      checked on fleas presence. Ceratophyllus gallinae, the only one fleas species,
      was found in 60.5% nests. Among nests where the fleas were found the most
      frequent were those inhibited by 1-10 specimens of fleas (12 nests). The highest
      mean number of fleas per nest and the highest percentage of nests with fleas were
      noted before the breeding season has started (in March) and the lowest after the
      fresh brood in May. More fleas were noted in nests with successful broods. M.
      merganser was not yet noted in Polish literature as a host of C. gallinae in
      Poland.

PMID- 7571638
TI  - [Comparison of the variability of tapeworms obtained as a result of infecting
      rats with Hymenolepis diminuta larvae of different ages].
AB  - In Hymenolepis diminuta WMS "strain" tapeworms which were obtained 2.5 months
      after the administration to rats of 2-month old larvae--cysticercoids++, isolated
      from Tribolium destructor, only one-sided position of genital pores (PGP)
      developed. The extended 7-month duration of the invasion of H. diminuta larvae
      stimulates the development of variable PGP already in 14.1% of 2.5-month
      tapeworms. In tapeworms with exclusively one-sided PGP in the first of the two
      groups mentioned, the number of type 1p2a proglottids (1 testis on the poral side
      and 2 testes on the aporal side) as well as type 0p3a, 1p3a and 2p1a amounted to
      88.2%, 5.5%, 4.2% and 0.5%, respectively and similarly in the second group-
      88.3%, 5.6%, 4.5% and 0.6%, respectively. In tapeworms with variable PGP the mean
      number of the types of proglottids mentioned was different from (86.0%, 4.1%,
      3.8% and 4.1%, respectively) the same figure in tapeworms with one-sided PGP.
      Particularly high correlation was found to occur between the number of PGP
      variations and type 2p1a proglottids (r = +0.928, P < 0.01).

PMID- 7571641
TI  - [Strategies in management of heart transplantation candidates with tachycardic
      ventricular arrhythmia anamnesis].
AB  - We followed up 73 consecutive patients with a history of syncopal ventricular
      tachyarrhythmias on the waiting list for a heart transplant between 1st March
      1992 and 15th September 1994 with the aim of evaluating the impact of implantable
      cardioverter defibrillator (ICD) on survival. On registration 60 patients were
      considered fit enough to be ambulant whilst awaiting transplantation. 30 were
      given ICD therapy (group 1) and 30 were not (group 2). 13 patients required
      inpatient supervision for ventricular arrhythmias whilst awaiting
      transplantation, but received no ICD therapy (group 3). The 13 in-patients were
      in a worse clinical state (NYHA) than the 30 out-patients not given ICD (p <
      0.05). With respect to all other clinical and hemodynamic characteristics all
      groups were comparable. Waiting time for transplantation was also comparable in
      all groups (n.s., log-rank method). ICD therapy resulted in a significant
      improvement of survival in these high-risk patients prior to transplantation.
      Only 1 out of the 30 ICD patients (group 2) and 5 out of the 13 in-patients
      (group 3) (p < 0.05 log-rank method). During the waiting time group 3 patients
      were hospitalised longest (p < 0.05), but there was a clear trend that also ICD
      patients had to be hospitalised to an increased extent (n.s.). Cox multivariate
      regression analysis of this study population showed that the cardiac index (p =
      0.001) and lack of ICD therapy (p = 0.035) were the only independent significant
      predictors of mortality on the waiting list. ICD therapy had no influence on
      mortality after transplantation (n.s. log-rank method).

PMID- 7571642
TI  - [Efficacy of the implantable cardioverter-defibrillator in patients on the
      waiting list for heart transplantation].
AB  - 8 of 122 patients receiving an implantable cardioverter defibrillator (ICD) in
      our department since 1985 for the treatment of ventricular tachyarrhythmias were
      considered candidates for cardiac transplantation. In 6 of 8 patients, at least
      one successful ICD discharge (range 1-378 discharges) was documented in the
      follow up time until transplantation. These therapies included
      cardioversions/defibrillations as well as overdrive stimulation in sustained
      monomorphic ventricular tachycardia. 1 patient died shortly before receiving a
      compatible organ. The remaining 7 patients survived successful heart
      transplantation undertaken 7-34 months after implantation of the cardioverter
      defibrillator. Cardiac transplantation was not complicated in any of these
      patients by the previous ICD management. Our results show the high efficacy of
      ICD as "bridge to transplant" therapy unit cardiac transplantation.

PMID- 7571643
TI  - [The value of tilt-table examination in diagnosis of syncope: studies of 24
      patients].
AB  - Sudden hypotension, alone or combined with bradycardia is a major cause of
      syncope. 24 consecutive patients with a history of > 1 syncope of unknown
      aetiology were exposed to vagal provocation by the head-up tilt test. The
      clinical symptoms were reproduced in 11 patients under the given protocol,
      representing a sensitivity of 46%. The patients were followed up for 13.2 +/- 5.3
      months. 7 of the 11 patients (64%) with a positive result on tilting versus 2 of
      the 13 patients (15%) with a negative result had a relapse of syncope. There was
      no statistical difference between the groups with regard to the number of
      syncopal episodes before patients were included in the study. Syncope in the head
      up tilt test is, thus, a pointer towards identifying with a higher incidence of
      syncope on follow-up.

PMID- 7571645
TI  - [External quality assurance: a significant--and 25-year-old--element of quality
      management in the medical diagnostic laboratory].
AB  - An external quality assurance system in the medical diagnostic laboratory, which
      is an essential part of the modern total quality management (TQM) concept in the
      public health system, was established in Austria already 25 years ago. The
      development and the scope of this quality assessment system by the "Austrian
      Society for Quality Assurance and Standardization of Analyses in the Clinical
      Laboratory" (OQUASTA) are presented. The decreasing coefficients of variation of
      several parameters of the external quality assessment exercises demonstrate an
      increasing analytical precision and might be interpreted as an effect of this
      quality assurance system.

PMID- 7571644
TI  - [Blood pressure awareness in Austria: indicators of an increasing information
      deficit].
AB  - Attitudes and knowledge of the Austrian population concerning hypertension have
      been investigated on a regular basis for 15 years (1978-1993). In 1978 a public
      campaign of information on hypertension was conducted all over Austria. Between
      1978 and 1993 four representative population surveys, based on random samples,
      were performed (1978, 1984, 1990, 1993). The four surveys showed that maximal
      blood pressure awareness after the campaign was followed by a decrease of
      awareness between 1984 and 1993. Above all, lack of knowledge of personal blood
      pressure increased markedly over the observation period. The determinant "don't
      know my blood pressure" was self reported by 10% in 1978, 7% in 1984, rising to
      17% and 18% in 1990 and 1993, respectively. This increase was significant in
      females and males younger than 50 years. Nearly no differences were found in self
      reported high blood pressure and antihypertensive drug intake between 1978 and
      1993 (1978, 1984, 1990: 14%, 1993: 12% with respect to the former; 1978: 10%,
      1990: 11%, 1993: 8% with respect to the latter). In 1993 significantly less
      people than in 1978 reported that their blood pressure had been measured within
      the past three months (1978: 49%; 1993: 34%). People estimated overweight,
      alcohol, mental stress, and cigarette smoking as the most important risk factors
      for hypertension (89%, 89%, 88%, 83%, respectively). The importance of these risk
      factors in the eyes of the questioned population increased between 1978 and 1993,
      significantly in the case of cigarette smoking. Primarily a lack of information
      was found in knowledge of personal values, whereas knowledge of risk factors for
      hypertension was considerably higher. The results of the four surveys lead to the
      conclusion that the population should be informed about the health hazards of
      high blood pressure more intensively and people should be motivated to take an
      interest in their blood pressure.

PMID- 7571646
TI  - [Current status and future developments in noninvasive treatment of urinary
      calculi with extracorporeal shockwave lithotripsy (ESWL)].
AB  - Being a highly effective and minimally invasive treatment modality,
      extracorporeal shock wave lithotriopsy (ESWL) has come to be the therapy of
      choice in more than 80% of urinary stones. Apart from pregnancy and untreated
      coagulopathy as contraindications, generally accepted limiting factors are a
      stone size of > 2.5 cm and the presence of anatomical draining barriers. In such
      cases endourological procedures are indicated from the outset. Modern urinary
      stone therapy requires both extracorporeal and intracorporeal procedures of
      lithotripsy as indispensable complementary techniques. Third-generation
      lithotriptors are characterized by a dual stone location system (ultrasound and X
      ray) and painless treatment without any need for analgesia. The current rapid
      development of lithotriptors is mainly driven by economic aspects and market
      requirements like multipurpose or mobile applicability. The "ideal" lithotriptor
      enabling even more effective, safer, and more comfortable treatment has yet to be
      developed.

PMID- 7571647
TI  - [Urolithiasis in children].
AB  - Urolithiasis is rare in childhood (about 1%) and commonly associated with urinary
      tract infection. Like in adults ESWL is the minimally invasive treatment and
      therefore primary therapeutic approach. However, the passage of stone debris is
      less complicated than in adults and auxiliary measures are seldom needed. There
      is no evidence of soft tissue damage after ESWL, but in aspect of the growing
      organ lithotriptors with small focal zone and ultrasound location system are
      preferable. Obstructive anatomical abnormalities, if so, must be treated
      simultaneously. For prevention a strict antibiotic (longterm) therapy, according
      repeat antibiograms, and exclusion of metabolic disease are essential. Medication
      as well as special diets must be handled carefully or avoided as they might
      induce growth disorders.

PMID- 7571648
TI  - [Current status of percutaneous calculus therapy].
AB  - Ultrasonically-guided percutaneous nephrolithotomy (PNL) has largely replaced
      conventional open surgery for treatment of stones of the upper urinary tract. PNL
      has proved to be a safe and effective therapy of upper urinary tract calculi. The
      different therapeutic strategies using percutaneous nephrolithotomy, comprise PNL
      monotherapy (large renal pelvis stones, partial staghorn stones, stones in
      caliceal diverticula, stones and UPJ stenosis) and combination therapy with ESWL
      (complete staghorn stones). Results reveal high success rates with an acceptable
      risk of complications and morbidity.

PMID- 7571650
TI  - [Laser lithotripsy of the upper urinary tract].
AB  - Approximately 10% of all stone patients require an endoscopic stone treatment.
      With the advent of laserlithotripters a new technology became available,
      featuring extremely thin (200 microns) and flexible lithotripsy probes. As a
      consequence, miniscopes have been developed for endoscopic stone manipulation in
      the ureter. These miniscopes greatly facilitate ureteroscopy and expectantly will
      reduce complications associated with this procedure. The success rates of
      laserlithotripsy are in the 90% range, the only serious drawback are the high
      purchase costs of the laser. Independent from these new possibilities for
      intracorporeal lithotripsy, extracorporeal shockwave lithotripsy (ESWL) remains
      the first therapy of choice for ureteral calculi.

PMID- 7571649
TI  - [Flexible ureterorenoscopy: a method for minimally invasive diagnosis and therapy
      in the upper urinary tract].
AB  - Retrograde intrarenal surgery (RIRS) utilizing flexible, actively deflectable
      instruments has become a valuable asset in the diagnosis of upper urinary tract
      pathology and treatment of stone disease. Flexible endoscopic surgery of the
      proximal ureter and in the intrarenal collecting system constitutes the natural
      extension of rigid instrumentation in the upper urinary tract. At the UCLA Stone
      Center, retrograde ureteral and intrarenal surgery has become an integral part of
      our diagnostic and therapeutic armamentarium. This is documented by over 500
      treatments and diagnostic procedures performed in the upper urinary tract during
      the past 5 years.

PMID- 7571651
TI  - [The small urinary calculus: natural course and current treatment concepts].
AB  - Depending on size, duration of symptoms and their location in the collecting
      system urinary calculi may pass spontaneously in 16 to 93% of cases. The rate of
      infection and increase in size of stones in the renal pelvis or calix reaches 70%
      within months to years. Ureteral stones, however may lead to complications during
      a period of days to weeks. New minimally invasive treatment modalities have
      liberalized the indications for early intervention in cases of small stones.

PMID- 7571652
TI  - [The dilemma of metaphylaxis of urinary calculi].
AB  - Drug therapy in terms of prophylaxis of recurrent urolithiasis is known to be
      successful in inborn metabolic disturbances as cystinuria, primary hyperoxaluria,
      inborn errors of purine metabolism and calculi due to urinary infection. At the
      time efficient regimes for the large group of idiopathic urolithiasis are not
      available. The reason is that pathophysiology of urinary stone formation is still
      not fully understood. As a consequence of changing therapy in terms of
      extracorporal shockwave therapy and endourological lithotripsy, intensity of
      basic research in this field has markedly decreased. Optimizing prophylactic
      therapy of urolithiasis could only be achieved by development of completely new
      strategies from basic research.

PMID- 7571653
TI  - [Clinical manifestations of Parkinson disease].
AB  - The deficiency of dopamine leads to the lack of every-day movements and mobility.
      Loss of coordination and facial expression shows the complexity of non-verbal
      expression. This means a severe problem in communication. Especially the akinetic
      patient needs a lot of help from his/her surrounding. The clinically different
      forms of the disease will be shown due to the communicational and interactive
      aspects.

PMID- 7571654
TI  - [Stage-adjusted treatment of idiopathic Parkinson syndrome].
AB  - The treatment of idiopathic Parkinson's disease has been divided in 3 different
      phases. In the first phase the patient's disability is still minimal and a
      treatment with selegiline (possibly combined with an anticholinergic drug) is
      sufficient. In the second phase the treatment with levodopa (plus an
      decarboxylase inhibitor) becomes indispensable. In order to minimize the problems
      of long-term therapy a dopaminergic agonist (mostly bromocriptine) is added. The
      third phase is characterized by these problems. Some measures are discussed which
      may help to increase the patients' quality of life.

PMID- 7571655
TI  - [Future aspects of modern Parkinson therapy].
AB  - The present limitations of modern antiparkinsonian therapy (decreasing efficacy
      and increase of side-effects with advancing age and disease duration, lack of
      causal and neuroprotective therapies) require a multidisciplinary approach in
      basic, preclinical and clinical research. New substances with higher therapeutic
      potency and less side-effects, progress in functional stereotaxy, rehabilitation
      and restorative neurology, and new concepts in neurotransplantation as well as
      improved knowledge of etiology and pathophysiology are needed for an improvement
      of therapy.

PMID- 7571656
TI  - [Parkinson disease and neurologic rehabilitation].
AB  - Modern rehabilitation is becoming more and more "social integration" instead of
      "going back to work". Therefore rehabilitation is also a matter in chronic
      disease and in old people. Parkinson patients are somewhat disabled in nearly
      every aspect of their life, although the extent is related to the stage of the
      disease. Moreover, symptoms do not respond equally to drug treatment, balance
      (with succeeding falls) and swallowing being special problems for anti
      parkinsonian drug treatment, but also vegetative symptoms, dysarthria, motor
      skills etc. Apart from medication patients get relief also from adjuvant therapy
      like physiotherapy, occupational therapy, and speech therapy, which all can lead
      to improvement of quality of life. Rehabilitation needs team effort. Patient and
      family supporting groups (like Parkinson Disease Society and others) are an
      important factor for all needs of neurological rehabilitation.

PMID- 7571657
TI  - [Neurosurgical methods in Parkinson disease].
AB  - Advances in modern drug therapy of Parkinson's disease (PD) have displaced the
      surgical treatment of illness to second place. Beyond question, the modern
      medicinal treatment is the therapy of first choice for PD. However, at the same
      time it should not be forgotten that the stereotactic methods have a high
      therapeutic potential and should always be used for treating PD whenever
      medicinal therapy is unsuccessful or is not tolerated. For tremor this is
      sometimes the case. Neurostimulation, currently the most important neurosurgical
      treatment, involves a reversible, nonlesional procedure through which tremor can
      be successfully brought under control in 88% of the cases. Moreover, even the
      remaining PD symptoms can be targeted and successfully treated by
      neurostimulation.

PMID- 7571658
TI  - Early adolescent girls' understanding of menstruation.
AB  - Sixth grade girls (N = 224) were queried about their preparation for and
      expectations about menarche, their parents' roles in preparation, and their
      understanding of the biological basis of menstruation, characteristics of the
      menstrual cycle, menstrual hygiene, and menstrual-related physical and
      psychological changes. Although girls viewed themselves as prepared for menarche,
      and claimed they had discussed it with their mothers, their explanations of
      menstruation reflected at best incomplete knowledge, and more typically a variety
      of misconceptions or ignorance. In attempting to explain menstruation, they
      tended to focus on one particular element of the process (e.g., eggs or blood or
      the uterus), and were not able to integrate the elements into a comprehensive
      whole. Girls' knowledge of the location and function of reproductive structures
      was faulty, and most did not understand how they were interrelated. Girls
      associated a variety of negative physical and psychological changes with
      menstruation, indicating that although they had not yet learned the biology of
      menstruation, they already had learned and internalized the cultural stereotypes
      and myths about menstrual symptomatology. In view of reports of high levels of
      sexual activity, often at very young ages, and without protection, and the high
      risk for acquiring sexually transmitted diseases, the failure to adequately
      educate girls about their own anatomy and physiology has serious implications.

PMID- 7571659
TI  - Parental and work role salience, everyday problems, and distress: a prospective
      analysis of specific vulnerability among multiple-role women.
AB  - Hierarchical multiple regression analyses were used to model psychological
      distress and physical complaints among 106 working mothers experiencing chronic
      stressors. Moderator variables included parental and occupational role value and
      commitment as measured by the Life Role Salience Scales. Both concurrent and
      prospective relationships were examined by means of a two-wave longitudinal
      design. A specific vulnerability model was tested by aggregating stressors
      according to role domains and matching stress variables to role salience
      variables. The psychological salience of social role occupation was hypothesized
      to intensify the impact of role-related stressors. Multiple regression analyses
      partially supported a specific vulnerability model. Parental role commitment and
      occupational role value significantly interacted with corresponding role-related
      stressors in predicting prospective health outcomes.

PMID- 7571660
TI  - Alcohol expectancies and the personal and parental drinking patterns of women.
AB  - (1) Do the alcohol expectancies of women significantly differ based on their
      personal consumption and/or on their perceptions of parental alcohol abuse? (2)
      What is the relationship between perceived parental problem drinking and current
      expectancies about alcohol consumption? Subjects were 238 female college
      students, aged 18 to 52 years. Subjects completed the Children of Alcoholics
      Screening Test, the Alcohol Expectancy Questionnaire and rated the quantity and
      frequency of their current alcohol consumption. A 2 x 3 MANOVA revealed a
      significant main effect of personal consumption on all six alcohol expectancy
      domains. The more a woman drinks, the higher her expectancies, particularly for
      Increased Physical and Social Pleasure. A family history of parental alcohol
      abuse in general did not result in differences in personal consumption or in
      alcohol expectancies. However, women who felt personally responsible for their
      parents' alcohol abuse consistently reported higher Global Positive alcohol
      expectancies. The implications of these findings for the prevention and treatment
      of alcoholism in women are discussed.

PMID- 7571662
TI  - Self care actions of Colombian por dia domestic workers: on prevention and care.
AB  - This is a report of a phenomenological study of Colombia's "por dia" domestic
      workers that examined their actions in promoting their health, in preventing
      illnesses, and in caring for themselves. A cross sectional sample of 60 per diem
      female domestic workers in one large city in Colombia were interviewed using open
      ended interview questions about their health, self-care actions, health care
      resources, and patterns of utilization. We argue that knowledge of women's
      experiences with the health care system, their knowledge of their bodies, and the
      daily demands on their time and life are vital in defining and planning health
      care services that women need. We demonstrated that the structural conditions in
      and for health care services and the lack of knowledge of their bodies act as
      barriers to women's utilization of health care services and to maintaining their
      health. Our findings support the need for considering women's health from a
      development perspective and for offering more integrated and cohesive health care
      services for women.

PMID- 7571661
TI  - Oral manifestations of bulimia nervosa.
AB  - Bulimia nervosa is a psychological compulsive eating disorder that appears to be
      affecting a growing number of young women. It is characterized by repeated
      episodes of binge-eating followed by vomiting or some other purging behavior.
      Bulimia is accompanied by a number of physiological disturbances, some of which
      occur in the oral cavity. The present article reviews the major characteristics
      of bulimia nervosa, and describes the most significant oral manifestations of
      this disorder along with their reported incidences and etiologies.

PMID- 7571663
TI  - Comparison of cefotaxime plus metronidazole versus cefoxitin for prevention of
      wound infection after abdominal surgery.
AB  - In a randomized prospective stratified trial consisting of 1010 patients
      undergoing abdominal surgery involving the viscera, the efficacy of cefotaxime
      plus metronidazole was compared to cefoxitin for preventing wound infection. The
      efficacy of a single dose of antibiotics versus three doses over 24 hours was
      also evaluated. This study demonstrated that a single-dose antibiotic regimen was
      as effective as a multiple-dose regimen in the prophylaxis of wound infections
      following abdominal surgery. In addition it demonstrated that the cefotaxime plus
      metronidazole regimen is comparable to that of cefoxitin and is more cost
      effective. It is concluded that a single dose of cefotaxime plus metronidazole
      provides effective prophylaxis against postoperative wound infections following
      abdominal surgery.

PMID- 7571664
TI  - Male breast cancer: Austrian experience.
AB  - Data were collected on 169 men treated for breast cancer at 36 surgical
      departments in Austria between 1970 and 1991. We report here several of their
      clinical features and assess the importance of established prognostic factors.
      After a median observation period of 51 months 60 patients (35%) suffered a
      recurrence. The estimated 5-year recurrence-free survival for the entire group
      was 55%, and the estimated 5-year overall survival was 62%. Although stage
      adjusted data are comparable to those for female breast cancer, the outcome in
      this series may be attributed to a relatively high frequency of advanced tumor
      stages. Tumor size (recurrence-free survival p = 0.00001; overall survival p =
      0.03) and axillary lymph node status (recurrence-free survival p = 0.0001;
      overall survival p = 0.0001) proved to have a prognostic impact. Using a
      multivariate analysis, axillary lymph node status (recurrence-free survival p =
      0.001; overall survival p = 0.01) still had prognostic influence. The various
      procedures used had no effect on local recurrence.

PMID- 7571665
TI  - Hepatitis C virus infection among Japanese general surgical patients.
AB  - The incidence of hepatitis C virus (HCV) antibody positivity is unknown. The
      purpose of this study was to clarify the prevalence of HCV infection among
      surgical patients and to identify high risk surgical patients. HCV antibody tests
      were performed in 789 surgical patients between April 1991 and March 1992. Of
      these patients, 129 (16.3%) tested positive, which was much higher than the
      positivity of the ordinary Japanese. Hepatobiliary diseases and portal
      hypertension were associated with a higher positivity than other disease
      categories (94 of 206, 45.6% versus 35 of 583, 6%; p < 0.0001). Patients above 50
      years of age had a higher positivity than their younger counterparts (118 of 578,
      20.4% versus 11 of 211, 5.3%; p < 0.0001). The HCV positivity was as high as
      54.1% (119 of 220) among surgical patients with known risk factors for hepatitis,
      in contrast to only 1.9% (10 of 569) among those without such risk factors. We
      conclude that surgical patients have a high incidence of HCV infection, for whom
      medical professionals should pay special attention to avoid disease transmission.

PMID- 7571666
TI  - Reconstruction of the food passage after total gastrectomy: randomized trial.
AB  - Controversial results have been reported regarding the importance of the duodenal
      food passage after total gastrectomy. There are a number of experimental and
      clinical studies showing an advantage for the jejunal interposition between
      esophagus and duodenum. Others favor the Roux-en-Y reconstruction, as it is
      technically less demanding. The purpose of this study was the randomized
      comparison between two major reconstruction principles after total gastrectomy
      for gastric cancer (i.e., jejunal interposition with pouch versus Roux-en-Y pouch
      reconstruction). A group of 120 patients with gastric cancer were randomized and
      operated on during a 5-year period according to standardized operative protocols,
      using either a jejunal interposition with pouch (JIP) or the Roux-en-Y
      reconstruction with pouch (RYP). Endpoints of this study were operation time,
      intra- and postoperative problems and complications, patients' body weight,
      functional assessment, and quality of life. Of the 120 patients, 14 had to be
      withdrawn during the operation because only the Roux-en-Y reconstruction was
      technically possible. Finally, 53 patients with JIP were compared with 53
      patients with RYP for the perioperative course. There were no significant
      differences between the two procedures (RYP and JIP) regarding complications
      (24.5% and 26.4%, respectively), mortality (3.8% and 1.9%, respectively), and
      operation time (4.35 hours and 4.40 hours, respectively). For long-term
      functional comparison 46 (RYP, n = 26; JIP, n = 20) patients were without
      recurrence after 3 years of survival. Comparison of body weight, Visick scoring,
      and the Spitzer Index also did not reveal any significant difference between the
      two operation methods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571667
TI  - Survival after resection of gastric cancer and prognostic relevance of systematic
      lymph node dissection: twenty years experience in Taiwan.
AB  - A retrospective study of 954 resectable gastric cancers in a single institute of
      Taiwan from 1971 to 1990 was performed to evaluate improvements in gastric cancer
      surgery. The patients were divided into four time periods representing an overall
      experience of progressive implementation of aggressive resection and increased
      extent of systematic lymph node dissection. The clinicopathologic data and
      survival rates were statistically compared and the significance of the extent of
      resection on survival analyzed. A significant increase in the proportion of upper
      one-third tumors (from 14.8% to 20.4%) and a decrease in the incidence of
      intestinal type (73.6% to 41.5%) was found within the overall period. The
      proportion of patients with early gastric cancer increased from 11.5% to 19.4%.
      Patients who underwent total gastrectomy and combined visceral resection
      increased from 13.7% to 27.4% and 19.8% to 41.1%, respectively. An increase of
      both total dissected lymph node number and the incidence of detected lymph node
      metastases in early gastric cancer were associated with more extensive
      lymphadenectomy. An improved 5-year survival rate following aggressive resection
      was found for all stages except stage IV and T4 lesions, and the surgical
      mortality decreased from 5.5% to 2.0%. Patients with earlier stage lesions
      benefited more from radical resection, especially those with stage II and T2
      lesions. Systematic lymph node dissection increased the 5-year survival of
      patients by about 10% for stage III or T3 lesions but not for patients with stage
      IV or T4 lesions. Multivariate analysis confirmed the significance of the
      improved technique of lymphadenectomy on the prognosis of gastric cancer
      following resection in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571668
TI  - Diaphragmatic or transdiaphragmatic thoracic involvement in hepatic hydatid
      disease: surgical trends and classification.
AB  - We performed a retrospective study of 19 patients who had been operated on for
      hepatic hydatid disease with diaphragmatic or transdiaphragmatic (D-TD) thoracic
      involvement chosen from a total of 444 patients who underwent operations for
      hepatic hydatid disease. In all cases D-TD involvement was confirmed by
      ultrasonography, CT, or MRI scan. We propose a new classification (grades 1-5)
      based on the degree of development of D-TD involvement. Before 1984 exposure was
      obtained by thoracophrenolaparotomy (nine cases) and later by right subcostal
      incision. Only four patients required atypical pulmonary resection. In 13 cases
      the diaphragm was repaired, and all 24 hepatic cysts were treated with total (16
      cases) or partial (8 cases) cystopericystectomy. There was no operative
      mortality, and the most serious morbidity consisted of a biliary fistula and a
      biliobronchial fistula. For treatment of these patients we recommended right
      subcostal incision and total or near-total cystopericystectomy as a first choice
      of surgical technique.

PMID- 7571671
TI  - Symptomatic duodenal diverticulum.
AB  - To determine management guidelines for symptomatic duodenal diverticulum, we
      reviewed medical records of 26 patients. Complicated duodenal diverticulum was
      the only possible cause of symptoms-abdominal pain, fever and chills, melena,
      vomiting-in 18 patients. Ten patients improved with conservative management, and
      eight patients underwent diverticulectomy with or without various other
      procedures. Among the eight patients, one patient who had duodenal fistula died
      of respiratory complications on the second postoperative day. Symptoms recurred
      in two patients: One had a distal common bile duct (CBD) stricture and underwent
      choledochojejunostomy. In the other patient a CBD stone developed 3 years later,
      and choledocholithotomy and choledochojejunostomy were performed. Eight patients
      had associated gallstone disease as well as the diverticulum. Five of the eight
      had a history of operation for gallstone disease; four improved with conservative
      treatment, and one underwent choledochojejunostomy. Two patients were thought to
      have an innocent diverticulum and underwent cholecystectomy and
      choledocholithotomy only. One patient underwent diverticulectomy and
      sphincteroplasty for a CBD stone and pervaterian diverticulum. In conclusion,
      operations for duodenal diverticulum should be reserved for seriously complicated
      diverticula, and the surgeon should be aware that pervaterian diverticulum can be
      a cause of choledocholithiasis.

PMID- 7571670
TI  - Laparoscopic surgery of hepatic hydatid disease: initial results and early follow
      up of 16 patients.
AB  - Surgery is the main modality in the treatment of hepatic hydatid disease. In this
      report, a laparoscopic surgical method is described, and the results in the first
      16 cases are presented. The method involves the use of an aspirator-grinder
      apparatus that achieves effective evacuation of viable cyst contents with the
      patient benefiting from the laparoscopic approach. Cavity infection occurred in
      two patients and was treated conservatively. In another patient, postoperative
      ultrasonography revealed a thick-walled cavity containing a dense fluid. Because
      the patient was symptomatic, pericystectomy was performed during the sixth
      postoperative month. Early postoperative parameters and the early follow-up
      results in other patients (2-17 months) are encouraging. The method is
      particularly suitable for uncomplicated, early-stage cysts located in
      laparoscopically accessible locations.

PMID- 7571669
TI  - Management of intrabiliary rupture of hydatid cyst of the liver.
AB  - Thirty-six patients with intrabiliary rupture of hepatic echinococcal cysts were
      managed between 1974 and 1993. Clinical findings, skin tests, serologic tests,
      and imaging techniques were used to establish the diagnosis. Twenty-five (69.4%)
      patients had pain, 24 (66.6%) jaundice, 22 (61.1%) fever, 20 (55.5%) chills, 10
      (27.7%) malaise, and 7 (19.4%) other symptoms as the major causes of admission.
      All patients underwent choledochotomy and T-tube drainage. Treatment directed to
      the cyst was cystectomy and capittonage, cystectomy and drainage, and partial
      hepatectomy in 22, 12, and 2 patients, respectively. Omentoplasty was added to
      the treatment in 10 patients. Seven (19.4%) patients had complications. The
      period of hospitalization for patients with and without complications was 34.6 +/
      18.1 and 15.1 +/- 2.7, days, respectively. This study indicates that better
      results are obtained in patients with cystic lesions of the liver by avoiding
      percutaneous puncture or biopsy, the early use of ultrasonography and computed
      tomography, evacuation of the cyst together with its germinative membrane and the
      involved biliary tract under adequate care to avoid spillage into the peritoneal
      cavity, treating the remaining cavity according to its location, size, and the
      presence of infection, and decreasing the pressure in the biliary tract by T-tube
      drainage.

PMID- 7571672
TI  - Meckel's diverticulum in Amsterdam: experience in 136 patients.
AB  - The object of this study was to establish the relation of symptomatic diverticula
      to the age and gender of the patients and to the presence of ectopic tissue. A
      total of 136 patients with surgically treated diverticula were collected from the
      medical charts of five Amsterdam hospitals; 51 had undergone resection because of
      diverticulum-related symptoms and 85 during laparotomy for other causes.
      Obstruction was the predominant symptom (39%) in the 51 symptomatic patients.
      Hemorrhage, perforation, diverticulitis, and intussusception were the other
      symptoms (12-14% each). Obstruction occurred mainly in patients under age 10
      years and perforation in patients 10 to 30 years old. All symptoms, hemorrhage
      excepted, occurred two to four times more in men. Hemorrhage and perforation were
      associated with the presence of ectopic gastric tissue. We concluded that
      symptoms caused by Meckel's diverticula are mainly due to the presence of bands
      or ectopic gastric tissue. The symptoms manifest at an early age (77% in those
      under age 30) and predominantly in males. Diverticula found incidentally in
      patients younger than 30 years should be resected. In the older patients,
      resection is indicated if ectopic gastric tissue is suspected. Diverticular bands
      can simply be cut.

PMID- 7571674
TI  - Video-assisted endoscopic esophagectomy with stapled intrathoracic
      esophagogastric anastomosis.
AB  - Thoracic esophagus was usually removed through the transhiatal approach or via an
      open thoracotomy. The long incision and spreading of the ribs usually resulted in
      much pain and interference with chest wall mechanics. Today, with the development
      of a video-assisted endoscopic procedure, many intrathoracic lesions can be
      removed through small incision. Since March 1992 we have attempted 20
      esophagectomies and reconstruction using a right thoracoscopic approach in 16
      males and 4 females whose average age was 56 years. Indications for its use were
      esophageal cancer in 17 patients (squamous cell carcinoma in 12 patients,
      adenocarcinoma in 5) and caustic stenosis in 3. It is our impression that video
      assisted endoscopic esophagectomy and reconstruction potentially causes less
      trauma, less postoperative discomfort, and a rapid functional recuperation. Our
      initial experiences showed that it is a feasible, effective procedure.

PMID- 7571675
TI  - Coelioscopic cholecystectomy: experience with 2006 cases.
AB  - 2006 laparoscopic cholecystectomies (LC) were performed from April 1988 to
      December 1992 by three senior surgeons using the French technique and selective
      intraoperative cholangiography (IOC). Obesity was present in 318 patients
      (15.8%), respiratory insufficiency in 75 (3.7%), inflammation in 251 (12.5%), and
      common bile duct (CBD) stones in 83 (4.1%). The presence of these additional
      ailments is a good indication for LC. Conversion to laparotomy occurred in 43
      cases (2.1%). The rate of complications was 2%; 25 (1.25%) were nonbiliary
      complications and 15 (0.7%) were biliary-related; there was one death. IOC is not
      effective in preventing biliary complications, as those observed in this study
      would not have been recognized or avoided by it. IOC is carried out only
      selectively to locate unsuspected stones in patients with risk factors of CBD
      lithiasis. Laparoscopic treatment of CBD stones is still controversial.

PMID- 7571673
TI  - Antioxidative vitamin treatment: effect on lipid peroxidation and limb swelling
      after revascularization operations.
AB  - The objective of this study was to evaluate the antioxidative properties of the
      multivitamin cocktail Omnibionta (alpha-tocopherol, ascorbic acid, retinol,
      vitamin B complex) in terms of diminishing lipid peroxidation with improvement of
      leg edema performance after limb revascularization operations in humans. Fifty
      one subjects were selected; the control group contained 27 patients and the
      treatment group 24 patients, who received the vitamin cocktail intravenously
      before the start of reperfusion. All patients suffered from acute or chronic
      arterial occlusive disease, except two subjects with arterial trauma. MDA-TBARS
      in plasma, quantified by HPLC, taken as a measure of lipid peroxidation was
      significantly increased (p < 0.001) in the control group 1 hour after reperfusion
      onset and decreased to its baseline value within the following 2 hours (0.73 +/-
      0.26, 1.21 +/- 0.48, 0.99 +/- 0.48, 0.73 +/- 0.33 nmol/ml). In contrast, in the
      treatment group MDA-TBARS did not exceed the baseline value during the
      reperfusion period (0.93 +/- 0.30, 0.70 +/- 0.29, 0.65 +/- 0.23, 0.70 +/- 0.37
      nmol/ml). Leg edema, expressed by extremity circumference, was significantly (p <
      0.008) elevated in the control group (30.7 +/- 4.04 cm versus 35.35 +/- 4.12 cm)
      compared to a lack of increase in the treatment group (29.25 +/- 5.13 cm versus
      29.76 +/- 5.70 cm). These results suggest that antioxidative vitamin treatment
      might be valuable in preventing lipid peroxidation and decreasing extremity
      edema.

PMID- 7571676
TI  - Outcome of 49 repairs of bile duct injuries after laparoscopic cholecystectomy.
AB  - Treatment of bile duct injuries after laparoscopic cholecystectomy is still under
      discussion. The aim of this study was to evaluate the results of end-to-end or
      biliodigestive anastomosis for various types of bile duct injury. Patient charts
      of 49 (0.81%) classified bile duct injuries from a national survey of 6076
      laparoscopic cholecystectomies in The Netherlands were analyzed. The median
      follow-up after repair was 183 days (range 14-570 days). Statistical analysis
      showed that an end-to-end anastomosis was preferred by the surgeons for less
      severe bile duct injuries and a biliodigestive repair for more severe injuries.
      Three patients died owing to a delayed detected bile duct injury. Twelve bile
      duct strictures occurred after repair, leading to a stricture rate of 25%. The
      time elapsed between repair and occurrence of a stricture was 134 days (range 13
      270 days). The type of repair or the severity of the bile duct injury did not
      determine the outcome of the repair. Histologically proved cholecystitis
      predisposed a stricture at the repair site. It was concluded that treatment of
      bile duct injuries is associated with a high stricture rate at the repair site of
      the anastomosis. End-to-end anastomosis is mostly successful for the less severe
      injury detected during laparoscopic cholecystectomy. For all other cases this
      repair can at least be considered a temporary internal drainage procedure. The
      biliodigestive anastomosis can best be considered a delayed repair after a
      drainage procedure has resolved the local inflammatory status.

PMID- 7571677
TI  - Extended cholecystectomy for carcinoma of the gallbladder.
AB  - We evaluated extended cholecystectomy, wedge resection of the gallbladder bed,
      and regional lymphadenectomy for carcinoma of the gallbladder. Between 1971 and
      1993 we treated 227 patients, 59 of whom were treated with simple cholecystectomy
      and 66 with extended cholecystectomy. The tumors were classified according to the
      stages proposed by the Japanese Society of Biliary Surgery. For Stage I and II
      disease extended cholecystectomy had a better result than simple cholecystectomy.
      For the extended cholecystectomy cases the cumulative 5-year survival rate was
      78.9% for Stage I, 63.6% for Stage II, 44.4% for Stage III, and 8.3% for Stage
      IV. The survival of Stage I patients was excellent. For cases more advanced than
      Stage II (S3, N2, Hinf1, and Binf1), the prognosis was significantly worse. In
      these cases more aggressive surgery may be needed.

PMID- 7571678
TI  - Clinical experience with the intrahepatic posterior approach to the portal triad
      for right hepatectomy and right segmental resection.
AB  - An intrahepatic posterior approach to the portal triad has been used over a 2
      year period to perform right hepatectomies and right segmental resections in 29
      patients (20 men, 9 women; median age 63 years, range 22-82 years). Two
      resections were palliative for cholangiocarcinomas; the remainder included 9
      hepatocellular carcinomas, 12 colorectal metastases, 2 adenomas, 3 cancers of the
      gallbladder, and one case of chronic hepatic fibrosis. The median operative time
      was 3 hours 40 minutes (3:40; range 2:20-7:00) with a median period of hepatic
      ischemia of 87 minutes (range 27-152 minutes). Median blood transfused was 0 unit
      (range 0-12 units) with only three patients requiring intensive care admission.
      There was one hospital death. All but one patient was followed up after surgery
      (median period 24 months; range 1-36 months) at which time there had been three
      deaths from metastatic disease; the remaining patients were free of clinical
      recurrence. This operative approach allows minimally resective surgery to be
      performed safely with excellent short- and medium-term results.

PMID- 7571679
TI  - Effect of hepatic artery chemotherapy on survival of patients with hepatic
      metastases from colorectal carcinoma treated with cryotherapy.
AB  - Thirty-eight patients with unresectable multiple liver metastases from colorectal
      carcinoma were treated with either hepatic artery chemotherapy (HAC) and
      cryotherapy (n = 27) or cryotherapy alone (n = 11). Follow-up survival data were
      summarized using Cox regression. Allowing for the effect of the pathology of the
      primary tumor and the preoperative carcinoembryonic antigen (CEA) level, those
      patients who did not receive HAC after cytoreduction were three times as likely
      to die as those given HAC (RR 3.3, 95%; CI 1.2-9.3). The estimated median
      survival of patients treated with cryotherapy alone was 245 days, whereas for
      those given more than 3 months of HAC plus cytoreduction therapy it was 570 days.
      It is recommended that all patients who receive cryotherapy for multiple liver
      metastases from colorectal rectal carcinoma be given subsequent hepatic artery
      chemotherapy.

PMID- 7571685
TI  - Mediation and peer review services.

PMID- 7571684
TI  - SMS physician support program.

PMID- 7571683
TI  - Statewide Physician Health Program.

PMID- 7571682
TI  - Influence of medical economics.

PMID- 7571681
TI  - Doctor, you're needed away from the bedside.

PMID- 7571686
TI  - Informing breast surgery patients about treatment options.

PMID- 7571680
TI  - Electrorectography in chronic constipation.
AB  - The rectal electrical activity recorded by electrorectogram (ERG) was studied in
      22 chronically constipated subjects and 16 healthy volunteers. The latter had a
      mean (+/- SD) age of 42.6 +/- 8.5 years; 10 were men and 6 women. Of the 22
      constipated patients, 14 had inertia-type constipation (IC; age 44.6 +/- 10.2
      years) and 8 the obstructive type (OC; age 38.4 +/- 12.2 years). The rectal
      electrical activity was recorded by a silver-silver chloride electrode situated 1
      cm from the tip of a 6 F catheter, which was applied to the rectal mucosa by
      suction. At least four recording sessions of 120 minutes each were performed for
      each individual. In normal volunteers, regular and reproducible pacesetter
      potentials (PPs) were recorded with a mean frequency of 2.8 +/- 0.7 cycles/min
      (cpm), amplitude 2.1 +/- 0.8 mV, and velocity 4.6 +/- 0.8 cm/sec. They were
      followed randomly by action potentials (APs). In IC patients the PPs were so
      infrequent that in most cases half an hour would have elapsed without recording a
      PP; the mean frequency was 2.4 +/- 0.2 cycle/60 min, amplitude 0.92 +/- 0.02 mV,
      and velocity 4.1 +/- 0.6 cm/sec. APs were not recorded in 10 patients during the
      recording time; in two patients they were occasional. In OC subjects regular and
      reproducible PPs were recorded with a higher frequency (p < 0.01) and velocity (p
      < 0.05) than normal. Two ERG patterns were identified in those with chronic
      constipation: bradyrectia and tachyrectia. The former was recorded in the IC
      subjects and the latter in OC subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571687
TI  - Medicine, money, and morality....

PMID- 7571688
TI  - EVP report: the view from here. Restructuring Medicare or resurrecting the lost
      covenant.

PMID- 7571689
TI  - Malignant gastroesophageal polyp: a case report.
AB  - This case illustrates the entity of esophagealadenocarcinoma presenting in an
      esophageal polyp. Esophageal polyps are rare. The clinical presentation,
      diagnostic evaluation, pathophysiology, and treatment are discussed.

PMID- 7571690
TI  - Ketorolac-induced postoperative acute renal failure: a case report.
AB  - The nephrotoxic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are well
      recognized. Known potentiating risk factors include pre-existing renal disease,
      intravascular volume depletion, and concomitant administration of other
      nephrotoxic drugs. We present a case report of renal failure following short term
      usage of intramuscular ketorolac (Toradol) in a patient with no known risk
      factors who underwent an uncomplicated laparotomy. The literature concerning
      ketorolac-induced renal failure is reviewed and physicians are reminded to be
      aware of this potential complication.

PMID- 7571691
TI  - Cardiovascular disease prevention projects in local public health agencies,
      Wisconsin, 1995.

PMID- 7571692
TI  - The disruptive-abusive physician: a new look at an old problem.

PMID- 7571693
TI  - Initial management of community-acquired pneumonia.

PMID- 7571694
TI  - WIC update: the physician's role in helping families, pregnant women obtain good
      nutrition.

PMID- 7571696
TI  - Pillowtalk.

PMID- 7571695
TI  - Tort reform converts.

PMID- 7571697
TI  - Screening for risk of malnutrition in Wisconsin's elderly.
AB  - In older adults, nutritional status is related to chronic disease risk, ability
      to maintain independent lifestyles, and rate and duration of hospitalizations.
      Significant numbers of American elders are either malnourished or at risk of
      malnutrition. Data from a recent survey of 21,000 Wisconsin participants in home
      delivered or congregate meals 60 years of age and older indicated that in this
      group, over one fourth were at high risk for malnutrition. The Nutrition
      Screening Initiative, a collaborative effort of the American Academy of Family
      Physicians, the American Dietetic Association, and the National Council on the
      Aging, has identified risk factors for malnutrition in the elderly and is
      promoting systematic nutrition risk screening and intervention within the health
      care system. Risk factors for malnutrition in older adults, screening techniques
      available to medical practices, and resources for intervention are described in
      this paper.

PMID- 7571698
TI  - Evaluation for surgical treatment of partial epilepsy: an overview.
AB  - When a focal epilepsy proves refractory to medical therapy, surgical treatment is
      available and increasingly used. Most interventions consist of focal cortical
      resections, and by far the most common operation is a temporal lobectomy. The
      presurgical evaluation is complex and multidisciplinary. It includes clinical
      evaluation, EEG-video monitoring, neuropsychological testing, and structural as
      well as functional imaging. When surface EEG fails to identify the epileptogenic
      zone with sufficient confidence, several invasive methods are available, each
      with its advantages and limitations. In addition to neurophysiologic data, when
      there is convergence of structural imaging (MRI) and functional testing (Wada
      test, neuropsychological evaluation, nuclear imaging), a single focus can be
      identified, and a focal resection is likely to be successful. Surgery is a well
      accepted and effective therapeutic modality for patients with refractory
      epilepsy. When surgical candidates are selected appropriately, results are
      excellent, especially for temporal lobe epilepsy.

PMID- 7571699
TI  - Palliative medicine education at the Medical College of Wisconsin.
AB  - Palliative medicine is an emerging worldwide discipline. This article describes
      efforts at the Medical College of Wisconsin to develop programs to enhance
      palliative care education and clinical care. New courses, seminars, and clinical
      programs have been developed with assistance from various medical school
      departments and affiliated hospitals. Education and clinical care activities
      since 1990 have included a new 6-week course for 2nd-year medical students; a
      hospice volunteer experience for preclinical students; clinical electives for 3rd
      and 4th-year medical students; a clinical palliative care consultation service;
      a palliative care seminar series designed for housestaff; a nurse preceptorship
      program; and an allied health observership program. Palliative care activities
      include both the academic medical center and community health agencies. The MCW
      has integrated palliative care into its academic environment so that trainees at
      all education levels now have opportunities for didactic and clinical palliative
      care education.

PMID- 7571700
TI  - The debate over physician-assisted suicide.

PMID- 7571701
TI  - A breast and cervical cancer screening intervention at public health influenza
      clinics, Dane County, Wis.

PMID- 7571702
TI  - China: lowering maternal mortality in Miyun County, Beijing.
AB  - In Miyun County in China the medical authorities registered an elevated maternal
      mortality ratio which needed to be verified in order to design corrective
      changes. A decision was taken in 1988 to start a project of pilot interventions
      in the organization of maternal health services and access for obstetric
      emergencies. A control and pilot area were chosen in order to test the validity
      of the interventions. The reduction in maternal mortality from the main
      complications (postpartum haemorrhage and eclampsia) was impressive and no more
      maternal deaths were registered in the pilot area with reference to these causes.
      The overall maternal mortality ratio per 100,000 live births dropped by more than
      75% in the pilot area throughout the three-year implementation period. It was
      therefore shown that the synergistic effect of additional training of medical
      workers and traditional birth attendants, improved health education, the
      provision of easier access to emergency care services, the establishment of
      obstetric rescue teams at the county level, generally improved MCH services, and
      strengthened management capacity for high risk pregnancies were the most
      appropriate interventions to lower maternal mortality.

PMID- 7571703
TI  - Ethiopia: an epidemiological study of vesico-vaginal fistula in Addis Ababa.
AB  - A 10% sample was drawn from 3000 records on vesicovaginal fistulae operations
      performed at the Addis Ababa Fistula Hospital for Poor Women with Childbirth
      Injuries and their content were analyzed. In 88% of the cases under review the
      operation was classified as successful. The results of this study underline the
      tremendous maternal health gains which can be achieved by appropriate obstetric
      care in case of obstructed labour. It also reinforced the need for early
      detection and referral of high risk births among the very young mothers who are
      likely to experience an obstructed labour, the loss of the child, vesico-vaginal
      fistulae and possibly a ruptured uterus. In the absence of likely increases in
      the availability of transport, the building of waiting homes at maternal clinics
      is encouraged so that women can await delivery in the vicinity of a referral
      centre. There is a need for increased attendance of delivery by trained personnel
      as well as for continuing education for both staff and traditional birth
      attendants. It is further recommended to train former patients as helpers for the
      dedicated care which needs to be extended to the unfortunate, and often
      stigmatized victims.

PMID- 7571705
TI  - Maternal health and safe motherhood: findings from concluded research studies.

PMID- 7571704
TI  - Gambia: evaluation of the mobile health care service in West Kiang district.
AB  - A project to improve the quality of maternal health services was carried out over
      a 3-year period in West Kiang district, Gambia. Coverage of maternal care was
      strengthened through upgrading of personnel, TBA training, improved treatment and
      referral schemes, and increased numbers of visits to rural outreach areas. A
      control district was used to compare the impact of the interventions. During the
      project period of 3 years a single maternal death was registered in the
      intervention district, and 5 in the control area. While improved staffing and
      service provision led to higher degrees of coverage of maternal care services,
      reductions in maternal morbidity could not be documented in the intervention
      area. Given concern over the quality of the data possibly influencing this
      result, further research is necessary to determine the relationship between
      improved mobile maternal care services and their impact on maternal morbidity and
      perinatal outcome.

PMID- 7571706
TI  - The Gambia: cost and effectiveness of a mobile maternal health care service, West
      Kiang.
AB  - A relatively small body of knowledge has been generated in the past to identify
      the cost-effectiveness of mobile versus static clinics, or combinations thereof.
      The changes introduced by the new mobile maternal health care service offered an
      opportunity to address the issue of cost-effectiveness of changes introduced to a
      specific geographical area. Considerably higher total costs were incurred,
      particularly as a result of increased training and staffing. However, evidence
      (Foord, 1993) has shown that several key measures of process eg. number of
      haemoglobin tests taken and haemoglobin levels increased significantly. Therefore
      the extra expenditure created clear service improvements. Linking such changes to
      reductions in mortality was more difficult as the population size and rarity of
      maternal deaths made it difficult to show statistically significant differences.
      The results should only provide part of the information required by decision
      makers, for a number of reasons. First, this cost-effectiveness analysis provided
      no information regarding any form of equity. Secondly, many factors affect cost
      effectiveness ratios and further investigation of the organisation and management
      of the mobile service may highlight further room for improvement within the
      service itself, thus improving the efficiency. In this case there were grounds
      for re-assessing costs in relation to training, undertaking an assessment of
      staffing needs and increasing accountability in the use of resources. This study
      gives detailed information on the structure of costs for a mobile unit. It is
      unusual in its consideration of how a mobile team fits into the structure of
      existing health services and implications of provision on other levels of
      service.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571707
TI  - Guatemala: maternal mortality in Guatemala: assessing the gap, beginning to
      bridge it.
AB  - Developing countries which have somewhat reliable vital statistics but poor or
      incomplete information about maternal mortality must make the most of the data
      available. Such data may require modification for maternal mortality analyses.
      What is important, however, is the decision to use available information and to
      analyse it properly. The analysis of maternal mortality in Guatemala, using data
      from 1986 birth and death certificates, identified particular areas, health
      regions, and particular ethnic groups that had significantly higher maternal
      mortality ratios than others. Small but disproportionately affected populations
      that had no available maternal health assistance were identified-a problem found
      in many developing countries. These groups urgently need the services of
      traditional birth attendants or other forms of assistance before, during and
      after delivery. The analysis of vital statistics led to the beginning of
      operative research and the collection of background information for establishing
      an epidemiologic surveillance programme for maternal mortality.

PMID- 7571708
TI  - Guinea-Bissau: maternal mortality assessment.
AB  - With more than 40% of all female deaths attributable to pregnancy, delivery, and
      the puerperium period, the study established a maternal mortality ratio of 914
      deaths per 100,000 live births. The principal risk factors for dying from
      pregnancy-related causes are: no attendance at antenatal care, too great a
      distance between the home and the nearest hospital facility, home delivery,
      belonging to specific ethnic/religious groups, and delivery assistance from
      family members and TBAs. The health policy implications to improve this situation
      are: increased coverage with appropriate services, increased numbers of rural
      midwives, in-service training of existing staff in maternity issues and problems,
      culture-specific educational approaches using the existing value system,
      educational campaigns to discourage harmful practices and behaviour, continued
      educational efforts to upgrade the knowledge of TBAs, and a culturally sensitive
      integration of TBAs into the government programmes.

PMID- 7571709
TI  - Guinea-Bissau: what women know about the risks--an anthropological study.
AB  - The study examined the range of traditional and spiritual concepts surrounding
      pregnancy and childbirth. Most of these beliefs and practices prevent appropriate
      nutrition, antenatal, and delivery care. Knowledge of danger signs and risk
      factors is virtually absent. When illness becomes manifest the women tend to
      consult competing sectors of traditional and modern medicine, but no referral or
      cooperation exists between them. The perceived curative orientation of antenatal
      service results in their underutilization. The study findings reinforce the need
      to develop appropriate health education programmes to overcome prevailing
      prejudices towards the modern health sector and covering a wide range of health
      education topics, including danger signs in pregnancy and the accompanying
      antenatal and delivery care. The integration of traditional practitioners into
      the existing primary health care system should be encouraged. The modern sector
      would benefit from the upgrading of personnel, equipment, and drugs as well as
      the development of integrated maternal and child health and family planning
      services. Continuous education should help nurses and midwives to become more
      responsive to the special needs of pregnant women and to provide family planning
      education. Outside the health sector, school health education should include sex
      education in order to avoid unwanted, early pregnancies. Finally the health
      information system should be improved to provide accurate information on
      pregnancy related morbidity and maternal mortality.

PMID- 7571711
TI  - The Lao People's Democratic Republic: maternal mortality and female mortality:
      determining causes of deaths.
AB  - A sample of 380 female deaths in the age group 15-49 years from 16 provinces of
      the Lao People's Democratic Republic were analyzed to determine the most likely
      cause of death. 127 deaths were classified as maternal, 28% occurred during
      pregnancy and the remaining 72% within six weeks of the termination of pregnancy.
      Almost three quarters of all maternal deaths were directly related to obstetrical
      complications during pregnancy or childbirth. Many of these deaths could probably
      have been avoided, if appropriate obstetric care had been available. The level of
      attention to problems related to maternity and childbirth needs to be raised at
      all responsible levels of the health service system. This must start at the
      health facility where attending nurses and midwives should be oriented towards
      pregnancy-related problems and early detection of high-risk women, with
      appropriate supervisory support. District and national administrations should
      also focus more on maternity services within their Primary Health Care programme.

PMID- 7571710
TI  - Argentina: risk factors and maternal mortality in La Matanza, Province of Buenos
      Aires, 1990.
AB  - An evaluation of the health services infrastructure of the La Matanza part of
      Buenos Aires in 1990 was carried out in addition to an evaluation of maternal
      mortality case studies. This procedure allowed for an assessment of factors
      related to the performance of health services and the health behaviour of women
      which, concomitantly, led to maternal deaths. Approximately 50% of maternal
      deaths went unreported in La Matanza on the basis of record checks performed in
      the institutions, hence the maternal mortality was twice as high as officially
      indicated for 1990. Flaws in the proper clinical diagnosis of the causes of
      deaths were detected and a higher degree of precision was called for. In the case
      of women who came from the poorest section of La Matanza, most deaths were due to
      complications related to abortion (either self-induced or non-professionally
      induced). Most of the maternal deaths could have been avoided. The sociological
      enquiry revealed conflicting social pressures which led the women onto the path
      of maternal death. The men were found not to be involved in the health issues
      arising from pregnancy and delivery, and the reproductive process was seen to lie
      exclusively in the women's domain. The services were not prepared to cater for
      the needs of poor women, and the inadequacy of the existing system to reach the
      women in need was well documented. Detection of women at risk was lacking in most
      establishments and, with the exception of one hospital, referral procedures did
      not exist. At the municipal level the absence of a policy for maternal and child
      health was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571712
TI  - Mexico: maternal deaths, fertility patterns, and social cost--an anthropological
      study.
AB  - The study of life histories of women who died from a maternal causes identified a
      lack of value attached to the care of the pregnant woman as one of the main
      constraints to the prevention of maternal mortality. The immediate family members
      and women who died had considered pregnancy as a "natural" event. Maternal
      complications were not perceived as meriting appropriate medical attention. This
      negative scenario combined with rivalry between providers of traditional and
      modern medical care, led to a passivity which ultimately prevented appropriate
      maternal care. These social and cultural values, which reinforce the lack of
      attention given to pregnant women call for educational efforts on the part of
      community leaders and health service providers to change the perceptions of
      pregnancy and childbirth as a completely "natural" event which needs little
      health care attention. The conflict between traditional birth attendants and the
      medical profession needs to be addressed by the respective authorities and
      educational solutions must be identified to rectify the existing lack of
      knowledge amongst TBA's. The question of developing a frame-work for
      collaboration between the traditional and the modern sector of health care will
      need to be addressed in the future.

PMID- 7571713
TI  - Pakistan: the Faisalabad Obstetric Flying Squad.
AB  - The Faisalabad Obstetric Flying Squad was established in 1988 and provides access
      to emergency obstetric services for the poor women of Faisalabad. The service is
      highly appreciated by both women and participating dais. The latter receive
      training from the Mother and Child Welfare Association of Faisalabad and form an
      integral part of the obstetric care team. While problems in accessing
      communication facilities exist, the project has made a lasting impact on the
      provision of emergency obstetric services in the city. Improved recording and
      reporting mechanisms would permit a more precise assessment of the impact of the
      service on the reduction of maternal morbidity and mortality. It would also
      permit an assessment of the operating costs of the service. One of the reasons
      the service functions effectively is that it is fully integrated into the general
      operations of the Allied Hospital. If similar institutional mechanisms can be
      established there is good reason to think that the Faisalabad Obstetric Flying
      Squad could be replicated in other developing country settings.

PMID- 7571714
TI  - Pakistan: consumer satisfaction and dissatisfaction with maternal and child
      health services.
AB  - The attitudes of a sample of 800 urban and 400 rural women towards pregnancy
      services and delivery care in Sindh province, Pakistan, were surveyed. The sample
      consisted of predominantly poor and illiterate women of reproductive age.
      Generally little access to quality institutional care services existed in the
      rural areas. Most rural women delivered at home using the services of the
      traditional midwife, the dai. Concern for costs and convenience was found to be
      coupled with a high degree of trust in the services of the dai. In the urban
      setting preference for the dais' services was likewise expressed, but the
      hospital was considered the safest place for delivery by the majority of
      respondents. The quality of the services rendered by all occupational groups was
      considered highly, in particular those of the traditional dais. The absence of
      trained doctors in the rural areas is noted and changes to increase their
      availability and services are proposed.

PMID- 7571715
TI  - Sudan: situational analysis of maternal health in Bara District, North Kordofan.
AB  - A high maternal mortality ratio was estimated in Bara District in Sudan during
      the late 1980's with approximately 407 women dying per 100,000 live births. In
      order to design effective intervention strategies, Care International and the
      Ministry of Health in Sudan conducted a study to identify the attitudes of women,
      staff, and TBAs towards motherhood, prenatal care, and practices affecting the
      health of women in the district. The previously conducted training programme for
      TBAs was also assessed in its impact. The study yielded the following results: in
      addition to the commonly known risk factors for maternal health e.g. haemorrhage,
      puerperal infection, obstructed labour, and anemia, the women in the villages and
      health staff identified female genital mutilation (pharaonic circumcision) as a
      major threat to safe motherhood. Health seeking behaviour was linked to problems
      of access and perceived quality of care: women did generally not wish to spend
      more than 30 minutes for reaching a facility. But if the quality of a particular
      institution was considered good, and supplies and equipment were available, women
      would cover great distances to reach such a facility. Participation in prenatal
      care suffered from the equation of preventive with curative care. Women would
      therefore tend to turn to a clinic or service provider, if symptoms of illness
      occurred during a pregnancy. The village-based services suffered from the lack of
      equipment and poor staff training, which further undermined the motivation to
      seek prenatal care. When health staff recommended referral of a pregnant women
      for delivery, the advice was usually followed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571716
TI  - China: epidemiology of pregnancy-induced hypertension.
AB  - The study of 67,813 pregnancies and their outcome confirmed the intrinsic
      negative impact of hypertension on pregnancy and childbirth. Measures to overcome
      the differences in hypertensive experience of rural as opposed to urban women lie
      in the expansion of the maternal and child health services in the rural areas.
      Maternity care services need to increase early detection of hypertension, improve
      monitoring of anticipated twin deliveries, enhance nutrition, reduce anaemia and
      other known risk factors and improve health education.

PMID- 7571717
TI  - Small intestinal sulphoxidation of albendazole.
AB  - 1. The in vitro sulphoxidation of Albendazole (ABZ) by rat intestinal microsomes
      has been examined. The results revealed intestinal sulphoxidation of ABZ by
      intestinal microsomes in a NADPH-dependent enzymatic system. The kinetic
      constants for sulphoxidase activity were Vmax = 46 pmol/min/mg protein and
      Michaelis constant Km = 6.8 microM. 2. The possible effect of inducers (Arochlor
      1254 and ABZ pretreatment) and inhibitors (erythromycin, methimazole, carbon
      monoxide and fenbendazole), was also studied. In rat pretreated with Arochlor
      1254, Vmax was 52 pmol/min/mg protein, whereas oral administration of ABZ
      increased the intestinal sulphoxidation of the drug, Vmax being 103 pmol/min/mg
      protein. 3. Erythromycin did not change the enzymatic bioconversion of ABZ, but
      methimazole and carbon monoxide inhibited the enzyme activity by approximately 60
      and 30% respectively. Fenbendazole (a structural analogue of ABZ) was a
      competitive inhibitor of the sulphoxidation process, characterized by a Ki or 69
      microM. 4. These data demonstrate that the intestinal enzymes contributing to the
      initial sulphoxidation of ABZ may be similar to the hepatic enzymes involved in
      the biotransformation process by the P450 and FMO systems, a conclusion that
      needs to be further established.

PMID- 7571718
TI  - N-hydroxylation and N-dealkylation by P4502C3 of N-methylbenzamidine: N
      oxygenation and N-oxidative dealkylation of one functional group.
AB  - 1. The first detection of a microsomal N-hydroxylation of an N-alkylated
      benzamidine possessing alpha-H atoms by P450 is now reported in the present in
      vitro biotransformation studies. 2. The newly found metabolites, N-hydroxy-N
      methylbenzamidine and N-methylbenzamidoxime, were identified after hplc
      separation by comparison of their retention times with those of synthetic
      reference compounds and by comixing methods. N-hydroxy-N-methylbenzamidine exists
      predominantly in the aminonitrone form and constitutes a novel type of
      metabolite. 3. By means of reconstitution experiments with purified P4502C3 from
      rabbit liver and with purified variants of 2C3 expressed in Escherichia coli, it
      has been shown that the N-hydroxylation and the N-dealkylation of N
      methylbenzamidine are catalysed by the same P450 isoenzyme. 4. A reaction
      mechanism is proposed in which the P450-dependent N-oxygenations and N
      dealkylation of N-methylbenzamidine are derived from a common intermediate. It is
      obvious that if alpha-H atoms are present N-dealkylation is observed; however, in
      contrast with previous concepts, N-oxygenation is also possible.

PMID- 7571720
TI  - Differential induction of rat hepatic microsomal and peroxisomal long-chain and
      nafenopin-CoA ligases by clofibric acid and di-(2-ethylhexyl)phthalate.
AB  - 1. Activity of rat hepatic microsomal and peroxisomal long-chain (palmitoyl) and
      nafenopin-CoA ligases were studied following administration of either clofibric
      acid, di-(2-ethylhexyl)phthalate (DEHP) or phenobarbitone. 2. Clofibric acid
      significantly induced the peroxisomal palmitoyl and nafenopin-CoA ligases, whilst
      no induction of the equivalent enzymes was observed in the microsomal fraction.
      3. DEHP induced only palmitoyl-CoA formation in peroxisomes, whilst all enzymes
      were refractory to phenobarbitone treatment. 4. The enzyme-specific patterns of
      inductions both intra- and inter-organelle suggest that the palmitoyl and
      nafenopin-CoA ligases are under different regulatory control. 5. Modulation of
      both the rate and extent of nafenopin- and palmitoyl-CoA formation was both agent
      and organelle specific. 6. This study highlights the difficulty in delineating
      the individual roles of both fatty acyl-CoAs and xenobiotic-CoAs in peroxisome
      proliferation.

PMID- 7571719
TI  - Induction of hepatic P450s in rat by essential wood and leaf oils.
AB  - 1. The effects of essential oils extracted from the wood and leaves of
      Chamaecyparis obtusa, Cryptomeria japonica and Thujopsis dolabrata on P450s in
      the hepatic microsomes of the male rat have been investigated. 2. Essential oils
      did not affect the content of total P450s measured photometrically. However, some
      metabolic activities and the levels of some forms of P450, including 2B1, were
      significantly increased, indicating their induction by essential oils. 3. The
      effects of components derived from essential oils (alpha-pinene, 1,8-cineole,
      cadinene and borneol) on P450s in rat hepatic microsomes were investigated. The
      activities of testosterone 2 beta-, 6 beta-, 16 alpha- and 16 beta-hydroxylation
      and the levels of P4502B1 and 3A2 were increased by 1,8-cineole and cadinene. The
      induction of P450s by essential oils is thought to be caused by cadinene, a major
      component. The P450 isoform induced by cadinene is similar to that induced by
      phenobarbital. However, the magnitude of induction by cadinene was less than that
      by phenobarbital at the dose levels studied. 4. P4502B1 and 3A2 were induced by
      essential oils in the perivenous area in the hepatic lobe.

PMID- 7571723
TI  - Identification of urinary metabolites of ecabapide in rat.
AB  - 1. 14C-Ecabapide, 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N-
      methyl[14C]benzamide, was dosed orally to rat (100 mg/kg). Within 48h after
      dosing, 36.7 +/- 5.4 and 55.7 +/- 11.8% of the administered radioactivity was
      recovered from urine and faeces respectively. 2. The unchanged drug was the major
      compound excreted in the urine and accounted for 37% of the urinary
      radioactivity. Seven urinary metabolites were purified by preparative hplc and
      their structures were elucidated by mass and 1H-nmr spectrometry. 3. The major
      metabolic pathway of ecabapide was found to be the formation of 3-amino-N
      methylbenzamide produced by N-dealkylation of the secondary amine at the 3
      position of the benzamide moiety followed by acetylation. 4. Further metabolic
      pathways of the N-methylbenzamide moiety were N-demethylation via the
      carbinolamine derivatives, and/or aromatic hydroxylation followed by
      glucuronidation.

PMID- 7571722
TI  - Selective effects of a bacterial infection (Actinobacillus pleuropneumoniae) on
      the hepatic clearances of caffeine, antipyrine, paracetamol, and indocyanine
      green in the pig.
AB  - 1. In order to investigate the effect of a bacterial acute phase response model
      on drug disposition in vivo, plasma clearances of antipyrine, caffeine,
      paracetamol and indocyanine green were investigated in the healthy and
      Actinobacillus pleuropneumoniae-infected pig. 2. Indocyanine green plasma and
      endogenous creatinine clearance were not changed during the infection, which
      indicates that hepatic blood flow and renal function were not significantly
      affected. 3. In the A. pleuropneumoniae-infected pig, plasma clearances of
      antipyrine and caffeine, both marker substrates for hepatic oxidative
      biotransformation, were decreased by 72 and 68% respectively. The clearance of
      paracetamol, a drug mainly glucuronidated in the pig, was reduced by 39%. 4. It
      is concluded that the most important change in drug elimination during an acute
      phase response induced by A. pleuropneumoniae is a suppression of oxidative
      hepatic biotransformation.

PMID- 7571721
TI  - Metabolic and pharmacokinetic studies following oral administration of
      famciclovir to the rat and dog.
AB  - 1. Drug-related material was well absorbed following oral administration of 14C
      famciclovir to the male rat at doses up to 4000 mg/kg and to the male dog at
      doses up to 250 mg/kg, as judged by the early onset of the peak blood or plasma
      concentrations of radioactivity (usually < or = 1.5h) and the rapid extensive
      excretion of radioactivity in the urine (57-76 and 86-89% of dose in rat and dog
      respectively). 2. Famciclovir underwent extensive first-pass metabolism in both
      species. In rat, following dosing at 40 mg/kg, famciclovir was rapidly and
      extensively metabolized to the active antiviral compound penciclovir, which
      reached peak concentrations in the plasma (mean 3.5 micrograms/ml) at 0.5 h. The
      6-deoxy precursor of penciclovir, BRL 42359, was the only other major metabolite
      detected in rat plasma. Cmax values for BRL 42359 (mean 2.2 micrograms/ml) were
      also achieved at 0.5 h. In dog, extensive conversion of famciclovir to
      penciclovir, via BRL 42359, also occurred, but its rate of formation from BRL
      42359 was somewhat slower than in rat. In dog, following dosing at 25 mg/kg, Cmax
      values for penciclovir (mean 4.4 micrograms/ml) occurred at 3 h and were lower
      than the Cmax values for BRL 42359 (mean 10.0 micrograms/ml) which were achieved
      at 1h. 3. A dose-dependent decrease in the conversion of BRL 42359 to penciclovir
      occurred in both species, resulting a changes in the ratios of the plasma
      concentrations of the two metabolites with increasing dose. In rat, the urinary
      excretion of penciclovir decreased from 36% of dose at 40 mg/kg to 21% at 4000
      mg/kg, and was accompanied by a corresponding increase in the urinary excretion
      of BRL 42359. In dog, a similar decrease in the urinary excretion of penciclovir
      occurred on increasing the dose of famciclovir from 25 to 250 mg/kg. 4.
      Penciclovir and BRL 42359 were the major metabolites detected in urine and
      faeces. In rat, following dosing at 40 mg/kg, 54 and 22% of dose were recovered
      in the excreta as penciclovir and BRL 42359 respectively. Corresponding
      recoveries of the two metabolites in the dog were 34 and 50% of dose. The
      metabolic fate of famciclovir in these animal species is, therefore, similar to
      that reported previously in man.

PMID- 7571724
TI  - Identification of ractopamine hydrochloride metabolites excreted in rat bile.
AB  - 1. Rats dosed orally with 2.85 +/- 0.30 mg [14C]ractopamine HC1 [(1R*, 3R*),
      (1R*, 3S*)-4-hydroxy-alpha-[[[3-(4-hydroxyphenyl)- 1-methylpropyl]-amino]
      methyl]([U-14C]benzenemethanol)hydrochloride] containing 1.44 +/- 0.15 microCi
      radioactivity excreted 58 +/- 7% of the administered radioactivity in the bile
      within 24 h. Absorption and excretion of radioactivity was rapid as 55% of the
      administered radiocarbon was excreted into the bile during the first 8-h
      collection period. 2. Radioactivity excreted in rat bile was partitioned by XAD-2
      column chromatography and reverse-phase hplc into at least seven different crude
      metabolite fractions; metabolites representing approximately 76% of the biliary
      radioactivity were isolated and identified from four of the crude metabolite
      fractions. 3. Approximately 46% of the biliary radioactivity was identified as a
      sulphate-ester, glucuronic acid diconjugate of ractopamine. Identification was
      based on 1H-nmr and negative-ion FAB-ms spectroscopy. Enzymatic and chemical
      hydrolysis of the sulphate-ester followed by co-chromatography of the hydrolysis
      products with synthetic ractopamine mono-glucuronides, established the site of
      sulphation at the C-10' phenol (phenol attached to carbinol) and glucuronidation
      at the C-10 phenol (phenol attached to methylpropyl amine) of ractopamine. 4. A
      metabolite representing approximately 6% of the biliary radioactivity was
      identified as a ractopamine mono-sulphate conjugate by using mass spectral and 1H
      nmr techniques. Sulphate was conjugated at the C-10' phenol of ractopamine and
      was not stereospecific. 5. Approximately 25% of the biliary radioactivity was
      identified as ractopamine mono-glucuronides. The major site of glucuronidation
      was at the C-10 phenol, but ractopamine glucuronidated at the C'-10 phenol was
      also present.

PMID- 7571725
TI  - Balance/excretion of 3H- and 14C-tyloxapol in the male rabbit after intratracheal
      administration.
AB  - 1. Tyloxapol, trace-labelled (50-100 microCi/animal) with 3H or 14C, was
      administered intratracheally in a surfactant formulation (EXOSURF Neonatal) to
      the male rabbit in a total tyloxapol dose of 5 mg/kg. Urine, faeces, expired air,
      and blood were collected for up to 10 days following tyloxapol administration. 2.
      Over 5 days, 3H-tyloxapol-related radioactivity in the urine (13.4%) and faeces
      (27.4%) accounted for a major fraction of the labelled dose. However, urine also
      contained an additional 13% of the dose as tritiated water. Expired air accounted
      for only 4.2% of the dose. At the end of the study, an additional 35.6% of the
      radioactive dose was found in tissues and the carcass, mainly in the lung (27.4%)
      and to a lesser extent in the liver (2.8%) and kidney (0.4%). Levels of
      radioactivity in other tissues, including whole blood, were low. 3. Over a
      separate 10-day study, faecal (30.4%) and renal (9.7%) elimination of 14C
      tyloxapol accounted for 40% of the radioactive dose, with expired air accounting
      for much less (2.7%). At the end of the study, additional radioactivity was
      recovered from the lung (43.9%) and to a lesser extent from the liver (3.8%) and
      kidney (0.3%). The half-life for the elimination of total radioactivity from the
      lung was estimated to be 10-12 days. 4. These data indicate that, following
      intratracheal administration, tyloxapol and metabolites were retained by the
      lung, released slowly into the systemic circulation, and eliminated through
      faecal and renal excretion.

PMID- 7571726
TI  - Covalent binding of suprofen to renal tissue of rat correlates with excretion of
      its acyl glucuronide.
AB  - 1. Dosing rat with suprofen produces suprofen equivalents that are covalently
      bound to plasma and tissue proteins in vivo. 2. Suprofen acyl glucuronide is
      reactive in vitro, resulting in suprofen equivalents covalently bound to proteins
      of plasma and tissues in a time-dependent manner. 3. Bile duct ligation of rat
      increases exposure to suprofen acyl glucuronide in vivo, which leads to enhanced
      covalent binding of suprofen equivalents to plasma proteins and to kidney tissue.
      4. Covalent binding of suprofen equivalents to kidney tissue correlates with
      excretion of suprofen and suprofen glucuronide by the kidney.

PMID- 7571727
TI  - [Specialty Symposium of the Federal Medical Office "Problem-Oriented Learning in
      Medical Education, Graduate and Continuing Education" 9 to 10 September 1994,
      Wurzburg].

PMID- 7571728
TI  - [Problem-oriented learning at the Gottingen University. Report of a 1 week
      introductory conference ("sample course")].
AB  - In Germany, a reform of the medical academic training is hotly discussed.
      However, only a few teachers and students can base their arguments on practical
      experience with new learning methods. Therefore, a one-week-try-out course
      ("Schnupperkurs Reformstudiengang") was organised at the university of Gottingen
      to gain experience in the problem-based learning. Tutorials took place according
      to the principle of the "seven steps" as practised in Maastricht. The students
      developed their own learning goals guided by a tutor. The acquiring of the
      subject was achieved by private studies, accompanying seminars, and practical
      training. An evaluation of the student's opinions on problem based learning and
      their satisfaction with the course was carried out by a questionnaire and group
      discussions. Our experiences show an open-mindedness of the academic staff and
      real enthusiasm on the part of the 21 participating students. Substantial for
      this success are--according to the results of the survey--the following items:
      The problem-orientated practical and interdisciplinary approach and teaching in
      small groups, which enabled a very close relationship between academic staff and
      students. A try-out-course might be a welcome entry to new forms of learning,
      because it offers practical experiences in new learning and teaching methods to
      open-minded lecturers and students. Therefore, such courses can contribute to an
      evolution at universities as they slowly but smoothly generate the essential
      competence needed to reform the medical education.

PMID- 7571729
TI  - ["Teachers' Training Course"--evaluation of continuing studies for faculty in the
      field of ethics in medicine].
AB  - The need for continuing education in the field of ethics in health professions is
      increasing. A project group of the Academy of Ethics in Medicine, Germany,
      developed and tested a model for a "Teachers' Training Course" to provide
      continuing education in this field. Evaluation data of the first two seminars are
      presented. These data demonstrate that the course matches the demands which
      participants have requested from such seminars.

PMID- 7571731
TI  - [Initial experiences with the new environmental medicine course in graduate
      education].
AB  - The "master of environmental medicine" is a new medical subspeciality in Germany.
      Specialised physicians can qualify for it, if they have spent at least an
      additional period of 1.5 years at a recognized institution in the field.
      Furthermore the attendance of a 200 hours comprehensive specialist's training
      course is required. Preliminary experience with this comprehensive course, as
      offered by our institution (Academy of Occupational and Environmental Medicine,
      Berlin, Germany) is lined out. Additionally, details of the curriculum, which was
      specifically designed for this purpose by our institution, are given. The results
      of an evaluation-procedure (questionnaire) among those participants, who
      completed the first parts of the course, are discussed.

PMID- 7571730
TI  - [The general practice course catalog--an attempt at quality assurance in graduate
      general practice education].
AB  - Additionally to the training in the hospital and in the practice, the rules for
      continuing education for general practise, established at the meeting of medical
      German physicians in 1992 demand the participation in theoretical seminars. The
      content and duration of these seminars is content and duration of these seminars
      is laid down in recommendations of the chamber of the physicians of Germany to
      ensure the quality of the courses. According to this, the first recommendations
      consists of the Course Book for General Medical Practise regarding a course of
      240 hours duration. This is a nation-wide standardized curriculum which was
      accepted from all German chambers of physicians as the basis of the further
      education in family medicine. The standardization and the structuring of the
      content, goals, and methods of teaching and learning as well as the organization
      of the seminars, the working materials for the teachers, regular training for the
      presenters and teachers, methods for a nation-wide evaluation of the seminars,
      and independence from commercial interests are the features to ensure the quality
      of the courses.

PMID- 7571732
TI  - [Experiences in organization of medical graduate and continuing education in the
      new German country (Thuringen)].
AB  - The switch from a state controlled to a self responsible continuing medical
      education could be completed in Thuringia within the first years after the
      reunification. Higher performances demonstrated by the just mentioned analyses
      can be observed quantitatively as well as qualitatively. This concept of our
      academy concerning a professional and regional decentralization in combination
      with centralized offers for further education has been proved. A good teamwork
      between the organizers and participants succeeds more and more in finding out the
      kind of teaching needed. Medical education can be planned globally and according
      to the needs. New ways of training can be searched and may go beyond country
      borders.

PMID- 7571733
TI  - [General practice continuing education--initial experiences with problem-based
      learning in a continuing education program].
AB  - In May 1994, the regional chamber of physicians of Westfalia/Lippe, Germany,
      introduced their qualifying course in family medicine with a new didactic
      approach: It changed from a more traditional lecture-based style to the emphasis
      of problem-based learning. The decision to do this was mainly driven by two
      reasons: firstly, the common experience of a declining attendance during regular
      whole day lectures and, secondly, the goal to implement regional quality-seminars
      following the course. In addition, the federal chamber of physicians published a
      guidebook with recommendations favoring a more problem-based approach to family
      medicine in order to implement changes. Although there is still much hesitance in
      Germany towards the implementation of problem-based learning, we think that this
      approach cannot only facilitate factual learning but also stimulates other
      important goals of medical education. Because of time restrictions, it was not
      possible to assess the outcome. However, participants valued their experience
      relatively high in a process-evaluation conducted during and after the course.

PMID- 7571734
TI  - [Does quality assurance modify clinical research, medical progress and medical
      graduate education in surgery?].
AB  - For years, external safeguard of quality has been continuously practised in the
      field of surgery by several local medical societies. Beside its original task of
      comparing and reviewing given standards of all surgical departments, other
      clinically or scientifically relevant questions can be answered on the basis of
      the enormous numerical data, too. The patient data, available to the chamber of
      physicians of Westphalia-Lippe, German, are showing that the experiences of
      clinical research rapidly and almost ubiquitously find their expression in the
      daily routine work of surgeons. Examples like the introduction of routine
      thrombosis prophylactics of changes in the surgical techniques for inguinal
      rupture and gallstone show how progress in medicine by postgraduate medical
      education is realized in the daily clinical workday routine.

PMID- 7571736
TI  - [5 years experience with resuscitation courses].
AB  - Examples for the effective teaching of core knowledge and skills of advanced life
      support courses are given. Didactive requirements of the skill stations for
      emergency treatment of cardiac arrest scenarios are discussed. A standardized
      course concept based on the recommendations of the American Heart Association
      (AHA) (1) and European Resuscitation Council (ERC) (2) as well as valid and
      mandatory certification and recertification procedures are deemed necessary for
      physicians active in emergency medical systems.

PMID- 7571737
TI  - [The "Patient Anxiety Seminar" as a graduate education program--effectiveness and
      use in general practice].
AB  - This article describes results of an evaluation study of a seminar for patients
      with anxiety, an education program for primary care physicians. Before and after
      the two seminars, 109 participants filled out a questionnaire about their opinion
      on the program as well as their attitudes, experience and knowledge in dealing
      with anxiety patients. They were compared with a control group which did not take
      part in the program. After 3 and 12 months, a part of the participants was
      interviewed again. It was found that anxiety patients call for a lot of attention
      from general practitioners and that diagnostic and therapeutic knowledge is not
      sufficient. The educational program was highly rated by the participants. The
      seminars were conducted in the practice by most of the participants in groups as
      well as on single patients. It became evident that in spite of high expenses
      there is a wide acceptance of such seminars and that the variables examined up to
      now indicate a surprisingly high efficiency of the educational programme.

PMID- 7571735
TI  - [Consensus as the basis of interdisciplinary graduate education curriculum].
AB  - Especially in the field of emergency medicine, it is necessary that medical
      standards are developed in general agreement with all faculty members. Standards
      should not only be understood as a basis for quality control but also as a
      helpful guide for the daily routine. The necessary agreement based on scientific
      discoveries and practical experiences, which find their expression in the general
      accepted knowledge of the specialty, has to be adapted to the special situation
      of emergency. Taking the head injury as an example, a special treatment schedule
      will be developed based on an interdisciplinary consent. The resulting training
      documents can than be offered to groups at different levels, since the content
      can be handled in a modular manner. The continuing education course will be
      available in a set of slides and provides an extensive overview of the topic
      "head injury" and supports the practical application with an algorithm.

PMID- 7571738
TI  - [The graduate education project in the new federal German lands "Diabetics-
      Management in General Practice"].
AB  - Supported by the federal ministry of health, the Central Research Institute for
      Ambulatory Health Care in Germany organised postgraduate courses with the topic
      "How to take care of diabetic patients" in cooperation with the society of panel
      physicians. Contents and media of the postgraduate course were developed with the
      help of experts, a formative evaluation of the curriculum was carried out. In a
      consensus- and preparatory meeting, diabetologists discussed the medical
      objectives with experts and were trained under the guidance of educationalists
      (microteaching with video-monitoring aiming at improving teaching behaviour).
      Later on, 1315 physicians participated in 38 postgraduate courses. The
      experiences of this project can provide useful informations how to structure
      postgraduate medical education.

PMID- 7571739
TI  - [Health promotion and nutrition counseling for obese patients--a responsibility
      of medical care].
AB  - For prevention and therapy of overweight the joined effort of physicians and
      nutritional consultants is suggested to be the most effective approach. To
      develop a model of cooperation, the present situation of communication has been
      analyzed by questioning 57 overweight volunteers (by questionnaire), 34
      physicians (both by questionnaire and interview), and 4 nutritional consultants
      (by interview). The physicians and the nutritional consultants feel the lack of
      communication and they express the wish to improve the cooperation. There is also
      a need for organizing structures of such collaboration, e.g. nutritional
      consultation either as part of the medical practice or as a special practice
      where the patient is to be referred to.

PMID- 7571740
TI  - [Graduate education in nutritional medicine in Germany--2 years after
      organization of the "Nutritional Medicine" teaching curriculum].
AB  - Prophylaxis of nutrition-related diseases and therapy of malnutrition are
      important duties of physicians. While teaching in nutrition for medical students
      is poor in German universities, progress has been made in regard to postgraduate
      training. Stimulated by the chamber of physicians of Germany, a "curriculum for
      Nutritional Medicine" was developed by the Germany Society of Nutritional
      Medicine. Experience gained by the Academy of Nutritional Medicine Hannover
      indicates that the postgraduate training based on this curriculum is well
      received. This may suggest that nutritional medicine is gaining greater
      acceptance.

PMID- 7571741
TI  - [Systematic aspects of problem-based, case-related, practice-oriented,
      professional continuing education].
AB  - Traditional CME using lectures has not been shown to improve patient care, which
      is the purpose of all learning in medicine. As knowledge taught mainly by
      lecturing is not useful for dealing with clinical problems, problem-based courses
      were developed to integrate general principles of basic and clinical sciences in
      undergraduate education. Case-based teaching is used for effective teaching of
      patient care. Six components were defined as a case system for clinical
      education: 1. Demonstration of patients; 2. free access to patients or data of
      patients, 3. responsible care of the patients, 4. acquisition of basic knowledge
      integrated in clinical problem-solving, 5. evaluation of documented work and 6.
      participation in patient related research. Surveys of general physicians showed
      that they regard a multitude of the components of the case system as desirable
      for learning in quality circles. Small group work can be implemented using
      computer supported work.

PMID- 7571742
TI  - [Case-oriented work in the quality circle].
AB  - Considering the discrepancy between scientific knowledge and definite behaviour
      during consultation ("performance gap"), acceptance, proceedings and case
      oriented work in quality circles/peer review groups are described. 79% of 138
      general practitioners declared that working in quality circles should base on
      cases from daily practice. Exchange of experiences and the expectation to get
      help for solving specific problems in the daily practice are the most important
      motives for participating in quality circles. For one circle as an example, the
      process of topic and case oriented work on the basis of objective documents from
      the practices of the participants and the following case oriented development of
      guidelines are described. Finally, the implicit chances of case oriented work in
      quality circles are shown with respect to existing experiences.

PMID- 7571743
TI  - [Implementation and evaluation of quality circles in general practice].
AB  - In the beginning of 1993, society of panel doctors Sudbaden, Germany, has
      constituted a group of experts from the Department of General Medicine of the
      university hospital and practising general practitioners (GPs) to develop an
      organisational and conceptional framework for setting up quality circles. At
      present, 23 quality circles with 6-12 participants are holding regular meetings
      every 4 to 8 weeks in the region of Sudbaden. The group members, who are all
      physicians working in primary health care, are selecting and discussion topics
      which are important in general practice. In order to facilitate the discussions,
      the research group has developed predefined guidelines covering a wide range of
      common and important conditions in general practice (Hypertension, sleeping
      disorders, diabetes mellitus, COPD, dementia, lower back pain, cardio-vascular
      disease, depression, headache, vertigo etc). In presenting these structurized
      guidelines, the moderator prompts and encourage the group members to identify
      common problems in their own practices. The use of these guidelines in, quality
      circles and research may provide a starting point for developing consensus
      guidelines. The quality circle projects is given as systematic evaluation for
      both participants and moderators at different levels. Main objectives of the
      assessment are the recruitment, motivation and the specific goals of general
      practitioners to participate in quality circles. Currently, we are evaluating the
      development of quality circle for a period of 18 months.

PMID- 7571744
TI  - [The pharmacotherapy circle--a promising way for improving quality in primary
      medical care].
AB  - Rational and efficient pharmacotherapy in a particular quality may be achieved by
      work in quality control seminars. During the last couple of years, seminars for
      pharmacotherapy have taken place at the Society of Panel Physicians of the German
      state Hessen under the supervision and scientific guidance of Lieselotte von
      Ferber, MD, University of Cologne. The kind of work in these seminars is
      demonstrated as well as the evaluated results. It can be proven that the quality
      of the pharmacotherapy is improved together with considerable savings in the
      costs of drugs without a decrease in the pharmaceutical care of the patients. The
      seminars for pharmacotherapy may be a suitable method to avoid legal actions for
      those physicians which may become liable of for compensation because of their
      high average of prescription costs.

PMID- 7571745
TI  - [Structured public health quality circle on the topic of diabetes management in
      general practice].
AB  - The efficacy of quality circles has not yet been evaluated in controlled studies
      in Germany. The Central Research Institute for Ambulatory Health Care in Germany
      conducted a prospective controlled trial in order to evaluate the effects of
      structured quality circles on the process of quality ambulatory care for diabetic
      patients. Following a training for moderators (two for each quality circle) two
      quality circles undertook five sessions. In a representative random sample (25
      diabetic patients per practice), the quality of diabetes care was evaluated
      before and after participation in the quality circles and was compared to the
      results of a control group without peer review. The participation in a quality
      circle resulted in a significant and relevant improvement of the quality
      concerning the detection of diabetes related complications.

PMID- 7571746
TI  - [Evaluation of a training program for moderators of panel doctor quality circles:
      a progress assessment].
AB  - We report about the first 7 seminars of a training programme for presenters of
      quality circles for panel doctors. The seminars aim to train techniques of
      moderating a group and to give a methodological background for the work with
      quality circles. 65 (44.2%) of the 147 participants were general practitioners,
      34 (23.1%) were internists and 32 (21.8%) were specialists of other disciplines.
      16 (10.9%) were not physicians or not working as a physician. An evaluation of
      the seminars by a structured questionnaire showed mean ratings of 2.1 for
      lectures [in terms of school-marks from 1 (very good) to 6 (very poor)] and 1.8
      for the work in small groups. Working atmosphere and opportunities for active
      participation were rated most positively. 6 months after the course, 64.9% of the
      participants already had arranged dates for meetings or had started with own
      quality circles.

PMID- 7571747
TI  - [Report of experiences with quality circles].

PMID- 7571749
TI  - [New kinds of 3-dimensional atlases of the anatomy and function of the human
      body].
AB  - It is a drawback of classical multimedia programs for the visualization of
      spatial knowledge, that they are based on a limited number of predefined views.
      This paper describes a model that combines pictorial and symbolic knowledge about
      spatial structures in a way that allows arbitrary views of the scene and the
      interrogation of the model in the context of the actual view. The style of the
      pictorial presentation only depends on the objective and the phantasy of the
      user. The functionality of the approach is demonstrated with the example of the
      human head. It is furthermore shown that the model potentially allows the
      simulation or generation of all classical visual teaching aids for anatomy.

PMID- 7571748
TI  - [Professional development of media in general practice].
AB  - In the German state Niedersachsen, the practical advantage of computers as an
      information medium in the out-patient care was tested in the medical practice for
      two years. In a two year study, acceptance, suitability, and the didactic quality
      of new information software for practice computers were investigated in 20
      medical practices. Under the supervision of the KVN, the support of a Multi
      Medica Corporation and IBM as well as numerous university departments, the
      multimedia software was prepared and further developed during the trial in the
      medical practice. It became clear, that videos, pictures, and text as short
      information units were helpful for the information of patients. The quick access
      and the simple and clear presentation is crucial for their usage. Teaching
      software for patients and multimedia programs for the continuing education of
      physicians have to be looked at separately. For this, longer information units
      might be necessary.

PMID- 7571750
TI  - ["Information versus Communication" Workshop].

PMID- 7571751
TI  - ["Knowledge versus action--quality circle work is different from traditional
      education" Workshop].

PMID- 7571752
TI  - ["The technique of problem-based learning--future of medical education
      curriculum?" Workshop].

PMID- 7571753
TI  - ["Use of interactive information technology in medical practice" Workshop].

PMID- 7571755
TI  - [Surgical therapy of uncomplicated ulcer: results of a prospective epidemiologic
      study. DUSUK Study Group].
AB  - In a prospective, multicenter and interdisciplinary study (DUSUK I) the present
      position of elective surgery in uncomplicated peptic duodenal and gastric ulcers
      was evaluated. Ten Dusseldorf hospitals (surgery and internal medicine)
      participated in the study. The investigation focussed on the proportion of
      operated patients related to hospitals and clinical disciplines, the operative
      procedure and results and possible selection criteria for the indication of
      operation. In the study period a total of 1030 patients with uncomplicated peptic
      ulcer was documented, an incidence of indoor patients with uncomplicated peptic
      ulcers of 180/100,000 inhabitants/year and an incidence of elective ulcer surgery
      of 7.5/100,000 inhabitants/year was calculated. Patients primarily admitted to
      surgical units were operated in 27% of cases (39/146) in contrast to 0.5% (4/884)
      of patients primarily admitted to internal units. The majority of hospitals
      perform rare or no elective peptic ulcer surgery at all. There is a considerable
      difference between the hospitals and clinical disciplines. The collective of
      operated patients concentrated on young patients with positive ulcer history. In
      the long run a negative effect on surgical training and results is apprehended.

PMID- 7571757
TI  - [Highly flexible self-expanding metal mesh stents: a new kind of palliative
      therapy of malignant dysphagia].
AB  - Metal mesh stents are a new way in the treatment of malignant stenoses. Between
      11/91 and 12/93 in 79 patients with malignant stenoses of the esophagus and the
      esophago-gastric junction 96 highly elastic, knitted, self-expanding nitinol
      stents (Ultraflex, Boston Scientific) were implanted. Most of the tumors being
      problematic, preoperated or preradiated, in 78 of 96 implantations endoscopic
      pretreatment (Laser, Argon Plasma Coagulation (APC), dilatation)--mostly in the
      same session--was necessary. Follow up time was 21 (2-108) weeks. In this pilot
      study 3.5 (1-27) controlendoscopies with 2.5 (1-10) endoscopic interventions were
      performed. 90 of 96 implantations were primarily successful and led to a
      functional success in 73 of 79 patients. The ability to swallow improved
      significantly, the score of dysphagia improved from 3.5 to 1.0 (p < 0.001). There
      were no relevant complications and no stent-related mortality. All stents could
      be kept patent during the follow up period using the new developed Argon-plasma
      coagulation (APC) to treat the ingrowth of granulation tissue or tumor, which was
      observed during follow up in 72 of 93 implantations. Tumor ingrowth represents
      the main problem of the method and demands endoscopic posttreatment (APC) in
      cases with relevant re-obstruction. Impairment of the stent lumen by tumor
      ingrowth (granulation tissue plays no role) would have been observed in about 60%
      of the patients without such a treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571756
TI  - Effect of human gastrin-17 with and without acid suppression on human esophageal
      motility.
AB  - The putative role of gastrin for the regulation of esophageal motility is a
      matter of debate. Accordingly it was the aim of this study a) to examine if
      physiological postprandial plasma levels of human gastrin-17 (hG-17) can affect
      esophageal motility, especially the pressure of the lower esophageal sphincter
      (LESP), and b) to assess the contribution of augmented acid secretion during
      gastrin infusion. In a first series of experiments postprandial plasma gastrin
      levels were determined in 8 healthy volunteers following the ingestion of a mixed
      meal. Gastrin rose from a baseline of 21 +/- 2 pg/ml to 67 +/- 8 pg/ml and
      returned almost to basal levels within 120 minutes. In a second experimental
      series the effect of i.v. synthetic human gastrin-17 (hG-17) was studied in 17
      volunteers. At a lower dose of 0.75 ng/kg/min hG-17 increased plasma gastrin to
      62 +/- 7 pg/ml while a higher dose of 1.5 ng/kg min elicited a supraphysiological
      increase to 119 +/- 11 pg/ml. Infusion of hG-17 caused a significant increase of
      the LESP from 19.0 to 25.8 mmHg (p < 0.05, low dose) and from 18.5 mmHg to 23.3
      mmHg (p < 0.05, high dose) when compared to the effect of i.v. saline. To exclude
      effects of augmented acid secretion during hG-17 infusion the experiments were
      repeated after complete blockade of acid secretion with famotidine 40 mg i.v.
      After famotidine pretreatment hG-17 caused a similar increase of LESP from 20.1
      to 25.9 mmHg (low dose) and from 19.9 to 24.1 mmHg (high dose).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571754
TI  - [Tell me, where the ulcers are, where have they gone?].

PMID- 7571758
TI  - [Liver cirrhosis in protoporphyria: bile acid therapy and liver transplantation].
AB  - Protoporphyria is an important differential diagnosis in patients with jaundice
      and cutaneous photosensitivity. In 1975 erythropoietic protoporphyria and liver
      damage of unknown origin were diagnosed in a 24 year old patient with
      photosensibility since early childhood. Laparoscopic liver biopsy confirmed
      protoporphyrin-associated liver cirrhosis in 1983. Therapy with ursodeoxycholic
      acid was initiated and liver function was stable during an 18 month period. In
      december 1989 the patient developed severe intrahepatic cholestasis with rapid
      deterioration of liver function. Liver transplantation was performed in 1990. The
      patient is now five years after transplantation in an excellent clinical
      condition. This 20 year observation period gives insight in the pathogenesis of
      protoporphyrin-induced hepatobiliary complications in a latent and overt phase.
      The relevant diagnostic and prognostic porphyrin parameters and therapy of
      protoporphyric liver disease are discussed.

PMID- 7571759
TI  - Acute abdominal pain in chronic pancreatitis: hemorrhage from a pseudoaneurysm?
AB  - An alcoholic, 67-year old retired male nurse complained of abdominal pain, loss
      of appetite and weight loss of 10 kg within one year. Based on elevated serum
      enzyme levels, ultrasonography and computed tomography examinations, an acute
      attack of chronic pancreatitis with several pancreatic pseudocysts was diagnosed.
      Ultrasonographically, an 1.8 cm phi, echo-free, pulsatile, space-occupying
      lesion, suggestive of a pancreatic pseudoaneurysm, was found at the right lateral
      margin of an almost echo-free pseudocyst measuring 6.8 x 5.6 x 5.0 cm in the head
      of the pancreas. Shortly before the planned discharge when the patient felt well,
      he developed acute abdominal pain. An immediate ultrasound examination showed an
      inhomogenous and echo-dense pseudocyst, in short, an acute hemorrhage. Rupture of
      the pseudoaneurysm of the Arteria gastroduodenalis was suspected and later
      confirmed by angiography and laparotomy. After proximal an distal ligation of the
      vessel and fibrin sealing of the inner surface of the cyst, the patient recovered
      and, under alcohol abstinence, has been free of symptoms since one year.

PMID- 7571760
TI  - [Hydrogen metabolism in the large intestine--physiology and clinical
      implications].
AB  - During the anaerobic metabolism of the colonic bacterial flora short chain fatty
      acids and the gases hydrogen (H2) and carbon dioxyde (CO2) are produced. In about
      50% of a European and North-American population and in 90% of rural black
      Africans, methane is generated from H2 and CO2. In methane-negative individuals,
      sulfate reducing bacteria utilize H2 to reduce sulfate to sulfide. Methanogenesis
      and sulfate reduction are usually mutually exclusive. A competition exists for
      the common substrate hydrogen which is potentially regulated by the availability
      of sulfate in the colonic lumen. Other bacteria can use H2 to reduce CO2 to
      acetate (homoacetogenesis). Methane is an inert gas and has probably no direct
      effect in man. The metabolites of sulfate reduction (mercaptides, hydrogen
      sulfide) are toxic and hydrogen sulfide is supposed to play a role in the
      pathogenesis of ulcerative colitis. All H2-utilizing metabolisms reduce the
      gaseous volume in the colon and thus prevent flatulence. In patients with
      pneumatosis cystoides intestinalis methanogenesis is absent and sulfate reduction
      is insignificant. This deficiency provides an explanation for the massive H2
      excretion in those patients and their symptoms.

PMID- 7571761
TI  - [Do immunosuppressive agents really impair glucose tolerance in liver transplant
      patients?].

PMID- 7571762
TI  - [Antibacterial treatment of gastric ulcers associated with Helicobacter pylori
      without acid suppression].

PMID- 7571763
TI  - [Nissle's late honorable recognition].

PMID- 7571764
TI  - [Modifying increased plasma cholesterol levels in secondary prevention of
      coronary heart disease].
AB  - In secondary prevention of coronary heart disease, the reduction of elevated
      cholesterol plasma levels is mainly based on diet and/or drugs. Invasive means
      such as partial ileal bypass operation or LDL-apheresis, although highly
      effective in reducing cholesterol levels and incidence of clinical cardiac
      events, should be reserved for special subgroups of patients. With dietary
      measures such as strict reduction of calories originating from fat, as well as
      with increased consumption of fish, fruits, vegetables and cereals, clinical or
      angiographic benefits could be demonstrated; in addition to the reduction of
      cholesterol plasma levels, other mechanisms such as inhibition of platelet
      aggregation and protection of LDL-particles from oxidation may contribute to this
      effect. With drugs reduction of cardiac events and of cardiac and total mortality
      was not observed in all clinical studies. Most angiographic drug studies revealed
      a significant, although quantitatively moderate retardation of the progression of
      coronary artery disease. However, only in a few studies did the clinical or
      angiographic effects correlate with the extent of changes in total, LDL- or HDL
      cholesterol plasma levels or their absolute values on trial. Women and men seem
      to benefit equally from drug therapy. The efficiency of cholesterol-lowering
      measures in patients with age > 70 years is still unknown, however. In patients
      with coronary artery disease and normal cholesterol plasma levels neither
      clinical nor angiographic benefits could so far be demonstrated with cholesterol
      lowering measures. Thus, to date in the secondary prevention of coronary artery
      disease cholesterol-lowering therapy with drugs only seems definitely indicated
      in patients < 70 years of age with hypercholesterolemia resistant to diet.

PMID- 7571767
TI  - [Single right coronary artery with absence of the left coronary ostium].
AB  - We report the rare congenital anomaly of a singular right coronary artery in
      absence of the left coronary ostium. In a 31-years-old man, coronary arterial
      angiography demonstrated a right coronary artery which, arising from the right
      Sinus Valsalvae, first described the normal right coronary arterial course but in
      the apical region continued to follow, in reverse direction, the normal course of
      the left anterior descending artery. The proximal diameter of the vessel measured
      5.2 mm. Thallium scintigraphy showed no ischemia of the anterior wall. The risk
      of developing circumscribed atherosclerosis due to anatomical reasons seems not
      to be increased, as no additional bifurcation nor kinking was to be found.

PMID- 7571766
TI  - Left ventricular hypercontractility in hypertensive patients with anginal pain
      and normal coronary angiograms.
AB  - This study was designed to assess left ventricular contractility in hypertensive
      patients with normal coronary angiography and anginal pain. An abnormally high
      percentage of hypertensive patients (approximately 30%) undergoing cardiac
      catheterization because of anginal pain and/or exercise-induced ST-segment
      depressions has angiographically normal coronary arteries. Possible reasons for
      these signs of ischemia include a microvasculopathy, metabolic abnormalities and
      an increased oxygen consumption as a result of left ventricular
      hypercontractility which was studied here. Left ventricular volumes and ejection
      fraction were determined in 50 patients with arterial hypertension (23 men, 27
      women, age 60 +/- 8 years, RR 154 +/- 24/91 +/- 12 mm Hg) by cardiac
      catheterization and computerized analysis of laevocardiographies. The control
      group were 50 normotensives (30 men, 20 women, age 57 +/- 12 years, RR 128 +/-
      12/76 +/- 8 mm Hg) without coronary artery disease. The angiographical data were
      correlated with age, sex. ECG, echocardiography, laboratory findings, medication
      and duration of hypertension. The left ventricular ejection fraction was
      significantly increased in the group of hypertensives (75.8 +/- 6.3 vs. 67.7 +/-
      5.0%, p < 0.001). This difference was mainly due to a significantly reduced
      endsystolic left ventricular volume (37.1 +/- 15.3 vs. 47.7 +/- 10.8 ml, p <
      0.001); enddiastolic left ventricular volume was not significantly different
      (140.5 +/- 26.8 vs. 149.0 +/- 27.5 ml, p > 0.1). A hyposystolic form of
      hypertensive heart disease was not observed in this group of patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571768
TI  - [Single left coronary artery after orthotopic heart transplantation: angiography
      and intravascular ultrasound findings].
AB  - A 23-year-old man underwent orthotopic heart transplantation due to dilative
      cardiomyopathy, receiving the heart of a 32-year-old donor. Coronary angiography
      7 weeks following transplantation revealed a single left coronary artery arising
      from the left coronary sinus, and as a coronary abnormality the right coronary
      artery was originating from the proximal left anterior descending branch.
      Angiographically the single coronary artery showed no stenoses or irregularities.
      Intravascular ultrasound examination (30 MHz, 3.5-F catheter) demonstrated
      relevant atherosclerotic lesions along the stem, the proximal and middle portion
      of the left anterior descending artery, and especially at the origin of the
      equivalent of the right coronary artery. Thallium-201 stress testing showed only
      discrete filling defects at the inferior wall. After orthotopic heart
      transplantation intravascular ultrasound investigation can, in addition to
      angiography, become extremely relevant especially in heart recipients with a
      single left coronary artery because vessel wall alterations of the stem and left
      anterior descending artery may influence the prognosis of these recipients.

PMID- 7571765
TI  - [Temporal trends in myocardial infarct morbidity, mortality and 28-day fatalities
      and medical management. Results of the Augsburg Myocardial Infarct Register 1985
      to 1992].
AB  - Between 1985 and 1992 a significant decrease in rates of acute myocardial
      infarction (AMI; fatal and non fatal, including prehospital cardiac death) from
      533 cases per 100,000 population of 455 cases was observed in the 25- to 74-year
      old male study population (linear regression model: -13%, p < 0.01). In the
      corresponding female study population the AMI rate increased from 153 cases per
      100,000 population in 1985 to 153 cases in 1992 (linear regression model: +18%, p
      < 0.05). The decrease was only in 50- to 59-year-old male AMI patients without
      changes in risk factors (smoking, diabetes, hypertension, recurrent AMI) but with
      a decrease in patients with a history of angina pectoris, which may have been
      caused by intensified medical treatment of AMI endangered patients. Over time 34%
      of the patients died before hospitalization and another 19% died within the first
      24 h after hospitalization. The register results show an underestimation of the
      coronary mortality by the official cause of death statistics. In contrast, the
      significant increase in treatment with thrombolytics (men from 16% to 38%, women
      from 8% to 42%), beta-blockers (men from 48% to 69%, women from 45% to 71%), and
      antiplatelets (men from 55% to 94%, women from 52% to 91%) was not related to any
      significant changes in 28-day case fatality of the 24-h survivors (men and women
      13% to 14%). Without media campaigns, for the increased number of cases
      hospitalized within 4 h after the event (1985-1987 men 50%, women 42%; 1990-1992
      58% and 60%; p < 0.01) thrombolytic treatment shows an increase from 25% in men
      and 17% in women (1985-1987) to 54% in men and 47% in women (1990-1992; p <
      0.01).

PMID- 7571769
TI  - [Stress echocardiography--a new test for evaluating the anti-ischemic effect of
      medication].
AB  - Exercise echocardiography and exercise electrocardiography were performed to test
      the anti-ischemic effects of isosorbide dinitrates (2 x 40 mg) und nisoldipine (2
      x 10 mg) using a randomized, double-blind, placebo-controlled crossover trial. A
      total of 24 patients with symptomatic coronary artery disease and exercise
      induced ST segment depression underwent 144 investigations (6 in each patient) at
      the first placebo treatment, 1st and 8th day during treatment with the first drug
      and the second placebo treatment 1st and 8th day during treatment with the second
      drug. A wall motion score (sum of 14 segments; wall motion grading: normal = 1,
      hypokinetic = 2, akinetic = 3, dyskinetic = 4) and ST depression at the exercise
      were used to assess the anti-ischemic effects. Both drugs reduced the number of
      exercise-induced wall motion abnormalities on the maximal comparable exercise
      level in comparison to placebo treatment. The wall motion score on the maximal
      comparable exercise level during placebo treatment was 25.5 +/- 6.9, during
      isosorbide dinitrate treatment (1 day) 23.5 +/- 7.2 and 23 +/- 6.7 (8th day; for
      both treatment days, p < or = 0.001 vs. placebo treatment), and during
      nisoldipine treatment (1st day) 23.6 +/- 5.9 and 23 +/- 6.8 (8th day; p < or =
      0.001). ST segment depression changed at exercise during first placebo treatment
      to 0.153 +/- 0.068 mV, during ISDN treatment to 0.102 +/- 0.055 (1st day, p <
      0.001) and to 0.117 +/- 0.056 (8th day, p < 0.001). ST segment depression during
      nisoldipine treatment was 0.121 +/- 0.075 mV on the 1st day (p < or = 0.002) and
      0.120 +/- 0.071 mV on the 8th day (p < 0.001). Exercise echocardiography can be
      used to test anti-ischemic drug effects. There were no differences in the
      reduction of exercise-induced ischemia between the two drugs.

PMID- 7571771
TI  - [A rare form of heart metastasis: hypernephroma. Successful surgical treatment].
AB  - An unusual cardiac metastasis, occurring in a 63-year-old man 19 years after
      nephrectomy because of renal cell carcinoma, is reported. The tumor extended from
      the right ventricle apex to the mid-portion of the interventricular septum. A
      complete excision could be achieved. To our knowledge, this is the third case of
      a renal cell carcinoma metastasis to the right ventricle which could be detected
      during a patient's lifetime and treated surgically. A review of the literature is
      also reported.

PMID- 7571770
TI  - [3-dimensional reconstruction of multiplanar transesophageal echocardiography
      images: a methodologic report with case examples].
AB  - First experience with the dynamic three-dimensional reconstruction of
      transesophageal echocardiographic images in more than 100 patients with various
      cardiac diseases are reported. Ninety different two-dimensional image planes were
      acquired for each reconstruction using a conventional multiplanar transducer,
      connected to a stepper motor and controlled by a computer-based image acquisition
      system with special software. Acquisition time for one data set was 2.3 +/- 0.9
      min, and calculation time to achieve three-dimensional images was 20-45 min.
      Several cardiac structures were reconstructed and analyzed qualitatively and
      quantitatively (measurements of distances and areas, volume calculation by
      Simpson's rule). Image sequences showing three-dimensional depth by gray scale
      modification were generated. After image acquisition one can select any desired
      cut plane to achieve perspectives that cannot be obtained by two-dimensional
      technique. Advantages of three-dimensional echocardiography are the display and
      potential quantification of pathomorphology of the left ventricle and mitral
      valve, atrial septal defects, intracardiac masses (i.e., myxomas, vegetations),
      and direct spatial imaging of complex congenital heart diseases. In principle,
      three-dimensional data sets have advantages for the quantitative evaluation of
      irregular formed cardiac structures, since the three-dimensional data set is more
      complete than cross-sections used in conventional two-dimensional
      echocardiography. Currently, however, these advantages are limited by the
      necessity of human interaction to segment the structures of interest.

PMID- 7571772
TI  - [Seminar on management in interventional coronary angioplasty and high-frequency
      ablative therapy. Wuppertal, June 10-11, 1994. Proceedings].

PMID- 7571773
TI  - Angioplasty or thrombolysis for acute infarction?
AB  - The benefit of thrombolytic therapy for acute myocardial infarction has been
      conclusively established by many trials. Direct angioplasty (without thrombolytic
      therapy) is often utilized urgently for patients with acute infarction based on
      observational studies. Recently, three randomized trials compared outcomes of
      patients undergoing thrombolysis versus direct angioplasty. The results of these
      trials indicate that either strategy, if applied early, can benefit patients with
      acute infarction. Specific advantages of angioplasty include slightly higher
      patency and flow rates in the infarct-related artery. However, thrombolysis is
      more readily available to large segments of the population. Either therapy must
      be applied early to be effective.

PMID- 7571774
TI  - [High frequency current catheter ablation in treatment of supraventricular and
      atrioventricular tachycardia].
AB  - Radiofrequency catheter ablation has been established as a first line therapy for
      the curative treatment of patients with atrioventricular nodal reentrant
      tachycardia and atrioventricular tachycardia encompassing accessory pathways as
      well as for ablation of the "normal" AV-junction. For these indications, the
      success rates exceed 90%. Acute complications during ablation of accessory
      pathway and ablation of the "normal" AV-junction occur in approximately 2-5% of
      patients treated. The incidence of complications during modification of the
      atrioventricular node to cure AV-nodal reentrant tachycardias clearly depends on
      the ablation technique used. The anterior approach with ablation of the so-called
      "fast pathway" carries a significantly higher risk of complete AV-block when
      compared to the inferior approach (so-called "slow pathway ablation")
      (approximately 4-8% vs. 2%). Arrhythmia recurrence after successful ablation of
      the "normal" AV-junction occurs only rarely, while the recurrence rate after
      modification of the AV-node or ablation of accessory pathway is approximately 10%
      during long-term follow-up. Recently, it has been shown that other, rare types of
      supraventricular tachycardia (sinus-atrial reentrant tachycardia, ectopic atrial
      tachycardia, human type I atrial flutter) can also be successfully ablated using
      radiofrequency current. In addition, first clinical results indicate that
      modification of anterograde AV-nodal conduction properties in patients with
      atrial fibrillation and fast ventricular rate by radiofrequency application to
      postero- and midseptal sites might be a useful therapeutic tool to slow
      ventricular rate. Because of the high success-rate and the relative low incidence
      of severe procedure related complications, the indications of radiofrequency
      ablation procedures for the treatment of supraventricular tachycardias will be
      extended in the future. In addition, it might be reasonable to expect that during
      the next years, all types of supraventricular tachycardia, except atrial
      fibrillation, can be targeted and cured by radiofrequency ablation in the
      majority of cases.

PMID- 7571775
TI  - Automatic implantable cardioverter-defibrillator: history and future
      developments.
AB  - The clinical experience with automatic internal defibrillation is now extensive,
      with over 65,000 patients treated since the first implantation in 1980. The
      success of the technique is largely the result of the perseverance and foresight
      of Dr. Michel Mirowski, although many people were eventually involved. The author
      was privileged to participate almost from the very inception of the project. The
      early experiments and some of the difficulties along the way leading up to the
      present extensive favorable human experience are described.

PMID- 7571776
TI  - [Automated implantable cardioverter/defibrillators. Indications for implantation
      and clinical results].
AB  - Since the first implantation in 1980 about 55,000 automatic
      Cardioverter/Defibrillators (ICD) were implanted worldwide. This paper overviews
      the development of indications for ICD implantation as well as clinical results
      especially with respect to prophylaxis of sudden cardiac death.

PMID- 7571777
TI  - [Successful high frequency current catheter ablation of an accessory conduction
      pathway in the "neck region" of a coronary sinus aneurysm. A case report].
AB  - In this case report the electrophysiological findings in a 24 year old female
      patient are demonstrated. For about 12 years she suffered from recurrent
      atrioventricular reentrant tachycardia with a rate of 230 beats per minute.
      Electrophysiological study resulted in diagnosis of a posteroseptal accessory
      pathway. Ablation was attempted primarily from a left ventricular access, but the
      pathway could not be reached from this position. After contrasting the coronary
      sinus a large coronary sinus aneurysm could be diagnosed. The accessory pathway
      was located in the "neck"-region of the aneurysm. By application of
      radiofrequency current in this location the bypass tract could be ablated. This
      case report shows that accessory pathways in coronary sinus aneurysms can be
      ablated without complications in this location.

PMID- 7571778
TI  - [Ventricular bigeminy with fixed with fixed coupling at rest and during exercise
      as the cause of recurrent dizziness and syncope--successful anti-arrhythmic
      therapy by high frequency current catheter ablation of a right ventricular
      arrhythmogenic focus. A case report].
AB  - In a 52-year-old patient with beginning dilatative cardiomyopathy dizziness and
      syncopes could be observed due to a ventricular bigeminy at rest and under
      exercise conditions. The patient also showed a marked reduction of exercise
      capacity and was handicapped in his profession as electrician and unable to work
      for more than 10 months. Antiarrhythmic drug therapy including the subsequent use
      of all available antiarrhythmic agents failed in suppressing this arrhythmia. In
      an electrophysiological study the arrhythmogenic focus could be localized in the
      right ventricular outflow tract. Application of radiofrequency current resulted
      in instantaneous termination of the extrasystoly; this result could be documented
      in repeat Holter monitorings over 12 weeks to present. This case report shows
      that radiofrequency catheter ablation can in special cases be applied for therapy
      of extrasystolic phenomena when clinical symptoms necessitate treatment and
      antiarrhythmic drug therapy fails.

PMID- 7571779
TI  - [Electrophysiologic findings and high frequency catheter ablation in
      atriofascicular and nodoventricular pathways ("Mahaim bundles")].
AB  - So-called "Mahaim-pathways" represent a distinct subset of accessory pathways and
      the preexcitation syndromes with unique electrophysiologic properties. During
      sinus rhythm, preexcitation is minimal or absent whereas incremental atrial
      stimulation reveals preexcitation with a left bundle branch block like
      morphology. "Mahaim-fibers" exhibit long conduction times, decremental conduction
      properties by atrial extrastimuli or incremental atrial pacing, and conduction
      only in the anterograde direction. The typical atrioventricular reentrant
      tachycardia incorporating a "Mahaim-pathway" is a preexcited antidromic
      tachycardia with anterograde conduction over the accessory pathway and retrograde
      conduction over the AV node. "Mahaim-fibers" may be associated with dual AV node
      physiology or common atrioventricular accessory pathways. The original concept of
      "Mahaim-fibers" consisted of accessory pathways originating in the AV node and
      inserting into the distal right bundle branch ("nodofascicular" pathways) or the
      right ventricle ("nodoventricular" pathways). This understanding has been
      challenged by surgical interventions identifying the atrial insertion of "Mahaim
      pathways" at the parietal tricuspid annulus. Later, electrophysiologic and
      surgical studies have confirmed the antero-to posterolateral atrial origin of
      these accessory pathways remote from the atrioventricular node. Therefore, the
      concept of nodoventricular pathways has been replaced by the concept of
      atriofascicular pathways. Recently, endocardial catheter mapping and
      radiofrequency catheter ablation have substantially contributed to the
      characterization of this unusual form of the preexcitation syndrome. Distinct,
      high-frequency activation potentials of atriofascicular accessory pathways can be
      recorded at the atrial insertion at the antero- to posterolateral tricuspid
      annulus and along the entire ventricular course up to the ventricular insertion
      in the right ventricular apical region near or at the distal right bundle branch.
      The long conduction times and the decremental conduction properties result from a
      delay in the interval from the local atrial activation at the atrial insertion to
      the activation potential of the accessory pathway whereas the conduction time
      between the activation potential of the accessory pathway and the local
      activation at the ventricular insertion is relatively constant. Overall, the
      current knowledge about atriofascicular pathways is indicative of a proximal AV
      node-like component and a distal bundle-branch-like component and, therefore,
      suggestive of an accessory AV conduction system. Radiofrequency current
      application for ablation of atriofascicular pathways can be accomplished at their
      atrial insertion and along their entire ventricular course. Highfrequency
      activation potentials of the atriofascicular pathways identify target sites for
      ablation. Transient mechanical conduction block by catheter manipulation at the
      subannular level of the atrial insertion has also been introduced as a marker for
      successful ablation of these unusual accessory pathways.

PMID- 7571780
TI  - [Treatment of ventricular tachycardia with bypass surgery. A case report].
AB  - We report on a 45-year-old man with a 4-year-old myocardial infarction and a
      history of recurrent syncopes. A monomorphic ventricular tachycardia was
      inducible during electrophysiologic study. After coronary bypass-grafting
      ventricular tachycardia was no longer inducible. The patient is now, 6 months
      after surgery, and without antiarrhythmic drugs, free from recurrence of syncope
      and has had no spontaneous tachycardia event. Treatment with antiarrhythmic
      drugs, endocardial resection, and the implantable cardioverter-defibrillator are
      well established approaches to fight sudden cardiac death. The role of coronary
      artery bypass-grafting alone in the prevention or suppression of malignant
      ventricular arrhythmias is debatable, especially in cases of monomorphic
      ventricular tachycardia. Some of these high-risk patients may well be protected
      by coronary artery bypass grafting alone.

PMID- 7571781
TI  - Cardiogenic shock in acute myocardial infarction. Improving survival rates by
      primary coronary angioplasty.
AB  - This study reports on 16 patients suffering from cardiogenic shock in the setting
      of acute myocardial infarction (11 men, five women; average age: 52.5 +/- 14
      years) treated by means of primary coronary angioplasty: These 16 patients were
      part of a total population of 261 patients suffering from acute myocardial
      infarction at the time of admittance to the Wuppertal Heart Center, who were
      consecutively treated during the period from 1/90 to 6/94 by primary coronary
      angioplasty without having received any prior thrombolytic therapy. For all
      patients, primary re-opening of the vessel infarcted was successful. The period
      of time between onset of pain until re-opening of the vessel averaged 176 +/- 49
      min. Eleven patients suffered from multi-vessel coronary artery disease. Prior to
      re-opening, systolic blood pressures averaged 66 +/- 10 mm Hg; average biplan
      left ventricular ejection fraction, 40 +/- 12%; left ventricular end-diastolic
      pressures (LVEDP), 26 +/- 7 mm Hg. In 63% of the cases evaluated, it proved
      possible to document collaterals to the infarcted vessel. Thirteen patients
      survived acute coronary occlusion. Two patients died due to protracted myocardial
      pumping failure, despite re-opened arteries that effectively re-established
      coronary flows. Showing symptoms of re-occlusion, one patient developed
      electromechanical decoupling. Thirteen patients were discharged from the hospital
      for normal life or subsequent treatment. Overall, this corresponds to an in
      hospital survival rate of 81%. During follow-up examinations performed over 14 +/
      8 months (range 3 to 30 months), all of the patients are alive. Mean left
      ventricular ejection fraction increased to 56% +/- 17%; mean left ventricular end
      diastolic pressure dropped to 14 mm Hg +/- 5 mm Hg. In the infarct-related artery
      there was no recurrence of stenoses exceeding 50%. By now, one of the patients
      has received elective aorto-coronary bypass grafting; for another one, multi
      vessel PTCA of non-infarcted arteries is being employed; 77% of the patients
      state that they are satisfied with the quality of their lives. These results
      demonstrate that rapid revascularization using coronary angioplasty in
      cardiogenic shock following acute myocardial infarction substantially improves
      the prognosis for survival and favorably influences long-term outcome. Thus,
      primary PTCA is the method of choice for treating cardiogenic shock; any patient
      and particularly those resistant to lyse therapy-should immediately receive this
      treatment.

PMID- 7571782
TI  - [PTCA or alternative techniques? Balloon angioplasty remains dominant].
AB  - The use of second generation devices like excimer laser, rotablator, directional
      atherectomy, and stents is increasing. It is noteworthy that they are used in
      most cases in combination with "balloon" dilatation. The application of these
      more expensive techniques requires more experience and skills than mere balloon
      dilatation. Today, however, only three randomized trials were able to document
      some advantage of alternative devices in comparison to the traditional lumen
      enlargement with balloons (BENESTENT, STRESS, ERBAC). The following paper
      reflects our experience with balloon angioplasty in more than 15,000 patients, as
      well a critical review of new devices that were used in 19% of our patients in
      1993.

PMID- 7571783
TI  - Primary mechanical recanalization of occluded coronary arteries without prior
      thrombolytic therapy in patients with acute myocardial infarction. A single
      center study reporting acute results and complications.
AB  - This study reports on 261 consecutive patients admitted to the Wuppertal Heart
      Center with acute myocardial infarction (186 men, 75 women; average age: 58.2 +/-
      11.6 years) and then treated by primary coronary artery angioplasty. Sixteen
      patients with cardiogenic shock were included, as well as 42 patients aged > or =
      70 years, 51 patients with contraindications for thrombolysis, and 13 patients
      with prior coronary bypass surgery. All patients were treated between 12/89 to
      6/94 and had not received prior thrombolytic therapy. The period of time between
      onset of pain and revascularization of the infarct-related vessel averaged 224 +/
      205 min. Half of the patients had multi-vessel disease, and about 31% had had a
      prior myocardial infarction. 100 patients suffered from an anterior wall
      infarction, 109 patients from an inferior wall infarction, 50 patients from a
      posterolateral infarction, and in two cases the infarct localization could not be
      determined from the ECG. Mean biplane left ventricular ejection fraction averaged
      56 +/- 13%, left ventricular end-diastolic pressure 20 +/- 7 mm Hg. In about 50%
      of the patients collaterals to the infarct-related coronary artery could be
      documented. With the first contrast injection into the infarct-related vessel
      TIMI flow 0/I was demonstrated in 94.9%, TIMI flow II in 5.7% and TIMI flow III
      in 0.4%. Reopening of the infarct-related coronary artery with establishment of
      TIMI-flow III was primarily successful in 91.9%. Average time for coronary
      angiography and angioplasty in the cathlab was 69 +/- 28 min. In 29 patients an
      autoperfusion balloon catheter was used to treat manifest or threatening
      reocclusion. Thirty-day-mortality in the total study group was 3.4%. In patients
      aged > or = 70 years mortality raised to 14.3%; in patients in cardiogenic shock
      mortality increased to 18.7%, in patients with inferior wall infarction up to
      5.5%, and in cases with multi-vessel disease up to 5.0%. The in-hospital and 30
      day course were complicated by major peripheral bleeding in seven patients (2.7%)
      requiring blood transfusions and surgical femoral vascular repair, and in another
      two patients with a false aneurysm which was treated by surgical means. No
      hemorrhagic stroke occurred, but three ischemic strokes with complete restitutio
      ad integrum within the 30-day-observation period were registered. As major
      cardiac complication early re-occlusion of the initially reopened infarct-related
      coronary artery was diagnosed in 10 patients; 11 patients developed a re
      infarction within the first 30-days, in three cases leading to a fatal
      outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571785
TI  - Coronary stents.
AB  - As early as 1912, endovascular support devices were tried in canine aortas to
      maintain luminal patency in various conditions. Stents were introduced into
      clinical practice in 1986 to treat abrupt closure and to prevent restenosis after
      angioplasty. In 1994, two major randomised trials have confirmed that stenting
      after PTCA does indeed reduce the incidence of restenosis as well as other events
      such as myocardial infarction and emergency surgery. Numerous different stents
      are now in use: self expanding and balloon expandable stents, stainless steel
      stents and tantalum stents, flexible and articulated stents, and more recently
      heparin-coated stents. All stents are foreign bodies and may induce spasm and
      thrombosis. Meticulous drug treatment helps to reduce the side-effects of stents.
      New designs with improved fluid dynamics and optimal conformability are now being
      successfully tested. Polymer stents have not fulfilled their expectations.
      Optimal implantation strategy-aiming at an absolutely perfect primary result with
      no residual narrowing, absence of dissections and complete stent expansion--has
      dramatically reduced the complication rate after stenting as well as the need for
      heavy anti-coagulation. Stents have revolutionised the practice of transluminal
      techniques and hold great promise as local drug delivery devices.

PMID- 7571784
TI  - [Alternative methods in interventional therapy of coronary heart disease].
AB  - Percutaneous high-frequency coronary rotablation using the rotablator is able to
      remove arteriosclerotic material from the vessel wall. A diamond-coated (30-80
      microns) brass burr drill fastened to a flexible drive shaft rotating and
      tracking along a drill coaxial guide wire is used. The turbine rotates the drive
      shaft in excess of 150,000-190,000 rpm. High-frequency rotational angioplasty was
      successful in > 90% of patients, but in about 90% additional PTCA is necessary.
      No increase of bypass surgery compared to PTCA is observed. CK and CR-MB
      elevation is more often found than after PTCA. Vessel perforation is rarely
      observed. All vessels were open at 24-h control. The restenosis rate seems not be
      increased. The main indications for high-frequency rotational angioplasty are
      rigid and calcified sclerotic lesions which cannot be passed by conventional
      balloon catheters. Whether the restenosis rate can be reduced by this method will
      be judged in part by the COBRA study. In order to avoid acute complications of
      PTCA and to reduce restenosis rate, coronary stents were developed. Self
      expandable and balloon expandable stents are available. It could be demonstrated
      that these stents can be used as a bail-out system and can block elastic recoil
      of coronary arteries. The major remaining problem is subacute closure of coronary
      vessels. In order to prevent thrombosis treatment with coumarine, acetylsalicylic
      acid, and dipyridamol is necessary. Coronary stents can be successfully delivered
      in more than 90% of the patients. In a highly selected patient group using single
      stents restenosis rate could be significantly reduced.

PMID- 7571786
TI  - The autoperfusion balloon catheter with special attention to its use as a bail
      out device.
AB  - The most serious complication of coronary angioplasty is acute vessel closure
      and/or persistent major dissection. In these cases the autoperfusion balloon is
      probably a good solution to "tack" the dissection flap against the vessel wall
      and to establish flow with prolonged inflations. In this short overview we review
      the literature and give guidelines for the use of autoperfusion balloon catheters
      as a bail-out device.

PMID- 7571787
TI  - [High frequency current catheter ablation in ventricular tachycardia].
AB  - Since its introduction into clinical practice in 1982, catheter ablation has
      evolved as a first-line mode of non-pharmacological therapy in patients with
      atrioventricular nodal reentrant tachycardia and in patients with
      atrioventricular tachycardia involving an accessory pathway. The initial
      experience was based on the use of direct current for ablative purposes. However,
      since severe complications have been observed using this energy source,
      radiofrequency (RF) current catheter ablation is now the most frequently used
      technique. Efficacy rates are high (> 80%) in patients with idiopathic
      ventricular tachycardia and bundle-branch reentrant tachycardia. In addition, the
      technique also has a relatively high acute success-rate in patients with
      incessant ventricular tachycardia. However, RF current catheter ablation is less
      effective in patients with drug-resistant, chronic, sustained ventricular
      tachycardia after myocardial infarction or in the presence of dilated
      cardiomyopathy. Further improvements which include new criteria for the
      localization of the origin of ventricular tachycardia as well as technical
      improvements are particularly needed in this subgroup of patients. Thus, RF
      current catheter ablation in patients with ventricular tachycardia can be
      considered a promising new mode of non-pharmacological therapy. The efficacy rate
      of the procedure is highly dependent on the presence and type of organic heart
      disease as well as the mechanisms underlying ventricular tachycardia. Due to the
      limited experience, especially with respect to the long-term results, RF current
      catheter ablation is still an experimental mode of antiarrhythmic treatment.

PMID- 7571789
TI  - [Gigantic arm lymphedema].
AB  - It is told the course of a disease of a 44-year old woman who got a gigantic
      lymphedema of the arm within 5 years after a treatment caused by breast cancer 10
      years ago. There are described the psychical and social consequences and there
      are also analyzed reasons how such an extreme lymphedema of the arm could be
      possible. An incessant success of the treatment could only be achieved by a
      combination of plastic operation to reduce the tissue and consistent use of
      physical therapy of edema according to Asdonk, a combination of manual lymph
      drainage therapy according to Vodder-Asdonk and compression treatment.

PMID- 7571788
TI  - [Lipedema].
AB  - The "Lipedema" or "Fatedema" is conditioned by a slight mechanical obstruction of
      the small lymphatic vessels by the increasing pressure of the growing fat tissue.
      This lymphostasis in a normal lymphatic vessel system arises only with women and
      always symmetrically and conducts to typical complaints. Therapeutically, apart
      from loss in weight, only lymph drainage therapy is in a position to remove the
      complaints of edema.

PMID- 7571790
TI  - [Effectiveness, indications and contraindications of manual lymph drainage
      therapy in painful edema].

PMID- 7571791
TI  - [Seaside Zechlin/Brandenburg Clinic. First lymphology specialty clinical in new
      unified Germany].

PMID- 7571792
TI  - [Is treatment of lymphedema an interdisciplinary treatment?].

PMID- 7571793
TI  - A comparative clinical trial of graduated compression stockings and O-(beta
      hydroxyethyl)-rutosides (HR) in the treatment of patients with chronic venous
      insufficiency.
AB  - As overall conclusions from this study, and the two preceding comparable trials
      in which TcPO2 was measured in patients with (8) and without (7) stockings, we
      propose that: All patients with symptoms and oedema of CVI should be advised to
      wear suitable compressive stockings (this study); if they do wear stockings, then
      additional benefit may be derived from treatment with HR (8); for patients who
      are reluctant to wear stockings, for a variety of reasons, or in whom stockings
      may be contraindicated (e.g. mixed arterio-venous disease), then HR is an
      acceptable alternative (7 and this study).

PMID- 7571794
TI  - [Comparative histomorphometry of subchondral bone density and articular cartilage
      thickness in the tibial head in early human arthritis].
AB  - The articular cartilage thickness and subchondral bone density of 50 human tibial
      heads were histomorphometrically measured by an image analysing system and
      topographically examined in relation to age, sex and grade of osteoarthrosis
      (OA). Altogether we evaluated 12,000 items. Independent of OA the lateral tibial
      plateau shows a significant thicker cartilage layer than the medial. In central
      joint areas we find a thicker cartilage cover than in marginal. Corresponding to
      the literature cartilage fibrillation according to OA grade 1 and 2 (Otte 1969,
      Fassbender 1975) accumulates in the lateral and dorsal tibial head including the
      meniscus covered area. The cartilage thickness decreases with age independent of
      OA. Without major alterations of the topographical pattern the cartilage
      thickness however shows a significant increase in early OA (grade 1). For that
      reason measurements of the cartilage thickness and joint space narrowing are not
      appropriate for defining early OA. The subchondral bone density shows high values
      ventromedially and dorsolaterally independent of sex, age or OA. Beneath central
      joint areas higher values are found than marginally. Corresponding to the topical
      literature our results point at the model of the real loaded knee joint, which
      says that the mean loading forces do not act on the middle of the joint but on
      the medial plateau. The dorsolateral density centre could be an expression of the
      functional adaptation of the bended knee joint. In joint areas with cartilage
      fibrillation (OA grade 1) we find a significant higher subchondral bone density
      without major alterations of the topographical pattern. It is not possible to
      define cause and effect, we interpret both as result of higher joint loading.

PMID- 7571796
TI  - [Isokinetic muscle training with high motion speeds in the rehabilitation
      following surgical treatment of fresh anterior cruciate rupture].
AB  - In the course of a prospective investigation 17 patients with operatively treated
      acute anterior cruciate ligament ruptures received an isokinetic muscle training
      with high motion velocities in addition to the common physiotherapy from the 7th
      to the 19th week after operation. The comparative group consisted of 17 patients
      with operatively treated acute anterior cruciate ligament ruptures who were
      receiving the common physiotherapy only. The aim of the study was to improve both
      the postoperative dysbalance between agonists and antagonists and the active
      muscular stabilisation of the knee. The isokinetic muscle training was done with
      150 degrees/s and a motion limit for flexion/extension of 0-20-90 degrees. The
      postoperative muscular dysbalance was improved significantly in the isokinetic
      group after 6 weeks of training compared to the control group. The
      flexion/extension ratio of the operated leg at 60 degrees/s came to 100% in the
      training group compared to 135% in the control group. This difference was even
      more apparent at 180 degrees/s with 100% in the isokinetic group compared to 160%
      in the control group and at 240 degrees/s with 110% compared to 200%
      respectively. The average maximum torque was 10 to 15% better with the training
      group as with the control group though there was no training of maximum force
      done explicitly. There was no effect on the postoperative anterior stability of
      the knee.

PMID- 7571795
TI  - [Primary hypertrophic osteoarthropathy].
AB  - A case of the very rare primary-hypertrophic-osteoarthropathy (Touraine-Solente
      Gole-Syndrome) is reported. A middle-aged women was suffering from chronic joint-
      and limb-pain for more than twenty years. All diagnostical experiences only
      showed a cortical thickening mainly of the tubular bones and a craniosclerosis
      but no link for the possible origin. As typical for the disease, periosteal
      reactions could be discovered in X-ray examinations too. Thickening of the facial
      skin as well as drumstick-configurations of the fingers could be seen. A
      pulmonary affection leading to a secondary pulmonary osteoarthropathy (Pierre
      Marie-Bamberger's Syndrome) could be excluded. The syndrome presented here is
      only to be found in 3 to 5% of all cases with hypertrophic osteoarthropathy. It
      is a rare differential-diagnosis of chronic bone and joint pain.

PMID- 7571797
TI  - [Intraosseous pressure measurement in Kienboeck's disease--initial findings].
AB  - Intraosseous pressure was measured under standardized and different functional
      conditions in 11 necrotic lunates in different stages of the disease and in 11
      viable lunates. Both the viable and the necrotic lunates show a significant
      increase of the pressure, if the wrist is brought into dorsiflexion. Both groups
      do not differ significantly, but the mean value of the necrotic group exceeds
      that of the viable group clearly. There might have some technical problems in
      measuring. Venous stasis by tourniquet provoked increase of pressure, too. The
      increase of pressure both in dorsiflexion and in venous stasis is evidence of
      venous drainage. Dorsiflexion impairs the venous drainage of the lunate, which
      promotes necrosis. The increase of intraosseous pressure in necrotic lunates can
      be understood as a failure of the physiologic regulation of the intraosseous
      pressure by moving the wrist and cause of necrotic changes.

PMID- 7571798
TI  - [Significance of the radial compression syndrome for the diagnosis and surgical
      therapy of so-called epicondylitis humeri radialis (Epic. hum. rad.)].
AB  - 25 patients with Tennis Elbow were examined after surgery (= retrospectively), 25
      before surgery (= prospectively). All of the patients were operated on according
      to the Wilhelm and Wachsmuth method. 5-18 months after surgery (on average 10),
      both groups underwent clinical examinations. Those patients who still had
      symptoms were given neurophysiological examinations. Both groups were compared
      with each other. The following results were obtained from the comparison: 1) 7
      patients (28%) in the retrospective group were dissatisfied with the results of
      surgery and still had symptoms specific to the disease. In the prospective group,
      only 2 patients (8%) complained of similar problems. 2) 6 of the above-mentioned
      7 dissatisfied patients in the retrospective group agreed to a postoperative
      neurophysiological examination. This revealed in five out of six patients damage
      to the radialis nerve. 3) At the clinical examinations of the 25 prospective
      patients, 17 were suspected of having radial compression syndrome. In 9 patients,
      this suspicion was confirmed by the neurophysiological findings. A neurolysis of
      the N. radialis was performed on these nine patients during surgery. All of these
      patients were satisfied with the results of surgery at the follow-up examination.
      The above results permit the following conclusions: 1) The failures in surgical
      treatment of Tennis Elbow can in part be put down to radial compression syndrome.
      2) A thorough clinical examination, which in particular takes radial compression
      syndrome into account, should be carried out on every Tennis-Elbow-patient. 3)
      The neurophysiological examination of the main extensors of the hand should be an
      obligatory part of pre-operative preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571799
TI  - [Elbow contracture caused by increased tonus of the flexor muscles].
AB  - Increased muscle tone leads occasionally to fixed flexion and supination
      deformities of the elbow in tetraplegics and subsequently to additional
      restriction of function. The incidence, course, remaining functions and
      therapeutic measures were studied retrospectively in 22 patients (37 arms).
      Muscle hypertonus was found to start during the first 12 weeks after spinal cord
      lesion and to provoke a flexion contracture of 35 to 95 degrees in 40% of the
      cases despite therapy. Due to the failure of physical therapy and operative
      measures, prophylaxis through the prevention of shoulder-pain, early use of
      adequate splinting of the upper extremity and electrical stimulation of the
      triceps brachii should be carried out.

PMID- 7571801
TI  - [Osteochondromatosis in shoulder joint arthrosis--a case report].
AB  - We report on a 59 year old patient with repetitive shoulder trauma due to
      numerous grand mal convulsions and consequent severe osteoarthritis of the
      shoulder joint with formation of multiple loose bodies. We discuss the aetiology
      of the loose bodies as being different to those found in synovial chondromatosis,
      as well as the radiological, histological, clinical and therapeutical features of
      this entity.

PMID- 7571802
TI  - [A case of an old posterior shoulder luxation].
AB  - Posterior dislocation of the shoulder is rare. Only 2-3% of dislocated shoulders
      are displaced posteriorly. It is a diagnostic trap for young doctors. Over 60% of
      the cases are not diagnosed initially. This is a case report of a patient treated
      with physical therapy and even mobilisation in anesthesia for 2 years and then
      needed a total shoulder replacement.

PMID- 7571800
TI  - [Total elbow arthroplasty in the salvage of pseudarthrosis of a supracondylar
      humerus fracture].
AB  - Non-union of a supracondylar fracture of the humerus in the elderly leads mostly
      to profound disability because of great instability and pain. When osteosynthesis
      is not possible from a technical point of view, total arthroplasty can be a very
      satisfying solution.

PMID- 7571803
TI  - [Form and structure of the metatarsal head arch in adults. Ultrasonographic and
      podometric studies].
AB  - Ultrasonic measurements (n = 172) and plantar pressure investigations (n = 119)
      are performed on the forefeet of healthy adults, in order to constitute a
      correlation between shape and function of the anterior metatarsal arch. The
      thickness of the sole of the foot has its maximum beneath the 2nd metatarsal head
      and its minimum beneath the 1st and 5th ray. The highest pressure values are
      found at the 2nd and 3rd metatarsal head. It is concluded that despite the arch
      like configuration of the forefoot there is no structural arch function. The
      biological principle of adequate padding of pressure points results-depending on
      the load-in a different thickness of the soft tissues of the sole of the foot.
      The higher pressure under the central metatarsal heads is accompanied by thicker
      soft tissue pads and a more dorsal position of these rays.

PMID- 7571804
TI  - [Analysis of pressure distribution for the evaluation of gait in patients with
      hallux valgus surgery].
AB  - Peak pressures and regional impulses were determined under the feet of 58
      patients treated by a Keller/Brandes surgery. The values were taken in walking by
      means of a capacitance pressure distribution platform and compared to the
      pressure values of a normal collective (n = 111). 95% of the patients were
      satisfied with the surgery. A shift of the pressure and the regional impulse from
      the hallux to the metatarsal heads, especially to the III. metatarsus could be
      found.

PMID- 7571805
TI  - [Proprioceptive deficit following cruciate lesions--afferent disorder or
      compensatory mechanism?].
AB  - It was suggested that the ACL has not only mechanical functions but also acts as
      proprioceptive organ. In cruciate deficient knees pathological patterns of muscle
      control were found. These findings could be caused by a disturbed afferent signal
      from the disrupted ACL or by secondary changes in muscle innervation, which shall
      protect the instable knee against subluxation. 33 patients with unilateral
      operative ACL repair (21 cases with primary suture, 12 cases with autogenous
      ligamentum-patellae-reconstruction; average post op 36.5 yr) were examined
      clinically and with the KT 1000 arthrometer (MEDMETRIC Inc.). Patients history
      was evaluated by using the LYSHOLM score. During a cycling task the
      electromyographic activity was monitored from the thigh muscles (M. vastus lat.
      and med., lat. and med. hamstrings). In comparison to the ACL deficient patients,
      we tested 25 healthy subjects of same age and activity level. In the ACL group
      the following differences to the normals were found: the M. vastus lat. showed a
      significantly delayed onset, earlier end and shorter duration. M. vastus med. had
      the same pattern; the delayed begin of activity and the shorter duration were
      statistically significant. M. biceps femoris showed a significant later onset and
      shorter duration. So did the medial hamstrings; the differences, however, were
      not statistically significant. There was no significant difference between
      operated and healthy leg in the ACL group. By comparing the primary sutures and
      the ligamentum-patellae-reconstructions no significant differences were found.
      The instable patients (KT 1000 > 3 mm) of the ACL group showed more distinct
      differences in the EMG pattern than the patients with stable knee
      joints.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571806
TI  - [Idiopathic varus gonarthrosis: diminished nociceptive vs. unchanged
      somatosensory sensitivity].
AB  - Neuromuscular control deficits are supposed to contribute to the development of
      osteoarthritis (OA). Pain measurements were performed to clarify whether
      nociceptive afferents differ between OA patients and healthy subjects. Thermal
      pain thresholds were significantly higher in OA subjects as compared to controls,
      but there was no difference in perceptual thresholds after electrical
      stimulation. Lateralization, gender, site of OA changes, previous operations, or
      medication did not affect these findings.

PMID- 7571807
TI  - [Biomechanics of the hip joint in children].
AB  - Based on the data derived from the examination of 16 infantile and juvenile
      anatomical hip specimens as well as the radiological examination of 1350 hip
      joints of healthy children, a biomechanical model of the developing hip was
      computed. This two-dimensional vector model describes the forces acting on the
      growth plates of the head and the greater trochanter during the one-legged
      stance. It could be proven that the apophysis of the greater trochanter is
      subject to compressive stress by lateral-cranial traction bands and therefore
      corresponds with a "pressure apophysis". The muscle forces acting on the
      trochanter apophysis can be combined as a trochanteric resultant RT. This
      stimulates a lateral-cranial growth of the trochanter apophysis. The direction of
      the hip abductors and, as a result, also the direction and the length of Pauwels'
      hip resultant R are influenced by this mechanism.

PMID- 7571808
TI  - [Cause of pain in early dysplasia coxarthrosis. A case report].
AB  - The case of a 48 year old woman with a synovial cyst of the hip joint and
      arthrosis secondary to dysplasia is presented Rheumatic disease could be
      excluded. During an arthrography, which showed the communication of the cyst with
      the hip joint, the formerly existing pain could be elicited. In this case the
      pain in beginning hip dysplasia is not directly related to arthrosis.

PMID- 7571809
TI  - [Developmental tendency of the femur head following femoral head necrosis due to
      conservative treatment of a dislocated hip (2nd report)].
AB  - The development of the proximal femur was studied in a follow up of 64 patients-
      on average 24.4 years of age--with congenital hip dislocation and 101 subsequent
      aseptic necroses of the femoral head. For measurement of the angle of antetorsion
      and the femoral neck-shaft angle, biplanar radiographs were taken. A coxa valga
      with a true femoral neck-shaft of 137 to 164 degrees was present in one third of
      the cases with partial necrosis and in the group without necrosis. An increasing
      degree of necrosis led to coxa vara. Damage of the capital epiphysis caused
      development of coxa vara (average of 115.77 degrees), overgrowth of the greater
      trochanter and increase of femoral antetorsion (average of 30.23 degrees). Pre
      existing damage of the capital epiphysis following non-operative treatment of
      congenital hip disease or Perthes disease cannot be recommended for
      intertrochanteric varisation osteotomy.

PMID- 7571810
TI  - [Results of cementless acetabular revision surgery].
AB  - The great number of hip revision arthroplasties and the cementless fixation of
      arthroplasties has led to more and cementless hip revision operations with bone
      transplantation. This retrospective study shows the results of a clinical and
      radiological follow-up of 34 patients with an average age of 71 years and 4
      months at their hip revision arthroplasty. The subjective and clinical result in
      the Harris-Hip-Score 3 years and 9 months (1 year 4 months-6 years 3 months)
      after surgery shows 67% of the patients content with the result of the revision
      arthroplasty. The Harris-Hip-Score shows an average of 41.1 points preoperatively
      and 73.2 points at the follow-up examination. The loosening-rate was 11.8%, all
      arthroplasties which seemed loosened radiologically had also a bad result
      clinically. No correlation could be shown between the age of the patients and the
      clinical results as well as between an additional stem revision (15 patients) and
      the clinical result in the Harris-Hip-Score. All revision operations were done
      with bone transplantation and demonstrate, that the concept of cementless
      fixation of acetabular component gives satisfactory results.

PMID- 7571812
TI  - [Theses of papers presented at the 3rd (XVI) meeting of the Physiologic Society
      of the Russian Academy of Sciences].

PMID- 7571811
TI  - [Allograft transplantation in pelvic instability following prosthesis exchange].
AB  - The collective consists of 19 patients with 21 operations after multiple revision
      operations with complete pelvic instability. The reconstruction was done with
      tibia (11x) and femur allografts (6x). The bridging was reached by pressfit
      contact. The junction side was supplemented with autologous bone chips. The
      allografts were fixed with screws or plates. In all patients a good primary
      stability was achieved. Partial weight bearing was gained within 10.1 week and
      full weight bearing in 15.1 weeks. We notice one allograft fracture after 4
      months and one infection after 3 months. The reoperation rate was 4. The clinical
      results are encouraging. No lytic lines were seen between the acetabulum cup
      implant and the allograft within 20.1 months time.

PMID- 7571813
TI  - Workshop group: Australia, Ireland, North America, Scandinavia and UK.

PMID- 7571814
TI  - Workshop group: Central and Eastern Europe.

PMID- 7571815
TI  - Call for action/proposal of resolutions.

PMID- 7571816
TI  - Interactive session. III: Passing of resolutions.

PMID- 7571817
TI  - The European Public Health Association.
AB  - The European Public Health Association (EUPHA) was founded in 1992 and represents
      11 European countries. Its goals include encouraging collaboration in furthering
      European public health through research, education and action based on sound
      scientific grounds. It provides an opportunity for those interested in public
      health to meet and exchange information, both through an annual conference and a
      quarterly scientific journal. EUPHA is delighted to be represented on the Viral
      Hepatitis Prevention Board and supports the aims of the Congress.

PMID- 7571818
TI  - Interactive session. I.

PMID- 7571819
TI  - Introduction to epidemiology and risk of hepatitis B.
AB  - The most important modes of transmission of hepatitis B virus (HBV) are sexual,
      needle stick (both accidental or through intravenous drug use), blood transfusion
      or from mothers to newborns. The outcome of HBV infection mainly depends on the
      immune response of the host but is also influenced by the capability of the virus
      to escape defence mechanisms by integration into the genome of the host's
      hepatocytes. These factors affect whether HBV infection leads to acute hepatitis
      or remains asymptomatic, whether the infection resolves to immunity or becomes
      chronic and whether chronic clinical sequellae such as chronic hepatitis, liver
      cirrhosis or hepatocellular carcinoma develop. The epidemiological status of a
      given country with regard to HBV depends on socioeconomic factors, the proportion
      of individuals with risky life styles, the pre-existing prevalence of HBV, the
      vaccine programme available and compliance to hygienic measures.

PMID- 7571822
TI  - Incidence and prevalence of hepatitis B in France.
AB  - Reporting of hepatitis B is not compulsory in France, but it is estimated that
      8500-9000 acute cases and 100,000 hepatitis B infections occur every year.
      Seroprevalence studies have been carried out in selected populations. Every blood
      donation is screened for HBsAg, alanine aminotransferase elevation and anti-HBc
      antibody. Prevalence of HBsAg has declined from 13.9 positive donations in 1986
      per 10,000 to 5.3 in 1991. In pregnant women, overall seroprevalence is estimated
      at 0.8-1%, which represents more than 5000 children born each year to carrier
      mothers. Screening of HBsAg for all women when six months pregnant is now
      compulsory. Heterosexual patients at STD clinics were shown to have a very high
      risk of being infected with hepatitis B virus, with a chronic carrier rate of 4
      5%. In hospital employees before the introduction of vaccination, the overall
      incidence of hepatitis B was 100-300 acute cases per 100,000 employees per year.
      Risk varied according to exposure to blood; the highest incidence was found in
      nurses in dialysis wards. Vaccination against hepatitis B is now compulsory for
      all hospital and laboratory workers and medical and paramedical students. In
      preventive medicine consultants, routine medical check-up showed an overall HBV
      prevalence of 2.2% and a carrier rate of 0.3% in men and 0.1% in women.
      Immunization of all newborns and adolescents has recently been adopted in France,
      vaccination at school of adolescents aged 10-11 years being the main target.

PMID- 7571821
TI  - Overview of epidemiology and disease burden of hepatitis B in the European
      region.
AB  - The European Regional Office of the World Health Organization (WHO) carried out a
      survey to collect the available surveillance data on hepatitis B and to determine
      the preventive strategies and policies in 50 countries in the European region. A
      questionnaire was sent to every country to obtain data on acute hepatitis B
      incidence over the past five years as well as estimates of the prevalence of
      hepatitis B carriage and infection in the general population. Although the
      surveillance systems vary in their methods and completeness, the pattern of
      disease is clear. In western Europe, rates vary from north to south. Southern
      countries have incidence rates of about 6 per 100,000 per year whereas northern
      countries such as Scandinavia, Ireland and the UK have much lower rates of about
      1 per 100,000. Central Europe has markedly higher rates of about 20 per 100,000
      per year. The highest rates are found in the Central Asian Republics, where the
      rates are close to 100 per 100,000 per year. Mortality data on cancer liver
      diseases are also available. These, together with data on the prevalence of
      hepatitis B in the general population of each country, provide estimates of the
      number of deaths attributable to hepatitis B for each country. These estimates,
      in comparison with other preventable causes of death, illustrate the importance
      of hepatitis B in Europe. Most countries have some form of selective vaccination
      policy, although the risk groups targeted vary markedly from country to country.
      Only Albania, Bulgaria, France, Israel, Italy, Portugal and Spain have
      implemented national universal hepatitis B vaccination programmes.

PMID- 7571820
TI  - Epidemiology of hepatitis B infection in North America.
AB  - Although the USA is considered an area of 'low' endemicity for hepatitis B
      infection, the incidence of new cases, the prevalence of carriers, and the burden
      of acute and chronic disease place hepatitis B among the most important
      communicable diseases. It is estimated that 300,000 new cases of hepatitis B
      infection occur each year. These acute infections lead to 350-450 fulminant
      deaths, 27,000-42,000 chronic carriers and ultimately 4000-5500 deaths per year
      from cirrhosis and primary liver cancer. Most reported cases occur among young
      adults, many of whom belong to 'high risk' groups defined by lifestyle or
      occupation. In 1991, sexual transmission was the predominant mode of transmission
      (41% of cases by heterosexual activity; 14% by homosexual activity); percutaneous
      drug use was also important (12% of cases). Infection in healthcare workers
      represented only 2% of reported cases, and is the only group where falling
      incidence is due to vaccine use. However, 26% of cases occur in people who deny
      belonging to any 'high risk group'. Public health officials in the USA concluded
      that the 'high risk group' immunization strategy would not lead to the control of
      hepatitis B infection on a population basis. In 1992, it was recommended that all
      newborns in the USA receive hepatitis B vaccine as part of their routine
      immunization schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571824
TI  - Risk of hepatitis B in adolescence and young adulthood.
AB  - In countries of low hepatitis B virus (HBV) endemicity, infection occurs mainly
      in adolescents and young adults (15-34 years old). The most important risk
      factors for infection are heterosexual activity, homosexual activity and
      intravenous drug use. In industrialized countries, therefore, HBV infection is
      classified among the major sexually transmitted infections, as more than 50% of
      infections are spread in this way. Transmission from mother to newborn and during
      infancy is of less importance, except in some countries of southern Europe and in
      some southern states of the USA. The highest concentrations of HBV are found in
      blood of infected individuals, but HBsAg is also present in semen and vaginal and
      cervical secretions, which forms the biological explanation for sexual
      transmission of the virus. In epidemiological studies, HBV is, in general,
      associated with indicators of sexual activity such as number of lifetime or
      recent sexual partners, years of sexual activity and a history or serological
      marker of other sexually transmitted infections. Providing immunity from
      infection before risk-taking behaviour is adopted should be the major control
      strategy for HBV infection. Just as for other sexually transmitted infections,
      this can be best achieved by universal vaccination of young adolescents or
      infants, or both groups.

PMID- 7571823
TI  - Epidemiology of viral hepatitis B in Italy.
AB  - Hepatitis B has been one of the major public health problems in Italy in the last
      30 years. This is shown by the number of carriers of hepatitis B virus (HBV)
      among the population (approximately 1.5 million) and the large number of deaths
      (approximately 9000) in Italy each year ascribable to liver disease as a result
      of previous HBV infection (chronic hepatitis, cirrhosis, primary liver cancer).
      In the last 20 years the incidence of hepatitis B has gradually decreased due to
      demographic and socioeconomic changes which have occurred in Italy and to the
      preventive measures adopted. The major result so far obtained is the marked
      reduction in new infections and therefore in the prevalence of HBsAg carriers in
      infancy and childhood (aged < 14 years). In older age groups, both the prevalence
      of HBsAg carriers and the annual rate of new cases of acute hepatitis B are still
      above the average for northern Europe. In particular, the highest incidence of
      new hepatitis B cases (approximately 10 in 100,000) currently occurs in subjects
      between 15 and 24 years of age. For these reasons, the health authorities decided
      to combine general measures aimed at preventing the transmission of HBV infection
      with a programme of universal, compulsory, vaccination of adolescents at 12 years
      of age and of newborns. The aim of the present strategy, which started in the
      second half of 1991, is to drastically reduce the rate of HBV infections within
      the next 12 years.

PMID- 7571825
TI  - Risk of hepatitis B in infancy and childhood.
AB  - Hepatitis B virus (HBV) may be transmitted from mother to child during delivery
      or in the neonatal period (vertical transmission) or by direct person to person
      contact in teenagers and adults (horizontal transmission). Patients infected
      horizontally, as occurs in countries with a low prevalence of infection, achieve
      complete resolution in up to 95% of cases and acquire permanent immunity. On the
      other hand, 95% of infected newborns cannot clear the virus and remain chronic
      carriers. The relevance of this method of infection in newborns is twofold.
      First, because of persistent infection throughout life, they are at risk of
      developing liver cirrhosis and hepatocellular carcinoma. Second, they are
      permanent reservoirs of hepatitis B infection, facilitating its spread. Even in
      countries with low or intermediate prevalence, the importance of vertical
      transmission is manifest. In a study carried out in our hospital before screening
      of pregnant women for hepatitis B surface antigen (HBsAg) was implemented, the
      prevalence of HBsAg carriers among 8200 pregnant women was 1.24%, 6% of whom were
      HBeAg positive, for a minimum rate of transmission of HBV of 6%. From these data,
      there will be at least 65 children per year in Catalonia who become chronic
      carriers and about 1000 children at risk of acquiring HBV infection.
      Epidemiological studies carried out in Catalonia confirmed our results. Among
      children under 10 years of age in whom vertical transmission was likely, 1.7% had
      serum markers of HBV infection and 0.2% were HBsAg positive. These data confirm
      the need for universal HBV prevention in newborns, in addition to any other
      programme carried out in teenagers or adults.

PMID- 7571826
TI  - The proceedings of of an international congress on hepatitis B: the story of an
      unfinished business.

PMID- 7571828
TI  - Selective risk group strategies in North America.
AB  - Policies for hepatitis B immunization in Canada and the USA evolved from 1982 and
      culminated in recommendations for universal vaccination in both countries in
      1991. In policies developed between 1982 and 1985 there were clear national
      recommendations for the immunization of selected risk groups, e.g. healthcare
      workers, recipients of multiple blood products, infants of HBsAg-positive mothers
      and those at high risk for sexual transmission. By 1988, both countries had
      policies for prenatal screening. It is evident that most vaccine was delivered to
      healthcare workers and that the epidemiology of the disease did not change as a
      result of selective strategies. However it is very important, for the foreseeable
      future, to continue selective immunization programmes in addition to a universal
      strategy in order to protect those presently at risk.

PMID- 7571827
TI  - Introduction to current control of hepatitis B as a community health risk.
AB  - Vaccines against hepatitis B have been shown to be protective and can control the
      disease much more effectively than hygienic measures. When vaccination failure is
      reported, it is the strategy that has failed--not the vaccine.

PMID- 7571829
TI  - Selective risk group strategies in Europe.
AB  - Most countries in northern and western Europe belong to areas with a low
      endemicity of hepatitis B virus (HBV). When HBV vaccines became available, these
      countries adopted a vaccination strategy that targeted groups at high risk of
      hepatitis B. However, it became obvious that this strategy, despite giving good
      protection to those who had been vaccinated, had largely failed. This was firstly
      because, with few exceptions (e.g. haemodialysis patients and haemophiliacs),
      only medical and dental workers were vaccinated in any great numbers, whereas
      only a few individuals in other risk groups were reached. Second, it was found
      that less than half of all hepatitis B cases occurred in individuals in typical
      high-risk groups. In Germany, for example, about three-quarters of all infections
      occur in people who would never be reached by the high-risk vaccination strategy,
      most of these individuals having been infected by heterosexual contact. Thus a
      universal vaccination strategy has to be implemented to control the spread of
      hepatitis B in the population and to eventually eliminate the disease.

PMID- 7571830
TI  - Global programme for control of hepatitis B infection.
AB  - The hepatitis B virus (HBV) has infected more than 2000 million persons alive
      today and 350 million persons are chronically infected carriers of the virus, at
      high risk of death from active hepatitis, cirrhosis and primary hepatocellular
      cancer. Each year approximately 1 million people die from the acute and chronic
      sequelae of HBV infection, making it one of the major causes of morbidity and
      mortality in man. In May 1992, the World Health Assembly, the governing body of
      the World Health Organization, endorsed recommendations stating that countries
      with an HBV carrier prevalence of 8% or more should have hepatitis B vaccine
      integrated into their national immunization programmes by 1995 and that all
      countries should have such immunization in place by 1997. At present, 50
      countries have a national policy of including hepatitis B vaccine as a routine
      part of their infant immunization programme--up from 25 countries in 1990. These
      countries represent 32% of the world's 145 million newborns, but 56% of the
      world's carriers. Several countries of 'low' endemicity are also recommending
      hepatitis B immunization of all newborns or adolescents (or both), realising that
      the strategy of 'high-risk group' immunization has failed to control HBV
      infection even in areas of low endemicity and that addition of hepatitis B
      vaccine to routine immunization schedules is highly cost-effective. All countries
      should establish working groups to examine the burden of disease due to HBV
      infection and the cost-effectiveness of adding hepatitis B vaccine to routine
      and/or adolescent immunization programmes.

PMID- 7571831
TI  - Proceedings of the International Congress. Action towards control of hepatitis B
      as a community health risk. Cannes 22-24 November 1993. Introduction.

PMID- 7571832
TI  - National infrastructures for delivery of hepatitis B vaccination to different age
      groups.
AB  - If hepatitis B vaccination is to be introduced into a universal vaccination
      programme, it must be given before young people become sexually active. Two age
      groups are of main interest: infants and early adolescents. In Australia, North
      America and Europe, vaccination programmes for infants are well established but
      not yet for adolescents. From a developmental point of view, targeting
      adolescents seems to be a demanding task. Nevertheless, there are examples of
      successful approaches: e.g. rubella vaccination in the UK, where since its
      introduction in 1976 the immunization coverage among 14-year-olds has remained
      high at 80-85%, or the more recent hepatitis B strategies in Italy and Spain,
      where young adolescents are included with high success rates. In summary, whereas
      the inclusion of HBV vaccine in the infant immunization programme is not a
      problem in most counties, the approach to adolescents needs more thought.

PMID- 7571833
TI  - Hepatitis B prevention in Europe: a preliminary economic evaluation.
AB  - The World Health Organization (WHO) estimates that about 350 million people in
      the world are carriers of the hepatitis B virus (HBV), 60 million of whom may die
      from liver cancer and about 45 million from cirrhosis. In the WHO European
      Region, which has a total population of 839 million inhabitants, the average
      number of acute hepatitis B cases reported in 1991 was approximately 160,000,
      giving an incidence of 19 per 100,000 population. This incidence rate varies from
      5 per 100,000 in western Europe to 22 per 100,000 in central Europe and 92 per
      100,000 in eastern Europe. Because of under-reporting and the fact that two
      thirds of infections are asymptomatic, the reported incidence rate considerably
      underestimates the true incidence of HBV in Europe. For this reason, we may
      multiply the number of reported cases by a factor of 6 (by 2 for under-reporting
      and by 3 for the symptomatic/asymptomatic ratio): an estimated 900,000 to
      1,000,000 infections of HBV occur in Europe each year. Approximately 90,000
      chronic infections will develop from these new cases. The spread of HBV can be
      controlled by universal infant or adolescent vaccination. A decision-tree-based
      analytical model was used to assess the clinical and economic impact of these two
      interventions. The model took into account incidence and prevalence rates of HBV,
      natural history of infection, compliance and effectiveness of vaccination, and
      direct and indirect costs. Data were obtained from the literature and from a WHO
      European survey. The cost-effectiveness ratio amounts to 6443 pounds and 4745
      pounds per infection prevented for neonatal and adolescent vaccination,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571835
TI  - VHPB: summary of strategies and recommendations. Viral Hepatitis Prevention
      Board.
AB  - The Viral Hepatitis Prevention Board (VHPB) believes that stronger action is
      needed to control hepatitis B. Vaccinating those identified as at 'high risk' has
      failed to make a significant impact on the epidemiology of the disease. Many
      people with hepatitis B do not fall into any of the 'classic' high-risk groups
      and efforts to reach these groups have been unsuccessful. The VHPB supports the
      recommendation of the World Health Organization (WHO) that hepatitis B vaccine
      should be incorporated into national universal vaccination programmes by 1997.
      The recommendation came initially from the Global Advisory Group of the Expanded
      Programme on Immunization and was endorsed in 1992 by the World Health Assembly,
      the governing body of WHO which consists of representatives of all WHO member
      states. The WHO Working Group on the control of viral hepatitis in Europe, which
      met in Munich in 1991, concluded that the routine immunization of infants and
      adolescents should receive the highest priority. Universal infant and adolescent
      strategies have their own benefits and drawbacks; the VHPB has looked carefully
      into the rationale for and against these strategies. The prerequisites for
      implementing these strategies are discussed. A combined infant and adolescent
      strategy emerges as having many of the advantages of the individual approach and
      fewer disadvantages. Universal vaccination is clearly the most effective strategy
      for preventing hepatitis B. Its timely and successful implementation, even in
      countries with medium and low prevalence, is a priority. There is no reason why
      hepatitis B should not follow the success of smallpox, polio, diphtheria and
      measles vaccination.

PMID- 7571834
TI  - Establishing a national universal vaccination programme.
AB  - The collaborative efforts of healthcare providers, governmental policy and law
      makers and the public are often needed to provide the pressure necessary to
      establish a national universal vaccination programme. Key initiatives for those
      beginning to establish such a programme are the following: secure a scientific
      consensus or base of support; clarify relevance of the subject to all concerned;
      increase awareness of everyone (providers and consumers); recruit and involve
      influential people (angels) for support; seek out agendas within which to review
      the topic; generate cost-benefit data; encourage a consensus to be reached;
      identify legislative pathways to be used; convince politicians of the value of
      such a programme; request budgeting and funding; and, finally, follow up with
      surveillance studies to demonstrate the benefits of the programme.

PMID- 7571836
TI  - Introduction to implementing universal vaccination strategies: experiences to
      date in North America and Europe.
AB  - There are various reasons why immunization of selective high-risk groups has not
      succeeded in controlling hepatitis B. Universal vaccination is a valid
      alternative and we can draw on the experience of countries that have introduced
      this strategy.

PMID- 7571837
TI  - Implementation in Italy of a universal vaccination programme against hepatitis B.
AB  - Italy was the first industrialized country to introduce mass vaccination against
      hepatitis B. Following the collection of epidemiological data on age-specific
      incidence rates of infection, a law was issued in 1991 which established
      mandatory immunization of neonates and 12-year-old adolescents. This strategy
      will lead to the protection of all subjects aged 0-24 years within 12 years and
      to the elimination of circulation of hepatitis B virus (HBV) in a few decades.
      The first data on compliance with vaccination, both in infants and in
      adolescents, indicate the success of the programme, which was helped by good
      vaccination delivery services and awareness of the risks of hepatitis B both by
      physicians and the public. A multi-centre study on protective antibody level and
      kinetics over time is in progress. Preliminary results show an excellent response
      to vaccination. High-risk strategies will continue by actively offering HBV
      vaccination free of charge to all those exposed to infection via occupation or
      life-style. The Italian policy of universal vaccination against HBV can therefore
      be regarded as a model for the introduction of mass immunization into other
      countries.

PMID- 7571838
TI  - Evolution of the Viral Hepatitis Prevention Board.
AB  - The Viral Hepatitis Prevention Board (VHPB), an independent, international group
      of experts, was formed in 1992 to raise awareness about the risks of viral
      hepatitis and the need to prevent the disease. The VHPB's first initiative was an
      Action on Hepatitis B as an Occupational Hazard, under the auspices of the
      Society of Occupational Medicine. The objectives of this action were to increase
      the protection of workers at risk from infection with hepatitis B. In 1993, the
      VHPB widened its scope and established an Action on Hepatitis B as a Community
      Health Risk, under the auspices of the European Public Health Association. This
      action aims to inform and educate the public and policy makers about the dangers
      of hepatitis B, its modes of transmission and how it can be prevented in the
      community.

PMID- 7571839
TI  - Implementing universal vaccination programmes: Spain.
AB  - Until 1990, the immunization policy against hepatitis B in Spain was selective
      high-risk vaccination. That policy failed to reduce the incidence of hepatitis B
      and the prevalence rates of chronic carriers. In 1991, Catalonia began a
      universal immunization programme targeted at 12-year-olds. Six other regions
      (Castilla-Leon, Valencia, Extramadura, Navarra, the Balearic Islands and Rioja)
      introduced vaccination programmes in 1992. In 1993, three more regions (Galicia,
      Castilla-La-Mancha and Pais Vasco) began immunizing young adolescents. This means
      that 12-year-olds in Spain are now included in vaccination programmes against
      hepatitis B.

PMID- 7571840
TI  - Implementing universal vaccination programmes: USA.
AB  - In the USA, the policy is that all infants receive vaccine against hepatitis B
      virus (HBV). It is considered that HBV vaccine can be readily integrated into the
      routine childhood immunization schedule without additional visits. Booster doses
      of vaccine are not currently recommended because protection lasts for at least 10
      years after vaccination. As with the other universal vaccination programmes, pre-
      or post-vaccination screening is not undertaken. Screening of all pregnant women
      for HBV surface antigen (HBsAg) and immunization of all infants of HBsAg-positive
      mothers has been continued.

PMID- 7571841
TI  - Universal hepatitis B immunization: the British Columbia experience.
AB  - Between 1980 and 1992 there was a 70-fold increase in reported hepatitis B cases
      in British Columbia (BC), to a rate of 32 per 100,000 population, more than three
      times the national average of 10 per 100,000. In BC, this disease is one of young
      adults--less than 5% of reported cases occur under the age of 15 years. While
      Canada remains an area of low endemicity where transmission is mostly sexual or
      as a result of lifestyle choices, programmes of targeted immunization of certain
      high-risk groups (neonates of infected mothers, household and sexual contacts of
      acute cases and selected healthcare workers) begun in the mid-1980s have failed
      to reduce the increasing rate of reported infection. In September 1992, an
      expanded programme of hepatitis B immunization was implemented in BC. The
      programme has two main components: universal immunization of a cohort of pre
      adolescent children in schools and broadened targeted immunization of groups at
      known elevated risk for transmission. The school-based programme involves
      provision of a three-dose series by public health nurses to all children in grade
      6 (age 11 years) for whom parental consent is given. During the 1992-1993 school
      year, more than 42,000 grade 6 students were eligible for hepatitis B vaccine and
      the three-dose series was completed by 91% of students throughout the
      province.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571842
TI  - Implementing universal vaccination programmes: Bulgaria.
AB  - Universal vaccination against hepatitis B virus (HBV) was introduced for all
      newborns in Bulgaria in August 1991, after a three-year selective immunization of
      babies born to HBsAg-positive mothers. In 1992, a coverage level of 71.3% was
      achieved. Since 1989, hepatitis B morbidity among infants shows a continuing
      downward trend with the lowest annual incidence rate, 0.3 cases per 100,000, in
      1992. This represents an 82% decrease compared to the preimmunization period. As
      strong epidemiological evidence exists that an early age of infection
      substantially increases the overall burden of chronic HBV infection, future
      expansion of vaccination coverage to include all children up to 6 years of age
      was considered an appropriate alternative to the existing policies.

PMID- 7571843
TI  - Interactive session. II.

PMID- 7571844
TI  - Congress overview.

PMID- 7571845
TI  - Congress objectives.
AB  - In 1993, the Viral Hepatitis Prevention Board (VHPB) recognized that selective
      vaccination of individuals at high risk from hepatitis B had failed to control
      the spread of hepatitis B. The Action towards Control of Hepatitis B as a
      Community Health Risk was therefore established to provide information and make
      recommendations on actions to take to combat hepatitis B in the community. The
      VHPB supports the World Health Organization (WHO) recommendation that universal
      hepatitis B vaccination for all infants and/or adolescents should be integrated
      into the national immunization programme in all countries by 1997. The VHPB met
      regularly throughout 1993 to consider the issues involved in implementing
      universal strategies and to develop practical solutions that can help all
      countries meet the WHO goal. During this congress the feasibility of implementing
      universal infant and/or adolescent vaccination strategies were explored by
      reviewing the seroprevalence data in Europe, development of cost-benefit models
      and progress in countries that have already implemented universal vaccination.
      With the delegates' input, resolutions were reached that will guide future action
      towards meeting the WHO goal and combating hepatitis B in the community.

PMID- 7571846
TI  - Aims and logistics of the workshops.

PMID- 7571847
TI  - Workshop group: Spain and Portugal.

PMID- 7571848
TI  - Workshop group: Germany and Switzerland.

PMID- 7571849
TI  - Workshop group: Belgium and The Netherlands.

PMID- 7571850
TI  - Workshop group: France.

PMID- 7571852
TI  - Workshop group: Italy.

PMID- 7571851
TI  - Workshop group: Greece.

PMID- 7571853
TI  - New approaches to Pseudomonas aeruginosa lower respiratory tract infections.
AB  - Since 1973, the occurrence of respiratory tract infections due to P. aeruginosa
      has increased associated with the development of broad-spectrum penicillins. A
      clinical entity, diffuse panbronchiolitis (DPB) is a representative disease of
      chronic P. aeruginosa infections in Japan. In this paper, recent advances of
      research on pathogenesis and treatments of chronic P. aeruginosa lower
      respiratory tract infections in our department are reported. We examined sputum
      from patients with chronic P. aeruginosa infections under the electron
      microscope. Mucoid type of microcolonies were observed with fibrous matrix of
      exopolysaccharide. Neutrophils were found to be partially surrounding the
      microcolony in an attempt to defense. Debris was formed mainly by the destruction
      of the neutrophils. Most neutrophils were found full of phagocytized debris.
      These data support that instead of phagocytizing bacteria, neutrophils
      phagocytized debris and bacteria were not completely eradicated. This might be a
      factor in the pathogenesis of persistent colonization of P. aeruginosa. In the
      airways of patients with chronic airway diseases (CAD), neutrophils enhance the
      recruitment of more neutrophils through the production of neutrophil chemotactic
      factors such as interleukin-8 (IL-8) and LTB4, perpetuating a cycle of
      inflammation in the lung. We demonstrated increased levels of IL-8, a chemotactic
      cytokine, in bronchoalveolar lavage (BAL) fluid from patients with CAD associated
      with P. aeruginosa infections. We also documented a significant correlation
      between neutrophil numbers and IL-8 levels or IL-1 beta levels or neutrophil
      elastase levels in BAL fluids from patients with CAD. By immunohistochemical
      studies and in vitro data, three major sources of IL-8 in the airways of CAD
      patients were found to be alveolar macrophages, bronchial epithelial cells, and
      migrated neutrophils. In Japan, the clinical effectiveness of oral erythromycin
      (EM) for CAD, including DPB seems to be established, but its pharmacological
      mechanism remains unclear. In addition, we found a marked decrease of IL-8 levels
      in BAL fluid from two patients with CAD after treatment with EM. Therefore, we
      postulated that EM inhibited IL-8 production by stimulated respiratory cells. EM
      and Roxythromycin, suppressed IL-8 production in Pseudomonas-stimulated
      neutrophils in a dose-dependent manner. 1 alpha, 25-dihydroxy vitamin D3 also
      inhibited neutrophil-derived IL-8. Our data encourage the development of new anti
      IL-8 agents against persistent P. aeruginosa lower respiratory tract infections.

PMID- 7571854
TI  - [Sudden cardiac death, a worldwide problem].
AB  - Sudden death is an internationally recognized problem in the industrialized
      world. In Maastricht, research is performed to determine the characteristics and
      circumstances of persons who die suddenly outside the hospital. It appeared that
      sudden death usually occurs at rest (in 80% of the cases), and often at home.
      Cardiac complaints preceded sudden death in only 60% of the cases. Patients with
      a cardiac history and admitted to the Cardiology department are often not
      recognized before discharge to be at high risk for sudden death outside the
      hospital. The conclusion is, if one wants to decrease the number of sudden deaths
      outside the hospital, more attention has to be paid to optimalization of
      resuscitation efforts outside the hospital. A group who needs special attention
      are family members of cardiac patients, because sudden death usually occurs at
      home.

PMID- 7571855
TI  - Unraveling the secrets of Histoplasma capsulatum. A model to study morphogenic
      adaptation during parasite host/host interaction.
AB  - Early in the developmental period of microbiology, Pasteur first observed the
      phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew
      as a filamentous mold aerobically on the surface of broth cultures but at the
      bottom of the flask where the environment was anaerobic it reproduced as budding
      yeast cells. Several infectious fungal pathogens of humans, namely Histoplasma
      capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix
      schenkii, and Coccidioides immitis change from a multicellular filamentous form
      to an unicellular morphology when they invade tissues. The ability of pathogenic
      fungi to assume a different shape is referred to as dimorphism. This phenomenon
      has intrigued clinicians, and medical mycologists since its discovery at the turn
      of the century. The ability of pathogens to initiate infection, invade host
      tissues and survive in mammalian hosts is critically linked to the induction of
      specific gene products. In dimorphic fungi, developmentally regulated gene
      expression is particularly important, since they may exist in phylogenetically
      distinct hosts with different body temperatures. Using Histoplasma capsulatum as
      a model to study parasite-host interactions at the biochemical and molecular
      level, my laboratory has attempted to relate the clinical spectrum of disease to
      natural variations in the characteristics of this organism and to adaptations it
      must make as a saprobe and a parasite. Histoplasma capsulatum is the etiologic
      agent of histoplasmosis, a respiratory infection that is world-wide in
      distribution. As a saprobe in soil it is mycelial, but it becomes a budding yeast
      as a parasite in susceptible hosts. These morphological phases can be reversibly
      reproduced in vitro by shifting the temperature from 25 degrees C, at which it is
      mycelial, to 37 degrees C, when it becomes a budding yeast. The process of
      mycelial-to-yeast conversion is of particular interest since it is triggered by
      an increase in temperature and conversion to virulence. Viable mycelial fragments
      and conidia become airborne and enter the pulmonary tract by inhalation after
      which the fungus rapidly disseminates to other organs. Progressive disseminated
      histoplasmosis along with candidiasis, cryptococcosis, and invasive aspergillosis
      are opportunistic fungal infections in patients who are immunosuppressed or
      otherwise debilitated. Importantly, they are diagnostic hallmarks of acquired
      immunodeficiency disease syndrome (AIDS). The clinical features of these
      infections and the genetic characteristics of the etiologic agents present unique
      parasite-host interactions that make them valuable research models to study. In
      the infected host, Histoplasma capsulatum encounters various environmental
      stresses to which it adapts by regulating the expression of specific
      genes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571856
TI  - [Tuberculosis: current epidemiological-clinical problems].
AB  - Tuberculosis (tb) mortality, morbidity and infection prevalence were very high in
      Belgium and in the other industrialised countries during the previous century,
      and the first half of this century. Therefore tb was an "export" pathology,
      especially towards developing countries. At the end of this century tb
      epidemiological indices reached very low levels in the Western world, while tb
      became endemic in several non-Western countries and so it actually has become an
      "import" pathology. In the USA, as well as in many European countries, the tb
      morbidity incidence started to increase again about ten years ago. The risk
      groups are, however, not identical in the USA and in Belgium. In the USA, it is
      particularly the AIDS-epidemic that is the cause of half of the increase in tb
      incidence; in addition social outcasts, homeless and IV-drug addicts are
      important risk groups and due to their poor therapy compliance they are
      responsible for the many multidrug resistant forms emerging in New York and other
      large cities. In Belgium elderly males are an important risk group with a tb
      incidence of 50 per 10(5) in 1993 (versus an overall incidence of 15 per 10(5)).
      Besides, in this group the diagnosis is often made late. A second important risk
      group consists of allochthones, with an incidence of 54 per 10(5), especially non
      Western allochthones, with an incidence of 120 per 10(5). Above all others are
      the asylum seekers with an estimated incidence of 400 per 10(5) (which
      undoubtedly is an underestimation). In Belgium, the AIDS-epidemic does not
      represent a major problem so far; only 3.5% of the tb-cases have AIDS or are HIV
      positive, and 50% of these are immigrants. Finally, also multidrug resistance is
      no real problem, since resistance against isoniazide and rifampicin has been
      found in only 0.5% of the tb-cases. Contact persons of tb-cases, however, still
      remain a very important risk group with an incidence of more than 200 per 10(5).
      The danger is especially great for as long as the diagnosis has not been made in
      the source of infection and no therapeutic measures have been taken. While the
      overall tb-threat increased in the last decade, the tb-organisations (in Flanders
      the VRGT, Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding)
      have been more or less dismantled, which in consequence may lead to problems in
      the future!(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571858
TI  - [Arsenic, lead and cadmium in home-made preserves of fruit and vegetables from
      previous years. 2. Climbing beans since the harvest year 1913].
AB  - Levels of arsenic, lead and cadmium in climbing beans of harvest years 1913 to
      1986, home-sterilized in glass jars, were determined by atomic absorption
      spectrometry. Concentrations of arsenic showed a decreasing trend from 1913
      (highest value) to 1955, all levels being above 5 micrograms kg-1, whereas after
      1955 only levels below 5 micrograms kg-1 were found. Presumably the formerly
      allowed arsenic containing pesticides are responsible for this. No clearly
      increasing or decreasing trend in the concentrations of lead and cadmium were
      observed.

PMID- 7571857
TI  - The status of trace elements in staple foods from the former Federal Republic of
      Germany. I. Contents of 11 trace elements.
AB  - In representative samples of bread cereals and cereal products from the former
      Federal Republic of Germany (FRG) the status of 11 trace elements was analysed in
      1989. It is demonstrated that the results are quite representative for the former
      FRG as compared with results published in the previous 15 years. The sampling
      technique for staple foods is explained. A number of certified standard reference
      materials were used to validate the analytical methods employed.

PMID- 7571859
TI  - [Arsenic, lead and cadmium in home-made preserves of fruits and vegetables from
      previous years. 3. Peaches since the harvest year 1931].
AB  - Levels of arsenic, lead and cadmium in peaches of harvest years 1931 to 1987,
      home sterilized in glass jars, were determined by atomic absorption spectrometry.
      Concentrations of arsenic showed a slightly decreasing trend during the years.
      Lead levels in unpeeled peaches were clearly higher than in peeled fruits.
      Cadmium levels scattered over a wide range and showed no time trend.

PMID- 7571860
TI  - [Mineral and amino acid contents of edible, cultivated shii-take mushrooms
      (Lentinus edodes)].
AB  - World wide about 200,000 tons of shii-take mushrooms (Lentinus edodes) are
      produced per year. Different positive biological effects are known
      (anticarcinogenic, anticholesterol, immunostimulating effects), but the mineral
      contents and amino acid composition of caps and stipes are still little
      investigated. The concentrations of minerals are in general lower than those in
      the cultivated white mushroom (Agaricus bisporus) and in the oyster mushroom
      (Pleurotus ostreatus). The greatest differences are found in the concentrations
      of potassium, phosphorus, calcium, copper, strontium, manganese and zinc. The
      concentrations are higher in caps than in stipes. The total amino acid content is
      15.24% in caps and 11.35% in stipes (dry matter) and thus in general half of the
      concentration of cultivated champignon. The amounts of Phe, Gly, His, Arg, Ile
      and Met are relative higher than in Agaricus fruit bodies.

PMID- 7571862
TI  - Dependence of the 12-methyltridecanal concentration in beef on the age of the
      animal.
AB  - The content of 12-methyltridecanal (12-MT), which contributes greatly to the
      characteristic aroma of stewed beef, was determined by a stable isotope dilution
      assay in meat samples from nine bovine animals of different ages. The results,
      which were related to the amount of phospholipids (PL), indicate that 12-MT
      content increases with the age of beef, e.g., from 36 micrograms.g(-1) PL in a 4
      month-old calf to 810 micrograms.g(-1) PL in an 8-year-old cow. The increase of
      12-MT content in PL per month varied between 8.4 and 10.9 micrograms.g(-1) PL
      (mean: 9.3 +/- 0.78 micrograms.g(-1) PL). Possibly 12-MT content is suitable as
      an indicator for the estimation of the age of a beef sample.

PMID- 7571861
TI  - [B-vitamins (thiamine, vitamin b6, pantothenic acid) in lean muscle tissue of
      growing cattle of the German Simmental breed under different feeding
      intensities].
AB  - In a comparative slaughter experiment the thiamin, vitamin B6 and pantothenic
      acid content of lean tissue of foreloin of growing cattle was determined by whole
      body analyses. 54 bulls, 45 heifers and 45 steers were fed until a live mass of
      200 kg, 350 kg, 425 kg (only heifers) 500 kg and 575 kg, 650 kg, respectively
      (only bulls and steers). One half of each carcass was divided into 13 cuts and
      afterwards the cuts were each divided into lean, adipose and bone tissue and
      tendons. The lean tissue of the foreloin was subjected to analysis of thiamin,
      vitamin B6 and pantothenic acid. The mean thiamin content of 0.75 mg kg-1 fresh
      matter (200 kg live mass) decreased with rising live mass and under intensive
      feeding conditions in bulls and steers to 0.53 mg and in heifers to 0.61 mg.
      Restrictively feeding caused a mean thiamin content of 0.60 mg per kg fresh
      matter in bulls, steers and heifers. Under both feeding conditions in the lean
      tissue of the foreloin on average a vitamin B6 content of 2.6 mg (bulls), 3.1 mg
      (heifers) and 3.0 mg kg-1 fresh matter (steers) was analysed. A mean content of
      pantothenic acid of 2.6 mg kg-1 fresh matter was determined in bulls independent
      of live mass and feeding intensity. In heifers the content of pantothenic acid on
      average was 3.0 mg under intensive feeding system and 2.6 mg under low feeding
      conditions, whereas steers reached contents of 2.7 mg (high feeding) and 2.2 mg
      kg-1 fresh matter (low feeding).

PMID- 7571863
TI  - [Experiments with sausage meat on the formation of N epsilon
      carboxymethyllysine].
AB  - In model experiments the influence of ingredients normally used for sausage
      production to a meat homogenate on the formation of N epsilon-carboxymethyllysine
      (CML) was investigated. The formation of CML is obviously more promoted from the
      reaction of ascorbate with lysine than from that of glucose with lysine. The
      addition of ascorbate in a practical concentration yielded 35 mg, the addition of
      glucose only 23 mg compared to 17 mg CML/kg protein in the control sample. The
      addition of diphosphate in a practical concentration besides glucose
      significantly increased the CML values from 23 mg to 30 mg CML/kg protein. On the
      other hand, nitrite did not enhance the formation of CML (21 mg/kg protein) in
      the sausage when used in concentrations usually applied in meat processing.
      Generally the values found in the meat products are quite low compared to data in
      other foods like milk products.

PMID- 7571864
TI  - Purification and isoenzymic composition of glycogen phosphorylase b from normal
      and abnormal (PSE) muscles.
AB  - Ion exchange chromatography and preparative isoelectric focusing allowed the
      identification of five isoenzymes of glycogen phosphorylase b from the
      longissimus dorsi muscle of normal pigs and those prone to having pale, soft and
      exudative (PSE) muscle. The isoelectric point of the isoenzymes varied in the pH
      range from 6.29 to 6.55. One of them, with an isoelectric point at about a pH of
      6.49, accounts for 65% of the total glycogen phosphorylase b activity. No
      significant differences between normal and PSE-prone pigs were observed in the
      total glycogen phosphorylase b activity and in the isoenzyme distribution
      pattern. It is concluded that the fast glycogen turnover in PSE-prone pigs is not
      due to a different isoenzyme pattern of phosphorylase b.

PMID- 7571865
TI  - [Spelt wheat and celiac disease].
AB  - Spelt wheat (Triticum spelta L.) has not been investigated for the toxicity on
      coeliac disease patients until now. Because clinical studies are out of
      considerations for ethical reasons, spelt wheat and coeliac-active bread wheat
      (Triticum aestivum L.) were compared by the analysis of N-terminal sequences of
      alpha-gliadins, which have been proposed to be responsible for the toxic effect.
      The gliadin fractions of the spelt wheats 'Roquin' and 'Schwabenkorn' and of the
      bread wheat 'Rektor' were preparatively separated by RP-HPLC and major alpha
      gliadin components were then compared by N-terminal sequence analysis. The
      results did not reveal any significant difference between spelt and bread wheats
      within the first 25 positions. For the determination of sequences further from
      the N-terminus, the gliadin fractions of the spelt wheats were hydrolyzed with
      pepsin and trypsin. The resulting peptides were successively separated by gel
      permeation chromatography and RP-HPLC. Those peptides derived from the N-terminal
      part of alpha-gliadins were identified by reference peptides isolated previously
      from bread wheat [this journal 194: 229 (1992)]. Retention times upon RP-HPLC and
      amino acid compositions of corresponding peptides confirmed the identity of spelt
      and bread wheat concerning the N-terminal sequences of alpha-gliadins from
      position 3 to 56. For these reasons, it can be concluded that spelt wheat is a
      coeliac-toxic cereal and has to be avoided by coeliac patients.

PMID- 7571866
TI  - [Composition, physico-chemical properties and molecular superstructure of dietary
      fiber preparations of the cellan type].
AB  - Dietary fiber preparations of "cellan" type were prepared from apples, white
      cabbage, sugar beet pulp, soy hulls and wheat bran by treatment with amylolytic
      and proteolytic enzymes as well as by chemical extractions. Scanning electron
      microscopic examinations show different morphological structures of the
      preparations and a high maintenance of native biomolecular superstructure. The
      content of pectin, protein, polysaccharide-hexoses and -pentoses and the
      composition of monosaccharides (also after their treatment with 4 or 8% sodium
      hydroxide) were determined. The cellans possess waterbinding capacities (WBC)
      between < 10 and > 25 g H2O/g and waterholding capacities between < 10 and > 50 g
      H2O/g. The WBC is related to the internal surface; it diminishes after treatment
      with NaOH. The interactions between the cellans and the adsorbed water were
      characterized by NMR-spin-lattice relaxation time T1. The molecular mobility
      increases as the water content grows. The T1-values of dried cellans decreased
      with increasing degree of moisture before drying. The supermolecular structure is
      comparatively disordered. Only in case of soy cellan a crystalline cellulose-I
      modification could be identified by X-ray-diffraction pattern, esp. after NaOH
      treatment. The low degree of order of cellans was observed in the 13C-NMR
      spectra, too. Only the soy hull preparation resulted in a spectrum corresponding
      to well-ordered cellulose. The botanic source has an essential influence on the
      physico-chemical properties of dietary fiber preparations of cellan type.

PMID- 7571867
TI  - A method to mimic and to study the release of flavour compounds from chewed food.
AB  - A method for analysing the flavour release from chewed food has been developed.
      Flavour release is studied in an artificial mouth simulating the process of
      chewing and using fluid model systems, in our case aromatised oil in water
      emulsions. The fast transfer of volatile substances from the chewpulp into the
      gaseous phase is followed up by comparing six quickly taken gas samples. Volatile
      substances are analysed by means of a special technique which includes
      cryofocusing and capillary gas chromatography. As a wide spectrum of individual
      volatile substances is considered, systematic investigations into the flavour
      release from food under mouth-typical conditions are possible.

PMID- 7571868
TI  - [Determination of dithiocarbamate residues in foodstuff by head space gas
      chromatography and flame photometric detection].
AB  - With headspace-technique in conjunction with a flamephotometric detector (FPD) a
      fast and sensitive method for the determination of dithiocarbamates from organic
      foodstuff is presented. The dithiocarbamates are treated with tin-(II)-chloride
      and determined quantitatively as carbon disulfide (CS2). The evaluation of the
      data is performed by calibration curves.

PMID- 7571869
TI  - The status of trace elements in staple foods. II. Some effects of cereal and
      potato processing.
AB  - The effects of food processing on some cereal and potato products are discussed
      with respect to the status of 11 trace elements. The influences of milling, bread
      making and cooking of potatoes on the contents of trace elements are
      demonstrated. It is shown that these recently obtained results are quite
      representative for the former federal Republic of Germany (FRG) as compared with
      results published previously. Average intake levels of undesired elements such as
      cadmium and lead, as well as of essential elements such as calcium, copper, iron,
      magnesium, manganese, molybdenum, nickel, selenium and zinc via consumption of
      cereal and potato products are calculated.

PMID- 7571871
TI  - The formation of biogenic amines by fermentation organisms.
AB  - A total of 523 strains representing 35 species related to food fermentation
      organisms of practical importance were investigated for their potential for
      formation of biogenic amines (BA). The investigation was performed with resting
      cells in phosphate buffer (pH 5.5) and the formation of the following BAs was
      followed: putrescine, cadaverine, histamine, tyramine and 2-phenylethylamine. No
      potential was observed in species of lactococcus, Leuconostoc, Pediococcus,
      Streptococcus and several Lactobacillus spp., such as L. Pentosus and L. sake. A
      remarkable potential to form BA was observed in strains of carnobacteria,
      Lactobacillus buchneri, L. curvatus, L. reuteri, Staphylococcus carnosus and, to
      a lesser extent, in L. alimentarius, L. brevis, L. bavaricus, L. delbrueckii ssp.
      lactis, Micrococcus spp. and S. piscifermentans. In well known species with a
      practical function in the fermentation of dairy products, wine or cabbage a
      potential was observed for few strains only. In view of their role as starters in
      food fermentation, or their potential use in protective cultures and as
      probiotics, BA formation by the organisms has to be taken into consideration by
      selecting appropriate strains.

PMID- 7571870
TI  - Effect of gamma-radiation on migration behaviour of dioctyladipate and
      acetyltributylcitrate plasticizers from food-grade PVC and PVDC/PVC films into
      olive oil.
AB  - Food-grade PVC and PVDC/PVC films containing 28.3% dioctyladipate (DOA) and 5.0%
      acetyltributylcitrate (ATBC) plasticizers, respectively, were brought into
      contact with olive oil and were irradiated with gamma-radiation [60Co] at doses
      equal to 4 kGy and 9 kGy corresponding to "cold pasteurization". Irradiation was
      carried out at 8-10 degrees C and samples were subsequently stored at 4-5 degrees
      C. Contaminated oil samples were analysed for DOA and ATBC at intervals between 7
      h and 97 h of contact, using an indirect GC method. Identical nonirradiated
      (control) samples were also analysed for DOA and ATBC content. Results showed no
      statistically significant differences in migrated amounts of DOA and ATBC between
      irradiated and non-irradiated samples. Neither were differences observed between
      samples irradiated at 4 kGy and 9 kGy. This was supported by identical IR spectra
      recorded for irradiated and non-irradiated samples and leads to the conclusion
      that at such intermediate radiation doses (< or = 9 kGy) the migration
      characteristics of both PVC and PVDC/PVC films are not affected. The amount of
      DOA that migrated into olive oil was dependent on time, reaching equilibrium
      after approximately 47 h of contact (302.8 mg/l). The amount of ATBC that
      migrated into olive oil was non-detectable (< 1 mg/l) for all samples stored at 4
      5 degrees C after 97 h. In non-irradiated samples (PVDC/PVC in contact with oil)
      stored at 20 degrees C, small amounts of migrated ATBC were determined (3.3 and
      5.1 mg/l after 29 h 94 h of contact respectively).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7571872
TI  - [Comparative investigations of mycotoxological status of alternatively and
      conventionally grown crops].
AB  - 100 samples of rye and 101 samples of wheat coming out of both conventional and
      alternative or ecological production were investigated for contamination with
      mycotoxins with interest for our degree of latitude. Deoxynivalenol (DON) was
      found with thin-layer-chromatography in 131 of 201 samples altogether. A top
      level of 1250 micrograms DON kg-1 in rye of alternative offspring was detected.
      The average burden in contaminated rye coming from ecological production was 427
      micrograms kg-1 and a mean level of 160 micrograms kg-1 resulting in rye out of
      conventional growth conditions. In wheat, conventionally grown yield showed
      slightly lower contamination (mean levels of 420 micrograms DON kg-1 towards 486
      micrograms kg-1). The toxins 3-acetyl-deoxynivalenol, nivalenol and fusarenone X
      were detected in some samples by thin-layer-chromatography. This results could
      not be confirmed by gas chromatography -mass spectrometry. Zearalenone was found
      in 40 out of the number of 201 samples of grain by HPLC with fluorescence
      detection. An average of 6 micrograms and 24 micrograms zearalenone kg-1 in
      conventionally and alternatively grown wheat and 4 micrograms and 51 micrograms
      zearalenone kg-1 in conventionally and alternatively produced rye was detected.
      The highest finding of zearalenone was 199 micrograms kg-1 in alternatively grown
      rye. Skin toxicity testing did not show any reference of contamination with type
      A-trichothecenes. No correlation between contamination of zearalenone or
      deoxynivalenol and thousand-kernel-weight was detected.

PMID- 7571873
TI  - [Managing violence: cooperation between adolescent welfare and child and
      adolescent psychiatry as a chance for improvements].

PMID- 7571874
TI  - [Behavior therapy in children and adolescents: a utilization study].
AB  - Outpatient behavior therapy has been paid for in the Federal Republic of Germany
      since 1980 as a service of the health insurance system that covers most of the
      population. This therapeutic approach is used with children, adolescents and
      adults, but up to now it has played only a minor role in the treatment of
      psychological and psychiatric problems in children and adolescents. A content
      analysis of 221 applications for approval of long-term therapy for children or
      adolescents provided information on sociodemographic data, symptoms, diagnoses,
      treatment goals and treatment methods. Data were also obtained on the patients'
      social situation. The analysis suggests that mainly 7- to 11-year-old boys
      undergo treatment. The number of girls receiving treatment increases during
      puberty, and during adolescence more girls are treated than boys. Applications
      for outpatient behavior therapy are predominantly for developmental disorders,
      hyperkinetic disorders, emotional disorders, phobias, enuresis, adjustment
      disorders, conduct disorders and eating disorders. The main treatment goals are
      the development of new behavioral skills and the maintenance of or strengthening
      of behavior that is incompatible with the symptoms. Cognitive-behavioral methods
      are frequently used.

PMID- 7571875
TI  - [The effect of valproic acid monotherapy on behavior and cognitive performance of
      children with idiopathic generalized epilepsy].
AB  - Valproic acid (VPA) currently plays an important role in the treatment of several
      different types of epilepsy. Especially in children and adolescents, VPA is used
      because of a minimum of adverse effects and generally little impact on cognitive
      and psychomotor functions. However, reports in the literature regarding the
      influence of VPA on behavior and cognitive performance and on EEG parameters vary
      widely. We investigated the effect of VPA monotherapy on behavioral components
      (attention, concentration, inhibitory control), cognitive efficiency (motor
      reaction time, learning, retention) and evoked potentials in 19 children aged 6
      to 14 years with idiopathic generalized epilepsy and compared the results with
      those of healthy controls matched for age. In addition, we analyzed the serum
      levels of VPA and some of the VPA metabolites in all of the children with
      epilepsy immediately before the psychophysiological assessments. Our results show
      marked differences between the children with epilepsy and the healthy controls in
      all types of behavior and cognitive performance assessed. Abnormal behavior
      (disturbances of attention and concentration, impulsive behavior patterns) and
      significant changes in evoked potentials appear to be correlated with serum
      levels of VPA and certain VPA metabolites.

PMID- 7571876
TI  - [Follow-up of psychiatric disorders and specific developmental delay disorders in
      special education students].
AB  - In a prospective longitudinal study 72 children who were attending a special
      school for children with learning disabilities in Erlangen were examined in 1990
      and again in 1992/93. At the first examination the children's mean age was 7
      years 1 month and at the second 8 years 10 months. The sample contained many more
      boys than girls. Reported here are the findings on the course of the psychiatric
      disorders and the specific developmental disorders of speech and language and
      motor function. There was a marked decrease in the prevalence of psychiatric
      disorders. Of the 17 children with a psychiatric disorder at follow-up, 13 (76%)
      also had a disorder at the start of the study and of the 23 with a psychiatric
      disorder at the start 13 (57%) still had a disorder at follow-up. Children with
      enuresis and those with disturbances of activity or attention had the best
      prognosis. The special school had a positive effect on conduct. The prevalence of
      specific developmental disorders also decreased over the two-year period. As
      expected, specific speech articulation disorders had the best prognosis. All
      other disorders had a poor prognosis. Increases in prevalence were mainly the
      result of different cutoff points for a given diagnosis at different ages. The
      high number of specific disorders of motor function at both time points is
      especially noteworthy.

PMID- 7571877
TI  - [Possibilities of concomitant drug treatment of stuttering in childhood and
      adolescence].

PMID- 7571878
TI  - [The reciprocal reflecting team. A further modification of the reflecting team in
      inpatient child psychiatry].
AB  - The purpose of reflecting teams is to instigate change in systems that have
      become bogged down, including helper systems. The modifications that have been
      made in the Andersen reflecting team since it was first described (1987) are
      summarized. The reflecting team technique derives from family therapy and is
      epistemologically based on the radical constructivism of Bateson (1981), von
      Forster (1985), von Glaserfeld (1985) and others. Making use of the information
      resources of the key workers on our child psychiatry unit, we developed another
      variation, a "reciprocal reflecting team". This model is suitable for use in a
      clinical setting because it involves all of the key individuals working with a
      given child. The fundamental difference between our model and Andersen's is that
      initially we have no reflecting phase for psychotherapists. Rather, we start with
      a reflecting sequence in which the multidisciplinary clinical team discusses
      observations, information and hypotheses about the index patient and his or her
      family. Our impression is that our results are compatible with those of Hoger et
      al. (1994) that family therapy using a reflecting team effects positive change in
      two of three cases. Because we have no follow-up data and our sample is still
      very small we base this on spontaneous positive feedback from the family members
      regarding their satisfaction with treatment. Further evidence is provided by
      clinical observations on the children's behavior and on changes in family
      interaction.

PMID- 7571880
TI  - [Critique of the German validation of the Child Behavior Checklist (Dopfner et
      al., 1994)].

PMID- 7571879
TI  - [Use of hypnotherapy techniques within the scope of behavior therapy treatment of
      learning and behavior disorders in children--2 case reports].
AB  - Most of the children on our ward suffer from severe speech and language
      disorders, dyslexia, other learning disabilities and conduct disorders. We
      treated 10 selected children with cognitive behavior therapy combined with
      hypnotherapy. To demonstrate this treatment strategy we report on a 9-year-old
      girl and a 9-year-old boy from this group and give a short description of the
      hypnotic communication patterns used in conjunction with behavior therapy. The
      therapy combination proved to be a useful one. The children's social competence
      and learning motivation improved throughout the general therapeutic setting. The
      children's responses to relevant questionnaires confirmed these findings. Our
      results suggest that an increase in treatment efficacy can be achieved by using
      hypnotherapeutic patterns in conjunction with behavior therapy in the treatment
      of children with the disabilities mentioned.

PMID- 7571881
TI  - [Structure and structural disorder].
AB  - One of the central tasks of psychodynamic diagnosis, next to determining
      intrapsychic conflicts, central relational patterns, and subjective forms of
      experiencing is assessing the psychic structure or the structural disorder. This
      article develops the structure term from object relationship theoretical, ego
      psychological, and self-psychological concepts of psychoanalysis. This "Structure
      of the self in the relationship to others" thus obtained is described with six
      structural criteria (self-perception, self-control, defence, object perception,
      communication, attachment). In order to be able to distinguish the extent and the
      quality of structural disorders four structure levels of integration based on
      psychoanalytic experience in the out-patient and the in-patient setting are
      differentiated. A basis for an operationalization is then made; it is made in the
      system OPD (Operationalized Psychodynamic Diagnostics). First studies regarding
      practicalibility and reliability are promising.

PMID- 7571882
TI  - [Structural thinking in psychoanalysis].

PMID- 7571883
TI  - [Countertransference in homoerotic transference].
AB  - Until now psychoanalytic training and literature have hardly considered the
      transference love of homosexual patients. We summarized the scarce literature and
      related it to the background of our knowledge of heterosexual transference love.
      The discussion leaves no doubt that, like the heterosexual, homosexual
      transference love must be read on all levels of psychosexual development instead
      of reading it on only one and definitely not on an amorphous "preoedipal" level.
      This is particularly true for the level of the adult homosexual patient, as the
      case history demonstrates.

PMID- 7571884
TI  - [Interactive production of resistance].
AB  - Already the first version of the resistance concept as a force of the paint
      against which Freud had to summon psychic work names an interactive event. The
      conversational-analytic examination of therapeutic dialogs may bring to light
      that resistances are not just embedded in the interpersonal relationship of
      patient and psychotherapist, but are produced with verbal and non-verbal means
      with which patient and psychotherapist handle their interactions. This is
      described with a micro analysis of the therapeutic interaction in videographed
      sequences from an analytic oriented short therapy of a patient with phobic and
      compulsive symptoms.

PMID- 7571885
TI  - [Fine tuning an analytic supervision].
AB  - With a casuistry we tried to show how disturbances in the free-floating attention
      of the reporter, which take on the character of micro-symptoms, can be based on
      the structural similarity of experience moments of therapist and patient; we were
      able to show how these experience moments influenced the report of an analytic
      supervision group. Only after a third person joined the others, the triangular
      relationship within the supervision, was it possible to consciously perceive the
      structural similarity. Within such a triangular relationship, where the person
      opposite can always also be seen through the eyes of a third party, it is
      possible that the capabilities of self-reflection and self-evaluation, which
      characterize the analytic attitude, can develop via identifications.

PMID- 7571887
TI  - [The significance of latent anthropology for psychotherapeutic treatment].

PMID- 7571886
TI  - [Validity of the Narcissism Inventory (Denecke and Hilgenstock)].
AB  - For investigating the validity of the Narzissmusinventar 27 somatic and psychic
      healthy men aged between 30 and 45 were tested with the Narzissmusinventar, the
      Fragebogen zur Erfassung von Aggressivitatsfaktoren, the State-Trait
      Angstinventar and the Fragebogen zur Messung der Kontrollambitionen. Moreover a
      structured interview for the evaluation of type A behavior was administered.
      Correlative statistical analyses showed in the sense of construct validity that
      the dimension of the "bedrohtes Selbst" ("threatened self") is characterized by
      anxiety, feelings of insufficiency and aggression. The other subscales of the
      Narzissmusinventar correlate only with a few variables of the other tests and the
      speaking behavior. These subscales evaluate the narcissistic personality traits
      which the other instruments we used in our investigation are not able to reflect.

PMID- 7571888
TI  - [Economic evaluation of medical therapy--methodological principles].
AB  - Economic evaluations represent an excellent instrument to prepare decisions in
      health care with special reference to the allocation of resources as well as the
      utilisation of new and existing medical interventions and therapies. These
      evaluations require the identification and assessment of the costs and benefits
      of the various options prior to their integration in the economic calculations.
      The basic principles and concepts of economic evaluations are reviewed and
      discussed. In addition the significance of clinical, resp. medical economics will
      be reviewed as an important tool for the clinician.

PMID- 7571889
TI  - [Costs of safety of blood and blood products].
AB  - The safety of blood and blood components in transfusion medicine has become a
      very important factor. While diagnostic and therapeutic medical procedures need
      an increasing amount of special blood products, increasing demands on safety
      result in a reduction of blood donations. Considerable costs are caused by the
      requirement of self-sufficiency, additional assays to detect virus infections
      such as HIV, HCV and others, virus inactivation of blood and plasma, storing of
      plasma in quarantine, increase of autologous blood donation, and a great many of
      further steps to improve the safety in transfusion medicine. To obtain absolute
      safety, efforts are required that necessarily exceed the financial capacity of
      our health system. Because of budget limitations increasing costs of blood
      products will interfere with progress of other areas of health care. In addition
      ethical aspects of the use of funds have to be taken into consideration.

PMID- 7571890
TI  - [Socioeconomic studies of hemostaseologic therapy and anticoagulation].
AB  - Since hemostaseologic therapies have a great impact on the budget of public
      health insurance companies, the therapy of hemophilia, prophylaxis of thrombosis
      and thrombolysis should be evaluated in a socioeconomic way. The substitution
      therapy in hemophilia is consuming a great deal of health care resources. The
      patients require an expensive, chronic therapy which enables them to be
      integrated in a normal social life. A lot of patients get a prophylaxis against
      thrombosis. Anticoagulants have to be valued with respect to their cost
      effectiveness-relation. If thrombolysis is evaluated economically, one will have
      to consider carefully the high letality of thrombosis, the savings for the
      prevention of an operation and the high impact of this therapy on health care
      bills. The steady increase in health care costs emphasizes the necessity of
      health economics. Physicians should run socioeconomic evaluations to prove the
      use of different medicines and therapies and to represent the clinical point of
      view and the part of the patients.

PMID- 7571891
TI  - [Ambulatory surgery in the hospital--analysis of a 1978-1994 patient sample].
AB  - In the outpatient department of the University hospital of the Technology
      University Dresden ambulatory surgery has been performed since 1965. The patients
      of 16 years were analyzed. From 1978 till VI/1994 we have carried out 13948
      elective operations. The personal wish of a cooperative patient without risk
      factors and an orderly social surrounding are the prerequisites for carrying out
      outpatient operations. Applied anaesthetic techniques were: general anaesthesia
      9.2%, spinal anaesthesia 7.1%, sacral anaesthesia 14.8%, nerveblock of the upper
      extremity 11.1 and infiltration anaesthesia 57.8%. On the day of operation 61
      patients had to be admitted to the hospital because of intraoperative events,
      expansion of the operation and complications of anaesthesia. Between the first to
      eight postoperative day 23 patients were hospitalised due to bleeding and 1
      patient due to a wound infection. After aseptic elective operations 33 patients
      (0.35%) and after proctology operations with primary wound closure 10% of the
      patients developed wound infections. The cooperation of the general practitioner
      must be ensured in the post-operative days. Outpatient operations lower the
      financial burden of the health insurance companies, medical care services can be
      reduced.

PMID- 7571892
TI  - [Theoretical limits of "permissive anemia"].
AB  - The limiting factor for acute anemia is myocardial oxygen supply, since arterial
      oxygen content is decreased by isovolemic hemodilution while myocardial oxygen
      demand is increased as a result of a compensatory increase of cardiac output. A
      theoretical model was developed which describes the relation between hematocrit,
      myocardial oxygen demand and the required coronary blood flow during progressive
      hemodilution. Using this model, the determinants of critical hematocrit and the
      limits of intentional acute anemia (= "permissive anemia") can be calculated
      based on the limits of coronary vasodilator reserve. For a normal systemic oxygen
      consumption of 120 ml min-1 m-2 a critical degree of hemodilution is achieved at
      an hematocrit of 14% and an hemoglobin content of 4.7 g dl-1, respectively.
      Hyperoxia with an arterial pO2 of 400 mmHg will shift the critical hematocrit to
      12%. An increase of systemic oxygen consumption by a factor of three (460 ml min
      1 m-2), which might be typical for a patient during the postoperative recovery
      phase, increases the critical hematocrit to 21%. In patients with coronary artery
      disease critical hematocrit levels might be much higher. We conclude that a fixed
      critical hematocrit as a transfusion trigger is not appropriate in most patients.
      Rather the indication for blood transfusions must individually appreciate the
      specific circumstances of the patient, such as expected blood loss and required
      oxygen transport capacity reserves, hemodynamic stability, coronary artery
      disease and systemic oxygen consumption. It is suggested that the model presented
      herein might be valuable for estimation of the individual critical hematocrit in
      a particular patient.

PMID- 7571893
TI  - [An artificial liver on its way to clinical reality?].
AB  - Temporary extracorporeal liver assist devices based on liver cell cultures
      represent a promising approach for the treatment of liver failure as well as for
      perioperative care in liver surgery and transplantation. Primary hepatocytes from
      donor animals as well as human cell lines have been discussed as cell sources. A
      viable cell mass of 110-220 g (= 2.5-5 x 10(10) liver cells) has to be
      functionally active in bioreactors over a time period of several days. This cell
      number correlates to 10-20% of liver cells in an adult human liver. Neither in
      animal experiments, nor in clinical trials a complete liver replacement could yet
      be shown for cell-based bioreactors, however, beneficial effects have been
      demonstrated: partial detoxification and specific synthetic functions have been
      reported in animal experiments. Two authors have shown first preliminary clinical
      data on different cell-based liver assist devices with influences on blood
      parameters and the neurological status of treated patients. Nevertheless,
      clinical improvements also have been achieved by using non-biological support,
      like charcoal-hemoperfusion and modified hemodialysis. In order to assess the
      influence of liver support devices on better results in therapy of liver failure,
      randomized clinical trials have to be performed. Prior to this, artificial liver
      support systems have to demonstrate their biocompatibility and biosafety for
      clinical use as well as their efficacy and availability.

PMID- 7571894
TI  - [Open thrombendarterectomy of the carotid arteries with routine intraluminal
      shunt implantation, a reliable method for decreasing the risk of apoplexy-
      results of 11 years experience with 546 consecutive elective interventions].
AB  - The operative removal of haemodynamical significant carotid artery stenosis by
      endarterectomy nowadays is one of the vascular surgical standard procedures.
      Purpose of the operation is prevention of ischemic strokes. For a long-term
      prognostic advantage the patient has to take the risk of perioperative mortality
      and morbidity. While efforts are being made to minimize this risk, the question
      of optimal surgical strategy has not yet finally been solved. Since 1982 in our
      hospital all carotid endarterectomies are carried out with routine insertion of
      an intraluminal shunt. The distal intima step of the internal carotid artery is
      secured by a running suture and closure of the longitudinal arteriotomy is
      accomplished by dacron patch plasty. In this manner 546 successive operations
      have been performed under general anaesthesia until 1993. Intra- and
      postoperative mortality was 0.9% with an ischemic cerebral infarction rate of
      1.8%. According to the preoperative stage of cerebrovascular insufficiency the
      frequencies for mortality and perioperative ischemic stroke were 0.6% and 1.3%
      for CVI I, 0.4% and 0.7% for CVI II and 2.8% and 5.7% for CVI IV. Apart from
      perioperative mortality for patients with CVI IV, these complication rates are
      clearly below the suggested limits of the Ad hoc Committee on Carotid Surgery
      Standards by the Stroke Council of the American Heart Association. Routine use of
      a temporary, intraluminal shunt in carotid artery operations therefore can be
      considered as a safe measure, with complication rates still not underbid by those
      achieved with intraoperative cerebral monitoring and selective shunting.

PMID- 7571895
TI  - [Prevention and therapy of prosthesis infections in the thoracic area].
AB  - Infections of vascular prostheses following replacement of the thoracic aorta
      remain a rare complication, fortunately. The incidence of prosthetic infection
      amounts to approximately 1.6%, however, there is only limited information from
      single center studies, and linearized actuarial data for more exact estimations
      are not available. Experience with prophylaxis and treatment of bacterial
      endocarditis as well as data available from peripheral vascular reconstruction
      nevertheless allow the development of treatment strategies concerning this
      complication. Experimentally, there is clear evidence that pretreatment of Dacron
      grafts using the fibrin sealant-antibiotic compound results in a significant
      protection from infection, created by artificial contamination with
      staphylococcus aureus. This concept could clearly be confirmed in clinical series
      involving treatment of prosthetic valve endocarditis. Currently, the concept of
      implantation of cryopreserved human vascular allografts is studied clinically.
      Its efficiency in infected areas and following prosthetic replacement of the
      thoracic aorta has not been proven. Some preliminary results as well as studies
      on treatment for bacterial endocarditis would suggest a clear advantage of this
      strategy, however statistically significant improvements have not been published.
      Currently available data, however, appear to be sufficient to advocate
      potentially successful techniques as a prophylaxis in routine thoracic aortic
      replacement as well as for treatment in case of a vascular prosthetic infection
      following such procedures.

PMID- 7571896
TI  - [Problems in differential diagnosis and therapy of intracardiac space-occupying
      lesions--myxoma and thrombus].
AB  - The total removal of the myxoma under extracorporeal circulation from the origin
      maintains the optimal surgical treatment. Differentiation between myxoma and
      thromboses is a problem of preoperative diagnostics. Both tumors show unspecific
      symptoms. Therefore echocardiography and angiography are required as diagnostic
      tools. Between 1984 and 1991, 14 patients were cured from intracardiac tumors in
      the Clinic for Cardiovascular Surgery of the University of Leipzig. Problems in
      the sensitivity and security of the preoperative diagnostics and certain aspects
      of the surgical treatment will be discussed.

PMID- 7571897
TI  - [Surgical therapy of leiomyosarcoma of the inferior vena cava].
AB  - Leiomyosarcoma of the inferior vena cava is a rare tumor. Radical surgical
      resection is the treatment of choice. Depending on the localization of the tumor
      surgical therapy includes the local resection of the vena cava with primary
      closure and the segmental resection of the cava with prosthetic reconstruction.
      On the basis of four cases the symptomatology, diagnostic procedures, surgical
      therapy and the results of treatment of leiomyosarcoma of the inferior vena cava
      are discussed.

PMID- 7571899
TI  - [An arteriovenous fistula in an unusual site].
AB  - Arteriovenous fistulas are caused by trauma as well as iatrogenic, the latter
      especially being facilitated by the increasing frequency of invasive diagnostic
      and interventional procedures. We report the case of an arterio-venous fistula
      between the 9th arteria intercostalis and the 9th vena intercostalis caused by
      computed tomography guided small needle aspiration of a pleural tumor.

PMID- 7571900
TI  - [A retroperitoneal hydatid cyst--a rare manifestation of Echinococcus
      granulosus].
AB  - A rare case of a retroperitoneal cyst of Echinococcus granulosus in a male adult
      is presented. Due to its extension and infiltration of important anatomical
      structures the hydatid cyst could not be completely removed by operation.
      Therefore the patient was treated with albendazole for 10 months after surgery.
      The efficiency of this combined therapy was documented by CT-scan, specific blood
      tests and histopathological findings.

PMID- 7571898
TI  - [Inflammatory pseudotumors of the lung and trachea].
AB  - Inflammatory pseudotumors (synonym: plasma cell granulomas) of the lung and
      trachea are a group of non-neoplastic lesions of unknown etiology which may occur
      at any age. The complex histomorphology und proliferative capacity of these
      pseudotumors may result in diagnostic difficulties during intraoperative frozen
      section analysis. Four cases of inflammatory pseudotumors of the respiratory
      tract (three pulmonal, one tracheal pseudotumors) are reported. One patient (16
      years, female) suffered from sudden chest pain with dyspnoe, caused by
      obstruction of the right main bronchus due to an intraluminal pseudotumor.
      Because of the intraoperative diagnosis of a malignant histiocytoma, sleeve
      resection of the right main bronchus with bronchotracheal anastomosis was
      performed. Eight years postoperative, the patient is still disease-free. Another
      patient (52 years, male) developed multiple inflammatory pseudotumors in both
      lungs with direct infiltration of the mediastinum. After three thoracotomies,
      there is still residual disease in the mediastinum. The third patient (52 years,
      male) developed an inflammatory pseudotumor in the right upper lobe after
      irradiation therapy for hypopharyngeal carcinoma several years before. The last
      case in this series is a patient (43 years, male) with suspected bronchial
      carcinoma in the left lower lobe. The intraoperative frozen section analysis
      interpreted this lesion as an bronchioloalveolar carcinoma, but the diagnosis was
      corrected in the paraffin embedded specimens. Clinical presentation, size and
      number of these tumors are very variable. Despite their rarity, inflammatory
      pseudotumors should be considered in the differential diagnosis.

PMID- 7571901
TI  - [Current aspects of premature labor].
AB  - Six to eight percent of all newborns are born prematurely. Preterm delivery
      remains the most severe event regarding morbidity and mortality of the premature
      infants. The most serious complications in the treatment of prematurity are
      intracerebral bleedings that lead to progressive hydrocephalus and neurological
      handicaps in those newborns who survive. To our knowledge, about 50% of premature
      births with cerebral bleedings of stage I-II show normal or slightly decreased
      postnatal development. Both, a sufficient oxygen utilisation and a regulation of
      cerebral blood perfusion are necessary to prevent periventricular leucomalacia
      and cerebral bleedings with impairment of parenchymatous tissue. Endothelial
      swellings with decreasing blood flow into the cerebral parenchyma were found only
      in cases of prolonged oxygen deficiency. Vasoconstriction may produce a circulus
      vitiosus. However, it is important to know that more than 50% of the premature
      infants probably suffer from initial cerebral bleedings already in the prenatal
      stage. During the last 10 years the infectious pathogenesis has resulted in
      better understanding of pathophysiologic factors for prematurity. The local
      cervical activation of interleukins (IL 1, 6, 8) caused by cervical infections
      stimulate the prostaglandin synthesis and cervical maturity.

PMID- 7571902
TI  - [Development of gynecologic endoscopy in Germany--a statistical overview 1989 to
      1993].
AB  - The first statistical report on pelvioscopy/laparoscopy of total Germany covers a
      five years period from 1989, 01.01 to 1993 31.12. It includes a total of 461,568
      pelvioscopies/laparoscopies from 374 hospitals and 52,861
      pelvioscopies/laparoscopies from 116 medical practitioners. Hospitals' response
      rate was 43% with 99.2% reporting pelvioscopy/laparoscopy. The response rate of
      medical practitioners was 41% with 97.4% performing same methods. During the five
      year period of survey, hospitals reported a total of 2095 serious complications
      requiring laparotomy or control laparoscopy (complication rate = 4.5/1000).
      Medical practitioners reported a total of 197 serious complications (complication
      rate = 3.7/1000). Compared with the data of the fourth statistical survey of
      laparoscopy (1986 to 1988) there is a remarkable increase in serious
      complications. Most of them are mechanical lesions of blood vessels in the
      abdominal wall or in the mesosalpinx, followed by mechanical lesions of the
      intestine. Also remarkable is the observation that pelvioscopy/laparoscopy as
      surgical method is continuously increasing. As shown in previous statistics on
      pelvioscopy for tubal sterilization the bipolar technique is the most popular one
      for both hospitals and medical practitioners. It is followed by endocoagulation
      after Semm whereas mechanical techniques are of little importance. The monopolar
      high frequency current is still used in 9.6% by hospitals and 8.8% by medical
      practitioners, with and without transsection. Sterilization failure rate remains
      nearly at the same levels as it was reported previously: 1.6/1000 in hospitals
      and 3.7/1000 in private practices. The highest failure rate was observed after
      the use of monopolar HF-techniques. 82.5% of the hospitals and 65% of the medical
      practitioners reported tendency in performing endoscopy by surgery is
      continuously increasing.

PMID- 7571903
TI  - [Pelviscopic salpingostomy with everted suture].
AB  - From 1987 to 1990 pelvioscopic distal salpingostomy was performed in 47 patients
      at the University Hospital of Kiel. The tubal mucosa was everted and fixed with
      4/0 PDS sutures. 35 patients (74%) responded to a questionnaire 2-4 years after
      surgery. A bilateral salpingostomy had been performed in 16 of these 35 cases,
      while the contralateral tube was either absent or intramurally occluded in 19
      cases. Eight patients (23%) postoperatively had an intrauterine pregnancy, five
      patients gave birth to a healthy child, one patient was pregnant at time of
      follow-up. Three patients had abortions and three experienced a tubal pregnancy
      of one or both sides. Compared to the endoscopic procedure with the CO2 laser
      pelvioscopic salpingostomy with an everted suture represents an equally suited
      alternative.

PMID- 7571904
TI  - [Abnormal glucose tolerance and insulin resistance after diabetes in pregnancy].
AB  - Women with the diagnosis of gestational diabetes mellitus (GDM) are at a greater
      risk for developing diabetes in later life. This raises the question in which
      time span, to what extent and on which pathophysiological basis disorders of
      carbohydrate metabolism are to be expected post partum. Therefore 28 former
      gestational diabetes patients (GDM) were compared to 35 control patients, who had
      shown no irregularities in the oral glucose tolerance test during pregnancy. The
      follow-up study took place 5 years after the screening during pregnancy. The
      Wilcoxon Test for random samples revealed significantly higher blood sugar levels
      in the GDM group compared to the control group at 0.1 h and 2 h (median: 0 h 96
      mg % vs 91 mg %; 1 h 155 mg % vs 126 mg %; 2 h 117 mg % vs 105 mg %; p < 0,05).
      Whereas no differences were apparent for fasting insulin, the values of the GDM
      group showed a markedly higher insulin level (Wilcoxon Test: p < 0.05) after 1 h
      (median: 74 microU/ml vs 56 microU/ml), 2 h (median: 60 microU/ml vs 38
      microU/ml) and 3 h (median: 50 microU/ml vs 33 microU/ml). The serum level of C
      peptide responded accordingly 2 h (median: 6.7 ng/ml vs 5.4 ng/ml; p = 0.04) and
      3 h (median: 5.9 ng/ml vs 4.9 ng/ml; p = 0.04) after an oral glucose
      load.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7571906
TI  - [Bacteriological findings in patients with cervical intra-epithelial neoplasia].
AB  - In order to evaluate the cervical flora in patients with histologically confirmed
      cervical intraepithelial neoplasia (grades I to III) the microbiologic results of
      216 patients with CIN were compared with those of 100 symptom free controls.
      Gardnerella vaginalis combined with Mykoplasma spp. and Bacteroides spp. were
      found in 22% of the patients with dysplasia and in 5% of the control group. The
      difference was significant (p < 0.004). Microorganisms causing sexually
      transmitted diseases like Neisseria gonoroheae and Trichomonas vaginalis were not
      found. Chlamydia trachomatis was detected in 5% of all CIN groups. Comparing
      patients with CIN I, CIN II and CIN III, we did not notice any difference in
      their bacterial flora, wet smear or smell test. However the results of this study
      indicate that women with cervical dysplasia may have a higher prevalence of an
      altered cervical flora in comparison to controls.

PMID- 7571905
TI  - [Risk assessment for familial occurrence of breast cancer].
AB  - There is now unequivocal evidence that an estimated 5% of breast cancer cases is
      inherited in families. Inherited predisposition of cancer in these families is
      thought to be the result of a mutation in one of several highly penetrant
      autosomal dominant genes such as BRCA1 or BRCA2. The BRCA1 gene which is
      localized on chromosome 17 q was recently isolated and at about the same time
      BRCA2 was localized to chromosome 13 q. A number of other genetic mutations is
      also associated with predisposition to breast cancer but accounts for a very
      small proportion of inherited breast cancer. Many women want to know whether they
      have inherited a gene predisposing to breast cancer. Those with a family history
      of breast cancer are particularly concerned about their risk of disease.
      Currently the assessment of an individual's risk of breast cancer can be
      undertaken using prediction models based on family history and can be further
      refined when molecular genetic investigations became available. Without molecular
      characterisation the Claus tables derived from the Cancer and Steroid Hormone
      Study data set are best suited to predict breast cancer risk based on age of
      onset of affected relatives. Direct screening for mutations in breast cancer
      genes in not yet generally available. Testing for inherited susceptibility is
      currently being offered to selected families where multiple cases of breast
      and/or ovarian cancer are diagnosed at an early age (younger than 45 years) as
      part of research protocols. In these families the so-called indirect gene
      analysis for linkage of disease to BRCA1 and BRCA2 or the direct analysis of
      mutations with functional significance in the BRCA1 gene allows relatively
      refined risk assessment for non-diseased female family members. Some examples
      will be presented to illustrate risk assessment in different familial and
      individual situations. Risk assessment including test result interpretation and
      counselling can be appropriately provided directly to the patient by physicians
      and genetic counsellors in a coordinated genetic counselling setting.

PMID- 7571907
TI  - [Struma ovarii--case report of a rare ovarian tumor].
AB  - It has been reported a case of struma ovarii as an accident evidence during an
      operative classification of a great pelvic tumor. As it is reported in several
      publications we found an unilateral ovarian process. Clinical signs of
      hyperthyreosis or struma colli were missed. In case of benign pathological
      evidence treatment can be restrict to surgical tumor removal and ambulante
      observation.

PMID- 7571908
TI  - [The evolution of the synapses in the vertebrate central nervous system (a
      topical paper)].
AB  - The results of comparative morphological and ultrastructural research of the
      synaptic organization of spinal cord motoneurons from fishes, amphibian, reptiles
      and mammals are presented in the review. Fundamental regularities of the
      formation of the synaptic organization of motoneurons in vertebrate phylogenesis
      were established. The results of electron microscopical analysis showed that all
      basic elements of the synaptic ultrastructure preserved in the motoneuronal
      synapse of vertebrates during the evolution. On the basis of large experimental
      material it was found that the synaptic organization of individual motoneuron as
      a whole underwent structural reorganization, presented as corresponding
      transformations in mechanisms of the synaptic transmission.

PMID- 7571909
TI  - [The reflex and direct actions of novocaine on the rhythm of the heart beats in
      rats in early postnatal ontogeny].
AB  - In experiments on newborn rats it was shown that heart beating frequency depended
      on the intensity of interoceptive afferentation. Partial shutdown of the
      afferentation by means of intraperitoneal injection of novocaine in the dose of
      25 mg/kg of body weight caused the increase of heart beating and the more
      complete one at higher doses (100 mg/kg of body weight) led to its decrease. The
      injection of 2% novocaine (150-200 mg/kg of body weight) into the peritoneum of
      rat puppies on the first week of life caused the transition of bradycardia into
      temporary or permanent stop of heart beating. The same effect was observed for
      isolated atrium of rat puppies on the first week of life after the addition of
      0.1% novocaine to feeding solution. This effect disappeared in older animals. It
      was concluded that resorptive effect of novocaine on heart structures causing the
      disturbance of heart automatism in newborn rats occurred along with the reflex
      one.

PMID- 7571910
TI  - [The chronic action of large doses of aluminum on nervous and cardiac activities
      in rats administered it intramuscularly].
AB  - The influence of high doses of aluminium chloride on the central nervous system
      and regulation of the heart activity in 12 rats of Wistar line (6 experimental
      and 6 control animals) at intramuscular injection during 10 days was studied.
      Changes in animals behaviour as well as variations in electroencephalogram (EEC)
      in the form of paroxysmal activity and the increase of capacity in beta 1.2 EEG
      spectra of sensomotor cortex and beta 2 EEG spectrum of optic cortex were
      observed within 2-3 days after daily injection of AlCl3 in the dose of 400 mg/kg.
      These changes in behaviour and EEG as well as the results of morphological and
      biochemical research obtained in other works indicated that aluminium influenced
      mainly on the central nervous system. Further accumulation of AlCl3 as the result
      of daily injection of effective dose (400 mg/kg) during the following 7-8 days
      took place without marked increase of physiological changes but led to the death
      of 50% of animals studied pointing to LD50 value for 10 days, approximately equal
      to 400 mg/kg per day (total dose was 4.0 g/kg), and the large latent period and
      cumulative nature of aluminium chloride effect. Aluminium influence on the rhythm
      of the heart activity to the point of death was not revealed pointing to relative
      stability of the peripheral nervous system to the toxic action of aluminium.

PMID- 7571911
TI  - [The composition of the blood in pups of the Baikal seal Phoca sibirica during
      forced diving].
AB  - A set of parameters, such as pO2, pCO2, the content of glucose, glycogen,
      lactate, pyruvate, cholesterol, insulin, triglycerides, cAMP in the blood from
      the venous sinus has been investigated in puppies of Baikal seals during forced
      diving and rehabilitation. The dynamics of these parameters is presented.

PMID- 7571912
TI  - [The effect of social factors on the process of learning complex forms of
      behavior in adolescent chimpanzees].
AB  - Learning behaviour in chimpanzee has been investigated on a group of three
      animals at the age of 5-6 years. Situation conditioned reflex was elaborated in
      unrestrained monkeys which were trained to visual discrimination between abstract
      images of various complexity. Changes in experimental situation significantly
      affected learning process. It was shown that social contacts with experimenter
      are important for the effective learning in juvenile chimpanzee.

PMID- 7571913
TI  - [Aging and the morphofunctional changes in the hypothalamo-hypophyseal-adrenal
      cortical system].

PMID- 7571915
TI  - [Rare forms of reflex epilepsy--the epilepsy of calculation and the epilepsy of
      eating].
AB  - The authors report rare forms of reflex epilepsies-epilepsy of calculation and
      epilepsy of eating. Diagnostic and therapeutic aspects of the pathology are
      considered in comparison with publications in the literature. Conception of
      pathogenesis of the disease is proposed.

PMID- 7571914
TI  - [A disease of unknown etiology in Cuba].

PMID- 7571917
TI  - [The systematization of epilepsy remissions].
AB  - Problems of systematization of remissions of epileptic seizures and epilepsy are
      discussed on the basis of clinical examination of 341 epileptic patients with
      seizures suppressed for many years and international classifications of epilepsy.
      A classification, developed by the authors, is presented. It reflects stages of
      regress of the disease in achievement of prolonged (for years) control of
      seizures. The possibility of drug dependence development in these therapeutic
      remissions is also taken into consideration.

PMID- 7571919
TI  - [An immunoenzyme analysis of the neurospecific proteins in the blood serum of
      epilepsy patients].
AB  - Serum levels of glyofibrillar acid protein (GFAP), alpha-2 glycoprotein (A2GP),
      alpha-1 brain globulin (A1BG), alpha-2 brain globulin (A2BG) were measured in 41
      epileptic patients (2 groups--with convulsive and non-convulsive forms of the
      disease) with the help of "sandwich" variant of enzyme immunoassay and double
      centered enzyme immunoassay on the basis of column immunosorption chromatography.
      Investigations were performed in the interval from the first to the 30th day
      after the fit. The level of at least one of neurospecific proteins was elevated
      in 65.2% of patients. The same changes were revealed in one third of patients
      during the period of 30 days. Frequency discovering of A1BG as compared to A2GP
      was significantly lower only in patients with convulsive epilepsy. It allowed the
      authors to suggest, that serum antigenic levels in patients with various forms of
      epilepsy were different.

PMID- 7571916
TI  - [Juvenile myoclonic epilepsy].
AB  - Juvenile myoclonic epilepsy (JME) is an idiopathic primary generalized epilepsy
      of teenagers, characterized by massive myoclonic seizures. 18 patients were
      investigated. Myoclonic seizures first appeared at the mean age of 14 years and
      were characterized by short rapid abrupt involuntary jerks of extremities with
      the preserved consciousness. There were 2 types of myoclonic fits: massive
      seizures with symmetric jerks of extremities (33% of patients) and asymmetric
      asynchronous seizures of various frequency and intensity (67% of patients). In
      50% of patients there were myoclonic seizures in leg muscles, in some cases
      patients fell down (myoclonic-astatic seizures). The authors emphasize the
      unusually high frequency of cases with myoclonic seizures combined with absences
      (66,7%) and generalized convulsions (83,3%) occurring on awakening. It is
      suggested that myoclonic component in the structure of absences may be an early
      sign of JME and predict development of myoclonic seizures.

PMID- 7571918
TI  - [A change in the thyroid status of children with epilepsy being treated with
      diphenylhydantoin].

PMID- 7571920
TI  - [The function of the kallikrein-kinin system of the blood serum in epilepsy
      patients during therapy].
AB  - Pronounced activation of serum kallikrein-kinin system (KKS) was discovered in
      epileptic patients. Marked therapeutic effect in 17 patients after 1 month of
      combined therapy (antioxidants and vitamins) was accompanied by a distinct
      tendency to normalization of kallikrein and prekallikrein activity and the
      quantity of immune complexes (IC). Therapy of such patients may consist of one
      course of treatment followed by supportive vitamin therapy. The increase of
      previously low kallikrein activity was noticed in 23 patients after the treatment
      and was connected with the increment of prekallikrein level in the presence of
      KKS activating factors, including IC. IC quantity increased in comparison to pre
      treatment values. This promoted continuation of the treatment till normalization
      of KKS components and IC. Absence of clinical improvement combined with
      deterioration of biochemical parameters (in 11 patients) urges the necessity to
      search for more effective therapeutic measures. Determination of kallikrein, its
      precursors and IC allows to evaluate efficacy and duration of pathogenetic
      treatment of epileptic patients.

PMID- 7571921
TI  - [Therapeutic drug monitoring and the pharmacokinetics of carbamazepine in
      children with a convulsive syndrome].
AB  - An analysis of maximal and minimal serum concentrations of carbamazepine was
      performed in 40 children with convulsive syndrome. All the patients received the
      drug for a long period. Considerable case-to-case differences of serum
      concentrations in spite of practically equal doses were revealed. Serum drug
      concentrations were therapeutically optimal (6-8 mg/ml) only in one third of
      children. On the basis of pharmacokinetic parameters, mean optimal dosages
      sufficient for maintenance of effective and safe carbamazepine concentrations
      were calculated. As the child grows general clearance of carbamazepine decreases.
      Over the age of 9 years it is significantly lower in girls than in boys of the
      same age. Speed of carbamazepine elimination was higher in cases of combined
      treatment than in cases of monotherapy. Indications and optimal time for
      therapeutic drug monitoring of carbamazepine are determined and clinical
      illustrations are presented.

PMID- 7571922
TI  - [The international classification of epilepsy and the main trends in its
      treatment].

PMID- 7571923
TI  - [Lamiktal in the treatment of epilepsy patients].
AB  - Lamictal (Lamotrigin) action was studied in 61 patients with partial and
      generalized epileptic seizures (not fewer than twice a month). Most of the
      patients received Lamictal in doses of 200-300 mg daily as well as other
      antiepileptic medications (before lamictal all patients were treated without
      effect with various antiepileptic medications). Effectiveness of treatment with
      lamictal includes: the cessation of epileptic attacks (5 patients), its more rare
      appearance (31 patients), transformation into more light fits (15 patients).
      Lamictal has a broad spectrum of antiepileptic activity: it stops generalized
      tonic-clonic seizures, absences, simple and complex partial seizures as well as
      secondarily generalized tonic-clonic seizures. The medication is also effective
      in patients with psychopathologic symptoms.

PMID- 7571924
TI  - [Adaptive biocontrol in the system of treating epilepsy patients].
AB  - Adjuvant treatment of seizures by means of adaptive bioregulation was developed
      on the basis of material comprising 53 epileptic patients. The onset of auras or
      predictors of seizures was the signal to begin self-regulating activity. Method
      of suppression of paroxysmal epileptic activity in the moment of autogenic
      submersion of the patient is described. Efficacy of autogenic submersion was
      controlled by reduction of paroxysmal activity on EEG during EEG-examination in
      the hospital. The approach proved superior to chemotherapy alone.

PMID- 7571925
TI  - [The diagnosis and treatment of a Barre-Masson tumor].
AB  - Eighteen patients with Barre-Masson's tumor were operated on. Case reports are
      presented. Recovery took place in all the patients after the operation.

PMID- 7571927
TI  - [The characteristics of the psychopathological symptoms in children with a
      residual organic brain lesion].
AB  - Basing on the evidence obtained on 120 children the author investigates such
      manifestations of organic brain lesion as pathologic fantasies and specific
      inversion of moral feeling (Max and Moritz symptom). Differential-diagnostic
      criteria are provided to distinguish Max and Moritz symptom with schizophrenia.

PMID- 7571926
TI  - [Cerebrolysin in the treatment of partial optic atrophy in children].
AB  - The purpose of the trial was to investigate efficacy of cerebrolysin in children
      with partial optic atrophy and to compare different ways of injections of the
      drug. Cerebrolysin was injected in retrobulbar space and in Tenon's space. The
      drug was given separately and in combination with trental. Favorable effect has
      been achieved in all the patients treated with cerebrolysin injections in Tenon's
      space. In patients treated with retrobulbar injections of cerebrolysin and with
      injections of cerebrolysin and trental improvement occurred in 50% of cases. In
      control group, who did not receive cerebrolysin favorable results were achieved
      in 25% of patients. A 12-month follow-up study stated stability of the effect of
      cerebrolysin.

PMID- 7571928
TI  - [The dynamics of developmental disorders of the brain in fetuses obtained from
      mothers consuming alcohol during pregnancy (14- to 15-week-old fetuses)].
AB  - By histological method cerebral development was studied in 3 fetus obtained after
      14, 14 and 15 weeks to gestation in the mothers abusing alcohol. The excessive
      plication, invagination and adhesions of the brain wall, porencephalia, abnormal
      hyperplasia and heterotopia of cells, as well as agenesis of plexus choroideus
      were detected. These finding were compared with the disturbances in 5- to 12-week
      old embryos which had been earlier discovered by authors. It was noted their
      resemblance, which means the stability of the structural brain changes during
      ontogenesis.

PMID- 7571929
TI  - [The history of the outstanding discovery in the field of physiology made by the
      neurologist I. F. Tsion].

PMID- 7571930
TI  - [G. Ia. Troshin--neurologist, psychiatrist, psychologist (on the 120th
      anniversary of his birth)].

PMID- 7571931
TI  - [The syndrome of benign intracranial hypertension].
AB  - Eighty patients with benign intracranial hypertension (BIH) (76 females, 4 males,
      age range 15-54 years) were studied. Endocrine changes (pregnancy-17, obesity-16,
      dysmenorrhea-15, hyperthyroidism-7, etc.) were the most common cause of BIH
      (72.5%-58 from 80). Besides general sings of intracranial hypertension
      (papilledema-80, headache-76, nausea-47, dizziness-43, obnubilations-39), 36
      (45%) patients had visual problems. After treatment complete recovery took place
      in 48 patients, non-significant residual changes persisted in 16 patients, main
      symptoms of BIH persisted in 16 patients. Papilledema regressed completely in 52
      patients, post-papilledematous discoloration of optic disks or optic atrophy were
      discovered in 12 patients.

PMID- 7571932
TI  - [A positive effect from a combination of gonadotropin with antiepileptic
      preparations in patients with hypogonadism and epileptic seizures].
AB  - The paper reports a case of combination of hypogonadism with epileptic fits. This
      presentation confirms the importance of endocrine factors and their probable
      influence on epileptic activity.

PMID- 7571933
TI  - [Kleptomania: some psychopathological characteristics].

PMID- 7571934
TI  - [Rolandic epilepsy].

PMID- 7571935
TI  - [Depression, antidepressants and the biological clock].

PMID- 7571936
TI  - [Exteroceptive suppression of voluntary muscular activity: a new method of
      studying central nociceptive mechanisms].

PMID- 7571937
TI  - [The practical clinical game and discussion as active teaching methods in the
      training of the future physician].

PMID- 7571938
TI  - [Apropos the article "The jumping Frenchman from the state of Maine" syndrome].

PMID- 7571939
TI  - Task- and subject-related differences in sensorimotor behavior during active
      touch.
AB  - Rats explore objects by rhythmically whisking them with their mystacial
      vibrissae. On two types of tactile discrimination tasks, macrogeometric and
      microgeometric, better performers palpated the discrimnanda for longer periods of
      time and used movement patterns that appeared to optimize whisking frequency
      bandwidth and the extent to which the vibrissae would be bent by object contact.
      On a task involving finely textured surfaces, good and poor performers differed
      in the temporal components of their whisking patterns, whereas the spatial domain
      was more important for animals palpating surfaces with widely separated features.
      These findings are consistent with increasing neurophysiological evidence that
      the central representation of the tactile periphery, in rodents and other
      mammals, is both integrative and dynamic.

PMID- 7571940
TI  - Functional properties of cells in rat trigeminal subnucleus interpolaris
      following local serotonergic deafferentation.
AB  - We have previously demonstrated increases in serotonin (5-HT) content and
      immunoreactivity within spinal trigeminal subnucleus interpolaris (SpVi) that are
      correlated with the functional changes observed in this subnucleus following
      adult infraorbital nerve (ION) transection. To assess the possible functional
      significance of this change, we have examined the influence of 5-HT afference
      upon the normal response properties of cells in SpVi. We employed local depletion
      of the transmitter, using 5,7-dihydroxtryptamine (5,7-DHT), in combination with
      extracellular single-cell recording. Chromatographic methods revealed a 97.6%
      depletion of 5-HT 24 hr after neurotoxin injection. Immunocytochemical procedures
      revealed depletion of 5-HT throughout SpVi. Physiological recordings were made
      from 403 SpVi cells in 5,7-DHT-injected rats and 387 cells in vehicle-injected
      rats. All recordings were made 19-27 hr after injection. Horseradish peroxidase
      (HRP) deposits from the recording electrode were used to mark recording tracks. 5
      HT depletion did not influence receptive field (RF) location, size, or
      continuity, or the dynamic response characteristics of SpVi cells. It did,
      however, (1) alter the probability that certain types of somatosensory receptor
      surfaces would activate local-circuit neurons, and (2) influence the rate of
      firing of spontaneously active SpVi cells. There was a significant increase in
      the proportion of vibrissa-sensitive cells with infraorbital RF components, and a
      concurrent decrease in the proportion of guard-hair-sensitive cells. It therefore
      appears that 5-HT input to SpVi is necessary for some mechanoreceptive features
      of the normal functional organization of this area. These functional changes were
      interesting in that they were opposite to those found following adult ION
      transection, which increases 5-HT within SpVi. Thus, changes in 5-HT central
      afference to SpVi that follow ION damage may be responsible for at least one type
      of functional change observed following this peripheral lesion.

PMID- 7571941
TI  - Dimensions of spatial acuity in the touch sense: changes over the life span.
AB  - Spatial acuity of the touch sense and its variation in aging came under
      psychophysical scrutiny at the fingertip and control body sites. Acuity is viewed
      as encompassing the discrimination of four features of simple stimulus
      configurations: (11) discontinuity (gaps in lines or disks), (2) locus on the
      skin, (3) length (or area), and (4) orientation (e.g., along or across the
      finger). Each of these dimensions of acuity serves uniquely in tactile
      perception, as illustrated in the structure of braille. For their measurement,
      psychophysical tests were developed and refined. These were aimed at freedom from
      bias, rapid estimation of acuity thresholds in hundreds of subjects, and eventual
      applicability to the whole body surface. Some 14 versions of the tests were
      administered in three experiments, yielding 1478 individual thresholds.
      Experiment I (15 young and 15 elderly subjects) and Experiment II (131 subjects,
      ages 18 to 87 years) shed light on the nature of discrimination of discontiniuty
      and orientation. These mainly concern pitfalls of measurement and influence of
      exact stimulus configuration. Experiment III (115 subjects, ages 8 to 86 years)
      examined refined versions of tests for all four dimensions of acuity. Four
      principal findings emerged: (1) At all ages, thresholds for the four dimensions
      of acuity differ from one another in size--in order from smallest to largest:
      length, locus, orientation, and discontinuity. Exact sizes differ for transverse
      and longitudinal stimulus alignment. (2) All four acuity dimensions deteriorate
      with age, to a first approximation manifesting a constant increase in threshold
      of approximately 1% per annum between ages 20 and 80 years. That similar rates of
      deterioration characterize all four dimensions in the fingertip suggests a common
      mechanism, possibly thinning of the same mediating receptor network. (3) Acuity
      at more central sites (forearm, lip) deteriorates more slowly than at the
      fingertip. (4) Individual differences in acuity abound, even after the effects of
      aging are discounted.

PMID- 7571943
TI  - Tonic pain evoked by pulsating heat: temporal summation mechanisms and perceptual
      qualities.
AB  - The properties of a newly developed tonic heat pain model (THPM), which makes use
      of pulsating contact heat, were investigated in 18 young men. The most important
      feature of this model is that repetitive heat pulses with an intensity of 1
      degree C above the individual pain threshold are employed. This approach was used
      to tailor the tonic pain stimulation to the individual pain sensitivity. In the
      first of two experiments, the effects of pulse frequencies ranging from 5 to 30
      pulses per minute (ppm) on ratings of pain intensity and pain unpleasantness
      (visual analogue scales) were examined. At all frequencies, both ratings
      increased steadily over the 5-min test period. Frequencies of 15 ppm or more
      appeared to enhance pain intensity throughout the test period compared to the
      lower frequencies, but did not appear to alter pain unpleasantness. This suggests
      that only pain intensity is influenced by slow temporal summation and that a sort
      of frequency threshold exists for this kind of summation. In the second
      experiment, the THPM was compared to a well-established form of tonic pain
      stimulation, the cold-pressor test (CPT); visual analogue scales were again used,
      and in addition the McGill Pain Questionnaire was employed. The CPT appeared to
      produce stronger tonic pain than the THPM. However, as is typical with tonic
      pain, both tonic pain models induced relatively higher values on the affective
      pain dimension than on the sensory pain dimension. The time course of pain was
      dynamic in the CPT, with an increase followed by a plateau phase, at least in
      those subjects who could tolerate the CPT for more than 60 sec. In contrast, as
      in the first experiment, the pain ratings in the THPM were characterized by a
      slow and steady increase over time. Moreover, there was absolutely no indication
      of a dichotomy between "pain-sensitive" and "pain-tolerant" individuals in the
      THPM, although such a dichotomy was evident in the CPT. This implies that the
      distinction between pain-sensitive and pain-tolerant individuals can be made only
      with the CPT, and that this distinction represents individual differences in
      peripheral vascular reactions to cold rather than in pain perception. In
      conclusion, the THPM appears to produce a stable and predictable temporal pattern
      of tonic pain with a predominant affective component, and to be suitable for
      application in the majority of individuals without causing undue discomfort.

PMID- 7571942
TI  - Calcitonin gene-related peptide and peripherin immunoreactivity in nerve sheaths.
AB  - The intrinsic innervation of rat sciatic nerve sheaths was studied by means of
      immunohistochemical labeling for calcitonin gene-related peptide (CGRP) and
      peripherin. CGRP immunoreactivity (CGRP-IR) and peripherin immunoreactivity
      (peripherin-IR) were found in fine nerve fibers independent of nerve sheath
      vasculature. These findings suggest that a subset of the nervi nervorum may have
      nociceptive functions, and that this subset is distinct from nerve fibers that
      innervate the blood vessels of the nerve sheaths.

PMID- 7571944
TI  - Deafferentation-induced expression of GAP-43, NCAM, and NILE in the adult rat
      dorsal horn following pronase injection of the sciatic nerve.
AB  - The expression of growth-associated protein 43 (GAP-43), neural cell adhesion
      molecule (NCAM), and nerve-growth-factor-inducible large external glycoprotein
      (NILE) in the adult rat dorsal horn was examined at several survival times after
      unilateral pronase injection of the sciatic nerve. Pronase injection produces a
      permanent major loss of sciatic primary afferents in the dorsal horn, and there
      is a later sprouting of saphenous afferents into the sciatic territory. Small
      diameter myelinated and nonmyelinated saphenous afferents sprout within the
      superficial dorsal horn, and larger, myelinated afferents sprout within the deep
      dorsal horn. In the present study, GAP-43 and NCAM immunoreactivity increased in
      the superficial dorsal horn by 10 days after injection. By 20 days, the increase
      spread into the deep dorsal horn; NCAM returned to normal after 1-2 months, but
      GAP-43 persisted up to 4 months. NILE immunoreactivity appeared in laminae I and
      II by 10 days and increased up to 30 days; by 2 months no NILE remained. NILE
      never spread into the deeper dorsal horn, regardless of survival time. These data
      suggest a correlation in the expression of both NCAM and NILE with the sprouting
      of fine-diameter sprouting afferents in laminae I and II, and of NCAM expression
      with the sprouting of larger-diameter afferents in the deep dorsal horn.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7571945
TI  - [The material isolated from bovine liver promoted the immunity of chicken].
AB  - The material isolated from adult bovine liver was proved to have the similar
      properties as chicken bursin. It promoted the immunity of chicken by increasing
      the production of antibodies and enhancing the development and differentiation of
      B lymphocytes when the material was injected into 13th and 15th days chick
      embryos. Furthermore, the present experiments revealed that the material isolated
      from adult bovine liver could strengthen chicken's defence ability against
      infectious bursal disease virus. These findings indicate that adult bovine liver
      may contain bursin-like factors.

PMID- 7571946
TI  - [The regulation of calmodulin in the cell cycle].
AB  - In order to study the role of calmodulin (CaM) in the cell cycle, RC 3 cells
      carring the CaM expression vectors which was constructed by joining the CaM cDNA
      with a plasmid of mouse mammary tumor virus (MMTV), were used in this experiment.
      The CaM expression vectors transcription is regulated by a dexamethasone (DXM)
      inducible MMTV LTR promoter. Upon addition of DXM, cells have transiently
      increased CaM mRNA and protein levels. Increased CaM caused a acceleration of
      proliferation. Flow cytometric analysis showed that progression though G1, G2 and
      metaphase was accelerated by increase in CaM levels, while treatment with the CaM
      antagonist trifluoperazine (TFP) blocked cell cycle progression at G1/S boundary
      and during G2/M and metaphase. The studies have shown that CaM is important in
      controlling progression at three points in the cell cycle: (1) The G1/S boundary
      to permit the initiation of DNA synthesis; (2) The G2/M boundary to permit the
      initiation of mitosis; (3) At the metaphase/anaphase transition of mitosis to
      permit chromosome segration and the completion of mitosis. This study indicates
      that the RC 3 cell is a useful experimental cell model for studing the effect of
      a transient increase of intracellular CaM levels on control of cell cycle.

PMID- 7571947
TI  - [The study on the mechanism of EGF inducing the in vitro meiotic maturation
      resumption of mouse oocytes].
AB  - The effect and mechanism of EGF and progesterone on the meiotic maturation
      resumption were studied. The results showed that progesterone regulated the
      action of EGF. The inhibitor of 3 beta-HSD, the key enzyme of progesterone
      synthesis, Epostane could not only prevent the effect of EGF, but inhibit the
      progesterone production promoted by EGF in cultured ovary granulosa cells as
      well. On the other hand, heparin could lessen the function of EGF and
      progesterone, which implies that calcium participated the effect of EGF and
      progesterone. Fura-2 was used to indicate the changes of intracellular calcium
      level in single cumulus cell. It is found that a calcium wave appeared in cumulus
      cell when EGF or progesterone acted. But Ca2+ level returned to normal
      immediately after progesterone was added, and Ca2+ in the cumulus cell still
      remained higher level after EGF acted. This results indicated that calcium in
      cumulus cell adjusted the action of EGF and progesterone.

PMID- 7571948
TI  - [Membrane fusion between Ehrlich ascites of mastocarcinoma cells and liposome
      induced by proton translocation of transplasma membrane NADH-ferricyanide redox
      enzymes].
AB  - By using resonance energy transfer assay (RET) and fluorescence microscopy we
      show experimental evidence that membrane fusion of Ehrlich ascites of
      mastocarcinoma cells with liposomes could be induced by the proton translocation
      activity associated with NADH-ferricyanide redox enzyme of transplasma membrane
      of cancer cells. The iodoacetate, an inhibitor of glycolysis, was found to be
      able to depress the proton translocation activity and also to inhibit the
      membrane fusion. It is suggested that NADH produced mainly by glycolysis is
      utilized as the substrate (electron donor) for transmembrane ferricyanide
      reduction, and the proton pumping activity in the cancer cells is coupled to the
      transmembrane NADH-ferricyanide redox enzyme system. Experiments also show that
      membrane fusion extent of cancer cells with liposomes is proportional to the
      amount of H+ pumped out by the cells and membrane fusion process also exhibits a
      H+ consuming mode just as in fusion process of mitochondria with liposomes by
      redox enzyme proton pumps of respiratory chain. All of the results presented in
      this paper consists with recent reports of this laboratory, which indicated that
      various types of proton pumping system from different membrane system of cell
      have a new function in membrane fusion. Therefore, the proton pumping induced
      membrane fusion may have a more general physiological importance in triggering
      and modulating fusion process of native membrane in vivo.

PMID- 7571949
TI  - [A preliminary study on early development of goat (Capra hircus) reconstituted
      embryos].
AB  - Goat reconstituted embryos (REs) have been produced by electrofusion-mediated
      nuclear transplantation method. Single cell derived from normal embryos or REs
      developed to 8-cell morula stage or the inner cell mass (ICM) of early blastocyst
      stage was used to fuse with enucleated mature egg (26-28 hrs after injection of
      LRH). According to the results summarized in table 1 and 2, we decided to adopt
      the method to embed REs in agarose and then transfer into goat oviduct lumen of
      host mother for 4-6 days in vivo culture. Normal fertilized eggs seem to develop
      synchronously, but that of REs are not. Tables 4 and 5 reveal that REs and
      embryos reconstituted successively can develop normally, no significant
      difference was found among their development rates. All these experimental
      results indicate that nuclei of some blastomeres from normal embryos or REs
      (derived from eight cells to morula or ICM) retained their totipotency for
      further development. These nuclei can be reprogrammed in host ooplasm, and
      developed to term.

PMID- 7571951
TI  - [An ultrastructural study on resting cyst of Euplotes encysticus].
AB  - For resting cysts of Euplotes encysticus, in their various ciliatures, most of
      the ciliary shafts above the cilia kinetosomes are degenerated, or preserve their
      kinetosomes only. Sometimes, kinetosomes of certain frontal and ventral cirri are
      also disintegrated and disappeared. For remaining cilia, on their shafts,
      peripheral doublet microtubule (MT) and central pair of MTs still possess their
      structural pattern of "9 + 2". In few ciliary shafts, the phenomena of 2 sets of
      "9 + 2" structures surrounded by a common sheath can also be seen. At the center
      of kinetosomal peripheral triplets (triplet MTs), aggregates of MT-like
      structures are formed. For kinetosomal accessory structures, only residues of
      inter-kinetosomal connections and ciliature brackets can be seen. No MT layers
      can be seen under the pellicles of non-ciliated cortex. At the ciliated cortex,
      there are peripheral MT layers (corresponding to sub-pellicular MT layers) within
      the ciliature cavity, MT ribbons at (and near) the deeper parts of ciliature, and
      scattered MT groups. Besides, various shapes of ciliary shafts structures are
      seen within cortical vesicles of ciliated regions. Nuclear pores of macronucleus
      enlarged apparently, reduced in number, and, chromatin attached on the inner
      membrane of these nuclear pores.

PMID- 7571950
TI  - [Cell-specific expression of AFP gene is dependent on some nuclear proteins].
AB  - AFP is an oncodevelopmental protein. Its level decreases abruptly after birth and
      reaches almost undetectable level during normal adult life. However, reexpression
      of the gene can be observed during hepatocarcinogenesis. To further understand
      mechanism of regulating AFP expression, we checked several restriction enzyme map
      of 5' terminal and flanking sequences of AFP gene. There are no differences among
      adult rat liver, fetal liver and hepatoma cells. Using +2(-)-255 bp sequence
      probe of AFP gene to do southwestern blotting assay, the result showed that the
      gene-active cells, such as hepatoma cells, contained binding-proteins which were
      apparently lacking in adult rat liver, lung, spleen, heart and kidney cells.
      While the fractions of nuclear proteins from adult rat liver cells were devoid of
      any stimulatory effect on transcription, those of binding-proteins from hepatoma
      stimulated the transcription of AFP gene in vitro. The hepatoma binding-proteins
      can rescue transcription activity of fraction of nuclear proteins from adult rat
      liver cells. These results indicate that cell-specific expression of AFP gene is
      regulated by protein-factors.

PMID- 7571953
TI  - Negative-staining, refractile mycobacteria in Romanowsky-stained smears.

PMID- 7571952
TI  - [Expression of exogenous porcine transforming growth factor beta-1 gene in ES
      cells and its effect on their differentiation in vitro].
AB  - A TGF-beta 1 gene expression plasmid was constructed by inserting the porcine 1.7
      Kb TGF-beta 1 cDNA into BamHI site of retrovirus vector Dol. The plasmid DNA was
      introduced into mouse embryonic stem cells (ES-5 line) by calcium phosphate
      mediated transfection, and transfected ES-5 cells were then selected by stepwise
      increase in G418 concentration. Finally, we obtained 21 clones that could be
      stably grown in culture medium with G418 at 500 micrograms/ml and were designated
      as ES-T cells. Dot blot and Northern analysis of total RNA and polyA+ RNA
      extracted from those ES-T cells were shown in FIg. 2 and 3, demonstrating that 6
      clones could express exogenous porcine TGF-beta 1 mRNA. The stronger hybridized
      signal in two clones (ES-T6 and ES-T 16) of them were further proved by southern
      hybridization of genomic DNA from these ES-T cells with 1.7 Kb TGF-beta 1 cDNA
      probe (Fig. 4). The product of TGF-beta 1 gene overexpression in ES-T 6 cells was
      shown in Fig. 5 and 6 by SE-LISA for TGF-beta 1 immunoreactivity to TGF-beta 1
      antibodies and biological assay for CCL/64 cell growth inhibition, respectively.
      With respect to some biological characteristics, ES-T 6 cells, like their parent
      ES-5 cells, retained their pluripotent properties and positive SSEA-1 antigen
      (Plate I, Fig. 1). ES-T6 cells were expanded and used for studies of in vitro
      differentiation. Both of ES-T 6 cells and control ES-5 cells could form a lot of
      simple aggregates and differentiate into embryoid bodies by hanging drop culture
      for 3 days in the presence of retinoic acid (RA) at 10(-9) mol/L. Then individual
      embryoid bodies were plated on gelatinized tissue culture wells. On the third day
      of further culture without RA, a large amounts of epithelial-like and round cells
      occurred around the embryoid bodies formed either from ES-T 6 cells or ES-5 cells
      (Plate I, Fig. 4). However, with further culture of embryoid bodies, only the
      cells differentiated from ES-T6 embryoid bodies could arrange themselves and
      differentiate into a lot of radially arranged tubular structures (Plate II, Fig.
      5). The frequency of tubular structures present in ES-T6 embryoid bodies were
      about 95.5%, but in ES-5 group there was only about 17.8% cases giving less
      defined tubular structures (Plate III, Fig. 8).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7571954
TI  - Collagenous spherulosis of the breast diagnosed by fine needle aspiration biopsy.

PMID- 7571955
TI  - Atrophic vaginitis and urinary symptoms in postmenopausal women.

PMID- 7571956
TI  - Full-length, live, adult filarial worm in a fine needle aspirate of an epididymal
      nodule.

PMID- 7571957
TI  - Fine needle aspiration cytology in abdominal tuberculosis.

PMID- 7571958
TI  - Fine needle aspiration cytology of primary and metastatic lesions of the adrenal
      gland. A series of 188 biopsies with radiologic correlation.
AB  - OBJECTIVE: To determine the efficacy of fine needle aspiration (FNA) in the
      diagnosis of primary and metastatic lesions of the adrenal gland in conjunction
      with the radiologic size of the lesion. STUDY DESIGN: One hundred eighty-eight
      FNA biopsies performed between 1988 and 1992 with a diagnostic rate of 86% (161
      cases) were reviewed and correlated with the radiologically (computed tomography,
      ultrasound) measured size of the lesion and follow-up. RESULTS: Eighty-one cases
      (43%) were primary adrenal lesions, and 80 (43%) were metastatic tumors. Three
      large cell lymphomas and two adrenal histoplasmoses were also noted. The most
      common primary site of metastatic tumors was the lung; these 55 cases (29%)
      included 47 adenocarcinomas and 3 small cell, 2 large cell and 3 squamous cell
      carcinomas. The other metastatic tumors were 5 melanomas, 7 renal cell carcinomas
      and 1 mixed mullerian tumor. The size of the metastatic tumors averaged 5.1 +/-
      2.5 cm (+/- SD) and ranged from 1.5 to 10 cm in greatest diameter. Benign
      cortical nodules (61 cases, 32%) were the most common primary adrenal lesion,
      followed, in decreasing frequency, by 11 cortical neoplasms/carcinomas, 5
      pheochromocytomas and 1 myelolipoma. The benign cortical nodules/adenomas
      measured an average of 2.4 +/- 0.8 cm in greatest diameter and ranged from 1 to 4
      cm. The cortical neoplasm/carcinoma sizes ranged from 4 to 12 cm. CONCLUSION:
      These data suggest that FNA in conjunction with the radiologically measured size
      of adrenal lesions is a specific and sensitive method of evaluating primary and
      metastatic lesions of the adrenal gland. It is also an important diagnostic tool
      in cancer staging, obviating open surgical procedures for many patients.

PMID- 7571959
TI  - Nucleolar organizer regions in breast cytology material.
AB  - OBJECTIVE: To evaluate the presence of nucleolar organizer regions (NORs) by the
      argyrophil NOR (AgNOR) technique on scrape cytology on breast lumps. STUDY
      DESIGN: The study group consisted of 112 breast lumps that were sent for frozen
      section and included fibrocystic disease (52 cases), fibroadenomas (15 cases) and
      carcinomas (45 cases). Scrape cytology was performed on each case, and the number
      of AgNOR dots was recorded for 50 cells and the mean value calculated. RESULTS:
      The mean AgNOR counts were statistically significantly higher in malignant
      lesions in comparison to either fibroadenomas or fibrocystic changes. CONCLUSION:
      The AgNOR technique could be of use in cytologic material as an adjunct to fine
      needle aspiration of breast lesions.

PMID- 7571960
TI  - Analysis of false results in a series of 835 fine needle aspirates of breast
      lesions.
AB  - OBJECTIVE: To analyze cases of false diagnoses from a large series to help
      increase the accuracy of fine needle aspiration of palpable breast lesions. STUDY
      DESIGN: The results of FNA of 835 palpable breast lesions were analyzed to
      determine the reasons for false positive, false negative and false suspicious
      diagnoses. RESULTS: Of the 835 aspirates, 174 were reported as positive, 549 as
      negative and 66 as suspicious or atypical but not diagnostic of malignancy. Forty
      six cases were considered unsatisfactory. Tissue was available for comparison in
      286 cases. The cytologic diagnoses in these cases were reported as follows:
      positive, 125 (43.7%); suspicious, 33 (11.5%); atypical, 18 (6.2%); negative, 92
      (32%); and unsatisfactory, 18 (6.2%). There was one false positive diagnosis,
      yielding a false positive rate of 0.8%. This lesion was a case of fibrocystic
      change with hyperplasia, focal fat necrosis and reparative atypia. There were 14
      false negative cases, resulting in a false negative rate of 13.2%. Nearly all
      these cases were sampling errors and included infiltrating ductal carcinomas (9),
      ductal carcinomas in situ (2), infiltrating lobular carcinomas (2) and tubular
      carcinoma (1). Most of the suspicious and atypical lesions proved to be
      carcinomas (35/50). The remainder were fibroadenomas (6), fibrocystic change (4),
      gynecomastia (2), adenosis (2) and granulomatous mastitis (1). CONCLUSION: A
      positive diagnosis of malignancy by FNA is reliable in establishing the diagnosis
      and planning the treatment of breast cancer. The false-positive rate is very low,
      with only a single case reported in 835 aspirates. Most false negatives are due
      to sampling and not to interpretive difficulties. The category "suspicious but
      not diagnostic of malignancy" serves a useful purpose in management of patients
      with breast lumps.

PMID- 7571961
TI  - Cytologic diagnosis of ductal versus lobular carcinoma of the breast.
AB  - OBJECTIVE: To determine the value of cytology in the differential diagnosis of
      ductal versus lobular carcinoma of the breast. STUDY DESIGN: In this study we
      examined 11 cytologic parameters in fine needle aspiration (FNA) cytology
      specimens from 52 patients who underwent surgery and had subsequent histologic
      diagnoses. Eighty-eight percent (46 cases) were infiltrating ductal carcinoma,
      and 12% (6 cases) were invasive lobular carcinoma. RESULTS: Of the 11 cytologic
      parameters only chromatin pattern (P < .0001), nuclear size (P < .004) and
      overall cell size (P < .004) showed statistically significant differences between
      the two groups. Nuclear chromatin was coarsely granular only in cases of ductal
      carcinoma, while fine granularity could be seen in both ductal and lobular
      tumors. An automated morphometric system was used to determine the nuclear and
      overall cell size. The granularity of nuclear chromatin in ductal carcinoma cells
      did not correlate significantly with nuclear and overall cell size; therefore,
      they should be considered independent cytologic parameters. CONCLUSION: The
      cytologic differential diagnosis of ductal versus lobular carcinoma is difficult;
      based on this study, the presence of coarsely granular chromatin, nuclear size >
      44 microns2 and cell size > 82 microns2 are the only features diagnostic of
      ductal versus lobular carcinoma.

PMID- 7571962
TI  - Fine needle aspiration cytology diagnosis of male breast lesions. A study of 185
      cases.
AB  - OBJECTIVE: To study the fine needle aspiration (FNA) cytologic features of male
      breast lesions and to determine the efficacy of FNA cytology in the diagnosis of
      these lesions. STUDY DESIGN: During a five-year period (July 1988-June 1993), 188
      males with breast lesions were investigated by fine needle aspiration cytology
      (FNAC). Slides were available for review in 185 of these cases. RESULTS:
      Gynecomastia was the most common lesion (132 cases), followed by benign tumors
      and cysts (16 cases), carcinoma (6 cases) and inflammatory lesions (5 cases). In
      26 cases the smears were considered inadequate. The cytologic features of
      gynecomastia included cohesive sheets of bland cells (100.0% of cases), bipolar
      bare nuclei (76.5%) and columnar cells (38.6%). Mild nuclear atypia was observed
      in seven cases. The cytologic features consisted of dyshesive groups of ductular
      cells with moderate to severe nuclear atypia and absence of bare nuclei as well
      as columnar cells. The benign tumors and cysts included lipomatous lesions (10
      cases), spindle cell tumors (3 cases) and epidermal inclusion/pilar cysts (3
      cases). Histology was done in 25 cases. Diagnostic accuracy of FNAC for
      gynecomastia, benign tumors and malignancy was 100.0%, 100.0% and 66.7%,
      respectively. The only discrepant case was a carcinoma, diagnosed as highly
      suspicious on the cytologic specimen.

PMID- 7571963
TI  - Assessment of fine needle aspiration cytology and histopathology for diagnosing
      male breast masses.
AB  - OBJECTIVE: To investigate the diagnostic accuracy of fine needle aspiration
      cytology (FNAC) from breast lesions in males and to determine the frequency of
      benign versus malignant histopathologic diagnoses in surgical biopsies from male
      breast lesions. STUDY DESIGN: FNAC specimens from breast lesions taken from 241
      males over 8.5 years were divided into four subgroups according to the original
      cytologic diagnoses. Diagnostic accuracy was verified with the Norwegian Cancer
      Registry. Ten years' worth of material from 809 surgical biopsies from male
      breast lesions was subgrouped according to the original histopathologic
      diagnoses. RESULTS: Of the 809 surgical biopsies, 779 (96.3%) were benign
      lesions. Of the 241 fine needle aspirates, 27 (11.2%) were unsatisfactory for
      cytologic diagnosis. Of the remaining 214 cases, 200 benign cytologic diagnoses
      were confirmed at follow-up. Thus, there were no false negative cytologic
      diagnoses; eight malignant diagnoses were confirmed by later histopathologic
      examination of the surgical biopsy. CONCLUSION: To reduce the high rate of
      surgical biopsies of benign male breast masses, we conclude that FNAC should be
      performed as a standard procedure in the clinical evaluation of male breast
      lesions.

PMID- 7571964
TI  - Neoplastic or nonneoplastic ovarian cyst? The role of cytology.
AB  - OBJECTIVE: To improve the discrimination between neoplastic and functional cysts
      of the ovary in order to avoid superfluous surgery. STUDY DESIGN: Clinical
      examination, including ultrasound and laparoscopy, was performed on 347 women
      admitted to the hospital with ovarian cysts. In addition, we evaluated the
      contents of the cysts cytologically as well as by determining the estradiol level
      in the fluid via radioimmunoassay. RESULTS: No single method was able to offer
      definitive diagnoses distinguishing between neoplastic and nonneoplastic cysts.
      All methods were subject to a relatively high rate of false negative findings
      indicating a neoplasm. To some extent, however, they were complementary. Within
      our three-parameter scheme, hormonal analysis yielded the best results. Cytology
      had drawbacks with simple serous cystomas due to the scanty and degenerated cell
      material. However, in proliferating cases, carcinomas and mucinous cystomas,
      cytology renders nearly no false negative diagnoses. CONCLUSION: In cases of a
      three-parameter indication of a neoplasm, the diagnosis may be taken as
      definitive, and surgery should be performed. In the case of contradictory
      diagnoses, surgical intervention is required on a precautionary basis. In
      approximately 15% of cases a nonneoplastic cyst will be removed unnecessarily. In
      the case of a three-parameter negative indication of a neoplasm, an expectant
      attitude is acceptable.

PMID- 7571965
TI  - Pituitary adenomas. Correlation of the cytologic appearance with biologic
      behavior.
AB  - OBJECTIVE: To determine the extent of nuclear pleomorphism in pituitary adenomas
      and the relationship of these cytologic changes to clinical features, endocrine
      evaluations and proliferative potential. STUDY DESIGN: The study group consisted
      of 93 sequential patients with pituitary adenomas in which smear and touch
      preparations were performed. Nuclear pleomorphism was assessed semiquantitatively
      and compared to immunohistochemical analyses of pituitary hormones on formalin
      fixed paraffin sections, endocrine evaluations, clinical observations and
      proliferative potential as determined by immunoreactivity to Ki-67 on frozen
      sections. RESULTS: Varying degrees of nuclear pleomorphism were observed in 66/93
      tumors. However, these changes were more pronounced in clinically functioning
      (growth hormone, prolactin or ACTH), as compared to nonfunctioning, tumors (P <
      .01). Pleomorphism did not correlate with macroscopic invasiveness. The pituitary
      adenomas that showed pleomorphism had significantly higher Ki-67 indices than did
      those without nuclear changes (P < .02). Significantly higher Ki-67 expression
      was also found in clinically functioning tumors when compared to nonfunctioning
      tumors (P < .03). CONCLUSION: Significant nuclear pleomorphism is common in
      functional pituitary adenomas of several types but does not correlate with more
      aggressive behavior.

PMID- 7571966
TI  - Effusion cytology of hepatocellular carcinoma.
AB  - OBJECTIVE: To evaluate effusion cytology on routine smears in patients with
      hepatocellular carcinoma. STUDY DESIGN: Filed smears from 106 patients with
      autopsy-proven hepatocellular carcinoma were retrospectively reviewed for the
      presence of malignant cells. Morphologic patterns, as well as immunochemical
      reactivity for a panel of antibodies, were analyzed when feasible. RESULTS:
      Malignant cells were identified in 10 cases of ascites and 1 of pleural fluid.
      Positive smears were variably cellular, with paucicellular, round or linear
      aggregates of polygonal cells. The cytoplasm was usually evident and very
      stainable. The nuclei were hyperchromatic or vesicular, with inconspicuous
      nucleoli. Reactive changes were frequent. Malignant cells were positive for
      keratins (7/8) and erythropoietin (4/8) and negative for carcinoembryonic antigen
      (0/8). Concomitant cirrhosis was present in 103 cases (97.1%); all the
      noncirrhotic cases had malignant cells identifiable in the effusion. Antemortem
      clinical diagnosis of malignancy was made in 59 cases (55.7%); cytology was the
      only source of the morphologic diagnosis in most of them. CONCLUSION: These
      results indicate that although the yield of hepatocellular carcinoma in effusion
      cytology is limited, it may be important in the initial assessment of the
      disease, given the ineligibility of most patients for invasive procedures and the
      equivocal features of instrumental investigations. Immunocytochemistry may
      further assist in differentiating doubtful cases.

PMID- 7571967
TI  - Role of fine needle aspiration cytology as the initial modality in the
      investigation of thyroid lesions.
AB  - OBJECTIVE: To study the utility of fine needle aspiration (FNA) cytology as the
      initial modality in the investigation of thyroid lesions. STUDY DESIGN: Fine
      needle aspiration biopsies performed on patients presenting with diffuse or
      nodular thyroid enlargement and solitary thyroid nodules at the Goa Medical
      College Hospitals, Bambolim Goa, India, from January 1986 to June 1993, were
      reviewed. Two thousand four biopsies were performed on 1,992 patients, with 12
      patients undergoing repeat FNA biopsy at different times due to an inconclusive
      primary result. These repeat biopsies were also inconclusive and were excluded
      from the series, leaving 1,992 cases. Two hundred thirty-eight of these 1,992
      cases underwent surgery, either excision of the nodule or some form of
      thyroidectomy for a cytologically suspicious diagnosis, compression symptoms or
      cosmetic reasons, and a cytohistopathologic correlation was established in these
      cases. Twenty-five of the 238 cases that had inadequate cytologic findings were
      excluded, and the accuracy was studied in the remaining 213 cases. RESULTS: The
      results of FNA classified 1,557 (78.16%) of these cases as benign, 151 (7.58%) as
      suspicious, 30 (1.51%) as malignant and 254 (12.75%) as unsatisfactory.
      Cytohistopathologic correlation was established in 238 cases, which were operated
      on. Nine (5.5%) of 163 cases with an FNA diagnosis of benign, 10 (26.3%) of 38
      cases with an FNA diagnosis of suspicious and 11 (91.67%) of 12 cases with an FNA
      diagnosis of malignant were histologically malignant. CONCLUSION: FNA biopsy of
      the thyroid can be used effectively as the initial modality in the evaluation of
      thyroid lesions, both nodular and diffuse. It is very useful in detecting
      neoplastic foci in multinodular goiter and also in evaluating solitary thyroid
      nodules.

PMID- 7571968
TI  - Spectrum of cytologic changes in pregnancy. A review of 100 abnormal
      cervicovaginal smears, with emphasis on diagnostic pitfalls.
AB  - OBJECTIVE: To review pregnancy-related changes in cervicovaginal smears and to
      distinguish them from neoplasia and dysplasia. STUDY DESIGN: One hundred
      consecutive abnormal cervicovaginal smears from pregnant women obtained during
      1992-1993 were reviewed. Corresponding biopsies that were available were also
      reviewed for cytologic correlation. RESULTS: Sixty-one percent of cases showed
      inflammation changes, 21% contained low grade squamous intraepithelial lesion,
      and 9% had high grade squamous intraepithelial lesion. Diagnostic problems were
      encountered with decidual cells, Arias-Stella reaction and trophoblastic cells.
      CONCLUSION: Both the clinician and pathologist must be aware of diagnostic
      pitfalls and false positive diagnoses in pregnancy. Hence, it is extremely
      important that the clinician notify the pathologist about the pregnancy status of
      the patient.

PMID- 7571969
TI  - Diagnosis of mantle cell lymphoma on tissue acquired by fine needle aspiration in
      conjunction with immunocytochemistry and cytokinetic studies. Possibilities and
      limitations.
AB  - OBJECTIVE: To investigate the cytokinetic features of mantle cell lymphoma (MCL)
      and determine if there are measurable differences between mantle zone (MCL-MZ)
      and diffuse (MCL-D) types of MCL. STUDY DESIGN: Forty-five fine needle aspirates
      (FNAs) from 36 patients with MCL were reviewed. Immunohistochemistry, using a
      panel of kappa, lambda, CD5 and CD3, was applied in all cases. Ki-67 positivity
      using digital image analysis was measured in 29 cases. Flow cytometric analysis
      was performed on 40 specimens with DNA and RNA indices, and S + G2M phase was
      assessed. RESULTS: The great majority of cases (42 cases, 94%) were positive for
      CD5. There was a predominance of lambda-positive cases (lambda:kappa 2:1). MCL-D
      had higher mean Ki-67 values as compared to MCL-MZ (14.4% vs. 6.5%), but the
      differences were not statistically significant (P = .07). The majority of cases
      were diploid (35, 87%). MCL-D had significantly higher mean values for RNA index
      (P = .005). There was no significant difference in percentage of S + G2M between
      MCL-MZ and MCL-D; however, the diffuse type had higher mean values as compared to
      the mantle zone type (5.4 vs. 3.7). CONCLUSION: Tissue obtained by FNA is
      adequate for a diagnosis of MCL. However, while certain proliferation and RNA
      markers did show a trend toward being lower in MCL-MZ, differentiation between
      MCL-MZ and MCL-D cannot be made based on these alone; histologic architecture is
      necessary.

PMID- 7571970
TI  - Cytologic brushing as a simple and rapid method in the diagnosis of Helicobacter
      pylori infection.
AB  - OBJECTIVE: To assess broad antral cytologic brushing as an alternative approach
      for the diagnosis of Helicobacter pylori gastric colonization as compared to
      histology. STUDY DESIGN: Multiple gastric biopsies were taken from the antrum of
      117 patients with an endoscopic appearance compatible with antral gastritis.
      Broad antral brushing was also obtained, and smears were stained with
      Papanicolaou stain. RESULTS: Chronic gastritis was diagnosed histopathologically
      in 93 patients. H pylori was identified in 115 cytologic smears. Cytologic smears
      from 97 patients with H pylori on biopsy specimens contained the organisms. Only
      two poor-quality cytologic smears with no H pylori had the organisms on biopsy
      specimens. In 18 patients, H pylori was identified on the cytologic smears and
      not on the biopsy specimens. CONCLUSION: Broad antral cytologic brushing is a
      useful alternative approach to histology for the diagnosis of H pylori gastric
      infection.

PMID- 7571972
TI  - Rhinosporodiosis. Diagnosis by scrape cytology.
AB  - OBJECTIVE: To determine the utility of the simple technique of scrape cytology
      for obtaining a morphologic diagnosis of Rhinosporodium seeberi. STUDY DESIGN:
      The study included nine patients presenting with a nasal polyp alone and one
      patient presenting with a skin ulcer with a recurrent nasal polyp. Scrape smears
      from all 10 nasal polyps and skin ulcers were collected. Periodic acid-Schiff
      (PAS) stain was used on smears from three cases. Histopathology of all the nasal
      polyps and the excised skin ulcer was done. RESULTS: The scrape smears showed
      characteristic spores of R seeberi mixed with an acute and chronic inflammatory
      exudate and metaplastic cells. PAS stain showed positivity for the capsule.
      Histopathology confirmed the cytologic diagnosis. CONCLUSION: Since mature
      sporangia rupture either on the surface or within the mucosa of polyps, scrape
      smears reliably and safely retrieve abundant spores. Therefore, this technique,
      offers immense potential for a rapid and correct preoperative diagnosis of
      rhinosporodiosis. It thereby facilitates the planning of surgical interventions
      to prevent recurrences.

PMID- 7571971
TI  - Fine needle aspiration of medullary carcinoma of the thyroid. Cytomorphology,
      immunocytochemistry and electron microscopy.
AB  - OBJECTIVE: To analyze of medullary carcinoma of the thyroid (MCT) diagnosed by
      fine needle aspiration (FNA) utilizing cytomorphologic features and ancillary
      studies. STUDY DESIGN: Nine cases of MCT were collected, and the cytomorphologic
      findings were reviewed. Additionally, immunocytochemistry, immunoelectron
      microscopy and ultrastructural examination results were reviewed for selected
      cases. RESULTS: In five cases, loose groups predominated over single cells,
      whereas single cells predominated in three cases. One case showed only highly
      cohesive groups of cells. Most cells were round to oval, and every case had some
      degree of plasmacytoid morphology. Spindle-shaped cells were predominant in one
      case and were occasionally noted as a subpopulation in the other cases.
      Binucleation was noted in seven cases, and scattered, abnormally large nuclei
      were identified in five cases. The cytoplasm was moderate to abundant and
      delicate in all cases. Routine immunocytochemical staining for calcitonin and
      chromogranin was positive in three of four cases, and staining positive for the
      markers was detected by immunoelectron microscopy in two cases. In four cases,
      electron microscopy revealed neurosecretory granules. CONCLUSION: The
      cytomorphologic appearance of medullary thyroid carcinoma is highly distinctive,
      and the diagnosis can be corroborated by appropriate ancillary studies.

PMID- 7571973
TI  - Cytologic diagnosis of yolk sac tumor. A report of seven cases.
AB  - BACKGROUND: Yolk sac tumor (YST) is a rare neoplasm that affects children and
      adolescents. CASES: Fine needle aspiration biopsies from seven patients with YSTs
      were reviewed. Eosinophilic hyaline cytoplasmic bodies and irregular deposits of
      basement membrane-like material were easily recognizable in aspiration smears.
      Some of the tumor cells contained cytoplasmic vacuoles. These features correlated
      well with histologic appearances. CONCLUSION: These findings are significant in
      the fine needle aspiration biopsy diagnosis of YST. A preliminary cytologic
      diagnosis of this tumor is valuable as a guide in planning further diagnostic
      studies and therapy.

PMID- 7571974
TI  - Fine needle aspiration diagnosis of carcinoma arising in an ectopic breast. A
      case report.
AB  - BACKGROUND: Ectopic breast tissue has been found at many anatomic locations.
      Neoplastic and hyperplastic lesions similar to those that develop in the normal
      breast can occur in supernumerary ones. CASE: A 45-year-old female presented with
      a 30-cm, firm, subcutaneous mass in the left side of the chest wall that was
      clinically considered an ectopic breast. Fine needle aspiration biopsy showed
      irregular clusters and single epithelial cells with marked atypia, pleomorphism
      and occasional magenta bodies. CONCLUSION: This case illustrates that fine needle
      aspiration biopsy is a rapid and highly specific technique that can be used as
      the first diagnostic step in cases of carcinoma arising in an ectopic breast.

PMID- 7571975
TI  - Fine needle aspiration cytology of renal and retroperitoneal angiomyolipoma.
      Report of two cases with cytologic findings and clinicopathologic pitfalls in
      diagnosis.
AB  - BACKGROUND: Angiomyolipoma is a benign soft tissue neoplasm that usually arises
      in the kidney, although rare extrarenal examples have been documented. CASES: Two
      cases of the neoplasm occurred in which fine needle aspiration (FNA) biopsies
      were performed. The first patient was a 73-year-old female with a history of
      breast carcinoma who presented with a large retroperitoneal mass. Transabdominal
      FNA biopsy revealed multiple fragments of spindle-shaped mesenchymal cells, a few
      of which showed marked cellular atypia with occasional cells containing fat
      vacuoles, producing a lipoblastlike appearance. However, the atypical spindle
      cells were immunohistochemically reactive for actin, raising the possibility of a
      smooth muscle tumor rather than a liposarcoma. The surgically resected specimen
      revealed an extrarenal, retroperitoneal angiomyolipoma. The second patient was a
      71-year-old female who presented with a right renal mass and hepatomegaly.
      Computed tomography showed a mass in the upper pole of the kidney and multiple
      enhancing lesions in the liver. FNA biopsy was diagnostic of angiomyolipoma,
      which was confirmed histologically. CONCLUSION: Angiomyolipoma should be
      considered in aspirates of both renal and extrarenal masses when an admixture of
      blood vessels, fat and smooth muscle cells is encountered. Pitfalls leading to an
      incorrect diagnosis include aspiration at unusual sites for angiomyolipoma and/or
      the presence of atypical spindle cells and lipoblastlike cells, which can be
      mistaken for leiomyosarcoma or liposarcoma cells. Ancillary studies, such as
      immunocytochemistry for smooth muscle markers, may be helpful in making the
      correct diagnosis.

PMID- 7571976
TI  - Alveolar soft part sarcoma. Report of a case diagnosed by needle aspiration
      cytology and electron microscopy.
AB  - BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare tumor, accounting for
      less than 1% of all primary soft tissue malignant neoplasms. The tumor is a
      distinct clinicopathologic entity, but its histogenesis is controversial. CASE:
      The needle aspirate from a soft tissue tumor in a 15-year-old girl was stained
      with Diff-Quik and periodic acid--Schiff (PAS) with and without prior digestion
      with diastase. Minute tumor tissue fragments were processed for transmission
      electron microscopic examination (EM). Clustered malignant cells with ill
      defined, frothy or vacuolated cytoplasm showed a positive reaction with PAS and
      PAS with prior diastase digestion and oval nuclei containing macronucleoli.
      Intracytoplasmic, membrane-bound, rhomboid and rod-shaped crystals with a regular
      lattice pattern with 50-80 A periodicity were detected by EM study of aspirated
      tumor cells. CONCLUSION: Light and EM studies of aspirated tumor cells showed
      diagnostic features of the tumor.

PMID- 7571977
TI  - Diagnosis of primary cardiac lymphoma. Report of a case with cytologic
      examination of pericardial fluid and imprints of transvenously biopsied
      intracardiac tissue.
AB  - BACKGROUND: Primary cardiac lymphoma (PCL) is a treatable disease when
      appropriately diagnosed. Therefore, a prompt, safe method with high diagnostic
      accuracy is prerequisite to successful therapy for PCL. CASE: A 57-year-old male
      presented with exertional dyspnea and atrial fibrillations. A pericardial
      effusion (PE) and several tumor masses occupying both atria were found. Cytologic
      examinations of PE and of imprints of the tissues obtained by transvenous biopsy
      of the cardiac tumors revealed numerous small, round tumor cells and
      lymphoglandular bodies, suggestive of malignant lymphoma. This cytologic
      impression was confirmed by immunocytochemical studies on the same cytologic
      material. Histologic studies reaffirmed the diagnosis of B-cell lymphoma. The
      patient received eight courses of chemotherapy, with complete remission of the
      illness. CONCLUSION: Cardiac lymphoma can be quickly and safely diagnosed by
      cytologic examination of PE or transvenously biopsied cardiac tissue, with
      confirmation by immunocytochemical studies. Exploratory thoracotomy for biopsy
      can be avoided.

PMID- 7571978
TI  - Use of genetic markers during endoscopic screening and follow-up of
      gastrointestinal precancerous lesions.
AB  - A variety of premalignant lesions, including Barrett's esophagus, colonic polyps,
      ulcerative colitis, primary sclerosing cholangitis, intraductal mucin secreting
      papillomatosis are now well recognized and accessible to direct endoscopic
      assessment and biopsy or brushing. This review emphasizes the potential
      usefulness of genetic markers, in particular Ki-ras oncogene and p53 tumor
      suppressor gene mutations, in the endoscopic surveillance of these premalignant
      conditions. The adjunction of Ki-ras and p53 assays in material collected during
      endoscopic procedures may help the clinician detect earlier and with a higher
      accuracy neoplastic progression.

PMID- 7571980
TI  - How effective is enteroscopy?
AB  - The small bowel can be successfully investigated by enteroscopy techniques.
      Several types of enteroscopes with different technical characteristics have been
      developed. In this paper we explain the respective advantages and disadvantages
      of the different techniques. Results of several series using these two
      enteroscopes are summarized and commented. The review of different series make
      clear that enteroscopes, especially those including an operating channel
      represent an attractive alternative diagnostic tool to angiography and small
      bowel barium studies in patients presenting obscure digestive bleeding. The
      series reviewed in this paper confirm the high diagnostic efficacy of this type
      of endoscopy. Most of the lesions found are arteriovenous malformations
      especially in the elderly. Small bowel tumours are more likely to be found in
      younger patients. New indications for enteroscopy should be evaluated carefully.
      Obscure digestive bleeding represents the main indication of enteroscopy. However
      clinical situations suggesting Crohn's disease or malabsorption syndromes may be
      effectively evaluated by this special endoscopic technique.

PMID- 7571979
TI  - Gastric carcinoma: the Helicobacter pylori trail.
AB  - Gastric carcinoma is the world's overall second most common cancer. Besides
      obvious environmental factors, recent epidemiological studies and a better
      knowledge of Helicobacter Pylori biological properties revealed that the
      microorganism is involved in the first steps of gastric carcinogenesis as
      proposed by the Correa model (from normal gastric tissue through superficial
      gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to
      carcinoma). Significant correlation between the prevalence of H. pylori infection
      and incidence of gastric carcinoma (mainly the intestinal type) in various
      geographical areas has been reported. The high prevalence of HP in pre-neoplastic
      states and in cases of early gastric cancer indicates the infection would precede
      the development of gastric cancer. HP-related chronic inflammation of gastric
      mucosa with increased mucosal cell proliferation, deficit in local ascorbic acid
      concentration, topical ammonia toxicity are putative mechanisms that overexpose a
      weakened gastric mucosa to environmental carcinogens.

PMID- 7571981
TI  - Are perforated gastroduodenal ulcers related to Helicobacter pylori infection?
AB  - The prevalence of Helicobacter pylori gastritis in 36 patients with a perforated
      ulcer undergoing endoscopy prior to or at least 2 months after perforation was
      56%, intermediate between that of age and sex matched healthy blood donors (36%)
      who had measurement of circulating antibodies to Helicobacter pylori and of ulcer
      patients without perforation matched for age, sex and ulcer location (86%). In
      the 20 patients with Helicobacter pylori gastritis, 8 had a history of peptic
      ulcer and 7 of 9 patients with a follow-up of at least 12 months and no
      preventive treatment had a symptomatic relapse. The group of patients without
      infection included 6 young patients (< 40) who did not use non steroidal anti
      inflammatory drugs and 10 older patients (> 60): 9 used non steroidal anti
      inflammatory drugs and seven had a normal gastric mucosa on biopsy. One patient
      without Helicobacter pylori had a second perforation, the only relapse in this
      group. We conclude that patients with perforated ulcers are a heterogeneous group
      with a recurrent ulcer disease mainly in patients with Helicobacter pylori.

PMID- 7571982
TI  - Interrelationships between systemic hemodynamics, urinary sodium excretion, and
      renin-angiotensin system in cirrhosis.
AB  - We studied the interrelationships between systemic hemodynamics, sodium excretion
      and the renin-angiotensin system in 28 nonazotemic cirrhotic patients on a sodium
      restricted diet. Renal hemodynamics were also assessed. The patients were divided
      into three groups. Group A comprised 9 patients without ascites or edema; group B
      comprised 8 patients with ascites and relatively high sodium excretion (41.9 +/-
      12.9 mmol/day); and group C comprised 11 patients with ascites and very low
      sodium excretion (4.8 +/- 12.9 mmol/day). There were no significant differences
      in urine flow, glomerular filtration rate or effective renal plasma flow between
      the three groups of patients, although renin and aldosterone levels were
      significantly increased in group C. Groups A and B did not differ in hemodynamic
      parameters and no differences were found between the three groups in heart rate
      or in plasma volume. Group C, however, showed significantly higher cardiac index
      and lower arterial pressure and systemic vascular resistance. Plasma volume was
      inversely related to systemic vascular resistance, and natriuresis correlated
      significantly with both cardiac index (inversely) and systemic vascular
      resistance (directly). In addition, renin and aldosterone levels were inversely
      correlated with both mean arterial pressure and systemic vascular resistance. The
      systemic hemodynamic disturbances in nonazotemic cirrhotics is paralleled by the
      impairment in sodium homeostasis, suggesting that the decrease in systemic
      vascular resistance is the primary event leading to hypotension, high cardiac
      output and the activation of the renin-angiotensin system in these patients.

PMID- 7571983
TI  - [Can the L/A ratio identify acute alcoholic pancreatitis?].
AB  - Early distinction between acute alcoholic pancreatitis is important, because of
      possible emergency endoscopic sphincterotomy in case of biliary pancreatitis. The
      aim of this study was to evaluate the value of L/A ratio in the diagnosis of
      acute alcoholic pancreatitis. From 1990 to end 1993, 133 patients with acute
      pancreatitis were reviewed. Inclusion criteria were: 1) abdominal pain, 2)
      pathological serum amylase or serum lipase on admission or within 24 hours after
      beginning or abdominal pain, 3) acute pancreatitis at the echography or CT scan
      within 48 hours after admission. 60 patients met the inclusion criteria (31
      alcoholic pancreatitis, 19 biliary pancreatitis and 10 pancreatitis of other
      causes). L/A ratio was studied in terms of delay from beginning of abdominal
      pain. There was no statistical difference between alcoholic and biliary
      pancreatitis at any time of the study, with the exception of admission. AST, ALT
      and alkaline phosphatase were higher in biliary pancreatitis than in alcoholic
      pancreatitis. AST and ALT were the best biochemical tests to diagnose biliary
      pancreatitis. Blamey's criteria can also contribute to diagnose biliary
      pancreatitis. These biochemical tests are the most helpful if they are collected
      very soon in the evolution of acute pancreatitis. It is concluded that L/A ratio
      is not helpful in the diagnosis of alcoholic acute pancreatitis.

PMID- 7571985
TI  - Lymphocytic gastritis. Clinical and endoscopic presentation and long-term follow
      up.
AB  - Lymphocytic gastritis is a histopathological entity corresponding with diffuse
      varioliform gastritis but also with other gastroscopic findings. Eighteen
      patients were followed over a mean period of 25 months. The symptoms, the
      endoscopic and histopathological abnormalities remained unchanged in the majority
      of the cases. Conventional peptic ulcer therapy failed to control symptoms or to
      normalize endoscopic alterations. Helicobacter pylori did not seem to play a role
      in the pathophysiology. Lymphocytic duodenitis was found in four patients. The
      relationship between lymphocytic gastritis, Menetrier's disease and coeliac
      disease has further to be elucidated.

PMID- 7571984
TI  - Deficient antithrombin III activity and enhanced fibrinolysis in patients with
      liver disease: evidence against a cause-effect relationship.
AB  - To investigate the pathogenesis of fibrinolysis in liver disease, antithrombin
      III (AT III) activity, prothrombin fragment (F1 + 2) and d-dimer (D-DI) were
      measured in 50 patients with liver disease and in 17 healthy controls. Moreover,
      4 patients with cirrhosis were randomly assigned to receive either an intravenous
      infusion of AT III (at two different dosages) or placebo, with a crossover
      design. Increased levels of D-DI were detected in patients with cirrhosis and
      hepatocellular carcinoma in comparison both with control subjects and with
      patients with acute hepatitis or mild chronic liver disease. An inverse
      correlation was observed between AT III and D-DI (r = -0.755, P < 0.001, simple
      linear regression), while no correlation was found between D-DI or AT III and F1
      + 2. The correlation of the deficiency of AT III activity by infusion of human AT
      III did not result in any significant change (P0.10, analysis of variance for
      repeated measures) of the plasma concentration of either D-DI or F1 + 2, in
      comparison to placebo. Thus, advanced forms of chronic liver disease, but not
      acute hepatitis and mild forms of chronic liver disease, are associated with
      increased plasma concentrations of markers of fibrinolysis, which are inversely
      correlated with AT III activity. However, the correction of the deficient AT III
      activity does not affect the plasma concentration of either D-DI or F1 + 2,
      thence not supporting the hypothesis that enhanced fibrinolysis in advanced liver
      disease is the result of low-grade disseminated intravascular coagulation.

PMID- 7571986
TI  - Spontaneous exoneration of a colonic lipoma.
AB  - Colonic lipoma is a rare tumor. This tumor is usually asymptomatic. We report the
      case of a patient who complained of abdominal pain. Symptoms disappeared after
      spontaneous exoneration of a colonic lipoma.

PMID- 7571989
TI  - High-purity factor IX concentrates for treatment of hemophilia B: relative purity
      and thrombogenic potential.
AB  - Constituents other than factor IX have been implicated as etiologic agents for
      thrombotic complications in patients receiving prothrombin complex concentrates
      (PCCs). In vitro studies, in vivo animal models, and clinical evaluations in
      patients with hemophilia B indicate that high-purity factor IX concentrates
      contain significantly fewer potentially thrombogenic contaminants than PCCs. A
      recent in vitro study from our laboratory used highly sensitive assays to analyze
      the relative purity of these newer products. The following products were studied
      using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      analysis and immunoblotting: Aimafix, AlphaNine-SD, Factor IX VHP, Immunine,
      Mononine, Nanotiv, and 9MC (now known as Replinine). The mean specific activity
      of the high-purity factor IX products ranged from 68 IU factor IX/mg (Aimafix) to
      246 IU factor IX/mg (Mononine). SDS-PAGE analysis under reducing and nonreducing
      conditions showed that Mononine had the fewest contaminating bands. The
      immunoblot to detect factor IX showed a dominant factor IX band for all products,
      visible light chain of factor IX for all products except Aimafix, and another
      contaminating band visible at 49,500 daltons for all products except 9MC. High
      molecular weight contaminants were apparent for some products. Factor VIIa was
      detected in some lots of Immunine, Nanotiv and 9MC. Factor X and prothrombin
      contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv and 9MC.
      Thus, Mononine, Nanotiv and 9MC demonstrated the highest purity but no product
      was totally free of contaminants.

PMID- 7571988
TI  - The clinical [corrected] background of familial adenomatous polyposis. History,
      epidemiology, diagnosis and treatment.
AB  - Familial adenomatous polyposis (FAP) is a dominantly inherited genetic disorder
      predisposing to colon cancer through the early development of multiple
      adenomatous polyps in the large bowel. FAP is not restricted to the colon and
      rectum, but is a more complex disease which can potentially affect almost any
      organ not only with benign tumours but also with life threatening carcinomas.
      Desmoid tumours and gastroduodenal polyps and cancer are the two more worrying
      extracolonic manifestations of FAP. Recent advances in FAP knowledge, such as the
      report of congenital hypertrophy of the retinal pigment epithelium (CHRPE) or the
      APC gene identification, are very useful for screening and long-term follow-up of
      the patients through regional or national registries. Nutritional and
      pharmacological intervention trials are under way to assess potential new medical
      treatments of FAP. Surgery is still the only effective treatment for colorectal
      cancer prevention in FAP. The choice of a surgical procedure is controversial,
      but the introduction of total proctocolectomy with ileal pouch-anal anastomosis
      can be considered as a major advance in surgical treatment of FAP during the last
      decade.

PMID- 7571987
TI  - [Hepatic angiosarcoma developed 5 years following treatment for subacute
      glomerulonephritis].
AB  - A patient with hepatic angiosarcoma is described. This tumour, thought rare,
      still generates clinical interest, because of its characteristic association with
      occupational exposure to certain chemicals such as vinyl chloride and thorotrast.
      That association has led to extensive screening of high risk populations. An
      additional case of liver angiosarcoma which probably developed following long
      term treatment with cyclophosphamide. The significant aspects of this tumour are
      delineated and the diagnostic modalities are discussed.

PMID- 7571990
TI  - In vivo models of thrombogenic potential: usefulness and limitations.
AB  - The thrombogenicity of prothrombin complex concentrates (PCCs) has been known as
      a risk factor since their first clinical use about 30 years ago. The development
      of in vivo models to define the thrombogenic components in PCCs was instrumental
      in providing a logical basis for selecting in vitro assays to screen for the
      distribution of such components during the manufacture of PCCs, and to minimize
      their appearance in the final product. Even so, these thrombogenic components are
      not completely removed, as shown in our canine nonstasis model of
      thrombogenicity: PCCs were still found to elicit a thrombogenic response, shown
      by increased fibrinopeptide A, fibrin(ogen) degradation products, activated
      partial thromboplastin time, and decreased fibrinogen and platelet counts when
      clinically relevant doses were used. The new generation of high-purity factor IX
      (HP-FIX) concentrates differs from PCCs because these products contain only
      negligible amounts of clotting factors other than factor IX, lower amounts of
      activated clotting factors, and, in products we have assayed, no coagulant-active
      phospholipids. When we infused a number of HP-FIX products in the canine
      nonstasis model, no thrombogenic response was observed at doses considerably
      greater than PCC doses that did elicit a response. Likewise, HP-FIX products were
      much less thrombogenic than PCCs when tested in small-animal stasis and nonstasis
      thrombogenicity models. Small-animal models are also useful for evaluating the
      role of factor IXa as a potential thrombogenic contaminant of concentrates and
      ensuring minimal amounts in the final product. The limitations associated with
      extrapolating in vivo model data will be shown to be minimal if ongoing clinical
      studies continue to demonstrate the low thrombogenic potential of HP-FIX
      concentrates in humans.

PMID- 7571991
TI  - The need for highly purified products to treat hemophilia B.
AB  - Thromboembolic complications of prothrombin complex concentrate (PCC) therapy
      were first reported by Kasper in 1973 [N Engl J Med 1973;289:160]. The following
      contaminants were discussed as possible contributors to the thrombogenicity risk:
      the presence of other zymogens in PCCs, the presence of activated factor IX or
      activated factor X, or the presence of phospholipids from platelets resulting
      from insufficient centrifugation of the donor plasma. Activated factor IX is now
      accepted as a major causative factor. After numerous additional reports of
      thromboembolic complications in patients treated with PCCs, the International
      Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization
      Committee (SSC) Thrombogenicity Registry was established in 1988. Lusher
      collected 72 cases worldwide for the SSC/ISTH in 1988 and 1989. Thromboembolic
      complications and myocardial infarctions, however, continue to be serious
      problems associated with PCC therapy--even in the 1990s--underscoring the urgent
      need for high-purity factor IX products. Results from several studies by
      Mannucci, Bauer, and other authors demonstrated that patients treated with high
      purity products developed no activation of prothrombin or thrombin, as indicated
      by appearance of thrombogenicity markers such as fibrinopeptide A and the amino
      terminal fragments of prothrombin (F1 + 2). Other authors demonstrated that in
      patients at high risk for thrombotic complications, particularly those with liver
      disease, or postsurgery, or in those requiring repeated treatments, high-purity
      concentrates appear to be safe, regarding both thrombosis and risk of virus
      transmission.

PMID- 7571992
TI  - Improved safety from plasma derivatives: purification and viral elimination
      characteristics of mononine.
AB  - The occurrence of viral transmission with coagulation factor concentrates treated
      with a single virus elimination step has resulted in a consensus that multiple
      virus elimination steps must be incorporated in the processing of these proteins.
      As an example of this methodology, the steps included in the purification of the
      factor VIII concentrate Monoclate-P are reviewed and those used to purify the
      factor IX concentrate Mononine--monoclonal antibody chromatography, sodium
      thiocyanate incubation, and a novel ultrafiltration system--are described.
      Rigorous quality control/quality assurance during processing is essential. The
      ultimate safety of the product used clinically further requires monitoring of
      long-term stability and verification of the absence of neoantigens that could
      stimulate unusual levels of antibody formation. Standardization of regulatory
      compliance will further strengthen the safety of all products. The zeal to add
      further barriers to viral contamination should not compromise the timely
      assessment of these additional protections.

PMID- 7571993
TI  - Continuous infusion of factor concentrates: review of use in hemophilia A and
      demonstration of safety and efficacy in hemophilia B.
AB  - Continuous infusions of factor VIII have proved feasible in patients with
      hemophilia A, and the hemostatic efficacy has sometimes been superior to that of
      repeated bolus injections of factor VIII. Avoiding dangerously low trough levels
      by maintaining a constant therapeutic level not only promotes hemostasis but
      requires substantially less factor concentrate, which represents a considerable
      saving. Only limited data on continuous infusion of factor IX are available, but
      these data suggest similar benefits. An investigation of the stability of four
      prothrombin complex concentrates and three highly purified factor IX concentrates
      is described, as is the successful treatment of four hemophilia B patients with
      continuous infusions of Mononine.

PMID- 7571994
TI  - Concomitant treatment with factor IX concentrates and antifibrinolytics in
      hemophilia B.
AB  - Concomitant use of the monoclonal antibody-purified factor IX concentrate
      (Mononine, Armour Pharmaceutical Company, Collegeville, Pa.) and two
      antifibrinolytic agents, epsilon-aminocaproic acid (EACA; Amicar, Immunex,
      Seattle, Wash.) or tranexamic acid (AMCA; Cyklokapron, Kabi Pharmacia,
      Piscataway, N.J.) was examined for safety and efficacy in patients with
      hemophilia B. In a retrospective review of 19 patients treated with monoclonal
      antibody-purified factor IX and EACA on 35 occasions, bleeding was successfully
      controlled and no instances of clinical thrombotic complications were reported;
      one instance of urticaria resolved without additional treatment. The use of EACA
      or AMCA in combination with monoclonal antibody-purified factor IX was also
      examined prospectively in a study of 9 patients. Bleeding was effectively
      controlled and no thrombotic events were detected clinically with either
      antifibrinolytic agent. No significant changes in hematocrit or hemoglobin were
      detected, and there was no evidence of thrombosis as evaluated clinically and by
      sensitive molecular markers. It was concluded from both the retrospective and
      prospective data that monoclonal antibody-purified factor IX concentrate in
      combination with an antifibrinolytic agent does not activate the coagulation
      cascade and is a safe and effective treatment for prevention and control of oral
      bleeding in hemophilia B patients.

PMID- 7571995
TI  - Gene mutations and inhibitor formation in patients with hemophilia B.
AB  - The nature of the mutation in the factor IX gene is an important factor in
      determining whether a patient with hemophilia B will develop an inhibitor. In a
      series of 62 Swedish families with hemophilia B, including 30 with the severe
      form, approximately one third of the families exhibiting deletions or nonsense
      mutations contained one member who developed an inhibitor. The risk for inhibitor
      development in family members carrying missense mutations was virtually zero.

PMID- 7571996
TI  - Safety and recovery of mononine in multiple-dose, high-dose regimens.
AB  - Prothrombin complex concentrates (PCCs) have been used for the treatment of
      hemorrhagic episodes in patients with hemophilia B but have been associated with
      a high incidence of thrombotic complications. Newer, ultrapure concentrates of
      factor IX contain less extraneous proteins than PCCs and are less thrombogenic in
      vitro. In this report, the results of clinical studies with Mononine (Armour
      Pharmaceutical Company), a purified factor IX concentrate prepared by monoclonal
      affinity chromatography, are described. Two studies were performed, a phase I/II
      clinical trial in 10 patients and a compassionate use study in 72 patients. The
      pharmacokinetics of Mononine were found to be similar to the pharmacokinetics of
      factor IX after administration of PCCs. In both studies, Mononine was well
      tolerated and hemostatically effective when used in doses of up to 161 IU/kg in
      treatment courses of up to 67 infusions of Mononine. Patients with hepatitis and
      a prior history of thrombosis with PCCs tolerated Mononine with no evidence of
      thrombosis. The only thrombotic complication attributed to Mononine in the two
      studies was an episode of phlebitis at the site of an intravenous line in one
      patient. These studies indicate that Mononine is safe and effective in the
      treatment of hemorrhagic episodes in patients with hemophilia B.

PMID- 7571998
TI  - The golden years? Myths and realities.

PMID- 7571997
TI  - Properties of factor IX concentrates.
AB  - Five purified concentrates--Nanotiv (Kabi Pharmacia), Immunine (Immuno), Factor
      IX VHP (Biotransfusion), Alphanine (Alpha Therapeutic Corporation), and Mononine
      (Armour Pharmaceutical Company)--were characterized biochemically and their in
      vivo pharmacokinetic and thrombogenic properties evaluated. The results were
      compared with those for two prothrombin complex concentrates (PCCs): Preconativ
      (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for factor
      IX coagulant activity (FIX:C) generally agreed with the manufacturers' labeled
      values. The purified concentrates were virtually devoid of other vitamin K
      dependent coagulation factors, the inhibitor proteins C and S, and either
      fibrinogen, fibronectin, or immunoglobulins. Indicators of thrombin generation
      (i.e., prothrombin fragments F1 + 2 and thrombin-antithrombin complex) were
      present in varying amounts in all preparations. The level of specific activity in
      the purified concentrates exceeded that in the PCCs by a factor of 50- to 100
      fold. Pharmacokinetic variables were studied in severe hemophilia B patients:
      Nanotiv was compared with Preconativ; Immunine was compared with Prothromplex
      TIM4 in crossover studies; and Mononine was tested in a single-drug study. No
      differences were apparent between Nanotiv, Preconativ, and Mononine, but recovery
      rates were lower, clearance rates higher, and FIX:C half-life shorter for
      Immunine and Prothromplex TIM4, although the disparate results might have been
      attributable to methodologic differences. Purified factor IX concentrates were
      used successfully as cover for surgery and in immune tolerance induction without
      observable adverse effects.

PMID- 7571999
TI  - A concept analysis of caring.

PMID- 7572000
TI  - Clinical comment on the Dermapulse Wound Management System [corrected].

PMID- 7572003
TI  - The European Diploma in Anaesthesiology and Intensive Care of the European
      Academy of Anaesthesiology.

PMID- 7572002
TI  - The accuracy of reference lists in Acta Anaesthesiologica Scandinavica.
AB  - To determine the accuracy of bibliographic citation in Acta Anaesthesiologica
      Scandinavica, we reviewed all 1990 volumes and part of 1994 volumes of the
      journal and sequentially numbered all references appearing in those years (n =
      2701 and 2158 in 1990 (No. 1-No. 8) and 1994 (No. 1-No.5), respectively). We
      randomly selected 100 references from each year. After citations of nonjournal
      articles were excluded, the remaining 195 citations were carefully scrutinized.
      Authors' names, article title, journal title, volume number, page numbers, and
      year were examined in each selected reference. A reference was deemed correct if
      each element of the citation was identical to its source. Of the examined
      references, 40% and 45% contained one or more errors in 1990 and 1994,
      respectively. The elements most likely to be inaccurate were, in descending order
      of frequency, article title, author, and page number. No significant differences
      existed in the error rate between the two years. We have found many citation
      errors in the reference lists of Acta Anaesthesiologica Scandinavica and no
      improvement in these latest four years. All contributors to Acta
      Anaesthesiologica Scandinavica should thoroughly check the accuracy of reference
      lists.

PMID- 7572001
TI  - The role of medications in treating the behavioural disturbances of dementia
      sufferers.

PMID- 7572004
TI  - The effect of ketanserin upon postoperative blood pressure, cerebral blood flow
      and oxygen metabolism in patients subjected to craniotomy for cerebral tumours.
AB  - Hypertension and cerebral hyperperfusion are often seen in the immediate
      postoperative period after craniotomy for supratentorial tumours. This study was
      performed to evaluate the effect of ketanserin, given at the end of the
      peroperative period, upon cerebral blood flow (CBF), and cerebral metabolic rate
      of oxygen (CMRO2) before extubation. Mean arterial blood pressure (MABP),
      cerebral arterio-venous oxygen content difference (AVDO2), PaO2, and PaCO2 were
      repeatedly measured during the operation, and 180 minutes after extubation. Ten
      patients were included in this study. The results were compared to those from a
      recent study in which ten patients served as control. All patients were
      anaesthetized with thiopentone, fentanyl, nitrous oxide 67%, halothane 0.5%
      anesthesia. Ten patients were given ketanserin 10-20 mg (mean 18.5 mg) before
      extubation. There was no significant difference in CBF- and CMRO2 values between
      the two groups. During the period between closure of the dura and 5 minutes after
      extubation, an increase in MABP was observed in the control group (P < 0.05) but
      not in the ketanserin group. During the same period, a decrease in AVDO2 was
      observed in both groups (P < 0.05) and during the next 10 minutes an increase was
      observed. However, no difference in AVDO2 values between the two groups was
      found. These findings suggest that peroperative treatment with ketanserin reduces
      postoperative hypertension without influencing the cerebral blood flow or
      metabolism.

PMID- 7572005
TI  - Low flow anaesthesia reduces occupational exposure to inhalation anaesthetics.
      Environmental and biological measurements in operating room personnel.
AB  - In the present study we evaluated the occupational exposure to N2O and isoflurane
      during open circuit (OC) (fresh gas flow > or = minute volume) and low flow (LF)
      (fresh gas flow = 1.5 l/min) anaesthesia. The effects of active scavenging and of
      a charcoal filter positioned on the exhausting branch of the ventilator on
      environmental and urinary concentrations of inhalation anaesthetics were also
      investigated. The study was carried out in the same operating room provided with
      non-recirculating air changes (10 per hour). It involved anaesthetists and nurses
      during routine activity. N2O and isoflurane concentrations (time-weighted
      average) were measured after 3-hour continuous exposure: 1) in the environment at
      the level of the personnel's breathing zone (Ci); 2) in the environment at the
      ventilator zone (C); 3) in urine (Cu). During OC anaesthesia without active
      scavenging the breathing zone concentration of both N2O and isoflurane was very
      high (194.6 +/- 15.2 and 5.0 +/- 0.4 ppm, respectively). The activation of the
      scavenging greatly reduced the breathing zone concentration of N2O (31.6 +/- 4.1
      ppm) and isoflurane (1.7 +/- 0.2 ppm). LF anaesthesia (with active scavenging)
      significantly reduced the environmental concentration of both anaesthetics (Ci
      N2O and isoflurane 22.7 +/- 1.8 and 0.6 +/- 0.04 ppm, respectively). During LF
      anaesthesia the breathing zone concentration of N2O remained low, even without
      scavenging (22.7 +/- 1.8 ppm). Similar results were obtained by measuring N2O and
      isoflurane concentrations at the ventilator zone and in urine.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7572006
TI  - Desmopressin acetate does not reduce blood loss during total hip replacement in
      patients receiving dextran.
AB  - The blood loss-reducing effect of desmopressin during dextran therapy was studied
      in a double-blind fashion in 79 elderly but otherwise healthy patients with
      preoperative normal bleeding time undergoing total hip replacement for primary
      coxarthrosis. An infusion of desmopressin (0.3 microgram/kg body weight) or
      placebo was randomly administered immediately after administration of spinal
      anaesthesia and six hours later. Haemostasis was evaluated on the basis of vWF:
      ristocetin cofactor activity, FVIII: C activity, human tissue plasminogen
      activator (tPA) plasminogen activator inhibitor type (PAI), beta-thromboglobuline
      (beta TG) and a clot impedance test (Sonoclot). There were no statistically
      significant differences (P > 0.05) in mean blood loss or transfusion requirements
      between the placebo and the desmopressin group. There was a significantly
      increase (P < 0.01) both in vWF: ristocetin cofactor and in FVIII: C activity
      after both infusions of desmopressin compared with placebo. There was no
      significant difference in beta TG, tPA, PAI or Sonoclot analysis between the
      groups. In conclusion, desmopressin did not reduce blood loss in patients
      undergoing total hip replacement.

PMID- 7572007
TI  - Effect of dopexamine on calculated low gastric intramucosal pH following valve
      replacement.
AB  - Gastric tonometry was used to study the possible effect of dopexamine infusion on
      a low calculated intramucosal pH (pHi) as a sign of splanchnic ischemia.
      Measurements were made during surgery and for approximately 18 hours
      postoperatively on 19 non-selected adult patients undergoing valve replacement.
      Patients developing a postoperative pHi > 7.30 were randomized to receive
      dopexamine (2 micrograms.kg-1 min-1) or placebo in a double blind fashion.
      Eighteen patients were randomized, 10 to receive dopexamine and 8 to placebo. The
      calculated pHi remained unchanged for the first 2 hours in both groups. After 4
      hours a significant (P < 0.05) decrease in pHi was noted in the dopexamine group
      which remained significantly below the placebo group during the monitoring
      period. The dopexamine treated patients had a significantly longer period of low
      pHi but the pH-gap i.e. the difference between arterial pH and pHi did not differ
      between the two groups. Patients with postoperative complications, defined as
      infections (2), myocardial infarction (1), single- (2) or multiple organ failure
      and death (1), did not have longer periods with pHi below 7.30. In these
      patients, however, a pH-gap > 0.12 occurred more often than in those without
      complications, indicating that an increased incidence of complications was
      related to a pH-gap > 0.12. It is our opinion that true mucosal ischemia is best
      detected by estimating the difference in carbon dioxide tension between arterial
      blood and mucosa. This can be expressed either directly as PCO2-gap (PtonCO2
      PaCO2) or indirectly as pH-gap.

PMID- 7572008
TI  - Postdural puncture headache (PDPH): onset, duration, severity, and associated
      symptoms. An analysis of 75 consecutive patients with PDPH.
AB  - Among 873 consecutive patients who had undergone a total of 1021 spinal
      anaesthesias involving puncture of the lumbar dura, 75 (7.35%) complained of
      Postdural Puncture Headache (PDPH). The severity of each patient's PDPH was
      categorized, on a scale from mild to severe, on the basis of the onset, duration,
      severity of the headaches, and the degree to which they were accompanied by
      auditory and vestibular symptoms. In the patients who developed PDPH, 65%
      developed symptoms within 24 hours of the lumbar punctures and 92% developed
      symptoms within 48 hours. For the patients who recovered spontaneously the mean
      duration of the PDPHs was 5 days, with a range of 1-12 dyas. PDPH was
      characterized by headaches that were influenced by the patient's posture and the
      severity of PDPH was categorized as follows: Mild PDPH resulted in a slight
      restriction of their physical activity. These patients were not confined to bed
      and had no associated symptoms. Moderate PDPH forced the patient to stay in bed
      for part of the day, and resulted in restricted physical activity. Associated
      symptoms were not necessarily present. Severe PDPH. Patients were bedridden for
      the entire day and made no attempt to raise their head or to stand. Associated
      symptoms were always present. Forty-five of the PDPH patients (60%) recovered
      spontaneously. Of these, 8 patients (11%) were categorized as mild cases of PDPH,
      14 (19%) as moderate, and 23 (30%) patients as severe cases of PDPH. Thirty of
      the PDPH patients (40%) were treated with an autologous epidural blood patch
      (AEBP). Of these, 27 patients (36%) were classified as severe and 3 patients (4%)
      as moderate PDPH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572009
TI  - Epidural blood patch illustrated by CT-epidurography.
AB  - Four patients, who received epidural blood patch to treat postdural puncture
      headache, were examined with computed tomography in order to demonstrate the
      distribution of the injected blood. Blood alone could not be identified, but
      adding 2 ml contrast agent Iohexol 180 mg J/ml (Omnipaque, Nycomed Imaging) to 18
      ml blood gave an excellent demonstration of the distribution of the blood in the
      epidural space, both cranio-caudally (7-14 segments) and spatially in relation to
      the epidural septae. The blood-contrast media had a strong affinity to the dural
      sac. There was no support of the space filling effect of blood patch.

PMID- 7572010
TI  - Effects of organic nitrate vasodilators on platelet function before and after
      cardiopulmonary bypass.
AB  - Various in vitro, ex vivo and in vivo tests have shown that organic nitrates
      attenuate platelet function. Because organic nitrates are commonly administered
      to patients undergoing cardiac surgery, the postoperative bleeding tendency
      observed in these patients might be strengthened by nitrates. Therefore, we
      compared the acute effects of nitroglycerin (0.5 micrograms kg-1 min-1) and
      isosorbide dinitrate (0.5 or 2.5 micrograms kg-1 min-1) with those of placebo on
      platelet function both before and after cardiopulmonary bypass in 40 patients
      undergoing coronary artery bypass grafting (CABG). Bleeding time, platelet
      retention on glass beads, i.e. platelet adhesiveness, and thromboelastograph
      tracings were used as indicators of platelet function. Although nitroglycerin and
      isosorbide dinitrate induced significant haemodynamic changes, e.g. decreases in
      arterial and pulmonary arterial pressure, they had no significant effects on the
      indices of platelet function. We conclude that, when given in haemodynamically
      effective doses, neither nitroglycerin nor isosorbide dinitrate have any
      measurable acute effect on platelet function as evaluated with on-site tests in
      patients undergoing CABG surgery.

PMID- 7572011
TI  - The effects of midazolam, droperidol, fentanyl, and alfentanil on phagocytosis
      and killing of bacteria by polymorphonuclear leukocytes in vitro.
AB  - Polymorphonuclear leukocytes (PMNL) make an outstanding contribution to the
      defence against invading bacteria. We studied the effects of midazolam,
      droperidol, fentanyl, and alfentanil on phagocytosis and killing of
      Staphylococcus aureus and Escherichia coli by PMNL in vitro. Using a method
      described by Eggleton et al., PMNL were isolated from venous blood samples
      obtained from ten volunteers. The fluorescence microscopic method mentioned by
      Bellinati-Pires et al. was used to examine phagocytosis and killing. Whereas both
      midazolam and droperidol caused a significant inhibition of phagocytosis as well
      as bactericidal activity, fentanyl and alfentanil did not influence these PMNL
      functions. In order to find out whether midazolam and droperidol are able to
      intensify perioperative bacterial infections in vivo as well, additional clinical
      studies should be conducted.

PMID- 7572012
TI  - The metabolic effects of oral tizanidine in healthy volunteers.
AB  - This pilot study compared the metabolic effects of placebo and 6 mg and 12 mg of
      oral tizanidine in random double-blind cross-over fashion in five healthy
      volunteers. The metabolic measurements were made with a portable metabolic chart
      (Deltatrac, Datex/Instrumentarium, Helsinki, Finland). Heart rate (HR), systolic
      (BPS), mean (BPM) and diastolic (BPD) blood pressure were measured noninvasively.
      Subjective assessment of tiredness and dryness of mouth were measured by using
      visual analogue scales (VAS). There were no statistically significant differences
      in tiredness or dryness of mouth between the groups. BPD decreased significantly
      after both doses of tizanidine when compared to placebo (by an average of 12%
      after 6 mg of tizanidine and 15% after 12 mg of tizanidine from the baseline).
      Oxygen consumption and energy expenditure decreased significantly after 6 and 12
      mg of tizanidine when compared to placebo. The average decrease in oxygen
      consumption was 3% after 6 mg of tizanidine and 8% after 12 mg of tizanidine,
      when compared to the baseline. Energy expenditure decreased by an average of 5%
      after 6 mg of tizanidine and 9% after 12 mg of tizanidine, when compared to the
      baseline. There were no other statistically significant differences between the
      groups. This study indicates that 6 and 12 mg of oral tizanidine can be useful
      for reducing energy expenditure and oxygen consumption without prominent
      cardiovascular effects.

PMID- 7572013
TI  - Premedication with sublingual buprenorphine for out-patient arthroscopy: reduced
      need for postoperative pethidine but higher incidence of nausea.
AB  - The effect of preoperative sublingual buprenorphine (B) on postoperative pain
      (VAS), the need for postoperative opioid injections and on time to discharge, was
      evaluated in a prospective randomised double-blind study. Forty ASA I-II patients
      scheduled for arthroscopy of the knee received premedication with 0.4 mg
      buprenorphine (group B) and 42 patients were given placebo (group P).
      Postoperatively, pethidine was given to patients with pain. Three of the 40
      patients in group B vs 11 of the 42 in group P received pethidine (P < 0.05). In
      group B, however, 13 of the 40 patients complained of nausea, prolonging median
      time to discharge from 155 to 255 minutes (P < 0.05). In group P, 3 of the 42
      patients were nauseated, P < 0.01, compared with group B. Time to discharge did
      not differ between the groups in patients without nausea. The median respiratory
      rate was significantly lower in group B, but no patient required ventilatory
      support. In conclusion, premedication with sublingual buprenorphine cannot be
      recommended for this procedure. It reduces the need for postoperative injections
      of pethidine but increases the incidence of postoperative nausea which prolongs
      the recovery time. Careful monitoring is also mandatory because of the
      possibility of respiratory depression.

PMID- 7572014
TI  - Reliability of CO2 measurements from the airway by a pharyngeal catheter in
      unintubated, spontaneously breathing subjects.
AB  - Although several short communications have appeared describing attempts to record
      the concentrations of carbon dioxide (cCO2) from the unintubated airway by a
      catheter placed in the nose, so far only few reports have documented the
      reliability of the method. To evaluate the reliability of CO2 measurements by a
      catheter in the open, unintubated airway during spontaneous respiration, a 12 CH
      PVC catheter was forwarded through the nostril to the hypopharynx and connected
      to a capnograph in nine healthy volunteers. Another capnograph was connected to a
      tightly fitting face mask and simultaneous CO2 recordings were attained from the
      two parts of the airway during normoventilation, hyperventilation and
      rebreathing. A corresponding blood sample was drawn from the radial artery for
      blood gas analysis. The configurations of the capnograms recorded from the
      pharyngeal catheter were similar to those recorded from the face mask. The
      results were analysed by a multifactor analysis of variance. The carbon dioxide
      tension (pCO2) was significantly influenced by degree of ventilation (P <
      0.0001), subject (P < 0.0001), measurement site (P = 0.030) and interaction
      subject-ventilation (P = 0.015). In spite of the significant influence of the
      measurement site, the difference between end tidal carbon dioxide tension
      (pCO2(ET)) and carbon dioxide tension in arterial blood (pCO2(a)) was small. The
      mean differences between paired measurements (pCO2(ET)-pCO2(a)) were -0.10 kPa +/
      0.41 kPa (mean +/- SD) for the catheter and -0.20 kPa +/- 0.43 kPa for the face
      mask. The study demonstrates that reliable recordings of CO2 concentrations
      during spontaneous respiration can be obtained by a thin catheter positioned in
      the hypopharynx.

PMID- 7572015
TI  - Peroperative and immediate postoperative adverse events in patients undergoing
      elective general and orthopaedic surgery. The Gothenburg study of perioperative
      risk (PROPER). Part II.
AB  - All anaesthetic and surgical procedures impose a certain risk of complications.
      However, reliable estimates of this risk from prospective studies are rare. This
      study is a prospective clinical epidemiological study of 1361 consecutive
      patients subjected to elective general and orthopaedic surgery. These patients
      were followed from an extensive preoperative assessment to three months after the
      operation. In this report the peroperative and early postoperative period in the
      postoperative care unit or intensive care unit is described. General anaesthesia
      was given to 59% and regional/local anaesthesia to 41%. Adverse peroperative
      events occurred in 19%. The most common were circulatory events (11%),
      respiratory (4%), and allergic events (1%). Most events were of minor severity.
      However, with the official registration system, only 1 out of 8 events was
      detected. In the postoperative unit one or more adverse event was noted in 47% of
      the cases. These were dominated by circulatory (18.4%) and respiratory events
      (5.0%). CNS depression was noted in 6.8% of the cases. Most per- and
      postoperative event variables were highly correlated to the degree of surgical
      stress. In conclusion, a new concept for preoperative assessment and the
      registration of events during and after surgery was used. In this way, a large
      number of events of importance, not least for quality assurance, were found that
      would be missed with the official coding system. In a previous report we could
      show that even minor events affected the cost of care substantially.

PMID- 7572016
TI  - Nitrous oxide is a potent cerebrovasodilator in humans when added to isoflurane.
      A transcranial Doppler study.
AB  - Nitrous oxide during neurosurgical procedures is almost always given in
      combination with either volatile or intravenous anesthetics. The modifying
      influence of such interventions has been studied clinically and in experimental
      settings; the reported findings, however, are inconsistent. The present study
      compares the cerebrovascular effects of MAC equivalent concentrations of
      isoflurane alone and isoflurane plus nitrous oxide. Twenty lumbar laminectomy
      patients randomized either to receive isoflurane or isoflurane plus nitrous oxide
      were investigated over a dose range from 0.5 to 1.5 MAC. A transcranial Doppler
      (TCD) ultrasonography device was used to measure cerebral blood flow velocity
      (CBFV) in the right middle cerebral artery (MCA) as an index of anesthetic
      induced alterations in cerebral blood flow (CBF). A small but marginally
      significant decrease in CBFV at 1 MAC and no change at 1.5 MAC occurred in the
      isoflurane anesthetized patients. In contrast, a small but significant increase
      in CBFV at 1 MAC and a very significant increase at 1.5 MAC occurred in the
      isoflurane plus nitrous oxide anesthetized patients. Nitrous oxide added to an
      isoflurane anesthetic regimen is concluded to be a potent vasodilator. In
      addition, the vasodilating effects of nitrous oxide were not uniform; they
      progressively increased with an increasing isoflurane concentration.

PMID- 7572017
TI  - Diltiazem does not increase ventricular fibrillation threshold during
      hypothermia.
AB  - This study was designed to investigate whether the calcium channel blocker
      diltiazem affects the threshold for ventricular fibrillation during hypothermia
      in dogs. Ten dogs were cooled from 37 to 25 degrees C and rewarmed to 37 degrees
      C. The threshold for ventricular fibrillation was determined at body temperatures
      37, 34, 31, 28 and 25 degrees C by programmed electrical stimulation using a
      stimulation protocol which involved application of maximal five extrastimuli. At
      25 degrees C, six dogs were given an i.v. bolus dose of 100 micrograms.kg-1
      followed by a continuous infusion of 100 micrograms.kg-1.h-1 of diltiazem
      hydrochloride. The other four dogs, were given no drugs at 25 degrees C and
      served as a control group. The dogs were rewarmed, and the stimulus protocol was
      performed at the same temperatures as during cooling. Cooling from 37 to 25
      degrees C reduced the threshold for ventricular fibrillation in both groups.
      Heart rate were reduced, monophasic action potential duration at the apex and
      base of the heart increased from 167 +/- 5 ms to 469 +/- 17 ms and from 164 +/- 5
      ms to 466 +/- 17 ms, respectively, when the temperature was reduced. The
      ventricular effective refractory period increased from 176 +/- 9 ms at 37 degrees
      C to 472 +/- 15 ms at 25 degrees C. Cooling increased QRS time on the ECG from 55
      +/- 4 ms to 138 +/- 13 ms. Addition of diltiazem at 25 degrees C did not affect
      the threshold for ventricular fibrillation during rewarming. Further, diltiazem
      at 25 degrees C did not affect the heart rate or refractoriness.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572018
TI  - Gastric tonometry: effect of sucralfate on calculated intramural pH.
AB  - Tonometric measurement of gastric intramural pH (pHi) is a noninvasive method to
      assess adequacy of splanchnic perfusion. Calculation of pHi may be influenced by
      various factors. This prospective study was designed to determine if stress ulcer
      prophylaxis with sucralfate interferes with pHi measurement. Twenty-five adult
      patients admitted to the intensive care unit (ICU) after open heart surgery were
      studied. Nasogastric tonometers were placed. Patients received sucralfate 1 g via
      the nasogastric tube 8 hours after termination of surgery, thereafter every 6
      hrs. Gastric luminal pH and intramural pH were determined immediately prior and 1
      hour after the first sucralfate administration. Gastric intramural pH was
      calculated from the arterial HCO3- concentration and the tonometrically
      determined intraluminal PCO2 value using the Henderson-Hasselbalch equation.
      Intraluminal PCO2(ss) was measured to 6.86 +/- 0.75 kPa prior to sucralfate
      administration as compared to 6.96 +/- 0.68 kPa 1 hour after 1 g sucralfate (P =
      0.92). Intramural pH, as calculated by tonometry, was 7.31 +/- 0.05 vs 7.31 +/-
      0.05, and was thus not influenced by sucralfate administration (P = 0.97). Mean
      gastric intraluminal juice pH was 4.2 +/- 1.3 compared to 4.2 +/- 1.2 (P = 0.59).
      These data suggest that sucralfate does not interfere with tonometrically
      determined intraluminal PCO2 measurement and calculation of gastric intramural
      pH.

PMID- 7572020
TI  - Are the cardiovascular actions of dopamine altered by isoflurane?
AB  - Dopamine seems theoretically to be a rationale choice when adrenergic support is
      needed to counter undesired cardiovascular depressant effects of isoflurane.
      Although the cardiovascular effects of isoflurane (ISO) and exogenous dopamine
      (DA) are well documented, there are no reports on their pharmacological
      interaction. The effects of ISO 1.4% (MAC 1.0) on the cardiovascular response to
      exogenous DA were studied in dogs during chloralose anesthesia. Instrumentation
      included catheterizations of the femoral artery (for aortic pressures and heart
      rate, HR), the pulmonary artery (for thermodilution cardiac output, CO, and
      pulmonary arterial pressures) and the left ventricle (for tip-manometer measured
      left ventricular end-diastolic pressure, LVEDP). ISO per se decreased HR (-16%),
      mean arterial pressure (MAP; -33%), CO (-29%), left ventricular dP/dt (LV dP/dt; 
      51%), and increased pulmonary artery occlusion (PAOP; +64%) and LVEDP (+28%).
      Prior to ISO, DA increased MAP, CO stroke volume (SV), LV dP/dt and LV dP/dt/SAP
      (systolic arterial pressure) at the dose 10 micrograms.kg-1.min-1. At the dose 20
      micrograms.kg-1.min-1 DA, besides these effects, increased PAOP and mean
      pulmonary artery pressure (MPAP). During ISO, DA at the dose 10 micrograms.kg
      1.min-1 restored MAP, CO, and SV to pre-ISO control levels, while LV dP/dt was
      increased to +96% above the pre-ISO control level. At the dose 20 micrograms.kg
      1.min-1, DA increased MAP (+33%), LV dP/dt (+172%), PAOP (+132%) and MPAP (+50%)
      above pre-ISO control levels. The cardiac effects of DA were similar to when it
      was given alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572019
TI  - Fluid balance and pulmonary functions during and after coronary artery bypass
      surgery: Ringer's acetate compared with dextran, polygeline, or albumin.
AB  - The effects on fluid balance, pulmonary functions and economics were evaluated in
      a randomized comparison of one colloid free and three colloid containing fluid
      regimens, for 48 hours during and after coronary artery bypass (CAB) surgery. A
      standard regimen for anaesthesia, extracorporeal circulation and monitoring was
      used. Only Ringer's acetate (RAc) was used as priming solution for extracorporeal
      circulation. Forty patients were randomized to receive either RAc, polygeline 35
      mg.ml-1 (Haemaccel), dextran 70 (Macrodex) 60 mg.ml-1, or albumin 40 mg.ml-1 in
      saline whenever fluid volume was needed to stabilize haemodynamics. At the end of
      the operation, fluid retention was significantly lower in patients receiving
      polygeline and dextran 70, compared with patients receiving RAc. At 48 hours,
      however, there were no differences in cumulative fluid balance. Patients in the
      colloid groups postoperatively had a higher serum colloid osmotic pressure (s
      COP), but a higher net lung capillary filtration pressure (delta P) only on the
      second postoperative day than the RAc group. However, this did not adversely
      affect intrapulmonary venous admixture, arterial oxygen tension, or time on
      respirator in the RAc group compared with the colloid groups. The most expensive
      colloid fluid regimen (albumin) cost about 230 US$ more per patient than the RAc
      fluid regimen. We conclude that Ringer's acetate for volume replacement to
      stabilize haemodynamics during and after CAB surgery is associated with increased
      fluid retention only during the intraoperative period, compared with dextran 70
      or polygeline, and with a lower serum colloid osmotic pressure and net lung
      capillary filtration pressure postoperatively, compared with all three colloid
      groups. This does not affect pulmonary functions adversely.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7572021
TI  - Methylmethacrylate monomer produces direct relaxation of vascular smooth muscle
      in vitro.
AB  - Methylmethacrylate bone cement is associated with severe hypotensive reactions
      during surgery and anesthesia. The purpose of this in vitro study was to
      determine if methylmethacrylate monomer could produce hypotension by acting
      directly on vascular smooth muscle. Segments of human saphenous vein or rabbit
      thoracic aorta were cut into rings. The rings were mounted in isolated tissue
      chambers in order to measure isometric tension development. Methylmethacrylate
      monomer (methylmethacrylic acid ester) produced direct relaxation of venous or
      aortic rings preconstricted with either potassium ion or noradrenaline. The
      relaxation was concentration-dependent, occurring at concentrations from 10(-3)
      to 10(-1) M. The relaxation of rabbit aortic rings (preconstricted with
      noradrenaline) was unaffected by pre-treatment with atropine, propranolol,
      cimetidine, indomethacin, or methylene blue. Endothelial stripping with Triton X
      100, sufficient to completely abolish acetylcholine-induced relaxation, also had
      little effect on methylmethacrylate-induced relaxation. Methylmethacrylate
      produced direct relaxation of rabbit aortic rings constricted with either
      potassium or noradrenaline in calcium-deficient media, and inhibited subsequent
      calcium-induced constriction. These results suggest that methylmethacrylate
      monomer may interfere with intracellular and extracellular calcium mobilization
      and excitation/contraction coupling in vascular smooth muscle. The direct
      relaxation of venous and arterial smooth muscle produced by methylmethacrylate
      monomer may contribute in part to the hypotension that can occur when acrylic
      bone cement is employed during orthopedic procedures.

PMID- 7572022
TI  - Hemodynamic predictors of atrial fibrillation or flutter after coronary artery
      bypass grafting.
AB  - The cumulated incidence of atrial fibrillation or flutter after coronary artery
      bypass grafting is 30%. The causes of these arrhythmias have not yet been
      sufficiently identified. We therefore undertook the present study to analyze the
      possible association of hemodynamic function during the various phases of
      coronary artery bypass grafting and the later development of atrial
      fibrillation/flutter. Hemodynamic function was measured with a pulmonary artery
      catheter in 120 consecutive patients undergoing elective coronary artery bypass
      surgery. Thirty-five (29%) of the patients developed atrial fibrillation/flutter.
      Logistic regression analysis identified independent predictors of atrial
      fibrillation/flutter. After induction of general anesthesia, the relative risk
      (95% confidence interval) of older age was 1.09/year (1.03-1.16), and the
      reduction in relative risk by an increase in left ventricular stroke work was
      0.96/gm (0.93-0.99). After weaning from the extracorporeal circulation the
      independent significant predictors were age, relative risk 1.07/year (1.01-1.13),
      and increased central venous pressure, relative risk 1.12/mm Hg (1.00-1.26). At
      the time of admission to the intensive care unit, the relative risk of age was
      1.10/year (1.03-1.18), and the relative risk of an increased central venous
      pressure was 1.26/mm Hg (1.06-1.49). However, the best prediction model
      (prediction after induction of general anesthesia) only provided a median
      predicted probability of atrial fibrillation/flutter of 0.37 for the patients who
      had atrial fibrillation/flutter, and a median predicted probability of atrial
      fibrillation/flutter of 0.20 for the patients without these arrhythmias. We
      identified possible hemodynamic predictors of atrial fibrillation/flutter after
      coronary bypass surgery, but the use of a risk stratification for development of
      atrial fibrillation/flutter based on hemodynamic function cannot be recommended.

PMID- 7572023
TI  - Effects of heparin on the inhibitory action of protamine on endothelium-mediated
      vasorelaxation.
AB  - The precise mechanism(s) of inhibitory action of protamine on endothelium
      mediated vasorelaxation has not been fully elucidated. In addition, no
      information is available regarding the effects of a heparin-protamine complex on
      the endothelium-mediated relaxation. Employing isometric tension recording
      methods, we studied the effects of heparin, an anionic substance, on the
      protamine-induced inhibition of acetylcholine (ACh)-induced vasorelaxation in
      isolated rabbit small mesenteric artery. Protamine (> or = 50 micrograms/ml)
      inhibited ACh (0.03-10 microM)-induced relaxation under a norepinephrine (10
      microM)-stimulated condition (P < 0.05). The ACh relaxation, even 20 min after
      washout of protamine (150 micrograms/ml), was still significantly inhibited as
      compared to the control (before protamine) ACh relaxation, and further, it was
      not significantly different from the ACh relaxation maximally inhibited in the
      presence of protamine. Preapplication of heparin (700 U/ml) almost abolished the
      protamine inhibition (50 & 150 micrograms/ml) of the ACh relaxation. However,
      heparin (700 U/ml), applied on washout of protamine (150 micrograms/ml), had no
      effect on the prolonged protamine inhibition. In conclusion, a heparin-protamine
      complex had no direct effect on the endothelium-mediated relaxation, and the
      inhibitory action of protamine on the endothelium-mediated relaxation might be
      due to its polycationic property. The prolongation of protamine inhibition and
      the lack of effects of heparin on the prolonged protamine inhibition may suggest
      a toxic effect of protamine on the endothelium.

PMID- 7572025
TI  - Volume replacement during cardiac surgery-influence on microcirculation.

PMID- 7572024
TI  - Adenosine for per-operative blood pressure control in an infant with
      neuroblastoma.
AB  - We describe a child with a localised pelvic neuroblastoma and a hypertensive
      crisis during the first weeks of life due to elevated systemic norepinephrine of
      tumoural origin. In spite of treatment with high doses of alpha-blockers, blood
      pressure did not respond fully and the boy had a very unstable circulation.
      Surgery was performed at one month of age. Adenosine, a potent short-acting
      vasodilator, was used for peroperative blood pressure control to protect the
      patient from an uncontrolled hypertensive crisis. During tumour manipulation the
      child became hypertensive with systolic pressure exceeding 130 mm Hg and
      adenosine infusion (100 micrograms.kg-1.min-1) was started with a prompt
      normalisation of the blood pressure. Adenosine infusion could be discontinued
      after tumour removal. Norepinephrine, dopamine, homovanillic acid and
      vanillylmandelic acid in urine were elevated preoperatively and normalised at
      follow up. Plasma concentrations of norepinephrine and dopamine were elevated
      preoperatively. Norepinephrine increased during hypertension due to tumour
      manipulation. Plasma neuropeptide Y increased during tumour manipulation but
      still within the normal range for infants. It is concluded that adenosine can be
      used peroperatively in children with severe hypertension and in this case no
      adverse effects of adenosine were noted. Furthermore, tumour synthesis and
      systemic release of norepinephrine, but not neuropeptide Y, contributed to
      hypertension in this child with neuroblastoma.

PMID- 7572026
TI  - Transition from lacunar to villous stage of implantation in the macaque,
      including establishment of the trophoblastic shell.
AB  - Adhesion of trophoblast of the blastocyst to and penetration into the uterine
      epithelium, invasion into the maternal vessels and endometrial stroma, and
      establishment of the basic organization of the placenta all occur within the
      first week following the initiation of implantation in the human, macaques and
      several other primates. The cellular rearrangements and interactions of
      trophoblast with endometrial epithelial cells and stroma were studied during this
      preiimplantation stage in macaques. At the early lacunar stage, 1-2 days after
      the initiation of implantation, both cytotrophoblast and syncytial trophoblast
      can be found at the maternal surface of lacunae. As the lacunar stage advances,
      both syncytial trophoblast and cytotrophoblast are found throughout the
      implantation site including in septae partitioning lacunae, but syncytial
      trophoblast lines most of the lacunae and forms the confluence with the maternal
      vessels. Indentations of fetal mesenchyme and accumulation of cytotrophoblast
      cells within the septae occur rapidly. Over a period of about 2 days, clusters of
      cytotrophoblast cells pass beyond the syncytial trophoblast at the maternal
      surface as the anchoring villi, establishing the trophoblastic shell. The
      bypassing of epithelial plaque cells by cytotrophoblast cells and elimination of
      stromal matrix between such clusters verifies that this is a progressive invasion
      rather than simply superficial growth. Concomitant with establishment of the
      trophoblastic shell there is extravasation of blood, necrosis of plaque cells,
      and massive invasion of vessels by cytotrophoblast resulting in a necrotic zone
      between the trophoblastic shell and endometrium. It is concluded that only in the
      brief period of time of establishment of the trophoblastic shell is the full
      invasive potential of cytotrophoblast realized and that only at this stage does
      cytotrophoblast demonstrate the type of invasive and migratory behavior which has
      been achieved with isolated human cytotrophoblast cells in vitro.

PMID- 7572027
TI  - Studies of hemidesmosomes in human amnion: the use of a detergent extraction
      protocol for compositional and ultrastructural analysis and preparation of a
      hemidesmosome-enriched fraction from tissue.
AB  - A method is described for the sequential detergent and high ionic strength
      extraction of human amnion with the progressive enrichment of the intermediate
      filament (IF) cytoskeleton and its associated structures including hemidesmosomes
      (HD). TEM of the extracted epithelium in situ reveals IF bundles beneath the
      apical cell surface, around the nucleus and at the lateral edges of the cells
      where association with desmosomes occurs. IF bundles are also very prominent
      within basal cell processes where they loop through the cytoplasm adjacent to the
      HDs. A novel connecting filament network is observed running between the IFs and
      the hemidesmosomal dense plaque. The adjacent IF network contains both
      cytokeratin and vimentin, the latter revealed much more fully as a result of the
      extraction protocol. The hemidesmosomal plasma membrane contains integrin
      subunits alpha 6 and beta 4 and these are quantitatively retained as the basal
      cell surface during extraction, while nonjunctional plasma membrane is
      solubilised. Integrin beta 1 is found at the basolateral cell surface but, like
      actin, is extracted quantitatively and is not present in HDs. The extracted
      epithelial cells may be recovered by scraping and the IF network depolymerised to
      produce a particulate fraction containing short residual IFs, associated thin
      filaments and plaque material. This fraction contains immunoreactive cytokeratin
      and vimentin. Integrin alpha 6 beta 4 has been used as a biochemical criterion of
      the presence of HD material in the fraction. Both subunits are highly enriched.
      The fraction also contains the hemidesmosomal components HD1, BP230 and BP180.
      This method is likely to be useful in further characterisation of the HD.

PMID- 7572028
TI  - Differential expression of CD44 in rabbit uterine epithelium during early
      pregnancy.
AB  - The expression of the cell surface glycoprotein CD44 was monitored in rabbit
      endometrium during early pregnancy and pseudopregnancy by immunohistochemistry.
      The epitope was not detected in the uterine epithelium of nonpregnant doses; in
      pseudopregnant animals it was expressed only weakly and late, most clearly
      detectable at the last stage investigated, i.e. on day 10. During pregnancy,
      however, CD44 was expressed more strongly in the epithelium starting on day 6,
      i.e. shortly before embryo implantation (day 7). Northern blot analysis confirmed
      this increase in expression. Immunohistochemically, CD44 expression peaked around
      days 8 and 9 of pregnancy and was generally localized on the lateral cell
      membranes of uterine epithelium, but not on basal or apical membranes. The
      staining pattern was similar on all major mucosal folds in that the signal was
      most intense in the luminalmost parts and slightly less in the middle of these
      folds. The intensity was gradually reduced towards the depth of the crypts with
      their deepest parts being negative. At day 10 of pregnancy the intensity of
      staining was clearly reduced in all parts of the epithelium that had been
      positive before. Fusion of epithelial cells, a characteristic phenomenon in
      pregnant rabbit uteri, which is particularly widespread in the implantation
      chamber, was accompanied with abolishment of CD44 expression. While stromal cells
      in general showed only a weak reaction, some individual cells in the stroma were
      always strongly positive (numbers increased after implantation). The trophoblast
      only occasionally exhibited some faint cellular staining in cytotrophoblast as
      well as in syncytiotrophoblast. These data show that CD44 is expressed in rabbit
      uterine epithelium during the periimplantation phase, and that its expression
      appears to be triggered by embryonic signalling and may be relevant for
      implantation.

PMID- 7572029
TI  - Mammary phenotypic expression induced in epidermal cells by embryonic mammary
      mesenchyme.
AB  - The goal of this research was to establish methods for inducing mammary
      epithelial differentiation from nonmammary epithelium. For this purpose, mid
      ventral or dorsal epidermis (skin epithelium; SKE) from 13-day rat or mouse
      embryos was associated with 13-day embryonic mouse mammary mesenchyme (mammary
      gland mesenchyme; MGM) (mouse MGM+rat or mouse SKE). The resultant MGM+SKE
      recombinants as well as controls (homotypic mouse mammary recombinants, homotypic
      mouse skin recombinants and mouse mammary mesenchyme by itself) were grafted
      under the renal capsule of syngeneic or athymic female nude mouse hosts. Most
      female hosts were induced to undergo lactogenesis by grafting an adult pituitary
      which elicited a state of hyperprolactinemia. Tissue recombinants of mouse
      MGM+rat or mouse SKE grown for 1 month in vivo formed a hair-bearing keratinized
      skin from which mammary ductal structures extended into the mesenchyme. The ducts
      were composed of columnar luminal epithelial cells as well as basal, actin
      positive myoepithelial cells. When grown in pituitary-grafted hosts, the ductal
      epithelial cells expressed casein and alpha-lactalbumin as judged by
      immunocytochemistry. The expression of caseins in MGM+SKE recombinants was
      confirmed by Western blot. The epithelial cells in mouse MGM+rat SKE recombinants
      expressing milk proteins were shown to be rat cells while the surrounding
      connective tissue was composed of mouse cells based upon staining with Hoechst
      dye 33258. Using mammary-specific markers, these studies confirmed the earlier
      morphological studies of Propper and unequivocally demonstrated for the first
      time that embryonic mammary mesenchyme can induce morphological and functional
      mammary differentiation from nonmammary epithelium.

PMID- 7572031
TI  - Three-dimensional architecture of collagen fibrils in the mouse corpus cavernosum
      penis.
AB  - The three-dimensional architecture of the collagen fibrils in the corpus
      cavernosum penis of the mouse was studied after digestion of cellular and some
      extracellular elements by NaOH. The tunica albuginea was made up of undulating
      bundles of collagen fibrils which were arranged in outer longitudinal and inner
      circular layers. In both layers, several bundles were successively stacked to
      show the conspicuous lamellar arrangement. On the outer surface of the tunica,
      the collagen fibrils were interwoven like lacework. The trabecula appeared as a
      group of collagen bundles which extended from the inner circular layer of the
      tunica and showed a wavy arrangement. The grouped bundles in the trabecula were
      covered with a delicate sheath of collagen fibrils. These architectural features
      of the collagen fibrils appear to be related to fluctuations in the diameter and
      shape of the corpus during erection and detumescence.

PMID- 7572030
TI  - Adhesion and fusion of ependyma in rat brain.
AB  - Changes of the ependyma of the rat brain from 2 days after birth to 1 year were
      studied. In neonatal rats, the ependyma of the lateral ventricle extended
      medially to cover the hippocampus. The ependyma above the hippocampus disappeared
      with age in two ways: (1) a zipper-like withdrawal of the medial portion of the
      ventricle towards the lateral direction, and (2) adhesion and fusion of the
      ependyma in the lateral region. The zipper-like closure and fusion, which
      resulted in disappearance of the ependyma, took place in almost all rats within 2
      or 3 weeks after birth. Initially, ependymal cells retained their cell polarity
      with regular organization at adhesion sites as a two-cell-layer seam.
      Subsequently, their polarity became disorganized in the fusion areas with
      convergence of the two-cell-layer seam into a one-cell-layer seam, followed by
      disruption. The ciliary bundle of individual ependymal cells became randomly
      oriented, sometimes in two or more directions. At the sites where fusion had
      occurred, fragmentary ependymal seams remained detectable (more than 50%) among
      the neuropil even in adults. These ectopic seams often contained cystic ependymal
      cells. In the third ventricle, adhesion was observed but fusion was not. The
      results indicate that adhesion and fusion of the ependyma occur in select areas
      during brain development, during which ependymal cells lose their cell polarity.

PMID- 7572032
TI  - An immunohistochemical study on cutaneous sensory receptors after chronic median
      nerve compression in man.
AB  - Carpal tunnel syndrome represents the most frequent chronic compressive
      neuropathy in man and hence may be investigated as a spontaneous model of
      peripheral nerve damage and repair. In the present report the fate of nerve
      fibers in the digital skin after long-lasting median nerve compression has been
      investigated immunohistochemically in comparison to normal digital skin, with
      special consideration to sensory endings and encapsulated receptors. The presence
      has been documented of the neurospecific marker PGP 9.5, the glia-associated
      protein S-100, and the neuropeptides CGRP and CPON which are mainly associated
      with the sensory and sympathetic nerve fibers respectively. The morphology and
      distribution of nerve fibers and corpuscles appeared comparable to that of normal
      digital skin; a reduction in the density of sensory receptors has, however, been
      observed, although not to the degree that was expected to explain the clinical
      deficits. It has been also demonstrated that at least part of the CGRP-containing
      sensory and CPON-containing sympathetic axons may survive unaltered even in
      patients with a long clinical history of profound sensorial impairment. An
      apparent discrepancy between the maintenance of nerve fibers and the sensory
      disturbances and the frequent observation of prompt postoperative recovery even
      after years of compression results from this investigation. The correlation of
      immunohistochemical observations and functional scores may not be considered
      conclusive. It must, however, be discussed if the sensorial impairment in this
      syndrome might have, at least in some cases, not only an anatomical but also an
      electrophysiological basis.

PMID- 7572033
TI  - Absence of foramen transversarium in the human atlas vertebra: a case report.
AB  - Anatomical texts allude to many variations in the foramen transversarium of the
      seventh cervical vertebra, including its absence, but absent foramen
      transversarium of the atlas vertebra has not been mentioned. This is the case
      report of an atlas vertebra, the transverse process of which did not exhibit this
      foramen on the left side. However, the groove for the vertebral artery was
      present bilaterally on the posterior arch. The possible factors responsible for
      this interesting variant are discussed.

PMID- 7572035
TI  - Review of research on therapeutic interventions for children with cerebral palsy.
AB  - A computerised search (Med-line) was conducted in March 1994. This review deals
      with the outcome of therapeutic intervention research with cerebral palsied
      children, published in English since 1966. A total of 37 studies were considered
      as therapeutic intervention. Seven studies were classified as equivalent group
      comparison; two were regarded as quasi/non-randomised group comparison; four
      studies were one group before and after treatment comparison research; six
      studies were descriptive; nine studies used single-case approach alone or
      combined with group analysis; six studies were categorised as case-study and
      three studies were regarded as survey in nature. A critical review of the studies
      revealed that the majority were based on a small number of subjects, and on short
      term periods in poorly controlled intervention, often without follow-up. In
      addition, some studies used inappropriate experimental designs and analysis. A
      number of studies reported positive outcome of the therapeutic intervention but
      without experimental control or statistical analysis.

PMID- 7572036
TI  - Palinopsia as sensory epileptic phenomenon.
AB  - Visual perseveration (VP) is defined as persistence or recurrence of visual
      images, when the stimulus is no longer present. We report three patients with
      occipital cortical lesions in the right hemisphere and VP. Electroencephalography
      showed epileptic abnormalities in all cases. In one patient synchronous
      electroencephalic recordings during the onset of palinopsia-a subtype of VP
      revealed, that VP was associated with a clear cut right occipital seizure with a
      secondary diffusion of the discharge over both hemispheres, which has not been
      reported in combination with the onset of palinopsia heretofore. In all three
      patients sensory seizures have to be considered as probable cause of VP.

PMID- 7572034
TI  - A rare case of the posterior inferior cerebellar artery.
AB  - The posterior inferior cerebellar artery (PICA) is normally a branch of the
      vertebral artery. In this rare case, the unilateral left vertebral artery
      continued its course as the left PICA, and an extremely small caliber left
      vertebral artery joined the righ vertebral artery to form the basilar artery.
      This rare feature of the PICA is demonstrated and its relation to neighboring
      structures is discussed. Also, the literature concerning the PICA is reviewed.

PMID- 7572037
TI  - Hypersensitivity of cortical muscarinic receptors in Parkinson's disease
      demonstrated by PET.
AB  - The status of muscarinic receptors (mAChRs) is not clear in Parkinson's disease
      (PD). We measured mAChR binding in the brain of eight patients with PD and eight,
      age-matched, healthy controls by positron emission tomography (PET) and [11C]N
      methyl-4-piperidyl benzilate ([11C]NMPB). PD patients were not demented according
      to DSM III criteria but showed significant frontal lobe dysfunction in the
      Modified Wisconsin Card Sorting Test. A mean K3 value, which is an index of mAChR
      binding calculated by a graphical method, was 20% higher in the frontal cortex of
      PD patients than controls (p < 0.05). Hypersensitivity of mAChRs in the frontal
      cortex of PD patients may be a response to a loss of ascending cholinergic input
      to that region, and may relate to frontal lobe dysfunction in PD.

PMID- 7572039
TI  - Sexual problems in young patients with Parkinson's disease.
AB  - The purpose of this study was to describe sexual function in a representative
      group of young patients with Parkinson's disease (PD). Twenty-five patients (15
      men, 10 women; age range 36-56 yrs) participated in a structured interview on
      sexual function. Forty percent of the men and 70% of the women reported changed
      libido while 33.4% of the men and 80% of the women experienced changed sexual
      activity after onset of PD. A tendency to changes in libido and sexual function
      was seen with increasing time of treatment and advanced Hoehn-Yahr stages. It is
      concluded that changes in libido and sexual function occur more frequently than
      previously reported, especially in women, and more attention should be paid to
      these problems.

PMID- 7572038
TI  - Postural stability differentiates "lower body" from idiopathic parkinsonism.
AB  - INTRODUCTION: Patients with an akinetic Parkinson syndrome of the lower
      extremities and a poor response to L-DOPA have been described as "lower body
      Parkinsonism" (LBP). These patients are characterized by frequent fallings and
      poor balance. METHODS: We have studied body sway with static (force platform) and
      dynamic (Equitest) posturography in 11 LBP patients, 6 of them revealing deep
      white matter lesions on MRI and 10 patients with advanced Parkinson's disease
      (PD) and compared performance with 30 age-matched controls. RESULTS: When
      standing on a fixed support the postural performance of both patient groups lay
      within the normal range. The balance of LBP patients worsened in the static
      testing in the conditions "eyes open on foam" (p < 0.05) and "eyes closed on
      foam" (p < 0.0006, of 11 patients falling), whereas the balance of PD patients
      deteriorated only with "eyes closed on foam" (p < 0.05). Dynamic posturography
      confirmed these results in 6 different sensory conditions, clearly distinguishing
      the more unstable LBP patients from PD patients during "standing, eyes closed,
      foot support sway referenced" (p < 0.005). CONCLUSION: We conclude, that postural
      adjustments in LBP patients are more disturbed than those in PD patients and
      posturography can be an additional tool for the differential diagnosis of
      Parkinson syndromes with gait disorders.

PMID- 7572041
TI  - Variability in cognitive function among persons at high genetic risk of
      Huntington's disease.
AB  - The present study explores cognitive variability and specificity of cognitive
      decline in persons at high genetic risk (AR+ persons) of Huntington's disease
      (HD). Risk status was determined by RFLP markers. Three subgroups were defined
      according to neuropsychological test performance. One subgroup showed a typical
      HD pattern of impairment, a second group selectively impaired verbal memory
      function, and a third group was more heterogeneous. Verbal memory function was
      frequently impaired among AR+ persons. The specificity of verbal memory
      dysfunction was evaluated by using a multivariate statistical clustering
      procedure. While 60% of the AR+ persons were allocated to clusters typical of
      "subcortical dementia", most AR- persons were allocated to a "normal" cluster.
      However, the variability was wide within both the AR+ and AR- group. The
      heterogeneity among AR+ persons was consistent with findings in genetic,
      neuroimaging, and neuropathological studies of HD. Multidisciplinary studies
      should be performed to better understand biological determinants of cognitive
      variability, and to facilitate clinical diagnosis and councelling in individual
      AR+ persons.

PMID- 7572040
TI  - Cognitive function in early adult and adult onset myotonic dystrophy.
AB  - INTRODUCTION: Most studies revealing intellectual deficits in myotonic dystrophy
      (MyD) involved heterogeneous groups of patients with respect to intelligence and
      onset of disease. The present study was undertaken to investigate whether
      patients with early adult and adult MyD show subtle cognitive deficits despite a
      normal intelligence. MATERIALS AND METHODS: We compared 26 MyD patients of normal
      intelligence with mild symptoms and early adult and adult onset to 25 matched
      control subjects (CS) on a range of neuropsychological tests and a number of
      motor tasks of increasing complexity, which required increasing cognitive
      control. RESULTS: The groups did not differ as far as the neuropsychological
      tests were concerned, with the exception of the Stroop Color Word Test. With
      respect to motor performance, the MyD patients were poorer scorers on simple and
      automatic motor tasks than CS, but the difference disappeared as the complexity
      of the tasks increased and required correspondingly more cognitive control.
      CONCLUSION: We found hardly any evidence of cognitive dysfunction in our group of
      MyD patients with early adult and adult onset.

PMID- 7572042
TI  - The snout and palmomental reflexes in HIV disease in Tanzania.
AB  - Following earlier observations on the snout (SR) and palmomental(PMR) reflexes in
      AIDS in Tanzania, a series of 1127 adults, 649 HIV-positive and 478 HIV-negative,
      from 4 groups at different risk of HIV infection were examined neurologically
      between 1987 and 1992. The prevalence of SR and PMR was calculated according to
      HIV status, HIV stage, demographic factors and neurologic findings. In the total
      series of HIV positives the prevalence ranged from SR 39.3% and PMR 22.6% in
      asymptomatic HIV disease to SR 87% and PMR 69% in terminal AIDS. In HIV negatives
      the prevalence of SR was 19.2% and PMR 15.3%, and increased with age. There was
      no relationship with age in the HIV positives and no gender differences. SR and
      PMR were also associated with neuropathy, myelopathy and AIDS dementia complex
      independent of HIV stage. This study shows a strong association between SR and
      PMR and HIV disease in Africa. The prevalence increased with HIV stage and
      related neurological disorders.

PMID- 7572043
TI  - Blink reflex with stimulation of the mental nerve. Methodology, reference values,
      and some clinical vignettes.
AB  - INTRODUCTION: In order to develop an objective electrophysiological method for
      detecting and grading lesions in the inferior alveolar nerve (IAN) and its
      terminal branch, the mental nerve (MN), the normal physiology of the blink reflex
      (BR) with stimulation of the distribution of the MN was evaluated and reference
      values for the MN BR test obtained. MATERIAL AND METHODS: The BR responses to
      electrical stimulation of the distribution of the MN on each side were recorded
      in all 44 healthy adults. The onset latencies and peak-to-peak amplitudes were
      measured and analysed. The effects of the stimulation site, the size of the
      stimulating electrode, and facilitation by eye closure and mathematical task on
      the MN BR responses were tested. RESULTS: A small paediatric stimulating
      electrode was found to be efficient for dermatomal stimulation of the MN
      distribution. The MN BR responses consisted of an ipsilateral late component
      (R2i) on the side of the stimulation and a contralateral component (R2c) with
      similar latency. The latencies were longer and the stimulation thresholds needed
      to evoke a reflex response were higher with stimulation of the MN, when compared
      with the BRs with supraorbital nerve stimulation. Eye closure resulted in
      facilitation of the MN BR in the form of latency shortening, while mathematical
      task did not have any significant effect on the responses. In addition, the test
      was found useful in the diagnosis of iatrogenic IAN lesions after extraction of
      third molars in two patients, and after an orthognathic operation in one patient.
      CONCLUSION: Contrary to some previous reports, constant MN BR responses can be
      elicited in healthy adults, which enables further clinical application of this
      test.

PMID- 7572044
TI  - Cerebrospinal fluid levels of S-100b protein and neuron-specific enolase in
      chronic inflammatory demyelinating polyneuropathy.
AB  - We measured the cerebrospinal fluid (CSF) concentrations of S-100b protein (S
      100b) and neuron-specific enolase (NSE) using enzyme immunoassay methods in 15
      patients with chronic inflammatory demyelinating polyneuropathy (CIDP), other
      three patients with chronic neuropathy with demyelination, eight patients with
      various axonal neuropathies (AN), and 46 controls, to investigate the clinical
      usefulness of the determination of these two specific proteins in these
      neuropathies. S-100b levels were elevated (> the mean +/- 2 SD levels of
      controls) in the majority of patients with clinically progressing CIDP (9/11),
      but not in the patients with AN (0/8). In parallel with the clinical improvement,
      S-100b levels were normalized in patients with CIDP (10/10), though total protein
      levels in the CSF still remained high in some of these patients (5/10). Elevation
      of NSE levels were seldom seen in clinically worsening patients with CIDP (1/11)
      or AN (1/8). Thus our results indicated that the level of S-100b in the CSF may
      be useful to assess the activity of actual disease process in CIDP.

PMID- 7572045
TI  - An abnormal exercise test response revealing a respiratory chain complex III
      deficiency.
AB  - A 29-year-old man with a progressive exertional muscle intolerance since
      childhood was referred for incremental exercise test on a bicycle ergometer. The
      response pattern suggested a mitochondrial myopathy: that is, a greatly reduced
      maximum oxygen consumption with appropriate heart rate increase and an anaerobic
      threshold point reached early. The metabolic investigation in plasma revealed an
      abnormal oxidoreduction status (hyperlactataemia and high lactate/pyruvate ratio)
      at rest and after a carbohydrate rich meal. The histochemical examination of a
      muscle biopsy revealed red granular deposits under the sarcolemma for all type 1
      fibers. Oxypolarographic and enzymological studies of the mitochondrial
      respiratory chain in both isolated mitochondria and muscle homogenate
      demonstrated a marked deficiency of ubiquinol cytochrome c reductase (complex
      III) activity.

PMID- 7572046
TI  - Neurologic manifestations of intravascular lymphomatosis.
AB  - Intravascular lymphomatosis is a rare fatal neoplasm characterized by malignant
      cells of lymphocytic lineage producing vascular occlusions. The cerebral
      vasculature is particularly affected. Two patients seen at our institution
      presented with progressive neurologic deficits including dementia, hemiparesis
      and myelopathy. Review of an additional 64 reported cases with neurologic
      involvement indicates that patients developed intermittent fevers, an
      encephalopathy ranging from acute disorientation to rapidly progressive dementia,
      and focal signs such as hemiparesis and myelopathy. Common laboratory
      abnormalities include elevated cerebrospinal fluid protein and a lymphocytic
      pleocytosis, elevated blood erythrocyte sedimentation rate and serum lactate
      dehydrogenase. Malignant cells are rarely seen in cerebrospinal fluid, blood or
      bone marrow. Neuroimaging is usually abnormal with parenchymal lesions seen on
      cerebral tomography and magnetic resonance imaging along with an occasional
      meningeal pattern of contrast enhancement. Treatment with corticosteroids,
      chemotherapy, radiation therapy, or plasmapheresis provided limited benefit.
      Intravascular lymphomatosis should be considered in the differential diagnosis of
      unexplained progressive encephalopathy with superimposed focal deficits.

PMID- 7572047
TI  - Motor performance in normal pressure hydrocephalus assessed with an
      optoelectronic measurement technique.
AB  - The motor performance of 10 patients with normal pressure hydrocephalus (NPH) was
      clinically assessed with the aid of a computer assisted optoelectronic movement
      analysis system (Mac Reflex). We used the Posturo Locomotion Manual (PLM) method
      that gives a quantitative estimation of the postural, locomotor and manual
      performance in freely moving humans. Measurements were done before intervention,
      after CSF tap test and 3 months post installation of a CSF ventriculo peritoneal
      shunt. Comparison was made to data from 10 matched normal subjects and 10
      patients with Parkinson's disease (PD). Shunt operation of the NPH patients and l
      dopa treatment of the Parkinson patients improved the motor performance to a
      comparable degree. However, while the NPH patients improved the speed in the PLM
      test after the operation, the PD patients also improved the co-ordination after l
      dopa treatment. This could indicate a different mechanism behind the improvement
      of motor performance in NPH and PD after intervention.

PMID- 7572048
TI  - Inhibitory and excitatory amino acids in cerebrospinal fluid of neurolathyrism
      patients, a highly prevalent motorneurone disease.
AB  - Neurolathyrism is caused by overconsumption of seeds containing 3-N-oxalyl-L-2,3
      diaminopropanoic acid (beta-ODAP). Amino acids levels of cerebrospinal fluid
      (CSF) were studied in 50 patients with neurolathyrism and 12 healthy volunteers.
      The levels of excitatory amino acids glutamate and aspartate were 281% and 71%
      respectively of control values. The concentration of inhibitory amino acids
      glycine and taurine were 277% and 198% respectively of the levels in CSF from
      control individuals. There was a significant correlation between the level of
      glycine and the duration of the disease. We also found increased levels of
      threonine, serine and alanine. In contrast to reports on other motor neurone
      diseases where an increase of isoleucine was observed we found a significant
      decrease of isoleucine. The results suggest a disturbance of amino acid
      metabolism due to excitotoxic damages caused by beta-ODAP, a dietary excitatory
      amino acid.

PMID- 7572049
TI  - Primary systemic amyloidosis presenting with polyneuropathy characterized by very
      long survival.
AB  - We report a case of primary systemic amyloidosis associated with IgA monoclonal
      gammopathy presenting with sensorimotor polyneuropathy. For 10 years the
      neurological symptoms were the only clinical manifestation. A great deal of
      therapy was given right from the onset of symptoms and the very long survival of
      the patient may have been due to these efforts.

PMID- 7572050
TI  - Anticardiolipin antibodies (aCL) in patients following acute stroke.

PMID- 7572051
TI  - HTLV-I-like sequence in MS.

PMID- 7572052
TI  - Epileptic seizures, arthrogryposis, and migrational brain disorders: a syndrome?

PMID- 7572053
TI  - Life satisfaction and sexuality in patients operated for epilepsy.
AB  - Changes in sexual behavior are often observed in patients with epilepsy. In order
      to investigate postoperative changes in sexuality and life satisfaction, operated
      and non-operated patients with epilepsy, as well as normal controls, were
      contacted for a survey. The questionnaire included 67 items concerning social
      background, life satisfaction, physical and psychological health, and sexuality
      (sexual desire, sexual contacts, sexual activity, etc). The results showed that
      patients with epilepsy do not rate overall life satisfaction much differently
      from neurologically normal control subjects. Specific questions regarding
      sexuality, revealed a lower sexual drive among the epilepsy patients compared
      with the controls. In most cases, there were no differences between the operated
      and the non-operated patients. Among the operated patients, the seizure-free
      group rated a higher level of life satisfaction and sexuality than the non
      seizure free group.

PMID- 7572054
TI  - Familial mitochondrial encephalomyopathy with deaf-mutism, ophthalmoplegia and
      leukodystrophy.
AB  - We report two sisters (32 and 36 years old) with familial deaf-mutism,
      progressive external ophthalmoplegia, leukodystrophy and mitochondrial myopathy.
      T2-weighted brain MRI demonstrated diffuse symmetrical high intensity areas in
      the white matter. Their muscle biopsies showed ragged-red fibers and cytochrome c
      oxidase (CCO)-negative fibers. CCO activity in biopsied muscle decreased to about
      20% of normal control. They had no deletions of the mitochondrial DNA and no
      point mutations in mitochondrial tRNA. Their brother was diagnosed as having
      Kugelberg-Welander disease, grand mal seizures and urinary dysfunction. Their
      parents and grandparents had consanguinity. Three relatives were found to have
      deaf-mutism without accompanying ophthalmoplegia. This rare combination of
      mitochondrial encephalomyopathy and familial deaf-mutism might be caused by a
      nuclear DNA mutation in these sisters.

PMID- 7572055
TI  - Magnesium concentration in plasma and erythrocytes in MS.
AB  - There are few reports of Mg in MS and none dealing with Mg content in
      erythrocytes. Mg concentration was determined in serum and in erythrocytes with
      the help of a BIOTROL Magnesium Calmagite colorimetric method (average
      sensitivity: 0.194 A per mmol/I) and a Hitachi autoanalyzer in 24 MS patients (7
      men and 17 women, age 29-60; 37 years on average with the duration of the
      disease: 3-19; 11 years on average, at clinical disability stages according to
      the Kurtzke scale: 1-7; 3.2 on average, in remission stage. A statistically
      significant decrease (p < 0.001) of Mg concentration in erythrocytes and no
      changes in plasma of MS patients were found. The results obtained suggest the
      presence of changes in membrane of erythrocytes which could be connected with
      their shorter life and with affection of their function.

PMID- 7572056
TI  - Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy.
AB  - INTRODUCTION: The effect of antiepileptic drugs (AED) on cognitive function was
      studied in 87 patients with epilepsy. MATERIAL AND METHODS: Group A: (n = 52)
      started AED treatment (carbamazepine, oxcarbazepine, sodium-valproate,
      phenobarbital or phenytoin). Group B: (n = 27) had AED monotherapy withdrawn
      (carbamazepine or sodium-valproate). Group C: (n = 8) was switched from phenytoin
      to carbamazepine monotherapy. The patients were tested before and 4 months after
      change of the treatment. RESULTS: In group A the test performances were in
      general unchanged. Patients who had their drug treatment withdrawn (group B) and
      the patients who were switched from phenytoin to carbamazepine (group C) improved
      in single tests. The predominant changes in performance seem to be due to
      practice effect. CONCLUSION: Cognitive functions are only minimally influenced by
      AEDs after short-term treatment whereas there is a slight improvement after
      discontinuation of long-term administration of carbamazepine and valproate. A
      lack of practice effect might be the first indicator of a negative effect of AED
      on cognitive function.

PMID- 7572057
TI  - Lamotrigine: clinical experience in 93 patients with epilepsy.
AB  - This open study reports the use of lamotrigine in 93 adults and children with
      drug resistant epilepsy. Lamotrigine was used predominantly as add-on therapy and
      outcome was assessed by the patient, parents and carers and the physician in
      terms of reduction of seizure frequency, drug side effects, and importantly with
      this drug, improvement in quality of life. Twenty five of the 93 patients (26.9%)
      studied were rendered seizure free with the addition of lamotrigine to their
      therapy. This was especially the case for patients with complex partial seizures,
      generalised seizures secondary to brain damage, primary generalised epilepsy and
      the Lennox Gastaut syndrome. Quality of life improvements were especially
      striking in patients with seizures secondary to brain damage and in the Lennox
      Gastaut Syndrome. Twenty eight patients ceased lamotrigine, 13 due to lack of
      effect and the remainder due to side effects. Lamotrigine is a potentially very
      useful anti-epileptic medication in persons with complex partial seizures, but
      also in primary generalised epilepsy, the Lennox Gastaut syndrome and especially
      in those individuals who have seizures subsequent to brain damage.

PMID- 7572058
TI  - Spectrum of epilepsy in neurocysticercosis: a long-term follow-up of 143
      patients.
AB  - To characterize the clinical profile and the prognostic factors of the epilepsy
      due to parenchymal neurocysticercosis (NCC) 143 patients were analysed. Patients
      (62 men, 81 women) had a mean age at epilepsy onset of 29 years (range 2-71),
      mean epilepsy duration of 16 years (range 1-58) and mean follow-up of 5.2 years.
      Seizures were generalised tonic-clonic (GTC) in 50 patients (35%), simple partial
      (SP) in 66 (46%) and complex partial (CP) in 27 (19%). Epilepsy began as a single
      seizure in 73% and as a cluster of seizures or status epilepticus in 27%.
      Seizures were controlled in 64% of patients. Multivariate analysis revealed that
      significant prognostic factors associated with seizure control were type of
      seizures and age at epilepsy onset. Control is more likely in GTC and SP seizures
      and in patients with a higher age at seizures onset. Our analysis establishes
      that epilepsy due to NCC is a heterogeneous syndrome concerning age and mode of
      onset, seizure type, duration of epilepsy and pattern of evolution probably
      related with different pathogenic mechanisms.

PMID- 7572059
TI  - Role of I-123-iomazenil SPECT imaging in drug resistant epilepsy with complex
      partial seizures.
AB  - Fifteen patients with therapy resistant partial complex seizures with no
      structural lesions were examined interictally with 123-I-IOMAZENIL SPECT for
      measurement of benzodiazepine receptor distribution and with 99m-Tc-HMPAO SPECT
      for measurement of cerebral blood flow distribution. Regional abnormalities were
      correlated with the seizure onset patterns in EEG later recorded with implanted
      subdural strips. SPECT scans were made immediately after and at 1 and 2 h after
      intravenous injection of 123-I-Iomazenil. During that time there was a continuous
      change from an immediate flow-related distribution toward a more specific
      receptor distribution. The decay of radioactivity of I-123 in the brain was
      linear over time. Two patients on benzodiazepine treatment showed much faster
      elimination and showed no focal abnormalities. Eight patients with clear-cut
      unifocal seizure onset showed concordant focal benzodiazepine defects. These
      patients showed a progressive focus/homotopic non-focus enhancement over time
      much larger than the HMPAO scans in the same patients. Also the estimated focal
      area of abnormality was more restricted in the Iomazenil scans than in HMPAO
      scans. Five patients had more complex seizure onset patterns. In these patients a
      mismatch between the locations of abnormalities in Iomazenil and HMPAO scans were
      often found but benzodiazepine receptor abnormalities were more circumscribed
      also in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572061
TI  - Mortality in patients with Parkinson's disease.
AB  - INTRODUCTION: After the introduction of L-dopa the mortality rate in Parkinson's
      disease (PD) patients has changed, but is still higher than in the background
      population. MATERIAL & METHODS: Mortality, age at death and cause of death in a
      group of PD patients compared with the background population were studied. The
      diagnosis on the death certificate were registered. The material consisted of 458
      patients who in a period 1.4.1973-31.10.1991 were registered as having PD.
      RESULTS: Death in the period amounted to 253 patients. Median age of death was
      77.29 years for men and 79.11 years for women. In the background population the
      median age at death was 80.69 years for men and 84.37 years for women. The SMR
      for men was 1.92 and for women 2.47. Infections, in particular lung infections,
      and heart diseases were the most common causes of death. Seventy percent of the
      death certificates had PD as a diagnosis. CONCLUSION: It is likely that several
      factors can influence the changed mortality of PD: more effective treatment,
      changing diagnostic practice, and inter-disease competition.

PMID- 7572060
TI  - Estimate of parkinsonism prevalence through drug prescription histories in the
      Province of Rome, Italy.
AB  - INTRODUCTION: The objective of the study was to estimate the prevalence of
      parkinsonism in the Province of Rome using antiparkinsonian prescription
      histories from 1986 to 1991. METHODS: A subject was defined as a case of
      parkinsonism if he/she had received "specific" and "consistent" antiparkinsonian
      therapy in the study period. RESULTS: In November 1990, 6,572 patients were
      defined as prevalent cases of parkinsonism. The crude prevalence ratio, for the
      total population of the Province of Rome, is 173.5 per 100,000 inhabitants (165.9
      per 100,000 in men and 180.5 per 100,000 in women). The method was validated by
      record-linkage with clinical records of all patients visited during 1990 at the
      Department of Neurological Sciences of the University of Rome "La Sapienza". The
      sensitivity of the prevalence study was 83.6%. CONCLUSIONS: The use of a
      computerized data base of all prescription data, routinely collected for
      administrative purposes, enabled us to obtain a prevalence estimate based on a
      very large population, with low costs and in a relatively short time.

PMID- 7572062
TI  - Occupational environment as risk factor for unemployment in multiple sclerosis.
AB  - INTRODUCTION: Few studies have examined the factors of occupational environment
      related to unemployment in multiple sclerosis (MS). MATERIAL AND METHODS: A case
      control-study was carried out. Cases were patients unemployed for less than five
      years before the study (n = 77); controls were patients currently employed (n =
      94). The odds ratios of the relationship under study adjusted for sex, age,
      disease form and educational level, were estimated. RESULTS: Employment in the
      public sector, sedentary jobs and possibility of obtaining specific improvements
      in the work environment were found to be protective factors, while jobs needing
      force, rigid work schedule, manual precision, frequent moves and a daily work
      duration over 8 h were found as risk factors. Multivariate analyses showed that
      the only remaining factors were public sector jobs as protective factor (OR =
      0.4), and strenuous work as risk factor (OR = 4.5). Factors were slightly
      different in male and female patients. CONCLUSION: This study suggests that
      simple and early changes in the occupational environment could maintain MS
      patients at work.

PMID- 7572063
TI  - Habitual snoring as a risk factor for brain infarction.
AB  - The association of habitual snoring with cerebral ischaemia was studied, in a
      case control-study, in 133 patients aged 45-75 years (103 men and 30 women) and
      133 controls matched for sex and age. Ischaemic stroke was confirmed by brain
      computed tomography or magnetic resonance imaging. History of risk factors,
      especially of snoring and sleeping habits was recorded with structured
      questionnaire during interview. Prevalence of habitual snoring significantly
      differs between patients with stroke and controls: 31/133 (23.3%) vs 11/133
      (8.3%) (Odds ratio 3.4, 95% confidence interval 1.5 to 7.6, p < 0.001). Even
      after adjusting for matching variables and confounding risk factors (arterial
      hypertension, cardiac arrhythmia, and obesity), habitual snoring carries a
      significant risk factor for stroke (odds ratio: 2.9, 95% confidence interval 1.3
      to 6.8 (p = 0.01)). The risk of ischaemic stroke was higher among older male
      patients with arterial hypertension who always snored. Habitual snoring was not
      significantly linked with sleep-related stroke nor with the pathophysiology of
      strokes. Inquiring about habitual snoring should become a routine practice,
      especially among older male patients with arterial hypertension, and specific
      preventive measures should be instituted at an earlier stage.

PMID- 7572065
TI  - Interictal and ictal dipole modelling in patients with refractory partial
      epilepsy.
AB  - Fifteen patients (7 men, 8 women) with mean age of 34 years and mean duration of
      refractory partial seizures of 17 years were included in a presurgical evaluation
      protocol. Neuroimaging (CAT, 1.5 T MR) demonstrated intracranial structural
      lesions (space-occupying: n = 9; atrophic: n = 6) and video-EEG monitoring showed
      complex partial seizures in all patients. Four patients underwent additional
      intracranial EEG monitoring that demonstrated hippocampal seizure onset in all.
      Voltage topography and spatiotemporal dipole mapping of interictal epileptic
      discharges revealed two distinct distinct dipole types. Patients with lesions in
      the medial (and lateral) temporal lobe uniformly presented with a negative
      voltage field with a steep gradient over the inferior temporal area and a stable,
      combined dipole that consisted of a radial and a tangential component with a high
      degree of elevation relative to the axial plane. Patients with extratemporal
      lesions had a more diffuse, less dipolar voltage field and a corresponding dipole
      which was less stable and had a predominant radial component. Dipole modelling of
      epochs of early ictal discharges revealed a striking correspondence with the
      interictal findings in individual patients. Interictal spike voltage topography
      and corresponding dipole mapping provided additional and reliable information
      that was relevant in surgical candidates for refractory partial epilepsy, e.g. by
      suggesting in some patients that the medial temporal structures were not
      primarily involved. Ictal dipole modelling revealed concordant results with
      interictal data. It shows promising but needs further confirmation and validation
      in a larger patient population with intracranial EEG recordings. Despite
      intrinsic limitations, spike voltage topography and dipole mapping contributes to
      a better localisation of the underlying brain source of epileptic discharges.

PMID- 7572064
TI  - Anticardiolipin antibodies in acute non-hemorrhagic stroke seen within six hours
      after onset.
AB  - INTRODUCTION: We have undertaken a prospective study to measure anticardiolipin
      antibodies of IgG isotype within the first few hours of an acute non-hemorrhagic
      stroke. MATERIAL AND METHODS: We have collected blood samples at entry from one
      hundred patients (53 men and 47 women), mean age 67.4 years, referred within 6 h
      of a first-ever non-hemorrhagic stroke, and from an equal number of age- and
      gender-matched control patients. RESULTS: IgG anticardiolipin antibodies were >
      or = 10 GPL in 26 patients and in 5 controls (p < 0.0001, X2 test). After
      logistic regression analysis, increase of IgG anticardiolipin antibodies remained
      independently associated with stroke (p = 0.0034), together with hypertension (p
      = 0.0009) and atrial fibrillation (p = 0.0238). CONCLUSION: Our data suggest that
      the occurrence of elevation of IgG anticardiolipin antibodies in stroke patients
      should antedate stroke onset and might be a risk factor per se.

PMID- 7572066
TI  - Somatosensory evoked potentials in the differential diagnosis between spinal cord
      compression and amyotrophic lateral sclerosis.
AB  - Spinal cord compression (SCC) often presents a similar clinical picture to
      amyotrophic lateral sclerosis (ALS). An early differential diagnosis is important
      because SCC is a potentially treatable clinical disorder. We carried out a
      longitudinal study of 43 patients with an initial diagnosis of ALS, in order to
      ascertain the percentage of patients with SCC, and to evaluate the usefulness of
      somatosensory evoked potentials (SEPs) in early diagnosis. Thirty-three patients
      had a final diagnosis of ALS and 8 of SCC. SEPs central conduction was abnormal
      in 3 ALS and 7 SCC patients, respectively (Fisher exact test, p < 0.05). We
      concluded that SEPs investigation is useful in the differential diagnosis between
      ALS and SCC patients with pure motor signs.

PMID- 7572067
TI  - Reliable disability scale for myasthenia gravis sensitive to clinical changes.
AB  - INTRODUCTION: we developed a disability scale to monitor myasthenia gravis (MG)
      patients, based on degree of function impairment and daily frequency of each
      symptom. MATERIAL & METHODS: the scale was based on standardized questions and
      clinical examination. The scale was administered to 12 patients, one or more
      times, for a total of 22 interviews. Each observation was recorded on videotape
      and reviewed by five independent observers. The ability of our scale to
      discriminate clinical changes was also compared with the Osserman classification.
      RESULTS: our scale showed from substantial to almost perfect inter and
      intraobserver agreement. Our findings showed that clinically relevant changes not
      detected by Osserman staging were disclosed by our scale. CONCLUSION: our scale
      is simple and easy to use in clinical practice. It offers an accurate means of
      evaluating disability in MG patients and may detect clinically relevant changes
      in disability. It would therefore be useful to monitor the effects of therapy.

PMID- 7572068
TI  - Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers.
AB  - Previous studies of cerebral structure in substance abusers yielded controversial
      results, largely due to issues of subject selection and/or limitations of
      experimental techniques. The purpose of the present study was to assess whether
      the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic
      resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared
      with age-matched controls (n = 10). Subjects were male volunteers 21-39 years of
      age. The values of VBR in the polydrug abuse group were not larger than those in
      control group, nor was there any tendency toward relative ventriculomegaly in the
      substance abusers. Therefore, the present findings provide no evidence that
      polysubstance abuse produces abnormalities of gross brain structure in relatively
      young and physically healthy men.

PMID- 7572069
TI  - Motor disturbance during REM sleep in group A xeroderma pigmentosum.
AB  - We investigated motor phenomena during rapid eye movement (REM) sleep in 13
      patients with group A xeroderma pigmentosum aged from 11 to 39 months, and
      compared them with those obtained from 12 age-matched controls. At the time of
      sleep study, they had no abnormality on routine electrophysiological
      examinations. The amount of REM sleep and the incidence of motor phenomena during
      REM sleep in patients were similar to those in age-matched controls. However
      using the newly designated indices, we demonstrated disturbance on both the tonic
      motor inhibition occurring during the whole REM sleep period and the phasic one
      acting simultaneously with horizontal rapid eye movements in these patients.
      Since the motor inhibition during REM sleep is mediated by the subcortical
      structures, our study indicate that these structures are functionally impaired in
      group A xeroderma pigmentosum even during the early stage of the illness.

PMID- 7572070
TI  - Improved detection of auditory P3 abnormality in dementia using a variety of
      stimuli.
AB  - The purpose of this study was to test the improved sensitivity of P3 abnormality
      in the detection of dementia using a variety of auditory stimuli. Improved
      detection was obtained using auditory stimuli that differed in their cognitive
      attributes and by using several P3 measures. These measures included P3 latencies
      and amplitudes relative to pure tone evoked P3s. Fourteen demented patients (mean
      age 79.2 years) and a matched normative group were tested. Abnormality of P3
      latency for pure tone targets was found in ten patients, equivalent to a hit-rate
      of 72%. The hit-rate could be further increased by using phonemically and
      phonetically different types of auditory stimuli, thought to vary in their
      cognitive attributes. These findings underscore the importance of using a variety
      of stimuli in testing demented patients.

PMID- 7572071
TI  - Early features of zidovudine-associated myopathy: histopathological findings and
      clinical correlations.
AB  - Zidovudine-induced myopathy is characterized by reversible muscle weakness,
      wasting, myalgia, fatigue, and elevated creatine kinase (CK). Some zidovudine
      treated patients with normal muscle strength experience excessive fatigue,
      myalgia, or transient mild CK elevations that improve when zidovudine is stopped.
      To determine the cause of these symptoms, we studied 13 physically fit, HIV
      infected men who developed fatigue, myalgia, and reduced endurance, while taking
      zidovudine for a mean period of 20 months (2-39 months), with neurological
      evaluation and muscle biopsy processed for enzyme histochemistry and electron
      microscopy (EM). All subjects had normal muscle strength. In 6 of the 13
      patients, muscle biopsies were normal by enzyme histochemistry. EM, however,
      demonstrated proliferation of normal or abnormal mitochondria, and increased
      amounts of lipid, glycogen, and lipofuscin. Electromyographic (EMG) studies (5/5)
      and serum CK (6/6) were normal. The other 7 individuals had signs of moderate to
      severe mitochondrial abnormalities shown by both light microscopy and EM,
      characterized by severe destruction, vacuolization, and rare paracrystalline
      inclusions. Most had elevated CK (4 out of 7) and normal EMG (5 out of 7). The
      severity of morphological abnormalities did not correlate with duration of HIV
      infection, zidovudine therapy, or zidovudine dosage. We conclude that in
      zidovudine-treated patients, symptoms of fatigue, myalgia, reduced endurance, and
      exercise intolerance represent early signs of zidovudine-induced
      mitochondriotoxicity, which causes an energy shortage within the muscle fibers
      even when muscle strength is still normal. Zidovudine, a DNA chain terminator,
      results in overt myopathy when a critical threshold of molecular, histological,
      and biochemical dysfunction of mitochondria is crossed, which seems to vary
      between individuals.

PMID- 7572072
TI  - Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient.
AB  - Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of
      motor neuron disease (MND) but not in sporadic MND. We report the
      neuropathological findings in a 79-year-old man who died after a 1-year history
      of MND without extrapyramidal features or dementia. There was no family history
      of neurological disease and he had not visited Guam. The spinal cord showed loss
      of anterior horn cells, and skeletal muscle typical changes of denervation. The
      brain appeared macroscopically normal but histology revealed many neurofibrillary
      tangles, particularly in medial temporal lobe structures, insula, nucleus
      basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus.
      Neurofibrillary tangles were not seen in the primary motor cortex, which appeared
      histologically unremarkable. Occasional tangles were present in the substantia
      nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal
      cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S,
      both the intracellular and the extracellular tangles fluoresced strongly under
      ultraviolet light. The intracellular neurofibrillary tangles reacted strongly
      with an antibody to tau protein, and only occasional tangles showed weak
      ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex
      in the areas of neurofibrillary tangle formation. No plaques were present in any
      part of the brain and no A4/beta protein immunoreactivity was detected.
      Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles
      composed of paired helical filaments. The present findings further extend the
      spectrum of diverse neurological disorders associated with neurofibrillary
      tangles.

PMID- 7572073
TI  - Acquired hepatocerebral degeneration in a liver transplant recipient.
AB  - A 47-year-old-man lapsed into coma 12 h after liver transplantation, and remained
      comatose until death 38 days later. Prior to transplantation he had repeated
      episodes of hepatic encephalopathy, but no fixed neurological signs. Autopsy
      revealed typical features of acquired hepatocerebral degeneration with diffuse
      but patchy pseudolaminar cortical necrosis, variable amount of neuronal loss in
      the cerebral cortex, basal ganglia and other areas, and proliferation of
      Alzheimer type II glia. In addition, there was central pontine and extensive
      extrapontine myelinolysis involving the lateral and medical geniculate bodies,
      the thalamus, internal capsule, fornix, mamillothalamic tract, white matter
      bundles in the caudate and pallidum, the oculomotor nuclei and the foliar white
      matter of the cerebellum. The distinction between myelinolytic lesions and
      lesions due to hepatocerebral degeneration was not always clear. Although
      neurological complications and brain lesions are rather common after liver
      transplantation, there have been no reports of acquired hepatocerebral
      degeneration in liver transplant recipients. Our data lend support to the idea
      that a single prolonged comatose episode, due to hepatic dysfunction, may induce
      permanent parenchymal brain damage.

PMID- 7572074
TI  - Age-related decrease of nerve growth factor-like immunoreactivity in the basal
      forebrain of senescence-accelerated mice.
AB  - The senescence-accelerated mouse P10 (SAMP10) is a murine model of accelerated
      senescence characterized by the deterioration of learning and memory with
      advancing age. In the present study, we examined the distribution of nerve growth
      factor (NGF) immunohistochemically in SAMP10 mice and its control strain, SAMR1.
      In both strains, NGF-like immunoreactivity (NGF-IR) was observed in neurons
      throughout the entire forebrain and in glial cells in a particular location. In
      aged SAMP10 mice, each layer of the cerebral cortex retained its NGF-IR, although
      the thickness of the cortical mantle was markedly decreased in comparison with
      younger animals. There was an age-related decline in NGF-IR in the substantia
      innominata of SAMP10 mice at the age of 10 months, when compared to 2-month-old
      SAMP10. These results indicate age-related decrease of NGF in the basal forebrain
      in SAMP10 mice.

PMID- 7572075
TI  - Global brain ischemia and reperfusion: Golgi apparatus ultrastructure in neurons
      selectively vulnerable to death.
AB  - The neocortex and the hippocampus were examined for lipid peroxidation products
      and ultrastructural alterations by fluorescence and electron microscopy,
      respectively, in rats subjected to 10 min of cardiac arrest or 10 min cardiac
      arrest and either 90 or 360 min reperfusion. Lipid peroxidation products were
      observed after 90 min reperfusion in the perikarya and proximal dendrites of
      neocortical pyramidal neurons and in the hippocampal hilar cells and CA1, region;
      the fluorescence was most intense at the base of the apical dendrite, the region
      of the Golgi apparatus. After 90 min of reperfusion, the CA1, showed considerable
      stretches of rough endoplasmic reticulum devoid of ribosomes and the Golgi
      cisternae were shorter and widely dilated. The neocortex showed similar
      endoplasmic reticulum changes, but no significant alterations to the Golgi were
      noted. In addition there were areas where strings of ribosomes appear to be
      detaching from the endoplasmic reticulum. After 360 min reperfusion in both the
      neocortex and the hippocampus, the damage appeared more severe. The Golgi was
      fragmented into vacuoles, membranous whorls had appeared, and dense aggregates of
      smooth vesicles were seen coalescing with each other and the vacuoles. These
      observations suggest that early Golgi involvement is a more important marker of
      lethal injury than ribosome release from the endoplasmic reticulum. The areas of
      disturbed Golgi ultrastructure correspond to those areas that show evidence of
      lipid peroxidation and imply that lipid peroxidation may be causally related to
      the disturbance in Golgi ultrastructure.

PMID- 7572076
TI  - Paired helical filaments and straight tubules in astrocytes: an electron
      microscopic study in dementia of the Alzheimer type.
AB  - Ultrastructural investigation of the hippocampal CA1 and CA4 of nine autopsy
      proven cases of dementia of the Alzheimer type (duration of disease: 3-16 years;
      age: 76-92 years) revealed paired helical filaments (PHFs) and straight tubules
      (STs) in astrocytes of three advanced cases of long duration (> 13 years). The
      PHFs and STs were indistinguishable from those seen in neurons. The abnormal
      glial fibrils were confined to the astrocytic processes that were associated with
      small vessels or, more frequently, with ghost tangles. In both locations the
      astrocytic PHFs and STs were located in the cytoplasm without limiting membranes,
      and were thicker than the straight filaments that composed ghost tangles. These
      findings, combined with the presence of regular constrictions of astrocytic PHFs,
      suggest that abnormal astrocytic fibers are produced by the glial cells, not
      engulfed by them. In addition, the presence of these abnormal glial filaments in
      only advanced, long-duration cases of dementia of the Alzheimer type suggests
      that disease duration has a significant effect upon the formation of these
      astrocytic profiles.

PMID- 7572077
TI  - Epitope expression and hyperphosphorylation of tau protein in corticobasal
      degeneration: differentiation from progressive supranuclear palsy.
AB  - Corticobasal degeneration (CBD) is a rare, progressive neurological disorder
      characterized by widespread neuronal and glial accumulation of abnormal tau
      protein. Using immunohistochemistry we analyzed tau epitope expression and
      phosphorylation state in CBD and compared them to cytoskeletal changes in
      Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Epitopes
      spanning the entire length of the tau protein were present in CBD inclusions. An
      antibody against the alternatively spliced exon 3 did not recognize cytoskeletal
      lesions in CBD, but did in AD and PSP. Tau epitopes from each region of the
      molecule were present in cytoskeletal inclusions in CBD, including gray matter
      astrocytic plaques, gray and white matter threads, and oligodendroglial
      inclusions. As in AD, tau from CBD was highly phosphorylated. Antibodies that
      recognized phosphorylated tau epitopes reacted with material from CBD in a highly
      phosphatase-dependent manner. Again, all types of inclusions contained
      phosphorylated epitopes. We conclude that abnormal tau protein in CBD comprises
      the entire tau molecule and is highly phosphorylated, but is distinguished from
      AD and PSP by the paucity of epitopes contained in the alternatively spliced exon
      3.

PMID- 7572078
TI  - Amyotrophic lateral sclerosis with marked neurological asymmetry:
      clinicopathological study.
AB  - We attempted to correlate the marked neurological asymmetry observed in two
      amyotrophic lateral sclerosis patients with their histopathological lesions.
      Patient 1, a 52-year-old man, developed dysarthria and dysphagia, followed by
      muscle weakness in the left arm and then of the left leg. Patient 2, a 44-year
      old man, developed muscle weakness in the left hand, left leg, tongue with left
      sided predominance, right hand and right leg in that order of progression. Both
      patients exhibited moderate to marked left-sided predominant involvement of the
      lower motor neuron system, accompanied by retained or hyperactive deep tendon
      reflexes on the left side in the early stage of their illness. Most of the
      asymmetry in the lower motor neuron system involvement persisted until the death
      of the patients. Histopathological examinations, including semiquantitative
      analysis, revealed that both patients exhibited left-sided predominant
      degeneration of the lower motor neuron system at those spinal cord levels where
      the neurological asymmetry was of a moderate to marked degree. In addition left
      sided predominant degeneration of the lateral corticospinal tracts was seen in
      both patients and right-sided predominant involvement of Betz cells in the leg
      area of the motor cortex of patient 1. This pattern of both the neurological and
      histopathological asymmetry suggested the probable existence of an intimate
      somatotopically related linkage between the upper motor neuron system
      degeneration and lower motor neuron system degeneration in both patients.

PMID- 7572079
TI  - White matter amyloid in Alzheimer's disease brain.
AB  - Amyloid beta-protein (A beta) deposits in the white matter were investigated by
      the double immunohistochemical staining for A beta and neuritic, glial or
      vascular components. Reactive astroglia and neurite abnormality were absent
      around A beta deposits in the white matter (w-A beta) even those with a core. The
      association of w-A beta with blood vessels was not consistent. Aggregates of
      activated microglia were found to be the sole but a consistent accompaniment of A
      beta deposits even in the absence of other components such as neuron, synapse,
      neurite abnormality and reactive astroglia, as observed in the white matter. This
      suggests that the aggregates of activated microglia most likely represent one of
      the factors promoting the process of A beta deposition.

PMID- 7572081
TI  - Ubiquitin-positive achromatic neurons in corticobasal degeneration.
AB  - A 66-year-old woman presented with an alien limb syndrome without dementia. The
      course of her illness was unremitting and at autopsy 6 years later her diagnosis
      was confirmed as corticobasal degeneration without Alzheimer-type pathology.
      Although the presence of ballooned achromatic cortical neurons and cell loss from
      the substantia nigra distinguishes such patients, the site and density of
      achromatic neurons has not previously been quantified. We show that
      immunohistochemistry for the cell stress protein ubiquitin selectively stains
      these achromatic neurons, whereas they do not stain for abnormally phosphorylated
      tau protein. Phosphorylated neurofilament antibodies recognise both ballooned and
      non-ballooned neurons. In this case, high densities of ubiquitin-positive
      ballooned neurons were found in frontal cortical regions with the highest
      densities in layers V and VI of the anterior cingulate cortex. In addition, high
      densities of ubiquitin-positive ballooned neurons were found in the insular
      cortex, claustrum and amygdala. These results confirm past reports of frontal
      pathology, but show that there is also considerable pathology in insular and
      parahippocampal cortical regions and some subcortical regions. Our findings
      suggest that the distribution and staining characteristics of ballooned neurons
      in corticobasal degeneration may help to differentiate these cases
      pathologically, while the absence of dementia appears to be an important clinical
      criterion.

PMID- 7572080
TI  - Reversibility of neurofilamentous inclusion formation following repeated
      sublethal intracisternal inoculums of AlCl3 in New Zealand white rabbits.
AB  - In this report, we describe the clinical, topographical and immunohistochemical
      characteristics of neurofilament (NF) inclusion formation induced by the
      intracisternal inoculation of young adult New Zealand white rabbits at 28-day
      intervals with 100 micrograms AlCl3 over the course of 267 days. The ability to
      recover following cessation of aluminum exposure has also been assessed. The
      extent of neurofilamentous inclusion formation was proportionate to the
      cumulative amount of AlCl3 inoculated and initially consisted of fusiform axonal
      distention in the ventral spinal cord at day 51 following the initial inoculum.
      Spinal motor neuron perikaryal inclusions and discrete axonal spheroids were
      observed at day 107 and supraspinal neurofilamentous pathology by day 156.
      Perikaryal inclusions were immunoreactive to antibodies recognizing both poorly
      phosphorylated (SMI 32) and more highly phosphorylated high molecular weight NF
      (NFH). In contrast, axonal spheroids were intensely immunoreactive at all stages
      with antibodies recognizing highly phosphorylated NFH and an age-dependent NFH
      phosphorylation state (SMI 34) with only faint SMI 32 immunoreactivity.
      Immunoreactivity to an antibody recognizing ubiquitin-protein conjugates did not
      appear until day 156, whereas inclusions were not immunoreactive to antibodies
      recognizing either phosphatase-dependent or -independent microtubule-associated
      protein tau at any stage. Upon withdrawal from further AlCl3 exposure after
      intervals of 51, 107 or 156 days following the initial inoculum, clinical
      recovery ensued in all rabbits. In all but the most severely affected rabbits,
      perikaryal neurofilamentous inclusions resolved. However, axonal spheroids
      continued to be prominent. These studies demonstrate that the repetitive
      intracisternal inoculation of AlCl3 in New Zealand white rabbits induces a
      reversible process of neurofilamentous inclusion formation that preferentially
      affects motor neurons, and in which recovery will occur in those inclusions
      containing an admixture of both poorly and highly phosphorylated NFH.

PMID- 7572082
TI  - The prenatal age critical for the development of the pontosubicular necrosis.
AB  - Pontosubicular neuronal necrosis is characterized by neuronal karyorrhexis,
      showing a peculiar distribution. In infants delivered at more than 29 gestational
      weeks (GW), neuronal karyorrhexis is restricted to the pons and subiculum, while
      in very premature infants (delivered at less than 28 GW), neurons in other brain
      regions, such as the inferior olivary nucleus, cerebellum, basal ganglia,
      thalamus and cerebral cortex, are also involved. Thus, karyorrhexis is more
      widely distributed in the more immature brain, implicating neuronal maturation as
      one of the pathogenetic factors relevant to this type of neuronal cell death.

PMID- 7572083
TI  - Detection of two transforming growth factor-beta-related morphogens, bone
      morphogenetic proteins-4 and -5, in RNA of multiple sclerosis and Creutzfeldt
      Jakob disease lesions.
AB  - The bone morphogenetic proteins (BMPs) constitute a novel subfamily of the
      transforming growth factor type beta (TGF-beta) supergene family. Here we
      demonstrate, using polymerase chain reaction (PCR) BMP-4 and BMP-5 messages in
      RNA isolated from multiple sclerosis (MS) plaque tissue. This is the first
      demonstration of BMP expression in an inflammatory lesion in general, and in MS
      in particular. However, BMP-4 and BMP-5 messages could be detected in RNA
      isolated from a Morbus Creutzfeldt-Jakob (CJD) lesion. Even in normal brain, RNA
      expression of BMP-4, but not that of BMP-5, was detected. Therefore, BMP-5 gene
      expression seems to be associated with MS and CJD lesions, whereas the BMP-4 gene
      appears to be constitutively expressed in the human brain. As TGF-beta s and BMPs
      are regulators of regenerative processes and contribute to regulation of
      chemoattraction and local immunoreactivity, BMP-4 and BMP-5 might be involved in
      aspects of MS lesion formation unknown so far. PCR analysis of human cell lines
      demonstrate BMP-4 and BMP-5 expression in leukocytic cells, suggesting that
      infiltrating leukocytes contribute at least in part to BMP-4 and BMP-5 mRNAs of
      the MS plaque.

PMID- 7572084
TI  - Prion disease with 144 base pair insertion in a Japanese family line.
AB  - We describe an insert mutation in the prion protein (PrP) gene in a Japanese
      family line that encodes six octapeptide repeats. This is the second report to
      date of an inherited prion disease with a 144-base pair insertion, although the
      order of the repeat sequences differ from that reported for the disease in an
      English family line. The clinical features, like those of the English patients,
      were characterized by a slowly progressive generalized dementia with some
      neurological signs and cortical focal symptoms. Postmortem examination disclosed
      diffuse atrophy of cerebral gray matter and the cerebellar cortex;
      histologically, there were marked patchy and regional neuronal loss with
      astrocytosis in the frontal cortex, amygdala and hippocampus and PrP
      immunoreactive plaques in the molecular layer of the cerebellum. These plaques
      were different from typical kuru plaques. The prion disease in the present
      Japanese family line is compared with that in the English family line.

PMID- 7572085
TI  - Juvenile xanthogranuloma with cutaneous and cerebral manifestations in a young
      infant.
AB  - Juvenile xanthogranuloma is usually a self-limiting disease of the skin.
      Intracranial manifestations are extremely rare. We report the clinico
      pathological features of an 8-month-old boy suffering from a gradually enlarging
      nodule of the chest wall and subsequent epileptic seizures. The subcutaneous
      tumor and a cerebral subcortical tumor of the left temporal lobe were resected.
      The histological appearance of both tumors corresponded to juvenile
      xanthogranuloma and included histiocytes, foamy cells, giant cells, inflammatory
      cells, and collagen-producing fibroblasts showing a storiform pattern.
      Immunohistochemical studies demonstrated positivity of the tumor cells for
      lysozyme, CD68 and myeloid-histiocytic antigen, but not S-100 protein, supporting
      mono-histiocytic differentiation. This case indicates that juvenile
      xanthogranuloma should be considered in the differential diagnosis of
      intracranial "xanthomatous" and histiocytic lesions.

PMID- 7572086
TI  - Coexistence of Pick bodies and atypical Lewy bodies in the locus ceruleus neurons
      of Pick's disease.
AB  - We observed abundant Pick argentophilic inclusion bodies (PBs) as well as some
      atypical Lewy bodies (LBs) in the locus ceruleus (LC) from a patient with Pick's
      disease. In addition, there were a few neurons which contained both PBs and LBs.
      PBs in the LC frequently appeared multiple and had lobulated or irregular shapes,
      though their ultrastructural elements were the same as those of the PBs appearing
      in the cerebral cortex, and consisted of randomly arranged smooth-surfaced
      straight tubules of 15 nm in diameter, mixed with a small number of long-period
      constricted fibrils. The ultrastructure of the LB coexisting with PB was
      identical with that previously reported; a dense core was surrounded by
      concentric layers of radially oriented 10-nm filaments and was clearly
      distinguishable from the PB. Immunohistochemical examination with various
      antibodies related to neurofibrillar pathology demonstrated that anti-tau
      antibodies reacted positively with both PB and the rim portion of LB in the
      present case; an unusual finding for LB. The anti-neurofilament 200-kDa protein
      stained only LBs, even when PBs and LBs coexisted in the same neuron. These
      findings show that two kinds of neuronal fibrillar inclusions, whose underlying
      cytoskeletal abnormalities are thought to be different, can coexist in the same
      neuron. In addition, the formation of multiple, lobulated PBs may suggest some
      particularity of cytoskeletal composition of the LC neurons.

PMID- 7572088
TI  - Human prenatal craniofacial development related to brain development under normal
      and pathologic conditions.
AB  - A survey is given of current knowledge of the interrelationship between facial,
      cranial and brain development in humans. First, normal facial, cranial (mandible,
      maxilla, palatine bone, cranial base, theca cranii, dentition), and brain
      development are described separately. Then, developmental interrelationships are
      illustrated under normal and pathologic conditions (cleft lip and palate,
      holoprosencephaly, anencephaly, amniotic band sequence). New observations are
      described in detail, and references are given to previously published articles. A
      close interconnection exists between the development of the face, the
      craniofacial skeleton, and the brain. This is illustrated by new observations in
      cleft palate fetuses and new theories about the etiology of holoprosencephaly and
      tooth agenesis. The survey focuses, moreover, on the importance of the face and
      the cranial base in endocrine development. Borderlines between face regions and
      cranial regions with different developmental origin are set up for future
      elucidation of the etiology behind syndromes involving the craniofacial regions.

PMID- 7572087
TI  - Homeobox genes and growth factors in regulation of craniofacial and tooth
      morphogenesis.
AB  - Homeobox genes encode a special group of transcription factors that regulate gene
      expression in the developing embryo. The so-called Hox-cluster genes were first
      discovered in the Drosophila (fruit fly). They specify the identity of body
      segments and their patterning along the anteroposterior axis. Other homeobox
      containing genes appear to regulate patterning of the head and face. The function
      of the Msx-1 homeobox gene has been shown to be necessary for tooth development.
      In general, it is thought that special combinations of homeobox genes specify the
      patterning of individual structures. Bone morphogenetic proteins (BMPs) are
      growth factors belonging to the family of transforming growth factor-beta (TGF
      beta). BMPs regulate bone and cartilage development, and individual BMPs have
      been shown to contribute to the shaping of various skeletal elements. BMPs
      regulate bone and dentin formation also postnatally, and they have therapeutic
      potential in reparative osteogenesis and odontogenesis. BMPs also act as
      inductive signals between tissue layers in the embryo, and they regulate the
      expression of several transcription factors, including homeobox-containing genes.
      BMP-4 has been identified as an epithelial inductive signal in tooth development.
      As it is produced by early dental epithelium and regulates tooth-specific gene
      expression in the dental mesenchyme, including Msx-1 expression, it may be an
      important signal for the initiation of tooth development.

PMID- 7572089
TI  - Basic mechanisms in craniofacial growth.
AB  - Bone growth is controlled by growth areas, not active growth centers as stated
      earlier. Conversion of cartilage, sutural deposition, and periosteal remodeling
      are the basic phenomena involved in growth mechanisms. The principles of bone
      growth will result in changes in the size and shape of the mandible and the
      nasomaxillary complex in the three dimensions. The growth rate varies at
      different times during the development of the child. The processes of facial
      growth and changes in the dental arches continue to a much later age than had
      previously been realized. Although our knowledge of craniofacial growth has
      increased during recent times, it is still incomplete with regard to the
      explanation for the regulation of craniofacial growth.

PMID- 7572090
TI  - The role of sutures in normal and abnormal craniofacial growth.
AB  - The paper is a shortened version of a paper read at the symposium on craniofacial
      growth, in which the literature on various aspects of sutures was reviewed.
      Suture development, structure, growth, and closure are covered, and the response
      of sutures to orthopedic forces and their role in craniosynostosis exemplified.
      Rather than being an extensive review, references are included preferably to
      present diversity in results and methods within the subtitle of the symposium,
      'mechanisms and study methods'.

PMID- 7572091
TI  - Basicranial synchondroses and the mandibular condyle in craniofacial growth.
AB  - Basicranial synchondroses are remnants of the fetal chondrocranium and thus
      represent primary cartilage, whereas the chondral part of the mandibular condyle,
      for example, develops unattached to the chondrocranium, as secondary cartilage.
      The two cartilage groups show differences in structure and cell proliferation
      pattern, and yet both are endowed with tissue-separating qualities.

PMID- 7572092
TI  - Some aspects of bone formation and remodeling pertinent to craniofacial
      development and reconstructive treatment.
AB  - Bone formation, modeling, and remodeling occur as physiologic developmental
      growth or healing processes. Bone formation and turnover is an ongoing process
      from early organogenesis to the end of life. The assumption can be made that all
      elements for osteogenesis and resorption are present at any time and can be
      activated given an appropriate environment. Bone is a dynamic tissue that is
      readily influenced by its environment. Recognition of this fact is essential in
      the treatment of dental malocclusions and in reconstruction of jaw, facial, and
      skull deformities. Examples of experimental studies on various environments for
      bone formation and clinical application of the experimental findings are here
      related to treatment of alveolar clefts, bony contour deficiencies, midface
      hypoplasia, skull bone defects, and traumatically or congenitally underdeveloped,
      rudimentary, or missing mandibular condyle/ramus units.

PMID- 7572093
TI  - Normal growth and growth disorders in children.
AB  - Growth in children is influenced by innumerable factors, and to achieve optimal
      final height, the child has to be healthy, its nutrition sufficient, and the
      psychosocial environment stimulating and positive. During the 1st year of life
      nutritional factors and thyroid hormone seem to be the most important regulators
      of growth; during the following years growth hormone increases in importance.
      Puberty and its timing are factors of greatest importance during the 2nd decade
      of life; disturbances in puberty will compromise final height. Increased
      understanding of factors influencing growth and increased access to growth
      hormone and analogs of hormone that influence the timing of puberty have made it
      possible to increase final height in some groups of patients predisposed to short
      stature.

PMID- 7572094
TI  - Endocrine regulation of craniofacial growth.
AB  - This paper presents an updated review of the role of endocrine factors in
      craniofacial and dental development. Some unpublished results of the author's own
      studies are presented. Longitudinal growth studies have shown the similarity of
      facial and somatic growth rates, whereas dental development has been found to be
      independent. The increased therapeutic use of the growth hormone (GH) has focused
      attention on the dental and craniofacial effects of GH. Whereas delayed and
      advanced cranial base and facial growth is obvious in conditions with either lack
      or excess of GH, the effect of GH on the dentition is less clear. Thyroid
      hormones seem to be necessary for the eruptive movement of teeth. Sex steroids
      clearly have an effect on facial and cranial base growth and are also
      odontogenic, but the effects have not been much studied. The growth-inhibiting
      effect of corticosteroids is explained partly by the reduced response of
      cartilage cells to insulin-like growth factor-1. Experimentally, the effect is
      also seen in the condylar cartilage, but clinical studies have not been
      published. In tooth eruption an accelerating effect has been noted in
      experimental animals. The role of androgenic hormones in mandibular growth
      stimulation is discussed.

PMID- 7572095
TI  - Craniocervical junction as a focus for craniofacial growth studies.
AB  - The craniocervical junction is a highly specialized unit simultaneously
      supporting head during movements in all planes and protecting the spinal cord.
      Anatomically, it includes an atlantoaxial complex, part of which embryonically
      arises from the occipital region of the skull. This review deals with the gross
      anatomy, kinematics, and growth reactions associated with functional alteration
      in this complex. Particular attention is paid to the atlas, the connecting
      element between the head and the vertebral column proper. From several studies it
      is concluded that the horizontal growth of the atlas is regulated by
      synchondroseal growth, whereas the vertical growth is determined by appositional
      growth. Some vertebral anomalies and concomitant anomalies of the cranial base
      are reported, to point out the ontogenetic integration between the skull base and
      the craniocervical junction. The high frequencies of atlantal posterior arch
      deficiency in cleft palate patients have led to speculations about common
      etiologic factors in these conditions.

PMID- 7572096
TI  - Growth of the cranial vault: influence of intracranial and extracranial
      pressures.
AB  - The cranial vault is composed of several flat membranous bones whose growth is
      mainly a result of the activity in the interposing sutures. The reactions of the
      calvarium and cranial base to provoke stimuli of the sutures differ depending on
      their developmental stage. In this report the effects of pressure, exerted
      extracranially by means of mechanical forces or intracranially by means of
      hydrodynamic fluctuations, are described.

PMID- 7572097
TI  - Masticatory muscle influence on craniofacial growth.
AB  - The influence of the masticatory muscle function on craniofacial growth has been
      recorded in a series of animal experimental and clinical studies. The common
      characteristic of these investigations is that the elevator muscles of the
      mandible influence the transversal and the vertical dimensions of the face. The
      increased loading of the jaws due to masticatory muscle hyperfunction may lead to
      increased sutural growth and bone apposition, resulting in turn in an increased
      transversal growth of the maxilla and broader bone bases for the dental arches.
      Furthermore, an increase in the function of the masticatory muscles is associated
      with anterior growth rotation pattern of the mandible and with well-developed
      angular, coronoid, and condylar processes.

PMID- 7572098
TI  - Abnormal craniofacial growth.
AB  - Treatment of patients with craniofacial (CF) anomalies necessitates knowledge
      about normal CF growth and how it deviates in the abnormal state. There are
      different basic types of CF anomalies and various kinds of aberrations that
      influence CF development. These factors might help to explain why patients
      display growth variations. The effect of surgery on subsequent development is
      significant, but the heterogeneity among patients with regards to the morphology,
      etiology, and pathogenesis of the anomalies could also explain certain growth
      results. Roentgencephalometric findings related to CF growth in three different
      groups of anomalies are discussed.

PMID- 7572099
TI  - Human sperm reservoirs and Fallopian tube function: a role for the intra-mural
      portion?

PMID- 7572100
TI  - A new symphysis-fundus height growth chart based on a well defined female
      population with ultrasound-dated singleton pregnancies.
AB  - BACKGROUND: The aim was to construct a new symphysis-fundus (SF) height growth
      chart, based on ultrasound-dated singleton pregnancies. METHODS: We made a
      population-based study of all women, from the catchment areas of three district
      antenatal clinics, who registered for antenatal care during 1986. The growth of
      the SF height was measured on 403 women with singleton pregnancies. RESULTS:
      During pregnancy each woman made on average 14.0 (s.d. 2.8) visits to the
      antenatal clinic, where the SF height was measured on average 10.4 (s.d. 2.6)
      times. All but two women had an ultrasound examination. Using proper longitudinal
      methods a new SF height growth chart was constructed. CONCLUSION: The mean values
      of the present curve, based on longitudinal data, were almost identical with the
      mean values of a recently presented curve based on stratified cross-sectional
      data. Both these Swedish studies were population-based and the pregnancies were
      ultrasound-dated.

PMID- 7572101
TI  - The prevalence of red cell antibodies in pregnancy correlated to the outcome of
      the newborn: a 12 year study in central Sweden.
AB  - BACKGROUND: All maternal red cell antibodies found during pregnancy in a 12 year
      period have been compiled. The efficacy of the current antenatal screening and
      management programme has been ascertained by reviewing the outcome of all
      newborns to these immunized mothers. METHOD: Patient selection was carried out by
      computerised searching for all known records of registered antibodies during the
      study period. Each mother's obstetric record and her baby's hospital file was
      studied and relevant clinical treatment and laboratory data on both mother and
      child was recorded and analysed. RESULTS: Eight hundred and twenty-one
      alloantibodies were detected in 629 immunized pregnant women with 753 fetuses. An
      overall antibody incidence of 0.57% was observed which included 373 clinically
      significant antibodies found in 261 mothers (0.24%). Multiple antibodies were
      present in 8.2% of all samples. Anti-D, by itself or in combination with other Rh
      antibodies, caused more severe forms of hemolytic disease of the newborn (HDN)
      with 46% of all Rh-positive babies having phototherapy and 29% having exchange
      transfusion. Three of 18 Fya-positive infants required phototherapy and one
      required exchange transfusion and in the 16 Kell-positive babies, three required
      phototherapy and one required exchange transfusions. CONCLUSIONS: Few antibodies
      to blood group antigens other than those in the Rhesus system were found to cause
      severe HDN. Antibodies that are generally considered non-significant did not
      cause HDN in this study. All antibodies that induced HDN were detected in time so
      that adequate measures could be taken to reduce the effects in the newborn. The
      antenatal screening and management programme currently in use is considered to be
      reliable.

PMID- 7572102
TI  - Severely impaired fetal growth is preceded by maternal hemodynamic maladaptation
      in very early pregnancy.
AB  - OBJECTIVE: To test the hypothesis that in pregnancies complicated by intrauterine
      growth retardation (IUGR) maternal cardiovascular adaptation is already abnormal
      in the first weeks of pregnancy. SETTING: University Hospital Maastricht,
      Maastricht, The Netherlands. SUBJECTS: Fourteen healthy pregnant women, recruited
      from the subfertility clinic. Ten pregnancies were uneventful and four
      pregnancies resulted in the birth of growth retarded infants. METHODS: Maternal
      cardiovascular status was followed longitudinally by combined M-mode and Doppler
      echocardiography. Studies were performed weekly between the fifth and 10th week,
      at 14, 25 and 35 weeks and postpartum. Differences between the two groups were
      analyzed by nonparametric tests. RESULTS: In early pregnancy, the IUGR group
      differed from the normal group by a consistently smaller left atrial diameter and
      a cardiac output that failed to increase. Postpartum the subjects in the IUGR
      group had a significantly smaller left atrial diameter and faster mean
      circumferential fiber shortening. CONCLUSION: Maternal hemodynamic adaptation in
      the first weeks of pregnancy is defective in IUGR pregnancies, presumably
      associated with a concomitant inadequacy of the vascular filling state.

PMID- 7572103
TI  - Cervical fetal fibronectin correlates to cervical ripening.
AB  - AIM OF STUDY: It is well established that the cervical ripeness is of great
      prognostic value at labor induction. The available methods of measuring the
      cervical ripeness are not satisfactory. This study was therefore initiated to
      investigate if there is any correlation between cervical fetal fibronectin and
      cervical ripening at term. METHOD: Three groups were included in this study:
      women with unripe cervices, women with spontaneous cervical ripening and those
      with PGE2-induced cervical ripening. Fetal fibronectin was measured by ELIZA
      after sampling from the cervical canal. RESULTS: The cervical fetal fibronectin
      was low in women with unripe cervices. In women with favorable cervices a ten
      fold higher level was found. The fibronectin level was even higher after PGE2
      induced ripening. CONCLUSION: Conclusively an increased amount of cervical fetal
      fibronectin is registered during the cervical ripening process. A level of > 0.80
      microgram/ml of cervical fetal fibronectin seems to indicate a favorable cervix.

PMID- 7572104
TI  - Breech at term--mode of delivery? A register-based study.
AB  - BACKGROUND: The present study was designed to determine neonatal mortality and
      morbidity in non-malformed singleton term infants delivered in breech
      presentation and identify a possible correlation between outcome on the one hand
      and mode of delivery, parity and birth weight on the other. METHODS: Register
      based cohort study of all (n = 15718) singleton term breech deliveries of non
      malformed infants in Denmark 1982-1990. Process and outcome measures: mode of
      delivery, gestational age, birth weight, congenital malformations, intrapartum
      death, Apgar scores and early neonatal death. RESULTS: A total of 3247 (20.7%)
      term infants were delivered vaginally, 7106 (45.3%) by elective and 5356 (34.1%)
      by emergency cesarean section. Infants delivered vaginally and by emergency
      cesarean section had significantly higher rates of mortality (intrapartum and
      early neonatal death) and morbidity (low Apgar scores) when compared to those
      delivered by elective cesarean section. In vaginal deliveries, parity was not
      correlated with outcome, but infants with a birth weight above 4000 grams had
      significantly higher rates of low Apgar scores. CONCLUSIONS: Register data on
      singleton term breech deliveries imply that vaginal delivery is associated with
      increased mortality and morbidity. However, validation of data and additional
      information from the medical records are needed before a recommendation of
      whether selection of parturients, structure of perinatal care or professional
      skills need to be improved, or all singleton term infants in breech presentation
      should be delivered by cesarean section.

PMID- 7572105
TI  - Simulated intraperitoneal absorption of irrigating fluid.
AB  - BACKGROUND: Intraperitoneal absorption of electrolyte-free irrigating fluid may
      occur secondary to uterine perforation during endometrial resection, but the
      clinical course of this complication is known from only a few case reports.
      METHODS: We studied symptoms, biochemical changes and the kinetics of solute
      equilibration over the peritoneal membrane in 10 healthy awake women who were
      subjected to an experimental absorption situation by receiving an intraperitoneal
      infusion of 25 ml/kg of a solution containing glycine 1.5% and ethanol 1% over 20
      min. We also compared the use of breath ethanol and serum sodium samples to
      indicate the presence of irrigating fluid in the peritoneal cavity. RESULTS: All
      infusions caused lower abdominal pain. The solute gradients between the
      peritoneal pool and plasma were reduced according to mono-exponential functions
      with a half-time of 33 +/- 5 min for ethanol, 92 +/- 9 min for sodium, 103 +/- 9
      min for potassium, and 124 +/- 10 min for amino acids (mean +/- s.e.mean). Twenty
      minutes after infusion, the breath ethanol level reached a plateau which could be
      used to predict the infused volume within +/- 15% of the true value. In contrast,
      the serum sodium concentration decreased slowly and was only 3.0 +/- 0.7 mmol/l
      below baseline at 2 hours after infusion. CONCLUSIONS: The calculated rates of
      transperitoneal solute equilibration can be used to assess the need for
      substitution of electrolytes in patients who absorb irrigating fluid into the
      peritoneal cavity. Measurement of ethanol in the expired breath is more useful
      than serum sodium to indicate the existence of such a pool.

PMID- 7572106
TI  - Oral contraceptives and low back pain. Attitudes among physicians, midwives and
      physiotherapists.
AB  - BACKGROUND: Only few indications have appeared in the literature concerning a
      possible relationship between the use of oral contraceptives and low back pain.
      In our daily work we often meet women who have been recommended to abandon their
      use of oral contraceptives depending on coexisting low back pain. In order to
      assess the opinions of a possible relationship between oral contraceptives and
      low back pain this study was undertaken. METHODS: A validated questionnaire was
      sent out to physicians, physiotherapists and midwives dealing with either
      contraceptive counselling or low back pain. A modified questionnaire was sent to
      medical- and physiotherapist students to assess whether the opinions were a
      result of the education or the working experience. RESULTS: A total of 225
      questionnaires were sent out and 206 (91%) were returned. Sixteen percent thought
      there was a relationship between the use of oral contraceptives and risk of low
      back pain. Thirty percent had seen patients with low back pain that was
      interpreted as being affected by use of oral contraceptives. Twenty-five percent
      recommended at least some patients with low back pain to change their
      contraceptive method. Among the students there was a difference in opinion
      between the first and the last year students indicating that their opinions had
      been influenced by their education. CONCLUSIONS: Evidently many professionals
      dealing with oral contraceptives and low back pain believe that there is a
      relationship between oral contraceptives and low back pain, despite the lack of
      scientific evidence. These recommendations might influence the contraceptive
      safety for the individual woman and the possible relationship between use of oral
      contraceptives and low back pain should therefore be more thoroughly investigated
      before general recommendations are given.

PMID- 7572107
TI  - Recalled menarche in relation to infertility and adult weight and height.
AB  - BACKGROUND: Possible relationships between menarche and fertility and fecundity
      later in life have not been fully clarified. METHODS: A cross-sectional study was
      made in a random sample of 3743 women, aged 15-44 years, in the country of
      Copenhagen; 78% responded. Telephone interviews were made with a sample of the
      non-respondents. RESULTS: Associations were observed between early menarche and
      increased risk of pelvic inflammatory disease (odds ratio 2.4 (1.4-4.1)) and
      spontaneous abortion (OR 3.1 (1.6-5.7)) later in life. On the other hand, no
      association was found with irregular bleedings or amenorrhoea; nor was a
      significant relationship established with fertility or fecundity. Late menarche
      was associated with underweight (OR 3.1 (1.4-6.9)), and early menarche with
      excess weight (OR 5.0 (2.4-10.6)). A significant positive correlation (R = 0.17)
      was found between menarcheal age and final body height. CONCLUSIONS: Menarche was
      not associated with fertility or fecundity. Early menarche was associated with
      pelvic inflammatory disease and spontaneous abortion. Menarche showed
      relationships with weight and height.

PMID- 7572108
TI  - Nodal immune reactivity in FIGO (International Federation of Gyn-Ob) Stage I
      endometrial carcinoma: relationship with myometrial invasion.
AB  - BACKGROUND: To evaluate T lymphocyte subsets in pelvic and paraortic lymph nodes,
      in patients with FIGO stage I endometrial carcinoma at different degrees of
      myometrial invasion and with lymphovascular space invasion. The aim was to define
      an eventual modulation of regional immune reactivity useful in the therapeutic
      approach of the disease. METHODS: Twenty-two women with FIGO stage I endometroid
      adenocarcinoma were consecutively recruited and selected for immunological study.
      All the patients underwent primary surgery characterized by radical hysterectomy
      (Piver's type III) with bilateral salpingo-oophorectomy and systematic pelvic
      plus paraaortic lymphadenectomy. Lymphocyte tipization was performed by Beckton
      Dickinson monoclonal antibodies (CD4, CD8, CD56 and CD16) immunohistochemically
      in frozen-sections (immune assay on lymph nodes). For statistical evaluations.
      Student's t test and one way analysis of variance were used. RESULTS:
      Significantly higher percentages of CD4+ lymphocytes were found in pelvic than in
      paraaortic lymph nodes; however, by analyzing T lymphocyte content in the
      different pelvic nodal groups, we also observed significantly higher percentages
      of CD16+ and CD56+ cells in obturator nodes when compared to iliac stations. A
      significant increase of CD16+ and CD56+ cell percentages was then defined with
      respect to myometrial involvement and lymphovascular space invasion, in pelvic
      nodes. CONCLUSIONS: From our results, we could not define any clinical importance
      of nodal lymphocyte distribution in patients with early stage endometrial
      carcinoma; however, the observed nodal immune reactivity in presence of
      myometrial invasion seems interesting, with or without lymph vascular space
      involvement as possible expression of neoplastic systemic diffusion.

PMID- 7572110
TI  - Diagnosis of pelvic masses with transabdominal color Doppler, CA 125 and
      ultrasonography.
AB  - BACKGROUND: The objective of this study was to test the accuracy of
      transabdominal color Doppler imaging in the prediction of malignancy of adnexal
      tumors when integrated in combination with CA 125 levels and two-dimensional
      ultrasound. METHODS: We considered 129 consecutive patients with a suspected
      adnexal mass at clinical examination and transabdominal and transvaginal two
      dimensional ultrasound. Serum CA 125 was measured in all cases. All the patients
      underwent color Doppler imaging to measure the Resistance index of the tumor
      associated blood flow profile and then surgery and histologic diagnosis. RESULTS:
      The median age of the patients was 44 years (range 12-91), 64.3% were
      premenopausal and the prevalence of malignancy was 28.7%. The sensitivity of
      color Doppler mapping was 75.7%, specificity 71.7%, positive predictive value
      68.3% and negative predictive value 93.0%, compared with 75.7%, 68.5%, 49.1% and
      87.5% for CA 125 and 83.8%, 83.7%, 67.4% and 92.8% for two-dimensional
      ultrasound. Blood flow was undetectable by color Doppler imaging in 17 of the 129
      cases (13.2%). In 55 patients with three concordant tests, the positive and
      negative predictive values were 100%. When CA 125 values and two dimensional
      ultrasound results were discordant (35 patients), the color Doppler diagnosis was
      correct in 88.6% of the cases (93% in premenopausal women). CONCLUSION: Color
      Doppler imaging alone is not better than two-dimensional ultrasound in predicting
      malignancy of pelvic masses. Its use together with CA 125 and two-dimensional
      ultrasound may improve the accuracy of predictions when the three tests are
      concordant or when the other two are discordant.

PMID- 7572111
TI  - Adjuvant chemotherapy in stage IB neuroendocrine small cell carcinoma of the
      cervix.
AB  - BACKGROUND: Neuroendocrine small cell carcinoma of the cervix is a very rare and
      aggressive tumor which tends to metastasize early. This tumor is similar
      histologically to small cell carcinoma of the lung. Conventional treatment with
      surgery and/or radiation therapy has not been successful and has prompted the use
      of adjuvant chemotherapy regimens similar to those used for small cell carcinoma
      of the lung. METHODS: Three patients with Stage IB neuroendocrine small cell
      carcinoma of the cervix treated with postoperative adjuvant chemotherapy
      consisting of cisplatinum and VP-16, were identified. Analysis of the outcome of
      these three patients and a review of the current literature were performed.
      RESULTS: Median survival was 28 months. Two patients received pelvic radiation
      therapy, one due to positive surgical margins and the other due to recurrent
      disease. Currently two patients are alive and free of disease at 17 and 61
      months. The third patient developed hepatic and pelvic recurrence and died 30
      months after her presentation and 18 months after recurrence. CONCLUSION: The
      outcome of our three patients and eight similar cases in the literature suggest
      an improved survival rate with adjuvant chemotherapy compared to conventional
      treatment with surgery and or radiation therapy.

PMID- 7572109
TI  - The cervical smear record: its relevance to the subsequent development of
      cervical neoplasia.
AB  - BACKGROUND: Our aim was to investigate the previous smear history in women with
      cervical intraepithelial neoplasia grade 1-3 or squamous carcinoma and define its
      relevance to the lesion present in 1989. METHODS: All 850 women with a laboratory
      record of cervical intraepithelial neoplasia or cervical squamous carcinoma in
      1989 were studied. We retrieved their cytological and histological cervical
      diagnoses for the period 1981 to 1992 from the laboratory files. On this basis we
      assessed their previous smear history and short term clinical outcome. RESULTS:
      Half the women had a negative record prior to 1989, irrespective of the grade of
      their lesion in that year. Cervical intraepithelial neoplasia grade 1 had
      previously been found in 16%, grade 2 in 10%, and grade 3 in 7%. These levels
      were not related to the grade present in '89, but as in those with a negative
      record, were proportional to the number of women examined, and thus reflect the
      frequency of such lesions in the screened population in general. In all, 310 were
      treated operatively for cervical intraepithelial neoplasia grade 3 following
      abnormal findings in 1989. In such cases abnormal findings were also common in
      '88, although 45% of them still had a negative smear history. The group with no
      previous record, i.e. unscreened, contained significantly more invasive cases.
      CONCLUSIONS: In women with cervical intraepithelial neoplasia in 1989, their
      previous smear history did not indicate the grade of lesion present. The
      relevance of their previous abnormal slides to that lesion is thus questionable.
      The findings, however, suggest that progressive lesions may be acute in origin,
      superimposed in some cases on a history of similar morphological abnormalities.

PMID- 7572112
TI  - Splenectomy for isolated splenic metastasis from endometrial carcinoma.

PMID- 7572113
TI  - Hemangiopericytoma of the uterus: an unusual cause of the postmenopausal
      metrorrhagia.

PMID- 7572114
TI  - Coexistence of bilateral tubal and intrauterine pregnancy.

PMID- 7572115
TI  - Successful treatment of a combined interstitial and intrauterine pregnancy after
      tubal embryo transfer (TET).

PMID- 7572116
TI  - Deferoxamine treatment for acute iron intoxication in pregnancy.

PMID- 7572118
TI  - Doppler ultrasound findings in female infertility. With special reference to
      pelvic inflammatory disease and endocrinological factors.

PMID- 7572117
TI  - Imaging techniques in an eclamptic patient-demonstration of spinal cord lesion
      using MRI.

PMID- 7572119
TI  - Pre versus post-operative radiotherapy of resectable squamous cell carcinoma of
      the head and neck.
AB  - The literature on pre-operative radiotherapy (RT) vs. post-operative RT in
      patients with advanced, resectable squamous cell carcinoma of the head and neck
      is reviewed and the theoretical arguments for and against the two different
      modalities discussed. It was possible to identify eleven reports published during
      the last four decades (1965-91) evaluating different aspects of pre- vs. post
      operative RT given at comparable dose levels. Two reports were of prospective,
      randomised clinical studies and nine of retrospective comparisons. Together, the
      eleven studies comprised 1,358 patients (326 in prospective studies). The bulk of
      the evidence clearly suggests post-operative loco-regional control to be superior
      to pre-operative RT. However, this seems to be offset by the subsequent
      development of distant metastases or metachronous tumours.

PMID- 7572120
TI  - Vestibulo-ocular reflex (VOR) biases in normal subjects and patients with
      compensated vestibular loss.
AB  - The properties of the vestibulo-ocular reflex (VOR) were examined during
      sinusoidal passive head rotation in the dark at 1/6 Hz, in 9 normal subjects and
      14 unilateral vestibular patients. Rotation speeds ranged from 90 to 180
      degrees/s. The bias (offset of slow-phase velocity from zero) and gain in the VOR
      were estimated by using a polynomial (cubic) fit between head and slow-phase eye
      velocity, thereby allowing for possible non-linearities in the reflex. The gain
      in the VOR in this context refers to the linear components of the fit, and so
      predicts sensitivity only at low head velocities. The aim of the study was to
      verify previous theoretical predictions that VOR bias could vary with the
      rotation parameters, that this bias could be used to detect the side of a
      vestibular lesion even at low frequency rotation, and make non-linearities more
      obvious. Confirming these predictions, the VOR bias in a given test is never
      equal to any spontaneous nystagmus, even if present before rotation. The range of
      values for the gain in the VOR (as defined above) in normals and compensated
      unilateral vestibular patients overlap, so that they cannot be statistically
      separated into two response sets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572121
TI  - Caloric evoked motile responses of mammalian vestibular sensory cells.
AB  - Evokation of caloric nystagmus in microgravity argues against thermal convection
      as a sufficient explanation for a caloric nystagmic response. By contrast,
      caloric nystagmus observed in weightlessness suggests a gravity independent
      mechanism. Here we demonstrate that direct caloric stimulation of isolated living
      vestibular hair cells from the guinea pig evoked mechanical responses of the
      sensory cells. Heating of the mechanoreceptor cells from 37 degrees C to 42
      degrees C resulted in elongation cooling of the cells from 37 degrees C to 30
      degrees C induced shortening of vestibular hair cells. The observed mechanism
      might contribute to the caloric evokation of a nystagmus both on earth and in
      orbit.

PMID- 7572122
TI  - Effect of lidocaine injection of EOAE in patients with tinnitus.
AB  - In the present study, evoked otoacoustic emissions (EOAEs) were measured in 30
      patients with tinnitus before and after intravenous lidocaine injection (1
      mg/kg). For EOAE recordings, 1 kHz tone burst stimuli were used. Intravenous
      lidocaine injection resulted in suppression of tinnitus in 22 (73%) ears, and
      changes of EOAE amplitude (increase or decrease) in 18 (60%) ears. Of the 18 ears
      with EOAE amplitude changes, tinnitus disappeared or decreased in 17 (94%) ears.
      In 12 ears without changes of EOAE amplitude, tinnitus was suppressed in only 5
      (42%). Changes in latency were not detected in any of the ears. These results
      indicate that there is a relationship between the effect of lidocaine in tinnitus
      suppression and changes in cochlear micromechanics caused by lidocaine.

PMID- 7572123
TI  - Studies of currently used and experimental cochlear implants.
AB  - Since 1987 we have inserted multichannel cochlear implants in 60 patients with
      severe hearing impairment. The surgical procedures were not very difficult, and
      few postoperative complications were encountered. Postoperative speech
      recognition by every patients was satisfactory. Nevertheless, some patients
      complained about their hearing in a noisy environment, or while listening to
      either TV or music. Consequently, cochlear implants needs further improvement. To
      improve speech recognition ability, a newly developed experimental system was
      constructed. Judging from the electrode activation pattern, the new system
      extracted the features of consonants more successfully than the present system.
      However, when this new system was installed in cochlear implant patients, no
      significant improvement in consonant recognition was obtained.

PMID- 7572124
TI  - Expression of Na, K-ATPase alpha and beta isoforms in the neonatal rat cochlea.
AB  - The postnatal expression of five Na, K-ATPase alpha (alpha 1, alpha 2, alpha 3)
      and beta (beta 1, beta 2) subunit isoforms in the rat cochlea was investigated by
      immunocytochemistry. High levels of expression of the alpha 1 and beta 2 isoforms
      were observed in stria vascularis (SV) at all developmental stages. alpha 1 and
      beta 1 isoforms showed a distinct time-dependent developmental expression pattern
      in tissues of the spiral ligament (SL) and spiral limbus (SLi). Limited,
      temporary expression of alpha 2 and alpha 3 subunit isoforms were found in SV and
      SL. Expression of each isoform was also seen in organ of Corti (OC), spiral
      ganglion (SG), cochlear nerve (CN) and Kolliker's Organ (KO). These observations
      suggest that individual isoforms may exert specific actions postnatally during
      final cochlear maturation.

PMID- 7572126
TI  - Evidence of cellular supplies to the endolymphatic sac from the systemic
      circulation.
AB  - Donor T lymphocytes injected into the host systemic circulation were observed to
      infiltrate into the host endolymphatic sac in mice. These findings suggest that
      the endolymphatic sac, a major immune organ in the inner ear, is supplied with
      immunocompetent cells from the systemic circulation. This concept is consistent
      with clinical reports that inner ear disorders accompany certain systemic
      autoimmune diseases. Bone marrow transplantation to replace autoreactive
      immunocompetent cells with normal cells should be considered as a potential
      therapy for inner ear autoimmune diseases and an alternative to conventional
      treatments.

PMID- 7572125
TI  - Effects of experimental round window membrane laceration on the free amino acid
      profile of perilymph.
AB  - To evaluate biochemical changes of inner ear fluid following perilymphatic
      fistula (PLF), free amino acid (FAA) profiles of perilymph in experimental PLF
      were determined using high performance liquid chromatography (HPLC). Thirty-five
      guinea pigs were anesthetized and prepared as PLF models by perforating the round
      window membrane (RWM) of the left ear. Right ears served as controls. Samples (2
      microliters) were aspirated from scala tympani through a RWM perforation. Animals
      were divided into two groups according to time of sampling following PLF
      induction: 2-week group (n = 17) and 4-week group (n = 18). Compound action
      potential (CAP) evoked by 1, 2, 4 and 8 kHz tone bursts were measured using a
      round window electrode from the left ear before PLF induction and from both ears
      before final sampling. RWM perforations were completely closed at the time of the
      final sampling in 8 of 17 animals from the 2-week group, and 15 of 18 animals
      from the 4-week group. In comparison with that in control ears, concentrations of
      FAA throughout all profiles was dramatically elevated in the PLF ears with a
      healed RWM perforation. Most PLF ears with persistent RWM perforation showed
      minimal differences between 2-week and 4-week groups. No remarkable CAP threshold
      changes were found at any frequencies tested following PLF induction in both the
      2-week and 4-week groups. The unchanged 8 kHz threshold suggests that FAA
      concentration increases only at the basal end of the cochlea. FAAs accumulate
      within the basal end of scala tympani in ears with a healed RWM.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572127
TI  - MR imaging of neuronal transport in the guinea pig facial nerve: initial
      findings.
AB  - Certain dextran coated iron oxides such as MION (monocrystalline iron oxide
      nanocompound) coupled to wheat germ agglutinin (MION-WGA) have been shown to
      exhibit i) neuronal uptake ii) axonal transport and iii) strong magnetic effects
      on tissues (superparamagnetism) in which they are localized. In the current
      study, we utilized such an agent to visualize axonal transport in the facial
      nerve in vivo by magnetic resonance (MR) imaging. Following injection of the
      compound into the facial nerves of guinea pigs, MR images were obtained at
      multiple time points (1, 3 and 5 days) and the imaged tissues were processed for
      subsequent histological examination. In nerves that had been injected with MION
      WGA, the entire nerve appeared as a uniformly hypointense structure with a
      calculated transport rate of 5 mm/day. By 3 days, the agent within the facial
      nerve was traceable by MRI from a site of injection in the buccal branch to the
      stylomastoid foramen. Fluorescence and autoradiography studies confirmed axonal
      transport. These results show that MION-based magnetopharmaceuticals can be used
      to demonstrate slow axonal transport, and thereby visualize functional peripheral
      nerves in vivo by MR imaging. The method holds promise for developmental
      neuroscience research as well as a method to detect neural abnormalities by MR
      imaging.

PMID- 7572129
TI  - Biomechanical characteristics of the middle ear system measured by a new method.
      III: Comparisons with tympanometric measurements.
AB  - A new method for studying middle ear mechanics is reported in which we measured
      ear canal pressure changes due to tympanic membrane volume displacements. One
      feature of this pressure-volume relationship (PVR) is the determination of
      dynamic compliance of the middle ear system (MES). We found a significant
      correlation between dynamic compliance expressed by the PVR and static acoustic
      compliance by tympanometry. Another feature of the PVR was determination of the
      mechanical zero position of the tympanic membrane (TM) defined in terms of
      minimum hysteresis, which correlated significantly with the neutral position of
      the TM determined by tympanometry, but indicates a retracted position of the TM
      relative to tympanometry. Finally the hysteresis effect of the MES measured with
      the PVR was compared and found to fall within the range of peak difference found
      in bidirectional tympanometric recordings, which is also influenced by phase
      delay and semi-dynamic conditions.

PMID- 7572128
TI  - Laminin promotes differentiation, adhesion and proliferation of cell cultures
      derived from human acoustic nerve schwannoma.
AB  - The influence of laminin on cell cultures derived from unilateral acoustic nerve
      schwannomas was investigated. Cell cultures were initiated from 12 schwannomas,
      removed via the enlarged middle cranial fossa approach. Tumor tissue was
      dispersed by collagenase treatment and cells seeded in uncoated or laminin-coated
      culture dishes. Confluent cultures were immunocytochemically characterized with
      antibodies against S-100, CD 68, factor VIII-related antigen and type IV
      collagen. Cell adhesion in response to different doses of laminin was evaluated
      with an electronic cell counter. The effect of laminin on cell proliferation was
      assessed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into
      cellular DNA. Cells cultured on laminin as substrate appeared more differentiated
      with long, fusiform, cytoplasmic processes. Cultured cells stained positive for S
      100, not for factor VIII-related antigen or CD 68. Only cells cultured on laminin
      deposited a dense extracellular network of type IV collagen. When laminin was
      added to the culture medium, cell attachment and proliferation was stimulated in
      a dose dependent manner. Maximal stimulation of both was observed with a laminin
      concentration of 50 micrograms/ml, which induced a nearly 2-fold increase in cell
      attachment and an approximately 66% increase in DNA content. Since laminin is a
      major component of the extracellular matrix in schwannomas, the possibility
      exists that laminin is also mitogenic for human neoplastic Schwann cells in situ.

PMID- 7572130
TI  - The influence of an insecticide on the function of the eustachian tube.
AB  - Organophosphorus compounds in the form of insecticides are in widespread use and
      have recently attracted considerable interest as environmentally toxic agents. As
      little is known about the effect of environmental toxins on the tubal function in
      the ear, we studied the middle ear pressure necessary to force the eustachian
      tube to open (POL = pressure opening level) under physiological conditions in
      laboratory mini pigs and under the influence of an i.v. organophosphorus compound
      (Paraoxon). The median POL in the untreated animals was 6.4 kPa (n = 8). After
      intoxication with Paraoxon the median POL increased to 12.0 kPa (n = 8). Tubal
      instillation of surfactant in intoxicated pigs reduced the POL to a median of 7.3
      kPa (n = 8), while in non-intoxicated animals (n = 4) it also lowered the POL,
      though not significantly. These results suggest that organophosphorus compound
      interferes with the surfactant-dependent tubal patency.

PMID- 7572131
TI  - Effect of oxatomide on otitis media with effusion--an experimental study.
AB  - The therapeutic effect of oxatomide on experimental otitis media with effusion
      (OME) induced by secondary immune response was investigated in chinchillas.
      Oxatomide was administered daily in three different doses (5, 10, 30 mg/kg
      b.w.t.) for a period of 2 weeks, starting 2 days after the instillation of
      keyhole limpet hemocyanin (KLH) into the tympanic cavity. The severity of OME was
      assessed by observing the eardrum under a surgical microscope, by tympanography,
      and by histological findings. The concentrations of leukotriene C4 and LTD4 in
      middle ear effusion (MEE) were also measured, 7 days after the KLH instillation.
      It was found that oral administration of oxatomide in dosages of 10 and 30 mg/kg
      alleviated the experimental OME. The mean LTD4 concentration measured in MEE from
      chinchillas given 30 mg oxatomide was significantly lower than that measured in
      the control group. The radioactivity of 14C-labelled oxatomide in MEE and the
      autoradiographic findings revealed that orally administered oxatomide was rapidly
      absorbed from the digestive tract and transported to the middle ear via blood
      circulation. The findings suggest that the effect of oxatomide can be anticipated
      in patients with OME.

PMID- 7572132
TI  - Bulbar morphology and expression of bulbar dopamine and parvalbumin in
      experimentally-induced anosmic rats.
AB  - Morphological study was carried out in rats with olfactory dysfunction induced by
      deafferentation of serotonergic fibers in the olfactory bulb. With a computer
      capable of area measurements, olfactory bulbs of the anosmic rats were found to
      be decreased in size to 61% of control bulbs, and all bulbar layers were involved
      in the bulbar shrinkage. Given areas of each bulbar layer in control bulbs to be
      100%, percentages of each bulbar layer in the anosmic rats were 23% in the
      olfactory nerve layer, 54% in the glomerular layer, 63% in the external plexiform
      layer, 83% in the internal plexiform layer and 81% in the granule cell layer.
      Dopamine-and parvalbumin-containing neurons were examined immunohistochemically
      in the experimentally-induced anosmic rats. As a result, immunoreactive neurons
      for these two chemical substances were significantly decreased in number
      (dopamine, 33% of control value; parvalbumin, 46% of control value). The present
      study, using an animal model of anosmia, provided quantitative data on the bulbar
      atrophy and showed effects of anosmia on expression of dopamine and parvalbumin
      in the bulb.

PMID- 7572133
TI  - Histologic structure of antrochoanal polyps.
AB  - The antrochonanal polyp (ACP) is defined as a maxillary sinus polyp that
      originates in the maxillary sinus, passes through the sinus ostia, and extends
      into the choana. The aim of this study was to compare the histologic findings of
      40 cases of ACP with those of allergic and non-allergic nasal polyps, and so
      possibly to elucidate the pathogenesis of ACP. No allergy could be verified in
      any of the ACP patients. Inflammatory cell infiltration was significantly more
      severe in the ACP group than in the allergic polyp group. Eosinophilic
      infiltration was significantly less severe in the ACP group than in the allergic
      polyp group. Edema was not significantly different between the ACP, allergic, and
      non-allergic groups. In the ACP group, the presence of submucous glands was
      significantly less pronounced than in the ordinary nasal polyp groups. The
      fibrous type was present significantly more often than the infiltrative or
      granulating type in the ACP group. The histologic findings and clinical features
      of the ACP indicate that it has little causal relationship with nasal allergy but
      is all the more intimately associated with inflammatory processes. The paucity of
      submucous glands suggests that the ACP results from edematous hypertrophy of the
      respiratory epithelium rather than from distension of the glandular structures.

PMID- 7572134
TI  - Application of polylactic acid polymer in the treatment of acute maxillary
      sinusitis in rabbits.
AB  - To evaluate the therapeutic effects of topical antibiotic delivered by polylactic
      acid (PLA) polymer on paranasal sinusitis, we induced maxillary sinusitis in 32
      New Zealand white rabbits by obstructing the maxillary sinus ostium and
      inoculating the sinus cavity with Streptococcus pneumoniae. The rabbits were
      divided into three groups: a control group (group 1) treated only by reopening
      the ostium, a group (group 2) treated by both reopening the ostium and injecting
      ampicillin (40 mg/kg/day), and a group (group 3) in which ampicillin in the PLA
      carrier (0.326 mg) was placed within the sinus after ostial patency was
      reestablished. The number of colony forming units (CFU) was lowest in group 3,
      followed by groups 2 and 1. Ampicillin concentration in the maxillary sinus
      secretion of group 3 was significantly higher than in group 2. The results
      suggest that treatment with PLA-ampicillin polymer may maintain high therapeutic
      concentrations of ampicillin in maxillary sinus secretion.

PMID- 7572135
TI  - Vocal function in patients with unilateral vocal fold paralysis before and after
      silicone injection.
AB  - A total of 240 patients with unilateral vocal fold paralysis (UVFP) underwent
      transcutaneous intrafold silicone injection (TCIFSI) for the purpose of vocal
      rehabilitation during the period from 1983 to 1993 in the Kurume University
      Hospital. Their vocal function was evaluated and the effects of TCIFSI upon the
      vocal function were investigated. The patients with UVFP presented with an
      increase in airflow during phonation; a decrease in maximum phonation time and
      fundamental frequency (F0) range and sound pressure level (SPL) range of
      phonation; and an increase in pitch perturbation quotient, amplitude perturbation
      quotient and normalized noise energy in the voice signal. TCIFSI resulted in a
      decrease in airflow, an increase in phonation time and F0 and SPL range of
      phonation, and a decrease in pitch and amplitude perturbation and noise in the
      voice signal. Patient's own subjective evaluation presented with an improvement
      of his/her voice after TCIFSI.

PMID- 7572136
TI  - Voice evaluation before and after laser excision vs. radiotherapy of T1A glottic
      carcinoma.
AB  - Quality of voice after treatment for T1A glottic squamous cell carcinoma was
      studied in two matched groups of males treated either with CO2 laser cordectomi
      (n = 18, mean age 65.2 years) or with full dose radiotherapy (n = 18, mean age
      65.1 years). All patients had histologically verified invasive squamous cell
      carcinoma. Fifteen male patients (mean age 63.9 years) without laryngeal
      disorders were used as controls. Voice recordings prior to treatment, and both at
      3 months and at 2 years after completed treatment were analyzed. Acoustic
      measures of shimmer, jitter, breathiness, harmonic-to-noise ratio and fundamental
      frequency (F0) average were calculated with the Soundscope program. Two plain
      measures were also used: time required to read a running speech voice sample, and
      number of breaths. Perceptual voice analysis was performed blindly by two groups
      of listeners, Group A (4 experienced listeners) and Group B (4 naive listeners).
      Group A estimated quality of voice according to a modified GRBAS score, whereas
      Group B estimated Grade only. We found voice quality both at 3 months and at 2
      years after radiotherapy to be significantly better than after laser treatment,
      as assessed by the acoustic variables breathiness, jitter, F0 average, running
      speech voice sample reading time and number of breaths. The perceptual variables
      Grade (Group A and B), Breathiness, Asthenia and Strain were also significantly
      better after radiotherapy.

PMID- 7572137
TI  - Effect of blood transfusion on tumor recurrence and postoperative
      pharyngocutaneous fistula formation in patients subjected to total laryngectomy.
AB  - Some surgical oncologists and otolaryngologists have reported that transfusion
      induced immunosuppression may increase the incidence of recurrence and infectious
      complications in patients subjected to head and neck surgery for carcinoma. The
      relationship between intra-operative blood transfusion and postoperative
      pharyngocutaneous fistula formation and/or tumor recurrence is controversial. In
      a retrospective study of 110 total laryngectomized patients, we found no
      statistically significant differences between the transfused and nontransfused
      groups in terms of tumor recurrence and fistula formation.

PMID- 7572139
TI  - Neurosensory hearing loss in neonates with severe hypoxemia.

PMID- 7572138
TI  - Collagen IV and tenascin immunoreactivity as prognostic determinant in benign and
      malignant salivary gland tumours.
AB  - The expression of collagen IV and tenascin was studied in a series of 219
      salivary gland tumours with special emphasis on the prognostic significance of
      these extracellular matrix constituents. Continuous and uninterrupted staining of
      the basal membrane with collagen IV antibody was found in 62% (64/103) of the
      carcinomas and in 92% (107/116) of the benign tumours, the staining being weak
      and interrupted in 38% (39/103) and 8% (9/116) of cases, respectively. Weak
      immunoreactivity for collagen IV was significantly (p = 0.05) associated with
      recurrences of the malignant salivary gland tumours. Intense collagen IV staining
      of the basal membrane was more frequent (35.9%) in patients who were alive, as
      compared with that (19.4%) of the patients who died of salivary gland cancer (p =
      0.03). Similarly, the intactness of the basal membrane was directly related to
      patient survival. In benign tumours, no such differences were found. In
      multivariate analysis, collagen IV immunoreactivity was related to the age of the
      patients (p = 0.007) and to tumour diameter > 4.0 cm (p = 0.005). Intense
      tenascin immunoreactivity was found in 45% (46/103) of the carcinomas and in 43%
      (50/116) of the benign tumours, 55% (57/103) and 57% (66/116) of the cases being
      entirely tenascin-negative, respectively. Tenascin immunoreactivity was not
      related to the clinical behaviour of malignant salivary gland tumours. In benign
      tumours, an intense staining for tenascin was a determinant of recurrent disease
      (p = 0.05). In multivariate analysis, tenascin immunoreactivity was intimately
      associated with erbB-2 positivity (p = 0.03) and weak staining of collagen IV (p
      = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572140
TI  - Inhaled nitric oxide therapy for persistent pulmonary hypertension of the
      newborn.
AB  - Increasing evidence suggests that the pulmonary vascular endothelium is an
      important mediator of resting pulmonary vascular tone through the synthesis and
      release of a variety of vasoactive substances including nitric oxide (NO). In
      addition, pulmonary endothelial dysfunction (such as impairment of NO synthesis)
      is present in lung injury and may contribute to the pathophysiology of pulmonary
      hypertensive disorders. Recently, exogenously administered NO gas has been
      utilized to treat infants with persistent pulmonary hypertension of the newborn
      (PPHN). These preliminary studies suggest that inhaled NO is a promising new
      therapy for the treatment of infants with PPHN. Controlled clinical trials must
      now be performed to determine if the use of inhaled NO improves the long-term
      outcome of patients with PPHN. Long-term exposure must be monitored closely for
      potential toxicity which includes methemoglobinemia and lung injury secondary to
      peroxynitrite and nitrogen dioxide production.

PMID- 7572141
TI  - Fetal arrhythmias: intrauterine diagnosis, treatment and prognosis.
AB  - Fetal echocardiography can provide useful information for the evaluation of fetal
      arrhythmias. Between 1980 and 1993, 44 fetuses with arrhythmias were diagnosed in
      utero at 12 and 40 weeks of gestation in Kurume University Hospital. Fetal
      bradycardia, tachycardia and ectopic beats were revealed in 17, seven and 20
      fetuses, respectively, and their clinical features and prognosis were evaluated.
      In the 17 fetuses with bradycardia, eight were associated with congenital heart
      defect, and six of these developed to fetal hydrops. Of the 17 fetuses, four died
      in utero, one was terminated, and six died after birth. The other six cases
      survived. Three of these had a pacemaker implanted after birth. In the seven
      fetuses with tachycardia, transplacental anti-arrhythmic drugs were administered
      in five cases and conversion of the arrhythmia was achieved in four. None of the
      cases was associated with any congenital heart defect, and none died. Three
      infants had paroxysmal tachycardia postnatally. In the 20 fetuses with ectopic
      beats, arrhythmia was observed postnatally in 10, but all of these were resolved
      within 3 months after birth. Fetal bradycardias carried a poor prognosis in most
      cases and further studies are required to establish effective treatment. Some
      cases of fetal tachycardia developed recurrent tachycardia postnatally. Close
      follow-up of the newborn is therefore necessary.

PMID- 7572142
TI  - Clinical study of heavy-for-dates neonates.
AB  - Incidence and morbidity rates of heavy-for-dates (HFD) term neonates were
      examined to elucidate whether HFD neonates are at high risk. At the same time the
      criteria for HFD, defined by the fetal growth curve published in 1983 by the
      Ministry of Health and Welfare, were evaluated. A sample of 15,377 term neonates
      who were born between 1984 and 1990 were obtained. Still-births and neonates from
      non-Japanese mothers were excluded. The overall incidence of HFD neonates was
      5.13%. The morbidity rate excluding idiopathic hyperbilirubinemia was 10.0%,
      which increased with gestational age and was accompanied by an increment of birth
      trauma. The main diagnosis of hospitalization of HFD neonates was birth trauma
      followed by respiratory disorders. The incidences of hypoglycemia and
      polycythemia, regarded as major problems of HFD neonates, were low. The main
      causes of hospitalization of HFD neonates are associated with difficulty at
      delivery due to their heavy weight. There were no significant differences in the
      morbidity rate of neonates defined by the deviation of birth-weight from the mean
      +1.3 s.d. to +2.5 s.d. On the other hand, neonates of birth weight over 3750 g
      had significantly high morbidity rates. Criteria defined by the absolute birth
      weight of over 3750 g are more appropriate to screen risk neonates with heavy
      weight rather than the criteria for HFD as being above mean birth-weight +1.5
      s.d.

PMID- 7572143
TI  - Acquired cytomegalovirus infection and blood transfusion in preterm infants.
AB  - The urinary excretion of cytomegalovirus (CMV) DNA, amplified by polymerase chain
      reaction using two pairs of primers for late antigen (LA) and major immediate
      early antigen (MIE), and serum CMV IgM were examined in 85 pre-term infants
      (birth-weight less than 2000 g) on admission and monthly until 6 months after
      birth. Of these 85 infants, 27 had blood exchange transfusions (BET) and 28 had
      bolus blood transfusions two to nine times. Fifteen of 27 infants underwent BET
      with blood that had been filtered through Pall RC100 leukocyte removal filter;
      the other 12 with unfiltered blood. Neither urinary CMV DNA nor serum CMV
      specific IgM was detected at birth in any of the 85 pre-term infants; during the
      first 6 months after birth urinary CMV DNA, for both MIE and LA, appeared in 22
      of the 85 infants (25.9%) and CMV IgM was positive in 14 of the 85 (16.5%). Nine
      of the 12 (75%) infants who received BET of unfiltered blood showed a
      significantly higher prevalence of urinary CMV DNA compared to the infants in the
      other three groups (i.e., those who received no blood transfusion, those who had
      bolus blood transfusions, or those who received BET of filtered blood; P < 0.01
      in each instance). In a logistic regression model, CMV DNA urinary excretion was
      significantly associated with the mode of blood transfusion (unfiltered BET), and
      the Odds ratio was 38.9 (95% confidence interval, 9.4-160). There was no
      significant association with other independent variables such as gender, mother's
      seropositivity, gestational age, birth-weight or delivery mode.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572144
TI  - Dependence of canine right coronary arterial flow upon heart rate and right
      ventricular pressure.
AB  - There is a paucity of knowledge regarding right coronary pulsatile hemodynamics
      when the right ventricle is under hemodynamic overload as is often the case in
      pediatric patients with congenital cardiac anomalies. To elucidate the exact
      mechanisms for the right coronary artery (RCA) to cope with the overload, we
      studied nine open-chest adult Beagles and analyzed the flow signals of the RCA in
      relation to independently varied heart rate (pacing) and right ventricular
      pressure (pulmonary artery banding). Both increased heart rate and right
      ventricular pressure increased the total volume flow of the RCA. The diastolic
      over total flow ratio (D/T), however, enlarged on increasing right ventricular
      pressures while it declined on increasing heart rates. Our data confirmed, as
      well, that increased flow of RCA on rising heart rate was provided mainly by an
      increase in systolic phase, while the increase on augmented right ventricular
      pressure was provided by the increase in diastolic phase. The RCA manages to
      deliver blood to the right ventricular musculature in two different ways in
      response to increasing heart rate and right ventricular pressure.

PMID- 7572145
TI  - Long-term prognosis and prognostic factors of Japanese children with mesangial
      proliferative glomerulonephritis without IgA deposition.
AB  - Mesangial proliferative glomerulonephritis without IgA deposition (non-IgA
      MesPGN) is commonly detected in biopsy specimens, but the clinicopathological
      correlation with the long-term prognosis still remains obscure. The aim of our
      study is to elucidate the long-term prognosis and the clinicopathological
      prognostic factors in patients with non-IgA MesPGN. We mailed questionnaires to
      122 patients with primary glomerulonephritis who were biopsied between 1963 and
      1975. Information was obtained from 109 of these 122 patients and 55 were
      histologically rediagnosed as having non-IgA MesPGN. The histological alterations
      of glomeruli and tubulointerstitium were classified into five grades. The mean
      period between the biopsy and the questionnaires was 20.5 years. Six of the 55
      patients with non-IgA MesPGN developed end-stage renal failure and
      histopathological alterations of renal biopsies from these six patients were
      classified into grade IV or V. The presence of hypertension, heavy proteinuria of
      over 2+ or renal insufficiency at the biopsy was related to the severe
      histological changes, a grade of IV or V and to a poor prognosis. The renal
      survival rate of all the 55 patients was 88.3% at 20 years after the biopsy,
      while that of the 12 patients with severe histological changes was 48.6%.
      Although non-IgA MesPGN is considered to be a heterogeneous disease, we cannot
      ignore the incidence of this disease and thus consider it to be one of the
      important primary glomerulonephritides that occur in childhood.

PMID- 7572146
TI  - Different kinetics of antibody responses between IgA and IgG classes in
      nasopharyngeal secretion in infants and children during primary respiratory
      syncytial virus infection.
AB  - The secretory antibody responses in 34 infants and children (20 days-17 months
      old) with lower respiratory tract disease following primary respiratory syncytial
      virus (RSV) infection were determined using a sensitive tissue culture enzyme
      linked immunosorbent assay. None of the patients in the acute phase showed IgA
      antibody responses. In contrast significant IgG antibody responses which were
      thought to be maternally derived were observed in infants younger than 2 months
      of age. In the convalescent phase sample, significantly high IgA antibody
      responses were observed in all patients except one, and there was no significant
      difference in magnitude of antibody activity between patients younger than 8
      months and patients older than 8 months. However, IgG antibody responses in
      infants younger than 8 months were significantly lower than in subjects 8 to 17
      months old. Notably, infants younger than 2 months developed no significant IgG
      antibody activity in the convalescent phase. These observations suggest that the
      antibody activity which contributes to recovery from primary infection by RSV in
      younger infants may be IgA rather than IgG class antibodies. These observations
      also suggest that the presumptive immunosuppression mediated by maternally
      derived antibodies may predominantly influence the IgG antibody response rather
      than the development of local IgA antibody activity.

PMID- 7572148
TI  - Interleukin-2 receptor positive T and B cells in children with acute severe
      asthmatic attack.
AB  - Subpopulations of interleukin-2 receptor (IL-2R)-positive CD4 and CD8 T cells and
      IL-2R+CD20 B cells in the peripheral blood lymphocytes as well as serum
      concentrations of soluble IL-2R (sIL2R) were measured in children aged 1-7 years
      who suffered acute severe asthmatic attack. Subpopulations of CD4+IL-2R+ cells,
      CD8+IL-2R+ cells and CD20+IL-2R+ cells in the peripheral blood lymphocytes at
      acute severe asthmatic attack phase were significantly higher than those at non
      asthmatic attack phase (P < 0.02, P < 0.03 and P < 0.02, respectively).
      Subpopulations of CD20+IL-2R+ cells in the peripheral blood lymphocytes
      significantly decreased 5-10 days after acute severe asthmatic attack (at
      recovery phase, P < 0.02) and were significantly correlated with clinical
      severity of asthmatic attack (P < 0.05). These results indicated that activation
      of both T cells and B cells was important in the pathogenesis of acute asthmatic
      attack in young children.

PMID- 7572147
TI  - Indirect hemagglutination assay for antibodies to Escherichia coli
      lipopolysaccharides O157, O111 and O26 in patients with hemolytic uremic
      syndrome.
AB  - We examined sera from 10 patients with hemolytic uremic syndrome (HUS) and 51
      controls, with and without diarrhea, for antibodies to Escherichia coli
      lipopolysaccharides (LPS) O157, O111 and O26 using the indirect hemagglutination
      (IHA) assay. A significant rise (to a titer of > or = 2560) in IHA antibody to
      O157 LPS was detected in eight of the 10 HUS patients, to O111 in two patients,
      one of whom showed concomitantly an antibody rise to O157, but to O26 in no
      patients. The IHA titers fell rapidly after the acute phase of the illness. Of
      the control sera 15 (29.4%) non-specifically agglutinated uncoated sheep red
      blood cells (SRBC) at a titer of > or = 80, six (3.9%) at > or = 320 and the
      maximum was 640. In spite of the relatively low level of non-specific
      agglutination the IHA appeared to be a useful screening method to identify
      verotoxin-producing E. coli infections at the early stage of HUS because the
      titers were clearly higher than non-specific agglutination and the assay is easy
      to perform and gives results quickly. Artificial carriers are being considered
      for use in place of SRBC to diminish the non-specific hemagglutination.

PMID- 7572149
TI  - Trends in survival of childhood malignancy for the past three decades. I:
      Leukemia, malignant lymphoma, neuroblastoma, retinoblastoma and neoplasms of the
      urinary and digestive organs. The Committee for the Studies of the Treatments and
      the Biological Characteristics of Childhood Cancers.
AB  - Survival of some types of childhood neoplasms has improved considerably but
      remained poor for other types. Improvement in survival rate of common types of
      childhood neoplasms over the past three decades was assessed at the largest
      children's hospital in Japan. Using the data of the cancer registry of the
      hospital which recorded all the patients from 1965 to 1993, totalling 1026 cases,
      survival rate was analyzed for each type of neoplasm categorized by the S
      classification for childhood neoplasms, a modification of the International
      Classification of Diseases. Survival was assessed for five 5 year periods from
      1965 and a 4 year period from 1990-93. The 5 year survival rate for all neoplasms
      combined improved from 21.8% in the 1965-69 period to 73.3% in the 1985-89
      period. Female patients' survival was better than male patients' in all periods.
      The improvement in survival rate was considerable for leukemia and malignant
      lymphoma, fairly good for neoplasms of the renal (mostly Wilms' tumor) and
      digestive (mostly hepatoblastoma) organs and moderate for neuroblastoma. Overall,
      survival rates of childhood neoplasms improved considerably. Much of this
      improvement was explained by a great improvement in survival rates of neoplasms
      of the blood which constituted the majority of patients.

PMID- 7572150
TI  - Trends in survival of childhood malignancy for the past three decades. II:
      Neoplasms of the respiratory, skeletal, genital, skin and endocrine organs and
      malignant teratomas. The Committee for the Studies of the Treatments and the
      Biological Characteristics of Childhood Cancers.
AB  - Survival of childhood neoplasms has improved considerably during the past three
      decades. Improvement in survival rate for relatively infrequent neoplasms was
      assessed based on data obtained from the largest children's hospital in Japan.
      Using the data of the cancer registry of the hospital which recorded all the
      patients from 1965 to 1993 totalling 1026 cases, survival rate was analyzed for
      each type of neoplasm categorized by the S-classification for Childhood
      Neoplasms, a modification of the International Classification of Diseases.
      Survival was assessed for three 10 year periods from 1965 for infrequent
      neoplasms and for two 15 year periods for rare neoplasms. Improvement of survival
      was considerable in the neoplasms of the respiratory organs, genital organs and
      germ cell tumors, moderate in bone tumors and poor in the muscle and connective
      tissues. In conclusion, in some types of relatively infrequent neoplasms,
      survival improved considerably. But in soft parts and connective tissues (mostly
      rhabdomyosarcoma) improvement of survival was poor.

PMID- 7572152
TI  - Lymphocyte subpopulations in children with vitamin D deficient rickets.
AB  - Recent studies have shown 1,25(OH)2D3-mediated modulation of the immune system.
      We examined lymphocyte subpopulations of 16 children with nutritional rickets.
      Most of the patients suffered more frequent infection episodes than the control
      group of 15 healthy children and low serum levels of 25OHD and 1,25(OH)2D, such
      as 38.2 +/- 8.6 ng/mL and 15.7 +/- 2.6 pg/mL respectively. This decrease
      correlated with a significant decrease in total T lymphocytes and an increase in
      B lymphocytes expressing surface IgA, IgM, IgG molecules. These results suggest
      that vitamin D plays an important role in the impaired functions of T lymphocytes
      which may lead to frequent infection episodes in nutritional rickets.

PMID- 7572151
TI  - Comprehensive treatment of advanced neuroblastoma involving autologous bone
      marrow transplant.
AB  - Encouraging results are reported with high-dose chemotherapy and total body
      irradiation followed by autologous bone marrow transplantation in the treatment
      of advanced neuroblastoma. However, relapse remains a significant problem. We
      used high-dose chemotherapy, surgery, intraoperative radiation and an autologous
      bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis
      retinoic acid to treat 36 children with advanced neuroblastoma. This
      comprehensive treatment appears to improve the survival rate of patients with
      advanced neuroblastoma, including those with N-myc amplification and bony
      involvement. The disease-free survival rate was 66% (95% confidence interval, 49
      84%) at 3 years. All patients who received 13-cis-retinoic acid developed
      cheilitis, but no bone marrow depression occurred in these patients. Five
      patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have
      been related to the procedure used for total body irradiation. Patients who had
      their kidneys shielded during this procedure did not develop this syndrome.
      Patients who received local irradiation at the primary site showed no evidence of
      relapse in this region, indicating that such therapy may help to prevent a
      relapse. These data suggest a high rate of 3 year disease-free survival with this
      treatment strategy. The nonrandomized nature of the study and use of multiple
      modalities precludes analysis of the specific contribution of each.

PMID- 7572153
TI  - Increased incidence of spina bifida occulta in fluorosis prone areas.
AB  - Spina bifida, a congenital deformity of the posterior wall of vertebrae of the
      spine, is a midline defect of skin, vertebral arches and neural tube, usually in
      the lumbosacral region. Its incidence is reported to be 0.2 to 0.4 per 1000 live
      births. Various hypotheses have been put forward as etiological factors for spina
      bifida including consumption of potato affected by blight and hardness of
      drinking water but these have not been proven. Two groups of 50 randomly chosen
      children were established. The study group consisted of children aged 5 to 12
      years, weighing 15 to 30 kg, consuming fluoride rich drinking water (4.5 and 8.5
      ppm fluoride; WHO permissible limit is 1.5 ppm fluoride), and manifesting either
      clinical, dental and/or skeletal fluorosis. The control group consisted of age
      and weight-matched children, consuming less than or equal to 1.5 ppm fluoride in
      drinking water and not showing any evidence of fluoride toxicity. These children
      were evaluated for antenatal history, general clinical examination (especially
      for dimples, tufts of hair, haemangioma on skin throughout the length of spine),
      other congenital abnormalities, evidence of fluoride toxicity, biochemical
      estimation for fluoride levels in blood and serum and by skiagrams of the spine
      to examine for the presence of spina bifida occulta. A total of 22 (44%) of the
      50 children in group A, the study group, and 6 (12%) of the 50 children in group
      B, the control group, revealed spina bifida occulta in the lumbosacral
      region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572154
TI  - Electron microscopic finding of eccrine sweat gland epithelial cells in a patient
      with Krabbe disease.
AB  - A 13 month old boy was found to have severely reduced beta-galactocerebrosidase
      activity suggesting infantile Krabbe disease. Clinically, the patient showed a
      progressive neurological deterioration with white-matter disease on radiological
      study. Axillary skin biopsy was performed to support the diagnosis. On electron
      microscopy, needle-like inclusions, which are the typical finding seen in the
      cytoplasm of astrocytes and Schwann cells in the classic infantile form, were
      present in eccrine sweat gland epithelial cells. This method is useful for
      diagnosis when nerve biopsy and biochemical analysis are not readily available.

PMID- 7572156
TI  - The first report of a patient with interrupted inferior vena cava, multiple post
      renal veins and azygos-hemiazygos continuation.
AB  - The first case of a patient with interrupted inferior vena cava, four post-renal
      veins and an azygoshemiazygos continuation is presented. The complicated
      anomalies were omphalocele and atrial septal defect. Cine-magnetic resonance
      imaging and cardiac catheterization showed an anomalous retroaortic left
      innominate vein, azygos-hemiazygos continuation in the prerenal portion, arch
      formed renal vein in the renal portion and four embryonic vessels in the post
      renal portion. Combination of these anomalies in the major venous system
      suggested that the inferior vena cava had failed to form and that the bilateral
      embryonic venous system, postcardinal and supracardinal veins, persisted to be
      the systemic venous channels.

PMID- 7572155
TI  - Type La glycogen storage disease with focal nodular hyperplasia in siblings.
AB  - Glycogen storage disease type I (GSD-I) is an inherited disorder that is due to a
      glucose-6-phosphatase (G6Pase) deficiency. There have been recent reports of
      hepatocellular tumors in adults with this disease. Hepatic adenoma is the most
      common tumor described but others, including hepatocellular carcinomas,
      hepatoblastomas, and focal nodular hyperplasia (FNH) have been reported. FNH of
      the liver is a rare benign lesion that has been reported in eight patients with
      GSD-I. Three of these eight patients, in addition to the patient in our study,
      had been treated with portacaval shunts. When these patients were compared with
      patients who had not received such treatment, it appeared that the portacaval
      shunts may have induced the development of FNH and may have been associated with
      earlier complications. FNH is a benign tumor that may coexist with adjacent
      fibrolamillar carcinomas and/or adenomas and requires careful follow-up.

PMID- 7572157
TI  - Advanced atrioventricular block associated with atrial tachycardia caused by
      Mycoplasma pneumoniae infection.
AB  - Atrial tachycardia with atrioventricular (AV) block has been recognized as a
      common manifestation of digitalis toxicity. We describe here an unusual case of
      transient advanced AV block associated with atrial tachycardia in a 6 year old
      boy with evidence of Mycoplasma pneumoniae infection.

PMID- 7572159
TI  - Selective IgA deficiency with unusual features: development of common variable
      immunodeficiency, Sjogren's syndrome, autoimmune hemolytic anemia and immune
      thrombocytopenic purpura.
AB  - We report on a girl with selective IgA deficiency and persistently low complement
      component 4 (C4) levels compatible with heterozygous C4 deficiency. Deterioration
      of her serum immunoglobulin levels and transition to common variable
      immunodeficiency were observed within a 5 year follow-up. She also developed
      Sjogren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic
      purpura. While these abnormalities have been described before in various
      combinations, to our knowledge, they have not been reported in a single
      individual.

PMID- 7572158
TI  - Transient dilatation of the abdominal aorta in an infant with Kawasaki disease
      associated with thrombocytopenia.
AB  - We report on an 8 month old infant with Kawasaki disease associated with giant
      coronary aneurysms and transient thrombocytopenia. The patient's platelet count
      decreased to 24,000/mm3 on the 31st day of illness and fibrin degradation product
      was 5 micrograms/mL. Platelet count increased to the normal level (357,000/mm3)
      on the 35th day of illness. On the 27th day of illness, dilatation of the distal
      abdominal aorta adjacent to the bifurcation of the iliac arteries was observed by
      B-mode and color Doppler ultrasonography. It gradually returned to a normal size
      by the 45th day of illness. Aspirin administered from the 3rd to the 26th day of
      illness was replaced with flubioprophen because of liver dysfunction. Although we
      can not eliminate aspirin allergy as the cause of the transient thrombocytopenia,
      we think that the thrombocytopenia may have been related to the regression of the
      abdominal aorta.

PMID- 7572160
TI  - Relation between serum hepatitis C virus-RNA levels and efficacy of interferon
      beta therapy.
AB  - We performed two courses of interferon-beta (IFN-beta) to a child with chronic
      hepatitis C. A complete response was not obtained by the first interferon
      treatment, however, the results of the second treatment differed from those of
      the first. Hepatitis C virus (HCV)-RNA remained negative and both aspartate
      aminotransferase and alanine aminotransferase levels remained normal after
      completion of the second course. From these results we estimated that HCV-RNA
      levels before IFN therapy could be significantly associated with the efficacy of
      this treatment. The serum level of HCV-RNA was 10(6) copies/50 microL before the
      first treatment, but was 10(3) copies/50 microL before the second course. We
      conclude that IFN therapy to children with hepatitis C should always be directed
      at providing a cure. Even if the clinical effects of the first course are minimal
      decreasing quantities of HCV-RNA still offer hope for cure by subsequent
      readministration.

PMID- 7572161
TI  - Hypothyroidism and hypoparathyroidism in an 11 year old boy with hemochromatosis
      secondary to aplastic anemia.
AB  - This is the first reported case, to our knowledge, of hypoparathyroidism and
      hypothyroidism due to secondary hemochromatosis with onset during childhood. The
      patient was a boy with refractory aplastic anemia in whom primary hypothyroidism
      and hypoparathyroidism became apparent at the age of 10 and 11 years old,
      respectively. He had received a total of 100 L of transfused blood by the age of
      10 years. The patient showed poor annual height gain due to primary
      hypothyroidism, together with hypocalcemia, cataract and intracranial
      calcification due to hypoparathyroidism. The early appearance of both thyroid and
      parathyroid dysfunction in this patient may have been due to the delay of
      initiation of iron-chelating agents and liver dysfunction due to hepatitis type
      C.

PMID- 7572162
TI  - Treatment of a stage I testicular yolk sac tumor with vascular invasion.
AB  - There is controversy concerning the treatment of stage I yolk sac tumor of the
      testis, particularly of those with histological factors that indicate a high risk
      of relapse. Usually orchiectomy alone is sufficient and adjuvant chemotherapy is
      unnecessary. Retroperitoneal lymphadenectomy is indicated for patients with
      persistently high alpha-fetoprotein. Once recurred, treatment at that time is
      thought to be curative. However, postoperative chemotherapy may be necessary for
      patients with a tumor expressing histological factors that predict possible
      relapse. In this paper we report on a case of a 2 year old boy whose tumor
      invaded the testicular veins. The patient suffered from recurrent disease but was
      successfully treated by chemotherapeutic regimens including cisplatin and
      retroperitoneal lymphadenectomy. The importance of the histological factors in
      making a decision on the treatment strategy for stage I testicular yolk sac tumor
      is discussed.

PMID- 7572163
TI  - Successful autologous bone marrow transplant for relapsed Ki-1 lymphoma.
AB  - We report on a 16 year old girl with relapsed Ki-1 lymphoma and a very poor
      prognosis. The initial manifestation was multiple bone metastases and
      lymphadenopathy. The patient achieved remission with modified adriamycin,
      bleomycin, vincristine, daunomycine therapy. However, 14 months after the
      completion of therapy, relapse occurred in a new cervical lymph node on the left
      side. After preparation with chemotherapy and total lymphoid irradiation (TLI)
      the patient underwent autologous bone marrow transplantation (A-BMT). Ki-1
      lymphoma shows clinically diverse symptoms, but hematopoietic stem cell
      transplantation should be performed in relapsed cases. It may be effective to
      give TLI followed by A-BMT for patients such as ours who have lymph node
      involvement without bone marrow metastasis.

PMID- 7572164
TI  - Promote breast feeding.

PMID- 7572165
TI  - Hypercholesterolemia and growth hormone in renal diseases.
AB  - The interrelationships of hypercholesterolemia, progression of renal disease to
      renal failure, and to risks of nephrotic syntrouse are emerging. Both
      hypercholesterolemia and growth hormone are progression factors, and, in the
      chronically nephrotic patient, these factors may help to explain the progression
      to renal failure. Treatment of such patients with growth hormone even though
      growth retarded should be approached with caution.

PMID- 7572166
TI  - Seroepidemiologic study of Helicobacter pylori infection in children in Taipei
      city.
AB  - To study the epidemiology of Helicobacter pylori (H. pylori) infection in
      children, the presence of the IgG antibody against H. pylori was evaluated by
      enzyme-linked immunosorbent assay (ELISA) method in unselected children in Taipei
      city. Serum samples were collected there from 428 apparently healthy children
      under 12 years of age. The overall prevalence of H. pylori infection was 8.4%. A
      low prevalence was found in the groups 1-3 years old (0.9%) and 3-6 years old
      (3.7%). The prevalence rate increased significantly after 6 years of age, and
      reached 19.4% at 9-12 years of age. In conclusion, H. pylori infection was
      independent of gender, but increased with age.

PMID- 7572168
TI  - Cerebral magnetic resonance imaging of preterm infants after corrected age of one
      year.
AB  - A total of 17 very-low-birth-weight (range from 625-1500 grams) preterm infants
      received brain magnetic resonance imaging (MRI) study at a mean corrected age of
      23 months (range from 15-33 months). They were classified into two groups. In
      Group 1 (12 cases) the cranial ultrasound study was normal during infancy. There
      were two cases with typical change of periventricular leukomalacia (PVL) detected
      by MRI study; both showed spastic diplegia. In Group 2 (five cases) ultrasound
      study was abnormal during infancy while the MRI confirmed the change of PVL in
      these cases whose ultrasound study showed typical change of PVL. In two cases of
      intraventricular hemorrhage (IVH) Grade I and III separately, the MRI also
      revealed the change of PVL, but only the case of IVH grade III had spastic
      diplegia. The myelination process of all cases were completed as normal term
      infants. In conclusion, brain MRI confirmed the PVL change discovered by cranial
      ultrasound and the results were strongly correlated with spastic type cerebral
      palsy. For those infants with an abnormal neurological examination, MRI may be
      useful for diagnosis of PVL in spite of normal ultrasound findings during the
      newborn period.

PMID- 7572167
TI  - Pediatric flexible bronchoscopy: a three-year experience.
AB  - One hundred and forty-one flexible fiberoptic bronchoscopies were performed in
      124 pediatric patients in Chang Gung Children's Hospital between October 1991 and
      September 1994. Eleven of these patients were younger than 1 month old; 52
      patients were younger than 1 year old; 94 patients were younger than 6 years old.
      The bronchoscope used was Olympus BF 3C20; with a 3.5 mm outer diameter, it also
      has a build-in 1.2 mm working channel. Most of the procedures were done in the
      pediatric intensive care unit. Oral chloral hydrate and parenteral benadryl were
      given as pre-sedation medication 30 minutes before the procedures; for most cases
      intravenous midazolam and meperidine hydrochloride were given immediately before
      the examination. The most common diagnoses were laryngomalacia, airway foreign
      bodies, subglottic stenosis or tracheal stenosis. Six episodes of transient
      hypoxemia and one brief episode of apnea were encountered. It was concluded that
      flexible fiberoptic bronchoscopy, very useful and safe in pediatric patients, has
      been underused in Taiwan.

PMID- 7572169
TI  - Outcome and cost of intensive care for very low birth weight infants.
AB  - Very low birth weights (VLBW) remain the major factor contributing to neonatal
      mortality and morbidity. The development of Neonatal Intensive Care Units (NICU)
      has improved the outcome for the VLBW infants. However, outborn VLBW infants may
      have different outcomes, and different medical costs than those born
      intramurally. This study compared the mortality, morbidity and costs of inborn
      and outborn VLBW infants cared in the NICU of a tertiary care center. A total of
      176 VLBW infants (inborn 83, outborn 93) were examined over the three years
      period June 1990 to May 1993. The birth weights (1131 +/- 244 g vs 1133 +/- 255
      g) and gestational ages (29.0 +/- 4.0 wk vs 28.9 +/- 3.0 wk) were not different
      between the two groups. However, the age of admission to our wards was
      significantly different between the inborn infants (5.0 +/- 3.2 hr.) and outborn
      infants (53.6 +/- 26.8 hr.). There was no difference in mortality rates between
      the outborn infants (35.7%) and the inborn infants (32.9%), nor in the incidence
      of intraventricular hemorrhage, respiratory distress syndrome, sepsis,
      necrotizing enterocolitis, retinopathy of prematurity or abnormal auditory
      brainstem response. However the incidence of patent ductus arteriosus and chronic
      lung disease of the outborn infants was higher than those of the inborn (47% vs
      32%, 51% vs 29% respectively). The mean duration of hospitalization and cost
      seemed to be longer and higher in the outborn VLBW infants. It was concluded that
      outborn VLBW infants have higher rates of morbidity, longer hospitalization and
      cost more than inborn infants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572170
TI  - Breast-feeding counseling by a 24-hour telephone hot-line.
AB  - A 24-hour telephone hot-line functioning as a counseling service and case
      registry was included in a multi-faceted breast-feeding promotion program. The
      mothers could speak directly to especially trained staff members in a municipal
      hospital. All the questions were answered according to an "Answering Book" which
      included the anticipated question and the optimum answer. A total of 201 calls,
      which included 340 problems, were recorded from January 1, 1993 to October 31,
      1993. Almost all the calls were made by the mothers (99%), and more than half
      (57.7%) of the mothers were primiparous. Most of the calls (79.6%) were made
      between 8 AM to 4 PM. The questions were frequently raised when the baby was aged
      8 to 14 days (23.4%). The most frequently asked questions were: (1) insufficient
      milk? (14.1%), (2) frequent and loose stools? (13.2%), (3) weaning? (10.3%), (4)
      drugs? (6.8%), (5) additional formula or water? (6.2%), and (6) maternal
      contraindication? (6.2%). Although the impact of this telephone consultation
      could not be properly evaluated, the incidence of breast-feeding during hospital
      stay increased from 50% to 73.4%, and breast-feeding for more than 1 month
      increased from 22.7% to 42.2% before and after the whole promotion program. It is
      recommended that health care professionals provide more help when the mother
      leaves the hospital. A nation-wide toll-free telephone operated by the Department
      of Health to increase the chance of successful breast-feeding is also
      recommended.

PMID- 7572171
TI  - Childhood leukemia mimicking juvenile rheumatoid arthritis.
AB  - Arthritis is a known manifestation of childhood leukemia. When it is the sole
      clinical finding, diagnosis of juvenile rheumatoid arthritis (JRA) may be
      impressed initially and hence delay diagnosis of the underlying malignancy. This
      review analysed the clinical pictures of six such patients whose acute
      lymphoblastic leukemia (ALL) was diagnosed after a variable period of delay,
      ranging from 2 weeks to 44 months. In general, initial articular and extra
      articular symptoms, and responses to conventional treatment, are not helpful in
      differentiating leukemic arthropathy from juvenile rheumatoid arthritis. However,
      the six ALL patients did have significantly less leukocytosis (6834 +/- 1586 vs
      13365 +/- 8039/mm3, p < 0.05) and relative lymphocytosis (61 +/- 17% vs 30 +/-
      13%, p < 0.05) on the initial hemograms when compared with JRA patient findings.
      JRA patients with initial hemograms showing less leukocytosis and relative
      lymphocytosis should be followed up with a high index of suspicion. Work-up for
      leukemia should be performed in any JRA patient with an evolving hemogram showing
      anemia, thrombocytopenia, leukopenia and lymphocytosis. Those who have an
      intractable clinical course necessitating immunosuppressive therapy should also
      receive bone marrow examination to obviate confusion in interpreting follow-up
      laboratory data. It can not be overemphasized that the differential diagnosis of
      acute leukemia should be made before JRA is impressed.

PMID- 7572172
TI  - The therapeutic outcome of medulloblastoma in 49 children.
AB  - The medical records of 63 patients with histologically-confirmed medulloblastoma
      were reviewed. From these, the clinical features and treatment outcome of 49
      patients were available for analysis. Following tumor resections, 44 patients
      were given craniospinal radiation therapy with local boosts to the posterior
      fossa and other macroscopically involved areas. Twenty patients received
      chemotherapy: 17 as postoperative adjuvant or salvage therapies, and 3 as
      preradiation chemotherapy. The postoperative early death occurred in two
      patients. The projected 5-year survival and recurrence-free survival rate of the
      overall group and the 41 patients who had completed radiotherapy were 61%, 70%
      and 50%, 57%, respectively. Two significant favorable factors were identified:
      complete tumor resection and combination radiotherapy. A better five-year
      survival rate was found in patients who had complete tumor resection (78% vs
      19%); with combination radiotherapy the rate was 70% vs 0%.

PMID- 7572173
TI  - Orbital cellulitis in children: clinical analysis of 16 cases.
AB  - Orbital cellulitis, defined as eyelid erythema and edema, proptosis and/or
      ophthalmoplegia, with or without visual acuity loss, is a rare, but severe
      infectious disease. The medical records were reviewed of 16 children, aged 18
      years or under, who were admitted at Chang Gung Memorial Hospital with a
      diagnosis of orbital cellulitis during the period from January 1977 to June 1993.
      The 16 children included 13 males and 3 females. The mean age of the patients was
      5.6 years. Sinusitis, diagnosed clinically and radiologically in eight cases, was
      the most common predisposing factor. From pus or blood in five patients, these
      pathogens were isolated: Staphylococcus aureus (2), viridans streptococci (1) and
      mixed bacterial flora (2). All of the patients were treated with systemic
      antibiotics. The mean duration of fever after initiation of antibiotic therapy
      was 2.9 days. Four patients subsequently developed complications: subperiosteal
      abscess (2), orbital abscess (1), and bacteremia (1). Five patients received
      surgical treatment. No mortality was reported. After a follow-up period of 1-2
      months, no sequelae were found among any of these 16 patients.

PMID- 7572174
TI  - Ultrasonic detection of single ectopic ureter inserted into the urethra in girls:
      report of two cases.
AB  - Two girls, each with a single ectopic ureter inserted into the proximal urethra,
      are reported. Abdominal ultrasonography showed that the involved kidneys were
      small and hydronephrotic. The associated ureters were dilated and opened into the
      proximal urethra. Diagnosis was confirmed by voiding cystourethrogram.

PMID- 7572175
TI  - Ureteropelvic fungal bezoar causing oliguric renal failure in a premature infant.
AB  - Systemic candidiasis with renal involvement is a relatively rare infectious
      process in young infants. The mortality rate in the cases reported to date has
      been lower after aggressive surgical and medical management. This report concerns
      a three-month-old, prematurely born infant with a fatal systemic candidiasis and
      acute renal failure. Renal pelvic fungal balls caused ureteropelvic junction
      obstruction in this patient. Renal ultrasonography demonstrated bilateral
      obstructive uropathy. Treatment consisted of surgical removal of the bezoar,
      together with open placement of nephrostomy tubes, parenteral amphotericin B
      therapy and peritoneal dialysis. This case emphasizes the need for a highly
      suspicion of renal obstruction by fungal balls in any high risk infant with
      systemic candidiasis and renal dysfunction.

PMID- 7572176
TI  - Neonatal coxsackievirus B1 infection associated with severe hepatitis: report of
      three cases.
AB  - Coxsackievirus B infection may cause fulminant disease in the neonate. In most
      reports the prominent symptoms have been recognized as myocarditis and
      meningoencephalitis, and a majority were caused by type B2 to B5. Coxsackie B1
      was a rare cause. From December 1993 to April 1994 three newborns were admitted
      to this Hospital with similar presentations of acute hepatitis and
      thrombocytopenia. Coxsackie B1 virus was isolated from all at one or two sites
      including rectal swab, throat swab and urine. One fatal case had had symptoms
      from birth; the disease progressed rapidly initially with a strikingly high liver
      enzyme; respiratory failure was noted; acute renal failure then happened later
      and the baby expired in two weeks. The other two patients survived, though one
      also had severe fulminant hepatitis. In that case onset of the disease was late
      at 28 days old. The other's clinical course was mild from the beginning.
      Myocarditis or central nervous system involvement were apparently not the
      significant presentations. Because the three babies all came from areas near this
      city (Chung-Ho and Pan-Chiao), attention should be drawn to the prevalence of
      coxsackie B1 virus infection in the total community.

PMID- 7572177
TI  - Refractory fetal supraventricular tachycardia with hydrops: report of one case.
AB  - Fetal tachycardia sometimes is quite difficult to treat, especially when the
      fetus has congestive heart failure. Sustained supraventricular tachycardia and
      hydrops had been diagnosed in a fetus as early as the 27th week of gestational
      age. A variety of antiarrhythmic agents, including digoxin, digoxin in
      combination with quinidine or propranolol or verapamil, have been prescribed for
      the mother, always in a vain effort of conversion of the tachycardia. A baby was
      born via vaginal delivery at 35 weeks' gestation because of premature labor. The
      tachycardia disappeared immediately after birth, but several episodes of
      tachycardia occurred during the neonatal period, and were converted only by
      electric cardioversion or intravenous amiodarone. Oral amiodarone was then
      prescribed for three months to prevent recurrence. The baby has lived well
      without attacks during a one-and-a-half-year follow-up.

PMID- 7572179
TI  - [Pharmacokinetics of contragestazol (DL-111-IT), a new non-steroid antifertility
      agent in monkeys].
AB  - The pharmacokinetics of contragestazol, an early pregnancy temperating agent [3
      (2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole, DL-111-IT] was studied in
      Rhesus monkey. The blood concentration of DL-111-IT was determined by coupled
      column system HPLC method. Using an aqueous vehicle (20% cremophor EL in saline)
      DL-111-IT was injected intravenously to monkeys at doses of 25, 12.5 and 6.3
      mg.kg-1. Blood drug concentration were measured. Using a programmable calculator
      the calculated pharmacokinetic parameters were as follows: alpha 1.83 h-1, 4.71 h
      1 and 3.61 h-1, beta 0.15 h-1, 0.08 h-1 and 0.09 h-1; T1/2 beta 6.63 h, 10.2 h
      and 10.1 h; AUC 9.54 micrograms.h-1.ml-1, 3.94 micrograms.h-1.ml-1 and 3.75
      micrograms.h-1.ml-1. An oil solution of DL-111-IT was injected intramuscularly in
      monkeys at doses of 50, 25 and 12.5 mg.kg-1. Its blood concentrations were
      determined at 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 and 24 h after
      administration. From the time vs concentration curve, the pharmacokinetic
      parameters obtained were as follows: Ka 0.98 h-1, 1.03 h-1 and 1.45 h-1; Ke 0.42
      h-1, 0.37 h-1 and 0.60 h-1; T1/2Ke 1.66 h, 1.90 h and 1.16 h; T (peak) 1.52 h,
      1.57 h and 1.09 h; AUC 4.86 micrograms.h-1.ml-1, 5.61 micrograms.h-1.ml-1 and
      1.74 micrograms.h-1.ml-1.

PMID- 7572178
TI  - Effects of Phytolacca acinosa polysaccharides I combined with interleukin-2 on
      the cytotoxicity of murine splenocytes against tumor cells.
AB  - Phytolacca acinosa polysaccharides I (PAP-I), a kind of purified polysaccharides,
      isolated from Phytolacca acinosa Roxb was found to significantly augment the
      cytotoxicity of murine splenocytes and interleukin-2 (IL-2) activated splenocytes
      against P815 tumor cells in vitro. The optimal concentration of PAP-I was 1
      microgram.ml-1 and the peak level of the cytotoxicity against P815 tumor cells
      was reached on d 3-5. The supernatants collected from splenocytes cultured with
      PAP-I alone or in combination with IL-2 showed no effect on the cytotoxicity
      against P815 tumor cells. Splenocytes from mice injected ip with PAP-I, 5, 10 and
      50 mg.kg-1, thrice a week produced more cytotoxicity against P815 and L929 tumor
      cells compared with the control group. PAP-I ip was shown to significantly
      increase IL-2 activated killer cell activity (LAK) against P815 tumor cells. The
      higher the dosage of PAP-I, the more potent the LAK activity was observed. These
      results confirmed that PAP-I can augment the cytotoxicity of murine splenocyte
      against tumor cells and LAK activity and warranted further evaluation of its
      clinical usefulness.

PMID- 7572180
TI  - [Inhibitory effect of tocainide on calcium current and potassium current in
      guinea pig ventricular myocytes].
AB  - In whole cell voltage clamp experiment with isolated guinea pig ventricular
      myocytes, tocainide was shown to exhibit a concentration-dependent inhibition of
      calcium current (ICa) and delayed rectifier potassium current (IK). Tocainide
      with a therapeutic concentration of 50 mumol.L-1 significantly inhibited the ICa
      and Itail (deactivating tail current of IK) by 16% and 3% respectively.
      Inhibition of ICa by tocainide was also shown to be dependent upon stimulating
      frequencies, with a greater blockade occurring at 2.0 Hz (57%) than at 0.2 Hz
      (17%). Tocainide was found to inhibit the IK,ATP by 74% at 200 mumol.L-1 but not
      at 50 mumol.L-1. These inhibitory effects on ICa and IK can probably explain the
      therapeutic effect of tocainide on supraventricular tachycardia, and the
      shortening of plateau phase of action potential.

PMID- 7572181
TI  - [Effect of ribavirin on NK activities of murine spleen cells in vitro].
AB  - The effects of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,
      RTC) on natural killer (NK) activities of murine spleen cells in vitro were
      studied by 125I-UdR isotope release assay. The results showed that RTC at the
      concentration of 5 mumol.L-1 significantly suppressed NK activities (P < 0.01),
      and a negative correlation between NK activities and RTC dosage was obtained. It
      also indicated that there was additive effect between the actions of RTC and
      dexamethasone (Dex, 1 mumol.L-1), and antagonism between the actions of RTC and
      interferon-gamma (100 U.ml-1). In addition, RTC at the concentration of 0.5
      mumol.L-1 was found to be enough to reduce the product of interferon (P < 0.01)
      and interleukin-2 (P < 0.05) induced by Con A in murine spleen cells, and a
      negative dose-effect relationship was observed. Thus, one of the mechanisms of
      RTC in inhibiting NK activities seems to suppress the production of these
      lymphokines.

PMID- 7572183
TI  - [Determination of the progesterone antagonist lilopristone in serum by RP-HPLC].
AB  - To 1.0 ml of serum containing lilopristone were added RU486 solution (internal
      standard, IS) and 1 ml of 1.0 mol.L-1 NaOH. The mixture was extracted with
      diethyl ether for 2 times. After extraction, the combined organic phase was
      evaporated to dryness and the residue was dissolved in the mobile phase and
      washed with petroleum ether. After centrifugation, 20 microliters of the lower
      layer was subjected to HPLC. A muBondapak-C18 (10 microns) column (30 cm x 3.9
      mm) was used and the column temperature was kept at 50 degrees C. The flow rate
      of mobile phase (methanol-dichloromethane--0.01 mol.L-1 phosphate buffer, pH 4.0,
      67:5:28 v/v) was 1.1 ml.min-1 and UV detection was performed at 302 nm. The
      retention times of lilopristone and IS were 6.85 and 9.07 min respectively and
      the detection limit was 10 ng.ml-1 (S/N > or = 4) serum. The extraction
      recoveries of lilopristone and IS were over 85%. The relative standard deviations
      were 2.21 to 4.23%. This method has been applied to study the pharmacokinetic of
      lilopristone in rats.

PMID- 7572182
TI  - [Pharmacokinetics of artenibenzoate in rats].
AB  - Artenibenzoate is a new schistosomacide. This paper reports the pharmacokinetics
      of artenibenzoate in rats after oral administration. The concentrations in
      biological samples were detected by spectrophotometry. The concentration-time
      curve of the drug in plasma showed a double-peak after 150, 300 and 600 mg.kg-1
      ig. Artenibenzoate absorption was fast and peak plasma level was found 1 h after
      administration. Then, the drug level declined to the lowest in 8 h. A second
      absorption peak appeared in 12 h. Two hours after oral administration to normal
      rats, the highest level of artenibenzoate was present in the stomach wall, while
      appreciable level was found in testicle, liver, spleen, heart, kidney and lung.
      Artenibenzoate in fat and intestine was lower, almost no drug was detected in
      brain and muscle. Six hours after oral administration, the drug concentration in
      various tissues decreased rapidly, but that in testicle, heart, kidney and fat
      decreased slowly. Urinary excretion was an important route of excretion.
      Artenibenzoate excreted in urine was about 45.6% of the administered dosage and
      that in feces 24.8% within a 48 hours period. The excreted amount in bile was
      0.54% within 36 hours. Plasma protein binding of artenibenzoate was about 70%.
      Major unchanged artenibenzoate was detected in the extract from plasma, major
      reduced-arteannuin from feces, and both unchanged artenibenzoate and reduced
      arteannuin from urine after oral administration in rats.

PMID- 7572185
TI  - [Pharmacokinetics and bioavailability of glipizide capsules].
AB  - The pharmacokinetics and bioavailability of glipizide were studied in 8 healthy
      male volunteers after a single oral dose of 5 mg in capsule or in tablet. The
      plasma levels of glipizide were assayed by high performance liquid
      chromatography. The concentration--time curves of both preparations were fitted
      to a one compartment model. The pharmacokinetic parameters of glipizide in
      capsule and in tablet were shown in tables 2 and 3. The relative bioavailability
      of the capsule was 109.9% compared with the tablet.

PMID- 7572184
TI  - [Studies on in vitro release kinetics of gentamicin sulfate
      polybutylcyanoacrylate nanoparticles].
AB  - The in vitro release characteristics of gentamicin sulfate polybutylcyanoacrylate
      nanoparticles were studied using a dialysis system comprising dialysis bag and
      receptor chamber. The whole apparatus was placed in a water bath shaker
      thermostated at 37 degrees C, and shaken at 50 cpm. The concentration of
      gentamicin in the receptor chamber was periodically determined by first
      derivative spectrometry. The results showed that the in vitro release of
      gentamicin sulfate from polybutylcyanoacrylate nanoparticles is
      characteristically biphasic, with an initial fast release (the burst effect),
      followed by a much slower release. These release profiles can be well modelled
      using a biexponential function. The related parameters of release kinetics have
      been calculated according to the biexponential function, and some factors that
      may affect the release characteristics were studied.

PMID- 7572186
TI  - [Gas chromatographic analysis of cannabinoids on tandem columns].
AB  - A simple, isotherm packed column gas chromatographic method was developed for the
      quantitative determination of neutral cannabinoids using 4-androstene-3,17-dion
      as internal standard. In order to achieve the best resolution and to avoid the
      evaluation of the disturbing hydrocarbon peaks a method was developed using
      "tandem" column made of 3% OV-1 (90%) and 3% OV-17 (10%) stationary phases. The
      psychotropic cannabinoids delta 1-tetrahydrocannabinol (delta 1-THC) and delta
      1(6)-tetrahydrocannabionol (delta 1(6)-THC), as well as, their main metabolites
      cannabidiol (CBD) and cannabichromene (CBC) were baseline separated except the
      cannabigerol (CBG) and cannabinol (CBN) pair, however for these compounds the
      separation was also satisfactory for the quantitative determinations. The Kovats
      retention indices were calculated for the most important cannabinoids and
      established the detection limits, respectively (20-50 ng range). The
      reproducibility was found excellent cv% = 1.06 for delta 1-THC and the analysis
      time was 55 minutes. The practical usefulness of the method was demonstrated by
      the comparative analyses on hashish- and fibre type hemps.

PMID- 7572187
TI  - Drug utilization study during pregnancy.
AB  - The history of drug registration in most developed countries has been strongly
      influenced by the dramatic thalidomide disaster. A systematic hand search
      identified all women who delivered between September 1st 1993 and June 1st 1994.
      A total of 2389 mothers were set against the Australian Classification of Drugs
      with respect to their known or suspected risks in pregnancy. According to the
      interview after delivery, and from the hospital files, the prescription rate of
      all drugs increased from 15% in period-1 (two months before pregnancy), to an
      average of 65.66% during pregnancy. We could divide the groups of drugs used
      during pregnancy into major and minor groups according to the number of women who
      ingested drugs in the different trimesters. 1. In the first trimester, women
      received major amounts of blood-forming drugs, vitamins and electrolytes,
      hormones, anxiolytics, antibiotics and GI drugs. 2. In the second trimester,
      women received major amounts of blood-forming drugs, vitamins and electrolytes,
      anti-infectives, anxiolytics, tocolytics and antihypertensive. 3. In the third
      trimester, women received major amounts of blood-forming drugs, vitamins and
      electrolytes, tocolytics, anxiolytics, anti-infectives, antithrombotics and
      antihypertensive. The drug groups mentioned above have been set according to it's
      decreasing use respectively.

PMID- 7572188
TI  - [Role of the family doctor in the complex treatment of early and late
      consequences of postmenopause. Effect of estrogen-progestogen on osteoporosis].
AB  - The physiology and pathology of menopause are discussed on the basis of data in
      the literature and based on the author's own long lasting experience. The
      advantages and disadvantages of oestrogenic and progestogenic treatments are also
      discussed. Factual knowledge on osteoporosis is summarized. The disease, its
      diagnosis and therapy and its occurrence (with special respect to the Hungarian
      situation) are also discussed.

PMID- 7572189
TI  - Titrimetric determination of captopril in dosage forms.
AB  - Two titrimetric methods are proposed for the determination of captopril in pure
      form or in tablets. In the first method iodide selective electrode is used for
      indirect titrimetric assay of captopril. This compound forms silver salt in
      presence of excess silver ions, the excess silver ions are determined
      potentiometrically with standardized iodide solution and an iodide selective
      electrode. The second method involves the titrimetric determination of captopril
      using a new oxidimetric titrant 2.3-dichloro-5.6-dicyano-1.4-benzoquinone (DDQ)
      in anhydrous acetic acid. The equivalent point is detected potentiometrically
      using calomel and platinum electrodes. The two methods allow semimicro
      determination of captopril, the results by the proposed procedures are in good
      agreement with those obtained by the official method.

PMID- 7572191
TI  - [Pharmacokinetic and metabolic studies in the development of drugs].
AB  - A system basing mainly on pharmacokinetic investigations has been elaborated by
      the author for the development of new drugs. The main elements of this system are
      as follows: 1.1. Screening toxicity investigations: Bacterial mutagenesis tests.
      Mammalian mutagenesis tests (These tests must be supported by kinetic studies in
      order to prove the exposure of the animals to the drug in negative cases, or to
      detect the critical plasma concentration of the drug in positive cases.)
      Cytochrome P-450 induction studies. In vitro metabolism studies (Incubation of a
      drug under development with rat, mouse, dog, rabbit and human liver microsomes
      (S9 fraction) can show the species (dis) similarities of the drugs. In vitro
      toxicology studies (The use of tissue cultures may answer the mechanism of
      toxicity. Early in vitro (eye and skin) irritation studies are of primary
      importance in the development of topical preparations. Acute toxicology studies
      (Acute toxicity investigations seem to become less important). 28 days (14 days)
      toxicity testing with pharmacokinetic measurements. 1.2. Long term and
      reproductive toxicity testing: The scientifically based evaluation of long term
      and reproductive toxicity studies can only be made in the light of toxicokinetic
      and metabolism data. 1.3. Human safety studies. Phase I. Study. The
      pharmacokinetic measurements must be made in order to see the (non) linearity of
      the kinetics as the function of dose. Phase II. Study. Pharmacokinetic
      measurements are necessary in order to establish the effective plasma (blood,
      serum) concentration of the drug. The pharmacokinetics of the drug should be
      determined in renal and liver patients, and in most of the cases in healthy
      elderly people.

PMID- 7572192
TI  - Spectrophotometric determination of etilefrine hydrochloride and ritodrine
      hydrochloride through nitrosation and subsequent cobalt chelation.
AB  - A simple and rapid method for the determination of etilefrine hydrochloride and
      ritodrine hydrochloride, either in pure form or in pharmaceutical formulations,
      is described. The method is based on the development of red product in presence
      of sodium nitrite and cobalt(II) salt in acid medium. The reaction is thought to
      proceed via preliminary nitrosation of the phenolic nucleus followed by formation
      of the chelate in presence of cobalt(II) salt. The highly colored chelates showed
      wavelengths of maximum absorption of 570 and 560 nm for etilefrine hydrochloride
      and ritodrine hydrochloride, respectively. The reaction product showed apparent
      molar absorptivities of 938 and 2930 L mol-1 cm-1 for etilefrine hydrochloride
      and ritodrine hydrochloride, respectively. A linear correlation was found between
      absorbance (at the lambda max) and concentration in ranges of 0.08-0.20 and 0.04
      0.10 mg ml-1 for etilefrine hydrochloride and ritodrine hydrochloride,
      respectively. At the same time, the resulting colors were well developed within
      25 min at boiling water bath temperature and were stable for more than 1 hr.
      Results of analysis of pure drugs and their dosage forms by the proposed method
      were in good agreement with either a reported derivative spectrophotometric
      procedure or the USP XXII method for etilefrine hydrochloride and ritodrine
      hydrochloride, respectively. The validity of the method was further confirmed
      using the standard addition method. The proposed method demonstrate high
      percentage of recovery with good accuracy and precision.

PMID- 7572190
TI  - Study of local anesthetics. Part 128. HPLC study of the degradation of heptacaine
      and carbisocaine in urine, human and rabbit serums.
AB  - A HPLC method is described for the simultaneous determination of the
      phanylcarbamate type anesthetics heptacaine and carbisocaine and their
      metabolites. Using this method the in vitro degradation of these drugs in urine,
      human and rabbit serums was investigated. The slower degradation of carbisocaine
      was explained on the basis of steric hindrance.

PMID- 7572194
TI  - Pharmaco-epidemiological study of drug consumption in the preproductive age
      period.
AB  - Based on the global hypothesis of drug consumption being a function of human age
      and growing with its increase, an analysis of that dependence was carried out in
      the preproductive interval of the human lifetime. The experiment included a total
      metropolitan population of 450,000, involving all outpatient prescriptions of all
      physicians in the area. The paper shows results obtained over a period of two
      years. The methodology, based on the expression of drug consumption in numbers of
      original package and in terms of financial costs, enabled to formulate the course
      of this dependence and to define its structure. It was found that preproductive
      age drug consumption shows a characteristically declining trend, progressively
      descending from a post-natal maximum to local minimums appearing in the 15-19
      year (costs), and 20-24 year (number of packages) age groups, respectively; in
      addition, it shows sex-specific differences and has the analytical shape of a 2nd
      degree polynomial. After the local minimums the curve begins to ascend according
      to the characteristic trend in the productive period of the human lifetime.

PMID- 7572193
TI  - [Lactate-guanidinium and lactate-lactate weak interactions in aqueous solutions].
AB  - Spectropolarimetry was used to quantify the guanidinium-lactate and lactate
      lactate equilibrium reactions. Association constants for the guanidinium-lactate
      and lactate-lactate formations are 6.11 and 1.12, respectively, in aqueous
      solution. The value 6.11 is certainly high among electrostatic interactions in
      water. This stability, however, can not account for the extremely strong lactate
      protein binding, observed by NMR spectroscopy. The molar rotation coefficients
      for both the heteroassociation and homoassociation complexes are also calculated.
      The homoassociative lactate-lactate binding is the first such interaction, whose
      constant has been determined by spectropolarimetry in aqueous solution.

PMID- 7572195
TI  - [Effects of calcium channel blockers on electrical and mechanical responses of
      rat phrenic nerve-diaphragm preparations].
AB  - The effects of diltiazem, prenylamine and verapamil on the electrical and
      mechanical responses of a rat phrenic nerve-diaphragm preparation were
      investigated as a function of the indirect stimulating frequency. The amplitude
      of the muscle compound action potential was depressed by all three drugs with
      stimulation between 3 and 50 Hz. The contractile force of the diaphragm was
      increased by these drugs in concentrations of 3 x 10(-8)-3 x 10(-5) mol/l at low
      frequency (3-10 Hz), but the contractility was decreased at higher concentrations
      (above 3 x 10(-5) mol/l). In contrast, a facilitating effect was not observed at
      a higher stimulating frequency (above 20 Hz), but a concentration depressant
      effect did develop above 1 x 10(-6) mol/l. The literature data and our results
      suggest that low concentrations of calcium channel blocking agents can not
      influence the trigger calcium current at low frequency (under 15 Hz), but calcium
      liberation and the contractile force are increased by these drugs. The
      intracellular calcium liberation triggered by the calcium current or the muscle
      force was inhibited by these drugs at higher concentrations. Above 15 Hz, the
      liberated intracellular calcium is insufficient for the contraction, so an
      adequate quantity of calcium is obtained from the extracellular space. It is
      suggested that an adequate calcium uptake is inhibited at low concentrations of
      these drugs at higher frequency, and the contractility is thereby inhibited.

PMID- 7572196
TI  - [Synthesis of potential CCK antagonist quinazolone derivatives].
AB  - An original route has been found for the synthesis of [1,4]diazepino
      quinazolones, a new ring system of heterocondensed quinazolones. These
      anthranilicacid-alanin-beta-alanin cyclopeptide derivatives constitute a
      structural moiety of asperlicin, the first natural cholecystokinin antagonist
      alkaloid. These compounds are therefore potential CCK antagonists. The new
      compounds were prepared via condensation of 2-amino-alkyl-quinazolones, obtained
      from 2-alkyl-quinazolones by side-chain substitution, with 1,3-bifunctional
      reagents. We studied the cyclisation process under basic, acidic and phase
      transfer catalyzed conditions. The structures of the synthesized compounds were
      characterized by IR, UV and NMR spectroscopy.

PMID- 7572197
TI  - Synaptic vesicles and release of transmitters: new insights at the molecular
      level.
AB  - Neurotransmitter release from transmitter storage vesicles is a regulated
      signalling event that has properties in common with other secretory systems.
      Biochemical characterization of mammalian synaptic vesicle proteins has recently
      converged with studies of protein traffic in non-neuronal cells and the genetic
      dissection of the yeast secretory pathway to give us a considerable amount of new
      data. Many new synaptic vesicle proteins have been characterized together with
      plasma membrane proteins with which they interact, and it appears that many of
      the participating components may be part of a general machinery for secretion.
      The new results significantly improve our understanding of the molecular
      mechanisms governing transmitter release. This review discusses the recent
      progress in terms of synaptic vesicle components and the proposed mechanisms for
      exocytosis.

PMID- 7572198
TI  - Effect of different xanthines and phosphodiesterase inhibitors on c-fos
      expression in rat striatum.
AB  - It has previously been shown that caffeine, in a dose-dependent manner, increases
      the expression of the protooncogene c-fos in the rat brain, predominantly in the
      caudate-putamen and tuberculum olfactorium. In this study we examined the effect
      of related xanthines and of selective phosphodiesterase inhibitors on c-fos
      expression. The effect of caffeine (75 mg kg-1) was mimicked by 3-isobutyl-1
      methyl xanthine (IBMX) (25 mg kg-1) and theophylline (100 mg kg-1) but not by 8-p
      sulfophenyltheophylline (10 mg kg-1), enprofylline, theobromine or paraxanthine
      (each at 100 mg kg-1). Moreover, the cyclic AMP-selective phosphodiesterase
      inhibitors rolipram (10 or 20 mg kg-1) and SQ 20,006 (25 mg kg-1) and the cyclic
      GMP-selective phosphodiesterase inhibitor zaprinast (10 mg kg-1) failed to induce
      c-fos in striatum, but caused a clear-cut induction in the overlying cerebral
      cortex. Thus, c-fos is induced in rat striatum following administration of
      caffeine and other xanthines that (provided they enter the brain) block adenosine
      receptors, suggesting an involvement of central adenosine receptors. Inhibition
      of cyclic nucleotide phosphodiesterase does not appear to play any important role
      in c-fos induction by the xanthines.

PMID- 7572199
TI  - Ethanol inhibits NMDA-induced toxicity and trophism in cultured cerebellar
      granule cells.
AB  - In cerebellar granule cell cultures, glutamate and N-methyl-D-aspartate (NMDA)
      caused either neurotoxic or trophic effects, depending on the developmental stage
      of the neurones. Ethanol (100 mM) partly inhibited delayed neurotoxicity induced
      by the excitatory amino acids (25 microM glutamate for 15 min or 100 microM NMDA
      for 30 min) assessed 24 h after the incubations in mature cultures in the absence
      of Mg2+. Glycine (5 microM) potentiated the toxicity of glutamate and the ethanol
      inhibition, and was routinely added in these experiments. The viability of
      neurones in the presence of 25 mM K+ and 0.8 mM Mg2+ was not impaired when
      maintained in 40-50 mM ethanol for the whole culture period of 7 days. However,
      ethanol almost completely inhibited the trophic effects of NMDA on developing
      cultures in 12.5 mM K+/0.8 mM Mg2+ medium. Glutamate (25 microM) and NMDA (100
      microM) potently induced 45Ca2+ uptake by granule cells from day 2 in vitro
      onward. Sixty-five per cent of the 15-min 45Ca2+ influx induced by glutamate and
      80% of that induced by NMDA were inhibited by ethanol (100 mM). MK-801 (a non
      competitive antagonist of NMDA receptors; 100 nM) completely inhibited the toxic
      and trophic actions of glutamate and NMDA, as well as the 45Ca2+ influx induced
      by NMDA, but only 80% of the 45Ca2+ influx induced by glutamate. These results
      show that the toxic and trophic actions of glutamate are mediated mainly by Ca2+
      influx through NMDA receptors. Both of these actions and the underlying Ca2+
      influx are significantly inhibited by ethanol at pharmacological concentrations
      (< or = 100 mM), although the mechanisms of inhibition still need further study.

PMID- 7572200
TI  - Atrial natriuretic peptide and its mRNA in heart and brain of vasopressin
      deficient Brattleboro rats.
AB  - To understand the secretion and synthesis of atrial natriuretic peptide we
      measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and
      brain areas, and ANP mRNA was determined from heart auricles and ventricles of
      vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated
      Brattleboro rats (DI+DDAVP). Long-Evans rats (LE) served as controls. DI+DDAVP
      rats were given for 3 days sc. injections of 0.5 micrograms 1-desamino-8-D
      arginine vasopressin in 1 mL saline twice a day. The rats were housed in single
      metabolic cages and urinary output and water intake were measured daily. All the
      body and organ weight parameters were similar in the three groups when the rats
      were killed. No change was seen in the plasma ANP level between the groups. The
      right ventricle of DI+DDAVP rats had significantly (P < 0.05) higher
      concentration of ANP than LE rats (15.8 +/- 4.4 vs. 3.4 +/- 0.6 ng mg-1 tissue).
      The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts
      of ANP mRNA than LE rats (0.5 +/- 0.2 vs. 1.3 +/- 0.2 and 0.5 +/- 0.1 vs. 1.3 +/-
      0.2 arbitrary units). In the hypothalamus, the ANP concentration was
      significantly (P < 0.05) lower both in DI and in DI+DDAVP rats than in LE rats
      (9.3 +/- 1.3 vs. 14.5 +/- 1.6 and 6.1 +/- 0.6 vs. 14.5 +/- 1.6 pg mg-1 tissue).
      To conclude, although the water intake and urinary output of DI rats were changed
      towards normal with desmopressin treatment, the heart ventricular and
      hypothalamic ANP did not parallel the change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572201
TI  - Sympathetic reinnervation of unilaterally denervated rat lung.
AB  - The effect of unilateral sympathetic denervation and reinnervation of the lung on
      a variety of circulatory parameters was investigated in urethane-anaesthetized
      rats. The left main stem bronchus together with its surrounding nerves was cut
      and reanastomosed in 40 rats: 12 intact rats served as controls. Final
      experiments were performed after 0 days to 10 months: the left stellate ganglion
      was stimulated. The effect was greatest at 20 Hz. Pulmonary arterial pressure
      increased significantly (P < 0.05) by 10% and pulmonary flow decreased
      significantly (P < 0.05) by 16% in the control rats; no effect on these
      parameters was found in acutely denervated rats. The stimulus-elicited change in
      pulmonary arterial pressure reappeared 1 week after unilateral hilar stripping
      and gradually returned during reinnervation. After 10 months, the increase in
      pressure was significantly (P < 0.05) larger than that of the control by 50%,
      whereas the noradrenaline content of the reinnervated lung was significantly (P <
      0.05) smaller than that of the intact side by 48%. This discrepancy may reflect
      denervation hypersensitivity of vascular muscle cells. The operations had no
      effect on systemic circulation: heart rate and systemic arterial pressure
      increased and aortic blood flow decreased to the same extent in all experimental
      groups during nerve stimulation. These results suggest that sympathetic
      reinnervation of the rat lung starts within 1 week but that reinnervation is
      still incomplete 10 months after unilateral hilar stripping.

PMID- 7572202
TI  - Plasma atrial natriuretic peptide in standardbred and Finnhorse trotters during
      and after exercise.
AB  - To study the exercise-induced changes in atrial natriuretic peptide (ANP), a
      hormone with cardiovascular and renal effects, an incremental submaximal exercise
      test on a high-speed treadmill was carried out with Standardbred and Finnhorse
      trotters, the former bred for speed and the latter originally for heavy work.
      Standardbreds performed the 2 min exercise intervals at speeds of 6, 7, 8, 9 m s
      1 and Finnhorses, according to their training status, at 5, 6, 7, 8 m s-1, 4, 5,
      6, 7 m s-1 or 5, 6, 7 m s-1. Steady-state heart rate (HR) was reached within each
      2 min interval. The increase in HR was linear and proportional to work intensity
      and physical condition and it peaked, average 204 beats min-1, during the last
      speed of the treadmill. Plasma ANP increased significantly and equally, by 27 +/-
      4 pg mL-1, in both breeds and peaked at 5 min post-exercise. The rise in ANP
      during exercise showed good linearity with HR and increasing work intensity. The
      decrease of ANP after exercise was slow, which may be connected to the regulation
      of water and electrolytes. Interbreed differences in plasma ANP were not
      observed. The results suggest a role of ANP in cardiovascular control and fluid
      balance during and after exercise. In addition to other possible releasing
      factors during exercise, the increase in HR explains about 40% of the variability
      in the plasma ANP values.

PMID- 7572203
TI  - Effects of age on sarcoplasmic reticulum properties and histochemical composition
      of fast- and slow-twitch rat muscles.
AB  - Calcium release activity of sarcoplasmic reticulum and enzyme-histochemical
      properties were investigated in extensor digitorum longus (e.d.l.) and soleus
      muscles in young (4 months and old (24 months) male rats. With age, the caffeine
      threshold concentration for calcium release from the sarcoplasmic reticulum of
      soleus skinned muscle fibres showed only minor modifications. On the other hand,
      in e.d.l. skinned muscle fibres, the caffeine threshold concentration decreased
      significantly (P < 0.05). The histochemical fibre type composition changed with
      age both in soleus and in e.d.l. muscles, showing a common transformation toward
      a more oxidative histochemical profile. In fact, in aged soleus, a significant (P
      < 0.05) increase was observed of type 1 fibres to represent almost the totality
      of the muscle fibres (more than 98%), while types 2C and 2A were reduced in
      proportion. In aged e.d.l. the percentage of type 1 (P < 0.05), 2A and 2X (a
      recently identified fourth component of the fast-twitch muscle types) fibres
      increased, with a reduction of type 2B (P < 0.01) fibres. The present results
      suggest that the changes in contractile properties of aged muscles may be related
      to the changes not only in fibre composition but also in the mechanism of calcium
      release from sarcoplasmic reticulum.

PMID- 7572204
TI  - Role of glucose metabolism and phosphoinositide hydrolysis in glucose-induced
      sensitization/desensitization of insulin secretion from mouse pancreatic islets.
AB  - The role of glucose metabolism and phosphoinositide hydrolysis in glucose-induced
      sensitization/desensitization of insulin secretion was studied. A change in
      glucose concentration from 5.5 to 16.7 mM during 22-24 h of pre-exposure of mouse
      islets in TCM 199 culture medium (0.26 mM Ca2+) led to sensitization of glucose
      induced insulin secretion. This change in islet responsiveness to glucose was not
      mediated by increases in glucose utilization ([5-3H]glucose conversion to 3H2O)
      and glucose oxidation ([U-14C]glucose oxidation to 14CO2). Glucose-induced
      sensitization of insulin secretion was associated with an increase in glucose
      induced phosphoinositide hydrolysis, leading to a significant increase in
      inositol 1-monophosphate formation, but not in inositol 1,4-bisphosphate or in
      inositol 1,4,5-trisphosphate plus inositol 1,3,4-trisphosphate formation.
      Diacylglycerol, which may arise from both phosphoinositide hydrolysis and de novo
      from glucose metabolism, was, on the other hand, not increased during acute
      exposure to glucose and not changed after pre-exposure to glucose. At 16.7 mM
      glucose in TCM 199 medium, a change in Ca2+ concentration from 0.26 to 1.26 mM
      led to a reduction in glucose-induced insulin secretion. This Ca(2+)-dependent
      desensitization of insulin secretion in the presence of glucose was associated
      with a decrease in glucose-induced phosphoinositide hydrolysis, but not with a
      change in glucose metabolism or diacylglycerol accumulation. In conclusion, it is
      suggested that glucose-induced sensitization/desensitization of insulin secretion
      may involve changes in phosphoinositide hydrolysis, but may occur independently
      of concomitant changes in glucose metabolism or diacylglycerol accumulation.

PMID- 7572205
TI  - Strain difference in early postnatal sleep-wake behaviour between Alko Alcohol
      and Wistar rats.
AB  - Early postnatal sleep-wake behaviour of male and female rats of Alko Alcohol and
      Wistar strain was studied using a static charge sensitive mattress when the rats
      were aged 1 and 2 weeks postnatally. In both strains and sexes, waking time
      relative to total recording time increased, proportion of quiet state did not
      change, and that of active sleep decreased during the second postnatal week. The
      number of long active sleep stages relative to short active sleep stages and the
      duration of sleep-wake stages increased with age. Transitions between quiet state
      and active sleep became fewer with increasing age. Waking time increased more in
      Wistar rats than in Alko Alcohol rats. At 1-2 weeks of age, the percentage of
      active sleep and the number of long active sleep stages relative to short active
      sleep stages were larger, and the duration of sleep-wake stages longer in Alko
      Alcohol than in Wistar rats. Sleep-wake behaviour did not differ between the
      sexes of either strain or age. Selective breeding for high alcohol preference in
      Alko Alcohol rats may have caused a genetic trait in early postnatal sleep-wake
      behaviour.

PMID- 7572206
TI  - Modulation of systolic and diastolic function by endothelin-1: relation to
      coronary flow.
AB  - Different conclusions have been reached with regard to the effect of endothelin
      (ET-1) on cardiac contractility. We examined systolic and diastolic function in
      response to constant known concentrations of ET-1 with or without ET-1 induced
      reductions in coronary flow (CF). Rat hearts (n = 21) were buffer-perfused using
      constant coronary flow (cCF) or constant perfusion pressure (cPP). Left
      ventricular function was assessed isovolumically. Addition of ET-1 (10(-9) M) in
      the cCF group caused a gradual increase in PP from 61 +/- 2 to 165 +/- 6 mmHg
      (mean +/- SE) (P < 0.01). Within 10 min left ventricular systolic pressure (LVSP)
      increased from 111 +/- 2 to a maximum of 134 +/- 4 mmHg (P < 0.01) and [LVdP/dt]
      increased from 1640 +/- 81 to a maximum of 2020 +/- 92 mmHg s-1 (P < 0.01). After
      15 min left ventricular end diastolic pressure (LVEDP), a measure of diastolic
      stiffness (DS), also increased. With ET-1 (10(-8) M), similar haemodynamic
      alterations appeared more rapidly. In the cPP group, ET-1 (10(-9) M) caused a
      sharp decrease in CF and LVSP fell from 115 +/- 8 to 62 +/- 12 mmHg at 10 min (P
      < 0.001). Systolic function remained stable at a reduced level for 1 h. DS did
      not change. Thus, ET-1 possesses positive inotropic effects and increases
      diastolic stiffness. Both effects may be masked by vasoconstriction-induced
      ischaemia.

PMID- 7572207
TI  - Endothelium-dependent rhythmic contractions induced by cyclopiazonic acid, a
      sarcoplasmic reticulum Ca(2+)-pump inhibitor, in the rabbit femoral artery.
AB  - The vascular responses to cyclopiazonic acid (CPA), an inhibitor of the Ca(2+)
      ATPase in the sarcoplasmic reticulum, were investigated in the rabbit femoral
      artery, suspended in an organ chamber for isometric tension recordings. CPA
      produced rhythmic contractions in the femoral artery which had been contracted
      with phenylephrine. CPA, however, did not induce the rhythmic responses in
      endothelium-denuded arteries. NG-nitro-L-arginine methyl ester and methylene
      blue, inhibitors of the formation and the action of nitric oxide, respectively,
      failed to antagonize the CPA-induced rhythmic contractions in the phenylephrine
      contracted artery. In contrast, the CPA-induced rhythmic contractions were
      abolished by charybdotoxin, a Ca(2+)-activated K+ channel antagonist, but not by
      glibenclamide, a blocker of the ATP-sensitive K+ channel. Nifedipine also
      inhibited the CPA-induced rhythmic contractions in the endothelium-intact artery
      and relaxed the endothelium-denuded artery treated with CPA. These results
      indicate that the CPA-induced rhythmic contractions in the phenylephrine
      contracted rabbit femoral artery may be attributed to the periodic inactivation
      of the voltage-dependent Ca2+ channel, presumably regulated by the Ca(2+)
      activated K+ channel. The activation of the K+ channel by CPA might occur only
      when the endothelium is present.

PMID- 7572208
TI  - Influence of cerebrovascular sympathetic, parasympathetic, and sensory nerves on
      autoregulation and spontaneous vasomotion.
AB  - The effect of removal of cerebrovascular sympathetic, parasympathetic or sensory
      nerve on brain cortical blood flow and spontaneous vasomotion during changes in
      systemic blood pressure was studied by laser-Doppler flowmetry in anaesthetized
      rats. Selective section of sympathetic fibres along the internal carotid artery
      markedly affected the ability to autoregulate, as measured in microvessels of the
      middle cerebral arterial territory. Removal of the parasympathetic nerves tended
      to reduce the ability to autoregulate, whereas no significant influence was found
      after sensory denervation. Following the denervations, spontaneous vasomotion was
      not significantly affected in frequency or amplitude.

PMID- 7572209
TI  - Pronounced and rapid plasma volume reduction upon quiet standing as revealed by a
      novel approach to the determination of the intravascular volume change.
AB  - Plasma volume (PV) changes to 15 min quiet standing were analysed (Hb/Hct
      alterations) in two studies (nine and 11 healthy males). Data confirmed and
      extended our findings that blood, arterial or venous, sampled on standing fails
      to reveal the induced overall haemoconcentration (PV loss). First, standing led
      to markedly incomplete mixing of blood between circulatory compartments.
      Secondly, with sampling of antecubital venous blood, haemoconcentration was
      strongly affected by regional plasma loss and, apparently equally important, by
      regional blood flow. These difficulties were circumvented, however, by the
      finding that the PV restitution (haemoconcentration) in the recumbent subject
      after standing fitted invariably a monoexponential function with striking
      precision. It allowed, by extrapolation, a seemingly superior definition of the
      PV reduction at the very end of standing as supported by the fact that PV changes
      from Hb/Hct and from IgM protein concentration changes were similar, refuting
      that Fcell-changes contributed to the pronounced Hb/Hct changes. The described
      novel approach revealed a nicely reproducible PV loss of no less than 692 +/- 46
      mL (18.1 +/- 0.6%, Study I; 18.4 +/- 0.5%, Study II), or approximately 11%
      reduction of blood volume, showing that quiet standing leads to a much more rapid
      and haemodynamically important decrease in PV than reported previously. Yet, PV
      was virtually restored within 20 min of recumbency after standing, with 50%
      recovery within 6 min and regain of as much as 70 mL in the very first min. The
      latter data indicate that the body possesses a surprising capacity for rapid
      fluid transfer from the extra- to the intravascular space.

PMID- 7572210
TI  - Electrophysiological study of blink reflex in humans: differences in mental and
      supraorbital nerves.
AB  - In order to find an explanation for the discrepancy between previous reports on
      the consistency of the blink reflex response with stimulation of the mental
      nerve, the habituation of the blink reflex was studied with stimulation of the
      supraorbital and mental nerves in 14 healthy adults. A series of eight electrical
      stimuli was delivered to the distributions of the nerves on each side at
      frequency rates of 1.0, 0.5, 0.2 and 0.1 Hz. The latencies and peak-to-peak
      amplitudes of the ipsilateral late blink reflex components (R2i) were measured.
      The habituation phenomenon was analysed by means of multivariate analysis of the
      amplitudes, the nerve and frequency effects were determined by means of a
      repeated measures analysis of variance model. The blink reflex showed more
      pronounced amplitude attenuation of the consecutive responses with stimulation of
      the mental than the supraorbital nerve at rates of 0.5 and 0.2 Hz, and marginally
      so also at 0.1 Hz. For the supraorbital nerve, habituation could be demonstrated
      with stimulation frequencies of 1.0 and 0.5 Hz, while for the mental nerve a
      statistically significant habituation phenomenon was found even with the lowest
      repetition rate of 0.1 Hz. The greater tendency of the mental nerve blink reflex
      to habituate is obviously one reason why it has previously sometimes been
      considered too inconsistent to be useful in clinical practice. For the recording
      of the supraorbital nerve blink reflex, a 10 s interval between stimuli is
      adequate, whereas longer interstimulus intervals may have to be adopted to obtain
      consistent blink reflex responses with stimulation of the mental nerve.

PMID- 7572211
TI  - Differential locations in the midbrain of distinct groups of vertical eye
      movement-related neurones in cat: their projections and direct connections with
      oculomotor neurones.
AB  - The present study was undertaken to investigate the firing patterns, location and
      projections of vertical eye movement-related neurones in the Forel's field H
      (FFH), the interstitial nucleus of Cajal (INC), and reticular formation of the
      mesodiencephalic junction (MDJ) in chronically prepared alert cats. A total of
      456 neurones in the medial MDJ with firing closely related to vertical eye
      movements was examined using antidromic microstimulation and spike-triggered
      averaging technique. On the basis of their firing patterns, these neurones were
      classified into five groups, i.e. burst neurones (BNs), burst-tonic neurones
      (BTNs), tonic neurones (TNs), augmenting neurones (ANs) and pause neurones (PNs).
      BNs were located mainly in the dorsomedial part of the FFH. Most of TNs were
      found more caudally than BNs. BTNs and PNs were located further caudally, within
      the INC and nearby reticular formation. ANs were located mainly in the
      dorsolateral part of the FFH. Both medium-lead BNs (MLBNs) and BTNs projected to
      the inferior rectus (IR) subdivision of the oculomotor nucleus on both sides.
      MLBNs projected to the trochlear nucleus as well through collateral branches of
      the axon projecting to the oculomotor nucleus. Downward and upward MLBNs made
      direct excitatory and inhibitory connections, respectively, with IR
      motorneurones. These results suggest that many kinds of neurones in the
      paramedian regions of MDJ play a significant role in the genesis of vertical eye
      movements.

PMID- 7572213
TI  - Ovarian levels of epidermal growth factor receptor mRNA in the rat--a
      postovulatory decrease.
AB  - Members of the epidermal growth factor (EGF) family have many different effects
      on ovarian cells including a strong inhibition of estradiol-17 beta production.
      An increased binding of the EGF family to its receptor is seen at the time of
      ovulation. The aim of the present study was to measure the mRNA levels of the EGF
      receptor in the preovulatory follicle and to see if the levels are still high
      after functional luteolysis. The mRNA of the EGF receptor was measured in whole
      ovaries, follicles and corpora lutea. Pregnant mare serum gonadotrophin (PMSG)
      stimulated rats were used to get defined follicles. To achieve luteolytic corpora
      lutea on day 11, the adult female pseudopregnant rat model was used.
      Determination of the EGF receptor mRNA was performed with solution hybridization
      analysis, using a 768 bp long probe of the human EGF receptor (2318-3085). A two
      fold increase in the mRNA levels of the EGF receptor was registered between 09.00
      and 21.00 h during the proestrus day in the preovulatory follicle. Concurrently,
      serum estradiol-17 beta levels decreased from 420 +/- 65 to 79 +/- 6 pM. High
      levels of EGF receptor proteins in the preovulatory follicle were verified by
      immunohistochemistry. The levels of EGF receptor mRNA was decreasing from 25.4 +/
      4.4 fmol mg-1 in the corpus luteum on day 1 to 7.6 +/- 9.9 fmol mg-1 on day 11.
      Thus, the high amounts of EGF receptor in the ovary during the late preovulatory
      period might be involved in the regulation of ovarian estradiol-17 beta
      production.

PMID- 7572212
TI  - Interaction between 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20
      one in the control of neuronal excitability in slices from the CA1 hippocampus in
      vitro of guinea-pigs and rats.
AB  - The effect of 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20-one
      (allopregnanolone) on the action potentials in the Schaffer collateral pathway
      was investigated in hippocampus CA1. Slices from male and female guinea-pigs and
      female rats were used. In the rat three groups were studied: (a) untreated
      prepubertal rats at day 25 after partus; (b) rats injected on day 26 with 10 IU
      of equine serum gonadotropin studied on day 28, when in the pro-oestrus
      follicular phase; and (c) on day 32 when in the luteal phase. The
      allopregnanolone (12.6 microM, 0.5 nL) was applied locally in stratum
      orienspyramidale. the 17 beta-oestradiol (0.7 nM) was perfused (4 mL min-1) or
      applied locally. The amplitude of the population spike in stratum pyramidale was
      increased by oestradiol in guinea-pigs of both sexes and in all the three groups
      of rats. Allopregnanolone decreased the amplitude of the population spike in the
      guinea-pigs and in the luteal phase rats. The effect appeared within seconds
      after the application of the drugs. The allopregnanolone inhibition of the
      population spike was increased by perfusion with oestradiol in the guinea-pigs
      and in the luteal phase rats. This effect appeared within 7 min, and improved
      with increasing length of the perfusion (7-71 min). It remained for 55 min after
      return to perfusion with artificial cerebrospinal fluid. In prepubertal and
      follicular phase rats the allopregnanolone inhibition was seen only after
      perfusion with oestradiol for more than 15 min. The results show that 17 beta
      oestradiol increases the allopregnanolone inhibition and that this inhibition is
      most efficient during the luteal phase of the rat.

PMID- 7572214
TI  - Cerebral energy metabolism during hypoxaemia. A 31P and 1H magnetic resonance
      study.
AB  - By means of proton and phosphorous magnetic resonance spectroscopy at 1.5 Tesla
      the human cerebral metabolism was investigated during mild and moderate
      hypoxaemia. Seven volunteers participated and spectra were obtained while the
      subjects were breathing atmospheric air, 16, 12 and 10% oxygen in N2.PaO2, PCO2
      and arterial oxygen saturation were determined during the spectroscopic
      measurements. Haemodynamic and respiratory mechanisms compensated the hypoxic
      condition and no lactate production was found. There was no change in N-acetyl
      aspartate. No change in intracellular pH was found. A slight but non-significant
      decrease in PCr/P(i)-ratio was found, indicating a decrease in the
      phosphorylation potential of the brain in response to hypoxaemia. The brain
      sustains aerobic metabolism during mild to moderate hypoxaemia.

PMID- 7572215
TI  - Release of somatostatin, neurotensin and vasoactive intestinal peptide upon
      inhibition of gastric acid secretion by duodenal acid and hyperosmolal solutions
      in the conscious rat.
AB  - The inhibitory effect of duodenal exposure to acid and hyperosmolal solutions on
      pentagastrin-stimulated gastric acid secretion was studied in conscious rats
      equipped with chronic gastric fistula and duodenal Thiry-Vella loop. The loop was
      challenged with saline, HCl or hyperosmolal polyethylene glycol. Gastric acid
      secretion was measured in samples from the gastric fistula. Gut peptide
      concentrations were measured in duodenal perfusates collected each 30 min, and in
      plasma samples collected both during stimulated acid secretion alone, and at the
      end of experiments in combination with luminal challenges of the loops. During
      pentagastrin-stimulated gastric acid secretion, luminal perfusion of the duodenal
      loop with acid caused inhibition of acid secretion (P < 0.001) and a prominent
      release of somatostatin both to the lumen (P < 0.001) and to the circulation (P <
      0.05). Also, neurotensin (P < 0.01) and vasoactive intestinal peptide (P < 0.01)
      were released to the lumen, but not to the circulation. Upon perfusion of the
      duodenal loop with hyperosmolal polyethylene glycol, acid secretion was inhibited
      (P < 0.05) and somatostatin alone was released to the luminal side (P < 0.01). In
      conclusion, duodenal exposure to acid inhibits pentagastrin-stimulated gastric
      acid secretion and releases SOM to the circulation that may directly inhibit acid
      secretion. Concomitantly, somatostatin (SOM), neurotensin and vasoactive
      intestinal peptide are released to the lumen. Duodenal exposure to hyperosmolal
      polyethylene glycol inhibits acid secretion with a luminal release of SOM only.
      Thus, luminal acid and hyperosmolal solutions inhibit gastric acid secretion by
      separate mechanisms. After acid or hyperosmolal challenge, the release of SOM to
      the circulation indicates gastric acid inhibition in an endocrine manner, while a
      luminal release of gut peptides indicates a local peptide overflow that might be
      of importance via paracrine regulatory mechanisms in the intact animal.

PMID- 7572216
TI  - Circadian periodicity in salivary carbonic anhydrase VI concentration.
AB  - Carbonic anhydrase VI (CA VI) is secreted into the saliva by the serous acinar
      cells of the parotid and submandibular glands. Saliva samples from six healthy
      male volunteers were analysed for concentrations of CA VI throughout the 24 h
      period by means of a specific time-resolved immunofluorometric assay and the
      levels were compared with amylase activity. The sleeping period was from 00.10 h
      to 07.30 h and the subjects had breakfast at 07.30 h and regular meals at 13.30 h
      and 19.30 h. Saliva secretion decreased markedly during the sleeping period in
      all the subjects except one. The levels of both CA VI and amylase activity varied
      greatly among the subjects, but in a parallel manner, and declined to a very low
      level during the sleeping period. Dexamethasone intake at midnight had no effect
      on the morning rise in either enzyme. When the sleeping period was postponed from
      06.10 h to 11.30 h both enzyme concentrations declined during the night and
      continued to be low until the subjects awoke at 11.30 h, whereas salivary
      secretion was low only during the sleeping period. Our results suggest that CA VI
      secretion follows a circadian periodicity that is comparable to amylase secretion
      but independent of salivary secretion.

PMID- 7572217
TI  - Vagal nerve stimulation of the guinea-pig oesophagus.
AB  - Vagal nerve stimulation of the isolated guinea-pig oesophagus resulted in a
      triphasic contractile response which was abolished by tetrodotoxin. The
      mechanisms for each of the three responses were investigated. The first response
      was abolished by the neuromuscular blocking drug, tubocurarine, and was
      unaffected by atropine. The second response to vagal nerve stimulation was
      abolished by the ganglion blocking drug, hexamethonium, and by tubocurarine at a
      higher concentration than that required to block the first response. The second
      response was also abolished by atropine and was enhanced by physostigmine. It was
      concluded that this response was due to preganglionic stimulation of smooth
      muscle. omega-Conotoxin GVIA selectively inhibited the third response. This
      response was resistant to the neuromuscular and ganglion blocking drugs yet was
      abolished by atropine and was enhanced by physostigmine. This implicates the
      involvement of cholinergic neurones activated independently of nicotinic
      ganglionic receptors. The third response was also selectively abolished by
      capsaicin and enhanced by thiorphan. Contractile responses resulting from
      exogenous substance P were abolished by atropine and tetrodotoxin and enhanced by
      physostigmine. These findings suggest that the third response may be mediated by
      the action of a substance P-like neuropeptide released from sensory nerve endings
      which subsequently activate cholinergic neurones.

PMID- 7572218
TI  - Villus tip microcirculation in the rat duodenum.
AB  - Duodenal microvascular perfusion was measured in anaesthetized rats both as
      erythrocyte velocity (rcv) in capillaries in the tip of duodenal villi and by
      laser-Doppler flowmetry (LDF). Rcv increased transiently by about 40% during the
      first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid,
      while LDF measurements only showed a transient increase of about 7%, followed by
      a prolonged reduction by about 11%. Since the LDF signal is a measure not only of
      villus microcirculation but also of blood flow in the deeper layers, our results
      may suggest that blood flow is transiently redistributed towards the villi from
      deeper layers. Hypovolaemia (bleeding by approximately 10% of the blood volume)
      reduced rcv in the capillaries by 63% during the first 5 min of hypotension, but
      reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow
      from the tip to deeper layers. The experiments were performed under atmospheric
      oxygen tension, but rcv in the villus capillaries exposed to abdominal PO2
      (approximately 45 mmHg) did not differ significantly from the values obtained
      under the atmospheric oxygen condition, either in the resting situation or during
      hypotension. In conclusion, we have developed an animal model in which red cell
      velocity in the tip of the duodenal villi can be studied for several hours and in
      which alkaline secretion from the duodenum is similar to previously reported
      levels. Our results show that the villus tip microcirculation in the duodenum may
      respond differently from that of deeper layers of the duodenal wall.

PMID- 7572219
TI  - A new method for exchange of perfusion fluid during in vivo micropuncture.
AB  - The first step in the tubuloglomerular feedback (TGF) mechanism is postulated to
      be the sensing of changes in tubular NaCl concentration by the macula densa (MD)
      cells. Despite this, few in vivo studies using different tubular NaCl
      concentrations administered to the MD site have been completed. Methodological
      problems associated with retrograde perfusion might possibly explain this. In the
      present study we present a modification of a method used in in vitro tubular
      perfusion experiments which makes it possible to determine the TGF response using
      retrograde perfusion with a single perfusion pipette. The system is based on the
      use of a fluid exchange pipette introduced through a chamber in the holder of the
      perfusion pipette all the way to the tip of this pipette. The perfusion flow was
      regulated by a pressure head, and by regulating the outflow from the chamber. The
      flow was determined for different tip diameters and for different perfusion
      pressures. Using a tip diameter of 4 microns, the flow through the tip was in the
      range 18-25 nL min-1 at a pressure of 60-70 mmHg. The fluid-exchange pipette was
      tested in vivo by measuring proximal tubular stop-flow pressure while perfusing
      the macula densa region with different NaCl concentration.

PMID- 7572221
TI  - Arachidonic acid transfer across the human red cell membrane by a specific
      transport system.
AB  - The exchange efflux kinetics of [3H]arachidonate at 0 degrees C, pH 7.3 from
      human red cell ghosts to bovine serum albumin (BSA) in buffer is analysed in
      terms of a closed three-compartment model. Using albumin-free ghosts the kinetics
      determines the model parameters: (1) The ratio of arachidonate bound to the inner
      membrane leaflet to that bound to the outer leaflet (B/E), 0.30 +/- 0.03 and (2)
      the rate constant of unidirectional flux through the membrane from B to E (k3),
      0.39 +/- 0.03 s-1. From the model parameter estimates and knowledge of apparent
      equilibrium constants of arachidonate binding to ghost membrane and to albumin,
      we estimate the dissociation rate constant of arachidonate-albumin complex (k1)
      to 0.21 +/- 0.02 s-1. The lowest rate coefficient (delta) of efflux kinetics from
      albumin-filled ghosts decreases by approximately sevenfold over a 10-fold
      increase in intracellular albumin. These delta-values fit fairly well with the
      values predicted by the corresponding model with an unstirred intracellular
      compartment using the parameter values obtained in the studies with ghosts
      without BSA. Model parameters for arachidonate efflux are completely different
      from those obtained for palmitate, suggesting that different transport systems
      determine arachidonate and palmitate membrane transfer. The data show that
      binding to a limited number of specific sites is functioning as the initial and
      obligatory step in the transport. We propose that a protein is directly or
      indirectly controlling the transport capacity.

PMID- 7572220
TI  - Renal and haemodynamic effects of nitric oxide blockade in a Wistar assay rat
      during high pressure cross-circulation of an isolated denervated kidney.
AB  - Blockade of NO synthesis with N-omega-nitro-L-arginine (L-NNA) inhibits the
      vasodepressor response seen in intact Wistar assay rats in which isolated kidneys
      perfused via an extracorporeal circuit are perfused at high pressure. This study
      explores the renal and haemodynamic changes associated with this inhibition.
      Isolated kidneys (IK) were perfused at high pressure (175 mmHg) by a pump in
      series with intact Wistar assay rats in which blood pressure (BP), haemodynamics
      and renal function were studied. Nitric oxide (NO) synthesis was blocked by L-NNA
      (2.5 mg kg-1) in 13 experiments (175NO) while 14 control experiments (175C) were
      performed. IK was perfused at 90 mmHg in seven experiments (90C). The BP drop in
      the 175C assay rat was blocked by L-NNA in 175NO (P < 0.01). However, when the
      blockade was reversed with L-arginine infusion (20 mg kg-1 min-1) BP declined
      also in 175NO. Effective renal plasma flow (ERPF) and glomerular filtration rate
      (GFR) fell dramatically after L-NNA in both the assay rat and in IK despite a
      high perfusion pressure. The marked increase in filtration fraction (FF) after L
      NNA suggests a dominating postglomerular vasoconstriction. The natriuretic
      response in IK to 175 mmHg was also markedly blunted by L-NNA. We conclude that
      NO blockade inhibits the renomedullary depressor mechanism probably by
      restricting renal blood flow, and also blunts the pressure induced natriuretic
      response as a result of a reduced sodium filtration. Finally, the autoregulation
      of whole kidney blood flow seems to be more efficient although set at a higher
      level of vasoconstriction.

PMID- 7572222
TI  - Mitochondrial ATP production rate in 55 to 73-year-old men: effect of endurance
      training.
AB  - The effect of 6-week endurance training on mitochondrial ATP production rate was
      investigated in 14 elderly men. Mean age, body weight and height were 63 +/- 6
      yr, 75.6 +/- 9.2 kg and 174 +/- 4 cm, respectively. Subjects trained on a Monark
      cycle ergometer at 79 +/- 8% of their maximal heart rate for 1 h day-1, 4 days
      week-1. Muscle samples were obtained at rest, before and after endurance
      training, by a needle biopsy technique and used for determination of
      mitochondrial ATP production rate in isolated mitochondria and enzyme assays.
      Endurance training resulted in a significant increase in maximal oxygen uptake (L
      min-1) (P < 0.01). Citrate synthase activity, a mitochondrial marker enzyme, and
      hexokinase activity increased significantly (both P < 0.01) in response to
      training while 3-hydroxyacyl-CoA dehydrogenase and carnitine palmitoyltransferase
      I activities remained statistically unchanged. A higher mitochondrial ATP
      production rate was observed after endurance training with the substrate
      combinations pyruvate+palmitoyl-L-carnitine+L-glutamate+malate (P < 0.01), L
      glutamate (P < 0.001), pyruvate+malate (P < 0.05) and palmitoyl-L
      carnitine+malate (P < 0.01). The largest increase was obtained with L-glutamate
      (170%). Significant correlations were observed between the percent increase in
      citrate synthase activity and those of mitochondrial ATP production rates. It was
      concluded that the increased mitochondrial ATP production rate of aged human
      skeletal muscle with training seems mainly to occur through an increased
      mitochondrial content, and in a way similar to those observed in young men.

PMID- 7572223
TI  - Pronounced plasma fluid loss into dependent regions on standing.

PMID- 7572224
TI  - The effect of change in sympatho-vagal balance on heart rate and blood pressure
      variability in the foetal lamb.
AB  - Cardiac and vascular function is mainly under autonomic nervous control within
      seconds to minutes, although the control is not mature at birth. We studied
      sympathovagal control of heart rate and blood pressure in chronically
      catheterized foetal lambs in the last trimester of gestation. Power spectral
      analysis was used to quantitate the frequency-specific heart rate variability
      (HRV) and blood pressure variability. We performed 15 experiments in seven foetal
      lambs. These preliminary studies showed that parasympathetic blockade by atropine
      (eight experiments) had no significant effect on the distribution of HRV to
      different frequencies. Beta-sympathetic blockade by propranolol (seven
      experiments) decreased the ratio of low and mid to high frequency (0.025-0.13 to
      0.13-1.00 Hz) HRV (P = 0.02). The increased high frequency HRV in the absence of
      a similar increase in blood pressure variability and tracheal pressure
      variability suggests enhanced baroreflex responsiveness after propranolol
      administration. The frequency-specific sympathetic control of HRV in foetal
      lambs, the change in ratio of low and mid to high frequency HRV, might have
      clinical implications in estimating the level of foetal sympathetic activation in
      the follow-up of high-risk pregnancies.

PMID- 7572225
TI  - Nitric oxide regulates coronary blood flow at various coronary arterial pressures
      in intact porcine hearts.
AB  - Nitric oxide (NO) is known to regulate basal coronary blood flow (CBF). The
      objective of the present study was to examine the importance of NO in CBF
      regulation at various coronary arterial pressures (CAPs) in vivo. Experiments
      were performed in 11 open-chest pentobarbitone sodium anesthetized pigs. CAP was
      reduced in steps by a hydraulic occluder on the mid left anterior descending
      coronary artery (LAD) before and after a 5-min intracoronary infusion of the
      inhibitor of NO synthesis, NG-nitro-L-arginine (NOARG, 30 mumol min-1). CAP was
      recorded and NOARG infused through a catheter inserted into the LAD just distal
      to the occluder. CBF was measured by Doppler flowmetry on the LAD. NOARG
      significantly reduced CBF by 11 +/- 4, 20 +/- 5, 10 +/- 3, 15 +/- 4, 19 +/- 2, 25
      +/- 4 and 25 +/- 5 mL min-1 100 g-1 (mean +/- SE) at CAPs of 30 (n = 6), 40 (n =
      9), 50 (n = 9), 60 (n = 9), 70 (n = 9), 80 (n = 8) and 90 (n = 6) mmHg,
      respectively. These decrements were not statistically different, but the
      percentage reductions in CBF after infusion of NOARG were significantly greatest
      at the lowest CAPs. The slight haemodynamic alterations induced by NOARG could
      not explain the reductions in CBF. Thus, the reductions in CBF after infusion of
      NOARG were caused by inhibition of a continuous NO release from the coronary
      endothelium. Coronary NO contributes significantly to CBF at all CAPs between 30
      and 90 mmHg. The pronounced reduction in CBF during NO inhibition at the lower
      CAPs indicates an important vasodilating role of intact endothelium in a region
      supplied by a stenosed coronary artery.

PMID- 7572226
TI  - Energetics of fish larvae, the smallest vertebrates.
AB  - In this review recent findings on the energetics of fish larvae are presented,
      highlighting some of the physiological problems linked to small body size. The
      existence of a mass-independent phase of specific metabolic rate is confirmed but
      it is pointed out that in young fish ontogenetic transitions of metabolic scaling
      have so far been documented only for the routine level of activity. Maximum
      metabolic rate is limited by mitochondrial density in the swimming muscles which
      scales with a mass exponent of approximately 0.9. Mitochondrial density in the
      swimming muscles of a species of fish, from larva to adult, covers about the same
      range as mitochondrial density in the skeletal muscles of mammals. However, the
      aerobic capacity (power density) of mitochondria is one order of magnitude lower
      in fish than in mammals. Energy metabolism in embryos and early larvae of fish is
      almost entirely aerobic. Anaerobic power in the fast muscle fibres is low after
      hatching but increases during the transition from larva to juvenile with a mass
      exponent greater than one. In hypoxic water fish larvae swim more economically
      (i.e. their cost of transport is lower) than in normoxic water. If the rate of
      growth exceeds a critical threshold (about 10% d-1) fish larvae are capable of
      increasing the apparent efficiency of growth, probably by reducing the costs of
      other energy-consuming functions of maintenance.

PMID- 7572227
TI  - Effects of immobilization on the rat soleus muscle in relation to age.
AB  - A hind limb of young adult, adult and old male Wistar rats (4-5, 6-7 and 20-21
      months, respectively) was immobilized for 4 weeks by a plaster cast with the knee
      and ankle joints in a resting position. Enzyme-histochemical, morphometrical and
      contractile characteristics of the soleus muscle were compared with those in age
      matched controls. A pronounced decrease in muscle mass and cross-sectional muscle
      fibre area was found at all ages. The degree of atrophy after immobilization did
      not differ between different fibre types in each age group, but the decrease in
      fibre area was less pronounced in old animals (i.e. the fibre area was decreased
      by 49-64, 53-66 and 27-38% in young adult, adult and old animals, respectively).
      The maximum tetanus force was decreased in all age groups (by 73, 78 and 69% in
      young adult, adult and old rats, respectively) as was the tetanus tension (i.e.
      tetanus force divided by muscle fibre cross-sectional area). The contraction time
      of the isometric twitch was significantly altered, i.e. decreased, only in the
      youngest age group, although it also tended to decrease in old age. A significant
      increase in the number and proportion of fibre types intermediate to types I and
      IIA, was found in the immobilized muscle of 4-5- and 6-7-month-old animals, but
      not in that of old ones (i.e. the proportion of intermediate fibres increased by
      14, 13 and 2% in young adult, adult and old animals, respectively). Thus, in
      contrast to the atrophic changes, the contractile alterations after
      immobilization were not markedly different between young and old age. It is
      further concluded that the age-related fast-to-slow muscle fibre transition that
      occurs in normal soleus during maturation and growth can be partly reversed by
      restrictions of the normal muscle activity and that the ability of the soleus to
      modulate its fibre-type composition in response to a change in activity may be
      diminished in old age.

PMID- 7572228
TI  - Skeletal muscle metabolism during short duration high-intensity exercise:
      influence of creatine supplementation.
AB  - Seven male subjects performed repeated bouts of high-intensity exercise, on a
      cycle ergometer, before and after 6 d of creatine supplementation (20 g Cr H2O
      day-1). The exercise protocol consisted of five 6-s exercise periods performed at
      a fixed exercise intensity, interspersed with 30-s recovery periods (Part I),
      followed (40 s later) by one 10 s exercise period (Part II) where the ability to
      maintain power output was evaluated. Muscle biopsies were taken from m. vastus
      lateralis at rest, and immediately after (i) the fifth 6 s exercise period in
      Part I and (ii) the 10 s exercise period in Part II. In addition, a series of
      counter movement (CMJ) and squat (SJ) jumps were performed before and after the
      administration period. As a result of the creatine supplementation, total muscle
      creatine [creatine (Cr) + phosphocreatine (PCr)] concentration at rest increased
      from (mean +/- SEM) 128.7 (4.3) to 151.5 (5.5) mmol kg-1 dry wt (P < 0.05). This
      was accompanied by a 1.1 (0.5) kg increase in body mass (P < 0.05). After the
      fifth exercise bout in Part I of the exercise protocol, PCr concentration was
      higher [69.7 (2.3) vs. 45.6 (7.5) mmol kg-1 dry wt, P < 0.05], and muscle lactate
      was lower [26.2 (5.5) vs. 44.3 (9.9) mmol kg-1 dry wt, P < 0.05] after vs. before
      supplementation. In Part II, after creatinine supplementation, subjects were
      better able to maintain power output during the 10-s exercise period (P < 0.05).
      There was no change in jump performance as a result of the creatine
      supplementation (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572229
TI  - Protein loss and capillary protein permeability in dependent regions upon quiet
      standing.
AB  - Seven healthy males were exposed to quiet standing (15 min) after supine rest.
      Alterations in the total mass of plasma proteins were analysed from changes in
      plasma volume (PV; determination of control PV and subsequently of induced per
      cent PV changes using Hb/Hct) and protein concentration as revealed in arterial
      blood collected after standing. This approach adopted the concept that valid data
      on overall circulatory haemoconcentrations prevailing on standing can only be
      reached when blood is sampled on resumption of the recumbent posture, whereas
      conventional sampling from the standing subject provides erroneous information.
      The PV reduction on standing averaged 649 +/- 65 mL (16.9 +/- 1.0%). There were
      very similar net decreases in plasma (serum) total protein (7.6 +/- 0.8 g) and
      albumin (7.8 +/- 0.9 g). These findings permitted the following main conclusions
      of physiological and methodological pertinence: (1) Quiet standing leads to a
      clear-cut net decrease in the plasma protein content predominantly confined to
      albumin, in all probability via convection secondary to PV loss by filtration in
      dependent regions. (2) It is suggested that the albumin loss reflects a quite
      high capillary macromolecular permeability in the dependent limbs on standing
      preferentially confined to skin/subcutaneous tissues. (3) The albumin loss
      implies that plasma concentration changes of neither albumin nor of total protein
      can be used to describe the PV loss on standing. However, concentration changes
      of the plasma globulin fraction as a whole, expressed by the difference (total
      protein-albumin), seem to reflect PV alterations approximately.

PMID- 7572231
TI  - The migrating motor complex--the motor component of a cholinergic enteric
      secretomotor programme?
AB  - The role of cholinergic nerves in the cyclic activation of interdigestive
      motility and secretion was studied in 23 healthy volunteers. Net fluid transport
      in a distal duodenal segment and the release of pancreaticobiliary secretions
      into the duodenal lumen, were measured with a triple lumen perfusion technique.
      Interdigestive motor activity was recorded with a low-compliance pneumohydraulic
      system, and the transmural potential difference (PD) was measured as an on-line
      marker of electrogenic anion secretion. Transport parameters were related to the
      migrating motor complex (MMC) in the control situation and after the
      administration of atropine (0.01 mg kg-1 body wt, i.v.). The early part of the
      MMC cycle was characterized by low motor activity, low release of bile and
      pancreatic juice into the duodenal lumen, a slightly lumen positive transmural
      PD, and a non-significant net fluid absorption ('absorptive mode'). Under control
      conditions, motor activity and pancreaticobiliary secretions subsequently
      increased and there was a shift in net fluid transport and transmural PD in the
      secretory direction ('secretory mode'). Furthermore, there was a significant
      correlation between contraction frequency, a more lumen negative PD, and the
      magnitude of net fluid secretion. After the administration of atropine, the
      secretory mode was abolished, but there was still a significant correlation
      between contraction frequency and transmural PD. In conclusion, cholinergic
      neurones seem to mediate the shift from the absorptive to the secretory mode in
      the human distal duodenum. The antisecretory effect of atropine may be the result
      of inhibition of motilin release, reduced activation of tension-sensitive
      intramural secretory pathways, or blockade of cholinergic neurones to the
      secreting epithelium.

PMID- 7572230
TI  - Toxin of the marine alga Prymnesium patelliferum enhances voltage dependent
      Ca(2+)-currents, elevates the cytosolic Ca(2+)-concentration and facilitates
      hormone release in clonal rat pituitary cells.
AB  - The marine flagellate Prymnesium patelliferum produces toxins lethal to fish. The
      toxin extracted from the alga has haemolytic, cytotoxic and neurotoxic effects,
      but the action mechanisms of the toxin are not known in detail. We have examined
      the toxin effects on the voltage sensitive Ca(2+)-currents, the cytosolic Ca(2+)
      level ([Ca2+]i) and the prolactin release in clonal rat anterior pituitary GH4C1
      cells, which possess T- and L-type Ca(2+)-channels. The trans-membrane Ca(2+)
      current was recorded using whole-cell voltage clamp. After 5-15 min exposure to
      the algal toxin at a final concentration of 50,000-100,000 cells mL-1, the Ca(2+)
      currents through both the T- and L-channels showed a 2-3-fold enhancement. The
      voltage sensitivity of the Ca(2+)-currents was not affected by the algal toxin,
      and the toxin-induced currents were inhibited by 100 microM of the Ca(2+)-channel
      blocker D-600. In toxin-exposed cells microfluorometric measurements based on
      fura-2 revealed an increase of [Ca2+]i from 100-150 to 300-500 nM. This elevation
      was delayed and partially inhibited by 100 microM D-600. The algal toxin induced
      prolactin release in a dose-dependent manner, and this effect was inhibited by
      the Ca(2+)-channel blocker verapamil. We therefore conclude that the toxin of P.
      patelliferum affects the Ca2+ homeostasis of the pituitary cells by increasing
      the leak through voltage sensitive Ca(2+)-channels, resulting in increased
      [Ca2+]i and secretion of prolactin.

PMID- 7572232
TI  - Rate of active tension development from rigor in skinned atrial and ventricular
      cardiac fibres from swine following photolytic release of ATP from caged ATP.
AB  - We investigated the rate of tension development (kappa td) after photolytical
      release of ATP from P3-1-(2-nitrophenyl)-ethyladenosine-5'-triphosphate ('caged
      ATP') of atrial and ventricular fibre bundles from pig. Contraction was initiated
      from high-tension (HT) and low-tension (LT) rigor at maximal Ca2+ activation (pCa
      4.5). The kappa td of atrial fibre bundles was 6.8 s-1 from LT and 6.9 s-1 from
      HT rigor. Rate of tension development of ventricular fibre bundles was
      significantly lower (P < 0.001) being 1.06 s-1 and 0.94 s-1 from LT and HT rigor,
      respectively. The kappa td of skinned ventricular fibre bundles incubated in a
      high [K+], low [Ca2+] (cardioplegic) solution prior to the skinning procedure
      decreased significantly (P < 0.05) to 0.73 s-1 and 0.63 s-1 from LT and HT rigor,
      respectively, whereas that of skinned atrial fibre bundles remained at 7.1 s-1
      and 6.9 s-1 from LT and HT rigor, respectively. Phosphorylation levels of the
      myosin light chain 2 isoform in the atrial fibre bundles (ALC-2) was 15.6 +/-
      2.7%. The corresponding values for the two ventricular isoforms, VLC-2 and VLC
      2*, were 31.2 +/- 0.4% and 25.1 +/- 2.1%, respectively. Phosphorylation levels of
      fibre bundles incubated in cardioplegic solution prior to skinning were 11.6%,
      18.9%, and 15.4% of the ALC-2, VLC-2 and VLC-2*, respectively. The results show
      that the rate of tension development is more than seven-fold higher in the atrial
      compared with ventricular fibre bundles. These results correlate with the
      differences in ATPase activity of the contractile proteins in solution and, most
      likely, reflect differences in the myosin isoform composition. In ventricular
      fibre bundles the increased levels of light chain phosphorylation were associated
      with increased rate of contraction.

PMID- 7572233
TI  - Differential actions of exogenous and intracellular spermine on contractile
      activity in smooth muscle of rat portal vein.
AB  - Effects of the naturally occurring polyamine spermine on electrical and
      contractile properties of the rat portal vein were studied. 1 mM spermine nearly
      abolished spike activity and spontaneous contractions and decreased the
      intracellular Ca2+ concentration ([Ca2+]i). The phasic force responses to 0.1 and
      1 microM phenylephrine were partially inhibited, but not the sustain plateau
      contraction caused by 5 microM phenylephrine. The Ca(2+)-force relation in high
      K+ (128 mM)-depolarized veins was shifted to the right, EC50 for Ca2+ increasing
      from 0.50 +/- 0.03 mM (control, n = 8) to 0.65 +/- 0.06 and to 0.94 +/- 0.03 at 1
      (n = 4) and 10 (n = 3) mM spermine, respectively. However, at a Ca2+
      concentration of 2.5 mM, giving maximal force, there was no effect of spermine (1
      mM) on either force or [Ca2+]i. Whereas extracellular spermine thus reduced
      contractile activity at moderate levels of stimulation, increased intracellular
      concentration of spermine potentiated the force response to Ca2+. Intracellular
      loading of spermine by reversible permeabilization increased its concentration by
      2-3 times. The spontaneous activity and response to phenylephrine were unchanged.
      However, the Ca(2+)-force relation of depolarized veins was shifted to the left,
      EC50 decreasing from 0.51 +/- 0.04 mM in controls (n = 7) to 0.36 +/- 0.02 mM in
      the loaded veins (n = 9). Spermine increased Ca(2+)-activated force in portal
      veins permeabilized with beta-escin. The degree of potentiation was consistent
      with observed effects in spermine-loaded intact veins. The results suggest that
      spermine at physiological intracellular concentration may contribute to the
      determination of Ca2+ sensitivity in vascular smooth muscle cells.

PMID- 7572234
TI  - Effect of verapamil on restoration of cardiac performance in raised [K+]o by
      adrenergic stimulation in the rabbit.
AB  - Modulation of the L-type calcium channel by catecholamines improves action
      potential parameters in single ventricular myocytes depolarized by high [K+]o
      Tyrode. Whether this modulation is important in offsetting the negative effects
      of hyperkalaemia in the whole heart is not known. We tested the effects of the
      calcium channel antagonist, verapamil, on restoration of cardiac performance by
      adrenergic stimulation in high [K+]o in anaesthetized rabbits and isolated
      perfused working rabbit hearts. Raised [K+]o decreased SBP, LVP and LVdP/dtmax in
      vivo ([K+]a 8.6 +/- 0.2 mM; n = 10) and aortic flow (AF) in the isolated heart (8
      mM [K+]o Tyrode; n = 25). However, the negative effects of raised [K+]a were
      offset by isoprenaline (Iso, 1 microgram kg-1 min-1 i.v.) in vivo and by
      noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg-1 i.v.; 15
      nM isolated heart) markedly potentiated the negative inotropic effects of raised
      [K+]o in both preparations. Verapamil attenuated the effect of isoprenaline in
      vivo but in the isolated heart, the protective effect of NA in 8 mM [K+] Tyrode
      (AF 97 +/- 10 mL min-1 in 8 mM [K+]o compared with AF 141 +/- 8.5 mL min-1 in 8
      mM [K+]o + NA) was offset by the drug (90 +/- 8 mL min-1 in 8 mM [K+]o + NA + V).
      Furthermore, verapamil abolished aortic flow in 8 mM [K+]o alone. These findings
      suggest that the heart may be critically dependent on modulation of intracellular
      calcium in order to tolerate concentrations of K+ similar to those seen during a
      short burst of intensive exercise ([K+]a 8.6 mM).

PMID- 7572235
TI  - ERG OFF response in frog retina: light adaptation and effect of 2-amino-4
      phosphonobutyrate.
AB  - The intensity-response (V/log I) function of ERG OFF response (d-wave) in dark
      and light adapted superfused frog eyecups was investigated before and after
      blockade of the retinal ON channel by 2-amino-4-phosphonobutyrate (APB). The
      V/log I function of the dark adapted d-wave had two distinct components, each of
      them consisting of an ascendent and descendent part. In eyes adapted to mesopic
      or photopic background the V/log I function had only one component. It was
      shifted to the right along the intensity axis, had a steeper slope and a higher
      maximal response amplitude compared with the two components of the dark-adapted
      V/log I curve. Perfusion with 200 mumol APB markedly increased the d-wave
      amplitude at all stimulus intensities except for the threshold ones in both dark
      and light adapted eyes. The position of the V/log I curve was shifted slightly to
      the left along the intensity axis in dark adapted eyes, but was not changed in
      light adapted eyes. Thus the adaptational mechanism responsible for changes in
      the decremental sensitivity with increased background illumination was not
      altered by APB. The effect of APB was studied also in chromatically adapted eyes,
      in which the responses were predominantly mediated by one photoreceptor type. The
      results showed that the potentiating effect of APB on d-wave did not depend on
      photoreceptor input.

PMID- 7572236
TI  - Efferent renal sympathetic nerve stimulation in vivo. Effects on regional renal
      haemodynamics in the Wistar rat, studied by laser-Doppler technique.
AB  - Intrarenal blood flow regulation probably affects long-term blood pressure
      homeostasis. We have previously shown that 5 Hz renal sympathetic stimulation
      inhibits a humoral renal depressor mechanism, otherwise activated when increasing
      perfusion pressure to an isolated kidney in a cross-circulation set-up. This
      inhibition was suggested to occur as a result of a reduction of renomedullary
      blood flow. Little is known about nervous blood flow regulation within the
      medulla. Therefore in this study, total renal (RBF), cortical (CBF) and papillary
      (PBF) blood flows were separately measured by ultrasonic and laser-Doppler
      techniques in Wistar rats during graded renal sympathetic stimulations. Periods
      of 15 min stimulation at 0.5, 2 and 5 Hz were performed in random order. RBF
      decreased at 0.5 Hz by 1%, at 2 Hz by 16% (P < 0.001) and at 5 Hz by 49% (P <
      0.001). In a similar fashion (r = 0.73, P < 0.001), CBF decreased by 1%, 10% (P <
      0.001) and 37% (P < 0.001), respectively. By contrast, PBF increased by 2% at 0.5
      Hz and 4% at 2 Hz, while it decreased at 5 Hz, by 4% (P < 0.05, compared with 2
      Hz). It seems therefore, that superficial renocortical and total renal blood
      flows are closely regulated by renal sympathetic nerves with increasing
      vasoconstriction at higher frequencies, while medullary blood flow, on the other
      hand, seems to be under strong local control, tending to offset neurogenic flow
      restrictions.

PMID- 7572237
TI  - Prostacyclin aerosol and inhaled nitric oxide fail to reverse pulmonary
      vasoconstriction induced by thromboxane analogue in dogs.
AB  - Inhalation of either prostacyclin (PGI2) as an aerosol or nitric oxide (NO) has
      been shown to elicit selective pulmonary vasodilation during hypoxic pulmonary
      vasoconstriction in dogs. Hypoxia may produce cardiovascular changes confounding
      interpretation of drug effects. Therefore, we investigated the effects of PGI2
      aerosol and inhaled NO (50 p.p.m.) on pulmonary pressure-flow relationships (P/Q
      plots) during thromboxane analogue (U46619) induced pulmonary vasoconstriction.
      In eight anaesthetized dogs infusion of U46619 (0.33 +/- 0.18 micrograms kg-1 min
      1) increased the slope (3.5 +/- 1.1 to 8.4 +/- 1.7 mmHg L-1 min-1, P < 0.001) and
      the intercept (4.4 +/- 2.3 to 10.2 +/- 4.6 mmHg, P < 0.01) of P/Q plots
      indicating pulmonary vasoconstriction. Inhalation of both aerosolized PGI2
      solution (10 micrograms mL-1) and NO (50 p.p.m.) reduced neither the slope nor
      the intercept of the P/Q plots. Increasing the concentration of the aerosolized
      PGI2 solution to 50 micrograms mL-1 (n = 3) did not enhance the effect on
      pulmonary circulation but systemic vascular resistance fell by 23%. Oxygenation
      and intrapulmonary shunt remained unchanged during both PGI2-aerosol and inhaled
      NO. The failure of PGI2-aerosol to induce pulmonary vasodilation indicates that
      during aerosolization PGI2-concentrations at receptor sites on pulmonary vessels
      were insufficient to surmount U46619 induced vasoconstriction; this notion is
      supported by unchanged arterial plasma concentrations of the PGI2 degradation
      product 6-keto-PGF1 alpha. Considering that NO inhaled at comparable
      concentrations in sheep reversed U46619 induced pulmonary vasoconstriction,
      species differences may account for the failure of both PGI2-aerosol and NO to
      dilate pulmonary vessels in dogs.

PMID- 7572238
TI  - Effect of in vivo corticosterone and acute food deprivation on rat resident
      peritoneal cell chemiluminescence after activation ex vivo.
AB  - Adrenoglucocorticoid regulation of rat peritoneal monocyte/macrophage function
      was studied by exposing rats to corticosterone (CS) in the drinking water, and to
      fast (48 h). Production of reactive oxygen metabolites was measured by luminol
      amplified chemiluminescence (CL) in preparations of peritoneal cells activated by
      serum treated zymosan (STZ). Administration of CS which led to an increase in
      plasma CS from 31 (controls) to 46 ng mL-1, reduced CL (per cell) by 31%. Fast,
      which did not change plasma CS or ACTH, also had an inhibitory effect on CL (
      25%), while the combination of CS administration and fast strongly inhibited the
      CL (-89%), indicating that plasma CS and fast reduced CL in a synergistic way.
      Similar effects on cell number were observed: CS-administration, fast and the
      combination reduced macrophage numbers (-13, -19.7 and -55%), while no
      significant effect was observed on the number of monocytes. The effect of
      adrenalectomy (adx) was studied in another series of experiments; adx induced no
      significant change in peritoneal leucocyte number or composition, while cells
      from adx animals had significantly higher chemiluminescence reaction than cells
      from sham operated animals. CS substitution in adx animals reduced CL by 30%
      while sham operated animals had 49% lower CL in adx. The data from adx animals
      also suggest that endogenous levels of CS are inhibitory for CL, but the results
      are not conclusive for the effect of very low doses of CS since other mechanisms
      than elimination of CS could prime the chemiluminescence reaction after adx. In
      conclusion, a moderate elevation of CS after systemic administration in vivo
      reduced the total number of mononuclear phagocytes in rat peritoneum, reduced the
      relative number of macrophages compared with monocytes, and suppressed the
      function of monocytes/macrophages by reducing the production of reactive oxygen
      molecules in activated cells. Furthermore, the effect of corticosterone was also
      dependent on the physiological situation, since the effects of fast and
      corticosterone were synergistic.

PMID- 7572239
TI  - Influence of 12 weeks of hypobaric hypoxia on fibre type composition of the rat
      soleus muscle.

PMID- 7572240
TI  - Evidence of a role for endothelium-derived nitric oxide in the regulation of
      vascular tone during acute haemorrhage.

PMID- 7572242
TI  - Screening for depression in primary care. Development and validation of the
      Depression Scale, a screening instrument for depression.
AB  - Depression is a common mental disorder; effective methods for treating it are
      also available. Its recognition and diagnosis are prerequisite to effective
      treatment. A majority of depressed patients are generally managed in the primary
      care setting; only a half of the cases, however, are identified at their first
      visit. Screening instruments to improve recognition of depression have therefore
      been developed. The Depression Scale (DEPS), consisting of 10 items, was
      developed and tested in primary care patients aged 18 to 64 years. Clinical
      assessments were made on the basis of Present State Examination interviews with
      436 patients. The DEPS proved to be satisfactory. Increasing age and poor
      education had an adverse effect on the screening process, however. The
      sensitivity of the DEPS for clinical depression was 74% and the specificity for
      non-depression 85%. The sensitivity for severe depression was 84% and the
      specificity for symptom-free patients 93%. The DEPS seems to improve the
      recognition of depression in primary care and may also be suitable for screening
      depression in the general population and for identifying high-risk groups.

PMID- 7572241
TI  - Patients dropping out of treatment in Italy.
AB  - The aim of this study was to explore the extent and the specific features of drop
      out for patients having a first contact with an university psychiatric outpatient
      clinic in Italy over the course of 1 year and to determine which variables were
      associated with early termination of treatment. Of the 158 patients selected for
      this study, there was an overall 3-month drop-out rate following the first visit
      of 63%. Of the 59 patients who had returned once after the initial contact, 28
      interrupted subsequently the treatment, although the therapist's plan included
      further visits. The overall drop-out rate at 3 months was thus 82%. The only 2
      variables associated with drop-out rates were the patients' perception of the
      severity of their disorder and the psychiatric history: continuing patients were
      more frequently in agreement with the clinician's judgment as compared with those
      who dropped out and were more likely to have already been in psychiatric
      treatment.

PMID- 7572243
TI  - Genetic factors in early separation anxiety: implications for the genesis of
      adult anxiety disorders.
AB  - An important contemporary conceptualization of anxiety has suggested that
      heightened early separation anxiety is specifically associated with the risk of
      adult panic disorder, with hereditary factors underlying that cluster of anxiety
      disorders. Yet there is a dearth of studies examining whether early separation
      anxiety is inherited. The present twin study, based on a retrospective approach,
      revealed a substantial genetic contribution to separation anxiety in females but
      not in males, with unique environmental influences being important in both gender
      groups. Although speculative, an evolutionary explanation is offered to account
      for the apparent gender difference in the inheritance of early separation
      anxiety. It is hypothesized that, in some women, phylogenetic vestiges of
      separation anxiety may conflict with their need to compete in an individualistic
      manner in the modern workplace. Whether such an attachment-autonomy conflict
      accounts for the increased rate of panic disorder and agoraphobia in women is
      worthy of further study.

PMID- 7572244
TI  - Efficacy of a self-control therapy program in a psychiatric day-treatment center.
AB  - A 12-week self-control therapy program based on the self-control model proposed
      by Rehm was added to the routine program for depressed patients in a psychiatric
      day-treatment center. It was hypothesized that addition of the self-control
      therapy would accelerate the recovery of depressed patients. Twenty-five
      depressed patients were randomly assigned to either standard treatment or
      standard treatment plus the self-control therapy program. At post-test, patients
      in the self-control condition showed significant improvement with regard to self
      control, self-esteem, depression, depressed mood and frequency and potential
      enjoyability of pleasant events, whereas the control patients did not. On 5 of 6
      measures the differences between the groups were significant in the hypothesized
      direction. Although at the 13-week follow-up the positive effects of the self
      control therapy were maintained, between-group differences were no longer
      significant, except for self-control.

PMID- 7572245
TI  - Cost comparison of psychiatric outpatient clinics based in hospitals and in
      primary care (general practice health center).
AB  - The first study to compare the costs of hospital-based and primary care (general
      practice health center)-based psychiatric outpatient clinics is reported. The
      operating costs of both clinic settings were estimated to be similar. There are
      many advantages of primary care-based clinics compared with hospital-based
      clinics. However, as there are no evaluative studies of the comparative efficacy
      of either clinic setting, before policy decisions to encourage primary care
      clinics are made such evaluative studies should take place.

PMID- 7572246
TI  - Neuropsychological deficit in newly diagnosed patients with schizophrenia or
      schizophreniform disorder.
AB  - Forty-six patients with schizophrenia or schizophreniform disorder admitted to
      hospital for the first time were compared with 21 healthy volunteers on
      neuropsychological tests reflecting prefrontal and left respectively right
      hemisphere function. The patients with schizophrenia or schizophreniform disorder
      had a poorer performance on neuropsychological tests (such as Wisconsin Card
      Sorting) compared with healthy volunteers. Both left and right hemisphere seemed
      to be involved. Especially poor performance was found on somewhat complicated
      tests requiring ability of analysis, abstraction and memory, thus indicating
      dysfunction of prefrontal and temporohippocampal regions. Signs of sulcal
      enlargement and size of lateral ventricles on computed tomographic scan
      correlated with poor test performance on some tests both in patients and in
      healthy volunteers. No correlations were found between performance on
      neuropsychological test and negative symptoms.

PMID- 7572247
TI  - Mental symptoms, hostility features and stressful life events in people with
      cancer.
AB  - Hostility features, mental symptoms, and stressful life events were investigated
      in 100 patients (59 men and 41 women) suffering from cancer. Fifty-seven healthy
      men (n = 26) and women (n = 31) were used for comparison purposes. The assessment
      instruments were the Hostility and Direction of Hostility Questionnaire, the
      Delusions Symptoms States Inventory/states of anxiety and depression and a
      modified version of the Schedule of Life Experiences. Women patients reported
      lower scores than healthy women on total hostility, but men patients reported
      higher scores than healthy men. Introverted hostility was increased in both male
      and female patients, but due to different patterns: in women due to lower scores
      on extroverted hostility subscales, especially acting-out hostility, whereas in
      men due to higher scores on introverted hostility subscales, especially guilt.
      Female patients, compared with healthy women, reported significantly higher
      scores on the depressive and anxiety subscales, whereas in the man the
      differences were not statistically significant even though patients reported
      higher scores than normals. On the Schedule of Life Experiences, female patients
      reported statistically significant higher scores than healthy women.

PMID- 7572248
TI  - Seasonal mood variation among Japanese residents of Stockholm.
AB  - Depressive symptoms estimated by the Beck Depression Inventory (BDI) were
      examined in winter and summer in a total of 242 Japanese adults staying less than
      2 years or longer than 10 years in Stockholm, where the length of daylight
      changes dramatically throughout the winter and summer seasons. In spite of the
      difference in the period of residency, both groups of subjects showed more mental
      and somatic depressive symptoms in the winter than in the summer. Moreover, the
      winter BDI score of long stayers was significantly higher than that of short
      stayers. Accordingly, our results suggest that, although seasonal mood variation
      is essentially produced by a chronobiological factor, Swedish lifestyle to which
      long stayers have been accustomed also influences the seasonal mood variation.

PMID- 7572249
TI  - Life satisfaction as a mediator between distressing events and neurotic
      impairment in a general population.
AB  - Quality of life and life satisfaction have often been investigated as concomitant
      variables of anxious and depressive symptoms as well as an outcome measure in
      psychotherapy research. In the present prospective survey, life satisfaction and
      stressful events function as independent variables predicting the development of
      neurotic disturbances in a general population. A random sample of 184 adults
      completed two quality of life surveys (1990 and 1992). Results showed that
      satisfaction in relevant life domains was related to the mental status assessed 2
      years later, and more specifically, that domain satisfactions were mediators of
      the event-impairment relationship. It is argued that life satisfaction might be
      considered as a vulnerability or resistance factor with regard to stress-related
      disorders.

PMID- 7572250
TI  - Classification of psychotic symptoms in dementia sufferers.
AB  - Little attention has been payed to the classification of psychotic symptoms in
      dementia sufferers. This article compares the etiology of delusions, visual
      hallucinations and delusional misidentification and examines the value of factors
      generated from principal components analysis as a possible classificatory system
      in a group of 125 patients with DSM-III-R dementia in contact with clinical
      services who were prospectively evaluated using standardized instruments to
      describe in detail individual psychotic symptoms. The assessment also included
      the Geriatric Mental State Schedule, the History and Aetiology Schedule and the
      CAMCOG. Delusions and visual hallucinations had a distinct cognitive profile as
      did delusions and delusional misidentification, although there was an overlap
      between visual hallucinations and delusional misidentification. Four factors were
      generated from principal components analysis. Three of these closely mirrored the
      3 symptom groups delusions, visual hallucinations and delusional
      misidentification, although the phantom-boarder delusion was correlated with the
      visual hallucination factor and not delusional misidentification. The fourth
      factor included visual hallucinations of relatives and delusions that relatives
      were in the house. This factor was strongly inversely associated with emotional
      distress and could perhaps best be seen as a comfort phenomena. The pattern of
      cognitive deficits and etiological associations of each of the factors were
      independent of one another, supporting the notion that it is useful to consider
      them as separate entities.

PMID- 7572252
TI  - Use and misuse of antidepressant drugs in a random sample of the population of
      Rome, Italy.
AB  - Prescribing patterns of antidepressant drugs were studied, over a period of 30
      months, in a random sample of 8743 residents of the area of Rome, Italy. Data
      from the regional outpatient drug monitoring system were used. The proportion of
      subjects receiving, during the study period, at least one prescription of
      antidepressant drugs, was 5.4%; the female-to-male ratio was 2.1. Consumption
      prevalence increased with age. The single most prescribed drug was fluoxetine
      followed by amitriptyline and ademetionine. For a surprisingly high proportion of
      subjects, the observed length of treatment was shorter than expected on the basis
      of current knowledge in clinical pharmacology. Inappropriate diagnostic and
      therapeutic procedures are likely explanations.

PMID- 7572251
TI  - Lithium prophylaxis of manic-depressive disorder: daily lithium dosing schedule
      versus every second day.
AB  - The prophylactic efficacy of lithium carbonate given every second day versus
      daily intake was compared in a double-blind study including 50 manic-depressive
      patients. The patients met the DSM-III-R criteria for bipolar disorder or
      depressive disorder; according to ICD-8 the patients fulfilled criteria for manic
      depressive disorder: All patients had experienced at least 3 episodes of mania or
      major depression, and all had been euthymic for at least 4 months. The median
      doses of lithium carbonate given were 800 mg/day or 1200 mg/every second day
      corresponding to median 12-h serum lithium concentrations of 0.6 mmol/l or 0.7
      mmol/l, respectively. Manic or depressive relapse was defined as DSM-III-R
      criteria for mania or major depression, and a score > or = 10 on the Bech
      Rafaelsen Mania Scale or the Bech-Rafaelsen Melancholia Scale, respectively. The
      two treatment schedules were allocated at random. Using the Cox proportional
      hazard model for statistical analysis, the lithium dosing schedule of every
      second day did not maintain its prophylactic efficacy against recurrent episodes
      of manic-depressive disorder. The risk of relapse increased 3 times when the
      interval between intake of lithium was extended from 1 to 2 days.

PMID- 7572253
TI  - A study of post-stroke depression in a rehabilitative center.
AB  - This was a prospective study of 52 stroke patients. The incidence of post-stroke
      depression was 55%. A past history of depression was significantly associated
      with the clinical assessment of depression. There was no association between the
      clinical assessment of depression and type and site of lesion and intellectual
      impairment. The clinical assessment of depression was significantly associated
      with the degree of functional impairment. The clinical assessment of depression
      also correlated well with Hamilton Depression Rating Scale score. We conclude
      that post-stroke depression is unlikely to be caused by neuronal injury due to
      the cerebrovascular accident. There is also a significant reactive component to
      it. The Hamilton Depression Rating Scale is suitable for assessing the severity
      of depression in stroke patients.

PMID- 7572254
TI  - Spiritual distress: an indigenous model of nonpsychotic mental illness in primary
      care in Harare, Zimbabwe.
AB  - Spiritual models of illness causation are common in Africa. This article reports
      an investigation of some clinical correlates of patients who believe that their
      problem has a spiritual cause. A cross-sectional survey of random attenders at
      primary health care clinics and traditional medical practitioners (TMP) in Harare
      (n = 302) was performed. Interviews included eliciting of explanatory models,
      indigenous and etic psychiatric measures. Spiritual models of illness were held
      by half the subjects. Patients who hold this model had higher levels of mental
      disorder and were more likely to have a mental illness as judged by the patient,
      care provider and psychiatric measures. The symptoms of such patients resemble
      the construct of anxiety. Such patients are more likely to consult TMP and to
      have a chronic illness. Spiritual models of illness may represent an indigenous
      model to explain the distressing symptoms of nonpsychotic mental illness.
      Including them in training of primary health care providers may improve the
      recognition of mental illness.

PMID- 7572255
TI  - Smooth pursuit eye movements and neuropsychological impairments in schizophrenia.
AB  - Smooth pursuit eye movements (SPEM) and neuropsychological performance were
      examined in a sample of 29 drug-treated schizophrenic patients and 22 healthy
      controls. Patients had impairment in SPEM as well as in a wide range of
      neuropsychological tests (Wechsler Adult Intelligence Scale, Wisconsin Card
      Sorting Test. Finger Tapping, Reaction time, Selective attention, Trail-Making
      and Simultaneous Capacity). Performance indices were more affected than strategy
      executive indices. Drug type (clozapine vs typical) and dose (chlorpromazine
      units) were not related to neuropsychological impairment among the patients.
      Indices from the whole range of tests accurately predicted a subjects' group
      identity (patient vs control). Impaired SPEM was predicted more accurately by
      tests assessing frontal functions. Seven patients, all men, had only marginal
      neuropsychological impairments.

PMID- 7572256
TI  - Are the renal effects of lithium modified by frequency of administration?
AB  - It has been claimed that the unwanted effects and toxicity of lithium can be
      minimized by changes in the dosing schedules. Twenty consecutive psychiatrically
      stable patients were investigated in a cross-over study to determine whether
      renal function and other biochemical tests change significantly with changes from
      once to twice or multiple doses per day or vice versa. There were no significant
      differences between the 3 study conditions on the mood rating scales or a side
      effect scale (UKU). Urine volume, test of renal function and other biochemical
      and hematological indices were similar in all study conditions. We thus conclude
      that dosing strategy does not consistently affect renal function in lithium
      treated patients.

PMID- 7572257
TI  - Adoption as a risk factor for mental disorders.
AB  - Although adoption has been viewed as a risk factor for mental disorders in
      children and adolescents, few studies have investigated this association in
      adults. To address this question, we analyzed data from a random community sample
      of adults where the presence of adoption in the first year of life was
      systematically noted and where the presence of lifetime mental disorders was
      determined by structured interview. In comparison to individuals raised by both
      biological parents, adoption was strongly associated with a history of childhood
      conduct disorder, antisocial personality and drug abuse or dependence. Adoption
      may thus be a risk factor for these mental disorders.

PMID- 7572259
TI  - Improving the usefulness of the Karolinska Psychodynamic Profile in research:
      proposals from a reliability study.
AB  - The interrater reliability of data obtained by use of the Karolinska
      Psychodynamic Profile (KAPP) was tested among 60 women seeking treatment for
      drinking problems. The first rater had a psychodynamic background but was
      minimally trained rating the KAPP subscales and performing KAPP interviews.
      Independent, blind ratings of audiotaped interviews by an experienced KAPP rater
      revealed that 8 of the subscales obtained satisfactory reliability, whereas 6
      subscales showed unsatisfactory reliability. Furthermore, data for one subscale
      (normopathy) showed a zero correlation between raters, probably due to the
      novelty of the construct. Additionally 3 subscales related to bodily aspects were
      of little clinical significance among the present study group. Our data were
      compared with data from previous KAPP reliability studies, and the reasons for
      similarities and discrepancies of results are discussed.

PMID- 7572258
TI  - A double-blind comparison of moclobemide and doxepin in depressed general
      practice patients.
AB  - A total of 56 patients attending a general practitioner for treatment of
      depression, most of whom met the criteria for major depression, were included in
      this double-blind, parallel group, 6-week study, in which the selective MAO-A
      inhibitor moclobemide (MOC; maximum dose 600 mg) was compared with the tricyclic
      antidepressant doxepin (DOX; maximum dose 250 mg). Thirty patients on MOC and 23
      on DOX were assessed after treatment for at least 1 week and are included in the
      response evaluation. Improvement was assessed primarily with the Montgomery
      Asberg Depression Rating Scale (MADRS). There were only 4 drop-outs in the MOC
      group and three in the DOX group after 1 week. Overall improvement measures
      showed a nonsignificant difference in favor of DOX. Two factors were found to
      have prognostic significance: (1) previous or present panic attacks (10 patients
      in the MOC group and--by chance--only one in the DOX group) were associated with
      significantly lower improvement within the MOC group. Since we had no a priori
      hypothesis about this effect, it could be a chance finding. (2) Improvement was
      negatively correlated with age; this was statistically significant in the total
      group as well as in the MOC group, with a nonsignificant trend in the same
      direction in the DOX group. Side effects differed little between the two groups;
      only dryness of mouth appeared with markedly higher frequency in the DOX group.

PMID- 7572260
TI  - Factors predicting readmissions in personality disorders and other nonpsychotic
      illnesses. A retrospective study on 64 first-ever admissions to the Psychiatric
      Clinic of Turku, Finland.
AB  - A retrospective study of factors predicting readmissions and follow-up treatment
      was undertaken of all first-ever episodes of inpatient care (age under 65),
      excluding psychotic and organic mental disorders, during 1987 and 1988 in
      University Psychiatric Clinic in Turku City Hospital, Finland. The cohort
      consisted of 64 subjects, 24 men and 40 women. The study was carried out in the
      end of 1993, thus allowing about 5 years of follow-up. The diagnosis of
      personality disorder did not predict readmission. The only factor predicting
      readmission nearly significantly was not having a relationship. The incidence of
      the revolving door syndrome, defined as 4 or more admissions within 5 years, was
      12.5%. Women had a greater risk of readmission, but not that of the revolving
      door. Patients who had psychotherapy as follow-up treatment showed a frequency of
      8% for 4 or more admissions, whereas patients who had no follow-up treatment had
      a frequency of 21% for 4 or more readmissions. The only factor significantly
      predicting follow-up treatment arrangement was previous treatment contact.

PMID- 7572261
TI  - No association between prenatal exposure to influenza and autism.
AB  - We examined the relationship between the number of autistic patients, obtained
      from the register of the National Autism Society (NAS), born each month between
      January 1953 and December 1988 in England, and the occurrence of influenza
      epidemics one to nine months before birth. The relative risk of developing
      autism, for exposure to influenza during gestation, was assessed by a Poisson
      regression model. Our results indicate that exposure to influenza epidemics
      during gestation is not associated with autism.

PMID- 7572262
TI  - The impact of somatic morbidity on the Hamilton Depression Rating Scale in the
      very old.
AB  - The Hamilton Depression Rating Scale (HDRS) is world-wide the most important
      observer rating scale for depression. Many items of this scale refer to somatic
      symptoms of depression which cast doubt on the validity of HDRS scores in the
      presence of somatic comorbidity as, for example, in elderly patients. The present
      study, therefore, was planned to investigate the validity of the HDRS in cases in
      which the patient is suffering from a depressive illness together with somatic
      illnesses. The study population (n = 516) is a representative sample of citizens
      aged 70 years and older in West Berlin. They were assessed independently by
      internists and psychiatrists. Each positive item of the HDRS scale was then rated
      by the internists as to what degree it reflects somatic morbidity. Results show
      that multimorbidity interferes with the validity of the HDRS. There were 8 items
      for which more than half of all positive scores as rated by psychiatrists were
      seen by the internists as being possibly related to somatic disorders. Patients
      with corrections in the HDRS score showed a somewhat increased rate of medicines
      and cardiovascular diagnoses. There was less ambiguity for items with greater
      severity.

PMID- 7572263
TI  - Temperamental vulnerability in attempted suicide.
AB  - The aim of this study was to explore and describe features of suicidal
      temperament and to describe the psychological domains of vulnerability in
      attempted suicide. Thirty-two suicide attempters were compared with 32 sex- and
      age-matched convalescent surgical controls on self-report personality
      inventories; the Eysenck Personality Questionnaire, the Chapman Scales, the Beck
      Hopelessnes Scale and the Karolinska Scales of Personality. Suicide attempters
      showed higher scale scores on neuroticism, psychoticism, interpersonal
      aversiveness, perceptual aberration, nonconformity, hopelessness, somatic
      anxiety, muscular tension, indirect aggression, suspicion and lower
      socialization. The features of suicidal temperament include hopelessness and
      anhedonia, anxiety, hostility and undirected anger expression, psychosis
      proneness, antisocial traits and interpersonal difficulties. These temperamental
      features might render the suicidal individual particularly vulnerable to suicidal
      behavior.

PMID- 7572264
TI  - Genes and psychosis: old wine in new bottles?
AB  - Despite initial setbacks, linkage studies with DNA markers continue to occupy
      center stage in psychiatric research. Advances in molecular and statistical
      techniques have revived the search for disease genes, leading to a new harvest of
      findings. Most interest in recent years has focused on potential linkages between
      schizophrenia and chromosomes X-Y (the pseudoautosomal region) and 22q12-13.1,
      and between bipolar affective disorder and chromosomes 18 (pericentromeric
      region) and 21q22.3. This article provides a critical evaluation of theses
      studies, with implications for future research. Concerns over earlier linkage
      trials make this scrutiny current and topical.

PMID- 7572265
TI  - Significant reversibility of alcoholic brain shrinkage within 3 weeks of
      abstinence.
AB  - Chronic alcoholism is often associated with brain shrinkage or atrophy. During
      recent years, it has been demonstrated that this shrinkage is, at least in part,
      reversible when abstinence is maintained. There are different hypotheses
      concerning the mechanisms for this reversibility, but many questions are still
      open. Especially the time conditions for these reversible changes are subject of
      discussion. Twenty-eight male patients with severe alcohol dependence were
      investigated in a computed tomographic study at the beginning of abstinence and 3
      weeks later. Planimetric evaluation of 5 selected slices revealed a significant
      decrease in liquor areas and an increase of brain volume. The densitometric
      analysis showed an increase in brain tissue density. In a multiple regression
      approach it was shown that the reversibility was mostly influenced by the age of
      the patients. Our results support neither the hypothesis of an increase in brain
      water as the most important principle for reversibility in alcoholic brain
      shrinkage nor the hypothesis of augmented dendritic growth. Other mechanisms like
      reduced (during chronic intoxication) and normalized (during abstinence) cerebral
      hemoperfusion have to be considered as possible mechanisms for the reversibility
      of alcoholic brain shrinkage.

PMID- 7572266
TI  - Incidence of eating disorders in psychiatric hospitals and wards in Denmark, 1970
      1993.
AB  - Two previous studies in Denmark found diverging results in analyzing trends in
      new cases of eating disorders in the psychiatric in- and day-patient services,
      although the same data source, the nationwide Danish Psychiatric Case Register,
      was used. The present study--also using information from the nationwide Danish
      Psychiatric Case Register, but correcting for several register biases--confirms a
      highly significant increase in new cases of eating disorders in psychiatric
      hospitals and wards. The increase is seen exclusively in younger females. The
      diverging results in the previously mentioned studies in Denmark may be ascribed
      to methodological issues.

PMID- 7572267
TI  - Clinical characteristics of auditory hallucinations.
AB  - We studied 25 clinical characteristics of auditory hallucinations by means of 3
      point observer-rated scales in a sample of 60 inpatients with mainly
      schizophrenic or schizophreniform disorders. The interrater reliability of the
      scales was found to be satisfactory. High levels of conviction about the reality
      of the sensory stimuli, clarity of content, location of their source of origin
      and lack of volitional control were found to be the hallmarks of verbal
      hallucinations. This finding supports the hypothesis that the concept of auditory
      hallucinations represents many aspects of patients' hallucinatory experiences,
      which are relatively independent of one another.

PMID- 7572268
TI  - Time course of visual extrapolation accuracy.
AB  - In two experiments, we examined the extrapolation of a constant-velocity motion
      along a fixed circular path in the frontal plane. A target moved over an arc of
      90 deg and then disappeared. Observers were to assume that the motion continued
      at the original velocity. After a variable time, a line appeared at another point
      on the circle to mark the end of the (invisible) 'motion'. Observers decided
      whether or not the target would have passed this end line, and gave a pass/no
      pass response. In Experiment 1, a time course was established for the observed
      loss in accuracy with increasing duration of invisible motion. Two models of
      accuracy loss were constructed and tested. Both models assume that (1)
      extrapolation is performed by 'tracking' the position of the hidden target, and
      (2) there is no systematic velocity error in tracking, only random variation in
      tracker velocity. Both models predicted changes in hit and false alarm rates
      well, except in a condition where response asymmetries were present. In
      Experiment 2, the hypothesis that observers were tracking the hidden target was
      assessed by presenting a moving distractor during part of the trial. The presence
      of the distractor reduced performance under some conditions, suggesting that
      target tracking was occasionally disrupted. Grossly unequal distributions of
      pass/no-pass responses were observed for the fastest (8 deg/sec) and slowest (4
      deg/sec) target velocities. However, the variable tracker models, using the
      parameter values from the first experiment, made accurate predictions for the 6
      deg/sec condition, in which response distribution was nearly equal. Thus, there
      may be no need to posit systematic velocity error in motion tracking during
      extrapolation. The time course of accuracy decline can be accounted for by random
      variation in tracker velocity when response bias is absent.

PMID- 7572269
TI  - Post-categorical processing and attenuation of the auditory suffix: evidence from
      both immediate and delayed suffixes.
AB  - Recall of the final item in a spoken list is impaired by the presentation of a
      spoken to-be-ignored item following the list. The nature of the processes
      responsible for the stimulus suffix effect (as well as its magnitude) can be
      varied by manipulating the intrinsic characteristics of the relationship between
      the final list (target) item and suffix. A series of experiments show that
      systematic manipulation of both typicality of same-category membership of target
      item and suffix (Experiment 1), and degree of synonymity between target-item and
      suffix (Experiment 2) result in differential attenuation in the magnitude of the
      suffix effect. The effect of the synonymity manipulation persists for up to
      twenty seconds after the presentation of the target-item (Experiment 3). That
      post-categorical processing of the suffix occurs provides direct support for
      semantic coding in short-term memory and contradicts models arguing that short
      term memory is organised according to the principle of physical similarity (e.g.,
      LeCompte and Watkins, 1993).

PMID- 7572270
TI  - Molecular mechanisms and neural pathways mediating the influence of interleukin-1
      on the activity of neuroendocrine CRF motoneurons in the rat.
AB  - The action of immune-system-derived cytokines to stimulate the release of
      corticotropin-releasing factor (CRF) from the hypothalamus and the consequent
      elaboration of ACTH and release of corticosteroids has provided an especially
      useful model to investigate the nature of the intercommunication of
      neuroendocrine and immunological pathways. Substantial evidence exists to support
      the production of cytokines, such as interleukin-1 (IL-1) alpha and beta, within
      the mammalian central nervous system. The mechanisms and neuronal circuitries
      involved in the effects of these cytokines of peripheral and central origin on
      the activity of neuroendocrine CRF motoneurons and the hypothalamic-pituitary
      adrenal axis are described. Also included is a discussion of the influence of IL
      1 on transduction signals controlling the release and the biosynthesis of CRF in
      the parvocellular division of the paraventricular nucleus of the hypothalamus and
      the relationship between these two distinct intracellular processes. The
      relevance of using immediate early genes as indices of neuronal activity in
      immune-challenged rats and the possible roles of c-fos and NGFI-B within
      neuroendocrine CRF motoneurons are outlined. Finally, the effects of acute immune
      response on neuroendocrine functions and brain neuronal activation are presented.

PMID- 7572272
TI  - Regulation and function of central nervous system chemokines.
AB  - In this paper, we discuss the potential involvement of a new family of cytokines,
      termed chemokines, in CNS inflammatory pathology. Chemokines are a family of
      proinflammatory cytokines which are able to stimulate target-cell-specific
      directional migration of leukocytes. Because of this feature, chemokines may be
      potent mediators of inflammatory processes. We have previously reported
      observations indicating that chemokines may be involved in the process of lesion
      formation during autoimmune inflammation within CNS, and, in particular, are
      likely participants in the process of influx of inflammatory cells into the CNS
      parenchyma. We observed also that mechanical injury of brain and subsequent post
      traumatic inflammation may in part be mediated by chemokines. Chemokines
      undoubtedly co-operate with cell-associated adhesion molecules during recruitment
      of leukocytes from blood to CNS. The sequential expression of soluble and
      membrane-bound signals for leukocyte migration is an intricate process that can
      be interrupted by a variety of strategies. Our data suggest that chemokines may
      represent a promising target for future therapy of inflammatory conditions,
      including CNS inflammation resulting from varied insults.

PMID- 7572271
TI  - Neurotrophins and cytokines--intermediaries between the immune and nervous
      systems.
AB  - Neurotrophins (NTs), including nerve growth factor (NGF), are multifunctional: in
      addition to their well-characterized neurotrophic functions they are known to
      regulate and to be regulated by cytokines, components of the immune system. In
      line with this we have found expression of a functional trk proto-oncogene,
      constituting the signal transducing-receptor for NGF, on monocytes/macrophages,
      lymphocytes and basophils. Moreover, NGF synthesis is regulated by a cytokine
      cascade including inflammatory mediators such as interleukin-1 and tumor necrosis
      factor-alpha. The fact that NGF levels are markedly elevated in cerebrospinal
      fluid of patients with multiple sclerosis and in serum of patients with systemic
      lupus erythematosus strongly indicates a role for NGF in immunopathology as well
      as in normal immune function.

PMID- 7572273
TI  - Modulation of interleukin-1 receptors in the neuro-endocrine-immune axis.
AB  - Interleukin-1 (IL-1) receptors with kinetics, pharmacological and biochemical
      characteristics of type I IL-1 receptors have been identified in the mouse neuro
      endocrine-immune axis. In the present study, we examined the in-vitro and in-vivo
      modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of
      AtT-20 mouse pituitary adenoma cells for 24 hr with neuro-endocrine mediators of
      stress such as corticotropin releasing factor (CRF) and catecholamine (beta 2
      adrenergic) receptor agonists produced a dose-dependent increase in cAMP and
      [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone
      significantly inhibited CRF-stimulated cAMP production and decreased both basal
      and CRF-mediated increase of [125I]IL-1 alpha binding. Furthermore, in keeping
      with the effects of stress mediators to upregulate IL-1 receptors in AtT-20
      cells, ether-laparotomy stress in mice resulted in a significant increase in
      [125I]IL-1 alpha binding in the pituitary with no significant alterations
      observed in the brain; in contrast, [125I]oCRF binding in the pituitary was
      significantly decreased after the ether-laparotomy stress. Next, we investigated
      the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following
      endotoxin lipopolysaccharide (LPS) treatment. IL-1 beta levels were dramatically
      increased in the peripheral tissues (pituitary, testis and spleen) at 2-6 hr
      after a single LPS injection (30 micrograms LPS/mouse). However, no significant
      changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha
      binding in the pituitary gland, liver, spleen and testis was significantly
      decreased at 2 hr following a single administration of both low (30 micrograms
      LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1
      alpha binding in the hippocampus was not significantly altered at 2 hr by a low
      dose of LPS and was significantly decreased by high dose administration of LPS
      (300 micrograms/mouse). Following two LPS injections (at 0 and 12 hr), dramatic
      increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen
      and testis were observed at 2 hr after the second LPS injection; a small but
      statistically nonsignificant change was evident in the pituitary. Moreover,
      dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of
      30 micrograms LPS/mouse in both central and peripheral tissues. These data
      provide further support for a role for IL-1 in co-ordinating neuro-endocrine
      immune responses to stress and infection.

PMID- 7572274
TI  - Cytokines in neurodegeneration and repair.
AB  - Cytokines have diverse actions in the brain, some of which may facilitate either
      neurodegeneration or neuroprotection. The expression of cytokines, particularly
      interleukins-1 and -6 (IL-1, IL-6) and tumor necrosis factor alpha, is rapidly
      and markedly induced in response to experimentally induced or clinical
      neurodegeneration. We have demonstrated that central administration of the IL-1
      receptor antagonist (IL-1ra) markedly inhibits neurodegeneration induced by focal
      cerebral ischaemia, local infusion of glutamate receptor agonists or traumatic
      brain injury in the rat. In contrast, IL-1ra offers no protection against
      degeneration of primary cortical neurones in culture caused by exposure to
      agonists of ionotrophic or metabotrophic receptors. In vivo, administration of IL
      1 beta exacerbates ischaemic brain damage, whereas in cell culture, exogenous IL
      1 is neuroprotective at concentrations in the nM range, an effect which appears
      to be mediated by release of endogenous nerve growth factor. Higher
      concentrations of IL-1 (microM range) are neurotoxic to neurones in culture and
      may mimic the involvement of IL-1 in neurodegeneration in vivo. Thus, excessive
      production of cytokines such as IL-1 appears to mediate experimentally induced
      neurodegeneration in vivo, while neuroprotective effects of low concentrations of
      the cytokine suggest a dual role for IL-1 in neuronal survival.

PMID- 7572275
TI  - Interleukin-1 alpha and vasoactive intestinal peptide: enigmatic regulation of
      neuronal survival.
AB  - A neurotrophic role for interleukin-1 alpha (IL-1 alpha) was investigated in
      dissociated spinal cord-dorsal root ganglion cultures. Three observations
      suggested a survival-promoting action for IL-1 alpha in nine-day-old cultures:
      (1) neutralizing antiserum to murine IL-1 alpha decreased neuronal survival; (2)
      treatment with IL-1 alpha in electrically blocked cultures increased neuronal
      survival; and (3) antiserum to the type I IL-1 receptor decreased neuronal
      survival. Treatment with VIP prevented neuronal cell death associated with the
      antiserum to IL-1 alpha. In contrast, treatment of one-month-old cultures with IL
      1 alpha produced neuronal cell death and neutralizing antiserum to the IL-1
      receptor had no effect on neuronal survival in these cultures. These experiments
      suggested that an IL-1-like substance was necessary for neuronal survival during
      a specific stage in development and that a relationship between VIP and IL-1
      alpha might account in part for the neurotrophic properties of VIP. To test if
      VIP might be a secretagogue for IL-1, a neuron-free model system was utilized:
      astroglial cultures derived from cerebral cortex. VIP treatment produced a
      concentration-dependent (EC50: 50 pM) increase in the amount of IL-1 alpha in the
      medium and a decrease in cellular IL-1 alpha. Interleukin-1 beta (IL-1 beta) was
      also increased (EC 50: 1 nM) in the medium by VIP but without depleting IL-1 beta
      in the cytosol. Semi-quantitative measurements of the IL-1 alpha mRNA after VIP
      treatment indicated a significant but transient decrease. These data indicate
      that VIP produced an increase in the secretion of IL-1 alpha while depleting IL-1
      alpha mRNA.

PMID- 7572276
TI  - Differential effects of interleukin-1 beta and interleukin-2 on glia and
      hippocampal neurons in culture.
AB  - The present study was undertaken to assess the effects of interleukin-1 beta (IL
      1 beta) and interleukin-2 (IL-2) on glial and neuronal cells in culture. The
      presence of IL-1 beta-like and IL-2-like immunoreactivity was detected in media
      collected from both astroglial and microglial cultures, indicating that both
      lymphokines can be released from either cell type. However, the levels measured
      in microglial media were significantly higher than in the astroglial media.
      Moreover, the content of IL-1 beta-like immunoreactive material in the media was
      approximately five-to 10-fold greater than that of IL-2, although exposure of
      both microglial and astroglial cultures to IL-1 beta significantly enhanced this
      measure. A possible role for this glial-derived IL-1 beta as an astroglial growth
      factor was substantiated by experiments showing that the lymphokine increased the
      incorporation of [3H]thymidine into astroglial, but not microglial cultures. In
      contrast, IL-2 did not significantly alter glial proliferation. In hippocampal
      neuronal cultures, these lymphokines affected neuronal survival differently.
      Thus, only the highest concentration (500 ng/ml) of IL-1 beta tested decreased
      the long-term (three day), but not the short-term (one day), survival of these
      neurons, whereas neuronal survival was compromised by IL-2 even after short-term
      (one day) exposure. In addition, in the long-term (three-day-old) neuronal
      cultures exposed to IL-2, extensive cellular swelling, vacuolations and neurite
      retractions were noted, even in cultures exposed to relatively low concentrations
      (< 10 ng/ml) of the lymphokine. These effects were not apparent with IL-1 beta or
      the other lymphokines tested, including IL-3, IL-4 and IL-8. The results suggest
      that the glial-derived lymphokines IL-1 beta and IL-2 may have different
      functions in the CNS. Whereas IL-1 beta may have an important role in the
      developing brain as a maintenance and growth-promoting factor, IL-2 may function
      as an inhibitory factor, and may be of significance only in instances during
      which it accumulates in sufficiently high concentrations in the vicinity of
      neurons.

PMID- 7572278
TI  - Neurotrophic effect of hematopoietic cytokines on cholinergic and other neurons
      in vitro.
AB  - We examined the effects of interleukin-3 (IL-3) and other hematopoietic cytokines
      on the neurotransmitters, neurite formation, and differentiation in cholinergic
      and other types of neurons. IL-3, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), macrophage colony-stimulating factor, granulocyte colony
      stimulating factor and erythropoietin (Epo) elevated choline acetyltransferase
      (ChAT) activity in septal cholinergic cell line SN6 as well as in primary
      cultured septal neurons without increasing protein contents of the cells. These
      effects were dose-dependent and the optimal doses were not different from those
      for blood cells. IL-3 had neurite-promoting activity but GM-CSF had no such
      effect. Both IL-3 and GM-CSF decreased intracellular acetylcholine concentration,
      and elevated glutamic acid decarboxylase and intracellular GABA in septal
      neuronal cultures. Epo elevated monoamines in PC12 cells. These effects are
      thought to result from direct action through their specific receptors in neurons,
      because (i) anti-IL-3-receptor antibody abolished the ChAT activity in septal
      neurons increased by IL-3; (ii) mRNA and immunoreactivity for beta subunits of IL
      3 receptors were expressed in septal cholinergic neurons and (iii) presence of
      receptors for GM-CSF and Epo in neurons has been reported. Our observation and
      others strongly support that neural-immune interactions are important not only in
      the defense mechanism in the nervous system but also in the development,
      differentiation and function of neurons.

PMID- 7572277
TI  - Cytokines regulate the cellular phenotype of developing neural lineage species.
AB  - The patterns and mechanisms of action of inductive signals that orchestrate
      neural lineage commitment and differentiation in the mammalian brain are
      incompletely understood. To examine these developmental issues, we have utilized
      several culture systems including conditionally immortalized cell lines,
      subventricular zone progenitor cells and primary neuronal cultures. A neural stem
      and progenitor cell line (MK31) was established from murine embryonic hippocampus
      by retroviral transduction of temperature-sensitive alleles of the simian virus
      40 large tumor antigen. At the non-permissive temperature for antigen expression
      (39 degrees C) in serum-free media, the neural stem cells give rise to a series
      of increasingly mature neuronal progenitor and differentiated cellular forms
      under the influence of a subset of hematolymphopoietic cytokines (interleukins 5,
      7, 9 and 11), when individually co-applied with transforming growth factor alpha,
      after pretreatment with basic fibroblast growth factor. These cellular forms
      elaborated a series of progressively more mature neurofilament proteins, a
      sequential pattern of ligand-gated channels, and inward currents and generation
      of action potentials with mature physiological properties. Because the factors
      regulating the development of central nervous system astrocytes have been so
      difficult to define, we have chosen to focus, in this manuscript, on the
      elaboration of this cell type. At 39 degrees C, application of a subfamily of
      bone morphogenetic proteins of the transforming growth factor beta superfamily of
      growth factors sanctioned the selective expression of astrocytic progenitor cells
      and mature astrocytes, as defined by sequential elaboration of the Yb subunit of
      glutathione-S-transferase and glial fibrillary acidic protein. These lineage
      specific cytokine inductive relationships were verified using subventricular zone
      neural progenitor cells generated by the application of epidermal growth factor,
      alone or in combination with basic fibroblast growth factor, to dissociated
      cellular cultures derived from early embryonic murine brain, a normal non
      transformed developmental population. Finally, application of a different series
      of cytokines from five distinct factor classes (basic fibroblast growth factor,
      platelet-derived growth factor-AA, insulin-like growth factor 1, neurotrophin 3
      and representative gp130 receptor subunit-related ligands) caused the elaboration
      of oligodendroglial progenitor species and post-mitotic oligodendrocytes, defined
      by progressive morphological maturation and the expression of increasingly
      advanced oligodendroglial and oligodendrocyte lineage markers. In addition, seven
      different gp130-associated neuropoietic (ciliary neurotrophic factor, leukemia
      inhibitory factor, oncostatin-M) and hematopoietic (interleukins 6, 11, 12,
      granulocyte-colony stimulating factor) cytokines exhibited differential trophic
      effects on oligodendroglial lineage maturation and factor class
      interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572281
TI  - Neuropathogenic actions of cytokines assessed in transgenic mice.
AB  - Cytokines are potent biological response modifiers that exhibit a spectrum of
      cellular actions. These factors have been implicated as important mediators of
      physiologic and possibly pathophysiologic processes within the CNS. Targeting the
      expression of cytokines to specific tissues in transgenic mice has provided a
      powerful approach to the investigation of complex cellular responses at a
      localized level and also recapitulated more closely the expression of these
      mediators as found in pathogenetic processes. This review will focus on the
      recent application of transgenic technology to achieve the specific cerebral
      expression of cytokines. The targeting of cytokine gene expression to astrocytes
      in transgenic mice has provided new and dramatic insights into the CNS
      pathobiology of these host-response molecules. Specifically: (1) transgenic
      expression of the cytokines IL-6, IL-3 and IFN-alpha in the CNS results in the
      development of acute (high expression) or chronic progressive (low expression)
      CNS disease associated with a spectrum of clinical, physiologic and pathologic
      manifestations; (2) although the clinical, cellular and molecular phenotype
      produced by the cerebral expression of the various cytokines showed some overlap,
      the differences were more prominent reflecting the unique actions of each
      cytokine; (3) these transgenic models which recapitulate many of the structural
      and functional impairments seen in human neurodegenerative diseases, highlight
      the point that cytokines, which normally function as primary regulators of the
      host response, also have the potential to mediate significant injury in the CNS.
      Therefore, these transgenic models have provided a valuable tool for advancing
      our understanding of the CNS pathobiology of cytokines and will no doubt offer a
      unique resource for the development and testing of therapies aimed at abrogating
      the toxic actions of these important mediators.

PMID- 7572280
TI  - Cytokine regulation of astrocyte function: in-vitro studies using cells from the
      human brain.
AB  - Participation of astrocytes in central nervous system pathophysiology is likely
      to involve cytokines, both as stimulators and mediators of astrocyte function. We
      have used highly enriched human astrocyte cultures as an experimental tool to
      investigate the influence of cytokines on adhesion molecule expression and
      synthesis of mediators that are probably important in immune and inflammatory
      reactions involving the nervous system and in cerebral tissue repair. The
      response of astrocytes to interferon-gamma mainly resulted in increased
      expression of major histocompatibility complex antigens and co-stimulatory
      molecules (intercellular adhesion molecule-1, LFA-1 alpha) which mediate
      astrocyte-T-cell interactions. Another co-stimulatory molecule, B7, was neither
      expressed nor inducible by IFN-gamma and other cytokines. TNF-alpha and IL-1 beta
      were more efficient in stimulating synthesis of immunoregulatory and
      proinflammatory cytokines (IL-6, IL-8 and colony-stimulating factors), cytokine
      antagonists (TNF-alpha soluble receptors), or cytokines with a possible
      neuroprotective role (leukemia inhibitory factor); they also increased expression
      of some co-stimulatory molecules (intercellular adhesion molecule-1 and vascular
      cell adhesion molecule-1). Transforming growth factor-beta 1 was a strong inducer
      of leukemia inhibitory factor, but did not affect either major histocompatibility
      complex/co-stimulatory molecule expression or cytokine synthesis. Thus, different
      cytokines activate distinct functional programs in astrocytes, which may play a
      specific role in different brain diseases or at different stages of the same
      disease. It was additionally observed that the response of human astrocytes to
      cytokines (in particular the inducible synthesis of certain cytokines) varied
      greatly depending on the presence or absence of neurons in the culture system.
      This finding suggests that neuronal-glial interactions may be implicated in
      determining the activation threshold of astrocytes to inflammatory cytokines.

PMID- 7572279
TI  - Cytokine network in the central nervous system and its roles in growth and
      differentiation of glial and neuronal cells.
AB  - Cells resident within the central nervous system (CNS) can synthesize, secrete
      and respond to inflammatory cytokines not only contributing to the responses to
      injury or immunological challenge within the CNS, but also regulating their own
      growth and differentiation potential. The actions and cell communication via
      cytokines in the CNS are designated as the CNS cytokine network, in which
      microglia and astrocytes play the central roles. To further characterize the CNS
      cytokine network we investigated the differences in roles of these cells, and
      found that microglia might contribute to the early phase of cytokine production
      reaction and that astrocytes might contribute the late phase of the reaction. We
      also investigated roles of inhibitory cytokines such as TGF beta, IL-4, and IL
      10, and showed that each might play a distinct role in the inhibitory regulation
      in the CNS. We summarized our previous report about cellular distribution of
      cytokine receptors in the CNS cells and discussed their roles in the CNS cytokine
      network. Finally, we investigated that expression of IL-6 and IL-2 receptors in
      neuronal and oligodendrocytic differentiation, respectively. From these results,
      we discussed the features of the CNS cytokine network.

PMID- 7572283
TI  - Neural functions of the transforming growth factors beta.

PMID- 7572282
TI  - The hematopoietic cytokine, colony-stimulating factor 1, is also a growth factor
      in the CNS: congenital absence of CSF-1 in mice results in abnormal microglial
      response and increased neuron vulnerability to injury.
AB  - In this study we used op/op mice, which are deficient in the hematopoietic
      cytokine, colony-stimulating factor 1 (CSF-1), to determine the effect of CSF-1
      on neuronal survival and microglial response in injury. In normal mice microglia
      express the CSF-1 receptor and are primarily regulated by CSF-1, produced mainly
      by astrocytes. The CSF-1 deficiency in op/op mice results in a depletion in the
      number of monocytes and macrophages but does not affect the number or morphology
      of microglia. We produced an ischemic lesion in the cerebral cortex of mice by
      disrupting the pia-arachnoid blood vessels in a defined area. Using Nissl stain
      and astrocyte- and microglia-specific antibodies, we determined the number of
      viable neurons in such injury and the intensity of glial reaction. The cellular
      response to injury on the operated side of op/op mice was compared to that on the
      non-operated contralateral side and to the cellular response in similar lesions
      in CSF-1 producing C3H/HeJ mice. We found that the systemic lack of CSF-1 in
      op/op mice results in a significant increase in neuron vulnerability to ischemic
      injury and considerably reduced microglial response to neuron injury. Remedying
      the CSF-1 deficiency, either by grafting CSF-1 secreting astroglia into the brain
      or by implanting encapsulated CSF-1 secreting fibroblast-like cells into the
      peritoneum, partially restores the microglial response to neuron injury and
      significantly potentiates neuronal survival in cerebral cortex ischemic lesions.
      Astroglial reaction was approximately the same in the lesions in op/op mice,
      grafted and implanted op/op mice and C3H/HeJ mice, indicating that CSF-1
      modulates microglia, but not the response of astrocytes to injury. The degree of
      neuronal survival was not correlated to the degree of microglial proliferation
      and intensity of their reaction. We report some indications that CSF-1, in
      addition to modulation of microglia, may also act directly on neurons.

PMID- 7572284
TI  - Activins as candidate cholinergic differentiation factors in vivo.
AB  - A number of cytokine families have been implicated in shaping neuronal survival,
      growth and gene expression. The neuropoietic and transforming growth factor-beta
      (TGF-beta) cytokines, in particular, have emerged as candidates for regulating
      the phenotype of sympathetic neurons. Culture studies have shown that
      neuropoietic cytokines (such as leukemia inhibitory factor, ciliary neurotrophic
      factor, oncostatin M, growth promoting activity) can induce the cholinergic
      enzyme, choline acetyltransferase (ChAT) and several neuropeptides, whereas
      certain members of the TGF-beta family (activin A, bone morphogenetic proteins-2
      and -6) induce partially overlapping but distinct sets of transmitter and
      neuropeptide genes in sympathetic neurons. Since activins can induce ChAT in
      cultured neurons, we have investigated whether these cytokines are expressed by
      the appropriate cells and tissues to make them candidates for the cholinergic
      differentiation factor that is known to alter the phenotype of sympathetic
      neurons that innervate the sweat gland in the footpad in vivo. In-situ
      hybridization with the anti-sense probe for activin beta B specifically labels
      the sweat glands but not other tissues in the footpads of developing rats.
      Ribonuclease protection assays indicate that beta B as well as the other activin
      and inhibin subunit mRNAs are expressed by a number of tissues, including
      footpad, hairy skin and submaxillary gland. Homogenates of developing rat
      footpads, however, failed to induce the set of neuropeptide genes in cultured
      sympathetic neurons that is characteristic for activins, although neuropoietic
      cytokine activity was readily detectable in this assay. Thus, while activin beta
      B mRNA is expressed in the sweat gland, this tissue does not contain detectable
      activin protein as assayed by its ability to regulate neuronal gene expression.
      Moreover, activin subunit mRNAs are expressed by targets of noradrenergic
      sympathetic neurons in vivo, indicating that activin expression is not limited to
      targets of cholinergic neurons.

PMID- 7572285
TI  - Transforming growth factor-beta 1: a lesion-associated cytokine of the nervous
      system.
AB  - Lesions to the nervous system are nearly universally accompanied by a glial
      response involving both microglia and astrocytes. The growth and immunoregulatory
      cytokine transforming growth factor-beta 1 (TGF-beta 1) has potent effects on
      glial cells in vitro and may play a role in regulating glial activation in vivo.
      Though present only at very low levels in the normal brain, TGF-beta 1 mRNA is
      strongly upregulated in a number of different experimental models suitable to
      study glial responses. Following axotomy of the facial nerve of the rat, about a
      three-fold increase of TGF-beta 1 mRNA in the regenerating nucleus was observed
      with a time-course closely matching that of glial activation. Putative activated
      microglial cells are the major cellular source as revealed by in-situ
      hybridization. TGF-beta 1 was also found to be upregulated around brain tumors,
      in the spinal cord in response to peripheral nerve inflammation and in the
      postischemic hippocampus. In all systems investigated, TGF-beta 1 mRNA could be
      localized predominantly to cells with the typical nuclear morphology of
      microglia. In the peripheral nervous system, nerve transection leads to a massive
      increase in TGF-beta mRNA expression both proximal and distal to the cut site.
      However, whereas TGF-beta 1 mRNA is restricted to the nerve stump in the proximal
      segment, expression is diffuse and widespread throughout the denervated distal
      segment where it was localized mainly to cells with macrophage
      morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572286
TI  - Differential regulation of astrocyte TNF-alpha expression by the cytokines TGF
      beta, IL-6 and IL-10.
AB  - In this study, we demonstrate that transforming growth factor-beta (TGF-beta),
      interleukin-10 (IL-10) and interleukin-6 (IL-6) inhibit tumor necrosis factor
      alpha expression by primary rat astrocytes. Treatment of astrocytes with TGF-beta
      alone had no effect on TNF-alpha expression, however, TGF-beta suppressed
      induction of TNF-alpha expression at both the protein and mRNA level. In
      contrast, IL-10 and IL-6 both inhibited TNF-alpha protein expression by
      astrocytes, but had no effect on mRNA levels. The extent of IL-6-mediated
      inhibition was greatest when astrocytes were pretreated with IL-6 for 12-24 hr,
      then exposed to the inducing stimuli, while IL-10 was an effective inhibitor even
      when added simultaneously with the inducing stimuli. Collectively, these data
      indicate that TGF-beta, IL-6 and IL-10 are all capable of inhibiting TNF-alpha
      expression by astrocytes, although these immunosuppressive cytokines act at
      different levels of gene expression; i.e. TGF-beta at the transcriptional level
      and IL-10/IL-6 at the translational level. These results indicate that TGF-beta,
      IL-6 and IL-10 are important regulators of cytokine production by astrocytes
      under inflammatory conditions in the brain, and can contribute to controlling the
      production of detrimental cytokines such as TNF-alpha.

PMID- 7572287
TI  - Signal transduction pathways in oligodendrocytes: role of tumor necrosis factor
      alpha.
AB  - We have used a combination of electrophysiological and biochemical approaches to
      investigate the effects and the mechanisms of action of tumor necrosis factor
      alpha (TNF-alpha) on cultured oligodendrocytes (OLGs). Our studies have led to
      the following conclusions: (1) prolonged exposure of mature ovine OLGs to TNF
      alpha leads to inhibition of process extension, membrane depolarization and a
      decrease in the amplitudes of both inwardly rectifying and outward K+ currents;
      (2) brief exposure of OLGs to TNF-alpha does not elicit membrane depolarization
      or consistent changes in cytosolic Ca2+ levels; (3) incubation of OLGs with TNF
      alpha for 1 hr results in inhibition of phosphorylation of myelin basic protein
      and 2',3'-cyclic nucleotide phosphohydrolase. Ceramides, which have been shown to
      be effectors of TNF-alpha, are ineffective in inhibiting phosphorylation, whereas
      sphingomyelinase mimics TNF-alpha in this action. These observations suggest that
      other products of sphingomyelin hydrolysis may be the mediator(s) of TNF-alpha
      effect on protein phosphorylation. We have thus demonstrated that TNF-alpha can
      perturb the functions of OLGs via modulation of ion channels and of protein
      phosphorylation without necessarily inducing cell death. It is conceivable that
      modulation of ion channels and protein phosphorylation constitutes effective
      mechanisms for the participation of cytokines in signal transduction during
      myelination, demyelination and remyelination.

PMID- 7572288
TI  - Effect of tumor necrosis factor alpha and beta on human oligodendrocytes and
      neurons in culture.
AB  - Cytokines produced by infiltrating hematogenous cells or by glial cells activated
      during the course of central nervous system disease or trauma are implicated as
      mediators of tissue injury. In this study, we have assessed the extent and
      mechanism of injury of human-derived CNS oligodendrocytes and neurons in vitro
      mediated by the cytokines tumor necrosis factor alpha and beta and compared these
      with the tumor necrosis factor independent effects mediated by activated CD4+ T
      cells. We found that activated CD4+ T-cells, but not tumor necrosis factor alpha
      or beta, could induce significant release of lactate dehydrogenase, a measure of
      cell membrane lysis, from oligodendrocytes within 24 hr. Neither induced DNA
      fragmentation as measured using a fluorescence nick-end labelling technique.
      After a more prolonged time period (96 hr), tumor necrosis factor alpha did
      induce nuclear fragmentation changes in a significant proportion of
      oligodendrocytes without increased lactate dehydrogenase release. The extent of
      DNA fragmentation was comparable to that induced by serum deprivation. Tumor
      necrosis factor beta effects were even more pronounced. In contrast to
      oligodendrocytes, the extent of DNA fragmentation, assessed by propidium iodide
      staining, induced in neurons by tumor necrosis factor alpha was less than that
      induced by serum deprivation. In-situ hybridization studies of human adult glial
      cells in culture indicated that astrocytes, as well as microglia, can express
      tumor necrosis factor alpha mRNA.

PMID- 7572289
TI  - Follow-up of comprehensive geriatric assessment in a family medicine residency
      clinic.
AB  - BACKGROUND: The objective of this study was to evaluate the effect of outpatient
      geriatric consultation by referring academic physicians and to verify the results
      of a previous study. METHODS: We conducted a retrospective review of charts of 37
      patients referred for geriatric consultation during a 7-month period of a
      university- and community-hospital-affiliated family practice residency clinic in
      urban northeast Washington, DC. The consultation involved team assessment, which
      led to formal recommendations to the attending physician. Main outcome measures
      included total number and category of recommendations made, as well as a total
      number and category of recommendations adhered to by referring physicians.
      RESULTS: There were 29 women and 8 men with an average age of 79.1 years; 5 were
      white and 32 were African-American. For the 23 patients for whom follow-up could
      be determined, the mean number of total diagnoses per patient was 11.4 (SD 3.5).
      The mean total number of recommendations made per patient was 18.1 (SD 5.9). The
      mean total number of recommendations acted upon per patient by referring
      physicians was 9.5 (SD 4.4). The recommendations fell into the following
      categories: rehabilitative 64 percent, radiologic 57.1 percent, laboratory 56.9
      percent, total medication 55.6 percent, medical 50 percent, health maintenance
      47.1 percent, social service 46.2 percent, sensory 33 percent, other 28.6
      percent, educational 20 percent, and nutritional 14.3 percent. CONCLUSIONS:
      Multidisciplinary geriatric assessment in an academic outpatient setting provides
      a comprehensive assessment for faculty and resident physicians in training.
      Recommendations will be adhered to only 50 to 70 percent of the time, possibly
      because of the demographic and socioeconomic mix and overall health of the
      patient population, health care priorities of the referring physician, and costs
      and availability of various interventions. Physicians in training should be
      exposed through continuing medical education to various aspects of geriatric
      assessment.

PMID- 7572290
TI  - Knowledge and attitudes of Minnesota primary care physicians about barriers to
      measles and pertussis immunization.
AB  - BACKGROUND: Understanding the causes of low levels of childhood immunization is
      critical to preventing outbreaks of vaccine-preventable diseases. Hence, we
      examined physicians' knowledge and attitudes about measles and pertussis vaccines
      and barriers to immunization. METHODS: We developed a telephone questionnaire,
      subjected it to a pilot test, and subsequently interviewed Minnesota
      pediatricians, general practitioners, rural family physicians, and urban family
      physicians. The physicians were selected by a random process. RESULTS: The
      response rate was 76.4 percent (411 of 538 eligible physicians). Almost all
      physicians thought that vaccine efficacy was high and that the likelihood of
      serious side effects was low. Respondents were divided, however, about the
      likelihood of serious complications from pertussis disease and the role of adults
      as a pertussis reservoir. Many physicians inappropriately believed certain
      conditions were contraindications to vaccination; for instance, 33 percent of
      physicians would not administer measles, mumps, and rubella vaccine to a child
      whose mother was pregnant. Many physicians (31 percent) would not administer four
      vaccines simultaneously because of concerns that included parental acceptance and
      vaccine efficacy. Physicians were more likely to refer children without insurance
      (P < 0.001) or with Medicaid (P < 0.001) than children with insurance to health
      department vaccine clinics for immunization. CONCLUSIONS: For immunization rates
      to reach high levels, changes are needed in health care system issues, such as
      vaccine reimbursement, and in provider practices, such as interpretation of
      vaccine contraindications.

PMID- 7572291
TI  - An analysis of 190 cases of suspected pesticide illness.
AB  - BACKGROUND: The diagnosis of mild to moderate pesticide exposure presents a
      challenge because the signs and symptoms of exposure are similar to those of many
      other diseases. We reviewed all alleged pesticide injuries seen in a single
      office during a 6-year period to determine which findings were useful in
      discriminating between a pesticide-related illness and other causes. METHODS: We
      reviewed retrospectively the charts of 190 patients alleging pesticide illness
      who were treated in a standardized manner. RESULTS: One hundred sixteen (116)
      patients (61.1 percent) were found to have pesticide illness. Important
      predictors of pesticide illness were anxiety, vertigo, nausea, vomiting, tearing,
      and weakness. Seventy-four patients (38.9 percent) were found to have
      nonpesticide-related illness, with nonspecific irritant contact dermatitis and
      scabies the most common diagnoses. Rash was the only significant predictor of
      nonpesticide related illness. CONCLUSIONS: It is difficult to relate signs and
      symptoms to pesticide poisoning, and exposure history is very important.
      Alternative diagnoses need to be considered. Laboratory tests are not nearly as
      valuable as many might expect, and skin rash is not a common finding in mild to
      moderate pesticide poisoning.

PMID- 7572292
TI  - Evolution of a successful community bicycle helmet campaign.
AB  - BACKGROUND: Bicycling injuries claim more than 900 lives each year in the United
      States, and the major cause of deaths is head injuries. Bicycle helmets can
      prevent head and brain injuries, yet helmet use rate remains low. Helmets are
      expensive, and their cost can be prohibitive. This study asks the question, "If
      bicycle helmets are made affordable, will they be worn?" METHODS: A multifaceted
      bicycle helmet campaign was begun in Grand Junction, Colorado, population 76,000,
      in 1992 and was evaluated after its first 2 years. The educational component
      involved presentations in local schools and at community functions, physician
      education, and media promotions. A discount helmet program was established
      through community donations, which allowed helmets to be sold to low-income
      families for $5 and to middle- and upper-income families for $15; approximately
      2400 helmets were sold. One year later a local retailer sold helmets for $12.99;
      approximately 4000 helmets were sold. RESULTS: Twenty-three locations were
      surveyed in 3 consecutive years by observers looking for bicycle riders and the
      presence or absence of helmets. The base-line overall use rate in 1992 was 9.9
      percent, which increased to 20.9 percent in 1993 and to 37.1 percent in 1994.
      There were increases in helmet use in all age groups. CONCLUSIONS: A community
      bicycle helmet campaign that combines affordable helmets with appropriate
      education can effect an increase in helmet use. A major key to a successful
      program is a local retailer willing to sacrifice profits to promote helmet sales
      and use.

PMID- 7572293
TI  - Spider bites.
AB  - BACKGROUND: This review provides the physician with a clinical approach to the
      diagnosis and management of spider bites. It examines the recent literature
      concerning management of bites causing dermonecrosis, secondary infection,
      neuromuscular damage, and allergic reactions. METHODS: Using the key words
      "spider bites," "brown recluse spider bites," "necrotic arachnidism," "black
      widow spider bites," "latrodectism," and "Tegenaria agrestis (Hobo spider)," the
      MEDLINE files were researched for articles pertinent to the practicing physician.
      Texts related to spiders and spider bites were also consulted. RESULTS AND
      CONCLUSIONS: At least 60 species of spiders have been implicated in human bites.
      Most cause bites of minimal medical importance, requiring little treatment. Some
      (brown recluse, Hobo spider) cause severe cutaneous and systemic reactions
      requiring intensive medical management. The black widow bite can cause severe
      neurologic problems requiring the use of antivenin. Spider bites are frequently
      difficult to diagnose because the spider is not seen at the time of the suspected
      bite. Such bites should be labeled arthropod bites, vector unknown.

PMID- 7572295
TI  - Occupational medicine content of Oregon family physician practices.
AB  - BACKGROUND: Little has been published in the medical literature about the
      occupational medicine content of family practice. Little is known about the
      educational interventions needed for family physicians to improve the care they
      provide to patients suffering from occupational-related disorders. METHODS: A
      questionnaire based on a curriculum in occupational medicine proposed by a
      subcommittee of the Education Committee of the American Academy of Family
      Physicians for the guidance of family practice residency directors was sent to a
      random sample of 100 Oregon family physicians from a total of approximately 570
      active practicing members of the Oregon Academy of Family Physicians. Ninety
      three completed questionnaires were returned. RESULTS: Occupational medicine
      constituted a significant part (14 percent) of the practices of Oregon family
      physicians. The respondents rated management of chronic disability, disability
      determination, repetitive trauma disorders, and legal issues as the most
      important occupational medicine problems in their practices. These issues were
      also those about which they thought they needed additional training. CONCLUSIONS:
      Education in occupational medicine for family physicians must be better tailored
      to fit their needs and their priorities. The responses to this survey of
      practicing family physicians in Oregon suggest that more training in the areas of
      chronic disability management, disability determination, the management of
      repetitive trauma disorders, and legal aspects of occupational disorders is
      needed.

PMID- 7572294
TI  - Renovascular hypertension: a noninvasive screening approach using captopril
      renography.
AB  - BACKGROUND: Noninvasive cost-effective screening of hypertensive patients for
      renovascular hypertension is a desirable approach to a rare disorder. Currently
      many patients are screened with angiography, which is both invasive and
      expensive. METHODS: A MEDLINE search from 1985 through July 1994 using the key
      words "renovascular hypertension," "noninvasive," "screening" generated 16
      references. We reviewed these references, as well as several additional
      references, in an effort to find a reliable noninvasive screening test for
      renovascular hypertension. RESULTS AND CONCLUSIONS: To date, the most reliable
      noninvasive screening test for renovascular hypertension is captopril renography.
      Results of captopril renography allow the physician to diagnose renovascular
      hypertension with an accuracy of greater than 90 percent. Cost-effectiveness
      requires appropriate selection of high-risk hypertensive patients for subsequent
      investigation with captopril renography. Hypertensive patients who have
      fibromuscular dysplasia, which is most commonly found in young white women, have
      the best treatment outcomes.

PMID- 7572296
TI  - Otitis media with effusion in young children: treatment in search of a problem?
      Agency for Health Care and Policy Research.

PMID- 7572297
TI  - Depression during hormonal treatment of prostate cancer.

PMID- 7572298
TI  - Pinworms in pregnancy.

PMID- 7572299
TI  - Shy-Drager syndrome: recognition and management.

PMID- 7572300
TI  - Cervical cord compression in diffuse idiopathic skeletal hyperostosis.

PMID- 7572301
TI  - Rhett Butler and the superior physician.

PMID- 7572302
TI  - Comprehensive geriatric assessment: is it too comprehensive for compliance and
      cost-effectiveness?

PMID- 7572303
TI  - Juvenile rheumatoid arthritis.

PMID- 7572304
TI  - Fever in infants and children.

PMID- 7572305
TI  - The effects of menopause and age on calcitropic hormones: a cross-sectional study
      of 655 healthy women aged 35 to 90.
AB  - Although women lose 30% of their skeletal mass after the menopause, the mechanism
      of this loss is uncertain. Clearly estrogen deficiency is important but whether
      this works only through direct effects on the skeleton is uncertain. To examine
      these mechanisms further we have evaluated calcium-related metabolic factors in
      655 healthy women. Fasting blood samples were collected from all subjects who
      were up to 35 years past the menopause, and fasting urine and 24-h urine samples
      were collected in 365 women who were up to 25 years past the menopause. In the
      first 15 years postmenopause, there was a rise in total plasma calcium due to a
      rise in albumin. Bone resorption (hydroxyproline creatinine ratio), bone
      formation (alkaline phosphatase), and the urine calcium creatinine ratio all rose
      at menopause and remained elevated for the next 25 years. There was a transient
      further rise in bone resorption for the 10 years following menopause. Neither PTH
      nor the free calcitriol index changed for the first 10 years following menopause.
      Ten years past the menopause, although total calcitriol rose, the free calcitriol
      index fell due to a rise in vitamin D binding protein. PTH began to rise at 15
      years past menopause. GFR fell gradually over the 25 years following menopause.
      Thus following menopause there is an increase in bone turnover and increased
      urine calcium loss independent of any effect of PTH or calcitriol, suggesting a
      direct effect of estrogen deficiency on bone and kidney.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7572306
TI  - The skeletal effects of spaceflight in growing rats: tissue-specific alterations
      in mRNA levels for TGF-beta.
AB  - Dynamic weight bearing is important for normal growth and maintenance of the
      skeleton in humans and laboratory animals. Transforming growth factor-beta (TGF
      beta) has been implicated as having autocrine and paracrine actions in bone. The
      purpose of this study was to examine mRNA levels of TGF-beta in skeletal tissues
      of growing male rats following skeletal unweighting during an 11-day spaceflight.
      Animals were sacrificed 5-8 h after the skeleton was reloaded. Spaceflight
      resulted in decreases in cortical bone area and periosteal bone formation, but no
      change in medullary area and endocortical bone formation. In addition,
      spaceflight had no effect on longitudinal bone growth. TGF-beta was reduced
      relative to the ground controls in the hindlimb periosteum, but was not
      significantly altered in the growth zone of the tibial metaphysis. Similarly,
      mRNA levels for type I collagen were reduced in the periosteum, but not in the
      metaphysis of flight animals. The results suggest a potential role of TGF-beta as
      an intermediate in the signal transduction pathway for mechanical loading.
      Further, they indicate skeletal tissue compartment-dependent changes in mRNA
      levels for TGF-beta following weightlessness.

PMID- 7572307
TI  - Carboxy-terminal propeptide of human type I collagen and pyridinium cross-links
      as markers of bone growth in infants 1 to 18 months of age.
AB  - Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations,
      as a marker for bone formation, and urinary pyridinium (Pyd) cross-link
      concentrations, as a marker of bone resorption, were determined in 66 healthy
      infants aged 1-18 months who are being studied longitudinally. We hypothesized
      that there would be a positive correlation of growth velocity, increase in bone
      area, and bone mass accretion rates with PICP and Pyd cross-link concentrations.
      Since osteocalcin is currently used as a marker of bone formation, serum
      osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd
      cross-link concentrations were significantly greater than adult concentrations.
      Future growth velocity, increase in bone area, and bone mass accretion rates were
      not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth
      velocity during the 3 months preceding sample collection correlated with serum
      PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p < 0.001; r = 0.379, p
      < 0.001; and r = 0.516, p < 0.001, respectively). Previous increase in bone area
      correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship
      between the infant's previous bone mass accretion rate and PICP was of borderline
      significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd
      cross-link concentrations, and parameters of bone growth are provided for infants
      1-18 months of age and indicate that these markers reflect past and current bone
      metabolism and may be helpful in monitoring bone disorders in infants.

PMID- 7572308
TI  - Evidence that human bone cells in culture secrete insulin-like growth factor
      (IGF)-II and IGF binding protein-3 but not acid-labile subunit both under basal
      and regulated conditions.
AB  - Insulin-like growth factors (IGFs) are found in human circulation predominantly
      as part of a growth hormone (GH)-dependent complex of 125-150 kD, which is
      composed of three subunits: IGF-I or IGF-II, an acid stable IGF binding protein
      (IGFBP)-3, and an acid labile subunit (ALS). Although recent studies demonstrate
      that a number of cell types in culture secrete IGFs and IGFBP-3, very little is
      known with regard to the origin of circulating ALS. To test the hypothesis that
      human bone cells (HBCs), which produce abundant amounts of IGF-II and IGFBP-3,
      also produce ALS, we measured the IGF-I, IGF-II, IGFBP-3, and ALS levels using
      specific radioimmunoassays (RIAs) in the conditioned medium (CM) of untransformed
      normal HBCs and SaOS-2 osteosarcoma cells treated with various effectors (IGF-II,
      osteogenic protein-1 [OP-1, bone morphogenetic protein-7] and human GH) for 48 h.
      No detectable levels (< 3 ng/ml) of ALS were found in the CM of various HBC types
      under basal conditions. In contrast, CM collected from liver explants in culture
      contained significant amount of ALS prepared and assayed under identical
      conditions. The IGF-I level was also undetectable in the CM of various HBC types.
      In the IGF-II (3, 30 ng/ml)-treated HBC CM, the IGFBP-3 level was increased in a
      dose-dependent manner but neither IGF-I nor ALS could be detected. In the SaOS-2
      cell culture, OP-1 (1, 100 ng/ml) increased both IGF-II and IGFBP-3 secretion but
      neither ALS nor IGF-I secretion. Treatment of HBCs with GH (1, 10, 100 ng/ml) had
      no significant effect on the secretion of either IGF-I, IGF-II, IGFBP-3, or
      ALS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572309
TI  - A study of the relationship between mineral content and mechanical properties of
      turkey gastrocnemius tendon.
AB  - The vertebrate skeletal system undergoes adaptation in response to external
      forces, but the relation between the skeletal changes and such forces is not
      understood. In this context, the variation in the amount and location of
      calcification has been compared with changes in mechanical properties of the
      normally mineralizing turkey gastrocnemius tendon using ash weight measurements,
      X-ray radiography, and mechanical testing. Radiographic evidence from 12- to 17
      week-old birds showed calcification in only portions of gastrocnemius tendons
      proximal to the tarsometatarsal joint. Mechanical testing of these dissected
      proximal regions demonstrated an increased ultimate stress and modulus and a
      decreased maximum strain that appeared to parallel calcification. Further, stress
      strain curves of portions of uncalcified turkey gastrocnemius tendon were shaped
      similar to those of other typical unmineralized tendon curves while highly
      calcified tendons yielded curves resembling those of bone. The proximal portions
      of the gastrocnemius where mineralization begins were observed to have a
      decreased tendon cross-sectional area compared with distal portions which do not
      mineralize. Based on the resultant measures of mineral content and location and
      mechanical properties, it is hypothesized that increased calcification is a
      result of increased stresses at certain locations of the tendon, perhaps the
      consequence of the natural forces exerted by the large leg muscles of the bird
      into which the gastrocnemius inserts. More specifically, tendon calcification may
      be the result of stress-induced exposure of charged sites on the surfaces of
      collagen molecules, fibrils, or fibers so that deposition of mineral and
      subsequent mechanical reinforcement occur in the tissue.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7572310
TI  - Impact of soft tissue on in vivo accuracy of bone mineral measurements in the
      spine, hip, and forearm: a human cadaver study.
AB  - The impact of soft tissue in vivo on accuracy of bone mineral density (BMD)
      measurements of the spine and hip by dual energy X-ray absorptiometry and of the
      forearm by single photon absorptiometry was assessed by use of 14 human cadavers.
      The in vivo accuracy errors (SEE%) were: forearm 3-5%, anteroposterior spine
      5.3%, lateral spine 10-12%, and femoral greater trochanter, neck, total,
      intertrochanteric, and Ward's triangle 3%, 6.5%, 6.7%, 8%, and 11-13%,
      respectively. Except from the lateral spine and the greater trochanter, the
      slopes of the linear regressions of in vivo BMD against in vitro BMD were not
      significantly different from 1 (p > 0.05). The calculated random accuracy error
      of BMD measurements due to fat inhomogeneity was estimated to 3-4% for the
      anteroposterior spine and 9-14% for the lateral spine (from abdominal computed
      tomography in 26 healthy women). In conclusion, acceptable accuracy errors below
      6-7% (of soft tissue in vivo) of BMD measurements were obtained in the
      anteroposterior spine, the forearm, and the neck, greater trochanter, and total
      proximal femur.

PMID- 7572311
TI  - Effects of methotrexate on human osteoblasts in vitro: modulation by 1,25
      dihydroxyvitamin D3.
AB  - This study was designed to investigate whether methotrexate (MTX), used in the
      treatment of rheumatoid arthritis (RA), affects proliferation and differentiation
      of human osteoblasts in culture. The effects of MTX were assessed by analyzing
      markers of proliferation and differentiation of human trabecular bone-derived
      osteoblast-like cells cultured in the presence or absence of 1,25
      dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX
      resulted in a strong dose-dependent inhibition of cell proliferation with half
      maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline
      phosphatase (AP) activity, the number of cells expressing cytochemical AP, or
      basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an
      enhanced AP expression and osteocalcin production coinciding with a decreased
      osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses > or =
      100 nM further inhibited osteoblast growth and induced a significant stimulation
      of AP expression and activity, and production of osteocalcin above the values
      reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent
      inhibitor of osteoblast proliferation but did not affect basal osteoblastic
      phenotypic expression. In the presence of the osteoblast differentiation
      promoter, 1,25(OH)2D3, MTX further inhibited cell growth which was associated
      with enhanced AP activity and osteocalcin production. Thus, MTX may have profound
      effects on bone metabolism and remodeling by interfering with bone cell turnover.

PMID- 7572314
TI  - A comparison of the effects of parathyroid hormone and parathyroid hormone
      related protein on osteocalcin in the rat.
AB  - We compared the effects of parathyroid hormone (PTH1-34) and parathyroid hormone
      related protein (PTHrp1-34) on osteocalcin release in the isolated rat hindlimb
      and in intact and thyroparathyroidectomized (TPTX) rats. PTH1-34 suppressed
      osteocalcin release from perfused rat hindquarters, while PTHrp1-34 had no effect
      on osteocalcin release, despite comparable stimulation of cAMP production.
      Similarly, serum osteocalcin declined in the intact and TPTX animals by 5 h after
      a single dose of PTH1-34, while there was no response to PTHrp1-34. Chronic
      administration of PTH1-34 or PTHrp1-34 produced comparable hypercalcemia and
      hypophosphatemia in sham-operated and TPTX animals. Chronic PTH1-34
      administration produced significant increases in serum osteocalcin both in the
      sham-operated rats and in the TPTX animals. However, in animals chronically
      treated with PTHrp1-34, there was no change at any time point in osteocalcin in
      either sham-operated or TPTX rats. These differences could be inherent or merely
      due to potency differences between the two peptides.

PMID- 7572312
TI  - Cell-to-cell communication in osteoblastic networks: cell line-dependent hormonal
      regulation of gap junction function.
AB  - We have characterized the distribution, expression, and hormonal regulation of
      gap junctions in primary cultures of rat osteoblast-like cells (ROBs), and three
      osteosarcoma cell lines, ROS 17/2.8, UMR-106, and SAOS-2, and a continuous
      osteoblastic cell line, MC3T3-E1. All cell lines we examined were functionally
      coupled. ROS 17/2.8 were the more strongly coupled, while ROB and MC3T3-E1 were
      moderately coupled and UMR-106 and SAOS-2 were weakly coupled. Exposure to
      parathyroid hormone (PTH) for 1 h increased functional coupling in ROB cells in a
      concentration-dependent manner. Furthermore, PTH(3-34), an analog of PTH with
      binds to the PTH receptor and thus attenuates PTH-stimulated cAMP accumulation,
      also attenuated PTH-stimulated functional coupling in ROB. This suggests that PTH
      increases functional coupling partly through a cAMP-dependent mechanism. A 1 h
      exposure to PTH did not affect coupling in ROS 17/2.8, UMR-106, MC3T3-E1, or SAOS
      2. To examine whether connexin43 (Cx43), a specific gap junction protein, is
      present in functionally coupled osteoblastic cells, we characterized Cx43
      distribution and expression. Indirect immunofluorescence with antibodies to Cx43
      revealed that ROS 17/2.8, ROB, and to a lesser extent MC3T3-E1 and UMR-106,
      expressed Cx43 immunoreactivity. SAOS-2 showed little if any Cx43
      immunoreactivity. Cx43 mRNA and Cx43 protein were detected by Northern blot
      analysis and immunoblot analysis, respectively, in all cell lines examined,
      including SAOS-2. Our findings suggest that acute exposure to PTH regulates gap
      junction coupling, in a cell-line dependent manner, in osteoblastic
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572313
TI  - Comparison of methods for defining prevalent vertebral deformities: the Study of
      Osteoporotic Fractures.
AB  - Women with vertebral deformities caused by osteoporosis have more back pain and
      disability and are at higher risk for subsequent vertebral deformities than women
      without deformities. Despite the importance of vertebral deformities, there has
      been a great deal of controversy about how to identify or define them. In order
      to compare methods for defining vertebral deformities, we studied spinal
      radiographs from women in the Study of Osteoporotic Fractures (SOF), a cohort
      study of 9704 non-black women over age 65 recruited from population-based
      listings in four clinical centers. Using radiographs obtained at the baseline
      exam, we compared five methods for defining vertebral deformities: one based on a
      semiquantitative reading by a radiologist and four using vertebral morphometry.
      The semiquantitative method was compared with the other methods in a random
      sample of 503 films, while the morphometric methods were compared with each other
      in a larger sample of 9575 films. We tested a system of "triage" in which only
      those films with evidence of deformity were assessed by morphometry. We compared
      the relationship between deformity, defined by each method, and a variety of
      clinical criteria including bone mineral density at the lumbar spine, height loss
      since age 25, back pain, and incidence of subsequent deformity. Semiquantitative
      reading and three of the four morphometry-based methods provided similar
      relationships to clinical criteria. The fourth morphometry method (based on
      ratios of each vertebral height to the corresponding height at T4) produced
      significantly weaker relationships for several of the clinical validation
      criteria. Triage of radiographs rarely resulted in missed deformities and did not
      reduce the performance of any of the methods. We conclude that use of any of the
      similar methods, with or without triage, provides a valid approach to defining
      vertebral deformities.

PMID- 7572315
TI  - Effects of the bisphosphonate YM175 on bone mineral density, strength, structure,
      and turnover in ovariectomized beagles on concomitant dietary calcium
      restriction.
AB  - We evaluated the effect of YM175 on bone in ovariectomized beagles fed a calcium
      restricted diet for 18 months. Groups 1 (n = 6) and 2 (n = 6) underwent sham
      operation, and groups 3-6 were ovariectomized at the age of 21 months. Group 1
      was fed standard dog chow (calcium: 1.4%), and groups 2-6 were given a low
      calcium diet (0.14%). Groups 3 (n = 7), 4 (n = 7), 5 (n = 7), and 6 (n = 7) were
      given YM175 orally at doses of 0, 0.01, 0.1, and 1.0 mg/kg/day, respectively. At
      the end of the experimental period, bone mineral density values measured in the
      lumbar (L2) vertebra, the femoral neck, and the midfemur, were reduced in groups
      2 and 3. Bone strength, measured by compression tests on L2 body and L3
      cancellous core specimens and by bending tests on the femoral neck, also
      decreased. YM175 treatment dose-dependently increased the values of these
      parameters. However, the reduction in torsional stiffness in the midfemur was not
      completely prevented. In the L4 body, trabecular thickness decreased in group 2
      and trabecular separation increased in group 3. YM175 treatment prevented these
      changes, and the values in group 6 were maintained at the same levels as those in
      group 1. Bone formation rates were increased in groups 2 and 3. YM175 treatment
      decreased these indices, but the reduction was incomplete even with the highest
      dose (group 6). These results demonstrate that, in our model, YM175 maintained
      the mass, structure, and mechanical properties of cancellous bone. Increased bone
      turnover was not completely prevented by the doses employed, but the balance
      between net resorption and formation in one remodeling cycle would have been
      equilibrated by YM175.

PMID- 7572316
TI  - Intermittent cyclical etidronate treatment maintains the mass, structure and the
      mechanical property of bone in ovariectomized rats.
AB  - We examined the mechanical properties of rat bones treated with etidronate
      intermittent cyclic treatment (etidronate-ICT). Fifty Fisher rats, 7 months of
      age, underwent ovariectomy (OVX; n = 40) or sham operation (n = 10). The OVX rats
      were assigned to 4 groups injected with etidronate at the respective dose of 0,
      2, 4, or 8 mg/kg of body weight (bw) 5 days each week for 2 weeks, followed by a
      10-week period of no treatment. This regimen was repeated for 48 weeks. At the
      end of the treatment period, the ultimate bending strength and structural
      stiffness of the femoral midshaft in the OVX-alone group were not reduced
      compared with the values of the sham group, while those in the etidronate-treated
      groups were significantly larger than the values of the OVX group. The
      compressive stiffness and strength of the vertebral bodies specimens prepared
      from L3 and L5 vertebrae were markedly decreased in the OVX group compared with
      those in the sham group, but the values in the etidronate-treated groups were
      maintained at the same levels as those in the sham group. Mechanical properties
      at the tissue level, such as elastic modulus and material strength of the femoral
      cortex, were increased in etidronate-treated groups compared with the OVX group.
      The flexural modulus was also increased. The compressive elastic modulus of
      vertebral body in treated groups was preserved at the same level as that in the
      sham group. These results clearly demonstrate that in ovariectomized rats long
      term etidronate intermittent cyclic treatment preserves the mechanical properties
      both at the whole bone and the tissue level.

PMID- 7572317
TI  - Serum pyridinoline as a specific marker of collagen breakdown and bone metabolism
      in hemodialysis patients.
AB  - Type I collagen represents more than 90% of bone matrix. Quantitative analysis of
      collagen cross-link molecules such as pyridinoline (PYD) provides valuable
      information on bone resorption rate. We have studied 37 hemodialysis patients who
      underwent a systematic transiliac bone biopsy for histomorphometry study.
      Eighteen of them had tetracycline double labeling, allowing to determine dynamic,
      in addition to static bone parameters. Measurement of serum-free PYD was
      performed using a new competitive enzyme immunoassay. Serum PYD values were
      compared with those of three other serum markers of bone metabolism, namely
      intact PTH (iPTH), bone-specific alkaline phosphatase (bAP), and osteocalcin, for
      the correlations with bone histomorphometric parameters. Serum PYD levels (mean
      +/- SD) were significantly higher in dialysis patients than in normal
      individuals, 90.6 +/- 99.6 nM versus 1.9 +/- 0.4 nM, respectively. Patients with
      high turnover bone disease had significantly higher serum PYD levels than
      patients with normal or low bone turnover, 108.8 +/- 108.0 nM versus 34.1 +/-
      12.8 nM, respectively. Serum PYD levels were positively correlated with bone
      resorption parameters including osteoclast surface (r = 0.59, p < 0.0001) and
      osteoclast number/mm2 (r = 0.61, p < 0.0001), and also with bone formation
      parameters, osteoblast surface (r = 0.43, p < 0.008), double-labeled surface (r =
      0.81, p < 0.001), and BFR (r = 0.91, p < 0.0001). The BFR was better correlated
      with serum PYD levels than with either serum iPTH or osteocalcin concentrations.
      However, correlation with serum bAP was comparable.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7572318
TI  - Childhood growth, physical activity, and peak bone mass in women.
AB  - Peak bone mass is an important determinant of the risk of osteoporotic fracture,
      and preventive strategies against osteoporosis require a clear understanding of
      the factors influencing bone gain in early life. We report a longitudinal study
      aiming to identify the relationships between childhood growth, lifestyle, and
      peak bone mass in women. One hundred and fifty-three women born in a British city
      during 1968-1969 were traced and studied in 1990. Data on their growth in
      childhood was obtained from linked birth and school health records; current bone
      mineral measurements were made by dual X-ray absorptiometry. There were
      statistically significant associations between weight at 1 year and BMC (but not
      BMD) at the lumbar spine (r = 0.32, p < 0.01) and femoral neck (r = 0.26, p <
      0.01). These remained significant after adjusting for current weight. There were
      also strong relationships between childhood height measurements and adult BMC at
      the two skeletal sites. Physical activity was the major lifestyle determinant of
      BMD after allowing for body build. We conclude that infant growth and physical
      activity in childhood are important determinants of peak bone mass in women.
      Growth primarily determines the size of the skeletal envelope, and its trajectory
      is established by age 1 year. Activity, in contrast, modulates the mineral
      density within the skeletal envelope and may contribute to the consolidation of
      bone following the end of linear growth.

PMID- 7572319
TI  - A comparison of the anabolic effects of parathyroid hormone at skeletal sites
      with moderate and severe osteopenia in aged ovariectomized rats.
AB  - Previous studies have shown that parathyroid hormone (PTH) stimulates bone
      formation and completely restores lost cancellous bone at skeletal sites with
      moderate osteopenia in relatively young ovariectomized (OVX) rats. The current
      study was designed to determine whether PTH has similar bone anabolic effects in
      aged OVX rats and to compare the bone restorative response to PTH at skeletal
      sites with moderate and severe osteopenia. Female Sprague-Dawley rats were
      subjected to sham surgery or bilateral ovariectomy at 3 months of age and
      maintained untreated for the first year after surgery to allow for the
      development of moderate vertebral osteopenia and severe tibial osteopenia in OVX
      rats. Groups of baseline control and OVX rats were sacrificed at the end of this
      pretreatment period. The remaining OVX rats were then treated for 10 weeks with
      vehicle, antiresorptive agents alone (estrogen, the bisphosphonate risedronate,
      or calcitonin) or PTH alone. Other groups of OVX rats were treated concurrently
      with PTH and each of the antiresorptive agents. As expected, the proximal tibia
      of baseline OVX rats exhibited severe cancellous osteopenia, whereas the first
      lumbar vertebral body was moderately osteopenic. Treatment of OVX rats with
      antiresorptive agents alone failed to restore cancellous bone at both skeletal
      sites, whereas treatment with PTH alone markedly stimulated bone formation and
      completely restored lost cancellous bone in the lumbar vertebra. PTH also
      stimulated bone formation and in the severely osteopenic proximal tibia of OVX
      rats but only marginally restored lost cancellous bone, possibly due to an
      inadequate number of bone spicules to serve as a foundation for new bone
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572320
TI  - Interleukin-6 and the acute phase response during treatment of patients with
      Paget's disease with the nitrogen-containing bisphosphonate
      dimethylaminohydroxypropylidene bisphosphonate.
AB  - Bisphosphonates suppress bone resorption and are used in the management of bone
      diseases with increasing frequency. In some patients treated for the first time
      with potent nitrogen-containing bisphosphonates, there is a transient febrile
      reaction and transient hematological changes suggestive of an acute phase
      response. Because IL-6 is considered to be an important mediator of the acute
      phase response, we examined the changes in circulating IL-6 bioactivity in 38
      patients with Paget's disease treated with the nitrogen-containing bisphosphonate
      (3-dimethyl-amino-1-hydroxypropylidene)-1,1-bisphosphonate (dimethyl-APD). 16
      patients who had never received such bisphosphonate were treated with oral
      dimethyl-APD (100-400 mg/day) and 22 (9 for the first time) with intravenous
      dimethyl-APD 4 mg/day. Treatment was given for 10 days. Eleven of 38 patients,
      all first treatments, showed an increase in body temperature of more than 0.5
      degrees C exceeding 37 degrees C associated with a significant decrease in
      lymphocyte count and an increase in serum CRP values. These changes were
      transient and did not occur in the patients with no febrile response. In patients
      with a febrile reaction circulating IL-6 bioactivity increased significantly and
      this increase generally preceeded the rise in temperature. Moreover, patients
      with an acute phase response had significantly higher peak IL-6 values than those
      without (128 +/- 30 vs. 31 +/- 4 U/ml, p < 0.001). The peaks in plasma IL-6 were
      further correlated with the peaks in temperature and in serum CRP values (r =
      0.49, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572321
TI  - Extra cancellous bone induced by combined prostaglandin E2 and risedronate
      administration is maintained after their withdrawal in older female rats.
AB  - Prostaglandin E2 (PGE2) has been recognized for its marked anabolic effect on
      bone, but the bone gain is lost after the cessation of PGE2 treatment. In
      previous studies, we were successful in maintaining the new bone by administering
      a bisphosphonate after the withdrawal of PGE2 treatment. The objective of this
      study was to determine the fate of the extra bone induced by a combination with
      PGE2 and risedronate after discontinuing treatment. Ninety-six 9-month-old virgin
      female Sprague-Dawley rats were treated with 1 or 5 micrograms of
      risedronate/kg/twice weekly, 6 mg of PGE2/kg/day alone or 6 mg of PGE2/kg/day
      plus 1 or 5 micrograms of risedronate/kg/twice weekly for 60 days (day 0) and
      followed by 60 days without treatment (day 60). We have reported the results from
      the groups treated for 60 days previously. This report is restricted to the
      histomorphometric findings on the secondary spongiosa of the proximal tibial
      metaphysis in the groups after withdrawal for 60 days. We found that the only
      group that maintained the PGE2 induced new bone after withdrawal was the group
      treated with 6 mg of PGE2/kg/day plus 5 micrograms of risdronate/kg/twice a week.
      Withdrawal of this combined treatment depressed bone turnover (bone-based bone
      formation rate, activation frequency) and bone resorption (percent eroded
      perimeter). The tissue mechanisms responsible for the protection drew from the
      previously deposited risedronate.

PMID- 7572322
TI  - Short-term local injections of transforming growth factor-beta 1 decrease
      ovariectomy-stimulated osteoclastic resorption in vivo in rats.
AB  - Estrogen deficiency in rats is responsible for increased osteoclastic resorption
      and a subsequent rapid bone loss. TGF-beta, which is known to have acute effects
      on bone resorption in several in vitro models, has been shown to be secreted by
      osteoblastic cells in vitro in response to 17 beta-estradiol, but little is known
      about its in vivo effects on bone resorption. We therefore decided to investigate
      the short-term effect of TGF-beta 1 on bone resorption in ovariectomized rats.
      TGF-beta 1 (0.04-20 ng/injection), or vehicle, was injected daily directly into
      the bone marrow space, through a thin catheter implanted in the distal end of the
      right femur, during 4 consecutive days, starting 14 days after the ovariectomy.
      Bone histomorphometry was performed in the secondary spongiosa of the metaphysis
      of injected femurs and compared with vehicle-injected femurs of sham
      ovariectomized rats. Ovariectomy was associated with a marked increase in the
      resorption surface, a 2-fold increase in the number of osteoclasts, and no change
      in the number of TRAP-positive marrow cells distant from bone surfaces. Bone
      resorption was significantly lower in the TGF-beta 1-injected bones of
      ovariectomized rats, as compared with vehicle injected bones: the osteoclast
      surface and the number of osteoclasts were, respectively, 11.0 +/- 5.1% versus
      20.8 +/- 1.3% and 287 +/- 41 versus 505 +/- 53, in bones injected with 0.2 ng of
      TGF-beta 1 as compared with vehicle-injected bones (mean +/- SE, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572323
TI  - Vitamin D receptor alleles and rates of bone loss: influences of years since
      menopause and calcium intake.
AB  - A genetic marker for the 1,25-dihydroxyvitamin D receptor (VDR) is reported to
      account for much of the heritable component of bone density. It is not known
      whether VDR genotype influences bone accretion or loss, or how it is related to
      calcium metabolism. The VDR genotype was determined in 229 healthy postmenopausal
      women who previously participated in a calcium trial. VDR alleles were designated
      according to presence (b) or absence (B) of the BsmI restriction enzyme cutting
      site. There were 83 bb, 102 Bb, and 44 BB individuals. Two-thirds of the women
      took 500 mg of calcium supplement (mean calcium intake = 892 mg/day) and one
      third a placebo (mean = 376 mg/day). Bone mineral density (BMD) at the femoral
      neck, spine, and radius were measured by dual- and single-photon absorptiometry
      at baseline and after 1 and 2 years. Among women more than 10 years
      postmenopausal, those with the BB genotype had the lowest femoral neck BMD. Rates
      of bone loss over 2 years were greater in the BB group at all sites (e.g., at the
      femoral neck, bb, 0.45 +/- 0.43; Bb, -0.01 +/- 0.40; BB, -0.99 +/- 0.50%/year; BB
      vs. bb, p = 0.01), and this trend was found both in women < 10 years since
      menopause (e.g., at the radius, bb, 0.43 +/- 0.47; Bb, -0.37 +/- 0.42; BB, -1.20
      +/- 0.59% per year; BB vs. bb, p = 0.02) and those > or = 10 years (radius, bb, 
      0.71 +/- 0.41; Bb, 0.08 +/- 0.39; BB, -1.41 +/- 0.49% per year; BB vs. Bb, p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572324
TI  - The BsmI vitamin D receptor restriction fragment length polymorphism (BB)
      predicts low bone density in premenopausal black and white women.
AB  - We conducted a study to determine whether a recently described restriction
      fragment length polymorphism in the vitamin D receptor gene (VDR-RFLP) predicts
      bone mineral density (BMD) in unrelated, premenopausal women as well as to
      determine the racial contribution to any genotypic influences on BMD. White (n =
      83) and black (n = 72) women between 20 and 40 years of age were genotyped based
      on the presence (b) or absence (B) of a BsmI restriction enzyme site in the VDR
      gene, and BMD in the lumbar spine and femur neck was determined for each subject.
      There were 16 BB, 73 Bb, and 66 bb women. No significant difference was observed
      in genotypic distribution between the racial groups. The interaction of race by
      genotype on age- and body mass index (BMI)-adjusted BMD was not significant at
      either site. Age- and BMI-adjusted BMD was higher in black women at the spine (by
      7.2%, p = 0.046) and femur neck (7.3% higher, p = 0.004). In the group as a
      whole, mean BMD in the femur neck was lower in the BB women that the bb (by 8.1%,
      p = 0.034) or Bb women (by 9.3%, p = 0.015) after controlling for age, BMI, race,
      and the race by genotype interaction. Adjusted lumbar spine BMD was lower in the
      BB women than the Bb women (6.4% lower, p = 0.036) in the group as a whole. No
      difference were detected between Bb and bb women at either site. A similar
      pattern of low BMD at the femur neck and the lumbar spine was seen in BB women of
      both races.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572326
TI  - Universal standardization for dual X-ray absorptiometry: patient and phantom
      cross-calibration results.

PMID- 7572327
TI  - Involvement of opioid peptides of the preoptic area during electroacupuncture
      analgesia.
AB  - The present work was to study the roles of opioid peptides in the preoptic area
      on electroacupuncture analgesia (EA), and the effects of opioid peptides on
      noradrenaline (NA) release in the preoptic area during EA. It was found that the
      pain threshold and the level of [Leu5] enkephalin (L-EK) or beta-endorphin (beta
      EP) release in the perfusate were increased during EA, but the NA release from
      the preoptic area was decreased. Naloxone (15 microM) perfusion significantly
      reversed the increased pain threshold and the decreased NA release induced by
      acupuncture. The reversal of pain threshold and the decreased NA release induced
      by acupuncture. The reversal of pain threshold and NA release by naloxone was
      dose-dependent. Multimicropipettes and microiontophoresis were also used to study
      the effect of acupuncture. The inhibition of nociceptive neuronal discharges
      produced by electroacupuncture was closely related to the etorphine-sensitive
      neurons, and reversed by microiontophoretic application of naloxone. The results
      suggest that the inhibitory effect induced by electroacupuncture may be mediated
      by opioid peptides in the preoptic area.

PMID- 7572328
TI  - A neuromagnetic study of acupuncturing LI-4 (Hegu).
AB  - The brain magnetic fields evoked by acupuncturing LI-4(Hegu) were measured by
      using SQUID (superconductive Quantum Interference Device) Biomagnetometer, and
      the morphological characters of these biomagnetic fields were examined in 12
      subjects. The observed phenomenon of the LI-4(Hegu)'s projection area overlapping
      on the jaw's and face's projection area suggests that excitation of LI-4 (Hegu)'s
      projection area activated by acupuncturing LI-4(Hegu) could inhibit action of the
      jaw's and face's projection through the overlapping area, and this is the reason
      why the acupuncturing LI-4(Hegu) could effectively case pains in the treatment of
      dental pain.

PMID- 7572325
TI  - The contribution of vitamin D receptor gene alleles to the determination of bone
      mineral density in normal and osteoporotic women.
AB  - Bone mass and its mineral content are under genetic control. The vitamin D
      receptor (VDR) gene has been shown to be a major locus for genetic effects on
      bone mineral density (BMD), and polymorphisms in this gene accounted for a large
      proportion of genetic variance in BMD in an Australian population. In this study,
      we investigated whether similar associations are present in a North American
      population. We studied 139 normal healthy women (age 53.2 +/- 14.5, mean +/- SD)
      and 43 severely osteoporotic postmenopausal women (age 65.8 +/- 5.9). In the 127
      of them with complete genetic studies, the distribution of genotypes, determined
      by polymerase chain reaction on leukocyte DNA samples, agreed closely with that
      in the Australian population. BMD was strongly related to age and weight, and,
      thus was adjusted for these parameters prior to genetic analysis. We found that
      age modulated the effect of VDR genotypes on femoral neck BMD (FN-BMD) (TaqI, p =
      0.036; BsmI, p = 0.118; ApaI, p = 0.041) such that the effect of genotype was
      greatest among younger (premenopausal) women and declined with age so that there
      was no discernible difference by age 70. Among the younger women, a high FN-BMD
      was associated with the TT (or aa or bb) genotype while low FN-BMD was associated
      with the tt (or AA or BB) genotype.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572330
TI  - A clinical study on SSP (silver spike point) electro-therapy combined with splint
      therapy for temporo-mandibular joint dysfunction.
AB  - When the functional limits of the muscles related to the temporo-mandibular joint
      and adjacent tissue exceed their anatomical capability, pain, crepitation, and
      functional abnormality appear as the main complaints. Although the precise nature
      of the condition is unknown, pain at the temporo-mandibular joint sometimes in
      combination with muscular tension is assumed to be due to compression of the
      myoneural mechanism. It is reported that occlusal lifting using a splint enables
      the alleviation of this muscular tension. On the other hand, there are only a few
      reports on the usefulness of SSP therapy for Temporo-Mandibular Joint
      Dysfunction. We studied the efficacy of SSP therapy combined with splint therapy
      in 33 patients diagnosed as having Temporo-Mandibular Joint Dysfunction who
      consulted our department primarily due to pain, and report our findings below.
      Evaluation of the results was conducted 2 weeks later. Very beneficial results
      were seen in 6 cases. Beneficial results were seen in 7 cases. Slightly
      beneficial results were seen in 18 cases, while there were no changes found in 2
      cases. When combined SSP and splint therapies were conducted for Temporo
      Mandibular Joint Dysfunction, favorable results were seen in about 90% of the
      cases.

PMID- 7572329
TI  - Application of intensified (+) Qi Gong energy, (-) electrical field, (S) magnetic
      field, electrical pulses (1-2 pulses/sec), strong Shiatsu massage or acupuncture
      on the accurate organ representation areas of the hands to improve circulation
      and enhance drug uptake in pathological organs: clinical applications with
      special emphasis on the "Chlamydia-(Lyme)-uric acid syndrome" and "Chlamydia
      (cytomegalovirus)-uric acid syndrome".
AB  - Various methods of improving circulation and enhancing drug uptake which were
      used in treating some intractable medical problems caused by infections, and two
      syndromes based on the co-existence of Chlamydia trachomatis infection (mixed
      with either Lyme Borrelia burgdorferi or Cytomegalovirus) with increased Uric
      acid are described. The principal author's previous studies have indicated that
      there are two opposite types of Qi Gong energy, positive (+) and negative (-).
      Positive (+) Qi Gong energy has been used clinically to enhance circulation and
      drug uptake in diseased areas where there is a micro-circulatory disturbance and
      drug uptake is markedly diminished. (-) Qi Gong energy has completely the
      opposite effect and therefore has not been used although there may be some as yet
      undiscovered application. Since the late 1980's the principal author has
      succeeded in storing (+) Qi Gong energy on a variety of substances including
      small sheets of paper, and recently has been able to intensify this energy by
      concentrating it as it passes through a cone-shaped, tapered glass or plastic
      object placed directly on the (+) Qi Gong energy stored paper. Application of (+)
      Qi Gong energy stored paper on the cardio-vascular representation area of the
      medulla oblongata at the occipital area of the skull often improved circulation
      and enhanced drug uptake. If the drug-uptake enhancement was still not sufficient
      for the drug to reach therapeutic levels in the diseased organ, direct
      application of (+) Qi Gong from the practitioner's hand often enhanced the drug
      uptake more significantly. However, this direct method often results in the
      practitioner developing intestinal micro-hemorrhage within 24 hours which may or
      may not be noticed as mild intestinal discomfort with soft, slightly tarry stool.
      For intensifying (+) Qi Gong energy one of the most efficient shapes is a cone
      with increased intensification occurring at an optimal height. However when the
      total mass and the total distance from base to peak is increased beyond an
      optimal limit, the power decreases. Clinical application of Intensified (+) Qi
      Gong stored energy was evaluated in this preliminary study which indicated that
      intensified (+) Qi Gong energy application on the heart representation area of
      the middle finger on the hands markedly improved circulation in the corresponding
      organ, and increased drug uptake and acetylcholine even more effectively than
      some of the previously used drug enhancement methods (Shiatsu massage of the
      organ representation areas and/or application of (+) Qi Gong energy stored paper
      to the occipital area above the cardiovascular representation area of the medulla
      oblongata).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572331
TI  - Comparative anatomy of the external and middle ear of palaeognathous birds.
AB  - This study provides new anatomical data, morphometric measurements, and
      functional hypotheses about the middle ear of paleognathous and a basal
      neognathous bird. The introduction discusses current theoretical concepts and
      basic functional approaches in vertebrate morphology. A cautious and somewhat
      skeptical evaluation of the techniques used, errors made, and personal experience
      gained in this study forms the background of the interpretation of the structural
      data. The comparative discussion extracts phylogenetic information from the
      structural data. The external ear opening of paleognathous species is large and
      unprotected. The auricular feathers show no structural specialization and provide
      only incomplete opercularization. No muscles insert into the external ear
      opening. Special attention has been paid to modifications in the cassowary's
      skin. The skin of its head has developed cavernous blood sinuses that may be
      flooded and thus inflate the head during booming display. The external auditory
      meatus of paleognathous birds is large, bends ventrally, and reaches the tympanic
      membrane from the ventral side. No peculiarities can be described. The osteology
      of the tympanic region is described in detail. The fusion of all bony elements
      and the ossification of connective tissue are important features of the avian
      middle ear region. The fusion of bone is a necessary prerequisite for extended
      pneumatization. The ossification of connective tissue, however, complicates
      morphological description since it deviates from morphologically defined bones.
      Especially in the neognathous button quail, most of the ventral wall of the
      middle ear cavity consists of ossified connective tissue; it also includes
      elements of the extracolumella. The fixation of the eardrum to the bony wall of
      the tympanic cavity is described in detail. The fixation includes the kinetic
      quadrate and loose connective tissue in the ventro-lateral part of the middle ear
      cavity. Movements of the bill must change the tension of the eardrum and thus
      affect the hearing of birds. The recesses of the middle ear cavity have been
      investigated using X-ray computed tomography. Using this technique, subsequent
      three-dimensional reconstruction provides unusual and unique insights into the
      anatomy of such "nonstructures" as air-filled cavities. It has been shown that
      three tympanic recesses are a character shared by all birds. Of more functional
      importance is the interaural pathway provided by the anterior tympanic recess and
      connecting the contralateral middle ear cavities. This structure is present in
      all recent and mesozoic birds. It has been suggested that the interaural pathway
      might function as a sound pressure gradient receptor. Physiological data are
      controversial but in many cases supportive.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572332
TI  - Microbial oxidation of unsaturated fatty acids.

PMID- 7572333
TI  - Biotechnological potentials of anoxygenic phototrophic bacteria. I. Production of
      single-cell protein, vitamins, ubiquinones, hormones, and enzymes and use in
      waste treatment.

PMID- 7572334
TI  - Biotechnological potentials of anoxygenic phototrophic bacteria. II.
      Biopolyesters, biopesticide, biofuel, and biofertilizer.

PMID- 7572335
TI  - Improving productivity of heterologous proteins in recombinant Saccharomyces
      cerevisiae fermentations.

PMID- 7572336
TI  - Manipulations of catabolic genes for the degradation and detoxification of
      xenobiotics.

PMID- 7572337
TI  - Regulation of signal transduction.
AB  - 1. A systematic study is reported on the control of 1-phosphatidylinositol 4
      kinase (PI kinase) and PI 4-phosphate 5-kinase (PIP kinase), enzymes of the
      phosphatidylinositol phosphorylation pathway which leads to the production of
      second messengers. IP3 and DAG. In liver of normal male, adult, fed Wistar rats
      the steady state activity of PI kinase was 0.5 +/- 0.01 and that of PIP kinase
      was 0.046 +/- 0.003 nmol/hr/mg protein. The concentration of IP3 was 1.8 +/- 0.1
      pmol/mg protein. 2. That the two kinases have short half-lives was observed in
      starvation. where in the rat liver or bone marrow activities rapidly decreased
      and on refeeding were restored in a day. Injection to rats of the protein
      synthetic inhibitor, cycloheximide, yielded t1/2 = 80 min for the two enzymes in
      bone marrow and t1/2 = 80 min in liver. 3. Linkage of the signal transduction
      enzymes with proliferation was shown by the high activities as compared to liver
      of these enzymes in rat organs of high cell renewal capacity, e.g., thymus, bone
      marrow, spleen and testes. 4. Linkage with malignant proliferation was indicated
      by the observation that in rat hepatomas the enzyme activities increased 5- to 9
      fold and were highest in rapidly growing hepatoma 3924A (29- and 45-fold). 5. In
      human primary ovarian carcinoma PI and PIP kinase activities were elevated 4.4
      and 2.9-fold, respectively, and in OVCAR-5 cells, 32- and 11-fold, respectively.
      Similar increases were observed in MDA-MB-435 human breast carcinoma cells in
      comparison with normal breast parenchymal cells. 6. The linkage of signal
      transduction enzyme activities with malignant proliferation was also observed in
      experiments when human breast carcinoma cells were plated in flasks and expressed
      their proliferative capacity in the log phase. PI and PIP kinase activities
      steadily and coordinately increased to a peak 11-fold rise in mid-log phase. In
      late log and plateau phases the kinase activities gradually declined to the
      starting level. Similar observations were made for the two enzymes in human
      ovarian carcinoma OVCAR-5 cells and in rat hepatoma 3924A cells in tissue
      culture. 7. In animals injected with cycloheximide the bone marrow PI and PIP
      kinase activities exhibited t1/2 = 0.12 hr, the shortest decay rate in comparison
      with 8 enzymes of purine and pyrimidine biosynthesis with t1/2 = 0.6 to 4.3 hr.
      8. Injection of tiazofurin decreased PI and PIP kinase activities in the bone
      marrow with t1/2 = 82 and 78 min, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572338
TI  - Tumor metabolism: the lessons of magnetic resonance spectroscopy.
AB  - For many years after Warburg's classic work, it was generally assumed that tumors
      produced large amounts of lactic acid and consequently had an acidic
      intracellular pHi. However, with the advent of Magnetic Resonance Spectroscopy
      (MRS), a non-invasive in vivo measure of tissue pH became available and
      demonstrated that in both human and animal tumors, pHi was higher (> 7.0) than pH
      epsilon (< 6.8), in contrast to normal tissues (e.g., liver) in which pHi
      (approximately 7.2) is lower than pH epsilon (approximately 7.4). This result has
      been confirmed in animal tumors using an MRS-visible extracellular marker, 3
      aminopropyl phosphonate. The pH gradient across the tumor cell membrane is part
      of an interrelated system of ionic gradients and measurements made by both 31P
      MRS and by conventional analysis in Morris hepatoma 9618a and in livers
      demonstrated that the following ions also changed: compared with liver the Na+
      content was 2-fold higher, K+ was 20% lower, total Ca2+ was 8-fold higher (7.4
      mumol/g wet wt) and total Pi 2-fold higher (8.5 mumol/g wet wt), suggesting the
      presence of insoluble calcium phosphate, HCO3- was lower, total Mg2+ was similar
      in both tissues, but free [Mg2+] (calculated by two different methods) was
      approximately 5-fold lower in the hepatoma, as was [ATP]/[ADP][P(i)]. Because of
      an inadequate blood supply, tumors are often hypoxic with impaired Krebs cycle
      activity, low [ATP]/[ADP][P(i)] and rely mainly on glycolysis for energy. The
      rapid production and subsequent export of anionic lactate-from the tumor cell
      would be accompanied by H+. This would account for reversal of the proton
      gradient and activation of the Na+/H+ exchange. The elevated [Na+]i would
      decrease the Na+/Ca2+ exchange, which would in turn tend to cause the
      accumulation of Ca2+ (and P(i)). Such calcification is a very common feature of
      tumor pathology. The data indicate the change in gradient of one ion (H+)
      involves alterations in the linked equilibria of many ions and also of energy
      metabolites and offers new insights into properties of tumors important both
      diagnostically and therapeutically.

PMID- 7572339
TI  - Preferential kill of hypoxic EMT6 mammary tumor cells by the bioreductive
      alkylating agent porfiromycin.
AB  - Hypoxic cells in solid tumors represent a therapeutically resistant population
      that limits the curability of many solid tumors by irradiation and by most
      chemotherapeutic agents. The oxygen deficit, however, creates an environment
      conducive to reductive processes; this results in a major exploitable difference
      between normal and neoplastic tissues. The mitomycin antibiotics can be
      reductively activated by a number of oxidoreductases, in a process required for
      the production of their therapeutic effects. Preferential activation of these
      drugs under hypoxia and greater toxicity to oxygen-deficient cells than to their
      oxygenated counterparts are obtained in most instances. The demonstration that
      mitomycin C and porfiromycin, used to kill the hypoxic fraction, in combination
      with irradiation, to eradicate the oxygenated portion of the tumor, produced
      enhanced cytodestructive effects on solid tumors in animals has led to the
      clinical evaluation of the mitomycins in combination with radiation therapy in
      patients with head and neck cancer. The findings from these clinical trials have
      demonstrated the value of directing a concerted therapeutic attack on the hypoxic
      fraction of solid tumors as an approach toward enhancing the curability of
      localized neoplasms by irradiation.

PMID- 7572340
TI  - Hormonal control of hepatic glutaminase.
AB  - (1) Glucagon activates hepatic glutaminase in vivo. Mitochondria from glucagon
      injected rats retain an enhanced capacity to catabolize glutamine and this is
      more sensitive to activation by inorganic phosphate. The glucagon-elicited
      stimulation of glutaminase is not evident in broken mitochondria. A similar
      activation of glutaminase occurs in a number of situations which are associated
      with elevated glucagon levels in vivo, i.e., after a high-protein meal, after
      injection of bacterial endotoxin and in diabetes mellitus. (2) Studies in
      isolated hepatocytes revealed that glutaminase could be activated, not only by
      glucagon, but also by a cell-permeable protein kinase A activator (Sp-cAMPS) and
      by a cell-permeable protein phosphatase 1 and 2A inhibitor (okadaic acid).
      However, the activation of glutaminase by glucagon was not inhibited by a cell
      permeable protein kinase A inhibitor (Rp-8-Br-cAMPS). We suggest that the
      signalling pathway, for glutaminase activation by glucagon, is complex and
      possibly contains redundant elements.

PMID- 7572341
TI  - A new family of protein kinases--the mitochondrial protein kinases.
AB  - Molecular cloning has provided evidence for a new family of protein kinases in
      eukaryotic cells. These kinases show no sequence similarity with other eukaryotic
      protein kinases, but are related by sequence to the histidine protein kinases
      found in prokaryotes. These protein kinases, responsible for phosphorylation and
      inactivation of the branched-chain alpha-ketoacid dehydrogenase and pyruvate
      dehydrogenase complexes, are located exclusively in mitochondrial matrix space
      and have most likely evolved from genes originally present in respiration
      dependent bacteria endocytosed by primitive eukaryotic cells. Long-term
      regulatory mechanisms involved in the control of the activities of these two
      kinases are of considerable interest. Dietary protein deficiency increases the
      activity of branched-chain alpha-ketoacid dehydrogenase kinase associated with
      the branched-chain alpha-ketoacid dehydrogenase complex. The amount of branched
      chain alpha-ketoacid dehydrogenase kinase protein associated with the branched
      chain alpha-ketoacid dehydrogenase complex and the message level for branched
      chain alpha-ketoacid dehydrogenase kinase are both greatly increased in the liver
      of rats starved for protein, suggesting increased expression of the gene encoding
      branched-chain alpha-ketoacid dehydrogenase kinase. The increase in branched
      chain alpha-ketoacid dehydrogenase kinase activity results in greater
      phosphorylation and lower activity of the branched-chain alpha-ketoacid
      dehydrogenase complex. The metabolic consequence is conservation of branched
      chain amino acids for protein synthesis during periods of dietary protein
      deficiency. Two isoforms of pyruvate dehydrogenase kinase have been identified
      and cloned. Pyruvate dehydrogenase kinase 1, the first isoform cloned,
      corresponds to the 48 kDa subunit of the pyruvate dehydrogenase kinase isolated
      from rat heart tissue. Pyruvate dehydrogenase kinase 2, the second isoform
      cloned, corresponds to the 45 kDa subunit of this enzyme. In addition, it also
      appears to correspond to a possibly free or soluble form of pyruvate
      dehydrogenase kinase that was originally named kinase activator protein. Assuming
      that differences in kinetic and/or regulatory properties of these isoforms exist,
      tissue specific expression of these enzymes and/or control of their association
      with the complex will probably prove to be important for the long term regulation
      of the activity of the pyruvate dehydrogenase complex. Starvation and the
      diabetic state are known to greatly increase activity of the pyruvate
      dehydrogenase kinase in the liver, heart and muscle of the rat. This contributes
      in these states to the phosphorylation and inactivation of the pyruvate
      dehydrogenase complex and conservation of pyruvate and lactate for
      gluconeogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572342
TI  - Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in
      human adipose tissue in vivo: implications for the control of fat storage and fat
      mobilization.
AB  - The enzymes lipoprotein lipase (LPL, EC 3.1.1.34) and hormone-sensitive lipase
      (HSL, EC 3.1.1.3) apparently catalyze opposing functions in white adipose tissue:
      the former is concerned with fat storage, the latter with fat mobilization. We
      have studied their regulation in vivo in normal subjects in the postabsorptive
      state and after eating meals of different compositions, by measurement of
      arteriovenous concentration differences for triacylglycerol, non-esterified fatty
      acids and glycerol across a subcutaneous adipose depot. The two enzymes are
      regulated in a broadly reciprocal manner: in the overnight-fasted state, HSL is
      more active, but after a meal HSL is suppressed whilst LPL is activated. The
      movement of fatty acids in and out of adipose tissue appears to be driven by
      concentration gradients generated by regulation of these two enzymes, and also by
      activation, in the postprandial period, of the process of fatty acid
      esterification. The results show some interesting and perhaps unexpected features
      of metabolic regulation. Of the fatty acids generated by the action of LPL on
      circulating TAG, a large proportion is released directly into the venous plasma:
      close to 100% in the overnight-fasted state, and 50% or more at the peak of LPL
      action after a meal, making what appear reasonable assumptions. We suggest that
      this apparent 'inefficiency' of fat storage reflects the energetic cost of
      maintaining precise control over such a fundamental process. Although LPL is
      usually thought of as the enzyme regulating fat deposition, in fact the fatty
      acids and glycerol it releases from circulating TAG represent a substantial
      proportion of those released from adipose tissue, especially in the postprandial
      state. In addition, although HSL is considered the enzyme responsible for fat
      mobilization, suppression of its activity is essential to normal regulation of
      fat deposition. Thus, fat storage and fat mobilization during normal daily life
      are controlled by coordinated regulation of a number of enzymatic processes in
      white adipose tissue.

PMID- 7572343
TI  - Intracellular triacylglycerol lipase: its role in the assembly of hepatic very
      low-density lipoprotein (VLDL).
AB  - Extracellular fatty acids entering the hepatocyte are either esterified to
      cytosolic TAG or oxidized to ketone bodies. Very little is esterified and
      secreted directly in association with VLDL. Thus, even when extracellular fatty
      acids are available, the major, direct source of VLDL TAG is the cytosolic pool.
      The recruitment of cytosolic TAG for VLDL assembly involves lipolysis followed by
      re-esterification. At least 70% of the secreted TAG is derived via this route.
      Fatty acids released at this lipolytic step are utilized exclusively for VLDL TAG
      synthesis and are not available for ketogenesis. Substantially more cytosolic TAG
      undergoes lipolysis than is required to meet the needs of VLDL assembly. The
      remaining fatty acids are re-esterified and re-cycled to the cell cytosol. From a
      physiological viewpoint, the presence of this indirect route for VLDL TAG
      recruitment would provide a means of regulation of VLDL secretion which is
      independent of the plasma fatty acid concentration. In this respect, several
      pathophysiological conditions are known in which there is a negative association
      between plasma fatty acid concentration and the rate of VLDL secretion. These
      are: (a) insulin-dependent diabetes, (b) starvation, (c) fat-feeding. Lipolysis
      of cytosolic TAG and transfer of fatty acids into the ER lumen may provide a
      regulatory focus for the control of hepatic VLDL output.

PMID- 7572344
TI  - Microfilament dynamics: regulation of actin polymerization by actin-fragmin
      kinase and phosphatases.
AB  - Based on the phosphorylation of the purified actin-fragmin complex, an 80 kDa
      monomeric kinase (AFK) has been isolated from Physarum polycephalum. Protein
      chemical analysis and studies involving kinase inhibitors and effectors establish
      that the AFK is a unique kinase that cannot be classified so far in one of the
      conventional kinase families. The actin-fragmin kinase behaves as an
      "independent" kinase since its activity towards the actin-fragmin complex is
      apparently not regulated by the binding of a ligand (e.g., the cyclic
      nucleotides, Ca2+, calmodulin, phosphatidylserine and diolein). Rigorous
      screening of the substrate specificity suggests that the actin-fragmin complex
      represents the only substrate for this kinase. This kinase phosphorylates the
      actin moiety of the actin-fragmin complex at two consecutive threonine residues
      which constitute one of the contact sites for DNase I (37) and which are also
      located at one of the proposed actin-actin contact sites along the long-pitch
      helix of F-actin (38, 39). The physiological importance of this phosphorylation
      was demonstrated by studying the effect of phosphorylation on the nucleation and
      the capping activity of the actin-fragmin complex using fluorescence enhancement
      analysis. As could be demonstrated, the nucleation of actin filaments by the
      actin-fragmin complex is completely abolished upon phosphorylation by the AFK.
      Phosphorylation of the complex also interferes with its capping activity, which
      becomes Ca(2+)-dependent. In addition, capping and nucleating activity is
      regulated in vitro by phosphoinositides, of which PIP2 displays the highest
      activity and specificity. PIP2 partially inhibits the nucleation and capping
      activity of the unphosphorylated actin-fragmin. The capping activity of the
      phosphorylated actin-fragmin complex was inhibited by PIP2 to a much greater
      extent as compared to the unphosphorylated actin-fragmin complex. Among all
      phospholipids tested, PIP2 displayed the highest specificity. Initial experiments
      with purified preparations of the PP-1, PP-2A, PP-2B, alkaline phosphatase and
      acid phosphatases showed that PP-1 and PP-2A phosphatases were capable of
      dephosphorylating the phospho actin-fragmin complex. These findings raised the
      question of whether these or other protein phosphatases were involved in the
      dephosphorylation of this substrate in vivo. To address this question, Physarum
      extracts were subjected to fractionation by ion exchange chromatography, and the
      column fractions were assayed in a variety of conditions, to identify the protein
      phosphatases involved in the dephosphorylation of this substrate and to identify
      the elution position of the major Ser/Thr protein phosphatases present in the
      Physarum extract.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572346
TI  - Nuclear inositol lipid cycle and differentiation.
AB  - Previous investigations from our laboratory and others have shown the existence
      of an autonomous intranuclear inositide cycle endowed with conventional lipid
      kinases and PLC which in PC12 pheochromocytoma cells, human osteosarcoma SaOS-2
      cells, rat liver and Swiss 3T3 cells is the isoform beta 1, which in the latter
      cells is activated upon IGF-I stimulation. The behavior of the nuclear inositol
      lipid cycle has been investigated in nuclei of Friend erythroleukemia cells.
      These nuclei possess both lipid kinases and PLC. The cycle upon treatment with
      differentiating agents (i.e., DMSO and tiazofurin) is characterized by an
      accumulation of polyphosphoinositides and a decrease of DAG due to down
      regulation of a specific PLC. Indeed, even if both beta 1 and gamma 1 isoforms
      are present in these nuclei, when Friend cells undergo terminal erythroid
      differentiation only the PLC beta 1 isoform is down-regulated as shown by
      immunochemical and immunocytochemical analysis, by direct determination of
      enzymatic activity and in the presence of neutralizing monoclonal antibodies as
      well as by Northern blot for PLC beta 1 message, whilst the amount of PLC gamma 1
      and its activity are unaffected by erythroid differentiation. In conclusion, the
      presence of a specific nuclear PLC whose activity and expression are down
      regulated during differentiation of erythroleukemia cells points out a role for
      nuclear phosphoinositide signalling in the processes of cell differentiation and
      hints at the nuclear PLC beta 1 as an important step of the cycle in relation to
      the erythroid differentiative commitment of murine erythroleukemia cells.

PMID- 7572345
TI  - Mammalian phosphoribosyl-pyrophosphate synthetase.
AB  - PRPP synthetase from rat liver exists as large molecular weight aggregates
      composed of at least three different components. Cloning of cDNA for the
      catalytic subunit revealed the presence of two highly homologous isoforms of 34
      kDa, designated as PRS I and PRS II. Northern blot analysis showed tissue
      differential expression of the two isoform genes. cDNA was expressed in E. coli
      and studies on the recombinant isoforms showed differences in sensitivity to
      inhibition by ADP and GDP and to heat inactivation. The rat gene for PRS I has 22
      kb and is split into 7 exons. cDNAs for human enzymes were also cloned. Human
      genes for PRS I and PRS II are localized at different regions on the X-chromosome
      and their promoter regions were examined. Another component, PRPP synthetase
      associated protein of 39 kDa (PAP39), was cloned from cDNA library of the rat
      liver. The deduced amino acid sequence of PAP39 is remarkably similar to those of
      PRS I and PRS II. Evidence indicated molecular interaction between PAP39 and the
      catalytic subunits and an inhibitory effect of PAP39 on the catalytic activity.
      Expression of the PAP39 gene is tissue-differential like the PRS genes,
      indicating that the composition of PRPP synthetase may differ with the tissue,
      hence properties of the enzyme would differ. Further studies on these components
      and their interaction are expected to reveal various mechanisms governing
      mammalian PRPP synthetase.

PMID- 7572348
TI  - DNA topoisomerase II isozymes involved in anticancer drug action and resistance.
AB  - DNA topoisomerase II is a major protein of the nuclear matrix. The enzyme appears
      to have a central role in both DNA organization and replication. The importance
      of nuclear matrix topoisomerase II alpha as a target for certain anticancer
      agents was evaluated in CEM human leukemia cells. Studies were done to determine
      the extent to which the alpha (170 kDa) and beta (180 kDa) isozymes of
      topoisomerase II form covalent enzyme-DNA complexes in whole cells and in the
      nuclear matrix and nonmatrix fractions of CEM cells that are either sensitive or
      resistant to topoisomerase II-active anticancer agents. Topoisomerase II alpha
      was detected in both the high salt-soluble (nonmatrix) and matrix fractions of
      nuclei from parental CEM cells. Most of the matrix topoisomerase II alpha was
      tightly bound to DNA in cells incubated with VM-26. In contrast, topoisomerase II
      beta was detected only in the high salt-soluble (nonmatrix) fraction of the
      nucleus. The subnuclear distribution of the alpha and beta topoisomerase II
      isozymes in CEM/VM-1 cells resistant to topoisomerase-active drugs was similar to
      that in drug-sensitive CEM cells. However, the amount and activity of
      topoisomerase II alpha in nuclear matrices of CEM/VM-1 cells were decreased 3- to
      6-fold relative to that of CEM cells. The differences observed in the subnuclear
      distribution and DNA binding pattern of the topoisomerase II isozymes support the
      hypotheses that each isozyme has a distinct cellular function. Furthermore, these
      results provide evidence that topoisomerase II alpha is the nuclear matrix target
      for VM-26, and that depletion of the nuclear matrix isozyme contributes to
      cellular resistance to this anticancer agent.

PMID- 7572347
TI  - Thiopurine induced disturbance of DNA methylation in human malignant cells.
AB  - The studies described indicate that me-t-IMP formation is an important pathway,
      contributing to cytotoxicity in Molt F4 cells, which exhibit a highly active de
      novo purine synthesis. On three levels cytotoxicity is induced during methylation
      of thiopurines. 1. Purine synthesis de novo is inhibited during formation of me-t
      IMP. Inhibition of PDNS results in depletion of purine nucleotides, with
      subsequently diminishing DNA and RNA synthesis. 2. The increased PRPP levels,
      induced by me-T-IMP, induce increased pyrimidine biosynthesis and cause an
      imbalance in purine nucleotides. This imbalance may lead to inhibition of cell
      growth and after prolonged exposure, to cell death. 3. The observed depletion of
      SAM and the decrease of the SAM/SAH ratio may be an additional mechanism by which
      6MP and me-MPR exert their effects on cell growth and cell viability. Changes in
      SAM/SAH ratio may directly influence methylation reactions. The significant
      decrease of DNA methylation by 6MP and me-t-IMP may influence gene regulation and
      tumor progression. Administration of SAM leads to chemoprevention of rat liver
      carcinogenesis, indicating a role of DNA methylation in tumor progression.
      Besides the effects on methylation of DNA, a decrease of SAM/SAH ratio may also
      affect other processes, such as methylation of RNA, proteins and phospholipids,
      thereby disturbing their functionality. In conclusion, decrease of the SAM/SAH
      ratio resulting from treatment with 6MP and me-MPR may exert many effects in
      these cells. This may open a new field of research, possibly contributing to a
      deeper understanding of the complex mechanisms by which 6MP provokes
      cytotoxicity.

PMID- 7572349
TI  - Sorting and budding of constitutive secretory vesicles in hepatocytes and
      hepatoma cells.
AB  - We have isolated a population of post-TGN secretory vesicles from hepatocytes.
      These vesicles of 100-150 nm diameter carry heparan sulfate proteoglycans.
      Secretory proteins (albumin, apo-lipoprotein E, fibrinogen) are sorted into
      different post-TGN secretory vesicles. A member of the ARF family of small GTP
      binding proteins is associated with these vesicles. A unique peripheral membrane
      protein of these vesicles (VAPP14) was shown to exist also on the TGN. Brefeldin
      A leads to a dissociation of VAPP14 from the TGN. Antibodies against VAPP14
      inhibit budding of proteoglycan containing vesicles from the TGN in a cell-free
      system. Inhibition occurred also in the presence of GTP-gamma-S. The same type of
      vesicles exists in H35 Reuber hepatoma cells.

PMID- 7572350
TI  - Matrix metalloproteinase inhibitors: a novel class of anticancer agents.
AB  - Matrix metalloproteinase inhibitors represent a new therapeutic approach to the
      treatment of advanced cancer. These inhibitors block the activity of proteolytic
      enzymes, matrix metalloproteinases, used by tumor cells to break down and remodel
      tissue matrices during the process of metastatic spread. As such they were
      regarded initially as inhibitors of metastasis. However, recent studies have
      shown that these inhibitors can also act to inhibit tumor growth by (i)
      preventing local invasion and promoting stromal encapsulation and (ii) by
      inhibiting tumor neovascularization. Matrix metalloproteinase inhibitors
      therefore have the potential to halt tumor progression and it is possible to
      envision their use as a low toxicity complement to cytotoxic therapies.
      Batimastat (BB-94) is the first inhibitor of this class to enter clinical trial
      in cancer patients. In a phase I/II trial in patients with malignant ascites
      batimastat was well tolerated and there were preliminary signs of efficacy.

PMID- 7572351
TI  - Compartmentalization of cyclic AMP phosphodiesterases, signalling 'crosstalk',
      desensitization and the phosphorylation of Gi-2 add cell specific personalization
      to the control of the levels of the second messenger cyclic AMP.

PMID- 7572352
TI  - Regulation of c-myb expression in ML-1 human myeloblastic leukemia cells by c-ets
      1 protein.
AB  - C-myb and c-ets-1 have variously been demonstrated to function as protooncogenes.
      Using a human leukemic cell line, ML-1, we have examined the mechanism by which
      these genes participate in establishing the sustained proliferation mode that is
      characteristic of the transformed cell. In the absence of serum, ML-1 cells were
      found to require IGF-1 and transferrin (TF) for growth and TGF-beta or TNF-alpha
      plus TF for differentiation. Upon administration of the growth factors, c-myb
      expression increased within 60 min, whereas after addition of the differentiation
      factors c-myb expression ceased completely within 3 hr. A correlation was found
      to exist between the level of c-ets-1 protein in the cells, the extent to which
      that protein is bound to intron I of the myb gene and the amount of c-myb mRNA
      that is expressed. Upon administration of growth factors, a sizable increase in
      the intracellular, and particularly, in the intranuclear level of c-ets-1 protein
      was observed, whereas a pronounced decrease in the level of this protein occurred
      after exposure to the differentiation factors. These data demonstrated that the
      level at which an oncogene-specified transcription factor is expressed can affect
      the expression of other target oncogenes involved in the regulation of cell
      proliferation. Stimulated expression of such transcription factor can then lead
      to the continuous proliferation cycle characteristic of the cancer cell.

PMID- 7572353
TI  - Isolation and biological activities of signal transduction inhibitors from
      microorganisms and plants.
AB  - Microorganisms and plants are treasuries of secondary metabolites having unique
      structures and biological activities. We have isolated inhibitors of cellular
      signal transduction from them. Phosphatidylinositol turnover inhibitors include
      inostamycin, piericidins and echiguanines. Erbstatin and lavendustin A were
      isolated as tyrosine kinase inhibitors, and dephostatin was isolated as a
      tyrosine phosphatase inhibitor. Recently, we have isolated a new vinca alkaloid
      having anti-ras activity. These signal transduction inhibitors will be useful for
      mechanistic studies and suppression of cancer.

PMID- 7572354
TI  - Structure-function relationships for a new series of pyridine-2-carboxaldehyde
      thiosemicarbazones on ribonucleotide reductase activity and tumor cell growth in
      culture and in vivo.
AB  - The synthesis of a new series of pyridine-2-carboxaldehyde thiosemicarbazones
      (HCTs) that have amino groups in the 3- and 5-positions has allowed the
      comparison of the structure/function relationships with regard to inhibition of
      ribonucleotide reductase activity, L1210 cell growth in culture and L1210
      leukemia in vivo. 3-Aminopyridine-2-carboxaldehyde thiosemicarbazones are more
      active than the corresponding 3-hydroxy-derivatives. The 3-amino-2-pyridine
      carboxaldehyde thiosemicarbazones were also more active then the 5-amino-2
      carboxaldehyde thiosemicarbazones in inhibiting ribonucleotide reductase activity
      and L1210 cell growth in culture and in vivo. N-Acetylation of the 3-amino
      derivative resulted in a compound that was much less active both in vitro and in
      vivo; N-acetylation of the 5-amino derivative did not alter the in vitro
      inhibitory properties, but did eliminate the antitumor properties in vivo. When
      the most active HCTs were studied in more detail, it was found that the
      incorporation of [3H]thymidine into DNA was inhibited completely without the
      inhibition of [3H]uridine incorporation into RNA. Further, the conversion of
      [14C]cytidine to deoxycytidine nucleotides and incorporation into DNA was
      inhibited by the HCTs without an effect on the incorporation of cytidine into
      RNA. These data support the conclusion that ribonucleotide reductase is the major
      site of action of these HCTs. The 3-aminopyridine-2-carboxaldehyde
      thiosemicarbazones emerge as strong candidates for development for clinical
      trials in cancer patients.

PMID- 7572357
TI  - Overview: cheese chemistry and rheology.

PMID- 7572355
TI  - Human thymidine kinase 1. Regulation in normal and malignant cells.
AB  - In mammalian cells, salvage pathway phosphorylation of thymidine is catalyzed by
      two thymidine kinases: the cell-cycle regulated cytoplasmic TK1 and the
      constitutively expressed mitochondrial TK2. Since TK1 is virtually absent in non
      dividing cells, TK2 is probably the only thymidine kinase present in these cells.
      In cellular metabolism, TK1 and TK2 presumably serve to maintain sufficient dTTP
      for DNA replication and repair. TK1 purified from phytohemagglutinin-stimulated
      human lymphocytes is a dimer in the absence and a tetramer in the presence of
      ATP. In addition to the molecular weight transition, incubation with ATP at 4
      degrees C or storage with ATP induces a reversible, enzyme concentration
      dependent, kinetically slow transition from a low to a high affinity form of TK1,
      with Km values of 14 microM and 0.5 microM, respectively. This affinity
      difference implies that at cellular thymidine concentrations, the difference in
      catalytic activity between the two TK1 forms will be 3-5-fold. Calculations of
      cellular TK1 concentration suggested that the low affinity dimer form was
      dominant in G0/G1 cells and the high affinity tetramer form in S-phase cells.
      Hence, the transition may serve to fine-tune the cell-cycle regulation of
      thymidine kinase activity on the post-translational level. To study the ATP
      effect on the molecular level, an IPTG inducible T7 RNA polymerase-dependent
      expression system for the entire human TK1 polypeptide in E. coli was
      established. The recombinant TK1 has the same subunit mass and specific activity
      as the native enzyme. However, the recombinant TK1 solely displayed the kinetics
      of the high affinity form, with Km values of 0.3-0.4 microM regardless of pre
      exposure to ATP, indicating that the ATP effect may be dependent on post
      translational modifications absent in E. coli. Surprisingly, we did not observe
      any effect of ATP on TK1 purified from bone-marrow cells from a patient with
      acute monocytic leukemia (AMOL). Furthermore, the Km values of TK1 from these
      cells were 45 microM for the ATP-free enzyme and 65 microM for the ATP-incubated
      enzyme. With TK1 purified from HL-60 cells, we obtained the same pattern and
      kinetic values as for TK1 from lymphocytes. In the light of the results with the
      recombinant TK1, we presume that the lack of ATP effect and very high Km values
      observed for the AMOL TK1 may be due to changes in post-translational regulatory
      mechanisms in acute monocytic cells.

PMID- 7572356
TI  - Glucuronidation by human colorectal adenocarcinoma cells as a mechanism of
      resistance to mycophenolic acid.
AB  - Mycophenolic acid (MPA), a potent and specific inhibitor of IMP dehydrogenase,
      exerts its anti-mitotic action by a rapid depletion of the cellular content of
      guanine nucleotides. Although MPA is a potent inhibitor of GTP synthesis in the
      HT29 line of human colorectal adenocarcinoma cells in short-term culture, its
      ability to depress the cloning efficiency of these cells was found to be markedly
      less than against the mouse mammary carcinoma line, EMT6. In vivo, MPA is
      efficiently converted to the biologically inactive O-glucuronide derivative
      thereby limiting its effectiveness as an anti-tumor agent. Investigation of the
      fate of MPA incubated with monolayer cultures of HT29 and EMT6 cells revealed
      that the compound is rapidly converted to the O-glucuronide derivative by HT29
      cells, but not by EMT6 cells. Confirmation of the identity of the glucuronide
      formed by HT29 cells was obtained by its conversion to MPA after incubation with
      beta-glucuronidase and by comparison of the mass spectrum of its HPLC peak with
      that of synthetic MPA O-glucuronide. Cultures of two other lines of human
      colorectal adenocarcinoma cells, Colo-205 and LoVo, also depleted their culture
      media of MPA although we have not yet established whether these cells also
      synthesize the glucuronide. The intrinsic partial resistance of HT29 cells to MPA
      appears to be associated with the ability of these cells to convert MPA to the
      biologically inactive glucuronide. These results, in conjunction with other
      reports of the capacity of colorectal cancer cells for Phase I and II metabolism
      of xenobiotics, may have implications for the design of drugs intended for the
      treatment of colorectal cancer.

PMID- 7572359
TI  - Time-temperature effects on microbial, chemical and sensory changes during
      cooling and aging of cheddar cheese.

PMID- 7572358
TI  - Assessment of accelerated cheese ripening by reverse-phase HPLC.

PMID- 7572360
TI  - Methods for assessing proteolysis in cheese during maturation.

PMID- 7572361
TI  - Contribution of milk-clotting enzymes and plasmin to cheese ripening.

PMID- 7572362
TI  - Contribution of lactic acid bacteria to cheese ripening.

PMID- 7572363
TI  - Rheology of reduced-fat cheese containing a fat substitute.

PMID- 7572364
TI  - Maturation profiles of cheddar-type cheese produced from high heat treatment milk
      to incorporate whey protein.

PMID- 7572365
TI  - Inhibition of proteolysis in mozzarella cheese prepared from homogenized milk.

PMID- 7572366
TI  - Practical aspects of electron microscopy in cheese research.

PMID- 7572367
TI  - Factors affecting the functional characteristics of unmelted and melted
      mozzarella cheese.

PMID- 7572368
TI  - Immunolocalization and microstructure of milk proteins and fat mimetics in
      reduced fat cheese.

PMID- 7572369
TI  - Microstructure studies of reduced-fat cheese containing fat substitute.

PMID- 7572370
TI  - Influence of casein peptide conformations on textural properties of cheese.

PMID- 7572372
TI  - Applications of confocal microscopy to fat globule structure in cheese.

PMID- 7572371
TI  - Electron-density patterns in low-fat mozzarella cheeses during refrigerated
      storage.

PMID- 7572373
TI  - Technology of manufacturing reduced-fat cheddar cheese.

PMID- 7572374
TI  - Nutritional aspects of reduced-fat cheese.

PMID- 7572376
TI  - Whey proteins in cheese--an overview.

PMID- 7572375
TI  - Microbiology and biochemistry of reduced-fat cheese.

PMID- 7572377
TI  - Reduced-fat cheese: regulations and definitions.

PMID- 7572378
TI  - Improving the sensory characteristics of reduced-fat cheese.

PMID- 7572379
TI  - Chemical species in cheese and their origin in milk components.
AB  - Cheese making is the process of concentrating milk fat and protein by separation
      from water and soluble components. The objective of the cheese maker is to
      maximize yield efficiency by optimum utilization of each milk component while not
      compromising cheese quality. Cheese yielding potential of milk may be increased
      by selective breeding for specific protein genotypes, especially the BB variant
      of both kappa-casein and beta-lactoglobulin. Milk fat is included in cheese by
      occlusion into the protein coagulum. Participation of casein in both lactic and
      rennet coagulation is nearly complete so that casein losses to the whey occur
      mainly during cutting and the early stages of cooking. In lactic cheese,
      excepting cottage cheese, it is possible to eliminate losses of fines by
      centrifugal or membrane separation of curd. In heat-acid precipitated varieties
      protein recovery is increased by inclusion of whey proteins but fat recovery is
      very dependent on coagulation conditions. In ripened cheese obtaining the correct
      basic structure and composition is critical to texture and flavour development
      during curing.

PMID- 7572380
TI  - Biogenesis of flavour compounds in cheese.

PMID- 7572381
TI  - Rheology of reduced-fat mozzarella cheese.

PMID- 7572382
TI  - Cheddar cheese flavour and chemical indices: changes during maturation.

PMID- 7572383
TI  - CD4+ and CD8+ T lymphocyte activation in HIV infection. Implications for immune
      pathogenesis and therapy.

PMID- 7572385
TI  - Programmed death of T cells in the course of HIV infection.

PMID- 7572384
TI  - Mechanism of apoptosis in peripheral blood mononuclear cells of HIV-infected
      patients.
AB  - Lymphocytes from patients with HIV-infection have been shown to undergo
      accelerated spontaneous apoptosis. Binding of CD4 molecules by HIV envelope
      protein gp120 and anti-gp120 antibodies can lead to crosslinking of CD4 molecules
      (CD4XL) in vitro and conceivably in vivo. We have recently shown that CD4XL in
      vitro, when performed in unfractioned peripheral blood mononuclear cells (PBMC)
      on normal HIV seronegative donors, is by itself sufficient to induce T cell
      apoptosis (Blood 82:3392, 1993). To further examine the mechanisms involved in
      apoptosis, we have examined the expression of Fas antigen (Fas) using 3 color
      flow cytometry. Fas is a cell surface molecule known to mediate apoptosis
      triggering signals. We induced CD4XL in PBMC obtained from normal donors, either
      by anti-CD4 mAb Leu3a or by HIV-1 envelope protein gp160. PBMC subpopulations
      were examined for Fas Ag expression and for apoptosis induction by flow
      cytometry. CD4XL was found to result in increased Fas expression as well as Fas
      mRNA in lymphocytes and the up-regulated Fas Ag was closely correlated with
      apoptotic cell death. CD4XL in PBMC also resulted in induction of the cytokines
      INF-tau and TNF-alpha in the absence of IL-2 and IL-4 secretion. Both these
      cytokins contributed to Fas Ag up-regulation and antibodies to TNF-alpha and INF
      tau abrogated CD4XL-induced Fas up-regulation and T-cell apoptosis. These
      findings suggest that CD4XL occurring in vivo might play an important role in
      inducing an abberant cytokine profile (which has been observed in HIV infected
      individuals) and also in triggering of T-cell apoptosis.

PMID- 7572386
TI  - T cell apoptosis as a consequence of chronic activation of the immune system in
      HIV infection.

PMID- 7572387
TI  - Apoptosis during HIV infection. A cytopathic effect of HIV or an important host
      defense mechanism against viruses in general?

PMID- 7572388
TI  - From cell activation to cell depletion. The programmed cell death hypothesis of
      AIDS pathogenesis.

PMID- 7572389
TI  - Immunosuppression by a noncytolytic virus via T cell mediated immunopathology.
      Implication for AIDS.
AB  - HIV is basically a non- or poorly cytocidal virus. Therefore, HIV infections in
      humans represent an apparent perversity in the balance between the host immune
      system and infectious agent: This noncytopathic virus infects macrophages,
      antigen presenting cells, helper T cells and other host cells which are then
      destroyed by the CD8+ T cell immune response. Thus, HIV infects some of the key
      cells involved in immune reactions and therefore induces the immune system to
      destroy itself and thereby enables the virus to persist. Accordingly,
      immunosuppression is not a cause of HIV cytopathogenicity but a consequence of
      conventional T cell mediated immunopathology that destroys macrophages antigen
      presenting cells, T helper cells and facilitates infection by trivial
      intracellular parasites which eventually cause fatal disease. This
      immunopathological view of AIDS is testable and, if correct, impinges on
      rationales for AIDS prevention and treatment.

PMID- 7572390
TI  - Markers of immune cell activation and disease progression. Cell activation in HIV
      disease.
AB  - Immune cell activation is a feature of infection with the human immunodeficiency
      virus (HIV). Here we report our studies on a cohort of over 400 patients with HIV
      infection studied cross-sectionally and longitudinally to examine the
      relationship between markers of immune cell activation and disease progression.
      To examine disease progression, 340 patients with HIV infection but without AIDS
      were followed for a total of 574 patient years, during which 56 developed AIDS.
      In our first study, 157 patients in CDC groups II-IV were examined cross
      sectionally for in vivo expression of the activation markers HLA-DR and CD25 on
      CD3, CD4 and CD8 T cells. Levels of CD3+ HLA-DR+ T cells are high in HIV
      infection and show a significant negative correlation with CD4 counts (r = 0.52;
      p < 0.001). The appearance of HLA-DR+ CD3+ T cells is an early feature of
      asymptomatic HIV+ patients, with a greater proportion (82%) showing abnormally
      high levels of these than abnormally low levels of CD4 (52%; p < 0.001).
      Examining activation of the CD4 subset specifically is likely to be of greater
      interest, given that this cell is the viral target. Indeed, we found that in the
      cross-sectional study, levels of HLA-DR+ and CD25+ CD4 lymphocytes show a step
      wise linear increase with increasing disease severity (significant test for
      linear trend; p < 0.001). In our previous studies, only declining CD4 count has
      shown such a significant linear trend. These data suggest that measuring
      activated CD4+ T cells in the periphery may be a powerful predictive tool. In our
      second study, we examined the expression of other markers acquired (CD45R0) and
      lost (CD45RA) following activation of naive T cells. Examining expression of
      these on CD4 and CD8 cells cross-sectionally in 71 HIV+ patients, we found
      abnormalities in percentage levels of CD45RA+ and CD45R0+ populations, none of
      which showed any relationship to disease severity. Intriguingly, however, we
      noted that the surface density of both CD45RA and CD45R0 molecules on CD4 and CD8
      cells was markedly and significantly reduced at all stages of HIV infection (eg
      relative specific fluorescence reduced by up to 50%; p < 0.001). This abnormality
      was confirmed in studies using antibodies to a common epitope on all CD45
      isoforms (pan-CD45) and to the CD45RB isoform. Finally, returning to the question
      of immune cell markers of activation and disease progression, we have examined
      some of the best documented markers in our longitudinal study.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7572392
TI  - Autoimmunity, apoptosis defects and retroviruses.
AB  - Autoimmunity and AIDS both share the common feature of increased expression of
      retroviral protein products and abnormal apoptosis of immune cells (81). This
      leads to a more global immunomodulatory defect (82-84). The challenge in the
      future will be to devise compounds that can either regulate the effect of the
      retroviral products on apoptosis, or that can inhibit apoptosis pathways in order
      to restore normal immune system function.

PMID- 7572391
TI  - Clonal expansion of T cells and HIV genotypes in microdissected splenic white
      pulps indicates viral replication in situ and infiltration of HIV-specific
      cytotoxic T lymphocytes.
AB  - Human immunodeficiency virus (HIV) replication and T cell proliferation was
      investigated in situ by a PCR based analysis of individual microdissected splenic
      white pulps. Founder effects, revealed by an exquisite compartmentalization of
      HIV genotypes and T cells, indicated the recruitment of latently infected CD4+ T
      cells through highly localized antigen presentation, rather than the infection of
      CD4+ T lymphoblasts by blood borne virus or immune complexes. HIV infected white
      pulps could be infiltrated by HIV specific cytotoxic T lymphocytes, so
      implicating them in CD4+ T cell destruction in vivo. Together these data describe
      an iterative and deleterious mechanism of antigen driven T cell recruitment and
      activation, HIV replication and spread, with consequent destruction of the newly
      infected cells.

PMID- 7572393
TI  - AIDS as immune system activation. Key questions that remain.
AB  - Immune system activation is gaining attention as a central part of HIV
      pathogenesis. Although there is no consensus yet as to the source of the signal
      or the result of the signalling, this line of thinking represents a significant
      shift in the paradigm away from considering HIV disease like any other cytopathic
      viral infection. Hopefully, completion of studies focussed on this approach will
      lead to more complete understanding of AIDS and more effective therapies, and
      will at least bring to the fore some of the central unanswered questions in
      modern cellular immunology.

PMID- 7572394
TI  - Inhibition of T lymphocyte activation and apoptotic cell death by cyclosporin A
      and tacrolimus (FK506). Its relevance to therapy of HIV infection.
AB  - Theoretically, drugs that inhibit programmed cell death could be used to inhibit
      the increased apoptotic decay of lymphocyte populations in human immunodeficiency
      virus (HIV) infection. The concept that immunopathologic processes cause immune
      suppression provides a further rationale for the use of agents such as
      cyclosporin A (CsA) or tacrolimus (formerly known as FK506) early in HIV
      infection to reduce cytotoxic CD8+ T cell-mediated destruction of HIV-infected
      target cells.

PMID- 7572395
TI  - Cyclophilin and gag in HIV-1 replication and pathogenesis.

PMID- 7572396
TI  - Long-term follow-up of HIV positive asymptomatic patients having received
      cyclosporin A.
AB  - The data of the 27 asymptomatic HIV-1 seropositive patients with CD4+ cell count
      between 300 and 600/microliters treated by Cyclosporin A (CSA) (7.5 mg/kg/day) in
      our institution between October 1985 and 1987 were reviewed in October 1993.
      Hemoglobin concentration, platelet count, total lymphocytes, CD4+ and CD8+ cell
      counts and serum core protein p24 antigenemia, as well as creatininemia measured
      before CSA onset, at CSA cessation and twice a year were recorded as well as
      clinical signs and CSA toxicities. In October 1993 median duration of CSA
      treatment was 11 months, median follow-up after CSA cessation was 45 months and
      median total follow-up was 67 months. Toxicities of CSA were those commonly
      encountered in other pathologies. Under CSA no patient progressed toward clinical
      AIDS (1987 definition). The mean CD4+ cell count of the 27 patients remained
      unchanged (gain of 1 cell/year) under CSA treatment, while it decreased at a rate
      of 50 cells/year after CSA cessation (p < 0,005). On the other hand CSA treatment
      had no significant impact on the evolution of total lymphocyte count, CD8+ cell
      counts, and P24 antigenemia.

PMID- 7572397
TI  - Prospective views of HIV pathology. Clues for therapeutic strategies.

PMID- 7572398
TI  - The role of the cell cycle in HIV-1 infection.
AB  - Infection of quiescent lymphocytes with human immunodeficiency virus type 1 (HIV
      1) does not result in production of progeny virus. We have previously reported
      that although HIV-1 can enter quiescent lymphocytes with high efficiency, the
      reverse transcription process does not go to completion. This results in a viral
      genome which is composed partly of viral RNA and partly of viral DNA. If a
      mitogenic signal is applied shortly after infection to a cell harboring such a
      structure, reverse transcription can go to completion and progeny virus will be
      produced. However, this partially reverse transcribed structure is extremely
      labile, and the efficiency of virus rescue decreases rapidly, with increasing
      times between infection and activation. Our laboratory is using inhibitors of
      cell activation to identify at which stage of the cell cycle this block to
      reverse transcription occurs. We have found that agents that arrest the cell in
      the late G1 phase of the cell cycle do not alter the ability of the virus to
      complete reverse transcription. However, agents that inhibit activation of the
      cell by blocking transition through G1 prevent completion of reverse
      transcription. It thus appears that immunosuppression of the target cell may be a
      means of preventing productive infection of the cell. We have also been using the
      severe combined immunodeficient mouse implanted with human tissue (SCID-hu) as an
      in vivo model to study HIV-1 pathogenic properties. When human fetal thymic
      implants in these animals are infected by HIV-1, profound depletion of CD4
      bearing human thymocytes is seen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572400
TI  - Regulation of macrophage activation and HIV replication.

PMID- 7572399
TI  - Molecular basis of cell cycle dependent HIV-1 replication. Implications for
      control of virus burden.
AB  - Research is beginning to yield insight into determinants which govern cell cycle
      dependence of provirus establishment by the onco-retroviruses. In the case of HIV
      1, nucleophilic components associated with the viral preintegration complex
      facilitate mitosis independent nuclear localization of viral DNA and provirus
      establishment. Differences in the metabolic activity between G0 T cells and
      macrophages, the two primary targets for HIV-1 infection, lead to significantly
      different outcomes with regards to provirus establishment following infection of
      these cells. Thus, macrophages appear fully permissive to productive HIV-1
      replication while non-dividing (G0 T cells) restrict virus replication at a step
      which proceeds nuclear import of viral DNA. The requirement for T cell activation
      in productive HIV-1 replication has important implications for the relationship
      between immune activation and virus burden. It remains to be determined whether
      modulating the immune activation status of the infected individual may provide an
      opportunity for modulating virus burden and influencing disease course.

PMID- 7572401
TI  - Investigations on autologous T-cells for adoptive immunotherapy of AIDS.
AB  - We report on the preclinical results of an immunotherapeutic approach of AIDS
      mediated by ex vivo propagated CD4+ and CD8+ T-cells. A mean yield of 6.23 x
      10(9) lymphocytes, containing 1.82 x 10(9) CD4+, 3.23 x 10(9) CD8+ T-lymphocytes
      and 8.39 x 10(6) CD34+ peripheral blood progenitor cells (PBPC) were be obtained
      by continuous flow cytapheresis (CFC) in 15 asymptomatic HIV infected patients
      (CD4-count > 350/mm3). The CD4/CD8 ratio (mean: 0.53, SD: +/- 0.15) in the cell
      concentrates reflected the distribution of the circulating lymphocyte subsets in
      vivo. Absolute lymphocyte counts decreased at a mean of 404/microliter (25%)
      immediately after CFC but were replaced from the extravascular pool within one
      hour. Neither the CD4/CD8 ratio nor p24-antigen and neopterin levels did change
      significantly after cell separation. No alteration of the number of proviral DNA
      copies (1/10(3)-1/10(6)) could be detected in peripheral T-helper cells by
      semiquantitative PCR after lymphapheresis. Cells were cryopreserved in liquid
      nitrogen without substantial loss of viability or function. Ex vivo propagation
      of T-cells in a strictly autologous manner in the presence of PHA + IL-2 for 14d
      resulted in a 50-fold expansion rate (140-fold in healthy controls, p < 0.001).
      Viral replication could be controlled but not completely eliminated by
      cocultivation with autologous CD8+ T-lymphocytes as measured by limiting dilution
      nested PCR (NPCR). The expanded cells showed the typical phenotype of highly
      activated memory type T-lymphocytes (CD3+ CD45RO+ CD25+ HLA-DR+). The
      distribution of CD4+ and CD8+ T-cells did not reveal significant changes before
      and after culture indicating that both subsets were equally expanded.
      Functionally important membrane or intracellular epitopes which were found to be
      decreased in HIV infected subjects (CD7, CD55, CD59) before culture were
      reconstituted after ex vivo propagation of T-cells. The functional importance of
      the up-regulation of complement regulating epitopes (CD55, CD59) after culture
      could be proven by a significant inhibition of cytolysis of T-cells in the
      presence of autologous complement. The majority (75%) of expanded CD8+ T-cells
      stained positive with mAb TIA-1 which is directed to intracellular granules
      within cytotoxic T-cells. Furthermore, programmed cell death of expanded T-cells
      could be prevented by cocultivation with fibroblasts which are believed to
      secrete a cytokine pattern preventing activated T-cells from apoptosis after
      withdrawal of IL-2 and other stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572402
TI  - Rational problems associated with the development of cellular approaches in
      controlling HIV spread.

PMID- 7572403
TI  - The role of surface CD4 in HIV-induced apoptosis.

PMID- 7572405
TI  - Renal involvement in type II diabetes.

PMID- 7572404
TI  - Hepatitis C virus infection, cryoglobulinemia, and glomerulonephritis.

PMID- 7572406
TI  - The natural history of renal disease in non-insulin-dependent diabetes mellitus:
      lessons from the Pima Indians.

PMID- 7572407
TI  - Genetics of non-insulin-dependent diabetes mellitus: from genes to the disease.

PMID- 7572408
TI  - Inhibitors of crystallization.

PMID- 7572410
TI  - Nutritional determinants of nephrolithiasis.

PMID- 7572409
TI  - Leukotrienes and 15-lipoxygenase products in glomerulonephritis.
AB  - In Figure 2, a schematic summary of current evidence implicates 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. In this review, we have presented evidence for the pathophysiologic
      relevance of leukotrienes in glomerular immune injury and the emerging data on
      the multifaceted, counter-inflammatory 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, whether they be 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 toward the attainment
      of a highly worthwhile goal--the cure of glomerulonephritis.

PMID- 7572411
TI  - Primary hyperoxaluria type 1: the therapeutic dilemma.

PMID- 7572412
TI  - Muscular function in chronic renal failure.

PMID- 7572413
TI  - Extracorporeal treatment of acute renal failure: methods, indications, quantified
      and personalized therapeutic approach.

PMID- 7572415
TI  - Hepatitis C virus infection in hemodialyzed patients and kidney allograft
      recipients.

PMID- 7572414
TI  - Role of nitric oxide in glomerular physiology and pathophysiology.

PMID- 7572416
TI  - Growth factors and the glomerulus: relationships between development and injury.

PMID- 7572417
TI  - Genetic engineering of the donor species to control hyperacute xenograft
      rejection.

PMID- 7572419
TI  - Renal involvement in type I glycogen storage disease.

PMID- 7572420
TI  - Kidney involvement in mitochondrial disorders.

PMID- 7572418
TI  - The dichotomous functions of passenger leukocytes in solid-organ transplantation.

PMID- 7572421
TI  - Toward the identification of a gene for familial juvenile nephronophthisis
      (autosomal recessive medullary cystic kidney disease).

PMID- 7572422
TI  - Involvement of tumor necrosis factor-alpha in the pathogenesis of experimental
      and human glomerulonephritis.
AB  - The evidence supporting a role for TNF-alpha in glomerular diseases can be
      summarized with the following: TNF-alpha can be secreted in the kidney by
      intrinsic renal cells and infiltrating phagocytes, as has been shown in vitro and
      in vivo during glomerular injury. TNF-alpha has proinflammatory actions which
      include cell death, chemotactic properties, and modulation of secretion of other
      inflammatory mediators, and extracellular matrix (Fig 5). Administration of
      exogenous TNF-alpha or agents that induce release of endogenous TNF alpha, such
      as endotoxin, increase the severity of experimental glomerular injury.
      Furthermore, the blockade of TNF-alpha action with specific antibodies, soluble
      receptors, or inhibitors improves the outcome of glomerulonephritis. Finally,
      several of the agents currently in use for the therapy of glomerular injury, such
      as corticosteroids and cyclosporine, are known to modulate the production of TNF
      alpha. Specific TNF-alpha antagonists or inhibitors may have a role in the
      management of glomerulonephritis in the future.

PMID- 7572423
TI  - Interleukin-10 and its implications for immunopathology.

PMID- 7572424
TI  - Suppression of experimental glomerulonephritis by interference with T- or B-cell
      activation signals or adhesion molecules.

PMID- 7572425
TI  - A highly sensitive and rapid procedure for direct PCR detection of Leishmania
      infantum within human peripheral blood mononuclear cells.
AB  - We have developed a highly sensitive, simple and rapid procedure to detect
      Leishmania infantum within human macrophages. It only requires ficoll preparation
      of peripheral blood mononuclear cells from the patient, and their direct use for
      Leishmania kDNA amplification by polymerase chain reaction. Under these
      conditions, about one parasite can be detected in a one million human cell
      environment. Results, including those of a hybridization step to confirm the
      diagnosis specificity, are obtained with 24 h, a very short period as compared to
      current diagnostic methods. This procedure is of particular interest for early
      detection and early drug treatment of leishmaniasis, especially in the case of
      HIV coinfection. Furthermore, the method could be useful for monitoring the
      efficiency of new leishmaniasis treatments in infected patients.

PMID- 7572426
TI  - Desirable characteristics of a schistosomiasis vaccine: some implications of a
      cost-effectiveness analysis.
AB  - This paper investigates some of the characteristics which a vaccine for
      schistosomiasis would require to be more cost-effective than chemotherapy. The
      impact of a variety of possible vaccination scenarios are assessed in terms of
      the discounted years of heavy infection prevented in children, and the cost
      effectiveness of these approaches are compared with annual mass treatment. The
      analyses demonstrate that the three critical parameters determining whether a
      vaccine would ever be more cost-effective than mass chemotherapy are price,
      duration of protection and efficacy. If the vaccine had sufficient duration of
      protection to be delivered through the regular childhood immunization programmes
      (EPI), it could be more cost-effective than annual chemotherapy. The necessary
      condition is that adding the vaccine to EPI must not cost more than $4.30 per
      person in excess of one round of chemotherapy. For a shorter duration of vaccine
      protection, the schistosomiasis vaccine could not exceed the cost (including
      delivery costs) of one round of annual chemotherapy by more than approximately
      $3.50.

PMID- 7572427
TI  - The 1990 meningococcal meningitis epidemic of Sarh (Chad): how useful was an
      earlier mass vaccination?
AB  - A large outbreak of meningococcal meningitis (Serogroup A) occurred in southern
      Chad in 1990. We describe the epidemic in the town of Sarh, where a mass
      vaccination against meningococcal meningitis had taken place two years before, in
      1988 (estimated coverage: 66%). Early warning that an epidemic was imminent was
      given at the end of February, following more than 15 recorded cases per 100,000
      population on 3 consecutive weeks. This threshold proved to be adequate to
      predict the outbreak. A total of 721 cases were recorded at Sarh hospital and at
      a nearby health centre. Direct agglutination tests confirmed that Neisseria
      meningitis serogroup A was the only causative agent. The overall incidence rate
      in this population of 80,000 was 0.9%. The highest weekly incidence rate was 186
      cases per 100,000 population. The mean age of the patients was 12.6 years and age
      specific incidence rates ranged from 0.23% to 1.42%. The male/female sex ratio
      was 1.36. Overall, the mortality among hospitalized patients was 7.9%. Mortality
      increased during the epidemic. The major risk factor for dying was the delay
      until reaching hospital. Only 4 out of 29 interviewed parents said that their
      child had been vaccinated two years before. Among adult patients this proportion
      was 12/38 (32%). Because of the small numbers and because of the impossibility to
      check the vaccination records it was not possible to assess precisely the impact
      of earlier mass vaccination. However, the previous mass vaccination did not
      prevent this major epidemic and its impact is likely to have been unimportant.

PMID- 7572428
TI  - Optimization of the Magnetic Bead Antigen Capture Enzyme Immuno Assay for the
      detection of circulating anodic antigens in mixed Schistosoma infections.
AB  - In the present study, simplification and adaptation of the Magnetic Bead Antigen
      Capture Enzyme Immuno Assay (MBAC-EIA) technique for detection of circulating
      anodic antigens (CAA) under field conditions was achieved. It was shown that the
      assay could be performed successfully within the broad temperature range of 18-37
      degrees C. The slightly lower sensitivity observed at low temperatures could be
      adjusted for by prolonging the incubation period. Shaking the plate by hand was
      as good as automatic mechanical shaking, aspiration of the supernatant before the
      addition of conjugate was not necessary, and the use of whole blood and serum
      offered similar assay sensitivity. Furthermore incubation times could be
      considerably shortened without loss of sensitivity. A major advantage of the MBAC
      EIA was that the beads, after elution of bound components, were found to be
      reusable. The study also showed that the sensitivity of the MBAC-EIA technique in
      diagnosis of schistosomiasis in a Zimbabwean community endemic for both urinary
      and intestinal schistosomiasis, was 94%.

PMID- 7572429
TI  - The incorporation of N,N'-bis(2,3-dihydroxybenzoyl)-1,6 diazahexane or octane as
      the ligands of spiroarsoranes: their effect on trypanocidal activity.

PMID- 7572430
TI  - Leishmania aethiopica: experimental infections in non-human primates.
AB  - Six Cercopithecus aethiops monkeys, 4 Theropithecus gelada baboons and 2 Papio
      anubis baboons were infected using Leishmania aethiopica isolates originating
      either from localized (LCL) or diffuse (DCL) cutaneous leishmaniasis patients.
      The history of lesions in 4 C. aethiops monkeys infected by LCL strains mimicked
      the process in human LCL patients. Infection of 2 C. aethiops monkeys using a DCL
      strain resulted in localized, non-ulcerative, self-healing nodular lesions. Such
      lesions were also observed in 2 T. gelada baboons infected by LCL strains. Active
      lesions and healing in C. aethiops and T. gelada, after infection by LCL stains,
      were accompanied by positive DTH and immunity to challenge by LCL or DCL strains.

PMID- 7572431
TI  - Urbanization and establishment of Culex quinquefasciatus in a west African rural
      area.

PMID- 7572432
TI  - Trypanosoma brucei rhodesiense: variation in human serum resistance after
      transmission between bushbuck and domestic ruminants by Glossina morsitans
      morsitans.

PMID- 7572433
TI  - Glutathione S-transferase (GST) expression in the human hookworm Necator
      americanus: potential roles for excretory-secretory forms of GST.
AB  - The difficulty in demonstrating protective immunity to human gastro-intestinal
      nematodes is thought to be a consequence of the expression of defences by the
      parasites directed against the toxic metabolites of leukocytes produced during
      inflammation (Brophy and Pritchard, 1992a). Parasite glutathione S-transferases
      (GSTs) may provide part of this defence by detoxifying the secondary products of
      lipid peroxidation produced via immune initiated free-radical attack on host or
      parasite membranes (Brophy and Pritchard, 1994; Taylor et al., 1988).
      Neutralisation of parasite immune defence components could tip the molecular
      balance in favour of the immune response during chronic infections. For example,
      GSTs have been extensively investigated from the digenean parasites Schistosoma
      and Fasciola hepatica and provide protection in animal-model systems (Mitchell,
      1988; Wijffels et al., 1991). In contrast, although GSTs have been initially
      characterised in filarial nematodes (Salinas et al., 1994; Leibau et al., 1994;
      Jaffe and Lambert, 1986), there is limited information on GSTs from human gastro
      intestinal nematode parasites. We were particularly interested in analysing the
      products of hookworms for evidence of the presence of excretory-secretory forms
      of this putative immune defence protein.

PMID- 7572434
TI  - [The effect of extracorporeal shock wave lithotripsy on kidney and adjacent
      tissue detected by magnetic resonance imaging].
AB  - Extracorporeal shock wave lithotripsy (ESWL) using YACHIYODA SZI was performed on
      12 patients with renal stones and the effect on the kidney and adjacent tissue
      was evaluated by magnetic resonance imaging (MRI) before and after treatment.
      Some changes were seen in 6 of the 12(50%) patients; perirenal fluid collection
      in 2 of the 12 (16.7%) patients, subcapsular hematoma in 2 of the 12 (16.7%)
      patients, renal enlargement in 5 of the 12 (31.3%) patients, increased signal
      intensity in perirenal tissue in 6 of the 12 (50%) patients, and loss of the
      corticomedullary junction 2 out of 9 patients (22%). These findings indicated
      fewer changes in the kidney after ESWL using YACHIYODA SZI than in the other
      reports. MRI is also concluded to be effective to detect the changes of the
      kidney after ESWL.

PMID- 7572436
TI  - [Clinical study on cerebrovascular diseases after renal transplantation].
AB  - Between October 1975 and December 1994, 131 renal transplants were performed on
      our hospital. Eight of these patients had 9 cerebrovascular diseases, which were
      2 cerebral hemorrhages, 5 cerebral infarctions, 2 subarachnoid hemorrhages. Five
      of the 8 patients whose graft functions were bad died. We studied the
      relationship of the incidence of these complications to some factors as follows;
      1) blood pressure, 2) hypercholestemia, 3) duration of hemodialysis, and 4) graft
      function. The cerebrovascular diseases after renal transplantation were related
      to the hypertension after renal transplantation and no correlation with the other
      factors could be found. Therefore, we think that the control of the hypertension
      after renal transplantation is the most important for the cerebrovascular
      diseases and the patient's prognosis.

PMID- 7572437
TI  - [The clinical usefulness of urinary determinations of cytokeratin 19 fragment
      (CYFRA 21-1) in urothelial tumor].
AB  - The urinary CYFRA 21-1 value corrected for urinary creatinine (ng/ml/creatinine),
      was studied in the urine of patients with urothelial tumors. To examine its
      clinical significance we studied urinary CYFRA 21-1 excretion (ng/ml/creatinine),
      in a total of 22 urine samples from patients with bladder cancer, 7 from patients
      with renal pelvic and ureteral tumor, 6 from patients with urinary infection 6
      from patients with urinary diversion called ileal conduit, and 8 from healthy
      adult men. The excretion of CYFRA 21-1 in urine was determined by two specific
      monoclonal antibodies (Ks 19.1 and BW 19.21). The mean value of urinary CYFRA 21
      1 in healthy adult men was 1.96 +/- 1.33 (mean +/- SD) ng/ml/creatinine. Urinary
      CYFRA 21-1 showed a higher value in the urine of urinary infection and urinary
      diversion. As to bladder cancer, urinary CYFRA 21-1 showed a higher value in a
      larger volume of tumor than in a smaller volume of tumor in transitional cell
      carcinoma regardless of the grade and stage. These findings suggest that urinary
      CYFRA 21-1 may be a non-specific marker in urothelial tumors.

PMID- 7572438
TI  - Scintigraphic detection of xenografted renal tumor by anti-renal cancer
      monoclonal antibody radiolabeled with technetium-99m.
AB  - Accumulation in the tumor of the RCS-1 monoclonal antibody, which recognizes the
      cell surface antigen of renal cancer cells was examined. The antibody purified by
      affinity chromatography (protein-A column) and gel fractionation was labeled with
      technetium-99m (99mTc) by a direct method. High labeling efficiency (> 98%) could
      be routinely obtained. However, the 99mTc labeling of the antibody did not reduce
      the reactivity of the RCS-1 antibody. The labeled antibody was injected into nude
      mice transplanted with human renal and gastric tumors, and the accumulation of
      the antibody in each tumor and various tissues was compared at 48 hours after
      injection. The highest accumulation of radiolabeled RCS-1 antibody was observed
      in the AM-RC-3 renal tumors; at 8.0% of the injected dose per gram and a tumor-to
      blood ratio of 1.05, respectively. However, the radiolabeled RCS-1, did not show
      specific accumulation in the gastric tumor nor in any tissues tested. The
      xenografted tumor, AM-RC-3 was successfully visualized with the radiolabeled RCS
      1 antibody by scintigraphy.

PMID- 7572435
TI  - [Clinical studies of 15 cases of renal angiomyolipoma].
AB  - Fifteen cases of renal angiomyolipoma seen between May, 1988 and October, 1994 in
      our hospital are presented. Surgical treatment was performed in 6 cases, 1 of
      which was falsely diagnosed as liposarcoma by frozen specimen during the
      operation. Nine cases were only followed-up by ultrasonography and/or computed
      tomography. In 2 cases, in which enucleation was performed after a follow-up
      period of more than one year, tumors were inclined to grow rapidly. In 5 cases,
      which were not operated and followed-up for more than one year, tumors were
      inclined to grow very slowly.

PMID- 7572439
TI  - [Two case reports of retroperitoneal leiomyosarcoma].
AB  - Two cases of retroperitoneal leiomyosarcoma are presented. The first case was in
      a 67-year-old female, whose chief complaint of right upper abdominal mass and
      dull pain. The tumor, 13 x 12 x 8 cm in size, developing in the retroperitoneum
      was removed with the right kidney and vena cava. The pathological diagnosis was
      reported as leiomyosarcoma. The second case was in a 62-year-old male, whose
      complaint was left abdominal swelling, also with general fatigue. A large tumor
      mass, invading over all of the left flank organs, was palpable by physical
      examinations, from which the mass was far beyond surgical approach. Needle biopsy
      revealed the pathological finding of leiomyosarcoma. One month later, the patient
      died of cachexia. Review of the literatures for the retroperitoneal
      leiomyosarcoma, revealed only a few cases; 1.7%, of all leiomyosarcoma to date.

PMID- 7572440
TI  - [Nonobstructive urinary tract dilatation due to diabetes insipidus in a patient
      with craniopharyngioma].
AB  - A 46-year-old man who had a history of hypogonadism, bilateral hydronephrosis and
      huge residual urine volume during the past ten years was admitted complaining of
      fever and flank pain. Polyuria which was more than 4 liters per day and inability
      of urine concentration suggested diabetes insipidus. Magnetic resonance imaging
      (MRI) demonstrated a tumor which was compatible with craniopharyngioma. Tumor
      resection and administration of desmopressin improved polyuria and urinary tract
      dilatation with marked reduction of residual urine volume from 400 ml to 20 ml.

PMID- 7572441
TI  - Patent vitelline duct in an adult deceptively appeared to be acquired umbilical
      urachal sinus: a case report.
AB  - Here is presented a surprisingly rare case in a 40-year-old male who had patent
      vitelline duct by nature. However, his congenital disease appeared deceptively to
      be an acquired umbilical urachal sinus on the diagnostic evaluations including
      fistulography before surgery. The diagnosis was definitely confirmed after the
      successful surgical procedure. The principal reason why these diseases were
      indistinguishable was reviewed. The incidence of each disease and incidence of
      association with umbilical fistula in each disease were discussed. With regard to
      these incidences, we compared urachal anomalies with vitelline duct anomalies
      through reference of several literatures. This is the most unique event we have
      ever clinically experienced.

PMID- 7572442
TI  - [Proliferative cystitis forming tumorous lesion: a case report].
AB  - A 66-year-old woman was admitted with asymptomatic macrohematuria. Cystoscopy
      revealed bladder tumor with a diameter of about 1.5 cm and smooth surface.
      Transurethral resection was performed and histological examination showed
      proliferative cystitis, mainly consisting of cystitis glandularis. Proliferative
      cystitis is not so rare, but tumorous formation of it seems to be unusual.

PMID- 7572444
TI  - [High flow priapism following a straddle-injury-induced arteriocavernosal
      fistula: a case report].
AB  - A 26-year-old man with high flow priapism after blunt perineal trauma, is
      described herein. Patient evaluation included intracavernal blood-gasometry,
      cavernography, color flow Doppler sonography. The blood-gasometry showed pH
      7.413, pO2 77.9 mmHg, pCO2 41.0 mmHg, HCO2- 26.1 mmol/L, BE 2.0 mmol/L. By direct
      cavernosography, pooling of contrast agent was seen at the root of the penis.
      Color flow Doppler sonography revealed pulsatile, turbulent flow within left
      corpus cavernosum. Our case was diagnosed as high flow priapism from these
      findings. Detumescence was not achieved by an alpha-adrenergic agent.
      Superselective embolization of the deep artery of the penis with autologous blood
      clot was performed with good results. Our case demonstrates that this procedure
      is a safe and effective therapy for high flow priapism and that erectile function
      can return to normal.

PMID- 7572443
TI  - [Giant schwannoma in the pelvic cavity presenting as renal failure: a case
      report].
AB  - A case of giant schwannoma in the pelvic cavity detected with renal failure is
      reported. A 50-year-old man was referred to another clinic with chief complaints
      of general fatigue and edema of the face and dorsa of the feet. On March the 4th
      1994, he was hospitalized in the clinic because of renal failure. Bilateral
      hydronephrosis and a giant pelvic tumor were found by computed tomography (CT)
      and ultrasonography. Because bilateral percutaneous nephrostomies failed to
      recover his renal function, he was referred to our clinic for the purpose of
      hemodialysis and the further examination of the tumor on March 16, 1994. The
      pelvic angiography showed that the tumor was fed by the vessel from the left
      internal iliac artery. After the chemo-embolization from the feeding artery,
      tumor resection was performed on May 9, 1994. The tumor was 16x13x10 cm in size,
      and 1,110 g in weight. The histological findings of the tumor revealed the mixed
      type schwannoma of Antoni A and B. Six months after the operation, he has had no
      tumor recurrence. This is a rare case of pelvic schwannoma which was detected
      with renal failure. We reviewed and discussed 56 cases of schwannoma in the
      pelvic cavity, including our case, in the Japanese literature.

PMID- 7572447
TI  - Bacterial flora of semen collected from Danish warmblood stallions by artificial
      vagina.
AB  - Semen samples were collected from 21 Danish Warmblood stallions by the Colorado
      artificial vagina (Colorado AV, 14 samples) or by the Missouri artificial vagina
      (Missouri AV, 7 samples). The semen was examined bacteriologically by direct
      plating (DP) on blood agar plates, and by plating of semen swabs stored in
      Stuart's transport media (TM) at 4 degrees C for 1-4 days. No significant
      differences were observed between results obtained by DP and cultures of
      identical TM samples. Of the 21 samples examined, only 1 TM (4.8%) and 2 DP
      samples (9.5%) were sterile, while the rest yielded a predominantly mixed flora
      comprising 1 to 4 bacterial genera. The natural flora was dominated by coagulase
      negative staphylococci (Staphylococcus lentus, S. capitis, S. haemolyticus, S.
      xylosus) (16/21 = 76%), coryneforms (11/21 = 52%) and alpha-hemolytic
      streptococci and lactobacilli (7/21 = 33%). Potential venereal pathogens were
      isolated from 7 stallions (33%). Beta-hemolytic streptococci were found in 4
      stallions used for natural service, whereas Pseudomonas aeruginosa serotype 6 (2
      samples) and Klebsiella pneumoniae subsp. pneumoniae capsule type K5 (1 sample)
      were isolated from 3 stallions used exclusively for artificial insemination. The
      role of the stallion as a carrier of potential venereal pathogens, and the
      artificial vagina as a source of contamination, is discussed in the context of
      mare endometritis.

PMID- 7572445
TI  - [Leiomyosarcoma of the prostate: a case report of remission for 9 years by
      radiotherapy].
AB  - A 68-year-old-man with chief complaints of pollakisuria and lower abdominal
      discomfort was referred to our hospital on September 19, 1983. A
      histopathological study of the transrectal needle biopsy specimens revealed a
      malignant tumor of the prostate with spindle-shaped cells. The patient had been
      considerably improved by radiotherapy. However, 9 years later, the tumor recurred
      and the histopathological study showed the same findings as the initial biopsy
      and furthermore the recurrent tumor was diagnosed as a leiomyosarcoma of the
      prostate by immunohistochemical stain. He was unresponsive to chemotherapy and
      died 11 years after initial diagnosis.

PMID- 7572446
TI  - [Fournier's gangrene in a patient with perirectal abscess: a case report].
AB  - A case of an 81-year-old man with Fournier's gangrene was reported. The patient
      visited our hospital complaining of scrotal swelling and redness. Perirectal
      abscess was found and ultrasound study revealed thickness of scrotal skin and
      normal testes. The patient was immediately treated with antibiotics, incision and
      debridement of the scrotal skin. The lesion healed 8 weeks later.

PMID- 7572448
TI  - Description and analysis of the use of cold harpoons in the Norwegian minke whale
      hunt in the 1981, 1982 and 1983 hunting seasons.
AB  - Until 1984, cold harpoons, i.e. harpoons with no detonating device, were used to
      hunt minke whales in Norway. To investigate the effectiveness of such harpoons
      and compare them with alternatives, data on kills using cold harpoons were
      collected as part of a project dealing with alternative killing techniques for
      whales. Data on 353 whale kills were collected in 1981-83. The criteria used to
      determine the time of death were cessation of flipper movement, that the mandible
      relaxed, or that the whale hung immobile from the harpoon line. These criteria do
      not take into account any movements caused by spinal reflexes. About 17% of the
      animals died instantaneously (< or = 10 s). The median survival time was 570 s.
      Animals died most rapidly if hit in the brain, heart or major blood vessels. If
      only the lungs were injured, minke whales died less rapidly than terrestrial
      mammals. For whales that did not die immediately, shooting range, animal size and
      the angle of the shot all influenced the time to death. The efficiency of cold
      harpoons could be improved, but their use was no longer considered acceptable,
      and they were replaced by harpoons with penthrite grenades in 1984.

PMID- 7572449
TI  - A Norwegian penthrite grenade for minke whales: hunting trials with prototypes
      and results from the hunt in 1984, 1985 and 1986.
AB  - A penthrite grenade to replace cold harpoons in the Norwegian minke whale hunt
      was developed in 1983-1985. Data on survival times for 259 minke whales were
      collected from the trials in the 1984-86 hunting seasons, when 3 different
      prototypes were used. About 45% of the whales were killed instantaneously. The
      median survival time was 72 s. A substantially higher percentage of instantaneous
      deaths was recorded for penthrite grenades than for cold harpoons. The criteria
      for death were cessation of flipper movement, relaxation of the mandible, or
      sinking without any active movement. Some animals dived before the criteria could
      be controlled. If the central nervous system, heart, lungs or main vessels were
      damaged, a high percentage of the animals died instantaneously. In most cases,
      hits and detonations outside the thorax and central nervous system resulted in
      longer survival times than hits in the thorax. Survival time increased with whale
      size and range for animals not killed instantaneously. Marksmanship, technical
      and functional reliability of equipment and hunting techniques were all crucial
      to a good result. Better training of gunners, improved weapons and hunting
      equipment and more rapid reshooting of wounded animals would reduce the
      proportion of long survival times.

PMID- 7572450
TI  - Follicular development and ovulation in sows: effect of hCG and GnRH treatment.
AB  - Follicular growth, chronology of ovulation and embryo morphology were compared in
      sows ovulating spontaneously and sows, in which the ovulation was attempted
      induced by hCG or GnRH. Indwelling catheters were placed on day 1 (weaning = day
      0) in the ear veins of 18 sows, which were then randomly divided into 3 groups: a
      control group (N = 6), a group (N = 6) given 750 iu hCG (Physex) im 76h after
      weaning (hCG group) and a group (N = 6) given 500 micrograms GnRH (Fertagyl) im
      76h (N = 3) or 100h after weaning (N = 3) (GnRH group). Follicular diameter and
      time of ovulation were monitored by ultrasonography every 4h from day 3 until
      ovulation or development of cysts by means of a sector scanner fitted with a
      5.0/7.5 MHz multiangle probe. Heat detection was performed every 8h from day 3
      until ovulation. On day 13, the sows were slaughtered, the number of corpora
      luteae (CL) was counted, and embryos were flushed from the uteri. The control
      group showed clear heat symptoms, and on day 3, the follicles were typically 3-7
      mm and grew up to 7-10 mm over 2 days, where they remained for approximately 24h
      until ovulation took place 41h +/- 9h after first sign of standing heat. The hCG
      group exhibited no signs of heat, and the follicles only reached 5-8 mm in
      diameter at time of ovulation, which occurred 40h +/- 1h after hCG-injection. The
      GnRH group exhibited inconsistent signs of heat, and the follicles reached a
      maximum size of 7-12 mm in diameter where they remained for more than 24h. Only 2
      sows in this group ovulated within 84-92h after the GnRH injection, and
      development of bursa cysts and cystic follicles was a common finding. The average
      number of CL was 18.2 +/- 5.7 per sow (N = 16, range: 3-27) with no significant
      difference between the groups. Total embryo recovery was 79 +/- 13% with no
      significant difference between groups. The embryo diversity calculated as
      standard deviation of the maximum diameter was higher in the hCG group as
      compared with the control group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572452
TI  - Prostaglandin F2 alpha metabolite levels following an embryo transfer procedure
      in the mare.

PMID- 7572451
TI  - A field survey on anthelmintic resistance in equine small strongyles in Norway.
AB  - A field survey at 17 stables involving 221 horses was performed to evaluate the
      presence of anthelmintic resistance in the equine small strongyles
      (cyathostomes). The horses were allocated into treatment groups, and resistance
      to fenbendazole (FBZ), pyrantel pamoate (PYR) and ivermectin (IVM) was tested by
      the faecal egg count reduction test (FECR-test). Faecal samples were collected at
      the time of treatment, 14 days post treatment and 90 days post treatment.
      Resistance to FBZ, which was defined as a faecal egg count reduction < 95%, was
      found in 14 out of 17 stables. In 2 of the 14 stables the egg reductions were
      close to the limit of 95%, 91 and 93%, respectively. In 1 stable the egg
      reductions indicated resistance to PYR as well as detection of resistance to FBZ,
      94% reduction for PYR and 85% for FBZ. No signs of resistance were detected to
      IVM. The investigation was performed in late autumn and winter, and due to the
      climatic conditions and cleaning procedures in the stables no reinfection took
      place during this period. The faecal egg count reduction from treatment till day
      90 post treatment was used as an expression of the effect of PYR and IVM on the
      early stage (hypobiotic), late third stage and fourth stage larvae in the gut
      wall. This was justified because there was no reinfection and because the 14 day
      post treatment egg counts were zero or close to zero for the PYR and IVM
      treatment groups. The effects of PYR and IVM on the larval stages were compared
      and no statistically significant differences were found.

PMID- 7572453
TI  - Freeze-resistant Trichinella (Trichinella nativa) established on the Scandinavian
      peninsula.

PMID- 7572454
TI  - High velocity projectiles for killing whales. Hunting trials using 20 mm high
      velocity projectiles for minke whales in 1982.

PMID- 7572455
TI  - Serum concentrations of procollagen type III aminoterminal peptide in growing
      dogs with hip dysplasia.

PMID- 7572456
TI  - Salmonella isolated from animals and feedstuffs in Sweden during 1988-1992.
AB  - The present paper surveys the number of Salmonella isolations in animals and
      feedstuffs in Sweden during 1988-1992. It is the eighth in a series of reports
      published by the National Veterinary Institute (NVI) since 1949. During the
      period referred to, 602 outbreaks of Salmonella were reported in animals, both
      domestic and wild. Compared with the previous 5-year period there was a 20%
      reduction in the number of outbreaks (760). Fifty-six different serotypes were
      reported, 19 of which had never been isolated in any animal in Sweden previously.
      A temporary increase in the number of outbreaks in poultry was seen in 1991
      following an extended sampling before slaughter of layers. A remarkably high
      prevalence (38%) of Salmonella was observed in snakes in the wild. In 1990, the
      end-point testing of feeds was replaced by an approach based on HACCP (Hazard
      Analysis Critical Control Point) principles for the monitoring of feed mills.
      Significantly higher number of Salmonella positive samples were found by using
      this technique compared with the previous analysis of finished feed. It is
      concluded that the adopted Salmonella control program has contributed to a
      reduced number of Salmonella outbreaks in animals in Sweden.

PMID- 7572457
TI  - Osteochondrosis in wild boar-Swedish Yorkshire crossbred pigs (F2 generation).
AB  - Osteochondrotic lesions occur in very high frequency in growing pigs of all
      commercial breeds and are claimed to be associated with high growth rate, and not
      to occur, or to be milder, in slow-growing pigs. The present study monitored the
      magnitude and distribution of osteochondrotic lesions in a crossbred pig
      population of wild boar and Swedish Yorkshire ancestry. In this population,
      having a low growth rate, the distribution and extent of osteochondrotic lesions
      was similar to that of purebred Swedish Yorkshire pigs, and only weak
      relationships between the studied growth parameters and osteochondrosis could be
      found.

PMID- 7572458
TI  - Antibiotic resistance of Vibrio anguillarum, in relation to serovar and plasmid
      contents.
AB  - A total of 520 Vibrio anguillarum strains, isolated from fish and the
      environment, were tested for their sensitivity to 20 different antibiotics. Most
      isolates were of European origin. The results were compared with data on the O
      serogroup and plasmid contents. All strains were sensitive to neomycin,
      spectinomycin, nitrofurantoin, flumequine and oxolinic acid, while most strains
      were sensitive to streptomycin, oxytetracycline, chloramphenicol, sulphonamides,
      trimethoprim, sulphonamides with trimethoprim, nalidixan, rifampicin, novobiocin
      and O/129. A major part of the strains were resistant to the macrolides,
      spiramycin and lincomycin. For ampicillin, cephalothin, and colistin marked
      differences were recorded with respect to O-serogroup. Most O1 strains were
      resistant to colistin and sensitive to ampicillin and cephalothin, while most O2
      strains were sensitive to colistin but resistant to ampicillin and cephalothin.
      Some antibiotic resistant strains carried plasmids but no conjugation experiments
      were carried out to detect possible R factors.

PMID- 7572459
TI  - Induced acute ruminal acidosis in goats treated with yeast (Saccharomyces
      cerevisiae) and bicarbonate.
AB  - Ruminal acidosis was induced in twenty-one 10-month-old West African Dwarf Goats
      by feeding a suspension of 80 g wheat flour per kg bodyweight (day 0) through a
      stomach tube. Ruminal and systemic acidosis was diagnosed on day 1 in all goats.
      Clinical signs included loss of rumination and appetite, trembling, and watery
      diarrhoea. The detection of acidic faeces during the first 24h was considered of
      diagnostic importance. Subgroups were treated orally on days 1, 2, and 3 either
      with 1 g of sodium bicarbonate per kg bodyweight, with 1 g of baking yeast per
      kg, or with a combination of these treatments at 0.5 g of each per kg. A fourth
      group served as untreated controls. Peroral bicarbonate neutralization was highly
      effective in the treatment of rumen acidosis, whereas the use of yeast was found
      ineffective. The combined treatment had a moderate effect probably due to the
      bicarbonate. Three fatal cases (60%) occurred in the untreated group compared
      with none in the bicarbonate group, and 2 in each of the remaining groups. This
      corresponded to 33% of the yeast treated group and 40% of the combined treated
      group. Details were given on post mortem examinations performed on all survivors
      on day 11. Lesions included subacute rumenitis and abomasal ulcers. No lesions
      were found in 3 of the bicarbonate treated goats and in 2 of the animals
      receiving combined treatment.

PMID- 7572460
TI  - Survival of salmonellas and Ascaris suum eggs in a thermophilic biogas plant.
AB  - In a continuous biogas plant, receiving manure from 200 dairy cows and 400 calves
      and young stock, survival of salmonellas and Ascaris suum eggs was studied. The
      bacteria and parasite eggs were kept in filter sacs in the manure that had a
      temperature of 55 degrees C. No viable salmonellas or Ascaris suum eggs could be
      found after 24h in the digester. Survival of salmonellas and Ascaris suum eggs
      was also studied in the manure pit where the manure was stored after digestion.
      The temperature in the manure pit varied between 22-27 degrees C. Salmonellas
      survived 35 but not 42 days. On day 56, when the experiments had to be stopped,
      60% of the Ascaris eggs were viable.

PMID- 7572461
TI  - Rabies antibodies in vaccinated dogs.
AB  - Forty-seven healthy, owned dogs were vaccinated with Madivak and 85 with Rabisin.
      Geometric mean titres of 17.40 and 1.03 IU/ml were measured by the rapid
      immunofluorescent focus inhibition test 30-40 and 350-370 days, respectively,
      after a single injection. Four out of 130 (3.1%) and 18 out of 106 (17%) dogs had
      a titre of less than 0.5 IU/ml in serum 30-40 and 350-370 days after vaccination.
      Twenty-one dogs (19.8%) had a titre of 0.5 IU/ml 350-370 days after vaccination.
      There was no significant difference in antibody levels between animals vaccinated
      with Rabisin or Madivak. Our results indicate that a booster is always necessary
      after a single injection to ensure that all dogs have a lasting antibody titre.

PMID- 7572462
TI  - Survival of oocysts of Eimeria alabamensis on pastures under different climatic
      conditions in Sweden.
AB  - The extent to which oocysts of the coccidian parasite Eimeria alabamensis can
      survive the winter and cause clinical coccidiosis in different parts of Sweden
      was investigated. Fecal samples were collected between May and July 1993 from
      calves on 59 farms where calves had grazed the same pasture for at least 5
      consecutive years. The farms were situated in 9 regions of Sweden with different
      climatic conditions in the winter. On each farm, 5 samples of feces were
      collected from the floor of the calf-house before the calves were turned out in
      the spring, and again from the pasture on days 4 or 5, 8 or 9 and 10 or 11 after
      they were turned out. Overwintering of oocysts of E. alabamensis was considered
      to have occurred if an increase in the excretion rate of oocysts of this species
      could be demonstrated 8 to 11 days after calves had been turned out to pastures
      that had not been grazed since the previous autumn. Oocysts were shown to have
      overwintered on 27 farms, representing all 9 regions. Samples from 20 (34%) of
      the farms representing all the climatic regions contained more than 850,000
      oocysts per g of feces. This was comparable with the numbers found in animals
      with clinical coccidiosis due to E. alabamensis. Delaying turnout until the
      beginning of July did not affect the infection rate of the calves. However,
      calves which were turned out to pastures that had been grazed by older cattle or
      horses, either earlier in the spring or in previous years, excreted significantly
      fewer oocysts than calves which were turned out to pastures that had been grazed
      only by calves. A questionnaire answered by 321 dairy farmers revealed that of
      the 298 farmers who turned their first-season grazing cattle out to traditional
      pastures, 179 (60%) had used the same pasture for at least 5 years. These 179
      farmers had experienced a significantly higher incidence of diarrhoea in their
      calves during the first 2 weeks at pasture than those farmers who had used
      different pastures.

PMID- 7572463
TI  - Fatty acid composition of porcine muscle and adipose tissue lipids as affected by
      anatomical location and cod liver oil supplementation of the diet.
AB  - In pigs fed a standard pig mash the contents of polyunsaturated fatty acids
      (PUFAs) of both the n-6 and n-3 series were significantly higher in the dark red
      mm adductores compared to the light coloured m longissimus lumborum. Perirenal
      fat had a higher concentration of saturated fatty acids (14:0, 16:0, 18:0) than
      backfat, and a lower concentration of monounsaturated fatty acids, such as 16:1n
      7 and 18:1n-9. Daily supplementation of 50 ml cod liver oil, rich in n-3 PUFAs,
      during the fourth and third week before slaughter led to a 1.4 to 1.7 times
      increase in the contents of n-3 PUFAs in muscles and fat depots. There was no
      difference between the incorporation of n-3 PUFAs in dark and light muscles.
      Perirenal fat contained more 20:5n-3 (EPA) and 22:6n-3 (DHA), but less 20:1n-9
      (eicosenoic acid) than the backfat, after cod liver oil supplementation rich in
      these 3 fatty acids. Supplementation of cod liver oil reduced the n-6/n-3 fatty
      acid ratio in all anatomical locations examined.

PMID- 7572464
TI  - Detection of herpes simplex virus DNA by polymerase chain reaction in the
      cerebrospinal fluid of patients with viral meningoencephalitis using primers for
      the glycoprotein D gene.
AB  - A novel set of primers for polymerase chain reaction (PCR) which amplified the
      portion of US6 sequence coding for the main type-common neutralizing epitope of
      glycoprotein D (gD) was used for detection of herpes simplex virus (HSV) DNA in
      44 cerebrospinal fluid (CSF) samples from 29 patients with clinical symptoms of
      viral meningitis or meningoencephalitis. The primers in question amplified the
      DNA of 9 out of 10 low-passage HSV-1 isolates and of 5 out of 10 HSV-2 low
      passage isolates as well as the DNA of all laboratory strains examined when
      tested in the supernatant fluid of infected cells cultures. The PCR was positive
      in 5 CSF samples (taken on days 2, 4, 8, 10 and 56 after the onset of symptoms,
      but not later than day 8 after starting acyclovir (ACV) therapy) obtained from 4
      patients with intrathecal antibody response. The PCR was repeatedly negative in
      CSF of 15 patients who had antibodies to HSV in serum and CSF, but did not show
      intrathecal antibody production. It was also negative in 10 patients who had no
      HSV antibodies in CSF. Our results confirmed that positive PCR for HSV DNA in the
      CSF is an indication for starting and/or continuing ACV therapy even in the
      absence of classical symptoms of HSV encephalitis.

PMID- 7572465
TI  - A model to study cytokine profiles in primary and heterologously secondary Dengue
      2 virus infections.
AB  - Roles of cytokines in primary and secondary Dengue virus (DV) infections are not
      completely understood. In this study, we challenged mononuclear leukocytes (MNLs)
      obtained from non-immune and DV-1-infected donors with DV-2 in vitro to mimic
      primary and heterologously secondary DV-2 infections, respectively. We found that
      MNLs in response to DV-2 could release a large amount of interleukin-1 (IL-1
      beta) and tumor necrosis factor alpha (TNF alpha). However, IL-1 beta and TNF
      alpha released by MNLs with primary or heterologously secondary exposure to DV-2
      were not significantly different. In contrast, MNLs with heterologously secondary
      DV-2 infections produced significantly higher amount of interferon gamma (IFN
      gamma) than those with primary DV-2 infections. These results suggest that IFN
      gamma, but not TNF alpha or IL-1 beta, may in part participate in the
      pathogenesis of Dengue shock syndrome (DSS) frequently found in heterologously
      secondary DV-2 infections.

PMID- 7572466
TI  - Genomic characterization of type 1 Sabin-related polioviruses isolated in Brazil.
AB  - Eight strains of P1/Sabin-derived polioviruses isolated in Brazil from paralysis
      cases were analyzed. The serotypes of the viral isolates were identified by
      neutralization test with hyperimmune equine sera. The relationship of the
      isolates to the P1/Sabin strain was demonstrated by molecular hybridization and
      PCR. The isolates were partially sequenced with the objective of finding
      mutations at nucleotides (nt) 480 and 525 of the 5'-noncoding region (5' NCR) and
      at nt 6203 of the 3Dpol coding region (3Dpol), which are important for reversion
      towards neurovirulence. Four isolates from paralysis cases classified as Guillain
      Barre Syndrome (GBS; three with sequels) were analyzed; one presented G-->A (480)
      and C-->U (6203) mutations, one G-->A (480) mutation, one G-->A (480) and U-->C
      (525) mutations, and one did not mutate at the analyzed positions. Two isolates
      from transient facial paralysis cases were analyzed; one presented U-->C (525)
      mutation and the other G-->A (480) mutation. One isolate from a transient
      paralysis case classified as a neuroviral disease and one isolate from a
      paralysis case with sequels were analyzed and none mutated at the analyzed
      positions. Although the isolates may not be the causative agent of the disease, a
      temporal association between the isolation of the P1/Sabin-derived isolates and
      the disease was observed. The possibility that GBS and the facial paralysis were
      caused by these isolates could not be excluded.

PMID- 7572467
TI  - Post-inoculation changes in enzyme activity of Aedes aegypti infected with
      Chikungunya virus.
AB  - Levels of acetylcholinesterase, non-specific esterases, glutathione-S-transferase
      and glucose-6-phosphate dehydrogenase in Aedes aegypti (L.) mosquitoes inoculated
      intrathoracally with Chikungunya virus were elevated, as compared to uninoculated
      control insects. A number of these enzymes are important in the insects defence
      mechanism against xenobiotics, such as pesticides. Malathion bioassays indicated
      a reduction in the susceptibility of experimentally injected insects with virus
      or virus-free inoculum, compared to non-inoculated controls. However, insects
      which were mock-inoculated (injected with no inoculum) showed a similar reduction
      in susceptibility suggesting that the observed effect was due to the mobilization
      of a defence reaction in the mosquitoes in response to injury during inoculation.

PMID- 7572468
TI  - Herpes simplex virus type 1 envelope subunit vaccine not only protects against
      lethal virus challenge, but also may restrict latency and virus reactivation.
AB  - A subunit vaccine containing the main antigenic components of herpes simplex
      virus 1 (HSV-1) was tested in Balb/c mice and albino rabbits. The mice were
      completely protected against challenge with 10 LD50 of the highly pathogenic SC16
      strain given by intraperitoneal (ip) route when immunized with 1000 antigen units
      (ELISA) corresponding to 110 micrograms of protein. The animals were protected
      against lethal disease when immunized with 1-33 micrograms of protein per dose.
      Immunization of rabbits with 3000 antigen units prior to inoculation of strain
      Kupka into right scarified cornea limited the establishment of latency in the
      trigeminal ganglia. Both the number of animals in which latency had been
      established as well as the number of homolateral sensory ganglion cells which had
      become virus carriers were reduced. However, the effect of immunization was less
      striking at preventing HSV reactivation in rabbits vaccinated after infection.
      When shedding of reactivated HSV was elicited by repeated epinephrine
      iontophoresis to cornea, there was no quantitative difference between the
      immunized and mock-immunized groups, only the period between stimulation and the
      onset of virus shedding was prolonged in immunized rabbits (from 3.6 to 5.6 days,
      p < 0.05). But if the corneas were stimulated by a single iontophoresis
      procedure, the duration of virus shedding was significantly reduced from 5.6 days
      in the mock-immunized rabbits to 1.7 days in the immunized ones (p < 0.025). In
      the latter experiment, the total number of positive swabs during 14 days of the
      post-stimulation period was higher in the mock-immunized animals (31 of 171,
      18.1%) than in the immunized ones (12 of 162, 7.4%; p < 0.025).

PMID- 7572470
TI  - Optimum conditions for the storage of potato virus S.
AB  - The effect of storage conditions on the serological activity of two strains of
      potato virus S (PVS), Andean and the ordinary, was studied by ELISA. Virus
      purificates, infected leaves and their homogenates, stored in lyophilized, frozen
      and dissolved form at various temperatures were tested. Virus purificates were
      most stable in lyophilized form, their activity decreased after 9 months only by
      20-30%. Also non-purified virus was most stable as a lyophilized leaf homogenate,
      its activity decreased after 12 months by 30%. When lyophilized leaves were
      stored, the virus activity dropped after 12 months by 45%. Both the Andean and
      the ordinary strain of PVS behaved similarly during storage under the conditions
      tested.

PMID- 7572469
TI  - Inhibition of influenza virus protein synthesis by a plant preparation from
      Geranium sanguineum L.
AB  - A polyphenolic complex (PC) with antiviral properties has been isolated from the
      Bulgarian medicinal plant Geranium sanguineum L. A study was undertaken to
      investigate the effect of PC on virus-specific protein synthesis in influenza
      virus-infected cells. The expression of viral glycoproteins on the surface of
      chick embryo fibroblasts infected with virus A/FPV, strain Rostock (H7N1) was
      suppressed. Virus protein synthesis was selectively inhibited as shown by SDS
      polyacrylamide gel electrophoresis of 35S-methionine-labelled proteins and
      proteins immunoprecipitated with monoclonal antibodies. The inhibitory effect was
      dose-dependent and better pronounced when PC was applied after virus infection.
      Two variants of influenza virus FPV/Rostock with reduced drug susceptibility were
      selected. PC affected to a lesser extent the synthesis of viral proteins in cells
      infected with the variants as compared to the sensitive parental virus.

PMID- 7572471
TI  - Marek's disease and new approaches to its control.
AB  - Marek's disease (MD) is a lymphoproliferative disorder induced by a herpesvirus.
      Several factors, including those virus-encoded and host-dependent, affect the
      course of the disease. Existing vaccination program is based on the use of
      attenuated strains of MD virus (MDV) serotype 1 and on strains of non-oncogenic
      serotype 2 (MDV2) and serotype 3 (herpesvirus of turkey-HVT) viruses. Failures
      resulting in disease progress have been reported and indicate need for production
      of new, more effective vaccines. It is likely that future development of MD
      vaccines will rely on recombinant molecules technology.

PMID- 7572472
TI  - W. C. Roentgen and the discovery of the Roentgen rays.

PMID- 7572473
TI  - The new light: discovery and introduction of the X-ray.

PMID- 7572474
TI  - The X-ray enters the hospital.

PMID- 7572475
TI  - American martyrs to radiology. Eugene Wilson Caldwell (1870-1918). 1936.

PMID- 7572477
TI  - William H. Crane of Cincinnati and the first irradiation of the pediatric thymus,
      1905.

PMID- 7572476
TI  - Professor William F. Magie and the American discovery of the fluoroscope, 1896.

PMID- 7572478
TI  - Nonoperative treatment of intussusception: historical perspective.

PMID- 7572479
TI  - History of the department of radiology at the University of Iowa.

PMID- 7572480
TI  - 1896: the first year of X-rays in Colorado.

PMID- 7572481
TI  - CT angiography.
AB  - CT angiography is an exciting yet controversial application of helical (spiral)
      CT technology. Although many radiologists equate CT angiography with three
      dimensional (3D) rendering, we believe that axial images, multiplanar reformatted
      (MPR) images, and true 3D models all contribute to a better evaluation of the
      vascular system than was possible with conventional CT. This occurs because
      helical scans are volumetric and are accomplished rapidly with high levels of
      circulating contrast material. This article reviews the indications for CT
      angiography, compares CT angiography with other techniques, and offers a
      practical methodology for neuroradiologic, thoracic, and abdominal applications
      of CT angiography.

PMID- 7572482
TI  - Complications of laparoscopic cholecystectomy: imaging and intervention.
AB  - Cholecystectomy is the most common abdominal operation done in the United States,
      with more than half a million cholecystectomies performed annually. Recently,
      there has been a trend to perform laparoscopic, rather than open,
      cholecystectomy. The introduction of any new technique involves a learning curve
      for surgeons, and several complications may occur with this procedure.
      Radiologists may be called on to help diagnose and manage injuries occurring
      after laparoscopic cholecystectomy. This article will review the complications of
      laparoscopic cholecystectomy, emphasizing the role of imaging in both diagnosis
      and nonsurgical management of these injuries.

PMID- 7572484
TI  - Fast MR imaging: technical strategies.
AB  - Since the introduction of MR imaging for medical use in the early 1980s, there
      has been a continuous trend toward reduction in scan times. Whereas it took over
      24 hr to acquire and display the earliest MR images [1], scan times of well under
      a second are now feasible. The trend toward shorter scan times is based on a need
      to reduce motion-related artifacts, to provide more comprehensive studies in a
      reasonable examination time (such as those with multiple pulse sequences,
      multiple planes, or contrast media), or to increase patient throughput to reduce
      per-patient examination costs.

PMID- 7572483
TI  - Dissection of the internal carotid and vertebral arteries: imaging features.
AB  - Dissection of either the internal carotid artery or the vertebral artery
      (cervicocephalic arterial dissection) was once considered uncommon. However, in
      the past few decades, it has been increasingly recognized as a cause of stroke in
      young and middle-aged adults. Dissection causes only 0.4-2.5% of all strokes in
      the general population but causes 5-20% of strokes among young patients.
      Anticoagulant therapy is usually started immediately after the dissection is
      diagnosed. The clinical and radiologic features are important to recognize so
      that anticoagulation therapy can be started promptly, thereby minimizing the
      risks of infarction, permanent neurologic disability, and death.

PMID- 7572485
TI  - Video-assisted thoracic surgery: the current state of the art.
AB  - Surgical thoracoscopy (or pleuroscopy) has historically been underused in the
      diagnosis and therapy of diseases of the chest. The rapid developments in
      laparoscopy in recent years caused thoracic surgeons to reconsider the use of
      endoscopic techniques in surgery of the chest. Advances in video camera
      technology and the use of digital processing technology so expanded the potential
      of thoracoscopy that an entirely new set of procedures, called video-assisted
      thoracic surgery, has emerged. This article reviews situations in which video
      assisted procedures have proven useful, the techniques by which these procedures
      are performed, and the rationale behind using the video-assisted in lieu of the
      open approach. Video-assisted surgery often allows one to accomplish the same
      goal as the comparable open procedure but with less morbidity and a shorter
      hospital stay. With continued development of instrumentation, increasingly
      complex procedures continue to be accomplished. It is important for radiologists
      to be aware of these new developments in minimally invasive surgery, as the
      techniques have major implications for the practice of chest medicine and surgery
      as a whole. The evolution of the management of the solitary pulmonary nodule is
      but one example of the way video-assisted thoracic surgery has called into
      question the traditional approach to diseases of the chest.

PMID- 7572486
TI  - Posttransplant lymphoproliferative disorder of the lung.

PMID- 7572487
TI  - Pulmonary arteriovenous malformations: results of treatment with coil
      embolization in 53 patients.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of percutaneous
      transcatheter coil embolization of pulmonary arteriovenous malformations on
      arterial oxygen saturation, pulmonary gas exchange, anatomic right-to-left shunt,
      and lung function and to assess the complications of the procedure. SUBJECTS AND
      METHODS: Fifty-three patients were included in the study: 42 (79%) had associated
      hereditary hemorrhagic telangiectasia. Nineteen (36%) had neurologic problems
      compatible with paradoxical embolization. During 102 separate embolization
      procedures, all malformations with feeding vessels > or = 3 mm in diameter were
      embolized with steel coils. Arterial oxygen saturation at rest and on exercise
      and the intrapulmonary right-to-left shunt fraction (99mTc-macroaggregate
      injection), forced expiratory volume in 1 sec, vital capacity, diffusing capacity
      for carbon monoxide, and transfer coefficient were measured before and after
      embolization. Complications of the procedure were recorded and investigated.
      RESULTS: Before treatment, all patients had hypoxemia in the supine posture
      (SaO2, 89 +/- 1% [standard error of the mean]), which fell a further 6%
      (absolute) on standing. Mean values for transfer coefficient and diffusing
      capacity for carbon monoxide were reduced, at 85 +/- 3% and 78 +/- 3% (predicted
      value), respectively. After embolization, the mean values for supine and erect
      SaO2 rose to 94 +/- 1% and 93 +/- 1%. Transfer coefficient increased by a mean of
      5.4% of predicted value. The mean shunt fraction fell from 23 +/- 2%
      preembolization to 9 +/- 1% postembolization. In 102 procedures, there were 18
      complications, 12 mild, two moderate, and four potentially serious (systemic coil
      embolization in two patients, cerebrovascular accident [transient], and
      myocardial puncture), but there were no lasting sequelae. CONCLUSION: Our results
      show that coil embolization is an effective and well-tolerated method for
      treatment of pulmonary arteriovenous malformations. Improvements in pulmonary gas
      exchange and lung function and a decrease in right-to-left shunting occurred
      after treatment. The procedure was well tolerated and had a low complication
      rate.

PMID- 7572488
TI  - Type 2 pulmonary laceration: a marker of blunt high-energy injury to the lung.

PMID- 7572489
TI  - Quantification of pneumothorax size on chest radiographs using interpleural
      distances: regression analysis based on volume measurements from helical CT.
AB  - OBJECTIVE: The aim of this study was to define the relationship between
      interpleural distance measurements on an erect posteroanterior chest radiograph
      and pneumothorax size as measured by helical CT in a series of patients. SUBJECTS
      AND METHODS: Twenty pneumothoraces from 19 patients (10 males, nine females) were
      analyzed. Most pneumothoraces were on the right side (n = 16). The etiology was
      spontaneous in seven patients and iatrogenic in thirteen. All patients underwent
      an erect inspiratory posteroanterior radiograph and a helical CT scan of the
      thorax on the same visit to the radiology department. The interpleural distance
      was measured at three locations and the figures added together. Following helical
      CT of the thorax, the percentage pneumothorax size was calculated by drawing
      regions of interest around the relevant hemithorax and lung on 10-mm
      reconstructed slices. A scattergram of the sum of interpleural distances in
      centimeters versus percentage pneumothorax size was plotted. RESULTS: Analysis of
      results showed that percentage pneumothorax size could be calculated by the
      formula Y = 4.2 + [4.7 x (A + B + C)], r = .98, p < .0001. CONCLUSION: This study
      identified a formula for accurately calculating percentage pneumothorax size as
      determined by helical CT from an erect posteroanterior radiograph. Using this
      formula with the clinical status of the patient should more easily identify
      patients requiring active intervention.

PMID- 7572491
TI  - Informed consent for percutaneous lung biopsy: comparison of two consent
      protocols based on patient recall after the procedure.
AB  - OBJECTIVE: Informed consent is now required for the majority of radiologic
      procedures, but few studies have evaluated the efficacy of informed consent
      protocols. We compared our standard consent protocol of obtaining consent prior
      to percutaneous lung biopsy with a modified protocol by using patients' recall of
      procedure risks after the biopsy as an indicator of patients' comprehension.
      SUBJECTS AND METHODS: The study sample consisted of 50 patients who underwent
      percutaneous lung biopsy between December 1992 and June 1994. Twenty-seven
      patients received our standard informed consent procedure in which four important
      procedure risks were described briefly using our standard method. Twenty-three
      patients underwent a consent procedure that had the following modification. After
      the four procedure risks were described, the patient was tested verbally until
      all risks could be recited to the physician. This change required 5 additional
      min at most. In both protocols, efficacy of the procedure was evaluated by
      testing patient recall 4 hr after consent was obtained. We also assessed any
      effect that might have been introduced by differences between the groups, age,
      sex, time between consent and recall, and complications during the procedure.
      RESULTS: Patients' recall was significantly better in the modified consent group
      than in the standard group (p = .005). This result could not be attributed to
      differences in age, sex, or time between consent and recall. There was a trend
      for improved recall in patients with complications. This trend did not appear to
      influence our principal finding. CONCLUSION: The standard consent procedure for
      lung biopsy appears inadequate when patients' recall of procedure risks later is
      used as a measure of the patients' comprehension. Based on this study, the
      informed consent process may be improved substantially by teaching patients to
      recite the procedure risks to the physician as part of the informed consent
      protocol.

PMID- 7572490
TI  - Diagnosis of central pulmonary embolism with helical CT: role of two-dimensional
      multiplanar reformations.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of multiplanar two
      dimensional (2D) reformations in the diagnosis of central pulmonary embolism with
      helical CT. SUBJECTS AND METHODS: Thirty-five patients with suspected pulmonary
      embolism underwent contrast-enhanced helical CT of the pulmonary arterial tree.
      Two sets of images were analyzed: overlapped transverse sections and 2D
      reformatted images of 10 obliquely oriented arteries (intralobar pulmonary
      artery, A2, A4+5, A6, and A10 [A = artery]) selected on three-dimensional shaded
      surface displays of each pulmonary arterial tree. RESULTS: Among the 20 patients
      with unequivocal central pulmonary emboli on transverse sections (group 1), 2D
      reformations enabled a more precise analysis of the extent of thromboembolic
      disease in 13 cases. These patients underwent no further diagnostic procedure. In
      six patients (group 2), transverse sections alone excluded central pulmonary
      embolism with angiographic (n = 2) or scintigraphic (n = 4) confirmation. No
      additional information was provided with the 2D reformations. In nine patients
      with an uncertain diagnosis of pulmonary embolism on transverse sections (group
      3), 2D reformations enabled us to exclude central emboli in all the cases, with
      angiographic (n = 4) or scintigraphic (n = 5) confirmation. In groups 1 and 3, 2D
      reformations provided adequate visualization of obliquely oriented arteries (n =
      30) and enabled assessment (n = 2) or exclusion (n = 28) of endovascular changes,
      a clear distinction between endoluminal and perivascular abnormalities (n = 7),
      or a precise evaluation of extensive mural thrombi (n = 6). CONCLUSION: Our
      results show that 2D reformations enable confident exclusion of pulmonary
      embolism on inconclusive helical CT examinations and improve analysis of the
      extent of thromboembolic disease.

PMID- 7572492
TI  - Benign fibrous mesothelioma of the pleura: MR imaging findings.

PMID- 7572493
TI  - Hepatic artery stenosis in liver transplant recipients: prevalence and
      cholangiographic appearance of associated biliary complications.
AB  - OBJECTIVE: The occurrence of biliary strictures or bile duct necrosis in liver
      transplant recipients with hepatic artery stenosis has been well documented. This
      study was done to determine the prevalence and cholangiographic appearance of
      biliary complications in liver transplant recipients with hepatic artery stenosis
      and to determine if such complications occur with increased frequency compared
      with transplant recipients with patent hepatic arteries. MATERIALS AND METHODS:
      The study population consisted of 33 patients (17 male, 16 female; 1-65 years
      old) with angiographically proven significant hepatic artery stenosis after liver
      transplantation. All patients had T-tube or percutaneous transhepatic
      cholangiography performed within 4 months of hepatic arteriography. A
      retrospective review of radiographs was done to determine the prevalence and
      appearance of biliary complications in the study group compared with a control
      group of 58 patients with angiographically patent hepatic arteries who had liver
      transplants during the same period. RESULTS: Biliary complications were
      significantly more prevalent in patients with hepatic artery stenosis, with 22
      (67%) showing cholangiographic abnormal findings compared with 16 (28%) in the
      control group (p = .001). The most significant abnormalities in patients with
      arterial stenosis were nonanastomotic biliary strictures seen in 16 (49%),
      compared with 13 (22%) in the control group (p = .04). Other findings
      (intraductal filling defects, anastomotic biliary stricture, and anastomotic bile
      leak) showed no statistically significant difference between the study and
      control groups. CONCLUSION: Biliary complications are significantly more
      prevalent in liver transplant recipients with hepatic artery stenosis. The most
      common complication seen on cholangiography was nonanastomotic biliary stricture.

PMID- 7572494
TI  - Cavernous transformation of the portal vein: patterns of intrahepatic and
      splanchnic collateral circulation detected with Doppler sonography.
AB  - OBJECTIVE: Cavernous transformation of the portal vein is defined as the
      formation of venous channels within or around a previously thrombosed portal
      vein. The purpose of this work was to study the hemodynamic consequences of
      cavernous transformation of the portal vein in a group of afflicted patients by
      use of Doppler sonography. We wished to study the evolution from portal vein
      thrombosis to the formation of cavernous transformation, the extent of resulting
      extrahepatic collateral channels, and the patterns of splanchnic collateral
      circulation. MATERIALS AND METHODS: Seventy-five patients (48 adults and 27
      children) with cavernous transformation of the portal vein were studied with
      color and/or pulsed Doppler sonography. Blood flow in the extrahepatic portal
      vein, in its segmental branches, in the hepatic veins and artery, and in the
      splanchnic veins was examined. Collateral pathways were sought. For nine patients
      with acute thrombosis of the portal vein, serial examinations were performed
      during the formation of cavernous transformation. RESULTS: In nine patients, a
      fresh thrombus filled and distended the portal vein and became recanalized within
      a few days. Tortuous vessels appeared at the porta hepatis. These were
      characterized as veins or arteries with Doppler sonography. Soon the portal vein
      could no longer be identified within the mass of tortuous vessels. The cavernous
      transformation developed within 6-20 days of the acute thrombosis. A spongelike
      mass of collateral vessels around the main portal vein was seen in all but two
      patients. Intrahepatic extension of the cavernous transformation was seen in 57
      patients (76%) and involved one or more intrahepatic portal veins. Two types of
      collateral circulation were observed: portosystemic, mainly through the left
      gastric and the perisplenic veins (the caput medusae, i.e., the paraumbilical-to
      abdominal venous route, was never seen); and portoportal, from the periportal or
      pericholecystic venous channels to the intrahepatic portal veins. In nine
      patients, flow within unaffected intrahepatic branches of the portal vein was
      reversed as directed toward the cavernous transformation surrounding other,
      thrombosed intrahepatic segments of the portal vein. CONCLUSION: After thrombosis
      of the portal vein, portoportal venous channels may form not only at the porta
      hepatis but also within the liver. Intrahepatic blood may be shunted from one
      segmental portal vein to another. In addition, portosystemic collateral channels
      are formed, suggesting that, despite extensive hemodynamic adaptations, portal
      hypertension ensues.

PMID- 7572496
TI  - Hydatid cysts of the liver: long-term results of percutaneous treatment using a
      cutting instrument.
AB  - OBJECTIVE: We previously reported a technique for percutaneous drainage of
      hydatid cysts of the liver using a cutting instrument. The purpose of this study
      was to review the efficacy of this procedure in a large series of patients.
      SUBJECTS AND METHODS: The study included 32 patients each with a single hydatid
      cyst of the liver. Sixteen cysts were univesicular, nine were multivesicular, and
      four had a ruptured membrane. Two were infected, and one was calcified. Using a
      coaxial system, a large-bore cutting aspiration device was percutaneously
      introduced. Initial success consisted of complete evacuation of cyst contents
      plus absence of laminated membranes and daughter cysts on a cystogram performed 2
      weeks later. Catheter drainage was continued until it was < 20 ml/day (mean, 4
      weeks; median, 3 weeks). Patients underwent clinical and imaging follow-up
      examinations for between 9 and 48 months (mean, 25.5 months; median, 20 months).
      Follow-up imaging included monthly sonographic examinations for 6 months, control
      CT at 6 months, and sonographic and CT studies at 1-year intervals. All
      complications were recorded. RESULTS: A single aspiration and drainage procedure
      removed the liquid and solid cyst contents in 90% of the patients. Minor
      complications were limited to transient vasovagal reaction, mild fever that
      cleared without antibiotics, and reactive pleural effusion (19%). Three patients
      (10%) required a second intervention either to evacuate residual laminated
      membrane or to drain an abscess that developed within an incompletely evacuated
      cyst (one case). Eleven patients had bile in the drainage fluid. A biliary
      fistula was seen in five of those. No sign of recurrence was observed. Complete
      obliteration of the cavity was observed within six months in all cases. Complete
      reconstitution of hepatic parenchyma was shown by either sonographic or CT
      examinations within 1 year in 21 cases (66%). CONCLUSION: Results in a large
      group of patients indicate that the treatment of hydatid liver cysts with a
      cutting aspiration device is safe, effective, and reliable. It provides a high
      incidence (90%) of initial success with a low incidence of major complications
      (3%). Long-term follow-up has demonstrated no recurrence in the follow-up period.

PMID- 7572495
TI  - Gadoteridol-enhanced MR imaging of malignant hepatic tumors: effects of triple
      versus standard doses on lesion-liver contrast.
AB  - OBJECTIVE: The purpose of this study was to compare liver signal-to-noise ratio
      (SNR), lesion SNR, and lesion-liver contrast-to-noise-ratio (CNR) in patients
      with malignant liver lesions after the administration of a standard dose (0.1
      mmol/kg of body weight) or a triple dose (0.3 mmol/kg) of a gadolinium chelate
      (gadoteridol). We hypothesized that the higher dose would produce a higher lesion
      liver CNR and therefore increase the conspicuity of hepatic lesions. MATERIALS
      AND METHODS: A total of 85 patients with malignant hepatic masses (61 metastases,
      22 hepatocellular carcinomas, and two lymphomas) proved by histologic or follow
      up studies underwent MR imaging at 1.5 T. T1-weighted spin-echo imaging and
      gradient-echo imaging were done before and within 1 min after (gradient echo) as
      well as 5 (spin echo) and 15 (spin echo) min after the injection of 0.1 or 0.3
      mmol of gadoteridol per kg, randomized before the start of the study (39 patients
      received the standard dose, and 46 received the triple dose). The signal
      intensities of the liver and lesions and the SD of background noise were measured
      by use of regions of interest to calculate the SNR of the liver and malignant
      lesions and the lesion-liver CNR. RESULTS: The lesion-liver CNR was increased
      significantly at 5 and 15 min after the administration of gadoteridol. No
      significant differences in the liver SNR, lesion SNR, and lesion-liver CNR (after
      1 min: standard dose, -5 +/- 8, and triple dose, -4 +/- 14; after 5 min: standard
      dose, -1 +/- 5, and triple dose, 2 +/- 8; and after 15 min: standard dose, 1 +/-
      5, and triple dose, 6 +/- 20) were found between the doses at all time points.
      CONCLUSION: Triple-dose gadoteridol does not improve the lesion-liver contrast of
      malignant hepatic lesions over that provided by the standard dose and is not
      warranted for liver MR imaging.

PMID- 7572497
TI  - Sonographic diagnosis of unsuspected gallbladder cancer: imaging findings in
      comparison with benign gallbladder conditions.
AB  - OBJECTIVE: Several sonographic findings were analyzed to determine their
      significance in distinguishing gallbladder cancer from benign conditions of the
      gallbladder. The analyzed findings were gallstone number and size; floating
      stones; displaced stones; wall thickening, irregularity, and echogenicity;
      mucosal plaque; intraluminal mass; gallbladder-replacing mass; invasive
      gallbladder mass; gallbladder mucosal discontinuity; hyperechoic gallbladder
      mucosa; and submucosal or transmural echolucency. MATERIALS AND METHODS:
      Sonograms of 20 patients with unsuspected, pathologically proven gallbaldder
      cancer and 65 patients with benign gallbladder conditions (predominantly acute or
      chronic cholecystitis) were retrospectively assessed by two observers who were
      unaware of experimental conditions. Gallstone number and size were assessed, and
      the presence of floating stone (neither settling nor wall-adherent), displaced
      stone (lifted from the gallbladder wall by mass or focal wall thickening), wall
      irregularity, mucosal plaque, intracystic mass, and gallbladder-replacing or
      invasive mass was evaluated. The echogenicity pattern of the gallbladder wall was
      characterized, and its thickness was measured and classified as normal/mildly
      thickened (< 7 mm) or moderately/severely thickened (> or = 7 mm). In addition,
      the gallbladder wall was evaluated for discontinuous mucosal echo, hyperechoic
      mucosa, submucosal or mural echolucency, and pericholecystic fluid collection.
      Sonographic findings were compared by the Mann-Whitney test for nonparametric
      variables and by Student's t test for continuous variables. RESULTS: Solitary
      gallstone, displaced stone, intraluminal mass, gallbladder-replacing or invasive
      mass, and discontinuity of the mucosal echo were all statistically significantly
      more common in patients with gallbladder cancer (.001 < p < .05). Mucosal plaque
      and wall irregularity were nonspecific findings. Gallbladder wall thickening by
      itself was nonspecific, although associated echolayering, transmural or
      submucosal edema, or a distinctly specular mucosal lining favored benign
      etiologies. CONCLUSION: Several sonographic findings were significantly more
      common in patients with gallbladder cancer compared with patients with benign
      gallbladder conditions. Assessment of these signs may be helpful in
      distinguishing gallbladder cancer from benign conditions of the gallbladder.

PMID- 7572498
TI  - Islet cell tumors of the pancreas: pathologic-imaging correlation among size,
      necrosis and cysts, calcification, malignant behavior, and functional status.
AB  - OBJECTIVE: The purpose of our study was to correlate the imaging and pathologic
      features of islet cell tumors with regard to tumor size, necrosis and cysts,
      calcification, malignant behavior, and functional status. MATERIALS AND METHODS:
      We retrospectively reviewed the clinical, pathologic, and imaging features of all
      133 cases of pathologically proved islet cell tumors of the pancreas seen at the
      Armed Forces Institute of Pathology. Clinical data, including the patients'
      symptoms and serologic characteristics, were used to distinguish hyperfunctioning
      tumors (those causing symptoms related to elevated serum polypeptide levels) from
      nonhyperfunctioning tumors; hyperfunctioning tumors were divided further into
      insulin-producing and non-insulin-producing types. All patients had at least one
      cross-sectional imaging study, including CT (n = 118), sonography (n = 42), or MR
      imaging (n = 22). Clinical, pathologic, and imaging features were evaluated and
      correlated with tumor size, necrosis and cysts, calcification, local invasion,
      vascular invasion, metastases, and functional status. RESULTS: Islet cell tumors
      with areas of necrosis or cystic change found pathologically and on imaging
      studies (56/133) were larger (8.4 cm in mean transverse diameter) than
      homogeneous solid lesions (2.9 cm in mean transverse diameter) and were
      predominantly non-insulin producing (48/56) and nonhyperfunctioning (36/56). Of
      the 43 insulinomas, 35 were small (2.2 cm in mean transverse diameter), solid,
      and homogeneous. Larger size also was associated with calcification and malignant
      behavior, including local invasion, vascular invasion, and distant metastases.
      CONCLUSION: Our findings show that cystic and necrotic islet cell tumors are
      usually non-insulin-producing and nonhyperfunctioning neoplasms and larger than
      the typically solid and small insulinomas. Calcification, local invasion,
      vascular invasion, and metastatic disease are more commonly seen with larger
      neoplasms.

PMID- 7572499
TI  - Endoscopic retrograde pancreatography: imaging findings.
AB  - Endoscopic retrograde pancreatography (ERP) is commonly used in the diagnosis and
      management of pancreatic disorders. The aim of this pictorial essay is to provide
      an overview of the common appearances of normal anatomy, anatomic variants, and
      pancreatic diseases at ERP.

PMID- 7572500
TI  - Value of CT in the diagnosis and management of patients with suspected acute
      small-bowel obstruction.
AB  - OBJECTIVE: The purpose of this prospective study was to evaluate the role of CT
      in the diagnosis of patients with suspected acute small-bowel obstruction in whom
      clinical and plain radiographic findings were inconclusive. SUBJECTS AND METHODS:
      Fifty-seven nonconsecutive patients with suspected acute small-bowel obstruction
      were referred for CT to differentiate small-bowel obstruction from ileus (33
      patients) or to establish the cause of obstruction (24 patients). The final
      diagnosis was established either by surgery (42 patients) or by the clinical
      evolution (15 patients). The change in the prescan diagnosis as to the presence,
      cause, and severity (strangulation) of small-bowel obstruction made on the basis
      of the CT findings was noted. Finally, the changes in therapy resulting from the
      CT information were recorded. RESULTS: CT correctly distinguished between small
      bowel obstruction and ileus in all cases except one. CT enabled us to modify an
      erroneous clinical diagnosis correctly in 12 (21%) of 57 cases, including eight
      cases for which pre-CT diagnosis was ileus and four cases for which pre-CT
      diagnosis was small-bowel obstruction. CT allowed us to predict the cause of
      obstruction correctly in 33 (85%) of 39 patients with confirmed small-bowel
      obstruction but it failed to differentiate adhesions from internal hernias and
      radiation enteritis. The pre-CT diagnosis of the cause of obstruction was
      correctly changed because of CT findings in 17 (44%) of 39 patients with
      subsequently proved small-bowel obstruction. CT was able to identify
      strangulation in nine of the 12 patients with proved strangulation, which altered
      the pre-CT diagnosis in three patients. CT findings correctly modified the
      management in 12 (21%) of 57 patients, by changing either a conservative
      management to an operative one in 10 (18%), or an operative to a conservative one
      by differentiating ileus from obstruction in two patients. CONCLUSION: Our
      findings show that CT is a valuable diagnostic procedure in patients with
      suspected acute small-bowel obstruction. CT not only is useful in distinguishing
      obstruction from paralytic ileus, but it frequently establishes the cause of the
      obstruction and the presence of strangulation. CT findings lead to decisions to
      treat patients surgically in a significant number of patients.

PMID- 7572501
TI  - Laparoscopic sonography during abdominal laparoscopic surgery: technique and
      imaging findings.
AB  - Laparoscopy is becoming the preferred approach for managing several abdominal
      disorders. The main limitations of laparoscopic surgery and diagnostic
      laparoscopy are the loss of the surgeon's tactile feedback and the inability to
      undertake a complete internal evaluation of solid parenchyma. Probes for
      laparoscopic sonography have been introduced to compensate for the limitations of
      laparoscopic surgery and to increase the diagnostic efficacy of laparoscopy [1].
      In this article we describe our experience with laparoscopic sonography and
      illustrate the normal anatomic findings and some applications in biliary surgery
      and other abdominal laparoscopic procedures.

PMID- 7572503
TI  - Frequency and significance of fractures of the upper cervical spine detected by
      CT in patients with severe neck trauma.
AB  - OBJECTIVE: Radiographic evaluation of the upper cervical spine in patients who
      have suffered severe trauma is often problematic because of the difficulty of
      obtaining adequate open-mouth views of the odontoid in these critically ill
      patients. This study was undertaken to determine the frequency and clinical
      significance of upper cervical spine fractures detected by CT in this patient
      population. MATERIALS AND METHODS: The study group consisted of 100 consecutive
      patients brought to the emergency department after severe trauma who had CT of
      the craniocervical junction done instead of an open-mouth view. Plain film
      evaluation consisted of a cross-table lateral view, an anteroposterior view, and,
      if necessary, a swimmer's view. The radiographic studies were reviewed
      retrospectively by a musculoskeletal radiologist and a neuroradiologist,
      respectively. Hospital records were reviewed to ascertain the patients' clinical
      signs and symptoms on admittance and to determine how identification of the
      fractures changed the treatment plan. RESULTS: Eight fractures in seven patients
      were identified with CT of the craniocervical junction. Three of the fractures
      were of the occipital condyle, and five were at the C1-C2 level. None of the
      fractures were seen directly on plain radiographs, although secondary signs of
      injury such as prevertebral soft-tissue swelling were seen in two of the seven
      cases. CONCLUSION: CT of the craniocervical junction revealed an 8% frequency of
      fractures of the occipital condyle and C1-C2 that were undetected on the cross
      table lateral cervical spine radiographs. Fractures occurred in greater numbers
      than expected, and all surviving patients were stabilized with a halo. This
      experience shows that CT is an efficient method of evaluating patients in whom
      the standard open-mouth radiograph of the odontoid cannot be done.

PMID- 7572502
TI  - Priapism caused by a perineal abscess in a patient with Crohn's disease: CT
      findings.

PMID- 7572505
TI  - Osteosarcoma: subtle, rare, and misleading plain film features.
AB  - Osteosarcoma is a malignant, mesenchymal, osteoid, and bone-forming tumor [1-3].
      In most cases, typical radiographic features clearly illustrate the aggressive
      bone-forming nature of the lesion. These features include long-bone metaphyseal
      location, mixed areas of lysis and sclerosis, cortical destruction, periosteal
      new bone, and soft-tissue mass. However, numerous factors contribute to
      misleading radiographic patterns of osteosarcoma. They include histologic low
      grade, lytic, or minimally sclerotic lesions, early detection, confinement to the
      intramedullary canal, benign-appearing periosteal reaction, rare intraosseous
      locations (subchondral, diaphyseal, intracortical), and rare skeletal sites
      (e.g., soft tissues, skull, ribs, tarsal bones). Secondary osteosarcomas, such as
      those arising from infarcts or fibrous dysplasia, may also produce a confusing
      radiologic picture. The purpose of this pictorial essay is to illustrate cases of
      osteosarcoma that proved to be difficult diagnostic dilemmas because of their
      subtle, rare, or misleading plain film features.

PMID- 7572504
TI  - Fractures of the vertebrae with spinal cord injuries in patients with ankylosing
      spondylitis: imaging findings.
AB  - Ankylosing spondylitis is a systemic rheumatologic disorder of adults that
      results in disease-specific inflammation and eventual ossification at the site of
      ligamentous insertion into bone. The resulting spinal ankylosis causes
      biomechanical alterations that predispose the patient to serious spinal injury
      even in the presence of minor trauma. With the loss of spinal flexibility and
      increased bone fragility, there is a propensity for vertebral fracture,
      instability, and increased neurologic complications. Illustrative examples of the
      imaging modalities are presented, as they contribute to the detection of
      fractures and spinal cord injuries in patients with ankylosing spondylitis.

PMID- 7572506
TI  - Traumatic anterior dislocation of the hip: spectrum of plain film and CT
      findings.
AB  - Traumatic anterior dislocation of the hip represents 11% of all hip dislocations
      and is classified into superior and inferior types [1]. Whereas inferior anterior
      hip dislocation is easily recognized on an anteroposterior radiograph of the
      pelvis, the radiographic appearance of superior anterior hip dislocation is less
      straightforward, often leading to an initial misdiagnosis of posterior hip
      dislocation. Misdiagnosis of the direction (anterior versus posterior) of a hip
      dislocation can result in failed closed reduction or an improper surgical
      approach to open reduction. In addition, recognition of associated impaction
      fractures is important, as patients with this finding have a greater tendency to
      develop traumatic arthritis [2, 3]. This pictorial essay, which is based on our
      experience with 20 cases of anterior hip dislocation, including five of the rare
      superior type, illustrates the spectrum of radiographic findings and
      distinguishing features associated with anterior hip dislocation.

PMID- 7572507
TI  - Tensor fasciae suralis: depiction on MR images.

PMID- 7572508
TI  - Normal age-related conversion of bone marrow in the mandible: MR imaging
      findings.
AB  - OBJECTIVE: The mandible is one of the most common sites for osteomyelitis and
      other marrow-based diseases. Therefore, knowledge of the normal patterns of
      marrow distribution could help evaluate marrow-based diseases. The purpose of
      this study was to assess the age-related normal sequence of conversion from
      hematopoietic to fatty marrow in the mandible as depicted on MR images. SUBJECTS
      AND METHODS: We prospectively reviewed T1-weighted MR images of the mandible for
      the distribution of hematopoietic and fatty marrow. Forty-five subjects 4 months
      to 25 years old with no known marrow abnormality were examined with the spin-echo
      technique. Marrow conversion was assessed in the condyle, ramus, angle, and body
      of the mandible using visual grading based on homogeneity, signal intensity, and
      a signal-intensity ratio determined by the intensities of the surrounding
      subcutaneous fat and air. RESULTS: Conversion of hematopoietic to fatty marrow
      occurred first in the mandibular body, followed by the angle, ramus, and finally
      the condyle. The marrow in the region distal to the ramus had almost fully
      converted to fatty marrow by the third decade of life, but the remaining regions
      contained some hematopoietic marrow. Further substantiating these results, the
      signal-intensity ratio increased up to about 90% in the angle and 70% in the
      ramus by the age of 10 years and then leveled off. On the other hand, the signal
      intensity ratio in the condyle reached 60% by age 15 and remained unchanged for
      the following 10 years. CONCLUSION: The normal age-related conversion from
      hematopoietic to fatty marrow in the mandible follows a well-defined sequence,
      first seen in the mental region early in childhood, then in the body, the ramus,
      and finally the condyle.

PMID- 7572510
TI  - Evaluation of normal and abnormal lips in fetuses: comparison between three- and
      two-dimensional sonography.
AB  - OBJECTIVE: The purpose of this study was to determine if three-dimensional (3D)
      sonography could improve prenatal evaluation of fetal lips in comparison with
      conventional two-dimensional (2D) sonography. MATERIALS AND METHODS: Sixty-one
      high-risk pregnant women and 10 low-risk pregnant women were examined with
      conventional 2D sonography followed by 3D sonography with a volume transducer.
      The ability to visualize cleft lips and normal lips was compared between the two
      techniques. RESULTS: Of the 71 fetuses studied, faces were seen in 68 and not
      seen in three by either 2D or 3D sonography. Abnormal lips were seen in five
      fetuses on both 2D and 3D sonograms. Of the remaining fetuses, 3D sonography was
      able to confirm the presence of a normal lip in 92% (58/63) compared with 76%
      (48/63) with 2D sonography. In the subgroup of fetuses less than 24 weeks'
      estimated gestational age, 3D sonography confirmed a normal lip in 93% (38/41) of
      fetuses as compared with 68% (28/41) for 2D sonography. There was no difference
      between 3D and 2D in the subgroup of fetuses older than 24 weeks. One false
      positive finding of cleft lip was observed at 36 weeks' gestational age with the
      rendered surface display on 3D sonography, whereas the 3D planar views of the
      same volume showed the lips to be normal. CONCLUSION: 3D sonography was able to
      confirm the presence of normal lips more frequently than did 2D sonography in
      fetuses less than 24 weeks' gestational age. Abnormal lips were seen on both 2D
      and 3D sonograms; however, 3D images of cleft lip were easier to understand for
      both the family and clinical colleagues.

PMID- 7572509
TI  - Fluoroscopic diagnosis of laryngeal asthma (paradoxical vocal cord motion).

PMID- 7572512
TI  - Intracranial subependymomas: CT and MR imaging features in 24 cases.
AB  - OBJECTIVE: The intracranial subependymoma is a benign glioma that has been
      classically described as an asymptomatic fourth ventricular tumor found
      incidentally at autopsy in elderly men. The purpose of this study was to
      characterize the differences in CT and MR imaging appearances between
      subependymomas of the fourth and lateral ventricles, both of which were found in
      symptomatic patients. MATERIALS AND METHODS: We retrospectively reviewed 24
      pathologically proved cases of intracranial subependymomas in 17 male and seven
      female patients with a mean age of 48.1 years. All patients were symptomatic. CT
      and MR images were used to characterize the size, shape, and location of the
      subependymomas; the degree of hydrocephalus; tumor calcification; and the
      density, signal, and enhancement characteristics of the tumors. RESULTS: Eighteen
      of 24 tumors were 3 cm or more in greatest dimension. Nineteen were lobulated,
      and hydrocephalus was seen in 21. Fourteen were in the lateral ventricle, and 10
      were in the posterior fossa. Calcifications were present in five (all fourth
      ventricular) and absent in 10 (all lateral ventricular) subependymomas imaged
      with unenhanced CT. On 18 contrast-enhanced CT scans, five of six subependymomas
      with heterogeneous enhancement were in the fourth ventricle, and nine of 12
      tumors with minimal or no enhancement were in the lateral ventricle. Small
      internal foci with a signal intensity similar to that of CSF were seen on images
      of all 10 lateral ventricular subependymomas obtained with both T1-weighted and
      T2-weighted sequences. On 13 contrast-enhanced T1-weighted images, seven of eight
      tumors with heterogeneous enhancement were in the fourth ventricle, and all five
      with minimal or no enhancement were in the lateral ventricle. CONCLUSION:
      Intracranial subependymomas were seen in symptomatic middle-aged adults and
      showed different CT and MR imaging features, depending on their anatomic
      location. Calcification and heterogeneous contrast enhancement were common
      features of fourth ventricular subependymomas showed a lack of calcification as
      well as minimal or no contrast enhancement of CT and MR images.

PMID- 7572511
TI  - Abnormalities of the hands and feet in the fetus: sonographic findings.
AB  - This pictorial essay illustrates abnormalities of the hands and feet that
      sonography depicts and describes their associations with chromosomal
      abnormalities, syndromes, and other pathology. Examination of the extremities,
      although not listed in the guidelines of the American Institute of Ultrasound in
      Medicine for standard obstetric sonography, is a critical adjunct to fetal
      imaging and is needed to diagnose many syndromes. Anomalies of the hands and feet
      may involve all limbs or be focal, involving a single distal ray. Although this
      essay focuses on defects of the hands and feet, these defects are often part of
      more global defects that include the rest of the limb as well. For this reason,
      anomalies of the limbs that relate primarily to defects of the hands and feet
      will also be demonstrated. Evaluation of the hands and feet is an important part
      of the structural survey of the fetus at all gestational ages, as it provides an
      adjunct to the diagnosis of many syndromes, including chromosomal abnormalities.
      Even isolated limb anomalies may be important to diagnose antenatally so that
      proper care can be instituted postnatally for families and their newborns.

PMID- 7572513
TI  - Contrast-enhanced MR angiography for the diagnosis of intracranial vascular
      disease: optimal dose of gadopentetate dimeglumine.
AB  - OBJECTIVE: Although contrast-enhanced MR angiography has been shown useful in
      evaluating intracranial vascular lesions, particularly those with slow flow, the
      optimal dose of contrast material has not been found. Accordingly, we performed a
      study to determine the optimal dose of gadopentetate dimeglumine for contrast
      enhanced MR angiography of intracranial vascular diseases. SUBJECTS AND METHODS:
      In this prospective study, 152 consecutive adult patients suspected of having
      intracranial vascular diseases had cerebral MR angiograms. Images were obtained
      with a three-dimensional time-of-flight sequence with magnetization transfer
      saturation on a 1.5-T unit. Imaging parameters (43/8 [TR/TE], 20 degrees flip
      angle, 64 1-mm-thick sections) were identical in each MR angiogram. One hundred
      twenty-two of 152 patients were randomly assigned to receive one of four doses
      (0, 5, 10, or 20 ml) of gadopentetate dimeglumine for MR angiography (36, 37, 38,
      and 11 patients, respectively). In patients who had normal major cerebral
      arteries on MR angiograms, degree and extent of visualization of the cerebral
      veins and small intracranial arteries were rated blindly on a three-point scale,
      and the results were compared among the four groups given different doses of
      contrast material. In another 30 patients who had unenhanced and enhanced MR
      angiograms, the presence or absence of artifactual narrowing of the internal
      carotid artery or major cerebral arteries (caused by signal loss due to slow or
      turbulent flow seen only on unenhanced images) and the visibility of
      arteriovenous malformation were determined. RESULTS: In nearly all patients,
      regardless of the dose of contrast material, the cerebral veins were well
      visualized on MR images. Degree and extent of visualization of the cerebral veins
      appeared to depend on the dose of contrast material. In the 20-ml injection
      group, venous overlap limited interpretation of the small and large arteries,
      whereas in the 5- and 10-ml groups, the signal intensity of the veins was much
      less intense, causing no difficulty in interpretation. However, no significant
      differences in visibility of the small arteries were apparent between the
      unenhanced and enhanced MR angiograms, even though the small vessels were better
      visualized in some patients who received either 5 or 10 ml of contrast material.
      In six of the 30 patients who had both unenhanced and enhanced MR angiograms, the
      unenhanced images showed artifactual narrowing of the internal carotid or middle
      cerebral arteries, which proved to be normal on contrast-enhanced MR angiograms.
      Venous sinuses or draining veins were better delineated on contrast-enhanced MR
      angiograms in all six patients with arteriovenous malformation. CONCLUSION: Five
      to 10 milliliters of gadopentetate dimeglumine appears to be an optimal dose
      range for contrast-enhanced cerebral MR angiography. Use of this dose can help in
      differentiating true stenosis of large arteries from artifactual narrowing and in
      depicting small arteriovenous malformation with slow flow.

PMID- 7572515
TI  - MR imaging of myxopapillary ependymoma: findings and value to determine extent of
      tumor and its relation to intraspinal structures.
AB  - OBJECTIVE: Myxopapillary ependymomas are highly vascular tumors that arise almost
      exclusively in the thoracolumbar region and produce symptoms that may mimic
      discogenic pathology. The purpose of our study was to define the typical MR
      features of myxopapillary ependymoma and to determine the value of MR imaging in
      identifying the tumor, establishing its extent, and defining its relationship to
      intraspinal structures. MATERIALS AND METHODS: MR studies performed on 20
      patients (13 men and seven women; mean age, 35 years) with 24 pathologically
      proven myxopapillary ependymomas were evaluated retrospectively for size and
      location of lesions, expansion of the central spinal canal and neural foramina,
      and MR signal characteristics and enhancement patterns. T1-weighted (16
      patients), proton density-weighted (15 patients), T2-weighted (14 patients), and
      enhanced T1-weighted (nine patients) sequences were examined. RESULTS: In all
      patients, masses were detected on MR images. MR imaging defined solitary masses
      in 17 patients and multiple lesions in three. Of the 24 tumors, MR imaging
      characterized 21 as predominately intradural extramedullary, two as
      intramedullary and intradural extramedullary, and one as extradural postsacral.
      Two lesions had associated syrinxes. Lesions occurred most often at the level of
      the L2 vertebral body, and no tumor extended above T9. Tumors spanned an average
      of four vertebral segments. MR imaging showed expansion of the spinal canal in
      five of eight tumors that extended over five or more vertebral segments. Two
      tumors extended into the neural foramina. The T1-weighted signal of the tumor was
      isointense in 12 patients, hypointense in three patients, and hyperintense in one
      patient. The T2-weighted signal was always hyperintense. All tumors imaged after
      administration of IV contrast material showed enhancement. CONCLUSION: MR imaging
      was valuable in identifying the extent of tumors and in defining their
      relationship to the intraspinal structures. Although the MR findings in
      myxopapillary ependymoma are nonspecific, the diagnosis can be suggested by a
      large, intensely enhancing, intradural extramedullary thoracolumbar mass that
      extends for several vertebral levels. Imaging protocols should examine the entire
      thoracolumbar region and include IV contrast.

PMID- 7572514
TI  - MR diagnosis of subacute and chronic subarachnoid hemorrhage: comparison with CT.
AB  - OBJECTIVE: The purpose of our study was to compare the value of MR imaging with
      CT in the diagnosis of subarachnoid hemorrhage in the subacute and chronic stages
      (> 3 days after the hemorrhagic episode). MATERIALS AND METHODS: We performed 42
      MR examinations using a 0.5-T unit in 37 patients with subarachnoid hemorrhage
      caused by a ruptured aneurysm. Examinations were done 4-75 days after the ictus.
      We obtained 40 T1-weighted, 11 proton density-weighted, 15 T2-weighted, and 28
      moderately T2-weighted images. CT was also performed in all patients within 24 hr
      of the MR examination. Confirmation of the presence of subarachnoid hemorrhage at
      the time of the MR examination was made by CSF examination using lumbar puncture
      or surgical findings. RESULTS: In the subacute and chronic stages, subarachnoid
      hemorrhage was seen as an area of high signal intensity on T1-weighted, proton
      density-weighted, T2-weighted, and moderately T2-weighted MR images in 63%, 90%,
      25%, and 92% of cases, respectively. On CT scans, subarachnoid hemorrhage was
      seen as an area of high attenuation in only 46% of cases. Especially in the
      chronic stage, subarachnoid hemorrhage was seen as an area of high signal
      intensity more frequently by MR imaging than by CT (90% on T1-weighted images;
      100% on proton density-weighted images; 25% on T2-weighted images; 100% on
      moderately T2-weighted images; and 10% on CT scans). High-signal-intensity
      subarachnoid hemorrhage was demonstrated by MR imaging until a maximum of 39 days
      after the ictus, whereas high-attenuation subarachnoid hemorrhage was
      demonstrated by CT until a maximum of 17 days after the ictus. CONCLUSIONS: Our
      findings show that MR imaging is superior to CT for the diagnosis of subacute and
      chronic subarachnoid hemorrhage. MR imaging is especially useful for the
      diagnosis of chronic subarachnoid hemorrhage.

PMID- 7572516
TI  - Superselective intraarterial infusion of cisplatin for squamous cell carcinoma of
      the mouth: preliminary clinical experience.
AB  - OBJECTIVE: The purpose of this study was to assess the initial clinical response
      to superselective intraarterial infusion of cisplatin for treating stage III and
      stage IV squamous cell carcinoma of the mouth. SUBJECTS AND METHODS: Thirteen
      patients received intraarterial cisplatin therapy. The tumors were located in the
      tongue (n = 7), gingiva (n = 3), buccal mucosa (n = 1), hard palate (n = 1), and
      floor of the mouth (n = 1). A coaxial technique was used to place microcatheters
      in the lingual, facial, inferior alveolar, buccinator, and distal internal
      maxillary arteries, depending on tumor location. The feeding vessels were
      identified by staining the tumor with infusion of indigocarmine dye in the
      selected vessel. Relatively low-dose cisplatin (30-40 mg/m2) was injected at the
      rate of 50 mg/hr. Two or three injections were performed, with a 1-week interval
      between injections. After chemotherapy, eight patients underwent surgery, four
      had radiation therapy, and one had both. RESULTS: Thirty-four intraarterial
      infusions were done successfully without any complications. Arterial infusion of
      indigocarmine dye was useful for exact identification of feeding vessels,
      especially when the tumor was extensive, at the margin of the arterial supply, or
      near the midline. The overall response rate was 92% (complete response [tumor
      completely resolved], 38%; partial response [tumor reduction > or = 50%], 54%).
      Ten of 13 patients had no recurrence from 4 to 19 months (mean, 10 months) after
      treatment. Two patients died of metastatic diseases 6 months after surgery or
      radiation therapy. One patient had local recurrence 8 months after surgery and
      postoperative irradiation. No systemic toxicity such as renal failure, liver
      dysfunction, or bone marrow suppression was observed. Mild and transient local
      toxicity such as edema or mucositis of the infused area was relatively common.
      Trigeminal neuralgialike symptoms and reduced mouth opening occurred in two cases
      and one case, respectively, probably due to direct toxicity to the peripheral
      trigeminal nerve and masticatory muscles, respectively. CONCLUSION:
      Superselective intraarterial infusion of low-dose cisplatin is feasible and safe
      and may have important applications in treating advanced carcinoma of the mouth.

PMID- 7572519
TI  - Operator errors during percutaneous placement of vena cava filters.
AB  - Operator errors during percutaneous insertion of inferior vena cava (IVC) filters
      are procedural complications specific to filter placement that cannot be
      attributed to defects in the device itself. These errors can occur during
      preplacement imaging of the IVC, selection of the filter, or deployment of the
      filter. Although technical problems are reported to occur in 5-20% [1] of filter
      insertions, the precise frequency of operator errors is not known. This pictorial
      essay reviews the different types of operator errors that can occur during
      percutaneous insertion of IVC filters.

PMID- 7572517
TI  - Oral-maxillary sinus fistula (oroantral fistula): clinical features and findings
      on multiplanar CT.
AB  - OBJECTIVE: Oroantral fistula, an abnormal communication between the oral cavity
      and the maxillary sinus, is infrequently diagnosed radiologically. The purpose of
      this study was to describe the CT findings and clinical features of oroantral
      fistula and to show that dental CT multiplanar reformatting programs can be
      instrumental in diagnosing this condition. SUBJECTS AND METHODS: The study
      included eight patients with clinically confirmed oroantral fistula or with
      radiologic evidence of oroantral fistula. Fistula size, degree of alveolar
      atrophy, nature of maxillary sinus disease, and related dental disease were
      assessed along with the clinical presentations. RESULTS: The most frequent CT
      findings were bony discontinuity of the maxillary sinus floor, communication
      between the oral cavity and the sinus, soft-tissue opacification of the
      ipsilateral maxillary sinus, focal areas of alveolar atrophy, and associated
      periodontal disease. In 6 of 8 patients there was 100% opacification of the
      ipsilateral maxillary sinus, and in 5 of 8 patients the contralateral sinus
      appeared completely normal. The fistula size ranged from 13.5 mm2 to 189 mm2.
      CONCLUSION: The appearance of oroantral fistula on multiplanar CT imaging is
      disruption of the bony floor of the maxillary sinus with soft-tissue
      opacification of the ipsilateral sinus. Dental reformatted CT can be useful for
      evaluating patients suspected of having oroantral fistula, and this condition may
      be found incidentally in patients referred for evaluation for osseointegrated
      root-form dental implants.

PMID- 7572518
TI  - Cytopathologic touch preparations (imprints) from core needle biopsies: accuracy
      compared with that of fine-needle aspirates.
AB  - OBJECTIVE: The aim of this study was to evaluate the touch preparation (imprint)
      cytology method for obtaining rapid interpretations from core material obtained
      during abdominal percutaneous biopsy. SUBJECTS AND METHODS: For 28 patients
      undergoing biopsy of abdominal masses, paired slides were prepared for rapid
      staining by use of smears of standard fine-needle aspirates and by use of a touch
      preparation of the core material obtained with a semiautomated biopsy gun. The
      slides were scored in comparison with the final cytopathologic and
      histopathologic diagnosis. RESULTS: Touch preparation slides were equivalent in
      diagnostic yield to fine-needle aspirate smears, demonstrating similar cellular
      features. Touch preparation slides revealed features of tumor architecture not
      present on smears. CONCLUSION: Touch preparation cytology offers rapid diagnosis
      from a single core biopsy sample. Carefully performed, the touch preparation
      method preserves the core material for subsequent permanent fixation and
      sectioning.

PMID- 7572520
TI  - Spontaneous dissection of the celiac and hepatic arteries treated by
      transcatheter embolization.

PMID- 7572521
TI  - Contrast-enhanced three-dimensional MR angiography in a single breath-hold: a
      novel technique.

PMID- 7572522
TI  - Off-hours interpretation of radiologic images of patients admitted to the
      emergency department: efficacy of teleradiology.
AB  - OBJECTIVE: The purpose of our study was to assess the efficacy of a commercially
      available digital teleradiology system in the off-site interpretation of
      radiologic studies performed in the emergency department. MATERIALS AND METHODS:
      Over a 6-month period, all radiologic studies performed at Roosevelt Hospital
      between the hours of midnight and 8 A.M. were digitized and then transmitted over
      a T1 fiberoptic link to the radiology department of St. Luke's Hospital, 4.8 km
      away. A total of 829 radiologic examinations were performed, 17 of which were
      lost to follow-up, leaving 812 studies available for review (693 plain
      radiographs, 118 CT exams, and one MR imaging study). The preliminary
      teleradiology interpretations were performed by a resident on duty (with between
      1 and 3.5 years of training) using a commercially available teleradiology system
      (Vortech PDS; Kodak Health Imaging Systems Inc., Dallas, TX) at St. Luke's
      Hospital. This interpretation was compared with the official film interpretation
      (which was used as the gold standard) performed within 24 hr by a board-certified
      attending radiologist at Roosevelt Hospital. All studies with clinically
      significant discrepant interpretations were redigitized, and the digital images
      were reviewed by at least two attending radiologists. Side-by-side comparison was
      made with the original analog examinations to determine the source of the
      discrepancy. Discrepant images were then graded in conjunction with an attending
      physician from the emergency department to determine the clinical impact on
      patient management. RESULTS: Clinically significant discrepancies (those with the
      potential to affect patient management) in image interpretation were found in 38
      cases (5% of the total). Of these 38 cases, three cases (0.4%) were due to an
      inadequate digital image while 14 (2%) were due to interobserver error. Two
      (0.2%) discrepancies were due to film reader error, and 19 (2%) were due to
      digital image reader error. Reasons for inadequate digital images included
      underpenetrated radiographs and drifting of the laser digitizer. CONCLUSION:
      Commercially available teleradiology equipment can be both reliably and
      effectively used for off-hours interpretation of radiologic studies made in the
      emergency department.

PMID- 7572523
TI  - With the high cost of nonionic contrast media, it has been suggested that we use
      a plain abdominal radiograph (KUB) and renal sonography to evaluate patients with
      hematuria.

PMID- 7572524
TI  - Define the appropriate use of enteroclysis in managing patients.

PMID- 7572525
TI  - How should patients be evaluated radiographically who have microscopic hematuria
      after blunt trauma to the abdomen?

PMID- 7572526
TI  - What is the role of fine needle biopsy in the diagnosis of lymphoma?

PMID- 7572527
TI  - What is the tardus parvus spectral Doppler waveform, and what is its usefulness
      in the detection of hepatic or renal artery stenosis?

PMID- 7572528
TI  - A serpiginous intradural filling defect on a lumbar myelogram could be identified
      as a spinal dural arteriovenous fistula or a spinal arteriovenous malformation.

PMID- 7572529
TI  - The last radiologist: a response to Dr. Rosenquist.

PMID- 7572530
TI  - Hilar pseudonodule due to varix of the inferior pulmonary vein.

PMID- 7572531
TI  - Malignant pericardial effusion: percutaneous creation of a pericardial window.

PMID- 7572532
TI  - Re: Electron-beam CT demonstration of a right ventricular myxoma in an infant.

PMID- 7572533
TI  - CT of the gastrointestinal tract.

PMID- 7572534
TI  - A plea for narrow windows.

PMID- 7572535
TI  - Enhancement or not?

PMID- 7572536
TI  - Thickening of the transverse colon associated with torsion of the greater
      omentum.

PMID- 7572537
TI  - Measures for measurements: analog measurements on digital hard copies.

PMID- 7572538
TI  - [Prevalence of sensitization to Blomia in Gran Canaria].
AB  - In the present study we assessed the prevalence of sensitizations to Blomia in
      our environment. Perennial climatological conditions in the Canarian Islands
      facilitates the habitat to mites. The Blomia is found in tropical and subtropical
      homes of Europe, USA and Asia like the Dermatophagoides. We have designed a
      transversal and prospective study on 100 patients who consulted our Unit for the
      first time. A Prick-test for the common allergens, including Blomia Kulagini, and
      in vitro determination of total and specific IgE to Dermatophagoides
      Pteronyssinus and Farinae, was performed in those patients showing the same or
      higher levels than class 3 CAP System RAST-Fesa against Blomia Tropicalis.
      Results achieved in our environment and our patients are the following: 1.
      Prevalence of sensitizations to BK in patients who consult for the first time is
      50%. 2. The specific IgE immunologic response to BK is 56% (45 patients). 3.
      Scarce correlation in the papule areas and specific IgE levels between BT and DTP
      (p = 0.22020); BT and DFA (p = 0.09063). Table VI. Fig. I and II. 4. These
      results and previous studies of allergenization suggest poor crossed reactivity
      between Blomia and Dermatophagoides. 5. We think that Blomia is a new etilogic
      agent of the allergic respiratory disorders in our environment and therefore it
      should be included in the standard set of allergens from a diagnostic and
      therapeutical point of view. We keep studying its identification and count in
      dust samples from our homes, as well as the crossed reactivity, by RAST
      inhibition, with other acari.

PMID- 7572539
TI  - Changes in nasal metachromatic cells during allergen immunotherapy in children.
AB  - Immunotherapy (IT) has been successfully used in the treatment of allergic
      rhinitis for years. Several mechanisms have been postulated for the clinical
      efficacy of IT. In this study we investigated the effect of IT on the number of
      metachromatic cells on the nasal surface in children with perennial allergic
      rhinitis (PAR). Nineteen subjects were treated with IT and 12 subjects, who did
      not receive any treatment, constituted the 3rd and 6th months of IT by symptom
      scores, physical examination findings, metachromatic cell counts from nasal
      mucosal epithelial scrapings and nasal provocation scores. At the 3rd and 6th
      months of IT, nasal symptom scores, nasal provocation scores and the number of
      metachromatic cells in epithelial scrapings were significantly reduced compared
      with the pretreatment values in the IT group. These reductions were not observed
      in the control group. It is concluded that the reduction in the number of
      metachromatic cells could be at least partially responsible for the clinical
      efficacy of IT in children with PAR.

PMID- 7572540
TI  - Analysis of zinc, iron and copper serum levels in patients with common variable
      immunodeficiency.
AB  - Serum zinc, copper and iron levels together with content of zinc in hair were
      investigated in 13 patients with common variable immunodeficiency (CVID) and in
      13 controls. A significant decrease in serum zinc (mean = 11.3 mumol/l, SD = 2.9
      in CVID patients compared to mean 14.3 mumol/l, SD = 2.4 in controls) and iron
      levels (mean = 11.8 mumol/l, SD = 3.1 in CVID patients, mean = 18.3 mumol/l, SD =
      4.7 in controls) in CVID patients were observed. Hair zinc content of CVID
      patients was significantly decreased compared to healthy persons (1.41 mumol/g,
      SD = 0.64 in CVID patients, and mean = 2.23 mumol/g, SD = 0.83 in controls).
      Serum copper level in CVID patients was significantly increased compared to
      controls (mean = 24.4 mumol/l, SD = 4.8 in CVID Patients, mean = 14.6 mumol/l, SD
      = 2.8 in controls). The decreased serum zinc and iron levels may be caused by
      disturbed absorption in the intestines of patients with CVID, but redistribution
      due to chronic inflammatory processes is a second possible explanation of
      hypozincemia in CVID patients.

PMID- 7572541
TI  - Prick and intradermal tests compared with specific IgE in allergic assessment.
AB  - Allergic assessment in symptomatic patients often requires more tests and they
      can be conflicting. Sixty outpatients, suffering from seasonal or periannal
      respiratory symptoms, underwent prick tests, intradermal reactions and specific
      IgE (IgEs) determination by enzime immunoassay for eight common allergens; in
      addition total IgE were measured. At the end of the study 512 tests were
      performed. Total serum IgE levels had no significance in the results. There was a
      statistically different behaviour among three methods; a positive or negative
      concordance was found in 64.1% of tests whereas in the others (35.9%) results
      were conflicting. In particular it was seen that a prick test positive was
      confirmed by intradermal reaction and a test prick and intradermal negative was
      not probably confirmed by IgEs. Serum specific IgE levels were higher in subjects
      prick and intradermal positive than in prick negative and intradermal or IgEs
      positive subjects. Intradermal reactions were found positive especially in mites
      and often they were not confirmed by prick or IgEs. So prick test is always the
      routine test; intradermal test ought to be used if there were prick tests
      negative and patient's history positive. If prick and intradermal test were found
      negative it is plausible that the measurement of specific IgE will be negative
      circumscribing even more the number of individuals where determination of serum
      specific antibody is necessary.

PMID- 7572543
TI  - [Anaphylaxis caused by royal jelly].
AB  - Royal jelly is the food on which are fed and which causes them to develop into
      queen bees. It is claimed to have rejuvenating virtues for human beings. This
      report describes a 15-year-old atopic woman who presented, 15 minutes after the
      intake of royal jelly, local angioedema, generalised urticaria, dysphonia and
      bronchospasm. She was given antihistaminics and corticoesteroids and responded
      well. The ingested product contains royal jelly, lactose and potassium sorbate.
      No anaphylactic reactions to lactose and sorbates have been described previously.
      Prick test to common food allergens hymenoptera venoms and pollens were negative.
      RAST to meletin was also negative. Blood eosinophils were 600 and total IgE 465.
      Non-commercial prepared specific IgE to royal jelly was positive (0.8 KU/l).
      Prick by prick was positive to 1/10 dilution, being negative in controls
      (undiluted). No oral provocation test was performed due to the risk of
      anaphylaxis. No reported cases of royal jelly allergy were founded in a review of
      the medical literature. Concluding, it is the first described case of IgE
      anaphylactic reaction due to royal jelly.

PMID- 7572545
TI  - Serotonin syndrome: what family physicians need to know.

PMID- 7572542
TI  - Epidemiology of allergic reactions in beekeepers: a lower prevalence in subjects
      with more than 5 years exposure.
AB  - Beekeepers (Bks) represent a high allergic risk population against Hymenoptera
      because of their frequent exposure to bee stings. Most published studies show
      different percentage of sensitization and systemic reactions with to another
      groups of population. With the aim to know the prevalence and type of allergic
      reaction in Bks from the Canary Islands, 246 subjects were studied prospectively.
      A questionnaire was developed and skin test and specific IgE determination
      against Apis mellifera, Vespula and Polistes venom were performed. One hundred
      and twenty eight subjects had presented at least one reaction greater than merely
      local. In 83.5% of these subjects subsequent stings caused reactions of lesser
      intensity. Specific IgE in serum for Apis mellifera was positive in 126 BKs, for
      Vespula in 27 and for Polistes in 9. We found that the group of BKs sensitized to
      Apis was significantly higher among atopics BKs (p < 0.001) and with fewest years
      of working experience in beekeeping (p = 0.0134). This study showed that
      sensitization to Hymenoptera is higher in beekeepers with less than 5 years
      working experience and who are sensitized to another allergens.

PMID- 7572546
TI  - The need to identify smokeless tobacco users.

PMID- 7572547
TI  - Myositis associated with griseofulvin therapy.

PMID- 7572544
TI  - [Non-sedative antihistaminics in the treatment of chronic urticaria].
AB  - Antihistamines are the drugs of choice in the symptomatic relief of chronic
      idiopathic urticaria; however, the usefulness of classic antihistamines has been
      limited by side effects. In the 1980s a new class of antihistamines has been
      developed that maintains effectiveness and produces less side effects (eg
      anticholinergic side effects, daytime sedation, etc). This review analyzes each
      of the new nonsedating antihistamines commercially available in Spain
      (astemizole, ebastine, cetirizine, loratadine and terfenadine) and evaluates its
      clinical efficacy and safety in the treatment of chronic idiopathic urticaria.

PMID- 7572549
TI  - Acute internal bleeding as a cause of syncope.

PMID- 7572550
TI  - Low-dose antidepressant therapy for early depression.

PMID- 7572548
TI  - Sexual activity and recommendations for the hepatitis B vaccine.

PMID- 7572551
TI  - 'Dose dumping' and sustained-release theophylline.

PMID- 7572552
TI  - Advanced orthopedic consultation for hip replacement surgery.

PMID- 7572553
TI  - Diagnostic ultrasound skills for family physicians.

PMID- 7572554
TI  - Manifestations of onchocerciasis.

PMID- 7572555
TI  - Vertebrobasilar disease and beauty parlor stroke syndrome.

PMID- 7572556
TI  - Care at the twilight: ethics and end-of-life care.

PMID- 7572557
TI  - Diagnosis and management of low back pain and sciatica.
AB  - Acute low back pain with associated sciatica is usually a benign, self-limited
      disorder. Appropriate medical treatment may include passive forms of physical
      therapy, including McKenzie exercises, manipulation, medication and therapeutic
      injections. After pain is controlled, the patient should be taught self
      management techniques, including exercises and ergonomic protection of the spine.
      Evidence is increasing that exercise programs are effective, although the optimal
      regimen has yet to be defined and may vary from patient to patient. Chronic low
      back pain is a complex disorder that must be managed aggressively with a
      multidisciplinary approach that addresses physical, psychologic and socioeconomic
      aspects of the illness. Self-administered traction, corsets, medications and
      other treatment methods may prove to be useful adjuncts to an active program of
      exercise and education that promotes functional restoration.

PMID- 7572558
TI  - Palpable purpura: an algorithmic approach.
AB  - Cutaneous vasculitis, secondary to drug reaction, infection or collagen vascular
      disease, is the most common identifiable cause of palpable purpura. Common causes
      of palpable purpura often can be identified during the patient's history and
      physical examination. When this condition occurs in a patient who has not had a
      known precipitating event, or when the cause is unclear from the history and
      physical examination, diagnosis may be based on findings of the laboratory
      investigations and skin biopsy. Many cases of palpable purpura are idiopathic and
      self-limited. When treatment is necessary, dapsone, colchicine or systemic
      corticosteroids are useful drugs.

PMID- 7572560
TI  - The radiology of rheumatoid arthritis.
AB  - Rheumatoid arthritis is a connective tissue disorder of unknown etiology that can
      involve any synovial-lined joint in the body. The most frequently involved joints
      are the small joints of the hands and feet, the wrists, knees and elbows, and the
      glenohumeral and acromioclavicular joints. The radiographic hallmarks of
      rheumatoid arthritis are swelling of the soft tissue, osteoporosis, narrowing of
      the joint spaces and marginal erosions. The unique combination of osteoporosis,
      marginal erosions and relatively minimal reactive bone formation help distinguish
      rheumatoid arthritis from other inflammatory arthritides.

PMID- 7572559
TI  - Acquired digital fibrokeratoma.
AB  - Acquired digital fibrokeratomas are benign growths that usually occur on the
      fingers. These growths have a characteristic clinical and histopathologic
      appearance and may be easily recognized and treated by family physicians. It is
      important not to confuse these lesions with other common, possibly malignant,
      clinical entities. Treatment involves shave excision under local anesthesia.

PMID- 7572561
TI  - Fetal medicine: treating the unborn patient.
AB  - Fetal medicine is a rapidly growing discipline that combines the expertise of
      many specialties, including obstetrics, neonatology and pediatric surgery. The
      field is unique in that the physician rarely touches or sees the unborn patient
      directly. Thus, recent advances in ultrasonographic imaging (real-time and
      increased-resolution imaging) have played a pivotal role in the development of
      fetal diagnosis and therapy. Fetal access must take into account the safety of
      the mother and includes intra-amniotic, intracordal and fetal intramuscular
      routes. Medical treatment of the fetus includes exchange transfusion, thyroid
      hormone replacement and administration of steroids for surfactant induction.
      Correction of obstructive uropathy with urinary diversion has proved successful
      in decreasing fetal morbidity and mortality, while other procedures are still in
      the experimental stage. Extrauterine fetal surgery is performed only rarely but
      represents an exciting new direction in the treatment of medicine's youngest
      patients.

PMID- 7572562
TI  - Vasectomy counseling.
AB  - The following recommendations for counseling patients about vasectomy may help to
      minimize the risk of litigation for family physicians who provide vasectomy
      services: (1) conduct a personal consultation with the patient; (2) discuss the
      impact of vasectomy on sexual function; (3) explain the procedure using diagrams
      during the office visit for the physical examination; (4) explain possible minor
      complications and risks, including the possibility of failure; (5) explain the
      need for a postoperative semen analysis and the need to use another contraceptive
      method for a while after vasectomy; (6) emphasize the permanence of the
      procedure; (7) have the patient read and sign an informed consent form; (8)
      provide preoperative and postoperative instructions; (9) answer questions and
      respond to concerns, and (10) telephone the patient the day after the surgery.

PMID- 7572563
TI  - Febrile seizures: a decision-making analysis.
AB  - Febrile seizures are the most common type of seizures in childhood. Although
      febrile seizures may be frightening to observers, they are benign and do not
      cause death, neurologic damage, injury or learning disorders, and they rarely
      require medication. Parents of children who have febrile seizures, however,
      require considerable support, education and reassurance. Appropriate counseling
      by the physician requires knowledge of the natural history of febrile seizures.
      Treatment decisions should result from informed and appropriate decision-making
      about medication and potential risks.

PMID- 7572564
TI  - Vitreoretinal emergencies.
AB  - Emergencies that affect the visual system can be devastating, with loss of vision
      being the most feared complication. In addition, visual signs and symptoms may
      indicate the coexistence of systemic conditions that can result in stroke,
      myocardial infarction and death. In patients who present with sudden loss of
      central or peripheral vision or pain in or around the eye, a careful examination
      of the eye and adnexa is warranted. Traumatic injuries also necessitate a careful
      examination to locate treatable problems. Prompt evaluation and treatment of
      vitreoretinal emergencies are important in the preservation of vision. These
      conditions can result in loss of vision or other severe consequences, especially
      if they are not promptly evaluated and treated by an ophthalmologist specializing
      in vitreoretinal disorders.

PMID- 7572566
TI  - Hepatobiliary complications of inflammatory bowel disease.
AB  - Clinically significant liver and biliary disorders occur in approximately 5
      percent of persons with inflammatory bowel disease. The most common hepatobiliary
      disorders encountered in patients with inflammatory bowel disease are fatty
      liver, sclerosing cholangitis and gallstones. In addition, chronic hepatitis,
      cirrhosis, biliary cancer and amyloidosis sometimes occur. Family physicians
      should be alert for these gastrointestinal problems in patients with inflammatory
      bowel disease.

PMID- 7572565
TI  - Smokeless tobacco: epidemiology, health effects and cessation strategies.
AB  - Smokeless tobacco is an extremely addictive substance with a high rate of use in
      certain demographic groups, such as adolescents and Native Americans. In the past
      20 years, the use of smokeless tobacco has almost tripled. Health risks include
      leukoplakia (a premalignant oral lesion), oral cancer and systemic nicotine
      effects such as elevated blood pressure and serum cholesterol levels. To avoid or
      control these effects, family physicians should identify patients who use
      smokeless tobacco and encourage and support cessation efforts. Patients who are
      unsure about quitting need the risks of their habit personalized, and those who
      are actively trying to stop using smokeless tobacco need emotional and, in some
      cases, therapeutic support (e.g., nicotine replacement therapy). The family
      physician should encourage patients who appear motivated to stop using smokeless
      tobacco to set a quit date in the very near future. However, all smokeless
      tobacco users--regardless of their motivation to quit--need to be followed to
      ensure compliance with cessation advice or to detect medical complications from
      use of this form of tobacco.

PMID- 7572567
TI  - Torsades de pointes and long QT syndromes.
AB  - Torsades de pointes is a polymorphic form of ventricular tachycardia that is
      usually associated with prolongation of the QT interval. This QT prolongation may
      be either congenital or acquired. Etiologies for the acquired form include
      hypokalemia, hypomagnesemia, hypocalcemia, starvation, sick sinus syndrome,
      atrioventricular block and drug effects. Medications that have been implicated
      include most antiarrhythmic agents, some nonsedating histamine blockers,
      erythromycin and ketoconazole. Accurate and timely recognition of torsades de
      pointes is critically important because of the risk that traditional
      antiarrhythmic drug treatment will likely worsen the problem rather than improve
      it. Effective treatment requires withdrawal of any offending drugs or correction
      of the underlying cause of the QT prolongation. Beta blockers have been shown to
      be effective in preventing problems in congenitally at-risk patients. An
      implantable cardioverter defibrillator should be considered in some patients with
      recurrent episodes.

PMID- 7572568
TI  - Chlamydia trachomatis infection update.
AB  - Chlamydia trachomatis has become the most common sexually transmitted infection
      in the United States. Aggressive screening of sexually active young adults is
      needed, as well as prompt and reliable treatment of infected partners, to
      mitigate the effects of this disease. Tests using enzyme immunoassay and DNA
      probe have increased the efficiency of diagnosis through rapid detection,
      although culture remains the most reliable test. Treatment with single-dose
      azithromycin is a successful alternative to the definitive treatment, seven days
      of doxycycline therapy.

PMID- 7572569
TI  - Postpartum care.
AB  - Family physicians have a unique role in helping new mothers and their families
      manage the changes that occur during the postpartum period. Postdelivery hospital
      stays are becoming shorter, so anticipation of concerns that may arise is
      crucial. Instruction about care of the perineum and breasts, the possibility of
      postpartum depression, resumption of sexual intercourse, contraception, diet and
      exercise is appropriate in the postpartum period. The mother may also benefit
      from discussions about how to obtain practical support at home. Potential
      biomedical problems that may arise during this period include mastitis, late
      uterine hemorrhage, late endometritis, thyroiditis and incontinence. A list of
      practical questions to ask the mother can help the physician identify any issues
      or problems that need attention.

PMID- 7572571
TI  - NIH develops consensus statement on cochlear implants.

PMID- 7572570
TI  - Serotonin syndrome.
AB  - Serotonin syndrome is a potentially life-threatening complication of
      psychopharmacologic drug therapy. The syndrome is produced most often by the
      concurrent use of two or more drugs that increase brainstem serotonin activity
      and is often unrecognized because of the varied and nonspecific nature of its
      symptomatology. Serotonin syndrome is characterized by alterations in cognition,
      behavior, autonomic nervous system function and neuromuscular activity. Patients
      with serotonin syndrome usually respond to discontinuation of drug therapy and
      supportive care alone, but they may require treatment with a specific
      antiserotonergic drug such as cyproheptadine, methysergide and/or propranolol.

PMID- 7572572
TI  - American Heart Association issues statement on preventive strategies in coronary
      disease.

PMID- 7572573
TI  - Prediction of cardiac death in patients with a very low ejection fraction after
      myocardial infarction: a Cardiac Arrhythmia Suppression Trial (CAST) study.
AB  - The Cardiac Arrhythmia Suppression Trial (CAST) database was analyzed with a Cox
      proportional hazards regression model to predict the mortality of patients with
      very poor left ventricular systolic function (ejection fraction < or = .20).
      Predictors of total death or cardiac arrest were (relative risk), QRS duration
      (1.10/10 msec increase), coronary artery bypass grafting (0.38), basal heart rate
      (1.26/10 min-1 increase), diastolic blood pressure (0.79/10 mm Hg increase),
      diabetes mellitus (1.59), EF (0.94/1 U increase), and ease of suppression (the
      ability to suppress ambient ventricular ectopy on the lowest dose of the first
      randomly chosen CAST drug) (0.64). Predictors of arrhythmic death or arrhythmic
      cardiac arrest included thrombolysis (0.44), coronary artery bypass grafting
      (0.38), diuretic use (1.71), heart rate (1.21/10 min-1 increase), calcium channel
      blocker use (1.69), and QRS duration (1.10/10 msec increase). Thus easily
      measurable clinical and laboratory variables help predict prognosis in this
      clinically important subgroup. The pathophysiologic basis for and the clinical
      implications of the ease of ventricular arrhythmia suppression correlating with
      prognosis requires further study.

PMID- 7572575
TI  - Abrupt augmentation of ST segment elevation associated with successful
      reperfusion: a sign of diminished myocardial salvage.
AB  - To investigate the significance of abrupt augmentation of ST segment elevation
      immediately after reperfusion, 36 patients with an initial acute anterior
      myocardial infarction successfully treated with thrombolysis were studied.
      Immediately after reperfusion was performed, 17 (47%) patients showed abrupt
      augmentation of ST segment elevation of anterior area (E group), and 19 (53%)
      patients did not (N group). The time to reperfusion was not significantly
      different between the two groups. In the E group the peak level of creatine
      kinase MB isozyme was higher (p < 0.05) than in the N group. The left ventricular
      ejection fraction (EF) did not increase in the E group from acute to chronic
      phase. However, in the N group EF increased significantly. The difference in EF
      in the chronic phase was significant between the two groups (p < 0.05). The
      infarcted regional wall motion (RWM) did not increase in the E group, whereas in
      the N group it increased markedly (p < 0.05). In addition, the infarcted RWM in
      the chronic phase was worse in the E group than in the N group (p < 0.05). Abrupt
      augmentation of ST segment elevation associated with successful reperfusion
      appears to reflect diminished myocardial salvage.

PMID- 7572574
TI  - Concurrent nitroglycerin administration reduces the efficacy of recombinant
      tissue-type plasminogen activator in patients with acute anterior wall myocardial
      infarction.
AB  - The aim of this study was to evaluate the impact of concurrent nitroglycerin
      administration on the thrombolytic efficacy of recombinant tissue-type
      plasminogen activator (rTPA) in patients with acute anterior myocardial
      infarction (AMI). Sixty patients (53 men, 7 women; mean age 54 +/- 7 years) with
      AMI entered the study. Thirty-three patients were randomized to receive rTPA
      alone (100 mg in 3 hours) (group A) and 27 to receive rTPA plus nitroglycerin
      (100 micrograms/min) (group B). Time from the onset of chest pain and delivery of
      rTPA was similar in the two groups of patients. Patients in group A had signs of
      reperfusion more often than the patients in group B (25 of 33 or 75.7% vs 15 of
      27 or 55.5%, p < 0.05). Time to reperfusion was also shorter in group A than in
      group B (19.6 +/- 9.4 minutes vs 37.8 +/- 5.9 minutes, p < 0.05). Group B had a
      greater incidence of in-hospital adverse events (9 of 27 vs 5 of 33, p < 0.05)
      and a higher incidence of coronary artery reocclusion (8 of 15 or 53.3% vs 6 of
      25 or 24%, p < 0.05). Peak plasma levels of rTPA antigen were higher in group A
      compared with group B (1427 +/- 679 vs 512 +/- 312 ng/ml, p < 0.01). In
      conclusion, concurrent nitroglycerin administration reduces the thrombolytic
      efficacy of rTPA in patients with AMI probably by lowering the plasma levels of
      rTPA antigen. The diminished efficacy of rTPA is associated with an adverse
      outcome.

PMID- 7572576
TI  - Prognosis in acute myocardial infarction: comparison of patients with diagnostic
      and nondiagnostic electrocardiograms.
AB  - Prognosis in acute myocardial infarction has been compared in patients with and
      without diagnostic ECGs. Of 817 patients, 89.4% had ST elevation, 2.4% had left
      bundle branch block, and 8.2% had no ST elevation. Patients without ST elevation
      had a hospital mortality rate of 3.0% compared with 14.0% and 40.0%,
      respectively, in patients with ST elevation and left bundle branch block (p =
      0.0001). Event-free survival at 6 months in patients without ST elevation was
      85.6% (74.1% to 92.3%), compared with 72.9% (69.4% to 76.0%) and 31.0% (12.0% to
      52.3%) in patients with ST elevation and left bundle branch block (p < 0.001).
      The excess risk associated with ST elevation was largely attributable to the
      severity of infarction: after adjustment for Q-wave development and heart
      failure, the hazard ratio fell from 2.24 (1.43 to 4.38) to 1.76 (0.86 to 3.59).
      In conclusion, acute myocardial infarction has a considerably better prognosis
      when it is unassociated with ST elevation or left bundle branch block. This
      finding may have important implications for interventional management.

PMID- 7572577
TI  - Endogenous tissue plasminogen activator and platelet reactivity as risk factors
      for reocclusion after recanalization of chronic total coronary occlusions.
AB  - A prospective study was performed to investigate the role of the endogenous
      fibrinolytic system and platelet function for the occurrence of reocclusion after
      successful recanalization of chronic coronary occlusions. At control coronary
      angiography 8 +/- 2 weeks after recanalization, reocclusion was found in 10 (21%)
      of 47 patients. After correction for angiographic and clinical confounding
      factors, endogenous concentrations of tissue plasminogen activator (TPA) were
      lower in patients with reocclusion than in patients without. In contrast, plasma
      levels of plasminogen activator inhibitor-1 and alpha 2-antiplasmin were similar
      in the two groups. The mean platelet volume was significantly higher in patients
      with reocclusion than in patients without. In addition, agonist-induced platelet
      aggregation in platelet-rich plasma was enhanced in the patients with
      reocclusion. Decreased endogenous plasma TPA concentrations and enhanced platelet
      reactivity may contribute to the occurrence of reocclusion after primarily
      successful coronary artery recanalization.

PMID- 7572578
TI  - Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and
      lactate levels during left anterior descending coronary artery angioplasty.
AB  - This study examines acute changes in circulating levels of atrial natriuretic
      peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of
      myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age
      55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior
      descending coronary artery were studied. Angioplasty of the left anterior
      descending coronary artery was performed with the balloon inflations maintained
      at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus
      for ANP, IGF-1 (both total and free), and lactate levels at (1) after
      catheterization of the coronary sinus, (2) after the initial left coronary
      angiography, (3) immediately after balloon deflation, and (4) 5 minutes after
      deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon
      deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9).
      This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/-
      3.1; p < 0.01). ANP levels were not affected by the injections of angiographic
      contrast media. Free IGF-1 levels rose after injections of radiographic contrast
      but not after balloon inflation or deflation. Total IGF-1 levels did not change
      significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at
      the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7;
      p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither
      lactic acid levels nor release of ANP or IGF-1 correlated with the initial left
      ventricular end-diastolic pressure or the degree of electrocardiographic ST
      depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572579
TI  - Comparison of pressure-derived fractional flow reserve with poststenotic coronary
      flow velocity reserve for prediction of stress myocardial perfusion imaging
      results.
AB  - The physiologic importance of coronary stenoses can be assessed indirectly by
      stress myocardial perfusion imaging or directly by translesional pressure and
      flow measurements. The aims of this study were to compare myocardial fractional
      flow reserve (FFRmyo), a recently proposed index of lesion significance derived
      from hyperemic translesional pressure gradients, with directly measured
      poststenotic flow velocity reserve for the prediction of myocardial perfusion
      stress imaging results in corresponding vascular beds. Poststenotic coronary flow
      velocity (0.018-inch guide wire) and translesional pressure gradients (2.7F fluid
      filled catheter) were measured at baseline and after intracoronary adenosine (12
      to 18 micrograms) in 70 arteries (diameter stenosis: mean 56% +/- 15%, range 14%
      to 94% by quantitative angiography). Coronary flow reserve was calculated as the
      ratio of hyperemic to basal mean flow velocity. FFRmyo was calculated during
      maximal hyperemia as equal to 1-(hyperemic gradient [mean aortic pressure-5]),
      where 5 is the assumed central venous pressure. Positive and negative predictive
      values and predictive accuracy for reversible stress myocardial perfusion
      abnormalities were computed. There was a significant correlation between pressure
      derived FFRmyo and distal coronary flow reserve (r = 0.46; p < 0.0001). The
      strongest predictor of stress myocardial perfusion imaging results was the
      poststenotic coronary flow reserve (chi square = 33.2; p < 0.0001). The
      correlation between stress myocardial perfusion imaging and FFRmyo was also
      significant (chi square = 8.3; p < 0.005). There was no correlation between
      stress myocardial perfusion imaging and percentage diameter stenosis (chi square
      = 2.9; p = 0.10) or minimal lumen diameter (chi square = 0.47; p = 0.73). A
      poststenotic coronary flow reserve of < or = 2 had a positive predictive value of
      89% for regionally abnormal myocardial perfusion imaging abnormalities, whereas
      the positive predictive values of FFRmyo and angiographic percentage diameter
      stenosis were only 71% and 67% respectively. In conclusion, the predictive value
      of poststenotic coronary flow velocity reserve for stress-induced myocardial
      perfusion abnormalities exceeds that of the translesional FFRmyo. These findings
      should be considered when applying these techniques for clinical decision making
      in the assessment of coronary stenosis severity.

PMID- 7572580
TI  - Prognostic value of predischarge dipyridamole technetium 99m sestamibi myocardial
      tomography in medically treated patients with unstable angina.
AB  - Recently developed unstable angina clinical practice guidelines have recommended
      risk stratification with dipyridamole thallium-201 myocardial imaging in patients
      at "intermediate" pretest clinical risk who cannot exercise maximally. The
      prognostic value of predischarge dipyridamole technetium 99m sestamibi (MIBI)
      tomography has not been assessed in this clinical setting. To this end, 128
      medically treated patients with unstable angina at intermediate pretest clinical
      risk underwent follow-up for 16 +/- 11 (mean +/- SD) months after predischarge
      intravenous dipyridamole MIBI tomography. An abnormal MIBI scan result was
      present in 99 patients (77%), of whom 47 had one or more reversible and 76 had
      one or more fixed perfusion defects. Cardiac events occurred in 68 (53%) patients
      after dipyridamole testing: recurrent unstable angina (n = 36), nonfatal acute
      myocardial infarction (n = 6), or death (n = 26). A cardiac event occurred in 10%
      of patients with normal MIBI tomography results compared with 69% of those with
      abnormal results (p < 0.01). Event rates associated with specific perfusion
      defects were similar (reversible = 68%; fixed = 71%) and were greater than rates
      in patients without defects (both p < 0.05). Clinical variables associated with
      increased risk of cardiac events by univariate analysis included a history of
      congestive heart failure, prior myocardial infarction, and diabetes mellitus (all
      p < 0.05). Independent multivariable predictors (Cox proportional hazards model)
      of any cardiac event were an abnormal result of MIBI scan (relative risk [RR] =
      4.3, 95% confidence interval [CI] 1.5 to 12.0) and a reversible (RR = 1.8, 95% CI
      1.1 to 2.9) or a fixed perfusion defect (RR = 2.9, 95% CI 1.6 to 5.4).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572581
TI  - Comparison of the sensitivity and specificity of exercise electrocardiography in
      biased and unbiased populations of men and women.
AB  - To assess for sex-related differences in posttest referral bias, we compared the
      accuracy of exercise electrocardiography in biased (coronary angiography only)
      and unbiased (all unselected) populations with possible coronary disease. A
      retrospective analysis of clinical and exercise test data from 4467 patients (788
      who underwent angiography) was performed (2824 men and 1643 women). The accuracy
      of a positive exercise test result was assessed in the entire unbiased group with
      a method that used disease probability (derived with a logistic algorithm) rather
      than angiography results. We found that the sensitivity and specificity were
      significantly greater in men than in women with use of the biased or unbiased
      groups. When the results for the unbiased and biased groups were compared, the
      sensitivities for the unbiased group were significantly lower and the
      specificities were significantly higher than those of the biased group. These
      differences reflect the effects of posttest referral bias. The amounts that
      sensitivity decreased and specificity increased, however, was not different for
      men and women. Therefore, we conclude that the accuracy of exercise
      electrocardiography is lower in women than men irrespective of whether a biased
      or an unbiased group is used. However, these differences cannot be explained on
      the basis of sex-related differences in posttest referral bias.

PMID- 7572582
TI  - Effects of the new calcium antagonist mibefradil (Ro 40-5967) on exercise
      duration in patients with chronic stable angina pectoris: a multicenter, placebo
      controlled study. Ro 40-5967 International Study Group.
AB  - Mibefradil (Ro 40-5967) is a novel calcium antagonist from a new chemical class
      and is the first that selectively blocks the T-type calcium channel. In this
      multicenter, double-blind, placebo-controlled, parallel designed study, its
      antianginal and antiischemic effects were evaluated in 126 patients with chronic
      stable angina pectoris. Exercise tests were performed after 1 week of placebo
      (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once
      daily) or placebo. Highly significant dose-response relations were present across
      all treatment groups for exercise duration, time to angina, and time to ST
      segment depression. They were associated with a dose-dependent decrease in heart
      rate and blood pressure and plasma concentrations > 300 ng/ml. Mibefradil was
      well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were
      the most frequently reported adverse events; however, the first-degree
      atrioventricular block was dose-related, and only one patient discontinued the
      trial because of dizziness. The excellent efficacy and adequate safety profile of
      mibefradil may be a consequence of T-type calcium-channel selectivity.

PMID- 7572583
TI  - Vascular effects of diet-induced hypercalcemia after balloon artery injury in
      giant Flemish rabbits.
AB  - To determine whether metastatic calcification during neointima formation can
      result in neointimal calcification that simulates advanced human atherosclerosis,
      32 giant Flemish rabbits (weight 5.5 +/- 0.6 kg) underwent overstretch balloon
      injury of bilateral iliac arteries and received diet therapy for 8 weeks: high
      cholesterol (2%) and low calcium-vitamin D2 regimen (250 mg of calcium carbonate
      orally 5 times weekly and 50,000 U of calciferol intramuscularly 3 times weekly;
      group 1; n = 5); low cholesterol (0.5%) and high calcium-vitamin D2 regimen (500
      mg of calcium carbonate orally 5 times weekly and 100,000 U of calciferol
      intramuscularly three times weekly; group 2; n = 19); or 0% cholesterol and high
      calcium-vitamin D2 regimen (group 3; n = 8). The incidence of vascular
      calcification was highest (71.4%) in group 2. Eighty-one percent of calcification
      was medial. Residual strain measurements of 7 thoracic aortas from group 2
      compared to normal thoracic aortas from 8 control rabbits showed that residual
      strain was significantly increased in the calcified atherosclerotic aortas (12.3%
      vs 5.2%; p = 0.001). We conclude that diet-induced hypercalcemia predominantly
      affects the media despite the presence of concomitant neointima formation from
      balloon artery injury with or without hypercholesterolemia and increases the
      residual strain more than twofold compared to normal thoracic aortas.

PMID- 7572584
TI  - Intravascular ultrasound approach to the diagnosis of coronary artery aneurysms.
AB  - Coronary artery aneurysms are usually diagnosed by contrast coronary angiography,
      which portrays the silhouette of the lumen but cannot distinguish true and false
      aneurysms. To differentiate true and false aneurysms and to study the morphologic
      changes of the vessel wall, intravascular ultrasound (IVUS) was performed in
      patients with angiographic signs of coronary artery aneurysms. We used a 4.8F or
      3.5F, 20 MHz IVUS catheter for ultrasound examination. Fourteen patients (12 men
      and two women ranging in age from 43 to 73 years) with angiographic signs of
      coronary aneurysm were enrolled. IVUS imaging was optimally obtained in all
      patients. The vessel area, lumen area, and plaque area of the aneurysm segment
      and of the proximal and distal segments were determined. IVUS showed that both
      the proximal and distal reference segments were severely affected by
      atherosclerotic lesions in all the patients and by calcium deposits in six
      patients. The percent stenoses were 63.0% +/- 13.7% and 60.9% +/- 17.8% in the
      proximal and distal reference segments, respectively. In nine patients the walls
      of the aneurysms showed signs of atherosclerosis. Three angiographically
      indicated aneurysms were found to be plaque ruptures. Although the lumen and the
      vessel areas of the aneurysm segments were larger than those of the proximal and
      distal segments (p < 0.01 and (p < 0.001), no significant differences in plaque
      area and plaque composition were found between the aneurysm segment and adjacent
      vessel segments (p > 0.05). In conclusion, IVUS allows detailed characterization
      of coronary aneurysms. Atherosclerosis seems to play an important role in the
      formation of acquired coronary aneurysms.

PMID- 7572586
TI  - Comparison of early and late complications in patients undergoing coronary artery
      bypass graft surgery with and without concomitant placement of an implantable
      cardioverter defibrillator.
AB  - Previous studies have reported a significant morbidity and mortality associated
      with coronary artery bypass graft (CABG) surgery in conjunction with the
      placement of an implantable cardioverter defibrillator (ICD) with an epicardial
      lead system. In the absence of a control group, how significantly the component
      of concomitant placement of the ICD system contributes to these untoward outcomes
      remains unknown. The purpose of this study was to assess the short- and long-term
      complications in patients undergoing CABG surgery in conjunction with the
      placement of an ICD with epicardial leads and to compare these complications with
      those of patients who had only CABG surgery (control group). The study group
      (group A) consisted of 56 patients who underwent CABG surgery and placement of an
      ICD pulse generator with epicardial leads. A control group (group B) consisted of
      56 patients who underwent CABG surgery only during the same time period. The two
      groups were matched for age, sex distribution, left ventricular function,
      surgical approach, number of bypass grafts per patient, bypass pump time, and
      length of follow-up period. The early mortality for group A was 7.1% versus 1.8%
      for group B (p > 0.05). The incidence of early morbidity (congestive heart
      failure, infection, supraventricular and ventricular arrhythmias) for groups A
      and B was similar (26.8% vs 25.0%, p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572585
TI  - Heart rate variability depression in patients with unstable angina.
AB  - The degree of reduction in heart rate variability (HRV) after myocardial
      infarction has been shown to have prognostic significance, but HRV has not been
      studied extensively in patients with unstable angina. We assessed spectral and
      nonspectral measurements of HRV in 52 patients with unstable angina, 52 patients
      with acute myocardial infarction, and 41 normal subjects. The spectral bands of
      0.04 to 0.15 Hz (low frequency), 0.15 to 0.4 (high frequency), and nonspectral
      parameters SDNN, SDANN, SDNN index, rMSSD, and pNN50 were calculated from
      continuous 24-hour ECGs. All measures of HRV were reduced in patients with acute
      coronary syndromes compared to normal controls (p < 0.001), and there was no
      significant difference in measure of HRV between unstable angina and myocardial
      infarction patients. In patients with unstable angina who stabilized after
      admission, HRV had increased by the second 24 hours of monitoring. In contrast,
      HRV was further depressed in patients who had episodes of chest pain or transient
      ST-segment depression during the second 24 hours. rMSSD, pNN50, and SDNN index
      were lower in patients with unstable angina who had transient silent ischemia
      compared to those without silent ischemia. Of the patients with unstable angina,
      4 died and 1 had nonfatal acute myocardial infarction within 11 months. HRV was
      lower in these patients than in patients without further cardiac events.

PMID- 7572587
TI  - Efficacy of pindolol for treatment of vasovagal syncope.
AB  - The purpose of this study was to evaluate the efficacy, safety, and tolerance of
      pindolol as initial therapy for vasovagal syncope. Head-up tilt table testing
      (HUT) was performed on 192 patients for syncope or near-syncope of unknown cause.
      Forty-four (23%) patients had a positive HUT for vasovagal syncope, and 28 (64%)
      received oral pindolol as initial therapy. Three patients were lost to follow-up;
      of the remaining 25 patients (mean age 60 +/- 22 years), 15 were women, 14 had
      syncope, and 11 had near-syncope. At 14 +/- 6 months' follow-up, 16 (64%)
      patients were without recurrence or side effects from pindolol. Of the 9 patients
      who stopped taking pindolol, 3 were switched to another regimen for recurrent
      symptoms, 2 stopped because of side effects, and 4 did not comply with the
      regimen. In conclusion, pindolol appears to be safe and effective as initial
      treatment for vasovagal syncope.

PMID- 7572588
TI  - Sotalol for refractory arrhythmias in pediatric and young adult patients: initial
      efficacy and long-term outcome.
AB  - Sotalol is an antiarrhythmic medication that has properties of both a beta
      blocker and a class III agent and has been used safely and effectively to treat
      arrhythmias of multiple mechanisms in pediatric patients. The purpose of this
      study was to review our institutional experience with sotalol in 45 patients with
      refractory arrhythmias and determine their long-term outcome. Patients responded
      to sotalol with 80% efficacy and a 22% incidence of adverse side effects. The
      mean sotalol dose was 116 mg/m2/day, and the average duration of therapy was 15.2
      months. In spite of 80% efficacy, only 22% of patients remained on sotalol long
      term. Sotalol was discontinued most commonly for either spontaneous resolution of
      disease or definitive cure by radiofrequency ablation. Other reasons for
      discontinuation of effective therapy included adverse side effects and arrhythmia
      control with either an antitachycardia pacemaker or another medication. One
      patient died while taking sotalol, but this case was considered a failure of
      treatment rather than an adverse side effect. Of the patients who still receive
      therapy, several have complex structural heart disease and require a combination
      of therapies, including sotalol, for adequate rhythm control.

PMID- 7572589
TI  - Escalating nitrate dose overcomes early attenuation of hemodynamic effect caused
      by nitrate tolerance in patients with heart failure.
AB  - This study was performed to examine the hypothesis that an early attenuation of
      nitrate effect caused by nitrate tolerance can be overcome by dose increase. We
      compared hemodynamic effects of constant dose (40 to 120 mg) of oral isosorbide
      dinitrate (ISDN) given every 6 hours for three doses followed by 12 hours of
      nitrate washout interval with those of escalating dose (40 mg, 80 mg, and 120 mg)
      in two similar groups of patients with chronic congestive heart failure.
      Escalating ISDN dose resulted in a progressive increase in ISDN blood level and
      overcame early attenuation of effect occurring with a constant dose. At peak
      effect of the third ISDN dose, a significantly greater reduction was seen in mean
      right atrial pressure (-59% +/- 27% vs -20% +/- 22%, p < 0.01), mean pulmonary
      artery pressure (-29% +/- 11% vs -11% +/- 15%, p < 0.01) and mean pulmonary
      artery wedge pressure (-39% +/- 19% vs -19% +/- 23%, p < 0.05) with the
      escalating dose. These findings demonstrate that early attenuation of hemodynamic
      effect caused by nitrate tolerance can be overcome by dose escalation.

PMID- 7572590
TI  - Echocardiographic characterization of left ventricular adaptation in a
      genetically determined heart failure rat model.
AB  - This study uses echocardiography to characterize the pattern of left ventricular
      hypertrophy in a new hypertensive heart failure-prone rat strain designated
      SHHF/Mcc-cp (SHHF). M-mode echocardiograms of the left ventricle in nine 10- to
      12-month old SHHF rats and nine age-matched spontaneously hypertensive rats (SHR)
      were compared. Wistar-Kyoto and Sprague-Dawley strains served as the normotensive
      control group. SHHF rats had significantly greater left ventricular mass than did
      rats in the normotensive control group. Although left ventricular mass was not
      different between SHHF and SHR, significant differences were seen in the pattern
      of left ventricular remodeling as determined by relative wall thickness. These
      differences in left ventricular remodeling may explain the earlier development of
      heart failure in SHHF. The different patterns of left ventricular hypertrophy in
      SHHF and SHR suggests that heart failure in SHHF is not mediated by hypertension
      alone.

PMID- 7572591
TI  - Three-dimensional echocardiography improves noninvasive assessment of left
      ventricular volume and performance.
AB  - To calculate left ventricular (LV) volume by two-dimensional echocardiography
      (2DE), assumptions must be made about ventricular symmetry and geometry. Three
      dimensional echocardiography (3DE) can quantitate LV volume without these
      limitations, yet its incremental value over 2DE is unknown. The purpose of this
      study was to compare the accuracy of LV volume determination by 3DE to standard
      2DE methods. To compare the accuracy of 3DE with standard 2DE algorithms for
      quantitating LV volume, 28 excised canine ventricles of known volume and varying
      shapes (15 symmetric and 13 aneurysmal) and 10 instrumented dogs prepared so that
      instantaneous ventricular volume could be measured were examined by 2DE (bullet
      and biplane Simpson's formulas) and again by 3DE. In both excised and beating
      hearts, 3DE was more accurate in quantitating volume than either 2DE method
      (excised: error = 0.6 +/- 3.2, 2.5 +/- 10.7, and 4.0 +/- 8.5 ml by 3D, bullet,
      and Simpson's, respectively; beating: error = -0.5 +/- 3.5, -0.3 +/- 9.6, and 
      7.6 +/- 8.0 ml by 3DE, bullet, and Simpson's, respectively). This difference in
      accuracy between 3DE and 2DE methods was especially apparent in asymmetric
      ventricles distorted by ischemia or right ventricular volume overload. Stroke
      volume and ejection fraction calculated by 3DE also demonstrated better agreement
      with actual values than the bullet or Simpson methods with less variability
      (ejection fraction: error = -2.0% +/- 5.1%, 7.7% +/- 8.5%, and 6.8% +/- 12.3% by
      3DE, bullet, and Simpson's, respectively). In both in vitro and in vivo settings,
      3DE provides improved accuracy for LV volume and performance than current 2DE
      algorithms.

PMID- 7572592
TI  - Myocardial atrophy in acquired immunodeficiency syndrome--associated wasting.
AB  - This study evaluated the effects of acquired immunodeficiency syndrome wasting
      syndrome (AWS) on the heart in a population free of overt opportunistic infection
      or clinical evidence of cardiac disease. Data from 53 patients with AWS and 16
      healthy age-matched controls were studied. By echocardiography, a significant
      reduction in left ventricular mass was found in patients with AWS that remained
      significantly reduced when corrected for body surface area. Mean ejection
      fraction was within the normal range in patients with AWS but was significantly
      less than in controls. End-systolic volume index was slightly elevated in
      patients with AWS. Although no difference in end-systolic wall stress was seen,
      the end-systolic wall stress-shortening relation differed significantly. These
      findings are consistent with myocardial atrophy and subtle left ventricular
      dysfunction in patients with AWS.

PMID- 7572593
TI  - Quantification of right ventricular function with magnetic resonance imaging in
      children with normal hearts and with congenital heart disease.
AB  - In clinical treatment of children with congenital heart disease (CHD) assessment
      of right ventricular (RV) function is important. Available imaging techniques
      have been of limited value because of technical factors and the complex geometry
      of the right ventricle. To validate magnetic resonance (MR) imaging measurements
      of RV function in children, gradient echo MR imaging of both ventricles and MR
      flow mapping of great vessel and tricuspid flow was performed in 20 children with
      CHD affecting the right ventricle and in 22 healthy children ranging in age from
      5 to 16 years. Close correlation between RV versus LV stroke volumes (r = 0.96)
      and RV stroke volume versus great artery (r = 0.97) or tricuspid flow (r = 0.97)
      was observed with small interobserver and intraobserver variability. Results of
      healthy children were end-diastolic volume: 70 +/- 9 ml/m2, end-systolic volume:
      21 +/- 5 ml/m2, and ejection fraction: 70% +/- 4%. In the patient groups
      clinically important differences were noted. We conclude that MR imaging provides
      accurate noninvasive measurements of RV function in healthy children and patients
      with (operated) CHD.

PMID- 7572594
TI  - Effects of blood donation on exercise performance in competitive cyclists.
AB  - This study evaluated 10 male cyclists before and after phlebotomy to determine
      the effect of donation of 1 U of blood on exercise performance. Each subject
      underwent maximal exercise testing with oxygen consumption measurement at
      baseline, 2 hours after phlebotomy, 2 days after phlebotomy, and 7 days after
      phlebotomy. Maximal performance was decreased for at least 1 week. Submaximal
      performance was unaffected by blood donation.

PMID- 7572595
TI  - Three-period crossover trial with ambulatory blood pressure monitoring for
      evaluating antihypertensive therapy.
AB  - A double-blind, three-period, crossover trial used 24-hour ambulatory blood
      pressure monitoring to compare diltiazem controlled diffusion (CD) 300 mg with
      placebo. Patients with hypertension (N = 43) were randomly assigned to one of
      four crossover treatment sequences of three treatment periods each. Ambulatory
      blood pressure was obtained at the end of each 4-week treatment period. Diltiazem
      CD significantly decreased diastolic and systolic blood pressure at bihourly
      ambulatory blood pressure evaluations (p < 0.05, all). However, when all
      ambulatory blood pressure monitoring data were combined into one statistical
      model, blood pressure reductions were quantifiably similar to those in the
      overall bihourly analysis, but with a consistent 24-hour antihypertensive effect
      for both diastolic and systolic blood pressure relative to that with placebo
      (i.e., parallel blood pressure profiles) and with increased precision. Mean +/-
      SE changes in diastolic and systolic blood pressure across the 24-hour dosing
      interval were -5.6 +/- 0.4 mm Hg and -7.6 +/- 0.5 mm Hg, respectively (p < 0.001,
      both). Therefore, by using a crossover design with ambulatory blood pressure
      monitoring, we showed diltiazem CD to reduce blood pressure consistently
      throughout a 24-hour dosing interval in comparison with placebo in patients with
      hypertension.

PMID- 7572596
TI  - Major determinants of survival and nonsurvival of intraaortic balloon pumping.
AB  - The purpose of this study was to find the major determinants of survival and
      nonsurvival after intraaortic balloon pump (IABP) support. One hundred twenty
      nine consecutive patients with IABP support from January 1988 to January 1992
      were analyzed retrospectively. Differences between the survival and nonsurvival
      groups were tested with the Student's t test, chi-squared test, and frequency
      analysis. The overall survival rate was 50.4% (65 of 129). Nonsurvivors (64 of
      129, 49.6%) had higher rates of chronic heart failure (21.9% vs 9.2%, p < 0.05),
      acute myocardial infarction (53.1% vs 24.6%, p < 0.01), cardiomyopathy (9.4% vs
      1.5%, p < 0.05), New York Heart Association functional class IV (51.6% vs 13.9%,
      p < 0.01), and depressed left ventricular ejection fraction (29.38% +/- 8.99% vs
      42.88% +/- 5.24%, mean +/- SD, p < 0.01). The nonsurvival group also had longer
      duration of cardiopulmonary bypass (115.80 +/- 24.43 vs 78.34 +/- 3.81 min, mean
      +/- SEM, p < 0.02) and aortic occlusion (57.55 +/- 13.03 vs 41.00 +/- 2.79 min,
      mean +/- SEM, p < 0.05) than the survival group. The major determinants of death
      after IABP are acute myocardial infarction, left ventricular ejection fraction <
      30%, New York Heart Association functional class IV, and longer duration of
      cardiopulmonary bypass and aortic occlusion. IABP is effective in sustaining
      hemodynamics, but severe myocardial pump failure portends a poor treatment
      outcome.

PMID- 7572597
TI  - Angioscopic detection of residual pulmonary thrombi in the differential diagnosis
      of pulmonary embolism.
AB  - Definite diagnosis of pulmonary embolism (PE) by conventional methods such as
      angiography is frequently difficult. If residual thromboemboli incorporated into
      the pulmonary arterial wall or in the distal small segments are visible,
      differential diagnosis of PE versus primary pulmonary hypertension (PPH) can be
      made without open-chest pulmonary biopsy. Six patients suspected of having acute
      PE, 6 suspected of having chronic PE, and 4 with PPH diagnosed by pulmonary
      biopsy underwent percutaneous pulmonary angioscopy. In patients suspected of
      having PE, globular and mural thromboemboli were detected by both angioscopy and
      angiography in 4 and 1 patients, respectively. By angioscopy, emboli incorporated
      into the arterial wall were detected in 7 and microemboli obstructing the distal
      small segments were detected in 6. However, these emboli were detected by
      angiography in none. In patients with PPH, no embolus was detected by angioscopy
      and angiography. Angioscopically, however, stenoses were observed in the distal
      small segments in all patients. The results indicate that residual pulmonary
      thromboemboli in PE and stenoses of distal pulmonary arteries in PPH are
      detectable by percutaneous angioscopy, and therefore this method is feasible for
      differential diagnosis of PE.

PMID- 7572599
TI  - Treatment of arrhythmias during pregnancy.
AB  - The treatment of arrhythmias during pregnancy is complicated by concerns for
      fetal well-being. Although no drug is absolutely safe, most are well tolerated.
      Nonpharmacologic therapy includes vagal maneuvers and esophageal pacing.
      Temporary and permanent pacing have been used safely during pregnancy, as has
      direct current cardioversion. Cardiopulmonary resuscitation is complicated by
      concerns for the fetus, which may be viable at 25 weeks. Diagnosis of the cause
      of tachyarrhythmias may be enhanced by roving chest leads or esophageal
      recording. Both supraventricular and ventricular tachycardias may become manifest
      during pregnancy, and conservative management is desirable if the symptoms are
      mild. Supraventricular tachycardias respond acutely to adenosine. Ventricular
      arrhythmias during pregnancy often occur in the absence of structural heart
      disease and are responsive to drug therapy. The safe use of an implantable
      cardioverter-defibrillator has been described.

PMID- 7572598
TI  - Peripartum cardiomyopathy.
AB  - Congestive heart failure is an uncommon complication of pregnancy with
      potentially life-threatening consequences. Peripartum cardiomyopathy is a disease
      of unknown cause in which severe left ventricular dysfunction occurs during late
      pregnancy or the early puerperium. In the past, the diagnosis of this entity was
      made on clinical grounds; however, modern echocardiographic techniques have
      allowed more accurate diagnoses by excluding cases of diseases that mimic the
      clinical symptoms and signs of heart failure. Risk factors for peripartum
      cardiomyopathy include advanced maternal age, multiparity, African descent,
      twinning, and long-term tocolysis. An extensive search for the causes of
      peripartum cardiomyopathy has been unrevealing. Treatment includes digitalis,
      diuretic agents, and vasodilators. Anticoagulation is strongly recommended,
      especially if ventricular function is persistent. The prognosis of peripartum
      cardiomyopathy is related to the recovery of ventricular function. Caution is
      advised in recommending subsequent pregnancy, especially if left ventricular
      dysfunction is persistent.

PMID- 7572601
TI  - Semiquantitation of regional myocardial blood flow in normal human subjects by
      first-pass magnetic resonance imaging.
AB  - The purpose of this study was to investigate the feasibility of first-pass MR
      imaging for measurement of regional myocardial blood flow in human beings. The
      first pass of the contrast agent Gd-DTPA through the myocardium was imaged in 12
      normal volunteers with an ECG-gated Turbo-Flash sequence. The MTT of the contrast
      agent through the myocardium after a bolus injection was derived from curves of
      SI versus time. The bolus was injected through an intravenous catheter, which was
      advanced to the central venous position (preferably the right atrium). To
      investigate myocardial input function, different bolus concentrations and
      catheter positions were compared. It is concluded that first-pass MR imaging is
      feasible in human subjects when a central injection of 0.03 mmol/kg of Gd-DTPA is
      applied. MTT values were similar throughout the myocardium of normal subjects at
      rest, reflecting normal perfusion. Absolute values of MTT were related to the
      myocardial input.

PMID- 7572600
TI  - Novel antiplatelet therapies for treatment of patients with ischemic heart
      disease: inhibitors of the platelet glycoprotein IIb/IIIa integrin receptor.
AB  - Blood platelets play essential roles in normal coagulation and in coronary
      atherosclerotic disease and its complications. Various antiplatelet therapies,
      including aspirin, ticlopidine, and dipyridamole, have been developed for use in
      patients with known coronary artery artery disease to prevent ischemic
      complications. More recently a more complete anti-aggregation effect has been
      accomplished by the use of monoclonal antibodies and specific peptide and
      nonpeptide compounds that bind to the platelet GP IIb/IIIa surface receptor. This
      receptor becomes activated by platelet stimulation and binds fibrinogen molecules
      between platelets in the aggregation process. These new antiplatelet drugs are
      now being evaluated in clinical trials in patients undergoing balloon coronary
      angioplasty, in whom fewer ischemic events occur when the receptor blocker is
      used intravenously than with standard therapy, and in patients with stable and
      unstable angina. Excessive bleeding is an important problem with these agents,
      and efforts must be made to eliminate this side effect.

PMID- 7572603
TI  - Thrombolysis of right atrial thrombus with pulmonary embolism in anticardiolipin
      antibody syndrome.

PMID- 7572602
TI  - Aortic regurgitation progressing to aortic stenosis in antiphospholipid syndrome.

PMID- 7572604
TI  - Right coronary artery to right atrium fistula mimicking a right atrial mass.

PMID- 7572605
TI  - Pheochromocytoma with reversible focal cardiac dysfunction.

PMID- 7572607
TI  - Aborted sudden death in dual-chamber pacemaker treatment of hypertrophic
      obstructive cardiomyopathy.

PMID- 7572606
TI  - Glycogen storage disease type III associated with ventricular tachycardia.

PMID- 7572609
TI  - Usefulness of QTc dispersion in interpreting exercise electrocardiograms.

PMID- 7572608
TI  - Shortening of the QT interval immediately preceding the onset of idiopathic
      spontaneous ventricular tachycardia.

PMID- 7572610
TI  - Incomplete, delayed functional recovery late after reperfusion following acute
      myocardial infarction: "maimed myocardium".
AB  - The objective of the current editorial is to introduce a new concept ("maimed
      myocardium") that we believe describes more accurately the incomplete, delayed
      recovery of LV function that may occur late after reperfusion after AMI. It has
      been demonstrated previously that myocardium remains viable for a prolonged
      period in many patients with nonsustained coronary occlusion, despite the
      occurrence of myocardial necrosis; late reperfusion may result in myocardial
      salvage in reversibly ischemic (stunned) segments (complete recovery) and in
      intensely injured (maimed) segments that display partial return of LV function
      over time (incomplete recovery). Clinically, the basis for maimed myocardium is
      the observation that delayed, LV functional recovery may occur in partially
      infarcted segments where there has been an antecedent ischemic insult of
      sufficient duration to result in some degree of myocardial necrosis. Certain
      acute coronary syndromes characterized by nonsustained coronary occlusion
      followed by spontaneous reperfusion (e.g., non-Q-wave AMI) or drug-induced
      reperfusion induced by the exogenous administration of thrombolytic therapy are
      associated with incomplete, delayed recovery of LV function as detected
      clinically by partial improvement in serial radionuclide-ejection measurement,
      enhanced metabolic integrity of cardiac tissue by F-18 deoxyglucose myocardial
      imaging, and scintigraphic findings of reverse thallium redistribution--findings
      that support the presence of partially viable myocardium that has been
      incompletely salvaged during reperfusion late after AMI. Experimentally, delayed
      LV functional recovery has been reported in animal models in which prolonged
      coronary occlusion (hours to days) followed by reperfusion is associated with
      late recovery of regional LV function in myocardial segments subtending border
      (stunned) zones and central infarct (maimed) zones. In studies in animals and
      human beings, postextrasystolic potentiation and pharmacologic inotropic
      interventions may augment maimed and stunned segments, although the magnitude of
      regional contractile reserve that can be unmasked with these interventions is
      quantitatively less in the maimed than in stunned segments. In summary, the
      propensity of intensely injured or partially infarcted LV segments to display
      intermediate functional recovery followed by reperfusion late after coronary
      occlusion suggests that even severely depressed but residually viable cardiac
      muscle can be salvaged incompletely over time.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7572611
TI  - Control of paint overspray in autobody repair shops.
AB  - Commercially available controls for reducing worker exposure to paint overspray
      were evaluated in six autobody shops and a spray-painting equipment
      manufacturer's test facility. Engineering control measures included spray
      painting booths, vehicle preparation stations, and spray-painting guns. The
      controls were evaluated by measuring particulate overspray concentrations in the
      worker's breathing zone, visualizing the airflow in spray-painting booths and
      vehicle preparation stations, and measuring airflow volumes and velocities. In
      addition, respirator usage observations were collected at five of the autobody
      repair shops, and quantitative fit tests were conducted on existing respirators
      at three shops. Several conclusions were drawn from this study. Downdraft spray
      painting booths provide lower particulate overspray concentrations measured on
      the worker than crossdraft and semidowndraft spray-painting booths. In the latter
      two booths, the spray-painting gun can disperse as much as half the paint
      overspray into the incoming fresh air, increasing worker overspray exposure.
      Vehicle preparation stations have no walls to contain the overspray and,
      commonly, a single exhaust fan removes air from the painting area. Airflow
      patterns suggest that these do not control the paint overspray. Switching from a
      conventional spray-painting gun to a high-volume low pressure spray-painting gun
      reduced the particulate overspray concentration by a factor of 2 at a
      manufacturer's test facility. However, this change did not significantly affect
      solvent concentrations. Finally, respirator usage in five of the six shops
      studied was inappropriate. Respirators were poorly maintained and/or did not fit
      the workers, perhaps due to the absence of a formal respirator program.

PMID- 7572613
TI  - Sample size formulae for estimating the true arithmetic and geometric mean of
      lognormal exposure distributions.

PMID- 7572612
TI  - ELPAT program report: background and current status (July 1995). Environmental
      Lead Proficiency Analytical Testing.

PMID- 7572614
TI  - Silicon carbide whiskers: characterization and aerodynamic behaviors.
AB  - Silicon carbide (SiC) whiskers are fiberlike materials with a wide range of
      industrial applications. Industrial hygiene samplings of the material are taken
      to monitor and control possible exposures to workers. This study characterizes an
      SiC whisker in detail, including its width-length distribution, aspect ratio,
      particle density, and aerodynamic size distribution. The SiC whiskers were
      aerosolized, and samples from a filter, cascade impactor, and aerosol centrifuge
      were taken. The diameter-length distribution of SiC fibers determined by electron
      microscopy from filter samples was found to follow the bivariate lognormal
      distribution. The aerodynamic size of a fiber aerosol depends not only on the
      particle dimension and density but also on the orientation of its axis with
      respect to flow. The results show that the aerodynamic size distribution obtained
      from the impactor was consistent with the predicted value, assuming the long axis
      of the fiber was parallel to the flow toward the collection substrate. On the
      other hand, the aerodynamic size in the aerosol centrifuge was consistent with
      results for a perpendicular orientation. A larger aerodynamic size (20-25%) was
      obtained in the case of impactor data as compared with centrifuge data. The
      respirable fraction estimated from the cascade impactor data was 65%, consistent
      with the estimate from bivariate analysis (67%) but smaller than the estimated
      fraction from the aerosol centrifuge (76%). The results show that the data
      obtained with the bivariate analysis of fiber dimensions had good correlation
      with the cascade impactor data, and this approach can be used to predict the
      aerodynamic size distribution and the size-selective fractions for fiber aerosols
      from filter samples.

PMID- 7572616
TI  - Exposure while applying industrial antimicrobial pesticides.
AB  - Forty-three assessments were made of dermal and/or inhalation chemical exposure
      while applying industrial antimicrobial pesticide products, either by manually
      pouring or pumping liquids or by pouring a solid (powder or flake) product.
      Inhalation exposure was assessed via a personal air sample but was usually below
      the chemical limit of detection. Dermal exposure outside work clothing and dermal
      deposition inside the clothing was assessed via dermal gauze dosimeters. While
      dosimeters at discrete body locations often received exposures below the limit of
      detection, one or more dosimeters on individual applicators almost always showed
      measurable exposure. The median measured dose was between 30% and 70% of the
      maximum credible summed dose calculated by assuming that each dosimeter showed
      either the level of measurable deposition or one-half of the detection limit at
      locations where the chemical was unmeasurable. Because of differences in settings
      and the low level of control implicit in these application processes, measurable
      dermal doses were highly variable. Mean measurable dose rates were near 3, 8, and
      10 mg product/hr, and daily total deposited doses were 2, 3.5, and 5 mg of
      product for pouring and pumping liquids and for pouring solids, respectively.
      Although the effect of gloves cannot be directly determined, wearers of gloves
      had geometric mean hand total doses 155- to 290-fold less than those not wearing
      gloves. Similar to the statistics for agricultural pesticides, the dermal route
      of exposure for these industrial pesticides exceeds the inhalation route by 5X to
      100X, depending on assumptions regarding nondetectable values.

PMID- 7572615
TI  - Factors affecting microbiological colony count accuracy for bioaerosol sampling
      and analysis.
AB  - The effects of the following variables on the occurrence of colony masking (the
      indistinguishable merging or overlap of sufficiently close colonies) were
      evaluated experimentally using the bacterium Bacillus subtilis: spore density on
      a collection surface, concentration of nutrients in the culture medium, sample
      incubation time, and ability of an observation system to distinguish overlapped
      colonies. Increasing spore surface density and incubation time increased colony
      masking, whereas lowering nutrient concentration decreased colony diameter and,
      therefore, masking but also limited spore germination and growth. Overall, full
      strength medium was best for accurate counting of early microcolonies examined
      with the aid of a microscope, whereas half- or quarter-strength medium was better
      for counting older readily observable macrocolonies. Masking bias was determined
      for varying spore surface densities and colony diameters and was applied to two
      widely used slit-to-agar bioaerosol impactors. Appropriate collection times have
      been determined for these samplers to minimize colony masking for expected
      bioaerosol concentrations. It was found, for example, that 6-min samples
      collected from an environment with an air concentration of 10(3) CFU m-3 would
      result in colony surface densities, for 3-mm colonies, of 1.5 and 3.9
      microorganisms cm-2 for the two samplers with respective masking biases of < 10%
      and < 20%.

PMID- 7572618
TI  - Fuzzy cluster analysis of positive stress tests, a new method of combining
      exercise test variables to predict extent of coronary artery disease.
AB  - Fuzzy set theory is useful in the analysis of data having a graded degree of
      abnormality. Previous studies using sharp cutoff points between normality and
      abnormality have resulted in general guidelines for the interpretation of
      positive stress tests, but do not enable the clinician to simultaneously combine
      several stress test variables, each having a range of abnormality. In this study,
      positive stress test results from 109 patients were reviewed. An angiogram
      recorded within 1 month of the stress tests showed that 100 patients had coronary
      artery disease (CAD) (15 had left main CAD, and 27 had 3-vessel, 30 had 2-vessel,
      and 28 had 1-vessel disease) and 9 were normal. Six variables were selected for
      fuzzy cluster analysis: ST-segment change, difference between resting systolic
      and peak exercise systolic blood pressure, total treadmill time, peak exercise
      heart rate as a percentage of 100% predicted maximum for age, time to onset of
      angina, and duration of repolarization abnormalities. The analysis used a
      similarity measure to compute how closely each stress test resembled a
      prototypical mildly, moderately, or severely abnormal stress test. Stress tests
      classified by this method showed better correlation with the extent of CAD than
      the degree of ST-segment depression alone. Unlike tests with mild degrees of ST
      depression (0.5 to 1.5 mm), tests classified as mild by the method virtually
      excluded high-grade CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572617
TI  - Efficacy of high-intensity exercise training on left ventricular ejection
      fraction in men with coronary artery disease (the Training Level Comparison
      Study).
AB  - The purpose of this study was to compare high- versus low-intensity exercise
      training on the change in echocardiographic left ventricular ejection fraction
      (LVEF) from rest to peak exercise. Sedentary men with coronary artery disease,
      aged 30 to 70 years, were randomized to dynamic exercise training of either low
      intensity, 50% of maximal oxygen consumption, n = 89; or high intensity, 85% of
      maximal oxygen consumption, n = 111. No other interventions were imposed and
      patients were evaluated at 6 months and 1 year. Both exercise groups
      significantly increased exercise capacity without adverse events, but the
      increase was greater (p = 0.02) in the high-intensity exercise group. The mean
      exercise test rest-peak LVEF in the high-intensity group rose from 6.20% at
      baseline to 6.54% in 6 months and to 6.73% at 12 months, while the low-intensity
      group showed no improvement at 6 months and a decrease at 12 months. Multivariate
      analyses revealed that treatment group (high versus low intensity) significantly
      contributed to the change in rest-peak LVEF. When the exercise groups were
      subdivided by initial baseline LVEF < or = 50% versus > 50%, those with the
      higher LVEF in the high-intensity group showed a greater (p = 0.05) increase in
      the rest-peak LVEF from baseline to 1 year. Over a 1-year period, exercise
      capacity improved in both exercise-intensity groups, but more so in the high
      intensity group, with no adverse events. The high-intensity group, compared with
      the low-intensity, showed more improvement in the rest-peak LVEF, especially in
      those with a higher LVEF at baseline.

PMID- 7572619
TI  - Dobutamine stress echocardiography predicts early wall motion improvement after
      elective percutaneous transluminal coronary angioplasty.
AB  - In 24 patients with chronic coronary artery disease, dobutamine stress
      echocardiography (DSE) was performed within 2 days before and after successful
      elective percutaneous transluminal coronary angioplasty (PTCA) in a blinded
      fashion. Patients with ischemic response on DSE before PTCA had significant
      improvement in the global peak-dose DSE score index after PTCA (1.62 +/- 0.35 to
      1.40 +/- 0.29, p < 0.001), whereas patients without ischemic response had no
      improvement. The positive and negative predictive values of pre-PTCA DSE on early
      myocardial ischemia relief after angioplasty were 93% and 80%, respectively. In
      patients showing contractility recruitment during low-dose dobutamine infusion in
      the DSE before PTCA, there was significant improvement in the global resting wall
      motion score index in the DSE after PTCA (1.48 +/- 0.43 to 1.34 +/- 0.33, p =
      0.004), while patients without contractility recruitment showed no improvement.
      Again, the positive and negative predictive values of pre-PTCA DSE on early
      hibernation recovery following angioplasty were 80% and 89%, respectively. In
      conclusion, DSE in patients with chronic, stable coronary artery disease
      accurately predicts wall motion improvement after successful angioplasty, and the
      expected improvement is safely demonstrated early after the procedure.

PMID- 7572620
TI  - Increased heart rate response to laboratory-induced mental stress predicts
      frequency and duration of daily life ambulatory myocardial ischemia in patients
      with coronary artery disease.
AB  - This study assessed the relation between hemodynamic data during a standardized
      mental stressor and ambulatory ischemia to determine if laboratory-induced
      responses could predict the magnitude of daily life ischemia. Forty-two men and
      11 women, aged 46 to 79 years (mean 61), with coronary artery disease and
      exercise-induced ischemia were studied. All patients underwent 24- to 48-hour
      ambulatory electrocardiographic (ECG) monitoring (mean 43 +/- 0.8 hours) and
      laboratory-induced mental stress using a public speaking task. Hemodynamic data
      were obtained at rest and every minute during mental stress. Thirty-three of 53
      patients (62%) had at least 1 ischemic episode during ECG monitoring. In patients
      who had ambulatory ischemia, there was a mean number of 7.9 +/- 1.8 episodes
      (mean total duration 79.2 +/- 24.1 minutes/48 hours). Significant positive
      correlations were found for peak heart rate and changes in heart rate during
      mental stress and ambulatory ischemia (r = 0.353 to 0.462, p < 0.05) in patients
      who had ambulatory ischemia. There was no correlation between systolic blood
      pressure during mental stress and ambulatory ischemia. Results of this study
      demonstrate that heart rate response during laboratory-induced mental stress
      correlates with magnitude of ischemia on ambulatory ECG monitoring in patients
      with coronary artery disease.

PMID- 7572621
TI  - Comparison of intravascular ultrasonic findings after coronary balloon
      angioplasty evaluated in vitro with histology.
AB  - This study investigated whether vascular damage and quantitative changes observed
      with intravascular ultrasound at the most stenotic site are representative of the
      ultimate outcome after coronary balloon angioplasty. Atherosclerotic coronary
      arteries (n = 40) were studied in vitro with intravascular ultrasound. From each
      vascular specimen, 10 corresponding intravascular ultrasound cross sections
      obtained before and after balloon angioplasty were selected for comparison with
      their histologic counterpart. Morphologic and quantitative data obtained from all
      cross sections were compared with data derived from the most stenotic site. The
      incidence of vascular damage (i.e., dissection, plaque rupture, and media
      rupture) at the most stenotic site was lower than that seen for each vascular
      specimen. The sensitivity of intravascular ultrasound in detecting these
      morphologic features for each vascular specimen was high for dissection and media
      rupture (79% and 76%, respectively), and low for plaque rupture (37%). After
      balloon angioplasty, quantitative changes seen at the most stenotic site were
      greater than those in all cross sections: free lumen area +58% versus +29%, media
      bound area +17% versus +12%, and plaque area reduction -9% versus -6%,
      respectively. The increase in free lumen area was caused predominantly by media
      bound area increase (81%) and to a lesser extent by plaque area decrease (19%).
      This study revealed that a higher incidence of vascular damage is found when the
      whole segment is analyzed rather than 1 single cross section at the most stenotic
      site. Quantitative effects of coronary balloon angioplasty seen with
      intravascular ultrasound were greater at the most stenotic site than at all cross
      sections.

PMID- 7572622
TI  - Changes in electrocardiographic morphology reflect instantaneous changes in left
      ventricular volume and output in cardiac surgery patients.
AB  - We examined the relation between changes in R-to-T wave amplitude ratios (R:T)
      and left ventricular (LV) performance as cardiac output was rapidly varied by
      inferior vena caval occlusion in 6 subjects prior to cardiopulmonary bypass. To
      assess the influence of contractility, paired studies before and after bypass
      were performed in 4 subjects. Stroke volume and cardiac output were assessed by
      aortic flow probe, and transesophageal echocardiographic LV area measures using
      the automated border-detection method were used to give LV stroke area, stroke
      force, maximal LV area, fractional area change, end-systolic elastance, and
      preload recruitable stroke force. Data were collected on computer and analyzed by
      linear regression. Significant changes in R:T and measured LV variables during
      the inferior vena caval occlusion were stroke volume (r = 0.81), LV stroke area
      (r = 0.77), LV stroke force (r = 0.81), maximal LV area (r = 0.78), and cardiac
      output (r = 0.80). However, R:T varied inconsistently in relation to fractional
      area change. After cardiopulmonary bypass, the linear relation between R:T with
      LV stroke force, LV stroke volume, and maximal LV area persisted, but at a lesser
      slope. Although absolute pre-inferior vena caval occlusion R:T did not correlate
      with end-systolic elastance or preload recruitable stroke force, the change in
      the slope of these linear relations correlated well with the change in end
      systolic elastance after surgery (r = 0.92). Instantaneous changes in
      electrocardiographic morphology reflect changes in LV preload-dependent
      variables, whereas long-term changes in electrocardiographic morphology may also
      reflect changes in contractile state.

PMID- 7572623
TI  - Effects of pregnancy on first onset and symptoms of paroxysmal supraventricular
      tachycardia.
AB  - It is important for women to understand the risk of first onset and symptomatic
      exacerbation of paroxysmal supraventricular tachycardia (SVT) during pregnancy.
      Reports regarding the effects of pregnancy on first onset and symptomatic
      exacerbation of paroxysmal SVT have been controversial, and have not been
      conducted in a systematic fashion. Two hundred seven consecutive female patients
      diagnosed with symptomatic paroxysmal SVT were requested to respond to multiple
      questionnaires before electrophysiologic study and catheter ablation. A person
      years data method was used to estimate risk of first onset of paroxysmal SVT
      during pregnancy. Exacerbation of paroxysmal SVT was assessed by a score scale
      including each of the following symptoms: palpitation, fatigue, rest dyspnea,
      effort dyspnea, dizziness, chest oppression, blurred vision, and syncope (total
      score change > 2 points). In the 107 patients with accessory pathway-mediated
      tachycardia, 7 patients had had a first onset of tachycardia during pregnancy
      (relative risk ratio 0.86, confidence interval 0.4 to 1.9, p = 0.35). In the 100
      patients with atrioventricular nodal reentrant tachycardia, 1 patient had had the
      first onset of tachycardia during pregnancy (relative risk ratio 0.11, confidence
      interval 0.02 to 0.56, p = 0.004). Otherwise, 14 of the 63 patients (22%) with
      tachycardia in the pregnant and nonpregnant periods had exacerbation of symptoms
      during pregnancy. Thus, first onset of paroxysmal SVT during pregnancy was rare
      (3.9%), and pregnancy was associated with a low risk of first onset of paroxysmal
      SVT. However, symptoms of paroxysmal SVT were exacerbated during pregnancy in
      some patients.

PMID- 7572624
TI  - Plasma proatrial natriuretic factor is predictive of clinical status in patients
      with congestive heart failure.
AB  - Atrial stretch results in myocyte release of the prohormone atrial natriuretic
      factor (1-126). The N-terminal (1-98) fragment, proatrial natriuretic factor
      (proANF) is released on an equimolar basis with the C-terminal (99-126) active
      hormone and may be assayed simply due to in vitro stability. This study was
      undertaken to evaluate the relation between proANF and routinely available
      measures of clinical status. ProANF was sampled from 202 patients (median age 68
      years [range 15 to 85], 77% men) recruited from an active outpatient heart
      failure clinic. Patients were subgrouped according to New York Heart Association
      functional class, radionuclide ejection fraction (EF), echocardiographic left
      ventricular (LV) end-diastolic diameter, and Doppler-determined systolic
      pulmonary arterial pressure. The median proANF (pmol/L) values for patients in
      New York Heart Association classes I, II, III, IV were 725, 1,527, 1,750, and
      5,172, respectively. The proANF value for the group with EF > 40% was 1,534
      versus 1,993 for EF < or = 40% (p < 0.05). The value for the group with LV
      diameter < 60 mm ws 838 versus 1,751 for LV diameter > or = 60 mm (p < 0.01). The
      value for the group with systolic pulmonary artery pressure < 45 mm Hg was 1,241
      versus 2,660 for systolic pulmonary artery pressure > or = 45 mm Hg (p < 0.01).
      ProANF correlated better than the other variables with New York Heart Association
      functional class and was more closely associated with noninvasive measurements
      than New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7572625
TI  - Exercise capacity and skeletal muscle structure and function before and after
      balloon mitral valvuloplasty.
AB  - This study evaluated the effects of balloon mitral valvuloplasty (BMV) on
      exercise capacity and skeletal muscle structure and function in 10 subjects with
      mitral stenosis (mean age +/- SD 33 +/- 5.5). Measurements were obtained before,
      and 2 weeks and 4 months after BMV to provide baseline data, to examine the
      effects of improved hemodynamics, and to examine the effects of resumption of
      normal physical activity, respectively. Valvuloplasty caused an increase in
      mitral valve area (0.89 +/- 0.04 to 1.75 +/- 0.07 cm2; mean +/- SE), and an
      increase in resting cardiac output (3.8 +/- 0.18 to 4.6 +/- 0.19 L/min, p <
      0.05). At early follow-up after 2 weeks, subjects did more work (31% increase, p
      < 0.01) and had greater maximal oxygen consumption (11% increase, p < 0.01).
      However, measurements reflecting skeletal muscle histology, biochemistry, and
      function were unaltered at this stage. Four months after BMV, subjects had a
      further increase in exercise capacity compared with both baseline (58% increase,
      p < 0.01) and early follow-up (20% increase, p < 0.05). There were associated
      late increases compared with baseline in quadriceps cross-sectional area (66 +/-
      5.8 vs 61 +/- 5.5 cm2, p < 0.05) and torque production (125 +/- 14 vs 118 +/- 16
      Nm, p < 0.05). The percentage of slow twitch type I fibers increased compared
      with baseline (41 +/- 2.0% vs 33 +/- 3.1%, p < 0.05), as did the size of type II
      fibers (5.9 +/- 0.49 vs 4.9 +/- 0.57 microns2 x 10(3), p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572626
TI  - The standard electrocardiogram as a screening test for hypertrophic
      cardiomyopathy.
AB  - Phenotypic heterogeneity in hypertrophic cardiomyopathy (HC) makes definitive
      diagnosis difficult, particularly during family screening. We studied the
      electrocardiogram (ECG) as a potential initial screening test in patients with
      HC. Using accepted diagnostic criteria, we examined the ECGs and echocardiograms
      of 159 patients with a confirmed clinical or genetic diagnosis of HC. An abnormal
      ECG was found in 154 patients (97%) while only 146 (92%) showed an abnormal
      echocardiogram. Of the former, 9 patients (6%) had normal echocardiograms and had
      been diagnosed on the basis of identification of a mutation in the beta myosin
      heavy chain gene (n = 8) or obligate carrier status (n = 1). Only 1 of these 9
      patients was under age 20, the time at which hypertrophy is normally expressed on
      the echocardiogram. The remaining 5 patients (3%) without ECG abnormality
      consisted of 1 patient with an echocardiogram clearly diagnostic of HC and 4
      clinically normal patients (aged 13, 24, 29, and 33 years) with normal
      echocardiograms who had been diagnosed by mutation identification (n = 3) or
      obligate carrier status (n = 1). Thus only these latter 4 patients (3%) would not
      have been diagnosed as having HC based on an abnormal ECG and/or abnormal
      echocardiogram. Screening relatives for HC by ECG criteria alone detects all
      those whom an echocardiogram will diagnose. While echocardiography aids in the
      specificity of HC diagnosis, the ECG, within the context of a family with a
      proven case of HC, is a more sensitive marker of the disease. It is therefore
      both a cost-effective and useful tool for screening those to proceed to
      echocardiography.

PMID- 7572627
TI  - Improvement in noninvasive electrophysiologic findings in children after
      transcatheter atrial septal defect closure.
AB  - To evaluate whether transcatheter closure of secundum atrial septal defects (ASD)
      affected noninvasive electrophysiologic variables in children, we reviewed the
      pre-procedural and 1-year postprocedural electrocardiograms and Holter recordings
      of 18 consecutive children referred for ASD closure. Patients included in the
      study were a mean of 5.0 years old (SD 1.1) and weighed a mean of 17.9 kg (SD
      4.1). ASDs had a mean diameter of 14.0 mm (SD 2.4) and average shunt ratio
      (pulmonary-to-systemic flow) of 2.1:1. One year after occluder device placement,
      9 children (50%) had detectable residual shunts by transthoracic echocardiograms,
      but only 2 (11%) had shunts that were felt to be possibly significant. One or
      more fractured occluder legs were noted by chest roentgenogram in 15 patients
      (83%). Electrocardiograms at follow-up demonstrated improvement in right
      ventricular dilation in 4 of 7 patients, right atrial enlargement in 3 of 4
      patients, and 1 degree atrioventricular block in 2 of 3 patients. Holter
      recordings showed a decreased incidence of accelerated atrial rhythm in 3 of 7
      patients, prolonged junctional escape rhythm in 2 of 2 patients, and premature
      atrial contractions in 2 of 2 patients. No finding correlated with patient age,
      defect or occluder diameter, occluder leg fracture(s), or residual defects. These
      improvements in electrophysiologic abnormalities compare favorably with changes
      seen 1 year after surgical closure. In conclusion, placement of a transcatheter
      ASD device in children diminishes noninvasive electrophysiologic abnormalities at
      1-year follow-up. By relieving hemodynamic stress caused by an ASD in childhood,
      a transcatheter device may prevent arrhythmia disturbance later in life.

PMID- 7572628
TI  - Indexing left ventricular mass to account for differences in body size in
      children and adolescents without cardiovascular disease.
AB  - Left ventricular (LV) mass has been established as an independent risk factor for
      cardiovascular disease morbidity and mortality. To account for differences in
      body size, a variety of factors have been proposed for indexing LV mass. Dual
      energy x-ray absorptiometry provides a measure of lean body mass which can be
      used as a comparison with other more clinically applicable methods of
      standardization. The study included 192 subjects (100 male, 103 white) aged 6 to
      17 years. Lean body mass was determined by dual energy x-ray absorptiometry and
      LV mass was calculated from M-mode echocardiographic measurements. There were
      significant differences by gender (males 98.7 g, females 80.3g, p < 0.001), but
      not race, for unindexed LV mass. Indexing LV mass by lean body mass eliminated
      the difference by gender. Log-log regression analysis revealed that the optimal
      height exponent for indexing LV mass was height3 (95% confidence interval, 2.8 to
      3.1). LV mass/height3 provided the most consistently high intraclass correlation
      with LV mass/lean body mass versus indexing with body surface area, height,
      height2, and height2.7 across the 4 race/gender groups. LV mass indexed by
      height3 eliminated differences in LV mass by gender (males 26.1 +/- 4.72 g/m3,
      females 25.5 +/- 4.8 g/m3, p = NS). The proposed method for indexing LV mass by
      height3 should be useful in the clinical setting. The 90th and 95th percentiles
      of LV mass/height3 provide cutpoints for determining the presence of LV
      hypertrophy in children and adolescents.

PMID- 7572629
TI  - Reduced left ventricular systolic pump performance and depressed myocardial
      contractile function in patients > 65 years of age with normal ejection fraction
      and a high relative wall thickness.
AB  - We studied the relation between relative wall thickness, left ventricular
      systolic pump performance, and myocardial contractile function in 77 older
      patients with normal ejection fraction who were free of valvular and myocardial
      ischemic disease. Group 1 comprised 49 patients with relative wall thickness > or
      = 0.45; group 2 (n = 28) had normal relative wall thickness. Pump performance was
      characterized by stroke volume index, cardiac index, and stroke work; myocardial
      function was characterized by midwall shortening and circumferential stress
      versus shortening relations. Group 1 patients had lower end-diastolic volume (83
      +/- 3 vs 124 +/- 5 ml, p < 0.05), cardiac index (2.6 +/- 0.2 vs 3.5 +/- 0.1
      L/min/m2, p < 0.05), and stroke work/100 g left ventricular mass (43 +/- 2 vs 53
      +/- 3 g-m/100 g, p < 0.005). Although there was no significant difference with
      regard to ejection fraction or fractional shortening at the endocardium,
      fractional shortening at the midwall was significantly lower in group 1 than in
      group 2 (16 +/- 1% vs 19 +/- 1%, p < 0.005). This lower value for midwall
      shortening was observed despite lower values for endsystolic stress, implying
      decreased myocardial contractile function. Lower stroke volume index in group 1
      patients, likely due to small chamber size, was not offset by increased heart
      rate, resulting in a low-normal cardiac index; in 33% of group 1 patients,
      cardiac index was < 2.2 L/min/m2, indicating reduced pump performance. Our data
      indicate an abnormality in pump performance and myocardial function in patients
      who have high relative wall thickness and normal ejection fraction.

PMID- 7572631
TI  - Effect of age on postmyocardial infarction ventricular arrhythmias (Holter
      Registry data from CAST I and CAST II). Cardiovascular Arrhythmia Suppression
      Trials.
AB  - Holter data from the 17,609 postmyocardial infarction patients in the CAST
      Registry were analyzed to study the effect of age on VPC and VT incidence and
      frequency. Multivariable analysis demonstrated that age is an important
      independent predictor of increased ventricular ectopy, with the median rate of
      VPCs/hour increasing from 0.4 (patients aged < 50 years) to 4.0 (patients aged 75
      to 80 years), and the prevalence of VT increasing from 7.3% (patients aged < 50
      years) to 15.3% (patients aged 75 to 80 years).

PMID- 7572632
TI  - Relation between severity of disease and impairment of heart rate variability
      parameters in patients with chronic congestive heart failure secondary to
      coronary artery disease.
AB  - The present data show that HR variability has a statistically significant, but
      moderate, correlation with clinical variables of severity of CHF. Therefore, HR
      variability analysis may be a new, important tool in the clinical assessment of
      CHF patients.

PMID- 7572633
TI  - A distinct electrocardiographic type of acute myocardial infarction determined by
      collateral flow.
AB  - The post-AMI ECG separates patients with ECG changes typical of regional
      pericarditis (Figure 1A) from patients with typical post-AMI changes (Figure 1B).
      The ECG pattern of regional pericarditis identifies a transmural AMI which
      results from a persistent total obstruction of the infarct-related coronary
      artery and inadequate collateral flow.

PMID- 7572630
TI  - Interaction of intravenous heparin and organic nitrates in acute ischemic
      syndromes.
AB  - We evaluated whether a drug interaction between intravenous nitroglycerin or
      isosorbide dinitrate and heparin exists. Ninety-six patients with a diagnosis of
      acute myocardial infarction, unstable angina, or other thromboembolic disorders
      were divided into 3 groups: group I (control group, n = 35) received intravenous
      heparin alone; group II (n = 31) received combined intravenous nitroglycerin and
      heparin; and group III (n = 30) received combined intravenous isosorbide
      dinitrate and heparin. We determined the mean of 2 separate measurements of
      heparin dosage requirement, antithrombin III activity, and the dose of
      intravenous nitroglycerin or isosorbide dinitrate at the time that the ratio of
      activated partial thromboplastin time (aPTT) to baseline aPTT was 1.5 to 2.0. The
      mean therapeutic heparin dose standardized to total body weight of each group was
      13.8, 15.4, and 15.5 U/kg/hour, respectively. At that time, patients were
      receiving intravenous nitroglycerin at doses of 58.8 +/- 38.6 micrograms/min or
      intravenous isosorbide dinitrate at doses of 3.7 +/- 2.0 mg/hour. The mean
      antithrombin III activity of each group was 22.2, 22.8, and 21.3 mg/dl,
      respectively. The overall results for groups I, II, and III, and results for the
      subgroup of patients with acute ischemic syndromes in those groups, did not
      differ significantly. The heparin dose did not show a significant correlation to
      the dose of intravenous nitroglycerin (r = -0.26, p > 0.05) nor to that of
      isosorbide dinitrate (r = 0.30, p > 0.05).

PMID- 7572634
TI  - Increased plasma levels of interleukin-6 and myocardial stunning after coronary
      reperfusion therapy.

PMID- 7572635
TI  - A positive response to head-up tilt testing predicts syncopal recurrence in
      carotid sinus syndrome patients with permanent pacemakers.

PMID- 7572638
TI  - Missed diagnosis of severe symptomatic aortic stenosis.
AB  - Patients with angina pectoris and congestive heart failure with a systolic murmur
      should be suspected of having significant AS. These patients are frequently women
      with atrial fibrillation and no left ventricular hypertrophy criteria on the
      electrocardiogram. Echocardiography with calculation of the aortic valve area is
      indicated in all these patients.

PMID- 7572636
TI  - Is the pulmonary venous-transmitral A-wave duration difference altered by age and
      hypertension?
AB  - We have demonstrated that the pulmonary venous and transmitral atrial duration,
      and the difference between the 2 are independent of age and not influenced by
      hypertension, but have a high interobserver variability and range of variability.
      Enthusiasm for this parameter with the currently available recording techniques
      must be tempered by the high variability in this measurement.

PMID- 7572637
TI  - Accuracy of quantitation of aortic stenosis using femoral arterial recordings
      corrected for both temporal delay and systolic amplification.
AB  - Our study demonstrates the feasibility of substituting FA recordings, corrected
      for both temporal delay and systolic amplification, for central aortic recordings
      in assessing aortic valve stenosis. This method is accurate in estimating the
      transaortic valve gradient, the calculated valve area, and the calculated valve
      resistance, and obviates the risks and costs of 2 FA punctures.

PMID- 7572639
TI  - Pulmonary vein Doppler flow patterns specific for elevated left ventricular
      filling pressures in older cardiac patients are common in healthy adults < 40
      years old.
AB  - In older cardiac patients, elevated left-sided heart filling pressures are
      predicted by both a systolic PV flow fraction < 40% and a greater duration during
      atrial systole of reversal flow into the PVs than forward flow through the mitral
      valve. However, this study shows that these Doppler findings are not uncommon in
      younger subjects without cardiac disease. Use of these PV Doppler flow parameters
      to assess LV filling pressures should be limited to older patients.

PMID- 7572641
TI  - Diagnosis of aortic intramural hematoma by intravascular ultrasound imaging.
AB  - Our findings indicate the value of IVUS in the study of aortic intramural
      hematomas in ruling out other aortic diseases such as classic aortic dissection.
      This technique appears especially attractive for patients with suspected aortic
      dissection and a normal aortography.

PMID- 7572642
TI  - Recurrence of primary (AL) amyloidosis in a transplanted heart with four-year
      survival.
AB  - Cardiac amyloidosis has a poor prognosis, with a median survival of approximately
      6 months once symptoms develop. This patient had a markedly improved quality of
      life with cardiac transplantation. We would suggest that with refinement of
      pretransplant chemotherapy, prolonged survival may be possible in carefully
      selected cases.

PMID- 7572640
TI  - Management of stroke complicating cardiac catheterization with recombinant tissue
      type plasminogen activator.

PMID- 7572643
TI  - Implantable cardioverter-defibrillator dysfunction after coronary artery bypass
      grafting.
AB  - Displacement of an ICD electrode is a possible complication after changes in
      heart size after CABG and simultaneous implantation of an epicardial lead ICD. To
      prevent potentially life-threatening ICD dysfunction in patients who are
      candidates for CABG and ICD implantation, we suggest the use of transvenous ICD
      systems or a staged procedure (CABG followed by ICD implantation) rather than a
      simultaneous operation.

PMID- 7572644
TI  - Long QT syndrome associated with syndactyly identified in females.
AB  - The identification of female children with this syndrome is evidence that this
      disorder is not X-linked in inheritance. Possible inheritance modes still include
      autosomal recessive or, more likely, a de novo mutation, given the absence of
      family history in any of the patients. Children of both sexes with syndactyly
      should be screened with an electrocardiogram for this syndrome. Female children
      with this syndrome may have an increased risk of sudden death similar to male
      children.

PMID- 7572646
TI  - Dysfunction of small coronary vessels in hypertensive patients with normal
      angiograms.

PMID- 7572647
TI  - Effect of interleukin-3 on lipoprotein(a) and lipoprotein cholesterol levels.

PMID- 7572645
TI  - Repolarization revisited.

PMID- 7572648
TI  - Incomplete recanalization as an important determinant of Thrombolysis in
      Myocardial Infarction (TIMI) grade 2 flow after thrombolytic therapy for acute
      myocardial infarction. TEAM Investigators. Thrombolytic Trial of Eminase in Acute
      Myocardial Infarction.
AB  - The outcome of patients with Thrombolysis in Myocardial Infarction (TIMI) trial
      grade 2 flow is worse than that of patients with TIMI grade 3 flow after
      thrombolytic therapy for acute myocardial infarction. It is unclear whether TIMI
      grade 2 flow represents incomplete recanalization of the culprit lesion or poor
      distal runoff. The Thrombolytic Trial of Eminase (anistreplase) in Acute
      Myocardial Infarction (TEAM)-2 and TEAM-3 were randomized trials comparing
      anistreplase with streptokinase (TEAM-2, n = 370) or with alteplase (tissue
      plasminogen activator) (TEAM-3, n = 325). We compared the minimal luminal
      diameter of the culprit lesion in patients with TIMI grade 2 flow with that in
      patients with TIMI grade 3 flow both 90 minutes (TEAM-2) and 1 day (TEAM-3) after
      thrombolysis. Patients with TIMI grade 2 flow had a lower residual luminal
      diameter in the culprit lesion than patients with TIMI grade 3 flow (TEAM-2, 0.58
      +/- 0.03 vs 0.79 +/- 0.02 mm, p = 0.0001; TEAM-3, 0.88 +/- 0.04 vs 1.17 +/- 0.03
      mm, p = 0.0001, for patients with TIMI grades 2 and 3 flow). Residual percent
      stenosis was correspondingly higher in patients with TIMI grade 2 flow. At the
      early angiogram, 66% of patients with TIMI grade 2 flow, but only 35% of those
      with TIMI grade 3 flow, had a minimal luminal diameter of 0.6 mm (positive
      predictive value 87%, negative predictive value 35%). Incomplete recanalization
      of the culprit lesion may thus be an important determinant of TIMI grade 2 flow
      after thrombolysis. Whether more complete thrombolysis or rescue angioplasty
      improves outcome in these patients deserves evaluation.

PMID- 7572651
TI  - Effect of early enalapril therapy on left ventricular function and structure in
      acute myocardial infarction.
AB  - Infarct expansion starts within hours to days after transmural myocardial injury.
      Previous echocardiographic and left ventriculographic studies demonstrated that
      angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular
      dilatation, particularly in patients with anterior wall acute myocardial
      infarction (AMI) or impaired left ventricular function. Forty-three patients with
      an acute Q-wave AMI were randomized within 24 hours of symptom onset to
      intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding
      oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans
      were obtained in 32 patients to evaluate changes in cardiac volumes and ejection
      fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month
      to evaluate left ventricular infarct expansion. Blood pressure decreased at 6
      hours but returned to baseline in both groups after 1 month of therapy. The
      change in cardiac volumes from baseline to 1 month differed between the placebo
      (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and
      enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml)
      groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved
      significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%,
      respectively) but did not change over 1 month in the placebo group. Infarct
      segment length and infarct expansion index by magnetic resonance imaging were
      significantly less in those treated with enalapril, suggesting less infarct
      expansion in this group. Thus, early administration of enalaprilat to patients
      presenting with a first Q-wave AMI prevents cardiac dilatation and infarct
      expansion.

PMID- 7572650
TI  - Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs
      diltiazem) in patients with stable angina pectoris.
AB  - We investigated whether analysis of heart rate (HR) variability may be used to
      predict the efficacy of drug treatment of myocardial ischemia. In a double-blind,
      crossover study, 28 patients with stable angina pectoris, proven coronary artery
      disease, and myocardial ischemia during Holter monitoring received metoprolol
      controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a
      placebo run-in phase and after each treatment period, 72-hour Holter recordings
      were obtained for HR variability and ST-segment analysis. At baseline, the total
      duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24
      hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol
      significantly reduced the total duration of ischemia by -8.7 minutes (95% CI 
      14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients
      with a low SD of normal-to-normal intervals at baseline (SDNN), using the median
      value of 50 ms as a cut-off value. In contrast, significant treatment effects
      were not observed in patients with a high SDNN at baseline. Similar results were
      obtained using baseline total power or low-frequency power, but not when using
      baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9
      minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to
      metoprolol, efficacy of diltiazem was not related to baseline HR variability. In
      conclusion, patients with reduced HR variability at baseline responded to
      treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572649
TI  - Nonlimited exercise test combined with high-dose dipyridamole for thallium-201
      myocardial single-photon emission computed tomography in coronary artery disease.
AB  - Clinical, electrocardiographic, and thallium-201 single-photon emission computed
      tomography data were evaluated in 397 consecutive patients divided into 3 groups
      according to coronary hyperemic stimulation: 186 patients (group I; Ex) had
      maximal symptom-limited exercise ergometric stress testing, 93 patients (group
      II; Dip) had intravenous dipyridamole (0.7 to 0.8 mg/kg) stress testing, and 118
      patients (group III; Dip+Ex) had dipyridamole (0.7 to 0.8 mg/kg) plus nonlimited
      (i.e., symptom-limited) exercise stress testing, achieving a maximal workload
      (mean +/- SD) of 102 +/- 37 W. Clinical tolerance was higher in Ex than in Dip
      groups (p < 0.01), and tended to be higher in Dip+Ex than in Dip groups (p = NS).
      Image quality--as judged by signal-to-noise ratios--was superior in Ex and Dip+Ex
      groups when compared with the Dip group (p < 0.01). Chest pain and
      electrocardiographic positivity were more frequent in the Dip+Ex group than in
      the Dip group (p < 0.05), despite more extensive coronary artery disease (CAD) in
      the Dip group; and reversible scintigraphic defects were more frequent in Dip+Ex
      versus Dip (p < 0.01) and in Ex versus Dip groups (p < 0.05) in patients with
      established CAD, as well as for the whole group. We conclude that, in patients
      unable to achieve 85% of their maximal predicted heart rate, the combination of
      high-dose dipyridamole plus nonlimited exercise stress testing is superior to
      dipyridamole stress testing alone, and comparable to maximal exercise testing.

PMID- 7572652
TI  - Impact of intensive physical exercise and low-fat diet on collateral vessel
      formation in stable angina pectoris and angiographically confirmed coronary
      artery disease.
AB  - This randomized study was performed to assess the effects of > 3 hours of
      physical exercise per week and low-fat diet on collateral formation in
      nonselected patients with coronary artery disease (intervention group, n = 56).
      Results were compared with those of patients in a control group (n = 57), who
      received usual care by their private physicians. Coronary lesions were assessed
      by quantitative coronary angiography at the beginning and after 1 year of study
      (n = 92). As previously reported, after 1 year there was a significant
      retardation of progression of coronary artery disease in the intervention group
      as compared with the control group. In this study, evaluation of collateral
      formation revealed no significant difference between both groups, and changes in
      hemodynamic and metabolic variables or leisure time physical activity were not
      related to changes in collateral formation. Although progression of the disease
      was significantly related to an increase in collateral formation, regression was
      significantly related to a decrease in collateral formation (p < 0.00001).
      Because patients in the intervention group exercised for > 3 hours/week, and
      patients with regression of coronary artery disease even dedicated 5 to 6 hours
      to leisure time physical activity per week, these findings question whether an
      exercise program within the safety tolerance of patients will be able to induce
      coronary collateralization in the presence of regression of coronary artery
      disease.

PMID- 7572654
TI  - Incidence and electrocardiographic localization of safe right bundle branch block
      configurations during permanent ventricular pacing.
AB  - The usual morphology for paced events originating from the right ventricle has a
      left bundle branch block (BBB) pattern. However, in a few patients, right BBB
      configurations are identified. It is important to differentiate safe right BBB
      patterns from those caused by septal or free wall perforation. Paced
      electrocardiograms were examined in 179 consecutive patients who underwent
      pacemaker placement. Fourteen patients (8%) were identified with right BBB
      configurations. Posteroanterior and lateral chest radiographs and echocardiograms
      were evaluated specifically to identify the pacing lead location in this group.
      In addition, 152 paced episodes from published reports were combined with our
      population to create an electrocardiographic algorithm differentiating right
      ventricular septum, right ventricular apex, coronary venous, and left ventricular
      pacing. Chest radiographs and echocardiographic lead locations correlated
      perfectly in the 11 patients available for echocardiograms. With use of a left
      superior axis and precordial transition by lead V3, right ventricular right BBB
      morphologies were correctly detected in 18 of 21 patients (86% sensitivity, 99%
      specificity) and appropriately separated from left ventricular pacing in 18 of 19
      patients (95% positive predictive value). Therefore, 12-lead electrocardiograms
      are a rapid, reliable means of separating right and left ventricular right BBB
      pacing morphologies. Prudent use of these criteria will help eliminate
      unnecessary echocardiography, anticoagulation, and lead revision.

PMID- 7572653
TI  - Safety and efficacy of extended urokinase infusion plus stent deployment for
      treatment of obstructed, older saphenous vein grafts.
AB  - This study was designed to determine the safety and efficacy of extended,
      continuous infusion of urokinase plus stent deployment to treat older saphenous
      vein bypass grafts obstructed by both thrombus and atheromatous material. Thirty
      patients with angiographic evidence of thrombus and atheromatous material
      obstructing older vein grafts (mean age 8.3 years) underwent the combined
      interventions of urokinase infusion and stent deployment. The continuous infusion
      of urokinase was administered directly into each obstructed vein graft over a
      mean of 20.5 +/- 8.1 hours (median dose 2.2 +/- 0.7 million units). Stents were
      deployed at the sites of atheromatous obstruction either before (5 patients) or
      after (25 patients) infusion of urokinase. Twenty-eight of the 30 patients were
      successfully treated with the combined interventions (success rate 93.3%). In
      these 28 patients, percent diameter stenosis at the site of obstruction decreased
      from 86.0% to -0.2% and Thrombolysis in Myocardial Infarction trial flow
      increased from 1.0 to 2.5. Two patients (6.7%) developed stent thrombosis
      followed by myocardial infarction (1 with Q-wave infarction, 3.3%) and congestive
      heart failure. Minor complications included non-Q-wave myocardial infarction (5
      patients, 16.7%) and access-site hemorrhage (5 patients, 16.7%). At 2-week follow
      up, anginal symptoms were decreased in all 28 successfully treated patients. At
      7.2 +/- 3.7-month follow-up, 5 of the 28 successfully treated patients (17.9%)
      had reacceleration of angina and angiographically documented restenosis at the
      site of stent deployment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572655
TI  - Effect of total adipose weight and systemic hypertension on left ventricular mass
      in children.
AB  - To investigate the effect of obesity and hypertension on left ventricular (LV)
      mass in children, we performed echocardiography and measured the height, weight,
      and blood pressure of 267 healthy children (145 boys and 122 girls) aged 12
      years. The percentage of body fat was estimated using bioelectric impedance to
      derive the total adipose weight and lean body weight. End-diastolic measurements
      of LV parameters were obtained from M-mode echocardiograms. The LV mass was
      calculated by using the formula of Devereux et al. A strong positive correlation
      was demonstrated between non-normalized LV mass and height or other measures of
      body size. Systolic blood pressure was weakly correlated with non-normalized LV
      mass in boys. The impact of height on LV mass differed between boys and girls.
      Thus, different allometric formulas to normalize the LV mass for height were
      determined, using the height to the 3.1 and 1.9 powers for boys and girls,
      respectively. Regression analysis revealed that only total adipose weight
      affected the normalized LV mass, and that the effect of total adipose weight was
      greater in girls than in boys. The obese children had a significantly greater
      normalized LV mass than the nonobese children. The increase in the LV mass due to
      obesity appeared to be eccentric, because of the lack of an association between
      the indices of obesity and relative wall thickness. Our data indicate that
      appropriate normalization of LV mass is necessary for each study population, and
      that LV hypertrophy due to obesity begins in childhood.

PMID- 7572656
TI  - Relation of the nine-minute self-powered treadmill test to maximal exercise
      capacity and skeletal muscle function in patients with congestive heart failure.
AB  - The 9-minute self-powered treadmill test has been employed to evaluate submaximal
      exercise capacity in heart failure patients, but its relation to maximal exercise
      capacity and to indexes of skeletal muscle function has not been well defined.
      Two protocols were utilized. The first evaluated the relation of the peak oxygen
      uptake (VO2) achieved on the self-powered treadmill to that during a symptom
      limited treadmill protocol, and examined the reproducibility of this test.
      Thirteen patients (aged 62 +/- 2 years, in New York Heart Association class I to
      III [2.3 +/- 0.1], ejection fraction 23 +/- 2% [means +/- SEM]) and 10 age
      matched sedentary controls were studied. The second protocol, which involved 18
      patients (aged 65 +/- 2 years, in New York Heart Association class I to IV [2.4
      +/- 0.1], ejection fraction 23 +/- 2%) and 10 age-matched controls evaluated the
      relation of performance on the self-powered treadmill to maximal systemic
      exercise capacity on a cycle ergometer and to indexes of skeletal muscle
      function. In the first protocol, the test was found to be highly reproducible.
      The proportion of self-powered treadmill to maximal treadmill peak VO2 did not
      differ significantly between patients and controls (95 +/- 5% vs 87 +/- 6%). In
      the second protocol, patients achieved a lower peak VO2 (15.6 +/- 1.1 vs 25.6 +/-
      0.9 ml/kg/min, p < 0.001), walked a shorter distance on the self-powered
      treadmill (367 +/- 32 vs 667 +/- 28 m, p < 0.001), and exhibited less knee
      extensor work capacity (1,075 +/- 116 vs 1,390 +/- 110 ft-lbs, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572657
TI  - Lung-heart interaction as a substrate for the improvement in exercise capacity
      after body fluid volume depletion in moderate congestive heart failure.
AB  - We investigated exercise capacity after fluid depletion in patients with moderate
      congestive heart failure (CHF). Twenty-one patients underwent ultrafiltration
      (mean volume +/- SEM: 1,770 +/- 135 ml). Echocardiography, tests of pulmonary
      function, and a cardiopulmonary exercise test with hemodynamic and esophageal
      pressure monitoring were performed before ultrafiltration and 3 months later.
      Tests without invasive measurements were repeated 4 and 30 days after
      ultrafiltration. Twenty-one control patients followed the same protocol but did
      not have ultrafiltration. Patients who underwent ultrafiltration and increased
      their oxygen consumption at peak exercise (peak VO2) by > 10% at the 3-month
      evaluation (group A1, n = 9) were separated from those who did not (group A2, n =
      8); 3 patients did not complete the follow-up. Four days after the procedure,
      peak VO2 had risen from 17.3 +/- 0.8 to 19.3 +/- 0.9 ml/min/kg in group A1, and
      from 11.9 +/- 0.7 to 14.1 +/- 0.7 ml/min/kg in group A2 (p < 0.01). Plasma
      norepinephrine and pulmonary function were consistent with a greater severity of
      the syndrome in group A2. At 3 months in group A1, the relations of filling
      pressure to cardiac index of the right and left ventricles were shifted upward;
      the esophageal pressure swing (differences between end-expiratory and end
      inspiratory pressure) for a given tidal volume was lower; the peak exercise
      dynamic lung compliance had increased from 0.10 +/- 0.05 to 0.14 +/- 0.03 L/mm Hg
      (p < 0.01). None of these changes were detected in group A2 and control
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572658
TI  - Excessive oxygen deficit during low-level exercise in heart failure.
AB  - Although peak oxygen consumption is reduced in patients with symptomatic heart
      failure, the degree of limitation during routine activity often appears greater
      or lesser than expected from peak capacity. This study was undertaken to
      determine whether abnormalities could be detected during the initiation of steady
      state low-level exercise, approximating routine activity, which were distinct
      from limitation in peak capacity. We sought to determine whether a delay in the
      integrated response to the increased metabolic demand caused by exercise,
      assessed by the oxygen deficit incurred between exercise initiation and the
      achievement of steady-state oxygen uptake, was present in heart failure. Low
      level and symptom-limited maximal exercise tests in 33 ambulatory patients with
      heart failure were analyzed and compared with 9 tests in control subjects. Oxygen
      deficit was determined during the 8-minute low-level exercise at 20 W. During
      maximal exercise, as expected, patients with heart failure had lower peak oxygen
      uptake (16 +/- 4 vs 31 +/- 6 ml/kg/min) and anaerobic threshold (870 +/- 270 vs
      1,180 +/- 370 ml/min) than controls. After 8 minutes of low-level exercise, the
      oxygen deficit was higher in patients than in controls (550 +/- 230 vs 270 +/-
      100 ml, respectively, p < 0.01). Among patients with heart failure, the oxygen
      deficit did not correlate with peak oxygen uptake or anaerobic threshold.
      Although the time to steady-state heart rate was later in patients with heart
      failure, this delay did not correlate with oxygen deficit. The oxygen deficit
      represents a distinct abnormality of exercise response that may reflect impaired
      central and peripheral responses to the initiation of exercise.

PMID- 7572660
TI  - Management of hypoplastic left heart syndrome in a consortium of university
      hospitals.
AB  - To determine current management of hypoplastic left heart syndrome, we utilized
      the discharge database of the University Hospital Consortium and obtained data on
      the surgical procedures, length of stay, hospital charges, and outcome for 636
      neonates with this condition admitted to 40 member institutions from 1989 to
      1993. Of the 636 patients, 95 (15%) were discharged without surgical
      intervention. A Norwood operation was performed in 222 (53% mortality) and
      transplantation in 40 (42% mortality). Median length of stay and hospital charges
      were 17 days and $57,418 for the Norwood procedure and 47 days and $126,695 for
      transplantation.

PMID- 7572659
TI  - Prognostic value of plasma soluble intercellular adhesion molecule-1 and
      endothelin-1 concentration in patients with chronic congestive heart failure.
AB  - We tested the hypothesis that plasma endothelin-1 (ET-1) and soluble
      intercellular adhesion molecule-1 (sICAM-1) in patients with congestive heart
      failure (CHF) are related to subsequent survival, and assessed whether the
      measurements of these substances provide additional prognostic information to
      that obtained from clinical and biochemical variables previously known to be
      associated with high mortality. Plasma levels of sICAM-1 and ET-1 were measured
      in 102 patients with CHF (left ventricular ejection fraction [LVEF] < 0.45), and
      patients were followed up for > 18 months. The plasma level of sICAM-1 increased
      with the severity of CHF (normal, 149 +/- 10 ng/ml, mild CHF [New York Heart
      Association functional class II], 207 +/- 9.4 ng/ml, severe CHF [functional class
      III or IV], 293 +/- 18 ng/ml). The plasma level of ET-1 also increased with the
      severity of CHF (normal, 1.5 +/- 0.2 pg/ml, mild CHF, 2.1 +/- 0.1 pg/ml, severe
      CHF, 4.0 +/- 0.4 pg/ml). Plasma levels of both sICAM-1 and ET-1 decreased after
      treatment in 14 patients, with improvements in symptoms (from functional class IV
      to II) during the follow-up period. There was a significant positive correlation
      between the plasma level of ET-1 and plasma sICAM-1 (r = 0.44, p < 0.001). A
      significant negative correlation was observed between LVEF and plasma ET-1 (r = 
      0.34, p < 0.001), and plasma sICAM-1 (r = -0.36, p < 0.001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7572661
TI  - Heart rate to work rate relation throughout peak exercise in normal subjects as a
      guideline for rate-adaptive pacemaker programming.
AB  - We investigated the physiologic heart rate (HR) to work rate (WR) relation
      throughout peak exercise in normal subjects as a guideline for rate-adaptive
      pacemaker slope programming. The study group consisted of 41 middle-aged subjects
      (22 men and 19 women) without evidence of cardiopulmonary disease. Peak-exercise
      stress tests were performed on a calibrated treadmill by using the symptom
      limited "ramping incremental treadmill exercise" (RITE) protocol. The HR
      response, oxygen uptake, and treadmill workload increments were assessed
      simultaneously. The HR/WR slope, as determined using linear regression analysis,
      was 0.37 +/- 0.13 beats/min/W for the entire study group, which indicates an
      upper range increase of 5 beats/10 W increase of external treadmill work
      performed, using the mean value +/- 1 SD. Men generated an HR/WR slope of 0.32 +/
      0.09 beats/min/W, and women, 0.43 +/- 0.15 beats/min/W, indicating a significant
      sex-related difference in the HR/WR relation (p < 0.01). Thus, to achieve an
      appropriate matching of HR with patient effort, rate-adaptive pacemakers should
      generate an average increase of approximately 5 beats per increase in 10 W of
      external treadmill work. The HR/WR relation can easily be determined to provide
      the clinician with a minimal check system to avoid a hyper- or hypochronotropic
      paced response to exercise.

PMID- 7572662
TI  - Adenosine radionuclide perfusion imaging in the preoperative evaluation of
      patients undergoing peripheral vascular surgery.
AB  - To define the clinical and adenosine test variables that predicted perioperative
      cardiac events, 122 patients who received adenosine radionuclide perfusion
      imaging before peripheral vascular surgery were reviewed. Events included
      pulmonary edema, an ischemic end point of acute myocardial infarction (AMI) or
      cardiac death. Five patients underwent coronary revascularization before the
      surgical procedure. Of the 117 remaining patients, 19 had pulmonary edema, 10 had
      an AMI, and 2 died after peripheral vascular surgery. Most of the patients (78%)
      were in an intermediate-risk group as indicated by the presence of > or = 1
      clinical risk factor as defined by the Eagle criteria. The only predictor of
      perioperative pulmonary edema was a history of congestive heart failure (33% vs
      4%; p = 0.002). No clinical variables predicted AMI or death. The adenosine
      variables that were univariate predictors of AMI and death were the number of
      reversible perfusion defects (1.75 +/- 1.84 vs 0.75 +/- 0.90; p = 0.001) and the
      number of coronary artery distributions with a radionuclide perfusion defect
      (1.33 +/- 0.64 vs 0.85 +/- 0.67; p = 0.022). The number of reversible perfusion
      defects was the only multivariate predictor of ischemic events (p = 0.017). The
      presence of > 1 reversible defect was associated with an increased frequency of
      ischemic events (68% vs 28%; p = 0.045). The sensitivity and specificity of > 1
      reversible defect was 58% and 73%, respectively, with a positive and negative
      predictive value of 19% and 94%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572663
TI  - Usefulness of adjunctive angioscopy and extraction atherectomy before stent
      implantation in high-risk aortocoronary saphenous vein grafts.

PMID- 7572664
TI  - Stroke risk after anterior wall acute myocardial infarction. SPRINT Study Group.
      Secondary Prevention Reinfarction Israeli Nifedipine Trial.

PMID- 7572665
TI  - Prethrombolytic versus thrombolytic era risk stratification of patients with
      acute myocardial infarction.

PMID- 7572666
TI  - A cost-effective analysis of primary coronary angioplasty versus thrombolysis for
      acute myocardial infarction.

PMID- 7572668
TI  - Clinical course of lone atrial fibrillation since first symptomatic arrhythmic
      episode.

PMID- 7572667
TI  - Role of transthoracic, transesophageal, and transgastric two-dimensional and
      color Doppler echocardiography in the evaluation of mechanical complications of
      acute myocardial infarction.

PMID- 7572669
TI  - Left atrial appendage function in patients with single-chamber ventricular
      pacing.

PMID- 7572670
TI  - Obstruction of the proximal pulmonary artery branches after banding of the
      pulmonary trunk.

PMID- 7572671
TI  - Analysis of visceral heterotaxy according to splenic status, appendage
      morphology, or both.

PMID- 7572672
TI  - The role of limited echocardiography in screening athletes.

PMID- 7572673
TI  - Cardiovascular safety of maximal strength testing in healthy adults.

PMID- 7572675
TI  - Concerning the angina of "syndrome X".

PMID- 7572674
TI  - Real-time comparison of pressure-predicted and Doppler-measured jet velocities
      distal to left-sided obstructions throughout systole.

PMID- 7572676
TI  - Theoretical aspect of effective antiarrhythmic therapy: ventricular arrhythmia
      and drugs that prolong action potential duration (APD)

PMID- 7572677
TI  - Cholesterol reduction and its impact on coronary artery disease and total
      mortality.
AB  - A sample of 42 randomized cholesterol-lowering trials represented by 32 data
      points were subjected to a metaregression analysis. The logarithmic odds ratio
      (InOR) of total mortality outcome or incidence of coronary artery disease (CAD)
      were used as dependent variables and regressed against the net amount of total
      cholesterol reduction between treatment groups in each trial. Analyses were
      weighted by variance of OR. Adjustments were also made for single and multifactor
      trials and for total mortality risk level in the control/placebo group as well as
      for treatment modality. Analyses were performed both with and without inclusion
      of trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors as treatment modality. A statistically significant dose-response
      relationship was found between InOR and the amount of cholesterol reduction for
      both endpoints and in both groups of trials. These findings were essentially
      unaltered by various adjustments for potential confounders or by various
      sensitivity analyses. The results of the Scandinavian Simvastatin Survival Study
      (4S) fell close to the regression lines for both outcome measures, and inclusion
      of other statin trials strengthened the significance of this dose-response
      compared with previous metaregression analyses without inclusion of statin
      trials. The type of treatment was significantly associated with both endpoints.
      Fibrate trials did significantly worse on all-cause mortality than statin trials
      and other drug trials (except hormone). The baseline cholesterol level was also
      significantly predictive of CAD incidence as a trial outcome; efficacy increased
      with increased level of baseline cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572679
TI  - The West of Scotland Coronary Prevention Study: a trial of cholesterol reduction
      in Scottish men.
AB  - The West of Scotland Coronary Prevention Study is a primary prevention trial
      designed to test the hypothesis that reduction of serum cholesterol with
      pravastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) over an
      average of 5 years will reduce the incidence of fatal and nonfatal myocardial
      infarction. At entry, 6,595 men aged 45-64 years were randomized to treatment
      with either pravastatin (40 mg/day) or placebo. None of the men at entry had
      evidence of previous myocardial infarction. All were given smoking and dietary
      advice throughout the study, which will terminate in 1995. The principal
      endpoints are: (1) death due to coronary artery disease (CAD) plus nonfatal
      myocardial infarction; (2) death due to CAD; and (3) nonfatal myocardial
      infarction.

PMID- 7572678
TI  - Management of the Long-Term Intervention with Pravastatin in Ischaemic Disease
      (LIPID) study after the Scandinavian Simvastatin Survival Study (4S).
AB  - The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study
      was designed when considerable disagreement existed as to relative benefits and
      risks of cholesterol reduction. Between June 1990 and December 1992, 9,014
      patients aged 31-75 years were randomized to receive either pravastatin 40 mg
      once daily or placebo. These patients had experienced either acute myocardial
      infarction or unstable angina within the preceding 3 months to 3 years and had
      total cholesterol levels of 155-271 mg/dl (4.0-7.0 mmol/liter). All patients
      received dietary advice. The LIPID study is projected for conclusion in 1997,
      after a follow-up period of at least 5 years. The primary study endpoint is
      mortality due to coronary artery disease (CAD). The Scandinavian Simvastatin
      Survival Study (4S) is the first secondary prevention trial to show a reduction
      in total mortality with lipid-lowering therapy. However, the LIPID study should
      continue for the following reasons: (1) important differences exist between the
      LIPID study and 4S cohorts. Overall, > 80% of the LIPID patients could not have
      been included in 4S on the basis of their cholesterol level, age, or history of
      CAD; (2) the LIPID study will also provide important information on noncoronary
      mortality and on other groups, such as women and diabetic patients, who have been
      underrepresented in previous trials; (3) the LIPID study design allows for
      clinical management, including lipid-lowering therapy, to be at the discretion of
      the physician managing a trial patient. The 4S results have been brought to the
      attention of all LIPID investigators, Institutional Ethics Committees, the
      physicians of the individual patients, and the patients themselves.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572680
TI  - Extending the benefit of lipid-regulating therapy to primary prevention.
AB  - In recent years, a number of published secondary prevention trials have further
      strengthened the rationale for aggressive lipid-regulating therapy in patients
      with established coronary artery disease. However, the role of lipid-regulating
      therapy in primary prevention is less well characterized. Several large primary
      prevention trials, using a variety of interventions, are ongoing in different
      populations. These include the Air Force Coronary/Texas Atherosclerosis
      Prevention Study, the West of Scotland Coronary Prevention Study, the Women's
      Health Initiative, and the Antihypertensive and Lipid-Lowering Treatment to
      Prevent Heart Attack Trial. These investigations will extend the results of
      earlier primary prevention trials and further characterize the rationale for
      intervention.

PMID- 7572681
TI  - Prospective meta-analysis of cholesterol-lowering studies: the Prospective
      Pravastatin Pooling (PPP) Project and the Cholesterol Treatment Trialists (CTT)
      Collaboration.
AB  - Meta-analyses of randomized trials evaluating cholesterol-lowering therapy have
      demonstrated clear reductions in coronary events and coronary mortality. However,
      the treatment impact on total mortality has been less certain. With the variable
      selection of trials and treatment questions, results of meta-analyses have
      sometimes given conflicting conclusions regarding the magnitude of treatment
      effects and the populations to whom benefits might accrue. Prospective meta
      analysis can avoid these problems by clearly specifying the research questions,
      eligible studies, analysis plans, and outcome definitions in advance of trial
      results publication. This approach has been adopted in 2 major prospective meta
      analyses of cholesterol-lowering treatments: the Prospective Pravastatin Pooling
      (PPP) project and the Cholesterol Treatment Trialists (CTT) collaboration. The
      PPP project is a prospectively planned combined analysis of 3 large-scale
      pravastatin trials comparing pravastatin against placebo over a minimum 5-year
      period. The analysis will contain data for > 19,500 patients and should have the
      power to examine the effects of treatment on total mortality, coronary mortality,
      and incidence of cancers as well as the ability to look at total coronary events
      in important subgroups underrepresented in previous trials. The CTT collaboration
      is a planned prospective meta-analysis of 12 major ongoing or planned randomized
      trials evaluating therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors, a fibrate, or dietary modification. The trials were prospectively
      registered and the CTT protocols became final in November 1994. By the year 2000,
      the CTT collaboration is projected to have information on about 65,000
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572683
TI  - Elucidation of the role of plaque instability and rupture in acute coronary
      events.
AB  - The basic mechanisms of atherosclerotic progression have been well elucidated
      during the last few years. In this brief presentation on the acute coronary
      syndromes, the fate of plaque rupture and our understanding of "passive" versus
      "active" rupture are defined. In addition to the phenomenon of plaque rupture,
      the thrombogenicity of atherosclerotic plaques in the genesis of coronary
      syndromes is defined. The combination of plaque disruption and high thrombogenic
      risk profile--including local and systemic factors--is vital to understanding the
      genesis of the acute coronary syndromes.

PMID- 7572682
TI  - Pathogenesis of atherosclerosis.
AB  - The earliest lesion in the development of an atherosclerotic plaque is the fatty
      streak. This chronic inflammatory reaction results from a sequence of events that
      begins with the trapping of low density lipoprotein (LDL) in the subendothelial
      space of the artery wall. The trapped LDL is seeded with oxidative species
      released by the overlying endothelium, and lipid oxidation is initiated within
      the LDL particle. Some of the lipids that result lead to the activation of NFkB
      like transcription factors that cause the expression of genes whose protein
      products mediate monocyte binding, monocyte chemotaxis into the subendothelial
      space, and conversion into macrophages. At least 1 major gene modulates the
      oxidation of LDL lipids and/or the biologic response to these lipids. The inverse
      relation between high density lipoprotein (HDL) and atherosclerotic events may in
      part be due to enzymes associated with HDL that destroy the biologically active
      lipids generated in LDL.

PMID- 7572684
TI  - The Kuopio Atherosclerosis Prevention Study (KAPS): effect of pravastatin
      treatment on lipids, oxidation resistance of lipoproteins, and atherosclerotic
      progression.
AB  - The Kuopio Atherosclerosis Prevention Study is the first population-based, double
      blind trial in the primary prevention of carotid and femoral atherosclerosis. A
      total of 447 subjects with serum low density lipoprotein (LDL) cholesterol levels
      > or = 155 mg/dl (> or = 4.0 mmol/liter) and total cholesterol levels < 290 mg/dl
      (< 7.5 mmol/liter) were randomly assigned to receive either pravastatin 40 mg/day
      or placebo for 3 years. Atherosclerotic progression in 424 men was assessed with
      B-mode ultrasonography. Pravastatin reduced the rate of progression by 45% (95%
      confidence interval [CI]: 16-69%, p = 0.005) in carotid arteries and by 66% (95%
      CI: 30-90%, p = 0.002) in the common carotid arteries. The treatment effect in
      the carotid arteries was greater in subjects with thick arterial walls at
      baseline, in smokers, and in subjects with low plasma alpha-tocopherol. Subjects
      who received pravastatin had a higher antioxidative capacity of LDL, a longer
      oxidation lag of very low density lipoprotein (VLDL) plus LDL, and a reduced
      oxidation rate of VLDL plus LDL in vitro. These data establish the
      antiatherogenic effect of lowering LDL cholesterol levels by pravastatin therapy
      in hypercholesterolemic men in a primary prevention setting and suggest that part
      of the antiatherogenic effect of pravastatin may be due to an improvement in the
      resistance of atherogenic lipoproteins to oxidation.

PMID- 7572685
TI  - Effect of pravastatin on progression and regression of coronary atherosclerosis
      and vessel wall changes in carotid and femoral arteries: a report from the
      Regression Growth Evaluation Statin Study.
AB  - Few data are available about the potential benefit of serum cholesterol reduction
      in the broad range of patients with coronary atherosclerosis and normal to
      moderately elevated serum cholesterol levels. REGRESS is a double-blind, placebo
      controlled, multicenter study to assess the effect of a 2-year treatment with the
      3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin on
      progression and regression of coronary atherosclerosis using quantitative
      coronary arteriography in 885 male patients with a total serum cholesterol value
      of 155-310 mg/dl (4-8 mmol/liter). Among symptomatic men with significant
      coronary atherosclerosis and normal to moderately raised levels of serum
      cholesterol, patients treated with pravastatin had less progression of coronary
      atherosclerosis and fewer new cardiovascular events than patients in the placebo
      group. Ultrasound examinations of carotid and femoral arteries were performed in
      255 patients. Changes in intimal-medial thickness also showed a treatment effect
      from pravastatin; however, on a per patient basis, there was no correlation with
      the treatment effect in the coronary arteries.

PMID- 7572686
TI  - Results of the primary outcome measure and clinical events from the Asymptomatic
      Carotid Artery Progression Study.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have
      proven to be more effective in reducing levels of low density lipoprotein (LDL)
      cholesterol and to be better tolerated than other lipid-lowering compounds. Most
      of the trials evaluating the effects of these new agents on progression of
      atherosclerosis have not included individuals asymptomatic for cardiovascular
      disease and who have LDL cholesterol levels at or below the limits established by
      the National Cholesterol Education Program for initiating treatment. The
      Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the
      HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis
      (as detected by B-mode ultrasonography) in 919 asymptomatic men and women, 40-79
      years of age, who had LDL cholesterol levels between the 60th and 90th
      percentiles. Participants randomized into this double-blind, placebo-controlled,
      factorially designed study received lovastatin (20-40 mg/day) or lovastatin
      placebo and warfarin (1 mg/day), or warfarin-placebo over a 3-year period. The
      progression of the mean maximum intimal-medial thickness (IMT) over 12 walls of
      both carotid arteries represented the primary outcome. Lovastatin treatment was
      associated with a reduction in progression of mean maximum IMT (p < 0.001).
      Levels of LDL cholesterol were reduced by 28% (43.5 mg/dl [11.25 mmol/liter]) in
      the lovastatin group within 6 months (p < 0.0001) and remained stable throughout
      the follow-up period, whereas these levels remained essentially unchanged in the
      lovastatin-placebo group. The difference in incidence of major cardiovascular
      events for patients in the lovastatin-placebo group was significant: 5 versus 14,
      respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572687
TI  - Unresolved issues in early trials of cholesterol lowering.
AB  - A reexamination of early intervention trials in patients with coronary artery
      disease (CAD) shows that a pessimistic view of cholesterol reduction in such
      patients is inappropriate. In observational studies, individuals with documented
      coronary artery disease and elevated cholesterol levels fare worse than
      individuals with normal or low cholesterol levels. Early trials of cholesterol
      reduction in individuals with coronary artery disease succeeded in lowering total
      cholesterol levels by only 5-15%. Nevertheless, when reviewed in meta-analysis,
      these trials demonstrated borderline effects on total mortality, statistically
      significant benefits in terms of morbidity and mortality due to cardiovascular
      disease and CAD, and no increase in mortality from noncardiovascular causes.
      Substantially greater lowering of low density lipoprotein (LDL) levels was
      achieved in early regression studies. In these studies, examples of improvement
      were noted in individual coronary artery segments. What was not appreciated
      initially was the dramatic reduction in coronary events. Older secondary
      prevention trials did not definitively address the benefits of cholesterol
      reduction in individuals whose cholesterol levels were only modestly elevated
      (total cholesterol, 160-240 mg/dl [4.14-6.21 mmol/liter], and LDL cholesterol
      levels 100-160 mg/dl [2.59-4.14 mmol/liter]). Several other issues were not
      addressed in these early studies, including the effect of declines in
      triglyceride levels, increases in high density lipoprotein (HDL) levels, and the
      effects in women and individuals aged > 60 years. Even with these limitations, a
      comparison of meta-analyses of other medical interventions--i.e. beta blockade
      and aspirin therapy--indicates that declines in coronary mortality are in the
      same range as obtained in older studies with modest cholesterol reduction--i.e.,
      20-25%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572688
TI  - Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II).
AB  - The Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries trial (PLAC
      II) was initiated in 1987 and was the first double-blind, randomized clinical
      trial with progression of early extracranial carotid atherosclerosis as an
      outcome variable. We randomized 151 coronary patients to placebo or pravastatin
      and treated them for 3 years. B-mode ultrasound quantification of carotid artery
      intimal-medial thickness (IMT) was obtained at baseline and sequentially during
      this period. The primary outcome was the change in the mean of the maximum IMT
      measurements over time. Effects on individual carotid artery segments (common,
      bifurcation, internal carotid artery) and on clinical events were also
      investigated. During follow-up, plasma concentrations of total cholesterol were
      lower in pravastatin-treated patients compared with those of placebo-treated
      patients (4.81 vs 6.08 mmol/liter [186 vs 235 mg/dl]) as were concentrations of
      low density lipoprotein (LDL) cholesterol (3.10 vs 4.29 mmol/liter [120 vs 167
      mg/dl]). Plasma concentrations of high density lipoprotein2 (HDL2) cholesterol
      were higher in pravastatin-treated patients than in placebo-treated patients
      (0.16 vs 0.14 mmol/liter [6.1 vs 5.5 mg/dl]). Active treatment resulted in a
      nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068
      mm/yr placebo to 0.059 mm/yr pravastatin) and a statistically significant 35%
      reduction in IMT progression in the common carotid (p = 0.03). Active treatment
      was also associated with a 60% reduction of nonfatal myocardial infarction plus
      death caused by coronary artery disease (p = 0.09), a 61% reduction of any fatal
      event plus any nonfatal myocardial infarction (p = 0.04), and an 80% reduction of
      fatal plus any nonfatal myocardial infarction (p = 0.03).

PMID- 7572689
TI  - Reduction in coronary events during treatment with pravastatin. PLAC I and PLAC
      II Investigators. Pravastatin Limitation of Atherosclerosis in the Coronary
      Arteries.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      statins, are more efficacious than older lipid-lowering agents and therefore may
      be more effective in reducing the incidence of coronary events. The objective of
      this prespecified analysis was to examine in coronary patients the effect of the
      lipid-lowering agent pravastatin on 3-year rates of coronary event incidence, all
      cause mortality, and nonfatal myocardial infarction (MI), and to determine
      whether any observed benefit was also evident in patients > or = 65 years of age.
      The design of this analysis was to pool the data from 2 concurrent 3-year placebo
      controlled clinical trials of pravastatin monotherapy in coronary patients
      (Pravastatin Limitation of Atherosclerosis in the Coronary Arteries [PLAC I] and
      the Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries [PLAC II]).
      This pooled database included 559 coronary patients with moderately elevated
      levels of low density lipoprotein cholesterol (between the 60th and 90th
      percentiles for age and gender in the United States). Over the 3 years of follow
      up, use of pravastatin was associated with a 55% reduction in coronary incidence
      (p = 0.014). Pravastatin was also associated with a 67% reduction in nonfatal MI
      (p = 0.006). Eleven placebo patients died over the 3 years of follow-up compared
      with 7 in the pravastatin groups (a 40% reduction). Among older patients (age >
      or = 65 years), pravastatin therapy was associated with a 79% reduction in
      coronary event incidence (95% confidence interval [CI] 33-100%) and with a 86%
      reduction in nonfatal myocardial infarction (CI, 35-100%).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7572690
TI  - Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin
      Survival Study (4S).
AB  - The Scandinavian Simvastatin Survival Study (4S) was designed to evaluate the
      effects of cholesterol reduction with simvastatin on mortality and morbidity in
      patients with coronary artery disease (CAD). A total of 4,444 patients with
      angina pectoris or previous myocardial infarction and serum cholesterol levels of
      213-310 mg/dl (5.5-8.0 mmol/liter) while treated with a lipid-lowering diet were
      randomly assigned to double-blind treatment with simvastatin or placebo. Over the
      5.4 years of median follow-up, simvastatin produced changes in total cholesterol,
      low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL)
      cholesterol of -25%, -35%, and +8%, respectively, with minimal adverse effects. A
      total of 256 patients (12%) in the placebo group died compared with 182 (8%) in
      the simvastatin group, a risk reduction of 30% (p = 0.0003) attributable to a 42%
      reduction in the risk of coronary death. Noncardiovascular causes accounted for
      49 and 46 deaths in the placebo and simvastatin groups, respectively. Major
      coronary events were experienced by 622 patients (28%) in the placebo group and
      431 patients (19%) in the simvastatin group, corresponding to a risk reduction of
      34% (p < 0.00001). This risk was also significantly reduced in subgroups
      consisting of women and patients of both sexes aged > or = 60 years. Other
      benefits of treatment included a 37% reduction (p < 0.00001) in the risk of
      undergoing myocardial revascularization procedures. Simvastatin was beneficial
      regardless of whether patients had a history of myocardial infarction or whether
      they were smokers or had hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572691
TI  - Range of serum cholesterol values in the population developing coronary artery
      disease.
AB  - Blood lipids have been established as fundamental to atherogenesis, and there is
      a better understanding of the pathogenesis of atherosclerosis and of the various
      pharmacologic agents available to counter the mechanisms involved. However, more
      optimal lipid levels must be established for treatment of both the healthy
      population and persons already with coronary artery disease (CAD). In the
      Framingham Study cohort, those with elevated serum total cholesterol (> 275
      mg/dl) had an increased risk of adverse outcomes whether healthy or with CAD.
      Compared with persons with cholesterol levels < 200 mg/dl (< 5.17 mmol/liter),
      the risk ratios for patients with elevated cholesterol levels were 3.8 for
      reinfarction, 2.6 for CAD mortality, and 1.9 for overall mortality. The
      prevalence of cholesterol levels > or = 240 mg/dl (> or = 6.21 mmol/liter) in
      persons who had sustained myocardial infarction was 35-52% in men and 66% in
      women, but 20% of myocardial infarctions occurred in people who had cholesterol
      levels < 200 mg/dl (< 5.17 mmol/liter). The average levels of serum total
      cholesterol and low density lipoprotein (LDL) cholesterol (225 mg/dl [5.82
      mmol/liter] and 150 mg/dl [3.88 mmol/liter], respectively) at which CAD events
      occurred in men were below the levels recommended for treatment according to the
      guidelines of the National Cholesterol Education Program. In women, these levels
      were only slightly above the guideline levels. The average cholesterol levels at
      which CAD events occurred were substantially higher in women and decreased with
      age. Also, a steady decline in the average cholesterol levels of patients over
      the decades reflected chiefly the aging of the cohort.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7572692
TI  - The influence of pretreatment low density lipoprotein cholesterol concentrations
      on the effect of hypocholesterolemic therapy on coronary atherosclerosis in
      angiographic trials. Harvard Atherosclerosis Reversibility Project Research
      Group.
AB  - Angiographic trials of coronary atherosclerosis treatment have demonstrated that
      lowering low density lipoprotein (LDL) cholesterol concentrations improves
      coronary artery stenosis. Most patients in previous trials have had at least
      mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility
      Project (HARP) did not find such benefit in patients with lower baseline LDL
      levels compared with previous trials. We reviewed and analyzed all cholesterol
      lowering trials that used angiographic endpoints. Unifactorial trials of
      hypocholesterolemic dietary or drug therapy demonstrated that the higher the
      baseline LDL, the greater the improvement in quantitatively determined stenosis
      in the treatment group compared with the controls (r = .83). Considering the
      change in stenosis in the treatment group alone, regression was more common in
      trials in which baseline mean LDL was > 170 mg/dl (> 4.4 mmol/liter), whereas
      progression occurred when baseline mean LDL was < 170 mg/dl (< 4.4 mmol/liter).
      HARP had the lowest baseline LDL (137 mg/dl [3.54 mmol/liter]), and showed no
      tendency for improvement in lesions. In contrast to the influence of baseline LDL
      levels, neither a low LDL level achieved on treatment nor a large percentage
      reduction in LDL was related to improvement in lesions. Sample size differences
      between HARP and the other trials are unlikely to be a major explanatory factor,
      since trials of comparable sample size to HARP, but with higher initial LDL,
      demonstrated favorable results. We conclude that coronary lesions that develop in
      the context of average LDL levels show less angiographic improvement in response
      to substantial LDL reduction than lesions in hypercholesterolemic
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572693
TI  - Lipid-lowering interventions in angiographic trials.
AB  - This analysis examines the pooled data from all 14 published randomized
      angiographic trials (with 16 treatment arms) by type of cholesterol-lowering
      intervention evaluated, and for all the trials combined. All interventions
      reduced low density lipoprotein (LDL) cholesterol levels (average reduction,
      26%), whereas the effects on high density lipoprotein (HDL) cholesterol and
      triglycerides varied by type of intervention. Meta-analyses of the angiographic
      outcomes indicated that treatment reduced the odds for disease progression by
      49%, increased the odds for no change by 33%, and increased the odds for
      regression by 219%. Cardiovascular events were reduced by 47%. Thus, lipid
      reduction is effective for modifying the angiographic outcome and for reducing
      the incidence of coronary artery disease events. All types of intervention
      (lifestyle, drugs, or surgery) had overall favorable effects on angiographic and
      clinical outcomes. There was no class effect for the statin group of drugs.
      Surgery (partial ileal bypass) had the most favorable angiographic outcome,
      possibly because of a longer duration of therapy. Trials with higher baseline LDL
      levels tended to have more favorable angiographic outcomes. Analyses of in-trial
      levels of LDL were confounded by baseline levels, and analyses of change in LDL
      levels in the treatment groups were confounded by not including zero change
      (i.e., no treatment). It is hypothesized that lowering LDL levels by 30 mg/dl
      (0.8 mmol/liter) is sufficient on average to modify the angiographic outcome,
      with modest gains from further reductions in LDL levels.

PMID- 7572694
TI  - What benefit can be derived from treating normocholesterolemic patients with
      coronary artery disease?
AB  - Controversy still remains regarding the possible clinical or arteriographic
      benefit of intensive lipid-altering therapy in patients who have coronary artery
      disease and apparently normal lipid levels. Resolution of this controversy
      appears to depend on an improved understanding of the role of variables other
      than total or low density lipoprotein cholesterol levels. A comparison of the
      "normolipidemic" subgroup of The Familial Atherosclerosis Treatment Study
      patients and The Harvard Atherosclerosis Reversibility Project patients indicates
      that low levels of high density lipoprotein cholesterol and elevated levels of
      apolipoprotein B appear to increase considerably the likelihood of benefit from
      intensive lipid-altering therapy. Other risk-related variables such as systolic
      blood pressure and lipoprotein(a) further contribute to the prediction of risk
      and possibly to the potential for treatment benefit.

PMID- 7572695
TI  - Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic
      patients. CARE Investigators.
AB  - Although elevated plasma cholesterol levels represent a well-established and
      significant risk for developing atherosclerosis, there is a wide spectrum of
      cholesterol levels in patients with coronary artery disease (CAD). Most secondary
      prevention studies have generated convincing evidence that cholesterol reduction
      in patients with high cholesterol levels is associated with improved clinical
      outcome by reducing risk of further cardiovascular events. However, other risk
      factors may play a prominent role in the pathogenesis of coronary disease in the
      majority of patients with near-normal cholesterol values. The Cholesterol and
      Recurrent Events (CARE) study was designed to address whether the pharmacologic
      reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal
      coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients
      who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2
      mmol/liter). The other inclusion criteria for this study were age 21-75 years,
      low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5
      mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0
      mmol/liter). A total of 4,159 eligible consenting patients without other study
      exclusions were then randomly assigned to receive either pravastatin 40 mg daily
      or matching placebo in addition to their individualized conventional therapy. The
      trial was designed to have a median follow-up of 5 years. Study endpoints will be
      evaluated with respect to predefined subgroups according to baseline lipid
      values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572696
TI  - One person's view of iron deficiency, development, and cognitive function.

PMID- 7572697
TI  - Accuracy of standardized equations for predicting metabolic rate in premenarcheal
      girls.
AB  - Several different equations based on height, weight, sex, and age are available
      to predict metabolic rate in children and adolescents. The purpose of this study
      was to determine which of the published standardized equations most accurately
      predicts metabolic rate in premenarcheal girls. Resting metabolic rate (RMR) was
      measured in 186 premenarcheal girls by using open-circuit indirect calorimetry
      with a ventilated hood. Measured RMR was compared with equations provided by the
      FAO/WHO/UNU, the Mayo Clinic, and Robertson and Reid for girls of the same age.
      The accuracy of each equation differed for each Tanner stage. The Mayo Clinic
      standards significantly differed from measured RMR among girls in Tanner stages 1
      and 2. The Robertson and Reid standards differed from measured RMR for girls in
      Tanner stage 1. Only the FAO/WHO/UNU equation predictions did not differ from
      measured RMR for all Tanner stages studied. These results indicate that the
      FAO/WHO/UNU equation is the best predictor of RMR in premenarcheal girls at
      different stages of development. Furthermore, because RMR measured under
      inpatient and outpatient conditions did not differ significantly, an overnight
      measurement is not necessary for a reliable determination of RMR.

PMID- 7572699
TI  - Energy balance during an 8-wk energy-restricted diet with and without exercise in
      obese women.
AB  - The effects of severe energy restriction alone (2.0 MJ/d for 4 wk and
      subsequently 3.5 MJ/d for 4 wk) or energy restriction plus moderate exercise on
      energy balance were studied in 20 healthy obese women. Subjects aged 25-50 y were
      matched on the basis of body mass index and percentage body fat and randomly
      assigned to diet alone (D) or diet and exercise (DE) for 8 wk. DE resulted in a
      significantly increased loss of fat mass compared with D (7.8 +/- 0.8 compared
      with 5.5 +/- 0.8 kg; P < 0.05). The average daily metabolic rate measured with
      doubly labeled water decreased with both treatments, with no differences between
      the treatments. Energy balance data show that the DE treatment resulted in a
      significantly greater energy deficit than the D treatment. The relative
      contribution of fat to energy expenditure during exercise was significantly
      enhanced by DE treatment whereas it did not change after D. The energy expended
      on physical activity was not changed at the end of both treatments, with no
      differences between the two groups. The unchanged energy expended on physical
      activity indicates that DE might be accompanied by partial compensation of daily
      physical activities outside the training for the energy expended during the
      training. The energy deficit due to energy restriction alone was not compensated
      by a decrease in free-living daily physical activities. Addition of moderate
      exercise to an energy-restriction program in obese women has advantages with
      respect to changes in body composition, energy expenditure, and substrate
      utilization.

PMID- 7572698
TI  - Effect of an American Heart Association diet, with or without weight loss, on
      lipids in obese middle-aged and older men.
AB  - Forty-two obese [body mass index (kg/m2): 30 +/- 5; weight: 92.9 +/- 10.1 kg] men
      aged 60 +/- 9 y were recruited to determine the effects of an American Heart
      Association (AHA) diet, with and without weight loss, on lipoprotein lipids. All
      subjects entered a 3-mo, weight-maintaining AHA diet followed by either a 9-mo
      weight-loss (AHA + WL, n = 28) or a 9-mo AHA plus weight-maintenance (AHA + WM, n
      = 14) intervention. Baseline diets were high in fat (35 +/- 6% of energy) and
      cholesterol (380 +/- 158 mg/d), and low in dietary fiber (18 +/- 5 g/d). The 3-mo
      AHA diet resulted in an 11% decrease in plasma triacylglycerol (1.83 +/- 0.15 to
      1.47 +/- 0.08 mmol/L, P < 0.05), a 16% decrease in plasma cholesterol (5.39 +/-
      0.96 to 4.56 +/- 0.91 mmol/L, P = 0.0001), a 17% decrease in high-density
      lipoprotein (HDL) cholesterol (1.09 +/- 0.23 to 0.91 +/- 0.18 mmol/L, P =
      0.0001), and a 14% decrease in low-density-lipoprotein (LDL) cholesterol (3.47 +/
      0.83 to 2.98 +/- 0.78 mmol/L, P = 0.0001) The AHA + WL group lost 9.8 +/- 4.3 kg
      (P < 0.001, n = 28) and further reduced plasma triacylglycerol by 17% (P < 0.05),
      total cholesterol by 4% (P < 0.05), LDL cholesterol by 7% (P < 0.05), and
      significantly increased HDL cholesterol by 15% (P < 0.05) when compared with
      their 3-mo AHA-intervention values. These changes were significant (P < 0.05)
      when compared with the AHA + WM group, in whom lipoprotein lipids did not
      change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572700
TI  - Use of dual-energy X-ray absorptiometry in obese individuals.
AB  - Dual-energy X-ray absorptiometry (DXA) provides precise measurements of body
      composition in humans. Because its use in obese subjects is limited by the size
      of the scanning area, we explored the possibility of estimating whole-body
      composition from DXA half-body scans. Body composition of 183 subjects with a
      wide range of body sizes [body mass index (BMI; in kg/m2) of 17.7 - 52.8] was
      assessed by DXA and hydrodensitometry. Subjects fitting in the DXA scanning area
      (group A, n = 156) were scanned once whereas subjects exceeding it (group B, n =
      27) were scanned twice, once for each side of the body. When body-composition
      results for the right and left sides were compared, only minimal differences
      between the two sides of the body were found in both groups. Least-squares
      regression analysis of whole-body composition by hydrodensitometry on DXA gave
      the following results: percent body fat, r2 = 0.89 (SEE = 4.1%); fat-free mass,
      r2 = 0.89 (SEE = 3.72 kg); and fat mass, r2 = 0.95 (SEE = 3.57 kg). Similar r2
      values and SEEs were obtained for percent body fat when only results from DXA
      half-body scans of all subjects were considered: right side, r2 = 0.90 (SEE =
      4.1%); and left side, r2 = 0.89 (SEE = 4.2%). The error in predicting body
      composition by hydrodensitometry from DXA whole- or half-body scans was not
      affected by the subject's body size and/or scanning technique. In conclusion, our
      results indicate that half-body scan values by DXA accurately predict whole-body
      composition.

PMID- 7572701
TI  - Energy metabolism in weight-stable postobese individuals.
AB  - A low metabolic rate for a given body size and body composition and a low ratio
      of fat to carbohydrate oxidation predict body weight gain. Such metabolic traits
      could also explain, in part, the propensity of previously obese (postobese)
      individuals to regain weight after dieting. We studied 11 postobese volunteers (4
      males, 7 females; aged 43 +/- 13 y, weighing 80.6 +/- 10.2 kg, with 30 +/- 7%
      body fat; x +/- SD) who lost 57 +/- 38 kg (23-139 kg) over 14 +/- 12 mo (6-48 mo)
      on various diet programs and had maintained this weight loss for > or = 2 mo (2
      72 mo; 21 +/- 27 mo). After > or = 2 d of a weight-maintenance diet on a
      metabolic ward, 24-h energy expenditure and ratio of fat to carbohydrate
      oxidation were measured in a respiratory chamber. Compared with a control group
      (n = 110) with similar physical characteristics (aged 43 +/- 14 y, weighing 79.5
      +/- 11.4 kg, with 30 +/- 12% body fat), [sequence: see text] postobese
      individuals had similar energy expenditures adjusted for fat-free mass, fat mass,
      age, and sex, but significantly higher respiratory quotients over 24 h (0.883 +/-
      0.026 compared with 0.863 +/- 0.024, P < 0.01) and during sleep, 10 h after the
      last meal (0.894 +/- 0.063 compared with 0.845 +/- 0.055). These results suggest
      that postobese individuals have low rates of fat oxidation that may explain their
      propensity to regain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572703
TI  - Body composition, body fat distribution, and resting metabolic rate in healthy
      centenarians.
AB  - Our study investigated body composition and body fat distribution in healthy
      centenarians. Body composition, body fat distribution, and resting metabolic rate
      (RMR) were studied in 40 adult subjects aged < 50 y, 35 aged subjects > 75 y, and
      15 healthy centenarians aged > 100 y. Body composition was determined by
      bioimpedance analysis, body fat distribution was calculated as waist-hip ratio
      (WHR), and RMR was calculated by using the Arciero-Poehlman formula. Healthy
      centenarians had a cognitive impairment and degree of disability greater than
      aged subjects. Despite such differences, fat-free mass (FFM) and RMR were not
      different in centenarians compared with aged subjects but were lower than in
      adult subjects. In contrast, healthy centenarians had a WHR lower than that of
      aged subjects but not different from that of the adult subjects. After the level
      of physical activity and degree of disability were adjusted for, FFM (44 +/- 2.7
      and 40 +/- 1.1 kg; P < 0.05) and RMR (6757 +/- 761 and 5891 +/- 723 kJ/24 h; P <
      0.05) were significantly higher in healthy centenarians than in aged subjects,
      respectively. Independent of age, sex, body weight, degree of disability, level
      of physical activity, and fasting plasma triiodothyronine, there was a strong
      correlation between RMR and FFM (r = 0.50, P < 0.05) in healthy centenarians. In
      conclusion, healthy centenarians had a lower FFM and higher body fat content than
      aged subjects. Level of physical activity and degree of disability seem to be the
      major determinants for explaining such differences.

PMID- 7572702
TI  - A longitudinal study of the effect of sodium and calcium intakes on regional bone
      density in postmenopausal women.
AB  - The influence of urinary sodium excretion and dietary calcium intake was examined
      in a 2-y longitudinal study of bone density in 124 women postmenopausal for > 10
      y. Analysis of bone density changes showed that urinary sodium excretion was
      negatively correlated with changes in bone density at the intertrochanteric and
      total hip sites. Multiple-regression analysis of dietary calcium intake and urine
      sodium excretion on the change in bone density showed that both dietary calcium
      and urinary sodium excretion were significant determinants of the change in bone
      mass over 2 y at the hip and ankle sites. These data suggest that an effect of
      reducing bone loss equivalent to that achieved by a daily dietary increase of 891
      mg (22 mmol) Ca can also be achieved by halving daily sodium excretion. No bone
      loss occurred at the total hip site at a calcium intake of 1768 mg/d (44 mmol/d)
      or a urine sodium excretion of 2110 mg/d (92 mmol/d). We report a significant
      effect of sodium excretion on bone loss in this population.

PMID- 7572704
TI  - Selective responses of hormones involved in carbohydrate and lipid metabolism and
      properties of erythrocyte membranes during the menstrual cycle in premenopausal
      women consuming moderate amounts of alcohol.
AB  - The effects of chronic consumption of moderate amounts of alcohol on hormones
      associated with lipid and carbohydrate metabolism, plasma concentrations of
      triacylglycerol and cholesterol, insulin receptors on erythrocyte membranes, and
      erythrocyte membrane fluidity were studied during three phases of the menstrual
      cycle in 37 premenopausal women. Subjects were given either 30 g ethanol or an
      equienergetic fruit juice for three menstrual cycles in a crossover design. Blood
      samples were analyzed during the luteal, midcycle, and follicular phases.
      Administration of alcohol induced a significant rise in plasma glucagon and
      cortisol uniformly across the entire menstrual cycle. A similar rise in plasma
      growth hormone was observed at midcycle during the period when subjects consumed
      alcohol. A marginal effect was observed on cholesterol and somatomedin C
      concentrations. Insulin binding to erythrocyte ghosts was not affected by either
      alcohol or menstrual-cycle phase. Erythrocyte membranes were more fluid during
      the follicular phase than during the luteal phase of the menstrual cycle when the
      women were consuming the alcohol. There were no perceptible interactions between
      alcohol and phases of the menstrual cycle for the indexes studied, except
      membrane fluidity.

PMID- 7572705
TI  - Effect of energy compared with carbohydrate restriction on the lipolytic response
      to epinephrine.
AB  - Fasting enhances the lipolytic sensitivity of adipose tissue to beta-adrenergic
      stimulation. The importance of carbohydrate compared with total energy
      restriction in regulating the lipolytic response to epinephrine was evaluated.
      Five normal volunteers participated in two study protocols in a randomized cross
      over design separated by a 3-wk period. In one study (total energy restriction)
      the subjects fasted for 84 h, whereas in the other (carbohydrate restriction) a
      lipid emulsion was infused for 12-15 h each day to meet resting energy
      requirements during an 84-h oral fast. Glycerol flux, an index of whole-body
      lipolysis, was measured by infusing [2H5]glycerol. Each subject was studied in
      the basal state and during a 1-h infusion of epinephrine (0.015 microgram kg(-1
      min(-1) after 84 h of total energy restriction and after 84 h of carbohydrate
      restriction (12 h after the final lipid infusion). The lipolytic response to
      epinephrine, defined as the total area between the glycerol flux curve and
      baseline during 1 h of epinephrine infusion, was similar after total energy
      restriction (241 +/- 141 mumol/kg) and carbohydrate restriction (294 +/- 58
      mumol/kg). We conclude that carbohydrate restriction, not total energy
      restriction, is responsible for the increase in lipolytic sensitivity observed
      during fasting.

PMID- 7572706
TI  - Essential fatty acid metabolism in boys with attention-deficit hyperactivity
      disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is the term used to describe
      children who are inattentive, impulsive, and hyperactive. The cause is unknown
      and is thought to be multifactorial. Based on the work of others, we hypothesized
      that some children with ADHD have altered fatty acid metabolism. The present
      study found that 53 subjects with ADHD had significantly lower concentrations of
      key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in
      red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control
      subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of
      essential fatty acid (EFA) deficiency had significantly lower plasma
      concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA
      deficiency symptoms. The data are discussed with respect to cause, but the
      precise reason for lower fatty acid concentrations in some children with ADHD is
      not clear.

PMID- 7572707
TI  - Lipoprotein concentrations in normolipidemic males consuming oleic acid-rich
      diets from two different sources: olive oil and oleic acid-rich sunflower oil.
AB  - The effects on plasma lipid concentrations of two oleic acid-rich diets, prepared
      with two different plant oils--olive oil and sunflower oil high in
      monounsaturated fatty acids (MUFAs)-- were compared with a National Cholesterol
      Education Program (NCEP) I diet. Twenty-one healthy, normolipidemic, young males
      consumed an NCEP-I diet (30% of energy as fat) during a 25-d period. Subjects
      were then assigned to two 4-wk study periods, according to a randomized,
      crossover design. Group one was placed on an olive oil-enriched diet (40% fat,
      22% MUFAs), followed by a 4-wk period of a sunflower oil-enriched diet (40% fat,
      22% MUFAs). In group two, the order of the diets was reversed. Both MUFA dietary
      periods resulted in an increase in high-density-lipoprotein (HDL) cholesterol (7%
      for the olive oil diet and 4% for the sunflower oil diet) and in apolipoprotein
      (apo) A-I (9% for both) compared with the NCEP-I diet. Low-density-lipoprotein
      (LDL) cholesterol and apo B concentrations (x +/- SEM) were lower (P < 0.05)
      during the sunflower oil diet (2.40 +/- 0.11 mmol/L, 0.85 +/- 0.04 mg/L) than
      during the olive oil diet (2.64 +/- 0.15 mmol/L, 0.93 +/- 0.05 mg/L). No
      significant differences were observed in these variables between the sunflower
      oil and NCEP-I (2.48 +/- 0.13 mmol/L, 0.89 +/- 0.04 mg/L) diets.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7572708
TI  - Effect of dietary triacylglycerol fatty acid positional distribution on plasma
      lipid classes and their fatty acid composition in preterm infants.
AB  - Seven premature infants were each fed, for 1 wk in a crossover design. The beta
      formula contained triacylglycerols resembling the stereoisomeric structure of
      human milk fat (25.4% by wt 16:0, 76.1% of which is at the sn-2 position),
      whereas in the alpha formula 87.3% of total 16:0 (25.7% by wt was at the sn-1,3
      positions. Plasma lipids and their fatty acid compositions were determined at the
      end of each 1 wk study period. Infants fed with the beta formula had higher
      percentages of palmitic acid in plasma sterol esters, triacylglycerols, and free
      fatty acids, and lower linoleic acid in triacylglycerols than with the alpha
      formula. Premature infants fed formulas with triacylglycerols 16:0 predominantly
      in the sn-2 rather than the sn-1,3 positions had alterations in their plasma
      fatty acids consistent with enhanced absorption of 16:0 from the sn-2 compared
      with the sn-1,3 positions.

PMID- 7572709
TI  - Folic acid absorption in women with a history of pregnancy with neural tube
      defect.
AB  - Folic acid absorption was compared in nonpregnant women with a history of
      pregnancy with a neural tube defect (cases)(n = 10) with that of control women (n
      = 10) with a normal pregnancy history. [2H4]folic acid was administered in an
      oral dose (400 micrograms) to fasting case and control subjects after a 30-d
      saturation protocol involving daily ingestion of two 1-mg folic acid supplements.
      Serum and red blood cell folate concentrations were not different for case and
      control subjects before or during the saturation protocol (P > 0.05). The
      percentage (x +/- SD) of the oral dose of [2H4]folic acid excreted in 24-h urine
      collections postdose was not different (P > 0.05) for case compared with control
      subjects (9.05 +/- 2.25% and 11.10 +/- 3.41%, respectively). These data suggest
      that the absorption of folic acid routinely consumed in supplements and fortified
      food products is not impaired in women with a history of a pregnancy with a
      neural tube defect. Further case-controlled studies are needed to compare the
      absorption of the predominant dietary form of the vitamin.

PMID- 7572710
TI  - Zinc absorption in infants fed iron-fortified weaning food.
AB  - The effect of fortification iron (reduced iron) on zinc absorption from a
      commercial vegetable-based weaning food was assessed in 11 9-mo-old infants. Each
      infant was fed a test meal of unfortified or iron-fortified product, labeled
      extrinsically with 1 mg 67Zn or 70Zn (as citrate), and the next day was fed the
      second product labeled with the other isotope. A complete fecal collection was
      carried out for 3-4 d, and the amount of unabsorbed isotope measured by thermal
      ionization quadrupole mass spectrometry. Apparent zinc absorption (isotope intake
      minus fecal excretion, expressed as the % of dose administered) was 31.1 +/- 8.3%
      (x +/- SD) from the iron-fortified food and 28.6%28.6 +/- 10.5% from the
      unfortified food. These values were not significantly different, thus iron
      fortification of the weaning food did not reduce zinc absorption.

PMID- 7572711
TI  - Molybdenum absorption, excretion, and retention studied with stable isotopes in
      young men at five intakes of dietary molybdenum.
AB  - A study of molybdenum absorption, excretion, and balance was conducted in four
      young men fed five amounts of dietary molybdenum, ranging from 22 to 1490
      micrograms/d, for 24 d each. The study was conducted to obtain scientific data on
      which to base a recommendation on dietary molybdenum intake for healthy young
      men. Stable isotopes of molybdenum were used as tracers. 100Mo was fed five times
      during the study and 97Mo was infused three times. 94Mo was used to quantify the
      molybdenum isotopes and total molybdenum in urine, fecal collections, and diets
      by isotope dilution. Adverse effects were not observed at any of the dietary
      intakes. Molybdenum was very efficiently absorbed, 88-93%, at all dietary
      molybdenum intakes, and adsorption was most efficient at the highest amounts of
      dietary molybdenum. The amount and percentage of molybdenum excreted in the urine
      increased as dietary molybdenum increased, suggesting that molybdenum turnover is
      slow when dietary molybdenum is low and increases as dietary molybdenum
      increases. We conclude from these results that dietary intakes between 22 and
      1500 micrograms/d by adult men are safe for > or = 24 d and that molybdenum
      retention is regulated by urinary excretion. Molybdenum is conserved at low
      intakes and excess molybdenum is rapidly excreted in the urine when intake is
      high.

PMID- 7572712
TI  - Resting energy expenditure in children with phenylketonuria.
AB  - Reports have suggested that children with phenylketonuria (PKU) weigh more
      compared with reference data. We found lower body protein and bone mineral
      density in children with PKU. These children may have a predisposition becoming
      overweight because of an alteration in body composition, which may lower resting
      energy expenditure (REE). REE was measured in 30 (15 males, 15 females) children
      with PKU (aged 9.6 +/- 2.9 y) and in 65 (23 males, 42 females) control children
      (aged 11.2 +/- 3.1 y). There was a comparable range in body fat within each group
      (control group: 11-34%; PKU group: 10-34%). The mean REE was similar between the
      male and female children with PKU (5300 +/- 757 and 4703 +/- 1024 kJ/24 h,
      respectively) and the control subjects (5306 +/- 969 and 5164 +/- 701 kJ/24 h,
      respectively). The children with PKU had an REE similar to that predicted from
      control data (males 102.1 +/- 7.8% of predicted and females 100.2 +/- 8.5% of
      predicted). This study found no evidence of a reduced REE or of increased weight
      in children with PKU.

PMID- 7572713
TI  - Effective homocysteine metabolism may protect South African blacks against
      coronary heart disease.
AB  - L-Methionine (0.1 g/kg body wt) was administered to young white [n = 18; mean (+/
      SD) age 20.0 +/- 1.0 y] and black [n = 12; mean (+/- SD) age 22.0 +/- 1.3 y]
      volunteers who had a similar lifestyle and who did not differ significantly from
      each other with respect to plasma folate or vitamin B-12 concentrations. Blacks,
      however, had significantly lower plasma pyridoxal-5'-phosphate concentrations
      compared with whites (P < 0.001). Fasting plasma homocysteine concentrations in
      blacks and whites were not significantly different. The mean (+/- SD) maximum
      increase in plasma homocysteine concentration measured after methionine loading
      was significantly lower (P < 0.01) in blacks (11.0 +/- 3.6 mumol/L) than in
      whites (18.0 +/- 6.2 mumol/L). Six weeks of vitamin supplementation (1.0 mg folic
      acid, 400 micrograms vitamin B-12, and 10 mg pyridoxine/d) reduced the mean (+/-
      SD) fasting plasma homocysteine concentration from 9.6 +/- 3.5 to 7.2 +/- 1.6
      mumol/L in whites (P < 0.05) and from 8.4 +/- 2.4 to 5.6 +/- 1.4 mumol/L in
      blacks (P < 0.01). The mean (+/- SD) maximum increase in plasma homocysteine
      concentration after methionine loading declined from 18.0 +/- 6.2 to 11.1 +/- 2.3
      mumol/L (P < 0.01) in whites, but vitamin supplementation did not have a
      significant effect on the methionine-load test in black volunteers. A significant
      race-by-time interaction shows that blacks metabolized homocysteine more
      effectively than did whites, which may partly explain their relative resistance
      against coronary heart disease despite a high prevalence of obesity,
      hypertension, and smoking.

PMID- 7572714
TI  - 1995: clinical nutrition--a medical specialty in transition.

PMID- 7572715
TI  - Herman Award Lecture, 1995: infection-induced malnutrition--from cholera to
      cytokines.
AB  - Infection-induced malnutrition, the most common form of cytokine-induced
      malnutrition, results from the actions of proinflammatory cytokines, ie, tumor
      necrosis factor (TNF) and interleukins 1,6, and 8 (IL-1, IL-6, and IL-8). During
      acute generalized infections, these cytokines initiate the acute-phase reaction.
      This reaction is quite stereotyped, and includes fever, malaise, myalgia,
      headaches, cellular hypermetabolism, and multiple endocrine and enzyme responses.
      In addition, there is heightened catabolism of muscle proteins and many amino
      acids; flux of free amino acids into the liver; hepatic synthesis of acute-phase
      plasma proteins; sequestration of iron and zinc; gluconeo-genesis; insulin
      resistance; impaired cellular uptake of fatty acids from plasma triglycerides;
      sizable losses of body nitrogen, potassium, magnesium, phosphate, and zinc;
      retention of body salt and water; heightened metabolic degradation and/or loss of
      vitamins; and an activation of the immune system. The pathogenesis of cytokine
      induced malnutrition is thus vastly different from the malnutrition caused by
      uncomplicated starvation. Cytokine-induced malnutrition can have a devastating
      effect on the immune system and its functions. Although proinflammatory cytokines
      are found in mucosal fluids, where they contribute to the pathogenesis of
      inflammatory bowel diseases, it is not known whether cytokines play a role in
      toxigenic, secretory diarrheas such as cholera, which cause huge losses of body
      water, electrolytes, and bicarbonate while exhibiting no systemic manifestations
      of an acute-phase reaction.

PMID- 7572717
TI  - National Dairy Council Award for Excellence in Medical/Dental Nutrition Education
      Lecture, 1995: medical-nutrition education--factors important for developing a
      successful program.
AB  - Currently, there are no established guidelines which define the goals, the course
      content, or the approach to developing a successful medical-nutrition education
      program. The result has been great variability in the approach to teaching
      nutrition to medical students. A common concern among medical educators is how to
      teach all of the material currently known. The obvious outcome of trying to teach
      the constantly expanding body of facts is an increasing demand and competition
      for instructional time. In turn, nutrition educators have fallen into the trap of
      vying for more time and claiming success for their program on the basis of their
      acquired number of hours of instruction rather than on the demonstrated quality
      or effectiveness of their program. The purpose of this report is to recommend a
      set of goals for nutrition training of medical students and to highlight those
      factors which appear to be most (and least) important to achieving those goals.
      It is my belief that the primary goal of educating medical students should be to
      sensitize students to the relevance of nutrition in the prevention and treatment
      of disease. A secondary goal should be to impart important information about
      nutrition. Relative to these goals, and based on previous studies and on my
      experience at the University of Alabama at Birmingham School of Medicine, I
      believe that two factors are critical to the success of any medical-nutrition
      education program: 1) demonstrated relevance of the course material to the
      practice of medicine, and 2) positive role modeling.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7572716
TI  - McCollum Award Lecture, 1995: diet, lifestyle, and weight maintenance.

PMID- 7572718
TI  - Nutritional attributes of dietary flaxseed oil.

PMID- 7572719
TI  - Vitamin A and malaria.

PMID- 7572720
TI  - Dietary trans fatty acids and lipoprotein cholesterol.

PMID- 7572722
TI  - International tables of glycemic index.
AB  - The glycemic index (GI) is a ranking of foods based on their glycemic effect
      compared with a standard food. It has been used to classify carbohydrate foods
      for various applications, including diabetes, sports, and appetite research. The
      purpose of these tables is to bring together all of the published data on the GIs
      of individual foods for the convenience of users. In total, there are almost 600
      separate entries, including values for most common Western foods, many indigenous
      foods, and pure sugar solutions. The tables show the GI according to both the
      glucose and white bread (the original reference food) standard, the type and
      number of subjects tested, and the source of the data. For many foods there were
      two or more published values, so the mean +/- SEM was calculated and is shown
      together with the original data. These tables reduce unnecessary repetition in
      the testing of individual foods and facilitate wider application of the GI
      approach.

PMID- 7572721
TI  - Intake of carbohydrate and its components--international comparisons, trends over
      time, and effects of changing to low-fat diets.
AB  - Carbohydrate constitutes the major source of dietary energy for all peoples of
      the world. However, it has been difficult to make accurate determinations of
      intakes of carbohydrate and its constituents because of lack of individual
      assessments in which carbohydrate components are included. For many countries,
      only food balance information is available and values for total carbohydrate are
      often derived by difference. Available information indicates that carbohydrate
      consumption decreased in many industrialized nations as prosperity led to an
      increased consumption of fat. Fat intakes have fallen over the past two decades
      and carbohydrate intakes have increased, but still do not approach the 60
      70%contribution of carbohydrate to total energy in developing countries. A
      negative image for carbohydrate has led to a reluctance to accept it as a
      legitimate dietary component, particularly in North America. New evidence of the
      beneficial effects of starch in the diet indicates that increased consumption of
      carbohydrate, especially in the form of starch, should be promoted in Western
      countries.

PMID- 7572723
TI  - Effect of yogurt on symptoms and kinetics of hydrogen production in lactose
      malabsorbing children.
AB  - Lactase-deficient adults demonstrate improved lactose absorption and fewer
      symptoms when consuming yogurt than when consuming milk containing equivalent
      amounts of lactose. To examine this effect and its mechanisms in children, we
      compared symptoms and hydrogen production as an index of lactose malabsorption
      after typical servings of milk, pasteurized yogurt, and yogurt containing active
      live culture in 14 lactose-malabsorbing children (mean age 9.5 y). Symptoms and
      interval breath-hydrogen concentrations were recorded for 8 h after ingestion of
      12 g lactose served as milk and yogurts. Lactose-malabsorbing children
      experienced significantly fewer symptoms after consuming yogurt containing active
      cultures than after consuming milk (P < 0.005). Pasteurized yogurt showed an
      intermediate effect. Lactose from yogurt was not better absorbed than was lactose
      from milk, as indicated by similar areas under the hydrogen curve; however,
      yogurt was associated with a delayed time to rise and lower rate of rise of the
      hydrogen curve. The rate of hydrogen rise correlated with the degree of symptoms.
      In children, mechanisms other than enhanced lactose absorption from yogurt may
      lead to changes in the kinetics of hydrogen production, which in turn are
      associated with improved tolerance.

PMID- 7572724
TI  - Immunologic memory is established in nursling rats immunized with tetanus toxoid,
      but is not affected by concurrent supplementation with vitamin A.
AB  - Experiments were conducted to determine whether nursling rats immunized with
      tetanus toxoid (TT) are able to produce a specific antibody response and whether
      oral treatment with retinyl palmitate, concurrent with immunization, affects the
      magnitude of the anti-TT response. When rats aged 8-15 d and nursed by vitamin A
      sufficient dams were immunized with TT, no primary anti-TT immunoglobulin (Ig) M
      or IgG response was detected. However, nursling rats formed immunologic memory to
      TT because, when they were reimmunized at 40 d of age, their secondary anti-TT
      IgG response exceeded the primary response of 40-d-old vitamin A-sufficient rats
      (P < 0.02). Provision of retinyl palmitate (equal to 37.5 or 150 micrograms
      retinol equivalents) by mouth with early primary immunization did not change the
      magnitude of the secondary anti-TT IgG response. However, the age of nursling
      rats at first immunization significantly affected the magnitude of their
      secondary anti-TT IgG response, because rats first immunized at 15 d of age and
      reimmunized at 40 d of age produced a secondary response that was nearly fivefold
      greater than that of rats immunized at 8 and 40 d of age. In conclusion, nursling
      rats immunized with TT formed immunologic memory, which was affected
      significantly by the timing of the primary immunization. However, the
      administration of retinyl palmitate concurrent with early primary immunization
      did not significantly affect the development of memory to TT.

PMID- 7572725
TI  - Vitamin B-12 deficiency and malabsorption are highly prevalent in rural Mexican
      communities.
AB  - Vitamin B-12 status of rural Mexicans was evaluated in two studies, 6 y apart. In
      the first, a single blood sample was collected from children and adults,
      including pregnant and lactating women. Prevalence of deficient plasma vitamin B
      12 values ranged from 19% to 41% among groups, but plasma folate status was
      normal in all individuals. Breast milk vitamin B-12 concentration was low in 62%
      of samples. The second study was conducted in 219 children aged 18-36 mo in five
      communities, whose prevalence of deficient and low plasma vitamin B-12
      concentrations, respectively, was 8% and 33% on entry, 3% and 22% 6 mo later, and
      7% and 29% 12 mo later. Prevalence of low holotranscobalamin II concentrations,
      indicating malabsorption of the vitamin, averaged 18-40% across the three same
      periods. Both vitamin B-12 status indicators differed significantly between
      communities. The widespread vitamin B-12 deficiency was probably caused by
      malabsorption, perhaps exacerbated by low dietary intake and, for young children,
      maternal depletion of the vitamin.

PMID- 7572726
TI  - Prevalence of goiter in schoolchildren in Kashmir Valley, India.

PMID- 7572727
TI  - Palmolein, olive oil, and serum lipids.

PMID- 7572729
TI  - Anthelmintic therapy and iron supplementation of pregnant women.

PMID- 7572728
TI  - Low activity of branched-chain alpha-keto acid dehydrogenase complex in human
      liver.

PMID- 7572730
TI  - Recognition of nutrition expertise is more important than certification.

PMID- 7572731
TI  - Alfalfa, vitamin E, and autoimmune disorders.

PMID- 7572732
TI  - Alfalfa pills and autoimmune diseases.

PMID- 7572733
TI  - Glutamine--a conditionally essential amino acid in cirrhosis?

PMID- 7572734
TI  - Energy expenditure determined by the doubly labeled water method in Bolivian
      Aymara living in a high altitude agropastoral community.
AB  - Using the doubly labeled water method (DLW), we determined total energy
      expenditure (TEE) under free-living conditions in 23 rural Bolivian Aymara (males
      and females aged 4-65), natives of a small, high-altitude (4000-4100 m), rural
      agropastoral community in the Andes mountains. In the adults (18-65 y of age),
      mean TEEs for males and females were 11.1 +/- 1.8 MJ/24 h (range: 9.3-14.1) and
      9.8 +/- 0.9 MJ/24 h (8.8-11.3). Non basal energy expenditure expressed as TEE
      relative to basal energy expenditure (TEE:RMR) and as the difference between TEE
      and RMR per unit of weight [(TEE-RMR)/wt] showed no significant sex differences.
      TEE:RMR in the adults (2.00 +/- 0.21) was significantly greater (P < 0.05) than
      that of adolescents and children (1.67 +/- 0.25), but the mean (TEE-RMR)/wt
      values were similar in children, adolescents, and adults. Significantly high
      RMR:FFM values in children and adolescents, reflecting a curvilinear relation of
      RMR and FFM, have enlarged the differences in TEE:RMR by age groups. When
      compared with other DLW studies for free-living nonobese adults, the RMR of adult
      Aymara subjects normalized by the ratio method (RMR:FFM) and by the regression
      based method (RMR adjusted with FFM as the covariate) was not significantly
      different from that observed in subjects living in low altitudes. As compared to
      FAO/WHO/UNU (1985) recommendations, activity levels were classified as heavy for
      the adult females and moderate-heavy for the adult males. Energy requirements for
      maintaining everyday tasks in the Andean people are much higher than expected
      from the previous studies on food consumption.

PMID- 7572735
TI  - Ad libitum food intake on a "cafeteria diet" in Native American women: relations
      with body composition and 24-h energy expenditure.
AB  - Epidemiologic studies consistently report associations between obesity and
      dietary fat but not total energy intake. We measured ad libitum food intake in a
      laboratory setting and evaluated its relation to body weight and composition,
      energy expenditure, and macronutrient utilization in 28 women of Pima-Papago
      heritage (aged 27 +/- 7 y, 85.3 +/- 19.0 kg, 44 +/- 6% body fat; means +/- SD).
      All women were studied during the follicular phase of the menstrual cycle. After
      a 4-d weight-maintenance period, the volunteers selected their food for 5 d from
      computerized vending machines offering a variety of familiar and preferred foods,
      ie, a "cafeteria diet". Twenty-four-hour energy expenditure and substrate
      oxidation were measured in a respiratory chamber on the 4th d o weight
      maintenance and the 5th d of ad libitum intake. Average ad libitum intake was
      13,732 +/- 4238 kJ/d (11 +/- 1% protein, 40 +/- 1% fat, 49 +/- 4% carbohydrate),
      ie, moderate overeating by 27 +/- 37% above weight maintenance requirements
      (range: -27% to 124%). Percent body fat correlated with daily energy intake (r =
      0.53, P < 0.01), the degree of overeating (r = 0.41, P < 0.05), and the selection
      of a diet higher in fat and lower in carbohydrate (r = 0.70 and r = -0.63,
      respectively, P < 0.001). Excess carbohydrate intake caused an increase in
      carbohydrate oxidation (r = 0.51, P < 0.01), whereas excess fat intake resulted
      in a decrease in fat oxidation (r = -0.53, P < 0.01) and thus a positive fat
      balance of 85 +/- 65 g/d. The positive relations among degrees of obesity,
      dietary fat intake and overeating, and the fact that dietary fat does not induce
      fat oxidation, support the hypothesis that dietary fat promotes obesity in women.

PMID- 7572736
TI  - Visceral adiposity is associated with increased lipid oxidation in obese,
      postmenopausal women.
AB  - Lipolysis is increased in upper-body obese individuals but it is unclear whether
      body fat distribution is associated with differences in resting metabolic rate
      (RMR) and/or substrate oxidation in older women. This study determined whether
      RMR and lipid oxidation are higher in postmenopausal women with visceral obesity.
      A single-slice computed tomography scan was taken midway between L4 and L5 in 29
      women aged 52-72 y with a fat mass of 29.2-68.8 kg. RMR and lipid oxidation rates
      were measured by using indirect calorimetry. RMR was related to waist
      circumference (r = 0.45, P < 0.05), but not to waist-hip ratio (WHR; r = 0.23) or
      intraabdominal fat area (r = 0.26). However, there was a strong, positive
      relation between lipid oxidation and intraabdominal fat area (r = 0.57, P <
      0.01), waist circumference (r = 0.54, P < 0.01), and WHR (r = 0.42, P < 0.05).
      These correlations remained significant after statistical adjustment for total
      fat and fat-free mass. These results suggest that in postmenopausal women higher
      amounts of intraabdominal fat are associated with an enhanced rate of lipid
      oxidation independent of total adiposity, but not with alterations in RMR.

PMID- 7572737
TI  - Age-related impairments in the regulation of food intake.
AB  - Low food intake in elderly individuals increases the risk for many nutrition
      related acute or chronic illnesses. It is not known whether aging is associated
      with changes in hunger and satiety, or whether elderly individuals can regulate
      energy intake in response to manipulations of the energy or nutrient content of
      foods. Therefore, this study investigated short-term energy regulation in healthy
      elderly (n = 16; aged 60-84 y) and young (n = 16; aged 18-35 y) men. Participants
      were given yogurt preloads that varied in energy and macronutrient content (low
      fat, low-energy, 962 kJ; high-fat, high-energy, 2134 kJ; high-carbohydrate, high
      energy 2134 kJ), or no yogurt, followed by a self-selected lunch (presented 30
      min after subjects began to consume the yogurt). Energy intake, the percentage of
      macronutrients consumed in the meals, and subjective sensations of hunger and
      satiety were analyzed. The elderly men consumed significantly less energy than
      the young men in the baseline (no yogurt) condition. Lower intake was concordant
      with subjective sensations of satiety; visual analog data indicated that the
      older men were less hungry and more full at the start of lunch. Compensation for
      energy in the preloads was less precise in the elderly than in the young men, in
      that elderly men consistently overate at the self-selected lunch. Young men
      consumed +/- 10% total energy (lunch + yogurt) in the yogurt preload conditions
      compared with their baseline intake; elderly men overate between 10% and 30% in
      relation to their baseline intake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7572738
TI  - Vitamin B-6 adequacy in neonatal nutrition: associations with preterm delivery,
      type of feeding, and vitamin B-6 supplementation.
AB  - Concerns about vitamin B-6 adequacy in neonatal nutrition relate to critical
      functions of the vitamin in development. Vitamin B-6 status was assessed in six
      groups of neonates: two groups each of breast-fed term and preterm infants whose
      mothers were supplemented with 2 or 27 mg pyridoxine-hydrochloride (PN-HCl); a
      subgroup of term infants (2-mg maternal group) supplemented with 0.4 mg PN-HCl/d;
      and a formula-fed preterm group. During the 28-d experimental period, weekly
      assessments showed lower concentrations of total vitamin B-6 and percentages of
      pyridoxal in milk from mothers of preterm infants than in milk from mothers of
      term infants, even when maternal PN-HCl supplementation was 27 mg/d. The vitamin
      B-6 concentration of milk and estimated intakes of the vitamin by breast-fed
      infants paralleled maternal supplements (ie, 2 and 27 mg). Plasma and erythrocyte
      measurements of infants correlated with their vitamin B-6 intakes; values were
      highest for infants given vitamin B-6 supplements and those that wee formula-fed.
      Vitamin B-6 adequacy was questionable for unsupplemented breast-fed infants of
      mothers in the 2-mg supplemented groups.

PMID- 7572739
TI  - Erythrocyte and plasma cholesterol ester long-chain polyunsaturated fatty acids
      of low-birth-weight babies fed preterm formula with and without ribonucleotides:
      comparison with human milk.
AB  - We investigated whether a regular formula for premature infants (pre)
      supplemented with ribonucleotides (pre+RN) raises erythrocyte and plasma
      cholesterol ester (CE) long-chain polyunsaturated fatty acids (LCPUFAs) of low
      birth-weight babies (< or = 2.50 kg) compared with their breast-fed counterparts.
      From days 11 to 42, 31 babies received the pre formula and 37 received pre+RN.
      Eleven breast-fed babies served as a reference group. Erythrocytes and CE fatty
      acids were determined on days 11, 21, and 42. There were no differences in the
      courses of erythrocytes and CE fatty acids between pre formula-fed and pre+RN-fed
      babies. On day 42, formula-fed babies had lower erythrocytes and CE n-3 and n-6
      LCPUFAs compared with breast-fed babies. Subdivision into gestational age- and
      body weight-matched subgroups gave similar results. RN supplementation does not
      augment the erythrocyte and CE LCPUFA status of formula-fed babies.

PMID- 7572740
TI  - Effect on plasma lipids of interesterifying a mix of edible oils.
AB  - The aim was to establish whether interesterification of oils, an alternative to
      the use of trans fatty acids in margarine manufacture, adversely affects plasma
      lipids. Twenty-seven hypercholesterolemic men participated in a double-blind,
      crossover trial of three margarines: 1) high-linoleic acid, moderate trans fatty
      acids; 2) high-palm oil blend (predominantly lauric, myristic, palmitic, oleic,
      and linoleic acids); and 3) an interesterified form of the high-palm oil
      margarine. Both high-palm oil margarines led to similar low-density-lipoprotein
      (LDL) cholesterol concentrations (4.43 +/- 0.94 and 4.54 +/- 0.88 mmol/L,
      respectively), which were significantly higher than the LDL concentrations after
      the high-linoleic acid margarine (4.02 +/- 0.85 mmol/L, P < 0.001).
      Interesterification transferred substantial proportions of palmitic acid into the
      sn-2 position of glycerides and unsaturated fatty acids into the sn-1,3
      positions, and this was reflected in plasma chylomicrons. This study shows that
      interesterification of oils used to harden margarines does not raise plasma
      cholesterol more than does the margarine's constituent fatty acids.

PMID- 7572741
TI  - Biomarkers of habitual fish intake in adipose tissue.
AB  - The association between habitual fish and marine n-3 polyunsaturated fatty acid
      (PUFA) intake, and the fatty acid composition of subcutaneous fat was studied in
      24 healthy young volunteers. Habitual dietary intakes were estimated from three 7
      d weighted food records made at months 0, 5, and 8 of the 8-mo study period. The
      adipose tissue fatty acid composition of each individual was determined by gas
      chromatography as the mean of two gluteal biopsies, obtained in the first and the
      last month of the study. The daily consumption of fish and of marine n-3 PUFAs in
      absolute terms (g/d) was significantly associated with adipose tissue
      docosahexaenoic acid content (DHA; r = 0.55 and 0.58, respectively, P < 0.001),
      but not with eicosapentaenoic and docosapentaenoic acid contents. Our study
      indicates that the adipose tissue DHA content is the biomarker of choice for the
      assessment of long-term habitual dietary intakes of fish and marine n-3 PUFAs.

PMID- 7572742
TI  - Relations among arginine, citrulline, ornithine, and leucine kinetics in adult
      burn patients.
AB  - Plasma fluxes of arginine, citrulline, and leucine, and the rate of conversion of
      labeled citrulline to arginine (Qcit-->arg) were determined in nine severely
      burned patients (mean: 56% body surface burn area, mean 10 d postinjury) while
      they received total parenteral nutrition (TPN) including an L-amino acid mixture
      that supplied a generous amount of nitrogen (mean: 0.39 +/- 0.02 g.kg-1.d-1).
      Plasma fluxes were also studied in these patients during a basal state (low-dose
      intravenous glucose) by using a primed, 4-h constant intravenous tracer-infusion
      protocol. Stable-nuclide labeled tracers were L-[15N-15N
      guanidino,5,5,2H2]arginine; L-[13C-ureido]citrulline; L-[1-13C]leucine; and
      NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to
      determine isotopic abundance of arginine, citrulline, ornithine, and alpha
      ketoisocaproate (KIC; for leucine) in plasma and 13CO2 in breath. Leucine
      kinetics (flux and disappearance into protein synthesis) confirmed the
      anticipated higher protein turnover in these burn patients compared with healthy
      control subjects. The plasma arginine fluxes were correspondingly higher in burn
      patients than in healthy control subjects. However, the citrulline flux and rate
      of conversion of citrulline to arginine were not higher than values obtained in
      our laboratories in healthy adult subjects. We hypothesize that the higher rates
      of arginine loss from the body after burn injury would need to be balanced by an
      appropriate exogenous intake of preformed arginine to maintain protein
      homeostasis and promote recovery from this catabolic condition.

PMID- 7572743
TI  - Cereal feeding and its impact on the nitrogen economy of the infant.
AB  - To quantify the effect of rice cereal on nitrogen balance and fecal nitrogen
      excretion, and the contribution of endogenous nitrogen sources to fecal nitrogen
      output, nine infants aged 3-5 mo received [15N]glycine in all feedings. Samples
      of urine and feces were obtained daily and analyzed for nitrogen and 15N. On days
      1-7 the infants received only formula, and a complete urine and fecal collection
      was made on days 6-7. From days 8 to 12 the formula was supplemented with rice
      cereal (133.3 g/L, or 4 g/30 mL formula) and a second complete urine and fecal
      collection was made on days 11-12. Cereal did not alter fecal nitrogen output or
      the calculated contribution (45%) of endogenous nitrogen to fecal nitrogen.
      Cereal did increase nitrogen retention and lower the urinary excretion of the 15N
      dose (24% of dose). The calculated true digestibility of the rice cereal protein
      was > 95%. Our results indicate that infants aged 4 mo, in contrast with younger
      infants, are able to digest and absorb cereal. The addition of cereal to the diet
      does not lead to increased fecal protein losses.

PMID- 7572744
TI  - Effect of colonic fermentation on respiratory gas exchanges measured in the
      postabsorptive state.
AB  - To assess the effect of colonic fermentation on respiratory gas exchanges, six
      methane-nonproducing healthy volunteers ingested in the postabsorptive state 1 wk
      apart either 90 mL lactulose syrup containing 60 g lactulose, 4 g lactose, and 7
      g galactose or the same solution but without lactulose (control solution). Six
      patients with short bowel and remnant colon (SBS) also ingested 90 mL lactulose
      syrup. Carbon dioxide production (VCO2), oxygen consumption (VO2), respiratory
      quotient (RQ), and hydrogen excreted in breath were measured basally and for 4 h
      after the ingestion of solutions. In healthy volunteers within 4 h after
      ingestion of the control solution, VCO2 and the RQ decreased whereas VO2 remained
      unchanged. In contrast, in healthy volunteers and patients with SBS, VCO2 and the
      RQ increased after lactulose ingestion, whereas VO2 did not change. The increase
      in VCO2 appeared to be accounted for mainly by bacterial production of carbon
      dioxide and was significantly related to breath-hydrogen concentration (r = 0.56,
      P < 0.02 for healthy subjects; r = 0.59, P < 0.01 for SBS subjects). A breath
      hydrogen test should be performed in conjunction with indirect calorimetry to
      determine whether colonic fermentation is taking place and, if so, to correct
      appropriately the VCO2 value in calorimetric equations.

PMID- 7572745
TI  - Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed
      rest.
AB  - Vitamin B-6 metabolism in 10 volunteers during 21 d of total fasting was compared
      with results from 10 men consuming a diet low only in vitamin B-6 (1.76 mumol/d)
      and with men consuming a normal diet during bed rest. At the end of the fast mean
      plasma concentrations of vitamin B-6 metabolites and urinary excretion of 4
      pyridoxic acid tended to be higher in the fasting subjects than in the low
      vitamin B-6 group. The fasting subjects lost approximately 10% of their total
      vitamin B-6 pool and approximately 13% of their body weight. The low-vitamin B-6
      group lost only approximately 4% of their vitamin B-6 pool. Compared with
      baseline, urinary excretion of pyridoxic acid was significantly increased during
      17 wk of bed rest. There was no increase in pyridoxic acid excretion during a
      second 15-d bed rest study. These data suggest the possibility of complex
      interactions between diet and muscle metabolism that may influence indexes that
      are frequently used to assess vitamin B-6 status.

PMID- 7572746
TI  - Manganese absorption in humans: the effect of phytic acid and ascorbic acid in
      soy formula.
AB  - The absorption of manganese from soy formula was studied in adult volunteers by
      extrinsic labeling of test meals with 54Mn, followed by whole-body retention
      measurements for approximately 30 d after intake. Eight subjects participated
      twice in each of the two studies, acting as his or her own control. Soy formula
      containing the native content of phytic acid was compared with a similar
      dephytinized formula: geometric mean manganese absorption increased 2.3-fold from
      0.7% (range: 0.2-1.1%) to 1.6% (range: 1.0-7.2%) (P < 0.01) with the dephytinized
      formula. In addition, the effect of the ascorbic acid content of the phytic acid
      containing formula was investigated. Manganese absorption was not influenced by
      an increase in the ascorbic acid from 625 mumol/L (110 mg/L) to 1250 mumol/L (220
      mg/L): the geometric mean manganese absorption was 0.6% (range: 0.3-1.0%) and
      0.6% (range: 0.3-1.1%), respectively. In conclusion, fractional manganese
      absorption was approximately doubled by the dephytinization of soy formula but
      was not influenced by an increase in the ascorbic acid content of a soy formula
      containing the native amount of phytic acid.

PMID- 7572748
TI  - Mechanisms of increase in plasma triacylglycerol concentrations as a result of
      high carbohydrate intakes in patients with non-insulin-dependent diabetes
      mellitus.
AB  - To determine the mechanisms of increase in plasma triacylglycerol concentrations
      after high dietary intakes of carbohydrates, 10 men with non-insulin-dependent
      diabetes mellitus (NIDDM) were fed an isoenergetic high-carbohydrate diet (55% of
      energy as carbohydrate and 30% as fat) and a high-monounsaturated-fat diet (45%
      of energy as fat and 40% as carbohydrates) for 6 wk in a randomized, crossover
      manner. The high-carbohydrate diet raised fasting plasma triacylglycerol
      concentrations by 26% (P = 0.007) but did not affect postheparin lipoprotein
      lipase (P = 0.2) or hepatic lipase activities (P = 0.9). The oral-fat-tolerance
      test labeled with retinyl palmitate also revealed no differences in postprandial
      plasma triacylglycerol (P = 0.37) or retinyl palmitate clearances (P = 0.34)
      between the two diets. We conclude that the increase in plasma triacylglycerol
      concentrations with high-carbohydrate diets in men with NIDDM is not due to
      reduced lipolysis or diminished postprandial clearance of triacylglycerol-rich
      lipoproteins but is primarily due to increased hepatic secretion of very-low
      density-lipoprotein triacylglycerols.

PMID- 7572747
TI  - Changes in plasma triacylglycerol concentrations among free-living hyperlipidemic
      men adopting different carbohydrate intakes over 2 y: the Dietary Alternatives
      Study.
AB  - We reported previously that low-fat, high-carbohydrate diets containing < 26% of
      energy as fat and > 57% of energy as carbohydrate induce hypertriacylglycerolemia
      (hypertriglyceridemia) in hypercholesterolemic but not in combined hyperlipidemic
      (CHL) subjects. Because subjects may not consistently adhere to an assigned diet
      long term, we examined the extent to which plasma triacylglycerols
      (triglycerides) increase at four consistently reported carbohydrate intakes at
      intervals of up to 2 y. Three hundred seventy-two subjects reported consistent
      carbohydrate intakes of < 45%, 45-51.9%, 52-59.9%, or > or = 60% of energy on
      food records for 3, 12, and 24 mo. Among hypercholesterolemic subjects reporting
      a carbohydrate intake > or = 60% of energy, triacylglycerols increased by 0.25,
      0.18, and 0.27 mmol/L (22, 16, and 24 mg/dL) over baseline at 3, 12, and 24 mo,
      respectively (P < 0.01 in each instance), and 0.32 mmol/L (28 mg/dL) above the
      group with a carbohydrate intake 52-59.9% of energy (P < 0.05) after 3 mo. No
      statistically significant effects were observed among CHL subjects, but compared
      with baseline, triacylglycerols decreased during the first 3 mo (-0.29 to -0.04
      mmol/L, or -26 to -4 mg/dL), were unchanged over 12 mo, and were increased after
      24 mo in three of four carbohydrate intake strata (0.27-0.36 mmol/L, or 24-32
      mg/dL). These data confirm our previous observation that a moderately but not
      extremely low-fat, high-carbohydrate diet can be used long-term without
      deleterious effects on plasma triacylglycerols in the management of
      hypercholesterolemia, whereas CHL is unaffected by the amount of carbohydrate
      ingested.

PMID- 7572749
TI  - A pilot study of concomitant protracted venous infusion 5-fluorouracil and
      hyperfractionated radiotherapy in rectal tumors.
AB  - It has recently been shown that postoperative radiotherapy combined with 5
      fluorouracil (5FU) resulted in an increase of survival and local control in
      patients with rectal cancer. However, hematological and intestinal toxicity were
      also increased. Experimental and clinical studies showed an increased radiation
      effect with an acceptable toxicity by delivering 5FU via a continuous intravenous
      infusion. From July 1988, 38 patients radically operated on for stages B2-C
      rectal cancer were irradiated in our hospital with 3 fractions per day of 100 cGY
      to a total dose of 5,600 cGY. Of these 38 patients, 13 underwent postoperative
      radiotherapy alone, and 25 received postoperative radiotherapy combined with
      concomitant protracted infusion of 5FU at doses of 250 and 300 mg/m2 per day. In
      addition, 14 patients with inoperable, locally advanced tumors or postoperative
      recurrences, were treated with the same combination schedule of 5FU and
      radiotherapy to a total radiation dose of 6,500 cGy. After a median follow-up of
      43 months, the actuarial 3-year overall and disease-free survival rates in the
      postoperative group of patients were 68% and 68%, respectively, in the combined
      modality group, as compared to 51% and 36%, respectively, in the radiation alone
      group. Patients with inoperable tumors exhibited 3-year overall and disease-free
      survival rates of 24% and 32%, respectively. The main toxicity was rectal
      tenesmus, diarrhea, dysuria, and, less frequently, leukopenia. These symptoms
      were responsible for a treatment delay of more than 5 days in 2 of 6 and in 7 of
      33 patients who received 5FU doses of 300 and 250 mg/m2 per day, respectively, as
      compared to 2 of 13 patients treated with radiotherapy alone.

PMID- 7572750
TI  - Radiotherapy alone compared with radiotherapy and chemotherapy in patients with
      squamous cell carcinoma of the esophagus.
AB  - PURPOSE: The purpose of this study is to determine whether primary treatment with
      both radiotherapy and chemotherapy is superior to radiotherapy alone in patients
      with squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: From January
      1980 to December 1988, 77 patients from two Veterans Affairs hospitals with
      clinically staged nonmetastatic squamous cell carcinoma of the esophagus received
      either radiotherapy alone (RT group) or concomitant radiotherapy and chemotherapy
      (RT + CT group) with curative intent. Each group originated at a different
      hospital, but all patients were irradiated in the same radiotherapy department.
      Chemotherapy consisted of cisplatin and 5-fluorouracil. Forty-two patients
      received RT alone, and 35 received RT + CT. Locoregional control, disease-free
      survival, and overall survival rates were compared. RESULTS: Locoregional
      control, disease-free survival, and overall survival rates were significantly
      higher in the RT + CT group when compared to RT group, 26% vs 5%, 20%, vs 2%, and
      29% vs 7%, respectively, at 2 years (P = .01, 0.02 and 0.02, respectively). The
      median survival was 14 months for the RT + CT group and 7.5 months for the RT
      group. There was no difference in the incidence of distant metastases except for
      bone metastases. No one in the RT + CT group developed bone metastases compared
      to nine patients in the RT group (P = .01). CONCLUSION: This retrospective
      analysis shows improved locoregional control, disease-free survival, and survival
      when chemotherapy consisting of cisplatin and 5-FU is given in addition to
      radiation for patients with squamous cell carcinoma of the esophagus. Bony
      metastases were absent in those who received chemotherapy.

PMID- 7572751
TI  - Continuous infusion etoposide/carboplatin for treatment of refractory acute
      leukemia.
AB  - Etoposide (125 mg/m2/d) and carboplatin (200 mg/m2/d) were administered by
      continuous 5-day intravenous infusion to 10 patients with relapsed or refractory
      acute leukemia (7 ANLL, 1 ALL, 2 blast crisis of CGL). No complete or partial
      response was observed despite dose-limiting toxicity characterized by severe
      diarrhea in four patients and neutropenic colitis in two additional cases. We
      cannot recommend the present schedule of drug administration for the treatment of
      acute leukemia.

PMID- 7572752
TI  - Phase II trial of 5-fluorouracil, folinic acid, and N,N1,N11
      triethylenethiophosphoramide (thiotepa) in patients with advanced breast cancer.
AB  - A total of 35 women with advanced, metastatic breast cancer were treated with
      combination chemotherapy consisting of folinic acid 500 mg/m2 over 2 hours
      administered with 600 mg/m2 of 5FU at the midpoint of the folinic acid infusion
      weekly for 6 weeks, plus 60 mg/m2 of thiotepa on day 1 and day 28. The cycle was
      repeated every 8 weeks. Patients were evaluated for toxicity weekly. Response was
      evaluated at the end of each 8-week cycle. The median age was 55 years (range: 34
      67). Prior to this study 30 patients had received chemotherapy; 13 had 1 regimen;
      17 had 2 or more regimens; 8 had 5FU treatment. The overall response rate was 40%
      (1 complete and 13 partial); median duration of response was 4 months. Four of 8
      patients with prior 5FU responded. Hematologic toxicity was significant; nadir
      WBC count: < 1,000/mm3 (10 patients); 1,000-1,999/mm (13 patients); nadir
      platelet count: < 20,000/mm3 (8 patients): 20,000-49,000/mm3 (8 patients); 50,000
      99,000/mm3 (10 patients). We conclude that the combination of thiotepa, 5FU, and
      leucovorin had significant myelotoxicity and do not recommend its routine use in
      the treatment of metastatic breast cancer.

PMID- 7572753
TI  - Control of advanced chemodectomas of the head and neck with irradiation.
AB  - Long-term follow-up of 15 patients treated with definitive radiotherapy for
      advanced glomus tumors of the head and neck is presented. Disease was locally
      controlled in all patients. A prescribed dose above 4,500 cGY did not improve
      treatment results. Radiation therapy remains the treatment of choice for advanced
      glomus tumors.

PMID- 7572754
TI  - Phase II trial of weekly i.v. vinorelbine as a single agent in first-line
      advanced breast cancer chemotherapy. The Latin-American experience.
AB  - This study investigated the therapeutic effect of single-agent i.v. weekly
      Navelbine (vinorelbine), a semisynthetic vinca alkaloid, in women who had
      received no prior treatment for locally advanced or metastatic breast cancer. Of
      68 patients entered into the study, 63 were adequate inclusions, assessable for
      toxicity and response by WHO criteria; the 5 patients who were not evaluated were
      excluded from analysis because they were found not to meet the eligibility
      criteria of the study. Navelbine was given as a weekly 30 mg/m2 short i.v. (20
      minutes) infusion; treatment was continued until disease progression. The overall
      response rate was 44% (complete response 8%, partial response 36%). The response
      rate according to target was lymph nodes, 62.9%; liver, 50.0%; lung, 50.0%; skin,
      37.5%; and primary tumor, 30.8%. The median duration of response was 17.9 weeks
      (range: 7-52 weeks). The median time to treatment failure was 12.9 weeks, and the
      median survival was 50.3 weeks. The 63 eligible patients received 501 cycles. The
      mean dose intensity was 76%. At least one episode of WHO grade 3/4
      granulocytopenia was seen in 46% of the patients (13.6% of cycles). Significant
      nausea/vomiting was seen in only 5% of patients corresponding to 1% of cycles.
      Only 5% of patients developed WHO grade 3-4 constipation and grade 3 peripheral
      neuropathy was observed in 1.6% of patients. Alopecia was rare (6.3% of
      patients), and other side effects were uncommon. This study confirms that
      Navelbine has major single-agent antitumor activity as frontline therapy in
      advanced breast cancer. Given its excellent tolerance profile and low morbidity,
      it should be recommended for inclusion in first-line combination chemotherapy
      regimens.

PMID- 7572755
TI  - Aminothiadiazole in the treatment of advanced leiomyosarcoma of the uterine
      corpus. A Gynecologic Oncology Group study.
AB  - Aminothiadiazole was used to treat 21 patients with metastatic or recurrent
      leiomyosarcoma of the uterus. All patients received a starting dose of
      aminothiadiazole of 125 mg/m2 intravenously (30-to-45-minute infusion), which was
      repeated at weekly intervals. All patients also took allopurinol 300 mg per day
      orally to prevent hyperuricemia, a side effect of aminothiadiazole. Five patients
      (25%) had stable disease but there were no objective responses. Toxicity was
      generally mild with this regimen. There was no life-threatening toxicity and only
      three episodes of severe toxicity. One patient experienced both grade 3
      leukopenia and thrombocytopenia, while another patient had grade 3 nausea and
      vomiting. Further studies in this disease are not planned.

PMID- 7572757
TI  - The effect of epidermal growth factor mouthwash on cytotoxic-induced oral
      ulceration. A phase I clinical trial.
AB  - A double-blind clinical trial was performed to study the effect of epidermal
      growth factor (EGF) mouthwash on the healing and recurrence of oral ulceration in
      12 patients undergoing cancer chemotherapy. The oral distribution or cytotoxic
      induced ulcers corresponded to the salivary gutters. There was no difference in
      the rate of healing of established ulcers between the experimental and placebo
      groups. However, there was a small delay in the onset and severity of recurrent
      ulceration. It was concluded that EGF mouthwash does not accelerate ulcer
      healing, but it may have the potential to protect the oral epithelium from
      cytotoxic damage.

PMID- 7572756
TI  - Phase II trial of CHIP for the treatment of advanced, hormonally refractory
      carcinoma of the prostate. A Southwest Oncology Group Study.
AB  - CHIP, a second generation analogue of cisplatin, was subjected to a Phase II
      trial for the treatment of advanced, hormonally refractory carcinoma of the
      prostate. Forty-six patients were treated with CHIP 300 mg/m2 intravenously every
      4 weeks. Evaluations for tumor response were done after three cycles of therapy.
      Among 40 evaluable patients there were no complete responses, but there were 6
      partial responses for an overall response rate of 15% (95% confidence interval of
      5.7 to 29.8%). The median time to response was 2.4 months and the median
      progression-free survival was 4.1 months. Median survival was 8.4 months. The
      most common toxicities were hematologic and gastrointestinal. While CHIP can be
      administered on an outpatient basis, its response rate for prostatic carcinoma
      appears to be similar to that of cisplatin.

PMID- 7572758
TI  - Aromatase inhibitors: current status.
AB  - To review the aromatase inhibitors with emphasis on the newer agents that are
      being developed for the treatment of metastatic breast cancer. Review of English
      literature over the past 5 years using Med-Line and Cancer-Line computer search.
      All pertinent articles were included for this review. Source of estrogen in the
      human body and means of its ablation are discussed with emphasis on aromatase
      inhibition. Aminoglutethimide was highlighted as the prototype for inhibition of
      aromatase. All other agents that have aromatase inhibitory effect, as well as,
      antitumor effect were discussed in reference to their structure, chemistry,
      pharmacology, and pharmacokinetics in animals and humans. Their respective
      antitumor effect in experimental studies and humans, including dose-schedules
      responses and side effects, are also reviewed. New aromatase inhibitors have
      significant antitumor activity in breast cancer and may have better therapeutic
      index than currently available drugs.

PMID- 7572760
TI  - A phase II study of tamoxifen combined with cisplatin-interleukin 2 and alpha
      interferon in metastatic melanoma.
AB  - Tamoxifen (TAM) has been reported to enhance cisplatin (CDDP) cytotoxicity in
      experimental and clinical melanoma studies. Based on our previous experience with
      sequential cisplatin-interleukin-2 (IL2)-interferon (IFN), we performed a phase
      II study of TAM combined with our original CDDP-IL2-IFN regimen in 22 pretreated
      metastatic melanoma patients. With a 41% response rate (95% CI, 21-61) we
      confirmed the interesting antitumor activity of CDDP-IL2-IFN combination;
      however, TAM enhanced neither the response rate nor the duration of response, but
      appeared to induce significantly more myelotoxicity, as compared to our previous
      results with CDDP-IL2-IFN alone. Whereas mechanisms by which TAM may modulate
      CDDP cytotoxicity in melanoma tumors remain unknown, the exact place of TAM, if
      any, and its safety in chemotherapeutic or chemoimmunotherapeutic combinations
      require further investigations.

PMID- 7572759
TI  - Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide.
AB  - Merkel cell carcinoma is a rare malignant tumor of the skin. We treated three
      patients with Merkel call carcinoma with the combination of carboplatin and
      etoposide, which have been mostly used in the treatment of small cell lung
      carcinoma. Two patients experienced partial remission of short duration. The
      third patient received the combination on an adjuvant basis but relapse occurred
      briefly. Two of these patients failed to respond to second-line chemotherapy with
      cisplatin, ifosfamide, and epirubicin. The patient who had the first-line
      treatment on an adjuvant basis, responded completely with the second-line
      chemotherapy plus radiotherapy and remains disease-free for 5+months. Merkel cell
      carcinoma appears to be a sensitive tumor to chemotherapeutic regimens used for
      small cell lung carcinoma, but the responses are often brief.

PMID- 7572761
TI  - Combined application of cisplatin, vindesine, hyaluronidase and radiation for
      treatment of advanced squamous cell carcinoma of the head and neck.
AB  - In a prospective pilot study, 32 patients with advanced inoperable squamous cell
      carcinoma of the head and neck were treated with polychemotherapy and
      hyaluronidase combined with radiation therapy. Polychemotherapy consisted of 5 mg
      vindesine on day 1 and 80 mg/m2 cisplatin on day 2. The patients were given
      200,000 IU hyaluronidase intravenously 20 minutes prior to vindesine and
      cisplatin. Radiation in fractions of 2 Gy per day was administered on the
      following days (days 3-5, 8-12, 15-18), that is, 12 times. This regimen was
      repeated twice starting with day 22 and 43. Side effects were mainly of local
      character: moderate to severe mucositis in 10 patients and mild mucositis in 22
      patients. No severe systemic toxicity was observed. Complete remission was
      achieved in 27 of 32 patients. At present, 16 patients are alive and without
      relapse. The average time of follow-up is 47 months (range: 26-75 months). These
      preliminary results suggest that combined therapy with vindesine, cisplatin,
      hyaluronidase, and radiation are well tolerated by most patients and highly
      effective against advanced squamous cell cancer of the head and the neck.

PMID- 7572762
TI  - Randomized trial comparing oral ciprofloxacin plus penicillin V with amikacin
      plus carbenicillin or ceftazidime for empirical treatment of febrile neutropenic
      cancer patients.
AB  - Aminoglycoside-containing combination therapy has been the standard empirical
      approach for febrile neutropenic cancer patients. With the advent of the broad
      spectrum oral fluoroquinolones, it is now possible to evaluate an initial
      empirical alternative therapy. A prospective randomized study was conducted
      comparing oral ciprofloxacin plus penicillin V (group A) with amikacin plus
      carbenicillin or ceftazidime (group B). Main criteria for eligibility were
      febrile patients with solid tumor or nonlymphoblastic lymphoma, a Zubrod PS equal
      to 1 or 2, no diarrhea, mucositis, or long-term central venous catheter. A total
      of 108 consecutive neutropenic febrile episodes were randomized (5 exclusions);
      55 episodes were assigned to group A and 48 to group B. Most febrile episodes
      were of unknown origin. There were 10 microbiologically documented episodes with
      two cases of bacteremia. Both regimens were well tolerated. Oral regimen was
      substantially cheaper than parenteral regimen. Treatment success without regimen
      modification was 94.5% for group A and 93.8% for group B (p = .86; CI -0.08
      0.10). Oral therapy with ciprofloxacin and penicillin V is a safe alternative to
      standard parenteral therapy in this low-risk group of neutropenic patients, with
      unquestionable cost containment.

PMID- 7572763
TI  - Phase II trial of isotretinoin and recombinant interferon alfa-2a in metastatic
      colorectal carcinoma.
AB  - Phase II trials of the novel biologic combination isotretinoin (13-cis-retinoic
      aid) plus recombinant interferon alfa-2a have demonstrated this combination's
      major activity against advanced squamous cell carcinoma of the skin and cervix.
      Because this combination has had limited study in other tumors, we initiated a
      phase II trial of this regimen in patients with metastatic colorectal
      adenocarcinoma. Sixteen patients with measurable metastatic colon carcinoma who
      had received no previous chemotherapy were entered on the trial. Patients
      received recombinant interferon alfa-2a, 6 million units a day subcutaneously,
      and isotretinoin, 1 mg/kg per day orally in two divided doses. Patients were
      evaluated for response after 8 weeks of treatment and then continued on therapy
      until progressive disease was documented. We did not observe complete or partial
      responses. Two patients experienced minor responses in measurable pulmonary
      metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5
      patients), granulocytopenia (6 patients), neurotoxicity (2 patients), and
      elevated serum triglyceride levels (2 patients). Although this combination has
      demonstrated significant activity in squamous cell carcinomas of the skin and
      cervix, our results suggest that it has little therapeutic activity against
      advanced colorectal adenocarcinomas.

PMID- 7572764
TI  - A phase II study of fazarabine (NSC 281272) in patients with advanced squamous
      cell carcinoma of the cervix. A Gynecologic Oncology Group study.
AB  - Promising preclinical data and reasonable toxicity in Phase I trials encouraged
      the Gynecologic Oncology Group to study Fazarabine (FZB) in patients with
      recurrent squamous cell cancer of the cervix. Twenty-three patients with
      histologically proven recurrent cervical cancer with measurable disease received
      FZB at a dosage of 30 mg/m2 per day for 5 days; cycles repeated every 28 days. In
      the absence of grade 3 or 4 toxicity, dose escalation was planned to a maximum
      dose of 40 mg/m2 per day for 5 days. All patients were evaluable for toxicity.
      Seven patients developed neutropenia; in two instances, it was considered life
      threatening. The only other serious adverse effect was seen in one patient who
      developed grade 4 nephrotoxicity. Nineteen women who had failed prior
      chemotherapy were evaluable for response. There were no complete or partial
      responses; and seven had stable disease. Fazarabine exhibits no demonstrable
      activity in this patient population at the dose and schedule tested and further
      clinical trials as second-line chemotherapy are not warranted.

PMID- 7572766
TI  - Acute myocardial infarction in man treated with epirubicin for non-Hodgkin
      lymphoma.
AB  - This article presents a young patient affected with non-Hodgkin lymphoma who
      developed acute myocardial infarction 7 days after treatment with epirubicin (90
      mg/m2, day 1), cyclophosphamide (600 mg/m2, day 1), vincristine (2 mg, day 1),
      prednisolone (100 mg, days 1-5), and ondansetron (3 x 4 mg/day, days 1-2). Six
      months after the myocardial infarction the patient had no further cardiac
      complications after treatment with cylcophosphamide, vincristine, and ondansetron
      chemotherapy regimen. Epirubicin was considered to play an important role in the
      production of infarction, and the probable mechanisms of epirubicin-induced
      myocardial infarction are discussed.

PMID- 7572765
TI  - A phase II trial of merbarone (NSC 336628) as salvage therapy for squamous cell
      carcinoma of the cervix. A Gynecologic Oncology Group Study.
AB  - Twenty-seven patients with previously irradiated unresectable recurrent squamous
      carcinoma of the cervix who had failed one prior cytotoxic regimen received 1,000
      mg/m2 per day of merbarone given by continuous i.v. infusion for 5 days every 4
      weeks through a central line. One patient was never treated, and four were
      inevaluable for response, leaving 26 patients evaluable for toxicity and 22
      evaluable for response. The major adverse effect was myelosuppression with 6/26
      (23%) experiencing Gynecologic Oncology Group (GOG) grade 3 or 4 leukopenia.
      There were two episodes (3.8%) of GOG grade 3 SGOT elevation. There were two
      patients (9.0%) who developed mental status changes classified as grade 3
      neurotoxicity. This neurotoxicity may have been secondary to iatrogenic
      hyponatremia caused by the large volumes of 5% glucose infusion required at the
      original infusate concentration. After the concentration of the merbarone
      infusate was increased to 4 mg/ml, no further problems with hyponatremic
      neurotoxicity were encountered. The overall response rate was 2/22 (9.0%) (95%
      confidence interval 1.1-29.2%). In this pretreated population with recurrent
      squamous cervical carcinoma, merbarone exhibited only minimal activity.

PMID- 7572767
TI  - Accelerated hyperfractionated radiation therapy for malignant glioma. A phase II
      study.
AB  - Sixty-four adult patients with malignant glioma entered into a Phase II study on
      the use of accelerated hyperfractionated radiation therapy. Histology included
      anaplastic astrocytoma (AA) in 15 patients and glioblastoma multiforme (GBM) in
      49 patients. Treatment consisted of radiation therapy doses of 66 Gy in 44
      fractions in 22 treatment days in 4.5 weeks, fractions of 1.5 Gy, b.i.d. 1,3
      bis(2-chlorethyl)-1-nitrosourea (BCNU) 80 mg/m2 and hydroxyurea 800 mg/m2 were
      both given on treatment days 1, 6, 11, 16, and 21 during the irradiation course.
      Median survival time for all 64 patients is 61 weeks (range; 12-163 weeks) from
      the date of starting irradiation. Median time to tumor progression (MTP) for GBM
      patients is 31 weeks, and 1-year and 3-year progression-free survival (PFS) are
      16% and 0%, respectively, while MTP for AA patients is not attained yet, and 1
      year and 3-year PFS are 100% and 73%, respectively. On univariate analysis of
      prognostic factors for GBM patients, younger age, total or subtotal tumor
      removal, and frontal tumor location are associated with a better prognosis. A
      multivariate analysis confirmed the importance of the extent of surgery and tumor
      site and revealed the interfraction interval (4.5-5.0 hours vs 5.5-6.0 hours, p =
      .041) as an important prognostic factor. Acute and late toxicity is not
      increased. Longer follow-up and more patients are needed to evaluate tumor
      control and toxicity in AA patients.

PMID- 7572769
TI  - Management of the axilla in patients with breast cancers one centimeter or
      smaller.

PMID- 7572771
TI  - Changes of cerebral endogenous evoked potentials by acupuncture stimulation: a
      P300 study.
AB  - The change of cerebral potential P300 in relation to superior cerebral functions
      by means of acupuncture stimulation was studied. For this purpose, the parameters
      of this cerebral response after acupuncture stimulation at acupoints He-7 and LI
      4, and at a non-acupuncture control point, have been assessed, both immediately
      after the stimulation and within the following 15 minutes. A considerable change
      is observed in the P300 amplitude after stimulation at He-7 acupoint, which
      increases with time. No changes due to non-acupuncture point stimulation or LI-4
      acupoint stimulation are detected. These findings seem to support the real action
      of He-7 in different neuropsychological processes.

PMID- 7572768
TI  - Prognostic implications of chemoresistance-sensitivity assays for colorectal and
      appendiceal cancer.
AB  - A major problem with pharmacologic treatments for cancer is the unpredictable
      nature of the clinical response. Therefore, many patients are treated but few
      benefit from chemotherapy. Selection of patients for drug treatment would greatly
      benefit both responders and nonresponders. Mitomycin C (MMC) and 5-fluorouracil
      (5-FU) are important drugs widely used in the treatment of patients with
      gastrointestinal malignancies. In a prospective study, an in vitro
      chemoresistance-sensitivity assay (CR-SA) was performed for 95 patients at the
      time of surgery for peritoneal carcinomatosis from colorectal and appendiceal
      cancer. Following cytoreductive surgery, all of these patients had minimal-to
      moderate residual disease. All patients were treated with the same chemotherapy
      regimen regardless of the results of the in vitro assay in the postoperative
      period. Clinical status of patients was correlated to the assay predictions, and
      the results were statistically evaluated. When resistance was correlated with
      outcome, there was no statistical difference. In addition, the mean percentage of
      growth inhibition was not increased when responders and nonresponders were
      compared. Finally, more patients who had > or = 95% in vitro growth inhibition of
      cancer did not survive than did those with < or = 95% growth inhibition. The in
      vitro test did not predict sensitivity or resistance to cancer when regional
      chemotherapy was administered in a clinical setting of peritoneal carcinomatosis.

PMID- 7572772
TI  - Effect of acupuncture at Tsu San Li (St-36) on the pulse spectrum.
AB  - Effect of acupuncture at Tsu San Li (St-36) was examined by investigating the
      pulse variation of the radial artery. Our results indicated that acupuncture at
      Tsu San Li has a specific effect on the Fourier components of the pulse. The
      harmonic proportions were redistributed (C2, C4 decreased, C5, C6, C8 and C9
      increased), and the phase angle of the 5th and 8th harmonic waves were decreased
      (propagating faster). This specific frequency effect was not found when
      acupuncture needle was applied on a non-acupuncture point. These results can be
      explained by the resonance theory, which provides a scientific explanation of the
      acupuncture effect from the hemodynamic view point.

PMID- 7572770
TI  - A single-blind investigation of four auricular needle puncture configurations.
AB  - In order to identify an appropriate needle puncture control for clinical trials
      of acupuncture we conducted a study in which ten cocaine dependent subjects rated
      local and systemic effects of four auricular needle puncture configurations (a)
      sites commonly used for addiction; (b) sites proximate to addiction specific
      sites; (c) sites not specific for cocaine addiction; and (d) sites in the helix.
      Subjects received one treatment per day on four successive days. The addiction
      specific sites were rated highest on local effects; proximal sites a common
      control were rated highest on systemic effects. A majority of patients ranked the
      addiction specific sites as the most preferred treatment and the helix points as
      the least preferred. Results suggest that needle insertion into proximate and non
      specific sites may be too active for use as controls; helix regions may be more
      suitable.

PMID- 7572773
TI  - Acupuncture protection against experimental hyperbilirubinemia and cholangitis in
      rats.
AB  - Effects of acupuncture on experimental hyperbilirubinemia and cholangitis were
      studied in male rats (n = 33). The experimental group were treated with
      acupuncture, 18, 12 and 6 hr prior to and 6, 12 and 18 hr after oral
      administration of alpha-napthylisothiocyanate (ANIT, 100 mg per Kg). Rats were
      sacrificed 48 hours after challenge. Serum and liver samples were taken for
      biochemical and histological analysis, respectively. Results of this study
      revealed that rats treated with ANIT exhibited elevations in bilirubin, SGOT and
      SGPT as well as cholangitis. In rats receiving acupuncture and ANIT, biochemical
      and morphological parameters of liver injury were significantly reduced.
      Acupuncture therapy may be able to prevent ANIT-induced hyperbilirubinemia and
      cholangitis.

PMID- 7572776
TI  - Effect of liu-junzi-tang on the symptom of bitter taste in patients with chronic
      gastritis.
AB  - A symptom of bitter taste was found in 15 out of 82 patients with chronic
      gastritis that was diagnosed from symptoms and endoscopic findings. Liu-junzi
      tang was very effective in 12 (80%) of the 15 patients. The symptom of bitter
      taste completely disappeared in 24.7 days on average after oral administration of
      Liu-junzi-tang in these 12 patients. In the remaining 3 patients, the symptom of
      bitter taste did not completely disappear, but was improved. Other symptoms
      associated with chronic gastritis and endoscopic findings were also improved in
      these patients. These findings indicate that Liu-junzi-tang may be a good remedy
      for the symptom of bitter taste in patients with chronic gastritis.

PMID- 7572774
TI  - Delayed cutaneous hypersensitivity reactions in Qigong (chun do sun bup) trainees
      by multitest cell mediated immunity.
AB  - To determine the difference of cellular immunity between a Qigong trainee group
      and a normal healthy group, skin tests for delayed cutaneous hypersensitivity
      (DCH) were carried out with ubiquitous seven antigens. The maximal antigen
      response time was faster in Qigong trainee group (24 hr) and the response antigen
      number was also higher in the Qigong trainee group (6 antigens) than in normal
      healthy person (48 hr and 4 antigens). Qigong trainee also had a larger
      induration diameter (5.14 mm) than normal healthy person (3.79 mm) at 24 hr. Our
      results represent the difference in cell mediated immunity (CMI) between Qigong
      trainees and normal healthy subjects.

PMID- 7572775
TI  - The anti-inflammatory effects of Chinese crude drug prescriptions on experimental
      arthritis.
AB  - San-Miao-Warn (SMW), Tuhwo-Jih-Shen-Tang (TJS) and Dang-Quei-Nian-Tong-Tang (DGT)
      are Chinese traditional prescriptions. In this study, we evaluated the anti
      inflammatory activities of these crude drug prescriptions in carrageenan-induced
      acute arthritis and complete Freund's adjuvant (CFA)-induced chronic arthritis in
      rats. It was found that pretreatment with SMW, TJS or DGT at a dosage of 100
      mg/kg or 300 mg/kg, significantly inhibited carrageenan-induced acute arthritis.
      Moreover, these crude drugs also significantly suppressed the development of
      chronic arthritis induced by CFA. These results suggest that SMW, TJS and DGT are
      potential anti-inflammatory agents and may be considered as alternatives for non
      steroid anti-inflammatory drugs (NSAID).

PMID- 7572777
TI  - Improvement by guan-mu-tong (Caulis aristolochiae manshuriensis) of lactation in
      mice.
AB  - Free access of 0.5% Guan-mu-tong (Gmt) as drinking water inhibited lactation of
      mice estimated by pup growth rate, which was associated with a decrease in RNA
      content and RNA/DNA ratio in the mammary glands. 0.05% Gmt improved pup growth
      rate and mammary DNA content. No pups were lost during the experiment. Similar
      results were obtained by 0.5% Xia-ru-yong-quan-tang (Xryqt), a Chinese herbal
      medicine, which contained 0.05% Gmt. Xryqt further prevented a decline in ovarian
      weight seen by 0.05% Gmt treatment and significantly increased mother weight.
      These findings revealed two opposite effects of Gmt on mammary glands,
      stimulative and inhibitory, at low- and high-dose levels, respectively.

PMID- 7572778
TI  - Effects of ginseng on the blood chemistry profile of dexamethasone-treated male
      rats.
AB  - Ginseng, a panacea in the Orient, has been widely investigated in the last two
      decades and found to possess a wide range of pharmacological activities including
      anti-fatigue properties, a transient regulatory action on metabolism and blood
      pressure, and an increase in the hypothalamo-pituitary-adrenocortical activities.
      However, a panoramic clinical chemistry study including adrenal and thyroid
      functions has never been done before. Two experiments with the same design but
      different concentrations of dexamethasone were performed in this study. The
      results obtained from the two experiments indicated that ginseng administration
      at this regime did not influence the blood chemistry profiles in normal rats, but
      significantly decreased AST and ALT levels from those in dexamethasone-treated
      ones. It implies that ginseng has a liver-protective effect. Meanwhile, ginseng
      therapy restores the adrenal and thyroid functions of rats inhibited by
      dexamethasone treatment.

PMID- 7572779
TI  - The effect of Evodia rutaecarpa extract on cytokine secretion by human
      mononuclear cells in vitro.
AB  - The effect of Evodia rutaecarpa extract on cytokine secretion by human
      mononuclear cells in vitro was investigated. Evodia rutaecarpa extract of various
      concentrations in mononuclear cell culture medium showed biphasic effects on the
      secretion of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis
      factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor
      (GM-CSF) by the mononuclear cells. Generally speaking, a low to medium level of
      Evodia rutaecarpa extract, in concentrations ranging from 10% to 30%, showed
      significant stimulating effects on the secretion of IL-1 beta, IL-6, TNF-alpha
      and GM-CSF. On the other hand, high level of Evodia rutaecarpa extract, with
      concentration more than 40%, lost its stimulating effects. Moreover, reaction
      time affected the stimulating effects of Evodia rutaecarpa extract on cytokine
      secretion by mononuclear cells. Mononuclear cell culture medium containing Evodia
      rutaecarpa extract that was allowed to react for 18 or 24 hours showed
      significantly better stimulating effects than that reacted for 1 or 3 hours.

PMID- 7572780
TI  - Studies on the agronomic characteristics, yield, and saikosaponin content of two
      Bupleurum species in Taiwan.
AB  - Two Bupleurum species (Bupleurums spp.), i.e., B. falcatum L. cv. Tainung No. 1
      and B. kaoi Liu, Chao, et Chuang, were compared for their differences in seed
      germination, plant characteristics and root yield, and saikosaponin content.
      Experimental data showed that the most suitable temperature for seed germination
      of the two species was 16 degrees C. Two treatments, cold stratification at 4
      degrees C for 8 weeks and presoaking by running water for 2 days, resulted in
      higher germination rates. Tainung No. 1 possessed a higher 1,000-seed weight than
      B. kaoi. However, field survival rate was higher for B. kaoi than for Tainung
      No.1. Results from field experiments also revealed that stem diameter, leaf width
      and fresh weight of various plant parts except the root were superior for Tainung
      No. 1 to B. kaoi. On the contrary, tiller number and root diameter and weight of
      B. kaoi were higher than those of Tainung No. 1. Harvest data and elevation had
      significant effects on the agronomic performance of the two Bupleurum spp.
      Measurements of most traits of the 6 month-old plants were superior to those of
      the 3 and 10 month-old plants. Cultivation at higher elevation (850 m) favored
      the development of leaf weight and root length, while cultivation at lower
      elevation (85 m) facilitated the development of plant height, root diameter, and
      root weight. Analysis of saikosaponin concentration in the root tissue revealed
      that average contents of 3.19 and 3.80 mg/g, respectively, for plants grown at
      the elevations of 850 m and 85 m. Comparison between the two species showed no
      significant difference in saikosaponin content, ranging from 3.45 to 3.55 mg/g.

PMID- 7572782
TI  - Guardians of the wax ... and the patient.

PMID- 7572781
TI  - Traditional Chinese medicines improve the course of refractory leukemic
      lymphoblastic lymphoma and acute lymphocytic leukemia: two case reports.
AB  - A 34 year-old man with leukemic lymphoblastic lymphoma (LBL), who could not
      tolerate chemotherapy due to its side effects, was diagnosed to have an acute
      febrile disease by a traditional Chinese medical doctor, Lu Gan Fu. Zixuedan, a
      traditional Chinese remedy for dissipation of pathogenic heat and detoxification
      that could reduce WBC count including leukemic cells below 1000/microliters
      without intolerable side effects, was prescribed for treatment. A second case of
      acute lymphocytic leukemia (ALL) was a 41 year-old female who also could not
      tolerate chemotherapy. In her fourth recurrence, she started Chinese medicine
      including modified zixuedan, which gave her transient improvement followed by
      aggravation. Intake of previously ineffective cyclophosphamide in combination
      with Chinese medicine led to a dramatic improvement.

PMID- 7572783
TI  - Hodgkin's disease. Lineage and clonality.

PMID- 7572784
TI  - Recommendations for the reporting of resected primary lung carcinomas.
      Association of Directors of Anatomic and Surgical Pathology.

PMID- 7572785
TI  - p53 protein expression and p53 gene mutation in thymic epithelial tumors. An
      immunohistochemical and DNA sequencing study.
AB  - p53 protein expression in 34 thymic epithelial tumors was examined
      immunohistochemically, and p53 gene mutation was detected in selected cases by
      DNA sequencing, using formalin-fixed and paraffin-embedded tissues. The tumors
      comprised 12 noninvasive thymomas, 9 invasive/metastatic thymomas, and 13 thymic
      carcinomas. All the tumors were immunoreactive for p53 protein. The p53-positive
      tumor cells in noninvasive thymoma were less than 10% (low expressor) in 7 cases
      and 10% to 50% (moderate expressor) in 5 cases. In invasive/metastatic thymoma,
      two were low expressors and seven were moderate expressors. In thymic carcinomas,
      there were nine moderate expressors and four high expressors (with > 50% positive
      cells). There was significant difference in p53 protein immunopositivity between
      thymic carcinoma and each of the noninvasive or invasive/metastatic thymomas. The
      DNA sequencing study confirmed the presence of p53 gene point mutation in all 10
      cases examined, including three low expressors. These results suggest that p53
      gene mutation is an early event in thymic tumorigenesis, and the p53 protein
      positive cells increase with the progression of the tumor. Immunostaining
      reactivity of p53 may be a useful adjunct to differentiate thymic carcinoma from
      thymoma.

PMID- 7572786
TI  - Adrenal cortical tumors clinically mimicking pheochromocytoma.
AB  - The authors report five patients with adrenal cortical tumors in whom the
      preoperative diagnosis of pheochromocytoma was made. All patients had biochemical
      evidence of elevated catecholamine secretion in serum or urine. Clinically, two
      patients presented with symptoms suggestive of pheochromocytoma, and one patient
      had systemic hypertension that resolved following surgical excision of the tumor.
      Histologically, the findings were typical of adrenal cortical tumors: two adrenal
      cortical carcinomas and three adrenal cortical adenomas. Nevertheless, the
      immunohistochemical studies showed evidence of neuroendocrine differentiation in
      four tumors. Three tumors were positive for neuron-specific enolase and
      synaptophysin and a fourth tumor was positive for synaptophysin only. All
      neoplasms were negative for chromogranin. Electron microscopic studies in three
      tumors showed abundant endoplasmic reticulum and tubulovesicular cristae
      consistent with adrenal cortical cell origin. Neurosecretory granules, 150-300 mu
      in diameter, were found in one tumor. This current series of patients provides
      evidence that adrenal cortical neoplasms may be associated with clinical findings
      that simulate pheochromocytoma (so-called pseudo-pheochromocytoma). These
      clinical findings may be mediated by the presence of neuroendocrine features in
      these tumors.

PMID- 7572787
TI  - Aggressive angiomyxoma in males. A report of four cases.
AB  - Aggressive angiomyxoma (AAM) is a rare, locally infiltrative but nonmetastasizing
      tumor of the pelvic and perineal soft tissues that occurs almost exclusively in
      adult females. The authors describe four cases of AAM in adult males that arose
      in the scrotum. There was some histologic variation among the tumors. One case
      was focally hypercellular around the blood vessels, two were more densely
      cellular throughout, and one had cystic degeneration. Three of the tumors were
      widely infiltrative, and one of the four tumors recurred locally. The
      clinicopathologic features of these cases are similar to those of AAM occurring
      in females. In either sex, AAM should be distinguished from benign myxoid tumors
      with a low risk of local recurrence and fully malignant myxoid tumors with
      distant metastatic potential.

PMID- 7572788
TI  - Immunohistochemical detection of tartrate-resistant acid phosphatase in non
      hematopoietic human tissues.
AB  - Immunohistochemical studies were done on formalin-fixed, paraffin-embedded
      tissues to evaluate the specificity of a newly developed monoclonal antibody
      (9C5) against tartrate-resistant acid phosphatase. Sections from 195 specimens
      were examined, which included 33 types of tissues/organs. These tissues included
      normal, inflammatory, and neoplastic processes. Neoplastic tissues from 14
      patients with hairy cell leukemia served as positive controls. Epitope
      enhancement was accomplished either by microwave irradiation in citrate buffer or
      by boiling in water followed by trypsin digestion. Tissues were reacted with
      monoclonal antibody 9C5 and stained with either the avidin-biotin peroxidase
      method or the alkaline phosphatase anti-alkaline phosphatase method. The hairy
      cells of all cases of hairy cell leukemia reacted positively with 9C5. Other
      positively stained cells included osteoclasts, activated macrophages and giant
      cells. Immunohistochemical studies with 9C5, when interpreted within the context
      of the specificity of this antibody, are useful for the diagnosis and assessment
      of treatment results for hairy cell leukemia. Monoclonal antibody 9C5 also may be
      useful as a marker for osteoclasts and the activated macrophages and for the
      diagnosis of disorders involved by these cells.

PMID- 7572790
TI  - Ectopic poorly differentiated (insular) carcinoma of the thyroid. Report of a
      case presenting as an anterior mediastinal mass.
AB  - A case is presented of an anterior mediastinal mass arising in a 64-year-old
      woman that showed on histologic, immunopathologic, and ultra-structural
      examination features of a poorly differentiated (insular) thyroid carcinoma. The
      tumor in this patient most likely arose from ectopically displaced thyroid tissue
      on the basis of a developmental defect. The clinicopathologic features and
      differential diagnosis of the lesion in the setting of its mediastinal location
      are discussed. Ectopic poorly differentiated (insular) carcinoma of the thyroid
      should be added to the list of mediastinal tumors showing a solid or insular
      growth pattern.

PMID- 7572789
TI  - Aggressive fibromatosis of the spermatic cord. A typical lesion in a "new"
      location.
AB  - The authors describe a 31-year-old man with a 7 cm aggressive fibromatosis
      (desmoid tumor) of the spermatic cord presenting as a swelling in the left
      inguinal area that was excised along with the testis and cord. The desmoid tumor
      is histologically typical, but such tumors arising primarily from the
      paratesticular structures have apparently not been previously reported and the
      diagnosis would not be questioned if it not for the unusual site. This tumor is
      histologically and immunohistochemically indistinguishable from abdominal wall
      desmoid tumor, with or without Gardner's syndrome. Desmoid tumors at this
      location should be distinguished from reactive processes, such as
      pseudosarcomatous myofibroblastic proliferation (so-called "proliferative
      funiculitis") and inflammatory fibrous pseudotumor, all of which exhibit
      fibroblastic/myofibroblastic differentiation. Paratesticular fibrosarcoma and
      leiomyosarcoma should also be differentiated from desmoid tumor that does not
      have the metastatic potential of sarcomas. Thirty-four months post-operatively,
      an 8 cm local recurrence in the remaining portion of the left vas deferens
      causing left hydroureter and hydronephrosis was detected.

PMID- 7572791
TI  - Correlation between presence of clonal rearrangements of immunoglobulin heavy
      chain genes and B-cell antigen expression in Hodgkin's disease.
AB  - Southern blot analysis of Hodgkin's disease (HD), although often compromised by
      the small number of abnormal cells present in the tissue, have tended to favor a
      B-cell derivation of the Hodgkin's and Reed-Sternberg (HRS) cells in cases of
      nodular sclerosis (NS) and mixed cellularity (MC) Hodgkin's disease. Eighteen
      frozen and 29 paraffin-embedded sections of lymph node specimens from 29 patients
      with pretreatment HD (22 NSHD and 7 MCHD) were studied by molecular analysis and
      immunohistochemistry to determine the phenotype of HRS cells. All cases were
      reviewed and showed typical morphology and CD45-, CD30+, CD15+, BLA.36+ HRS
      cells. In 11 of 29 (38%) cases, HRS cells were reactive with at least one B-cell
      marker (CD20, CD79a, MB2), 7 of 29 (24%) cases showed reactivity with the T-cell
      marker CD3, and 11 of 29 (38%) cases displayed a "null" phenotype. By using a
      polymerase chain reaction (PCR) and consensus primers for the V and J regions of
      the immunoglobulin heavy chain (IgH) gene, the authors were able to detect B-cell
      clonality in 9 of 18 (50%) frozen samples of HD analyzed. IgH gene rearrangement
      was present in 8 of 15 (53%) NSHD and in 1 of 3 (33%) MCHD. In five of nine (56%)
      of these cases, HRS cells were reactive with at least one B-cell marker, whereas
      one case expressed the T-cell marker CD3. The other three cases with IgH gene
      rearrangement showed a "null" immunophenotype. IgH gene analysis was negative in
      all remaining CD3+ cases and in two other cases that expressed B-cell markers by
      immunohistology. Southern blotting failed to detect rearrangement of the T-cell
      receptor beta-chain gene and immunoglobulin heavy and light genes in any of these
      cases. The results show that PCR represents a specific and sensitive technique
      for the detection of IgH gene rearrangements in cases of Hodgkin's disease. The
      results also suggest a lymphoid B-cell derivation of HRS cells in a high
      proportion of the cases.

PMID- 7572792
TI  - Clonal VDJ recombination of the immunoglobulin heavy chain gene by PCR in
      classical Hodgkin's disease.
AB  - Although Hodgkin's disease (HD) has been a subject of much investigation,
      fundamental questions remain unanswered regarding its lineage and clonality. The
      authors used a polymerase chain reaction (PCR) technique to investigate whether
      clonal Variable-Diversity-Joining recombination of the immunoglobulin heavy (IgH)
      chain gene, a phenomenon that characterizes clonal B-cell proliferations, exists
      in nodular sclerosing (NSHD) and mixed cellularity (MCHD) Hodgkin's disease (so
      called "classical" Hodgkin's disease). The isolation of DNA from paraffin
      embedded tissue sections allowed for direct correlation of PCR results with the
      cell populations that were analyzed. Thirty-two cases were studied. These
      included 12 cases in which the Reed-Sternberg (RS) cells expressed the B-cell
      antigen, CD20, and 10 cases that were classified as syncytial variant of NSHD (3
      CD20+, 7 B-cell antigen negative). Overall, clonal patterns of VDJ PCR products
      were found in 14 of 32 (44%) cases. These clonal patterns were identified in 7 of
      12 (58%) cases of CD20+ classical HD and in 7 of 20 (35%) cases of B-antigen
      negative classical HD. Clonal patterns were found in 3 of 10 cases of syncytial
      variant of NSHD, including 2 of 3 (67%) CD20+ cases and 1 of 7 (14%) B-cell
      antigen-negative cases. The results of this study provide support that a subset
      of HD represents a clonal B-cell neoplasm, and indicate that clonal IgH VDJ
      sequences are more frequently found in CD20+ HD.

PMID- 7572793
TI  - Search for rearrangements and/or allelic loss of the fas/APO-1 gene in 101 human
      lymphomas.
AB  - The authors analyzed the possible occurrence of rearrangements and/or allelic
      loss of the fas/APO-1 gene in a representative series of human lymphomas,
      including 101 cases of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL).
      The rationale for this study was double. Chromosome 10 alterations, frequently
      observed in lymphoma subtypes, encompass the chromosomal localization of fas/APO
      1. In addition, Ipr mouse mutants, which present with a generalized
      lymphoproliferative disease, were shown to exhibit alterations of fas/APO-1
      structure and expression. In this retrospective study, the authors performed gene
      dosage of fas/APO-1 by Southern blots. No fas/APO-1 alterations were observed in
      the 31 HD cases. Among 70 T-cell and B-cell NHL, allelic loss of fas/APO-1 was
      observed in three cases. Two cases with different clinical, phenotypic, and
      histologic presentations showed a rearrangement of fas/APO-1. A third case showed
      amplification. Thus fas/APO-1 alterations do occur in human lymphomas, although
      at a relatively low frequency.

PMID- 7572794
TI  - Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology
      in diagnosis and classification.
AB  - The diagnosis of primitive hematologic malignancies in extramedullary sites
      (lymphoblastic lymphoma of T- or B-cell type and myeloid sarcoma) on paraffin
      embedded tissue sections is difficult and often impossible because of the
      primitive morphology of the neoplastic cells. The authors studied 21
      extramedullary tumors of lymphoid or myeloid blasts. They used a panel of 22
      antibodies on frozen sections and 9 antibodies on paraffin sections to determine
      the spectrum of immunophenotypes and to develop a practical panel for diagnosis.
      All but two of the cases could be classified as lymphoid or myeloid using
      immunohistologic analysis. Thirteen cases were classified as lymphoblastic
      lymphoma/acute lymphoblastic leukemia (LBL/ALL); 10 were classified as precursor
      T (CD7+, CD3+/-, CD45+) and 3 as precursor B-cell (CD19+/-CD10+CD45-) type. Five
      cases were classified as myeloid sarcoma (CD13+ myeloperoxidase+, lysozyme+). Two
      LBL/ALL coexpressed either CD33 (1 case) or CD15 (1 case), and one myeloid
      sarcoma coexpressed TdT and CD7. One case appeared to be truly mixed lineage,
      coexpressing CD3 with myeloperoxidase and lysozyme, and two cases expressed no
      lineage-specific antigens. There were clinical differences between the three
      major tumor types, and within the category of T-precursor LBL/ALL, classification
      according to stage of thymocyte differentiation was associated with distinctive
      clinical features. In conclusion, the spectrum of immunophenotypes detected on
      frozen section was similar to that reported by flow cytometry on peripheral blood
      and bone marrow specimens. The most useful antigens on frozen sections were CD7
      and CD3 (T cell), CD10 and CD19 (B cell), and CD13 (myeloid). TdT was coexpressed
      by one myeloid sarcoma and was undetectable in 40% of LBL/ALL. On paraffin
      sections, myeloperoxidase and lysozyme were reliable markers of myeloid lineage,
      but none of the markers used on paraffin sections distinguished between LBL/ALL
      of T- and B-precursor types. Both B-LBL/ALL and myeloid sarcomas were often CD45-
      on paraffin sections, which may be a obstacle in determining the diagnosis. These
      distinctions appear to have clinical relevance.

PMID- 7572795
TI  - Hemoglobin Sherwood Forest detected by high performance liquid chromatography for
      hemoglobin A1c.
AB  - Hb Sherwood Forest has been so far identified in only one patient in 1977. This
      study describes the second detection of this hemoglobin variant by routine high
      performance liquid chromatography (HPLC) in a diabetic patient and her healthy
      grand niece. In both, glycosylated hemoglobin (HbA1c) values were excessively
      elevated (52%), as determined by HPLC with a cation exchange column. The latex
      agglutination test showed values of HbA1c in the expected normal range. Citrate
      agar electrophoresis revealed a hemoglobin variant with a mobility similar to
      HbF. Amino acid analysis and DNA sequence analysis revealed an Arg-->Thr exchange
      at codon 104 of the beta-chain. This sequence has been described as Hb Sherwood
      Forest in 1977. The hemoglobin variant is clinically silent and might be confused
      with excessively high HbA1c in routine measurement of glycosylated hemoglobin.

PMID- 7572796
TI  - Heparin contamination in coagulation testing and a protocol to avoid it and the
      risk of inappropriate FFP transfusion.
AB  - Artifactual heparin contamination of blood samples drawn for coagulation testing
      is an ongoing problem. A retrospective analysis of activated partial
      thromboplastin times (APTTs) greater than 45 seconds from patients on neither
      heparin nor Coumadin (Dupont, Wilmington, DE) therapy shows complete correction
      of the APTT to normal in 39% of such samples after treatment with heparinase.
      Recheck of samples with significantly prolonged APTTs after treatment with
      heparinase is proposed as the best method to avoid inappropriate transfusion of
      fresh frozen plasma.

PMID- 7572797
TI  - Prevalence and patient profile in activated protein C resistance.
AB  - Activated protein C resistance (APC-R) is a recently defined abnormality of the
      coagulation system predisposing to the development of a hypercoagulable state.
      The authors have attempted to evaluate the prevalence and clinical manifestation
      of APC-R by studying a population of 183 patients with a history of venous
      thromboembolic episodes. Laboratory evaluation of APC-R was performed using the
      test initially described by Dahlback and colleagues based on the activated
      partial thromboplastin time (APTT) with the Coatest APC resistance kit
      (Chromogenix, Sweden) on KC10 coagulometer (Amelung, Germany). These results
      showed a 13% prevalence of APC-R as demonstrated by an APC ratio below 2.0. The
      male-to-female ratio was 1:7. Most of the thrombotic episodes were deep venous
      thromboses (50%).

PMID- 7572799
TI  - Severe intravascular hemolysis associated with brown recluse spider envenomation.
      A report of two cases and review of the literature.
AB  - Envenomation by the brown recluse spider (loxoscelism) is classically associated
      with a necrotic ulcer. Systemic manifestations occur in a minority of cases, but
      are generally mild and self-limited. The hematologic complications of brown
      recluse spider bite range from mild hemolysis to fulminant intravascular
      hemolysis with or without evidence of disseminated intravascular coagulation.
      Intravascular hemolysis is a rare but occasionally lethal complication of brown
      recluse spider envenomation. This article presents two cases of severe hemolysis
      associated with loxoscelism occurring in two young women in Memphis, Tennessee.
      The second documented death in an adult from severe hemolysis due to a brown
      recluse spider bite is reported. A review of the literature emphasizing the
      pathogenic mechanisms of spider bite hemolysis is also included.

PMID- 7572800
TI  - The effects of heparin on lipoproteins in high-resolution electrophoresis of
      serum.
AB  - Sera from heparinized patients commonly display anodal slurring of both the alpha
      and beta lipoproteins when they are examined by high-resolution electrophoresis
      (HRE). In this study, the authors examined the effect of heparin and lipoprotein
      lipase on the electrophoretic migration of alpha and beta lipoproteins in sera.
      The addition of 10 to 1,000 units of heparin/mL to normal sera resulted in a
      concentration-dependent anodal slurring of the beta lipoproteins. At 40 units/mL,
      the beta lipoprotein band was not visible when the Paragon blue protein stain was
      used. The beta lipoprotein could be seen as a wide, faintly staining band with
      lipoprotein stain. The alpha lipoprotein band on the same gel was unaffected by
      the added heparin. High-resolution electrophoresis of other sera from patients
      who were therapeutically heparinized demonstrated anodal slurring of both alpha
      and beta lipoproteins independent of heparin concentration. Immunofixation
      electrophoresis (IFE) studies confirmed that apolipoproteins A and B were slurred
      within their respective bands. Heparin activates lipoprotein lipase with release
      of free fatty acids (FFA) from very low density lipoproteins and chylomicrons. To
      test this effect on migration, sera were incubated with lipoprotein lipase in
      vitro. The anodal slurring of both the alpha and beta lipoprotein was associated
      with the amount of FFA production. Individuals interpreting electrophoretic
      patterns should be aware that both the alpha and beta lipoproteins can migrate
      and slur anodally in heparinized patients. In addition, when the beta lipoprotein
      band interferes with the identification of monoclonal gammopathies, its migration
      can be selectively altered by the addition of 40 units/mL heparin to the sample.

PMID- 7572798
TI  - Comparison of the kinetic fibrinogen assay with the von Clauss method and the
      clot recovery method in plasma of patients with conditions affecting fibrinogen
      coagulability.
AB  - A Kinetic Fibrinogen Assay (KFA), a method based on the kinetic reaction of the
      developing fibrin clot, was used to determine fibrinogen concentration in plasma.
      Two other methods employing different quantification principles were used for
      comparison: the von Clauss method and the procedure measuring protein
      concentration in an isolated and washed plasma clot (World Health Organization
      [WHO] method). All three methods quantified functional thrombin-coagulable
      fibrinogen. Plasma specimens were obtained from three groups of patients: those
      with liver disease and those taking either coumarin derivative or heparin. In all
      of these conditions, there are deviations from the normal process of fibrin clot
      formation. The KFA method yielded results that were consistent and provided
      excellent precision and accuracy allowing quantification of plasma fibrinogen in
      the range of 70-800 mg/dL (2-23.5 microM). The determination of fibrinogen by the
      KFA method was not adversely affected using plasma from patients treated with
      heparin and those undergoing coumarin therapy. Statistical analysis of the
      results indicated that the KFA method compared very favorably with the von Clauss
      and WHO methods. In assessing the clinical utility of each method, the WHO method
      was found to be labor intensive and time consuming; therefore, not suitable for
      routine use in a clinical laboratory. The von Clauss method required a trained
      laboratory technician and some laboratory manipulations. The KFA method was not
      only reliable and accurate, but also fully automated, making it the easiest and
      the fastest to perform routinely.

PMID- 7572801
TI  - Myoglobin in the early evaluation of acute chest pain.
AB  - Two thirds of patients hospitalized to rule out acute myocardial infarction (AMI)
      are eventually found to have a non-AMI diagnosis, whereas 2% to 8% of patients
      with AMI are inappropriately discharged from the emergency department. Myoglobin
      has been shown to increase within 2 to 3 hours of myocardial injury. This study
      evaluates the usefulness of myoglobin in acute chest pain. Serial blood samples
      were obtained from 89 suspected AMI patients evaluated in the emergency
      department. Testing included creatine kinase (CK), a creatine kinase isoenzyme
      (CK-MB), and myoglobin. Twenty five of 89 patients (28%) had a diagnosis of AMI.
      The sensitivity of myoglobin for the detection of AMI was 56% at the time of
      admission and 100% 2 hours after admission. Thirteen of 25 AMI patients (52%) had
      a positive myoglobin before increases in CK or CK-MB, including one patient
      discharged from the emergency department. More importantly, the negative
      predictive value for myoglobin at the time of admission was 83% and was 100% two
      hours after admission. This potential for 100% predictability in excluding AMI by
      the use of serial myoglobin determinations will be very helpful in the correct
      triage of patients presenting with acute chest pain.

PMID- 7572803
TI  - Laboratory and bedside evaluation of portable glucose meters.

PMID- 7572802
TI  - Evaluation of the APEC analyzer for whole blood glucose. Testing in a pediatric
      setting.
AB  - The APEC glucose analyzer (APEC, Danvers, MA) was analyzed in a pediatric
      clinical chemistry laboratory and its performance was compared with glucose
      determinations on the YSI 2300 STAT analyzer (Yellow Springs Instrument [YSI],
      Yellow Springs, OH). One hundred sixty-nine samples were simultaneously analyzed
      by the APEC and the YSI systems. The agreement between the two analyzers was
      excellent, with r = 0.986, slope = 1.04, and y intercept = -0.094. Analysis of
      the run-to-run precision yielded a CV of < or = 4.1% for both the APEC and the
      YSI instruments. Both analyzers displayed a sensitivity to at least 1.1 mmol/L
      (20 mg/dL) and both produced a linear response up to 27.8 mmol/L (500 mg/dL).
      Neither instrument was affected by icteric or hemolyzed samples. Variations in
      the patient's hematocrit did not lower the whole blood glucose values when these
      were compared with the equivalent plasma levels. In conclusion, the APEC glucose
      analyzer is suited for whole blood glucose testing in pediatric settings.

PMID- 7572804
TI  - Oxidation state of iron in hemozoin.

PMID- 7572805
TI  - Chondroid chordoma.

PMID- 7572806
TI  - Bartonella infections. Evolution from the esoteric.

PMID- 7572807
TI  - What causes fulminant hepatic failure of unknown etiology?

PMID- 7572808
TI  - Evaluation of the leukocyte differential flags on an hematologic analyzer. The
      Cobas Argos 5 Diff.
AB  - To evaluate the leukocyte differential flags of the Cobas Argos 5 Diff., the
      authors performed a comparative study between their current analyzer, the
      Technicon H2, and the manual leukocyte differential. Samples (n = 1,600) were
      collected from the Blood Disease Department of their hospital and were tested on
      both Cobas Argos 5 Diff. (ABX/Roche Hematology Division, Montpellier, France) and
      Technicon H2. Abnormalities of the manual leukocyte differential (immature
      granulocytes, blast cells, atypical lymphocytes, hyperbasophil cells,
      erythroblasts, and hairy cells) were found in 597 samples. The authors determined
      the best cut-off of the quantitative flags--atypical lymphocytes (ALYs) and large
      immature cells (LICs)--using the likelihood ratio method, and the capability of
      the 5 Diff. qualitative flags to determine abnormal subpopulations by the
      predictive value of a positive result. The presence of particular combinations of
      flags was associated with band cells and blast cells of acute lymphoblastic
      leukemia (ALL) or acute myeloblastic leukemia (AML). The sensitivity,
      specificity, and efficiency of the two analyzers were 92.1, 53.9, and 68.2,
      respectively, for the Argos 5 Diff., and 93.5, 36.7 and 57.9, respectively, for
      Technicon H2. In conclusion, the Cobas Argos 5 Diff. is well adapted for
      detecting leukocyte abnormalities.

PMID- 7572809
TI  - Evaluation of a total hematology analysis system (Sysmex HS-430). Benefits for
      large laboratories by reducing manual work load and optimizing screening efficacy
      for pathologic samples.
AB  - In this study, the authors evaluated a closed tube total hematology analysis
      system, Sysmex HS-430 (HS), which consists of two automated hematology analyzers,
      Sysmex NE-8000, the reticulocyte analyzer, Sysmex R-3000, and a slide preparation
      unit integrated in an automated sample transport system (TOA Medical Electronics,
      Kobe, Japan). The suitability of the system was compared with a conventional
      hematology system (CS) consisting of two single standing Coulter STKS analyzers
      (Hialeah, FL), one automated reticulocyte counter Sysmex R-1000, and the manual
      blood smear preparation. Evaluation was performed following the concept suggested
      by the Austrian-German societies for Clinical Chemistry and Laboratory Medicine
      that includes the evaluation of personnel supply. Eight consecutive series with a
      total of 4,896 samples were analyzed on both systems. Evaluation revealed that
      the analysis time per series was 238 minutes on the HS-430 and 359 minutes on the
      CS. The mean analyzer down times because of technical reasons were 36 minutes on
      the HS and 32 minutes on the CS. The down time because of "nontechnical" reasons
      was 31 minutes on the HS-430, but 173 minutes on the CS, which was mainly because
      of discontinuous sample loading of analyzers of the CS. The average direct
      technical time effort for complete blood cell count (CBC) analyses, reticulocyte
      counts, and blood smear preparations per series was 23 minutes on the HS and 245
      minutes on the CS. In summary, these data show that an automated system like the
      HS-430 saves 222 minutes of manual activities arising in a large routine
      hematology laboratory with a mean throughout of 612 samples per day. Furthermore,
      the system improves intralaboratory turnaround times, avoids human errors by
      automated sample identification, and guarantees more safety for laboratory staff
      by minimizing the contact with potential biohazards.

PMID- 7572810
TI  - Predicting relapse of chronic myelogenous leukemia after allogeneic bone marrow
      transplantation by bcr-abl mRNA and DNA fingerprinting.
AB  - Fourteen patients treated by allogeneic bone marrow transplantation for chronic
      myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR)
      for bcr-abl-specific transcripts. Nine patients were transplanted in the first
      chronic phase, three in the second chronic phase, and two in the accelerated
      phase. All patients achieved a complete cytogenetic and hematologic remission
      after bone marrow transplantation. Twelve patients are alive (median, 18 months;
      range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently
      detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of
      them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA
      was detectable. bcr-abl mRNA was never detectable posttransplant in three
      patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients
      8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One
      patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was
      then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never
      detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four
      patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four
      cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but
      was negative at 50 months. Three of six patients who initially had bcr-abl mRNA
      detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the
      time of development of chronic graft-versus-host disease (GVHD). These results
      suggest that the detection of subclinical Ph1 positive cells by PCR is not
      associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus
      leukemia (GVL) activity may contribute to the treatment of minimal residual
      disease in CML after allogeneic bone marrow transplantation.

PMID- 7572811
TI  - Immunohistochemical reference ranges for B lymphocytes in bone marrow biopsy
      paraffin sections.
AB  - The quantitation of B lymphocytes in paraffin-decalcified bone marrow sections is
      often used as supportive evidence of primary or residual B-cell
      lymphoproliferative disorders; however, well-defined normal ranges for B
      lymphocytes are not available. Thirty-four B5-fixed decalcified bone marrow
      sections were analyzed from a group of patients having an essentially normal bone
      marrow morphologic examination and lacking any evidence immunologic or
      hematopoietic disease. All samples were stained with CD20, CD45RA (4KB5), and
      DBA.44 for B cells, and CD45RO (UCHL-1) for T cells. Image analysis was performed
      on all cases. CD20-positive cells ranged from 0% to 5.97%. CD45RA positivity
      ranged from 0% to 5.48%. DBA.44 was positive in 0% to 2.07% of the cells. CD45RO
      positivity varied from 0% to 6.7%. These results provide useful
      immunohistochemical B-lymphocyte reference ranges in B5-fixed paraffin bone
      marrow sections.

PMID- 7572812
TI  - Occurrence and documentation of low-level bacteremia in a community hospital's
      patient population.
AB  - To document the incidence of low-level bacteremia in the patient population of
      this study, two blood culture sets were collected from symptomatic patients
      weighing more than 80 pounds. Each blood culture set consisted of a lysis
      centrifugation tube and three bottles containing different culture broths, each
      inoculated with 10 mL blood. Pathogens from 63 (26.4%) and 48 (20.1%) of the 239
      culture-positive patients were recovered from only one and two of the eight
      culture devices, respectively, representing low-level bacteremia. Isolates from
      another 60 (25.1%) of the 239 patients were recovered from all eight of the
      culture devices, representing high-level bacteremia. Whether patients had low
      level or high-level bacteremia, there were mostly insignificant differences in
      the types of species recovered, in the percentages of patients for whom therapy
      was initiated or changed following the laboratory's reports, and in the clinical
      signs, symptoms, and characteristics of the patients. Clinically documented, low
      level bacteremia is relatively common in this community hospital's patient
      population. Culturing of up to 80 mL of blood was required for detection of all
      pathogens from patients weighing more than 80 pounds.

PMID- 7572813
TI  - Detection of Bartonella (Rochalimaea) henselae bacteremia using BacT/Alert blood
      culture system.
AB  - Bartonella henselae was isolated from the blood of five febrile immunosuppressed
      patients using BacT/Alert (Organon Teknika, Durham, NC) automated microbial
      detection system. An immunofluorescence assay (using 1:1000 dilutions) was used
      to confirm identification of fastidious, pleomorphic, non-Gram staining,
      argyrophilic bacilli displaying rachety motility that had been presumptively
      identified as Bartonella spp. The practicality of identification of Bartonella
      henselae using goat antisera for use in a routine clinical microbiology
      laboratory was demonstrated by this study.

PMID- 7572815
TI  - Streptococcus anginosus, Streptococcus constellatus and Streptococcus
      intermedius. Clinical relevance, hemolytic and serologic characteristics.
AB  - A collection of 518 "Streptococcus milleri" isolates recovered from clinical
      specimens was identified to the species level according to recently established
      criteria. Streptococcus anginosus was the most frequently isolated species
      (59.3%), followed by S constellatus (30.3%) and S intermedius (10.4%). One third
      (34%) of all isolates were beta-hemolytic. The majority of S anginosus isolates
      were nonhemolytic, carried Lancefield group F, or were nongroupable. Most of the
      S constellatus isolates were beta-hemolytic, as well as 16.6% of S intermedius
      strains. Streptococcus anginosus was recovered more often from the genital and
      urinary tracts and S constellatus was recovered from the thorax. Streptococcus
      intermedius was mostly found in the head and neck area, but was also isolated
      from the abdomen and the skin, bone, and soft tissue. Streptococcus intermedius
      and nonhemolytic isolates were recovered most often from abscess-related
      specimens.

PMID- 7572814
TI  - Quantitation of HBV DNA in human serum using a branched DNA (bDNA) signal
      amplification assay.
AB  - The aim of this study was to establish the performance characteristics of a
      nonradioisotopic branched DNA (bDNA) signal amplification assay for quantitation
      of hepatitis B virus (HBV) DNA in human serum. Quantitation was determined from a
      standard curve and expressed as HBV DNA equivalents/mL (Eq/mL; 285,000 Eq = 1 pg
      of double stranded HBV DNA). The bDNA assay exhibited a nearly four log dynamic
      range of quantitation and an analytical detection limit of approximately 100,000
      Eq/mL. To ensure a specificity of 99.7%, the quantitation limit was set at
      700,000 Eq/mL. The interassay percent coefficient of variance for quantification
      values ranged from 10% to 15% when performed by novice users with different sets
      of reagents. Using the bDNA assay, HBV DNA was detected in 94% to 100% of
      hepatitis B e antigen-positive specimens and 27% to 31% of hepatitis B e antigen
      negative specimens from chronic HBV-infected patients. The bDNA assay may be
      useful as a prognostic and therapy monitoring tool for the management of HBV
      infected patients undergoing antiviral treatment.

PMID- 7572816
TI  - Impact of variation in endocervical specimen collection and testing techniques on
      frequency of false-positive and false-negative Chlamydia detection results.
AB  - Rapid tests for detection of Chlamydia trachomatis are considerably more likely
      to provide accurate, reliable results if high quality endocervical specimens
      containing large quantities of the pathogen are submitted for testing, and if
      laboratories routinely detect and confirm Chlamydia at levels below the test
      manufacturer's recommended cut-off using previously published, well-documented
      guidelines that have been verified by in-house testing. Routine or periodic
      microscopic analysis of endocervical specimen quality may be necessary both to
      ensure the adequacy of specimens and to help motivate personnel performing the
      specimen collection procedures. False-positive test results can be significantly
      reduced or eliminated by confirming positive results with the use of an
      independent assay. Clinical laboratories currently have the opportunity to
      substantially improve both the sensitivity and the specificity of many currently
      available rapid assays for the detection of Chlamydia trachomatis.

PMID- 7572817
TI  - Prospective peer review in surgical pathology.
AB  - Quality assurance (QA) in surgical pathology has focused primarily on
      retrospective audits of randomly selected cases. The authors describe an
      effective method of prospective audit for a selected class of surgical specimens-
      diagnostic biopsies--and document the benefits, additional staff time required
      and impact on turnaround time. Additionally, these results were compared with a
      retrospective review. During a 6-month period, all diagnostic surgical pathology
      biopsies (n = 2,694, 55% of all cases) were reviewed by a second pathologist
      before release of the final report. Errors detected were subdivided into four
      categories: (1) major: errors in diagnosis that could directly affect patient
      care; (2) diagnostic discrepancies: errors in diagnosis that should not affect
      patient care; (3) minor: correct diagnosis rendered, but report correction
      required to add supportive information; (4) clerical: typographical and
      grammatical errors. Thirty-two major errors were found, involving 1.2% of cases
      reviewed. This manner of review caused an increase in overall turnaround time
      from 1.62 days to 1.79 days, and an increase in turnaround time for diagnostic
      biopsies from 1.44 days to 1.50 days. Time spent in performing prospective peer
      review averaged 4 hours per day. For comparison, results were included from a
      retrospective review performed on 480 of the 5,556 cases accessioned in a 6-month
      period before the institution of prospective quality assurance. This
      retrospective review revealed eight major errors (1.7%). In conclusion, the
      prospective peer review of diagnostic biopsies yields sufficient benefits in
      increased accuracy of diagnostic reports to justify the slight increase in
      additional work by pathologists.

PMID- 7572818
TI  - Histologic spectrum of cryptogenic chronic liver disease and comparison with
      chronic autoimmune and chronic type C hepatitis.
AB  - Most histologic studies of cryptogenic chronic liver disease were done before the
      discovery of hepatitis C, and therefore encompass the histologic spectrum of this
      disease. The authors report the histopathologic findings of 18 liver biopsies of
      presumed cryptogenic chronic liver disease patients and compared them to chronic
      autoimmune hepatitis and hepatitis C virus biopsies. Severe bridging fibrosis or
      cirrhosis was present in 55%. Eighty percent of biopsies had minimal
      necroinflammatory activity including those with cirrhosis; 20% had moderate
      activity. Histologic distinction from chronic hepatitis C was difficult in the
      minimally active cryptogenic chronic liver disease biopsies because 20% of
      biopsies had portal lymphoid follicles and 33% had macrovesicular steatosis.
      Chronic autoimmune hepatitis had more parenchymal necroinflammatory activity and
      plasma cells than did either cryptogenic chronic liver disease or chronic
      hepatitis C biopsies. These findings suggest that one form of cryptogenic chronic
      liver disease is a persistent, low grade hepatitis that can progress to cirrhosis
      despite an innocuous histopathologic appearance. Pathologists should be aware
      that cryptogenic chronic liver disease biopsies may have minimal histologic
      abnormalities. These biopsies should not be reported as normal. Such cases
      require long-term clinical follow-up.

PMID- 7572819
TI  - Atypical glandular cells of undetermined significance. Cytologic criteria to
      separate clinically significant from benign lesions.
AB  - Histologic follow-up of the cervical-vaginal smear diagnosis of atypical
      glandular cells of undetermined significance (AGUS) shows a broad spectrum of
      clinically significant (preneoplastic or neoplastic) and benign lesions. There
      are few statistical studies that have attempted to separate these AGUS categories
      based on select cytologic criteria. The authors retrospectively reviewed 116 AGUS
      without concurrent squamous dysplasia smears (66 clinically significant and 50
      benign lesions), and used logistic regression analysis to identify the cytologic
      criteria of irregular nuclear membranes, atypical single cells, and decreased
      cytoplasm as useful in separating clinically significant from benign lesions.
      Using contingency tables, these criteria in combination had a sensitivity 29% and
      a specificity of 94% in the diagnosis of clinically significant lesions. If any
      single criterion was present, the sensitivity and specificity were 100% and 28%,
      respectively. In conclusion, by using key cytologic criteria, a percentage of
      benign AGUS lesions can be separated from clinically significant AGUS lesions.

PMID- 7572821
TI  - Detection of hepatitis B and hepatitis C viral sequences in fulminant hepatic
      failure of unknown etiology.
AB  - In a significant number of patients, the etiology of fulminant hepatic failure
      (FHF) is unknown. To determine whether hepatitis B virus (HBV) and hepatitis C
      virus (HCV) play a role in patients without serologic markers of HBV and HCV
      infection, the authors examined tissue samples from 15 liver explants with
      massive hepatic necrosis for the presence of viral sequences by the polymerase
      chain reaction (PCR). The specimens were derived from nine patients with FHF of
      unknown etiology; two with serum hepatitis B surface antigen (HBsAg); two with
      antibodies to HCV; one with antibodies to hepatitis A virus (HAV) and anti-HBc of
      the IgM class; and one with isoniazid toxicity. Nucleic acids were extracted from
      frozen liver samples. RNA was used as a template for reverse transcription,
      followed by double PCR with nested primers for the 5'-untranslated region of HCV.
      DNA was tested by single PCR for S gene sequences of HBV. Hepatitis B virus
      sequences were detected in the specimens of the two HBsAg positive patients, the
      anti-HAV/anti-HBc positive patient, and three of nine patients with FHF of
      unknown etiology. Hepatitis C virus sequences were present in the explant of one
      patient with FHF of unknown etiology, but not in the two patients with antibodies
      to HCV. In two specimens with molecular findings of HBV infection (1 from a
      patient with serum HBsAg and 1 without), there was immunohistochemical evidence
      of coinfection or superinfection with hepatitis delta virus (HDV). In conclusion,
      in this patient population, HBV, alone or with HDV or HAV, causes fulminant
      hepatic failure more often than HCV infection. However, in the majority of
      patients, the etiology of fulminant hepatic failure remains unknown.

PMID- 7572822
TI  - Primary basaloid squamous cell carcinoma of the trachea.
AB  - Basaloid squamous cell carcinoma (BSCC) is an unusual but well-established
      entity, primarily in the upper aerodigestive tract, composed of basaloid cells
      associated with dysplastic to neoplastic squamous cells, and characterized by an
      aggressive and rapidly fatal course. To date, BSCC originating in the trachea has
      not been reported. In this article, the authors describe the clinical, gross, and
      microscopic pathologic, histochemical, and immunohistochemical features of two
      cases of BSCC arising in the trachea. Features distinguishing this entity from
      other, more common tumors of the trachea, including metastases and direct
      extension from other sites of origin, are also discussed.

PMID- 7572820
TI  - Percutaneous ultrasound-guided needle biopsy of hepatic mass lesions using a
      cytohistologic approach. Comparison of two needle types.
AB  - This study compared the ability to diagnose and accurately classify hepatic mass
      lesions by ultrasound-guided biopsy using two different needle types: a 20 gauge
      needle that yielded primarily cytologic material and an 18 gauge automated core
      biopsy needle. Slides prepared from each of the needle types were separately
      evaluated in a blinded fashion. The 20 gauge needle had a sensitivity of 90%, a
      specificity of 90%, and enabled exact tumor classification in 70% of cases. The
      18 gauge core biopsy had a sensitivity of 85%, a specificity of 100%, and allowed
      exact tumor typing in 82% of cases. The sensitivity and specificity of both
      needle types combined was 98% and 100%, respectively, and all malignancies were
      correctly typed. A combined cytohistologic approach provides a highly accurate
      means of diagnosing and typing hepatic tumors and provides a suitable sample for
      confirmatory stains. Accurate tumor typing may affect therapeutic decisions.

PMID- 7572823
TI  - Distribution of iron in the liver.

PMID- 7572824
TI  - Interpretation of bronchial brush specimens.

PMID- 7572825
TI  - A preventive, psychoeducational approach to increase perceived social support.
AB  - Investigated the effects of a 13-week preventive, psychoeducational intervention
      program to improve perceived social support. Fifty-one, low-perceived support,
      community residents were randomly assigned to an intervention or wait-list
      control condition. Intervention subjects received training in social skills and
      cognitive reframing regarding the self and social relations. The intervention led
      to increased perceived social support from family, but not from friends. As
      hypothesized by social cognition models, increases in perceived support appeared
      to be mediated by changes in self-esteem and frequency of self-reinforcement.
      Further, such changes in cognition about the self were larger than the changes
      observed for perceived support, suggesting that it may be easier to change
      cognition about the self than perceptions of support.

PMID- 7572826
TI  - Impact of the JOBS intervention on unemployed workers varying in risk for
      depression.
AB  - Reports the results of the JOBS II randomized field experiment that included a
      sample of 1,801 recent job losers, 671 of which participated in a modified
      version of the JOBS I intervention for unemployed workers (Caplan, Vinokur,
      Price, & van Ryn, 1989). The intervention focused on enhancing the sense of
      mastery through the acquisition of job-search and problem-solving skills, and on
      inoculation against setbacks. JOBS II was intended to prevent poor mental health
      and to promote high quality reemployment. The study tested whether the efficacy
      of the intervention could be increased by screening and oversampling respondents
      who were at higher risk for a significant increase in depressive symptoms.
      Results demonstrated that the intervention primarily benefited the reemployment
      and mental health outcomes of the high-risk respondents. This suggests the
      feasibility of enhancing the efficacy of this preventive intervention by
      targeting it for high-risk unemployed workers who could be identified
      prospectively.

PMID- 7572828
TI  - Occupational conditions and workers' sense of community: variations by gender and
      race.
AB  - The literature is reviewed to define a sense of community in the workplace and to
      identify factors that may foster it. A model is developed and estimated with
      survey data from a culturally diverse sample of men and women performing lower
      level jobs at a medium-sized manufacturing firm. Results of regression analyses
      are reported that correct for sample selection bias resulting from the lower
      response rates of minority workers. Findings suggest that well-designed jobs and
      supportive workplace relationships and policies are important in explaining
      workers' sense of community, defined as workers' perceptions of mutual commitment
      between employee and employer. Informal sources of support play a larger role in
      explaining men's sense of community, while formal sources of support are more
      important in explaining women's sense of community. Findings further suggest that
      African American workers, especially women, have a difficult time experiencing a
      sense of community at work.

PMID- 7572827
TI  - Oral contraceptive use among African American adolescents: individual and
      community influences.
AB  - Side effects of oral contraceptives are a noteworthy problem, particularly among
      low-income young women who reside in inner-city communities. The problem may be
      compounded by inadequate family planning services, particularly when such
      services are provided by general medical practices with high volumes of clients.
      This study examined the prevalence and correlates of pill-related side effects,
      with particular attention to the role of clinic characteristics. Participants
      were 177 pregnant and parenting African American adolescents and young women
      (average age = 18.34). The experience of a pill-related side effect was the most
      frequently cited barrier to birth control use, and it was significantly related
      to contraceptive behavior. Finally, although participants attending comprehensive
      clinics experienced more barriers to medical service use than those attending
      neighborhood clinics, they reported fewer problems with pill-related side effects
      and better psychological functioning. Implications for future research and policy
      are discussed.

PMID- 7572829
TI  - Teacher and parent perceptions of behavior problems among a sample of African
      American, Hispanic, and non-Hispanic white students.
AB  - A multiracial/multiethnic sample of middle school adolescents and their teachers
      was used to assess whether teacher ratings of student behavior problems varied
      according to teacher-student racial/ethnic differences and students' perception
      of teachers' attitudes toward them. No significant mean score differences were
      found for Hispanic or non-Hispanic white students according to the race/ethnicity
      of the teachers doing the ratings. However, African American students rated by
      Hispanic and non-Hispanic white teachers had significantly higher mean total
      behavior problem scores than African American students rated by African American
      teachers. Teacher ratings were also compared to those made by parents. The
      percentage of students rated as cases by teachers but not by parents differed
      significantly by race/ethnicity of student. Other findings indicated highly
      significant relationships between student-perceived teacher disparagement and the
      assignment of high behavior problem scores to students by teachers.

PMID- 7572830
TI  - Prevention of depression with primary care patients: a randomized controlled
      trial.
AB  - The prevention of major depression is an important research goal which deserves
      increased attention. Depressive symptoms and disorders are particularly common in
      primary care patients and have a negative impact on functioning and well-being
      comparable with other major chronic medical conditions. The San Francisco
      Depression Prevention Research project conducted a randomized, controlled,
      prevention trial to demonstrate the feasibility of implementing such research in
      a public sector setting serving low-income, predominantly minority individuals:
      150 primary care patients free from depression or other major mental disorders
      were randomized to an experimental cognitive-behavioral intervention or to a
      control condition. The experimental intervention group reported a significantly
      greater reduction in depressive levels. Decline in depressive levels was
      significantly mediated by decline in the frequency of negative conditions. Group
      differences in the number of new episodes (incidence) of major depression did not
      reach significance during the 1-year trial. We conclude that depression
      prevention trials in public sector primary care settings are feasible, and that
      depressive symptoms can be reduced even in low-income, minority populations. To
      conduct randomized prevention trials that can test effects on incidence with
      sufficient statistical power, subgroups at greater imminent risk have to be
      identified.

PMID- 7572831
TI  - Evaluation of a preventive intervention for a self-selected subpopulation of
      children.
AB  - Evaluated an experimental preventive intervention developed for children who
      perceived their parents as problem drinkers. The 8-session program was designed
      to improve children's coping, self-esteem, and social competence, and modify
      alcohol expectancies which were specified as mediators of the effects of parental
      alcohol abuse on child mental health. Participants were 271 self-selected 4th-,
      5th-, and 6th-grade students in 13 schools. The children were randomly assigned
      to treatment or delayed treatment conditions and the program was given to three
      successive cohorts of students. A meta-analysis across three different cohorts
      indicated significant program effects to improve knowledge of the program content
      and the use of support- and emotion-focused coping behaviors for the full sample.
      A slightly stronger range of effects was found for a high-risk subsample.

PMID- 7572832
TI  - The role of work experience and individual beliefs in police officers'
      perceptions of date rape: an integration of quantitative and qualitative methods.
AB  - Surveyed police officers from two police departments in the Midwest on their
      perceptions of date rape (N = 91). The aim of this research was to examine the
      influence of officers' work experiences and general beliefs about women on their
      perceptions of date rape. Two approaches were utilized. First, using quantitative
      structural-equation modeling, a model that integrated work experiences and
      individual beliefs was evaluated using LISREL VII. Results suggest a direct path
      from the work experience variables to perceptions of date rape: Officers with
      more experience with rape cases held more sympathetic beliefs about date rape and
      date rape victims. Officers who found their training on rape to be very helpful,
      and those who reported that their work environment was sexualized and sexual
      harassment was a problem, were also less victim blaming. An indirect influence of
      these variables was also supported. Officers with more experience, those who
      perceived their training as helpful, and those with heightened awareness of
      sexual harassment in the workplace also held more favorable attitudes toward
      women, which, in turn, predicted less victim-blaming perceptions of date rape.
      Second, qualitative methods were used to have the police define and describe in
      their own words what has shaped their beliefs about date rape. These narratives
      were content analyzed by two raters. The qualitative results validated the
      quantitative findings as the officers were most likely to mention professional
      experience with rape cases and departmental trainings as important factors that
      changed their opinions. Work climate and personal experiences were also cited as
      influential. Implications for integrating qualitative and quantitative methods in
      research, and training interventions with police are discussed.

PMID- 7572833
TI  - Negative social interactions, distress, and depression among those caring for a
      seriously and persistently mentally ill relative.
AB  - Investigated both positive and negative social interactions and their effect on
      mental health for 106 individuals caring for a seriously mentally ill family
      member. Results from mixed-model (hierarchial and stepwise) multiple regression
      analyses in which caregiver age, socioeconomic status, caregiving demand, and
      severity of patient symptoms was controlled showed that negative social
      interaction accounted for a significant portion of variance in the caregivers'
      feelings of distress and depression. Moderated multiple regression analyses
      showed that under conditions of high negative interaction, the relationship
      between demand and distress was intensified. Implications of these findings for
      the conceptualization and measurement of negative social interaction as well as
      its clinical implications were discussed.

PMID- 7572835
TI  - Adolescent suicidal behaviors as a function of depression, hopelessness, alcohol
      use, and social support: a longitudinal investigation.
AB  - Surveyed two high school cohorts (ns = 698 and 283) to study independent,
      prospective predictors of adolescent suicidal behaviors (thoughts, communication
      to others, attempts). Within each cohort, there were two measurements conducted 6
      months apart. Structural equation models were tested, with depressive symptoms,
      hopelessness, alcohol consumption, social support, and gender serving as
      predictors. In the larger cohort, depression predicted later levels of all three
      suicidal behaviors controlling for baseline suicidal behaviors. Also, suicidal
      thoughts predicted later communications, and suicide attempts predicted future
      thoughts. In the smaller cohort, alcohol consumption predicted all three suicidal
      behaviors at the later measurement, whereas depression was predictive only of
      later thoughts. Major issues regarding prevention, theories of suicide and
      negative affect, and methodological/analytical approaches were discussed.

PMID- 7572836
TI  - Development and validation of adolescent-perceived microsystem scales: social
      support, daily hassles, and involvement.
AB  - Developed and validated instruments for urban and culturally diverse adolescents
      to assess their self-reported transactions with family, peer, school, and
      neighborhood microsystems for the constructs of social support, daily hassles,
      and involvement. The sample of 998 youth were from schools in three Eastern
      cities with high percentages of economically disadvantaged youth. Data were
      collected before and after the transition to junior high school or to senior high
      school. Blacks constituted 26%, whites 26%, and Latinos 37% of the sample. Factor
      analyses confirmed and enhanced the hypothesized four-factor microsystem factor
      structure for support, hassles, and involvement; internal consistency and
      stability coefficients were consistent with these structures. In general, the
      microsystem factors were common across gender, ethnicity, and age. However, when
      group differences did occur on these demographic variables, they tended to
      validate the salience of microsystem specificity. In contrast to the total
      scores, the microsystem-specific factors yielded more meaningful and differential
      information with regard to demographic differences and the mediating processes
      across a school transition.

PMID- 7572837
TI  - Social support processes in early childhood friendship: a comparative study of
      ecological congruences in enacted support.
AB  - Examined congruences between children's friendships and classroom social
      ecologies in three distinct settings, and poses that such congruences or social
      adaptations are aptly characterized as a process of enacted social support; i.e.,
      an interpersonal transaction involving the reduction of evasion of stress. Data
      were derived from Corsaro's recent ethnographics of children's friendship and
      peer culture in a University Preschool (Corsaro, 1985) and Head Start center
      (Corsaro, 1994), and from Rizzo's (1989) ethnography of friendship development
      among first-grade children. Despite vast differences across settings, the nature
      and activities of children's friendships appeared consistently linked with
      specific organizational features in their life-worlds and in this way may
      constitute significant interpersonal and individual adaptations to that world. In
      this view, friendship is best seen not as a static entity, which children
      appropriate in a consistent fashion, but as a general and malleable concept,
      which they modify and use in a collaborative fashion to address shared
      psychosocial concerns. Findings are related to research on the link between
      perceived and enacted support, and on the interplay between relational and social
      support processes.

PMID- 7572834
TI  - Protective processes in adolescence: matching stressors with social resources.
AB  - Working within the "matching theory" of social supports, this research focuses on
      depressed mood and examines how resilience to stress during adolescence is shaped
      by developmental constraints on the use of support for coping with problems in
      the family, peer, and personal arenas. The sample is 1,036 adolescents
      systematically drawn from 3 community high schools in the Boston area.
      Predictions center on the efficacy of peer and family supports, and two
      intraindividual protective factors: sense of mastery and sense of social
      integration. Findings indicate little evidence of cross-domain stress buffering
      (where family support buffers the effects of peer stress on mood, and vice
      versa), suggesting that family and peer domains are more distinct during this
      stage of development. Protective effects for friendship stresses are evidenced,
      but boys are more able than girls to marshal their personal and support resources
      in managing friendship problems. Discussion centers on matching theory and the
      role of development in shaping coping responses to stress.

PMID- 7572838
TI  - Alternative influences on children's development of friendships: a social
      developmental perspective.

PMID- 7572839
TI  - Comment on study of nasal respiratory resistance.

PMID- 7572840
TI  - Response to comment on TMD.

PMID- 7572841
TI  - Angle bound orthodontics.

PMID- 7572842
TI  - Viewpoint: change for the better.

PMID- 7572843
TI  - Current status of graduate orthodontic training.

PMID- 7572844
TI  - Why belong to the AAO.

PMID- 7572845
TI  - Treatment of Class II malocclusions with the Jasper Jumper appliance--a
      preliminary report.
AB  - The effect of the Jasper Jumper appliance (American Orthodontics, Sheboygan,
      Wis.) on the dentofacial complex was studied in 17 consecutive growing patients
      who had Class II, Division 1 malocclusions. Lateral cephalograms taken before
      treatment and immediately after removal of the Jumpers were analyzed according to
      the method of Pancherz. The following results were found: (1) Class I occlusal
      relationships were achieved in all patients in an average treatment time of 6
      months. (2) The correction of the Class II malocclusion was a result of skeletal
      (40%) and dental (60%) changes. (3) Skeletal Class II correction was
      predominantly restricted to the mandible. (4) The dentoalveolar part of total
      molar relationship correction took place to the same extent in both jaws, whereas
      in overjet correction the maxillary dental changes outweighed the mandibular
      changes by far. (5) When compared with normal growth changes (Bolton standards),
      treatment with Jasper Jumpers distalizes the upper dentition and moves the lower
      teeth mesially. Mandibular growth seems to be increased to some extent. It was
      concluded that treatment with the Jasper Jumper appliance presents an effective
      method to correct Class II malocclusion in growing patients.

PMID- 7572846
TI  - Microbial attachment on orthodontic appliances: I. Wettability and early pellicle
      formation on bracket materials.
AB  - The objectives of this study were to investigate the wettability of orthodontic
      bracket material surfaces and the composition of salivary films adsorbed onto
      them after 30 and 60 minutes in vivo exposure. Specimens from stainless steel,
      fiber-reinforced polycarbonate, and polycrystalline alumina bracket manufacturing
      raw materials were subjected to (a) contact angle measurements with a homologous
      series of liquids, (b) micro multiple internal reflection Fourier transform
      infrared spectroscopy (microMIR FTIR) for the characterization of the molecular
      composition of the in vivo adsorbed groups, and (c) incident light optical
      microscopy of the acquired films. The highest critical surface tension was
      obtained from stainless steel (40.8 +/- 0.4 dynes/cm) followed by polycarbonate
      (32.8 +/- 1.3 dynes/cm) and alumina (29.0 +/- 0.9 dynes/cm), suggesting a higher
      potential for increased plaque-retaining capacity for the stainless steel
      brackets. Accordingly, the total work of adhesion and its polar and nonpolar
      components were consistent with the surface tension ranking. The nonpolar
      component of the work of adhesion was higher than its polar counterpart for all
      materials tested, implying a possible higher attachment prevalence for those
      microorganisms using dispersive forces, such as van der Waals forces, as the
      predominant attachment mechanism to surfaces. Qualitative and quantitative
      variations were observed in the adsorbed films after 30 and 60 minutes intraoral
      exposure that may reflect the influence of the surface properties of these
      substrates on the structure of the pellicle formed in vivo.

PMID- 7572847
TI  - Influence of indomethacin on bone turnover related to orthodontic tooth movement
      in miniature pigs.
AB  - The purpose was to evaluate the influence of a prostaglandin inhibitor,
      indomethacin, on the tissue reaction related to orthodontic tooth movement.
      Sixteen miniature pigs were chosen for the study, eight of which received
      indomethacin perorally every day of the 39-day observation period. Sentalloy
      expansion springs (GAC, Central Islip, N.Y.) delivering 100 cN were inserted on a
      segmented arch between the central lower incisors. Intravital labeling with
      tetracycline was used for the evaluation of the rate of bone formation. After the
      pigs were killed, the bone turnover was evaluated on undecalcified methacrylate
      embedded sections and on microradiographs. The histomorphometric analysis of bone
      turnover revealed that the relative extent of resorption surfaces was decreased
      significantly in the indomethacin treated animals. Formation surfaces were also
      decreased although not significantly. The bone turnover, but not the
      mineralization rate, was influenced. The results corroborate the recommendation
      that prostaglandin inhibitors should be avoided during orthodontic treatments.

PMID- 7572848
TI  - Changes in mandibular rotation after muscular resection. Experimental study in
      rats.
AB  - The purpose of this study was to evaluate the effect of bilateral muscular
      resection on the rotational pattern of the rat mandible. The specific aim of the
      study was to seek possible changes in "articular growth" in the posterior (ramus
      and condyle of the mandible), and in the anterior part of the face (upper
      viscerocranium, and maxillary and mandibular dentoalveolar processes). The
      masseter, temporal, and suprahyoid muscles were bilaterally resected in three
      experimental groups of 21-day-old female Wistar rats. Another group of rats
      served as control. The results were evaluated at 42 (prepubertal) and 60 days
      after birth (pubertal rats). The craniofacial growth pattern, ramus dimension,
      condylar growth direction, histologic evaluation of condylar cartilage, and
      dentoalveolar processes height changes were studied. Two mandibular rotational
      patterns were found: one inferior after masseter muscles resection (MR), and the
      other superior after temporal muscles resection (TR). A less intense superior
      rotational pattern, after suprahyoid muscles resection (SR), was found also.
      Morphologic changes were more intense in older rats. On the contrary, more
      intense condylar histologic changes were found in younger rats. Changes in
      "articular growth" primarily take place at maxillary and mandibular dentoalveolar
      processes. Condylar growth amount could be modified to a limited extent. More
      important were the changes in condylar growth direction. An upward rotational
      pattern of the upper viscerocranium was detected when the inferior mandibular
      rotation pattern was produced.

PMID- 7572849
TI  - The effects of exogenous prostaglandins on orthodontic tooth movement in rats.
AB  - The long-term effects of varying concentrations and frequencies of injectable,
      exogenous prostaglandin E2 (PGE2) on the rate of tooth movement and the amount of
      root resorption were evaluated. There were 132 male Sprague-Dawley rats 8 weeks
      old that initially weighed 225 to 250 gm. Five animals were in a pilot study,
      while seven were baseline controls and eight were appliance controls. The
      remaining 112 animals were divided into two experimental time periods of 2 and 4
      weeks. Then, each experimental time period was divided into four subgroups of 14
      animals based on concentration levels of PGE2 injections, i.e., 0.1, 1.0, 5.0 and
      10.0 micrograms. Half of these animals in the dosage subgroup received a single
      injection at appliance placement and the other half received weekly injections. A
      fixed orthodontic appliance consisting of closed-coil nickel-titanium springs
      were ligated between the maxillary incisors and maxillary first molars. The
      initial activating force was 60 gm. The results showed that injections of
      exogenous PGE2 over an extended period of time in rats did enhance the amount of
      orthodontic tooth movement. However, there was no statistically significant
      difference in tooth movement between the single and multiple injection groups or
      among the four concentration levels of PGE2 used in either the 2- or 4-week time
      periods. The amount of root resorption as seen from scanning electron micrographs
      did increase with the use of prostaglandin injections, specifically with
      increased numbers of injections and with increased concentrations of PGE2.

PMID- 7572851
TI  - Equilibrium clarified.
AB  - Understanding the concept of equilibrium is crucial to understanding the
      mechanics of tooth movement. The purpose of this article is to clarify the
      concept of equilibrium. This concept is most clearly understood when the
      clinician focuses on the appliance. Understanding the forces acting to deform the
      appliance readily translates to knowledge of the forces acting on the teeth.
      Knowing the forces that act on the teeth allows the clinician to predict tooth
      movement more accurately.

PMID- 7572853
TI  - Scanning electron microscopic study and shear bond strength measurement with 5%
      and 37% phosphoric acid.
AB  - Direct bonding of orthodontic attachments has become a clinical reality with the
      application of the acid etch technique, using 37% phosphoric acid. The objective
      of this study was to detect the etch pattern with scanning electron microscopy
      and the shear bond strength with a Hounsefield tensometer (Nene Instruments Ltd.,
      Northampton, England) by using 37% and 5% phosphoric acid (H3PO4). It was
      observed that with 5% H3PO4 there was minimal enamel loss compared with 37%
      H3PO4. There was no significant difference in shear bond strength, when enamel
      surface was etched with 5% H3PO4 and 37% H3PO4.

PMID- 7572850
TI  - Changes in facial dimensions assessed from lateral and frontal photographs. Part
      I--Methodology.
AB  - The purpose of this study was to evaluate the changes in facial dimensions
      between 4 and 13 years of age and to provide normative standards that can be used
      for comparative purposes. The measurements were obtained from serial frontal and
      lateral photographs available on 20 subjects; 10 boys and 10 girls. The
      photographs were digitized and displayed on a computer monitor. Thirty-two
      landmarks were identified and 29 linear dimensions were measured. Analysis of
      variance was used to compare boys and girls and the repeated measure analysis
      (ANOVA) was used to evaluate the changes with age. From the findings, the
      conclusions were made as follows: (1) Proportionately, the total length of the
      face increased at a rate about two times that of the width of the face. (2) The
      changes in the dimensions of the eyes were the most stable of all the parameters
      measured. (3) There was a greater degree of variability in parameters directly
      affected by variations in facial growth patterns, e.g., chin prominence. The
      standard deviation was several times greater than the average increment of
      change. (4) The rates of growth for the vertical length and sagittal depth of the
      nose were twice as much as the rate of increase for the lateral width of the
      nose. (5) The incremental changes in the size of the lips were the most variable,
      but the total change in the vermillion length was the smallest of all the
      parameters measured. The standardized photographs from which the present
      measurements were obtained provide a unique opportunity to study facial growth
      and provides an accurate description of facial changes.

PMID- 7572854
TI  - How to deal with the drop-out in clinical follow-up studies: results of a long
      term follow-up study of orthodontically treated patients.
AB  - The drop-out in a long-term follow-up study of former orthodontically treated
      patients was analyzed to avoid biased results. Since structural conformity of the
      responders (n = 299) and the potential study population (n = 1464) cannot be
      presumed on the basis of the clinical results, roentgenologic results, and
      questionnaires, analysis of the participating patients, the follow-up method was
      used. By means of questionnaires sent to all nonresponders, a comparison of
      responding and nonresponding patient characteristics was completed to find a
      presumed selectivity bias. The comparison of the participating patients (n = 299)
      and the total sample revealed that the responders live closer to the health
      center, had a longer treatment time, and a shorter posttreatment interval.
      Compared with nonresponders (n = 266), the responders were satisfied with the
      treatment result and had a higher dental Intelligence Quotient (IQ, concerning
      tooth and jaw position). Although a definite answer to the question of validity
      of the examined subsample was difficult to give, the description and evaluation
      of the parameters that might be reasons for missing at random respectively, not
      missing at random was recommended.

PMID- 7572852
TI  - A new experimental model for studying the response of periodontal ligament cells
      to hydrostatic pressure.
AB  - An apparatus was developed to apply positive or negative hydrostatic pressure
      dynamically to periodontal ligament (PDL) cells in vitro. The objective of this
      investigation was to construct this apparatus and to determine its effects on PDL
      cells. Human PDL cells were collected from freshly extracted premolars. At the
      sixth passage, the cells were mechanically stimulated by this apparatus at
      different magnitudes of continuous positive or negative hydrostatic pressures
      (PHP or NHP, respectively). The application of PHP between 0.3 and 30 gm/cm2
      significantly enhanced prostaglandin E (PGE) production and intracellular cyclic
      AMP (cAMP) of the cells. In contrast, perturbation by NHP significantly decreased
      PGE production and intracellular level of cAMP. Proliferation rate increased
      significantly at 24 and 48 hours due to stimulation of these cells with -30
      gm/cm2 of NHP. Challenging these cells with +30 gm/cm2 of PHP significantly
      decreased the proliferation rate of these cells at 24 and 48 hours. Stimulation
      by PHP between +30 to +600 gm/cm2 increased cell length and width and appeared to
      increase surface area attachment to the bottom of the culture dishes. In
      contrast, NHP (between -30 and -600 gm/cm2) decreased these dimensions and
      appeared to reduce the surface area of attachment. These results indicate that
      this type of mechanical perturbation of PDL cells produces physiologic responses
      and is not detrimental to their vitality.

PMID- 7572856
TI  - A possible mechanism of action of repelling, molar distalizing magnets. Part I.
AB  - The magnetic component of certain time-varying inductive electromagnetic fields
      may be a large contributor to the accelerated osteogenic rate in nonunion
      fracture repair. Evidence is also accumulating to demonstrate that certain static
      magnetic fields may stimulate osteogenesis in in vitro and in vivo research, as
      well as orthopedic clinical application. We, therefore, hypothesize that static
      magnetic fields in orthodontics generate simultaneous force fields and bioeffects
      that may account for the observed benefits.

PMID- 7572857
TI  - Vertical dimension and therapeutic choices.
AB  - The vertical skeletal pattern is a factor that makes malocclusions with the same
      tooth arrangement very different. A sample of 323 patient records was examined to
      observe variations in vertical dimension. The sample was divided into essentially
      three groups. The differences most commonly encountered during the treatment of
      the three groups are described and illustrated with brief case reports of
      patients representative of each of the three groups.

PMID- 7572858
TI  - Holograms in orthodontics: a universal system for the production, development,
      and illumination of holograms for the storage and analysis of dental casts.

PMID- 7572855
TI  - Correction of a severe Class II malocclusion that required a two-stage
      orthognathic procedure: a case report.
AB  - The treatment of this patient, who had been severely compromised with prior
      orthodontics, was successful because the tooth movement and the surgical
      procedures were carefully planned and coordinated. This case report illustrates
      the concept that facial balance and harmony is related (1) to an acceptable
      skeletal pattern and (2) to teeth that are properly positioned within their bony
      support.

PMID- 7572860
TI  - A comparison of blood lipid and lipoprotein values in young adults who die
      suddenly and unexpectedly from atherosclerotic coronary artery disease with other
      noncardiac deaths.
AB  - Postmortem blood lipid and lipoprotein analyses were conducted in a case
      controlled study of young adults (ages 22-43) who died suddenly and unexpectedly
      of atherosclerotic coronary artery disease in Allegheny County, Pennsylvania.
      None of the individuals in the study group (n = 28 cases) had a significant
      medical or cardiac history except in the immediate antemortem period. The control
      group (n = 31) consisted of age- and sex-matched cohorts who died of noncardiac
      related fatalities and who had no evidence of CAD. The results indicated a male
      to-female ratio of nearly 30:1 with a marked predominance of young white men.
      Mean total cholesterol (241 mg/dL), triglycerides (583 mg/dL), and low-density
      lipoproteins (LDL) (107 mg/dL) were all significantly elevated in the study group
      as compared to controls (p < 0.001, p < 0.018, and p < 0.001 for the three
      parameters, respectively). Mean Apolipoprotein B (98.7 mg/dL) was also
      significantly elevated compared to control values (p < 0.001). By contrast, mean
      high-density lipoprotein values (36 mg/dL) were not significantly different from
      control values (p = 0.35), and mean values of Apolipoproteins A1 (121 mg/dL) and
      A2 (37.6 mg/dL) were essentially identical to control values (p = 0.44 and p =
      0.64, respectively). The differences in these biochemical markers between the two
      groups could not be explained by differences in postmortem interval or by the
      presence of recently ingested food. These findings indicate that elevations of
      plasma cholesterol, triglycerides, LDL, and Apolipoprotein B are important
      biochemical markers for the development of early and apparently clinically silent
      yet life-threatening coronary artery disease.

PMID- 7572859
TI  - Can a learned treatise support substandard care?

PMID- 7572861
TI  - Homicidal blunt head trauma, diffuse axonal injury, alcoholic intoxication, and
      cardiorespiratory arrest: a case report of a forensic syndrome of acute brainstem
      dysfunction.
AB  - Sudden death can occur in drunk individuals who are severely beaten about the
      face. The structural basis for this forensic syndrome is unknown. We herein
      describe the case of an intoxicated 23-year-old man (blood alcohol 234 mg%, 51
      mmol/l) who was involved in an altercation and received blows and kicks to his
      head. A cardiorespiratory arrest occurred during the assault. He was resuscitated
      in hospital 23 min later but died 90 h after admission of severe ischemic
      encephalopathy and bronchopneumonia. Postmortem examination revealed diffuse
      scalp bruising, no evidence of a skull fracture, multiple small hemispheric
      contusions, severe cerebral edema secondary to ischemic encephalopathy, and
      axonal swellings in the corpus callosum, subcortical white matter, midbrain,
      right rostral inferior cerebellar peduncle, and medulla. This case of near sudden
      death confirms that blunt head trauma sustained during an assault can cause mild
      diffuse axonal injury. In addition, it is possible that sudden, alcohol
      intoxication-associated, craniofacial traumatic death is caused by acute
      dysfunction of the brainstem cardiorespiratory centers, whose capacity to correct
      potentially fatal dysrhythmias or apnea, induced by injury to their afferent
      axons, can be compromised by alcohol ingestion.

PMID- 7572862
TI  - Accidental fatal monochloroacetic acid poisoning.
AB  - A case of accidental lethal monochloroacetic acid poisoning is presented, along
      with a brief review of the mechanisms of intoxication. Although lethal skin
      exposures have been previously reported, this case appears to be the first
      instance of oral-route poisoning to be documented.

PMID- 7572863
TI  - Fatal hot coffee scald of the larynx. Case report.
AB  - We present a case of fatal upper aerodigestive tract scald sustained by a
      schizophrenic man who drank hot coffee. After describing the clinical and
      pathologic findings, we discuss the risks for incurring such injuries.

PMID- 7572864
TI  - Safety in bullet recovery procedures: a study of the Black Talon bullet.
AB  - Bullets or bullet fragments that are recovered during forensic autopsy and
      examined later as evidence may present hazards to both pathologists and forensic
      scientists due to sharp edges or jagged projections created by the deformation or
      fragmentation of a bullet upon impact with its target. The recent introduction of
      the Black Talon bullet has increased this hazard by its design, which produces a
      controlled expansion upon target impact that raises six harp edges from its
      copper jacket. We describe the appearance of the bullet along with methods for
      detection and recovery that can be applied as universal precautions of safe
      bullet handling.

PMID- 7572865
TI  - Longstanding intracardiac catheter embolism. An unusual autopsy finding.
AB  - The use of central venous catheters has greatly increased and so has the
      incidence of major complications. Catheter tip embolism is especially hazardous
      and sometimes may be fatal. We report a case of sudden death as a late and
      unusual complication of a catheter fragment embolism. The patient, a 39-year-old
      alcoholic man, suffered a nonreversible cardiac arrest shortly after his
      admission to hospital. Autopsy revealed a 54-cm-long fragment of an intravenous
      catheter in the right ventricle and the pulmonary trunk. Death was attributed to
      a cardiac arrhythmia.

PMID- 7572866
TI  - Bleeding as a source of lead particulates on clothing.
AB  - A review of several criminal cases where individuals were injured or killed by
      small-arms fire was conducted to ascertain the source of lead particulates
      discovered on the clothing of the shooting victims. In each of the reviewed
      cases, the garments were found to be free of gunpower particles. Additionally,
      the victims all sustained perforating gunshots from bullets possessing exposed
      lead on either the bearing surface or ogive. We theorized that the passage of the
      bullet through the body produces a trail of microscopic lead particles that are
      subsequently flushed out onto the clothing in the vicinity of the entrance and
      exit bullet holes. The discovery of these particles could lead to the mistaken
      opinion that their source is a close-proximity gunshot.

PMID- 7572868
TI  - Iatrogenic ruptures of the stomach after balloon tamponade. Two case reports:
      viscoelastic model.
AB  - Two cases of gastric rupture as a rare complication of balloon tamponade for
      esophageal varices are presented. In both cases, the rupture was caused by
      instillation of irrigation fluid without previous aspiration of stomach contents.
      In an experimental study, the stomachs of 11 corpses were filled with water to
      determine rupture pressure and volume. The mean rupture pressure was 73 +/- 13 mm
      Hg (9.7 +/- 1.7 kPa) and the mean rupture volume was 2,670 +/- 410 ml. A
      viscoelastic model was used for the representation of the relations between
      pressure and volume as well as pressure and time. Measured values are significant
      particularly for the explanation and medicolegal evaluation of iatrogenic
      ruptures of the stomach that occur during gastric lavage, positive pressure
      respiration, incorrect intubation, or forced mask respiration during
      resuscitation.

PMID- 7572869
TI  - Suffocation from use of modified gas mask.
AB  - We report a case of suffocation caused by use of a gas mask modified by the
      attachment of a plastic bag with evidence of halothane inhalation. Gas masks and
      plastic bags are sometimes used to aid in the inhalation of volatile substances.
      Improper use or modification of gas masks or other respiratory protection devices
      may result in asphyxial death.

PMID- 7572870
TI  - Superficial soft-tissue injury.
AB  - In 1992, Lee and Opeskin published an article on the little-recognized problem of
      death related to multiple superficial soft-tissue injuries following an assault.
      These deaths resulted from an acute assault and were restricted to young
      aboriginal women with a history of alcoholism. Presented here is a similar case
      occurring in a 22-year-old Polynesian woman. However, there are some significant
      differences. Aside from the final acute assault, there was evidence of chronic
      repeated episodes of superficial soft-tissue injury that resulted in undermining
      of connections between large areas of different tissue planes. These injuries
      produced pockets and spaces lined by fibrous tissue and numerous old
      intramuscular and subcutaneous hematomas, some of which showed secondary
      infection. There was also dense soft-tissue and subcutaneous fibrosis, and
      myositis ossificans.

PMID- 7572871
TI  - Endoscopic autopsy.
AB  - In cases in which the family of the deceased objects to the performance of a
      conventional autopsy for religious or other reasons, or where there are no
      forensic pathology facilities in the vicinity of the hospital, postmortem
      endoscopic examination may be an advantageous and cost-effective substitute for
      conventional necropsy, especially when the alternative is no postmortem
      examination at all. To test the reliability of postmortem endoscopy, conventional
      and endoscopic autopsies were performed on 20 cadavers at the L. Greenberg
      Institute of Forensic Medicine in Israel. Comparison of the findings of the two
      procedures showed a very high correlation (100%) for intraperitoneal and thoracic
      hemorrhages and hepatic, splenic, and diaphragmatic injuries; it showed a
      slightly lower correlation (60-80%) for mesenteric and retroperitoneal hematomas
      injuries to the great vessels, blood aspiration, and lung injury. Endoscopy
      failed to reveal the correct site of injury in the retroperitoneum and posterior
      aspect of the mediastinum. Collection of body fluids and tissue samples was
      possible by means of laparoscopy. The technique proved to be relatively accurate,
      more rapid than conventional autopsy, and left the body virtually intact.

PMID- 7572867
TI  - Spontaneous rupture of the spleen. A fatal complication of pregnancy.
AB  - Spontaneous splenic rupture in pregnancy is a rare and potentially catastrophic
      event. As many as 76 cases have been identified in the past 190 years by a
      variety of authors. This case report describes splenic rupture during the
      immediate postpartum period. The exact cause of the rupture could not be
      determined, and it was consistent with a spontaneous rupture.

PMID- 7572872
TI  - Two cases of lethal nitrazepam poisoning.
AB  - This case report describes two cases of lethal poisoning caused by a combination
      of advanced chronic disease and an overdose of nitrazepam. In both cases, a
      relatively small blood concentration of nitrazepam was found postmortem.

PMID- 7572874
TI  - Estimation of age from dentin by using the racemization reaction of aspartic
      acid.
AB  - To confirm the usefulness of the whole dentin in longitudinal sections for
      estimating age using the racemization ratio (D/L ratio) of aspartic acid, we
      compared longitudinal and transverse sections prepared from bilateral teeth in
      the same jaw of the same subjects. The D/L ratio was measured by gas
      chromatography. A better correlation between the D/L ratio and true age was
      observed when using longitudinal sections (r = 0.995) than when using transverse
      sections (r = 0.984-0.987). In the low age group, the D/L ratio was high in the
      crown and decreased toward the root apex. In the middle-advanced age groups,
      however, the D/L ratio was high in the crown as well as the area close to the
      root apex. The racemization reaction rate was higher in longitudinal than in
      transverse sections. These results suggest that the whole dentin in longitudinal
      sections of the central area of the tooth should be examined for accurate
      estimation of age.

PMID- 7572873
TI  - The time interval between lethal infant shaking and onset of symptoms. A review
      of the shaken baby syndrome literature.
AB  - Many health care professionals believe that there is a very short interval
      between an act of ultimately lethal infant shaking and the onset of symptoms
      (altered consciousness, convulsions, respiratory distress, and so on). We
      reviewed the English-language medical literature on the shaken baby syndrome for
      case reports or other information that documents the time of onset of symptoms
      after an act of ultimately lethal infant shaking. The medical literature contains
      minimal data that substantiate or contradict the contention that is stated here.

PMID- 7572875
TI  - A case of necrophilia in Medunsa.
AB  - Necrophilia is the erotic attraction to or a sexual interest in corpses. It is a
      rare sexual perversion that is seldom reported to police, published in the
      journals, or found in the forensic literature. It usually involves people who
      work with cadavers at mortuaries and funeral parlors. This case involved a
      teenage girl who had already been examined at autopsy.

PMID- 7572876
TI  - Suicidal shooting masked using a method described in Conan Doyle's novel.
AB  - The case of a suicide by gunshot is presented in which the person committing the
      suicide used a method described by Conan Doyle in one of his novels: conceal the
      weapon and make the suicide appear to be a homicide.

PMID- 7572878
TI  - Attempted suicide by intravenous injection of mercury: a rare cause of cardiac
      granulomas. A case report.
AB  - We present the autopsy findings of a case of attempted suicide by self
      administration of elemental mercury, resulting in mercury embolization to the
      heart and lungs. The person lived for 5 months afterward and subsequently died as
      a result of narcotic toxicity combined with loss of blood from an incised radial
      artery. A collection of metallic mercury droplets imbedded in a fibrous tissue
      granuloma was found in the apex of the right ventricular chamber, and metallic
      densities were seen on radiography of heart and lungs. The levels of mercury in
      various organs are shown, and the toxicology of elemental mercury is briefly
      discussed. The literature describing similar cases of metallic mercury emboli is
      reviewed. Owing to the apparent rarity of the phenomenon, many questions
      regarding the risk of death following intravenous injection of metallic mercury
      still remain unanswered.

PMID- 7572880
TI  - The need for death investigator training.

PMID- 7572877
TI  - Sudden death due to undiagnosed medullary-pontine astrocytoma.
AB  - A 20-year-old woman died suddenly and unexpectedly from low-grade medullary
      pontine fibrillary astrocytoma. She had experienced neurological symptoms
      including coughing and choking thought to be asthma, poor motor coordination,
      nasopharyngeal incompetence, and arm pain since the age of 11 months. Despite the
      long history of symptoms, the tumor remained clinically undiagnosed. This case
      demonstrates the minor, nonlocalizing, and relapsing remitting nature of symptoms
      and signs related to this slow-growing tumor. To the best of our knowledge, this
      is the first case of sudden, unexpected death due to brainstem glioma in the
      English-language literature. Since autopsy disclosed a 5-7 week pregnancy, this
      case is also an example of a rare cause of maternal death.

PMID- 7572881
TI  - Protective gloves for high-risk autopsies.

PMID- 7572879
TI  - Unexpected infant death in association with suspended rocking cradles.
AB  - We report on the deaths of two infants aged 10 1/2 and 11 weeks who were found
      face down in the angle between the base and side of their frame-suspended rocking
      cradles. Locking pins designed to prevent tilting of the cradles were not in
      place in either case. Investigation of the two cradles associated with the infant
      deaths and six other similar rocking cradles available for purchase in South
      Australia revealed either marked angles of tilt or inadequate or nonchildproof
      locking devices in all cases. A study of live control infants placed in similar
      situations demonstrated support for the possibility of positional asphyxia. We
      consider that these cases represent another potentially lethal sleeping
      environment for infants and emphasize the importance of death scene examination
      in all cases of unexpected infant death.

PMID- 7572882
TI  - Postmortem diffusion of alcohol from the stomach.
AB  - We explored postmortem ethanol diffusion from the stomach using a human cadaver
      model with multiple blood site sampling. In all, 400 ml of alcohol solution (5%,
      10%, 20%, or 40% methanol and ethanol weight/volume in water) was introduced into
      the stomach by oesophageal tube. Blood methanol concentrations correlated with
      ethanol concentrations (methanol range, 1-676 mg%; ethanol range, 1-531 mg%; r =
      0.9973). The pattern of ethanol diffusion showed marked between-case variability.
      Typically, concentrations were highest in pericardial fluid and, in decreasing
      order, in left pulmonary vein, aorta, left heart, pulmonary artery, superior vena
      cava, inferior vena cava, right heart, right pulmonary vein, and femoral vein.
      Diffusional flux was broadly proportional to the concentration of ethanol used.
      It was time-dependent (as assessed by 24-h and 48-h sampling) and markedly
      inhibited by refrigeration at 4 degrees C. After gastric instillation of 400 ml
      of 5% solution for 48 h at room temperature in paired cadavers, ethanol
      concentrations (mg%) were as follows: pericardial fluid 135, 222; aorta 50, 68;
      left heart 77, 26; right heart 41, 28; femoral vein 0. Using a 10% solution,
      ethanol concentrations (mg%) were as follows: pericardial fluid 401, 255; aorta
      129, 134; left heart 61, 93; right heart 31, 41; femoral vein 5, 7. Introducing
      50 ml of 10% alcohol solution into the oesophagus after oesophagogastric junction
      ligation produced similar aortic blood ethanol concentrations. This suggests that
      postmortem gastrooesophageal reflux and diffusion from the oesophagus is the
      mechanism of artefactual elevation of aortic blood ethanol.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7572883
TI  - Site dependence of postmortem blood methadone concentrations.
AB  - A case investigated by the Office of the Chief Medical Examiner, State of
      Maryland, identified methadone at a heart blood concentration of 2.4 mg/L and a
      subclavian blood concentration of 0.8 mg/L. Due to these discrepant results, a
      study was undertaken to determine whether such inconsistencies occurred in other
      methadone cases. Of the 15 cases studied, only four had heart blood and alternate
      blood concentrations within 20% of one another. In only 53% of the cases were
      variations of < 60% observed. The data failed to show a trend where one site was
      consistently higher or lower than the other site.

PMID- 7572884
TI  - Prediction rules for ulcerative colitis.

PMID- 7572885
TI  - A better biliary stent?

PMID- 7572888
TI  - Pneumatosis intestinalis: a review.
AB  - Pneumatosis intestinalis (PI) is an uncommon but important condition in which gas
      is found in a linear or cystic form in the submucosa or subserosa of the bowel
      wall. PI is a sign, not a disease; therefore, its relevance should be interpreted
      within the whole clinical context. PI has been found in several distinctive
      clinical settings: 1) in premature infants with necrotizing enterocolitis; 2) in
      adults with obstructive pulmonary disease; 3) in adults and children with a wide
      variety of associated conditions, including pyloric stenosis, jejunoileal bypass,
      progressive systemic sclerosis, transplantation, ischemic bowel, and drug
      therapy, particularly steroids, chemotherapy, and immunosuppression; 4) in adults
      as a primary benign problem; and 5) as an incidental finding in endoscopic
      mucosal biopsies. The two most important tasks of the physician include: 1)
      recognition of the entity of PI so that patients are not misdiagnosed and
      mismanaged as having malignancy or polyposis; and 2) differentiation of the
      benign variety, in which no intervention is indicated, from the life-threatening
      form, in which immediate surgery is necessary. Once life-threatening illnesses
      such as bowel necrosis, perforation, and infections are excluded, patients
      symptomatic from the cysts per se may be treated with oxygen and/or antibiotics.
      Because the reports of treatment of PI are at best anecdotal, the decision to
      treat and the treatment chosen should be carefully balanced with the risks.

PMID- 7572886
TI  - Gastric outlet obstruction malignant until proved otherwise.

PMID- 7572887
TI  - Swallowing and esophageal function in Parkinson's disease.
AB  - Dysphagia and drooling of saliva are frequent symptoms in Parkinson's disease
      (PD), occurring in one-half and three-quarters of all patients, respectively.
      Aspiration related to swallowing is a major cause of morbidity and mortality in
      PD. Defects in oral, pharyngeal, and esophageal phases of swallowing have been
      documented in patients with PD, and these defects precede symptoms. This paper
      reviews the current knowledge concerning swallowing abnormalities in PD. The
      pathogenesis of dysphagia and drooling of saliva is multifactorial, involving
      cognitive and psychological changes in addition to abnormalities of the
      extrapyramidal and autonomic nervous systems. Videofluoroscopic imaging of the
      upper esophageal sphincter and pharynx during mastication and swallowing has been
      the basis of our understanding of the mechanical malfunction present in patients
      with PD. Manometric abnormalities of the esophageal body and lower esophageal
      sphincter have also been documented. The use of combined manofluoroscopy to
      examine the upper esophageal sphincter and pharynx in PD offers great promise
      both in understanding the defects and directing therapy. Voluntary airway
      protection techniques may reduce aspiration, but they need to be tested in a
      clinical study. Such maneuvers may reduce the morbidity seen in PD.

PMID- 7572889
TI  - Evaluation of disease activity in patients with moderately active ulcerative
      colitis: comparisons between a new activity index and Truelove and Witts'
      classification.
AB  - OBJECTIVES: We have recently proposed a new activity index (AI) for ulcerative
      colitis. The aim of this study was to examine how AI would reflect the effect of
      medical therapy in comparison with Truelove and Witts' criteria. METHODS: In this
      trial, we studied 35 patients with extensive colitis who persisted with moderate
      disease for 2 wk. They showed no change in disease activity according to Truelove
      and Witts' classification despite 2 wk of corticosteroid therapy. Nine of the 35
      patients underwent surgery (operated group), and 26 responded to the medical
      therapy and went into remission (nonoperated group). RESULTS: In the nonoperated
      group, AI values significantly decreased at 1 and 2 wk after treatment compared
      with pretreatment values, whereas there was no significant change in AI in the
      operated group during the clinical course. Remission occurred in all patients
      indicating below 180 of AI values 2 wk after therapy, whereas approximately 65%
      of patients indicating above 180 of AI values subsequently needed colectomy.
      CONCLUSIONS: This study suggests that AI will be useful in evaluation of response
      to medical therapy and prediction of remission and colectomy in patients with
      moderately active ulcerative colitis.

PMID- 7572890
TI  - The Tannenbaum stent: a new plastic biliary stent without side holes.
AB  - OBJECTIVE: Clogging of plastic biliary stents used in malignant biliary
      obstruction remains a major problem. In vitro studies have shown that side holes,
      a standard feature of commercially available stents, may contribute to stent
      clogging. In a pilot study, we designed and prospectively evaluated a new biliary
      stent without side holes (Tannenbaum stent). METHODS: Over a 12-month period, 55
      consecutive patients (mean age 75 yr) with malignant distal common bile duct
      obstruction and without papillary or duodenal tumor infiltration underwent
      endoscopic placement of the Tannenbaum stent for the palliative treatment of
      jaundice. RESULTS: Tannenbaum stent insertion was technically successful on the
      first attempt in all patients and was accompanied by a significant reduction in
      mean serum bilirubin levels (10.1-1.6 mg%). Fifty-one patients were followed
      until death (median survival of 130 days); the symptomatic occlusion rate was
      16%, the dislocation rate was 8%, and the median stent patency was 64 wk. Aside
      from stent clogging, there were no complications. CONCLUSION: The Tannenbaum
      stent provided effective palliative biliary decompression in all patients. The
      patency rate was longer than that reported in the literature for conventional
      plastic stents with side holes and compared favorably with patency rates that
      have been reported for the metallic expandable biliary stents. The results of
      this pilot study are encouraging and warrant further studies.

PMID- 7572891
TI  - Malignancy is the most common cause of gastric outlet obstruction in the era of
      H2 blockers.
AB  - OBJECTIVES: To determine the relative incidence of malignant and nonmalignant
      pathology in patients presenting with gastric outlet obstruction in the era of H2
      blockers and to determine whether clinical features can differentiate between the
      two causes. METHODS: The charts of 33 consecutive patients with gastric outlet
      obstruction admitted to one institution between July 1990 and November 1993 were
      reviewed to determine etiology, management, and outcome. The diagnosis of gastric
      outlet obstruction was based on clinical presentation, an upper gastrointestinal
      barium study, and/or an inability during upper endoscopy to intubate the second
      portion of the duodenum. Patients with gastroparesis or a previously known cancer
      were excluded. RESULTS: Sixty-one percent (20 patients) had malignancy as the
      cause of their gastric outlet obstruction. Thirty-nine percent (13 patients) had
      benign disease. The patients with cancer tended to be older, and fewer had a
      history of peptic ulcer disease, although these factors were not statistically
      significant. The use of nonsteroidal anti-inflammatory drugs was not associated
      with gastric outlet obstruction. Four patients had malignancy that had not been
      suspected before operation despite numerous endoscopic and radiological studies.
      CONCLUSION: The incidence of malignancy in patients presenting with gastric
      outlet obstruction is greater than 50%. The etiology of gastric outlet
      obstruction cannot be predicted by age, history of peptic ulcer disease, or
      nonsteroidal anti-inflammatory drug use. The endoscopic treatment of gastric
      outlet obstruction should be approached with caution because malignancy cannot be
      reliably excluded by endoscopic or radiological studies.

PMID- 7572892
TI  - A pilot study of splenic and whole body retention of autologous radiolabeled
      leukocytes in the assessment of severity in inflammatory colitis.
AB  - OBJECTIVE: To assess the splenic and whole body retention of radiolabeled
      autologous leukocytes over 24 or 48 h as measures of the severity of colitis.
      METHODS: Eleven patients with colitis underwent standardized clinical,
      endoscopic, histological, and 111In-labeled leukocyte scintigraphy. A logistic
      discriminant analysis was used to estimate weighting factors for morphological
      indices, serum albumen, and stool excretion of 111In over 24 h that predicted the
      clinical assessment of severity. Subsequently, Spearman rank correlation analysis
      estimated associations among reductions in spleen and whole body radioactivity
      and the derived indices of inflammation. RESULTS: The reduction in spleen counts
      over 24 h correlates significantly with morphological indices (rs = 0.83, p <
      0.005) and with serum albumen and stool 111In (functional index, rs = 0.77, p <
      0.01). Similarly, the reduction in whole body 111In over 48 h correlates
      significantly with the combined index (rs = 0.8) and with the morphological and
      functional index separately (rs = 0.72 and 0.79, respectively). CONCLUSION: This
      pilot study identified weighting factors for morphological and functional indices
      in assessing severity of colitis; reduction in whole body and splenic retention
      of radioactivity was sufficient for evaluation of severity of colitis without the
      need for stool collections.

PMID- 7572893
TI  - High grade anal dysplasia in visually normal mucosa in homosexual men: seven
      cases.
AB  - BACKGROUND: Anal cancer and anal human Papillomavirus (HPV) infection are
      increased in homosexual men. METHODS: We screened high risk homosexual men as
      part of a longitudinal study examining the effect of HIV infection on the risk of
      development of high grade anal intraepithelial neoplasia (AIN II, III). RESULTS:
      We found seven men who had histological evidence of AIN II-III with visually
      normal findings by anoscopy. Two men were HIV-seronegative, five were HIV
      seropositive, and only one of the HIV-seropositive men had a low CD4 count < 200.
      Abnormal cytological results seen over follow-up periods of 3 months to 2.5 yr
      suggest the persistence of visually inapparent anal abnormalities. Two of the men
      had had small internal warts at earlier examinations, and three of the seven men
      subsequently developed visually abnormal anal findings. All men had HPV 16 DNA
      detected at some point. CONCLUSIONS: We hypothesize that high grade anal
      neoplasia may develop deep in the glands and can be detected by cytology before
      visible lesions are detected even with the aid of a colposcope. However, the
      implications of finding high grade anal cytology are not known at this time.
      Natural history studies are ongoing.

PMID- 7572894
TI  - Diverticular bleeding: are nonsteroidal anti-inflammatory drugs risk factors for
      hemorrhage and can colonoscopy predict outcome for patients?
AB  - OBJECTIVE: This retrospective study was performed to determine if certain
      endoscopic features of a bleeding diverticulum predict outcome for patients and
      to assess the role of nonsteroidal anti-inflammatory drugs (NSAID) as a risk
      factor for hemorrhage. METHODS: Over a 28-month period, colonoscopy was performed
      on 13 patients (mean, age 74 yr) in whom a specific diverticulum was
      unequivocally identified as a cause for bleeding. Endoscopic features of the
      affected diverticulum were recorded and correlated with outcome for patients.
      Drug histories were reviewed to document use of NSAID before bleeding. RESULTS:
      Three patients had a visible vessel located inside a diverticulum, and one
      subject had an adherent clot with active bleeding. These colonoscopic findings
      were classified as stigmata of significant hemorrhage (SSH). In the remaining
      nine patients the diverticula were ulcerated. This endoscopic finding was
      classified as stigmata of insignificant hemorrhage (SIH). Compared with patients
      with SIH, individuals with SSH experienced a greater number of bleeding episodes
      (3.5 vs 1.3, p = 0.006), had a lower initial hemoglobin concentration (8.2 vs
      12.5 gm%, p = 0.009), and required more transfusions (3.3 vs 0, p = 0.04) and
      invasive treatments (75% with SSH were managed by endoscopy or surgery vs 0% for
      those with SIH, p = 0.01). Ninety-two percent of the patients were taking NSAID
      (100% with SSH and 89% with SIH). Seventy-five percent of subjects with SSH
      compared with 0% of patients with SIH had a combined exposure to NSAID and ASA (p
      = 0.01). CONCLUSIONS: Presence of a visible vessel or an adherent clot with
      active bleeding is a reliable marker for significant hemorrhage. Ulcerated
      diverticula are the cause of trivial bleeding, and presence of this endoscopic
      finding accurately predicts a benign clinical course. NSAID may be an important
      risk factor for diverticular bleeding. It is possible that combined exposure to
      NSAID and ASA results in more severe bleeding compared with use of NSAID alone.

PMID- 7572896
TI  - Simultaneous prolonged recordings of proximal and distal intraesophageal pH in
      children with gastroesophageal reflux disease and respiratory symptoms.
AB  - OBJECTIVES: To characterize both proximal and distal esophageal acid exposure in
      children with gastroesophageal reflux-related respiratory disease and to
      investigate the usefulness of dual-channel intraesophageal pH monitoring in these
      patients. METHODS: Continuous simultaneous recording of distal and proximal
      esophageal pH was performed in 40 patients with gastroesophageal reflux disease
      and respiratory symptoms (wheezing, nocturnal cough, obstructive bronchitis) (age
      range 3-168 months) (group A), in 20 patients with reflux disease alone (age
      range 7-156 months) (group B), and in 14 controls (age range 5-108 months) (group
      C). RESULTS: (expressed as median +/- SD) 1) The two groups of patients did not
      differ with regard to distal and proximal esophageal acid exposure (percentage of
      reflux) during both the total recording period [distal, A: 9.2 +/- 4, B: 10.7 +/-
      7 (NS), C: 1.9 +/- 1.0; and proximal, A: 4.8 +/- 3.3, B: 4.0 +/- 3.3 (NS), C: 1.0
      +/- 0.7] and during nighttime [distal, A: 8.0 +/- 6.2, B: 10.4 +/- 6.1 (NS), C:
      0.9 +/- 0.65; and proximal, A: 3.72 +/- 3, B: 3.6 +/- 3.0 (NS), C: 0.75 +/-
      0.45]. 2) The two groups did not differ with regard to the ratio between proximal
      and distal esophageal acid exposure during both total and nocturnal periods of
      analysis. 3) No significant correlation was found between distal and proximal
      esophageal acid exposure during total and nocturnal recording periods. 4) In
      patients with reflux-related respiratory disease, the respiratory symptomatic
      index was significantly higher during distal esophageal acid exposure alone (47.0
      +/- 28.6%) than during simultaneous reflux at the two esophageal levels (26.9 +/-
      27%) (p < 0.05). Furthermore, reflux episodes associated with respiratory
      symptoms reached lower pH values than those in patients without symptoms at the
      two recording sites. CONCLUSIONS: Gastroesophageal reflux into the proximal
      esophagus does not discriminate between patients with reflux disease alone and
      those with reflux disease complicated by respiratory symptoms. Symptoms of asthma
      in reflux patients appear to be elicited more by a reflex mechanism than by
      aspiration of gastric refluxate into the airways. Intraesophageal acidification
      seems to be involved in eliciting respiratory symptoms related to reflux disease,
      and prolonged intraesophageal two-level pH measurement does not seem to be useful
      in the approach to patients with reflux disease associated with respiratory
      symptoms.

PMID- 7572895
TI  - Effect of cigarette smoking on gastroesophageal reflux measured by 24-h
      ambulatory esophageal pH monitoring.
AB  - OBJECTIVE: We reassessed the effect of cigarette smoking on gastroesophageal
      reflux because two previous ambulatory 24-h pH monitoring studies showed
      equivocal results and did not relate heartburn to changes in pH reflux events.
      METHODS: Our protocol design considered nicotine's pharmacokinetic half-life; 14
      smokers with heartburn and esophagitis abstained from smoking for 48 h before and
      during an ambulatory 24-h esophageal pH monitoring study (24-h pH). After
      resuming their smoking habits for 48 h or more, they underwent a second 24-h pH
      study and smoked 20 regular, filtered Marlboro cigarettes. Acid reflux was
      defined as a drop in intraesophageal pH to a value < 4 at 5 cm above the lower
      esophageal sphincter and was measured as percent exposure and reflux events
      (total N, those > or = 5 min, and longest event). Heartburn episodes were noted
      by the patients and were correlated later to acid reflux events. RESULTS:
      Cigarette smoking significantly increased the percentage time that the pH was < 4
      during a 24-h period from 7.35 to 11.1% (medians; p < 0.007). This increased
      exposure occurred predominantly during the day while in the upright posture and
      resulted from significant increases in both reflux events and those parameters
      that measure acid clearance (T events > or = 5 min and longest event). While
      smoking, the patients noted a 114% increase in daytime heartburn episodes that
      immediately followed a pH reflux event (3.5 to 7.5 episodes, medians; p < 0.009).
      CONCLUSIONS: Smoking 20 cigarettes has a greater effect on acid reflux and
      heartburn than purported.

PMID- 7572897
TI  - Psychological distress in patients with gastroesophageal reflux disease.
AB  - BACKGROUND: Psychological factors play a role in a variety of gastrointestinal
      illnesses, including esophageal diseases. The role of psychological factors in
      gastroesophageal reflux disease (GERD) is not known. The purpose of this study
      was to determine if psychological distress is present in patients with reflux
      disease. METHODS: We performed psychological assessments in 51 patients with
      documented gastroesophageal reflux disease and in 43 age-matched controls using a
      battery of instruments. RESULTS: Patients with reflux differed from controls on
      scales of depression, somatization, anxiety, and intensity of reporting symptom
      distress. However, a secondary analysis revealed that it was a subset of reflux
      patients (30%) that accounted for the differences between the two groups.
      CONCLUSIONS: These results suggest that although most patients with GERD are
      psychologically similar to patients without GERD, a subset of psychologically
      distressed patients are more likely to be found among patients with GERD. They
      suffer from general psychological distress rather than a specific psychiatric
      disorder. This psychological factor could affect the clinical manifestations of
      reflux disease in these individuals. Recognition and management of psychological
      distress in this subgroup may aid in the management of reflux disease.

PMID- 7572898
TI  - The effect of nasogastric intubation on gastroesophageal reflux: a comparison of
      different tube sizes.
AB  - OBJECTIVE: Previous reports have revealed conflicting conclusions about whether
      tubes placed across the esophagogastric junction (EGJ) have promoted reflux and
      whether there is potential for subsequent esophageal mucosal damage. The purpose
      of this study was to examine whether commonly used tubes (diameters: 2.1 mm,
      antimony pH probe and 3.8 mm, nasogastric tube) promote reflux under typical
      inpatient conditions. METHODS: Eight asymptomatic volunteers (five male, mean age
      27.6 yr) underwent three sessions, each lasting 6 hours postprandially, while
      supine with the head elevated 20 degrees. In randomized order, the subjects had
      either a 2.1-mm tube, 3.8-mm tube, and 2.1-mm tube together or no tube across the
      EGJ. The subjects were fed 500 ml of Ensure Plus at the beginning of the study.
      Reflux was measured by a pH probe placed 5 cm above the lower esophageal
      sphincter. The number of reflux episodes, number of reflux episodes more than 5
      minutes, longest reflux episode, time esophageal pH was less than 4, and
      percentage total time pH was less than 4 were evaluated. RESULTS: Over the 6
      hours, no abnormal reflux was shown with either tube size across the EGJ.
      CONCLUSIONS: Over a 6-h period, a tube (pH probe alone or combined with
      nasogastric tube) across the EGJ does not promote an increase in the amount of
      postprandial supine gastroesophageal reflux in normal volunteers.

PMID- 7572899
TI  - E-cadherin expression in gastroesophageal reflux disease, Barrett's esophagus,
      and esophageal adenocarcinoma: an immunohistochemical and immunoblot study.
AB  - BACKGROUND/AIMS: Cadherins are cell adhesion molecules that are thought to play a
      vital role in cell-cell adhesion; loss or down-regulation of their expression has
      been implicated in neoplasia. Barrett's esophageal columnar metaplasia (BE) is a
      premalignant lesion for esophageal adenocarcinoma with clinical symptoms similar
      to those of gastroesophageal reflux disease and esophagitis. In this study, we
      investigated the potential relationship between E-cadherin expression and
      inflammation, metaplasia, and carcinogenesis in esophagitis, BE, and esophageal
      adenocarcinoma. METHODS: Endoscopically obtained mucosal biopsy specimens of
      esophagitis (n = 6), BE with or without dysplasia (n = 16), and esophageal
      adenocarcinoma (n = 6) were analyzed for the expression of E-cadherin by both
      Western analysis and immunoperoxidase staining. RESULTS: Densitometric analysis
      of Western blots revealed the expression of E-cadherin to be significantly lower
      in patients with BE compared with normal esophageal epithelium, regardless of the
      presence or absence of dysplasia (p < 0.03). No significant differences were
      noticed between the normal esophagus and the esophagitis groups. In the
      adenocarcinoma group, one patient showed complete loss of E-cadherin expression,
      and the other five patients showed significantly reduced expression that was even
      lower than that in BE (p < 0.01). Immunoperoxidase staining matched the Western
      analysis results. CONCLUSIONS: We conclude that loss of or reduced E-cadherin
      expression may play a role in the progression of BE to adenocarcinoma.

PMID- 7572900
TI  - A systematic review of the association between Barrett's esophagus and colon
      neoplasms.
AB  - OBJECTIVE: Patients with Barrett's esophagus may be at increased risk of colon
      neoplasms, including cancer. However, different studies of this have yielded
      conflicting results. The objective of this analysis was to review all existing
      published data in an attempt to determine whether there is such an association
      and, if so, to estimate the level of risk. METHODS: We have reviewed all of the
      published studies examining the prevalence of colon neoplasms in patients with
      Barrett's esophagus. We have compared these with a cohort of patients drawn from
      the general population and participating in colorectal cancer screening programs.
      RESULTS: The prevalence of colon cancer in patients with Barrett's esophagus was
      7.6% compared with 1.6% in the control group. The pooled odds ratio for colon
      cancer in Barrett's esophagus was 5.19 (p < 0.0001). In a small subgroup
      analysis, the odds ratio for colon cancer in patients identified as having
      Barrett's esophagus with specialized columnar epithelium was 8.71 (p < 0.0001).
      CONCLUSIONS: We conclude that patients with Barrett's esophagus have an increased
      risk of colon cancer. This may be particularly true in those patients with
      specialized columnar epithelium.

PMID- 7572901
TI  - Salivary-specific immunoglobulin G in the diagnosis of Helicobacter pylori
      infection in dyspeptic patients.
AB  - OBJECTIVES: Helicobacter pylori infection is arguably the most common chronic
      bacterial infection in humans. The high prevalence and the association with
      peptic ulceration and gastric cancer indicate that simple, noninvasive methods
      for diagnosis of the infection are needed. In this study, the accuracy of
      salivary diagnosis for H. pylori infection was assessed. METHODS: Saliva and
      serum samples of 152 dyspeptic patients were tested for H. pylori IgG and IgA by
      an in-house ELISA. All patients underwent gastroscopy with biopsy. RESULTS: One
      hundred thirty-one patients (86%) were found to be H. pylori positive on
      histology. Duodenal ulcer was found in 67 patients; 85 had no macroscopic lesion.
      Salivary and serum H. pylori IgG as well as serum H. pylori IgA titers were
      significantly higher in H. pylori-positive than in H. pylori-negative patients.
      The sensitivity and specificity of salivary H. pylori IgG were 82% and 71%,
      respectively; the positive and negative predictive values were 95% and 40%,
      respectively; and the accuracy 81%. The corresponding figures for serum H. pylori
      IgG were 97% and 91%; 98% and 83%; and 96%. Those for serum H. pylori IgA were
      80% and 52%; 91% and 30%; and 76%. The sensitivity of salivary H. pylori IgG in
      detecting duodenal ulcer was 83% (56/67) that of serum H. pylori IgG was 97%
      (65/67) (odds ratio = 0.15; confidence interval = 0.02-0.8; p = 0.02).
      CONCLUSIONS: Salivary H. pylori IgG was a fairly sensitive and accurate indicator
      of gastric H. pylori colonization, with a high positive predictive value in our
      population. Data, however, suggest that salivary H. pylori IgG measurements do
      not compare favorably with serology.

PMID- 7572902
TI  - The effects of short-term lansoprazole therapy on Helicobacter pylori infection
      and antral gastritis in duodenal ulcer patients.
AB  - BACKGROUND/AIMS: Lansoprazole is a new potent proton pump inhibitor that exhibits
      activity against Helicobacter pylori in vitro. This study endeavored to determine
      the effects of 4 wk of lansoprazole therapy upon H. pylori infection and antral
      gastritis in duodenal ulcer patients and to determine the relationship of the
      gastritis with Helicobacter infection and with ulcer activity. METHODS:
      Satisfactory antral biopsies were obtained from 119 duodenal ulcer patients
      before and after 4 wk of therapy with lansoprazole, ranitidine, or placebo.
      Sections were scored blindly for degree of active and chronic inflammation and
      extent of H. pylori infection. RESULTS: Four weeks of lansoprazole (30 mg daily)
      or ranitidine (300 mg daily) therapy produced a significant decrease in H. pylori
      infection. The reduction of H. pylori infection, but not ulcer healing per se,
      correlated with the decrease in active and chronic antral inflammation. Reduction
      of H. pylori infection, however, did not improve the good ulcer-healing rates
      already achieved at 4 wk by potent acid inhibition. CONCLUSIONS: Lansoprazole
      exhibits activity against H. pylori in vivo. Short-term improvement in antral
      gastritis is affected by reduction of H. pylori infection but not by ulcer
      healing.

PMID- 7572904
TI  - Fecal elastase test: evaluation of a new noninvasive pancreatic function test.
AB  - OBJECTIVES: Pancreatic elastase is highly stable along the intestinal tract. A
      new ELISA is commercially available to measure human specific elastase-1
      concentration in stool. We evaluated the behavior of this fecal elastase test
      (FET) compared with other indirect pancreatic function tests in patients with
      chronic pancreatitis (CP). METHODS: A total of 69 patients were included in the
      study, 20 of whom were diagnosed with CP according to the findings on ERP and CT;
      13 patients had other pancreatic diseases, and the remaining 36 patients had
      gastrointestinal or hepatic disorders. All patients' elastase-1 concentrations
      and chymotrypsin activities [fecal chymotrypsin test (FCT)] were measured, and
      the serum pancreolauryl test (PLT) was performed. RESULTS: Similar to PLT, fecal
      elastase concentration was significantly decreased in patients with moderate and
      severe CP (assessed by ERP) compared with patients with extrapancreatic
      disorders. However, and contrarily to PLT, FET was not affected by gastric
      resection, malabsorption due to intestinal disease, or marked alteration of the
      gastric motility. The sensitivity of FET was 100% for moderate to severe CP but
      0% for mild CP; the specificity was 83%. Compared with other indirect pancreatic
      function tests, FET appears to be as sensitive as PLT and as specific as FCT, and
      it is clearly more specific than PLT and more sensitive than FCT. Unlike FCT, FET
      was not affected by oral enzyme supplementation. CONCLUSION: FET is a simple and
      accurate functional test for CP, and it is hardly influenced by extrapancreatic
      disorders or therapy with exogenous enzymes.

PMID- 7572903
TI  - Electron microscopic study of association between coccoid forms of Helicobacter
      pylori and gastric epithelial cells.
AB  - OBJECTIVE: To investigate the relationship between helical and coccoid forms of
      Helicobacter pylori and gastric epithelial cells. METHODS: Gastric antral and
      body biopsies were obtained from eight children, aged 10-17 yr, who underwent
      diagnostic gastroscopy. Specimens were processed for electron microscopy. The
      location of organisms and ultrastructural features were assessed with a
      transmission electron microscope. RESULTS: We observed two morphological forms of
      bacteria in three of eight H. pylori-positive patients. Helical forms were
      localized only in the proximity to unchanged or variously damaged mucous cells,
      but coccoid forms were present only above strongly damaged epithelial cells.
      CONCLUSION: Coccoid forms of H. pylori are closely associated with damaged
      gastric mucous cells. Possible explanations for this phenomenon are discussed.

PMID- 7572905
TI  - Screening for celiac disease in first-degree relatives of patients with celiac
      disease by lactulose/mannitol test.
AB  - OBJECTIVES: In first-degree relatives of celiac patients, the risk of
      oligosymptomatic celiac disease is elevated. These individuals therefore also
      have a higher potential for malignancy or nutritional deficiencies.
      Lactulose/mannitol permeability is increased in untreated celiac patients and has
      been recommended to screen for celiac disease. We investigated the usefulness of
      a lactulose/mannitol home test kit for screening first-degree relatives home test
      kit for screening first-degree relatives of celiac patients. METHODS: The
      lactulose/mannitol test was performed at home by 111 first-degree relatives.
      These subjects received the test kit from celiac index patients, were instructed
      by an information sheet how to carry out the test, and were asked about their
      symptoms by questionnaire. When lactulose/mannitol permeability was abnormal,
      endomysial antibodies were tested by immunofluorescence. Any relatives with
      positive endomysial antibodies were then biopsied. To investigate the specificity
      of the lactulose/mannitol test for celiac disease, 40 patients with nonspecific
      gastrointestinal symptoms were tested. RESULTS: Lactulose/mannitol permeability
      was elevated in 34 (31%) relatives, but only nine (8%) of those relatives showed
      positive endomysial antibodies. Flat mucosa was found in all nine relatives after
      biopsy. The prevalence of celiac disease was much higher (42%) among 12 relatives
      who contacted the outpatient clinic themselves because of symptoms. Seventy-one
      percent of the remaining 21 relatives with elevated permeability demonstrated
      normal intestinal permeability at a control test within 1 yr. CONCLUSION: By
      combining the lactulose/mannitol test with endomysial antibody testing, we have
      developed a good strategy for use in screening for celiac disease among first
      degree relatives.

PMID- 7572906
TI  - Clinicopathological assessment of hepatitis C virus infection in parenteral drug
      abusers.
AB  - OBJECTIVES: To determine the severity of hepatic histological lesions in anti-HCV
      positive parenteral drug abusers and to correlate it with the level of ALT
      activity and HCV RNA determined by polymerase chain reaction (PCR). METHODS:
      Twenty-nine of the 62 anti-HCV-positive parenteral drug abusers who consecutively
      entered a Rehabilitation Center of Athens consented to liver biopsy and were
      prospectively and thoroughly followed up for a mean of 12.9 (range 6-33) months.
      Anti-HCV was detected by a second-generation enzyme immunoassay and confirmed by
      a second-generation recombinant immunoblot assay. Serum samples were tested for
      HCV RNA by nested PCR with primers from the highly conserved 5' untranslated
      region of the HCV genome. RESULTS: Liver biopsy revealed lesions compatible with
      chronic hepatitis in 26 (89.6%) and a normal liver in three (10.4%) of the 29
      patients. In particular, 11 (37.9%) had minimal and 15 (57.1%) had mild chronic
      hepatitis; fibrosis was absent or mild in all cases. Histological grade and stage
      were significantly milder in patients with persistently normal ALT activity than
      in those with increased ALT activity. However, chronic hepatitis was observed in
      five (62.5%) of the eight patients with normal ALT levels. The presence of serum
      HCV RNA was not significantly correlated with the severity of histological
      lesions. HCV RNA was detected in 16 (57.1%) of the 28 cases tested. In
      particular, HCV RNA was detected in one (33.3%) of the three cases with normal
      liver and in three (37.5%) of the eight patients with normal ALT levels.
      CONCLUSIONS: Liver biopsy appears to be the method of choice for the accurate
      evaluation of anti-HCV positive parenteral drug abusers, irrespective of ALT
      activity and presence of serum HCV RNA. Chronic hepatitis is observed in the
      majority and the state of "healthy" carrier of HCV in the minority of this
      epidemiological setting.

PMID- 7572907
TI  - Serum cryoglobulin and chronic hepatitis C virus disease among Japanese patients.
AB  - OBJECTIVES: Hepatitis C virus (HCV)-associated mixed cryoglobulins appear to be
      detected often in hepatitis C-related chronic liver disease. The association of
      the two phenomenon among Japanese patients is the subject of the present study.
      METHODS: Serum levels of total hemolytic complement (CH50) and anti-C3d-binding
      immune complex, as well as the prevalence of cryoglobulins, were studied in 213
      patients with chronic liver disease (hepatitis C, 155; hepatitis B, 58).
      Cryoprecipitates were tested for anti-HCV Ab and HCV RNA. RESULTS: CH50 activity
      was significantly lower in patients with hepatitis C than in those with hepatitis
      B except in responders to interferon who showed a sustained loss of HCV RNA.
      Cryoglobulins were detected in 24 (37%) of 65 patients with hepatitis C; they
      generally consisted of polyclonal immunoglobulins but one case. Cryoglobulins
      were more frequently observed in cirrhotic patients and in those with a longer
      duration of disease. Cryoglobulinemia-related clinical signs such as vasculitis
      occurred in only three cases. Patients with cryoglobulins had lower CH50 activity
      and higher immune complex values than those without cryoglobulins. Anti-HCV Ab
      and HCV RNA were detected in all cryoprecipitates tested. CONCLUSIONS: These
      findings suggest that HCV is a major cause of cryoglobulins and advanced liver
      damage. However, serum cryoglobulins with polyclonal immunoglobulins appear to be
      less frequent among Japanese patients than among those studied in Western
      countries.

PMID- 7572908
TI  - Prognostic significance of hepatic vein waveform by Doppler ultrasonography in
      cirrhotic patients with portal hypertension.
AB  - OBJECTIVE: We prospectively evaluated the prognostic value of the flat hepatic
      vein waveform, measured by Doppler ultrasound, in cirrhotic patients with portal
      hypertension. METHODS: The Doppler pattern of right and left hepatic veins in a
      series of 120 consecutive cirrhotic patients with portal hypertension but without
      hepatocellular carcinoma was examined, together with clinical and biochemical
      parameters. RESULTS: Flat waveform of the right hepatic vein was recognized in
      nine patients and that of the left hepatic vein was seen in 13. After a mean
      follow-up of 13.6 +/- 9.7 months, 17 patients died, all from liver failure. In
      the univariate analysis, variable significantly associated with the duration of
      survival were age, etiology of the liver cirrhosis, upper gastrointestinal
      bleeding after start of the study, Child-Pugh score, ascites, encephalopathy,
      prothrombin index, bilirubin, albumin, and flat Doppler waveform in the right and
      left hepatic veins. Multivariate analysis showed that flat Doppler waveform in
      the right hepatic vein, bilirubin, and prothrombin index were independently
      related to survival. CONCLUSIONS: The prognostic accuracy in cases of cirrhosis
      with portal hypertension is significantly improved with acquisition of
      information obtained from hepatic vein waveform by Doppler ultrasound.

PMID- 7572909
TI  - Extensive spreading carcinoma of the esophagus with invasion restricted to the
      submucosa.
AB  - OBJECTIVES: The aim of this study was to examine the clinicopathological features
      of extensive spreading type of squamous cell carcinoma (SCC) of the esophagus
      with invasion restricted to the submucosa. METHODS: Thirty-eight submucosal SCC
      were studied histopathologically, and five of these 38 submucosal SCC, which
      demonstrated an extensive spreading-type SCC in which the size of the SCC was
      over 5 cm in longitudinal length while extending entirely across the esophageal
      lumen in a circumferential spread, are described in detail. RESULTS: The extent
      of SCC depended mainly on the extent of intraepithelial carcinoma (IEC) and
      ranged from 50 to 135 mm in longitudinal length. IEC existed continuously in four
      cases, and multiple IEC existed separately in one case. An epithelium showing
      dysplasia was present in all cases, and the involvement of the glands and ducts
      by IEC was present in two cases. There was only one invasive part of SCC observed
      in one case, and three to 10 invasive parts of SCC were observed in the other
      four cases; various features of invasion, including an invasive SCC from the
      esophageal glands and ducts, were also present. CONCLUSIONS: The extensive
      spreading-type SCC of the esophagus, which was considered to result from the
      widespread or multiple carcinomatous changes of the esophageal epithelium, was
      found to not be as rare as generally thought. The multiple and various features
      of the invasive parts of SCC suggested the simultaneous development of a downward
      invasion of SCC at different areas in extensive IEC.

PMID- 7572910
TI  - Parathyroid hormone-related protein expression in human gastric adenocarcinomas
      not associated with hypercalcemia.
AB  - OBJECTIVE: Our evaluation of a patient with a parathyroid hormone-related protein
      (PTHrP)-producing gastric adenocarcinoma and hypercalcemia prompted us to study
      the expression of PTHrP in 13 additional patients with gastric cancer and in 10
      control cases. Our objective was to investigate by immunohistology the expression
      of PTHrP in gastric cancer. METHODS: Immunohistology studies were conducted with
      two murine monoclonal antibodies to synthetic peptides of human PTHrP, 9H7, and
      8B12. The 9H7 antibody was raised to the carboxy-terminal amino acid fragment
      (109-141) of PTHrP, and the 8B12 antibody was raised to the amino-terminal amino
      acid fragment (1-34) of PTHrP. RESULTS: Paraffin-embedded tumor specimens from 13
      of 14 cases of gastric adenocarcinoma stained positively with the antibody to the
      carboxy terminus of the PTHrP peptide, but none stained positively with the
      antibody directed against the amino terminus. None of 10 control cases stained
      positively with either antibody. The staining was predominately evident in the
      cytoplasm of the tumor cells. Except for the sentinel case, none of the other
      patients with gastric adenocarcinoma had hypercalcemia. Thus, gastric
      adenocarcinoma seems to rarely result in systemic hypercalcemia. CONCLUSIONS: Our
      studies demonstrated that abnormal PTHrP production can occur in malignant cells
      without producing hypercalcemia. PTHrP may play a role in the pathogenesis of
      gastric adenocarcinoma that is independent of its hypercalcemic effects. PTHrP
      measurements may be clinically valuable in patients with cancer who are not
      hypercalcemic.

PMID- 7572911
TI  - Eosinophilic gastroenteritis involving the entire digestive tract.
AB  - Eosinophilic gastroenteritis, an inflammatory disease of unknown etiology,
      commonly involves the stomach and small intestine with eosinophilic infiltration.
      Herein we describe an unusual case of eosinophilic gastroenteritis involving the
      entire digestive tract. A 24-yr-old woman came to our hospital presenting with
      diarrhea with marked peripheral eosinophilia. Stool specimens were negative for
      parasites, ova, bacteria, and fungi. Barium and endoscopic studies showed
      thickened edematous folds of the duodenum and small intestine. Biopsy specimens
      of the esophagus, stomach, duodenum, ileum, and colon showed eosinophilic
      infiltration. A diagnosis of eosinophilic gastroenteritis involving the entire
      digestive tract was made, and therapy with prednisone was started. Symptoms and
      peripheral eosinophilia rapidly resolved, and biopsies of the digestive tract
      demonstrated no eosinophilic infiltration. This case illustrates the expanded
      spectrum of the disease to the entire digestive tract and emphasizes the
      diagnostic usefulness of endoscopic biopsies. The initial presentation of
      patients with eosinophilia requires the evaluation of the entire digestive tract.
      It is worth noting that eosinophilic gastroenteritis can involve the entire
      digestive tract.

PMID- 7572912
TI  - A case of diclofenac-induced colitis with focal granulomatous change.
AB  - We report a case of severe colitis from diclofenac (Voltaren), one of a number of
      nonsteroidal anti-inflammatory drugs (NSAIDs) that can cause colonic injury. The
      patient, a 68-yr-old woman, presented with acute onset of bloody diarrhea, having
      taken diclofenac for more than 2 yr. Colonoscopy revealed deep ulcerations in the
      transverse colon and erythema and erosions scattered elsewhere. Biopsy findings
      included crypt distortion, cryptitis, hemorrhage, and some fibrosis. Also, in one
      biopsy taken from an area of deepest ulceration, a large, non-foreign body-type
      granuloma was seen, raising the specter of Crohn's colitis. All symptoms subsided
      within 24 h after discontinuation of the diclofenac, and follow-up colonoscopy 17
      days later showed complete endoscopic and histological resolution. Patients and
      physicians should be aware of the possibility of colitis from NSAIDs. In rare
      cases, some will show granulomatous change that may be confused with Crohn's
      disease. Early recognition and discontinuation of NSAIDs is crucial to prevent
      clinical worsening that could lead to colectomy or even prove fatal.

PMID- 7572913
TI  - Control of gastric acid with high dose H2-receptor antagonists after omeprazole
      failure: report of two cases.
AB  - Successful omeprazole therapy in patients with symptomatic gastroesophageal
      reflux (GER) refractory to treatment with H2-receptor antagonists has often been
      reported. In contrast, successful treatment of GER by H2-receptor antagonists in
      patients resistant to the acid-suppressing effects of omeprazole is rarely
      reported. We describe two patients who demonstrated therapeutic responses to high
      dose H2-receptor antagonists after high dose omeprazole failed to suppress
      gastric acidity and GER.

PMID- 7572914
TI  - Hemosuccus pancreaticus as a source of obscure upper gastrointestinal bleeding:
      three cases and literature review.
AB  - We report three patients with chronic pancreatitis and recurrent episodes of
      severe upper gastrointestinal bleeding caused by hemosuccus pancreaticus. No
      bleeding source could be identified despite repeated endoscopies. In two
      patients, angiography disclosed a fistula between a peripancreatic artery and a
      pancreatic pseudocyst. In one patient, a fistula between the splenic artery and
      the pancreatic duct was found intraoperatively. No rebleeding occurred after
      operation. In cases of obscure upper gastrointestinal hemorrhage, the pancreas
      should be considered as a bleeding source, especially in patients with chronic
      pancreatitis.

PMID- 7572916
TI  - Unusual presentation of an unusual type of choledochal cyst.
AB  - Type II choledochal cysts are rare congenital malformations of the biliary ductal
      system. We report a case in which a type II choledochal cyst presented as a mass
      in the porta hepatis without any demonstrable connection with the biliary tree.
      In the English literature, this is the first described case of this type in the
      absence of biliary tract malignancy. We hypothesize that the connection to the
      biliary tree was lost by either torsion of the cyst or fibrosis due to chronic
      inflammation.

PMID- 7572915
TI  - Appendiceal endometriosis presenting as massive lower intestinal hemorrhage.
AB  - Appendiceal endometriosis is a very uncommon clinical entity. We describe a 33-yr
      old white female who presented with painless profuse rectal bleeding. Emergency
      colonoscopy revealed bleeding from the appendiceal opening. An emergency
      appendectomy was performed which controlled her bleeding. The histopathological
      examination demonstrated appendiceal endometriosis. Painless bleeding from
      appendiceal endometriosis is extremely rare; however, it should be considered
      when evaluating young women of reproductive age who present with rectal bleeding.

PMID- 7572917
TI  - Pneumocystis carinii pneumonia complicating methotrexate treatment of primary
      sclerosing cholangitis.
AB  - The etiology of primary sclerosing cholangitis, a chronic progressive cholestatic
      liver disease, is poorly understood. Treatment with oral methotrexate may improve
      patient symptoms, liver biochemistry, and hepatic histology. This report
      describes a severe life-threatening complication of methotrexate therapy in
      primary sclerosing cholangitis--the development of Pneumocystis carinii
      pneumonia. The reported cases of methotrexate-associated P. carinii pneumonia in
      the literature are reviewed. With the increasing use of methotrexate in chronic
      inflammatory disorders, physicians should be aware of this potentially lethal
      complication.

PMID- 7572918
TI  - Traumatic neuroma of the common hepatic duct after laparoscopic cholecystectomy.
AB  - Jaundice and stricture of the common hepatic duct were detected in a 53-yr-old
      woman 2 months after she had laparoscopic cholecystectomy for a gallstone. Then
      she underwent resection of the stricture part of the duct and hepaticojejunostomy
      which was effective. Pathological examination showed that traumatic neuroma,
      probably caused by bile leakage after cauterization, led to stricture of the
      common bile duct.

PMID- 7572919
TI  - Multiple ulcerative esophagitis caused by alendronate.

PMID- 7572920
TI  - Chronic idiopathic ulcer of the ileum in the acquired immune deficiency syndrome.

PMID- 7572921
TI  - Clostridial splenic abscess: diagnosis, treatment, and outcome.

PMID- 7572922
TI  - Intussusception of the appendix due to endometriosis.

PMID- 7572923
TI  - Is short segment Barrett's clinically significant?

PMID- 7572924
TI  - The association of reovirus 3 and biliary atresia: finally resolved?

PMID- 7572925
TI  - Pancreas divisum.

PMID- 7572927
TI  - How many are too many?

PMID- 7572926
TI  - Pleural effusions: a new negative prognostic parameter for acute pancreatitis.
      Response to Dr. Lankisch et al.

PMID- 7572929
TI  - Do Helicobacter pylori-positive duodenal ulcers have an increased risk of
      bleeding?

PMID- 7572928
TI  - Low prevalence of Helicobacter pylori in inflammatory bowel disease: association
      with sulfasalazine.

PMID- 7572930
TI  - Colectomy in a constipated scleroderma patient: a word of caution.

PMID- 7572931
TI  - A very rare case of continuous ambulatory peritoneal dialysis peritonitis caused
      by Anisakis larva.

PMID- 7572932
TI  - Esophageal carcinoma with a sinus tract: closure of the tract with primary
      chemotherapy and radiation therapy.

PMID- 7572934
TI  - A case of Chilaiditi's syndrome associated with strangulated volvulus of the
      sigmoid colon.

PMID- 7572933
TI  - Psychological stress and disease activity in ulcerative colitis: a
      multidimensional cross-sectional study.

PMID- 7572935
TI  - Trypsin-like effect on Vero cells in fecal specimens from diarrheal patients.

PMID- 7572936
TI  - Endoscopic appearance of a gallbladder-sealed perforated duodenal ulcer.

PMID- 7572937
TI  - Health effects of westernization and migration among Chamorros. 1970.

PMID- 7572938
TI  - Transferrin saturation and risk of cancer.
AB  - The authors examined the hypothesis that relatively high levels of transferrin
      saturation increase the risk of cancer. They studied a cohort of prepaid health
      plan members whose transferrin saturation levels were measured during the period
      1969-1971 and who were followed for cancer through 1990. After the exclusion of
      10 percent of the subjects who received treatment for one or more of six chronic
      conditions or who were pregnant when the measurement was made and persons who
      contributed less than 5 years of follow-up, the authors were left with 38,538
      persons who were followed for an average period of 17.7 years. In women, a
      positive association was observed between transferrin saturation and risk of
      stomach carcinoma (> or = 34.5% compared with < or = 20.3%: relative risk (RR) =
      3.5, 95% confidence interval (CI) 0.98-12). In men, transferrin saturation was
      inversely associated with risk of colon and rectal carcinoma (> or = 40.7%
      compared with < or = 26.0%: colon, RR = 0.62, 95% CI 0.35-1.1; rectum, RR = 0.30,
      95% CI 0.08-1.1) and with non-Hodgkin's lymphoma (32.1-40.6% compared with < or =
      26.0%: RR = 0.31, 95% CI 0.11-0.88; no cases observed with transferrin saturation
      > or = 40.7%). The authors did not find evidence that the risk of epithelial
      cancer (all sites combined) was related to transferrin saturation level or to
      iron deficiency (< or = 15%) or overload (> or = 60%).

PMID- 7572939
TI  - Gamma-glutamyltransferase: determinants and association with mortality from
      ischemic heart disease and all causes.
AB  - The association of serum levels of gamma-glutamyltransferase (GGT) with
      cardiovascular disease risk factors, and with mortality from all causes,
      cardiovascular disease, and non-cardiovascular diseases, has been examined in a
      prospective study of 7,613 middle-aged British men followed for 11.5 years. GGT
      levels were strongly associated with all-cause mortality, largely due to a
      significant increase in deaths from ischemic heart disease and other non
      cardiovascular disease causes, i.e., non-cancer deaths, in the top quintile of
      the GGT distribution. No association was seen with cancer mortality. However, GGT
      was significantly (positively) associated with alcohol intake, body mass index,
      smoking, preexisting ischemic heart disease, diabetes mellitus, antihypertensive
      medication, systolic and diastolic blood pressure, total and high density
      lipoprotein cholesterol, heart rate, and blood glucose, and negatively associated
      with physical activity and lung function (forced expiratory volume in 1 second
      (FEV1)). After adjustment for these personal characteristics and biologic
      variables, elevated GGT (highest quintile > or = 24 unit/liter vs. the rest) was
      still associated with a significant increase in mortality from all causes
      (relative risk (RR) = 1.22, 95% confidence interval (CI) 1.01-1.42; n = 818
      deaths) and from ischemic heart disease (RR = 1.42, 95% CI 1.12-1.80; n = 332
      deaths). The increase in other non-cardiovascular disease causes was of marginal
      significance (RR = 1.45, 95% CI 0.95-2.20; n = 127 deaths). When examined
      separately by the presence or absence of preexisting ischemic heart disease, the
      increased risk of ischemic heart disease mortality was more marked in those with
      evidence of ischemic heart disease at screening, particularly in those with
      previous myocardial infarction (RR = 1.67, 95% CI 1.03-2.69; n = 84 deaths). The
      increased risk of other non-cardiovascular disease deaths was only seen in men
      without preexisting ischemic heart disease, largely due to an excess of hepatic
      cirrhosis. In summary, many factors other than alcohol intake are associated with
      increased levels of GGT, in particular body mass index, diabetes mellitus, and
      serum total cholesterol. The finding of increased risk of ischemic heart disease
      mortality seen in men with preexisting ischemic heart disease is related to the
      severity of the underlying myocardial damage. The biologic significance of raised
      GGT in men with preexisting ischemic heart disease merits further study.

PMID- 7572941
TI  - Comparison of methods of estimating the mother-to-child transmission rate of
      human immunodeficiency virus type 1 (HIV-1). New York City Perinatal HIV
      Transmission Collaborative Study Group.
AB  - Four methods of estimating mother-to-child transmission rates of human
      immunodeficiency virus type 1 (HIV-1), based on the 1992 Ghent workshop, were
      compared in a multicenter New York City prospective cohort study in 1986-1992. Of
      833 infants born to women at risk of HIV-1 infection, 388 were born HIV-1
      seropositive and 445 were HIV-1 seronegative. The four methods, the Antibody
      Only, Indirect, Direct, and Virologic Methods, yielded transmission rate
      estimates of 19-25%, classifying 59-89% of the cohort. Estimation based on
      persistence of HIV-1 antibody and clinical assessment yielded transmission rates
      similar to those methods that incorporated virologic testing.

PMID- 7572940
TI  - The AIDS epidemic in India: a new method for estimating current human
      immunodeficiency virus (HIV) incidence rates.
AB  - Human immunodeficiency virus (HIV) incidence rates in India were estimated using
      a new method that accounts for follow-up bias. Follow-up bias arises in
      epidemiologic cohort studies when the incidence rate among individuals who do and
      do not return for follow-up are different. The new method combines data on the
      prevalence of p24 antigenemia among all those initially screened together with
      the longitudinal follow-up data on the subset of patients who returned for follow
      up. Using these methods, the current HIV incidence rate among patients attending
      sexually transmitted disease clinics in Pune, India, was 18.6% per year. It was
      found that follow-up bias can cause significant underestimation in HIV incidence
      rates, perhaps by as much as 60%. These incidence estimates, together with other
      HIV seroprevalence studies, suggest the HIV epidemic in India is growing rapidly.

PMID- 7572942
TI  - Repeat negative human immunodeficiency virus (HIV) testing in San Francisco:
      magnitude and characteristics.
AB  - The authors assessed the characteristics of repeat human immunodeficiency virus
      (HIV) testers at publicly funded sites in San Francisco. During 1992-1993, 31% of
      all HIV tests were performed on persons testing negative for the third time or
      more. Persons with greater numbers of prior negative tests were less likely to
      test HIV-positive. Repeat negative testers were more likely than first-time
      negative testers to be homosexual or bisexual males, homosexual or bisexual
      injection drug users (IDUs), or heterosexual IDUs. Repeat testers who
      seroconverted were more likely to be in these same transmission categories than
      repeat testers who remained negative. Because of the similarities in risk profile
      between those most likely to retest and those most likely to seroconvert,
      attempts to limit repeat testing must proceed cautiously.

PMID- 7572943
TI  - Exploration of simple insulin sensitivity measures derived from frequently
      sampled intravenous glucose tolerance (FSIGT) tests. The Insulin Resistance
      Atherosclerosis Study.
AB  - Both abnormal insulin levels and low insulin sensitivity have been implicated as
      risk factors for Type II diabetes mellitus and cardiovascular disease. While
      insulin level is relatively simple to assess, direct measurement of insulin
      sensitivity is much more invasive, costly, and time-consuming. The authors
      considered eight previously described measures or indices of indices of insulin
      sensitivity derived from the frequently sampled intravenous glucose tolerance
      test (FSIGT). Each one was evaluated by strength and consistency of association
      with insulin sensitivity computed from glucose clamp (SI(clamp)), across three
      glucose tolerance groups, including participants with normal glucose tolerance (n
      = 11), impaired glucose tolerance (n = 20), and non-insulin-dependent diabetes
      mellitus (n = 24). Minimal model analysis (MINMOD SI(22)), based on the 22-sample
      FSIGT, performed best based on statistical criteria of strong and consistent
      association with SI(clamp). An insulin sensitivity measure similar to that of
      Galvin et al. (Diabetic Medicine 1990;9:921-8), defined as glucose disappearance
      (10-50 minutes) divided by insulin area under the curve above baseline from 0-50
      minutes, performed best based on statistical criteria and time-savings. Galvin
      insulin sensitivity is simple to calculate, requires only a 50-minute FSIGT, and
      is significantly (p < 0.001) and not inconsistently (p = 0.12 for inconsistent
      association) associated with SI(clamp) over a wide range of glucose tolerance.

PMID- 7572944
TI  - Nutrition, latitude, and multiple sclerosis mortality: an ecologic study.
AB  - An epidemiologic study has been performed on the relation between the mortality
      rates from multiple sclerosis for the period 1983-1989 obtained for 36 countries,
      dietary fat, and latitude. By stepwise multiple regression analysis, saturated
      fatty acids, animal fat, animal minus fish fat, and latitude correlated
      independently and positively with multiple sclerosis mortality (p < 0.01-0.001
      for fat consumption, and p < 0.05-0.01 for latitude). The ratio of
      polyunsaturated fatty acids to saturated fatty acids (P/S ratio) and the ratio of
      unsaturated fatty acids (monounsaturated and polyunsaturated fatty acids) to
      saturated fatty acids (U/S ratio) correlated independently and negatively with
      multiple sclerosis mortality (p < 0.05-0.001). These findings support the
      hypothesis linking dietary fat intake and latitude to multiple sclerosis
      mortality.

PMID- 7572945
TI  - Associations of delta-aminolevulinic acid dehydratase genotype with plant,
      exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead
      workers.
AB  - Previous studies have suggested that polymorphisms in delta-aminolevulinic acid
      dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences
      in blood lead levels, perhaps due to differential binding of lead in
      erythrocytes. The authors examined associations of ALAD genotype with blood lead
      and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308
      currently exposed lead workers in three lead storage battery manufacturing plants
      in the Republic of Korea in 1993. The overall prevalence of the variant allele,
      ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in
      plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead
      levels, the allele was associated with blood lead levels greater than or equal to
      40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1
      6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and
      exposure duration) and with exposure durations greater than 6 years (adjusted OR
      = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among
      workers in plant C, the highest exposure plant, ALAD2 was associated with lower
      ZPP levels when controlling for blood lead levels. These data suggest that lead
      toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective
      for the health effects of lead. ALAD genotype also appears to have been a
      selection factor for current lead exposure status in the studied workers.

PMID- 7572946
TI  - Effect of risk factor values on lifetime risk of and age at first coronary event.
      The Adventist Health Study.
AB  - The effect of traditional coronary heart disease risk factors on lifetime risk,
      age at onset, and survival free of coronary disease has not been extensively
      studied. The authors have used the cohort data from 27,321 California Seventh-day
      Adventists who had no known heart disease in 1976 to investigate these questions.
      Multiple decrement life tables incorporating non-parametric estimates of
      conditional probabilities for both coronary disease and all other competing
      endpoints were used to estimate these survival outcomes. Variance estimators are
      provided in an appendix. Persons characterized by being either past smokers,
      diabetic, hypertensive, physically, non-vegetarian, or infrequent consumers of
      nuts often showed substantial differences in these survival outcomes.
      Statistically significant results include earlier age at onset of coronary
      disease at between 4 and 10 years, reduced life expectancy free of the disease
      between 5 and 9 years, and increased lifetime risk between 8% and 16%, when
      comparing groups with and without adverse values for different risk factors. The
      presence of adverse levels of two risk factors predicted even greater differences
      in these endpoints. These important effects are easily understood by the layman
      or non-epidemiologist professional, which is often not true of a relative risk.
      This should increase the effectiveness of such results when promoting behavioral
      change.

PMID- 7572948
TI  - Use of multiple reporting sources for perinatal hepatitis B surveillance and
      follow-up.
AB  - The New York State Perinatal Hepatitis B Prevention Program was implemented in
      New York State (excluding New York City) as a surveillance and control program in
      1988. This report describes and evaluates the program and provides data from 1991
      regarding hepatitis B surface antigen (HBsAg)-positive mothers and their infants'
      subsequent hepatitis B vaccination. The program was created using multiple
      existing surveillance and data collection systems. Completeness of case
      ascertainment was estimated by means of the Chandra Sekar-Deming method (J Am
      Stat Assoc 1949; 44:101-15). An audit of hospital medical records and follow-up
      by local health departments were used to validate reporting accuracy. Of 158,273
      live births in 1991, 363 (0.2%) were born to confirmed HBsAg-positive mothers.
      Estimated completeness of case-ascertainment was 96%. Thirty-five percent of
      HBsAg-positive mothers did not report risk factors for hepatitis B, confirming
      the need for universal testing. Of the infants, 83% received hepatitis B immune
      globulin and three doses of vaccine within one year of birth. By using existing
      data collection systems, the program was established quickly, and start-up
      funding and training requirements were simplified. Multiple reporting increased
      case-ascertainment to almost 100%. The program effectively identifies and ensures
      prompt vaccination of infants born to HBsAg-positive mothers.

PMID- 7572947
TI  - Impaired immune response to natural infection as a correlate of vaccine failure
      in a field trial of killed oral cholera vaccines.
AB  - In a field trial carried out in 1985 in Matlab, Bangladesh, the authors evaluated
      whether subjects who developed Vibrio cholerae 01 infections during the first
      year after earlier receipt of B subunit-killed whole cell (BS-WC) or killed whole
      cell-only (WC) oral cholera vaccines exhibited deficient serum vibriocidal immune
      responses to these infections. After severe V. cholerae 01 infections (n = 70) in
      subjects > 5 years of age, the age group in which both vaccines were efficacious,
      a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among
      vaccinees, compared with an 18.6 geometric mean-fold rise in placebo-recipients
      (p < 0.01). Depressions of serum vibriocidal responses among vaccinees were even
      more marked after asymptomatic infections (n = 30): a 1.1 geometric mean-fold
      rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients (p
      < 0.01). The authors conclude that subjects who failed to be protected by BS-WC
      and WC, despite being in the age group for which these vaccines were protective,
      exhibited poor immune responses even to the vigorous stimulus of natural
      infection. These findings raise the possibility that immune hyporesponsiveness
      may limit the potential efficacy attainable by cholera vaccines in populations
      with endemic cholera.

PMID- 7572949
TI  - Contraceptive methods and the risk of Chlamydia trachomatis infection in young
      women.
AB  - To evaluate the relation between contraceptive methods and cervical Chlamydia
      trachomatis infection, the authors studied a population-based sample of 1,779
      nonpregnant women aged 15-34 years who underwent cell culture diagnostic testing
      for the detection of C. trachomatis at a health maintenance organization. Barrier
      contraceptive method users were classified as those who reported using one of the
      following methods at time of testing: condom, diaphragm, cervical cap,
      spermicidal sponge, foam, or vaginal spermicidal suppositories. Barrier methods
      were associated with a reduction in the risk of chlamydial infection in women
      aged 25 years or older when compared with all other women in the same age
      category (adjusted prevalence odds ratio = 0.15, 95% confidence interval (CI)
      0.04-0.66). When compared with only noncontracepting women, the adjusted
      prevalence odds ratio was 0.34 (95% CI 0.06-1.99). The protective effect of
      barrier methods was not evident in women younger than age 25 years. Oral
      contraceptive use was not associated with the risk of C. trachomatis infection
      using either referent group; the adjusted prevalence odds ratio was 0.99 (95% CI
      0.57-1.73) compared with all other women, and 0.88 (95% CI 0.44-1.79) compared
      with noncontracepting women. These findings suggest that present patterns of use
      of barrier methods differ by age and afford only selective protection against
      cervical C. trachomatis infections.

PMID- 7572950
TI  - Re: "Point/counterpoint: meta-analysis of observational studies".

PMID- 7572952
TI  - Re: "When will nondifferential misclassification of an exposure preserve the
      direction of a trend?".

PMID- 7572951
TI  - Re: "When will nondifferential misclassification of an exposure preserve the
      direction of a trend?".

PMID- 7572953
TI  - Coping with the personal and professional frustrations of epidemiologic research.

PMID- 7572955
TI  - Association of education and income with estrogen receptor status in primary
      breast cancer.
AB  - The relation of education and income to the estrogen receptor status of primary
      breast tumors was studied using two patient groups. The first consisted of 887
      women from northeastern Ohio who were diagnosed between late 1974 and 1985 and
      entered into either of two prospective breast cancer clinical trials. All
      estrogen receptor values were determined by one laboratory. Through loglinear
      regression, patterns of association were studied among patient characteristics
      such as age, race/ethnicity, menopausal status, census tract indices of poverty
      and education, tumor diameter, stage of disease, obesity, and height and weight
      at the time of diagnosis. In this group of patients, estrogen receptor status was
      directly related to age, poverty, educational level, and tumor size. Younger
      women (odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.14-2.17), women
      from census tracts with greater poverty (OR = 1.77, 95% CI 1.28-2.44) or less
      education (OR = 1.98, 95% CI 1.43-2.73), and women with larger tumors (OR = 0.67,
      95% CI 0.48-0.92) were more likely to have estrogen receptor-negative tumors at
      the time of diagnosis of primary breast cancer. The second group consisted of 604
      patients from northeastern Ohio whose tumors were diagnosed between 1986 and mid
      1992 at University Hospitals of Cleveland. All estrogen receptor values were
      determined by one laboratory. Results from this second group of patients
      confirmed those from the first. This association of estrogen receptor-negative
      tumors with low economic and educational levels provides a potential explanation
      for the poor prognosis of these women.

PMID- 7572954
TI  - Long-term hormone replacement therapy and risk of breast cancer in postmenopausal
      women.
AB  - Despite extensive study, concerns remain about a possible association between
      long-term postmenopausal hormone treatment--particularly use of combination
      preparations--and risk of breast cancer. The authors evaluated the use of
      postmenopausal hormone replacement therapy in relation to breast cancer risk in a
      large multicenter, population-based case-control study. Women with a new
      diagnosis of breast cancer were identified through statewide tumor registries in
      Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly
      selected from population lists in each state. For this analysis of postmenopausal
      women, data were available from 3,130 breast cancer cases and 3,698 controls
      interviewed between 1989 and 1991. Replacement hormone use was not associated
      with breast cancer risk in women who had ever undergone this treatment (relative
      risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had
      used replacement hormones for 15 years or more, there was no clear increase in
      risk, although the small sample size did not preclude the possibility of a modest
      association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in
      combination with estrogens was similar to that in women using estrogens alone.
      Risk did not vary according to type of menopause, family history of breast
      cancer, history of benign breast disease, or alcohol intake. These results are
      consistent with the majority of reports which find no overall increased risk
      associated with the use of replacement hormones. However, in contrast to several
      other studies, this study did not find long-term use to be associated with
      increased risk. These results also do not support a hypothesized effect of
      combined progestin and estrogen use on the risk of breast cancer.

PMID- 7572956
TI  - System delay in breast cancer in whites and blacks.
AB  - Survival differences have been noted between black women and white women with
      breast cancer. It is hypothesized that a prolonged interval between initial
      medical consultation and establishment of a diagnosis (system delay), resulting
      in a more advanced stage of disease at diagnosis, might explain part of this
      survival difference. This study was performed to determine whether system delay
      differs between black and white breast cancer patients, and to examine predictors
      of delay in blacks and whites. The study population consisted of 996 female
      breast cancer patients from the National Cancer Institute's Black/White Cancer
      Survival Study, a cohort study carried out in 1985-1986 in the metropolitan areas
      of Atlanta, Georgia, New Orleans, Louisiana, and San Francisco/Oakland,
      California. The median system delay was slightly longer for blacks than for
      whites--2.7 weeks versus 2.1 weeks--but this difference was not statistically
      significant. Having a palpable lump at diagnosis was associated with reduced
      system delay in both races, while use of a public clinic increased system delay
      for blacks. Older women were less likely to be subject to longer system delay
      than younger women, and this effect was somewhat more pronounced in whites.
      Survival differences between blacks and whites are probably not due to
      differences in system delay. However, many women had delays of at least 3 months.
      Given that younger age and the absence of a palpable lump were the factors most
      predictive of significant system delay, interventions should be targeted
      specifically toward reducing system delay in younger women who present without
      the classical painless lump.

PMID- 7572957
TI  - Breast mammographic pattern: a concatenation of confounding and breast cancer
      risk factors.
AB  - A mammographic pattern of > 25% radiodensity is associated with increased risk
      for breast cancer. Mammographic pattern is influenced by age, body weight,
      reproductive factors, and race/ethnicity. The interaction among these factors in
      predicting breast radiographic pattern, and their association with the presence
      of histologic markers of increased risk of breast cancer, is poorly defined. To
      elucidate the relations among epidemiologic, radiographic, and histologic markers
      of breast cancer risk, the authors studied these factors in an unselected
      forensic autopsy series, accumulated between 1978 and 1983, of 486 women aged 15
      98 years at death. Older age and/or postmenopausal status was the strongest
      predictor of radiolucent breast pattern. Obesity, defined as a Quetelet index
      (weight(kg)/height(m)2) of > 25, and large breast size were also highly
      significant predictors of breast radiolucency. Factors related to parity were not
      significant predictors of breast parenchymal pattern. Native American race was an
      independent predictor of breast radiolucency in this population. A dense
      parenchymal pattern was associated with increased prevalence of marked cystic
      change and the presence of duct epithelial hyperplasia in women under age 35. The
      results support the association of breast radiodensity with ethnic/racial,
      reproductive, and histologic factors predictive of cancer risk. However, this
      association is overshadowed by the effects of obesity and aging or menopause.

PMID- 7572959
TI  - Baldness and coronary heart disease rates in men from the Framingham Study.
AB  - The authors assessed the relation between the extent and progression of baldness
      and coronary heart disease. Baldness was assessed twice, in 1956 and in 1962, in
      a cohort of 2,017 men from Framingham, Massachusetts. Extent of baldness was
      classified in terms of number of bald areas: no areas bald (n = 153), one area
      bald (n = 420), two areas bald (n = 587), and all areas bald (n = 857). Men who
      were assessed both times and who had two or fewer bald areas during the first
      evaluation were classified into one of three groups: "mild or no progression,"
      "moderate progression," or "rapid progression." The cohort was followed for up to
      30 years for new occurrences of coronary heart disease, coronary heart disease
      death, cardiovascular disease, and death due to any cause. The relations between
      the extent and progression of baldness and the aforementioned outcomes were
      assessed using a Cox proportional hazards model, adjusting for age and other
      known cardiovascular disease risk factors. Extent of baldness was not associated
      with any of the outcomes. However, the amount of progression of baldness was
      associated with coronary heart disease occurrence (relative risk (RR) = 2.4, 95%
      confidence interval (CI) 1.3-4.4), coronary heart disease mortality (RR = 3.8,
      95% CI 1.9-7.7), and all-cause mortality (RR = 2.4, 95% CI 1.5-3.8). Rapid hair
      loss may be a marker for coronary heart disease.

PMID- 7572958
TI  - The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in
      northern Manhattan, 1988-1993.
AB  - Sex and ethnic differences in the frequency of Parkinson's disease have become
      increasingly important, because putative genetic and environmental risk factors
      have been identified. The authors estimated the prevalence and incidence of
      Parkinson's disease in a culturally diverse community in New York City over a 4
      year period (January 1, 1988-December 31, 1991) using a disease registry
      substantiated, for older individuals, by a subsequent survey of a random sample
      of Medicare recipients between January 1, 1992, and December 31, 1993. The
      prevalence rate was 107 per 100,000 persons, and over a 3-year period the average
      incidence rate was 13 per 100,000 person-years. Age-adjusted prevalence rates
      were lower for women than for men in each ethnic group and were lower for blacks
      than for whites and Hispanics. Incidence rates were highest among black men, but
      they were otherwise comparable across the sex and ethnic groups. The estimated
      cumulative incidence of Parkinson's disease up to age 90 years was lower for
      women than for men, which could partially explain the lower prevalence rate. By
      ethnic group, the cumulative incidence was higher for blacks than for whites and
      Hispanics, but more deaths occurred among incident black cases. Discrepant
      prevalence and incidence rates of Parkinson's disease among blacks and women
      warrant further investigation. While selective mortality could partially account
      for this paradox, it is also possible that a delay in diagnosis due to limited
      access to appropriate health services among these individuals could have resulted
      in the observed discordant rates of disease.

PMID- 7572960
TI  - Marital status, change in marital status, and mortality in middle-aged British
      men.
AB  - The effects of marital status and change in marital status on mortality among
      middle-aged British men were examined in a prospective cohort study, the British
      Regional Heart Study. This is a nationally representative cohort of men selected
      at random from general medical practices in 24 towns in England, Wales, and
      Scotland. It comprises 7,735 men aged 40-59 recruited in 1978-1980 and followed
      up for 11.5 years. Marital status and a wide range of biologic and lifestyle
      variables were measured at screening, and changes in marital status were assessed
      after 5 years. Single (never-married) men had an increased risk of cardiovascular
      disease mortality (relative risk (RR) = 1.5, 95% confidence interval (CI) 1.0
      2.2) and noncancer, noncardiovascular mortality (RR = 1.8, 95% CI 1.1-3.3) after
      adjustment for potentially confounding variables: age, social class, smoking,
      recall of ischemic heart disease, recall of diabetes mellitus, use of
      antihypertensive drugs, body mass index, physical activity, alcohol intake,
      employment status, systolic blood pressure, blood cholesterol, and forced
      expiratory volume in 1 second. Divorced/separated men were not at increased risk
      of mortality, and widowed men were only at increased risk of other non
      cardiovascular disease mortality (RR = 2.4, 95% CI 1.1-5.3). There was no effect
      of marital status on cancer mortality. Men who divorced during the follow-up
      period were at increased risk of both cardiovascular disease mortality (RR = 1.9,
      95% CI 0.9-3.9) and other non-cardiovascular disease mortality (RR = 4.0, 95% CI
      1.5-10.6), but men who became widowed during this time were not at increased
      risk. The excess mortality among single and recently divorced men was not
      explained by poor health or by exposure to a wide range of risk factors. It is
      unlikely that selection bias, chance, or artifact is responsible for the general
      relation between marital status and mortality. Variable and incomplete control
      for confounding by socioeconomic status and risk factors for common diseases may
      explain some of the inconsistencies observed between studies and between
      different categories of unmarried men (i.e., never-married, widowed, and
      divorced). It is possible that the social support offered by marriage exerts a
      protective effect for some men.

PMID- 7572962
TI  - Biologic sex as a risk factor for Helicobacter pylori infection in healthy young
      adults.
AB  - Diseases associated with Helicobacter pylori infection, such as peptic ulcer
      disease and gastric cancer, afflict men more frequently than women. No study,
      however, has demonstrated any difference in sex-specific rates of H. pylori
      infection. In a healthy population undergoing multiphasic health evaluations in
      1992-1993 as members of the Kaiser Permanente Medical Care Program of Northern
      California, adults aged 20-39 years were screened for antibodies to H. pylori
      infection using a serum enzyme-linked immunosorbent assay and were surveyed with
      regard to their demographic characteristics and health practices. Among 556
      African-American, Hispanic, and white men and women, male sex was a significant
      risk factor for infection. Other risk factors included African-American race and
      Hispanic ethnicity, increasing age, living with children, birth in a developing
      country, and lower levels of income and education. Men consistently had a higher
      prevalence of antibodies across all strata of race/ethnicity, age, education, and
      income, and in multivariate analysis male sex remained significantly associated
      with infection (odds ratio = 2.0, 95% confidence interval 1.2-3.1). African
      American race, Hispanic ethnicity, increasing age, lower levels of education, and
      birth in a developing country were also associated with infection in multivariate
      analysis. Data from previously reported seroprevalence studies support a tendency
      for men to have a higher risk of infection. The higher prevalence of infection
      among young males as observed in Northern California may account in part for the
      increased incidence of H. pylori-related diseases among men in later decades of
      life.

PMID- 7572961
TI  - The role of universal distribution of vitamin A capsules in combatting vitamin A
      deficiency in Bangladesh.
AB  - Vitamin A deficiency is a major public health problem among preschool-aged
      children in many developing countries. In Bangladesh, a national nutritional
      surveillance system was initiated in 1990 to monitor 1) the occurrence of vitamin
      A deficiency by history of night blindness and 2) the routine coverage of
      national twice-yearly prophylactic vitamin A capsule (VAC) distribution. This
      study comprised data collected from June 1990 to August 1994. The VAC
      distribution had a mean coverage rate of 48.7% (95% confidence interval (CI) 48.4
      49.0) in the rural areas; the coverage rate in the urban slums was 93.7% (95% CI
      93.4-94.0). In the rural areas, the mean prevalence of night blindness was 0.86%
      (95% CI 0.81-0.91) and the bimonthly prevalence of night blindness ranged from
      0.50% (95% CI 0.32-0.77) to 1.48% (95% CI 1.19-1.85), while in the urban slums
      the mean prevalence was 0.22% (95% CI 0.18-0.28) and the bimonthly prevalence
      ranged from zero to 0.62% (95% CI 0.27-1.37). The efficiency of VAC distribution
      was 27% (95% CI 17.6-35.3) in the rural areas and 77.8% (95% CI 61.8-87.1) in the
      urban slums. After adjustment for multiple potentially confounding factors, VAC
      receipt by individual children reduced the risk of night blindness in both rural
      and urban areas (rural areas: odds ratio (OR) = 0.74, 95% CI 0.63-0.87; urban
      slums: OR = 0.39, 95% CI 0.19-0.82). Breastfeeding was a protective factor for
      night blindness in both rural (OR = 0.53, 95% CI 0.42-0.67) and urban (OR = 0.32,
      95% CI 0.15-0.66) areas. Night blindness was inversely related to the level of
      routinely attained coverage, and the degree of protection was associated with the
      time interval between the moment of VAC receipt and the moment of data
      collection. Although the prevalence of vitamin A deficiency in Bangladesh has
      been considerably lower in the 1990s than it was in the 1980s, it is still
      prevalent at all socioeconomic levels. Supplementation with high-dose VACs is an
      effective strategy for reducing night blindness, but the efficiency of the
      program will improve when coverage in the rural areas increases.

PMID- 7572963
TI  - Risk factors for human immunodeficiency virus seroconversion among out-of
      treatment drug injectors in high and low seroprevalence cities. The National AIDS
      Research Consortium.
AB  - From 1988 to 1991, 6,882 drug injectors in 15 US cities were interviewed and had
      serum samples collected. The interviews and samples were analyzed for
      determination of significant predictors of human immunodeficiency virus (HIV)
      seroconversion in the 10 low seroprevalence cities and the five high
      seroprevalence cities. The unit of analysis was the period of observation between
      consecutive paired interviews/blood samples. In Cox proportional hazards
      regression, significant predictors of seroconversion in the low seroprevalence
      cities were: not being in drug treatment, injecting in outdoor settings or
      abandoned buildings, using crack cocaine weekly or more frequently, engaging in
      woman-to-woman sex, being of non-Latino race/ethnicity, and city seroprevalence.
      Predictors in high seroprevalence cities were: injecting with potentially
      infected syringes, not being in drug treatment, and having a sex partner who
      injected drugs. These findings suggest that HIV may be concentrated in
      sociobehavioral pockets of infection in low seroprevalence cities. For reducing
      HIV transmission, these results suggest: 1) in low seroprevalence cities,
      localized monitoring to detect specific emerging sociobehavioral pockets of
      infection, and quick implementation of appropriate targeted interventions if
      necessary; 2) in high seroprevalence cities, relatively more emphasis on locality
      wide outreach and syringe-exchange projects to reduce risky behavior; and 3) in
      both types of cities, considerable expansion of drug treatment programs.

PMID- 7572964
TI  - A case-control study of human immunodeficiency virus type 1 seroconversion and
      risk-related behaviors in the Chicago MACS/CCS Cohort, 1984-1992. Multicenter
      AIDS Cohort Study. Coping and Change Study.
AB  - This paper focuses on 76 human immunodeficiency virus type 1 (HIV-1)
      seroconverters who concurrently participated in the Chicago, Illinois, component
      of the Multicenter AIDS Cohort Study (MACS) and the Coping and Change Study (CCS)
      of homosexual/bisexual men between 1984 and 1992. A nested case-control analysis
      was performed to assess the critical behavioral risk factors associated with
      incident HIV-1 infection and the consistency of these relations in early (1984
      1988) versus later (1989-1992) phases of the study. Univariate results revealed
      strong early period associations between seroconversion and various measures of
      receptive anal intercourse (RAI) that became considerably weaker in the study's
      later period. The weaker associations reflected the overall decline in levels of
      RAI among the cohort during the 9 years of observation. In contrast, univariate
      results revealed stronger later period associations between seroconversion and
      measures of receptive oral intercourse and insertive anal intercourse. Subsequent
      multivariate testing did not support the hypothesis that receptive oral
      intercourse and/or insertive anal intercourse have replaced unprotected RAI as
      important risk behaviours in the homosexual transmission of HIV-1. In conditional
      logistic regression models combining intercourse measures with indices of drug
      and condom use, only the latter variables were consistently associated with HIV-1
      seroconversion in both early and later study periods. Adjusted odds ratios (ORs)
      for nonuse of condoms during RAI were consistently significant throughout the
      study (ORs = 3.7-4.8), while adjusted odds ratios for recreational drug use
      variables rose dramatically during the latter half of the study (e.g., for use of
      cocaine, OR = 81.3 (95% confidence interval 8-824) [corrected], and for use of
      nitrite "poppers," OR = 9.1 (95% confidence interval 1.8-45.5)). The behavioral
      intervention applications of these findings, as well as their relation to data
      from other recent cohort studies of HIV-1 seroconversion among
      homosexual/bisexual men, are discussed.

PMID- 7572965
TI  - Re: "Case-control study of residential radon and lung cancer in Winnipeg,
      Manitoba, Canada".

PMID- 7572967
TI  - Re: "Cancer risks associated with occupational exposure to magnetic fields among
      electric utility workers in Ontario and Quebec, Canada, and France: 1970-1989".

PMID- 7572966
TI  - Case-cohort analysis of case-coverage studies of vaccine effectiveness.
AB  - Evaluation of vaccine field effectiveness may be performed by combining
      surveillance data on incident cases with an immunization coverage survey.
      Although many methods have been used for the analysis of studies of similar
      design, they are not always desirable or optimal. The authors discuss these
      approaches and propose use of a case-cohort analysis for such a study design when
      appropriate. The case-cohort analytic approach is illustrated with data from
      studies of a vaccine for Haemophilus influenzae type b (Hib) disease in children
      living on a southwestern Native American reservation during 1988-1993.

PMID- 7572968
TI  - Re: "Invited commentary: a critical look at some popular meta-analytic methods".

PMID- 7572969
TI  - Physical activity as an index of heart attack risk in college alumni. 1978.

PMID- 7572970
TI  - Multiple comparisons and related issues in the interpretation of epidemiologic
      data.

PMID- 7572971
TI  - Height and the risk of cardiovascular disease in women.
AB  - Height has been inversely associated with coronary heart disease in several
      prospective studies in men, but data in women are sparse. The relation between
      height and cardiovascular disease was examined in 14 years of follow-up data from
      the Nurses' Health Study, a prospective cohort of 121,700 US female nurses aged
      30-55 years in 1976. The relative risks associating height with coronary heart
      disease (nonfatal myocardial infarction (n = 1,000), fatal myocardial infarction
      (n = 304), confirmed angina (n = 1,343), or coronary revascularization (n = 901))
      were estimated after adjustment for a large number of cardiovascular risk
      factors, including age and body mass index. Compared with the shortest women (<
      or = 61 inches (< or = 1.55 m)), the relative risk of coronary heart disease was
      0.82 (95% confidence interval (CI) 0.73-0.92) for women 62-63 inches (1.57-1.60
      m) tall, 0.74 (95% CI 0.65-0.85) for women 64 inches (1.63 m) tall, 0.79 (95% CI
      0.70-0.89) for women 65-66 inches (1.65-1.68 m) tall, and 0.73 (95% CI 0.65-0.83)
      for women 67 or more inches (> or = 1.70 m) tall (p for trend < 0.0001). The
      inverse association was more pronounced for angina/coronary revascularization (p
      for trend < 0.0001; relative risk for 67 or more inches = 0.67 (95% CI 0.58
      0.78)) than for myocardial infarction (p for trend = 0.03; relative risk for 67
      or more inches = 0.78 (95% CI 0.64-0.95)). No trend was evident for height in
      relation to risk of stroke. These data support the hypothesis that height is
      inversely related to risk of coronary heart disease in women.

PMID- 7572972
TI  - Prediction of adult cardiovascular multifactorial risk status from childhood risk
      factor levels. The Bogalusa Heart Study.
AB  - There is increasing interest in identifying children at risk for later
      development of cardiovascular disease. The authors studied 1,457 children who
      were first examined as part of the Bogalusa Heart Study in 1973 and again 15
      years later as young adults. Age-, race-, and sex-specific quartiles were defined
      for each of three risk factor variables-ponderal index (weight/height3), systolic
      blood pressure, and cholesterol--for both the child and adult measures. Adults
      were classified as clustered if they were in the top quartile for each of the
      variables. Clustered adults had higher levels of several risk factor variables,
      in addition to the criteria variables, than did nonclustered individuals. Of
      children who placed in the top quartile on three factors, 21.8% were clustered as
      adults. Only 1.1% of those with no risk factor levels in the top quartile were
      clustered as adults (p < 0.0001). Logistic regression was used to predict adult
      cluster status from childhood variables levels. All three factors were
      significant predictors, with blood pressure being the most powerful. This well
      fitting model is easily interpretable in terms of standard deviations and can be
      a useful model for identifying at-risk children.

PMID- 7572974
TI  - Epidemiologic association between dietary calcium intake and blood pressure: a
      meta-analysis of published data.
AB  - The objectives of the study were to assess whether the epidemiologic data support
      a relation between dietary calcium intake and blood pressure, to obtain a
      quantitative estimate of the difference in blood pressure for a given difference
      in dietary calcium intake, and to assess the public health implications. A meta
      analysis of published data (January 1983 to November 1993) that investigated the
      association between dietary calcium intake and blood pressure in different
      populations around the world was performed. Of 63 population studies identified,
      23 were suitable for a quantitative overview (total n = 38,950). Unadjusted
      regression coefficients (95% confidence intervals) were obtained. Pooled
      unadjusted regression coefficients (95% confidence intervals) were then computed
      weighting each individual study by the inverse of its variance. Tests of
      heterogeneity and sensitivity analysis were carried out, and the possibility of
      publication bias was assessed. The regression coefficients ranged between -9.40
      and 1.63 mmHg/100 mg calcium for systolic blood pressure and between -4.90 and
      0.47 for diastolic blood pressure. In men (11 studies, n = 7,271), the pooled
      regression coefficients were -0.010 and -0.009 mmHg/100 mg calcium for systolic
      and diastolic pressures, respectively (p < 0.001 and p < 0.05). In women (six
      studies, n = 8,507), they were -0.15 and -0.057 mmHg/100 mg calcium (p < 0.001
      and p < 0.02), and in men and women combined (six studies, n = 23,172 for
      systolic pressure and four studies, n = 3,215 for diastolic pressure) they were 
      0.061 and -0.061 mmHg/100 mg calcium (p < 0.001 and p < 0.05). In those studies
      that used the 24-hour recall method, the pooled regression coefficients were 
      0.06 and -0.09 mmHg/100 mg calcium (p < 0.005 and p = 0.07), whereas in those
      that used the food frequency questionnaire, they were -0.15 and -0.05 mmhg/100 mg
      calcium (p < 0.001 and p < 0.03). These data are consistent with an inverse
      association between dietary calcium intake and blood pressure. However, the size
      of the estimate, the observed heterogeneity among studies, and the possibility of
      confounding and publication bias indicate that an increase in calcium intake
      above the Recommended Dietary Allowance is not recommended at population level
      for the prevention and treatment of high blood pressure.

PMID- 7572973
TI  - Relation of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to
      cardiovascular risk factors in postmenopausal women.
AB  - Sex hormones play a major role in determining the risk of cardiovascular disease.
      While several studies have shown that reduced sex hormone-binding globulin is
      associated with an atherogenic pattern of lipoproteins and increased glucose
      concentrations in premenopausal women, little data are available examining the
      association of sex hormone-binding globulin and sex hormones with cardiovascular
      risk factors in postmenopausal women, a group with high rates of cardiovascular
      disease. The investigators hypothesized that in postmenopausal women decreased
      sex hormone-binding globulin and increased testosterone would be associated with
      an atherogenic pattern of cardiovascular risk factors. The sex hormone-binding
      globulin, total and free testosterone, estrone, and dehydroepiandrosterone
      sulfate (DHEA-SO4) in 253 postmenopausal women who were not taking hormones were
      measured in a population-based study, the Beaver Dam Eye Study (Beaver Dam,
      Wisconsin, 1988-1990). Sex hormone-binding globulin was significantly inversely
      correlated with body mass index (r = -0.53, p 0.001), glycosylated hemoglobin (r
      = -0.34, p < 0.001), and diastolic blood pressure (r = -0.25, p < 0.001), and
      positively correlated with high density lipoprotein cholesterol (HDL cholesterol)
      (r = 0.31, p < 0.001), and HDL cholesterol/total cholesterol (r = 0.31, p <
      0.001). Total (r = -0.20, p < 0.01) and free (r = -0.14, p < 0.05) testosterone
      were significantly inversely correlated with HDL cholesterol/total cholesterol
      ratio. Total testosterone concentrations were also significantly positively
      correlated with total cholesterol (r = 0.15), body mass index (r = 0.16), and
      systolic (r = 0.17) and diastolic (r = 0.18) blood pressures (all p < 0.01). DHEA
      SO4 was not associated with any of the metabolic variables, while estrone was
      inversely associated only with the HDL cholesterol/total cholesterol ratio (r =
      0.13, p < 0.05). The authors conclude that increased androgenization in
      postmenopausal women is associated with atherogenic changes in cardiovascular
      risk factors.

PMID- 7572975
TI  - Tracking of blood pressure over a 40-year period in the University of Manitoba
      Follow-up Study, 1948-1988.
AB  - High blood pressure is a well-recognized, modifiable, cardiovascular disease risk
      factor. Tracking of blood pressure was examined in the University of Manitoba
      Follow-up Study, a cohort of 3,983 men followed over a 40-year period, between
      1948 and 1988. Blood pressure measurements recorded over time in these men, prior
      to the development of ischemic heart disease, were used in this analysis. Two
      approaches to tracking were used; correlation analysis and the quantification of
      the likelihood for a man whose blood pressure was in either the top or bottom
      quintile to remain in the extreme end of the distribution at later measurement.
      For ages 25-75 years and for intervals between blood pressure measurement ranging
      from 5 to 35 years, significant evidence for tracking was found. The strongest
      evidence for tracking was in middle age, 45-55 years. Strength of tracking
      decreased with increasing time between measurements. This analysis suggests that
      men at highest risk for hypertension can be identified at a young age. Hence,
      strategies for prevention of cardiovascular complications can be targeted in
      early adulthood.

PMID- 7572977
TI  - Case-control study of digital-rectal screening in relation to mortality from
      cancer of the distal rectum.
AB  - The authors conducted a case-control study to examine the benefit of digital
      rectal examination in reducing mortality from distal rectal cancer. The Kaiser
      Permanente Medical Care Program provides prepaid medical services to
      approximately 30 percent of the residents in its northern California service
      area. Members of the program aged 45 years and over who were diagnosed with fatal
      cancer of the distal rectum during the period 1971-1986 and who died before 1988
      as a result of their cancer (n = 172) and matched controls were selected for the
      study. Information on digital-rectal examinations received in the absence of
      recorded symptoms during the 10 years prior to the diagnosis date of the case was
      obtained from medical charts. Similar proportions of cases (20.9%) and controls
      (23.3%) had been screened during the year before the diagnosis of the case
      (adjusted odds ratio = 0.96, 95% confidence interval 0.56-1.7) and during longer
      intervals throughout the 10 years before the diagnosis date of the case. These
      results suggest no efficacy of digital-rectal examination for preventing
      mortality from rectal cancer, although a modest effect cannot be ruled out.

PMID- 7572976
TI  - Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a
      prospective cohort study of postmenopausal women.
AB  - Very few prospective studies have reported previously on the association of
      micronutrient intake and the risk of cancers of the upper digestive tract (mouth,
      pharynx, esophagus, and stomach) in western populations. During 7 years of follow
      up in the Iowa Women's Health Study, from 1986-1992, 59 of the 34,691 at-risk
      cohort members developed cancers of the upper digestive tract. The association of
      retinol and antioxidant vitamins (carotene and vitamins C and E) were evaluated
      separately for cancers of the mouth/pharynx/esophagus (n = 33) and stomach (n =
      26). After adjustment for age, smoking, and total energy intake, higher intakes
      of carotene and vitamins C and E were related to lower risks of both
      oral/pharyngeal/esophageal and gastric cancers, while retinol was associated with
      lower risk of gastric cancer only. The dose-response relation between gastric
      cancer risk and intake of carotene was clear and statistically significant, with
      relative risks of 0.6 and 0.3, respectively, observed among women in the upper
      two versus the lowest tertiles of intake. This study provides further evidence
      that higher intake of antioxidant vitamins may be important in the prevention of
      cancers of the upper digestive organs.

PMID- 7572978
TI  - Association between family history of benign prostatic hyperplasia and urinary
      symptoms: results of a population-based study.
AB  - Baseline measurements for a population-based prospective cohort study were used
      to assess the association between family history of enlarged prostate and urinary
      symptoms. Between December 1989 and March 1991, a group of randomly selected men
      aged 40-79 years from Olmsted County, Minnesota, was administered a previously
      validated questionnaire that included questions with wording close to that of the
      American Urological Association's Symptom Index. A detailed family history of an
      enlarged prostate was obtained by personal interview, and peak urinary flow rates
      were measured for each participant. Of the 2,119 men, 440 (21 percent) reported a
      family history of an enlarged prostate. The age-adjusted odds of having moderate
      or severe urinary symptoms were elevated among those with a family history
      relative to those without (odds ratio = 1.3, 95 percent confidence interval 1.1
      1.7). With simultaneous control for effects of age and worry about urologic
      function, the odds ratio remained at 1.3 (95 percent confidence interval 1.0
      1.6). Furthermore, this risk was greater for men with relatives diagnosed at a
      younger age (odds ratio = 2.5, 95 percent confidence interval 1.5-4.3). Men with
      a family history were also 1.3 times as likely to have an impaired peak urinary
      flow rate. These findings suggest that men with a family history of an enlarged
      prostate may be at increased risk for development of symptoms and signs
      suggestive of benign prostatic hyperplasia and that this risk is greater in men
      with relatives diagnosed at a younger age. Recognition of this association may
      help to target early interventions and may lead to further clues about the causes
      of benign prostatic hyperplasia.

PMID- 7572979
TI  - Case-control study of the effectiveness of different types of helmets for the
      prevention of head injuries among motorcycle riders in Taipei, Taiwan.
AB  - A total of 1,351 victims of motorcycle accidents, brought to one of 15 hospitals
      responsible for emergency care in Taipei, Taiwan, between August 1 and October
      15, 1990, were enrolled in a case-control study to investigate the effectiveness
      of different types of helmets for the prevention of head injuries. A total of 562
      of those with head injuries were assigned to the case group, while the remaining
      789 victims without head injuries were considered as emergency room controls. The
      case group was subdivided into daytime and evening cases, according to the time
      of accident. For each daytime case, we took four pictures of passing motorcycles
      at the same time and place during the week after each accident. Of the 254
      daytime cases, we successfully took pictures for 224 (88%) and identified 1,094
      motorcycle riders in the pictures as street controls. Logistic regression
      analyses were used to determine the roles of the following variables in
      predicting risk of head injury: age, sex, riding position, weather, place of
      accident, helmet type, and motorcycle type, and status of helmet wearing. The
      relative risk of head injury among motorcycle riders was significantly reduced by
      wearing a full-face helmet, but not by wearing a full- or a partial-coverage
      helmet.

PMID- 7572980
TI  - Preschool physical activity level and change in body fatness in young children.
      The Framingham Children's Study.
AB  - This study examined the effect of preschool physical activity on the change in
      body fatness from preschool to first grade. The Framingham Children's Study, a
      longitudinal study of childhood cardiovascular risk behaviors, began in 1987 with
      the enrollment of 106 children aged 3-5 years and their parents. The present
      analyses include 97 healthy children with complete data from study entry into
      first grade. Physical activity was assessed twice yearly for 5 days with an
      electronic motion sensor. The authors estimated change in the child's level of
      body fat from preschool to first grade by using the slopes of triceps and
      subscapular skinfolds and body mass index. On average, active girls (i.e., those
      with above-median activity levels) gained 1.0 mm in their triceps skinfolds from
      baseline to first grade, while inactive girls gained 1.75 mm. Active boys lost an
      average of 0.75 mm in their triceps, while inactive boys gained 0.25 mm. When
      age, television viewing, energy intake, baseline triceps, and parents' body mass
      indices were controlled for, inactive preschoolers were 3.8 (95% confidence
      interval 1.4-10.6) times as likely as active preschoolers to have an increasing
      triceps slope during follow up (rather than a stable or decreasing slope). This
      relative risk estimate was slightly higher for children with more body fat at
      baseline. In this study, preschool-aged children with low levels of physical
      activity gained substantially more subcutaneous fat than did more active
      children.

PMID- 7572981
TI  - Physical activity assessment using a pedometer and its comparison with a
      questionnaire in a large population survey.
AB  - The aim of this study was to evaluate the use of the pedometer in epidemiologic
      research on physical activity. Within the framework of a health examination
      survey in 1988-1989, physical activity was assessed in a representative
      population sample of 493 men and women aged 25-74 years who were residents of
      Switzerland. They wore a pedometer for 1 week at work and during leisure time,
      and the results, converted into steps per day, were compared with answers to a
      questionnaire. The average number of steps per day decreased from 11,900 to 6,700
      and from 9,300 to 7,300 for men and women, respectively, in the youngest to the
      oldest age groups. For men, categorized according to type of physical activity at
      work, there was a highly significant difference in the number of steps (p <
      0.001), whereas in women the results were associated with leisure-time physical
      activity (p = 0.003). For both sexes, practicing sports more than once a week was
      associated with an important increase in steps per day. Analyzing the number of
      steps according to the day of the week and occupational category produced an
      unexpected result: Men with a physically active job engaged in more leisure-time
      physical activity on the weekend. The pedometer proved to be useful in assessing
      physical activity in a large, free-living population.

PMID- 7572982
TI  - Passive and active maternal smoking during pregnancy, as measured by serum
      cotinine, and postnatal smoke exposure. I. Effects on physical growth at age 5
      years.
AB  - The authors evaluated the effect of maternal environmental tobacco smoke (ETS)
      exposure during pregnancy and prenatal maternal smoking on child's height at age
      5 years, using serum cotinine as a biomarker of exposure. They also determined
      the effects of postnatal smoke exposure. Participants included 2,622 women
      enrolled in the Child Health and Development Studies between 1964 and 1967.
      Nonsmokers were divided into ETS-exposed (serum cotinine 2-10 ng/ml; n = 77) and
      not exposed (n = 1,610), and smokers (n = 935) were divided into tertiles based
      on serum cotinine levels: 0-79, 80-163, and 164-569 ng/ml. Multivariate models
      adjusting for race, sex, birth order, and maternal height, body mass, education,
      and age indicated that children of smokers were 0.3, 0.3, and 0.8 cm shorter in
      the lowest, middle, and highest tertile of serum cotinine, respectively, and
      children of ETS-exposed women were 0.5 cm taller than those of nonsmokers. Only
      the children of heavy smokers were significantly shorter than children of
      nonsmokers; however, this difference disappeared after controlling for birth
      weight and gestational age. The adjusted heights of children of women who smoked
      both during and after pregnancy were significantly shorter than those of children
      of nonsmokers, but this effect also disappeared after controlling for birth
      weight and gestational age. These results suggest that the effects of smoke
      exposure on children's height may be explained by the effects of maternal smoking
      on fetal growth.

PMID- 7572983
TI  - Passive and active maternal smoking during pregnancy, as measured by serum
      cotinine, and postnatal smoke exposure. II. Effects on neurodevelopment at age 5
      years.
AB  - The authors sought to determine the neurobehavioral effects of prenatal exposure
      to maternal active smoking and environmental tobacco smoke (ETS), assessed by
      maternal serum cotinine level, and of postnatal exposure to smoke based on
      maternal report. Five-year-old children (n = 2,124) who were participants in the
      Child Health and Development Studies in Oakland, California, between 1964 and
      1967 were evaluated with the use of the Peabody Picture Vocabulary Test (PPVT)
      and the Raven Coloured Progressive Matrices Test, and also assessed on a
      behavioral rating scale completed by the mother that included questions on
      activity level. Children of ETS-exposed women did not differ from children of
      other nonsmokers on neurobehavioral assessment. Children whose mothers smoked
      during pregnancy had somewhat higher adjusted Raven (p = 0.10) and PPVT scores (p
      = 0.06) than children of nonsmokers, although they did not differ in their
      activity level (p = 0.32). However, children smoke-exposed during childhood did
      have lower adjusted Raven (p = 0.01) and PPVT scores (p = 0.16), and were rated
      more active by their mothers (p = 0.04). These differences may be attributed to
      uncontrolled confounding of sociobehavioral variables. However, the authors
      cannot rule out the possibility that ETS exposure during childhood may be more
      hazardous to neurodevelopment than prenatal exposure.

PMID- 7572984
TI  - A new perspective on John Snow's communicable disease theory.
AB  - When John Snow undertook the studies of the cholera epidemic of 1854 in London,
      he was testing his theory of communicable disease, which had been enunciated in
      an oration delivered at the 80th anniversary of the Medical Society of London.
      Snow had been elected orator of the year for 1853 and, according to his
      biographer, had spent the better part of a year in preparation. The oration was
      titled, "On Continuous Molecular Changes, More Particularly in Their Relation to
      Epidemic Diseases." Although the text of this oration is readily available in the
      1936 Commonwealth Fund facsimile reprint of Snow's more famous cholera studies,
      few modern epidemiologists are familiar with the work. In it, Snow lays out a
      theory which includes recognition that for each communicable disease there is a
      distinct and specific cause, that the causal agent is a living organism which is
      stable over many generations of propagation, that infection is necessary for
      communication to occur, and that the quantity of infectious material transmitted
      is increased by multiplication after infection to produce disease manifestations.
      Although Snow's theory is similar to Jacob Henle's formulations of a decade
      earlier, it is more precise, more comprehensive, and more explicit. On the basis
      of this work alone, Snow deserves broader recognition than he has received.

PMID- 7572985
TI  - Effect of United States residence on birth outcomes among Mexican immigrants: an
      exploratory study.
AB  - Adverse pregnancy outcomes such as low birth weight are increased among US-born
      mothers of Mexican descent compared with immigrant mothers born in Mexico. It is
      unknown whether adverse reproductive outcomes change among Mexican immigrants
      after only 5 years of US residence. The authors conducted a study of 1,114
      Mexican immigrant mothers and their infants in two California counties. The
      relation between US residence status and birth outcomes was examined, controlling
      for sociodemographic factors and maternal behaviors. Long-term immigrants who
      have lived in the United States for more than 5 years were more likely to deliver
      preterm infants (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.3) and
      low birth weight infants (OR = 1.5, 95% CI 0.8-2.7) than newcomers who have lived
      in the United States for 5 years or less. Long-term immigrants had higher parity,
      more pregnancy complications, and fewer planned pregnancies, and were more likely
      to smoke than newcomers. After controlling for confounders, the effect of
      residence status on preterm delivery was of borderline significance (adjusted OR
      = 1.8, 95% CI 1.0-3.2). Pregnancy complications was an intervening variable
      between residence status and preterm delivery. Length of US residence is
      associated with an increase in low birth weight via a decrease in gestational age
      rather than intrauterine growth retardation.

PMID- 7572986
TI  - Case-control study of risk factors for incident Lyme disease in California.
AB  - To identify risk factors for incident Lyme disease in California during the
      period June 1, 1991 to December 31, 1992, the authors compared the activities of
      101 cases of physician-diagnosed erythema migrans ascertained via both active and
      passive surveillance with those of 107 controls matched on sex, age, and
      neighborhood. Questions asked by telephone pertained to location of home,
      presence of wildlife around the house, hours of outdoor work and outdoor leisure
      activities, pet ownership, precautionary measures to avoid tick bites, tick
      removal methods, and knowledge about Lyme disease. For cases, activities
      pertained to the month prior to the onset of erythema migrans; controls were
      interviewed about the same activities during the same one-month period. The
      observation of deer and lizards around the home and a history of exposure to
      ticks were associated with Lyme disease (deer, odds ratio (OR) = 2.53, 95%
      confidence interval (CI) 1.25-5.15; lizards, OR = 2.14, 95% CI 1.14-4.04).
      However, the only activity associated with Lyme disease was the use for more than
      5 hours per week of wide maintained trails (OR = 11.33, 95% CI 1.33-123.5); this
      association occurred only in persons with other outdoor leisure activities. No
      other behaviors or activities were identified as risk factors for acquisition of
      Lyme disease in California.

PMID- 7572987
TI  - Internal validity analysis: a method for adjusting capture-recapture estimates of
      prevalence.
AB  - The authors propose a method for adjusting results of log-linear multi-source
      capture-recapture estimates of total population. The method compares the totals
      in some subpopulations of known size with estimates derived from various capture
      recapture approaches to these subpopulations. The authors term such an approach
      an "internal validity analysis". Trends in the ratios of the estimates to the
      known true values of these subpopulations provide a plausible indicator of the
      bias of some types of estimates of the total population especially when
      underlying assumptions of the methods used have not been met in analysis of the
      total population. The authors apply this method to published data on an open
      population of injection drug users that had been previously analyzed with a
      standard capture-recapture analysis as if it were a closed population. Internal
      validity analysis suggests that the size of this population is about 15% greater
      than that previously estimated.

PMID- 7572989
TI  - Steroid-responsive pulmonary disorders associated with myelodysplastic syndromes
      with der(1q;7p) chromosomal abnormality.
AB  - We report three patients with pulmonary disorders associated with myelodysplastic
      syndromes (MDS). All three patients had symptoms of pyrexia and respiratory
      discomfort. One patient had pulmonary eosinophilia with bilateral pleural
      effusion, one had interstitial pneumonia, and one had bilateral pleural effusion
      caused by systemic vasculitis. Elevated C-reactive protein (CRP) levels,
      polyclonal hypergammaglobulinemia, and morphological abnormalities in peripheral
      blood were observed in all three patients. The bone marrow of these patients
      revealed trilineage dysplasia and eosinophilia. Cytogenetic analysis showed
      [46,XY,-7,+der(1q;7p)]. Antibiotic treatment was not effective. However,
      improvement was dramatic after corticosteroid treatment; CRP levels were reduced
      and the hypergammaglobulinemia was improved. These cases suggest that MDS with [
      7,+der(1q;7p)] may be correlated with bone marrow eosinophilia and that an
      immunologic abnormality may be involved in the pulmonary disorders.

PMID- 7572988
TI  - EDTA-dependent pseudothrombocytopenia: a clinical and epidemiological study of
      112 cases, with 10-year follow-up.
AB  - In the past 10 years, we have observed 112 cases of EDTA-dependent
      pseudothrombocytopenia (PTCP) due to in vitro platelet clumping at room
      temperature. 93 patients had antiplatelet antibodies (48 IgM, 30 IgG, 3 IgA, and
      12 had two different isotypes concomitantly). In 20% of patients, the presence of
      IgM antibodies characteristically accompanied platelet agglutination also at 37
      degrees C, and in citrated blood. The phenomenon was not age or sex related, nor
      was it associated with any particular pathology or use of specific drugs, and was
      present in both healthy subjects and patients with various diseases. Flow
      cytofluorimetric analysis of CD5-positive B cells, which are responsible for
      autoantibody production, did not demonstrate any changes in the percentage and
      absolute number of this lymphocyte subset. Average follow-up was 5 years (6
      months-10 years); however, previous clinical records disclosed that PTCP was
      present for more than 15 years in four cases, and more than 20 years in three
      others, with no clinical manifestation of disease. This study confirms that EDTA
      dependent PTCP is a phenomenon related to the presence of natural autoantibodies
      with antiplatelet activity, devoid of pathological significance. Its clinical
      interest resides in the need for its prompt and certain recognition in order to
      avoid unnecessary examinations and therapeutic interventions. The best and most
      rapid technique for obtaining accurate platelet counts in PTCP subjects is to
      collect and examine EDTA blood at 37 degrees C; however, clumping will still be
      present in about 20% of these cases, and even in citrated blood. To obviate this
      phenomenon, blood should be collected in ammonium oxalate, and platelets counted
      in a Burker chamber.

PMID- 7572993
TI  - Hydroxyurea: an alternative to transfusion therapy for stroke in sickle cell
      anemia.

PMID- 7572990
TI  - Autologous bone marrow transplantation versus chemotherapy in relapsed/refractory
      non-Hodgkin's lymphoma: estimates of long-term survival from the recent
      literature.
AB  - Long-term survival following chemotherapy or autologous bone marrow
      transplantation in adults with relapsed/refractory non-Hodgkin's lymphoma was
      evaluated. English language articles published from January 1, 1988 to September
      1, 1993 were obtained from a broad-based MEDLINE search retrieving 3,854
      citations regarding therapy for lymphomas. Citations were evaluated using both
      computer-based evaluation and manual review. Articles were included if they
      addressed the disease of interest (non-Hodgkin's lymphoma, Working Formulation D
      H), the population of interest (adults with either relapsed or refractory
      disease), and the therapies of interest (chemotherapy or autologous bone marrow
      transplantation). Articles were excluded if they did not provide convincing
      information on long-term survival (as evidenced by either survival analysis or
      individual patient data) or if they reported a small number of patients (N < 15).
      No randomized trials of the two therapies were found. Nine case series were found
      reporting on 444 eligible patients receiving chemotherapy; eight were found
      reporting on 256 patients undergoing autologous marrow transplantation. After
      weighting by sample size, the mean 3-year survival rate was 25% (95% CI, 20-30%)
      following chemotherapy and 40% (95% CI, 33-47%) following marrow transplantation.
      The reporting of potentially relevant prognostic factors was inconsistent among
      articles. Despite our comprehensive synthesis and evaluation of currently
      available data, the survival advantage of marrow transplantation in
      relapsed/refractory non-Hodgkin's lymphoma that we report must be viewed as
      tentative, given the limitations of the case series data. In addition,
      establishing the comparability of patients treated with these therapies is made
      more difficult by the inconsistent reporting of potentially relevant prognostic
      factors. The results of an international randomized trial of these two therapies
      is forthcoming and may address some of these shortcomings.

PMID- 7572992
TI  - Recognition of unusual presentation of natural killer cell leukemia.
AB  - Expansion of the natural killer (NK) subset of lymphocytes represents a rare
      leukemia phenotype with variations in clinical presentation, morphology, surface
      phenotype, and effector function. This paper reports on a 5-year-old male patient
      who had an unusual presentation of an NK cell leukemia that was initially
      diagnosed as neuroblastoma. A bone marrow (BM) aspirate showed clumps of
      undifferentiated cells with the following phenotype: CD56bright+, CD33dim+, CD45
      , CD2-, CD19-, CD16-, and CD57-. Cytochemistry was noncontributory. The patient,
      having failed to respond to conventional neuroblastoma chemotherapy, was
      subsequently diagnosed as having NK cell leukemia based on functional in vitro
      assays. The patient responded to acute lymphoblastic leukemia (ALL) chemotherapy
      but relapsed 4 weeks into treatment and eventually died 25 weeks after initial
      presentation. The cell surface phenotype observed is consistent with a rare NK
      cell subset, the biology of which has not been well defined. Freshly isolated BM
      cells killed K562 cells in a conventional 51Cr-release assay. Both interleukin-2
      (IL-2) and interferon-alpha (IFN-alpha) induced LAK activity against the Daudi
      cell line. IL-2 induced proliferation of the leukemic cells. TNF-alpha, IFN
      gamma, IL-6, IL-1ra, and TGF-beta levels were assessed and found to be
      concentrated in BM, in contrast to plasma samples. TNF-alpha was present at a
      high concentration in BM (150.9 pg/ml), probably a reflection of the associated
      disease pathology of severe bone pain and pyrexia. In summary, this paper details
      clinical and laboratory investigations of a leukemia of a rare NK cell subset.

PMID- 7572991
TI  - Inactivation of the DCC tumor suppressor gene in a B-cell lymphoma cell line with
      the alteration of chromosome 18.
AB  - A B-cell lymphoma cell line, designated KML-1, was established from pleural
      effusion of a patient with non-Hodgkin's lymphoma of large-cell type. The
      lymphoma arose in the pelvis and ran an aggressive clinical course. Chromosome
      analysis of the cell line exhibited a complex karyotype including the loss of
      chromosome 18. To evaluate the molecular events in the cell line that may be
      associated with the development of the lymphoma, we investigated the expression
      and/or alterations of several classes of human genes, including oncogenes, tumor
      suppressor genes, and cytokine genes. The expression of the DCC (deleted in
      colorectal cancer) gene, located on the chromosome 18q21, was extremely reduced
      in KML-1 cell line, as compared with that in a normal spleen tissue and other 4
      lymphoma cell lines by the reverse transcription-polymerase-chain-reaction (RT
      PCR) method. This finding suggests that inactivation of the DCC gene might play a
      role in the pathogenesis of the case of lymphoma.

PMID- 7572994
TI  - A new hemophilia B mutation in the propeptide region of the FIX gene.

PMID- 7572995
TI  - Clearance of PCR-detectable lymphoma cells from the peripheral blood, but not
      bone marrow after therapy with campath-1H.

PMID- 7572997
TI  - Successful allogeneic bone marrow transplantation in a patient with ATRA-induced
      pseudotumor cerebri.

PMID- 7572996
TI  - Modified ICSH method for demonstration of myeloperoxidase.

PMID- 7572998
TI  - Autoimmune-associated hemophagocytosis.

PMID- 7572999
TI  - Prolonged survival and probable cure in chronic myelogenous leukemia.

PMID- 7573000
TI  - Disappearance of factor VIII antibody after removal of primary colon
      adenocarcinoma.

PMID- 7573002
TI  - Hyperkalemic hyperchloremic metabolic acidosis in a patient with sickle cell beta
      thalassemia.

PMID- 7573003
TI  - Arthralgia as the initial manifestation of malignant lymphoma.

PMID- 7573001
TI  - Production of parathyroid hormone-related peptide in a patient with acute
      lymphocytic leukemia with extensive osteolytic lesions and hypercalcemia.

PMID- 7573005
TI  - Increasing mortality from thrombotic thrombocytopenic purpura in the United
      States--analysis of national mortality data, 1968-1991.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare disease and the epidemiologic
      features have been incompletely characterized. Because of the historically high
      case-fatality rate for TTP, we analyzed U.S. multiple cause-of-death mortality
      data with TTP listed on the death record for the period 1968-1991, in order to
      estimate the incidence of TTP, to characterize demographic features of the
      decedents, and to determine if trends in mortality correlate with findings from
      clinical studies showing improved survival in recent years. There were 4,523 TTP
      associated deaths during the 24-year study period. The annual age-adjusted
      mortality rate decreased initially and reached its lowest point at 0.4 per
      1,000,000 residents for the years 1970 through 1973, and then increased steadily
      to 1.1 during the last 4 years of the study period, 1988 through 1991. We
      estimate the current incidence of TTP to be approximately 3.7 cases per 1,000,000
      residents. Deaths were rare below the age of 20 years, but the age-specific
      mortality rate for those 20 years and older increased steadily with increasing
      age. Regardless of age, females were affected more often than males, and the
      overall female-to-male age-adjusted rate ratio was 1.9 (95% confidence interval
      (CI), 1.8 to 2.0). The greatest age-specific difference was between females and
      males in their twenties (rate ratio 3.2; 95% CI, 2.6 to 3.9). The mortality rate
      for blacks, and especially black females, was higher than the mortality rate for
      whites (black-to-white age-adjusted rate ratio 3.4; 95% CI, 3.2 to 3.6; black
      female-to-white female age-adjusted rate ratio 3.6; 95% CI, 3.3 to 3.9), although
      the majority of deaths were among whites (71.5%). Infection with the human
      immunodeficiency virus (HIV) or an HIV-related diagnosis was reported in 61
      (1.3%) decedents overall and in 51 (4.4%) decedents from 1988 through 1991. The
      TTP mortality rate has increased over time despite reports of significant
      improvement in survival associated with clinical use of plasma infusion and
      plasma exchange. This trend in mortality suggests that the incidence of TTP is
      increasing. Blacks, and black females in particular, are affected at a
      disproportionately high rate. The increased incidence of HIV infection and
      related disease may have contributed to some of the increase in TTP mortality in
      recent years, but it does not explain the majority of the increase, which began
      before the onset of the HIV epidemic.

PMID- 7573004
TI  - Coagulant proteins and thrombin generation in synovial fluid: a model for
      extravascular coagulation.
AB  - The coagulant content and thrombin generating potential of synovial fluid from
      patients with osteoarthritis were studied as a model of extravascular
      coagulation. The concentrations of individual coagulant proteins were partially
      correlated with their molecular weight. The levels of the very large coagulants
      factor V, factor VIII and von Willebrand factor antigen (vWF:ag) are less than 1%
      of the activities found in a normal pooled reference plasma while smaller
      coagulants including factors IX, XI and prothrombin range between 9 and 30%. The
      protease inhibitors antithrombin-III (AT-III) and Alpha-2 macroglobulin in
      synovial fluid were present at levels of 74% and 13% of plasma, higher than
      expected based on their molecular weights. Prothrombin was more rapidly activated
      by tissue thromboplastin than by aPTT reagent. The thrombin activity formed in
      synovial fluid decreased more rapidly than that formed in dilute plasma. The
      addition of recombinant factor VIII or bovine factor V to synovial fluid
      accelerated the thrombin production by APTT but not by tissue thromboplastin.
      Indicating that the low levels of factor VIII and factor V did limit the rate of
      thrombin production. The addition of specific antibodies to factor VIII or factor
      V strongly inhibited thrombin production by aPTT. These data confirm a roughly
      inverse relationship between the concentrations of coagulation proteins and their
      molecular weight in synovial fluid and indicate that thrombin can be generated in
      synovial fluid. The inactivation of thrombin in synovial fluid may be more
      dependent on antithrombin-III than in plasma because of the increased AT
      III/alpha-2 macroglobulin ratio seen in synovial fluid.

PMID- 7573006
TI  - Filterability of mixtures of sickle and normal erythrocytes.
AB  - We investigated the deformability of sickle (SS) cells from 25 patients and
      mixtures of these SS cells with blood type-compatible normal (AA) cells, using a
      nickel mesh filtration system, with the aim of determining optimal goals for
      exchange therapy. We found that for air-equilibrated SS/AA cell mixtures the
      fraction of dense cells (MCHC > 37 g/dl) is the determinant factor in
      filterability and that the dense cells contribute in a linear fashion to the loss
      of filtration up to 15% dense cells (y = -4.41x + 98.23, r = 0.945, P < 0.0001).
      The slope of this effect is approximately 25 times steeper than that of the
      relationship between filtration and percent nondense (MCHC < 37/g/dl) SS cells (y
      = -0.17x + 106.53, r = 0.772, P < 0.0001). A comparison of the proportion of high
      fluorescence reticulocytes to total reticulocytes (HFR ratio), indicating an
      elevation of immature reticulocytes, between six nontransfused patients and six
      exchange-transfused patients showed significant higher values in the
      nontransfused individuals (0.154 +/- 0.051 versus 0.070 +/- 0.054, P < 0.003).
      These results may have implications regarding targets for exchange transfusion
      therapy. Further studies of the effect on transfusion, both simple and exchange,
      on the numbers of dense cells and the proportions and populations of
      reticulocytes and the rheological characteristics of the erythrocyte
      subpopulations seems warranted.

PMID- 7573007
TI  - Serum concentrations of IL-5, GM-CSF, and IL-3 and the production by lymphocytes
      in various eosinophilia.
AB  - The concentrations of interleukin-5 (IL-5), granulocyte-macrophage colony
      stimulating factor GM-CSF, and interleukin-3 (IL-3) in serum and in IL-2
      stimulated lymphocyte culture medium (L-IL2-CM) prepared from patients with
      reactive eosinophilia were measured by enzyme-linked immunosorbent assay (ELISA).
      Serum IL-5 levels were increased in 16 out of 42 cases. GM-CSF and IL-3 were
      below the detectable levels in all sera examined. The concentrations of IL-5 and
      GM-CSF in L-IL2-CM were increased in 10 out of 29 patients. IL-3 was below the
      detectable levels in all L-IL2-CM.

PMID- 7573008
TI  - Interventions in clinical acute renal failure: what are the data?
AB  - A variety of therapeutic approaches have been used both to prevent acute ischemic
      and nephrotoxic renal injury and to improve renal function and reduce mortality
      once acute renal failure (ARF) has developed. Unfortunately, there have been few
      rigorous assessments of the efficacy of these treatment interventions. The
      reasons for the lack of abundant critical data regarding treatment effects in ARF
      are several. First, ARF is a functional disorder. It has a spectrum of
      etiologies, occurs in a variety of clinical settings and varies in severity.
      Second, selected endpoints of treatment success vary and co-morbid factors
      frequently determine outcome. Third, it had been difficult to carry out
      prospective controlled studies in a disorder in which the mortality rate
      approaches 50%. In this review, an effort was made to analyze the available
      literature with a primary focus on controlled studies to determine significant
      prophylactic and treatment effects of various interventions in ARF. Three
      endpoints of therapy (change in renal function, change in course of azotemia, and
      change in mortality) were examined for pharmacologic agents. Changes in course of
      azotemia and mortality were assessed in evaluating different dialysis modes.
      Effect on nitrogen balance, change in course of azotemia, and change in mortality
      were used as endpoints to determine treatment effects of different nutritional
      regimens. When weight was given to prospective controlled studies, some insights
      emerged as to treatment interventions that are most likely to have beneficial
      effects in specific settings of ARF. Among pharmacologic agents, mannitol appears
      to have a positive prophylactic effect in kidney transplantation. There are no
      other significant beneficial effects of diuretics for prophylaxis or as treatment
      in early or established ARF. Of vasoactive agents, there is a relatively small
      amount of data suggesting that diltiazem may have a positive prophylactic effect
      in kidney transplantation, and dopamine possibly is beneficial early in the
      evolutionary phase of ARF. Atrial natriuretic peptide and calcium channel
      blockers may have beneficial effects in established disease. No other
      pharmacologic interventions are supported by substantial data. At best, the
      results are equivocal regarding the use of early and vigorous dialysis in ARF.
      However, there are recent impressive data indicating that the use of
      biocompatible membranes is efficacious in recovery and survival. There is no
      clear evidence that one form of nutritional therapy has advantages over others,
      but some level of amino acid supplementation in addition to basic energy
      replacement is supported by the overall data.

PMID- 7573009
TI  - Racial differences in the prevalence of microalbuminuria in hypertension.
AB  - One hundred nine patients with essential hypertension and without either diabetes
      mellitus or clinical proteinuria were examined to investigate possible racial
      differences in urinary albumin excretion rates. The black hypertensive patients
      were found to have significantly higher urinary albumin excretion rates compared
      with the white patients; in addition, a significantly greater proportion of the
      black patients than the white patients (32% v 14%) had microalbuminuria, defined
      as a urinary albumin excretion rate greater than 30 micrograms/min. These
      differences could not be explained by age, blood pressure, body mass index,
      glycosylated hemoglobin, serum creatinine, duration of hypertension, or type of
      hypertension treatment. Hypertensive renal failure occurs six to 18 times more
      frequently in blacks than in whites; to our knowledge, these data are the first
      to indicate that microalbuminuria may be more prevalent during the course of
      hypertension in black patients and thus may be an early marker for end-organ
      damage susceptibility among hypertensive patients.

PMID- 7573010
TI  - Outcomes of percutaneous kidney biopsy, including those of solitary native
      kidneys.
AB  - A solitary native kidney is generally considered to be an absolute
      contraindication to percutaneous biopsy. However, technical advances, such as
      real-time ultrasound guidance and automated core biopsy systems, provide an
      excellent safety profile with an extremely low risk of catastrophic complications
      and have caused some investigators to call for a reassessment of this
      contraindication. The overall results at our institution are reported. Of 544
      consecutive native and allograft kidney biopsies conducted over 2.5 years, 482
      were performed with an automated core biopsy system and 281 also used real-time
      ultrasound guidance. The overall complication rate was 5.3%. Transient gross
      hematuria was seen in 4.4% and hematoma was seen in 1.5%; no patient experienced
      loss of kidney function and there were no deaths. We recently have begun to
      perform percutaneous biopsy of solitary native kidneys in carefully selected
      patients. To date, nine such procedures have been attempted, with success in
      eight cases. One patient had transient gross hematuria; no other complications
      were noted. This encouraging preliminary experience suggests that otherwise
      uncomplicated adult patients with a solitary kidney might be considered for
      percutaneous biopsy. It now seems appropriate to prospectively evaluate
      percutaneous biopsy of solitary kidneys in a larger cohort of unselected
      patients.

PMID- 7573011
TI  - Compulsive water drinking in the setting of anticholinergic drug use: an
      unrecognized cause of chronic renal failure.
AB  - Compulsive water drinking (psychogenic polydipsia) is a well-recognized clinical
      entity that is often seen in individuals with psychiatric disorders, especially
      schizophrenia. Although urinary tract abnormalities including enlarged bladders
      and hydronephrosis have been reported, the presence of chronic renal failure is
      rarely reported in this disorder. We report four patients with psychogenic
      polydipsia who presented with chronic renal failure due to obstructive uropathy
      in the absence of demonstrable anatomic causes of obstruction. The likely
      mechanism of functional obstructive uropathy is bladder failure due to a
      combination of excessive water ingestion, enlarged bladder volumes, and use of
      anticholinergic medications.

PMID- 7573014
TI  - Superficial repositioning of the artery for chronic hemodialysis: indications and
      prognosis.
AB  - Superficial repositioning of the artery (SRA) is a modality of the blood access
      operation for chronic hemodialysis that has been previously used in cases of
      cardiac failure. We performed 42 SRAs from 1986 to 1993; thereafter, we
      retrospectively investigated the operative indications, postoperative
      complications, and long-term results. Superficial repositioning of the artery was
      indicated for the lack of an appropriate vein (17 cases; 40%), frequent and early
      access failure due to arteriovenous fistula or polytetrafluoroethylene grafts
      (six cases; 14%), venous hypertension (five cases; 12%), and cardiac failure (two
      cases; 5%). The patency rates of the SRAs were 87% at 3 years and 58% at 4.5
      years. There was some difficulty in finding the returning veins in five of 28
      functioning SRAs (18%). The SRA is thus considered to be a secondary-selected
      blood access operation; however, it also may be used as an efficient blood access
      for an extended period of time without any serious complications.

PMID- 7573013
TI  - Changes in antibodies to C1q predict renal relapses in systemic lupus
      erythematosus.
AB  - The presence of elevated plasma levels of autoantibodies against C1q, a
      subcomponent of the first component of complement in sera of patients with
      systemic lupus erythematosus (SLE) has been found to be associated with renal
      involvement. The purpose of this study was to determine whether increases in anti
      C1q antibodies (anti-C1q) precede renal involvement in SLE. Forty-three SLE
      patients were studied longitudinally to determine the relationship between
      manifestations of the disease and levels of anti-C1q as well as to identify
      antibodies against double-stranded DNA (anti-dsDNA). Increased levels of anti-C1q
      were detected in all 14 of the patients who developed proliferative lupus
      nephritis out of 17 patients with renal relapses, which was significantly more
      frequent (P < 0.005) than in patients with nonrenal relapses (six of 16 patients)
      or with inactive disease (two of 10 patients). Increased anti-dsDNA levels were
      observed in 14 of 17 patients with renal relapses compared with 15 of 16 patients
      with nonrenal relapses and five of 10 patients with inactive disease. Significant
      increases in anti-C1q levels prior to the relapse occurred in 10 of 14 patients
      who developed proliferative nephritis and in three of 16 patients with nonrenal
      relapses. Significant increases in anti-dsDNA levels occurred in 11 patients of
      the former group and in nine patients of the latter group. No significant
      increases in anti-C1q or anti-dsDNA levels were observed in the patients with
      inactive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573015
TI  - Effect of albuterol treatment on subsequent dialytic potassium removal.
AB  - End-stage renal disease patients presenting with severe hyperkalemia are
      frequently treated with albuterol to lower their plasma potassium acutely, until
      emergent hemodialysis can be initiated. Such treatment stimulates potassium
      shifts from the extracellular to the intracellular fluid compartments. The
      resulting reduction of potassium concentration gradient between the blood and
      dialysate may potentially attenuate the efficacy of potassium removal during the
      ensuing hemodialysis treatment. To evaluate the effect of prior albuterol
      treatment on dialytic potassium removal, seven chronic hemodialysis patients were
      studied prospectively on two separate occasions. In one study the patients
      received 20 mg nebulized albuterol 30 minutes before dialysis; in the control
      study, albuterol treatment was omitted. Plasma potassium decreased 30 minutes
      after albuterol treatment (-0.84 +/- 0.06 mmol/L; P < 0.001) and remained
      unchanged in the corresponding period of the control experiment. Plasma potassium
      decreased during dialysis in both experimental protocols, but was significantly
      lower throughout dialysis in the albuterol study, as compared with the control
      study. Cumulative dialytic potassium removal was significantly lower following
      albuterol pretreatment compared with the control experiment (29.0 +/- 5.7 mmol v
      49.6 +/- 7.0 mmol; P < 0.001). These observations suggest that acute albuterol
      therapy in patients with end-stage renal disease may substantially decrease
      potassium removal in the ensuing hemodialysis session. This may lead to rebound
      hyperkalemia several hours after the dialysis treatment.

PMID- 7573012
TI  - Urinary secretory immunoglobulin A and free secretory component in
      pyelonephritis.
AB  - The immune defense mechanisms of mucosal surfaces involve secretory
      immunoglobulin A (sIgA) antibodies and, to a lesser degree, other specific and
      nonspecific immune factors. These antibodies are dependent on a secretory
      component (SC) for their transmission through the epithelium. This SC is also
      secreted without Ig as free SC (FSC). The kidney does produce these proteins;
      however, the ability of the lower urinary tract to secrete them has not been
      shown. Thus, an upper urinary tract infection should produce more urinary sIg and
      possibly more FSC than a lower tract infection. To demonstrate this, urine was
      obtained from normal controls (N = 33), cystitis patients (N = 22), and
      pyelonephritis patients (N = 27). Monoclonal antibodies binding to specific
      conformational epitopes were used in an enzyme-linked immunosorbent assay to
      detect the levels of sIgA and FSC in these groups. Previous sIgA measurements
      have been hampered by lack of specificity of the capture antibody. Urine
      creatinine was obtained to correct for the effect of diuresis. A one-tailed
      Student's t-test for nonparametric populations was performed to assess
      differences. The sIgA levels in the normal and cystitis groups were equivalent
      (1.4 micrograms/mg/mL and 1.3 micrograms/mg/mL, respectively; P = 0.32). When
      these two groups were compared with the pyelonephritis group (24.1
      micrograms/mg/mL), a statistically significant difference was seen (P = 0.012 and
      P = 0.011, respectively), with no overlap. There was a statistical difference in
      the levels of FSC in these same groups, but a large degree of overlap.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573016
TI  - The effects of hemodialysis on platelet deposition in prosthetic graft fistulas.
AB  - The effects of hemodialysis on the coagulation system are not completely
      understood. The purpose of these studies was to determine the effects of
      hemodialysis on platelet deposition in prosthetic graft fistulas. Nine patients
      with polytetrafluoroethylene graft fistulas and two with native vein fistulas
      were studied. Dialysis was performed thrice weekly with blood flow rates of 400
      to 450 mL/min and regenerated cellulose hollow-fiber dialyzers. Platelets were
      labeled with oxine-111indium. Images of the fistula were obtained immediately
      after injection (baseline study), postdialysis the same day, the following
      morning, and before and after the next two routine treatments. Images were
      analyzed by drawing regions of interest, and activities were expressed as counts
      per pixel and percent baseline after correction for background and biologic
      clearance and physical decay. There was a marked dialysis-associated enhancement
      of platelet deposition in sites along the graft. More than a twofold increase in
      uptake was noted most frequently in the arterial anastomosis, arterial loop,
      midloop, venous loop, and venous anastomosis regions. The arterial loop and
      midloop regions were most consistently affected. The arterial side of the loop
      during the first dialysis treatment showed an increase from 15 +/- 3 counts/pixel
      (+/- SE) predialysis to 46 +/- 14 counts/pixel postdialysis (P = 0.03, Mann
      Whitney). The uptake increased with dialysis in the midloop region from 12 +/- 2
      counts/pixel to 40 +/- 11 counts/pixel (P = 0.04, paired t-test). The uptake was
      nearly reversed by the next dialysis treatment. Subsequent treatments had a
      similar pattern. No significant change in activity was found in the two patients
      with native vein fistulas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573018
TI  - Peritonitis rate: traditional versus low calcium dialysate.
AB  - The results of nonrandomized retrospective studies have suggested that low
      calcium dialysate (LCD; ionized calcium concentration 1.25 mmol/L) is associated
      with a higher peritonitis rate than traditional dialysate (TD; ionized calcium
      concentration 1.75 mmol/L). For this reason, 86 consecutive new continuous
      ambulatory peritoneal dialysis patients were randomized, in a single-blind
      fashion, to TD or LCD for 1 year. The results were analyzed on an intention-to
      treat basis, no matter what fluid or what modality of treatment was being used at
      the end of the year. The two groups were well matched at baseline. At 1 year, 28
      of 43 TD patients were still on continuous ambulatory peritoneal dialysis (one
      had a catheter changed due to peritonitis), four had a working transplant, one
      had recovered renal function, nine had died, and one had been transferred to
      hemodialysis because of peritonitis. Twenty-seven of 43 LCD patients were on
      continuous ambulatory peritoneal dialysis (one catheter change), nine had a
      working transplant, six had died, and one was on hemodialysis. There were 17
      proven (33 possible) peritonitis episodes in 417 patient-months in the TD group.
      In the LCD group, there were 17 (35 possible) episodes in 432 patient-months. The
      proven peritonitis rate was 0.49 episodes/patient/yr in the TD group versus 0.48
      episodes/patient/yr in the LCD group (P = NS). In conclusion, there is no
      controlled evidence that LCD is associated with a higher incidence of peritonitis
      than TD.

PMID- 7573017
TI  - Predictive value of serum parathyroid hormone levels for bone turnover in
      patients on chronic maintenance dialysis.
AB  - With the increasing occurrence of adynamic bone disease, it is essential to
      determine the level of bone turnover in chronically dialyzed patients before
      instituting vitamin D therapy. To assess the value of serum parathyroid hormone
      (PTH) levels for prediction of bone turnover, we determined sensitivity,
      specificity, and predictive value positive of serum PTH, alone or in combination
      with other variables, in 79 patients who underwent one or two bone biopsies.
      Serum PTH levels were determined by a radioimmunometric assay and were obtained
      at the time of bone biopsies. Patients were classified into (1) low or normal and
      (2) high bone turnover according to the value of activation frequency of bone.
      There were 57 biopsy specimens taken from hemodialysis patients and 39 specimens
      from continuous ambulatory peritoneal dialysis patients (CAPD). All patients with
      serum PTH levels within or below the normal range had low or normal bone
      turnover. Values of serum PTH above 450 pg/mL were 100% and 95.5% specific for
      high bone turnover in hemodialysis and CAPD patients, respectively. Values of
      serum PTH between 65 and 450 pg/mL had worse predictive value positive in CAPD
      patients (48.6% to 78.6%) than in hemodialysis patients (67.3% to 87.1%). When
      other characteristics of the patients were taken into consideration, only age in
      hemodialysis patients and serum ionized calcium in CAPD patients improved the
      predictive value of serum PTH. All hemodialysis patients younger than 45 years of
      age with serum PTH levels above 65 pg/mL (n = 15) had high bone turnover, and
      CAPD patients with low or normal bone turnover had higher serum ionized calcium.
      However, overall, bone turnover could not be predicted by serum PTH measurements
      in 30% of hemodialysis and 51.3% of CAPD patients. The data suggest that for
      patients with serum PTH levels between 65 and 450 pg/mL, bone biopsies are
      indicated to precisely assess bone turnover prior to initiation of vitamin D
      therapy.

PMID- 7573019
TI  - Role of the eosinophil in chronic vascular rejection of renal allografts.
AB  - Obiliterative arteriopathy in chronic renal allograft rejection is caused by
      intimal smooth muscle proliferation accompanied by infiltration of lymphocytes,
      monocytes, and eosinophils. We investigated the role of the eosinophil in chronic
      rejection. Twenty-four allograft nephrectomies were examined for the presence of
      eosinophils on hematoxylin-eosin-stained sections and using epifluorescence on
      Fisher-Giemsa-stained sections. Among 15 cases with chronic rejection,
      eosinophils were detected in 14 cases (93%) with epifluorescence compared with
      only six cases (40%) with hematoxylin-eosin staining (P = 0.005). With
      epifluorescence, eosinophils were identified in the intimal, adventitial, and
      tubulointerstitial compartments in 73%, 80%, and 87% of cases, respectively. To
      examine the pathogenic relevance of the eosinophils in the vessel wall, we
      investigated the effect of eosinophil-conditioned medium on DNA synthesis in
      cultured vascular smooth muscle cells. Autofluorescent eosinophils were isolated
      from atopic human donors using a fluorescence-activated cell sorter. Supernatant
      was collected from eosinophils (1 x 10(6)/mL) cultured overnight in medium with
      0.5% fetal bovine serum. Incorporation of 3H-thymidine into DNA was measured in
      rat and human vascular smooth muscle cells treated for 24 hours with eosinophil
      conditioned medium at 1:20, 1:10, 1:5, and 1:2 dilutions. Eosinophil-conditioned
      medium had a significant dose-dependent stimulatory effect on DNA synthesis in
      both cell lines. Our results indicate that eosinophil involvement in chronic
      renal allograft rejection is more common than previously recognized. The
      stimulatory effect of eosinophil-conditioned medium on vascular smooth muscle
      cell DNA synthesis suggests that eosinophils may be involved in the pathogenesis
      of the obliterative arteriopathy characteristically seen in chronic vascular
      rejection of renal allografts.

PMID- 7573020
TI  - The incidence of renal failure in one hundred consecutive heart-lung transplant
      recipients.
AB  - Between March 1981 and November 1992, 100 heart-lung transplantations were
      performed at our institution. We report on the renal function in the 67 patients
      who survived a minimum of 6 months posttransplantation, and who were aged more
      than 10 years at the time of transplant. Renal function was determined by serial
      measurement of serum creatinine. Mean serum creatinine increased from 0.96 +/-
      0.03 mg/dL at baseline to 1.55 +/- 0.07 mg/dL at 6 months posttransplantation, to
      1.88 +/- 0.11 mg/dL at the end of follow-up (mean follow-up, 50.0 months; range,
      6 to 140 months). The decline in renal function was biphasic, with a rapid
      decrease in the first 6 months, followed by a much slower decline. Three patients
      developed end-stage renal failure. This compares with 14 of 416 cardiac
      transplant recipients at Stanford who developed end-stage renal failure over the
      same period. We conclude that in our large series at a single center the
      incidence of renal impairment and end-stage renal failure is low and similar
      between heart-lung and heart transplant patients.

PMID- 7573021
TI  - Complete recovery from renal infarcts in a patient with mixed connective tissue
      disease.
AB  - We report the case of a 66-year-old woman with mixed connective tissue disease
      (MCD) who had recurrent renal infarcts and renal insufficiency with only mildly
      increased serum anticardiolipin antibodies. After low-dose aspirin therapy, the
      renal lesions resolved, and renal function returned to normal within 3 weeks.

PMID- 7573022
TI  - Heat-insoluble cryoglobulin in a patient with essential type I cryoglobulinemia
      and massive cryoglobulin-occlusive glomerulonephritis.
AB  - We report a case of type I essential cryoglobulinemia with massive cryoglobulin
      occlusive glomerulonephritis, in which the clinical course and the physical
      characteristics of the cryoglobulin were unusual. Nine years before appearance of
      cryoglobulin, this 54-year-old man noted edema and purpura of the lower
      extremities. Renal biopsy performed 2 years later showed large amounts of
      amorphous, weakly eosinophilic, weakly periodic acid-Schiff (PAS)-positive
      materials occluding the glomerular capillaries. Immunostaining showed the
      material to be weakly immunoglobulin (Ig) G positive, and electron microscopy
      showed homogeneous, electron-dense deposits. Nephrotic syndrome and azotemia did
      not respond to steroid treatment, and dialysis was begun 5 years after the
      biopsy. A small amount of cryoglobulin was first detected 2 years later, 9 years
      after the onset of disease. The cryoglobulin had a white gelatinous appearance,
      was resistant to resuspension, and did not redissolve when rewarmed to 37 degrees
      C. Immunoelectrophoresis of the cryoglobulin, which partially dissolved at 54
      degrees C, showed it to be composed of monoclonal IgG-kappa and a small amount of
      albumin. We consider that the unusual physical characteristics of the
      cryoglobulin in this case precipitated a massive cryoglobulin-occlusive
      glomerulonephritis, which progressed to end-stage renal failure in the absence of
      significant cryoglobulinemia during the initial onset of disease.

PMID- 7573023
TI  - Recovery of gastrointestinal function after renal transplantation in a patient
      with sclerosing peritonitis secondary to continuous ambulatory peritoneal
      dialysis.
AB  - We describe the rapid and dramatic improvement in gastrointestinal function that
      occurred after successful renal transplantation in a women with severe sclerosing
      peritonitis secondary to continuous ambulatory peritoneal dialysis (CAPD). We
      postulate that the antiinflammatory effect of the immunosuppressive agents was
      the most important factor leading to the patient's recovery.

PMID- 7573024
TI  - Glomerulonephritis in renal allografts associated with hepatitis C infection: a
      possible relationship with transplant glomerulopathy in two cases.
AB  - Chronic infection with hepatitis C virus (HCV) has been identified as a cause of
      type I membranoproliferative glomerulonephritis (MPGN). HCV infection is common
      in patients with end-stage renal disease and may persist in renal allograft
      recipients. MPGN in the allograft may therefore be a manifestation of persistent
      HCV infection. We report two cases of glomerulopathy with features of both MPGN
      and transplant glomerulopathy in renal transplant patients chronically infected
      with HCV. We discuss the course of interferon alfa therapy in both patients as
      well as a possible relationship of HCV infection with transplant glomerulopathy.

PMID- 7573025
TI  - Idiopathic dialysis ascites in the nineties: resolution after renal
      transplantation.
AB  - The incidence of idiopathic dialysis ascites seems to have decreased since the
      introduction of more effective techniques for control of fluid overload and
      uremia in chronic hemodialysis patients. Most of the patients reported so far had
      some predisposing factor, such as malnutrition or sustained fluid overload. We
      report a case of idiopathic dialysis ascites in a young well-nourished woman with
      an excellent control of fluid overload and in whom biocompatible dialyzer
      membranes and volumetric controlled ultrafiltration had been used since her onset
      of chronic dialysis. Extensive studies excluded the existence of an underlying
      cause for ascites. Ascitic fluid had the characteristics of an exudate, and a
      peritoneal biopsy specimen showed chronic nonspecific inflammatory changes.
      Massive ascites persisted for 6 months, requiring repeated paracentesis, until
      the performance of a successful renal transplantation. Coinciding with the
      recovery of renal function, a dramatic disappearance of ascites was observed.

PMID- 7573026
TI  - BK virus infection in a kidney allograft diagnosed by needle biopsy.

PMID- 7573027
TI  - Severe hypercalcemia in a woman with renal failure.

PMID- 7573029
TI  - Hepatitis C virus in renal transplant patients.

PMID- 7573028
TI  - Transformations between epithelium and mesenchyme: normal, pathological, and
      experimentally induced.
AB  - In this review, we define the two major tissue types, epithelium and mesenchyme,
      and we describe the transformations (transdifferentiations) of epithelium to
      mesenchyme (EMT) and mesenchyme to epithelium (MET) that occur during embryonic
      development. The differentiation of the metanephric blastema provides a striking
      example of MET. Differentiation of metanephric epithelium is promoted by matrix
      molecules and receptors (nidogen, laminins, alpha 6 integrins), hepatic growth
      factor/scatter factor, and products of the genes wnt-1, wnt-4, and Pax-2.
      Transformation of MDCK epithelium to mesenchyme-like cells is promoted in vitro
      by antibodies to E-cadherin, products of v-src, v-ras, and v-mos, and by
      manipulation of the epithelium on collagen gels. Suspension in collagen gel,
      transforming growth factors, and c-fos have also been shown to promote EMT in
      epithelia. We present studies from our laboratory showing that alpha 5 beta 1
      integrin has a role in the EMT of lens epithelium that is brought about by
      suspension in collagen gel. Our laboratory has also shown that transfection with
      the E-cadherin gene induces embryonic corneal fibroblasts to undergo MET and that
      this MET is enhanced by interaction of the differentiating epithelium with living
      fibroblasts. This review calls attention to the roles that EMT and MET might have
      in kidney pathologies and urges further study of the involvement of these
      phenomena in renal development, renal injury, and renal malignancy.

PMID- 7573030
TI  - Excerpts from United States Renal Data System 1995 Annual Data Report.

PMID- 7573031
TI  - Pigmentation, pleiotropy, and genetic pathways in humans and mice.

PMID- 7573032
TI  - Mutations in fibroblast growth factor receptors: phenotypic consequences during
      eukaryotic development.

PMID- 7573033
TI  - A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to
      chromosome 10q2.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that affects
      pigment production and platelet function and causes the deposition of a ceroid
      like material in various tissues. Variability in the phenotype and the presence
      of several potential mouse models suggest that HPS may be a heterogeneous
      disorder. In order to identify a gene responsible for HPS, we collected blood
      samples from a relatively homogeneous population in Puerto Rico where the HPS
      carrier frequency is estimated to be 1 in 21. Analysis of pooled DNA samples
      allowed us to rapidly screen the genome for candidate loci, and significant
      evidence for linkage was detected for a marker on chromosome 10q. This region of
      the human genome is conserved syntenically with the region on mouse chromosome 19
      where two possible mouse models for HPS, pale ear and ruby eye, are located. This
      linkage result was verified with additional markers, and a maximum LOD score of
      5.07 at theta = .001 was calculated for marker D10S198. Haplotype analysis places
      the HPS gene in a region of approximately 14 cM that contains the markers D10S198
      and D10S1239.

PMID- 7573034
TI  - Genetic basis of glycogen storage disease type 1a: prevalent mutations at the
      glucose-6-phosphatase locus.
AB  - Diagnosis of glycogen storage disease (GSD) type 1a currently is established by
      demonstrating the lack of glucose-6-phosphatase (G6Pase) activity in the
      patient's biopsied liver specimen. Recent cloning of the G6Pase gene and
      identification of mutations within the gene that causes GSD type 1a allow for the
      development of a DNA-based diagnostic method. Using SSCP analysis and DNA
      sequencing, we characterized the G6Pase gene of 70 unrelated patients with
      enzymatically confirmed diagnosis of GSD type 1a and detected mutations in all
      except 17 alleles (88%). Sixteen mutations were uncovered that were shown by
      expression to abolish or greatly reduce G6Pase activity and that therefore are
      responsible for the GSD type 1a disorder. R83C and Q347X are the most prevalent
      mutations found in Caucasians, 130X and R83C are most prevalent in Hispanics, and
      R83H is most prevalent in Chinese. The Q347X mutation has thus far been
      identified only in Caucasian patients, and the 130X mutation has been identified
      only in Hispanic patients. Our results demonstrate that the DNA-based analysis
      can accurately, rapidly, and noninvasively detect the majority of mutations in
      GSD type 1a. This DNA-based diagnosis now permits prenatal diagnosis among at
      risk patients and serves as a database in screening and counseling patients
      clinically suspected of having this disease.

PMID- 7573037
TI  - Molecular characterization of minor gene rearrangements in Finnish patients with
      heterozygous familial hypercholesterolemia: identification of two common missense
      mutations (Gly823-->Asp and Leu380-->His) and eight rare mutations of the LDL
      receptor gene.
AB  - Two deletions of the low-density lipoprotein (LDL) receptor gene were previously
      shown to account for about two thirds of all mutations causing familial
      hypercholesterolemia (FH) in Finland. We screened the DNA samples from a cohort
      representing the remaining 30% of Finnish heterozygous FH patients by amplifying
      all the 18 exons of the receptor gene by PCR and searching for DNA variations
      with the SSCP technique. Ten novel mutations were identified, comprising two
      nonsense and seven missense mutations as well as one frameshift mutation caused
      by a 13-bp deletion. A single nucleotide change, substituting adenine for
      guanidine at position 2533 and resulting in an amino acid change of glycine to
      aspartic acid at codon 823, was found in DNA samples from 14 unrelated FH
      probands. This mutation (FH-Turku) affects the sequence encoding the putative
      basolateral sorting signal of the LDL receptor protein; however, the exact
      functional consequences of this mutation are yet to be examined. The FH-Turku
      gene and another point mutation (Leu380-->His or FH-Pori) together account for
      approximately 8% of the FH-causing genes in Finland and are particularly common
      among FH patients from the southwestern part of the country (combined, 30%).
      Primer-introduced restriction analysis was applied for convenient assay of the FH
      Turku and FH-Pori point mutations. In conclusion, this paper demonstrates the
      unique genetic background of FH in Finland and describes a commonly occurring FH
      gene with a missense mutation closest to the C terminus thus far reported.

PMID- 7573036
TI  - Molecular genetics of cystinuria: identification of four new mutations and seven
      polymorphisms, and evidence for genetic heterogeneity.
AB  - A cystinuria disease gene (rBAT) has been recently identified, and some mutations
      causing the disease have been described. The frequency of these mutations has
      been investigated in a large sample of 51 Italian and Spanish cystinuric
      patients. In addition, to identify new mutated alleles, genomic DNA has been
      analyzed by an accurate and sensitive method able to detect nucleotide changes.
      Because of the lack of information available on the genomic structure of rBAT
      gene, the study was carried out using the sequence data so far obtained by us.
      More than 70% of the entire coding sequence and 8 intron-exon boundaries have
      been analyzed. Four new mutations and seven intragenic polymorphisms have been
      detected. All mutations so far identified in rBAT belong only to cystinuria type
      I alleles, accounting for approximately 44% of all type I cystinuric chromosomes.
      Mutation M467T is the most common mutated allele in the Italian and Spanish
      populations. After analysis of 70% of the rBAT coding region, we have detected
      normal sequences in cystinuria type II and type III chromosomes. The presence of
      rBAT mutated alleles only in type I chromosomes of homozygous (type I/I) and
      heterozygous (type I/III) patients provides evidence for genetic heterogeneity
      where rBAT would be responsible only for type I cystinuria and suggests a
      complementation mechanism to explain the intermediate type I/type III phenotype.

PMID- 7573039
TI  - Deletions of the survival motor neuron gene in unaffected siblings of patients
      with spinal muscular atrophy.
AB  - DNA studies in 103 spinal muscular atrophy (SMA) patients from The Netherlands
      revealed homozygosity for a survival motor neuron (SMN) deletion in 96 (93%) of
      103. Neuronal apoptosis inhibitory protein deletions were found in 38 (37%) of
      103 and occurred most frequently in SMA type I. SMN deletions have not yet been
      described to occur in healthy subjects. In this study, however, four unaffected
      sibs from two SMA families showed homozygosity for SMN deletions. Homozygosity
      for an SMN deletion in unaffected persons seems to be very rare. Therefore,
      demonstration of a homozygous SMN deletion in a clinically presumed SMA patient
      should be considered as a confirmation of the diagnosis, whether or not SMN is in
      fact the causal gene for SMA.

PMID- 7573035
TI  - An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting
      mitochondrial import of the precursor protein.
AB  - A mutation in the mitochondrial targeting sequence was characterized in a male
      patient with X chromosome-linked pyruvate dehydrogenase E1 alpha deficiency. The
      mutation was a base substitution of G by C at nucleotide 134 in the mitochondrial
      targeting sequence of the PDHA1 gene, resulting in an arginine-to-proline
      substitution at codon 10 (R10P). Pyruvate dehydrogenase activity in cultured skin
      fibroblasts was 28% of the control value, and immunoblot analysis revealed a
      decreased level of pyruvate dehydrogenase E1 alpha immunoreactivity. Chimeric
      constructs in which the normal and mutant pyruvate dehydrogenase E1 alpha
      targeting sequences were attached to the mitochondrial matrix protein ornithine
      transcarbamylase were synthesized in a cell free translation system, and
      mitochondrial import of normal and mutant proteins was compared in vitro. The
      results show that ornithine transcarbamylase targeted by the mutant pyruvate
      dehydrogenase E1 alpha sequence was translocated into the mitochondrial matrix at
      a reduced rate, suggesting that defective import is responsible for the reduced
      pyruvate dehydrogenase level in mitochondria. The mutation was also present in an
      affected brother and the mildly affected mother. The clinical presentations of
      this X chromosome-linked disorder in affected family members are discussed. To
      our knowledge, this is the first report of an amino acid substitution in a
      mitochondrial targeting sequence resulting in a human genetic disease.

PMID- 7573038
TI  - A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene.
AB  - We present evidence that a 480G-->A transition in the coding region of the beta
      glucuronidase gene, which results in an aspartic-acid-to-asparagine substitution
      at amino acid position 152 (D152N), produces a pseudodeficiency allele (GUSBp)
      that leads to greatly reduced levels of beta-glucuronidase activity without
      apparent deleterious consequences. The 480G-->A mutation was found initially in
      the pseudodeficient mother of a child with mucopolysaccharidosis VII (MPSVII),
      but it was not on her disease-causing allele, which carried the L176F mutation.
      The 480G-->A change was also present in an unrelated individual with another
      MPSVII allele who had unusually low beta-glucuronidase activity, but whose
      clinical symptoms were probably unrelated to beta-glucuronidase deficiency. This
      individual also had an R357X mutation, probably on his second allele. We screened
      100 unrelated normal individuals for the 480G-->A mutation with a PCR method and
      detected one carrier. Reduced beta-glucuronidase activity following transfection
      of COS cells with the D152N cDNA supported the causal relationship between the
      D152N allele and pseudodeficiency. The mutation reduced the fraction of expressed
      enzyme that was secreted. Pulse-chase experiments indicated that the reduced
      activity in COS cells was due to accelerated intracellular turnover of the D152N
      enzyme. They also suggested that a potential glycosylation site created by the
      mutation is utilized in approximately 50% of the enzyme expressed.

PMID- 7573040
TI  - Marked phenotypic heterogeneity associated with expansion of a CAG repeat
      sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus.
AB  - The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant
      cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group
      of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type
      I patients from families segregating SCA3 share clinical features in common with
      those with Machado-Joseph disease (MJD), the gene of which maps to the same
      region. We show here that the disease gene segregating in each of three French
      ADCA type I kindreds and in a French family with neuropathological findings
      suggesting the ataxochoreic form of dentatorubropallidoluysian atrophy carries an
      expanded CAG repeat sequence located at the same locus as that for MJD. Analysis
      of the mutation in these families shows a strong negative correlation between
      size of the expanded CAG repeat and age at onset of clinical disease. Instability
      of the expanded triplet repeat was not found to be affected by sex of the parent
      transmitting the mutation. Evidence was found for somatic and gonadal mosaicism
      for alleles carrying expanded trinucleotide repeats.

PMID- 7573041
TI  - The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the
      Golgi complex.
AB  - The oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder affecting
      the lens, kidney, and CNS. The predicted amino acid sequence of the OCRL gene,
      OCRL-1, was used to develop antibodies against the OCRL-1 protein. Western blot
      analysis using affinity-purified serum against the amino terminus of the OCRL-1
      gene product (ocrl-1) demonstrates a single protein of 105 kD in fibroblasts of a
      normal individual that is absent in fibroblasts of an OCRL patient who lacks OCRL
      1 transcript. A single protein with the same electrophoretic mobility is found by
      western analysis in various human cultured cell lines, and approximately the same
      size protein is also found in all mouse tissues tested. Northern analysis of
      various human and mouse tissues demonstrate that OCRL-1 transcript is expressed
      in nearly all tissues examined. By immunofluorescence, the ocrl-1 antibody stains
      a juxtanuclear region in normal fibroblast cells, while no specific staining is
      evident in the OCRL patient who produces no transcript. Colocalization of the
      ocrl-1 protein to the Golgi complex was demonstrated using a known monoclonal
      antibody against a Golgi-specific coat protein, beta-COP (beta coatomer protein).

PMID- 7573042
TI  - Selective intestinal malabsorption of vitamin B12 displays recessive mendelian
      inheritance: assignment of a locus to chromosome 10 by linkage.
AB  - Juvenile megaloblastic anemia caused by selective intestinal malabsorption of
      vitamin B12 has been considered a distinct condition displaying autosomal
      recessive inheritance. It appears to have a worldwide distribution, and
      comparatively high incidences were reported 30 years ago in Finland and Norway.
      More recently, the Mendelian inheritance of the condition has been questioned
      because almost no new cases have occurred in these populations. Here we report
      linkage studies assigning a recessive-gene locus for the disease to chromosome 10
      in previously diagnosed multiplex families from Finland and Norway, proving the
      Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM
      interval between markers D10S548 and D10S466, with a multipoint maximum lod score
      (Zmax) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in
      these families did not appear to constitute any examples of nonpenetrance. We
      hypothesize that the paucity of new cases in these populations is due either to a
      dietary effect on the gene penetrance that has changed with time, or to a drop in
      the birth rate in subpopulations showing enrichment of the mutation, or to both
      of these causes.

PMID- 7573044
TI  - Autosomal dominant zonular cataract with sutural opacities localized to
      chromosome 17q11-12.
AB  - Congenital cataracts constitute a morphologically and genetically heterogeneous
      group of diseases that are a major cause of childhood blindness. Different loci
      for hereditary congenital cataracts have been mapped to chromosomes 1, 2, 16, and
      17q24. We report linkage of a gene causing a unique form of autosomal dominant
      zonular cataracts with Y-sutural opacities to chromosome 17q11-12 in a three
      generation family exhibiting a maximum lod score of 3.9 at D17S805. Multipoint
      analysis gave a 1-lod confidence interval of 17 cM. This interval is bounded by
      the markers D17S799 and D17S798, a region that would encompass a number of
      candidate genes including that coding for beta A3/A1-crystallin.

PMID- 7573045
TI  - Linkage of familial dilated cardiomyopathy to chromosome 9. Heart Muscle Disease
      Study Group.
AB  - Idiopathic dilated cardiomyopathy is a heart muscle disease of unknown etiology,
      characterized by impaired myocardial contractility and ventricular dilatation.
      The disorder is an important cause of morbidity and mortality and represents the
      chief indication for heart transplantation. Familial transmission is often
      recognized (familial dilated cardiomyopathy, or FDC), mostly with autosomal
      dominant inheritance. In order to understand the molecular genetic basis of the
      disease, a large six-generation kindred with autosomal dominant FDC was studied
      for linkage analysis. A genome-wide search was undertaken after a large series of
      candidate genes were excluded and was then extended to two other families with
      autosomal dominant pattern of transmission and identical clinical features.
      Coinheritance of the disease gene was excluded for > 95% of the genome, after 251
      polymorphic markers were analyzed. Linkage was found for chromosome 9q13-q22,
      with a maximum multipoint lod score of 4.2. There was no evidence of
      heterogeneity. The FDC locus was placed in the interval between loci D9S153 and
      D9S152. Several candidate genes for causing dilated cardiomyopathy map in this
      region.

PMID- 7573043
TI  - Genetic mapping of the dentinogenesis imperfecta type II locus.
AB  - Dentinogenesis imperfecta type II (DGI-II) is an autosomal dominant disorder of
      dentin formation, which has previously been mapped to chromosome 4q12-21. In the
      current study, six novel short tandem-repeat polymorphisms (STRPs) have been
      isolated, five of which show significant evidence of linkage to DGI-II. To
      determine the order of the STRPs and define the genetic distance between them,
      nine loci (including polymorphisms for two known genes) were mapped through the
      CEPH reference pedigrees. The resulting genetic map encompasses 16.3 cM on the
      sex-averaged map. To combine this map with a physical map of the region, all of
      the STRPs were mapped through a somatic cell hybrid panel. The most likely
      location for the DGI-II locus within the fixed marker map is in the D4S2691
      D4S2692 interval of 6.6 cM. The presence of a marker that shows no recombination
      with the DGI-II phenotype between the flanking markers provides an important
      anchor point for the creation of physical continuity across the DGI-II candidate
      region.

PMID- 7573048
TI  - Recombination and maternal age-dependent nondisjunction: molecular studies of
      trisomy 16.
AB  - Trisomy 16 is the most common human trisomy, occurring in > or = 1% of all
      clinically recognized pregnancies. It is thought to be completely dependent on
      maternal age and thus provides a useful model for studying the association of
      increasing maternal age and nondisjunction. We have been conducting a study to
      determine the parent and meiotic stage of origin of trisomy 16 and the possible
      association of nondisjunction and aberrant recombination. In the present report,
      we summarize our observations on 62 spontaneous abortions with trisomy 16. All
      trisomies were maternally derived, and in virtually all the error occurred at
      meiosis I. In studies of genetic recombination, we observed a highly significant
      reduction in recombination in the trisomy-generating meioses by comparison with
      normal female meioses. However, most cases of trisomy 16 had at least one
      detectable crossover between the nondisjoined chromosomes, indicating that it is
      reduced--and not absent--recombination that is the important predisposing factor.
      Additionally, our data indicate an altered distribution of crossing-over in
      trisomy 16, as we rarely observed crossovers in the proximal long and short arms.
      Thus, it may be that, at least for trisomy 16, the association between maternal
      age and trisomy is due to diminished recombination, particularly in the proximal
      regions of the chromosome.

PMID- 7573049
TI  - The natural history of Down syndrome conceptuses diagnosed prenatally that are
      not electively terminated.
AB  - The pregnancy outcomes on cases of Down syndrome diagnosed prenatally in which
      the mother did not elect termination were evaluated in data reported to a
      comprehensive Register of Down syndrome for England and Wales for 1989-94. In the
      168 cases in which placental biopsy was not used, the overall rate of spontaneous
      loss was 35%, but this figure masks considerable heterogeneity by gestational
      stage at ascertainment. Data on ages at diagnostic procedure and on pregnancy
      termination enabled a more precise survival analysis. The loss rates were
      approximately 50% for those fetuses ascertained at 15-17 completed wk, 43% at 18
      wk, 31% at 19 wk, 25% at 20 wk, and then a leveling off at approximately 20%-25%
      for fetuses ascertained at 21-28 completed wk. For fetuses ascertained prior to
      18 wk, there was no evidence that maternal age was associated with fetal loss,
      consistent with earlier reports. At 18 wk and after, however, maternal age was on
      the average approximately 3 years greater in fetuses that were lost. Comparison
      of successive gestational birth cohorts provided no evidence in these 168 cases
      that the diagnostic procedure itself had any effect on loss or that selective
      ascertainment of mothers in risk of loss had any effect on the results. In
      contrast, in the 21 cases in which placental biopsy had been undertaken, the
      overall loss rates were not only higher when appropriate comparisons could be
      made, but there was some evidence for selective ascertainment and/or procedure
      associated losses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573046
TI  - Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q.
AB  - Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory
      neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie
      Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant
      trait with a variable age at onset of symptoms associated with progressive axonal
      neuropathy. In some families, the locus that predisposes to CMT2 has been
      demonstrated to map to the distal portion of the short arm of chromosome 1. Other
      families with CMT2 do not show linkage with 1p markers, suggesting genetic
      heterogeneity in CMT2. We investigated linkage in a single large kindred with
      autosomal dominant CMT2. The gene responsible for CMT2 in this kindred (CMT2B)
      was mapped to the interval between the microsatellite markers D3S1769 and D3S1744
      in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further
      refine the disease gene region and may ultimately lead to the identification of a
      gene defect that underlies the CMT2 phenotype.

PMID- 7573047
TI  - The 13q- syndrome: the molecular definition of a critical deletion region in band
      13q32.
AB  - Patients with interstitial deletions of the long arm of chromosome 13 may have
      widely varying phenotypes. From cytogenetic analysis, we have postulated that
      there is a discrete region in 13q32 where deletion leads to a syndrome of severe
      malformations, including digital and brain anomalies. To test this hypothesis at
      the molecular level, we have studied the deletions in 17 patients; 5 had severe
      malformations, while the remaining 12 had only minor malformations. Our results
      indicate that the deletions in the severely affected patients all involve an
      overlapping region in q32, while the deletions in the mildly affected patients
      include some, but not all, of this overlapping region. Our findings are
      consistent with the hypothesis that the severely malformed 13q- phenotype results
      from the deletion of a critical region in 13q32. This region is presently defined
      as lying between D13S136 and D13S147 and is on the order of 1 Mb in size.

PMID- 7573050
TI  - Isolated persistent hypermethioninemia.
AB  - New information has been obtained on 30 patients with isolated persistent
      hypermethioninemia, most of them previously unreported. Biopsies to confirm the
      presumptive diagnosis of partially deficient activity of ATP: L-methionine S
      adenosyltransferase (MAT; E.C.2.5.1.6) in liver were not performed on most of
      these patients. However, none showed the clinical findings or the extreme
      elevations of serum folate previously described in other patients with isolated
      hypermethioninemia considered not to have hepatic MAT deficiency. Patients
      ascertained on biochemical grounds had no neurological abnormalities, and 27/30
      had IQs or Bayley development-index scores within normal limits or were judged to
      have normal mental development. Methionine transamination metabolites accumulated
      abnormally only when plasma methionine concentrations exceeded 300-350 microM and
      did so more markedly after 0.9 years of age. Data were obtained on urinary
      organic acids as well as plasma creatinine concentrations. Patterns of
      inheritance of isolated hypermethioninemia were variable. Considerations as to
      the optimal management of this group of patients are discussed.

PMID- 7573052
TI  - Genetic analysis of kifafa, a complex familial seizure disorder.
AB  - Kifafa is the Swahili name for an epileptic seizure disorder, first reported in
      the early 1960s, that is prevalent in the Wapogoro tribe of the Mahenge region of
      Tanzania in eastern Africa. A 1990 epidemiological survey of seizure disorders in
      this region reported a prevalence in the range of 19/1,000-36/1,000, with a mean
      age at onset of 11.6 years; 80% of those affected had onset prior to 20 years of
      age. A team of investigators returned to Tanzania in 1992 and collected data on >
      1,600 relatives of 26 probands in 20 kifafa families. We have undertaken a
      genetic analysis of these data in order to detect the presence of familial
      clustering and whether such aggregation could be attributed to genetic factors.
      Of the 127 affected individuals in these pedigrees, 23 are first-degree relatives
      (parent, full sibling, or offspring) of the 26 probands; 20 are second-degree
      relatives (half-sibling, grandparent, uncle, or aunt). When corrected for age,
      the risk to first-degree relatives is .15; the risk to second-degree relatives is
      .063. These risks are significantly higher than would be expected if there were
      no familial clustering. Segregation analysis, using PAP (rev.4.0), was undertaken
      to clarify the mode of inheritance. Among the Mendelian single-locus models, an
      additive model was favored over either a dominant, recessive, or codominant
      model. The single-locus model could be rejected when compared with the mixed
      Mendelian model (inclusion of a polygenic background), although the major-gene
      component tends to be recessive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573051
TI  - Lysosomal free sialic acid storage disorders with different phenotypic
      presentations--infantile-form sialic acid storage disease and Salla disease-
      represent allelic disorders on 6q14-15.
AB  - Similarities in biochemical findings have suggested that Salla disease (SD) and
      the infantile form of sialic acid storage disease (ISSD) could represent allelic
      disorders, despite their drastically different clinical phenotypes. SD and ISSD
      are both characterized by lysosomal storage of free N-acetyl neuraminic acid.
      However, in SD the increase detected in urine is 8-24-fold, whereas in ISSD the
      corresponding amount is 20-50-fold and patients are also more severely affected.
      Here we report linkage studies in 50 Finnish SD families and 26 non-Finnish
      families with no genealogical connections to Finns affected either with the
      Finnish type of SD, the "intermediate" form of the disease, or ISSD. All forms of
      the disease show linkage to the same locus on 6q14-q15. Haplotype analyses of
      Finnish SD chromosomes revealed one common haplotype, which was also seen in most
      of the non-Finnish patients with Finnish type of SD. This ancestral haplotype
      deviated from those observed in ISSD patients, who had a different common
      haplotype.

PMID- 7573053
TI  - Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent
      diabetes mellitus (IDDM8) on chromosome 6q25-q27.
AB  - Affected-sib-pair analyses were performed using 104 Caucasian families to map
      genes that predispose to insulin-dependent diabetes mellitus (IDDM). We have
      obtained linkage evidence for D6S446 (maximum lod score [MLS] = 2.8) and for
      D6S264 (MLS = 2.0) on 6q25-q27. Together with a previously reported data set,
      linkage can be firmly established (MLS = 3.4 for D6S264), and the disease locus
      has been designated IDDM8. With analysis of independent families, we confirmed
      linkage evidence for the previously identified IDDM3 (15q) and DDM7 (2q). We also
      typed additional markers in the regions containing IDDM3, IDDM4, IDDM5, and
      IDDM8. Preliminary linkage evidence for a novel region on chromosome 4q (D4S1566)
      has been found in 47 Florida families (P < .03). We also found evidence of
      linkage for two regions previously identified as potential linkages in the
      Florida subset: D3S1303 on 3q (P < .04) and D7S486 on 7q (P < .03). We could not
      confirm linkage with eight other regions (D1S191, D1S412, D4S1604, D8S264,
      D8S556, D10S193, D13S158, and D18S64) previously identified as potential
      linkages.

PMID- 7573054
TI  - Two-locus maximum lod score analysis of a multifactorial trait: joint
      consideration of IDDM2 and IDDM4 with IDDM1 in type 1 diabetes.
AB  - To investigate the genetic component of multifactorial diseases such as type 1
      (insulin-dependent) diabetes mellitus (IDDM), models involving the joint action
      of several disease loci are important. These models can give increased power to
      detect an effect and a greater understanding of etiological mechanisms. Here, we
      present an extension of the maximum lod score method of N. Risch, which allows
      the simultaneous detection and modeling of two unlinked disease loci. Genetic
      constraints on the identical-by-descent sharing probabilities, analogous to the
      "triangle" restrictions in the single-locus method, are derived, and the size and
      power of the test statistics are investigated. The method is applied to affected
      sib-pair data, and the joint effects of IDDM1 (HLA) and IDDM2 (the INS VNTR) and
      of IDDM1 and IDDM4 (FGF3-linked) are assessed with relation to the development of
      IDDM. In the presence of genetic heterogeneity, there is seen to be a significant
      advantage in analyzing more than one locus simultaneously. Analysis of these
      families indicates that the effects at IDDM1 and IDDM2 are well described by a
      multiplicative genetic model, while those at IDDM1 and IDDM4 follow a
      heterogeneity model.

PMID- 7573055
TI  - Models of comorbidity for multifactorial disorders.
AB  - We develop several formal models for comorbidity between multifactorial
      disorders. Based on the work of D. N. Klein and L. P. Riso, the models include
      (i) alternate forms, where the two disorders have the same underlying continuum
      of liability; (ii) random multiformity, in which affection status on one disorder
      abruptly increases risk for the second; (iii) extreme multiformity, where only
      extreme cases have an abruptly increased risk for the second disorder; (iv) three
      independent disorders, in which excess comorbid cases are due to a separate,
      third disorder; (v) correlated liabilities, where the risk factors for the two
      disorders correlate; and (vi) direct causal models, where the liability for one
      disorder is a cause of the other disorder. These models are used to make
      quantitative predictions about the relative proportions of pairs of relatives who
      are classified according to whether each relative has neither disorder, disorder
      A but not B, disorder B but not A, or both A and B. For illustration, we analyze
      data on major depression (MD) and generalized anxiety disorder (GAD) assessed in
      adult female MZ and DZ twins, which enable estimation of the relative impact of
      genetic and environmental factors. Several models are rejected--that comorbid
      cases are due to chance; multiformity of GAD; a third independent disorder; and
      GAD being a cause of MD. Of the models that fit the data, correlated liabilities,
      MD causes GAD, and reciprocal causation seem best. MD appears to be a source of
      liability for GAD. Possible extensions to the models are discussed.

PMID- 7573056
TI  - Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations
      in Leber hereditary optic neuropathy: molecular, biochemical, and clinical
      findings.

PMID- 7573057
TI  - Genetic heterogeneity of breast-ovarian cancer revisited. Breast Cancer Linkage
      Consortium.

PMID- 7573058
TI  - CFTR gene variant for patients with congenital absence of vas deferens.

PMID- 7573059
TI  - The ataxia-telangiectasia-variant genes 1 and 2 are distinct from the ataxia
      telangiectasia gene on chromosome 11q23.1.

PMID- 7573060
TI  - Fine localization of the locus for autosomal dominant retinitis pigmentosa on
      chromosome 17p.

PMID- 7573061
TI  - Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large
      inbred Bedouin family from Israel.

PMID- 7573062
TI  - Refinement of the OPA1 gene locus on chromosome 3q28-q29 to a region of 2-8 cM,
      in one Cuban pedigree with autosomal dominant optic atrophy type Kjer.

PMID- 7573063
TI  - Genetic mapping of the human amphiphysin gene (AMPH) at 7p14-p13 excludes its
      involvement in retinitis pigmentosa 9 or dominant cystoid macular dystrophy.

PMID- 7573064
TI  - Localization of the candidate gene D-amino acid oxidase outside the refined I-cM
      region of spinocerebellar ataxia 2.

PMID- 7573065
TI  - Association analysis of the monoamine oxidase A gene in bipolar affective
      disorder by using family-based internal controls.

PMID- 7573066
TI  - Mutations in galactosemia.

PMID- 7573067
TI  - Defining "proband".

PMID- 7573068
TI  - Standardized pedigree nomenclature.

PMID- 7573069
TI  - Establishment size and risk of occupational injury.
AB  - For many years, the annual survey of occupational injuries and illnesses by the
      Federal Bureau of Labor Statistics (BLS) has consistently reported, without
      explanation, that injury rates in the smaller establishments (< 50 employees) are
      substantially lower than those for midsize establishments (100-499 employees).
      Also during those years, a remarkable increase has been reported in the injury
      rate in large companies, following the imposition of stiff fines for failure to
      keep required injury records. The rate patterns are identical for Michigan and
      the country in general. We investigated possible causes for lower injury rates in
      small establishments since such rates are inconsistent with reports of higher
      fatality rates in small establishments in the mining, construction,
      manufacturing, and transportation industries and higher, or at least comparable,
      injury rates for small establishments in the mining industry. They are also
      inconsistent with increased turnover and decreased availability of occupational
      safety services in small companies. Moreover, injury severity, as measured by
      missed worktime, is greater for workers in small establishments. We investigated
      the possibility that interactions of workforce or injury characteristics with
      establishment size could explain the rate differences. We also reviewed the
      available literature to see whether differences in labor turnover rates could
      explain the BLS findings. Graphical and statistical analyses of the 1988 CPS
      Annual Demographic File, a sample of employed persons in the U.S. workforce,
      failed to identify any associations between workforce characteristics and
      enterprise size that would explain the lower rates. Similarly, graphical and
      statistical analyses of all Michigan workers incurring a compensable injury in
      1986 failed to indicate any associations between injury characteristics and
      establishment size that would explain the lower rates. The potential role of
      labor turnover on the injury rate was analyzed from data in the literature on
      turnover rate by establishment size and risk of injury by time on the job. None
      of these analyses explains the lower injury rates reported for small
      establishments. This leaves underreporting of injuries from small establishments
      as a substantial possibility. If small establishments were subject to the same
      injury incidence rates as midsize establishments, then the 1986 survey for
      Michigan may have missed as many as 54,000 injuries (and far more nationally). We
      suggest that BLS undertake methodological studies to validate the completeness of
      reporting from small establishments.

PMID- 7573071
TI  - Finnish Institute of Occupational Health Asbestos Program 1987-1992.
AB  - In 1987-1992, the Finnish Institute of Occupational Health (FIOH) implemented a
      nationwide asbestos program aimed at preventing asbestos-related risks in good
      cooperation with governmental authorities, industry, trade unions, the health
      care and insurance systems, and mass media. The goals were to minimize all
      exposure to asbestos, identify people exposed at work, and improve the
      diagnostics of asbestos diseases, especially cancers. The program entailed
      several concrete actions and extensive dissemination of information, training,
      services, and scientific research. As proposed by the State Asbestos Committee,
      new use of asbestos products was banned and strict regulations were applied to
      renovation and inspection of old buildings. The screening study of asbestos
      induced diseases included 18,943 current and retired workers from house building,
      shipyard, and asbestos industries. Pleural and parenchymal changes were found in
      4,133 persons (22%), who were referred to further clinical examinations as
      suspected cases of an occupational disease. It was estimated that past exposure
      of asbestos among the Finnish population of 5 million causes > 150 mesotheliomas
      and lung cancers annually, totalling > 2,000 asbestos-induced cancer deaths by
      the year 2010. Although several major control actions were made or started during
      the program, the bulk of the preventive work still lies ahead.

PMID- 7573070
TI  - Collection of a single alveolar exhaled breath for volatile organic compounds
      analysis.
AB  - Measurement of specific organic compounds in exhaled breath has been used as an
      indicator of recent exposure to pollutants or as an indicator of the health of an
      individual. A typical application involves the collection of multiple breaths
      onto a sorbent cartridge or into an evacuated canister with the use of a
      relatively complex sampling apparatus. A new method has been developed wherein a
      single exhaled breath is directly transferred from the mouth into an evacuated 1
      l or 1.8 l stainless steel SUMMA canister. The single breath canister (SBC)
      method avoids the necessity for a complex sampling system requiring maintenance
      and cleaning and allows easy collection of samples. Additionally, it is possible
      to collect a rapid sequence of samples from a subject to establish the
      elimination curve subsequent to an exposure to specific volatile organic
      compounds with a theoretical resolution of adjacent breaths. The SBC method was
      compared to an accepted canister based sampling system to assure comparability
      and then used to demonstrate its utility by measuring the absorption and
      elimination of chloroform during and after exposure to chlorinated shower water.

PMID- 7573072
TI  - Biomonitoring of low levels of exposure to styrene.

PMID- 7573073
TI  - Distinguishability of the video display terminal (VDT) as a source of magnetic
      field exposure.
AB  - Magnetic field strength or its surrogate has been used as the measurement of
      exposure in all studies involving field exposure. Video display terminals (VDTs)
      are considered a minor source on this scale because its field strengths lie in
      the low range of magnetic fields. Several experiments show, however, that field
      strength may not be the only relevant variable in determining exposure. This
      paper explores the use of a method based on "effects functions" to determine the
      extent to which the VDT can be distinguished from other sources. It is shown that
      VDT exposure may be of consequence if exposure depends on certain types of time
      variation of the field. Because of the incompleteness of science in this area,
      this is a demonstration of a method rather than an actual demonstration of VDT as
      a significant source of exposure.

PMID- 7573074
TI  - Potential pitfall in using cumulative exposure in exposure-response
      relationships: demonstration and discussion.
AB  - Cumulative exposure is frequently used as a measure of exposure in the
      quantitative analysis of epidemiologic studies. It is recognized that the imposed
      symmetry between duration and intensity of exposure is a potential problem with
      this measure, but it is less widely recognized that the finding of an exposure
      response relationship, using cumulative exposure as the exposure metric, does not
      necessarily imply that exposures were accurately or even consistently estimated.
      This report describes a simulation study drawn from a nested case-control
      analysis of mesothelioma in a cohort of asbestos cement workers. Intensity of
      exposure in the range of 0.1-40 fibers/ml was randomly assigned to subjects.
      Logistic regression analysis demonstrated that there was no association between
      mesothelioma risk and the randomly assigned intensity of exposure. However, in
      171 (86%) of 200 trials, mesothelioma risk was significantly associated with
      cumulative exposure, even though intensity of exposure remained randomly
      assigned. A strong exposure-response relationship might thus be misleading. One
      would be more confident about quantitative risk assessment when there are a large
      number of independent studies available for analysis.

PMID- 7573075
TI  - Assessment of mortality in the construction industry in the United States, 1984
      1986.
AB  - Construction, one of the larger industries in the United States, employs 7.6
      million workers, many in skilled trades occupations. Previously published data
      about potential worksite exposures and mortality of construction site workers are
      limited. We analyzed occupation and industry codes on death certificates from 19
      U.S. states to evaluate mortality risks among men and women usually employed in
      construction occupations. Proportionate mortality ratios (PMRs) for cancer and
      several other chronic diseases were significantly elevated among 61,682 white
      male construction workers who died between 1984 and 1986. Men younger than age
      65, who were probably still employed immediately prior to death, had
      significantly elevated PMRs for cancer, asbestos-related diseases, mental
      disorders, alcohol-related disease, digestive diseases, falls, poisonings,
      traumatic fatalities that are usually work-related, and homicides. Elevated PMRs
      for many of the same causes were observed to a lesser degree for black men and
      white women whose usual industry was construction. In addition, women experienced
      excess cancer of the connective tissue and suicide mortality. Various skilled
      construction trades had elevated PMRs for specific sites, such as bone cancer and
      melanoma in brickmasons, stomach cancer in roofers and brickmasons, kidney and
      bone cancer in concrete/terrazzo finishers, nasal cancer in plumbers, pulmonary
      tuberculosis in laborers, scrotal cancer and aplastic anemia in electricians,
      acute myeloid leukemia in boilermakers, rectal cancer and multiple sclerosis in
      electrical power installers, and lung cancer in structural metal workers. Using a
      standard population of blue collar workers did not result in fewer elevated PMRs
      for construction workers. Despite lifestyle differences and other limitations of
      the study, the large numbers of excess deaths observed in this study indicate the
      need for preventive action for construction workers.

PMID- 7573076
TI  - Childhood cancer and paternal exposure to ionizing radiation: a second report
      from the Oxford Survey of Childhood Cancers.
AB  - Paternal occupational data already collected as part of the Oxford Survey of
      Childhood Cancers have been reviewed. Information on paternal occupation was
      available for 14,869 children dying from cancer in England, Wales, and Scotland
      in the period 1953-81 and for an equal number of matched controls. The importance
      of fathers working, at any time before or after conception of the survey child,
      in any of the following occupations was assessed: radiologists (clinical),
      surgeons and anesthetists, veterinary surgeons, dental surgeons, nuclear industry
      workers, industrial radiographers. There was no indication that preconception
      employment in any of these occupations was more important than postconception
      employment with regard to the risks of all childhood cancers or all childhood
      leukemias. Findings were consistent with neither paternal preconception exposure
      to external ionizing radiation nor exposure to unsealed sources of radionuclides
      being an important risk factor for childhood leukemia or for the overall grouping
      of all childhood cancers.

PMID- 7573077
TI  - High frequency of metalworkers among patients with seminomatous tumors of the
      testis: a case-control study.
AB  - Occupational analyses were conducted between 1971 and 1978 comparing 165 cases of
      testicular cancer in the Hannover region of Germany with 187 controls without
      neoplastic diseases admitted to the Hannover University Medical School during the
      same period. The results showed a significantly higher risk of metal workers
      developing seminomas and mixed seminomatous tumors compared to the controls (odds
      ratio 2.05; 1.17-3.58). There was a lack of risk for the nonseminomatous tumors
      as a whole group, and cases with a history of metal work may have a decreased
      risk for embryonal carcinomas. No definite single noxious substance responsible
      for the development of testicular tumors could be detected. In view of the
      results in animal experiments, cadmium and zinc are especially considered in the
      discussion.

PMID- 7573078
TI  - Glove-induced dermal and respiratory symptoms among health care workers in one
      Finnish hospital.
AB  - To evaluate the prevalence of skin and respiratory symptoms associated with the
      use of protective gloves in health care workers, an inquiry study was carried out
      on 534 hospital employees who used protective latex or vinyl gloves on a daily
      basis at work. The prevalence of skin disorders related to the usage of gloves
      was 56%. Rhinorrhea or nasal congestion was present in 13% of the workers who
      used powdered disposable gloves. The prevalence of both skin and respiratory
      symptoms was significantly higher among the workers who used gloves > 2 hours a
      day (p < 0.001). The skin disorders were more common in young employees. The
      findings indicate that most of the symptoms were caused by irritation or an
      immediate, IgE-mediated allergy. We conclude that there is a positive correlation
      between the duration of daily glove usage at work and the skin and respiratory
      symptoms. In order to reduce skin disorders associated with the daily use of
      gloves, it is necessary to develop safer materials in the glove manufacturing
      process.

PMID- 7573080
TI  - The virtual health economy: telemedicine and the supply of primary care
      physicians in rural America.

PMID- 7573079
TI  - Respiratory effects of chronic hydrogen sulfide exposure.
AB  - A cross-sectional study investigated whether the exposure of sewer workers to
      hydrogen sulfide (H2S) was associated with reduced lung function. Sixty-eight
      sewer workers and 60 water treatment workers performed spirometric tests. Job
      titles were used to classify the sewer workers according to presumed H2S
      exposure, and water treatment workers served as a comparison population presumed
      to have no occupational exposure to H2S. There was a statistically significant
      difference in mean FEV1/FVC values between sewer and water treatment workers of
      similar age, height, race, and smoking habits (-3.1, s.e. = 1.4). This deficit
      was greatest (-5.7, s.e. = 2.0) for sewer workers presumed to have high H2S
      exposure. Nonsmoking sewer workers presumed to have high H2S exposure achieved
      only 89% of their predicted FEV1/FVC value, whereas nonsmoking water treatment
      workers achieved nearly 98% of their predicted FEV1/FVC value. In conclusion,
      this study found evidence that chronic low level exposure to H2S may be
      associated with reduced lung function.

PMID- 7573081
TI  - In camera inspections of privileged records in sexual assault trials: balancing
      defendants' rights and state interests under Massachusetts's Bishop Test.

PMID- 7573082
TI  - Physicians & AIDS: discrimination and the Rehabilitation Act--Doe v. Attorney
      General.

PMID- 7573083
TI  - Legal & ethical safeguards: protection of society's most vulnerable participants
      in a commercialized organ transplantation system.

PMID- 7573084
TI  - Regional harmonization of occupational health rules: the European example.
AB  - This study of the occupational health law of the European Union looks first at
      the jurisdiction of the Union and the history and scope of its legislation in
      this area. The main body of the Article examines the level of protection that is
      afforded to the workforce under European Union law. The Article first considers
      the way in which assessment of risk is handled and then passes on to measures
      that are provided for both preventing and protecting against health risks. It
      notes the greater role given to protection. The Article also mentions the
      ancillary measures that are destined to make both prevention and protection
      effective. Finally, it looks at the Union's detailed provisions for worker
      involvement in occupational health matters and the more meager ones on employment
      rights and compensation. The Article ends with a discussion of the problems faced
      by the Union in enforcing its rules and an assessment of the strengths and
      weaknesses of the European Union's occupational health law. It is suggested that,
      overall, it deserves a positive judgment.

PMID- 7573085
TI  - How departments of internal medicine can prepare for new relationships in a
      capitated environment.

PMID- 7573087
TI  - Preeclampsia and postpartum renal failure: examples of pregnancy-induced
      microangiopathy.

PMID- 7573086
TI  - Leading academic internal medicine through education, discussion, and advocacy.

PMID- 7573088
TI  - Combined fractional excretion of sodium and urea better predicts response to
      saline in hyponatremia than do usual clinical and biochemical parameters.
AB  - BACKGROUND: The treatment of hyponatremic patients requires physicians to make a
      therapeutic choice between saline infusion and water restriction. Therefore, they
      need readily available and reliable parameters to facilitate making that choice.
      This study was designed to determine whether the use of clearance ratios can help
      clinicians recognize saline-responding hyponatremic patients. PATIENTS AND
      METHODS: Thirty-five nonedematous, hospitalized, hyponatremic patients were
      classified according to their history and saline response into four groups:
      diuretic-taking patients, polydipsic patients, saline responders, and saline
      nonresponders. Within these four groups, clinical and biochemical volume-related
      parameters, including clearance ratios, were prospectively evaluated before
      infusion of 2 L isotonic saline. Clearance ratios as well as usual clinical and
      biochemical parameters were tested for their accuracy in predicting saline
      responsiveness. RESULTS: Both positive (70%) and negative (54.5%) predictive
      values for hypovolemia were unsatisfactory; clinical prediction of hypovolemia
      was also characterized by low sensitivity (41.1%), but acceptable specificity
      (80%). In the polydipsia and saline-nonresponder groups, plasma urea and uric
      acid values tended to be lower than in the diuretic and saline-responder groups.
      However, the usefulness of these parameters was limited by too large an overlap
      among the different groups. In both polydipsic patients and saline responders,
      urinary sodium concentration was low. The combined amount of urinary sodium and
      potassium in relation to plasma sodium did not discriminate among the different
      groups. Most helpful in distinguishing among the groups was a combination of
      several clearance ratios (fractional excretions of sodium, potassium, urea, and
      uric acid), since the predictive use of each parameter on its own was restricted.
      The best indicator of saline responsiveness was a low fractional excretion of
      filtered sodium (< 0.5%) combined with a low fractional excretion of urea (<
      55%). CONCLUSION: The accuracy of clinical evaluation for predicting the state of
      extracellular fluid volume in hyponatremia is low. The combination of low
      fractional sodium excretion (< 0.5%) and low fractional urea excretion (< 55%) is
      the best biochemical way to predict saline response, whereas high fractional
      potassium excretion (> 20%) indicates diuretic intake.

PMID- 7573089
TI  - Earlobe crease in women: evaluation of reproductive factors, alcohol use, and
      Quetelet index and relation to atherosclerotic disease.
AB  - BACKGROUND: The diagonal earlobe crease (ELC) has been found to be associated
      with atherosclerotic heart disease. Although atherosclerotic cardiovascular
      disease is less prevalent among women than among men, no studies have been
      reported for women on the possible relationship of reproductive factors,
      contraceptive and menopausal estrogen use, and alcohol use on the expression of
      the ELC. SUBJECTS AND METHODS: The presence of ELC was determined in 625 white
      women who were seen as part of a breast research project. Information was
      obtained on age, height, weight, age at menarche, parity, age at first full-term
      pregnancy, use of oral contraceptives or menopausal estrogens, alcohol
      consumption, and smoking. Statistical methods used included estimation of the age
      adjusted odds ratios and their 95% confidence intervals, and multiple logistic
      regression. RESULTS: No association was found between the ELC and reproductive
      factors and smoking. Only age, Quetelet index, and alcohol use were associated
      with the ELC. The ELC was negatively associated with alcohol use, and was more
      marked in women under 59 years of age. The positive association of ELC with the
      Quetelet index progressively became more marked with advancing age, especially
      after 60 years of age. CONCLUSION: The negative association found between the ELC
      and alcohol use is of interest because of the reported protective effect of
      moderate alcohol consumption on risk of coronary heart disease. No significant
      association was found between the ELC and reproductive risk factors. Based on
      events occurring during the embryonic development of the earlobes, a new
      hypothesis is proposed for the formation and peculiar diagonal localization of
      the ELC in adult earlobes in association with atherosclerotic vascular disease.

PMID- 7573091
TI  - Reduction of cortisol levels after single intra-articular and intramuscular
      steroid injection.
AB  - BACKGROUND: This study was undertaken to determine the influence of single intra
      articular or intra muscular injections of methylprednisolone acetate on the
      hypothalamic-pituitary-adrenal axis. PATIENTS AND METHODS: Twenty-one patients
      with rheumatic disease who had never been treated with systemic glucocorticoids
      and had not received local injections of these agents for the preceding 2 months,
      were given 40 mg of methylprednisolone acetate. Group I (11 patients) received
      one intra-articular injection into the knee, and Group II (10 patients) received
      the same dose intramuscularly. RESULTS: In Group I, serum cortisol levels were
      significantly decreased 24 hours after injection (228.2 +/- 8.7 nmol/L versus 193
      +/- 16.3 nmol/L; P < 0.05). Serum cortisol levels were decreased in 9 of the 11
      patients, by an average of 21.5%. Two patients' levels were below 138 nmol/L,
      which is considered to be the lower limit of normal range. Serum cortisol levels
      were below normal range in 3 patients 72 hours after intra-articular steroid
      injection. In Group II, serum cortisol levels were significantly decreased at 72
      hours after injection (239.6 +/- 10.3 nmol/L versus 175.6 +/- 21.4 nmol/L; P <
      0.01). Three patients' levels were below normal. By 72 hours postinjection, serum
      cortisol concentrations in 9 of 10 patients were decreased by an average of 31%
      compared to preinjection values. CONCLUSION: The present study suggests that
      decreased adrenocortical secretion, as reflected in depressed cortisol levels,
      can result from a single, low-dose, intra-articular or intramuscular injection of
      depot corticosteroids.

PMID- 7573092
TI  - The effect of fasting status on the determination of low-density and high-density
      lipoprotein cholesterol.
AB  - PURPOSE: To determine the effect of a self-selected meal on concentrations of low
      density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol
      (HDL-C) in a screening setting and to determine the effect of using nonfasting
      values to classify individuals according to National Cholesterol Education
      Program guidelines. SUBJECTS AND METHODS: Study subjects were 115 employees who
      had previously participated in worksite total cholesterol screening, selected by
      stratified random sampling for sex and total cholesterol levels. Total
      cholesterol, triglycerides, HDL-C, and estimated LDL-C were determined before
      subjects ate a self-selected breakfast and 3 and 5 hours after eating it.
      RESULTS: LDL-C values determined 3 and 5 hours following breakfast were
      approximately 7% and 2.5% lower, respectively, than fasting values. Use of 3-hour
      and 5-hour LDL-C determinations to classify individuals with elevated fasting
      levels (> or = 3.36 mmol/L) resulted in false-negative rates of 20% and 14%,
      respectively. Three- and 5-hour HDL-C values were approximately 4% and 1.5%
      lower, respectively, than fasting levels. Use of 3-hour HDL-C values to classify
      individuals with low fasting levels (< 0.91 mmol/L) resulted in no false
      negatives, whereas 1 of 7 individuals with low fasting HDL-C was misclassified
      when 5-hour values were used. CONCLUSIONS: These results support the 1993
      National Cholesterol Education Program guidelines that LDL-C levels should be
      determined only in fasting persons, and that nonfasting HDL-C values may be
      acceptable for screening purposes.

PMID- 7573090
TI  - Efficacy and safety of pravastatin in the treatment of patients with type I or
      type II diabetes mellitus and hypercholesterolemia.
AB  - PURPOSE: Patients with type I and type II diabetes mellitus have an increased
      risk of coronary heart disease. In many diabetics, hypercholesterolemia is
      present and further exacerbates this risk. We investigated the efficacy and
      safety of pravastatin in the treatment of patients with type I or type II
      diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS: In this 24
      week, multi-center, double-blind, placebo-controlled study, 94 patients (45 men,
      49 women), 18 to 70 years of age, with type I or type II diabetes mellitus and
      hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol [LDL-C]
      levels > 150 mg/dL and above the 75th percentile for the US population by age and
      gender) were randomized to receive pravastatin 20 mg hs or matching placebo. Two
      patients were randomized to treatment with drug for every 1 randomized to
      placebo. The dose could be doubled after 10 weeks, and cholestyramine or
      colestipol could be added after 18 weeks, as needed, to attempt to lower the LDL
      C levels to below the 50th percentile for the US population. RESULTS: Significant
      reductions in LDL-C (-27.6%), total cholesterol (-22.1%), very-low-density
      lipoprotein cholesterol (-22.6%), and triglycerides (-12.8%) (P < or = 0.001
      versus placebo for all reductions), and significant increases in high-density
      lipoprotein cholesterol (4.4%) (P < or = 0.05 versus placebo) were noted in the
      pravastatin treatment group (average dose 29.5 mg) at 16 weeks. The beneficial
      lipid-lowering effects of pravastatin were maintained throughout the 24 weeks of
      the study. Pravastatin was well tolerated, and the frequency of side effects was
      similar in the pravastatin and placebo groups. No clinically significant changes
      in the control of diabetes, as assessed by fasting blood glucose levels and
      glycosylated hemoglobin measurements, were seen during this study. CONCLUSION:
      The results of this study demonstrate that pravastatin is well tolerated and
      effective in lowering total cholesterol and LDL-C in patients with type I or type
      II diabetes mellitus and hypercholesterolemia.

PMID- 7573094
TI  - Granulocytopenia after combined therapy with interferon and angiotensin
      converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.
AB  - PURPOSE: The purpose of this study was to assess whether granulocytopenia
      observed in 3 of 38 patients with essential mixed cryoglobulinemia who were
      treated with low-dose interferon was due to the underlying disease or to
      synergistic toxicity of interferon with other drugs. PATIENTS AND METHODS:
      Adverse effects of interferon therapy were monitored in 38 patients affected with
      type II essential mixed cryoglobulinemia. Patients were treated with 3 million
      units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35
      patients) or with natural interferon-beta (3 patients). The duration of treatment
      ranged between 6 and 15 months; the total duration of follow-up, including after
      therapy, ranged between 8 and 93 months. RESULTS: None of 35 patients treated
      with interferon alone developed significant hematologic alterations. In addition,
      none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors
      alone showed hematologic toxicity. Three patients who were treated with a
      combination of interferon and ACE inhibitors developed severe granulocytopenia a
      few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks
      after suspending therapy. Resumption of treatment with this drug combination
      produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon
      treatment alone, or ACE inhibitor monotherapy, was not followed by
      granulocytopenia. CONCLUSION: Although severe hematologic toxicity rarely
      develops in patients treated with low-dose interferon, granulocytopenia occurred
      in all 3 of our patients with mixed cryoglobulinemia who were treated with a
      combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug
      alone was toxic in any of our cryoglobulinemic patients, indicating a high risk
      of severe hematologic toxicity for this drug combination, at least in patients
      with this disease. Physicians should be aware of this danger when using
      interferon treatment in patients with this, or possibly other, disorder(s) that
      also require antihypertensive therapy.

PMID- 7573095
TI  - Lupus anticoagulant, heparin use, and thrombocytopenia in patients with chronic
      thromboembolic pulmonary hypertension: a preliminary report.
AB  - PURPOSE: An increased occurrence of thrombotic events has been described in
      patients exhibiting a lupus anticoagulant (LA). In patients with chronic, major
      vessel thromboembolic pulmonary hypertension, not only has there been a
      relatively high frequency of the LA, but also an unexpected association with
      heparin-related thrombocytopenia. This retrospective report emphasizes the
      frequency of this association. PATIENTS AND METHODS: We retrospectively reviewed
      the medical records of 216 patients admitted to the University of California, San
      Diego, Medical Center who were being considered for surgical correction of their
      chronic thromboembolic pulmonary hypertension. For each patient, the following
      information was sought: presence of an LA, variation in platelet numbers during
      the preoperative evaluation, and determination of whether an observed
      thrombocytopenia was related to heparin use. RESULTS: An LA was found in 23 of
      the 216 patients (10.6%). Of the remaining patients, sufficient platelet data for
      comparison were available for 68 patients. These 68 patients constituted the
      control group. Within the LA group, platelet counts during the preoperative
      evaluation declined to 51.6% +/- 16.7% of baseline counts, a highly significant
      difference (P < 0.0001) compared with the non-LA control group, who underwent a
      comparable evaluation with similar heparin exposure. In addition, heparin
      associated thrombocytopenia developed in 13 of the 23 LA patients (56.5%) and in
      none of the control patients. Heparin-induced arterial thrombosis was implicated
      as the cause of a myocardial infarction in 1 of the patients with heparin
      associated thrombocytopenia. CONCLUSIONS: In patients with chronic thromboembolic
      pulmonary hypertension, a high incidence of the LA and an accompanying
      association with heparin-related thrombocytopenia have been observed. Although
      further prospective studies of this relationship are needed, physicians should be
      alert to the possibility of thrombocytopenia when using heparin for patients
      exhibiting an LA.

PMID- 7573096
TI  - Association of antiphospholipid antibodies with central nervous system disease in
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the prevalence and characteristics of central nervous
      system disease in systemic lupus erythematosus (CNS/SLE) with particular
      reference to disease activity and to the presence of antiphospholipid (aPL)
      antibodies. PATIENTS AND METHODS: From 340 unselected SLE patients attending our
      lupus clinic, we found 96 (28%) to have definite CNS manifestations not
      attributed to any cause other than SLE. Patients with mild migraine or cognitive
      disorders were excluded. The control group consisted of 100 SLE patients without
      CNS or thromboembolic manifestations. RESULTS: Fifty-six of our CNS patients had
      transient ischemic attacks or strokes, 24 had epilepsy, and 12 had psychiatric
      disorders; the other 4 did not fulfill SLE criteria. In all, 55% of patients (53)
      were found to be positive for aPL antibodies, whereas only 20% of the SLE control
      group were positive (P < 0.001). Based on a physicians' global clinical
      assessment tool together with laboratory analysis, only 42 (44%) patients were
      found to be active at the onset of CNS manifestations, and the other 54 (56%)
      were nonactive. A finding of aPL antibodies was associated strongly with the
      inactive CNS/SLE group (P = 0.001). Of the 53 patients who underwent magnetic
      resonance imaging (MRI) study, 33 showed small high-density lesions suggestive of
      vasculopathy. Twenty-six (79%) of them were positive for aPL antibodies; whereas
      of the 20 patients with normal MRIs, only 8 (40%) were positive for aPL
      antibodies (P < 0.01). CONCLUSION: We confirm that CNS disease in SLE is
      significantly associated with the presence of aPL antibodies. The CNS
      manifestations can occur in about half of SLE patients without any other evidence
      of lupus activity. Abnormal MRIs highly correlate with positive aPL antibodies.

PMID- 7573097
TI  - Interferon-alpha therapy for chronic myelogenous leukemia.
AB  - PURPOSE: To provide a status report on the use of interferon (IFN)-alpha in
      patients with chronic myelogenous leukemia (CML). DATA SOURCES: Data on IFN-alpha
      therapy for CML collected from published articles identified in a MEDLINE
      computer search. RESULTS: Previously untreated patients with low-risk factors and
      early-stage disease consistently had the best results in clinical trials. A dose
      response was seen, with patients treated with dosages of 5 million units (MU)/m2
      per day showing the greatest incidence of cytogenetic remissions. In addition,
      randomized trials showed a survival advantage for IFN-alpha-treated patients. In
      studies comparing IFN-alpha therapy to chemotherapy, IFN-alpha produced
      significantly more major and durable cytogenetic responses than chemotherapy did.
      In studies combining IFN-alpha and chemotherapy, patients had significantly more
      cytogenetic responses, although more patient accrual and follow-up data are
      needed to offer conclusive statements concerning durability of response. IFN
      alpha also showed activity in maintaining remissions after both chemotherapy and
      bone marrow transplantation. CONCLUSIONS: IFN-alpha has significant activity in
      patients with CML, with best results at dosages of 5 MU/m2 per day. At these
      dosages, in patients with early-stage, Philadelphia+ CML, hematologic response
      rates of 70% to 80% and cytogenetic response rates of 50% (approximately 20% of
      which were complete) are seen. One randomized trial shows a survival advantage
      with cytogenetic response in IFN-alpha-treated patients, and this advantage
      appears to be unrelated to the degree of that response. These questions remain
      under study.

PMID- 7573093
TI  - The prevalence of side effects with regular and sustained-release nicotinic acid.
AB  - PURPOSE: To document the prevalence and nature of the side effects that occur
      with the use of regular and sustained-release nicotinic acid in everyday clinical
      practice. PATIENTS AND METHODS: One hundred and ten patients seen in a private
      medical clinic who were given 133 separate trials of nicotinic acid during a 5
      year period. The occurrence of side effects, particularly those severe enough to
      warrant discontinuing the drug, were carefully monitored. RESULTS: Forty-three
      percent of individuals given regular nicotinic acid and 42% of those given
      sustained-release nicotinic acid were forced to discontinue the medication
      because of side effects; some of these side effects necessitating discontinuing
      nicotinic acid did not occur until the patient had been taking the drug for 1 or
      2 years. CONCLUSION: Nicotinic acid in both regular and sustained-release forms
      is a powerful drug when used in doses needed to treat lipid disorders and causes
      disturbing side effects a very high percentage of the time. No one should use
      nicotinic acid in these doses without continued careful supervision of a
      physician.

PMID- 7573098
TI  - Misdiagnosis of erythema migrans.
AB  - BACKGROUND: Erythema migrans is a clinical diagnosis that carries possible long
      term repercussions. Despite widespread awareness of the clinical presentation of
      erythema migrans, incorrect diagnosis occurs. PATIENTS AND METHODS: We describe
      13 cases in which erythema migrans was misdiagnosed and discuss some pitfalls in
      diagnosis. These cases were seen at a tertiary referral center in Connecticut, a
      state where Lyme disease is endemic. The patients selected for inclusion were
      those who most clearly illustrate potential difficulties involved in making the
      diagnosis of erythema migrans. RESULTS: The diagnosis of erythema migrans was
      missed in 5 patients due to atypical presentations. Eight patients with skin
      eruptions closely mimicking erythema migrans were incorrectly diagnosed with
      erythema migrans. CONCLUSIONS: There are pitfalls associated with the diagnosis
      of erythema migrans that may result in overdiagnosis or underdiagnosis.

PMID- 7573099
TI  - Clinical implications of insulin resistance syndromes.
AB  - Epidemiologic studies have shown an association between higher insulin levels and
      coronary artery disease, and metabolic studies have associated insulin resistance
      and compensatory hyperinsulinemia with hypertension, obesity, and lipid
      disorders. This review focuses on the clinical implications (rather than the
      metabolic pathogeneses) of these associations and how practicing physicians
      should manage patients with insulin resistance.

PMID- 7573100
TI  - Art and the science of medicine.

PMID- 7573101
TI  - Myocarditis and subcutaneous granulomas in a patient with Crohn's disease of the
      colon.

PMID- 7573102
TI  - Verapamil-induced parkinsonism.

PMID- 7573104
TI  - Adult-onset celiac disease hidden by chronic steroid therapy for a skin disease.

PMID- 7573103
TI  - Hypercalcemia, sarcoidosis, and normal chest radiographs.

PMID- 7573105
TI  - Complaints attributed to chronic Lyme disease: depression or fibromyalgia?

PMID- 7573106
TI  - Gastrointestinal ulceration with NSAIDs.

PMID- 7573107
TI  - Gastrointestinal complications of nonsteroidal antiinflammatory drugs:
      prophylactic and therapeutic strategies.

PMID- 7573108
TI  - Beyond futility to an ethic of care.

PMID- 7573109
TI  - Splenic rupture in afibrinogenemia: conservative versus surgical management.

PMID- 7573110
TI  - Are laboratory measurements of folate adequate?

PMID- 7573111
TI  - Diagnostic value of fine-needle aspiration biopsy under ultrasonography.

PMID- 7573112
TI  - Upright tilt-table testing in the evaluation of syncope.

PMID- 7573113
TI  - Subsensitivity to the bronchodilator action of beta 2-adrenergic agonists.

PMID- 7573114
TI  - Bacteremia due to viridans streptococci in neutropenic patients.

PMID- 7573115
TI  - Prevention of intracellular adenosine triphosphate depletion after sublethal
      oxidant injury to rat type II alveolar epithelial cells with exogenous
      glutathione and N-acetylcysteine.
AB  - The alveolar epithelial cells of the lower respiratory tract are exposed
      continuously to injurious agents, including oxygen radicals. The type II alveolar
      epithelial cell is critically important to the normal function of the lung,
      because it is responsible for synthesis of surfactant and other essential duties.
      In the current investigation, the authors documented the loss of intracellular
      adenosine triphosphate (ATP) after exposure of the cells to sublethal
      concentrations of hydrogen peroxide (H2O2) and hypochlorous acid. Subsequent
      experiments attempted to alleviate or prevent this oxidant mediated loss of ATP
      by preincubating the cells with either glutathione or N-acetylcysteine (NAC).
      Initially, it was determined that exposure of the type II cells to 250 microM
      hypochlorous acid or 250 microM H2O2 for 1 hour each would cause significant loss
      of type II cell ATP. However, preincubation with glutathione (1,000 microM)
      inhibited the loss of ATP after both exposure to 250 microM H2O2 (24 +/- 3% loss
      of ATP without glutathione compared with 13 +/- 2% loss with glutathione, P <
      0.05), and 250 microM hypochlorous acid (12 +/- 2% loss of ATP without
      glutathione compared with 1 +/- 1% increase of ATP with glutathione). Similar
      results were obtained using NAC (2 mg/mL) after exposure to 250 microM H2O2 (23
      +/- 2% loss of ATP without NAC compared with a 4 +/- 3% loss of ATP with NAC).
      This study demonstrates that exogenous glutathione and NAC are able to protect
      type II cells from oxidant mediated sublethal injury and loss of intracellular
      ATP stores.

PMID- 7573116
TI  - Correlates of insulin autoantibodies with beta cell function at the time of
      diagnosis of diabetes mellitus.
AB  - In this article, the author discusses the prevalence of insulin autoantibodies
      (IAA) and endogenous insulin secretion in Saudi patients at the onset of
      diabetes. A positive result, defined as a value greater than 3 SD above the mean
      binding of normal, was found in 8 (7.6%) of 105 of the patients with diabetes and
      in 3 (5.7%) of 53 of the healthy control subjects. The relation between the
      presence of IAA and the pancreatic beta cell secretory activity was studied by
      determining the levels of insulin and C-peptide in the fasting state and 6
      minutes after intravenous injection of 1 mg glucagon. All the IAA positive
      subjects had a response to glucagon stimulation test. A positive correlation was
      found between basal and after stimulation for both insulin and C-peptide (r =
      0.79, P < 0.001; r = 0.85, P < 0.001 for insulin and r = 0.76, P < 0.001; r =
      0.81, P < 0.001 for C-peptide, respectively). Therefore, the current finding
      indicates that there is no direct effect of IAA on the pancreatic beta cell
      potential activity in Saudi patients with diabetes at the time of diagnosis,
      suggesting further that these patients have no insulin deficiency or have mild
      insulin dependency.

PMID- 7573118
TI  - Emergence of penicillin-resistant invasive pneumococci in a single American
      community.
AB  - Three decades ago, penicillin-resistant strains of Streptococcus pneumoniae were
      first reported. Since then, myriad penicillin resistant strains of S. pneumoniae
      have been identified worldwide and in the United States. No resistant or
      intermediate resistant strains have been reported in West Virginia because
      testing has not been done. Between 1983 and 1994, the authors' surveillance of
      invasive pneumococcal disease in metropolitan Huntington, West Virginia,
      identified 356 pneumococcal strains from blood and other usually sterile sites,
      including 110 strains belonging to serotypes 6, 9, 14, 19, and 23, the main
      serotypes exhibiting penicillin resistance. The authors tested these serotypes
      for penicillin susceptibility by the E-test. Sixteen (14.5%) strains of types 6,
      9, 14, 19, and 23 exhibited intermediate resistance to penicillin. No highly
      resistant strains were identified. Most of the intermediate resistant strains of
      types 9, 14, and 23 were detected in epidemiologic years 1992-1994. The
      increasing number of intermediate resistant penicillin strains signals the need
      for routine testing of invasive pneumococcal strains for penicillin
      susceptibility and necessitates appropriate antibiotic usage.

PMID- 7573117
TI  - Atrial natriuretic peptides and cyclic guanosine monophosphate metabolism.
AB  - Atrial natriuretic factor (ANF), consisting of amino acids 99-126 of the 126
      amino acid ANF prohormone, increases cyclic guanosine monophosphate (GMP)
      (thought to be the mediator of its physiologic effects) in plasma and urine of
      human subjects. Long-acting natriuretic peptide, vessel dilator, and kaliuretic
      peptide, consisting of amino acid 1-30, 31-67, and 79-98, respectively, of this
      same prohormone have natriuretic, diuretic, kaliuretic, and blood pressure
      lowering properties in humans. These three new peptide hormones increase cyclic
      GMP in vitro but were never investigated to determine whether they also cause
      extrusion of cyclic GMP from cells, resulting in an increase of cyclic GMP in
      plasma and/or urine. Infusion of each of these peptide hormones at their 100
      ng/kg body weight/min concentrations for 60 minutes into healthy humans resulted
      in a sevenfold increase in cyclic GMP in plasma and urine secondary to ANF, but
      no significant increase secondary to the other atrial peptide hormones. Based on
      the current data, ANF has a unique effect on the metabolism of cyclic GMP,
      causing it to be extruded from the cell, whereas the other three atrial peptides
      represent the more classical metabolism of cyclic GMP via cyclic GMP
      phophodiesterases.

PMID- 7573119
TI  - Case reports: recurrent hypertensive intracerebral hemorrhage.
AB  - Hypertensive intracerebral hemorrhage (ICH) usually is a one-time event, despite
      multiple microaneurysms and widespread lipohyalinosis in the cerebral perforating
      vessels. Contrary to this belief, the authors describe five patients with
      recurrent hypertensive ICH. Of 105 patients of spontaneous ICH, 5 had recurrence.
      All were patients with poorly controlled hypertension whose age ranged from 25-62
      years; 3 were women. Four patients had two episodes of ICH, and one had three. Of
      11 hemorrhages, 9 were ganglionic, one was pontine, and one was lobar. Recurrence
      of hypertensive ICH seems to be commoner than reported in the literature, and it
      may be attributed to poor control of blood pressure.

PMID- 7573120
TI  - Case report: testosterone treatment of systemic lupus erythematosus in a patient
      with Klinefelter's syndrome.
AB  - Systemic lupus erythematosus occurs with much greater frequency in females than
      in males, and in some reports, researchers suggested that treatment with
      androgenic hormones might have therapeutic effects in this disease. The authors
      report a case of systemic lupus erythematosus in a hypogonadal male with
      Klinefelter's syndrome who was treated with testosterone in doses sufficient to
      normalize the serum level of this hormone to the adult male range. Hematologic
      and serologic abnormalities, including elevated levels of anti-DNA antibodies and
      depressed complement levels, returned to normal within 9 months of increasing the
      testosterone dose. The findings in this patient indicate that androgenic steroids
      can exert significant effects on immune parameters, and suggest that effects of
      androgens on the immune system may contribute to the sexual dimorphism of
      autoimmune disease.

PMID- 7573121
TI  - Case report: analgesic nephropathy: a soda and a powder.
AB  - Analgesic nephropathy has long been considered a potentially preventable cause of
      renal disease. Early reports were described in patients who consumed analgesics
      containing phenacetin. In recent data, the removal of phenacetin from analgesic
      preparations resulted in a reduction in analgesic-induced end stage renal disease
      in Europe and Australia. However, a reduction in the incidence of analgesic
      nephropathy has not occurred uniformly, suggesting that phenacetin is not the
      sole cause. Current data raise concerns regarding adverse renal effects of
      acetaminophen and nonsteroidal antiinflammatory drugs. Aspirin taken alone may be
      of least concern. The diagnosis of analgesic nephropathy is suggested in subjects
      with chronic renal failure, a history of daily consumption of analgesic
      preparations, small bumpy kidneys, and renal papillary necrosis or chronic
      interstitial nephritis. However, the spectrum of disease may be changing, because
      these agents also may increase the risk of cardiovascular disease and chronic
      renal disease due to nephrosclerosis, glomerulonephritis, and diabetes mellitus.
      Potential pathogenetic mechanisms in analgesic nephropathy include direct
      cellular injury induced by analgesics, prostaglandin inhibition with reduction or
      redistribution of renal blood flow, and interesting new concepts regarding the
      role of caffeine in increasing oxygen demand and reducing oxygen supply in the
      medulla. The primary goal of therapy is discontinuation of analgesic consumption.
      Because of the association between analgesic intake and uroepithelial tumors,
      surveillance of patients for neoplasm is suggested.

PMID- 7573122
TI  - Review of the literature: severe hyperphosphatemia.
AB  - A patient with a markedly elevated serum phosphorus level (23.9 mg/dL) is
      described, followed by a brief review of severe hyperphosphatemia. Elevated serum
      phosphorus levels may be artifactual or true. True hyperphosphatemia is usefully
      subdivided according to (a) whether phosphorus is added to the extracellular
      fluid from a variety of exogenous or endogenous sources, or (b) whether the
      urinary excretion of phosphorus is reduced from either decreased glomerular
      filtration or increased tubular reabsorption. Severe hyperphosphatemia, defined
      herein as levels of 14 mg/dL or higher, is almost invariably multifactorial-
      usually resulting from addition of phosphorus to the extracellular fluid together
      with decreased phosphorus excretion. The hyperphosphatemia of the patient
      described herein appeared to result from a combination of dietary phosphorus
      supplementation, acute renal failure, acute pancreatitis, and ischemic bowel
      disease, complicated by lactic acidosis.

PMID- 7573124
TI  - Multiple herniae: a defect in the celomic mesoderm?
AB  - We report on a child with congenital bilateral cervical lung herniation with
      associated retrosternal (Morgagni), posterolateral (Bochdalek), esophageal
      hiatal, and inguinal herniae, and with multiple urinary bladder diverticuli.
      These multiple herniations may be secondary to a defect in the embryonic celomic
      mesoderm.

PMID- 7573125
TI  - Analysis of variability of clinical manifestations in Waardenburg syndrome.
AB  - Expression of clinical findings of Waardenburg syndrome type 1 (WS1) and type 2
      (WS2) is extremely variable. Using our collection of 26 WS1 and 8 WS2 families,
      we analyzed the occurrence, severity, and symmetry of clinical manifestations
      associated with WS. We found significant differences between WS1 and WS2 in
      deafness, and in pigmentary and craniofacial anomalies. Factor analysis was used
      to identify manifestations which covaried, resulting in 2 orthogonal factors.
      Since mean factor scores were found to differ when compared between WS1 and WS2,
      we suggest that these factors could be useful in distinguishing WS types. We
      found that the WS gene was transmitted from mothers more often than from fathers.
      We also extensively examined the W-Index, a continuous measure of dystopia
      canthorum. Our data suggest that use of the W-Index to discriminate between
      affected WS1 and WS2 individuals may be problematic since 1) ranges of W-Index
      scores of affected and unaffected individuals overlapped considerably within both
      WS1 and WS2, and 2) a considerable number of both affected and unaffected WS2
      individuals exhibited W-index scores consistent with dystopia canthorum.
      Misclassification of families may have implications for risk assessment of
      deafness, since WS2 families have been reported to have greater incidence of
      deafness, as confirmed in our study.

PMID- 7573126
TI  - Association between alleles of the transforming growth factor alpha locus and
      cleft lip and palate in the Chilean population.
AB  - Two RFLPs at the TGFA locus were studied in 39 unrelated Chilean (Caucasoid
      Mongoloid) patients with non-syndromic cleft lip/palate [CL(P)] and 51 control
      individuals. A highly significant association between BamHI A2 allele and CL(P)
      was detected (chi 2 = 6.00; P = 0.014), while no association was found between
      TaqI RFLPs and clefting. No significant differences were found when comparing
      genotypes by type of cleft and a positive or negative family history of clefting.
      Our results seem to support rather definitively the association between TGFA and
      clefting but do not support the hypothesis that TGFA is a major causal gene of
      CL(P).

PMID- 7573123
TI  - Cytogenetic and molecular analysis of a ring (21) in a patient with partial
      trisomy 21 and megakaryocytic leukemia.
AB  - We describe a patient with an asymmetric double ring 21 in mosaic form, 45,XX, 
      21/46, XX, -21, +r(21), who has limited manifestations of Down syndrome and who
      developed acute myelofibrosis and megakaryocytic leukemia (AMKL), FAB M7, a
      hematologic disorder particularly common in Down syndrome patients. In situ
      hybridization studies, gene dosage, and DNA polymorphism analysis showed that the
      ring chromosome carries a duplicated region which extends from D21S406 on the
      centromeric side and includes marker D21S3 on the telomeric side. FISH studies
      indicate two sizes of ring 21 in the patient. The origin of the supernumerary
      chromosome 21 in the proband was paternal; furthermore, the r(21) probably was
      formed postzygotically. Included in the duplicated segment are the candidate
      genes for leukemia AML-1, ETS, and ERG. The potential significance of disomic
      homozygosity of loci on 21q in M7 megakaryocytic leukemia is discussed.

PMID- 7573129
TI  - Interstitial duplication 19p.
AB  - We report on a 9-month-old girl with an interstitial duplication of 19p,
      developmental delay, and multiple anomalies including bifrontal prominence,
      obtuse frontonasal angle, short columella, additional midline philtral pillar,
      midline ridge on the tongue, vertical midline ridge at the mental symphysis, and
      a complex congenital heart defect including severe branch pulmonary artery
      stenosis, secundum atrial septal defect (ASD), and several ventricular septal
      defects (VSDs). Use of fluorescent in situ hybridization (FISH) with chromosome
      19-specific probes showed a direct duplication of bands 19p13.13 and 19p13.2.

PMID- 7573128
TI  - Small patella syndrome.
AB  - We report on 2 sporadic cases of small patella syndrome (coxo-podo-patellaire
      syndrome) most probably representing new mutations. Both children showed retarded
      patellar bone age (small patellae in Patient 1 and absent patellae in Patient 2)
      and pelvic abnormalities. Patient 1 who was fully investigated had an unusual
      facies with characteristic morphological abnormalities of the forefoot and
      generalized bone changes. Patient 2 was not available for examination and only X
      ray films of his knees, pelvis, and chest were available. These were all
      abnormal. He was said to have an "unusual facies" with flattened nose and
      prominent forehead but no further information was available. We think that small
      patella syndrome (coxo-podo-patellaire syndrome) is a generalized bone dysplasia
      with morphological and diagnostic radiographic appearances.

PMID- 7573127
TI  - Short tandem repeat polymorphism linkage studies in a new family with X-linked
      mental retardation (MRX20).
AB  - A family with X-linked recessive mental retardation (XLMR) without other obvious
      manifestations (MRX20) was studied with 14 short tandem repeat polymorphism
      (STRP) markers. Two-point lod scores above 3 were obtained with DXS1003, DXYS1,
      DXS3, and DXS458. A multipoint lod score of 4.25 was obtained with peak at
      DXS1003. Recombination events identify a 55.6 cM interval between DXS1068 and
      DXS454, while a one unit support interval identifies 40 cM between MAOA and
      DXS458.

PMID- 7573131
TI  - Patient with craniosynostosis and marfanoid phenotype (Shprintzen-Goldberg
      syndrome) and cloverleaf skull.
AB  - Marfanoid phenotype with craniosynostosis (Shprintzen-Goldberg syndrome) is a
      rare disorder previously described in only 5 patients. We report on the sixth
      known patient with this condition. The findings which distinguish our patient
      from others reported previously are that she was ascertained prenatally as having
      a cloverleaf skull; this is the first female patient described with this
      condition. Postnatally, she presented with arachnodactyly, camptodactyly, and
      clover-leaf skull. Imaging studies of the brain documented microcephaly with
      malformed brain, hydrocephaly, and hypoplasia of the corpus callosum. She also
      had choanal atresia and stenosis, a clinical finding previously reported only
      once, in this disorder.

PMID- 7573130
TI  - Distinct skeletal abnormalities in four girls with Shprintzen-Goldberg syndrome.
AB  - We describe 4 girls with Shprintzen-Goldberg syndrome. Skeletal abnormalities
      common to 3 of them include bowing of long bones (with a variable degree of
      progression over time), flare of the metaphyses, a large anterior fontanel with
      persistent patency into the second to fourth years of life, 13 pairs of ribs,
      distinct vertebral abnormalities which were absent neonatally but evolved by the
      second year of life, and progressive osteopenia. These abnormalities were
      generalized and, in one case, progressive over the first few years of life.
      Communicating hydrocephalus was present in all 4 cases. The eldest, an 11-year
      old girl, had additional anomalies not reported previously in this syndrome,
      including intestinal malrotation, an anteriorly placed anus, and mild cerebral
      atrophy. This is the first detailed report of skeletal manifestations in this
      rare disorder of unknown cause. These cases, in conjunction with a review of the
      literature, suggest that skeletal abnormalities are common in Shprintzen-Goldberg
      syndrome.

PMID- 7573133
TI  - Preliminary phenotypic map of chromosome 4p16 based on 4p deletions.
AB  - We have collected and analyzed clinical information from 11 patients with
      chromosome 4p deletions or rearrangements characterized by various molecular
      techniques. Comparing the extent of these patients' deletions with their
      respective clinical presentations led to the proposal of a preliminary phenotypic
      map of chromosome 4p. This map consists of regions which, when deleted, are
      associated with specific clinical manifestations. Nonspecific changes such as
      mental and growth retardation are not localized, and probably result from the
      deletion of more than one gene or region. The region associated with most of the
      facial traits considered typical in Wolf-Hirschhorn syndrome (WHS) patients
      coincides with the currently proposed WHS critical region (WHSCR), but some
      anomalies commonly seen in WHS appear to map outside of the WHSCR. The
      observation of clinodactyly in 2 patients with nonoverlapping deletions allows
      assignment of these defects to at least 2 separate regions in 4p16. These initial
      observations and attempts at genotype/phenotype correlation lay the groundwork
      for identifying the genetic basis of these malformations, a common objective of
      gene mapping efforts and chromosome deletion studies.

PMID- 7573132
TI  - De novo nonreciprocal translocation 1;8 confirmed by fluorescent in situ
      hybridization.
AB  - Constitutional nonreciprocal translocations are extremely rare, and even their
      existence is controversial. We report on a newborn infant with a de novo
      nonreciprocal translocation between chromosomes 1 and 8 resulting in 1q42.3
      deletion syndrome. Fluorescent in situ hybridization with whole chromosome paints
      confirmed the conventional cytogenetic diagnosis.

PMID- 7573134
TI  - Phenotypic mapping and clinical ideology.

PMID- 7573135
TI  - Interstitial deletions of the short arm of chromosome 4 in patients with a
      similar combination of multiple minor anomalies and mental retardation.
AB  - Interstitial deletions of chromosome 4 have been described rarely and have had
      variable presentations. We describe the phenotypic characteristics associated
      with interstitial deletion of the p14-16 region of chromosome 4 in 7 patients
      with multiple minor anomalies in common, and with mental retardation. A review of
      published cases of interstitial deletions of the short arm of chromosome 4 is
      provided. These deletions present a distinct phenotype which is different from
      that of Wolf-Hirschhorn syndrome.

PMID- 7573136
TI  - Gonadal dysgenesis in del(18p) syndrome.
AB  - We report on a girl with syndromal gonadal dysgenesis and a de novo del(18p).
      Genetic factors controlling gonadal development are located not only on the X
      chromosome, but also on autosomes. The present case suggests that one of these
      genes is situated on 18p. We conclude that patients with del(18p) syndrome should
      be evaluated for gonadal dysgenesis.

PMID- 7573137
TI  - Balanced reciprocal translocation mosaicism: how frequent?
AB  - We describe 2 cases of balanced reciprocal translocation (BRT) mosaicism. The
      frequency of this aberration in the population referred to our laboratory was
      determined and compared to those frequencies reported in the literature by other
      clinical cytogenetics laboratories. The extent of BRT mosaicism was also examined
      in surveys of parental populations, which are less likely to have a bias due to
      ascertainment on the basis of abnormal phenotype. the frequencies in the
      postnatal and prenatal populations examined in this study were calculated to be
      5.7 x 10(-5) (95% confidence interval is 3.2-8.2 x 10(-5)) and 4.1 x 10(-5) (95%
      confidence interval is 2.0-6.2 x 10(-5)). However, in view of the extent of
      variation reported in the various studies, these estimates should be considered
      first approximations of the true frequency.

PMID- 7573138
TI  - Autosomal dominant osteosclerosis type Stanescu: the third family.
AB  - We describe a family with Stanescu osteosclerosis. The propositus and his mother
      were short and had cortical sclerosis of the long bones, deficient facial sinus
      development, cranial bone malformations, and normal intelligence. To the best of
      our knowledge, only two such families have been described previously. The
      autosomal dominant pattern of inheritance of this skeletal dysplasia is
      reinforced, as there are many other reportedly affected relatives, including the
      maternal grandfather, uncles, and aunts of the propositus. The findings of
      wormian bones and calcification of the falx, not previously described, may be
      added to the phenotype.

PMID- 7573139
TI  - CHARGE association in a child with de novo inverted duplication (14)(q22-
      >q24.3).
AB  - We report on a 4-1/2 year old girl with apparent CHARGE association who had a de
      novo inverted duplication (14)(q22-->24.3), iris colobomas, ventricular septal
      defect, soft tissue choanal atresia, intellectual impairment, growth retardation,
      sensorineural deafness, apparently low set ears, and upslanting palpebral
      fissures. Family history was unremarkable and parental chromosomes were normal.
      Similarities between this and previously reported cases of 14q duplication
      suggest that a locus for a gene or genes causing some of the anomalies of CHARGE
      association may reside in the region 14q22 to 24.3.

PMID- 7573140
TI  - Rapid molecular cytogenetic analysis of X-chromosomal microdeletions:
      fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency.
AB  - Diagnosis of X-chromosomal microdeletions has relied upon the traditional methods
      of Southern blotting and DNA amplification, with carrier identification requiring
      time-consuming and unreliable dosage calculations. In this report, we describe
      rapid molecular cytogenetic identification of deleted DNA in affected males with
      the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and
      female carriers for this disorder. CGKD deletions involve the genes for glycerol
      kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We
      report an improved method for diagnosis of deletions in individuals with CGKD and
      for identification of female carriers within their families, using fluorescence
      in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol
      kinase gene. When used in combination with an Xq control probe, affected males
      demonstrate a single signal from the control probe, while female carriers
      demonstrate a normal chromosome with two signals, as well as a deleted chromosome
      with a single signal from the control probe. FISH analysis for CGKD provides the
      advantages of speed and accuracy for evaluation of submicroscopic X-chromosomal
      deletions, particularly in identification of female carriers. In addition to
      improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more
      readily available.

PMID- 7573144
TI  - Premature infant with Wiedemann-Beckwith syndrome: postnatal changes in facial
      appearance and somatic phenotype.

PMID- 7573141
TI  - Satoyoshi syndrome: an unusual postnatal multisystemic disorder.
AB  - Satoyoshi syndrome is a rare disorder of unknown cause characterized by
      progressive, painful intermittent muscle spasms, malabsorption, alopecia,
      amenorrhea, and skeletal abnormalities mimicking a skeletal dysplasia. We
      describe a 19-year-old Caucasian woman with characteristic manifestations
      starting at age 9. The report of this patient confirms that this condition is not
      limited to the Asian population.

PMID- 7573143
TI  - Removing the shadow of the law from the debate about genetic testing of children.
AB  - When physicians view efforts to obtain genetic testing for children as unwise or
      contrary to the children's interests, they face difficult problems both of ethics
      and of communicating with the parents. Contrary to the suggestions of some, the
      law has little to say about how physicians resolve these dilemmas. Parents do not
      have a constitutionally protected right to demand that unwilling physicians
      perform these tests. In addition, there is little risk of liability for damages
      unless the child suffers physical harm as a result of the physician's refusal to
      do the test. The debate about genetic testing of children needs to take place
      with a clear understanding of the law's limited impact.

PMID- 7573142
TI  - Association of kyphomelic dysplasia with severe combined immunodeficiency.
AB  - Kyphomelic dysplasia is a distinct, rare, skeletal dysplasia with short angulated
      femora, bowing of long bones, short ribs, narrow thorax, and metaphyseal
      abnormalities. While immune deficiency occurs in other short stature/short-limb
      skeletal dysplasias and cartilage-hair hypoplasia, it has not been described with
      kyphomelic dysplasia. We report on an infant with this disorder who had profound
      humoral and cellular immunologic abnormalities consistent with severe combined
      immune deficiency (SCID). The infant died at age 2 months of overwhelming
      cytomegalovirus pneumonia. Kyphomelic dysplasia, as with other short
      stature/short-limb skeletal dysplasias, can be associated with immune deficiency
      and immune function should be investigated when this disorder is identified.

PMID- 7573145
TI  - Skewed X-inactivation in a tumor tissue from a female patient with
      leiomyomatosis.

PMID- 7573146
TI  - Fluorescent in situ hybridization for evaluation of Prader-Willi and Angelman
      syndromes.

PMID- 7573147
TI  - Wiedemann-Beckwith syndrome, Wilms tumor, birth weight, and insulin-like growth
      factor 2.

PMID- 7573150
TI  - Anophthalmos-syndactyly (Waardenburg) syndrome without oligodactyly of toes.
AB  - We report on 2 brothers from a consanguineous family from a small city of
      southeast Turkey. Both have bilateral anophthalmia, soft tissue syndactyly of the
      feet, bilateral partial synostosis of metatarsals IV and V, and basal synostosis
      of the fourth and fifth toes on the right in the older sib only, thus differing
      from all previously reported cases of anophthalmos-syndactyly syndrome.

PMID- 7573151
TI  - Kaufman oculocerebrofacial syndrome in a girl of 15 years.
AB  - Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder
      characterized by severe mental retardation, microcephaly, long narrow face,
      ocular anomalies, and long thin hands and feet. To our knowledge only 8 cases
      have been reported so far, diagnosed at a mean age of 10 years. We report on a
      girl who was diagnosed at 15 years. Further phenotypic delineation is needed to
      improve diagnosis of this syndrome early in life.

PMID- 7573149
TI  - Apparent Malpuech syndrome: report on three Brazilian patients with additional
      signs.
AB  - We report on 3 unrelated Brazilian patients with shortness of stature,
      hypertelorism, eye anomalies, facial clefting, hearing loss, urogenital
      abnormalities, omphalocele, "caudal appendage," and mental retardation. Two
      patients were born to normal and non-consanguineous parents and one was born to
      consanguineous (first cousin) parents (F = 1/16). The similarity of our patients
      with those previously reported by Malpuech et al. [Am J Med Genet 16:475-480,
      1983] led us to suggest that they have the same condition.

PMID- 7573148
TI  - Albright hereditary osteodystrophy and del(2) (q37.3) in four unrelated
      individuals.
AB  - Albright hereditary osteodystrophy (AHO) is a condition with characteristic
      physical findings (short stature, obesity, round face, brachydactyly) but
      variable biochemical changes (pseudohypoparathyroidism,
      pseudopseudohypoparathyroidism). Most patients with AHO have decreased activity
      of the guanine nucleotide-binding protein (GS protein) that stimulates adenylyl
      cyclase. The gene encoding the alpha subunit of the GS protein (GNAS1) has been
      mapped to the long arm of chromosome 20. We describe 4 unrelated individuals with
      apparent AHO, associated with small terminal deletions of chromosome 2. All 4
      patients had normal serum calcium levels consistent with
      pseudopseudohypoparathyroidism. Del(2) (q37) is the first consistent karyotypic
      abnormality that has been documented in AHO [Phelan et al., 1993: Am J Hum Genet
      53:484]. The finding of the same small terminal deletion in 4 unrelated
      individuals with a similar phenotype suggests that a gene locus in the 2q37
      region is important in the pathogenesis of Albright syndrome. The association of
      Albright syndrome and the GNAS1 locus on chromosome 20 is well documented. The
      observation of a second potential disease locus on chromosome 2 may help explain
      the heterogeneity observed in this disorder.

PMID- 7573153
TI  - Hereditary disorders among Iranian Jews.
AB  - Iranian Jews represent an ancient community with a very high degree of
      inbreeding. Although the community remained relatively isolated, it had strong
      ties with Babylonian Jewry in Iraq. Several genetic disorders have been reported
      to be frequent among Iranian Jews, in particular, corticosterone methyloxydase
      deficiency type II, polyglandular syndrome, and rimmed vacuole myopathy. Based on
      the data collected in our clinic, recessive and dominant deafness also appear to
      be frequent. Other diseases, such as beta-thalassemia, achromatopsia,
      colobomatous microphthalmia, Dubin-Johnson syndrome, and congenital myasthenia
      gravis, were frequent in both the Iranian and Iraqi Jewish communities. The place
      of origin of the families within Iran and the results of molecular studies
      suggest some reason(s) for the high frequency of these disorders among Iranian
      Jews. While the high frequency of some of the disorders, such as corticosterone
      methyloxydase deficiency type II, represents a founder effect, in other diseases
      (such as beta-thalassemia) it was secondary to heterozygote advantage.

PMID- 7573154
TI  - Photoanthropometric study of craniofacial traits of individuals with Prader-Willi
      syndrome.
AB  - A photoanthropometric method, which enables an objective description of facial
      structures, was used to better delineate the craniofacial characteristics of 37
      individuals with Prader-Willi syndrome (PWS; 21 males and 16 females; 22 with
      15q11q13 deletions and 15 with normal-appearing chromosome 15s) between the ages
      of 0 to 12 years. Facial parameters were measured from strict frontal and profile
      photographic 35 mm slides and compared with other facial measurements from the
      same face (e.g., palpebral fissure width to bizygomatic diameter). We studied 16
      photoanthropometric craniofacial indices following the protocols established by
      Stengel-Rutkowski et al. [1984: Hum Genet 67:272-295] and Butler et al. [1988: Am
      J Med Genet 30:165-168]. Based on our measurements of 37 Prader-Willi syndrome
      individuals, none of the parameters were consistently outside of the normal range
      when compared with photoanthropometric index standards for age established from
      white control children [Stengel-Rutkowski et al., 1984]. However, several
      suggestive findings were documented by our analysis including: narrow palpebral
      fissure width [particularly in older children (6-12 years)], high midface, broad
      interalar distance, short back of the nose, prominent high chin, and broad low
      set ears. No significant differences were found in craniofacial parameters
      between deletion or nondeletion Prader-Willi syndrome patients with this
      methodology. These craniofacial parameters (many not previously evaluated in PWS
      patients) may become useful for early detection, and aid in the diagnosis and the
      study of the development of the characteristic face seen in Prader-Willi
      patients.

PMID- 7573152
TI  - Infantile sialic acid storage disease: biochemical studies.
AB  - Infantile free sialic acid storage disease (ISSD), is an inherited metabolic
      disorder characterized by hyperexcretion of free sialic acid in the urine and by
      its storage in the lysosomes of different tissues. In order to obtain more
      reliable data on the amount of total and free sialic acid, we analyzed the urine,
      brain, cerebellum, liver, spleen, and kidneys from a 3-month-old baby who died
      with a diagnosis of ISSD. The lysosomal nature of the disease was confirmed by an
      electron microscopic study of cells in culture. No significant abnormalities were
      found involving cholesterol, total phospholipids, glycolipids, and gangliosides
      in the tissues examined. However, differences in the tissue distribution of
      individual glycolipids and gangliosides were observed. The amount of free and
      total sialic acid was markedly increased, due to the storage of free sialic acid
      accompanied by its hyperexcretion in the urine. These results demonstrate and
      confirm that only acid monosaccharide transport from the lysosome compartment is
      involved in the pathogenesis of ISSD.

PMID- 7573155
TI  - Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q.
AB  - Deletion 11q23-->qter and duplication 12q23-->qter are described in a boy with
      neuroblastoma, multiple congenital anomalies, and mental retardation. The patient
      has clinical manifestations of 11q deletion and 12q duplication syndromes. The
      possible involvement of the segment 11q23-->24 in the cause of the neuroblastoma
      is discussed.

PMID- 7573156
TI  - Partial trisomy 13q identified by sequential fluorescence in situ hybridization.
AB  - We report on a 19-month-old boy with partial trisomy 13q resulting from a
      probable balanced translocation involving chromosomes 1 and 13. The infant
      presented with omphalocele, malrotation, microcephaly with overriding skull
      bones, micrognathia, apparently low-set ears, rocker-bottom feet, and congenital
      heart disease, findings suggestive of trisomy 13. Karyotypic studies from
      peripheral blood lymphocytes documented an unbalanced karyotype 46,XY,-1,+der(1).
      The mother's chromosomes were normal, and the father was not available.
      Conventional cytogenetic techniques were unable to identify the extra material on
      the terminal 1q. Using fluorescence in situ hybridization (FISH) on the GTL
      banded metaphases, the extra material on 1q was identified as the terminal long
      arm of 13, thus resulting in partial trisomy 13 (q32-qter).

PMID- 7573157
TI  - Identical twins with Cohen syndrome.
AB  - We report the first case of identical female twins who satisfy the proposed
      diagnostic criteria for Cohen syndrome. The sisters presented with retinal
      degeneration, obesity and mental retardation, and had the characteristic facial
      appearance. The manifestations of previously reported cases of Cohen syndrome are
      reviewed. Unusual changes in our patients include tall stature, macrocephaly, and
      transient cardiomyopathy during the first year of life. These anomalies have been
      reported previously in other patients with Cohen syndrome, and suggest that the
      disorder is phenotypically heterogeneous. Precocious puberty was present in both
      girls; the latter findings have not been reported previously in the Cohen
      syndrome. Detailed metabolic and cytogenetic analysis demonstrated no
      abnormalities.

PMID- 7573158
TI  - Are we all of one mind? Clinicians' and patients' opinions regarding the
      development of a service protocol for predictive testing for Huntington disease.
      Canadian Collaborative Study for Predictive Testing for Huntington Disease.
AB  - There are currently different research programs in place to assess the effects of
      predictive testing for a few late-onset disorders, including Huntington disease
      (HD) and familial cancers. Prior to providing predictive testing as a service, we
      sought the views of both the patients and the clinicians as to the importance and
      value of different items in a research protocol for HD. We mailed questionnaires
      to 41 clinicians and 351 at-risk patients who had participated in the research
      protocol, to solicit their opinions on the relative importance of various
      components of the HD predictive testing research protocol. Completed
      questionnaires were received from 256 patients (73%) and 33 clinicians (80%).
      Most participants (96%) were satisfied with the program, and < 3% of persons
      receiving a modification of risk felt that predictive testing had impaired their
      quality of life. While there was consensus on the importance of most components
      of the protocol, significantly more clinicians than patients (97% vs. 72%; P =
      0.02) felt it was essential to keep written material about HD as part of a
      service protocol. More patients than clinicians (83% vs. 27%) considered it
      essential to have 24-hr contact numbers following disclosure of test results (P <
      0.0001). Patients also felt more strongly about the importance of counseling
      about technical aspects of predictive testing (84% vs. 77%; P < 0.02), and about
      having a support person attend counselling sessions with the patient (62% vs.
      48%; P = 0.04). Nearly 25% of participants indicated that they would not want
      their general practitioner routinely involved in the predictive testing program.
      These findings have influenced the development of our service protocol, and they
      underscore the importance of involving both providers and consumers of predictive
      testing in the development of a service protocol for genetic testing.

PMID- 7573159
TI  - Pelizaeus-Merzbacher disease caused by a de novo mutation that originated in exon
      2 of the maternal great-grandfather of the propositus.
AB  - Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder of the
      central nervous system. Many cases of PMD can be attributed to defects in the
      proteolipid protein gene (PLP). To date, with one exception, each family has had
      either no or a unique mutation in one of the seven exons of PLP. We describe a
      new missense mutation in exon 2 of the PLP gene of an affected individual. This
      mutation codes for Ile instead of Thr at codon 42. The point mutation originated
      in the X chromosome of the maternal great-grandfather of the propositus. This was
      determined from the pattern of inheritance of the AhaII polymorphism and a series
      of microsatellite markers that are localized near PLP at Xq22.

PMID- 7573160
TI  - Ullrich-Turner syndrome: neurodevelopmental changes from childhood through
      adolescence.
AB  - Our objective was to investigate whether the previously-described neurocognitive
      pattern in girls with Ullrich-Turner syndrome is found in childhood and
      adolescence; we used a prospective, controlled study of neurocognitive
      development in girls with Ullrich-Turner syndrome. The patients included 56 girls
      with Ullrich-Turner syndrome, and 100 normal age- and verbal IQ-matched female
      control subjects, whose ages ranged from 6-14 years. All girls with Ullrich
      Turner syndrome and the normal control girls received a battery of neurocognitive
      tests designed to evaluate the following domains: general cognition, memory,
      academic achievement, language, visual-spatial/perceptual skills, visual-motor
      skills, attention, and affect recognition. Our results demonstrated consistent
      findings in Ullrich-Turner syndrome girls across the age range studied. In
      general, the Ullrich-Turner girls resembled control subjects in terms of verbal
      and language abilities. We found relatively depressed performance IQ and a
      significant verbal IQ-performance IQ difference. Significant differences were
      observed on examination of nonverbal abilities. The Ullrich-Turner girls
      performed more poorly than control girls on 1) tests of visual-motor skills
      including the Beery Test of Visual-Motor Integration, the Perceptual Organization
      Factor, and the Rey-Osterrieth Figures; 2) tests of visual-spatial skills,
      including the Motor-Free Visual Perception Test; 3) tests of attention, including
      the Freedom From Distractibility Factor; and 4) the Affective Prosody Affect
      Recognition Test. Ullrich-Turner subjects showed evidence of multifocal or
      diffuse right cerebral dysfunction and deficits generally involving nonverbal
      skills that may be due to X chromosome monosomy, gonadal dysgenesis, or both.
      Future studies will examine the role of estrogen replacement on cognitive
      function in Ullrich-Turner syndrome individuals.

PMID- 7573161
TI  - Velo-facio-skeletal syndrome in a mother and daughter.
AB  - We present a woman and her daughter with an apparently new short stature syndrome
      associated with facial and skeletal anomalies and hypernasality. Manifestations
      included hypertelorism with broad and high nasal bridge, epicanthal folds, narrow
      and high arched palate, mild mesomelic brachymelia, short broad hands, prominent
      finger pads, hyperextensibility of hand joints, small feet, nasal voice, and
      normal intelligence. The mother had short stubby thumbs and the daughter had
      posteriorly angulated ears and delayed bone age. The morphology of the nose and
      the hypernasality are reminiscent to those in the velo-cardio-facial syndrome.
      High resolution banding and fluorescent in situ hybridization studies showed no
      evidence of 22q11 deletions. Differentiation from Aarskog syndrome and Robinow
      syndrome is discussed.

PMID- 7573162
TI  - Trisomy 1q42 --> qter in a sister and brother: further delineation of the
      "trisomy 1q42 --> qter syndrome".
AB  - We report on a 22-year-old woman and her 21-year-old brother with mild mental
      retardation, long face, prominent forehead, retrognathia, and (relative)
      macrocephaly. At birth they were small for date, their length is now below the
      10th centile. Chromosome analysis demonstrated a nearly pure trisomy 1q42 -->
      qter in both patients due to unbalanced segregation of a paternal reciprocal
      balanced translocation 46,XY,t(1;15) (q42;p11). This is the second report of a
      nearly pure trisomy 1q42 --> qter. When comparing the manifestations of our
      patients with those of other reported cases we conclude that the most
      characteristic clinical manifestations of this syndrome are macrocephaly,
      prominent forehead, micro/retrognathia, large fontanelle, intrauterine growth
      retardation, postnatal growth retardation, and mental retardation.

PMID- 7573163
TI  - GAPO syndrome: a new case.
AB  - The fifteenth known case of GAPO syndrome is presented: a probable autosomal
      recessive condition of growth retardation, alopecia, pseudoanodontia (failure of
      tooth eruption), and optic atrophy. This article contains the clinical report of
      a 9-year-old girl and a short review of the hitherto-known cases. The syndrome
      could be attributed to either ectodermal dysplasia or perhaps an accumulation of
      extracellular connective tissue matrix.

PMID- 7573164
TI  - Renal dysplasia associated with in utero exposure to gentamicin and
      corticosteroids.
AB  - We report on a patient with renal cystic dysplasia, whose mother was given
      gentamicin and corticosteroids early in pregnancy. We speculate that these drugs
      may be implicated in abnormal nephrogenesis in humans. This speculation is based
      on gentamicin-induced small kidneys (oligonephronia) in the rat. Renal cystic
      disease has been demonstrated following glucocorticoid administration early in
      gestation. We realize that there is no proof for a casual relationship between
      gentamicin and/or glucocorticoids in the pathogenesis of this patient's renal
      disease. However, it is possible that renal cystic dysplasia in humans is not
      solely the result of a genetic defect.

PMID- 7573165
TI  - Cutaneous manifestations of Apert syndrome.

PMID- 7573167
TI  - Type I bipolar disorder associated with a fragile site on chromosome 1.
AB  - The objective of this paper is to study the association between chromosomal
      fragile sites and type I bipolar disorder. This case-control study compares
      bipolar patients with normal controls. Ten cases of type I bipolar disorder
      diagnosed according to DSM-III-R criteria and the Composite International
      Diagnostic Interview (CIDI) were selected from the Escola Paulista affective
      disorders outpatient clinic and 10 healthy controls (CIDI negative for
      psychiatric diagnoses) matched for sex and age were drawn from the
      otorhinolaryngologic outpatient clinic of the same hospital. The cytogenetic
      analysis was carried out with blood lymphocytes, which were cultured in a folic
      acid-free medium. A total of 100 mitoses per subject were blindly analyzed to the
      psychiatric diagnostic assignment, and fragile sites were identified according to
      a minimum expected frequency of events per band in conformity with a Poisson
      distribution. A higher frequency of chromosomal lesions for cases than controls
      was found for the following bands: 1q32, 5q31, and 11q23, the 1q32 being
      considered a fragile site. Although no evident neuropsychiatric etiological
      component has been mapped to the 1q32 region so far, this finding may lead to
      further investigation of a possible linkage between genetic markers of this
      region and bipolar disorder.

PMID- 7573166
TI  - Atrioventricular canal and 3C (cranio-cerebello-cardiac) syndrome.

PMID- 7573168
TI  - Polymorphism and genetic mapping of the human oxytocin receptor gene on
      chromosome 3.
AB  - Centrally administered oxytocin has been reported to facilitate affiliative and
      social behaviours, in functional harmony with its well-known peripheral effects
      on uterine contraction and milk ejection. The biological effects of oxytocin
      could be perturbed by mutations occurring in the sequence of the oxytocin
      receptor gene, and it would be of interest to establish the position of this gene
      on the human linkage map. Therefore we identified a polymorphism at the human
      oxytocin receptor gene. A portion of the 3' untranslated region containing a 30
      bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a
      polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a
      sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected
      was used to map the the human oxytocin receptor to chromosome 3p25-3p26, in a
      region which contains several important genes, including loci for Von Hippel
      Lindau disease (VHL) and renal cell carcinoma.

PMID- 7573169
TI  - Spinocerebellar degeneration and cerebral hypomyelination in a family.
AB  - The proband is a 24-year-old woman who developed symptoms of a spinocerebellar
      degeneration in early childhood. Neurological examination revealed normal
      cognitive function, optic atrophy, dysarthria, titubation, action tremors,
      increased deep tendon reflexes, Babinski's signs, and a spastic scissoring gait.
      The magnetic resonance imaging (MRI) showed an abnormal increased signal on long
      TR images involving white matter throughout the cerebral hemispheres, most
      striking in the subcortical white matter, and to a lesser degree in the
      brainstem, compatible with diffuse hypomyelinating or dysmyelinating diseases.
      Metabolic and chromosomal studies were normal. Her 49-year-old mother developed
      similar symptoms in her 20s and is now wheelchair-bound. Findings on neurological
      examination and MRI were similar to her daughter but more severe. The proband's
      maternal grandfather had a female cousin who had a neurological illness beginning
      in her 20s with similar symptoms and signs and died at the age of 44 years.
      Spinocerebellar degenerations are a group of syndromes with similar clinical
      manifestations but heterogeneous etiology. We report a family with
      spinocerebellar degeneration with distinct MRI findings compatible with
      hypomyelination or dysmyelination which has not heretofore been described. This
      family may represent a new spinocerebellar syndrome due to an abnormality of as
      yet an undetermined gene.

PMID- 7573171
TI  - DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish
      alcoholics and controls.
AB  - The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in
      having a highly polymorphic gene structure that has been reported to produce
      altered receptor functioning. These allelic variations are caused by a 48-bp
      segment in exon III of the coding region which may be repeated from 2-10 times.
      Varying the numbers of repeated segments changes the length, structure, and,
      possibly, the functional efficiency of the receptor, which makes this gene an
      intriguing candidate for variations in dopamine-related behaviors, such as
      alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated
      for association with schizophrenia, bipolar disorder, Parkinson's disease, and
      chronic alcoholism, and all have been largely negative for a direct association.
      We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were
      alcoholics, many of the early onset type with features of impulsivity and
      antisocial traits. Genotype frequencies were compared to 113 Finnish controls who
      were free of alcohol abuse, substance abuse, and major mental illness. In 70
      alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major
      metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association
      was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF
      concentrations of the monoamine metabolites showed no significant difference
      among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics
      is the first to be conducted in a clinically and ethnically homogeneous
      population and to relate the DRD4 genotype to CSF monoamine concentrations. The
      results indicate that there is no association of the DRD4 receptor with
      alcoholism.

PMID- 7573170
TI  - Automated linkage analysis in psychiatric disorders.
AB  - A genome-wide search for linkage of microsatellite markers to chromosomal loci
      containing genes responsible for the major psychoses is a laborious task which
      can be carried out with greater speed and economy by introducing automation to
      several steps in the procedure. We describe the use of the Automated Linkage
      Preprocessor (ALP) program for the computer analysis of the waveform generated by
      fluorescein-labelled markers after electrophoretic separation. (To obtain a copy
      send a request to A.F. Brown at the below MRC address or use Anonymous FTP to
      ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP). The program runs on a PC in
      the Microsoft Windows environment, and is used in conjunction with an automated
      laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager software
      to detect and size the PCR products, filter out peaks of fluorescence due to
      nonallele fragments, and generate genotypes in a format suitable for direct input
      to standard linkage analysis programs. The method should offer the advantages of
      speed, accuracy, and reduced cost. Its use in linkage studies in a large family
      with manic-depressive illness is discussed.

PMID- 7573173
TI  - Central pontine myelinolysis as a complication of partial ornithine carbamoyl
      transferase deficiency.
AB  - Central pontine myelinolysis (CPM) is a demyelinating condition of the central
      pons with or without associated foci of demyelination in extrapontine areas. We
      present a case of partial ornithine carbamoyl transferase deficiency in a 5-year
      old girl which was complicated by CPM. The patient was a previously undiagnosed
      girl who presented with mild hyperammonemic encephalopathy with a maximum plasma
      ammonia level of 376 microM on admission. Laboratory testing established the
      diagnosis of OCT deficiency, and therapy with hydration and protein restriction
      was successful in returning the plasma ammonia levels to normal. Five days after
      correction of her hyperammonemia, the patient developed intractable seizures and
      coma. Serial MRI scans of the brain revealed the evolution of the characteristic
      findings of CPM. Plasma ammonia and electrolyte concentrations were well
      controlled throughout this time. This represents the first description of CPM in
      a patient with a urea cycle defect.

PMID- 7573172
TI  - Familial cosegregation of manic-depressive illness and a form of hereditary
      cerebellar ataxia.
AB  - We report on a Spanish family with cooccurrence of manic-depression and a form of
      hereditary cerebellar ataxia. All affected individuals in the second generation
      showed cerebellar ataxia and manic-depression simultaneously. Since anticipation
      has been described in both disorders and the pattern of segregation may be
      autosomal as well as X-linked, we have searched for a possible involvement of two
      candidate genes which are located either on an autosome (SCA1) or on the X
      chromosome (GABRA3). We concluded that expansion of trinucleotide repeats at SCA1
      gene cannot be considered as a disease-causing mutation, and this gene should be
      initially discarded.

PMID- 7573174
TI  - On the role of brain serotonin in expression of genetic predisposition to
      catalepsy in animal models.
AB  - The activity of the rate-limiting enzyme of serotonin biosynthesis, tryptophan
      hydroxylase, in the striatum but not in the hippocampus and midbrain of rats bred
      for predisposition to catalepsy was higher than in nonselected rats. Mice of the
      highly susceptible to catelepsy CBA strain also differed from other noncataleptic
      mouse strains by the highest tryptophan hydroxylase activity in the striatum.
      Inhibition of tryptophan hydroxylase with p-chlorophenylalanine and p
      chloromethamphetamine drastically decreased immobility time in hereditary
      predisposed to catalepsy animals. A decrease in the 3H-ketanserin specific
      binding in the striatum of cataleptic rats and CBA mice was found. It was
      suggested that this decrease in 5-HT2A serotonin receptor density represented a
      down regulation of the receptors due to an activation of serotonergic
      transmission in striatum. It is suggested that hereditary catalepsy may be
      resulted from genetic changes in the regulation of serotonin metabolism in
      striatum.

PMID- 7573175
TI  - Characteristics of familial aggregation in early-onset Alzheimer's disease:
      evidence of subgroups.
AB  - Characteristics of familial aggregation of Alzheimer's Disease were studied in 92
      families ascertained through a clinically diagnosed proband with an onset below
      age 60 years. In each family data were systematically collected on the sibships
      of the proband, of his father, and of his mother. A total of 926 relatives were
      included and 81% of the living relatives (i.e., 251 individuals) were directly
      examined. The estimated cumulative risk among first degree relatives was equal to
      35% by age 89 years (95% confidence interval 22 to 47%). This result does not
      support the hypothesis that an autosomal dominant gene, fully penetrant by age 90
      years, is segregating within all these pedigrees. Despite the fact that all
      probands were selected for an onset before age 60 years it was shown that two
      types of families could be delineated with respect to age at onset among affected
      relatives: all secondary cases with an onset below age 60 years were contributed
      by a particular group of families (type 1 families), whereas all secondary cases
      with an onset after age 60 years were contributed by another group of families
      (type 2 families). Although genetic interpretation of these findings is not
      straightforward, they support the hypothesis of etiologic heterogeneity in the
      determination of early-onset Alzheimer's disease.

PMID- 7573176
TI  - Structural change in dopamine D2 receptor gene in a patient with neuroleptic
      malignant syndrome.
AB  - Dysfunction of the dopaminergic system has been suggested as a pathogenic
      mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete
      coding sequences of the dopamine D2 receptor (DRD2) gene for structural
      abnormalities in 12 patients with a history of NMS, including two cases of
      familial NMS. Mutational analysis was performed by denaturing gradient gel
      electrophoresis (DGGE), a highly sensitive technique for detecting sequences
      differences. We found in one patient with a history of NMS a nucleotide
      substitution at codon 310 (CCG-->TCG) of exon 7 of the DRD2 gene which predicts
      the replacement of proline to serine in the third cytoplasmic loop of the
      receptor, a part of the receptor that interacts with G-proteins. A larger series
      of patients with NMS needs to be investigated to establish whether this allele is
      associated with an increased susceptibility to NMS.

PMID- 7573177
TI  - Search for a gene predisposing to manic-depression on chromosome 21.
AB  - Six kindreds containing multiple cases of Manic-depressive illness (MDI) were
      genotyped with seven highly polymorphic microsatellite loci used in the
      construction of an index map for chromosome 21. The kindreds were also genotyped
      with a microsatellite polymorphism for PFKL, a chromosome 21 locus that has shown
      suggestive linkage to MDI in one pedigree [Straub et al., 1993: The American
      Society of Human Genetics]. Evidence of linkage was not found assuming either
      autosomal dominant or recessive inheritance. The nonparametric affected sib pair
      test did not yield significant evidence of linkage.

PMID- 7573179
TI  - Magnetic resonance imaging of cerebral anomalies in subjects with resistance to
      thyroid hormone.
AB  - OBJECTIVE: Resistance to thyroid hormone (RTH) is an autosomal dominant disease
      caused by mutations in the human thyroid receptor beta gene on chromosome 3.
      Individuals with RTH have an increased incidence of attention deficit
      hyperactivity disorder (ADHD). The purpose of this study was to search for
      developmental brain malformations associated with RTH. METHOD: Forty-three
      subjects (20 affected males [AM], 23 affected females [AF]) with resistance to
      thyroid hormone and 32 unaffected first degree relatives (18 unaffected males
      [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric
      acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of six
      contiguous images beginning at a standard sagittal position lateral to the insula
      were analyzed by an investigator who was blind with respect to subject
      characteristics. The presence of extra or missing gyri in the parietal bank of
      the Sylvian fissure (multimodal association cortex) and multiple Heschl's
      transverse gyri (primary auditory cortex) were noted. RESULTS: There was a
      significantly increased frequency of anomalous Sylvian fissures in the left
      hemisphere in males with RTH (AM: 70%; AF: 30%; UM: 28% UF: 28%). Also, there was
      an increased frequency of anomalous Sylvian fissures on the left combined with
      multiple Heschl's gyri in either hemisphere in males with RTH (AM: 50%; AF: 9%;
      UM: 6%; UF: 0%). However, RTH subjects with anomalies did not have an increased
      frequency of ADHD as compared with RTH subjects with no anomalies. CONCLUSIONS:
      Abnormal thyroid hormone action in the male fetus early during brain development
      may be associated with grossly observable cerebral anomalies of the left
      hemisphere. The effects of mutations in the thyroid receptor beta gene provide a
      model system for studying the complex interaction of genetic and nongenetic
      factors on brain and behavioral development.

PMID- 7573178
TI  - Possible association between the dopamine D3 receptor gene and bipolar affective
      disorder.
AB  - A variety of studies have reported possible genetic associations between bipolar
      affective disorder and different loci using relative risk (case-control)
      comparisons. An alternative approach is to construct a contrast group using
      parental alleles which were not transmitted to an affected individual [Falk and
      Rubinstein, 1987: Ann Hum Genet 51:227-233]. We have used both approaches to test
      for possible associations between alleles of the dopamine D3 receptor gene and
      bipolar affective disorder. For relative risk studies, the probands of multiple
      incidence bipolar affective disorder families have been compared to alcoholic and
      psychiatrically normal contrast groups. Nontransmitted allele approaches have
      used bipolar affective disorder and alcoholic probands in which both parents were
      available for genotyping. Using the BalI restriction enzyme site polymorphism of
      Lannfelt et al. [1992: Psychiatr Genet 2:249-256], we have found no differences
      in the allele or genotype frequencies for bipolar vs. alcoholic or
      psychiatrically normal controls. In contrast, we have found evidence for an
      increased frequency of allele 1 and allele 1 containing genotypes in transmitted
      alleles from bipolar families.

PMID- 7573180
TI  - Towards the finer mapping of facioscapulohumeral muscular dystrophy at 4q35:
      construction of a laser microdissection library.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder
      which has been mapped to the 4q35 region. In order to saturate this distal 4q
      region with DNA markers, a laser-based chromosomal microdissection and
      microcloning procedure was used to construct a genomic library from the distal
      20% of chromosome 4, derived from a single human metaphase spread. Of the 100
      microclones analyzed from this library, 94 clones contained inserts sized from 80
      800 bp, with an average size of 340 bp. Less than 20% of these clones hybridized
      to human repeat sequences. Seventy-two single-copy clones were further
      characterized by Southern blot hybridization against a DNA panel of somatic cell
      hybrids, containing various regions of chromosome 4. Forty-two clones mapped to
      chromosome 4, of which 8 clones mapped into the relevant 4q35 region. Twenty of
      these chromosome 4-specific clones were screened against "zoo-blots"; 11 clones,
      of which 3 mapped to 4q35, identified conserved sequences. This is the first
      report to describe the isolation of potential expressed sequences derived from
      the FSHD region. These chromosome region-specific microclones will be useful in
      the construction of the physical map of the region, the positional cloning of
      potential disease-associated genes, and the identification of additional
      polymorphic markers from within the distal 4q region.

PMID- 7573182
TI  - Clinical, cytogenetic, and molecular diagnosis of Angelman syndrome: estimated
      prevalence rate in a Danish county.

PMID- 7573181
TI  - Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of
      susceptibility genes.
AB  - Using a systematically ascertained sample of 57 families, each having 2 or more
      members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have
      carried out linkage studies of 520 loci, covering approximately 70% of the genome
      for susceptibility loci for schizophrenia. A two-stage strategy based on lod
      score thresholds from simulation studies of our sample identified regions for
      further exploration. In each region, a dense map of highly informative
      dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed
      using dominant, recessive, and "affected only" models and nonparametric sib pair
      identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses
      gave a P value = .0001, corresponding to a lod score approximately equal to 3.00.
      For 8p22-p21, the maximum two-point lod score occurred using the "affected only"
      recessive model (ZMAX = 2.35; theta M = theta F); allowing for a constant sex
      difference in recombination fractions found in reference pedigrees, ZMAX = 2.78
      (theta M/theta F = 3). For a second region, 3p26-p24, the maximum two-point lod
      score was 2.34 ("affected only" dominant model), and the affected sib-pair P
      value was .01. These two regions are worthy of further exploration as potential
      sites of susceptibility genes for schizophrenia.

PMID- 7573184
TI  - Urea kinetics and when to commence dialysis.
AB  - Blood urea and serum creatinine levels are important factors in deciding when to
      start dialysis. Recently, in the assessment of dialysis adequacy, emphasis has
      shifted from reliance on these parameters to use of kinetic methods. We therefore
      applied urea kinetic modelling (UKM) to 63 consecutive chronic renal failure
      (CRF) patients at the time dialysis commenced and compared the results to those
      obtained after 6 months of dialysis treatment. Mean normalised urea clearance
      (daily KT/V) at the commencement of dialysis (KTi/V) was 0.15 +/- 0.05, a level
      indicative of underdialysis in regularly dialysed patients. After 6 months, mean
      daily KT/V was 0.35 +/- 0.12 in patients subsequently established on CAPD, and
      0.49 +/- 0.08 in those subsequently haemodialysed (both p < 0.001 compared to
      mean KTi/V). Serum creatinine levels on commencing dialysis were similar to those
      after 6 months treatment by either mode. Mean age (p < 0.01) and co-morbidity
      index (p < 0.05) were higher, and mean KTi/V lower (p < 0.05) in the 6 patients
      who died during a mean follow-up period of 10 +/- 4.5 months than in survivors.
      Hospitalisation rates during follow-up (excluding admissions for access surgery
      and training) correlated with age (r = 0.332, p < 0.01), co-morbidity index (r =
      0.351, p < 0.01) and KTi/V (r = -0.302, p < 0.05). Blood urea and serum
      creatinine levels on commencing dialysis were the same in those who died and in
      survivors and did not correlate with hospitalisation rates. Diabetics started
      dialysis with a similar mean KTi/V to non-diabetics but with a lower mean serum
      creatinine (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573183
TI  - Comparison of simultaneous renal clearances of true endogenous creatinine and
      subcutaneously administered iothalamate in man.
AB  - 125I-iothalamate and true endogenous creatinine clearances, measured over two
      short collections periods of 1 and 2 h, were compared simultaneously in 70
      patients with a variety of renal diseases and a wide range of renal function.
      Reproducibility of the iothalamate clearance was 18.5% and that of the creatinine
      clearance 12.2%. The slope of the regression was not significantly different from
      1 (95% confidence interval, CI, 0.964-1.155) for the whole group, nor in any
      subgroup chosen. The intercept at 12.6 ml/min (CI = 5.0-20.2) indicates that
      there is some creatinine secretion, but this was constant at all levels of GFR.
      It is concluded that although the clearance of true creatinine obtained during
      short collection periods consistently overestimates GFR by a constant proportion,
      it is a reproducible and accurate measure of GFR suitable for use in the clinical
      setting.

PMID- 7573185
TI  - Serum soluble HLA class I antigen levels in hemodialysis patients and following
      renal transplantation.
AB  - We measured the serum levels of soluble HLA class I antigen (sHLA-I) to evaluate
      the immune status of uremia and following renal transplantation. Twenty-one
      hemodialysis (HD) patients had serum samples collected for sHLA-I analysis before
      and after HD and also during the initial posttransplant period. The serum sHLA-I
      levels in patients undergoing HD were higher than in the normal controls (574.8
      +/- 431.1 vs. 415.6 +/- 256.1 ng/ml, p < 0.05). In the HD patients, HD duration
      was not correlated with serum sHLA-I levels (r = 0.01, p > 0.05), and pre- and
      post-HD serum sHLA-I levels were not significantly different (574.8 +/- 431.1 vs.
      568.3 +/- 398.4 ng/ml, p > 0.05). After successful renal transplantation, the
      serum sHLA-I levels decreased significantly (574.8 +/- 431.1 vs. 226.7 +/- 202.8
      ng/ml, p = 0.0001) but increased significantly during the rejection period as
      compared to the prerejection period (642.8 +/- 296.1 vs. 305.5 +/- 194.7 ng/ml, p
      = 0.0002). In conclusion, sHLA-I levels are stable in uremic status and can be
      used as a parameter for monitoring acute graft rejection in renal
      transplantation.

PMID- 7573187
TI  - Effects of prostaglandin E2 on mesangial cell migration.
AB  - Mesangial cell migration is a feature of certain renal diseases such as
      mesangiocapillary glomerulonephritis, a disorder which responds to treatment with
      cyclo-oxygenase inhibitors. We undertook the present study to determine whether
      prostaglandin E2 (PGE2) might have a direct effect on mesangial cell migration.
      PGE2 (10(-8) M) treated cells migrated a mean percent area of 16.8 +/- 0.5 during
      24 h when compared to control cells which migrated only a mean percent area of
      10.3 +/- 0.8 (p < 0.001). At 48 h, PGE2-treated cells migrated a mean percent
      area of 21.7 +/- 1.1 when compared to control cells which migrated only a mean
      percent area of 14.7 +/- 1.4 (p < 0.01). Meclofenamate (10(-5) M), a cyclo
      oxygenase inhibitor, significantly (p < 0.02) inhibited migration of mesangial
      cells (at 48 h controls 13.4 +/- 0.5 vs. meclofenamate-treated cells 3.2 +/-
      0.8). Since meclofenamate attenuates basal production of PGE2 by mesangial cells,
      inhibition of migration by mesangial cells by meclofenamate indicates that the
      basal production of PGE2 by mesangial cells also significantly contributes to the
      migration of mesangial cells. 3-Isobutyl-1-methylxanthine (IBMX, 10(-3) M), a
      phosphodiesterase inhibitor, also significantly (p < 0.001) enhanced migration of
      mesangial cells (controls 13.4 +/- 0.5 vs. IBMX-treated cells 20.8 +/- 0.5).
      These results suggest that mesangial cell migration is directly enhanced by PGE2.
      The present study provides a rationale for the use of cyclo-oxygenase therapy in
      patients with mesangiocapillary glomerulonephritis.

PMID- 7573188
TI  - Lipofuscin products, lipid peroxides and aluminum accumulation in red blood cells
      of hemodialyzed patients.
AB  - This study examines whether there is a relationship between aluminum overload and
      the accumulation of lipofuscin products (aging pigments) and lipid peroxides in
      red blood cells (RBC) of hemodialyzed patients. Lipid peroxides levels were
      assessed by the thiobarbituric acid reactivity; lipofuscin products were assessed
      by determining fluorescence in the lipid extracts at excitation 360 nm and
      emission 440 nm. Aluminum was measured by atomic absorption spectrophotometry.
      Controls were age-matched normal volunteers. Data show that there was a
      significant increase in the lipid peroxides and lipofuscin products in
      hemodialyzed patients compared with controls even after normalization with
      hemoglobin or phospholipids in RBC. Further, the increase in the lipid peroxides
      and lipofuscin products significantly correlated with the levels of aluminum
      accumulation in RBC of hemodialyzed patients. This study suggests that aluminum
      overload has a role in increased membrane peroxidation, which in turn can cause
      reduced RBC life span and contribute to anemia in chronic renal failure patients.

PMID- 7573189
TI  - Intraperitoneal recombinant human erythropoietin therapy: influence of the
      duration of continuous ambulatory peritoneal dialysis treatment and peritonitis.
AB  - This study was performed to investigate the factors that influence
      intraperitoneal absorption of recombinant human erythropoietin (rHuEPO) and to
      evaluate the differences of the pharmacokinetics of intraperitoneally
      administered rHuEPO before peritonitis and after recovery. First, the
      pharmacokinetics in different groups of continuous ambulatory peritoneal dialysis
      (CAPD) patients was studied. Thirty-six CAPD patients were enrolled and divided
      into four groups. Group 1 included 20 patients who were either just placed on
      CAPD therapy or had been on CAPD for < 1 year, but with a low frequency of
      peritonitis episodes. Group 1 was divided into four subgroups by body weight (20
      30, 31-45, 46-55, and > 55 kg). Group 2, patients who had received CAPD treatment
      for more than 1 year, was further divided into group 2a and group 2b according to
      a low or a high frequency of peritonitis episodes, respectively. rHuEPO (100
      U/kg) was administered as a single bolus of intravenous, subcutaneous, or
      intraperitoneal injection. Intraperitoneal rHuEPO was retained for 10 h. The
      results showed no significant differences between subcutaneous and
      intraperitoneal administration in group 1 patients. However, peak concentration,
      time to reach peak serum level, area under the curves, and bioavailability were
      substantially lower after intraperitoneal than after subcutaneous administration
      in group 2a and group 2b patients. There was no influence of body size on peak
      concentration and area under the curve in group 1 patients. Second, comparison of
      the pharmacokinetics of intraperitoneal administration before and after recovery
      from peritonitis in group 1 patients revealed that the serum levels of rHuEPO
      became lower after the occurrence of peritonitis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7573186
TI  - Carpal tunnel syndrome in patients undergoing CAPD: a collaborative study in 143
      centers.
AB  - Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who
      developed carpal tunnel syndrome (CTS) were retrospectively studied in 143
      centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and
      1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients
      treated solely with CAPD developed CTS 12-108 months after starting CAPD. The
      remaining 2 patients who were initially treated with HD for 7-9 years and then
      switched to CAPD developed this complication 9 years after starting CAPD. All 7
      patients were women, ranging in age from 32 to 70 (average 52) years. We detected
      the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in
      2 of 4 specimens from these patients. It was concluded that CAPD minimizes the
      emergence of CTS although constant surveillance is necessary to detect CTS in
      patients during CAPD.

PMID- 7573190
TI  - Association of post-renal transplant erythrocytosis and microalbuminuria:
      response to angiotensin-converting enzyme inhibition.
AB  - Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to
      be effective in the treatment of post-renal transplant erythrocytosis (PTE). In
      an attempt to assess the effect of drug treatment on serum erythropoietin level,
      glomerular filtration rate, and urinary protein excretion, we prospectively
      evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated
      with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean
      hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/-
      2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to
      respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia
      (HCT < 35%) while maintained on drug treatment. Although the mean serum
      erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/
      5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels
      was not identified. At the conclusion of the study, the serum erythropoietin
      levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and
      increased in the only patient with PTE who failed to respond to drug treatment.
      All patients tolerated the ACE inhibitor therapy without developing cough or
      hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances,
      and mean arterial blood pressures were unchanged throughout the study.
      Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g)
      developed in 5 patients with PTE and coincided with the onset of erythrocytosis
      (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE
      detection).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573191
TI  - High-output cardiac failure due to excessive shunting in a hemodialysis access
      fistula: an easily overlooked diagnosis.
AB  - A dialysis arteriovenous fistula caused life-threatening high-output cardiac
      failure in a 66-year-old patient. Excessive shunting through the dialysis fistula
      was demonstrated by invasive measurement of cardiac output, systemic arterial
      blood pressure, systemic vascular resistance, and oxygen consumption before and
      after temporary occlusion of the dialysis fistula. Noninvasive echocardiographic
      evaluation of the influence of fistula compression on cardiac output and
      noninvasive duplex measurement of the fistula flow also confirmed the diagnosis.
      Following surgical closure of the fistula, the patient's condition improved, and
      signs of congestive heart failure subsided. High-output cardiac failure is a rare
      complication of dialysis arteriovenous fistulas. The diagnosis may remain
      unrecognized for longer periods. Noninvasive methods for estimation of the
      hemodynamic importance of a fistula may be of help in the establishment of the
      proper diagnosis.

PMID- 7573192
TI  - Elimination of flucytosine by continuous hemofiltration.
AB  - Flucytosine is effective in the treatment of serious fungal infections. Some of
      the patients might have acute renal failure requiring continuous hemofiltration
      as renal replacement therapy. We evaluated the removal of flucytosine in a
      patient who received the drug for systemic Candida infection while undergoing
      continuous hemofiltration for acute renal failure. Arterial, venous, and
      ultrafiltrate sample pairs were collected to evaluate flucytosine removal.
      Ultrafiltrate/arterial drug concentration ratios and sieving coefficients
      obtained with the polysulfone membrane were higher than those obtained with the
      polyacrylonitrile membrane. Between 2.54 and 22.56 mg of flucytosine was removed
      from the patient per hour when the serum drug concentrations were 21.1-126.5
      mg/l. The amount of hemofiltration flucytosine removal was related to
      ultrafiltration flow rate, serum drug concentration, and hemofilter type. The
      mean continuous arteriovenous hemofiltration flucytosine clearance for the
      polysulfone membrane was 77.0 +/- (SD) 15.6% of the ultrafiltrate flow rate,
      while the clearance for the polyacrylonitrile membrane was 51.0 +/- (SD) 5.7%. In
      patients with renal failure, continuous hemofiltration can remove an appreciable
      quantity of flucytosine when the ultrafiltrate flow rate is high. Serum drug
      concentration determination is necessary to devise an optimal dosage regimen for
      the patient.

PMID- 7573193
TI  - Carotid-jugular arteriovenous fistula: a complication of temporary hemodialysis
      catheter.
AB  - The internal jugular vein is increasingly being used as a temporary route for
      dual-lumen hemodialysis catheter placement. It is thought to be safer than the
      subclavian or femoral vein sites. It is important, however, to point out that
      this route can also be associated with serious complications. Herein we describe
      a case of right common carotid artery fistula as a complication of the insertion
      of a polyurethane double-lumen hemodialysis catheter into the right internal
      jugular vein. A review of the literature on traumatic complications associated
      with central venous cannulation is also presented.

PMID- 7573194
TI  - Acute interstitial nephritis and uveitis with bone marrow granulomas and anti
      neutrophil cytoplasmic antibodies.
AB  - Acute interstitial nephritis (AIN) and uveitis of unknown etiology developed in a
      15-year-old girl. Symptoms and urinary abnormalities improved spontaneously but
      moderate renal dysfunction and anterior uveitis persisted. A repeat biopsy
      performed 2 years later showed focal tubulointerstitial changes, while bone
      marrow examination revealed granulomas. Simultaneously, antineutrophil
      cytoplasmic antibodies (ANCA) were detected, and decreases in T cell population
      and lymphocyte function were found. These immunological abnormalities normalized
      in parallel with clinical improvement with corticosteroid therapy, strongly
      suggesting that in some patients autoimmune disorders contribute to the
      pathogenesis of the disease.

PMID- 7573195
TI  - Remission of nephrotic syndrome of HBV-associated membranous glomerulopathy
      following treatment with interferon.
AB  - We report a 26-year-old homosexual man who developed membranous glomerulopathy
      with nephrotic syndrome secondary to hepatitis B virus infection and HBe
      antigenemia. Aminotransferase levels were minimally abnormal, and a liver biopsy
      showed mild chronic 'persistent' hepatitis. He was initially treated for 4 weeks
      with human lymphoblastoid alpha-interferon by subcutaneous injection without
      effect. A second 4-week course of interferon in combination with acyclovir also
      failed to eradicate HBeAg from the circulation or to reduce the proteinuria. Four
      years later, he developed new symptomatic hepatitis, with plasma
      aminotransferases elevated to 200-300 IU/l for more than 4 months. Treatment with
      interferon was again initiated, and by the 4th month of therapy, he had
      seroconverted to anti-e status, and cleared the HBeAg from circulation. At the
      same time, proteinuria significantly dropped from an average of 7 g/day to less
      than 0.5 g/day. Four years after completion of interferon treatment, he became
      HBsAg negative and anti-HBsAg reactive while remaining persistently HBeAg
      negative and anti-HBe positive. He has been free of edema, with normal renal and
      hepatic function, and his 24-hour protein excretion was less than 0.12 g/day.

PMID- 7573196
TI  - Peritoneal dialysis complicated by Bipolaris hawaiiensis peritonitis: successful
      therapy with catheter removal and oral itraconazol without the use of
      amphotericin-B.
AB  - Fungi classified in the genera Bipolaris are an uncommon source of infection in
      human diseases. It is also a rare source of peritonitis in peritoneal dialysis
      (PD) patients. All cases of Bipolaris peritonitis reported in the United States
      have occurred in the southern states. This form of peritonitis appears to have a
      good prognosis, with cure achieved only after removal of the peritoneal dialysis
      catheter and antifungal therapy. Systemic or intraperitoneal amphotericin-B with
      or without oral ketoconazole has been used in all previously reported cases.
      However, the role of antifungal therapy is unclear. We report a case of Bipolaris
      hawaiiensis peritonitis in a 73-year-old female on continuous cyclic peritoneal
      dialysis (CCPD) for 10 months who presented with a nonfunctioning peritoneal
      catheter. The catheter had characteristic dark gray particles, each composing a
      fungal ball within the lumen of the catheter. Microscopic examination confirmed
      the organism attached to the inner wall of the catheter. The patient achieved
      cure without using either amphotericin-B or ketoconazole. She was treated with
      removal of the catheter and a 2-week course of oral itraconazole 100 mg twice
      daily. A new catheter was placed after 1 month and the patient continued to do
      well on CCPD 12 months later with no evidence of recurrent infection. We conclude
      that (1) itraconazole can effect cure following removal of the catheter without
      using amphotericin-B or ketoconazole; (2) peritoneal dialysis can be safely
      reinstituted after itraconazole therapy for this uncommon fungal infection, and
      (3) itraconazole therapy allows for out-patient treatment of B. hawaiiensis
      peritonitis in peritoneal dialysis patients.

PMID- 7573197
TI  - Continuous ambulatory peritoneal dialysis complicated by Aureobasidium pullulans
      peritonitis.
AB  - We describe a case of peritonitis caused by Aureobasidium pullulans in a patient
      on continuous ambulatory peritoneal dialysis (CAPD). This dematiaceous fungus
      rarely causes infection in humans and to date has not been reported as an
      etiology of CAPD-associated peritonitis. The patient was managed successfully
      with peritoneal catheter removal and a prolonged course of intravenous
      amphotericin B, allowing resumption of CAPD. In vitro susceptibility testing
      confirmed sensitivity of this organism to amphotericin B.

PMID- 7573198
TI  - Endemic occurrence of glomerulonephritis associated with streptococcal impetigo.
AB  - We report here a case of type 1 mesangiocapillary glomerulonephritis as well as a
      case of mesangial proliferative glomerulonephritis associated with streptococcal
      skin infection superimposed on atopic dermatitis. Both were endemic occurrences
      of postinfectious glomerulonephritis developed after repeated dirty-skin
      treatments for atopic dermatitis performed by unauthorized individuals under
      unsanitary conditions. Of 20 patients who were similarly treated and subsequently
      admitted to our hospital because of skin infection and fever, 8 (40%) showed
      urinary abnormalities. Four patients had renal dysfunction with acute nephritic
      onset. Almost all showed a decrease in CH50 values and an increase in levels of
      antistreptolysin O and IgE. In the 2 cases presented here, the disease eventually
      regressed in association with improvement of the skin infection. Although the
      occurrence of postinfectious glomerulonephritis has recently become uncommon, we
      must take care to note urinary abnormalities as early as possible in order to
      prevent the progression of glomerulonephritis.

PMID- 7573200
TI  - Renal vein thrombosis in a severe form of renal disease.

PMID- 7573201
TI  - Beware of routine procedures.

PMID- 7573199
TI  - Nephrotic syndrome, malignant thymoma, and myasthenia gravis. Case report and
      review of the literature.
AB  - We describe a patient with nephrotic syndrome due to focal-segmental
      glomerulosclerosis, occurring 3 years after thymectomy and myasthenia gravis.
      Nine other cases of nephrotic syndrome associated with thymoma and myasthenia
      gravis reported in the literature are reviewed. The nephrotic syndrome may be due
      to T cell dysfunction associated with thymoma; however, animal models suggest
      that genetic factors may also be involved.

PMID- 7573202
TI  - Conscious sedation and the substance abuser.

PMID- 7573203
TI  - 'A soul in pain' revisited.

PMID- 7573204
TI  - Holding back the congressional budget axe.

PMID- 7573205
TI  - Do neonates feel pain?

PMID- 7573206
TI  - Relieving pain during ulcer healing.

PMID- 7573207
TI  - All about drugs. Adverse effects to watch for.

PMID- 7573208
TI  - Medication administration: how safe is your patient?

PMID- 7573209
TI  - Janus in the catbird seat: in defense of the editorial.

PMID- 7573210
TI  - Commonly asked questions about nutrition care.

PMID- 7573211
TI  - Bedside computers and confidentiality.

PMID- 7573212
TI  - For Joey's sake.

PMID- 7573213
TI  - A cautious look at heparin.

PMID- 7573215
TI  - Meeting the challenge of chest trauma.

PMID- 7573214
TI  - When your patient is in denial.

PMID- 7573218
TI  - Clinical snapshot: transient ischemic attack.

PMID- 7573219
TI  - How safe is your ED?

PMID- 7573217
TI  - Update on cardiovascular drugs and elders.

PMID- 7573220
TI  - Emergency! epiglottitis.

PMID- 7573221
TI  - Physician won't provide 'futile' care.

PMID- 7573216
TI  - 14 Tips for managing stress on the job.

PMID- 7573222
TI  - Is telephone triage calling you?

PMID- 7573224
TI  - Save a seat on the bus for me.

PMID- 7573223
TI  - Laying circles end to end.

PMID- 7573225
TI  - The battered woman.
AB  - There are battered women in every obstetrician-gynecologist's practice. A role
      for the physicians is to be an agent of change for the patient. This is
      accomplished by integrating questions related to woman battering in all primary
      care, obstetric, and gynecologic evaluations and by becoming informed about and
      referring to the resources for battered women in the community. An activist role
      in the community that encourages and supports zero tolerance for domestic
      violence will help stop this epidemic and crime.

PMID- 7573226
TI  - The relationship of birth weight and birth weight discordance to cerebral palsy
      or mental retardation later in life for twins weighing less than 2500 grams.
AB  - OBJECTIVE: This study tested the hypothesis that twins with a birth weight < 2500
      gm who subsequently had cerebral palsy or mental retardation had a birth weight
      distribution or birth weight discordance distribution differing from that of the
      total live-born twin population also weighing < 2500 gm at birth. STUDY DESIGN:
      All twins born in Sweden between 1973 and 1980 (n = 5382) and having a birth
      weight < 2500 gm were identified by using information stored at the Medical Birth
      Registry, the National Board of Health and Welfare, Stockholm, or at Statistics
      Sweden. To identify twins with cerebral palsy or mental retardation, a
      questionnaire bearing the personal identification number (given to all newborns
      in Sweden shortly after birth) was distributed to all rehabilitation centers, all
      county school boards, all local boards of education, and to all County Councils
      for the Provisions and Services for the Mentally Retarded. The questionnaire was
      distributed in 1988 and 1989 when the twins were > or = 8 years old. RESULTS:
      Altogether 115 disabled twins resulting from 99 pregnancies were identified. The
      incidence of disabled twins per 1000 was 21.4 (95% confidence interval 17.5 to
      25.2). No obvious difference was evident in the distribution of birth weight
      discordance when the twins with disability were compared with the population of
      all live-born twins having a birth weight < 2500 gm. Disabled twins had a
      significantly lower birth weight for gestational age (t = -3.5, p < 0.001), but
      in fact only 10 (8.7%) twins had a birth weight < -2 SD. No difference in the
      incidence of disability was found for twin A versus twin B (relative risk 1.3,
      95% confidence interval 0.8 to 1.9) or for like-sex versus unlike-sex twins
      (relative risk 1.0, 95% confidence interval 0.6 to 1.6). However, the larger twin
      in the pair had a significantly higher incidence of cerebral palsy than the
      smaller one did (relative risk 2.6, 95% confidence interval 1.4 to 4.8).
      CONCLUSIONS: Birth weight discordance for twins seems not to be related to
      disability later in life. The great majority of twins with a birth weight < 2500
      gm who later became disabled were appropriate for gestational age at birth.

PMID- 7573228
TI  - Hemodynamic and hormonal responses to atrial distension in the ovine fetus.
AB  - OBJECTIVE: Our purpose was to evaluate the hemodynamic and endocrine responses to
      elevations of atrial pressure in fetal sheep. STUDY DESIGN: By use of a
      randomized block design, 10 ovine fetuses underwent pulmonary artery constriction
      proximal to the ductus arteriosus with and without propranolol pretreatment.
      RESULTS: Atrial pressure doubled (p < 0.05), whereas mean arterial pressure
      remained unchanged (p > 0.05), in response to pulmonary artery constriction in
      both groups. Atrial natriuretic peptide tripled (p < 0.01), arginine vasopressin
      tripled (p < 0.05), and plasma renin activity doubled (p < 0.05) in both the
      constriction and constriction plus propranolol groups. No changes in fetal
      hematocrit values were demonstrated in any group. CONCLUSIONS: The fetal sheep
      responds to increased atrial pressure with not only increased levels of atrial
      natriuretic peptide but also with arginine vasopressin and plasma renin activity
      over time. These changes occur in spite of increases in both atrial pressure and
      atrial natriuretic peptide. We speculate that the fetal heart may participate in
      redistribution of cardiac output by releasing atrial natriuretic peptide and
      augmenting secretion of arginine vasopressin and plasma renin activity.

PMID- 7573227
TI  - Immunohistochemical characterization of placental nitric oxide synthase
      expression in preeclampsia.
AB  - OBJECTIVE: Our purpose was to compare the expression of endothelial nitric oxide
      synthase in the placenta and umbilical cord of preeclamptic placenta with that of
      the normotensive placenta. STUDY DESIGN: We compared placental endothelial nitric
      oxide synthase expression in preeclamptic (n = 3) with that in normal (n = 3)
      pregnancies. Frozen sections of umbilical cords, chorionic plate vessels, and
      terminal villi were immunostained with a monoclonal endothelial nitric oxide
      synthase antibody (H32). RESULTS: No difference in endothelial nitric oxide
      synthase immunostaining in the endothelium of the umbilical cord artery and vein,
      chorionic plate vessels, and stem villous vessels was found between preeclamptic
      and normotensive pregnancies. In contrast, in the preeclamptic placentas
      endothelial nitric oxide synthase immunostaining was seen in the small terminal
      villous vessels with underlying smooth muscle layer. In the syncytiotrophoblast
      endothelial nitric oxide synthase immunostaining appeared primarily apical in
      location and diffuse in distribution in the preeclamptic placentas but primarily
      basal and punctate in the normotensive placentas. CONCLUSIONS: Differences in
      endothelial nitric oxide synthase expression in terminal villous vessels and in
      syncytiotrophoblast may be a result of vascular alterations or damage that take
      place in the placenta in preeclampsia. These differences may alter the regulation
      of blood flow in the fetal and maternal placental vasculatures in preeclampsia.

PMID- 7573229
TI  - Inducible platelet adherence to human umbilical vein endothelium by
      anticardiolipin antibody-positive sera.
AB  - OBJECTIVE: Our purpose was to determine whether anticardiolipin antibody-positive
      sera alter platelet adherence to vascular endothelium by a platelet activating
      factor-dependent mechanism. STUDY DESIGN: Anticardiolipin antibody-positive sera
      were used in an in vitro platelet-endothelial adherence assay. Confluent
      endothelial monolayers were randomly assigned for exposure to a 20% concentration
      of experimental and control sera. Platelets were radiolabeled with chromium 51,
      and adherence was assessed by quantification of endothelium-associated gamma
      emission. RESULTS: Inducible platelet adherence was observed by endothelial cell
      preincubation with sera from anticardiolipin antibody-positive donors compared
      with anticardiolipin antibody-negative control experiments (n = 12, platelet
      adherence 6.4% +/- 1.3% vs 4.5% +/- 1.1%, respectively; p = 0.02). Compared with
      endothelial cell incubations alone, coincubation of platelets with
      anticardiolipin antibody-positive sera consistently augmented primary adherence
      (n = 6, p = 0.042). Furthermore, platelet-adherence induced by antibody-positive
      sera was consistently attenuated by specific platelet-activating factor
      antagonists in a dose-dependent fashion (p < 0.001) and was restored by
      exogenously administered platelet-activating factor. CONCLUSIONS: Anticardiolipin
      antibody-induced platelet adherence may constitute an important prerequisite for
      vascular thrombosis in antibody-positive patients. The findings from this in
      vitro model suggest direct involvement of platelet-activating factor in this
      process.

PMID- 7573230
TI  - Shear stress may stimulate release and action of nitric oxide in the human fetal
      placental vasculature.
AB  - OBJECTIVE: Our purpose was to determine the effect of perfusate flow or viscosity
      on release and action of nitric oxide in the human fetal-placental vasculature in
      vitro. STUDY DESIGN: Cotyledons from normal term placentas were perfused with
      Hanks' buffered saline solution gassed with 95% oxygen and 5% carbon dioxide, pH
      7.4, at 37 degrees C with a maternal flow rate of 10 ml/min. Fetal flow rate was
      varied from 1 to 10 ml/min at 10-minute intervals (n = 6), and perfusion pressure
      was recorded. Viscosity was varied by perfusion of both circulations with Hanks'
      balanced salt solution containing 0, 2.5, 5.0, 7.5, or 10% dextran, the
      concentration being changed every 20 minutes and pressure recorded at fetal flow
      rates of 4 (n = 4) or 1 ml/min (n = 7). All experiments were performed in the
      presence or absence of the nitric oxide synthase inhibitor N-nitro-L-arginine
      (10(-3) mol/L) in the same placentas. Data were analyzed by analysis of variance
      with repeated measures. RESULTS: Increasing fetal flow rate with or without N
      nitro-L-arginine resulted in a significant increase in perfusion pressure (p =
      0.0011). Addition of N-nitro-L-arginine gave an overall significant increase in
      perfusion pressure (p = 0.0048). At a fetal flow rate of 4 ml/min increasing
      dextran concentration with or without N-nitro-L-arginine gave a significant
      increase in perfusion pressure (p = 0.0011), but the increase in perfusion
      pressure in the presence of N-nitro-L-arginine did not reach significance (p =
      0.06). At 1 ml/min increasing dextran concentration resulted in a significant
      increase in fetal perfusion pressure (p = 0.001), but no significant effect of N
      nitro-L-arginine was observed. CONCLUSION: Altering shear stress by increasing
      fetal flow rate or viscosity of the medium may increase synthesis and release of
      nitric oxide, which attenuates increases in perfusion pressure.

PMID- 7573232
TI  - Thyrotropin-releasing hormone: does two hundred micrograms provide effective
      stimulation to the preterm fetal pituitary gland compared with four hundred
      micrograms?
AB  - OBJECTIVE: Our purpose was to compare the response of the fetal pituitary-thyroid
      axis to 200 and 400 micrograms of thyrotropin-releasing hormone administered to
      the mother immediately before delivery with a control group. STUDY DESIGN: A
      randomized controlled trial was conducted of 26 women at gestational ages between
      24 weeks and 33 weeks 6 days who had received one or more doses of betamethasone
      who were expected to be delivered within 1 to 4 hours. Women received either 200
      or 400 micrograms of thyrotropin-releasing hormone or were in the control group.
      RESULTS: Thyroid-stimulating hormone determinations on cord blood had a higher
      mean level in both treatment groups compared with the control group. No
      differences were seen in cord blood results between the two treatment groups for
      thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, free
      triiodothyronine, and prolactin levels. The only other differences found were in
      a higher level in total thyroxine and a lower level of free thyroxine in the 400
      micrograms thyrotropin-releasing hormone group compared with the 200 micrograms
      group in the 48-hour blood determinations. CONCLUSION: Both 200 and 400
      micrograms of thyrotropin-releasing hormone provided fetal pituitary stimulation,
      as reflected in fetal thyroid-stimulating hormone levels in cord blood, and both
      gave significantly higher levels compared with a control group.

PMID- 7573231
TI  - Nitric oxide concentrations are increased in the fetoplacental circulation in
      preeclampsia.
AB  - OBJECTIVE: The aim of this study was to measure serum concentrations of total
      nitrites, as an index of nitric oxide synthesis, in the maternal and fetal
      circulations of normal pregnancies and in pregnancies complicated by
      preeclampsia. STUDY DESIGN: We studied 32 women with preeclampsia and 36 with
      uncomplicated pregnancies. Maternal venous blood samples were collected from all
      of the patients, and umbilical venous blood was collected from 13 of the
      preeclamptic group and 17 of the control group. Serum nitric oxide concentrations
      were determined with the Greiss reaction by measuring combined oxidation products
      of nitric oxide, serum nitrite and nitrate after reduction with nitrate
      reductase. RESULTS: There were no significant differences in maternal serum
      nitrite concentrations between the groups (control group 29.8 +/- 1.07 mumol/L,
      preeclamptic group 29.5 +/- 1.06 mumol/L). Significantly higher serum nitrite
      concentrations were found in umbilical venous serum in the preeclamptic group
      compared with the control group (34.59 +/- 1.12 mumol/L vs 23.90 +/- 1.05
      mumol/L, p < 0.01). CONCLUSIONS: Total nitrites are increased in the
      fetoplacental circulation in preeclampsia. These results support the hypothesis
      that increased nitric oxide production may be a compensatory response to improve
      blood flow or may play a role in limiting platelet adhesion and aggregation.

PMID- 7573233
TI  - Placental histomorphometry and morphometric diffusing capacity of the villous
      membrane in pregnancies complicated by maternal iron-deficiency anemia.
AB  - OBJECTIVE: Our purpose was to determine the morphometric diffusing capacity of
      the human placental villous membrane in cases of maternal iron-deficiency anemia.
      STUDY DESIGN: Material from 10 term placentas from mothers with hemoglobin levels
      < 10 gm/100 cm3 was compared stereologically with control material from women
      with normal hemoglobin concentrations matched for age and parity. Data were
      compared with Student t test. RESULTS: Birth and placental weights were constant
      between the two groups. Maternal anemia was associated with a significant
      reduction in both volume and surface area of intermediate and terminal villi
      (157.8 vs 234.5 cm3 and 9.5 vs 14.9 m2, respectively). There was a concomitant
      rise in the volume of pathologic areas (32.1 vs 4.1 cm3). Harmonic mean thickness
      of the villous membrane was significantly less in the anemia cases (5.86 vs 7.15
      microns), because of an increase in volume fraction of the fetal capillaries.
      Consequently, the morphometric diffusing capacity of the villous membrane was
      maintained (4.49 vs 5.31 cm3.min-1.mm Hg-1, t = 1.04, p > 0.05). CONCLUSIONS:
      There is a reduction rather than an enlargement of the placental villous tree in
      cases of maternal anemia. This may be because of underlying malnutrition.
      Nonetheless, the placenta adapts through thinning of the villous membrane so that
      diffusing capacity is maintained at normal levels.

PMID- 7573234
TI  - Single umbilical artery: does it matter which artery is missing?
AB  - OBJECTIVE: Our purpose was to determine whether the presence of congenital
      anomalies in fetuses with a single umbilical artery is related to the side of the
      missing artery. STUDY DESIGN: During an 18-month prospective study, the side of
      the missing artery was identified in all pregnancies with a single umbilical
      artery (n = 77). Targeted sonograms and perinatal follow-up were obtained.
      RESULTS: The left umbilical artery was absent in 56 of 77 (73%) fetuses, compared
      with 21 of 77 (27%) for the right artery, p < 0.0001. Congenital anomalies
      occurred in 20 of 77 (26%) fetuses, with 16 of 56 (29%) in those with absence of
      the left artery and 4 of 21 (19%) in those with absence of the right artery, p =
      0.561. Complex congenital anomalies occurred in 9 of 20 (45%) fetuses. All
      complex anomalies had absence of the left artery, p = 0.103. Cytogenetic
      abnormalities were noted in 6 fetuses, all with absence of the left artery, p =
      0.181. In fetuses with a single umbilical artery as an isolated finding, small
      for-gestational-age fetuses occurred in 4 of 50 (8%) pregnancies. CONCLUSION: In
      fetuses with a single umbilical artery the left artery is more commonly absent
      than the right artery. In our series cytogenetic and complex fetal anomalies
      occurred exclusively in fetuses with absence of the left artery. In contrast to
      previous reports, the incidence of small-for-gestational-age fetuses does not
      appear to be increased in cases of an isolated single umbilical artery.

PMID- 7573235
TI  - A chloride channel from human placenta reconstituted into giant liposomes.
AB  - OBJECTIVE: Ion channels play important roles in epithelial transport, but they
      are difficult to access for conventional electrophysiologic studies in intact
      placenta. The purpose of this work was to explore the suitability of purified
      trophoblast plasma membrane as a source of ion channels for reconstitution in
      artificial lipid membranes. STUDY DESIGN: Human placental brush border membranes
      were purified by differential and gradient centrifugation and fused with small
      liposomes. Giant liposomes were then generated by a cycle of dehydration and
      rehydration. These giant liposomes are suitable for electrophysiologic studies
      and were probed for the presence of active ion channels by the patch-clamp
      method. RESULTS: The results reported here indicate the presence of a high
      conductance chloride channel showing some similarities with "maxi" chloride
      channels described in secreting and absorbing epithelia. The channel had a slight
      outward rectification with conductances of 232 and 300 pS at negative and
      positive potentials, respectively. CONCLUSIONS: For the first time successful
      reconstitution of a human placental ion channel is achieved in a system suited
      for electrophysiologic studies. The chloride channel described might play a role
      in transplacental transport.

PMID- 7573236
TI  - Expression of parathyroid hormone-related peptide and its receptor messenger
      ribonucleic acid in human amnion and chorion-decidua: implications for secretion
      and function.
AB  - OBJECTIVE: Our purpose was to define the location and packaging of parathyroid
      hormone-related peptide in amnion-chorion and the potential target tissues for
      its action in fetal membranes. STUDY DESIGN: We studied fetal membranes by use of
      light microscopic immunocytochemistry with three monoclonal antibodies against
      distinct regions of the parathyroid hormone-related peptide molecule. For
      electron microscopy immunogold analysis with a monoclonal antibody specific to
      the 109-141 fragment was used to observe parathyroid hormone-related peptide
      intracellularly in amnion membrane and in the chorion layers. Multiplex reverse
      transcriptase-polymerase chain reaction with Southern blotting was used to
      identify parathyroid hormone/parathyroid hormone-related peptide receptor and
      control messenger ribonucleic acids in amnion and chorion-decidua. RESULTS: All
      monoclonal antibodies revealed immunoreactive parathyroid hormone-related peptide
      in the amniotic epithelial cells and in some fibroblast-like cells embedded in
      the extracellular matrix of the amnion. Parathyroid hormone-related peptide was
      also found in the chorion in fibroblast and trophoblast layers and in decidua.
      Ultrastructurally immunogold particles were evenly distributed throughout the
      amniotic epithelial cells and were present in apical microvilli and near the
      basal membranes. Electron microscopy studies of the chorion cytotrophoblast also
      showed freely dispersed immunogold particles of parathyroid hormone-related
      peptide with no packaging in secretory granules. Low to undetectable levels of
      parathyroid hormone/parathyroid hormone-related peptide receptor messenger
      ribonucleic acid were found in amnion tissue, whereas abundant receptor messenger
      ribonucleic acid was found in chorion-decidua. CONCLUSIONS: These results suggest
      the presence of a parathyroid hormone-related peptide paracrine system within the
      human fetal membranes.

PMID- 7573237
TI  - An animal model for hemolytic disease of the fetus and newborn. II. Fetal effects
      in New Zealand rabbits.
AB  - OBJECTIVE: The addition of ultrasonography and ultrasonographically directed
      fetal blood sampling was attempted in an effort to study the fetal effects of red
      blood cell alloimmunization in a rabbit model. STUDY DESIGN: Nineteen New Zealand
      does were alloimmunized to incompatible red blood cells. Sensitized does were
      bred twice, once with a homozygous buck of incompatible blood type and once with
      a homozygous buck of compatible blood type. Ultrasonographic examinations were
      performed on days 20 and 27 of gestation (term 28 to 31 days). Fetal blood
      sampling was undertaken on day 27 of gestation, and hematologic data were
      compared between compatible and incompatible litters. RESULTS: A total of 41
      pregnancies occurred in 19 does. Fetal hemoglobin was higher in the compatible
      litters (9.7 gm/dl vs 5.8 gm/dl, p < 0.001), whereas no difference could be
      detected between the respective reticulocyte counts (31.9 vs 36.0/100 red blood
      cells, p = 0.2). Hydrops fetalis was noted in none of 18 compatible litters
      versus 12 of 19 incompatible litters (p < 0.01). CONCLUSION: A disease analogous
      to human hemolytic disease of the newborn can be induced in the rabbit fetus.

PMID- 7573238
TI  - Vascular endothelial growth factor gene expression in ovine placenta and fetal
      membranes.
AB  - OBJECTIVE: The purpose of this study was to explore the gene expression of
      vascular endothelial growth factor (VEGF) in placental cotyledon, chorion, and
      amnion of the ovine fetus. STUDY DESIGN: Time-dated pregnant sheep with singleton
      or twin fetuses at a gestational age ranging from 100 to 140 days were used for
      the study. Placental cotyledonary, chorionic, and amniotic tissues were collected
      and processed for messenger ribonucleic acid analysis by Northern blotting and
      reverse transcription-polymerase chain reaction. RESULTS: By use of a phosphorus
      32-labeled human VEGF complementary deoxyribonucleic acid probe, a prominent VEGF
      messenger ribonucleic acid transcript of 3.7 kb was detected in the cotyledon,
      chorion, and amnion. A minor band of 1.7 kb was also found but only in the
      cotyledon and chorion. The abundance of messenger ribonucleic acid encoding VEGF
      was highest (p < 0.001) in the cotyledon and lowest in the amnion. In these
      tissues polymerase chain reaction-amplified products corresponding to VEGF121,
      VEGF165, VEGF189, and VEGF206 were identified by ethidium bromide. In addition, a
      polymerase chain reaction fragment corresponding to VEGF145 was observed. These
      fragments produced specific hybridization signals with the human VEGF radioactive
      probe where the intensity of the signal was strongest for VEGF165 and weakest for
      VEGF189. CONCLUSIONS: VEGF gene expression was detected in the cotyledon,
      chorion, and amnion of the near-term ovine fetus. These findings suggest that
      vascular endothelial growth factor may play a role in the induction of
      angiogenesis and promotion of permeability in the microvessels that perfuse the
      placental and fetal membranes.

PMID- 7573239
TI  - Transport of immunoglobulin G and its subclasses across the in vitro-perfused
      human placenta.
AB  - OBJECTIVE: The transport of immunoglobulin G and its subclasses 1 to 4 was
      investigated in the in vitro-perfused isolated cotyledon of the human placenta.
      STUDY DESIGN: An in vitro system with separate perfusion of the villous capillary
      system (fetal compartment) and the corresponding intervillous space (maternal
      compartment) was set up in an isolated cotyledon of human term placenta. After a
      2-hour control phase with both compartments perfused in a closed circuit with
      NCTC-135 tissue culture medium together with Earl's balanced salt solution (2:1),
      media were exchanged in both circuits and for the experimental phase
      immunoglobulin G (Sandoglobulin) together with carbon 14-labeled bovine serum
      albumin (5-10 microCi) was added to the maternal compartment at a concentration
      of 6 gm/L. During the experimental phase, lasting between 2 and 5 hours, samples
      were taken from the maternal and fetal compartments every 30 minutes up to 2
      hours and every 60 minutes thereafter. RESULTS: During the control phase
      immunoglobulin G appeared in the maternal perfusate and reached a plateau at 60
      to 80 mg/L, whereas the concentration in the fetal perfusate did not exceed 20
      mg/L. A similar pattern of release was observed for hemoglobin, suggesting a
      washout of remains of blood from the intervillous space and the villous vascular
      compartment. After addition of immunoglobulin G to the maternal circuit during
      the first 2 hours in three of four experiments, no change in immunoglobulin G
      concentration was seen in the fetal circuit, and only in the fourth and fifth
      hours did the fetal concentration increase to 0.6% of the maternal concentration.
      In contrast, carbon 14-labeled bovine serum albumin was already detectable in the
      fetal circuit after 1 hour, but the level remained constant at 0.1% of the
      maternal concentration. Total immunoglobulin G transfer was estimated at 0.5% of
      the amount added to the maternal circulation, which was five times higher than
      total transfer of bovine serum albumin. Transfer was shown for all four
      subclasses. At the end of the experiment the ratio of immunoglobulin G1 to
      immunoglobulin G2 in the fetal perfusate was significantly higher than in the
      maternal perfusate (3.8 vs 1.8), suggesting preferential transfer of
      immunoglobulin G1. CONCLUSION: Transfer of all four immunoglobulin G subclasses
      of a commercially available immunoglobulin G preparation across the human
      placenta from the maternal to the fetal side was demonstrated by the dual in
      vitro perfusion system. There is a preferential transfer for immunoglobulin G1.

PMID- 7573240
TI  - Nuchal cords: timing of prenatal diagnosis and duration.
AB  - Nuchal cords can be diagnosed prenatally with ultrasonographic imaging. A
      prospective study determined the timing of nuchal cord formation and, in some
      cases, resolution before delivery.

PMID- 7573241
TI  - Excision of ovarian dermoid cyst by laparoscopy and by laparotomy.
AB  - OBJECTIVES: Our purpose was to evaluate the efficacy of laparoscopic ovarian
      dermoid cystectomy and to compare the operative course, postoperative course, and
      complications between the laparoscopy and the laparotomy techniques. STUDY
      DESIGN: The safety and efficacy of laparoscopic ovarian dermoid cystectomy were
      evaluated in 40 women. Twenty-nine of 40 patients underwent laparoscopic excision
      of a solitary dermoid cyst without any additional procedure. The operative
      course, the postoperative course, and complications among these 29 women were
      compared with those of 26 other women who underwent a similar procedure by
      laparotomy. RESULTS: Spillage of the cyst's content did not lead to any
      complication. The operating time in the laparoscopy group was 73.5 +/- 4.7
      minutes and in the laparotomy group it was 41.4 +/- 2.9 minutes. The duration of
      hospitalization was significantly shorter in the laparoscopy group (0.7 +/- 0.2
      days) than in the laparotomy group (3.8 +/- 0.1 days). CONCLUSIONS: Although
      ovarian dermoid cystectomy by laparoscopy is associated with a longer operating
      time than by laparotomy, the duration of hospitalization is shorter and recovery
      is faster. Spillage of the contents of the dermoid cyst does not lead to any
      complication; perhaps this is due to the liberal irrigation of the peritoneal
      cavity.

PMID- 7573243
TI  - The effect of diagnosis and treatment delay on prognostic factors and survival in
      endometrial carcinoma.
AB  - OBJECTIVE: The aim of this study was to assess the association of diagnosis and
      treatment delay with established prognostic factors and survival. STUDY DESIGN:
      The study group comprised 181 consecutive patients with endometrial carcinoma
      diagnosed between 1970 and 1986, whose records contained details with regard to
      diagnosis delay; 174 of them also contained details with regard to treatment
      delay. RESULTS: The significant prognostic factors that we found, namely, age,
      clinical stage, grade, depth of myometrial invasion, and histologic type, are in
      line with those of other studies. However, no significant correlation was found
      between the duration of delay and these prognostic factors or with survival.
      CONCLUSION: We conclude that delay of diagnosis (< 1 year) and of treatment of <
      4 months do not compromise survival of patients with endometrial cancer.

PMID- 7573242
TI  - The effect of topical 20% benzocaine on pain during loop electrosurgical excision
      of the cervix.
AB  - OBJECTIVE: Our purpose was to evaluate the effect of cervical application of 20%
      benzocaine on the pain associated with subsequent cervical injection of local
      anesthetic and tissue excision during the loop electrosurgical excision procedure
      of the cervix. STUDY DESIGN: Fifty consecutive women scheduled for loop
      electrosurgical excision were randomized by use of computer-generated numbers to
      receive cervical application of either 20% benzocaine or placebo gel in a double
      blinded fashion. A visual analog scale was used to measure the pain associated
      with both cervical injection of local anesthetic and tissue excision. RESULTS:
      Lower mean pain scores were associated with the use of benzocaine gel for both
      anesthetic injection and tissue excision, but these scores did not reach
      statistical significance in either group. CONCLUSION: Preoperative cervical
      application of 20% benzocaine does not appear to reduce the pain associated with
      either subsequent local anesthetic injection or tissue excision during the loop
      electrosurgical excision procedure of the cervix.

PMID- 7573244
TI  - Onapristone (ZK 98.299): a potential antiprogestin for endometrial contraception.
AB  - OBJECTIVES: The effects of the antiprogestin onapristone (ZK 98.299) on
      fertility; menstrual cycle length; duration of menses; serum estradiol,
      progesterone, and cortisol concentrations; and endometrial morphologic features
      were studied in adult bonnet monkeys. STUDY DESIGN: Five animals were treated
      subcutaneously with the vehicle and another nine with either 2.5 (n = 4) or 5 mg
      of onapristone per animal (n = 5). Treatment was initiated on day 5 of the first
      treatment cycle, and thereafter onapristone was administered every third day for
      four to seven consecutive cycles. The females were placed with adult males during
      the periovulatory period, which was assessed by frequent analysis of serum
      estradiol concentrations. In the final treatment cycle an endometrial biopsy was
      performed on day 8 after a midcycle estradiol peak in the ovulatory cycle, or
      around day 20 if the cycle was anovulatory. Blood samples for estradiol,
      progesterone, and cortisol measurement were collected every third day, except for
      the periovulatory period when sampling was more frequent. RESULTS: Each of the
      five animals treated with the vehicle became pregnant: one in the first, three in
      the second, and one in the third mated cycle, whereas only one of nine treated
      with onapristone became pregnant. Four animals treated with 2.5 mg of onapristone
      for 17 cycles and another four treated with a 5 mg dose for 21 cycles did not
      conceive. In eight animals that did not conceive the first three treatment cycles
      of six were ovulatory, and in the remaining two animals two cycles of each were
      ovulatory. During treatment the mean menstrual cycle length was not altered
      significantly; however, in one it was shortened and in another two it was
      prolonged. Similarly, the mean duration of menses was not significantly affected,
      but in some cycles it was reduced. Moreover, there was only slight bleeding in
      some treatment cycles. Ovulation occurred in 30 of 45 treatment cycles, including
      the final treatment cycle during which the biopsy was taken, as indicated by
      serum estradiol and progesterone concentrations. In some of the ovulatory cycles
      prolonged treatment suppressed luteal activity; however, in the ovulatory cycles
      the duration of follicular and luteal phases was not significantly affected. In
      the anovulatory cycles there was a delayed increase in serum estradiol
      concentrations, suggesting a partial inhibition of folliculogenesis. In treated
      animals endometrial growth and development was retarded and rendered out of
      phase. In animals treated with the higher (5 mg) onapristone does the endometrial
      glands had partially regressed, the secretory activity was blocked, and stromal
      compaction was evident. The treatment had no significant effect on serum cortisol
      levels. CONCLUSIONS: This study demonstrates that low-dose onapristone treatment
      throughout the menstrual cycle prevents pregnancy without disturbing the
      menstrual cycle and ovulation in the majority of cycles. However, anovulation and
      luteal insufficiency occurred in some animals during prolonged treatment. The
      contraceptive effect in the ovulatory cycles seems primarily related to the
      retardation of endometrial development resulting in the inhibition of endometrial
      receptivity. It appears likely that a dose or treatment regimen of onapristone
      that will inhibit endometrial receptivity and prevent implantation without
      affecting the menstrual cycle even on prolonged treatment could be identified.

PMID- 7573247
TI  - The regulation of plasminogen activators and plasminogen activator inhibitor type
      1 in endothelial cells by sex hormones.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of 17 beta
      estradiol, progesterone, and testosterone on secretion of plasminogen activators
      and plasminogen activator inhibitor type 1 by cultured endothelial cells. STUDY
      DESIGN: Bovine aortic endothelial cells were cultured in medium that contained 17
      beta-estradiol, progesterone, or testosterone at various concentrations (10(-13)
      to 10(-6) mol/L). Plasminogen activator activity in culture medium in the
      presence of cells was assayed after a 36-hour incubation using chromogenic
      substrate and iodine 125-labeled fibrin plate assays. Plasminogen activator
      inhibitor type 1 antigen was detected in conditioned media of bovine aortic
      endothelial cells by Western blotting analysis. RESULTS: All three steroid
      hormones exhibited biphasic dose-response effects, characterized by stimulation
      of plasminogen activator secretion at lower concentrations and inhibition of
      plasminogen activator secretion at higher concentrations. A significant
      stimulatory effect on plasminogen activator secretion (74% over control) was
      observed at a 17 beta-estradiol concentration of 10(-12) mol/L (p < 0.03). At
      higher concentrations of 17 beta-estradiol, progesterone, and testosterone,
      inhibition of plasminogen activator secretion was observed (p < 0.05). Decreased
      levels of plasminogen activator inhibitor type 1 antigen were detected in
      supernatants treated with either 17 beta-estradiol or progesterone at a
      concentration of 10(-12) mol/L and were maximal at 10(-7) mol/L 17 beta
      estradiol, progesterone, and testosterone. CONCLUSION: The secretion of
      plasminogen activators and plasminogen activator inhibitor type 1 is regulated in
      a biphasic dose-dependent manner by sex hormones in bovine aortic endothelial
      cells.

PMID- 7573246
TI  - Patterns of luteinizing and follicle-stimulating hormone pulsatility in
      menopausal women: correlation with plasma testosterone level and vasomotor
      instability episodes.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that subtle
      differences among postmenopausal women can be detected by careful analysis of
      plasma luteinizing hormone and follicle-stimulating hormone pulses. STUDY DESIGN:
      Twelve postmenopausal women not receiving estrogen therapy were admitted for
      continuous blood withdrawal at the rate of 1 ml/min. Aliquots of 3 ml of pooled
      blood were collected every 3 minutes for 3 hours for the measurement of plasma
      luteinizing hormone and follicle-stimulating hormone. Estradiol, estrone, free
      testosterone, androstenedione, and dihydrotestosterone were measured from pooled
      specimens. Concomitantly, continuous recordings of peripheral blood flow and
      peripheral temperature from the opposite arm were obtained to detect vasomotor
      instability episodes. RESULTS: Analysis of gonadotropin pulses revealed a single
      pattern of plasma follicle-stimulating hormone but two distinct patterns of
      luteinizing hormone frequency and amplitude. One group of six women had a low
      mean (+/- SEM) interpulse interval frequency of 0.8 +/- 0.26 (p < 0.005) and a
      high mean amplitude of 18.4 +/- 1.8 IU/L (p < 0.05). The second group of six
      women had a high mean interpulse interval frequency of 3.5 +/- 0.34 and a low
      mean amplitude of 12.2 +/- 1.8 IU/L luteinizing hormone pulses. Women with this
      pattern had more inter-vasomotor instability episode intervals (3.5 +/- 1.6) than
      did women with low frequency and high amplitude (1.3 +/- 0.5, p < 0.001). Women
      with low frequency and high amplitude pulses had higher plasma levels of estrone
      (266 +/- 33 nmol/L), testosterone (2.3 +/- 0.7 mmol/L), and free testosterone
      (8.0 +/- 0.1 pmol/L, p < 0.05). CONCLUSION: There are subgroups of postmenopausal
      women with different patterns of luteinizing hormone pulsatility. This difference
      can be explained by higher steroid levels in women with low frequency and high
      amplitude pulses.

PMID- 7573245
TI  - Case-control study of risk factors for partial molar pregnancy.
AB  - OBJECTIVE: The purpose of our study was to identify risk factors for partial
      molar pregnancy from a woman's general, reproductive, and dietary history. STUDY
      DESIGN: Sixty-five women with pathologically confirmed partial molar pregnancy
      were interviewed, and their experiences were compared with those of 130 age
      matched control women who had successfully completed a pregnancy with delivery of
      a live infant at the same hospital during the same calendar period. RESULTS:
      Multivariate analysis revealed that exposures which independently and
      significantly predicted increased risk for partial molar pregnancy included
      irregular cycles, pregnancy histories including only male infants among prior
      live births, and oral contraceptive use for > 4 years. Dietary factors previously
      postulated for complete molar pregnancy including protein, fat, vitamin A, or
      carotene were found not to be related to risk for partial molar pregnancy.
      CONCLUSION: Epidemiologic patterns for complete and partial molar pregnancies
      appear to differ somewhat; risk for partial mole is associated with reproductive
      history but not dietary factors.

PMID- 7573248
TI  - Immunohistochemical analysis of alpha 1-integrins in cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to determine and compare the expression
      of the alpha 2-, alpha 3-, alpha 4- and alpha 5-subunits of the beta 1-family of
      integrins in both the normal and the carcinomatous cervix. STUDY DESIGN: A total
      of 22 solid tissue specimens (18 cancer and 4 normal) were analyzed
      immunohistochemically. The double-stain technique used an avidin-biotin complex
      kit to identify the various integrins and alkaline phosphatase-anti-alkaline
      phosphatase kit to identify the epithelial cells. Staining intensity, the main
      outcome measured, was graded as absent, weak, moderate, or strong. Statistical
      analysis was performed with the Wilcoxon rank sum test for nonparametric data.
      RESULTS: The alpha 2- and alpha 3-integrins stained the normal cervix epithelium
      more intensely than the stroma (p = 0.03). The alpha 4- and alpha 5-integrins
      stained both the stroma and the normal epithelium similarly. The alpha 2-integrin
      was absent in the stroma of all 18 cancer specimens despite being present in the
      epithelial regions of 14 to 18 cancers. The alpha 3-integrin had a greater
      staining intensity in the stroma of the cancers than in the epithelial regions (p
      = 0.002). Both alpha 4- and alpha 5-integrins were absent in the epithelial
      regions of the cancers but present in the stroma. CONCLUSIONS: The distribution
      and intensity of integrin expression in cervical cancer differ from their
      expression in the normal cervix. In particular, the fibronectin receptors, alpha
      4 and alpha 5, were absent in the epithelial regions of the cervical cancers, and
      alpha 3 also had diminished expression in the malignant epithelium. These changes
      correlate well with the changes expected in malignant transformation.

PMID- 7573249
TI  - Growth hormone receptor messenger ribonucleic acid expression in leiomyoma and
      surrounding myometrium.
AB  - OBJECTIVE: Uterine leiomyomas are the most common pelvic tumors, occurring in one
      of four women, and they represent the single most common indication for
      hysterectomy. The genesis and growth-promoting factors responsible for their
      development are poorly understood. We speculate that growth hormone may play a
      role in the initiation of these tumors; women with acromegaly have a higher
      incidence of leiomyomas and growth hormone promotes uterine growth in rats, with
      or without the addition of estradiol. We evaluated the presence of growth hormone
      receptor messenger ribonucleic acid in the human uterus and leiomyomas to
      investigate whether growth hormone might act directly rather than by hepatic
      generation of insulin-like growth factor-I. STUDY DESIGN: Paired samples of
      leiomyomas and adjacent normal myometrium from nine premenopausal women (32 to 52
      years old) were collected at surgery. Three patients received a gonadotropin
      releasing hormone agonist for 3 months before the surgical procedure; six did not
      receive any adjuvant therapy. We used a digoxigenin-labeled oligoprobe sharing no
      homology to the growth hormone-binding protein or to the prolactin receptor, to
      investigate whether growth hormone receptor messenger ribonucleic acid was
      present in tissue sections or amplified complementary deoxyribonucleic acid from
      leiomyoma and the surrounding myometrium. RESULTS: The ratios of growth hormone
      receptor/reduced glyceraldehyde-phosphate dehydrogenase in leiomyomas and the
      surrounding myometrium as assessed by densitometry analysis of polymerase chain
      reaction products were similar and were not altered by gonadotropin-releasing
      hormone agonist treatment. In situ hybridization localized the growth hormone
      receptor messenger ribonucleic acid to the nuclei and cytoplasm of leiomyoma and
      myometrium. CONCLUSION: The presence of growth hormone receptor messenger
      ribonucleic acid suggests that the human uterus is a target tissue for growth
      hormone action. Future investigations are needed to investigate further the role
      of growth hormone in the development of leiomyomas.

PMID- 7573250
TI  - Chronic fungal vaginitis: the value of cultures.
AB  - OBJECTIVE: Our purpose was to examine the importance of fungal cultures in
      evaluating patients with symptoms of chronic vaginitis by assessing the relative
      contribution of various yeast species and by comparing infections caused by
      Candida albicans with those caused by other species. STUDY DESIGN: A prospective
      observational study of patients referred with chronic vaginal symptoms was
      undertaken. In addition to a standard evaluation of symptoms, cultures for yeast
      were performed on modified Sabouraud agar plates. RESULTS: Seventy-seven isolates
      were obtained from 74 patients. A total of 68% were Candida albicans; 32% were
      other species. The clinical syndromes caused by non-Candida albicans isolates
      were indistinguishable from Candida albicans infections. Fluconazole gave a short
      term mycologic cure in all Candida albicans but only 25% of non-Candida albicans
      cases (p < 0.001). In non-Candida albicans infections, boric acid suppositories
      achieved the best mycologic cure rate (85%). CONCLUSION: Because non-Candida
      albicans species are responsible for a significant number of chronic fungal
      vaginal infections and are more resistant to therapy with fluconazole, fungal
      cultures are a valuable aid in confirming the diagnosis and selecting appropriate
      therapy.

PMID- 7573252
TI  - Kininogen present in rat reproductive tissues is apparently synthesized by the
      liver, not by the reproductive system.
AB  - OBJECTIVE: The purpose of this study was to determine the source(s) of the
      reproductive tract kininogen and to assess whether kininogen transcription is
      influenced by reproductive conditions. STUDY DESIGN: Rats in various reproductive
      states (immature, mature, ovulatory, luteal phase, pregnancy, parturition,
      postpartum) were used to obtain reproductive tissues (follicles, corpora lutea,
      oviduct, uterus, testes) and liver. Complementary deoxyribonucleic acid probes
      for rat prekininogens were used to quantify kininogen messenger ribonucleic acid
      synthesis. RESULTS: The T-prekininogen complementary deoxyribonucleic acid probe
      detected a single 1.6 kb message, whereas the k-prekininogen complementary
      deoxyribonucleic acid probe identified two messages, an abundantly expressed 1.6
      kb band and a 2.2 kb band. The source of all the three prekininogen messages
      appears to be the liver. Naturally occurring reproductive conditions such as
      ovulation, implantation, and parturition, did not turn on prekininogen message
      transcription in the rat gonad or genital tract. Only decidualization of the
      uterus was associated with the induction of kininogen transcription in the liver.
      CONCLUSION: There appears to be little, if any, contribution of local gene
      expression to the kininogen present in the reproductive tissues. Apparently, the
      reproductive tract increases uptake of kininogen from plasma as needed.

PMID- 7573253
TI  - Age at menarche among diethylstilbestrol granddaughters.
AB  - We interviewed 542 women whose mothers were in a randomized trial of
      diethylstilbestrol. Effects of diethylstilbestrol on the third generation were
      explored by ascertaining age at menarche for the women's daughters. A total of
      123 daughters were > or = 10 years old (52 exposed and 71 unexposed). Age at
      menarche was unaffected by mother's prenatal diethylstilbestrol exposure.

PMID- 7573251
TI  - Effects of a gonadotropin-releasing hormone agonist on the calcium-parathyroid
      axis and bone turnover in women with endometriosis.
AB  - OBJECTIVE: Our purpose was to investigate the effects of nafarelin on bone
      turnover and mass (bone mineral density, in grams per square centimeter) in women
      with endometriosis. STUDY DESIGN: We monitored 22 young women with endometriosis
      during and 6 months after 6 months of nafarelin treatment. We compared the bone
      mineral density status of these women with that of healthy controls undergoing
      sequential bone mineral density measurement. RESULTS: Subjects had a 2.2% loss in
      L2-4 bone mineral density by 6 months, increasing 3 months later to 3% and
      returning toward baseline by 6 months after treatment. Radius bone mineral
      density did not change in the treatment group. Bone mineral density did not
      change in controls. Serum and urinary calcium levels rose during treatment.
      Hydroxyproline excretion increased and remained elevated 6 months after
      treatment. A rise in serum osteocalcin persisted 3 months after therapy but
      normalized by 6 months. CONCLUSIONS: Bone mineral density deficits with nafarelin
      are reversible. Increased bone turnover persists 6 months beyond treatment,
      demonstrating the need for careful monitoring of women receiving prolonged or
      repeated treatment.

PMID- 7573254
TI  - Prenatal screening for group B Streptococcus. I. Impact of antepartum screening
      on antenatal prophylaxis and intrapartum care.
AB  - OBJECTIVE: Our purpose was to evaluate current obstetric practice regarding
      screening and prophylaxis for group B Streptococcus and to evaluate the impact of
      screening on antepartum and intrapartum care. STUDY DESIGN: A total of 1232
      members of the Society of Perinatal Obstetricians were asked to indicate their
      practices regarding screening for group B Streptococcus. Respondents were then
      asked their practices regarding antepartum and intrapartum prophylaxis on the
      basis of screening cultures, prior antimicrobial treatment, and other risk
      factors for neonatal sepsis. RESULTS: Of the 925 respondents (75.1%), 30.8%
      performed routine screening in all pregnancies: first prenatal visit (42.3%), 26
      to 28 weeks (41.3%), and 34 to 38 weeks (22.1%). In addition, 65.9% would screen
      patients only under high-risk situations. Although 70.5% sample multiple sites,
      respondents were inconsistent regarding the sites from which cultures are
      obtained: distal vagina (64.2%), cervix (53.9%), proximal vagina (40.0%), anal
      canal (38.5%), and urethra (4.3%). A total of 34.7% of respondents would treat
      the patient at the time of a positive culture. Knowledge of maternal group B
      Streptococcus carriage would significantly alter intrapartum prophylaxis in low
      risk (60.3% vs 0.5%) and various high-risk populations (74.0% to 98.4% vs 11.3%
      to 55.0%). However, no consensus as to optimal practice was identified.
      CONCLUSIONS: This survey demonstrates significant inconsistencies in screening
      and prophylaxis for group B Streptococcus by specialists in maternal-fetal
      medicine. In addition, it reveals that the recommendations of The American
      College of Obstetricians and Gynecologists and the American Academy of Pediatrics
      are not routinely followed by these specialists. Knowledge of group B
      Streptococcus carriage significantly increases antepartum and intrapartum
      treatment regardless of the presence of other risk factors for neonatal sepsis.
      The impact of this practice on neonatal therapy warrants further evaluation.

PMID- 7573256
TI  - Computer-generated admission forms have greater accuracy.
AB  - We examined the accuracy of computer-generated admission forms to standardized
      handwritten admission forms for 40 patient records. There was a mean of 8.3
      errors among handwritten forms but only 0.9 errors among computerized forms (p <
      0.0001). Written forms had seven serious errors versus one for computerized forms
      (p < 0.05). We conclude that computerized admission forms have superior accuracy.

PMID- 7573255
TI  - Prenatal screening for group B Streptococcus. II. Impact of antepartum screening
      and prophylaxis on neonatal care.
AB  - OBJECTIVES: Our purpose was to evaluate the current practice of antimicrobial
      prophylaxis of preterm and low-birth-weight infants and to determine the impact
      of intrapartum fever, group B Streptococcus carriage, intrapartum antimicrobial
      therapy, and duration of membrane rupture on neonatal therapy. STUDY DESIGN: A
      total of 1356 members of the American Academy of Pediatrics were asked their
      practice regarding neonatal screening and antimicrobial prophylaxis. Respondents
      were asked to define how maternal fever, group B Streptococcus carriage,
      intrapartum antimicrobial therapy, and prolonged membrane rupture would affect
      their decisions regarding neonatal therapy. RESULTS: A total of 982 responses
      were obtained (72.4%). Routine antimicrobial prophylaxis is given to asymptomatic
      preterm neonates by 33.7% of pediatricians. Prophylaxis is inconsistently given
      at 32 to 36 weeks but is nearly universal after intrapartum fever, regardless of
      intrapartum therapy. If empiric intrapartum prophylaxis was given before a
      preterm birth, both the incidence (47.1% vs 29.1%) and frequency of prolonged
      neonatal therapy (30.1% vs 17.4% > or = 7 days) would be increased. Knowledge of
      maternal group B Streptococcus carriage would lead to a 2.6-fold increase in
      treatment (75.1% vs 29.1%) and 1.8-fold increase in the incidence of prolonged
      therapy of preterm infants (30.9% vs 17.4%), with 45.3% giving antibiotics for >
      or = 1 week if intrapartum treatment had been instituted. Surprisingly, 18% of
      pediatricians would treat term neonates without any risk factors other than
      maternal group B streptococcal carriage, and 32.7% would continue treatment for >
      or = 7 days. The majority of pediatricians (82.6%) felt that intrapartum
      prophylaxis would reduce early-onset group B streptococcal sepsis, but only 46.0%
      felt overall neonatal sepsis would be decreased by such therapy. CONCLUSIONS:
      Antepartum screening and intrapartum prophylaxis against group B Streptococcus by
      obstetricians may lead to an increased incidence and duration of treatment of
      preterm and term neonates by the pediatrician. The efficacy, cost, and risk of
      such treatment in broadly applied screening and treatment programs should be
      considered before a standard of care is established.

PMID- 7573257
TI  - The association between occupational factors and preterm birth: a United States
      nurses' study. Research Committee of the Association of Women's Health,
      Obstetric, and Neonatal Nurses.
AB  - OBJECTIVE: Our purpose was to evaluate factors associated with preterm birth
      among a national sample of U.S. nurses. STUDY DESIGN: We conducted a case-control
      study of 210 nurses whose infants were delivered prematurely (< 37 weeks) (cases)
      and 1260 nurses whose infants were delivered at term (> or = 37 weeks)
      (controls). An occupational fatigue score was constructed from four sources and
      varied from 0 to 4. The relation between occupational activity (including hours
      working and fatigue score) and preterm birth was analyzed with the use of Pearson
      chi 2 tests, estimates of odds ratios with 95% confidence intervals, and
      multivariate logistic regression; we controlled for confounding factors. RESULTS:
      Factors significantly associated with preterm birth included hours worked per
      week (p < 0.002), per shift (p < 0.001), and while standing (p < 0.001); noise (p
      = 0.005); physical exertion (p = 0.01); and occupational fatigue score (p <
      0.002). The adjusted odds ratios were 1.6 (p = 0.006) for hours worked per week
      (< or = 36 vs > 36) and 1.4 (p = 0.02) for fatigue score < 3 vs > or = 3.
      CONCLUSIONS: Preterm birth among working women may be related to hours worked per
      day or week and to adverse working conditions.

PMID- 7573258
TI  - Successful pregnancy in association with Zollinger-Ellison syndrome.
AB  - Persistent severe vomiting in pregnancy may be caused by underlying disease and
      should be investigated. A patient with intractable vomiting associated with
      abdominal pain and dental enamel erosion in two pregnancies had a gastrinoma.
      Symptoms were successfully controlled with omeprazole in a third pregnancy. All
      three babies were healthy.

PMID- 7573259
TI  - The angiotensin sensitivity test and low-dose aspirin are ineffective methods to
      predict and prevent hypertensive disorders in nulliparous pregnancy.
AB  - OBJECTIVE: Our purpose was to assess the efficiency of the angiotensin
      sensitivity test as a predictive test for preeclampsia and the effectiveness of
      low-dose aspirin to prevent preeclampsia when commenced at 28 weeks' gestation in
      angiotensin II-sensitive women. STUDY DESIGN: A total of 495 healthy nulliparous
      women underwent the angiotensin sensitivity test at 28 weeks' gestation. The
      angiotensin II-sensitive women were randomized to 60 mg of aspirin or placebo as
      a subset of a large multicenter, randomized, controlled trial of low-dose aspirin
      therapy in pregnancy. Assessment of the efficiency of the angiotensin sensitivity
      test and low-dose aspirin in pregnancy was performed after detailed review of
      case notes after delivery. The Oxford definition of preeclampsia was used. This
      includes women without proteinuria but requires blood pressure increments that
      have been validated to bias the selection to primigravid women. RESULTS: Five
      women had proteinuric preeclampsia in the angiotensin II-sensitive group
      randomized to aspirin compared with none in the group randomized to placebo.
      Overall, 11 (25%) of the women randomized to aspirin had preeclampsia compared
      with four (11%) randomized to placebo (p < 0.05, not significant). The positive
      and negative predictive values for the angiotensin sensitivity test were 19% and
      87%, respectively. CONCLUSION: The angiotensin sensitivity test is not an
      effective screening test for preeclampsia, and low-dose aspirin does not prevent
      preeclampsia when commenced at 28 weeks' gestation in angiotensin II-sensitive
      women.

PMID- 7573260
TI  - Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy:
      a randomized placebo-controlled study.
AB  - OBJECTIVE: Our purpose was to study the effects of isradipine, a dihydropyridine
      calcium channel blocker, on mother and fetus in the treatment of hypertensive
      disorders of pregnancy. STUDY DESIGN: The investigation was performed as a two
      group, parallel, double-blind multicenter study of isradipine versus placebo.
      Fifty-four women were randomized to treatment with isradipine slow-release
      capsules given orally 5 mg twice a day and 57 to a placebo group. RESULTS:
      Isradipine lowered the maternal mean arterial blood pressure effectively in women
      with nonproteinuric hypertension but did not do so in women with proteinuria at
      recruitment or appearing during treatment. Blood flow in the umbilical artery and
      maternal renal and liver function were not influenced by treatment. Isradipine
      had few side effects and was well tolerated. CONCLUSION: Calcium channel blockade
      with isradipine is effective for treatment of nonproteinuric hypertension but not
      in preeclampsia.

PMID- 7573261
TI  - "Physiologic" intracellular acidosis in pregnancy.
AB  - To investigate acid-base homeostasis in pregnancy, we used phosphorus 31 nuclear
      magnetic resonance spectroscopy to measure intracellular pH in erythrocytes from
      nonpregnant (n = 33) and third-trimester pregnant women (n = 22). Intracellular
      pH was lower in pregnant compared with nonpregnant controls (7.23 +/- 0.015 vs
      7.29 +/- 0.012, p = 0.003). We hypothesize that this "physiologic" intracellular
      acidosis of pregnancy potentiates oxygen-hemoglobin dissociation and oxygen
      delivery across the placenta.

PMID- 7573262
TI  - Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind,
      placebo-controlled trial.
AB  - OBJECTIVE: Our purpose was to determine the effectiveness of pyridoxine for
      nausea and vomiting of pregnancy. STUDY DESIGN: During an 11-month period 342
      women who first attended Chiang Mai University Hospital antenatal clinic at < or
      = 17 weeks' gestation were randomized to received either oral pyridoxine
      hydrochloride, 30 mg per day, or placebo in a double-blind fashion. Patients
      graded the severity of their nausea by a visual analog scale and recorded the
      number of vomiting episodes over the previous 24 hours before treatment and again
      during 5 consecutive days on treatment. RESULTS: There was a significant decrease
      in the mean of posttherapy minus baseline nausea scores in the pyridoxine
      compared with that in the placebo group (t test, p = 0.0008). There was also a
      greater reduction in the mean number of vomiting episodes, but the differences
      did not reach statistical significance (p = 0.0552). CONCLUSION: Pyridoxine is
      effective in relieving the severity of nausea in early pregnancy.

PMID- 7573263
TI  - Thrombocytopenia in pregnant women who use cocaine.
AB  - OBJECTIVE: Our purpose was to determine the prevalence of cocaine-associated
      thrombocytopenia. STUDY DESIGN: This cohort study was conducted in an inner-city
      prenatal center. A total of 1907 patients were screened by the Mother's Project,
      which is an intervention project for inner-city cocaine-abusing parturients.
      Platelet counts were grouped by illicit drug usage. RESULTS: Platelet counts were
      available in 37% (709) of subjects; there were no differences between subjects
      with available platelet counts and those without on illicit drug use or other
      demographic measures. Five groups were defined: drug-free group (n = 331),
      cocaine group (n = 104), cocaine and opiates group (n = 11), opiates group (n =
      18), and other-drug group (n = 236). Nineteen subjects had a low platelet count
      (< 150 x 10(9)/L). The medical records of all subjects with a low platelet count
      were reviewed for any medical condition known to be associated with
      thrombocytopenia, and two subjects were excluded. The rate of thrombocytopenia in
      the drug-free group was 1.5%, whereas the rate in the cocaine group was 6.7%
      (relative risk 4.4, p < 0.05). Because of the reported association of
      thrombocytopenia with seropositive human immunodeficiency virus status,
      seropositive women were excluded from the analysis. Even after human
      immunodeficiency virus status adjustments for the estimated rate, the cocaine
      using group continued to have a significantly higher rate of thrombocytopenia
      (5.4% to 7.2% vs 1.23% to 1.26%, p < 0.05 to p < 0.005). CONCLUSIONS: These
      results indicate that cocaine use is an independent risk factor for
      thrombocytopenia in an inner-city parturient population.

PMID- 7573264
TI  - Ultrasonographic bone characteristics during normal pregnancy: longitudinal and
      cross-sectional evaluation.
AB  - OBJECTIVE: We evaluated the pattern of bone density during pregnancy by radiation
      free ultrasonographic densitometry. STUDY DESIGN: In a longitudinal study we
      measured bone mineral density in a group of 10 normal primiparous women, from the
      fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study
      bone mineral density was determined in a group of 85 normal primiparous women, in
      different weeks of pregnancy. RESULTS: In the longitudinal study ultrasonographic
      bone density was stable in the first part of pregnancy, whereas a significant (p
      < 0.05) decrease was evidenced during the third trimester. A negative correlation
      between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the
      cross-sectional study. CONCLUSION: During physiologic pregnancy the calcium
      mobilization from the maternal bone stores to accomplish the fetal needs can
      cause a significant decrease in maternal bone density in the last trimester of
      gestation.

PMID- 7573265
TI  - Impact of health education during pregnancy on behavior and utilization of health
      resources. Latin American Network for Perinatal and Reproductive Research.
AB  - OBJECTIVE: Our purpose was to assess whether an intervention in the education of
      the mother and the support person involves a change in health-related behavior
      and use of health facilities. STUDY DESIGN: A randomized, controlled trial was
      conducted in four cities of Latin America on pregnant women at risk. Half of them
      (n = 1115) received a home intervention of four to six visits dealing with
      psychosocial support and education about health-related habits, alarm signs,
      hospital facilities, antismoking and antialcohol programs, and a reinforcement of
      adequate health services utilization for the pregnant woman and a support person.
      The control group (n = 1120) received routine prenatal care. RESULTS: The
      distribution of risk factors and demographic, obstetric, and psychologic
      characteristics at baseline was similar in both groups. Women in the intervention
      group showed a statistically significant better knowledge of seven of the nine
      alarm signs considered and of two of the three labor-onset signs required. No
      differences between groups were observed in improvement on diet, cigarette and
      alcohol consumption, maternal physical strain, lactation at 40 days postpartum,
      and utilization of health facilities. CONCLUSIONS: An intervention of
      psychosocial support and health education during pregnancy failed to show any
      benefit on perinatal outcome, health-related behavior, or utilization of health
      facilities.

PMID- 7573266
TI  - Soluble tumor necrosis factor receptors in maternal plasma and second-trimester
      amniotic fluid.
AB  - OBJECTIVES: We assessed maternal plasma and second-trimester amniotic fluid for
      levels of the p55 and p75 soluble tumor necrosis factor receptors. STUDY DESIGN:
      Blood was drawn from 61 healthy pregnant women (group A) before second-trimester
      genetic amniocentesis, and an aliquot of amniotic fluid was also obtained for
      this study. An additional blood sample was obtained from 13 of these patients at
      36 to 40 weeks' gestation. Twenty-three healthy, nonpregnant women of
      reproductive age donated blood as a control group (group B). All plasma and
      amniotic fluid specimens were collectively assayed for the p55 and p75 soluble
      tumor necrosis factor receptors by specific enzyme-linked immunoassays.
      Additionally, tumor necrosis factor-alpha concentrations were measured in second
      trimester plasma and amniotic fluid of 22 patients in group A and in all 23 of
      the nonpregnant women. RESULTS: The p55 and p75 soluble tumor necrosis factor
      receptors were detectable in all plasma samples from both groups of patients. The
      concentrations of both soluble receptors were significantly higher in second
      trimester plasma compared with nonpregnant measurements (p < 0.01), and the
      plasma concentrations of both soluble receptors increased significantly from the
      second to third trimester (p < 0.01). The p55 and p75 soluble tumor necrosis
      factor receptors were also detectable in all amniotic fluid samples. Tumor
      necrosis factor-alpha was detected in the plasma of 15 of 22 patients in the
      second trimester but in none of the amniotic fluid samples and in none of the
      plasma samples from the nonpregnant cohort. CONCLUSIONS: Both the p55 and p75
      soluble tumor necrosis factor receptors are physiologic constituents of second
      trimester maternal plasma and amniotic fluid. Concentrations are elevated in
      pregnancy and further increase from the second to third trimester.

PMID- 7573267
TI  - Perinatal outcome in relation to second-stage duration.
AB  - OBJECTIVE: The second stage of labor has been thought of as a time of particular
      asphyxial risk for the fetus. This perceived risk has been invoked to justify
      arbitrary time limits and high rates of operative vaginal delivery. The purpose
      of this study was to determine whether perinatal outcome worsened as the second
      stage lengthened. STUDY DESIGN: Over a 5-year period at one university teaching
      hospital, 6041 nulliparous women reached the second stage of labor with a live
      singleton cephalic fetus with birth weight > or = 2500 gm. A retrospective review
      of perinatal morbidity and mortality was performed and the results related to the
      duration of the second stage. RESULTS: The second stage lasted > 3 hours in 11%
      of nulliparous women and > 5 hours in 2.7%. There were no perinatals death
      unrelated to anomaly. There was no significant relationship between second-stage
      duration and low 5-minute Apgar score, neonatal seizures, or admission to the
      neonatal intensive care unit. CONCLUSION: Operative intervention in the second
      stage is not warranted merely because some set number of hours has elapsed.

PMID- 7573268
TI  - The pharmacokinetics of the oxytocin antagonist atosiban in pregnant women with
      preterm uterine contractions.
AB  - OBJECTIVE: Our purpose was to evaluate the pharmacokinetics of atosiban, an
      oxytocin antagonist, during and after intravenous infusion in pregnant patients
      having at least six contractions per hour. The relationship between atosiban
      infusion and uterine activity was also assessed. STUDY DESIGN: Plasma samples
      from eight pregnant patients treated with intravenous atosiban (300
      micrograms/min for 6 to 12 hours) were analyzed for atosiban concentration by a
      specific radioimmunoassay procedure. Contraction rate data were obtained by
      external tocodynamometry for 1 hour before the infusion and during the subsequent
      infusion. RESULTS: The average steady-state plasma concentrations of patients
      receiving intravenous atosiban were 442 +/- 73 ng/ml (mean +/- SD), with steady
      state achieved by 1 hour after the start of the infusion. After the completion of
      the infusion, plasma concentrations declined rapidly in a biexponential manner
      with initial and terminal half-life estimates of 13 +/- 3 and 102 +/- 18 minutes,
      respectively. The effective half-life was 18 +/- 3 minutes. The plasma clearance
      of atosiban was relatively high (42 L/hr) and the volume of distribution
      (approximately 18 L) was consistent with distribution into extracellular fluid.
      Of the seven patients evaluated for uterine activity, the mean contraction rate
      decreased by 75% during the third hour of treatment and remained low until
      treatment termination. CONCLUSION: On the basis of earlier published reports, the
      pharmacokinetics of atosiban in pregnant patients are similar to those in
      nonpregnant women. Although the patient population was small, a consistent
      reduction in uterine activity was observed during atosiban infusion.

PMID- 7573269
TI  - Effect of serum on secretion of prostacyclin and endothelin-1 by decidual
      endothelial cells from normal and preeclamptic pregnancies.
AB  - OBJECTIVE: Increasing circumstantial evidence suggests that the maternal
      endothelial cell is centrally involved in the syndrome of preeclampsia, and a
      number of reports have described the presence of a factor(s) that alters
      endothelial cell function in serum from women with preeclampsia. We have
      previously described differences between endothelial cells from the decidual
      vascular bed and those from the umbilical vein. The purposes of this study were
      (1) to examine the effect of serum from normal and preeclamptic women on
      secretion of vasoactive substances by maternal decidual endothelial cells, (2) to
      compare these results with those from umbilical vein endothelial cells, widely
      used as a surrogate for endothelial cells in general, (3) to compare responses to
      these sera by decidual endothelial cells from normal and preeclamptic
      pregnancies, and (4) to determine whether these responses are amplified by
      preincubation in test sera. STUDY DESIGN: Endothelial cells were isolated from
      umbilical veins and from decidual biopsy specimens collected at caesarean section
      delivery, from both normal and preeclamptic women. Cells were maintained in
      culture until passage 2, when secretion by the three endothelial cell populations
      of the vasodilator prostacyclin (measured as its stable metabolite, 6-keto
      prostaglandin F1 alpha) and the vasoconstrictor endothelin-1 was compared in the
      presence of serum from preeclamptic or gestational age-matched normal pregnant
      women. RESULTS: Prostacyclin secretion by all endothelial cell populations was
      higher in the presence of serum from preeclamptic women than in medium containing
      serum from gestational age-matched normal pregnant women. Values for endothelin
      were not significantly different in cells incubated in serum from normal or
      preeclamptic women. Preincubation of decidual cells from preeclamptic women in
      test serum, particularly in preeclamptic serum, resulted in more marked
      stimulation of prostacyclin secretion. CONCLUSIONS: Preeclamptic serum contains a
      factor(s) that stimulates prostanoid secretion from endothelial cells. This
      effect was observed in both umbilical vein and decidual cells. Cells from
      preeclamptic women were more susceptible to perturbation of their secretion by
      this factor. Serum from preeclamptic women did not specifically affect endothelin
      1 secretion.

PMID- 7573270
TI  - Use of cardiac index in pregnancy: is it justified?
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that standardization
      of cardiac output in pregnancy by correcting for body surface area, and thus
      obtaining cardiac index, is justified. STUDY DESIGN: Cardiac output was
      determined by thoracic electrical bioimpedance monitoring in 78 pregnant women;
      recordings were made at 1-month intervals from the first antenatal visit and a
      further two were made during the sixth and twelfth weeks after delivery. In a
      separate group of 10 pregnant women, cardiac output was determined by Doppler
      echocardiography at 5, 10, 14, 25, and 35 weeks and at 12 weeks post partum.
      RESULTS: Irrespective of gestational age, the correlation between cardiac output
      and body surface area was poor, by either thoracic electrical bioimpedance
      monitoring (r = 0.15 to 0.39) or Doppler echocardiography (r = 0.00 to 0.29).
      Furthermore, strict proportionality between cardiac output and body surface area
      was in general not the best way of describing the (poor) relation between these
      two. CONCLUSION: Standardization of cardiac output in pregnancy by correcting for
      body surface area to compare cardiac performance between individuals and between
      groups of individuals is not justified.

PMID- 7573271
TI  - The feasibility of a control population for a randomized control trial of seizure
      prophylaxis in the hypertensive disorders of pregnancy.
AB  - OBJECTIVE: To document the feasibility of a control population for a randomized
      controlled trial, we report our experience in managing hypertensive pregnancies
      without seizure prophylaxis. STUDY DESIGN: An 8-year cross-sectional study in one
      institution was performed of all hypertensive patients. RESULTS: Of 467 patients
      with preeclampsia or superimposed preeclampsia managed without seizure
      prophylaxis, 18 had seizure activity, 3.9% (95% confidence interval 2.3% to
      6.0%). There was no seizure-related maternal mortality or major morbidity, and
      the perinatal mortality rate after 28 gestational weeks was the same in patients
      with or without seizures. By logistic regression seizures were 17.4 times more
      likely in preeclampsia and 8.1 times more likely in chronic hypertension with
      superimposed preeclampsia, compared with gestational or chronic hypertension
      alone. CONCLUSION: The rate of seizures in patients with preeclampsia or
      superimposed preeclampsia managed without seizure prophylaxis was low and
      unassociated with an increase in maternal or perinatal mortality. A control arm
      is feasible in a randomized, controlled trial to address the issue of whether
      antiseizure medication can prevent eclampsia.

PMID- 7573272
TI  - Women cannot discriminate between different paracervical block techniques applied
      to opposite sides of the cervix.
AB  - The purpose of this study was to determine whether women can discriminate better
      from less effective paracervical block techniques applied to opposite sides of
      the cervix. If this discrimination could be made, it would be possible to compare
      different techniques and thus improve the quality of paracervical anesthesia. Two
      milliliters of local anesthetic was applied to one side and 6 ml to the other
      side of volunteers' cervices before cervical dilation. Statistical examination
      was by sequential analysis. The study was stopped after 47 subjects had entered,
      when sequential analysis found that there was no significant difference in
      women's perception of pain. Nine women reported more pain on the side with more
      anesthesia and eight reported more pain on the side with less anesthesia. Because
      the amount of anesthesia did not make a difference, the null hypothesis (that
      women cannot discriminate between different anesthetic techniques) was accepted.
      Women are not able to discriminate different doses of local anesthetic when
      applied to opposite sides of the cervix.

PMID- 7573273
TI  - Levels of hepatocyte growth factor in maternal serum and amniotic fluid.
AB  - OBJECTIVE: The purpose of our study was to investigate hepatocyte growth factor
      levels in maternal serum and amniotic fluid during pregnancy. We also
      demonstrated production and secretion of hepatocyte growth factor by placenta and
      amnion at different stages of gestation. STUDY DESIGN: Hepatocyte growth factor
      levels in maternal serum (n = 219), cord blood (n = 20), and amniotic fluid
      samples (n = 90) were measured by an enzyme-linked immunosorbent assay. The
      secretion of hepatocyte growth factor by placenta and amnion was evaluated by
      measuring the amount released into the culture supernatant. RESULTS: Most
      hepatocyte growth factor levels in maternal serum were below the detection limit
      before 10 weeks of pregnancy. Levels increased significantly thereafter and
      continued to increase until term. On the other hand, levels in amniotic fluid
      were significantly higher between 20 and 29 weeks of gestation than after 30
      weeks. Hepatocyte growth factor secretion from the placental tissue per weight
      seemed unchanged throughout pregnancy. Its secretion from amnion was, however,
      approximately 300 to 400-fold higher in the second trimester compared with that
      at term. CONCLUSION: Both placenta and amnion produce and secrete hepatocyte
      growth factor, suggesting its role in fetal growth and the growth and
      differentiation of placenta.

PMID- 7573274
TI  - Accuracy and intraobserver variability of simulated cervical dilatation
      measurements.
AB  - OBJECTIVE: Our purpose was to assess the accuracy and intraobserver variability
      of clinical cervical diameter measurements among obstetric health care providers.
      STUDY DESIGN: Polyvinyl chloride pipes 1 to 10 cm in diameter were mounted in
      cardboard boxes and used to simulate cervical examinations. The boxes were
      designed so that the examiner had to rely solely on proprioception to determine
      the inner diameter. RESULTS: A total of 1574 simulated cervical diameter
      measurements were obtained from 102 different examiners in a two-part study. The
      overall accuracy for determining the exact diameter was 56.3%, which improved to
      89.5% when an error of +/- 1 cm was allowed. Intraobserver variability for a
      given diameter measurement was 52.1%, which decreased to 10.5% when an error of
      +/- 1 cm was allowed. CONCLUSIONS: Cervical diameter measurements obtained by
      digital examination are precise when an error of +/- 1 cm is allowed for.
      Intraobserver variability is > 50% and is an important consideration when
      evaluating dysfunctional labor.

PMID- 7573275
TI  - The in-training examination in obstetrics and gynecology: an attempt to establish
      a remediation indicator.
AB  - OBJECTIVE: With the use of a university- and community hospital-based faculty, we
      attempted to determine at what performance level remediation would be
      recommended. STUDY DESIGN: The Committee on In-Training Examinations for
      Residents in Obstetrics and Gynecology Task Force on Standard-Based Scoring sent
      the 1991 examination to 16 university- and 12 community hospital-based faculty
      members. Given a standardized definition of a "borderline third-year resident,"
      each faculty scored each item on the examination on whether that hypothetic
      resident would or would not correctly answer the item. RESULTS: The mean
      expectation of correct responses on the 397-item test was 236 (59%). This was
      identical to the score obtained if 2 SDs were subtracted from the actual mean for
      all third-year residents taking the examination. University- and community
      hospital-based faculty members had generally similar expectations of this defined
      resident. CONCLUSION: Although poor examination results should not be recommended
      as the sole determinant for promotion, it appears that 2 SDs below the mean may
      be an appropriate score below which remediation could be recommended.

PMID- 7573277
TI  - Prenatal diagnosis of congenital cytomegalovirus infection with abnormal triple
      screen results and hyperechoic fetal bowel.
AB  - A 14-year-old primigravid adolescent with abnormal triple-marker screen results
      at 18 weeks' gestation was found to have hyperechoic fetal bowel. Amniotic fluid
      culture was positive for cytomegalovirus. Serial ultrasonography demonstrated
      progressive lateral ventriculomegaly, intrauterine growth retardation, and
      hydrops fetalis; fetal death occurred at 32 weeks' gestation.

PMID- 7573276
TI  - The role of infection in premature rupture of the membranes. 1950.

PMID- 7573278
TI  - Significance of prenatal diagnosis of umbilical cord cyst in a fetus with trisomy
      18.
AB  - An umbilical cord cyst was detected in a fetus who underwent ultrasonography at
      38 weeks' gestation for clinical suspicion of intrauterine growth retardation.
      Such an association should alert the clinician to the possibility of aneuploidy,
      thus guiding clinical management. This case represents the second report of a
      cystic umbilical lesion in a fetus with trisomy 18.

PMID- 7573279
TI  - Intractable bleeding managed with Foley catheter tamponade after dilation and
      evacuation.
AB  - Hemorrhage is one of the most frequent complications after dilation and
      evacuation. A small fraction of patients with hemorrhage will not respond to
      standard therapies. We discuss a case where both reaspiration and standard
      pharmacologic therapy failed to control hemorrhage and where hemorrhage was
      ultimately controlled by tamponade with two Foley catheters. We propose this
      method as an additional alternative for controlling hemorrhage after dilation and
      evacuation before resorting to angiographic embolization or surgery.

PMID- 7573280
TI  - Grapelike leiomyoma of the uterus.
AB  - A 24-year-old nulliparous woman underwent laparotomy for a large pelvic mass.
      Grapelike tumor extending from the uterus into the broad ligaments and peritoneal
      cavity was found. A diagnosis of sarcoma appeared likely, but radical surgery was
      avoided when frozen sections indicated a histologically benign smooth muscle
      tumor.

PMID- 7573281
TI  - First report of a vaginal foreign body perforating into the retroperitoneum.
AB  - Pelvic examination of a 19-year-old woman with recurrent pain after multiple
      laparotomies revealed a 4.0 cm paracervical fibroepithelial polyp and tender
      fullness in the left pelvis. Abdominal exploration had normal findings, but
      exploration of the retroperitoneum revealed an encysted bottle cap that had
      eroded through the vaginal wall years before.

PMID- 7573283
TI  - Pelvic endometriosis mimicking advanced ovarian cancer: presentation with pleural
      effusion, ascites, and elevated serum CA 125 level.
AB  - Two patients with clinical complications of endometriosis mimicking stage IV
      epithelial ovarian cancer are described. One had bilateral pleural effusions,
      ascites, and a serum CA 125 level of 440 U/ml. The other had a right-sided
      pleural effusion and a large abdominal mass.

PMID- 7573282
TI  - Tuboovarian abscess caused by Edwardsiella tarda.
AB  - Edwardsiella tarda infections are uncommon and have often been reported in
      association with pet reptiles. The majority of these infections occur as
      gastrointestinal disorders in immunocompromised hosts. We believe this to be the
      first reported American case of tuboovarian abscess caused by this organism in an
      otherwise healthy woman whose only known exposure was to raw seafood. This
      patient had fever and lower abdominal pain caused by a severe Edwardsiella tarda
      pelvic abscess that required surgical drainage and intravenous antibiotics for
      complete recovery.

PMID- 7573284
TI  - Thrombolytic therapy for basilar artery thrombosis in the puerperium.
AB  - A case is presented of a woman in whom basilar artery thrombosis developed 14
      days post partum. She was successfully treated with intraarterial urokinase. This
      case demonstrates that complete neurologic recovery can be achieved after
      recanalization of the basilar artery with thrombolytic therapy.

PMID- 7573285
TI  - Sturge-Weber syndrome in pregnancy.
AB  - Sturge-Weber syndrome is a rare disease involving a port-wine facial nevus and an
      associated intracranial venous malformation. There are no reports of this
      disorder in association with pregnancy in the English literature, and the effects
      of pregnancy on this syndrome remain unknown. We present a case of Sturge-Weber
      syndrome diagnosed in the early postpartum period and document the possible
      deleterious effects of gestation on the neurologic symptoms and ultimate
      prognosis.

PMID- 7573286
TI  - A case of splenosis masquerading as endometriosis.
AB  - Splenosis represents the autotransplantation of splenic tissue after splenic
      trauma or surgery. Characterized by bluish implants diffusely scattered
      throughout the peritoneal cavity, splenosis is frequently mistaken for
      endometriosis. A 19-year-old woman was referred for "extensive endometriosis"
      found at diagnostic laparoscopy by her gynecologist. After extensive resection of
      peritoneal, pelvic, and intestinal implants of typical and "atypical"
      endometriosis, the "atypical" endometriosis was reported by the pathologist to be
      splenosis. Because splenosis is not a pathologic process but may actually be
      beneficial to the patient, it is important to recognize splenosis and not confuse
      it with endometriosis, malignancy, or hemangioma.

PMID- 7573287
TI  - Maternal oxygen administration and fetal well-being.

PMID- 7573288
TI  - Estimation of Down syndrome risk in a donor egg pregnancy.

PMID- 7573289
TI  - Contractions are not always labor.

PMID- 7573290
TI  - Transvaginal endoscopic oophorectomy.

PMID- 7573291
TI  - Maternal serum screening should not replace amniocentesis.

PMID- 7573293
TI  - Acquired immunodeficiency syndrome-related Kaposi's sarcoma: two cervical cases.

PMID- 7573292
TI  - Endothelial dysfunction yes, cytotoxicity no!

PMID- 7573294
TI  - Estrogen replacement: the evolving role of alternative delivery systems.
      Introduction.

PMID- 7573295
TI  - Benefits and risks of estrogen replacement therapy.
AB  - Estrogen replacement therapy (ERT) has been shown to reduce the risk of
      cardiovascular disease (CVD) and osteoporosis in postmenopausal women. Studies
      also indicate a reduced risk of stroke and its consequent mortality among
      estrogen users, and ERT may also have a role in reducing the risk of Alzheimer's
      disease and increasing a woman's overall quality of life. On the negative side,
      some studies show a small duration-related risk of breast cancer with estrogen
      use and a significant increase in endometrial cancer; the latter is virtually
      eliminated with the addition of a progestin to the regimen. Although the
      definitive answer is not yet available, recent epidemiologic data suggest no
      reduction in protection against CVD and bone fracture with the addition of
      progestin, which is referred to as hormone replacement therapy, as opposed to
      using estrogen alone. A woman's potential risks associated with ERT or hormone
      replacement therapy must be weighed against her lifetime risks of developing CVD,
      stroke, and bone fracture. The reduction in mortality and morbidity rates with
      hormone use is generally viewed to be substantial and cost-effective. Health care
      professionals have an important role in shaping their patients' attitudes.
      Patients need more information from their physicians about the risks and benefits
      of estrogen therapy.

PMID- 7573296
TI  - Estrogen replacement therapy in practice: trends and issues.
AB  - Since their availability in 1926, estrogens and their use in postmenopausal women
      have met with both acceptance and alarm by the medical profession and potential
      estrogen users. It was not until the 1980s that long-term research began to
      demonstrate the beneficial effects of estrogen, thus contributing to a
      significant increase in use during the past decade. This article provides
      information on current use of estrogen replacement therapy and describes factors
      influencing continuance. Poor continuance remains a barrier to the full potential
      of estrogen replacement therapy for postmenopausal women. The role of the
      physician in improving continuance is discussed.

PMID- 7573297
TI  - Emerging delivery systems for estrogen replacement: aspects of transdermal and
      oral delivery.
AB  - The ideal preparation for estrogen replacement therapy has been the object of
      intensive research for decades, and the search continues. More than 40 new
      products are in development in the United States, the United Kingdom, and Europe.
      Most are transdermal, which reflects the growing acceptance of patch technology
      at a time when the overwhelming majority of women who use estrogen replacement
      take oral formulations. Most of the new oral formulations are a combination of
      estrogen and progestin. Aspects of transdermal and oral estrogen are discussed,
      including the advantages and disadvantages for use in women with concomitant
      medical conditions.

PMID- 7573298
TI  - Clinical experience with a seven-day estradiol transdermal system for estrogen
      replacement therapy.
AB  - OBJECTIVE: To describe the efficacy, safety, and wearability of estrogen
      replacement therapy of a 7-day estradiol transdermal system (Climara), developed
      using new drug-in-adhesive technology. STUDY DESIGN: The pharmacokinetics of the
      7-day system were investigated in single- and multiple-dose studies, a relative
      bioavailability study of the two patch sizes, and comparative studies with the
      twice-weekly transdermal system (Estraderm). Safety and efficacy in the treatment
      of vasomotor symptoms compared with conjugated equine estrogens (Premarin) and
      placebo were evaluated in two 11-week, randomized, double-blind, multicenter
      trials in 603 women; the data are combined in this report. Irritation and
      adhesion were also evaluated in comparative studies with Estraderm, Micropore (an
      inert once-weekly tape), and placebo controls. RESULTS: Blood levels were
      sustained for the full 7 days of patch wear, there was no drug accumulation, and
      a physiologic estrone to estradiol ratio was maintained. Pharmacokinetics studies
      showed dose proportionality of the 0.05 and 0.1 mg/day patches. Both patch sizes
      significantly decreased the frequency of hot flushes compared with placebo and
      were comparable with conjugated equine estrogens. There was a statistically
      significant difference between the two patch sizes. The mean overall decline in
      the hot flush rate was 74.6% for the 0.1 mg patch versus 64.5% for the 0.05 mg
      patch (p < or = 0.05). The combined data also showed that the onset of efficacy
      is within 1 to 2 weeks after the start of therapy and that efficacy is fully
      sustained during the 7-day patch wear period with some diminution of effect
      during the treatment-free week of each cycle. Treatment was well tolerated.
      Adverse events led to withdrawal from the studies in 8.9% of subjects. In most of
      these (6.8% of subjects), the cause was adverse skin reactions. Skin irritation
      was similar to Estraderm in comparative studies, whereas adhesion was
      significantly better with Climara. CONCLUSION: The Climara patch delivers
      estradiol for a full 7 days. Clinical efficacy of both patch sizes is comparable
      with currently accepted therapy and is sustained for the entire week of patch
      wear. A significant difference in response between the two doses supports dose
      titration. The patch is well tolerated and has excellent adhesion.

PMID- 7573299
TI  - Short-term efficacy of apraclonidine hydrochloride added to maximum-tolerated
      medical therapy for glaucoma. Apraclonidine Maximum-Tolerated Medical Therapy
      Study Group.
AB  - PURPOSE: We determined whether the addition of topical apraclonidine
      hydrochloride to eyes that are receiving maximal medical therapy but still have
      inadequate intraocular pressure control and that are scheduled to undergo surgery
      could adequately decrease intraocular pressure, postponing the need for further
      intervention. METHODS: We performed a prospective, 90-day, multicentered, placebo
      controlled, double-masked parallel study. We enrolled one eye each of 174
      glaucoma patients with inadequate intraocular pressure control who were on
      maximally tolerated medical therapy. We continued to administer maximum medical
      therapy for glaucoma. Study medications were either apraclonidine hydrochloride
      0.5% or placebo (apraclonidine's vehicle). Patients were instructed to take the
      study medication every eight hours. We measured intraocular pressure, change in
      intraocular pressure from baseline, and the number of eyes requiring surgery
      after the addition of study medication. RESULTS: Fifty-two (60%) of 86 patients
      treated with apraclonidine maintained adequate intraocular pressure control
      throughout the study and avoided surgery, compared with 28 (32%) of 88 patients
      treated with placebo (P < .001). Apraclonidine treatment resulted in
      significantly more patients attaining an additional 20% reduction or more in
      intraocular pressure from baseline and an intraocular pressure less than or equal
      to 20 mm Hg (P < .05). The most common ocular complication was conjunctival
      hyperemia (11 of 86 patients, 12.8%). The most frequent nonocular problem was dry
      mouth (four patients, 4.7%). CONCLUSION: Apraclonidine appeared to be safe in all
      eyes and efficacious in some eyes. It significantly lowered intraocular pressure
      when used in combination with maximally tolerated medical therapy, which delayed
      or prevented further glaucoma surgery for at least 90 days in 52 (60%) of 86
      treated patients.

PMID- 7573301
TI  - Optic nerve vasomotor effects of topical beta-adrenergic antagonists in rabbits.
AB  - PURPOSE: To examine the anterior optic nerve vasomotor effects of nonselective
      and relatively beta-1-selective beta-adrenergic antagonists in rabbits, because
      different influences on optic nerve blood flow with these medications have been
      suggested. METHODS: After topical therapy for 30 days with either timolol maleate
      0.5% (six rabbits), betaxolol hydrochloride 0.5% (six rabbits), or placebo (two
      rabbits), the microvasculature of the optic nerve was examined with an
      intraluminal microvascular corrosion casting technique. The investigators were
      masked to both the medication group and the treated eye. The constriction, in
      percent of the downstream vessel caliber, was measured at the vascular branching
      point of arterioles supplying the anterior optic nerve. An average constriction
      was calculated and compared between the medication groups and between the treated
      and the contralateral, untreated eyes. RESULTS: Constriction values from a total
      of 218 arterioles supplying the anterior optic nerve were obtained for the 14
      rabbits. The means of the average constriction on the treated side were
      comparable between the groups treated with timolol maleate, betaxolol
      hydrochloride, and placebo (one-way analysis of variance, P = .64), as well as
      between the treated and untreated eyes (two-tailed t-test for paired variables, P
      = .68 for timolol maleate and P = .42 for betaxolol hydrochloride). The
      statistical power to find a difference of 5% or more average constriction was at
      least 90%. CONCLUSIONS: Both relatively selective and nonselective beta
      adrenergic antagonists produce no observable optic nerve vasomotor effects in the
      rabbit eye.

PMID- 7573300
TI  - Regional test-retest variability of confocal scanning laser tomography.
AB  - PURPOSE: To determine the regional differences in the test-retest variability of
      topographic measurements of the optic nerve head obtained with a confocal
      scanning laser retina tomograph. METHODS: Three 10-degree topographic images
      centered on the optic disk of 20 individuals (20 eyes), five normal subjects,
      seven glaucoma suspects, and eight glaucoma patients, were acquired and averaged.
      For each eye, the standard deviation of the mean height at each pixel was
      calculated from the three images and displayed as a gray scale map, which
      represents regional test-retest variability. The standard deviation of the mean
      height of the eight surrounding pixels of each pixel was calculated and plotted
      as a gray scale map, which represents regional steepness. RESULTS: The
      variability maps and steepness maps showed close correspondence in all eyes.
      Regions of high steepness had high variability (r = .31; P < .001). The average
      variability in relatively flat areas (sixth to 15th percentiles for steepness)
      was 19 microns, whereas steeper areas (81st to 95th percentiles for steepness)
      had an average variability of 37 microns. The overall mean variability was 28 +/-
      7 microns. CONCLUSIONS: The regional variability of topographic measurements made
      with the confocal scanning laser tomograph correlates with the steepness of the
      corresponding region and is highest at the edge of the optic disk cup and along
      vessels. Because of their high test-retest variability, these steep areas may not
      be the best locations to follow up patients for progressive glaucomatous damage.

PMID- 7573302
TI  - Posterior amorphous corneal dysgenesis.
AB  - PURPOSE: Posterior amorphous corneal dysgenesis is a rare disorder previously
      described in only four families. We expanded the spectrum of findings and updated
      the classification by adding seven additional cases. METHODS: Three index cases
      were identified during ophthalmic examination at the El Maghraby Eye Hospital and
      Eye Center in Jeddah, Saudi Arabia. We examined all available members of three
      families of different ethnic origin (Saudi Arabian, Egyptian, and Indian) and
      found seven cases of affected patients. Videokeratography and slit-lamp
      photomicrography were done in selected cases. RESULTS: In all seven cases, the
      corneas showed bilateral, diffuse, sheetlike opacities in the posterior stroma,
      with extension to the corneoscleral limbus, and corneal thinning in the more
      severely affected eyes. The clinical findings included variations in corneal
      thickness noted by slit-lamp microscopy and ultrasonic pachymetry, cornea plana,
      marked corneal astigmatism, and progressive ectasia of the cornea. CONCLUSIONS:
      Posterior amorphous corneal dysgenesis is characterized by gray sheetlike
      opacities in the posterior stroma. It occurs in many ethnic groups and exhibits a
      varied spectrum of clinical findings, including iridocorneal adhesions and cornea
      plana. We think the anatomic abnormalities of the cornea warrant classification
      as a corneal dysgenesis rather than as a dystrophy. Longitudinal studies of
      individual eyes and investigation of associated abnormalities in other pedigrees
      may help resolve this distinction.

PMID- 7573304
TI  - Reduced vision secondary to pigmented cellular membranes on silicone intraocular
      lenses.
AB  - PURPOSE: Visually significant, pigmented cellular membranes may form on
      intraocular lenses after implantation. We studied a series of patients to
      determine the onset, visual significance, treatment, and recurrent nature of
      these pigmented membranes in patients who underwent surgery with silicone lens
      implantation. METHODS: In nine eyes (eight patients) with visually significant
      pigmented cellular membranes on their Allergan Medical Optics (Irvine,
      California) silicone intraocular lenses (model SI18NGB or SI26NB), eight
      underwent combined phacoemulsification, intraocular lens implantation, and
      trabeculectomy; one underwent phacoemulsification and lens implantation only. We
      reviewed medical records to identify preoperative, operative, and postoperative
      similarities and differences in care. Clinical examinations and slit-lamp
      photographs, over an average of 21.3 +/- 7.2 months (range, 11 to 31 months),
      documented the effects of different treatment modalities. RESULTS: The patients
      sought treatment ten to 20 weeks (mean, 15 weeks) postoperatively. Except for the
      cellular membranes, each eye was without evidence of inflammation or cystoid
      macular edema. Subjective complaints decreased, and best-corrected Snellen visual
      acuity improved with topical corticosteroid therapy alone. Pretreatment best
      corrected visual acuities ranged from 20/40 to 20/400 (mean, 20/70 using Snellen
      fractions) and improved two to eight (mean, five) Snellen lines, to a range of
      20/20 to 20/50 (mean, 20/25). All nine eyes had recurrence of the membranes after
      treatment terminated and required a maintenance regimen of corticosteroid
      eyedrops. CONCLUSION: The pigmented cellular membranes observed on these silicone
      lenses were visually significant to each patient. The membranes resolved and
      visual acuity improved with topical corticosteroid treatment alone but recurred
      in all patients on cessation of treatment.

PMID- 7573303
TI  - Relationship of familial prominent corneal nerves and lesions of the tongue
      resembling neuromas to multiple endocrine neoplasia type 2B.
AB  - PURPOSE: We studied a two-generation family with an inherited syndrome of
      prominent corneal nerves and lesions of the tongue resembling neuromas without
      the characteristic neoplasms of the multiple endocrine neoplasia type 2B
      syndrome. Several different point mutations in the RET proto-oncogene on
      chromosome 10 have been associated with the multiple endocrine neoplasia type 2
      syndromes. Molecular genetic studies of families with partial phenotypic
      expression of these syndromes may aid in further understanding the origin of the
      variety of clinical manifestations observed in multiple endocrine neoplasia type
      2. METHODS: A family consisting of an 8-year-old male proband, his 10-year-old
      sister, and 40-year-old mother was identified as having prominent corneal nerves
      and lesions of the tongue resembling neuromas. Pentagastrin-stimulated serum
      calcitonin levels were measured in the mother and sister. Molecular genetic
      studies were performed on all three affected members, to look for the specific
      point mutation seen in over 95% of patients with multiple endocrine neoplasia
      type 2B. RESULTS: Serum calcitonin levels were normal, indicating no C-cell
      hyperplasia or medullary thyroid carcinoma. Molecular genetic studies on these
      individuals did not disclose the specific point mutation seen in multiple
      endocrine neoplasia type 2B. CONCLUSIONS: This family demonstrates some of the
      phenotypic features of the multiple endocrine neoplasia type 2B syndrome without
      the characteristic neoplasms or the mutation in the RET proto-oncogene associated
      with multiple endocrine neoplasia type 2B. Their physical findings may be caused
      by genetic alterations within the RET proto-oncogene on chromosome 10 at yet
      undetermined sites.

PMID- 7573306
TI  - Macular epiretinal membrane formation and treated retinal breaks.
AB  - PURPOSE: We sought to determine the incidence of macular epiretinal membrane
      formation in eyes treated for retinal breaks after three different modalities of
      treatment: laser photocoagulation, cryotherapy, or both. METHODS: We reviewed the
      charts of 262 consecutive patients with a diagnosis of retinal tears and included
      205 patients who had more than six months of follow-up. RESULTS: One hundred
      ninety-five patients were treated. One hundred seventy of these patients had
      retinal breaks in one eye and 25 patients had breaks in both eyes, for a total of
      220 treated eyes. Cryopexy was applied in 125 eyes, laser retinopexy in 73 eyes,
      and both modalities in 22 eyes. Macular epiretinal membranes developed in a total
      of 26 eyes: 12 in the cryopexy group, ten in the laser-treated group, and four in
      the dual modality group. No statistically significant difference, at a level of P
      < or = .01, was seen in the rate of epiretinal membrane formation between the
      different treatment modalities. No statistically significant difference, at a
      level of P < or = .01, was seen in the rate of epiretinal membrane formation in
      the presence or absence of vitreous hemorrhage or in the type of precedent
      retinal break. CONCLUSIONS: After treatment of retinal breaks with laser
      photocoagulation and cryotherapy, no statistically significant difference in the
      incidence of macular epiretinal membrane formation was demonstrated.

PMID- 7573305
TI  - Improved surgical treatment of familial exudative vitreoretinopathy in children.
AB  - PURPOSE: To evaluate current surgical results in patients with familial exudative
      vitreoretinopathy and study the histologic findings of epiretinal membranes
      obtained at the time of surgery. METHODS: We performed phakic pars plana
      vitrectomy and membrane peeling on five patients (six eyes) with familial
      exudative vitreoretinopathy, who ranged in age from 18 months to 9 years and had
      traction retinal detachment. Membranes from two eyes (two patients) were analyzed
      by light and electron microscopy. RESULTS: The macula was reattached in all six
      eyes. Visual acuity improved after surgery in five of the six eyes, with two eyes
      improving from a preoperative visual acuity of 20/400 to a postoperative visual
      acuity of 20/25 and 20/60. Electron microscopic analysis of the membranes from
      two patients disclosed thick fibrocellular fragments with vascular elements and
      astrocytes. CONCLUSION: With current surgical techniques, there appears to be
      improvement in the anatomic reattachment rate and visual outcome in patients with
      familial exudative vitreoretinopathy. Amblyopia, reproliferation, and vitreous
      hemorrhage may limit long-term improvement in vision.

PMID- 7573308
TI  - Angiographic features and outcome of questionable recurrent choroidal
      neovascularization.
AB  - PURPOSE: We sought to identify specific fluorescein angiographic patterns that
      may have led to the diagnosis of questionable recurrent choroidal
      neovascularization. We evaluated follow-up information to determine whether any
      specific angiographic patterns could be used to identify patients at high risk
      for definite recurrence. METHODS: We identified fluorescein angiograms graded as
      questionable for recurrent choroidal neovascularization that were taken from a
      previous prospective study involving 401 consecutive follow-up visits of patients
      treated with photocoagulation for choroidal neovascularization. We reviewed these
      angiograms to identify specific angiographic patterns that might have led to the
      classification of questionable recurrent choroidal neovascularization. Angiograms
      from visits subsequent to a questionable recurrence were reviewed to determine
      which patterns, if any, were associated with an increased risk for a definite
      recurrence to develop later. RESULTS: Forty-four eyes (44 patients) with
      questionable recurrences (of which 40 had at least four months of follow-up) were
      categorized into six angiographic patterns. The three most common patterns
      included the following: (1) focal staining along the edge of the laser lesion (20
      cases, 15 subsequently recurred); (2) blocked fluorescence from subretinal
      hemorrhage not documented at the previous visit (eight cases, five subsequently
      recurred); (3) speckled hyperfluorescence noted beyond the edge of the laser
      lesion (eight cases, six subsequently recurred). CONCLUSIONS: Questionable
      recurrent choroidal neovascularization may be identified by specific angiographic
      patterns. Focal staining along the edge of the laser lesion and speckled
      hyperfluorescence were the patterns that were most likely to progress to definite
      recurrence.

PMID- 7573307
TI  - Tractional elevation of Henle's fiber layer in idiopathic macular holes.
AB  - PURPOSE: We sought to clarify the morphologic features of macular hole
      development. METHODS: Using scanning laser ophthalmoscopy, we examined 47 eyes
      with macular holes before and after vitrectomy. Cases included three eyes with
      stage 1B disease (foveal detachment), 14 with stage 2 (break at the fovea), 21
      with stage 3 (full-thickness macular hole), and nine with stage 4 (detached
      operculum), according to Gass's classification. Ten eyes with central serous
      chorioretinopathy served as controls. RESULTS: Radiating striae of Henle's fibers
      were seen around the elevated rim of the macular cyst or hole when the
      intraretinal structures were illuminated by helium-neon laser. Granularity was
      observed on the macular hole floor. A granular reflex corresponding to the
      macular break or hole, but no radiating striae were seen by argon blue laser. In
      40 eyes in which macular holes were successfully closed by vitrectomy, radiating
      striae of Henle's fiber layer disappeared, and the normal foveal depression was
      restored. The ten eyes with central serous chorioretinopathy had a normal
      foveolar depression and no detectable radiating striae of Henle's fiber layer,
      despite full-thickness retinal detachment in the macular area. CONCLUSIONS:
      Tractional elevation of Henle's fiber layer with intraretinal foveolar cyst
      formation is the initial feature of macular hole development. A macular hole is
      formed when the anterior cyst wall containing Henle's fiber layer is operculated.
      Remnants of the photoreceptor cell layer remain on the hole floor in the early
      stage of macular hole development and subsequently degenerate.

PMID- 7573309
TI  - Single-dose compared with fractionated-dose radiation of the OM431 choroidal
      melanoma cell line.
AB  - PURPOSE: To compare single-dose and fractionated-dose radiotherapeutic effects on
      choroidal melanoma cells. METHODS: We determined the effects of gamma radiation
      on OM431 cell survival by exposing cells to either a single 9-Gy dose or two 4.5
      Gy fractionated doses at intervals of 20 minutes to eight hours. The effects of
      single dosing and fractionated dosing at six hours were compared at doses of 2 to
      12 Gy. RESULTS: Tumor cell repair was most rapid during the first two hours.
      Maximum repair had occurred by six hours after radiation. Cell survival curves
      showed doses greater than 3 Gy of single-dose gamma radiation resulted in a
      greater number of cells killed than did equivalent fractionated doses.
      CONCLUSIONS: Ocular melanoma in vitro is relatively radioresistant to low-dose
      fractionated radiotherapy. High single-dose radiotherapy would be more effective
      but would also result in more damage to normal tissue unless more focused
      modalities of radiotherapy are used.

PMID- 7573312
TI  - Authors interactive: AJO on the Internet.

PMID- 7573313
TI  - Eye care in a managed care environment.

PMID- 7573311
TI  - Prevalence of palpebral fissure asymmetry in white persons.
AB  - PURPOSE: Because palpebral fissure asymmetry in horizontal gaze is reportedly
      common in otherwise normal persons, we determined the prevalence of physiologic
      palpebral fissure asymmetry for primary and horizontal gazes. METHODS: We
      measured the palpebral fissure height of both eyes of 88 healthy white subjects.
      Measurements were obtained with high-resolution videography, with the eyes in
      primary position, in 45-degree right gaze, and in 45-degree left gaze. RESULTS:
      Of the 88 subjects, 36 (41%) were male and 52 (59%) were female. The ages ranged
      from 12 to 50 years, with a mean of 32.5 +/- 9.0 years. When a criterion of equal
      to or greater than 1 mm was used, the prevalence of physiologic palpebral fissure
      asymmetry was 5.7% (five of 88) in primary gaze, 18.2% (16 of 88) in right gaze,
      and 14.8% (13 of 88) in left gaze. The largest observed palpebral fissure
      asymmetry was 2.1 mm. After correcting for any existing fissure asymmetry in
      primary gaze, two-tailed trivariate analysis of variance showed that the fissure
      of the adducting eye tended to be wider. The mean increase in the palpebral
      fissure of the adducting eye was 0.12 mm for right gaze (P = .052) and 0.13 mm
      for left gaze (P = .034). Additionally, a chi 2 test indicated that the
      occurrence of wider adducting eye in both right and left gazes was highly
      significant (P = .0023). CONCLUSIONS: In this sample of white subjects, palpebral
      fissure height asymmetry increased in horizontal gaze to the right and to the
      left, which is in part because of a tendency of the adducting eye to widen
      slightly. In contrast to previous reports, the prevalence of palpebral fissure
      asymmetry was low, and the abducting eye did not widen significantly.

PMID- 7573310
TI  - The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota.
AB  - PURPOSE: To determine the incidence of Graves' ophthalmopathy. METHODS: A
      population-based cohort of all Olmsted County, Minnesota, residents who had
      ophthalmopathy associated with autoimmune thyroid disease between Jan. 1, 1976,
      and Dec. 31, 1990, was identified through the medical diagnostic index of the
      Mayo Clinic and the Rochester Epidemiology Project. RESULTS: One hundred twenty
      incident patients were identified, of whom 103 (85.8%) were women (P = .00001;
      normal relative deviate test). The overall age-adjusted incidence rate for women
      was 16.0 cases per 100,000 population per year, whereas the rate for men was 2.9
      cases per 100,000 population per year (standardized rate ratio, 5.5; 95%
      confidence interval, 3.3 to 9.3). The distribution of incidence rates by five
      year age groups included peak incidence rates in the age groups 40 to 44 years
      and 60 to 64 years in women, and 45 to 49 years and 65 to 69 years in men.
      CONCLUSIONS: Incidence rates for Graves' ophthalmopathy exhibited an apparent
      bimodal peak for both men and women, although the peaks for men occurred
      approximately five years after those for women. No explanation for these trends
      was apparent from the data collected.

PMID- 7573314
TI  - A scleral tunnel incision for trabeculectomy.
AB  - PURPOSE: We used a modified technique to construct the trabeculectomy flap.
      METHODS: The technique involved the creation of a scleral tunnel as is used in
      phacoemulsification surgery for cataract. RESULTS: We have used this technique in
      our most recent 90 cases. We believe it is an easier technique to perform than
      conventional flap dissection, and that it yields improved flap construction.
      CONCLUSIONS: The scleral tunnel flap technique offers a number of advantages over
      standard flap construction in trabeculectomy surgery.

PMID- 7573316
TI  - Corneal light scattering after laser in situ keratomileusis and photorefractive
      keratectomy.
AB  - PURPOSE: To compare corneal light scattering after laser in situ keratomileusis
      and photorefractive keratectomy in rabbit eyes. METHODS: For laser in situ
      keratomileusis, a 5-mm, -10-diopter spherorefractive resection was performed on
      the stromal bed under a corneal flap. Corneal light scattering was objectively
      measured for 12 weeks, and compared to corneal light scattering after
      photorefractive keratectomy (5 mm, -10 diopters). RESULTS: Corneal light
      scattering was significantly lower in the laser in situ keratomileusis group than
      in the photorefractive keratectomy group at all time points after surgery (P <
      .01 at weeks 1 through 6, and P = .03 at week 12). CONCLUSIONS: In this
      experimental study, laser in situ keratomileusis resulted in significantly less
      corneal light scattering than photorefractive keratectomy.

PMID- 7573315
TI  - Lichen planus associated with topical beta-blocker therapy.
AB  - PURPOSE: We studied two clinical cases that demonstrated an association between
      topical beta-blocker therapy and lichen planus. METHODS: Two patients developed
      skin lesions while on topical beta-blocker therapy for open-angle glaucoma. They
      underwent skin biopsies to determine the origin of the lesions. They were
      subsequently treated and followed up clinically. RESULTS: Skin biopsy specimens
      from each patient demonstrated infiltrates consistent with a lichenoid drug
      reaction. The symptoms resolved after discontinuation of the topical beta-blocker
      therapy. Neither patient developed a recurrence. CONCLUSION: We suggest that
      lichen planus is a possible side effect of topical beta-blocker therapy.

PMID- 7573317
TI  - Aspergillus endophthalmitis after sutureless cataract surgery.
AB  - PURPOSE: We studied a case of Aspergillus endophthalmitis after sutureless
      cataract surgery. METHODS: A patient underwent sutureless phacoemulsification
      complicated by a posterior capsular tear. She subsequently developed Aspergillus
      endophthalmitis. Amphotericin B was injected intravitreally at the time of repeat
      pars plana vitrectomy. RESULTS: The eye was enucleated because of pain and poor
      response to treatment. CONCLUSIONS: We recommend suturing the wound in any eye
      that has experienced a complication of surgery.

PMID- 7573322
TI  - Atypical Peters' anomaly associated with partial trisomy 5p.
AB  - PURPOSE: We examined a child who had atypical Peters' anomaly and partial trisomy
      5p. METHODS: An 11-week-old female infant with multiple developmental
      malformations and a partial trisomy 5p had bilateral corneal opacities extending
      from the center of the cornea to the paralimbal region and bilateral iridocorneal
      adhesions in the areas of the corneal opacities. RESULTS: In addition to
      association with several other chromosomal disorders, Peters' anomaly may be
      associated with partial trisomy 5p. CONCLUSIONS: Since partial trisomy 5p can be
      diagnosed by genetic evaluation, a chromosomal analysis should be performed for
      children with Peters' anomaly.

PMID- 7573318
TI  - Cardiopulmonary arrest after retrobulbar anesthesia in a patient with an orbital
      roof defect.
AB  - PURPOSE: Cardiopulmonary arrest developed after injection of bupivacaine
      hydrochloride, lidocaine, and hyaluronidase in a 78-year-old woman who had
      previously undergone ipsilateral transcranial orbital surgery with removal of the
      bone of the orbital roof. METHODS: The patient required immediate cardiopulmonary
      resuscitation and intubation. Mechanical ventilation was necessary for 18 hours
      before spontaneous respirations resumed. RESULTS: The patient improved and was
      discharged on the fifth postanesthetic day. CONCLUSIONS: There were several
      possible mechanisms by which the local anesthetic could have entered the central
      nervous system. In patients with orbital roof defects, we recommend that
      retrobulbar anesthetic agents be used with caution.

PMID- 7573319
TI  - Bone wax template for the correction of enophthalmos with porous polyethylene
      implants.
AB  - PURPOSE: We used a technique that facilitates the custom contouring of porous
      polyethylene implants. METHODS: Bone was was molded in the subperiosteal space of
      the orbit. The wax then served as a model for free-hand sculpting of the rigid
      implant. RESULTS: Bone wax templates have been used successfully in seven
      patients with enophthalmos or superior sulcus depression. CONCLUSIONS: This
      technique has increased the precision of custom contouring subperiosteal
      alloplastic implants.

PMID- 7573321
TI  - Limbal and choroidal Cryptococcus infection in the acquired immunodeficiency
      syndrome.
AB  - PURPOSE: A 30-year-old patient with the acquired immunodeficiency syndrome (AIDS)
      had limbal nodules and multifocal choroidal lesions. METHODS: A biopsy of the
      limbal nodules was performed. RESULTS: The biopsy showed Cryptococcus neoformans
      surrounded by thick mucinous capsules without inflammatory cell infiltration.
      CONCLUSION: In the differential diagnosis of limbal mass in patients with AIDS,
      cryptococcal infection should be considered.

PMID- 7573320
TI  - Scleritis, uveitis, and glaucoma in a patient with rheumatic fever.
AB  - PURPOSE: To determine the origin of scleritis, uveitis, and glaucoma in a boy
      with fever, sore throat, joint pains, and malaise. METHODS: The patient underwent
      extensive hematologic, serologic, rheumatologic, and radiologic examinations.
      RESULTS: The patient recovered after extensive medical therapy. He met the Jones
      criteria for the diagnosis of acute rheumatic fever and had an increased result
      for antistreptolysin O antibody titer. CONCLUSIONS: Antistreptococcal antibody
      testing is helpful in diagnosing rheumatic fever as a cause of scleritis,
      uveitis, and glaucoma.

PMID- 7573324
TI  - Intellectual rigor and correspondence regarding brief reports.

PMID- 7573325
TI  - Corneal lipidosis in patients with the acquired immunodeficiency syndrome.

PMID- 7573323
TI  - High-pressure directed water jets as a cause of severe bilateral intraocular
      injuries.
AB  - PURPOSE: To draw attention to the characteristic features of eye injuries caused
      by high-pressure water jets. METHOD: We examined three patients with bilateral
      eye injuries caused by directed high-pressure water jets. RESULTS: All three
      patients had reduced visual acuity bilaterally, extensive eyelid ecchymosis,
      subconjunctival hemorrhages, hyphema, iris sphincter rupture, transient increase
      in intraocular pressure, and inferior commotio retinae. These injuries were
      confined primarily to the lower parts of the eyes. CONCLUSIONS: High-pressure
      water jets may cause bilateral eye injuries affecting primarily the anterior and
      inferior parts of the eyes. Because of concern about late effects of injuries,
      long-term follow-up is recommended.

PMID- 7573326
TI  - Clinical analysis of excimer laser photorefractive keratectomy using a multiple
      zone technique for severe myopia.

PMID- 7573327
TI  - Clinical correlation of ultrasonographic findings in macular holes.

PMID- 7573328
TI  - Intraoperative fibrinolysis of submacular hemorrhage with tissue plasminogen
      activator and surgical drainage.

PMID- 7573329
TI  - An exploratory study of how occupational therapists develop therapeutic
      relationships with family caregivers.
AB  - Family members, who provide 70% to 80% of all long-term care, have often been
      perceived by occupational therapists as a barrier to, rather than a partner in,
      effective care for elderly persons. This perception suggests that in order to
      build effective partnerships to manage complex issues, occupational therapists
      working with elderly persons must develop effective strategies for involving
      family members in the therapeutic process. This article describes a pilot study
      that examined how occupational therapists engage family caregivers of elderly
      persons receiving home care services. A qualitative descriptive approach was used
      to explore the behaviors demonstrated by two occupational therapists when working
      with family caregivers. The findings point to four primary types of occupational
      therapist-caregiver interaction, categorized as: caring, partnering, informing,
      and directing. These interaction styles were compared with current literature
      describing state-of-the-art occupational therapy practices with older adults and
      family caregivers. An emphasis was placed on examining how therapeutic
      interactions can evoke different caregiver responses and influence the
      development and maintenance of collaborative therapeutic relationships. The
      results of this pilot study can serve as a framework for further exploration of
      interactive strategies that promote caregiver empowerment and ultimately
      influence the ability of families to assume responsibility for the long-term care
      required by many chronically disabled older adults.

PMID- 7573330
TI  - Innovation and leadership in a mental health facility.
AB  - For 3 1/2 years an occupational therapist persevered in efforts to introduce an
      innovative outpatient service of multidisciplinary team case management within a
      general community hospital. The service was intended to meet the needs of
      discharged clients with severe mental illnesses who were attempting to live
      successfully and satisfactorily in the community. The reality of attempting to
      initiate change in medical bureaucracies involves ongoing negotiation and
      persuasion, issues of power and politics, differing cultural visions, and
      strongly committed leadership. This case study describes the developmental
      process of innovation and the contribution of occupational therapy philosophy and
      practice to the therapist's emergent leadership in promoting cultural change.
      Some of the lessons to be learned from this case study by others who would
      attempt institutional innovation include articulating a clear vision that uses
      new language, building coalitions, and being flexible and persistent.

PMID- 7573331
TI  - Outcomes of tendon transfer surgery and occupational therapy in a child with
      tetraplegia secondary to spinal cord injury.
AB  - OBJECTIVE: Tendon transfer surgery to augment hand function lost to spinal cord
      injury (SCI) has gained acceptance as a rehabilitation option for adults but has
      yet to be fully explored in children. In this study, hand function and
      performance of activities of daily living in an 11-year-old child with an SCI
      were evaluated before and after surgical transfers of the brachioradialis to the
      flexor pollices longus and the extensor carpi radialis longus to the flexor
      digitorum profundus. METHOD: With the use of a single-subject AB design, repeated
      measures of pinch force, the Jebsen Test of Hand Function for Children and the
      Grasp and Release Test were obtained before tendon transfer surgery and at 2 1/2
      6, and 12 months after surgery. Activities of daily living were assessed with the
      Functional Independence Measure (FIM) and the Common Object Test (COT) before
      surgery and 12 months after surgery. RESULTS: Each assessment revealed a
      significant improvement in hand function after surgery. Pinch force was
      measurable only after tendon transfers and increased throughout the first year.
      By two standard deviation analyses, after surgery there were significantly more
      task completions for all Grasp and Release Test objects, and task completion
      times were shorter for the light and heavy objects of the Jebsen Test of Hand
      Function for Children. FIM results showed that self-catheterization and cutting
      food were possible only after surgery, and results of the COT revealed new
      unilateral and bilateral abilities that facilitated the client's independence in
      writing, eating, applying toothpaste, and brushing teeth. CONCLUSION: This single
      subject study demonstrates the benefits of tendon transfers for active grasp in a
      child with an SCI.

PMID- 7573332
TI  - Developmental dyspraxia by any other name: are they all just clumsy children?
AB  - The recent introduction of the diagnostic category developmental coordination
      disorder (DCD) (American Psychiatric Association [APA], 1987, 1994), has
      generated confusion among researchers and clinicians in many fields, including
      occupational therapy. Although the diagnostic criteria appear to be similar to
      those used to define clumsy children, children with developmental dyspraxia, or
      children with sensory integrative dysfunction, we are left with the question: Are
      children who receive the diagnosis of DCD the same as those who receive the other
      diagnoses, a subgroup, or an entirely distinct group of children? This article
      will examine the theoretical and empirical literature and use the results to
      support the thesis that these terms are not interchangeable and yet are not being
      used in the literature in a way that clearly defines each subgroup of children.
      Clear definitions and characteristic features need to be identified and
      associated with each term to guide occupational therapy assessment and
      intervention and clinical research.

PMID- 7573333
TI  - Factors influencing entry-level occupational therapists' attitudes toward persons
      with disabilities.
AB  - Negative attitudes exhibited by rehabilitation professionals could have adverse
      consequences for persons with disabilities in their achievement of desired
      outcomes. Because occupational therapists are in a position to exert considerable
      influence in the therapeutic relationship, this study explored entry-level
      occupational therapy practitioners' equal status contact with and attitudes
      toward persons with disabilities. METHOD. Questionnaires were sent to 402 entry
      level occupational therapists. These questionnaires consisted of: a demographic
      scale, the Disability Social Distance Scale, the Contact With Disabled Persons
      Scale, and a Similarity Scale (constructed for this study to evaluate the concept
      of equal status). Data analysis explored the relationship between 172
      respondents' equal status perception and contact with persons with disabilities
      and their attitudes toward persons with disabilities. RESULTS. Respondents
      exhibited generally positive attitudes toward persons with disabilities.
      Perceived equality, personal and professional contact, and the majority of
      demographic factors were not significantly correlated with their attitudes toward
      persons with disabilities. Respondents who specified working with persons without
      disabilities in the wellness capacity exhibited more positive attitudes than
      those working with persons with biomechanical and neurological disabilities. In
      addition, respondents who had a greater frequency of professional contact with
      persons with disabilities also appeared to experience more personal contact with
      persons with disabilities. CONCLUSION. Entry-level occupational therapists'
      attitudes toward persons with disabilities may not only be influenced by
      parameters of the contact variable but also by the profession's holistic
      philosophy, the occupational therapy educational curricula, and the personal
      characteristics of those who choose to pursue a career in occupational therapy.

PMID- 7573337
TI  - Adults with traumatic brain injury: three case studies of cognitive
      rehabilitation in the home setting.
AB  - This article discusses the use of occupational therapy in the home setting and
      the individual application of treatment methods. Three case studies are presented
      that involve adults with acquired brain injury with memory deficits. The
      treatment methods used were (a) saturational cuing with behavioral chaining and
      positive reinforcement, (b) a coordinated team approach incorporating family or
      significant others and other therapists, and (c) environmental adaptations. A
      decision-making model and the dynamic assessment approach were used as a
      framework for treatment planning. The treatment technique chosen depended on the
      skill to be learned and the patient's learning style. Each case required the
      selection of environmental adaptations including (a) use of family and attendants
      as cotherapists; (b) a tape-recorded message, played daily; and (c) an
      appointment book for daily things to do. Each case demonstrated prolonged therapy
      for skill acquisition with this patient population.

PMID- 7573335
TI  - The relationships among sensorimotor components, fine motor skill, and functional
      performance in preschool children.
AB  - OBJECTIVES: This correlational study investigated the relationships among
      sensorimotor components, standardized measures of fine motor skill, and
      functional performance in self-care, mobility, and social interaction. It also
      examined which sensorimotor components and fine motor skills were predictors of
      functional performance. METHOD: Thirty preschool children with motor delays were
      evaluated with tests of in-hand manipulation, tactile defensiveness,
      stereognosis, grasping strength, and fine motor skill. Parents of the subjects
      were interviewed with the Pediatric Evaluation of Disabilities Inventory.
      Correlational and regression analyses were computed. RESULTS: Significant
      correlations were found among sensorimotor components and discrete fine motor
      skills as measured on standardized observational tests. Few correlations emerged
      between foundational components of fine motor skill and functional performance in
      self-care, mobility, and social function. CONCLUSION: Lack of significant
      relationships among the variables, all of which were aspects of functional
      performance might be due to the difference between judgment-based and
      observational evaluation, the influence of the environmental context on the
      child's performance, and the influence of cultural values on the opportunities
      afforded to the child.

PMID- 7573334
TI  - Normative data for grip strength of elderly men and women.
AB  - OBJECTIVES: Grip strength is an important prerequisite for good performance of
      the upper limb, hence it is important to evaluate it correctly. However, one of
      the main difficulties in evaluating the grip strength of elderly patients is the
      absence of valid norms. Therefore, the objective of this study was to develop
      normative data for maximum grip strength of persons aged 60 years and older.
      METHOD: The grip strength of 360 subjects aged 60 years and older, randomly
      recruited by age and gender strata, was evaluated with the Jamar dynamometer and
      the Martin vigorimeter according to the protocol of the American Society of Hand
      Therapists. RESULTS: Grip strength diminishes curvilinearly with age, and men are
      consistently stronger than women. The data are presented by the means, standard
      deviations, and range, and as predictive equations obtained by regression
      analysis. In addition to age and gender, hand circumference and body height
      proved to be the best indicators of grip strength for this population of elderly
      subjects. CONCLUSION: The random recruitment of subjects, the high participation
      rate in the study, and the comparability of the subjects who agreed to
      participate and those who refused give this study the high external validity that
      is essential to any norm study. The predictive equations will help occupational
      therapists to better estimate the expected grip strength of elderly patients than
      they could if using only age and gender.

PMID- 7573336
TI  - Clinical interpretation of "the relationships among sensorimotor components, fine
      motor skill, and functional performance in preschool children".

PMID- 7573338
TI  - Sexual orientation: its relevance to occupational science and the practice of
      occupational therapy.
AB  - This article examines how sexual orientation may be relevant to the study of
      occupations and the practice of occupational therapy. It is suggested that a
      lesbian, gay, or bisexual orientation may influence the occupations in which a
      person engages, the symbolic interpretation of those occupations, and the
      environmental contingencies of those occupations, and thus is an appropriate
      topic for occupational scientists to address. With the use of clinical reasoning
      studies and literature on authentic occupational therapy, it is argued that a
      person's lesbian, gay, or bisexual orientation may be relevant to the therapeutic
      process if therapists are to truly achieve an intersubjective understanding of
      the patient's world and create an environment in which the patient is able to
      live a meaningful life. Given this argument as a foundation, the article explores
      why sexual orientation may be overlooked in some of the theoretical perspectives
      that guide practice. The narrative perspective on identity is introduced as one
      potentially valuable way that occupational therapy researchers and practitioners
      may understand sexual orientation and its relationship to occupation.
      Specifically it is suggested that sexual orientation may be understood, in part,
      as a symbolic theme of meaning that informs values and convictions that may then
      be expressed in one's choice of occupations.

PMID- 7573339
TI  - Working memory and older adults: implications for occupational therapy.
AB  - Atkinson and Shiffrin's (1968) modal model of memory is still commonly used by
      rehabilitation professionals to evaluate memory impairment in older adults.
      However, research to date has been unable to indicate that short-term memory
      declines with age. These findings have led some rehabilitation professionals to
      mistakenly conclude that short-term memory is not affected by the aging process.
      This article reviews both the traditional concept of short-term memory, as
      outlined by Atkinson and Shiffrin, and the more recent conceptualization of short
      term memory in terms of Baddeley and Hitch's (1974) model of working memory. The
      implications of the concept of working memory has implications for occupational
      therapy interventions for older adults. For example, clients with dementia may
      experience difficulties in performing tasks that require drawing inferences.
      Similarly, language that contains vague references may present problems for these
      clients. In addition, changes in working memory in older adults suggest that they
      may experience difficulties with medication management and what Rule, Milke, and
      Dobbs (1992) called wayfinding. Therefore, evaluations of working memory would
      provide a better indication of older adults' memory performance than the modal
      model.

PMID- 7573340
TI  - Families who live in chronic poverty: meeting the challenge of family-centered
      services.
AB  - Family-centered occupational therapy services are based on a collaborative
      relationship that does not always come easily. Role performance in parenting a
      child with special needs and being a consumer of occupational therapy services
      can be partially understood in terms of environmental context. Although
      occupational therapists recognize the need to adjust services to the cultural and
      economic backgrounds of families, most of the available literature has examined
      the contribution of ethnic differences. A particular challenge for occupational
      therapists may be treating clients and their families who live in chronic
      poverty. This article examines chronic poverty as it shapes parenting the child
      with special needs and subsequently the caregiver's participation in occupational
      therapy services. A framework for understanding cultural differences is used to
      suggest contrasting value orientations between families who live with persistent
      poverty and occupational therapists. A family-centered approach challenges the
      professional to understand varied influences on caregiving. Suggestions are
      offered to enhance communication between therapists and caregivers.

PMID- 7573341
TI  - Interactive journals: an educational strategy to promote reflection.
AB  - Reflection is an essential component of clinical reasoning in occupational
      therapy practice. The specialty area of mental health practice can elicit
      awareness and introspection for occupational therapy students at personal and
      professional levels. This article, a qualitative case study, describes the use of
      interactive journals in the mental health component of an undergraduate
      occupational therapy curriculum to foster and develop reflective skills. Students
      kept journals and submitted them biweekly; faculty members responded to the
      journals in writing within 24 hr. The journals were analyzed for common themes
      over the length of the course as well as at each biweekly period. Frequent themes
      were students' increased awareness and openness to the specialty area and
      positive changes in attitude associated with new knowledge and experiences. The
      results indicate that interactive journals in academic courses have the potential
      to be an effective strategy to promote reflection.

PMID- 7573343
TI  - Clinical practice guidelines for post-stroke rehabilitation and occupational
      therapy practice.

PMID- 7573342
TI  - A study of the development of traits of entry-level occupational therapy
      students.
AB  - OBJECTIVES: This study compared the personality traits of entry-level
      occupational therapy students before and after their participation in 2 years of
      academic and clinical education in order to examine the change of traits in their
      professional personality profile. METHOD: Forty-nine occupational therapy
      students completed the 18 scales of the California Psychological Inventory during
      their first fall and second spring semesters. This time span included two Level I
      and one Level II fieldwork experiences. RESULTS: T tests were used to analyze the
      students' scales. Students' scores in the second test showed a statistically
      significant increase in 13 of the 18 scales as compared to their first test
      scores. Achievement via independence and psychological-mindedness emerged as the
      highest ranking personality traits of the students in their second test scores.
      CONCLUSION: The occupational therapy curriculum may have influenced the scores of
      the entry-level students, in both intellectual and psychosocial traits, in a
      positive direction.

PMID- 7573345
TI  - Communication skills: why not turn to a skills training model?

PMID- 7573344
TI  - The profession's image, 1917-1925, Part I: Occupational therapy as represented in
      the media.
AB  - This first part of a two-part article examines how occupational therapy was
      represented in the media during the formative years of the profession, 1917-1925.
      Through an examination of 44 articles published in The New York Times during
      these years, three common themes emerged: restoration of persons with
      disabilities to social usefulness, the many facets of occupational therapy, and
      achieving public recognition of occupational therapy. This analysis indicates
      that the media portrayed occupational therapy as a small but important profession
      primarily concerned with restoring patients to economic and social usefulness.
      This favorable portrayal was in keeping with the values of the times and may have
      contributed to promoting public acceptance of the profession.

PMID- 7573346
TI  - In vivo expression of monokine and inducible nitric oxide synthase in
      experimentally induced pulmonary granulomatous inflammation. Evidence for
      sequential production of interleukin-1, inducible nitric oxide synthase, and
      tumor necrosis factor.
AB  - The present study examined the temporal pattern and localization of interleukin
      1, tumor necrosis factor-alpha, and inducible nitric oxide synthase expression in
      lung tissue undergoing foreign body granuloma formation. Pulmonary granulomas
      were induced by the intratracheal injection of dextran beads into genetically
      high granuloma responder, carrying Bcgs (BALB/c), and low responder, carrying
      Bcgr (C3H/HeJ and DBA/2), mice. There was a pattern of sequential expression of
      these molecules in BALB/c mice. Thus, interleukin-1 alpha and inducible nitric
      oxide synthase were induced mostly in the cells accumulated around the beads and
      also in some bronchiolar epithelial cells during the early phase (1 to 3 days),
      whereas tumor necrosis factor-alpha was induced in the cells around the beads at
      the later resolution phase (3 to 7 days). By contrast, in low responder mice, an
      increase in the expression of interleukin-1 alpha and inducible nitric oxide
      synthase was detected in lung macrophages as well as in alveolar cells and
      bronchiolar epithelial cells on day 1, but that of tumor necrosis factor-alpha
      was not detected throughout the period. These results together with our previous
      findings on cytokine activity in granuloma extract suggest that interleukin-1 and
      nitric oxide produced by recruited macrophages may take part in the early,
      macrophage-dependent phase of granuloma formation whereas tumor necrosis factor
      alpha may be more crucial as a mediator responsible for the difference in innate
      resistance or susceptibility to granuloma formation.

PMID- 7573347
TI  - Expression and function of galectin-3, a beta-galactoside-binding lectin, in
      human monocytes and macrophages.
AB  - A family of beta-galactoside-binding animal lectins has recently been designated
      as galectins. One member of this family, galectin-3, has been known as epsilon BP
      for its IgE-binding activity and as Mac-2, a macrophage surface antigen, CBP35,
      CBP30, L-29, and L-34. Although much information has accumulated on the
      expression of this lectin in murine macrophages and human monocytic cell lines,
      little is known about the expression and function of this protein in normal human
      monocytes/macrophages. We now report that galectin-3 is expressed in normal human
      peripheral blood monocytes and its level increases dramatically as human
      monocytes differentiate into macrophages upon culturing in vitro. Immunoblot
      analysis showed that there was a 5-fold increase in the level of galectin-3 after
      1 day of culture and greater than a 12-fold increase after 5 days.
      Immunocytochemical analysis confirmed this progressive increase of galectin-3
      expression in cultured monocytes. Immunogold cytochemistry/electron microscopy
      analysis revealed that galectin-3 was expressed on the surface of human monocytes
      and that the level of cell surface galectin-3 increased progressively as these
      cells differentiated into macrophages. The level of galectin-3 in human
      monocytes/macrophages was modulated by stimuli such as lipopolysaccharide and
      interferon-gamma, and galectin-3 was secreted when monocytes were stimulated by
      calcium ionophore A23187 Soluble galectin-3 caused superoxide release from human
      monocytes; this activity was dependent on the lectin property of galectin-3, as
      it was inhibitable by lactose. Thus, galectin-3 may modulate the function of this
      cell type in an autocrine or paracrine fashion through binding to cell surface
      glycoconjugates.

PMID- 7573348
TI  - Procoagulant activity after exposure of monocyte-derived macrophages to minimally
      oxidized low density lipoprotein. Co-localization of tissue factor antigen and
      nascent fibrin fibers at the cell surface.
AB  - The role of tissue factor (TF) as an initiator of the thrombotic complications
      secondary to atherosclerosis has been acknowledged, and in situ expression of TF
      activity by monocyte-derived macrophages and lesion-associated macrophage foam
      cells has been documented. Macrophages express TF activity upon exposure in vitro
      to either oxidized low density lipoprotein LDL (Ox-LDL) or endotoxin
      (lipopolysaccharide). This activity has been associated with membrane vesicles
      that apparently are shed after procoagulant expression. The present study based
      upon the correlative use of an enzyme-linked coagulant assay and three
      dimensional multi-antigen, immunogold electron microscopy, reports the
      ultrastructural localization of TF antigen and spatially correlates TF with OX
      LDL binding and the presence of nascent fibrin polymers on the plasma membrane of
      cultured macrophages. Pigeon monocyte/macrophages, after a 4-hour induction with
      lipopolysaccharide (2 micrograms/ml) or minimally oxidized LDL (50 micrograms/ml;
      thiobarbituric acid reducing substance, 5 to 8 nmol/mg protein) were incubated
      for 40 minutes in a Tris-buffered medium containing factors VII, V, X, II, and I
      before either assaying for coagulant activity or processing for gold-colloid
      cytochemistry. TF activity, as measured by enzyme-linked coagulant assay peaked 6
      hours after agonist exposure with lipopolysaccharide and Ox-LDL giving,
      respectively, 115- and 60-fold stimulation as compared with control. This
      activity corresponded to the elaboration of membrane ruffles and microvilli on
      the cell surfaces. Through correlative immunogold cytochemistry (15-nm-diameter
      colloid) and gold-ligand cytochemistry (30-nm-diameter colloid), TF antigen (83%)
      and Ox-LDL (78%) were primarily associated with the membrane ruffles and
      microvilli. Multi-antigen immunogold cytochemistry when used in conjunction with
      ligand-gold cytochemistry documented co-localization of Ox-LDL (22-nm gold), TF
      antigen (15-nm gold) and a delicate three-dimensional network of short fibrin
      fibers that were decorated in a linear fashion with the immunogold probes (30-nm
      gold). These results provide evidence that TF antigen is located at selected
      regions on the cell surfaces. Furthermore, these same regions provide binding
      sites for agonist uptake and organization sites for fibrin polymerization.
      Hypothetically, the localized membrane regions could be shed from the cell
      surface as a means for regulating coagulation potential.

PMID- 7573349
TI  - Vascular smooth muscle cells from injured rat aortas display elevated matrix
      production associated with transforming growth factor-beta activity.
AB  - The arterial response to injury is characterized by a short period of increased
      proliferation and migration of vascular smooth muscle cells, followed by an
      extended period of extracellular matrix accumulation in the intima. Transforming
      growth factor-beta (TGF-beta) has been implicated as a causative factor in the
      formation of extracellular matrix in this process, which leads to progressive
      thickening of the intima, known as intimal hyperplasia. In vitro analysis of
      vascular smooth muscle cells harvested from normal rat aortas and from aortas
      injured 14 days earlier showed that both types of cells attached equally well to
      culture dishes but that the initial spreading of the cells was increased in cells
      derived from injured vessels. Cells from the injured arteries produced more
      fibronectin and proteoglycans into the culture medium than the cells from normal
      arteries and contained more TGF-beta 1 mRNA. TGF-beta 1 increased proteoglycan
      synthesis by normal smooth muscle cells, and the presence of a neutralizing anti
      TGF-beta 1 antibody reduced proteoglycan synthesis by the cells from injured
      arteries in culture. Fibronectin synthesis was not altered by these treatments.
      These results indicate that the accumulation of extracellular matrix components
      in neointimal lesions is at least partially caused by autocrine TGF-beta activity
      in vascular smooth muscle cells.

PMID- 7573351
TI  - Dynamic redistribution of glycoprotein Ib/IX on surface-activated platelets. A
      second look.
AB  - The present study has re-evaluated the mobility of glycoprotein Ib/IX (GPIb/IX),
      the von Willebrand factor receptor, on surface-activated platelets. A previous
      report employing immunogold cytochemistry with monoclonal and polyclonal
      antibodies specific for GPIb/IX concluded that the receptor remained stabilized
      in plasma membranes and did not move during platelet attachment and spreading on
      formvar grids, despite the observation that immunogold particles marking GPIb/IX
      were missing from peripheral margins and pseudopods of the surface-activated
      platelets. Addition of thrombin to surface-activated, spread platelets freed
      GPIb/IX from its anchor to the membrane and stimulated movement of receptor
      ligand complexes into caps over centers of spread platelets. In our
      investigation, surface-activated platelets, stimulated or not by thrombin, were
      fixed in a higher concentration of glutaraldehyde than used by the earlier
      workers before exposure to monoclonal or polyclonal antibody to GPIb/IX, after
      incubation with the antibody, but before treatment with the immunogold marker,
      protein A gold (PAG), or after both antibody and PAG. When fixed before exposure
      to antibody and PAG, GPIb/IX receptors were dispersed evenly over dendritic and
      spread platelets from edge to edge, including peripheral margins and pseudopods.
      Thrombin had no influence on distribution of the receptors. Exposure to
      antiglycocalicin antibody before fixation caused movement of GPIb/IX receptors
      from peripheral margins of spread cells and pseudopods of dendritic forms.
      Thrombin treatment did not enhance the movement. Fixation after exposure of
      surface-activated platelets, treated or not with thrombin, to antibody and PAG
      caused movement of GPIb/IX receptors into caps over cell centers. Results
      indicate that central movement of GPIb/IX receptors is unrelated to surface
      activation, spreading, or thrombin stimulation. Rather, the translocation is
      caused by the antiglycocalicin antibody and accentuated by PAG.

PMID- 7573350
TI  - Tumor vascularity is not a prognostic factor for malignant melanoma of the skin.
AB  - Tumor vascularity has been proposed as a prognostic indicator for a number of
      solid tumors. Although a correlation between microvessel number and metastatic
      behavior has also been suggested for cutaneous melanoma, the small number of
      cases studied to date allows one to draw only preliminary conclusions. In this
      study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60
      cases of metastasizing and non-metastasizing tumors matched for tumor thickness,
      age, sex, and anatomic site. Ulex europaeus agglutinin I appeared to be the most
      suitable vascular marker for this study. Our results indicate that there was no
      statistically significant difference between the two groups with regard to tumor
      vascularity. Even after identifying 15 cases of thin ( < 1.0 mm thick) melanoma,
      there was no significant difference in the number of microvessels between
      metastasizing and non-metastasizing tumors. Comparison of patterns of vascular
      microarchitecture also failed to discriminate between the two groups. Thus, our
      results indicate that tumor vascularity may not be an independent prognostic
      factor for cutaneous melanoma.

PMID- 7573352
TI  - Expression of thrombospondins by endothelial cells. Injury is correlated with TSP
      1.
AB  - The thrombospondins (TSP-1, -2, and -3) comprise a family of proteins that are
      homologous at the carboxy terminus but have unique sequences at the amino
      terminus that might be correlated with the regulation of cell behavior. To
      investigate the expression of TSP-1, -2, and -3 in endothelial cells, we examined
      developing murine blood vessels and human atherosclerotic plaques by in situ
      hybridization. The expression of TSP-1 was also characterized in cultured bovine
      aortic endothelial cells. Expression of TSP-2 was seen in the dorsal aorta as
      early as embryonic day 10; TSP-1 was not detected in endothelial cells until
      later stages, and TSP-3 was not apparent in the vasculature. In atherosclerotic
      specimens, TSP-1 mRNA was detected in many intraplaque microvessels and in the
      endothelium lining the atheromatous plaque; TSP-2 was absent from these regions.
      Cultured bovine aortic endothelial cells did not transcribe TSP-2 mRNA at
      detectable levels. There were high steady-state levels of TSP-1 mRNA in
      subconfluent bovine aortic endothelial cells before confluence and at the wound
      edge after injury of the cell monolayer, with maximal expression of TSP-1 in
      cultures at a time during which approximately 35% of the cells were in S phase.
      As the majority of these cells subsequently undergo mitosis, these data are
      consistent with TSP-1 as an inhibitor of endothelial cell proliferation that
      functions in G1. These results support the conclusion that, despite sequence
      homology, the TSPs have distinct functions in vascular biology.

PMID- 7573356
TI  - Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor
      suppressor gene in human prostate carcinoma.
AB  - To assess the potential role of ras oncogene activation and p53 tumor suppressor
      gene mutations in the development of human prostate carcinoma, nine cases of
      histologically heterogeneous prostate tumors obtained from total prostatectomies
      were probed for these specific events. Each tumor was divided into 5 to 10 areas
      according to different growth or histological patterns. Targeted DNA sequences
      coding for ras and p53 were amplified by the polymerase chain reaction, analyzed
      by single-strand conformational polymorphisms, and confirmed by direct DNA
      sequencing. Point mutations of the ras gene were found in three of the nine
      tumors. Two contained K-ras codon 13 and H-ras codon 61 mutations, found in only
      one and three areas of each lesion, respectively. The third tumor contained two
      different point mutations in K-ras codons 13 and 61 in different foci of the
      sample. Loss of heterozygosity at the polymorphic codon 72 in the p53 gene was
      detected in two of four informative cases (50%) showing fragment cleavage by
      restriction fragment length polymorphism analysis. Mutations in p53, missense
      transversions, single base insertions, and two base deletions were also detected
      in three tumors. The present results reveal mutated ras and p53 occasionally
      occurring in small foci of the tumor and that genetic mutations in p53, as
      opposed to those in ras, are more closely associated with invasive growth of
      heterogeneous prostate carcinoma.

PMID- 7573355
TI  - Somatic mitochondrial mutation in gastric cancer.
AB  - Likely hot spots for mutations are mitochondrial sequences as there is less
      repair and more damage by carcinogens compared with nuclear sequences. A somatic
      50-bp mitochondrial D-loop deletion was detected in four gastric adenocarcinomas.
      The deletion included the CSB2 region and was flanked by 9-bp direct repeats. The
      deletion was more frequent in adenocarcinomas arising from the gastroesophageal
      junction (4/32, 12.5%) compared with more distal tumors (0/45). Topographical
      analysis revealed the absence of the deletion from normal tissues except in focal
      portions of smooth muscle in one case. In two cases, apparent mutant homoplasmy
      was present throughout two tumors, including their metastases. In the two other
      cases, the mutation was present in only minor focal portions ( < 5%) of their
      primary tumors. These findings document the presence of somatic mitochondrial
      alterations in gastric cancer, which may reflect the environmental and genetic
      influences operative during tumor progression.

PMID- 7573357
TI  - Differential expression of laminin chains and their integrin receptors in human
      gastric mucosa.
AB  - The proliferating cells of the gastric mucosa are found among the pit and mucous
      neck cells. These cells migrate upward to renew the surface epithelium and
      downward to restitute the glandular cells. As the epithelial basement membranes
      (BMs) function as substrate for cell adhesion and migration as well as signals
      for their differentiation, we studied, by indirect immunofluorescence microscopy,
      the distribution of different laminin chains and their integrin receptors in
      adult human stomach. The immunoreactivity for laminin alpha 2 chain localized to
      the BMs of glands and the lower parts of the gastric pits whereas the laminin
      alpha 3 chain (laminin-5/kalinin) immunoreactivity was strictly confined to BMs
      underneath the surface epithelium and the upper parts of the pits. Proliferating
      mucosal epithelial cells, identified by Ki-67 antibodies, were confined to the
      areas containing both alpha 2 and alpha 3 laminin chains. The alpha 1, beta 1,
      and gamma 1 laminin chains were found in all BMs of the mucosa whereas the beta 2
      chain was prominent in mucosal blood vessels and also detectable in some glands.
      Among the laminin integrin receptors, the alpha 3 and beta 4 subunits were seen
      to be expressed in cells along the BMs with the alpha 3 laminin chain. The alpha
      6 integrin, on the other hand, was seen in all gastric epithelia. The present
      results demonstrate that in the adult human stomach laminin alpha 2 and alpha 3
      chains show zonal distribution in BM underlying gastric mucosal epithelium
      whereas other laminin chains show a more general distribution.

PMID- 7573358
TI  - Expression and localization of inducible nitric oxide synthase in anti-Thy-1
      glomerulonephritis.
AB  - To elucidate a possible involvement of nitric oxide in the development of a
      mesangial proliferative glomerulonephritis induced by anti-Thy-1 antibody
      administration, glomerular expression of three isoforms of NO synthase (NOS),
      inducible NOS (iNOS), brain NOS, and endothelial NOS, was examined at both mRNA
      and protein levels by ribonuclease protection assay and immunofluorescence
      microscopy. Light microscopy showed an accumulation of polymorphonuclear
      leukocytes at 1 hour, lysis of mesangial cells at 1 day, a mesangial
      proliferative lesion at 4 to 10 days, and minimal residual glomerular lesions by
      28 days. Ribonuclease protection assay showed that the glomerular expression of
      iNOS mRNA peaked at 1 hour and decreased thereafter. No substantial expression of
      iNOS mRNA was observed in normal glomeruli or in the nephritic glomeruli obtained
      at different time points (1, 4, 10, or 28 days). By immunofluorescence microscopy
      with a specific monoclonal antibody, an intense reaction for iNOS was
      demonstrated in a few cells in the glomeruli at 1 hour. Most of the iNOS-positive
      cells were identified as polymorphonuclear leukocytes. iNOS-positive cells were
      found less frequently in the glomeruli on days 1 and 4. Endothelial NOS mRNA was
      constitutively expressed in normal glomeruli and increased biphasically with two
      peaks at 1 hour and at 4 days or later; however, the peak expression was much
      less than that of iNOS mRNA at 1 hour. Expression of brain NOS mRNA was not
      detectable in either normal or nephritic glomeruli. These results show that iNOS
      is predominantly expressed in polymorphonuclear leukocytes accumulating at 1 hour
      in the glomeruli of anti-Thy-1 glomerulonephritis and suggest an involvement of
      NO in the initiation of the disease.

PMID- 7573353
TI  - Transforming growth factor-alpha promotes mammary tumorigenesis through selective
      survival and growth of secretory epithelial cells.
AB  - Transforming growth factor (TGF)-alpha stimulates the growth and development of
      mammary epithelial cells and is implicated in the pathogenesis of human breast
      cancer. In this report we evaluate the consequences of overexpressing TGF-alpha
      in the mammary gland of transgenic mice and examine associated cellular
      mechanisms. When operating on a FVB/N genetic background (line MT100), TGF-alpha
      induced the stochastic development of mammary adenomas and adenocarcinomas f
      secretory epithelial origin in 64% of multiparous females. In contrast, tumors
      were exceedingly rare in virgin MT100 females, MT100 males, and multiparous FVB/N
      females. In MT100 females multiple foci of hyperplastic secretory lesions
      preceded the development of frank tumors; these initial lesions appeared during
      the involution period after the first lactation. Serial transplantation of these
      hyperplasias indicated an absence of proliferative immortality. Nevertheless,
      they gave rise to tumors at a low frequency and after a prolonged latency in
      virgin hosts; in multiparous hosts, tumors developed earlier and at a high
      incidence. The TGF-alpha transgene was highly expressed in hyperplasias and
      tumors but not in virgin and nonlesion-bearing tissue, suggesting that TGF-alpha
      overexpression provides a selective growth advantage. TGF-alpha also induced at
      lactation a 6.4-fold increase in DNA synthesis in MT100 epithelial cells, many of
      which were binucleated. MT100 mammary tissue experienced an obvious delay in
      involution, resulting in the postlactational survival of a significant population
      of unregressed secretory epithelial cells. In contrast, another line of
      transgenic mice on a CD-1 genetic background (MT42), in which TGF-alpha
      overexpression induced liver but not mammary tumors, failed to demonstrate
      postlactational epithelial cell survival. These data show that TGF-alpha promotes
      mammary tumorigenesis in multiparous MT100 mice by stimulating secretory
      epithelial cell proliferation during lactation and prolonging survival during
      involution. These points support the notion that TGF-alpha can act as a mitogen
      and also as a differentiation factor in mammary epithelium.

PMID- 7573354
TI  - Immunohistochemical and prognostic analysis of apoptosis and proliferation in
      uveal melanoma.
AB  - Neoplasia can be defined as deregulated tissue homeostasis caused by an imbalance
      between proliferation and apoptosis. Many genes are involved in the maintenance
      of tissue homeostasis, eg, the c-myc oncoprotein, which is an important regulator
      of cell proliferation and Bcl-2 protein, which is involved in the regulation of
      apoptosis. We studied retrospectively indices of proliferation, such as mitotic
      count and the Mib-1 index, on 51 uveal melanomas and compared their prognostic
      significance with established indicators of prognosis such as cell type and tumor
      size. Along the same line we investigated the expression of the regulating
      proteins c-myc and Bcl-2. Of all parameters tested, the largest tumor diameter
      and mitotic count were most strongly associated with tumor-related death (P <
      0.001 and P = 0.005, respectively). In addition, cell type, the presence of
      epithelioid cells, the Mib-1 index, and the percentage of cytoplasmic c-myc
      positive cells were significant predictive factors. Multivariate analysis showed
      that the Mib-1 index, largest tumor diameter, and the percentage of cytoplasmic c
      myc-positive cells were independent prognostic parameters. Bcl-2 expression did
      not correlate with clinical outcome. The Mib-1 index correlated with the presence
      of epithelioid cells (P < 0.03) and the presence of apoptotic bodies (P < 0.001)
      and c-myc. A strong inverse relationship was found between (nuclear and
      cytoplasmic) c-myc and Bcl-2 (P < 0.00004 and P < 0.006, respectively),
      suggesting that Bcl-2 cooperates with c-myc to immortalize uveal melanoma cells.

PMID- 7573359
TI  - Lissencephaly gene product. Localization in the central nervous system and loss
      of immunoreactivity in Miller-Dieker syndrome.
AB  - The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by
      deletions of chromosome 17p13.3. Recently, a gene on 17p13.3, named LIS-1, was
      identified as the causative gene for this cerebral anomaly. Here we
      immunochemically and immunohistochemically localized the gene product, LIS-1
      protein, among control normal subjects and patients with Miller-Dieker syndrome,
      using specific antibodies raised against synthetic peptide fragments of LIS-1
      protein. Western blot analyses identified LIS-1 protein as a 45-kd, heparin
      binding protein abundant in the cytosolic fraction. The protein was restricted to
      the central nervous system and detectable in brains of controls of all ages, from
      the early fetal to adult period. Immunostaining demonstrated the widespread
      distribution of LIS-1 protein in the brain and spinal cord of controls and a loss
      of immunoreactivity in individuals with Miller-Dieker syndrome. These results are
      consistent with the notion that a deficiency of LIS-1 protein is the direct cause
      of the brain malformation and that the protein plays a critical role in neuronal
      migration.

PMID- 7573360
TI  - Expression of immune regulatory molecules in Epstein-Barr virus-associated
      nasopharyngeal carcinomas with prominent lymphoid stroma. Evidence for a
      functional interaction between epithelial tumor cells and infiltrating lymphoid
      cells.
AB  - Undifferentiated nasopharyngeal carcinomas (UNPC) are characterized by an
      association with Epstein-Barr virus and an abundant lymphoid stroma. The role of
      this lymphoid stroma is uncertain but is mostly thought to represent an immune
      response against viral or tumor antigens. We have analyzed the expression of
      immune regulatory receptor/ligand pairs in snap-frozen biopsies of 20 UNPCs. All
      cases were Epstein-Barr virus positive and the virus-encoded latent membrane
      protein, LMP1, was expressed in 6 cases. By immunohistochemistry, we have
      demonstrated the expression of CD70 and CD40 in the tumor cells of 16 and 18
      cases, respectively. Infiltrating lymphoid cells expressing CD27, the CD70
      receptor, and the CD40 ligand were present in all cases. The Bcl-2 protein was
      detected in 17 cases. Unexpectedly, tumor cells of 5 cases expressed at least one
      member of the B7 family (CD80, CD86, and B7-3) and many lymphoid cells expressing
      the corresponding counter-receptor, CD28, were detected in all cases.
      Interestingly, 5 of 6 LMP1-positive cases also expressed B7, whereas all 14 LMP1
      negative cases were also B7 negative. Our results indicate that T cells and
      carcinoma cells communicate in the microenvironment of UNPCs and suggest that the
      presence of a lymphoid stroma may be a requirement for UNPC growth at least in
      certain stages of tumor development.

PMID- 7573362
TI  - Between molecules and morphology. Extracellular matrix and creation of vascular
      form.
AB  - In response to an angiogenic stimulus, ECs initiate programs of gene expression
      that result in the quantitative alteration of gene products within nuclear,
      cytoplasmic, cell surface, and extracellular compartments. During the formation
      of new microvasculature, patterns of molecular expression among individual ECs
      must direct the creation of complex, multicellular morphologies in two and three
      dimensions. Studies in vitro indicate that cell-generated forces of tension can
      organize ECM into structures that direct the behavior of single cells (via
      influences on cellular elongation, alignment, and migration) and that provide
      positional information for the creation of multicellular patterns. Significantly,
      the formation of organized matrical structures is controlled by gene products (of
      ECs or other cell types that populate the ECM) that influence the balance between
      the forces of cellular tension and the viscoelastic resistance of the ECM.
      Regulation of relevant genes could be accomplished by soluble molecular signals
      (eg, growth factors) and/or solid-state signals arising from specific
      arrangements of cytoskeletal structure that, in turn, are a function of the
      equilibrium between cellular tension and matrical resistance. Within cells,
      information for the construction of complex organelles is encoded in the shapes
      of the constituent molecules. Similarly, the creation of complex vascular
      architecture must be mediated by molecular shapes, a fact that is readily
      apparent in simple receptor-ligand interactions such as the binding of growth
      factors to ECs or the attachment of ECs to one another. However, between
      molecules and morphology also exists a set of multilayered, interactive,
      multimolecular systems that establish vascular form at unicellular and
      multicellular levels. Characterization of these systems is an elusive target that
      resides at the frontier of vascular biology; the identification of models in
      vitro that accurately reproduce macroscale events of vascular morphogenesis
      should advance considerably our understanding of vascular development and lead to
      an elucidation of its regulation in vivo.

PMID- 7573361
TI  - Expression of cellular adhesion molecules in Langerhans cell histiocytosis and
      normal Langerhans cells.
AB  - Langerhans cell histiocytosis (LCH) is characterized by lesions with an
      accumulation and/or proliferation of Langerhans cells (LCs). Little is known of
      the etiology and pathogenesis of LCH. Although the relation between the LCH cell
      and normal LCs is currently uncertain, the localizations of the LCH cells is
      considered aberrant when compared with normal LCs. Cellular adhesion molecules
      (CAMs) are known to play an important role in a variety of cell functions such as
      migration, antigen presentation, and activation. Aberrant migration of LCs may
      play a role in the pathogenesis of LCH. We investigated CAMs in 27 tissue
      specimens of 20 patients with LCH retrieved from our files during the last 15
      years. LCH cells showed strong expression of CAMs such as CD54, CD58, and the
      beta 1-integrin alpha 4 that are upregulated during activation of normal LCs. In
      contrast, CAMs not found on normal LCs could be demonstrated in a number of cases
      on LCH cells like CD2, CD11a, and CD11b. Also CD62L, normally expressed only by
      epidermal LCs, could be detected on LCH cells. The integrins alpha 5 and alpha 6,
      not or only weakly found on epidermal LCs and highly expressed by activated LCs,
      could not be demonstrated on LCH cells. Our data suggest abnormal expression of
      CAMs on LCH cells that may contribute to abnormal migration of LCs in LCH. The
      aberrant phenotype of LCH cells has characteristics of both epidermal LCs and
      activated LCs and may be indicative of an arrested state of activation and/or
      differentiation of LCs.

PMID- 7573363
TI  - p53-independent expression of the cyclin-dependent kinase inhibitor p21 in
      pancreatic carcinoma.
AB  - The p53 tumor suppressor gene is mutated in the majority of pancreatic
      adenocarcinomas, and several studies have suggested that loss of p53 function may
      contribute to the aggressive clinical behavior of pancreas cancer. Although
      immunocytochemical accumulation of the p53 gene product has previously been
      assessed as a marker for p53 mutations in cancers of the pancreas and other organ
      systems, the relationship between p53 mutations and p53 protein accumulation is
      variable. The cyclin-dependent kinase inhibitor, p21 (also known as WAF1 and
      CIP1), is induced by wild-type but not mutant p53, and recent work has implicated
      p21 as a downstream mediator of the growth-suppressing and apoptosis-promoting
      functions of wild-type p53. In the present work, we sought to determine whether
      loss of p21 expression could more precisely identify those tumors with p53
      mutations and/or loss, compared with immunocytochemical assessment of p53 protein
      accumulation. We evaluated p53 and p21 expression immunohistochemically in a
      series of 21 ductal adenocarcinomas of the pancreas with known p53 mutational
      status. Diffuse overexpression of p53 was found in 3 of 8 cases (38%) with wild
      type p53 and 7 of 13 cases (54%) with p53 mutations with or without loss of
      heterozygosity at 17p. Surprisingly, expression of p21 correlated neither with
      p53 mutational status nor with p53 protein expression. In particular, strong p21
      expression was seen even in carcinomas in which molecular analysis revealed a
      frameshift mutation in one allele of p53 and loss of the second. These data
      suggest that p21 expression in pancreatic adenocarcinoma may also be induced by a
      p53-independent pathway and that p21 expression, as assessed
      immunocytochemically, does not reflect the functional status of p53 in these
      carcinomas.

PMID- 7573364
TI  - Hepatocyte growth factor and Met receptor expression in human pancreatic
      carcinogenesis.
AB  - We have used immunohistochemistry to evaluate the clinicopathological
      significance of hepatocyte growth factor (HGF) and Met/HGF receptor expression in
      ductal lesions of 46 human pancreata. Normal duct epithelium shows no significant
      immunoreactivity for either HGF or Met. Strong immunostaining for HGF was
      respectively demonstrated in hyperplastic and severely dysplastic epithelia in
      35.5 and 40% of cases with such duct lesions, whereas 37% of ductal
      adenocarcinoma showed diffuse HGF immunostaining. Positive Met immunostaining was
      demonstrated in 58, 80, and 78%, respectively, of specimens demonstrating the
      above duct lesions. Patients with resectable ductal adenocarcinoma demonstrating
      diffuse Met immunostaining have a significantly longer survival than those with
      tumors showing negative/focal staining (19.7 versus 8.1 months at P = 0.026). In
      contrast, HGF immunoreactivity did not significantly correlate with the survival
      of the patients. The results suggest that HGF and Met expression may play
      significant bifunctional roles during human pancreatic ductal carcinogenesis and
      progression. Whereas an upregulation of Met receptor expression and HGF-Met
      interaction may have an important pathogenetic role during the early stages of
      neoplastic promotion, a lack or subsequent loss of Met expression in invasive
      adenocarcinoma appears to result in a more aggressive clinical behavior.

PMID- 7573366
TI  - Genetic aberrations detected by comparative genomic hybridization predict outcome
      in node-negative breast cancer.
AB  - Breast cancer progression is determined by a complex pattern of multiple genetic
      aberrations the association of which with patient prognosis is unknown. In this
      study, we have undertaken a genome-wide screening to detect genetic changes
      associated with clinical outcome in node-negative breast cancer. Comparative
      genomic hybridization was used to screen for DNA sequence gains and losses across
      all human chromosomes in 23 tumors from node-negative breast cancer patients with
      no disease recurrence after at least 5 years of follow-up and in 25 node-negative
      patients with recurrence during the first 5 years of follow-up. The total number
      of genetic aberrations (copy number gains and losses) per tumor was significantly
      greater in the recurrence group (P = 0.019) and in the subgroup of these patients
      who died as a result of breast cancer (P = 0.0022). When copy number losses and
      gains were analyzed separately, only losses were significant (P = 0.013 for
      recurrence and P = 0.002 for overall survival). Of the individual loci involved,
      a high level gain of the long arm of chromosome 8 was significantly associated
      with recurrence (P = 0.01, Fisher's exact test). Furthermore, amplification of
      DNA sequences at chromosome 20q12-13 was found in 7 cases (15%), 6 of which had
      early recurrence within 32 months of diagnosis. This genome-wide overview by
      comparative genomic hybridization suggests that genetically advanced node
      negative breast cancers having a high overall number of genetic aberrations may
      have a poor prognosis and that increased copy number of two specific regions, 8q
      and 20q13, may confer a more aggressive phenotype. Results of this pilot study
      suggest that determination of the total number of DNA sequence copy number
      aberrations may help therapeutic decision making. Specific probes should be
      developed to test the prognostic value of 8q and 20q12-13 amplifications in large
      numbers of patients.

PMID- 7573367
TI  - CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on
      the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's
      disease.
AB  - Although CD40 has been extensively studied in B- and T-cell non-Hodgkin's
      lymphomas (NHLs)/leukemias, and more recently in Hodgkin's disease (HD), little
      is known about the expression of its ligand (CD40L) in lymphoproliferative
      disorders other than T-cell NHLs/leukemias. A series of 121 lymphoma/leukemia
      samples, including 35 cases of HD, 34 T-cell and 39 B-cells NHLs, 2 cases of
      adult T-cell leukemia/lymphoma, and 11 cases of T-cell acute lymphoblastic
      leukemia, were evaluated for CD40L expression by immunostaining of frozen tissue
      sections and flow cytometry with the anti-CD40L monoclonal antibody M90. CD40L
      was constitutively expressed by neoplastic cells in 15 of 36 (42%) T-cell
      NHLs/adult T-cell leukemia/lymphomas, almost invariably those displaying the
      CD4+/CD8- phenotype, whereas no CD40L-expressing tumor cells could be found in B
      cell NHL and HD. Among T-cell acute lymphoblastic leukemias, CD40L was detected
      only on 2 cases displaying a stem-cell-like phenotype. In follicular B-cell
      lymphomas a large number of CD40L-expressing CD3+/CD4+ T lymphocytes were found
      admixed with tumor cells within the neoplastic follicles and in their surrounding
      areas. In the nonfollicular B-cell lymphomas, CD40L-positive CD3+/CD4+ T
      lymphocytes were few or absent. In all HD subtypes other than the nodular
      lymphocytic predominance, CD40L-expressing CD3+/CD4+ T lymphocytes were numerous
      in the HD-involved areas and were mainly located in close proximity to the Reed
      Sternberg cells. Our data indicate that in human lymphomas CD40L is
      preferentially expressed by a restricted subset of T-cell lymphomas, mostly with
      CD4 immunophenotype. Finally, we have provided morphological evidence that CD40L
      may play an important role in the cell contact-dependent interaction of tumor B
      cells (CD40+) within the neoplastic follicles or Reed-Sternberg cells (CD40+) in
      HD-involved areas and the microenvironmental CD3+/CD4+/CD40L+ T lymphocytes.

PMID- 7573365
TI  - Novel fluorescence in situ hybridization approaches in solid tumors.
      Characterization of frozen specimens, touch preparations, and cytological
      preparations.
AB  - Fluorescence in situ hybridization has emerged as an extremely important tool for
      detection and characterization of nonrandom chromosome aberrations in cancer.
      Fluorescence in situ hybridization assays have been very reliable in cytogenetic
      tumor preparations, but have been more unpredictable in archival, paraffin
      embedded specimens. We describe novel approaches for detection of chromosome
      aberrations in frozen tumor specimens, touch preparations, and cytological
      preparations. These approaches are both simple and reproducible, with minimal
      case-to-case variation in hybridization efficiency or hybridization signal
      quality. We demonstrate potential applications of these novel approaches by
      evaluating: 1) significance of normal karyotypes in malignant peripheral nerve
      sheath tumors; 2) p15/p16 copy number in prostate cancer; and 3) clonal
      chromosome 3p deletion in cytological preparations of pleural fluid from patients
      with mesothelioma.

PMID- 7573368
TI  - Detection of heterogeneous Epstein-Barr virus gene expression patterns within
      individual post-transplantation lymphoproliferative disorders.
AB  - Using RT-PCR analysis of Epstein-Barr virus (EBV) latent gene transcription in
      EBV-harboring cell lines (JY and RAJI) and in post-transplantation
      lymphoproliferative disorders (PT-LPDs), we detected transcription of all tested
      latent genes (EBNA1, EBNA2, LMP1, LMP2A, and BARF0) in all cases, suggesting the
      presence of similar EBV expression patterns in both PT-LPDs and cell lines. In
      addition, the detection of immediate early (ZEBRA) and early gene (BHRF1)
      transcripts in cell lines and PT-LPDs indicates that activation of the virus
      lytic cycle occurs. To investigate EBV expression patterns at the single-cell
      level, a combination of immunohistochemistry and RNA in situ hybridization
      (including double-staining procedures) was used. In the JY and RAJI cell lines,
      the latency type 3 expression pattern was detected in 80 to 90% of the cells as
      shown by the co-expression of EBNA2 and LMP1. In contrast, in the three PT-LPDs
      that could be analyzed by double staining, cells expressing both EBNA2 and LMP1
      were rarely detected. A mixture of at least three different cell populations were
      identified: (1) cells exclusively expressing EBER1/2 and EBNA1 (latency type 1);
      (2) cells expressing EBER1/2, EBNA1, and LMP1 (latency type 2); and (3) cells
      expressing EBER1/2, EBNA1, and EBNA2 in the absence of LMP1. Activation of the
      lytic cycle was observed in a small minority of cells, as demonstrated by
      detection of ZEBRA and EA-D in all cases and GP350/220 in two cases. Thus, in
      contrast to EBV-transformed cell lines, the observed EBV gene expression pattern
      in PT-LPDs reflects a mixture of multiple EBV-harboring subpopulations expressing
      different subsets of EBV-encoded proteins. These data indicate that the
      operational definitions of EBV latencies in vitro cannot easily be applied to PT
      LPDs but that a continuum of different latency expression patterns can be
      detected at the single cell level in these lymphomas with, in a small minority of
      cells, progression to the virus lytic cycle.

PMID- 7573369
TI  - Aberrant GAP-43 gene expression in Alzheimer's disease.
AB  - GAP-43 is a growth-associated phosphoprotein expressed at high levels in neurons
      during development, axonal regeneration, and neuritic sprouting. GAP-43 gene
      expression in mature neurons is probably functionally important for the
      structural remodeling of synapses as required for learning and establishing new
      memory. The widespread aberrant neuritic growth accompanied by impaired synaptic
      plasticity in Alzheimer's disease (AD) suggests that abnormal GAP-43 gene
      expression may contribute to the cascade of neurodegeneration. In the present
      study, end-stage AD brains exhibited reduced neuronal expression but increased
      glial cell levels of GAP-43 mRNA and protein. Glial cell localization of GAP-43
      gene expression was confirmed by in situ hybridization of cerebral tissue,
      Northern blot analysis of microdissected cerebral white matter, and independent
      analysis of astrocytoma cell lines and primary malignant astrocytomas. In
      addition, in AD, GAP-43 immunoreactivity was translocated from the cytosol to
      membranes of swollen neuritic (dendritic) and glial cell processes throughout
      cerebral cortex and white matter. Downregulated and aberrant neuronal GAP-43 gene
      expression appears to reflect an important molecular lesion that precedes and
      progresses with the widespread synaptic disconnection and dementia in AD. At the
      same time, the presence of similar neuronal abnormalities in Pick's disease,
      diffuse Lewy body disease, Parkinson's disease, and Down syndrome suggests common
      mechanisms in the respective cascades of neurodegeneration. Finally, the finding
      of aberrantly increased glial cell GAP-43 gene expression in AD exposes a
      previously unrecognized neurodegenerative change that may account for the axonal
      loss and white matter atrophy detected early in the course of disease.

PMID- 7573371
TI  - Characterization of psoriasiform and alopecic skin lesions in HLA-B27 transgenic
      rats.
AB  - We have previously reported a multisystem inflammatory disease in transgenic rat
      lines with high expression of HLA-B*2705 and human beta 2 microglobulin. Skin
      disease in these rats includes two predominant lesions: 1) marked psoriasiform
      dermatitis of the tail and digits; and 2) progressive alopecia of face, neck,
      trunk, and extremities. Here we present the results of a systematic survey of
      these lesions. Tail and digit skin showed psoriasiform hyperplasia of the
      epidermis associated with parakeratosis, with marked dermal and epidermal
      inflammation. The alopecic skin showed perifollicular and follicular mononuclear
      infiltration and increased numbers of atrophic follicles. Immunohistochemical
      analysis revealed that B27 expression was prominent on keratinocytes in
      hyperplastic epidermis where lymphocytic infiltrates were prominent, but was
      absent in the absence of inflammation. In alopecic lesions, B27 was strongly
      expressed on follicular epithelium and dermal hair papillae associated with
      mononuclear infiltrates. T cells, both CD8 and CD4, were most prominent in
      inflammatory lesions and rat MHC-II expression on keratinocytes, and follicular
      epithelium was dramatically increased. This study suggests that T cell-mediated
      immune mechanisms participate in development of cutaneous lesions in HLA-B27
      transgenic rats.

PMID- 7573370
TI  - Transforming growth factor-beta in human cutaneous leishmaniasis.
AB  - Transforming growth factor (TGF)-beta has several downregulatory functions on the
      immune system: inhibition of interleukin-2 receptor induction, decrease of
      interferon-gamma-induced class II antigen expression, inhibition of macrophage
      activation, as well as cytotoxic and lymphokine-activated killer cell generation.
      TGF-beta has also been recognized as an important immunoregulator in murine
      leishmaniasis, for which it increases susceptibility to disease. In the present
      study we evaluate the involvement of TGF-beta in human leishmaniasis in vitro and
      in patients with cutaneous leishmaniasis. Human macrophages produce active TGF
      beta after infection by Leishmania amazonensis (480 +/- 44.7 pg/ml; mean +/-
      SEM), L. donovani chagasi (295 +/- 7.6 pg/ml), or L. braziliensis (196 +/- 15.7
      pg/ml). When TGF-beta was added to cultures of human macrophages infected with L.
      braziliensis it led to an increase of approximately 50% in parasite numbers as
      compared with untreated cultures. Exogenous TGF-beta added to macrophage cultures
      was able to reverse the effect of interferon-gamma in controlling Leishmania
      growth. Even at 100 IU/ml interferon-gamma the presence of TGF-beta increases the
      number of intracellular parasites. On the other hand, TNF-alpha at high
      concentration (100 IU/ml) totally blunts the suppressive effect of TGF-beta.
      Immunostaining for TGF-beta was observed in the dermis, produced by fibroblasts
      and occasionally by inflammatory cells in the biopsies from human leishmaniasis
      lesions, being present in most of the biopsies taken from patients with early
      cutaneous leishmaniasis (less than 2 months of ulcer development) and in cases of
      active mucosal leishmaniasis. Taken together these observations suggest an
      important role for TGF-beta in human leishmaniasis, with its production by
      infected macrophages being probably related to parasite establishment in the
      early stages of the disease.

PMID- 7573372
TI  - Embryonic fibronectin isoforms are synthesized in crescents in experimental
      autoimmune glomerulonephritis.
AB  - Crescents are a severe and stereotyped glomerular response to injury that occur
      in several forms of glomerulonephritis that progress to renal failure. The key
      pathogenetic step that leads to glomerular scarring in unknown, but fibronectin
      (FN), the clotting system, macrophages, and proliferating parietal epithelial
      cells are known to participate. This study was designed to determine whether FN
      is synthesized locally, and in what molecular isoform, and whether cytokines
      known to promote FN synthesis are present in the crescent. Rats immunized with
      bovine glomerular basement membrane develop cellular crescents by 14 days and
      fibrous crescents and glomerulosclerosis by 35 days. In situ hybridization was
      performed with oligonucleotides specific for sequences common to all FN isoforms
      (total FN) or sequences specific for the alternatively spliced segments (EIIIA,
      EIIIB, and V). Throughout the time period (14, 21, and 35 days) all crescents and
      glomerular tufts contained cells with strong ISH signals for total and V+ mRNA,
      with the strongest signals present in large cellular crescents at day 21. In
      contrast, EIIIA+ and EIIIB+ mRNAs showed maximal abundance within sclerosing
      crescents at 35 days. Protein deposition of EIIIA+, EIIIB+, and V+ FN isoforms
      was confirmed by immunofluorescence with segment-specific FN antibodies.
      Transforming growth factor-beta and interleukin-1 beta, both known to promote FN
      synthesis, were found in cellular crescents (days 14 and 21) and were still
      present, but greatly diminished, in the sclerotic phase (day 35). In summary,
      EIIIA-, EIIIB-, and V+ FN mRNA plasma isoforms predominate in cellular crescents,
      whereas in the fibrosing stage, mainly the oncofetal EIIIA+, EIIIB+, and V+
      isoforms are synthesized and accumulate.

PMID- 7573373
TI  - Nuclear localization of the antigen detected by ulcerative colitis-associated
      perinuclear antineutrophil cytoplasmic antibodies.
AB  - Antineutrophil cytoplasmic antibodies (ANCAs) identified in the serum of 50 to
      80% of ulcerative colitis (UC) patients yield a perinuclear staining pattern
      (pANCA) with alcohol-fixed neutrophils. The ANCAs of UC are distinguishable from
      those described for Wegener's granulomatosis and other vasculitidies. These
      various non-UC ANCAs recognize neutrophil granule constituents, but the antigenic
      moiety specific for the UC pANCA remains unknown. Although the perinuclear nature
      of some ANCA reactions is an artifact of the alcohol fixation of neutrophils,
      which causes cytoplasmic granules to redistribute around the nucleus, the UC
      pANCA reaction has been found not to be similarly affected. We postulated a
      nuclear localization for the UC-associated pANCA antigen and used both confocal
      laser microscopy and immunoelectron microscopy to examine the neutrophil reaction
      of UC-associated pANCA-containing sera. Confocal microscopy revealed a nuclear
      reaction for 88% (22/25) of the sera with 72% (18/25) showing the reaction
      localizing to the inner side of the nuclear (membrane) periphery. Immunoelectron
      microscopy showed that the UC-associated pANCA reaction localized primarily over
      chromatin concentrated toward the nuclear periphery, although the sera did not
      recognize double-stranded DNA. These results confirm the nuclear localization of
      the UC-associated pANCA antigen.

PMID- 7573376
TI  - Limb skeleton and locomotor adaptations of Apidium phiomense, an Oligocene
      anthropoid from Egypt.
AB  - Apidium phiomense is the most common primate from the early Oligocene deposits of
      Fayum, Egypt. It is known from hundreds of dental remains and dozens of skeletal
      remains, including numerous representatives of the long bones of the forelimb and
      hindlimb. Apidium phiomense was a small (1,600 g) arboreal quadruped. The
      forelimb bones of this species show features characteristic of arboreal
      quadrupeds and lack characteristic features found in the forelimb bones of
      vertial clingers, terrestrial quadrupeds, or suspensory species. The pelvis and
      hindlimb bones show numerous adaptations for leaping from a quadrupedal position.
      In general, Apidium lacks characteristic features of either cercopithecoid
      monkeys or hominoid apes. Overall, the skeleton shows greatest similarities to
      the same elements of small platyrrhines such as Saimiri and is also very similar
      to the hypothetical morphotype for ancestral platyrrhine. The skeleton of Apidium
      phiomense is the most primitive anthropoid postcranial skeleton known.

PMID- 7573375
TI  - Variation in pelvic size between males and females in nonhuman anthropoids.
AB  - Whether there is a sexual difference in phenotypic variance has been the subject
      of theoretical and empirical studies. The presence of such a difference is
      integral to some models on the evolution of sexual dimorphism. Several studies
      report that males are more variable than females for nonpelvic measures. This
      study tests for a sexual difference in variability of the pelvis. Phenotypic
      variance is a correlate of both the intensity and mode of selection. In both
      sexes, the pelvis is subject primarily to stabilizing selection. However,
      selection intensity is greater among females than among males because only among
      females does the pelvis function as a birth canal and, thereby, serve as a
      proximate cause of death. As selection intensity and phenotypic variability are
      inversely related under stabilizing selection, the implication is that females
      should be less variable than males in pelvic size and shape. However, the results
      of previous studies on this issue are equivocal or contradictory. This study
      compares the sexes for differences in pelvic variability by analyzing nine
      species (and ten samples) of nonhuman anthropoids. Data were collected on 16
      measures of the pelvis; only adults were used. Levene's univariate and
      multivariate tests for relative variation were used in the analysis. The results
      show that the sexes do not differ significantly in pelvic variability either
      within or among the nine samples of noncaptive anthropoids. Only in the one
      sample of captive specimens (Saimiri sciureus) do the sexes differ significantly
      in pelvic variability, with males being more variable than females. Two
      interpretations are derived from these results. First, the sexual difference in
      variability in captive Saimiri may be due either to a bias in the selection of
      Saimiri specimens by the captors/experimentors or to a sexual difference in
      growth associated with the stress of captivity. Second, the sexes do not differ
      in pelvic variability among noncaptive anthropoids because the anlage of the
      pelvis is bipotential in development. The intrinsic (i.e., agonadal) pattern of
      growth and development is that characteristic of a female. Testicular androgens
      are requisite to redirect the pattern of growth and development to that
      characteristic of a male. However, the redirected pattern of growth in males
      simply shifts en masse the intrinsic (i.e., female) distribution curve. The
      consequence among adults is sexual dimorphism in pelvic size, but sexual
      equivalency in relative pelvic variability.

PMID- 7573374
TI  - Increased elastin production in experimental granulomatous lung disease.
AB  - In the normal, healthy lung, elastin production is restricted to periods of
      development and growth. However, elastin expression in the adult lung has been
      observed in some forms of pulmonary injury, including pulmonary fibrosis. Here,
      we report that elastin production is significantly increased within precise
      interstitial compartments of the lung in an experimental model of granulomatous
      lung disease. An increase in the number and volume of elastic fibers within the
      alveolar walls was apparent on histological examination of Verhoeff-van Gieson
      stained sections of silicotic rat lungs. Quantitation of mature elastin cross
      links indicated that silicosis was accompanied by a 17-fold increase in lung
      elastin content when compared with values from saline-treated controls. In situ
      hybridization for tropoelastin mRNA revealed that elastin production was absent
      from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips,
      where a high density of elastic fibers is seen in the normal lung.
      Immunohistochemistry indicated tropoelastin was being expressed by alpha-smooth
      muscle actin-containing cells. Transforming growth factor-beta was
      immunolocalized to granulomatous regions of the silicotic lung but was absent
      from regions showing increased tropoelastin expression. These data indicate that
      the reinitiation of tropoelastin gene expression is associated with granulomatous
      lung disease, and this expression leads to the aberrant accumulation of mature
      elastin in the lung.

PMID- 7573377
TI  - Class I HLA antigens in two long-separated populations: Melanesians and South
      Amerinds.
AB  - Class I HLA antigens have been compared in 5,835 Melanesians of Papua New Guinea
      and 2,028 Amerindians of South America. The sample includes 50 PNGMel
      ethnolinguistic groups and 22 SAmInd groups. Both carry 15 serologically defined
      antigens and an undefined C allele. Except for A2 in Papua New Guinea and Cw1 in
      South America, these antigens are widely distributed in their respective
      populations. Nine (A2 and A24, B39, B60 and B62, and Cw1, Cw3, Cw4, and Cw7) are
      common to both. This commonality suggests that these two populations derive from
      an ancestral population with less polymorphism than modern East Asians. In both
      populations several theoretically possible haplotypes were absent, and other
      haplotypes were in positive disequilibrium in both. The parallels in
      disequilibria suggest that haplotypes are subject to selective forces acting on
      the level of allelic interaction. Based on three locus haplotype frequencies, the
      PNGMel groups form five clusters with internally typical linguistic and
      geographic characteristics and miscellaneous category, but SAmInd groups show no
      cluster.

PMID- 7573378
TI  - Socioeconomic change and patterns of growth in the Andes.
AB  - Changes in the pattern of growth over a 20-year period are described for a
      combined rural and semi-urban population in the District of Nunoa (Puno) in
      southern Peruvian Andes. Over the past two decades, Andean regions have
      experienced many socioeconomic changes, including the implementation of agrarian
      reform policies and increased integration into a market economy. Local changes in
      Nunoa have included improved transportation networks, new markets, an expanded
      public school system, and improved health care facilities. Secular trends in
      stature and weight have been found to be associated with social and economic
      development throughout the developing world, including Peru. The purpose of this
      paper is to present the findings from a re-study of growth in the Nunoan
      population, and to assess whether changing conditions in Nunoa have resulted in
      secular increases in growth. A cross-sectional sample of 1,466 children and
      adults and mixed-longitudinal sample of 404 children (age 3-22), measured between
      1983 and 1984, are compared to similar samples collected from the same location
      between 1964 and 1966. Adolescents are taller, heavier, and somewhat fatter in
      the present population, although these differences diminish or disappear in
      adulthood. Age of maturation, peak growth velocities, and cessation of growth may
      come 1 to 2 years earlier than in the 1960s. As was found in earlier studies,
      growth velocities are low, the adolescent growth spurt is small, and sexual
      dimorphism is delayed. No secular trends in adult stature were found. Thus, the
      effects of social and economic change on nutrition, health, and growth in the
      population are uneven and generally unclear. This points to inequalities in
      access to the benefits of change throughout the region.

PMID- 7573379
TI  - Brief communication: non-circular geometry and radiogrammetry of the second
      metacarpal.
AB  - Traditional radiogrammetry of the second metacarpal midshaft reconstructs
      cortical cross-sectional geometry from mediolateral (ML) linear dimensions based
      on circular model. However, comparison of anteroposterior (AP) versus
      mediolateral radiographic dimensions in a sample of paired metacarpals shows that
      AP total and medullary widths typically exceed ML widths by 5% to 10%. As well,
      in 13% of males and 25% of females, the two metacarpals are dissimilarly shaped,
      i.e., the AP/ML ratio is > 1.0 for one side and < 1.0 for the other. This
      situation exaggerates the differences in geometric properties between sides and
      constitutes a potentially significant source of bias for analyses of bilateral
      asymmetry. These results suggest that the circular model is inappropriate for
      estimation of cross-sectional geometry at this anatomical location.

PMID- 7573380
TI  - Stereolithography: potential applications in anthropological studies.

PMID- 7573381
TI  - Energetic efficiency of human bipedality.

PMID- 7573382
TI  - Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and K+
      channel-opening drugs.
AB  - ATP-sensitive K+ (KATP) channels are present at high density in membranes of
      cardiac cells where they regulate cardiac function during cellular metabolic
      impairment. KATP channels have been implicated in the shortening of the action
      potential duration and the cellular loss of K+ that occurs during metabolic
      inhibition. KATP channels have been associated with the cardioprotective
      mechanism of ischemia-related preconditioning. Intracellular ATP (ATPi) is the
      main regulator of KATP channels. ATPi has two functions: 1) to close the channel
      (ligand function) and 2) in the presence of Mg2+, to maintain the activity of
      KATP channels (presumably through an enzymatic reaction). KATP channel activity
      is modulated by intracellular nucleoside diphosphates that antagonize the ATPi
      induced inhibition of channel opening or induce KATP channels to open. How
      nucleotides will affect KATP channels depends on the state of the channel. K+
      channel-opening drugs are pharmacological agents that enhance KATP channel
      activity through different mechanisms and have great potential in the management
      of cardiovascular conditions. KATP channel activity is also modulated by
      neurohormones. Adenosine, through the activation of a GTP-binding protein,
      antagonizes the ATPi-induced channel closure. Understanding the molecular
      mechanisms that underlie KATP channel regulation should prove essential to
      further define the function of KATP channels and to elucidate the pharmacological
      regulation of this channel protein. Since the molecular structure of the KATP
      channel has now become available, it is anticipated that major progress in the
      KATP channel field will be achieved.

PMID- 7573384
TI  - Relationships between mesangial cell proliferation and types I and IV collagen
      mRNA levels in vitro.
AB  - Changes in the composition of the mesangial extracellular matrix (ECM) and cell
      turnover are present in glomerular disease. To determine if ECM changes play a
      role in perpetuating mesangial cell dysfunction, we examined a line of mouse
      mesangial cells cultured on films or gels of several ECM components and also on
      methyl cellulose, an inert substrate that prevents attachment. Cells on films of
      fibronectin or type IV or I collagen had persistently high growth rates and high
      levels of alpha 1-I and alpha 1-IV collagen mRNAs. In contrast, on gels of type
      IV or I collagen or matrigel, the growth rate was low. The alpha 1-IV collagen
      mRNA levels were low on type IV collagen gel or matrigel, whereas the alpha 1-I
      collagen mRNA levels remained high. In contrast, the alpha 1-I collagen mRNA
      levels were low on type I collagen gel, and the alpha 1-IV collagen mRNA levels
      were high. Cells on methyl cellulose formed floating aggregates, did not
      proliferate, and had a 5- to 10-fold decrease in both alpha 1-I and alpha 1-IV
      collagen mRNA levels. These phenotypic changes were largely reversible. Finally,
      when matrigel was layered over cells on fibronectin films, alpha 1-IV collagen
      mRNA levels decreased, but alpha 1-I collagen mRNA levels and proliferation
      remained high. Thus proliferation and alpha 1-I and alpha 1-IV collagen mRNA
      levels in mesangial cells were independently regulated and depended on attachment
      and the nature of the adjacent matrix.

PMID- 7573383
TI  - Effects of peroxide and superoxide on coronary artery: ANG II response and
      sarcoplasmic reticulum Ca2+ pump.
AB  - The sarcoplasmic reticulum (SR) Ca2+ pump in membranes isolated from arterial
      smooth muscle is damaged by reactive oxygen species (ROS). Because angiotensin II
      (ANG II) contracts arterial smooth muscle by mobilizing intracellular Ca2+
      concentrations ([Ca2+])i, we determined the effects of ROS pretreatment on ANG II
      induced contractions in coronary artery rings and [Ca2+]i transients in smooth
      muscle cells (SMC) cultured from them. This experimental design eliminates direct
      ROS interference in assay solutions, thus monitoring only the tissue damage.
      Pretreating the arteries with peroxide inhibited the ANG II contractions with the
      concentration for half-maximal activation (K0.5) = 74 +/- 5 microM. Peroxide (250
      microM) inhibited the contractions to ANG II and cyclopiazonic acid (CPA, SR
      Ca(2+)-pump inhibitor) by 78.3 +/- 5.1 and 67.4 +/- 6.3%, respectively, but did
      not significantly affect the contractions by 60 mM KCl. Pretreating SMC with
      peroxide inhibited the ANG II-induced increase in [Ca2+]i with K0.5 = 24 +/- 3
      microM for peroxide. Peroxide (100 microM) inhibited the increase in [Ca2+]i in
      response to ANG II and CPA by 78.9 +/- 5.1 and 38.3 +/- 4.9%, respectively. The
      SR Ca(2+)-pump activity was also measured as the Ca(2+)-dependent formation of
      115-kDa acylphosphate. Pretreating SMC with 100 microM peroxide inhibited the
      acylphosphate levels by 36.3 +/- 3.2%. Peroxide (100 microM) pretreatment of SMC
      did not significantly affect their ANG II binding.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7573386
TI  - Role of [Na+]i and [Ca2+]i in nicotine-induced norepinephrine release from bovine
      adrenal chromaffin cells.
AB  - Intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) concentrations were
      determined by sodium-binding benzofuran isophthalate (SBFI) and fura 2
      microfluorimetry, respectively, in bovine adrenal chromaffin cells (BCC).
      Validation of SBFI microfluorimetry by in vitro and in vivo calibration revealed
      a reliable assessment of [Na+]i within a range of 1-30 mM in single BCC. Nicotine
      (0.1-10 microM) induced concentration-dependent increases of both [Na+]i (from
      3.3 +/- 0.1 to 25.6 +/- 0.4 mM, n = 76, P < 0.001) and [Ca2+]i (from 64 +/- 1 to
      467 +/- 16 nM, n = 87, P < 0.001), which were accompanied by an increase in
      [3H]norepinephrine (NE) release. Consistent with an exocytotic release mechanism,
      nicotine-induced increments of [Ca2+]i and [3H]NE release were reduced under
      calcium-free conditions and by gadolinium chloride (40 microM), whereas [Na+]i
      was not affected. In contrast, a parallel attenuation of nicotine-evoked changes
      in [Na+]i, [Ca2+]i, and [3H]NE release was observed during reduction of the
      extracellular sodium concentration. The nicotine-evoked responses were
      neutralized by the nicotinic receptor antagonist hexamethonium (100 microM) but
      not by blockade of voltage-dependent sodium channels (1 microM tetrodotoxin). In
      conclusion, the nicotine-induced exocytotic release of [3H]NE is triggered by an
      increase in [Ca2+]i, which is facilitated by sodium influx through the nicotinic
      receptor ionophore.

PMID- 7573387
TI  - Actions of palytoxin on Na+ and Ca2+ homeostasis in human osteoblast-like Saos-2
      cells.
AB  - Palytoxin (PTx) is a potent membrane-active agent produced by marine
      coelenterates that acts to stimulate bone resorption in organ culture at
      nanomolar concentrations. We report here the actions of PTx on Na+ and Ca2+
      homeostasis in human osteoblast-like Saos-2 cells. PTx induced a rise in the
      cytosolic free Na+ concentration ([Na]i) by causing entry of extracellular Na+
      (Na(e)+). PTx also caused a concentration-dependent biphasic rise in the
      cytosolic free Ca2+ concentration ([Ca2+]i) by enhancing entry of extracellular
      Ca2+ (Ca(e)2+). Entry of Na+ was dependent on the presence of Ca(e)2+ and was
      prevented by the Na+/Ca2+ exchange antagonist 3,4-dichlorobenzamil (DCB). Entry
      of Ca2+ was dependent on the presence of Na(e)+ but was not prevented by DCB. The
      actions of PTx on [Na+]i and [Ca2+]i were completely inhibited by pretreatment of
      the cells with ouabain. Ouabain alone had no acute effect on [Na+]i or [Ca2+]i in
      Saos-2 cells. We propose that interaction of PTx with the Na+ pump created a
      channel that allowed influx of Na(e)+ and Ca(e)2+. The rise in [Ca2+]i then
      stimulated the activity of the plasma membrane Na+/Ca2+ exchanger, which further
      enhanced Na(e)+ entry.

PMID- 7573385
TI  - Polyamines inhibit myosin phosphatase and increase LC20 phosphorylation and force
      in smooth muscle.
AB  - The increase in Ca(2+)-activated force caused by polyamines in beta-escin
      permeabilized guinda pig ileum is shown to be associated with increased myosin 20
      kDa light chain (LC20) phosphorylation and shortening velocity. Myosin LC20
      dephosphorylation with arrested kinase activity was slower in the presence of 1
      mM spermine. Smooth muscle phosphatases (SMP-I, -II, -III, and -IV) isolated from
      turkey gizzard are all active against phosphorylated LC20, but only SMP-III and 
      IV dephosphorylate heavy meromyosin (HMM). Spermine inhibited SMP-III activity
      toward LC20 but stimulated HMM dephosphorylation, whereas SMP-IV was inhibited
      with both substrates. In contrast, SMP-I and -II were stimulated by spermine. The
      relative effects of different polyamines correlated with an increasing number of
      positive charges. Spermine did not affect binding of SMP-IV to myosin and did not
      dissociate any of the subunits of the enzyme. Incubation of permeabilized strips
      with SMP-IV resulted in attenuated responses to Ca2+, an effect that was opposed
      by spermine and abolished by microcystin-LR. We conclude that spermine
      selectively inhibits myosin phosphatase activity and suggest that polyamines
      function as endogenous myosin phosphatase inhibitors.

PMID- 7573388
TI  - Changes in lens connexin expression lead to increased gap junctional voltage
      dependence and conductance.
AB  - The differentiation of mouse lens epithelial cells into fiber cells is a useful
      model for studying the changes of the electrical properties of gap junction (cell
      to-cell) channels that are induced by an alteration in connexin expression
      patterns. In this model, cuboidal lens epithelial cells differentiate into
      elongated fiber cells, and the expression of connexin43 (Cx43) in the epithelial
      cells is replaced with the production of high levels of Cx50 and Cx46 in the
      fiber cells. We now report a new procedure to isolate mouse lens fiber cell pairs
      suitable for double whole cell patch-clamp analysis. Analysis was also performed
      for fiberlike cell pairs differentiated from epithelial cells in culture. Voltage
      dependence and unitary conductance of fiber cell gap junction channels were
      determined and compared with the corresponding values previously measured for the
      channels joining lens epithelial cells and for lens connexin channels formed in
      Xenopus oocyte pairs. Our results support a differentiation-induced shift toward
      stronger gap junctional voltage dependence and larger unitary conductances in the
      fiber cells. Our data further reflect a balanced functional contribution of Cx50
      and Cx46 in the fiber cell-to-cell channels rather than a predominance of a
      single connexin.

PMID- 7573389
TI  - Immunopurification and functional reconstitution of a Na+ channel complex from
      rat lymphocytes.
AB  - Patch-clamp experiments have demonstrated an amiloride-sensitive Na+ conductance
      in human B lymphoid cells. We measured whole cell currents in rat lymphocytes and
      observed a similar Na(+)-specific inward conductance. The presence of 400 microM
      8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate in the bath
      significantly increased the inward current, and this adenosine 3',5'-cyclic
      monophosphate activation was abolished by 2 microM amiloride. We immunopurified a
      protein complex from rat lymphocyte membranes using an anti-bovine kidney Na+
      channel antibody. The complex consisted of five distinct polypeptides with
      apparent M(r) values of 110,000, 92,000, 59,000, 48,000, and 42,000. This
      putative channel complex was incorporated into planar lipid bilayers, where we
      observed single Na+ channel activity that was blocked by amiloride in a
      concentration-dependent manner. The addition of protein kinase A and ATP to the
      "intracellular" solution elicited a twofold increase in channel activity. Reverse
      transcription-polymerase chain reaction analysis was used to determine if the rat
      lymphocytes express the message for the recently cloned Na+ channel of the rat
      colon (rENaC). Primers for the alpha-subunit of rENaC identified no message in
      the lymphocyte RNA, while primers for the beta-subunit of the clone produced low
      levels of the expected product. Thus it appears that a rENaC-like beta-subunit
      may be an essential component of the lymphocyte Na+ channel that was isolated. At
      the same time, this channel is different from those recently cloned in that it
      does not include an alpha-subunit homologous to that of rENaC.

PMID- 7573390
TI  - Effects of magnesium on nitric oxide synthase activity in endothelial cells.
AB  - Magnesium modulates endothelium-dependent vasodilation in intact blood vessels.
      Therefore, the effects of magnesium on nitric oxide (NO) release by isolated
      endothelial cells and nitric oxide synthase (NOS) activity in endothelial cell
      homogenates were studied. Unstimulated and bradykinin-stimulated NO release by
      porcine aortic endothelial cell (PAEC) monolayers were unaffected by 30 min of
      exposure to magnesium concentrations varying from 0.010 to 10.0 mM. In contrast,
      when A-23187-stimulated cells were exposed to 0.01, 3.16, and 10.0 mM MgCl2, NO
      release was decreased by 11.3 +/- 1.8, 11.7 +/- 3.0, and 20.3 +/- 7.2%,
      respectively, compared with cells exposed to 1.0 mM MgCl2 (P < 0.01). These data
      suggested that a change in the intracellular magnesium concentration had an
      effect on NO release, in contrast to a change in the extracellular concentration,
      which did not have an effect. To further assess this possibility, crude NOS
      extracts were prepared from PAEC and exposed to MgCl2. NOS activity was measured
      via the conversion of L-[3H]arginine to L-[3H]citrulline. Increasing the
      concentration of MgCl2 by 1.0, 3.16, and 10.0 mM caused a 16.0 +/- 6.8, 17.1 +/-
      1.7, and 38.6 +/- 5.3% decrease in citrulline formation, respectively (P < 0.05),
      suggesting a direct inhibition of NOS by MgCl2. No significant difference in the
      degree of inhibition of NOS activity was found between MgSO4 and MgCl2, thus
      ruling out a nonspecific chloride effect. In addition, increasing the
      concentration of NaCl to 15 mM had no effect on NOS activity, ruling out a
      nonspecific osmotic effect [101.6 +/- 10.5% of control activity, P = not
      significant (NS)].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573391
TI  - mRNAs of enzymes involved in energy metabolism and mtDNA are increased in
      endurance-trained athletes.
AB  - Improvements in endurance capacity by training are associated with structural and
      biochemical adaptations of working muscles that affect the mitochondrial
      compartment. We investigated whether the 1.8-fold higher mitochondrial volume
      density in a group of endurance-trained athletes compared with untrained subjects
      was reflected by higher steady-state levels of mRNAs coding for components of the
      oxidative phosphorylation pathway using a quantitative polymerase chain reaction
      approach. We found that mitochondrially encoded RNAs (cytochrome-c oxidase
      subunit I, NADH reductase subunit 6, 16S rRNA), as well as nuclear-encoded RNAs
      (cytochrome-c oxidase subunit IV, succinate dehydrogenase, fumarase) are all
      increased coordinately in the athletes (1.54- to 1.94-fold). In addition,
      mitochondrial (mt) DNA concentration was also 1.55-fold higher in the trained
      athletes, whereas genomic DNA was not changed. Our findings thus show similar RNA
      expression of mitochondrially encoded genes in sedentary and endurance-trained
      subjects, whereas pretranslational control mechanisms account for higher levels
      of nuclear-encoded RNAs in the athletes.

PMID- 7573392
TI  - Rabbit pancreatic acini express CFTR as a cAMP-activated chloride efflux pathway.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for
      adenosine 3',5'-cyclic monophosphate (cAMP)-activated chloride transport in
      epithelial cells. Isolated rabbit pancreatic acini possess a cAMP-activated
      chloride efflux mechanism distinct from zymogen granule secretion. To determine
      whether CFTR is expressed in acini, we used polymerase chain reaction (PCR) to
      amplify a 480-base pair (bp) sequence from reverse-transcribed rabbit acinar RNA.
      The PCR product was consistent with a 480-bp band amplified in T84 cells, and its
      sequence was > 90% homologous to human CFTR. CFTR antibody M3A7 recognized a 180-
      and a 160-kDa protein from acinar membranes consistent with bands seen in Chinese
      hamster ovary (CHO) cells transfected with CFTR. To determine if CFTR was
      responsible for the cAMP-activated chloride efflux previously demonstrated in
      pancreatic acini, we incubated acinar cells for 20 h with 1.75 microM CFTR
      antisense or sense oligodeoxynucleotide. Chloride efflux, in response to 8
      bromoadenosine 3',5'-cyclic monophosphate and phorbol ester but not to calcium
      ionophore, was selectively inhibited by CFTR antisense oligodeoxynucleotide.
      Antisense oligodeoxynucleotide did not inhibit acinar amylase secretion. These
      findings indicate that isolated pancreatic acini can be used for future studies
      of CFTR expression and function.

PMID- 7573393
TI  - [Ca2+]i transients in hypertensive and postinfarction myocytes.
AB  - Changes in intracellular calcium concentration ([Ca2+]i) in paced fura 2-loaded
      myocytes isolated from Sham, renovascular hypertensive (Hyp), and myocardial
      infarcted (MI) rats were examined. Compared with controls, Hyp myocytes paced at
      physiological rates had similar systolic but elevated diastolic [Ca2+]i. By
      contrast, systolic [Ca2+]i was significantly lower and diastolic [Ca2+]i higher
      in MI myocytes. The different patterns of alterations in [Ca2+]i dynamics in Hyp
      and MI myocytes may partly explain predominantly diastolic dysfunction in
      hypertensive hearts and systolic dysfunction in hearts surviving MI. In the
      presence of 1 microM isoproterenol, both Hyp and MI myocytes had much lower
      systolic [Ca2+]i when compared with their respective controls. Isoproterenol
      restored the elevated diastolic [Ca2+]i in Hyp myocytes toward normal but had no
      effect on the intrinsic differences in diastolic [Ca2+]i between Sham and MI
      myocytes. The observation that isoproterenol lowers diastolic [Ca2+]i in Hyp
      myocytes toward normal may provide a cellular mechanism for the lack of efficacy
      of beta-adrenergic blockers to improve diastolic compliance in patients with
      hypertensive hypertrophic cardiomyopathy.

PMID- 7573395
TI  - Redistribution of aquaporin-2 water channels induced by vasopressin in rat kidney
      inner medullary collecting duct.
AB  - Aquaporin-2 (AQP2) is the predominant vasopressin-regulated water channel of the
      renal collecting duct. We tested whether vasopressin induces translocation of
      AQP2 from intracellular vesicles into the apical plasma membrane. AQP2 was
      quantitated in plasma membrane and intracellular vesicle fractions prepared from
      the inner medulla of one kidney from each rat before or 20 min after intravenous
      1-desamino-8-D-arginine vasopressin (DDAVP) treatment, using immunoblotting and
      densitometry. Contralateral kidneys were prepared for immunofluorescence and
      immunoelectron microscopy. Immunoblotting revealed that, compared with untreated
      controls, DDAVP treatment significantly increased the fraction of AQP2 protein
      associated with the plasma membrane fraction relative to intracellular vesicles.
      This increase averaged 2.0-fold in untreated rats and 2.9-fold in rats water
      loaded for 12 h. Water loading, presumably by suppressing circulating vasopressin
      levels, decreased the fraction of AQP2 associated with the plasma membrane by
      55%, suggesting retrieval of AQP2 from the plasma membrane. In rats sequentially
      thirsted for 48 h to increase expression and then water loaded for 72 h to
      minimize plasma membrane labeling, DDAVP caused a 12-fold increase in the plasma
      membrane to intracellular vesicle labeling ratio. The accentuation of the DDAVP
      response seen after water loading is consistent with the observed increase in the
      fraction of AQP2 in the intracellular pool available for insertion.
      Immunofluorescence confirmed a marked DDAVP-induced redistribution of AQP2 from
      intracellular to plasma membrane domains. Furthermore, quantitative
      immunoelectron microscopy demonstrated a 3.4-fold increase in apical plasma
      membrane to intracellular vesicle labeling ratio. These results provide a direct
      in vivo demonstration of vasopressin-induced translocation of AQP2 into the
      apical plasma membrane.

PMID- 7573394
TI  - Cloning of a bovine renal epithelial Na+ channel subunit.
AB  - A bovine homologue of the rat and human epithelial Na+ channel subunits, alpha
      rENaC and alpha-hENaC, was cloned. The cDNA clone, termed alpha-bENaC, was
      isolated from a bovine renal papillary collecting duct cDNA expression library.
      The bovine cDNA is 3,584 base pairs (bp) long, has an open reading frame of 2,094
      bp encoding a 697-amino acid protein, and is 75-85% homologous to its rat and
      human counterparts. In vitro translation of the transcribed cRNA yields an 80-kDa
      polypeptide and one at 92 kDa in the presence of pancreatic microsomes. The clone
      exhibits consensus sequences for N-linked glycosylation and for phosphorylation
      by protein kinase C, but not for protein kinase A. After expression in Xenopus
      laevis oocytes, a small amiloride-sensitive Na+ conductance that exhibited inward
      rectification and a reversal potential greater than +30 mV, consistent with the
      predicted equilibrium potential for Na+, was identified. The expressed alpha
      bENaC-associated Na+ current was not responsive to elevations in adenosine 3',5'
      cyclic monophosphate but could be stimulated by phorbol 12-myristate 13-acetate,
      an activator of protein kinase C. alpha-bENaC also formed amiloride-sensitive
      chimeric channels when coexpressed with the rat beta- and gamma-ENaC subunits in
      Xenopus oocytes. alpha-bENaC therefore represents a novel isoform of a growing
      family of epithelial Na+ channels.

PMID- 7573396
TI  - M-creatine kinase gene expression in mechanically overloaded skeletal muscle of
      transgenic mice.
AB  - The molecular pathways and regulatory molecules that underlie changes in gene
      transcription during mechanical overload of skeletal muscle remain obscure. To
      better understand this process, we have examined mouse muscle creatine kinase
      (MCK) gene expression in mechanically overloaded plantaris (OP) muscle of
      transgenic and nontransgenic mice. Northern blot analysis revealed that
      endogenous MCK-specific mRNA transcripts were decreased 150% in the OP muscles
      after 6 wk. To identify the MCK gene regions involved in the response to
      mechanical overload, three different mouse MCKCAT transgenes were studied by
      measuring chloramphenicol acetyltransferase (CAT assays) activity in OP and sham
      operated (control plantaris) muscles. Mouse lines carrying (+enh206)117MCKCAT and
      -1256MCKCAT transgenes exhibited 30 and 40% lower CAT levels, whereas two mouse
      lines carrying -3300MCKCAT transgenes exhibited average decreases of 430%. Nearly
      identical results, including measurements of exogenous CAT mRNA, were obtained 2
      days postoverload. Six weeks or 2 days of mechanical overload led to an average
      decrease in MM-CK isoprotein of 140%. These data provide evidence that mechanical
      overload induces changes in MCK gene expression that appear to be regulated by at
      least two portions of the MCK gene: the 206 base pair 5' enhancer and the -3,300
      to -1,257 region.

PMID- 7573397
TI  - Reciprocal regulation of cardiac Na-K-ATPase and Na/Ca exchanger: hypertension,
      thyroid hormone, development.
AB  - Inhibiting cardiac Na pump activity decreases the driving force for the Na/Ca
      exchanger transport that increases cellular Ca stores and contractility.
      Decreased abundance of Na pumps would be expected to have the same effect as
      decreased activity unless there was reciprocal regulation of Na/Ca exchanger
      expression to oppose the effects of depressed Na pump activity on intracellular
      Ca stores. The aim of this study was to test the hypothesis that cardiac Na/Ca
      exchanger abundance is regulated in a reciprocal fashion to Na-K-ATPase abundance
      in a number of models known to have altered Na-K-ATPase abundance. In
      renovascular hypertension, cardiac ventricular Na-K-ATPase alpha 1-levels are
      unaltered, alpha 2-isoform subunit mRNA and protein levels decrease to 0.76 +/-
      0.06 and 0.56 +/- 0.07 of control, respectively, and the Na/Ca exchanger protein
      (not mRNA) increased 1.35 +/- 0.11-fold. In the transition from hypothyroid to
      hyperthyroid cardiac alpha 1 doubles, alpha 2-protein increases 8.83 +/- 1.06
      fold, and the Na/Ca exchanger protein decreases to 0.64 +/- 0.11. A similar
      pattern was seen during cardiac development in the preweaning rat heart.
      Treatment with the antiarrhythymic amiodarone has no effect on alpha 1, decreases
      alpha 2-protein expression to 0.51 +/- 0.08 of control, and increases exchanger
      expression 1.42 +/- 0.16-fold. In conclusion, the reciprocal regulation of the
      Na/Ca exchanger and of Na-K-ATPase alpha 2-expression provides evidence for a
      homeostatic mechanism that would oppose the changes in cellular Ca stores driven
      by the changes in Na-K-ATPase activity.

PMID- 7573398
TI  - CFTR mediates electrogenic chloride secretion in mouse inner medullary collecting
      duct (mIMCD-K2) cells.
AB  - Previously we demonstrated that the inner medullary collecting duct cell line
      mIMCD-K2 secretes Cl- by an electrogenic mechanism [N. L. Kizer, B. Lewis, and B.
      A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355,
      1995; N. L. Kizer, D. Vandorpe, B. Lewis, B. Bunting, J. Russell, and B. A.
      Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861,
      1995]. The goal of the present study was to characterize the Cl- channel
      responsible for adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated Cl-
      secretion. To this end, using the patch-clamp technique, we measured Cl-
      currents. In whole cell patch-clamp experiments, 8-(4-chlorophenylthio)adenosine
      3',5'-cyclic monophosphate (CPT-cAMP) activated Cl- currents that were time and
      voltage independent, inhibited by diphenylamine 2-carboxylate (DPC), and had a
      linear current-voltage (I-V) relation. In cell-attached patches of the apical
      membrane, we identified 7-pS Cl- channels that were stimulated by CPT-cAMP. In
      inside-out patches with Cl- in the pipette and bath solutions, Cl- currents had a
      linear I-V relation. The halide permeability sequence was PCl = PBr > PI. The Cl-
      channel inhibitors DPC, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, and
      glibenclamide blocked the 7-pS Cl- channel, whereas 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid was ineffective. By reverse transcriptase polymerase chain
      reaction, we isolated a partial cDNA clone encoding the cystic fibrosis
      transmembrane conductance regulator in mIMCD-K2 cells. We conclude that cAMP
      stimulates electrogenic Cl- secretion in inner medullary collecting duct cells by
      activating cystic fibrosis transmembrane conductance regulator Cl- channels.

PMID- 7573399
TI  - Effect of stretch on contraction and the Ca2+ transient in ferret ventricular
      muscles during hypoxia and acidosis.
AB  - The effect of stretch on cardiac muscle contraction and the Ca2+ transient was
      studied during hypoxia and acidosis in isolated ferret ventricular muscles. In
      control conditions, a maintained stretch produced an immediate increase in
      tension followed by a slow increase in tension and the Ca2+ transient. A stretch
      between contractions (diastolic stretch) caused only a slow increase in tension
      and the Ca2+ transient, whereas a stretch during the period of contraction
      (systolic stretch) produced an immediate increase in tension followed by a small
      slow increase in tension and the Ca2+ transient. In hypoxia, the immediate
      percent increase in tension was the same as in control. However, the slow
      increase was smaller during all three types of stretch. In acidosis, the
      immediate percent increase in tension was larger than in control. The slow change
      was the same during maintained stretch. However, the slow increase in tension was
      smaller during diastolic stretch and larger during systolic stretch. Thus the
      stretch-dependent increase in contraction is inhibited during hypoxia and
      modulated by acidosis.

PMID- 7573401
TI  - Experimental acidemia and muscle cell pH in chronic acidosis and renal failure.
AB  - To test whether muscle intracellular pH (pHi) decreases when extracellular pH
      falls, 31P-nuclear magnetic resonance was utilized in rats made acidotic by
      infusion of HCl, gavage-feeding NH4Cl, or induction of chronic renal failure
      (CRF). A 2- or 4-h HCl infusion did not lower muscle pHi, even though serum
      bicarbonate fell to 5 mM. With chronic acidemia, blood pH was 7.15 +/- 0.01 vs.
      7.38 +/- 0.02 in pair-fed controls, and muscle pHi was 7.09 +/- 0.01 and 7.14 +/-
      0.02, respectively (P < 0.01). pHi in muscle of CRF rats (7.16 +/- 0.01) did not
      differ from sham-operated, pair-fed controls (7.19 +/- 0.01) despite a blood pH
      of 7.23 +/- 0.05 in CRF vs. 7.39 +/- 0.01 in controls. Because ion transport is
      abnormal in CRF, we examined whether recovery of pHi is impaired when muscles of
      six CRF and control rats were exercised to tetany by stimulation of the sciatic
      nerve. Neither pHi nor the recovery of pHi differed between CRF and control rats.
      We conclude that pHi is maintained in muscle in uremia and that signals other
      than changing pHi must be necessary to disrupt metabolism.

PMID- 7573400
TI  - Measurement of SR free Ca2+ and Mg2+ in permeabilized smooth muscle cells with
      use of furaptra.
AB  - The concentrations of intrasarcoplasmic reticulum (SR) free Ca2+ ([Ca2+]SR) and
      Mg2+ ([Mg2+]SR) were measured in furaptra-loaded saponin-permeabilized cultured
      aortic smooth muscle (A7r5) cells. Ca(2+)-independent fluorescence emitted by
      furaptra trapped within organelles, excited at 346 nm (isosbestic point),
      decreased with a half time of 30 min. All Ca2+ measurements appeared to be from
      SR, because the apparent Ca2+ distribution within permeabilized cells was uniform
      and therefore inconsistent with furaptra loading into mitochondria. Moreover,
      thapsigargin-induced SR Ca(2+)-adenosinetriphosphatase inhibition caused near
      total depletion of Ca2+, and the metabolic poisons oligomycin and rotenone had no
      effect. Calibration curves relating 370 nm-to-346 nm ratios to [Ca2+] and to
      [Mg2+] were calculated in situ; dissociation constants for Ca2+ and Mg2+ binding
      were 49 microM and 6.8 mM, respectively. Resting [Ca2+]SR was 75-130 microM, with
      a mean of 97.2 +/- 2.2 microM (n = 376), whereas [Mg2+]SR, estimated in the
      absence of Ca2+, was 1.0 mM. Stimulation with inositol 1,4,5-trisphosphate
      resulted in time-dependent declines in [Ca2+]SR, and pretreatment with guanosine
      5'-triphosphate caused a large increase in the rate of inositol 1,4,5
      trisphosphate-evoked SR Ca2+ release, although guanosine 5'-triphosphate had no
      effect by itself. These observations indicate that furaptra will be a valuable
      tool with which to directly study [Ca2+]SR and SR function.

PMID- 7573402
TI  - Myosin phosphorylation augments force-displacement and force-velocity
      relationships of mouse fast muscle.
AB  - Two studies were conducted to examine the effect of myosin regulatory light chain
      (R-LC) phosphorylation on the rate and extent of shortening in submaximally
      activated mouse extensor digitorum longus muscles in vitro at 25 degrees C. For
      each study, R-LC phosphate content was increased fivefold by application of a 5
      Hz, 20-s conditioning stimulus (CS) to 0.65-0.68 mol phosphate/mol R-LC; this
      level was sustained between 10 and 40 s after the CS. Maximum isometric twitch
      force and the maximum rate of force development (+dF/dtmax) were potentiated in
      the range 13-17% and 9-17% (P < 0.05), respectively, after the CS. In study 1,
      the maximal rate and extent of shortening were significantly enhanced by 10 and
      21% (P < 0.001), respectively, when measured using a twitch zero-load clamp
      technique. In study 2, the force-velocity and force-displacement relationships
      were both augmented when determined with the twitch afterload technique.
      Displacement was enhanced between 20 and 82% for loads that ranged from 3 to 75%
      of active peak twitch force, whereas velocity was increased 6-8% over the same
      range (P < 0.05), including the predicted maximum velocity (Vmax; 5.08 vs. 4.69
      muscle length/s). In both studies the increase in velocity likely represents a
      shift along the force-velocity relationship toward true Vmax that reflects a
      decrease in relative load due to force potentiation. Furthermore, with the
      decrease in relative load, displacement at a given load was also increased.
      Potentiated displacement and extent of R-LC phosphorylation also decreased in
      parallel when studied for 5 min after the CS. The increase in muscle shortening
      is a novel finding and suggests a function for R-LC phosphorylation with respect
      to movement because both peak work and power were also enhanced by up to 22%.
      These effects are consistent with an R-LC phosphorylation-induced increase in
      fapp, the apparent rate constant that describes the cross-bridge transition from
      the non-force-generating to the force-generating state.

PMID- 7573403
TI  - Voltage-dependent potentiation of neuronal L-type calcium channels due to state
      dependent phosphorylation.
AB  - Modulation of Ca2+ channels during repetitive activity in excitable cells can
      have an important role in altering cellular function. In mammalian
      parasympathetic and dorsal root ganglion neurons, L-type Ca2+ channels are
      potentiated by single depolarizing prepulses or trains of short high-frequency
      depolarizing pulses. This type of potentiation takes place regardless of whether
      Ca2+ or Ba2+ is the charge carrier and requires phosphorylation by a adenosine
      3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. The magnitude of
      facilitation was correlated with frequency of conditioning trains, was enhanced
      by 8-bromoadenosine 3',5'-cyclic monophosphate or the Sp diastereomer of
      adenosine 3',5'-cyclic monophosphothioate (cAMPS), and reduced by Rp-cAMPS or a
      peptide inhibitor of cAMP-dependent protein kinase. The N-type Ca2+ channels
      exhibited the opposite response to these agents. We propose that the potentiation
      of L-type Ca2+ channel currents in neurons is due to state-dependent
      phosphorylation by cAMP-dependent protein kinase (Sculptoreanu, A., T. Scheuer,
      and W. A. Catterall. Nature Lond. 364: 240-243, 1993; Sculptoreanu, A., E.
      Rotman, M. Takahashi, T. Scheuer, and W. A. Catterall. Proc. Natl. Acad. Sci. USA
      90: 10135-10139, 1993.). Thus state-dependent phosphorylation in neurons may be a
      mechanism for the regulation of various functions including transmitter release.

PMID- 7573404
TI  - IP3-activated Ca2+ channels in the plasma membrane of cultured vascular
      endothelial cells.
AB  - Although it is clear that D-myo-inositol 1,4,5-trisphosphate (IP3) plays an
      important role in the activation of Ca2+ influx, the mechanisms by which this
      occurs remain controversial. In an attempt to determine the role of IP3 in the
      activation of Ca2+ influx, patch-clamp single-channel experiments in the cell
      attached, inside-out, and outside-out configurations were performed on cultured
      bovine aortic endothelial cells (BAEC). The results presented indicate that both
      IP3 and intracellular Ca2+ can modulate the activity of a Ca(2+)-selective
      channel found in the plasma membrane of these cells. Addition of 10 microM IP3
      increased channel open probability (P(o)) from a control value of 0.12 +/- 0.05
      to 0.7 +/- 0.13 at a constant intracellular Ca2+ of 1 nM in excised inside-out
      patches. D-Myo-inositol 1,3,4,5-tetrakisphosphate at 50 microM was ineffective in
      altering channel P(o). Channel activity declined after approximately 2 min in the
      continuous presence of IP3. Three to four minutes after addition of IP3, channel
      P(o) was reduced from 0.7 +/- 0.2 to 0.2 +/- 0.1, indicating that an additional
      regulator might be required to maintain channel activity in excised patches. The
      channel was reversibly blocked by application of 1 microgram/ml heparin to the
      intracellular side of inside-out patches. This Ca(2+)-selective channel is
      indistinguishable from the depletion-activated Ca2+ channel we have previously
      described in BAEC.

PMID- 7573405
TI  - S-nitrosoglutathione reversibly inhibits GAPDH by S-nitrosylation.
AB  - Nitric oxide (NO), produced by vascular endothelial cells, mediates both
      physiological and pathological responses. Although the molecular targets
      responsible for NO-mediated endothelial cell injury are not known, one candidate
      is the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In
      this study, we investigated the mechanism involved in NO-mediated GAPDH
      inhibition and found that S-nitrosoglutathione (GSNO) inhibited GAPDH activity in
      both purified enzyme preparations and endothelial cells. Furthermore, GSNO
      mediated GAPDH inhibition occurred by modification of the active site cysteine
      residue in GAPDH, since increasing concentrations of the substrate,
      glyceraldehyde-3-phosphate, which interacts with the active site cysteine
      residue, protected GAPDH from inhibition by GSNO. Although under certain
      conditions both GSNO and the NO donor, sodium nitroprusside (SNP), led to the
      covalent NAD(+)-dependent modification of GAPDH, this putative ADP ribosylation
      was unlikely to be the primary mechanism for inhibition, since the stoichiometry
      was extremely low, and, in the case of GSNO, inhibition was completely reversed
      by thiol reagents. Furthermore, GSNO effectively S-nitrosylated GAPDH, and the
      extent of nitrosylation was linearly correlated with the degree of inhibition
      such that addition of 1 mole of NO per mole of GAPDH monomer was necessary to
      inhibit the enzyme. Consistent with this finding, GSNO-mediated GAPDH inhibition
      was reversible with low-molecular-weight thiols, and the reversal of inhibition
      correlated with the "denitrosylation" of GAPDH. These results suggest that
      endothelial GAPDH is a target for NO and that inhibition occurs principally by
      the reversible S-nitrosylation of the active site cysteine residue in GAPDH.

PMID- 7573406
TI  - Induction of NG-monomethyl-L-arginine uptake: a mechanism for differential
      inhibition of NO synthases?
AB  - The properties, selectivity, and regulation of NG-monomethyl-L-arginine (L-NMMA)
      uptake were examined in a human cultured vascular endothelial cell line SGHEC-7
      and murine macrophage J774 cells. In both cell types the uptake of L-[14C]NMMA
      was time and temperature dependent. In endothelial cells L-[14C]NMMA uptake
      occurred via a single saturable carrier-mediated system with an apparent Kt of 77
      +/- 2 microM. In murine macrophage cells a saturable component with an apparent
      Kt of 51 +/- 6 microM and a nonsaturable component of L-NMMA uptake were
      identified. In both cell types uptake of L-[14C]NMMA (10 microM) was
      significantly inhibited in the presence of 100-fold excess of L-NMMA, asymmetric
      NG,NG-dimethyl-L-arginine (ADMA), symmetric NG,NG-dimethyl-L-arginine (SDMA), L
      canavanine, L-arginine, and to a lesser extent D-arginine. Uptake of L-[14C]NMMA
      was inhibited weakly (approximately 30%) by NG-nitro-L-arginine, NG-nitro-L
      arginine methyl ester, aminoguanidine, and L-citrulline. Incubation of macrophage
      J774 cells with lipopolysaccharide (LPS; 1 or 10 micrograms/ml) resulted in the
      induction of nitric oxide (NO) synthase activity determined by the accumulation
      of nitrite in the culture medium. In these cells an enhanced uptake of L-NMMA
      uptake was observed which was prevented by pretreatment with cycloheximide (1
      microM) but not dexamethasone (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573407
TI  - Regulation of Ca(2+)-dependent nitric oxide synthase in bovine aortic endothelial
      cells.
AB  - Vascular endothelium responds to Ca(2+)-mobilizing agonists by producing nitric
      oxide (NO), a potent vasodilator and inhibitor of platelet aggregation.
      Regulation of constitutively expressed endothelial NO synthase (eNOS) in intact
      cells is not well understood. We investigated the kinetics of NO formation in
      response to Ca(2+)-mobilizing agonists, the requirement for extracellular L
      arginine, and the role of NO in regulating eNOS activity. When endothelial cells
      were stimulated with bradykinin and ATP in the presence of 100 microM L-arginine,
      we observed a rapid and transient rise in intracellular Ca2+ concentration
      ([Ca2+]i) from 50 +/- 8 nM to 698 +/- 74 and 637 +/- 53 nM, respectively, and a
      rapid and transient rise in NO production from a basal level of 37 pmol.min-1.mg
      protein-1 to 256 and 275 pmol.min-1.mg protein-1, respectively. When cells were
      stimulated with A-23187 or thapsigargin in the presence of 100 microM L-arginine,
      we observed a sustained increase in [Ca2+]i and a sustained increase in NO
      production. The rate of NO synthesis was linear over 30 min, rising above control
      levels of 7 pmol/min to 53 pmol/min for A-23187 and 62 pmol/min for thapsigargin.
      Thapsigargin stimulated NO production and [Ca2+]i with 50% effective
      concentration values of 0.01 and 0.05 microM, respectively. Ca(2+)-stimulated NO
      production was attenuated by the NO synthase inhibitor NG-monomethyl-L-arginine,
      the removal of extracellular L-arginine, and the Ca(2+)-chelator ethylene glycol
      bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When we exposed cells to
      NO gas (3.1 mM for 15 min) and S-nitrosoglutathione (10 mM for 1 h) thapsigargin
      stimulated NO production was decreased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573410
TI  - Maximum speed of shortening and ATPase activity in atrial and ventricular
      myocardia of hyperthyroid rats.
AB  - The kinetic properties of the myofibrillar system of atrial and ventricular
      myocardia of hyperthyroid rats were analyzed by determining ATPase activity and
      maximum shortening velocity. Hyperthyroidism was induced by daily subcutaneous
      injections of triiodothyronine (0.2 mg/kg body wt) for 2 wk. The treatment
      induced a marked atrial and ventricular hypertrophy and, in ventricular
      myocardium, an isomyosin shift toward a homogeneous V1 composition. Skinned
      trabeculae and purified myofibrils were prepared from atrial and ventricular
      myocardia. Enzymatic assays on the myofibrils showed that both Ca-stimulated
      ATPase activity and Ca-Mg-dependent ATPase activity had equal values in atrial
      and ventricular myocardia. In skinned trabeculae during maximal Ca activations,
      force-velocity curves were determined by load-clamp maneuvers, and unloaded
      shortening velocity (Vo) was obtained with the slack-test method. Both maximum
      shortening velocities extrapolated from the force-velocity curves (Vmax) and Vo
      were significantly higher (+68 and +52%, respectively) in atrial than in
      ventricular preparations. Developed tension was significantly greater in
      ventricular preparations. Maximum power output was not significantly different.
      Previous findings (V. Cappelli, R. Bottinelli, C. Poggesi, R. Moggio, and C.
      Reggiani. Circ. Res. 65: 446-457, 1989) had led to the conclusion that variations
      in ATPase activity and shortening velocity of ventricular myocardium can be
      accounted for by changes in isomyosin composition. In this light, the present
      results suggest that 1) ATPase activity is equal in atrial and ventricular
      myocardia as the two tissues contain the same myosin heavy chain isoform, 2) the
      difference in maximum speed of shortening between atrium and ventricle might be
      due to the presence of tissue-specific isoforms of myosin light chains.

PMID- 7573411
TI  - Whole cell sodium conductance of principal cells freshly isolated from rat
      cortical collecting duct.
AB  - Cortical collecting duct fragments were manually dissected from 6-wk-old Sprague
      Dawley rats. The fragments were enzymatically digested (collagenase A) into
      single cells, washed, and resuspended in serum-free RPMI 1640. Individual cells
      were examined electrophysiologically using the whole cell patch-clamp technique.
      Two morphologically distinct cell types were present in the cell suspension.
      Small round cells that had a capacitance of 7 pF and larger oval cells with a
      capacitance of 29 pF were consistently observed. Whole cell electrophysiological
      examination revealed that the small round cells had virtually no plasma membrane
      ionic conductance, whereas both inward and outward currents were observed in the
      larger oval-type cells. Also, superfusion of 250 pM arginine vasopressin
      specifically increased the inward conductance of only the larger cells. The
      effect could be completely inhibited by 2 microM amiloride or 100 mumol of the Rp
      diastereomer of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (a
      specific adenosine 3',5'-cyclic monophosphate inhibitor). These findings are
      consistent with the hypothesis that the larger cells are principal cells and the
      smaller cells are intercalated cells and directly demonstrate that an amiloride
      sensitive whole cell conductance is readily observable in freshly isolated
      cortical collecting duct cells. Thus the whole cell configuration of the patch
      clamp technique appears to be well suited for assessing cellular mechanisms that
      regulate the ionic conductances of cortical collecting duct cells.

PMID- 7573413
TI  - Head-down tilt increases rat cardiac muscle eIF-2 alpha phosphorylation.
AB  - We previously demonstrated that head-down tilt in rats decreases heart
      polypeptide initiation rate and proposed a mechanism whereby redistribution of
      the chaperone heat-shock cognate/heat-shock protein-70 (HSC/HSP-70) facilitates
      the phosphorylation of eukaryotic initiation factor-2 alpha (eIF-2 alpha). In
      this study, two-dimensional gel electrophoretic analysis of eIF-2 alpha showed no
      phosphorylation in control hearts. At 8 h of head-down tilt, there was a 45%
      increase in total eIF-2 alpha, and 79% was phosphorylated. At 18 h, eIF-2 alpha
      increased to 142% of control, of which 4% was phosphorylated. This is consistent
      with the previous study where, at 8 h, there was a 78% increase in polysomal
      HSC/HSP-70 and a shift in the polysome center-of-mass to lighter polysomes
      (indicating decreased initiation). After 18 h of suspension, polysomal HSC/HSP-70
      levels were 24% relative to control, and the center-of-mass returned toward
      control. We conclude that the decrease in polypeptide initiation during head-down
      tilt is mediated by HSC/HSP-70 via phosphorylation of eIF-2 alpha.

PMID- 7573408
TI  - ATP depletion inhibits capacitative Ca2+ entry in rat thymic lymphocytes.
AB  - The present study investigates the requirement for cellular ATP in the increase
      in plasma membrane Ca2+ permeability activated by the release of Ca2+ from
      intracellular stores in rat thymic lymphocytes (capacitative Ca2+ entry). The
      permeability state of this pathway following activation with thapsigargin was
      probed in control and ATP-depleted cells using fluorometric measurements of
      intracellular Ca2+, Mn2+ entry, and membrane potential, and unidirectional
      measurements of Ca2+ uptake using 45Ca2+. The capacitative Ca(2+)-entry pathway
      was markedly inhibited in cells depleted of ATP by incubation in glucose-free
      solution containing oligomycin, antimycin A, and 2-deoxy-D-glucose. These data
      cannot be explained on the basis of a loss of the transmembrane electrochemical
      gradient for Ca2+, alterations in intracellular pH or cellular Na+ content, a
      direct effect of the inhibitors of ATP production on the capacitative Ca(2+)
      entry pathway, or the ability of thapsigargin to release Ca2+ from intracellular
      stores. Rather, these data are consistent with a requirement for ATP or a high
      energy phosphate donor in the activation and/or maintained activation of
      capacitative Ca2+ entry.

PMID- 7573409
TI  - Localization and quantification of endoplasmic reticulum Ca(2+)-ATPase isoform
      transcripts.
AB  - The Ca(2+)-adenosinetriphosphatase pump of the sarcoplasmic or endoplasmic
      reticulum (SERCA) plays a critical role in Ca2+ signaling and homeostasis in all
      cells and is encoded by a family of homologous and alternatively spliced genes.
      To understand more clearly the role the different isoforms play in cell
      physiology, we have undertaken a quantitative and qualitative assessment of the
      tissue distribution of transcripts encoding each SERCA isoform. SERCA1 expression
      is restricted to fast-twitch striated muscles, SERCA2a to cardiac and slow-twitch
      striated muscles, whereas SERCA2b is ubiquitously expressed. SERCA3 is expressed
      most abundantly in large and small intestine, thymus, and cerebellum and at lower
      levels in spleen, lymph node, and lung. In situ hybridization analyses revealed
      SERCA3 transcripts in cells of the intestinal crypt, the thymic cortex, and
      Purkinje cells in cerebellum. In addition, SERCA3 was expressed abundantly in
      isolated rat spleen lymphocytes, in various murine lymphoid cell lines, and in
      primary cultured microvascular endothelial cells. This analysis demonstrates that
      SERCA3 is expressed selectively in cells in which Ca2+ signaling plays a critical
      and sensitive role in regulating physiological processes.

PMID- 7573412
TI  - Water channel-carrying vesicles in the rat IMCD contain cellubrevin.
AB  - Antidiuretic hormone (arginine vasopressin) induces a cyclic process of docking,
      fusion, and endocytosis of water channel-containing vesicles in the collecting
      duct. There is now evidence that docking and endocytosis are mediated by an array
      of proteins associated with vesicles and target membranes. In recent studies, we
      have shown that cellubrevin, a member of the vesicle-associated membrane protein
      family, as well as other docking proteins, are expressed in the rat inner
      medullary collecting duct. We now show by immunogold electron microscopy that
      cellubrevin is present on vesicles containing water channels, that it is
      associated with both coated and uncoated vesicles, and that it is present on the
      apical membrane. Cellubrevin, therefore, is in a position to mediate one or more
      steps in arginine vasopressin-induced water channel cycling.

PMID- 7573414
TI  - Lung epithelial Na channel subunits are differentially regulated during
      development and by steroids.
AB  - Because the alpha-subunit of the rat lung epithelial Na channel (rENaC) is not
      expressed until late fetal gestation, the developmental immaturity of alpha-rENaC
      may be involved in the premature fetal lung's inability to mount a Na-absorptive
      response to appropriate agonists. As previous work has shown that the beta- and
      gamma-rENaC subunits of the Na channel are required for maximal alpha-rENaC
      activity, we determined their developmental expression in the fetal lung. In
      addition, because thyroid and corticosteroid therapy can mature the in vivo fetal
      lamb lung's ability to transport Na, we wished to determine whether such
      treatment increased the expression of alpha-, beta-, and gamma-rENaC. Lungs were
      harvested from normal rat fetuses of 17 through 22 days gestation (term = 22
      days), normal rat pups during the first week of life, and adult rats. Initial
      expression of alpha-rENaC was detected at 19 days gestation and progressively
      increased in utero. beta- and gamma-rENaC mRNA were not detected until 21 and 22
      days gestation, and then only at very low levels. During the first week after
      birth, the levels of alpha-rENaC declined, whereas beta- and gamma-rENaC mRNA
      levels increased. This pre- and postnatal pattern of alpha-rENaC expression
      correlates with the endogenous glucocorticosteroid levels in the fetus and the
      rat pup's early postnatal corticosteroid resistance. Combined or separate
      treatment of pregnant rats (16 through 22 days gestational age) with thyroid
      releasing hormone (TRH) and/or dexamethasone (Dex) for 48 h showed that Dex, but
      not TRH, could increase fetal lung alpha-rENaC mRNA levels.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7573415
TI  - Conversion between permeability states of IP3 receptors in cultured smooth muscle
      cells.
AB  - The kinetics of the effect of inositol 1,4,5-trisphosphate (IP3) on Ca2+ in the
      sarcoplasmic reticulum (SR) were studied in saponin-permeabilized A7r5 cells. At
      0.1 microM, IP3 elicited slow monoexponential declines in SR free Ca2+
      concentration ([Ca2+]SR). For IP3 concentration ([IP3]) = 0.2-100 microM, evoked
      declines in [Ca2+]SR were biphasic and best fit as the sum of two first-order
      processes with rate constants kfast and kslow. The kfast varied as a function of
      [IP3] over the range tested, whereas kslow was already maximal when [IP3] = 0.1
      microM. To analyze SR Ca2+ release elicited by IP3, the rate constants for IP3
      induced changes in the total SR Ca2+ content (kR) were calculated. kR was
      accurately described only when both [Ca2+]SR and [IP3] were considered together.
      kR was dependent on IP3 binding to receptors that existed in either of two
      states, a high-affinity low-conductance state (IP3RH) and a low-affinity high
      conductance state (IP3RL). The permeability of IP3RL was 12.28 times larger than
      that of IP3RH, and the conversion between permeability states as well as changes
      in both the affinity and cooperativity with which IP3 was bound to IP3RL were
      mediated by SR Ca2+. This SR Ca(2+)-dependent modulation of the characteristics
      of IP3 receptors forms the basis for the biphasic time course characteristic of
      IP3-evoked SR Ca2+ release.

PMID- 7573418
TI  - Pentagastrin increases pepsin secretion without increasing its fractional
      synthetic rate.
AB  - We studied the effects of increasing doses of pentagastrin on gastric secretion
      of pepsin and on incorporation of L-[1-13C]leucine into gastric aspirate protein
      as an index of pepsin synthesis. Pentagastrin (0.25-4.0 micrograms.kg-1.h-1)
      significantly increased pepsin output from basal 76 mg/h to < or = 181 mg/h but
      did not significantly alter incorporation of L-[1-13C]leucine from the basal
      fractional synthetic rate of 3.63 +/- 0.05%/h. In four subjects in whom infusion
      of tracer leucine was continued for > 1 day, aspiration of pepsin between 24 and
      27 h demonstrated that plateau 13C labeling of leucine in pepsin had been
      attained, but at a value that was only 48% of the 13C labeling of plasma alpha
      ketoisocaproic acid (alpha-KIC) [0.730 +/- 0.02 (SE) vs. 1.520 +/- 0.14 atoms
      %excess]. This suggests that actual rates of pepsin synthesis were approximately
      double those calculated on the basis of alpha-KIC labeling. The results are
      consistent with an interpretation that increasing doses of pentagastrin cause
      increased secretion of pepsinogen by recruitment of gastric chief cells, each
      synthesizing pepsinogen at an unaltered rate. Plateau 13C enrichment of alpha-KIC
      may not be a valid surrogate for plateau 13C leucine enrichment when fractional
      synthetic rates of some secreted proteins are calculated.

PMID- 7573416
TI  - Proenkephalin gene regulation in the neuroendocrine hypothalamus: a model of gene
      regulation in the CNS.
AB  - During the past decade, a great deal of progress has been made in studying the
      mechanisms by which transcription of neuropeptides is regulated by second
      messengers and neural activity. Such investigations, which have depended to a
      great extent on the use of transformed cell lines, are far from complete. Yet a
      major challenge for the coming decade is to understand the regulation of
      neuropeptide genes by physiologically and pharmacologically relevant stimuli in
      appropriate cell types in vivo. The proenkephalin gene, a member of the opioid
      gene family, has served as a model to study regulated transcription, not only in
      cell lines, but also in central (e.g., hypothalamic) and peripheral (e.g.,
      adrenal) neuroendocrine tissues. Here we review regulation of proenkephalin gene
      expression in the hypothalamus. Several approaches, including in situ
      hybridization, use of transgenic mice, and the adaptation of electrophoretic
      mobility shift assays to complex tissues, have played critical roles in recent
      advances. A summary of possible future developments in this field of research is
      also presented.

PMID- 7573417
TI  - Interaction of decreased arterial PO2 and exercise on carbohydrate metabolism in
      the dog.
AB  - To determine the mechanism by which low arterial PO2 (PaO2) affects muscle
      carbohydrate (CHO) metabolism during exercise, dogs inhaled gas consisting of
      0.21 (NO; n = 6) or 0.11 (LO; n = 6) inspired oxygen fraction (FIO2) during rest
      and 150 min of moderate treadmill exercise. Limb arteriovenous difference and
      isotopic ([3H]- and [14C]glucose) methods were used to assess muscle carbohydrate
      metabolism: PaO2 was reduced by approximately 50% in LO vs. NO, but limb O2
      uptake was similar. Glucose disappearance was increased during rest (13 +/- 2 vs.
      19 +/- 1 mumol.kg-1.min-1) and exercise (23 +/- 4 vs. 36 +/- 6 mumol.kg-1.min-1
      at 150 min) in LO vs. NO, but arterial glucose was unchanged because hepatic
      glucose production was increased similarly. Limb glucose and pyruvate oxidation
      (derived from vein [14C]lactate specific activity) rates were elevated about
      twofold during rest and exercise in LO vs. NO. Estimated limb glycogenolysis
      increased at rest (21 +/- 9 vs. 96 +/- 23 mumol/min) and during exercise (70 +/-
      21 vs. 184 +/- 41 mumol/min at 150 min) in LO vs. NO. The %CO2 and %lactate from
      glucose in LO were about twofold the values in NO in rest and exercise. The %CO2
      from pyruvate was greater and free fatty acid levels were lower, suggesting
      reduced fat metabolism in LO. Arterial lactate and pyruvate levels were elevated
      during rest and the initial 30 min of exercise, even though net limb outputs were
      no greater. Lactate-to-pyruvate ratios and pH were similar in LO and NO during
      exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573419
TI  - Trophic effects of angiotensin II on neonatal rat cardiac myocytes are mediated
      by cardiac fibroblasts.
AB  - Cultured neonatal rat cardiac fibroblasts (NF) and myocytes (NM) were used to
      examine the distribution of angiotensin II (ANG II) receptors and the potential
      role of NF in mediating the trophic response to ANG II in the heart. In NM
      preparations cultured for 2-5 days, specific binding to 125I-ANG II was < 10% of
      the specific binding in cultured NF. Binding assays, immunocytochemistry, and
      autoradiography in NM cultured for > 5 days identified two populations of cells,
      one with fibroblast-like morphology and high density of ANG II receptors and
      another with low binding, comparable to NM cultures at day 5 or earlier.
      Conditioned medium (CM) from untreated NF increased cell surface area and net
      [3H]leucine (Leu) incorporation 1.4-fold in NM. CM from ANG II-treated NF
      enhanced [3H]Leu incorporation 2.2-fold in NM. This potentiating effect of ANG II
      was inhibited by losartan and was absent when ANG II was added directly to NM. In
      addition, studies using antibodies and bioassay for transforming growth factor
      beta 1 (TGF-beta 1) suggested that TGF-beta 1 does not mediate the trophic
      effects of ANG II on NM. We conclude that ANG II receptors are localized
      predominantly on NF and that ANG II can indirectly stimulate hypertrophy of NM by
      stimulating NF to produce a transferrable factor(s). These data suggest that
      cardiac fibroblasts may play a critical role in mediating the hypertrophic
      response to ANG II in the rat heart.

PMID- 7573420
TI  - Mechanotransduction in bone: role of strain rate.
AB  - Bone tissue can detect and respond to its mechanical environment, but there is no
      consensus for how bone cells detect mechanical loads. Some think that cells sense
      tissue deformation (strain) and respond when strain is abnormally high. However,
      strains in bone tissue are usually very small, and it is questionable whether
      bone cells are sensitive enough to detect them. Another theory suggests that
      mechanical loads are coupled to the bone cells by stress-generated fluid flow
      within the bone tissue, which is dependent on the rate of change of bone strain.
      We applied bending loads to the tibiae of adult rats to create equivalent peak
      strains in the bone tissue but with varied rates of strain. Bone formation was
      significantly increased in the two experimental groups when the highest strain
      rates were compared with lower strain rates (P < 0.01), and the amount of new
      bone formation was directly proportional to the rate of strain in the bone
      tissue. These results suggest that relatively large strains alone are not
      sufficient to activate bone cells. High strain rates and possibly stress
      generated fluid flow are required to stimulate new bone formation.

PMID- 7573421
TI  - Estimation of glucose-alanine-lactate-glutamine cycles in postabsorptive humans:
      role of skeletal muscle.
AB  - To evaluate transfer of carbon between plasma glucose and plasma alanine (glucose
      alanine cycle) and lactate (Cori cycle), to assess the contribution of skeletal
      muscle to these cycles, and to determine whether a glucose-glutamine cycle exists
      in postabsorptive humans, we infused 11 normal overnight-fasted volunteers with
      [2-3H]glucose, [6-14C]glucose, and [3-13C]alanine to isotopic steady state and in
      7 of these simultaneously measured forearm net balance, uptake, and release of
      labeled and unlabeled glucose, lactate, and alanine. We found that 40.9 +/- 3.3,
      66.8 +/- 3.2, and 13.4 +/- 1.1%, respectively, of plasma alanine, lactate, and
      glutamine carbon came from plasma glucose. More plasma glucose was converted to
      plasma alanine than could be derived from plasma alanine (1.89 +/- 0.20 vs. 1.48
      +/- 0.15 mumol.kg-1.min-1, P < 0.001). A similar direction of net carbon flux was
      found for lactate (8.5 vs. 4.2 mumol.kg-1.min-1), with only glutamine adding more
      carbon to plasma glucose than was received from it (1.0 vs. 0.75 mumol.kg-1.min
      1). Skeletal muscle accounted for 50.2 +/- 3.9 and 45.5 +/- 5.7% of the overall
      appearance of alanine and lactate in plasma and 54.2 +/- 5.4 and 36.4 +/- 4.2% of
      their respective origins from plasma glucose. Skeletal muscle release of alanine
      and lactate that had been formed from plasma glucose accounted for 19.1 +/- 2.1
      and 48.4 +/- 4.8%, respectively, of muscle glucose uptake and 42.4 +/- 5.5 and
      49.9 +/- 5.8% of the overall release of alanine and lactate from muscle.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573422
TI  - Tumor-related selection of calcium signals in vasopressin-stimulated human
      adenomatous corticotrophs.
AB  - The action of arginine vasopressin (AVP) on cytosolic free calcium concentration
      ([Ca2+]i) was studied at the single-cell level in corticotrophs cultured from
      pituitary adenoma fragments removed from eight patients with Cushing's disease.
      AVP evoked distinct [Ca2+]i responses with regard to the tumor origin. In cells
      from two tumors, AVP consistently evoked a series of characteristic elevations of
      [Ca2+]i (transient pattern) that depended on Ca2+ entry. In cells from the other
      tumors, AVP triggered different patterns of [Ca2+]i rise, which consisted of low
      amplitude slow monophasic increases at low AVP concentration and a high-amplitude
      spike increase followed by a sustained plateau (spike-plateau pattern) at higher
      concentration of AVP. Slow monophasic increases and the spike of spike-plateau
      responses were due to calcium release from internal stores, whereas the plateau
      was a consequence of calcium entry. These two patterns (transient vs. spike
      plateau) resemble those observed in subpopulations of corticotrophs from healthy
      rat pituitary glands (Corcuff et al., J. Biol. Chem. 268: 22313-22321, 1993),
      suggesting that tumorigenesis can lead in pituitary tissues to a selection rather
      than alteration of AVP [Ca2+]i signals.

PMID- 7573424
TI  - Role of glucagon in maintenance of euglycemia in fed and fasted rats.
AB  - The role of glucagon in the regulation of blood glucose in fed and fasted
      anesthetized rats was studied by injecting intravenously 4 ml/kg of a high
      capacity (40 nmol/ml) high-affinity (0.6 x 10(11) mol/l) monoclonal glucagon
      antibody. Blood glucose was lowered by the antibody by 2 mmol/l in fed rats but
      remained unchanged in 10- and 48-h-fasted rats. Antibody injection significantly
      reduced plasma insulin in both fed and 10-h-fasted rats. In 10-h-fasted rats,
      propranolol injection decreased blood glucose by 0.6 mmol/l, and combined with
      antibody administration, a decrease by 1.1 mmol/l was observed. Blood glucose was
      never < 3.3 mmol/l. Thus glucagon is partly responsible for maintenance of
      euglycemia in fed rats, whereas during fasting it plays a limited role. However,
      immunoneutralization of glucagon reduces insulin secretion irrespective of blood
      glucose. Additional mechanisms seem to be responsible for the maintenance of
      blood glucose in the fasting state when glucagon and the sympathoadrenergic
      system are blocked.

PMID- 7573423
TI  - Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in
      humans.
AB  - The regulation of the active form of pyruvate dehydrogenase (PDHa) and related
      metabolic events were examined in human skeletal muscle during repeated bouts of
      maximum exercise. Seven subjects completed three consecutive 30-s bouts of
      maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the
      vastus lateralis were taken before and immediately after each bout. PDHa
      increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11,
      and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and
      3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2
      and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate
      production and oxidation resulted in substantial lactate accumulation to 89.5 +/-
      11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in
      bout 3. These events coincided with an increase in the mitochondrial oxidation
      state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle
      lactate production during exercise was not an O2-dependent process in our
      subjects. During exercise the primary factor regulating PDHa transformation was
      probably intracellular Ca2+. In contrast, the primary regulatory factors causing
      greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased
      concentrations of pyruvate and H+. Greater PDHa during recovery facilitated
      continued oxidation of the lactate load between exercise bouts.

PMID- 7573425
TI  - Pulsatile insulin secretion accounts for 70% of total insulin secretion during
      fasting.
AB  - The purpose of the present study was to determine the contributions of discrete
      insulin secretory bursts vs. basal insulin release to total insulin secretion in
      vivo. Quantification of the partitioning of pulsatile and basal insulin secretion
      is complicated by physiological delivery of these pulses into the portal vein and
      the absence of validated methods of measuring the rates of pulsatile and basal
      insulin secretion in vivo. We therefore 1) developed a canine model with
      chronically implanted portal vein catheters, 2) validated an established
      deconvolution technique as well as a novel direct catheterization technique
      (Clustcath) for measurement of pulsatile and nonpulsatile insulin secretion rates
      in this model, and 3) applied these methods to study insulin secretion in the
      overnight-fasted dog in vivo to determine the contribution of pulsatile vs. basal
      insulin secretion to total rates of endogenous insulin secretion. Rates of total,
      pulsatile, and nonpulsatile endogenous insulin secretion measured by Cluscath
      closely parallel those measured by deconvolution analysis (54 +/- 15 vs. 51 +/-
      11, 38 +/- 12 vs. 36 +/- 11, and 16 +/- 4 vs. 14 +/- 4 pmol/min, respectively).
      Clustcath and deconvolution indicated that the majority of insulin was secreted
      as pulses (70 +/- 6 and 66 +/- 7%, respectively). These data infer that any
      process that selectively decreases the pulsatile component of insulin secretion
      (e.g., diabetes mellitus) will likely have a major impact on total insulin
      secretion.

PMID- 7573426
TI  - Diurnal rhythmicity of human cholesterol synthesis: normal pattern and adaptation
      to simulated "jet lag".
AB  - The diurnal rhythm of cholesterol synthesis was determined by deuterium
      incorporation from body water in five normolipemic men studied during a 24-h
      baseline period and on the 1st, 2nd, and 4th days of a simulated 12-h time zone
      shift achieved by delaying sleep times and, starting on the 2nd day, meal-times.
      Profiles of plasma cortisol and thyrotropin (TSH) were obtained simultaneously.
      Under baseline conditions, cholesterol synthetic rates varied from essentially
      zero in the morning to maximal values around midnight. On the 1st shifted day,
      this diurnal variation was unaltered despite sleep-wake reversal. The diurnal
      pattern of cholesterol synthesis, however, was shifted 5 h on the 2nd shifted day
      and approximately 12 h on the 4th. The diurnal variation of synthetic rate
      cholesterol fractional synthesis and plasma cortisol levels was negatively
      correlated on both the baseline day and the 1st shifted day. A positive
      correlation with the TSH rhythm was found on the 1st day only. During the 2nd and
      4th days, the rhythm of cholesterol synthesis adapted faster than the rhythms of
      cortisol and TSH. These findings indicate that cholesterol synthesis is not
      acutely entrained by the sleep-wake cycle nor is it primarily entrained by the
      circadian clock.

PMID- 7573427
TI  - Response of leucine metabolism to hyperinsulinemia under amino acid replacement
      in experimental hyperthyroidism.
AB  - We investigated the responsiveness of protein metabolism to insulin as a mediator
      of the protein catabolic response to hyperthyroidism in humans. Six healthy
      volunteers were studied in a postabsorptive state before and after oral intake of
      thyroid hormones (2 micrograms.kg-1.day-1 L-thyroxine for 6 wk along with 1
      microgram.kg-1.day-1 triiodothyronine for the last 2 wk). Insulin was infused at
      7.14 nmol.kg-1.min-1 for 140 min under euglycemic and eukalemic clamps. An
      appropriate amino acid infusion was used to blunt insulin-induced
      hypoaminoacidemia. Leucine kinetics were assessed using a primed continuous
      infusion of L-[1-13C]leucine. Hyperthyroidism induced a significant increase (P <
      0.05) in leucine endogenous appearance rate (a reflection of proteolysis; 2.15 +/
      0.06 vs. 1.76 +/- 0.03 mumol.kg-1.min-1 in the control state), oxidation (0.54
      +/- 0.04 vs. 0.47 +/- 0.07), and nonoxidative disposal (a reflection of protein
      synthesis; 1.80 +/- 0.06 vs. 1.45 +/- 0.06). Insulin lowered proteolysis. Further
      hyperthyroidism improved the ability of insulin to inhibit proteolysis, whether
      considered as an absolute decrease (-0.57 +/- 0.02 vs. -0.45 +/- 0.05 mumol.kg
      1.min-1, P < 0.05) or related to insulinemia [1.59 +/- 0.11 vs. 1.01 +/- 0.08
      mumol leucine.kg-1.min-1/(nmol insulin/l), P < 0.05]. Insulin also moderately
      (but significantly P < 0.05) lowered protein synthesis in both control and
      hyperthyroid states. These changes in insulin action may provide a mechanism to
      save body protein during hyperthyroidism.

PMID- 7573429
TI  - Measuring gluconeogenesis with [2-13C]glycerol and mass isotopomer distribution
      analysis of glucose.
AB  - We tested the validity of the use of [2-13C]glycerol and of the mass isotopomer
      distribution analysis of glucose for measuring gluconeogenesis in vitro and in
      vivo. When isolated rat livers (starved for 48 h) were infused with labeled
      glycerol without or with lactate+pyruvate, gluconeogenesis accounted for > 90% of
      glucose production. When glucose was added to the infusate so that glucose
      produced by the liver represented only 80 or 45% of total glucose output, this
      dilution could be calculated from the mass isotopomer distribution of glucose.
      When postabsorptive and starved rats were infused with [2-13C]glycerol,
      gluconeogenesis accounted for 54 +/- 2 and 89 +/- 1%, respectively, of glucose
      production. However, accurate measures could be obtained, particularly in
      postabsorptive rats, only with high tracer infusion rates (representing > or =
      50% of endogenous glycerol production rate). In both groups of rats, these
      infusion rates resulted in an increase in total glycerol turnover rate and
      gluconeogenesis from glycerol. In addition, hepatic concentration of glycerol 3
      phosphate was increased. In conclusion, [2-13C]glycerol infusion and mass
      isotopomer distribution analysis of glucose appear to be useful methods for
      studies of gluconeogenesis in vitro and in vivo; however, accurate measurements
      in vivo can be obtained only at the expense of some perturbation of the metabolic
      pathway studied.

PMID- 7573428
TI  - Quantification of incorporation of [15N]ammonia into plasma amino acids and urea.
AB  - The incorporation of 15N into individual plasma amino acids and urea was
      quantified in five human subjects who received 15NH4Cl either orally or
      intravenously for 6 h. After oral tracer administration, the highest enrichment
      was achieved by arginine, followed by urea and glutamine; distribution of 15N
      within glutamine was 55% amide and 45% amino N. Glutamine achieved the highest
      enrichment after the intravenous administration of tracer, with a distribution of
      92% amide and 8% amino N. The relative distribution pattern of 15N incorporation
      was quantified from the rate at which 15N initially appeared in each plasma
      component. Amino acids (especially arginine, glutamine, and glutamate) accounted
      for greater than one-half (54%) of the orally administered tracer that was
      initially recovered in plasma components, compared with 46% initial appearance
      for urea; for the intravenous tracer, amino acids accounted for 78% of initial
      appearance of tracer compared with 22% for urea. Our results highlight the
      involvement of the splanchnic bed in the utilization of orally administered
      ammonia (preferential incorporation of oral tracer into arginine, urea,
      glutamate, and the amino N of glutamine) in contrast to the preferential
      incorporation of systemically administered ammonia into the amide N of glutamine
      and alanine.

PMID- 7573430
TI  - Thromboxane A2-stimulated phospholipase D in osteoblast-like cells: possible
      involvement of PKC.
AB  - We examined the effect of thromboxane A2 (TxA2) on phosphatidylcholine
      hydrolyzing phospholipase D activity in osteoblast-like MC3T3-E1 cells. 9,11
      Epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of TxA2, stimulated
      the formations of both choline and inositol phosphates in a dose-dependent manner
      in the range between 10 nM and 10 microM. The formation of choline stimulated by
      a combination of STA2 and 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein
      kinase C-activating phorbol ester, was not additive. 1-(5-Isoquinolinyl-sulfonyl)
      2-methylpiperazine (H-7), an inhibitor of protein kinases, suppressed the
      formation of choline induced by STA2 as well as that by TPA, but 20 microM N-(2
      guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), a control for H-7 as a
      protein kinase C inhibitor, had little effect. Calphostin C, a potent and
      specific inhibitor of protein kinase C, also suppressed the formation of choline
      induced by STA2. The STA2-induced formation of choline was significantly reduced
      by chelating extracellular Ca2+ with ethylene glycol-bis(beta-amino-ethyl ether)
      N,N,N',N'-tetraacetic acid. STA2 dose dependently stimulated 45Ca2+ influx from
      extracellular space. STA2 stimulated DNA synthesis of MC3T3-E1 cells and
      increased the number of these cells. These results suggest that TxA2 stimulates
      phospholipase D in osteoblast-like cells, resulting in the direction of their
      proliferation, and that the activation of protein kinase C is involved in the
      stimulation of phospholipase D.

PMID- 7573433
TI  - Glutamate stimulates insulin secretion and improves glucose tolerance in rats.
AB  - We previously showed in vitro that glutamate stimulates insulin release via an
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Here we
      address a more physiological question concerning the in vivo effect of
      intravenously or orally administered glutamate on insulinemia and glycemia in fed
      and fasted rats. In anesthetized fed rats, the intravenous administration of
      glutamate at 9 and 30 mg/kg transiently increased insulinemia in a dose-dependent
      manner. The insulin-secretory effect of glutamate (9 mg/kg) was blocked by an
      antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
      In anesthetized fasted rats, glutamate at 9 mg/kg was ineffective, but during an
      intravenous glucose tolerance test (0.5 g/kg), glutamate markedly potentiated
      insulin release and increased the glucose disappearance rate. In conscious rats,
      the intragastric administration of glutamate at 200 mg/kg elicited a transient
      insulin response in fed animals and had no effect in fasted animals but, during
      an oral glucose tolerance test (1 g/kg), enhanced insulin secretion and reduced
      the hyperglycemia. Glutamate was effective at plasma concentrations of 200-300
      microM. In conclusion, intravenously and orally administered glutamate stimulates
      insulin secretion in vivo via an excitatory amino acid receptor and improves
      glucose tolerance.

PMID- 7573434
TI  - Glucose turnover in presence of changing glucose concentrations: error analysis
      for glucose disappearance.
AB  - The present studies were undertaken to determine whether 1) the cold- and hot
      GINF techniques used with Steele's model provide equivalent estimates of the
      rates of glucose appearance (R(a)) and disappearance (R(d)) in the presence of
      physiological changes in glucose and insulin concentrations, 2) the conditions
      for the best estimation of R(a) are the same as those for R(d), 3) the magnitude
      of error (if present) differs in diabetic and nondiabetic subjects, and 4)
      situations exist in which the knowledge of R(d) allows inferences to be made on
      whole body glucose uptake. To do so we performed experiments in non-insulin
      dependent diabetes mellitus and nondiabetic subjects using simultaneous infusions
      of [6-3H]glucose and [6-14C]glucose; glucose and insulin were infused to mimic
      normal postprandial glucose and insulin profiles; the infused glucose contained
      [6-14C]glucose but not [6-3H]glucose. Compared with the hot-GINF method, the
      traditional cold-GINF method underestimated (P < 0.05) R(a) and R(d) by 10-15%
      and hepatic glucose release by 25-50% during the 1st h of the study, with the
      magnitude of error being the same in both diabetic and nondiabetic subjects.
      Error analysis demonstrated that errors in R(a) and R(d) have different analytic
      expressions containing common structural but different volume errors. Both R(a)
      and R(d) can be accurately measured in diabetic and nondiabetic subjects if
      glucose specific activity is kept constant and the volume of the accessible pool
      is used to calculate glucose disappearance. The relationship between R(d) and
      whole body glucose uptake was also derived. Although R(d) can be determined by
      relying on measurements in the accessible pool only, the assessment of whole body
      glucose uptake requires a model of the nonaccessible portion of the glucose
      system. However, knowledge of R(d) can provide useful insights into the behavior
      of whole body glucose uptake.

PMID- 7573431
TI  - Nerve function and regeneration in diabetic rats: effects of ZD-7155, an AT1
      receptor antagonist.
AB  - Effects of the angiotensin II AT1 receptor antagonist ZD-7155 on nerve function,
      blood flow, capillarization, oxygenation, and regenerative capacity after injury
      were studied in streptozocin-diabetic rats. Deficits in saphenous sensory and
      sciatic motor conduction velocity measured after 1 or 2 mo of diabetes in
      anesthetized rats were prevented and corrected by ZD-7155. Sciatic resistance to
      hypoxic conduction failure, which was increased by 71% by 2 mo of diabetes, was
      attenuated by 39% with ZD-7155. Endoneurial capillary density, which was
      unaffected by diabetes, was increased by 34% with 2 mo of ZD-7155 treatment.
      Sciatic nutritive endoneurial blood flow, which was reduced by 45% by 2 mo of
      diabetes, remained in the nondiabetic range with ZD-7155. Mean endoneurial O2
      tension was reduced 38% by diabetes, which was attenuated by ZD-7155. Punctate
      freeze damage of sciatic nerve caused complete fiber degeneration. Fourteen days
      postlesion, there was a 26% deficit in myelinated fiber regeneration distance
      after 2 mo of diabetes, which was prevented by ZD-7155 treatment from diabetes
      induction. Thus alterations in the renin-angiotensin system contribute to the
      neurovascular etiology of nerve dysfunction in experimental diabetes.

PMID- 7573432
TI  - Distinguishable substrate pools for muscle glyconeogenesis in lactate
      supplemented recovery from exercise.
AB  - The formation of muscle glycogen from substrates other than glucose
      (glyconeogenesis) has now been demonstrated 1) from circulating lactate when this
      lactate is elevated and 2) from intramuscular substrate, which equilibrates with
      the products of local glucose metabolism but not with circulating lactate [Am. J.
      Physiol. 267 (Endocrinol. Metab. 30): E210-E218, 1994]. The purpose of the
      present studies was to examine the interaction of recovery from low-intensity
      exercise (4-h swim) and supplementation with exogenous lactate in determining the
      distribution of carbon flux between these two pathways for the glyconeogenic
      process in the gastrocnemius muscles. Ten protocols were defined using
      [14C]bicarbonate (no local incorporation into glycogen), [U-14C]lactate (tracks
      circulating lactate), and recycled [1-14C]glucose (tracks local substrate
      formation and glyconeogenesis). During recovery, lactate was infused to increase
      circulating concentrations 15- to 20-fold. Glucose and saline infusions during
      recovery were used as controls. The results indicate that prior exercise
      primarily promotes the local incorporation of recycled glucose label produced
      within the muscle into glycogen. Exogenous lactate stimulates the incorporation
      of circulating lactate into muscle glycogen. The contribution of the two
      substrate pools to glycogen synthesis appears to be additive, indicating the
      independence of muscle glycogenesis from these two sources.

PMID- 7573435
TI  - Glucagon increases urinary oxalate excretion in the guinea pig.
AB  - Factors that influence hepatic oxalate synthesis are poorly defined. Hormones are
      important regulators of hepatic metabolism and could potentially be involved. The
      effects of hyperglucagonemia were examined in guinea pigs injected with either
      saline or pharmacological doses of glucagon for 4 days. Glucagon treatment
      increased mean urinary oxalate excretion by 77% in male and 34% in female
      animals. The levels of hepatic peroxisomal enzymes involved in oxalate synthesis
      declined with glucagon treatment, but experiments with isolated peroxisomes
      indicated that oxalate synthesis in vitro was unaffected. Glucagon decreased
      hepatic alanine levels by 66%, lactate by 69%, and pyruvate by 73%, but glycolate
      and glyoxylate levels were unaffected. This decrease in alanine would
      substantially lower the activity of alanine-to-glyoxylate aminotransferase
      activity in vivo and make more glyoxylate available for oxalate synthesis. The
      decrease in lactate and pyruvate concentrations would stimulate the enzymatic
      conversion of glyoxylate to oxalate and may account for the increase in oxalate
      synthesis without an increase in glyoxylate concentration. These results
      demonstrate that hepatic oxalate synthesis is influenced by metabolic changes and
      that alterations in hepatic alanine, lactate, and pyruvate concentrations may be
      important elements.

PMID- 7573436
TI  - Synergistic interaction of glucose and neurohumoral agonists to stimulate islet
      phosphoinositide hydrolysis.
AB  - The interaction between neurohumoral agonists and glucose to stimulate
      phosphoinositide (PI)-specific phospholipase C (PLC) and insulin release was
      examined. In freshly isolated rat islets, maximal glucose (40 mM),
      cholecystokinin (CCK; 300 nM), or carbachol (CCh; 1 mM) stimulated PI hydrolysis
      6.5-, 9.8-, and 5.7-fold, respectively, above basal. The combination of glucose
      and CCK or of glucose and CCh, but not of CCK and CCh, synergistically increased
      PI hydrolysis 23.2- and 21.6-fold, respectively, indicating that these
      secretagogues activate PLC by distinct pathways and that there is an interaction
      between them. This synergy was maximal at physiological concentrations of
      stimulatory glucose (8-10 mM) and was paralleled by a marked synergistic
      stimulation of insulin secretion. The enhanced PI response was partially Ca2+
      dependent and may involve the activation of distinct isozymes of PLC, which we
      identify in islets. These studies demonstrate for the first time a unique and
      highly sensitive synergistic interaction between glucose and neurohumoral
      agonists to stimulate PI hydrolysis, and they suggest that enhanced PI hydrolysis
      is important in the potentiation of glucose- and neurohumoral-stimulated insulin
      secretion.

PMID- 7573437
TI  - Splanchnic and muscle metabolism during exercise in NIDDM patients.
AB  - To characterize splanchnic and muscle metabolism during exercise in non-insulin
      dependent diabetes mellitus (NIDDM), eight male nonobese patients and seven
      healthy control subjects (CON) were studied during 40 min of bicycle exercise at
      60% of maximal oxygen uptake. Biopsies were obtained from the quadriceps femoris
      muscle at rest and immediately after exercise. Arterial glucose concentration in
      NIDDM had declined by 10% (P < 0.01) at the end of exercise, whereas in CON it
      had risen by 21% (P < 0.05). Leg glucose uptake rose from 0.19 +/- 0.06 mmol/min
      at rest to 2.25 +/- 0.61 mmol/min at the end of exercise in NIDDM and from 0.13
      +/- 0.05 to 1.17 +/- 0.34 mmol/min in CON. Splanchnic glucose output increased
      from 0.52 +/- 0.06 to 2.37 +/- 0.26 mmol/min in NIDDM and from 0.79 +/- 0.12 to
      2.44 +/- 0.38 mmol/min in CON. Leg lactate output during exercise was twofold
      higher in NIDDM. Muscle contents of lactate and glycogen were similar in both
      groups at rest, whereas after exercise lactate tended to be higher (19.5 +/- 1.7
      vs. 12.7 +/- 5.9 mmol/kg dry wt) and glycogen lower (154 +/- 35 vs. 251 +/- 41
      mmol glucosyl units/kg dry wt) in NIDDM. Whole body respiratory exchange ratio
      during exercise was higher in NIDDM (0.84 +/- 0.02 vs. 0.78 +/- 0.02, P < 0.05).
      Exercise-induced changes in other muscle metabolites were similar in NIDDM and
      CON. These data indicate that the decline in blood glucose during exercise in
      nonobese NIDDM is due to enhanced peripheral glucose utilization rather than to
      an attenuated increase in splanchnic glucose output.

PMID- 7573438
TI  - Relationship between changes in body composition and insulin responsiveness in
      models of the aging rat.
AB  - Increased body weight (BW) is one of several confounding factors that may
      contribute to the development of insulin resistance in human aging. Therefore
      aging-associated increase in BW was determined by 3H2O in Sprague-Dawley (S-D, n
      = 40) rats and was highly correlated with increased lean body mass (LBM), fat
      mass (FM), and plasma insulin and free fatty acid (FFA) levels (r2 > 0.850, P <
      0.01 for all). Insulin (18 mU.kg-1.min-1) responsiveness (Rd; 270 +/- 10 mumol.kg
      LBM-1.min-1, P < 0.01) decreased by 17% between 2 and 4 mo but did not decline
      further at 14 mo. This decrease was inversely correlated with the increase in FM
      between 2 and 4 mo (r2 = 0.522, P < 0.05). The decline in Rd was accompanied by
      an approximately 20% decrease in glycolytic rate by 4 mo (P < 0.01) and in
      glycogen synthesis rate at 14 mo (P < 0.01) compared with 2-mo rats. Thus early
      impairment in intracellular glucose metabolism occurred concomitantly with an
      initial, rapid, and disproportionate increase in FM compared with LBM. Further
      increases in FM after 4 mo of age were not associated with a further decrease in
      insulin responsiveness in either S-D or Fischer 344 aging rats.

PMID- 7573439
TI  - Inhibition of ACTH secretion blocks hypoxia-induced increase of adrenal cortical
      blood flow in fetal sheep.
AB  - To examine the role of endogenous adrenocorticotropic hormone (ACTH) in adrenal
      blood flow responses to hypoxia, we studied unanesthetized ovine fetuses during
      an intravenous infusion of cortisol or vehicle. Fetal hypoxia was induced after 5
      h of cortisol or vehicle infusion. Control fetuses were not made hypoxic. Blood
      flows were determined before and at three time points during the infusions. At 2
      and 6 h of hypoxia, in vehicle-infused fetuses, fetal plasma concentrations of
      immunoreactive ACTH (irACTH) had risen from 9 +/- 3 (SE) pg/ml to 68 +/- 25 and
      127 +/- 37 pg/ml, respectively. No significant change in fetal plasma irACTH
      occurred in the other groups. Adrenal cortical blood flow rose three- to fourfold
      during hypoxia in vehicle-infused fetuses but did not change from prehypoxia
      levels in cortisol-infused fetuses (P < 0.005). Medullary flow rose with
      hypoxemia, and this was not affected by concurrent cortisol infusion. Adrenal
      blood flows did not change in the control groups. Thus prior infusion of cortisol
      suppressed the rise in fetal plasma ACTH during hypoxia and selectively blocked
      the increase in adrenal cortical blood flow.

PMID- 7573442
TI  - Microinjection of TRH analogue into the dorsal vagal complex stimulates
      pancreatic secretion in rats.
AB  - Thyrotropin-releasing hormone (TRH) stimulates pancreatic exocrine secretion
      through the vagus nerve when injected into rat cerebrospinal fluid. However,
      little is known about the exact site of action of TRH in the brain to stimulate
      pancreatic secretion. Recent neuroimmunochemical and neurophysiological studies
      suggest that TRH could be a neurotransmitter in the dorsal vagal complex, which
      sends fibers to the pancreas through the vagus nerve. We therefore hypothesized
      that TRH may act centrally in the dorsal vagal complex to stimulate pancreatic
      exocrine secretion. To address this question, a TRH analogue, [1-methyl-(S)-4,5
      dihydroorotyl]-L-histidyl-L-prolinamide- NH2, was microinjected into the dorsal
      vagal complex, and basal pancreatic fluid flow and protein secretion were
      measured in urethan-anesthetized rats. Microinjection of TRH analogue (0.2-2
      ng/site) into the dorsal vagal complex significantly stimulated pancreatic flow
      and protein output in a dose-dependent manner. As a control, microinjection of
      the TRH analogue into the brain stem outside the vagal complex failed to
      stimulate pancreatic secretion. Either bilateral subdiaphragmatic vagotomy or
      atropine abolished the ability of the TRH analogue to stimulate pancreatic
      secretion. Our data suggest that TRH acts in the dorsal vagal complex to
      stimulate pancreatic secretion through vagus-dependent and cholinergic pathways.
      The dorsal vagal complex may play an important role as a central site for control
      of the exocrine pancreas.

PMID- 7573443
TI  - Continuous epithelial cell lines from ADPKD liver cysts exhibit characteristics
      of intrahepatic biliary epithelium.
AB  - We have produced continuous cell lines using retroviral transduction of SV40
      large T antigen into epithelial cells removed from the lumen of liver cysts from
      four female patients with autosomal dominant polycystic kidney disease (ADPKD).
      Liver cyst-derived epithelial (LCDE) cell lines are grown in a hormonally
      supplemented medium in the presence of lethally irradiated NIH/3T3 fibroblast
      coculture. LCDE cells maintain their epithelial appearance and are positive for
      the biliary-specific markers cytokeratin 7 and 19 and gamma-glutamyl
      transpeptidase while being negative for hepatocyte markers. SV40 large T antigen
      is localized to the cell nucleus. LCDE cells have been grown continuously for
      periods exceeding 12 mo and 25 passages (170 population doublings). LCDE cells
      exhibit intracellular pH regulatory pathways that, with one exception, are
      similar to those found in normal intrahepatic biliary epithelium. These LCDE cell
      lines exhibit impaired alkalinization in response to Cl- substitution. This
      finding is suggestive of decreased function or abundance of a Cl-/HCO3- anion
      exchanger and could account for the failure of ADPKD hepatic cysts to secrete
      HCO3- in response to secretin.

PMID- 7573441
TI  - Regulation of cholecystokinin secretion by intraluminal releasing factors.
AB  - Ingested nutrients stimulate secretion of gastrointestinal hormones that are
      necessary for the coordinated processes of digestion and absorption of food. One
      of the most important hormonal regulators of the digestive process is
      cholecystokinin (CCK). This hormone is concentrated in the proximal small
      intestine and is secreted into the blood on the ingestion of proteins and fats.
      The physiological actions of CCK include stimulation of pancreatic secretion and
      gallbladder contraction, regulation of gastric emptying, and induction of
      satiety. Therefore, in a highly coordinated manner CCK regulates the ingestion,
      digestion, and absorption of nutrients. The manner by which foods affect enteric
      hormone secretion is largely unknown. However, it has recently become apparent
      that two CCK-releasing factors are present in the lumen of the proximal small
      intestine. One of these factors, known as monitor peptide, has been chemically
      characterized. Monitor peptide is produced by pancreatic acinar cells and is
      secreted by way of the pancreatic duct into the duodenum. On reaching the small
      intestine, monitor peptide interacts with CCK cells to induce hormone secretion.
      A CCK-releasing factor of intestinal origin has been partially characterized and
      is responsible for stimulation of CCK secretion after 1) ingestion of protein or
      fats, 2) instillation of protease inhibitors into the duodenum, or 3) diversion
      of bile-pancreatic juice from the upper small intestine. Together, these
      releasing factors provide positive and negative feedback mechanisms for
      regulation of CCK secretion. This review discusses the physiological observations
      that have led to the chemical characterization of the CCK-releasing factors and
      the potential implications of this work to other hormones of the gastrointestinal
      tract.

PMID- 7573440
TI  - Thyroid hormone increases the partitioning of glucose transporters to the plasma
      membrane in ARL 15 cells.
AB  - The stimulation of glucose transport by 3,5,3'-triiodo-L-thyronine (T3) in the
      liver-derived ARL 15 cell line is only partly attributable to increased GLUT-1
      glucose transporter gene expression. To test the hypothesis that T3 increases the
      partitioning of GLUT-1 to the cell surface, we quantitated surface GLUT-1 using
      the photolabel ATB-[3H]BMPA. In control cells only approximately 20% of total
      cellular GLUT-1 was present at the cell surface. T3 treatment (100 nM) for 6 h
      increased the rate of 2-deoxy-[3H]glucose (2-DG) uptake by 30, 92, and 95% in
      three experiments and increased surface GLUT-1 photolabeling by 17, 81, and 72%,
      respectively, with no increase in total cellular GLUT-1. T3 treatment for 48 h
      increased 2-DG uptake by 143, 172, and 216% in three experiments and increased
      cell surface GLUT-1 photolabeling by 88, 161, and 184%, respectively, with
      smaller increases in total cellular GLUT-1. T3 treatment for 48 h thus increased
      the fraction of cellular GLUT-1 at the plasma membrane from 21 +/- 2 to 35 +/- 3%
      (SE). We conclude that most of the early (6-h) stimulation of glucose transport
      by T3 in ARL 15 cells is mediated by an increase in the partitioning of GLUT-1 to
      the plasma membrane. With more chronic T3 treatment (48 h), the enhanced surface
      partitioning of GLUT-1 is persistent and is superimposed on an increase in total
      cellular GLUT-1, accounting for a further increase in glucose transport.

PMID- 7573444
TI  - Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion.
AB  - Neural reflex pathways activated in response to mucosal stroking were
      investigated in segments of distal colon from guinea pigs. Stroking the mucosal
      surface of whole thickness or muscle-stripped segments with a brush at 1/s evoked
      an increase in short-circuit current (Isc) whose duration and amplitude were
      dependent on the number of strokes. The increase in Isc induced by mucosal
      stroking was virtually abolished by inhibitors of chloride secretion and by
      tetrodotoxin. The response was reduced by atropine, renzapride, and N-acetyl-5
      hydroxytryptophyl-5-hydroxytryptophan amide but not by mecamylamine, ketanserin,
      tropisetron, or SDZ-205-557. Mucosal application of 5-hydroxytryptamine and 5
      hydroxyindalpine increased Isc, which was attenuated by tetrodotoxin and
      renzapride. The results suggest that mucosal stroking evokes chloride secretion
      by activating neural reflex pathways utilizing serotoninergic receptors, of the 5
      HT1P class, as well as muscarinic receptors within the submucosal plexus.

PMID- 7573445
TI  - Novel model of integration of signaling pathways in rat pancreatic acinar cells.
AB  - Cholecystokinin (CCK) is the major pancreatic secretagogue and acinar cell
      mitogen. This study was performed to determine by which effector systems CCK
      regulates tyrosine kinases, phosphatidylinositol (PtdIns) 3-kinase, and
      phospholipase D (PLD) activities. Pancreatic acini loaded with [3H]myristic acid
      or [3H]inositol were used to assay PLD and PtdIns 3-kinase. G protein activation
      with NaF increased particulate and crude cytosolic tyrosine kinase and PLD
      activities. PLD activation was pertussis toxin sensitive. Inhibition of
      phospholipase C (PLC) slightly reduced caerulein-stimulated particulate tyrosine
      kinase and blocked crude cytosolic tyrosine kinase activity without affecting
      caerulein-induced PLD activity. Ca2+ is an important factor in caerulein
      stimulation of tyrosine kinase and PLD activities. Protein kinase C and tyrosine
      kinase inhibition abolished caerulein-activated particulate and crude cytosolic
      tyrosine kinase and PtdIns 3-kinase activities without any effect on PLD.
      Wortmannin inhibited PLD and PtdIns 3-kinase activation. Caerulein-induced
      amylase secretion was partially reduced by tyrosine kinase inhibition, with no
      effect from wortmannin. Caerulein can stimulate a pertussis toxin-insensitive G
      protein, leading to particulate tyrosine kinase activation and a Ca(2+)-sensitive
      cytosolic tyrosine kinase through PLC activation. However, PLD activation by
      caerulein is pertussis toxin sensitive, cytosolic Ca2+ sensitive, and independent
      of previous PLC and tyrosine kinase activation.

PMID- 7573446
TI  - Effects of ethanol, xylose, and glucose on canine jejunal motility.
AB  - Ethanol is an important source of calories that can cause certain
      gastrointestinal symptoms, notably diarrhea. To examine the effects of ethanol on
      the small bowel, we intraluminally perfused the jejunum of four dogs with ethanol
      (18, 9, 4.5, and 1.5%, wt/vol), D-xylose (30, 15, 7.5, and 4.5%, wt/vol), or
      glucose (30 and 5%, wt/vol). In other experiments, these solutes were infused
      intravenously. Saline was always given by the alternate route; jejunal manometry
      was recorded during and after the infusions. Phase III of the interdigestive
      cycle was delayed by all intraluminal infusions except for 4.5 and 1.5% ethanol,
      4.5% xylose, and 5% glucose. In addition, the onset of irregular contractile
      activity was delayed more with intraluminal ethanol than with intraluminal xylose
      or intraluminal glucose (P < 0.01). When administered intraluminally, ethanol and
      xylose appeared in blood but only ethanol equilibrated fully between the lumen
      and blood. Intravenous infusions of ethanol and xylose, but not glucose, also
      delayed the return of phase III. When given intravenously, ethanol and xylose
      were recovered from the lumen, whereas glucose never was. Ethanol and xylose had
      comparable effects on the canine small bowel; they induced prolonged periods of
      irregular contractile activity and delayed the return of phase III. These effects
      were seen rapidly when solutes were administered intraluminally and more slowly
      when they were given intravenously. These results suggest that local luminal
      mechanisms stimulated by solutes influence small bowel motility, and they imply
      that the gut recognizes solutes whether or not these molecules are metabolizable.

PMID- 7573448
TI  - Ca2+ currents in human colonic smooth muscle cells.
AB  - Voltage-gated Ca2+ currents were investigated in single smooth muscle cells
      freshly isolated from the circular layer of the human colon (ascending and
      descending portions) using the whole cell voltage-clamp technique. Tissue samples
      were obtained at the time of therapeutic surgery. In physiological salt solution
      (containing 2 mM Ca2+), an inward current was observed when the cell membrane was
      depolarized in the presence of tetrodotoxin. This current disappeared when Ca2+
      was removed from the bath solution and was inhibited when Ca2+ channel blockers
      were applied, indicating that the inward current was a Ca2+ current (ICa).
      Changing the holding potential (HP) from -100 mV to more positive potentials
      (e.g., -60 and -40 mV) markedly decreased the amplitude of ICa. The voltage
      dependence of steady-state activation and inactivation was represented by
      Boltzmann distributions; there was a substantial amount of overlap (window
      current) between -60 and -10 mV. A fast-inactivating ICa component followed by a
      slow-inactivating ICa component was observed in some cells from both ascending
      and descending colons. The fast ICa component was observed only when cells were
      held at -80 or -100 mV, and had a more negative threshold potential (-70 to -60
      mV). This component was sensitive to low concentrations of Ni2+ (30 microM) but
      was resistant to nifedipine (10-20 microM). In contrast, the slow (sustained) ICa
      component was observed at all HPs (-40 to -100 mV) and had a more positive
      threshold potential (about -40 mV). This component was insensitive to low
      concentration of Ni2+ but was sensitive to nifedipine and BAY K 8644.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573447
TI  - Modulation of smooth muscle contraction by sphingosylphosphorylcholine.
AB  - We have investigated the effect of sphingosylphosphorylcholine (SPC), a synthetic
      product that was implicated in the sphingomyelin cycle, and have assessed its
      role in intracellular signaling. SPC induced a dose-dependent contractile effect
      of smooth muscle cells isolated from the rectosigmoid of the rabbit. Maximal
      contraction occurred at 10(-6) M. The response started early, 25.4 +/- 6%
      shortening at 15 s, peaked at 30 s (32.5 +/- 2%), and remained sustained at 8 min
      (30.0 +/- 3.5%). Preincubation of the cells with thapsigargin had no effect on
      contraction induced by SPC. The response to a combination of threshold
      concentrations of inositol 1,4,5-trisphosphate (IP3) and SPC was additive and was
      significantly different from the maximal response elicited by each agent alone.
      SPC also induced activation of mitogen-activated protein kinase (MAP kinase).
      This study demonstrates that SPC is important in cellular signaling of
      gastrointestinal smooth muscle cells through a mechanism that is independent of
      IP3-sensitive calcium release and probably through activation of a protein kinase
      C-mediated activation of MAP kinase.

PMID- 7573449
TI  - Rhythmic electrical and mechanical activity in stomach of toad and frog.
AB  - Rhythmic slow spikes and contractions at 2-5/min occur in frog/toad stomach when
      longitudinal muscle is present, not in the circular layer after removal of the
      longitudinal layer. Interstitial cells of Cajal occur in frog stomach in the
      longitudinal layer and in toad stomach mainly in the longitudinal layer, with
      some between layers. They were identified by staining with methylene blue, the
      fluorescent dye rhodamine 123, toluidine blue, and by electron microscopy.
      Interstitial cells resemble in ultrastructure those observed in mammalian
      intestine by small cell diameter, long processes forming a network, large nuclei,
      mitochondria, caveolae, endoplasmic reticulum, and absence of fibrillae. Rhythmic
      activity in stomachs stained with methylene blue is abolished by bright
      illumination. Rhythmic slow spikes and contractions are reduced and frequency is
      lowered when Ca2+ concentration in the medium is significantly decreased; in high
      Ca2+ these functions are increased. Threshold concentration of Ca2+ for
      maintaining slow spikes was between 10(-7) and 10(-6) M Ca2+. Ba2+ and 2.5 mM
      increases slow spike frequency and amplitude; Ba2+ increases contractions
      proportionately more than spikes. Slow spikes are reduced or blocked by
      verapamil, nifedipine, and Cd2+ and are enhanced by BAY K 8644. Quaternary
      ammonium compounds tetraethylammonium and tetrapentyl-ammonium bromide prolong
      slow spikes and enhance contractions. Replacement of NaCl by LiCl, methyl
      glutamine, or treatment with amiloride reduces slow spike amplitude and to a
      lesser extent frequency. This indicates efflux of Ca2+ by Na+/Ca2+ exchange.
      Contractions, but not spikes, are reduced by the calmodulin blocker
      trifluoroperazine. Contractions are enhanced, but slow spikes are not altered by
      ouabain. This suggests retention of Ca2+ when a tonic Na+/K+ pump is blocked. A
      model for rhythmicity includes influx of Ca2+ via L-channels, repolarization by
      IKCa2+, efflux of Ca2+ by Na+/Ca2+ exchange, and efflux of Na+ by a Na+/K+ pump.
      Frequency is determined by rate constants for both influx and efflux of Ca2+.

PMID- 7573450
TI  - Reduced glutathione release into rat plasma by extrahepatic tissues.
AB  - The liver is the only tissue that has been demonstrated directly to secrete
      glutathione into the plasma. The present experiments were carried out to
      determine whether extrahepatic tissues secrete the reduced form of glutathione
      (GSH) as well. Phorone, a compound that depletes glutathione through glutathione
      S-transferase-dependent conjugation with GSH, was administered to fasted rats in
      a dose of 250 mg/kg. Two hours later, glutathione concentrations were reduced to
      the following: liver, 2%; plasma, 17%; and skeletal muscle, 63%. This showed that
      plasma and muscle glutathione were not depleted to the same extent as liver
      glutathione. Glutathione concentration in plasma from the hepatic vein was not
      higher than concentrations in plasma from the portal vein and from the aorta,
      indicating that the depleted liver was not releasing glutathione into the plasma.
      Total glutathione and GSH were higher in plasma from the femoral vein than in
      plasma from the aorta under these same conditions. This indicates that the leg
      releases GSH under conditions of absent hepatic GSH release when plasma
      glutathione concentrations are decreased. These results suggest that muscle
      secretes GSH into the extracellular space and raise the possibility that other
      tissues secrete GSH as well. Further studies will be required to determine
      whether GSH release by extrahepatic tissues is affected by the plasma glutathione
      concentration.

PMID- 7573451
TI  - Actions of Rab3 effector domain peptides in chief cells from guinea pig stomach.
AB  - Rab3 proteins are low molecular weight guanine nucleotide-binding proteins that
      belong to the Ras superfamily and are believed to play a role in the final steps
      of exocytosis. To examine potential interactions of these proteins with signaling
      pathways that mediate pepsinogen secretion from gastric chief cells, we
      synthesized peptides corresponding to the effector domain of Rab3. In the absence
      of added calcium [calcium concentration ([Ca2+]) < 1 nM], a maximal concentration
      (15 microM) of the Rab3 effector domain peptide or Rab3AL peptide, containing
      alanine and leucine substitutions, stimulated the release of 62 and 66%,
      respectively, of total pepsinogen from streptolysin O-permeabilized chief cells.
      A Rab2AL peptide, corresponding to the Rab2 effector domain, and modified
      (scrambled and truncated) Rab3AL peptides did not alter secretion from
      permeabilized cells. An additive secretory response was observed when 5 microM
      Rab3AL peptide was combined with increasing calcium ([Ca2+] < 1 nM to 3 microM).
      In contrast, adding up to 3 mM adenosine 3',5'-cyclic monophosphate (cAMP) had no
      effect on Rab3AL peptide-induced secretion, and Rab3AL peptide did not alter
      endogenous cAMP production. The addition of a nonhydrolyzable GTP analogue [0.01
      to 100 microM guanosine 5'-O-(3-thiotriphosphate)] potentiated the secretory
      response to Rab3AL peptide. This potentiated response indicates that other GTP
      binding proteins are involved in calcium-independent secretion. Preincubation of
      cells with streptolysin O (10-30 min), to allow egress of cytosolic constituents,
      enhanced the response to Rab3AL peptide, suggesting that the target(s) for this
      peptide is (are) anchored to chief cell membranes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7573452
TI  - Human colonic smooth muscle electrical activity during and after recovery from
      postoperative ileus.
AB  - Colon smooth muscle electrical control (ECA) and response activities (ERA) were
      recorded for up to 4 wk postoperatively for 48 patients after major abdominal
      operations. Bipolar electrodes were implanted into right and left colon circular
      muscle and exteriorized through the flanks, and signals were tape recorded for 2
      24 h daily beginning on the 1st postoperative day. A computer program was used
      for data reduction and analysis. Recorded signals were digitized and filtered.
      The ECA frequency components were identified by fast Fourier transformation, and
      their relative tenancy in low, mid, and high frequency ranges was determined.
      Short and long ERA burst duration and frequency and number and velocity of
      propagating long ERA bursts were determined. ECA was omnipresent and exhibited a
      downshift of the dominant frequency from the mid to the low range as recovery
      from postoperative ileus progressed. Concurrently, first in the right and then in
      the left colon, the frequency of long ERA bursts increased, followed by the
      appearance of propagating long ERA. After the 6th postoperative day, no further
      significant changes in parameters of colon electrical activity occurred with
      time.

PMID- 7573453
TI  - Gastrokinetic effects of erythromycin: myogenic and neurogenic mechanisms of
      action in rabbit stomach.
AB  - The aims of this study were to determine regional differences and the mechanism
      of gastric contractile effects of erythromycin. Rabbit gastric circular muscle
      strips were studied in vitro. The threshold dose for erythromycin was
      significantly less and the maximum contraction greater in the antrum (1 microM
      and 0.9 +/- 0.3 kg/cm2) than in the fundus (10 microM and 0.3 +/- 0.1 kg/cm2).
      Erythromycin-induced antral contractions were decreased by motilin tachyphylaxis
      but unaffected by tetrodotoxin, atropine, hexamethonium, or ondansetron. At a
      subthreshold dose (0.1 microM), erythromycin increased the frequency, but not the
      amplitude, of bethanechol (10 +/- 3%)-and substance P-induced (13 +/- 5%) phasic
      antral contractions. This chronotropic effect was inhibited with tetrodotoxin,
      atropine, or motilin tachyphylaxis. Erythromycin (10 microM) and motilin (1
      microM) enhanced the amplitude of substance P-induced tonic fundic contractions
      by 38 and 32%, respectively, without effect on bethanechol-induced contractions.
      In summary, erythromycin contracts antral muscle more potently and forcefully
      than fundic muscle. Erythromycin increases antral contractility by two
      mechanisms: an inotropic effect acting on smooth muscle motilin receptors, and,
      at lower doses, a cholinergic chronotropic effect mediated through neuronal
      motilin receptors.

PMID- 7573454
TI  - Impaired hepatocanalicular organic anion transport in endotoxemic rats.
AB  - To investigate the mechanism of sepsis-associated hyperbilirubinemia we have
      studied hepatocanalicular transport of organic anions in a rat model of
      endotoxemia. Rats were injected intravenously with lipopolysaccharides (LPS), and
      at different times after injection, canalicular transport of 2,4-dinitrophenyl-S
      glutathione (GS-DNP), as a model organic anion, was measured in perfused livers
      and isolated hepatocytes. In isolated liver perfusion experiments the initial
      biliary GS-DNP secretion rate was found to be significantly decreased 18 h after
      injection with 2 mg/kg LPS. In isolated hepatocytes from these rats, GS-DNP
      efflux rate was also significantly decreased (193.0 +/- 67 and 448.3 +/- 53
      nmol.min-1.g dry wt-1 in endotoxemic and normal hepatocytes, respectively).
      Inhibition of GS-DNP effluxin isolated endotoxemic hepatocytes was dose dependent
      and reached a maximum with 0.25 mg/kg LPS. Inhibition was maximal at 12 h after
      LPS injection. Transport activity gradually returned to normal in 4-5 days after
      endotoxemia was induced. Dexamethasone pretreatment partially reversed the
      inhibition of GS-DNP transport in isolated endotoxemic hepatocytes. The phorbol
      ester phorbol 12-myristate 13-acetate increased GS-DNP efflux by 73 +/- 16 and 24
      +/- 8% in endotoxemic and control hepatocytes, respectively, but could not
      restore the transport activity of endotoxemic hepatocytes to control levels.
      These results show that canalicular organic anion transport is decreased in the
      endotoxemic liver; this may play a role in the frequently observed
      hyperbilirubinemia during sepsis.

PMID- 7573455
TI  - High-affinity CCK receptors are coupled to phospholipase A2 pathways to mediate
      pancreatic amylase secretion.
AB  - It is well recognized that JMV-180, a cholecystokinin (CCK) analogue, acts as an
      agonist on the high-affinity CCK receptor in pancreatic acinar cells. It caused
      Ca2+ oscillations and amylase secretion in a manner independent of the
      phospholipase C-inositol 1,4,5-trisphosphate (IP3) pathway. We investigated the
      mechanism by which the high-affinity CCK receptor utilizes IP3-independent Ca2+
      signal transduction to mediate amylase secretion. JMV-180 (1-1,000 nM)-stimulated
      Ca2+ oscillations and amylase secretion were significantly inhibited by the
      phospholipase A2 (PLA2) inhibitor, ONO-RS-082 (10 microM). Using streptolysin O
      permeabilized cells, we showed that a porcine pancreatic anti-PLA2 antibody from
      rabbit serum (250 ng/ml) inhibited JMV-180-stimulated amylase secretion. In
      contrast to CCK octapeptide, JMV-180 (1 nM-10 microM) had no effect on
      intracellular IP3 levels. These concentrations of JMV-180 did, however, increase
      intracellular levels of arachidonic acid (AA) metabolite by 2.5-fold in a
      biphasic manner. Application of exogenous AA (10 microM) released 60% of ATP
      incorporated 45Ca2+ from permeabilized pancreatic acini within 3 min in a
      transient manner. We also showed that active phorbol ester (100 nM) inhibited
      Ca2+ oscillations and amylase secretion stimulated by JMV-180 (10 nM) or CCK-OPE
      (100 nM). Application of Mn2+ (2 mM) to superfused acini resulted in a rapid
      quench of fura 2 fluorescence during 10 nM JMV-180 stimulation, suggesting an
      involvement of extracellular Ca2+ influx. However, the major source of Ca2+
      utilized for oscillations during high-affinity CCK receptor activation was
      intracellular. In conclusion, we have demonstrated that the high-affinity CCK
      receptors are coupled to PLA2 pathways to produce AA, which mediates cytosolic
      Ca2+ oscillation and monophasic amylase secretion, in rat pancreatic acinar
      cells.

PMID- 7573456
TI  - Nerve growth factor synthesis by intestinal epithelial cells.
AB  - Nerve growth factor (NGF) exists in the gut of adult rats. The cells responsible
      for NGF synthesis in the gut remain unknown. IEC-6 and Caco-2 cells, established
      cell culture models of intestinal epithelial cells, were studied to determine
      whether intestinal epithelial cells, were studied to determine whether they
      synthesize and release NGF. Conditioned media from both IEC-6 and Caco-2 cells
      stimulated neurite outgrowth in both rat pheochromocytoma (PC-12) cells and
      sensory neurons derived from embryonic chick dorsal root ganglia (DRG). The
      addition of anti-NGF antibody blocked neurite outgrowth in PC-12 cells and
      partially blocked outgrowth in DRG cells. An NGF-enzyme-linked immunosorbant
      assay readily detected immunoreactive NGF in conditioned media from both cell
      lines, whereas cellular extracts from IEC-6, Caco-2, and isolated rat intestinal
      epithelial cells had low levels of immunoreactivity. Caco-2 monolayers primarily
      secreted NGF from the basolateral compartment, and interleukin-1 enhanced its
      secretion. IEC-6, Caco-2, and isolated rat intestinal epithelial cells expressed
      NGF mRNA as determined by reverse transcription polymerase chain reaction. These
      observations suggest that intestinal epithelial cells are capable of NGF
      synthesis.

PMID- 7573457
TI  - Bicarbonate diffusion through mucus.
AB  - The mucus layer overlying duodenal epithelium maintains a pH gradient against
      high luminal acid concentrations. Despite these adverse conditions, epithelial
      surface pH remains close to neutrality. The exact nature of the gradient-forming
      barrier remains unknown. The barrier consists of mucus into which HCO3- is
      secreted. Quantification of the ability of HCO3- to establish and maintain the
      gradient depends on accurate measurement of this ion's diffusion coefficient
      through mucus. We describe new experimental and mathematical methods for
      diffusion measurement and report diffusion coefficients for HCO3- diffusion
      through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion
      coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s,
      respectively. Modeling of the mucobicarbonate layer with this latter value
      suggests that for conditions of high luminal acid strength the neutralization of
      acid by HCO3- occurs just above the epithelial surface. Under these conditions
      the model predicts that fluid convection toward the lumen could be important in
      maintaining the pH gradient. In support of this hypothesis we were able to
      demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion
      of 0.15 N HCl in the rat duodenum.

PMID- 7573459
TI  - Differential display RT-PCR for identifying novel gene expression in the lung.
AB  - The unique identity of each cell is the result of differential gene expression. A
      new strategy for differential cDNA screening introduced by Liang and Pardee
      utilizes anchored oligo-dT primers and random 5' oligonucleotide 10-mers to carry
      out polymerase chain reaction (PCR) on reverse-transcribed RNA from different
      cell populations. The amplified cDNAs are displayed on a standard sequencing gel
      as 100-500 bands per lane on the resulting autoradiograms and comparisons are
      drawn between the different cell populations. The major advantages of this method
      over previous differential screening approaches are its high sensitivity, the
      small amounts of tissue required, and the ability to carry out rapid mRNA
      analyses using total RNA and to test multiple tissues in parallel. Its
      limitations are the need for many primer combinations for adequate representation
      of mRNAs and the large number of bands displayed. A screening strategy should
      include multiple positive and negative control samples and Northern blots to
      identify cDNAs differentially expressed. This approach should facilitate the
      identification of many novel genes expressed in a variety of physiological and
      pathological conditions.

PMID- 7573460
TI  - Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo
      under oxidative stress.
AB  - We studied the acute effects of cigarette smoke condensate (CSC), H2O2, and tumor
      necrosis factor (TNF)-alpha on the glutathione (GSH) redox system in a human type
      II epithelial cell line (A549) in vitro. CSC, in vitro and in vivo after
      intratracheal instillation of CSC in the rat, produced a depletion of
      intracellular soluble GSH, concomitant with GSH-conjugate formation, without
      significant elevation of oxidized GSH (GSSG), protein-GSH mixed disulfides
      (PrSSG), nor any GSH efflux from the cells. By contrast, H2O2 (500 microM) after
      5-min exposure to A549 cells caused significant depletion of intracellular GSH
      associated with an efflux of GSSG and a significant increase in the formation of
      PrSSG. TNF-alpha, in concentrations of 100 U/ml and 1,000 U/ml, produced a
      significant depletion of GSH in A549 cells after 4- and 24-h exposure, with an
      associated elevation of GSSG. The activities of glutathione peroxidase, gamma
      glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase were
      significantly decreased in epithelial cells and in rat lungs after CSC exposure,
      without change in glutathione S-transferase and glutathione reductase activities.
      By contrast, H2O2 and TNF-alpha did not alter these enzyme activities in
      epithelial cells. Thus GSH depletion and alteration in enzyme activities in
      alveolar epithelial cells by CSC, H2O2, and TNF-alpha occur by different
      mechanisms.

PMID- 7573458
TI  - cAMP regulates gastrin gene expression.
AB  - Gastrin is one of the most potent regulators of acid secretion and
      gastrointestinal cell growth. A variety of signals regulate gastrin release from
      the antral G cell. However, whether these secretagogues also stimulate gastrin
      gene expression has not been established. Dramatic increases in gastrin gene
      expression occur in the stomach after birth and in response to chronic
      achlorhydria. Moreover, gastrin gene expression in malignant islet cell tumors
      (gastrinomas) appears to represent reactivation of the fetal pattern of
      expression in the pancreas. Thus differential expression of the gastrin gene is a
      reflection of differences in transcriptional control. Since various luminal and
      humoral factors stimulate the production of cAMP and gastrin secretion in both
      gastrinoma and antral G cells, we studied the effect of cAMP on gastrin gene
      expression. Using stable and transient transformants of a pituitary cell line
      containing the human gastrin gene, we found that cAMP stimulates a three-fold
      increase in gastrin mRNA levels and that the response maps to elements located
      between -148 and -40 base pairs upstream from the cap site. Collectively, these
      studies link an important regulator of gastrin secretion to regulation of gastrin
      gene expression.

PMID- 7573461
TI  - Alterations in pulmonary artery tone during repeated episodes of hypoxia.
AB  - To examine the basis of pulmonary constriction during chronic hypoxia, rat
      pulmonary artery rings were precontracted and exposed to multiple episodes of
      hypoxia. The first hypoxic episode resulted in a transient contraction, followed
      by potent relaxation, and then a slow sustained contraction. Repeated hypoxic
      exposure resulted in stronger initial contraction and attenuated relaxation.
      Prolongation of the normoxic interval between hypoxic episodes reversed the
      attenuation of hypoxic relaxation. Pulmonary artery rings that were
      deendothelialized or treated with the nitric oxide synthesis inhibitor N omega
      nitro-L-arginine methyl ester or oxyhemoglobin displayed only hypoxic relaxation
      without initial or late contractions and no attenuation of relaxation during
      repeated hypoxia. Pretreatment of rings with indomethacin or adenosine or
      endothelin receptor antagonists had no effect on the hypoxia-mediated
      alterations. Thus repetitive exposure to hypoxia results in an increase in
      initial contraction and a decrease in relaxation of pulmonary artery rings.
      Frequency of hypoxic episodes and endothelial integrity determine pulmonary tone
      during repeated hypoxia. However, cyclooxygenase products, adenosine, or
      endothelin do not play a role in hypoxia-mediated changes in rat pulmonary artery
      tone.

PMID- 7573462
TI  - In situ localization of sodium-potassium ATPase mRNA in developing mouse lung
      epithelium.
AB  - The ontogeny of Na(+)-K(+)-adenosinetriphosphatase (ATPase) mRNA in the mouse
      lung was examined, using alpha- and beta-isoform-specific probes in Northern blot
      assays and for in situ hybridization analysis. Northern blot assays demonstrated
      an increase in Na(+)-K(+)-ATPase expression in the perinatal period, peaking at
      birth (D1), with alpha 1- and beta 1-isoform levels reaching six to eight times
      adult levels. In situ alpha 1-isoform hybridization signals were localized
      primarily to developing airway epithelium and were most intense on D1.
      Postnatally, alpha 1-isoform hybridization signals persisted in airway
      epithelium, although progressively diminishing in intensity relative to perinatal
      levels. In developing alveolar regions, alpha 1-isoform hybridization signals
      remained slightly above background during this period. beta 1-Isoform
      hybridization signals increased dramatically during the perinatal period in both
      developing airway and alveolar epithelia. Postnatally, beta 1-isoform
      hybridization signals declined slightly in airway epithelium and developed a
      punctate pattern in alveolar epithelium. These data indicate that the perinatal
      increase in Na(+)-K(+)-ATPase expression observed in the developing mouse lung is
      localized primarily to epithelial structures and is therefore likely to be
      related to the changes in transepithelial ion and fluid transport known to occur
      in the perinatal period.

PMID- 7573463
TI  - Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in
      inflammatory airway diseases.
AB  - The tachykinin neuropeptides substance P and neurokinin (NK) A have been
      postulated to participate in the inflammatory reaction in airways of smokers and
      asthmatics. We have examined the hypothesis that the expression of one or more of
      the three cloned tachykinin receptors (NK1, NK2, and NK3) is increased in
      inflammatory airway disorders, which could result in augmentation of the effect
      of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3
      receptor mRNA were detected by ribonuclease protection assay in RNA from both
      cartilaginous and membranous bronchi and subpleural lung. In lung samples
      containing membranous airways, NK2-receptor mRNA expression was increased
      fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor
      mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression
      was increased twofold in smokers without airflow obstruction compared with
      nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in
      patients with chronic obstructive pulmonary disease compared with smoking
      controls. In situ hybridization indicated NK1-receptor mRNA was expressed in
      submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3
      receptor mRNA were not detected. These observations have implications for the
      pathophysiology and treatment of both asthma and tobacco smoke-induced airway
      inflammation.

PMID- 7573464
TI  - Bleomycin induces apoptosis in human alveolar macrophages.
AB  - Bleomycin (BLM) is an effective antineoplastic drug; however, cumulative dosage
      is often associated with inflammation that can progress to pulmonary fibrosis.
      The mechanisms by which this occurs are not understood, but they have been
      proposed to involve the alveolar macrophage (AM). In this study, we examined the
      in vitro effects of BLM on human AM cytotoxicity and the role of heat shock
      proteins (HSP or stress proteins) in this process. Although BLM did not cause
      marked necrosis, it caused significant DNA fragmentation detected by in situ DNA
      labeling and confirmed by BLM-induced DNA ladder formation after 24 h. The DNA
      fragmentation was significantly blocked by 10 and 50 microM ZnCl2, suggesting
      that BLM was inducing apoptosis. BLM did not alter intracellular protooncogene
      bcl-2 or glutathione levels. However, BLM significantly (50%) blocked HSP-72
      expression by 4 h during a mild heat stress (39.8 degrees C). This inhibition
      occurs without affecting mRNA levels (in situ hybridization) for HSP-72 or
      overall protein synthesis ([35S]methionine incorporation), suggesting that BLM is
      blocking the stress response relatively specifically and post-transcriptionally.
      In summary, these results suggest that BLM causes apoptosis in human AM in vitro
      that is preceded by the inhibition of HSP-72 induction that appears to be caused
      by a posttranscriptional mechanism.

PMID- 7573466
TI  - Hydrogen peroxide contracts human airways in vitro: role of epithelium.
AB  - The effects of hydrogen peroxide (H2O2) on human airway smooth muscle tone were
      determined in vitro. Treatment with H2O2 led to transient concentration-related
      contractions in the organ bath, amounting to 118 +/- 14 mg (mean +/- SE; n = 12)
      at 1 mM H2O2, and to greater and more prolonged contractions under superfusion
      conditions, amounting to 451 +/- 71 mg (n = 17) at 1 mM H2O2. Epithelial removal
      augmented the response to H2O2 in both systems. Addition of catalase (500 U/ml)
      abolished the effects of H2O2. Pretreatment of superfused tissues with
      indomethacin (3 microM) shifted the concentration-effect curve to H2O2 rightward
      and almost abolished the response to 1 mM H2O2 in epithelium-intact preparations
      (n = 16; P < 0.05); the response in epithelium-denuded tissues was also
      significantly inhibited (n = 16; P < 0.05). Pretreatment of the tissues with the
      TP prostanoid-receptor antagonist GR-32191B (1 microM) also inhibited the
      contractile effect of H2O2 in epithelium-intact and -denuded tissues. In separate
      experiments, H2O2 resulted in concentration-related generation of prostaglandin
      (PG) D2 from isolated airway preparations. The amount of PGD2 released was not
      different in tissues with intact epithelium compared with those without (n = 9;
      NS). We conclude that H2O2 exerts on isolated human airways a contractile effect
      that is augmented by epithelium removal and is largely mediated by prostanoids.
      The source of PGD2 does not appear to be the epithelium, which we suggest serves
      mainly as a barrier against H2O2-mediated bronchoconstriction.

PMID- 7573465
TI  - Leukotoxin, 9,10-epoxy-12-octadecenoate inhibits mitochondrial respiration of
      isolated perfused rat lung.
AB  - To investigate how mitochondrial function was affected in leukotoxin (Lx)-,9,10
      epoxy-12-octadecenoate-induced lung injury, lung mitochondria were extracted from
      isolated perfused rat lung with or without Lx-induced edematous injury. In the
      lung treated with 30 mumol of Lx, the mitochondrial respiration rate in states 3
      and 4 significantly decreased (without mitochondrial uncoupling) concomitantly
      with increased release of lactate dehydrogenase (LDH), a parameter for cellular
      damage, into the perfusate and decreased ATP content in the lung tissue compared
      with those of untreated lung. Moreover, 30 mumol of Lx resulted in significant
      inhibition of cytochrome-c oxidase activity (vs. vehicle control). In contrast,
      lower doses of Lx (10 mumol) caused lung edema and cellular damage without
      evidence for mitochondrial dysfunction. We also examined cellular and
      mitochondrial damage in hydrostatic lung edema. Such edema showed neither
      suppressed mitochondrial respiration nor elevated LDH activity in perfusate,
      although lung wet weight increased as much as it did after 30 mumol Lx treatment.
      Our results suggest that the ex vivo mitochondrial dysfunction is one of the
      secondary (vs. initial augmented permeability) but specific manifestations of
      toxicity of Lx, and together with the previous reports, the ex vivo damaging
      effect of Lx against mitochondria may be ascribed not to its direct action on
      mitochondria but to Lx-derived cellular mechanism(s).

PMID- 7573467
TI  - Tachykinin regulation of airway smooth muscle cell proliferation.
AB  - The tachykinins, substance P (SP) and neurokinins A (NKA) and B (NKB), have been
      identified in the respiratory tract and implicated in mediating neurogenic
      inflammation of the airways. To the extent that these neuropeptides may be
      involved in the pathogenesis of asthma, a condition associated with hyperplasia
      of airway smooth muscle (ASM), we examined the mitogenic effects and mechanisms
      of action of tachykinins in cultured rabbit ASM cells. SP was found to elicit
      dose-dependent (10(-14) to 10(-4) M) stimulation of ASM cell proliferation, with
      a mean (+/- SE) maximal increase in cell number of 169 +/- 6.1% of control. In
      contrast, NKA and NKB had little and no effect on ASM cell growth, respectively.
      Because SP is nonselective in its binding to the tachykinin receptors, to
      identify the specific NK receptor subtype(s) mediating the promitogenic action of
      SP, in separate studies we found that 1) the NK1-receptor-specific agonist, [beta
      Ala4, Sar9, Met(O2)11]SP-(4-11) induced stimulation of ASM cell growth similar in
      magnitude to that elicited by SP; 2) in contrast, neither the NK1- nor NK2
      receptor-specific agonists, [beta-Ala8]NKA-(4-10) and [MePhe7]NKB, respectively,
      had any effect on ASM cell growth; and 3) the promitogenic action of SP was
      inhibited by the NK1-receptor antagonist, GR-82,334. Moreover, in extended
      experiments, we found that the phospholipase C and phospholipase A2 inhibitors,
      neomycin and quinacrine, respectively, each inhibited SP-induced ASM cell
      proliferation by approximately 45%. Collectively, these observations provide new
      evidence that the tachykinin SP induces ASM cell proliferation, and that this
      action is mediated by transmembrane signaling coupled to selective activation of
      the NK1 receptor.

PMID- 7573468
TI  - Keratinocyte growth factor increases mRNAs for SP-A and SP-B in adult rat
      alveolar type II cells in culture.
AB  - The production of pulmonary surfactant, a complex of phospholipids and lung
      specific surfactant proteins, is a primary function of alveolar type II cells.
      Although previous studies have demonstrated a role for cell-extracellular matrix
      interactions and normal cell shape in the maintenance of differentiated function
      in primary cultures of adult rat type II cells, a positive role for growth
      factors in surfactant protein gene expression in isolated normal adult type II
      cells has not been reported. In the present study, we have examined the effects
      of a panel of hormones, growth factors, and cytokines on the expression of mRNAs
      for surfactant proteins A, B, and C (SP-A, SP-B, and SP-C). Our results show that
      keratinocyte growth factor (KGF) induced a two- to threefold increase in steady
      state levels of mRNAs for SP-A and SP-B, but had no effect on or decreased SP-C
      mRNA. The increase in SP-A mRNA was accompanied by an increase in SP-A protein.
      The effects of KGF were both dose and time dependent, and they could be
      neutralized by a monoclonal antibody against KGF. The effects of KGF were
      mimicked by acidic fibroblast growth factor, which will bind the KGF receptor. We
      conclude that KGF can support differentiation of alveolar type II cells as well
      as act as a mitogen, thus suggesting an important role for KGF in maintenance of
      the alveolar epithelium.

PMID- 7573470
TI  - Composition of human airway mucins and effects after inhalation of acid aerosol.
AB  - Characterization of normal airway mucus is required to elucidate mechanisms
      protecting the airways and to understand changes associated with disease and
      environmental insult. Toward this goal, we collected bronchial washes (10 ml
      saline) from healthy human subjects to 1) evaluate the yield of high-density
      material (delta > or = 1.35 g/ml), and 2) characterize glycoconjugates associated
      with collected secretions. Samples were lipid extracted followed by CsCl density
      gradient centrifugation. The yield of high-density material from individual
      subjects was variable but sufficient to demonstrate that mucin glycoproteins are
      a major constituent of mucus from healthy airways and that proteoglycans are
      absent. Next, we investigated whether inhalation of H2SO4 aerosol (1,000
      microgram/m3), an environmental insult associated with alterations in mucociliary
      clearance, changes the composition of high-density glycoproteins in airway
      secretions. In a paired, double-blinded study, high-density fractions of
      bronchial secretions from 12 subjects were collected 18 h after exposures of 2 h
      to aerosolized NaCl and H2SO4. In all cases the high-density material displayed
      characteristics of mucin glycoproteins. In addition, a unique 150-kDa
      glycoprotein was detected in most but not all samples and may represent a small
      mucin glycoprotein differentially expressed in humans. No differences were noted
      between the two exposure conditions in the profiles of the glycoproteins or
      proteins after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Statistically, large changes with acid exposure in the composition of
      carbohydrates and amino acids were absent. Thus no substantial systematic changes
      in airway mucin glycoproteins or closely associated proteins and glycoproteins
      were correlated with H2SO4 exposure. Alternatively, statistical analysis of the
      differences between exposures in glycoprotein constituents among subjects denoted
      greater variability in carbohydrates compared with amino acids with repeated
      sampling, suggesting normal daily variations in the mucin composition of
      individual airway mucus.

PMID- 7573471
TI  - Electrophoretic analysis of contractile proteins of the diaphragm in chronically
      hypoxic rats.
AB  - We questioned whether the relative composition of the diaphragm proteins [myosin
      heavy chain (MHC), actin, tropomyosin (TM)-alpha and TM-beta, and MHC isoforms]
      was altered by chronic hypoxia. Rats were exposed to hypobaric hypoxia (inspired
      O2 pressure approximately 95 mmHg) from birth for 60 days or 9-11 mo. From the
      muscle homogenate, relative protein content was computed by densitometric
      analysis after protein separation with polyacrylamide gel electrophoresis and
      identification by immunoblotting. The relative concentrations of MHC, actin, TM
      alpha and TM-beta did not differ from those of control rats for either duration
      of exposure. The main MHC isoforms (I, IIa, IIb, IIx) remained unaltered after 60
      days but changed significantly after 9 mo of hypoxia, mostly because of a
      decrease in the slow (I) component and an increase of II complex. We conclude
      that chronic hypoxia of long duration modifies the expression of MHC isoforms in
      the rat diaphragm. Qualitative similar changes also occurred in a muscle of the
      thigh, the rectus femoris; hence, the changes in diaphragm MHC probably reflected
      the systemic effects of hypoxia rather than the increased mechanical load imposed
      by the chronic hyperventilation.

PMID- 7573469
TI  - Mechanisms of hypoxic vasodilation in ferret pulmonary arteries.
AB  - To investigate the mechanism of hypoxic pulmonary vasodilation we measured
      isometric tension in rings from ferret third- to fifth-generation intrapulmonary
      arteries mounted in organ baths (37 degrees C, 28% O2-5% CO2). After
      precontraction with phenylephrine (PE), hypoxia caused a brief transient
      vasoconstriction followed by marked vasodilation. Endothelial denudation did not
      affect the steady-state response. In vessels without endothelium, inhibition of
      cyclooxygenase and nitric oxide synthase had no effect on the response to
      hypoxia. Inhibition of ATP-dependent K+ channels (KATP) with glibenclamide,
      linogliride, or tolbutamide had no effect on normoxic tone before PE or the
      vasoconstrictor response to PE but inhibited hypoxic vasodilation. Inhibition of
      Ca(2+)-activated K+ (KCa) channels with charybdotoxin potentiated the
      vasoconstrictor response to PE but had no effect on hypoxic vasodilation. The
      nonspecific K(+)-channel inhibitor tetraethyl-ammonium (TEA) potentiated the
      response to PE and inhibited hypoxic vasodilation. Glibenclamide plus TEA
      inhibited hypoxic vasodilation more than either agent alone, suggesting that TEA
      inhibited the KATP-channel independent vasodilation. These results suggest that
      in isolated ferret pulmonary arteries hypoxia causes vasodilation partially by
      activating smooth muscle KATP channels. Activation of a TEA-sensitive channel
      that is not a KATP or KCa channel may also contribute to hypoxic vasodilation.

PMID- 7573472
TI  - Bronchial epithelial cells regulate fibroblast proliferation.
AB  - Chronic bronchitis frequently leads to irreversible airway obstruction.
      Alteration of airway architecture with abnormal airway connective tissue is
      thought to play an important role in this process. We hypothesized that the
      epithelial cells that line the airways modulate the development of peribronchial
      fibrosis and fixed airway obstruction by directing fibroblast proliferation. To
      assess this, we examined stimulatory activities for human lung fibroblast
      proliferation in bovine bronchial epithelial cell-conditioned medium. The
      conditioned medium stimulated the proliferation of fibroblasts in a serum-free
      culture system in a concentration-dependent manner. The fibroblast growth
      stimulatory activity was heterogenous, with molecular masses of > 50 and
      approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained
      fibroblast growth inhibitory factors, including both transforming growth factor
      (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF
      beta appeared to contribute to the morphological change of fibroblasts induced by
      the conditioned medium. Co-culture of human lung fibroblasts with bronchial
      epithelial cells resulted in a stimulation of fibroblast proliferation. In
      summary, airway epithelial cells appear to regulate fibroblast proliferation and
      may play a role in peribronchial fibrosis in chronic bronchitis.

PMID- 7573473
TI  - Effects of sodium concentration on human neutrophil bactericidal functions.
AB  - What are the ionic requirements for neutrophil (PMN) function and how might
      altered electrolyte concentrations contribute to airway disease? The in vitro
      killing of Pseudomonas aeruginosa by human peripheral white blood cells (WBCs)
      was progressively compromised Na+ concentration was lowered from 124 to 62 mM; at
      62 mM Na+, bactericidal activity was 28.8 +/- 7.4% (SE) of normal. In contrast,
      Cl- concentration affected killing only when lowered to 8 mM. We examined
      phagocytosis and oxidative metabolism in response to P. aeruginosa or particles
      opsonized with either immunoglobulin G (IgG) or complement (C'). Phagocytosis of
      P. aeruginosa and of IgG-coated particles was Na(+)-dependent (31.2 +/- 3.1 and
      58.6 +/- 14.2% of normal, respectively, at 62 mM Na+). However, no effect on
      uptake of C'-coated particles was observed, and the respiratory burst at 70 mM
      Na+ was normal regardless of stimuli. Thus low Na+ concentration compromises
      select PMN functions. These results may help explain why airways of cystic
      fibrosis (CF) patients become colonized with bacteria such as P. aeruginosa.
      Perhaps the low concentration of Na+ reported for some CF respiratory secretions
      inhibits bactericidal functions of PMNs, predisposing these patients to airway
      infections.

PMID- 7573475
TI  - Location of focal silver staining at endothelial gaps in inflamed venules
      examined by scanning electron microscopy.
AB  - The century-old histological technique of silver nitrate staining has proven to
      be extremely useful for visualizing endothelial cell borders and localizing
      endothelial gaps, but the significance of the staining is still not fully
      understood. To gain some insight into what silver nitrate stains, we developed a
      method that enabled us to use scanning electron microscopy with backscattered and
      secondary electron imaging to examine silver staining at endothelial cell borders
      of venules of the rat tracheal mucosa. We found that in normal venules, silver
      lines followed the smooth contour of cell borders. However, 1 min after
      endothelial permeability was increased by substance P, cell borders were
      irregular and displaced from the silver lines by as much as 4.3 microns, and the
      lines were accompanied by three types of silver deposits. Most common (46% of
      total) were annulus-shaped silver deposits that surrounded endothelial gaps.
      These deposits averaged 1.5 microns in width, were positioned symmetrically
      across cell borders, and were located at a depth of 0.3 micron beneath the
      luminal surface. Many endothelial gaps were partitioned into multiple pores
      (mean, 2.4) by fingerlike processes of endothelial cells. Surprisingly, the gaps
      occupied only 5.4% of the total area of the silver deposits and constituted 0.15%
      of the luminal surface of the leaky postcapillary venules. A second type of
      silver deposit (19% of total) was positioned asymmetrically with respect to the
      cell border and marked sites where endothelial cell margins still overlapped but
      appeared to be vertically separated by obliquely oriented gaps. A third type
      marked gaps at three-cell junctions; these were no more abundant than deposits
      elsewhere around the cell perimeter, suggesting that three-cell junctions were
      not unusually leaky sites. We conclude that silver nitrate marks endothelial cell
      borders and outlines endothelial cell gaps by staining an element of
      intercellular junctions. The annular shape of many silver deposits around gaps
      suggests that junctional elements in the apposing cells are separated during gap
      formation but are still present at the gap perimeter.

PMID- 7573474
TI  - Pulmonary cytochrome P-450 monooxygenase system and Clara cell differentiation in
      rats.
AB  - Because a number of studies suggest that the developmental expression of
      cytochrome P-450s (CYP) in Clara cells is species specific, this study was
      designed to compare the developmental patterns of the isoform CYP2B and NADPH
      reductase protein expression and CYP2B activity with the time course of smooth
      endoplasmic reticulum (SER) formation in Clara cells of rat lung. Pulmonary CYP2B
      activity measured as pentoxyresorufin O-dealkylation in lung homogenates was not
      detectable before 7 days postnatal age, but was detectable at adult levels at 50
      days postnatal age. In Clara cells, CYP2B and NADPH reductase were detected
      immunohistochemically at 4 days postnatal age and at adult levels at 10 days
      postnatal age. The volume density of SER in Clara cells of terminal bronchioles
      measured morphometrically increased significantly with postnatal age. We conclude
      that in the rat 1) CYP2B and NADPH reductase distribution and CYP2B activity are
      age dependent; 2) the increase in Clara cell SER precedes the expression of CYP2B
      protein; 3) cellular appearance of CYP2B protein precedes CYP activity; and 4)
      SER appearance and P-450 protein expression do not occur uniformly in
      differentiating Clara cells, even within the same bronchiole.

PMID- 7573476
TI  - Expression of transforming growth factor-beta type II receptor in rat lung is
      regulated during development.
AB  - Transforming growth factor-beta (TGF-beta) is an autocrine/paracrine growth
      factor that regulates cell proliferation, differentiation, extracellular matrix
      production and various other cell functions in the lung. TGF-beta exerts its
      effects on cells by binding to transmembrane heteromeric serine-threonine kinase
      receptors. The expression and localization of specific TGF-beta receptors in the
      lung, however, have not yet been investigated. In the present studies, we
      isolated a 1,762-base pair cDNA containing the full-length coding sequence for
      TGF-beta type II receptor (T beta RII) from rat fetal lung with the use of
      polymerase chain reaction methods. The expression of T beta RII during lung
      development was examined by Northern analysis. A 5.1-kilobase T beta RII mRNA was
      detected in rat lung tissue. T beta RII mRNA was expressed in rat fetal lung
      tissue early in development, increased as development proceeded, reached maximal
      concentration postnatally, and then decreased to the adult level. The
      localization of T beta RII in fetal and postnatal rat lung tissue was
      investigated with the use of in situ hybridization performed with an antisense
      RNA probe. T beta RII gene was expressed in the mesenchymal tissue and in the
      epithelial lining of the developing airway at day 16 of gestation. The
      hybridization signal of T beta RII mRNA was also observed in the adventitial
      layer of small blood vessels. Expression of T beta RII gene in the developing
      airway epithelium occurred along a proximal-distal gradient. In postnatal lung, T
      beta RII mRNA was detected mainly in parenchymal tissues and blood vessels.
      Expression of T beta RII remained high in the interstitium of interalveolar
      septa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573477
TI  - Effect of pH on potassium and proton conductance in renal proximal tubule.
AB  - The effect of intracellular and extracellular pH on potassium conductance (GK)
      was examined in isolated amphibian (Rana pipiens) proximal tubule cells under
      whole cell voltage clamp conditions. Internal perfusion of the patch pipette was
      used to precisely control intracellular pH. In the region of normal resting
      potential (-51 +/- 3 mV), raising cell pH from 6.5 to 8.0 did not significantly
      increase GK (1.1 +/- 0.3 vs. 1.3 +/- 0.3 nS; P > 0.08, n = 8). Similar elevations
      in external (bath) pH had even less of an effect on GK. In contrast, when cells
      were voltage clamped to 30 mV more negative than the resting potential, raising
      internal pH from 6.5 to 8.0 did increase GK from 1.05 +/- 0.3 to 1.8 +/- 0.5 nS
      (P < 0.04; n = 8). These results suggest that modest changes in pH have little
      effect on GK, except at large negative potentials. In the process of examining
      the pH dependence of GK, a slowly activating, voltage-dependent conductance of
      7.5 +/- 1 nS (n = 20; for 20 microns cells) was observed during cell
      depolarization. Although the instantaneous current-voltage relation of this
      conductance was linear, its marked voltage dependence produced an apparent steady
      state rectification, with Gm = 0.5 +/- 0.2 nS and Gout = 9.0 +/- 1 nS (n = 11).
      Outward current was reversibly blocked by 3 mM Cu, Cd, or Co. In the absence of
      Na, K, and Ca (and only trace amounts of Cl), rapid changes in bath pH from 6.5
      to 8.0 shifted the steady-state reversal potential (Erev) by -37 +/- 4 mV (n = 9)
      and the instantaneous Erev by -56 +/- 4 mV (n = 9). These shifts in Erev were
      consistent with a hydrogen ion conductance (GH), similar to what has been
      reported for snail neuron, neutrophils, alveolar epithelial cells, and
      phagocytes. Since the magnitude of this GH would be insignificant at resting cell
      pH and membrane potential, its role in renal proximal tubule under normal
      conditions is somewhat obscure. Nonetheless, in pathological situations, GH could
      function to prevent acid overload during any process that depolarizes the cell,
      such as low temperature or metabolic inhibition.

PMID- 7573478
TI  - P2 purinoceptor stimulation attenuates PTH inhibition of phosphate uptake by a G
      protein-dependent mechanism.
AB  - Purinergic P2 receptors are present on proximal renal tubules, but their function
      is unknown. Because P2 agonists antagonize vasopressin-stimulated water transport
      in the distal tubule by inhibiting activation of adenylyl cyclase, we postulated
      that P2 receptor activation blocks parathyroid hormone (PTH) inhibition of
      phosphate uptake in proximal tubule by preventing PTH-stimulated adenosine 3',5'
      cyclic monophosphate (cAMP) generation. PTH inhibition of sodium-dependent
      phosphate uptake was attenuated by alpha,beta-methylene-ATP (AMP-CPP), a P2x
      receptor agonist, but not by 2-methyl-thio-ATP, a P2y receptor agonist, in a dose
      dependent manner. AMP-CPP did not attenuate inhibition of phosphate uptake
      produced by direct activation of adenylyl cyclase with forskolin, by addition of
      the cAMP analogue 8-bromo-cAMP, or by inhibition of cAMP phosphodiesterase with
      RO-20-1724. Additionally, AMP-CPP had no effect on basal or PTH-stimulated cAMP
      production. As PTH also stimulates protein kinase C activation, the effect of AMP
      CPP on inhibition of phosphate uptake stimulated by phorbol 12-myristate 13
      acetate (PMA) was tested. AMP-CPP had no effect on PMA-induced inhibition of
      phosphate uptake. Pretreatment with pertussis toxin abolished the attenuating
      effect of AMP-CPP on PTH inhibition of sodium-dependent phosphate uptake. We
      conclude that activation of purinergic P2 receptors attenuates the inhibitory
      effect of PTH on sodium-dependent phosphate uptake by a G protein-dependent
      mechanism that is independent of cAMP generation protein kinase A activation, or
      protein kinase C activation.

PMID- 7573479
TI  - Frequency domain of renal autoregulation in the conscious dog.
AB  - The dynamic range in which renal blood flow (RBF) autoregulation occurs was
      determined in eight conscious foxhounds chronically catheterized in the abdominal
      aorta and implanted with a transit-time flow probe over the renal artery.
      Sinusoidal driving pressures (amplitude of 10 mmHg) were forced on the renal
      arterial pressure at different frequencies by a servo-control device, and
      transfer functions were calculated. Only one frequency range was found below
      which the gain of the transfer function declined and in which the phase angle
      increased (n = 8). This indicates the presence of a potent mechanism for renal
      autoregulation in the examined frequency range between 0.0031 and 0.08 Hz, which
      buffers changes in blood flow < 0.02 Hz. After furosemide treatment, one
      indicator for autoregulation (phase shift of transfer function) was significantly
      blunted at low frequencies (n = 6). Furosemide, however, did not reduce the phase
      shift to zero, suggesting that some autoregulation still remained in the
      frequency range between 0.04 and 0.08 Hz. In conclusion, autoregulation of RBF
      during sinusoidal changes in driving pressure between 0.0031 and 0.02 Hz is
      mediated by a single mechanism, which can be blocked by the acute administration
      of furosemide. The residual phase shift between arterial pressure and RBF in the
      transfer function observed during sinusoidal changes in driving pressure between
      0.04 and 0.08 Hz suggests the presence of a second mechanism for RBF
      autoregulation.

PMID- 7573481
TI  - Tubulointerstitial injury and impaired renal function after recovery from acute
      puromycin nephrosis.
AB  - Renal function was assessed at 2 and 8 wk after infusion of puromycin into the
      left renal artery of Munich Wistar rats. At 2 wk, albumin excretion averaged 90
      +/- 12 micrograms/min in the left kidney and 4 +/- 1 microgram/min in the right
      kidney. Unilateral nephrosis was accompanied by reduction in the glomerular
      filtration rate (GFR) (left, 0.71 +/- 0.04; right, 1.31 +/- 0.02 ml/min) and by
      impaired excretion of sodium (FENa; left, 0.025 +/- 0.004; right, 0.064 +/-
      0.006%). Reductions in GFR and FENa in the nephrotic kidney were not reversed by
      acute angiotensin II receptor blockade with losartan. At 8 wk, albumin excretion
      averaged 6 +/- 1 in the left kidney and 8 +/- 1 microgram/min in the right
      kidney. Recovery from nephrosis was accompanied by persistent reduction in GFR
      (left, 1.05 +/- 0.05; right, 1.41 +/- 0.05 ml/min) and impairment of sodium
      excretion in the previously nephrotic left kidney (left, 0.031 +/- 0.004; right,
      0.051 +/- 0.004%). Losartan again did not return GFR and FENa toward normal. The
      reductions in GFR and FENa in the previously nephrotic left kidney were
      associated with structural changes, including intratubular casts, an increased
      fractional volume of the interstitium (left, 25 +/- 1; right, 15 +/- 1%),
      decreased fractional volume of tubules (left, 66 +/- 2; right, 77 +/- 1%), and
      glomerular collapse (left, 15 +/- 2; right, 1 +/- 1%). These findings suggest
      that tubulointerstitial injury can cause persistent reduction in GFR and
      impairment of sodium excretion after recovery from acute nephrosis.

PMID- 7573480
TI  - Chemokine gene expression in anti-glomerular basement membrane antibody
      glomerulonephritis.
AB  - Chemokines may be important in the pathogenesis of glomerular leukocyte
      infiltration in antiglomerular basement membrane (GBM) antibody (Ab)
      glomerulonephritis (GN). We studied the expression of the C-C chemokines
      [macrophage inflammatory protein (MIP)-1 alpha, monocyte chemotactic protein
      (MCP)-1, and RANTES] and C-X-C chemokines [platelet factor 4 (PF4), interferon
      inducible protein of 10 kDa (IP-10), MIP-2, and cytokine-induced neutrophil
      chemoattractant (CINC)] at 30 min, 3, 6, 9, 15, and 24 h after induction of
      heterologous-phase anti-GBM Ab GN in Lewis rats. There was a rapid induction of
      CINC, MIP-2, MCP-1, and MIP-1 alpha mRNAs in the glomeruli of nephritic rats 30
      min after administration of the anti-GBM Ab, whereas increases in PF4 and IP-10
      mRNAs were not seen until 3 h. The mRNA expression of PF4, MIP-1 alpha, MIP-2,
      and IP-10 peaked at 3 h, whereas CINC and MCP-1 peaked at 6 and 15 h,
      respectively. By comparison, the expression of RANTES mRNA in rats with anti-GBM
      Ab GN did not differ from those of control rats. These changes in chemokine gene
      expression were associated with glomerular polymorphonuclear leukocytes (PMN) and
      monocyte/macrophage infiltration which peaked at 3 h (20.8 +/- 11.1
      PMN/glomerulus) and 24 h (8.2 +/- 1.0 ED-1 cells/glomerulus), respectively. The
      administration of dexamethasone suppressed glomerular chemokine mRNA expression
      (60-98%) at both 3 and 15 h, which was associated with a 50-100% reduction in
      glomerular PMN and monocyte/macrophage infiltration, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573482
TI  - Stimulation of proximal convoluted tubule phosphate transport by epidermal growth
      factor: signal transduction.
AB  - The present study investigated the signal-transduction pathway responsible for
      the epidermal growth factor (EGF) stimulation of phosphate transport (JPhos) in
      the rabbit proximal convoluted tubule (PCT). Genistein, 10(-4) M, bath and lumen,
      an inhibitor of EGF receptor tyrosine kinase activity, blocked the EGF effect on
      JPhos, consistent with a role for tyrosine kinase in the signal-transduction
      pathway. Both staurosporine (5 x 10(-8) M) and calphostin C (10(-8) M),
      inhibitors of protein kinase C, blocked the EGF stimulation of JPhos, indicating
      that protein kinase C is involved in EGF signaling. Intracellular calcium (Ca2+i)
      concentrations were measured in perfused tubules using fura PE3 to determine
      whether changes in Ca2+i were also part of the signaling pathway. After addition
      of 3 nM EGF, there was no change in Ca2+i, suggesting that stimulation of protein
      kinase C is not from phosphatidylinositol hydrolysis by phospholipase C-gamma. To
      determine whether phospholipase A2 (PLA2) is involved, the inhibitor mepacrine
      was used. Mepacrine (5 x 10(-5) M) had no direct effect on PCT transport but
      blocked the stimulatory effect of EGF on JPhos. PLA2 activity, assessed as free
      arachidonic acid release from proximal tubules in suspension, increased by 18.8%
      with 3 nM EGF. Thus the stimulation of JPhos by EGF is mediated via a signal
      transduction pathway involving tyrosine kinase, protein kinase C, and PLA2.

PMID- 7573484
TI  - Regulation of ATP-sensitive K+ channel by membrane-bound protein phosphatases in
      rat principal tubule cell.
AB  - The role of membrane-bound protein serine/threonine phosphatases (PP) in
      modulating the renal ATP-sensitive K+ (KATP) channel was examined using the patch
      clamp technique in principal cells of rat cortical collecting duct. In the
      absence of ATP, channel activity rapidly (11.2 s) declines (channel "rundown")
      upon excision of the membrane patches into control bath solutions (1 mM Mg2+,
      Ca2+ free). Both orthovanadate (5 mM), a broad-spectrum inhibitor of phosphatases
      except for Ca(2+)-dependent PP (PP-2B), and okadaic acid (OA, 1 microM), a potent
      inhibitor of PP types 1 and 2A (PP-1 and PP-2A), significantly slowed channel
      rundown. Removal of Mg2+ from the bath also slowed the rundown process.
      Incubation of cells with OA in the absence of Mg2+ or with orthovanadate in ATP
      free solution maintained channel activity at levels of approximately 70% of
      control values for 3 min after membrane excision. In contrast, Ca2+ (0.1 mM) and
      calmodulin (1 microM) in the presence of 1 mM Mg2+, a condition in which PP-2B is
      stimulated, had no significant effect on the channel activity that persisted in
      the presence of OA and orthovanadate. Application of exogenous PP-2A (1 U/ml) to
      the cytosolic side of membrane in inside-out patches significantly inhibited
      channel activity to 35.0% of control, but the inhibitory-effects of PP-1 (1 U/ml)
      and PP-2B (20 micrograms/ml) were minor. These results suggest that rundown of
      the renal KATP channel after membrane excision results mainly from
      dephosphorylation of the channel or an associated protein by membrane-bound
      phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573483
TI  - In situ hybridization of H-K-ATPase beta-subunit mRNA in rat and rabbit kidney.
AB  - Through a variety of techniques, several investigators have demonstrated the
      presence of an H-K-adenosinetriphosphatase (H-K-ATPase) enzyme in the renal
      collecting duct, suggesting that this enzyme serves an important physiological
      role in the regulation of acid-base balance and potassium excretion by the
      kidney. The present study was designed to localize cells expressing H-K-ATPase
      beta-subunit mRNA in rat and rabbit kidney by nonradioactive in situ
      hybridization. A 570-bp DNA fragment of rabbit renal H-K-ATPase beta-subunit was
      used to produce digoxigenin-labeled riboprobes by in vitro transcription.
      Northern blot hybridization demonstrated transcripts in rat gastric oxyntic
      mucosa and kidney. In situ hybridization on kidney tissue sections demonstrated H
      K-ATPase beta-subunit mRNA localization in epithelial cells, including
      intercalated cells in the connecting segment and cortical and medullary
      collecting duct, principal cells in the inner stripe of the outer medullary
      collecting duct, and inner medullary collecting duct cells in both the rat and
      the rabbit. These observations provide evidence that H-K-ATPase beta-subunit mRNA
      is present throughout the collecting duct of the kidney. The distribution of this
      message is consistent with a role for H-K-ATPase in bicarbonate absorption in
      both the outer and inner medullary collecting duct.

PMID- 7573486
TI  - Biphasic effect of angiotensin II on intracellular sodium concentration in rat
      proximal tubules.
AB  - Intracellular Na+ concentration ([Na+]i) was determined using ratiometric
      measurement of the Na(+)-sensitive fluorescent probe, sodium-binding benzofuran
      isophthalate (SBFI). Angiotensin II (ANG II, 10(-11)-10(-7) M), applied to the
      basolateral membrane of rat isolated proximal convoluted tubules, induced a rapid
      and reversible dose-dependent increase in [Na+]i, which was initiated within 300
      ms. A maximal response was observed over the range 10(-9)-10(-7) M ANG II, with
      an average increase in [Na+]i of 7.4 +/- 1.0 mM. At higher concentrations (10(-6)
      10(-5) M) ANG II decreased [Na+]i compared with control (14.2 +/- 0.6 mM). The
      increase in [Na+]i induced by 10(-9) M ANG II was attenuated by inhibiting the
      Na+/H+ antiporter with clonidine, whereas HOE-694, a specific blocker of the NHE
      1 isoform of the Na+/H+ exchanger, had no effect. The increase in [Na+]i induced
      by 10(-9) M ANG II was enhanced by inhibition of the Na(+)-HCO3- cotransporter
      with hydrogen-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, with an average
      increase in [Na+]i of 17.1 +/- 6.6 mM. The data provide direct, high time
      resolution measurements of the effects of ANG II on [Na+]i in the proximal tubule
      and support the proposition that an increase in transepithelial Na+ reabsorption
      by ANG II involves stimulation of both an Na+/H+ exchanger and the Na(+)-HCO3-
      cotransporter.

PMID- 7573485
TI  - Differential expression of multiple glutaminase mRNAs in LLC-PK1-F+ cells.
AB  - LLC-PK1-F+ cells are porcine proximal tubule-like cells that have been used to
      model the renal ammoniagenic response to metabolic acidosis. A 3.2-kb porcine
      glutaminase (GA) cDNA (pGA201) containing 528 bp of coding sequence and 2.7 kb of
      3'-untranslated region was cloned and sequenced. Probes derived from both porcine
      and rat GA cDNAs were used to characterize the expression of putative GA mRNAs in
      LLC-PK1-F+ cells. Two larger putative GA mRNAs (approximately 5.0 and 4.5 kb in
      length) were resolved and a smaller 2.5-kb species was also observed. The level
      of the 5.0-kb mRNA is detectable in freshly split LLC-PK1-F+ cells and increases
      as the cells reach confluence. In contrast, the amount of the 4.5-kb GA mRNA is
      greatest in freshly split cells and decreases gradually as the cells approach
      confluence. The levels of the 5.0- and 2.5-kb mRNAs are also affected by
      refeeding the cells, and the 2.5-kb mRNA accumulates to high levels if cells are
      retained in the same media for 4 days. Exposure to acidic media had little or no
      effect on the levels of GA mRNAs expressed in confluent or postconfluent cells,
      whereas, in growing and undifferentiated cells, this treatment did affect the
      level of the 4.5-kb mRNA. Thus the putative GA mRNA species are differentially
      expressed. Given this complexity, a careful assessment of GA mRNA species, of
      basal expression, and of growth conditions are essential for a meaningful
      analysis of GA mRNA levels in cultured cells.

PMID- 7573487
TI  - Anion secretion drives fluid secretion by monolayers of cultured human polycystic
      cells.
AB  - We have investigated the hypothesis that active anion transport drives fluid
      secretion by the cystic epithelium in autosomal dominant polycystic kidney
      disease (ADPKD). We prepared monolayers of a primary culture derived from cystic
      tissue removed from ADPKD patients. The monolayers were grown on permeant
      supports, and fluid secretion was initiated by forskolin. The results were
      compared with those obtained with monolayers of Madin-Darby canine kidney (MDCK)
      cells, known to secrete Cl-. In the absence of the agonist, ADPKD monolayers
      absorbed fluid (0.20 +/- 0.02 microliter.cm surface area-2.h-1). Forskolin
      reversed this to secretion (0.60 +/- 0.03 microliter.cm-2.h-1). Control MDCK
      monolayers did not transport fluid in either direction, but forskolin induced
      secretion (0.48 +/- 0.03 microliter.cm-2.h-1). The electrical properties of the
      monolayers were monitored in Ussing chambers. Forskolin increased the
      transepithelial potential difference (Vte) of ADPKD monolayers (-0.9 +/- 0.1 to 
      1.1 +/- 0.1 mV) and the short-circuit current (Isc) (6.6 +/- 0.7 to 9.2 +/- 0.8
      microA/cm2). The transepithelial resistance (Rte) fell (156 +/- 9 to 138 +/- 10
      omega.cm2). Similar results were obtained with MDCK monolayers. The polarity of
      Vte and the direction of the Isc are compatible with the hypothesis that active
      secretion of anion drives fluid secretion. Basolateral application of the Na-K
      2Cl cotransporter, bumetanide, reduced forskolin-stimulated fluid secretion by
      ADPKD monolayers (0.56 +/- 0.05 to 0.28 +/- 0.03), depolarized Vte, and inhibited
      Isc without affecting Rte. Apical application of the Cl- channel blocker,
      diphenylamine-2-carboxylate, also inhibited fluid secretion by ADPKD monolayers
      (0.65 +/- 0.03 to 0.27 +/- 0.02 microliter.cm-2.h-1).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7573489
TI  - Renal expression of osteopontin and alkaline phosphatase correlates with BUN
      levels in aged rats.
AB  - Renal expression of alkaline phosphatase (AP) and osteopontin (OP) in rats of
      different age was examined. Northern blot hybridization showed that AP mRNA was
      reduced moderately, whereas OP mRNA was stimulated drastically in old rats. Dot
      blot quantitation analysis showed that AP mRNA decreased 30% in 24-compared with
      6-mo-old rats. In contrast, OP mRNA increased 3.1- and 9.1-fold, respectively, in
      12- and 24-mo-old rats. beta-Actin mRNA did not change with age. Blood urea
      nitrogen (BUN) increased 47 and 187% in 12- and 24-mo-old rats, respectively.
      Correlation analysis showed that BUN correlated negatively with AP mRNA and
      positively with OP mRNA. No correlation was observed with beta-actin. The
      expression of these markers was also examined in femurs. AP and OP mRNAs were
      marginally reduced in old bones. To test whether the correlation also exists in
      other types of renal insufficiency, we examined these parameters in young rats
      infused with parathyroid hormone (PTH). BUN was elevated 3.5-fold, whereas AP
      mRNA decreased 48%, and OP mRNA increased 15.3-fold in kidneys of PTH-treated
      rats. To elucidate the possible mechanisms that lead to the overexpression of OP
      in kidney, we examined the expression of transforming growth factor-beta 1 (TGF
      beta 1) mRNA. No significant differences in TGF-beta 1 expression were observed
      between young and old rats and control and PTH-treated young rats. Changes in the
      expression of OP were also visualized by immunostaining of renal sections.
      Alterations in the levels of OP and AP were validated by Western blot analysis
      and enzyme assay of homogenate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573488
TI  - Extracellular glucose reduces the responsiveness of mesangial cell ion channels
      to angiotensin II.
AB  - Abnormal cellular ion homeostasis is a well-recognized component of diabetic
      glomerular disease. In cultured rat glomerular mesangial cells, we have
      previously shown that insulin regulates Ca(2+)-dependent activation of 4-pS Cl-
      channels and 27-pS nonselective cation channels (NSCC) by angiotensin II (ANG
      II). To assess whether extracellular glucose also affects mesangial ion channels,
      we applied patch-clamp techniques to cells incubated in constant insulin (100
      mU/ml) and either "normal" (5 mM) or "high" (30 mM) glucose for 1 wk. In normal
      glucose, 100 nM ANG II increased Cl- and NSCC activity by > 16-fold and > 60
      fold, respectivley. Direct release of intracellular Ca2+ ([Ca2+]i) stores (0.25
      microM thapsigargin) mimicked ANG II-induced channel stimulation. In high
      glucose, Cl- and NSCC stimulation by ANG II was attenuated (< 7-fold), whereas
      channel activation by thapsigargin was unaffected. Protein kinase C (PKC)
      inhibition (30-min exposure to 0.5 microM calphostin) or downregulation (24-h
      exposure to 0.1 microM 4 beta-phorbol 12-myristate 13-acetate), but not aldose
      reductase inhibition (0.5 mM sorbinil), restored channel responsiveness to ANG II
      despite high glucose. Channel responsiveness was also restored if mesangial cells
      were coincubated in both high glucose and 500 microM myo-inositol. Acute exposure
      to a synthetic diacylglycerol (100 microM 1-oleoyl-2-acetyl glycerol)
      reestablished channel unresponsiveness to ANG II. We conclude the following in
      rat mesangial cell cultures: 1) Activation of Ca(2+)-dependent Cl- and NSCCs by
      ANG II is reduced by high extracellular glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573490
TI  - Cloning, embryonic expression, and alternative splicing of a murine kidney
      specific Na-K-Cl cotransporter.
AB  - A full-length cDNA encoding the murine renal Na-K-Cl cotransporter (NKCC2) was
      cloned using library screening and anchored polymerase chain reaction. The
      deduced protein sequence contained 1,095 amino acids and was 93.5% identical to
      rabbit NKCC2 and 97.6% identical to rat BSC1. Two potential sites of
      phosphorylation by adenosine 3',5'-cyclic monophosphate-dependent protein kinase
      and seven potential sites of phosphorylation by protein kinase C, which were
      previously identified in the rabbit and rat sequences, were phylogenetically
      conserved in the mouse. The expression of NKCC2 in the mouse was examined with
      Northern blot analysis and in situ hybridization. Expression of NKCC2 was kidney
      specific in both adult and embryonic mice. In the developing metanephros, NKCC2
      was induced at 14.5 days post coitus and was expressed in distal limbs of
      immature loops of Henle but was absent from the ureteric bud, S-shaped bodies,
      and earlier nephrogenic structures. Similar to the rabbit, isoforms of NKCC2 that
      differed in the sequence of a 96-bp segment were identified in the mouse. In situ
      hybridization revealed that the isoforms exhibited different patterns of
      expression in the mature thick ascending limb of the loop of Henle as follows:
      isoform F was most highly expressed in the inner stripe of outer medulla, isoform
      A was most highly expressed in the outer stripe of the outer medulla, and isoform
      B was most highly expressed in the cortical thick ascending limb. To verify that
      the isoforms were generated by alternative splicing of mutually exclusive
      cassette exons, genomic clones encoding murine NKCC2 were characterized. Cassette
      exons were identified that corresponded to each of the three isoforms and were
      flanked by consensus splice donor and acceptor sequences.

PMID- 7573492
TI  - Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats.
AB  - We examined the effect of two endogenous antioxidant agents, taurine and vitamin
      E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered
      diabetic with streptozocin (STZ), were assigned to one of the following groups:
      1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses;
      3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E
      supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The
      survival rate was similar (70-90%) in all groups except vitamin E-treated
      animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was
      elevated in untreated and taurine-treated STZ rats compared with normal or
      insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria
      and albuminuria by nearly 50%. This treatment also prevented glomerular
      hypertrophy, preserved immunohistochemical staining for type IV collagen in
      glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in
      diabetic animals. The changes in renal function and structure in taurine-treated
      diabetic rats were associated with normalization of renal cortical
      malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased
      formation of the advanced glycooxidation products, pentosidine, and fluorescence
      in skin collagen. Administration of the vitamin E-enriched diet exacerbated the
      nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation
      increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and
      accelerated the accumulation of advanced glycosylation end products (AGEs) in
      skin collagen. We conclude that administration of taurine, but not vitamin E, to
      rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of
      taurine is related to reduced renal oxidant injury with decreased lipid
      peroxidation and less accumulation of AGEs within the kidney.

PMID- 7573491
TI  - 1 alpha, 25-dihydroxyvitamin D3 receptor ontogenesis in fetal renal development.
AB  - We used immunohistochemical techniques to examine the distribution of 1 alpha, 25
      dihydroxyvitamin D3 receptors (VDR) in developing rat and mouse kidneys and
      murine metanephric organ culture. In vivo, the patterns of expression in the two
      species were similar despite the slight difference in gestational periods (rat,
      22 days; mouse, 19 days). Starting at gestational day 15, epitopes for VDR were
      found in cells of branching ureteral buds and in surrounding mesenchyme and at
      later developmental stages in glomerular visceral and parietal epithelial cells
      and proximal and distal tubules (DT). Epitopes for the 28-kDa calcium-binding
      protein (calbindin D28k) were found exclusively in DTs starting at gestational
      day 19. The pattern of VDR expression during in vitro nephrogenesis in serum-free
      murine metanephric organ culture paralleled that seen in vivo. At the time of
      explantation into organ culture (gestational day 13), VDR epitopes were not
      detected. By 3 days of in vitro development, VDR expression was identical to that
      found in gestational day 15 metanephroi in vivo. VDR expression after 5 days of
      in vitro development mirrored the pattern of gestational day 17 metanephroi in
      vivo. No calbindin D28k epitopes were seen at any in vitro developmental stage
      studied. We demonstrate for the first time that VDR are present in specific areas
      of the developing rat and mouse kidney early in gestation. Calbindin D28k appears
      later in developing rat and mouse kidney and is distributed differently than the
      VDR. Metanephric organ culture may be a useful model for studying the regulation
      and function of VDR during early renal development.

PMID- 7573493
TI  - Decreased transcription of the sodium-phosphate transporter gene in the
      hypophosphatemic mouse.
AB  - Recently, it has been hypothesized that the proximal tubular Na(+)-Pi transporter
      may play a role in murine X-linked hypophosphatemic vitamin D-resistant rickets.
      In the present investigation, Western blot analysis of renal brush-border
      membrane proteins, utilizing polyclonal antisera raised against the mouse Na(+)
      Pi transporter, revealed a predominant band at 87 kDa in normal and
      hypophosphatemic (Hyp) mice. The intensity of this band was reduced in the Hyp
      mouse by 4.5-fold (Hyp/normal = 0.22 +/- 0.04, n = 3, P < 0.05). Additionally,
      immunohistochemical analysis of kidney cortex in both mice localized the protein
      to the apical membrane of the proximal tubules. Relative transcription rates of
      the Na(+)-Pi transporter gene in the normal and Hyp mouse were then investigated.
      Nuclear run-on assays showed a 51 +/- 0.02% decreased rate of transcription of
      the Na(+)-Pi transporter gene in the Hyp mice (n = 3). Thus abnormal
      transcriptional control of this gene in the Hyp mouse likely plays a role in X
      linked hypophosphatemia.

PMID- 7573494
TI  - Endothelin receptor mRNA expression in renal medulla identified by in situ RT
      PCR.
AB  - Three subtypes of endothelin (ET) receptors have been identified by cDNA cloning,
      namely ET-RA, ET-RB, and ET-RC. In the current study the precise cellular
      distribution of the ET receptor subtypes in the renal medulla was explored by
      detecting the corresponding polymerase chain reaction (PCR)-amplified cDNAs by in
      situ reverse transcription (RT)-PCR. The PCR-amplified cDNAs were detected either
      by direct incorporation using digoxigenin-dUTP (dig-dUTP) as a nucleotide
      substrate in the PCR reaction or by in situ hybridization with the dig-dUTP
      labeled probe. ET-RB mRNA was detected exclusively in the epithelial cells of the
      inner and outer medullary collecting duct. In contrast, ET-RA message was
      observed primarily in interstitial cells and pericytes of the vasae rectae in the
      outer and inner medulla. Southern blot analysis of PCR-amplified cDNAs reverse
      transcribed from extracted RNA of rat renal medulla confirmed the specificity of
      the RT-PCR products. ET-RC mRNA was not detected. We conclude that ET-RB is the
      major ET receptor found in rat renal medulla and is expressed exclusively on
      inner medullary collecting duct cells. The pattern of ET receptor mRNA expression
      described suggests different physiological actions for ET on the diverse cellular
      structures of the renal medulla.

PMID- 7573496
TI  - Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced
      vasospasm: role of ET-1.
AB  - The purpose of this study was to test whether endothelium-dependent relaxation is
      decreased during acute vasospasm following subarachnoid hemorrhage (SAH) and the
      mechanism underlying the decrease. Basilar artery in situ was 35% constricted 3
      days following injection of autologous arterial blood into the rabbit cisterna
      magna compared with vessels from control rabbits. In situ suffusion with the
      endothelium-dependent relaxant, acetylcholine (ACh; 10 microM), relaxed resting
      and serotonin (5-HT)-contracted control vessels but not vasospastic and 5-HT
      contracted vasospastic vessels. In contrast, the relaxant potency and efficacy of
      ACh was similar in control and vasospastic vessels contracted with 5-HT in vitro.
      In situ suffusion with the ETA-receptor antagonist, BQ-123 (1 microM), reversed
      the vasospasm by 51% and restored the magnitude of ACh relaxation of vasospastic
      and 5-HT-contracted vasospastic vessels to that of controls. ACh in situ and in
      vitro relaxed endothelin-1 (ET-1)-contracted control vessels to a smaller
      magnitude than 5-HT-contracted control vessels. These results suggest, in
      contrast to previous studies, that endothelium-dependent relaxation is decreased
      during acute vasospasm following SAH. The decreased endothelium-dependent
      relaxation is secondary to the underlying ET-1-mediated spasm. The inhibition of
      endothelium-dependent relaxation observed in situ following SAH cannot be
      demonstrated in vitro, presumably due to loss of the ET-1-mediated vasospasm.

PMID- 7573495
TI  - Age-associated increase in rat ventricular ANP gene expression correlates with
      cardiac hypertrophy.
AB  - Atrial natriuretic peptide (ANP), a cardiac-specific hormone, is stored in the
      atria and released in response to atrial stretch. During cardiac hypertrophy, ANP
      gene expression is markedly upregulated in the left ventricle (LV). Because the
      hearts of normotensive senescent rats exhibit left atrial (LA) and left
      ventricular (LV) hypertrophy and dilatation, we examined ANP mRNA levels by
      Northern blot analysis and ANP peptide concentrations by radioimmunoassay in
      atria, LVs, and plasma of rats at 2, 6, 18, and 22-24 mo of age. Compared with
      LVs of 6-mo-old rats, the LV-to-body weight ratio was elevated 30% by 18 mo of
      age, whereas levels of ANP mRNA were elevated twofold (not significant) and
      sevenfold (P < 0.05) in the LV of 18- and 22- to 24-mo-old rats, respectively.
      The concentration of immunoreactive ANP (ir-ANP) exhibited a four- to fivefold
      increase in LVs of 18- and 22- to 24-mo-old rats compared with values for 6-mo
      old rats (43 +/- 4 pmol/g wet wt; means +/- SE). Among 18-and 22- to 24-mo-old
      rats a significant correlation was observed between ANP peptide concentration and
      LV hypertrophy (r 2 = 0.64). Levels of ANP mRNA and ir-ANP in the atria exhibited
      only modest changes with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573497
TI  - Effects of inhibiting neutral endopeptidase and kininase II on coronary and
      systemic hemodynamics in rats.
AB  - To determine whether neutral endopeptidase (NEP) and kininase II (angiotensin
      converting enzyme, ACE) influence coronary hemodynamics, we compared the effects
      of inhibiting NEP, ACE, or both before and after isoproterenol (50 mg/kg ip). We
      measured flow and resistance using radioactive microspheres in 90 anesthetized
      rats which received the NEP inhibitor phosphoramidon (2.5 mg/kg), the ACE
      inhibitor captopril (2.5 mg/kg), both combined, or vehicle alone. Before
      isoproterenol, inhibiting NEP, ACE, or both increased left ventricular blood flow
      by 48 +/- 10 (SE), 33 +/- 9, and 10 +/- 6%, respectively, and decreased left
      ventricular vascular resistance by 26 +/- 6, 31 +/- 10, and 10 +/- 6%,
      respectively. After isoproterenol, NEP inhibition augmented the decrease in left
      ventricular vascular resistance (25 +/- 6% decrease within 90 s of isoproterenol
      vs. 8 +/- 5% in controls). ACE inhibition did not augment the decrease in
      resistance but inhibiting both enzymes did so to a lesser extent than inhibiting
      NEP. These effects cannot be explained by vascular responses secondary to changes
      of myocardial oxygen consumption. We conclude that NEP and ACE are regulators of
      myocardial blood flow.

PMID- 7573499
TI  - Polystyrene microspheres decrease bronchial artery resistance in anesthetized
      sheep.
AB  - The use of microspheres to measure tissue blood flow requires that the
      microspheres themselves do not alter regional arterial tone. To determine whether
      microspheres affected bronchial artery resistance, we cannulated and perfused the
      bronchial artery in anesthetized sheep. In seven sheep, the change in bronchial
      artery pressure at constant flow was recorded during infusion of 5 doses (1 x
      10(5), 2 x 10(5), 5 x 10(5), 1 x 10(6), and 1.5 x 10(6)) of 15-microns
      microspheres. Microspheres produced a dose-dependent, self-limited decrease in
      bronchial artery pressure (1.5 x 10(6) microspheres decreased bronchial artery
      pressure by 36% for 31 min). This was a decrease in bronchial artery resistance,
      as evidenced by a shift in the slope, but not the intercept, of a pressure-flow
      curve (n = 4 sheep). Left atrial injection of 1 x 10(7) microspheres decreased
      bronchial artery resistance by 17% in six sheep with intact bronchial arteries in
      which flow was measured by ultrasound probe. The adenosine-receptor antagonist 8
      phenyltheophylline attenuated the fall in resistance by 79% (n = 4 sheep).
      Cyclooxygenase inhibition by indomethacin attenuated the response by 37% (n = 4
      sheep). These results suggest that microspheres caused the release of adenosine
      and a vasodilator prostaglandin. Repetitive measurements of bronchial blood flow
      by microspheres could overestimate true bronchial blood flow if the interval
      between measurements is < 30 min.

PMID- 7573500
TI  - Effect of central infusion of benzamil on Dahl S rat hypertension.
AB  - The effect of continuous central infusion of benzamil, a Na+ channel-selective
      amiloride analogue, on the salt-induced hypertension in inbred Dahl salt
      sensitive (SS/jr) rats was assessed. The continuous intracerebroventricular or
      subcutaneous infusion of benzamil at doses which have no effect when infused
      systemically was started at the same time or 2 wk after saline was substituted
      for drinking water, when the rats' blood pressures had become significantly
      elevated. Within 13 days, drinking saline caused a similar and significant
      increase in the blood pressures of rats receiving the vehicle
      intracerebroventricularly and 1 microgram/h of benzamil subcutaneously, which
      persisted throughout the 4-wk experiment. The intracerebroventricular infusion of
      1 or 0.3 microgram/h benzamil, started at the same time the salt challenge was
      instituted, significantly deterred the increase in blood pressure over 4 wk. The
      intracerebroventricular, but not the subcutaneous, infusion of benzamil at 0.5
      microgram/h arrested the increase in blood pressure in rats that were already
      hypertensive after 12 days on saline. Within 3 days the pressures in the
      intracerebroventricular and subcutaneous benzamil groups became significantly
      different, due to the further increase of the blood pressure in those animals
      receiving the intracerebroventricular vehicle with subcutaneous benzamil. There
      was no significant difference in weight gain throughout the experiment or in 24-h
      urine volumes and urinary Na(+)-to-K+ ratio at days 5 and 12 of benzamil infusion
      between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573501
TI  - Capillary diameter changes during low perfusion pressure and reactive hyperemia
      in rabbit skeletal muscle.
AB  - Capillary diameter changes were studied in the tenuissimus muscle of 29 urethan
      anesthetized New Zealand White rabbits. Capillaries were visualized with
      transillumination bright-field microscopy (saltwater lens, x 50; resolution
      approximately 0.3 microns). Median capillary diameter during the control period
      was 4.4 microns (range 3.2-6.9 microns). Complete aortic occlusion resulted in a
      reduction of median femoral arterial pressure to 17 mmHg (range 4-22 mmHg).
      During 2 min of occlusion, capillary diameter decreased by 6%, with greater
      change on the arteriolar side of the capillary than on the venular side. During
      reactive hyperemia after release of the occluder, capillary diameter maximally
      increased by 12% compared with the control period, with a larger response at the
      arteriolar end of the capillary than at the venular end. Median capillary
      resistance was estimated to increase by 27% during occlusion and to decrease by
      36% during peak reactive hyperemia. The observed diameter changes are compatible
      with the idea that capillaries change their diameter relative to changes in
      transmural pressure.

PMID- 7573498
TI  - Inhibition of the creatine kinase reaction decreases the contractile reserve of
      isolated rat hearts.
AB  - To define the relation between phosphoryl transfer via creatine kinase (CK) and
      the ability of the intact beating heart to do work, we chemically inhibited CK
      activity and then measured cardiac performance under physiological and acute
      stress conditions. Isolated perfused rat hearts were exposed to iodoacetamide
      (IA) and subjected to one of three cardiac stresses: hypercalcemic (Ca2+ = 3 mM)
      buffer perfusion (n = 7), norepinephrine (2 mumol/min) infusion (n = 6), or
      hypoxic buffer perfusion (n = 5). IA decreased CK activity to near zero, measured
      in intact hearts by 31P magnetization transfer, and to 2% of control CK activity,
      measured in myocardial homogenates. The CK isoenzyme profile was unchanged,
      suggesting nonselective IA inhibition of all isoenzymes. Mitochondria isolated
      from IA-treated hearts had normal ADP:O ratios, state 3 respiratory rates, and
      unchanged acceptor and respiratory control ratios. Neither actomyosin
      adenosinetriphosphatase nor adenylate kinase activities were changed. After IA
      exposure, end-diastolic pressure, left ventricular developed pressure, and heart
      rate were unchanged for at least 30 min at physiological perfusion pressures, but
      large changes were observed during stress conditions. The increase in left
      ventricular developed pressure induced by hypercalcemic perfusion and by
      norepinephrine infusion decreased by 39 and 54%, respectively. During hypoxia,
      the rate of phosphocreatine depletion was decreased by 57%, left ventricular
      developed pressure declined, and end-diastolic pressure increased faster than in
      controls. These results show that inhibition of CK to < 2% of control activity by
      IA reduced contractile reserve by approximately 50%. We conclude that CK activity
      is essential for the expression of the full dynamic range of myocardial
      performance.

PMID- 7573504
TI  - Dynamic changes in G alpha i-2 levels in rat hearts associated with impaired
      heart function after myocardial infarction.
AB  - The objective of this study was to determine if levels and function of Gs alpha
      and G alpha i-2 in rat hearts change over time following acute myocardial
      infarction (MI), and if so, whether the changes in G proteins are associated with
      changes in heart function. As compared with sham-operated controls, the G alpha i
      2 level of MI rats did not change at day 1, increased by 64% at day 3 (P < 0.01)
      and by 55% at day 9 (P < 0.05) accompanied by reduced adenylyl cyclase activity,
      and returned to control by day 21. By contrast, the Gs alpha level did not change
      at any time. Cardiac function in MI animals was markedly impaired at days 1, 3,
      and 9 as evidenced by substantial elevation in LVEDP and reduction in maximum
      rates of pressure development and relaxation, and was partially restored at day
      21. Increased G alpha i-2 level in MI rats correlated significantly to severity
      of impaired cardiac function. The results show a three-phase dynamic pattern in G
      alpha i-2 level following acute MI: a lag phase, an increased expression phase
      associated with marked impairment of heart function, and a late phase in which
      the expression returns to control level accompanied by partially restored cardiac
      function.

PMID- 7573503
TI  - Nitric oxide does not mediate autoregulation of retinal blood flow in newborn
      pig.
AB  - Isoflurane-anesthetized newborn pigs were used to test the hypothesis that nitric
      oxide mediates autoregulatory dilations of retinal arterioles. Fundus images were
      monitored by videomicroscopy at x310, and stimulus-induced changes in retinal
      arteriolar diameter were measured by on-line image analysis. Dilatative responses
      to systemic hypoxia (arterial O2 tension 20-30 mmHg), hypotension (mean arterial
      blood pressure 40 mmHg), or hypercapnia (arterial CO2 tension 70-85 mmHg) were
      assessed after intravitreal microsuffusion of the nitric oxide synthase inhibitor
      NG-monomethyl-L-arginine (L-NMMA) over the observed arterioles. Twenty-five
      nanomoles L-NMMA constricted arterioles by 24 +/- 2% (P < 0.01; n = 17 pigs); a
      significant constriction (14 +/- 2%) was still observed 80 min after drug
      administration (n = 5). Complete nitric oxide synthase inhibition at this dose
      was indicated by the findings that co-administration of 2.5 mumol L-arginine
      reversed this constriction within 17 +/- 2 min (n = 3), that L-NMMA, but not D
      NMMA, completely inhibited the 20 +/- 3% P < 0.01) arteriolar dilation induced by
      intravitreal acetylcholine (7.5 nmol; n = 4), and that no additional constriction
      was evidenced after administration of a 10-fold greater concentration of L-NMMA
      (n = 8). However, despite the prominent arteriolar constriction induced by L-NMMA
      under baseline conditions, increases in retinal arteriolar diameter still
      occurred in response to hypoxia (n = 5), hypotension (n = 4), or hypercapnia (n =
      5) in animals pretreated with 50 nmol L-NMMA; these responses did not differ
      significantly from arteriolar dilations observed in untreated control animals (n
      = 16) subjected to the same stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573502
TI  - Cardiac energetics, cell volumes, sodium fluxes, and membrane permeability: NMR
      studies of cold ischemia.
AB  - Intracellular sodium accumulation, cellular swelling, and energy deficiency are
      ischemia-associated processes that participate in the transition to irreversible
      ischemic injury. This study aims to determine the relationship among these
      parameters in intact rat hearts during global ischemia at 4 degrees C. High
      energy phosphates were determined by 31P nuclear magnetic resonance,
      intracellular sodium accumulation was measured by 23Na spectroscopy with the
      shift reagent dysprosium triethyl tetraaminohexaacetic acid [Dy(TTHA)3(-)], and
      cell volumes were measured by 59Co and 1H spectroscopy with use of the
      extracellular marker Co(CN)3-(6). Intracellular sodium flux rates were 1.53 +/-
      0.17, 0.17 +/- 0.05, and 0.30 +/- 0.06 mumol.g dry wt-1.min-1 at 0-1.5, 2-7, and
      9-12 h, respectively. Sodium influx resulted in accumulation of the ion: 10%
      after 4 h, 16% after 10 h, and 29% after 12 h. Water followed sodium into the
      cells at two constant molar ratios (Na+/H2O): 3.80 +/- 0.15 x 10(-3) during the
      first 8 h of ischemia and 7.8 x 10(-3) at 8-12 h. Relative to initial
      intracellular volume, cells swelled by 38% after 8 h and 46% after 12 h;
      reperfusion reduced cellular swelling to 25 and 36%, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573505
TI  - Antagonism of vasopressin V1 receptors in NTS attenuates baroreflex control of
      renal nerve activity.
AB  - Previous work has shown that arginine vasopressin (AVP) present in the nucleus
      tractus solitarius (NTS) contributes to the control of peripheral cardiovascular
      parameters such as arterial pressure, heart rate, and sympathetic activity. In
      this study, we attempted to elucidate the influence of AVP in the NTS on
      baroreflex control of mean arterial pressure (MAP) and renal sympathetic nerve
      activity (RSNA) in urethan-anesthetized rats. To test the baroreflex, the aortic
      depressor nerve (ADN) was stimulated over a range of frequencies (1-15 Hz) to
      produce frequency-response curves for MAP and RSNA. The vasopressin V1-receptor
      antagonist [d(CH2)5Tyr(Me)]AVP (aAVP) was microinjected bilaterally or
      unilaterally into the caudal NTS to eliminate the influence of endogenous AVP on
      decreases in MAP and RSNA elicited by ADN stimulation. Bilateral microinjection
      of 10 or 100 ng aAVP significantly attenuated the decreases in RSNA elicited by
      ADN stimulation. Decreases in MAP were only attenuated following bilateral
      microinjection of 100 ng aAVP. Unilateral microinjection of the same doses of
      aAVP did not influence baroreflex control of MAP or RSNA. These results indicate
      that endogenous AVP within the NTS contributes to cardiovascular regulation. They
      also suggest that AVP within the NTS may specifically influence baroreflex
      control of RSNA.

PMID- 7573506
TI  - Expression of protein kinase C isoforms during cardiac ventricular development.
AB  - The expression of protein kinase C (PKC) isoforms (PKC-alpha, PKC-beta 1, PKC
      delta, PKC-epsilon, and PKC-zeta) was studied by immunoblotting in whole
      ventricles of rat hearts during postnatal development (1-26 days) and in the
      adult. PKC-alpha, PKC-beta 1, PKC-delta, PKC-epsilon, and PKC-zeta were detected
      in ventricles of 1-day-old rats, although PKC-alpha and PKC-beta 1 were only
      barely detectable. All isoforms were rapidly downregulated during development,
      with abundances relative to total protein declining in the adult to < 25% of 1
      day-old values. PKC-beta 1 was not detectable in adult ventricles. The specific
      activity of PKC was also downregulated. The rat ventricular myocyte becomes
      amitotic soon after birth but continues to grow, increasing its protein content
      40- to 50-fold between the neonate and the 300-g adult. An important question is
      thus whether the amount of PKC per myocyte is downregulated. With the use of
      isolated cells, immunoblotting showed that the contents per myocyte of PKC-alpha
      and PKC-epsilon increased approximately 10-fold between the neonatal and adult
      stages. In rat ventricles, the rank of association with the particulate fraction
      was PKC-delta > PKC-epsilon > PKC-zeta. Association of these isoforms with the
      particulate fraction was less in the adult than in the neonate. In primary
      cultures of ventricular myocytes prepared from neonatal rat hearts, 1 microM 12-O
      tetradecanoylphorbol-13-acetate (TPA) elicited translocation of PKC-alpha, PKC
      delta, and PKC-epsilon from the soluble to the particulate fraction in < 1 min,
      after which time no further translocation was observed. Prolonged exposure (16 h)
      of myocytes to 1 microM TPA caused essentially complete downregulation of these
      isoforms, although downregulation of PKC-epsilon was slower than for PKC-delta.
      In contrast, PKC-zeta was neither translocated nor downregulated by 1 microM TPA.
      Immunoblotting of human ventricular samples also revealed downregulation of PKC
      relative to total protein during fetal/postnatal development.

PMID- 7573507
TI  - Endotoxin-induced left ventricular depression is blocked by nitrogen mustard or
      dimethylthiourea in rabbits.
AB  - We examined endotoxin-induced myocardial depression in 31 anesthetized rabbits
      using left ventricular end-systolic and end-diastolic pressure-volume
      relationships (sonomicrometers). In the control group, endotoxin (100
      micrograms/kg iv) induced systolic depression (> 10% increase in end-systolic
      volume at matched end-systolic pressure) in 9 of 16 and diastolic dilation (> 10%
      increase in end-diastolic volume at matched end-diastolic pressure) in 8 of 16
      rabbits within 7 h, unrelated to hypotension, acidosis, or hypoxia. Seven rabbits
      were pretreated with nitrogen mustard (1-2 mg/kg iv 4 and 2 days before) to
      decrease circulating neutrophils and monocytes by 98%. Endotoxin did not induce
      systolic depression in any rabbit (P = 0.01 compared with control), and diastolic
      dilation developed in one rabbit (P = 0.12). In eight rabbits pretreated with
      dimethylthiourea (DMTU; 500 mg/kg iv 30 min before), an intracellular free
      radical scavenger, systolic depression developed in one (P = 0.05) and diastolic
      dilation in five (P = 0.44). We conclude that cells inhibited by nitrogen mustard
      (e.g., neutrophils, monocytes, or macrophages) mediate endotoxin-induced left
      ventricular systolic depression. DMTU inhibited endotoxin-induced systolic but
      not diastolic dysfunction.

PMID- 7573508
TI  - NOS expression is increased in endothelial cells exposed to plasma from women
      with preeclampsia.
AB  - Endothelial cell function is proposed to be altered by a factor(s) in the
      maternal circulation of women with the pregnancy disorder preeclampsia. Our
      initial hypothesis was that in preeclampsia, such factor(s) would reduce
      synthesis of nitric oxide (NO) by endothelial cells. However, we previously
      observed increased NO synthase activity in endothelial cells exposed to plasma
      from preeclamptic women. This study tested whether exposing cells to plasma from
      preeclamptic women increased transcription and/or translation of endothelial NO
      synthase. Cultured bovine coronary microvascular endothelial cells were exposed
      to 2% plasma from patients with preeclampsia and patients with uncomplicated
      pregnancies. Nitrite production was greater in endothelial cells exposed to
      plasma from preeclamptic women (8.97 +/- 0.54 vs. 6.39 +/- 0.59 nmol
      nitrites.10(6) cells-1 x 24 h-1; P < 0.05). Similarly, endothelial NO synthase
      mass as measured by Western immunoblotting was significantly increased (20,980 +/
      1,406 vs. 15,047 +/- 1,003 absorbancy units; P < 0.02). There was no detectable
      difference in mRNA for endothelial NO synthase. However, actinomycin (3
      micrograms/ml), a transcription inhibitor, significantly decreased nitrite
      production only in cells exposed to plasma from preeclamptic women (5.28 +/- 0.52
      vs. 3.56 +/- 0.36 nmol.10(6) cells-1 x 24 h-1, P < 0.05). These findings indicate
      a regulation of the "constitutive" isoform of NO synthase by factor(s) in the
      blood of preeclamptic women, which may have significance in this pathological
      condition of pregnancy.

PMID- 7573509
TI  - Intracoronary nitric oxide improves postischemic coronary blood flow and
      myocardial contractile function.
AB  - In the present study a novel nitric oxide (NO) donor, CAS-1609, was utilized as a
      means of coronary NO replenishment in a canine model of myocardial ischemia
      reperfusion. Administration of CAS-1609 (1.25 mg iv) 10 min before reperfusion,
      followed by a 1 mg/h intracoronary infusion throughout the 4.5-h reperfusion
      period, resulted in significant improvement in postischemic transmural myocardial
      blood flow (0.66 +/- 0.09 vs. 0.37 +/- 0.08 ml.min-1.g-1 for saline vehicle, P <
      0.05). Dogs receiving NO supplementation also exhibited a significant recovery of
      myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection
      fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Moreover, myocardial
      necrosis as a percentage of the area at risk was reduced from 28.9 +/- 4.3% in
      the saline group to 8.5 +/- 2.6% in the CAS-1609 group (P < 0.01), while ischemic
      zone myeloperoxidase activity, indicative of neutrophil infiltration, was also
      attenuated by 70% with NO therapy. Injection of acetylcholine and nitroglycerin
      into the left circumflex coronary artery revealed a significant impairment of
      vasodilator responses in the saline vehicle dogs at 2 h of reperfusion. However,
      dogs treated with the NO donor demonstrated postischemic vasodilator responses
      which were similar to baseline (P = not significant vs. baseline). These studies
      demonstrate that intracoronary administration of NO significantly augments
      postischemic coronary blood flow and contractile function following ischemia and
      reperfusion. In addition, NO therapy reduces coronary vascular injury, attenuates
      myocardial necrosis, and reduces neutrophil infiltration. The cardioprotective
      actions of intracoronary NO administration may be related to the potent
      antineutrophil actions of NO.

PMID- 7573510
TI  - Mechanisms of vascular preservation by a novel NO donor following rat carotid
      artery intimal injury.
AB  - We studied the effects of a novel organic nitric oxide (NO) donor, 4
      hydroxymethyl-furazan-3-carboxylic acid-2-oxide (CAS-1609), in a rat carotid
      artery intimal injury model. The NO donor, CAS-1609, or its non-NO-donating
      control compound, 4-hydroxymethyl-furazan-3-carboxylic acid (C-93-4845), was
      infused intravenously at 30 micrograms/day. Seven days after injury, carotid
      artery rings contracted only 56 +/- 6 mg to NG-nitro-L-arginine methyl ester in C
      93-4845-treated rats, compared with 120 +/- 17 mg in CAS-1609-treated rats (P <
      0.02), indicating a preservation of endogenous NO release. Improved responses to
      the endothelium-dependent dilator, acetylcholine, also occurred in injured
      arteries treated with CAS-1609. Morphometric analysis of injured carotid arteries
      given the inactive compound showed marked intimal thickening with an intimal-to
      medial ratio (I/M) of 0.76 +/- 0.02, compared with a significantly lower I/M of
      0.32 +/- 0.04 (P < 0.01) in injured carotid arteries given CAS-1609.
      Additionally, CAS-1609 was found to have a concentration-dependent stimulatory
      effect on cultured rat aortic endothelial cell proliferation (P < 0.01) but and
      inhibitory effect on platelet-derived growth factor-BB (10 ng/ml)-stimulated rat
      aortic smooth muscle cell proliferation (P < 0.01). This is the first study to
      demonstrate that NO plays a dual role in vascular cell proliferation, stimulating
      endothelial cells but inhibiting smooth muscle cell proliferation. This dual
      effect of NO on cell proliferation is associated with an in vivo reduction in
      neointimal thickening and an acceleration of endothelial recovery determined by
      both anatomic and functional methods.

PMID- 7573511
TI  - Regional wall motion and strain analysis across stages of Fontan reconstruction
      by magnetic resonance tagging.
AB  - To determine whether systolic regional wall deformation and motion, which may be
      used as an index of mechanical function, change with surgical intervention in
      patients with a functional single ventricle, a noninvasive magnetic resonance
      tagging technique was used to examine 33 such patients at all stages of Fontan
      reconstruction. The systolic motion of the intersection points was tracked to
      determine regional twist and radial shortening. Finite strain analysis was
      applied to the grid lines, and principal E1 strains were derived. The results
      were as follows. 1) Fontan and prebidirectional cavopulmonary anastomosis
      (hemiFontan) groups had the highest compressive strains, and regional
      heterogeneity of strain was least in the Fontan group. 2) Fontan patients had
      endocardial/epicardial strain different from the other surgical subgroups as well
      as the normal left ventricle, while the pre- and post-hemiFontan groups had
      basal/apical short-axis strain different from Fontan patients and normal
      subjects. 3) Functional single left ventricles had a different strain
      distribution across wall regions and surgical subgroup from functional single
      right ventricles. 4) Contrary to the normal human adult studied by the same
      method, which twists uniformly counterclockwise, 31 of 33 single ventricles,
      regardless of ventricular morphology or surgical subgroup, twisted
      counterclockwise in one region, clockwise in another, and met at a "transition
      zone" of no twist, which had the highest strains of all regions. 5) Radial
      contraction was greatest in the superior walls and least at the inferior walls of
      single-ventricle patients regardless of morphology. In the Fontan group, the
      inferior walls moved paradoxically. In conclusion, markedly different strain
      characteristics are noted at each stage of Fontan reconstruction, across various
      wall regions, and between ventricular morphological groups. Differences in
      regional wall motion were demonstrated in functional single ventricles throughout
      Fontan reconstruction regardless of morphology, and differences in associated
      strains and radial contraction were noted across various wall regions and
      surgical subgroups. These may play an important role in the energetics of the
      heart and the long-term viability of the single ventricle.

PMID- 7573512
TI  - Overdrive suppression of spontaneously beating chick heart cell aggregates:
      experiment and theory.
AB  - In spontaneously beating chick heart cell aggregates, sustained periodic
      stimulation at a rate faster than the intrinsic frequency is generally followed
      by a transient slowing of the automatic rhythm called "overdrive suppression." We
      characterize the qualitative aspects of overdrive suppression using three sets of
      experimental protocols: 1) stimulation at a fixed frequency with various numbers
      of stimuli, 2) stimulation at different frequencies, 3) stimulation with
      different intensities. We develop a mathematical model based on a system of
      nonlinear ordinary differential equations to account for the experimental
      observations. The main idea of the model is that overdrive suppression arises as
      a result of a hyperpolarizing current that is induced by action potentials. This
      work shows that the frequency of action potentials is the major determinant of
      overdrive suppression. Consequently, during periodic pacing of spontaneous
      oscillators at different rates, the fastest frequency where 1:1 entrainment can
      be maintained is associated with maximal overdrive suppression. This type of
      model is complementary to the development of a rigorous ionic model and can help
      provide insight into the physiological mechanisms of overdrive suppression.

PMID- 7573513
TI  - Spatiotemporal changes of Ca2+ during electrically evoked contractions in atrial
      and ventricular cells.
AB  - Spatial and temporal changes of intracellular calcium ion concentration ([Ca2+]i)
      during stimulated contractions were observed by confocal microscopy in rat
      ventricular and guinea pig atrial myocytes. Fluorescence intensity profiles in
      fluo 3-acetoxymethyl ester (fluo 3-AM)-loaded cells were collected from the
      entire cell, selected regions of the cell, or along a single scanned line across
      the cell. In rat ventricular myocytes, the increase of [Ca2+]i after a single
      stimulus from field electrodes occurred synchronously across the cell whether
      fluo 3 fluorescence was monitored in a narrow region aligned with the long axis
      of the cell or in line-scan images of a single z-line across the cell. However,
      during the onset of Ca2+ channel blockade by nifedipine (5 microM), electrical
      stimulation produced spatially nonuniform, focal increases of [Ca2+]i. In guinea
      pig atrial myocytes, stimulated increases of [Ca2+]i first appeared in focal
      regions at the cell periphery before spreading to the cell interior. Line-scan
      images showed the peripheral rise of [Ca2+]i led that at the center of the cell
      by 34 +/- 4 ms (mean +/- SE, n = 3). These data demonstrate that the t-tubular
      network ensures synchronous increases of [Ca2+]i throughout the cell during an
      action potential. In the absence of t tubules or when the number of sarcolemmal
      Ca2+ channels opened by membrane depolarization is greatly reduced, stimulated
      increases of [Ca2+]i can be observed to arise in focal regions of the cell.

PMID- 7573514
TI  - Permissive role of NO in alpha 2-adrenoceptor-mediated dilations in rat cerebral
      arteries.
AB  - Dilations produced with UK-14304, a selective alpha 2-adrenoceptor agonist, in
      rat middle cerebral arteries (MCAs) were blocked after removal of the endothelium
      or inhibition of nitric oxide synthase (NOS). After endothelium removal or
      inhibition of NOS, the addition of subthreshold doses of an exogenous nitric
      oxide (NO) donor, S-nitroso-N-acetylpenicillamine, restored the dilations
      produced by UK-14304. In a similar manner the guanosine 3',5'-cyclic
      monophosphate (cGMP) analogues 8-bromoguanosine 3',5'-cyclic monophosphate and
      N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate restored the dilations of
      MCAs after endothelial removal. Because NO cannot be synthesized and released in
      MCAs after inhibition of NOS, it cannot be directly responsible for the dilation.
      The basal release of NO from the endothelium acts permissively in the
      vasodilation by maintaining adequate levels of cGMP. Removal of this basal
      release of NO by removal of endothelium or inhibition of NOS abolishes the alpha
      2-adrenoceptor-mediated dilation.

PMID- 7573515
TI  - Cardiac muscle diseases in genetically engineered mice: evolution of molecular
      physiology.
AB  - Recent advances in molecular, cellular, and genetically based technologies now
      offer the possibility of generating genetically engineered mice that display
      physiological phenotypes with direct relevance to human pathophysiological
      states. The ability to create gene ablations, gene duplications, and gene
      modifications should allow the use of genetic approaches to map in vivo pathways
      responsible for complex physiological phenotypes. Recent work from our laboratory
      utilizing this approach to study cardiac muscle diseases in both the adult
      context (cardiac hypertrophy) and in the embryonic context (congenital
      ventricular defects) will be discussed, as well as the steps that led to the
      generation and characterization of these novel mouse model systems. A large body
      of work from independent laboratories now points to the inception of a new field
      of molecular physiology that will fuse mouse genetics and in vivo physiology
      using appropriate miniaturized physiological technology. Recent advances and
      prospects for future directions are summarized.

PMID- 7573516
TI  - A human calcium-activated potassium channel gene expressed in vascular smooth
      muscle.
AB  - Large-conductance Ca(2+)-activated K+ (BK) channels are widespread and
      functionally heterogeneous. In other classes of K+ channels, functional
      heterogeneity derives from large gene families, alternative splicing,
      heterologous subunit composition, and functional modulation. The molecular basis
      of mammalian BK channel heterogeneity is unknown, since only a single gene (mSlo)
      has been identified. BK channels in native vascular smooth muscle have an
      apparent Ca2+ sensitivity approximately 10-fold greater than native brain or
      skeletal muscle channels, or cloned mSlo channels. Using mSlo as a low-stringency
      probe, we screened human arterial smooth muscle and genomic libraries extensively
      in search of genes or splice variants with novel properties. We isolated the
      human homologue of mSlo, including two novel splice variant forms, but found no
      other related genes. Electrophysiological characterization of the hSlo clones in
      Xenopus oocytes and Chinese hamster ovary cells gave BK currents that were not
      measurably different from mSlo currents. However, coexpression of hSlo with a
      recently cloned beta-subunit derived from smooth muscle dramatically increased
      apparent Ca2+ sensitivity. Thus alpha-subunits alone may not determine Ca2+
      sensitivity of vascular smooth muscle BK channels. hSlo was mapped to human
      chromosome 10q23.1, and the genomic structure was analyzed. Immediately after the
      amino terminal, two unusual regions of trinucleotide repeating sequences are
      present. The first of these regions encodes polyglycine, and the second encodes
      polyserine. Both regions of repeated sequence are conserved between the mouse and
      human genome.

PMID- 7573517
TI  - Characterization of Ca(2+)-release channels in fetal and adult rat hearts.
AB  - The goal of this study was to characterize the Ca(2+)-release channel in whole
      homogenates of left (LV) and right ventricles (RV) of fetal (22 days in
      gestation) and adult Sprague-Dawley rat hearts using [3H]ryanodine binding and
      45Ca2+ fluxes. Although many features of the Ca(2+)-release channels were similar
      in fetal and adult hearts, biochemical assays revealed quantitative differences.
      Similar properties include 1) Ca(2+)-sensitive cooperative ryanodine binding to
      Ca(2+)-release channel, measured as Ca2+ concentration for half-maximal
      activation (fetal LV: 0.13 +/- 0.02 microM; adults LV: 0.15 +/- 0.02 microM) and
      Hill coefficient (fetal LV: 2.5 +/- 0.9; adult LV: 2.7 +/- 0.5), and 2) caffeine
      sensitive ryanodine binding, measured as the percent increase in ryanodine
      binding induced by caffeine (fetal LV: 148.8 +/- 16.9% vs. adult LV: 171.4 +/-
      34.9%). The distinguishing property was the lower Ca(2+)-release channel density
      in the fetal heart (LV: 0.22 +/- 0.03 pmol/mg protein) compared with adult heart
      (LV: 0.59 +/- 0.04 pmol/mg protein; P < 0.05), as determined by [3H]ryanodine
      binding. The lower density of Ca(2+)-release channel is supported by the finding
      that there is very low ryanodine-sensitive oxalate-supported 45Ca2+ uptake in the
      fetal heart. The tested characteristics of the Ca(2+)-release channel were
      similar between LV and RV in both fetal and adult rat hearts. Ou results indicate
      that expression of Ca2+-release channels in sarcoplasmic reticulum increases
      during postnatal growth in the rat heart. This is consistent with previous
      physiological reports that Ca2+ available for excitation-contraction coupling in
      the fetal heart is derived mainly from transsarcolemmal Ca2+ influx.

PMID- 7573519
TI  - An ATP-activated nonselective cation channel in guinea pig ventricular myocytes.
AB  - Extracellular ATP released from nerves onto vascular smooth muscle or released
      from damaged tissues during traumatic injury, shock, or ischemia profoundly
      alters cardiovascular physiology. We have used patch-clamp methods to investigate
      the effects of extracellular ATP on guinea pig ventricular myocytes because
      guinea pigs are a commonly used model for the study of cardiac electrophysiology.
      We have found that ATP activates a rapid, desensitizing, inward current. This
      inward current is activated by a P2 receptor that does not conform to published
      receptor subclasses. A concentration of 100 microM ATP activates more current
      than 100 microM alpha, beta-methyleneadenosine 5'-triphosphate, which in turn
      activates more current than 100 microM ADP. 2-Methylthioadenosine 5'-triphosphate
      (2-MeS-ATP) and adenosine 5'-O-(3-thiotriphosphate) are also effective agonists.
      Adenosine, AMP, guanosine 5'-triphosphate, and uridine 5'-triphosphate are
      ineffective at 100 microM. The inward conductance has a reversal potential near 0
      mV and in ion-substitution experiments was found to be carried through
      nonselective cation channels rather than chloride channels. The conductance has
      inwardly rectifying current-voltage (I-V) relations. When ATP is used as the
      agonist, fluctuation analysis yields an apparent unitary conductance of 0.08 pA
      at a holding potential of -120 mV with sodium as the main charge-carrying ion.
      The combination of inwardly rectifying I-V relations, the efficacy of 2-MeS-ATP,
      and the very low conductance distinguish this conductance from other ATP
      activated nonselective channels, including those recently cloned from rat vas
      deferens and PC-12 cells.

PMID- 7573518
TI  - Mechanisms of endotoxin-induced dilatation of cerebral arterioles.
AB  - Lipopolysaccharide (LPS; endotoxin) produces dilatation of cerebral arterioles in
      vivo which may be due, in part, to expression of inducible nitric oxide (NO)
      synthase. We tested the hypothesis that aminoguanidine, an inhibitor of inducible
      NO synthase, would reduce endotoxin-induced dilatation of cerebral arterioles.
      Because mechanisms other than expression of inducible NO synthase may contribute
      to endotoxin-induced dilatation of cerebral arterioles, we also tested the
      hypothesis that calcitonin gene-related peptide (CGRP) contributes to vascular
      responses to endotoxin. Cerebral arteriolar diameter was measured using a closed
      cranial window in anesthetized rabbits under control conditions [77 +/- 3 (SE)
      microns] and during topical application of endotoxin (100 micrograms/ml). After 4
      h, diameter of cerebral arterioles increased by 41 +/- 5%. Coapplication of
      aminoguanidine (0.3 mM) with endotoxin reduced vasodilatation at all time points
      (30 min to 4 h). Relative to control values, endotoxin treatment increased
      guanosine 3',5'-cyclic monophosphate (cGMP) concentration in cerebrospinal fluid
      (CSF) by approximately 20 fold at 4 h. Aminoguanidine attenuated the endotoxin
      induced increased in CSF cGMP concentration. Aminoguanidine (0.3 mM) did not
      alter acetylcholine-mediated dilatation of cerebral arterioles. Coapplication of
      CGRP-(8-37) (0.5 microM), a specific blocker of CGRP receptors, with endotoxin
      significantly reduced vasodilatation in response to endotoxin at 2, 3, and 4 h.
      Thus 1) aminoguanidine inhibits endotoxin- but not acetylcholine-mediated
      dilatation of cerebral arterioles, and 2) activation of CGRP receptors mediates a
      portion of endotoxin-induced dilation of cerebral arterioles.

PMID- 7573520
TI  - Transmembrane mechanochemical coupling in cardiac myocytes: novel activation of
      Gi by hyposmotic swelling.
AB  - We have studied the effect of hyposmotic swelling on adenosin 3',5'-cyclic
      monophosphate (cAMP) metabolism in isolated cardiac myocytes. Decreasing
      extracellular osmolarity by 12.5-50% results in graded inhibition (10-40%) of
      isoproterenol-stimulated and forskolin-stimulated cAMP accumulation but does not
      affect basal and hormone-stimulated phosphoinositide hydrolysis or cellular ATP
      content. Treatment with pertussis toxin does not alter the swelling response but
      abolishes the inhibitory effect of swelling on cAMP accumulation. The response to
      swelling seems not to involve the release of effectors known to couple to
      inhibitory G protein (Gi) in myocytes: BQ-123, atropine, and adenosine deaminase
      do not alter the inhibitory effect of swelling on isoproterenol-stimulated cAMP
      accumulation; conditioned medium from swollen cells, with restored osmolarity,
      has no effect on cAMP accumulation when added to control myocytes. In distinction
      to these effects on myocytes, swelling enhances hormone-stimulated cAMP
      accumulation in cultured S49 lymphoma cells. We conclude that swelling of cardiac
      myocytes inhibits cAMP accumulation through a mechanism that involves activation
      of a pertussis toxin-sensitive Gi protein. Activation of Gi by this means may
      contribute to adrenergic hyporesponsiveness in hypoxic and ischemic myocardium.

PMID- 7573521
TI  - Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit
      carotid artery to NO.
AB  - Endothelium-dependent relaxations to acetylcholine remain normal in the carotid
      artery of hypercholesterolemic rabbits, but unlike endothelium-dependent
      relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific
      blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the
      mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+
      channels directly or via guanosine 3',5'-cyclic monophosphate, the present study
      investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by
      NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc
      GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was
      measured in rabbit carotid artery denuded of endothelium from normal and
      hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under
      control conditions, relaxations to all agents were similar in normal and
      hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on
      relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the
      Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations
      caused by each of these agents in the arteries from hypercholesterolemic rabbits.
      By contrast, relaxations to the calcium channel blocker nifedipine were
      potentiated to a similar extent by charybdotoxin in both groups. In addition,
      arteries from hypercholesterolemic rabbits relaxed less than normal to sodium
      nitroprusside when contracted with depolarizing potassium solution. These results
      indicate that although nitrovasodilator relaxations are normal in the
      hypercholesterolemic rabbit carotid artery, they are mediated differently, and to
      a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that
      K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

PMID- 7573522
TI  - Losartan improves baroreflex control of heart rate of coarcted hypertensive rats.
AB  - To assess the role of angiotensin (ANG) II in both the increased heart rate (HR)
      and the impaired baroreceptor reflex control of HR that characterize the chronic
      phase of coarctation hypertension (CH), we compared basal HR, mean arterial
      pressure (MAP), and baroreflex sensitivity of coarcted hypertensive rats treated
      chronically with losartan, captopril, or vehicle. Baseline HR was recorded daily,
      and MAP and reflex HR changes and plasma renin activity (PRA) were measured in
      coarcted and sham-coarcted rats on the 5th day after coarctation. Both captopril
      (10 mg.kg-1.day-1 po) and losartan (10 mg.kg-1.day-1 po) caused a small
      nonsignificant reduction of hypertension (132 +/- 5 and 133 +/- 5, respectively,
      vs. 147 +/- 9 mmHg in vehicle-treated rats), but equally inhibited the late
      tachycardic phase (-37 +/- 13 and -29 +/- 12 beats/min in captopril- and losartan
      treated groups, respectively, vs. +79 +/- 19 beats/min in vehicle treated rats).
      Similar results were obtained for other groups of coarcted hypertensive rats
      after suppression of PRA by bilateral nephrectomy. Although hypertensive levels
      were the same during both treatments, only losartan given orally or
      intracerebroventricularlly (1.25 micrograms.kg-1.h-1) was effective in improving
      the reflex bradycardia. The depressed reflex tachycardia was corrected by chronic
      oral treatment with losartan. The data suggest that the tachycardia occurring in
      the chronic phase of CH is mediated by blood-borne ANG II and that the
      normalization of the reflex control of HR by losartan is achieved by blockade of
      type I receptors of ANG II in central areas accessible to oral or centrally
      administered losartan but not to oral captopril.

PMID- 7573524
TI  - Selective binding of platelet factor 4 to regions of active angiogenesis in vivo.
AB  - In a previous study we suggested that recombinant human platelet factor 4 (rhPF4)
      preferentially binds in vivo to regions of active angiogenesis/endothelial cell
      migration. To test this hypothesis, binding of fluorescently labeled rhPF4 to
      newly formed vessels was compared with that of the normal skin vasculature, using
      syngeneic Langerhans islets as inducers of angiogenesis. Islets were implanted in
      the dorsal skinfold chamber of the hamster, and the binding of rhPF4 was studied
      using intravital fluorescence microscopy. Intra-arterially injected rhPF4
      labeled, with high intensity, the endothelium along newly formed vessels of the
      islets (1,632 +/- 617 microns labeled vessel length per islet), and only on rare
      occasions (1 +/- 2 sites per cm2 skinfold) were short (62 +/- 48 microns) intense
      labeled sites found in the normal vasculature of the skinfold. Heparin could
      displace most of the label if injected within 10 min after the rhPF4 injection,
      but not 30 min after. In conclusion, rhPF4-preferentially binds to regions of
      active angiogenesis in vivo. On binding, rhPF4 is internalized as judged from a
      decreasing heparin sensitivity with time after rhPF4 injection. The infrequent
      rhPF4-labeling sites in the normal skin vasculature most likely represent regions
      of newly formed cells/migration, i.e., normal endothelial turnover, supporting
      our previous findings demonstrating that the occurrence of such regions is rare
      in the normal microvasculature. Furthermore, despite the previously demonstrated
      short half-life in plasma, systemically injected rhPF4 will target regions of
      angiogenesis with high affinity, thereby facilitating the antiangiogenic effect
      of PF4.

PMID- 7573523
TI  - Comparison of myocardial ATP, blood flow, and cytosolic adenosine in demand
      ischemia and coronary occlusion.
AB  - To investigate the relationship between flow and energy metabolism during
      coronary underperfusion, regional myocardial ATP content, cytosolic adenosine
      concentrations, and blood flow were measured during segmental coronary artery
      occlusion (complete ligation, n = 10) and demand ischemia (catecholamines plus
      atrial pacing with subtotal stenosis, n = 6) in halothane anesthetized open-chest
      dogs. During coronary occlusion or demand ischemia, L-homocysteine thiolactone
      was infused for 20 min, after which left ventricular tissue was rapidly frozen
      and analyzed for regional blood flow (microspheres) and content of ATP and S
      adenosylhomocysteine (SAH), an index of cytosolic adenosine. In nonischemic
      regions, ATP and SAH contents in both groups were the same as in unstimulated
      control animals with intact coronary circulation (n = 7), indicating that
      adrenergic stimulation during unrestricted flow had no effect on ATP or cytosolic
      adenosine. In the ischemic regions of both groups, there were decreases in
      regional flow, ATP content, and systolic wall thickening, and increases in SAH
      content. To compare the indexes of energy metabolism in tissue regions receiving
      equal blood flow, tissue samples were grouped into intervals of equal blood flow
      (ml.min-1.g-1). At every level of flow, ATP content in demand ischemia was 25-39%
      higher than in coronary occlusion. Estimates of cytosolic adenosine
      concentrations (using a mathematical model) in the lowest flow interval averaged
      5 microM in demand ischemia, approximately twice as high as in coronary
      occlusion. It is concluded that in tissue regions receiving equal blood flow, ATP
      was better maintained and cytosolic adenosine was higher in demand ischemia than
      in coronary occlusion. The differences in ATP content and cytosolic adenosine
      were not due to different blood flows but rather to more favorable energy
      metabolism in demand ischemia.

PMID- 7573528
TI  - Increase of cardiac work is associated with decrease of mitochondrial NADH.
AB  - In this study we investigated the effect of work and substrate supply on
      mitochondrial NADH/NAD+ using epicardial autofluorescence in rat hearts perfused
      according to Langendorff. To avoid vasoconstrictor effects during high work
      output, nitroprusside-containing Tyrode solution was used. Photobleaching was
      avoided by using discontinuous ultraviolet excitation for NADH fluorescence
      measurements. To increase work, heartbeat rate was raised from 5 to 7 Hz, and
      concomitantly left ventricular pressure was raised stepwise from 0 to +/- 90
      mmHg. During substrate-limited (5.5 mM glucose) perfusions, increase in O2
      consumption (3.5 +/- 0.4 mumol.min-1.g-1, mean +/- SE, n = 6) caused by increase
      of heartbeat rate was associated with a significant decrease of NADH fluorescence
      (-31 +/- 2.5%, mean +/- SE, n = 6). During perfusions with 10 mM pyruvate
      increase of O2 consumption (3.6 +/- 0.7 mumol.min-1.g-1, mean +/- SE, n = 6) was
      associated with significant decrease of NADH fluorescence (-20 +/- 2.6%, mean +/-
      SE, n = 6). These results suggest that a rise in mitochondrial NADH/NAD+ is not
      the primary stimulus for increase in respiration and that changes of
      mitochondrial NADH/NAD+ are secondary to changes in O2 consumption.

PMID- 7573530
TI  - Measurement of right ventricular volume by conductance catheter in closed-chest
      pigs.
AB  - This study details the effects of changes in right ventricular (RV) volume on the
      conductance catheter gain factor both over a broad volume range and within the
      cardiac cycle. In seven closed-chest anesthetized pigs, a conductance catheter
      was introduced transvenously and positioned to span the RV long axis, including
      the outflow tract. Parallel conductance was determined using a saline dilution
      technique. Conductance volume gain factor (alpha) was computed using stroke
      volume obtained by thermodilution over a range of volumes obtained by volume
      loading or sustained partial occlusion of the inferior caval vein. The chest was
      then opened, an ultrasonic flow probe was placed around the pulmonary artery, and
      the conductance-derived RV volume was compared with the pulmonary flow integral
      over the course of ejection. When volume was varied over a broad range, an
      inverse relation between RV volume and alpha was observed (P < 0.001). This did
      not cause significant nonlinearity of the conductance-volume relation. The
      relation was also relatively linear during the course of ejection within the
      cardiac cycle. These results indicate that the conductance catheter may be
      employed, using the described technique, to assess RV volume under steady-state
      conditions.

PMID- 7573525
TI  - Effect of aging and hypertension on contractility of resistance arteries:
      modulation by endothelial factors.
AB  - The effects of aging and hypertension on contraction were examined in rat
      mesenteric resistance arteries of 12- and 74-wk-old Wistar-Kyoto (WKY) and
      spontaneously hypertensive rats (SHR). The vessels were suspended in myographs
      (37 degrees C, 95% O2-5% CO2) filled with modified Krebs-Ringer bicarbonate
      solution. Isometric tension was measured. Contractions to KCl (100 mM) were
      similar in adult WKY and SHR; they increased in senescent WKY (P < 0.05) but
      decreased in senescent SHR (P < 0.05). Responses to norepinephrine (% of KCl)
      were comparable in all four groups. However, blockade of nitric oxide (NO)
      production with NG-nitro-L-arginine methyl ester (L-NAME) enhanced the
      sensitivity to norepinephrine in senescent animals, particularly in SHR.
      Inhibition of cyclooxygenase with indomethacin prevented increased sensitivity to
      norepinephrine after NO blockade. Responses to angiotensin (ANG) II were not
      affected by aging and hypertension, but the thromboxane receptor antagonist SQ
      30741 reduced ANG II-induced contractions only in SHR of both ages (P < 0.05).
      Aging increased responses to ANG I in SHR but decreased it in WKY (P < 0.05). In
      quiescent rings with endothelium, acetylcholine caused contractions in the
      presence of L-NAME in adult and senescent SHR but not in WKY (P < 0.05). SQ-30741
      prevented these contractions (P < 0.05). Contractions to the thromboxane analogue
      U-46619 were reduced only in senescent SHR (P < 0.05). Thus aging increases and
      hypertension decreases contractility of smooth muscle in rat mesenteric
      resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573527
TI  - The role of nitric oxide in the baroreceptor-cardiac reflex in conscious Wistar
      rats.
AB  - The role of nitric oxide (NO) in baroreceptor-cardiac reflex function was
      examined using a NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L
      NAME), in conscious Wistar rats. Mean arterial pressure (MAP) and heart period
      (HP) relationships were obtained by intravenous injection of graded doses of
      phenylephrine and sodium nitroprusside (SNP). The baroreflex function was
      compared before and after L-NAME (10 mg/kg iv), L-NAME (10 mg/kg iv) followed by
      exogenous NO supplied as SNP (10-20 micrograms.kg-1.min-1 iv), or SNP alone (20
      micrograms.kg-1.min-1 iv). To find the effect of changing basal MAP on baroreflex
      function, the baroreflex function was also examined before and after
      phenylephrine (8 micrograms.kg-1.min-1 iv) or L-NAME followed by concomitant
      infusion of SNP and phenylephrine. L-NAME increased basal MAP as well as HP from
      104 +/- 1 to 141 +/- 2 mmHg and from 168 +/- 3 to 237 +/- 7 ms, respectively. L
      NAME shifted the sigmoid curve in the direction of higher MAP with a significant
      increase in the gain (gain: control 2.14 +/- 0.15 ms/mmHg, L-NAME 3.70 +/- 0.26
      ms/mmHg, P < 0.001). L-NAME together with SNP infusion did not significantly
      affect the gain, basal MAP, or HP. Infusion of SNP alone shifted the sigmoid
      curve in the direction of lower MAP but had no significant effect on the gain. An
      infusion of phenylephrine or L-NAME with concomitant infusion of SNP and
      phenylephrine increased basal MAP similarly as L-NAME alone did but had no
      significant effect on the gain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573526
TI  - Endothelial dysfunction in a model of hyperglycemia and hyperinsulinemia.
AB  - Insulinopenic diabetes is known to produce endothelial dysfunction. This
      dysfunction could arise from either hyperglycemia or inadequate insulin. It is
      not known whether endothelial dysfunction occurs when hyperglycemia is present
      with elevated insulin levels. In this study, we utilized an experimental model of
      hyperglycemia with hyperinsulinemia to investigate latent endothelial
      dysfunction. Rats were continuously infused with glucose or saline for 72 h to
      achieve peak plasma glucose concentrations of approximately 25 mM. Plasma insulin
      rose by 12-fold in glucose-infused rats. No significant differences in serum
      electrolyte concentration were noted between control and glucose-infused rats
      after 72 h. Blood pressure was not altered by this intervention. Aortic rings
      taken from control rats relaxed to the endothelium-dependent vasodilators,
      acetylcholine and A-23187, and to the endothelium-independent vasodilator,
      nitroglycerin. Relaxation to acetylcholine but not to A-23187 or nitroglycerin
      was impaired in glucose-infused rat aortic rings. Incubation in vitro with either
      indomethacin or superoxide dismutase did not restore the impaired relaxation to
      acetylcholine in rings taken from glucose-infused rats. Thus hyperglycemia with
      hyperinsulinemia selectively impairs receptor-dependent, endothelium-dependent
      relaxation. These studies suggest that elevated glucose may be a common pathway
      leading to endothelial dysfunction in insulin-dependent diabetes mellitus and
      hyperglycemia-induced insulin resistance.

PMID- 7573529
TI  - Inhibition of collagen cross-linking: effects on fibrillar collagen and
      ventricular diastolic function.
AB  - The fibrillar collagen network is postulated to be a primary determinant of left
      ventricular diastolic stiffness. This hypothesis was tested by examining the
      structural and physiological effects of a reduction in fibrillar collagen content
      and cross-linking in the intact left ventricle. Collagen cross-linking was
      inhibited by treating five normal adult pigs with beta-aminopropionitrile (BAPN;
      10 g/day po) for 6 wk; five normal untreated pigs served as controls. Left
      ventricular volume, mass, and function were determined by simultaneous
      echocardiography and catheterization. Chamber stiffness, defined by pressure vs.
      volume data, and myocardial stiffness, defined by stress vs. dimension data, were
      determined from variably loaded beats during dextran infusion. Collagen
      distribution (% area) and integrity (% confluence) were determined by light
      microscopy. Collagen content was measured by hydroxyproline assay, and collagen
      cross-linking was measured by salt extraction. BAPN decreased collagen
      distribution (% area decreased from 12 +/- 1% in control to 7 +/- 1% in BAPN, P <
      0.05), collagen integrity (% confluence decreased from 8 +/- 1% in control to 4
      +/- 1% in BAPN, P < 0.05), collagen content (from 36 +/- 2 mg/g dry wt in control
      to 27 +/- 2 mg/g dry wt in BAPN, P < 0.05), and collagen cross-linking
      (extractable collagen increased from 21 +/- 2% in control to 28 +/- 2% in BAPN, P
      < 0.05). BAPN decreased chamber stiffness (0.13 +/- 0.02 in control to 0.06 +/-
      0.01 in BAPN, P < 0.05) and myocardial stiffness (10.4 +/- 0.5 in control to 6.6
      +/- 0.5 in BAPN, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573532
TI  - Ischemia- and reperfusion-sensitive cardiac sympathetic afferents: influence of
      H2O2 and hydroxyl radicals.
AB  - Activation of cardiac sympathetic afferents leads to excitatory cardiovascular
      reflexes and pain during myocardial ischemia. We hypothesized that cardiac
      sympathetic afferents are activated by reactive oxygen species produced during
      ischemia and reperfusion. Single-unit nerve activity of 55 afferents was recorded
      from the left paravertebral sympathetic chain (T1-T4) in cats anesthetized with
      alpha-chloralose. Receptive fields of all afferents were located on the right or
      left ventricle. Mechanical and chemical sensitivities of each afferent ending
      were evaluated by von Frey hairs, cardiac distension, and local application of
      bradykinin (BK, 142 pmol) or H2O2 (7.5-15 mumol) to the receptive field. Thirty
      one afferents (56%) were responsive to bradykinin (BK), H2O2, and ischemia (2 or
      10 min). Deferoxamine (Def, 10-100 mg/kg), dimethylthiourea (DMTU, 10-100 mg/kg),
      or iron-loaded Def (10 mg/kg) were employed to evaluate the role of H2O2 and
      hydroxyl radicals (.OH) in activating these afferents (10A delta and 21C fibers)
      during ischemia and reperfusion. Treatment with the nonspecific scavenger DMTU (n
      = 10) significantly diminished the increase in discharge activity evoked by
      ischemia and reperfusion. Treatment with Def also significantly attenuated the
      responses during ischemia and reperfusion. Thus reactive oxygen species,
      particularly .OH, activate a group of cardiac sympathetic A delta- and C-fiber
      afferents during myocardial ischemia and reperfusion and may play an important
      role in mediating cardiovascular sympathetic reflex responses and/or pain
      transmission.

PMID- 7573535
TI  - Effect of L-NMMA, cromakalim, and glibenclamide on cerebral blood flow in
      hypercapnia and hypoxia.
AB  - Sulfonylureas reduce cerebral blood flow (CBF) during hypoxia but not during
      hypercapnia, whereas blockers of nitric oxide (NO) synthesis reduce hypercapnic
      CBF. However, the effect of NO blockers on hypoxic CBF is uncertain. CBF was
      measured in the cortex of 51 enflurane-anesthetized rats by the hydrogen
      clearance technique during eucapnia, hypercapnia (arterial PCO2 65 Torr), and
      hypoxia (arterial PO2 40 Torr). CBF increased twofold in both hypercapnia and
      hypoxia from eucapnia. Intracortical (ic) NG-monomethyl-L-arginine (L-NMMA, 100
      microM-5 mM) attenuated both the hypercapnic and hypoxic dilations by 60-70%, and
      L-arginine (300 mg/kg iv) partially reversed these effects. Glibenclamide (10
      microM ic) and L-NMMA gave no further attenuation of the hypoxic dilation than L
      NMMA alone. Cromakalim (10 microM, ic) increased CBF in eucapnia, but this was
      not seen in the presence of glibenclamide. The adenosine antagonist 8-phenyl
      theophylline did not attenuate the hypoxic dilation. This suggests that NO
      synthesis plays a major role in the regulation of CBF in hypercapnia and hypoxia.
      But the combined effects of glibenclamide and L-NMMA do not further attenuate CBF
      in hypoxia.

PMID- 7573534
TI  - Determinants of respiratory sinus arrhythmia in the vagotomized rabbit.
AB  - After cardiac denervation, a small-amplitude respiratory sinus arrhythmia (RSA)
      has been described in animals and humans. Its mechanical and chemical
      determinants were investigated in 19 urethan-anesthetized, vagotomized, and
      mechanically ventilated rabbits. We measured the influence on RSA of arterial
      blood gases, beta-adrenergic blockade, and phasic and steady changes in right
      atrial pressure (RAP) induced by changes in tidal volume (VT, 20, 40, 60 ml),
      respiratory frequency (RF, 10, 20, 30 cycles/min), and dextran-induced RAP
      increases. Phasic changes in RAP during each recording were quantified as
      standard deviation of the first derivative of the RAP signal (dRAP) as a measure
      of magnitude of variations of the rate of change due to respiration. RSA was
      assessed by combined autoregressive power spectral analysis of R-R interval and
      respiration on sequences of 256 heart-beats. Despite vagotomy, RSA was present in
      all recordings in all animals. During room air breathing, RSA changes were
      dependent on RF and VT (P < 0.025 and P < 0.001, respectively) and correlated
      with dRAP (P < 0.001) and arterial PO2 (P < 0.001). beta-Adrenergic blockade did
      not change the amplitude of this residual RSA or its dependence on ventilatory
      mechanics. Dextran-induced increase in mean RAP from 2.9 to 11.9 mmHg did not
      modify RSA or dRAP. During 100% O2 inhalation, RSA changes were no longer
      significantly linked to RF and VT, and also the correlation of RSA with dRAP was
      reduced (P < 0.05). Changing the arterial PCO2 from 28 to 79 mmHg (induced by
      increasing dead space at fixed ventilation) did not modify RSA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573537
TI  - Effects of atrial pacing site on rate-dependent AV nodal function in rabbit
      hearts.
AB  - The functional origin of the changes in atrioventricular (AV) nodal function with
      the atrial pacing site was studied in isolated rabbit heart preparations. The
      rate-dependent AV nodal properties of recovery, facilitation, and fatigue were
      characterized with premature stimulation protocols repeated for each of three
      atrial pacing sites (upper atrium, low crista terminalis, and low interatrial
      septum). The effects of the atrial pacing site, reference site from which the
      beginning of nodal activation is measured (low crista and low septum) and
      stimulation protocol on nodal conduction and refractory parameters, were assessed
      with multifactorial analyses of variance. The changes in nodal parameters with
      the stimulation protocol did not differ significantly with the pacing site,
      indicating that the rate-dependent nodal properties are not affected by the
      atrial origin of the impulse. Only the baseline value of nodal parameters varied
      with the atrial pacing and reference site. However, the comparison of data
      obtained while the low crista was the pacing and reference site to those obtained
      while the low septum was the pacing and reference site yield no statistically
      significant differences, thus indicating that changes in perinodal activation
      were largely responsible for the observed changes in baseline. Upper atrial and
      low crista pacing yielded very similar data. We conclude that 1) the atrial
      pacing site affects perinodal activation but not rate-dependent nodal function,
      2) the two inputs are equally effective in activating the AV node, and 3) input
      summation is a minor factor in rate-dependent nodal function.

PMID- 7573533
TI  - Downregulation of atrial natriuretic factor clearance receptors in experimental
      chronic renal failure rats.
AB  - Studies were performed to examine the changes of renal ANF second messenger
      guanosine 3',5'-cyclic monophosphate (cGMP) responses and receptor properties in
      chronic renal failure (CRF). Five-sixths-nephrectomized and sham-operated Wistar
      rats were used. The glomerular filtration rate was decreased in the five-sixths
      nephrectomized rats, which also had significantly higher plasma blood urea
      nitrogen and plasma atrial natriuretic factor (ANF) levels (148.5 +/- 10.2 vs.
      115.7 +/- 7.3 pg/ml, P = 0.01) than the sham rats. In vitro ANF-stimulated cGMP
      accumulations in glomeruli of five-sixths-nephrectomized rats were higher than
      controls. Radioligand-binding experiments showed downregulation of the total ANF
      receptor in both acid and nonacid wash CRF glomeruli (nonacid wash: 189 +/- 25
      vs. 362.8 +/- 52.8 fmol/mg protein, P < 0.05; acid wash: 449.8 +/- 67 vs. 652.7
      +/- 52.5 fmol/mg protein, P < 0.05). No change in receptor densities was observed
      in the des(Gln18,Ser19,Gly20,Leu21)atrial natriuretic peptide-(4--23)-NH2
      resistant receptors between sham and CRF rat glomeruli. Therefore, downregulation
      of ANF clearance receptors exists in CRF rat glomeruli, and this is associated
      with the exaggerated ANF-stimulated cGMP response in these CRF glomeruli.
      Hypersensitivity of CRF rat to ANF, together with high plasma ANF levels and
      downregulation of clearance receptor, may contribute to increased sodium
      excretion in CRF.

PMID- 7573536
TI  - Cardiac rhythmicity among NTS neurons and its relationship to sympathetic outflow
      in rabbits.
AB  - The caudal nucleus tractus solitarius (NTS) is the primary termination site for
      baroreceptor afferents, but distinct pulse phasic activity is rarely recorded
      from NTS neurons. In the present study cross-correlation analysis was used to
      identify pulse phasic activity in NTS neurons in the anesthetized rabbit. Cross
      correlation analysis demonstrated that 19 of 38 pressure-sensitive neurons had
      activity that correlated with the cardiac cycle, including 5 of 11 neurons
      activated by aortic depressor nerve stimulation, and 12 of 28 pressure-sensitive
      NTS neurons had activity that correlated with renal sympathetic nerve activity.
      Autocorrelation analysis identified 17 of 38 pressure-sensitive neurons that had
      rhythmic activity not related to the cardiac cycle (mean frequency 14.1 +/- 2
      Hz). The results indicate that many NTS neurons do have pulse phasic activity
      consistent with baroreceptor input, but this activity is difficult to detect
      because it is distributed throughout the cardiac cycle.

PMID- 7573531
TI  - Primary negativity does not predict dominant pacemaker location: implications for
      sinoatrial conduction.
AB  - Activation sequence maps derived during normal sinus rhythm from extracellular
      potentials in the canine right atrium exhibit widely separated sites of origin.
      The objectives of this study were to characterize the distribution of pacemakers
      within the right atrium and to determine the relationship of pacemaker action
      potentials to sites of earliest surface activation as well as to local
      extracellular electrograms. The right atria of six adult mongrel dogs were
      rapidly excised under deep pentobarbital sodium anesthesia and perfused with 95%
      O2-5% CO2 Krebs-Henseleit solution. Action potentials from the epicardial surface
      were recorded throughout the region bounded by the crista terminalis laterally
      and the atrial septum medially. Simultaneously, unipolar extracellular
      electrograms were recorded from 250 endocardial sites. The earliest pacemakers
      preceded the earliest electrogram by 63 +/- 34 ms; the latest pacemakers followed
      the earliest electrogram by 71 +/- 40 ms. Primary negativity in the extracellular
      electro gram did not predict the site of the earliest or dominant pace maker and
      in some cases was associated with the latest pace makers. We conclude that
      primary negativity and/or the sites of earliest activation reflect the point at
      which the impulse engages atrial myocardium, not the site of earliest pacemaker
      activity. As such, early extracellular activation appears to represent sites of
      exit from a relatively insulated sinus node.

PMID- 7573538
TI  - Fibroblast proliferation during myocardial development in rats is regulated by
      IGF-1 receptors.
AB  - To determine whether the growth of cardiac fibroblasts during development is
      modulated by the insulin-like growth factor (IGF)-1 receptor (IGF-1R), the
      expression of IGF-1, IGF-2, and IGF-1R was determined in fibroblasts from fetal
      and postnatal hearts. The expression of proliferating cell nuclear antigen (PCNA)
      and DNA polymerase-alpha was also evaluated in combination with the estimation of
      DNA replication. In comparison with fetal hearts, at postnatal day 21, fibroblast
      expression of IGF-1R mRNA, IGF-2, PCNA, and DNA polymerase-alpha was reduced by
      77, 70, 80, and 86%, respectively. Moreover, IGF-1R protein decreased by 48% at
      21 days. Bromodeoxyuridine labeling decreased by 88 and 89% in the left and right
      ventricle, respectively, at this time. Two different antisense
      oligodeoxynucleotides to IGF-1R reduced DNA replication by 60 and 44% in
      fibroblasts in culture. In addition, this intervention markedly attenuated the
      growth response of fibroblasts to IGF-1 or serum. In conclusion, the IGF-1R
      system appears to play a major role in the regulation of fibroblast growth in the
      heart in vivo.

PMID- 7573539
TI  - Cardiorespiratory transfer during sleep: a study in healthy young men.
AB  - This study tested the concept that changes in breathing parameters account for
      modifications in respiratory-related blood pressure (BP) and R-R interval (RRI)
      variability during nocturnal sleep. BP (Finapres), electrocardiogram, respiration
      (Respitrace), and polygraphic sleep recordings were recorded continuously in 13
      healthy men aged 18-37 yr. The transfer characteristics identified by coherence
      and gain measures between the calibrated thoraco-abdominal motion and the
      respiratory-related BP and RRI variability evidenced a consistent increase during
      transitions from wake to light sleep and from light to deep sleep but returned to
      waking levels during rapid-eye-movement sleep (P < 0.0001). These changes were
      related to the specific modifications occurring in the respiratory rate, tidal
      volume, and ribcage-to-abdominal motion ratio during the different sleep stages
      (0.28 < r < 0.39; P < 0.0001). This study demonstrates 1) that modifications in
      the breathing pattern account for 8-15% of the variance in the cardiorespiratory
      transfer, and 2) that respiratory modulation of vagal activity is not the main
      mechanism controlling the magnitude of the respiratory-related BP and RRI
      variability during sleep.

PMID- 7573540
TI  - Different effects of histamine H1 and H2 stimulation on left ventricular
      contractility in pigs.
AB  - Histamine decreases ventricular contractility in some settings but increases it
      in others. To better understand these apparently discrepant results, we measured
      hemodynamics and left ventricular pressure (Millar catheter) and volume
      (ultrasonic crystals) in atrially paced, alpha- and beta-antagonist-treated pigs.
      Histamine was infused (0.5-10 micrograms.kg-1.min-1) before and after H2
      antagonist (ranitidine) pretreatment. Changes in left ventricular contractile
      function were measured as shift of the end-systolic pressure-volume relationship
      (delta ESPVR) at a pressure of 100 mmHg. We found that at low doses (0.5 and 1
      micrograms.kg-1.min-1), histamine significantly decreased delta ESPVR (-1.1 +/-
      1.4 ml, P < 0.05) after H2-antagonist pretreatment. At doses above 1
      micrograms.kg-1.min-1, histamine increased contractility in a dose-response
      fashion [maximum effect: 5.1 +/- 3.3 ml, dose resulting in 50% effect (ED50):
      0.75 +/- 1.79 micrograms.kg-1.min-1] that was best described using a Hill
      coefficient of 2. Ranitidine increased the ED50 by approximately one order of
      magnitude (0.75 +/- 1.79 to 9.50 +/- 2.60 micrograms.kg-1.min-1, P < 0.05). We
      conclude that in vivo, at higher doses, histamine increases left ventricular
      contractility via H2-receptor stimulation, whereas at low doses histamine
      decreases left ventricular contractility, probably via H1-receptor stimulation.

PMID- 7573541
TI  - Sarcoplasmic reticulum in cardiac length-dependent activation in rabbits.
AB  - After a step increase in length of rabbit right ventricular papillary muscles,
      active stress increased immediately followed by a further slow increase in stress
      over 15-20 min. We studied the contribution of the sarcoplasmic reticulum (SR) to
      the slow change in stress (SCS) after changing muscle length from 85 to 95% of
      length at which active force development was maximal. SCS amounted to 32.5 +/-
      12.2% mean +/- SD, n = 19) of the total increase in active stress. This was
      associated with a 13.2 +/- 8.7% increase in calcium content of the SR as
      estimated with rapid cooling contractures (P < 0.0001, n = 19). However, SCS was
      not dependent on SR calcium content. There was no significant attenuation in SCS
      after SR calcium depletion with ryanodine (n = 6), SR Ca(2+)
      adenosinetriphosphatase inhibition with cyclopiazonic acid (n = 6), or combined
      treatment with ryanodine and cyclopiazonic acid (n = 3). We conclude that, in the
      rabbit, SR calcium content increases slowly after a step increase in cardiac
      muscle length but the slow changes in active stress are not dependent on the
      sarcoplasmic reticulum.

PMID- 7573542
TI  - Diastolic time: an important determinant of regional arterial blood flow.
AB  - In unanesthetized dogs we measured heart rate, blood pressure, and external
      iliac, celiac, and renal artery flows on a beat-by-beat basis. All three flows
      fluctuated in synchrony with breathing. Although the fluctuations in renal flow
      could to a large degree be explained by fluctuations in blood pressure, this was
      not the case in the external iliac artery where flow increased when pressure
      decreased and decreased when pressure increased. These paradoxical fluctuations
      in flow appear to be caused by respiratory fluctuations in heart rate, since we
      observed a strong (r = 0.89) correlation between external iliac flow and the
      length of the preceding diastole. Single long diastolic periods, induced by
      atropine, were always followed by a beat of increased flow even though arterial
      pressure was constant. We conclude that diastolic time has a profound impact on
      blood flow during the next beat. Our data support a model of the arterial system
      in which backpressure to flow through a bed is dependent on the amount of time
      for diastolic runoff into the capillaries.

PMID- 7573544
TI  - Evidence for NO involvement in regulating vascular reactivity in balloon-injured
      rat carotid artery.
AB  - The present study evaluated the influence of this newly formed intima on vascular
      reactivity in balloon-injured carotid arteries and the regulatory role of the
      vasodilator, nitric oxide (NO). Balloon injury was performed using a 2-F Fogarty
      catheter. After 2 and 4 wk, carotid artery segments were removed for both
      histomorphometric analysis and determination of in vitro contractile responses.
      Histomorphometric analysis showed a marked intimal thickening with an intima-to
      media ratio of 126 +/- 19% (n = 5). The lack of factor VIII staining in injured
      carotid arteries revealed the absence of endothelium, since factor VIII-related
      antigen is a glycoprotein synthesized by endothelial cells. Functionally, maximal
      contractile responses to norepinephrine, angiotensin II (ANG II), endothelin-1,
      and serotonin were all attenuated in the injured vessels compared with the
      uninjured carotid arteries [0.38 +/- 0.11 vs. 0.73 +/- 0.10 g (n = 5),
      norepinephrine; 0.15 +/- 0.06 vs. 0.38 +/- 0.05 g (n = 4), ANG II; 0.60 +/- 0.14
      vs. 1.05 +/- 0.12 g (n = 4), endothelin-1; 0.23 +/- 0.07 vs. 0.60 +/- 0.06 g (n =
      12), serotonin]. Contractile responses induced by KCl were not affected by the
      balloon injury (0.62 +/- 0.10 vs. 0.64 +/- 0.09 g, n = 4). Interestingly,
      carbachol, a muscarinic agonist and vasodilator, caused concentration-dependent
      relaxations in 2- as well as 4-wk postinjured vessels despite the absence of
      endothelium. The NO synthase inhibitors, N omega-L-arginine methyl ester (L-NAME)
      and N omega-nitro-L-arginine (L-NNA), blocked the relaxation responses evoked by
      carbachol. Exogenously administered L-arginine reversed this blockade of the NOS
      inhibitors on the carbachol-induced relaxations. In addition, L-NAME partially
      reversed in a concentration-dependent manner the reduced maximal contractile
      force elicited by serotonin in the injured carotid artery.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7573545
TI  - Opioids contribute to hypoxia-induced pial artery dilation through activation of
      ATP-sensitive K+ channels.
AB  - It has been previously observed that hypoxia increases cerebrospinal fluid (CSF)
      methionine enkephalin and leucine enkephalin levels, and these opioids contribute
      to hypoxia-induced pial artery vasodilation. The present study was designed to
      investigate whether the activation of ATP-sensitive K+ channels (KATP) mediates
      the contribution of opioids to the hypoxia-induced pial artery dilation. The
      closed-cranial window technique was used to measure pial diameter in newborn
      pigs. Glibenclamide (10(-6) M), a KATP inhibitor, attenuated the dilation
      resulting from moderate and severe hypoxia [23 +/- 1 and 33 +/- 2% vs. 7 +/- 1
      and 18 +/- 2%, respectively, for moderate and severe hypoxia (arterial PO2
      approximately 35 and 25 mmHg, respectively) in the absence vs. presence of
      glibenclamide]. In addition, glibenclamide attenuated the dilation produced by
      methionine enkephalin (10(-8) and 10(-6) M) (13 +/- 1 vs. 4 +/- 2% and 21 +/- 2
      vs. 7 +/- 3%, respectively, for methionine enkephalin in the absence and presence
      of glibenclamide). Leucine enkephalin-induced dilation was similarly attenuated
      by glibenclamide. Cromakalim (10(-8) and 10(-6) M), a KATP agonist, produced
      dilation that was blocked by glibenclamide (12 +/- 1 and 25 +/- 1 vs. 3 +/- 1 and
      5 +/- 1% before and after glibenclamide, respectively). These data show that
      activation of KATP contributes to methionine enkephalin- and leucine enkephalin
      induced dilation. Furthermore, these observations suggest that opioids contribute
      to hypoxia-induced pial artery dilation via KATP activation.

PMID- 7573543
TI  - Cardiac myocytes release leukocyte-stimulating factors.
AB  - The production of cytokines directly from cardiac myocytes has not been
      previously demonstrated and could represent an important mechanism and site of
      intervention in ischemia and reperfusion injuries. Macrophage inflammatory
      protein-2 (MIP-2) and monocyte chemotactic protein (MCP) are chemotactic
      cytokines (chemokines) that stimulate polymorphonuclear leukocytes (PMNs) and
      monocytes, respectively. Endothelium has been implicated as being a major
      cellular source of leukocyte-activating factors. We hypothesized that the
      myocardial cells may also play an important role in producing chemokines
      independently of endothelium. Primary cultures of adult rat ventricular myocytes
      were prepared. Cultured myocytes were stimulated with either interleukin 1 (IL
      1), tumor necrosis factor (TNF), or lipopolysaccharide (LPS). MIP-2 and MCP mRNA
      were expressed in adult rat myocytes following stimulation. Our studies indicate
      that ventricular myocytes expressed chemokine mRNA and protein in both a dose-
      and time-dependent fashion. MIP-2 and MCP release, determined by enzyme-linked
      immunosorbent assay, was biologically active, accounting for approximately 40% of
      the PMN and monocyte chemotactic activity produced by these cells. These results
      suggest that cardiac myocytes may directly recruit activated leukocytes into
      areas of injury. Such a recruiting process could underlie the migration of
      leukocytes into areas of oxidant stress and play a role in development of
      reperfusion injury of myocardium.

PMID- 7573546
TI  - ACE inhibition prevents Na and water retention and MABP increase during reduction
      of renal perfusion pressure.
AB  - Two groups of six dogs were studied during 4 control days and 4 days of reduced
      renal perfusion pressure (rRPP) servo controlled at 20% below the individual
      dog's 24-h mean arterial blood pressure (MABP) during control days, i.e., below
      the threshold for renin release. On rRPP days, endogenous activation of plasma
      aldosterone and angiotensin II was inhibited by the angiotensin-converting enzyme
      inhibitor captopril. The dogs were kept on a high-Na and high-water intake.
      Unlike studies during rRPP alone, there was no Na and water retention during
      rRPP+captopril. Glomerular filtration rate dropped by approximately 9%, and MABP
      remained in the range of control days. Plasma renin activity rose to values 14
      times greater than control, whereas plasma aldosterone decreased by approximately
      60%. Atrial natriuretic peptide remained in the range of controls. In conclusion,
      angiotensin-converting enzyme inhibition can prevent the otherwise obligatory Na
      and water retention and systemic MABP increase during a 20% reduction in renal
      perfusion pressure. This is achieved most likely via the captopril-induced fall
      in angiotensin II and plasma aldosterone levels.

PMID- 7573547
TI  - Intestinal absorption of water-soluble vitamins in channel catfish (Ictalurus
      punctatus).
AB  - The absorption of selected water-soluble vitamins was studied in isolated
      intestinal sleeves of channel catfish (Ictalurus punctatus). The uptakes of
      riboflavin and biotin were each inhibited by their nonlabeled form, indicating
      the presence of a saturable mechanism [riboflavin: Michaelis constant (Km), 4.84
      +/- 1.23 microM; maximal velocity (Vmax), 0.59 +/- 0.07 pmol.mg-1.min-1 biotin:
      Km, 22.3 +/- 6.95 microM; Vmax, 0.67 +/- 0.10 pmol.mg-1.min-1]. In contrast, the
      uptakes of nicotinamide, folic acid, and its metabolic derivative 5
      methyltetrahydrofolate were not significantly inhibited by their respective
      nonlabeled forms. Their uptakes were a linear function of concentration
      [dissociation constant, 0.173 +/- 0.006, 0.050 +/- 0.002, and 0.031 +/- 0.004
      pmol.mg-1.min-1.microM-1, respectively]. Folic acid was absorbed more rapidly
      than 5-methyltetrahydrofolate, and neither vitamin inhibited the absorption of
      the other. Intestinal uptake of riboflavin and biotin is carrier mediated,
      whereas uptake of nicotinamide, folic acid, and 5-methyltetrahydrofolate occurs
      by simple diffusion. These mechanisms are similar to those found in mammals for
      the same vitamins, except for the hydrophobic folates, which are actively
      transported in mammals but where diffusion may suffice to fulfill metabolic
      requirements of catfish.

PMID- 7573548
TI  - Fundus striati vasopressin receptors in blood pressure control.
AB  - Vasopressin (VP), given intracerebrally to rats, can induce antipyresis, motor
      disturbances, and increases in arterial blood pressure. The possibility that the
      VP-binding sites in the fundus striati (FStr) could participate in these effects
      was investigated. After a bilateral injection of 100 pmol of VP into the FStr,
      the fever induced by an injection of the lipopolysaccharide of Escherichia coli
      (50 micrograms/kg ip) was not affected. Bilateral injections of 100 pmol of VP
      did not induce motor disturbances or alterations in body temperature after either
      of two successive injections. In contrast, bilateral injections of VP into
      urethan-anesthetized rats induced dose-dependent increases in arterial pressure
      without affecting heart rate. This increase was blocked by a V1 antagonist;
      oxytocin and a V2 agonist were ineffective. In keeping with this preliminary
      pharmacological analysis, radio-ligand-binding studies of the FStr revealed
      binding sites in the FStr exhibiting a binding profile typical of the V1 subtype.
      This study suggests that the V1 receptors in the FStr could participate in the
      central regulation of the blood pressure.

PMID- 7573550
TI  - Galanin and the galanin antagonist M40 do not change fat intake in a fat-chow
      choice paradigm in rats.
AB  - The neuropeptide galanin has been proposed to play a role in the regulation of
      fat intake. The purpose of the present investigation was to determine if galanin
      and the galanin receptor antagonist M40 would have selective effects on fat
      intake in a fat-chow choice paradigm in rats. Rats were adapted to 22-h access to
      chow alone and 2-h daily access to separate sources of fat and chow in the early
      dark cycle. Galanin (300 pmol, 1 nmol) or M40 (2-500 pmol) was microinjected
      bilaterally into the paraventricular nucleus of the hypothalamus (PVN) before the
      2-h choice period, and chow and fat intake were measured. M40 had no effect on
      chow or fat intake. Galanin stimulated chow intake and increased the ratio of
      chow to fat consumed but had no significant effect on fat intake alone. These
      results suggest that endogenous galanin in the PVN may not play a primary role in
      the regulation of fat intake when fat is available in addition to a nutritionally
      balanced diet.

PMID- 7573551
TI  - Regulation of beta 3-adrenergic receptor mRNA by sympathetic nerves and
      glucocorticoids in BAT of Zucker obese rats.
AB  - Impaired brown adipose tissue (BAT) thermogenesis in the genetically obese Zucker
      fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the
      role of the sympathetic nervous system in modulating the effects of adrenalectomy
      by studying beta3-adrenergic receptor (AR) and uncoupling protein (UCP) mRNA
      levels in unilaterally sympathectomized interscapular BAT of lean and obese rats.
      UCP mRNA levels were increased by adrenalectomy. Sympathetic denervation
      prevented this adrenalectomy-induced increase in lean rats but not in obese rats.
      beta 3-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decreased and
      denervation increased beta 3-AR mRNA in lean rats but the opposite response was
      observed to both of these manipulations in obese rats. beta 3-AR mRNA and UCP
      mRNA were negatively correlated in lean rats but positively correlated in obese
      rats. Norepinephrine increased UCP mRNA levels in denervated BAT of both lean and
      obese rats and decreased beta 3-AR mRNA in lean rats but not obese rats. These
      data suggest that the regulation of the beta 3-AR gene in response to sympathetic
      stimuli and glucocorticoids is abnormal in the obese rat.

PMID- 7573552
TI  - Multiple mechanisms mediate antipyretic action of glucocorticoids.
AB  - Glucocorticoids inhibit various components of the acute phase response,
      particularly the increase in body temperature (fever) induced by a variety of
      stimuli. In the present study these observations have been extended, and we have
      determined the effect of glucocorticoid treatment or surgical adrenalectomy on
      the cytokine and prostaglandin (PG) concentrations in plasma and cerebrospinal
      fluid (CSF) during the febrile response to endotoxin. Dexamethasone treatment,
      either before or after endotoxin injection, markedly inhibited fever and the
      increased plasma interleukin (IL)-6 and CSF IL-6, PGE2, and PGF2 alpha
      concentrations. Adrenalectomized (ADX) rats showed higher fevers and plasma and
      CSF IL-6, PGE2, and PGF2 alpha, concentrations compared with sham-operated
      animals and exhibited a lower plasma-to-CSF IL-6 ratio than sham-operated
      animals. Dexamethasone pretreatment also inhibited fever induced by centrally
      injected TNF-alpha, IL-1 beta, or IL-6. Pyrogenic response to IL-8 was not
      modified by indomethacin but was markedly inhibited by prior treatment with
      dexamethasone. These results support the hypothesis that endogenous
      glucocorticoids function as part of an inhibitory feedback system involved in the
      modulation of fever and that multiple mechanisms may be involved in their
      antipyretic effect.

PMID- 7573549
TI  - Interactions between angiotensin and nitric oxide in the renal response to volume
      expansion.
AB  - This study examined, in anesthetized dogs, the possible interactions between
      nitric oxide (NO) and angiotensin II (ANG II) in mediating the renal response to
      an extracellular volume expansion (ECVE). It was found that the intrarenal
      maintenance of ANG II levels (group 1) or the intrarenal NO synthesis inhibition
      (group 2) did not induce changes in renal hemodynamics but reduced (P < 0.05) the
      ECVE-induced increments in sodium excretion and fractional lithium excretion
      (FeLi). In the third group, ANG II synthesis was inhibited during NO synthesis
      blockade. It was found in this group that the NO synthesis inhibition reduced the
      ECVE-induced increment in sodium excretion (P < 0.05) but did not modify the ECVE
      induced increment in FeLi. These results suggest that the increase of proximal
      sodium reabsorption induced by the No synthesis inhibition is mediated by
      endogenous ANG II levels. In the fourth group, it was observed that NO synthesis
      inhibition, during the intrarenal maintenance of ANG II levels, induced a
      decrease of renal blood flow (P < 0.05) and reduced the natriuretic response to
      ECVE to a lower level (P < 0.05) than that observed in groups 1 and 2. The
      results of this group suggest that endogenous NO modulates the vasoconstrictor
      and antinatriuretic effects of ANG II during an ECVE. In summary, the results of
      this study suggest that there is an important interaction between NO and ANG II
      in mediating the renal response to an ECVE.

PMID- 7573553
TI  - Resistance exercise-induced fluid shifts: change in active muscle size and plasma
      volume.
AB  - The purpose of this study was to test the hypothesis that the reduction in plasma
      volume (PV) induced by resistance exercise reflects fluid loss to the
      extravascular space and subsequently selective increase in cross-sectional area
      (CSA) of active but not inactive skeletal muscle. We compared changes in active
      and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance
      imaging (MRI) was used to quantify muscle involvement in exercise and to
      determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add),
      hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was
      determined using exercise-induced contrast shift in spin-spin relaxation time
      (T2)-weighted MR images immediately postexercise. Alterations in muscle size were
      based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans
      blue dye were used to estimate changes in PV. Muscle CSA and PV data were
      obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A
      hierarchy of muscle involvement in exercise was found such that VS > Add > Ham >
      RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add
      muscle groups were increased 10 and 5%, respectively, immediately after exercise
      in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately
      following exercise. The absolute loss of PV was correlated (r2 = 0.75) with
      absolute increase in muscle CSA immediately postexercise, supporting the notion
      that increased muscle size after resistance exercise reflects primarily fluid
      movement from the vascular space into active but not inactive muscle.

PMID- 7573554
TI  - Effect of diet on insulin- and contraction-mediated glucose transport and uptake
      in rat muscle.
AB  - A diet rich in fat diminishes insulin-mediated glucose uptake in muscle. This
      study explored whether contraction-mediated glucose uptake is also affected. Rats
      were fed a diet rich in fat (FAT, 73% of energy) or carbohydrate (CHO, 66%) for 5
      wk. Hindquarters were perfused, and either glucose uptake or glucose transport
      capacity (uptake of 3-O-[14C]-methyl-D-glucose (40 mM)) was measured. Amounts of
      glucose transporter isoform GLUT-1 and GLUT-4 glucose-transporting proteins were
      determined by Western blot. Glucose uptake was lower (P < 0.05) in hindlegs from
      FAT than from CHO rats at submaximum and maximum insulin [4 +/- 0.4 vs. 5 +/- 0.3
      (SE) mumol.min-1.leg-1 at 150 microU/ml insulin] as well as during prolonged
      stimulation of the sciatic nerve (4.4 +/- 0.4 vs. 5.6 +/- 0.6 mumol.min-1.leg-1).
      Maximum glucose transport elicited by insulin (soleus: 1.7 +/- 0.2 vs. 2.6 +/-
      0.2 mumol.g-1.5 min-1, P < 0.05) or contractions (soleus: 1.8 +/- 0.2 vs. 2.6 +/-
      0.3, P < 0.05) in red muscle was decreased in parallel in FAT compared with CHO
      rats. GLUT-4 content was decreased by 13-29% (P < 0.05) in the various fiber
      types, whereas GLUT-1 content was identical in FAT compared with CHO rats. It is
      concluded that a FAT diet reduces both insulin and contraction stimulation of
      glucose uptake in muscle and that these effects are associated with diminished
      skeletal muscle glucose transport capacities and GLUT-4 contents.

PMID- 7573555
TI  - Effect of pregnancy on activation of central pathways following atrial
      distension.
AB  - Stimulation of the atrial volume receptors increases neural traffic to the
      ventrolateral medulla, which in turn sends output to, and receives input from,
      the lateral hypothalamic area. An integrated reflex and hormonal response is thus
      initiated. We wished to investigate first whether atrial distension results in
      activation of selected nuclei in the forebrain and, second, whether pregnancy
      modifies this response. Rats were implanted with indwelling intracardiac balloons
      positioned at the superior vena caval/right atrial junction. One week later, the
      balloons were inflated. The animals were then anesthetized, their brains fixed by
      perfusion, and the tissue prepared for visualization of c-fos activity. Atrial
      distension caused a significant increase in c-fos expression in the
      paraventricular nucleus, the medial preoptic area, and the lateral septum. This
      response was markedly attenuated in the pregnant animals. In conclusion, during
      pregnancy central pathways that are normally activated in responses to volume
      expansion, fail to respond to atrial distension. We propose that this allows
      blood volume to increase in the pregnant animal, without triggering homeostatic
      mechanisms.

PMID- 7573556
TI  - Thermal dehydration-induced thirst in rats: role of body temperature.
AB  - Male Sprague-Dawley rats were used to study the possible role of hyperthermia in
      the thirst associated with thermal dehydration. Rats were exposed to 40 degrees C
      for 4 h and then allowed access to water at different times after they were
      transferred to 25 degrees C. Delaying the time prior to allowing the rats to
      drink did not significantly alter either water intake or percent rehydration even
      though core temperature decreased during the first 1.5 h after removal from the
      heat. Exposing thermally dehydrated rats to 5 degrees C for 30 min prior to
      allowing them access to water also failed to significantly affect water intake or
      percent rehydration. Thermally dehydrated rats allowed to drink while remaining
      in the heat did not show a significant increase in water intake during the first
      hour or percent rehydration over rats drinking at 25 degrees C. Nondehydrated
      rats did show significant increases in water intake and percent rehydration when
      allowed to drink in the heat. Hyperthermia does not play a role in drinking in
      thermally dehydrated rats but can stimulate drinking in water-replete rats.

PMID- 7573557
TI  - Isolation, localization, and cardiovascular activity of tachykinins from the
      stomach of the bowfin Amia calva.
AB  - The bowfin is an extant representative of an ancient group of ray-finned fish
      with evolutionary connections to modern teleosts. A peptide with substance P-like
      immunoreactivity was isolated from an extract of bowfin stomach and its primary
      structure was established as Ser-Lys-Ser-His-Gln-Phe-Tyr-Gly-Leu-Met-NH2. This
      amino acid sequence resembles mammalian substance P only in the COOH-terminal
      region of the peptide. A second tachykinin with neurokinin A-like
      immunoreactivity isolated from the extract comprises 23 amino acid residues and
      shows limited structural similarity to mammalian neuropeptide-gamma. A randomly
      distributed population of cells in the gastric glands of the bowfin were
      immunostained with an antiserum raised against substance P, but no immunopositive
      structures were identified in the surface epithelium, lamina propria, or the
      nerve plexuses of the submucosa. Bolus injections of synthetic bowfin substance P
      (0.1-10 nmol/kg) into the bulbus arteriosus of unanesthetized bowfin resulted in
      a significant and dose-dependent rise in vascular resistance and arterial blood
      pressure (P < 0.01) and a fall in cardiac output (P < 0.05) without change in
      heart rate. After 5-10 min, arterial pressure and vascular resistance returned to
      preinjection levels, but cardiac output significantly (P < 0.05) increased over
      baseline values. The response to the peptide was unaffected by pretreatment of
      the animals with phentolamine. The study has shown that the stomach of the bowfin
      synthesizes tachykinins with novel structural features that display
      cardiovascular activity in this species.

PMID- 7573558
TI  - Sulfate/oxalate exchange by lobster hepatopancreatic basolateral membrane
      vesicles.
AB  - Purified basolateral membrane vesicles (BLMV) were prepared from lobster
      hepatopancreas by osmotic disruption and discontinuous sucrose gradient
      centrifugation. Radiolabeled sulfate uptake was stimulated by 10 mM
      intravesicular oxalate compared with gluconate-loaded vesicles. Sulfate/oxalate
      exchange was not affected by transmembrane valinomycin-induced potassium
      diffusion potentials (inside negative or inside positive), suggesting
      electroneutral anion transport. Sulfate uptake was not stimulated by the similar
      carboxylic anions formate, succinate, oxaloacetate, or ketoglutarate. Sulfate
      influx occurred by at least one saturable Michaelis-Menten carrier system
      [apparent Km = 6.0 +/- 1.7 mM; maximum flux (Jmax) = 382.3 +/- 37.0 pmol.mg
      protein-1 x 7 s-1]. Sulfate/oxalate exchange was significantly reduced by the
      anion antiport inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 4
      acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid but was not affected by
      bumetanide or furosemide. The possible physiological role of this exchange
      mechanism in anion/sulfate transport across the crustacean hepatopancreas is
      discussed.

PMID- 7573561
TI  - Na-D-glucose cotransport in renal brush-border membrane vesicles of an early
      teleost (Oncorhynchus mykiss).
AB  - Brush-border membrane vesicles (BBMV) enriched with alkaline phosphatase (8.1
      fold) and gamma-glutamyl transpeptidase (11.5-fold) were prepared from the
      rainbow trout kidney. D-[3H]glucose uptake was stimulated by inward Na gradients
      but not by K, choline, Li, N-methyl-D-glucamine, or mannitol gradients. Na
      dependent glucose uptake displayed overshoot in voltage-polarized vesicles (VPV;
      negative inside) but not in short-circuited vesicles (SCV). Recognition of
      carbons 2 and 3 of the glucopyranose ring was essential for glucose uptake.
      Phlorizin inhibited Na-dependent D-glucose uptake with an inhibition constant of
      11.4 microM. The Michaelis-Menten constant of glucose was 0.58 mM in VPV and
      increased to 1.49 mM in SCV, whereas that for sodium was 193 mM in VPV and
      similar in SCV. Maximum velocity of Na was reduced in SCV. The Hill coefficient
      was 1 for both Na and glucose in VPV and SCV. Our studies indicate a single Na-D
      glucose cotransporter that transports Na and glucose with a 1:1 stoichiometry and
      voltage-dependent kinetics. The transporter shares functional properties with
      both mammalian transporters SGLT1 and SGLT2.

PMID- 7573560
TI  - Sepsis-induced attenuation of glucagon and 8-BrcAMP modulation of the
      phosphoenolpyruvate carboxykinase gene.
AB  - Sepsis is associated with alterations in hepatic gluconeogenesis. We have
      previously demonstrated that this change is associated with reduced expression of
      the phosphoenolpyruvate carboxykinase (PEPCK) gene, despite an endogenous
      hormonal milieu that should favor increased expression of the gene. To further
      elucidate the mechanisms involved, we induced sepsis in fasted Sprague-Dawley
      rats via cecal ligation and single puncture, with sham-operated animals serving
      as controls, and we performed two sets of experiments. First, liver tissue was
      obtained from septic and sham-operated animals at 2, 6, 16, and 24 h after the
      induction of sepsis. Northern blot hybridization analysis revealed a progressive,
      sepsis-induced decrease in expression of PEPCK and an increase in the expression
      of beta-fibrinogen, an acute-phase reactant. In the second set of experiments, we
      tested whether this reduced expression resulted from an attenuated response to 1)
      glucagon and 2) 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). Twenty
      four hours after the induction of sepsis, the liver was isolated and perfused
      with either Krebs buffer with substrate only (unstimulated controls), Krebs
      buffer + substrate + 10(-8) M glucagon, or Krebs buffer + substrate + 10(-5) M 8
      BrcAMP. In sham-operated animals, perfusion with glucagon increased PEPCK mRNA
      levels and activity, whereas perfusion with buffer alone did not change mRNA
      levels and decreased activity. Glucagon perfusion of septic livers did not change
      either PEPCK mRNA levels or activity. Perfusion of sham-operated animals with 8
      BrcAMP increased PEPCK mRNA levels and activity, whereas perfusion with buffer
      alone resulted in a decrease in mRNA levels and activity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7573559
TI  - Endocrine consequences of prenatal sodium depletion prepare rats for high need
      free NaCl intake in adulthood.
AB  - Offspring of dams that were repeatedly sodium depleted during late pregnancy (at
      days E14, E17, and E20) expressed high need-free 3% NaCl intake in adulthood.
      Need-free 3% NaCl intake was greater in females, thereby respecting the sexual
      dimorphism of this behavior, and was increased further by successive sodium
      depletion in adulthood. Offspring from dams that had been sodium depleted while
      receiving the angiotensin-converting enzyme inhibitor, captopril, showed a need
      free NaCl intake similar to that of control rats nonneonatally sodium depleted.
      Trunk blood taken from dams at day E18, i.e., 24 h after the second treatment,
      revealed that sodium depletion produced marked increases in the dam's plasma
      angiotensin (ANG) II and aldosterone that were not present when dams were treated
      with captopril during sodium depletion, even though both groups displayed a
      similar hyponatremia. We therefore propose that, during prenatal sodium
      depletion, the activation of the angiotensin-aldosterone system rather than the
      loss of sodium itself is responsible for the modification in need-free NaCl
      intake behavior. Finally, we suggest that, during pregnancy, ANG II may have an
      organizational effect on the neural substrate in the fetal brain that subserves
      subsequent NaCl intake behavior.

PMID- 7573562
TI  - Cross fostering between normal and sodium-restricted rats: effects on peripheral
      gustatory function.
AB  - Rats restricted of dietary NaCl prenatally and thereafter exhibit abnormally low
      electrophysiological chorda tympani taste responses to sodium stimuli as adults.
      Recovery of responses can be induced by ingestion of NaCl, even at adulthood. To
      examine whether milk from sodium-replete mothers enables functional recovery in
      sodium-restricted rats, we recorded multifiber chorda tympani responses in adult
      animals that had been cross fostered during the suckling period. Sodium
      restricted animals cross fostered to control dams for postnatal weeks 1 and 2 did
      not recover normal sodium sensitivity. Surprisingly, control pups crossed to
      sodium-restricted mothers from postnatal days 1 to 14 showed an exaggerated
      response to NaCl as adults. These results indicate that milk from normal mothers
      ingested during postnatal weeks 1 and 2 is not sufficient to restore gustatory
      function in sodium-restricted rats. Importantly, it also appears that events
      occurring during the early suckling period of control rats determine long-term
      taste sensitivities to sodium.

PMID- 7573565
TI  - Arginine synthesis in enterocytes of neonatal pigs.
AB  - Arginine is deficient in porcine colostrum and milk, and yet the piglet has a
      particularly high requirement for this essential amino acid for rapid postnatal
      growth. To explain this paradox, arginine synthesis was quantified in enterocytes
      from newborn (0-day-old) and 2- to 7-day-old suckling pigs. Arginine was found to
      be synthesized from glutamine in 0- to 7-day-old pig enterocytes, but the rates
      of arginine synthesis were three- to fourfold greater in 0- to 2-day-old pigs
      than in 7-day-old pigs. To elucidate the developmental change of the intestinal
      arginine synthesis, the metabolism of glutamine to citrulline, the conversion of
      citrulline to arginine, and the activities of the enzymes involved were measured.
      The rates of metabolism of glutamine to citrulline were 2.5- to 3.5-fold greater
      in enterocytes from 0- to 2-day-old pigs than in cells from 7-day-old pigs, as
      were the rates of conversion of citrulline to arginine. The activities of all
      enzymes that synthesize arginine from glutamine, except pyrroline-5-carboxylate
      synthase and argininosuccinate lyase (ASL), increased in enterocytes from 2-day
      old pigs compared with 0-day-old pigs. The activities of all these enzymes
      decreased by approximately 75% in 7-day-old pigs compared with 2-day-old pigs.
      Arginase activity was negligible in enterocytes from 0- to 7-day-old pigs, thus
      minimizing intestinal hydrolysis of newly synthesized arginine and maximizing the
      endogenous provision of arginine. The results of this study demonstrate the
      presence of arginine-synthesizing enzymes and their developmental changes in
      postnatal pig enterocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573564
TI  - A single bout of exhaustive exercise affects integrated baroreflex function after
      16 days of head-down tilt.
AB  - We tested the hypothesis that one bout of maximal exercise performed 24 h before
      reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase
      integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated
      baroreflex function was assessed in seven subjects before and after two periods
      of HDT separated by 11 mo. On the last day of one HDT period, subjects performed
      a single bout of maximal cycle ergometry (exercise). Subjects did not exercise
      after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was
      evaluated using a neck collar device. Integrated baroreflex function was assessed
      by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva
      maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change
      in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM
      was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated
      vasoconstriction was assessed by measuring the late phase II rise in MAP.
      Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0
      ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8
      beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and
      phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated
      in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or
      exercise. The late phase II increase of MAP was 71% greater after exercise
      compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573563
TI  - Depressed expression of the inducible form of HSP 70 (HSP 72) in brain and heart
      after in vivo heat shock.
AB  - The heat shock gene expression plays a role in the protection of cells from
      injury. In the present study, we have analyzed the expression of heat shock
      protein (HSP) 72 (the major inducible form of the HSP 70 family) in different rat
      organs after a total body hyperthermia. The content of HSP 72 was greatest in
      liver and colon. In contrast, accumulation of HSP 72 was low in heart and brain
      (3-5% and < 1% of the amount in liver, respectively). This low expression of HSP
      72 in heart and brain could not be explained by a difference in the actual
      temperature within these organs. Analysis of cells in culture that resemble
      hepatocytes, myoblast, and neurons showed a pattern of HSP 72 expression similar
      to that observed in liver, heart, and brain in vivo after heat shock. These
      results suggest that this disparate expression of HSP 72 is due to intrinsic
      characteristics of the cell types rather than to physiological or environmental
      conditions. The differential expression of HSP 72 among different cell lines
      could be correlated with the different levels of protein synthesis protection.

PMID- 7573566
TI  - Dietary medium-chain triglycerides can prevent changes in myosin and SR due to
      CPT-1 inhibition by etomoxir.
AB  - To define determinants of subcellular structures of heart, Wistar-Kyoto rats
      (WKY) and spontaneously hypertensive rats (SHR) were treated for 5 wk with 15
      mg.kg-1.day-1 etomoxir [reduces mitochondrial carnitine palmitoyltransferase-1
      (CPT-1) activity and fatty acid synthesis]. To bypass CPT-1 inhibition, etomoxir
      treated rats were fed a medium-chain fatty acid (MCFA) diet. Etomoxir induced a
      proportionate growth of heart, which could partially (WKY, P < 0.05) or
      completely (SHR, P < 0.05) be prevented by the MCFA diet. Also the etomoxir
      induced increase in myosin V1 was partially prevented (P < 0.05). Etomoxir
      increased (P < 0.05) rate of sarcoplasmic reticulum (SR) Ca2+ uptake of WKY and
      SHR ventricular homogenates in the presence or absence of the SR Ca2+ release
      inhibitor ruthenium red. The MCFA diet resulted in SR Ca2+ uptake rates that were
      in between those of etomoxir-treated and untreated rats. The in vitro 32P
      incorporation into phospholamban and troponin I did not differ significantly in
      WKY. Etomoxir induced, however, an increase (P < 0.05) in the phosphorylated
      intermediate of the Ca2+ adenosinetriphosphatase in WKY that was prevented by the
      MCFA diet. In SHR, etomoxir increased the in vitro phospholamban phosphorylation,
      which was reduced compared with WKY. The data show that myosin and SR are
      affected by a chronically altered substrate utilization of heart.

PMID- 7573568
TI  - Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary
      tract of behaving rats.
AB  - The activity of single taste neurons was recorded from the nucleus of the
      solitary tract before (n = 41) and after (n = 58) awake, behaving rats were
      switched to a sodium-free diet. During sodium deprivation, the spontaneous
      activity of the neurons increased (142%), but responses to water and sapid
      stimuli decreased. For all neurons in the sample, the mean response to water
      decreased to 72% of its predeprivation level, NaCl dropped to 53%, sucrose to
      41%, citric acid to 68%, and quinine HCl to 84%. Despite the drop in magnitude,
      the response profiles of the taste neurons were not changed by the dietary
      condition. In the Na-replete state, 61% of the activity elicited by NaCl occurred
      in NaCl-best cells and 33% in sucrose-best neurons. In the depleted state, these
      values were 60 and 26%, respectively. Nevertheless, at the highest concentrations
      tested, deprivation did alter the relative responsiveness of the gustatory
      neurons to sucrose and NaCl in specific categories of neurons. Compared with
      acute preparations, dietary sodium deprivation in awake, behaving rats produced a
      more general reduction in the gustatory responses of neurons in the nucleus of
      the solitary tract. The largest reductions in elicited activity occurred for the
      "best stimulus" of a particular neuron, thus leading to smaller differences in
      response magnitude across stimuli, particularly at the highest concentrations
      tested.

PMID- 7573567
TI  - Quantity of sucrose alters the tissue pattern and time course of insulin
      resistance in young rats.
AB  - To determine the effects of the amount of sucrose in the diet on insulin
      stimulated glucose metabolism, euglycemic hyperinsulinemic clamps were performed
      on male Wistar rats after one of the following dietary treatments (n = 6
      8/treatment): 1) high-starch diet (68% of total energy) for 8 wk (ST8), 16 wk
      (ST16), or 30 wk (ST30); 2) high-sucrose diet (68% of total energy) for 8 wk
      (SU8), 16 wk (SU16), or 30 wk (SU30); or 3) low-sucrose diet (18% of total
      energy) for 8 wk (SUL8), 16 wk (SUL16), or 30 wk (SUL30). Body weights were
      similar in starch- and sucrose-fed rats at 8 wk (502 +/- 9 g), 16 wk (563 +/- 10
      g), and 30 wk (607 +/- 26 g). The glucose infusion rate (mumol.g-1.min-1)
      required to maintain similar glycemia during clamps was 73.1 +/- 8.8 in ST8, 29.7
      +/- 4.9 in SU8 (P < 0.05 vs. ST8 and SUL8), and 76.4 +/- 8.2 in SUL8; 69.9 +/-
      8.1 in ST16, 35.1 +/- 5.1 in SU16 (P < 0.05 vs. ST16 and SUL16), and 63.2 +/- 6.5
      in SUL16; and 65.4 +/- 7.7 in ST30, 26.0 +/- 5.3 (P < 0.05 vs. ST30), and 36.3 +/
      6.0 in SUL30 (P < 0.05 vs. ST30). Impaired suppression of hepatic glucose
      production accounted for 43, 39, and 34% of the decrease in the glucose infusion
      rate in SU8 compared with ST8, SU16 compared with ST16, and SU30 compared with
      ST30, respectively, but 78% in SUL30 compared with ST30. These results suggest
      that both high- and low-sucrose diets can produce insulin resistance in young
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573570
TI  - An intact glutamatergic trigeminal pathway is essential for the cardiac response
      to simulated diving.
AB  - Nasal water flow plus concomitant expiratory apnea in anesthetized (Innovar-Vet),
      paralyzed, and artificially ventilated rats produces immediate bradycardia. To
      investigate the origin of this response, four procedures were used to block the
      trigeminal pathway. 1) Trigeminal receptors within the nasal passages were
      anesthetized by infusing local anesthetic through the external nares. 2)
      Trigeminal nerves that innervate the nasal passages were sectioned bilaterally as
      they passed through the orbit. 3) The trigeminal neural pathway was blocked
      within the brain stem by either electrolytically lesioning or infusing local
      anesthetic into the spinal trigeminal nucleus interpolaris (Sp5I). 4) Synaptic
      transmission within Sp5I was prevented by infusing glutamate receptor antagonists
      D-2-amino-7-phosphonoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione. After
      each of the procedures was completed, the cardiovascular responses to nasal water
      flow plus apnea were either attenuated or eliminated. The major conclusion of
      this study is that an intact glutamatergic trigeminal pathway is required for
      manifestation of the cardiovascular responses to nasal stimulation. Evidence also
      suggests that N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors are
      both required for synaptic neurotransmission within Sp5I.

PMID- 7573571
TI  - Influence of the renal nerves on sodium excretion during progressive reductions
      in cardiac output.
AB  - The purpose of this study was to elucidate the role of the renal nerves in
      promoting sodium retention during chronic reductions in cardiac output. In five
      dogs, the left kidney was denervated and the urinary bladder was surgically
      divided to allow separate 24-h urine collection from the innervated and
      denervated kidneys. Additionally, progressive reductions in cardiac output were
      achieved by employing an externally adjustable occluder around the pulmonary
      artery and by servo-controlling right atrial pressure (control = 0.9 +/- 0.2
      mmHg) at 4.7 +/- 0.1, 7.5 +/- 0.1, and 9.8 +/- 0.2 mmHg for 3 days at each level.
      At the highest level of right atrial pressure, the 24-h values for mean arterial
      pressure (control = 97 +/- 3 mmHg) and cardiac output (control = 2,434 +/- 177
      ml/min) were reduced approximately 25 and 55%, respectively; glomerular
      filtration rate fell by approximately 35% and renal plasma flow by approximately
      65%. However, despite the sodium retention induced by these hemodynamic changes,
      there were no significant differences in renal hemodynamics or sodium excretion
      between the two kidneys during pulmonary artery constriction. In contrast, after
      release of the pulmonary artery occluder on day 9, sodium excretion increased
      more (approximately 28% during the initial 24 h) in innervated than in denervated
      kidneys. These results suggest that the renal nerves are relatively unimportant
      in promoting sodium retention in this model of low cardiac output but contribute
      significantly to the short-term elimination of sodium after partial restoration
      of cardiac output and mean arterial pressure.

PMID- 7573569
TI  - Intracerebroventricular injection of prostaglandin E2 increases splenic
      sympathetic nerve activity in rats.
AB  - The effects of central administration of prostaglandin E2 (PGE2) and its
      selective agonists on splenic sympathetic nerve activity (SNA) were investigated
      in urethan- and alpha-chloralose-anesthetized rats. An intra-third
      cerebroventricular (13V) injection of PGE2 (0.1-10 nmol/kg) increased splenic SNA
      in a dose-dependent manner. An I3V injection of an EP1 agonist, 17-phenyl-omega
      trinor PGE2 (1-30 nmol/kg), also resulted in a dose-dependent increase in splenic
      SNA, with a time course similar to that of PGE2-induced responses. In contrast,
      EP2 agonists, butaprost (10-100 nmol/kg I3V) and 11-deoxy-PGE1 (10-100 nmol/kg
      I3V), had no effect on splenic SNA. An I3V injection of M & B-28767 (an EP3/EP1
      agonist, EP3 >> EP1) increased splenic SNA only at high doses (10-100 nmol/kg).
      Pretreatment with an EP1 antagonist, SC-19220 (200 and 500 nmol/kg), completely
      blocked the responses of splenic SNA to PGE2 (0.1 nmol/kg) and M & B-28767 (10
      nmol/kg), respectively. These findings indicate that brain PGE2 increases splenic
      SNA through its action on EP1 receptors.

PMID- 7573572
TI  - Varying photoperiod in the laboratory rat: profound effect on 24-h sleep pattern
      but no effect on sleep homeostasis.
AB  - To assess the influence of the photoperiod on sleep regulation, laboratory rats
      were adapted to a long photoperiod (LPP; 16:8-h light-dark cycle, LD 16:8) or a
      short photoperiod (SPP; LD 8:16). The electroencephalogram (EEG) and cortical
      temperature (TCRT) were continuously recorded for a baseline day, a 24-h sleep
      deprivation (SD) period, and a recovery day. Data obtained previously for LD
      12:12 served for comparison. Whereas the photoperiod exerted a prominent effect
      on the 24-h sleep pattern, the 24-h baseline level of sleep and the response to
      SD were little affected. Recovery from SD was characterized by a marked rise in
      rapid eye movement sleep, a moderate rise in non-rapid eye movement sleep, and an
      initial enhancement of EEG slow-wave activity followed by a decrease below
      baseline. The amplitude and phase of the "unmasked" 24-h component of TCRT did
      not differ between LPP and SPP. Computer simulations demonstrated that the
      changes of TCRT and EEG slow-wave activity can be largely accounted for by the
      sequence of the vigilance states. We conclude that the photoperiod does not
      affect the basic processes underlying sleep regulation.

PMID- 7573573
TI  - Lack of relationship between opioid-induced changes in fetal breathing and plasma
      glucose levels.
AB  - The mechanisms by which opioids increase or decrease fetal breathing remain
      unclear. Fetal plasma glucose is known to modulate breathing activity, and
      opioids have been reported to alter glucose regulation in the adult. In this
      study, we investigated whether alterations in fetal breathing by opioids may be
      explained by changes in plasma glucose levels. We compared the effects of
      morphine (nonselective), [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu
      selective), and [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) on fetal
      breathing and plasma glucose in unanesthetized fetal sheep. Whereas morphine at
      1.2 and 5.0 mg/h iv resulted in an increase in breath number (P < 0.01), plasma
      glucose was decreased after 1.2 mg/h (P = 0.006) but increased after 5.0 mg/h (P
      = 0.008). DAMGO (100 micrograms/h icv) increased plasma glucose (P = 0.001) but
      reduced fetal breathing (P < 0.001). In contrast, DPDPE (30 micrograms/h icv)
      increased fetal breathing (P = 0.026) but had no effect on plasma glucose
      concentration. These data demonstrate that the actions of opioids on fetal
      glucose regulation and breathing are dependent on dose and receptor selectivity.
      However, there is no relationship between the effects of opioids on fetal
      breathing and plasma glucose concentration.

PMID- 7573574
TI  - Comparison of effects of adrenalectomy and RU-486 in rats given a choice of
      maintenance diet and fat supplement.
AB  - The effects of adrenalectomy (ADX) and the blockade of glucocorticoid receptors
      by RU-486 on Sprague-Dawley rats given a choice of a maintenance diet and a fat
      supplement were studied. Adult male rats were given free access to AIN-76A diet
      only (CON) or AIN-76A diet and a separate dietary fat option for 4 wk (FAT). They
      were then assigned to one of the following treatments: ADX, sham operation, ADX
      with corticosterone (CORT) replacement, RU-486 injections, or vehicle injections.
      Food intake and body weight were monitored daily for an additional 3 wk. ADX
      decreased caloric intake and weight gain in the FAT group more than in the CON
      group. RU-486 also decreased caloric and fat option intakes as well as weight
      gain. ADX, but not RU-486, reduced body fat content, lowered plasma insulin and
      triglyceride levels, and decreased glucose intolerance. CORT replacement
      partially prevented the effects of ADX on weight gain and body fat content. The
      results of this study indicate that ADX has greater effects on weight gain and
      body fat accumulation than does RU-486.

PMID- 7573575
TI  - Pregnancy enhances the pressor response to thromboxane analogues in rabbits.
AB  - In this study, we first tested the hypothesis that the previously demonstrated
      circulatory failure and thrombocytopenia induced by intracaval administration of
      thromboxane A2 (TxA2) analogues in nonpregnant (NP) rabbits [G. Losonczy, I.
      Mucha, J. DiPirro, J. Sweeney, G. Brown, J. Brentjens, and R. Venuto. Am. J.
      Physiol. 265 (Regulatory Integrative Comp. Physiol. 34): R772-R780, 1993] could
      be avoided if the compounds were given instead into the aortic arch. Conscious
      New Zealand White rabbits received bolus injections of U-46619 (5-20 micrograms)
      through a previously implanted catheter threaded into the aortic arch. Indeed,
      mean arterial pressure (MAP) rose modestly, and thrombocytopenia did not develop.
      Next, we compared the blood pressure responses of pregnant (P) rabbits with those
      of NP rabbits to intra-aortic U-46619 and I-BOP, because they had been found to
      be resistant to both the hypotensive and platelet aggregatory effects of
      intracaval U-46619. Resting blood pressure was lower in P than in NP rabbits (74
      +/- 3 vs. 95 +/- 2 mmHg), but showed a greater increase in response to U-46619.
      For example, following a 20-micrograms dose blood pressure rose 20 +/- 0.3 mmHg
      in P vs. 12 +/- 2.1 mmHg in NP rabbits (P < 0.02). Similar results were obtained
      with the second TxA2 analogue I-BOP. Pregnancy-induced enhancement of blood
      pressure elevation may be the consequence of peripheral vasoconstriction, which
      was not seen in NP rabbits. Thus the actions of TxA2 analogues U-46619 and I-BOP
      are markedly influenced by the route of administration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7573577
TI  - Why be concerned about recruitment?

PMID- 7573576
TI  - Angiotensin II and cardiovascular regulation in a freshwater teleost, Anguilla
      rostrata LeSueur.
AB  - Cardiac output (CO), dorsal aortic blood flow (BFDA) and blood pressure (PDA),
      and heart rate (HR) were recorded simultaneously in conscious freshwater eels.
      Physiological doses of [Asn1,Val5]angiotensin II (ANG II; 25-150 ng/kg iv) were
      used to investigate its effects on the blood flow [CO, BFDA, and estimated
      branchial shunting (BS)] and systemic vascular resistance (RSys) components of
      the pressor response and possible mechanism(s) of action. CO was increased mainly
      by an elevated stroke volume (SV) due to positive inotropy and/or Frank-Starling
      principle in a dose-related manner. An intact baroreceptor reflex attenuated the
      blood flow increase by 25% via the inhibitory cardiac vagal innervation. The
      elevation in estimated BS was a passive response to the increased CO, since the
      proportion of CO perfusing the pathway remained constant. PDA showed a similar
      dose-dependent increase in response to ANG II but the peak PDA preceded the peak
      CO responses at all doses; RSys was only transiently elevated at peak PDA. The
      increase in blood flow was an important contributor to the vasopressor responses.
      Alpha-Adrenergic blockade partially inhibited the pressor effect of ANG II (100
      ng/kg) primarily by attenuating the increase in blood flow (50-70%). The data
      provide evidence for an ANG II-mediated cardiovascular control in teleosts
      directly and indirectly via catecholamine release.

PMID- 7573578
TI  - Images in neuroscience. Neuroimaging, I.PET with [18F]fluorodeoxyglucose.

PMID- 7573579
TI  - Decline of U.S. medical student career choice of psychiatry and what to do about
      it.
AB  - OBJECTIVE: In 1994, only 3.2% of U.S. medical school graduates chose psychiatry,
      the lowest proportion since 1929. Success in recruiting such graduates is
      necessary to maintain adequate numbers of psychiatrists. The authors' goal was to
      gain an understanding of the determinants of specialty selection to ensure
      adequate recruitment. METHOD: They reviewed all recruitment-related English
      language publications since 1959: 173 papers, 17 reports, and 10 books. RESULTS:
      They found that recruitment has been cyclical, with success from 1940 to 1969 and
      from 1985 to 1988, decline from 1970 to 1984 and from 1989 to 1994, and a
      possible small upswing in 1995. The 1940-1969 success began with 1) public
      recognition of a dramatic shortage of psychiatrists to serve in the military and
      treat casualties and 2) the fervor of the community mental health movement, which
      promised to prevent mental illness; massive resources were provided for
      psychiatry during this period. The declines were associated with 1) the failure
      of the community mental health movement to fulfill its promise, 2) psychiatry's
      becoming more biologically oriented and medically conventional, and 3) the
      effects of managed care and increased competition for patients. The psychiatry
      departments that have high recruitment rates are in public-supported schools,
      particularly in the South, or give considerable priority and resources for
      medical student psychiatric education. CONCLUSIONS: A study of the psychiatric
      workforce is needed to ascertain whether there is a surplus or a shortage of
      psychiatrists. Regardless, to ensure adequate recruitment, medical institutions
      and departments of psychiatry must commit resources for student education in
      psychiatry.

PMID- 7573580
TI  - Progress toward achieving a common language in psychiatry, II: Results from the
      international field trials of the ICD-10 diagnostic criteria for research for
      mental and behavioral disorders.
AB  - OBJECTIVE: In preparing for the publication of ICD-10, the Division of Mental
      Health of the World Health Organization developed several versions of chapter V,
      which deals with mental and behavioral disorders. The version for research
      purposes is called the Diagnostic Criteria for Research (ICD-10 DCR) and gives
      operational criteria for the diagnosis of mental disorders. This article
      describes the results of international field trials undertaken to evaluate the
      draft criteria and refine them further. METHOD: Data were obtained to assess
      interrater agreement, the confidence with which diagnoses could be made, and the
      ease of use of the criteria. Additional substudies examined the concordance
      between ICD-10 DCR, ICD-10 Clinical Descriptions and Diagnostic Guidelines, and
      other national classification systems (e.g., DSM-IV). The field trials were
      carried out at 151 clinical centers in 32 countries by 942 clinician/researchers
      who conducted 11,491 individual assessments of patients. Results for cases
      assessed by at least two raters are reported here. RESULTS: Most
      clinician/researchers found the criteria to be explicit and easy to apply.
      Interrater agreement was high for most diagnostic categories. For some
      categories, such as those dealing with certain polymorphic psychotic disorders or
      milder forms of affective disorders, the criteria were rated as somewhat
      difficult to use, and reliability was lower. Comparison of the results of these
      field trials with those of the ICD-10 Clinical Descriptions and Diagnostic
      Guidelines demonstrated that there are increases in interrater agreement when the
      operational criteria are used. CONCLUSIONS: The use of internationally accepted
      research criteria enhances the reliability of diagnosis of mental disorders made
      in research settings worldwide.

PMID- 7573581
TI  - DSM-IV and the disappearance of agoraphobia without a history of panic disorder:
      new data on a controversial diagnosis.
AB  - OBJECTIVE: This analysis describes subjects who met rigorous criteria for DSM-III
      R agoraphobia without a history of panic disorder and makes inferences from these
      data regarding relationships among agoraphobia without a history of panic
      disorder, panic disorder, and panic disorder with agoraphobia. METHOD: Twenty-six
      subjects (seven men and 19 women) with agoraphobia without a history of panic
      disorder were identified from among 711 subjects recruited for a multicenter,
      longitudinal anxiety disorder study. Narrative transcripts prepared by raters
      from study evaluations were coded for limited symptom attacks, situational panic,
      catastrophic cognitions, and possible precipitants and stressors, course, and
      somatic and psychosocial treatments received. RESULTS: Sixty-five percent of the
      subjects reported experiences consistent with situational panic attacks, and 57%
      had definite or probable limited symptom attacks; these attacks usually preceded
      or appeared at the same time as avoidance behavior. Eighty-one percent had
      catastrophic cognitions associated with agoraphobia. Twenty-six percent reported
      a likely precipitating factor for symptom onset, and 30% reported a definite or
      probable major life stressor within 6 months before symptom onset. Cognitive
      behavioral treatments were relatively infrequently used. Course was relatively
      unchanged across the follow-up period. CONCLUSIONS: These data support a view of
      agoraphobia without a history of panic disorder on a continuum with uncomplicated
      panic disorder and with panic disorder and agoraphobia, rather than as a separate
      diagnosis.

PMID- 7573583
TI  - Negative symptoms in schizophrenia: a confirmatory factor analysis of competing
      models.
AB  - OBJECTIVE: The aim of the study was to examine different models of the factor
      structure of negative symptoms in schizophrenia through the use of a confirmatory
      factor analysis procedure. METHOD: The cohort comprised 253 inpatients diagnosed
      with schizophrenia according to DSM-III-R criteria. Negative symptoms were
      evaluated with the Scale for the Assessment of Negative Symptoms (SANS). Seven
      alternative models of negative symptoms were compared by means of confirmatory
      factor analysis. RESULTS: The unidimensional model fit the data modestly. More
      complex multifactorial models fit the data better than simpler models. Both five
      dimension models corresponding to the original SANS structure fit the data quite
      well; the model excluding inappropriate affect from the SANS was the best
      adjusted. CONCLUSIONS: Multidimensional models fit the data better than the
      unidimensional model. The data provide evidence for the factorial validity of the
      SANS and the characterization of the SANS subscales as true underlying dimensions
      of observable negative symptoms.

PMID- 7573582
TI  - D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum
      concentration: a PET study of schizophrenic patients.
AB  - OBJECTIVE: Central D1, D2, and 5-HT2 receptor occupancy in schizophrenic patients
      treated with clozapine was determined and related to clozapine serum
      concentrations. METHOD: Seventeen patients treated with clozapine (125-600
      mg/day) were examined with positron emission tomography (PET) and one to three of
      the following selective radioligands: [11C]SCH23390 (N = 11), [11C]raclopride (N
      = 16), and [11C]N-methylspiperone (N = 5). Clozapine concentration in serum was
      determined by gas chromatography/mass spectrometry. RESULTS: D2 receptor
      occupancy (20%-67%) was lower than that previously determined in patients treated
      with classical neuroleptics (70%-90%). D1 receptor occupancy (36%-59%) was higher
      than that induced by classical neuroleptics (0%-44%). 5-HT2 receptor occupancy
      was very high (84%-94%), even at low clozapine doses. Despite a 20-fold range in
      clozapine serum concentration (105-2121 ng/ml) at the time of PET examination, D2
      receptor occupancy was low in all patients and was not described by the
      curvilinear relationship between serum drug concentration and receptor occupancy
      that has been demonstrated for classical antipsychotics. CONCLUSIONS: The results
      confirm in an extended series of patients that clozapine is atypical with regard
      to degree of D2 receptor occupancy, a finding that may explain the lack of
      extrapyramidal side effects. The combination of relatively high D1, low D2, and
      very high 5-HT2 receptor occupancy values is unique to clozapine. Clozapine serum
      concentrations have not been unequivocally shown to predict clinical effects. In
      this study, concentration did not predict degree of occupancy in brain. Thus,
      careful clinical titration cannot be replaced by monitoring of drug
      concentrations for optimization of clozapine treatment in individual patients.

PMID- 7573584
TI  - Negative, psychoticism, and disorganized dimensions in patients with familial
      schizophrenia or bipolar disorder: continuity and discontinuity between the major
      psychoses.
AB  - OBJECTIVE: This study aimed to answer the following questions: 1) Can we reliably
      measure the psychopathologic dimensions of schizophrenia by using a lifetime
      frame and by rating acute and interepisode periods separately? 2) Can we
      reproduce in subjects with familial schizophrenia the characteristic three-factor
      structure of schizophrenic symptoms that has been found previously in general
      groups of schizophrenic patients? 3) Is the factor structure also present in
      familial bipolar disorder? METHOD: Lifetime measures of psychotic symptoms were
      taken through a slightly modified version of the Comprehensive Assessment of
      Symptoms and History for 138 patients with highly familial DSM-III-R
      schizophrenia (N = 51), bipolar disorder (N = 44), or spectrum disorders (N =
      43). Symptoms were rated separately in the acute episodes and in the stabilized
      interepisode intervals across the patients' lives. RESULTS: A satisfactory level
      of reliability was obtained. In this highly familial study group, the
      positive/negative factorial distinction was replicated, as was a three-factor
      model similar to that observed in prior general groups of schizophrenic patients.
      These factors were also present in bipolar affective disorder. The negative,
      psychoticism, and disorganized factor model applied more to the acute phase of
      illness than to the stabilized state. CONCLUSIONS: These findings offer an
      empirical basis for testing biological or genetic variables in relation to
      negative/positive symptom dimensions, rather than diagnoses. Observations of a
      shared structure for schizophrenia and bipolar disorder suggest some continuity
      in the causes of these disorders.

PMID- 7573585
TI  - Clinical effects of recent cocaine use on patients with acute schizophrenia.
AB  - OBJECTIVE: Dopamine function has been hypothesized to be involved in both
      producing schizophrenic symptoms and mediating cocaine's reinforcing properties.
      As a result, cocaine abuse in schizophrenic patients may be seen as a natural
      experiment that may alter the phenomenology and neurobiology of schizophrenia.
      This report concerns the clinical effects of cocaine abuse and cessation in
      schizophrenic patients at two times: when patients presented to the psychiatric
      emergency service and again after 4 weeks of hospitalization. METHOD: The
      subjects were 15 cocaine-abusing and 22 cocaine-abstaining schizophrenic
      patients. Diagnostic assessments were performed with the Structured Clinical
      Interview for DSM-III-R--Patient Version, which uses DSM-III-R criteria. All of
      the patients were assessed at both times with the Brief Psychiatric Rating Scale,
      the Scale for the Assessment of Positive Symptoms, and the Scale for the
      Assessment of Negative Symptoms. RESULTS: Cocaine-abusing schizophrenic patients
      showed fewer negative signs and more anxiety/depression at the hospital-admission
      assessment than their nonabusing counterparts. At retest, no group differences
      were detected in patients' negative signs or mood symptoms. Severity of positive
      symptoms was equal at both testing sessions. CONCLUSIONS: The significant
      difference in negative signs and mood symptoms at admission assessment was
      attributed to the neurobiological impact of cocaine. The role of psychostimulants
      in schizophrenic patients is discussed.

PMID- 7573587
TI  - Multicenter clinicopathological correlation in dementia.
AB  - OBJECTIVE: The aim of the present study was to determine the accuracy of clinical
      diagnoses of dementia in a large group of patients evaluated in a multicenter,
      university-based, Alzheimer's disease diagnostic and treatment program. METHOD:
      Clinical diagnoses and neuropathological results from seven collaborating
      Alzheimer's disease research centers were compared for 196 cases of dementia.
      RESULTS: When diagnoses of probable Alzheimer's disease, possible Alzheimer's
      disease, and Alzheimer's disease plus another condition were combined, 163 (83%)
      of the patients were clinically regarded as likely to have had Alzheimer's
      disease. Of those patients, 134 (82%) were found to have neuropathological
      changes diagnostic of Alzheimer's disease or Alzheimer's disease plus another
      condition. A total of 116 patients were diagnosed as having probable Alzheimer's
      disease; 100 (86%) of those were found to have pathological diagnoses of
      Alzheimer's disease or Alzheimer's disease plus another condition. Cerebral
      infarcts were found in 17% of the patients clinically diagnosed with probable
      Alzheimer's disease. Lewy bodies with variable Alzheimer's disease-type
      pathological changes were found in 7% of the patients with clinical diagnoses of
      probable Alzheimer's disease. Conversely, significant Alzheimer's disease-type
      pathological changes were found in 55% of the patients clinically diagnosed as
      having vascular dementia. CONCLUSIONS: Clinicians accurately predict Alzheimer's
      disease-type neuropathological findings in a high proportion of cases of dementia
      but may not predict cerebrovascular pathology and Lewy bodies in some patients
      with apparent clinical Alzheimer's disease and may often fail to predict
      Alzheimer's disease-type pathological findings in patients with apparent vascular
      dementia. With the emergence of effective treatments for Alzheimer's disease,
      there is an increasing need to optimize methods for ante-mortem diagnosis of
      dementia.

PMID- 7573586
TI  - SPECT findings on psychosis in Alzheimer's disease.
AB  - OBJECTIVE: This study examined whether psychosis in Alzheimer's disease is
      associated with cerebral perfusion patterns appreciable by single photon emission
      computed tomography (SPECT) scans. METHOD: All cooperative outpatients enrolled
      in an Alzheimer's disease research center with the diagnosis of probable
      Alzheimer's disease and a Clinical Dementia Rating of mild or moderate were
      interviewed with their primary caregivers. Current and past psychiatric
      functioning was assessed by using the Hamilton Depression Rating Scale, the
      Structured Clinical Interview for DSM-III-R, and the Behavioral Pathology in
      Alzheimer's Disease Rating Scale. Patients without premorbid psychosis received
      SPECT scans, and the scans of the patients with delusions or hallucinations (N =
      30) were compared to the scans of patients without these symptoms (N = 16).
      RESULTS: The patients with delusions (N = 29) had hypoperfusion of the left
      frontal lobe in relation to the right frontal lobe. The patients with
      hallucinations (N = 10) had hypoperfusion in the parietal lobe. CONCLUSIONS:
      Psychotic patients with Alzheimer's disease had a pattern of cerebral blood flow
      deficits significantly different from that of nonpsychotic patients. This
      suggests that patterns of cerebral dysfunction may be expressed symptomatically
      as psychosis.

PMID- 7573588
TI  - Prevalence of Alzheimer's disease and dementia in two communities: Nigerian
      Africans and African Americans.
AB  - OBJECTIVE: This article reports on a prevalence study of dementia and Alzheimer's
      disease among two groups of subjects with the same ethnic background but widely
      differing environments. METHOD: The study was conducted among residents aged 65
      years and older in two communities: Yorubas (N = 2,494) living in Ibadan,
      Nigeria, and African Americans (N = 2,212 in the community and N = 106 in nursing
      homes) living in Indianapolis, Indiana. The study design consisted of a screening
      stage followed by a clinical assessment stage for selected subjects on the basis
      of their performance on the screening tests. RESULTS: The age-adjusted prevalence
      rates of dementia (2.29%) and Alzheimer's disease (1.41%) in the Ibadan sample
      were significantly lower than those in the Indianapolis sample, both in the
      community-dwelling subjects alone (4.82% and 3.69%, respectively) and in the
      combined nursing home and community samples (8.24% and 6.24%, respectively). The
      prevalence rates of dementia and Alzheimer's disease increased consistently with
      advancing age in both study groups. CONCLUSIONS: To the authors' knowledge, this
      is the first study, using the same research method at the two sites, to report
      significant differences in rates of dementia and Alzheimer's disease in two
      different communities with similar ethnic origins.

PMID- 7573589
TI  - Psychiatric disorders and functional disability in outpatients with traumatic
      brain injuries.
AB  - OBJECTIVE: This study examined psychiatric sequelae of traumatic brain injuries
      in outpatients and their relation to functional disability. METHOD: Fifty
      consecutive outpatients with traumatic brain injuries who came to a brain injury
      rehabilitation clinic for initial evaluation were examined for DSM-III-R
      diagnoses with the use of the National Institute of Mental Health Diagnostic
      Interview Schedule. The patients completed the Medical Outcomes Study Health
      Survey to assess functional disability and a questionnaire to assess
      postconcussion symptoms and self-perceptions of the severity of their brain
      injuries and cognitive functioning. RESULTS: Thirteen (26%) of the patients had
      current major depression, and an additional 14 (28%) reported a first-onset major
      depressive episode after the injury that had resolved. Twelve (24%) had current
      generalized anxiety disorder, and four (8%) reported current substance abuse. The
      group with depression and/or anxiety was significantly more impaired than the
      nondepressed/nonanxious patients according to the Medical Outcomes Study Health
      Survey measures of emotional role functioning, mental health, and general health
      perceptions. The depressed/anxious group also rated their injuries as
      significantly more severe and their cognitive functioning as significantly worse,
      despite the lack of significant differences in objective measures of severity of
      injury and Mini-Mental State examination scores. The depressed patients reported
      significantly more postconcussion symptoms that were increasing in severity over
      time. CONCLUSIONS: Depression and anxiety are common in outpatients with
      traumatic brain injuries. Patients with depression or anxiety are more
      functionally disabled and perceive their injury and cognitive impairment as more
      severe. Depressed patients report more increasingly severe postconcussion
      symptoms.

PMID- 7573590
TI  - Early nonresponse to fluoxetine as a predictor of poor 8-week outcome.
AB  - OBJECTIVE: The purpose of this study was to quantify the proportion of patients
      who show no response to a fixed dose of fluoxetine after 2, 4, and 6 weeks of
      treatment and then respond by week 8. METHOD: In an open trial, 143 outpatients
      who met DSM-III-R criteria for major depressive disorder were treated with a
      regimen of fluoxetine, 20 mg/day. The authors analyzed the proportion of patients
      who had less than a 20% decrease from baseline in their scores on the Hamilton
      Rating Scale for Depression after 2, 4, and 6 weeks and who went on to have a 50%
      or greater reduction by week 8. A last-observation-carried-forward strategy was
      used to calculate conditional probabilities of 8-week response. Kaplan-Meier
      survival analysis was used to estimate probabilities of response at week 8 given
      degrees of response at week 2. RESULTS: Eighty-two subjects (57.3%) who started
      the trial responded by week 8. Of those subjects who showed no improvement at
      weeks 2, 4, and 6, the proportions of responders at week 8 were 36.4%, 18.9%, and
      6.5%, respectively. The Kaplan-Meier estimate of 8-week response given
      nonresponse at week 2 was 0.45. CONCLUSIONS: The proportion of patients with no
      response to antidepressant treatment by 4 or 6 weeks who responded by week 8 was
      substantially less than that for subjects who had at least a partial response.
      Nonresponse as early as week 2 predicted 8-week outcome.

PMID- 7573591
TI  - Individual psychotherapies for depressed HIV-positive patients.
AB  - OBJECTIVE: The authors present preliminary data from two treatment modalities of
      a randomized clinical trial in which they compared 16-week interventions of
      interpersonal psychotherapy to supportive psychotherapy. METHOD: HIV-positive
      patients who were not acutely medically ill and had scores of 15 or higher on the
      Hamilton Depression Rating Scale were randomly assigned to one of four treatment
      modalities. They were assessed by the Hamilton scale and Beck Depression
      Inventory at 8 and 16 weeks. Most subjects who underwent either interpersonal
      psychotherapy (N = 16) or supportive psychotherapy (N = 16) were male, gay or
      bisexual, white, and college educated. RESULTS: Results of last-observation
      carried-forward and completer analyses showed that scores on the Hamilton scale
      and Beck Depression Inventory decreased significantly for both treatments.
      Differential improvement for interpersonal psychotherapy appeared by midtreatment
      (week 8) and persisted at termination. CONCLUSIONS: This is the first controlled
      study of individual psychotherapies for depressed HIV-positive patients. Results
      suggest that a specific antidepressant psychotherapy, interpersonal
      psychotherapy, has advantages over a supportive therapy.

PMID- 7573592
TI  - Predictors of response to lithium in patients with psychoses.
AB  - OBJECTIVE: This study sought to characterize a subset of patients with DSM-III
      schizophrenia or schizophreniform disorder who respond to lithium. METHOD: Sixty
      six psychotic patients were given a systematic therapeutic trial of lithium
      alone. Differences in demographic characteristics, symptoms, and family history
      of psychotic disorders between the responders and nonresponders to lithium were
      explored. RESULTS: Responders and nonresponders did not differ significantly in
      age, duration of illness, length of current episode, distribution of RDC and DSM
      III diagnoses, or number of positive symptoms. However, the responders to lithium
      (N = 10) exhibited a paucity of negative symptoms and an absence of familial
      schizophrenic spectrum disorders. CONCLUSIONS: These preliminary results suggest
      the possibility of pretreatment identification of psychotic patients for whom
      neuroleptic medication could be avoided by therapeutic intervention with lithium
      alone.

PMID- 7573594
TI  - Auditory sensory ("echoic") memory dysfunction in schizophrenia.
AB  - OBJECTIVE: Studies of working memory dysfunction in schizophrenia have focused
      largely on prefrontal components. This study investigated the integrity of
      auditory sensory ("echoic") memory, a component that shows little dependence on
      prefrontal functioning. METHOD: Echoic memory was investigated in 20
      schizophrenic subjects and 20 age- and IQ-matched normal comparison subjects with
      the use of nondelayed and delayed tone matching. RESULTS: Schizophrenic subjects
      were markedly impaired in their ability to match two tones after an extremely
      brief delay between them (300 msec) but were unimpaired when there was no delay
      between tones. CONCLUSIONS: Working memory dysfunction in schizophrenia affects
      brain regions outside the prefrontal cortex as well as within.

PMID- 7573596
TI  - Diagnosis and serendipity.

PMID- 7573595
TI  - Use of prescription psychotropic drugs among suicide victims in New York City.
AB  - OBJECTIVE: The authors examined the rate of prescription psychotropic drug use
      among suicide victims at the time of their death. METHOD: From a total of 1,970
      suicides that occurred in New York City from 1990 to 1992, 1,635 cases that had a
      complete toxicologic analysis and an injury-death interval of 48 hours or less
      were assessed at autopsy for the presence of commonly prescribed antidepressants
      and neuroleptics. RESULTS: Prescription psychotropic medications were detected in
      only 16.4% (N = 268) of the suicide victims studied. Demographic factors
      associated with use of these drugs included female gender and white race.
      Poisoning accounted for 17.9% (N = 293) of all suicides studied, but
      antidepressants or neuroleptics were detected in less than half of these victims.
      Among all suicide victims in whom an antidepressant or neuroleptic was detected,
      almost half had used lethal methods other than poisoning. CONCLUSIONS: In this
      study, most individuals who committed suicide in New York City were not taking
      prescription psychotropic medications at the time of their death and either were
      not receiving pharmacotherapy or were noncompliant.

PMID- 7573597
TI  - Why is dissociative identity disorder infrequent in France?

PMID- 7573593
TI  - Selective serotonin reuptake inhibitor-induced sexual dysfunction: efficacy of a
      drug holiday.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether weekend drug
      holidays would improve sexual functioning in recovered depressed patients with
      selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. METHOD:
      Thirty outpatients who reported worsening of sexual functioning during SSRI
      treatment were instructed to discontinue their SSRIs after the Thursday morning
      dose and to restart the SSRIs (at their previous dosage) on Sunday at 12:00 noon
      for four weekends. RESULTS: Significant improvement in sexual functioning was
      reported by the patients taking sertraline and paroxetine but not by those taking
      fluoxetine. There were no statistically significant increases in mean Hamilton
      depression scores after discontinuation of the SSRIs; two patients had increases
      in scores from the 4-8 range to the 10-14 range. CONCLUSIONS: For some patients
      taking sertraline and paroxetine who experience sexual dysfunction side effects,
      brief drug holidays may allow for significant improvement in sexual functioning
      without a significant return of depressive symptoms.

PMID- 7573598
TI  - Sertraline for chronic obstructive pulmonary disease and comorbid anxiety and
      mood disorders.

PMID- 7573599
TI  - Olfactory function in winter seasonal affective disorder.

PMID- 7573601
TI  - Refusing lifesaving treatment.

PMID- 7573603
TI  - Validity of childhood abuse measurements.

PMID- 7573602
TI  - Validity of childhood abuse measurements.

PMID- 7573600
TI  - When is depression simply sadness?

PMID- 7573604
TI  - Complexities of research of abuse.

PMID- 7573605
TI  - Adolescent borderline personality disorder.

PMID- 7573606
TI  - Lithium or desipramine augmentation of fluoxetine treatment.

PMID- 7573607
TI  - Greater alcohol use in women with PMS.

PMID- 7573608
TI  - Differences in divergent thinking as a function of handedness and sex.
AB  - The relationship between handedness and divergent thinking was explored in four
      studies. Experiment 1 (N = 556) used the Alternate Uses Test, Experiment 2 (N =
      941) tested object synthesis, and Experiment 3 (N = 965) tested ideational
      flexibility. No difference as a function of handedness was found in Experiment 1,
      but in Experiments 2 and 3 divergent thinking was significantly related to
      handedness in males. Left-handed males had higher divergent thinking scores, and
      the scores rose systematically with increasing sinistrality. Handedness was not
      related to divergent thinking ability in females. Experiment 4 (N = 1,548) showed
      that these differences were not associated with superiority by left-handed
      individuals in convergent thinking. Interpretations based on altered neurological
      development due to factors such as fetal testosterone exposure are discussed.

PMID- 7573609
TI  - Selective influences of age and speed on associative memory.
AB  - Data from three studies involving a continuous paired associates task performed
      by adults of different ages were analyzed in an attempt to identify how
      processing speed might mediate age-related differences in associative memory. Age
      differences were found in measures postulated to represent encoding and
      consolidation processes, but not in a measure presumed to reflect rate of
      forgetting. It is suggested that increased age is associated with a reduction in
      the speed of executing processes concerned with establishing a stable internal
      representation, but not with an alteration in the rate at which encoded
      information is lost as a function of time or subsequent processing.

PMID- 7573610
TI  - Anger theory and management: a historical analysis.
AB  - Ancient and medieval views on anger--its desirability, causes, and control--are
      reviewed and compared with modern accounts. Although some differences emerge, for
      example with respect to women's anger, the modern accounts bear a marked
      resemblance to the older ones. There is also an early concern with the practice
      of anger management.

PMID- 7573611
TI  - Is carbon monoxide a risk factor for hospital admission for heart failure?

PMID- 7573612
TI  - Beyond population statistics.

PMID- 7573613
TI  - The inexcusable persistence of silicosis.

PMID- 7573614
TI  - Containing state health care expenditures--the competition vs regulation debate.

PMID- 7573615
TI  - Health systems' effects on health status--financing vs the organization of
      services.

PMID- 7573616
TI  - A short-term consumer agenda for health care reform.

PMID- 7573617
TI  - Health policy approaches to measuring and valuing human life: conceptual and
      ethical issues.
AB  - To achieve more cost-effective and equitable use of health resources, improved
      methods for defining disease burdens and for guiding resource allocations are
      needed by health care decision makers. Three approaches are discussed that use
      indicators that combine losses due to disability with losses due to premature
      mortality as a measure of disease burden. These indicators can also serve as
      outcome measures for health status in economic analyses. However, their use as
      tools for measuring and valuing human life raises important questions concerning
      the measurement of mortality and the multidimensions of morbidity; valuing of
      life, particularly regarding weighting productivity, dependency, age, and time
      preference factors; and conflicts between equity and efficiency that arise in
      allocation decisions. Further refinement of these tools is needed to (1)
      incorporate national and local values into weighting; (2) elaborate methods for
      disaggregating calculations to assess local disease patterns and intervention
      packages; and (3) develop guidelines for estimating marginal effects and costs of
      interventions. Of utmost importance are methods that ensure equity while
      achieving reasonable efficiency.

PMID- 7573619
TI  - Women at a sexually transmitted disease clinic who reported same-sex contact:
      their HIV seroprevalence and risk behaviors.
AB  - OBJECTIVES: This study compares characteristics, behaviors, and human
      immunodeficiency virus (HIV) infection in women who reported same-sex contact and
      women who had sex only with men. METHODS: Participants were patients attending a
      New York City sexually transmitted disease clinic. Structured questionnaires were
      administered by interviewers. RESULTS: Overall, 9% (135/1518) of women reported
      same-sex contact; among these, 93% also reported contact with men. Women
      reporting same-sex contact were more likely than exclusively heterosexual women
      to be HIV seropositive (17% vs 11%; odds ratio [OR] = 1.7, 95% confidence
      interval [CI] = 1.0, 2.6), to exchange sex for money/drugs (48% vs 12%, OR = 6.7,
      95% CI = 4.6, 9.8), to inject drugs (31% vs 7%, OR = 6.3, 95% CI = 4.1, 9.5), and
      to use crack cocaine (37% vs 15%, OR = 3.3, 95% CI = 2.2, 4.8). HIV in women
      reporting same-sex contact was associated with history of syphilis (OR = 8.8),
      sex for crack (OR = 5.7), and injection drug use (OR = 4.5). CONCLUSIONS: In this
      study, women who reported same-sex contact were predominantly bisexual. They had
      more HIV risk behaviors and were more often HIV seropositive than women who had
      sex only with men. Among these bisexual women, heterosexual contact and injection
      drug use were the most likely sources of HIV. There was no evidence of female-to
      female transmission.

PMID- 7573618
TI  - Ambient air pollution and hospitalization for congestive heart failure among
      elderly people in seven large US cities.
AB  - OBJECTIVES: Preexisting data sets were used to investigate the association
      between hospital admissions for congestive heart failure and air pollutants.
      METHODS: Medicare hospital admissions data, ambient air pollution monitoring
      data, and meteorological data were used to create daily values of hospital
      admissions for congestive heart failure, maximum hourly temperature, and maximum
      hourly levels of carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone.
      Data were compiled for each of seven cities (Chicago, Detroit, Houston, Los
      Angeles, Milwaukee, New York, and Philadelphia) for 1986 through 1989. Single
      pollutant and multipollutant models with adjustments for temperature, seasonal
      effects, and weekly cycles were used in conducting negative binomial regression
      analyses. RESULTS: Ambient carbon monoxide levels were positively associated with
      hospital admissions for congestive heart failure in the single-pollutant and
      multipollutant models for each of the seven cities. The relative risk of hospital
      admission for congestive heart failure associated with an increase of 10 ppm in
      carbon monoxide ranged from 1.10 in New York to 1.37 in Los Angeles. CONCLUSIONS:
      Hospital admissions for congestive heart failure exhibited a consistent
      association with daily variations in ambient carbon monoxide. This association
      was independent of season, temperature, and other major gaseous pollutants.

PMID- 7573620
TI  - Silicosis among gold miners: exposure--response analyses and risk assessment.
AB  - OBJECTIVES: This study sought to estimate the risk of silicosis by cumulative
      exposure-years in a cohort of miners exposed to silica, as well as the lifetime
      risk of silicosis under the current Occupational Safety and Health Administration
      (OSHA) standard (0.09 mg/m3). METHODS: In a cohort study of 3330 gold miners who
      worked at least 1 year underground from 1940 to 1965 (average 9 years) and were
      exposed to a median silica level of 0.05 mg/m3 (0.15 mg/m3 for those hired before
      1930), 170 cases of silicosis were determined from either death certificates or
      two cross-sectional radiographic surveys. RESULTS: The risk of silicosis was less
      than 1% with a cumulative exposure under 0.5 mg/m3-years, increasing to 68% to
      84% for the highest cumulative exposure category of more than 4 mg/m3-years.
      Cumulative exposure was the best predictor of disease, followed by duration of
      exposure and average exposure. After adjustment for competing risks of death, a
      45-year exposure under the current OSHA standard would lead to a lifetime risk of
      silicosis of 35% to 47%. CONCLUSIONS: Almost 2 million US workers are currently
      exposed to silica. Our results add to a small but increasing body of literature
      that suggests that the current OSHA silica exposure level is unacceptably high.

PMID- 7573621
TI  - Accounting for cluster randomization: a review of primary prevention trials, 1990
      through 1993.
AB  - OBJECTIVES: This methodological review aims to determine the extent to which
      design and analysis aspects of cluster randomization have been appropriately
      dealt with in reports of primary prevention trials. METHODS: All reports of
      primary prevention trials using cluster randomization that were published from
      1990 to 1993 in the American Journal of Public Health and Preventive Medicine
      were identified. Each article was examined to determine whether cluster
      randomization was taken into account in the design and statistical analysis.
      RESULTS: Of the 21 articles, only 4 (19%) included sample size calculations or
      discussions of power that allowed for clustering, while 12 (57%) took clustering
      into account in the statistical analysis. CONCLUSIONS: Design and analysis issues
      associated with cluster randomization are not recognized widely enough. Reports
      of cluster randomized trials should include sample size calculations and
      statistical analyses that take clustering into account, estimates of design
      effects to help others planning trials, and a table showing the baseline
      distribution of important characteristics by intervention group, including the
      number of clusters and average cluster size for each group.

PMID- 7573622
TI  - Health services access and use among older adults in North Carolina: urban vs
      rural residents.
AB  - OBJECTIVES: This study compared health service use and satisfaction with health
      care among older adults living in urban vs rural counties in North Carolina.
      METHODS: A stratified random sample of 4162 residents of one urban and four rural
      counties of North Carolina was surveyed to determine urban/rural variation in
      inpatient and outpatient health service use, continuity of care and satisfaction
      with care, and barriers (transportation, cost) to care. RESULTS: Inpatient and
      outpatient service use did not vary by residence in controlled analyses.
      Continuity of care was more frequent in rural counties. Transportation was not
      perceived as a barrier to health care more frequently in rural than in urban
      counties, but cost was a greater barrier to care among rural elderly people.
      CONCLUSIONS: In this sample, older persons living in rural counties within
      reasonable driving distance of urban counties with major medical centers used
      health services as frequently and were as satisfied with their health care as
      persons in urban counties. Cost of care, however, was a significant and
      persistent barrier among rural elderly people, despite Medicare coverage.

PMID- 7573623
TI  - State health care expenditures under competition and regulation, 1980 through
      1991.
AB  - OBJECTIVES: This paper examines health expenditure growth under two alternative
      policy approaches: competition-based managed care and state government rate
      regulation. METHODS: Data are presented on cumulative growth in real per capita
      health expenditures between 1980 and 1991 so as to compare California, a state
      with a pro-competitive policy, with the US average and with four states with
      established regulation programs. RESULTS: Real per capita expenditures for
      hospital services in the United States grew 54% between 1980 and 1991, while in
      California the growth was half the national rate, or 27%. Real per capita
      expenditures for physician services and drug expenditures in the United States
      grew by 82% and 65%, respectively, while in California these expenditures
      increased only 58% and 41%, respectively. California's growth rate was below that
      of all four regulatory states for all measures of health care cost inflation.
      CONCLUSIONS: On the basis of these findings, a properly structured competitive
      approach could play a significant role in controlling health expenditures in the
      United States.

PMID- 7573624
TI  - Health indicators and the organization of health care systems in western Europe.
AB  - OBJECTIVES: This study investigated the association between health care systems
      and health indicators in developed countries. METHODS: Cross-national comparisons
      were conducted with regression analysis between 17 Western European countries
      with two types of health care systems: national health services and social
      security systems. RESULTS: Health care expenditures were inversely correlated to
      potential years of life lost to females and to infant mortality rates; they were
      positively correlated to life expectancy for females. Regression models predicted
      that countries with national health services systems would have lower infant
      mortality rates at similar levels of gross domestic product (GDP) and health care
      expenditures. Finally, increases in health care expenditures would decrease the
      ratio of observed to predicted infant mortality rates according to GDP; this
      decrease would be greater in countries with national health services than in
      those with social security systems. The model predicted this difference to be
      about 13% at average levels of health expenditures. CONCLUSIONS: National health
      services seem to be more efficient at producing lower infant mortality rates than
      social security systems in Western European countries.

PMID- 7573626
TI  - Alberta's universal dental plan for the elderly: differences in use over 6 years
      by two cohorts.
AB  - OBJECTIVES: Dental services use by two cohorts under the universal dental plan
      for the elderly in Alberta, Canada, was examined. METHODS: Two birth cohorts 65
      to 69 years old at entry who used the plan from 1978 to 1979 (n = 17,816) or from
      1985 to 1986 (n = 27,474) were analyzed over 6 successive years for differences
      in dental services use and costs. RESULTS: The 1985/86 cohort received 24% more
      visits per patient than the 1978/79 cohort. Their inflation-adjusted expenditures
      increased by 19% mainly as a result of increases in denturists' expenditures
      (33%) (dentists' expenditures increased just 4% because of lower plan fee
      increases). The 1985/86 cohort received relatively many more periodontal and
      fewer denture services. Annual attendance over 6 consecutive years was high,
      especially for the 1985/86 cohort and dentists' patients; 55% of the 1985/86
      cohort who used dentists did so in 5 or all 6 years. CONCLUSIONS: Differences in
      plan expenditures per patient between the birth cohorts and dentists and
      denturists, along with the high continuity of care for dentists' patients, have
      important implications for planning and administering dental plans for the
      elderly. The large expenditure decreases for removable dentures and the large
      increases for periodontal services to the 1985/86 cohort are noteworthy.

PMID- 7573625
TI  - The challenge of defining and counting generalist physicians: an analysis of
      Physician Masterfile data.
AB  - OBJECTIVES: The study reviewed methods for measuring the specialty distribution
      of the US physician workforce. It was hypothesized that current databases and
      measurement conventions overestimate the number of generalist physicians.
      METHODS: A descriptive analysis of the American Medical Association (AMA)
      Physician Masterfile for California was done with different assumptions about the
      definition of generalists based on primary and secondary specialty information.
      RESULTS: A rigorous definition of generalist physician that excludes physicians
      with secondary practices in specialist fields resulted in an estimate of
      generalist physicians 25% lower than the number estimated by conventional
      workforce evaluation methods. Physicians who reported practicing in both
      generalist and specialist fields were more likely to be older, to be
      international medical school graduates, and to be in solo or duo practice
      compared with physicians who listed only generalist or specialist fields.
      CONCLUSIONS: The actual number of generalist physicians in the United States may
      be less than previously believed. Although the exact magnitude of the "hidden
      system" of specialists providing primary care is difficult to measure, at least a
      portion appear to already be counted as generalist physicians by current
      conventions.

PMID- 7573627
TI  - Increasing Medicaid child health screenings: the effectiveness of mailed
      pamphlets, phone calls, and home visits.
AB  - OBJECTIVES: A randomized controlled trial was conducted to test the effectiveness
      and cost effectiveness of three outreach interventions to promote well-child
      screening for children on Medicaid. METHODS: In rural North Carolina, a random
      sample of 2053 families with children due or overdue for screening was stratified
      according to the presence of a home phone. Families were randomly assigned to
      receive a mailed pamphlet and letter, a phone call, or a home visit outreach
      intervention, or the usual (control) method of informing at Medicaid intake.
      RESULTS: All interventions produced more screenings than the control method, but
      increases were significant only for families with phones. Among families with
      phones, a home visit was the most effective intervention but a phone call was the
      most cost-effective. However, absolute rates of effectiveness were low, and
      incremental costs per effect were high. CONCLUSIONS: Pamphlets, phone calls, and
      home visits by nurses were minimally effective for increasing well-child
      screenings. Alternate outreach methods are needed, especially for families
      without phones.

PMID- 7573628
TI  - Subclinical health effects in a population exposed to excess vitamin D in milk.
AB  - To evaluate subclinical health effects of excess vitamin D, a cross-sectional
      study was conducted of persons consuming milk from a dairy that had overfortified
      milk for at least 4 years. Milk consumption, sunlight exposure, medical symptoms,
      serum 25-hydroxyvitamin D (25[OH]D), serum and urinary calcium, and indicators of
      renal function were measured. Increased milk consumption was associated with
      increased serum 25(OH)D and urinary calcium. However, the prevalences of elevated
      serum 25(OH)D and calcium were no greater than expected, and data indicated
      normal renal function. It was concluded that most persons exposed to excess
      vitamin D exhibited no measurable adverse subclinical effects.

PMID- 7573629
TI  - Abortions in rural Idaho: physicians' attitudes and practices.
AB  - This study surveyed all family physicians, obstetrician-gynecologists, and
      general surgeons practicing in rural Idaho in 1994. Although most respondents
      provided a wide range of reproductive health services, less than 4% performed
      abortions, so most rural Idaho women wanting abortions must travel long distances
      for this procedure. Physicians report that they do not provide abortion services
      because of both their own moral objections and local community opposition to the
      procedure. Yet 26% of the respondents indicated interest in using RU-486 for
      abortions when it becomes available. This suggests that the development of
      acceptable medical abortifacients may improve access to this procedure even in
      very conservative rural areas.

PMID- 7573630
TI  - The effectiveness of alternative planned durations of residential drug abuse
      treatment.
AB  - Randomized controlled trials were conducted at two residential drug abuse
      treatment facilities to compare programs that differed in planned duration. One
      trial compared a 6-month and a 12-month therapeutic community program (n = 184),
      and the second compared a 3-month and a 6-month relapse prevention program (n =
      444). Retention rates over comparable time periods differed minimally by planned
      treatment duration, and the longer programs had lower completion rates. There was
      no effect in either trial of planned treatment duration on changes in
      psychosocial variables between admission and exit or on rates or patterns of drug
      use at follow-up between 2 and 6 months after exit.

PMID- 7573631
TI  - The quality of psychiatric emergency evaluations and patient outcomes in county
      hospitals.
AB  - Quality of care is widely assumed to be related to patient outcomes, but little
      is known about care in relation to outcomes in county general hospital
      psychiatric emergency services. It was hypothesized that conformity to
      professional standards (technical quality) and engagement of the patient (artful
      care) in psychiatric emergency services evaluations would contribute to improved
      patient functioning (Global Assessment Scale score) and appropriate disposition.
      A total of 583 cases in seven facilities were analyzed. Conformity to technical
      standards of care was associated with retention even after constraints, biases,
      and admission criteria had been taken into account. Conversely, artful care was
      associated with lower probability of retention and improved functioning.

PMID- 7573632
TI  - Treating early-stage breast cancer: hospital characteristics associated with
      breast-conserving surgery.
AB  - Despite growing acceptance of the fact that women with early-stage breast cancer
      have similar outcomes with lumpectomy plus radiation as with mastectomy, many
      studies have revealed the uneven adoption of such breast-conserving surgery.
      Discharge data from the Hospital Cost and Utilization Project, representing
      multiple payers, locations, and hospital types, demonstrate increasing trends in
      breast-conserving surgery as a proportion of breast cancer surgeries from 1981 to
      1987. Women with axillary node involvement were less likely to have a lumpectomy,
      even though consensus recommendations do not preclude this form of treatment when
      local metastases are present. Non-White race, urban hospital location, and
      hospital teaching were associated with an increased likelihood of having breast
      conserving surgery.

PMID- 7573633
TI  - Attitudes toward genetic testing for colon cancer risk.
AB  - This study examined public interest regarding genetic testing for colon cancer
      susceptibility. Survey data were collected from 383 adults in Utah. Respondents
      were very (47.3%) or somewhat (36.6%) interested in taking this genetic test.
      Nearly 95% reported that they would share their results with others. Individuals
      with higher income and with a perceived risk of getting colon cancer were the
      most interested in testing. Individuals without health insurance and widowed
      individuals were the least likely to share their test results. If respondents
      were told that they carried a gene for colon cancer, most would be concerned with
      how to reduce their risk of getting the disease.

PMID- 7573635
TI  - Encouraging mammography use among underserved women through a celebration of
      breast health.

PMID- 7573636
TI  - A communitywide needle/syringe disposal program.

PMID- 7573634
TI  - Rationing health care and the need for credible scarcity: why Americans can't say
      no.
AB  - With adequate cost containment unlikely in the foreseeable future, health care
      use will have to be curtailed, ideally with open and explicit criteria for
      equitably allocating resources or rationing. Yet, consensus on any such criteria
      appears remote because Americans cannot say no to health care. Americans may
      refuse to accept rationing for two reasons. The absence of any global limitation
      on health care resources may encourage patients to believe that health care
      resources are not scarce and do not need to be rationed. A belief in vitalism-
      that everyone is morally entitled to unlimited longevity and good health--may
      discourage setting limits on one's own care. Together, these characteristics may
      foster the belief that denials of health care services, especially by health
      insurers, are arbitrary or unfair refusals to pay for existing resources and not
      a necessary method of rationing scarce resources. If this hypothesis is true,
      Americans are unlikely to achieve consensus on any equitable allocation of health
      care unless they face an actual shortage (credible scarcity) of health care
      resources that makes it necessary to ration care.

PMID- 7573637
TI  - Integrating indicators into a public health quality improvement system.

PMID- 7573638
TI  - Promoting healthy eating: Contra Costa County's food policy.

PMID- 7573639
TI  - Smoking cessation counseling during routine public prenatal care.

PMID- 7573640
TI  - Back pain and risk of suicide among Finnish farmers.

PMID- 7573641
TI  - Prevalence, promotion, and person: the 3 Ps of firearm use.

PMID- 7573642
TI  - The origins of health standards for quartz exposure.

PMID- 7573643
TI  - Job auction.

PMID- 7573644
TI  - The treatment of acute combined ruptures of the anterior cruciate and medial
      ligaments of the knee.
AB  - We performed a prospective study of 46 patients with ruptures of the anterior
      cruciate ligament and medial ligamentous structures. All patients had anterior
      cruciate ligament allograft reconstructions. Group I comprised 34 patients in
      whom all of the medial structures were ruptured (parallel and oblique fibers of
      the superficial medial collateral ligament and the posteromedial capsule) and
      were treated operatively. In Group II (12 patients), the superficial medial
      ligament fibers only were ruptured and these were treated nonoperatively. All
      patients started an immediate motion and rehabilitation program. Forty-four
      patients returned for followup at a mean of 5.3 years (range, 2 to 8.9)
      postoperatively. The results were assessed using the Cincinnati Knee Rating
      System. At followup, 20 knees (59%) in Group I and 9 knees (73%) in Group II had
      less than 3 mm of increased displacement on KT-1000 arthrometer testing (134 N).
      The overall rate of anterior cruciate ligament graft failure was 15%: six (18%)
      in Group I and one (8%) in Group II. No patient had more than 2 mm of increase on
      valgus stress testing at 5 degrees or 25 degrees of knee flexion. The overall
      ratings were as follows: Group I, 20 knees (58%) excellent or good and 14 knees
      (42%) fair or poor; and Group II, 11 knees (91%) excellent or good and one knee
      (9%) fair. Knee motion complications and patellofemoral symptoms were common in
      the patients rated fair or poor in Group I.

PMID- 7573645
TI  - Achilles tendon ruptures. A new method of repair, early range of motion, and
      functional rehabilitation.
AB  - We prospectively treated 29 athletes who had Achilles tendon ruptures according
      to a functional rehabilitation protocol. The 25 male and 4 female patients had a
      mean age of 35 years (range, 19 to 56). The repair was performed with a Krackow
      suture of No. 2 nonabsorbable polyfilament. Patients began range-of-motion
      exercises 72 hours after surgery, used a posterior splint for 2 weeks, and then
      began ambulation in a hinged orthosis. Six weeks after surgery, use of the
      orthosis was discontinued, full weightbearing was allowed, and progressive
      resistance exercises were initiated. Isokinetic strength and endurance testing
      were performed at 3, 6, and 12 months after surgery. There were no reruptures.
      Two patients developed superficial wound infections that responded to debridement
      or local wound care. One patient suffered a pulmonary embolism. At 3 months'
      followup, isokinetic testing showed the mean functional deficits were 36% and 35%
      of the opposite leg at 60 and 120 deg/sec, respectively. By 6 months, the mean
      deficits were 2.9% and 2.3% at 60 and 120 deg/sec, respectively. All patients
      returned to preinjury activity levels at a mean of 4 months (range, 3 to 7) after
      repair. By 12 months, there were no significant differences in ankle motion,
      isokinetic strength, or endurance as compared with the uninvolved side.

PMID- 7573646
TI  - Arthroscopic assessment of the medial collateral ligament complex of the elbow.
AB  - The extent that the medial collateral ligament complex could be visualized by
      arthroscopy was determined in 10 fresh cadaveric elbows from 10 individuals. We
      carefully exposed the medial collateral ligament complex through a muscle
      splitting incision before performing arthroscopy. The anterior and posterior
      bundles were identified and marked by placing 4.0 nylon sutures deep to the
      bundles to aid in arthroscopic visualization. A portion of the anterior bundle
      was visible in only one elbow and in that elbow only the most anterior 25% of the
      anterior bundle was seen. Attempts to visualize the anterior bundle through
      additional portals were unsuccessful. Varying the flexion angle of the cadaveric
      elbow from 0 degrees to 130 degrees also failed to improve visualization.
      Conversely, the entire posterior bundle, including humeral and ulnar insertion
      sites, could be seen in all 10 specimens using the posterior portals. We also
      noted that direct pressure was placed on the ulnar nerve in all specimens when
      the arthroscope or any arthroscopic instrument was advanced into the
      posteromedial gutter in contact with the posterior bundle because of its
      proximity immediately adjacent to the ulnar nerve. The inability to reliably see
      the anterior bundle and the humeral or ulnar insertion sites of this ligament may
      limit the value of the arthroscope when assessing medial collateral ligament
      injuries. Additionally, great care should be taken when using the arthroscope or
      other instruments in the posteromedial gutter because the ulnar nerve lies
      immediately adjacent to the thin posterior bundle and capsule.

PMID- 7573647
TI  - Open versus closed chain kinetic exercises after anterior cruciate ligament
      reconstruction. A prospective randomized study.
AB  - We conducted a prospective, randomized study of open and closed kinetic chain
      exercises during accelerated rehabilitation after anterior cruciate ligament
      reconstruction to determine if closed kinetic chain exercises are safe and if
      they offer any advantages over conventional rehabilitation. The closed kinetic
      chain group used a length of elastic tubing, the Sport Cord, to perform
      weightbearing exercises and the open kinetic chain group used conventional
      physical therapy equipment. Results are reported with a minimum 1-year followup
      (mean, 19 months). Pre- and postoperative evaluation included the Lysholm knee
      function scoring scale, Tegner activity rating scale and KT-1000 arthrometer
      measurements. Overall, stability was restored in over 90% of the knees.
      Preoperative patellofemoral pain was reduced significantly; 95% of the patients
      had a full range of motion. The closed kinetic chain group had lower mean KT-1000
      arthrometer side-to-side differences, less patellofemoral pain, was generally
      more satisfied with the end result, and more often thought they returned to
      normal daily activities and sports sooner than expected. We concluded that closed
      kinetic chain exercises are safe and effective and offer some important
      advantages over open kinetic chain exercises. As a result of this study, we now
      use the closed kinetic chain protocol exclusively after anterior cruciate
      ligament reconstruction.

PMID- 7573648
TI  - Outcome of elbow surgery in professional baseball players.
AB  - We reviewed the records of 72 professional baseball players who underwent
      arthroscopic or open elbow surgery. The most common diagnoses were posteromedial
      olecranon osteophyte (65%), ulnar collateral ligament injury (25%), and ulnar
      neuritis (15%). Intraarticular loose bodies were found in 39% of the patients.
      Fifty-nine patients (82%) were observed for a minimum of 24 months, with an
      average of 42 months' followup. Forty-seven players (80%) returned to play for a
      minimum of one season (73% at the same or higher level of play), and 17% of the
      players retired initially because of their elbow injury. One third of the players
      required two or more surgical procedures, with 25% of these patients requiring an
      ulnar collateral ligament reconstruction after removal of a posteromedial
      olecranon osteophyte. The patients with posteromedial olecranon osteophytes had
      the highest rate of reoperation, and patients who underwent ulnar collateral
      ligament reconstruction had a higher rate of return to play. The incidence of
      ulnar collateral ligament injuries was most likely underestimated in this group
      of athletes, with initial treatment directed at the secondary injuries instead of
      the primary ulnar collateral ligament injury.

PMID- 7573649
TI  - Prolonged reaction time in patients with chronic lateral instability of the
      ankle.
AB  - Impaired proprioception has been suggested as one cause of chronic lateral
      instability of the ankle. We subjected 15 ankles in 13 patients with symptoms of
      chronic lateral instability to sudden angular displacement. The reaction times in
      the peroneus longus and the tibialis anterior muscles were recorded and compared
      with those from 15 control ankles. Significantly longer ipsilateral reaction time
      was recorded in the patients (65 ms) compared with the controls (49 ms). We
      concluded that delayed proprioceptive response to sudden angular displacement of
      the ankle may predispose an individual to or be a cause of chronic lateral
      instability of the ankle.

PMID- 7573650
TI  - Basketball shoe height and the maximal muscular resistance to applied ankle
      inversion and eversion moments.
AB  - To determine if the height of a basketball shoe alters the maximal inversion and
      eversion moment that can be actively resisted by the ankle in the frontal plane,
      we tested 20 healthy, young adult men with no recent ankle injuries. Subjects
      underwent unipedal functional ankle strength testing under weightbearing
      conditions at 0 degrees, 16 degrees, and 32 degrees of ankle plantar flexion
      using a specially designed testing apparatus. Testing was performed with the
      subject wearing either a low- or a three quarter-top basketball shoe. Shoe height
      did not significantly affect an individual's ability to actively resist an
      eversion moment at any angle of ankle plantar flexion. However, tests at 0
      degrees of ankle plantar flexion demonstrated that the three quarter-top
      basketball shoe we tested significantly increased the maximal resistance to an
      inversion moment by 29.4%. At 16 degrees of ankle plantar flexion, inversion
      resistance was also significantly improved by 20.4%. These results show that
      athletic shoe height can significantly increase the active resistance to an
      inversion moment in moderate ankle plantar flexion. The findings apply to a
      neutral foot position in the frontal plane, an orientation equivalent to the
      early phase of a potential ankle sprain.

PMID- 7573651
TI  - The effect of femoral tunnel position and graft tensioning technique on posterior
      laxity of the posterior cruciate ligament-reconstructed knee.
AB  - We report the effects of femoral tunnel position and graft tensioning technique
      on posterior laxity of the posterior cruciate ligament-reconstructed knee. An
      isometric femoral tunnel site was located using a specially designed alignment
      jig. Additional femoral tunnel positions were located 5 mm proximal and distal to
      the isometric femoral tunnel. With the graft in the proximal femoral tunnel,
      graft tension decreased as the knee flexed; with the graft in the distal femoral
      tunnel, graft tension increased as the knee flexed. When the graft was placed in
      the isometric femoral tunnel, a nearly isometric graft tension was maintained
      between 0 degrees and 90 degrees of knee flexion. One technique tested was
      tensioning the graft at 90 degrees of knee flexion while applying an anterior
      drawer force of 156 N to the tibia. This technique restored statistically normal
      posterior stability to the posterior cruciate ligament-deficient knee between 0
      degrees and 90 degrees for the distal femoral tunnel position, between 0 degrees
      and 75 degrees for the isometric tunnel position, and between 0 degrees and 45
      degrees for the proximal tunnel position. When the graft was tensioned with the
      knee in full extension and without the application of an anterior drawer force,
      posterior translation of the reconstructed knee was significantly different from
      that of the intact knee between 15 degrees and 90 degrees for all femoral tunnel
      positions.

PMID- 7573652
TI  - The effect of drilling and soft tissue grafting across open growth plates. A
      histologic study.
AB  - We examined the ability of a soft tissue graft to inhibit the formation of a bony
      bridge within tunnels drilled across open femoral and tibial growth plates in a
      canine model. A fascia lata autograft was placed in tunnels drilled across the
      distal femoral and proximal tibial physes in four skeletally immature dogs. Four
      additional dogs had a similar procedure performed, but the drill holes were left
      empty. The growth plates were evaluated at either 2 weeks or 4 months
      postoperatively using high-resolution radiography and routine histologic study. A
      bony bridge spanned the growth plate in all nongrafted animals as early as 2
      weeks postoperatively. However, the fascia lata autograft prevented bone
      formation within the tunnels of all grafted animals, which maintained normal
      growth plate anatomy throughout the length of the study. The results of this
      study demonstrate that a soft tissue graft of fascia lata placed in drill holes
      across open growth plates will prevent the formation of a bony bridge. These
      findings provide basic science support to those clinical studies that report no
      apparent alteration in growth plate function after the use of intraarticular
      techniques to reconstruct the anterior cruciate ligament in children and
      adolescents.

PMID- 7573654
TI  - Lateral traction during shoulder arthroscopy: its effect on tissue perfusion
      measured by pulse oximetry.
AB  - We studied the effect of three methods of shoulder traction during arthroscopy on
      arterial oxygen saturation measured by a pulse oximeter applied to the fingertip
      of the arm in traction. Simple longitudinal traction ablated the oxygen
      saturation in only 1 of 30 patients. Adding vertical traction perpendicular to
      the arm ablated the oxygen saturation in 25 of 30 patients when a 2-inch wide
      sling was used and in 7 of 30 patients when a 4-inch sling was used. In this
      series, the pulse oximeter did not demonstrate gradual gradations in arterial
      oxygen saturation loss. Rather, the pulse oximeter provided an all-or-none
      warning signal for tissue hypoxia.

PMID- 7573655
TI  - Results of arthroscopic debridement of glenoid labral tears.
AB  - We studied the long-term results of a prospectively selected group of 24 patients
      with 12 anteroinferior and 12 posterior glenoid labral lesions; all patients had
      functional instability but none had ligamentous detachment. After arthroscopic
      debridement, patients involved in throwing sports were not allowed to return to
      full athletic activity until full strength of the external rotators was achieved
      and documented on isokinetic evaluation. Followup was 36 to 72 months with an
      average of 48 months. Follow-up isokinetic evaluation revealed an average +4.4%
      and +8.6% concentric strength and -4.3% and -0.4% eccentric strength of the
      operated shoulder compared with the uninvolved shoulder at 90 and 180 deg/sec,
      respectively. Long-term good or excellent results were achieved in 21 patients,
      and 16 were functioning at their preinjury level of sports activities. Sixty-two
      percent of baseball pitchers were unimpaired in pitching. The average University
      of California Los Angeles shoulder rating score was 31 of 35 (11 excellent, 10
      good, and 3 poor) and the average Rowe-Zarins ratings scale was 85 of 100 (8
      excellent, 13 good, and 3 poor). These results justify an initial arthroscopic
      debridement of anteroinferior or posterior labral flap tears rather than
      capsulorrhaphy when there is no gross instability or Bankart lesion.

PMID- 7573653
TI  - The role of the cruciate and posterolateral ligaments in stability of the knee. A
      biomechanical study.
AB  - The role of the posterolateral and cruciate ligaments in restraining knee motion
      was studied in 11 human cadaveric knees. The posterolateral ligaments sectioned
      included the lateral collateral and arcuate ligaments, the popliteofibular
      ligament, and the popliteal tendon attachment to the tibia. Combined sectioning
      of the anterior cruciate and posterolateral ligaments resulted in maximal
      increases in primary anterior and posterior translations at 30 degrees of knee
      flexion. Primary varus, primary internal, and coupled external rotation also
      increased and were maximal at 30 degrees of knee flexion. Combined sectioning of
      the posterior cruciate and posterolateral ligaments resulted in increased primary
      posterior translation, primary varus and external rotation, and coupled external
      rotation at all angles of knee flexion. Examination of the knee at 30 degrees and
      90 degrees of knee flexion can discriminate between combined posterior cruciate
      ligament and posterolateral injury and isolated posterolateral injury. The
      standard external rotation test performed at 30 degrees of knee flexion may not
      be routinely reliable for detecting combined anterior cruciate and posterolateral
      ligament injury. However, measurements of primary anterior-posterior translation,
      primary varus rotation, and coupled external rotation may be used to detect
      combined anterior cruciate and posterolateral ligament injury.

PMID- 7573656
TI  - Biomechanical assessment of the healing response of the rabbit patellar tendon
      after removal of its central third.
AB  - The objective of this study was to determine the biomechanical properties of the
      healing patellar tendon after removal of its central third. This was accomplished
      by removing the central third of the patellar tendon from the right limb of 30
      mature New Zealand White rabbits. The tendon of the contralateral normal limb
      served as the unoperated control. The rabbits were separated into five test
      groups according to healing time: time of surgery and 1, 2, 3, and 6 months after
      surgery. The ultimate failure strength of the patellar tendons with the central
      third removed was significantly less than the failure strength of the
      contralateral normal patellar tendons at all time intervals after surgery. At the
      time of surgery, the ultimate failure strength values of the operated patellar
      tendons were on average 53% of the normal patellar tendons, increasing to 72% of
      normal at 6 months. There was a significant correlation between the ultimate
      failure strength of the operated tendons and healing time. The positive slope for
      this regression indicated that the ultimate failure strength of the operated
      tendons converged toward normal as healing progressed. Failure mode of the
      operated tendon did not depend on healing time.

PMID- 7573657
TI  - Injuries in Junior A ice hockey. A three-year prospective study.
AB  - This 3-year prospective cohort observational analysis of elite amateur hockey
      players ranging in age from 17 to 20 years on a United States Hockey League team
      describes ice hockey injuries using a strict definition of injury, standardized
      reporting strategies, and diagnosis by a team physician. One hundred forty-two
      injuries were recorded for an on-ice injury rate of 9.4 per 1000 player hours. A
      player was 25 times more likely to be injured in a game (96.1 per 1000 player
      game hours) than in practice (3.9 per 1000 player-practice hours). Game-related
      injuries were more frequent in the third period, and practice-related injuries
      occurred more often in the first third of the season. Collisions represented 51%
      of the total injuries. The most common types of injuries were strains,
      lacerations, contusions, and sprains. The face and the shoulder were most
      frequently injured. A facial laceration was the most common injury;
      acromioclavicular joint sprain was the second most common injury. Facial
      lacerations typically occurred in games and were stick related. Further research
      is necessary to determine if injuries in Junior A amateur ice hockey can be
      reduced by mandatory full facial protection, enforcement of existing rules,
      improvement in shoulder pad design, and by focusing more attention on stretching
      programs.

PMID- 7573658
TI  - Radiation exposure during fluoroarthroscopically assisted anterior cruciate
      reconstruction.
AB  - We prospectively evaluated the radiation exposure during 50 consecutive
      fluoroscopically assisted anterior cruciate ligament reconstructions. Three
      different methods of anterior cruciate ligament reconstruction were performed
      using either rolled fascia lata allograft or bone-tendon-bone autograft. For the
      50 procedures, total time using the fluoroscope was 119.61 minutes, or 2.38
      minutes per procedure. The 16 primary fascia lata allograft reconstructions
      averaged 1.38 minutes of fluoroscope use per procedure compared with 4.69 minutes
      for the two revision allograft fascia lata surgeries, 3.14 minutes per procedure
      for the 30 primary bone-tendon-bone reconstructions, and 4.18 minutes per
      procedure for the two surgeries performed with an allograft meniscal transplant.
      The difference in exposure time between the 16 primary allograft fascia lata
      surgeries and the 30 primary allograft or autograft bone-tendon-bone surgeries
      was statistically significant. The average radiation exposure to the surgeon was
      0.67 mrem per minute of fluoroscope use. It would take 7463.08 minutes of
      fluoroscope time, or 11,139 primary fascia lata allograft reconstructions, to
      exceed the recommended occupational exposure limit of 5000 mrem per year. It
      appears that the orthopaedic surgeon receives minimal radiation when using the
      fluoroscope to assist in anterior cruciate ligament reconstruction, especially
      when doing a primary fascia lata allograft procedure.

PMID- 7573659
TI  - Patellar taping: a radiographic examination of the medial glide technique.
AB  - The purpose of this study was to radiographically determine the effectiveness of
      the McConnell medial glide patellar taping technique. Twenty apparently healthy
      men, between ages 18 and 35, participated in this study. Subjects underwent a
      series of three radiographs in a modified Merchant view. First, a bilateral
      tangential view of the patellofemoral joints was taken to establish a baseline.
      Next, the same view was obtained with the experimental knees taped using the
      McConnell medial glide technique. Subjects then underwent a standardized exercise
      protocol to stress the tape and the accompanying knee structures. This was
      followed by a third view of the patellofemoral joints. Radiographs were measured
      using the Merchant congruence angle and analyzed statistically with dependent,
      mean difference tests. Results from this study indicate that the McConnell medial
      glide technique was effective in significantly moving the patella medially (P =
      0.003), but that the tape was ineffective in maintaining this significance after
      exercise (P < 0.001). In 3 subjects (15%) of this sample, the tape was
      ineffective in moving the patella medially in any degree. One interesting finding
      was that exercise caused a statistically significant (P = 0.016) lateral shift
      from baseline in the control knees. This may suggest some clinical significance
      for patellar taping in preventing excessive lateral shift.

PMID- 7573660
TI  - Tibial stress reaction in runners. Correlation of clinical symptoms and
      scintigraphy with a new magnetic resonance imaging grading system.
AB  - Medial tibial pain in runners has traditionally been diagnosed as either a shin
      splint syndrome or as a stress fracture. Our work using magnetic resonance
      imaging suggests that a progression of injury can be identified, starting with
      periosteal edema, then progressive marrow involvement, and ultimately frank
      cortical stress fracture. Fourteen runners, with a total of 18 symptomatic legs,
      were evaluated and, within 10 days, referred for radiographs, a technetium bone
      scan, and a magnetic resonance imaging scan. In 14 of the 18 symptomatic legs,
      magnetic resonance imaging findings correlated with an established technetium
      bone scan grading system and more precisely defined the anatomic location and
      extent of injury. We identified clinical symptoms, such as pain with daily
      ambulation and physical examination findings, including localized tibial
      tenderness and pain with direct or indirect percussion, that correlated with more
      severe tibial stress injuries. When clinically warranted, we recommend magnetic
      resonance imaging over bone scan for grading of tibial stress lesions in runners.
      Magnetic resonance imaging is more accurate in correlating the degree of bone
      involvement with clinical symptoms, allowing for more accurate recommendations
      for rehabilitation and return to impact activity. Additional advantages of
      magnetic resonance imaging include lack of exposure to ionizing radiation and
      significantly less imaging time than three-phase bone scintigraphy.

PMID- 7573661
TI  - The effect of nonablative laser energy on joint capsular properties. An in vitro
      mechanical study using a rabbit model.
AB  - To evaluate the effect of laser energy at nonablative levels on the mechanical
      properties of joint capsular tissues, we tested the femoropatellar joint capsules
      of 12 mature New Zealand White rabbits. Specimens were divided into three
      treatment groups (5, 10, and 15 watts) and one control group. All specimens were
      first nondestructively mechanically tested to determine stiffness and
      viscoelastic properties and then treated with laser energy or served as a
      control. Shrinkage was recorded and mechanical testing was repeated. The
      application of laser energy resulted in 9%, 26%, and 38% reduction in capsular
      tissue length for the 5, 10, and 15 watt groups, respectively. Tissue shrinkage
      was significantly and strongly correlated with energy density. Laser energy
      caused a significant decrease in tensile stiffness only in the 10 and 15 watt
      groups. Laser energy did not change the relaxation properties at any energy
      density. This study demonstrates that significant capsular shrinkage can be
      achieved with the application of nonablative laser energy without detrimental
      effects to the viscoelastic properties of the tissue; although at higher energy
      densities, laser energy did lessen capsular stiffness properties. The results of
      this study should be interpreted with caution until in vivo studies are
      performed.

PMID- 7573662
TI  - Anterior cruciate ligament graft tensioning in full extension.
AB  - The purpose of this study was to determine anterior laxity and graft forces in
      cadaveric knees after anterior cruciate ligament reconstruction in which the
      graft is tensioned with the knee in full extension. We also analyzed the clinical
      results from a series of patients who had ligament reconstructions using this
      technique. We performed anterior cruciate ligament reconstructions on seven fresh
      cadaveric knees and then measured the anterior laxity, graft set force, and graft
      tension. We also did a prospective minimum 2-year followup on 57 patients who
      underwent anterior cruciate ligament reconstruction. The in vitro data showed
      average anterior laxity of 1.1 mm greater than the intact knee with an 89-N
      anterior force at 30 degrees of knee flexion. Average graft set force was 68 N,
      and graft tension in extension was 18 N. In the clinical portion of the study,
      knee laxity improved from 7.5 to 0.8 mm (side-to-side difference at 89 N). The
      patients' Lysholm and Tegner scores improved from 65 to 90 and 3.9 to 5.6,
      respectively. Only one patient had a postoperative contracture. The results of
      this study suggest that graft tensioning in full extension provides a low
      incidence of flexion deformity, maintaining excellent functional results and
      satisfactory biomechanics.

PMID- 7573664
TI  - Incomplete, intrasubstance strain injuries of the rectus femoris muscle.
AB  - Rectus femoris muscle strain injuries commonly occur at the distal muscle-tendon
      junction of the quadriceps tendon. However, we have recently recognized a pattern
      of strain injury that consists of an incomplete intrasubstance tear at the muscle
      tendon junction formed by the deep tendon of the muscle's indirect head and those
      muscle fibers originating from this tendon. These injuries are found more
      proximally within the thigh than the "classic" distal rectus femoris muscle
      strain. We reviewed 10 athletes with these intrasubstance tears, all of whom had
      diagnostic imaging performed using computed tomography or magnetic resonance
      imaging or both. Two of these patients required surgical intervention. The
      mechanism of injury usually involved kicking or sprinting. All patients had
      chronic thigh pain or an anterior thigh mass or both. Physical examination
      revealed thigh asymmetry and a nontender to mildly tender intrasubstance muscle
      mass. Magnetic resonance imaging demonstrated abnormal signal intensity centered
      about the intramuscular tendon of the indirect head of the muscle. Surgical
      findings included a mass of fibrous scar and fatty tissue encasing the deep
      tendon. Surgical removal of this fibrous mass appears curative. We contrast this
      injury from distal strains of the rectus femoris muscle, as well as from soft
      tissue neoplasms.

PMID- 7573663
TI  - An explanation for various rectus femoris strain injuries using previously
      undescribed muscle architecture.
AB  - We performed cadaveric dissection of the rectus femoris muscle to correlate the
      various lesions of strain injury seen with imaging studies to the muscular
      anatomy. The proximal tendon is composed of a superficial, anterior portion from
      the direct head, and a deep intramuscular portion from the indirect head. The
      muscle fibers arising from the anterior superficial tendon of the direct head
      travel in a posterior and distal direction to insert on the posterior tendon of
      insertion, giving the proximal muscle a unipennate architecture. Muscle fibers
      from the intramuscular tendon of the indirect head originate on both the medial
      and lateral sides of the tendon and insert on the distal posterior tendon to
      create its bipennate structure. Three chronic strain injuries involving the
      midmuscle belly substance were explored grossly and microscopically. It appears
      that one type of acute strain injury occurs in the midmuscle belly with
      disruption of the muscle-tendon junction of the intramuscular tendon resulting in
      local hemorrhage and edema. More chronically, this hematoma organizes into a
      fatty, loose connective tissue encasement of the deep intramuscular proximal
      tendon. Serous fluid from the hematoma may remain within the connective tissue
      sheath, creating a pseudocyst with the deep intramuscular tendon of the indirect
      head at its center. The muscle's anatomy helps to explain a different rectus
      femoris strain injury.

PMID- 7573665
TI  - Lumbar transverse process fractures in professional football players.
AB  - In the general population, fractures of the transverse processes of lumbar
      vertebrae occur in cases of high-energy blunt trauma, often in motor vehicle
      accidents. Football players may incur the same fractures, but the circumstances
      and outcomes are different in this specific subgroup. A review of 29 cases among
      National Football League players reveals that associated visceral injuries are
      rare, and the time lost from sports is only an average of 3.5 weeks.

PMID- 7573666
TI  - Human immunodeficiency virus (HIV) and other blood-borne pathogens in sports.
      Joint position statement. The American Medical Society for Sports Medicine
      (AMSSM) and the American Academy of Sports Medicine (AASM).

PMID- 7573667
TI  - An electromyographic analysis of the knee during functional activities.

PMID- 7573668
TI  - Partial tears of the anterior cruciate ligament. Are they clinically detectable?

PMID- 7573669
TI  - Metanephric adenoma. Clinicopathological study of fifty patients.
AB  - We report 50 examples of an uncommon type of renal adenoma from the files of the
      Armed Forces Institute of Pathology. They appear to be benign tumors with no
      malignant potential, and their chief importance is related to the fact that they
      are most often misinterpreted as renal cell carcinoma or epithelial Wilms' tumor.
      They predominated in females by well over 2:1. The mean age of the patients was
      41 years, with a range of 5 to 83 years, and the mean size was 5.5 cm, with a
      range of 0.3 to 15.0 cm. Presenting signs and symptoms included pain in 11,
      hematuria in five, and palpable mass in five. In 20 patients the tumors were
      found incidentally during evaluation for other problems, and in six the other
      problem was polycythemia. This finding establishes a higher incidence of
      polycythemia in renal adenoma than in other previously reported renal diseases.
      Also of preoperative importance is the fact that these tumors are more commonly
      calcified than other renal neoplasms. Microscopically, these tumors consist of
      very small epithelial cells that form very small acini in an acellular stroma.
      Less often, they form tubular, glomeruloid, or polypoid and papillary formations.
      Most also show evidence of regression in the form of scarring and calcification.
      These lesions seem histogenetically related to epithelial Wilms' tumor, and, in
      fact, the two may occur together. They are histologically very similar to the
      metanephric hamartomatous element of nephroblastomatosis.

PMID- 7573670
TI  - The MIC2 antibody 013. Practical application for the study of thymic epithelial
      tumors.
AB  - The lymphocytes that accompany thymomas express an immature T-cell phenotype, as
      usually demonstrated by CD1 or TdT immunoreactivity. Even when thymomas
      metastasize or occur in ectopic sites, the infiltrating T lymphocytes show this
      unique immature phenotype, contrasting with thymic and nonthymic carcinomas, in
      which the infiltrating T lymphocytes typically show a mature phenotype (CD1 and
      TdT negative). Therefore, the presence of an immature T-cell population in an
      epithelial tumor strongly supports a diagnosis of thymoma. The availability of an
      antibody that consistently marks immature T-cells in routine paraffin sections
      would be of great help in the study of thymic tumors. In this report, we describe
      the use of MIC2 antibody (013), which has been widely used for the diagnosis of
      Ewing's sarcomas and peripheral primitive neuroectodermal tumors because it
      intensely stains thymocytes. Immunohistochemical staining was performed on
      paraffin sections of normal/hyperplastic thymus (18 cases), thymoma (62 cases),
      thymic carcinoma (nine cases), tumors showing borderline features between thymoma
      and thymic carcinoma (three cases), and ectopic hamartomatous thymoma (two
      cases). T-cell and B-cell antibodies were also applied to aid in the
      interpretation. In the normal thymus, almost all lymphocytes in the cortex
      stained with 013, whereas fewer than 5% of those in the medulla were 013
      positive. In thymomas, including the three ectopic thymomas and the single case
      of metastatic thymoma, most lymphocytes were 013 positive, except the spindle
      cell foci (medullary thymoma or medullary component of mixed thymoma), in which
      the percentage of 013-positive lymphocytes was lower (5-30%). Within the pale
      foci of "medullary differentiation" and the perivascular spaces of lymphocyte
      rich thymomas, few lymphocytes showed 013 positivity, indicating that the T
      lymphocytes in these areas were more mature. None of the thymic carcinomas
      harbored 013-positive lymphocytes. Among the three cases of borderline
      thymoma/thymic carcinoma, only one harbored 013-positive lymphocytes. The 013
      positive lymphocytes were not seen in the ectopic hamartomatous thymomas. In
      normal lymph nodes and nonthymic carcinomas studied as controls, there were no or
      at most small numbers of isolated 013-positive lymphocytes. We conclude that
      interpreted in the proper context, MIC2 antibody can serve as a useful marker of
      immature T-cells and thus help in the confirmation of a diagnosis of thymoma in
      small biopsy specimens, ectopic thymoma, or metastatic thymoma; in the
      distinction between invasive thymoma and thymic carcinoma; and in the
      classification of thymomas.

PMID- 7573672
TI  - Transitional cell neoplasms (carcinomas and inverted papillomas) of the uterine
      cervix. A report of five cases.
AB  - We report five transitional cell neoplasms of the uterine cervix: three
      infiltrating high-grade transitional cell carcinomas and two inverted
      transitional cell papillomas. The patients with TCCs were aged 34, 73, and 81
      years, two presented with vaginal bleeding and the third with a large cystic
      ovarian mass. The three transitional cell carcinomas had a superficial
      noninvasive papillary component. Two tumors metastasized, one to the pelvic lymph
      nodes, the other to the ovary. The two patients with metastasis are alive after
      radical hysterectomy or total abdominal hysterectomy and chemotherapy, but follow
      up is short. The third patient is currently receiving radiotherapy.
      Microscopically, the transitional cell carcinomas were similar to those
      originating in the urinary bladder or ovary. The inverted transitional cell
      papillomas were discovered in the cervixes of young adult women, one of whom had
      atypical squamous cells on a cervical smear at her presentation. The second
      patient had a slightly raised lesion in the cervix noted when routine smears were
      obtained. The microscopic features of the inverted transitional cell papillomas
      were similar to those of the corresponding tumor of the urinary bladder. It is
      important to separate transitional cell carcinomas from other papillary cancers
      of the cervix to delineate their clinical and pathological features and establish
      the prognostic differences, if any, from squamous cell carcinoma. Inverted
      transitional cell papilloma of the cervix represents a hitherto undescribed
      benign neoplasm arising at this site. These cases illustrate that cervical
      epithelium, which is known to undergo benign transitional cell metaplasia, may
      also give rise to benign and malignant transitional cell neoplasms.

PMID- 7573671
TI  - Localized and diffuse mesotheliomas of the genital tract and peritoneum in women.
      A clinicopathologic study of nineteen true mesothelial neoplasms, other than
      adenomatoid tumors, multicystic mesotheliomas, and localized fibrous tumors.
AB  - Peritoneal mesotheliomas are rare in women, compared to serous epithelial
      neoplasms with which they are often confused. We evaluated the clinicopathologic
      features of 19 true mesothelial neoplasms affecting the genital tract or
      peritoneum of women (other than adenomatoid tumors, benign multicystic
      mesotheliomas, and localized fibrous tumors) to characterize their
      clinicopathologic features and to determine their clinical behavior. Six tumors
      were localized to one anatomic site at presentation, and 13 involved more than
      one anatomic site. The six localized tumors were solitary, small (0.8-2.0 cm),
      polypoid or nodular lesions, five of which were incidental findings. All had a
      predominantly tubulopapillary pattern, either pure or mixed with adenomatoid-like
      or small solid foci. Nuclear grade ranged from 0 to 2. Mitotic figures (MF) were
      absent in two tumors. The mitosis count in the other four tumors was < 1 MF/10
      high-power microscopic fields (HPF) (average method) and ranged from 1 to 3 MF/10
      HPF (highest count method). Five patients were alive without recurrence after
      postoperative intervals ranging from 19 months to 9 years (median, 5 years); one
      patient died of metastatic gastric carcinoma at 14 months. Thirteen tumors
      involved more than one anatomic site and were classified as diffuse mesothelioma.
      Typically, these tumors were symptomatic and accompanied by ascites. The tumors
      had either a plaque-like or endophytic configuration. Eleven were purely
      epithelial mesotheliomas, and two had a minor sarcomatoid component.
      Tubulopapillary patterns were present in 10 tumors, usually admixed with focal
      adenomatoid-like or solid patterns, and three had a purely solid pattern. All 13
      tumors had grade 3 nuclei. The mitosis count ranged from < 1 to 2 MF/10 HPF
      (average count method) with a range of 1-4 MF/10 HPF by the highest count method.
      Immunohistochemically, 13/13 tumors stained for cytokeratin (AE1/AE3). None were
      immunoreactive for polyclonal carcinoembryonic antigen (CEA), Leu-M1, or B72.3.
      One diffuse mesothelioma stained focally for Ber-EP4, and electron microscopy
      confirmed the mesothelial nature of this tumor. Nine patients died of tumor after
      postoperative intervals ranging from 1 month to 6 years. Eleven patients had
      received postoperative adjuvant intraperitoneal or systemic chemotherapy. One
      patient died with increased abdominal girth 8 years after operation and one
      course of intraperitoneal chemotherapy, though the role of mesothelioma in her
      death was uncertain. One patient was alive with diffuse tumor and persistent
      ascites 25 months after six courses of intraperitoneal chemotherapy. One patient
      was alive without evidence of disease 4 months after two courses of systemic
      chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7573673
TI  - Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma.
      A clinicopathological study of 13 cases.
AB  - The recognition and classification of the different varieties of splenic low
      grade B-cell lymphomas have been hampered by the rarity of histological studies
      of surgical splenectomy specimens of B-cell lymphoma. In an effort to
      characterize the recently described splenic marginal zone lymphoma (SMZL), we
      conducted a survey of 13 patients with this type of tumor using the criteria
      defined by Schmid for its recognition (Schmid et al., Am J Surg Pathol
      1992;16:455-66). Primary splenic high-grade lymphomas, T-cell lymphomas, and
      secondary infiltration by other recognized low-grade B-cell lymphomas, with the
      exception of splenic lymphoma with villous lymphocytes, were excluded. This
      selection gave rise to a homogeneous group of tumors with similar clinical,
      histological, immunohistochemical, and molecular features. Our study showed the
      critical parameters for their recognition to be morphological, including
      macroscopic micronodularity and the constant presence of white- and red-pulp
      infiltration, marginal zone pattern, and plasmacytic differentiation. No t(14;18)
      or PRAD-1/cyclin D1 overexpression was detect able in any case. Clinically, the
      tumors were widespread with a protracted evolution. Nodal infiltration by SMZL in
      our cases was morphologically similar to monocytoid B-cell lymphoma. SMZL could
      constitute the largest group of primary splenic malignant lymphomas, partially
      overlapping with splenic lymphoma with villous lymphocytes. Specific molecular
      markers for SMZL have yet to be defined. Because of the limited number of cases,
      the question of therapy for this group of lymphomas must remain open for the
      future.

PMID- 7573674
TI  - Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases,
      including four with a malignant spindle cell component.
AB  - Eight mesonephric adenocarcinomas of the uterine cervix, four of which had a
      malignant spindle-cell component, occurred in women aged 34 to 71 (median 43,
      mean 54.5) years, bringing to 14 the number of cervical mesonephric carcinomas in
      the literature. The tumors with a malignant spindle-cell component ("malignant
      mesonephric mixed tumors") are, with one possible exception, the first reported
      examples at this site. The patients, almost all of whom presented with vaginal
      bleeding, underwent hysterectomy; five also had a pelvic lymph node dissection.
      The tumors were all stage IB, although microscopic lymph node metastases were
      found in two cases. Gross examination revealed an invasive cervical mass in each
      case. On microscopic examination, seven tumors were adjacent to mesonephric
      hyperplasia, which in five cases was florid and focally atypical; in the
      remaining case, occasional non-neoplastic mesonephric tubules were found only
      within the tumor. The adenocarcinomas typically exhibited a variety of patterns,
      including a ductal pattern resembling endometrioid adenocarcinoma, a small
      tubular pattern, a retiform pattern, a solid pattern, and a sex-cord-like
      pattern. These disparate patterns frequently caused diagnostic difficulty. The
      spindle-cell component generally resembled endometrial stromal sarcoma or a
      nonspecific spindle-cell sarcoma; one tumor also contained multiple foci of
      osteosarcoma and another, a single chondroid focus. Immunohistochemical staining
      for a variety of antigens failed to reveal a distinctive profile, although all
      the carcinomas were immunoreactive for vimentin. Follow-up in six cases revealed
      three patients to be alive without evidence of recurrence at postoperative
      intervals of 2 to 3 years. Recurrent tumor developed in a fourth patient 1 year
      after hysterectomy; she was treated with chemotherapy and was alive and free of
      disease at 2 years. Another patient had intra-abdominal recurrences (including
      liver metastases) at 9 and 11 years and was alive with tumor at 13 years. Death
      at 8.5 months in a final patient was probably due to an independent stage IIc
      ovarian clear-cell carcinoma. These and prior observations in the literature
      suggest that malignant mesonephric tumors of the cervix may be more indolent than
      their mullerian counterparts, from which they should be distinguished.
      Mesonephric carcinomas in this site should also be distinguished from florid
      mesonephric hyperplasia, with which they are usually associated.

PMID- 7573676
TI  - Hepatic adenoma in the pediatric age group. Clinicopathological observations and
      assessment of cell proliferative activity.
AB  - The clinicopathological findings of eight children with hepatic adenoma in the
      absence of cirrhosis are presented. The lesions ranged in diameter from 0.1 to
      14.5 cm. Associated disorders were Fanconi's anemia, type I glycogen storage
      disease. Hurler's disease, and severe combined immunodeficiency with ADA
      deficiency. The remaining three children had adenoma without known associated
      disorders. In the children with glycogenosis and Hurler's disease the adenomas
      were multiple. Significant dysplasia occurred in the two children with Fanconi's
      anemia; however, the lesions behaved in a benign fashion--one with regression of
      the tumor after cessation of androgen therapy and the other with nonrecurrence
      after complete resection. Proliferating cell nuclear antigen (PCNA) labeling
      index (LI) of the adenoma arising in patients with Fanconi's anemia was
      significantly greater than the PCNA-LI of adenoma in the other children (mean
      4.1% versus 0.9% of nuclei), approaching the lower end of the spectrum for
      reported hepatocellular carcinoma cases. We emphasize that the worrisome
      pathology that may occur in hepatic adenoma in children, particularly with
      Fanconi's anemia, does not necessarily predict malignant behavior. The
      association of hepatic adenoma with Hurler's disease or severe combined
      immunodeficiency has not been reported previously.

PMID- 7573675
TI  - Pancreatic metaplasia in Barrett's esophagus. An immunohistochemical study.
AB  - While pancreatic metaplasia has been observed in gastric mucosa of patients with
      chronic gastritis, it has not been described in ectopic gastric mucosa. We have
      identified focal clusters of cells resembling pancreatic acinar cells (CPACs) in
      11 of 350 biopsies of Barrett's mucosa from 120 patients with Barrett's esophagus
      enrolled in a clinical efficacy trial of omeprazole versus ranitidine for
      treatment of gastroesophageal reflux disease. Three additional cases from our
      surgical files were also studied. Immunoreactivity for trypsin and chymotrypsin
      was present in the CPACs of all 14 cases, while stains for alpha-amylase and
      lipase were each positive in 12 of 13. A few cells in the CPACs were also
      positive for chomogranins (12 of 13 cases), serotonin (seven of 13 cases),
      somatostatin (three of 12), gastrin (four of 11), and pancreatic polypeptide (two
      of 13). No staining was seen for insulin or glucagon. Ultrastructural studies
      performed in one case showed features of pancreatic exocrine and endocrine (PP
      type) cells in cells within CPACs. These results collectively indicate that the
      CPACs are aggregates of true pancreatic acinar cells admixed with a few endocrine
      cells. This pancreatic parenchyma in Barrett's mucosa is most likely of
      metaplastic origin and could be derived from the transitional zone cells or from
      pluripotent stem cells in the esophageal mucosa or from metaplasia of mucus
      cells. While the development of pancreatic metaplasia in Barrett's esophagus
      appears to be unrelated to drug therapy, the clinical relevance of this
      distinctive histological finding needs further investigation.

PMID- 7573677
TI  - Esophageal submucosal gland duct adenoma.
AB  - An 81-year-old man with a 3-year history of dysphagia underwent endoscopic
      resection of a 1-cm-diameter distal esophageal mass. Examination revealed a
      submucosal neoplasm with a circumscribed growth pattern composed of tubules,
      cysts, and papillae in association with a marked interstitial lymphoid
      infiltrate. The cyst lumens and papillae were lined by two to six layers of
      cytologically bland cuboidal to columnar cells with rare mitotic figures. The
      basal layer of cells was uniformly positive for smooth-muscle actin. Mucin
      positive intracytoplasmic lumens were focally present, but cytoplasmic mucin was
      not seen. There was no evidence of Barrett's metaplastic epithelium. These
      features are similar to those in two, possibly three, previously reported cases
      of esophageal adenomas and bear a resemblance to sialadenoma papilliferum, a rare
      neoplasm of the minor salivary glands. Their clinicopathologic and
      immunohistologic features suggest that these neoplasms derive from the submucosal
      gland ducts. Comparison with the previously reported cases indicates that
      although the proportions of the various components (tubules, cysts, and papillae)
      may vary, all cases appear to pursue a slowly growing, clinically indolent course
      with no evidence of recurrence after complete resection.

PMID- 7573678
TI  - Primary extramedullary plasmacytoma of the liver. A case report.
AB  - We report the first case of primary extramedullary plasmacytoma of the liver. The
      tumor was situated in segment VIII of the liver without extrahepatic extension.
      Histologically, the tumor was composed of sheets of mature plasma cells with
      slight atypia in association with proplasmacytes invading the hepatic parenchyma.
      Neither plasmoblasts nor lymphoplasmacytes were present. Immunohistochemistry
      demonstrated monoclonal IgG and kappa light-chain expression. In situ
      hybridization confirmed the monotypic expression of kappa light-chain mRNA. Bone
      marrow examination revealed no abnormality. After surgery, the IgG kappa spike
      detected in preoperative plasma samples decreased. The patient is disease free 31
      months postoperatively.

PMID- 7573679
TI  - Littoral cell angiosarcoma of the spleen. Case report with immunohistochemical
      and ultrastructural analysis.
AB  - This report describes a case of a malignant vascular tumor of the spleen with the
      morphologic, immunologic, and ultrastructural features observed in splenic sinus
      lining cells (littoral cells). Histological examination showed a well
      differentiated neoplasm forming ectatic blood channels with intraluminal
      papillary fronds. Tumor cells displayed malignant nuclear features and
      hemophagocytosis. Solid neoplastic areas with mitotic figures were present.
      Ultrastructurally, the tumor cells showed the concomitant presence of lysosomes
      and Weibel-Palade bodies. Immunohistochemically, the tumor cells were positive
      for both endothelial (Factor VIII-AG, CD34) and histiocytic markers (cathepsin D,
      lysozyme, alpha-1-antichimotrypsin). Our results indicate that angiosarcoma may
      originate from all the vascular compartments of the spleen, including red-pulp
      sinuses, and may have morphologic and immunophenotypic similarities to littoral
      cell angioma, a recently described benign vascular tumor of the spleen.

PMID- 7573680
TI  - Composite follicular variant of papillary carcinoma and mucoepidermoid carcinoma
      of the thyroid. Report of a case and review of the literature.
AB  - The follicular variant of papillary carcinoma of the thyroid gland is a commonly
      recognized, well-defined entity. However, primary mucoepidermoid carcinoma of the
      thyroid is rare, with only 21 cases reported. We describe a 29-year-old woman who
      presented with a mass in the right lobe of the thyroid. The tumor was classified
      as the follicular variant of papillary carcinoma of the thyroid with several foci
      of mucoepidermoid carcinoma. Both components were invading the capsule and had
      spread to regional lymph nodes. This is the first reported case in which both the
      papillary and mucoepidermoid carcinomas were present in the primary tumor and in
      the metastases.

PMID- 7573681
TI  - Dedifferentiation criteria.

PMID- 7573683
TI  - Carcinoma in mesonephric remnants.

PMID- 7573682
TI  - Primary cerebral malignant lymphomas.

PMID- 7573685
TI  - Solid papillary carcinoma of the breast. A form of intraductal carcinoma with
      endocrine differentiation frequently associated with mucinous carcinoma.
AB  - We report 20 examples of a distinctive form of intraductal papillary carcinoma
      frequently associated with both mucinous carcinoma and infiltrating ductal
      carcinoma, not otherwise specified. All the patients were in the seventh decade
      of life or older. The clinical presentation and macroscopic appearance suggested
      a benign lesion in most cases. The tumors grew in a solid papillary pattern and
      displayed low-grade cytological features as well as intracellular and
      extracellular mucin. Endocrine differentiation was demonstrated by the Grimelius
      stain in 11 of 17 cases and by the chromogranin immunohistochemical technique in
      eight of 14 cases. Lymph node metastases were not observed, but pulmonary
      metastasis occurred in one case. All the tumors were positive for estrogen
      receptors. We postulate that these lesions are the preinvasive counterpart of
      mucinous carcinomas with endocrine differentiation.

PMID- 7573686
TI  - Chromophobe cell carcinoma of the kidney. A clinicopathologic study of 21 cases.
AB  - The clinicopathologic features in a series of 21 chromophobe cell carcinomas are
      reviewed. Patients' ages ranged from 30 to 83 years (mean, 53 years), and the
      number of men and women was roughly equal. Major presenting complaints included
      hematuria, flank pain, and flank mass. All but two tumors were staged as tumor
      node metastasis (TNM) T2N0M0. Histologically, the carcinomas were composed of
      large cells with variably reticulated, translucent cytoplasm. The tumor cells
      could be divided into three types according to the extent and distribution of
      reticulated cytoplasm. Ultrastructurally, these reticulated areas were
      characterized by the presence of large numbers of microvesicles, which appeared
      to be unique to chromophobe cell carcinomas because ultrastructural examination
      of 20 clear cell carcinomas and six granular cell carcinomas failed to reveal
      similar structures. The origin of the vesicles appeared to be from saccular
      outpouchings from the outer mitochondrial membrane. Immunohistochemical studies
      revealed that all the tumors were variably positive for cytokeratins 8, 18, and
      19, and epithelial membrane antigen but negative for vimentin. Flow cytometric
      DNA analysis of eight carcinomas revealed slightly hypodiploid cell populations
      in seven tumors. Of these, four also contained hyperdiploid cell populations.
      Follow-up (6-108 months) of 16 patients revealed all these patients to be alive
      and well. These findings further confirm the concept that chromophobe cell
      carcinoma is a special subtype of renal cell carcinoma in which the presence of
      microvesicles is a characteristic morphologic feature. Furthermore, loss of
      chromosomal DNA may also be a frequent, perhaps unique, feature of chromophobe
      cell carcinoma.

PMID- 7573684
TI  - Pseudosarcomatous myofibroblastic tumor of the urinary bladder in children: a
      study of 11 cases with review of the literature. An Intergroup Rhabdomyosarcoma
      Study.
AB  - Pseudosarcomatous myofibroblastic tumor (PMT) is the result of reactive
      proliferation of myofibroblasts. In children, PMT of the urinary bladder can be
      mistaken for embryonal rhabdomyosarcoma clinically, radiologically, and by light
      microscopy. We are reporting the clinical, histological, and immunohistological
      features of 11 patients with childhood PMT of urinary bladder that were diagnosed
      initially as a sarcoma, usually rhabdomyosarcoma. The morphologic spectrum of PMT
      is broad, with mixtures of myxoid, leiomyomatous, and sclerosing matrix patterns,
      the myxoid type being the most common. The proliferating cells consist of three
      forms of myofibroblastic cells: long spindle cells (type I), intermediate spindle
      cells (type II), and ganglion-like cells (type III), together with various types
      of inflammatory cells. The immunohistologic profile of the proliferating cells
      was characterized by positive reactions to vimentin, muscle-specific actin, alpha
      smooth-muscle actin, polyclonal desmin, and keratin. Ultrastructural studies
      showed myofibroblastic differentiation of the tumor cells. No patients have had
      metastases or local recurrence. Histologic, immunohistochemical, and clinical
      data from 71 cases of PMT, including the 11 cases in this report, confirm the
      benign behavior of these lesions. The etiology of these lesions is unclear,
      including the absence of surgical or other trauma in all of the children.

PMID- 7573687
TI  - Solitary fibrous tumors of soft tissue. A clinicopathologic and
      immunohistochemical study of 12 cases.
AB  - We describe 12 cases of primary soft tissue neoplasms that showed the histologic
      and immunohistochemical features of solitary fibrous tumors of serosal surfaces
      (solitary fibrous mesothelioma, submesothelial fibroma). Nine patients were women
      and three were men whose ages ranged from 28 to 83 years. Seven lesions were
      located in the head and neck region, and the remainder were located in the back,
      buttock, perineum, and groin. The lesions measured from 1 to 6 cm in greatest
      diameter and presented grossly as well-circumscribed, unencapsulated, soft to
      rubbery tissue masses. Histologically they were characterized by a proliferation
      of spindle cells exhibiting a variety of growth patterns, including storiform,
      herringbone, neural with wavy nuclei, and hemangiopericytic admixed with areas of
      sclerosis. In two cases the lesions showed areas of increased cellularity with
      occasionally scattered mitotic figures. Three cases were located adjacent to a
      major salivary gland; in one, entrapment of normal salivary gland acini and ducts
      could be observed at the edges of the lesion. Immunohistochemical studies showed
      positive staining of the spindle cells with CD34 (anti-HPCA-1) and vimentin
      antibodies and negative staining with keratin, actin, desmin, S-100 protein,
      collagen type IV, and factor VIII related antigen. Follow-up from 6 months to 12
      years has shown no evidence of recurrence or metastasis in any of our patients.
      Solitary fibrous tumors appear to represent ubiquitous mesenchymal neoplasms that
      may not be necessarily restricted to serosal surfaces. Identification of these
      lesions is of importance to avoid misdiagnosis with other more aggressive
      conditions in soft tissue locations.

PMID- 7573688
TI  - Accuracy of frozen-section diagnosis of mammographically directed breast
      biopsies. Results of 1,490 consecutive cases.
AB  - The accuracy of intraoperative frozen-section diagnosis of small in situ and
      invasive breast cancers is uncertain. We reviewed the results of 1,490
      consecutive wire-localized breast biopsies from 1,439 patients with nonpalpable
      mammographically detected abnormalities examined by frozen section at Mayo Clinic
      over a 3-year period. The mammographic abnormalities included benign
      calcifications (61 cases), indeterminate calcifications (422 cases), worrisome
      calcifications (54 cases), well-circumscribed nodules (115 cases), irregular
      nodules (473 cases), architectural distortions (52 cases), asymmetry (39 cases),
      well-circumscribed nodules with calcification (12 cases), irregular nodules with
      calcification (75 cases), architectural distortions with calcification (35
      cases), and asymmetry with calcifications (12 cases). We detected 457 carcinomas,
      including 135 in situ and 322 invasive cancers. The invasive carcinomas had a
      mean diameter of 1.07 cm (range, 0.1-3.0 cm), including 191 with diameters of 1
      cm or less (59.3% of cases). In 77 cases (5.2% of total), the diagnosis was
      deferred to permanent sections. Frozen-section accuracy was 97.7%. False-negative
      diagnoses were rendered in 0.5% of cases, and there were no false-positive
      diagnoses. There was no correlation of infiltrating carcinoma diameter and error
      rate. These results indicate that intraoperative frozen section of
      mammographically directed breast biopsies provides accurate and reliable
      diagnoses.

PMID- 7573689
TI  - Chondroid lipoma, a tumor of white fat cells. A brief report of two cases with
      ultrastructural analysis.
AB  - Chondroid lipoma is a recently described variant of lipoma with unusual
      morphologic features. Although classified as a fatty neoplasm, its phenotype is
      uncertain because it has not been determined whether cartilage is a real
      component or only simulated by light microscopy and whether the adipocytes
      demonstrate white or brown fat differentiation, issues that can be resolved only
      by electron microscopy. We present two cases of chondroid lipoma that
      ultrastructurally showed abundant intracytoplasmic lipid and glycogen and
      numerous pinocytotic vesicles, characteristic of white adipocytes. These findings
      support the conclusion that these tumors are composed solely of fat without true
      cartilage differentiation.

PMID- 7573690
TI  - Thymic carcinoid with prominent mucinous stroma. Report of a distinctive
      morphologic variant of thymic neuroendocrine neoplasm.
AB  - Four cases are described of a distinctive morphologic variant of thymic carcinoid
      that was characterized by abundant stromal mucin admixed with the neuroendocrine
      elements resulting in a histologic picture reminiscent of metastatic mucin
      secreting carcinoma. The patients were three men and a woman, aged 22 to 43
      years. The tumors presented with symptoms of chest discomfort, cough, and dyspnea
      and were described as large anterior mediastinal masses on chest radiographs and
      computerized scans. Histologically, all cases showed nests and strands of tumor
      cells embedded in an abundant lightly eosinophilic, mucinous stroma with small
      cellular clusters as well as scattered single tumor cells seen floating in the
      mucin. The mucinous matrix was negative for periodic acid Schiff's and
      mucicarmine stains; alcian blue stains at pH 2.5 showed strong positivity of the
      mucinous material; this reaction was abolished by treatment with hyaluronidase,
      indicating the presence of nonepithelial stromal mucosubstances.
      Immunohistochemical stains showed strong positivity of the tumor cells with CAM
      5.2, chromogranin, synaptophysin, and neuron-specific enolase, and negative
      staining with carcinoembyronic antigen and epithelial membrane antigen. Electron
      microscopy done in one case showed abundant dense-core cytoplasmic neurosecretory
      granules; there was no evidence of glandular secretory activity by the tumor
      cells. The tumors in two patients behaved in a highly aggressive fashion, with
      invasion of the chest wall, recurrence, and metastases to the lungs, pleura, and
      axillary, retroperitoneal, and mesenteric lymph nodes. Thymic carcinoid should be
      considered in the differential diagnosis of mediastinal neoplasms displaying
      prominent mucinous features. Application of immunostains and electron microscopy
      will be of value for establishing the correct diagnosis in this setting.

PMID- 7573691
TI  - Giant cell angiofibroma. A distinctive orbital tumor in adults.
AB  - A series of seven cases of a previously unrecognized potentially recurrent tumor
      occurring in the orbit of adult patients is reported. This lesion shows
      histologic appearances intermediate between, but distinct from, solitary fibrous
      tumor and giant cell fibroblastoma of soft tissue. Morphologically it is
      characterised by a richly vascularized, patternless spindle-cell proliferation
      containing pseudovascular spaces. Multinucleate giant cells (often of floret
      type) and cells with large, rounded nuclei are present both in the cellular areas
      and also lining the pseudovascular spaces. The stroma is variably collagenized or
      sometimes myxoid. Immunohistochemically, the tumor cells exhibit positivity for
      vimentin and CD34. Follow-up in five cases (median duration 24 months) revealed
      local recurrence in one patient and persistent tumor in another. The clinical and
      morphologic features enable distinction of this lesion from both solitary fibrous
      tumor and giant cell fibroblastoma, and we suggest the designation "giant cell
      angiofibroma of the orbit".

PMID- 7573692
TI  - Follicular Hodgkin's disease.
AB  - We describe four cases of Hodgkin's disease that presented histologically as
      purely follicular lesions. The Reed-Sternberg (RS) cells were of classic and
      lacunar type and had the phenotype of usual Hodgkin's disease (CD30 and CD15
      positive) but also expressed B-cell antigens (CD20 and CD79a). In each case the
      follicles consisted principally of mantle-zone B cells, which enclosed the RS
      cells; the follicle centres were atrophic, usually eccentrically placed, and did
      not contain RS cells. Fifteen cases of typical nodular sclerosing Hodgkin's
      disease were reviewed in parallel. B-cell antigen expression by RS cells was
      found in 10 cases (66%), and RS cells were present in follicular mantles in 10
      cases. These findings suggest that some RS cells may be derived from B cells in
      the follicular mantle.

PMID- 7573693
TI  - Lymphomatoid granulomatosis. Evidence of immunophenotypic diversity and
      relationship to Epstein-Barr virus infection.
AB  - We studied open-lung biopsies from 17 patients with pulmonary lymphomatoid
      granulomatosis (LYG) using paraffin-section immunostains and Epstein-Barr virus
      (EBV) RNA in situ hybridization to assess the phenotype of these unique tumors
      and to clarify the role of EBV infection. Histologically, all cases demonstrated
      the characteristic mixed mononuclear cell infiltrate of lymphomatoid
      granulomatosis with variable numbers of cytologically atypical large lymphoid
      cells in a background of small lymphocytes. Paraffin-section immunostains in all
      cases showed a predominance of T lymphocytes. A minor population of CD20-positive
      large B lymphocytes was identified in 11 cases; immunoglobulin light-chain
      restriction was demonstrated in four of these and immunoglobulin gene
      rearrangements in another case. Nuclear labelling for EBV RNA was detected in 10
      of these 11 cases and was confined to the population of large B lymphocytes.
      Staining for CD20 was absent in the remaining six cases, as was nuclear labeling
      for EBV RNA. However, the large atypical lymphoid cells stained for T-cell
      lineage-specific antibodies in three of these cases. We conclude that some cases
      of lymphomatoid granulomatosis are B-cell lymphoma associated with EBV infection,
      whereas others are of T-cell origin and are probably unrelated to EBV infection.

PMID- 7573694
TI  - Pathologic features of nodular lymphocyte predominance Hodgkin's disease in
      extranodal sites.
AB  - We describe the gross and histologic features of nodular lymphocyte predominance
      Hodgkin's disease (NLPHD) occurring in extranodal sites. Fifty-one specimens of
      NLPHD from 16 patients were studied. The sites of involvement were the spleen,
      liver, tonsil, salivary glands, skin, colon, soft tissue, and bone marrow, and
      the morphologic features were similar to those described in node-based NLPHD,
      including characteristic lymphocytic and/or histiocytic (L&H) cells that were
      easily identified in a background of a nodular proliferation of small lymphocytes
      and histiocytes. In the spleen, the normal architecture was generally preserved,
      and the tumor was found predominantly in the white pulp; the red pulp was rarely
      involved. In the liver, the tumor involved both the portal and parenchymal areas.
      In the tonsil, the lympohproliferation closely resembled the typical appearance
      of NLPHD in a lymph node. In all specimens with materials available for
      immunohistochemical studies, there were demonstrable L&H cells with an
      immunophenotype similar to node-based NLPHD, that is, CD45-positive, CD20
      positive, and CD15-negative. The unique morphologic and immunologic
      characteristics of NLPHD are preserved in extranodal sites and allow its
      distinction from classic Hodgkin's disease and other lymphoproliferative
      malignancies that may occur in extranodal sites.

PMID- 7573695
TI  - Polyneuropathy associated with nerve angiomatosis and multiple soft tissue
      tumors. A newly recognized syndrome.
AB  - We report the case of a 33-year-old woman affected by a severe sensorimotor
      polyneuropathy and multiple soft tissue tumors since childhood. In the biopsied
      sural nerve, there was a striking vascular proliferation of small vessels. Three
      subcutaneous nodules were biopsied and disclosed pathologic findings resembling
      those found in tumors in infantile myofibromatosis. One of the three biopsied
      subcutaneous nodules was intimately contiguous with a peripheral nerve. The
      ultrastructural features and immunohistochemical reactivity of the soft tissue
      tumors and the vessels proliferating in the nerve suggested a common cellular
      differentiation. The finding of a diffuse polyneuropathy associated with
      widespread angiomatosis in nerve and multiple soft tissue tumors suggests that
      these are not coincidental findings, but a manifestation of a syndrome perhaps
      not previously recognized.

PMID- 7573696
TI  - Minnie G. would spin in her grave.

PMID- 7573697
TI  - CD34 positivity in solitary fibrous tumor of the liver.

PMID- 7573698
TI  - Renal epithelial dysplasia.

PMID- 7573699
TI  - Antibodies to hemorrhagic fever viruses in domestic livestock in Niger: Rift
      Valley fever and Crimean-Congo hemorrhagic fever.
AB  - A repository of domestic animal sera collected in Niger between 1984 and 1988 was
      assayed for antibody against two zoonotic hemorrhagic fever viruses known to be
      present in the West African Sahel. A total of 2,540 serum samples from 2,324
      cattle, sheep, goats, and camels were tested by an IgG-specific enzyme-linked
      immunosorbent assay (ELISA) and the 80% plaque reduction neutralization test
      (PRNT80) for Rift Valley fever (RVF) virus antibody. Of the 2,540 sera tested for
      RVF-specific IgG antibody, 1,676 sera from cattle, sheep, and goats were examined
      for RVF-specific IgM antibody by ELISA. A subset of 2,263 sera were examined for
      evidence of Crimean-Congo hemorrhagic fever (CCHF) virus antibody by an IgG
      specific ELISA. Antibody against CCHF virus was found to be most prevalent in
      adult cattle (422 of 732 or 57.7% positive) sampled at nine locations in the
      Niamey area. The highest prevalence for RVF neutralizing antibodies was found in
      camels from the Agadez Department with 67 (47.5%) of 141 positive. The results
      indicate that both CCHF and RVF viruses are circulating in Niger and are
      potential zoonotic health risks.

PMID- 7573701
TI  - Detection of hepatitis E virus infections among domestic swine in the Kathmandu
      Valley of Nepal.
AB  - The prevalence of hepatitis E virus (HEV) infections among 55 domestic swine
      living in the Kathmandu Valley of Nepal was investigated. Sera and stool
      specimens were collected from 47 free-roaming swine and examined for the presence
      of HEV genomic sequences by the reverse transcription-polymerase chain reaction.
      Sera from these animals, as well as sera from eight other swine, were also
      examined for the presence of HEV-specific antibodies by an enzyme-linked
      immunosorbent assay and by a fluorescent antibody blocking assay. Hepatitis E
      virus RNA was detected in the sera and/or stool of three of 47 swine, while HEV
      specific antibodies were detected in 18 of 55 swine. These results indicate that
      HEV is a zoonotic virus, and that swine are among its natural hosts.

PMID- 7573702
TI  - The risk of viral hepatitis A, B, C, and E among North American missionaries.
AB  - The seroprevalence and incidence of hepatitis A, B, C, and E virus infection were
      determined among North American missionaries (n = 328) serving in various
      geographic locations between 1967 and 1984. The mean age of subjects at entry
      into the study was 39.7 years (range 5-73 years); 65% were female; 89% had lived
      outside the United States before the study began. Seventy-eight percent of
      subjects served in sub-Saharan Africa during the study. At initial evaluation,
      50.9% of the subjects had antibodies to hepatitis A virus (total anti-HAV), 8.5%
      to hepatitis B virus core antigen (total anti-HBc), 0.6% to hepatitis C virus
      (total anti-HCV by second-generation immunoblot assay), and 0% to hepatitis E
      virus (IgG anti-HEV). After an average period of service of 7.3 years (2,396
      person-years total), 5.8% of the missionaries seroconverted to anti-HAV, 5.5% to
      anti-HBc, 0.6% to anti-HCV, and 0% to anti-HEV. This study indicates a relatively
      low risk of hepatitis C and E virus infection among missionaries while confirming
      the previously reported high risk of hepatitis A and B virus infection. Hepatitis
      A and B vaccination is recommended for long-term travelers to developing
      countries.

PMID- 7573700
TI  - Evidence for the existence of Puumula-related virus among Clethrionomys rufocanus
      in Hokkaido, Japan.
AB  - We conducted field surveys of indigenous rodent species in Hokkaido, Japan from
      1980 to 1993. Serum samples were collected from 663 rodents, including
      Clethrionomys rufocanus, Apodemus speciosus, A. argenteus, and C. rutilus.
      Antibody to hantavirus was determined by the protein G antibody assay. Positive
      C. rufocanus were detected in seven of eight collection sites, but no antibody
      was detected in the remaining rodent species. To reveal the serotype of the
      circulating virus in C. rufocanus, antibody titers to Hantaan, Seoul, Puumala,
      and Prospect Hill viruses were compared by means of the focus reduction
      neutralization test. The titers in positive sera were extremely high to the
      Sotkamo strain of Puumala virus. Results were confirmed by the reverse
      transcriptase-polymerase chain reaction, and suggested that Puumala-related
      viruses are in circulation among C. rufocanus populations in Hokkaido.

PMID- 7573703
TI  - Evidence implicating nymphal Ixodes pacificus (Acari: ixodidae) in the
      epidemiology of Lyme disease in California.
AB  - To clarify the role of nymphal versus adult western black-legged ticks (Ixodes
      pacificus) in the epidemiology of Lyme disease, the seasonal distribution,
      abundance, and spirochetal infection rates in these stages, and the seasonal
      occurrence of ticks biting humans and of incident cases of Lyme disease were
      determined in northern California. Although their seasonal activity periods
      overlapped for about one-third of the year, nymphs and adults predominated in
      different seasons, the former from late spring to summer and the latter from fall
      to early spring. At one site, four (4%) of 100 adults from low vegetation
      bordering a hardwood forest and 44 (13.6%) of 324 nymphs from leaf litter in the
      forest were found to contain Borrelia burgdorferi. Biting-collection records
      revealed that nymphs attach to people more commonly than recognized previously;
      I. pacificus nymphs comprised 12.5% of 967 ticks of various species and stages
      and 42% of all nymphs submitted for identification. Attachments by nymphs
      occurred primarily between April and August, which coincided with the seasonal
      occurrence of most incident cases of Lyme disease. Collectively, these findings
      strongly implicate the nymphal stage of I. pacificus as the primary vector of B.
      burgdorferi to humans in this region.

PMID- 7573704
TI  - Short report: an outbreak of trichinosis in Navarra, Spain.
AB  - Trichinosis is an infection contracted by ingestion of meat containing viable
      larvae of the nematode Trichinella spiralis. This report concerns an outbreak of
      infections with this parasite in Navarra, Spain that was associated with home
      prepared pork products. After the detection of a person with trichinosis, a study
      of all subjects that had ingested meat from the presumably infected pork was
      carried out. Forty-four members of eight families were enrolled in the study. Ten
      had symptoms suggestive of trichinosis, 20 had hypereosinophilia, and 15 had
      positive serologic test results for anti-Trichinella antibodies. Three groups
      could be distinguished according to the kind of product each subject had ingested
      (pork sausage, blood pudding, and loin). Twelve months later, all had a normal
      eosinophil count and a negative serology.

PMID- 7573705
TI  - Evaluation of alternate methods of rapid assessment of endemicity of Onchocerca
      volvulus in communities in southern Cameroon.
AB  - Potential diagnostic indicators of onchocerciasis (subcutaneous nodules,
      depigmentation or leopard skin, microfilaruria, diethylcarbamazine patch test
      positivity, excoriations, and pruritus) were evaluated in a rain forest region of
      southern Cameroon for usefulness in rapid assessment of onchocerciasis endemicity
      in communities. Thirty-two study villages were selected, representing high,
      intermediate, and low prevalence levels, and 846 adult male residents of these
      communities 20 or more years of age were examined according to a defined
      protocol. Skin snips (from each iliac crest) served as the reference standard.
      Skin snip positivity was 75.5%; the effect of age was minimal. Leopard skin and
      nodules showed the strongest correlation with both the skin snip prevalence and
      community microfilarial load, as reflected by the adult male study population. We
      selected > or = 20% nodules or > or = 20% leopard skin as the most appropriate
      local criteria for assigning a community to high priority for control, which
      corresponds to a > or = 90% skin snip prevalence in adult males. While this
      criteria should not be applied to regions with savannah onchocerciasis, we
      believe the methodology can and should be used to determine appropriate
      diagnostic indicators for rapid assessment of Onchocerca volvulus endemicity in
      regions with different dynamics of transmission and clinical expression of
      disease.

PMID- 7573708
TI  - Lymphadenopathy as the first sign of human cutaneous infection by Leishmania
      braziliensis.
AB  - This paper describes the presence of transitory lymphadenopathy as an initial
      sign of cutaneous leishmaniasis, and sometimes the only manifestation of
      Leishmania braziliensis infection. Ten patients with lymphadenopathy living in an
      area of L. braziliensis transmission had Leishmania cultivated from their lymph
      nodes previous to any other manifestation of cutaneous leishmaniasis. Seven of
      the 10 developed leishmanial ulcers later in the course of infection, whereas
      lymphadenopathy regressed in three cases and no other sign of infection
      developed. Results of tests for anti-Leishmania antibodies and an intradermal
      skin test were positive in four and five patients, respectively, at the time of
      the diagnosis. The documentation of Leishmania amastigotes in the lymph nodes
      before any clinical evidence of cutaneous disease indicates that early spread of
      L. braziliensis from the skin to lymph nodes occurs before a local lesion
      develops. All medical doctors examining patients coming from endemic areas of
      leishmaniasis should be aware that lymph node enlargement, even in the absence of
      a typical ulceration, may be indicative of leishmanial infection and warrants
      further investigation.

PMID- 7573709
TI  - Efficacy of antivenom in the treatment of severe local envenomation by the hump
      nosed viper (Hypnale hypnale).
AB  - In Sri Lanka, the usual treatment for severe local envenomation by the hump-nosed
      viper (Hypnale hypnale) is with polyspecific snake antivenom. We carried out a
      prospective, randomized, placebo-controlled, single-blind clinical trial to
      determine the efficacy and safety of polyspecific snake antivenom in the
      treatment of severe local envenomation by this snake. Sixty-three patients with
      signs and symptoms of local envenomation by the hump-nosed viper Lanka were
      randomized to receive either polyspecific snake antivenom or normal saline. The
      two groups were similar in age, sex, time of presentation to hospital, and degree
      of envenomation. There was no significant difference between the antivenom and
      placebo groups in the time taken for complete resolution of the local
      envenomation (5.52 days versus 4.77 days; P = 0.53, by the Mann-Whitney U test).
      There was a 44.82% incidence of adverse reactions associated with treatment with
      antivenom. We conclude that polyspecific snake antivenom is not indicated for
      severe local envenomation by the hump-nosed viper.

PMID- 7573706
TI  - Efficacy of stool examination for detection of Strongyloides infection.
AB  - To determine the efficacy of stool examination for detection of Strongyloides
      infection, 1,350 stool samples collected in Japan, Brazil, and Thailand were
      examined by four different methods (direct fecal smear, formalin-ether
      concentration. Harada-Mori filter paper culture, and agar plate culture). The
      newly developed agar plate culture method was highly effective; more than 96% of
      the positive cases were diagnosed by this method. The coprologic examination,
      however, was not sensitive enough for detecting chronic infections because more
      than 40% of the positive cases were overlooked even when persons with proven
      Strongyloides infection were re-examined several months later without intervening
      treatment. Therefore, it is essential to examine stool samples repeatedly to
      achieve a correct diagnosis, and even so, it is important to note that a negative
      result does not necessarily indicate the unequivocal absence of the infection.

PMID- 7573710
TI  - A case report of colonic ileus due to eosinophilic nodular lesions caused by
      Gnathostoma doloresi infection.
AB  - Gnathostomiasis is primarily a disease of the skin characterized as creeping
      eruption or mobile erythema. However, larval Gnathostoma sometimes migrate into
      an unexpected site to elicit serious illness. Here we describe a case of colonic
      ileus caused by Gnathostoma doloresi. The patient was a 57-year-old man living in
      Miyazaki Prefecture, Japan, which is known as an area endemic for this parasite.
      One week after having eaten a few slices of the flesh of a snake (Agkistrodon
      halys), he developed severe abdominal pain. An abdominal radiograph revealed
      multiple gas-fluid levels with a distended bowel of an inverted U shape. A barium
      enema revealed a tumor in the ascending colon near the hepatic flexure that was
      surgically removed by simple colonic resection. An oblique section of a parasite
      surrounded by massive infiltration of eosinophils was found by postoperative
      histopathologic examination. The entire body of the advanced third-stage larva of
      G. doloresi was dissected from a specimen-embedded paraffin block.

PMID- 7573711
TI  - Selective diethylcarbamazine chemotherapy for control of Bancroftian filariasis
      in two communities of Tanzania: compared efficacy of a standard dose treatment
      and two semi-annual single dose treatments.
AB  - The efficacy of two strategies for control of Bancroftian filariasis using
      selective rather than community-wide diethylcarbamazine (DEC) chemotherapy was
      evaluated and compared in two endemic communities of north-eastern Tanzania, with
      pretreatment microfilariae (mf) prevalences of 22% and 38%, and geometric mean
      intensities (GMIs) of 668 mf/ml and 735 mf/ml of blood. All mf-positive cases in
      the first community were offered treatment with 6 mg of DEC/kg of body weight a
      day for 12 days (group 1), and those in the second community were offered
      treatment with two doses of 6 mg of DEC/kg of body weight at an interval of six
      months (group 2). The effect of treatment was followed both among those treated
      and at the community level. In treated individuals, there was a rapid decrease in
      the mf load that was significantly greater among those receiving the 12-day
      standard dose. One year after the start of treatment, the mf clearance rates were
      59% and 39% and the GMIs were reduced by 99% and 97% among treated individuals in
      groups 1 and 2, respectively. However, at the community level, the mf prevalences
      were 16.3% and 27.9% (reduced by 27% and 26%) and the GMIs were 129 mf/ml and 224
      mf/ml (reduced by 81% and 70%) one year after the start of treatment with the two
      regimens, respectively, suggesting that transmission continued at a significant
      level in the villages after treatment. The limitations of selective chemotherapy
      are discussed, and it is argued that strategies based on mass DEC chemotherapy
      would be more effective in reducing the microfilarial load in the community and
      thereby in reducing transmission.

PMID- 7573707
TI  - Comparison of the polymerase chain reaction and serology for the detection of
      canine visceral leishmaniasis.
AB  - The polymerase chain reaction (PCR) and serology was evaluated for the diagnosis
      of canine visceral leishmaniasis in Bahia, Brazil in a study of 125 dogs. The PCR
      was 100% sensitive in 25 dogs that had Leishmania demonstrated by either culture
      or hamster inoculation. It was 100% specific for 35 dogs from the northeastern
      United States, all were PCR negative. However, 22 of 54 Brazilian dogs that were
      culture-hamster inoculation-negative were positive by PCR. The nature of the PCR
      product was identified by hybridization with specific Leishmania probes. Whereas
      the sensitivity of serology in relationship to infection, as determined by
      hamster or culture assay was more than 80%, sensitivity of serology was only 63%
      when compared with PCR. These results raise questions about the use of serology
      to detect Leishmania infection in dogs, and suggest that the PCR might serve as a
      better gold standard to define Leishmania infection than culture or hamster
      inoculation.

PMID- 7573712
TI  - Characterization of the immune response in subjects with self-healing cutaneous
      leishmaniasis.
AB  - In patients with cutaneous leishmaniasis in areas of Leishmania braziliensis
      transmission, ulcers may heal without therapy. In the present study, we evaluated
      the T cell responses of 10 subjects who two years earlier had a rapidly (less
      than three months) self-healing cutaneous disease. The immunologic responses of
      these cases were determined by intradermal skin test, measurements of antibodies,
      lymphocyte proliferative responses, and interferon-gamma (IFN-gamma) production
      in cultures stimulated with Leishmania antigens. These data were compared with
      those observed in 10 other patients with active cutaneous and mucosal
      leishmaniasis. Evidence of strong lymphocyte blastogenesis and IFN-gamma
      production was observed in eight of 10 patients with self-healing cutaneous
      leishmaniasis, with stimulation indices ranging from 32 to 506, and IFN-gamma
      levels ranging from 500 to 2,900 pg/ml. The mean +/- SD stimulation index of the
      lymphocyte proliferative responses (288 +/- 247) and the mean +/- SD of IFN-gamma
      production after stimulation with Leishmania antigen (970 +/- 960 pg/ml) in
      subjects with self-healing cutaneous leishmaniasis were similar (P > 0.05) to
      those observed in patients with mucosal disease (stimulation index = 308 +/- 282
      and IFN-gamma level = 838 +/- 819 pg/ml). These responses were higher (P < 0.01)
      than those observed in patients with active cutaneous leishmaniasis (stimulation
      index = 50 +/- 82 and IFN-gamma level = 264 +/- 336 pg/ml).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7573713
TI  - Japanese encephalitis virus-specific proliferative responses of human peripheral
      blood T lymphocytes.
AB  - The T lymphocytes play an important role in prevention and recovery from viral
      infections. To characterize T lymphocyte responses to Japanese encephalitis (JE)
      virus infections, we analyzed JE virus-specific T lymphocytes in peripheral blood
      mononuclear cells (PBMC) obtained from seven JE patients and 10 vaccinees who had
      received a formalin-inactivated, purified JE virus vaccine (Biken vaccine). These
      PBMC were examined for proliferative responses against live JE virus, a
      glutaraldehyde-fixed lysate of cells infected with JE virus, and extracellular
      particles (EPs; subviral membrane vesicles released from cells infected with
      recombinant vaccinia viruses encoding the JE virus premembrane and envelope
      proteins). Japanese encephalitis virus-specific T cell proliferation was
      demonstrated with PBMC from both patients and vaccinees after stimulation with
      infectious JE virus or the lysate of JE virus-infected cells. Proliferating PBMC
      included CD4+ T lymphocytes and CD8+ T lymphocytes in responses to either form of
      JE viral antigens. Responses to EPs were observed only with PBMC from some
      American vaccinees whose PBMC also responded to the virus and lysate. These
      results indicate that JE virus infection and immunization with an inactivated JE
      vaccine induce JE virus-specific CD4+ and CD8+ T memory lymphocytes that can be
      induced to proliferate by infectious JE virus and noninfectious JE antigens.

PMID- 7573714
TI  - Evidence of HLA class II association with antibody response against the malaria
      vaccine SPF66 in a naturally exposed population.
AB  - The antibody response against the malaria vaccine SPf66 and against
      circumsporozoite (CS) protein has been tested in immune adults from a malaria
      endemic area in Papua New Guinea. All individuals were genotyped for the HLA
      class II DQB1 and DRB1 loci, and the humoral response was analyzed with respect
      to the identified class II alleles. At each locus, only three alleles were
      frequent, namely DRB1*11, *15, and *16, and DQB1*0301, *0502, and *0601.
      Antibodies against SPf66 and CS protein were found in 84% and 79% of the
      individuals, respectively. A strong negative association was detected between the
      humoral response against SPf66 and DRB1*15 and DQB1*0601. A positive association
      of the response was observed with DRB1*11 and DQB1*0301. After analysis with a
      multiple regression model in which all alleles were included simultaneously, only
      DRB1*15 remained significantly associated with low antibody responses. This
      suggests that nonresponders may be expected after immunization with SPf66 in
      certain populations.

PMID- 7573715
TI  - Differential recognition of microfilarial chitinase, a transmission-blocking
      vaccine candidate antigen, by sera from patients with Brugian and Bancroftian
      filariasis.
AB  - We examined the reactivity of human sera with recombinant microfilarial chitinase
      and with the antigenic determinant on the native parasite molecule identified by
      monoclonal antibody (MAb) MF1. In Brugian filariasis, the MF1 epitope is
      preferentially recognized by residents of endemic areas who remain
      amicrofilaremic and asymptomatic despite lifelong exposure to filarial worms.
      Reactivity with filarial chitinase and its MF1 epitope inversely correlates with
      microfilaremia levels in Bancroftian filariasis and is associated with a
      prolonged amicrofilaremic state following a single course of treatment with
      diethylcarbamazine. Chitinase does not appear to be a target of human antibodies
      that promote the adherence of cells to microfilariae, even though MAb MF1 itself
      promotes antibody-dependent, cell-mediated cytotoxic (ADCC) reactions that kill
      microfilariae in vitro. Such ADCC reactions are most often mediated by sera from
      amicrofilaremic patients with chronic elephantiasis that contain low or
      undetectable levels of IgG antibodies to chitinase. In contrast, antibodies to
      the MF1 epitope on this microfilarial stage-specific antigen are mostly present
      in amicrofilaremic donors without clinical lymphatic disease. These observations
      indicate that antibodies to the MF1 epitope of microfilarial chitinase reflect
      some degree of immune resistance to microfilaremia in a subgroup of patients with
      asymptomatic lymphatic filariasis. The amicrofilaremic state of individuals with
      chronic lymphatic disease appears to be mediated by reactivity to a different
      parasite antigen(s).

PMID- 7573716
TI  - Rosette formation by Plasmodium coatneyi-infected erythrocytes of the Japanese
      macaque (Macaca fuscata).
AB  - We studied in vitro the spontaneous rosette formation by red blood cells of a
      Japanese macaque infected with Plasmodium coatneyi, which occurred after 30 hr of
      incubation. Rosette formation involved 88% of parasitized red blood cells
      (PRBCs). Spontaneous rosettes were formed when the ring-stage parasites developed
      into late trophozoites or schizonts. A rosette usually consisted of a PRBC
      surrounded by three or more uninfected erythrocytes. Electron microscopic
      examination revealed that interaction with adjacent uninfected erythrocytes in
      rosettes appeared to be mediated by knobs of PRBCs. Protruding ends of these
      knobs attached to the membranes of adjacent uninfected erythrocytes. In the
      present study, we have also obtained evidence that another pattern of cell
      adhesion was mediated by flat and focal electron-dense knobs that had formed on
      the membranes of PRBCs.

PMID- 7573717
TI  - Short report: density of Lyme disease spirochetes within deer ticks collected
      from zoonotic sites.
AB  - We determined whether the density of Lyme disease spirochetes varied between
      individual host-seeking deer ticks. Guts were dissected from 30 adult Ixodes
      dammini collected from three intensely zoonotic coastal Massachusetts sites, and
      the number of Borrelia burgdorferi present was estimated by a modified counting
      technique using indirect immunofluorescence. A median of 1,925 spirochetes was
      observed; ticks from the three sites contained similar numbers of spirochetes. No
      tick contained more than 4,500 spirochetes. Initial experimental reports
      establishing the efficiency of spirochetal transmission may have been based on
      ticks with a uniform spirochetal density, and extrapolations from these studies
      may thus overestimate the infectivity of host-seeking ticks in nature.

PMID- 7573719
TI  - Efficacy of ciprofloxacin in enteric fever: comparison of treatment duration in
      sensitive and multidrug-resistant Salmonella.
AB  - The efficacy of two regimens of ciprofloxacin was compared in a randomized study
      conducted on 69 patients with enteric fever, 52.2% of whom had infection with
      multidrug-resistant (MDR) strains of Salmonella typhi or S. paratyphi. Patients
      were randomly assigned to two regimens (10 days versus 14 days) of ciprofloxacin
      (500 mg twice a day). The mean +/- SD time required for defervescence was similar
      for both regimens (4.2 +/- 1.9 days in the 10-day group and 4.9 +/- 2.6 days in
      the 14-day group). A 100% cure was observed in each treatment group and no
      serious side effects were observed. Relapse occurred in two patients (14-day
      regimen). Only one patient (14-day regimen) had growth of S. typhi in stool
      culture at the time of the first follow-up three days after completion of
      therapy. Follow-up studies on available patients on two, six, and 12 months after
      completion of therapy revealed that all patients had negative stool cultures for
      S. typhi and S. paratyphi. This study indicates that ciprofloxacin may be
      recommended as an initial therapy for enteric fever for adult men and nonpregnant
      and nonlactating women in areas where MDR strains of S. typhi and S. paratyphi
      are prevalent, and that 500 mg twice a day of the drug given for 10 days is as
      effective as 14 days at the same dosage.

PMID- 7573720
TI  - Radioimmunoguided surgery in primary colorectal carcinoma: an intraoperative
      prognostic tool and adjuvant to traditional staging.
AB  - BACKGROUND: The prognostic value of traditional staging classification for
      colorectal cancer has changed little since Dukes created the first staging
      scheme. Some patients with known metastatic disease are long-term survivors,
      while other patients with local disease die early. New intraoperative cancer
      detection technology, the radioimmunoguided surgery (RIGS) system, is being
      studied as a tool to aid in prediction of patient outcome. PATIENTS AND METHODS:
      Thirty-one patients with primary colorectal cancer were injected with the
      monoclonal antibody CC49, which was radiolabeled with iodine 125 (125I). A hand
      held gamma-detecting probe was used at surgery to detect the radiolabeled
      antibody. Patients were classified as to the presence or absence of 125I-CC49
      positive residual tissue at the close of surgery. Patient survival was analyzed.
      RESULTS: Follow-up ranged from 30 to 54 months. Survival of 11 stage I or II
      patients was longer than in 20 stage III or IV patients (P = 0.019). All 14
      patients cleared of RIGS-positive tissue were alive at last follow-up, while 15
      of 17 RIGS-positive patients died of their disease (P < 0.0001). CONCLUSIONS: The
      RIGS system used during surgery provides the surgeon with immediate prognostic
      information on patients with colorectal cancer and supplements traditional
      pathologic staging.

PMID- 7573718
TI  - Parasite viability during treatment of severe falciparum malaria: differential
      effects of artemether and quinine.
AB  - The effect of artemether (AR) and quinine (QN) on parasite viability ex vivo was
      compared in children being treated for severe Plasmodium falciparum malaria.
      Parasitized blood taken at intervals during treatment was cultured in vitro, and
      parasite development was assessed microscopically. Parasite viability (defined as
      the proportion of circulating rings developing to early schizonts) was 56.8% in
      the AR group (n = 7) 6 hr after the start of treatment, compared with 93.3% for
      QN (n = 6; P = 0.015). Even after 24 hr of QN treatment, parasite viability was
      not significantly reduced in five patients. These ex vivo findings, which confirm
      previous observations of the stage-specific effects of these drugs against P.
      falciparum, suggest that AR may be superior to QN in the treatment of severe
      malaria.

PMID- 7573721
TI  - A prospective study of tumor recurrence and the acute-phase response after
      apparently curative colorectal cancer surgery.
AB  - BACKGROUND: Approximately 70% of patients who are going to develop tumor
      recurrence following curative colorectal surgery do so within 24 months of
      surgery. PATIENTS AND METHODS: The relationship was prospectively examined
      between an ongoing acute-phase response and subsequent clinical relapse in 36
      colorectal cancer patients who had undergone a curative resection. Approximately
      4 months after their operation, patients were grouped according to the presence
      (n = 15) or absence (n = 21) of an acute-phase response (C-reactive protein > 5
      mg/L) and were followed-up for a minimum of 24 months. RESULTS: Age, tumor site,
      and serum carcinoembryonic antigen concentrations were similar in both groups.
      There was a significantly higher recurrence rate in patients with an acute-phase
      response (11 of 15) compared to those with no acute-phase response (2 of 21, P <
      0.01). CONCLUSIONS: These results are consistent with the presence of an acute
      phase response being an important predictive factor in the early stages of tumor
      recurrence in patients who have had apparently curative colorectal surgery.

PMID- 7573722
TI  - Interval mammography after needle localization biopsy of breast abnormalities
      that are pathologically benign.
AB  - BACKGROUND: Needle localization biopsy is commonly performed for the diagnosis of
      mammographic abnormalities. Routine specimen radiography is generally
      recommended, but the value of routine short-interval postbiopsy mammography has
      not been analyzed. PATIENTS AND METHODS: We performed a retrospective review of
      299 consecutive localized biopsies in 286 women from March 1989 to November 1993.
      Of these biopsies, 217 from the basis for this study; all yielded a benign
      pathologic diagnosis and had both specimen radiography and 3-month interval
      mammograms performed. RESULTS: A total of 192 (88%) of postbiopsy mammograms were
      interpreted as negative, while 22 (10%) were suspicious. Three patients had
      second biopsies and all had benign diagnoses, 16 had follow-up mammograms that
      were interpreted as normal or stable, and 3 patients were lost to follow-up. A
      suspicious postbiopsy mammogram had no significant relationship to initial
      mammographic abnormality or pathologic diagnosis, but did correlate with specimen
      radiograph interpretation (P = 0.02) by chi-square comparison). CONCLUSIONS: In a
      series of needle localization biopsies with intraoperative specimen radiography,
      postbiopsy mammography failed to reveal any missed cancers. Short-interval follow
      up mammography is unnecessary to assess for residual abnormalities when specimen
      radiography confirms excision of the abnormality.

PMID- 7573723
TI  - Immediate biopsy versus observation for abnormal findings on mammograms: an
      analysis of potential outcomes and costs.
AB  - BACKGROUND: The increased usage of screening mammography has led to an increase
      in the number of needle localized breast biopsies. The perceived low yield of the
      biopsies has caused concern about the costs and effectiveness of this procedure.
      Arguments have centered on what is the appropriate true-positive rate for
      screening mammography, and which abnormal findings may be observed rather than
      tested immediately. METHODS: A decision analysis was done to help answer these
      questions. Factors evaluated included age of patient at discovery of abnormal
      finding, the rate of follow-up mammograms eventually requiring biopsy, the
      potential effects of tumor-doubling time on increasing the stage of disease,
      quality-of-life issues, and costs. RESULTS: For an average 50-year-old woman the
      quality-adjusted life expectancy (QALE) was longer for immediate biopsy by 0 to 3
      years, depending on the assumptions on tumor-doubling time; however, immediate
      biopsy increased the cost per patient from $700 to $900. The QALE was also
      superior for immediate biopsy if more than 30% of follow-up mammograms required
      biopsy, and immediate biopsy was more cost effective if more than 36% of follow
      up mammograms required biopsy. Patient age did not affect the superiority of
      immediate biopsy over observation, although quality-of-life issues did.
      CONCLUSIONS: Those lesions with a greater than 20% to 30% probability of being
      malignant, or lesions with potentially short doubling times, should undergo
      immediate biopsy. Lesions judged to be at lower risk may be observed for 6
      months. Either of these recommendations should be adjusted depending on an
      individual patient's quality-of-life concerns.

PMID- 7573724
TI  - Institution and per-surgeon volume versus survival outcome in Pennsylvania's
      trauma centers.
AB  - BACKGROUND: The American College of Surgeons recommends minimum patient volumes
      for trauma centers and surgeons. Those numbers, however, are largely based on
      results from studies of surgical (but not trauma) relationships between volume
      and outcome. METHODS: Using stepwise regression, relationships were sought
      between measures of patient volume per trauma center and per surgeon and ana
      severity-controlled measure of survival outcome (W). For significant z values, W
      is the number of additional (or fewer) survivors, per 100 patients treated, than
      expected from ASCOT norms. W = 0 when z is nonsignificant. Data are from patients
      admitted in 1988 and 1989 to accredited Pennsylvania trauma centers. RESULTS: The
      relationships found for all patients and for adult blunt-injured patients are W =
      0.3312 + 0.0200 (NSER/SURG) and W = 0.3638 + 0.0248 (NBSER/SURG), respectively,
      where NSER/SURG is the number of seriously, injured patients treated annually per
      surgeon and NBSER/SURG is the number of adult patients with serious blunt
      injuries treated annually per surgeon. Serious injury was defined, using the
      Injury Severity Scale, as > = 13 or, using the Abbreviated Injury Scale, as a
      head injury of > = 3. The relationships explained 36% and 61% of the variance in
      W (R2 for all patients and adult blunt-injured patients, respectively. To achieve
      normative survival (W =0), 95% confidence intervals suggest that a trauma surgeon
      should treat at least 35 seriously injured patients per year and at least 28
      adult patients with serious blunt injury annually. No volume-related variable was
      a significant contributor to predictions of W for adult patients with penetrating
      injuries or for pediatric patients. CONCLUSIONS: These results support the
      regionalization of trauma care by affirming that increased per-surgeon experience
      in the treatment of seriously injured patients is associated with improved
      outcomes and help define the minimum experience needed to achieve normative
      survival. Prospective study of the relationship between volume and survival and
      other outcomes is required.

PMID- 7573725
TI  - Penetrating trauma and emergency surgery in patients with AIDS.
AB  - BACKGROUND: Several recent publications have suggested that emergency surgery in
      patients with acquired immunodeficiency syndrome (AIDS) is associated with
      extremely high morbidity and mortality. PATIENTS AND METHODS: We reviewed the
      records of 21 patients with AIDS at the University of Miami/Jackson Memorial
      Medical Center in Miami, Florida, who underwent 24 emergency operations after
      sustaining penetrating trauma RESULTS: Nineteen patients (90%) presented with
      gunshot wounds and 2 (10%) presented with stab wounds. Two patients underwent
      multiple surgical procedures to control hemorrhage from a complex liver injury
      and to drain a retained hemothorax, respectively. After surgery, patients were
      managed according to standard protocols, the same as those for non-AIDS patients.
      Wound infection was present in 4 patients (19%), and occurred only in patients
      with < 100 CD4+ cells/microL. Fifty-seven percent of patients had no prior
      knowledge of having AIDS or being seropositive for the human immunodeficiency
      virus. One patient died after surgery and 18 patients (86%) were still alive 6
      months after discharge. CONCLUSIONS: As the AIDS epidemic grows, general surgeons
      will be treating an increasing number of these patients. A low morbidity and
      mortality can be obtained with standard surgical care and techniques.
      Complications are not uncommon and should be treated as in any other surgical
      patient, unless it is a terminal condition or that posture runs against the
      patient's stated views or advance directives.

PMID- 7573727
TI  - Preincisional single-dose ceftriaxone for the prophylaxis of surgical wound
      infection.
AB  - BACKGROUND: Preincisional intraparietal injection of antibiotics is used for the
      prophylaxis of postoperative surgical infections. Whether topically injected
      antibiotics remain primarily in the surgical wound or are systematically absorbed
      is uncertain, however. PATIENTS AND METHODS: The pharmacokinetics of
      preincisional injection of 2 g ceftriaxone were studied in 20 patients who have
      undergone abdominal surgery, with determination of serum, wound tissue, and wound
      fluid antibiotic concentrations. RESULTS: Preincisional injection of ceftriaxone
      resulted in high antibiotic concentrations in the wound tissue and wound fluid.
      The highest plasma concentrations were achieved at 1.50 hours (99.47 +/- 14.67
      micrograms/mL). Plasma concentrations exceeded the minimal inhibitory
      concentrations of most aerobic gram-positive and gram-negative organisms with the
      exception of Pseudomonas aeruginosa, Acinetobacter species, and Streptococcus
      faecalis for 24 hours (10.42 +/- 4.12). No local or general complications arose
      in any of the patients. CONCLUSIONS: Our results suggest that preincisional
      administration of ceftriaxone for prophylaxis is very effective.

PMID- 7573728
TI  - Treatment of choice for choledocholithiasis in patients with acute obstructive
      suppurative cholangitis and liver cirrhosis.
AB  - OBJECTIVE: To identify the treatment of choice for choledocholithiasis in
      patients with versus without acute obstructive suppurative cholangitis (AOSC) or
      liver cirrhosis, the outcomes of surgical treatment and endoscopic sphincterotomy
      (EST) were compared. PATIENTS AND METHODS: Three hundred sixty-two consecutive
      patients with choledocholithiasis were divided into three groups: 27 with AOSC
      (Group 1), 12 with cirrhosis (Group 2), and 323 with neither AOSC nor cirrhosis
      (Group 3). RESULTS: Seventeen patients (63%) in Group 1 underwent emergent
      treatment, and 3 of them died. Two were treated by emergency surgery and both
      died; only 1 (7%) of 15 treated by emergent EST died. For all patients with AOSC,
      morbidity and mortality rates were 67% and 33% with surgery, and 24% and 5% with
      EST. In Group 2, 2 patients with Child C cirrhosis died after elective EST. One
      patient in Group 3 died. Mortality rates were significantly higher in Group 1
      (11%) and Group 2 (17%) than in Group 3 (0.3%). Although comparisons between the
      two treatment approaches did not achieve statistical significance, EST had lower
      morbidity rates than surgery in both Group 1 (24% versus 67%) and Group 2 (22%
      versus 67%). The required hospital stay was half as long with EST as with
      surgery. CONCLUSIONS: EST is the recommended treatment for patients with
      choledocholithiasis associated with AOSC or liver cirrhosis.

PMID- 7573726
TI  - Isolated hyperthermic perfusion with mitoxantrone of melphalan in malignant
      melanoma of the limb.
AB  - BACKGROUND: Melphalan administered by isolated hyperthermic perfusion of the
      affected limb is an accepted treatment for malignant melanoma of the extremities.
      In contrast, pharmacologic and phase I studies suggest that, because of its high
      uptake, mitoxantrone may give even better local control, but data on survival,
      onset of metastases, and local and systemic toxicities have not yet been
      reported. METHODS: A matched-pairs comparison was performed to examine
      differences in the tolerability and effectiveness of isolated hyperthermic
      extremity perfusion with mitoxantrone (n = 44) and melphalan (n = 44) in high
      risk and locoregionally (P < 0.41) metastatic malignant melanoma. Criteria
      evaluated were local and systemic complications, and recurrence-free and overall
      survival. RESULTS: Local complications, such as delayed wound healing, were more
      frequent in the mitoxantrone (27.9%) than in the melphalan group (9.8%) (P <
      0.05). Systemic toxicity, in particular bone marrow toxicity, was also more
      severe with mitoxantrone (78.6% versus 15.4%, P < 0.001). Hepatotoxic effects
      were more frequent among patients in the melphalan group who were older and has
      lower tissue perfusion temperatures (P < 0.05). There was no difference between
      the two groups in overall or recurrence-free survival (P < 0.41). CONCLUSIONS:
      Local and systemic toxicity seem to be higher with mitoxantrone. Survival rates
      were similar with both drugs. The data obtained suggest a randomized phase II
      study with an appropriate number of patients.

PMID- 7573729
TI  - Factors predicting the recurrence of adhesive small-bowel obstruction.
AB  - BACKGROUND: A long-standing debate exists about whether stable patients who have
      adhesive small-bowel obstruction (ASBO) are best managed operatively or
      nonoperatively. In addition, the factors that predict recurrence have not been
      established. PATIENTS AND METHODS: We conducted a retrospective cohort study
      using medical records of 31 ASBO patients managed operatively and 59 managed
      nonoperatively. Follow-up data for up to 12.8 years after the index ASBO were
      collected from medical records. RESULTS: Life-table analyses found that ASBO
      recurred after 53% of initial episodes and 85% or more of second, third, or later
      episodes. Recurrence was much more rapid after third or later episodes than after
      first or second episodes. Recurrence occurred sooner and more frequently in
      patients managed nonoperatively than in patients managed operatively. These
      differences became statistically significant only after the second episode.
      CONCLUSIONS: The number of prior episodes is the strongest predictor of
      recurrence. The optimal management strategy is a function of the number of prior
      episodes a patient has experienced. Nonoperative management appears reasonable
      for stable patients who are having their first episode. Operative strategies
      appear best for those experiencing second episodes. Neither strategy yields
      acceptable outcomes in patients experiencing third or later episodes.

PMID- 7573732
TI  - Management of paraesophageal hernia with a selective approach to antireflux
      surgery.
AB  - BACKGROUND: The role of an antireflux procedure in the management of
      paraesophageal hernia is controversial. To address this issue, we reviewed our
      experience with selective use of antireflux procedures in patients with pure
      paraesophageal hernia (type II; n = 26) and those with a partial sliding
      component (type III; n = 11). PATIENTS AND METHODS: Surgical repair was performed
      on diagnosis in all 37 patients. Competency of the lower esophageal sphincter was
      evaluated on the basis of reflux symptoms, and objectively, with endoscopy in 21
      patients and 24-hour esophageal pH studies in 17 patients. Repair included an
      antireflux procedure in 11 patients, as indicated by reflux disease. RESULTS:
      Preoperatively, 80% of both type II and type III patients reported obstructive
      symptoms. Reflux symptoms were present in 27% of patients--19% of type II and 45%
      of type III patients. Endoscopy revealed esophagitis in 5 cases, and 24-hour pH
      studies indicated significant reflux in 3 of 17 patients. There were no operative
      deaths and 1 recurrence. Symptoms improved in 92% of patients after surgery.
      Medically manageable reflux was identified in 2 patients. CONCLUSIONS: Frequent
      obstructive symptoms and the potential for gastric volvulus indicate elective
      repair of paraesophageal hernia on diagnosis. Significant gastroesophageal reflux
      is less common, especially in type II patients, and excellent symptomatic results
      are obtained with selective application of an antireflux procedure.

PMID- 7573731
TI  - Patient-controlled analgesia and prolonged ileus after uncomplicated colectomy.
AB  - BACKGROUND: Because the duration of postoperative ileus after uncomplicated colon
      surgery has increased at our institution in the past 4 years, thereby prolonging
      length of hospital stay for some patients, we assessed several clinical factors
      to determine which were responsible for the increase. PATIENTS AND METHODS: We
      retrospectively studied a cohort of 358 patients who underwent uncomplicated
      colon resection to investigate risk factors for prolonged postoperative ileus.
      Postoperatively, all patients received an analgesic agent, delivered either
      intramuscularly (IM) or by patient-controlled analgesia (PCA) pump, until their
      postoperative ileus resolved, as indicated by the passage of flatus and tolerance
      of a clear liquid diet. RESULTS: There was no significant relationship between
      the length of postoperative ileus patient age or gender, the operating time, or
      the type or amount of analgesic agent used postoperatively. A significantly
      larger proportion of the patients who received PCA than those given an IM agent
      had ileus at 7, 6, and 5 days after surgery (P < 0.0001 for all comparisons after
      controlling for confounding factors), however. Overall, the use of PCA was
      associated with a delay in return of normal bowel function of 0.9 days. Patients
      who underwent a right colectomy had a significantly shorter ileus than those who
      had other procedures. CONCLUSIONS: Our findings indicate that the use of PCA
      after uncomplicated colectomy increases the risk of prolonged postoperative
      ileus. We suggest that the routine use of PCA after colon surgery be reevaluated.

PMID- 7573730
TI  - A prospective, randomized trial of short versus long tubes in adhesive small
      bowel obstruction.
AB  - BACKGROUND: Many cases of acute adhesive small-bowel obstruction (SBO) can be
      successfully treated with intestinal tube decompression. There is considerable
      controversy, however, regarding whether a short nasogastric tube (NGT) or a long
      nasointestinal tube (LT) is the best method of intestinal tube decompression.
      PATIENTS AND METHODS: A prospective, randomized trial was conducted to compare
      NGT and LT decompression with respect to the success of nonoperative treatment
      and morbidity of surgical intervention in 55 patients with acute adhesive SBO.
      RESULTS: Twenty-eight patients were managed with NGT and 27 with LT. There were
      44 cases of partial SBO (23 NGT, 21 LT) and 11 cases of complete SBO (5 NGT, 6
      LT). Twenty-one patients ultimately required operation, including 13 managed with
      NGT (46%) and 8 with LT (30%) (P = 0.16). The mean period between admission and
      operation was 60 hours in the NGT group versus 65 hours in the LT group. At
      operation, 3 patients in the NGT group had ischemic bowel that required
      resection. Postoperative complications occurred in 23% of patients treated with
      NGT versus 38% of patients treated with LT (P = 0.89). Postoperative ileus
      averaged 6.1 days for NGT patients versus 4.6 days for LT patients (P = 0.44).
      There were no deaths. CONCLUSIONS: Patients with adhesive SBO can safely be given
      a trial of tube decompression upon hospital admission. There was no advantage of
      one type of tube over the other in patients with adhesive SBO.

PMID- 7573733
TI  - Elimination of the Roux stasis syndrome using a new type of "uncut Roux" limb.
AB  - BACKGROUND: The Roux stasis syndrome, a syndrome of nausea, vomiting, abdominal
      pain, and postprandial fullness that follows Roux-en-Y gastrojejunostomy, is
      thought to result from the jejunal transection performed during the construction
      of a conventional Roux limb. The purpose of this study was to test a new type of
      "uncut" Roux limb construction, in which a neuromuscular bridge maintains
      neuromuscular continuity between the proximal jejunum and the Roux limb, while a
      jejunojejunostomy provides distal diversion of pancreaticobiliary secretions
      METHODS: After a distal hemigastrectomy, 5 dogs underwent the uncut Roux
      operation, while 5 others had a Billroth II reconstruction (controls). Three
      weeks later, recordings of jejunal myoelectrical activity and assessment of
      gastric emptying and bile reflux were performed in fully conscious dogs RESULTS:
      In the dogs with uncut Roux limbs, jejunal pacesetter potentials propagated
      aborally across the neuromuscular bridge, although their frequency was slightly
      slower distal to the bridge (proximal 19.5 +/- 0.7 cpm versus distal 18.8 +/- 1.1
      cpm; P < 0.05). No frequency change occurred across the comparable area of
      jejunum of the controls. Both groups had similar rates of gastric emptying. Only
      small amounts of bile acids were found in gastric aspirates from dogs with uncut
      Roux limbs. CONCLUSIONS: A new uncut Roux operation eliminated the Roux stasis
      syndrome by preserving neuromuscular continuity between the proximal jejunum and
      the Roux limb, and yet provided near-total diversion of bile from the gastric
      remnant.

PMID- 7573734
TI  - Factors influencing wound dehiscence after midline laparotomy.
AB  - PURPOSE: To identify patients who have high risk of wound dehiscence and who
      might benefit from the use of internal retention sutures. PATIENTS AND METHODS:
      Forty-eight patients with midline abdominal wound dehiscence were compared with
      48 control patients standardized by sex, age, and operative indication. RESULTS:
      The mean hospital stay was significantly prolonged in the dehiscence group,
      resulting in a higher total cost of hospital treatment. The variables that were
      significantly associated with wound dehiscence included hypoalbuminemia, anemia,
      malnutrition, chronic lung disease, and emergency procedure. The additional
      postoperative factors that were found to be significant were vomiting, prolonged
      intestinal paralysis, repeated urinary retention, and increased coughing.
      Obesity, chronic heart disease, diabetes, alcoholism, preoperative intestinal
      obstruction, jaundice, systemic and local infection, use of steroids, type of
      incision, operating time, and type of wound closure were nonsignificant
      variables. The number of wound dehiscences increased significantly (P = 0.0001)
      when the number of risk factors increased from zero to five. CONCLUSION: We
      recommend using internal retention sutures for patients who have three or more
      risk factors.

PMID- 7573736
TI  - Hemodynamic effects of intermittent pneumatic compression of the lower limbs
      during laparoscopic cholecystectomy.
AB  - BACKGROUND: The effects of surgical pneumoperitoneum on lower-limb venous
      hemodynamics have already been studied; however, the effects of intermittent
      compression boots are not known in such venous-stasis conditions. METHODS: In 12
      volunteers and 12 patients, the venous hemodynamic effects of intermittent leg
      compression were studied under external abdominal pressure or during laparoscopic
      cholecystectomy, respectively. Femoral venous diameter and velocity were
      measured. Venous pressure was monitored during the surgical procedures. RESULTS:
      External abdominal pressure of 50 mm Hg and pneumoperitoneum were found to
      increase the diameter (17% in the volunteers and 14% in the patients) and
      decrease peak velocity (49% and 32%, respectively) in the femoral vein. Femoral
      pressure was increased (106%) during pneumoperitoneum. In both venous-stasis
      circumstances, intermittent compression of the legs restored venous flow
      velocity, but had no effect on vessel diameter and pressure. CONCLUSIONS: The
      lower-limb venous hemodynamic changes were similar during external abdominal
      pressure or pneumoperitoneum, and the flow velocity decrease was intermittently
      reversed by pneumatic compression boots.

PMID- 7573735
TI  - Extracorporeal pneumoperitoneum access bubble for endoscopic surgery.
AB  - The extracorporeal pneumoperitoneum access bubble (EPAB) creates a transparent
      extension of the pneumoperitoneum and has been developed to facilitate large
      organ extraction and tissue approximation in patients undergoing endoscopic
      surgical procedures. When fully deployed, the EPAB excludes the abdominal
      parietes from the emergent organ and dilates the exit wound by an average of
      48.5%, irrespective of its location. It thus eliminates the problems of
      contamination and tumor seedling implantation during the removal of resected
      organs, aside from expediting the extraction. The operating version of the EPAB
      enables the introduction of the surgeon's or assistant's hands or instruments
      into the bubble and thence into the peritoneal cavity without deflation of the
      pneumoperitoneum. By this means, it reduces the technical difficulties required
      to dissect organs and achieve reconstruction by hand suturing or stapling.

PMID- 7573739
TI  - Ethanol diffusion miscalculation.

PMID- 7573738
TI  - The diagnosis and management of breast problems during pregnancy and lactation.
AB  - BACKGROUND: In addition to mastitis, lactational breast abscesses, and several
      other benign conditions unique to the puerperium, pregnant women may develop any
      of the other breast problems seen in the nonpregnant female population. This
      review deals with the diagnosis and management of breast problems during
      pregnancy and lactation. DATA SOURCES: A literature review of the evaluation,
      technique of biopsy, and treatment of cancer in pregnant women was conducted.
      CONCLUSIONS: The most common problems fall into a spectrum of infectious
      complications from milk stasis or mastitis to frank abscess formation.
      Galactoceles, noninfected milk-filled cysts, present as tender masses; aspiration
      is both diagnostic and curative. Benign fibroadenomas occasionally enlarge
      significantly or infarct during pregnancy. A physiologic nipple discharge is
      common during pregnancy, and may be bloody. Rare cases of massive breast
      hypertrophy during pregnancy have been reported. The mortality of breast cancer
      during pregnancy is related to delay: compared stage-for-stage with nonpregnant
      controls, the prognosis is similar. As a general rule, the cancer should be
      treated surgically and the pregnancy may be allowed to progress.

PMID- 7573740
TI  - Laparoscopic onlay versus conventional inguinal herniorrhaphy.

PMID- 7573737
TI  - Clamp control of the right ventricular angle to facilitate exposure and repair of
      cardiac wounds.
AB  - Penetrating cardiac wounds, especially those of the posterior surface, present a
      major challenge to the trauma surgeon. Previously described methods to assist in
      cardiac exposure include manual control and apex stitch. The authors describe a
      simple technique to facilitate exposure during acute control and repair of
      traumatic cardiac wounds. Using an atraumatic vascular clamp in the fashion
      described allows for improved exposure and easier repair of heart surface wounds.

PMID- 7573742
TI  - High levels of fibronectin in the stroma of aural cholesteatoma.
AB  - PURPOSE: Because abundant fibronectin deposition is a hallmark of healing
      cutaneous wounds and provides a matrix for hyperproliferative and migratory
      epidermal cells, the distribution of fibronectin in aural cholesteatoma was
      investigated immunohistochemically. MATERIALS AND METHODS: A monoclonal antibody
      against the major cell binding domain of human fibronectin was used to stain 4
      micron cryosections of cholesteatoma tissue by the alkaline phospatase
      antialkaline phosphatase method. Section of normal retroauricular skin served as
      control. RESULTS: When processed in parallel, fibronectin staining was much
      stronger in the stroma of cholesteatoma than in normal dermis. The squamous
      epithelium of both tissues did not show any staining for fibronectin.
      CONCLUSIONS: These observations lend support to the view that the growth of
      cholesteatoma epithelium reflects an aberrant regenerative process.

PMID- 7573741
TI  - Management of delirium tremens on the head and neck service.

PMID- 7573743
TI  - Bleomycin sclerotherapy in patients with congenital lymphatic malformation in the
      head and neck.
AB  - Congenital lymphatic malformations of the head and neck often present challenging
      problems to the otolaryngologist-head and neck surgeon. Although surgical
      excision was agreed to be the treatment of choice for this disease, the
      infiltrating nature of lymphatic channels often increases the frequency of
      operative complications and recurrences of this lesion. PURPOSE: Bleomycin
      sclerotherapy was attempted to avoid surgical risk and to cure this lesion.
      MATERIALS AND METHODS: Clinical findings and treatment results were reviewed for
      patients with congenital lymphatic malformation and treated by bleomycin
      sclerotherapy. RESULTS: Bleomycin sclerotherapy was a very effective therapeutic
      alternative. The best results were seen in cystic type 1 lesions in younger
      patients. CONCLUSIONS: Bleomycin sclerotherapy is a useful medical alternative,
      and we believe that it should be attempted before excision of the lesion.

PMID- 7573745
TI  - Magnetic resonance imaging features of Gradenigo's syndrome.

PMID- 7573746
TI  - Intranasal schwannoma: magnetic resonance and computed tomography appearance.

PMID- 7573748
TI  - Internal jugular vein reconstruction in bilateral radical neck dissection.

PMID- 7573747
TI  - Epistaxis from nontraumatic intracavernous carotid aneurysm: endovascular
      treatment with detachable coils and electrothrombosis.

PMID- 7573749
TI  - Primary cutaneous mucormycosis.

PMID- 7573750
TI  - Case of thromboangiitis obliterans (Buerger's disease) of the upper lip.

PMID- 7573751
TI  - Head and neck manifestations of Maffucci's syndrome: chondrosarcoma of the nasal
      septum.
AB  - The possibility of a dyschondroplastic syndrome should be considered in any
      patient presenting with a cartilagenous tumor in the head and neck.
      Classification of the patient as Maffucci's syndrome or Ollier's disease
      increases the need for vigilant observation for the development of sarcomatous
      lesions and can help differentiate between low-grade chondrosarcoma and atypical
      enchondroma.

PMID- 7573744
TI  - CUSUM analysis of the SCC antigen in patients with head and neck cancer.
AB  - PURPOSE: Serial postoperative serum squamous cell carcinoma antigen (SCCAg)
      levels in a group of head and neck cancer patients were evaluated using a
      cumulative sum (CUSUM) technique to determine the prognostic value of serial
      SCCAg levels in predicting tumor recurrence. MATERIALS AND METHODS: A
      retrospective analysis of serial postoperative SCCAg measurements in 75 patients
      with squamous cell carcinoma of the head and neck (SCCHN) from two previous
      studies of SCCAg was performed. Serum SCCAg levels were determined by
      radioimmunoassay. A V-mask was used to detect significant deviations of greater
      than 1 SD of the CUSUM from the reference value. SETTING: Oncologic head and neck
      practice at a tertiary referral hospital. PATIENTS OR OTHER PARTICIPANTS: Seventy
      five consecutive patients with a minimum of three postoperative SCCAg
      determinations were reviewed to provide equal numbers with and without recurrent
      disease. All patients who remained disease-free were followed for a minimum of 2
      years. All patients were previously untreated and underwent surgical therapy.
      MAIN OUTCOME MEASURES: CUSUM curve of postoperative SCCAg levels and 2-year
      disease-free survival. RESULTS: In a group of 38 patients with 2-year disease
      free survival, the CUSUM analysis did not detect any significant deviation in
      postoperative SCCAg levels for up to 23 months after surgery. In a group of 37
      patients who subsequently died of disease, a deviation of greater than 1 SD was
      noted as early as 5 months postoperatively and persisted throughout the course of
      their monitoring for up to 36 months. CONCLUSIONS: The CUSUM technique is more
      sensitive for detecting postoperative changes in serial measurements of the SCCAg
      and may be applicable to the monitoring of individual patients for recurrent
      disease.

PMID- 7573752
TI  - An endoscopic approach to metallic foreign bodies of the nose and paranasal
      sinuses.

PMID- 7573753
TI  - Proliferative events in the cerebral ventricular zone.
AB  - The neocortex varies vastly in size and complexity yet its cytology, laminar
      architecture, and general plan of cytoarchitectonic organization are closely
      similar across mammalian species. These similarities of structure and
      organization emerge in the course of a closely similarly developmental history.
      Thus, the neocortex in all species arises in the course of a discrete
      neuronogenetic interval (NI) from a pseudostratified ventricular epithelium (PVE)
      located in the margin of the developing cerebral wall. Once their terminal cell
      division in this epithelium has been completed the young neurons migrate across
      the cerebral wall to the neocortex where they grow, differentiate, and become
      synaptically incorporated into cerebral neural systems. The neurons forming the
      deepest cortical layers are the earliest to be formed while progressively later
      formed neurons arise at progressively later times in development. In experiments
      in mice, we have determined that it is the relation of total cell cycle number,
      occurring in the course of the NI, to the cell cycle output function, Q, which is
      regulatory to the duration of NI and to the rate of neuron production. Cell cycle
      number appears largely to be regulated by progression in the length of the G1
      phase of the cycle. We propose that regulation is mediated by cell external
      substances, acting upon the proliferating cell during G1 phase.

PMID- 7573754
TI  - Periventricular hemorrhage in a developing world. Is drug intervention
      appropriate?
AB  - This study examined the factors associated with the development of
      periventricular hemorrhage (PVH) in black low-birth weight infants from a
      disadvantaged community. In addition, the use of drugs as a preventive strategy
      for the development of PVH was addressed. A total of 177 babies weighing less
      than 1.5 kg were studied. Eighty (45.2%) were found to have PVH. Grade I PVH was
      diagnosed in 33 (41.3%), grade II in 37 (46.3%) and grade III in 10 (12.4%) of
      the babies studied. The overall mortality was 32% (57/177). Mortality of babies
      with grade I was 33% (11/33), grade II 63% (22/35) and 70% (7/10) for grade III.
      In those with normal scans the mortality was 18% (17/96). Babies with a lower
      weight had the severer grade of PVH (P < 0.05). Univariate analyses suggested
      that lower weight and gestational age, mode of delivery, asphyxia, RDS, shock,
      hypothermia and the need to administer plasma were the risk factors for both
      mortality and PVH. However, multiple logistic regression analysis revealed that
      lower weight (P < 0.001, RR 6.135), asphyxia (P < 0.0004, RR 6.849) and the
      administration of plasma (P < 0.0026, RR 6.024) were the major factors
      contributing to death. For the development of PVH weight (P < 0.0001, RR3.719)
      and the need for plasma (P < 0.03,RR2.079) were crucial. Obstetric complications,
      place of delivery and booking status did not play a significant role in PVH. The
      findings in this study suggest that drug intervention in the future may not be
      appropriate and should be considered when care of the small baby has improved.

PMID- 7573755
TI  - EEG features and epilepsy in patients with autism.
AB  - Epileptic seizures are frequently reported (4-32%) in autism. These values are
      higher than in the normal population of children and adolescents (0.5%). In the
      literature there is no uniform description of epilepsy in autism. We examined 106
      patients with autistic disorder divided into three groups on the basis of
      presence or absence of EEG paroxysmal abnormalities (PA) and / or epilepsy
      including febrile convulsions (FG). Our patients presented an autistic syndrome
      unrelated to clear congenital or acquired encephalopathy. The prevalence of
      epilepsy and EEG PA was 23.6% and 18.9%, respectively. Significant differences
      between the three groups appeared for (i) familial antecedents for epilepsy / FC
      and neurologic and psychiatric diseases (P < 0.004), (ii) a different proportion
      between the three groups for mental retardation (P < 0.03), (iii) and EEG fast
      activity (P < 0.04). Our patients showed several types of epilepsy, including
      idiopathic forms with seizure onset after the age of 10 in 45% of cases. Seizures
      were mainly partial, not frequent and controllable by anti-epileptic drugs. PA
      were mostly focal and multifocal and in 45% of cases were typical of benign
      childhood partial epilepsy with centro-temporal spikes. The higher incidence of
      epilepsy and EEG PA is apparently not related to organic pre-, peri- and
      postnatal antecedents or cerebral lesions. On the contrary, genetic factors
      responsible for autism and epilepsy seem important in the genesis of these two
      disorders.

PMID- 7573756
TI  - Neurophysiological study in Pelizaeus-Merzbacher disease.
AB  - The Neurophysiological characteristics of Pelizaeus-Marzbacher disease (PMD) were
      studied in four Japanese patients aged between 5 and 13 years. Pendular
      spontaneous nystagmus was always recorded with a frequency between 2.5 and 4 Hz,
      and abnormal saccades with an almost twofold prolongation in onset time and 50%
      decrease in velocity were noted. Brainstem auditory evoked potentials
      consistently demonstrated severely altered waves II to V, following a normal wave
      I, despite normal hearing acuity. Somatosensory evoked potentials (SEPs) were
      always absent between brainstem components and early cortical responses. Late
      cortical components of SEPs and visual evoked potentials with significantly
      prolonged latencies were recorded in the three younger cases having normal
      sensory and visual acuity (N35 of SEP, 73.1 +/- 2.1 ms; N75 of VEP, 129.0 +/-
      12.7 ms; mean +/- S.D.), while these peaks were absent in the oldest case having
      the most severe handicap. In motor evoked potentials (MEPs), R1 of blink reflex
      with significantly prolonged latency (14.9 +/- 1.48ms) was always obtained, and
      no subsequent R2 was elicited. Magnetic transcortical stimulation elicited no
      MEPs of the thenar even in the facilitating condition on voluntary contraction
      despite mild weakness of the thenar, while normal MEPs were always elicited on
      cervical stimulation. These electrophysiological findings were consistent with
      extensive conduction slowing involving the brainstem to the cerebrum, which
      seemed to be accompanied by conduction block in motor systems rather than sensory
      systems. Although each of the results was not specific, in combination they
      suggested the characteristics of diffuse brain dysmyelination in PMD.

PMID- 7573757
TI  - Drug interactions of zonisamide with phenytoin and sodium valproate: serum
      concentrations and protein binding.
AB  - The influence of co-medication with zonisamide (ZNS) on the serum concentration
      and protein binding of phenytoin (PHT) and sodium valproate (VPA) was studied in
      21 pediatric patients. No significant correlation between the daily ZNS dose, and
      total serum concentrations, free concentrations or free fractions (FF) of PHT or
      VPA was observed. The patient study showed that changes in the FF of PHT and VPA
      were correlated more closely with the serum protein and bilirubin levels than
      changes in the ZNS dosage. An in vitro study revealed that the addition of ZNS
      caused decreases in the FF of PHT and VPA. However, these decreases were within
      the range of measurement error and were negligible. In conclusion, no significant
      effect of ZNS on the serum concentration or protein binding of PHT or VPA was
      demonstrated.

PMID- 7573758
TI  - Preventive effects of dexamethasone on hypoxic-ischemic brain damage in the
      neonatal rat.
AB  - To clarify the preventive effects of glucocorticoid on perinatal hypoxic-ischemic
      (HI) brain damage, an experiment was carried out on 4-day-old rats pretreated for
      4 consecutive days with 3 different regimens; namely, a low dose dexamethasone
      (Dex) (0.1 mg/kg/day), a high dose Dex (0.5mg/kg/day), and a saline
      administration. On the 7th postnatal day, after ligation of the left common
      carotid artery, the rats were exposed to 8% oxygen and decapitated on the 10th,
      14th, 21st and 28th postnatal days. Ligated side brain damage was observed in 75,
      7 and 3% of the rats in the saline, low and high dose Dex groups, respectively.
      However, a high mortality rate (42%) was noted in the high dose Dex group. The
      cumulative number of animals with poor outcome (death or brain damage) was 49
      (80%), 13 (33%) and 24 (44%) in the saline, low and high dose Dex groups,
      respectively. On the 10th and 14th postnatal days, the rats in both the Dex
      groups showed delayed neuronal maturation and myelination in the non-ligated side
      motor cortex, however, these maturational differences disappeared on the 21st
      postnatal days. Otherwise, the number of cortical cells in both the Dex groups
      were significantly lower than that in the saline group on the 28th postnatal days
      (P < 0.05 in each). These findings suggest that the pretreatment with Dex
      protects the developing brain from HI injury through the suppression of the
      neuronal maturation. However, a decreased number of cortical cells may give rise
      to psychomotor retardation later.

PMID- 7573759
TI  - Bilateral opercular syndrome: an unusual complication of perinatal difficulties.
AB  - We describe an 8-year old boy with pseudobulbar palsy and speech disturbance
      associated with fetal distress, mild birth asphyxia and probably intracranial
      hemorrhage. There is a remarkable dissociation between orofacial voluntary
      movements and emotional expression. MRI revealed cortical atrophy and subcortical
      gliosis of both opercula. The clinical and neuroradiological features correspond
      to bilateral opercular syndrome. We assume that a reduction of cerebral blood
      flow involving both opercula induced pseudobulbar palsy with severe expressive
      speech disturbance.

PMID- 7573760
TI  - Basal encephaloceles with morning glory syndrome, and progressive hormonal and
      visual disturbances: case report and review of the literature.
AB  - We report an 11-year-old girl with progressive hypopituitarism and visual loss of
      the right eye caused by trans-sphenoidal and sphenoethmoidal encephaloceles
      associated with morning glory syndrome. She was first seen at the age of 8 years,
      because of polydipsia and polyuria, and examination at that time revealed
      pituitary dwarfism and morning glory syndrome with visual disturbance of the
      right eye. Hormonal examinations revealed deficiency of growth hormone (GH) and
      anti-diuretic hormone (ADH). MR image showed trans-sphenoidal and sphenoethmoidal
      encephaloceles. At the age of 9 years, she was found at another institution to be
      blind in the right eye. Our examination of the patient at the age of 11 years
      revealed no change of the findings for the encephaloceles or optic system.
      Hormonal examination disclosed deficiencies of all hormones except for
      thyrotropin (TSH). This patient showed progressive hormonal and optic
      disturbances during the follow-up period. The natural course is still unclear,
      but our review of reported cases of trans-sphenoidal encephalocele with hormonal
      disturbance revealed that the most frequent findings were GH and ADH disturbance
      (over 60%), most patients (77.8%) showed progression of hormonal disturbance, and
      40% of those with optic dysfunction showed progression. A patient with basal
      encephalocele with hormonal and / or optic disturbances requires careful long
      term follow up.

PMID- 7573761
TI  - A carrier of Duchenne muscular dystrophy with dilated cardiomyopathy but no
      skeletal muscle symptom.
AB  - A 29-year-old female developed dilated cardiomyopathy at 20 years of age but with
      no muscle symptoms. Her 2-year-old son with Duchenne muscular dystrophy (DMD)_had
      no demonstrable deletion in the dystrophin gene, but all fibers except for 5%
      'revertant' fibers in a muscle biopsy specimen had no dystrophin. Both skeletal
      and cardiac muscle biopsy specimens from the mother showed a mosaic distribution
      of dystrophin-positive and -negative fibers, and so she was diagnosed as being a
      manifesting carrier of DMD. We conclude that, when one encounters a female
      patient with idiopathic cardiomyopathy with a high serum creatine kinase level,
      the suspicion of her being a manifesting DMD carrier should be ruled out.

PMID- 7573762
TI  - Early onset distal muscular dystrophy.
AB  - A 14-year-old Chinese boy, who first became aware of muscle weakness in the lower
      limbs at 6 years of age, had progressive distal muscle weakness and atrophy,
      predominantly in the lower leg muscles. He exhibited reduced ankle dorsiflexion
      and tended to walk on his toes, showing preferential anterior tibial muscle
      involvement. Laboratory examination revealed a moderately elevated serum creatine
      kinase level of 905 IU/l. Computed tomographic scanning of muscle disclosed low
      density areas in the lower legs. A muscle biopsy specimen from the biceps brachii
      revealed mild dystrophic changes. We made a diagnosis of distal muscular
      dystrophy based on these findings, but could not classify it as one of the
      previously reported forms. The symptoms mimicked those of tibial muscular
      dystrophy, though the onset of the disease is far earlier than the previously
      described ones of distal muscular dystrophies. It remains unknown whether this
      patient has a new type of distal muscular dystrophy, or a variant form of the
      Miyoshi type or tibial muscular dystrophy.

PMID- 7573763
TI  - A case of dyskinetic cerebral palsy resembling post-anoxic action myoclonus.
AB  - Myoclonus after brain anoxia is more commonly observed in adults. Perinatal
      anoxia, however, on rare occasions causes myoclonus as the main neurologic
      abnormality. In this paper we described a case of cerebral palsy complicated by
      chorea and tremulous movements of the foot in which there were no risk factors
      except perinatal asphyxia. The patient had unique symptoms, action myoclonus
      associated with the movements of hyperkinesie volitionnelle. This case
      illustrated two points. One is that abnormal involuntary movements attributed to
      perinatal brain insults had changed as the brain matured. The other is that some
      movements were very similar to those of the post-anoxic action myoclonus,
      commonly seen in patients who sustain brain damage in adulthood.

PMID- 7573765
TI  - Tolosa-Hunt syndrome with pseudotumor cerebri. Report of an unusual case.
AB  - An 12-old-year girl with Tolosa-Hunt syndrome (THS) complicated with pseudotumor
      cerebri is presented. She suffered from alternating, recurrent and painful
      ophthalmoplegia at the age of 8, and bilateral papilledema which did not affect
      visual acuity was also recognized. THS subsided readily on steroid therapy, and
      the remission lasted more than 3 years after discontinuing steroid. However,
      papilledema did not change despite remission of THS, and resulted in optic
      atrophy with a mildly enlarged scotoma and 10% decrease in visual acuity 6 months
      after the onset. MRI disclosed slightly contrasted masses in the bilateral
      enlarged cavernous sinuses and narrowing of the left carotid siphon. Another
      small mass with partial gadolinium enhancement was revealed adjacent to the left
      narrowing of the carotid siphon in the optochiasmatic cistern; however, there was
      no lesion causing intracranial hypertension. The intracavernous MRI findings were
      considered characteristic of THS, and papilledema seemed to be due to pseudotumor
      cerebri by exclusion. Since subsequent MRI confirmed no progression of the above
      findings, the intracavernous and intracisternal masses were suspected to be non
      specific inflammatory granulomas associated with THS.

PMID- 7573764
TI  - Clozapine for tardive dyskinesia in adolescents.
AB  - Thousands of adolescents use neuroleptic drugs over extended periods of time for
      a wide range of mental disorders. One of the most severe adverse effects of
      neuroleptic drugs is tardive dyskinesia (TD), for which no successful treatment
      is currently available. Clozapine is a known atypical neuroleptic drug with few
      extrapyramidal side effects. It has been suggested that clozapine may be
      beneficial for the treatment of tardive dyskinesia in adolescents. However, the
      efficacy of the drug in adolescents is unknown. This report describes the
      beneficial effect of clozapine on tardive dyskinesia in two adolescents with
      schizophrenia.

PMID- 7573767
TI  - Is carbamazepine associated with NAG elevations suggestive of renal disease?
AB  - Elevations of urinary N-acetyl-beta-glucosaminidase (NAG) were found in previous
      studies of epileptic patients using carbamazepine. Since NAG can be a sensitive
      indicator of urinary tract problems, it was postulated that carbamazepine could
      be causing urinary tract damage. To explore this issue further, 27 mood disorder
      patients who were taking carbamazepine were compared to 171 mood disorder
      patients who were not using carbamazepine. There were no significant differences
      in NAG levels between the two groups. A hypothesis is presented which states that
      the elevated NAG levels found in some seizure patients could be associated with
      abnormalities of serotonin metabolism.

PMID- 7573766
TI  - Pancreatitis with normal serum amylase associated with sodium valproate: a case
      report.
AB  - The patient was a 1-year-old infant with severe postencephalitis syndrome.
      Diarrhea and elevation of the pancreatic enzymes, except for serum amylase
      (elastase 1 > 1, 5000 ng/dl (100-400); lipase, 885 IU/I/37 degrees C (10-48);
      trypsin, > 900 ng/ml (110-460)), were observed starting 70 days after starting
      valproate (dose, 70 mg/kg; serum level, 83.8 micrograms/ml). These findings as
      well as those obtained by abdominal ultrasonography suggested a diagnosis of
      pancreatitis, which was thought to be caused by sodium valproate. Important signs
      of valproate-induced pancreatitis may be easily overlooked in patients with
      neurological impairment, such as in ours. Because the blood half-life of amylase
      is short, not only amylase but some other pancreatic enzymes should be promptly
      investigated when valproate-related pancreatitis is clinically suspected in
      physically or mentally handicapped children.

PMID- 7573768
TI  - Neuronal ceroid-lipofuscinosis: late infantile form or juvenile form?

PMID- 7573769
TI  - 3-Methylglutaconic aciduria, type 3.

PMID- 7573772
TI  - Fetal alcohol and thymocyte phenotypes in offspring: response to food
      deprivation.
AB  - Restriction of food availability is a reliable stimulus that leads to significant
      hypothalamo-pituitary-adrenal (HPA) activation to which rats do not habituate.
      Based on our previous data that indicated that the HPA response to some, but not
      all, stressful stimuli is significantly greater in adult offspring of Sprague
      Dawley dams exposed to 35% alcohol during the last 2 weeks of gestation than that
      of control rats and on the mounting neuroendocrine-immune literature that
      describes the role of pituitary-adrenal products in modulating cellular immunity,
      we hypothesized that the outcomes of food restriction would be significantly more
      marked in fetal alcohol-exposed (FAE) offspring, compared with control rats. Data
      we report herein show that--whereas food restriction at 30-35 days of age
      produced significant changes in body weight, thymus weight-to-body weight ratio,
      adrenal weight-to-body weight ratio, plasma corticosterone levels, and in
      thymocyte number, as well as in the percentage and absolute number of CD4+ and
      CD8+ thymocytes that express CD45RC-FAE and control rats were equally affected.
      We conclude that food restriction is another example of a stressful stimulus that
      fails to distinguish satisfactorily between FAE and control rats of prepubertal
      age.

PMID- 7573770
TI  - Introduction to the symposium on alcohol and T-cell immunity.

PMID- 7573771
TI  - Alcohol modulation of human normal T-cell activation, maturation, and migration.
AB  - We are interested in the characterization of the effects of alcohol on human T
      cell activation, maturation, and migration, because this cell population is
      crucial in the initiation, regulation, and propagation of cellular immunity. We
      and others have described the effects of both acute and chronic exposure of human
      immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports
      and expand this body of literature with the inclusion of new data recently
      obtained in our laboratory. We confirm the blunting effects of EtOH on the
      production of interleukin-2 and mitogen proliferative response following T-cell
      mitogen stimulation, and on the expression of membrane markers of activation. We
      show that EtOH significantly alters the expression of the CD4 cell-associated
      marker of activation, CD26. We report the effect of EtOH on the expression of the
      homing receptor CD62L by CD4+ cells, and on their ability to adhere by a CD18
      mediated process to a defined cellular substratum. Furthermore, we demonstrate
      the effects of EtOH and EtOH and beta-endorphin pretreatment on the activation of
      CD4+ lymphocytes endowed with the homing receptor CD62L.

PMID- 7573773
TI  - Alcohol modulation of immune function: clinical and experimental data. Veterans
      Affairs Cooperative Study Groups 119 and 275.
AB  - In both animal and human studies, ethanol seems to modulate host immune function.
      In a variety of animal studies, ethanol has been shown to decrease lymphocyte
      function and number. In human studies of patients with alcoholic hepatitis, these
      abnormalities were also seen with specific correlation with protein malnutrition.
      Hepatic pathological lesions were also correlated with lymphocyte subset
      infiltration. However, peripheral blood lymphocytes did not correlate
      consistently with hepatic histopathology.

PMID- 7573774
TI  - Modulation of T-cell adhesion markers, and the CD45R and CD57 antigens in human
      alcoholics.
AB  - Direct and indirect evidence indicates that T cells are altered in alcoholics.
      The most commonly reported changes under direct examination have been consistent
      with an increased level of activation as reflected by shifts in the ratio of
      common leukocyte antigen isoforms expressed at the cell surface, by increases in
      the expression of class II antigen, or by alterations in the expression of
      various adhesion molecules. Functional evidence for T-cell abnormality includes
      loss of delayed hypersensitivity and a number of findings attributed to
      dysregulation of B cells by alcoholic T cells; these include the widely reported
      distrubances of immunoglobulin production in vivo and a range of abnormal
      responses when T and B cells are combined in vitro. Detailed flow cytometric
      examination of T cells from alcoholics with or without active liver disease
      reveals a significant loss of L-selectin CD8+ T cells, but not usually of CD4+ T
      cells. There is an inverse increase in the expression of CD11b on the CD8+ cells
      that have decreased L-selectin+ percentages. Both CD8+ and CD4+ T cells in
      alcoholics display a significant loss of the CD45RA isoform and a gain of cells
      exhibiting the CD45RO isoform. Other surface alterations include increased
      expression of CD57, a marker most commonly associated on T cells with conditions
      of chronic increased antigenic exposure. It is argued that these and other T-cell
      alterations in alcoholics are cytokine-driven in part and result in T-cell
      differentiation states that are functionally inappropriate.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7573775
TI  - CYP2E1 and ALDH2 genotypes and alcohol dependence in Japanese.
AB  - The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and
      nonalcoholic (healthy) Japanese were investigated to examine the relationship
      between the polymorphism of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the
      susceptibility to alcoholism. There was no significant difference in C2 gene
      frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas
      there was a significant difference in ALDH2 allele frequency, suggesting that, in
      Japanese, the C2 genotype of CYP2E1 may have nothing to do with the risk of
      developing alcohol dependence. However, the ALDH2*1 allele may influence drinking
      behavior and the development of alcohol dependence. Furthermore, racial
      interethnic differences in the frequency of the mutated allele of the CYP2E1 gene
      (C2) were found, like the ALDH2 gene. Japanese healthy controls showed a
      significantly higher frequency of the C2 allele than did Swedish healthy controls
      (0.05; reported by Persson et al., FEBS Lett. 319:207-211, 1993).

PMID- 7573776
TI  - Event-related potentials in alcoholic men, their high-risk male relatives, and
      low-risk male controls.
AB  - A total of 217 adult male subjects were evaluated utilizing event-related
      potentials (ERPs) elicited with two different auditory tasks (Counting and Choice
      Reaction). Ninety-eight alcoholics from high-density, multigenerational families
      were evaluated along with 39 first-degree nonalcoholic relatives from the same
      high-density families. Eighty controls, selected for low density of alcoholism in
      their extended families, were also studied. Using both conventional and
      topographic analyses, no significant differences in the amplitude of the P300
      component could be found with either of the auditory tasks. No significant
      differences in amplitude of N250 were seen. The latency of N250 increased with
      increasing conditional probabilities (0.33, 0.67, and 1.00), a trend that was
      amplified in the Counting task as compared with the Choice Reaction task. This
      prolongation in a task not requiring a reaction response (button press) tended to
      increase the latency more for alcoholics than controls or high-risk nonalcoholic
      subjects. Age, lifetime, and recent drinking were treated as covariates in all
      analyses. The absence of P300 amplitude differences between adult high- and low
      risk subjects is discussed in the context of the much more reliable differences
      seen between high- and low-risk children from the same high- and low-density
      families, when evaluated with the same auditory tasks.

PMID- 7573777
TI  - Behavioral dysfunction and cognitive efficiency in male and female alcoholics.
AB  - This study was conducted to examine the role of childhood behavioral disorders
      (CBDs) and residual attention deficit disorder (ADDRT) in alcohol-related
      cognitive dysfunction in male and female subjects. Alcoholic (n = 44 females, 56
      males) and control (n = 40 females, 40 males) subjects completed assessments that
      included measures of CBDs, ADDRT, and cognitive and psychosocial functioning.
      Cognitive tests were specifically designed to assess efficiency in function. As
      expected, alcoholics were inferior to controls in their cognitive efficiency
      [F(1,171) = 10.43, p = 0.0015]. Alcoholics reported more CBDs [F(1,161) = 12.02,
      p = 0.0007], regardless of sex. They also reported more ADDRT [F(1,173) = 44.12,
      p = 0.0001] than did controls. There were also sex [F(1,173) = 13.31, p = 0.0004]
      and group by sex effects [F(1,173) = 3.93, p = 0.05]. Female alcoholics reported
      more ADDRT symptoms than any other group. Regression equations conducted to
      clarify the relation between group, sex, CBDs, ADDRT, and cognitive efficiency
      indicated that the best predictor of cognitive efficiency was group
      classification (alcoholic versus control). That is, although symptoms of
      behavioral disorders were reported significantly more frequently by both male and
      female alcoholic subjects, these symptoms could not account for the cognitive
      impairment observed in either sex.

PMID- 7573778
TI  - Is alcohol-related flushing a protective factor for alcoholism in Caucasians?
AB  - Although alcohol-related flushing seems to be a genetically influenced protective
      factor for alcoholism in some Asian groups, little is known about whether this is
      true for Caucasians. The evidence for alcohol-related flushing as a protective
      factor for the development of alcoholism was examined in a sample of 5831
      Australian twins (2041 men, 3790 women) who were administered a structured
      psychiatric interview. Twin correlations for self-reported adverse alcohol
      reactions (e.g., "flushing or blushing" and "feeling very sleepy" after drinking
      1 or 2 drinks) were modest, suggesting minimal contribution of genetic factors,
      but when corrected for reliability of measurement, were consistent with moderate
      heritabilities. In accord with studies examining Asian samples, we found that
      individuals who experienced adverse reactions after drinking small amounts of
      alcohol drank less often and slightly less per drinking occasion than those who
      did not experience adverse reactions. However, those who experienced adverse
      reactions were more likely to have symptoms of alcoholism and to report a
      parental history of alcohol problems. We conclude that self-reported alcohol
      related flushing is not a protective factor for alcoholism in Caucasians and may
      be a risk factor.

PMID- 7573780
TI  - Development and initial validation of a measure of drinking urges in abstinent
      alcoholics.
AB  - Although drinking urges and cravings are commonly reported by alcoholics,
      prospective studies have found inconsistent associations between such urges and
      drinking relapses. Previous studies have measured drinking urges by use of single
      item ratings of alcohol craving or other measures of unknown reliability and
      validity. To permit improved evaluation of hypotheses regarding alcohol craving,
      a 49-item questionnaire that reflects several urge-related domains was developed
      and pretested. Items assessed subjects' desire for a drink, expectations of
      positive effects following drinking, relief of withdrawal and negative affect
      following drinking, and intention to drink. Exploratory and confirmatory factor
      analyses of the responses of 351 abstinent, treatment-seeking alcoholics
      indicated that alcohol urges are best described by a single factor. Based on
      these analyses, an internally consistent, reliable, and psychometrically valid 8
      item scale, the Alcohol Urge Questionnaire (AUQ), was developed. Data indicated
      that AUQ scores were strongly related to alcohol dependence severity and to
      cognitive preoccupation with alcohol, and that they declined with prolonged
      abstinence. The AUQ may be useful in alcoholism treatment research and in
      laboratory studies of reactivity to alcohol or other manipulations.

PMID- 7573779
TI  - Effects of disease-related cues in alcoholic inpatients: results of a controlled
      "Alcohol Stroop" study.
AB  - We tested the hypothesis that alcoholics develop a disease-related attentional
      bias. Therefore, alcohol-related, but task-irrelevant, words should cause a
      specific perceptual-processing bias. We investigated this by using a special
      color-naming task. We subjected 40 male alcohol-dependent inpatients and 40
      healthy male controls (matched according to age and verbal IQ) to a modified card
      version of the Stroop color-naming task that consisted of a neutral and an
      alcohol word condition ("Alcohol Stroop"). Alcoholic inpatients performed
      significantly poorer than the control group under the critical experimental
      condition (color-naming of disease-related words), as compared with the
      noncritical condition (color-naming of neutral words; p = 0.03). Concerning the
      possible neuropsychological impairment of the patients, no effects could be found
      on the reaction time of the "Standard Stroop" using only neutral words (i.e.,
      color-naming of incongruent color words administered without time limitation).
      The information processing bias on the "Alcohol Stroop" thus qualifies as a
      cognitive process, which is independent from putative neuropsychological deficits
      of alcoholic patients and might represent an essential feature of alcoholic
      psychopathology. The "Alcohol Stroop" contributes to the experimental
      psychopathology of alcoholism.

PMID- 7573781
TI  - Low dose of ethanol suppresses mismatch negativity of auditory event-related
      potentials.
AB  - The acute effect of a low dose of ethanol (0.5 g/kg) on attention and auditory
      event-related potentials (ERPs) was investigated in 10 social drinkers using a
      single-blind, placebo-controlled cross-over design. A dichotic listening task, in
      which the subjects were instructed to attend selectively to stimuli to one ear
      while ignoring stimuli to the other, was used. The amplitudes of N1, P2, and the
      mismatch negativity (MMN) were significantly diminished by alcohol. The latencies
      of the MMN and N2b were also significantly increased after alcohol ingestion. The
      novel finding of the significant (> 60% reduction in amplitude) suppression of
      the MMN can be interpreted as indicating disturbed preconscious detection of
      acoustic changes outside the scope of attention. Because this is a prerequisite
      to an attentional shift, the MMN suppression may be related to increased risk for
      accidents after alcohol ingestion. The same dose of alcohol that suppressed the
      MMN left intact selective attention and conscious "target" detection, as
      reflected by the processing negativity and P3 deflections, thus suggesting that
      the automatic functions of human information processing are more sensitive to
      alcohol than the controlled, attentional functions.

PMID- 7573782
TI  - Utility of carbohydrate-deficient transferrin as a marker of relapse in alcoholic
      patients.
AB  - Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of
      alcoholism. However, its role in monitoring alcoholic patients for relapse has
      not been extensively studied. We therefore performed sequential serum CDT
      measurements using a microcolumn/radioimmunoassay method (Kabi Pharmacia,
      Piscataway, NJ) in 86 male alcoholics participating in a hepatitis vaccination
      program who were monitored for relapse using self-report and collateral history
      (when available). The maximum serum CDT was significantly higher in patients who
      relapsed (n = 38) (33.1 +/- 3.1 mg/liter), as compared with abstinent subjects
      with collateral verification (n = 39) (18.8 +/- 1.3, p < 0.001) and abstinent
      patients without collateral verification (n = 9) (17.4 +/- 1.3, p < 0.01). Using
      the manufacturer's currently recommended threshold of 20 mg/liter for males,
      serum CDT was elevated in 29 of 38 patients who relapsed (sensitivity 76.3%). In
      16 (42.1%) of the relapsed patients, a serum CDT above this threshold preceded
      the patient's self-report by at least 28 days. However, serum CDT exceeded 20
      mg/liter in 10 of 48 patients who remained sober (specificity 79.2%); three of
      these patients had clinical and/or pathological evidence of cirrhosis. Using a
      threshold of 25 mg/liter, 21 of 38 patients who relapsed had an elevated serum
      CDT (sensitivity 55.3%); 12 (31.6%) of these patients had elevated serum CDT
      before self-report. Only 4 of 48 subjects who remained sober had serum CDT levels
      that exceeded 25 mg/liter (specificity 91.7%); three of these patients had
      clinical and/or pathological evidence of cirrhosis. In conclusion, serial serum
      CDT testing detects relapses before self-report in male subjects. Values between
      20-25 mg/liter suggest relapse, but call for collateral verification, whereas CDT
      values above 25 mg/liter are usually diagnostic of relapse in the absence of
      cirrhosis.

PMID- 7573784
TI  - Relationships between socioeconomic status and drinking problems among black and
      white men.
AB  - We sought to examine the relationships between socioeconomic status and drinking
      problems within the Black and White male populations. A two-way interactions of
      social class with race/ethnicity, and with drinking consequences and alcohol
      dependence symptoms was hypothesized among drinkers. Drinking problems were
      regressed on social class, race/ethnicity, age, alcohol consumption, and drinking
      settings. Social class was based on a composite of respondent's income,
      education, and main wage earner's occupation. Two types of drinking problems were
      analyzed: drinking consequences and alcohol dependence symptoms. Our hypothesis
      was partially confirmed. Interactions of social class with race/ethnicity and
      with drinking problems were observed. Less affluent Black men reported greater
      numbers of drinking consequences and total drinking problems than less affluent
      White men; the reverse was true for affluent Black and White men. Results suggest
      that the relationships between socioeconomic status and drinking problems may
      vary by race/ethnicity.

PMID- 7573785
TI  - Ethnic differences in performance of screening instruments for identifying
      harmful drinking and alcohol dependence in the emergency room.
AB  - This study examines sensitivity and specificity figures associated with screens
      used to predict harmful drinking and alcohol dependence among current drinkers.
      The study population comes from a probability sample of emergency room patients
      in Jackson, MS. Data are presented by gender and injury status (injured versus
      noninjured) for Blacks and for Whites. The Composite International Diagnostic
      Interview was used to assess ICD-10 criteria for harmful drinking and alcohol
      dependence, which were taken as standards. Predictors include screening
      instruments (CAGE, AUDIT, brief MAST, TWEAK, and History of Trauma Scale),
      breathalyzer reading, self-reported consumption before the injury or noninjury
      event, quantity and frequency of drinking, and an abbreviated alcohol dependence
      experiences measure used in general population surveys. Single items from these
      screening instruments were also tested as predictors. Overall, the TWEAK and the
      AUDIT performed best in terms of sensitivity and specificity, but variation
      across subgroups suggests that the search for a good screening instrument for
      general use must be continued.

PMID- 7573783
TI  - Acute effects of alcohol on P300 in Asians with different ALDH2 genotypes.
AB  - Asian men were genotyped for alleles of aldehyde dehydrogenase (ALDH2) and tested
      on two separate occasions following oral administration of placebo and 0.75 ml/kg
      alcohol. Sixty minutes after beverage ingestion, event-related potentials were
      elicited using an auditory oddball paradigm. Repeated measures ANOVA revealed
      that alcohol produced significant increases in P300 latency and significant
      decreases in P300 amplitude compared with placebo. Subjects with ALDH2*1/2*2
      genotype (n = 14) demonstrated some significantly greater P300 effects after
      alcohol than subjects with ALDH2*1/2*1 genotype (n = 15), despite equivalent
      blood alcohol concentrations. These data suggest that neurocognitive functioning
      may be more impaired following alcohol in subjects with an ALDH2*2 allele. These
      findings further suggest that a genetically controlled factor (deficiency in ALDH
      enzyme activity) might contribute to a decreased likelihood of alcohol intake and
      protection from alcoholism, because of an enhanced sensitivity to alcohol.

PMID- 7573787
TI  - Aggressivity in adolescent alcohol abusers: relationship with conduct disorder.
AB  - Several longitudinal and retrospective studies have documented an association
      between premorbid aggression and an increased risk for an alcohol-use disorder in
      adulthood. However, few data are available examining the relationship between
      trait aggressivity, alcohol use behavior, and the presence of an early-onset
      alcohol use disorder diagnosis among the adolescent population. To address this
      deficiency, this study had three goals. First, the relationship between
      aggressivity and adolescent alcohol consuming behavior was examined. Second, the
      presence and magnitude of trait aggressivity were determined among adolescents
      who met psychiatric diagnostic criteria for alcohol abuse/dependence (ALC), while
      controlling for the presence of a conduct disorder (CD). Third, because CD is
      overrepresented among adolescent alcohol abuse cases and is a priori defined by
      the presence of certain aggressive behaviors, the simultaneous contributions of
      CD and ALC on trait aggressivity were also investigated through structural
      equation modeling. The results confirm the salience of heightened aggressivity as
      an essential feature of this early-onset alcohol-abusing population and indicate
      the importance of addressing this behavioral domain in prevention and treatment
      efforts.

PMID- 7573786
TI  - Relationship of protein calorie malnutrition to alcoholic liver disease: a
      reexamination of data from two Veterans Administration Cooperative Studies.
AB  - The relationship of protein calorie malnutrition (PCM) to alcoholic liver disease
      was studied in 666 patients enrolled in two Veterans Administration Cooperative
      Studies. Some findings of malnutrition could be detected early in 62% of the
      comparison patients (43 subjects who were alcoholic, but had not yet developed
      clinical or laboratory evidence of liver injury). In those who had progressed to
      the stage of liver injury sufficient to manifest clinical jaundice (536
      patients), some findings of malnutrition were present in every patient (100%).
      The degree of malnutrition correlated closely with the development of all the
      serious complications of the liver disease (ascites, encephalopathy, and
      hepatorenal syndrome), as well as the overall mortality. The degree of
      malnutrition was also important in predicting response to some forms of
      treatment. When prednisolone, a catabolic adrenal steroid, was used, efficacy was
      independent of the level of malnutrition. However, a relationship was observed
      with the severity of the liver injury [quantified by the level of jaundice and
      coagulopathy, i.e., Maddrey's discriminant function (DF(Maddrey)]. For
      prednisolone, the response was seen only when the DF was 81-100 reducing
      mortality 45% When oxandrolone, an androgenic anabolic steroid treatment was
      given, efficacy was observed only in those with moderate malnutrition (PCM score
      60-79% of normal) and maximized with adequate caloric intake reducing mortality
      86%. To simplify the method of calculating the PCM score for predicting response
      to anabolic therapy, a multiple logistic regression model was developed from the
      parameters used to assess nutritional status: DF(PCM) = 0.098 (peripheral blood
      lymphocytes) + 0.078 (creatinine height index).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573788
TI  - Occupational stress and the risk of alcohol abuse and dependence.
AB  - Using prospective data, we examined the relationship between occupational stress
      and risk for alcohol disorders. Consistent with the Demand/Control model for
      psychosocial work environments, we hypothesized that individuals working in high
      strain occupations (jobs with high demands and low control) would be at increased
      risk for alcohol abuse-dependence relative to those in low-strain occupations
      (jobs with low demands and high control). We classified high occupational strain
      into two categories: (1) jobs with high psychological demands and low control,
      and (2) those with high physical demands and low control. A total of 18,571 study
      subjects were selected in 1980-1984 by taking probability samples of adult
      household residents at five sites of the Epidemiologic Catchment Area Program. At
      baseline, participants completed standardized interviews that measured
      sociodemographic variables and assessed whether they had met diagnostic criteria
      for currently or formerly active alcohol abuse-dependence syndromes. The
      interviews were readministered 1 year later to identify cases among the
      participants. Subjects were sorted into risk sets by age and residence census
      tract, and persons with a previous history of alcohol abuse or dependence, as
      well as those who were over 64 years or had no history of full-time employment,
      were excluded. Among the 507 participants included in the risk sets, there were
      126 incident cases of alcohol abuse-dependence and 381 age and residence-matched
      noncases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573789
TI  - Late-onset seizures in alcohol withdrawal.
AB  - PURPOSE: To describe the clinical characteristics of alcohol withdrawal seizures
      in patients treated with a standardized protocol of short-acting benzodiazepines.
      METHODS: Grand mal seizures were prospectively identified in a cohort of 1044
      patients consecutively admitted to an inpatient alcohol detoxification unit at a
      Veterans Affairs Medical Center. All patients received a 72-hr structured taper
      of oxazepam with additional oxazepam given without limit in amount and duration
      in response to alcohol withdrawal symptoms. RESULTS: Eleven seizures occurred for
      an overall rate of 1.1%. All were single grand mal seizures. Seizures occurred
      from 52 to 306 hr after admission, with a mean of 122 hr (5 days). A consistent
      relationship between the seizures and the cessation of oxazepam was noted, with
      peak incidence occurring 12-48 hr after the last oxazepam dose. In no case did
      recurrent withdrawal symptoms or delirium tremens develop after the seizure.
      Patients with seizures were slightly older, more likely to have had withdrawal
      seizures before (50% vs. 13%, p = 0.03), and had a more severe withdrawal course
      than controls. CONCLUSIONS: Seizures continued to occur at a low but measurable
      rate in alcohol withdrawal treated with a short-acting benzodiazepine. Clinical
      characteristics of the seizures are different from that classically described in
      untreated patients, with the seizures being closely related to the cessation of
      oxazepam rather than the cessation of alcohol.

PMID- 7573790
TI  - Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a
      series of case reports.
AB  - Although autistic-like behaviors were described even in the earliest reports of
      fetal alcohol syndrome, it was only recently that fetal alcohol syndrome and
      autism were reported as a dual diagnosis in six school-aged children. The purpose
      of the present series of case reports is to describe marked autistic
      characteristics in three much younger children (25-36 months) with histories of
      prenatal exposure to alcohol and other drugs. The behavioral characteristics of
      these children are described and compared with current diagnostic criteria for
      autistic disorder. In addition, longitudinal scores on the Bayley Scales of
      Infant Development are provided to underscore the marked developmental delays
      shown by each of the children. Limitations of these case reports are discussed
      with suggestions for future prospective research.

PMID- 7573792
TI  - Voice of the victims.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from the victims can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcoholism.

PMID- 7573791
TI  - Drinking patterns and health status in smoking and nonsmoking alcoholics.
AB  - Alcoholics who smoked also reported that they drank more frequently and consumed
      more alcohol on drinking occasions than alcoholics who did not smoke, a practice
      that resulted in a substantially greater lifetime alcohol consumption in the
      smokers. Smoking alcoholics also consumed more cigarettes and reported more
      smoking-related physical symptoms than social drinkers who smoked. The heart
      rates (HRs) of smoking and nonsmoking alcoholics were similar and both exceeded
      the HRs for the smoking social drinkers by approximately 13 beats/min (bpm) in
      males and by approximately 7 bpm in females. Surprisingly, correlations between
      HR and lifetime alcohol consumption were higher and slopes were steeper in
      controls than in alcoholics. HRs in a subset of the male alcoholics fell only
      approximately 3 bpm after 24 weeks of abstinence, but changed no further over an
      additional 24-week period. Taken together, the findings suggest that HRs may have
      been higher in this group of alcoholics before the onset of alcohol abuse and
      that alcohol intake contributed only slightly to the high HR.

PMID- 7573793
TI  - Effect of ethanol on function of the rat heart and skeletal muscles.
AB  - The present study was undertaken to evaluate the acute effects of ethanol on
      responses of the rat heart and skeletal muscles both in vivo and in vitro. In the
      anesthetized rat, intravenous infusion of ethanol at 0.1-0.5 g/kg body weight (33
      167 mM) decreased the breathing rate by 8-83%, heart rate by 4-52%, and QRS
      amplitude by 5-27%, and increased the P-R interval by 1-49%. In the anterior
      tibialis muscle subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec,
      ethanol at 0.1 g/kg increased the amplitude of the muscle action potential (AP)
      by 7%, whereas at 0.5 g/kg it decreased the muscle AP by 32%. The nerve-evoked
      tetanic tension was reduced by 7-34% at 0.1-0.5 g/kg ethanol. In the isolated rat
      heart, perfusion of ethanol at 0.1-3.0% (22-651 mM) decreased the heart rate by 8
      48% and QRS amplitude by 10-39%, and increased the P-R interval by 5-61%. Left
      ventricular pressure was increased by 10% at 0.1% ethanol, and decreased by 80%
      at 3.0% ethanol. In the isolated rat phrenic nerve-diaphragm muscle preparation
      subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol
      decreased the amplitude of the nerve AP by 5-89%, nerve-evoked muscle AP by 2
      96%, and peak tetanic tension by 1-87%. On repetitive direct muscle stimulation
      at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the muscle
      evoked muscle AP by 8-65%, and muscle-evoked tetanic tension by 2-65%. These
      studies indicate that ethanol causes smaller reduction in responses of the heart
      and skeletal muscles at clinical concentrations, but marked reduction in these
      responses at higher concentrations due to direct action on excitability of these
      tissues. At higher concentrations, ethanol causes greater reduction in
      excitability of the skeletal muscle than of the heart.

PMID- 7573794
TI  - Effects of chronic alcohol abuse and HIV infection on brain phosphorus
      metabolites.
AB  - We examined the effects of human immunodeficiency virus (HIV) infection and
      chronic alcohol consumption on cerebral phosphorus metabolites to determine if
      chronic alcohol abuse is a risk factor for the progression of neurological
      effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV-
      light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with
      both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31
      phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to
      examine two brain volumes in superior white matter and subcortical gray matter.
      Chronic alcohol consumption was associated with reduced white matter
      concentrations of phosphodiester (PDE) and phosphocreatine (PCr). Also in the
      white matter, acquired immune deficiency syndrome (AIDS) and AIDS-related complex
      (ARC) were associated with reduced concentrations of PDE and PCr, compared with
      both HIV- and clinically asymptomatic HIV+ subjects. Because no alcohol-by-HIV
      interactions were detected, the effects of HIV infection and alcohol abuse were
      cumulative. This is reflected in a successive decrease of white matter PDE and
      PCr concentrations in the order HIV- light/nondrinkers/HIV- alcoholics/HIV+
      light/nondrinkers/HIV+ alcoholics. Subcortical gray matter PDE concentrations
      were lower in ARC/AIDS alcoholics than in HIV- light/nondrinking individuals.
      These findings suggest altered brain phospholipid metabolites and energy
      metabolites with alcohol abuse and HIV infection. They demonstrate that the
      adverse metabolic effects of HIV on the brain are augmented by chronic alcohol
      abuse.

PMID- 7573796
TI  - Insulin signaling in chick embryos exposed to alcohol.
AB  - Although insulin is known to be an important generator of regulatory signals
      during fetal growth and development, neither the immediate nor long-term effects
      of alcohol (ethanol) on insulin action are well understood. In the rat, fetal
      exposure to alcohol has been shown to be correlated with a subsequent abnormal
      response to a glucose load in the neonate and adult. Further, fetal hypoplasia
      secondary to maternal alcohol consumption is correlated with decreased placental
      glucose transport and with a lowering of the glucose levels in fetal tissues.
      However, the fetal effects of alcohol cannot be completely overcome by
      glucose/caloric supplementation, suggesting that factors other than glucose
      transport are involved. Using an embryonic chick model that negates the factors
      of maternal/placental metabolism and transport, the current study found that
      fetal alcohol exposure markedly increased insulin binding in developing tissue,
      but had little effect on the binding of the insulin-like growth factors.
      Competitive binding experiments revealed a marked increase in insulin receptor
      numbers, but no change in binding affinity as a result of the alcohol exposure.
      Basal uptake of 2-deoxyglucose by fetal tissue was lowered by alcohol exposure,
      but incubation with exogenous porcine insulin (1 x 10(-7) M) resulted in a
      significant increase in glucose uptake by the alcohol-exposed embryos. The
      increases in insulin binding and in insulin-dependent glucose uptake
      notwithstanding, exogenous insulin could not induce normal levels of ornithine
      decarboxylase activity in embryonic cells previously exposed to alcohol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573795
TI  - Low-level hyperbaric exposure antagonizes locomotor effects of ethanol and n
      propanol but not morphine in C57BL mice.
AB  - Low-level hyperbaric exposure antagonizes a broad range of behavioral effects of
      ethanol in a direct, reversible, and competitive manner. This study investigates
      the selectivity of the antagonism across other drugs. C57BL/6 mice were injected
      with saline, ethanol, n-propanol, or morphine sulfate, and then were exposed to 1
      atmosphere absolute (ATA) air, 1 ATA helium-oxygen gas mixture (heliox), or 12
      ATA heliox. Locomotor activity was measured from 10 to 40 min following
      injection. N-propanol produced a dose-dependent depression of locomotor activity
      from 1.0 g/kg. Morphine produced a dose-dependent stimulation of locomotor
      activity at doses of 3.75-12.0 mg/kg. Exposure to 12 ATA heliox significantly
      antagonized the locomotor depressant effects of 1.0 g/kg n-propanol and 2.5 g/kg
      ethanol, without significantly affecting blood concentrations of these drugs
      measured at 40 min postinjection. Exposure to 12 ATA heliox did not significantly
      antagonize the locomotor-stimulating effects of the two morphine doses tested
      (3.75 and 7.5 mg/kg). These findings suggest that exposure to 12 ATA heliox
      antagonizes the behavioral effects of intoxicant-anesthetic drugs like ethanol
      and n-propanol, which are believed to act via perturbation or allosteric
      modulation of functional proteins, but does not antagonize the effects of drugs
      like morphine, which act via more direct mechanisms. This demonstration of
      selective antagonism adds important support for the hypothesis that low-level
      hyperbaric exposure is a direct mechanistic ethanol antagonist, with
      characteristics similar to a competitive pharmacological antagonist.

PMID- 7573797
TI  - Gonadal hormones and aggression-maintaining effect of alcohol in male transgenic
      transforming growth factor-alpha mice.
AB  - We have characterized a new transgenic mouse model that offers the unique
      opportunity to study the biological mechanisms linking aggression to alcohol. In
      contrast to all other aggressive animal models, the male transgenic mice that
      overexpress transforming growth factor-alpha (TGF-alpha) maintain their highly
      elevated aggressive behavior following an alcohol administration. The transgenic
      mice also exhibit elevated plasma levels of 17 beta-estradiol (E2). Animal data
      support the role of E2 in aggression and alcohol intake in males. Further, type 2
      alcoholism is male-limited, suggesting that gonadal hormones are important. We
      examined whether gonadal hormones play a role in the resistance to respond to
      alcohol in the resident-intruder test of aggression among the male transgenic TGF
      alpha mice. As previously reported, alcohol had a biphasic effect on sham
      operated, nontransgenic controls: 0.6 g/kg increased and 2.0 g/kg inhibited their
      aggressiveness. Alcohol did not significantly reduce the high levels of
      aggression in the sham-operated TGF-alpha mice. Castration abolished the
      difference in aggressive behavior between the transgenic and nontransgenic male
      mice by reducing aggression. Alcohol did not increase aggressive behavior in
      these mice. Treatment with pellets releasing 0.25 mg E2 over a 60-day period
      increased aggression in the castrated male TGF-alpha mice and nontransgenic
      controls to the levels seen in intact male transgenic mice. Alcohol did not
      significantly alter aggressive behavior in the E2-treated castrated
      mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573801
TI  - Equilibrative adenosine transport in rat hepatocytes after chronic ethanol
      feeding.
AB  - Acute treatment of cells with ethanol in vitro inhibits adenosine uptake via
      equilibrative nucleoside transporters. After longer periods of exposure to
      ethanol in culture, rechallenge with ethanol no longer inhibits adenosine uptake.
      Herein, we have investigated the long-term effects of ethanol consumption in vivo
      on equilibrative nucleoside transport. Rats were fed a liquid diet containing 35%
      of calories as ethanol (ethanol-fed). Control rats were pair-fed a liquid diet
      that isocalorically substituted maltose dextrins for ethanol. After 4 weeks of
      ethanol consumption, nucleoside transport was measured in isolated hepatocytes.
      Uptake of [3H]adenosine was lower in ethanol-fed rats compared with control.
      Influx of the nonmetabolizable nucleoside analog, [3H]formycin B, was also
      decreased after ethanol feeding. However, neither the number of
      nitrobenzylthioinosine (NBMPR) binding sites or inhibition of adenosine uptake by
      NBMPR were affected by ethanol feeding. In controls, acute treatment of isolated
      hepatocytes with 100 mM ethanol inhibited [3H]adenosine uptake by 30-40%.
      However, in ethanol-fed rats, acute challenge with ethanol did not inhibit
      [3H]adenosine uptake. These data demonstrate that long-term ethanol feeding
      decreases equilibrative nucleoside transport in hepatocytes independent of a
      change in the number of nucleoside transporters and renders adenosine uptake
      insensitive to inhibition by ethanol.

PMID- 7573800
TI  - Effect of prenatal ethanol and stress on levels of beta-endorphin in different
      brain regions of the rat.
AB  - The combination of prenatal ethanol exposure and footshock stress was
      investigated for its effects on brain beta-endorphin levels. Subjects were
      offspring of rats that received 1 of 3 prenatal dietary treatments: an ethanol
      containing liquid diet, a identical liquid diet with ethanol substituted
      isocalorically with maltose-dextrin (pair-fed group), and standard laboratory rat
      chow (chow-fed group). Two different stress paradigms were used: a short (30-sec)
      footshock stress paradigm and a prolonged (180-sec) footshock stress paradigm.
      Levels of beta-endorphin were measured with radioimmunoassay in eight brain
      regions of unstressed (baseline) rats, and of stressed rats at 3 and 30 min
      following termination of the stress. Seven brain regions containing high
      densities of beta-endorphin axons and terminals were chosen, as well as the
      arcuate region of the hypothalamus, the only brain region where both beta
      endorphin perikarya and terminals are located. Following the short footshock
      stress paradigm, there were no changes in beta-endorphin levels, except for a
      trend toward increased levels in the pair-fed group. After the prolonged stress
      paradigm, levels of beta-endorphin in both the pair-fed and chow-fed groups
      tended to be decreased in several brain regions, including the arcuate region, at
      3 min after termination of the stress. In contrast, for the prenatally ethanol
      exposed group, beta-endorphin levels were increased significantly in the arcuate
      region, and moderately increased in the septal/preoptic region and medulla/pons
      at 3 min after the prolonged stress paradigm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573799
TI  - Attenuation of glutamate-induced neurotoxicity in chronically ethanol-exposed
      cerebellar granule cells by NMDA receptor antagonists and ganglioside GM1.
AB  - Ethanol, acutely, is a potent inhibitor of the function of the N-methyl-D
      aspartate (NMDA) subtype of glutamate receptor. After chronic exposure of animals
      to ethanol, however, the NMDA receptor in brain is upregulated. This upregulation
      is associated with the occurrence of ethanol withdrawal seizures. When cultured
      cerebellar granule neurons are exposed chronically to ethanol, the resulting
      upregulation of NMDA receptor function renders the cells more susceptible to
      glutamate-induced neurotoxicity. The present studies show that chronic ethanol
      exposure produces an increase in NMDA receptor number in the cells, measured by
      ligand binding to intact cells. Glutamate-induced excitotoxicity, both in control
      and ethanol-exposed cells, is blocked by the same NMDA receptor antagonists
      previously shown to block ethanol withdrawal seizures in animals. In addition,
      glutamate neurotoxicity is blocked by acute (2-hr) pretreatment of cells with
      ganglioside GM1 or by chronic (3 days) treatment with the ganglioside. Acute
      ganglioside treatment does not interfere with the initial rise in intracellular
      calcium caused by glutamate, whereas this response is downregulated after chronic
      ganglioside treatment. These results suggest that therapeutic agents can be
      developed to block both ethanol withdrawal signs and the neuronal damage that
      accompanies ethanol withdrawal. Furthermore, chronic ganglioside treatment during
      ethanol exposure has the potential to prevent changes in the NMDA receptor that
      lead to withdrawal seizures and enhanced susceptibility to excitotoxicity.

PMID- 7573798
TI  - In utero ethanol exposure elicits oxidative stress in the rat fetus.
AB  - Prior studies in our laboratory have shown that exposure of cultured fetal rat
      hepatocytes to ethanol (E) blocks epidermal growth factor-dependent replication
      and that this is paralleled by cell membrane damage, mitochondrial dysfunction,
      membrane lipid peroxidation (LP), and enhanced generation of reactive oxygen
      species. These measures of E-mediated oxidative stress (OS) were mitigated by
      treatment with antioxidants, and cell replication could be normalized by
      maintaining cell glutathione (GSH) pools. We have now extended these studies to
      an in vivo model. Rats were administered E (4 g/kg, po) at 12-hr intervals on
      days 17 and 18 of gestation and killed on day 19, 1 hr following a final dose of
      E (a total of 5 doses). Fetal and maternal brain and liver were assayed for signs
      of OS. The 2-day in utero E exposure increased membrane LP in fetal brain as
      evidenced by increased malondialdehyde (MDA) levels from 1.76 +/- 0.12 SE
      (nMol/mg protein) to 2.00 +/- 0.08 (p < 0.05) and conjugated dienes from 0.230 +/
      0.006 SE (OD223/mg lipid) to 0.282 +/- 0.006 (p < 0.05). In fetal liver, MDA
      levels increased from 2.39 +/- 0.08 SE (nMol/mg protein) to 2.87 +/- 0.08 (p <
      0.05), whereas dienes differed significantly only between ad libitum controls and
      the E and pair-fed control groups (p < 0.05). E decreased GSH levels in fetal
      brain by 19%, from 19.88 +/- 0.72 to 16.13 +/- 1.06 (nMol/mg protein) (p < 0.05).
      A 10% decrease in GSH was seen in fetal liver (p < 0.05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7573803
TI  - Changes in the fatty acid profile of plasma and adipose tissue in rats after long
      term ethanol feeding.
AB  - The effect of chronic ethanol feeding on the fatty acid composition of plasma and
      abdominal adipose tissue in rats was studied. Animals were maintained on a 30%
      ethanol solution in drinking water for 3 and 5 months. Control rats were given
      water. Caloric intake was similar in control and ethanol-fed rats at the end of
      the experimental period. However, a decrease in body weight was observed in rats
      that had consumed ethanol. Palmitoleic (16:1n7) and oleic (18:1n9) acids
      increased markedly, and linoleic acid (18:2n6) decreased in the plasma and in the
      adipose tissue of ethanol-fed rats with respect to control rats. After 3 months
      of ethanol ingestion, long-chain polyunsaturated fatty acids were reduced both in
      plasma and adipose tissue. When ethanol was administered for 5 months, only
      plasma long-chain polyunsaturated fatty acids of the n-3 series were decreased.
      This suggest that changes induced by ethanol ingestion in essential fatty acid
      metabolism is less pronounced when ethanol feeding is maintained for a long
      period of time.

PMID- 7573804
TI  - Induction of HSP72 in rat liver by chronic ethanol consumption combined with
      exercise: association with the prevention of ethanol-induced fatty liver by
      exercise.
AB  - Ethanol-induced fatty liver in rats was attenuated by repeated running exercise,
      and the protective effect of exercise was associated with the synergistic
      expression of heat shock proteins (HSP72). Rats were placed in four groups of
      six. The two ethanol-fed groups of rats received a liquid diet (Lieber-DeCarli
      formulation) in which 36% of the calories were derived from ethanol. One group
      remained sedentary (S/E), whereas the other was trained to run on a rodent
      treadmill at a speed of 27 m/min, 1 hr/day, 5 days/week, for 7 weeks (R/E). Two
      other groups--one exercised as previously mentioned (R/C) and one sedentary (S/C)
      -received control-liquid diets in which the ethanol was isocalorically
      substituted with a dextran/maltose mixture. The degree of fatty infiltration in
      liver sections stained with hematoxylin and eosin was graded on a 0-4 scale and
      the data analyzed by ANOVA on ranks. Ethanol significantly induced fatty
      infiltration in the S/E group, whereas fatty infiltration in the livers of the
      R/E group was not different from the S/C group. Electrophoresis and Western
      blotting of liver homogenates demonstrated that HSP72 was not expressed in either
      the S/C or S/E groups and was only slightly expressed in the R/C group. The
      combination of exercise and ethanol, however, resulted in an elevated expression
      of HSP72 in the R/E group. The content of HSP73 was unaffected by any treatment.

PMID- 7573802
TI  - Effect of ethanol on prostacyclin, thromboxane, and prostaglandin E production in
      human umbilical veins.
AB  - The purpose of this study was to determine the effects of ethanol on prostacyclin
      (PGI2), prostaglandin E (PGE), and thromboxane (TXA2) production in perfused
      human umbilical veins. PGI2, PGE, and TXA2 levels were measured from human
      umbilical veins perfused with either 25, 50, or 100 mM ethanol by
      radioimmunoassay of their stable metabolites. Alcohol content was measured by an
      enzymatic spectrophotometric assay. Data were analyzed by ANOVA and Fisher's
      Protected Least Significant Difference Test. Ethanol decreased PGI2 production in
      a concentration-dependent manner (p < 0.05). In a concentration of 25 mM, ethanol
      did not affect PGI2 production, whereas 50 mM decreased levels after 60 min of
      perfusion (p < 0.01). With 100 mM ethanol, PGI2 production was decreased after
      15, 30, and 60 min of perfusion (ps < 0.05), and the TXA2/PGI2 ratio was
      significantly elevated at all time points (p < 0.01). Ethanol (100 mM) did not
      affect TXA2 or PGE production. Reduction of PGI2 levels and the increase in the
      TXA2/PGI2 ratio seen after ethanol perfusion in umbilical veins may cause
      vascular disruption in the umbilical-placental circulation. This may, in part, be
      a contributing mechanism to the teratogenic effects of ethanol.

PMID- 7573805
TI  - Role of plasma vasopressin in changes of water balance accompanying acute alcohol
      intoxication.
AB  - Acute alcohol intoxication causes diuresis presumably resulting from inhibition
      of vasopressin (also called antidiuretic hormone) release from the posterior
      pituitary gland. In contrast, in alcoholics during withdrawal from alcohol,
      vasopressin release is stimulated, resulting in water retention (antidiuresis)
      and dilutional hyponatremia. The purpose of this study was to evaluate the role
      of this biphasic response of vasopressin secretion to alcohol in normal persons.
      We studied eight healthy men who took part in two study sessions: one involving
      the ingestion of ethanol (1.2 g/kg of body weight) and the other the ingestion of
      the same volume of fruit juice during 3 hr from 6 to 9 PM. Starting at 6 AM the
      following morning, subjects were loaded with water (20 ml/kg of body weight
      within 15 min). During the first 3 hr of the study, ethanol intake increased
      diuresis, whereas from midnight to 6 AM, a phase of antidiuresis was obtained.
      Antidiuresis continued during water loading when the retention of water was 44 +/
      6% during the alcohol experiment and 12 +/- 4% during the control session (p <
      0.05). During the alcohol-induced diuresis, the plasma arginine vasopressin
      levels did not differ from the control experiment, but were higher during the
      phase of antidiuresis from 10 PM to 6 AM (p < 0.05- < 0.01). Also, after water
      loading at 8 and 9 AM, they were higher in the alcohol study than in the control
      experiment (p < 0.05). After alcohol ingestion, serum osmolality was higher than
      the corresponding control values from 8 PM to 2 AM (p < 0.01- < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573806
TI  - Low doses of ethanol impair spatial working memory and reduce hippocampal theta
      activity.
AB  - Low doses of ethanol can alter neural activity in the septohippocampal pathway, a
      pathway critical for spatial working memory. The present study was designed to
      determine whether acute ethanol induces impairments in working memory and
      disrupts septohippocampal function as measured by the hippocampal theta rhythm.
      Rats were preoperatively trained on delayed alternation. A within-subject design
      was used to evaluate the effects of ethanol (0.25, 0.5, 0.75 and 1.0 g/kg,
      intraperitoneally) on performance 10 min and 90 min after injection as compared
      with preinjection baseline. Ethanol produced dose-, delay-, and time-dependent
      impairments in working memory as indicated by a change in choice accuracy in the
      delayed alternation task. Ethanol did not affect performance time, the ability to
      complete the task, or response bias. Thus, the impairment does not appear to
      result from a decrement in general performance, but rather from an impairment in
      spatial working memory. Hippocampal theta activity was suppressed by ethanol at
      the same doses, 0.75 g/kg and 1.0 g/kg, that impaired working memory. The
      interaction of ethanol with functions of the septohippocampal pathway are
      discussed.

PMID- 7573807
TI  - Low-dose effect of ethanol on locomotor activity induced by activation of the
      mesolimbic system.
AB  - Four experiments were designed to study the ability of 0.5 g/kg ethanol (EtOH)
      intraperitoneally to modify locomotor activity induced by drugs that interact
      with different sites in the mesolimbic system (MLS) of male Sprague-Dawley rats.
      Locomotor activity was measured in a doughnut-shaped circular arena after various
      treatments. EtOH alone did not alter locomotor activity in any of the
      experiments. Amphetamine (AMP, intraperitoneally or intraaccumbens) increased
      locomotor activity in a dose-dependent manner, and the presence of EtOH
      attenuated AMP-induced locomotor activity. Bilateral infusion of GABAA antagonist
      picrotoxin (PIC) into the ventral tegmental area also increased locomotor
      activity in a dose-dependent manner, and the presence of EtOH attenuated PIC
      induced locomotor activity. On the other hand, the interaction between bilateral
      infusion of mu-receptor agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and EtOH on
      locomotor activity is complex. The highest dose of DAGO that significantly
      increased locomotor activity was not affected by the presence of EtOH. But, with
      lower doses of DAGO that either had no effect or a small increase in locomotor
      activity, the combination of EtOH and DAGO increased and attenuated locomotor
      activity, respectively. Results from this study support our hypothesis that a low
      dose of EtOH that does not modify behavior can interact with neurotransmitter
      systems in the brain and modify drug-induced locomotor activity. Modification of
      this drug-induced locomotor activity by a low dose of EtOH is dependent on the
      rate of ongoing locomotor behavior induced by drug and the neurotransmitter
      substrate that the drug modified to induce locomotor behavior.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7573810
TI  - Evaluating new tests for the diagnosis of food allergy.

PMID- 7573808
TI  - Possible central adenosinergic modulation of ethanol-induced alterations in
      [14C]glucose utilization in mice.
AB  - The possible role of brain adenosine in acute ethanol-induced alteration in
      glucose utilization in the whole brain, as well as in the specific brain areas
      (cerebellum and brain stem), was investigated. Mice were killed 20-min
      postethanol, and the fresh tissue slices (300 microns) of brain and/or specific
      brain areas were incubated for 100 min in a 5.5 mM glucose medium in Warburg
      flasks using [6-(14)C]glucose as a tracer. Trapped 14CO2 was counted to estimate
      glucose utilization. Ethanol (2 g/kg, i.p.) markedly increased the glucose
      utilization in whole brain and in both motor areas of brain. Theophylline (50
      mg/kg, i.p.), an adenosine antagonist, significantly reduced ethanol-induced
      increase in glucose utilization in whole brain, as well as in brain areas.
      However, adenosine agonist N6-cyclohexyladenosine (CHA; 0.1 mg/kg, i.p.) on the
      contrary, significantly accentuated ethanol-induced increase in glucose
      utilization in these tissues that was nearly completely blocked by theophylline
      pretreatment. Theophylline alone did not produce any significant change in
      glucose utilization, whereas CHA alone (in vivo and in vitro) significantly
      increased glucose utilization, as well as ethanol-induced increase in glucose
      utilization in an additive manner. Relevant supportive data were obtained by
      experiments in which adenosine deaminase (ADA), p-sulfophenyltheophylline (8
      SPT), and CHA were administered in vitro to the slice preparations. Both ADA and
      8-SPT were effective in almost completely blocking the ethanol-induced increase
      in glucose utilization, whereas CHA further enhanced the ethanol-induced increase
      in glucose utilization in an additive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573809
TI  - Exposure of neonatal rats to alcohol by vapor inhalation demonstrates specificity
      of microcephaly and Purkinje cell loss but not astrogliosis.
AB  - The artificial rearing model (AR) of fetal alcohol syndrome (FAS) has been shown
      to induce several major pathologies in the early postnatal rat brain development:
      microcephaly, selective neuronal cell loss, and activation of astroglia in the
      neocortex. The purpose of this study was to determine whether these pathologies
      were specific to the action of alcohol or, in contrast, could result from
      confounds attributed to this model of FAS. For this purpose, the pathological
      effects of AR were compared with those of a vapor inhalation (VI) model of FAS.
      Our studies showed that the microcephaly that developed after exposure to
      periodic blood alcohol levels (BALs) of 300-350 mg% during postnatal days 4-9
      could be achieved by both AR and IV models of FAS, and thus is independent of the
      method of alcohol administration. In contrast, the gliosis measured by glial
      fibrillary acidic protein (GFAP) mRNA levels in cortex, as well as by
      immunohistochemical staining for GFAP, was found only in the AR-FAS model, but
      not in the VI model. However, the lack of gliosis in VI was apparently not due to
      a less intrusive intervention of alcohol, because VI exposure resulted in a
      reduction in Purkinje cell number comparable with that found after AR or
      intragastric intubation of alcohol. Based on these observations, we conclude that
      the activation of gliosis observed after AR is not a specific effect of alcohol,
      but rather is caused by an interaction of alcohol with as yet unidentified
      factors present in AR.

PMID- 7573812
TI  - Birch-pollen antigenic activity of settled dust in rural and urban homes.
AB  - Concentrations of birch-pollen antigens were measured in 10 homes in southwestern
      Finland, four in urban and six in rural areas. Dust samples were collected once a
      week with a vacuum cleaner equipped with a special collection device (ALK,
      Copenhagen) combined with an exchangeable glass microfiber filter in a filter
      dish. Control samples were taken from horizontal surfaces outdoors. All samples
      were analyzed by a modification of the IgG-ELISA procedure. The birch-pollen
      antigenic activity in indoor settled dust was lower than that in dust outdoors.
      The mean concentration of antigenic activity indoors peaked 3 weeks later than
      outdoors. The lag indicates that the most important means whereby antigens are
      carried indoors is via footwear and clothes, rather than, for instance,
      ventilation. Antigenic activity was still detected 2 months after the peak pollen
      period. As a source of antigens, both indoor and outdoor dust may be an important
      cause of pollen-allergy symptoms after the season.

PMID- 7573811
TI  - The role of cytokines and neuroendocrine hormones in cutaneous immunity and
      inflammation.

PMID- 7573813
TI  - Contralateral differences among biomarkers determined by a modified nasal lavage
      technique after unilateral antigen challenge.
AB  - The concentration of biomarkers from vessels and inflammatory cells in nasal
      lavage fluid reflects the degree of hyperresponsiveness in patients with allergic
      rhinitis. The lavage has usually been performed of both nasal cavities together
      after prewashings and administration of decongestants. To improve the technique,
      we introduced a modification involving lavage of the nasal cavities separately
      without any prewashings or decongestants. We challenged 20 rhinitic subjects
      sensitive to timothy unilaterally with timothy extract. In nasal lavages
      performed before, immediately after, and 6 h after the challenge, we determined
      the concentrations of albumin, histamine, bradykinin, TAME (N-alpha-tosyl-L
      arginine methyl ester)-esterase, and leukotriene C4 (LTC4). In eight subjects,
      the procedure was repeated 1 and 2 weeks later. After the challenge, albumin,
      bradykinin, TAME-esterase, and LTC4 in the nasal lavage fluid increased on the
      ipsilateral side but not on the contralateral side. Histamine did not increase
      after antigen challenge. After 6 h, the biomarkers were not increased. The
      concentrations of biomarkers did not differ between sides before the challenge
      and not between visits. Thus, the modified nasal lavage technique is reliable and
      improved compared to previous methods because it involves reproducible
      determinations of different biomarkers, and it is simple and easy to perform.

PMID- 7573814
TI  - Screening of atopic allergy in 5-year-old children--a comparison of the
      diagnostic properties of Phadiatop Paediatric and Phadiatop.
AB  - The ability of Phadiatop Paediatric (PP), Phadiatop (P), mixed-food RAST (MF),
      and the combination of P and MF to identify children with atopic allergy was
      evaluated among 193 children who had a family history of atopic disease, and who
      had an average age of 5 years. If atopy is defined as the presence of at least
      one positive skin prick test (> or = 2+) to common food and/or inhalant
      allergens, P had a sensitivity of 86%, a specificity of 94%, and an efficacy of
      92%. These figures were somewhat better than the results with PP. However, when P
      was combined with MF, the sensitivity increased to 89%, but at the expense of
      lowered specificity (83%) and efficacy (84%). If the tests were related only to
      clinical signs/symptoms of atopic disease, the sensitivity and efficacy were, at
      maximum, 63% and 81%, respectively. There was a discrepancy between the results
      of P and PP in 9% of the children. One explanation of this discrepancy may be
      that PP seems to be incapable of detecting children with respiratory allergies
      induced by pollens from birch and related trees. The results indicate that in 5-6
      year-old children P should be preferred to PP and to the combination of P and MF
      for atopy screening, at least in places where birch pollen is a common allergen.

PMID- 7573815
TI  - Gastric mucosal mast cells in atopic subjects.
AB  - Intragastral allergen provocation under endoscopic control (IPEC) allows direct
      observation of gastric mucosa reactions after contact with inhalant allergens
      that reach the stomach. We selected patients with proved atopy to Parietaria but
      without clinical and endoscopic signs of gastric disease, and we tested them with
      the specific inhalant allergen during IPEC, recording gastric macroscopic
      reaction and mucosal mast-cell changes in biopsy specimens. All atopic patients
      showed visible changes in gastric mucosa quantified as IPEC score. Mast-cell
      numbers detected in atopic patients (135.4 +/- 102.6/mm2 of stromal area) were
      significantly higher than in nonatopic subjects (59.8 +/- 25.4/mm2; P < 0.03) and
      were positively correlated to atopic IPEC score (P < 0.01). In addition, 6/12
      atopics who had both higher mast-cell counts and IPEC score showed an
      intraepithelial distribution of gastric mast cells which displayed
      ultrastructural features of partial degranulation. It is likely that changes
      observed in our patients with allergy to Parietaria reflect a subclinical
      activation of mast cells in the gastric mucosa.

PMID- 7573817
TI  - Substance P and alveolar macrophages: effects on oxidative metabolism and
      eicosanoid production.
AB  - The tachykinin substance P (SP) is present in lung sensory nerve endings and may
      be released after neurogenic stimulation. Its role in the pathogenesis of asthma
      is still unclear. Nevertheless, it may play a major role in airway neurogenic
      inflammation. Alveolar macrophages are the predominant cells of the airway space
      and are involved in various types of airway inflammation. We studied guinea pig
      alveolar macrophage response to SP and other related peptide (C- and N-terminal
      sequences, NK1-receptor agonist) stimulation. Alveolar guinea pig macrophages
      were recovered by bronchoalveolar lavage (BAL). Macrophage reactive oxygen
      intermediate (ROI) production was studied by luminol-dependent chemiluminescence
      with several concentrations of SP and related peptides. Eicosanoid synthesis
      after stimulation was evaluated by thin-layer chromatography (TLC) and enzyme
      linked immunosorbent assay (ELISA). SP, C-terminal sequence, and NK1-receptor
      agonist significantly increased ROI production by alveolar macrophages (P <
      0.01). NK1-agonist and C-terminal sequence modified arachidonic acid metabolism
      and induced a significant increase in prostaglandin (PG)D2 synthesis (211% and
      66%, respectively). We concluded that SP and related peptides directly affect
      guinea pig alveolar macrophages by inducing the production of inflammatory
      metabolites.

PMID- 7573816
TI  - IgE in stools as indicator of food sensitization.
AB  - The fragment of the Fc segment of IgE resistant to proteolytic enzymes was
      determined by a radioimmunologic method in fecal extracts from several groups of
      patients. IgEs remained undetectable in the 95 healthy subjects studied. IgEs
      were detected in 16/27 carriers of intestinal parasites (60%), with a mean of
      92.4 IU/g dry weight. IgEs were also detected in 236/312 food-sensitization
      patients, with the sensitizing foodstuffs being identified by searching for the
      specific IgEs in circulation (75%), with a mean of 63.9 IU/g dry weight. The
      simultaneous determination of alpha-1-antitrypsin in fecal extracts and in sera
      from 21 control subjects and 21 food-sensitization carriers demonstrated that
      extravasation of plasma proteins into the gut lumen cannot be responsible for the
      presence of IgE in stools. Testing for IgE in stools therefore appears to be a
      simple and economical means of identifying patients without parasites who present
      with food sensitization.

PMID- 7573819
TI  - Effect of allergen provocation on inflammatory cell profile and endothelin-like
      immunoreactivity in guinea-pig airways.
AB  - The effect of allergen challenge on the number of leucocytes and the
      concentration of endothelin 1-like immunoreactivity (ET-LI) in bronchoalveolar
      lavage fluid (BALF) was investigated in guinea-pigs sensitized to Ascaris suum.
      The animals were twice exposed to allergen aerosol. All animals responded to the
      second challenge with bronchoconstriction. Twelve hours later, a significant
      increase in the number of eosinophilic granulocytes in BALF, compared to
      unsensitized and unprovoked control animals, was noted. Twenty-four hours after
      provocation, there was also an elevation of ET-LI concentration and content of
      neutrophils. During the first day post-challenge, the ET-LI values were
      moderately correlated to the eosinophil levels. One week after challenge, the ET
      LI level and the neutrophil count did not differ from corresponding values in
      control animals whereas the number of eosinophils remained elevated. Pretreatment
      with dexamethasone before the second allergen challenge did not consistently
      affect the parameters studied during the first 24 h. Bronchoconstriction induced
      by carbachol aerosol affected significantly neither the ET-LI concentration nor
      the number of inflammatory cells in BALF. It is concluded that the allergen
      induced inflammation in the guinea-pig airways causes an elevation in the ET-LI
      concentration in BALF and that this is moderately correlated to the influx of
      eosinophils during the first 24 h.

PMID- 7573820
TI  - Hypersensitivity to cefuroxime with good tolerance to other betalactams.
AB  - A 60-year-old man developed an anaphylactic reaction immediately after
      administration of intramuscular sodium cefuroxime. By means of oral controlled
      challenge, the reaction was reproduced with a smaller dose of cefuroxime axetil.
      Cross-reactivity with other betalactam antibiotics was ruled out by in vivo
      tests. This case supports once again the relevance of the side-chain in
      betalactam allergy.

PMID- 7573818
TI  - Regulation of histamine release from human bronchoalveolar lavage mast cells by
      stem cell factor in several respiratory diseases.
AB  - We investigated the effects of stem cell factor (SCF) on histamine release (HR)
      from human bronchoalveolar lavage (BAL) mast cells. BAL cells were recovered from
      lavage performed in patients undergoing clinical bronchoscopy. SCF (0.02-20
      ng/ml), which is by itself a poor secretagogue (mean +/- SEM HR: 3.7 +/- 0.9%; n
      = 27), strongly enhanced HR induced by anti-IgE in a concentration-related
      manner. Significant potentiation began at 0.2 ng/ml (30 +/- 10%; p < 0.05; n =
      12) and reached a plateau at 2 ng/ml (40 +/- 10%; P < 0.01 at 2 ng/ml and 45 +/-
      10%; P < 0.01 at 20 ng/ml; n = 12). In contrast, SCF failed to enhance HR induced
      by calcium ionophore A23187. Among the BAL cell samples initially unresponsive to
      anti-IgE (55% of samples), 36% (10/28) were converted to responders if the cells
      were shortly preincubated with SCF. In 25% of samples (7/27), SCF (20 ng/ml)
      caused direct HR of 10 +/- 2.1%. The mast cells which released histamine when
      challenged with SCF also secreted higher levels of histamine in response to anti
      IgE and calcium ionophore than those nonresponsive to SCF. While interleukin (IL)
      3 and IL-5 (20 ng/ml) were unable to modulate immunologic HR, GM-CSF (20 ng/ml)
      produced significant potentiation (P < 0.05), which was, however, smaller than
      that observed with SCF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573821
TI  - Pharmacologic heterogeneity of human lung and colon cells: effect of terfenadine
      and cetirizine.
AB  - H1-blockers may have antiallergic properties which cause the blocking of
      eicosanoid release, and the effect of these drugs may differ according to the
      phenotype of mast cells. This study examined the ability of terfenadine and
      cetirizine to inhibit the release of arachidonic acid-derived mediators from
      human lung and colon cells. Dispersed cells were challenged with anti-IgE in the
      presence or absence of 10 microM of terfenadine or cetirizine, and the release of
      prostaglandin (PG)D2 and leukotriene (LT)C4/D4 was assessed by enzyme immunoassay
      (EIA). Terfenadine caused significant inhibition of both PGD2 and LTC4/D4 (49 +/-
      9 and 29 +/- 19%, respectively) from human lung cells but had a less marked
      effect on PGD2 release from human colon cells (21 +/- 9% for PGD2 and 18 +/- 9%
      for LTC4/D4). In contrast, although cetirizine caused significant inhibition of
      both mediators measured in lung cells (38 +/- 16% for PGD2 and 34 +/- 19% for
      LTC4), it did not cause any significant inhibition of either mediator from human
      colon cells. These findings suggest that H1-antagonists may have additional
      properties, and the differential effects of cetirizine on lung and colon tissue
      may indicate differences in mast cell phenotype.

PMID- 7573822
TI  - Peak expiratory flow variation and bronchial hyperresponsiveness in asthmatic
      children during periods of antigen avoidance and reexposure.
AB  - Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and
      their relationship with bronchial hyperresponsiveness (BHR) to methacholine
      (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust
      mite allergy, during successive periods of stay in a mite-free environment at
      high altitude (1756 m) and at their home at sea level. The children remained at
      the high altitude from October until the end of December; then they spent a 3
      week period at home and returned to high altitude residence in January. PEF was
      measured daily, in the morning and in the evening, during the 3 months' stay at
      high altitude and them for 10 days after the return in January. PC20 was assessed
      in 8/12 children, once a month from October to December, and at the return in
      January. Mean absolute PEF values did not change significantly throughout the
      study. From October to December, patients showed a significant decrease of mean
      %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3
      weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly
      worsened. The correlation between PC20 values and mean %PEF variation in the 2
      days before and after each methacholine test was r = -0.63 (P = 0.001). Our data
      suggest that there is a beneficial effect of a prolonged stay in a mite-free
      environment, on both PEF variability and BHR, also in asthmatic children with
      good pulmonary function. PEF variability and bronchial responsiveness to
      methacholine were significantly correlated also for small changes of the two
      variables.

PMID- 7573823
TI  - Increased levels of serum IgE in children of mothers with systemic lupus
      erythematosus.
AB  - Various allergic diseases have been described in patients with systemic lupus
      erythematosus (SLE). In the present study, we evaluated the prevalence of
      allergic disease and serum IgE levels in 36 children of 26 mothers with SLE. None
      of the subjects had any rheumatic symptoms. There was at least one type of
      allergic disease in 28 (78%) of the 36 children of mothers with SLE, as compared
      with 30% in Japanese control children (P < 0.01). The prevalence of atopic
      dermatitis and bronchial asthma was higher in children of mothers with SLE (64%
      and 28%) than in controls (19% and 9%) (P < 0.01, respectively). Fourteen of the
      36 subjects (39%) had higher levels of serum IgE than those of normal range for
      age-matched healthy Japanese children with no atopic family disease in the
      immediate family history, and these children had atopic disease. Among the 14
      children with high serum-IgE levels, seven had neither immediate nor remote
      family history of atopic disease, while the others had an immediate family
      history of atopic disease. We think that genetic factors may influence the
      presence of allergic disease in children of mothers with SLE, and that the
      increased serum IgE levels in children of SLE mothers with no allergic family
      history may be a part of subclinical immunologic abnormalities related to SLE.

PMID- 7573824
TI  - Is systematic preoperative screening for muscle relaxant and latex allergy
      advisable?
AB  - We investigated a female population prior to general anaesthesia, using skin
      prick tests with latex and muscle relaxants to appraise the validity and
      feasibility of a systematic preoperative screening for these substances.
      Anaesthetists performed skin tests, and positive and doubtful tests were checked
      in our allergy department. Of 114 patients, 42 had uninterpretable tests because
      of dermographism (28 patients) or suppression of skin reactivity (14 patients).
      Among the other 72, nine had a positive or doubtful test to latex, and seven a
      positive or doubtful test to one or more muscle relaxants. After checking, only
      four sensitizations to latex and one to muscle relaxant were confirmed. In
      conclusion, a systematic screening for latex and muscle relaxant allergy is not
      advisable. In contrast, screening for latex allergy in selected high-risk groups
      (spina bifida, health-care workers) is necessary.

PMID- 7573825
TI  - Latex allergens in glove-powdering slurries.
AB  - Exposure to airborne glove powder contaminated with latex allergens is known to
      provoke respiratory symptoms in latex-sensitized individuals. In the commonly
      used wet-powdering process in glove manufacturing, powder is applied by dipping
      gloves in a cornstarch suspension, a slurry. The slurry is a potential source of
      allergen contamination of the powder. The protein and latex allergen contents in
      five different slurries and in extracts from the corresponding latex gloves were
      measured using the BCA assay and the IgE antibody inhibition assay (EAI assay).
      Latex allergens were found in all slurries and gloves. No correlation between the
      values of protein contents and allergen contents was found. Wet powdering of
      gloves induces a risk of latex protein contamination of the cornstarch.

PMID- 7573826
TI  - Basic and practical aspects of recombinant allergens.

PMID- 7573827
TI  - Type III allergy skin testing. Position statement for EAACI Subcommittee on Skin
      Tests and Allergen Standardization.
AB  - Immune-complex-mediated hypersensitivity has been implicated in a small number of
      allergic respiratory conditions. These include EAA and ABPA. In addition, there
      is some evidence of type IV hypersensitivity in EAA and BFL, together with
      activation of complement via the alternative pathway (4, 8, 26). Positive
      immediate skin tests are now usually regarded as an essential criterion for the
      diagnosis of ABPA. These reflect the presence of antigen-specific IgE, but this
      test is not specific for ABPA, as other atopic subjects may also be sensitized to
      A. fumigatus without any evidence of the parenchymal features that are required
      to diagnose ABPA. For FL, skin tests with currently available antigens show poor
      discrimination between affected patients and exposed but healthy individuals.
      There is little evidence that vascular deposition of immune complexes in the skin
      contributes to the delayed skin responses in EAA, and skin tests in FL are not
      specific for type III hypersensitivity. Further refinement of methodology and
      antigen extracts may improve the specificity of skin tests in FL, but in many
      cases the aetiology of EAA is multifactorial and the true causative antigens may
      not have been identified. Therefore, the diagnosis of EAA remains based on
      history and clinical findings, supported by the presence of precipitins, and
      sometimes by bronchial biopsy and lavage appearances (25).

PMID- 7573828
TI  - Effects of "systemic" budesonide concentrations on in vitro allergen-induced
      activation of blood mononuclear cells isolated from asthmatic patients.
AB  - Blood levels of inhaled corticosteroids are significantly lower than those
      measured in the lung, but their concentration could still have anti-inflammatory
      effects. To determine whether budesonide, at concentrations similar to those
      obtained in blood after drug inhalation (10(-9) M), could downregulate the
      allergen-induced activation of mononuclear cells, we studied 21 atopic patients,
      sensitized to Dermatophagoides pteronyssinus (Der p). On blood mononuclear cells,
      isolated from these patients, incubated with Der p allergen extract and with or
      without budesonide, we evaluated: 1) the proliferative response of T cells; 2)
      the expression of two surface activation markers, the HLA-DR antigens and the
      interleukin (IL)-2 receptors; and 3) the release of cytokines known to modulate
      the allergic processes. Allergen-induced T-cell proliferation was associated with
      increased HLA-DR antigen and IL-2 receptor expression (P < 0.001), and with
      increased release of IL-2, interferon-gamma (IFN-gamma), IL-1 beta, tumor
      necrosis factor-alpha (TNF-alpha), and granulocyte/macrophage colony-stimulating
      factor (GM-CSF). The addition of budesonide at the beginning of the cell cultures
      induced a dose-dependent inhibition of T-cell proliferation, still significant (P
      < 0.05) at the lowest concentrations tested (10(-9) and 10(-10) M). A significant
      inhibitory effect on T-cell proliferation was also present when budesonide (10(
      9) M) was added to the cell cultures 3 or 5 days after the beginning of the cell
      cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573829
TI  - Grass pollen immunotherapy: efficacy and safety during a 4-year follow-up study.
AB  - Grass pollen immunotherapy is effective, although efficacy must be balanced
      against side-effects. In a double-blind, placebo-controlled trial of 40 adult
      patients with summer hay fever, immunotherapy with a depot grass pollen extract
      (Phleum pratense, Alutard SQ) reduced symptoms and medication requirements with
      an acceptable minimal level of side-effects (31). The original placebo group, as
      well as the actively treated group, have now received active immunotherapy in an
      open fashion for a further 3 years. An important question was whether continued
      injection treatment was accompanied by maintained clinical improvement. By
      analysis of diary symptoms, rescue medication, and visual analogue scores during
      the pollen season, we show that efficacy was maintained throughout the 3-4-year
      study period. Clinical improvement was accompanied by a sustained and marked
      decrease in immediate conjunctival allergen sensitivity and a further significant
      decrease in the size of the allergen-induced late cutaneous response. In
      contrast, an initial decrease in the allergen-induced immediate cutaneous
      response was not maintained at 3-4 years. Of the patients, 37/40 completed the
      first year, 33/40 the second year, and 32/40 the third year of treatment.
      Patients dropped out for reasons other than the outcome of immunotherapy. During
      a total of 2598 injections, five immediate systemic reactions were observed, all
      during the induction (not maintenance) phase, and all occurred within 10 min of
      injection and responded promptly to adrenaline. Grass pollen immunotherapy is
      effective and safe, provided it is performed on carefully selected patients by
      trained physicians with immediate access to resuscitative measures.

PMID- 7573831
TI  - Isolation and characterization of the 18-kDa major apple allergen and comparison
      with the major birch pollen allergen (Bet v I).
AB  - The major allergen from birch pollen, Bet v I, and the cross-reacting 18-kDa
      major allergen from Golden Delicious and Granny Smith applies were isolated by
      micropreparative SDS-PAGE followed by electroelution. In the case of apples,
      highly active, low-temperature extracts were used. The purity of the allergens
      was checked by analytic SDS-PAGE and immunoblotting with allergic patients' sera,
      as well as by N-terminal amino acid microsequencing, and the allergens were found
      to be very pure. The strong immunologic activity of the isolates was determined
      by the enzyme allergosorbent test (EAST) and EAST inhibition assays; this
      activity was, in the case of Bet v I, similar to that of a preparation obtained
      by monoclonal antibody affinity chromatography. The allergenic potency of Bet v I
      and of the cross-reactive apple allergen was determined by EAST inhibition and
      dose-related histamine release. With both assay systems, the allergenic
      reactivity of Bet v I was considerably higher than that of the major apple
      allergen. Furthermore, skin prick tests with the purified allergens and with
      whole allergenic extracts were performed on a group of 33 patients suffering from
      birch-pollen and apple hypersensitivity, and on a control group of 10 patients.
      The frequency of positive prick test results in the allergic patient group ranged
      from 73% for the major allergen from Golden Delicious apples to 97% with Bet v I
      and whole birch pollen extract, respectively. In contrast to our low-temperature
      extracts, commercial prick test solutions of four different manufacturers were
      found to be unreliable for the diagnosis of apple allergy. The skin test results
      again indicated the strong immunologic activity of the allergen isolates and the
      predominance of the major allergens in context with birch-pollen and apple
      hypersensitivity. Taken together, the results support the view that the 18-kDa
      major allergen represents most of the allergenicity of the the apple fruit, and
      that all allergenic epitopes of the apple proteins are present on Bet v I.

PMID- 7573830
TI  - Effects of loratadine on anti-IgE-induced inflammation, histamine release, and
      leukocyte recruitment in skin of atopics.
AB  - The aim of this study was to assess the ability of the H1-receptor antagonist
      loratadine to modify anti-IgE-induced cutaneous wheal-and-flare and late-phase
      reactions (WFR and LPR), as well as histamine release and leukocyte accumulation
      in skin chambers. For this purpose, 10 atopics with allergic rhinitis were
      entered into a double-blind crossover study in which they received either placebo
      or loratadine (20 mg/day orally) for 8 days separated by a 7-day washout period.
      Blisters were induced on both forearms on day 7 of each treatment period, and
      were unroofed on day 8 and covered with plastic skin chambers. Chamber fluids
      were collected during 7 h after 1-h incubation with anti-IgE or control IgG.
      Intradermal challenge with histamine and anti-IgE was performed at the same
      occasion. As compared to placebo treatment, loratadine inhibited the immediate
      WFRs to anti-IgE by 35% (wheal) and 65% (flare), respectively (P < 0.01), and
      corresponding reactions to histamine challenge by 50% and 70% (P < 0.001),
      respectively. Moreover, the initial phase (0-2 h) of the LPR induced by anti-IgE
      was attenuated by up to approximately 60% (P < 0.001) during loratadine
      treatment. Thereafter, no inhibition of the LPR was observed. The magnitude and
      time course of histamine release into skin chambers was virtually the same after
      loratadine and placebo treatment, with a peak during 0-1 h and a progressive
      decline during the following 2 h. Accumulation of alpha 2-macroglobulin,
      reflecting extravasation of large plasma proteins, also peaked during the first
      hour and was unaffected by loratadine during the 8-h observation period.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573832
TI  - Influence of the pH of the extraction medium on the composition of birch (Betula
      verrucosa) pollen extracts.
AB  - Extracts from birch (Betula verrucosa) pollen were prepared at different pH, with
      constant pH monitoring and adjustment to preset values in the range 5.5-8.5. The
      total protein content of these extracts was directly correlated with the pH.
      Coomassie brilliant blue-stained isoelectric focusing and SDS-PAGE gels and
      immunoblot analysis demonstrated qualitative differences: some proteins were lost
      while others appeared when pH was changed. At pH 8.5, formerly unknown birch
      pollen allergens were detected with pI 9, 9.10, and 9.30 by about 30% of birch
      pollen-sensitive sera. Birch pollen extracts prepared at a pH close to
      neutrality, namely, 6.5 and 7.5, showed the greatest protein and different
      allergen diversity. Thus, extraction pH values are necessary to analyze the whole
      pattern of allergenic components in an extract.

PMID- 7573833
TI  - Vineyard snail allergy possibly induced by sensitization to house-dust mite
      (Dermatophagoides pteronyssinus).
AB  - A female patient experienced a severe allergic reaction after consumption of
      vineyard snails. The patient proved to be sensitized to house-dust mite (HDM) and
      demonstrated a positive skin test and specific IgE to snail (Eobania vermiculata,
      Lofarma). The snail RAST was > 80% inhibited by HDM, whereas the mite RAST was <
      10% inhibited by snail extract. This is possibly another example of food allergy
      related to primary sensitization by an aeroallergen.

PMID- 7573834
TI  - Identification of important allergenic proteins in extracts of the granary weevil
      (Sitophilus granarius).
AB  - This paper describes the identification of important allergens from the granary
      weevil (Sitophilus granarius) (Sg). Sera from Danish bakers whose skin prick
      tests were positive to extracts of Sg were screened for IgE against Sg extracts.
      We found that 54% (n = 66) had elevated levels of IgE (RAST classes 1-3, by
      luminescent immunoassay) against whole-body extracts of Sg. The specificity of
      patient IgE was investigated in an inhibition-dot immunoblotting assay. IgE
      binding was inhibited in all sera but two, thus indicating that the patients' IgE
      was indeed specific for the Sg extract. In crossed immunoelectrophoresis, 23
      different proteins were identified. All RAST-positive sera were investigated in
      crossed radioimmuno-electrophoresis. At least 11 proteins in the Sg extract were
      capable of binding IgE. All individual sera reacted with at least four different
      proteins. The two most prominent allergens bound IgE from 88% and 100%,
      respectively, of the patients. These two are considered to be the most important
      allergens from Sg, and will be useful as markers in environmental immunochemical
      assays to detect allergens in samples from bakeries, grain stores, etc.

PMID- 7573835
TI  - Etiologic role of unapparent exposure in cat allergy.
AB  - To determine the importance of unnoticed exposure to cat, we studied 20 patients
      with a history of respiratory allergy. All the patients had a positive prick test
      to cat dander extract, and none of them kept cats as pets. The prick test was
      carried out with a dander extract from cat at a concentration of 100 BU/ml. The
      specific IgE was determined by the commercially available Pharmacia CAP System.
      We carried out a conjunctival challenge test. The concentration of Fel d 1 was
      quantified in dust samples from the patients' homes by a commercially available
      method. The patients were reassessed in order to establish a relation between
      exposure and symptoms, and concealed allergen sources. Sixteen patients showed
      significant levels of Fel d 1 in their homes (mean of 3.35 micrograms/g of dust).
      The conjunctival challenge test was positive in 15 patients. These patients
      showed an exposure mean of 0.4 microgram/g of dust. The mean levels of specific
      serum IgE were higher in those patients with a positive challenge than in those
      with a negative challenge (P = 0.0145). In nine reassessed patients, a relation
      was established between natural exposure and the onset of the symptoms. A
      possible hidden allergen source was established in 11 patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7573836
TI  - Survey of the allergic status of patients with bronchial asthma in Turkey: a
      multicenter study.
AB  - Patients diagnosed with bronchial asthma (BA) were prospectively enrolled to
      assess their allergen spectra and atopic status. The patients came from five
      major cities (Ankara, Izmir, Samsun, Elazig, and Adana) in different regions of
      Turkey. Atopic status, total IgE levels, and allergen spectra were determined in
      1149 patients and 210 controls who were spouses of the patients sharing the same
      environment but not consanguinity with the patients. Total IgE levels were
      significantly higher in the asthmatic patients. For both groups, total IgE levels
      were higher in both atopic and male subjects. Atopy rates were 42% in asthmatics
      and 26.1% in controls, declining notably by age in both groups. The most common
      allergen in both groups was house-dust mite (HDM), which was more frequently
      detected in coastal regions (Samsun, Izmir, and Adana). Allergen spectra of the
      patients included HDM, pollens, cockroach, pet animals, and molds in decreasing
      order of frequency. Phleum pratense and Artemisia vulgaris were the most common
      pollens in all regions, whereas Olea europaea was the most common in Izmir.
      Pollen sensitivity was least frequent in Elazig. For all of the regions, pet
      sensitivity was less common than, and mold sensitivity was comparable to, that of
      Western countries. In conclusion, BA patients in Turkey displayed significant
      differences in their allergen spectra and total IgE levels from control subjects
      and BA patients in Western countries.

PMID- 7573838
TI  - The role of the basophil in allergic inflammation.

PMID- 7573837
TI  - Assessment of sensitization to holm oak (Quercus ilex) pollen in the Merida area
      (Spain).
AB  - Sensitization to Quercus ilex (holm oak) was studied in 760 patients with
      clinically suspected sensitization to aeroallergens. Prick tests with commercial
      extracts of Q. ilex proved positive in 27 patients; none were monosensitive.
      Nasal and conjunctival provocation tests and specific IgE (RAST) performed with
      Q. ilex extracts in these patients were negative in all but one patient, who
      exhibited specific IgE titer (by RAST) of 7 PRU/ml (class 3). We conclude that Q.
      ilex pollen, though obtained in considerable quantities by our collector, does
      not cause allergies in our area.

PMID- 7573839
TI  - IgG1 and IgG4 antibody responses to the dust mite Lepidoglyphus destructor in a
      naturally exposed farming population.
AB  - The natural humoral immune response to the dust mite Lepidoglyphus destructor was
      assessed by comparing the IgG1 and IgG4 responses elicited in allergic (n = 44)
      and healthy (n = 16) individuals in a farming population chronically exposed to
      this allergen. With the aid of an immunoblotting technique and ELISA, the sera
      were analyzed for anti-L. destructor antibodies. While the majority of sera from
      the allergy group displayed several bands for both IgG1 and IgG4, the nonatopic
      healthy group was negative as analyzed in immunoblotting. When they were analyzed
      in ELISA, there was a significantly higher response in the allergy group than in
      the healthy group for IgG4, but not for IgG1. Taken together, these results imply
      that the immune system of individuals spared from allergic reactions to L.
      destructor not only lacks IgE antibodies but also seems largely to "ignore" these
      allergens/antigens despite exposure.

PMID- 7573840
TI  - Quantitation of major allergens in dust samples from urban populations collected
      in different seasons in two climatic areas of the Basque region (Spain).
AB  - We present the results of allergen content evaluation in 80 dust samples from 31
      homes of atopic patients from two climatic areas (humid and subhumid), collected
      in two seasons of the year (autumn and winter). Monoclonal antibody-based
      immunoassays were used to quantify Der p 1, Der f 1, Der 2, Lep d 1, and Fel d 1.
      The results were compared according to climate, season, and the type of
      sensitization (Pyroglyphidae mites, storage mites, or grass pollens). We
      underline the predominance of Dermatophagoides pteronyssinus (89% of samples)
      over D. farinae (16% of samples) in our environment. Der p 1 rates were higher in
      the humid area (Mann-Whitney P < 0.001), especially in the autumn (Wilcoxon P <
      0.05). Lep d 1 was detected in 23% of samples and Lep d 1 levels were higher in
      the homes of patients sensitized to storage mites (Mann-Whitney P < 0.05),
      whereas this allergen was not detected in the homes of pollen-allergic patients.
      Fel d 1 was detected in nine of the 31 homes (16% of samples) although there was
      a cat in only one home.

PMID- 7573841
TI  - Cry j 2, a major allergen of Japanese cedar pollen, shows polymethylgalacturonase
      activity.
AB  - We examined Cry j 2, a major allergen of Japanese cedar (Cryptomeria japonica)
      pollen, for polygalacturonase enzyme activity, since a nucleotide sequence of
      cDNA of Cry j 2 showed a significant homology with that of tomato
      polygalacturonase. Polygalacturonase is well known to depolymerize preferentially
      polygalacturonic acid (PGA) by hydrolysis. However, Cry j 2 did not act on PGA,
      but was found to depolymerize pectin and methylesterified PGA in a dose-dependent
      manner. The substrate specificity of Cry j 2 was different from that of
      polygalacturonase derived from Aspergillus niger. The depolymerizing activity of
      Cry j 2 reached a maximum at 50%-60% of methylesterification of PGA. In contrast,
      polygalacturonase showed its maximum activity of PGA, and the activity decreased
      as the degree of methylesterification increased. Interestingly, the pectin
      depolymerizing activity of Cry j 2 was due to a hydrolysis, but not a lyase,
      activity which splits the glycosidic bonds by beta-elimination, since no
      unsaturated uronides were found by measurement of absorbance at 235 nm in the
      reaction mixture. The enzyme activity was markedly inhibited by anti-Cry j 2
      antibodies. These results indicate that Cry j 2 probably has
      polymethylgalacturonase enzyme activity, as postulated by von Neukom in 1963,
      although existence of this activity has not yet been proven.

PMID- 7573842
TI  - Characterization of Chenopodiales (Amaranthus retroflexus, Chenopodium album,
      Kochia scoparia, Salsola pestifer) pollen allergens.
AB  - Pollen extracts of the four taxonomically related weeds, Amaranthus retroflexus
      (Ama r), Chenopodium album (Che a), Kochia scoparia (Koc s), and Salsola pestifer
      (S. kali) (Sal p), were characterized by various methods including crossed
      immunoelectrophoresis (CIE), crossed radioimmunoelectrophoresis (CRIE), and SDS
      PAGE immunoblotting. The allergen profiles were determined by CRIE and SDS-PAGE
      IgE immunoblotting. CRIE detected from one to four important allergens, while SDS
      showed up to four bands that bound IgE from a number of patient sera. CRIE and
      SDS-PAGE immunoblotting did not recognize the same number of important allergens
      in the individual weeds, and the number of allergens detected by the two methods
      differed considerably, suggesting that IgE-binding epitopes may be denatured
      during SDS-PAGE. However, it was possible to correlate the identity of some of
      the important allergens detected by CRIE and SDS-PAGE immunoblotting in all four
      weeds.

PMID- 7573843
TI  - The efficacy and tolerability of fluticasone propionate aqueous nasal spray in
      children with seasonal allergic rhinitis.
AB  - Fluticasone propionate aqueous nasal spray (FPANS) contains fluticasone
      propionate, which is a new topically active glucocorticoid with approximately
      twice the potency of belcomethasone dipropionate. In this European multicentre
      study, 143 children with seasonal allergic rhinitis were recruited: 47 received
      FPANS 100 micrograms once a day (od), 46 received FPANS 200 micrograms od, and 50
      patients received placebo od, for 4 weeks. Treatment efficacy was assessed using
      diary card nasal symptom scores for sneezing, rhinorrhoea, blockage and itching,
      and eye watering/irritation. Patients receiving FPANS 100 micrograms or FPANS 200
      micrograms demonstrated statistically significant improvements in median nasal
      symptom scores in all the symptoms recorded, when compared with placebo. There
      were no statistically significant differences between the FPANS 100 micrograms
      and FPANS 200 micrograms groups in improvement in nasal symptom scores. There was
      no effect on eye watering/irritation symptoms which could be attributed to either
      FPANS 100 micrograms or FPANS 200 micrograms when compared with placebo. Use of
      rescue antihistamine medication was significantly reduced in the FPANS 100
      micrograms group when compared with placebo. The adverse events profile was
      similar in all three treatment groups, and the events reported were generally
      mild and related to the patients' rhinitis.

PMID- 7573844
TI  - The first 20 minutes after a single dose of inhaled salmeterol in asthmatic
      children.
AB  - Very little is known as yet about the effect of salmeterol in pediatric asthma,
      so a trial was performed on children with mild asthma to compare salmeterol with
      salbutamol in terms of how quickly they took effect. The double-blind study
      involved 11 children (mean age 13.4 years) randomly assigned to inhale salmeterol
      50 micrograms, salbutamol 200 micrograms, or a placebo three times on alternate
      days. Peak expiratory flow (PEF), heart rate, and blood pressure were measured
      before and 5, 10, 15, and 20 min after administering the medication. With
      salbutamol, PEF was higher at 5 and 10 min, subsequently dropping off at 15 and
      20 min; with salmeterol, PEF was better at 10 and 20 min. Forced expiratory
      volume at 1 s (FEV1) measurements taken at the baseline and after 10 and 20 min
      revealed an important and consistent rise in values after salmeterol, whereas
      salbutamol was more effective after 10 min than after 20 min. No significant
      changes were recorded in heart rate or blood pressure after salbutamol; after
      salmeterol, there was a significant increase in heart rate after 5 min, but not
      at subsequent measurements. In conclusion, salmeterol begins to take effect
      already within 10 min of a single administration in asthmatic children, although
      the onset of its effect is slower than with salbutamol.

PMID- 7573845
TI  - Skin-prick-test-induced anaphylaxis.
AB  - An anaphylactic reaction occurred in a 57-year-old man after a prick by prick
      test with fresh kiwi and in a 29-year-old man after prick tests with some species
      of fish. Both patients had a history of anaphylaxis after ingestion of kiwi and
      fish, respectively. These cases suggest that, especially in patients with a
      history of anaphylaxis, all efforts should be made to minimize the risk of
      systemic reactions, and skin prick testing should be performed only in places
      equipped to treat anaphylaxis.

PMID- 7573846
TI  - First report of anaphylactic reaction after fig (Ficus carica) ingestion.
AB  - We report an anaphylactic reaction which occurred very shortly after ingestion of
      a fresh fig. The IgE-dependent mechanism was demonstrated on the basis of
      positivity of the prick test performed with fresh fig (Ficus carica) extract. In
      addition, we were able to detect specific IgE to the same extract in the serum.
      The patient did not demonstrate sensitization to other common allergens involved
      in respiratory and food allergies. However, detection of specific IgE to F.
      benjamina indicated a sensitization to weeping fig. The CAP F. benjamina was
      partially inhibited by preincubation of the serum with fig extract, suggesting
      that these two species of Ficus share some common allergens. In this context, the
      assumption can be made that weeping fig was responsible for the initial
      sensitization in this patient.

PMID- 7573847
TI  - House-dust mite ingestion can induce allergic intestinal syndrome.

PMID- 7573848
TI  - Interferon-gamma in the treatment of atopic dermatitis: influence on T-cell
      activation.
AB  - Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by
      various immunologic abnormalities. Its pathogenesis remains obscure and its
      treatment difficult. We have studied the efficacy of systemic recombinant human
      interferon-gamma (rhIFN-gamma) treatment (0.05 mg/m2 sc on 3 consecutive days,
      during 4 weeks) in 10 patients with severe AD. Marked clinical improvement was
      observed starting from the third week of treatment. Erythema, dryness, and
      lichenification were the most responsive symptoms. Serum immunoglobulin E and
      IgG4 levels did not change during treatment. Blood eosinophil count decreased
      only transiently at the end of the first and second series of injections (days 4
      and 11; P = 0.02). Patients with AD showed an increase in CD25-positive cells
      (11.0% vs 4.88%; P = 0.0001) as compared to 10 age-matched healthy controls.
      Moreover, in parallel with clinical improvement, a distinct decrease in CD25
      positive lymphocytes was observed on days 32 and 50 (P = 0.002 and P = 0.006,
      respectively). We suggest that in AD the beneficial effect of rhIFN-gamma might
      be related to the inhibition of excessive T-cell activation, perhaps of the
      subpopulations, producing interleukin (IL)-4 and IL-5.

PMID- 7573849
TI  - A double-blind, placebo-controlled comparison of sodium cromoglycate and
      ketotifen in the treatment of childhood asthma.
AB  - We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup
      (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo
      aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly
      allergic, moderately severe asthma. Treatments were added to current therapy
      (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily
      and syrups twice daily. The following results were significant at a level of 5%.
      At the final clinic visit, the changes from baseline in lung function favored
      sodium cromoglycate over the other treatments. During month 3, sodium
      cromoglycate was superior to ketotifen for night symptoms, morning tightness,
      daytime symptoms, and cough. Bronchodilator use decreased more with sodium
      cromoglycate than ketotifen. Patients' and clinicians' overall opinions of
      treatment effectiveness favored sodium cromoglycate over ketotifen and placebo.
      In these patients, sodium cromoglycate was both effective and superior to
      ketotifen.

PMID- 7573850
TI  - Characterization of the antibody response to a Haemophilus influenzae type b
      conjugate vaccine in children with recurrent lower respiratory tract infection.
AB  - Children with recurrent lower respiratory tract infection (RLRI) may respond
      poorly to polysaccharide antigens. To examine how such children respond to a
      polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI
      aged 8-69 months and 15 carefully age-matched healthy controls once with a
      Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses,
      total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of
      IgM, IgG, IgA, and IgG1-4 specificity were determined by ELISA. There were no
      significant differences between the two groups in any single total IgG subclass,
      but total IgG measured as the sum of all four subclasses was significantly lower
      in the children with RLRI than in the controls (P = 0.036). Before vaccination,
      the children with RLRI had significantly less IgG antipolysaccharide Hib antibody
      than the controls (P = 0.005), whereas 1 month later they had significantly more
      IgM antibody (P = 0.038). No other significant differences were found between the
      groups before or after immunization with respect to antipolysaccharide Hib
      antibodies. Since naturally occurring IgG antibodies are thought to be acquired
      partly as a consequence of antigenic stimulation on mucosal surfaces, we
      hypothesize that the low level of specific IgG found before immunization, as well
      as the low total IgG in the children with RLRI, may reflect an impaired ability
      to prime through mucosal surfaces. This is supported by our finding of an
      increased IgM response to Hib conjugate vaccine in these children, since this
      isotype predominates in the primary immune response, i.e., in the absence of
      immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573852
TI  - Statistical evaluation of nondetectable concentrations of IgE.

PMID- 7573851
TI  - Mite-specific IgE cannot be used as a surrogate for mite exposure.

PMID- 7573853
TI  - [Facial paralysis. Result of our electroneurographic studies].
AB  - The Electroneurography (ENoG) is one of the most employed electrodiagnostical
      techniques in the appraisal of acute facial palsies (AFP). Since 1989 we have to
      resort systematically to this exploration in our ENT-Department, which task
      previously was province of the Neurophysiological Service. On accordance with the
      exam's results we then express the prognostic, regarding the seriousness of the
      paralysis, and so settle the indication or the abstention for the rehabilitative
      treatment. We report here a review of 92 APF's seen during 1990 and consider
      their evolutive course which is compared with that in advance supposed to be. In
      the light of our final results we venture to say that ENoG, in our hands, is a
      good prognostical indicator and also is an adequate standard of judgement in
      order to recommend the rehabilitative management of AFP.

PMID- 7573854
TI  - [Epidemic outbreak of herpes zoster oticus (Ramsay-Hunt syndrome)].
AB  - In this paper are reported 5 cases of herpes zoster oticus diagnosed in our
      surroundings, all of them presented independently, in a two weeks term.
      Discussion of the disease's etiopathogeny besides the possibility of its
      spreading as outbreaks.

PMID- 7573855
TI  - [Supraglottic carcinoma].
AB  - We present the follow-up and end results of 98 horizontal supraglottic
      laryngectomies done for treatment of supraglottic carcinomata. Both functional
      and oncologic outcome as well the complications and 5-year survival of these
      laryngectomies are considered. We conclude that this surgical technique is a
      suitable one for the larger part of supraglottic carcinomas.

PMID- 7573856
TI  - [Recording of evoked otoacoustic emissions in adult normal hearing population.
      Percentile of normalcy].
AB  - Evoked otoacustic emissions recording hold some promise as a fast objective and
      non-invasive audiological procedure to study the cochlea at the outer hair cell
      level. This study has been made in 100 voluntary normal hearing adults. We
      evaluate the auditory system by means of evoked otoacustic emissions with a non
      linear click. This report resumes methods and results in these normal grown-up
      ears.

PMID- 7573857
TI  - [Tonsillar microsurgery by bipolar dissection].
AB  - The 66 amygdalectomies done by the AA. under general anesthesia and tracheal
      intubation are considered in two groups. The first one was composed by 32
      patients operated following a dissection and coagulation procedure with the aid
      of a bipolar forceps and under microscopical magnification. The second group, 34
      cases, underwent the classical procedure with ligature of the bleeding vessels.
      The usage of the bipolar forceps procure lesser loss of blood as compared with
      the dissection-ligature procedure. On the contrary, the bipolar clip method
      showed and increased postoperative pain and also the lagging of the swallow
      function. Both techniques presented with very similar complications (bleeding,
      edema, loca infection).

PMID- 7573858
TI  - [Our experience in the management of parapharyngeal tumors].
AB  - The rate of occurrence of neoplasma arising from the parapharyngeal space is
      scarce, about 0.5 percent of neck and face tumors. In the paper is reported our
      10-year experience on its clinical diagnosis and therapeutical management as
      well. We have found 13 percent (3/23) malignancies and 87 percent (20/30) benign
      growth. 35 percent were paragangliomas and 22 percent represent salivary tumors.
      Diagnostic procedures, ways of approach and surgical complications are
      considered.

PMID- 7573859
TI  - [Calcifying odontogenic epithelial tumor (Pindborg's tumor). Review of a case
      with maxillary localization].
AB  - We report a case of maxillary sitting of a calcifying odontogenic epithelial
      tumor (Pindborg's tumor). It is a benign tumor with similar microscopical
      findings with the ameloblastoma although its natural evolution is different. The
      tumor has an actodermal odontogenic origin. The stem cell from which it develops
      and its growth stimulus are unknown. Although the intermediary stratum of the
      enamel producing organ has been incriminated. A swelling of the maxillae or a
      casual finding--as the case reported--are the most common manifestations at
      beginning of these cases. The differential diagnosis depends on the radiological
      pattern we may find. Various surgical procedures may be considered optional. It
      could vary from enucleation to complete resection of the affected structure.
      Aggressive surgery is not indicated.

PMID- 7573860
TI  - [Tonsillolithiasis].
AB  - A 43-year-old female patient complaining with odynophagy since a month and a half
      without response to the medical treatment is presented. The pharynx exam showed
      an asymmetric swelling in the right tonsillar surface and the radiology provided
      evidence of calcareous concretions as responsible cause of the picture.

PMID- 7573861
TI  - [Solitary nasal plasmocytoma].
AB  - Report of the case of one patient diagnosed of a nasal extramedullary solitary
      plasmacytoma, starting as an suppurated panophtalmia. Biopsy of the mass inside
      the nose led to diagnosis. Comments about the difficulties of histopathological
      differential diagnosis, underlying the need to rule out any other systemic
      process (multiple myeloma). The subject was treated with inductive chemotherapy
      and radiotherapy, being free of the illness after 4 years follow up.

PMID- 7573862
TI  - Assessment and control of pain in children.

PMID- 7573864
TI  - The effect of nitrous oxide on the performance of psychomotor tests. A dose
      response study.
AB  - The effect of different nitrous oxide concentrations on the performance of
      psychomotor tests (inspection time, tapping frequency, critical flicker fusion,
      picture memory and time sense) was investigated in seven healthy volunteers. The
      results show a dose-related impairment of memory, a reduction in tapping
      frequency and an increase in inspection time. A paradoxical increase in critical
      flicker-fusion threshold was observed. There was no effect on critical fusion
      flicker threshold or time sense. Recovery was incomplete for memory tests
      performed 20 min after withdrawal of nitrous oxide. Subjective effects persisted
      for several hours.

PMID- 7573863
TI  - Difficult direct laryngoscopy in patients with cervical spine disease.
AB  - Two hundred and fifty three patients were examined before surgery for cervical
      spine disease. The grade of glottic visibility was determined at direct
      laryngoscopy, using the classification proposed by Cormack and Lehane. The
      overall prevalence of difficulty (grades 3 and 4) was 20%. Patients with disease
      that includes the occipito-atlanto-axial complex have a higher prevalence of
      difficulty than those with disease below the axis vertebra. Occipito-atlanto
      axial disease is associated with poor mandibular protrusion. The best single
      predictor of difficulty was reduced separation of the posterior elements of the
      first and second cervical vertebrae on lateral radiographs. The Mallampati
      examination was the best single predictor on physical examination. The Mallampati
      may be an indicator of poor cranio-cervical extension. Difficulty was rare in
      patients with class A mandibular protrusion, and invariable in patients with
      class C protrusion.

PMID- 7573866
TI  - Cardiac function during orthotopic liver transplantation with venovenous bypass.
AB  - We have studied the effect of varying the flow of a venovenous bypass system
      during orthotopic liver transplantation. During these manipulations, central
      venous (n = 9) or pulmonary artery occlusion (n = 9) pressures were kept
      constant. There was no change in right ventricular systolic or diastolic function
      in either group, suggesting that any conformational change of the ventricle
      during bypass is not of functional significance. The extrapolated volume loading
      required to compensate for the absence of bypass is of the order of 3000 ml.

PMID- 7573867
TI  - The clinical pharmacology of doxacurium in young adults and in elderly patients.
AB  - Neuromuscular blockade induced by doxacurium 30 micrograms.kg-1 was compared in
      21 young (18-55 years) and 17 elderly (65-85 years) patients. Anaesthesia was
      induced with thiopentone and maintained with fentanyl, nitrous oxide in oxygen
      and isoflurane. Neuromuscular blockade was measured electromyographically (Datex
      Relaxograph) at the adductor pollicis using train-of-four stimuli at 20 s
      intervals. The depth of maximum neuromuscular blockade was similar in young and
      elderly patients (median 100% compared to 96%). However, the onset was
      significantly slower in the elderly: their mean (SD) time to 90% suppression of
      the first response of the train-of-four was 7.7 (1.8) min compared to 5.7 (1.7)
      min in the young (p = 0.002). Four min after doxacurium, the conditions for
      tracheal intubation were significantly poorer in the elderly (p < 0.001). Mean
      (SD) recovery of first response of the train-of-four to 25% of control was
      unaffected by age: young 79.0 (41.6) min; elderly 66.2 (32.1) min (p > 0.05).
      When the first response had reached 25% of control, neuromuscular blockade was
      antagonised with neostigmine 60 micrograms.kg-1. The mean time to first response
      to 90% of control was similar in the young and the elderly patients (9.1 min
      compared to 10.4 min). Recovery of the train-of-four ratio to 0.7 was
      significantly slower in the elderly: mean (SD) 17.1 (10.6) min compared to 10.1
      (7.0) min (p = 0.03). Doxacurium was associated with clinically insignificant
      haemodynamic changes in both groups.

PMID- 7573868
TI  - A prospective study of anaesthesia for quinsy tonsillectomy.
AB  - A prospective study of 50 adult quinsy tonsillectomy anaesthetics was performed.
      There were no significant anaesthetic or surgical complications and the mean
      intra-operative blood loss was 176 ml. The Mallampati score did not correlate
      with the Cormack and Lehane glottic view and there were no difficult intubations.
      Pre-operative trismus resolved completely during induction in 77.4% of cases. We
      concluded that the Mallampati grading system is not applicable in quinsies and in
      cases with palatopharyngeal arch distortion, that trismus in quinsies is due to
      muscle spasm and resolves completely during induction in most cases and that pre
      anaesthetic drainage of the abscess together with rehydration and antibiotics are
      important contributing factors to safe anaesthesia for quinsy.

PMID- 7573865
TI  - Effect of general anaesthesia and surgery on neutrophil function.
AB  - The effects of general anaesthesia and surgical trauma on neutrophil function
      were studied in 60 female ASA 1 and 2 patients undergoing anaesthesia for
      gynaecological surgery. Patients were divided into three groups depending on the
      degree of trauma and duration of surgery. Group 1 (n = 15) were patients for
      dilatation and curettage (minor surgical trauma) and were given 2% halothane.
      Group 2 (n = 30) had laparoscopic surgery (moderate surgical trauma) and received
      either 0.5% halothane or 1% enflurane. Group 3 (n = 15) were those having
      hysterectomy (major surgical trauma) and received 0.5% halothane for a longer
      duration. Venous samples were taken 30 min before anaesthesia (control value), 10
      min after induction of anaesthesia, 10 min after the start of surgery, 30 min
      after the end of anaesthesia and 24 h later. Phagocytic index, nitroblue
      tetrazolium reduction test, total leucocyte count, and differential leucocyte
      counts were performed on each sample. Data were analysed by paired t-test to
      compare findings in the same patient and by unpaired t-test for differences
      between groups. Anaesthesia with halothane 0.5% to 2% caused a dose-related
      depressant effect on leucocyte function which reversed. Enflurane 1% on the other
      hand caused significantly greater depression of leucocyte function compared with
      0.5% halothane which persisted during the recovery period and recovered on the
      first postoperative day. Total leucocyte counts also showed a fivefold increase
      in the major surgery groups.

PMID- 7573869
TI  - The effect of different end-tidal volatile agent and carbon dioxide
      concentrations upon the incidence of postoperative shivering.
AB  - Sixty patients (47 female) undergoing surgical excision of three or more wisdom
      teeth were randomly allocated into three groups with differing end-tidal carbon
      dioxide and volatile agent concentrations during maintenance of anaesthesia. The
      anaesthetic techniques employed were identical in all other respects. All
      patients were observed for 10 min after arrival in the recovery area to assess
      the presence and severity of shivering, axillary temperature and oxygen
      saturation. There were no significant differences in axillary temperatures
      between groups or between shivering and non-shivering patients, although there
      was a significant difference (p = 0.001) in duration of anaesthesia between
      shivering and non-shivering patients. There was no significant difference between
      groups with respect to the incidence of shivering (p = 0.96).

PMID- 7573870
TI  - An evaluation of the Universal PAC and Oxford Miniature Vaporizers for paediatric
      field anaesthesia.
AB  - A laboratory study has demonstrated that the Universal PAC and Oxford Miniature
      Vaporizers can be used for paediatric anaesthesia in drawover mode at varying
      ambient temperatures. Changes in tidal volume have minimal effect on the
      delivered concentration of halothane from either vaporizer but varying ambient
      temperature significantly affects the output of the Oxford Miniature Vaporizer.
      The Oxford performs well in continuous flow mode, which is of particular use for
      T-piece anaesthesia, whereas the Universal PAC does not perform adequately in
      this way.

PMID- 7573871
TI  - Problems of oxygenation and oxygen transport during haemorrhage. 1964.

PMID- 7573872
TI  - Toxic epidermal necrolysis with adult respiratory distress syndrome.
AB  - A severe case of drug-induced toxic epidermal necrolysis is described in which
      the adult respiratory distress syndrome developed, requiring a prolonged period
      of mechanical ventilation and intensive care. The importance of early transfer to
      the intensive care unit for monitoring and prompt treatment of complications of
      this rare condition is emphasised.

PMID- 7573873
TI  - Delayed amniotic fluid embolism following caesarean section under spinal
      anaesthesia.
AB  - A case of amniotic fluid embolus is described with an acute onset occurring 90
      min after surgical delivery in a mildly pre-eclamptic primigravida undergoing
      Caesarean section for a breech presentation. Severe disseminated intravascular
      coagulation and massive postpartum haemorrhage were corrected and she went on to
      make a full recovery. The pathophysiology of amniotic fluid embolism is discussed
      and new diagnostic tests are reviewed. It is suggested that in this patient an
      amniotic fluid collection in dilated uterine veins was mobilised as venous tone
      returned following the offset of spinal anaesthesia and sympathetic blockade.

PMID- 7573874
TI  - Anaesthesia for caesarean section in a patient with Klippel-Feil syndrome. The
      use of a microspinal catheter.
AB  - A 34-year-old woman with severe kyphoscoliosis, an immobile cervical spine, and
      short stature due to the Klippel-Feil syndrome presented for elective Caesarean
      section. She expressed a strong desire to remain awake during the procedure. We
      chose a technique using a spinal microcatheter to provide spinal anaesthesia on
      the basis that incremental control of the dose of bupivacaine would reduce the
      risk of 'high' block. Awake inspection of the larynx was performed as a
      precaution in the event of respiratory embarrassment. A total of 6.25 mg heavy
      bupivacaine, 7.5 mg plain bupivacaine, and 10 micrograms fentanyl were
      administered over 20 min. This provided anaesthesia up to T5 without significant
      effects on respiratory or cardiovascular function. The patient was successfully
      delivered of a healthy boy.

PMID- 7573875
TI  - Peri-operative assessment of glomerular permeability.
AB  - Surgical trauma may provoke an increase in glomerular permeability.
      Microalbuminuria is a subclinical increase in urinary albumin ranging from 20 to
      300 mg..-1. This cannot be measured with routine laboratory tests and is
      estimated by radioimmunoassay. It has been proposed that microalbuminuria, an
      expression of increased glomerular permeability, serves to reflect a generalised
      increase in systemic vascular permeability. In this study the degree of
      microalbuminuria (expressed as microalbuminuria/creatinine ratio to correct for
      dilutional changes) has been measured in two groups of patients undergoing either
      videolaparoscopic surgery (group A) or conventional, open, abdominal surgery
      (group B). The anaesthetic technique was standardised and the duration of surgery
      similar in the two groups. A significant increase (p < 0.01) in the
      microalbuminuria/urinary creatinine ratio occurred in patients undergoing open
      abdominal surgery (group B). This alteration appeared 2 h after surgery but had
      disappeared 24 h after the end of the operation. During surgery, there was a
      direct relationship between glomerular permeability and the severity of the
      surgical insult.

PMID- 7573876
TI  - Paravertebral blockade. Failure rate and complications.
AB  - The failure rate and complications were studied prospectively in 367 paediatric
      and adult patients who had received a thoracic or lumbar paravertebral block. The
      overall failure rate was 10.1%; adults 10.7%; children 6.2%. The frequency of
      complications were: hypotension: 4.6%; vascular puncture: 3.8%; pleural puncture:
      1.1%; pneumothorax: 0.5%. Since these results are similar to those found with
      alternative methods, e.g. epidural, intrapleural and intercostal blocks,
      paravertebral block can be recommended as an effective, safe technique for
      unilateral analgesia in both adults and children.

PMID- 7573878
TI  - Correct positioning of the epiglottis for application of the Brain laryngeal mask
      airway.
AB  - Positioning of the epiglottis when the Brain laryngeal mask airway is in place
      was studied in 20 adult patients, using a new technique of insertion. The
      laryngeal mask was inserted when the anterior displacement of the mandible
      extended the epiglottis, thereby the providing an excellent airway in all
      patients. In 10 out of these 20 patients, the conventional technique of insertion
      revealed an incomplete extension of the epiglottis, and inadequate opening of the
      laryngeal inlet. It was concluded that the anterior displacement of the mandible
      during insertion of the laryngeal mask enhances the opening of the larynx, the
      result being an excellent airway.

PMID- 7573879
TI  - The effect of a combination of rectal diclofenac and caudal bupivacaine on
      postoperative analgesia in children.
AB  - Both caudal anaesthesia and non-steroidal anti-inflammatory drugs have been used
      in the management of postoperative pain in children. The aim of the present study
      was to evaluate the combination of caudal analgesia and rectally administered
      diclofenac in the treatment of pain following minor surgery in children. Thirty
      nine, ASA grade 1 or 2, children undergoing inguinal or penoscrotal surgery were
      randomly assigned to receive either a caudal block using 0.125% bupivacaine with
      adrenaline or a similar caudal block in combination with rectally administered
      diclofenac 1 mg.kg-1. Children given a caudal block alone were more likely to
      need analgesia in the first 24 h postoperatively. It would appear that the
      combination of a caudal block and rectal diclofenac in children undergoing minor
      lower abdominal surgery reduces the need for subsequent analgesia.

PMID- 7573880
TI  - Mortality prediction algorithm and intensive care.

PMID- 7573881
TI  - Drugs in status epilepticus.

PMID- 7573877
TI  - An assessment of morphine requirement after wisdom tooth extraction under general
      anaesthesia.
AB  - The use of morphine delivered by a patient-controlled analgesia system was
      studied in 20 patients who had undergone surgical extraction of three or four
      wisdom teeth as inpatients. Whilst 64.3% of the patient requests were made in the
      first 8 postoperative hours, use of the system continued throughout the night in
      the majority of patients. The implications for analgesic regimens in day-case
      surgery are discussed.

PMID- 7573882
TI  - Consistency of the ASA classification.

PMID- 7573883
TI  - Consistency of the ASA classification.

PMID- 7573884
TI  - Laryngospasm following extubation in children.

PMID- 7573886
TI  - Disposable PCA devices: the lockout interval may not be what it seems.

PMID- 7573887
TI  - A hazard with the Abbott Provider 5500.

PMID- 7573885
TI  - Diclofenac and post-tonsillectomy haemorrhage.

PMID- 7573889
TI  - Safety of lignocaine test dose to detect intravenous injection.

PMID- 7573888
TI  - Defective intravenous cannula.

PMID- 7573890
TI  - An avoidable cause of inadvertent dural puncture.

PMID- 7573891
TI  - Equipment failure during epidural catheter placement.

PMID- 7573892
TI  - Movement and pulse oximetry.

PMID- 7573894
TI  - Microlaryngeal surgery without a tracheal tube.

PMID- 7573893
TI  - Pressure reducing valve prevents barotrauma during jet ventilation for
      microlaryngeal surgery.

PMID- 7573895
TI  - Yet another simple connector for transtracheal ventilation.

PMID- 7573896
TI  - Paediatric capnography.

PMID- 7573897
TI  - Are the two long prongs of the Mallinckrodt double-lumen endobronchial tube
      necessary?

PMID- 7573898
TI  - Guidewires and central venous catheters.

PMID- 7573899
TI  - Transporting volatile agents in hot climates.

PMID- 7573900
TI  - [Quality comparison of modified neurolept-, balanced and intravenous anesthesia.
      1. Study design and patient analysis of the Krefelder study 1992].
AB  - The choice of appropriate anaesthesia in a more or less seriously ill patient
      requires detailed information on the risk and tolerance of each specific
      anaesthetic regimen. The objective of this prospective, randomised clinical trial
      was to test the hypothesis that three regimens of general anaesthesia--neurolept
      (NLA), balanced (BAL), and intravenous propofol anaesthesia (IVA)--differ with
      regard to safety and comfort. The criteria for the intraoperative safety and
      postoperative comfort of the patients were the incidents, events and
      complications (IEC) that required medical treatment as well as the evaluation of
      postoperative complaints by the patients according to the IEC list and patient
      questionnaires of the German Society of Anaesthesia and Critical Care Medicine
      (DGAI). METHODS. The study duration was about 4 months, from January to April
      1992. During this period the patients of all nine operative departments of the
      hospital received strictly randomised NLA, BAL, or IVA. Patients who had regional
      anaesthesia or were not capable of understanding the German language, were nonco
      operative, or were seriously ill (ASA class IV to V) as well as children under 18
      years of age did not participate in the study. All eligible patients provided
      their informed consent. ANAESTHESIA. For premedication 10 mg chlorazepate was
      administered the night before and on the day of surgery. Anaesthesia was
      conducted under normoventilation using a mixture of 70% nitrous oxide and 30%
      oxygen. NLA patients were induced intravenously with 0.2 mg/kg body weight
      etomidate and received 0.005 mg/kg fentanyl and 0.07 mg/kg droperidol before the
      start of surgery. The repetition dose was 0.2 mg fentanyl and 2.5 mg droperidol.
      In the BAL patients the dose of fentanyl and droperidol was reduced to 50% due to
      the addition of isoflurane up to 1 vol. %. IVA patients received 2 mg/kg propofol
      over 3 min followed by an infusion of 3-5 mg/kg per hour together with 0.2 mg
      fentanyl/h. Neuromuscular blockade was accomplished with vecuronium 0.1 mg/kg. If
      the blood pressure and heart rate increased by more than 20% of preoperative
      values, analgesia was reinforced by an additional fentanyl dose. Anaesthesia was
      subsequently enhanced by increasing the neurolept/propofol/isoflurane dose by up
      to 50%. DATA COLLECTION. The following parameters were registered: patients'
      personal data and physical condition according to ASA classification; the grade
      of risk according to the Munich risk checklist; the frequency of IEC during
      surgery; the patients' permanent medications; postanaesthetic vigilance and
      recovery; the acceptance of the assigned anaesthetic by the physician; the cost
      of the anaesthetic used; and pre- and post-operative complaints as well as the
      assessment of anaesthesia by the patient. The statistical evaluation was
      performed using the chi-square test. RESULTS. A total of 1,346 patients were
      enrolled in the study; 28 (2%) were excluded because the treatment protocol was
      changed by the anaesthesiologist. Seventy per cent were recruited from general,
      gynaecologic, or otorhinolaryngologic surgery. The three anaesthetic regimens
      (NLA, BAL, and IVA) were used in other departments with the same frequency with
      the exception of ophthalmology and urology (P > 0.1) (Fig. 1). Of the 1,318
      eligible patients, 443 received NLA, 443 BAL, and 432 IVA (P = 0.8). The
      distribution of the various parameters was surprisingly similar among the three
      groups: the average age was 50 years (P = 0.91), body weight 71 kg (P = 0.33),
      reference or initial blood pressure 130/80 mm Hg (P = 0.36), average time of
      anaesthesia 103 min (P = 0.82), and all had the same risk score (P = 0.42). Sixty
      per cent were female. An average of 85% of the 18- to 89-year-old patients were
      considered to be healthy according to the ASA risk classification (P = 0.42).
      However, on applying the Munich risk checklist the average number of healthy
      individuals was 5% to 10% lower than that of the ASA risk classification.

PMID- 7573901
TI  - [Effects of serotonin 2 receptor agonists on skeletal muscle preparations in
      patients with a disposition toward malignant hyperthermia].
AB  - In pigs genetically susceptible to malignant hyperthermia (MH), it has been shown
      that serotonin (5-HT2) receptor agonists can induce MH and "psychotic" behaviour.
      Both can be prevented by 5-HT2 receptor antagonists. Furthermore, free levels of
      serotonin in plasma increased concomitantly with clinical and laboratory
      parameters during halothane-induced MH in pigs. In this study the in vitro
      effects of the 5-HT2 receptor agonist1-(2,5-dimethoxy-4-iodophenyl)-2-amino
      propane (DOI) were investigated in muscle specimens of MH-susceptible (MHS) and
      normal (MHN) patients. METHODS. Muscle biopsies were obtained from 37 patients
      aged 5-69 years (23.6 +/- 5.3 years) with clinical suspicion for MH. The patients
      were first classified as MHS, MHN or MHE (MH equivocal) by the in vitro
      contracture test (IVCT) according to the European MH protocol. After MH
      classification, surplus muscle specimens were subjected to the DOI study. DOI was
      added to the organ bath in a concentration of 0.02 mmol/l. The in vitro effects
      on contracture development and muscle twitch were observed for 120 min. RESULTS.
      Muscle specimens of all patients developed contractures after administration of
      DOI. However, DOI produced an earlier development of contracture in MHS (17.0 +/-
      1.8 min; n = 17) than in MHN (64.7 +/- 5.9 min; n = 15) muscles. In MHS muscles,
      contractures were more distinct than in MHN muscles; at the end of the
      experiment, contractures had reached a maximum of 12.5 +/- 0.9 mN in MHS and 5.1
      +/- 0.7 mN in MHN muscles. Muscle twitch following DOI administration was reduced
      significantly in both MHS and MHN muscles. The results of four MHE muscles were
      comparable with MHS. CONCLUSION. The present study supports the assumption that
      an altered serotonin system might be involved in the development of MH. In
      further studies it should investigated whether 5-HT2 receptors of skeletal
      muscles from MHS subjects are disordered in function or structure. 5-HT2 receptor
      agonists should be considered as MH-triggering agents.

PMID- 7573902
TI  - [Tamm-Horsfall protein, alpha-1- and beta-2-microglobulin as kidney function
      markers in heart surgery].
AB  - After cardiac surgery, transient renal dysfunction often occurs. Regional
      differentiation of these processes is possible only using invasive techniques,
      including renal biopsy. Approximately 30 different plasma protein components have
      been identified in the urine of healthy individuals by means of qualitative and
      quantitative immunochemical methods. The detection of microalbuminuria has high
      diagnostic relevance for the early diagnosis of renal damage at a reversible
      stage. One typical urinary protein is Tamm-Horsfall protein (THp). After
      histochemical staining of human kidney sections, activity is seen in the loop of
      Henle and initial distal tubule. The assay of alpha-1 microglobulin (MG) in urine
      is considered one of the most efficient laboratory parameters for the diagnosis
      of tubular lesions. Serum concentrations of alpha-1 MG are less dependent on
      extrarenal changes than are those of other low-molecular-weight proteins. beta-2
      MG is also one of the standards used in recent years for diagnostic relevance.
      Urinary albumin excretion, normally less than 30 mg per day, sometimes increases
      after glomerular damage. Some renal function tests are used daily in many
      intensive care units, e.g. creatinine clearance (CCr) or urea and sodium
      excretion. Renal dysfunction should, however, be further examined to localise
      regional damage and to seek new clinical standards in addition to the
      conventional tests. METHODS. After obtaining the agreement of the local ethics
      committee, 30 patients were divided into two groups of 15 each: group I without
      renal dysfunction and CCr more than 60 ml/min; and group II with CCr below 60
      ml/min. THp and alpha-1 MG were measured pre- and postoperatively after open
      heart surgery with the ELISA and beta-2 MG with the nephelometric technique.
      These parameters were compared with clinical standards such as albumin excretion,
      blood urea nitrogen (BUN), urea clearance, and fractional sodium excretion.
      RESULTS. The CCr did not change in group I from the pre- to postoperative period
      (81.5 to 85.1 and 91.4 ml/min), nor did excretion of THp (20.1 to 25.0 and 24.8
      mg/day), correlation r = 0.7; P < 0.001). The elimination of alpha-1 and beta-2
      MG was significantly higher in the postoperative period in this group (alpha-1:
      7.2 to 44.1 and 100.6 mg/day; beta-2: 0.3 to 2.1 and 3.2 mg/day). In group II CCr
      showed pathological values (36.8 to 31.1 and 36.3 ml/min), as did simultaneous
      THp (13.5 to 9.7 and 12.7 mg/day). alpha-1 and beta-2 MG values became more
      pathological in the postoperative period than in group I (alpha-1: 32.8 to 113.9
      and 198.5 mg/day; beta-2: 0.7 to 5.8 and 16.9 mg/day). DISCUSSION. Measurement of
      the excretion of THp and alpha-1 and beta-2 MG is a useful addition to present
      clinical standards for recognising early changes in renal function. The increases
      in the postoperative period after cardiac surgery showed tubular damage even in
      patients without predictive risk factors or clinical signs. In patients with
      renal dysfunction open heart surgery and extracorporeal circulation led to
      significant tubular damage.

PMID- 7573903
TI  - [Intraoperative calorimetry in aortic bifurcation reconstruction].
AB  - Oxygen uptake (VO2) and carbon dioxide elimination (VCO2) can be measured with an
      indirect calorimeter, this method is well established in routine monitoring of
      ICU patients to evaluate metabolic state as a reflection of stress. In various
      experimental studies it was demonstrated that anaesthetics can influence whole
      body metabolism. The purpose of this study was to examine whether indirect
      calorimetry can be used intraoperatively during routine anaesthesia and whether
      presumable changes in metabolism can be detected immediately. Abdominal aortic
      cross-clamping changes circulation, nutritional supply of the lower extremities
      and thus VO2 and VCO2. We therefore used this operation for our study. METHOD.
      Eleven patients, mean age 64 years, undergoing reconstruction of the aortic
      bifurcation, were studied. After premedication with piritramid and atropine,
      total intravenous anaesthesia (TIVA) was performed with fentanyl and midazolam
      after an induction with thiopental. Patients were ventilated with a Servo
      Ventilator 900 D and a constant FiO2 of 0.5, without N2O. Routine monitoring
      consisted of ECG, pulsoximetry, CVP and continuous AP. VO2 and VCO2 were measured
      with a Deltatrac (Datex), and data were registered every minute. For statistical
      evaluation we used a Wilcoxon-Ranksum test for matched pairs, p < 0.05 was
      considered significant. Data from specific time (5 min after intubation, 5 min
      before clamping; 5, 10 and 15 min after clamping, before declamping and 5 and 10
      min after declamping and at the end of surgery) were calculated. In addition to
      absolute values, we compared the measured VO2 and VCO2 to baseline (5 min before
      clamping = MP2). RESULTS. Mean operating time was 139 min +/- 37; aortic cross
      clamping time for the first extremity was 38 min and 55 min for the second. As
      expected, there was a significant decrease in VO2 (90% of baseline) and VCO2 (75%
      of baseline) during aortic cross-clamping. After declamping VO2 again rose to
      110% of baseline, or to 103% for the second limb. VCO2 increased to only 90% and
      82%, respectively. At the end of surgery VO2 reached baseline, whereas VCO2
      remains at 83%. The respiratory quotient VCO2: VO2 was markedly reduced from 0.95
      +/- 0.156 to 0.73 +/- 0.06 during surgery. The Deltatrac showed every change in
      VO2 without delay; changes in VCO2 seem to occur somewhat retarded. DISCUSSION.
      Aortic cross-clamping leads to a marked decrease in VO2 and VCO2 reflecting the
      temporary reduction in whole-body metabolism. Declamping results in a
      compensatory rise, especially in VO2. VCO2 seems to increase less after
      declamping, perhaps due to the CO2 pool of the organism or to a change in
      metabolism from carbohydrate to mainly fat oxidation. The results of this study
      demonstrate that indirect calorimetry can easily be performed during anaesthesia
      and surgery. Preconditions are a non-rebreathing system without airleak, constant
      FiO2 < 0.6 and no use of nitrous oxide.

PMID- 7573907
TI  - [Water permeability of breathing filters].
AB  - Breathing filters or heat and moisture exchangers (HME), which are placed between
      a tracheal tube and the Y-piece, allow reuse of breathing tubes without changing
      between operations. During low-flow and minimal-flow anaesthesia, condensed water
      accumulates in the breathing circuit. An evaluation of the volume of condensed
      water is given (Fig. 1). It may be possible that water flows onto the filter
      surface, for example, when the breathing tubes are lifted. The water permeability
      of such breathing filters and HME was tested. For the experiments, a commercial
      breathing circuit and ventilator (Drager Sulla 808 + Ventilog) and patient model
      (Fig. 2) were used; 12 breathing filters/HMEs of different manufacturers were
      tested. Only 3 filters were not permeable to the test volume of 20 ml water. The
      authors suggest the water volume be checked routinely and the breathing tubes be
      emptied if necessary.

PMID- 7573905
TI  - [Analgesia-sedation for maxillo-facial surgery with midazolam-pentazocine and
      miazolam-ketamine. Clinical double-blind study of anxiety, analgesia, sedation
      and amnesia].
AB  - Ketamine and midazolam, applied as intravenous medication for conscious sedation
      in day-case maxillo-facial surgery, has been proven to be superior to pentazocine
      and midazolam concerning cardiovascular parameters and respiratory depression.
      The aim of this study was to evaluate the effects of low-dose ketamine/midazolam
      on anxiety, analgesia, amnesia and subjective feelings. METHODS. 140 out-patients
      (ASA I) were randomly divided into four groups. The double-blind study was
      prospective. CONTROL GROUP: Local anaesthesia (LA), articaine 4% plus epinephrine
      1:200,000 (n = 35); test group P/M: LA, additional pentazocine 0.40 mg/kg bw and
      midazolam 0.075 mg/kg bw i.v. (n = 35); test group K25/M: LA, additionally
      ketamine 0.25 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35), test group
      K50/M: LA, additionally ketamine 0.5 mg/kg bw and midazolam 0.075 mg/kg bw i.v.
      (n = 35). LA was injected 3 min after application of the systemic medication in
      the test groups or application of a placebo (saline 0.9%) in the control group.
      Three further minutes later, operation was started. For evaluation
      questionnaires, visual analogue scales (VAS) and the state-trait anxiety
      inventory (STAI) were used. For testing retrograde and anterograde amnesia,
      acoustic sensations were delivered before application of the systemic medication
      (a Christmas carol) and during operation (the German national anthem). RESULTS.
      The control group and the test groups were comparable with regard to biological
      data, duration of operation, applied dosage of local anaesthetics and actual
      anxiety before operation. The patients in all test groups rated intraoperative
      anxiety as mild, in contrast to the control group. Nearly no pain sensation
      during the operation was remembered in all test groups. Retrograde amnesia was
      not found in any group. Complete anterograde amnesia was observed in all test
      groups with respect to the intraoperative sensation, but even in the control
      group 50% of the patients did not remember having heard the national anthem. As
      subjective feelings negative criteria were mainly reported in the control group,
      where as in all test groups positive sensations dominated. Dreams were reported
      mostly after the higher dosage of ketamine, but no patient experienced any
      unpleasant dreams. The clinical assessment of the different regimes were
      excellent for test groups P/M and K50/M, modest for the control group and test
      group K25/M. Postoperatively, patients of test group P/M were remarkably sedated,
      but no clinically relevant sedation or motor weakness were observed in the other
      groups. Postoperative pain sensations were rated more intense in all test groups
      than in the control group. In test groups P/M and K25/M an increasing pain level
      was recorded during the postoperative period, with the consequence of a higher
      demand rate for analgesics. CONCLUSIONS. Dental surgery can be performed safely
      with low-dose ketamine/midazolam. Compared to pentazocine/midazolam, the higher
      dosage of ketamine (0.5 mg/kg bw) showed identical results intraoperatively, but
      was superior during the postoperative period (vigilance), and thus may represent
      a suitable dosage. The lower dosage of ketamine resulted in worse operating
      conditions, but a dosage higher than 0.5 mg/kg bw might lead to unconscious
      sedation and might increase the frequency of unpleasant dreams.

PMID- 7573906
TI  - [Anesthesia with propanidid in a liposomal preparation. An experimental study in
      swine].
AB  - BACKGROUND: Propanidid was widely used as a short-acting i.v. anaesthetic until
      it was withdrawn due to severe haemodynamic side effects. It was presumed that
      anaphylactoid reactions with massive histamine release were caused by the solvent
      cremophor rather than by propanidid itself. A new liposomal preparation of
      propanidid was examined in this animal study and compared with propanidid in
      cremophor solution and with propofol. METHODS: Eighteen pigs were randomly
      assigned to one of the following groups: Group 1 (n = 6): Propanidid in liposomal
      preparation (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 60
      mg/kg, followed by continuous infusion of 400 mg/kg.h. Group 2 (n = 6):
      Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon Richter, Budapest)
      15 mg/kg, 100 mg/kg.h. Group 3 (n = 6): Propofol (Disoprivan, Zeneca, Plankstadt,
      Germany) 5 mg/kg, 20 mg/kg.h. After induction and tracheal intubation, the
      animals were ventilated with 50% oxygen in air. Basic monitoring included
      noninvasive blood pressure measurements, electrocardiographic monitoring, and
      capnography. In a short surgical procedure, arterial and pulmonary artery
      catheters were placed via the right carotid artery and right internal jugular
      vein, respectively. As soon as the animals responded to a pain stimulus a second
      anaesthetic induction was performed, followed by a 60-min continuous infusion of
      the agent studied with invasive haemodynamic monitoring including arterial and
      pulmonary arterial pressures and cardiac output. Blood samples were taken for the
      measurement of serum levels of adrenaline, noradrenaline, cortisol, aldosterone,
      adrenocorticotropic hormone, and histamine. RESULTS: Intubation conditions and
      quality of anaesthesia were best in propofol animals, followed by PropaCrem
      animals. In spite of the large dose of 410 mg/kg.h, resulting in a volume load of
      as much as 16.4 ml/kg.h, the PropaLip animals showed evidence of poor anaesthetic
      quality. In group 1 we recorded the highest increases in heart rate (91 vs.
      115/min), cardiac output (5.4 vs. 7.7 l/min), plasma catecholamine levels, and
      histamine concentrations (124-268 ng/ml). CONCLUSIONS: In our animal study,
      propanidid in liposomal preparation failed to show promise as a new anaesthetic
      agent. Our results are discussed in view of a drug targeting the cells of the
      reticuloendothelial system, especially the liver, where liposomes are eliminated
      from the blood. This may result in the transport of propanidid to one of its
      major places of inactivation.

PMID- 7573909
TI  - [Nitrous oxide exposure to personnel in a recovery room with modern climate
      control].
AB  - Epidemiologic studies have shown that trace concentrations of inhalation
      anaesthetics polluting the air of operating theatres could have deleterious
      effects on the personnel's health. Nitrous oxide (N2O) oxidises vitamin B12 and
      thus decreases DNA production by inactivation of methionine synthase. Therefore,
      the United States and most European health authorities recommend threshold values
      to protect against potential health risks. These values range from 25 to 100 ppm,
      expressed as time-weighted averages (TWA). There is a lack of data concerning
      measurements of trace concentrations under defined conditions. The aim of this
      study was to quantify levels of N2O in a recovery room (RR) with an air
      conditioning system. METHODS. Trace concentrations of N2O were determined in the
      main RR of the University Hospital of Regensburg (Germany). Measurements were
      taken for 5 days from 8:00 a.m. to 8:00 p.m. Trace concentrations of N2O were
      measured directly by means of a highly sensitive photoacoustic infrared
      spectrometry analyser. The lower detection limit was 0.03 ppm. Samples of room
      air were taken continuously from six different places in the recovery room, five
      of which had a distance of 50 cm to the patients' heads. One point represented
      the nurses' desk 5 m away from the patients. TWAs were calculated for each day
      and location. RESULTS. All values were below 5 ppm TWA at each location. Typical
      TWA (range) values recorded at day 2 were for point 1:3.5 ppm (0.4-8.9), point
      2:3.2 (0.5-7.3), point 3:3.0 (0.5-5.4), point 4:3.7 (0.5-21.2), point 5:3.2 (0.6
      6.6), and at the nurses' desk 3.3 (0.5-6.3). Peak concentrations of nearly 25 ppm
      were reached for at least 10 min. Significant differences between the days and
      locations could not be found (P < 0.05, Wilcoxon test). CONCLUSION. Exposure to
      N2O in a climatised RR is determined by several factors: (1) efficacy of air
      conditioning, with 10.7 changes per hour without recirculation; (2) recovery room
      size; (3) transport of the patients takes about 15 min, during which some
      quantities of N2O leave the patient; and (4) high numbers of patients staying 2
      and more hours in the recovery room and exhaling smaller concentrations of N2O
      into the room air. Because of these factors, all measured values are
      significantly below the standard international threshold values. Under other
      conditions of room design, such as ventilation and size, measured values may be
      higher.

PMID- 7573910
TI  - [Gastrointestinal motility disorders in intensive care patients].

PMID- 7573904
TI  - [Flow pattern of respiratory gases in superimposed high-frequency jet ventilation
      (SHFJV) with the jet laryngoscope].
AB  - High-frequency ventilation techniques have been applied for a number of years for
      laryngeal surgery in order to ventilate patients without endotracheal tubes or
      catheters. A further development of high-frequency jet ventilation (HFJV) is the
      technique of superimposed HFJV (SHFJV), which was achieved by combining low- and
      high-frequency jet streams. Although good clinical results were observed, which
      have been published in the past, the clinical details of development of SHFJV
      have not been previously published. METHODS. In order to understand and study the
      mechanism of superimposition of a high-frequency jet stream, extensive
      experiments on a lung simulator at defined measuring points, which represented
      the operating field in microlaryngeal surgery and the trachea, were conducted
      prior to the clinical application of SHFJV. RESULTS. The measurements
      demonstrated that superposition of the two jet streams led to greater velocity
      during inspiration, and therefore produced an increase in tidal volume and
      entrainment of inspiratory gas. This demonstrates that it is possible to apply a
      HFJV technique in patients even with an open system. During expiration, the
      velocity of the low-frequency gas stream is decreased by the opposing flow of the
      high-frequency jet stream, leading to the buildup of positive end-expiratory
      pressure. The pulsations of the high-frequency jet stream induce continuous
      alveolar ventilation. The positioning of the jet nozzles in the jet laryngoscopy
      has the result that the velocities are already decreased at the tip of the
      laryngoscope and decrease further with distance from the nozzles. This prevents
      possible damage to the laryngeal mucosa.

PMID- 7573908
TI  - [Intra-abdominal bleeding after myocardial infarction with cardiopulmonary
      resuscitation and thrombolytic therapy].
AB  - Adverse effects of resuscitation due to closed-chest cardiac massage are common,
      and the incidence is increased when an incorrect technique is used. Nevertheless,
      thrombolytic therapy of a myocardial infarction can become necessary even after
      cardiopulmonary resuscitation (CPR). In these patients, the risk of thrombolytic
      therapy-induced bleeding is immanent. CASE REPORTS. Within 9 months, two male
      patients aged 44 and 52 years were admitted to the intensive care unit after out
      of-hospital CPR for myocardial infarction with cardiac arrest. In both cases,
      thrombolytic therapy was undertaken due to the cardiovascular situation or
      echocardiographic results. Thrombolytic therapy was successful with regard to the
      ECG changes, but a few hours later both patients demonstrated increasing
      cardiovascular instability. After abdominal sonography, intra-abdominal bleeding
      was suspected. Emergency laparotomy became unavoidable, although the coagulation
      profile was severely impaired in both patients (Tables 1 and 2). Anaesthetic
      management was characterised by introduction of central venous and intra-arterial
      catheters, replacement of volume and oxygen carriers using large-bore IV lines,
      restoration of coagulation factors with fresh frozen plasma, and the choice of
      "modified neuroleptanaesthesia" with blood pressure-adjusted, small doses of
      fentanyl, midazolam, and pancuronium. Intraoperatively, a liver injury due to
      closed-chest cardiac massage was found in both cases. The postoperative courses
      were complicated by respiratory problems, which led to prolonged mechanical
      ventilation, but both patients survived without remarkable neurological deficits.
      CONCLUSION. In patients with thrombolytic therapy after CPR and persisting cardio
      vascular instability, a resuscitation injury with consequent haemorrhagic shock
      should be suspected. For diagnosis, chest X-ray films and abdominal and thoracic
      sonography are useful and practicable, even at the bedside. Anaesthetic
      management should focus on adequate monitoring, replacement of volume and oxygen
      carriers, fast restoration of plasma coagulation, and careful, blood pressure
      adjusted maintenance of anaesthesia.

PMID- 7573911
TI  - Esmarch's mask.

PMID- 7573912
TI  - Breathing systems reclassified.
AB  - The purpose of reclassifying breathing systems is to enhance understanding by
      relating structure to function. A previous classification which appears to
      fulfill this objective is updated to include recent developments in a newly named
      group of systems called "displacement afferent reservoir" (DAR) breathing
      systems. A classification table allows for quick comparison and shows that, of
      the non-absorber systems, the DAR group has the best characteristics of fresh gas
      utilization.

PMID- 7573913
TI  - An enclosed efferent afferent reservoir system: the Maxima.
AB  - A single, lightweight, valveless, non-absorber breathing system, which functions
      with near maximal efficiency (hence the name Maxima) in spontaneous and
      controlled ventilation is described. It may be classified as an enclosed efferent
      afferent reservoir (EEAR) breathing system and is characterised by the selective
      elimination of alveolar gas in all modes of ventilation. A functional description
      explains how this is achieved in the system in spontaneous and controlled
      ventilation. The potential for error which arises in combination systems for
      different switch positions with different modes of ventilation is avoided, as it
      is a single universal system. With no moving parts, mechanical reliability is
      guaranteed. The apparatus deadspace is negligible making the system usable even
      in neonates. Finally, the characteristics of the theoretical ideal non-absorber
      circuit are discussed as this illustrates the objective of the circuit design and
      important physical principles surrounding its function.

PMID- 7573914
TI  - Maxima and Bain breathing systems compared in controlled ventilation.
AB  - The Maxima is a new universal breathing system, which, despite its being
      valveless, functions with near maximal efficiency in spontaneous and controlled
      ventilation. It was compared to the Bain system in controlled ventilation by
      adjusting fresh gas flows (VF) to achieve an end-tidal CO2 of 5% in 40 patients
      aged from one to seventy-six years. They received a combined regional and general
      anaesthetic technique. The overall VF requirement of the Maxima system was:
      weight in kg x 35 ml.min-1.kg-1 + 1160 ml.min-1; the Bain system required VF of:
      weight in kg x 42 ml.min-1.kg-1 + 2070 ml.min-1. The mean VF requirement for the
      Bain system was greater by 45%. Of these forty patients, the results from the
      twenty-four adult patients weighing 50 kg or more gave the respective VF
      requirements for the Maxima and Bain systems of 52 and 71 ml.min-1.kg-1. In a
      separate study using twenty-nine patients, the fractional utilization of fresh
      gas (FU) (or VAe/VF where VAe = effective alveolar ventilation) in the Maxima and
      Bain systems was shown to be 0.94 and 0.71 respectively.

PMID- 7573915
TI  - Comparison in spontaneous ventilation of the Maxima with the Humphrey ADE
      breathing system and between four methods for detecting rebreathing.
AB  - An enclosed efferent, afferent reservoir breathing system (Maxima, Life Air Pty
      Ltd), being valveless, was compared to a simple afferent reservoir system
      (Humphrey ADE, A mode), having a valve, by assessing fresh gas flow (VF)
      requirements, with respect to ventilation (VE), that prevents rebreathing in
      volunteers, awake and breathing spontaneously. The results are recorded in terms
      of the quotient VF/VE associated with the onset of rebreathing. At the same time
      four clinical methods for assessing rebreathing were evaluated from the
      perspective of suitability for practical application during anaesthesia. No
      significant difference was found in the VF requirements between the ADE and
      Maxima breathing systems with respective values obtained for the quotient VF/VE
      of 0.80 and 0.77. Our findings showed that the method of sampling carbon dioxide
      (CO2) at the outflow of the efferent limb of the patient connector (eliminated
      CO2 method) in both afferent reservoir systems provided the highest flow rate and
      most reliable indication for detecting potential or actual rebreathing, when
      attempting to minimize VF. It provides no additional deadspace or resistance to
      gas flow, and has the advantage of being the only qualitative method that is
      reliable for the purpose of detecting the onset of rebreathing.

PMID- 7573916
TI  - A comparative evaluation of pressure-triggering and flow-triggering in pressure
      support ventilation (PSV) for neonates using an animal model.
AB  - The triggering system in pressure support ventilation needs to respond rapidly,
      especially in neonates. The aim of this study was to compare the effects of flow
      triggered and pressure-triggered pressure support ventilation on neonatal
      mechanical ventilation using an animal model. Respiratory flow, airway pressure,
      oesophageal pressure, and diaphragmatic electromyogram were measured during
      pressure support ventilation in five anaesthetized rabbits. The animals were
      connected to a VIPBIRD (Bird, U.S.A.) (CPAP mode, pressure support ventilation, 5
      cm H2O and PEEP 0 cm H2O). Flow-triggering sensitivity was set at 0.2l/min,
      0.5l/min, 1.01l/min, or 1.5l/min. Pressure-triggering sensitivity was set at -1.0
      cm H2O. Shorter trigger delay and longer pressure support time were observed in
      flow-triggering. There was also less diaphragmatic activity in flow-triggering as
      evidenced by the amplitude of integrated diaphragmatic electromyogram and
      negative deflection of oesophageal pressure. The findings suggest that flow
      triggering will prove superior to pressure-triggering in pressure support
      ventilation for neonates.

PMID- 7573918
TI  - Low gastric intramucosal pH: incidence and significance in intensive care
      patients.
AB  - Monitoring of gastric intramucosal pH (pHi) is advocated in critical illness to
      detect tissue acidosis due to regional hypoperfusion. However, the number of
      patients who may benefit from such monitoring remains unclear and the
      relationship between low pHi and outcome requires further definition. Sixty
      consecutive patients with Acute Physiology and Chronic Health Evaluation (APACHE
      II) scores < 30 were studied throughout ICU stay to investigate the incidence of
      low pHi (< 7.32 for > or = 1 hour), its relationship to outcome, and temporally
      associated clinical events. pHi was measured 2 to 6 hours post-ICU admission and
      8-hourly thereafter. Forty-four patients (73%) exhibited low pHi. Fourteen
      patients died in ICU with 13 deaths occurring in the low pHi group (P = 0.05).
      Length of ICU stay was greater in the low pHi group (P = 0.02). The development
      of low pHi was temporally associated with maximal sepsis score, weaning from
      assisted ventilation and commencement of enteral feeding.

PMID- 7573917
TI  - Detection of cerebral venous desaturation by continuous jugular bulb oximetry
      following acute neurotrauma.
AB  - A prospective observational study was performed to assess the reliability of
      fibreoptic oximetric catheters and to identify the incidence and causes of
      jugular bulb oxygen desaturation in patients with acute closed head injury. There
      were twenty-five patients (30 +/- 16 years) with GCS < or = 8 in this study.
      Jugular bulb oximetry, mean arterial pressure, intracranial pressure, end-tidal
      CO2 and pulse oximetry were monitored continuously. Catheter calibration against
      a laboratory oximeter was performed post insertion and thereafter eight-hourly.
      Cerebral venous desaturation was defined as a jugular bulb oxygen saturation <
      55% of > 10 minutes duration. There was a poor correlation for the first in vivo
      calibration (r2 = 0.602, P < 0.001, n = 25). Thereafter a close correlation
      between jugular bulb catheter and oximetry values was demonstrated (r2 = 0.868, P
      < 0.001, n = 205). Forty-two episodes of jugular bulb oxygen desaturation of 88
      minutes mean duration (range 10 to 555) were observed. 83% occurred within 48
      hours following injury. Hypocapnia was associated in 45% of episodes;
      hypoperfusion in 22%; raised ICP in 9% and a combination of the above in 24%.
      Validation with a laboratory oximeter is essential prior to continuous jugular
      bulb oximetry. Sustained episodes of cerebral venous desaturation are frequent
      within the first 48 hours following acute head injury. Factors such as hypocapnia
      and cerebral hypoperfusion that primarily reduce cerebral blood flow are
      predominant.

PMID- 7573919
TI  - The use of "quality-adjusted life years" (QALYs) to evaluate treatment in
      intensive care.
AB  - This study examines the feasibility of using Quality-Adjusted Life Years (QALYs)
      to assess patient outcome and the economic justification of treatment in an
      Intensive Care Unit (ICU). 248 patients were followed for three years after
      admission. Survival and quality of life for each patient was evaluated. Outcome
      for each patient was quantified in discounted Quality-Adjusted Life Years
      (dQALYs). The economic justification of treatment was evaluated by comparing the
      total and marginal cost per dQALY for this patient group with the published cost
      per QALY for other medical interventions. 150 patients were alive after three
      years. Quality of life for most longterm survivors was good. Patient outcome
      (QALYs) was greatest for asthma and trauma patients, and least for cardiogenic
      pulmonary oedema. The tentative estimated cost-effectiveness of treatment varied
      from AUD $297 per QALY for asthma to AUD $2323 per QALY for patients with
      pulmonary oedema. This compares favourably with many preventative and non-acute
      medical treatments. Although the methodology is developmental, the measurement of
      patient outcome using QALYs appears to be feasible in a general hospital ICU.

PMID- 7573920
TI  - Anaesthesia for adults with cystic fibrosis.
AB  - Cystic fibrosis is an autosomal recessive disorder which affects one in 2500 live
      births. It is a multisystem disease and has a variety of presentations. The major
      clinical features affect the gastrointestinal and respiratory tracts. Severe
      respiratory disease, diabetes and gastroesophageal reflux are common features of
      concern to anaesthetists. Improved care of young patients has allowed many to
      survive into adulthood. Lung transplantation has significantly improved the
      outlook for many patients. At Alfred Hospital, 74 patients with cystic fibrosis
      underwent 149 procedures from January 1978 to January 1994, with a mortality of
      0.6% (95% CI 0.4%-0.8%). This retrospective cohort study describes the
      anaesthetic management and perioperative care of these patients. Most of the
      anaesthetics were for procedures related to cystic fibrosis but 12% were for
      unrelated conditions. Cystic fibrosis related procedures include diagnostic,
      venous access, enteral feeding procedures, treatment of complications of cystic
      fibrosis and lung transplantation. Despite extremely poor respiratory function,
      these patients can be managed with acceptably low postoperative mortality (1%).
      Pre- and postoperative care must be directed towards optimal clearance of viscous
      respiratory secretions. Procedures need to be planned so that optimal care can be
      given by each member of the team caring for cystic fibrosis patients.

PMID- 7573922
TI  - Excision of bilateral carotid body tumours.

PMID- 7573923
TI  - Overwhelming gram negative septic shock in haemochromatosis.

PMID- 7573924
TI  - Bilateral vocal cord paralysis following endotracheal intubation.

PMID- 7573925
TI  - Contralateral pulmonary oedema.

PMID- 7573926
TI  - Video-assisted thoracoscopy for spontaneous haemopneumothorax.

PMID- 7573921
TI  - EMLA cream prior to insertion of elective epidurals.
AB  - A randomized double-blind study was conducted in 83 women scheduled for elective
      caesarean section to determine the efficacy of EMLA and lignocaine infiltration
      for epidural insertion. The patients were randomly allocated to one of three
      groups: Group A (EM/LIG) received EMLA and intradermal and subdermal 1%
      lignocaine infiltration, Group B (EM/SAL) EMLA and saline while Group C (PL/LIG)
      received placebo cream and 1% lignocaine. Assessments using a 100 mm pain score
      were performed on skin infiltration and after subsequent insertion of a 16 gauge
      Tuohy needle into the supraspinous ligament. Skin changes under the applied cream
      and nursing rating of patients' response were also noted. Statistical analyses
      were performed using Kruskal-Wallis and Fisher's Exact Tests. Groups were
      comparable for age, weight, parity and EMLA application time (interquartile range
      105-150 minutes). There were significantly higher pain scores for skin
      infiltration in Group C (PL/LIG) (P < 0.01) and for epidural needle insertion in
      Group B (EM/SAL) (P < 0.05). We concluded that in this patient population, the
      application of EMLA cream for at least 90 minutes plus 1% lignocaine infiltration
      optimized patient comfort for epidural insertion.

PMID- 7573927
TI  - Stroke caused by inadvertent intra-arterial parenteral nutrition.

PMID- 7573928
TI  - Toxic shock syndrome in a male secondary to myositis of the arm.

PMID- 7573929
TI  - Cerebral lupus presenting a sepsis syndrome.

PMID- 7573931
TI  - Failed nasogastric intubation in undiagnosed carcinoma of the oesophagus.

PMID- 7573930
TI  - Upper airway obstruction in Parkinson's disease.

PMID- 7573934
TI  - ANZICS/CACCN annual scientific meeting on intensive care. Sydney, New South
      Wales, October 1994. Abstracts.

PMID- 7573933
TI  - The Geoffrey Kaye Oration. ASA AGM, Nadi, Fiji, October 10, 1994.

PMID- 7573932
TI  - Spinal subdural haematoma following combined spinal-epidural anaesthesia.

PMID- 7573935
TI  - Intraoperative nasotracheal to orotracheal tube change in a patient with Klippel
      Feil syndrome.

PMID- 7573936
TI  - Alterations in endotracheal tube position with head and neck movement.

PMID- 7573937
TI  - Tunnelled epidural catheters.

PMID- 7573938
TI  - Tunnelled epidural catheters.

PMID- 7573939
TI  - Naproxen premedication for laparoscopic sterilization.

PMID- 7573940
TI  - Displacement of double-lumen tubes.

PMID- 7573941
TI  - Percutaneous axillary artery insertion of an intra-aortic balloon pump.

PMID- 7573942
TI  - High humidity affects HemoCue microcuvette function.

PMID- 7573944
TI  - Gravity feed and epidural infusions.

PMID- 7573943
TI  - Difficulty in using the Schroeder oral/nasal directional stylet.

PMID- 7573946
TI  - An assay method for nitric oxide synthase in crude samples by determining product
      NADP.
AB  - An assay method for nitric oxide synthase (NOS) was developed based on
      fluorometric or enzymatic determination of NADP+. An aliquot (< or = 2
      microliters) of crude enzyme sample, homogenate or supernatant of rat cerebellum,
      was added to a reaction mixture containing arginine, NADPH, and O2 and incubated
      at 25 degrees C for 30 min. A strongly fluorescent substance was formed from a
      product, NADP+, and measured (fluorometric assay). When rat cerebellar layers
      were assayed, freeze-dried sections of layers (0.2 to 2 micrograms dry wt) were
      added directly into 1.24 microliters of NOS reaction mixture and the total NADP+
      formed in picomole amounts was specifically amplified up to 4000-fold and
      determined, using an enzymatic NADP cycling amplification reaction (enzymatic
      cycling assay). NOS activity was calculated as the difference in NADP+-forming
      activity in the absence and presence in the reaction mixture of NG-nitro-L
      arginine, a specific inhibitor of NOS. Enzymatic activity was analyzed in rat
      cerebellar supernatants by two procedures. With supernatants (and purified
      macrophage NOS), the ratio between the specific activities on a protein basis
      using the present NADP+ formation assay and using [3H]citrulline formation from
      [3H]arginine as substrate was 2. The distribution of NOS activity was shown
      between the particulate and supernatant fractions of rat cerebellum. The
      molecular and granular layers of rat cerebellum contained similar NOS activities,
      while the activity in the white matter was negligibly low. NOS distribution is
      also reported among rat organs.

PMID- 7573945
TI  - Revolutions in rapid amplification of cDNA ends: new strategies for polymerase
      chain reaction cloning of full-length cDNA ends.
AB  - Rapid amplification of cDNA ends (RACE) is a polymerase chain reaction (PCR)
      based technique which was developed to facilitate the cloning of full-length cDNA
      5'- and 3'-ends after a partial cDNA sequence has been obtained by other methods.
      While RACE can yield complete sequences of cDNA ends in only a few days, the RACE
      procedure frequently results in the exclusive amplification of truncated cDNA
      ends, undermining efforts to generate full-length clones. Many investigators have
      suggested modifications to the RACE protocol to improve the effectiveness of the
      technique. Based on first-hand experience with RACE, a critical review of
      numerous published variations of the key steps in the RACE method is presented.
      Also included is a detailed, effective protocol based on RNA ligase-mediated
      RACE/reverse ligation-mediated PCR, as well as a demonstration of its utility.

PMID- 7573947
TI  - Automated analysis of cellular metabolites at nanomolar to micromolar
      concentrations using bioluminescent methods.
AB  - Automated bioluminescent assays for lactate, oxoglutarate, pyruvate, ammonia,
      NAD, glutamate, ATP, phosphocreatine, creatine, and NADH were developed from
      existing spectrophotometric and fluorometric assays. A key feature was the
      development of a luminescent reagent that was not only relatively cheap and
      stable, but also could be stored frozen. With this reagent it was possible to
      measure NADH concentrations as low as 0.1 nM in a 25-microliters sample. The
      sensitivity of the other assays was limited by contamination of the enzymes and
      cofactors used in the assays and ranged from 0.05 to 25 microM with sample
      volumes of 0.75 - 10 microliters.

PMID- 7573948
TI  - Mass-spectrometric analysis of N-acetylchitooligosaccharides prepared through
      enzymatic hydrolysis of chitosan.
AB  - A semipreparative scale chromatography of N-acetylchitooligosaccharides (GlcNac)2
      7 on a reversed-phase C-16 HPLC column is reported. The initial material was
      obtained by enzymatic hydrolysis of chitosan with a complex of chitinases from
      Streptomyces kurssanovii, followed by a complete acetylation of amino groups.
      Isolated N-acetylchitooligosaccharides were characterized by the mass
      spectrometric method. On interacting with the sample, the fragments of 252Cf
      caused desorption of quasi-molecular ions of the substance. All mass spectra of
      chitin oligomers contained intense quasi-molecular ions [M + Na]+ and a less
      intense [M + K]+ ion. Fragment ions, compared to the quasi-molecular ion [M +
      K]+, had a lower intensity and confirmed the structure of samples under study.
      Due to this phenomenon, an accurate analysis of both individual compounds and
      mixtures of N-acetylchitooligosaccharides (n = 2-7) may be performed.

PMID- 7573949
TI  - Identification and quantitation of choline glycerophospholipids that contain
      aldehyde residues by fluorometric high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was established for the
      fractionation of oxidized choline glycerophospholipids (CGPs) that contain
      aldehyde residues, after their derivatization with a fluorescent reagent 4-(N,N
      dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole (DBD-H). DBD-H
      efficiently reacted with the aldehyde residues of phospholipids at room
      temperature. Fluorescent derivatives of aldehydic phospholipids were well
      separated into species that contained aldehyde groups at different sites. The
      relationship between the amount of each derivative and the signal was linear over
      a wide range and amounts as low as several picomoles of aldehydic CGP could be
      detected. This method is applicable to the quantitation of aldehydic
      phospholipids in peroxidized membranes of red blood cells. In the present study,
      formation of aldehydic choline glycerophospholipids was demonstrated for the
      first time in peroxidized red blood cell membranes and the compounds were
      quantitated.

PMID- 7573951
TI  - Quantitative pH imaging in cells using confocal fluorescence lifetime imaging
      microscopy.
AB  - The pH-sensitive probe carboxy SNAFL-1 can be used for imaging using ratiometric
      and fluorescence lifetime techniques. The former method suffers from the drawback
      that quantitative pH imaging in cells requires a time-consuming and cumbersome
      calibration procedure. In contrast, straightforward calibrations in buffer
      suffice for fluorescence lifetime imaging. This is illustrated here by a
      comparative study of the two techniques under different controlled conditions.
      The effect of probe concentration, protein concentration, and hydrophobicity, the
      contents of damaged cells and living cells on the emission ratio, and the
      fluorescence lifetime of carboxy SNAFL-1 were studied. The results clearly
      demonstrate that the fluorescence lifetime imaging technique is more convenient
      than the ratiometric method for pH determination.

PMID- 7573950
TI  - Characterization of endonucleolytic activity of HIV-1 integrase using a
      fluorogenic substrate.
AB  - Retroviruses require viral DNA to be synthesized by reverse transcription in the
      cytoplasm followed by integration of the resulting viral DNA into the host
      chromosome in the nucleus. Reverse transcription and integration, essential steps
      in the life cycle of retroviruses, are possible targets in the development of
      antiviral reagents. One attractive target is the integrase protein, a product of
      the retroviral pol gene which is solely responsible for the retroviral
      integration process through cutting and joining reactions. When screening for
      massive numbers of antiviral agents, a rapid and precise assay is ideal. We
      report the application of fluorescence resonance energy transfer (FRET) with
      fluorescein and eosin as the energy transfer pair to characterize HIV-IN-mediated
      DNA cleavage reactions. Past concerns with applications of FRET to DNA were due
      to interactions of the fluorophore with the DNA, resulting in quenched
      fluorescence. However, in this study these concerns have been resolved with the
      use of a nucleotide analog with a 12-carbon linker arm, 5-amino (12)-2'
      deoxyuridine beta-cyanoethyl phosphoramidite. Steady-state fluorescence studies
      show that cleavage of the fluorogenic substrate by integrase results in
      enhancement of quenched donor fluorescence intensity. The fluorescence assay was
      confirmed by autoradiographic analysis of the cleavage reaction with radiolabeled
      fluorogenic substrate. This fluorescence assay will facilitate both detailed
      kinetic studies and the rapid screening of novel integrase inhibitors.

PMID- 7573953
TI  - Two-dimensional electrophoresis southern transfer method for detecting human
      genome variability using a LINE-1 sequence probe.
AB  - A "high-resolution, two-dimensional Southern transfer" method has been developed
      and was used to examine the distribution of a class of interspersed repeated
      sequences in human genomes. This method consists of two separate restriction
      enzyme digestions, including an in situ digestion, and two-dimensional
      electrophoresis using a large-sized agarose gel. The first 163-base-pair region
      of the human LINE-1 full-length sequence was used to probe human genomic DNA from
      placental tissue samples. About 900 LINE-1 signals were resolved from each DNA
      sample within a 2-D plane. The bulk of the fragments were between 0.5 to 23
      kilobases in length. At a minimum 15 variant signals were detected between DNA
      samples from male and female individuals and at a minimum 16 variant signals were
      detected between two different female samples. This approach can potentially be
      used to perform high-resolution human genome fingerprinting analyses.

PMID- 7573952
TI  - A lifetime-based optical CO2 gas sensor with blue or red excitation and stokes or
      anti-stokes detection.
AB  - We describe the fabrication and characterization of an optical CO2 sensor based
      on the change in fluorescence lifetimes due to fluorescence resonance energy
      transfer from a pH-insensitive donor, sulforhodamine 101, to a pH-sensitive
      acceptor, either m-cresol purple or thymol blue, entrapped in an ethyl cellulose
      film. A phase transfer agent allows incorporation of the dyes and water into the
      film, while providing an initially basic environment for the acceptor. Diffusion
      of CO2 into the water entrapped in the film produced carbonic acid, causing a pH
      dependent decrease in the spectral overlap of the acceptor absorbance with the
      donor emission, and decreased energy transfer, resulting in increased SR101 donor
      lifetimes. The lifetime changes were detected as a change in the phase of the
      emission, relative to the modulated excitation, and were insensitive to
      excitation intensities and emission signal levels. In addition to an externally
      modulated 442-nm light source, we excited the sensor with a directly modulated
      635-nm laser diode and detected the anti-Stokes emission. The CO2 sensor is not
      fragile and can provide stable readings for weeks. The use of fluorescence
      resonance energy transfer, along with the simple entrainment procedure, allows
      facile change of the CO2 response range through change of the acceptor dye and
      the use of laser diode excitation sources.

PMID- 7573955
TI  - Degradation kinetics of antagonist [Arg6, D-Trp7,9, MePhe8]-substance P [6-11] in
      aqueous solutions.
AB  - Antagonist [Arg6, D-Trp7,9, MePhe8]-substance P {6-11} was subjected to a
      systematic stability study in which kinetic parameters were obtained for the
      degradation of this hexapeptide under several well-defined conditions. The
      influences of pH, temperature, ionic strength, buffer concentration, and initial
      concentration of the peptide on the reaction rate constant, kobs, were
      investigated with a stability-indicating reversed-phase high-performance liquid
      chromatographic system. From the pH-log kobs degradation profile, obtained at 63
      degrees C, it appears that antagonist [Arg6, D-Trp7,9, MePhe8]-substance P {6-11}
      shows its maximum stability around pH 4.2. The half-life at this pH and
      temperature is 150 days. In both the hydroxyl- and proton-catalyzed parts of the
      pH-log kobs degradation profile, the influence of temperature was investigated
      and Arrhenius plots were constructed. The activation energies in both parts were
      comparable; however, the frequency factor in the hydroxyl-catalyzed part was 3.3
      x 10(4) times higher than in the proton-catalyzed part. Eyring analysis of the
      data reveals that in both acidic and alkaline media the overall degradation was
      endotherm (delta H++ as well as delta G++ positive between 273 and 373 degrees K)
      and the entropy was negative. Increasing ionic strengths in acidic media causes
      an increase in kobs, while in alkaline media the kobs decreases with increasing
      ionic strength. Increasing buffer concentrations of acetate, phosphate, and
      carbonate led to an increase of kobs values. Drug concentrations up to 1 mg/ml at
      pH 10.8 and constant temperature and ionic strength have no influence on the
      overall degradation rate. At higher concentrations, above 1 mg/ml, kobs
      decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7573957
TI  - Effects of solutes on optical properties of biological materials: models, cells,
      and tissues.
AB  - Perturbations of scattering background for absorbance measurements by photon
      diffusion techniques complicate algorithms used for determining the concentration
      of blood and the saturation of hemoglobin in tissues. In order to better define
      these perturbations, we have undertaken a study of the effect of solutes, some of
      physiological importance, upon the scattering of three types of model systems: a
      lipid vessel suspension (Intralipid), a cell suspension (Baker's yeast), and a
      tissue (perfused liver). A simple formula relates absorbancy change to
      proportional changes of the input/output separation rho and the square root of mu
      a and mu's in relation to a relevant model system. Thus, absorbance changes at
      850 nm slopes and intercepts are measured as a function of rho; the absorption
      and reduced scattering coefficient, mu a and mu's, are calculated. We studied
      each of these cases as a function of the perturbation induced by low-molecular
      weight polyhydroxy solutes, generally sugars (mannitol, fructose, sucrose, and
      glucose), alcohols (propanediol and methanol), and electrolytes (sodium and
      potassium chloride). Dilatometric studies indicate volume changes of the solvent
      system and afford correction factors. The slopes are approximately +/- 0.5 x 10(
      4) OD/mM solute per centimeter separation of input/output per percent scatter
      (yeast or Intralipid) and indicate possible physiological detection of solutes in
      tissues in the millimolar range. The large optical effects of temperature upon
      the solute effect on model systems and of osmotic and perfusion pressures on the
      perfused liver further complicate the possibility of quantitative in vivo studies
      of these solutes.

PMID- 7573954
TI  - A continuous spectrophotometric assay for simultaneous measurement of calcium
      uptake and ATP hydrolysis in sarcoplasmic reticulum.
AB  - A continuous, spectrophotometric assay to simultaneously measure Ca uptake and
      ATP hydrolysis has been developed, in order to assess the function of the Ca
      ATPase in skeletal and cardiac sarcoplasmic reticulum (SR) vesicles. The
      absorbance of Fura Red was measured continuously at 490 nm, in EGTA-buffered
      solutions containing initial free ionized calcium concentrations of 300 nM, 500
      nM, 790 nM, and 2 microM, during assays of oxalate-facilitated or phosphate
      facilitated active calcium uptake in skeletal SR. Simultaneous measurement of ATP
      hydrolysis during the measurement of phosphate-facilitated Ca uptake was
      accomplished by measuring the disappearance of NADH at 340 nm, coupled to the
      hydrolysis of ATP by an enzyme-linked, continuous ATPase assay. This new method,
      unlike the standard 45Ca-filtration assay, measures calcium uptake in real time
      and eliminates the need for radioactivity. Moreover, the rates of calcium uptake
      and ATP hydrolysis are measured simultaneously, allowing the direct quantitative
      comparison of the two parameters. This assay will facilitate the characterization
      of Ca-ATPase function and malfunction in skeletal and cardiac SR and advances the
      methodology for comparison of normal and physically, chemically, or biologically
      altered Ca-ATPase.

PMID- 7573958
TI  - Preparative synthesis of beta-L-malyl-coenzyme A assisted by malyl-coenzyme A
      synthetase from Pseudomonas AM1.
AB  - beta-L-Malyl-CoA was synthesized from L-malate, CoA, and ATP in the presence of
      catalytic amounts of L-malyl-CoA synthetase (thiokinase) from Pseudomona AM1,
      which had been 50-fold purified by protamine sulfate precipitation, ammonium
      sulfate precipitation, chromatography on DEAE-cellulose, and affinity
      chromatography on High Trap Blue in less than 2 days. The homogeneous enzyme was
      free of L-malyl-CoA lyase and showed 63% homology with succinyl-CoA synthetase
      from Thermus aquaticus in its N-terminal sequences. Yields of beta-L-[14C]malyl
      CoA(1-10 mumol) were 70% before and 65% after purification in 0.1-0.5 mumol
      portions by high-performance liquid chromatography on a MN Nucleosil 100-7 C8
      column. For most biochemical work, the product was partially purified with an
      overall 45% yield by chromatography on DEAE-Sephacel. The identity of the
      compound as beta-L-malyl-CoA was verified by chemical and enzymatic tests, and
      also in comparison with its chemically synthesized counterpart. The enzymatic
      synthesis, especially of radioactively labeled beta-L-malyl-CoA, is considerably
      faster, higher in yield, and less problematic than chemical synthesis.

PMID- 7573956
TI  - A general, wide-rage spectrofluorometric method for measuring the site-specific
      affinities of drugs toward human serum albumin.
AB  - Binding of drugs to serum albumin is one of the most important pharmacokinetic
      determinants and the design of drugs should take advantage of this property. In
      the present work, the fluorescent ligands Warfarin and dansylsulfonamide were
      used as probes of IIA site of human albumin and dansylsarcosine as the probe of
      the IIIA site. From the changes in fluorescence upon binding at 37 degrees C, pH
      7.4, the following dissociation constants were determined: Warfarin, 3.43 +/-
      0.69 microM; dansylsulfonamide, 7.57 +/- 0.88 microM; and dansylsarcosine, 6.06
      +/- 1.09 microM. Nonfluorescent ligands displace these probes competitively and
      the type of probe displaced identifies the site specificity of the ligands.
      Nonlinear least-squares analysis of the decrease in fluorescence accompanying the
      displacement yields the stoichiometry and the dissociation constant may also be
      estimated rapidly from displacement at a single competitor concentration. The
      method yields reliable Kd values for at least the range of 0.2 to 100 microM.
      Representative dissociation constants for the IIA site-specific ligands are as
      follows: phenylbutazone, 1.9 +/- 0.3 microM; U-99,499, 1.8 +/- 0.2 microM; U
      96,988, 5.3 +/- 1.5 microM; and U-105,665, 42 +/- 7 microM. For the IIIA site we
      find the following Kd values: oxazepam, 27.7 +/- 2.1 microM; diazepam, 7.7 +/-
      1.0 microM; and ibuprofen, 2.7 +/- 1.2 microM. The method is eminently suitable
      for large-scale screening.

PMID- 7573959
TI  - Monitoring biosynthetic transformations of N-acetyllactosamine using
      fluorescently labeled oligosaccharides and capillary electrophoretic separation.
AB  - Capillary electrophoresis with laser-induced fluorescence detection was used to
      monitor biosynthetic transformations of a labeled derivative of N-acetyllac
      tosamine (beta Gal (1 --> 4) beta GlcNAc, LacNAc) in crude microsomal extracts.
      For this purpose, six authentic standards including LacNAc-O-TMR itself (-TMR, a
      linker arm attached to tetramethylrhodamine), the tri-and tetrasaccharides that
      would form by either alpha (1 --> 2) or alpha (1 --> 3) fucosylation of LacNAc or
      both (i.e., H-type 2, LeX and LeY sequences) were chemically synthesized. The
      potential degradation products produced by galactosidase and hexosaminidase were
      also prepared. All of the standards were kinetically competent substrates for the
      enzymes present in HT-29 cells and could be baseline separated in a single run
      requiring 11 min. The action of competing enzymes acting on the common LacNAc
      sequence could thus be monitored in a single run with sensitivity routinely as
      low as a few thousand molecules.

PMID- 7573960
TI  - Monosaccharide composition analysis of oligosaccharides and glycoproteins by high
      performance liquid chromatography.
AB  - A simple and sensitive high-performance liquid chromatography (HPLC)-based method
      for complete monosaccharide composition analysis of oligosaccharides and
      glycoproteins is described. In this method, an oligosaccharide or glycoprotein is
      first hydrolyzed using an optimized method to give the constituent
      monosaccharides, which are subsequently labeled with 1-phenyl-3-methyl-5
      pyrazolone (PMP) as previously described by Honda et al. (Anal, Biochem. 180, 351
      357, (1989)). The labeled monosaccharides are separated by reverse-phase HPLC
      using a column developed especially for this purpose, monitored by uv absorbance
      at 245 nm, and quantitated by their integration values relative to standards.
      Sialic acids are acid-labile keto-sugars. They are, therefore, released with
      neuraminidases or by mild acid hydrolysis and then converted with neuraminic acid
      aldolase to their corresponding mannosamine derivatives, which are then PMP
      labeled, separated, and quantitated as described above. Individual sialic acids
      including N-acetyl and N-glycolyl neuraminic acids are well resolved and
      quantitated by this method. This method has proven to be highly sensitive,
      requiring only 1 pmol for reliable detection. Quantitative analysis of neutral
      and amino sugars from both oligosaccharide and glycoprotein samples can be
      achieved using one acid hydrolysis and a set of equal molar monosaccharide
      standards. Similarly, quantitation of sialic acids works equally well with both
      free oligosaccharide and glycoprotein samples. Monosaccharide compositions of
      oligosaccharides and glycoproteins determined by this method were found to be
      highly accurate.

PMID- 7573961
TI  - Pressure corrections for CoCl2 as a thermometer in an analytic ultracentrifuge.

PMID- 7573963
TI  - Modified procedure for nonspecific protein staining on nitrocellulose paper using
      Coomassie brilliant blue R-250.

PMID- 7573962
TI  - Several polymers enhance the sensitivity of the southwestern assay.

PMID- 7573964
TI  - Cation-exchange resins release amino acids: consequences for tracer studies.

PMID- 7573965
TI  - Use of rhodamine B isothiocyanate to detect proteoglycan core proteins in
      polyacrylamide gels.

PMID- 7573966
TI  - Identification of dimeric structure of proteins by use of the glutathione S
      transferase-fusion expression system.

PMID- 7573967
TI  - Effects of cooling temperature on the separation of phosphoamino acids.

PMID- 7573968
TI  - Western blot analysis of epidermal growth factor using gelatin-coated
      polyvinylidene difluoride membranes.

PMID- 7573969
TI  - Modified assay for the measurement of biotin in the presence of heparin.

PMID- 7573970
TI  - Determination of the linkage positions of reducing-end residues of
      oligosaccharides by partial periodate oxidation of pyridylaminated derivatives.

PMID- 7573971
TI  - Detection of irradiated chicken meat by analysis of lipid extracts for 2
      substituted cyclobutanones using an enzyme linked immunosorbent assay.
AB  - The means to detect the irradiation of food has been investigated for many years.
      In recent times radiolytic products, termed 2-alkylcyclobutanones (2-CBs), have
      been identified as excellent markers of irradiation in lipid-containing foods. An
      ELISA test was developed, which was capable of detecting a number of these
      compounds in irradiated chicken meat. A polyclonal antiserum was raised to a 2-CB
      containing a terminal carboxyl group conjugated to a carrier protein. This
      antiserum was highly specific for cyclobutanones containing C10 and C12 side
      chains. During assay validation the limit of detection of the assay was
      calculated to be 0.064 microgram of 2-CB per gram of fat, within- and between
      assay variations ranged from 6.7 to 18%. During experimental studies, chicken
      meat irradiated at doses ranging from 2.5 to 10 kGy were assayed and correctly
      identified as being treated. Quantitative comparisons between the ELISA and GC-MS
      revealed a good correlation (r2 = 0.93) between the two methodologies in
      concentrations of 2-CB detected in irradiated samples.

PMID- 7573973
TI  - Quantitative determination of functional thiol groups on intact cell surfaces by
      resonance Raman spectroscopy.
AB  - The sensitivity and selectivity of resonance Raman spectroscopy, combined with
      electronic spectroscopy, has been used to develop a method to quantify the
      membrane thiol population in situ in viable erythrocytes. This technique is based
      on the thiol-disulfide reaction of Ellman's reagent (5,5'-dithio-bis-2
      nitrobenzoic acid). It has the advantage that continuous monitoring of lysis is
      simple and a correction can be made for any interference resulting from lysis. In
      addition, the extent of reaction can be expressed as a ratio of the reagent
      signal, providing an internal calibrant.

PMID- 7573972
TI  - Determination of furazolidone in porcine tissue using thermospray liquid
      chromatography-mass spectrometry and a study of the pharmacokinetics and
      stability of its residues.
AB  - A method is presented for the detection of the nitrofuran, furazolidone, in
      porcine tissue. Following methanol-buffer extraction of the tissue, liquid
      partitioning, and solid-phase clean-up, samples are analysed by using thermospray
      LC-MS monitoring the positive ion m/z 243 with filament-assisted ionization. The
      LOD is 1 microgram kg-1. The assay is used to investigate the depletion of
      furazolidone from tissue and sample stability post mortem. It is necessary to
      snap-freeze samples by immersion in liquid nitrogen immediately upon collection
      in order to improve the stability of residues in tissue.

PMID- 7573974
TI  - Determination of arsenic, cadmium and lead in porcine and bovine kidneys by
      electrothermal atomic absorption spectrometry.
AB  - This paper describes an ETAAS method to quantify residues of arsenic, cadmium and
      lead in porcine and bovine kidneys. The results of a survey conducted during 1993
      are tabulated. Analysis was performed by ETAAS with a stabilized-temperature
      platform furnace. The determinations were performed in the linear ranges 0.5-150,
      0.04-2.0 and 1.1-75 micrograms l-1 for As, Cd and Pb, respectively, in the acid
      digests which were obtained under controlled conditions of temperature in a
      tetrafluoroethylene apparatus after appropriate dilution and addition of a
      suitable chemical modifier. Extensive quality assurance of the methods was
      performed by the standard additions method and by comparison with a certified
      reference material. The precision was better than 9.9, 8.5 and 9.2% for As, Cd
      and Pb, respectively. Low relative standard deviations of 7.4, 7.0, and 2.8% for
      As, Cd and Pb, respectively, were obtained by comparing the levels found in the
      kidney reference material and the certified values, showing this method to be
      satisfactory and suitable for routine analysis. The mean levels of As, Cd and Pb
      in porcine kidney were 2.11 (1.11-5.49), 0.81 (0.02-4.22) and 0.18 (0.02-0.42)
      microgram g-1 respectively. Those in the adult bovine kidney were 1.77 (0.42
      3.42), 1.26 (0.01-6.16) and 0.73 (0.19-2.55) microgram g-1, respectively, and in
      the young bovine kidney they were 1.33 (0.61-2.56), 0.49 (0.15-1.82) and 0.20
      (0.12-0.29) microgram g-1.

PMID- 7573975
TI  - Analytical validation of a general protocol for the preparation of dose
      controlled solutions in aluminum toxicology.

PMID- 7573976
TI  - Trans-Golgi network (TGN) of different cell types: three-dimensional structural
      characteristics and variability.
AB  - BACKGROUND: The trans-Golgi network (TGN) is generally considered as a distinct
      and permanent structural compartment of the Golgi apparatus of various cell
      types. To verify this postulate we examined and compared the three-dimensional
      characteristics of the TGNs of 14 different mammalian cell types as presented in
      our various publications since 1979 when we initially described the trans-tubular
      network of Sertoli cells. METHODS: In all these studies we used low and high
      voltage electron microscopes on thin or thick sections of tissues fixed with
      glutaraldehyde and postfixed with reduced osmium. The sections were stained with
      uranyl acetate and lead citrate. Stereopairs, prepared from photographs of tilted
      specimens, permitted a direct observation of the three-dimensional structure of
      the various elements of the Golgi apparatus. RESULTS: The TGNs are multilayered
      and extensive in cells which do not form large typical secretory granules
      (Sertoli cells, nonciliated cells of ductuli efferentes, spinal ganglion cells)
      but have an extensive lysosomal system. The TGN is absent in cells forming very
      large secretory granules (secretory cells of seminal vesicles and lactating
      mammary glands). The TGNs are small in cells producing small to medium-size
      secretory granules and/or appear as residual fragments on the trans aspect of the
      Golgi stacks (e.g., mucous cells of Brunner's gland, pancreatic acinar cells,
      etc.). In cells with multiple and extensive TGNs, a continuity of these tubular
      networks with the two or three transmost saccules of the stack is observed but
      there are seemingly no connections between the TGNs. Whenever the TGNs are
      present, they do not form a continuous structure along the Golgi ribbon. However,
      they do present, in all cases, configurations suggestive of desquamation and
      renewal. CONCLUSIONS: The structure of the TGN varies considerably from one cell
      type to another, being extensive in cells not showing typical secretory granules
      but having an extensive lysosomal system, while in secretory cells showing small
      or large secretory granules the TGN is either small or even entirely absent.

PMID- 7573979
TI  - Alveolar bone turnover in male rats: site- and age-specific changes.
AB  - BACKGROUND: This study compares alveolar bone turnover adjacent to distally
      drifting maxillary first molar teeth of rapidly and slowly growing rats. METHODS:
      Two groups of forty male rats (1 and 3 months) were sacrificed. Sera were
      analyzed for acid (AcP), alkaline (AlkP), and tartrate-resistant acid phosphatase
      (TRAP). Bone histomophometry was done on parasagittal sections of maxillary
      molars. Molar drift was quantified cephalometrically. RESULTS: Distal surface
      contained more osteoclasts and higher osteoclast percents than mesials at both
      ages (P < 0.001). There were also more osteoclasts on the distals of the older
      rats as compared to the young (P < 0.001). Osteoblast percents were higher (P <
      0.001) in the older rats on both surfaces. Mesials had higher double-labeled
      surface, MAR and BFR than distals in the younger rats (P < 0.001). The younger
      rats had higher (P < 0.001) AlkP, AcP, and TRAP. There were no age-specific
      differences in rate of molar drift. A model of rate of molar drift (P < 0.0015)
      containing bone formation measures accounts for 54.9% of the variability.
      CONCLUSIONS: We conclude that the bone turnover dynamics adjacent to maxillary
      first molars represent predominantly remodeling on the distal in both groups and
      modeling on the mesial only in the young rats, that distal molar tooth drift
      reflects alveolar bone turnover, and that alveolar bone manifests the marked
      reduction in bone cell activity that occurs in the rat skeleton after 8 weeks but
      that this reduction is compensated by recruitment or maintenance of more bone
      cells at these sites.

PMID- 7573978
TI  - Relationships between endothelial cells, pericytes, and osteoblasts during bone
      formation in the sheep femur following implantation of tricalciumphosphate
      ceramic.
AB  - BACKGROUND: The origin of osteoblasts is still controversial. Whereas several
      authors consider the stromal fibroblast of the bone marrow as the osteoprogenitor
      cell, others propose that the osteoblasts can be derived from the "capillary
      system." The present study examines the replacement of tricalciumphosphate (TCP)
      ceramic implanted into an artificial bone defect by newly formed bone. The
      results support the hypothesis that osteogenic cells can be derived from invading
      blood vessels. METHODS: The spongiosa of the trochanter major of sheep was
      removed and the defect was filled with TCP-ceramic. Two months after surgery the
      ceramic implants together with the surrounding bone were removed and processed
      for transmission electron microscopy. Serial ultrathin sections of three newly
      formed osteons were examined. RESULTS: The osteons contain one or two small
      sprouting capillaries, a peripheral layer of osteoblasts, and in between, a
      network of glycogen-rich cells. Some of the glycogen-rich cells are completely or
      partly surrounded by the endothelial basal lamina and are thereby characterized
      as pericytes. Weibel-Palade bodies, which are considered to be a marker of
      endothelial cells, were occasionally observed in glycogen-rich pericytes.
      CONCLUSIONS: Since pericytes differentiate into osteoblasts under in vivo and in
      vitro conditions, and have thus been regarded as osteoprogenitor cells, the
      presence of Weibel-Palade bodies in these cells suggest that osteogenic cells can
      be derived from endothelial cells.

PMID- 7573980
TI  - Satellite cell activation after muscle damage in young and adult rats.
AB  - BACKGROUND: Level exercise leads to focal structural damage in muscle fibers and
      to an increase of creatine kinase in the blood. We questioned whether it also
      induces activation of young and adult muscle satellite cells toward
      proliferation. METHODS: Rats of two different ages, 6 and 16 weeks, were forced
      to run on a level treadmill and killed at different time intervals. The temporal
      profile, up to 3 weeks, of muscle damage was investigated by quantification of
      the focally disturbed fiber area in longitudinal sections of the m. soleus.
      Bromodeoxyuridine (BrdU) was injected before death to determine the labeling
      index of satellite cells. Labeled and unlabeled satellite cells, myonuclei, and
      fibers were counted in cross sections of the belly part of the muscles. RESULTS:
      The muscle fiber damage differed in both amount and temporal profile between
      young and older animals. Damage was already visible immediately after running.
      However, whereas in the younger animal the amount of damage increased gradually
      in time until 8% at 48 hours and disappeared to almost control levels at 1 week
      after running, in the older animals the amount of damage was lower but remained
      present for at least 2 weeks. The cell kinetic data on both groups showed a
      proliferation response of satellite cells throughout the muscle. The effects were
      most pronounced in the older rats. In these rats a large increase of the labeling
      index was found between 24 hours and 1 week, whereas the total number of
      satellite cells was consistently higher from 2 days on until 2 weeks after
      running. In the younger animals roughly the same time pattern was observed.
      CONCLUSION: Since the damage differed in amount and time between the two age
      groups, we conclude that the quick and huge proliferation response is due to
      leakage of mitogenic factors through small membrane disruptions that are
      generated during the exercise itself.

PMID- 7573981
TI  - Ultrastructural and functional differentiation of hepatocytes under long-term
      culture conditions.
AB  - BACKGROUND: Studies on hepatocytes grown in different culture systems have shown
      that these cells rapidly dedifferentiate on a single support with liquid medium
      on top (single gel technique). However, in systems sandwiching them between two
      layers of extracellular matrix (double gel technique), the cells are able to
      regain and maintain typical light microscopical appearance and function. Their
      ultrastructural morphology is as yet unknown. METHODS: Isolated, adult rat
      hepatocytes were grown in both systems, and their fine structure (thin section
      electron microscopy) and the functional ability of albumin production
      (immunoassay) were studied and compared in both culture systems after 2, 7, and
      14 days. RESULTS: The hepatocytes in conventional single gel culture did not
      completely regain their normal morphology and rapidly underwent progressive
      dedifferentiation. This was characterized by loss of cell polarization in terms
      of obliteration of the bile canaliculi-like intercellular expansions, loss of
      cell membrane differentiations, and reduction of organelles. Cytoskeletal
      components gradually increased, building up large filamentous zones underneath
      the plasma membrane. In double gel culture, the hepatocytes reachieved and
      maintained intact morphology and polarity over at least 14 days. The bile
      canaliculi were formed, preserved, or even enlarged and were associated with
      dense peribiliary bodies and Golgi fields. The plasma membrane facing both
      collagen layers bore numerous cytoplasmic microprojections like the sinusoidal
      surfaces of the hepatocytes in situ. Cell organelles, glycogen particles, and
      lipid droplets were always present. CONCLUSIONS: The hepatocyte is a cell type in
      which ultrastructural and functional differentiation are strongly interdependent.
      For these cells, the morphological microenvironment (i.e. the bipolar position of
      the extracellular matrix) may be as important or even more decisive for
      maintenance of normal cell differentiation than modifications of the composition
      of the matrix itself or addition of other cell types, as focused in other
      studies.

PMID- 7573977
TI  - Distribution of epithelioid cells in the wall of the chicken aorta and their
      functional role as chemoreceptors.
AB  - BACKGROUND: The ultrastructural characteristics of epithelioid cells in the wall
      of the chicken aorta have been studied by several investigators. Their
      characteristics were homologous to those of carotid body type I cells and are
      considered to be one of the peripheral chemoreceptors. However, there are few
      descriptions about their location, distribution, and how they react to chemical
      signals, nor have there been many reports about the localization of bioactive
      substances in the epithelioid cells. Therefore we designed this investigation to
      address these problems. METHODS: Wholemount immunohistochemistry using
      antiserotonin antiserum, scanning (SEM), and transmission (TEM) electron
      microscopy were used to observe the epithelioid cells and the lumen of the
      chicken aorta. The localizations of bioactive substances in the epithelioid cells
      were immunohistochemically investigated using 11 antisera. RESULTS: Epithelioid
      cells were dispersed in the wall of the aorta, forming a band approximately 1 mm
      in width, located 10 mm proximal to the confluence of the right and left
      ligamenta arteriosa. Serotonin, chromogranin, and neuron specific enolase
      immunoreactivities were detected in the epithelioid cells. SEM observations
      clearly demonstrated intraendothelial fenestrations, 1-3 microns in diameter, on
      the endothelial surface of the region of the band of epithelioid cells. TEM
      observations revealed that these fenestrations corresponded to endothelial gaps,
      directly beneath which epithelioid cells were sometimes located. CONCLUSIONS: The
      epithelioid cells are in direct access to the aortic lumen through endothelial
      fenestrations. Thus they may be able to perceive chemical signals from arterial
      blood directly.

PMID- 7573982
TI  - Comparison of left and right vertebral artery intracranial diameters.
AB  - BACKGROUND: The vertebral artery is vulnerable to mechanical injury, especially
      in the region of the first and second cervical vertebrae, with resultant thrombus
      and/or emboli formation, often found at the vertebro-basilar junction. Such
      vascular injuries and associated neurological insults have been documented
      repeatedly in the literature as following cervical spine manipulation, when
      movements of the head and neck can cause compression and/or stretching of the
      vertebral artery and alterations in its blood flow. This has particular clinical
      relevance if a patient has a hypoplastic vertebral artery. Such persons may be
      considered at risk as regards vascular accidents following manipulation of the
      cervical spine. The aim of this study was to measure and compare the intracranial
      diameters of the left and right vertebral arteries in groups of black and white
      male and female South African subjects. METHODS: Cadaver material from 58
      specimens was processed for light microscopy, and measurements of inner (lumen
      only) and outer (lumen, tunica intima, and tunica media) diameters taken and
      compared, using the t-test. RESULTS: Data analysis revealed a significant
      difference between the left and right vertebral artery intracranial diameters in
      the white female group only (N = 8). CONCLUSIONS: Such a statistically
      significant difference implies a difference of biological importance and it is
      suggested that this particular group of subjects may be a high-risk group as
      regards vascular accidents following cervical spine manipulation.

PMID- 7573983
TI  - Anatomy of the sinus node, AV node, and His bundle of the heart of the sperm
      whale (Physeter macrocephalus), with a note on the absence of an os cordis.
AB  - BACKGROUND: Atrioventricular (AV) conduction time in large whales is only
      slightly greater than in smaller mammals even though their hearts are enormously
      larger. Little is known of the detailed histology or cytology of the conduction
      system of large whales. Such knowledge could be useful in defining the nature of
      cardiac rhythm and conduction of the whale as well as smaller mammals including
      humans. METHODS: We studied hearts from seven sperm whales. After fixation in
      formaldehyde and later dissection, specimens were prepared for histological
      examination. RESULTS: Cell size, histological organization, and innervation of
      the sperm whale's sinus node, AV node, and His bundle are similar to most
      mammalian hearts, except the sinus node is substantially larger. There is no
      central fibrous body between the atrial and ventricular septa, and the whale has
      no os cordis. Only the upper quarter of the interventricular septum is fully
      formed; below that there is only a thin layer of fatty connective tissue between
      the two ventricles. CONCLUSIONS: Given our morphological findings, we believe
      that the whale's comparatively short AV conduction time may be best explained by
      the sinus node and AV node functioning as coupled relaxation oscillators. Absence
      of an os cordis or central fibrous body or strong attachment between the two
      ventricles may pose both electrophysiological and hemodynamic hazards when the
      whale is no longer in its normally buoyant aquatic environment.

PMID- 7573984
TI  - Histamine release from Weibel-Palade bodies of toad aortas induced by endothelin
      1 and sarafotoxin-S6b.
AB  - BACKGROUND: Endothelin-1 (ET-1) and sarafotoxin-S6b (STX) induce a remarkable
      degranulation of Weibel-Palade (WP) bodies prior to the vasocontraction of toad
      aortas. As WP bodies play the role of a reservoir site of the histamine in the
      endothelial cells, there is the possibility that ET-1 and STX evoke the release
      of histamine from WP bodies of this vessel. METHODS: Histamine concentrations
      were assayed by high-performance liquid chromatography (HPLC) from the perfusate
      after being perfused with a solution containing ET-1 and STX. Each vessel was
      fixed and embedded for conventional electron microscopy and immunoelectron
      microscopy using antihistamine sera. RESULTS: The appreciable concentrations of
      histamine were assayed by HPLC from the perfusate after the toad aortas were
      perfused with a solution containing ET-1 and STX. The immunoelectron microscopy
      revealed that histamine immunoreactive gold particles in the WP bodies remarkably
      decreased in number in the treated samples when compared to the control ones. Our
      immunoelectron micrographs indicated that the release of histamine from the
      endothelial cells occurred in association with the degranulation and the
      exocytosis of the WP bodies after treatment with ET-1 and STX. CONCLUSIONS: The
      present study clearly shows that ET-1 and STX induce the histamine release from
      WP bodies of the toad aortas by means of HPLC and immunoelectron microscopy.
      Histamine discharged from the WP bodies may be involved in the vasocontraction
      evoked by ET-1 and STX.

PMID- 7573985
TI  - Microcirculation of gills and accessory respiratory organs of the walking catfish
      Clarias batrachus.
AB  - BACKGROUND: An ability to extract oxygen directly from the atmosphere enables air
      breathing fish to survive otherwise debilitating hypoxic environments. Addition
      of accessory respiratory organs (ARO) necessitates changes in both the general
      circulatory system and the microcirculation of the respiratory epithelia.
      Understanding these modifications provides information on the efficiency of gas
      exchange organs as well as an indication of the evolutionary processes associated
      with adaptation to terrestrial habitats. METHODS: Vascular organization and
      structure of gills and ARO of the facultative air-breathing walking catfish
      Clarias batrachus were examined by scanning electron microscopy of vascular
      replicas and fixed tissue. RESULTS: Well-developed filaments are present on all
      four pairs of gill arches and they possess three vascular pathways: respiratory
      (arterioarterial), nutrient (arteriovenous), and interlamellar (arteriovenous),
      typical of teleosts. ARO, consisting of gill fans, dendritic organs on the second
      and fourth gill arch, and the suprabranchial epithelium are derived from gill
      tissue and retain structural features and arterioarterial vessels similar to gill
      filaments. Gill and ARO vessels are in parallel with each other, and together
      they are in series with the systemic circulation. Nutrients and interlamellar
      vessels are reduced in ARO. CONCLUSIONS: Other than the presence of multiple
      ventral aortas, and an additional vessel connecting the suprabranchial epithelium
      to the dorsal aorta, there are no vascular shunts or anatomical modifications
      that indicate spatial separation of flow through the heart or between gills and
      ARO. However, a mechanism is proposed that would prevent unsaturation of dorsal
      aortic blood by local myogenic vasoconstriction of gill vessels when the fish is
      in hypoxic water. Despite considerable differences in the gross features of ARO
      in Clarias and Heteropneustes fossilis (Olson et al. 1990 J. Morphol., 203:165),
      there are striking similarities in vascular organization and respiratory islet
      structure that suggest these ARO evolved in a common silurid ancestor and were
      later modified into an everted arborescent organ or inverted air sac,
      respectively.

PMID- 7573986
TI  - Macrophage-lymphocyte cell clusters in the hypothalamic ventricle of some
      elasmobranch fish: ultrastructural analysis and possible functional significance.
AB  - BACKGROUND: Previous studies have demonstrated the existence of lympho
      haemopoietic tissue in the meninges and choroid plexuses of various primitive
      vertebrates, including the stingray Dasyatis akajei and in early human embryos.
      In the present study, we extend these results analyzing macrophage-lymphocyte
      cell clusters found in the floor of the hypothalamic ventricle of several
      specimens of elasmobranchs. METHODS: After aseptical isolation of the brain from
      several specimens of smooth dogfish Triakis scyllia, cloudy dogfish Scyliorhinus
      torazame, gummy shark Mustelus manazo, and stingray Dasyatis akajei their
      hypothalamic regions were processed routinely by light, scanning, and
      transmission electron microscopy. RESULTS: The study of serial histological
      sections demonstrated that the macrophage-lymphocyte cell clusters proceeded from
      the meningeal lymphohaemopoietic tissue, reaching the ventricular lumen along
      large blood vessels. In this tissue, macrophages, different sized lymphocytes,
      lymphoblasts, granulocytes, monocytes, and developing and mature plasma cells
      were closely packed among a meshwork of fibroblastic reticular cell processes. It
      never invaded the brain parenchyma. A cell layer of glial elements and a
      continuous basement membrane interposed between the lymphoid tissue and the
      neural elements although some macrophages had migrated across the ependymal cell
      layer. In the ventricular lumen very irregular macrophages with long cell
      processes and containing abundant engulfed material of unknown origin formed big
      cell clusters with neighboring lymphocytes, lymphoblasts, and plasma cells,
      similar to those described during the immune response. Moreover, electron lucent
      cells which resembled the antigen-presenting cells of higher vertebrates
      established intimate surface cell contacts with the surrounding lymphocytes. In
      the third ventricle of several specimens of gummy shark, Mustelus manazo,
      morphologically similar cell clusters appeared but these were not connected to
      the meningeal lympho-haemopoietic tissue. No intraventricular cell aggregates
      were found in the stingray brain. CONCLUSIONS: Although we cannot rule out that
      these macrophage-lymphocyte cell clusters represent a permanent structure in the
      elasmobranch brain they rather seem to be only established after specific
      stimulation for preventing the entrance of noxious, foreign materials into the
      elasmobranch brain parenchyma.

PMID- 7573989
TI  - Chronic corticosterone treatment-induced ultrastructural changes at rat
      neuromuscular junction.
AB  - BACKGROUND: Chronic exposure to glucocorticoids affects both the structure and
      function of vertebrate skeletal muscles. As little is known about the effects of
      such steroids on the neuromuscular junctions (NMJs) of different muscle fiber
      types, the influence of chronic corticosterone (CORT) administration on the
      ultrastructure of NMJs of soleus (SOL) and extensor digitorum longus (EDL) was
      studied. METHODS: Ten Fischer 344 male rats, the same animals used previously,
      were either injected daily with 5-10 mg CORT or received vehicle as control
      animals for 3 months and were sacrificed at 5 months of age. Muscles were bathed
      in situ in 4% phosphate buffered glutaraldehyde for ten minutes, then removed and
      conventional electron microscopic procedures were followed. Qualitative and
      quantitative observations of nerve terminal ultrastructures were statistically
      treated with multivariate analysis of variance to determine differences between
      control and CORT-treated animals. RESULTS: Fast-twitch EDL muscles were more
      affected by CORT-treatment than slow-twitch SOL muscles. Morphometric analysis of
      NMJ's in CORT-treated rats revealed significant decrease in fiber diameter, nerve
      terminal area and synaptic vesicle density, but a significant increase in
      synaptic cleft (P < 0.05). The NMJ's underwent partial denervation and
      reinnervation processes as demonstrated by large areas of presynaptic nerve
      terminal occupied by microtubules and electron dense granular material.
      CONCLUSIONS: Chronic CORT-treatments induced degenerative changes which were more
      pronounced in fast-twitch EDL muscles than slow-twitch SOL muscles, suggesting
      that pattern or amount of activity affect the CORT-treatment outcome. These
      steroid-induced stress changes are similar to those observed in aging and disuse
      studies of NMJ. Thus, glucocorticoid hormones may play an etiological role in the
      homeostasis of the NMJ in response to various stimuli.

PMID- 7573988
TI  - Metamorphic shortening of the alimentary tract in anuran larvae (Rana
      catesbeiana).
AB  - BACKGROUND: The premetamorphic alimentary tract in anurans can be more than 10
      times a tadpole's body length but then dramatically shortens to a third or less
      of that length by the end of metamorphosis. Although there have been many studies
      on histological changes in the anuran gut with metamorphosis, the broader
      question of where the major shortening occurs has not been previously addressed.
      This topic is investigated here. METHODS: We began our study by labeling
      intestinal coils in situ in preserved Rana catesbeiana tadpoles and then
      uncoiling their intestines, locating, and measuring the labeled points. This
      allowed us to map the coiled gut of the tadpole, such that the distance along the
      oral-anal axis could be determined by simply counting coils. We next implanted
      markers into the intestinal coils of live R. catesbeiana tadpoles at five known
      locations along the oral-anal axis, established from the prior mapping. The
      tadpoles were then induced to metamorphose by immersion in thyroid hormone. After
      the gut had shortened to a third of its premetamorphic length, the positions of
      the implanted markers were determined through dissection. RESULTS: Relative
      distances between the marked points did not change when the gut shortened.
      CONCLUSIONS: The results indicate that during metamorphosis the intestine
      shortens uniformly along its length and not preferentially from one region or
      another. Although metamorphosis was artificially induced, the shortening that we
      observed matches that occurring during natural metamorphosis.

PMID- 7573987
TI  - Corrosion casting study on the vasculature of nasal mucosa in the human fetus.
AB  - BACKGROUND: The vasculature of the nasal mucosa in the human fetus so far has not
      been investigated morphologically by modern techniques. METHODS: Nasal blood
      vessels were studied in 18-21-week-old human fetuses by corrosion casting and
      scanning electron microscopy. RESULTS: The general vascular architecture was
      similar to that described for adult humans, with (1) a dense network of
      subepithelial capillaries, (2) a mucosal layer of larger vessels, predominantly
      veins, and (3) large arteries located near the perichondrium. Specific vessel
      types characteristic of the nasal mucosa and important for its functions in
      adults, such as cavernous veins or cushion veins, were, however, absent in the
      fetuses, although probable precursor forms of cushion veins could be observed.
      The arteriovenous anastomoses had the form of short bridges, and no tortuous or
      glomerular anastomoses present in the mature nasal mucosa were found.
      CONCLUSIONS: The underdevelopment of some vascular areas is postulated to reflect
      the functional immaturity of the respiratory system in the fetus.

PMID- 7573990
TI  - Drug delivery system to improve the perioperative administration of intravenous
      drugs: computer assisted continuous infusion (CACI)

PMID- 7573991
TI  - Memory during anesthesia: gone but not forgotten?

PMID- 7573992
TI  - Computer-controlled infusion of alfentanil versus patient-controlled
      administration of morphine for postoperative analgesia: a double-blind randomized
      trial.
AB  - This study compared the efficacy of computer-controlled infusion of alfentanil
      (CCiA) with patient-controlled administration of morphine (PCAM) for
      postoperative analgesia. Twenty patients were randomly allocated to one of the
      two study groups to receive either an intravenous CCiA or PCAM regimen. Pain
      scores measured on a visual analog scale (VAS) and the number of valid demands
      were used as variables to evaluate the efficacy of the postoperative analgesic
      therapy. In addition, the bias and inaccuracy of the pharmacokinetic data set of
      alfentanil used in the CCiA program were examined by determining the median
      performance error (MDPE), and the median absolute performance error (MDAPE). The
      onset of satisfactory analgesia was faster (P < 0.05) in the CCiA group (median:
      20 min) than in the PCAM group (median: 50 min). The total number of demands was
      lower (21 vs 34, P < 0.05) and the time when the VAS score was > 3.0 was shorter
      (P < 0.05, 12% of the time) in the CCiA group than in the PCAM group (21% of the
      time). The MDPE and MDAPE were 8% and 22%, respectively. The maximum alfentanil
      concentrations associated with pain and the minimum effective analgesic
      concentrations of alfentanil varied considerably both inter- and
      intraindividually. In conclusion, compared to a standard intravenous PCAM
      regimen, a CCiA is faster in onset of analgesia and is as effective in providing
      postoperative analgesia.

PMID- 7573993
TI  - Coagulopathies in patients after transurethral resection of the prostate: spinal
      versus general anesthesia.
AB  - This prospective, randomized study evaluated the effects of spinal versus general
      anesthetic technique on perioperative blood loss and the development of
      postoperative coagulopathies in 50 patients undergoing transurethral resection of
      the prostate (TURP). Preoperative hematologic measurements included hemoglobin,
      platelet count, electrolytes, prothrombin time, partial thromboplastin time,
      fibrinogen, factor V, plasminogen, antithrombin III, and fibrinogen degradation
      product (FDP) levels. All hematologic blood samples wre repeated postoperatively
      at 1, 6, and 24 h. Intraoperative blood loss was not significantly different
      between the spinal and general anesthesia groups. The total blood loss after TURP
      was significantly correlated (r = 0.76; P < 0.0001) with the prostatic tissue
      weight. When the tissue weight resected exceeded 35 g, blood loss was in excess
      of the linear correlation shown with the weight of resected prostatic tissue.
      Platelet count decreased and prothrombin time increased in the spinal group at
      all postoperative time intervals compared to preoperative value (P < 0.05). There
      was no significant difference in measured coagulation variables (fibrinogen,
      factor V, plasminogen, antithrombin III, and FDP) between the spinal and general
      anesthesia groups, but there were significant decreases in postoperative
      fibrinogen and Factor V levels compared to preoperative values in both spinal and
      general anesthesia groups. Three patients (6%) had increased FDP levels 1 h
      postoperatively. The prostatic tissue weight and the surgical duration was
      significantly higher in these patients. We conclude that perioperative blood loss
      in TURP patients is not affected by the anesthetic technique. However, 6% of TURP
      patients developed subclinical intravascular coagulopathies which correlated with
      mass of resected prostate tissue.

PMID- 7573994
TI  - A new axillary approach for continuous brachial plexus block. A clinical and
      anatomic study.
AB  - Catheter insertion in the neurovascular space by axillary approach allows a
      continuous brachial plexus block and/or postoperative analgesia. We developed a
      perivenous technique whereby the approach to the neurovascular sheath is guided
      under fluoroscopy by a preopacified axillary vein. A randomized study compared
      this technique to the technique of Selander in ASA grade I-II patients scheduled
      for surgery or painful physiotherapy of the hand. The study was performed in 36
      patients randomly divided into two groups. In Group 1 (n = 18), the catheter was
      placed according to the technique described by Selander. In Group 2 (n = 18), the
      catheter was placed using our perivenous technique. A complete block was obtained
      in all the patients of Group 2 vs only 50% of the patients in Group 1 (P < 0.05).
      In Group 1 a partial block was observed in 17%, with failure in 33% of the
      patients. There was no difference in the two groups regarding the time required
      to perform either technique, the duration of the complete block, the pain score,
      or the amount of continuously administrated bupivacaine during the first 48 h
      postoperatively. The plasma concentrations of total bupivacaine (high-performance
      liquid chromatography) were low in successful blocks, with no differences in the
      two groups; the median value was 0.68 microgram/mL (95% confidence interval: 0.62
      0.89). The concentrations were higher (P < 0.01) in failed blocks; the median
      value was 1.69 micrograms/mL (95% confidence interval: 0.58-2.8). A complementary
      anatomic study of three arms from fresh cadavers allowed verification of the
      correct localization of the Teflon cannula and flexible catheter, as well as
      homogeneous diffusion of the methylene blue inside the brachial plexus. The
      perivenous technique for continuous axillary brachial plexus block may improve
      the success rate due to its radiologic and accurate location of the neurovascular
      sheath.

PMID- 7573995
TI  - A retrospective comparison of spinal and general anesthesia for vaginal
      hysterectomy: a time analysis.
AB  - The authors sought to compare time efficiency of spinal versus general
      anesthesia. The charts of 106 consecutive patients who had undergone a vaginal
      hysterectomy were analyzed. This analysis divided the patients into three groups:
      Group 1, spinal anesthesia; Group 2, general anesthesia; Group 3, spinal
      anesthesia with subsequent general anesthesia. The perioperative time course was
      divided into six intervals from entry into the operating room to discharge from
      the postanesthesia care unit (PACU). Total time was calculated by adding the six
      intervals. There were 85 patients in Group 1, 17 patients in Group 2, and 4
      patients in Group 3. The mean times for surgical readiness once the
      anesthesiologist was present for Group 1, Group 2, and Group 3 were 21.4 +/- 7.3,
      21.4 +/- 6.0, and 25.0 +/- 5.8 min, respectively. The total time for the three
      groups was 278.3 +/- 72.0, 245.9 +/- 23.1, and 295.0 +/- 101.2 min, respectively
      (P < 0.01 Group 1 vs Group 2). The difference in total time between Groups 1 and
      2 was accounted for mainly by the stay in the PACU. This study concludes that
      there is no difference in the efficiency of operating room time use between
      spinal and general anesthesia.

PMID- 7573996
TI  - Comparison of 5% with dextrose, 1.5% with dextrose, and 1.5% dextrose-free
      lidocaine solutions for spinal anesthesia in human volunteers.
AB  - The use of lidocaine in concentrations less than 5% for spinal anesthesia may be
      advantageous but has not been carefully studied. Lidocaine 50 mg (1.5% with
      dextrose and 1.5% dextrose-free) was administered to eight volunteers in a
      randomized, double blind, cross-over fashion. All of these subjects had
      previously received 5% lidocaine with dextrose using the same experimental
      protocol. Sensory analgesia was assessed with pinprick, transcutaneous electrical
      stimulation (TES) equivalent to surgical incision, and duration of tolerance of
      pneumatic thigh tourniquet. Motor block was assessed with isometric force
      dynamometry. Peak dermatomal level was the highest and duration until regression
      of pinprick the longest with the 5% solution (P < 0.05). Duration of tolerance to
      TES was increased (33 +/- 10 min) with the 5% solution (P < 0.04). Duration of
      tolerance to tourniquet pain was increased (11 +/- 3 min) with the 5% solution (P
      < 0.02). Duration of motor block was increased (45 +/- 9 min) with the 5% and the
      1.5% without dextrose solutions (P < 0.04). Time to void was increased (33 +/- 5
      min) with the 5% solution (P < 0.03). In conclusion, the use of different
      solutions of lidocaine for spinal anesthesia results in significant differences
      in sensory and motor block and time until recovery of micturition.

PMID- 7573997
TI  - Ephedrine-induced increases in arterial blood pressure accelerate regression of
      epidural block.
AB  - We investigated the hypothesis that ephedrine-induced increases in blood pressure
      accelerate the regression of epidural block. In patients undergoing minor
      gynecologic surgery, we performed lumbar epidural blockade using 2% lidocaine
      containing 1:200,000 epinephrine to which was added 0.1 mg of fentanyl. Eighty
      minutes after the epidural injection, we started an ephedrine infusion to
      increase the systolic blood pressure by 20% in 10 min and maintained the value
      for the following 20 min. Then we compared the proximal extent of sensory
      analgesia at 80 min with that at 140 min. Ephedrine significantly (P = 0.001)
      hastened the regression of sensory analgesia. We conclude that an ephedrine
      induced blood pressure increase accelerates regression of epidural blockade.

PMID- 7573999
TI  - Systemic adenosine infusion alleviates spontaneous and stimulus evoked pain in
      patients with peripheral neuropathic pain.
AB  - In seven patients with peripheral neuropathic pain, the effect of systemic
      adenosine infusion on pain symptoms was evaluated in a double-blind, placebo
      controlled, cross-over study. The study infusions, adenosine (50 micrograms.kg
      1.min-1) or placebo, were given intravenously (IV) during 45-60 min at two
      separate occasions. Before and during infusions, bedside examination of
      sensibility and quantitative sensory testing (QST), i.e., assessments of
      perception thresholds for touch, touch-evoked pain, cold, warmth, painful heat,
      and cold, were performed. In the neuropathic area, sensation magnitude was rated
      by a visual analog scale (100 mm VAS) using a pin and at perception threshold for
      touch-evoked pain using von Frey filaments. Adenosine infusion reduced
      spontaneous pain (P < 0.05), and caused an increase of the touch-evoked pain
      threshold from 10.8 +/- 5.3 to 22.2 +/- 6.9 g (P < 0.05), whereas placebo had no
      effect. Pain intensity at perception threshold for touch-evoked pain was,
      however, unaltered. Pinprick-evoked pain in the neuropathic areas was reduced
      from 53 +/- 11 to 29 +/- 10 mm (P < 0.05). No other sensory modality was
      consistently changed during adenosine infusion. In conclusion, the present study
      demonstrates that adenosine infusion alleviates spontaneous neuropathic pain,
      tactile allodynia, and pinprick hyperalgesia in patients with peripheral
      neuropathic disorders, probably by a central mechanism of action.

PMID- 7574000
TI  - Intravenous regional guanethidine in the treatment of reflex sympathetic
      dystrophy/causalgia: a randomized, double-blind study. Guanethidine Study Group.
AB  - This double-blind, randomized, multicenter study was designed to determine the
      short-term and long-term efficacy of intravenous regional block with guanethidine
      in patients with reflex sympathetic dystrophy (RSD)/causalgia. Sixty patients
      were enrolled to receive four intravenous regional blocks at 4-day intervals with
      either guanethidine or placebo in 0.5% lidocaine. Each patient was randomized to
      receive either one, two, or four blocks with guanethidine. Follow-up visits were
      scheduled for 4 days, 1 mo, 3 mo, and 6 mo after their final block. At 4 days
      after the initial block, the group treated with placebo experienced a greater
      decrease in pain scores than those treated with guanethidine, although this
      difference was not statistically significant. On long-term followup there was no
      difference in pain scores between groups receiving one, two, or four guanethidine
      blocks. Overall, only 35% of patients experienced clinically significant relief
      on long-term followup even though all were treated early in the evolution of RSD.

PMID- 7574001
TI  - Cocaine, lidocaine, tetracaine: which is best for topical nasal anesthesia?
AB  - The quality of nasal anesthesia obtained with three local anesthetic solutions
      (4% cocaine, 2% lidocaine in oxymetazoline, and 1% tetracaine in oxymetazoline)
      was evaluated in a randomized study. Each local anesthetic mixture was applied to
      the nasal septum of healthy volunteers using medication-soaked pledgets.
      Measurements of anesthetic effect (sensation threshold and pain perception) were
      made with Semmes-Weinstein monofilaments. Measurements were performed prior to
      local anesthetic application and 10 and 70 min after local anesthetic
      application. Subjects had greater increases in sensation threshold with
      tetracaine than with lidocaine or cocaine at both 10 and 70 min (P < 0.05).
      Subjects had greater decreases in pain perception with tetracaine than with
      lidocaine or cocaine at both time intervals (P < 0.05). Tetracaine mixed with
      oxymetazoline appears to be a superior topical anesthetic for nasal procedures.

PMID- 7573998
TI  - Comparison of intravenous and epidural clonidine for postoperative patient
      controlled analgesia.
AB  - Both epidural and intravenous clonidine are used to provide postoperative
      analgesia, but in predetermined doses. This double-blind randomized study was
      designed to 1) determine the clonidine dose inducing pain relief after major
      orthopedic surgery, when controlled by patient, either intravenously or
      epidurally; and 2) assess whether these two administration routes are clinically
      equivalent. At the first complaint of pain after scoliosis correction, patients
      received an initial dose of 8 micrograms/kg clonidine during 30 min either
      intravenously (n = 12) or epidurally (n = 12). Then, clonidine was given using a
      patient-controlled analgesia pump via the corresponding administration route. In
      both cases, the bolus dose was set at 30 micrograms and the lockout interval at
      15 min. Pain (0-100 scale), clonidine requirements, sedation (0-4 scale), and
      hemodynamics (by fiberoptic pulmonary artery catheter) were measured before and
      15, 30, 120, 240, 360, 480, and 600 min after the loading dose was started.
      Plasma clonidine concentrations and arterial blood gases were determined at the
      15th, 30th, 240th, and 480th min. Self-administered and total clonidine doses
      were larger in the intravenous group than in the epidural group (at 600 min: 372
      +/- 110 vs 235 +/- 144 micrograms, and including the initial dose, 814 +/- 114 vs
      652 +/- 187 micrograms; mean +/- SD). Clonidine administration resulted in pain
      relief and sedation in both groups but, for comparable pain relief, sedation
      scores were lower in the epidural group. No intergroup differences in hemodynamic
      data were observed, although the decrease in blood pressure occurred earlier in
      the intravenous group. Plasma clonidine concentrations were higher in the
      intravenous group than in the epidural group (2.5 +/- 0.6 vs 1.5 +/- 0.5 ng/mL
      after the initial dose and 2.1 +/- 0.5 vs 1.5 +/- 0.4 ng/mL during self
      administration; mean +/- SD). We conclude that analgesia can be achieved
      postoperatively by both epidural and intravenous clonidine administration. The
      epidural route is associated with significant reductions in self-administered
      clonidine dose, and thus in the plasma clonidine concentration, and the level of
      sedation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574002
TI  - Subanesthetic concentrations of desflurane and propofol suppress recall of
      emotionally charged information.
AB  - Whether anesthetized patients register emotionally charged information remains
      controversial. We tested this possibility using subanesthetic concentrations of
      propofol or desflurane. Twenty-two volunteers (selected for hypnosis
      susceptibility) received propofol and desflurane (on separate occasions, and in a
      random order) at a concentration 1.5-2 times each individual's minimum alveolar
      anesthetic concentration (MAC)-awake (or equivalent for propofol). We gave
      vecuronium, intubated the trachea of each volunteer, controlled ventilation, and
      then presented a neutral (control) drama or a "crisis" drama stating that the
      oxygen delivery system had failed, assigning crisis and control dramas in a
      blinded, randomized, and balanced manner. One day later, interviewers blinded to
      the assigned drama conducted a 2-h structured interview (including hypnosis) to
      determine whether the contents of the interviews after crisis and control dramas
      differed. In addition, messages permitting subsequent assessment of learning of
      matter-of-fact information (Trivial Pursuit-type question task and a behavior
      task) were presented at the anesthetic concentration just sufficient to prevent
      response to command in each volunteer. No analyses of the tasks involving matter
      of-fact information revealed learning except one which correlated hypnosis
      susceptibility with behavior task performance. Both propofol and desflurane
      suppressed memory of the crisis. Consistent with previous findings for isoflurane
      and nitrous oxide, propofol and desflurane suppressed learning of matter-of-fact
      information at concentrations just above MAC-awake, except that volunteers'
      susceptibility to hypnosis correlated with performance of a behavior suggested
      during anesthesia. Propofol and desflurane suppressed learning of emotionally
      charged information at anesthetic concentrations 1.5-2 times MAC-awake (less than
      MAC), a different result from that previously reported for ether.

PMID- 7574003
TI  - Concentrations of desflurane and propofol that suppress response to command in
      humans.
AB  - The anesthetic concentration just suppressing appropriate response to command
      (minimum alveolar anesthetic concentration awake [MAC-awake] for volatile
      anesthetics or plasma concentration to prevent a response in 50% of patients
      [Cp50]-awake for intravenous anesthetics) provides three important measures.
      First, along with pharmacokinetics, the ratio of the awakening concentration to
      the anesthetizing concentration (MAC-awake/MAC or Cp50-awake/Cp50) determines
      time to awakening. Second, a correlation between MAC-awake and the anesthetic
      concentration sufficient to prevent learning suggests MAC-awake provides a
      surrogate measure of amnestic potency. Third, population values for MAC-awake
      provide evidence for or against commonality in anesthetic mechanisms. We studied
      22 male volunteers twice to determine both MAC-awake for desflurane (2.60% +/-
      0.46%) and Cp50-awake for propofol (2.69 +/- 0.56 microgram/mL). Awakening with
      desflurane occurs at a concentration closer to its anesthetizing concentration
      (36% of MAC) than propofol (18% of Cp50); that is, 1) desflurane requires less of
      a decrement in anesthetic concentration at the effect site for arousal; and 2) if
      MAC-awake (Cp50-awake) values reflect the concentrations providing amnesia,
      propofol is a more potent amnestic. Of interest, the dose response curves of
      desflurane and propofol were equivalently steep, a finding consistent with a
      common mechanism of action. In contrast, sensitivity of each volunteer to
      desflurane did not correlate with sensitivity to propofol (r2 < 0.01, P = 0.98)
      arguing against a common mechanism.

PMID- 7574004
TI  - The effects of increased abdominal pressure on lung and chest wall mechanics
      during laparoscopic surgery.
AB  - We tested the hypothesis that increases in pressure in the abdomen (Pab) exerted
      by CO2 insufflation during laparoscopy would increase elastance (E) and
      resistance (R) of both the lungs and chest wall. We measured airway flow and
      airway and esophageal pressures of 12 anesthetized/paralyzed tracheally intubated
      patients during mechanical ventilation at 10-30/min and tidal volume of 250-800
      mL. From these measurements, we used discrete Fourier transformation to calculate
      E and R of the lungs and chest wall. Measurements were made at 0, 15, and 25 mm
      Hg Pab in the 15 degrees head-down (Trendelenburg) posture and at 0 and 15 mm Hg
      Pab in the 10 degrees head-up (reverse Trendelenburg) posture. Lung and chest
      wall Es and Rs while head-down increased at Pab = 15 mm Hg, and both Es increased
      further at Pab = 25 mm Hg (P < 0.05). Both Es and Rs also increased while head-up
      at Pab = 15 mm Hg (P < 0.05), but increases in lung E and R were less than while
      head-down (P < 0.05). The increase in lung E and R at Pab = 15 mm Hg in either
      posture were positively correlated to body weight or body mass index, whereas the
      increases in chest wall E and R were negatively correlated to the same factors (P
      < 0.05). Lung and chest wall mechanical impedances increase with increasing Pab;
      the increases depend on body configuration and are greater while head
      down.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574005
TI  - Does sleep enhance the effect of subanesthetic isoflurane on hypoxic ventilation?
AB  - After surgery, patients may receive little audiovisual stimulation and may sleep.
      Lack of audiovisual stimulation enhances the suppression of the hypoxic
      ventilatory response (HVR) by 0.1 minimum alveolar anesthetic concentration (MAC)
      isoflurane. Sleep also reduces the HVR and may thus increase the risk of hypoxia
      in patients at this time. We therefore measured the ventilatory response in
      volunteers to a sustained step hypoxic stimulus (mean arterial oxygen saturation
      [SaO2] 80% [SEM 0.3] for 20 min) in the presence of 0.1 MAC isoflurane, with
      subjects in the awake and asleep states. The behavioral states were studied in
      random order in nine male subjects. The combination of isoflurane and sleep
      significantly reduced (P < 0.05) normoxic ventilation (6.71 [0.39] vs 8.24 [0.29]
      L/min) and increased end-tidal PCO2 (PETCO2) (43.1 [0.5] vs 40.4 [0.8] mm Hg)
      compared with the awake state. However, ventilation was similar in the asleep and
      awake states during early (15.10 [1.35] vs 15.50 [1.61] L/min) and late (10.45
      [0.97] vs 11.03 [0.99] L/min) hypoxia in the presence of isoflurane. Thus sleep
      did not reduce ventilation during hypoxia in the presence of isoflurane sedation.
      The increase in PETCO2 during sleep may have offset suppression of the HVR.

PMID- 7574006
TI  - The incidence of venous emboli during extramedullary guided total knee
      arthroplasty.
AB  - During total knee arthroplasty (TKA), instrumentation of the marrow cavity with
      an intramedullary guide appears responsible for fatal intraoperative pulmonary
      embolism. Transesophageal echocardiography demonstrates venous emboli (VE) after
      tourniquet deflation during intramedullary guided TKA. Extramedullary guides
      avoid manipulating the marrow cavity. We determined the incidence of VE in 20
      patients undergoing extramedullary guided TKA. Recordings of hemodynamic
      variables, mixed venous oximetry, end-tidal CO2 and N2 tensions, and
      echocardiograph images occurred after induction of anesthesia, after tourniquet
      inflation, during cementing, and for 15 min after tourniquet deflation. Large VE
      appeared in 14 patients and small VE in the other 6 patients. Large VE occurred
      only after deflation of the tourniquet. Beginning 3 min after tourniquet
      deflation, mean pulmonary arterial pressures increased from the baseline of 21 +/
      1.0 to 30 +/- 1.3 mm Hg and remained increased for the duration of the
      procedure. The incidence of large VE with extramedullary guided TKA did not
      differ compared to the previously reported incidence with intramedullary guided
      TKA. These data suggest that VE might arise from a thrombogenic effect of the
      tourniquet rather than from manipulation of the marrow cavity.

PMID- 7574007
TI  - Some effects of d-tubocurarine alone and combined with halothane or isoflurane on
      neuromuscular transmission.
AB  - The mechanisms contributing to the neuromuscular block produced by
      nondepolarizing muscle relaxants and inhaled anesthetics include: 1) receptor
      blockade, 2) open or closed ion channel block, 3) decreased transmitter release,
      and 4) receptor desensitization. In this study we investigated the contributions
      of receptor and ion channel block. We used the two microelectrode voltage clamp
      to evaluate miniature end-plate currents (MEPCs) for amplitude and time constant
      of decay (tau) before and after the application of 1) d-Tubocurarine (DTC) (10(
      7)-10(-6) M) alone, and then 2) the same concentration of DTC plus 0.5% or 1.0%
      halothane or isoflurane delivered by passing compressed air through a flow and
      temperature compensated vaporizer. The electrodes were maintained in the same
      cell for the entire experiment. DTC alone decreased MEPC amplitude to 91.3% +/-
      4.5% and 65.1% +/- 5.6% of control at 10(-7) and 10(-6) M, respectively. MEPC
      amplitude with 10(-6) M DTC decreased further to 52.4% +/- 7.6% and 37.4% +/-
      7.0% of control after the addition of 0.5% and 1.0% halothane, respectively.
      After the application of DTC 10(-7) M tau was 94.7% +/- 3.1% of control and
      decreased to 73.7% +/- 7.1% of control with 10(-6) M DTC. After the application
      of DTC 10(-6) M the addition of 0.5% and 1% halothane decreased tau to 52.4% +/-
      7.6% and 30.0% +/- 5.9% of control. Isoflurane produced similar changes. This
      study provides evidence that at least some of the augmentation of nondepolarizing
      relaxants by inhaled anesthetics can be explained by the additive effect of
      nondepolarizing muscle relaxants and inhaled anesthetics on MEPC amplitude and
      tau.

PMID- 7574008
TI  - Interaction of decamethonium with hexamethonium or vecuronium in the rat: an
      isobolographic analysis.
AB  - We used isobolographic analysis to investigate the interaction of decamethonium
      with either hexamethonium or vecuronium in the rat phrenic nerve hemidiaphragm
      preparation. EC50 values of decamethonium, hexamethonium, and vecuronium were
      (mean +/- SEM) 47.36 +/- 9.58 microM, 4.27 +/- 0.53 mM, and 5.19 +/- 1.17 microM,
      respectively. Combinations of drugs in concentrations corresponding to the 1:2,
      1:1, and 2:1 ratios of their EC50 values were used to determine three points of
      each isobole. Decamethonium and hexamethonium showed antagonism: significant
      deviations from the line of additivity were found at EC50 ratios of 2:1 and 1:1
      (P < 0.01 and P < 0.05, respectively) indicating that hexamethonium is a potent
      antagonist of decamethonium. For decamethonium and vecuronium none of the three
      points on the isobole was significantly different from the corresponding point on
      the line of additivity. Hexamethonium is known to be a weak antagonist at the
      postsynaptic nicotinic acetylcholine receptor but a potent antagonist at the
      presynaptic nicotinic receptor. Vecuronium is a more potent antagonist at the
      postsynaptic nicotinic receptor but a much weaker antagonist at the presynaptic
      site. It was postulated that in the rat the primary site of action of
      decamethonium is at the presynaptic nerve terminal. Our findings suggest that
      presynaptic rather than postsynaptic potency of a nondepolarizing drug determines
      ability to antagonize the effect of a depolarizing drug in the rat.

PMID- 7574009
TI  - Aging alters the pharmacokinetics of pyridostigmine.
AB  - The duration of the antagonism to neuromuscular blockade produced by
      pyridostigmine is prolonged in elderly patients, and a pharmacokinetic
      explanation was sought. Ten elderly (71-85 yr) and 10 younger (21-51 yr) patients
      were anesthetized with thiopental, nitrous oxide, and isoflurane and paralyzed
      with a combination of d-tubocurarine and pancuronium. When twitch height returned
      to 5% of baseline, pyridostigmine 0.25 mg/kg was administered and blood samples
      were collected intermittently for 6 h. Pyridostigmine plasma concentrations were
      determined by radioimmunoassay and after an hour were always greater in the
      elderly than in the younger patients. In both groups, plasma pyridostigmine
      decrement curves were best described by triexponential equations. Pharmacokinetic
      analysis revealed that plasma clearance in the elderly group was significantly
      decreased compared to that in the younger group (6.7 +/- 2.2 vs 9.5 +/- 2.7 mL.kg
      1.min-1, P < 0.05). Elimination half-lives and volumes of distribution were not
      significantly different between groups. We conclude that a possible explanation
      for the prolonged duration of action of pyridostigmine in the elderly is its slow
      plasma clearance.

PMID- 7574010
TI  - Mechanisms of increased myocardial contractility with hypertonic saline solutions
      in isolated blood-perfused rabbit hearts.
AB  - Hypertonic saline improves organ perfusion and animal survival during hemorrhagic
      shock because it expands plasma volume and increases tissue oxygenation. Because
      both decreased and increased myocardial performance have been reported with
      hypertonic saline, the effects of hyperosmolarity and the mechanism accounting
      for it were investigated in isolated blood-perfused rabbit hearts. Coronary blood
      flow (CBF), myocardial contractility, relaxation, and oxygen consumption were
      measured during administration of blood perfusates containing 140-180 mmol sodium
      concentrations ([Na+]). In two other series of experiments, the role of Na(+)
      Ca2+ exchange in the inotropic effect of hyperosmolarity (160 mmol sodium
      concentration) and hypertonicity (sucrose) were also investigated. Hypertonic
      [Na+] induced a significant increase in contractility and relaxation, combined
      with a coronary vasodilation. Myocardial oxygen consumption (MVO2) increased at
      all hypertonic [Na+] without significant change in coronary venous oxygen tension
      (PVO2) and content (CVO2). Amiloride (0.3 mmol) inhibited the improved
      contractility observed with 160 mmol sodium. Similar Na(+)-Ca2+ exchanger
      blockade did not inhibit the inotropic effect of sucrose. These results confirm
      the positive inotropic effect of hypertonic [Na+]. The inhibition of this
      improvement by amiloride suggests that calcium influx through the sarcolemna
      could be the major mechanism of this effect.

PMID- 7574011
TI  - A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults
      undergoing cardiac surgery.
AB  - Milrinone can reverse acute postischemic myocardial dysfunction after
      cardiopulmonary bypass, although neither the appropriate bolus dose nor its
      pharmacokinetics has been established for cardiac surgical patients. Consenting
      patients undergoing cardiac surgery received milrinone (25, 50, or 75
      micrograms/kg) in an open-label, dose-escalating study if their cardiac index was
      < 3 L.min-1.m-2 after separation from bypass. Heart rate, mean arterial blood
      pressure, pulmonary capillary wedge pressure, and cardiac index were determined
      before and after the administration of milrinone. Timed blood samples were
      obtained for measurement of milrinone plasma concentrations and pharmacokinetic
      analysis. Twenty-nine of 60 consenting patients had cardiac indices < 3 L.min-1.m
      2 after separation from bypass, received milrinone, and completed the protocol.
      All three bolus doses of milrinone significantly increased cardiac index. The 50-
      and 75-micrograms/kg doses produced significantly larger increases in cardiac
      index than the 25-micrograms/kg dose; however, the 75-micrograms/kg dose did not
      produce a significantly larger increase in cardiac index than did the 50
      micrograms/kg dose. Two of 10 patients receiving milrinone 25 micrograms/kg, but
      no patient receiving either 50 or 75 micrograms/kg, required early epinephrine
      rescue when the cardiac index failed to increase by > 15%. The 75-micrograms/kg
      dose was associated with a case of ventricular tachycardia. The three-compartment
      model better described milrinone drug disposition than the two-compartment model
      by both visual inspection and Schwartz-Bayesian criterion. There was only limited
      evidence of dose-dependence, so data from all three doses are reported together
      (and normalized to the 50-micrograms/kg dose). Data from one patient was
      discarded (samples mislabeled). Using mixed-effects nonlinear regression (for n =
      28), the following volumes were determined for the three compartments: V1 = 11.1
      L, V2 = 16.9 L, and V3 = 363 L. Similarly, the following clearances were
      estimated for the three compartments: Cl1 = 0.067 L/min, Cl2 = 1.05 L/min, and
      Cl3 = 0.31 L/min. The 50-micrograms/kg loading dose appeared more potent than the
      25-micrograms/kg dose, and, as potent, but with possibly fewer side-effects than
      the 75-micrograms/kg dose. The short context-sensitive half-times of 6.7 or 10.2
      min after 1- or 10-min bolus infusions underscore the need for prompt institution
      of a maintenance infusion when milrinone concentrations must be
      maintained.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7574012
TI  - The effect of midazolam on left ventricular pump performance and contractility in
      anesthetized patients with coronary artery disease: effect of preoperative
      ejection fraction.
AB  - Forty patients undergoing coronary artery bypass grafting were studied, of whom
      24 had depressed global left ventricular (LV) function at preoperative
      catheterization, to evaluate the effects of midazolam on LV pump performance and
      contractility. Transesophageal echocardiography and simultaneous hemodynamic
      measurements were used to assess LV preload, afterload, and systolic performance
      during inhalation of 100% O2 and after 0.1 mg/kg of midazolam. Systolic function
      indices were expressed as a percent of the predicted value for observed end
      systolic stress to estimate LV contractility. In the entire study population,
      midazolam did not affect cardiac index. Heart rate and mean arterial pressure
      were reduced (63 +/- 13 to 59 +/- 12 bm; P < 0.0006 and 89 +/- 15 to 76 +/- 16 mm
      Hg; P < 0.0001) as were pulmonary capillary wedge pressure, central venous
      pressure, and systemic and pulmonary vascular resistance. Afterload, as measured
      by end-systolic stress, was reduced (55 +/- 33 to 48 +/- 26 kdyne/cm2; P = 0.007)
      with no change in fractional shortening or percent area change. As a result,
      systolic function decreased in relation to observed end-systolic stress,
      providing evidence of reduced LV contractility. Thus, midazolam administration
      (0.1 mg/kg) caused no change in cardiac pump performance but decreased LV
      contractility in the entire population. Myocardial contractility was lower at
      baseline and after the administration of midazolam in the depressed ejection
      fraction group, but the decrease in contractility was not exaggerated in the
      depressed ejection fraction group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574013
TI  - Neuroanesthesia adjunct therapy (mannitol and hyperventilation) is as effective
      as cerebrospinal fluid drainage for prevention of paraplegia after descending
      thoracic aortic cross-clamping in the dog.
AB  - We compared cerebrospinal fluid (CSF) drainage (Group D; n = 8) to
      neuroanesthesia adjunct therapy (hyperventilation and mannitol administration;
      Group N; n = 8) for the prevention of paraplegia using a canine model of
      descending thoracic aortic cross-clamping (AXC; 2.5 mm distal to the left
      subclavian artery for 30 min). We expected no difference in neurologic outcome
      between groups. After surgical preparation and a 30-min stabilization period,
      dogs in Group D had CSF drained prior to application of the AXC. During the
      period of AXC, CSF was allowed to drain freely in an attempt to have
      cerebrospinal fluid pressure (CSFP) no greater than central venous pressure
      (CVP). Dogs in Group N were hyperventilated (PaCO2 28-32 mm Hg) and received 2
      g/kg of mannitol prior to AXC and then 1 g.kg-1.hr-1 during clamping. Systemic
      hemodynamics, CSFP, and arterial blood gases were measured at 1) baseline, 2) 2
      min after AXC, 3) 20 min after AXC, 4) 5 min after AXC release, and 5) 30 min
      after resuscitation. With release of the AXC, PaCO2 was not controlled in Group
      D; in Group N the minute ventilation was further increased to maintain PaCO2
      constant. At precisely 24 h after AXC, the animals were assessed for incidence
      and severity of paraplegia, using the Tarlov score, by an observer unaware of the
      experimental protocol. The animals were then killed, and the entire spinal cord
      was removed for histologic assessment. Multiple sections of the lumbar spinal
      cord were processed and stained with hematoxylin and eosin, then examined by
      light microscopy for nonviable neurons in the anterior spinal cord.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7574014
TI  - The arterial to end-tidal carbon dioxide difference in neurosurgical patients
      during craniotomy.
AB  - PETCO2 is often used as an estimate of PaCO2, with the understanding that PaCO2
      usually exceeds PETCO2. During intraoperative craniotomies, because
      hyperventilation is used to therapeutically lower intracranial pressure, the
      difference between PaCO2 and PETCO2 (P(a-ET)CO2) has therapeutic implications.
      The P(a-ET)CO2 was hypothesized to be stable during craniotomies with relatively
      short-term monitoring and controlled cardiorespiratory variables. Thirty-five
      patients undergoing elective craniotomies were studied. Arterial blood gases
      (with PaCO2) were measured after induction of general anesthesia, after cranium
      opening prior to dural incision, and at start of closure; PETCO2 was
      simultaneously determined with infrared capnometry. The PaCO2 was 31.9 +/- 3.9 mm
      Hg (range, 24.8-46.7) (values are mean +/- SD) and PETCO2, 24.7 +/- 3.8 mm Hg
      (range, 16-34), with a P(a-ET)CO2 of 7.2 +/- 3.3 mm Hg (of 126 comparisons, range
      was -1.2-17.3). There was no correlation of P(a-ET)CO2 with blood pressure, heart
      rate, respiratory volumes, airway pressures, or inspired oxygen concentration.
      There was a significant positive correlation between PaCO2 and PETCO2 (r = 0.632,
      slope = 0.609) and P(a-ET)CO2 and PaCO2 (r = 0.46, slope = 0.391, P < 0.017, and
      r2 = 0.22). Although changes in the study population of PaCO2 and PETCO2
      correlated statistically (r = 0.818, slope = 0.76, P < 0.001, r2 = 0.669),
      comparisons in 17 of 35 individuals were not significant. On comparison of
      subsequent measurements, 18.4% of changes in PaCO2 and PETCO2 (although sometimes
      small) were in opposite directions. P(a-ET)CO2 did not change with time. The
      PETCO2 does not provide a stable reflection of PaCO2 in many patients undergoing
      craniotomies.

PMID- 7574015
TI  - Comparison of isoflurane and desflurane anesthetic depth using burst suppression
      of the electroencephalogram in neurosurgical patients.
AB  - We compared the anesthetic effects of desflurane and isoflurane using percent
      burst suppression of the electroencephalogram (EEG) as an end-point in 10
      neurosurgical patients. The EEG was recorded from frontal leads and processed
      variables were analyzed as a function of increasing isoflurane and desflurane
      concentration with age and baseline delta EEG power (0.5-3.75 Hz) as independent
      variables. Isoflurane and desflurane (0.5, 1.0, 1.5, 2.0 minimum alveolar
      anesthetic concentration [MAC]) were incrementally administered until the EEG was
      quiesecent at least 40% of the time. Both anesthetics were evaluated separately
      in each patient. By analysis of variance, isoflurane and desflurane produced dose
      related increments in burst suppression which were significantly affected by the
      age and baseline delta EEG of the patient. When isoflurane and desflurane were
      equated by MAC and adjusted for age, they produced statistically similar patterns
      of EEG burst suppression. Within subjects, a high degree of correlation was
      observed for percent burst suppression between equipotent levels of isoflurane
      and desflurane (r = 0.85; P < 0.05). Patients with baseline delta EEG power less
      than 80% of total power showed increases in delta EEG and decreases in median
      frequency with isoflurane and desflurane. Patients with baseline delta EEG power
      > 80% of total power produced no change in EEG frequency with increasing
      anesthesia but revealed a greater sensitivity to the development of burst
      suppression. These results show that isoflurane and desflurane produce similar
      EEG suppression in neurosurgical patients. If the EEG is initially slow, further
      slowing cannot be used to assess anesthetic depth.

PMID- 7574016
TI  - The effects of anesthesia with increasing end-expiratory concentrations of
      sevoflurane on midlatency auditory evoked potentials.
AB  - We studied midlatency auditory evoked potentials (MLAEP) during general
      anesthesia with increasing end-expiratory concentrations of sevoflurane in 12
      patients scheduled for elective gynecologic surgery. After oral premedication
      with 20 mg clorazepate dipotassium, anesthesia was induced with etomidate (0.2
      mg/kg intravenously [IV]). Vecuronium (0.1 mg/kg) was given for neuromuscular
      block, and controlled ventilation with sevoflurane in 100% O2 was instituted.
      Auditory evoked potentials were recorded in the awake state and during anesthesia
      with end-expiratory steady-state concentrations of 0.5, 1.0, 1.5, and 2.0 vol% of
      sevoflurane on vertex (positive) and mastoids on both sides (negative). Latencies
      of peaks V, Na, Pa, Nb, and P1 (ms) and amplitudes of Na/Pa, Pa/Nb, and Nb/P1
      (microV) were measured. In the awake state, MLAEP had high peak-to-peak
      amplitudes and a periodic waveform. During general anesthesia with increasing end
      expiratory concentrations of sevoflurane, the latency of the brainstem response V
      increased slightly. In contrast, MLAEP showed marked dose-dependent,
      statistically significant increases in the latencies of Na, Pa, Nb, and P1 and
      decreases in the amplitudes of Na/Pa, Pa/Nb, and Nb/P1. Under 2 vol% of
      sevoflurane, MLAEPs were severely attenuated or abolished. Based on these
      observations, > or = 1.5 vol% sevoflurane should suppress phenomena such as
      auditory perceptions, intraoperative wakefulness, and awareness.

PMID- 7574017
TI  - Sevoflurane for outpatient anesthesia: a comparison with propofol.
AB  - Three different anesthetic techniques were compared in 146 healthy outpatients
      undergoing ambulatory surgery. In Groups I and II, anesthesia was induced with
      propofol (1.5-2.0 mg/kg, intravenously [iv]) and maintained with nitrous oxide
      (N2O) 60% in oxygen and either a propofol infusion, 75-160 micrograms.kg-1.min-1
      IV, or sevoflurane, 1%-2% end-tidal, respectively. In Group III, anesthesia was
      induced and maintained with sevoflurane, 1%-4% end-tidal and N2O 60% in oxygen.
      In addition to 60% N2O in oxygen at a total gas flow of 3 L/min, all patients
      received fentanyl, 2-3 micrograms/kg IV, and vecuronium, 0.1 mg/kg IV. IV
      induction of anesthesia with propofol (90 +/- 53 s and 94 +/- 48 s in Groups I
      and II, respectively) was significantly faster than inhalation induction with
      sevoflurane (153 +/- 100 s). There were no significant differences in the
      incidence of coughing, airway irritation, or laryngospasm during induction of
      anesthesia. Although the mean arterial blood pressure values were similar in all
      three groups, the use of sevoflurane was associated with consistently lower heart
      rate values during the early maintenance period. Early and intermediate recovery
      times were the same in all three treatment groups. The use of sevoflurane for
      induction and/or maintenance of anesthesia was associated with a higher incidence
      of postoperative emetic sequelae compared with propofol. Finally, the times at
      which patients were considered "fit for discharge" and the actual discharge times
      were similar in all three groups. Sevoflurane is an acceptable alternative to
      propofol for induction and maintenance of outpatient anesthesia.

PMID- 7574018
TI  - Maternal and neonatal fentanyl and bupivacaine concentrations after epidural
      infusion during labor.
AB  - Labor analgesia using continuous epidural infusions of low-dose bupivacaine and
      fentanyl may be maintained for many hours. We examined the potential for drug
      accumulation in both mother and neonate after these long-term infusions. Pregnant
      women receiving a 10-mL/h continuous infusion of labor analgesia with 0.125%
      bupivacaine and 2 micrograms/mL of fentanyl were evaluated. Maternal venous and
      umbilical venous drug concentrations were measured at delivery. Umbilical artery
      blood gases were obtained. Scanlon neurobehavioral testing was performed on all
      infants. Length of infusion times varied from 1 to 15 h. Maternal and neonatal
      drug concentrations remained relatively constant throughout the infusion period.
      All umbilical blood gas values and neurobehavioral scores were within normal
      limits. In conclusion, even when maintained for many hours, continuous infusion
      labor analgesia does not appear to result in significant fetal drug accumulation.
      No adverse neonatal effects were seen.

PMID- 7574019
TI  - Determination of the minimum local analgesic concentrations of epidural
      bupivacaine and lidocaine in labor.
AB  - The aim of this study was to devise a clinical model to determine the effective
      concentrations in 50% of patients (EC50) for bupivacaine and lidocaine in the
      first stage of labor and define EC50 as the minimum local analgesic concentration
      (MLAC). This should allow the determination of relative analgesic potency and,
      subsequently, the local anesthetic sparing efficacy of other epidural analgesics.
      Parturients not exceeding 5 cm cervical dilation who requested epidural analgesia
      were enrolled. The two studies involved 81 women (bupivacaine n = 41, lidocaine n
      = 40). After a lumbar epidural catheter was placed, 20 mL of the concentration of
      local anesthetic being tested was given. The concentration was determined by the
      response of the previous patient to a higher or lower concentration using double
      blinded, up-down sequential allocation. Efficacy was assessed using 100-mm visual
      analog pain scores with less than 10 mm within 1 h defined as effective. MLAC was
      determined using the formula of Dixon and Massey. Results show MLAC bupivacaine
      0.065% (95% confidence interval [CI] 0.045-0.085), MLAC lidocaine 0.37% (95% CI
      0.32-0.42), equivalent to 2 and 14 mmol solutions, respectively. Thus bupivacaine
      was 5.7 times more potent than lidocaine in weighted and 7 times more potent in
      molar ratios at analgesic EC50, in the volume of local anesthetic studied.

PMID- 7574020
TI  - Prevention of hypotension after spinal anesthesia for cesarean section: six
      percent hetastarch versus lactated Ringer's solution.
AB  - This study was designed to determine whether preoperative administration of 6%
      hetastarch decreases the incidence and severity of hypotension after spinal
      anesthesia for cesarean section. Forty nonlaboring ASA class I and II women
      having nonurgent cesarean sections were randomized to receive either 500 mL of 6%
      hetastarch plus 1 L lactated Ringer's solution (LR) (n = 20), or 2 L of LR (n =
      20) prior to induction of spinal anesthesia. Hypotension occurred in 45% of
      patients who received hetastarch vs 85% of those who received only LR (P < 0.05),
      and minimum systolic blood pressure was lower in the LR group than in the
      hetastarch group (85 +/- 12 vs 93 +/- 12 mm Hg [mean +/- SD]; P < 0.05). In
      addition, the LR group had a higher maximum heart rate (115 +/- 17 vs 104 +/- 16
      bpm), a shorter mean time to hypotension (7 +/- 4 vs 10 +/- 7 min), and required
      more 5-mg doses of ephedrine for treatment of hypotension (0 vs 2 [median]; P <
      0.05) than the hetastarch group. Neonatal outcome, as determined by Apgar scores
      and cord blood gas analyses, was good and similar in both groups. We conclude
      that 6% hetastarch plus LR is more effective than LR alone and that its routine
      use before spinal anesthesia for cesarean section should be considered.

PMID- 7574021
TI  - Cardiovascular responses to noxious stimuli during isoflurane anesthesia are
      minimally affected by anesthetic action in the brain.
AB  - We investigated the ability of isoflurane to ablate cardiovascular responses to a
      noxious stimulus (dew-claw clamp) in 10 goats during isoflurane delivery
      throughout the body and with selective delivery to either the head or torso.
      Whole-body minimum alveolar anesthetic concentration (MAC) and the concentration
      blocking autonomic responses (MAC-BAR) were determined. Next, cranial blood
      (jugular vein) was drained into an oxygenator and reinfused into the head
      (carotid artery). In six animals (Group I) isoflurane to the torso was maintained
      at 0.2%-0.3%, and the cranial isoflurane concentration adjusted to determined MAC
      BAR; in three animals (Group II) cranial isoflurane was maintained at 0.2%-0.3%,
      and the end-tidal isoflurane adjusted to determine MAC-BAR. Whole-body MAC was
      1.4% +/- 0.3%; whole-body MAC-BAR was 3.7% +/- 0.4%, a concentration range
      associated with hypotension (46 +/- 8 mm Hg). During bypass, MAC-BAR was 5.6% +/-
      2.4% for Group I (P < 0.05) and 2.2% +/- 0.7% for Group II (P < 0.05). Changes in
      blood pressure, but not heart rate, correlated with the isoflurane concentration,
      both during the whole-body period and bypass period for Groups I and II. We
      conclude that isoflurane suppresses the arterial blood pressure response to
      noxious stimuli, but only with concomitant hypotension, and that the brain has
      little influence on this response, as its MAC-BAR substantially exceeded whole
      body MAC-BAR.

PMID- 7574022
TI  - Ketamine, at clinical concentrations, does not alter the function of cardiac
      sarcoplasmic reticulum calcium release channels.
AB  - In the absence of sympathetically mediated stimulation, ketamine depresses
      myocardial contractility. This results from a decrease in the availability of
      intracellular Ca2+ for excitation-contraction coupling. Although sites of action
      other than the Ca2+ release channel of sarcoplasmic reticulum have been
      implicated, ketamine-induced alterations in Ca2+ efflux from the sarcoplasmic
      reticulum remain contentious. The purpose of the present study was to identify
      interactions of ketamine with the calcium release channel using sarcoplasmic
      reticulum enriched vesicles from porcine left ventricle. Ketamine did not alter
      [3H]ryanodine binding at concentrations of 1 mM or less, while binding was almost
      completely inhibited at 10 mM. Gating and conductance of SR Ca2+ channels studied
      in planar bilayers was not altered by clinical concentrations of ketamine over
      the range of physiologic cytoplasmic free Ca2+ concentrations. Channel
      inactivation was observed at 10 mM ketamine, well in excess of clinical
      concentrations. These findings indicate that clinical concentrations of ketamine
      do not alter the function of the Ca2+ release channel. Alterations in
      intracellular Ca2+ homeostasis that result in depression of myocardial
      contractility must therefore result from effects at other sites along the
      excitation-contraction coupling pathway.

PMID- 7574023
TI  - Glucuronidation of propofol in microsomal fractions from various tissues and
      species including humans: effect of different drugs.
AB  - This in vitro study was conducted to evaluate propofol glucuronidation and the
      effect of concomitantly administered drugs in various species. Propofol
      glucuronidation was studied in microsomal fractions from rat, rabbit, and human
      livers. Extrahepatic metabolism was investigated using lung and kidney
      microsomes. The propofol-uridine diphosphate-glucuronosyltransferase (UGT)
      activity measured in liver microsomes was higher in rabbit than in rat. Among the
      three tested species, human livers exhibited the highest activity, with only
      small variability in the three samples studied. Animal kidney, but not lung
      (animal or human), microsomes were able to glucuronidate propofol, meaning that
      extrahepatic metabolism of propofol exists, at least in the kidney, in the tested
      species (rat and rabbit). Since metabolic interactions are potential sources of
      prolonged drug effect or overdose, we screened the effect of 21 compounds (known
      substrates of various UGT or potentially coadministered drugs) on the
      glucuronidation of propofol by human liver microsomes. Inhibitions obtained with
      chemicals or drugs glucuronidated by either UGT1 or UGT2 families (1-naphtol, 4
      hydroxybiphenyl, carvacrol, n-propylgallate, ketoprofen, chloramphenicol,
      acetylsalicylic acid) indicated that at least two UGT isoforms are involved in
      propofol glucuronidation. Inhibition was observed with several drugs potentially
      coadministered during pre-, per, or postoperative periods (e.g., acetylsalicyclic
      acid, ketoprofen, oxazepam, fentanyl). Although not directly transposable to the
      in vivo situation, these results indicate that such interactions are
      theoretically possible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574027
TI  - The Bullard laryngoscope for emergency airway management in a morbidly obese
      parturient.

PMID- 7574026
TI  - Mandibular tori as a cause of inability to visualize the larynx.

PMID- 7574025
TI  - Is it time to reevaluate the airway management of tracheoesophageal fistula?

PMID- 7574028
TI  - Opiates in ethanol withdrawal.

PMID- 7574024
TI  - Chronic treatment with nitric oxide synthase (NOS) inhibitor profoundly reduces
      cerebellar NOS activity and cyclic guanosine monophosphate but does not modify
      minimum alveolar anesthetic concentration.
AB  - We previously found that acute administration of a nitric oxide synthase (NOS)
      inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) does not reduce the
      minimum alveolar anesthetic concentration (MAC) of halothane in rats. However, a
      recent study has suggested that brain NOS activity could not be inhibited by more
      than approximately 50% by acute administration of L-NAME. To investigate the
      effect of marked inhibition of NOS activity on the MAC of halothane, we measured
      cerebellar NOS activity, cerebellar cyclic guanosine monophosphate (cGMP) levels,
      and halothane MAC in rats chronically treated with L-NAME and compared the
      results to those of the saline-treated control group. Although the cerebellar NOS
      activity and cGMP levels were significantly decreased (14% and 2.7% of control,
      respectively) by L-NAME, the value of the halothane MAC was not significantly
      affected. These results suggest that the anesthetic action of halothane, as
      measured by its MAC in rats, is not related to NOS activity or cGMP levels in the
      brain.

PMID- 7574029
TI  - Anaphylactoid reaction in a surgeon to surgical rubber gloves.

PMID- 7574030
TI  - Transient blindness during hysteroscopy: a rare complication.

PMID- 7574031
TI  - Ultrasonographic guidance in placing a catheter for continuous axillary brachial
      plexus block.

PMID- 7574032
TI  - Succinylcholine: changes in labeling.

PMID- 7574033
TI  - How deep may we insert the cannulation needle for catheterization of the internal
      jugular vein in pediatric patients undergoing cardiovascular surgery?

PMID- 7574034
TI  - Acrylic nails and pulse oximemtry.

PMID- 7574035
TI  - Cerebrospinal fluid leakage, spinal needles, and postdural puncture headache
      (PDPH)

PMID- 7574036
TI  - Ethanol monitoring of fluid absorption: education is important.

PMID- 7574037
TI  - The publication of commercially supported supplements statement.

PMID- 7574038
TI  - The publication of commercially supported supplements statement.

PMID- 7574040
TI  - Left ventricular ejection time and end-systolic pressure revisited.

PMID- 7574041
TI  - Oxygen is cost effective.

PMID- 7574039
TI  - The publication of commercially supported supplements statement.

PMID- 7574044
TI  - Effects of acadesine on the incidence of myocardial infarction and adverse
      cardiac outcomes after coronary artery bypass graft surgery. Multicenter Study of
      Perioperative Ischemia (McSPI) Research Group.
AB  - BACKGROUND: Acadesine (AICA riboside) (5-amino-1-[beta-D-ribofuranosyl]imidazole
      4-carboxamide) is a purine nucleoside analog belonging to a new class of agents
      generally termed adenosine regulating agents (ARAs) that increase the
      availability of adenosine locally in ischemic tissues. The effects of acadesine
      on the incidence of fatal and nonfatal myocardial infarction (MI) an on the
      incidence of all adverse cardiovascular outcomes (cardiac death, MI, congestive
      heart failure, life-threatening dysrhythmia, or cerebrovascular accident) was
      investigated in patients undergoing coronary artery bypass graft (CABG) surgery.
      METHODS: In 20 medical centers in the United States participating in the
      Multicenter Study of Perioperative Ischemia (McSPI), 633 patients undergoing CABG
      surgery were randomized in a double-blind fashion to receive either placebo (n =
      212), low-dose acadesine (0.05 mg.kg-1.min-1, n = 214), or high-dose acadesine
      (0.1 mg.kg-1.min-1, n = 207) by intravenous infusion starting 15 min before
      anesthetic induction and continuing for 7 h, as well as added to the cardioplegic
      solution (final concentration of 5 micrograms/ml for those patients receiving
      acadesine). Anesthesia was standardized, and perioperative hemodynamics were to
      be strictly controlled. Twelve-lead electrocardiograms (ECGs), CK-MB isoenzyme
      concentrations, and autopsy were used to assess the occurrence of MI. RESULTS:
      There was a similar incidence of adverse events in the acadesine groups and the
      placebo group, with the exception that serum uric acid transiently increased in
      the high-dose acadesine group. The incidence of perioperative MI, using the
      prespecified MI criterion (EGF Q wave, CK-MB elevation, or autopsy evidence), was
      not different between groups (24% versus 26% versus 21% [P = 0.574]), nor was the
      incidence of all cardiovascular outcomes (30% versus 30% versus 22% [P = 0.151]).
      After completion of the study, a post hoc analysis also was performed using the
      more specific definition of MI (ECG Q wave and CK-MB elevation, or autopsy
      evidence), and the incidence of MI was lower (P = 0.018, alpha = 0.017, corrected
      for multiple comparisons), as were adverse cardiovascular outcomes (P = 0.002)
      and CVA (P = 0.02) for patients treated with 0.1 mg.kg-1.min-1 acadesine. In
      patients with Q-wave infarction, the high-dose acadesine group had a lower peak
      median CK-MB (P = 0.042) and area under the CK-MB curve (P = 0.021). No
      differences were found in the incidence or characteristics of MI (Holter or
      transesophageal echocardiography). CONCLUSIONS: The results of this trial did not
      demonstrate a statistically significant difference between acadesine and placebo
      using the prespecified criterion for MI. Of interest are the results of the post
      hoc analysis, using the more specific criterion for MI, which indicate that
      acadesine may reduce the incidence of larger Q-wave infarctions after coronary
      artery bypass surgery. A second trial is underway to evaluate this contention.

PMID- 7574042
TI  - A nuclear magnetic resonance advance. Imaging fluorinated anesthetics in the
      brain.

PMID- 7574045
TI  - Spontaneous ventilation with halothane in children. A comparative study between
      endotracheal tube and laryngeal mask airway.
AB  - BACKGROUND: It has been reported that, in children breathing spontaneously via an
      endotracheal tube, halothane depresses ventilation with paradoxic inspiratory
      movement. Endotracheal tubes have a higher airflow resistance than do laryngeal
      mask airways (LMAs). Therefore, the aim of this study was to compare spontaneous
      ventilation via the LMA with that via the endotracheal tube in children
      anesthetized with halothane. METHODS: The authors studied two groups of 6-24
      month-old children with no cardiorespiratory and neurologic disorders, undergoing
      elective minor surgery with halothane anesthesia: one group breathing via LMA (n
      = 10) and one group breathing via endotracheal tube (n = 10). They measured tidal
      volume, respiratory rate, minute ventilation, and end-tidal CO2. They assessed
      paradoxic inspiratory movement using amplitude index and phase delay index.
      RESULTS: Age and weight were similar in both groups. Mean +/- SD tidal volume
      (7.5 +/- 1.9 ml/kg in the LMA group vs. 5.3 +/- 1.1 ml/kg in the endotracheal
      tube group; P < 0.05) and minute ventilation (325 +/- 105 ml.min-1.kg-1 in the
      LMA group vs. 246 +/- 38 ml.min-1.kg-1 in the endotracheal tube group; P < 0.05)
      were lower in the endotracheal tube group. The phase delay index (18 +/- 11% in
      the LMA group vs. 41 +/- 19% in the endotracheal tube group; P < 0.05) and the
      amplitude index (25 +/- 43% in the LMA group vs. 74 +/- 72% in the endotracheal
      tube group; P < 0.05) were significantly smaller with the LMA than with the
      endotracheal tube. CONCLUSIONS: In 6-24-month-old children anesthetized with
      halothane, paradoxic inspiratory movement is less when breathing through an LMA
      than through an endotracheal tube.

PMID- 7574046
TI  - Influence of high-dose aprotinin on anticoagulation, heparin requirement, and
      celite- and kaolin-activated clotting time in heparin-pretreated patients
      undergoing open-heart surgery. A double-blind, placebo-controlled study.
AB  - BACKGROUND: Aprotinin causes a prolongation of the celite-activated clotting time
      (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern
      has been raised regarding the reliability of CACT to monitor anticoagulation in
      the presence of aprotinin. The current study was designed to test the efficacy of
      aprotinin to improve anticoagulation, and to investigate whether the prolongation
      of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate
      this antithrombotic effect of aprotinin, this study was done in patients prone to
      reduced intraoperative heparin sensitivity. METHODS: In a prospective,
      randomized, double-blind clinical trial, 30 male patients scheduled for elective
      primary coronary revascularization and treated with heparin for at least 10 days
      preoperatively, received either high-dose aprotinin (group A) or placebo (group
      C). The CACT and KACT were determined, but only CACT was used to control
      anticoagulation with heparin. Parameters of coagulation that are indicators of
      thrombin generation and activity (F1+2 prothrombin fragments, thrombin
      antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D
      dimers), aprotinin, and heparin plasma concentrations were measured.
      Postoperative blood loss and allogeneic blood transfused were recorded. RESULTS:
      Total heparin administered was 36,200 units (95% confidence interval: 31,400
      41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05).
      Hemostatic activation during cardiopulmonary bypass (CPB) was significantly
      reduced in group A compared with group C. After 60 min of CPB, all parameters
      were significantly different (P < 0.05) between the groups (group C vs. group A):
      F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml;
      thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38)
      ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis
      was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and
      2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5
      min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C
      and A, respectively (P < 0.05), whereas the KACT showed no differences between
      the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P
      = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for
      groups C and A, respectively (P < 0.05). CONCLUSIONS: Aprotinin treatment in
      combination with heparin leads to less thrombin generation during CPB. Aprotinin
      has anticoagulant properties. Celite-activated ACT is reliable for monitoring
      anticoagulation in the presence of aprotinin, because the prolonged CACT in the
      aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not
      reflect this effect of aprotinin.

PMID- 7574047
TI  - Preoperative pregnancy testing in ambulatory surgery. Incidence and impact of
      positive results.
AB  - BACKGROUND: The incidence of unrecognized early pregnancy and its influence on
      the surgical and anesthetic course in patients presenting for elective ambulatory
      surgery have not been previously determined. The current study was designed to
      determine the incidence of unrecognized pregnancy in women presenting for
      ambulatory surgery. In addition, it examined how discovery of the pregnancy
      altered the anesthetic or surgical course. METHODS: In a prospective study over a
      1-yr period, all women of childbearing potential (defined as menstruating women
      without prior hysterectomy or tubal ligation) were preoperatively evaluated and
      tested for urine or serum human chorionic gonadotropin, to determine unrecognized
      pregnancy. If a pregnancy was detected, the disposition of the surgical procedure
      and the effect on the surgical and anesthetic management was recorded. RESULTS:
      Of 2,056 women of childbearing potential presenting for ambulatory surgery,
      testing revealed 7 previously unrecognized pregnancies, an incidence of 0.3%.
      Included among these patients were two patients scheduled to undergo fertility
      procedures. On learning the test result and even before being advised of
      available options, all patients elected to cancel or postpone the surgical
      procedure. CONCLUSIONS: The incidence of previously unrecognized pregnancy in
      menstruating women presenting for ambulatory, nonobstetric surgery was 0.3%. The
      knowledge of a positive test resulted in cancellation or postponement of the
      operative procedure. Patient desire for cancellation was the main determining
      factor in each case.

PMID- 7574043
TI  - Protracted relief of experimental neuropathic pain by systemic local anesthetics.
      How, where, and when.

PMID- 7574048
TI  - Enzymatic antagonism of mivacurium-induced neuromuscular blockade by human plasma
      cholinesterase.
AB  - BACKGROUND: Mivacurium chloride is a bis-benzylisoquinolinium nondepolarizing
      neuromuscular blocking agent, hydrolyzed by butyrylcholinesterase (PCHE). The
      dose-response relationships for PCHE after mivacurium have not been studied.
      Therefore, this study was designed to establish dose-response relationships for
      PCHE as an antagonist of mivacurium-induced neuromuscular blockade. METHODS:
      Forty-eight physical status 1 adults were given 0.15 mg/kg mivacurium during
      fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Train-of-four (TOF)
      stimulation was applied to the ulnar nerve every 12 s, and the force of
      contraction of the adductor pollicis muscle was recorded. When spontaneous
      recovery of first twitch height (T1) reached 10% of its initial control value,
      exogenous PCHE equivalent to activity present in 2.5, 5, 7.5, 15, or 25 ml/kg of
      human plasma was administered by random allocation to 40 patients. Neuromuscular
      function in another eight subjects was allowed to recover spontaneously. Two
      blood samples were taken for determination of plasma cholinesterase activity. The
      first sample was taken before induction of anesthesia, and the second sample was
      taken when the TOF ratio had recovered to 0.75. Dibucaine and fluoride numbers
      were determined from the first assay. RESULTS: Administration of PCHE produced
      significant increases in PCHE activity in all patients. The larger the dose, the
      greater was the resultant plasma activity. Human PCHE produced a dose-dependent
      antagonism of mivacurium-induced neuromuscular blockade and the recovery times
      correlated inversely with PCHE activity (P < 0.01). The recovery of T1 was
      greater (P < 0.01) and time to attain a TOF ratio of 0.75 was shorter (P < 0.01)
      with any dose of PCHE than that observed in the spontaneous recovery group. After
      the administration of exogenous PCHE equivalent to activity present in 25 ml/kg
      of human plasma, recovery of TOF ratio to 0.75 or more was observed in all
      patients in less than 10 min and time to attain a TOF ratio of 0.75 was 55%
      shorter than the spontaneous recovery group (8.4 [7.1-9.7] vs. 18.7 [15.4-22]
      min; mean and 95% confidence intervals). CONCLUSIONS: Administration of exogenous
      PCHE equivalent to activity present in 25 ml/kg of human plasma (in a 65-kg
      patient, this dose is equivalent to PCHE activity of 1,625 ml of adult human
      plasma) resulted in reliable antagonism of mivacurium-induced neuromuscular
      blockade. Nevertheless, because of the prohibitive cost of this compound, this
      reversal modality is unlikely to have a routine practical application at this
      time.

PMID- 7574049
TI  - Pulse width, stimulus intensity, electrode placement, and polarity during
      assessment of neuromuscular block.
AB  - BACKGROUND: Although the intensity of neurostimulation (i.e., charge) is a
      product of current intensity and pulse duration, the effects of the latter on the
      amplitude of evoked response and subjective discomfort are unknown. Therefore,
      the authors investigated the effects of current intensity and pulse width, and
      their interaction with electrode placement and polarity, on force translation
      (FTR), accelerography (ACG), and electromyography (EMG) at the adductor pollics
      muscle. METHODS: Ulnar stimulating electrodes were applied in one of two
      configurations: over the distal forearm and olecranon groove ("A") or 5 cm apart
      on the distal forearm ("B"). Stimuli for FTR and EMG with current intensities of
      20, 40, 60, and 70 mA and pulse widths of 0.05, 0.1, 0.2, and 0.4 msec resulted
      in 16 different charges. These combinations were delivered in each of four
      orientations: "A-" ("A" configuration with negative electrode distal); "A+", "B
      ", and "B+" (n = 64 stimuli). Eight stimulus combinations (n = 32 stimuli) were
      used for ACG. For each monitoring technique, the effects of current intensity,
      pulse width, electrode polarity, and placement were analyzed with repeated
      measures ANOVA. Pain responses were scored on a 0-100-mm verbal analog scale and
      analyzed with ANOVA and Fisher's exact test. RESULTS: The evoked response
      amplitude varied directly with current intensity and pulse width. In both
      electrode placement configurations, the response was greater when the negative
      electrode was distal. The electrode positioning ("A" vs. "B") had less of an
      impact on evoked responses than did polarity, regardless of monitoring technique.
      The evoked pain varied directly with the amplitude of evoked neuromuscular
      response in all electrode position-polarity combinations. CONCLUSIONS: The total
      current charge required for evoking a supramaximal neuromuscular response is much
      higher than previously appreciated, and electrode polarity is important in
      attaining a supramaximal plateau. Failure to attain (and maintain) a supramaximal
      stimulus allows changes in the effectiveness of neurostimulation, thus
      influencing the magnitude of the evoked neuromuscular response and confounding
      measurements of neuromuscular block.

PMID- 7574050
TI  - Cardiorespiratory effects of positive end-expiratory pressure during progressive
      tidal volume reduction (permissive hypercapnia) in patients with acute
      respiratory distress syndrome.
AB  - BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the
      ventilatory approach is based on tidal volume (VT) of 10-15 ml/kg and positive
      end-expiratory pressure (PEEP). To avoid further pulmonary injury, decreasing VT
      and allowing PaCO2 to increase (permissive hypercapnia) has been suggested.
      Effects of 10 cmH2O of PEEP on respiratory mechanics, hemodynamics, and gas
      exchange were compared during mechanical ventilation with conventional (10-15
      ml/kg) and low (5-8 ml/kg) VT. METHODS: Nine sedated and paralyzed patients were
      studied. VT was decreased gradually (50 ml every 20-30 min). Static volume
      pressure (V-P) curves, hemodynamics, and gas exchange were measured. RESULTS:
      During mechanical ventilation with conventional VT, V-P curves on PEEP 0 (ZEEP)
      exhibited an upward convexity in six patients reflecting a progressive reduction
      in compliance with inflating volume, whereas PEEP resulted in a volume
      displacement along the flat part of this curve. After VT reduction, V-P curves in
      the same patients showed an upward concavity, reflecting progressive alveolar
      recruitment with inflating volume, and application of PEEP resulted in alveolar
      recruitment. The other three patients showed a V-P curve with an upward
      concavity; VT reduction increased this concavity, and application of PEEP induced
      greater alveolar recruitment than during conventional VT. With PEEP, cardiac
      index decreased by, respectively, 31% during conventional VT and 11% during low
      VT (P < 0.01); PaO2 increased by 32% and 71% (P < 0.01), respectively, whereas
      right-to-left venous admixture (Qs/Qt) decreased by 11% and 40%, respectively (P
      < 0.01). The greatest values of PaO2, static compliance, and oxygen delivery and
      the lowest values of Qs/Qt (best PEEP) were obtained during application of PEEP
      with low VT (P < 0.01). CONCLUSIONS: Although PEEP induced alveolar
      hyperinflation in most patients during mechanical ventilation with conventional
      VT, at low VT, there appeared to be a significant alveolar collapse, and PEEP was
      able to expand these units, improving gas exchange and hemodynamics.

PMID- 7574051
TI  - Effects of sufentanil on cerebral hemodynamics and intracranial pressure in
      patients with brain injury.
AB  - BACKGROUND: The current study investigates the effects of sufentanil on cerebral
      blood flow velocity and intracranial pressure (ICP) in 30 patients with
      intracranial hypertension after severe brain trauma (Glasgow coma scale < 6).
      METHODS: Mechanical ventilation (FIO2 0.25-0.4) was adjusted to maintain arterial
      carbon dioxide tensions of 28-30 mmHg. Continuous infusion of midazolam (200
      micrograms/kg/h intravenous) and fentanyl (2 micrograms/kg/h intravenous) was
      used for sedation. Mean arterial blood pressure (MAP, mmHg) was adjusted using
      norepinephrine infusion (1-5 micrograms/min). Mean blood flow velocity (Vmean,
      cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial
      Doppler sonography system. ICP (mmHg) was measured using an epidural probe. After
      baseline measurements, a bolus of 3 micrograms/kg sufentanil was injected, and
      all parameters were continuously recorded for 30 min. The patients were assigned
      retrospectively to the following groups according to their blood pressure
      responses to sufentanil: group 1, MAP decrease of less than 10 mmHg, and group 2,
      MAP decrease of more than 10 mmHg. RESULTS: Heart rate, arterial blood gases, and
      esophageal temperature did not change over time in all patients. In 18 patients,
      MAP did not decrease after sufentanil (group 1). In 12 patients, sufentanil
      decreased MAP > 10 mmHg from baseline despite norepinephrine infusion (group 2).
      ICP was constant in patients with maintained MAP (group 1) but was significantly
      increased in patients with decreased MAP. Vmean did not change with sufentanil
      injection regardless of changes in MAP. CONCLUSIONS: The current data show that
      sufentanil (3 micrograms/kg intravenous) has no significant effect on middle
      cerebral artery blood flow velocity and ICP in patients with brain injury,
      intracranial hypertension, and controlled MAP. However, transient increases in
      ICP without changes in middle cerebral artery blood flow velocity may occur
      concomitant with decreases in MAP. This suggests that increases in ICP seen with
      sufentanil may be due to autoregulatory decreases in cerebral vascular resistance
      secondary to systemic hypotension.

PMID- 7574052
TI  - Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A
      prospective analysis of 1,014 patients.
AB  - BACKGROUND: Epidural fentanyl/bupivacaine infusions often are limited to high
      dependency units or intensive care units. One thousand fourteen patients
      receiving epidural fentanyl/bupivacaine infusions for analgesia after major
      surgery who were managed in the general surgical ward were prospectively
      surveyed. METHODS: Patients leaving the recovery room with an epidural catheter
      in situ were assessed three times a day by acute pain service personnel for
      quality of pain relief, using a rating scale that accounted for pain on movement.
      The presence of side effects and complications was assessed. RESULTS: Data were
      collected from February 1990 to May 1993. The average duration of infusion was 3
      days. A patient's pain relief was rated as good to excellent on 82.6% of visits.
      Side effects possibly attributable to fentanyl included sedation (7.4%), pruritus
      (10.2%), nausea and vomiting (3.1%), and respiratory depression (1.2%).
      Respiratory depression commonly was associated with sedation and was detected
      easily on the postsurgical ward, with only four patients requiring naloxone
      (0.4%). Side effects possibly related to bupivacaine included unpleasant sensory
      block (2.6%), significant lower limb motor block (3.0%), and hypotension (6.6%).
      There were two cases of epidural hematoma. Inflammation at the epidural catheter
      insertion site occurred in 3.8% (38), of which 42% (16) had some cutaneous
      purulence detected. There were no epidural space infections. Mechanical problems,
      including dislodgment of the catheter, accounted for 18.7% of infusion
      discontinuations within the first 72 h. CONCLUSIONS: Postoperative epidural
      fentanyl/bupivacaine infusions are effective and can be managed readily in
      general postsurgical wards with minimal complications provided that appropriate
      patient observations are performed.

PMID- 7574053
TI  - Near-infrared measurement of cerebral oxygenation. Correlation with
      electroencephalographic ischemia during ventricular fibrillation.
AB  - BACKGROUND: The application of phase-modulated near-infrared techniques for
      measurement of the oxygen saturation of cerebral tissue requires both validation
      by conventional measures of cerebral oxygenation and determination of normal and
      abnormal values. This study was undertaken to validate phase-modulated near
      infrared measurements of cerebral oxygen saturation by comparing them with
      electroencephalographic evidence of cerebral ischemia during implantation of
      cardioverting defibrillators. This comparison also yields an estimate of the
      ischemic threshold as measured with near-infrared techniques. METHODS:
      Electroencephalograms and near-infrared measurements were performed during 85
      episodes of ventricular fibrillation in ten patients. Light at 754, 785, and 816
      nm was modulated at 200 MHz, transmitted through the skull, and the path lengths
      of the reflected light were determined by measuring the phase shifts. The
      electroencephalogram was inspected for changes during the hypotension associated
      with the arrhythmia and the oxygen saturation was calculated from the near
      infrared path lengths. Changes in oxygen saturation were then compared with
      electroencephalographic evidence of cerebral ischemia. RESULTS: The mean
      saturation before fibrillation was 56.5% +/- 1.2 (SEM). In 40 (47%) of the
      events, electroencephalographic evidence of ischemia was observed. Such changes
      were related to the minimum saturation observed during ventricular fibrillation
      (44% +/- 2.5 vs. 56% +/- 1.9 in the absence of electroencephalographic changes; P
      < 0.001). The ischemic threshold was estimated to be 47% saturation. The
      sensitivity of this technique was estimated to be 0.6, the specificity 0.84, and
      the predictive accuracy 0.73. CONCLUSIONS: Near-infrared measurements reflect
      changes in cerebral oxygenation as indicated by electroencephalographic evidence
      of cerebral ischemia.

PMID- 7574054
TI  - Validation of the alfentanil canonical univariate parameter as a measure of
      opioid effect on the electroencephalogram.
AB  - BACKGROUND: Several parameters derived from the multivariate
      electroencephalographic (EEG) signal have been used to characterize the effects
      of opioids on the central nervous system. These parameters were formulated on an
      empirical basis. A new statistical method, semilinear canonical correlation, has
      been used to construct a new EEG parameter (a certain combination of the powers
      in the EEG power spectrum) that correlates maximally with the concentration of
      alfentanil at the effect site. To date, this new canonical univariate parameter
      (CUP) has been tested only in a small sample of subjects receiving alfentanil.
      METHODS: The CUP was tested on EEG data from prior studies of the effect of five
      opioids: alfentanil (n = 5), fentanyl (n = 15), sufentanil (n = 11), trefentanil
      (n = 5), and remifentanil (n = 8). We compared the CUP to the commonly used EEG
      parameter spectral edge, SE95%. The comparison was based on the signal to noise
      ratio, obtained by fitting a nonlinear pharmacodynamic model to both parameters.
      The pharmacodynamic parameter estimates obtained using both measurements were
      also compared. RESULTS: The values for signal-to-noise ratio were significantly
      greater for the CUP than for SE95% when considering all the opioids at once. The
      pharmacodynamic estimates were similar between the two EEG parameters and with
      previously published results. Semilinear canonical correlation coefficients
      estimated within each drug group showed patterns similar to each other and to the
      coefficients in the CUP, but different from coefficients for propofol and
      midazolam. CONCLUSIONS: Although the CUP was originally designed and tested using
      alfentanil, we have proven it to be a general measure of opioid effect on the
      EEG.

PMID- 7574055
TI  - Effects of perioperative analgesic technique on rate of recovery after colon
      surgery.
AB  - BACKGROUND: Choice of perioperative analgesia may affect the rate of recovery of
      gastrointestinal function and thus duration and cost of hospitalization after
      colonic surgery. METHODS: Fifty-four patients undergoing partial colectomy
      surgery were randomized into four groups. All groups received a standardized
      general anesthetic. Group MB received a preoperative bolus of epidural
      bupivacaine and morphine followed by an infusion of morphine and bupivacaine.
      Group M received a preoperative bolus of epidural morphine followed by an
      infusion of morphine. Group B received a preoperative bolus of bupivacaine
      followed by an infusion of bupivacaine. Group P received a preoperative bolus of
      intravenous morphine followed by intravenous patient-controlled morphine
      postoperatively. All patients participated in a standardized recovery program to
      minimize the influence of nonanalgesic factors on recovery of gastrointestinal
      function. All epidural groups were double-blinded. All patients were deemed ready
      for discharge according to prospectively defined criteria. RESULTS: Groups B and
      MB reported superior analgesia with activity (P < 0.01). Group M had a greater
      incidence of pruritus (P < 0.05). Group B had a greater incidence of orthostatic
      hypotension (P = 0.04). Groups B and MB recovered gastrointestinal function and
      fulfilled discharge criteria approximately 1.5 days earlier than groups M and P
      (P < 0.005). CONCLUSIONS: Epidural analgesia with bupivacaine and morphine
      provided the best balance of analgesia and side effects while accelerating
      postoperative recovery of gastrointestinal function and time to fulfillment of
      discharge criteria after colon surgery in relatively healthy patients within the
      context of a multimodal recovery program.

PMID- 7574056
TI  - Fluorine-19 nuclear magnetic resonance imaging and spectroscopy of sevoflurane
      uptake, distribution, and elimination in rat brain.
AB  - BACKGROUND: Determination of macroscopic and microscopic distribution of general
      anesthetics can facilitate identification of anatomic, cellular, and molecular
      loci of anesthetic action. Previous attempts to measure brain anesthetic
      distributions with fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging
      were conducted at magnetic field strengths lower than 2 Tesla. All have produced
      only silhouettes of brain tissue. Difficulties intrinsic to NMR imaging of
      anesthetics include higher anesthetic solubility in extracranial tissues and the
      lower limits to spin-echo delay times that can be used in conventional NMR
      imaging methods. So far, such methods have been unable to capture rapidly
      decaying brain 19F NMR signals. METHODS: 19F NMR imaging and spectroscopy were
      conducted at 4.7 Tesla using a specially developed NMR probe and new imaging
      methods. With the new techniques, it was possible to observe directly the uptake,
      distribution, and elimination in brain of sevoflurane, a fluorinated general
      anesthetic with special advantages for NMR investigations. RESULTS: 19F NMR
      images, acquired at different times after sevoflurane administration, clearly
      showed the distribution of a fluorinated general anesthetic within the brain.
      Based on continuous transverse relaxation time measurements, sevoflurane signals
      could be separated into two components, attributable respectively to sevoflurane
      in a mobile or immobile microenvironment. During washin, there was a delayed
      accumulation of anesthetic in the mobile microenvironment. During washout, there
      was a rapid elimination from the immobile microenvironment. CONCLUSIONS: At
      anesthetizing concentrations, sevoflurane distributes heterogeneously in the
      brain. Sevoflurane in the brain tissue contributes mostly to the immobile
      component of the 19F signal, whereas that in the surrounding adipose and muscle
      tissues contributes mostly to the mobile component. Imaging and spectroscopic
      results suggest that the immobile component of sevoflurane is associated with the
      general anesthetic effects of the agent.

PMID- 7574057
TI  - Prolonged alleviation of tactile allodynia by intravenous lidocaine in
      neuropathic rats.
AB  - BACKGROUND: Lidocaine may be useful in the treatment of neuropathic pain states.
      The authors hypothesized that lidocaine would reduce tactile allodynia observed
      in a rat nerve injury model. In an effort to determine the site of drug action,
      effects after intravenous, intrathecal, and regional administration were
      compared. METHODS: Rats underwent ligation of the left fifth and sixth lumbar
      spinal nerves. The 50% thresholds (g) for left hind paw withdrawal of awake rats
      to von Frey hairs were documented before, during, and after intravenous
      administration of lidocaine at programmed/documented pseudo-steady-state plasma
      concentrations, and correlated with measured plasma concentrations. Responses to
      lidocaine application intrathecally and regionally to the injured nerves were
      also recorded. RESULTS: In rats with tactile allodynia, intravenous lidocaine
      yielded 66 +/- 11% of the maximal possible effect on thresholds (100% = normal
      threshold), versus -1.3 +/- 2.7% for saline infusion. Twenty-one days after
      lidocaine infusion, 30-40% of the maximal possible effect persisted. Threshold
      increases depended on plasma concentration, rather than quantity of drug
      administered: rats receiving 15 mg/kg with higher plasma concentrations (1.2 +/-
      0.1 micrograms/ml) showed significant allodynia suppression throughout 7 days of
      follow-up, whereas rats receiving 15 mg/kg at a slower rate with lower plasma
      concentrations (0.6 +/- 0.1 microgram/ml) did not. The EC50 for acute allodynia
      suppression was 0.75 microgram/ml. No such allodynia suppression was seen after
      intrathecal or regional administration of lidocaine despite transient neural
      blockade. CONCLUSIONS: Intravenous, but not intrathecal or regionally applied,
      lidocaine produces dose-dependent suppression of allodynia associated with nerve
      injury. The effects far outlast plasma concentrations of lidocaine. The mechanism
      of these prolonged effects is unknown.

PMID- 7574059
TI  - In vitro effects of eltanolone on rat myocardium.
AB  - BACKGROUND: Eltanolone is a new short-acting intravenous induction agent.
      However, its effects on intrinsic myocardial contractility remain unknown.
      METHODS: The effects of eltanolone and its solvent (soya bean emulsion) on the
      intrinsic contractility of rat left ventricular papillary muscles were
      investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca2+ 0.5
      mM, stimulation frequency 12 pulses/min). We studied contraction; relaxation;
      contraction-relaxation coupling under high and low loads; and postrest
      potentiation. RESULTS: Eltanolone (0.1, 0.3, 1, 3, and 10 micrograms.ml-1)
      induced no significant inotropic effect, as shown by the lack of changes in
      maximum unloaded shortening velocity and active isometric force. Eltanolone did
      not significantly modify the contraction-relaxation coupling under low load,
      suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum.
      Eltanolone did not significantly modify the contraction-relaxation coupling under
      high load, suggesting that it did not modify calcium myofilament sensitivity.
      Eltanolone decreased the postrest potentiation in a concentration-dependent
      manner (from 150 +/- 14% to 118 +/- 9% at 10 micrograms.ml-1, P < 0.001),
      suggesting a decrease in the maximum capacity of calcium release by the
      sarcoplasmic reticulum, whereas its solvent did not. However, eltanolone did not
      slow postrest potentiation recovery, as shown by the absence of significant
      changes in the recovery slope, tau (4.5 +/- 1.4 vs. 3.8 +/- 1.0 beats; difference
      not statistically significant). CONCLUSIONS: Eltanolone induced no significant
      inotropic effect on rat myocardium. It induced a decrease in the calcium release
      function of the sarcoplasmic reticulum, but this effect was not sufficiently
      important to modify the inotropic properties.

PMID- 7574058
TI  - Heparin-protamine complexes cause pulmonary hypertension in goats.
AB  - BACKGROUND: Protamine reversal of heparin-induced anticoagulation causes
      thromboxane release followed by pulmonary vasoconstriction in sheep and pigs. The
      aim of this study was to determine whether heparin-protamine (H-P) complexes are
      causative agents of thromboxane release followed by pulmonary hypertension
      associated with protamine reversal of heparin. METHODS: We separated H-P
      complexes and non-heparin-protamine (non-H-P) complexes from heparinized
      defibrinated human plasma neutralized with protamine by chromatography and
      studied the changes in hemodynamics, airway pressure, and thromboxane B2
      concentration after injection of H-P complexes or non-H-P complexes into seven
      goats. In addition, we studied whether these pulmonary responses were blocked in
      goats pretreated with cyclooxgenase inhibitor (Indomethacin, n = 5) or
      thromboxane synthetase inhibitor (OKY-046, n = 5). RESULTS: A very small dose of
      H-P complexes increased pulmonary arterial and peak airway pressures and was
      followed by thromboxane B2 release (from 12 [5.5-23] to 28 [16-44] mmHg, from 9.0
      [7.5-15] to 12 [8-19] cmH2O, and from 0.85 [0.34-3.2] to 16.4 [1.4-39.3] ng.ml-1,
      respectively). On the other hand, animals that received non-H-P complexes showed
      no significant changes. Indomethacin totally blocked and OKY-046 partially
      blocked the increases in pulmonary arterial pressure and thromboxane B2
      concentration. CONCLUSIONS: H-P complexes play a major role in pulmonary
      hypertension after protamine reversal of heparin, and thromboxane A2 is a main
      mediator of the pulmonary hypertensive response to H-P complexes in goats.

PMID- 7574060
TI  - Inhaled anesthetics alter the determinants of coronary collateral blood flow in
      the dog.
AB  - BACKGROUND: Whether coronary steal is induced by inhaled anesthetic agents
      remains controversial in part because multiple factors determine collateral blood
      flow. METHODS: We used an established model to determine how halothane,
      isoflurane, and desflurane affect the hemodynamic determinants of coronary
      collateral blood flow. Twelve dogs were studied 4-5 weeks after ameroid
      constrictor implantation. Retrograde flow draining from the occluded artery was
      measured as an index of collateral flow after antegrade embolization. Pressure in
      the supplying artery at the origin of the collaterals was estimated with a stop
      flow technique. These techniques allow calculation of collateral segment
      resistance and the resistances of the supply artery upstream and downstream from
      the origin of the collaterals. RESULTS: None of the inhaled anesthetics affected
      collateral segment resistance. Downstream (arteriolar) resistance of the
      supplying artery was decreased by desflurane (-45%), isoflurane (-35%), and
      halothane (-15%), lowering pressure at the origin of the collaterals, an effect
      that was partially offset by a decrease in upstream resistance. Retrograde flow
      was unaffected by isoflurane and halothane but decreased by about 20% during
      desflurane administration. CONCLUSIONS: Inhaled anesthetics have many effects on
      segmental resistance and pressure in the coronary circulation. These findings
      help explain conflicting results from previous studies and provide a useful model
      for investigating the effects of inhaled agents on small coronary arteries.

PMID- 7574061
TI  - Propofol modulates the effects of chemoconvulsants acting at GABAergic,
      glycinergic, and glutamate receptor subtypes.
AB  - BACKGROUND: Propofol has been used to treat status epilepticus, but its use in
      patients with seizure disorders remains controversial, because of concerns that
      it produces paroxysmal motor phenomenon. Chemoconvulsants act by known discrete
      mechanisms and neurotransmitters, and therefore, they are useful tools for
      screening anticonvulsant activity. The main objective of this study was to
      characterize the effect of propofol pretreatment on convulsions induced by
      picrotoxin, bicuculline, and strychnine, all which decrease inhibitory
      neurotransmission, and by N-methyl-D-aspartic acid, kainic acid, and quisqualic
      acid, which enhance excitatory neurotransmission. METHODS: Groups of male Swiss
      Webster mice (n > or = 10/group) were given either vehicle (intralipid, 10 ml.kg
      1, control groups) or propofol (50 mg.kg-1, test groups) injected
      intraperitoneally. Five min after injection, convulsions were induced with either
      bicuculline (1.36-5.44 nmoles), picrotoxin (0.21-1 nmol), N-methyl-D-aspartic
      acid (0.51-2 nmol), quisqualic acid (1-10 nmol), kainic acid (0.252-2 mole), or
      strychnine (1.35-10.78 nmol) injected intracerebroventricularly. The number of
      animals with convulsions after each dose was recorded. Analysis of statistical
      significance was based on the log-probit lines of the quantal dose-response for
      the respective control and test groups, calculated 50% effective doses (ED50),
      the potency ratios (ED50higher/ED50lower) and their 95% confidence limits.
      RESULTS: Propofol pretreatment decreased the potency ratio of both bicuculline
      (0.47, 95% confidence interval = 0.23-0.94) and picrotoxin (0.61, 0.47-0.79),
      signifying an anticonvulsant effect. Conversely, propofol pretreatment
      significantly enhanced the convulsive potency of kainic acid (potency ratio and
      95% confidence interval = 1.66, 1.21-2.29), quisqualic acid (3.17, 1.98-5.09),
      and strychnine (1.76, 0.79-3.89). CONCLUSIONS: Current results suggest that
      propofol augments the paroxysmal motor phenomenon induced by kainic acid,
      quisqualic acid, and strychnine. This action may be, at least partly, responsible
      for the motor manifestations reported after propofol administration. These in
      vivo results on modulation of gamma-aminobutyric acid, glycine, alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptor-mediated
      transmission may be of significance in understanding the mechanism of propofol
      action at the excitatory and inhibitory amino acid receptors.

PMID- 7574062
TI  - Role of pertussis toxin-sensitive G-proteins in the analgesic and anesthetic
      actions of alpha 2-adrenergic agonists in the rat.
AB  - BACKGROUND: alpha 2 Adrenoceptors are coupled to G-proteins sensitive to
      pertussis toxin (PTX) in the locus coeruleus. At this site, the hypnotic response
      to dexmedetomidine, an alpha 2 agonist, can be blocked by pretreatment with PTX.
      G-proteins sensitive to PTX may also be involved in the transduction of
      anesthetic and analgesic responses to alpha 2 agonists at supraspinal or spinal
      sites. To address this question the effects of pretreatment with PTX administered
      intracerebroventricularly, intrathecally, or a combination of the two were
      examined on the MAC for halothane, and the anesthetic-sparing and analgesic
      effects of a systemically administered alpha 2 agonist, dexmedetomidine. METHODS:
      Rats were cannulated intracerebroventricularly, intrathecally, and with a
      combination of intracerebroventricular/intrathecal and treated with PTX (0 and
      2.5 micrograms intracerebroventricularly; 0 or 0.5 microgram intrathecally; 0 + 0
      or 2.5 + 0.5 intracerebroventricular-intrathecal)). After 7 days, either the
      analgesic (tail-flick latency) or the MAC-sparing effects of a calculated 50%
      effective dose of dexmedetomidine were measured. To confirm that
      intracerebroventricularly administered PTX was effective, ribosylation of G
      proteins was assessed in periventricular brain tissue. RESULTS: The analgesic
      action of dexmedetomidine was blocked by PTX intrathecally but not by PTX via the
      intracerebroventricular route. The MAC-sparing action of dexmedetomidine was not
      blocked by PTX via the intrathecal or intracerebroventricular routes alone or in
      combination. Yet, intracerebroventricularly administered PTX effectively
      ribosylated the G-proteins. CONCLUSIONS: Taken together with the authors'
      previous report, these data suggest that the hypnotic and the analgesic responses
      to dexmedetomidine are transduced via PTX-sensitive G-protein-coupled alpha 2
      adrenoceptors but at separate sites (analgesic-spinal; hypnotic-locus coeruleus).
      Further studies are needed to localize the precise site(s) for the MAC-sparing
      effect of dexmedetomidine and to establish whether PTX-sensitive G-proteins are
      involved in this response.

PMID- 7574063
TI  - Halothane and isoflurane inhibit endothelium-derived relaxing factor-dependent
      cyclic guanosine monophosphate accumulation in endothelial cell-vascular smooth
      muscle co-cultures independent of an effect on guanylyl cyclase activation.
AB  - BACKGROUND: Interaction of inhalational anesthetics with the nitric oxide
      signaling pathway and the mechanism of such effects are controversial. The aim of
      this study was to clarify the sites and mechanism of inhalational anesthetic
      interaction with the vascular nitric oxide and guanylyl cyclase signaling
      pathway. METHODS: To specifically study the mechanism of anesthetic interaction
      with the nitric oxide-guanylyl cyclase pathway, cultured vascular smooth muscle
      and endothelial cell-vascular smooth muscle (EC-VSM) co-culture models were
      chosen. Monolayer cultures of VSM with or without cultured endothelial cells
      grown on microcarrier beads were preequilibrated with anesthetic and stimulated
      with agonists. The effect of inhalational anesthetics on cyclic guanosine
      monophosphate (GMP) content of unstimulated VSM and of VSM in which soluble
      guanylyl cyclase had been activated by the endothelium-independent
      nitrovasodilators, sodium nitroprusside, nitroglycerin, or nitric oxide was
      determined. Experiments were also performed to assess the effect of inhalational
      anesthetics on unstimulated endothelial cell-vascular smooth muscle co-cultures
      and on co-cultures in which nitric oxide synthase and subsequent cyclic GMP
      production had been activated by the receptor-mediated agonists bradykinin and
      adenosine triphosphate and by the non-receptor-mediated calcium ionophore A23187.
      RESULTS: Increasing concentrations of halothane and isoflurane from 0.5 to 5% had
      no effect on basal cyclic GMP concentrations in cultured VSM alone or in
      endothelial cell-vascular smooth muscle co-cultures, and had no effect on sodium
      nitroprusside, nitroglycerin, or nitric oxide stimulated cyclic GMP accumulation
      in cultured VSM. In agonist-stimulated co-cultures, however, halothane and
      isoflurane significantly (P < 0.05) inhibited increases in cyclic GMP
      concentration in response to both receptor- and non-receptor-mediated nitric
      oxide synthase activating agents. CONCLUSIONS: Inhalational anesthetics do not
      stimulate or inhibit basal cyclic GMP production in co-cultures or VSM,
      suggesting that inhalational anesthetics do not activate soluble or particulate
      guanylyl cyclase and do not activate nitric oxide synthase. Inhalational
      anesthetics do not inhibit nitrovasodilator-induced cyclic GMP formation,
      suggesting a lack of interference with soluble guanylyl cyclase activation.
      Inhalational anesthetics inhibit both agonist and calcium ionophore-stimulated
      nitric oxide-dependent cyclic GMP accumulation in endothelial cell-vascular
      smooth muscle co-cultures. Consistent with previous vascular ring studies,
      anesthetics appear to inhibit nitric oxide-guanylyl cyclase signaling distal to
      receptor activation in the endothelial cell and proximal to nitric oxide
      activation of guanylyl cyclase.

PMID- 7574064
TI  - Chest wall responses to rebreathing in halothane-anesthetized dogs.
AB  - BACKGROUND: The pattern of respiratory muscle use during halothane-induced
      anesthesia differs markedly among species breathing quietly. In humans, halothane
      accentuates phasic activity in rib cage and abdominal expiratory muscles, whereas
      activity in the parasternal intercostal muscles is abolished. In contrast,
      halothane abolishes phasic expiratory muscle activity during quiet breathing in
      dogs, but parasternal muscle activity is maintained. Respiratory muscle responses
      to CO2 rebreathing were measured in halothane-anesthetized dogs to determine if
      species differences present during quiet breathing persist over a wide range of
      central respiratory drive. METHODS: Chronic electromyogram electrodes were
      implanted in three expiratory agonists (the triangularis sterni, transversus
      abdominis, and external oblique muscles) and three inspiratory agonists (the
      parasternal intercostal muscle, costal and crural diaphragm) of six mongrel dogs.
      After a 1-month recovery period, the dogs were anesthetized in the supine
      position with halothane. The rebreathing response was determined by Read's method
      during anesthesia with stable 1 and 2 minimum alveolar end-tidal concentrations
      of halothane. CO2 concentrations were measured in the rebreathing bag using an
      infrared analyzer. Chest wall motion was measured by fast three-dimensional
      computed tomographic scanning. RESULTS: Halothane concentration did not
      significantly affect the slope of the relationship between minute ventilation
      (VE) and PCO2 (0.34 +/- 0.04 [M +/- SE] and 0.28 +/- 0.05 l.min-1.mmHg-1 during 1
      and 2 minimum alveolar concentration anesthesia, respectively). However, 2
      minimum alveolar concentration anesthesia did significantly decrease the
      calculated VE at a PCO2 of 60 mmHg (from 7.4 +/- 1.2 to 4.0 +/- 0.6 l.min-1),
      indicating a rightward shift in the response relationship. No electromyographic
      activity was observed in any expiratory muscle before rebreathing. Rebreathing
      produced electromyographic activity in at least one expiratory muscle in only two
      dogs. Rebreathing significantly increased electromyographic activity in all
      inspiratory agonists. Rebreathing significantly increased inspiratory thoracic
      volume change (delta Vth), with percentage of delta Vth attributed to outward rib
      cage displacement increasing over the course of rebreathing during 1 minimum
      alveolar concentration anesthesia (from 33 +/- 6% to 48 +/- 2% of delta Vth).
      CONCLUSIONS: Rebreathing did not produce expiratory muscle activation in most
      dogs, demonstrating that the suppression of expiratory muscle activity observed
      at rest persists at high levels of ventilatory drive. Other features of the
      rebreathing response also differed significantly from previous reports in
      halothane-anesthetized humans, including (1) an increase in the rib cage
      contribution to tidal volume during the course of rebreathing, (2) recruitment of
      parasternal intercostal activity by rebreathing, (3) differences in the response
      of ventilatory timing, and (4) the lack of effect of anesthetic depth on the
      slope of the ventilatory response. These marked species differences are further
      evidence that the dog is not a suitable model to study anesthetic effects on the
      activation of human respiratory muscles.

PMID- 7574065
TI  - Characteristics of the analgesic effects and drug interactions of intrathecal
      carbachol in rats.
AB  - BACKGROUND: Intrathecal carbachol produces consistent analgesia in animals
      without appreciable adverse effects. Little is known about the ability of this
      drug to provide analgesia as stimulus intensity is increased. Likewise, there are
      few data regarding interactions between carbachol and other intrathecal
      analgesics. METHODS: Using two different noxious radiant heat intensities, one
      applied to each hind limb, analgesic effects of 1, 3, 10, and 30 micrograms
      intrathecal carbachol on paw withdrawal latencies were measured. Similar testing
      was done for intrathecal morphine and clonidine. ED50 fractions (1/2, 1/4, 1/8,
      1/16) of drug combinations of carbachol-morphine and carbachol-clonidine were
      administered, responses to the low intensity stimulus were recorded, and the ED50
      of each combination was established and isobolographic analysis of the drug
      interactions was carried out. RESULTS: The 30-micrograms dose of carbachol was
      associated with transient agitation, salivation, and hind limb weakness. No other
      adverse effects were noted. The ED50 (95% confidence interval) of intrathecal
      carbachol was 2.34 micrograms (1.34-4.04) for low intensity stimulation and 12.64
      micrograms (4.18-38.25) for high intensity. There was no significant difference
      between high- and low-intensity ED50 values for intrathecal morphine and
      clonidine. The analgesic effect of the carbachol-morphine and carbachol-clonidine
      combinations were significantly greater than the calculated additive effects. The
      ED50 for the carbachol-morphine combination was 12% of the expected additive
      value and the ED50 for the carbachol-clonidine combination was 30% of the
      expected additive value. CONCLUSIONS: Intrathecal carbachol provides analgesia to
      noxious thermal stimulation of the hind paw in rats. It is relatively less
      effective at providing analgesia than intrathecal morphine or clonidine when
      stimulus intensity is raised. Intrathecal carbachol is synergistic when combined
      with intrathecal morphine or clonidine.

PMID- 7574067
TI  - Epidural and intravenous opioid-induced neuroexcitation.

PMID- 7574066
TI  - Hepatic heat shock and acute-phase gene expression are induced simultaneously
      after celiotomy in the anesthetized pig.
AB  - BACKGROUND: The liver plays a central role in the whole organism's response to
      injury. Expression of hepatic acute-phase and heat-shock genes likely contributes
      to the restoration of homeostasis after stressful events. However, after
      prolonged ischemia, hepatic transcription of heat-shock genes can exclude the
      simultaneous transcription of acute-phase genes. The issue of whether hepatic 72
      kd heat-shock protein (hsp72) gene expression is induced under perioperative
      conditions that do not result in prolonged liver ischemia and whether this might
      further affect the expression of the acute-phase reactant inter-alpha-trypsin
      inhibitor (alpha-Ti) was examined. METHODS: Pigs were anesthetized with sodium
      pentobarbital and ketamine hydrochloride, tracheally intubated, and their lungs
      ventilated. After celiotomy, a hepatic biopsy sample was obtained. Arterial blood
      pressure, cardiac output, and total hepatic blood flow were measured. Subsequent
      biopsies were obtained at 1, 2, 3, 4, and 6 h after the initial biopsy. Arterial
      norepinephrine concentrations were measured using high-pressure liquid
      chromatography. Nuclear runoff (run on) analysis and Northern blotting were
      applied to estimate changes in hsp72 and alpha-Ti gene transcription rates and
      RNA levels. Western blotting was used to estimate changes in hsp72 levels.
      RESULTS: Hemodynamic parameters did not change significantly over time. Arterial
      norepinephrine concentrations were increased at all time points. Hepatic hsp72
      RNA levels increased up to sixfold while nuclear runoff assays did not detect
      significant changes in hsp72 gene transcription rates. The increases in hsp72 RNA
      levels correlated with accumulation of hsp72 (up to sevenfold). Increases in
      alpha-Ti transcription rates up to 42-fold were associated with respective
      increases in alpha-Ti RNA levels (up to 17-fold). CONCLUSIONS: These data
      demonstrate that hepatic expression of hsp72 is not confined to conditions that
      lead to prolonged liver ischemia but is also part of the response of the liver to
      surgery under general anesthesia. Furthermore, these conditions are permissive
      for the simultaneous RNA expression of the acute-phase reactant alpha-Ti.

PMID- 7574068
TI  - Severe neurologic deficit after nitrous oxide anesthesia.

PMID- 7574069
TI  - Impossible insertion of the laryngeal mask airway and oropharyngeal axes.

PMID- 7574072
TI  - Propofol in the management of myoclonus syndrome induced by chloralose poisoning.

PMID- 7574070
TI  - Acute toxic delirium: an uncommon reaction to transdermal fentanyl.

PMID- 7574071
TI  - Intraabdominal fire during laparoscopic cholecystectomy.

PMID- 7574073
TI  - Femororadial pressure-delta and thermoregulation.

PMID- 7574074
TI  - End-tidal carbon dioxide monitoring may help diagnosis of H-type
      tracheoesophageal fistula.

PMID- 7574075
TI  - Reply from Compressed Gas Association, Inc.

PMID- 7574076
TI  - Another way through a laryngeal mask airway.

PMID- 7574077
TI  - Atypical cholinesterase in a patient with situs inversus totalis.

PMID- 7574078
TI  - Ventilator circuit changes and nosocomial pneumonia.

PMID- 7574080
TI  - The Penn State Anesthesia Electronic Case Conference.

PMID- 7574079
TI  - Low-frequency component of heart rate variability.

PMID- 7574083
TI  - Intubation through the laryngeal mask airway.

PMID- 7574081
TI  - Coma and vegetative state are not interchangeable terms.

PMID- 7574082
TI  - Carbon dioxide reactivity and cerebral ischemia: is the cortical somatosensory
      evoked potential a sensitive detector of cerebral ischemia?

PMID- 7574084
TI  - Effect of storage of samples at -80 degrees C on the assay of lipoprotein(a) by
      rate nephelometry (Beckman 360 Array).
AB  - The effect of storage of samples on the assay of lipoprotein(a) depends on the
      technique used. We have tested the automated Beckman 360 Array rate nephelometer
      using Dako anti-Lp(a) antibody, and an Immunofrance standard and control serum
      according to the technique of Gillery et al. We found a very high correlation
      between serum concentrations before freezing and those after three weeks and six
      months at -80 degrees C. Variations greater than 15% concerned only low levels of
      Lp(a) and were probably related to the precision of the technique at low
      concentrations.

PMID- 7574085
TI  - [Genotyping of apolipoprotein E (alleles epsilon 2, epsilon 3 and epsilon 4) from
      capillary blood].
AB  - A technique to determine epsilon 2, epsilon 3 and epsilon 4 alleles expressed at
      the apolipoprotein E locus (apoE genotype) is described. The proposed method is
      convenient for detecting this polymorphism on capillary blood spots. Capillary
      blood is collected on absorbent paper allowing transmission by post and prolonged
      conservation of samples. Even when the amount of DNA is very small, double
      amplification by polymerase chain reaction (PCR) from a DNA fragment comprising
      the two polymorphic sites enables the length of the synthetized fragment to be
      measured the amplification of all samples to be verified, thus avoiding false
      interpretations resulting from a 51-base-pair fragment due to primer self
      hybridization. The digestion of this fragment by Hha I restriction enzyme and
      electrophoresis of the digested products give an unambiguous diagnosis of the six
      most frequent (epsilon 2/epsilon 2, epsilon 3/epsilon 3 epsilon 4/epsilon 4,
      epsilon 2/epsilon 3, epsilon 2/epsilon 4, and epsilon 3/epsilon 4). Intended for
      genotype screening determinations, this technique is not convenient for all rare
      apoE variants, which must be determined by plasma isoelectrofocusing or genomic
      DNA sequencing. The technique may be done performed any time, even if the subject
      is not fasting. It avoids the difficulties of interpretation of the
      isoelectrophoretic patterns induced by poor conservation of the samples or the
      presence of sialylated isoforms of apoE or other contaminant proteins. The modest
      cost of the proposed technique allows determination of the apoE genotype in large
      series.

PMID- 7574086
TI  - Clinical evaluation of the Vital system compared with the Hemoline diphasic
      method for the detection of aerobic blood cultures.
AB  - In a collaborative study at two university hospitals, the recovery of
      microorganisms and the speed of detection of microbial aerobic growth by the
      Vital system (bioMerieux) and a diphasic conventional blood culture system were
      compared. The Vital system monitors each blood culture bottle every 15 minutes to
      detect inactivation of fluorescent suspended in the broth medium due to microbial
      growth. A total of 1086 comparisons were made between the two systems, yielding a
      total of 117 isolates. Microorganisms were recovered more often from the Vital
      aerobic bottles (p < 0.05). The Vital system detected 43% of the microorganisms
      within the first 12 hours of incubation whereas in the same time the conventional
      system detected only 5% of the microorganisms. The results demonstrate that the
      Vital system is a reliable, continuous monitoring, fully automated system and an
      attractive alternative to conventional blood culture methods.

PMID- 7574087
TI  - Automated blood culture systems.
AB  - This review compares automated systems of blood culture for the detection of
      positive bottles, excluding mycobacteria. The performance of different systems is
      influenced by several key variables, including volume of the blood sample, the
      use of resins, shaking to increase the recovery of aerobic microorganisms,
      duration of incubation and final subculture. The Bactec, BacT/Alert, BioArgos and
      ESP systems require further study and technical improvement. There is no single
      ideal system of blood culture, and combinations of two or more methods are likely
      to provide the best results.

PMID- 7574088
TI  - Determination of doxycycline in human plasma and urine samples by high
      performance liquid chromatography. Application for drug monitoring in malaria
      chemoprophylaxis.
AB  - A reverse-phase high performance liquid chromatographic method with ultraviolet
      detection is described for the measurement of doxycycline in human plasma and
      urine. After liquid-solid extraction on a Bond Elut C18 cartridge, doxycycline
      and demeclocycline (internal standard) are separated on a Novapak C18 column by
      isocratic elution. The mobile phase consists of acetonitrile-oxalate buffer, pH
      2.3 (25:75; v/v). The eluent is monitored with an ultraviolet detector at 355 nm.
      The lower limit of quantification in plasma is close to 25 ng/ml. No
      chromatographic interference can be detected from endogenous compounds,
      tetracycline group antibiotics or antimalarial drugs. The method is accurate and
      precision is good with inter- and intra-assay relative standard deviations lower
      than 6.7%. The chromatographic procedure takes 8 minutes and can be used for
      therapeutic drug monitoring, clinical and pharmacokinetic studies.

PMID- 7574089
TI  - [Determination of plasma proinsulins, insulin and C-peptide].
AB  - Insulin is synthesized from a precursor, proinsulin, then converted in the beta
      cell by sequential limited proteolysis into insulin and C-peptide, which are
      stored in secretory granules derived from the Golgi apparatus. Since this process
      is incomplete, some intact and partially processed proinsulins (split
      proinsulins) remain trapped in the granules and enter the circulation with
      insulin and C-peptide. As proinsulins are present in low concentration in serum
      and show structural homology with insulin and C-peptide, only two-site
      immunoassays using monoclonal antibodies can achieve sensitive and specific
      measurements of their intact and split forms. Insulin radioimmunoassays using
      polyclonal antibodies are not specific since such antibodies cross-react with
      proinsulins. Two-site immunoassays using monoclonal antibodies improve the
      specificity and the sensitivity of insulin determination. C-Peptide concentration
      is measured by radioimmunoassays using polyclonal antibodies which cross-react
      with proinsulins.

PMID- 7574090
TI  - Serum galactosyltransferase activities in newborn children and pregnant women.
AB  - We have compared serum galactosyltransferase activity in pregnant women and in
      newborn children. Subjects in this study were 75 women at different stages of
      pregnancy and 60 newborns, including premature infants. Activity ratios in
      pregnant women are based on the period of gestation, expressed in weeks of
      amenorrhea. Average values were 265 nmol/h/ml for up to 12 weeks of amenorrhea,
      369 from 13 to 28 weeks and 483 over 28 weeks versus 232 nmol/h/ml for non
      pregnant women. In infants, galactosyltransferase activity decreased with
      increasing age from conception, but the activity level was always much higher in
      newborns than in women at the ninth month of pregnancy. We discuss the origin of
      the enzyme in these various samples.

PMID- 7574092
TI  - [A case of visceral leishmaniasis in a non-immunosuppressed patient].

PMID- 7574091
TI  - [Lipoprotein lipase deficiency due to lipoprotein lipase gene mutations (current
      overview)].

PMID- 7574094
TI  - Detection of breast tumor progesterone receptor isoforms with the PR-enzyme
      immunoassay kit (Abbott). Effect of heat shock proteins on epitope recognition.
AB  - Eighty-nine human breast tumor progesterone receptors were assayed both by a
      radioligand assay (RLA; 3H-ORG-2058) and by the enzyme immunoassay from Abbott
      Laboratories (PR-EIA). The correlation obtained between the two methods was EIA =
      0.83 RLA + 4.1 fmol/mg protein (r = 0.83). Great discrepancies were observed with
      EIA/RLA ratios varying from 0.5 to 2. After KCl 0.4 mol/l dissociation and
      chromatographic separation of 8 PR isoforms [12], the two PR polymeric forms
      (isoforms 1 and 2) which remained bound to the hsp90 heat shock protein were not
      or only partially detected by EIA, whereas PR-hsp70 isoforms were highly detected
      with EIA/RLA ratios increased up to 3.8. Free PR-A and PR-B proteins and the PR
      truncated form (52 kDa) were never detected by EIA. Thus, the final result of PR
      assay using the Abbott method depends directly on the amount of PR-hsp70 isoforms
      produced through KCl dissociation during the overnight incubation of PR with the
      KD68 coated beads.

PMID- 7574093
TI  - [Apropos of pooling biologic specimens before the measurement of a constituent or
      a property].

PMID- 7574095
TI  - [Value of immunoassay of hCG for the determination of high plasma
      concentrations].
AB  - The serum concentration of human chorionic gonadotrophin is higher in trisomy 21
      than in normal pregnancy. Our study aimed at comparing 17 commercial kits, both
      those for measuring high concentrations and others for diagnosis and initial
      follow-up of pregnancy under specific conditions, ie for measuring hCG
      concentrations between weeks 14 and 18 of pregnancy. All kits were satisfactory;
      however, usual values for the gestational weeks concerned need to be established
      for each reagent.

PMID- 7574096
TI  - Serum 5'-nucleotidase and alkaline phosphatase activities after high dose
      chemotherapy and bone marrow transplantation in cases of malignancy in children.
AB  - After bone marrow transplantation in children, it is essential to detect
      secondary liver diseases and hepatotoxic effects of immunosuppressive therapy.
      These can be revealed by cytolytic syndromes sometimes associated with
      cholestasis. It is therefore important to find an early and specific cholestasis
      enzymatic marker. A retrospective study of the changes in levels of biological
      parameters has been carried out in 13 children who underwent one or more bone
      marrow transplantations. During the 3 months following bone marrow
      transplantation, all patients developed liver injury characterized by an early
      and very elevated 5'-nucleotidase activity (sometimes more than 40 times the
      upper reference limit), a moderate increase in alkaline phosphatase activity, a
      variable increase in alanine aminotransferase activity and inconstant changes in
      total bilirubin levels. These results show that cytolytic syndrome and
      cholestasis are often associated with increases in 5'-nucleotidase and alkaline
      phosphatase activities. These increases are not correlated, probably due to the
      influence of therapy on the synthesis and release of both enzymes in the liver.
      5'-nucleotidase seems to be the best marker for the detection and follow-up of
      liver disease in this patient group.

PMID- 7574097
TI  - [Orosomucoid prealbumin ratio in bronchopulmonary cancers].
AB  - Lung cancer is a common pathology with high mortality due to late diagnosis. The
      1987 TNM classification clearly defines the different steps and their prognosis.
      Although the prognostic value of some biological parameters (mainly serum LDH,
      sodium and/or albumin) has been established, these are not much used. We have
      prospectively studied the serum levels of seven proteins (RBP, prealbumin,
      albumin, transferrin, haptoglobin, orosomucoid, CRP) and we demonstrate the
      predominant value of prealbumin for the establishment of the prognosis of lung
      cancer; determination of orosomucoid increases the prognostic value of
      prealbumin. We confirm, for lung cancer, the prognostic value of the orosomucoid
      prealbumin ratio, already known for other cancers.

PMID- 7574099
TI  - [Interference of dysglobulinemia and lactescence on serum phosphate
      determination: an easy and efficient correction].

PMID- 7574098
TI  - [Evaluation, by flow cytometry, of activated platelet levels after coronarography
      and intraluminal angioplasty].
AB  - Coronarography and intraluminal angioplasty induce platelet activation. In this
      study, activated platelets were evaluated by measuring platelet-bound fibrinogen
      using a polyclonal fluorescent antibody in flow cytometry on whole blood. For
      normal subjects, the percentage of platelets binding fibrinogen was low (16.67%)
      and reached 81.0% in response to ADP. The percentages of platelets binding
      fibrinogen were evaluated 24 hours before and after coronarography. During
      intracoronary angioplasty, blood was collected from the catheter before and after
      the dilation and aspirin bolus (1 g). In both groups, the percentages of
      activated platelets were lower compared with those of the control group
      (respectively 3.96% and 5.59% versus 16.67%) following aggregation inhibitor,
      anticoagulant and calcium inhibitor therapies. Twenty-four hours after
      coronarography, platelet activation was noted (9.71% versus 3.96%). During
      angioplasty no significant activation was observed immediately after dilation
      (6.54% versus 5.59%). In both groups before the intervention, ADP stimulation was
      still responsible for platelet activation but to a lesser extent than in the
      control group (60.42% and 66.31% versus 81.0%). After coronarography, the
      platelet response to ADP was identical to that in the control group (81.01%
      versus 81.0%). Immediately after dilation, this activation was not observed in
      patients with an angioplasty. This study shows that platelet activation occurs 24
      hours after coronarography, whereas after dilation and an aggregation inhibitor
      bolus this activation is not observed during angioplasty.

PMID- 7574100
TI  - [Contribution of ion exchange chromatography of amino acids to the diagnosis of
      aspartylglucosaminuria].

PMID- 7574101
TI  - [Improvement of result coherence in clinical enzymology: multicenter study of
      gamma-glutamyltransferase, alkaline phosphatase and amylase activities].
AB  - We report here on the results of a multicenter study of three enzyme activities
      (gamma-glutamyltransferase, alkaline phosphatase and amylase). For each activity,
      measurements were performed in two laboratories on different series of patients'
      specimens under routine conditions, at 30 and 37 degrees C, with techniques
      frequently used in France and with the IFCC reference method, when it exists. For
      each technique, precision was acceptable, but results differed considerably
      according to the technique used. The study also showed that for different
      techniques it is not possible to use a single transformation factor for
      activities between 30 and 37 degrees C. Patients' results determined by two
      techniques often showed a constant relationship. Groups of techniques that
      determined the same catalytic activity in patients' specimens were identified,
      whereas other techniques did not have this property. Several preparations,
      including reference materials produced by the Community Bureau of Reference
      (European Community, Brussels) and ten commercial secondary materials were tested
      for similar behaviour as compared to patients' samples. Results show the
      commutability of reference materials within a group of techniques indicating that
      they can be used as calibrators. This was seldom the case for the commercial
      secondary materials and we did not find any such material suitable for
      calibration of the three enzymatic activities. The present study demonstrates
      that with defined techniques and validated calibrators it is possible to reduce
      considerably differences between results obtained with different techniques at
      different temperatures and in different laboratories.

PMID- 7574102
TI  - Recommendations for the biometrical evaluation of method comparison. Results from
      patients' samples.

PMID- 7574103
TI  - [Antiplatelet glycoprotein monoclonal antibodies: properties and practical
      value].
AB  - The aim of this review is (i) to classify the different monoclonal antibodies
      against platelet glycoproteins according to their properties and (ii) to take
      stock of their many diagnostic and therapeutic uses. Most of these antibodies
      recognize antigens on resting platelets without inducing activation, sometimes
      however they inhibit platelet function. Some of these antibodies, especially
      those against specific antigens (GPIIb/IIIa, CD9, CD36), have the capacity to
      activate platelets in vitro, either by direct binding of antibodies on the
      antigen or through the Fc domain binding to its platelet receptor Fc gamma RII.
      Other antibodies are directed against activation-dependent antigens that are
      expressed as a result of (i) a modification of a glycoprotein structure during
      platelet activation (as for GPIIb/IIIa), (ii) platelet release of granular
      antigens (GMP140, CD63, granulophysin...) or (iii) binding of soluble antigens on
      the activated platelet surface. Monoclonal antibodies find practical applications
      for both in vitro and in vivo diagnosis of bleeding or thrombotic pathology with
      some of them, notably anti-GPIIb/IIIa, having a promising future for
      antithrombotic therapy.

PMID- 7574104
TI  - [Biology of the endothelial cell and atherogenesis].
AB  - Through their specific biological properties, vascular endothelial cells play a
      major role in maintaining the homeostasis of the cardiovascular system. The
      vascular endothelium participates actively in coagulation and fibrinolysis,
      contributes to regulating vascular tone, is involved in inflammation and
      immunological responses, produces several different stromal components, plays a
      crucial role in angiogenesis and wound-healing, and interacts with plasma
      lipoproteins. These physiological functions of endothelial cells are triggered by
      different endothelium derived mediators and are regulated by numerous
      environmental factors that can markedly modulate the functional state of these
      cells by affecting their biosynthetic capabilities, giving them different
      phenotypes in native, activated and injured states. Excessive endothelial
      activation leads to changes in endothelial cell gene expression, leading to what
      is referred to as a dysfunctional state. In this non-adaptative functional state,
      endothelial cells lose the ability to adjust, within the physiological range,
      some of their constitutive functions and express newly induced molecules, some of
      which act as proatherosclerotic factors. Activated endothelial cells thus
      participate actively in the pathogenesis of atherosclerosis.

PMID- 7574105
TI  - [Study of epitopic sites of the major bullous pemphigoid antigen (BPAg1)].
AB  - Bullous pemphigoid is an acquired blistering skin disease associated with the
      production of IgG autoantibodies to 230 kDa BP Ag (BPAg1) and to 180 kDa BP Ag
      (BPAg2). The aim of our work was to better characterize the epitopes of BPAg1.
      For this, we firstly generated a bullous pemphigoid recombinant protein of 55 kDa
      Mr (rBP55) from a cDNA sequence encoding for the carboxyterminal region of the
      230 kDa BP antigen. Ninety-two percent of sera from patients with autoantibodies
      to the 230 kDa polypeptide recognized the rBP 55 protein. These results confirm
      that this 555 aminoacid segment corresponding to rBP 55 contains major epitopes.
      In order to study the epitopes of the amino-terminal portion of the BPAg1
      antigen, we generated immortalized B cell lines secreting human monoclonal
      antibodies to BPAg1 from two patients whose sera reacted with native BPAg1 but
      not with the recombinant rBP55 carboxy-terminal peptide. Blocking
      immunofluorescence experiments and phylogenetic studies showed that these human
      monoclonal antibodies recognize different epitopes of BPAg1. According to these
      studies, we can conclude on the wide variety of epitopes recognized by BPAg1
      autoantibodies.

PMID- 7574106
TI  - Application of R-charts to detection of random errors: a computer simulation
      study.
AB  - The application of R-charts to quality control in clinical chemistry was
      investigated. These charts are widely used in statistical process control and
      plot the range (ie the difference between the highest and the lowest values) of a
      set of controls. A set of five control serums was considered. A computer
      simulation program was developed for this investigation. It showed a power
      function that is remarkably insensitive to systematic errors. Consequently these
      charts may be a useful tool in discriminating between systematic and random
      errors, helping the trouble-shooting significantly, if used concurrently with
      Levey-Jennings' charts. Nevertheless, as several control samples are necessary,
      this technique is not cost-effective for short analytical runs.

PMID- 7574107
TI  - [Compared diagnostic performances of CKMB measurements by immuno-inhibition and
      three immunoenzyme methods for the early diagnosis of myocardial infarction].
AB  - In 98 patients consecutively admitted in a medical intensive care unit, an
      aliquot taken from the blood sample withdrawn for the cardiac enzyme admission
      request has been frozen. After thawing of these 98 aliquots total CK and the
      creatine kinase MB isoenzyme were measured on the same day. For this last
      determination, four methods were used and compared: an immunoinhibition method
      (Merck) and three immunoenzymatic assays (Abbott on IMX; Baxter on Stratus II;
      Hybritech on single use Icon cylinder). In 19 out of the 98 patients studied the
      diagnosis of myocardial infarction was made retrospectively by a cardiologist.
      This diagnosis was established according to the criteria defined by the WHO. The
      clinical performances (sensitivity, specificity, positive predictive value,
      negative predictive value) have been calculated for each test according to the
      following criteria: on the one hand, a cut-off of 8% (reference range of our
      laboratory) for the immunoinhibition technique; on the other hand, a cut-off
      defined by the manufacturer together with a cut-off obtained from the ROC curves
      for the three immunoenzymatic assays. Our results clearly demonstrate that the
      clinical performances of the three immunoenzymatic CKMB assays are very
      comparable and appear to be much better than the immunoinhibition method which
      should be abandoned.

PMID- 7574108
TI  - [Value of transgenic mouse as model for the study of human lipoprotein
      metabolism].
AB  - Lipoprotein transport genes have been used to make either transgenic or knockout
      mice with altered lipoprotein levels and metabolism. These models have provided
      information in at least three major issues. First, transgenic mice allow to study
      gene expression regulation. This approach has been helpful in identifying tissue
      specific expression of two clusters of apolipoprotein genes apo E/CI/CII and apo
      AI/CIII/AIV. Another example is the identification of a cis-acting region
      controlling transcription of the CETP gene in response to diet. Second,
      transgenic mice model provides relevant insights into lipoprotein metabolism: the
      structural role of human apo AII, the effect of apo AI on HDL subfractions
      distribution, the contribution of apo CIII to hypertriglyceridemia, and by
      contrast of apo E in the clearance of atherogenic TG rich lipoproteins, the role
      of CETP in the balance of LDL and HDL concentration and distribution. Finally,
      certain strains of mice under specific conditions of diet develop atherosclerotic
      lesions which have been shown to be reduced in human apo AI transgenic animals.
      However, the best mouse model for further investigation of human atherosclerosis
      seems to be apo E knockout mice.

PMID- 7574109
TI  - Auxacolor, a new commercial system for yeast identification: evaluation of 182
      strains comparatively with ID 32C.
AB  - The incidence of deep candidiasis, particularly in immunocompromised patients,
      and the emergence of less sensitive yeast species to new antifungal agents
      explain the interest of their rapid identification. A new identification system,
      Auxacolor (Sanofi Diagnostics Pasteur), has been evaluated, comparatively to ID
      32C strip taken in reference (bioMerieux SA). These systems include respectively
      13 and 29 carbohydrate assimilation tests. One hundred and sixty-nine strains
      belonging to 17 common yeast species isolated from biological specimens were
      identified. Moreover, 13 strains belonging to seven species rarely isolated and
      not included in the Auxacolor data base were tested. Correct biochemical profiles
      were obtained with 95.2% of the strains from the first panel. These profiles
      alone permit correct identification of 62.7% of them (n = 106). The remainders
      (Candida glabrata, Candida krusei, Candida guilliermondii, Candida inconspicua
      and Candida lipolytica) require time consuming additional morphological
      observations for a definitive identification. However, the time needed to obtain
      the biochemical profiles of these 106 strains was shorter when using Auxacolor:
      77.4% of the strains were identified at 24 h with Auxacolor and 47.1% were
      identified at 24 h with ID 32C. Species from the second panel were not identified
      (seven strains) or incorrectly identified (six strains). The Auxacolor system was
      found to be reliable when performed in conjunction with morphological tests and
      easy to use for the identification of most medically important yeasts.

PMID- 7574111
TI  - [Validation of blood ethanol determination method by gas chromatography].

PMID- 7574112
TI  - A reply to: "Evaluation of methods for sodium, potassium, and chloride
      determination in relation to the analytical quality goals".

PMID- 7574110
TI  - Comparative activity of peroxidase-antibody conjugates with periodate and
      glutaraldehyde coupling according to an enzyme immunoassay.
AB  - Horseradish peroxidase is often used as an antibody-coupled enzyme and several
      procedures have been developed to obtain IgG-peroxidase conjugates. The most
      widely used are coupling with periodate or glutaraldehyde. To compare the
      efficiency of these methods, the authors conducted periodate coupling or
      glutaraldehyde coupling in one or two steps, using the same batches of
      peroxidase, C-reactive protein (CRP) and anti-CRP monoclonal antibodies to
      develop a specially sensitive Elisa for CRP. Comparison of immunoenzymatic
      activities showed that periodate-mediated conjugation was much more efficient,
      because the activity of the coupling products was about 100 times greater than
      that of the products obtained after one or two-step conjugation with
      glutaraldehyde. The lower coupling efficiency observed with glutaraldehyde was
      not due to inactivation of the coupling agent or to a possible decrease in the
      affinity of the conjugates for CRP due to the coupling procedure. The differences
      in efficiency can be ascribed to the fact that periodate induced more coupling
      sites than glutaraldehyde. Periodate is therefore a better coupling agent for
      preparing conjugates to be used in Elisa or related techniques, in which
      conjugate size does not hinder accessibility to the antigen.

PMID- 7574113
TI  - Proteases.
AB  - Proteases are enzymes which are widely distributed in cells and play a key role
      in protein metabolism. The aim of this paper is to review the classification and
      nomenclature of proteases, their catalytic mechanisms, the regulation of
      proteolytic activity and finally the major biological functions of proteases.

PMID- 7574114
TI  - [Serum determination of IgG, IgA, IgM, transferrin and haptoglobin. I. Attempt at
      normalization of results].
AB  - This study demonstrates the advantages and limitations of normalizing results for
      five serum proteins (IgG, IgA, IgM, transferrin and haptoglobin), analysed in
      liquid phase on ten different systems (open clinical chemistry and dedicated
      protein analysers). Seven sets of results from normal and pathological sera
      (without monoclonal proteins) were compared using: - calibrators supplied by each
      manufacturer; - - serial dilutions of a single stabilized pool of liquid serum.
      In addition to validating the quality of the stabilised serum, we have been able
      to identify: - significant variations in results using different analytical
      systems for the same sample; - a major reduction in these variations, often
      greater than 50%, through normalization using a common serum pool. In some two
      thirds of the cases, this reduction brought the degree of variation into an
      acceptable range.

PMID- 7574115
TI  - [Serum levels of IgG, IgA, IgM, transferrin and haptoglobin. II. Analytical
      precision and comparison of results from different analysers].
AB  - We compare the precision of immunochemical techniques for determining
      immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM),
      transferrin and haptoglobin. Precision was found satisfactory. Results of samples
      containing monoclonal Ig, showed substantial discrepancies, especially the serum
      containing monoclonal IgM. In this case, the nephelometric analysers gave the
      best results. In conclusion, when different techniques are used for monitoring
      protein immunoassays, a good knowledge of the performance of the analyser is
      necessary for correct interpretation and to avoid potentially misleading results.

PMID- 7574116
TI  - [Serum levels of IgG, IgA, IgM, transferrin and haptoglobin. III. Results
      obtained with monoclonal immunoglobulins].
AB  - This study is the third part of a multicenter evaluation carried out with ten
      analysers. Five proteins (IgG, IgA, IgM, transferrin, haptoglobin) were assayed
      in three sera, each containing one monoclonal Ig (IgG, IgA, or IgM). The expected
      agreement was not obtained with these particular sera, except in the case of
      haptoglobin. The marked imprecision of the monoclonal Ig quantification is
      highlighted, including the fact that many erroneous results are due to the
      antigen excess phenomenon. It is also shown that in the serum containing
      monoclonal IgM, quantification of the other proteins, remaining polyclonal Ig, as
      well as transferrin and haptoglobin, is difficult. The authors recall that
      electrophoresis and immunoelectrophoresis, which are indispensable for the
      characterization of the monoclonal components, are of great help in solving such
      difficulties.

PMID- 7574117
TI  - Simultaneous determination of itraconazole, hydroxy-itraconazole and amphotericin
      B in human plasma by HPLC with photodiode array detection.
AB  - A method for the fast analysis of itraconazole, hydroxy-itraconazole and
      amphotericin B is described which has the advantage of speed and specificity. The
      method is based on methanolic extraction of the compounds from plasma, followed
      by reverse-phase high-performance liquid chromatography with two detection
      wavelengths (263 and 405 nm). The extraction step provides > or = 94% recovery
      and the response of the detection system is linear from 50 to 5000 ng/ml. No
      other drugs have been found to interfere with the assay.

PMID- 7574118
TI  - Cardiobacterium hominis prosthetic valve endocarditis diagnosed in Portugal.

PMID- 7574119
TI  - [Guide to good practice of analysis in medical biology].

PMID- 7574120
TI  - Derivation of a decision rule for the use of radiography in acute knee injuries.
AB  - STUDY OBJECTIVE: To derive a highly sensitive decision rule for the selective use
      of radiography in acute knee injuries. DESIGN: Prospectively administered survey.
      SETTING: Emergency departments of two university hospitals. PARTICIPANTS:
      Convenience sample of 1,047 adults with acute knee injuries. RESULTS: Attending
      emergency physicians assessed each patient for 23 standardized clinical findings,
      which were recorded on data collection forms. A total of 127 patients was
      examined independently by two physicians to determine interobserver agreement.
      The outcome measure was fracture of the knee. Any patients who did not have ED
      radiography underwent a structured telephone interview to determine the
      possibility of a missed fracture. Those variables found to be both reliable
      (highest kappa values) and strongly associated with a fracture (highest chi 2
      values) were further analyzed by a recursive-partitioning multivariate technique.
      The derived decision rule included the following variables: (1) age 55 years or
      older, (2) tenderness at the head of the fibula, (3) isolated tenderness of the
      patella, (4) inability to flex to 90 degrees, and (5) inability to bear weight
      both immediately and in the ED (four steps). The presence of one or more of these
      findings would have identified the 68 fractures in the study population with a
      sensitivity of 1.0 (95% confidence interval [Cl], .95 to 1.0) and a specificity
      of .54 (95% Cl, .51 to .57). Application of the rule would have led to a 28.0%
      relative reduction in the use of radiography from 68.6% to 49.4% in the study
      population. CONCLUSION: A practical, highly sensitive, and reliable decision rule
      for the use of radiography in acute knee injuries has been derived. Clinical
      application should await prospective validation of the rule.

PMID- 7574121
TI  - Gender-associated differences in emergency department pain management.
AB  - STUDY OBJECTIVE: To determine whether patient or provider gender is associated
      with the number, type, and strength of medications received by emergency
      department patients with headache, neck pain, or back pain. DESIGN: Prospective
      cohort study. SETTING: Stanford University Hospital ED PARTICIPANTS: Patients 18
      years and older who arrived at the ED with a chief complaint of headache, neck
      pain, or back pain between February 1, 1993, and September 30, 1993. Provider
      participants included medical students, interns, residents, nurse practitioners,
      and attending physicians. RESULTS: ED administration of analgesic versus no
      analgesic, strength of analgesic administered, and administration of multiple
      medications. The study group consisted of 190 patients, 110 of them female. The
      patients were evaluated by 84 providers, 60 of them male. According to the
      providers surveyed, female patients described more pain than did male patients (P
      < .01) and were perceived by providers to experience more pain (P = .03). Female
      patients received more medications (P < .01) and were less likely to receive no
      medication (P = .01). Female patients also received more potent analgesics (P =
      .03). Linear and logistic regression analysis showed that patient perception of
      pain was the strongest predictor of the number and strength of medications given;
      patient gender was not a predictor. CONCLUSION: Female patients with headache,
      neck pain, or back pain describe more pain and are perceived by providers to have
      more pain than male patients in the ED. Female patients also receive more
      medications and stronger analgesics. In this study, severity of patient pain
      rather than gender stereotyping appeared to correlate most with pain-management
      practices.

PMID- 7574123
TI  - Clinical decision rules discriminate between fractures and nonfractures in acute
      isolated knee trauma.
AB  - STUDY OBJECTIVE: To develop criteria that optimize clinical decisionmaking in the
      use of radiography after isolated knee trauma in adults. DESIGN: A prospective
      survey of emergency department patients over a 7-month period. Standardized data
      forms were completed by emergency physicians, residents, and certified physician
      assistants. SETTING: A large suburban community teaching hospital. PARTICIPANTS:
      Two hundred forty-two patients older than 17 years with isolated knee injuries
      sustained less than 24 hours previously. RESULTS: We constructed a clinical
      decision model, calculating sensitivity, specificity, and odds ratios. Twenty
      eight patients (11.6%) had fractures, with the patella the most commonly
      fractured osseous structure. Patients able to walk without limping had not
      experienced a fracture, nor had patients with twist injuries without effusion.
      Sensitivity of this model for detecting fracture was 1.0 (99% confidence
      interval, .97 to 1.0), and specificity was .337 (99% confidence interval, .26 to
      .42). CONCLUSION: Clinical decision rules are effective in detecting knee
      fractures with 100% sensitivity and with sufficient specificity to eliminate 29%
      of knee radiographs in the ED. These findings require prospective validation.

PMID- 7574122
TI  - Cost-effectiveness analysis of the Ottawa Ankle Rules.
AB  - STUDY OBJECTIVE: To conduct an incremental cost-effectiveness analysis of
      implementation of the Ottawa Ankle Rules in emergency departments in the United
      States and Canada. DESIGN: A decision analytic approach to technology assessment.
      Clinical decision rules that allow physicians to be more selective in their use
      of radiography were compared with current practice in a decision analytic model.
      SETTING: A university hospital adult ED. PARTICIPANTS: ED physicians instructed
      in the use of the Ottawa Ankle Rules for adult patients with ankle injury.
      RESULTS: Radiography, waiting time, lost productivity, and medicolegal costs were
      calculated. In the United States, the savings varied between US$614,226 and
      US$3,145,910 per 100,000 patients, depending on the charge rate for radiography.
      In Ontario, Canada, the total savings were CAN$730,145 per 100,000 patients. One-
      and two-way sensitivity analyses that varied the rate of missed fractures, cost
      of radiography, probability of lawsuits, and cost of lawsuits did not change the
      results substantially. CONCLUSION: Implementation of the Ottawa Ankle Rules would
      result in significant savings of health care dollars despite the cost of missed
      fractures including litigation costs.

PMID- 7574125
TI  - Significance of scapular fracture in the blunt-trauma patient.
AB  - STUDY OBJECTIVE: To determine the significance of scapular fractures in blunt
      trauma patients compared with blunt-trauma patients without scapular fractures.
      DESIGN: Retrospective chart review of 11,500 blunt-trauma patients with a control
      group matched for age, sex, and mechanism of injury. SETTING: Two Level I trauma
      centers. PARTICIPANTS: Ninety-two blunt-trauma patients with scapular fractures
      and 81 control patients. RESULTS: Mortality, neurovascular injury, and injury
      severity scores were compared for blunt-trauma patients with scapular fractures
      with those of the control group. Analysis revealed a 1% incidence of scapular
      fractures in blunt trauma with no neurovascular injury and no mortality. Scapular
      fractures were associated with thoracic injury in 49% of the patients, compared
      with 6% in the control group (difference, 43%; 95% confidence interval, 31.6 to
      51.4; P < .001, Fisher's exact test). CONCLUSION: Scapular fractures are not a
      significant marker of greater mortality or of neurovascular morbidity in blunt
      trauma patients.

PMID- 7574124
TI  - Can a day 4 bone scan accurately determine the presence or absence of scaphoid
      fracture?
AB  - STUDY OBJECTIVE: To evaluate the accuracy of day 4 bone scans in predicting the
      presence or absence of fracture in patients with "clinical scaphoid fracture."
      DESIGN: Prospective sensitivity study of ED patients with clinical scaphoid
      fractures. Each patient was immobilized in a thumb spica cast and had day 4 bone
      scans of both wrists and hands. Blinded day 4 bone scan results were ultimately
      compared with the diagnosis on day 14 when patients returned for repeat clinical
      examination and radiographs. In cases of equivocal radiographic or clinical
      examination results, a day 14 bone scan was performed. SETTING: Two tertiary care
      teaching hospital emergency departments. PARTICIPANTS: All ED patients older than
      16 years with the diagnosis of clinical scaphoid fracture were eligible. RESULTS:
      Ninety-nine patients were enrolled and successfully completed the study protocol
      from October 1990 through November 1992. One patient had bilateral injury, for a
      total of 100 completed studies. Day 4 bone scans were 100% sensitive and 92%
      specific, for a positive predictive value of 65%, a negative predictive value of
      100%, and accuracy of 93% (95% confidence interval, 88%, to 98%). Many other
      types of fractures were identified on the day 4 scans, including those of the
      triquetra, distal radius, capitate, hamate, trapezoid, trapezium, and
      metacarpals. CONCLUSION: Day 4 bone scans are an accurate means of ruling out
      scaphoid fracture. However, because of a significant number of false-positive
      scans at day 4, they do not reliably confirm the diagnosis of scaphoid fracture.
      The bone scans also permitted identification of several other wrist fractures
      that had not been radiographically apparent.

PMID- 7574126
TI  - Simplification of emergency department discharge instructions improves patient
      comprehension.
AB  - STUDY OBJECTIVE: Emergency department patients have been shown to have difficulty
      understanding written discharge instructions. We attempted to determine whether
      improvements in comprehension can be achieved by simplification of available
      materials. DESIGN: We have previously tested patient understanding of standard
      discharge instructions. For this study, we simplified the standard instructions.
      Patients were given one of two simplified instruction sets. After reading the
      instructions, each patient was asked to answer five specific written questions
      about them. Results were compared with those from the original study. SETTING: ED
      of a large inner-city university hospital. PARTICIPANTS: Four hundred twenty
      three adult ED patients who presented on randomly selected days. RESULTS: The
      current and original groups were well matched for demographic variables. Each
      subject's responses were analyzed for overall success and for success with
      individual questions. The mean score for the current group was significantly
      improved over that of the original group. A trend toward improvement was
      demonstrated in all demographic groups with use of the simplified instructions.
      CONCLUSION: Simplified written materials may help patients who do not understand
      current standard materials. Health care providers should simplify written
      materials to make them understandable to the greatest number of patients.

PMID- 7574127
TI  - Occupational injury mortality in New Mexico.
AB  - STUDY OBJECTIVE: To examine specific risks for occupational injury deaths in New
      Mexico. DESIGN: Retrospective review of state medical investigator reports from
      1980 through 1991 with regard to industry, agent of death, gender, ethnicity,
      location, and alcohol and other drug involvement. PARTICIPANTS: New Mexico
      residents who were fatally injured while on the job. RESULTS: We identified 613
      deaths: 87.1% unintentional, 10.6% homicides, and 2.3% suicides. Industries with
      the most fatalities were construction (11.8%), oil/gas (10.6%), and farming
      (8.6%). The primary agents of death were motor vehicles (41.7%), firearms
      (10.1%), and falling objects (10.0%). Almost all (95.6%) of the decedents were
      male. However, females were overrepresented among homicide deaths (P < .0001).
      Most unintentional injuries occurred in rural areas (69.1%), whereas most
      homicides (73.4%) and suicides (71.4%) occurred in urban areas. Drug or alcohol
      use was evident in 19.4% of cases. CONCLUSION: New Mexico has a high rate of
      occupational injury death, which appears to be associated with rural location and
      use of motor vehicles and alcohol.

PMID- 7574128
TI  - Motorcycle trauma in the state of Illinois: analysis of the Illinois Department
      of Public Health Trauma Registry.
AB  - STUDY OBJECTIVE: To assess the current morbidity and mortality of motorcycle
      trauma in the state of Illinois and, specifically, to assess the incidence and
      cost of head injury to motorcycle crash patients according to their helmet use.
      DESIGN: Retrospective, cross-sectional examination of the Illinois Department of
      Public Health Trauma Registry, for which data are available from July 1, 1991,
      through December 31, 1992. Data are collected from all hospitals designated as
      Level I or Level II trauma centers in Illinois. PARTICIPANTS: All patients
      involved in motorcycle crashes and subsequently taken to a Level I or Level II
      trauma center in Illinois and entered into the trauma registry during the period
      studied. RESULTS: Head injury, spinal injury, helmet use, demographic data,
      hospital charges, days in ICU, and source of payment were selected as outcome
      measures. During the 18-month study period, 1,231 motorcycle trauma patients were
      entered into the trauma registry. Eighteen percent were helmeted and 56.0% were
      nonhelmeted. In 26.0% the helmet status at the time of the crash was unknown.
      Thirty percent of the helmeted patients sustained head injury and 4% sustained
      spinal or vertebral injury, compared with 51% and 8%, respectively, for
      nonhelmeted patients. Nonhelmeted patients were significantly more likely to
      sustain severe (Abbreviated Injury Score [AIS], 3 or more) or critical (AIS, 5 or
      more) head injury. Patients with these serious head injuries incurred almost
      three times the hospital charges and used a disproportionately larger share of
      ICU days than those with mild or no head injuries. There was a trend toward
      greater use of public funds or self-pay status (no insurance) for payment of
      hospital charges in nonhelmeted patients. CONCLUSION: Motorcycle helmet nonuse
      was associated with an increased incidence of serious head injury. Motorcycle
      trauma patients with severe or critical head injuries used a significantly
      greater proportion of ICU days and hospital charges than those with mild or no
      head injuries.

PMID- 7574129
TI  - Paramedic injury severity perception can aid trauma triage.
AB  - STUDY OBJECTIVE: To compare information contained in standard out-of-hospital
      trauma triage criteria and standard criteria plus advanced emergency medical
      technician (EMT) injury severity perception for determination of patient need for
      trauma center evaluation. DESIGN: Prospective, observational cohort analysis of
      trauma triage by advanced EMTs. PARTICIPANTS: Out-of-hospital, geographically
      stratified statewide sample of patients injured in Oregon. RESULTS: Advanced EMTs
      provided patient information on demographics, physiologic parameters, injury
      anatomy and mechanism, premorbid conditions, EMT injury severity perception, and
      trauma system entry status. A four-point scale was used to grade the injury
      severity perception. Need for trauma center evaluation was defined as major
      surgery within 6 hours of hospital arrival, admission to the ICU, death in the
      hospital, or Injury Severity Scale score of 16 or more. The relative triage
      information gain with injury severity perception was assessed by use of logistic
      regression, tree-based models, and receiver operating characteristic (ROC)
      curves. Of 1,063 patients, 307 (28.9%) warranted trauma center evaluation. With
      logistic regression modeling, the following standard triage parameters were
      associated (P < .05) with the need for trauma center evaluation after inclusion
      of injury severity perception: systolic blood pressure less than 90 mm Hg,
      abnormal respiratory rate (less than 10 or more than 29), Glasgow Coma Scale
      score less than 13, penetrating injury (midthigh to head), two or more obvious
      proximal long-bone fractures, and fall of more than 20 feet. The two largest
      injury severity perception categories had the greatest odds ratios (20:1 and
      167:1). ROC curve areas improved with injury severity perception (.88 versus .83
      without; P < .0001). CONCLUSION: Standard out-of-hospital triage criteria benefit
      from inclusion of advanced EMT injury severity perception information.

PMID- 7574130
TI  - Prospective, randomized trial of epinephrine, metaproterenol, and both in the
      prehospital treatment of asthma in the adult patient.
AB  - STUDY OBJECTIVE: To compare the effectiveness and incidence of adverse reactions
      with three treatment regimens for asthma in adults in the prehospital setting.
      DESIGN: Prospective, randomized clinical study. SETTING: Inner-city emergency
      medical service system providing basic and advanced life support and transport to
      14 urban area hospital emergency departments. PARTICIPANTS: One hundred fifty
      four adult asthmatic patients, 18 to 50 years old, who presented to paramedics
      with shortness of breath and wheezing. RESULTS: Eligible patients were randomly
      assigned by the base station physician to one of three treatment groups:
      subcutaneous epinephrine, nebulized metaproterenol, or subcutaneous epinephrine
      and nebulized metaproterenol. Peak expiratory flow rate (PEFR), blood pressure,
      heart rate, and respiratory rate were measured before and after treatment in each
      patient. During a 9-month period (October 1992 through June 1993), 154 patients
      were enrolled in the study; 53 (34%) received epinephrine, 49 (32%) received
      metaproterenol, and 52 (34%) received both. There were no significant differences
      in patient demographics, initial vital signs, or pretreatment PEFR among the
      three groups. The mean difference between pretreatment and posttreatment PEFR was
      73 L/min and did not significantly differ among the treatment groups. Significant
      changes in vital signs were seen in no treatment group. CONCLUSION: Nebulized
      metaproterenol is as effective as subcutaneous epinephrine in the prehospital
      treatment of adult patients with acute asthma. The combination of these two
      treatments offered no additional clinical benefit in the patients we studied.

PMID- 7574131
TI  - Upper-extremity impairment in young children.
AB  - STUDY OBJECTIVE: To determine the spectrum of disorders in children younger than
      6 years with upper-extremity injury or immobility and to identify clinical
      findings associated with specific disorders. DESIGN: Prospective patient series.
      SETTING: Urban pediatric emergency department. PARTICIPANTS: Children younger
      than 6 years seen during a 6-month period with injury or immobility of an upper
      extremity. RESULTS: We identified 178 episodes of immobility or injury of an
      upper extremity. Radial head subluxation (RHS) was the most frequent diagnosis
      (63%; 99 definite and 13 probable), followed by fracture (22%) and soft-tissue
      injury (STI; 13%). One patient each had humeral osteomyelitis and neurologic
      impairment. The mean age of children with RHS was significantly less than that of
      children with fractures (27 +/- 12 months versus 39 +/- 19 months, P < .01); the
      only diagnoses in children younger than 4 months old were infection and
      neurologic impairment. Multivariate regression analysis showed point tenderness
      and swelling correlated with fractures (P < .05). Decreased arm movement, absence
      of swelling, and a pull as the mechanism of injury correlated with RHS (P < .05).
      However, arm traction occurred in only 55% of the children with RHS (95%
      confidence interval = .46 to .64). By 1 week after the evaluation, all children
      without fractures had recovered, except one each with a sprain, osteomyelitis,
      and neurologic impairment. CONCLUSION: Most children with arm injury or
      immobility have bony or soft-tissue trauma, the majority being RHS. Clinical
      findings varied between diagnoses and may aid the clinician in deciding whether
      attempted reduction of RHS is indicated or whether radiographs are warranted
      first. Nontrauma diagnoses are unusual but should be considered, particularly in
      the child younger than 6 months old. Appropriate immobilization and follow-up are
      important for the management of children without a clear diagnosis at the initial
      evaluation.

PMID- 7574134
TI  - Emergency medicine: a Canadian perspective.

PMID- 7574132
TI  - Nebulized dexamethasone versus oral prednisone in the emergency treatment of
      asthmatic children.
AB  - STUDY OBJECTIVE: To compare nebulized dexamethasone with oral prednisone in the
      treatment of children with asthma. DESIGN: A randomized, double-blind, double
      placebo study. SETTING: An urban pediatric emergency department. PARTICIPANTS:
      Patients aged 1 to 17 years with acute asthma. INTERVENTIONS: Patients with
      moderate asthma exacerbation received frequent aerosolized albuterol and either
      1.5 mg/kg of nebulized dexamethasone or 2 mg/kg of oral prednisone. RESULTS: A
      total of 111 children was evaluated; 21% of those treated with dexamethasone
      required hospitalization, compared with 31% of those treated with prednisone (P =
      .26). A significantly greater proportion of dexamethasone-treated children were
      discharged home within 2 hours (23% versus 7%, P = .02). In the dexamethasone
      group, 8% who received the drug by mouthpiece were hospitalized compared with 33%
      who received it by face mask (P = .06). Fewer children treated with dexamethasone
      vomited (0% versus 15%, P = .001) and fewer relapsed within 48 hours of ED
      discharge (0% versus 16%, P = .008). CONCLUSION: Nebulized dexamethasone was as
      effective as oral prednisone in the ED treatment of moderately ill children with
      acute asthma and was associated with more rapid clinical improvement, more
      reliable drug delivery, and fewer relapses.

PMID- 7574133
TI  - Recommended guidelines for uniform reporting of pediatric advanced life support:
      the pediatric Utstein style.
AB  - This statement is the product of a task force meeting held June 8, 1994, in
      Washington DC in conjunction with the First International Conference on Pediatric
      Resuscitation and a follow-up task force writing group meeting held September 18,
      1994, in Chicago. Draft versions of the statement were circulated for comment to
      all members of the task force, the American Heart Association Subcommittee on
      Pediatric Resuscitation, and several outside reviewers. This statement and the
      International Conference on Pediatric Resuscitation were cosponsored by the
      American Academy of Pediatrics and the American Heart Association. The
      development of this statement was authorized by the American Academy of
      Pediatrics; the American Heart Association National Subcommittees on Pediatric
      Resuscitation, Basic Life Support, and Advanced Cardiac Life Support, the
      Committee on Emergency Cardiac Care, the Science Advisory Committee; and the
      European Resuscitation Council. In addition to the writing group, members of the
      Pediatric Utstein Task Force are Paul Anderson, M Douglas Baker, Jane Ball,
      Desmond Bohn, Dena Brownstein, J Michael Dean, Niranjan Kissoon, Bruce Klein,
      Patrick Malone, Karin McCloskey, James McCrory, P Pearl O'Rourke, Mary Patterson,
      Charles Schleien, James Seidel, Joseph J Tepas III, and Becky Yano.

PMID- 7574135
TI  - Infant involved in a motor vehicle accident.
AB  - The authors present and discuss the differential diagnosis for a 7-month-old
      infant who was seen in the ED after having been involved in a motor vehicle
      accident. The infant was subsequently found to have an odontoid fracture. Strict
      attention to the mechanism of injury is emphasized for appropriate evaluation of
      this patient's condition. An infant who becomes airborne in a car that is
      extensively damaged deserves an aggressive workup. In a child of this age,
      examination for subtle or even quite significant injury is difficult. Therefore
      the focus should be on the potential for injury. This article addresses the
      rarity of this injury pattern and discusses factors involved in treatment of
      cervical spine injuries in pediatric patients. The development of the axis and
      radiography of the cervical spine in pediatric patients are reviewed also.
      Neurosurgical treatment options are presented. This case also reminds us to
      ensure parents understand the proper use of a car seat.

PMID- 7574136
TI  - Avulsion fracture of the anterior superior iliac spine presenting as acute-onset
      meralgia paresthetica.
AB  - Avulsion fracture of the anterior superior iliac spine is rare. Most cases occur
      in adolescents involved in competitive sports or vigorous exercise in which the
      sartorius and tensor fascia lata muscles are contracted strongly and suddenly
      against a hyperextended trunk. Patients who sustain this injury usually
      experience acute pain in the anterior pelvic region. We describe a patient with
      avulsion of the anterior superior iliac spine who presented with meralgia
      paresthetica. The symptoms resolved with conservative treatment.

PMID- 7574137
TI  - Stress fracture of the hyoid bone caused by induced vomiting.
AB  - Fracture of the hyoid bone is a well-documented but rare consequence of certain
      types of trauma to the neck and lower face that may result in significant
      complications. We report a case of hyoid bone fracture, caused by induced
      vomiting, that resolved without complications and discuss the mechanism of injury
      and its complications, as well as associated injuries.

PMID- 7574138
TI  - Near-hanging caused by a toy necklace.
AB  - Hanging injuries and fatalities are rare among children and are usually
      unintentional. In this report we describe a 23-month-old girl who almost died
      when she accidentally hanged herself with a popular toy necklace, and we discuss
      recent epidemiological trends in accidental strangulations among children. This
      case emphasizes the need for increased awareness among consumers, health care
      providers, and product manufacturers about the dangers of toys such as the one
      described here.

PMID- 7574139
TI  - Chest pain and aortic dissection.

PMID- 7574140
TI  - Verification of tracheal tube placement.

PMID- 7574141
TI  - Urgent care clinics.

PMID- 7574142
TI  - Lightning injuries revisited.

PMID- 7574146
TI  - Managed care morbidity and mortality conference.

PMID- 7574143
TI  - No gag rule for intubation.

PMID- 7574144
TI  - Admission criteria for stroke.

PMID- 7574145
TI  - Admission criteria for stroke.

PMID- 7574147
TI  - Long-term follow-up of a severely hypothermic newborn.

PMID- 7574149
TI  - Comparison of the stride kinematics of the collected, medium, and extended walks
      in horses.
AB  - Six horses, highly trained for dressage competition, were used to study the
      stride kinematics of the walk, and to compare the kinematics of the collected,
      medium, and extended walks. Horses were filmed in a sagittal plane at a rate of
      150 frames/s; temporal, linear, and angular data were extracted from the films.
      Results of ANOVA and Duncan's multiple range test indicated that the speed of the
      collected walk (1.37 m/s) was significantly (P < 0.01) slower than that of the
      medium (1.73 m/s) and extended (1.82 m/s) walks, values for which were not
      significantly different from each other. The increase in speed was associated
      with a significant increase in stride length, from 157 cm in the collected walk
      to 193 cm in the extended walk. This was a result of an increase in the over
      tracking distance, whereas there was no significant difference in the distance
      between lateral placements of the limbs. Stride duration decreased (P < 0.01)
      from the collected walk (1,159 ms) to the extended walk (1,064 ms). Angles of the
      metacarpal and metatarsal segments, measured on the palmar/ plantar aspect, were
      higher at impact and lower at lift off in the collected than in the extended walk
      (P < 0.01). This indicated greater range of angular motion of this segment during
      the stance phase in the extended walk. Only 1 of the 6 horses had a regular 4
      beat rhythm of the footfalls, with equal time elapsing between the lateral and
      diagonal footfalls.

PMID- 7574148
TI  - Bacterial expression of the caprine arthritis-encephalitis virus gag and env
      proteins and their use in enzyme-linked immunosorbent assay.
AB  - The core protein and the transmembrane protein, encoded for the structural genes
      gag and env, respectively, of caprine arthritis-encephalitis virus were amplified
      by use of polymerase chain reaction, cloned into a pGEX-2T vector, and expressed
      in Escherichia coli as fusion proteins with the glutathione S-transferase at
      their C-terminus. The recombinant proteins were purified and evaluated by use of
      an ELISA. Sera from 269 goats were tested, and the results were compared with
      those obtained by use of immunoblot analysis. When results from both recombinant
      ELISA (r-ELISA) were compared, it appeared that the transmembrane glycoprotein
      was more immunoreactive than the core protein, because it was recognized by a
      higher percentage of sera from infected goats. When results of the 2 ELISA (p28 r
      ELISA and p40 r-ELISA) were combined in parallel, they were comparable to those
      of the immunoblot test, with sensitivity of 100% and specificity of 98.3%. It was
      also found that use of both r-ELISA makes it possible to compare the variable
      immunoreactivity against gag and env viral antigens, which may be correlated with
      the disease state. The r-ELISA, using core and transmembrane proteins, appears to
      be highly sensitive and specific for detection of antibodies against caprine
      arthritis-encephalitis virus.

PMID- 7574150
TI  - Characterization of iron status in young dogs with portosystemic shunt.
AB  - Microcytosis is a common laboratory finding in dogs with congenital portosystemic
      shunt (PSS), although its pathogenesis is not yet understood. Because the most
      common cause of microcytosis in dogs is absolute or relative iron deficiency,
      iron status was evaluated in 12 young dogs with PSS. Complete blood counting was
      done before surgical correction in all dogs, and in 5 dogs after surgery, by use
      of an automated hematology analyzer. Serum iron concentration and total iron
      binding capacity (TIBC) were determined coulometrically, and percentage of
      transferrin saturation was calculated. Erythrocyte protoporphyrin content was
      quantified by use of front-face fluorometry. Serum ferritin concentration was
      measured by use of ELISA. Serum ceruloplasmin content was determined
      colorimetrically (with p-phenylenediamine dihydrochloride as substrate) as an
      indirect indicator of subclinical inflammation, which may result in impaired iron
      utilization. Special stains were applied to liver (10 dogs; Gomori's) and bone
      marrow aspiration biopsy (7 dogs; Prussian blue) specimens for qualitative
      assessment of tissue iron content. Nonpaired Student's t-tests were used to
      compare serum iron concentration, TIBC, percentage of transferrin saturation, and
      erythrocyte protoporphyrin, ferritin, and ceruloplasmin concentrations in dogs
      with PSS with those in clinically normal dogs. All dogs had microcytosis before
      surgery; microcytosis resolved in 3 dogs after surgical correction. Serum iron
      concentration and TIBC were significantly lower in PSS-affected dogs than in
      clinically normal dogs. Erythrocyte protoporphyrin, ferritin, and ceruloplasmin
      concentrations in PSS-affected dogs were not significantly different from those
      in health dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574151
TI  - Urinary indices in llamas fed different diets.
AB  - Indices of renal function and damage were measured in 12 healthy male adult
      llamas fed a diet of mixed alfalfa/grass hay (mixed hay) and water ad libitum.
      Using a collection bag fitted over the preputial area, urine samples were
      collected at 6, 12, and 24 hours. Serum samples were obtained concurrently to
      determine endogenous creatinine clearance (CL), total (TE) and fractional
      excretion (FE) of electrolytes (Na, K, Cl, P), electrolyte CL, urine and serum
      osmolality, urine enzyme activities (gamma-glutamyltransferase and N-acetyl-beta
      D-glucosaminidase), and urine protein concentration. Urine production was
      quantified. Three months later, 10 of the 12 llamas were fed a grass hay diet and
      water ad libitum. Similar samples were obtained, and similar measurements were
      made. Urine production was higher when the llamas were fed the mixed hay diet.
      Total urine volume for llamas fed mixed hay ranged from 628 to 1,760 ml/24 h,
      with a median of 1,307.5 ml/24h, compared with a range of 620 to 1,380 ml/24 h
      and a median of 927.50 ml/24h for llamas fed grass hay. Median urine osmolality
      was higher in llamas fed mixed hay (1,906 mOsm/kg of body weight, with a range of
      1,237 to 2,529 mOsm/kg), compared with llamas fed grass hay (1,666 mOsm/kg with a
      range of 1,163 to 2,044 mOsm/kg). Creatinine CL did not vary significantly over
      time for either diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574153
TI  - Abortion in heifers inoculated with a thymidine kinase-negative recombinant of
      bovine herpesvirus 1.
AB  - The Copper isolate of bovine herpesvirus 1 (BHV-1) was used to produce a
      thymidine kinase-negative (TK-) recombinant by insertion of a beta-galactosidase
      (bgal) expression cassette into the TK coding region. The recombinant virus (TK-
      bgal+) was tested for abortifacient activity in cattle by inoculation of 5
      pregnant heifers at 25 to 29 weeks gestation. Five additional heifers were
      inoculated with the Cooper TK-positive (TK+) virus to serve as controls. After
      inoculation, both groups of heifers developed similar febrile responses and
      neutralizing antibody titers. Virus was isolated from blood of all heifers during
      the first postinoculation (PI) week, and isolation frequencies were similar for
      both groups. In contrast, whereas virus was isolated from many of the nasal and
      vaginal swab specimens of heifers inoculated with TK+ virus, only rare virus
      isolations were made from the heifers given TK- bgal+ virus. All heifers
      inoculated with TK+ virus aborted between PI days 19 and 35. The finding of
      characteristic microscopic lesions and viral antigen in fetal tissues indicated
      that the abortions were caused by BHV-1 infection. Virus was isolated from 3
      fetuses, and all isolates were TK+ virus. Two heifers inoculated with TK- bgal+
      virus aborted at PI days 25 and 39. Fetal tissues had typical BHV-1 microscopic
      lesions and viral antigen. Virus was isolated from blood of both fetuses, and the
      isolates were TK- bgal+. Results of this study indicate that inactivation of the
      TK gene reduces, but does not eliminate, the abortifacient activity of BHV-1.

PMID- 7574152
TI  - Colonization of the tonsils and nasopharynx of calves by a rifampicin-resistant
      Pasteurella haemolytica and its inhibition by vaccination.
AB  - A rifampicin-resistant Pasteurella haemolytica serotype 1 with 2 added plasmids
      was used as a colonization-challenge strain in calves to test the resistance to
      colonization elicited by vaccination. Nine calves were vaccinated with a tissue
      culture-derived P haemolytica serotype-1 vaccine which, in a prior study, had
      elicited a serotype-specific inhibition of nasal and tonsillar colonization by
      the homologous serotype under field conditions. The vaccinates and 9
      nonvaccinated control calves were exposed by tonsillar instillation with the
      challenge strain. The P haemolytica were enumerated in nasal secretion and tonsil
      wash specimens collected biweekly for 3 weeks. Rifampicin-supplemented agar
      medium inhibited growth of other bacterial species in the specimens and, thus,
      increased the sensitivity of detection of the challenge P haemolytica by 100
      fold. The challenge strain retained its plasmids during the period of
      colonization. Inhibition of colonization was evidenced by lower frequency of
      isolations and fewer isolations of the challenge strain from nasal secretion and
      tonsil wash specimens of the vaccinates than from those of the nonvaccinates.

PMID- 7574155
TI  - Microorganisms isolated from the corneal surface before and during topical
      cyclosporine treatment in dogs with keratoconjunctivitis sicca.
AB  - The effect that topical administration of cyclosporine would have on the number
      and type of microorganisms isolated from the corneal surface of dogs with
      keratoconjunctivitis sicca was studied. Schirmer tear test wear performed on and
      corneal swab specimens were collected from 61 eyes of 31 dogs with
      keratoconjunctivitis sicca prior to and after 3, 6, and 12 months of treatment
      with cyclosporine. In eyes that responded to cyclosporine treatment (Schirmer
      tear test value increased by > or = 5 mm/min, compared with pretreatment value),
      the percentage of eyes from which bacteria were isolated 3, 6, and 12 months of
      treatment was significantly (P < 0.001) less than the percentage from which
      bacteria were isolated prior to treatment. However, among eyes that did not
      respond to treatment, we did not detect a significant change over time in
      prevalence of bacteria or type of bacteria isolated. The percentage of eyes from
      which fungi were isolated decreased during treatment; however, the small number
      of eyes in which fungal culture results were initially positive precluded
      demonstration of a significant differences over time in the frequency with which
      specific bacterial genera were isolated, with the exception of beta-hemolytic
      Streptococcus spp. Opportunistic corneal infections were not detected even though
      none of the dogs received antibiotics. An increase in production of tears, which
      contain anti-infection, proteins, was believed to be the primary factor
      responsible for the decrease in the percentage of eyes from which microorganisms
      could be isolated.

PMID- 7574154
TI  - Vaccination of cattle with outer membrane protein-enriched fractions of
      Pasteurella haemolytica and resistance against experimental challenge exposure.
AB  - Administration of an N-lauroylsarcosine-derived outer membrane protein fraction
      of Pasteurella haemolytica A1 (SCI-1) induced a protective response in calves
      against intrathoracic challenge exposure with the homologous serovar. Outer
      membrane proteins from heterologous serovars, A6 and A9, induced partial
      protection that was associated with their respective similarities to serovar A1
      in outer membrane protein profiles derived by use of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Calves vaccinated with SCI preparations did
      not have detectable neutralizing antibody to P haemolytica A1 leukotoxin.
      Antibodies to whole-cell antigens, carbohydrate-protein subunit antigen, and SCI
      1 were associated with resistance, which indicates that protein antigens shared
      among cell surface, carbohydrate-protein subunit, and SCI preparations are
      immunogenic and enhance resistance to experimental challenge exposure.

PMID- 7574156
TI  - Evaluation of health and ruminal variables during adaptation to grain-based diets
      in beef cattle.
AB  - Health and ruminal variables were intensively measured during adaptation to grain
      based diets in 6 beef cattle with fistulated rumens. The cows had been maintained
      on prairie grass hay-supplemented diets, and were converted to a grain-based
      finishing ration by feeding each successive diet (diets 1-4, respectively) for a
      period of 7 days. Each cow was evaluated and samples were obtained 3 times each
      day for the first 5 days that each diet was fed. Health variables monitored were
      rectal temperature, pulse, respiratory and rumen motility rates, fecal
      consistency, demeanor, blood pH, and blood glucose and L (+) lactate
      concentrations. Ruminal variables monitored were pH and glucose, DL-lactate, and
      volatile fatty acid concentrations of rumen contents. Data were analyzed by use
      of a multivariate ANOVA. We determined that most of the health variables were
      within reference range limits throughout the adaptation period; however, analysis
      of pulse and respiratory rates indicated that diets 2 and 4 were stressful.
      Although blood pH continually decreased during feeding of the 4 diets (7.38 to
      7.30), blood L (+) lactate and glucose concentrations had large increases only
      within diet 4. The pH of ruminal contents decreased progressively from 6.8 to
      5.3. Rumen glucose concentration was low (< mumol/ml), except with diet 4 in
      which values were 8 times higher than for other diets. By the end of the study,
      the ruminal contents of all animals were acidic (pH < 5.5), and, on the basis of
      higher than background amounts of ruminal glucose and DL-lactate, it was
      determined that rumen microbial equilibrium had not yet been achieved.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7574157
TI  - Influence of two amounts of dietary casein on uric acid, sodium urate, and
      ammonium urate urinary activity product ratios of healthy beagles.
AB  - Casein has been used as a protein source in diets designed to dissolve canine
      ammonium urate uroliths and to prevent their recurrence, because it contains
      fewer purine precursors than do many other sources of protein. However, an
      important question is whether reduced quantities of dietary casein have any
      benefit in modifying saturation of urine with urates. To answer this question,
      activity product ratios of uric acid, sodium urate, and ammonium urate were
      determined in 24-hour urine samples produced by 6 healthy Beagles during periods
      of consumption of a 10.4% protein, casein-based (10.4% casein) diet and a 20.8%
      protein, casein-based (20.8%casein) diet. Significantly lower 24-hour urinary
      excretions of ammonia and phosphorus were observed when dogs consumed the 10.4%
      casein diet. These results suggest that use of the 10.4% casein diet in protocols
      designed for dissolution and prevention of uric acid, sodium urate, and ammonium
      urate uroliths in dogs may be beneficial.

PMID- 7574160
TI  - Effect of sodium hexametaphosphate on dental calculus formation in dogs.
AB  - A series of studies was conducted to identify a practical measure for preventing
      dental calculus formation in dogs. The studies involved a colony of 27 Beagles
      that received an initial dental prophylaxis. The dogs were then stratified on the
      basis of their normal rate of calculus formation and randomly assigned to
      parallel groups within each strata. During 4-week test periods, a variety of
      experimental regimens were instituted, followed by clinical assessments of
      calculus. Major observations were that a crystal growth inhibitor, soluble
      pyrophosphate, incorporated into a dry dog food modestly reduced calculus
      formation when used at high concentration; anticalculus effects attributable to
      this agent were significant (P < 0.05) only when it was used as a surface
      coating; the coating of dry dog chow or plain biscuits with a calcium
      sequestrant, sodium hexametaphosphate (HMP), provided the greatest benefit and
      resulted in significant (P < 0.05) reductions in calculus formation of about 60
      to 80%, depending on the dosage regimen; and the feeding of a single daily snack
      of 2 HMP-coated plain biscuits (0.6% HMP) decreased calculus formation by nearly
      80%. We concluded that the coating of dry dog chow or plain dog biscuits with HMP
      is an effective means of reducing calculus formation in dogs.

PMID- 7574158
TI  - Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs.
AB  - Dogs are particularly susceptible to development of glucocorticoid-induced
      hepatopathy, but the mechanisms are not well understood. We investigated the
      pathogenesis of glucocorticoid hepatopathy by examining sequential morphologic
      and biochemical changes in the liver of dogs during steroid administration. Six
      adult Beagles were given prednisolone acetate (4mg/kg of body weight, once daily
      for 24 days IM). Serum samples and percutaneous liver biopsy specimens were
      obtained before the start of the study (treatment day [TD] 0) and at TD 5, 10,
      15, and 25. There were significant (P < 0.05) and progressive increases in serum
      activities of alkaline phosphatase, gamma-glutamyltransferase, and alanine
      transaminase. Light microscopic changes in liver biopsy specimens included
      progressive hepatocellular swelling and vacuolation. Electron microscopy revealed
      glycogen accumulation, peripheral displacement of organelles, and prominent
      dilatation of bile canaliculi, compared with findings at TD 0. Liver biopsy
      specimens taken at TD 25 had significantly (P < 0.05) increased activities of the
      plasma membrane enzymes, alkaline phosphatase and gamma-glutamyltransferase, and
      5'-nucleotidase was significantly (P < 0.001) decreased. Subcellular
      fractionation on reorientating sucrose density gradients revealed high-density
      peaks of alkaline phosphatase and gamma-glutamyltransferase, compatible with a
      specific increase in the biliary canalicular component of the enzyme activities.
      Neutral alpha-glucosidase activity was shifted to the denser fractions,
      indicative of an increase in the proportion of rough to smooth endoplasmic
      reticulum and consistent with enhanced synthesis of plasma membrane proteins.
      There also was evidence for progressive increase in fragility of intracellular
      organelles, particularly lysosomes. These findings indicate that glucocorticoid
      hepatopathy in dogs is associated with progressive alterations not only to the
      plasma membrane, but also to other subcellular organelles.

PMID- 7574159
TI  - Effects of furosemide, exercise, and atropine on tracheal mucus transport rate in
      horses.
AB  - Effects of furosemide, exercise, and atropine on tracheal mucus transport rate
      (TMTR) in horses were investigated. Atropine (0.02 mg/kg of body weight)
      administered IV or by aerosolization significantly (P < 0.05) decreased TMTR at
      60, but not at 30 minutes after its administration in standing horses. Furosemide
      (1.10 mg/kg, IV) did not have any significant effect on TMTR when measured at 2
      or 4 hours after its administration in standing horses. Exercise alone or
      furosemide (1.10 mg/kg, IV) administration followed 4 hours later by exercise did
      not alter TMTR, compared with values for standing control or exercised horses
      administered saline solution. Atropine (0.02 mg/kg, IV) administered after
      exercise significantly (P < 0.05) decreased TMTR, compared with values for no
      exercise standing controls, for exercise after administration of saline solution,
      and for furosemide and exercise.

PMID- 7574161
TI  - Urethral pressure response to smooth and skeletal muscle relaxants in
      anesthetized, adult male cats with naturally acquired urethral obstruction.
AB  - The effects of the skeletal muscle-relaxing drug dantrolene sodium alone, and in
      combination with the alpha 1-adrenergic antagonist prazosin, on the urethral
      pressure profile were investigated in male cats with obstructive lower urinary
      tract disease. Decreases in mean segmental intraurethral pressure induced by
      dantrolene (n = 3) or dantrolene in combination with prazosin (n = 3) were
      evaluated statistically, using a paired design. Statistical analysis was applied
      to absolute (mm of Hg) pressure values. Intravenous administration of dantrolene
      alone (1 mg/kg of body weight, n = 3) significantly decreased pressure in the
      postprostatic/penile urethral segment, but did not decrease prostatic urethral
      pressures. Dantrolene in combination with prazosin (0.03 mg/kg IV) caused a 20%
      pressure decrease in the prostatic segment (P = 0.060). Preprostatic urethral
      pressure was not significantly affected by either treatment regimen in the small
      pool of cats studied. There was no difference in baseline pressures (mm of Hg) in
      the 3 intraurethral segments of these 6 recently obstructed male cats, compared
      with historic baseline pressures (mm of Hg) in the 3 intraurethral segments of 28
      healthy male cats. These results indicate that dantrolene and prazosin may be
      effective in relaxing intraurethral skeletal and smooth musculature in male cats
      clinically afflicted with obstructive lower urinary tract disease. However, it is
      not certain that administration of muscle relaxants would facilitate urethral
      catheterization and removal of the obstruction in male cats with blockage of the
      lower urinary tract. Strikingly, results of this study suggest that urethral
      muscle spasm had a minor role in these cats.

PMID- 7574162
TI  - Partitioning of total pulmonary resistance in horses.
AB  - The partitioning of total pulmonary resistance (RL) into upper airway resistance
      and lower airway resistance (RI) was studied in 8 Thoroughbred geldings. In
      addition, the phase shift and amplitude distortion of 3 catheters used for
      pressure measurements in this study were evaluated under static and dynamic
      conditions. Flow rate was obtained from a heated pneumotachograph attached to a
      tight-fitting mask placed over the nose. Electronic integration of the flow
      signal gave tidal volume. Transpulmonary pressure (PL) was obtained from
      calculation of the difference between the esophageal balloon catheter pressure
      and mask pressure. Lateral tracheal pressure was measured from a polyethylene
      catheter placed percutaneously in the middle portion of the trachea. Lower airway
      pressure (PI) was calculated as the difference between esophageal pressure and
      lateral tracheal pressure. Similarly, upper airway pressure was defined as the
      difference between lateral tracheal pressure and mask pressure. Pressures are
      reported as the difference between the maximal and the minimal pressures recorded
      during a respiratory cycle. Airway resistance was calculated, using the isovolume
      method, at 50% of tidal volume. There were individual and group variations in Pi
      and Pl/PL, although Pi accounted for more than 60% of PL in all horses. In 6
      horses, Rl was more than 50% of RL whereas in 2 horses, Rl was only 30 and 34% of
      RL. Amplitude distortion was minimal for the 3 catheters under static conditions
      in the in vitro study. Under dynamic conditions, amplitude distortion varied
      according to the catheter studied, the frequency, and the resistance of the
      system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574163
TI  - Effects of alpha 2-adrenergic receptor agonist and antagonist drugs on
      cholinergic contraction in bovine tracheal smooth muscle in vitro.
AB  - Effects of alpha 2-adrenergic receptor stimulation on the cholinergic contractile
      response of bovine tracheal smooth muscle were studied. To determine the presence
      and function of alpha2-adrenergic receptors on cholinergic nerves innervating
      bovine tracheal muscle, effects of 2 alpha 2-adrenoceptor agonists and an
      antagonist were determined. Muscular contractions were elicited by either
      electrical field stimulation (EFS) or exogenous acetylcholine (ACH). The
      contractile response to EFS and exogenous ACH was examined for each tissue.
      Electrical field stimulation of bovine tracheal smooth muscle caused contractions
      that were completely abolished by atropine, indicating that predominant
      excitatory innervation of bovine trachea is cholinergic. The alpha 2
      adrenoreceptor agonists clonidine and medetomidine (10(-6) M to 10 (-4) M)
      concentration-dependently inhibited the contractile response to EFS but not the
      response to exogenous ACH. Contractions induced by EFS were significantly (P <
      0.05) inhibited in clonidine (10(-4) M) - treated tissues at low frequencies
      (0.01 to 10 Hz), whereas medetomidine (10(-5) M, 10(-4) M) inhibitory effects of
      the alpha 2-adrenoreceptor agonists clonidine and medetomidine were attenuated by
      the a2-adrenoreceptor antagonist tolazoline. The alpha 2-agonists used in this
      study appear to cause prejunctional inhibition of cholinergic nerves, because the
      smooth muscle contractions elicited by EFS, but not exogenous ACH, were
      inhibited, compared with controls.

PMID- 7574164
TI  - Effects of topically applied mitomycin-C on intraocular pressure, facility of
      outflow, and fibrosis after glaucoma filtration surgery in clinically normal
      dogs.
AB  - The effects of mitomycin-C on intraocular pressure (IOP), facility of outflow
      (C), and Tenon's capsule fibrosis were studied over 60 days in 10 clinically
      normal dogs. A-1-piece, silicone glaucoma implant was surgically implanted into
      both eyes; the filtration site of one eye was treated with a single, 5-minute
      intraoperative application of mitomycin (0.5 mg/ml), and the fellow eye was
      treated in a similar manner with balanced salt solution. There were no
      significant differences in preoperative IOP or C-values between treatment groups.
      Mean IOP in eyes of both groups initially decreased from the preoperative value,
      but returned to the baseline value by day 21. Mean facility of aqueous outflow (C
      value) increased in all eyes during the first 14 days (mitomycin-C-value = 2.26
      +/- 0.72; control C-value = 2.38 +/- 0.81), then reached a plateau that was
      significantly higher than the baseline value in mitomycin (P = 0.039) and control
      (P = 0.041) eyes. Histologic evaluation revealed all implants surrounded by a
      connective tissue capsule composed of regular dense collagen and fibroblasts that
      was significantly (P = 0.003) thinner in the mitomycin-treated (scleral side =
      167 +/- 62 microns; conjunctival side = 122 +/- 41 microns) than the control
      (scleral side = 261 +/- 92 microns; conjunctival side = 180 +/- 48 microns)
      group. There were, however, no significant differences in IOP or C-values between
      groups at any postoperative time interval. Results of this study indicate that
      intraoperative treatment with mitomycin suppresses, but does not prevent fibrosis
      around silicone filtering implants.

PMID- 7574165
TI  - Effects of three occlusive dressing materials on healing of full-thickness skin
      wounds in dogs.
AB  - The effects of 3 occlusive dressing materials and a standard, nonadherent
      dressing material on healing of full-thickness skin defects were evaluated in
      dogs. Two wounds measuring 2 x 2 cm were created bilaterally (4 wounds/dog) on
      the dorsolateral aspect of the trunk of 12 Beagles. Wound treatments were evenly
      distributed between 4 sites, using a Latin square design. Treatments evaluated
      were: equine amnion (group A), biosynthetic hydrogel dressing (group B),
      transparent polyethylene sheeting (group T), and a semi-occlusive
      rayon/polyethylene, nonadherent dressing (group C). Rates of contraction and
      epithelialization of group-A wounds were significantly greater than those of
      wounds of groups C, B, and T. On days 14, 21, and 28, mean percentage of wound
      contraction and mean percentage of total wound healed in group A exceeded those
      wounds in groups C, B, and T. On day 28, wounds in group A were significantly
      smaller than wounds in groups B and T, but were not significantly smaller than
      wounds in group C. All wounds in group A achieved 100% healing during the 28-day
      study period. Mean time for complete healing of group-A wounds was 21 days. The
      percentages of wounds completely healed by day 28 for groups B, C, and T were 25,
      67, and 25%, respectively. Results indicate that use of equine amnion as an
      occlusive biological dressing on full-thickness wounds in dogs increases rate of
      healing.

PMID- 7574166
TI  - Effect of the neodymium:yttrium aluminum garnet laser on postoperative neuroma
      formation after neurectomy in rats.
AB  - The effect of neodymium:yttrium aluminum garnet (Nd:YAG) laser-performed
      neurectomy was compared with conventional scalpel-performed neurectomy, using the
      rat sciatic nerve model. Sixteen male Sprague-Dawley rats underwent unilateral
      transection of the sciatic nerve by 1 of 3 methods. The sciatic nerve of rats
      under general anesthesia was transected by use of a steel scalpel blade (group 1,
      n = 5); a contact Nd:YAG laser at 6W of power (group 2, n = 6); or an Nd:YAG
      laser at 12 W of power (group 3, n = 5). Thirty days after surgery, all rats were
      euthanatized and the nerves were harvested, imbedded in paraffin, fixed, and
      sectioned for light microscopy. Neurodegenerative changes and perineurial cell
      proliferation were least severe in the nerves transected by use of a steel
      scalpel (group 1), and were most severe in nerves transected by use of laser at 6
      W of power (group 2). There was a significant difference in prevalence of
      perineurial proliferation between the scalpel and laser neurectomy groups (P =
      0.029). There was no significant difference in prevalence of neuroma formation or
      neurodegeneration between the laser and scalpel neurectomy groups, although
      neuromas were found in 3 rats (2 from group 2 and 1 from group 3). Within the
      limits of this study, we found that the Nd:YAG laser was less successful than
      sharp division, using a scalpel, in preventing neuroma formation after nerve
      transection.

PMID- 7574169
TI  - 'High-touch' versus 'high-tech'. Can the caring profession survive in a health
      care system being driven by technology?

PMID- 7574167
TI  - Effects of long-term zearalenone administration on spermatogenesis and serum
      luteinizing hormone, follicle-stimulating hormone, and prolactin values in male
      rats.
AB  - Body and testis weights, serum luteinizing hormone, follicle-stimulating hormone,
      and prolactin values and volume fractions of Sertoli cells, spermatogonia, early
      and late primary spermatocytes, and round and long spermatids were evaluated in
      70-day-old male rates treated orally with 20 mg of zearalenone/kg of body weight
      daily for 5 weeks. Significant (P < 0.05) increase in serum prolactin
      concentration was consistently observed during the 5 weeks of treatment with
      zearalenone. Significant changes were not observed in any of the other variables
      evaluated.

PMID- 7574168
TI  - Complete primary sequence of equine cartilage link protein deduced from
      complementary DNA.
AB  - Investigation of the structure of the equine articular cartilage link protein
      (LP) from individuals ranging in age from 1 to 15 years identified 3 distinct
      isoforms having molecular weights of 46,000, 43,000 and 41,000. The relative
      amounts of each of the 3 isoforms altered with age. The largest form did not
      change with age; however, amounts of the Mr 43,000 and 41,000 forms increased
      with increasing age. The results suggested that an accumulation, in the
      extracellular matrix of cartilage, of these 2 smaller products may have arisen
      from proteolytic cleavage. The complete amino acid sequence of the protein core
      was determined from complementary DNA products prepared by polymerase chain
      reaction amplification of cartilage LP mRNA. The sequence had 96% similarity with
      human LP and with that of other species for which the primary structure has been
      determined. This high degree of sequence conservation and the isoform data
      indicate that extracellular processing of LP occurs by similar mechanisms in
      various species. At the transcription level, equine chondrocytes were found to
      express LP as 2 abundant mRNA of 5.0 and 3.0 kb, and a smaller mRNA of 1.5 kb.
      Processing of the LP m RNA in horses, thus, appears to be similar to that found
      in other species investigated, an although multiple transcripts are present, the
      coding region remains unaltered and only 1 protein product is made.

PMID- 7574171
TI  - Telehealth, telenursing, telewhat?

PMID- 7574170
TI  - CNA leaders propose bylaws changes, plan to leave ANA.

PMID- 7574172
TI  - ENA survey examines facets of workplace violence.

PMID- 7574173
TI  - Staff nurse caucus attracts unprecedented crowd, begins planning for 1996.

PMID- 7574174
TI  - ANA responds to CNA's proposal for separate code of ethics.

PMID- 7574176
TI  - Pretty scary staff. As I see it.

PMID- 7574175
TI  - End of summer brings mixed emotions.

PMID- 7574177
TI  - Caring for the caregivers. MNA leads the fight to protect RNs from dangerous air
      quality at work sites.

PMID- 7574178
TI  - PEW efforts seek to change how health professions are regulated.

PMID- 7574180
TI  - SNAs successful in protecting, enhancing advanced practice nursing.

PMID- 7574179
TI  - ANA introduces 'survival kit' in face of massive hospital restructuring.

PMID- 7574181
TI  - ANA acts to end 'pediatric epidemic' of smoking.

PMID- 7574182
TI  - ANA supports Clinton's efforts to curb tobacco use by youths.

PMID- 7574183
TI  - ANA: a family of nurses devoted to the profession.

PMID- 7574184
TI  - ANA: building on a proud history of fighting for nursing practice: key to patient
      care safety, quality.

PMID- 7574185
TI  - ANA's commitment to nurses and patients: a chronology.

PMID- 7574186
TI  - ANA: building on a proud history of fighting for nursing practice.

PMID- 7574187
TI  - Firearm deaths among children and youth.
AB  - Nationally, homicide and suicide are the 2nd and 3rd leading causes of death
      among children and youth under the age of 21. Sixteen to 19-year-olds now have
      the highest rate of handgun victimization among all age groups. The firearm
      suicide rate for White males is over 4 times higher than the rate for African
      American males, whereas the firearm homicide rate is over 9 times higher for
      African American males. Almost half of all deaths among African American male
      teenagers now involve firearms. Multiple steps, both short- and long-term, need
      to be taken to reduce firearm death rates among children and youth. Some of the
      possible methods to do so are discussed.

PMID- 7574188
TI  - Violent juvenile delinquents. Treatment effectiveness and implications for future
      action.
AB  - Traditionally, the juvenile justice system has emphasized the goals of treatment
      and rehabilitation of young offenders, while protecting them from punishment,
      retribution, and stigmatization. Violent juvenile offenders have posed a
      challenge to this rehabilitative ideal because of mounting public pressure to
      ensure societal protection. Juveniles who are perceived as dangerous or
      persistent in their criminal activity are increasingly transferred to the adult
      criminal justice system, where they may receive much harsher consequences.
      Whether violent delinquents can be successfully treated is a key point in the
      debate regarding the wisdom of this trend in juvenile justice. This article
      considers the available research to address the policy question of how society
      should reasonably invest in the treatment of violent juvenile offenders.

PMID- 7574189
TI  - The effects of exposure to violence on young children.
AB  - Violence has been characterized as a "public health epidemic" in the United
      States. At the same time, children's witnessing of violence is frequently
      overlooked by law enforcement officers, families, and others at the time of a
      violent incident. Although mothers describe the panic and fear in their children
      and themselves when violence occurs, little research or clinical attention has
      focused on the potential impact on children of living under conditions of chronic
      community violence. The purpose of this article is to present an overview of
      available research and clinical understanding of the effects of exposure to
      violence on school-age and younger children. Suggestions for future research and
      public policy initiatives are offered.

PMID- 7574190
TI  - Child maltreatment research. Federal support and policy issues.
AB  - The recent history of federal support for child maltreatment research paints a
      mixed picture of inadequate funding and uncertain administrative guidance against
      a backdrop of growing public concern about the prevalence of child abuse and
      neglect. This article describes some of the problems that have been identified in
      federal research funding, administration, and support of research initiatives and
      training concerning child abuse and neglect. Remedies for these difficulties are
      outlined, priorities for new research in this area are identified, and ways in
      which to rejuvenate the federal government's role in this area, in league with a
      concerted commitment to policy-relevant research by behavioral scientists, are
      suggested.

PMID- 7574191
TI  - The "battering syndrome": prevalence and clinical characteristics of domestic
      violence in primary care internal medicine practices.
AB  - OBJECTIVES: To determine the prevalence of domestic violence among female
      patients and to identify clinical characteristics that are associated with
      current domestic violence. DESIGN: Cross-sectional, self-administered, anonymous
      survey. SETTING: 4 community-based, primary care internal medicine practices.
      PATIENTS: 1952 female patients of varied age and marital, educational, and
      economic status who were seen from February to July 1993. MEASUREMENTS: The
      survey instrument included previously validated questions on physical and sexual
      abuse, alcohol abuse, and emotional status and questions on demographic
      characteristics, physical symptoms, use of street drugs and prescribed
      medications, and medical and psychiatric history. RESULTS: 108 of the 1952
      respondents (5.5%) had experienced domestic violence in the year before
      presentation. Four hundred eighteen (21.4%) had experienced domestic violence
      sometime in their adult lives, 429 (22.0%) before age 18 years, and 639 (32.7%)
      as either an adult or child. Compared with women who had not recently experienced
      domestic violence, currently abused patients were more likely to be younger than
      35 years of age (prevalence ratio [PR], 4.1 [95% CI, 2.8 to 6.0]); were more
      likely to be single, separated, or divorced (PR, 2.5 [CI, 1.7 to 3.6]); were more
      likely to be receiving medical assistance or to have no insurance (PR, 4.3 [CI,
      2.8 to 6.6]); had more physical symptoms (mean, 7.3 +/- 0.38 compared with 4.6 +/
      0.08; P < 0.001); had higher scores on instruments for depression, anxiety,
      somatization, and interpersonal sensitivity (low self-esteem) (P < 0.001); were
      more likely to have a partner abusing drugs or alcohol (PR, 6.3 [CI, 4.4 to
      9.2]); were more likely to be abusing drugs (PR, 4.4 [CI, 1.9 to 10.4]) or
      alcohol (PR, 3.1 [CI, 1.5 to 6.5]); and were more likely to have attempted
      suicide (PR, 4.3 [CI, 2.8 to 6.5]). They visited the emergency department more
      frequently (PR, 1.7 [CI, 1.2 to 2.5]) but did not have more hospitalizations for
      psychiatric disorders. In a logistic regression model into which 9 risk factors
      were entered, the likelihood of current abuse increased with the number of risk
      factors, from 1.2% when 0 to 1 risk factors were present to 70.4% when 6 to 7
      risk factors were present. CONCLUSIONS: In a large, diverse, community-based
      population of primary care patients, 1 of every 20 women had experienced domestic
      violence in the previous year; 1 of every 5 had experienced violence in their
      adult life; and 1 of every 3 had experienced violence as either a child or an
      adult. Current domestic violence is associated with single or separated status,
      socioeconomic status, substance abuse, specific psychological symptoms, specific
      physical symptoms, and the total number of physical symptoms.

PMID- 7574192
TI  - Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous
      and arterial occlusive disease.
AB  - OBJECTIVE: To evaluate the prevalence of moderate hyperhomocysteinemia and
      inherited thrombophilia disorders (congenital defects of the natural
      anticoagulant or fibrinolytic mechanisms) in patients with early-onset venous or
      arterial thromboembolic disease. DESIGN: Cross-sectional 2-year evaluation of
      consecutive unrelated patients with a history of venous or arterial occlusive
      disease occurring before the age of 45 years or at unusual sites, in the absence
      of local predisposing factors. SETTING: Thrombosis research unit of a community
      hospital. PATIENTS: 107 patients with venous thromboembolism (mean age at event,
      32.9 +/- 11.9 years) and 50 patients with arterial occlusive disease (mean age at
      event, 31.1 +/- 10 years) who did not have acquired coagulation defects, overt
      cancer, or acquired conditions affecting methionine metabolism. MEASUREMENTS:
      Total plasma homocysteine (fasting levels), antithrombin III, protein C, protein
      S, activated protein C resistance, plasminogen, and heparin cofactor II were
      measured at least 3 months after the event. In 87 patients, total plasma
      homocysteine levels were also measured 8 hours after an oral methionine load was
      administered (L-methionine, 0.1 g/kg body weight). Ninety-fifth percentiles of
      the distribution of these variables were established in 60 apparently healthy
      persons; sex-specific ranges were used for protein S and total plasma
      homocysteine. Relatives of patients with laboratory abnormalities were studied to
      confirm inheritance of the defects. RESULTS: Moderate hyperhomocysteinemia was
      detected in 13.1% (95% CI, 7.6% to 21.3%) and in 19.2% (CI, 9.0% to 31.9%) of
      patients with venous or arterial occlusive disease. The prevalence of
      hyperhomocysteinemia was almost twice as high when based on homocysteine
      measurements done after oral methionine load as when based on fasting levels. The
      remaining defects were detected only in patients with venous occlusive disease
      (activated protein C resistance in 11.2% of patients, protein S or C deficiency
      in 6.6%, and plasminogen deficiency in 0.9%), with an overall prevalence of 18.7%
      (CI, 12.1% to 27.6%). Inheritance of hyperhomocysteinemia and of the other
      defects was confirmed in 26 of the 30 families studied. Event-free survival
      analysis showed that the relative risk for occlusive disease in patients with
      moderate hyperhomocysteinemia and other defects was 1.70 times (CI, 1.19 to 2.42;
      P < 0.01) greater than in patients without defects. After adjustment for the
      presence of predisposing factors (for example, use of contraceptive drugs,
      pregnancy, surgery, prolonged bedrest, smoking, mild hypertension or
      dyslipidemia) and a family history of thrombosis, the age at first event of
      patients with moderate hyperhomocysteinemia was similar to that of patients with
      the other defects (26.4 +/- 11.2 years compared with 25.2 +/- 10.6 years), and
      the 43 patients with defects were significantly younger at first event than the
      114 patients without defects (25.5 +/- 11.1 years compared with 31.0 +/- 12.3; P
      < 0.005). Patients with mild hyperhomocysteinemia had a higher rate of recurrence
      than those without defects (52% compared with 25%; P = 0.01); among the 56
      patients who had their first event more than 1 year before observation, the
      recurrence rate was higher (80% [CI, 51% to 95%]) in patients with defects than
      in patients without defects (41% [CI, 26% to 57%] P = 0.01). CONCLUSIONS:
      Moderate hyperhomocysteinemia may have pathogenic significance in premature
      venous and arterial occlusive disease and should be included among the
      (inherited) disorders of venous and arterial thrombophilia.

PMID- 7574193
TI  - Blood pressure control, proteinuria, and the progression of renal disease. The
      Modification of Diet in Renal Disease Study.
AB  - OBJECTIVE: To examine the relations among proteinuria, prescribed and achieved
      blood pressure, and decline in glomerular filtration rate in the Modification of
      Diet in Renal Disease Study. DESIGN: 2 randomized trials in patients with chronic
      renal diseases of diverse cause. SETTING: 15 outpatient nephrology practices at
      university hospitals. PATIENTS: 840 patients, of whom 585 were in study A
      (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study
      B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients
      who required insulin were excluded. INTERVENTIONS: Patients were randomly
      assigned to a usual blood pressure goal (target mean arterial pressure, < or =
      107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients >
      or = 61 years of age) or a low blood pressure goal (target mean arterial
      pressure, < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg
      for patients > or = 61 years of age). MAIN OUTCOME MEASURES: Rate of decline in
      glomerular filtration rate and change in proteinuria during follow-up. RESULTS:
      The low blood pressure goal had a greater beneficial effect in persons with
      higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01).
      Glomerular filtration rate declined faster in patients with higher achieved blood
      pressure during follow-up in both study A (r = -0.20; P < 0.001) and study B (r =
      -0.34; P < 0.001), and these correlations were stronger in persons with higher
      baseline proteinuria (P < 0.001 in study A; P < 0.01 in study B). In study A, the
      association between decline in glomerular filtration rate and achieved follow-up
      blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial
      pressure. In both studies, the low blood pressure goal significantly reduced
      proteinuria during the first 4 months after randomization. This, in turn,
      correlated with a slower subsequent decline in glomerular filtration rate.
      CONCLUSIONS: Our study supports the concept that proteinuria is an independent
      risk factor for the progression of renal disease. For patients with proteinuria
      of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg
      (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean
      arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable.
      The extent to which lowering blood pressure reduces proteinuria may be a measure
      of the effectiveness of this therapy in slowing the progression of renal disease.

PMID- 7574194
TI  - Predicting who dies depends on how severity is measured: implications for
      evaluating patient outcomes.
AB  - OBJECTIVE: To determine whether assessments of illness severity, defined as risk
      for in-hospital death, varied across four severity measures. DESIGN:
      Retrospective cohort study. SETTING: 100 hospitals using the MedisGroups severity
      measure. PATIENTS: 11 880 adults managed medically for acute myocardial
      infarction; 1574 in-hospital deaths (13.2%). MEASUREMENTS: For each patient,
      probability of death was predicted four times, each time by using patient age and
      sex and one of four common severity measures: 1) admission MedisGroups scores for
      probability of death scores; 2) scores based on values for 17 physiologic
      variables at time of admission; 3) Disease Staging's probability-of-mortality
      model; and 4) All Patient Refined Diagnosis Related Groups (APR-DRGs). Patients
      were ranked according to probability of death as predicted by each severity
      measure, and rankings were compared across measures. The presence or absence of
      each of six clinical findings considered to indicate poor prognosis in patients
      with myocardial infarction (congestive heart failure, pulmonary edema, coma, low
      systolic blood pressure, low left ventricular ejection fraction, and high blood
      urea nitrogen level) was determined for patients ranked differently by different
      severity measures. RESULTS: MedisGroups and the physiology score gave 94.7% of
      patients similar rankings. Disease Staging, MedisGroups, and the physiology score
      gave only 78% of patients similar rankings. MedisGroups and APR-DRGs gave 80% of
      patients similar rankings. Patients whose illnesses were more severe according to
      MedisGroups and the physiology score were more likely to have the six clinical
      findings than were patients whose illnesses were more severe according to Disease
      Staging and APR-DRGs. CONCLUSIONS: Some pairs of severity measures assigned very
      different severity levels to more than 20% of patients. Evaluations of patient
      outcomes need to be sensitive to the severity measures used for risk adjustment.

PMID- 7574195
TI  - Prophylaxis of Plasmodium falciparum malaria with azithromycin administered to
      volunteers.
AB  - OBJECTIVE: To determine whether azithromycin, 250 mg/d, is effective prophylaxis
      for liver infection or for both liver and subsequent blood infection with
      Plasmodium falciparum. DESIGN: Controlled phase II trial with two cohorts entered
      sequentially. SETTING: Clinical trials center of Walter Reed Army Institute of
      Research, Washington, D.C. PATIENTS: Each of the two cohorts consisted of 12
      normal adult volunteers who had not had malaria during the previous 2 years: 10
      who received azithromycin prophylaxis and 2 controls who did not received
      treatment. INTERVENTION: For cohort 1, prophylactic efficacy against liver
      infection alone during the initial 7 days of the infection was determined by
      loading participants with azithromycin before challenge with P. falciparum
      infected mosquitoes on day 0 and by then giving the drug for 7 days after the
      challenge. The regimen was 500 mg on day 14 before the challenge, followed by 250
      mg/d from day 13 before the challenge through day 7 after the challenge. For
      cohort 2, prophylactic efficacy against both the liver infection and the
      subsequent blood infection was determined by continuing drug administration for
      28 days after the challenge. MEASUREMENTS: Plasmodium falciparum infection was
      diagnosed through peripheral blood smears obtained up to 70 days after challenge.
      Malarial symptoms and adverse drug reactions were also monitored. RESULTS: In
      cohort 1, 4 of 10 volunteers who received azithromycin prophylaxis (40%) did not
      develop parasitemia. In cohort 2, none of the 10 volunteers receiving
      azithromycin prophylaxis (100%) developed parasitemia. For each cohort, both
      control volunteers became parasitemic on days 9 through 13 after the challenge.
      Adverse drug reactions were few and mild. CONCLUSIONS: In this model, prophylaxis
      with azithromycin (250 mg/d) was partially effective against liver parasites and
      completely successful against the combination of liver and blood parasites. These
      data suggest that azithromycin has the potential to be an effective, well
      tolerated clinical prophylactic agent for P. falciparum malaria.

PMID- 7574196
TI  - Violence in intimate relationships and the practicing internist: new "disease" or
      new agenda?
AB  - Domestic violence is endemic in U.S. society and is seen in nearly every venue of
      medical care. A history of abuse should be considered and routinely queried in
      all women who present for emergency care, should be suspected in any woman who
      presents with an injury, and should be routinely screened for in primary care
      settings. Clinical manifestations, suggested diagnostic strategies, obstacles to
      leaving the abusive relationship, and the barriers that patients face in
      obtaining and that physicians face in providing optimal care in situations of
      domestic violence are discussed. Physicians can play a pivotal role in primary
      prevention, early intervention, and follow-up care during and after an episode of
      intimate partner violence. Clinical competence in the treatment and prevention of
      family violence is an important component of the new agenda for health care,
      particularly in generalist fields such as general internal medicine.

PMID- 7574197
TI  - Sexual and physical abuse and gastrointestinal illness. Review and
      recommendations.
AB  - OBJECTIVES: To summarize the existing data on abuse history and gastrointestinal
      illness, suggest a conceptual scheme to explain these associations, suggest ways
      to identify patients at risk, and provide information about mental health
      referral. DATA SOURCES: Review of the pertinent literature by clinicians and
      investigators at referral centers who are involved in the care of patients with
      complex gastrointestinal illness and who have experience in the diagnosis and
      care of patients with abuse history in these settings. STUDY SELECTION: All
      research articles and observational data that addressed abuse history in
      gastroenterologic settings. Articles were identified through a MEDLINE search.
      DATA EXTRACTION: Independent extraction by multiple observers. DATA SYNTHESIS: On
      the basis of literature review and consensus, it was determined that abuse
      history is associated with gastrointestinal illness and psychological
      disturbance; appears more often among women, patients with functional
      gastrointestinal disorders, and patients seen in referral settings; is not
      usually known by the physician; and is associated with poorer adjustment to
      illness and adverse health outcome. Although the mechanisms for this association
      are unknown, psychological factors (somatization, response bias, reinforcement of
      abnormal illness behavior) and physiologic factors (psychophysiologic response,
      enhanced visceral sensitivity) probably contribute. On the basis of these data,
      recommendations are made on how to identify patients at risk, how to obtain this
      information, and, if needed, how to make appropriate referrals. CONCLUSIONS: The
      authors agree with existing data on the association between abuse history and
      gastrointestinal illness. Physicians should ask patients with severe or
      refractory illness about abuse history. Appropriate referral to a mental health
      professional may improve the clinical outcome.

PMID- 7574198
TI  - The mini-CEX (clinical evaluation exercise): a preliminary investigation.
AB  - OBJECTIVE: To gather preliminary data on the mini-CEX (clinical evaluation
      exercise), a device for assessing the clinical skills of residents. DESIGN:
      Evaluation of residents by faculty members using the mini-CEX. SETTING: 5
      internal medicine training programs in Pennsylvania. PARTICIPANTS: 388 mini-CEX
      encounters involving 88 residents and 97 evaluators. MEASUREMENTS: A mini-CEX
      encounter consists of a single faculty member observing a resident while that
      resident conducts a focused history and physical examination in any of several
      settings. After asking the resident for a diagnosis and treatment plan, the
      faculty member rates the resident and provides educational feedback. The
      encounters are intended to be short (about 20 minutes) and to occur as a routine
      part of training so that each resident can be evaluated on several occasions by
      different faculty members. RESULTS: The encounters occurred in both inpatient and
      ambulatory settings and were longer than anticipated (median duration, 25
      minutes). Residents saw either new or follow-up patients who collectively
      presented with a broad range of clinical problems. The median evaluator assessed
      two residents and was generally satisfied with the mini-CEX format; residents
      were even more satisfied with the format. The reproducibility of the mini-CEX is
      higher than that of the traditional CEX, and its measurement characteristics are
      similar to those of other test formats, such as standardized patients and
      standardized oral examinations. CONCLUSIONS: The mini-CEX assesses residents in a
      much broader range of clinical situations than the traditional CEX, has better
      reproducibility, and offers residents greater opportunity for observation and
      feedback by more than one faculty member and with more than one patient. On the
      other hand, the mini-CEX may be more difficult to administer because multiple
      encounters must be scheduled for each resident. Exclusive use of the mini-CEX
      also prevents residents from being observed while doing a complete history and
      physical examination. Given the promising results and measurement characteristics
      of the mini-CEX, however, the American Board of Internal Medicine encourages the
      use of this method in conjunction with or as an alternative to the traditional
      CEX.

PMID- 7574199
TI  - From public health to personal health: violence against women across the life
      span.

PMID- 7574200
TI  - A report card for report cards.

PMID- 7574201
TI  - Communion.

PMID- 7574202
TI  - A new range for the anion gap.

PMID- 7574203
TI  - External influences on left ventricular diastolic pressure.

PMID- 7574204
TI  - Reducing suppressive therapy in patients with a history of thyroid cancer.

PMID- 7574205
TI  - Reevaluation of amiodarone.

PMID- 7574206
TI  - Reevaluation of amiodarone.

PMID- 7574207
TI  - Renal aneurysms and IgA nephropathy.

PMID- 7574208
TI  - Trimethoprim--sulfamethoxazole prophylaxis of spontaneous bacterial peritonitis.

PMID- 7574209
TI  - Percutaneous transcatheter arterial embolization for hypersplenism.

PMID- 7574210
TI  - Not for money, but for life.

PMID- 7574211
TI  - SIADH in a patient receiving sertraline.

PMID- 7574212
TI  - Prioritizing or rationing health care.

PMID- 7574213
TI  - Screening surgeons for HIV infection.

PMID- 7574214
TI  - Preventing firearm violence.

PMID- 7574215
TI  - Preventing firearm violence.

PMID- 7574216
TI  - Preventing firearm violence.

PMID- 7574217
TI  - Preventing firearm violence.

PMID- 7574218
TI  - HIV-1 messenger RNA in peripheral blood mononuclear cells as an early marker of
      risk for progression to AIDS.
AB  - OBJECTIVE: To establish human immunodeficiency virus type 1 (HIV-1) messenger RNA
      (mRNA) expression in peripheral blood mononuclear cells as a marker of risk for
      progression to the acquired immunodeficiency syndrome (AIDS) in a large cohort of
      HIV-infected persons followed for a prolonged period. DESIGN: Retrospective
      testing of cryopreserved, coded specimens. SETTING: Research laboratories at the
      New York Blood Center and the Rockefeller University. PATIENTS: 150 homosexual
      men infected with HIV-1 who did not have an AIDS diagnosis at the time of
      testing. MEASUREMENTS: Multiply spliced and unspliced HIV-1 mRNAs in total
      peripheral blood mononuclear cell RNA were quantitated using reverse
      transcriptase-initiated polymerase chain reaction (PCR) and compared with other
      laboratory data and clinical outcome during the subsequent 8 years. RESULTS:
      Although HIV-1 mRNA expression generally correlated with immunologic status, it
      was associated with future disease progression independently of CD4+ cell counts
      or their rate of decrease at the time of sampling. The association of HIV-1 mRNA
      with disease progression in persons with CD4+ cell counts higher than the median
      (> 624 cells/mm3) was particularly noteworthy; further variation in the CD4+ cell
      counts within this group was not prognostically significant. CONCLUSIONS: The
      expression of HIV-1 mRNA in peripheral blood mononuclear cells is a strong
      independent marker for future HIV disease progression, even in persons with
      normal T-cell subsets.

PMID- 7574219
TI  - Lack of effect of aspirin in asymptomatic patients with carotid bruits and
      substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group.
AB  - OBJECTIVE: To determine the effectiveness of aspirin in preventing ischemic
      events in patients with asymptomatic carotid stenosis. DESIGN: Double-blind,
      placebo-controlled trial. SETTING: University-affiliated hospitals. PATIENTS: 372
      neurologically asymptomatic patients with carotid stenosis of 50% or more in at
      least one artery as determined by luminal diameter reduction on duplex
      ultrasonography. INTERVENTION: Patients were randomly assigned to receive either
      enteric coated aspirin, 325 mg/d, or identically appearing placebo. Duration of
      therapy was 2.0 years for the aspirin recipients and 1.9 years for the placebo
      recipients. OUTCOME MEASURES: Patients were scheduled for a clinical examination
      every 6 months for assessment of the occurrence of any clinical event in the
      composite end point, which consisted of transient ischemic attack, stroke,
      myocardial infarction, unstable angina, or death. RESULTS: At baseline, the 188
      patients receiving aspirin and the 184 patients receiving placebo had similar
      demographic, ultrasonographic, and laboratory characteristics. The median
      duration of follow-up was 2.3 years. The annual rate of all ischemic events and
      death from any cause was 12.3% for the placebo group and 11.0% for the aspirin
      group (P = 0.61). The Cox proportional hazards analysis yielded an adjusted
      hazard ratio (aspirin-placebo) of 0.99 (95% CI, 0.67 to 1.46; P = 0.95). The
      annual rates for vascular events only were 11% for the placebo group and 10.7%
      for the aspirin group (P = 0.99). The multivariate analysis yielded a hazard
      ratio of 1.08 (CI, 0.72 to 1.62; P = 0.71). CONCLUSION: Aspirin did not have a
      significant long-term protective effect in asymptomatic patients with high-grade
      (> or = 50%) carotid stenosis.

PMID- 7574220
TI  - Polycythemia vera: the natural history of 1213 patients followed for 20 years.
      Gruppo Italiano Studio Policitemia.
AB  - OBJECTIVE: To reassess the natural history of polycythemia vera and to obtain
      reliable estimates of both incidence of thrombosis and survival for use in
      defining the sample size for therapeutic clinical trials. STUDY DESIGN:
      Retrospective cohort study of patients with polycythemia who had been followed
      for 20 years. SETTING: 11 Italian hematology institutions. PATIENTS: 1213
      patients with polycythemia vera, which was diagnosed according to criteria
      established by the Polycythemia Vera Study Group and commonly used in clinical
      practice. MAIN OUTCOME MEASURES: All-cause mortality, venous and arterial
      thrombosis, and hematologic and nonhematologic neoplastic disease. Myocardial
      infarction and stroke were classified as major thrombotic events, and venous and
      peripheral arterial thrombosis were considered minor thrombotic events. The
      number of patients who died and the number of those who had major thrombotic
      events (combined end point) were used as a comprehensive measure of the benefit
      risk ratio associated with the use of myelosuppressive agents. RESULTS: 634 fatal
      and nonfatal arterial and venous thromboses were recorded in 485 patients (41%);
      36% of these episodes occurred during follow-up in 230 patients (19%), and 64%
      occurred either at presentation or before diagnosis. Thrombotic events occurred
      more frequently in the 2 years preceding diagnosis, suggesting a causal relation
      between the latent myeloproliferative disorder and the vascular event. The
      incidence of thrombosis during follow-up was 3.4%/y; older patients or those with
      a history of thrombosis had a higher risk for thrombosis. Overall mortality was
      2.9/100 patients per year; thrombotic events and hematologic or nonhematologic
      cancers had similar effects on mortality. Patients receiving chemotherapy died
      three to four times more frequently than those not receiving chemotherapy. The
      increased risk for cancer in patients receiving myelosuppressive agents was seen
      approximately 6 years after diagnosis. In addition, the combined end point,
      computed as the sum of the hardest available events (death, nonfatal myocardial
      infarction, or stroke), suggests that myelosuppressive agents have an overall
      unfavorable effect. CONCLUSIONS: Cytoreduction favorably affects the incidence of
      thrombotic events, but aggressive treatment seems to be associated with increased
      risk for neoplasm. These results provide a basis for reevaluating the therapeutic
      strategy in patients with polycythemia vera and for estimating the size of
      clinical trials aimed at testing new therapeutic approaches.

PMID- 7574221
TI  - A cost analysis of alternative treatments for duodenal ulcer.
AB  - OBJECTIVE: To compare the costs of alternative strategies for the treatment of
      duodenal ulcer. DESIGN: A cost comparison using decision analysis. METHODS: A
      decision model was used to compare the costs per cure of an endoscopically
      documented duodenal ulcer for three initial treatment strategies: 1) H2-receptor
      antagonist therapy for 8 weeks, 2) antibiotic therapy for Helicobacter pylori
      infection plus H2-receptor antagonist therapy, and 3) urease test-based
      treatment. For symptomatic recurrences, secondary treatment strategies included
      empiric retreatment with the same or other regimen, and treatment based on repeat
      endoscopy-guided urease test or biopsy, with an assumption of subsequent cure.
      The cohort modeled for this analysis consisted of patients at low risk for a
      malignant ulcer. Probability estimates were derived from published clinical
      trials, cohort studies, and expert opinion. Side effects from combination therapy
      with antibiotics and H2-receptor antagonists and resulting costs were included
      from the perspective of a group practice model health maintenance organization.
      RESULTS: For all secondary treatment strategies, initial therapy with antibiotics
      for H. pylori infection plus an H2-receptor antagonist resulted in the lowest
      average costs per symptomatic cure when the prevalence or likelihood of H. pylori
      infection exceeded 66% to 76%; the costs ranged from $284 for secondary
      (re)treatment with empiric antibiotic and H2-receptor antagonist therapy to $398
      for endoscopy-guided secondary treatment. Initial treatment with an H2-receptor
      antagonist resulted in the highest costs, ranging from $372 for secondary
      treatment with empiric antibiotic and H2-receptor antagonist therapy to $679 for
      endoscopy-guided secondary treatment. The results were not sensitive to the rates
      of duodenal ulcer recurrence after either treatment, to the cost of either
      treatment, or to prevalence of H. pylori. CONCLUSIONS: This cost analysis
      indicates that, regardless of the secondary treatment used for ulcer recurrence,
      initial therapy with antibiotics for H. pylori infection plus an H2-receptor
      antagonist provides the lowest costs per symptomatic cure. These cost savings and
      the lower recurrence rates associated with this treatment favor eradication of H.
      pylori as part of the initial treatment of duodenal ulcer.

PMID- 7574222
TI  - Changes in energy balance and body composition at menopause: a controlled
      longitudinal study.
AB  - OBJECTIVE: To describe the effects of menopause on resting metabolic rate, body
      composition, fat distribution, physical activity during leisure time, and fasting
      insulin levels. DESIGN: A longitudinal comparison of metabolic changes in women
      who experienced menopause with changes in age-matched women who did not
      experience menopause. SETTING: General clinical research center. PATIENTS: An
      initial cohort of 35 sedentary healthy premenopausal women (age range, 44 to 48
      years). After 6 years of follow-up, 18 women had spontaneously stopped
      menstruating for at least 12 months and 17 women remained premenopausal. No women
      received hormone replacement therapy. RESULTS: Women who experienced menopause
      lost more fat-free mass than women who remained premenopausal (-3.0 +/- 1.1 kg
      and -0.5 +/- 0.5 kg, respectively), had greater decreases in resting metabolic
      rate (-103 +/- 55 kcal/d and -8 +/- 17 kcal/d) and physical activity during
      leisure time (-127 +/- 79 kcal/d and 64 +/- 60 kcal/d), and had greater increases
      in fat mass (2.5 +/- 2 kg and 1.0 +/- 1.5 kg), fasting insulin levels (11 +/- 9
      pmol/L and -2 +/- 5 pmol/L), and waist-to-hip ratios (0.04 +/- 0.01 and 0.01 +/-
      0.01) (P < or = 0.01 for all comparisons). Menopause did not affect energy
      intake, fasting glucose levels, or peak oxygen consumption. CONCLUSIONS: Natural
      menopause is associated with reduced energy expenditure during rest and physical
      activity, an accelerated loss of fat-free mass, and increased central adiposity
      and fasting insulin levels. These changes may indicate a worsening cardiovascular
      and metabolic risk profile.

PMID- 7574223
TI  - Digitalis-induced visual disturbances with therapeutic serum digitalis
      concentrations.
AB  - OBJECTIVE: To assess the role of digitalis in the development of visual symptoms
      severe enough to warrant ophthalmologic consultation in patients who received
      digitalis and who had no other clinical or laboratory evidence of digitalis
      toxicity. DESIGN: Clinical case study. SETTING: Neuro-ophthalmology referral
      practice. PATIENTS: Six elderly patients (aged 66 to 85 years) who received
      digitalis were referred to ophthalmologists for evaluation of photopsia (five
      patients) or decreased visual acuity (one patient). No patient had chromatopsia
      or nonvisual clinical manifestations of digitalis intoxication at the time of
      examination. MEASUREMENTS: All patients had serum digitalis concentrations within
      or below the therapeutic range. In most patients, the electroretinographic cone b
      wave implicit time was longer than normal. RESULTS: Discontinuation of digitalis
      therapy, which was possible in five patients, was followed by resolution of
      visual symptoms and by shortening of the b-wave implicit time. Characteristic
      features of digitalis-induced photopsia were its dependence on illumination and
      its tendency to be localized in peripheral visual fields. CONCLUSIONS: In an
      elderly patient receiving digitalis, the development of photopsia characterized
      by innumerable points of light in the peripheral visual fields or a decrease in
      visual acuity raises the possibility that the patient's visual disturbance may
      have been digitalis induced. Digitalis-induced visual disturbances other than
      chromatopsia or disturbances of color vision may occur in elderly patients who
      have no other clinical manifestations of digitalis intoxication and who have a
      serum digitalis concentration within or below the therapeutic range.

PMID- 7574224
TI  - Pain evaluation and management in the nursing home.
AB  - As many as 45% to 80% of nursing home residents have pain that contributes
      materially to functional impairment and decreased quality of life. Substantial
      barriers, including a high frequency of dementia, multiple pain problems, and
      increased sensitivity to drug side effects often make pain assessment and
      management more difficult in the nursing home setting. Logistic problems in
      carrying out diagnostic procedures and management interventions are also common.
      Pain can be alleviated in nursing homes through the careful use of analgesic
      drugs combined with nonpharmacologic strategies, including exercise programs and
      other physical therapies. Elderly nursing home residents are more sensitive to
      the side effects associated with many analgesic drugs, but this does not justify
      the failure to treat pain, especially in those who are terminally ill or near the
      end of life. Structured programs for routine pain assessment and treatment are
      needed. Physician involvement in pain assessment and management is necessary if
      pain control is to be improved for nursing home patients.

PMID- 7574225
TI  - Diagnosing and treating patients with refractory functional gastrointestinal
      disorders.
AB  - One of the clinician's most difficult tasks is to successfully care for patients
      with painful and refractory functional gastrointestinal disorders. Because the
      diagnosis of these disorders is never assured and symptomatic treatments are not
      always successful, these patients are susceptible to receiving unnecessary,
      costly, and sometimes risky studies and treatments. This article offers an
      approach to the diagnosis and care of these patients that emphasizes 1) using a
      diagnostic strategy that incorporates symptom-based criteria, a screening
      evaluation, early symptomatic treatment, symptom monitoring, and reassessment; 2)
      asking several questions during the first visit to assess the psychosocial
      contributions to the illness; 3) developing an effective patient-physician
      relationship through empathy, reassurance, education, and a negotiated and
      realistic treatment plan; and 4) providing the option for psychological
      consultation and treatment as a way to help the patient better control symptoms.
      This approach is likely to improve patient and physician satisfaction, adherence
      to treatment, and clinical outcome.

PMID- 7574226
TI  - Escherichia coli O157:H7 infection in humans.
AB  - OBJECTIVE: To review the clinical relevance of Escherichia coli O157:H7
      infection, including the epidemiology of the infection and its clinical
      presentations, pathogenesis, microbiology, diagnosis, treatment, and prevention.
      DATA SOURCES: Articles on E. coli O157:H7 were identified through MEDLINE and the
      bibliographies of relevant articles. STUDY SELECTION: All articles and case
      reports describing E. coli O157:H7 and its infection were selected. DATA
      EXTRACTION: The data were abstracted without judgments about study design. Data
      quality and validity were assessed by independent author reviews. DATA SYNTHESIS:
      Infection with E. coli O157:H7 presents with a wide spectrum of clinical
      manifestations, including asymptomatic carriage, nonbloody diarrhea, hemorrhagic
      colitis, the hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura.
      Not only is E. coli O157:H7 an important agent for hemorrhagic colitis, it is
      also one of the leading causes of bacterial diarrhea. Patients at extremes of age
      have an increased risk for infection and associated complications. Transmission
      of E. coli O157:H7 is primarily food-borne. Undercooked meat is the most common
      culprit, and secondary person-to-person spread is also important. The organism
      produces at least two Shiga-like toxins that differ antigenically,
      physicochemically, immunologically, and in their biological effects. These toxins
      are thought to have direct pathogenic significance in E. coli O157:H7 infection.
      This infection is usually diagnosed from a positive stool culture, from the
      presence of Shiga-like toxins, or both. Timely collection (within 7 days of
      illness onset) of a stool sample for culture is imperative for a high recovery
      rate. Treatment is primarily supportive and includes the management of
      complications as necessary. Antibiotic therapy has not been proved beneficial.
      Important public health measures include educating the public on the danger of
      eating undercooked meat, increasing physician awareness of E. coli O157:H7
      infection, and mandating case reporting. CONCLUSIONS: Infection with E. coli
      O157:H7 presents with many clinical manifestations and should be included in the
      differential diagnosis for any patient with new-onset bloody diarrhea.
      Development of the hemolytic-uremic syndrome or thrombotic thrombocytopenic
      purpura should raise strong suspicion of E. coli O157:H7 infection and should
      lead to prompt evaluation. If infection is confirmed, it should be reported to
      public health officials.

PMID- 7574227
TI  - Prevention of HIV infection in primary care: current practices, future
      possibilities.
AB  - More than a decade has passed since the human immunodeficiency virus (HIV) and
      the acquired immunodeficiency syndrome (AIDS) epidemic began; our failure to
      develop an effective vaccine and adequate medical treatments indicates that
      future research and practice must work to prevent the spread of HIV. We review
      the literature on the current HIV-prevention practices of primary care physicians
      and highlight opportunities for clinical prevention. Prevention is hindered in
      four ways: 1) by narrow conceptions of medical care and of the role of the
      physician; 2) by physicians' discomfort with discussing human sexuality and
      illicit drug use and their attitudes toward persons with HIV or AIDS; 3) by
      constraints on time and resources; and 4) by the ambiguity of HIV prevention
      messages. We suggest strategies to overcome these barriers, including
      modifications in public policy, health care delivery systems, and medical
      education. These strategies support a nonhierarchical physician-patient
      relationship, with attention to culture and values, that will help physicians to
      identify and work with persons at increased risk for HIV infection.

PMID- 7574228
TI  - Medical compared with surgical treatment of asymptomatic carotid artery stenosis.
AB  - The Asymptomatic Carotid Atherosclerosis Study (ACAS) results suggest that
      carotid endarterectomy combined with aspirin and risk factor reduction is
      superior to aspirin and risk factor reduction is superior to aspirin and risk
      factor reduction alone in preventing ipsilateral stroke in asymptomatic patients
      with diameter stenosis of the carotid artery of 60% or more. The absolute risk
      reduction over 5 years conferred by surgical therapy is modest (5.9%) compared
      with the risk reduction conferred by surgical therapy for symptomatic carotid
      disease but compares favorably with the degree of stroke prevention shown for
      antihypertensive therapy in the elderly. For prevention of stroke in women and
      for prevention of major stroke, the ACAS results favoring surgery did not reach
      statistical significance. The combined arteriographic and perioperative surgery
      related mortality and stroke rates achieved by the carefully selected surgical
      teams was low (2.3%). Accordingly, carotid endarterectomy can be recommended for
      preventing stroke in the setting of hemodynamically significant stenosis when the
      arteriographic and surgical complication rates can be kept low.

PMID- 7574229
TI  - The dilemma of surgical treatment for patients with asymptomatic carotid disease.
AB  - Several case series have suggested that endarterectomy is beneficial in
      asymptomatic carotid artery disease. Four randomized trials have been done in
      this area, the most recent of which is the Asymptomatic Carotid Atherosclerosis
      Study (ACAS). Results of the first three trials were negative, and ACAS produced
      a tantalizing, statistically significant finding that does not translate into
      clinical importance. Disabling strokes have not been reduced by surgical therapy,
      and the benefit for women has not been shown. It is unclear from this study
      whether persons with the greatest stenosis and the highest vascular risk profiles
      are appropriate candidates for endarterectomy. In patients in whom carotid artery
      disease is incidentally discovered, the benefits of the prophylactic addition of
      carotid endarterectomy to coronary bypass grafting or other major surgical
      procedure in patients are still unknown. Excellent surgical skill is of paramount
      importance for the future use of this procedure. Mass population screening to
      detect asymptomatic carotid disease will only be justified when and if future
      studies identify patients in whom the risk for disabling stroke after the
      procedure is clearly reduced.

PMID- 7574230
TI  - Predicting progression to AIDS.

PMID- 7574231
TI  - Stalking sarcopenia.

PMID- 7574232
TI  - Asymptomatic carotid stenosis: the glass is half occupied.

PMID- 7574233
TI  - On being a doctor. Umana.

PMID- 7574234
TI  - Bone mineral density in non-insulin-dependent diabetes mellitus.

PMID- 7574235
TI  - Transient ischemic attack after air-contrast echocardiography.

PMID- 7574236
TI  - Body weight and bone mineral density in hyperparathyroidism.

PMID- 7574237
TI  - Renal cell carcinoma and erythropoietin.

PMID- 7574238
TI  - Methotrexate in idiopathic granulomatous hepatitis.

PMID- 7574239
TI  - Epidemic neuropathy in Cuba.

PMID- 7574240
TI  - Epidemic neuropathy in Cuba.

PMID- 7574241
TI  - [Ear prosthesis anchored on osseointegrated implants. Experience with 9 cases].
AB  - The use of osseointegrated titanium implants has improved the quality of auricle
      prosthesis fixation. Between december 1993 and july 1994, twenty two titanium
      fixtures have been surgically implanted in nine patients in the Ear Nose Throat
      department of the university hospital of Strasbourg. This method of auricle
      amputation repair achieves a good esthetic result with a low rate of
      postoperative complications.

PMID- 7574242
TI  - [Phantom responses and early auditory evoked potentials. Comparison of the TDH39
      hearing aid and an intra-canal hearing device].
AB  - Using conventional tonal audiometry, Joseph Zwislocki demonstrated in 1953 that
      the intensity of sound transfer to the opposite ear depends on the transductor
      (earphone). Interauricular attenuation is inversely proportional to the bone
      surface facing the earphone when all air transmission has been eliminated. In
      earlier work in 1982, we first concluded that this rule is applicable to auditory
      evoked potentials such as those used for conventional audiometry for unilateral
      cophosis. A TDH39 device transfers the sound to the contralateral ear with an
      attenuation of approximately 60 decibels, using the V wave latency as reference
      for calculating intensity. We verified the reality of Joseph Zwislocki's rule
      with newly available insert earphones. Surface contact with bone being smaller
      than with the TDH39, sound transfer to the opposite ear would logically be much
      more attenuated when air transmission is eliminated. The aim of this work was to
      determine sound transfer in 27 patients with unilateral cophosis undergoing
      conventional audiometry and to draw practical conclusions.

PMID- 7574243
TI  - [Inoperable tracheal and cricoid-tracheal stenoses. Results of laser therapy and
      prolonged calibration].
AB  - Palliative desobstruction was performed with laser and a Montgomery T tube in 11
      patients with tracheal or cricotracheal stenosis. Surgery was theoretically
      indicated for these long thick stenotic areas with underlying diseased cartilage
      but could not be performed due to the poor clinical status of the patients or
      recurrence after anastomosis. Calibration with the Montgomery T tube was
      maintained for a mean of 5 years. The T tube was removed in 3 patients and was
      well tolerated in 4. Two patients died during the course of the study and two
      others required a definitive tracheotomy. Palliative treatment with Laser
      desobstruction and long-term calibration can be a useful alternative to
      conventional surgery.

PMID- 7574244
TI  - [A new technique of gene transposition in the surgical treatment of sleep apnea
      syndrome].
AB  - Pharyngotomy appears to be insufficient for the treatment of severe sleep apnea.
      For patients who refuse or abandon mechanical ventilatory assistance, surgery can
      be used to widen the retrobasilingual space adapting it to the cephalometric
      profile defined by cineradiography and MRI in combination with velopharyngeal
      plasty. For patients with no maxillomandibular or lingual malformation, the
      pharyngotomy can be combined with an anterior transposition of the genial
      insertions of the tongue without rotation. A method different from that described
      by Riley and Powel is proposed. The details of the surgical procedure are
      exposed. The operation is indicated in snorers with sleep apnoea with an Apnea
      Index Superior to 30 who refuse nocturnal ventilatory assistance and who do not
      have a hypertrophied tongue (Surface less than 30 cm2) or maxillomandibular
      retroposition.

PMID- 7574245
TI  - [Acoustic parameters of voice and speech in a case of bulbar amyotrophic lateral
      sclerosis].
AB  - Pharyngolaryngeal fasciculations in a patient with bulbar amyotrophic lateral
      sclerosis are documented. The acoustical and spectrographic parameters are
      presented. A review of the symptomatic mechanisms resulting in speech and voice
      alterations of amyotrophic lateral sclerosis is performed.

PMID- 7574246
TI  - [Tonsillectomy in a day care hospital. A socioeconomic study at the Robert Debre
      Hospital in Paris].
AB  - Tonsillectomy as an outpatient procedure in children is a common practice in the
      United States and many other countries. In French public hospitals, it remains
      quite rare. A 6-month prospective study was conducted in order to check the
      procedure's feasibility in a large Paris university children's hospital, to
      describe the involved population and to search for the possible benefits which
      could be made by a public hospital from an increase in day surgery practice for
      tonsillectomy. In terms of quality of postoperative outcome, this study confirms
      the absence of major complications related to this procedure if the proper
      criteria are met for day surgery. In fact, medical and social findings from the
      involved patients tend to limit here a large extension of this procedure. For
      example, in the inpatients group, more than 43% of children had a tonsillar
      hypertrophy with significant airway obstruction and 47% did not have lodging
      conditions which would allow day surgery with the required safety. Only 20% of
      patients could be transferred to ambulatory surgery which leads to 2-3 additional
      cases each week here. Finally, the cost analysis shows no benefit in human
      resources at this hospital because the requested differential activity threshold
      would not be reached.

PMID- 7574247
TI  - [Contribution of cartilage grafts to lateral reinforcement of the nose].
AB  - Cartilage grafts were used for lateral reinforcement of the nasal pyramid in a
      series of 67 patients undergoing surgery for nasal deviation. Septal cartilage,
      used for all grafts, is a well vitalized, highly flexible tissue allowing
      remodelling to the desired form. Lateral wall reinforcement with cartilage grafts
      plays an important role in surgical cure of deviated noses. In our series of 67
      patients, this procedure was used in 61. Results were good in 83%.

PMID- 7574248
TI  - [Parathyroid adenoma as an ectopic carotid mass. Apropos of a case].
AB  - Authors report a case of parathyroid adenoma as lateral palpable cervical mass,
      with serious hypercalcemia. MRI and ultrasound investigations were performed
      preoperatively. No other pathological parathyroid gland was found. Surgical
      treatment did not include the exploration of the four parathyroid glands. Long
      term follow-up is necessary.

PMID- 7574249
TI  - [How to perform an endoscopic evaluation of the nasal cavity].

PMID- 7574250
TI  - Endoscopic surgery of Zenker's diverticula. Experience with the Dohlman
      technique. 1961.

PMID- 7574251
TI  - Adult respiratory papillomatosis: human papillomavirus type and viral
      coinfections as predictors of prognosis.
AB  - Pathologic material and the records of 29 patients with laryngeal papillomatosis
      were reviewed. The relationship between the type of human papillomavirus (HPV)
      and the presence of viral coinfections was correlated with clinical outcome.
      Using polymerase chain reaction, paraffin-embedded specimens were analyzed for
      the presence of HPV, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes
      simplex virus (HSV). The HPV type could be identified in 24 patients' specimens.
      Twenty-one patients were infected with HPV type 6. The other 3 were infected with
      HPV type 11 or 16. Three patients developed squamous cell carcinoma, of whom 2
      had HPV type 11 or 16. We found HSV, EBV, and CMV in 50%, 12.5%, and 0% of
      specimens, respectively. An aggressive clinical course was observed in 17
      patients. Evidence of coinfection with other viruses was identified in 11 (65%)
      of these patients. In contrast, a benign clinical course was observed in 7
      patients, of whom 2 (29%) had viral coinfections. We conclude that the HPV type
      and the presence of viral coinfections may be predictive of an aggressive
      clinical course.

PMID- 7574252
TI  - Quality of life after surgical treatment of cancer of the larynx.
AB  - The purpose of the study was to assess the quality of life of patients after
      surgical treatment for cancer of the larynx. Three groups of patients were
      identified according to surgical treatment: total laryngectomy, 111 patients;
      near-total laryngectomy, 38 patients; and partial laryngectomy, 23 patients. The
      impact of successful surgical treatment on their life roles was analyzed in terms
      of work, activities, familial and spousal relationships, sexuality, and
      psychologic features such as stress and anxiety. Two questionnaires were used;
      the Psychosocial Adjustment to Illness Scale (PAIS) and the Mayo Clinic
      Postlaryngectomy Questionnaire. With the PAIS questionnaire, no difference was
      found in role adjustment between the total laryngectomy and near-total
      laryngectomy groups, with one exception. In the work domain, the total
      laryngectomy patients who were working had better adjustment than the near-total
      laryngectomy patients. The overall adjustment of both groups was less favorable
      than that of a comparison group of patients with nonlaryngeal cancer. The
      patients who had the classic conservation operations adjusted in all domains more
      favorably than the patients with permanent tracheostomas. The partial operation
      patients adjusted better than the nonlaryngeal cancer patients. We conclude that
      the stoma has a negative impact on adjustment postoperatively and that it may
      have a more serious impact on life adjustment than voice alteration. Further
      investigation and standardization of measurement tools are needed.

PMID- 7574253
TI  - Hyoepiglottic ligament in supraglottic cancer.
AB  - The hyoepiglottic ligament (HL) is a connective tissue structure that serves as
      the roof of both the paraglottic and the preepiglottic spaces and thereby
      anatomically separates the supraglottic larynx from the tongue base. Whole mount
      serially sectioned larynges with supraglottic cancer were reviewed to help
      clarify cephalad spread of cancer in this region. The whole mount slides were
      analyzed from 70 laryngectomy specimens that were resected for supraglottic
      cancer. The HL was breached by cancer in 13 specimens, and all of these displayed
      clinical and histopathologic invasion of the preepiglottic and paraglottic
      spaces. Invasion of the suprahyoid epiglottis was noted in 9 specimens, and
      invasion of the aryepiglottic fold in 4. There were no instances in which cancer
      escaped from the deep compartments of the supraglottic larynx to the tongue base
      without synchronous erosion of the suprahyoid epiglottis (insertion of the medial
      HL) or the pharyngoepiglottic fold (lateral HL). The HL is a resilient connective
      tissue barrier to the spread of cancer from the supraglottis to the tongue base.
      This investigation reinforced the concept that, typically, the HL acts as a deep
      cephalad surgical boundary in resecting supraglottic cancer that 1) is confined
      to the laryngeal membranes and 2) does not clinically invade the suprahyoid
      epiglottis.

PMID- 7574254
TI  - Surface-coil magnetic resonance imaging of the internal auditory canal and the
      inner ear. Preliminary report.
AB  - Parasagittal surface-coil magnetic resonance imaging of the internal auditory
      canal and the inner ear was performed. We used T2-weighted fast spin-echo
      sequences to visualize the inner ear and the individual nerves in the internal
      auditory canal with high contrast in a short acquisition time. Computer-assisted
      quantitative measurement of the nerves was performed to estimate the cross
      sectional areas and the diameters of the nerves. The average diameters of the
      facial nerve, the cochlear nerve, and the vestibular nerve of normal-hearing
      individuals were, respectively, 1.1 +/- 0.2 mm (mean +/- SD), 1.2 +/- 0.2 mm, and
      1.5 +/- 0.2 mm. In the cerebellopontine angle, the average diameter of the eighth
      nerve was 1.8 +/- 0.2 mm. Two patients with unilateral and bilateral hearing loss
      were also presented. In the patient with unilateral deafness, the cochlear nerve
      of the diseased side was not identified and the eighth cranial nerve diameter was
      smaller than that of the normal side. In the patient with bilateral deafness,
      fibrosis of the inner ear and atrophy of the eight nerve were demonstrated in the
      ear with posttraumatic deafness. The present method may represent a new approach
      to the assessment of pathologic processes involving the inner ear and the nerves
      in the internal auditory canal.

PMID- 7574255
TI  - Method for embedding temporal bones of rats in methyl-methacrylate.
AB  - The commonly used method of preparing the temporal bone for light microscopy is a
      refinement of a basic formula that has been employed for a century. This process
      includes fixation, decalcification, neutralization, dehydration, embedding in
      celloidin, and hardening. The main disadvantage of this process is that
      decalcification is performed. This article describes a new method for preparing
      the temporal bone of rats for light microscopy. The main advantage of this new
      method is that no decalcification is involved, so that all bony elements are
      retained in their normal shape and location, and even retain some enzymatic
      activity. Other advantages are that the fixation is reversible and the process is
      short (approximately 2 weeks) and therefore relatively inexpensive. Our vast and
      positive experience with this technique has led us to report this method not in a
      specific experiment, but rather as a specific laboratory technique.

PMID- 7574256
TI  - Mitochondrial encephalomyopathy: a rare genetic cause of sensorineural hearing
      loss.
AB  - A 44-year-old man with a documented 12-year history of progressive sensorineural
      hearing loss developed a generalized tonic-clonic seizure followed by a visual
      field deficit and apraxia. Six months later he developed a peripheral neuropathy
      and muscle fatigue followed by a slowly progressive aphasia and cortical
      blindness as well as increased seizure activity. A computed tomography scan
      showed bilateral basal ganglion calcification. The serum lactate level was
      elevated at 3.4 mEq/dL. A muscle biopsy enabled the diagnosis of mitochondrial
      myopathy. This disorder is presented as an unusual cause of progressive
      sensorineural hearing loss in adults.

PMID- 7574257
TI  - Immunohistochemical study of transforming growth factor-alpha expression in
      normal and perforated tympanic membrane.
AB  - An immunohistochemical study of transforming growth factor-alpha (TGF-alpha)
      distribution was carried out to clarify the mechanism responsible for accelerated
      epidermal cell proliferation after perforation of the rabbit tympanic membrane.
      In the normal tympanic membrane, TGF-alpha expression was not observed, whereas
      after perforation, over the whole tympanic membrane including the margin of the
      perforation, TGF-alpha-positive cells appeared and were scattered in the
      epidermal cell layer. After healing of the perforation, a marked decrease of TGF
      alpha-positive cells in the tympanic membrane was observed. This finding suggests
      that TGF-alpha induces proliferation of epidermal cells after the perforation
      stimulus.

PMID- 7574258
TI  - Substance P and ciliary beat of human upper respiratory cilia in vitro.
AB  - On stimulation of trigeminal nerve endings, neuropeptides are released into the
      nasal mucosa. Among these neuropeptides is substance P(SP). In this study, we
      determined the effect in vitro of SP, as well as SP together with thiorphan, a
      blocker of the SP-degrading enzyme neutral endopeptidase, on the ciliary beat
      frequency (CBF) of the human upper respiratory tract. Ciliated epithelium of
      human adenoid tissue was used in the experiments. The CBF was measured by means
      of a computer-assisted photoelectric method. Substance P(10(-8) to 10(-5) mol/L,
      n = 7) showed a small but statistically significant dose-dependent decrease in
      CBF. On perfusion with SP (10(-8)) to 10(-5) mol/L, n = 8) in combination with
      thiorphan, no statistically significant effect was found. We conclude that SP
      does not have a direct effect on ciliary activity to such an extent that it will
      affect mucociliary transport in vivo.

PMID- 7574259
TI  - Dendritic cells in the normal human tympanic membrane.
AB  - Dendritic cells (DCs) are antigen-presenting cells that possess an outstanding
      capacity to initiate primary immune responses. They reside in the tissues in an
      immunologically immature state. Upon antigenic challenge in vivo or short-term
      culture in vitro, they undergo a maturation process and turn into mature
      "lymphoid DCs." Langerhans cells (LCs) of the epidermis were identified as
      members of this DC system. They have been demonstrated in cholesteatoma matrix
      and in inflamed tympanic membranes, but the normal tympanic membrane was hitherto
      thought to be devoid of them. To clarify this question, we removed 12 normal
      tympanic membranes postmortem and processed them for a sheet preparation. The
      epidermal layers were peeled off and immunostained with the following monoclonal
      antibodies: HLA-DR, OKT6/CD1a, and LAG (specific for the Birbeck granules of
      LCs). Two tympanic membranes were also processed for routine electron microscopy.
      In all epidermal sheets a dense network of DCs could be demonstrated. They showed
      a positive immunostaining reaction with HLA-DR, but a negative one with OKT6 and
      LAG. Thus, they differ in their immunohistochemical properties from typical
      epidermal LCs. At the ultrastructural level, DCs could also be identified, but
      without the typical Birbeck granules. This explains the negative reaction with
      the LAG antibody. These findings were extended and supported by a tissue culture
      examination of three normal tympanic membranes. After 3 days, typical "veiled"
      cells (ie, mature DCs), showing positive immunostaining with HLA-DR, could be
      recovered from the culture medium. In an oxidative mitogenesis assay, these cells
      displayed strong stimulatory capacity for resting T lymphocytes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7574260
TI  - Congenital midline cervical cleft. Case report and review.
AB  - Congenital midline cervical cleft is a rare disorder with a wide range of
      presentations. To date, there have been fewer than 35 cases reported in the
      English-language literature. A rarer finding is the association of bronchogenic
      cysts or respiratory epithelium with the midline cleft. The clinical presentation
      of congenital midline cervical cleft with a cephalic skin tab, atrophic cleft,
      and caudal sinus may distinguish it from other conditions of the midline neck. We
      present an 18-month-old girl with congenital midline cervical cleft to illustrate
      its clinical presentation and the proper treatment of this condition.

PMID- 7574261
TI  - Age- and gender-related trends in the expression of glutathione S-transferases in
      human nasal mucosa.
AB  - The cellular expression of alpha, mu, and pi classes of glutathione S
      transferases (GSTs) was investigated in human nasal mucosa by means of
      immunocytochemical techniques. In the olfactory mucosa, immunoreactivity for GST
      alpha was most intense in the acinar cells of the Bowman's glands, with weak
      immunoreactivity in the supranuclear region of sustentacular cells. Whereas GST
      pi was localized only in the sustentacular cells, no GST-mu was detected. In the
      respiratory mucosa, GST-alpha and GST-pi were detected at the brush borders of
      ciliated columnar epithelial cells. There were age- and gender-related trends in
      the expression of GST-alpha, but not GST-pi, in the olfactory mucosa. The
      intensity of immunoreactivity in the olfactory mucosa was decreased in older
      subjects. The expression of GST-alpha in the olfactory mucosa of females
      consistently exhibited greater intensity than that of males at all the ages
      studied. These differences were not observed in the respiratory mucosa. These
      results indicate that acinar cells of the Bowman's glands and sustentacular cells
      are the major sites of phase II biotransformation in the human nasal mucosa.

PMID- 7574262
TI  - Vestibular nerve compression in Camurati-Engelmann disease.

PMID- 7574263
TI  - Magnetic resonance imaging of cochlear otosclerosis.

PMID- 7574264
TI  - Mycobacterial disease of the head and neck: current perspective.
AB  - The worldwide increase in mycobacterial diseases, tuberculous and nontuberculous,
      and their association with human immunodeficiency virus infection has had and
      will continue to have an impact on the practice of otolaryngologist-head and neck
      surgeons. Epidemiologic and ecologic changes in tuberculosis and nontuberculous
      mycobacterial diseases tend to blur former clinicopathologic distinctions among
      these groups, especially in immunocompromised hosts. Diagnosis depends on
      objective identification of the mycobacterium, a process facilitated by molecular
      diagnostics.

PMID- 7574265
TI  - Quantification for staging sinusitis. The Staging and Therapy Group.
AB  - A method of quantifying the symptoms, radiologic data, and endoscopic findings in
      extensive sinus disease is proposed. It is intended to enable clinicians to
      classify patients with extensive sinus disease according to severity of disease
      and prognostic category. The rubric of extensive sinus disease, for scoring and
      staging, comprises recurrent acute sinusitis and chronic sinusitis, but not an
      isolated episode of acute sinusitis. The method assigns simple numeric scores to
      specific computed tomography findings, elements of surgical history, presence of
      defining symptoms of sinusitis, and endoscopic appearance. This quantitative
      system may be rationalized into a staging system.

PMID- 7574266
TI  - Medical management of sinusitis: educational goals and management guidelines. The
      International Conference on sinus Disease.
AB  - The primary goal of sinusitis management is resolution of infection, leading to
      patency of the ostiomeatal complex. Antibiotics and decongestants are the
      cornerstones of therapy for acute sinusitis. Diagnosis of acute sinusitis is
      based on the history and physical findings. Sinusitis is considered to be acute
      or recurrent acute if infection resolves without residual mucosal damage. Choices
      for first-line antibiotic therapy include adequate dosages of trimethoprim
      sulfamethoxazole, loracarbef, and amoxicillin-clavulanate. Decongestants and
      mucoevacuants may reduce tissue edema, facilitate drainage, and maintain ostial
      patency. Topical corticosteroids are useful additional therapy in allergic
      rhinosinusitis and as an aid in the long-term management of chronic sinusitis.
      Parenteral corticosteroids have no role in first-line management of acute or
      recurrent acute sinusitis.

PMID- 7574267
TI  - Paranasal sinuses:anatomic terminology and nomenclature.
AB  - A consensus on the preferred modern usage of potentially confusing or ambiguous
      terms in sinus anatomy and nomenclature is described. These terms are intended to
      provide clear communication among otorhinolaryngologists and serve as a basis for
      discussion among anatomists. Terminology is in English and based on Latin
      nomenclature. An attempt has been made to reconcile or eliminate duplication,
      redundancy, and overlap in terminology that have arisen over the past century. A
      key concept is that the ethmoid complex is divided into anterior and posterior
      sections by the basal lamella of the middle turbinate.

PMID- 7574268
TI  - [Parkinson disease and the neuronal dopamine uptake complex].
AB  - The dopamine carrier (dopamine uptake complex) is located on the membrane of
      dopaminergic neurons in a diffuse pattern. It is involved in the uptake of the
      dopamine released into the synaptic cleft. Considered at the level of nigro
      striatal dopaminergic neurons, whose degeneration is responsible for the
      Parkinson's disease, this carrier seems to constitute a major target. It could be
      involved in the nigro-striatal neurodegeneration by concentrating neurotoxins.
      Its in vivo labelling by position emitting agents should allow evidencing of a
      partial striatal dopaminergic denervation, before the occurrence of
      extrapyramidal troubles. Its blockable by pure dopamine uptake inhibitors, by
      preventing the neuronal concentration of toxins, could stop the neurodegeneration
      process. These agents by inhibiting the dopamine reuptake, could also lessen
      extrapyramidal troubles as well as the depressive manifestations which are
      frequently associated to Parkinson's disease.

PMID- 7574269
TI  - [PCR: principles and prospects in clinical biology].
AB  - In the short time it has been available, the Polymerase Chain Reaction (PCR) has
      been rapidly established as a powerful tool for the analysis of genes leading to
      a wide spread of its application in research. Its basic qualities (sensitivity,
      specificity and quickness) also offer facilities for its application to the
      detection and amplification of foreign and aberrant genes. Recent reports have
      already shown its ability to detect microorganisms and to identify genes related
      to molecular diseases. Therefore, its application to the diagnosis of infectious
      and genetic diseases is expected in the next future. However, some problems have
      to be solved before the use of this technology is routine in clinical chemistry.

PMID- 7574270
TI  - [Synthesis and pharmacological study of adamantyl benzene propanamines and
      propenamines].
AB  - gamma-(1-Adamantyl)benzenepropanamines and gamma-(1-adamantyl)benzene-beta
      propenamines were synthesized and their pharmacological action was studied on
      mice. Behavioral effects obtained with these compounds and specially the study of
      convulsions, induced by these derivatives, could show a rise of the gamma-(1
      adamantyl)benzenepropanamine's antinicotinic component, which is characteristic
      of all the adamantanamines. On the contrary gamma-(1-adamantyl)benzene-beta
      propenamine's molecular torsion, induced by the double bond, coudl confer to
      these derivatives agonistic properties on the central nicotinic receptor sites.

PMID- 7574271
TI  - [Efficacy of the granisetron/solumedrol combination in the control of drug
      induced acute nausea and vomiting. Results of a prospective survey].
AB  - 5 HT3 antagonist are effective drugs to control chemotherapy induced nausea and
      vomiting, but their optimum utilisation remain to be codify. In order to estimate
      efficacity of granisetron and solumedrol and to improve predictive factors of
      failure of antiserotoninergic agents, a prospective study have been realised 41
      patients. During the first course of chemotherapy, 83% of patients presented less
      than two nausea and vomiting per day. Those results were the same from the first
      to the last course of chemotherapy. This study allowed to estimate anxiety of
      patients and maintain the hypothesis that more a antiemetic regimen is efficient
      less the predictive factors have a prognosis value.

PMID- 7574272
TI  - [Psychopharmacological properties of three magnesium salts: pidolate, lactate and
      aspartate].
AB  - The psychopharmacological activities of three organic magnesium salts were
      estimated on the spontaneous and amphetamine-induced motility, the barbital
      induced sleep and the NMDA toxicity of Swiss mice fed with a normal diet, rich in
      magnesium. Magnesium aspartate had a stimulant effect whereas lactate did not
      clearly modify the animal behaviour and pidolate induced a clear cut
      neurosedative effect. None of these salts afforded protection against NMDA
      toxicity, moreover, aspartate and lactate increased NMDA toxicity. These results
      indicate that depending on the anion, magnesium salts do not have the same
      psychopharmacological activities and that pidolate only seems to respect and
      enhance magnesium basic pharmacological properties.

PMID- 7574273
TI  - [The European Union and drugs].
AB  - 1993 is a mythical year for the European Union which symbolizes at once the
      Achievement of the Internal market and the entry into force of Treaties of Policy
      and Economic Union. The European Union makes up, in all respects, a New Deal for
      Medicinal Products. Indeed, the scientific and technical harmonization is
      realized now at international level (ICH); the broader community competencies in
      the fields of Research, Industrial Policy and Environment predict a new positive
      context for innovation industry and competition probably in accordance with the
      European Agency. A contrario, the recognition of competences of Member States due
      to subsidiary in the following matters: Public Health, Social Security allow some
      flexibility in the interests of consumers, differences being explained by social
      and cultural behaviour in each Member State.

PMID- 7574274
TI  - [Effects of pooling biological specimens on the results of medical biological
      analysis].
AB  - The reasons of pooling biological specimens and the consequences of this approach
      are presented here. Pools are used to prepare lots of control sera or of
      reference solutions. Specimens are also mixed in order to detect some analytical
      interferences. Pooling of biological specimens from several subjects and analysis
      of this pool instead of the measurement of each specimen is not acceptable
      because it induces a dilution of the specimen to be assayed and thus potentially
      false negative results. Another aspect is that dilution is performed with
      specimens of unknown composition. Particularly, these specimens may contain
      interferent substances, inducing analytical errors. These arguments are relevant
      in the different sciences of medical biology and for qualitative and quantitative
      tests.

PMID- 7574275
TI  - Treatment of thumb ulnar collateral ligament ruptures with the Mitek bone anchor.
AB  - Complete thumb ulnar collateral ligament (UCL) injuries usually require primary
      repair. The ulnar collateral ligament is often torn from its insertion site and
      reattachment is difficult. Seven patients underwent repair with the Mitek bone
      anchor (Mitek Surgical Products, Norwood, MA) for complete ulnar collateral
      ligament disruptions. A Stener lesion was found in four patients. Follow-up
      examination was at approximately 1 year. All patients regained a stable
      metacarpophalangeal joint to valgus stress. X-ray films demonstrated accurate
      placement of the bone anchor with protraction of the metallic wings within
      cancellous bone. Range of motion revealed a 7% loss of metacarpophalangeal
      flexion-extension and a 21% loss of interphalangeal motion. Pinch strength in
      apposition averaged 98% and in opposition 97% of the uninvolved hand. Grip
      strength was 96% of the contralateral extremity.

PMID- 7574276
TI  - Stenosing tenosynovitis of the extensor carpi ulnaris.
AB  - Despite the paucity of reports in the literature, we have found extensor carpi
      ulnaris tenosynovitis to be relatively common in our practice. A retrospective
      review of charts revealed 15 patients treated over the last 4 years. Follow-up
      ranged from 10 to 14 months. All patients had ulnar-sided wrist pain and
      underwent conservative treatment consisting of splinting and steroid injection.
      In 7 of the 15 initial treatment failed and surgical release was required. Of
      these, 3 exhibited partially ruptured tendons from exposed bone and underwent
      reconstruction of the floor of the compartment. Preoperative x-ray films were
      helpful in identifying those with bone involvement. All but one patient had a
      good or excellent result. Stenosing tenosynovitis of the extensor carpi ulnaris
      may be more common than reported, and early intervention may prevent tendon
      damage in some patients.

PMID- 7574277
TI  - Graft-versus-host disease in extremity transplantation: digital image analysis of
      bone marrow in situ.
AB  - The development of either unstable immune chimerism and lethal graft-versus-host
      disease or stable immune chimerism and alloimmune tolerance can result from
      extremity transplantation. LBN rats served as recipients of Lewis vascularized
      extremity (limb) transplants. Recipients received no immune suppression and were
      immunologically unmodified. The bone marrow of transplanted and contralateral
      limbs was analyzed in situ for distribution of nuclei, nuclear area, and staining
      intensity by digital image analysis and computerized morphometry. Cellularity was
      significantly increased, and fat content was significantly decreased in the graft
      versus-host disease animals' marrow versus the tolerant animals' marrow for both
      the transplanted and contralateral limbs. Tolerant animals demonstrated
      significantly increased nuclear staining compared with graft-versus-host disease
      animals for both transplanted and contralateral limbs. Additionally, there were
      significant changes between the host and the transplanted limbs for marrow
      intensity and cellularity within tolerant and graft-versus-host disease groups.
      The significant differences in the graft-versus-host disease-positive recipients
      suggested that both autoimmune dysregulation and alloimmune reactions were in
      effect for both donor and host bone marrow compartments. Cellular alterations in
      the tolerant recipients' marrow were suggestive of subtle subclinical graft
      versus-host responses.

PMID- 7574278
TI  - Nosocomial phaeomycotic cyst of the hand.
AB  - We present the case of an elderly man with chronic obstructive pulmonary disease
      who had a 4-month history of multiple fluctuant masses of the dorsum of the right
      hand, which began at the site of an intravenous catheter. Medications included
      inhaled and oral steroids. Fungal cultures of the fluid obtained grew a pigmented
      mold identified as Exophiala species after several routine cultures were reported
      as negative. The patient underwent radical excision of the masses and received a
      perioperative course of oral itraconazole. This is one of the first known cases
      of a possible nosocomially acquired phaeomycotic cyst. Unusual fungi should be
      considered in the differential diagnosis of skin lesions in immunocompromised
      patients.

PMID- 7574279
TI  - Active traction splinting for proximal interphalangeal joint injuries.
AB  - Proximal interphalangeal joint injuries can severely affect hand function. Early,
      active motion is important in ensuring a good range of motion and a functional
      outcome. Active traction splinting is a dynamic splinting system that can be
      performed with either open or closed reduction of phalangeal joint fractures,
      especially at the proximal interphalangeal level. This system allows for
      continued traction on the involved joint and thereby aids in providing a dynamic
      force that will unload the joint throughout its arc of motion and noticeably
      decrease pain. Early, active therapy and the continual in-line traction enables
      the patient to achieve an almost full range of motion early in the course of
      rehabilitation. This combination contributes significantly to improve patient
      understanding and compliance. The benefits of the active traction system are
      reduction of fragments, marked decrease in pain, and early range of motion with
      improved patient compliance. Early, active motion facilitates improved joint
      nutrition, contouring, and healing. Active traction splinting for proximal
      interphalangeal joint injuries is a relatively simple and effective method for
      treating these complex injuries.

PMID- 7574280
TI  - Prospective, randomized trial of splinting after carpal tunnel release.
AB  - To determine the possible beneficial effect of postoperative splint
      immobilization after open carpal tunnel release, we performed a prospective,
      randomized study comparing 2 weeks of postoperative wrist splinting versus a
      bulky dressing only. Forty patients with 43 carpal tunnel releases were
      evaluated. There were no statistically significant differences between the two
      groups using subjective parameters of patient satisfaction with their outcome and
      objective parameters of grip and lateral pinch strength, complication rates, and
      digital and wrist range of motion. No clinical evidence of bowstringing could be
      noted in either group of patients. We found no beneficial effect from
      postoperative splinting after open carpal tunnel release when compared to a bulky
      dressing alone.

PMID- 7574281
TI  - Cutaneous distribution of the ulnar nerve in the palm: does it cross the incision
      used in carpal tunnel release?
AB  - An anatomical study was performed on the ulnar nerve to determine whether
      branches are present in the region of the incision for open or endoscopic carpal
      tunnel release that may be transected or traumatized, resulting in painful
      neuromata or dysesthetic symptoms. Twenty-four cadaveric forearms were dissected
      under 3.5-loupe magnification. A palmar cutaneous branch of the ulnar nerve was
      found in 42% of the limbs. Branches of the nerve were found in the proximity of
      the incision for carpal tunnel release in 12.5%. The palmar cutaneous branch of
      the median nerve was present in 92% of the limbs, with 8% having a branch in
      proximity to the incision. These anatomical findings suggest that injury to the
      palmar cutaneous branch of the ulnar nerve may be responsible for the "painful
      scar" more often than the palmar cutaneous branch of the median nerve.

PMID- 7574282
TI  - Serratus anterior intercostal nerve graft: a new vascularized nerve graft.
AB  - We present our investigative and clinical experience with a new vascularized
      nerve graft: the serratus anterior intercostal nerve graft. The serratus branch
      of the thoracodorsal arterial system was injected with silicone rubber injection
      compound in seven fresh cadavers (N = 11 injected specimens) after the composite
      serratus-intercostal structures were harvested. Microdissection of selected
      vascular territories was then performed. Our findings reconfirmed the previously
      described vascular connections between the thoracodorsal system and the
      intercostal vessels via periosteal vessels. We also newly discovered vascular
      anastomoses between the serratus anterior muscle and the intercostal artery
      running within a mesentery. This mesentery is lateral to and distinct from the
      serratus-periosteal-intercostal network. The nerve graft was applied clinically
      in the reconstruction of a complex soft-tissue, 13-cm ulnar nerve defect of the
      volar forearm after an electrical injury. The clinical application was successful
      with limb salvage and return of protective sensation at 4 months. Our clinical
      and investigative results support the feasibility of the serratus anterior
      intercostal nerve graft, a unique and versatile new vascularized nerve graft.

PMID- 7574283
TI  - Importance of crossover innervation in digital nerve repair demonstrated by nerve
      isolation technique.
AB  - This study was conducted to determine how testing of nerve repair using nerve
      isolation techniques compares with standard testing. Nerve isolation consisted of
      double-gloving, leaving the study finger free, and administering local anesthetic
      blocks to all other sensory contributions in the exposed digit. Ten patients with
      13 single digital nerve repairs of equally severe injuries were studied at a mean
      of 41 months postoperatively. Standardized tests yielded an excellent result in
      77% for static two-point discrimination (S2pd), 85% for moving two-point
      discrimination (M2pd), and 46.2% for Semmes-Weinstein monofilaments (SWMF). The
      same studies combined with nerve isolation yielded an excellent result in only
      43% for S2pd, 43% for M2pd, and 0% for SWMF. These results indicate a
      statistically significant difference and the importance of crossover innervation
      from intact nerves in the long-term result of digital nerve repair. Nerve
      isolation study techniques are an important adjunct in assessing the outcome of
      nerve repair and are the only method of evaluating the true end result of nerve
      regeneration following neurorrhaphy.

PMID- 7574284
TI  - Digital nerve repair: relationship between severity of injury and sensibility
      recovery.
AB  - The purpose of this study was to measure the relationship between severity of
      injury and sensibility outcome. This was done by a retrospective study of 37
      digital nerve repairs in 26 patients, with a mean follow-up of 35 months. All
      patients underwent complete hand examination and standard nerve testing,
      including static and moving two-point discrimination, Semmes-Weinstein
      monofilaments (SWMF), object recognition, and the pick-up test. A hand injury
      severity scoring system based on wound characteristics, mechanism of injury, and
      number of structures involved was then developed. Severity grading led to three
      classes, and each study group was well matched. Subjectively, all patients
      considered their outcome as either good or excellent. Objective results are
      reviewed individually for each test, with the overall combined result of static
      and moving two-point discrimination being excellent (Highet S4) in 81% for class
      I, 41% for class II, and 31% for class III, all different at a statistically
      significant level. We concluded that the severity of injury in the hand can be
      graded and does have a relationship to the functional end result of digital nerve
      repair.

PMID- 7574285
TI  - "Press test" for office diagnosis of triangular fibrocartilage complex tears of
      the wrist.
AB  - We present a simple provocative diagnostic office test for detection of
      triangular fibrocartilage complex tears of the wrist. Twenty-seven patients with
      a working diagnosis of a triangular fibrocartilage complex tear complained of
      wrist pain caused by forceful use; 18 had a history of trauma. A "press test" was
      performed in each, requiring the seated patient to push the body weight up off a
      chair using the affected wrist, creating an axial ulnar load. A positive test
      provoked focal ulnar wrist pain replicating the discomfort that had prompted the
      patient to seek medical attention. Thirteen patients improved with conservative
      treatment. Seventeen underwent magnetic resonance imaging (showing 13 tears and 4
      normal results) and two patients had arthrograms (both had tears). Fourteen
      patients had wrist arthroscopy; all had triangular fibrocartilage complex tears,
      which were debrided, with postoperative clinical improvement. As verified by
      arthroscopy, the press test had 100% sensitivity in preoperative tear detection
      compared with 79% for magnetic resonance imaging. The press test is recommended
      as a useful, free, noninvasive clinical test for triangular fibrocartilage
      complex tears of the wrist.

PMID- 7574286
TI  - Complications of 50 consecutive limited wrist fusions by a single surgeon.
AB  - Fifty limited wrist fusions were performed in 47 patients including 24 scaphoid
      trapezium-trapezoid, 12 capitate-lunate-triquetrum-hamate, and 13 other limited
      wrist fusion combinations. Fusions were performed most commonly for rotary
      subluxation of the scaphoid and follow-up averaged 13.6 months for the chart
      review and 44 months for the questionnaire. There were 10 major complications in
      8 patients, most of which required secondary surgery. There were 3 partial
      nonunions but no complete nonunions. Two patients later underwent a total wrist
      fusion. There were 15 minor complications in 10 patients, most of which were
      managed nonoperatively. A questionnaire was returned on 28 of the 50 fusions.
      Pain levels decreased from a preoperative level of 8.2 to a postoperative level
      of 3.0 (scale of 1-10 with 10 being most severe pain ever). All but 3 patients
      would have the fusion again.

PMID- 7574287
TI  - New dorsal capsulotomy for the surgical exposure of the wrist.
AB  - A reliable, safe approach to the wrist through fiber-splitting dorsal
      capsulotomies has been developed. The dorsal wrist capsule is exposed by
      subperiosteally elevating the fourth and fifth extensor compartments ulnarly and
      translocating the extensor pollicis longus tendon with the radial wrist extensor
      tendons radially. The midcarpal joint and the radial half of the radiocarpal
      joint are exposed by longitudinally splitting the dorsal radiocarpal and dorsal
      intercarpal ligaments, with the apex at the triquetrum. The flap created is
      elevated radially, detaching the dorsal capsule from the radius to the level of
      the styloid process. For exposure of the ulnocarpal joint, the dorsal radiocarpal
      ligament is split longitudinally, and the capsule is incised along the extensor
      carpi ulnaris tendon subsheath proximally to the level of the triangular
      fibrocartilage, with the apex at the triquetrum. The flap created is elevated
      proximally. Exposure of the wrist is excellent, stability of the carpal bones is
      maintained, and closure is simplified using this approach.

PMID- 7574288
TI  - Comparative biomechanical stability of titanium bone fixation systems in
      metacarpal fractures.
AB  - The biomechanical properties of apex bending and torsional rigidity of 11
      different titanium mini- and microplates (Leibinger and Synthes) were examined to
      evaluate the effects of plate design and thickness and screw size and design. Two
      hundred sixteen fresh-frozen human cadaveric metacarpal bones underwent a
      midshaft transverse osteotomy followed by application of one of the following
      plates: Synthes 1.5-mm and 2.0-mm five-hole linear plates; Leibinger linear 1.2
      mm 5-hole, 1.7-mm 4-hole, 2.3-mm 4-hole plates; or Leibinger three-dimensional
      1.2-mm 4-hole, 1.2-mm 8-hole, 1.7-mm 4-hole, 1.7-mm 8-hole, 2.3-mm 4-hole, and
      2.3-mm 8-hole plates. The specimens were subjected to a three-point bending test
      with apex dorsal or apex volar loading or torsional loading. Analysis of variance
      statistical analysis revealed that increasing plate thickness and, more
      significantly, three-dimensional design were associated with increased rigidity.

PMID- 7574289
TI  - Acute adverse effects of blunt adventitial stripping.
AB  - The adventitia is routinely removed from small arteries before the anastomosis,
      but the microcirculatory response to this maneuver has not been documented. We
      have used a rat cremaster muscle flap model for intravital microscopy to compare
      at the microcirculatory level the effect of blunt (n = 18) and sharp (n = 18)
      adventitial removal with unmanipulated control arteries (n = 18). Blunt stripping
      resulted in transient but significant reductions in the red cell velocity (50%, p
      < 0.05) and capillary perfusion (91%, p < 0.05). Sharp dissection did not affect
      red cell velocity; however, capillary perfusion was transiently reduced by 25% (p
      < 0.05). In this study, sharp adventitial dissection was found to be a less
      harmful method of small arteries preparation for microvascular anastomosis.

PMID- 7574290
TI  - Intraosseous wiring in toe-to-hand transplantation.
AB  - Although there are many reports on bony fixations in finger replantations,
      information pertaining to fixation methods in toe-to-hand transplantations is
      scarce. The results of intraosseous wiring were evaluated in 68 toe-to-hand
      transplantations in 47 patients. Clinical and radiological evaluation of bony
      union was conducted an average of 30 months after the procedure. There was no
      malunion. There was one painless pseudarthrosis, with an overall nonunion rate of
      1.5%. Intraosseous wiring is a simple, quick, dependable, and consistent method
      of fixation in toe-to-hand transplantation.

PMID- 7574291
TI  - Brachioradialis muscle flap: clinical anatomy and use in soft-tissue
      reconstruction of the elbow.
AB  - A detailed gross anatomical dissection of 53 upper extremities was performed to
      define the muscular and vascular anatomy of the brachioradialis muscle and to
      evaluate its arc of rotation with specific examination of its usefulness in
      covering soft-tissue defects of the elbow region. A consistent vascular anatomy
      was delineated, with a major pedicle found each time near the elbow arising (in
      descending order of frequency) from the radial recurrent, radial, and brachial
      arteries. A variable number of minor pedicles were found throughout the muscle's
      length. Pedicled proximally, the distal muscle could cover the elbow both
      anteriorly and posteriorly in each case; the proximal portion of the muscle
      (distally pedicled flap) could cover the anterior elbow consistently (100%) as
      well as the posterior elbow (in 91% of dissections). The muscle's arc of rotation
      encompasses the distal half of the arm and the proximal two thirds of the
      forearm, with a consistent ability to cover defects of up to 3 cm in the elbow
      region. Our studies confirm a consistent and robust vascular anatomy as well as
      an arc of rotation that allows predictable coverage of elbow defects in a one
      stage procedure with minimal morbidity, no loss of upper extremity function, and
      no need to sacrifice the major vessels of the upper extremity.

PMID- 7574292
TI  - Reverse neurovascular homodigital island flap.
AB  - We describe a homodigital island flap with a reverse vascular pedicle based on
      the anastomoses between the radial and ulnar digital arteries. These anastomotic
      branches lie between the posterior wall of the tendon sheath and the periosteum
      to form the three digitopalmar arches. The vascularization of the reverse
      homodigital island flap is obtained using the middle transverse palmar arch. This
      flap was performed in 11 patients as a neurovascular "sensitive" flap, including
      the digital nerve in the pedicle, which was then sutured to the contralateral one
      at the defect. This technique achieves cover of the tactile pad in one operative
      stage and provides well-vascularized skin, allowing early mobilization. The
      quality of skin cover was confirmed in all the patients at follow-up ranging from
      7 to 43 months postoperatively. We believe that the benefits of the procedure
      outweigh the disadvantages related to the section of the digital nerve and
      artery.

PMID- 7574293
TI  - First web space release with the dorsal hand rotation flap: closing the donor
      site.
AB  - Release of first web space contractures with the dorsal hand rotation flap
      depends on the mobilization of relatively large areas of skin. Fortunately, the
      dorsum of the hand has sufficient laxity to accommodate such substantial flaps.
      Closure of the resultant donor site may be challenging. Skin grafting over
      extensor paratenon requires prolonged immobilization and is often cosmetically
      unsatisfactory. The purpose of this report is to demonstrate various methods of
      closing these donor sites without skin grafting. We report a series of first web
      space contractures, all of which we released using the dorsal hand rotation flap.
      In closing the donor sites, we demonstrate the utility of advancing local tissues
      as well as bilobed rotational flaps. Our series shows that skin grafting is not
      necessary in the majority of patients. We expect that our results will encourage
      the use of the dorsal hand rotation flap because it yields both functionally and
      cosmetically acceptable results.

PMID- 7574294
TI  - Radial polydactyly: an outcome study.
AB  - Radial polydactyly is a relatively common congenital disorder that frequently
      occurs as thumb duplication. A paucity of information exists on outcomes of
      Bilhaut-Cloquet procedures. To evaluate clinical outcomes, the results of various
      operative and nonoperative treatments were reviewed. Follow-up by retrospective
      chart review was performed on 21 patients treated between 1979 and 1994 at the
      Shriners Hospital for Crippled Children in Erie, Pennsylvania. Patient interview
      or physical examination, or both, was performed on 16 of these patients. The
      study was comprised of 9 boys and 12 girls (average age, 7.8 years; range, 1.5
      15.8 years) and included 26 thumbs. Ablation alone was performed in 6 thumbs (6
      patients), a combined procedure consisting of ablation with radial collateral
      ligament reconstruction and shaving of the metacarpal in 10 thumbs (9 patients),
      and a Bilhaut-Cloquet procedure in 5 thumbs (4 patients). Five thumbs (4
      patients) with Wassel type I classification were managed without surgical
      intervention and simply observed. Of the 6 thumbs treated with ablation alone, 5
      required subsequent procedures (radial collateral ligament reconstruction).
      Ablation with collateral ligament reconstruction and articular surface shaving
      improved clinical alignment and stability but did not return normal
      interphalangeal joint motion. The Bilhaut-Cloquet procedure improved the overall
      cosmetic and functional appearance but likewise did not restore normal joint
      motion. Our findings support current literature that finds that ablation of the
      thumb without reconstruction is contraindicated because of the high reoperation
      rate. Although techniques have evolved that improve alignment and stability or
      appearance, none guarantee normal joint motion. All patients were satisfied,
      however, that the thumb was significantly improved compared with the preoperative
      condition.

PMID- 7574295
TI  - Management of the unbalanced wrist in cerebral palsy by tendon transfer.
AB  - Over a 25-year period, 60 children with spasticity of the upper extremity mainly
      resulting from cerebral palsy underwent surgical reconstruction of the unbalanced
      wrist. A detailed classification of the deformity is described on the basis of
      the functional anatomy of the unbalanced wrist in cerebral palsy, which was
      divided into three groups. In retrospective analysis of the long-term results,
      this classification has proved helpful in selecting an option for the treatment
      of this difficult deformity. In addition, the described classification has aided
      us in keeping accurate follow-up records in predicting the progress of the
      patient, and in coordinating the postoperative treatment.

PMID- 7574296
TI  - Mesenchymal commitment to digital joint formation.
AB  - Temporal and spatial commitment of in vivo and in vitro mammalian digital joint
      development were characterized in a murine model. Alcian blue and alizarin red
      staining were used to label proteoglycans of cartilage matrix and mineralized
      matrix in both whole mounts and histological sections. Mesenchymal
      differentiation toward a joint fate was identified by a lack of matrix deposition
      in islands of joint precursor cells between phalangeal precursors, and localized
      lysosomal enzyme activity was later demonstrated in these regions during
      formation of the joint cavity. Organ-cultured forelimbs and in vivo specimens
      demonstrated analogous digital joint morphological trends. With a defined
      developmental window, reverse transcription, polymerase chain reaction,
      demonstrated differential gene expression of transforming growth factor-beta
      isotypes, aggrecan core protein, and type II collagen, suggesting a role for
      transforming growth factor-beta in directing digital joint development.

PMID- 7574297
TI  - Research in orthopaedic training: the trainees' experience.
AB  - Although a higher surgical degree is considered de rigeur for trainees aspiring
      to the senior registrar grade in general surgery (2,7,4) the same does not appear
      to be true of orthopaedic surgery. Fifty of 51 registrars and senior registrars
      in orthopaedic surgery in the North East Thames Region completed a carefully
      structured and confidential questionnaire which focused on two major aspects. For
      those who had not undertaken a period in full time research, questions examined
      future intentions in this area, and the reasons for those intentions. For those
      who had completed such a period, particular attention was paid to assessing the
      trainees' views of the educational experience, the value of this experience and
      the level of supervision received. Registrars and senior registrars are in a
      phase of training generally referred to as higher training. The majority (56 per
      cent) of higher orthopaedic trainees (HTs) do not expect to undertake a period of
      full time research. This is in stark contrast to the situation in general surgery
      (7). Fourteen of the 50 HTs (28 per cent) had completed a mean of 9.7 months, and
      8 (16 per cent) indicated an intention to take such an opportunity, should it
      arise. For this latter group, the greatest stimulus to this type of work was a
      specific interest in a certain field, followed by a belief that time spent in
      full-time research is of value as an end in itself. For those who had been in
      such a post, a high level of satisfaction in the level of supervision was
      demonstrated. Two important conclusions arise. For the orthopaedic trainee full
      time research is considered a positive choice rather than a hurdle. Trainees also
      feel they are well supervised and find the exposure to research stimulating and
      satisfying. This is in clear contrast with the experience of those in general
      surgery.

PMID- 7574298
TI  - Residency experienced--in pursuit of structured apprenticeship....
AB  - British surgical training is currently undergoing an upheaval. The introduction
      of Higher Surgical Training (HST) as a continuum to the consultant grade will
      have wide implications. I recently undertook a year as a resident in general
      surgery at the Beth Israel Hospital, Boston, USA; in lieu of a second year as an
      SHO in the UK. This paper compares the American Residency system with that
      evolving in Britain.

PMID- 7574299
TI  - Training for vascular surgery: a template for the future.
AB  - Training in vascular surgery is inevitably going to change radically over the
      next few years and we no longer have the luxury of an apprenticeship where the
      trainee matures and develops by prolonged contact with patients and senior
      colleagues. The EEC and Department of Health are insisting on a more focused
      training, by reducing the hours to 72 per week and suggesting accreditation as a
      surgical specialist after six years in higher surgical training. These goals,
      which have already been accepted by the Royal Colleges (and have been welcomed by
      the trainees), will inevitably lead to an entirely different approach to
      training, offering vascular surgeons an opportunity to develop coherent and more
      uniform programmes. To date many trainees have complained that their experience
      has been patchy, and sometimes poorly supervised. The task of developing a
      practical scheme is daunting, but we must start with the patient. Clearly, the
      patients' needs come first so that the training programme must lock on to the
      best standards of care. Only in this way can we ensure that the trainee is
      exposed to the best practice and modern techniques.

PMID- 7574300
TI  - Who should see orthopaedic outpatients--physiotherapists or surgeons?
AB  - Orthopaedic outpatient waiting lists are long and the majority of referrals are
      for conditions that do not respond to surgical intervention. Many of these
      patients are best managed by physiotherapy, orthotics or steroid injections,
      which can be administered by an appropriately trained physiotherapist. The
      effectiveness of a physiotherapist with extended training in orthotics and
      steroid injection was compared with staff grade orthopaedic surgeons in the
      management of orthopaedic outpatients judged unlikely to require surgery from the
      general practitioner's referral letter. Some 221 patients with mechanical low
      back pain and foot and shoulder disorders were seen by a physiotherapist and 97
      by staff grade surgeons over a 10-month period. Outcome was assessed by postal
      questionnaire or telephone contact 6-12 months following discharge. Outcome was
      satisfactory in 80 per cent of patients overall, 65 per cent of low back and 69
      per cent of neck pain, 80 per cent of foot and 83 per cent of shoulder disorders.
      An appropriately trained physiotherapist is as effective as staff grade surgeons
      in managing orthopaedic outpatients unlikely to benefit from surgical
      intervention. This has implications both in reduction of outpatient waiting lists
      and hospital doctor hours of work.

PMID- 7574301
TI  - Use of a palmtop pocket computer to produce a customised logbook of surgical
      experience.
AB  - The use of a pocket palmtop computer for the prospective audit of a basic
      surgical trainee's operative experience is described. A powerful yet portable
      system of information storage is shown, which can be used to compile a logbook
      suitable for examinations and career interviews in clinical surgery.

PMID- 7574302
TI  - Stenting for aortic aneurysm: an early report of a minimal access procedure.

PMID- 7574303
TI  - The use and impact of a daily general surgical emergency operating list in a
      district general hospital: a prospective study.
AB  - Daytime emergency operating lists (EOL) have been shown to reduce out-of-hours
      operating but problems with their introduction have been reported. A six-month
      prospective study of EOL and unscheduled operations (USO) was undertaken. Two
      firms use their EOL differently--one including mostly emergencies, the other
      including a number of urgent elective cases. After the introduction of EOL only 9
      per cent of emergency operations were performed after midnight. Including urgent
      elective cases on the EOL allowed full use of available theatre time but meant
      that proportionately more emergency operations were unscheduled. A senior surgeon
      was involved with 75 per cent of EOL and 36 per cent of USO operations, and a
      senior anaesthetist with 52 per cent of EOL and 14 per cent of USO. Senior
      anaesthetic involvement would have been greater if there were more senior staff.
      There had been a marked increase in the number of USO over the four years
      previous to this study. EOL do reduce out-of-hours operating and allow excellent
      supervision and therefore training opportunities. Care must be taken with the
      case mix to balance full use of theatre time with reduction in out-of-hours
      operating.

PMID- 7574304
TI  - Theatre delay for general surgical emergencies: a prospective audit.
AB  - A prospective audit of emergency theatre use for general surgery has been
      undertaken. Two month periods were studied before and after the introduction of a
      fully staffed 24-hour emergency theatre. Data were collected using a proforma
      documenting the time of the decision to operate, the actual time of the operation
      and the reason for and duration of any delay. After the introduction of the
      facility the proportion of procedures performed after midnight fell from 29 cases
      (21.3 per cent) to 7 (6.3 per cent) (p < 0.05). Emergency operating between 0900
      1700 hrs increased from 40 cases (29.4 per cent) to 71 (61.3 per cent) (p <
      0.05). There was no significant difference in the causes of delay between the two
      groups, the commonest being queuing for theatre. However, the length of the delay
      was significantly reduced. That for an appendicectomy was reduced from a median
      of 4 hrs 40 mins (range 30 mins-18 hrs 45 mins) to 1 hr 29 mins (0-6 hrs 30 mins)
      (p < 0.01) and for drainage of abscess from 5 hrs 56 mins (15 mins-20 hrs 30
      mins) to 1 hr 51 mins (0-4 hrs 30 mins) (p < 0.01). There was no significant
      difference in the seniority of the surgeon making the decision to operate. In the
      first part of the audit we identified problems with regard to delay which were
      addressed by the introduction of the emergency theatre. The audit cycle has been
      successfully closed improving the care of general surgical emergencies requiring
      urgent or emergency operations.

PMID- 7574305
TI  - The clinical terms project: its potential for computerised surgical audit.
AB  - Computerised surgical audit requires accurate and detailed clinical information
      on individual patients. This requires a standardised language which can be
      understood and used by both clinicians and computers. The present system of
      classifying patients using OPCS and ICD coding systems does not allow this
      because both are awkward and imprecise. The clinical terms project was set up to
      overcome these problems. Its aim was to develop a complete medical thesaurus of
      terms which medical and paramedical disciplines could use in their own practice.
      To audit activities in general surgery one needs to be able to record diagnostic
      information, operative procedures, investigations, therapeutic actions, non
      operative procedures, etc. Such information needs to be recorded with various
      levels of detail depending on the degree of specialisation of the surgeon
      involved (eg, a general versus a highly specialised surgeon). In addition data
      needs to be cross-mapped to national classification systems (ICD, OPCS). To
      provide the level of clinical detail required it has been found necessary to
      separate terms into a 'main core term' and 'qualifying terms'. This has resulted
      in a shorter but more comprehensive thesaurus of clinical terms which will enable
      rapid and consistent data transfer between different computer systems.

PMID- 7574306
TI  - An audit of orthopaedic training.
AB  - The changing face of clinical practice in general, and of junior doctors'
      expectations in particular, will inevitably alter the length and nature of higher
      training. Greater awareness and tighter control of this will therefore be
      necessary. This analysis of the curricula vitae of 50 orthopaedic surgeons-in
      training who were appointed to senior registrar posts at The Royal National
      Orthopaedic Hospital, has allowed identification of the 'normal' pattern of
      educational achievement against which individuals may now be assessed. This has
      potential wide-ranging educational and financial implications.

PMID- 7574307
TI  - Medical audit: the role of an orthopaedic preoperative clinic.
AB  - OBJECTIVE: To assess the usefulness of an orthopaedic preoperative clinic.
      DESIGN: Observational study of patients who attended the preoperative clinic.
      SUBJECTS: Thirty patients who attended the clinic over a three-month period.
      SETTING: Orthopaedic Outpatient Department. RESULTS: Twelve of the 30 patients
      had their operation postponed as a result of the visit. CONCLUSIONS: The
      existence of a preoperative orthopaedic assessment clinic is justified. Use of
      such a clinic should lead to the cancellation of fewer operations due to the
      patient being unfit for surgery.

PMID- 7574308
TI  - Feasibility study: diploma in surgical science.

PMID- 7574309
TI  - Random recollections: Part 1. Early life, war and west Africa.

PMID- 7574310
TI  - Acute scybalous colonic obstruction and perforation.

PMID- 7574311
TI  - Excision and primary suture of pilonidal sinus.
AB  - Pilonidal sinus is a common disabling condition of young adults. Many different
      operative treatments have been suggested, the ideal treatment is, therefore,
      controversial. As the recurrence rate for the various procedures is similar,
      avoidance of a general anesthetic, minimal inpatient stay, and minimal
      inconvenience and time off work become important considerations. We present our
      experience with excision and primary closure in 46 patients over a 4-year period.
      Half the patients had a general anaesthetic, the other half a spinal anaesthetic.
      Average duration of inpatient stay was 1 day. Early complications (haematoma,
      wound infection, and minor wound breakdown) occurred in 8%. Early pain was less
      of a feature after the use of bupivacaine infiltration at the end of the
      operation. There were 40 patients available for follow-up, with an average of 3
      weeks off work and a recurrence rate of 17.5%. Of these patients, three have had
      the recurrence treated with no further problems.

PMID- 7574312
TI  - Inpatient and post-discharge wound infections in general surgery.
AB  - The wound infection incidence during inpatient stay was compared with the post
      discharge infection incidence for 1 month using audit data and a patient
      questionnaire. The true infection rate was found to be 20% compared with an
      apparent rate of 2.4% (P < 0.001). The study highlights the problems of
      postoperative monitoring in the context of shorter inpatient stays and fewer
      routine outpatient appointments.

PMID- 7574313
TI  - Can preoperative factors predict for residual malignancy after breast biopsy for
      invasive cancer?
AB  - The presence of malignancy at the resection margins of a malignant breast biopsy
      requires difficult therapeutic decisions about whether a re-excision biopsy is
      necessary. The aim of this study was to determine the factors predisposing to the
      involvement of the resection margins in 280 women undergoing breast biopsy for
      invasive malignancy from a single breast screening practice. Resection margins
      were assessed independently by a single pathologist who noted either the presence
      of tumour at the margins of the biopsy specimen or in the shavings taken from the
      biopsy cavity. Resection margin involvement (RMI) occurred in 113 patients.
      Mammographic microcalcification (MM) was seen in 87 women with invasive cancer
      and RMI occurred in 53 (61%) compared with 60/193 invasive cancers without MM (P
      < 0.001). If RMI was present the patients underwent a second procedure to ensure
      complete tumour excision, and 68% of re-excision specimens from tumours with MM
      and 36% of tumours without MM contained residual malignancy (P < 0.005).
      Statistical analysis demonstrated that these observations were independent of
      tumour size, grade, type, and axillary node status. The presence of mammographic
      microcalcification therefore indicates that wider than usual surgical resection
      margins should be taken.

PMID- 7574314
TI  - Normal inspiratory muscle strength is restored more rapidly after laparoscopic
      cholecystectomy.
AB  - Respiratory complications after laparotomy cholecystectomy may result from
      generalised muscle weakness and fatigue, or from reduced respiratory muscle
      function secondary to an upper abdominal incision. In a prospective study we
      compared maximal inspiratory effort (Pimax/mmHg) and dominant hand grip strength
      (kPa) (expressed as a percentage of zero hour value) in patients undergoing open
      cholecystectomy (OC) (n = 12), laparoscopic cholecystectomy (LC) (n = 25) and a
      control group of patients undergoing lower limb surgery (n = 12). Of the 12 OC
      patients, three suffered respiratory complications: two had atelectasis and one a
      chest infection, compared with no such complications in the other two groups (P <
      0.05). Pimax decreased postoperatively in all groups (P < 0.05) and had returned
      to normal by 48 h in the LC and control groups. In contrast, in the OC group
      Pimax fell from 112.5 +/- 17.8 mmHg to as low as 81.3 +/- 16.5 mmHg at 72 h and
      only returned to preoperative levels at 120 h. The hand grip strength fell
      significantly in all groups at 24 h (P < 0.05) but normal levels were achieved
      again by 48 h in all groups, and there was no significant difference in the hand
      grip strength between the groups over the 5 days. These results suggest that
      generalised muscle fatigue after surgery is similar after open and laparoscopic
      cholecystectomy. Open cholecystectomy does, however, cause a more prolonged
      reduction in respiratory muscle function and this is likely to contribute to the
      higher incidence of respiratory complications in this group of patients.

PMID- 7574315
TI  - Open cholecystectomy in the age of the laparoscope.
AB  - We reviewed our experience with open cholecystectomy since laparoscopic
      cholecystectomy became the treatment of choice for symptomatic gallstones. Over a
      3 year period 35 open (6%) and 578 laparoscopic cholecystectomies (94%) were
      performed. Fourteen trainee surgeons performed only 16 open cholecystectomies and
      assisted at 19. The proportion of open cholecystectomies declined through the
      study period. Ten emergency cholecystectomies were performed for empyema,
      gallbladder perforation, severe acute cholecystitis, liver abscess, and
      cholangitis. In 12 patients, laparoscopic surgery was converted to an open
      procedure because of severe inflammation, empyema, dense adhesions, carcinoma of
      the gallbladder, cholecystoduodenal fistula, and perforated small bowel. Ten
      patients underwent open cholecystectomy and bile duct exploration after failure
      to clear duct stones endoscopically, and three patients had Mirizzi's syndrome.
      Open cholecystectomy is infrequently performed giving trainee surgeons little
      experience. However, such cases are occasionally inevitable and laparoscopic
      surgeons need to have the appropriate skills.

PMID- 7574316
TI  - Laparoscopic appendicectomy: a trainee's perspective.
AB  - Minimally invasive surgery is rapidly becoming an integral part of general
      surgery. Many general surgeons have been trained to undertake laparoscopic
      cholecystectomy. It has been recommended that laparoscopic appendicectomy should
      be the training operation for junior surgeons. The aim of our study was to assess
      whether laparoscopic appendicectomy training can safely be introduced to junior
      surgeons in a district general hospital. During the 11 month study period, 27
      laparoscopic and 38 open appendicectomies were performed. The median anaesthetic
      time was 80 min for laparoscopic and 52.5 min for open appendicectomies.
      Laparoscopic appendicectomies cost, on average, 618 pounds and open
      appendicectomies 770 pounds per case. The complication rate between the two
      procedures was equal. We therefore showed that laparoscopic appendicectomy by
      junior surgeons is both safe and cost-effective. Although the registrar did most
      of the laparoscopic appendicectomies, with resultant less operating for the SHO,
      laparoscopic appendicectomy provided the SHO with training in diagnostic
      laparoscopy and laparoscopic dissection. We conclude that basic laparoscopic
      training should be introduced early in surgical training, after which
      laparoscopic appendicectomy is a safe procedure for surgical trainees.

PMID- 7574317
TI  - Clinical studies of human islet transplantation.
AB  - Recent advantages in techniques for the isolation of human pancreatic islets of
      Langerhans have led to the introduction of clinical trials of islet
      transplantation in diabetic patients who are already immunosuppressed because
      they have received a kidney transplant for end-stage renal failure. This paper
      describes the techniques used and the outcome in three diabetic patients who have
      received intraportal islet transplants. The first two patients received islets
      pooled from multiple cadaveric organ donors, the third patient received islets
      from a single well major histocompatibility complex (MHC) matched donor. The
      islet grafts in the first two patients failed rapidly, almost certainly due to
      rejection. The islet graft in the third patient continues to function after 18
      months. Taken together with the worldwide experience, the results of this small
      series suggest that islet transplantation from a single well MHC matched donor
      may be optimal. For this approach to be a realistic option, techniques for islet
      isolation need to be further improved so that large numbers of islets can be
      regularly isolated from a single pancreas. The collagenase digestion phase of the
      islet isolation process is the major limiting factor and this area requires
      further detailed research.

PMID- 7574318
TI  - Evaluation of vascular and metabolic deficiency in patients with large leg
      ulcers.
AB  - A consecutive series of 50 patients with large leg ulcers (surface area > 100
      cm2) were investigated for evidence of arterial, venous and nutritional problems.
      Arterial insufficiency was found in 34%, venous reflux in 50%. A group of eight
      patients had no arterial or venous problem but had serious deficiencies of
      vitamin C and zinc. Arterial bypass was performed successfully in 15 of the 17
      patients with arterial disease. All patients had a mesh split-skin graft. The 25
      with venous incompetence had compression bandaging; in these patients the ulcer
      had healed on discharge but 10 had recurrent ulceration within 6 months. The leg
      ulcers in patients with corrected arterial insufficiency healed significantly
      more rapidly than those with venous incompetence. The ulcers in those with
      nutritional deficiency healed promptly after skin grafting and correction of the
      deficiency. It is important to be aware of arterial insufficiency and nutritional
      deficiency in patients with leg ulcers, as such deficiencies may contribute to
      the non-healing of an apparently straightforward leg ulcer.

PMID- 7574319
TI  - A 5-year audit of outcome of apicectomies carried out in a district general
      hospital.
AB  - Success rates of up to 90% have been claimed for apicectomy. However, the
      conditions that this procedure is carried out under at district general hospitals
      may be at variance with such studies. A 5-year audit of outcome was therefore
      carried out within a district general hospital. It was found that 89% of
      apicected teeth still remained at 5 years. Outcome was not influenced by any of
      the factors examined, and could not be predicted radiographically. Most failures
      occurred after the average postoperative review period of 10.5 months. Patient
      satisfaction with the procedure was high at over 90%. Based on these results it
      was concluded that apicectomy was an effective procedure when carried out by
      staff of all grades within the district general hospital, and that repeated
      follow-up appointments with radiographs over the first postoperative year were
      not useful.

PMID- 7574320
TI  - Free rib graft reconstruction of the mandible: a forgotten option?
AB  - Eleven patients underwent primary mandibular reconstruction following resection
      of a head and neck squamous cell carcinoma. Reconstruction consisted of a free
      rib graft and a pectoralis major myocutaneous flap. One rib graft failed and one
      graft, although successful, required removal during a wider resection for tumour
      recurrence. A further three patients have died since operation, two from tumour
      recurrence and one from unrelated medical causes. Six patients have undergone
      long-term follow-up of between 22 and 78 months with a mean of 51 months. They
      have oral continence, take a normal or semisolid diet, and have satisfactory
      cosmesis. We present the first long-term follow-up of a series of patients
      undergoing mandibular reconstruction with a free rib graft and pectoralis major
      myocutaneous flap.

PMID- 7574321
TI  - Impact of immunodeficiency virus (HIV) on Fournier's gangrene: observations in
      Zambia.
AB  - The results of a prospective study in the University Teaching Hospital, Lusaka,
      Zambia, on the impact of Human Immunodeficiency Virus on the incidence and
      prognosis of Fournier's gangrene is presented; Zambia has been in the grip of an
      HIV epidemic since the early 1980s. A total of 10 patients with an average age of
      32 years was observed during a 14-month period (March 1992-April 1993); eight
      patients had associated HIV infection. A contributory factor to the development
      of Fournier's gangrene was also present in seven patients, of which six involved
      the urinary tract. All patients were managed by early surgical debridement under
      antibiotic cover. Two patients died, only one of whom had associated HIV disease.
      This study has recorded a significant rise in the prevalence of Fournier's
      gangrene in Zambia since the advent of the HIV epidemic. It has also been
      documented that provided aggressive treatment along established lines is
      initiated without delay, the coexisting HIV infection does not adversely affect
      the prognosis of Fournier's gangrene.

PMID- 7574322
TI  - Efficiency in the outpatient department: the lessons from urology.
AB  - To determine the scope for improvements in efficiency in the outpatient
      management of urological patients, a retrospective analysis was undertaken of
      outpatient records from one consultant's practice in a regional teaching
      hospital. Two hundred consecutive patients referred between March and May 1992
      were studied for 1 year after referral. Each outpatient visit was judged to be
      unavoidable or potentially avoidable. Of referrals, 72% were in one of four
      diagnostic categories (bladder outflow obstruction; haematuria; scrotal
      disorders; frequency/dysuria syndromes). Of these patients, 90% were seen only
      once or twice for each episode of illness. Of the visits, 150/347 (42%) were
      potentially avoidable. Patients with suspected bladder outflow obstruction,
      haematuria and scrotal disorders should undergo imaging of the relevant anatomy
      before referral. Patients with haematuria should be referred directly for a
      flexible cystoscopy after imaging. Urologists need to educate general
      practitioners more clearly about the indications for the treatment of scrotal
      swellings in elderly men and mild bladder outflow obstruction in middle-aged men.
      Patients need not be reviewed routinely after transurethral resection of the
      prostate for benign prostatic hypertrophy or after investigations for haematuria
      have revealed no serious abnormality.

PMID- 7574323
TI  - Some clinical aspects of reconstruction for chronic anterior cruciate ligament
      deficiency.
AB  - A total of 250 patients was reviewed 71.8 months (range 49-105 months) after
      anterior cruciate ligament (ACL) reconstruction for disabling instability that
      had not responded to conservative treatment or correction of internal
      derangements. Knees that had undergone previous operation or had damage to other
      ligaments were excluded. Four techniques were used; MacIntosh extra-articular
      lateral substitution alone (n = 18), extra-articular reconstruction plus intra
      articular carbon fibre (n = 29), extra-articular reconstruction plus a free graft
      from the medial third of the patellar tendon (n = 74), or extra-articular
      reconstruction plus a Leeds-Keio prosthesis (n = 129). The knees were assessed 1,
      3 and 6 years after reconstruction using the Lysholm score and clinical
      examination for the anterior drawer, Lachman and pivot shift signs. The mean
      Lysholm score after 6 years was 77.4 (range 31-100) in the extra-articular group;
      74.4 (range 34-100) in the carbon fibre group; 95.4 (range 43-100) in the
      patellar tendon group; and 91.2 (range 45-100) in the Leeds-Keio group. The
      patellar tendon group had the highest scores (P < 0.003). The pivot shift sign
      returned in 39% of the extra-articular group; 48% of the carbon fibre group; 1%
      of the patellar tendon group, and 36% of the Leeds-Keio group. The pivot shift
      returned least often in the patellar tendon group (P < 0.001). There were 44%
      satisfactory results (pivot shift negative and Lysholm score 77 or more) in the
      extra-articular group; 55% in the carbon fibre group; 92% in the patellar tendon
      group; and 60% in the Leeds-Keio group. The patellar tendon group had the most
      satisfactory results(P < 0.001).ACL reconstruction using the medial third of the
      patellar tendon supplemented with a MacIntosh extra-articular reconstruction is a
      reliable technique for correcting chronic instability and allows most patients to
      return to their former level of activity,including professional sport. No support
      could be found for the use of prosthetic ligaments or the arthroscopic placement
      of ACL substitutes.

PMID- 7574324
TI  - Tension-free mesh hernia repair: review of 1098 cases using local anaesthesia in
      a day unit.
AB  - The technical problems, early complications and short-term results of a tension
      free method of 1098 inguinal hernia repairs in 1017 patients have been assessed.
      The operation was conducted under local anaesthesia, and the inguinal canal floor
      was reinforced by a polypropylene mesh. Patients were discharged home the same
      day. There was no mortality, no urinary complications and one case of venous
      thrombosis. There was one recurrence after a primary hernia repair and two
      patients have developed recurrences after repair of a recurrent hernia. The
      overall sepsis rate was 0.9% and 1% of patients had persistent neuralgia. No
      prosthesis required removal. In all, 49.6% of office workers returned to work in
      1 week or less and 61% of manual workers in 2 weeks or less. The major advantages
      of the tension-free mesh repair under local anaesthesia are simplicity,
      substantial cost savings and very low rates of complications.

PMID- 7574325
TI  - Two-layer repair of the transversalis fascia is sufficient for inguinal hernia
      repair.
AB  - The Shouldice four-layer repair is considered to be the gold standard procedure
      for repair of inguinal hernia with low recurrence rates around 1%. Tension-free
      two-layer repair of the transversalis fascia may be all that is required to avoid
      recurrence. We compared the early recurrence rate after two-layer repair of the
      transversalis fascia or the standard four-layer Shouldice technique in a
      randomised study of elective inguinal herniorrhaphy. In 48 patients (53 repairs)
      who had a two-layer transversalis fascia repair, there was one recurrence (2%) in
      the first 12 months after operation, though there was one more recurrence within
      36 months (total 4%). In 39 patients who had a four-layer Shouldice repair (42
      repairs), there was no recurrence at 12 months but at 36 months two recurrences
      (5%) were found. We conclude that a two-layer repair of the transversalis fascia
      is anatomically correct, physiologically sound and can provide equivalent results
      to the standard Shouldice repair for inguinal hernia.

PMID- 7574327
TI  - Split loop colostomy: a modification.

PMID- 7574326
TI  - Adjuvant therapy for pituitary adenomas: the possible role of photodynamic
      therapy.
AB  - Although benign, pituitary adenomas may not always be curable by surgery alone.
      This is usually owing to dural infiltration and the technical problems of removal
      of involved dura in the sellar region. In such circumstances, some form of
      adjuvant therapy may be needed to address residual tumour and forestall
      recurrence. Radiotherapy and drugs, such as bromocriptine or octreotide, although
      effective are far from ideal adjuvant therapies and this has led to the study of
      the effects of photodynamic therapy on pituitary adenomas. It has been shown that
      photodynamic therapy using the photosensitising drugs haematoporphyrin derivative
      and aluminium phthalocyanine is active experimentally against these tumours. This
      could provide another useful weapon to use against these challenging lesions.

PMID- 7574328
TI  - A better gastric lavage tube: a new use for an 'old' drain.

PMID- 7574329
TI  - Bone transmitted patella percussion.

PMID- 7574330
TI  - Avoidable delay in the management of carcinoma of the right colon.

PMID- 7574331
TI  - The trauma team concept and its implementation in a district general hospital.

PMID- 7574332
TI  - The trauma team concept and its implementation in a district general hospital.

PMID- 7574333
TI  - Transduodenal sphincterotomy for stenosing papillitis and massive
      choledocholithiasis after Billroth II gastrectomy.

PMID- 7574334
TI  - Improving exposure and safety at the saphenofemoral junction.

PMID- 7574335
TI  - Improving exposure and safety at the saphenofemoral junction.

PMID- 7574336
TI  - Management of small fragment wounds in war: current research.

PMID- 7574337
TI  - Clinical guidelines on the management of groin hernia in adults.

PMID- 7574338
TI  - How many trainees are needed in general surgery? A computer model to facilitate
      planning.
AB  - As a consequence of the reduction in junior doctors' hours, the intention to
      shorten training and the freedom of Trusts to appoint additional consultants, the
      requirement for trained surgeons has increased sharply. Whether this consultant
      expansion will be sustained, so as to reach the target of one general surgeon to
      30,000 population, is uncertain. To improve the planning of the number of
      trainees in this unstable environment, a computer model has been established for
      the numbers of higher surgical trainees (HSTs) and consultants. Using a series of
      scenarios the model demonstrates that the existing number of HST posts, with a
      six-year duration of training, cannot deliver the intended 1767 consultant posts
      until about 2016. The target can be reached in 2009 by shortening HST to five
      years or by the conversion of visiting registrar posts to career HST; both
      measures combined can achieve the target by 2006. Thus urgent action is needed to
      increase the output of HSTs in general surgery. In view of the uncertain demand
      for additional consultants, the number of trainees, in each year of HST, should
      be monitored frequently. The number entering training may then be adjusted
      appropriately.

PMID- 7574339
TI  - Reading for the CSiG examination: a survey of current journals.
AB  - Preparing for the new Clinical Surgery in General (CSiG) section of the
      Fellowship examination requires the reading of textbooks and surgical journals,
      the taking of mock clinicals and practice vivas. The increasing number of
      journals in the different branches of surgery makes it difficult for trainees to
      keep abreast of the current literature. A survey of surgical journals currently
      available in most postgraduate libraries was performed over a six-month period in
      order to try and identify those journals, or sections of journals, which offered
      most educational benefit for the CSiG candidate. We found that certain journals
      consistently provide excellent reviews and teaching articles and we recommend a
      personal reading list based on this survey.

PMID- 7574340
TI  - Highly specialised training posts in surgery: a review of the Resident Surgical
      Officer (RSO) experience at St Mark's Hospital.

PMID- 7574341
TI  - 'Unseen' on-call workload of a general surgical team.
AB  - Over a four-month period, we assessed the contribution made to the on-call
      workload of a general surgical team, by referrals and assessments of patients who
      had not been admitted under surgical care and were therefore not recorded in
      current audits of general surgical activity--the 'unseen workload'. Up to 5 1/2
      hours per day on-call (mean 101 minutes) was spent assessing these referrals.
      There was a mean number of 3.6 referrals (range 1 to 7). Although 51 percent of
      these referrals were deemed to be non-surgical after assessment, the majority (77
      percent) were believed to be appropriate. The Accident & Emergency Department
      referred 46 per cent of patients with only 7 percent requiring surgical
      management. This study shows that while hours of work are important in assessing
      the workload of a junior doctor on-call, the intensity of the workload is just as
      important in determining the impact on staff. There is a greater workload than
      revealed by audit of just surgical admissions and operations alone.

PMID- 7574342
TI  - A 10-year analysis of case load and weighted workload in a single Health Board.
AB  - This study analysed the general surgical activity in a single Health Board in
      terms of caseload (case counting) and Intermediate Equivalent (IE) workload.
      Endoscopy and surgery performed wholly within the specialist vascular and
      urological units were excluded. Some 180,466 procedures were prospectively
      recorded through the Lothian Surgical Audit over a 10-year period (1983-92). They
      have now been weighted to reflect workload according to the British United
      Provident Association's schedule of procedures. 5,058 (2.8 percent) procedures
      could not be 'matched' and in a further 2,400 (1.4 percent) there was an error in
      the Lothian Surgical Audit code leaving 172,968 operations for analysis. The
      total number of operations (caseload) performed annually fell by 12 percent over
      the 10-year period. This fall was entirely due to a 28 percent decrease in the
      number of minor operations. The total annual IE weighted workload rose by 2.7
      percent for the 10-year period. Analysis by IE workload revealed that the fall in
      minor operations had been compensated for by an increase in complex major
      operations (CMO). The total caseload of CMO had increased from 224 (1.0 percent)
      to 551 (2.9 percent). This represented an increase in the proportion of workload
      from 5.3 percent to 12.45 percent. Thus a 1.9 percent increase in case load
      represented a 7.1 percent increase in IE workload. In the final year major and
      complex major operations formed 24.6 percent of the caseload which represented
      53.2 percent of IE weighted activity. This study suggests that IE workload based
      on the BUPA schedule is a valid and reproducible method of weighting that
      accurately reflects the changing workload of different case mixes. This
      differential must be appreciated to ensure accurate allocation of resources. In
      future surgical activity,including waiting lists,should be assessed by weighted
      workload rather than case numbers.

PMID- 7574343
TI  - SHO surgical training, is the one-day case unit a suitable environment?

PMID- 7574344
TI  - Whither WIST? Women in Surgical Training Scheme.

PMID- 7574345
TI  - Random recollections: Part 2. Penicillin and the Normandy landings.

PMID- 7574346
TI  - [Current treatment of cancers of the anal canal].
AB  - The major development in the treatment of cancers of the anal canal, over recent
      years, is the now predominant role of radiotherapy which has replaced amputation
      surgery as first-line treatment. All stages combined, the average 5-year global
      survival rate is now 60%, with a local control rate of 70% and good sphincter
      preservation in the majority of healed patients. However, many questions remain
      unresolved in these rare cancers: what is the optimal irradiation technique, what
      is the role of chemotherapy in this very chemosensitive tumour but associated
      with a low risk of metastases? Amputation surgery still plays an important role,
      but the exact time at which it should be proposed remains controversial. The rate
      of inguinal lymph node invasion is approximately 20%. The value of systematic
      treatment N0 inguinal nodes remains controversial. As for most problems of
      clinical oncology, only randomized trials rapidly conducted on a large scale will
      be able to provide an answer to all these questions.

PMID- 7574347
TI  - [Therapeutic choices in cancer of the rectum].

PMID- 7574348
TI  - [Value of iliac direct-view retroperitoneoscopy (or "extraperitoneal
      pelvioscopy") in the assessment of lymph node invasion by pelvic cancer].
AB  - Iliac retroperitoneoscopy, also called extraperitoneal pelviscopy (EPP), is a
      form of direct vision endoscopy derived from mediastinoscopy; It allows biopsies
      of pelvic lymph nodes. In view of the poor accuracy of radiological
      investigations for pelvic lymph node metastasis (N+) detection, EPP was performed
      in 210 patients with apparently resectable neoplasms (bladder n = 116, prostate n
      = 81, cervix n = 12, endometrium n = 1). Among 174 patients without radiologic
      evidence of metastasis (N-), EPP assessed 47 N+ patients and failed in 1 case,
      requiring a laparotomy (one N+ patient). Among 36 N+ patients after radiologic
      examinations, EPP assessed 20 N- patients and failed in 1 case, requiring a
      laparotomy (one N+ patient). Among 124 N- patients after EPP, a further
      laparotomy showed 8 N+ cases (false negative). Thus, out of 210 patients, EPP
      corrected the radiologic findings in 67 cases and drastically modified the
      therapeutic indications. Considering its absence of contraindications, EPP can be
      performed more often than laparoscopic pelvic lymphadenectomy techniques.
      Furthermore, its exploration field is not limited to the interiliac area. Its
      overall reliability is 95% in staging lymph node involvement of pelvic neoplasms.

PMID- 7574349
TI  - [Enterovesical fistulas in Crohn disease: diagnosis and treatment].
AB  - Internal fistula is a complication of Crohn's disease. Among 589 patients
      operated upon at Hopital Saint-Antoine between 1970 and 1992, 17 (2.9%) had
      entero-vesical fistula. Ileovesical fistulas were twice as frequent as
      sigmoidovesical fistulas. Typical symptoms were pneumaturia, fecaluria, and
      recurrent urinary tract infection. Cystoscopy was performed in 8 patients and
      determined the site of the fistula in each case. The indication for operation was
      the fistula itself (35%) or another complication of Crohn's disease (65%).
      Associated lesions were as follows: 6 entero-enteral, 2 ileogenital, 5
      enterocutaneous fistulas and 6 intraabdominal abscesses. Resection of the bowel
      segment responsible for the fistula was performed in every case, with primary
      anastomosis in 9 cases and enterostomy in 8 cases. The vesical opening was
      excised and sutured in 10 cases and left open in 7 cases. An urethral catheter
      was left in place for at least 7 days. There was no postoperative death; one
      postoperative external vesical fistula healed without reoperation. Seven
      enterostomies have been closed, one is definitive. There were no late recurrences
      of vesical fistula.

PMID- 7574350
TI  - [Result of surgical treatment of exteriorized rectal prolapse in adults.
      Experience of 21 years].
AB  - Between 1971 and 1992, 89 patients (57 women, 32 men; mean age: 61 years)
      underwent surgical treatment for total rectal prolapse. 68.5% were constipated,
      and 12.3% had a solitary rectal ulcer, 46% were incontinent (3 grades 2, 11
      grades 3, 27 grades 4). Twelve patients (21%) had been previously, but
      unsuccessfully operated. Manometry showed low resting pressures in the upper part
      of the anal canal, particularly in incontinent patients. Voluntary contraction
      was lower in incontinent patients. The resting anorectal angle was obtuse (113
      degrees). Orr-Loygue operation (n = 53), modified rectopexy (n = 22), rectopexy
      to the left inguinal ligament (n = 6), Delorme operation (n = 4), and posterior
      rectopexy (n = 4) were performed. There was no operative mortality.
      Intraoperative and postoperative morbidity rates were 3.4% (n = 3) and 29%.
      Rectal prolapse recurred in 3 cases (3.4%). Solitary rectal ulcer healed in all
      patients. Only 8 patients were incontinent after operation, but control was
      better in 6 cases; in other both patients, preoperative electromyography showed
      grade III denervation. Bowel habit was postoperatively better (68.5% of patients
      were constipated before operation, 51.7% after operation). Resting pressures
      increased in preoperatively incontinent patients in the upper part of the anal
      canal; resting external sphincter pressures always increased. There was no change
      in the resting anorectal angle (112 degrees).

PMID- 7574351
TI  - [Risks of accidental exposure to blood in the operating room. Results of a
      multicenter prospective study. Groupe d'Etude sur les Risques d'Exposition au
      Sang].
AB  - A multicentric prospective trial was conducted to evaluate the frequency and kind
      of blood exposure in operating room. From march to june 1992, 3554 procedures
      were observed in 22 surgical units (visceral, orthopaedic and vascular), with 129
      surgeons, 133 residents and 216 nurses. Statistic analysis was done on Epi Info 5
      (CDC Atlanta) and EGRET (Statistic and Epidemiology Research Corporation,
      Seattle). 11.7% of procedures were the case for an incidental blood exposure:
      4.2% for percutaneous exposure; 8.4% for cutaneous or mucosal exposure. Rates
      change with the surgical specialty. Surgeons were involved in 50.7% of
      percutaneous exposure and 58.7% of the cutaneous or mucosal exposures, especially
      when they were operators (respectively 2 and 5.6% person-act). A significative
      rate was founded between incidental blood exposure and the length of procedure,
      the sepsis character of the procedure, but not with emergency or number of
      globular units transfused. To diminish the incidental blood exposure and its
      risks, this data suggests three kinds of practice: a better work for vaccination;
      in our study 59% of surgeons declare an adequate vaccination against hepatitis B;
      a best operative hygiene, with knowing of risks factor of blood exposure,
      depending of the kind of procedure, changing between different units; the use of
      protections: non coated dressing, double gloving, ocular protection.

PMID- 7574352
TI  - [Biological glue does not reduce lymphorrhoea after lymph node excision.
      Randomized prospective study on 40 patients].
AB  - The aim of this prospective and randomized study, was to demonstrate the benefit
      by using fibrin glue after axillary lymph node dissection. From January 1990 to
      January 1991, forty females were randomized before surgery for breast cancer: 20
      patients of the group A underwent additional application of fibrin glue (5 ml
      containing 500 IU of thrombin) by spray only in the area of axillary dissection,
      while the 20 patients of group B acted as the control group. The two groups were
      compared for age, number of nodes removed and involved, drainage volume and
      duration and complications. Student's t test, Mann and Whitney non parametric
      test and chi 2 were used when appropriate for statistical analysis. The two
      groups were well balanced for age, number of nodes removed and involved, staging
      and histologic findings. The average volume of lymphorrhoea in the lymph node
      dissection area was greater after use of fibrin glue (410.4 ml) than in controls
      (275.5 ml, p = 0.016). No difference was noted between the two groups for the
      volume of drainage of the mastectomy or lumpectomy site or, for the total volume
      of drainage. Drainage durations as well as hospital stay were similar. Six
      complications occurred in group A, and one in group B (p = 0.037).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7574353
TI  - [The gastro-omental flap: a secreting mucous flap for reconstruction of the
      oropharynx and the oral cavity].
AB  - The gastro-omental flap consists of a patch taken from the greater curvature of
      the stomach and the bordering omentum. It is based on the right gastro epiploic
      vessels and is used as a free flap for intraoral reconstruction after resection
      of oral carcinoma. Twenty patients underwent gastro-omental flap. The operative
      technique is described. The evaluation consisted in questioning, chemism on the
      salivary flow and biopsies. There is no morbidity related with the donor site.
      The gastro-omental flap avoids post irradiation xerostomia. Oral irritation and
      bleeding of the flap may occur.

PMID- 7574354
TI  - [Effects of intraperitoneal insufflation on hematogenous seeding of abdominal
      infections. Preliminary results of an experimental study in rats].
AB  - Most laparoscopic procedures require the creation of a pneumoperitoneum. In order
      to evaluate the potential hazards of bacteriemia related to insufflation, we
      conducted a study in the rat. Two groups of 20 Wistar rats were used for this
      study. Peritonitis was induced by opening the terminal ileum. Twenty-four hours
      later, 20 rats were insufflated at a mean pressure of 6 mm Hg (Group I). After
      one hour of insufflation, an hemoculture was performed via direct intracardiac
      puncture and in the other group of 20 non-insufflated rats (Group NI). Five of
      the 18 hemoculture were positive in the Gr. I (27.7%) and 6 out of 20 in the Gr.
      NI (30%) (chi 2 = 0.238 p = 0.62 non significant difference). These results
      suggest that insufflation does not facilitate hematogenous dissemination of
      bacteria from intraperitoneal sepsis in this animal model.

PMID- 7574355
TI  - [Oxidants and antioxidants. Biological effects and therapeutic perspectives].
AB  - The main oxidizing free radicals (FR) are oxygen-derived metabolites (superoxide
      anion O2-, hydrogen peroxide H2O2, hydroxyl radical OH (zero)), hypochloric acid,
      chloramines, nitrogen dioxide, ozone and lipid peroxides. They are produced
      continually by living organisms, either in the intracellular compartment by the
      mitochondrial respiratory chain and mixed function oxidase system, or in the
      extracellular compartment, especially by phagocytes. The body possesses complex
      protective antioxidant systems against this potentially toxic production, such as
      dismutase superoxides, catalase, the glutathione enzyme system, metallic ion
      sequestration, enzymes degrading proteins injured by FR, metabolising
      hydroperoxides, and repairing DNA, and vitamins E, C, P, and betacarotene. A
      physiological steady-state is established under normal conditions between the
      production of oxidants and their neutralization by antioxidants. Oxidative
      lesions result from a disturbance of the oxidant-antioxidant balance. Oxygen
      derived metabolites act on polyunsaturated cell membrane lipids, induce genetic
      alterations, and oxidize sulfhydryl groups of proteins, thereby modifying their
      functions. FR are involved in major physiological mechanisms such as
      phagocytosis, the inflammatory reaction, and the reperfusion ischaemia phenomenon
      observed during organ storage. The therapeutic use of enzymatic (SOD, catalase,
      GSH) and nonenzymatic antioxidants (vitamins E, N-acetylcysteine, allopurinol and
      oxypurinol) has yet to be evaluated. The current state of our knowledge indicates
      the extreme complexity of these systems and calls for caution in the therapeutic
      use of antioxidant substances.

PMID- 7574356
TI  - [Pseudotumoral rectal endometriosis].
AB  - A case of rectal endometriosis, presenting in the form of acute obstruction, is
      described. The primary diagnosis was malignancy, but endometriosis was discovered
      at emergency operation. The diagnosis and management of rectal endometriosis are
      reviewed.

PMID- 7574357
TI  - [Gastric plasma cell granuloma. Apropos of a case].

PMID- 7574358
TI  - [Glomus tumor of the stomach with extraserous development].

PMID- 7574359
TI  - [Pericardial hydatid cysts. Value of magnetic resonance imaging. Apropos of a
      clinical case].
AB  - Cardiac hydatic cysts are rare and represent 0.5 to 2% of all hydatic cysts in
      humans [1, 2]. They are usually found in the left or right ventricle, and
      exceptionally in the interventricular septum. An exclusively pericardia hydatic
      cyst is excessively rare. The case reported here emphasizes: That this hydatid
      cyst of the pericardium remained asymptomatic until rupture. The role of
      echocardiography as a diagnostic tool. The superiority of MRI to CT Scan in the
      establishment of a precise preoperative diagnosis.

PMID- 7574360
TI  - [Brakes and levers of mobilization concerning cardiovascular prevention].
AB  - It is widely known that epidemiological studies have identified several major
      cardiovascular risk factors, such as hypertension, smoking, diabetes mellitus,
      and hypercholesterolaemia. It is also widely known that the management of these
      factors leads to a reduction of cardiovascular morbidity and mortality, and the
      benefit on global mortality has been demonstrated very recently. It is relatively
      easy to ensure effective secondary cardiovascular prevention, as the patients are
      generally fairly motivated, but it is much more difficult to ensure effective
      primary prevention, as the subjects concerned are in good health and need to be
      convinced of the value of preventive measures. Primary prevention must be based
      on better information of patients and physicians, warning them against certain
      denigration campaigns, such as those designed to minimize the role of lipid
      abnormalities in the pathogenesis of atherosclerosis and to falsely reassure our
      countrymen with the famous French paradox. This discussion concerning the
      difficulty and importance of primary cardiovascular prevention concludes with
      several concrete proposals.

PMID- 7574361
TI  - [Experimental models of venous thrombosis].
AB  - Various experimental models have been developed in order to more clearly
      understand deep vein thrombosis, the mechanisms involved and its treatment. These
      models are based on venous stasis, either alone or combined with the injection of
      thrombogenic substances or endothelial lesions. Other models only use endothelial
      lesions. Thrombogenic substances are mostly composed of activated factor X or
      thrombin, which raises the problem of purity of the substances and determination
      of the antithrombotic activities of the substance tested, especially heparin and
      hirudin and their derivatives, and consequently their efficacy. Endothelial
      lesions can be induced by chemical, physical or electrical agents or by repeated
      application of clamps, or cellular crushing. These models result in the formation
      of various forms of venous thrombus. The development and improvement of
      experimental models is very important in every case. Experimental models of
      thrombosis constitute the best tool for the study of thrombosis, in which many
      points remain to be elucidated. They also allow the study and development of
      various antithrombotic substances the improvement of their efficacy. These models
      must be validated, standardized, reproductible and in agreement with local
      legislation in each country.

PMID- 7574362
TI  - Growth factors, tissue and urokinase-type plasminogen activators in venous
      ulcers.
AB  - Bioimmunoassays for tissue and urokinase-type plasminogen activators (t-pA and u
      pA), and enzyme-linked immunosorbent assays (ELISA) for t-pA were performed on
      biopsies from the edge and base of 15 venous ulcers. TGF-beta 1, bFGF and PDGF
      were assessed by ELISA in the edge and base of 19 further venous ulcers and 7
      biopsies of normal skin. The presence of all three growth factors and u-pA was
      confirmed immunohistochemically. T-pA was detected using the ELISA and the
      bioimmunoassay, but was quantified in 3/15 ulcer bases and 4/15 ulcer edges using
      the bioimmunoassay only. U-pA was measured in all ulcer samples except one. TGF
      beta 1 was measured in 13/19 ulcer bases and 9/19 edges, while free TGF-beta 1
      was measured in only 2/19 bases and 4/19 edges. Venous ulcer bases contain
      significantly greater quantities of u-pA, TGF-beta 1, and bFGF than ulcer edges.
      TGF-beta 1 was never detected in normal skin. There is significantly less bFGF in
      normal skin than in venous ulcer bases, but not edges (p = 0.013, p = 0.31
      respectively, Mann Whitney U-test). There was a good correlation between ulcer
      edge TGF-beta 1 and time to healing in ten ulcers that healed within six months
      from the date of biopsy (r = -0.56, p = 0.065, Spearman Rank Correlation). There
      was a significantly greater amount of ulcer edge bFGF in the ulcers that healed
      within six months than those that remained unhealed (p = 0.036, Mann-Whitney U
      test).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574363
TI  - [Evaluation of 3 functional classifications of cardiac insufficiency: a national
      multicenter study. National College of French Cardiologists].
AB  - The scope of this study is a comparison of three functional classifications: the
      New York Heart Association classification, the Duke University classification,
      and the specific activity scale we propose. The NYHA classification is
      subjective, difficult to reproduce and poorly correlated to the functional
      capacity measured ergometrically (duration of exercise and/or VO2). A new
      classification must therefore be proposed. A specific activity scale adapted to
      our national requirements appears to be the best solution. Our study covered 15
      successive days. All patients suffering from congestive heart failure who were
      examined over this period were included. 700 liberal cardiologists took part in
      this study. 2353 patients were reviewed, mean age 69 (58% male, 42% female).
      Heart failure was of an ichaemic origin in 37% of cases, idiopathic in 25% and
      due to hypertension in 25%. Symptomatology was left sided in most cases. Among
      NYHA Class IV patients, 75% belonged to Class IV of the specific activity scale
      (SAS) (23% Class III, 1% Class II), and 88% of the Duke classification (10% Class
      III, 1% Class II). For NYHA Class III patients, 80% were SAS Class III (5% Class
      IV, 13% Class II), and only 38% (42% Class IV and 16% Class II) of the Duke
      classification. Regarding NYHA Class II patients, 74% were SAS Class II (21%
      Class III and 4% Class I), and 26% of the Duke classification (39% Class I, 29%
      Class III and 3.6% Class IV). Finally, among NYHA Class I patients, 60% were SAS
      Class I (34% Class II, 5% Class III), and 74% of the Duke classification (11%
      Class II and 13% Class III).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574364
TI  - [Treatment of aortic aneurysm by endovascular prosthesis: conclusions and
      recommendations of the ANDEM (National Agency for Medical Development and
      Evaluation)].

PMID- 7574365
TI  - Special issue on oesophageal surgery.

PMID- 7574366
TI  - Gastro-oesophageal reflux and oesophageal motility diseases. Who should perform
      antireflux surgery?

PMID- 7574367
TI  - The Mark IV antireflux procedure.

PMID- 7574368
TI  - Nissen fundoplication for gastro-oesophageal reflux disease: long-term results.
AB  - Since its introduction by Rudolph Nissen in 1956, fundoplication has become the
      most commonly used antireflux procedure. Following fundoplication the majority
      (80 to 90%) of the patients become symptomfree or have only mild and occasional
      reflux symptoms in the long run. With a short and loose fundic wrap postoperative
      dysphagia is not a clinical problem, providing that preoperative manometry shows
      adequate peristalsis. Flatus is increased after fundoplication, but rarely to a
      disturbing extent. Patients who have problems with flatus preoperatively are also
      prone to have complaints postoperatively. Bloating is decreased rather than
      increased after fundoplication. At endoscopy as intact seen fundic wrap (the main
      determinant of the long-term outcome) is observed in 70% to 80% of the cases 10
      to 20 years after the operation. Oesophageal 24-hour pH-recording is normal and
      oesophagitis cured in similar number of patients. In conclusion, Nissen
      fundoplication gives effective cure of symptoms of gastro-oesophageal reflux
      disease and reliably corrects reflux oesophagitis. Postoperative adverse effects
      are rare and well tolerable and do not detract from the success of the operation
      in correctly selected patients.

PMID- 7574369
TI  - Reoperations after failed antireflux procedures.
AB  - With the advent of laparoscopic surgery, the number of anti-reflux procedures
      performed has virtually exploded in some centers. Persistent, recurrent or new
      symptoms after an antireflux procedure are therefore likely to become a more
      common problem in the near future. Recurrent reflux is usually due to a breakdown
      of the repair and can frequently be treated medically or by a repeat antireflux
      procedure. In contrast, postoperative dysphagia, with or without accompanying
      reflux symptoms, may be due to a myriad of causes which include a slipped wrap, a
      wrap that has been placed around the stomach rather than the esophagus, a wrap
      which is either too tight or too long, the development of a stricture, the
      presence of a motor disorder of the esophageal body, or a combination of these
      factors. These situations can not usually be solved by a simple redo
      fundoplication or medications. Rather, the successful management of these
      patients requires an individual therapeutic approach, based on the presenting
      symptom or symptom constellation, the results of function tests and the
      intraoperative findings. The surgeon caring for patients with failed antireflux
      procedures should be intimately acquainted with the whole spectrum of revisional,
      resective and reconstructive procedures of the stomach, cardia, and esophagus.

PMID- 7574370
TI  - Laparoscopic and thoracoscopic antireflux surgery.
AB  - Despite new effective drugs, like omeprazole, reducing gastric acid output and
      relieving gastro-oesophageal reflux disease (GERD) symptoms in most patients,
      there are still clear indications for surgical treatment of this chronic disease.
      The main indications are failure to control symptoms by medical treatment,
      noncompliance to medication and development of complications. Recent developments
      in minimal access surgery have modified the surgical approach to the treatment of
      GERD. The antireflux surgical procedures can be endoscopically performed
      reproducing all the essential component steps of the equivalent open operations,
      but with all the advantages of minimal access surgery. The fundoplication
      procedures are mainly performed laparoscopically and the thoracoscopic approach
      is chosen in patients with short oesophagus, morbid obesity or other
      contraindications to the laparoscopic approach. The short-term results of
      endoscopic antireflux surgery are at least as good than after open surgery. A
      review on the laparoscopic and thoracoscopic antireflux procedures is presented.

PMID- 7574371
TI  - Surgical management of Barrett's esophagus.
AB  - Barrett's esophagus is a premalignant metaplastic change in the lining of the
      distal esophagus. It represents a peculiar form of healing which can occur at any
      time in patients with reflux esophagitis. Ninety percent of patients with
      Barrett's esophagus have a mechanically defective lower esophageal sphincter and
      93% have abnormal esophageal acid exposure on 24 hour esophageal pH monitoring.
      Barrett's esophagus should be considered in all patients undergoing endoscopy for
      symptoms of reflux disease and is confirmed when any biopsy shows the presence of
      specialized intestinal metaplasia, irrespective of the macroscopic appearances of
      the distal esophagus. An anti-reflux procedure is indicated for patients with
      Barrett's esophagus since it is highly effective in controlling reflux symptoms,
      healing the associated esophagitis, prevents repetitive injury of the Barrett's
      epithelium, and is more effective than medical therapy in the long term. Annual
      endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is
      indicated after the antireflux repair. Identification of high grade dysplasia
      heralds the development of invasive cancer and offers the surgeon an opportunity
      to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the
      differentiation between high grade dysplasia and invasive adenocarcinoma is
      unreliable. Esophagectomy remains the treatment of choice for patients with high
      grade dysplasia. Barrett's adenocarcinoma can be cured by en bloc esophagectomy
      in selected patients with early disease.

PMID- 7574372
TI  - The Ersta procedure, a hemifundoplication for the treatment of gastro-oesophageal
      reflux disease.
AB  - Symptoms of gastro-oesophageal reflux and gastro-oesophageal reflux disease
      (GERD) are common in the population and are a frequent reason for consulting
      physicians and surgeons. If complications of reflux occur or if the problem
      cannot be managed without medication such as H2 blockers or proton pump
      inhibitors, surgery should be considered. In the majority of cases GERD is caused
      by a surgically correctable anatomical defect affecting the angle of His and the
      flap valve mechanism. Patients should be carefully evaluated prior to surgery,
      and for maintaining good long-term results the antireflux procedure should be
      performed by surgeons with special interest in the field. We present our
      experience with a hemifundoplication performed both by open technique and through
      laparoscopy.

PMID- 7574373
TI  - Manometric vector volume analysis to assess lower esophageal sphincter function.
AB  - The resistance provided by the manometric high pressure zone at the
      gastroesophageal junction, is the major barrier against gastroesophageal reflux
      in man. Recent studies have shown that this high pressure zone has its correlate
      in the architecture of the gastric 'sling' fibres at the gastric notch and the
      semicircular 'clasps' at the lesser curvature side of the gastroesophageal
      junction. Pull-back manometry with radially oriented pressure transducers allows
      to assess these distinct components of the human lower esophageal sphincter. With
      the recent introduction of personal computers into the manometry laboratory,
      three-dimensional manometric images of the lower esophageal sphincter can be
      easily constructed, based on radially oriented pressures. The application of this
      new technology has shown that calculation of the sphincter pressure vector
      volume, i.e. the volume circumscribed by the three-dimensional manometric
      sphincter image, is superior to standard manometric techniques in the assessment
      of lower esophageal sphincter function. The sphincter pressure vector volume is a
      particularly helpful parameter to identify patients with gastroesophageal reflux
      disease who will not benefit from medical therapy and should consequently undergo
      early antireflux surgery. Vector volume analysis is also helpful in assessing the
      cause of recurrent symptoms in patients with previous antireflux surgery. In
      patients with achalasia three-dimensional sphincter imaging and vector volume
      analysis can illustrate a severely asymmetric and hypertensive sphincter and show
      the effect of myotomy with or without a concomitant antireflux procedure on the
      sphincter pressure profile.

PMID- 7574374
TI  - Thoracoscopic and laparoscopic Heller's myotomy in the treatment of esophageal
      achalasia.
AB  - The treatment of esophageal achalasia has been controversial for many years. Even
      if a myotomy performed through a left thoracotomy gives better results than
      pneumatic dilatation, the fear of an operation with the associated postoperative
      pain and disability has kept patients away from this form of treatment. Minimally
      invasive surgery allows the same results obtained with open surgery, with a short
      hospital stay, minimal postoperative discomfort, and a fast recovery time. A
      thoracoscopic or laparoscopic Heller's myotomy should be considered today the
      primary form of treatment for esophageal achalasia.

PMID- 7574375
TI  - Laparoscopic Heller-Dor operation for the treatment of oesophageal achalasia:
      technique and early results.
AB  - From January 1992 to December 1994, a laparoscopic oesophageal myotomy combined
      with Dor fundoplication was performed in 33 patients with oesophageal achalasia.
      Intraoperative endoscopic balloon distension of the cardia proved useful to
      identify the oesophagogastric junction, ease the myotomy, and control its
      completeness. There was no operative mortality. A mucosal tear not requiring
      conversion occurred in three patients who had previously undergone pneumatic
      endoscopic dilations of the cardia. The early clinical and functional results
      show the effectiveness of the operation.

PMID- 7574376
TI  - Endoscopic discision of Zenker's diverticulum.
AB  - Being typically an elderly make, the patient with a Zenker's diverticulum quite
      uncommonly presents in the best condition for surgery. Optimal management should
      therefore minimize the operative risk, shorten the time of postoperative
      hospitalization, and simultaneously avoid postoperative recurrence of the
      disorder. Using an automatic stapling device, the sphincter of the diverticulum
      (consisting mainly of the cricopharyngeus muscle) is cut easily endoscopically,
      with reliable haemostasis and a wide opening of the pouch as result. Six cases
      operated on by us between December 1993 and August 1994, became completely free
      of symptoms. The surgical technique (actually a variety of the traditional
      Dohlman's procedure) is described. Postoperative results over a follow-up of 3-8
      months, and details of one non-serious postoperative complication are reported.
      Our experience of this pilot series gives rise to positive expectations of a new,
      safe, and time-saving procedure for successful treatment of even elderly patients
      with Zenker's diverticulum.

PMID- 7574377
TI  - Surgical management of benign stricture from reflux oesophagitis.
AB  - From January 1976 to December 1994, out of 605 patients with reflux oesophagitis,
      166 (27.4%) presented with an oesophageal stricture, and 68 of these (40.9%)
      underwent surgical therapy. Thirteen of the 68 patients (19.1%) had an associated
      Barrett's oesophagus. Oesophageal manometry revealed scleroderma in nine
      individuals (13.2%). The stricture was undilatable in 11 patients (16.1%)
      observed before 1985. An oesophageal-sparing operation was performed in the
      majority of patients: fundoplication (n = 39), Collis gastroplasty plus
      fundoplication (n = 10), and total duodenal diversion (n = 4). Oesophageal
      resection was performed in 15 patients (22%); 12 of these individuals were
      operated on before 1985. The mortality rate was 4.4%: two patients died of
      necrosis of the interposed colon and one of acute pancreatitis. The average
      follow-up time was 27 months (8-136). Oesophageal-sparing procedures
      significantly reduced the need for further endoscopic dilatation (P < 0.001).
      Standard fundoplication was successful in 30 out of 39 patients (77%). Reasons
      for a failed fundoplication were a long, hard stricture, an ineffective partial
      wrap in patients with unrecognized short oesophagus, or underlying scleroderma.
      Regression of Barrett's mucosa was not recorded with any of the conservative
      surgical procedures.

PMID- 7574378
TI  - Cancer of the oesophagus and gastric cardia. Standard oesophagectomy and
      anastomotic technique.
AB  - We reviewed the operative results of 785 one-stage resections for carcinoma of
      the oesophagus and cardia, out of a total of 1,264 patients with this tumour
      managed over a 12-year period (62%). Resection was considered curative in 321
      patients (41%), and was palliative in 464 patients (59%). Seventy percent of
      patients had operative Stage III disease, while 5% had Stage IV disease. The two
      most frequently performed procedures were the transthoracic Lewis-Tanner
      operation (49%), and the transhiatal oesophagectomy (14%). Our results showed
      comparable operative morbidity, mortality and survival between the two resection
      groups, with the exception of a higher risk of recurrent nerve injury after the
      transhiatal operation (18% versus 9%). The results were based on selection
      criteria favouring patients with increased pulmonary risks for the transhiatal
      approach, while patients with advanced middle-third tumour were selected for the
      transthoracic approach. The overall leakage rate was 4%, and was the same for
      anastomosis made by the hand-sewn method, using a single layer continuous
      absorbable monofilament suture, and anastomosis made with circular stapler. The
      leakage rate was the same irrespective of whether the anastomosis was made in the
      neck or in the chest. However, stapled anastomosis has the disadvantage of a
      higher risk of fibrotic stricture formation. The 30-day and hospital mortality
      for the 785 patients was 5% and 14%, respectively. An improvement in the hospital
      mortality was observed over the 12-year period, with a 16% incidence for the
      first six years, and 11% for the subsequent six years (P = 0.03). The five-year
      survival after curative and palliative resection was 35% and 6%, respectively,
      and was 18% overall.

PMID- 7574379
TI  - Carcinoma of the gastric cardia.
AB  - The general term "carcinoma of the gastric cardia" includes three different types
      of adenocarcinomas. Carcinoma of the distal oesophagus (Type I), true carcinoma
      of the cardia (Type II) and subcardial gastric carcinoma (Type III). The
      preoperative classification of these carcinomas of the gastro-oesophageal
      junction is primarily based on radiologic and endoscopic examination. The most
      accurate method for preoperative staging is endosonography; if this shows that
      complete tumour resection is not possible, preoperative chemotherapy for
      downstaging of the tumour is suggested. As the serosal cover on the back wall of
      the cardia and the gastric fundus is lacking, the Union Internationale Contre le
      Cancer (UICC) pT2 classification includes wall penetrating tumours which would be
      equivalent to pT3 in other parts of the stomach. For prognostic reasons these
      advanced carcinomas should be classified as pT2b in contradistinction to tumours
      limited to the muscularis propria (pT2a). The results of surgical resection of
      445 carcinomas of the gastric cardia are presented (Type I 38%, Type II 28%, Type
      III 34%). The overall 30-day and 90-day mortality rates were 4.9% and 10.4%,
      respectively. Long term survival after resection of carcinoma of the gastric
      cardia was mainly associated with complete tumour removal, limited wall
      penetration and absence of lymph node metastases. Patients with Type I cancers
      showed a tendency for a better outcome compared to Type II and III because of a
      higher percentage of early cancers and a higher rate of complete tumour
      resection.

PMID- 7574380
TI  - Lymph node dissection for thoracic esophageal carcinoma. Two- and 3-field lymph
      node dissection.
AB  - Patients' records were analyzed to evaluate the effect of lymph node dissection
      on the survival of patients with thoracic esophageal carcinoma. Patients who
      underwent incomplete resection of the tumor were excluded from this study. A
      conventional lower mediastinal and abdominal lymph node dissection (conventional
      2-field dissection) had been performed in 410 patients. A complete dissection of
      the upper mediastinal nodes was performed in addition in 121 patients (extended 2
      field dissection). Sixty-four patients underwent a further dissection of the
      cervical periesophageal lymph nodes through the thoracic cavity (super-extended 2
      field dissection). A cervical, mediastinal, and abdominal lymph node dissection
      was carried out in another 100 patients (3-field dissection). Background factors
      in the latter three groups were similar. Mean numbers of dissected lymph nodes in
      extended 2-field, super extended 2-field, and 3-field dissections were 32, 57,
      and 77, respectively. Operative mortality rates were 11%, 9%, and 3%,
      respectively. The five-year survival rates for patients who underwent extended 2
      field or 3-field dissection were 43% and 61%; the difference was statistically
      significant (P = 0.000113). The four-year survival rate for super-extended 2
      field dissection was 53%. Among those patients who underwent 3-field dissection,
      58 (58%) had histologically positive lymph nodes. Their five-year survival rate
      was 47%. The patients' survival has been improved by increasing the field of
      lymph node dissection without deterioration of operative mortality.

PMID- 7574381
TI  - Therapeutic options for cancer of the hypopharynx and cervical oesophagus.
AB  - Between 1980 and 1990, 291 patients with a cancer in the cervical area of the
      oesophagus were admitted to our Department: in 187 the cancer was located mainly
      in the cervical region, 76 in the hypopharynx and 28 had a tumour that had spread
      to the cervical oesophageal region following laryngectomy. Most tumours of the
      hypopharynx involved the cervical oesophagus when it was often difficult to
      define the site of origin. 153 patients (53%) underwent surgical resection which
      included a modified neck dissection followed by different kinds of
      reconstruction. 96 patients underwent pharyngogastric anastomosis. Twenty
      anastomotic leaks (23%) were recorded including both those clinically evident and
      asymptomatic ones detected radiologically. Moreover, segmental proximal necrosis
      was seen in ten patients. Hospital mortality rate after pharyngogastric
      anastomosis was 14.7% (14/95). Colon interposition was used in 11 patients. Two
      anastomotic leaks and two partial necroses were observed. Hospital mortality was
      18% (2/11). Eighteen patients underwent laryngopharyngectomy and cervical
      oesophagectomy with reconstruction performed by means of revascularized jejunal
      loop. One anastomotic leak was observed and hospital mortality was nil in these
      cases. Twenty-four patients underwent total oesophagectomy with larynx
      preservation when the cancer was located at least 2 cm below the upper
      oesophageal sphincter. Five anastomotic leaks and two partial necroses occurred
      and hospital mortality was 8.3% (2/24) in these patients. The remaining five
      patients operated on underwent miscellaneous surgical procedures with one
      postoperative death. Overall survival for resections considered curative was
      21%:37% for hypopharyngeal and 18% for cervical cancers respectively, while it
      was nil at three years after palliative resection and total oesophagectomy with
      larynx preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574382
TI  - Role of videoassisted surgery in the treatment of oesophageal cancer.
AB  - The author analyses the pros and cons of the so-called minimally invasive
      oesophageal surgery for cancer, in the light of his own experience and the major
      studies reported in the surgical literature and recent congresses. He concludes
      that, although radical oesophagectomies are feasible on selected patients, a
      major oesophageal operation carried out through small parietal incisions remains
      an invasive procedure owing to the magnitude of the internal dissection and the
      relatively poor general condition of the patients. In contradistinction, both
      exploratory thoracoscopy and laparoscopy are very attractive alternatives to the
      classic tools of diagnosis and staging.

PMID- 7574383
TI  - Multimodal treatment of oesophageal carcinoma.
AB  - Surgery, radiotherapy, and chemotherapy are the main treatment arms for
      oesophageal carcinoma, and surgical resection is considered as the first choice
      for curatively resectable tumours. But the prognosis is poor even in the patients
      who received curative resection, and adjuvant therapy has therefore been
      investigated, now for over thirty years. Preoperative radiotherapy or
      chemotherapy have a good effect on the tumour, but prognosis is not improved over
      surgery alone. Postoperative radiotherapy results in slightly higher survival
      rates than preoperative radiotherapy. Preoperative chemoradiotherapy has a
      greater effect on the tumour, but operative mortality is increased, and long time
      survivors consist of only those who have no cancer cells in the resected
      specimen. Patients with residual tumour do not survive for a long time. On the
      other hand, Leichman reported higher survival rates in patients with
      chemoradiotherapy who did not have surgery compared with those who had received
      chemoradiotherapy followed by surgery. Surgery thus did not have additive effects
      in this treatment modality. It is important therefore that prospective,
      randomized trials comparing chemoradiotherapy with or without surgery are carried
      out in the near future. The present consensus is that surgical resection is
      recommended for Stage I, II and parts of Stage III carcinomas, and adjuvant
      therapy is necessary for those with positive lymph node metastases and/or a
      positive surgical margin.

PMID- 7574384
TI  - Special considerations of oesophageal surgery. Strategies of treatment for
      oesophageal perforations.

PMID- 7574385
TI  - Oropharyngeal dysphagia and disorders of the upper esopharyngeal sphincter.
AB  - Upper Esophageal Sphincter (UES) dysfunction is difficult to evaluate and
      quantitate. Results of treatment are influenced by the etiology and extent of
      damage responsible for the dysfunction. Classification and approach to the
      patient with oropharyngeal dysphagia are described. Results of surgical therapy
      for this functional dysphagia are discussed.

PMID- 7574386
TI  - Oesophageal atresia--need for life-long follow-up?

PMID- 7574387
TI  - Oesophageal substitution.

PMID- 7574388
TI  - [Temporal muscle flap in cranio-facial reconstructive surgery. Apropos of 32
      cases].
AB  - The temporalis muscle flap is used in craniofacial reconstructive surgery to
      repair defects, to restore facial contours and to cover bone grafts. These
      possibilities of reconstruction are analysed in the light of 32 cases. After
      reviewing the anatomy and the surgical technique, this series is presented as a
      function of the various types of defect: cranio-orbital (9 cases), defects of the
      malar area (6 cases), maxillary defects (7 cases), mandibular defects (7 cases),
      malar and parotid soft tissues defects (2 cases), mastoid defects (1 case). This
      study indicates that the temporalis flap possesses several advantages: great
      vascular reliability, associated with simplicity of flap raising and an easily
      available tissue volume. The arc of rotation constitutes the limiting factor.
      Romberg's syndrome does not constitute an ideal indication of choice, as the
      muscle may be atrophied. Similarly, when the defect requires thin cover, it would
      be wiser to use a thinner flap, such as fascia temporalis superficialis. Donor
      site sequelae are negligible. Limitation of mouth opening (3 cases) and frontal
      paralysis (2 cases) are usually transient. The field of application of this flap
      can be extended by continuing the flap as far as the pericranium or calvarium,
      allowing complex reconstructions.

PMID- 7574389
TI  - [Reconstruction of chronic facial paralysis by free gracilis muscle transfer.
      Apropos of 59 cases].
AB  - Surgical repair of facial paralysis is designed to restore automatic and uniform
      facial expression. The authors report their experience of 64 patients with
      longstanding facial paralysis treated by revascularized and reinnervated gracilis
      muscle transfer. Reinnervation of the gracilis muscle was obtained by anastomosis
      of its motor nerve to the facial nerve on the healthy side following preliminary
      transfacial nerve graft. 59 patients were followed for 1 to 8 years; the mean
      duration of facial paralysis was 14 years in this series. The authors modified
      the gracilis muscle harvesting technique by decreasing the muscle mass to a
      minimum. Two complications were observed: one severe infection leading to
      thrombosis of the anastomosed vessels and one intraoperative technical difficulty
      concerning the nerve anastomosis. The results were considered to be good in 72%
      of cases and excellent in 5% of cases in terms of facial expression. However,
      good results were not obtained in muscle transfer for palpebral paralysis, in
      which the authors prefer to make the eyelid heavier by inserting a gold weight
      implant after modifying this technique to lower the rejection rate.

PMID- 7574390
TI  - [Lateral trapezius flap in cervico-facial surgery. Apropos of 89 cases].
AB  - Described since 1976, the lateral trapezius flap is not very used in cervico
      facial reconstructive surgery because of its dissection which is considered as
      difficult and because of the variability of its vascular pedicle. This latter
      problem can be removed by the systematic use of preoperative arteriography. We
      present our retrospective experience of 89 flaps (70 cases of tumors and 19 cases
      of balistic pathology. We can conclude that the lateral trapezius flap owns
      specific indications: cutaneous and mucous defects of lips and cheeks, defects of
      pharyngeal area, defects of floor of the mouth considering of its thin thickness,
      mandibular defects where it takes place between reconstructive plates and
      revascularized bone transplants especially for the symphysis area.

PMID- 7574391
TI  - [Ulnar parametacarpal flap. Anatomical study and clinical application].
AB  - The ulnar border of the hand provides a new skin flap which is very useful in the
      reconstruction of defects of the palm of the hand and ulnar fingers. An
      anatomical study of the dorsal carpal branch of the ulnar artery and its various
      branches has led us to propose the ulnar parametacarpal flap either as a pedicle
      or free microsurgical transfer. The territory of the dorsal carpal branch of the
      ulnar artery allows harvesting of a simple sensitive skin flap or a composite
      flap comprising a bone or tendon island flap. Description of the distal
      communicating vessels with the ulnar collateral artery of the little finger
      extends the territory of the ulnar parametacarpal flap; based on a retrograde
      blood supply, it can reach the dorsal and palmar surfaces of the ulnar fingers.
      The authors present several clinical applications and define the place of this
      new flap among the various treatment options for the hand.

PMID- 7574392
TI  - [Posterolateral sural fasciocutaneous island flap with proximal aponeurotic
      pedicle. Anatomical study and use for cutaneous cover of the knee. Apropos of 9
      clinical cases].
AB  - The authors propose an elaborate variant of the classical saphenous or lateral
      leg fascio-cutaneous flap with a proximal pedicle for the cover of post-traumatic
      skin defects of the knee. The original feature of this flap resides in the purely
      aponeurotic or adipo-fascial pedicle which increases the arc of rotation, while
      minimizing cutaneous sequelae of the donor site. Twenty four injected cadaveric
      dissections were used to define the neurovascular content of the lateral sural
      fascia: the lateral and medial superficial sural arteries and their territory of
      perfusion, accompanying veins and the short saphenous vein, as well as the
      lateral and medial sural cutaneous nerves. The technique of harvesting of the
      island flap is described. Nine patients were operated between 1991 and 1994, with
      an uncomplicated postoperative course in terms of flap vitality and donor site.
      The skin cover of the knee was considered to be of excellent quality, stable and
      sensitive, with a follow-up ranging from 6 months to 3 years four months.

PMID- 7574393
TI  - [Mid-plantar pedicle skin flap. Apropos of 5 clinical cases].
AB  - The blood supply to the non-weight bearing midsole area is not derived
      exclusively from the medial plantar artery. This allows elevation of a subfascial
      mid-plantar cutaneous flap for the reconstruction of the heel. The technique of
      elevation of the flap is described. This plantar flap can be designed to include
      sensation without the need for deep dissection. Five clinical cases are
      discussed. This flap is useful for medium-sized chronic ulcerations of the heel.

PMID- 7574394
TI  - [Eyelid repair using the Hubner technique].
AB  - Many methods have been proposed for the reconstruction of full thickness defects
      of the eyelid are numerous, but all are imperfect. The texture, colour, and
      functional role of the eyelid require the use of a ciliated composite transplant.
      Among the various techniques described, Hubner's transplants, free transfers of a
      segment composed of connective tissue of the tarsus and the ciliary margin of the
      contralateral eyelid, covered by a palpebral flap, can be used to reconstruct a
      hemi-eyelid, or even two-thirds of the eyelid with good aesthetic and functional
      results.

PMID- 7574395
TI  - [Mento-sternal fistulae. Review of the literature. Apropos of 4 cases].
AB  - Mentosternal fistula is a very rare entity. 70 cases had been reported in the
      French literature up until 1984. Mentosternal fistula is very different from cyst
      and fistula of the thyroglossal duct. There is no consensus concerning both
      pathologically and embryologically, the ethiopathogenesis of mentosternal
      fistula, but the most widely accepted embryological theory seems to be inclusion
      of ecto or endodemic material at the time of fusion of the branchial tissues in
      the cervical midline. Clinical features, in the complete form, are very typical
      and must be distinguished from thyroglossal duct anomalies. No thyroid
      exploration is required before the surgical procedure which must be simple and
      complete.

PMID- 7574396
TI  - [Subperiosteal face lift with endoscopic assistance. Role of endoscopy analyzed
      apropos of 26 cases].
AB  - We present a brief report about the history of the subperiosteal face lift and
      its evaluation. The advantages of the procedures are analyzed together with the
      application of the endoscopic approach which avoids the coronal incision. The
      technical bases, the dissection performed and the method for internal suspension
      of the deep soft tissues are described. The endoscopic approach provides
      excellent results, with less surgical aggression, less swelling and faster
      recovery.

PMID- 7574397
TI  - [The omentum presented by our ancestors...].

PMID- 7574398
TI  - [The greater omentum. Its role in reconstructive plastic surgery].
AB  - The greater omentum, an original visceral flap, offers great possibilities of
      repair of complex defects. First proposed in the 1960s following the work by
      Kiricuta, rejuvenated following a better understanding of its physiology as a
      result of recent research, the value of the omentum resides in its specific
      properties of defence, detersion, and revascularization. During laparotomy, the
      only way of determining the extent of this organ (an average of 400 cm2) and
      defining its blood supply, the surgeon may decide to perform a flap on the left
      or right gastro-omental pedicle. The right pedicle is dominant with an artery and
      a vein which have a mean calibre of 2 millimeters. After colo-omental detachment
      and release of the greater curvature, the omentum pedicle flap reaches the entire
      anterior surface of the trunk, the proximal part of the limbs, and the base of
      the neck. It can be used as a free graft, or may be revascularised by
      microsurgery. It can be transferred to any site, especially to the proximal part
      of the lower limb. An immediate or secondary split-skin graft ensures cover of
      the organ. The indications for omentoplasty are eclectic, but restricted in
      relation to the initial proposals: it should no longer be used to reconstruct a
      relief nor to dry up bony suppuration, or to drain lymphoedema. The situations in
      which omentum still remains indicated, or even irreplaceable, are those in which
      a free or local flap is impossible, insufficient, or uncertain: poorly defined,
      deep, torpid, infected defects and cases of radiation necrosis, pharyngostomy,
      thoracic empyema (especially those maintained by a bronchial fistula). In cancers
      of the oropharynx, the addition of a conjoint potion of the stomach allows
      reconstruction of gastrointestinal continuity. In traumatology, an omental free
      flap can save a leg or a foot, with bony disruption and major soft tissue
      destruction. The only limitation to the use of the greater omentum is the
      laparotomy, which cannot always be performed in patients with respiratory failure
      or following multiple abdominal operations. Apart from this reservation, the
      omentum remains an "extreme" flap for "extreme" situations.

PMID- 7574399
TI  - [Siliconomas].

PMID- 7574400
TI  - [Eyelid burns. An 11-year retrospective evaluation].
AB  - This retrospective study has concerned 1115 adults burns patients hospitalized
      between January 1, 1984 and December 31, 1994 in the CHU Trousseau Burns Centre
      in Tours. 448 patients who suffered from facial burns were treated in the centre.
      The rate of facial burns and association with hand burns were observed as usually
      described, as well as the severity of chemical injuries and prolonged exposure to
      a heat source. 87 patients underwent grafting of the face and 33 of these
      patients, were grafted on the eyelids with or without grafts on other areas of
      the face. Grafting procedures on the eyelids were performed an average of 23.4
      days after the injury although the medical staff of the centre had always
      emphasized the importance of early excision followed by grafting during the same
      procedure. However, the data showed that grafting was performed significantly
      earlier when good results (no functional disorders, no chronic conjunctivitis, no
      ectropion, good mobility) were obtained: 21.6 days versus 34.3, p < 0.05. The
      causes of the surgical delays observed and the various surgical methods are
      discussed.

PMID- 7574401
TI  - [Reconstruction of the nose in deep extensive facial burns].
AB  - The nose is in the medial portion of the face and is frequently injured in trauma
      of this area. Due to its situation its structure and shape, and its essential
      function, this organ is particularly exposed in the case of facial burns. These
      injuries, are usually associated with larger injuries, and frequently with
      systemic problems, such as respiratory problems. The authors describe nasal burns
      in the larger context of facial burns, and summarize recent data on this topic.
      They then recall the fascinating story of rhinopoiesis through the ages. The
      third part is devoted to their personal approach to reconstruction of the nose in
      severe panfacial burns, using a forehead flap with one or several tissue
      expanders.

PMID- 7574402
TI  - [Secondary reconstruction of the external ear destroyed by burns. Indications and
      techniques. Apropos of 30 clinical cases].
AB  - Reconstruction of an ear destroyed by burns raises several difficulties related
      to the presence of associated lesions. The essential element determining the
      indication for reconstruction is the possibility to cover a three dimensional
      cartilaginous graft with skin. Depending on the local condition of the skin,
      retroauricular skin, a temporal fascia flap or preliminary expansion may be
      indicated. Reconstruction should be performed when the chances of obtaining a
      good result are sufficient in a motivated patient. If these conditions are not
      satisfied, prosthesis should be proposed.

PMID- 7574403
TI  - [Ear prostheses in burns of the external ear. Technical notes].
AB  - Ear reconstruction is best performed with autologous tissue. However, there are
      selected cases in which a prosthesis may be preferred. Some patients are
      unwilling to undertake multiple surgical procedures, others do not accept the
      chest wall scar. More importantly, in severe post burn cases, the scars in the
      periauricular region can truly compromise the outcome of an autologous
      reconstruction. In such cases, the authors perform a prosthetic reconstruction
      which is anchored to the cranial bone by means of osteointegrated titanium
      screws. The method described here has been modified compared to the original
      Branemark system. A new microscrew design allows the implants to be inserted in a
      single surgical procedure. A magnetic anchoring system avoids cumbersome external
      rods, and the overall size of the masses emerging from the skin is significantly
      reduced. These improvements increase patient comfort and compliance.

PMID- 7574404
TI  - [Secondary surgical restoration of contours and volumes of facial burns].
AB  - Recent progress in plastic surgery techniques have clearly contributed to the
      improvement of the aesthetic prognosis of facial burns. However, although current
      excision-graft techniques achieve good quality skin, often in sufficient
      quantity, these grafts give the face a fixed, inexpressive, flat mask appearance,
      du to the inevitable phenomena of scar retraction. To palliate this unsightly
      appearance of the grafted face, the authors restore the principal facial relief
      (eyebrows, cheekbones, nostrils, philtrum, lips, chin) by using, depending on the
      particular case, subperiosteal parietal bone grafts, or flaps of scar tissue
      grafted immediately or secondarily. The authors report their experience and
      describe the techniques, indications, as well as the advantages and disadvantages
      of these various procedures.

PMID- 7574405
TI  - [Previously expanded full-thickness skin grafts. Technical principles.
      Indications in the repair of sequelae of burns. Apropos of 22 cases].
AB  - Burns raise difficult repair problems. Previously expanded full-thickness skin
      grafts represent a good solution in many situations. Based on their experience of
      22 cases, the authors present a review of the various indications for this
      technique.

PMID- 7574406
TI  - [Role of autografts of cultured epidermis in the treatment of deep burns of the
      face. Preliminary results].
AB  - Deep burns of the face raise the problem of skin cover after surgical detersion
      to limit the  serious functional and aesthetic sequelae which they can induce.
      Autologous cultured epidermal grafts currently occupy an important place in the
      surgical treatment of the early phases of facial burns. The authors present their
      preliminary results of the use of this graft technique in patients with burns of
      more than 60% of the body surface, including the face. The surgical protocol is
      described, consisting of surgical detersion with benzoic acid, grafting and
      specific dressings. Three patients treated by this technique are then presented
      before concluding on the very interesting prospects of autologous culture
      epidermal grafts on a fibrin substrate. A clinical case of facial burns treated
      by this new type of graft is presented to conclude the discussion.

PMID- 7574407
TI  - [Device of the burnt face. Role of compression and splints].
AB  - The face is one of the areas of the body most frequently affected by burns.
      Pressure therapy maintains facial scars until maturation is achieved to present
      hypertrophic scars or contractures. Elastic pressure garments are usually used,
      but they do not provide adequate pressure on areas such as naso-labial folds or
      labio-chin folds. Silicone splints are therefore added under this elastic face
      mask. A rigid transparent face mask or silicone face mask allows better
      management of facial scars. A positive plastic mold is obtained from a negative
      alginate mold of the patient's face. A high temperature plastic is heated and
      stretched on to the positive mold. The mask is worn continuously excepted when
      bathing eating and rehabilitation. Follow up is necessary to prevent
      complications and to revise the mask as the scars change. Nostril and oral
      commissures are treated with inserts which maintain adequate size or corrected
      contractures. Satisfactory results can be obtained with cooperative patients.

PMID- 7574408
TI  - [Open forum: plastic surgery and burns].

PMID- 7574409
TI  - [Treatment of retractions of the neck after burns ... in the last century].

PMID- 7574410
TI  - The drug problem: therapeutic effectiveness, unwanted reactions, and cost.

PMID- 7574411
TI  - Effect of growth hormone on bone marrow grafts in fracture healing--an
      experimental study in rabbits.
AB  - The lack of effectiveness of growth hormone in stimulating the healing of fresh
      fractures has been attributed to the presence of insufficient precursor
      osteogenic cells at the fracture site for the growth hormone to exert its
      influence. We tested the effect of growth hormone on healing in a rabbit non
      union model after injection of autogenous marrow cells into the fracture gap. Two
      millilitres of bone marrow were injected percutaneously into 1 cm diaphyseal
      defects of rabbit radii. The test group was given subcutaneous human recombinant
      growth hormone at 0.3 IU/kg/day in divided doses for 2 weeks, while the control
      group received subcutaneous saline injections. Biomechanical, radiological and
      callus calcium content assessments were carried out at 4 and 7 weeks. There was
      significantly increased tensile strength and callus calcium concentration in the
      group given growth hormone both at 4 and 7 weeks but there was no significant
      difference in stiffness or in callus volume in the 2 groups. These data suggest
      that growth hormone can enhance the osteogenic potential of bone marrow as a
      graft in the treatment of fracture non-union.

PMID- 7574412
TI  - Comparison study of DNA content of primary and metastatic lymph node lesions of
      colorectal cancer.
AB  - Abnormal DNA content or aneuploidy in cells usually indicates malignancy. In
      colorectal cancer aneuploidy has been shown to confer a poorer prognosis
      suggesting that aneuploid cancers are more aggressive. The mechanisms involved in
      the aggressive behaviour of an aneuploid tumour are still unknown. The aim of
      this study was to compare the patterns of aneuploidy of colorectal cancers and
      that of their corresponding lymph node metastases and to relate them to clinical
      outcomes. One hundred and one patients were studied, 81 (Dukes C) with lymph node
      metastasis only and 20 (Dukes D) with obvious distant metastasis as well. Forty
      six (46.5%) of the tumours and an equal number of the lymph nodes were found to
      be aneuploid. Twenty-eight (60.9%) of the aneuploid tumours showed aneuploid
      metastasis and 18 (39.1%) showed diploid metastasis. Similarly, 37 (67.3%) of the
      diploid tumours showed diploid metastasis whereas 18 (32.7%) showed aneuploid
      metastasis. Local recurrence and distant metastasis were compared among the
      aneuploid and diploid primary tumours. Although there was no statistically
      significant difference, distant metastasis was more common in aneuploid tumour.
      Ploidy of the lymph node was not related to local recurrence or distant
      metastasis. We conclude that DNA ploidy by itself does not determine the
      metastatic potential of the tumour cell and that in about 50% of the tumours, the
      lymph node metastasis consists of clones of cells different from the primary
      tumours. We also conclude that the clinical outcome of the disease in terms of
      recurrence and metastasis cannot be predicted by the ploidy of the lymph node
      metastatic lesions.

PMID- 7574413
TI  - Infection in diabetic patients with ankle fractures.
AB  - Between January 1992 to June 1993, 93 ankle fractures underwent surgical
      treatment, of which, 10 patients were diabetic and 83 were non-diabetic.
      Infection occurred in 5 patients and all belonged to the diabetic group. The
      average follow-up period of the infected cases was 16.2 months. Wound infection
      occurred in 4 patients treated with open reduction and internal fixation. An
      infected pressure sore developed in the other patient treated initially in a
      below-knee cast for which arthrodesis of the ankle was performed. Infection was
      resistant to treatment in 2 patients and they ended up with below-knee
      amputation. Infection resolved in 3 patients with treatment. Of these, 1
      developed neuropathic ankle joint and the other 2 achieved fracture union.

PMID- 7574414
TI  - Pulmonary thromboembolism is not uncommon--results and implications of a five
      year study of 116 necropsies.
AB  - A retrospective study of 116 cases of fatal pulmonary thromboembolism, drawn from
      a total of 11,044 Coroner's autopsies, conducted over a 5-year period, yielded a
      necropsy prevalence of 1.05%, with an annual incidence varying between 0.78%
      1.32%. There was a statistically significant peak monthly incidence of 1.89% in
      September (P < 0.03), as well as significantly higher rates between April to
      September as a whole, compared to the rest of the year (P < 0.03). There was a
      marked preponderance of females (male:female ratio = 0.59) and 48.3% of the
      subjects were > or = 60 years of age, with a distinct peak (23.3%) in the 8th
      decade. The prevalence of the common predisposing factors were as follows:
      surgery 41.4%, trauma 30.2%, sepsis 22.4%, obesity 18.1%, malignancy 10.3% and
      pregnancy 4.3%. The peak time of death following trauma and/or immobilization was
      one week. Apparently, a total of 54 subjects (46.6%) were ambulant prior to
      death, while 29 (25%) did not have any of the common risk factors studied. The
      prevalence of cigarette smoking and oral contraception could not be ascertained
      due to inadequate clinical documentation, even among medical inpatients. The
      majority of deaths (85.3%) occurred in hospitals, of which 44.8% were surgical
      patients. Pulmonary thromboembolism was apparently not suspected in 77.1% of the
      105 patients who died whilst under the care of qualified medical practitioners,
      there being no significant difference between medical and surgical inpatients. In
      these cases, death was most often attributed to acute myocardial infarction or
      ischaemic heart disease. The study also showed a high prevalence of underlying
      chronic obstructive airways disease (37.1%) and of moderate to severe coronary
      atheroma (37.9%). The clinico-pathological and medico-legal implications of these
      findings are discussed.

PMID- 7574415
TI  - Ureteric colic: value of initial investigations and the outcome.
AB  - During a one-year period (from April 1992 to April 1993), 294 patients with the
      complaint of ureteric colic seen at the Emergency Department of Tan Tock Seng
      Hospital were investigated with a plain X-ray of the kidney, ureter and bladder
      (KUB), urinary analysis (urine FEME) and subsequently intravenous urogram (IVU)
      at the outpatient clinic. The results showed that majority (73%) of the patients
      were male. Sixty percent of the cohort were in the age group 30-50 years. After
      evaluation, it was found that only 114 (39%) of the patients with ureteric colic
      had abnormal IVU. Among these patients, 99 were diagnosed to have calculus
      disease, 12 with urothelial tumours, 1 with renal cyst and 2 had no pathology
      detected. Nevertheless most (72%) of the patients did not require intervention.
      In addition, it was noted that if the KUB or urine FEME was positive, the chances
      that a urological pathology was present were 72% and 91% respectively. However,
      if both of them were negative, the chance that a pathology would not be present
      was 93%. This suggests that patient selection is very essential to avoid
      unnecessary investigations.

PMID- 7574416
TI  - Oropharyngeal reconstruction after ablative surgery of the head and neck-
      experience of 93 cases.
AB  - The surgical defect after radical resection in the head and neck region is
      extensive and often involves skin, oral mucosa and bone. Primary reconstruction
      allows for rapid restoration of function and rehabilitation of the patient. We
      report a series of 93 patients with oropharyngeal reconstruction after ablative
      surgery in the head and neck. For reconstruction, there were 41 pedicled
      myocutaneous flaps, 18 random flaps and 7 vascularised free flaps. There were 3
      partial and 1 complete flap failures together with 5 persistent fistulas. The
      factors considered in the choice of reconstruction and our philosophy in this
      regard are discussed.

PMID- 7574417
TI  - A descriptive profile and the immune status of some hospitalised patients with
      measles.
AB  - The incidence of measles in Singapore has declined with the introduction of
      measles vaccination in 1976. However, a progressive increase in notified measles
      cases has occurred since 1990. To characterise the current profile of
      hospitalised patients with measles, particularly their measles immunity status,
      we analysed 46 cases over a period of 3 months. The majority (69.6%) were school
      going children (aged 5-19 years). Of the 25 patients (54.3%) classified as
      preventable by immunisation according to the current strategy, 68% were school
      age persons. Five previously vaccinated patients had measles enzyme immunoassay
      immunoglobulin M and immunoglobulin G antibodies present. The occurrence of
      preventable cases among school-age children indicates that the implementation of
      the current immunisation programme should be improved.

PMID- 7574418
TI  - Anorectal physiological parameters in chronic constipation of unknown aetiology
      (primary) and of cerebrovascular accidents--a preliminary report.
AB  - Chronic constipation may be secondary to dietary, metabolic or neurological
      causes such as cerebrovascular accidents (CVA). In certain patients, the cause is
      unknown (primary idiopathic constipation [PIC]). This study compared the
      anorectal physiological parameters of 15 PIC patients (all females; median age
      40, range 32-48 years) with 7 CVA patients (M:F = 6:1; median age 58, range 51-67
      years), to observe the influence of cerebral factors on the anorectal physiology
      of constipation. Twenty-five normal subjects (M:F = 13:12; median age 47, range
      43-50 years) acted as controls. Transit marker studies showed decreased passage
      in both groups, but 9 of the PIC patients had a diffuse pattern (slow transit
      constipation [STC]) and 6 had a pelvic outlet obstruction pattern (PO). The CVA
      patients had a diffuse pattern of delayed transit. Rectal sensation was
      significantly impaired in STC (P < 0.05) but not in PO or CVA. Electromyographic
      evidence of paradoxical puborectalis contractions was significantly more common
      in PO only (P < 0.05). Therefore, CVA patients had a different anorectal
      physiological pattern of constipation from PIC patients.

PMID- 7574419
TI  - Surgical treatment of symptomatic accessory navicular.
AB  - The accessory navicular is a known cause of foot pain. When symptomatic and
      conservative measures have failed, surgical intervention may be required. Simple
      excision of the ossicle or the Kidner procedure with transplantation of tibialis
      posterior tendon to the undersurface of the navicular bone may be done. Eighteen
      patients with symptomatic accessory navicular were reviewed at the Singapore
      General Hospital, Department of Orthopaedic Surgery 'O' Unit. All 18 patients had
      foot pain and restriction of activities. Thirteen noticed a prominence on the
      medial side of the affected foot and 7 had difficulty with shoe fitting. Nine
      underwent simple excision of the ossicle while the other 9 had the Kidner
      procedure done. The average follow-up period was 3.1 years. Both the simple
      excision and the Kidner procedure were equally successful in relieving symptoms
      in 15 out of the 18 cases. The Kidner procedure did not confer any particular
      advantage over simple excision.

PMID- 7574420
TI  - Mortality analyses of the 1990 Singapore population: I. General life tables.
AB  - General life tables for the 1990 Singapore resident population are given in this
      paper. Analyses were carried out separately for males and females for all ethnic
      groups as well as for Chinese, Malays and Indians. Average fractions of the last
      age interval lived were used to give a more precise derivation of the life table
      death rates from their corresponding age-specific death rates. The results show
      that in 1990, Singapore males had achieved a life expectancy at birth of 73.7
      years while the females had attained a level of 78.6 years. These levels were
      comparable to those of many developed countries. Other interesting features
      include higher differentials in the life expectancies between sexes among the
      Chinese and the Indians taking over the Malays for second placing in terms of
      life expectancy at birth for both sexes. As a result, the Indians registered a
      12% gain in life expectancy at birth for males for the decade 1980 to 1990,
      compared to only 7.1% for Chinese and 4.4% for Malays as well as nearly 10% for
      females compared to only 6.2% for Chinese and 6.3% for Malays. A subsequent paper
      will highlight the results of multiple-decrement life table analyses which will
      summarise the mortality of the 1990 Singapore resident population for various
      component causes of death rather than for all causes combined.

PMID- 7574421
TI  - Association of activated proto-oncogenes ras and myc in colorectal carcinomas.
AB  - We have examined 60 colorectal carcinomas for activation of two proto-oncogenes,
      c-myc and c-Ki-ras. Over-expression of c-myc mRNA as determined by Northern
      analysis was found in 58% of cases (35/60). Activation of the c-Ki-ras gene by
      point mutations in codons 12 or 13 as determined by mismatch specific
      oligonucleotide hybridisation was found in 35% (21/60) of cases. There was a
      statistically significant association between activation of c-Ki-ras and over
      expression of c-myc (P = 0.03), with 76% of tumours with an activated c-Ki-ras
      proto-oncogene showing over-expression of c-myc. The association was significant
      in left-sided colorectal tumours (P = 0.03) but not right-sided (P = 0.5).
      However, whereas only 59% of left side tumours showed at least one of the two
      changes (ras activation only, or myc activation only or both), 93% of right side
      tumours showed at least one of the changes (P = 0.01). Twenty-two percent of left
      side tumours showed both changes compared with 35% of right side tumours,
      although this result did not achieve significance (P = 0.2). These results
      suggest that in left-sided colorectal tumours ras and myc cooperate, as
      established in vitro, to produce neoplastic transformation while different
      pathway(s) are involved in right-sided tumours.

PMID- 7574423
TI  - Ventilatory function measured with the Micro Spirometer: performance evaluation
      and reference values.
AB  - The performance of the Micro Spirometer was compared with that of the Vitalograph
      by assessing the extent of agreement between the instruments and the
      repeatability of measurements with each instrument. The Micro Spirometer tended
      to give lower readings of forced expiratory volume in one second (FEV1), forced
      vital capacity (FVC) and peak expiratory flow rate (PEFR) than the Vitalograph,
      with wide limits of agreement. The values of these ventilatory functions measured
      with the Micro Spirometer were, therefore, not directly comparable with those
      obtained from the Vitalograph, and it is also not satisfactory to predict
      readings on the Micro Spirometer from those made on the Vitalograph. In the
      management of asthma patients, the PEFR would still be preferably measured with
      the mini Wright peak flow, given its low cost and established reliability
      compared with the standard Wright peak flow meter. The Micro Spiromoter has the
      practical advantages of portability, ease of operation and relative cheapness for
      the baseline and long-term assessment of FEV1 and FVC in ambulatory care, as well
      as in epidemiological studies. However, local users should not employ reference
      values provided by the manufacturer or those published in the literature, but
      those reported in this paper.

PMID- 7574422
TI  - Allelic loss of the p53 gene in colorectal cancer.
AB  - The loss of specific chromosomal loci in cancers is indicative that the region
      contains a tumour suppressor gene. Allelic loss of chromosome 17p has been shown
      to occur in a wide variety of cancers such as lung, breast, colon, ovary and
      brain and, until recently, the gene believed to be involved was the p53 tumour
      suppressor gene. However, more recent studies have shown that the area deleted in
      some of these tumours does not include the structural gene for p53. For this
      reason it has been proposed that a tumour suppressor gene lying distal to p53 on
      chromosome 17p is the gene deleted in these cancers. As chromosome 17p has been
      shown to be deleted in approximately 75% of colorectal cancers, we set out to
      determine whether the target gene of these deletions was the structural gene for
      p53. Allelic loss was assessed by using restriction fragment length polymorphisms
      in 52 tumours. Deletions distal to p53 on chromosome 17p were assessed using the
      probe YNZ22.1 and allelic loss of p53 was assessed using probe pR4-2, a cDNA
      probe specific for the p53 gene. Out of the 21 tumours informative for both
      probes, 3 cases showed no allelic deletion of the chromosome 17p, 2 cases showed
      allelic deletion not encompassing the p53 gene and 16 cases (89%) showed allelic
      deletion including the p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574424
TI  - Incidental cholecystectomy--an old problem reconsidered.
AB  - This paper reexamines the issues and indications for incidental cholecystectomy
      when gallstones are present during laparotomy for an unrelated condition. Seventy
      nine such patients were studied between 1988 and 1993--66 had incidental
      cholecystectomy (both elective and emergency) while asymptomatic gallstones were
      left alone in 13 patients for various reasons. There was little morbidity and no
      mortality arising directly from biliary surgery. Interestingly, four bile
      cultures from the asymptomatic gallbladders grew bacteria and this could explain
      why patients may develop severe disease postoperatively if their gallbladders
      were left alone. The added cholecystectomy resulted in an acceptable extension of
      22 to 23 minutes in the operative time without compromising the patients' safety.

PMID- 7574425
TI  - A questionnaire-based survey of patients' knowledge of psoriasis at the National
      Skin Centre.
AB  - Psoriasis is a chronic disease, which while potentially controllable, cannot be
      cured. Treatment is long term and requires continuous effort by the patient.
      Patient education is important for a chronic disease like psoriasis and this
      involves acquiring knowledge about the disease. With knowledge gained, the
      patient will be better able to cope, improve decision-making and comply with
      treatment. The aim was to determine the level of knowledge of psoriasis among
      four groups of patients attending the National Skin Centre. The study population
      consisted of 120 patients divided into four groups with 30 patients each from the
      general clinic, psoriasis clinic, private clinic and phototherapy clinic. The
      patients were asked to fill up a questionnaire. For those who were Chinese
      educated, a Mandarin translation of the questionnaire was made. The patients' age
      ranged from 13 to 83 years with a mean of 39 years. The mean duration of
      psoriasis was 9 years. Patients from the phototherapy clinic scored significantly
      higher than patients from the other clinics. There were, however, gaps in the
      knowledge of psoriasis among the various groups. No correlation was noted between
      age, sex, duration of psoriasis, number of consultations or phototherapy session
      with correct scores to the questionnaire. The most common treatment prescribed
      for the general and private clinics was a combination of topical steroids and tar
      (67% and 44% respectively). For the psoriasis clinic, the most common treatment
      prescribed was methotrexate (60%). For the phototherapy clinic, the most common
      modality used was ultraviolet B light (60%). Education is important in the
      overall treatment of psoriasis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574426
TI  - Risk factors for birth defects in Singapore: a case control study.
AB  - To explore possible risk factors for birth defects, a matched case-control study
      was carried out at Kandang Kerbau Hospital in Singapore from January 1986 to
      December 1988. Cases and controls were selected from livebirths born in that
      hospital during that period. Cases were babies who were clinically detected as
      having defects at birth and the diagnosis reconfirmed at 6 weeks post partum.
      Each case was matched to a control by maternal age, ethnic background of mother,
      the same class of maternity ward and time of delivery. Five hundred and seventy
      two matched pairs were accrued for the study. The parents of both cases and
      controls were interviewed at 6 weeks post partum. Information on the medical and
      birth history of both mother and baby was obtained from medical records. Using
      conditional logistic regression analysis to adjust for potential confounders, the
      strongest risk factors for birth defects were family history of birth defects (OR
      3.3; 95% CI 1.8-6.4) and parents having a previous abnormal baby (OR 2.4; 95% CI
      1.1-5.3). Other notable risk factors included drug history during pregnancy (OR
      1.2; 95% CI 0.8-2.0), the ingestion of traditional medicine during pregnancy (OR
      1.4; 95% CI 1.0-2.0), injuries or accidents during pregnancy (OR 2.2; 95% CI 1.5
      3.2) and maternal diabetes mellitus (OR 1.3, 95% CI 0.3-7.1). Mothers in
      professional occupations (OR 1.4, 95% CI 0.7-2.6) and those in production
      occupation (OR 1.2, 95% CI 0.9-1.7) had an increased risk for birth defects
      compared to housewives.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574427
TI  - Clinical applications of functional electrical stimulation.
AB  - Functional Electrical Stimulation (FES) allows the restoration of controlled
      muscle contractions, and hence limb function via computer control, in patients
      with irrecoverable upper motor neuron lesions. Wide experience has been recorded
      in spinal cord injured paraplegics and tetraplegics and to a lesser extent in
      cerebrovascular accident victims. The electrodes, either surface or implanted,
      stimulate muscles electrically through a stimulator activated by a control source
      which is in turn activated by the remaining functions of the user. Future
      advances in electrode technology and control and command sources activation
      systems as well as development of "close-loop" systems need to be made if wide
      patient acceptance of this modality is to be ensured.

PMID- 7574428
TI  - Comparing computed tomographic and magnetic resonance imaging visualisation of
      the pterygopalatine fossa in nasopharyngeal carcinoma.
AB  - In a prospective study comparing computed tomography (CT) and magnetic resonance
      imaging (MRI) in the staging of nasopharyngeal carcinoma (NPC), 17 (15%) patients
      were noted to have infiltration of the pterygopalatine fossa (PPF). The
      recognition of PPF abnormalities depends on the familiarity of the normal
      anatomy. CT and MRI appearances of the normal PPF in the remaining 97 (85%)
      patients were reviewed. The fossae were symmetrical and fat was seen in all MRI
      and in 95% of the CT scans. There was destruction of the pterygoid process in 10
      (9%) patients and a further 10 patients showed erosion of the maxillary sinus.
      Superior infiltration from the PPF into the inferior orbital fissure was
      demonstrated in 7 (6%) patients. Lateral spread via the pterygopalatine fissure
      into the infratemporal fossa could be seen in 10 (9%) patients. The earliest
      indication of tumour infiltration of the PPF is the replacement of the normal fat
      content. Widening of the fossa and erosion of the bony margins are late signs. As
      expected, bony abnormality is best seen on CT. However, direct visualisation of
      tumour or replacement of fat is more elegantly demonstrated on T1-weighted MRI.

PMID- 7574429
TI  - Multidrug-resistant tuberculosis.
AB  - In 1993, the World Health Organization declared tuberculosis a global emergency.
      Tuberculosis is the leading cause of death attributable to a single infectious
      pathogen. One-third of the world's population are at risk of developing the
      disease. In countries confronted with the human immunodeficiency virus (HIV)
      epidemic, the overlap of these two populations leads to a rapid acceleration of
      active tuberculosis and of the emergence of multidrug-resistant tuberculosis.
      Multidrug-resistant tuberculosis is defined as isolates resistant to both
      isoniazid and rifampicin with or without resistance to other antituberculosis
      drugs. In the United States, outbreaks of multidrug-resistant tuberculosis have
      been reported in patients with HIV infection and acquired immunodeficiency
      syndrome (AIDS) as well as HIV sero-negative patients. These reports have caused
      great concern owing to the very high case-fatality rate. The treatment outcome of
      multidrug-resistant tuberculosis is poor. The use of second-line drugs is
      frequently associated with toxicity and intolerance. Patients require admission
      to hospitals at the beginning of treatment and adjunctive resectional surgery
      should be considered when the sputum does not convert after 4 months of therapy.
      The incidence of multidrug-resistant tuberculosis among Singapore residents
      remains low. Organisms resistant to one drug occurred in 3.8% of newly diagnosed
      tuberculosis cases with positive culture and 8.7% of relapsed tuberculosis cases
      with positive cultures. Organisms resistant to two or more drugs occurred in 1.6%
      of newly diagnosed culture positive tuberculosis cases and 4.6% of relapsed cases
      where cultures were positive. This is the result of vigilant surveillance,
      effective treatment including supervised chemotherapy and close monitoring for
      non-compliance.

PMID- 7574430
TI  - Case of pulmonary alveolar proteinosis treated by sequential whole-lung lavages
      and a review of the condition.
AB  - We report our first local case of pulmonary alveolar proteinosis that required
      symptomatic therapy with whole lung lavage. This is a rare condition associated
      with the accumulation of phospholipid material in the alveoli. The presentation
      is usually insidious and the symptomatology varies from vague complaints to
      severe crippling dyspnoea. The diagnosis is often delayed and usually made after
      the exclusion of other conditions. While there is no definitive treatment apart
      from lung transplant, whole-lung lavage is a safe, repeatable procedure which
      offers the best prospect for symptomatic, physiological and radiological
      improvement in severe cases.

PMID- 7574431
TI  - A case report on bilateral avascular necrosis of the medical cuneiforms.
AB  - Avascular necrosis rarely affects the cuneiform bones. The treatment has been
      mainly conservative and histological confirmation of osteonecrosis is therefore
      not available. The authors report a case of bilateral avascular necrosis of both
      medial cuneiforms with histological confirmation. The patient was treated
      operatively with decompression of intra-osseous pressure through multiple drill
      holes. Six weeks postoperatively, the symptoms subsided and radiographs showed
      reconstitution of both medial cuneiforms.

PMID- 7574432
TI  - Exostosis presenting as solitary loose body in the ankle of two children.
AB  - Two children, aged 5 and 11 years, presented clinically with ankle pain and a
      mobile bony hard lump in the ankle. Radiological examination revealed a large
      radio-opaque shadow in relation to the talus. Intraoperatively, a loose body was
      found. It resembled a detached exostosis with cartilaginous cap and was confirmed
      histologically as an osteochondroma. In the older child, there was a remnant
      stalk attached to the lateral surface of the talus. In the younger child, the
      exostosis probably came from the talus as the osteochondroma could not originate
      from the epiphyses that form the ankle mortise.

PMID- 7574433
TI  - Radiation-induced pericardial disease: a case report.
AB  - A typical case of chronic pericardial effusion resulting in cardiac tamponade is
      presented. A pericardiocentesis was done for diagnosis and drainage, followed by
      a pleuro-pericardial window as definitive therapy. The minimal cumulative dose
      expected to produce pericardial disease is about 4000 rads, and the disease
      usually manifests within 12 months of such radiation exposure, as in this
      patient. It is concluded that for symptomatic pericardial effusions, available
      evidence justifies a subtotal pericardiectomy, a window procedure being reserved
      to tide over ill patients as in this patient. No strong evidence exists for the
      efficacy of steroid therapy; such therapy is reserved for asymptomatic mild
      effusions, which may also resolve spontaneously.

PMID- 7574434
TI  - Kimura's disease involving the median nerve: a case report.
AB  - Kimura's disease is an uncommon chronic inflammatory process of obscure origin.
      It is more common among Orientals and affects particularly the young male. Sites
      of predilection include the head and neck region, primarily the subcutaneous
      tissue and dermis. Unusual sites of occurrence that have been reported include
      the kidney, the orbit, the ear and the spermatic cord. Kimura's disease involving
      a major nerve bundle has not been described, and we report here the findings of a
      case of histologically proven Kimura's disease of the median nerve occurring in a
      21-year-old Chinese girl. Typical diagnostic histological features of Kimura's
      disease in contrast to angiolymphoid hyperplasia, and the treatment options for
      Kimura's disease are also described.

PMID- 7574435
TI  - Carbimazole-induced agranulocytosis treated with granulocyte-macrophage colony
      stimulating factor--a case report.
AB  - Drug-induced agranulocytosis is a potentially fatal complication despite advances
      in supportive care. A patient with carbimazole-induced agranulocytosis associated
      with marked depletion of granulocytic precursors in the marrow was treated with
      granulocyte-macrophage colony stimulating factor (GM-CSF) at a dose of 5
      micrograms/kg subcutaneously daily for one week. The absolute neutrophil count
      rose above 1 x 10(9)/L after one week of GM-CSF therapy. The GM-CSF probably
      expedited the recovery of the neutrophil count. Further studies are warranted to
      delineate the role of GM-CSF in the treatment of drug-induced agranulocytosis.

PMID- 7574436
TI  - Angiographic demonstration of primary aorto-enteric fistula--a case report.
AB  - Primary aorto-enteric fistula is an uncommon but lethal disease. The key to
      patient survival is early diagnosis and treatment. Angiography may be diagnostic.
      However, angiographic documentation of this condition is rare as the patients are
      usually very ill when the decision for angiography is made. A case of primary
      aorto-enteric fistula with fatal haemorrhage is described with angiographic
      documentation. This is the first angiographically demonstrated case reported
      locally.

PMID- 7574437
TI  - Paroxysmal hypertension in a C4 spinal cord injury--a case report.
AB  - Hypertension in a patient with acute spinal cord injury is commonly caused by
      autonomic dysreflexia, which is a syndrome of paroxysmal hypertension associated
      with headaches, relative bradycardia and vasomotor instability secondary to
      sympathetic overactivity. Life-threatening complications such as seizures and
      intracerebral haemorrhage are largely preventable. We report both acute and
      chronic forms of autonomic dysreflexia due to underlying urinary and faecal
      impaction in a 33-year-old female with traumatic C4 quadriplegia. She was
      successfully managed with a combination of physical and pharmacological measures
      including calcium channel and sympathetic blockers.

PMID- 7574438
TI  - Endogenous Klebsiella endophthalmitis--a case series.
AB  - Nine eyes of 7 patients with endogenous Klebsiella endophthalmitis are presented.
      Five patients were diabetic and 4 had sepsis arising from the hepatobiliary
      system, one from the urinary tract and another from the lung. The most classical
      sign of pupillary hypopyon was present in 5 eyes. Five eyes were initially
      misdiagnosed and treated as inflammatory uveitis. Five eyes finally had no light
      perception, one eye had 6/60, another had 6/36 and two eyes of one patient
      recovered 6/6 vision. The successful outcome of this patient achieving 6/6 vision
      in either eye can be partly attributed to an early diagnosis and appropriate
      management. A high index of suspicion may improve visual outcome in such cases.

PMID- 7574439
TI  - Post-traumatic differential osteoporosis of the patella.
AB  - The differential density developing after patella fractures between the proximal
      and distal poles has been attributed to avascular necrosis of the proximal
      fragment. Six cases are presented here where differential densities between the
      proximal and distal poles developed after trauma to the patella or knee. Based on
      the natural history of the condition, the rapidity of onset of the differential
      densities, osteoporosis of the whole patella later and complete resolution of the
      changes finally, we postulate that this phenomenon is due to a differential rate
      of osteoporosis of the proximal and distal parts of the patella because of the
      differences in their blood supply and not because of avascular necrosis of the
      proximal pole.

PMID- 7574440
TI  - Fifth Seah Cheng Siang Memorial Lecture. Human immunodeficiency virus and the
      respiratory system--pulmonary manifestations of acquired immunodeficiency
      syndrome.

PMID- 7574441
TI  - [Recombinant FSH. Characteristics and therapeutical values].
AB  - Pituitary glycoproteins LH and FSH control gonadal physiology. Modern techniques
      of molecular biology have allowed the synthesis of human recombinant hormones
      (rec). In particular rec-FSH is now available for clinical use. This pure
      preparation of FSH, is available in unlimited quantity. The pharmacokinetics of
      the rec-hormone is identical to its natural counterpart. The use of rec-FSH in
      hypophysectomized women has allowed the reconfirmation of the "Two-cell--Two
      gonadotropins" theory. Indeed rec-FSH induces follicular growth without rise in
      Estradiol secretion. Clinical applications of rec-FSH and LH include ovarian
      stimulation, as well as, induction of spermatogenesis in men with
      hypogonadotrophic hypogonadism. Overall, these pure gonadotropins have the
      critical advantage of purity, reproducibility and in addition they allow easy
      modulation of the FSH/LH ratio.

PMID- 7574442
TI  - [Regulation of corticotropic function in stressful situations].
AB  - ACTH secretion is mainly controlled by two hypothalamic neurohormones:
      corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both
      peptides are synthesized in the hypothalamic paraventricular nucleus (PVN) (in
      parvo-cellular neurons for CRH and in magnocellular neurons for most AVP). Under
      basal conditions, some CRH neurons coexpress AVP (CRH+/AVP+ neurons). This
      colocalisation represents a form of functional plasticity since the number of
      CRH+/AVP+ neurons increases after acute or repeated stress exposure. Experiments
      in sheep and rat (studies on the secretion of both peptides in hypophysial portal
      blood, effects of anti-CRH and anti-AVP immunisation upon ACTH secretion)
      indicate that stress-induced ACTH stimulation involves both CRH and AVP. Unlike
      CRH which participates also in the maintenance of basal ACTH and glucocorticoids
      secretion, the role of AVP appears to be limited to corticotropic response to
      stress.

PMID- 7574443
TI  - [Growth hormone receptor and binding protein: roles in cellular responsiveness to
      growth hormone].
AB  - In most species, the structure of the growth hormone-binding protein (GH-BP) is
      identical to that of the growth hormone receptor (GH-R). The affinity (Ka) of the
      GH-BP is however 10 x lower than that of the receptor. Two mechanisms of
      production of the GH-BP have been described: in the human and the rabbit, the GH
      BP is cleaved near the cellular membrane by proteolysis and shed into the
      extracellular compartment while in murine species, the serum GH-BP is produced by
      alternative splicing of the gene coding for the GH receptor. The GH-BP prolongs
      the 1/2 life of plasma GH, dampening the free GH levels during peaks and
      maintaining free hormone levels during troughs via the slow dissociation of GH
      from the complex GH-GHBP. By controlling free GH levels within and between peaks,
      GH-BP would thus play an important role in modulating GH action at the cellular
      level. In several physiological and physiopathological conditions, GH-BP and GH-R
      are coordinately regulated. However, there are situations such as during
      pregnancy or certain periods of development where these 2 proteins are not co
      expressed. Therefore, GH-BP circulating levels do not necessarily represent
      cellular GH-R concentrations. In the rat, GH-BP and GH-R are regulated by
      nutritional and endocrine factors, among those are GH, insulin and gonadal
      steroids. In the human, the mechanism responsible for the increase of the
      circulating GH-BP during infancy is still unknown. Finally, the eventual role of
      GH-BP in transmitting the intracellular message of GH following its binding to
      the receptor is still unknown.

PMID- 7574444
TI  - Surname distribution in France: a distance analysis by a distorted geographical
      map.
AB  - The distribution of surnames in 90 distinct regions in France during two
      successive periods, 1889-1915 and 1916-1940, is analysed from the civil birth
      registers of the 36,500 administrative units in France. A new approach, called
      'Mobile Site Method' (MSM), is developed to allow representation of a surname
      distance matrix by a distorted geographical map. A surname distance matrix
      between the various regions in France is first calculated, then a distorted
      geographical map called the 'surname similarity map' is built up from the surname
      distances between regions. To interpret this map we draw (a) successive map
      contours obtained during the step-by-step distortion process, revealing zones of
      high surname dissimilarity, and (b) maps in grey levels representing the
      displacement magnitude, and allowing the segmentation of the geographical and
      surname maps into 'homogeneous surname zones'. By integrating geography and
      surname information in the same analysis, and by comparing results obtained for
      the two successive periods, the MSM approach produces convenient maps showing:
      (a) 'regionalism' of some peripheral populations such as Pays Basque, Alsace,
      Corsica and Brittany; (b) the presence of preferential axes of communications
      (Rhodanian corridor, Garonne valley); (c) barriers such as the Central Massif,
      Vosges; (d) the weak modifications of the distorted maps associated with the two
      periods studied suggest an extension (but limited) of the tendency of surname
      uniformity in France. These results are interpreted, in the nineteenth- and
      twentieth century context, as the consequences of a slow process of local
      migrations occurring over a long period of time.

PMID- 7574445
TI  - Height, weight and menarcheal age of schoolgirls in Oslo--an update.
AB  - Every fifth year since 1920 measurements of height and weight of the school
      children in Oslo have been centrally processed. We present updates obtained for
      girls in 1980 and 1985, and in addition results on menarche from 1985. The slow
      but steady post-war increase in height seems to approach a plateau. For body
      weight the downward post-war trend has been reversed. Menarcheal age was close to
      the stable level of about 13.3 years observed since 1950. Regression analyses
      indicate a co-variation of weight development and menarche. Differences in height
      between city areas were small, while weight was clearly highest and menarcheal
      age clearly lowest in areas with the lowest average income.

PMID- 7574446
TI  - Diet and behavioural activity in 12-week-old infants.
AB  - Deposition of excess dietary energy occurs if energy intake exceeds expenditure.
      Anthropometric differences between breast-fed and formula-fed infants due to
      differences in energy deposition are frequently reported. It has been suggested
      that infant obesity may result from decreased levels of energy expenditure on
      physical activity. Infant diet may therefore influence energy balance by
      affecting behaviour and hence energy expenditure. Behavioural and motor activity
      of 25 formula-fed and 25 breast-fed infants were compared using activity diaries,
      temperament questionnaires and actometers. There were no anthropometric
      differences between the two groups. The breast-fed infants fed significantly more
      slowly than the formula-fed infants despite taking in similar milk volumes, and
      also fed significantly more frequently. Otherwise there were no significant
      differences between the two groups with respect to the daily time spent awake and
      content, asleep, fussy, or crying, nor with respect to gross motor activity and
      temperament. It is unlikely that energy balance of the two groups differed
      significantly on account of behavioural activity.

PMID- 7574447
TI  - Prediction of adult skinfolds and body mass from infancy through adolescence.
AB  - In this paper age-to-age correlations for the body mass index and for skinfolds
      are evaluated for a sample of normal children studied from birth to adulthood.
      While correlations over larger age spans are modest, they become appreciable from
      childhood to adolescence and from adolescence to adulthood. Correlations are
      consistently higher for boys compared to girls, and only for the former does the
      body mass index correlate better than skinfolds. Significant correlations between
      weight increase in the first year and the adult body mass index were found, as
      well as between the age of 'adiposity rebound' and the adult body mass index.
      However, the small size of the correlations forbids any predictive applications.
      As it turns out, the individual prediction of the adult size of the body mass
      index or of skinfolds is a thorny problem, whatever variables and methods are
      chosen. The precision of such a prediction is very low up to late childhood and
      becomes somewhat better in adolescence. From a positive side, this leaves much
      room for overweight children to improve their state. On the other hand, the
      relative risk for becoming a heavy adult is much increased for those who are
      already heavy as children and adolescents. This underlines the dangers of early
      overweight from an epidemiological viewpoint.

PMID- 7574448
TI  - Consanguinity and reproductive behaviour in a tribal population 'the Baiga' in
      Madhya Pradesh, India.
AB  - We have studied the marriage pattern and reproductive behaviour in a single
      Central Indian primitive tribe, the Baiga. Parents were consanguineous in 34% of
      marriages (19.2% mother's brother's daughter (MBD), 13.1% father's sister's
      daughter (FSD) and 1.7% were double first cross-cousins (DFCC). Fertility levels
      were significantly higher (p < 0.05) in related couples (4.7 offspring/couple)
      than unrelated couples (4.2/couple). Mortality (up to 20 years) was 19%. In the
      offspring of consanguineous couples it was higher (19.7%) than in the offspring
      of unrelated couples (18.6%) but the difference was not statistically
      significant. In consanguineous couples the reproductive period was longer than in
      unrelated couples, probably to allow compensation for increased reproductive
      losses (infant and childhood deaths). The level of social as compared to genetic
      parenting was about 35% as measured by tracking the inheritance of sickle gene,
      and allowance must be made for this in assessing the influence of consanguineous
      marriage on fertility and mortality.

PMID- 7574449
TI  - Knemometry in childhood: a study to compare the precision of two different
      techniques.
AB  - Knemometry is an accurate and non-invasive method of quantifying lower leg length
      changes. It reveals multiple fluctuations in leg length velocity over a short
      period of measurement, and on the basis of this it has been proposed that short
      term growth is saltatory rather than a continuous phenomenon. The technical error
      (TE) of the technique which is generally employed, and which is subject to
      observer bias, ranges from 0.09 to 0.16 mm. This study was undertaken to compare
      the original method (OM) to a modified technique which involved measuring from a
      baseline value of which the operator was not aware; this technique is referred to
      as the random zero method (RM). Over a period of 10 months, 58 subjects were
      measured on 413 occasions. Overall, median TE in the RM group at 0.15 mm (P5-0,
      P95-0.65) was higher than the median TE in the OM group at 0.11 mm (P5-0, P95
      0.37). However, the median TE over the last 3 months of 0.15 mm (P5-0.05, P95
      0.87) was lower than the TE in the preceding 4 months of 0.20 mm (P5-0, P95-0.55)
      (WSR, p = 0.04) pointing towards the presence of an operator learning curve. The
      random zero method is a simple modification of the original method. It reduces
      observer bias but leads to a higher TE, which could explain some of the
      fluctuations seen between frequent knemometric measurements. Some knowledge of
      the length of the training period is important in the design of new studies
      involving knemometry; our data suggest that there should be a learning period of
      about 4 months if knemometry is performed as often as quoted above.

PMID- 7574450
TI  - Human immunodeficiency virus encephalitis and dementia.

PMID- 7574451
TI  - Neurological Lyme disease: is there a true animal model?

PMID- 7574452
TI  - AIDS dementia complex and HIV-1 brain infection: clinical-virological
      correlations.
AB  - To evaluate the presence and distribution of central nervous system infection by
      human immunodeficiency virus type 1 (HIV-1), we used immunohistochemical methods
      to map the HIV-1 p24 core protein in the brains of 55 autopsied patients with
      acquired immunodeficiency syndrome (AIDS). In a subset of 40 of these patients
      who had undergone antemortem neurological evaluation of the AIDS dementia complex
      (ADC), we analyzed the relation between the severities of the viral infection and
      clinical dysfunction. Viral antigen was detected in macrophages and cells with
      morphological and immunohistochemical characteristics of microglia as well as
      multinucleated cells. The distribution of antigen-positive cells preferentially
      involved certain deep brain structures, especially the globus pallidus, other
      basal ganglia nuclei, and the central white matter. Overall, the presence and
      frequency of infected cells were highly correlated with the histological findings
      of multinucleated-cell encephalitis and in general with the clinical ADC stage.
      However, infection was often more limited than might be "anticipated" from the
      severity of patients' clinical dysfunction: Only 61% of patients with at least
      ADC stage 1 had detectable antigen and of these only approximately 30% of the
      brain sections were antigen positive. These results suggest a pathogenetic model
      of ADC where virus- or cell-coded toxins amplify the effect of limited brain
      infection.

PMID- 7574453
TI  - Paroxysmal dyskinesias: clinical features and classification.
AB  - We studied 46 patients with paroxysmal dyskinesia and classified them according
      to phenomenology, duration of attacks, and etiology. There were 13 patients, 7
      females, who had paroxysmal kinesigenic dyskinesia (PKD), 10 with attacks lasting
      5 minutes or less (short lasting) and 3 with attacks lasting longer than 5
      minutes (long lasting). Twenty-six patients, 18 females, had paroxysmal
      nonkinesigenic dyskinesia (PNKD), 9 with short-lasting and 17 with long-lasting
      PNKD. Five patients, 3 females, had paroxysmal exertion-induced dyskinesia (PED),
      3 with short-lasting PED and the other 2 with long-lasting PED. In addition,
      there was 1 patient with paroxysmal hypnogenic dyskinesia (PHD) and 1 with
      paroxysmal superior oblique myokymia. Only 2 patients, 1 with PKD and 1 with PHD,
      had family history of paroxysmal dyskinesias. No specific cause could be
      identified in 21 patients; in the other 23 patients the etiologies included the
      following: psychogenic (9 patients), cerebrovascular diseases (4), multiple
      sclerosis (2), encephalitis (2), cerebral trauma (2), peripheral trauma (2),
      migraine (1), and kernicterus (1). Nine of 10 (90%) patients with PKD improved
      with medications, mostly anticonvulsants, compared with only 7 of 19 (37%) with
      PNKD. This new classification, based chiefly on precipitating events, allowed
      appropriate categorization of the attacks in all our patients with paroxysmal
      dyskinesias.

PMID- 7574454
TI  - Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian
      patients.
AB  - To assess the efficacy of fetal mesencephalic grafts in Parkinson's disease, it
      is important to know if the grafted cells survive and are functional. Positron
      emission tomography (PET) and [18F]fluorodopa ([18F]dopa) have been used to
      demonstrate the survival of the grafted cells, but the relationship of [18F]dopa
      uptake changes in the grafted striatum to motor function remains unclear. We
      investigated this question with 16 serial PET scans in 5 severe parkinsonian
      patients unilaterally grafted in whom we found a significant and progressive
      increase of the [18F]dopa uptake in the grafted putamen. The number of patients
      was too small to assess the sensitivity of [18F]dopa PET scans in individual
      patients. Yet, by analyzing the 16 serial PET scans we found a correlation
      between the [18F]dopa uptake (Ki) in the grafted putamen and the percentage of
      daily time spent "on," suggesting that Ki changes have a functional meaning. In
      addition, the Ki values were correlated with the contralateral finger dexterity
      to the same extent in both the grafted and nongrafted putamen. These results
      indicate that [18F]dopa uptake reflects the motor function of the opposite side
      of the body, similarly in the grafted and ungrafted putamen, at least in terms of
      these tasks. Finally, extrapolating from these correlations offers the suggestion
      that clinical optimal results of the graft could be achieved if the graft brings
      the Ki values in the putamen to about two standard deviations of mean control
      values.

PMID- 7574455
TI  - Decreased single-photon emission computed tomographic [123I]beta-CIT striatal
      uptake correlates with symptom severity in Parkinson's disease.
AB  - Previous studies have utilized single-photon emission computed tomography (SPECT)
      to demonstrate decreased [123I]beta-CIT striatal uptake in idiopathic Parkinson
      disease (PD) patients. The present study extends this work by examining SPECT
      outcome measures in a larger group of PD patients with varying disease severity.
      Twenty-eight L-dopa-responsive PD patients (Hoehn-Yahr stages 1-4) and 27 healthy
      controls had SPECT scans at 18 to 24 hours after injection of [123I]beta-CIT.
      Specific to nondisplaceable striatal uptake ratios (designated V3") were
      correlated with Hoehn-Yahr stage and Unified Parkinson's Disease Rating Scale
      (UPDRS) subscores. Linear discriminant function analyses utilizing striatal
      uptakes, putamen-to-caudate ratios, and ipsilateral-contralateral asymmetry
      indices were performed. Decreased striatal tracer uptake (V3") was correlated
      with total UPDRS score for both contralateral and ipsilateral striatum. Putamen
      uptake was relatively more reduced than caudate with mean putamen:caudate ratios
      of 0.50 +/- 0.17 and 0.82 +/- 0.09 for PD patients and controls, respectively.
      Ipsilateral:contralateral asymmetry was significantly greater in PD patients than
      controls. Discriminant function analysis utilizing V3" for ipsilateral and
      contralateral caudate and putamen correctly classified all 55 cases. These data
      demonstrate marked differences in [123I]beta-CIT SPECT measures in healthy
      controls and PD patients. The significant correlation of SPECT measures with
      motor severity suggests [123I]beta-CIT may be a useful marker of disease severity
      in PD.

PMID- 7574456
TI  - Cerebral transport and metabolism of 1-11C-D-glucose during stepped hypoglycemia.
AB  - Attempts to measure blood-to-brain glucose transport and cerebral glucose
      metabolism with 11C-glucose have been hampered by methods that require jugular
      venous sampling or do not adequately account for the efflux of labeled
      metabolites from the brain. We performed eight positron emission tomography
      studies with 1-11C-D-glucose in macaques at arterial plasma glucose
      concentrations of 8.43 to 1.51 mumol ml-1 (152-27 mg dl-1) using a model that
      includes a fourth rate constant to account for regional egress of all 11C
      metabolites. Values for blood-to-brain glucose influx, cerebral glucose
      metabolism, and brain free glucose concentration agreed closely with values
      obtained in mammals by other investigators. Values for net extraction fraction
      corresponded closely to simultaneously measured arteriovenous values. We
      demonstrated that utilization of a model that includes a fourth rate constant to
      account for regional egress of all 11C-metabolites with positron emission
      tomography and 1-11C-D-glucose provides accurate measurements of blood-to-brain
      glucose transport and cerebral glucose metabolism in vivo without need for
      jugular venous sampling, even under conditions of severe hypoglycemia.

PMID- 7574457
TI  - Overexpression of DM20 messenger RNA in two brothers with Pelizaeus-Merzbacher
      disease.
AB  - Pelizaeus-Merzbacher disease is a rare, sex-linked recessive, dysmyelinating
      disease of the central nervous system that has been associated with mutations in
      the myelin proteolipid protein (PLP) gene. Only 25% of patients studied with
      Pelizaeus-Merzbacher disease have exonic mutations in this gene, the underlying
      cause of the disease in the remaining patients is unknown. The PLP gene encodes
      two major alternatively spliced transcripts called PLP and DM20. PLP messenger
      RNA is specifically expressed in central nervous system tissue, whereas DM20
      messenger RNA is found in central nervous system, cardiac, and other tissues. We
      studied cultured skin fibroblasts from 2 brothers with Pelizaeus-Merzbacher
      disease who exhibited no detectable exonic mutation of the PLP gene. Examination
      of RNA from these cells showed that the level of DM20 messenger RNA is elevated
      sixfold relative to male control skin fibroblasts. An unrelated female carrier,
      also with no detectable exonic mutation, showed a threefold increase in DM20
      messenger RNA in cultured skin fibroblasts. Our findings suggest that in some
      patients, Pelizaeus-Merzbacher disease is caused by overexpression of PLP gene
      transcripts, and that in these families a 50% increase of DM20 messenger RNA in
      females, relative to the increase in affected males, can identify a female
      carrier.

PMID- 7574458
TI  - Localization of subclinical ictal activity by functional magnetic resonance
      imaging: correlation with invasive monitoring.
AB  - Functional magnetic resonance imaging (fMRI) with susceptibility-based contrast
      was used to detect focal changes in cerebral blood flow and metabolism in a
      patient with focal epilepsy. The patient presented with frequent partial motor
      seizures involving his right lower face that spread to produce speech arrest and
      occasionally right arm jerking. Consciousness was never impaired during these
      events. A multislice echoplanar technique was used to acquire 16 contiguous axial
      slices every 4 seconds for 11 minutes. Although no overt seizures were observed
      or reported by the patient during the scanning, a time series analysis of the
      functional data revealed focal signal-intensity changes in the posterior left
      frontal lobe, which correlated well both in duration and spatial localization
      with ictal activity subsequently recorded by invasive electrophysiological
      monitoring. The spatial localization of fMRI was more accurate than
      electroencephalography recorded from a subdural grid in predicting the site of
      successful surgical therapy. These results illustrate the potential of functional
      MRI for localizing seizure foci with high spatial and temporal resolution. Such
      studies can be readily combined with high-resolution anatomical imaging, task
      activation studies, and other magnetic resonance techniques.

PMID- 7574459
TI  - Urinary myelin basic protein-like material as a correlate of the progression of
      multiple sclerosis.
AB  - In the multicenter, randomized, placebo-controlled trial of alternate-day
      injections of recombinant interferon beta-1b in relapsing-remitting multiple
      sclerosis (MS), urine specimens were collected periodically from all patients (n
      = 64) in two of the clinical test sites over the 2 years of the study. Urine
      specimens were also collected over two consecutive 24-hour periods from 43
      patients from a third center. Urine samples were assayed for their content of
      myelin basic protein-like material (MBPLM), the level of which was correlated
      with clinical changes, cranial magnetic resonance imaging results, and the
      development of progressive disease. Concordant changes in creatinine values
      affected some of the relationships of MBPLM. The level of urinary MBPLM
      correlated with a chronic progressive course and with the number of lesions and
      the total lesion area on cranial magnetic resonance images. A rise in the level
      of urinary MBPLM appeared to antedate the clinical transition from a relapsing
      remitting to a chronic progressive course. By chance, the randomized entry of
      patients led to significant differences in urinary MBPLM levels among the three
      treatment groups, thus precluding correlation studies of treatment effects.
      However, the patient group from which 24-hour specimens were collected showed
      that the patients with relapsing-remitting MS changing to a chronic progressive
      course, and more specifically, those patients with chronic progressive MS
      receiving placebo, had the highest values of urinary MBPLM. These findings
      indicate that urinary MBPLM may offer an objective test and possibly serve as a
      surrogate marker for detecting or predicting the failure of remission or the
      transition to a progressive phase of MS.

PMID- 7574460
TI  - Autosomal dominant rolandic epilepsy and speech dyspraxia: a new syndrome with
      anticipation.
AB  - We describe a family of 9 affected individuals in three generations with
      nocturnal oro-facio-brachial partial seizures, secondarily generalized partial
      seizures, and centro-temporal epileptiform discharges, associated with oral and
      speech dyspraxia and cognitive impairment. The speech disorder was prominent, but
      differed from that of Landau-Kleffner syndrome and of epilepsy with continuous
      spike and wave during slow-wave sleep. The electroclinical features of this new
      syndrome of autosomal dominant rolandic epilepsy resemble those of benign
      rolandic epilepsy, a common inherited epilepsy of childhood. This family shows
      clinical anticipation of the seizure disorder, the oral and speech dyspraxia, and
      cognitive dysfunction, suggesting that the genetic mechanism could be expansion
      of an unstable triplet repeat. Molecular studies on this syndrome, where the
      inheritance pattern is clear, could also be relevant to identifying a gene for
      benign rolandic epilepsy where anticipation does not occur and the mode of
      inheritance is uncertain.

PMID- 7574461
TI  - Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with
      Alzheimer's disease.
AB  - In this clinical study the cerebrospinal fluid (CSF) level of a novel form of the
      beta-amyloid peptide (A beta) extending to position 42 (A beta 42) was determined
      in patients with Alzheimer's disease (AD) as well as controls. In addition to
      measurement of CSF A beta 42 levels, total A beta peptides, microtubule
      associated protein tau, and apolipoprotein E (ApoE) genotype were also assessed.
      It is interesting that CSF A beta 42 levels were found to be significantly lower
      in AD patients relative to controls, whereas total A beta levels were not. A beta
      42 has recently been shown to preferentially deposit in the brain tissue of
      patients with AD, suggesting that diminished clearance may account for its
      reduction in CSF. As previously reported, tau levels were increased in AD
      patients; however, neither A beta 42 nor tau levels were apparently influenced by
      the ApoE genotype.

PMID- 7574462
TI  - Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease.
AB  - Cerebrospinal fluid from 70 patients with Alzheimer's disease (AD) and 96
      patients with non-AD neurological diseases as well as 19 normal control subjects
      was surveyed by sandwich enzyme-linked immunosorbent assay to quantitate levels
      of the microtubule-associated protein tau in cerebrospinal fluid. The tau level
      was significantly increased in AD patients as compared with that in patients with
      non-AD neurological diseases and control subjects. Increased tau levels were
      found irrespective of age at onset, apolipoprotein E genotype, and clinical
      stage. Western blots of AD cerebrospinal fluid proteins revealed two to three tau
      immunoreactive bands with an apparent molecular mass between 50 and 65 kd
      consistent with phosphorylated cerebrospinal fluid tau. Taken together, our
      results suggest that cerebrospinal fluid tau might reflect the progressive
      accumulation of altered tau due to the progressive death of neurons in the AD
      brain, and that the enzyme-linked immunosorbent assay of cerebrospinal fluid tau
      may prove to be a reliable and early diagnostic test for AD.

PMID- 7574463
TI  - The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's
      disease.
AB  - Both genetic and environmental factors affect the progression of Alzheimer's
      disease (AD). The presence of cortical Lewy bodies in AD patients is associated
      with an altered presentation of AD pathology suggestive of an interaction between
      the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele
      is often present in patients with Lewy body diseases (Parkinson's disease and
      Lewy body variant of AD), we extended these prior observations by studying the
      neuropathology associated with the presence of the CYP2D6B mutant allele in a
      pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B
      mutant allele, in comparison with those without the CYP2D6B allele, were found to
      have a smaller decline in two synaptic markers, choline acetyltransferase and
      synaptophysin, in the frontal cortex relative to normal control values. On the
      other hand, senile plaques and neurofibrillary tangles were not significantly
      affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD
      patients. Association of the CYP2D6B mutant allele with Lewy body formation in
      both Parkinson's disease and the Lewy body variant of AD and with the milder
      synaptic pathology in pure AD without Lewy bodies suggest that depending on the
      contribution of other genetic and environmental factors, this mutant allele may
      be involved with different aspects of neurodegeneration.

PMID- 7574464
TI  - Aphasia in acute stroke: incidence, determinants, and recovery.
AB  - Knowledge of the frequency and remission of aphasia is essential for the
      rehabilitation of stroke patients and provides insight into the brain
      organization of language. We studied prospectively and consecutively an
      unselected and community-based sample of 881 patients with acute stroke.
      Assessment of aphasia was done at admission, weekly during the hospital stay, and
      at a 6-month follow-up using the aphasia score of the Scandinavian Stroke Scale.
      Thirty-eight percent had aphasia at the time of admission; at discharge 18% had
      aphasia. Sex was not a determinant of aphasia in stroke, and no sex difference in
      the anterior-posterior distribution of lesions was found. The remission curve was
      steep: Stationary language function in 95% was reached within 2 weeks in those
      with initial mild aphasia, within 6 weeks in those with moderate, and within 10
      weeks in those with severe aphasia. A valid prognosis of aphasia could be made
      within 1 to 4 weeks after the stroke depending on the initial severity of
      aphasia. Initial severity of aphasia was the only clinically relevant predictor
      of aphasia outcome. Sex, handedness, and side of stroke lesion were not
      independent outcome predictors, and the influence of age was minimal.

PMID- 7574465
TI  - Neuroborreliosis in the nonhuman primate: Borrelia burgdorferi persists in the
      central nervous system.
AB  - Neurological involvement in Lyme disease is common, and is frequently difficult
      to diagnose and treat. Little is known about the fate of the causative spirochete
      Borrelia burgdorferi in the central nervous system (CNS). To determine the
      frequency of parenchymal infection and to determine localization of the organism,
      polymerase chain reaction/hybridization assays were performed in a newly
      described model of Lyme neuroborreliosis in nonhuman primates infected with B.
      burgdorferi. Polymerase chain reaction/hybridization of CNS tissues from 5
      infected nonhuman primates was performed. Substantial amounts of B. burgdorferi
      DNA were detected in the CNS in all infected animals, with a predilection toward
      subtentorial structures. These data suggest that Lyme neuroborreliosis represents
      persistent infection with B. burgdorferi.

PMID- 7574466
TI  - Safety of intravenous valproate.
AB  - This multicenter, open-label trial was designed to study the safety of
      intravenous (IV) sodium valproate in patients with epilepsy. All 318 patients
      (previously treated with antiepileptic drugs) were hospitalized for seizure
      control or anticipated seizures. The protocol allowed physicians to set the
      number of infusions and treatment duration. Adverse events, laboratory studies
      performed, and seizure activity were documented on case report forms. The
      patients' mean age was 34.4 years (range, 2-87 years). The most common reason for
      admission was lack of seizure control (235 patients, 185 of whom were admitted
      for video-electroencephalographic monitoring). The median dosage of valproate was
      375 mg infused over 1 hour. The median number of doses was four, given over 2
      days. In 54 patients (17%), transient adverse events were reported. The most
      frequent were headache, reaction at the injection site, and nausea (2.2% each);
      somnolence (1.9%); vomiting (1.6%); and dizziness and taste perversion (1.3%
      each). No persistent or severe hematologic or serum chemistry abnormalities were
      found. Vital signs were not significantly affected by the IV infusion of
      valproate. At the dosages and rates of administration studied, intravenous
      valproate appears to be safe and well tolerated.

PMID- 7574467
TI  - Selective expansion and long-term culture of human Schwann cells from sural nerve
      biopsies.
AB  - Fragments of sural nerve biopsy specimens were cultured in the presence of the
      supernatant of lymphokine-activated killer cells, resulting in the selective
      outgrowth of cells with bipolar or tripolar morphology, reminiscent of that of
      Schwann cells. Immunofluorescent staining with antibodies to the S-100 protein,
      the low-affinity nerve growth factor receptor, and the surface Thy-1 antigen
      confirmed that these cultures contained more than 99% Schwann cells and no
      detectable fibroblasts. The mitotic activity of Schwann cells was measured by
      bromodeoxyuridine labeling, and was increased when the cells were grown in medium
      with lymphokine-activated killer cell supernatant compared with medium without
      this supernatant. In the presence of lymphokine-activated killer cell
      supernatant, Schwann cells could be maintained in continuous culture for a
      minimum of 8 months.

PMID- 7574468
TI  - Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's
      disease.
AB  - The effect of the apolipoprotein E (APOE) epsilon 4 allele on age of onset was
      analyzed in two groups of families with early-onset Alzheimer's disease (AD), (1)
      Volga German (VG) kindreds, in which AD is caused by an unknown locus and (2)
      early-onset non-VG families showing evidence of linkage to chromosome 14. The
      epsilon 4 allele did not have a detectable effect on age of onset in either
      group. This finding suggests some forms of early-onset familial AD are not
      modifiable by APOE status, or that AD can be caused by APOE-independent pathways.

PMID- 7574469
TI  - Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood.
AB  - Alternating hemiplegia of childhood is an uncommon disease characterized by
      repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but
      attention recently has focused on possible mitochondrial abnormalities. Using 31P
      magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients
      with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during
      incremental aerobic exercise and recovery. There were no significant differences
      in resting muscle between patients and a control group aged 7 to 42 (mean, 19)
      years. Exercise performance was grossly impaired in the patients, the mean
      duration being 30% of normal. The total change in pH during exercise was somewhat
      less than in control subjects, while the changes in phosphocreatine concentration
      and intracellular ADP were similar. Thus the average overall rate of fall of
      phosphocreatine concentration during exercise was three-fold greater than in
      control subjects. However, the initial rate of ATP turnover at the start of
      exercise (a measure of muscle mass and efficiency) was not abnormal. During
      recovery, both the initial rate of phosphocreatine resynthesis and the calculated
      mitochondrial capacity were reduced by about 35%. This mitochondrial defect
      probably explains most of the abnormalities seen during exercise.

PMID- 7574470
TI  - Dopa-responsive parkinsonism phenotype of Machado-Joseph disease: confirmation of
      14q CAG expansion.
AB  - The subtype IV of Machado-Joseph disease (MJD), characterized by parkinsonism
      variably combined with ataxia, distal atrophy, and sensory loss, has been all but
      ignored in recent reports of MJD, including those describing the molecular
      biologic substrate of the disease. We have demonstrated expansion of the CAG
      trinucleotide repeat of the MJD1 gene located on chromosome 14q32.1 in 2 patients
      of Azorean descent who presented with levodopa-responsive atypical parkinsonism.
      Previous publications have documented the presence of this expanded repeat in the
      other more common MJD phenotypes (I-III). To our knowledge, this is the first
      molecular biologic confirmation of the presence of the MJD1 gene in the subtype
      IV phenotype. Patients presenting with parkinsonism and peripheral neuropathy
      should be screened for this genetic defect.

PMID- 7574471
TI  - Reversible dementia and apparent brain atrophy during valproate therapy.
AB  - Two children developed severe cognitive and behavioral deterioration suggestive
      of a degenerative disease while being treated with sodium valproate for
      idiopathic, localization-related epilepsy with centrotemporal spikes. Magnetic
      resonance imaging revealed marked central and generalized cortical and cerebellar
      atrophy. In both patients, clinical symptoms and signs cleared in a few weeks
      following valproate withdrawal. The magnetic resonance imaging appearance
      improved within 3 months in 1 of the patients and normalized in both after 6 and
      12 months. No metabolic changes were associated with the clinical or imaging
      abnormalities. Although the mechanism of this rare idiosyncratic complication of
      valproate therapy is unknown, we advocate discontinuing valproate therapy in all
      epileptic patients with neuromental deterioration or brain atrophy of unknown
      etiology.

PMID- 7574472
TI  - Oxidative damage to protein in sporadic motor neuron disease spinal cord.
AB  - The recent discovery that defects in the gene encoding copper-zinc superoxide
      dismutase (SOD1) are associated with some cases of familial motor neuron disease
      has heightened interest in the possibility that free radical mechanisms may
      contribute to selective motor neuron injury. Sporadic and familial motor neuron
      diseases are clinically and pathologically very similar and may share common
      pathophysiological mechanisms. Thus the role of free radical mechanisms as a
      contributory factor to motor neuron injury in the common sporadic form of motor
      neuron disease requires urgent exploration, particularly as this may provide an
      avenue for therapy aimed at retarding pathological progression. We investigated
      oxidative damage to proteins in the lumbar spinal cord by quantifying the protein
      carbonyl level from 19 patients with sporadic motor neuron disease, 8
      neurologically normal control subjects, and 11 neurological disease control
      subjects, most of whom had slowly progressive neurodegenerative disease. In
      sporadic motor neuron disease the mean protein carbonyl level in the spinal cord
      was increased by 119% (p < 0.02) compared to normal control subjects and by 88%
      (p < 0.04) compared to the neurological disease control subjects. These data
      contribute to the emerging evidence that oxidative damage may play a contributory
      role in the neuronal death in sporadic motor neuron disease. This mechanism may
      be particularly important in a subset of patients with motor neuron disease.

PMID- 7574473
TI  - Re: Absence of postoperative hyponatremia in young women.

PMID- 7574474
TI  - Postanoxic coma: good recovery despite myoclonus status.

PMID- 7574475
TI  - Apolipoprotein E epsilon 4 and fatal cerebral amyloid angiopathy associated with
      dementia pugilistica.

PMID- 7574476
TI  - To be there when the picture is painted.

PMID- 7574477
TI  - Selectin-carbohydrate interactions and the initiation of the inflammatory
      response.
AB  - The orderly migration of various white blood cell types to inflammatory sites is
      a highly regulated process that involves a diversity of adhesion and signaling
      molecules. This cellular influx is initiated by relatively low affinity
      interactions that allow for leukocytes to roll along the vascular surface. This
      rolling phenomenon is mediated by adhesive interactions between lectin containing
      adhesion molecules, termed selectins, on both the vascular endothelium and
      leukocytes, and carbohydrate ligands immobilized on mucin-like scaffolds. This
      adhesion allows for a rapid recognition of various cell types under the
      conditions of vascular flow, with the result that inflammatory cells are
      specifically decelerated adjacent to sites of inflammation. This review focuses
      on the various biochemical aspects of the interactions between the selectins and
      their cognate carbohydrate ligands, with an emphasis on the importance of these
      adhesive events to the inflammatory response.

PMID- 7574478
TI  - DNA processing reactions in bacterial conjugation.
AB  - Bacterial conjugation is an important source of genetic plasticity. The
      initiation complex for conjugative transfer of transmissible plasmids--the
      relaxosome--is a specific DNA-protein structure that has been isolated from cells
      and reconstituted from purified components in vitro. Complexes containing
      uncleaved DNA and DNA cleaved at the nicsite in the origin of transfer (oriT)
      coexist in equilibrium. Relaxase is usually loaded onto oriT by accessory DNA
      binding proteins. Relaxase catalyzes cleavage of a specific phosphodiester bond
      at nic and becomes covalently linked through a tyrosyl residue to the 5' terminus
      of the cleaved strand. Cleaved DNA may be unwound for transfer by a plasmid
      encoded helicase. Single-strand transfer is thought to occur by a replicative
      rolling circle mechanism. Termination of a round of transfer is achieved by the
      cleaving-joining activity of the relaxase linked to the 5' end of the
      transferring strand. Relationships between DNA processing reactions and
      conjugative interactions of cell envelopes are particularly obscure aspects of
      the conjugation cycle.

PMID- 7574479
TI  - DNA polymerase III holoenzyme: structure and function of a chromosomal
      replicating machine.
AB  - DNA polymerase III holoenzyme contains two DNA polymerases embedded in a particle
      with 9 other subunits. This multisubunit DNA polymerase is the Eschericia coli
      chromosomal replicase, and it has several special features that distinguish it as
      a replicating machine. For example, one of its subunits is a circular protein
      that slides along DNA while clamping the rest of the machinery to the template.
      Other subunits act together as a matchmaker to assemble the ring onto DNA.
      Overall, E. coli DNA polymerase III holoenzyme is very similar in both structure
      and function to the chromosomal replicases of eukaryotes, from yeast all the way
      up to humans. This review summarizes our present knowledge about the function of
      the 10 subunits of this replicating machine and how they coordinate their actions
      for smooth duplication of chromosomes.

PMID- 7574480
TI  - The roles of retinoids in vertebrate development.
AB  - Several lines of experimentation suggest that endogenous retinoids, metabolites
      of vitamin A, play a role in the anterior/posterior development of the central
      body axis and the limbs of vertebrates. High levels of endogenous retinoids have
      been detected in proximity to these developing axes in a variety of vertebrate
      fetuses. Teratogenesis studies suggest that both retinoid excess and deficiency
      are capable of disrupting the development of these axes. Finally, retinoic acid
      receptors regulate many developmental control genes, including homeobox genes and
      growth factor genes.

PMID- 7574481
TI  - Plasma lipid transfer proteins.
AB  - The plasma lipid transfer proteins mediate the transfer and exchange of
      phospholipids and neutral lipids between the plasma lipoproteins. The cholesteryl
      ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) are
      members of the lipid transfer/lipopolysaccharide binding gene family. The CETP
      contains binding sites for cholesteryl ester and triglycerides and probably acts
      by a carrier-mediated mechanism. The CETP mediates catabolism of HDL cholesteryl
      esters, with secondary decreases in HDL size and protein content. The CETP plays
      a central role in reverse cholesterol transport i.e. the centripetal movement of
      cholesterol from the periphery back to the liver. CETP gene expression is
      upregulated in response to increased dietary cholesterol or endogenous
      hypercholesterolemia. Although CETP reduces HDL levels, its role in reverse
      cholesterol transport suggests a dominant anti-atherogenic action in vivo.

PMID- 7574482
TI  - The molecular biology of hepatitis delta virus.
AB  - Hepatitis delta virus (HDV) contains a circular, viroid-like RNA genome, the only
      animal viral RNA of its kind. It possesses a ribozyme activity, which can
      autocatalytically cleave and ligate itself. The ribozyme has a unique structural
      requirement different from other known ribozymes. HDV RNA undergoes RNA-dependent
      RNA replication via a double rolling circle mechanism, which is probably mediated
      by cellular RNA polymerase II, utilizing modified cellular transcription
      machineries. HDV RNA encodes a single protein, hepatitis delta antigen, which is
      a nuclear, RNA-binding phosphoprotein and required for viral RNA replication.
      During replication, HDV RNA undergoes a specific RNA editing event to extend its
      open reading frame and produce a longer, isoprenylated delta antigen, which
      suppresses RNA replication and initiates viral particle assembly. Ribozyme, cell
      mediated RNA-dependent RNA replication, and RNA editing are some of the unique
      properties and unresolved issues of the molecular biology of HDV.

PMID- 7574483
TI  - The multiplicity of domains in proteins.
AB  - The domainal nature of proteins is well established. What is less certain is how
      many domains are evolutionarily mobile in that they occur in otherwise
      nonhomologous proteins or in different sequential locations in homologous
      proteins. The combinatorial advantage of shuffling domains around into diverse
      settings is obvious. Those domains that have been shuffled about in recent
      evolutionary times, within the last half billion years or so, can usually be
      identified on the basis of sequence resemblances alone. Contrarily, domains that
      were rearranged in ancient times may only be apparent after three-dimensional
      analysis, their sequence resemblances having been eroded over time. The shuffling
      of domains in recently evolved proteins has been greatly promoted by introns, but
      this does not imply that all domainal rearrangements involve introns. Only a
      small fraction of known exons show evidence of having been shuffled. Taken in
      aggregate, the available data best fit a scenario whereby a relative small number
      of genes encoding domain-sized polypeptides has been expanded by duplication and
      modification with a burst of exceptional genomic rearrangement.

PMID- 7574484
TI  - The envelope of mycobacteria.
AB  - Mycobacteria, members of which cause tuberculosis and leprosy, produce cell walls
      of unusually low permeability, which contribute to their resistance to
      therapeutic agents. Their cell walls contain large amounts of C60-C90 fatty
      acids, mycolic acids, that are covalently linked to arabinogalactan. Recent
      studies clarified the unusual structures of arabinogalactan as well as of
      extractable cell wall lipids, such as trehalose-based lipooligosaccharides,
      phenolic glycolipids, and glycopeptidolipids. Most of the hydrocarbon chains of
      these lipids assemble to produce an asymmetric bilayer of exceptional thickness.
      Structural considerations suggest that the fluidity is exceptionally low in the
      innermost part of bilayer, gradually increasing toward the outer surface.
      Differences in mycolic acid structure may affect the fluidity and permeability of
      the bilayer, and may explain the different sensitivity levels of various
      mycobacterial species to lipophilic inhibitors. Hydrophilic nutrients and
      inhibitors, in contrast, traverse the cell wall presumably through channels of
      recently discovered porins.

PMID- 7574486
TI  - Transcriptional regulation of gene expression during adipocyte differentiation.
AB  - Cell culture models (e.g. 3T3-L1 cells) have been developed for studying the
      process of adipocyte differentiation. Differentiation can be induced by adding
      insulin-like growth factor I, glucocorticoid, fatty acids, and an agent that
      increases intracellular cAMP level. The adipocyte differentiation program is
      regulated by transcriptional activators such as CCAAT/enhancer binding protein
      alpha (C/EBP alpha), peroxisomal proliferator activated receptor gamma 2 (PPAR
      gamma 2), fatty acid activated receptor (FAAR), and transcriptional repressors
      such as preadipocyte repressor element binding protein (PRE) and C/EBP
      undifferentiated protein (CUP). These transcription factors coordinate the
      expression of genes involved in creating and maintaining the adipocyte phenotype
      including the insulin-responsive glucose transporter (GLUT4), stearoyl CoA
      desaturase 1 (SCD1), and the fatty acid binding protein (422/aP2).

PMID- 7574485
TI  - Eukaryotic phospholipid biosynthesis.
AB  - The current status of the biochemistry of phospholipid biosynthesis is presented.
      The review focuses on the identification and characterization of molecular tools
      such as purified enzymes and cloned genes and cDNAs for those enzymes. The
      enzymes discussed are those involved in the biosynthesis of the major
      phospholipid classes, namely, phosphatidate, phosphatidylserine,
      phosphatidylethanolamine, phosphatidylcholine, sphingomyelin,
      phosphatidylinositol and its phosphorylated derivatives, and cardiolipin. The
      review centers on the pathways in mammals and yeast. Novel genetic approaches
      used to delineate pathways and clone cDNAs are discussed. The regulatory roles
      played by some of the enzymes involved in controlling the biosynthetic pathways
      are presented.

PMID- 7574487
TI  - Human carbonic anhydrases and carbonic anhydrase deficiencies.
AB  - Carbonic anhydrases (CAs I-VII) are products of a gene family that encodes seven
      isozymes and several homologous, CA- related proteins. All seven isozymes have
      been cloned, sequenced, and mapped, and the intron-exon organization of five
      genes established. They differ in subcellular localizations, being cytoplasmic
      (CA I, II, III, and VII), GPI-anchored to plasma membranes of specialized
      epithelial and endothelial cells (CA IV), in mitochondria (CA V), or in salivary
      secretions (CA VI). They also differ in kinetic properties, susceptibility to
      inhibitors, and tissue-specific distribution. Structural and kinetic studies of
      recombinant natural and mutant CAs have greatly increased our understanding of
      the structural requirements for catalysis. Studies of the effects of CA
      inhibitors over many years have implicated CAs in a variety of physiological
      processes. Analyses of human and animal CA deficiencies provide unique
      opportunities to understand the individual contributions of different isozymes to
      these processes.

PMID- 7574488
TI  - Collagens: molecular biology, diseases, and potentials for therapy.
AB  - The collagen superfamily of proteins now contains at least 19 proteins formally
      defined as collagens and an additional ten proteins that have collagen-like
      domains. The most abundant collagens form extracellular fibrils or network-like
      structures, but the others fulfill a variety of biological functions. Some of the
      eight highly specific post-translational enzymes involved in collagen
      biosynthesis have recently been cloned. Over 400 mutations in 6 different
      collagens cause a variety of human diseases that include osteogenesis imperfecta,
      chondrodysplasias, some forms of osteoporosis, some forms of osteoarthritis, and
      the renal disease known as the Alport syndrome. Many of the disease phenotypes
      have been produced in transgenic mice with mutated collagen genes. There has been
      increasing interest in the possibility that the unique post-translational enzymes
      involved in collagen biosynthesis offer attractive targets for specifically
      inhibiting excessive fibrotic reactions in a number of diseases. A number of
      experiments suggest it may be possible to inhibit collagen synthesis with oligo
      nucleotides or antisense genes.

PMID- 7574489
TI  - Structure and activities of group II introns.
AB  - Group II introns are found in eubacteria and eubacterial-derived, organellar
      genomes. They have ribozymic activities, by which they direct and catalyze the
      splicing of the exons flanking them. This chapter reviews the secondary structure
      and known tertiary interactions of the ribozymic component of group II introns in
      relation to the problems of specifying splice sites and building a catalytic
      core. We pay special attention to the relationship between the
      transesterification and hydrolytic modes of initiating splicing and the
      stereospecificities of these reactions. A number of group II introns encode
      proteins of the reverse transcriptase family; the activity of these proteins
      enables the host introns to change genomic locations by mechanisms that are only
      beginning to be deciphered. Finally, we briefly discuss multipartite and post
      transcriptionally edited group II introns, together with the intron microcosm of
      Euglena gracilis chloroplasts and the possible relationships between group II and
      spliceosome-catalyzed splicing processes.

PMID- 7574490
TI  - Generation, translocation, and presentation of MHC class I-restricted peptides.
AB  - The T lymphocytes of the vertebrate immune system look for changes that take
      place within the organism by examining a display of peptides at the cell surface.
      These peptides are presented by the products of the major histocompatibility
      complex (MHC). MHC class I products present peptides derived by proteolysis of
      cytosolic proteins by the multicatalytic protease, the proteasome. These peptides
      are translocated from the cytosol into the endoplasmic reticulum by a dedicated
      peptide transporter, the transporter associated with antigen presentation (TAP).
      TAP consists of two subunits, and translocates peptides that are approximately 8
      12 residues in length. The COOH terminal residue of the peptide is a major
      determinant in the specificity of translocation. Following translocation,
      peptides bind to MHC class I molecules, which depend on the peptide ligand as
      well as on interactions with chaperonins for proper folding. These complexes then
      egress from the ER and are transported to their final destination, the cell
      surface.

PMID- 7574491
TI  - Structure and function of voltage-gated ion channels.
AB  - Voltage-gated ion channels are responsible for generation of electrical signals
      in cell membranes. Their principal subunits are members of a gene family and can
      function as voltage-gated ion channels by themselves. They are expressed in
      association with one or more auxiliary subunits which increase functional
      expression and modify the functional properties of the principal subunits.
      Structural elements that are required for voltage-dependent activation, selective
      ion conductance, and inactivation have been identified, and their mechanisms of
      action are being explored through mutagenesis, expression in heterologous cells,
      and functional analysis. These experiments reveal that this family of channels is
      built upon a common structural theme with variations appropriate for functional
      specialization of each channel type.

PMID- 7574492
TI  - Common themes in assembly and function of eukaryotic transcription complexes.
AB  - Eukaryotes contain three distinct RNA polymerase enzymes, each responsible for
      the transcription of a subclass of nuclear genes. Despite this division of labor,
      each RNA polymerase system follows a common blueprint to execute the loading of
      the polymerase onto the relevant promoter region. The RNA polymerase II system
      appears unique in that after RNA polymerase II has loaded onto the DNA, two
      auxiliary factors, TFIIE and TFIIH, are necessary for its escape from the
      promoter region. The complexity of the RNA polymerase II initiation pathway
      provides a multitude of potential targets for transcriptional activators. Tight
      control over transcription initiation levels is afforded by multiple cofactors
      that both enhance and repress.

PMID- 7574493
TI  - How glycosylphosphatidylinositol-anchored membrane proteins are made.
AB  - Glycosylphosphatidylinositol (GPI) linkage is a fairly common means of anchoring
      membrane proteins to eukaryotic cells, although the exact function of the GPI
      linkage is not clear. The nascent form of a typical GPI protein contains a
      hydrophobic NH2-terminal signal peptide that directs it to the ER. There the
      signal peptide is removed by NH2-terminal signal peptidase. Nascent forms of GPI
      linked proteins contain a second hydrophobic peptide at their COOH terminus. The
      COOH-terminal peptide is also removed during processing and the GPI moiety is
      ultimately linked to what had been an internal sequence in the nascent protein.
      Two independent pathways are involved in the biosynthesis of GPI proteins, GPI
      formation, and processing of the nascent protein with attachment of the GPI
      moiety. Studies in whole cells and in cell-free systems indicate that structural
      requirements around the COOH-terminal cleavage site of nascent proteins are
      similar to those at the cleavage site of NH2-terminal signal peptidase. However,
      COOH-terminal processing requires a transmidase for which evidence is presented
      as well as a proposed mechanism of its action.

PMID- 7574494
TI  - Protein-RNA recognition.
AB  - Specific interactions between RNAs and proteins are fundamental to many cellular
      processes, including the assembly and function of ribonucleoprotein particles
      (RNPs), such as ribosomes and spliceosomes and the post-transcriptional
      regulation of gene expression. Among the complexes studied to date are small RNAs
      bound to individual amino acids, tRNAs and tRNA fragments bound to their cognate
      aminoacyl-tRNA synthetases, and a variety of proteins bound to RNA single
      strands, hairpins, irregular helices, and tertiary structures stabilized by bound
      cations. Several proteins use a beta-sheet surface to bind RNAs, and others
      insert an alpha-helix into the widened major groove of a non-canonical RNA helix.
      Distortion or rearrangement of the RNA structure by bound protein is a common
      theme. The structural details of protein-RNA complexes are being resolved by
      nuclear magnetic resonance (NMR) and X-ray crystallography, but thorough
      thermodynamic analyses of recognition mechanisms have yet to be performed.

PMID- 7574495
TI  - Transcriptional responses to polypeptide ligands: the JAK-STAT pathway.
AB  - Cytokines and growth factors regulate multiple aspects of cell growth through
      their interactions with specific receptors. These receptors initiate signals
      directed at both the cytoplasmic and the nuclear compartments. Many of the
      nuclear signals culminate in the induction of new genes. Characterization of the
      ability of IFN-alpha to rapidly induce new genes has led to the identification of
      a new signaling paradigm, the JAK-STAT (Signal Transducers and Activators of
      Transcription) pathway. In the IFN-alpha pathway, two receptor associated
      tyrosine kinases from the JAK family, Jak1 and Tyk2, mediate the activation of
      two latent cytoplasmic transcription factors, Stat1 and Stat2. More recent
      studies have not only determined that this pathway is used extensively, but have
      led to the identification of additional components (e.g., Jak2, Jak3, Stat3,
      Stat4, Stat5, and Stat6). This review will examine how these components mediate
      the transduction of signal directly from receptor to nucleus.

PMID- 7574496
TI  - Triplex DNA structures.
AB  - A DNA triplex is formed when pyrimidine or purine bases occupy the major groove
      of the DNA double Helix forming Hoogsteen pairs with purines of the Watson-Crick
      basepairs. Intermolecular triplexes are formed between triplex forming
      oligonucleotides (TFO) and target sequences on duplex DNA. Intramolecular
      triplexes are the major elements of H-DNAs, unusual DNA structures, which are
      formed in homopurine-homopyrimidine regions of supercoiled DNAs. TFOs are
      promising gene-drugs, which can be used in an anti-gene strategy, that attempt to
      modulate gene activity in vivo. Numerous chemical modifications of TFO are known.
      In peptide nucleic acid (PNA), the sugar-phosphate backbone is replaced with a
      protein-like backbone. PNAs form P-loops while interacting with duplex DNA
      forming triplex with one of DNA strands leaving the other strand displaced. Very
      unusual recombination or parallel triplexes, or R-DNA, have been assumed to form
      under RecA protein in the course of homologous recombination.

PMID- 7574497
TI  - Interfacial enzymology of glycerolipid hydrolases: lessons from secreted
      phospholipases A2.
AB  - Interfacial enzymes operate at an organized interface such as lipid aggregates in
      contact with the aqueous phase. The enzyme phospholipase A2 is a well studied
      interfacial enzyme, and a discussion of its behavior at interfaces is the topic
      of this review. Knowledge gained from studies of phospholipases A2 can be applied
      toward the quantitative analysis of other interfacial enzymes. The kinetic
      analysis of these enzymes is greatly simplified if one establishes certain
      experimental conditions that limit the exchange of enzyme and substrate between
      different substrate aggregates. With such constraints, the kinetics can be
      analyzed in terms of classical Michaelis-Menten theory adopted for the action of
      enzymes at interfaces. It is also possible to describe other enzyme properties
      such as inhibition and substrate preferences in a meaningful way using formalism
      that is well known in solution-phase enzymology.

PMID- 7574498
TI  - Metabolic coupling factors in pancreatic beta-cell signal transduction.
AB  - This chapter focuses on the biochemical mechanisms that mediate glucose
      stimulated insulin secretion (GSIS) from beta-cells of the islets of Langerhans
      and the potentiating role played by fatty acids. We summarize evidence supporting
      the idea that glucose metabolism is required for GSIS and that the GLUT-2
      facilitated glucose transporter and the glucose phosphorylating enzyme
      glucokinase play important roles in measuring changes in extracellular glucose
      concentration. The idea that glucose metabolism is linked to insulin secretion
      through a sequence of events involving changes in ATP:ADP ratio, inhibition of
      ATP-sensitive K+ channels, and activation of voltage-gated Ca2+ channels is
      critically reviewed, and the relative importance of ATP generated from glycolytic
      versus mitochondrial metabolism is evaluated. We also present the growing concept
      that an important signal for insulin secretion may reside at the linkage between
      glucose and lipid metabolism, specifically the generation of the regulatory
      molecule malonyl CoA that promotes fatty acid esterification and inhibits
      oxidation. Finally, we show that in contrast to its short term potentiating
      effect on GSIS, long-term exposure of islets to high levels of fatty acids
      results in beta-cell dysfunction, suggesting that hyperlipidemia associated with
      obesity may play a causal role in the diminished GSIS characteristic of non
      insulin-dependent diabetes mellitus (NIDDM).

PMID- 7574499
TI  - The catalytic mechanism and structure of thymidylate synthase.
AB  - Thymidylate synthase (TS, EC 2.1.1.45) catalyzes the reductive methylation of
      dUMP by CH2H4folate to produce dTMP and H2folate. Knowledge of the catalytic
      mechanism and structure of TS has increased substantially over recent years.
      Major advances were derived from crystal structures of TS bound to various
      ligands, the ability to overexpress TS in heterologous hosts, and the numerous
      mutants that have been prepared and analyzed. These advances, coupled with
      previous knowledge, have culminated in an in-depth understanding of many
      important molecular details of the reaction. We review aspects of TS catalysis
      that are most pertinent to understanding the current status of the structure and
      catalytic mechanism of the enzyme. Included is a discussion of available sources
      and assays for TS, a description of the enzyme's chemical mechanism and crystal
      structure, and a summary of data obtained from mutagenesis experiments.

PMID- 7574500
TI  - Diversity of oligonucleotide functions.
AB  - SELEX is a technology for the identification of high affinity oligonucleotide
      ligands. Large libraries of random sequence single-stranded oligonucleotides,
      whether RNA or DNA, can be thought of conformationally not as short strings but
      rather as sequence dependent folded structures with high degrees of molecular
      rigidity in solution. This conformational complexity means that such a library is
      a source of high affinity ligands for a surprising variety of molecular targets,
      including nucleic acid binding proteins such as polymerases and transcription
      factors, non-nucleic acid binding proteins such as cytokins and growth factors,
      as well as small organic molecules such as ATP and theophylline. The range of
      applications of this technology for new discovery extends from basic research
      reagents to the identification of novel diagnostic and therapeutic reagents.
      Examples of these applications are described along with a discussion of
      underlying principles and future developments expected to further the utility of
      SELEX.

PMID- 7574501
TI  - 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling
      enzyme.

PMID- 7574502
TI  - Ribonucleosides and RNA.
AB  - Landmark discoveries such as the autocatalytic cleavage activity of certain RNA
      molecules, as well as small oligoribonucletide ribozymes and later the in vitro
      evolution of novel bioactive oligoribonucleotides (SELEX), have created entire
      new fields of biochemical research. The discovery of SELEX has provided a method
      for producing high-affinity nucleic acid ligands with high binding specificity to
      important medicinal targets. Including modified nucleotides into RNA ligands
      derived from SELEX may yield improved RNA therapeutics. The chemistry of
      oligoribonucleotides in comparison to oligodeoxyribonucleotides has led to
      resurgent attention on the role of modified nucleotides in RNA structure and
      function. Such modifications are also employed to impart stability towards
      endonuclease degradation on oligoribonucleotides.

PMID- 7574503
TI  - The nuclear pore complex.
AB  - The nuclear pore complex (NPC) creates an aqueous channel across the nuclear
      envelope through which macromolecular transport between nucleus and cytoplasm
      occurs. Nucleocytoplasmic traffic is bidirectional and involves diverse
      substrates, including protein and RNA. It is unclear whether import and export
      are mechanistically similar, but evidence suggests that numerous pathways may be
      involved. The discovery of filaments that extend out from each side of the NPC
      suggests that the NPC may also have a structural role, perhaps providing a
      connection between cytoskeletal elements of the nucleus and cytoplasm. If this
      suggestion is valid, it remains to be determined whether this aspect of NPC
      function is related to its role in nuclear transport. This review discusses
      recent developments regarding the structure of the NPC, characterization of its
      constituent proteins (nucleoporins), the mechanism by which transport occurs, the
      function of individual nucleoporins, and the pathway of NPC assembly and
      disassembly.

PMID- 7574504
TI  - The small nucleolar RNAs.
AB  - The present review summarizes key progress made in characterizing the small
      nucleolar RNAs (snoRNAs) of eukaryotic cells. Recent studies have shown snoRNA
      populations to be substantially more complex than anticipated initially. Many
      newly discovered snoRNAs are synthesized by an intron-processing pathway, which
      provides a potential mechanism for coordinating nuclear RNA synthesis. Several
      snoRNAs and snoRNP proteins are known to be needed for processing of ribosomal
      RNA, but precise functions remain to be defined. In principle, snoRNAs could have
      several roles in ribosome synthesis including: folding of pre-rRNA, formation of
      rRNP substrates, catalyzing RNA cleavages, base modification, assembly of pre
      ribosomal subunits, and export of product rRNP particles.

PMID- 7574505
TI  - Superoxide radical and superoxide dismutases.
AB  - O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing
      inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH.. SODs
      inhibit such HO. production by scavengingO2-, but Cu, ZnSODs, by virtue of a
      nonspecific peroxidase activity, may peroxidize spin trapping agents and thus
      give the appearance of catalyzing OH. production from H2O2. There is a
      glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to
      acidic glycosamino-glycans. It minimizes the reaction of O2- with NO. E. coli,
      and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may
      serve to protect against extracellular O2-. Mn(III) complexes of multidentate
      macrocyclic nitrogenous ligands catalyze the dismutation of O2- and are being
      explored as potential pharmaceutical agents. SOD-null mutants have been prepared
      to reveal the biological effects of O2-. SodA, sodB E. coli exhibit dioxygen
      dependent auxotrophies and enhanced mutagenesis, reflecting O2(-)-sensitive
      biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD,
      are oxygen intolerant, and the double mutant was hypermutable and defective in
      sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD
      null Drosophila exhibited a shortened lifespan.

PMID- 7574507
TI  - In vitro antileishmanial properties of tri- and pentavalent antimonial
      preparations.
AB  - To better understand the antileishmanial effects of antimonial agents we
      synthesized complexes of tri- and pentavalent antimony with mannan. The 50%
      inhibitory concentrations (IC50s) of these agents, along with those of potassium
      antimony tartrate [Sb(III)] and sodium stibogluconate [Sb(V)], were determined
      for promastigotes and intramacrophage amastigotes. The trivalent antimonial
      agents were more potent than the pentavalent agents. Although the IC50s were 60-
      to more-than-600-fold higher for promastigotes than for amastigotes, similar
      intracellular antimony concentrations in both life forms were measured after
      incubation with all four drugs at their respective IC50s. Macrophages accumulated
      antimony during a 4-h exposure that was retained intracellularly for at least 3
      days. Amastigotes inside macrophages had a higher antimony content 6 days after a
      single 4-h treatment than they did immediately after treatment, suggesting that
      macrophages serve as a reservoir for antimonial agents and prolong parasite
      exposure. Macrophages concentrated antimony from the medium with potassium
      antimony tartrate, trivalent antimony-mannan, and pentavalent antimony-mannan
      treatments. N-Acetylcysteine antagonized the antileishmanial effects of these
      three drugs against intracellular amastigotes; in contrast, it had minimal
      effects on the action of sodium stibogluconate.

PMID- 7574508
TI  - Cefixime penetration in human renal parenchyma.
AB  - The diffusion of cefixime, a new orally active expanded-spectrum cephalosporin,
      was studied in 12 patients undergoing nephrectomy after receiving 200-mg oral
      doses every 12 h for 2 days. The patients were divided into two groups according
      to the time of perioperative sampling after the last dose: 4 h (group 1) and 12 h
      (group 2). Preoperative blood samples were taken just before administration of
      the last dose of cefixime. Simultaneous blood and tissue samples were collected
      perioperatively at 4 h (time to peak level) and 12 h (residual level). The
      intrarenal concentrations of cefixime were measured by an isocratic reversed
      phase high-pressure liquid chromatographic (HPLC) assay. Concentrations in serum
      were determined by both microbiological and HPLC assays. The mean peak levels in
      serum were 3.41 +/- 0.43 micrograms/ml (group 1), and the residual levels
      averaged 1.54 +/- 1.17 micrograms/ml (group 2). The diffusion in renal parenchyma
      was not significantly different in the cortexes and medullas of both groups of
      patients: 5.7 to 6.4 micrograms/g in group 1 and 4.6 to 4.7 micrograms/g in group
      2. The decrease in cefixime concentrations was slower in tissue than in serum;
      the ratios of concentrations in tissue to those in serum were 3.5 to 3.6 and 1.7
      to 1.9 at 4 and 12 h, respectively. The intrarenal concentrations of cefixime
      remained higher than the MIC for the most susceptible gram-negative bacteria
      during the time interval between the administration of two doses.

PMID- 7574509
TI  - Evaluation of CP-99,219, a new fluoroquinolone, for treatment of experimental
      penicillin- and cephalosporin-resistant pneumococcal meningitis.
AB  - CP-99,219 is a new fluoroquinolone that has excellent activity against gram
      positive organisms including penicillin- and cephalosporin-resistant
      Streptococcus pneumoniae strains. In our well-established rabbit model of
      meningitis, we conducted experiments to determine the concentrations of CP-99,219
      in cerebrospinal fluid (CSF) after intravenous administration and its ability to
      eradicate two penicillin-resistant pneumococcal isolates. The peak and trough
      concentrations of CP-99,219 in the CSF were from 19 to 25% of the concentrations
      simultaneously obtained in serum and were unaffected by concomitant dexamethasone
      administration. Compared with untreated (control) animals, three doses of CP
      99,219 given 5 h apart significantly reduced the bacterial count in CSF by 5 to 6
      log10 CFU at 10 h. Although 47% of the dexamethasone-treated animals and 18% of
      those not given the steroid had positive cultures at 24 h (14 h after
      administration of the last antibiotic dose), the mean bacterial counts did not
      change from those observed at 10 h. Additionally, only results for animals
      infected with one of the two pneumococcal strains appeared to be affected by
      concomitant dexamethasone therapy.

PMID- 7574510
TI  - Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected
      patients.
AB  - The pharmacokinetics of cidofovir (HPMPC; (S)-1-[3-hydroxy-2
      (phosphonylmethoxy)propyl]cytosine) were examined at five dose levels in three
      phase I/II studies in a total of 42 human immunodeficiency virus-infected
      patients (with or without asymptomatic cytomegalovirus infection). Levels of
      cidofovir in serum following intravenous infusion were dose proportional over the
      dose range of 1.0 to 10.0 mg/kg of body weight and declined biexponentially with
      an overall mean +/- standard deviation terminal half-life of 2.6 +/- 1.2 h (n =
      25). Approximately 90% of the intravenous dose was recovered unchanged in the
      urine in 24 h. The overall mean +/- standard deviation total clearance of the
      drug from serum (148 +/- 25 ml/h/kg; n = 25) approximated renal clearance (129 +/
      42 ml/h/kg; n = 25), which was significantly higher (P < 0.001) than the
      baseline creatinine clearance in the same patients (83 +/- 21 ml/h/kg; n = 12).
      These data indicate that active tubular secretion played a significant role in
      the clearance of cidofovir. The steady-state volume of distribution of cidofovir
      was approximately 500 ml/kg, suggesting that the drug was distributed in total
      body water. Repeated dosing with cidofovir at 3.0 and 10.0 mg/kg/week did not
      alter the pharmacokinetics of the drug. Concomitant administration of intravenous
      cidofovir and oral probenecid to hydrated patients had no significant effect on
      the pharmacokinetics of cidofovir at a 3.0-mg/kg dose. At higher cidofovir doses,
      probenecid appeared to block tubular secretion of cidofovir and reduce its renal
      clearance to a level approaching glomerular filtration.

PMID- 7574511
TI  - Experimental Streptococcus pneumoniae infection in mice for studying correlation
      of in vitro and in vivo activities of penicillin against pneumococci with various
      susceptibilities to penicillin.
AB  - The purpose of the study was to investigate the correlation of in vitro activity
      with the in vivo effect and the pharmacokinetics of penicillin in the treatment
      of infections with pneumococci with various susceptibilities to penicillin. We
      used 10 pneumococcal strains for which penicillin MICs ranged from 0.016 to 8
      micrograms/ml. Time-kill curve experiments were performed with all strains. We
      found that the effect of penicillin in vitro is concentration independent, with a
      maximum effect at two to four times the MIC for penicillin-susceptible as well as
      penicillin-resistant pneumococci. The mouse peritonitis model with an inoculum of
      approximately 10(6) CFU, to which mucin was added, resulted in a reproducible
      lethal infection with the pneumococci. The 50% effective dose was determined for
      each strain, and we found a highly significant correlation between the log MIC
      and the log 50% effective dose of penicillin against these strains (P < 0.01).
      Furthermore, it was shown that the most important pharmacokinetic parameter
      determining the effect of penicillin in vivo was the time that the concentration
      of penicillin in serum was greater than the MIC.

PMID- 7574506
TI  - A functional classification scheme for beta-lactamases and its correlation with
      molecular structure.

PMID- 7574512
TI  - Pharmacokinetics of dideoxypurine nucleoside analogs in plasma and cerebrospinal
      fluid of rhesus monkeys.
AB  - The pharmacokinetics of 2',3'-dideoxyadenosine (ddA), didanosine, 2',3'
      dideoxyguanosine (ddG), and 6-halogenated prodrugs of ddG, 6-chloro-ddG and 6
      iodo-ddG, in plasma and cerebrospinal fluid (CSF) were studied in a non-human
      primate model. ddA was rapidly and completely deaminated to didanosine, such that
      didanosine concentration profiles in plasma and CSF were identical following
      administration of ddA and didanosine. The mean clearance of didanosine was 0.50
      liters/h/kg, the terminal half-life was 1.8 h, and the CSF-to-plasma ratio was
      4.8%. The disposition of ddG was similar, with a clearance of 0.70 liters/h/kg
      and a half-life of 1.7 h. The adenosine deaminase-mediated conversion of the 6
      halogenated-ddG prodrugs to ddG was rapid but incomplete (48% for 6-chloro-ddG
      and 29% for 6-iodo-ddG). The CSF-to-plasma ratios of ddG with equimolar doses of
      ddG, 6-chloro-ddG, and 6-iodo-ddG were 8.5, 24, and 17%, respectively, but the
      actual ddG exposures in CSF (area under the CSF concentration-time curve) were
      comparable for ddG (12.1 microM.h) and the 6-halogenated-ddG prodrugs (18.8
      microM.h for 6-chloro-ddG, 9.3 microM.h for 6-iodo-ddG).6-Chloro-ddG was not
      detectable in plasma or CSF, and the CSF-to-plasma ratio of 6-iodo-ddG was 9.4%,
      so the higher CSF-to-plasma ratios of ddG with the administration of the 6
      halogenated-ddG prodrugs does not appear to be the result of enhanced penetration
      of the prodrug and subsequent dehalogenation to ddG. The penetration of ddG into
      CSF exceeds that of didanosine and is enhanced by administration of the 6
      halogenated prodrugs, although the mechanism of this enhanced penetration is
      unclear.

PMID- 7574513
TI  - Susceptibility of Encephalitozoon cuniculi to several drugs in vitro.
AB  - In the light of the increased incidence of human Encephalitozoon infections and
      the absence of an established treatment protocol, a simple in vitro testing
      method to compare activities of drugs against Encephalitozoon cuniculi was
      developed. With this in vitro method, the 50% inhibitory concentrations of
      fumagillin, thiabendazole, albendazole, oxibendazole, and propamidine isethionate
      for E. cuniculi in rabbit kidney cells were determined. Itraconazole,
      toltrazuril, metronidazole, ronidazole, and ganciclovir were ineffective in this
      testing system.

PMID- 7574514
TI  - Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium
      tuberculosis: investigations into mechanism of action of and mechanism of
      resistance to pyrazinamide.
AB  - The mechanism of action of pyrazinamide (PZA) is not known. One hypothesis is
      that PZA functions as a prodrug of pyrazinoic acid. Susceptibility to PZA
      correlates with amidase activity of the Mycobacterium tuberculosis isolate in
      question. PZA-resistant isolates retain susceptibility in vitro to pyrazinoic
      acid and n-propyl pyrazinoate. Esters of pyrazinoic acid appear to circumvent the
      requirement for activation by mycobacterial amidase. The MICs of n-propyl
      pyrazinoate for M. tuberculosis isolates are lower than those of pyrazinoic acid.
      Further studies to assess the effects of modifications of the alcohol and
      pyrazine moieties of pyrazinoate esters on in vitro and in vivo antituberculosis
      activity are under way. This may lead to a candidate compound with enhanced
      activity against both PZA-susceptible and PZA-resistant M. tuberculosis isolates
      suitable for clinical development.

PMID- 7574515
TI  - Characterization of a conjugative staphylococcal mupirocin resistance plasmid.
AB  - We studied conjugative plasmids encoding high-level mupirocin resistance. These
      plasmids were found in Staphylococcus aureus isolates from two geographic
      locations in the United States. Transfer genes on three mupirocin resistance
      plasmids with different restriction endonuclease profiles were indistinguishable
      by DNA hybridization from those on pG01, a conjugative aminoglycoside resistance
      plasmid representative of similar plasmids that are prevalent in the United
      States. One mupirocin resistance plasmid, pG0400 (34 kb), was smaller than pG01
      (52 kb) because of the absence from pG0400 of DNA, found on pG01, that contained
      genes encoding resistance to aminoglycosides, trimethoprim, and quaternary
      ammonium compounds flanked by directly repeated copies of the insertion sequence
      (IS)-like element IS431-IS257. The plasmids pG0400 and pG01 were otherwise
      indistinguishable except for the presence in pG0400 of a 4.5-kb HinDIII fragment
      encoding mupirocin resistance. The added mupirocin resistance gene was flanked by
      two directly repeated copies of IS431/257. The nucleotide sequence of DNA
      contiguous to the outside of the IS elements, as well as those of the elements
      themselves, was identical in both pG01 and pG0400, and there were no target site
      duplications flanking either copy of the element. We conclude that the mupirocin
      resistance gene was added to an existing conjugative plasmid in conjunction with
      the deletion of other resistance genes by recombination at IS elements. The
      construction of conjugative plasmids carrying a mupirocin resistance gene may be
      a model for the mobility of other resistance genes newly acquired by
      staphylococci.

PMID- 7574516
TI  - Effects of ciprofloxacin and protamine sulfate combinations against catheter
      associated Pseudomonas aeruginosa biofilms.
AB  - Infection is a common complication associated with the use of transcutaneous and
      implanted medical devices. These infections are generally difficult to treat and
      frequently require removal of the biomaterial before the infection can be
      completely eradicated. The presence of a bacterial biofilm recalcitrant to
      treatment often mediates these infections. We studied the influence of a
      polycationic protein, protamine sulfate, on the efficacy of the fluoroquinolone
      ciprofloxacin against a clinical isolate of Pseudomonas aeruginosa. A P.
      aeruginosa biofilm was developed on 1-cm sections of red rubber catheter material
      and then treated with various combinations of protamine sulfate and
      ciprofloxacin. The present work demonstrated that ciprofloxacin in combination
      with protamine was more effective against biofilms than was ciprofloxacin alone.
      Protamine sulfate at 50 micrograms/ml combined with antibiotic at 0.5
      microgram/ml reduced the number of viable cells by an average of 98.97%, while
      protamine sulfate at 50 micrograms/ml alone resulted in an average 107.8%
      increase and antibiotic alone resulted in an average 58.6% reduction after 24 h.
      Furthermore, protamine sulfate, in combination with ciprofloxacin, inhibited P.
      aeruginosa in a dose-dependent fashion. It was further observed that treatment
      with the combination of protamine sulfate and ciprofloxacin had a more drastic
      effect on planktonic organisms as compared with the P. aeruginosa biofilms; the
      MBC was reduced to < 0.05 microgram/ml in the presence of 25 micrograms of
      protamine sulfate per ml. These findings were substantiated by ultrastructure
      studies of treated cells using scanning and transmission electron microscopy. The
      synergism between ciprofloxacin and protamine sulfate significantly enhanced the
      efficacy of ciprofloxacin against planktonic and biofilm P. aeruginosa.

PMID- 7574517
TI  - Antiviral susceptibility testing with a cell line which expresses beta
      galactosidase after infection with herpes simplex virus.
AB  - Despite increasing concern about drug-resistant herpes simplex virus (HSV),
      antiviral susceptibility testing is not routinely performed by most clinical
      virology laboratories. This omission is in large part because the most widely
      accepted method, the plaque reduction assay (PRA), is cumbersome to perform and
      results are rarely available in time to influence treatment. We report here the
      development of a sensitivity test for HSV which utilizes a cell line
      (VeroICP6LacZ#7) that expresses beta-galactosidase activity after infection with
      HSV such that infected cells can be detected by histochemical staining. We
      designed an assay in which 10-fold dilutions of virus stocks with undetermined
      titers were inoculated onto VeroICP6LacZ#7 cells in a 24-well tissue culture
      dish. Forty-eight hours after infection, the cell monolayers were histochemically
      stained. Plaques appear blue against a clear background and are thus easily
      visualized at 48 h. As with the standard PRA, the 50% inhibitory concentration
      (IC50) was reported as the concentration of an antiviral drug that reduces the
      number of plaques by 50%. Evaluation of 10 well-characterized laboratory strains
      and 12 clinical HSV isolates showed that the IC50 determined by this method
      correlated in all instances with the IC50 determined by the PRA. This method is
      easy to use and eliminates the need to determine the titer of the virus, and
      results are available within 48 h of the detection of the virus. VeroICP6Lac#7
      cells are a useful tool for performing HSV antiviral susceptibility testing and
      could be used in a number of different formats to facilitate the identification
      of drug-resistant isolates of HSV.

PMID- 7574518
TI  - Evaluation of antibiotic therapies for eradication of Helicobacter hepaticus.
AB  - The newly recognized murine pathogen Helicobacter hepaticus is known to colonize
      the ceca and colons of several strains of mice from a variety of commercial
      suppliers. Additionally, the organism persistently infects mice, causes a chronic
      hepatitis, and is linked to hepatic tumors in the A/JCr inbred mouse strain. For
      this reason, eradication of the organism from infected mouse colonies is
      desirable. Treatment modalities for eradication of H. hepaticus from the
      gastrointestinal system consisted of oral administration of various antibiotic
      combinations previously evaluated for eradication of experimental H. felis
      gastric infection in mice. A/JCr mice (8 to 10 weeks old) naturally infected with
      H. hepaticus were divided into six treatment groups of 10 animals each. Animals
      received monotherapy of amoxicillin, metronidazole, or tetracycline or triple
      therapy of amoxicillin-metronidazole-bismuth (AMB) or tetracycline-metronidazole
      bismuth (TMB). All medications were administered by oral gavage three times daily
      for 2 weeks. One month after the final treatment, mice were euthanatized and
      livers, ceca, and colons were cultured for H. hepaticus. All untreated control
      animals had H. hepaticus isolated from the cecum and/or colon. H. hepaticus was
      not recovered from the livers, ceca, or colons of the AMB or TMB treatment
      groups. All animals receiving the various antibiotic monotherapies had H.
      hepaticus isolated from the cecum and colon. We conclude that at the doses and
      the route evaluated, AMB and TMB triple therapies are effective for eradication
      of H. hepaticus in 8- to 10-week old A/JCr mice.

PMID- 7574519
TI  - Bacterial activity of a new antiulcer agent, ecabet sodium, against Helicobacter
      pylori under acidic conditions.
AB  - Helicobacter pylori NCTC 11637, which is nonviable at pH 3.0, became viable after
      addition of 10 mM urea owing to ammonia production by urease. In a buffer
      supplemented with urea, ecabet sodium decreased both the production of ammonia
      and the number of viable cells of H. pylori NCTC 11637 and changed the bacteria
      from the bacilliform to the horseshoe or doughnut shape in a concentration
      dependent manner. In particular, ecabet sodium (2 and 4 mg/ml) decreased the
      number of viable cells below the control level. Benzohydroxamic acid, a urease
      inhibitor, also caused a decrease in ammonia production accompanied by a decrease
      in the number of viable cells and changed the morphological form at pH 3.0, but
      the number of viable cells was not lowered below the control level. In buffers at
      various pHs without urea, ecabet sodium showed a concentration-dependent
      bactericidal effect on H. pylori at pHs 4.0 and 5.0 but not at pHs 6.0 and 7.0
      while benzohydroxamic acid caused only a slight decrease in the number of viable
      cells at pH 4.0. These results suggest that ecabet sodium has strong bactericidal
      activity in addition to its urease-inhibiting activity under acidic conditions.

PMID- 7574520
TI  - Interactions of biapenem with active-site serine and metallo-beta-lactamases.
AB  - Biapenem, formerly LJC 10,627 or L-627, a carbapenem antibiotic, was studied in
      its interactions with 12 beta-lactamases belonging to the four molecular classes
      proposed by R. P. Ambler (Philos. Trans. R. Soc. Lond. Biol. Sci. 289:321-331,
      1980). Kinetic parameters were determined. Biapenem was readily inactivated by
      metallo-beta-lactamases but behaved as a transient inhibitor of the active-site
      serine enzymes tested, although with different acylation efficiency values. Class
      A and class D beta-lactamases were unable to confer in vitro resistance toward
      this carbapenem antibiotic. Surprisingly, the same situation was found in the
      case of class B enzymes from Aeromonas hydrophila AE036 and Bacillus cereus 5/B/6
      when expressed in Escherichia coli strains.

PMID- 7574521
TI  - Genetic analysis of clinical isolates of Streptococcus pneumoniae with high-level
      resistance to expanded-spectrum cephalosporins.
AB  - Streptococcus pneumoniae CS109 and CS111 were isolated in the United States in
      1991 and have high levels of resistance to expanded-spectrum cephalosporins (MICs
      of 8 and 32 micrograms of cefotaxime per ml, respectively). CS109, but not CS111,
      also showed high-level resistance to penicillin. As both strains expressed the
      serotype 23F capsule, were very closely related in overall genotype, and
      possessed identical or closely related mosaic pbp1a, pbp2x, and pbp2b genes, it
      is likely that they have arisen from a recent common ancestor. High-level
      resistance to expanded-spectrum cephalosporins was entirely due to alterations of
      penicillin-binding proteins (PBPs) 1a and 2x, since a mixture of the cloned pbp1a
      and pbp2x genes from the resistant strains could transform the susceptible strain
      R6 to the full level of cephalosporin resistance of the clinical isolates. Both
      PBP1a and PBP2x of these strains were more resistant to inhibition by
      cephalosporins than those of typical highly penicillin-resistant isolates. The
      pbp1a genes of CS109 and CS111 were identical in sequence, and the fourfold
      difference in their levels of resistance to cephalosporins was due to a Thr-550-
      >Ala substitution at the residue following the conserved Lys-Ser-Gly motif of
      PBP2x. This substitution was also the major cause of the 16-fold-lower resistance
      of CS111 to penicillin. The pbp2x gene of CS111, in an appropriate genetic
      background, could provide resistance to 16 micrograms of cefotaxime per ml but
      only to 0.12 microgram of benzylpenicillin per ml. Removal of the codon 550
      mutation resulted in a pbp2x gene that provided resistance to 4 microgram of
      cefotaxime per ml and 4 microgram of benzylpenicillin per ml. The Thr-550-->Ala
      substitution in CS111 therefore appears to provide increased resistance to
      expanded-spectrum cephalosporins but a loss of resistance to penicillin.

PMID- 7574522
TI  - Different patterns of bacterial DNA synthesis during postantibiotic effect.
AB  - Studies on bacterial metabolism during the postantibiotic effect (PAE) period are
      limited but might provide insight into the nature of the PAE. We evaluated the
      rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of
      organisms in the logarithmic growth phase to various antibiotics. Staphylococcus
      aureus ATCC 25923 was exposed to vancomycin, dicloxacillin, rifampin, and
      ciprofloxacin; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin,
      rifampin, imipenem, and ciprofloxacin; and Pseudomonas aeruginosa ATCC 25783 was
      exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined
      by measuring the rate of [3H]thymidine incorporation in S. aureus and E. coli and
      [3H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was
      suppressed during the PAE phase with vancomycin, dicloxacillin, and rifampin, it
      was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa
      after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced
      in the gram-negative bacilli after exposure to imipenem and in all three species
      after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only
      minimally affected after exposure to tobramycin and gentamicin. The differences
      in DNA synthesis observed after exposure to various antimicrobial agents suggest
      multiple mechanisms for the PAE.

PMID- 7574523
TI  - New semisynthetic pneumocandins with improved efficacies against Pneumocystis
      carinii in the rat.
AB  - A new series of semisynthetic, water-soluble pneumocandin analogs has been found
      to be extremely potent against Pneumocystis carinii in an immunocompromised-rat
      model. These compounds are 5 to 10 times more potent than the parent natural
      product, pneumocandin B0 (L-688,786) (R. E. Schwartz et al., J. Antibiot. 45:1853
      1866, 1992), and > 100 times more potent than cilofungin. One compound in
      particular, L-733,560, had a 90% effective dose against P. carinii cysts of 0.01
      mg/kg of body weight when delivered parenterally (subcutaneously, twice daily for
      4 days). This compound was also effective when given orally for the treatment and
      prevention of P. carinii pneumonia. For treating acute P. carinii pneumonia, oral
      doses of 2.2 mg/kg twice daily for 4 days were required to eliminate 90% of the
      cysts. A once-daily oral prophylactic dose of 2.2 mg/kg prevented cyst
      development, and a dose of 6.2 mg/kg prevented any development of P. carinii
      organisms (cysts and trophozoites), as determined through the use of a P. carinii
      specific DNA probe (P. A. Liberator et al., J. Clin. Microbiol. 30:2968-2974,
      1992). These results demonstrate that the antipneumocystis activities of the
      pneumocandins can be significantly improved through synthetic modification.
      Several of these compounds are also extremely effective against candidiasis (K.
      Bartizal et al., Antimicrob. Agents Chemother. 39:1070-1076, 1995) and
      aspergillosis (G. K. Abruzzo et al., Antimicrob. Agents Chemother. 39:860-894,
      1995) in murine models, making them attractive as broad-spectrum antifungal
      agents.

PMID- 7574524
TI  - Noncytotoxic combinations of topical antimicrobial agents for use with cultured
      skin substitutes.
AB  - Cultured skin grafts are destroyed more easily than split-thickness skin grafts
      by common burn wound organisms, including gram-negative and gram-positive
      bacteria and fungi. To increase the survival and engraftment of cultured skin
      grafts, formulations of antimicrobial agents were tested for cytotoxicity to
      cultured human keratinocytes and fibroblasts and for activity against common
      organisms from burn wounds. On the basis of previous studies, a base formulation
      containing neomycin (40 micrograms/ml), polymyxin B (700 U/ml), and mupirocin (40
      micrograms/ml) was prepared, to which ciprofloxacin (20 micrograms/ml) or
      norfloxacin (20 micrograms/ml) and amphotericin B (0.25 microgram/ml) or nystatin
      (100 U/ml) were added. Toxicity to cultured human cells was determined by the
      growth response of cell cultures (n = 6) to each drug combination over 4 days.
      Activity against clinical isolates (n = 40) of Staphylococcus aureus, Pseudomonas
      aeruginosa, other gram-negative bacteria, and Candida spp. was determined by the
      wet disc assay. Analysis of variance testing showed no significant differences in
      the growth of keratinocytes or fibroblasts under control or experimental
      conditions. Medium without antimicrobial agents was not effective against any of
      the 40 microbial strains tested. The base formulation was effective against all
      bacterial strains tested but against none of the fungi, while all experimental
      formulations were effective against all microbial strains tested. These findings
      suggest that neomycin, mupirocin, and polymyxin B may be combined with a
      quinolone and an antimycotic agent to provide broad antimicrobial activity for a
      formulation for topical use with cultured skin on burns. However, the
      formulations described here are strictly experimental and are not recommended for
      clinical use without further evaluation.

PMID- 7574525
TI  - The PETT series, a new class of potent nonnucleoside inhibitors of human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - To identify the minimal structural elements necessary for biological activity,
      the rigid tricyclic nucleus of the known human immunodeficiency virus type 1 (HIV
      1) reverse transcriptase (RT) inhibitor tetrahydroimidazobenzodiazepinthione was
      subjected to systematic bond disconnection to obtain simpler structures. A
      rational selection and testing of modeled analogs containing these potential
      pharmacophoric moieties led to the discovery of a new series of nonnucleoside
      inhibitors of RT. The lead compound of this new PETT series of nonnucleoside RT
      inhibitors, N-(2-phenylethyl)-N'-(2-thiazolyl)thiourea (LY73497), was found to
      inhibit HIV-1 but not HIV-2 or simian immunodeficiency virus in cell culture at
      micromolar concentrations. This derivative was also found to inhibit HIV-1 RT.
      Through an integrated effort involving synthesis and molecular modeling,
      compounds with nanomolar potency against HIV-1 in cell culture were developed. In
      these studies, LY300046-HCl was identified as a potent nonnucleoside inhibitor of
      HIV-1 RT possessing favorable pharmacokinetic properties.

PMID- 7574526
TI  - Interleukin 10 reduces mortality from severe peritonitis in mice.
AB  - Interleukin 10 (IL-10) is known to suppress the induction of proinflammatory
      cytokines such as tumor necrosis factor (TNF) and IL-1 and is itself induced by
      monocytes and macrophages during sepsis. We studied the therapeutic efficacy of
      IL-10 by testing its effect on the survival rate in the murine cecal ligation-and
      puncture (CLP) model. Administration of 1 microgram or more of recombinant murine
      IL-10 6 h after induction of sepsis decreased lethality in septic mice
      significantly and also suppressed the elevation of circulating TNF after sepsis.
      However, treatment with the same dose of IL-10 simultaneously or 6 h before
      induction of CLP had no effect on survival, and treatment with anti-TNF antibody
      after induction of CLP had no effect on the survival rate. These data suggest
      that cytokine modulation with IL-10 is a potential candidate for the treatment of
      sepsis and sepsis-related multiple organ failure.

PMID- 7574528
TI  - Evaluation of SCH51048 in an experimental model of pulmonary aspergillosis.
AB  - The efficacy of a novel triazole, SCH51048, was assessed with a murine model of
      pulmonary aspergillosis and was compared with those of SCH39304 and itraconazole.
      A wide range of doses of SCH51048 (5 to 50 mg/kg of body weight) was evaluated.
      Mortality was significantly delayed in mice treated with doses of 5 mg of
      SCH51048 per kg or greater in comparison with mortality in controls (P < 0.05).
      Both SCH51048 and SCH39304 at higher doses (30 and 50 mg/kg) reduced the number
      of viable Aspergillus fumigatus organisms in lung tissue (P < 0.05). In the
      present model, itraconazole neither delayed mortality nor significantly reduced
      the counts in tissue at the doses used. We conclude that SCH51048 is an effective
      therapy for murine pulmonary aspergillosis.

PMID- 7574527
TI  - In vitro and in vivo activities of levofloxacin against Mycobacterium
      tuberculosis.
AB  - In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC
      at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution
      less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but
      the MICs at which 90% of the strains are inhibited were similar. The in vivo
      activity of LVFX against M. tuberculosis was compared with the activities of
      isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with
      1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out
      six times weekly for 4 weeks. The severity of infection and effectiveness of
      treatment were assessed by survival rate, spleen weights, gross lung lesions, and
      enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti
      M. tuberculosis activities of the treatments used ran in the following order:
      LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg)
      > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It
      seems, therefore, that the in vivo activity of LVFX is comparable to that
      produced by a twofold-greater dosage of OFLO. It is assumed that the maximal
      clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg
      daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX
      displayed powerful bactericidal activity, promising effects against human
      tuberculosis may be achieved if patients are treated with the maximal clinically
      tolerated dosage of LVFX.

PMID- 7574529
TI  - Activities of poloxamer CRL8131 against Mycobacterium tuberculosis in vitro and
      in vivo.
AB  - A poloxamer surfactant, CRL8131, was evaluated for activity against Mycobacterium
      tuberculosis (Erdman) by itself and in combination with antibiotics in broth
      culture, in a macrophage cell line assay, and in testing with mice. In the broth
      culture, CRL8131 suppressed the growth of M. tuberculosis and produced
      synergistic effects in combination with isoniazid, rifampin, and streptomycin. It
      also displayed synergy with isoniazid and rifampin against two drug-resistant
      isolates. In the macrophage cell line assay, CRL8131 produced a synergistic
      effect on intracellular killing of M. tuberculosis by isoniazid, rifampin,
      streptomycin, pyrazinamide, thiacetazone, D-cycloserine, ethionamide, amikacin,
      clindamycin, and p-aminosalicylic acid. It demonstrated no synergy or antagonism
      with ethambutol, gentamicin, kanamycin, ciprofloxacin, or nalidixic acid.
      Finally, with C57BL/6 mice infected with M. tuberculosis, a combination of
      CRL8131 and either thiacetazone or pyrazinamide produced 100% survival at 40 days
      whereas the antibiotics produced only 33% survival and CRL8131 produced 0%
      survival when used as single agents. This improved survival rate was associated
      with a significant reduction in the number of organisms in the lungs and spleens
      of infected mice.

PMID- 7574530
TI  - Pharmacokinetics of clarithromycin and zidovudine in patients with AIDS.
AB  - The interrelationships between the pharmacokinetics of zidovudine alone and of
      zidovudine plus clarithromycin were evaluated with 18 volunteers with AIDS who
      had no infection with Mycobacterium avium complex or clinical evidence of
      gastroenteritis. Patients received 200 mg of zidovudine orally every 8 h on days
      1 to 4 and 1,000 mg of clarithromycin every 12 h, given 2 h apart from
      zidovudine, on days 2 to 4. Concentrations of zidovudine in plasma were measured
      at steady state both prior to (phase 1, day 1) and during (phase 2, day 4)
      administration of clarithromycin. Levels of clarithromycin were measured at
      steady state on day 4. The maximum concentrations of zidovudine in plasma were
      significantly different in phases 1 and 2 (616.6 and 949.0 ng/ml, respectively),
      as were the times to the maximum concentrations of zidovudine (2.1 and 1.0 h,
      respectively). However, the minimum concentrations in plasma and the areas under
      the concentration-time curves from 0 to 6 h did not differ on days 1 and 4. There
      is no significant impact on the overall bioavailability of zidovudine from the
      addition of clarithromycin in patients with AIDS. Clarithromycin may increase the
      rate of zidovudine absorption, but this is unlikely to have clinical relevance.

PMID- 7574531
TI  - Activities of amphotericin B and antifungal azoles alone and in combination
      against Pseudallescheria boydii.
AB  - In order to develop new approaches to treatment of infections due to
      Pseudallescheria boydii, the in vitro antifungal activity of amphotericin B alone
      and in combination with miconazole, itraconazole, and fluconazole was studied.
      Combinations of amphotericin B and antifungal azoles were synergistic, additive,
      or indifferent in their interaction against P. boydii. Antagonism was not
      observed.

PMID- 7574532
TI  - Point mutation in the pribnow box, the molecular basis of beta-lactamase
      overproduction in Klebsiella oxytoca.
AB  - Klebsiella oxytoca mutants resistant to a variety of beta-lactams were obtained
      in vitro on aztreonam. Constitutive beta-lactamase production was much higher in
      the mutants than in the susceptible strains (75-fold). The only difference
      observed in these mutants compared with the susceptible strains were point
      mutations in the Pribnow box: a transversion (G-->T) in the first base for one
      mutant or a transition (G-->A) in the fifth base of the -10 consensus sequence
      for the other three mutants. The transcriptional output of the beta-lactamase
      gene (blaOXY) from the mutants was significantly higher than that of the blaOXY
      gene from the susceptible strains.

PMID- 7574533
TI  - Protection of mice from Mycobacterium avium infection by recombinant interleukin
      12.
AB  - Treatment with interleukin-12 (IL-12) significantly reduced the number of viable
      bacteria in mice infected with Mycobacterium avium. IL-12 itself, however, could
      not inhibit directly mycobacterial growth in vitro. IL-12 exerts
      antimycobacterial activity in vivo with a low level of toxicity, possibly by
      enhancing the host defense against the infection.

PMID- 7574534
TI  - Intracellular accumulation of ofloxacin-loaded liposomes in human synovial
      fibroblasts.
AB  - In order to incorporate ofloxacin within liposomes, the reverse-phase evaporation
      technique was carried out. The liposome lipid matrix consisted of
      dipalmitoylphosphatidylcholine-cholesterol-dihexadecylphosphate (4: 3:4 molar
      ratio). The liposome formulation presented a mean size of 185 +/- 31 nm and had
      an encapsulation capacity of 5.3 microliters/mumol. The liposome formulation was
      able to deliver ofloxacin into McCoy cells in a greater amount (2.6-fold) than
      the free drug, improving antibiotic accumulation.

PMID- 7574535
TI  - Drug interactions with zidovudine phosphorylation in vitro.
AB  - We have investigated the effect of a range of drugs (some commonly coadministered
      with zidovudine [ZDV] to human immunodeficiency virus-positive patients) on
      intracellular phosphorylation of ZDV by stimulated peripheral blood mononuclear
      cells, Molt 4 cells, and U937 cells in vitro. Of the drugs tested (azoles,
      antiviral agents, antibiotics, and anticancer agents), only doxorubicin and
      ribavirin caused inhibition of anabolite formation as measured by high
      performance liquid chromatography. This in vitro approach may provide important
      leads to potential interactions at the phosphorylation level in patients with
      human immunodeficiency virus disease. It is reassuring that so many commonly
      administered drugs do not alter ZDV phosphorylation.

PMID- 7574536
TI  - Molecular characterization of the OXA-7 beta-lactamase gene.
AB  - The OXA-7 gene, which encodes an oxacillinase, was cloned from plasmid pMG202 of
      Escherichia coli isolate 7181 (A. A. Medeiros, M. Cohenford, and G. A. Jacoby,
      Antimicrob. Agents Chemother. 27:715-719, 1985) and sequenced. The nucleotide
      sequence of the OXA-7 gene was closely related to that of the OXA-10 (PSE-2)
      gene, with a derived amino acid sequence of the OXA-7 enzyme showing greater than
      95% homology with those of OXA-10 and OXA-11.

PMID- 7574537
TI  - Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics, and
      intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol.
AB  - Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is
      active against ACV-resistant strains of herpes simplex virus because of its
      intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)
      infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal
      [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1
      mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory
      concentration for 18 days. Intravitreal ganciclovir persists above its 90%
      inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local
      treatment for HCMV retinitis.

PMID- 7574538
TI  - In vitro antibiotic susceptibility testing of clinical isolates of Mycoplasma
      penetrans from patients with AIDS.
AB  - In vitro susceptibilities of Mycoplasma penetrans were determined. MICs and MBCs
      were determined. The MICs at which 50% of the isolates are inhibited (micrograms
      per milliliter) for broth dilution testing were as follows: azithromycin, 0.039;
      chloramphenicol, 0.625; ciprofloxacin, 0.156; clindamycin, 0.078; doxycycline,
      0.312; erythromycin, 0.312; gentamicin. > 10; levofloxacin, 0.078; lincomycin,
      0.625; streptomycin, > 10; and tetracycline, 1.25. Bactericidal activity was
      significant only for ciprofloxacin (MBC at which 50% of the isolates are killed,
      0.312 microgram/ml) and levofloxacin (MBC at which 50% of the isolates are
      killed, 0.312 microgram/ml).

PMID- 7574539
TI  - Carryover of clofazimine into culture media.

PMID- 7574540
TI  - Antiviral resistance--an emerging problem.

PMID- 7574541
TI  - Molecular mechanisms of antiviral resistance.

PMID- 7574542
TI  - Assays for antiviral drug resistance.

PMID- 7574544
TI  - Antiviral resistance in clinical practice.

PMID- 7574543
TI  - Models of antiviral resistance.

PMID- 7574545
TI  - Research initiatives in studies of antiviral resistance and consensus points and
      recommendations.

PMID- 7574546
TI  - Molecular evolution in bacteria.
AB  - Recent advances in microbiology and molecular biology have a unifying influence
      on our understanding of genetic diversity/similarity and evolutionary
      relationships in microorganisms. This article attempts to unify information from
      diverse areas such as microbiology, molecular biology, microbial physiology, clay
      crystal genes, metals-microbe-clay interactions and bacterial DNA restriction
      modification systems (R-M) as they may apply to molecular evolution of bacteria.
      The possibility is discussed that the first informational molecules may have been
      catalytic RNA (micro-assembler) not DNA (now the master copy) and these first
      micro-assemblers may have been precursors of ribosomes.

PMID- 7574547
TI  - The fine structure of ascospore shape and development in Ceratocystis fimbriata.
AB  - Ascospore development in Ceratocystis fimbriata Ell. & Halst. commenced in an
      eight-nucleate ascus. A single vesicle formed along the periphery of the ascus
      from fragments of ascospore delimiting membranes, surrounded all eight nuclei and
      eventually invaginated, first forming pouches with open ends, then finally
      enclosing each of the eight nuclei in a separate sac, thus delimiting ascospores.
      Pairing of the ascospores followed and brim formation occurred at the contact
      area between two ascospores. Osmiophilic bodies contributed to the formation of
      brim-like appendages by fusing to the ascospore walls. Additional brims were
      observed at opposite ends of the ascospores giving them a double-brimmed
      appearance.

PMID- 7574548
TI  - Inorganic-ion resistance by bacteria isolated from a Mexico City freeway.
AB  - Bacteria were isolated from soil samples, containing high exchangeable lead
      concentrations, obtained from a busy freeway in the Mexico City metropolitan
      area. Forty-five selected strains (86.7% Gram-positive) had a single MIC
      distribution pattern for lead (800-1600 micrograms/ml lead nitrate) and were
      considered lead-resistant. The isolates showed variable levels of resistance to
      arsenate (86.7%), chromate (66.7%), cadmium (57.6%), and mercury (31.1%) ions.
      Multiple inorganic-ion resistance was shown by all strains.

PMID- 7574549
TI  - Thermophilic actinomycetes in cane sugar mills: an aeromicrobiologic and
      seroepidemiologic study.
AB  - Aerial prevalence of clinically important thermophilic actinomycetes and
      occurrence of precipitating antibodies against them in sera of 153 exposed
      workers have been reported. The study was carried out in two cane sugar mills
      namely, the Upper Doab Sugar Mills and the Ramala Sugar Mills, located in north
      west India. In both the sugar mills, T. sacchari was the predominant species, it
      accounted for 55.1% and 50.3% of the total population of thermophilic
      actinomycetes, followed by T. vulgaris (19.7% and 23.7%), T. thalpophilus (21.1%
      and 17.1%), Saccharomonospora viridis (3.4% and 5.0%) and Saccharopolyspora
      rectivirgula (Faenia rectivirgula) (0.7% and 3.9%), respectively. Precipitating
      antibodies against thermophilic actinomycetes were demonstrable in 34 (22.2%)
      workers; T. sacchari alone accounted for 20 of the positive precipitin reactions,
      followed by S. rectivirgula in 10. The mean absorbance values for IgG antibody
      activity against T. sacchari as well as S. rectivirgula were found to be elevated
      significantly in the symptomatic workers than in the asymptomatic workers (p <
      0.05) or unexposed controls (p < 0.001). However, the difference in IgG antibody
      activity was insignificant between precipitin-positive symptomatic workers and
      precipitin-positive asymptomatic workers. The results indicate that clinically
      important thermophilic actinomycetes are widely prevalent in cane sugar mills,
      and T. sacchari and S. rectivirgula are the major species involved in the
      sensitization of the bagasse workers in India.

PMID- 7574550
TI  - Localization of the enzymes involved in H2 and formate metabolism in
      Syntrophospora bryantii.
AB  - Cell-free extracts of crotonate-grown cells of the syntrophic butyrate-oxidizing
      bacterium Syntrophospora bryantii contained high hydrogenase activities (8.5-75.8
      mumol.min-1mg-1 protein) and relatively low formate dehydrogenase activities
      (0.04-0.07 mumol.min-1 mg-1 protein). The KM value and threshold value of the
      hydrogenase for H2 were 0.21 mM and 18 microM, respectively, whereas the KM value
      and threshold value of the formate dehydrogenase for formate were 0.22 mM and 10
      microM, respectively. Hydrogenase, butyryl-CoA dehydrogenase and 3-OH-butyryl-CoA
      dehydrogenase were detected in the cytoplasmic fraction. Formate dehydrogenase
      and CO2 reductase were membrane-bound, likely located at the outer aspect of the
      cytoplasmic membrane. Results suggest that during syntrophic butyrate oxidation
      H2 is formed intracellularly while formate is formed at the outside of the cell.

PMID- 7574551
TI  - A new genetically isolated population of the Saccharomyces sensu stricto complex
      from Brazil.
AB  - Genetic and karyotypic studies of some Saccharomyces sensu stricto yeasts from
      Brazil revealed a genetically isolated population which apparently represents a
      new sibling species of S. cerevisiae.

PMID- 7574552
TI  - Enzymatic properties of lipase and characteristics production by Lactobacillus
      delbrueckii subsp. bulgaricus.
AB  - Some properties of an extracellular lipase produced by Lactobacillus delbrueckii
      subsp. bulgaricus were studied. Maximum enzyme activity was found against olive
      and butter oil as enzyme substrates. Addition of 9% acacia gum, 0.1% Na
      deoxycholate and 0.01 M CaCl2 to the enzyme reaction mixture increased-lipase
      activity from 5.3 to 14.5 (FFA/mg protein/minute) at pH 6.0 and at 40 degrees C.
      Maximum lipase production was reached in the presence of glucose as a sole source
      of carbon, wheat bran as nitrogen source, olive oil as a sole lipid source and
      butyric acid as fatty acid supporting the growth medium. An initial pH value of
      the culture medium of 6.0 and a temperature of 35 degrees C gave the highest
      lipolytic activity.

PMID- 7574553
TI  - Saccharomyces species assignment by long range ribotyping.
AB  - Type strains of 10 genotypically distinct Saccharomyces species are
      differentiated by ribosomal DNA restriction fragment analysis (ribotyping). The
      full length of the chromosomal ribosomal repeat was amplified in two parts, the
      18SrDNA including both ITS region (2600 bp) and the 25SrDNA (3300 bp).
      Restriction fragments generated by 9 enzymes from these two products yield
      characteristic patterns, by which unknown Saccharomyces isolates are assigned to
      the type strains. For convenient separation and detection only fragments longer
      than 200 bp were monitored. In contrast to molecular differentiation methods of
      highest resolution as RAPD-PCR or fingerprinting, the results from ribotyping are
      absolutely reproducible and thereby suitable for databases. The phylogeny
      computed from the discrete character matrix for presence/absence of fragments by
      the PHYLIP program package is in complete accordance to the phylogeny derived
      from ribosomal RNA sequence analysis. By this the field of application of the
      long range ribotyping can be regarded basically as equal to DNA sequence analysis
      of the same locus. Because distant relationships are recognized, misidentified
      genera were detected upon the species assignment. This cannot be done by methods
      of higher resolution like RAPD-PCR or fingerprinting.

PMID- 7574554
TI  - Assessment of survival during starvation of Escherichia coli and Klebsiella
      pneumoniae in artificial urine: analysis of the kinetics of colony formation.
AB  - A kinetic model of colony formation was proposed by Hattori, based on a count of
      the colonies that appear on a plate in successive short intervals of time. In
      this model, three parameters (lambda, tr and N infinity) are defined, which
      reflect the ability of a bacterium to yield colonies and allow us to described
      the dynamics of bacterial populations in soil and of E. coli at different growth
      phases. In this paper we report a reparametrization of the kinetic model of
      colony formation, with the aim of facilitating more accurate calculation of
      lambda and tr. Moreover, we observed that during the starvation of E. coli and K.
      pneumoniae in urine, lambda can be used to assess survival, since this parameter
      clearly decreases during starvation. Retardation time values (tr) were similar in
      E. coli and K. pneumoniae throughout the starvation experimental period.

PMID- 7574555
TI  - Analysis of flagellin gene expression in flagellar phase variants of
      Campylobacter jejuni 81116.
AB  - Flagella production in Campylobacter jejuni 81116 is subject to phase variation;
      the bacterium is able to switch its flagellum synthesis, and thereby its
      motility, on and off. Under standard laboratory growth conditions flagellar phase
      variants can be maintained as stable, pure cultures. We found conditions that
      efficiently induced a phase shift in vitro. The flaA gene but not the flaB gene
      is subject to the on and off switch. Minor amounts of FlaB are still present in
      aflagellate cells. We previously showed that flagellin gene expression in phase
      variants was regulated at the transcriptional level. Here, sequence data prove
      that abolishment of flaA transcription is not caused by DNA rearrangements or
      mutations within the flagellin locus. Since flaA is preceded by a typical sigma
      28 promoter a C. jejuni sigma 28 homolog could play a role in regulation of flaA
      gene expression but such a gene or protein could not be detected. However, in
      vitro transcription could be detected using sigma 28-holoenzyme preparations from
      Bacillus subtilis. Possible regulatory mechanisms that may control flagellar
      phase variation in Campylobacter are discussed.

PMID- 7574556
TI  - Cellulose degradation by Leucocoprinus gongylophorus, the fungus cultured by the
      leaf-cutting ant Atta sexdens rubropilosa.
AB  - Leucocoprinus gongylophorus, the fungus cultured by the leaf-cutting ant Atta
      sexdens rubropilosa, is able to degrade efficiently cellulose, microcrystaline
      cellulose, carboximethylcellulose, and cellobiose. Analysis of the degradation
      products indicate that the fungus produce extracellular beta-glucosidase, exo-
      and endo-glucanase. The importance of cellulose degradation to the association of
      fungus and ant is discussed.

PMID- 7574557
TI  - Helpful information for new clinical nurse educators.

PMID- 7574558
TI  - Nurses and physicians attempt to define collaboration and practice roles.

PMID- 7574559
TI  - Substance abuse in the perioperative setting.
AB  - Published information and extensive anecdotal reports from perioperative nurses
      reveal an alarming amount of substance abuse in the perioperative setting. In
      addition to the familiar controlled substances (eg, narcotics, tranquilizers),
      practitioners must be familiar with the potential abuse of anesthesia induction
      agents such as ketamine, nitrous oxide, and general inhalation anesthetics.
      Perioperative nurses need to be aware of the problem of substance abuse in the
      perioperative setting, increase their knowledge of substance abuse practices, be
      alert to signs and symptoms of chemical dependency, and have plans for responding
      to reported substance abuse situations when on duty.

PMID- 7574560
TI  - Educational research.

PMID- 7574561
TI  - Residual organic debris on processed surgical instruments.
AB  - This preliminary study describes the degree of cleanliness of three categories of
      surgical instruments after processing (ie, decontamination, inspection,
      sterilization). The three categories were reusable laparoscopic, reused
      disposable laparoscopic, and conventional surgical instruments. The objective of
      the study was to identify from visual inspection and microscopic examination
      residual particles, stains, or liquid on processed instruments. The investigators
      studied 32 instruments selected at random from a hospital's supply of processed
      surgical instruments. On visual inspection, 90.6% (29/32) of the instruments
      appeared clean. Microscopic examination with a photomicrographic system, however,
      revealed residual debris on 84.3% (27/32) of the instruments. The quantity of
      residual debris on both types of laparoscopic instruments (ie, reusable, reused
      disposable) was equivalent. The conventional instruments contained less residual
      debris than the laparoscopic instruments. Sites that contained residual debris
      included junctions between insulating sheaths and activating mechanisms of
      laparoscopic instruments and articulations and grooves of forceps. More research
      is needed to determine the prevalence and clinical significance of these
      findings.

PMID- 7574562
TI  - Cleanability of hybrid laparoscopic instruments.
AB  - An experiment was conducted to determine if hybrid laparoscopic instruments could
      be cleaned effectively before sterilization. A cleaning protocol that used
      materials readily available to perioperative cleaning personnel was established
      and implemented. Test instruments were soiled under pressure with defibrinated
      sheep's blood to simulate an abdominal laparoscopic surgical procedure (ie, by
      creating a pneumoperitoneum). After being cleaned according to the protocol,
      visual and optical inspections of the instruments indicated that all were free of
      visible soil. It was concluded that a hybrid laparoscopic instrument system can
      be cleaned satisfactorily before sterilization.

PMID- 7574563
TI  - Estimating the true costs of disposable and reusable instruments.
AB  - The real issue in the debate about reusable versus disposable surgical
      instruments is the true cost and efficacy of specific instruments. Each device
      needs to be scrutinized on its own merits and analytically compared to other
      instruments. The goal of this case study was not to promote one type of
      instrument over the other but to focus on some of the data elements and complex
      issues involved in determining true costs, cost-effectiveness, and efficacy of
      the reusable and disposable instruments.

PMID- 7574564
TI  - Laparoscopic electrosurgical complications and their prevention.
AB  - Insulation failures, direct coupling, and capacitive coupling around active
      electrodes may cause serious burns and tissue damage to patients undergoing
      laparoscopic procedures. A coordinated team effort between perioperative nurses
      and surgeons can prevent life-threatening complications from laparoscopic
      electrosurgical procedures. Knowledge of the biophysics of electrosurgery, the
      mechanisms of electrosurgery complications, and prevention of patient injuries
      will empower surgical team members to provide quality outcomes for patients
      undergoing laparoscopic procedures.

PMID- 7574565
TI  - Unsubstantiated assumptions about unlicensed assistive personnel obscure the
      challenge of delivering quality patient care.

PMID- 7574566
TI  - Talc poudrage for treatment of pleural effusion in selected patients.
AB  - Recurring pleural effusions are a significant cause of patient morbidity.
      Treatment goals are to relieve distressing symptoms (eg, dyspnea, pain) caused by
      the effusion, to prevent further extracellular fluid accumulation in the pleural
      space, and to restore the patient to a functional pulmonary status. Talc poudrage
      is a therapy that instills iodized talc through a tube thoracostomy to cover
      opposing pleural surfaces with an irritating powder. Talc stimulates adhesion
      formation that obliterates the pleural space. Recent study results indicate that
      intrapleural instillation of iodized talc is an adequate and effective treatment
      for control of neoplastic or benign pleural effusion.

PMID- 7574567
TI  - Outcomes research on one continuing education activity.
AB  - Outcomes evaluation research on continuing education (CE) is virtually unexplored
      in the perioperative and general nursing literature. This outcomes evaluation
      research study explored whether participants changed their practice behaviors
      after participation in a one-day CE activity (eg, used knowledge gained,
      consistently performed new skills, integrated new values into their practices).
      One hundred seventy-one attendees participated. Data analysis revealed that
      behaviors and practices did change as a result of attending the CE activity.
      Participants reported that the organizations, settings, or departments in which
      they were employed and their peers were challenges to their use of CE in
      practice.

PMID- 7574568
TI  - Hunger-induced finickiness in humans.
AB  - Two experiments were conducted to examine the effect of hunger on finickiness in
      humans. Subjects (a total of 157 undergraduate female dieters and non-dieters)
      were food-deprived and then subsequently either given a snack (not-hungry group)
      or left food-deprived (hungry group) before being given ad libitum access to
      either good-tasting or bad-tasting (quinine-adultered) milkshake. Common sense
      predicted that hungry subjects would drink more milkshake than would not-hungry
      subjects, regardless of milkshake palatability. Hungry subjects did in fact drink
      more of the good-tasting milkshake than did not-hungry subjects, but they also
      drank less of the bad-tasting milkshake. We discuss possible reasons why hunger
      might increase rejection of bad-tasting food, as well as the limiting conditions
      of the effect.

PMID- 7574570
TI  - Towards a political economy of anorexia?

PMID- 7574569
TI  - Factors associated with sources of influence/information in reducing red meat by
      elderly subjects.
AB  - A number of studies have found that health beliefs and social influences predict
      changes in dietary intake, including red meat. These studies have not determined
      what kinds of individuals are more likely to change their diets due to the advice
      of physicians, the advice of significant others, or because of mass-media
      exposure. We obtained data from 424 elderly Houstonians regarding whether they
      had attempted to reduce red meat consumption and if so, why. Social network,
      health status, food attitude and demographic variables are used to differentiate
      those who have made physician-induced changes from other sources of
      influence/information for change. Elderly subjects with smaller abdominal girth
      measurements are more likely to make red meat reductions regardless of the source
      of influence/information; those who believe in the efficacy of health foods are
      more likely to give physicians and mass media as sources of influence/information
      for red meat reductions. Men are more likely than women to report red meat
      reductions because of mass media and physician influences. Women who receive a
      greater amount of companionship from their social networks are more likely to
      change because of friends/relatives influences.

PMID- 7574572
TI  - Bombesin-like peptides and satiety.

PMID- 7574571
TI  - Perceived behavioural control, unrealistic optimism and dietary change: an
      exploratory study.
AB  - In the context of five dietary changes conducive to reductions in fat
      consumption, a short questionnaire was constructed to examine the applicability
      of the theory of planned behaviour and to assess the presence of the phenomenon
      of "unrealistic optimism". An extension to the theory of planned behaviour was
      also included, in the form of a "self-identity" measure assessing identification
      with concern about the health consequences of diet. The questionnaire was
      completed by 612 members of the general public at three different locations in
      the U.K. The findings indicate some support for the applicability of the theory
      of planned behaviour, with the measure of "self-identity" producing some
      additional independent effects. Evidence of unrealistic optimism concerning diet
      related health risks was found, with greater optimism being significantly related
      to lower relative consumption estimates of "unhealthy" foods. The findings are
      discussed in the context of implications for health promotion.

PMID- 7574573
TI  - The chicken or the egg: binge eating disorder and dietary restraint.

PMID- 7574574
TI  - Molecular approaches to conditioned taste aversion.

PMID- 7574575
TI  - Social facilitation of food intake in humans.

PMID- 7574576
TI  - Bombesin receptor subtypes: implications in bombesin satiety.

PMID- 7574577
TI  - A workshop of the Scottish Colloquium on Food and Feeding (SCOFF) and the BSA
      sociology of food group research and practice issues in the study of fruit and
      vegetable consumption, food choice and eating habits.

PMID- 7574578
TI  - Detection of Legionella species in reclaimed water and air with the EnviroAmp
      Legionella PCR kit and direct fluorescent antibody staining.
AB  - Reclaimed water is an important resource for areas with inadequate water
      supplies. However, there have been few studies on the variety of microorganisms
      found in this type of water, since typically reclaimed water is examined only for
      the presence of coliform bacteria. Many microorganisms, including the
      legionellae, are known to be more resistant to chlorine than are coliform
      bacteria. Previously, we detected > 10(3) Legionella cells per ml in primary and
      secondary sewage effluents and observed no significant reduction in population
      numbers throughout the treatment process. In this study, we detected Legionella
      spp. in chlorinated effluent by using an EnviroAmp Legionella PCR kit and direct
      fluorescent antibody (DFA) staining. However, we were not able to isolate
      Legionella spp. from either natural or seeded reclaimed water samples. This
      suggests that the Legionella spp. detected by the PCR and DFA methods may be
      injured or viable but nonculturable after exposure to the high residual chlorine
      levels typically found in this type of water source. The numbers of coliform
      bacteria were low (< 2 cells per 100 ml) in most reclaimed water samples and were
      not correlated with the presence or absence of Legionella spp. We also collected
      air samples from above a secondary aeration basin and analyzed them by using the
      PCR, DFA, and plate culture methods. Legionella spp. were detected in the air
      obtained from above the secondary basin with all three methods. We concluded that
      the PCR was superior to the culture and DFA methods for detecting Legionella spp.
      in environmental water samples.

PMID- 7574579
TI  - Cloning and nucleotide sequencing of the membrane-bound L-sorbosone dehydrogenase
      gene of Acetobacter liquefaciens IFO 12258 and its expression in Gluconobacter
      oxydans.
AB  - Cloning and expression of the gene encoding Acetobacter liquefaciens IFO 12258
      membrane-bound L-sorbosone dehydrogenase (SNDH) were studied. A genomic library
      of A. liquefaciens IFO 12258 was constructed with the mobilizable cosmid vector
      pVK102 (mob+) in Escherichia coli S17-1 (Tra+). The library was transferred by
      conjugal mating into Gluconobacter oxydans OX4, a mutant of G. oxydans IFO 3293
      that accumulates L-sorbosone in the presence of L-sorbose. The transconjugants
      were screened for SNDH activity by performing a direct expression assay. One
      clone harboring plasmid p7A6 converted L-sorbosone to 2-keto-L-gulonic acid
      (2KGA) more rapidly than its host did and also converted L-sorbose to 2KGA with
      no accumulation of L-sorbosone. The insert (25 kb) of p7A6 was shortened to a 3.1
      kb fragment, in which one open reading frame (1,347 bp) was found and was shown
      to encode a polypeptide with a molecular weight of 48,222. The SNDH gene was
      introduced into the 2KGA-producing strain G. oxydans IFO 3293 and its
      derivatives, which contained membrane-bound L-sorbose dehydrogenase. The cloned
      SNDH was correctly located in the membrane of the host. The membrane fraction of
      the clone exhibited almost stoichiometric formation of 2KGA from L-sorbosone and
      L-sorbose. Resting cells of the clones produced 2KGA very efficiently from L
      sorbosone and L-sorbose, but not from D-sorbitol; the conversion yield from L
      sorbosone was improved from approximately 25 to 83%, whereas the yield from L
      sorbose was increased from 68 to 81%. Under fermentation conditions, cloning did
      not obviously improve the yield of 2KGA from L-sorbose.

PMID- 7574580
TI  - A meta cleavage pathway for 4-chlorobenzoate, an intermediate in the metabolism
      of 4-chlorobiphenyl by Pseudomonas cepacia P166.
AB  - Bacterial degradation of biphenyl and polychlorinated biphenyls proceeds by a
      well-studied pathway which produces benzoate and 2-hydroxypent-2,4-dienoate (or,
      in the case of polychlorinated biphenyls, the chlorinated derivatives of these
      compounds). Pseudomonas cepacia P166 utilizes 4-chlorobiphenyl for growth and
      produces 4-chlorobenzoate as a central intermediate. In this study we found that
      strain P166 further transforms 4-chlorobenzoate to 4-chlorocatechol, which is
      mineralized by a meta cleavage pathway. Key metabolites which we identified
      include the meta cleavage product (5-chloro-2-hydroxymuconic semialdehyde), 5
      chloro-2-hydroxymuconate, 5-chloro-2-oxopent-4-enoate, 5-chloro-4-hydroxy-2
      oxopentanoate, and chloroacetate. Chloroacetate accumulated transiently, and slow
      but stoichiometric dehalogenation was observed.

PMID- 7574581
TI  - Regulation of hydrogen sulfide liberation in wine-producing Saccharomyces
      cerevisiae strains by assimilable nitrogen.
AB  - Saccharomyces cerevisiae wine-producing yeast cultures grown under model
      winemaking conditions could be induced to liberate hydrogen sulfide (H2S) by
      starvation for assimilable nitrogen. The amount of H2S produced was dependent on
      the yeast strain, the sulfur precursor compound, the culture growth rate, and the
      activity of the sulfite reductase enzyme (EC 1.8.1.2) immediately before nitrogen
      depletion. Increased H2S formation relative to its utilization by metabolism was
      not a consequence of a de novo synthesis of sulfite reductase. The greatest
      amount of H2S was produced when nitrogen became depleted during the exponential
      phase of growth or during growth on amino acids capable of supporting short
      doubling times. Both sulfate and sulfite were able to act as substrates for the
      generation of H2S in the absence of assimilable nitrogen; however, sulfate
      reduction was tightly regulated, leading to limited H2S liberation, whereas
      sulfite reduction appeared to be uncontrolled. In addition to ammonium, most
      amino acids were able to suppress the liberation of excess H2S when added as sole
      sources of nitrogen, particularly for one of the strains studied. Cysteine was
      the most notable exception, inducing the liberation of H2S at levels exceeding
      that of the nitrogen-depleted control. Threonine and proline also proved to be
      poor substitutes for ammonium. These data suggest that any compound that can
      efficiently generate sulfide-binding nitrogenous precursors of organic sulfur
      compounds will prevent the liberation of excess H2S.

PMID- 7574582
TI  - Sequence and molecular characterization of a DNA region encoding the
      dibenzothiophene desulfurization operon of Rhodococcus sp. strain IGTS8.
AB  - Dibenzothiophene (DBT), a model compound for sulfur-containing organic molecules
      found in fossil fuels, can be desulfurized to 2-hydroxybiphenyl (2-HBP) by
      Rhodococcus sp. strain IGTS8. Complementation of a desulfurization (dsz) mutant
      provided the genes from Rhodococcus sp. strain IGTS8 responsible for
      desulfurization. A 6.7-kb TaqI fragment cloned in Escherichia coli-Rhodococcus
      shuttle vector pRR-6 was found to both complement this mutation and confer
      desulfurization to Rhodococcus fascians, which normally is not able to
      desulfurize DBT. Expression of this fragment in E. coli also conferred the
      ability to desulfurize DBT. A molecular analysis of the cloned fragment revealed
      a single operon containing three open reading frames involved in the conversion
      of DBT to 2-HBP. The three genes were designated dszA, dszB, and dszC. Neither
      the nucleotide sequences nor the deduced amino acid sequences of the enzymes
      exhibited significant similarity to sequences obtained from the GenBank, EMBL,
      and Swiss-Prot databases, indicating that these enzymes are novel enzymes.
      Subclone analyses revealed that the gene product of dszC converts DBT directly to
      DBT-sulfone and that the gene products of dszA and dszB act in concert to convert
      DBT-sulfone to 2-HBP.

PMID- 7574583
TI  - Sandwich enzyme-linked immunosorbent assay for Vibrio vulnificus hemolysin to
      detect V. vulnificus in environmental specimens.
AB  - Vibrio vulnificus hemolysin, purified by quantitative isoelectric focusing, was
      used to prepare rabbit and goat anti-hemolysin. The resulting antibodies were
      used as capture and detector antibody reagents in a sandwich enzyme-linked
      immunosorbent assay (ELISA) to detect V. vulnificus in environmental samples. By
      this technique, 4 laboratory-maintained V. vulnificus strains and 33
      environmental V. vulnificus isolates were detected. Also, the technique
      distinguished five other Vibrio species from V. vulnificus, and when it was used
      in combination with colistin-polymyxin-cellobiose agar, 31 non-V. vulnificus
      isolated were excluded. This sandwich ELISA compared favorably with the current
      Food and Drug Administration standard immunoassay in confirming presumptive V.
      vulnificus colonies from environmental specimens: oysters, sediment, and
      seawater. Among 340 presumptive V. vulnificus colonies, the sandwich ELISA
      detected 95% of the confirmed V. vulnificus colonies. Equally important, the
      technique correctly distinguished 99% of the non-V. vulnificus colonies. The
      sandwich ELISA offers time-saving and labor-saving advantages over the currently
      accepted immunoassay.

PMID- 7574584
TI  - A stochastic killing system for biological containment of Escherichia coli.
AB  - Bacteria with a stochastic conditional lethal containment system have been
      constructed. The invertible switch promoter located upstream of the fimA gene
      from Escherichia coli was inserted as expression cassette in front of the lethal
      gef gene deleted of its own natural promoter. The resulting fusion was placed on
      a plasmid and transformed to E. coli. The phenotype connected with the presence
      of such a plasmid was to reduce the population growth rate with increasing
      significance as the cell growth rate was reduced. In very fast growing cells,
      there was no measurable effect on growth rate. When a culture of E. coli
      harboring the plasmid comprising the containment system is left as stationary
      cells in suspension without nutrients, viability drops exponentially over a
      period of several days, in contrast to the control cells, which maintain
      viability nearly unaffected during the same period of time. Similar results were
      obtained with a strain in which the killing cassette was inserted in the
      chromosome. In competition with noncontained cells during growth, the contained
      cells are always outcompeted. Stochastic killing obtained by the fim-gef fusion
      is at present relevant only as a containment approach for E. coli, but the model
      may be mimicked in other organisms by using species-specific stochastic
      expression systems.

PMID- 7574585
TI  - Studies of Streptomyces reticuli cel-1 (cellulase) gene expression in
      Streptomyces strains, Escherichia coli, and Bacillus subtilis.
AB  - Various streptomyces strains [Streptomyces lividans 66, Streptomyces vinaceus,
      and Strepotmyces coelicolor A3 (2)] acquired the ability to utilize crystalline
      cellulose (Avicel) after transformation with a multicopy vector containing the
      cel-1 gene from Streptomyces reticuli. The expression level in these hosts was
      two to three times lower than in S. reticuli, indicating the absence of positive
      regulatory elements. Like S. reticuli, they processed the Avicelase to its
      catalytic domain and to an enzymatically inactive part. The cel-1 gene with its
      original upstream region was not expressed within Escherichia coli. When cel-1
      had been fused in phase with the lacZ gene, large quantities of the fusion
      protein were produced in E. coli. However, this protein was enzymatically
      inactive and proteolytically degraded to a series of truncated forms. As the
      cellulase (Avicelase) synthesized by S. reticuli is not cleaved by the E. coli
      proteases, its posttranslational modification is proposed. With Bacillus subtilis
      as host, the cel-1 gene was expressed neither under its own promoter nor under
      the control of a strong Bacillus promoter.

PMID- 7574586
TI  - PCR for direct detection of indigenous uncultured magnetic cocci in sediment and
      phylogenetic analysis of amplified 16S ribosomal DNA.
AB  - PCR primers specific to the 16S ribosomal DNA (rDNA) of magnetic cocci were
      designed and used to amplify DNA from magnetically isolated magnetic cocci. The
      PCR products were subcloned by ligation into plasmid vector pCRII, and five
      clones containing approximately 270-bp fragments of amplified DNA were sequenced.
      The specific primers were also used to detect magnetic coccus 16S rDNA in
      environmental samples. Magnetic coccus 16S rDNA was amplified from the water
      column above sediment kept in an anoxic environment in the laboratory, but little
      was amplified from a water column kept in an oxic environment. These results
      suggest that magnetic cocci in the water column in an anoxic environment had
      migrated there from the sediment as a response to the microoxic or anoxic
      conditions, rather than having been present previously in a nonmagnetic form and
      having become magnetic due to these conditions. The specific primers were also
      used to detect magnetic cocci in aquatic sediment. DNA was extracted from
      sediment by direct lysis and purified for use as a PCR template by
      electrophoresis on an agarose-polyvinylpyrrolidone gel. 16S rDNA was then
      amplified and subcloned, and two clones were sequenced. The clones were screened
      for chimeric DNA by comparing sections of each with the GenBank database.

PMID- 7574587
TI  - Bacteriostatic effect of orally administered bovine lactoferrin on proliferation
      of Clostridium species in the gut of mice fed bovine milk.
AB  - When milk-fed mice were orally inoculated with Clostridium ramosum C1, this
      strain proliferated in the gut and became the dominant component of the fecal
      microflora. In this experimental model, bovine lactoferrin (bLF) administered
      with milk suppressed the proliferation of this strain in vivo and decreased the
      numbers of C. ramosum and other bacteria in the feces. This bacteriostatic effect
      of bLF was dependent on the concentration of bLF, the duration of feeding, and
      the administered dose of C. ramosum C1. Compared with bovine serum albumin,
      ovalbumin, bovine whey protein isolate, or bovine casein, only bLF showed this
      specific activity. A similar effect of bLF was observed after oral inoculation
      with C. ramosum JCM 1298, C. paraputrificum VPI 6372, or C. perfringens ATCC
      13124. A hydrolysate prepared by digestion of bLF with porcine pepsin showed the
      same inhibitory effect on proliferation of C. ramosum in vivo as occurred with
      undigested bLF. These results indicate that ingested bLF can exert a
      bacteriostatic effect against clostridia in the gut even after it has been
      digested to some extent.

PMID- 7574588
TI  - Species limits in Rhizobium populations that nodulate the common bean (Phaseolus
      vulgaris).
AB  - Evolutionary genetic relationships among 146 bean-nodulating Rhizobium strains,
      including 94 field isolates from three localities in Colombia and 36 strains from
      Mexico, were examined by multilocus enzyme electrophoresis and restriction
      fragment length polymorphism analysis of a PCR-amplified 260-bp segment of the
      16S rRNA gene. Seventy-five electrophoretic types (ETs), corresponding to
      multilocus enzyme genotypes, were identified, including a genotypically diverse
      group of 18 ETs in Colombia that is strongly differentiated from the ETs of R.
      etli, which occur in Mexico, Colombia, and Brazil. Most strains of the
      distinctive Colombian ETs carried the same 16S rRNA allele as did strains of R.
      etli, but, surprisingly, 17 isolates of two of these ETs had the allele that is
      characteristic of R. leguminosarum, and strains of two other divergent groups of
      ETs were also polymorphic for the two alleles. No fully satisfactory explanation
      for the occurrence of the R. leguminosarum 16S rRNA allele in three distantly
      related groups of strains is available, but horizontal transfer and recombination
      of the gene, in whole or in part, would seem to be more plausible than
      convergence in nucleotide sequence.

PMID- 7574589
TI  - Identification of exopolysaccharides produced by fluorescent pseudomonads
      associated with commercial mushroom (Agaricus bisporus) production.
AB  - The acidic exopolysaccharides (EPSs) from 63 strains of mushroom production
      associated fluorescent pseudomonads which were mucoid on Pseudomonas agar F
      medium (PAF) were isolated, partially purified, and characterized. The strains
      were originally isolated from discolored lesion which developed postharvest on
      mushroom (Agaricus bisporus) caps or from commercial lots of mushroom casing
      medium. An acidic galactoglucan, previously named marginalan, was produced by
      mucoid strains of the saprophyte Pseudomonas putida and the majority of mucoid
      strains of saprophytic P. fluorescens (biovars III and V) isolated from casing
      medium. One biovar II strain (J1) of P. fluorescens produced alginate, a
      copolymer of mannuronic and guluronic acids, and one strain (H13) produced an
      apparently unique EPS containing neutral and amino sugars. Of 10 strains of the
      pathogen "P. gingeri," the causal agent of mushroom ginger blotch, 8 gave mucoid
      growth on PAF. The "P. gingeri" EPS also was unique in containing both neutral
      sugar and glucuronic acid. Mucoid, weakly virulent strains of "P. reactans"
      produced either alginate or marginalan. All 10 strains of the pathogen P.
      tolaasii, the causal agent of brown blotch of mushrooms were nonnmucoid on PAF.
      Production of EPS by these 10 strains plus the 2 nonmucoid strains of "P.
      gingeri" also was negative on several additional solid media as well as in two
      broth media tested. The results support our previous studies indicating that
      fluorescent pseudomonads are a rich source of novel EPSs.

PMID- 7574590
TI  - Cloning and characterization of a gene encoding a cell-bound, extracellular beta
      glucosidase in the yeast Candida wickerhamii.
AB  - The ability of yeasts to ferment cellodextrins is rare. Candida wickerhamii is
      able to use these sugars for alcohol production because of a cell-bound,
      extracellular, beta-glucosidase that is unusual by not being inhibited by
      glucose. A cDNA expression library in lambda phage was prepared with mRNA
      isolated from cellobiose-grown C. wickerhamii. Immunological screening of the
      library with polyclonal antibodies against purified C. wickerhamii cell-bound,
      extracellular beta-glucosidase yielded 12 positive clones. Restriction
      endonuclease analysis and sequence data revealed that the clones could be divided
      into two groups, bglA and bglB, which were shown to be genetically distinct by
      Southern hybridization analyses. Efforts were directed at the study of bglB since
      it appeared to code for the cell-bound beta-glucosidase. Sequence data from both
      cDNA and genomic clones showed the absence of introns in bglB. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and immunoblotting of cell lysates
      from Escherichia coli bglB clones confirmed the presence of an expressed protein
      with an apparent molecular mass of 72 kDa, which is consistent with that expected
      for an unglycosylated form of the enzyme. Amino acid comparisons of BglB with
      other beta-glucosidase sequences suggest that it is a member of family 1 glycosyl
      hydrolases but is unusual in that it contains an additional 100 to 130 amino
      acids at the N terminus. This sequence did not have homologies to other known
      protein sequences and may impart unique properties to this beta-glucosidase.

PMID- 7574591
TI  - Evidence for anaerobic syntrophic benzoate degradation threshold and isolation of
      the syntrophic benzoate degrader.
AB  - An anaerobic, motile, gram-negative, rod-shaped, syntrophic, benzoate-degrading
      bacterium, strain SB, was isolated in pure culture with crotonate as the energy
      source. Benzoate was degraded only in association with an H2-using bacterium. The
      kinetics of benzoate degradation by cell suspensions of strain SB in coculture
      with Desulfovibrio strain G-11 was studied by using progress curve analysis. The
      coculture degraded benzoate to a threshold concentration of 214 nM to 6.5 microM,
      with no further benzoate degradation observed even after extended incubation
      times. The value of the threshold depended on the amount of benzoate added and,
      consequently, the amount of acetate produced. The addition of sodium acetate, but
      not that of sodium chloride, affected the threshold value; higher acetate
      concentrations resulted in higher threshold values for benzoate. When a cell
      suspension that had reached a threshold benzoate concentration was reamended with
      benzoate, benzoate was used without a lag. The hydrogen partial pressure was very
      low and formate was not detected in cell suspensions that had degraded benzoate
      to a threshold value. The Gibbs free energy change calculations showed that the
      degradation of benzoate was favorable when the threshold was reached. These
      studies showed that the threshold for benzoate degradation was not caused by
      nutritional limitations, the loss of metabolic activity, or inhibition by
      hydrogen or formate. The data are consistent with a thermodynamic explanation for
      the existence of a threshold, but a kinetic explanation based on acetate
      inhibition may also account for the existence of a threshold.

PMID- 7574592
TI  - Concentration and purification of beef extract mock eluates from water samples
      for the detection of enteroviruses, hepatitis A virus, and Norwalk virus by
      reverse transcription-PCR.
AB  - In this study we developed a concentration and purification procedure to
      facilitate reverse transcription (RT)-PCR detection of enteric viruses in water
      sample concentrates obtained by conventional filter adsorption-elution methods.
      One liter of beef extract-glycine eluate with or without humic acid and seeded
      with poliovirus type 1, hepatitis A virus, and Norwalk virus was used as a model
      system, and the eluent was further processed for RT-PCR compatibility. The sample
      concentration and purification procedures which we used included polyethylene
      glycol precipitation, Pro-Cipitate precipitation, a second polyethylene glycol
      precipitation, spin column chromatography, and ultrafiltration. The sample
      volumes were reduced from 1 liter to 20 to 50 microliters, and the samples were
      purified enough so that viruses could be detected by the RT-PCR. The ability to
      detect low levels of enteric viruses by molecular techniques was compared
      directly with the ability to detect enteric viruses by cell culture infectivity
      procedures. As little as 3 PFU of poliovirus type 1 in an initial 1 liter of mock
      eluate was detected by the RT-PCR.

PMID- 7574593
TI  - Cloning and sequencing of the genes involved in glyphosate utilization by
      Pseudomonas pseudomallei.
AB  - Thirty-four strains of Pseudomonas pseudomallei isolated from soil were selected
      for their ability to degrade the phosphonate herbicide glyphosate. All strains
      tested were able to grow on glyphosate as the only phosphorus source without the
      addition of aromatic amino acids. One of these strains, P. pseudomallei 22,
      showed 50% glyphosate degradation in 40 h in glyphosate medium. From a genomic
      library of this strain constructed in pUC19, we have isolated a plasmid carrying
      a 3.0-kb DNA fragment which confers to E. coli the ability to use glyphosate as a
      phosphorus source. This 3.0-kb DNA fragment from P. pseudomallei contained two
      open reading frames (glpA and glpB) which are involved in glyphosate tolerance
      and in the modification of glyphosate to a substrate of the Escherichia coli
      carbon-phosphorus lyase. glpA exhibited significant homology with the E. coli
      hygromycin phosphotransferase gene. It was also found that the hygromycin
      phosphotransferase genes from both P. pseudomallei and E. coli confer tolerance
      to glyphosate.

PMID- 7574594
TI  - Possible regulatory role for nonaromatic carbon sources in styrene degradation by
      Pseudomonas putida CA-3.
AB  - Styrene metabolism in styrene-degrading Pseudomonas putida CA-3 cells has been
      shown to proceed via styrene oxide, phenylacetaldehyde, and phenylacetic acid.
      The initial step in styrene degradation by strain CA-3 is oxygen-dependent
      epoxidation of styrene to styrene oxide, which is subsequently isomerized to
      phenylacetaldehyde. Phenylacetaldehyde is then oxidized to phenylacetic acid.
      Styrene, styrene oxide, and phenylacetaldehyde induce the enzymes involved in the
      degradation of styrene to phenylacetic acid by P. putida CA-3. Phenylacetic acid
      induced cells do not oxidize styrene or styrene oxide. Thus, styrene degradation
      by P. putida CA-3 can be subdivided further into an upper pathway which consists
      of styrene, styrene oxide, and phenylacetaldehyde and a lower pathway which
      begins with phenylacetic acid. Studies of the repression of styrene degradation
      by P. putida CA-3 show that glucose has no effect on the activity of styrene
      degrading enzymes. However, both glutamate and citrate repress styrene
      degradation and phenylacetic acid degradation, showing a common control mechanism
      on upper pathway and lower pathway intermediates.

PMID- 7574595
TI  - Multiple genes encoding 2,3-dihydroxybiphenyl 1,2-dioxygenase in the gram
      positive polychlorinated biphenyl-degrading bacterium Rhodococcus erythropolis
      TA421, isolated from a termite ecosystem.
AB  - Rhodococcus erythropolis TA421 was isolated from a termite ecosystem and is able
      to degrade a wide range of polychlorinated biphenyl (PCB) congeners. Genetic and
      biochemical analyses of the PCB catabolic pathway of this organism revealed that
      there are four different bphC genes (bphC1, bphC2, bphC3, and bphC4) which encode
      2,3-dihydroxybiphenyl dioxygenases. As determined by Southern hybridization, none
      of the bphC genes exhibits homology to any other bphC gene. bphC1, bphC2, and
      bphC4 encode enzymes that have narrow substrate specificities and cleave the
      first aromatic ring in the meta position. In contrast, bphC3 encodes a meta
      cleavage dioxygenase with broad substrate specificity. Asturias et al. have shown
      that the closely related organism Rhodococcus globerulus P6 contains three
      different bphC genes (bphC1, bphC2, and bpHC3) which encode meta cleavage
      dioxygenases. The data suggest that there is a diverse family of bphC genes which
      encode PCB meta cleavage dioxygenases in members of the genus Rhodococcus.

PMID- 7574596
TI  - Pathotypes in the Entomophaga grylli species complex of grasshopper pathogens
      differentiated with random amplification of polymorphic DNA and cloned-DNA
      probes.
AB  - The zygomycetous fungus Entomophaga grylli is a pathogen that shows host-specific
      variance to grasshopper subfamilies. Three pathotypes of the E. grylli species
      complex were differentiated by three molecular techniques. In the first method,
      the three pathotypes showed different fragment patterns generated by random
      amplification of polymorphic DNA (RAPD). There was little or no interisolate
      variability in RAPD fragment patterns within each pathotype. Passage of an
      isolate of pathotype 3, originally from an Australian grasshopper (Praxibulus
      sp.), through a North America grasshopper resulted in no differences in the
      resultant RAPD fragment patterns. In the second method, polymorphic RAPD
      fragments were used to probe the genomic DNA from the three pathotypes, and
      pathotype-specific fragments were found. In the third method, restriction
      fragments from genomic DNA of the three pathotypes were cloned and screened for
      pathotype specificity. A genomic probe specific for each pathotype was isolated.
      These probes did not hybridize to DNA from Entomophaga aulicae or from
      grasshoppers. To facilitate the use of RAPD analysis and other molecular tools to
      identify pathotypes, a method for extracting DNA from resting spores from
      infected grasshoppers was developed. The DNA from the fractured resting spores
      was of sufficient integrity to be blotted and probed with the pathotype-specific
      DNA probes, thus validating the use of these probes for pathotype identification
      in field-collected grasshoppers.

PMID- 7574597
TI  - Cloning and molecular analysis of the dihydrofolate reductase gene from
      Lactococcus lactis.
AB  - The Lactococcus lactis gene encoding trimethoprim resistance has been cloned and
      expressed in Escherichia coli and Bacillus subtilis. Several lines of evidence
      indicate that the cloned gene encodes dihydrofolate reductase (DHFR). (i) It
      fully complements the fol "null" mutation in E. coli. (ii) Nucleotide sequencing
      of the cloned fragment revealed the presence of one open reading frame encoding a
      protein that shares homology with the family of bacterial DHFR enzymes. (iii)
      Overexpression of this open reading frame in E. coli resulted in the appearance
      in cell extracts of a protein of the expected size as well as in a dramatic
      increase of DHFR activity. In cell extracts, the DHFR activity was not inhibited
      by low trimethoprim concentration. By Northern (RNA) blotting and primer
      extension analyses, the size and the start point of the dhfr transcript,
      respectively, have been determined. Results of these experiments indicate that in
      L. lactis the dhfr gene represents part of a larger transcription unit.

PMID- 7574598
TI  - Isolation and characterization of a heat-stable pullulanase from the
      hyperthermophilic archaeon Pyrococcus woesei after cloning and expression of its
      gene in Escherichia coli.
AB  - The gene encoding an extremely heat-stable pullulanase from the hyperthermophilic
      archaeon Pyrococcus woesei was cloned and expressed in Escherichia coli.
      Purification of the enzyme to homogeneity was achieved after heat treatment of
      the recombinant E. coli cells, affinity chromatography on a maltotriose-coupled
      Sepharose 6B column, and anion-exchange chromatography on Mono Q. The
      pullulanase, which was purified 90-fold with a final yield of 15%, is composed of
      a single polypeptide chain with a molecular mass of 90 kDa. The enzyme is
      optimally active at 100 degrees C and pH 6.0 and shows 40% activity at 120
      degrees C. Enzyme activation up to 370% is achieved in the presence of calcium
      ions and reducing agents such as beta-mercaptoethanol and dithiothreitol, whereas
      N-bromosuccinimide and alpha-cyclodextrin are inhibitory. The high rigidity of
      the heat-stable enzyme is demonstrated by fluorescence spectroscopic studies in
      the presence of denaturing agents such as sodium dodecyl sulfate. At temperatures
      above 80 degrees C, the enzyme seems to switch from the compact to the unfolded
      form, which is accompanied by an apparent shift in the molecular mass from 45 to
      90 kDa.

PMID- 7574599
TI  - Ruminal microbial digestion in free-living, in captive lichen-fed, and in starved
      reindeer (Rangifer tarandus tarandus) in winter.
AB  - In free-living (FL) reindeer eating a natural mixed winter diet dominated by
      lichens, captive (CF) reindeer fed pure lichens ad libitum, and CF reindeer
      subsequently starved for 1 day (CS1 reindeer) or 4 days (CS4 reindeer), the
      dominant rumen anaerobic bacteria were characterized, their population densities
      were estimated, and ruminal pH and volatile fatty acid concentrations were
      determined. In the FL reindeer, the total median viable anaerobic bacterial
      population ranged from 18 x 10(8) to 35 x 10(8) cells per ml of rumen fluid (n =
      4), compared with 26 x 10(8) to 34 x 10(8) and 0.09 x 10(8) to 0.1 x 10(8) cells
      per ml of rumen fluid in CF reindeer (n = 2) and CS4 reindeer (n = 2),
      respectively. The median bacterial population adhering to the rumen solids ranged
      from 260 x 10(8) to 450 x 10(8), 21 x 10(8) to 38 x 10(8), and 0.5 x 10(8) cells
      per g (wet weight) of rumen solids in FL, CF, and CS4 reindeer, respectively.
      Although there were variations in the rumen bacterial composition among the FL
      reindeer (n = 4), strains of Bacteroides, Fibrobacter, Streptococcus, and
      Clostridium dominated in the rumen fluid. Streptococcus spp. and Clostridium spp.
      were the dominant bacteria in the CF reindeer (n = 2), while in the CS4 reindeer
      (n = 2) the dominant bacteria were Fusobacterium spp., members of the family
      Enterobacteriaceae, and Eubacterium spp. Transmission electron micrographs of
      lichen particles from the rumen of one FL reindeer, one CF reindeer, and one CS4
      reindeer show bacteria resembling Bacteroides spp. adhering to the lichen
      particles, evidently digesting the lichen hyphae from the inside.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7574600
TI  - Correlation of brightening with cumulative enzyme activity related to lignin
      biodegradation during biobleaching of kraft pulp by white rot fungi in the solid
      state fermentation system.
AB  - Biobleaching of hardwood unbleached kraft pulp (UKP) by Phanerochaete
      chrysosporium and Trametes versicolor was studied in the solid-state fermentation
      system with different culture media. In this fermentation system with low
      nitrogen and high-carbon culture medium, pulp brightness increased by 15 and 30
      points after 5 days of treatment with T. versicolor and P. chrysosporium,
      respectively, and the pulp kappa number decreased with increasing brightness. A
      comparison of manganese peroxidase (MnP), lignin peroxidase (LiP), and laccase
      activities assayed by using fungus-treated pulp and the filtrate after
      homogenizing the fungus-treated pulp in buffer solution indicated that enzymes
      secreted from fungi were adsorbed onto the UKP and that assays of these enzyme
      activities should be carried out with the treated pulp. Time course studies of
      brightness increase and MnP activity during treatment with P. chrysosporium
      suggested that it was difficult to correlate them on the basis of data obtained
      on a certain day of incubation, because the MnP activity fluctuated dramatically
      during the treatment time. When brightness increase and cumulative MnP, LiP, and
      laccase activities were determined, a linear relationship between brightness
      increase and cumulative MnP activity was found in the solid-state fermentation
      system with both P. chrysosporium and T. versicolor. This result suggests that
      MnP is involved in brightening of UKP by white rot fungi.

PMID- 7574601
TI  - Factors which affect the frequency of sporulation and tetrad formation in
      Saccharomyces cerevisiae baker's yeasts.
AB  - To clarify the role that respiration, the mitochondrial genome, and interactions
      of mitochondria and nucleus play on sporulation and to improve the sporogenic
      ability of several baker's yeasts, an investigation of the effects of different
      media and culture conditions on baker's yeast sporulation was undertaken. When
      standard protocols were followed, the sporulation frequency varied between 20 and
      60% and the frequency of four-spore asci varied between 1 and 6%. Different
      presporulation and sporulation media, the use of solid versus liquid media, and
      incubation at 22 versus 30 degrees C were checked, and the cells were collected
      from presporulation media in either exponential or stationary phase. Best
      results, yielding sporulation and four-spore ascus formation frequencies up to 97
      and 60%, respectively, were obtained by collection of the cells in exponential
      phase from liquid presporulation medium with 10% glucose and transfer of them to
      sporulation medium with 0.5% potassium acetate at 22 degrees C. Under these
      conditions, the most important factor was the growth phase (exponential versus
      stationary) at which cells from presporulation medium were collected. Changes in
      sporulation frequencies were also measured after transfer of mitochondria from
      different sources to baker's yeasts. When mitochondria from laboratory, baker's,
      and wine yeasts were transferred to baker's and laboratory petite strains,
      sporulation and four-spore ascus formation frequencies dropped dramatically
      either to no sporulation at all or to less than 50% in both parameters. This
      transfer also resulted in an increase in the frequency of petite mutant formation
      but yielded similar growth and respiration rates in glycerol.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7574602
TI  - Isolation of a cold-sensitive fermentation mutant of a baker's yeast strain and
      its use in a refrigerated dough process.
AB  - Conventional baker's yeast converts sugars in dough into CO2 and ethanol to a
      significant extent when the dough is stored for days at 5 degrees C. We have
      isolated Csf (cold-sensitive fermentation) mutants of a commercial baker's yeast
      by a selection method including as the critical step a nystatin treatment to
      mutagenized cells at 10 degrees C in the presence of antimycin A. The
      fermentative activity of mutant strain CSF3 was substantially zero at 5 degrees C
      and one-fifth that of the parent at 10 degrees C but was restored to the same
      level as the parental activity at 25 to 40 degrees C. In contrast with the
      parent, the mutant strain normally produced white bread dough and butter roll
      dough even after the dough was stored for a week at 5 degrees C.

PMID- 7574603
TI  - Minimized virus binding for tests of barrier materials.
AB  - Viruses are used to test the barrier properties of materials. Binding of virus
      particles during passage through holes in the material may yield misleading test
      results. The choices of challenge virus and suspending medium may be important
      for minimizing confounding effects that might arise from such binding. In this
      study, different surrogate viruses, as well as different support media, were
      evaluated to determine optimal test parameters. Two membranes with high-binding
      properties (nitrocellulose and cationic polysulfone) were used as filters to
      compare binding activities of different surrogate challenge viruses (MS2, phi
      X174, T7, PRD1, and phi 6) in different media. The media consisted of buffered
      saline with surfactants, serum, or culture broth as additives. In addition,
      elution rates of viruses that bound to the membranes were determined. The results
      suggest that viruses can bind by hydrophobic and electrostatic interactions, with
      phi X174 displaying the lowest level of binding by either process. The nonionic
      detergents Triton X-100 and Tween 80 (0.1%) equally minimized hydrophobic
      interactions. Neither anionic nor cationic surfactants were as effective at
      nontoxic levels. Serum was effective at reducing both hydrophobic and
      electrostatic binding, with 2% being sufficient for eliminating binding under our
      test conditions. Thus, phi X174 remains the best choice as a surrogate virus to
      test barrier materials, and Triton X-100 (0.1%) remains a good choice for
      reducing hydrophobic binding. In addition, binding of viruses by barrier
      materials is unlikely to prevent passage of blood-borne pathogens.

PMID- 7574604
TI  - Expression vectors for the use of eukaryotic luciferases as bacterial markers
      with different colors of luminescence.
AB  - An easy way to identify microorganisms is to provide them with gene markers that
      confer a unique phenotype. Several genetic constructions were developed to use
      eukaryotic luciferase genes for bacterial tagging. The firefly and click bettle
      luciferase genes, luc and lucOR, respectively, were cloned under constitutive
      control and regulated control from different transcriptional units driven by P1,
      lambda PR, and Ptrc promoters. Comparison of the expression of each gene in
      Escherichia coli cells from identical promoters showed that bioluminescence
      produced by luc could be detected luminometrically in a more sensitive manner. In
      contrast, luminescence from intact lucOR-expressing cells was much more stable
      and resistant to high temperatures than that from luc-expressing cells. To
      analyze the behavior of these constructions in other gram-negative bacteria, gene
      fusions with luc genes were cloned on broad-host-range vectors. Measurements of
      light emission from Rhizobium meliloti, Agrobacterium tumefaciens, and
      Pseudomonas putida cells indicated that both luciferases were poorly expressed
      from P1 in most bacterial hosts. In contrast, the lambda promoter PR yielded
      constitutively high levels of luciferase expression in all bacterial species
      tested. PR activity was not regulated by temperature when the thermosensitive
      repressor cI857 was present in the bacterial species tested, except for E. coli.
      In contrast, the regulated lacIq-Ptrc::lucOR fusion expression system behaved in
      a manner similar to that observed in E. coli cells. After IPTG (isopropyl-beta-D
      thiogalactopyranoside) induction, this system produced the highest levels of
      lucOR expression in all bacterial species tested.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7574605
TI  - Mineralization of mono- and dichlorobenzenes and simultaneous degradation of
      chloro- and methyl-substituted benzenes by the white rot fungus Phanerochaete
      chrysosporium.
AB  - Phanerochaete chrysosporium extensively degraded and mineralized chlorobenzene
      and o-, m-, and p-dichlorobenzenes. The rate of degradation was in the following
      order: monochlorobenzene > m-dichlorobenzene > o-dichlorobenzene > p
      dichlorobenzene. Net level of degradation was generally higher than
      mineralization. Maximal degradation and mineralization of chlorobenzenes were
      observed in malt extract cultures in which the lignin peroxidases and manganese
      peroxidases are not known to be produced. The fungus degraded both chlorobenzene
      and toluene when presented as a mixture, indicating its ability to simultaneously
      degrade chloro-substituted and methyl-substituted benzenes.

PMID- 7574606
TI  - Comparison of fungi within the Gaeumannomyces-Phialophora complex by analysis of
      ribosomal DNA sequences.
AB  - Four ascomycete species of the genus Gaeumannomyces infect roots of
      monocotyledons. Gaeumannomyces graminis contains four varieties, var. tritici,
      var. avenae, var. graminis, and var. maydis. G. graminis varieties tritici,
      avenae, and graminis have Phialophora-like anamorphs and, together with the other
      Gaeumannomyces and Phialophora species found on cereal roots, constitute the
      Gaeumannomyces-Phialophora complex. Relatedness of a number of Gaeumannomyces and
      Phialophora isolates was assessed by comparison of DNA sequences of the 18S rRNA
      gene, the 5.8S rRNA gene, and the internal transcribed spacers (ITS). G. graminis
      var. tritici, G. graminis var. avenae, and G. graminis var. graminis isolates can
      be distinguished from each other by nucleotide sequence differences in the ITS
      regions. The G. graminis var. tritici isolates can be further subdivided into R
      and N isolates (correlating with ability [R] or inability [N] to infect rye).
      Phylogenetic analysis of the ITS regions of several oat-infecting G. graminis
      var. tritici isolates suggests that these isolates are actually more closely
      related to G. graminis var. avenae. The isolates of Magnaporthe grisea included
      in the analysis showed a surprising degree of relatedness to members of the
      Gaeumannomyces-Phialophora complex. G. graminis variety-specific oligonucleotide
      primers were used in PCRs to amplify DNA from cereal seedlings infected with G.
      graminis var. tritici or G. graminis var. avenae, and these should be valuable
      for sensitive detection of pathogenic isolates and for diagnosis of take-all.

PMID- 7574607
TI  - Evaluation of the immunofluorescence procedure for detection of Giardia cysts and
      Cryptosporidium oocysts in water.
AB  - The accurate determination of the presence of Giardia cysts and Cryptosporidium
      oocysts in surface waters requires a reliable method for the detection and
      enumeration of these pathogenic organisms. Published methods have usually
      reported recovery efficiencies of less than 50% for both cysts and oocysts.
      Typically, the losses are greater for Cryptosporidium oocysts than they are for
      Giardia cysts. The purpose of this study was to examine procedures used for
      sample collection, elution, concentration, and clarification to determine when
      losses of cysts and oocysts occurred during processing. The results showed that
      major losses of cysts and oocysts occurred during centrifugation and
      clarification. Depending on the centrifugation force, oocyst losses of as high as
      30% occurred for each centrifugation step. A 1.15-specific-gravity Percoll
      sucrose gradient was needed to optimize recovery of oocysts from natural water
      samples. Minor improvements in the procedure could be accomplished by selecting a
      filter other than the recommended 1-micron-pore-size (nominal-porosity)
      polypropylene filter.

PMID- 7574608
TI  - The abundance of Zoogloea ramigera in sewage treatment plants.
AB  - Zoogloea ramigera has long been considered the typical activated sludge bacterium
      responsible for the formation of activated sludge flocs. On the basis of the
      results of a comparative sequence analysis, we designed three oligonucleotide
      probes complementary to characteristic regions of the 16S rRNAs of Z. ramigera
      ATCC 19544T (T = type strain) and two misclassified strains, Z. ramigera ATCC
      25935 and ATCC 19623. Dissociation temperatures were determined, and probe
      specificities, as well as the potential of probes for whole-cell hybridization,
      were evaluated by using numerous reference organisms. Several activated sludge
      samples were examined with these probes by using both the in situ and dot blot
      hybridization methods. Only the type strain probe hybridized to cells that
      accumulated in the typical branched gelatinous matrices, the so-called Zoogloea
      fingers. This probe revealed cells in most of the activated sludge samples
      studied. We found that relatively high levels of Z. ramigera cells (up to
      approximately 10% of the total number of cells) and typical morphology tended to
      be linked to overloading of sewage plants. The probe directed to rejected type
      strain Z. ramigera ATCC 19623 bound to only a few cells. Cells that reacted with
      the probe complementary to Z. ramigera ATCC 25935, which was originally isolated
      from a trickling filter, were not observed in activated sludge.

PMID- 7574609
TI  - Mechanisms of yeast flocculation: comparison of top- and bottom-fermenting
      strains.
AB  - The flocculation of two brewing yeast strains, top-fermenting strain
      Saccharomyces cerevisiae MUCL 38485 and bottom-fermenting strain Saccharomyces
      carlsbergensis MUCL 28285, has been investigated by means of a turbidimetric
      test. The two strains showed different electrical properties, a different
      hydrophobicity, and a different surface chemical composition. They flocculated
      according to completely different mechanisms; however, no correlation between the
      cell physicochemical properties and the onset of flocculation was found for
      either strain. Flocculation of the bottom strain was governed by a lectin
      mediated mechanism. It was inhibited by mannose and some other sugars, required
      calcium specifically, occurred in a narrow pH range different from the
      isoelectric point, and was not influenced by ethanol. The onset of flocculation
      at the end of the exponential phase was controlled both by the appearance of
      "active" lectins at the cell surface and by the decrease in sugar concentration
      in the solution. Flocculation of the top strain was not inhibited by mannose, did
      not require the addition of calcium, and took place at the cell isoelectric
      point. Low concentrations of ethanol broadened the pH range in which the cells
      flocculated, and flocculation was favored by an increase of ionic strength.
      Adsorbed ethanol may induce flocculation by reducing the electrostatic repulsion
      between cells, by decreasing steric stabilization, and/or by allowing the
      protrusion of polymer chains into the liquid phase. The onset of flocculation was
      controlled by both a change of the cell surface and an increase in ethanol
      concentration. The only evidence for an adhesin-mediated mechanism was the
      specific requirement for a small amount of calcium.

PMID- 7574610
TI  - Purification and characterization of two thermostable acetyl xylan esterases from
      Thermoanaerobacterium sp. strain JW/SL-YS485.
AB  - Two acetyl esterases (EC 3.1.1.6) were purified to gel electrophoretic
      homogeneity from Thermoanaerobacterium sp. strain JW/SL-YS485, an anaerobic,
      thermophilic endospore former which is able to utilize various substituted xylans
      for growth. Both enzymes released acetic acid from chemically acetylated larch
      xylan. Acetyl xylan esterases I and II had molecular masses of 195 and 106 kDa,
      respectively, with subunits of 32 kDa (esterase I) and 26 kDa (esterase II). The
      isoelectric points were 4.2 and 4.3, respectively. As determined by a 2-min assay
      with 4-methylumbelliferyl acetate as the substrate, the optimal activity of
      acetyl xylan esterases I and II occurred at pH 7.0 and 80 degrees C and at pH 7.5
      and 84 degrees C, respectively. Km values of 0.45 and 0.52 mM 4
      methylumbelliferyl acetate were observed for acetyl xylan esterases I and II,
      respectively. At pH 7.0, the temperatures for the 1-h half-lives for acetyl xylan
      esterases I and II were 75 degrees and slightly above 100 degrees C,
      respectively.

PMID- 7574611
TI  - Use of suppressor analysis to find genes involved in the colonization deficiency
      of a Bacteroides thetaiotaomicron mutant unable to grow on the host-derived
      mucopolysaccharides chondroitin sulfate and heparin.
AB  - Bacteroides thetaiotaomicron, one of the numerically predominant species of human
      colonic bacteria, can ferment two types of host-derived mucopolysaccharides,
      chondroitin sulfate (CS) and heparin (HP). Originally, the pathways for
      utilization of CS and HP appeared to be completely independent of each other, but
      we have recently identified a gene, chuR, that links the two utilization systems.
      chuR is probably a regulatory gene, but it controls only a small subset of genes
      involved in CS and HP utilization. Some of the genes controlled by chuR are
      important for survival of B. thetaiotaomicron in the colon because a mutant that
      no longer produced ChuR was unable to compete with the wild type for colonization
      of the intestinal tract of germfree mice. In an attempt to identify genes that
      either were controlled by ChuR or encoded proteins that interacted with ChuR, we
      used transposon mutagenesis to generate suppressor mutations that restored the
      ability of a chuR disruption mutant to grow on CS and HP. Two classes of
      suppressors were isolated. One class grew as well as the wild type on CS and HP
      and had recovered the ability to compete with the wild type for colonization of
      the germfree mouse intestinal tract. A second class grew more slowly on CS and HP
      and reached only a half-maximum level on CS. This mutant still had a colonization
      defect. Representatives of both classes of suppressor mutants have been
      characterized, and the results of this analysis suggest that the transposon
      insertions in the suppressor mutants probably affected regulatory genes whose
      products interact with ChuR.

PMID- 7574612
TI  - Isolation and characterization of RNA from low-biomass deep-subsurface sediments.
AB  - Three methods for the isolation of microbial RNA from low-biomass deep-subsurface
      sediments have been developed and evaluated. RNA was isolated from samples taken
      from depths ranging from 173 to 217 m, and samples represented a variety of
      lithologies, including lacustrine, fluvial sand, and paleosol sediments. Cell
      numbers in these samples were estimated to be between log 4.0 and log 5.1/g on
      the basis of phospholipid fatty acid analysis. The most efficient method examined
      is based on the direct lysis of microbial cells followed by the extraction of RNA
      with alkaline phosphate buffers and subsequent inactivation of nucleases by
      extraction with guanidinium isothiocyanate. Estimated recoveries of mRNA for this
      method are approximately 26%. The recovered RNA included both mRNA and rRNA, as
      evidenced by the detection of sequences homologous to transcripts from the
      toluene-4-monooxygenase gene of Pseudomonas mendocina KR1 and bacterial,
      archaeal, and eukaryotic rRNA. An unexpectedly high relative concentration of
      archaeal rRNA (22 to 40%) was observed for these samples.

PMID- 7574613
TI  - Channel structures in aerobic biofilms of fixed-film reactors treating
      contaminated groundwater.
AB  - Scanning electron microscopy, confocal scanning laser microscopy, and fatty acid
      methyl ester profiles were used to study the development, organization, and
      structure of aerobic multispecies biofilm communities in granular activated
      carbon (GAC) fluidized-bed reactors treating petroleum-contaminated groundwaters.
      The sequential development of biofilm structure was studied in a laboratory
      reactor fed toluene-amended groundwater and colonized by the indigenous aquifer
      populations. During the early stages of colonization, microcolonies were observed
      primarily in crevices and other regions sheltered from hydraulic shear forces.
      Eventually, these microcolonies grew over the entire surface of the GAC. This
      growth led to the development of discrete discontinuous multilayer biofilm
      structures. Cell-free channel-like structures of variable sizes were observed to
      interconnect the surface film with the deep inner layers. These interconnections
      appeared to increase the biological surface area per unit volume ratio, which may
      facilitate transport of substrates into and waste products out of deep regions of
      the biofilm at rates greater than possible by diffusion alone. These
      architectural features were also observed in biofilms from four field-scale GAC
      reactors that were in commercial operation treating petroleum-contaminated
      groundwaters. These shared features suggest that formation of cell-free channel
      structures and their maintenance may be a general microbial strategy to deal with
      the problem of limiting diffusive transport in thick biofilms typical of
      fluidized-bed reactors.

PMID- 7574615
TI  - Polyclonal antibodies to chlorosome proteins as probes for green sulfur bacteria.
AB  - We found that polyclonal antibodies raised against chlorosome polypeptides from
      green sulfur bacteria reacted to Chlorobium tepidum, Chlorobium limicola, and
      Chlorobium phaeobacteroides but not to Chloroflexus aurantiacus. These antibodies
      successfully labeled only green sulfur species in marine microbial mat samples.
      Our results suggest that these antibodies may be useful as immunohistochemical
      probes.

PMID- 7574614
TI  - Phenotypic characterization of intestinal Escherichia coli of pigs during
      suckling, postweaning, and fattening periods.
AB  - A highly discriminatory and standardized biochemical fingerprinting method was
      used to monitor the persistence and colonization of intestinal Escherichia coli
      isolated from the feces of four sows and their litters (four piglets from each)
      during the suckling, postweaning, and fattening periods. Altogether, 195 fecal
      samples were collected and 1,827 E. coli strains were tested (mean number of
      isolates tested per fecal sample per pig, 9.5). Strains were divided into
      similarity groups on the basis of their biochemical phenotypes (BPTs). The
      diversity of E. coli strains in each sample was measured with Simpson's index of
      diversity, and similarity between E. coli floras of piglets was calculated with a
      population similarity index. Each fecal sample contained several BPTs of E. coli,
      some of which dominated that population. The intestinal colonization of piglets
      consisted of successive waves of different E. coli BPTs, the tenure of which
      varied from a few days to 2 weeks. Most of these BPTs disappeared in the
      succeeding samples and were not recovered again from the same piglets. On the
      other hand, some E. coli strains which colonized piglets early during the
      suckling period persisted for a long period and were referred to as resident
      BPTs. Each piglet carried more than one resident BPT (mean of 2.4 BPTs per pig),
      some of which were also found in other piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574616
TI  - Detection and characterization of lactose-utilizing Lactococcus spp. in natural
      ecosystems.
AB  - The presence of lactose-utilizing Lactococcus species in nondairy environments
      was studied by using identification methods based on PCR amplification and
      (sub)species-specific probes derived from 16S rRNA sequences. Environmental
      isolates from samples taken on cattle farms and in the waste flow of a cheese
      production plant were first identified to the genus level, using a Lactococcus
      genus-specific probe. Isolates which showed a positive signal with this probe
      were further identified to the (sub)species level. Lactococcus lactis isolates
      were also characterized at the phenotypic level for the ability to hydrolyze
      arginine, to ferment citrate, and to produce proteases and bacteriocins. With
      specific PCR amplifications, the presence of sequences related to citP, coding
      for citrate permease; prtP, coding for protease; and nisA or nisZ, the structural
      genes for production of nisin A or nisin Z, respectively, was verified. By these
      methods, it was possible to isolate lactococci from various environmental
      sources, such as soil, effluent water, and the skin of cattle. The strains of L.
      lactis isolated differed in a number of properties, such as the ability to
      hydrolyze arginine or the absence of citP-related sequences, from those found in
      industrial starter cultures. The results indicate that the majority of the
      industrially produced lactococci do not survive outside the dairy environment,
      although natural niches are available. However, from those niches strains with
      the potential to be developed into novel starter cultures may be isolated.

PMID- 7574617
TI  - Iron-stimulated toxin production in Microcystis aeruginosa.
AB  - Nitrate- and phosphate-limited conditions had no effect on toxin production by
      Microcystis aeruginosa. In contrast, iron-limited conditions influenced toxin
      production by M. aeruginosa, and iron uptake was light dependent. A model for
      production of toxin by M. aeruginosa is proposed.

PMID- 7574618
TI  - Molecular cloning of the gene which encodes beta-N-acetylglucosaminidase from a
      marine bacterium, Alteromonas sp. strain O-7.
AB  - The gene encoding the periplasmic beta-N-acetylglucosaminidase (GlcNAcase B) from
      a marine Alteromonas sp. strain, O-7, was cloned and sequenced. The protein
      sequence of GlcNAcase B revealed a highly significant homology with Vibrio
      GlcNAcase and alpha- and beta-chains of human beta-hexosaminidase.

PMID- 7574619
TI  - Nonradioactive colony hybridization assay for detection and enumeration of
      enterotoxigenic Clostridium perfringens in raw beef.
AB  - A DNA probe endolabeled with digoxigenin by PCR was developed to detect and
      enumerate enterotoxigenic Clostridium perfringens in raw beef. After 2 h of
      hybridization, membranes were developed by using an anti-digoxigenin-alkaline
      phosphatase conjugated antibody. The resulting chromogenic reaction allowed us to
      detect and enumerate < or = 10 CFU of C. perfringens per g.

PMID- 7574620
TI  - Direct detection of Listeria monocytogenes in 25 milliliters of raw milk by a two
      step PCR with nested primers.
AB  - A method for direct detection of Listeria monocytogenes in 25 ml of raw milk is
      presented. The detection limit can be situated between 10 and 5 CFU. The
      detection method is based on chemical extraction of the milk components and PCR
      amplification with two nested pairs of primers specific for Listeria
      monocytogenes.

PMID- 7574621
TI  - Possible errors in assay for beta-glycosidase activity.
AB  - Cecal homogenates were assayed for the enzymes beta-glucosidase, beta
      glucuronidase, and beta-galactosidase. Anaerobic incubation with the addition of
      excess 3,4-dichloronitrobenzene, a substrate for nitroreductase, significantly
      increased the detection of the beta-glycosidase enzymes' activities.

PMID- 7574622
TI  - Characterization of the endosymbiont of a deep-sea bivalve, Calyptogena soyoae.
AB  - We have purified DNA from gill tissue of a marine bivalve, Calyptogena soyoae,
      collected from the deep-sea cold seep communities in Sagami Bay, Japan. An rRNA
      gene was amplified, cloned, and sequenced. In situ hybridization revealed that
      the sequence is that of a bacterial endosymbiont within the gill of C. soyoae.

PMID- 7574623
TI  - PCR detection of Ti and Ri plasmids from phytopathogenic Agrobacterium strains.
AB  - A universal primer set (VCF/VCR) for PCR analysis based on the sequences of the
      virC operon located on Ti and Ri plasmids was designed to detect these plasmids
      from phytopathogenic Agrobacterium strains. With the VCF (sequence, 5'
      ATCATTTGTAGCGACT-3') and VCR (sequence, 5'-AGCTCAAACCTGCTTC-3') primer set, DNA
      fragments of 730 bp in length were amplified from cell lysates of 10 rhizogenic
      and 65 tumorigenic agrobacteria. DNA sequencing and Southern hybridization
      analysis confirmed that the amplified fragments corresponded to the target
      region. The PCR method is considered convenient for routine determination of the
      potential pathogenicity of Agrobacterium strains.

PMID- 7574624
TI  - Purification and characterization of a dipeptidase from Lactobacillus sake.
AB  - A dipeptidase was purified from cell extracts of Lactobacillus sake. This
      compound was a monomer having a molecular weight of 50,000 and a pI of 4.7 and
      exhibited broad specificity against all dipeptides except those with proline or
      glycine at the N terminus. The enzyme was inhibited by EDTA or 1,10
      phenanthroline but could be reactivated with CoCl2 and MnCl2.

PMID- 7574625
TI  - Bacterial degradation of m-nitrobenzoic acid.
AB  - Pseudomonas sp. strain JS51 grows on m-nitrobenzoate (m-NBA) with stoichiometric
      release of nitrite. m-NBA-grown cells oxidized m-NBA and protocatechuate but not
      3-hydroxybenzoate, 4-hydroxy-3-nitrobenzoate, 4-nitrocatechol, and 1,2,4
      benzenetriol. Protocatechuate accumulated transiently when succinate-grown cells
      were transferred to media containing m-NBA. Respirometric experiments indicated
      that the conversion of m-NBA to protocatechuate required 1 mol of oxygen per mol
      of substrate. Conversions conducted in the presence of 18O2 showed the
      incorporation of both atoms of molecular oxygen into protocatechuate. Extracts of
      m-NBA-grown cells cleaved protocatechuate to 2-hydroxy-4-carboxymuconic
      semialdehyde. These results provide rigorous proof that m-NBA is initially
      oxidized by a dioxygenase to produce protocatechuate which is further degraded by
      a 4,5-dioxygenase.

PMID- 7574626
TI  - Effect of sodium hypochlorite exposure on infectivity of Cryptosporidium parvum
      oocysts for neonatal BALB/c mice.
AB  - Oocysts of Cryptosporidium parvum suspended in 5.25, 2.63, or 1.31% aqueous
      sodium hypochlorite (Clorox laundry bleach) for 10, 30, 60, or 120 min at 21
      degrees C were administered by gastric intubation to neonatal BALB/c mice.
      Microscopic examination of intestinal tissue sections revealed developmental
      stages of C. parvum in all of the mice.

PMID- 7574627
TI  - Chloroform degradation in methanogenic methanol enrichment cultures and by
      Methanosarcina barkeri 227.
AB  - The effects of methanol addition and consumption on chloroform degradation rate
      and product distribution in methanogenic methanol enrichment cultures and in
      cultures of Methanosarcina barkeri 227 were investigated. Degradation of
      chloroform with initial concentrations up to 27.3 microM in enrichment cultures
      and 4.8 microM in pure cultures was stimulated by the addition of methanol.
      However, methanol consumption was inhibited by as little as 2.5 microM chloroform
      in enrichment cultures and 0.8 microM chloroform in pure cultures, suggesting
      that the presence of methanol, not its exact concentration or consumption rate,
      was the most significant variable affecting chloroform degradation rate. Methanol
      addition also significantly increased the number of moles of dichloromethane
      produced per mole of chloroform consumed. In enrichment cultures, the number of
      moles of dichloromethane produced per mole of chloroform consumed ranged from 0.7
      (methanol consumption essentially uninhibited) to 0.35 (methanol consumption
      significantly inhibited) to less than 0.2 (methanol not added to the culture). In
      pure cultures, the number of moles of dichloromethane produced per mole of
      chloroform consumed was 0.47 when methanol was added and 0.24 when no methanol
      was added. Studies with [14C]chloroform in both enrichment and pure cultures
      confirmed that methanol metabolism stimulated dichloromethane production compared
      with CO2 production. The results indicate that while the addition of methanol
      significantly stimulated chloroform degradation in both methanogenic methanol
      enrichment cultures and cultures of M. barkeri 227, the prospects for use of
      methanol as a growth substrate for anaerobic chloroform-degrading systems may be
      limited unless the increased production of undesirable chloroform degradation
      products and the inhibition of methanol consumption can be mitigated.

PMID- 7574628
TI  - Intestinal floras of populations that have a high risk of colon cancer.
AB  - The fecal floras of polyp patients, Japanese-Hawaiians, North American
      Caucasians, rural native Japanese, and rural native Africans were compared. The
      polyp patients and Japanese-Hawaiians were considered to be groups at high risk
      of colon cancer, and the rural native Japanese and rural native Africans were
      considered to be groups at low risk. The North American Caucasians were found to
      have a flora composition intermediate between these two groups. Fifteen bacterial
      taxa from the human fecal flora were significantly associated with high risk of
      colon cancer, and five were significantly associated with low risk of colon
      cancer. Total concentrations of Bacteroides species and, surprisingly,
      Bifidobacterium species were generally positively associated with increased risk
      of colon cancer. Some Lactobacillus species and Eubacterium aerofaciens, which
      also produces major amounts of lactic acid, showed closest associations with low
      risk of colon cancer.

PMID- 7574629
TI  - Stereoselective production of (+)-trans-chrysanthemic acid by a microbial
      esterase: cloning, nucleotide sequence, and overexpression of the esterase gene
      of Arthrobacter globiformis in Escherichia coli.
AB  - The gene coding for a novel esterase which stereoselectively hydrolyzes the (+)
      trans (1R,3R) stereoisomer of ethyl chrysanthemate was cloned from Arthrobacter
      globiformis SC-6-98-28 and overexpressed in Escherichia coli. The cellular
      content of the active enzyme reached 33% of the total soluble protein in the
      recombinant E. coli JM105 cells and 5.6 g/liter of culture by high-density cell
      cultivation. The hydrolytic activity of the recombinant E. coli cells for ethyl
      chrysanthemate reached 605 mumol of chrysanthemic acid per min per g of dry
      cells, which is approximately 2,500-fold higher than that of A. globiformis
      cells. The stereoselective hydrolysis by the recombinant E. coli cells was
      efficient at substrate concentrations of up to 40% by removing the produced
      chrysanthemic acid by ultrafiltration. The (+)-trans-chrysanthemic acid produced
      had 100% optical purity. The amino acid sequence of the esterase was found to be
      similar to that of several class C beta-lactamases, D,D-carboxypeptidase, D
      aminopeptidase, 6-aminohexanoate-dimer hydrolase, and Pseudomonas esterase. The
      sequence comparison also suggested that the Ser-X-X-Lys motif in the esterase was
      at the active site of the enzyme.

PMID- 7574630
TI  - Degradation of iprodione by a soil Arthrobacter-like strain.
AB  - A bacterial strain able to transform iprodione was isolated from a fast iprodione
      degrading soil by enrichment procedures. Transformation was detected through 3,5
      dichloroaniline production as measured by a rapid colorimetric method. The
      strain, MA6, was tentatively identified as an Arthrobacter sp. When it was
      incubated with MA6 in a minimum mineral medium (pH 6.5), iprodione (8.8
      mumol/liter) was transformed into two major metabolites that were identified by
      high-performance liquid chromatography analysis: 3,5-dichlorophenylcarboximide
      (metabolite 1) and (3,5-dichlorophenylurea) acetic acid (metabolite 2), which was
      produced after ring cleavage of the former product. These products were
      synthesized in the laboratory and compared with metabolites 1 and 2 which were
      formed during iprodione degradation. Small quantities of 3,5-dichloroaniline also
      appeared in the bacterial culture but did not substantially increase between the
      first and second days of incubation. In contrast, in the sterile control medium,
      iprodione was spontaneously transformed into hydantoic acid and an iprodione
      isomer. Chemical and biological transformations of iprodione seem to occur
      through two different pathways. One biological degradation pathway is proposed.

PMID- 7574632
TI  - Potential usefulness of bacteriophages that infect Bacteroides fragilis as model
      organisms for monitoring virus removal in drinking water treatment plants.
AB  - The presence of bacteriophages at different stages in three drinking water
      treatment plants was evaluated to study the usefulness of phages as model
      organisms for assessing the efficiency of the processes. The bacteriophages
      tested were somatic coliphages, F-specific coliphages, and phages infecting
      Bacteroides fragilis. The presence of enteroviruses and currently used bacterial
      indicators was also determined. Most bacteriophages were removed during the
      prechlorination-flocculation-sedimentation step. In these particular treatment
      plants, which include prechlorination, phages were, in general, more resistant to
      the treatment processes than present bacterial indicators, with the exception, in
      some cases, of clostridia. Bacteriophages infecting B. fragilis were found to be
      more resistant to water treatment than either somatic or F-specific coliphages or
      even clostridia. Enteric viruses were found only in untreated water in low
      numbers, and consequently, the efficiency of the plants in the removal of viruses
      could not be evaluated with precision. The numbers and frequencies of detection
      of the various microorganisms in water samples taken in the distribution network
      served by the three plants confirm the results found in the finished water at the
      plants.

PMID- 7574631
TI  - Phylogenetic comparison of two polycyclic aromatic hydrocarbon-degrading
      mycobacteria.
AB  - Two mycobacterial strains previously isolated from fossil-fuel-contaminated
      environments and shown to degrade four- and/or five-ring polycyclic aromatic
      hydrocarbons were further characterized. The two strains, PYR-I and RJGII-135,
      had similar growth characteristics, colony morphologies, and scotochromogenic
      pigmentations. DNA amplification fingerprints obtained with total genomic DNA
      indicated some strain similarities but with several distinctly different bands.
      Moreover, phylogenetic analysis based upon essentially full-length 16S rRNA gene
      sequences separates the two strains as distinct species within the fast-growing
      group of mycobacteria. Although both strains are thermosensitive, strain PYR-I
      has the bulged U between positions 184 and 193 characteristic of thermotolerant
      mycobacteria. Both strains are of potential use for reintroduction into and
      bioremediation of polycyclic aromatic hydrocarbon-contaminated soils.

PMID- 7574634
TI  - Growth, induction, and substrate specificity of dehydroabietic acid-degrading
      bacteria isolated from a kraft mill effluent enrichment.
AB  - We investigated resin acid degradation in five bacteria isolated from a bleach
      kraft mill effluent enrichment. All of the bacteria grew on dehydroabietic acid
      (DHA), a resin acid routinely detected in pulping effluents, or glycerol as the
      sole carbon source. None of the strains grew on acetate or methanol. Glycerol
      grown, high-density, resting-cell suspensions were found to undergo a lag for 2
      to 4 h before DHA degradation commenced, suggesting that this activity was
      inducible. This was further investigated by spiking similar cultures with
      tetracycline, a protein synthesis inhibitor, at various times during the DHA
      disappearance curve. Cultures to which the antibiotic was added prior to the lag
      did not degrade DHA. Those that were spiked with the antibiotic after the lag
      phase (4 h) degraded DHA at the same rate as did controls with no added
      tetracycline. Therefore, de novo protein synthesis was required for DHA
      biodegradation, confirming that this activity is inducible. The five strains were
      also evaluated for their ability to degrade other resin acids. All strains
      behaved in a similar fashion. Unchlorinated abietane-type resin acids (abietic
      acid, DHA, and 7-oxo-DHA) were completely degraded within 7 days, whereas
      pimarane resin acids (sandaracopimaric acid, isopimaric acid, and pimaric acid)
      were poorly degraded (25% or less). Chlorination of DHA affected biodegradation,
      with both 12,14-dichloro-DHA and 14-chloro-DHA showing resistance to degradation.
      However, 50 to 60% of the 12-chloro-DHA was consumed within the same period.

PMID- 7574633
TI  - Alasan, a new bioemulsifier from Acinetobacter radioresistens.
AB  - Acinetobacter radioresistens KA53, isolated by enrichment culture, was found to
      produce an extracellular, nondialyzable emulsifying agent (referred to as alasan)
      when grown on ethanol medium in a batch-fed reactor. The crude emulsifier was
      concentrated from the cell-free culture fluid by ammonium sulfate precipitation
      to yield 2.2 g of emulsifier per liter. Alasan stabilized a variety of oil-in
      water emulsions, including n-alkanes with chain lengths of 10 or higher, alkyl
      aromatics, liquid paraffin, soybean and coconut oils, and crude oil. Alasan was
      2.5 to 3.0 times more active after being heated at 100 degrees C under neutral or
      alkaline conditions. Emulsifying activity was observed over the entire pH range
      studied (pH 3.3 to 9.2), with a clear maximum at pH 5.0. Magnesium ions
      stimulated the activity both below (pH 3.3 to 4.5) and above (pH 5.5 to 9.3) the
      pH optimum. Alasan activity was higher in 20 mM citrate than in 20 mM acetate or
      Tris-HCl buffer. Preliminary chemical characterization of alasan indicated that
      it is a complex of an anionic, high-molecular-weight, alanine-containing
      heteropolysaccharide and protein.

PMID- 7574635
TI  - Aqueous two-phase polymer systems as tools for the study of a recombinant surface
      expressed Escherichia coli hemagglutinin.
AB  - The surface expression of an integral membrane hemagglutinin, HRA1, cloned from
      Escherichia coli O9: H10:K99 in heterologous E. coli strains was studied by
      utilizing a variety of polyethylene glycol-dextran and dextran-Ficoll aqueous two
      phase polymer systems. Bacteria containing plasmids that encoded the
      hemagglutinin were found to partition differently from both the host bacteria
      lacking the plasmid and the original hemagglutinating strain in several of these
      systems. By using molecular biological techniques, the origin of the partition
      difference was unambiguously correlated to the expression of HRA1, providing
      evidence independent of the agglutination phenotype that the protein was
      accessible to the surrounding milieu. It was demonstrated by using bacterial
      partition in charge-sensitive systems that the agglutination event was not likely
      to be due to the presence of a nonspecific positively charged surface protein, as
      HRA1-expressing clones showed no less affinity for the relatively positive
      polyethylene glycol-rich upper phase than did control bacteria. This work
      demonstrates the utility of aqueous polymer two-phase systems for the study of
      surface-expressed recombinant proteins, due to the sensitivity of the systems and
      the presence of excellent controls (the host bacteria before plasmid
      introduction). In cloning and expression studies of surface-associated proteins,
      two-phase aqueous polymer systems could be used as an alternative to antibody
      production for the monitoring of surface expression, and these systems may give
      valuable information on the surface exposure of the protein.

PMID- 7574636
TI  - Development of a microbial community of bacterial and yeast antagonists to
      control wound-invading postharvest pathogens of fruits.
AB  - Two antagonists, the bacterium Pseudomonas syringae and the pink yeast
      Sporobolomyces roseus, against blue mold (caused by Penicillium expansum) on
      apple controlled this disease more effectively when combined at approximately
      equal biomass (50:50 of the same turbidity) than in individual applications.
      Addition of L-asparagine enhanced the biocontrol effectiveness of P. syringae but
      decreased that of S. roseus and had no significant effect when the antagonists
      were combined. Populations of both antagonists increased in apple wounds and were
      further stimulated by the addition of L-asparagine. The carrying capacity of
      wounds for P. syringae was not affected by S. roseus. Populations of P. syringae
      in wounds inoculated individually or in a 50:50 mixture with S. roseus reached
      the same level after 3 days at 22 degrees C. However, populations of S. roseus
      recovered after applications of the mixture were consistently lower than those
      recovered after individual applications. Similar effects were observed in in
      vitro tests in which populations of S. roseus grown in mixtures with P. syringae
      were consistently lower than those grown alone, while the populations of P.
      syringae were not affected by the presence of S. roseus. A total of 36 carbon and
      35 nitrogen compounds were tested for utilization by both antagonists. Fourteen
      nitrogenous compounds were utilized by both P. syringae and S. roseus, and an
      additional nine compounds were utilized by P. syringae. S. roseus and P. syringae
      utilized 17 and 13 carbon sources, respectively; 9 sources were common to both
      antagonists. Populations of these antagonists in apple wounds appear to form a
      relatively stable community dominated by P. syringae.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7574637
TI  - Suitability of selective plating media for recovering heat- or freeze-stressed
      Escherichia coli O157:H7 from tryptic soy broth and ground beef.
AB  - The efficacy of tryptic soy agar (TSA), modified sorbitol MacConkey agar (MSMA),
      modified eosin methylene blue (MEMB) agar, and modified SD-39 (MSD) agar in
      recovering a five-strain mixture of enterohemorrhagic Escherichia coli O157:H7
      and five non-O157 strains of E. coli heated in tryptic soy broth at 52, 54, or 56
      degrees C for 10, 20, and 30 min was determined. Nonselective TSA supported the
      highest recovery of heated cells. Significantly (P < or = 0.05) lower recovery of
      heat-stressed cells was observed on MSMA than on TSA, MEMB agar, or MSD agar. The
      suitability of MEMB agar or MSD agar for recovery of E. coli O157:H7 from heated
      or frozen (-20 degrees C) low- or high-fat ground beef was determined. Recovery
      of E. coli O157:H7 from heated ground beef was significantly (P < or = 0.05)
      higher on TSA than on MEMB agar, which in turn supported higher recovery than MSD
      agar did; MSMA was inferior. Recovery from frozen ground beef was also higher on
      MEMB and MSD agars than on MSMA. Higher populations were generally recovered from
      high-fat beef than from low-fat beef, but the relative performance of the
      recovery media was the same. The inability of MSMA to recover stressed cells of
      E. coli O157:H7 underscores the need to develop a better selective medium for
      enumerating E. coli O157:H7.

PMID- 7574638
TI  - 2,4-Dichlorophenoxyacetic acid-degrading bacteria contain mosaics of catabolic
      genes.
AB  - DNA from 32 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacteria from
      diverse locations was probed with the first three genes of the well-known 2,4-D
      degradation pathway found in Alcaligenes eutrophus JMP134(pJP4). The majority of
      strains did not show high levels of homology to the first three genes of the 2,4
      D degradation pathway, tfdA, -B, and -C. Most strains showed combinations of tfdA
      , B-, and C-like elements that exhibited various degrees of homology to the gene
      probes. Strains having the same genomic fingerprints (as determined by repetitive
      extragenic palindromic PCR) exhibited the same hybridization pattern regardless
      of the geographic origin of the strain, with the exception of a strain isolated
      from Puerto Rico. This strain had the same genomic fingerprint as that of
      numerous other strains in the collection but differed in its hybridization
      against the tfdA gene probe. Members of the beta subdivision of the
      Proteobacteria class, specifically Alcaligenes, Burkholderia, and Rhodoferax
      species, carried DNA fragments with 60% or more sequence similarity to tfdA of
      pJP4, and most carried fragments showing at least 60% homology to tfdB. However,
      many strains did not hybridize with tfdC, although they exhibited chlorocatechol
      dioxygenase activity. Members of the alpha subdivision of the Proteobacteria
      class, mostly of the genus Sphingomonas, did not hybridize to either tfdA or
      tfdC, but some hybridized at low stringency to tfdB. The data suggest that
      extensive interspecies transfer of a variety of homologous degradative genes has
      been involved in the evolution of 2,4-D-degrading bacteria.

PMID- 7574639
TI  - The cellular location of Prevotella ruminicola beta-1,4-D-endoglucanase and its
      occurrence in other strains of ruminal bacteria.
AB  - Prevotella ruminicola B(1)4, TC1-1, TF1-3, and TS1-5 all produced immunologically
      cross-reacting 88- and 82-kDa carboxymethyl cellulases (CMCases). P. ruminicola
      23, 118B, 20-63, and 20-78 had much lower CMCase activities, and Western blots
      (immunoblots) showed no cross-reaction with the B(1)4 CMCase antiserum.
      Fibrobacter succinogenes S85 and Selenomonas ruminantium HD4 and D produced
      CMCase, but these enzymes were smaller and did not cross-react with the B(1)4
      CMCase antiserum. The B(1)4 CMCase antiserum inhibited the B(1)4, TC1-1, TF1-3,
      and TS1-5 CMCase activities and agglutinated these cells, but it had no effect on
      the other strains or species. On the basis of these results, the B(1)4 CMCase is
      a strain-specific enzyme that is located on the outside surface of the cells. P.
      ruminicola B(1)4 cultures, grown on sucrose, did not have significant CMCase
      activity, but these cells could bind purified 88- and 82-kDa CMCase but not 40.5
      kDa CMCase. Because the 40.5-kDa CMCase is a fully active, truncated form of the
      CMCase, it appears that the N-terminal domain of the 88-kDa B(1)4 CMCase anchors
      the CMCase to the cells. Cells grown on cellobiose produced at least 10-fold more
      CMCase than the sucrose-grown cells, and the cellobiose-grown cells could only
      bind 15% as much CMCase as sucrose-grown cells. Virtually all of the CMCase
      activity of exponentially growing cultures was cell associated, but CMCase
      activity was eventually detected in the culture supernatant. On the basis of the
      observation that the 88-kDa CMCase was gradually converted to the 82-kDa CMCase
      when cultures reached the stationary phase without a change in specific activity,
      it appears that the 82-kDa protein is probably a proteolytic degradation product
      of the 88-kDa CMCase.

PMID- 7574640
TI  - Isolation and characterization of an anaerobic ruminal bacterium capable of
      degrading hydrolyzable tannins.
AB  - An anaerobic diplococcoid bacterium able to degrade hydrolyzable tannins was
      isolated from the ruminal fluid of a goat fed desmodium (Desmodium ovalifolium),
      a tropical legume which contains levels as high as 17% condensed tannins. This
      strain grew under anaerobic conditions in the presence of up to 30 g of tannic
      acid per liter and tolerated a range of phenolic monomers, including gallic,
      ferulic, and p-coumaric acids. The predominant fermentation product from tannic
      acid breakdown was pyrogallol, as detected by high-performance liquid
      chromatography and mass spectrometry. Tannic acid degradation was dependent on
      the presence of a sugar such as glucose, fructose, arabinose, sucrose, galactose,
      cellobiose, or soluble starch as an added carbon and energy source. The strain
      also demonstrated resistance to condensed tannins up to a level of 4 g/liter.

PMID- 7574641
TI  - Cloning of an Azorhizobium caulinodans endoglucanase gene and analysis of its
      role in symbiosis.
AB  - Azorhizobium caulinodans ORS571, a symbiont of the tropical leguminous plant
      Sesbania rostrata, showed low, constitutive levels of endoglucanase (Egl)
      activity. A clone carrying the gene responsible for this phenotype was isolated
      via introduction of a genomic library into the wild-type strain and screening for
      transconjugants with enhanced Egl activity. By subcloning and expression in
      Escherichia coli, the Egl phenotype was allocated to a 3-kb EcoRI-BamHI fragment.
      However, sequence analysis showed the egl gene to be much larger, consisting of
      an open reading frame of 1,836 amino acids. Within the deduced polypeptide, three
      kinds of putative domains were identified: a catalytic domain, two cellulose
      binding domains, and an eightfold reiterated motif. The catalytic domain belongs
      to the family A of cellulases. A C-terminal stretch of 100 amino acids was
      similar to family II cellulose-binding domains. A second copy of this domain
      occurred near the middle of the polypeptide, flanked by reiterated motifs. ORS571
      mutants carrying a Tn5 insertion in the egl gene had lost the Egl activity. These
      mutants as well as Egl-overproducing strains showed a normal nodulation behavior,
      indistinguishable from wild-type nodulation on Sesbania rostrata under laboratory
      conditions.

PMID- 7574642
TI  - Isolation and characterization of polygalacturonase genes (pecA and pecB) from
      Aspergillus flavus.
AB  - Two genes, pecA and pecB, encoding endopolyglacturonases were cloned from a
      highly aggressive strain of Aspergillus flavus. The pecA gene consisted of 1,228
      bp encoding a protein of 363 amino acids with a predicted molecular mass of 37.6
      kDa, interrupted by two introns of 58 and 81 bp in length. Accumulation of pecA
      mRNA in both pectin- or glucose-grown mycelia in the highly aggressive strain
      matched the activity profile of a pectinase previously identified as P2c.
      Transformants of a weakly aggressive strain containing a functional copy of the
      pecA gene produced P2c in vitro, confirming that pecA encodes P2c. The coding
      region of pecB was determined to be 1,217 bp in length interrupted by two introns
      of 65 and 54 bp in length. The predicted protein of 366 amino acids had an
      estimated molecular mass of 38 kDa. Transcripts of this gene accumulated in
      mycelia grown in medium containing pectin alone, never in mycelia grown in
      glucose-containing medium, for both highly and weakly aggressive strains. Thus,
      pecB encodes the activity previously identified as P1 or P3. pecA and pecB share
      a high degree of sequence identity with polygalacturonase genes from Aspergillus
      parasiticus and Aspergillus oryzae, further establishing the close relationships
      between members of the A. flavus group. Conservation of intron positions in these
      genes also indicates that they share a common ancestor with genes encoding
      endopolyglacturonases of Aspergillus niger.

PMID- 7574645
TI  - Microscale detection of specific bacterial DNA in soil with a magnetic capture
      hybridization and PCR amplification assay.
AB  - A magnetic capture-hybridization PCR technique (MCH-PCR) was developed to
      eliminate the inhibitory effect of humic acids and other contaminants in PCRs
      targeting specific soil DNA. A single-stranded DNA probe, which was complementary
      to an internal part of the target gene, was used to coat magnetic beads. After
      hybridization in a suspension of soil DNA, magnetic extraction of the beads
      separated the hybrid DNA from all other soil DNA, humic acids, and other
      interfering soil components. The MCH was followed by PCR amplification of the
      specific target DNA. In barley rhizosphere soil, detection of a lux gene inserted
      in a Pseudomonas fluorescens strain could be demonstrated in nonsterile soil
      samples (0.5 mg). This corresponded to a detection of fewer than 40 bacterial
      cells per cm of barley root. The MCH-PCR technique greatly improves the current
      protocols for PCR detection of specific microorganisms or genes in soil because
      specific target DNA sequences from very small soil samples can be extracted and
      determined.

PMID- 7574643
TI  - Use of starvation promoters to limit growth and selectively enrich expression of
      trichloroethylene- and phenol-transforming activity in recombinant Escherichia
      coli [corrected].
AB  - The expression of much useful bacterial activity is facilitated by rapid growth.
      This coupling can create problems in bacterial fermentations and in situ
      bioremediation. In the latter process, for example, it necessitates addition of
      large amounts of nutrients to contaminated environments, such as aquifers. This
      approach, termed biostimulation, can be technically difficult. Moreover, the
      resulting in situ bacterial biomass production can have undesirable consequences.
      In an attempt to minimize coupling between expression of biodegradative activity
      and growth, we used Escherichia coli starvation promoters to control toluene
      monooxygenase synthesis. This enzyme complex can degrade the environmental
      contaminants trichloroethylene (TCE) and phenol. Totally starving cell
      suspensions of such strains degraded phenol and TCE. Furthermore, rapid
      conversions occurred in the postexponential batch or very slow growth (dilution)
      rate chemostat cultures, and the nutrient demand and biomass formation for
      transforming a given amount of TCE or phenol were reduced by 60 to 90%. Strong
      starvation promoters have recently been clones and characterized in
      environmentally relevant bacteria like Pseudomonas species; thus, starvation
      promoter-driven degradative systems can now be constructed in such bacteria and
      tested for in situ efficacy.

PMID- 7574644
TI  - Nucleotide sequence analysis of genes encoding a toluene/benzene-2-monooxygenase
      from Pseudomonas sp. strain JS150.
AB  - It was previously shown by others that Pseudomonas sp. strain JS150 metabolizes
      benzene and alkyl- and chloro-substituted benzenes by using dioxygenase-initiated
      pathways coupled with multiple downstream metabolic pathways to accommodate
      catechol metabolism. By cloning genes encoding benzene-degradative enzymes, we
      found that strain JS150 also carries genes for a toluene/benzene-2-monooxygenase.
      The gene cluster encoding a 2-monooxygenase and its cognate regulator was cloned
      from a plasmid carried by strain JS150. Oxygen (18O2) incorporation experiments
      using Pseudomonas aeruginosa strains that carried the cloned genes confirmed that
      toluene hydroxylation was catalyzed through an authentic monooxygenase reaction
      to yield ortho-cresol. Regions encoding the toluene-2-monooxygenase and
      regulatory gene product were localized in two regions of the cloned fragment. The
      nucleotide sequence of the toluene/benzene-2-monooxygenase locus was determined.
      Analysis of this sequence revealed six open reading frames that were then
      designated tbmA, tbmB, tbmC, tbmD, tbmE, and tbmF. The deduced amino acid
      sequences for these genes showed the presence of motifs similar to well-conserved
      functional domains of multicomponent oxygenases. This analysis allowed the
      tentative identification of two terminal oxygenase subunits (TbmB and TbmD) and
      an electron transport protein (TbmF) for the monooxygenase enzyme. In addition to
      these gene products, all the tbm polypeptides shared significant homology with
      protein components from other bacterial multicomponent monooxygenases. Overall,
      the tbm gene products shared greater similarity with polypeptides from the phenol
      hydroxylases of Pseudomonas putida CF600, P35X, and BH than with those from the
      toluene monooxygenases of Pseudomonas mendocina KR1 and Burkholderia
      (Pseudomonas) pickettii PKO1. The relationship found between the phenol
      hydroxylases and a toluene-2-monooxygenase, characterized in this study for the
      first time at the nucleotide sequence level, suggested that DNA probes used for
      surveys of environmental populations should be carefully selected to reflect DNA
      sequences corresponding to the metabolic pathway of interest.

PMID- 7574646
TI  - Cloning, characterization, and expression of a gene region from Pseudomonas sp.
      strain ADP involved in the dechlorination of atrazine.
AB  - We previously identified a Pseudomonas sp. strain, ADP, which rapidly metabolized
      atrazine in liquid culture, agar plates, and soils (R. T. Mandelbaum, D. L.
      Allan, L. P. Wackett, Appl. Environ. Microbiol. 61:1451-1457, 1995). In this
      study, we report the cloning and partial characterization of a gene region from
      Pseudomonas sp. strain ADP that encodes atrazine degradation activity. A 22-kb
      EcoRI genomic DNA fragment, designated pMD1, was shown to encode atrazine
      dechlorination activity in Escherichia coli DH5 alpha. Atrazine degradation was
      demonstrated by a zone-clearing assay on agar medium containing crystalline
      atrazine and by chromatographic methods. A gene conferring the atrazine-clearing
      phenotype was subsequently subcloned as a 1.9-kb AvaI fragment in pACYC184,
      designated pMD4, and was expressed in E. coli. This result and random Tn5
      mutagenesis established that the 1.9-kb AvaI fragment was essential for atrazine
      dechlorination. High-pressure liquid and thin-layer chromatographic analyses were
      used to rigorously establish that E. coli containing pMD4 degraded atrazine and
      accumulated hydroxyatrazine. Hydroxyatrazine was detected only transiently in E.
      coli containing pMD1. This is consistent with the idea that hydroxyatrazine is
      the first metabolite in atrazine degradation by Pseudomonas sp. strain ADP. A 0.6
      kb ApaI-PstI fragment from pMD4, containing the putative atrazine chlorohydrolase
      gene, hybridized to DNA from atrazine-degrading bacteria isolated in Switzerland
      and Louisiana.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7574647
TI  - Oxidative metabolism in nonculturable Helicobacter pylori and Vibrio vulnificus
      cells studied by substrate-enhanced tetrazolium reduction and digital image
      processing.
AB  - Growing and nonculturable cells of Helicobacter pylori and Vibrio vulnificus were
      studied for the capacity to reduce tetrazolium salts in order to elucidate the
      possible physiological basis for the proposed "viable but nonculturable" (VNC)
      state. Initial difficulties in obtaining consistent reduction of rho
      iodonitrotetrazolium violet (INT) by H. pylori led us to develop a method for
      studying the effect of adding exogenous substrates on these reactions. The
      established procedure provided a profile of substrate enhancement of oxidative
      activity revealed by INT reduction which was related to both the identity and
      physiological state of the organism studied. Representation and interpretation of
      these enhancement profiles were facilitated by digital image processing.
      Nonculturable cells of H. pylori produced by carbon and nitrogen starvation in
      air lost all INT-reducing capacity in 24 h when stored at 37 degrees C, while 99%
      of those produced at 4 degrees C retained oxidative activity for at least 250
      days when tested in the presence but not in the absence of succinate, alpha
      ketoglutarate, or aspartate. Activity was detected at similar levels in cells
      with coccoid and spiral shapes. In contrast, only 1% of nonculturable cells of V.
      vulnificus, produced under conditions previously reported to induce the VNC state
      in this organism, retained intrinsic INT-reducing capacity; no substrate-enhanced
      activity occurred in the remainder of the population. Thus, there was no common
      pattern of oxidative activity indicative of a VNC state in both test organisms.
      Nonculturable cells of H. pylori can retain several different oxidative enzyme
      activities; whether these indicate viability or the persistence of cells as "bags
      of enzymes" remains to be established.

PMID- 7574648
TI  - Mechanism of pyrithione-induced membrane depolarization in Neurospora crassa.
AB  - Pyrithione is a general inhibitor of membrane transport in fungi and is widely
      used in antidandruff shampoos as an antifungal agent. An electrophysiological
      approach has been used to determine the mode of action of pyrithione on the
      plasma membrane of the model ascomycete, Neurospora crassa. At pH 5.8, pyrithione
      induces a dramatic dose-dependent electrical depolarization of the membrane which
      is complete within 4 min, amounts to 110 mV at saturating pyrithione
      concentrations, and is half maximal between 0.6 and 0.8 mM pyrithione. Zinc
      pyrithione induces a similar response but exerts a half-maximal effect at around
      0.3 mM. The depolarization is strongly dependent on external pH, being almost
      absent at pH 8.2, at which the concentration of the uncharged form of pyrithione-
      which might be expected to permeate the membrane freely--is markedly lowered.
      However, quantitative considerations based on cytosolic buffer capacity, the pKa
      of pyrithione, and the submillimolar concentration at which it is active appear
      to preclude significant cytosolic acidification on dissociation of the thiol
      proton from the uncharged form of pyrithione. Current-voltage analysis
      demonstrates that the depolarization is accompanied by a decrease in membrane
      electrical conductance in a manner consistent with inhibition of the primary
      proton pump and inconsistent with a mode of action of pyrithione on plasma
      membrane ion channels. We conclude that pyrithione inhibits membrane transport
      via a direct or indirect effect on the primary proton pump which energizes
      transport and that the site of action of pyrithione is likely to be intra- rather
      than extracellular.

PMID- 7574649
TI  - New polymeric model substrates for the study of microbial ligninolysis.
AB  - Lignin model dimers are valuable tools for the elucidation of microbial
      ligninolytic mechanisms, but their low molecular weight (MW) makes them
      susceptible to nonligninolytic intracellular metabolism. To address this problem,
      we prepared lignin models in which unlabeled and alpha-14C-labeled beta-O-4
      linked dimers were covalently attached to 8,000-MW polyethylene glycol (PEG) or
      to 45,000-MW polystyrene (PS). The water-soluble PEG-linked model was mineralized
      extensively in liquid medium and in solid wood cultures by the white rot fungus
      Phanerochaete chrysosporium, whereas the water-insoluble PS-linked model was not.
      Gel permeation chromatography showed that P. chrysosporium degraded the PEG
      linked model by cleaving its lignin dimer substructure rather than its PEG
      moiety. C alpha-C beta cleavage was the major fate of the PEG-linked model after
      incubation with P. chrysosporium in vivo and also after oxidation with P.
      chrysosporium lignin peroxidase in vitro. The brown rot fungus Gloeophyllum
      trabeum, which unlike P. chrysosporium lacks a vigorous extracellular
      ligninolytic system, was unable to degrade the PEG-linked model efficiently.
      These results show that PEG-linked lignin models are a marked improvement over
      the low-MW models that have been used in the past.

PMID- 7574650
TI  - Cloning of nod gene regions from mesquite rhizobia and bradyrhizobia and
      nucleotide sequence of the nodD gene from mesquite rhizobia.
AB  - Nitrogen-fixing symbiosis between bacteria and the tree legume mesquite (Prosopis
      glandulosa) is important for the maintenance of many desert ecosystems. Genes
      essential for nodulation and for extending the host range to mesquite were
      isolated from cosmid libraries of Rhizobium (mesquite) sp. strain HW17b and
      Bradyrhizobium (mesquite) sp. strain HW10h and were shown to be closely linked.
      All of the cosmid clones of rhizobia that extended the host range of Rhizobium
      (Parasponia) sp. strain NGR234CS to mesquite also supported nodulation of a Sym-
      mesquite strain. The cosmid clones of bradyrhizobia that extended the host range
      of Rhizobium (Parasponia) sp. strain NGR234CS to mesquite were only able to
      confer nodulation ability in the Sym- mesquite strain if they also contained a
      nodD-hybridizing region. Subclones containing just the nodD genes of either genus
      did not extend the host range of Rhizobium (Parasponia) sp. to mesquite,
      indicating that the nodD gene is insufficient for mesquite nodulation. The nodD
      gene region is conserved among mesquite-nodulating rhizobia regardless of the
      soil depth from which they were collected, indicating descent from a common
      ancestor. In a tree of distance relationships, the NodD amino acid sequence from
      mesquite rhizobia clusters with homologs from symbionts that can infect both
      herbaceous and tree legumes, including Rhizobium tropici, Rhizobium leguminosarum
      bv; phaseoli, Rhizobium loti, and Bradyrhizobium japonicum.

PMID- 7574651
TI  - Application of antisera raised against sulfate-reducing bacteria for indirect
      immunofluorescent detection of immunoreactive bacteria in sediment from the
      German Baltic Sea.
AB  - Polyclonal rabbit antisera raised against sulfate-reducing bacteria (SRB) could
      detect several distinct populations of bacteria in sediment from the German
      Baltic Sea. The depth distribution of immunoreactive bacteria was determined by
      an indirect immunofluorescence filter method. Anti-Desulfovibrio desulfuricans
      DSM 1926 serum showed maximum bacterial numbers at a depth of 18 cm, with a
      concentration of 60 x 10(6) cells cm-3. With anti-Desulfovibrio baculatus DSM
      2555 serum, counts were highest at the same depth, approaching 0.7 x 10(6) cells
      cm-3. Other significantly smaller populations were observed. Anti-SRBStrain 1
      (lactate,vibrio) maxima were at 0 to 4 cm and at 17 to 18 cm. Anti-SRBStrain 2
      (lactate,vibrio) serum showed several local maxima. Anti-SRBStrain 3
      (lactate,oval) serum detected one single peak at a depth of 10 to 12 cm. Also
      determined were rates of sulfate reduction, total bacterial counts by acridine
      orange staining, and the viable counts by dilution series on anaerobic lactate
      medium. The total bacterial counts were highest (180 x 10(6) cells cm-3) at 3 to
      4 cm and dropped to 24 x 10(6) cells cm-3 at 10 to 11 cm but showed additional
      local maxima reaching 140 x 10(6) cells cm-3 at a depth of 17 to 18 cm. Viable
      counts probable number) were above 10(5) CFU cm-3 at 0 to 3.6 cm but remained
      below 10(3) CFU at 7.2 to 18 cm. The sulfate reduction rate was maximal (107 nmol
      cm-3 day-1) at a depth of 1 to 2 cm, dropped to 10 nmol cm-3 day-1 at 12 to 13
      cm, and reached 38 nmol cm-3 day-1 at 17 to 18 cm.

PMID- 7574652
TI  - Genotyping of rotaviruses isolated from sewage.
AB  - Rotaviruses from environmental samples have been genotyped by a seminested
      reverse transcription PCR assay with serotype-specific primers derived from
      variable regions of gene 9, which produce different characteristic segment sizes
      for serotypes 1 to 4. The method enabled the detection and identification of type
      1, 2, and 3 group A rotaviruses in sewage.

PMID- 7574653
TI  - Use of bioluminescence to model the thermal inactivation of Salmonella
      typhimurium in the presence of a competitive microflora.
AB  - The survival of Salmonella typhimurium was investigated by bioluminescence and
      standard plating techniques in pure cultures and in the presence of competitors
      after the cultures were heated to 55 degrees C for increasing lengths of time.
      Decimal reduction (D) values increased from 0.43 to 2.09 min in the presence of
      10(8) CFU of competitors ml-1, indicating a significant protective effect.

PMID- 7574654
TI  - In vitro H2 utilization by a ruminal acetogenic bacterium cultivated alone or in
      association with an archaea methanogen is stimulated by a probiotic strain of
      Saccharomyces cerevisiae.
AB  - The effects of a live strain of Saccharomyces cerevisiae on hydrogen utilization
      and acetate and methane production by two hydrogenotrophic ruminal
      microorganisms, an acetogenic bacterial strain and an archaea methanogen, were
      investigated. The addition of yeast cells enhanced by more than fivefold the
      hydrogenotrophic metabolism of the acetogenic strain and its acetate production.
      In the absence of yeasts, and in a coculture of the acetogen and the methanogen,
      hydrogen was principally used for methane synthesis, but the presence of live
      yeast cells stimulated the utilization of hydrogen by the acetogenic strain and
      enhanced acetogenesis.

PMID- 7574655
TI  - Reexamination of tetrodotoxin production by bacteria.
AB  - Vibrio alginolyticus has been reported as a good producer of tetrodotoxin (TTX),
      but the toxin extracted from this bacterium did not react to the monoclonal
      antibody against TTX. Surprisingly, chromatographic analyses detected high TTX
      peaks for polypeptone and yeast extracts used as medium materials, which were, as
      expected, all negative by the mouse bioassay. These results may require us to
      revise the bacterial production of TTX.

PMID- 7574657
TI  - Nested PCR method for rapid and sensitive detection of Vibrio vulnificus in fish,
      sediments, and water.
AB  - A nested PCR for the detection of Vibrio vulnificus in fish farms was developed
      as an alternative to cultural methods by using universal primers flanking the V.
      vulnificus-specific sequences directed against 23S rRNA genes. This specific
      assay detected 10 fg of DNA or 12 to 120 cells in artificially inoculated samples
      without enrichment and within 24 h.

PMID- 7574658
TI  - Induction of toluene oxidation activity in Pseudomonas mendocina KR1 and
      Pseudomonas sp. strain ENVPC5 by chlorinated solvents and alkanes.
AB  - Toluene oxidation activity in Pseudomonas mendocina KR1 and Pseudomonas sp.
      strain ENVPC5 was induced by trichloroethylene (TCE), and induction was followed
      by the degradation of TCE. Higher levels of toluene oxidation activity were
      achieved in the presence of a supplemental growth substrate such as glutamate,
      with levels of activity of up to 86% of that observed with toluene-induced cells.
      Activity in P. mendocina KR1 was also induced by cis-1,2-dichloroethylene,
      perchloroethylene, chloroethane, hexane, pentane, and octane, but not by trans
      1,2-dichloroethylene. Toluene oxidation was not induced by TCE in Burkholderia
      (Pseudomonas) cepacia G4, P. putida F1, Pseudomonas sp. strain ENV110, or
      Pseudomonas sp. strain ENV113.

PMID- 7574656
TI  - Efficacy of ozonated water against various food-related microorganisms.
AB  - The antimicrobial effects of ozonated water in a recirculating concurrent reactor
      were evaluated against four gram-positive and four gram-negative bacteria, two
      yeasts, and spores of Aspergillus niger. More than 5 log units each of Salmonella
      typhimurium and Escherichia coli cells were killed instantaneously in ozonated
      water with or without addition of 20 ppm of soluble starch (SS). In ozonated
      water, death rates among the gram-negative bacteria--S. typhimurium, E. coli,
      Pseudomonas aeruginosa, and Yersinia enterocolitica--were not significantly
      different (P > 0.05). Among gram-positive bacteria, Listeria monocytogenes was
      significantly P < 0.05) more sensitive than either Staphylococcus aureus or
      Enterococcus faecalis. In the presence of organic material, death rates of S.
      aureus compared with L. monocytogenes and E. coli compared with S. typhimurium in
      ozonated water were not significantly (P > 0.05) affected by SS addition but were
      significantly reduced (P < 0.05) by addition of 20 ppm of bovine serum albumin
      (BSA). More than 4.5 log units each of Candida albicans and Zygosaccharomyces
      bailii cells were killed instantaneously in ozonated water, whereas less than 1
      log unit of Aspergillus niger spores was killed after a 5-min exposure. The
      average ozone output levels in the deionized water (0.188 mg/ml) or water with SS
      (0.198 mg/ml) did not differ significantly (P < 0.05) but were significantly
      lower in water containing BSA (0.149 mg/ml).

PMID- 7574659
TI  - Morphological variation of new Thermoplasma acidophilum isolates from Japanese
      hot springs.
AB  - We isolated 12 strains of Thermoplasma acidophilum from hot springs in Hakone,
      Japan. T. acidophilum strains showed morphological variation in the crystal-like
      structure in the cell and the fibrous structure on the cell surface. Two strains
      tested were sensitive to novobiocin. However, a novobiocin-resistant mutant was
      obtained by spontaneous mutation.

PMID- 7574660
TI  - Biodiversity of gas vacuolate bacteria from Antarctic sea ice and water.
AB  - Psychrophilic, gas vacuolate, heterotrophic bacteria indigenous to sea ice
      communities in Antarctica have been isolated. Phylogenetic analysis of
      representative members of these bacteria shows that they belong to the alpha,
      beta, and gamma Proteobacteria and the Flavobacteria-Cytophaga group. This is the
      first report of gas vacuolate bacteria from the beta Proteobacteria and the
      Flavobacteria-Cytophaga groups.

PMID- 7574662
TI  - Diversity in cyclic nucleotide phosphodiesterase isoenzyme families.

PMID- 7574663
TI  - Isolation and sequencing of two cDNA clones encoding rat spleen cathepsin E and
      analysis of the activation of purified procathepsin E.
AB  - Cathepsin E (CE) is an intracellular, nonlysosomal aspartic proteinase consisting
      of two identical subunits with a molecular mass of approximately 42 kDa and has a
      unique subcellular distribution in various rat tissues. In this study, we
      determined the complete amino acid sequence of rat spleen CE and examined the
      activation mechanism of the proenzyme purified from this tissue. Two cDNA clones
      encoding rat CE, termed pTN05 and pTN1, were isolated. Comparison of the amino
      acid sequences predicted from the respective cDNA sequences revealed that they
      were essentially identical, except that pTN1 lacked a sequence corresponding to
      residues Tyr293-Pro325 of the longer cDNA clone (pTN05). Based on the structural
      analysis of purified enzyme forms, the CE precursor was found to comprise a
      signal peptide, a prosequence, and a mature protein region of 19, 39, and 337
      (pTN05) or 304 (pTN1) residues, respectively. Despite a high degree of similarity
      in the overall structure of CE between rat and other mammalian species, the first
      11 residues in the NH2-terminal sequence of rat mature enzyme were significantly
      different from those of other species. The purified pro-CE was analyzed for its
      conversion to the mature form. The results indicated that the maximal conversion
      occurred at pH 3.0-4.0 in a temperature- and time-dependent manner by
      autocatalytic cleavage at the site between Phe39-Ser40. This conversion was
      highly dependent on the protein concentrations of pro-CE and delayed by the
      presence of exogenous substrates, suggesting the predominance of intermolecular
      reaction for its conversion to the mature form.

PMID- 7574664
TI  - Mapping the intersubunit region of influenza virus hemagglutinin: comparative CD
      and FTIR spectroscopic studies on multiple antigenic peptides.
AB  - An A/PR/8/34 (IHN1) influenza virus hemagglutinin (HA)-specific monoclonal
      antibody (Z38) was found to react with the solid phase adsorbed influenza virus
      expressing uncleaved (HA0) molecules but not to bind to virus particles bearing
      enzymatically cleaved hemagglutinin. Synthetic peptides corresponding to the
      uncleaved HA0 317-341 intersubunit region of subtypes H1-H3 (IP1-IP3) or
      comprising either the C-terminal 317-329 amino acids of HA1 (CP1) or the N
      terminal 330-341 of HA2 (fusion peptide, FP) subunits of cleaved HA were used to
      characterize the fine specificity of Z38 mAb. Circular dichroism and Fourier
      transform infrared spectroscopy showed that, compared to IP2 and IP3 comprising
      the H2 and H3 subtype fragments of the intact intersubunit region, IP1 has
      relatively low helicity but a tendency to adopt beta-turns in trifluoroethanol.
      The immunological and conformational properties of multiple antigenic peptides
      (MAPs) containing four copies of CP1 were also studied. Based on the appearance
      of an infrared component band at 1637 cm-1 (beta-turn band), the CP1 arms of MAPs
      also contain repeats of beta-turns. However, it is only the MAP1-FP construct
      comprising also the fusion peptide, which binds Z38 mAb as strongly as IP1 does.
      This puts emphasis on the role of the fusion region in modifying conformation and
      consequently the ability of peptides to elicit an antibody response. The results
      obtained for peptide conformation also suggests a beta-turn(s)/beta-sheet/beta
      turn/beta-sheet conformational motif in the recognition by the hemagglutinin
      subtype-specific Z38 monoclonal antibody or by peptide-induced polyclonal
      antibodies.

PMID- 7574661
TI  - Biochemical properties of a beta-xylosidase from Clostridium cellulolyticum.
AB  - A 43-kDa beta-xylosidase from Clostridium cellulolyticum was purified to
      homogeneity. The enzyme releases xylose from p-nitrophenylxylose and xylodextrins
      with a degree of polymerization ranging between 2 and 5. The N-terminal amino
      acid sequence of the enzyme showed homologies with three other bacterial beta
      xylosidases. By proton nuclear magnetic resonance spectroscopy, the enzyme was
      found to act by inverting the beta-anomeric configuration.

PMID- 7574665
TI  - Inhibition of cellobiohydrolase I from Trichoderma reesei by palladium.
AB  - Cellulase from Trichoderma reesei is a multienzyme mixture that hydrolyzes
      cellulose to glucose. Two enzymes in this mixture, cellobiohydrolase (CBH) and
      endoglucanase (EG), possess a common structure comprising a distinct cellulose
      binding domain (CBD) and catalytic domain. Inhibition of the catalytic domain of
      cellulases without affecting their CBD function might be useful for
      structure/function studies of these enzymes. Complexes of the platinum group
      metals were tested for their ability to inhibit the major cellulase enzyme from
      T. reesei, cellobiohydrolase I (CBH I). Only palladium complexes inhibited CBH I,
      inhibition being dependent upon the molar ratio of palladium to CBH I with 1
      microM CBH I retaining only 10% of its activity in the presence of 100 microM
      ammonium hexachloropalladate(IV) and after the incorporation of 28 mol Pd/mol CBH
      I. Inhibition was irreversible and could be completely prevented by including
      histidine, cysteine, and cystine in the assay mixture. Although the primary
      mechanism of inhibition of CBH I by palladium remains to be elucidated, it could
      involve the binding of palladium to sulfur or cystine residues resulting in their
      degradation. This is based on the findings that (i) palladium-inhibited CBH I was
      less thermally stable than native CBH I; (ii) CBH I, chemically modified by the
      attachment of pentaammine ruthenium(III) to the imidazole-N of either H206 or
      H228, showed greater sensitivity to inhibition by palladium compared to native
      CBH I; and (iii) ammonium hexachloropalladate cleaved 5,5'-dithiobis(2
      nitrobenzoic acid)--Ellman's reagent. Binding of CBH I to crystalline cotton
      linters was not affected by palladium.

PMID- 7574667
TI  - ATP synthesis by purified ATP-synthase from beef heart mitochondria after
      coreconstitution with bacteriorhodopsin.
AB  - An ATP-synthase complex active in ATP synthesis was isolated from beef heart
      mitochondria by solubilization of submitochondrial particles with dodecyl-beta-D
      maltoside and purified in a one-step procedure by subsequent ion-exchange
      chromatography. The electrophoretic analysis resulted in 14 subunits for the F0
      F1 complex. ATP hydrolysis activity of the purified enzyme was 25 mumol ATP min-1
      mg-1F0F1. ATP hydrolysis could be stimulated by addition of lipid vesicles.
      Further stimulation was observed in the presence of uncoupler. The inhibitors
      dicyclohexylcarbodiimide and oligomycin reduced hydrolytic activity to 70 and
      40%, respectively. The preservation of ATP synthesis capability was demonstrated
      by reconstitution of the purified enzyme together with the light-driven proton
      pump bacteriorhodopsin. Upon illumination of ATP-synthase/bacteriorhodopsin
      proteoliposomes ATP synthesis activity was detectable for at least 7 min. At
      reduced temperature this time could be increased to 20 min. The maximum synthesis
      rate of 58 nmol ATP min-1 mg-1 F0F1 was obtained after reconstitution into
      liposomes made from crude soy bean lecithin by a detergent dialysis procedure
      using octyl-beta-D-glucopyranoside and monomeric bacteriorhodopsin. ATP synthesis
      was partially inhibited by oligomycin or dicyclohexylcarbodiimide and was
      completely abolished in the presence of uncoupler. The ability of the purified
      enzyme to synthesize ATP shows that the described isolation procedure results in
      an ATP-synthase complex which is intact in structure and function.

PMID- 7574666
TI  - Inhibition of the human immunodeficiency virus-1 protease and human
      immunodeficiency virus-1 replication by bathocuproine disulfonic acid Cu1+.
AB  - The protease encoded by the human immunodeficiency virus-1 (HIV-1) is essential
      for processing viral polyproteins which contain the enzymes and structural
      proteins required for the infectious virus. It was previously found that cupric
      chloride, in the presence of dithiothreitol or ascorbic acid, could inhibit the
      HIV-1 protease. It was suggested that a Cu1+ chelate was the moiety responsible
      for inhibition of the protease. This hypothesis has now been investigated
      directly by utilizing the stable Cu1+ chelate, bathocuproine disulfonic acid Cu1+
      (BCDS-Cu1+). BCDS-Cu1+ inhibited the HIV-1 wild type protease as well as a mutant
      HIV-1 protease lacking cysteines. BCDS-Cu1+ was a competitive inhibitor of the
      mutant HIV-1 protease with an apparent Ki of 1 microM. Replication of HIV-1 in
      human lymphocytes and the cytotoxic effect of HIV-1 in CEM cells was inhibited by
      micromolar BCDS-Cu1+. Inhibition of the protease and of HIV replication by BCDS
      Cu1+ was dependent on the presence of Cu1+ as BCDS alone was ineffective. EDTA
      blocked the inhibition of the protease by Cu1+ but was unable to block inhibition
      of the protease by BCDS-Cu1+, indicating that the Cu1+ complex was the inhibitory
      agent. The apparent IC50 for BCDS-Cu1+ on the inhibition of replication by
      primary isolates of HIV-1 was 5 microM. However, BCDS-Cu1+ did not affect
      polyprotein processing in an H9 cell line chronically infected with HIV-1,
      indicating that BCDS-Cu1+ acts by yet another mechanism to block HIV infection.
      Other possible targets for BCDS-Cu1+ include inhibition of viral adsorption
      and/or inhibition of the HIV-1 integrase.

PMID- 7574668
TI  - Effect of chronic ethanol consumption on the energy state and structural
      stability of periportal and perivenous hepatocytes.
AB  - This study was implemented to evaluate whether perivenous cells experience
      functional alterations due to a deficit in oxygen tension resulting from ethanol
      oxidation in the periportal regions of the lobule. Periportal and perivenous
      hepatocytes were prepared from ethanol-fed and control animals (Lieber-DeCarli
      diet, 31 days). These cells were either incubated at various oxygen tensions by
      varying the composition of the gases utilized to equilibrate the incubation
      buffers (0, 5, 25, and 95% oxygen) or they were unincubated. They were analyzed
      for adenine nucleotide and inorganic phosphate concentrations and from these data
      phosphorylation potentials and energy charge values were determined. Under highly
      aerobic conditions no differences were observed in the energy states of the cells
      irrespective of their source (control vs ethanol-fed; periportal vs perivenous).
      The ATP concentrations, phosphorylation potentials, and energy charge values
      indicated that the energy states of cells from both ethanol-fed and control rats
      were maintained at relatively high levels in incubations with 5 and 25% oxygen.
      However, unincubated cells and those incubated at 0% oxygen demonstrated lowered
      energy states and the decreases were most striking in hepatocytes from ethanol
      fed animals. Measurements of LDH loss and trypan blue exclusion indicate that
      cell leakage and viability loss occur when cells are incubated under anoxic and
      hypoxic conditions. At low oxygen tensions perivenous cells from ethanol-fed rats
      demonstrated much greater loss of structural stability than did the other cell
      preparations. These observations indicate that decreased energy state is one
      factor which contributes to cell damage in hepatocytes from ethanol-fed animals.
      Moreover, perivenous cells from ethanol-fed animals seem to be particularly
      vulnerable to damage under hypoxic conditions.

PMID- 7574669
TI  - Veratryl alcohol-mediated indirect oxidation of pentachlorophenol by lignin
      peroxidase.
AB  - The oxidation of pentachlorophenol (PCP) by lignin peroxidase (LiP) is
      characterized by a rapid loss of activity during which time the enzyme is quickly
      converted to compound III, an inactive form of the enzyme. We investigated the
      indirect oxidation of PCP by LiP using veratryl alcohol (VA) as a mediator. The
      oxidation of VA to veratryl aldehyde by LiP was inhibited by PCP. Inhibition was
      characterized by lag period followed by the same rate of VA oxidation. The lag
      period before VA oxidation was increased by increasing concentrations of PCP.
      During the lag period, PCP was oxidized and the extent of PCP oxidation increased
      with increasing concentrations of VA. The enzyme stayed as compound II during PCP
      oxidation in the presence of VA, suggesting that VA has a protective role in the
      LiP catalysis. The kinetics of PCP oxidation in the presence of VA were similar
      to those of VA oxidation. All these results suggest that PCP is oxidized
      indirectly via the veratryl alcohol cation radical. 2,3,5,6-Tetrachloro-p
      benzoquinone was a stoichiometric product during PCP oxidation in both the
      presence and the absence of VA. An equivalent amount of inorganic chloride was
      formed by oxidative 4-dechlorination during PCP oxidation in the presence of VA.
      The increase in the rate and extent of PCP oxidation by VA results from mediation
      of PCP oxidation and reversion of inactive compound III to native enzyme, both by
      the veratryl alcohol cation radical.

PMID- 7574670
TI  - Thermodynamic characterization of a triple-helical three-way junction containing
      a Hoogsteen branch point.
AB  - We have designed a Hoogsteen (HG) triple-helical three-way junction (ternary
      complex) constructed from three 33-mer oligonucleotides based on the same subset
      of sequences used for the Watson-Crick (WC) triple-helical three-way junction,
      characterized previously (P. L. Husler and H. H. Klump (1994) Arch. Biochem.
      Biophys., 313, 29-38). The junction differs primarily in the assembly of the
      branch point and the ends of the arms. The three oligonucleotides can each fold
      into a WC hairpin, linked by a four-member cytosine loop, each containing a homo
      pyrimidine 10-mer single-strand extension. On lowering the pH (between 6 and 4),
      the extensions mutually associate to one of the other hairpins via Hoogsteen (HG)
      hydrogen bonding. Collectively, this process results in the formation of the
      branch point and the triple-helical arms. The HG triple-helical three-way
      junction is characterized by gel electrophoresis, circular dichroism, uv melting,
      and differential scanning calorimetry. The junction undergoes thermal unfolding
      in two distinct temperature regions. In the temperature range 15 to 50 degrees C
      loss of HG base pairing results in the dissociation of the three-way junction.
      Between 55 and 95 degrees C the resulting hairpins undergo further successive
      unfolding. The overall calorimetric unfolding enthalpy and entropy changes
      associated with the loss of HG base pairing are approximately equal to the sum of
      the enthalpy and entropy changes associated with the dissociation of the HG base
      pairing in the isolated arms (170.6 kcal.mol-1; 540.1 cal.mol-1.K-1). It is
      apparent from these results that in the proximity of the branch point the
      structure is not perturb or strain. This result is contrary to the results
      obtained for the WC triple-helical three-way and for three-way junctions
      constructed from canonical double-helical DNA. Complete folding of the junction
      requires either high Na+ (600 mM) ion concentrations or 40-60 mM Mg2+.

PMID- 7574671
TI  - Interaction of anionic/nonionic surfactant mixtures with phosphatidylcholine
      liposomes.
AB  - The mechanisms governing the interaction of mixtures of sodium dodecyl sulfate
      (SDS) and nonylphenol oxyethylenated with 10 mol of ethylene oxide (NP(EO)10)
      with phosphatidylcholine liposomes were investigated. Permeability alterations
      were detected as a change in 5(6)-carboxyfluorescein (CF) released from the
      interior of vesicles and bilayer solubilization as a decrease in the static light
      scattered by liposome suspensions. Three parameters were described as the
      effective surfactant/lipid molar ratios (Re) at which the surfactant system (a)
      resulted in 50% of CF release (Re50%CF), (b) saturated the liposomes (ReSAT), and
      (c) led to a complete solubilization of these structures (ReSOL). From these
      parameters the corresponding surfactant partition coefficients (K50%CF, KSAT, and
      KSOL) were determined. Despite the fact that Re increased as the mole fraction of
      the SDS rose (XSDS), the K parameters showed maximum values at XSDS 0.6 and 0.2
      for K50%CF and KSAT, respectively, the KSOL reaching the highest value in the
      absence of SDS XSDS = 0). Thus, the higher the surfactant contribution in
      surfactant/lipid system, the lower the XSDS at which the maximum bilayer/water
      partitioning of mixed surfactant systems added took place. The free surfactant
      concentrations SW were lower than the mixed surfactant CMCs at subsolubilizing
      level, whereas it remained similar to these values during saturation and
      solubilization of bilayers in all cases.

PMID- 7574672
TI  - The isolation and characterization of four myelin basic proteins from the unbound
      fraction during CM52 chromatography.
AB  - The unbound fraction from CM52 columns was used as the source of at least four
      additional myelin basic protein (MBP) molecules. From this fraction we routinely
      obtained two major fractions called C8-A and C8-B. The C8-A and C8-B fractions
      were further purified on HPLC. Each contained two proteins in the 17- to 18-kDa
      range which we called C8-A(H) (higher M(r)), C8-A(L) (lower M(r)), C8-B(H), and
      C8-B(L). The citrulline values (calculated as citrulline plus ornithine) were
      high in three of the four proteins, which was accompanied by a compensatory
      decrease in the arginine values. The compositions clearly identified these four
      proteins with the citrullinated form of MBP. Western blot analysis showed that
      both H and L forms reacted with anti MBP antibodies. Partial sequence analysis
      after cyanogen bromide cleavage, showed that the sequences of both proteins in
      the C8-B fraction (C8-B(H) and C8-B(L)) were identical to the 18.5-kDa isoform of
      MBP. Mass spectrometry by electrospray ionization of the C8-B(H) and C8-B(L)
      provided us with accurate masses of 18,558.08 +/- 8.13 and 17,266.63 +/- 2.24,
      respectively. We concluded that the H and L proteins from the C8-B fractions were
      MBPs. Although similar detailed analyses of the C8-A(H) and C8-A(L) have not been
      done they are also considered to be MBP on the basis of the immunoreactivity with
      anti MBP antibodies. The origins of these proteins is not known at this time and
      their functional significance is obscure. The possibility that they are found in
      early forms of myelin, as components of transitional membranes between
      oligodendrocytes and myelin or are involved in remyelination, cannot be
      discounted.

PMID- 7574673
TI  - Characterization of IMT1, myo-inositol O-methyltransferase, from Mesembryanthemum
      crystallinum.
AB  - A full-length transcript, Imt1, encoding myo-inositol O-methyltransferase (EC
      2.1.1.X) from the halophyte Mesembryanthemum crystallinum was expressed in
      Escherichia coli. The enzyme, IMT1, uses S-adenosyl-L-methionine to methylate myo
      inositol to form D-ononitol. IMT1 with a monomeric mass of 41,000 was isolated by
      ammonium sulfate fractionation, gel filtration and ion exchange chromatography to
      apparent purity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      N-terminal amino acid sequence of the purified recombinant enzyme was identical
      to that encoded by the cDNA sequence. The apparent Km for S-adenosylmethionine
      was 0.18 mM with a Vmax of 1550 pkat/mg protein. The Km for myo-inositol was 1.32
      mM. The reaction became substrate-inhibited by concentrations of S
      adenosylmethionine greater than 0.5 mM. Inositol methyltransferase was
      competitively inhibited 50% with 0.01 mM S-adenosyl-homocysteine, while 1 mM
      homocysteine, homoserine, or adenosine did not inhibit. The enzyme exhibited a pH
      optimum of 7.8 and a temperature optimum of 37 degrees C. Activity of the
      isolated inositol methyltransferase was stable when stored at 4 degrees C.

PMID- 7574675
TI  - Crystal structure of human alpha-thrombin complexed with hirugen and p
      amidinophenylpyruvate at 1.6 A resolution.
AB  - Crystals of human alpha-thrombin complexed with hirugen and the alpha-keto acid
      thrombin inhibitor APPA (p-amidinophenylpyruvate) that diffract to 1.6 A
      resolution were obtained by soaking an alpha-thrombin-hirugen crystal in a
      solution of APPA. The crystal structure was determined using the difference
      Fourier method and refined to an R factor of 18.7% at 1.6 A resolution. This
      structure is the highest resolution structure of the thrombin molecule that is
      currently available. With the exception of the region near Arg77A-Asn78, the
      structures of the thrombin and hirugen molecules in the ternary complex are
      similar to those reported for the thrombin-hirugen binary complex. As previously
      determined for the APPA-trypsin complex, the carbonyl carbon atom of APPA forms a
      covalent bond with O gamma of Ser195 of thrombin to yield a "transition-state"
      analog of the tetrahedral intermediate. Comparison of the specificity pocket of
      the APPA complexes of thrombin and trypsin reveals differences in hydrogen
      bonding and shows for the first time that the S1 site of thrombin is larger than
      that of trypsin and as a result thrombin may be able to accommodate a bulkier P1
      group than trypsin.

PMID- 7574674
TI  - Active-site topology of bovine cholesterol side-chain cleavage cytochrome P450
      (P450scc) and evidence for interaction of tyrosine 94 with the side chain of
      cholesterol.
AB  - Combining site-directed mutagenesis with analysis of the active-site topology of
      bovine cholesterol side-chain cleavage cytochrome P450scc (P450scc), we have
      investigated the roles of tyrosine residues 93 and 94 on substrate binding. Four
      single mutants (Y93A, Y93S, Y94A, and Y94S) and one double mutant (Y93S/Y94S)
      were examined. The largest increase in Ks was observed for binding of cholesterol
      and 25-hydroxycholesterol to the Y94S mutant (approximately 5.5-fold), with a
      smaller increase (< 2.5-fold) for binding of 22-hydroxycholesterol. Mutation of
      Y94 thus appears to influence the interaction with cholesterol, 25
      hydroxycholesterol, and possibly 22-hydroxycholesterol. Y93 is not involved in
      binding of 22- and 25-hydroxycholesterol but may interact with cholesterol. The
      active-site topologies of P450scc and its mutants were probed by reaction with
      three arylhydrazines. The N-arylprotoporphyrin IX regioisomer patterns obtained
      with phenyl- and 2-naphthylhydrazine indicate that the active site is primarily
      open above pyrrole ring A and suggest that a region some distance above pyrrole
      ring D is also open. The single mutations Y93S, Y93A, Y94A, and Y94S do not
      detectably alter the regioisomer patterns obtained with the phenyl- and 2
      naphthyl probes, but a small, reproducible change is observed with the 2-naphthyl
      probe for the Y93S/Y94S double mutant. The conformational alteration implied by
      this change could not be detected by titration with 22- and 25-hydroxycholesterol
      but is detectable by titration with cholesterol. The results indicate that
      cholesterol binds over pyrrole ring D of the heme in bovine P450scc, strongly
      suggest that Y94 interacts with the side chain of cholesterol, and provide
      evidence that the side chains of 22- and 25-hydroxycholesterol bind to a
      different region of the active site than the side chain of cholesterol.

PMID- 7574676
TI  - Characterization and prevalence of a polymorphism in the 3' untranslated region
      of cytochrome P4501A1 in cancer-prone Atlantic tomcod.
AB  - Atlantic tomcod (Microgadus tomcod) from the cancer-prone Hudson River population
      exhibit a genetic polymorphism in the cytochrome P4501A (CYP1A) gene which is
      evidenced in Northern blot analyses by a truncated transcript and in Southern
      blot analyses by a deletion in the variant allele. To initially evaluate the
      functional significance of this polymorphism, we sought to characterize the
      molecular basis for this polymorphism and to determine its frequency in tomcod
      from other populations in which the prevalence of neoplasia is low. The common
      CYP1A allelic sequence was determined from beta-naphthoflavone-induced tomcod
      cDNA and from tomcod genomic DNA. A sequence of the variant CYP1A allele was
      obtained by direct sequence analysis of the amplicons of variant tomcod cDNA and
      genomic DNA. CYP1A exon and intron structure is highly conserved between tomcod
      and all other teleost and mammalian species compared. Similarity of the deduced
      tomcod, rainbow trout, and plaice amino acid sequences was 72%, whereas
      similarity between tomcod and mammalian sequences was approximately 50%. The
      variant tomcod CYP1A allele results from a 606-bp deletion in the 7th exon of the
      3' untranslated region (UTR) of the cDNA. Polymerase chain reaction and Northern
      blot analyses revealed an absence of this CYP1A polymorphism in tomcod from other
      rivers. Studies in humans suggest that variation in CYP1A1 cDNA may impact on
      genetic susceptibility to environmentally induced neoplasia. Furthermore, studies
      in in vitro mammalian models indicate the importance of 3' UTRs on gene
      expression by impacting on the stability of transcript. These results suggest
      that the 3' UTR CYP1A polymorphism in tomcod may have consequences for the
      genetic susceptibility of Hudson River fish to hepatic neoplasia.

PMID- 7574677
TI  - Transport of carnitine in neuroblastoma NB-2a cells.
AB  - Carnitine accumulation was measured in cultured neuroblastoma NB-2a cells. This
      process was found partially sodium dependent and its kinetics to be a sum of a
      saturable transport (Km = 123 +/- 13 microM) and diffusion (D = 63 +/- 7 pmol/mg
      protein/min/mM). On the contrary to previous reports on neural cells, the
      accumulation of carnitine was found insensitive to gamma-aminobutyric acid
      (GABA). Measurements of carnitine accumulation in the presence of different
      compounds resulted in the conclusion that carnitine transport does not occur
      through the known systems specific toward choline and/or amino acids. For
      instance, an observed inhibition of carnitine transport by serine and cysteine,
      without any effect of alanine, excluded a possible role of ASC amino acid
      transport system. An involvement of a new transporter is thus postulated,
      specific toward compounds with a polar group in the beta position with respect to
      the carboxylic group.

PMID- 7574678
TI  - Catabolism of aggrecan by explant cultures of human articular cartilage in the
      presence of retinoic acid.
AB  - The N-terminal amino acid sequence of human aggrecan was determined and it was
      shown that two sequences were present. The major sequence, AVTVE-, accounted for
      60% of the aggrecan and started at alanine residue 17 of the human aggrecan core
      protein cDNA sequence (K. Doege et al. (1991) J. Biol. Chem. 266, 894-920). The
      other N-terminal sequence, VETX-, started at valine residue 20. Characterization
      of aggrecan core protein peptides present in the matrix of adult human articular
      cartilage showed that at least 11 aggrecan core proteins were present with
      approximate M(r) between 300,000 and 43,000. All these core proteins were found
      to have the same N-terminal sequences as that observed in human aggrecan. When
      articular cartilage was placed in explant culture in medium containing 10(-6) M
      retinoic acid there was a 3.5-fold increase in the loss of aggrecan into the
      culture medium compared to tissue maintained in medium alone or medium containing
      20% (v/v) newborn calf serum. Analysis of the aggrecan core protein fragments
      that were released to the culture medium containing 10(-6) M retinoic acid showed
      the presence of 13 core protein peptides of M(r) between 300,000 and 43,000. The
      11 smaller peptides of M(r) 230,000 to 43,000 were shown to have the N-terminal
      sequence ARGS-. This sequence which starts at residue 393 of the human aggrecan
      core protein is located within the interglobular region between the G1 and G2
      domains and is the site of aggrecan catabolism by the putative protease
      aggrecanase. The presence of core proteins of varying sizes but with the same N
      terminal sequence reflects proteolytic processing from the C-terminal end of the
      core protein that was also observed in the aggrecan macromolecules extracted from
      the matrix of human articular cartilage. This proteolytic processing was also
      evident but to a lesser extent in newly synthesized 35S-labeled aggrecan
      macromolecules.

PMID- 7574680
TI  - Rapid turnover and impaired cell-surface expression of the human folate receptor
      in mouse L(tk-) fibroblasts, a cell line defective in
      glycosylphosphatidylinositol tail synthesis.
AB  - The human folate receptor (hFR) is a plasma membrane protein that is anchored to
      the membrane via a glycosylphosphatidylinositol (GPI) tail in some cell types.
      The KB hFR cDNA sequence predicts a hydrophobic, alpha-helical 31-residue
      carboxyl terminus that is thought to be the signal for cleavage and attachment of
      the GPI tail. Alternatively, this region may serve as a transmembrane domain if
      GPI attachment is not efficient. In this study, we investigated the latter
      possibility by expressing the hFR in L(tk-) cells, cells that are unable to
      synthesize GPI tails for attachment to membrane proteins. We also transfected the
      same hFR cDNA into Chinese hamster ovary (CHO) cells, cells that can anchor
      proteins by either a GPI tail or a transmembrane domain. Neither parental cell
      line expresses detectable levels of folate receptor as determined by folic acid
      binding assays, Western analysis, or Northern analysis. In L(tk-) cells, we found
      that the recombinant hFR is not expressed on the cell surface, but is rapidly
      degraded (t1/2 < or = 4 h). Most (> 95%) of the recombinant hFR remains Endo H
      sensitive, suggesting retention in the endoplasmic reticulum. In contrast,
      transfected CHO cells express functional hFR protein at the cell surface, the
      half-life of the hFR is long (t1/2 > or = 24 h), and the Endo H glycosylation
      pattern of the recombinant hFR is consistent with normal processing through the
      Golgi apparatus. Therefore, in the absence of a GPI tail, the hFR is not sorted
      to the cell surface and the incompletely processed hFR protein is unstable.

PMID- 7574679
TI  - Reduction of quinones and radicals by a plasma membrane redox system of
      Phanerochaete chrysosporium.
AB  - Quinones which are produced during the mineralization of lignin and xenobiotics
      by the white rot fungus Phanerochaete chrysosporium were reduced by a plasma
      membrane redox system of the fungus. Both intracellular enzymes and the plasma
      membrane redox system were able to reduce 1,4-benzoquinone. However, no quinone
      reductase activity was observed with the extracellular culture fluid. The
      intracellular reductase activity had a pH optimum between 6.0 and 7.0 and a Km of
      150 microM. Reduction of 1,4-benzoquinone by the plasma membrane redox system had
      a pH optimum between 7.5 and 8.5 and exhibited saturation kinetics (Km = 11
      microM, Vmax = 16 nmol/min/mg mycelia dry weight). Ferricyanide totally inhibited
      the quinone reduction until the ferricyanide was completely reduced by the
      membrane. Radicals (chlorpromazine and 2,2'-azinobis(3-ethylbenzothiazoline-6
      sulfonic acid) diammonium salt (ABTS)) that can be generated by the lignin
      peroxidases were also reduced by the plasma membrane redox system. Reduction of
      the ABTS cation radical also totally inhibited quinone reduction until the
      radical was completely reduced. Finally, quinone reduction rates were identical
      after the reduction of ferricyanide, ABTS cation radical, or quinone, suggesting
      that the plasma membrane redox system may actually protect the fungus from
      oxidative damage from free radicals generated by the lignin degrading system.

PMID- 7574681
TI  - 9,13-Di-cis-retinoic acid is the major circulating geometric isomer of retinoic
      acid in the periparturient period.
AB  - This study examines changes in the geometric isomers of retinoic acid (RA) during
      late gestation and early lactation. Blood samples were collected from dairy cows
      at 14 days prepartum and continuing until 14 days postpartum. Assays were done
      using solid-phase extraction followed by quantitation of RA isomers by reverse
      phase HPLC. The major RA in plasma of periparturient cows was 9,13-di-cis-RA.
      9,13-Di-cis-RA was present at < or = 1 ng/ml 10 days prior to parturition and was
      elevated to approximately 2 ng/ml by 1 day prepartum, then increased to > 4 ng/ml
      by 1 day postpartum. 9,13-Di-cis-RA remained at approximately 4 ng/ml for at
      least 14 days postpartum. Plasma all-trans-RA, 13-cis-RA, and 9-cis-RA were also
      elevated during the periparturient period with the most pronounced changes
      (approximately 25-30% increase) occurring between the day of parturition and 4
      days postpartum. 9,13-Di-cis-RA was 116- and 30-fold less competitive than 9-cis
      RA for binding to human retinoid X receptors (hRXR)alpha and hRXR beta,
      respectively. Because of this relatively low affinity for the RXR, it seems that
      9,13-di-cis-RA per se would contribute marginally, if at all, to the pleiotropic
      effects attributed to 9-cis-RA. This study establishes that profound changes in
      vitamin A metabolism occur in late gestation and early lactation. Because 9,13-di
      cis-RA is a metabolite of 9-cis-RA, these data imply that there are dramatic
      fluctuations in 9-cis-RA which are more profound than other physiologically
      occurring RAs, particularly all-trans-RA.

PMID- 7574682
TI  - cDNA encoding a functional feline liver/bone/kidney-type alkaline phosphatase.
AB  - Feline alkaline phosphatase (FeALP) was copurified with the putative 70-kDa
      feline leukemia virus subgroup-A (FeLV-A) receptor protein from feline T
      lymphocyte cells (FeT) by two-dimensional gel electrophoresis. The sequence of
      the N-terminal 17 amino acids and five other internal tryptic peptides revealed
      that it is homologous to the liver/bone/kidney (L/B/K)-type alkaline phosphatase
      of other mammalian species. Corresponding oligonucleotides were synthesized and
      used for amplification of a 1.2-kb segment of the FeALP gene by polymerase chain
      reaction, using phage DNA from a FeT cell cDNA library as template. The 1.2-kb
      FeALP gene fragment generated was then used as a probe to isolate a 2127-bp L/B/K
      type FeALP cDNA clone from the same library harboring a large, intact open
      reading frame. This cDNA possessed an open reading frame encoding a 524-amino
      acid protein including a putative signal peptide of 17 amino acids followed by 14
      amino-acid residues identical to the N-terminal sequence determined from the
      purified protein. Sequences closely related to five tryptic peptides from the
      purified protein were also contained within the cDNA-encoded protein. Homology
      with the human, bovine, rat and mouse L/B/K-type ALP was found to be 88-90% at
      both the nucleotide and the amino acid levels. The cDNA was transferred into a
      eukaryotic expression vector and expressed following transfection into murine and
      mink lung fibroblast cell lines. High levels of enzymatically active ALP were
      detected, along with a 70-kDa protein reactive in immunoblot assay using a
      polyclonal antibody against the original crude FeALP preparation. FeALP was
      specifically released from intact cells by treatment with phosphoinositol
      specific phospholipase-C. By Northern blot analysis, only one species of mRNA was
      detected using a 32P-labeled cDNA probe. These results indicate that the 2127-bp
      cDNA encodes a functional feline L/B/K-type ALP expressed on cell surfaces via
      phosphatidylinositol-glycan linkage. Despite electrophoretic comigration in two
      dimensions and following deglycosylation in a third dimension, FeALP failed to
      function as an FeLV receptor since its expression failed to provide for
      attachment or entry of virus into cells.

PMID- 7574683
TI  - Interactions of gelatinases with soluble and immobilized fetuin and asialofetuin.
AB  - We have analyzed the interactions of human and mouse gelatinases with fetuin and
      asialofetuin. The data showed that recombinant human gelatinase A (MMP-2) and B
      (MMP-9) were both specifically bound to asialofetuin and fetuin immobilized to
      activated agarose (affigel) with subsequent cleavage of the enzymes to lower
      molecular weight forms, which were likewise bound to asialofetuin/fetuin. The
      binding of gelatinases to immobilized forms of asialofetuin and fetuins was
      abrogated in the presence of either soluble fetuin or asialofetuin. Endogenous
      mouse macrophage gelatinases (mol wt 92 and approximately 52 kDa) were also
      specifically bound to immobilized asialofetuin upon which the two forms of the
      gelatinases were reduced to a approximately 45-kDa fragment. The binding of the
      approximately 45-kDa fragment to asialofetuin was also abrogated in the presence
      of either soluble fetuin or asialofetuin. Whereas only the activated MMP-2 bound
      to immobilized asialofetuin had significant gelatinolytic activity, both the
      zymogen and the activated forms of MMP-9 hydrolyzed soluble [3H]gelatin to the
      same extent while still bound to asialofetuin. Our data suggest that cell surface
      bound fetuin/asialofetuin could perform two functions: they could (a) act as cell
      surface receptors or anchors for MMP-2 and MMP-9 and (b) bind and activate MMP-9
      on the cell surface.

PMID- 7574684
TI  - Extracellular domain of neurotrophin receptor trkB: disulfide structure, N
      glycosylation sites, and ligand binding.
AB  - An extracellular domain of a human neurotrophin receptor trkB was expressed in
      Chinese hamster ovary cells and isolated as a glycoprotein possessing binding
      activity for brain-derived neurotrophic factor. The extracellular domain contains
      398 amino acids and has a molecular weight of 60.6 kDa according to laser
      desorption mass spectrometry, indicating that the extracellular domain of trkB
      contains 33.3% carbohydrate moieties. Six disulfide linkages were determined to
      be Cys1-Cys7, Cys5-Cys14, Cys121-Cys145, Cys123-Cys163, Cys187-Cys235, and Cys271
      Cys314, respectively. Cys300 was detected as a free sulfhydryl residue. Cysteine
      clusters 1 and 2 located in the N-terminal domain possess a similar type of
      disulfide structure and two other disulfide bonds in the C-terminal region are
      homologous to that of the Ig-like C2 domain. Among 12 potential N-linked
      glycosylation sites proposed in the soluble domain of trkB, 10 sites are actually
      glycosylated.

PMID- 7574685
TI  - Molecular engineering of microsomal P450 2a-4 to a stable, water-soluble enzyme.
AB  - Peptitergented P450 2a-4 (Pepti-P450), a water-soluble form of the mouse
      microsomal P450 2a-4, was genetically engineered and expressed in Escherichia
      coli. The NH2-terminal hydrophobic sequence (positions 2 to 19) of Pepti-P450 was
      replaced by a peptitergent PD1, amphipathic peptide consisting of 24 residues (C.
      E. Schafmeister, L. J. Miercke, and R. M. Stroud (1993) Science 262, 734-738).
      The expression level of Pepti-P450 (90,000 molecules/cell) was at least four
      times greater than that of wild-type P450 2a-4. Since Pepti-P450 was quite stable
      and was expressed as a peripheral membrane protein, it can be easily purified
      from the membrane fraction treated with Na2CO3 without using any detergents
      during the chromatographic steps. The purified Pepti-P450 retained the spectral
      and catalytic properties of the unmodified enzyme with a similar Km value for
      steroid 15 alpha-hydroxylase activity (19.7 microM in comparison to 14.2 microM
      of the wild-type). Gel permeation chromatography showed that the purified Pepti
      P450 in the detergent-free buffer was an oligomer with an approximate molecular
      mass of 450 kDa. The replacement of the hydrophobic anchor domain with an
      amphipathic helix such as peptitergent, therefore, may provide a general method
      for engineering membrane-bound P450s to soluble enzymes.

PMID- 7574686
TI  - Evidence of A1 adenosine receptor on epidydimal bovine spermatozoa.
AB  - 3H-R-phenylisopropyladenosine (PIA) was used to characterize adenosine receptors
      on bovine epidydimal spermatozoa membranes. Dypiridamole, an adenosine uptake
      inhibitor, did not effect the radioligand binding, indicating an external site
      for the interaction of adenosine with spermatozoa. Steady-state binding was
      achieved after 45 min at 25 degrees C and lasted for at least 3 h. Scatchard
      plots were linear with a Kd of 6.98 +/- 1.02 nM and Bmax of 34 +/- 8 fmol/mg
      protein. N-6-cyclopentyladenosine (CPA), with a Ki of approx. 0.196 nM, was the
      most potent inhibitor of binding and the agonist order potency series was CPA > R
      PIA = N-6-cyclohexyladenosine > N-6-phenyladenosine > 5'-N
      ethylcarboxamidoadenosine > 2-chloroadenosine > 2-(p-2-carboxyethyl)phenylamine)
      5'-N-ethylcarboxy-amidoa denosine. 1-3-Dipropyl-8-cyclopentylxanthine (DPCPX), an
      A1 receptor selective antagonist, produced the strongest inhibition with a Ki of
      0.46 +/- 0.1 nM. Antagonist order potency series DPCPX > xanthine amine congener
      > cyclopentyltheophilline = theophylline > caffeine > 1-3-dipropylxanthine > 8
      phenyltheophilline was consistent with A1 adenosine receptor (A1AR). Guanylyl-5'
      imidodiphosphate did not decrease bound 3-H-R-PIA nor accelerate its
      dissociation, a behavior consistent with inhibitory receptors only. The
      incubation of isolated membranes with N-ethylmaleimid followed by a reduction of
      57% of the ligand binding further supports the existence of A1AR on bovine
      epidydimal spermatozoa.

PMID- 7574687
TI  - Marked effects of alcohols and imidazoles on the cumyl hydroperoxide reaction
      with the wild-type cytochrome P450 1A2.
AB  - Cytochrome P450 catalyzes monooxidation reactions of many organic compounds in
      the presence of hydroperoxides even in the absence of electron-transfer proteins
      and molecular oxygen. To understand the mechanism of the hydroperoxide-induced
      cytochrome P450 reactions, we investigated effects of ligands such as alcohols
      and imidazoles and 7-ethoxycoumarin, a substrate of cytochrome P450 1A2 (P450
      1A2), on the cumyl hydroperoxide (CHP) O-O cleavage reaction with wild-type P450
      1A2. Formation rates of cumyl alcohol from CHP with P450 1A2 were remarkably
      enhanced up to 25-fold by adding alcohols, whereas those of acetophenone were not
      changed by the same procedure. 2-Methylimidazole did not essentially influence
      the CHP reaction with P450 1A2, while 4-methylimidazole hampered the cumyl
      alcohol formation. 7-Ethoxycoumarin also impeded the cumyl alcohol formation with
      P450 1A2. These CHP reactions with P450 1A2 under various conditions are
      consistent with P450 1A2 spectral changes with CHP obtained under the same
      conditions. The present study suggests that the several ligands such as alcohols
      and imidazoles have marked effects on the heterolytic O-O cleavage reaction of
      CHP with P450 1A2. Mechanisms of the peroxide O-O scission with P450 1A2
      associated with the distal site structure and substrate binding are discussed.

PMID- 7574688
TI  - Sc3+, Ga3+, In3+, Y3+, and Be2+ promote changes in membrane physical properties
      and facilitate Fe2(+)-initiated lipid peroxidation.
AB  - The capacity of metals chemically and physically related to Al (Sc, Ga, In, Y,
      and Be) to promote liposome aggregation, fusion, and permeabilization and to
      stimulate Fe2(+)-initiated lipid peroxidation was investigated in negatively
      charged liposomes. The effects of Sc, Ga, In, Be, and Y were compared with those
      of trivalent (Al, La) and divalent cations. At 50 microM concentration, Al, Sc,
      Ga, In, Y, and La released 5(6)-carboxyfluorescein from liposomes and the
      magnitude of the effect was Al, In > Ga, Sc > La, Y. At concentrations between 10
      and 200 microM, Sc, Ga, In, Y, and Be caused liposome aggregation and fusion. Al,
      Sc, Ga, In, and Be had their maximal effect on liposome fusion and aggregation at
      100 microM; Y and La had their maximal effect at 20 microM. Metal-induced fusion
      was dependent on the negative charge density of the liposomes. Sc, Ga, In, Be,
      and Y stimulated Fe2(+)-initiated lipid peroxidation in a time- and dose
      dependent manner. The fusogenic capacity of these nonredox metals was positively
      correlated with their capacity to induce Fe2(+)-supported lipid peroxidation.
      Results suggest that metals without redox capacity can promote lipid
      peroxidation, in the presence of an initiator of the oxidative chain, by
      affecting membrane physical properties.

PMID- 7574689
TI  - A superoxide dismutase mimic protects sodA sodB Escherichia coli against aerobic
      heating and stationary-phase death.
AB  - Superoxide appears to be a major cause of stationary-phase death and heat kill.
      In support of this conclusion are the following observations: (a) Stationary
      phase death was apparent in the sodA sodB, but not in the superoxide dismutase
      (SOD)-competent parental strain; (b) Stationary phase death in the sodA sodB
      strain was dioxygen-dependent; (c) A manganic porphyrin, which catalyzes the
      dismutation of superoxide, protected the sodA sodB strain against stationary
      phase death; (d) Heating the sodA sodB strain to 42 degrees C caused a loss of
      viability not seen with the SOD-competent parental strain and preventable by the
      manganic porphyrin. Exposure to aerobic conditions induced antibiotic resistance
      in the sodA sodB, but not in the parental strain and the manganic porphyrin
      prevented that induction. This again indicates its ability to substitute for SOD
      in Escherichia coli.

PMID- 7574690
TI  - Participation of the propeptide on procathepsin D activation of human peripheral
      lymphocytes and neutrophils.
AB  - Flow cytometry was used to test the role of the propeptide of procathepsin D in
      the activation of human peripheral lymphocytes and neutrophils. A selective
      inhibition of the activation was achieved by antibodies targeted against the
      propeptide. Synthetic peptide corresponding to the cathepsin D propeptide had a
      very similar effect as procathepsin D itself. The interaction of procathepsin D
      with the cells was blocked by the propeptide as monitored in experiments with
      fluorescently labeled procathepsin D. Our data indicate that procathepsin D
      activation of human neutrophils and leukocytes described earlier is mediated
      through the propeptide of the procathepsin D.

PMID- 7574691
TI  - Superoxide dismutase abolishes the platelet-derived growth factor-induced release
      of prostaglandin E2 by blocking induction of nitric oxide synthase: role of
      superoxide.
AB  - The ability of platelet-derived growth factor (PDGF) to induce prostaglandin E2
      (PGE2) release in fibroblasts is abolished when copper-zinc superoxide dismutase
      activity is increased by transfection of an expression vector. The effect is
      specific to copper-zinc superoxide dismutase as glutathione peroxidase
      overexpressing NIH3T3 cells, again produced by transfection of an expression
      vector, retain the ability to release PGE2 in response to growth factor
      stimulation. The defect in PDGF-induced PGE2 release occurs prior to action of
      prostaglandin H synthase/cyclooxygenase as release of arachadonic acid (in
      response to PDGF) does not occur in the superoxide dismutase-overexpressing
      clones. The defect in PDGF-induced release of PGE2 in superoxide dismutase
      overexpressing clones differs from the defect found in pEJ-ras-transformed
      clones. The parent cells, the glutathione peroxidase-expressing cells, and the
      superoxide dismutase-overexpressing cells all release PGE2 in response to
      exogenous nitric oxide, whereas the pEJ-ras-transformed cells do not. The
      glutathione peroxidase-expressing cells also retained the ability to release
      nitrite in response to PDGF, whereas the superoxide dismutase-expressing clones
      do not. PDGF stimulates nitric oxide synthase activity in NIH3T3 cells, but not
      in the superoxide dismutase-expressing clones. These results indicate that
      superoxide dismutase overexpression blocks the PDGF-induced release of PGE2 by
      blocking induction of nitric oxide synthase. This indicates that the increase of
      nitric oxide synthase induced by PDGF is mediated in part by production of
      superoxide. These findings link cellular oxygen radical homeostasis to three
      different classes of messenger molecules (growth factors, nitric oxide, and
      prostaglandins).

PMID- 7574692
TI  - Kinetics of the reaction of baker's yeast glucose-6-phosphate dehydrogenase with
      5,5'-dithiobis(2-nitrobenzoic acid).
AB  - The kinetics of the reaction of baker's yeast glucose-6-phosphate dehydrogenase
      with excess 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) were studied at pH 8.5 and
      30 degrees C and at constant ionic strength of 0.01 and in the absence and in the
      presence of NADP+ or glucose 6-phosphate. The reaction follows pseudo-first-order
      kinetics irrespective of whether these substrates are absent or present. The
      observed pseudo-first-order rate constant is reduced in the presence of NADP+ or
      glucose 6-phosphate but on a molar basis, glucose 6-phosphate is more effective
      than NADP+ in protecting the sulfhydryl groups of the enzyme against the reaction
      with DTNB. In the presence of NADP+, the observed pseudo-first-order rate
      constant decreases to a constant, but finite, value at a saturating coenzyme
      concentration. The effect of NADP+ on the rate constant is consistent with the
      presence of noninteracting coenzyme binding sites in baker's yeast glucose-6
      phosphate dehydrogenase.

PMID- 7574693
TI  - Stringency of substrate specificity of Escherichia coli malate dehydrogenase.
AB  - Malate dehydrogenase and lactate dehydrogenase are members of the structurally
      and functionally homologous family of 2-ketoacid dehydrogenases. Both enzymes
      display high specificity for their respective keto substrates, oxaloacetate and
      pyruvate. Closer analysis of their specificity, however, reveals that the
      specificity of malate dehydrogenase is much stricter and less malleable than that
      of lactate dehydrogenase. Site-specific mutagenesis of the two enzymes in an
      attempt to reverse their specificity has met with contrary results. Conversion of
      a specific active-site glutamine to arginine in lactate dehydrogenase from
      Bacillus stearothermophilus generated an enzyme that displayed activity toward
      oxaloacetate equal to that of the native enzyme toward pyruvate (H. M. Wilks et
      al. (1988) Science 242, 1541-1544). We have constructed a series of mutants in
      the mobile, active site loop of the Escherichia coli malate dehydrogenase that
      incorporate the complementary change, conversion of arginine 81 to glutamine, to
      evaluate the role of charge distribution and conformational flexibility within
      this loop in defining the substrate specificity of these enzymes. Mutants
      incorporating the change R81Q all had reversed specificity, displaying much
      higher activity toward pyruvate than to the natural substrate, oxaloacetate. In
      contrast to the mutated lactate dehydrogenase, these reversed-specificity mutants
      were much less active than the native enzyme. Secondary mutations within the loop
      of the E. coli enzyme (A80N, A80P, A80P/M85E/D86T) had either no or only
      moderately beneficial effects on the activity of the mutant enzyme toward
      pyruvate. The mutation A80P, which can be expected to reduce the overall
      flexibility of the loop, modestly improved activity toward pyruvate. The possible
      physiological relevance of the stringent specificity of malate dehydrogenase was
      investigated. In normal strains of E. coli, fermentative metabolism was not
      affected by expression of the mutant malate dehydrogenase. However, when
      expressed in a strain of E. coli unable to ferment glucose, the mutant enzyme
      restored growth and produced lactic acid as the sole fermentation product.

PMID- 7574694
TI  - Stopped-flow kinetic study of the reaction of ascorbic acid with peroxynitrite.
AB  - A new mechanism is presented for the oxidation of ascorbate by peroxynitrite. Our
      mechanism involves the reaction of ascorbate both with ground-state peroxynitrous
      acid (HOONO) and with a reactive intermediate (HOONO*); the reactive intermediate
      is postulated to be formed in the decay of HOONO to form nitrate. At
      physiological pH, the ascorbate monoanion (AH-) is the predominant ascorbate
      species. The plot of the observed rate constant for peroxynitrite decay (kobs) vs
      AH- for the reaction of peroxynitrite with AH- shows two regions, one linear and
      one curved. In the linear region, which involves high AH- concentrations, the
      reaction is dominated by the bimolecular reaction between HOONO and AH-. At lower
      AH- concentrations, this bimolecular reaction slows and reactions with both HOONO
      and HOONO* produce the observed curvature. Analysis of the data leads to the
      estimation of the ratio of rate constants for the reaction of AH- with HOONO*
      (k2*) and the decay of HOONO to nitrate (kN), giving the value of k2*/kN = 3158
      +/- 505 M-1; and of the rate constant (k2) for the reaction between AH- and
      HOONO, k2 = 236 +/- 14 M-1 s-1. Ascorbate displays higher selectivity for HOONO*
      than does methionine or 2-keto-4-thiomethylbutanoic acid, two substrates whose
      reactivity toward HOONO and HOONO* has previously been reported. The biological
      relevance of the reaction of ascorbate with peroxynitrite is discussed in terms
      of the rate constants and the concentrations of AH- typically found in biological
      systems; ascorbate may react with HOONO*, although the reaction with ground-state
      HOONO probably is too slow to occur in vivo.

PMID- 7574695
TI  - Synthesis and characterization of thiobutyltriphenylphosphonium bromide, a novel
      thiol reagent targeted to the mitochondrial matrix.
AB  - Mitochondria are continually exposed to oxidative stress due to superoxide
      formation by the respiratory chain which increases in pathological situations
      such as ischemia reperfusion and neurodegeneration. During oxidative stress there
      are a number of changes in mitochondrial low-molecular-weight and protein thiols.
      In particular, the mitochondrial glutathione pool becomes oxidized and forms
      mixed disulfides with protein thiols. To investigate changes in the redox state
      and conjugation of mitochondrial glutathione, and other mitochondrial thiols, we
      designed and characterized a thiol probe specifically targeted to the
      mitochondrial matrix. This molecule, thiobutyltriphenylphosphonium bromide,
      contains a thiol group linked to a lipophilic triphenylphosphonium cation which
      causes it to accumulate in the negatively charged mitochondrial matrix. Using
      [14C]thiobutyltriphenylphosphonium bromide we confirmed that it was selectively
      accumulated by isolated mitochondria. In the mitochondrial matrix the thiol group
      equilibrated with endogenous thiols and during oxidative stress became disulfide
      bonded to protein and nonprotein thiols. Therefore, this novel thiol probe can be
      used to label protein thiol groups and to investigate changes in conjugation and
      redox state of mitochondrial thiols during oxidative stress.

PMID- 7574696
TI  - Purification and characterization of malate dehydrogenase from Cryptococcus
      neoformans.
AB  - The NAD-dependent malate dehydrogenase (EC 1.1.1.37) was purified from
      Cryptococcus neoformans, a basidiomycetious yeast that is an opportunistic
      pathogen of AIDS patients. The purified enzyme was a dimer of 35 kDa subunits
      that exhibited uncompetitive substrate inhibition by oxalacetate, typical for
      mitochondrial malate dehydrogenases from other sources. Product inhibition
      studies indicated an ordered sequential kinetic mechanism, with pyridine
      dinucleotide being the substrate that binds to the free enzyme form. Unique
      aspects of this malate dehydrogenase were inhibition by zinc ion, competitive
      versus malate with Ki of 30 microM, and inhibition by heparin. Heparin inhibition
      was competitive versus either NAD or malate, with Ki of 0.35 microM. Heparin
      molecules of nominal molecular weight of 30,000 or 3000 were equally effective
      inhibitors. A model is presented to explain the high affinity of the enzyme for
      heparin.

PMID- 7574697
TI  - Molecular cloning, expression and characterization of an endogenous human
      cytochrome P450 arachidonic acid epoxygenase isoform.
AB  - A cDNA containing an open reading frame coding for a human cytochrome P450
      arachidonic acid epoxygenase was isolated from a male human kidney cDNA library.
      Sequence analysis showed that, with few exceptions, this cDNA was nearly
      identical to the published sequence for human liver Cyp 2C8 (S. T. Okino et al.,
      1987, J. Biol. Chem. 262, 16072-16079) and encoded a polypeptide of 490 amino
      acids. Nucleic acid hybridization indicated that: (a) Cyp 2C8 and 2C10 were
      expressed at comparable levels in the human liver and (b) compared to Cyp 2C10,
      the steady state concentrations of Cyp 2C8 transcripts in the human kidney were
      substantially lower. The kidney 2C8 cDNA was cloned into a pBlue BacIII vector,
      expressed using a baculovirus/Sf9 insect cell system, and the recombinant Cyp 2C8
      protein was purified by a combination of hydrophobic and hydroxylapatite
      chromatography. Purified recombinant Cyp 2C8 and 2C10 were reconstituted in the
      presence of NADPH and NADPH-cytochrome P450 reductase and shown to metabolize
      arachidonic via olefin epoxidation with both proteins generating, almost
      exclusively, epoxygenase-derived products (94 and 90% of total products,
      respectively). Catalytic turnover (1.05 and 0.75 nmol of product/nmol of
      hemoprotein/min at 30 degrees C for Cyp 2C8 and 2C10, respectively) was inhibited
      by the addition of purified cytochrome b5. Metabolism by recombinant 2C8 was both
      regio- and enantioselective for 11(R), 12(S)- and 14(R), 15(S)
      epoxyeicosatrienoic acids (82% optical purity, each). Compared to Cyp 2C8,
      arachidonic acid epoxidation by Cyp 2C10 was less regio- and stereo-selective and
      generated mixtures of 8(S), 9(R)-, 11(S), 12(R)-, and 14(R), 15(S)
      epoxyeicosatrienoic acids (with optical purities of 66, 69, 63%, respectively).
      Importantly, recombinant Cyp 2C8 and 2C10 epoxidized the arachidonic acid 11, 12
      olefin with opposite enantiofacial selectivities. Only for Cyp 2C8 did the
      chirality of the products match that of the enantiomers present, in vivo, in
      human kidney cortex (A. Karara et al., 1990, FEBS Lett. 268, 227-230). Hence, we
      propose that Cyp 2C8 is one of the human cytochrome P450 isoforms responsible for
      the metabolism of endogenous arachidonic acid pools.

PMID- 7574698
TI  - Matrix damage and chondrocyte viability following a single impact load on
      articular cartilage.
AB  - An impact load was applied to full-depth circular samples of articular cartilage
      in vitro and the effects of impact energy and velocity on matrix integrity and
      chondrocyte viability were studied. Following a severe impact, calculated to
      correspond to the energy density over the cartilage surface that might be
      expected in a man jumping off a 1-m-high wall, the tissue was grossly disrupted.
      It became elliptical, fissured, and flattened. Cartilage samples remaining
      attached to the underlying bone showed less damage at similar drop masses and
      heights. Chondrocyte viability was found to decrease linearly with increasing
      impact energy. Cartilage biopsies maintained in culture for up to 15 days
      following impact gained mass over the first 3 days which they did not
      subsequently lose. The gain in mass increased with the severity of impact and was
      due to an increased hydration of the tissue. Scanning electron microscopy and
      light microscopy showed fissures penetrating the tissue but which were never
      found to pass through the full depth. They were commonly oriented at about 45
      degrees to the plane of the surface and gave the appearance of being deflected
      parallel to the surface on reaching the transition zone. This produced a
      "delaminating" effect where the surface zone was separating from the deep zone.

PMID- 7574699
TI  - Osmotic properties of myosin subfragment 1: implications of the mechanism of
      muscle contraction.
AB  - The osmotic behavior of myosin subfragment 1 was studied at 22 degrees C and pH
      7.45 in 0.1 m KCl, 2 mm MgCl2, and 10 mm triethanolamine or in 25 mm phosphate, 2
      mm MgCl2, and 2 mm MgADP. It was found that, in 0.1 m KCl, myosin subfragment 1
      behaved as a spheroidal particle, with an average diameter of 8.09 nm, composed
      of two myosin subfragment 1 molecules. The lower limit of the thermodynamic
      dimerization constant was estimated to be 3.5 x 10(4) M-1. Above 5 mm as monomer,
      myosin subfragment 1 departed from the behavior expected of a dimeric spheroidal
      model because of the onset of a "hydration force." This force measured at the
      contact distance between particles equals 2.18 x 10(7) dynes/cm2 and falls off
      exponentially with a decay distance of 0.27 nm. In 25 mm orthophosphate, myosin
      subfragment 1, with an increase in the protein osmotic pressure, shifted from the
      behavior of a sphere to that of a cylinder. Between 1 x 10(5) and 4 x 10(5)
      dynes/cm2, the behavior of myosin subfragment 1 was different in the presence and
      in the absence of MgADP. In particular, at 1.8 x 10(5) dynes/cm2, the protein
      osmotic pressure in frog muscle, myosin subfragment 1 behaved as a sphere of 3.21
      nm radius in the presence of MgADP and as a cylinder with a length to diameter
      ratio of 2.07 in the absence of MgADP. Under the solution conditions used in this
      work, S1 never behaved as a fully extended particle.

PMID- 7574700
TI  - Recognition of type 1 chain oligosaccharides and lacto-series glycolipids by an
      antibody to human secretory component.
AB  - Binding of the mouse IgM antibody 6C4 is lost after treatment of human free
      secretory component with peptide N-glycosidase F (Bakos et al. (1991) J. Immunol.
      146, 162-168) or periodate, suggesting that asparagine-linked oligosaccharides
      contain the epitope recognized by this antibody. Inhibition of antibody binding
      to free secretory component by milk oligosaccharides established that lacto-N
      tetraose is the minimum structure recognized by the antibody, but larger
      oligosaccharides with terminal Gal beta 1-3GlcNAc sequences bind with much higher
      affinity. Antibody binding is enhanced by substitution with the Lewis Fuc alpha 1
      4 and is inhibited by Fuc alpha 1-2Gal substitution. Free secretory component,
      however, does not bind other antibodies that recognize Le(a) or Leb
      oligosaccharides, and binding is lost after digestion with a beta-galactosidase
      that cleaves Gal beta 1-3 linkages but not after digestion with alpha-L
      fucosidase. Therefore, the major epitope recognized by 6C4 on free secretory
      component is probably not an asparagine-linked Le(a) oligosaccharide. The
      antibody also binds to human milk lactoferrin, some human mucins, and lacto
      series glycolipids including III4 alpha Fuc-lactotetraosyl ceramide and
      lactotetraosyl ceramide. Based on affinity chromatography of oligosaccharides
      released from free secretory component, the epitope recognized by antibody 6C4 is
      present on approximately 3.5% of the asparagine-linked oligosaccharides.

PMID- 7574701
TI  - Incorporation of exogenous fatty acids into molecular species of rat hepatocyte
      phosphatidylcholine.
AB  - Freshly isolated rat hepatocytes were incubated for 20 and 60 min with [U
      14C]glycerol and unlabeled palmitic (16:0), oleic (18:1), or arachidonic (20:4)
      acid, added as albumin complex in 10% ethanol. Each fatty acid increased glycerol
      incorporation into total lipids by a factor of 8-10 over control, whereas ethanol
      alone (final concentration 100 mM) yielded a threefold increase of glycerol
      uptake. Glycerol incorporation stopped after 20 min and cellular acyl turnover
      continued in the absence of useable labeled substrate. In each case,
      radioactivity recovered in hepatocyte lipids was present primarily in
      triacylglycerol (37-64%), phosphatidylcholine (22-37%), and
      phosphatidylethanolamine (10-22%). Separation by high-performance liquid
      chromatography of the diacylglycerol dinitrobenzoates derived from
      phosphatidylcholine showed that the molecular species had drastically different
      labeling patterns in the presence of the exogenous fatty acids, whereas the
      pattern obtained in the presence of ethanol alone was virtually the same as that
      for the control incubations. The labeling patterns indicated that exogenous fatty
      acids, including arachidonic acid, were incorporated into phosphatidylcholine
      primarily by the de novo pathway yielding highly labeled species with the
      exogenous fatty acid esterified at both the sn-1 and sn-2 positions of glycerol.
      After 20 min incubation with arachidonic acid, the 20:4-20:4 phosphatidylcholine
      contained about one-half of the [U-14C]glycerol label recovered in this lipid
      class. The data also showed that newly synthesized molecular species were
      extensively remodeled within 1 h.

PMID- 7574702
TI  - Isolation, characterization, and functional role of the high-potential iron
      sulfur protein (HiPIP) from Rhodoferax fermentans.
AB  - A new high-potential iron-sulfur protein (HiPIP) has been isolated and purified
      to homogeneity from the soluble fraction obtained from light-grown cells of the
      facultative photoheterotrophic bacterium Rhodoferax fermentans. The new protein
      was identified as a HiPIP by virtue of its molecular properties such as the
      molecular mass (M(r) = 8.7 kDa), the Fe/protein ratio (3.8 +/- 0.2), the
      reduction potential (Em,7 = +351 mV), the electronic spectrum of the reduced and
      the oxidized protein, and the EPR spectrum of the oxidized protein. These
      molecular properties lie in the range observed for HiPIPs from other sources and,
      in particular, the iron content is consistent with the presence of one [Fe4S4]
      cubane cluster per molecule. The isoelectric pH values of the two redox forms are
      consistent with a basic protein. Kinetic studies of HiPIP oxidation, performed by
      monitoring the absorbance changes induced upon light excitation of the
      photosynthetic reaction center, give direct evidence of the role of the HiPIP in
      the photosynthetic electron transfer chain of Rf. fermentans.

PMID- 7574704
TI  - Finding of a homarine-synthesizing enzyme in turban shell and some properties of
      the enzyme.
AB  - A homarine-synthesizing enzyme was found for the first time in cell-free extract
      from turban shell (Batillus cornutus) and the enzyme was purified 36.2-fold and
      characterized. Properties of the enzyme were as follows: substrates were
      picolinic acid (pyridine-2-carboxylic acid) and S-adenosyl-L-methionine; optimum
      temperature for the enzymic reaction was 25 degrees C; optimum pH for the enzymic
      reaction was 6.3; and the Km values for picolinic acid and S-adenosyl-L
      methionine were calculated at 317 and 14.5 microM, respectively. Among pyridine
      carboxylic acids, only picolinic acid was methylated with S-adenosyl-L-methionine
      by this enzyme. The molecular weight of the enzyme was estimated to be 70,800.
      The enzyme activity was inhibited by heavy metal ions, S-adenosyl-L-homocysteine,
      adenosine, homocysteine, and sinefungin. Homarine, which is an osmotic pressure
      regulator, morphogen, etc.; is enzymatically synthesized by the methylation of
      picolinic acid with S-adenosyl-L-methionine and the enzyme activity may be
      controlled by S-adenosyl-L-homocysteine (reaction product) and its related
      compounds.

PMID- 7574703
TI  - Decreased m3-muscarinic and alpha 1-adrenergic receptor stimulation of PIP2
      hydrolysis in parotid gland membranes from aged rats: defect in activation of G
      alpha q/11.
AB  - m3-Muscarinic cholinergic receptor (m3-AChR) and alpha 1-adrenergic receptor
      (alpha 1-AR) stimulation of phosphatidylinositol 4,5-bisphosphate (PIP2)
      hydrolysis (by a PIP2-specific phospholipase C, PLC) in rat parotid gland
      membranes is mediated via activation of alpha subunits of the Gq/11 family of G
      proteins. This study examines m3-AChR and alpha 1-AR stimulation of PIP2
      hydrolysis in membranes isolated from parotid glands of old (24 months) and young
      (3 months) rats (old and young rat membranes). Old rat membranes exhibited
      reduced stimulation of PIP2 hydrolysis in response to the addition of guanosine
      5'-O-(3-thiotrisphosphate) (GTP gamma S) alone or GTP gamma S plus either
      carbachol (m3-AChR agonist) or epinephrine (alpha 1-AR agonist). This reduction
      in receptor-stimulated PIP2 hydrolysis was not due to a decrease in PLC activity
      per se since cholate-solubilized PLC activity was similar in old and young rat
      membranes. Additionally, these membranes exhibited comparable, immunologically
      detectable, levels of PLC beta 3, G alpha q/11, and G beta. In the presence of 10
      microM AlCl3 and 10 mM NaF, stimulation of PIP2 hydrolysis in both old and young
      rat membranes was similar. Preincubation of membranes from old rats with GTP
      gamma S induced a time-dependent increase in the rate of PIP2 hydrolysis and,
      with 20 min preincubation, the rates of hydrolysis in old and young rat membranes
      were not statistically different. In aggregate, these data indicate that there is
      a defect in the activation of G alpha q/11 in parotid gland membranes from old
      rats.

PMID- 7574705
TI  - Identification of several isoforms of T-kininogen expressed in the liver of aging
      rats.
AB  - We have previously shown that senescent Sprague-Dawley rats have significantly
      increased levels of kininogen (KG) mRNA and protein, when compared with younger
      counterparts. In the rat, five different isoforms of kininogen have been
      identified: high-molecular-weight K-kininogen, low-molecular-weight K-kininogen,
      and T1 alpha, T1 beta, and T2 kininogens. Several of these isoforms have been
      shown to differ in their biological properties. It was therefore considered
      relevant to establish which of these isoforms are expressed in the liver of old
      rats. To this end, we have isolated and sequenced nine independent cDNA clones
      from a library constructed using liver mRNA from healthy senescent rats.
      Predicted protein sequences indicate the presence of T-kininogens only. The
      relative lack of induction of K-kininogens during aging was further confirmed by
      RNA hybridization experiments. The nucleotide sequences reveal a
      microheterogeneity of silent polymorphisms, suggesting the presence and
      expression of several different alleles of the genes. From our data we conclude
      that (i) Several isoforms of T-KG are expressed in the liver of senescent Sprague
      Dawley rats and (ii) T1 kininogens appear to be the most highly represented T-KG
      mRNA species in old rat livers.

PMID- 7574706
TI  - Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain
      breaking antioxidants.
AB  - The purpose of this investigation was to establish the relative antioxidant
      activities in vitro of the flavanolic polyphenols, the catechins, and catechin
      gallate esters. The relative antioxidant potentials were measured against
      radicals generated in the aqueous phase and against propagating lipid peroxyl
      radicals. The results show that in the aqueous phase their order of effectiveness
      as radical scavengers is epicatechin gallate (ECG) > epigallocatechin gallate
      (EGCG) > epigallocatechin (EGC) > gallic acid (GA) > epicatechin congruent to
      catechin; against propagating lipid peroxyl radical species, epicatechin and
      catechin are as effective as ECG and EGCG, the least efficacious being EGC and
      GA. This is consistent with their relative abilities to protect against
      consumption of LDL alpha-tocopherol. The results are discussed in the context of
      the most relevant antioxidant constituents of green tea extracts.

PMID- 7574707
TI  - Induction and purification of cytochrome P450 1A1 from 3-methylcholanthrene
      treated tilapia, Oreochromis niloticus x Oreochromis aureus.
AB  - Pretreatments of freshwater fish tilapia, Oreochromis niloticus x O. aureus, with
      3-methylcholanthrene (3-MC) and polychlorinated biphenyls (PCBs) increased liver
      microsomal cytochromes P450 (P450) and b5 contents, benzo[a]pyrene hydroxylation,
      and 7-ethoxyresorufin and 7-ethoxycoumarin O-dealkylations. The pretreatments
      also increased gill microsomal benzo[a]pyrene and 7-ethoxyresorufin oxidations.
      Immunoblot analysis of liver and gill microsomes revealed that 3-MC and PCBs
      induced a protein recognized by the mouse monoclonal antibody (MAb) 1-12-3
      against scup P450 1A1. Northern analysis of liver and gill RNA showed that 3-MC
      and PCBs increased the intensity of 2.9-kb- and 1.5-kb-sized mRNA bands
      hybridizable to a trout P450 1A1 cDNA probe. Pretreatment with phenobarbital was
      without effects on the monooxygenase activity or protein or mRNA levels in liver
      and gill. A 3-MC-inducible P450 hemoprotein (M(r) = 59,000) and a NADPH
      cytochrome P450 reductase flavoprotein (M(r) = 74,000) were purified from liver
      microsomes. The tilapia P450 hemoprotein showed an absorption maximum at 447 nm
      in CO-difference spectrum and a strong immunoreactivity with MAb 1-12-3. A
      reconstituted tilapia monooxygenase system consisting of P450 and NADPH
      cytochrome P450 reductase was effective in the catalysis of 7-ethoxyresorufin,
      benzo[a]pyrene, and 7-ethoxycoumarin oxidations, but not in N
      nitrosodimethylamine demethylation. These results show that 3-MC and PCBs can
      induce P450 1A1 in tilapia liver and gill and the tilapia P450 is highly similar
      to other teleost P450 1A1 with respect to spectral, immunochemical, and catalytic
      properties.

PMID- 7574708
TI  - Anomeric specificity of rat hepatic 6-phosphofructo-2-kinase: an NMR study.
AB  - The anomeric specificity of 6-phosphofructo-2-kinase for D-fructose-6-phosphate
      was determined by nuclear magnetic spectroscopy. A mutant 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase (His258-Ala) was used to minimize degradation
      of fructose-2,6-bisphosphate by the bisphosphatase activity. The 1H NMR spectrum
      of the fructose-2,6-bisphosphate formed from the reaction was identical in the
      spectral region (3.5 to 4.0 ppm) to that reported for D-fructose-2,6-bisphosphate
      by Voll et al. (7). The integration of this region accounted for the 7
      nonexchangeable protons of the furanose form of fructose. The measured coupling
      constants and the chemical shifts were identical to those of commercially
      prepared D-fructose-2,6-bisphosphate. The long range (through 4-bond: P-2, O-2, C
      2, C-3, and H-3) coupling between P-2 and H-3, 4JH-3, P-2, was found to be 1.06
      Hz and provides strong evidence for the beta-anomer. Additionally, failure to
      find a similar coupling to the H-la peak ruled out the possibility of existence
      of the alpha-anomer. These results indicate that only beta-D-fructose-2,6
      bisphosphate was synthesized via the 6-phosphofructo-2-kinase reaction. It was
      concluded that 6-phosphofructo-2-kinase has an absolute stereo specificity for
      the beta-anomer of D-fructose-6-phosphate.

PMID- 7574709
TI  - Terminal marking of triosephosphate isomerase: consequences of deamidation.
AB  - Mammalian triosephosphate isomerase spontaneously deamidates at Asn71 and Asn15
      located at the subunit interface of the isologous dimer. These deamidations have
      been proposed to constitute the terminal marking event in the degradation of the
      enzyme. A series of physical and chemical studies detailed here reveals that the
      overall structure of the enzyme is substantially altered by these deamidations.
      The far-uv CD spectra show a 30% lower secondary structure with a blue shifted
      ellipticity minimum and increased fluorescence (10-22%) with a red-shifted
      emission maximum (8.7-15.6 nm) indicates exposure of tryptophans to a more polar
      environment. Increased binding of the fluorescent hydrophobic probe 1,1'-bis(4
      anilino)-naphthalene-5,5'-disulfonic acid to the deamidated enzyme corroborates
      these spectral observations and also suggests that the hydrophobic residues at
      the subunit interface are exposed as a result of the deamidation. Decreased
      subunit cross-linking (80 vs 20%) of the deamidated enzyme by the bifunctional
      reagent ethylene glycolbis (succinimidylsuccinate) also indicates a loosening of
      the two subunits at the interface. These structural changes are accompanied by a
      decreased thermal stability (3.1 degrees C lower Tm) and an increased
      susceptibility to dissociation in urea. The terminal marking also results in the
      generation of new proteolytic sites and increases the susceptibility to
      proteolysis. Hybrid dimers from rabbit and yeast (lacking Asn71) showed that
      deamidation of the rabbit Asn71-yeast Asn15 pair does not accelerate deamidation
      of the remaining rabbit Asn15 site, indicating that deamidation of Asn71 is a
      prerequisite for deamidation of Asn15. These studies are consistent with the
      proposal that the specific deamidations at the subunit interface cause
      significant structural changes which lead to degradation of the protein.

PMID- 7574710
TI  - Purification and characterization of recombinant cytochrome P450TYR expressed at
      high levels in Escherichia coli.
AB  - The multifunctional tyrosine N-hydroxylase, cytochrome P450TYR (CYP79), from
      Sorghum bicolor catalyzing the conversion of tyrosine to p-hydroxyphenyl
      acetaldoxime in the biosynthesis of the cyanogenic glucoside dhurrin, has been
      expressed in Escherichia coli using the isopropyl-beta-D-thiogalactopyranoside
      inducible vector pSP19g10L, containing the cDNA encoding CYP79. The expression
      construct was optimized by reducing the length of the N-terminal hydrophobic core
      of the signal sequence of cytochrome P450TYR and by exchanging the first eight
      codons with the first eight codons of bovine P45017 alpha. The highest yielding
      construct provided 200-500 nmol P450TYR/liter cell culture. The recombinant
      P450TYR was gently and efficiently extracted from E. coli spheroblasts by
      temperature-induced phase partitioning of Triton X-114 in the presence of 30%
      glycerol and isolated by DEAE and reactive red chromatography. In reconstitution
      experiments using saturating amounts of sorghum NADPH-cytochrome P450 reductase,
      the Km and turnover rate for isolated recombinant P450TYR was 0.22 +/- 0.06 mM
      and 49.2 +/- 3.8 min-1, respectively, whereas a turnover rate as high as 350 min
      1, was obtained using E. coli membranes. Addition of 3 mM glutathione stimulated
      the activity of reconstituted P450TYR and of sorghum microsomes although the
      effect was highly variable. Phenylalanine, the precursor of several cyanogenic
      glucosides, gave a type I binding spectrum, but was not metabolized by P450TYR,
      demonstrating the high substrate specificity of this P450. Administration of
      radioactively labeled p-hydroxyphenylacetaldoxime to E. coli cells, showed E.
      coli metabolized p-hydroxyphenylacetaldoxime independent of the expression of
      P450TYR.

PMID- 7574711
TI  - Mutations within subdomain II of the extracellular region of epidermal growth
      factor receptor selectively alter TGF alpha binding.
AB  - The interactions of epidermal growth factor (EGF) and transforming growth factor
      alpha (TGF alpha) with the epidermal growth factor receptor (EGFR) were examined
      by insertion mutagenesis of the receptor. Seventeen insertions were made
      throughout a construct containing only the extracellular domain. This truncated
      receptor (sEGFR) was secreted and had a dissociation constant similar to that of
      the full-length solubilized receptor. Receptors with insertions within subdomain
      III were not secreted. Two receptors with insertions at positions 291 and 474,
      which border subdomain III, have significantly decreased binding to both EGF and
      TGF alpha relative to wild type. This confirms previous work demonstrating that
      subdomain III forms the primary binding site for EGF and TGF alpha. Four of the
      mutants within subdomain II had a decreased binding to TGF alpha relative to wild
      type, but had wild type binding to EGF. These results suggest that a region
      within subdomain II may selectively regulate the binding of TGF alpha. Two
      receptors which contained insertions within subdomains II and IV, approximately
      equidistant from the center of subdomain III, bound twofold more ligand molecules
      than wild type receptor, with an affinity similar to that of wild type receptor.
      These findings suggest that insertion at these positions allows the access of
      more than one ligand molecule to the binding site.

PMID- 7574712
TI  - Cytochrome P450 catalyzed covalent binding of methoxychlor to rat hepatic,
      microsomal iodothyronine 5'-monodeiodinase, type I: does exposure to methoxychlor
      disrupt thyroid hormone metabolism?
AB  - The insecticide methoxychlor is estrogenic in birds and mammals and interferes
      with sexual development and reproduction, but it is not known whether this
      toxicity is due solely to its estrogenicity. We now have found that during
      hepatic, microsomal metabolism of [ring-14C]- or [3H-OCH3]methoxychlor, their
      metabolite primarily binds to iodothyronine 5'-monodeiodinase, type I (5'-ID1).
      The purified, radiolabeled protein reacted with antibodies against protein
      disulfide isomerase, isoform Q5, which is highly homologous to 5'-ID1. Sequencing
      of the radiolabeled tryptic peptide indicated that methoxychlor bound to cysteine
      372 or 375 or to lysine 376 of 5'-ID1. Treatment of rats with methoxychlor for 4
      days decreased hepatic, microsomal 5'-ID1 activity from 2.94 to 2.20 nmol/min-mg
      prot (P < 0.02). Since 5'-ID1 catalyzes thyroxine conversion to the biologically
      active triiodothyronine, these data suggest that methoxychlor may interfere with
      thyroid hormone metabolism. This may be an additional factor in its environmental
      toxicity.

PMID- 7574713
TI  - Glycine N-methyltransferase is a mediator of cytochrome P4501A1 gene expression.
AB  - Cytochrome P4501A1, the isozyme most closely approximating aryl hydrocarbon
      hydroxylase activity under conditions of induction, is thought to be regulated by
      several trans-acting factors, including the 4S polycyclic aromatic hydrocarbon
      binding protein; this protein has recently been identified as glycine N
      methyltransferase (Raha et al. (1994) J. Biol. Chem. 269, 5750-5756). Previous
      studies had shown that partially purified liver preparations containing the 4S
      binding protein interacted with 5'-flanking regions of the cytochrome P4501A1
      gene. Consequently, the ability of the 4S binding protein to serve as a mediator
      in the regulation of the cytochrome P4501A1 gene was investigated further.
      Introduction of an antisense 24-mer oligonucleotide to glycine N
      methyltransferase cDNA into rat hepatoma H4IIE cells by lipofectin resulted in a
      60% reduction in the benzo(a)pyrene-mediated induction of ethoxyresorufin-O
      deethylase activity and protein over the sense and scrambled antisense
      oligonucleotide controls. In addition, the antisense oligonucleotide caused a
      marked reduction in the steady-state level of cytochrome P4501A1 mRNA; no such
      effect was observed with the sense oligonucleotide. Introduction of GNMT
      polyclonal antibodies into H4IIE cells by a streptolysin-O permeabilization
      technique markedly reduced both benzo(a)pyrene-binding and benzo(a)-pyrene
      induced ethoxyresorufin-O-deethylase activities, but had no effect on 2,3,7,8
      tetrachlorodibenzo-p-dioxin induction. Collectively, these findings suggest that,
      in addition to the Ah (dioxin) receptor, glycine N-methyltransferase appears to
      be both a polycyclic aromatic hydrocarbon-binding protein and a mediator of the
      induction of the cytochrome P4501A1 gene by polycyclic hydrocarbons such as
      benzo(a)pyrene.

PMID- 7574714
TI  - Reaction of neprilysin (neutral endopeptidase) and thermolysin with cyclic
      peptides.
AB  - The reaction of neprilysin and thermolysin with a series of cyclic beta-turn
      peptides, varying in length from 6 to 14 residues, has been studied. All of the
      cyclic peptides bind to neprilysin with their affinity increasing from 113 microM
      for the 6-membered ring to 17 microM for the 14-membered ring. The 6-membered
      cyclic peptide was not hydrolyzed. However, kcat increased from 1.5 min-1 for the
      8-membered cyclic peptide to 148 min-1 for the 14-membered cyclic peptide. With
      thermolysin binding of the 6- or 8-membered cyclic peptides was not detected. The
      Km values for the 10-, 12-, and 14-membered cyclic peptides were all in the 100
      microM range. With thermolysin, kcat increased from 7 min-1 for the 10-membered
      cyclic peptide to 27,000 min-1 for the 14-membered cyclic peptide. Cyclic
      peptides were all cleaved at N-terminally directed sites. Modeling of the binding
      of a cyclic peptide, structurally similar to the 12-membered cyclic beta-turn
      peptide described above, into the active site of thermolysin shows that only half
      of the substrate makes contact with the enzyme and that only residues on one side
      of the peptide could fit into the active site. From these studies it is concluded
      that key factors which influence catalysis include not only peptide sequence, but
      the flexibility of the peptide and the orientation of the S'1 residue in a cyclic
      peptide.

PMID- 7574715
TI  - A pH-dependent allosteric transition in Ascaris suum phosphofructokinase distinct
      from that observed with fructose 2,6-bisphosphate.
AB  - Ascaris suum phosphofructokinase exhibits dramatic shifts in its circular
      dichroic spectra in the pH range 6 to 8. These shifts are quite distinct from
      those induced by the activators AMP and fructose 2,6-bisphosphate. Concomitant
      with these pH-induced spectral shifts, the enzyme also displays changes in its
      allosteric behavior. Inorganic ions such as K+, NH+4, SO4(2-), and PO4(3-) also
      cause CD-spectral shifts similar to those produced by a change in pH. Based on
      the evidence derived from gel filtration and sedimentation equilibrium studies,
      the observed CD-spectral shifts are interpreted as due to conformational changes
      in the enzyme tetramer rather than due to a change in its aggregation state.
      Further, since the pK value of 6.4 obtained from pH dependence of increase in
      ellipticity at 210 nm agrees very well with the pK value of 6.8 for the loss of
      ATP inhibition due to modification of a histidine residue (G. S. J. Rao, B. A.
      Wariso, P. F. Cook, and B. G. Harris (1987) J. Biol. Chem. 262, 14068-14073), it
      is concluded that a single histidine residue in the ATP-inhibitory site acts as a
      trigger for the structural changes accompanying ATP inhibition of the enzyme.
      This view is strongly supported by the observation that the enzyme desensitized
      to ATP inhibition by chemical modification of a histidine residue in the ATP
      inhibitory site shows absolutely no change in its CD spectrum in the pH range 6
      to 8. This study demonstrates that the mechanism of activation of
      phosphofructokinase at higher pH and by inorganic ions involves conformational
      transitions that are quite distinct from those induced by AMP and fructose 2,6
      bisphosphate. A scheme is presented that incorporates all of the different states
      of the enzyme dependent upon effectors and pH.

PMID- 7574716
TI  - Purification and characterization of porcine pepsinogen B and pepsin B.
AB  - Porcine pepsinogen B was prepared from extracts of adult porcine fundic mucosa.
      Immunoelectrophoresis showed no immunochemical cross-reactions between pepsinogen
      B and other porcine gastric zymogens. Pepsin B was purified after activation of
      the zymogen. The enzyme showed an optimum of general proteolytic activity at pH
      3.0. Activation of pepsinogen B at pH 2 resulted in formation of the covalent
      intermediate (pseudo-pepsin B) by proteolytic cleavage of bond Met16p-Glu17p (pig
      pepsinogen A numbering, "p" indicates residues of the prosegment peptide).
      Pseudopepsin B was stable at pH 2. The intermediate was converted to pepsin B at
      pH 5.5. The overall activation of pepsinogen B was much slower than found for
      other investigated gastric zymogens. During the conversion of pepsinogen B to
      mature pepsin B a segment of 43 amino acid residues was cleaved from the N
      terminal of pepsinogen B. The amino acid sequence of the prosegment and the first
      24 residues of pepsin B was determined. Relative to porcine pepsinogen A,
      progastricsin, and prochymosin, the following degrees of identities were
      observed: 40, 55, and 51%.

PMID- 7574717
TI  - Differential chemotactic responses mediated by platelet-derived growth factor
      alpha- and beta-receptors.
AB  - We have performed a modified Boyden chamber chemotaxis assay using NRK-49F cells
      under serum-free condition, in order to characterize the chemotactic activity of
      recombinant platelet-derived growth factor (PDGF)-AA, -AB, and -BB. All three
      PDGF isoforms showed similar chemotactic activity on NRK cells expressing both
      PDGF alpha- and beta-receptors. A checkerboard analysis revealed that PDGF-AA was
      a true chemoattractant for NRK cells, indicating that alpha-receptors could
      transduce signals for the chemotactic response. We then examined the inhibitory
      effects of PDGF isoforms in the upper chamber on NRK cell migration to PDGF in
      the lower chamber. When higher concentrations of PDGF-AB or -BB were present in
      the upper chamber, cell migration to any of the PDGF isoforms was completely
      blocked, whereas PDGF-AA in the upper chamber could not induce complete
      inhibition of the chemotactic migration to PDGF-AB or -BB. Even when 100 ng/ml of
      PDGF-AA was present in the upper chamber, NRK cell migration to 5 ng/ml of PDGF
      AB in the lower chamber was not completely blocked. These findings suggest that
      the chemotactic response induced by ligand binding to PDGF beta-receptor may be
      different from that induced by ligand binding to PDGF alpha-receptors.

PMID- 7574718
TI  - Fluorescence of a tryptophan bearing peptide from smooth muscle myosin light
      chain kinase upon binding to two closely related calmodulins.
AB  - We have investigated the fluorescence of a calmodulin binding peptide (AS19)
      based on the sequence of the calmodulin binding domain of smooth muscle myosin
      light chain kinase and bearing a tryptophan residue at position 5 upon binding to
      two closely related calmodulins. The emission maximum of peptide AS19 bound to
      the engineered SYNCAM calmodulin was 318 nm and a vibrational structure was
      clearly apparent. The emission maximum of peptide AS19 bound to chicken gizzard
      calmodulin (ChG CaM) was 327 nm and its spectrum was featureless. Red edge
      excitation effect supports the assumption that the polarity of Trp-5 environment
      is larger in the complex with ChG CaM than with SYNCAM, in agreement with
      fluorescence spectra. Time-resolved fluorescence and anisotropy measurements
      showed that, in both complexes, the tryptophan emitting state was 1La. The X-ray
      structure of the calmodulin-peptide complex has been resolved (W. E. Meador, A.
      R. Means, and F. A. Quiocho, 1992, Science 257, 1251-1255). The Trp binding site
      has been characterized. It differs by a single-point mutation between the two
      calmodulins: Met-144 of ChG CaM has been replaced by Val in SYNCAM. This suggests
      that the spectral relaxation of Trp-5 in the complex with ChG CaM as compared to
      SYNCAM is due to the polarizability of the sulfur atom containing Met side chain
      that is higher than that of Val. This provides an ideal system to investigate the
      origin of the Stokes shift of the indole moiety in proteins.

PMID- 7574719
TI  - Purification and characterization of taxa-4(5),11(12)-diene synthase from Pacific
      yew (Taxus brevifolia) that catalyzes the first committed step of taxol
      biosynthesis.
AB  - The first step in the biosynthesis of taxol in Pacific yew (Taxus brevifolia) is
      the cyclization of the universal diterpene precursor geranylgeranyl pyrophosphate
      to taxa-4(5),11(12)-diene. This parent olefin of the taxane diterpenoids is then
      elaborated to taxol and related compounds by a complex series of reactions
      involving oxidations and side-chain acylations. Cyclization activity is located
      principally in yew stem bark and adhering cambium. The operationally soluble
      cyclization enzyme was partially purified (approximately 600-fold) by combination
      of anion exchange, hydrophobic interaction, and dye-ligand chromatography.
      Nondenaturing, followed by denaturing, polyacrylamide gel electrophoresis, in
      combination with gel permeation chromatography, allowed the identification of
      taxadiene synthase as a monomeric protein of molecular weight 79,000. In general
      properties (divalent metal ion requirement, kinetic constants, molecular weight),
      the taxadiene synthase of Pacific yew is similar to the diterpene cyclase
      abietadiene synthase involved in resin acid biosynthesis in other gymnosperms.
      However, in pH optimum and response to inhibitors, these two diterpene cyclases
      are distinctly different. The activity (and enzyme protein) levels of Pacific yew
      taxadiene synthase are much lower than those for abietadiene synthase of
      lodgepole pine stem (constitutive) or of grand fir stem (wound-inducible) and the
      enzyme is not inducible to higher levels by stem wounding or elicitor treatment.

PMID- 7574720
TI  - Identification of a topology control domain in the tetracycline resistance
      protein.
AB  - Two N-terminal fusion proteins combining Escherichia coli maltose-binding protein
      (MBP) and the 12-transmembrane-segment pBR322 tetracycline resistance protein
      (Tet) have been constructed to determine the strength and location of topology
      control signals within the N-terminal portion of the Tet protein. The fusions
      contain either a secretable (wild-type) or a nonsecretable (MBP delta 2-26) MBP
      domain joined to the normally cytoplasmic N-terminus of the Tet protein. The
      effects of MBP targeting on Tet topology were investigated by analyzing the
      susceptibility of fusion strains to tetracycline and by proteolysis of the fusion
      proteins in inverted membrane vesicles and spheroplasts. The fusion protein
      containing MBP delta 2-26 conferred tetracycline resistance to the host strain
      and gave a normal pattern of Tet digestion fragments, indicating that its Tet
      domain is oriented and folded properly in the membrane. In contrast, the fusion
      containing secretable MBP was catalytically inactive apparently due to transfer
      of the Tet N-terminus to the periplasm with MBP. However, protease treatment of
      this fusion revealed that MBP secretion seems to affect only the topology of
      segments 1 and/or 2 of the Tet domain. Therefore, a strong topology control
      sequence appears to be located in the first cytoplasmic loop of the protein.

PMID- 7574721
TI  - Manganese content and high-affinity transport in liver and hepatoma.
AB  - Morris hepatomas 3924A and 9618A have much lower endogenous contents of Mn than
      normal rat liver. This work studied the uptake of Mn by slices of these three
      tissues over a range of concentrations from 0.05 to 100 microM. The influx was
      assessed with 54Mn while atomic absorption measurements determined the total
      content. At medium Mn from 0.05 to 5 microM, entry of 54Mn in 2 min was taken as
      the initial rate and within this period the apparent concentration of Mn in the
      cell water exceeded that in the medium. Liver showed three apparently saturable
      uptake systems, the medium concentrations of Mn for half-maximal uptake rate
      being 0.075, approximately 2, and 100 microM. Hepatoma 3924A appeared to have
      only two systems, the half-maximal concentration for the higher affinity
      mechanism being, at 0.34 microM, substantially greater than that for liver. At no
      concentration was the uptake rate of Mn by hepatoma 3924A less than that of liver
      although there was some indication that Mn uptake by 9618A was somewhat less than
      that by the other two tissues. It is concluded that liver and hepatoma 3924A have
      systems for Mn uptake with affinities that enable them to be active at the plasma
      concentration (approximately 0.1 microM) as well as uptake systems of less
      affinity. However, differences in these systems between liver and hepatomas do
      not account for the differences in endogenous Mn content.

PMID- 7574722
TI  - Cloning and expression of a rat liver phenobarbital-inducible UDP
      glucuronosyltransferase (2B12) with specificity for monoterpenoid alcohols.
AB  - A full-length cDNA, HBPA2, that encodes for a new rat hepatic UDP
      glucuronosyltransferase protein, designated UGT2B12, was isolated from a rat
      liver cDNA library. The isolated clone contains a 1590-nucleotide open reading
      frame flanked by 2 and 252 base pairs of 5' and 3' noncoding sequences,
      respectively. Human embryonic kidney 293 cells transfected with UGT2B12 expressed
      a protein with a subunit molecular mass of 53 kDa. The expressed protein
      catalyzed the glucuronidation of monoterpenoid alcohols, such as (-)-borneol, (+)
      menthol, and (-)-nopol. In addition, a number of simple phenolic compounds, such
      as hydroxybiphenyls, 7-hydroxylated coumarins, p-nitrophenol, and food-derived
      substances (e.g., naringenin and eugenol), were also substrates for the expressed
      enzyme. Northern blot analysis showed that treatment of rats with phenobarbital
      increased hepatic mRNA levels for UGT2B12 approximately twofold. In addition to
      liver, Northern blot analysis demonstrated that UGT2B12 mRNA is present in kidney
      and testis.

PMID- 7574723
TI  - Carboxy-terminal truncation of oryzacystatin II by oryzacystatin-insensitive
      insect digestive proteinases.
AB  - The biochemical interactions between digestive proteinases of the Coleoptera pest
      black vine weevil (Otiorynchus sulcatus) and two plant cysteine proteinase
      inhibitors, oryzacystatin I (OCI) and oryzacystatin II (OCII), were assessed
      using gelatin-polyacrylamide gel electrophoresis, OCI-affinity chromatography,
      and recombinant forms of the two plant inhibitors. The insect proteinases were
      resolved in gelatin-containing polyacrylamide gels as five major bands, only
      three of them being totally or partially inactivated by OCI and OCII. The maximal
      inhibitory effect of both OCs at pH 5.0 was estimated at 40% and the inhibition
      was stable with time despite the presence of OC-insensitive proteases, indicating
      the stability of the OCI and OCII effects. After removing OC-sensitive
      proteinases from the insect crude extract by OCI-affinity chromatography, the
      effects of the insect cystatin-insensitive proteases on the structural integrity
      of the free OCs were analyzed. While OCI remained stable, OCII was subjected to
      limited proteolysis leading to its gradual transformation into a approximately
      10.5-kDa unstable intermediate, OCIIi. As shown by the degradation pattern of a
      glutathione S-transferase (GST)/OCII fusion protein, the appearance of OCIIi
      resulted from the C-terminal truncation of OCII. Either free or linked to GST,
      OCIIi was as active against papain and human cathepsin H as OCII, and the initial
      specificities of the inhibitor for these two cysteine proteinases were conserved
      after cleavage. Although these observations indicate the high conformational
      stability of OCII near its active (inhibitory) site, they also suggest a general
      conformational destabilization of this inhibitor following its initial cleavage,
      subsequently leading to its complete hydrolysis. This apparent susceptibility of
      OCII to proteolytic cleavage by the insect proteinases could have major
      implications when planning the use of this plant cystatin for insect pest
      control.

PMID- 7574724
TI  - The length of 5'-untranslated leader sequences influences distribution of 3
      hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in polysomes: effects of
      lovastatin, oxysterols, and mevalonate.
AB  - Transcripts for hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      are heterogeneous in length. This heterogeneity is due to variations in the
      length of 5'-untranslated leader (UTL) sequences, which are generated by both
      alternate splicing within the first exon as well as alternate transcription start
      sites. Because mRNA 5'-UTL sequences have a role in regulating translational
      efficiency, the level and distribution of HMG-CoA reductase transcripts were
      measured in both total cellular RNA and polysomes from the Syrian hamster cell
      line C100. Cells were treated with either lovastatin alone, lovastatin and 25
      hydroxycholesterol (25-OH C), or lovastatin, 25-OH C, and mevalonate, three
      treatment regimens used in an earlier study to demonstrate nonsterol-mediated
      translational control of HMG-CoA reductase synthesis [D. M. Peffley (1992) Somat.
      Cell Mol. Genet. 18, 19-32]. When reductase mRNA was measured by 5'-extension
      analysis under the same conditions, levels of transcripts with 5'-UTL regions
      ranging from 41 to 81 bases were reduced approximately four- to eightfold. In
      contrast, transcripts with 5'-UTL regions 93 to 100 bases in length were not
      reduced, and transcripts with 5'-UTL regions approximately 300-400 bases in
      length increased twofold. The addition of 25-OH C alone or both 25-OH C and
      mevalonate to lovastatin-treated cells lowered HMG-CoA reductase mRNA levels
      fivefold in total cellular RNA as determined by RNase protection assay. No
      comparable change was observed with control ribosomal protein S17 mRNA.
      Postmitochondrial supernatants representing both translationally inactive
      monosomes and translationally active polysomes were prepared by sucrose gradient
      fractionation from cells incubated with the standard three treatments. Because 5'
      UTL sequences of many mRNAs have a role in regulating translational efficiency we
      isolated RNA from each fraction and measured levels of reductase transcripts by
      5'-extension analysis. Under all three conditions, transcripts with 5'-UTL
      sequences 41-103 bases in length were primarily associated with dense sucrose
      fractions that contain polysomes. In contrast, reductase transcripts with leader
      sequences 300 to 400 bases were almost exclusively associated with the less dense
      sucrose fractions containing monosomes. These results indicate that both the
      level and polysome distribution of individual reductase transcripts are
      influenced by the length of 5'-UTL sequences.

PMID- 7574725
TI  - Interactions of tubulin with guanine nucleotides that have paclitaxel-like
      effects on tubulin assembly: 2',3'-dideoxyguanosine 5'-[alpha,beta
      methylene]triphosphate, guanosine 5'-[alpha,beta-methylene]triphosphate, and
      2',3'-dideoxyguanosine 5'-triphosphate.
AB  - Despite reduced affinity for the exchangeable nucleotide binding site of tubulin
      relative to GTP, 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) and guanosine 5'
      [alpha, beta-methylene]triphosphate [pp(CH2)pG] are highly active in promoting
      tubulin assembly. Like the antimitotic drug paclitaxel, which interacts with the
      same part of the beta-tubulin molecule as exchangeable-site GTP, both analogs
      enhance nucleation reactions and promote formation hyperstable polymers. These
      observations led us to synthesize the doubly modified analog 2',3'
      dideoxyguanosine 5'-[alpha, beta-methylene]triphosphate [pp(CH2)pddG]. We
      compared the effects of pp(CH2)pddG to those of ddGTP, pp(CH2)pG, and the three
      cognate diphosphates in their interactions with tubulin. We found that
      pp(CH2)pddG was as active as ddGTP and pp(CH2)pG in supporting formation of
      polymer of increased stability, but that its affinity for the exchangeable site
      was lower than that of both singly modified analogs [relative affinities for the
      exchangeable site for pp(CH2)pddG:ddGTP:pp(CH2)-pG:GTP were 1:2.8:10:273]. There
      were significant differences in interactions of each of the three analogs with
      tubulin, and the behavior of pp(CH2)pddG was intermediate between that of ddGTP
      and that of pp(CH2)pG. Most importantly, under the reaction conditions studied,
      with heat-treated microtubule-associated proteins (MAPs) ddGTP-induced polymer
      consisted of short microtubules, while polymer formed with both pp(CH2)pddG and
      pp(CH2)pG consisted of short sheets. On the other hand, assembly without MAPs had
      a fivefold lower critical concentration for tubulin with ddGTP and pp(CH2)pddG
      (0.5 mg/ml) than with pp(CH2)pG (2.5 mg/ml). De novo assembly, which occurs
      readily with 2',3'-dideoxyguanosine 5'-diphosphate, was not observed with either
      alpha, beta-methylenediphosphate GDP analog.

PMID- 7574726
TI  - Peroxynitrite causes DNA damage and oxidation of thiols in rat thymocytes
      [corrected].
AB  - We report here the ability of peroxynitrite to cause DNA strand breaks and to
      oxidize cellular thiol groups in viable rat thymocytes. Peroxynitrite was added
      to rat thymocytes in a phosphate buffer and DNA damage was measured by the
      fluorescence analysis of DNA unwinding assay. Peroxynitrite causes DNA strand
      breaks in a dose-dependent fashion. Four hydroxyl radical scavengers, namely
      mannitol, dimethyl sulfoxide, sodium benzoate, and Trolox, were tested for their
      ability to protect DNA from oxidative damage by peroxynitrite. Mannitol failed to
      protect DNA at concentrations at which it would have conferred nearly complete
      protection from damage by the hydroxyl radical. Strikingly, dimethyl sulfoxide
      and benzoate, which are more efficient hydroxyl radical scavengers than mannitol,
      caused an increase in DNA damage. Trolox was the only scavenger, among the four
      tested here, that was able to protect DNA from oxidative damage by peroxynitrite.
      We have previously shown that, among the scavengers tested, Trolox is the most
      effective scavenger of HOONO*, where HOONO* is a reactive form of HOONO that is a
      more selective oxidant than is the hydroxyl radical (see W. A. Pryor, X. Jin, and
      G. L. Squadrito, 1994, Proc. Natl. Acad. Sci. USA 91, 11173-11177). Thus, these
      results are consistent with our earlier observations that oxidations by
      peroxynitrite involve a reactive intermediate, HOONO*, rather than hydroxyl
      radicals. Peroxynitrite also oxidized cellular thiols in a dose-dependent
      fashion. Greater than 90% of the cells exposed to peroxynitrite were still viable
      for up to 10 min after DNA damage and thiol oxidation had occurred. In
      conclusion, DNA damage caused by peroxynitrite can be rationalized as caused by a
      powerful oxidant, HOONO*, which is formed during the decomposition of
      peroxynitrite to nitrite.

PMID- 7574727
TI  - The nuclear prolactin receptor: a 62-kDa chromatin-associated protein in rat Nb2
      lymphoma cells.
AB  - Previously we demonstrated that lactogen-dependent Nb2 cells express a nuclear
      prolactin (PRL) receptor. Thus, the nuclear receptor expressed in PRL-dependent
      Nb2-11 and -independent Nb2-SFJCD1 cells was characterized. Initially, the
      potential proteolytic processing of internalized 125I-rPRL was investigated.
      Radiolabeled hormone eluted from a Sephadex G-100 column with a retention time
      identical to that found for stock hormone, indicating that nuclear PRL was
      intact. Experiments to investigate the nuclear distribution of the hormone
      demonstrated that 90% of 125I-rPRL bound to chromatin; the remaining was
      distributed between "sap-protein" and nucleoplasmic fractions. Chromatin-bound
      PRL was resistant to high salt and detergent extraction indicating a tight
      association. Immunoprecipitation and immunoblot analysis revealed the PRL
      receptor to be 62 kDa in each cell line. Affinity crosslinking experiments and
      immunoprecipitation demonstrated that 125I-rPRL complexed with a protein(s) of
      similar M(r) in intact cells. 125I-rPRL binding was saturable and of high
      affinity (Kds of 180 and 170 pM, for Nb2-11 and Nb2-SFJCD1 lines, respectively).
      PRL binding was competitively inhibited by ovine and bovine PRLs and hGH, but not
      by rat GH, and by monoclonal antibodies (McAbs) which recognize the lactogen
      binding site. These results demonstrate that: (1) 125I-rPRL translocates intact
      to the Nb2 cell nucleus and tightly associates with chromatin; (2) the chromatin
      receptor specifically binds 125I-rPRL with high affinity; and (3) the chromatin
      receptor is essentially identical to its membrane counterpart with respect to
      mass, binding characteristics, and McAb recognition.

PMID- 7574728
TI  - Ethanol and isopentanol increase CYP3A and CYP2E in primary cultures of human
      hepatocytes.
AB  - In primary cultures of human hepatocytes prepared from three separate livers,
      ethanol increased both CYP3A and CYP2E1, as detected immunochemically.
      Isopentanol, the major higher chain alcohol in alcoholic beverages, also induced
      CYP3A and CYP2E1. Maximal increases in these P450s occurred at the lowest
      concentrations of isopentanol examined, 0.1 mM. Ethanol and isopentanol were each
      more potent and more effective at inducing CYP3A in the human hepatocytes than
      was previously shown in cultured rat hepatocytes. Steady-state levels of CYP3A3/4
      mRNA were increased by both ethanol and isopentanol. Ethanol and isopentanol
      induced immunoreactive CYP3A to a greater extent than did phenobarbital. In all
      three cultures, the increases in CYP3A after treatment with ethanol were less
      than those observed after treatment with rifampicin, a highly effective inducer
      of CYP3A in human hepatocytes. In one human hepatocyte culture, the lowest
      concentration of isopentanol tested increased CYP3A protein to an amount similar
      to that increased by rifampicin. In another human hepatocyte culture, however,
      the amount of immunoreactive CYP3A increased by isopentanol was less than that
      increased by rifampicin. In this latter culture, the steady-state levels of
      CYP3A3/4 mRNA increased by 0.1 mM isopentanol and 1 microM rifampicin were
      similar. This is the first finding of induction of CYP3A in human hepatocytes by
      ethanol or isopentanol. The clinical significance of the findings is discussed.

PMID- 7574729
TI  - Update on regional treatments for hepatobiliary malignancies.

PMID- 7574730
TI  - [Cancer-pain management in home care].
AB  - Patient was 58 year old female with severe uterus cancer pain who refused to take
      the oral morphine in hospital because doctor should be hesitated to discharged
      patient whose pain is particularly difficult to manage in home. A few days later,
      she returned back home with her family irritably and recovered from hallucination
      by morphine-intake in home. The oral morphine is the prepared route of analgesic
      administration in home care. When patient can not take medications orally,
      continuous intravenous infusion provides the most consistent level of analgesia.
      In future, transdermal route offers a practical alternative in the hospice and
      home.

PMID- 7574731
TI  - [Intra-arterial 5-FU/intra-venous MTX therapy for metastatic liver lesions].
AB  - We have performed intra-arterial 5-fluorouracil (5-FU)/intra-venous methotrexate
      (MTX) therapy for 4 patients with multiple metastatic liver tumors at out-patient
      clinic. Primary lesions were of the stomach (one patient, synchronous) and colon
      (3 patients, two were synchronous and one was metachronous). 5-FU (250-350
      mg/day) was continuously infused for two weeks into the hepatic artery through
      the reservoir using the Baxter Infuser (multi-day type). MTX (100 mg/m2) was
      infused into the peripheral vein on days 1, 8 and 15. Leucovorin calcium (15 mg)
      was orally administered three times after MTX infusion. All patients partially
      responded, and no remarkable side effect was detected. We propose that this new
      combination therapy, that is intra-arterial 5-FU and intra-venous MTX for
      metastatic liver cancer, can be useful and safe even for out-patients.

PMID- 7574732
TI  - [A new modality of locoregional chemotherapy based on biochemical double
      modulation of 5-fluorouracil with both leucovorin and cisplatin against liver
      metastases of colorectal cancer].
AB  - A new modality of locoregional chemotherapy based on biochemical double
      modulation of 5-fluorouracil (FU) with both leucovorin (LV) and cisplatin (CDDP)
      against liver metastases of colorectal cancer was devised. The schedule for the
      locoregional therapy was as follows; bolus infusion of LV (6 mg/body) followed by
      30-minute infusion of CDDP (10 mg/body) and 30-minute infusion of 5-FU (250
      mg/body). Four colorectal cancer patients with numerous metastases to both lobes
      of liver were given intraarterial administration of above anticancer drugs every
      1-2 weeks after resection of primary lesions. On the one hand, 3 colorectal
      cancer patients, who developed a few metastases to both lobes of liver, were
      treated preventively by the same schedule every 2-3 weeks after the resection of
      metastatic tumors. As for the clinical (radiographic) response, complete response
      and partial response were observed in 1 and 2 of 4 patients, respectively. The
      response rate was 75%. No new lesions appeared for over 1 year by the preventive
      treatment in 2 of 3 patients, whereas new lesions appeared in one patient at 3
      months after discontinuation of treatment because of mild toxicity. The toxicity,
      however, was within acceptable limits. These results indicated that biochemical
      double modulation of 5-FU with both LV and CDDP is a very promising locoregional
      chemotherapy against liver metastases of colorectal cancer.

PMID- 7574733
TI  - [Study on therapeutics adopted after occlusion of intraarterial reservoir in
      patients with liver tumor].
AB  - Over the last 5 years, we experienced thirty-nine patients with liver tumors
      undergoing implantation of an intraarterial reservoir through the gastroduodenal
      artery. Nine of the 39 patients had hepatocellular carcinomas, while the rest had
      metastatic liver tumors. In 32 patients, intraarterial chemotherapy via an
      implanted reservoir was discontinued either because of death in 20 patients with
      an average survival period of 11.7 months or because of occlusion of an
      intraarterial line in 12 patients with an average treatment period of 20.2
      months. Regarding treatment modalities adopted for intraarterial therapy,
      transcatheter arterial embolization, surgical resection, microwave tumor
      coagulation, ethanol injection therapy, and a subselective intraarterial
      chemotherapy were performed in 3 patients with hepatocellular carcinomas. All of
      them survived more than 2 years after disuse of the reservoir. Out of 5 patients
      with metastatic liver tumors of colorectal cancer, one patient underwent
      additional surgical resection, two patients had no therapy who survived only two
      or three months, and two patients were still alive without additional therapies.
      Of four patients with metastatic liver tumors, 3 from breast cancer and one from
      leiomyosarcoma of stomach were treated with systemic chemotherapy or subselective
      intraarterial chemotherapy combined with radiation therapy. The average survival
      period of these 12 patients was 16.2 months, and 7 of them are still alive.

PMID- 7574734
TI  - [Complications in the intraperitoneal chemotherapy with the implantable
      intraperitoneal port and the strategy for the prevention of the complication].
AB  - Fifty-four patients with gastrointestinal carcinomas were treated with
      intraperitoneal chemotherapy through devices, and an implantable port system
      which had been used subcutaneously. The complications of the implantable ports
      were analysed in this study. There were 1 bowel perforation, 2 cases of retention
      of ascites, 2 infections, 2 inflow obstructions and 8 cases of pain, especially
      in the perineal or lower abdominal area. The number of patients requiring removal
      of the device due to complications were 7; 1 perforation, 2 ascites, 2 infections
      and 2 for pain. The strategy for reducing the complications due to the device
      were analysed as follows. A soft catheter should be selected. The catheter in the
      abdominal cavity should not be long, not as long as the tip of catheter touch the
      bottom of pelvic organs. Due care for kinking of the catheter should be taken in
      the implanting procedure. Antibiotics should be applied in and around the port.
      Steroids should be added to the solution for intraperitoneal chemotherapy.

PMID- 7574735
TI  - [Pharmacokinetic study of intraperitoneally administered plachitin for non
      curative gastrointestinal cancer].
AB  - Plachitin is a chemical compound of cis-diammine-dichloroplatinum (CDDP) and
      chitin. Pharmacokinetics and adverse effects of Plachitin for intraperitoneal
      chemotherapy (IP) were studied in 11 patients who suffered from non-curative
      gastrointestinal cancers in comparison with 4 patients who underwent IP of CDDP.
      Five patients were given 300 mg (100 mg as CDDP) of Plachitin which was cotton
      type on the residual cancer mass (Group A). Six patients were given IP 300 mg of
      Plachitin particles (Group B). As the control group, 4 patients were given IP 100
      mg of CDDP (Group C). The platinum concentrations of serum, urine and
      intraperitoneal discharge were observed during 3-4 weeks after the treatments and
      calculated as the CDDP concentration. The serum CDDP levels were below 0.1
      micrograms/ml for 4 weeks in Group A and B. In Group A, urine concentrations of
      CDDP were significantly lower than in Group B and C at 3 and 5 days after the
      treatment statistically (p > 0.05). But at 14 days after treatment, the urine
      concentration of CDDP in Group A was higher than in Group C. In Group A and B,
      the CDDP concentrations of intraabdominal discharge was lower than in Group C
      statistically (p > 0.05). Nausea was observed only in one patient of Group B and
      other adverse effects which contained renal sufficiency were not recognized in
      the three groups. Thus, Plachitin was considered an effective and safe agent for
      intraperitoneal chemotherapy.

PMID- 7574736
TI  - [Effects of angiogenesis inhibitor TNP-470 to suppress the recurrence in the
      liver remnant after partial hepatectomy for liver metastases in rabbits].
AB  - We investigated the effects of an angiogenesis inhibitor, TNP-470, in suppressing
      the recurrence in the liver remnant after partial hepatectomy for VX2 liver
      metastases model of rabbits. After inoculation of 1 x 10(6) VX2 tumor cells via
      the portal vein, the medial lobe of the liver was resected. Then, TNP-470 (7
      mg/body/day) was infused (Group 1), or distilled water (Group 2), continuously
      via the mesenteric vein for a week. The control group received only infused
      distilled water via the mesenteric vein. Fourteen days after the tumor
      inoculation, there were 66.0 +/- 20.2 (mean +/- SD) metastatic colonies on the
      liver surface of control group, against 23.3 +/- 24.0 and 123.7 +/- 47.9 colonies
      in Group 1 and Group 2, respectively. There were significant differences between
      control group and Group 2, and between Group 1 and Group 2. We consider that the
      liver regeneration following hepatectomy might provoke tumor growth of occult
      metastases in the liver remnants. TNP-470 suppressed these growth by its anti
      neovascular activity. And this effect reduced the number of metastatic colonies.
      Fourteen days after hepatectomy, the weights of the liver were no different among
      3 groups. The BrdU Labeling Index was also no different between Group 1 and Group
      2. TNP-470 did not suppress the regeneration of the liver remnant. We consider
      that the systemic side effects of TNP-470 might be made minimal, because this
      agent affects only on endothelial cells. These results suggest that the
      angiogenesis inhibitor TNP-470 is beneficial to suppress hepatic recurrence after
      partial hepatectomy for liver metastases without suppression of liver
      regeneration.

PMID- 7574737
TI  - [Suppression of postoperative liver metastases from colon cancer by continuous
      intraportal infusion of an angiogenesis inhibitor FR-118487].
AB  - A rabbit VX2 colon cancer model with spontaneous liver metastases was used to
      evaluate the antitumor effect of an angiogenesis inhibitor, FR-118487. FR-118487
      (1 mg/kg/day) was infused continuously into the portal vein for a week after
      resection of primary colon cancer lesions (FR group). The incidence of liver
      metastases was 71.4% (5/7) in FR group, and 100% (7/7) in control group. The
      number and the weight of liver metastatic nodules were 31.0 +/0 36.0 and 1.4 +/-
      1.8 g in FR group versus 83.7 +/- 73.9 and 6.5 +/- 4.9 g in control group,
      respectively. The metastases in FR group were significantly decreased in weight
      compared with those in control group (p < 0.05). No anastomotic leakage was
      recognized in either group. No side effects of FR-118487 such as body weight loss
      were found. Continuous intraportal infusion of FR-118487 in the early
      postoperative period may be effective to suppress liver metastases from colon
      cancer by inhibiting the angiogenesis concerning liver metastases.

PMID- 7574738
TI  - [Postoperative adjuvant arterial infusion chemotherapy in patients with advanced
      hepatocellular carcinoma].
AB  - Seventy-five surgically treated patients with hepatocellular carcinoma (HCC) of
      Stage III or IV-A were divided into two groups: group I, control without
      postoperative adjuvant infusion (PAI); group II, patients treated with PAI. In
      the PAI group, 29 patients (mean diameter of tumors = 71 mm) prophylactically
      underwent PAI after hepatic resection. Chemotherapeutic agents, (5-FU, ADM, MMC,
      CDDP and Lipiodol) were administered 4 times a year via the hepatic artery
      through Infuse A port. The remaining 46 patients (mean diameter of tumors = 70
      mm) served as the historical control without PAI. The 4-year cumulative survival
      rate was higher in the PAI group (45.6%) than in the control (25.4%, p = 0.0424).
      The 4-year disease-free survival rate was also improved in the PAI group (37.0%)
      compared with that in the control (14.4%, p = 0.0096). Intrahepatic multiple
      recurrence was recognized in 8 out of 29 patients in the PAI group (28%) and in
      24 out of 46 in the control (53%, p = 0.036) within 1 year after surgery.
      Extrahepatic recurrence without diseases in the remnant liver tended to occur
      with higher frequency in the PAI group than in the control. Based on our data, we
      suggest that PAI is effective in alleviating intrahepatic multiple recurrence
      within 1 year after hepatic resection for advanced HCC and that systemic
      chemotherapy may be necessary for preventing extrahepatic recurrence.

PMID- 7574739
TI  - [The effect of percutaneous hepatic venous isolation and charcoal hemoperfusion
      for high-dose chemotherapy for hepatoma].
AB  - We herein report the efficacy of percutaneous high-dose chemotherapy under
      hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) in the treatment of
      hepatoma patients. This study included 23 patients with bilobar multiple
      intrahepatic metastases and 1 patient with high risk for recurrence after
      hepatectomy. All patients received adriamycin at doses ranging from 60-150 mg/m2
      through the hepatic artery. Sixteen patients had HVI.CHP by the double-balloon
      technique, while a recent 8 patients had the single catheter technique using a
      4L.2B catheter; 4 of these 8 patients had repeated treatment. Except for two
      early patients with hepatic arterial thrombosis and necrotizing pancreatitis,
      there was no lethal complication, and quality of life after treatment was
      remarkably improved in patients treated by the single catheter technique. Among
      22 evaluable patients, 3 had CR and 11 had PR, yielding a response rate of 63%.
      Mean survival duration was prolonged to 13 months in responders, against only 5
      months in nonresponders. In conclusion, HVI.CHP was highly effective for advanced
      hepatoma patients and the single catheter technique facilitated a repeated high
      dose intraarterial chemotherapy, which may offer a possibility of complete
      remission even in highly advanced cases.

PMID- 7574740
TI  - [Effects of adjuvant surgical therapy for continuous regional therapy for
      advanced hepatocellular carcinoma].
AB  - In order to repeat the effective transarterial embolization (TAE) or regional
      chemotherapy, adjuvant surgical therapies were performed for 25 patients with
      advanced hepatocellular carcinomas (HCC) having collateral feeders. The
      procedures involved the reduction of tumors with collateral feeders, permanent
      decollateralization using silicone rubber sheeting of the liver (WRAP therapy),
      and combination therapies. The 1-, 3- and 5-year survival rates of the patients
      after the adjuvant surgery were 67%, 18% and 5%, respectively. The 3- and 5-year
      survival rates of the patients after the initial TAE or arterial chemotherapy
      were 57% and 12%, respectively. On the other hand, the 3- and 5-year survival
      rates of patients who had TAE alone (n = 443) were 29% and 14%, respectively.
      Consequently, this adjuvant surgical therapy may be a useful palliative treatment
      for HCC.

PMID- 7574741
TI  - [Preventive chemotherapy for residual liver after resection of hepatic metastasis
      from colorectal cancer].
AB  - We compared 12 cases treated with intra-arterial chemotherapy (group A), with 15
      cases only undergoing the usual hepatectomy (June 1991-February 1995). Six cases
      in group A were H1, 4 were H2, and 2 were H3; 12 cases in group B were H1, and 3
      were H2. In both groups, primary lesions were removed. All cases received high
      dose intermittent 5-FU infusion (WHF) at 1,000 mg/m2 via a reservoir for 5 hours
      a week at the outpatient clinic. Cumulative survival rates for 1 and 3 years are
      100% and 68.6%, respectively, in group A, and 58.7% and 25.2% in group B, which
      indicates the treatment outcome in group A was significantly better. Recurrence
      in residual liver was not found in group A except for one case whose tumor was
      unremoved, but it was found in 8 cases (53.3%) in group B up to this writing. CEA
      value after resection in group A was within the normal range except for one case
      with a local recurrence. It seems that intra-arterial 5-FU infusion chemotherapy
      for residual liver after resection of hepatic metastasis from colorectal cancer
      has a preventive effect on residual liver, and the improvement of the cumulative
      survival rate can be expected.

PMID- 7574743
TI  - [Evaluation of prophylactic hepatic arterial infusion chemotherapy after
      hepatectomy for metastases from colorectal cancer].
AB  - The significance of continuous hepatic arterial infusion (HAI) chemotherapy of 5
      FU to prevent recurrence in the remnant liver following curative hepatectomy for
      colorectal metastases was analyzed in the prospective randomized study. Patients
      of HAI chemotherapy group received 6 weeks of 5-FU 500 mg/day. The one- and two
      year overall survival rates of nine patients with HAI therapy were 87.5% and
      87.5%, respectively, while the rates of ten cases without the regional
      chemotherapy were 100% and 66.7%, respectively, indicating no obvious difference.
      On the other hand, the disease-free survival rates of HAI Group were higher than
      those of control group. The disease-free survival rates of the former were 75.0%
      at one-year and 75.0% at two-year, and the rates of the latter were 47.6% and
      47.6%, respectively. No serious complications such as severe liver dysfunction,
      sclerotic cholangitis or hepatic necrosis were observed. Although the follow-up
      period was not enough long to accurately evaluate the efficacy, local
      prophylactic chemotherapy by continuous infusion of 5-FU could be a promising
      method as an adjuvant chemotherapy after hepatic resection for colorectal
      metastases.

PMID- 7574742
TI  - [Study of hepatic arterial infusion chemotherapy for prophylaxis of liver
      metastases of colorectal cancer after hepatic resection].
AB  - We examined the significance of hepatic arterial infusion chemotherapy (HAIC) for
      prophylaxis of liver metastases of colorectal cancer after hepatic resection
      using an implantable port. Fifty-five patients operated at the hospital from
      August 1988 to December 1994 were divided into two groups consisting of 23
      patients with HAIC group: (HAIC (+)), and 32 patients without HAIC group: (HAIC (
      )) retrospectively. The cumulative survival rates and recurrent rates of cancer
      free in remnant liver of HAIC (+) were improved, compared with HAIC (-). This
      suggests that HAIC was effective in improving the prognosis and preventing
      recurrence in remnant liver.

PMID- 7574746
TI  - [Advantages and disadvantages of the intraarterial chemotherapy using a reservoir
      as postoperative adjuvant therapy for hepatocellular carcinoma].
AB  - We conducted a retrospective study on the efficacy and disadvantages of
      intraarterial chemotherapy using a reservoir (ICUR), as postoperative adjuvant
      therapy for hepatocellular carcinoma (HCC). One hundred and seventy HCC patients
      who underwent hepatectomy since 1987 to 1992 in our institute were enrolled in
      this study. Ninety-two patients were postoperatively treated with ICUR (group R),
      and seventy-eight patients without it (group N). There were no significant
      differences between the two groups in the preoperative evaluations of the
      characteristics of patients, tumors, and operative procedures. Although
      statistical significances were not found, disease-free rates within 1 year and
      cumulative survival rates appeared to be higher in group R than in group N.
      Patency of the catheter of reservoirs at one and two years were maintained in
      80.3 and 44.1% of the patients, respectively. HCC recurred after an occlusion of
      the reservoir in 18 patients. In four out of these 18 patients, transcatheter
      arterial embolization (TAE) for recurrent tumors was not feasible, because of
      occlusion of the hepatic artery. TAEs for recurrent lesions would have been
      impossible in about 10% of all patients treated with ICUR. Thus, both the
      advantages and disadvantages should be taken into consideration on the indication
      of ICUR, and the maintainance of the catheter is important for successful ICUR.

PMID- 7574745
TI  - [The study of continuous arterial infusion chemotherapy with CDDP and 5-FU in
      patients with hepatocellular carcinoma].
AB  - Between Feb. 1992 and April in 1995, 22 patients with hepatocellular carcinoma
      (10, recurrence; 12, unresectable) received continuous arterial infusion of CDDP
      and 5-FU via implanted reservoir. For the next five days, 10 mg/body of CDDP and
      250 mg/body of 5-FU using arterial infusion were administered. It was
      discontinued for two days as one course, and 4 courses were basally administered.
      Patients were divided into 2 groups (6 hours group and 24 hours group) according
      to the duration of the administration of 5-FU. There were no differences in
      efficacy rate between the 2 groups (6 hours group, 64%; 24 hours group, 62.5%),
      but CR (complete response) cases appeared in only the 6 hours group. There were
      no severe side effects in the 2 groups, but systemic side effects appeared in 6
      hours group more often than in 24 hours group. Only in the 24 hours group, 2
      patients had the narrowing and obstruction of hepatic artery which was suggested
      to be caused by intimal injury due to continuous administration of 5-FU.
      Continuous arterial infusion chemotherapy with CDDP and 5-FU seemed to be
      effective. Further study on adequate time and volume of administration including
      pharmacokinetics is needed to enhance the clinical effectiveness of continuous
      arterial infusion of CDDP and 5-FU.

PMID- 7574744
TI  - [Changes in CT-scan findings of liver metastases from gastric carcinoma treated
      by hepatic arterial infusion chemotherapy, especially after chemo-embolization
      and induced hypertensive chemotherapy].
AB  - The purpose of this study was to clarify the effectiveness of hepatic arterial
      infusion chemotherapy (HAIC) from not only the reduction rate but also the
      characteristic findings in CT-scan. Subjects were nine responders of HAIC for
      liver metastases from gastric carcinoma (chemo-embolization, 4 cases; induced
      hypertensive chemotherapy, 5 cases). Low density (LD), enhancement and
      indentation of the metastatic lesions were the characteristic findings. As the
      result, LD was more frequent in chemo-embolization cases (100%) than in induced
      hypertensive chemotherapy cases (60%). LD change, which was appeared in four
      cases before partial response, was one of the findings indicating the
      effectiveness. On the other hand, autopsy revealed severe LD to be necrosis or
      abscess of metastatic lesion. Therefore, we should pay attention to avoid
      complications such as rupture, and discontinue HAIC when severe LD appears.

PMID- 7574747
TI  - [Hepatic arterial infusion therapy for gastric liver metastasis using implanted
      reservoir].
AB  - Gastric liver metastasis is a fatal disease, and there is no golden standard as
      to its therapeutic mode. We experienced 58 such cases. Liver resections were
      performed in six cases (Group 1). Hepatic arterial infusion (HAI) chemotherapy,
      with 500 mg 5-FU and 100 mg of carboplatin as one shot weekly, was performed in
      fifteen cases (Group 2). The 50% survival was 656 days for Group 1, and 565 days
      for Group 2. Another nine cases, implanted with arterial catheter and reservoir
      did not qualify for HAI due to subsequent extra-hepatic spread of the disease
      (Group 3). For the rest of the patients (Group 4, n = 28), HAI could not be
      applied, due to existing extrahepatic spread of gastric cancer, which exhausted
      these patients. The 50% survival was 104 days and 93 days for Group 3 and Group
      4, respectively. HAI therapy showed considerably improved survival for gastric
      liver metastasis. However, its indication needs to be clarified further.

PMID- 7574748
TI  - [A comparison of intra-arterial chemoembolization and infusion chemotherapy for
      liver metastases of breast cancer].
AB  - Seventeen patients with liver metastases of breast cancer were treated with a
      combination of intra-arterial chemotherapy and endocrine therapy at our hospital
      from 1986 to 1994. Of 17 patients, 9 were treated with transarterial
      chemoembolization through hepatic artery using 40-50 mg/body of 4'epi-adriamycin
      (epi-ADM) and lipiodol, and the other 8 were treated with hepatic infusion
      chemotherapy using 20-30 mg/body of epi-ADM every 2 weeks. All patients were
      followed by endocrine therapy with oral administration of 800-1,200 mg/day of
      medroxyprogesterone acetate (MPA). The results were as follows: 1) The comparison
      of response rate between the two groups was not substantially changed (44.4% x
      4/9 in TAE group and 50.0% x 4/8 in Reservoir group). 2) Duration of response was
      4-45 months (mean 25 months) in TAE group and 3-15+ alpha months (mean 8.7
      months) in Reservoir group. But in the latter group, 3 patients are now under
      treatment. 3) At one year, the survival rates were 44.4 percent in TAE group and
      50.0 percent in Reservoir group. We conclude that combination of intra-arterial
      chemotherapy and endocrine therapy is a useful treatment modality for controlling
      liver metastases of breast cancer.

PMID- 7574749
TI  - [Evaluation of intraoperative peritoneal cytology and intraperitoneal
      chemotherapy using CDDP combined with MMC for gastric carcinomatous peritonitis].
AB  - A cytological examination in the lavaged peritoneal fluid during operation was
      performed in 462 patients with gastric cancer. The incidence of positive cytology
      was 36% in serosal invasion cases. The prognosis of positive cytology cases
      without peritoneal dissemination was slightly better than the P (+) cases. The
      incidence of the positive cytology was 48% in patients with serosal invasion more
      than 16 cm2. The prognosis of patients with serosal invasion below 32 cm2 was
      significantly better than in the patients with above 32 cm2. Intraperitoneal
      repeated administration of MMC 10 mg/body and CDDP 40-50 mg/body was continued
      one a month via the drug delivery system. Negative change of cytology was
      observed in 7 out of 14 patients, and the prognosis of these patients was better
      than that of the unchanged cytology group. Side effects such as severe
      gastrointestinal symptoms and bone marrow toxicities were not observed. Further
      studies should be done to confirm the efficacy of the intraperitoneal
      chemotherapy in terms of the prolongation of life.

PMID- 7574750
TI  - [Therapy of carcinomatous peritonitis by the angiogenesis inhibitor TNP-470 in
      mice: analysis of timing and doses for intraperitoneal administration].
AB  - In order to perform therapy for carcinomatous peritonitis by a new angiogenesis
      inhibitor, TNP-470, we investigated the effective timing and the optimal doses
      for intraperitoneal administration using two mice models. In both carcinomatous
      peritonitis models caused by M 5076 tumor and B 16 melanoma, the early
      administration of TNP-470 within one week after tumor inoculation extended the
      survival times of the mice receiving the drugs, whereas the administration of TNP
      470 one week or later after inoculation did not affect the survival time.
      However, there were significant differences in the effective therapeutic doses of
      TNP-470 between the two models. It is important to select the best timing and
      doses for intraperitoneal administration of TNP-470 based on the state of
      angiogenesis and the sensitivity of the tumor tissues to TNP-470.

PMID- 7574751
TI  - [Experimental and clinical study on intraoperative local infusion chemotherapy
      (ILIC) for advanced gastric carcinoma].
AB  - An intensive chemotherapy combined with surgery, termed "intraoperative local
      infusion chemotherapy (ILIC)", was devised. The ILIC procedure is to infuse 50 mg
      of cisplatin through the feeding artery to the tumor, which has been isolated
      from blood flow by clamping the stomach and blood vessels, before radical
      surgery. An experiment in dogs showed considerable free Pt transfer into thoracic
      lymph after ILIC. Sum total Pt in the thoracic lymph after ILIC (294.5
      micrograms/3 h) was 4.3 times that after IV administration (68.3 micrograms/3 h).
      In ILIC, AUC of free Pt in the thoracic lymph was about 5.8 times that in
      peripheral blood. ILIC was applied in 24 advanced gastric cancer patients,
      consisting of 6, 2, 4 and 12 in pTNM stage II, IIIA, IIIB and IV, respectively.
      Pt concentration of the tissues was high in the tumor (23.22 micrograms/g) and
      the regional lymph nodes (2.95 micrograms/g) compared to that in the serum (0.45
      microgram/ml). The survival rate (Kaplan-Meier) in the ILIC patients was
      significantly higher than that of control patients (matched pair method) from
      among patients treated by surgery alone. No fatal complications were encountered
      in any patient treated by ILIC.

PMID- 7574752
TI  - [Pharmacokinetic study of intraperitoneal cisplatin chemotherapy for gastric
      cancer as an adjuvant setting].
AB  - The pharmacokinetic studies of intraperitoneal cisplatin (CDDP) for gastric
      cancer were discussed elsewhere, but those studies were investigated in patients
      with ascites. The purpose of this study is to compare the difference in
      pharmacokinetics between patients with malignant ascites and those curatively
      resected without ascites. One hundred mg of CDDP and 300 ml of saline were
      administered intraperitoneally for 9 curatively resected patients by catheter
      just after operation, and the same doses of CDDP were administered for 3 advanced
      or recurrent patients with ascites just after removal of whole fluid. Blood
      samples were corrected at 6 points after administration. Results were as follows:
      The 0-t area under the curve (AUC) and the Cmax of both total and free CDDP in
      the patients without ascites was higher than in the patients with ascites. The 0
      infinity AUC and MRT of the ascites patients were higher than in the patients
      without ascites. These data suggest that intraperitoneal CDDP chemotherapy for
      gastric cancer as an adjuvant setting is more effective than chemotherapy for
      advanced malignant ascites patients.

PMID- 7574753
TI  - [Preoperative neoadjuvant chemotherapy with a combination of 5-fluorouracil,
      adriamycin and cisplatin (FAP) for advanced esophageal cancer invading trachea or
      main bronchus].
AB  - Conventional irradiation and systemic chemotherapy is scarcely effective for
      advanced esophageal cancer invading trachea or main bronchus. Therefore, to
      reduce the area of invasion and suppress distant metastasis, we have
      preoperatively treated 4 patients suffering from advanced esophageal cancer
      invading the trachea or main bronchus by neoadjuvant chemotherapy (FAP) as
      follows: 2 times every 4 weeks, CDDP 100 mg and ADR 50 mg on day 1 and continuous
      infusion of 5-FU 1,000 mg/day for 7 days. The response rate (PR) was 75% (3/4).
      In 2 of 4 patients (50%), no cancer cells except broad fibrosis were detected
      histologically in the region of the trachea or main bronchus suspected to be
      invaded. There was no severe complication. This FAP regimen is suspected to be
      useful chemotherapy for advanced esophageal cancer.

PMID- 7574754
TI  - [Preoperative intra-arterial chemotherapy with THP-ADR for locally advanced
      breast cancer].
AB  - We treated 8 patients of Stage III and IV breast cancer preoperatively with THP
      ADR intra-arterial infusion chemotherapy. The median dose was 200 mg with a range
      from 150 to 310 mg. The response rate of THP was 75.0% compared to 66.7% of ADR.
      Leucopenia was observed during THP treatment with a lower frequency of alopecia.

PMID- 7574755
TI  - [Neoadjuvant intraarterial chemotherapy with dose intensification in locally
      advanced breast cancer].
AB  - Sixteen patients with advanced breast cancer were treated with neoadjuvant
      intraarterial chemotherapy with high dose epirubicin. The following results were
      obtained: 1) Excellent down-staging effects were confirmed. Response rate of the
      primary tumor was 81.3%. 2) Leukopenia was the dose-limiting factor, and 81.3% of
      patients had WHO grade 2 or more leucopenia. However, the regimen was completed
      with supportive therapies. 3) At a median follow-up of 17 months, improved
      survival rates were noted. The present study showed the efficacy of neoadjuvant
      intraarterial chemotherapy with high dose epirubicin in the treatment of locally
      advanced breast cancer.

PMID- 7574756
TI  - [Therapeutic effectiveness of hyperthermia and relation to glutathione
      concentration in the tumor tissues].

PMID- 7574757
TI  - [Clinico-pathological studies on three preoperative combined treatments for
      rectal cancer].
AB  - To prevent postoperative local recurrence of rectal cancer, we treated patients
      using preoperative hyperthermia (5-6 times), irradiation (total 30 Gy) and 5
      fluorouracil suppository (2,000-2,500 mg). The subjects were 31 patients given
      combined treatments and 28 patients given surgery alone. The results were as
      follows: 1. Histologically, therapeutic effects were recognized in 80.6% of
      patients receiving combined treatments. 2. The mean distance from the adventitia
      to the site of cancer infiltration was 6.54 mm in the combined treatments group
      and 3.35 mm in the surgery alone group. The difference between the two was
      significant (p < 0.05). 3. The rate of local recurrence in the combined
      treatments group was less than that in the surgery alone group. 4. No systemic
      side effects nor severe complications were observed during hospitalization in the
      combined treatments group. 5. The survival rate of the combined treatments group
      was higher than that of the surgery alone group. It was considered that combined
      preoperative treatments for rectal cancer were beneficial to survival and local
      control.

PMID- 7574758
TI  - [Assessment of serial carcinoembryonic antigen (CEA): monitor to evaluate
      efficacy of continuous intrahepatic chemotherapy for nonresectable liver
      metastases of colorectal carcinomas].
AB  - It is not easy to evaluate the efficacy of the regional chemotherapy for liver
      metastases early by imaging procedures. We attempted to find out whether the
      changes of serial CEA levels under treatment were useful to predict the
      therapeutic progress for 24 patients with nonresectable liver metastases of
      colorectal cancer, but without extrahepatic tumor. Continuous intrahepatic
      chemotherapy was performed in all cases with 5-FU (250 mg/body) over 7 days,
      followed by a 7-day therapy-free interval for a mean 4.5 months. CT examination
      revealed CR or PR in 20 patients, mean 4 months after the beginning of treatment,
      and PD in 4. Among the CR or PR patients, serial CEA levels at 1 month after the
      beginning of chemotherapy were decreased in most cases, and not changed or little
      increased in a few cases; but at 2 months after, decreased markedly in all cases.
      On the other hand, those in PD they were group increased markedly about three
      times as much as pretreatment. At the same time, Al-p and LDH values were normal
      in the regression group, but abnormal in the progression group. The changes in
      serial CEA levels at 1 months after chemotherapy were useful to predict the
      therapeutic progress. Especially in the CEA-increased patients at 1 month after
      treatment, the Al-p and LDH values were helpful for evaluation.

PMID- 7574759
TI  - [Pharmacokinetic comparison of intraarterial and intraportal infusion of
      adriamycin in regional chemotherapy of the liver].
AB  - We investigated the adriamycin (ADR) pharmacokinetics following intraarterial and
      intraportal infusion under hepatic venous isolation and charcoal hemoperfusion
      (HVI.CHP). HVI.CHP was used to measure the first-pass amount of adriamycin
      through the liver and to reduce hepatic re-entry of the drug. Beagles underwent a
      10-min ADR infusion (1 mg/kg) either through the hepatic artery (group I, n = 5)
      or the portal vein (group II, n = 5) under a 20-min HVI.CHP. During HVI.CHP, the
      hepatic venous flow rate and plasma ADR levels in prefilter (hepatic venous
      level), postfilter and peripheral blood were serially measured. Based on these
      measurements, the hepatic extraction ratio (HER) of ADR was calculated. Areas
      under the time-concentration curves of prefilter levels in groups I and II were
      6.1 +/- 1.6 and 16.9 +/- 5.0 micrograms.min/ml, respectively, showing a
      significant difference between two groups (p < 0.01). On the contrary, HER of
      group I (81.2%) was significantly higher than that of group II (47.2%, p < 0.01).
      These results indicate that intraarterial infusion of ADR is superior to
      intraportal infusion in terms of local drug delivery to the liver and systemic
      drug toxicities.

PMID- 7574760
TI  - [Pharmacokinetic evaluation of complete infrarenal inferior vena caval isolation
      and charcoal hemoperfusion for intra-arterial chemotherapy of pelvic tumors].
AB  - Regional chemotherapy for malignant pelvic tumors is disappointing due to the
      poor tumor response and dose-limiting systemic toxicity. This study was designed
      to determine whether a novel venous isolation-charcoal hemoperfusion system could
      limit systemic exposure to chemotherapeutic agents after regional arterial
      infusion. Adriamycin (2 mg/kg) was continuously administered in the internal
      iliac arteries of beagles under complete isolation of the infrarenal inferior
      vena cava and extracorporeal charcoal hemoperfusion (IVCI.CHP). Control beagles
      received adriamycin at the same dosage without IVCI.CHP. Plasma adriamycin
      concentrations were measured in the left carotid artery (systemic level) at
      intervals of up to 40 minutes after the start of drug infusion. In animals with
      IVCI.CHP, the drug levels were also determined at the inlet and outlet of a CHP
      filter. The mean drug extraction ratios by the CHP filter averaged 88%. As a
      result, animals with IVCI.CHP showed a significant reduction in systemic drug
      levels at all measuring time points compared to controls. The peak systemic
      levels of adriamycin were 0.8 +/- 0.1 and 2.3 +/- 0.8 micrograms/ml,
      respectively, in IVCI.CHP and control animals (p < 0.01). IVCI.CHP accomplished a
      significant reduction in systemic exposure to adriamycin after iliac arterial
      infusion. This novel system will allow regional delivery of high-dose cytotoxic
      agents with little systemic toxicity for pelvic tumors.

PMID- 7574761
TI  - [The study of chemotherapy via the reservoir to colo-rectal cancer patients with
      liver metastases].
AB  - From January 1986 to December 1994, we administered intra-arterial chemotherapy
      via the reservoir to 26 colo-rectal cancer patients with liver metastases. The
      protocol of this chemotherapy was administration of ADM 30 mg/body/4 wks, MMC 10
      mg/body/2 wks and 5-FU 500 mg/body/2 wks. Responses to this chemotherapy were PR
      in 8 cases, NC 3 cases, PD 14 cases and unknown 1 case. The rate of response was
      32.0%. Side effects were shown in 12 cases (46.2%), and trouble with the
      reservoir in 5 cases (20.8%). Survival times of patients were from 5 months to 42
      months (average 13.6). We think that this intra-arterial chemotherapy via the
      reservoir was effective for patients with liver metastases from colo-rectal
      cancer.

PMID- 7574762
TI  - [Experience in intra-hepatic-arterial chemotherapy and hepatic resection for
      metastatic colorectal cancer].
AB  - Out of 213 consecutive cases of colorectal cancer patients, 39 patients had liver
      metastasis (31 synchronous metastases and 8 metachronous metastases). One-and 3
      year survivals of these patients with liver metastases were 46.5% and 30.1%,
      respectively. Twenty-four patients who were treated with intra-hepatic-arterial
      chemotherapy had better survival rates of 54.7% at 1 year, and 36.5% at 3 years
      than non-treated patients. Fifteen patients who underwent curative hepatic
      resection had better survival rates of 83.1% at 1 year, and 48.5% at 3 years than
      non-resected patients. Thirteen patients who underwent curative hepatic resection
      followed by intra-hepatic-arterial chemotherapy had good survival rates of 80.8%
      at 1 year, and 53.9% at 3 years. Seven patients who had multiple metastases to
      both lobes, were treated with intra-hepatic-arterial chemotherapy. These patients
      had a better survival rate of 22.9% at 1 year than non-treated patients.

PMID- 7574763
TI  - [Outcomes of effective treatment of cases of metastatic liver tumors by intra
      arterial infusion chemotherapy].
AB  - We studied the prognoses of unresectable liver tumors, including 31 colorectal
      cancers and 10 gastric cancers treated by intra-arterial infusion chemotherapy
      using an implantable reservoir. Adriamycin, epirubicin, or cisplatin were
      administered intermittently early on. Cisplatin and 5-FU combined therapy were
      given later. In nine with colorectal metastases and six with gastric metastases,
      metastatic lesions decreased, and in 4 patients with metastatic lesions could be
      resected. But in many patients, hepatic and other organ recurrences were
      observed. We need to try many other treatments.

PMID- 7574764
TI  - [Intra-arterial infusion chemotherapy for advanced liver metastases from lung
      cancer via implantable vascular access: report of six cases].
AB  - Six patients with advanced liver metastases judged as a survival limiting factor
      from lung cancer were treated with intra-arterial infusion chemotherapy employing
      totally implantable vascular access. The treatment regimen included 5
      FU/CDDP/EPIR/MMC/etoposide in various combinations and this therapy was repeated
      as long as possible. There were no serious side-effects or complications, such as
      bone marrow suppression or gastrointestinal symptoms. The therapy could be
      continued for a mean duration of 7.2 months (ranging from 2 to 13 months). Cause
      of death was due to extra-hepatic lesion in all 5 patients. The direct effect on
      liver metastases reviewed on CT scan was 83.3% (CR: 1, PR: 4, NC: 1), and the
      median survival period was 108 days (for small-cell group: 92 days; for non-small
      cell group: 407 days). We conclude that this therapy is useful in the treatment
      of liver metastases from lung cancer because of its limited toxicity and high
      direct effect.

PMID- 7574765
TI  - [A study of chemotherapy for patients with severely advanced gastric cancer-
      comparison of chemotherapy and route].
AB  - We analyzed the clinical response, toxicities, ambulatory and overall survival
      time among 51 patients with inoperable gastric cancer, to evaluate chemotherapies
      and drug delivery routes. Twenty-nine patients were treated by Methotrexate/5-FU
      (FMTX) therapy and 22 by 5-FU/CDDP (FP) therapy. Twenty-five patients were
      treated by intra-arterial (IA) route and 26 by intra-venous (IV). The response
      rate of IA therapy was higher than that of IV therapy (p < 0.05), 48% and 19%,
      respectively. Median survival times of FMTX and FP were 361 and 289 days,
      respectively, and the 1-year survival rates of FMTX and FP were 44% and 33%,
      respectively, with no significant differences. Duration of home chemotherapy with
      FMTX was longer than that with FP, at 130 and 85 days, respectively. There was no
      difference between duration of home chemotherapy of IA and that of IV. IA
      chemotherapy showed a higher response rate than IV, but there were no differences
      in the incidence of side effects and ambulatory and overall survival time.

PMID- 7574766
TI  - [Efficacy of repeated hepatic dearterialization combined with intra-arterial
      infusion chemotherapy for unresectable tumors of the liver].
AB  - In the present study, repeated hepatic dearterialization combined with intra
      arterial infusion chemotherapy was performed in patients with unresectable tumors
      of the liver. Of 36 patients, 16 had primary liver tumors (13 hepatocellular
      carcinomas and 3 cholangiocellular carcinomas), while 20 had metastatic tumors (7
      gastric carcinomas, 10 colon carcinomas, 2 pancreatic carcinomas, and 1 gastric
      carcinoid). A significantly better survival outcome was found in those with intra
      arterial infusion chemotherapy and those without cirrhosis. In the HCC cases,
      those with the therapy tended to show a better survival as compared with the
      natural history. Remarkable tumor regression was found in four (67%) of six
      patients with metastases of gastric cancer.

PMID- 7574767
TI  - [The efficacy of transarterial immuno-embolization therapy in patients with
      unresectable hepatocellular carcinoma].
AB  - We devised a new therapeutic modality for multiple hepatocellular carcinoma (HCC)
      consisting of transarterial immuno-embolization (TIE) using OK-432 and
      fibrinogen, and applied the treatment to 22 patients with advanced HCC who had
      been insensitive to TAE, and 21 patients who had no treatment. Nineteen patients
      had a high AFP level of more than 200 ng/ml. The serum AFP level decreased in 15
      patients after TIE, and in 7 patients the AFP level decreased to less than 30%.
      Furthermore, a marked reduction in tumor size was observed in 69% after TIE. We
      report 61% 1-year, and 3-year survival rate for cases who had been insensitive to
      TAE, and 86% 2-year survival rate for those who selected TIE as the first choice.
      A high fever of more than 38 degrees C occurred in all cases, and hypotension
      less than 80 mmHg was observed in 42% patients. No deterioration of liver
      function and no disturbance of the coagulation-fibrinolysis system due to TIE
      except in one patient with liver failure after TIE.

PMID- 7574768
TI  - [Clinical effects and immunological analysis of intraabdominal and intrapleural
      injection of lentinan for malignant ascites and pleural effusion of gastric
      carcinoma].
AB  - Twenty-one patients with malignant peritoneal or pleural effusions of gastric
      carcinomas were treated with intracavitary injection of lentinan (LNT). LNT was
      injected at a dosage of 4 mg/week for 4 weeks. In total, fifteen (71%) of twenty
      one patients demonstrated clinical responses. Toxicity caused a high fever in
      only one case. LAK and ATK activities induced from peritoneal exudate cells (PEC)
      after culture with autologous tumor and interleukin-2 were examined before and
      after LNT injection. ATK activity was augmented, but LAK activity was reduced
      after LNT injection. These results indicate that intracavitary injection of LNT
      is a useful treatment for malignant effusions, and that LNT augments the
      induction of cytotoxic T-lymphocytes.

PMID- 7574769
TI  - [Antitumor effects of liposome-entrapped carboplatin (Lipo-CBDCA) after
      intraperitoneal administration in rats bearing carcinomatous peritonitis].
AB  - We examined the distribution of Lipo-CBDCA after intraperitoneal administration
      and antitumor effects in rats. The serum levels of platinum in Lipo-CBDCA were
      lower than in free-CBDCA intraperitoneal or intravenous administration at 15 and
      30 min. after administration. After 3 hours, Lipo-CBDCA showed higher levels of
      serum platinum than free-CBDCA. These data showed the slow release of Lipo-CBDCA.
      The antitumor effects of Lipo-CBDCA were studied in rats with peritoneal
      dissemination due to AH 130 tumors. Intraperitoneal treatment with Lipo-CBDCA
      prolonged the life span significantly compared with Lipo-CBDCA. No side effects
      of chemotherapy were found in the liver, kidney, spleen or small intestine. A
      gastric cancer patient suffering from carcinomatous peritonitis with remarkable
      ascites was treated with Lipo-CBDCA intraperitoneally. After several injections
      of Lipo-CBDCA, the ascites disappeared completely and the CEA level of ascites
      decreased dramatically. These results indicate that intraperitoneal chemotherapy
      with Lipo-CBDCA may be more effective than free-CBDCA to manage carcinomatous
      peritonitis, and may be therapeutically useful without toxic side effects.

PMID- 7574770
TI  - [Intraperitoneal distribution of drug after gastric surgery].
AB  - To evaluate intraperitoneal distribution of drug after surgery, a radiographic
      study using peritoneography was performed. Five cases with positive
      intraoperative cytology of gastric carcinoma were studied. The tip of the
      subcutaneous injection catheter was located in the Douglas's fossa
      intraoperatively. As control group, 7 cases of inguinal hernia who underwent
      radical resection for gastrointestinal carcinoma and 2 cases who failed
      intraperitoneal chemotherapy through injection port, underwent peritoneography.
      The distribution of contrast medium in the peritoneal cavity was compared between
      groups. (Conclusion) The distribution of drug after gastric surgery was observed
      in all of the peritoneal cavity below the transverse colon. Distribution was not
      observed in the region where lymphadenectomy or bursectomy was done. The
      peritoneum has an important role in the distribution of drugs in the peritoneal
      cavity.

PMID- 7574771
TI  - [Prognostic evaluation of peritoneal lavage smears and gastric wall brushing
      smears in gastric cancer surgery].
AB  - We investigated the correlation of intraoperative peritoneal lavage smear and
      gastric wall brushing smear cytology with macroscopic and histologic findings and
      prognosis, in 216 patients with gastric cancer. Some 196 of these patients
      underwent gastric resection and 20 did not. The incidence of positive cancer
      cells determined by these methods was significantly correlated with gastric
      resection, tumor invasion, and peritoneal dissemination. Among patients without
      macroscopic peritoneal dissemination, four were found to have positive peritoneal
      lavage smears or gastric wall brushing smears, respectively. The prognosis of
      these patients did not differ from that of patients with metastases to the
      adjacent peritoneum but not the distant peritoneum. These results suggest that
      peritoneal lavage smears and gastric wall brushing smears are useful for
      predicting the peritoneal cancer dissemination. Therefore we intend to target
      patients with no peritoneal metastases (Po) showing positive peritoneal cytology
      for intensive treatment.

PMID- 7574772
TI  - [Chemohyperthermic peritoneal perfusion and subtotal peritonectomy for
      peritonitis carcinomatosa in gastroenteric cancer].
AB  - A new operative procedure, called subtotal peritonectomy (SP), in combination
      with chemohyperthermic peritoneal perfusion, was developed for the treatment of
      peritonitis carcinomatosa in gastrointestinal cancer. SP includes resection of
      primary lesion, colon, small bowel, spleen, and gall bladder and parietal
      peritonectomy. Six patients with gastric cancer and two patients with colon
      cancer underwent these procedures. A great deal of discharge from the peritoneal
      cavity, an increase in systemic vascular resistance index, and a decrease in
      central venous pressure represented much decrease in circulatory volume on days 1
      to 2 postoperatively. This state improved at 3 to 4 days after operation.
      Histopathological study revealed multiple peritoneal seedings with negative
      surgical margins in all patients. There were no related deaths though bleeding,
      perforation, and abscess occurred in two patients each. One patient died of
      peritoneal recurrence after one year, but the other have survived.

PMID- 7574773
TI  - [Pharmacological and biochemical investigation of intracavital fluorinated
      pyrimidine chemotherapy].
AB  - We investigated the biochemical and molecular pharmacological parameters of
      fluorinated pyrimidines using malignant cells in pleural effusion or ascites from
      patients with malignant disease both before and after fluorinated pyrimidine
      chemotherapy, either systemically or intravesically. In four out of fifteen
      cancer patients, we could analyze the alteration of thymidylate synthase (TS)
      catalytic activity both before and after the treatment, showing that there was a
      decrease ranging 28% through 96.9%. We also analyzed a level of TS messenger RNA
      and TS protein using molecular biotechniques. None of these mutual correlations
      has so far been demonstrated, indicating that the data were analyzed through
      samples from patients not responding to the fluorinated pyrimidines. In a
      responding patient with advanced breast cancer, pre-treatment total TS protein
      was 130 fmol/mg and the TS activity was 3.27 pmol/mg/min. After intrapleural
      instillation of a combination of 5-FU 250 mg and leucovorin 3 mg, the total
      amount and the catalytic activity of TS could be measured. On the 11th day of
      treatment, the TS protein level decreased to 26 fmol/mg and the TS catalytic
      activity also decreased to 0.1 pmol/mg/min resulting in a TS inhibition rate of
      92.3 percent. On the 17th day, the patient's malignant pleural effusion
      disappeared almost completely, suggesting that substantial TS inhibition may
      reflect the clinical evidence. This particular data showed that it would be
      predictable for clinical outcome to evaluate these parameters before and after
      fluorinated pyrimidine chemotherapy. Further study is warranted to evaluate the
      exact role of analyzing these parameters in clinical practice.

PMID- 7574774
TI  - [Relationship between intraoperative pleural lavage cytology and recurrence in
      pleural cavity after resection of lung metastasis from colorectal cancer].
AB  - Seventeen patients with lung metastases from colorectal cancer underwent
      intraoperative pleural lavage cytology immediately after thoracotomy from August
      1988 to December 1994. Patients with pleural effusion and/or dissemination were
      excluded. The median followup period was 34 months (range 3-52 months). Of the 17
      patients, 13 were cytologically negative (76%, group A) and 4 were positive (24%
      group B). Recurrence rate in the pleural cavity was 25% (1/4) in group B and 0%
      (0/13) in group A. The three-year survival rate was 0% in group B and 78% in
      group A, respectively. These results indicate that intraoperative pleural lavage
      cytology is useful in the assessment of prognosis, and locoregional therapy
      should be considered for cytology positive group.

PMID- 7574775
TI  - [Intraperitoneal infusion therapy of MTX and 5-FU for advanced gastric cancer and
      its peritoneal metastasis].
AB  - We administered methotrexate (MTX) and 5-fluorouracil (5-FU) into the peritoneal
      cavity as chemotherapy after operation for advanced gastric cancer from a port
      implanted subcutaneously during the operation, every or every other week. It has
      been said that MTX tends to be kept in the peritoneal cavity, so the kinetics of
      MTX is important when it was administered there in. We investigated the
      concentrations of MTX in the peritoneal cavity and serum with infusion into the
      peritoneal cavity (IP), and compared it with intraarterial (IA) and intravenous
      (IV) administration. The results were the lower serum concentration of MTX in IP
      than in both IA and IV at 1-2 hours after infusion, but thereafter it was the
      same level in each group. The intraperitoneal concentration of MTX was lower than
      the detectable level at 24-48 hours after infusion. On the other hand, we
      investigated the side effects of this therapy, and only one of 20 cases given
      therapy many times had nausea and vomiting. So the intraperitoneal infusion
      therapy of MTX and 5-FU seemed to be safe.

PMID- 7574776
TI  - [T cell receptor V beta repertoire of locoregional lymphocytes in malignant
      effusions].
AB  - We analyzed the T cell receptor (TCR) V beta repertoire of lymphocytes obtained
      from patients with malignant effusion treated by locoregional immunotherapy.
      Polymerase chain reaction using a panel of V beta subfamily specific
      oligonucleotide primers(V beta 1-20) was employed after reverse transcription of
      mRNA isolated from the locoregional cells. No major oligoclonality of TCR
      repertoire was observed in effusion lymphocytes before the treatment. The
      expression level of V beta 13.1 repertoire was significantly higher in effusion
      lymphocytes than in peripheral blood lymphocytes before treatment. V beta 20 gene
      expression increased significantly after locoregional administration of OK-432.
      It is suggested that TCR V beta 13.1 may be responsible for effusion lymphocytes
      and TCR V beta 20 for OK-432-related antigenic stimulus.

PMID- 7574777
TI  - [Antitumor effect of intratumoral administration of BRM: inhibition of tumor cell
      invasion in vitro].
AB  - The effect of intratumoral administration of BRMs in Meth-A solid tumor has been
      analyzed in BALB/c mice. The effect of BRMs on in vitro invasion by murine RL
      male-1 leukemia cells was studied using Biocoat Matrigel Invasion Chamber (Becton
      Dickinson Labware). We determined the ability of tumor cells to penetrate
      matrigel-coated filters in the presence or absence of BRM. PSK or OK-432
      inhibited tumor cell invasion of matrigel-coated filters in a dose-dependent
      manner. PSK, OK-432 and Cepharanthin inhibited invasion of murine Colon 26
      carcinoma cells and human A 375. S2 melanoma cells. On the other hand,
      polysaccharide preparations without protein, Lentinan or Sonifilan inhibited
      neither tumor growth nor tumor cell invasion.

PMID- 7574778
TI  - [Antitumor effect of MMC mixed in Beriplast P].
AB  - We attempted to mix an anticancer drug. MMC, with a fibrinogen preparation,
      Beriplast P (B. P.). First, we examined how MMC was gradually released from its
      mixture. As the result, its release depended on the MMC concentration in B. P.,
      and the release rate of 1.0 mg MMC from 100 microliters B. P. was 1.6 mg/30 min.
      Second, we examined the safety of the conjugated drug for normal tissue, because
      MMC is one of anticancer drugs causing serious damage to normal tissue. When the
      conjugation of 100 microliters B. P. and below 1.6 mg MMC was coated within one
      square centimeter, the drug was safe for the endothelium of artery and vein, and
      the intestinal wall. Third, we attempted an experiment on both the antitumor
      effect and the role of survival prolongation of the conjugated drug in a mouse
      carrying a malignant tumor. MMC conjugated with Beriplast P had a highly
      antitumor effect, which caused necrosis in the cancer cells in unstable
      conditions. Also, its conjugation drug could inhibit the growth of cancer cells
      in stable conditions, and prolonged the survival period. From these results, the
      mixture of MMC and B. P. was found to possess an MMC releasing effect, was safe
      for normal tissues, and showed high antitumor effect with prolongation of the
      survival period.

PMID- 7574779
TI  - [Endoscopic injection of methotrexate bound to activated carbon particles in the
      treatment of gastric cancer].
AB  - A new dosage formulation (MTX-CH), composed of fine activated carbon particles
      absorbing methotrexate (MTX), distributes concentrated MTX for long periods of
      time to the regional lymph nodes as well as to the injection site, in animal
      experiments. MTX-CH would enhance the therapeutic effects not only on the primary
      lesion but also on the lymphatic metastasis. As clinical trials, (A) in five
      patients with early gastric cancer, MTX-CH at 50 to 200 mg/person of MTX was
      injected endoscopically in and around the primary lesion before operation.
      Surgically removed specimens showed that three out of the 5 primary lesions had
      disappeared or were necrotic, and the remaining two lesions had shrunk. (B) Three
      patients with contraindication to surgery received the endoscopic injection of
      MTX-CH. The MTX-CH injected at 250 to 1,500 mg/person into and around the primary
      lesion of relatively early gastric cancer resulted in the complete disappearance
      of the primary lesions for 14 to 24 months up to the present time without
      enlargement of the lymph nodes. It was thought that local injection of MTX-CH
      will be effective therapy, especially for gastric cancer with potential lymphatic
      metastasis in patients with contraindications to surgery.

PMID- 7574780
TI  - [Trial of a treatment for lymph node metastases in patients with breast cancer
      using aclarubicin bound to activated carbon particles].
AB  - A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine
      activated carbon particles, was developed for the treatment of lymph node
      metastases in patients with breast cancer. In a mice experimental model, ACR-CH
      had superior therapeutic effects on lymph node metastases compared to the same
      dose of ACR aqueous solution. In clinical trials, patients with breast cancer
      received a local injection of 10 mg/person of ACR in the form of ACR-CH or ACR
      aqueous solution just before mastectomy. In the regional lymph nodes removed by
      the operation, the ACR concentration of 40.7 micrograms/g in patients given ACR
      CH was higher than the 25.1 micrograms/g in patients given ACR aqueous solution,
      whereas in blood plasma the concentration was higher in patients given ACR
      aqueous solution than in those given ACR-CH.

PMID- 7574781
TI  - [Development of 5-fluorouracil incorporated in microspheres for peritoneal
      carcinomatosis--animal experiments].
AB  - A new dosage formulation (5-FU-MS), composed of 5-fluorouracil (5-FU)
      incorporated in polyglactin microspheres, was studied by animal experiments,
      which revealed the following results. Intraperitoneal 5-FU-MS delivered greater
      concentrations of 5-FU for longer periods selectively to the intraperitoneal
      tissues, whereas it delivered a lower concentration to the blood plasma, than 5
      FU solution did in rats. In mice, the 50% lethal dose value of intraperitoneal 5
      FU-MS was 535 mg/kg. The toxicity of 5-FU-MS was less than 1/2 that of
      intraperitoneal 5-FU solution, of which the 50% lethal dose value was 242 mg/kg.
      Intraperitoneal 5-FU-MS at 200 mg of 5-FU/kg improved the survival curve of mice
      with peritoneal carcinomatosis better than the identical dose of 5-FU solution.

PMID- 7574782
TI  - [Experimental study on cisplatin microspheres incorporated in polylactic acid and
      polyethylene glycol acid].
AB  - Cisplatin incorporated into polylactic acid/polyethylene glycol acid blend
      polymeric microspheres was prepared as a dosage (CDDP-MS) by the solvent
      evaporation method in an oil-in-oil emulsion system. When CDDP-MS was preserved
      in phosphate-buffer saline, the dissolution rate of cisplatin from CDDP-MS was
      14% after one day, 25% after 5 days, 33% after 7 days, 66% after 21 days and 85%
      after 30 days. CDDP-MS and CDDP aqueous solution (CDDP-SOL) were
      intraperitoneally administered to compare the tissue distribution of cisplatin in
      42 rats each. On days 0.5, 1, 5, 7, 14 and 21, omentum, lung, liver and kidney
      were removed, and the CDDP concentration was measured. The CDDP concentration of
      the CDDP-MS group was maintained at a high level in the omentum for a long time.
      On the other hand, the CDDP level of CDDP-MS group was low in the lung, liver and
      kidney, compared with the CDDP-SOL group. Consequently, it was suggested that
      CDDP-MS is useful as a carrier in a drug delivery system, since it improves the
      burst effect and releases CDDP for a long time without serious side effects.

PMID- 7574783
TI  - [Immunopotentiation by OK-432 ointment to apply to the mouse abdominal skin].
AB  - The immunopotentiating effect of a streptococcal preparation, OK-432 (Picibanil),
      mixed with an ointment based Lanolin, was examined. The mixture was applied to
      mouse abdomen. The effect of OK-432 ointment was compared with those of OK-432 ip
      and sc. The leucocyte count in the abdominal cavity increased in 3.6 x 10(6) and
      12.5 x 10(6) on the 3rd day after ointment application and ip injection of 5 KE
      OK-432, respectively. The result indicated that OK-432-Lanolin applied to the
      abdominal skin wall affected the abdominal cavity. IL-6 and IFN-gamma in the
      abdominal cavity increased in 1.4 ng and 9 ng, respectively, after applying 5 KE
      OK-432 ointment. From these results the treatment with OK-432 ointment on the
      abdominal skin exhibited an immunomodulatory effect on the abdominal cavity.

PMID- 7574784
TI  - [Treatment of solid tumor by a small amount of direct current].
AB  - Solid tumor treatment was given in our animal laboratory to determine the
      mechanism of tumor disappearance by direct electric current, and clinical trials
      were done on 9 far advanced recurrent rectal cancers. Solid tumors of Yoshida
      sarcoma in Donryu rat were treated by 1 mA of constant direct current for 1 hour
      a day, for 4 days. The tumors disappeared in 13/16 within 21 days. Positive
      results of DNA Nick-end labeling and ladder patterns in the gel electrophoresis
      of DNA were observed in the regressing tumor specimen. It is considered that
      apoptosis is the one of the mechanisms of a disappearing tumor. As for the
      clinical trial concern, in 9 cases of rectal cancer, one CR and 5 PR were seen.

PMID- 7574785
TI  - [Chemoradiation therapy with low-dose carboplatin for squamous cell carcinoma of
      the esophagus].
AB  - Twenty-three patients with squamous cell carcinoma of the esophagus were treated
      with low-dose carboplatin and radiation therapy. Patients received 1.6 Gy
      fractions daily; the total dose was 50-70 Gy for 14 unresectable cases, and 30-40
      Gy for 8 resectable cases as preoperative irradiation. Carboplatin (30 mg/m2/day)
      was administered intravenously just before the irradiation; total dose was 1,100
      2,000 mg for the unresectable cases, and 750-1,200 mg for the resectable cases.
      The response rate of the unresectable tumors was 86% (CR 5, PR 7, and NC 2).
      Three of the five CR patients were alive without recurrence for more than 2
      years. The response rate of the resectable tumors was 75%. Although major
      toxicity was bone marrow suppression, there were no serious complications. These
      results suggest that this regimen is effective for patients with squamous cell
      carcinoma of the esophagus.

PMID- 7574786
TI  - [Prophylactic intra-arterial chemotherapy for CR patients with invasive bladder
      cancer after induction therapy].
AB  - Thirteen patients with invasive bladder cancer treated by induction intra
      arterial chemotherapy in combination with radiotherapy achieved a complete
      response (CR). All of them were treated by prophylactic intra-arterial
      chemotherapy using pirarubicin (10), epirubicin (2) and carboplatin (1). The
      treatment was given once a month for 2 years. In the followup period from 14 to
      43 months (median; 22.5 months), only one of the 13 patients had an invasive
      recurrence of bladder cancer and died of it. Ten of the 13 patients are now
      disease-free and alive with functional bladder. The complications of this therapy
      were mild and tolerable. The results suggest that prophylactic intra-arterial
      chemotherapy is a useful regimen for CR patients with invasive bladder cancer
      after induction therapy.

PMID- 7574787
TI  - [The efficacy of several kinds of treatment for advanced hepatocellular carcinoma
      -a report of an over-five-year survivor by regional and systemic chemotherapy and
      adjuvant surgery].
AB  - We encountered a 53-year-old male patient with advanced hepatocellular carcinoma
      (HCC) uncontrolled by transcatheter arterial embolization (TAE). Numerous tumors
      with a huge one occupying the lateral segment were shown on abdominal
      ultrasonogram, computed tomogram and angiogram. The first TAE was ineffective for
      the lesions because of the development of collateral feeders. Lateral
      segmentectomy and, "wrapping therapy" for the liver remnant were performed, and
      catheters were put both into the hepatic artery and into the portal vein for
      regional chemotherapy. About a year after the procedure, anticancer drugs were
      administered. When tumor stains were found by following computed tomography or
      angiography, TAE was performed. The patient has survived for five years and four
      months. The combination of several kinds of treatment serves to improve the
      prognosis of patients with advanced HCC if the liver function is preserved.

PMID- 7574788
TI  - [Two hepatocellular carcinoma patients with biloma after transarterial
      embolization with lipiodol (Lip-TAE) leading to occlusion of portal vein].
AB  - We presented two patients with post-Lip-TAE biloma resulting in portal occlusion,
      and reviewed 20 previous studies including our cases to investigate their
      clinical characteristics. Case 1. A 31-year-old woman suffered from an HCC
      located at the S8 segment, and had a superselective embolization of feeding
      arteries using 3 ml of Lip, 300 mg of CBDCA, and 40 mg of Epi-Adriamycin (Epi
      ADM). Eleven weeks later, CT showed multiple cystic lesions, and the percutaneous
      transhepatic drainages of the lesions were established. At 21 weeks after Lip
      TAE, we found occlusion of the right branch of portal vein on CT, but she
      recovered from this condition, and was discharged 1 year later. Case 2. A 62-year
      old man was diagnosed as HCC located at S7-6 segments, and was infused with 3 ml
      of Lip, 150 mg of CBDCA, and 30 mg of Epi-ADM through a right hepatic artery. Ten
      weeks later, CT showed a cystic lesion in the S7-8 segments, occlusion of the
      right anterior segmental branch of the portal vein, and the same drainage was
      also established. Unfortunately, he died of liver failure 18 weeks later. In the
      literature, biloma after Lip-TAE occurred at 71.2 mean days, ranging from 7 to
      180 days, a with remarkable increase in biliary tree-associated enzymes. Seven
      (35%) of 20 patients died of liver failure or sepsis during 3 weeks and 1 year,
      and 3 (60%) of 5 patients accompanied by occlusion of a certain portal branch
      frequently died. We consider that these patients need intensive care and should
      be under long follow-up.

PMID- 7574789
TI  - [A case of multiple liver metastasis from ileac carcinoid effectively treated
      with continuous intraarterial infusion of somatostatin analog].
AB  - We report a case of multiple liver metastasis from ileac carcinoid treated with
      continuous intraarterial infusion of somatostatin analog. A 65-year-old man who
      complained of chest pain was admitted to Yamaguchi University Hospital School of
      Medicine for further examination of cardiac angina. Liver tumors, which were
      detected during ECHO cardiogram examination, were diagnosed as metastasis from
      carcinoid by percutaneous transhepatic liver biopsy. Primary tumor was found at
      the ileum by colonofiberscopy. We performed ileo-cecal resection and
      catheterization from the gastroduodenal artery for intraarterial chemotherapy
      under laparotomy. After the operation, the patient was treated with continuous
      intraarterial infusion of somatostatin analog (100 micrograms/day, 5 days/week
      for 16 weeks). The tumor in segment 6 (S6) disappeared, but the tumor in S2
      enlarged after the therapy. Hepatic angiography confirming the drug distribution
      demonstrated the occlusion of the left hepatic artery. This drug was thus
      distributed to the tumor in S6 but not in S2. These results suggest that
      somatostatin analog may have a direct anti-tumor effect. Furthermore, no side
      effect was observed. Thus, intraarterial infusion of somatostatin analog may be a
      useful therapy for liver metastasis from carcinoid.

PMID- 7574790
TI  - [A case of intrahepatic infusion chemotherapy with angiotensin II human for liver
      metastasis from early gastric cancer].
AB  - A 71-year-old woman underwent subtotal distal gastrectomy for II a+ II c type
      early cancer of the gastric antrum. Histological type was poorly differentiated
      adenocarcinoma with medullary proliferation, and the lesion invaded the
      submucosal layer. Two years and 6 months after the operation, multiple liver
      tumors were found on the CT scan. A surgical resection of the liver tumor was
      performed. Microscopically, the liver tumors were compatible with gastric cancer.
      The remnant liver metastases were treated by intrahepatic infusion chemotherapy
      with Angiotensin II human (Delivert) using a subcutaneous implanted pump. The
      liver metastases disappeared on the CT scan after 3 courses of chemotherapy, but
      bone metastasis occurred after 2 months. This mode of chemotherapy was therefore
      considered a useful treatment for liver metastasis in gastric cancer. We
      concluded that not only intrahepatic infusion chemotherapy with Angiotensin II
      human but also another systemic chemotherapy was necessary to treat patients with
      liver metastasis in gastric cancer.

PMID- 7574791
TI  - [Long-term survival in two cases of multiple liver metastasis successfully
      treated with intraoperative ultrasound-guided microwave tumor coagulation (MTC)].
AB  - Since April 1990, multiple metastatic liver tumors have been treated with
      intraoperative ultrasound-guided microwave tumor coagulation (MTC) in combination
      with postoperative intraarterial chemotherapy. Twenty-four patients have been
      enrolled in this therapeutic modality and two of five patients treated in 1990
      achieved long-term survival. In case 1, a 67-year-old woman was diagnosed as
      bearing gastric leiomyosarcoma with multiple liver metastasis. Total gastrectomy
      was performed, and six hepatic lesions were treated by MTC along with
      implantation of an intraarterial reservoir. Postoperative intraarterial
      chemotherapy was administered in a selective or subselective manner. Her survival
      time was 4 years and 6 months. In case 2, a 47-year-old man was diagnosed as
      having liver metastasis from descending colon cancer 1 year and 5 months after
      left hemicolectomy. When he was laparotomized for the treatment of adhesive
      ileus, three metastatic liver tumors were treated with MTC. Afterward, he
      underwent hepatic resection, intraarterial and intraportal chemotherapy. He
      survived for 5 years and 5 months after being diagnosed with liver metastasis.
      MTC is one of the useful modalities for the treatment of multiple liver
      metastasis.

PMID- 7574792
TI  - [Sclerosing cholangitis-induced biliary cyst formation: complication of hepatic
      artery infusion chemotherapy].
AB  - A 60-year-old man underwent resection of a sigmoid colon adenocarcinoma, left
      hepatic lobe, part of segment 6 and 8, due to its metastasis. He received hepatic
      artery infusions of 5-FU total amount, 15.5 g. There was no recurrence in the
      liver, but he developed sclerosing cholangitis, and a large biliary cyst formed
      in segment 8. After drainage of the cyst by percutaneous-trans-hepatic approach,
      bile leakage persisted, and liver dysfunction was progressive. Sclerosing
      cholangitis-induced biliary cyst formation is rare. Occlusion, or necrosis of the
      peripheral bile duct may be the cause.

PMID- 7574793
TI  - [Two cases of catheter tip dislocation to the duodenal bulb: a rare complication
      of hepatic arterial infusion chemotherapy].
AB  - Case 1: A 63-year-old woman underwent transverse colectomy and hepatectomy for
      colonic cancer and liver metastasis. A hepatic arterial infusion port (HAIP) was
      implanted. Continuous infusion of 5-FU (total amount, 7,500 mg) caused a
      hemorrhagic duodenal ulcer 15 months after. Follow-up endoscopy revealed the
      catheter tip was in the duodenal bulb. Case 2: A 62-year-old man underwent
      abdominoperineal resection for rectal cancer. Repeated hepatectomy for liver
      metastases was performed at 3 and 5 years after the first operation. HAIP was
      implanted at the last operation, but was not available at all due to the wound
      infection. The port was removed, but the catheter remained. Three years after,
      the catheter tip was found in the duodenal bulb by endoscopy.

PMID- 7574794
TI  - [A case report of far advanced gastric cancer with multiple liver metastasis (H3)
      treated with transarterial intermittent chemotherapy and intradermal
      administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea
      agglomerans].
AB  - A case of far advanced gastric cancer with multiple liver metastasis (H3) was
      treated with transarterial intermittent chemotherapy (5-FU: 250 mg/week,
      Farmorubicin: 10 mg/4 weeks, MMC: 4 mg/2 weeks) and intradermal administration of
      low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans. The
      CT examination and endoscopy showed regression of the tumor and the patient was
      discharged from the hospital. LPSp was given at the concentration of 0.1
      microgram initially, and the dose was gradually increased. Finally, the dose of
      LPSp was increased up to 70 micrograms. No serious side effect except fever was
      observed. The serum TNF-alpha levels were elevated and, histologically, CD 8(+)
      lymphocyte dominantly infiltrated around the tumor. These findings clearly
      indicated the immunological anticancer effect of LPSp. Intradermal administration
      of LPSp is a promising new adjuvant therapy to improve QOL without serious side
      effect.

PMID- 7574795
TI  - [A case report of prostate cancer resistant to endocrine therapy successfully
      treated with intra-arterial chemotherapy].
AB  - A 73-year-old male with low abdominal pain on urination and frequent urination
      was diagnosed as poorly differentiated adenocarcinoma of prostate. He received
      endocrine therapy with DESD and bilateral orchiectomy. This treatment was not
      effective, so he was given intra-arterial infusion chemotherapy with MTX, ADM and
      CDDP using the reservoir system. After 2 courses of this chemotherapy the
      regression rate was 75%, and the pathological examination after the chemotherapy
      revealed no cancer cells. There is no established chemotherapy for prostate
      cancer at present. Thus this case is very suggestive for the treatment of
      prostate cancer.

PMID- 7574796
TI  - [Chronochemotherapy in two cases of metastatic liver cancer].
AB  - Chronochemotherapy was performed in two cases of metastatic liver cancer. One was
      a 51-year-old woman whose pancreas tumor was incompletely removed six months ago
      and had a residual pancreas tumor (30 x 20 mm2) with liver metastases in S4.
      Another was a 54-year-old woman whose sigma colon cancer had been removed 10
      months ago. A large metastatic tumor in the fourth section of the liver and
      multiple daughter tumors in other parts of the liver were seen. The hyperthermic
      chemotherapy using warmed 5% glucose solution administered intraarterially could
      not be used for these patients. The variable rate of infusion of 5FU (250
      mg/body) and CDDP (3.3 mg/body) (23:19:00-7:00) (1/3:7:00-10:00) as chronotherapy
      showed more efficacy as an anti-cancer treatment compared to their continuous
      infusion.

PMID- 7574797
TI  - [A case of histological complete remission by preoperative intraarterial infusion
      chemotherapy].
AB  - We experienced a case of histological complete remission by preoperative
      intraarterial infusion chemotherapy in the treatment of histologically diagnosed
      endometrial cancer of well differentiated type. MRI demonstrated invasion of the
      myometrium to a depth of more than 1/2 and left partial parametrium. This patient
      was given intra-uterine arterial infusion chemotherapy twice (CDDP & ADM ia, CPA
      iv). Radical hysterectomy was done 3 weeks after intraarterial infusion
      chemotherapy. The extirpated uterus was histologically complete remission. Thus,
      in this case shows that intraarterial infusion chemotherapy is effective for neo
      adjuvant chemotherapy of endometrial cancer.

PMID- 7574798
TI  - [A case report: complete remission of stage IV uterine cervix carcinoma by immuno
      chemotherapy with intraarterial infusion using implantable reservoir system].
AB  - A patient with neck lymph node metastasis from squamous carcinoma of the uterine
      cervix was treated by immunotherapy and neo-adjuvant intraarterial infusion
      chemotherapy (OK-432 ic, etoposide 25 mg/body x 7 days po, CDDP 100 mg/m2/5 hr
      iA, CPM 200 mg/body iv, THP 50 mg/m2/2 hr iA). Three courses of the neo-adjuvant
      chemotherapy were given. After the first course, the neck metastatic tumor
      appeared remarkably small. After the second, the neck tumor disappeared and the
      uterine tumor appeared small and to have good movement. Hysterectomy was
      performed one month after. Each tissue platina concentration (microgram/cm3) is
      9.12 uterus cervix, 10.9 uterus corporis, 8.17 fallopian tube, 14.0 ovarium, 1.47
      0.88 pelvic lymph node. This patient was treated with irradiation after
      operation, and is presently in a state of cytological complete remission. Now she
      continues maintenance immunochemotherapy with UFT and OK-432 with a home doctor.

PMID- 7574799
TI  - [A case of malignant fibrous histiocytoma treated with intraarterial chemotherapy
      under complete venous isolation and charcoal hemoperfusion].
AB  - Herein reported is a case with malignant fibrous histiocytoma (MFH) at the left
      elbow treated successfully with intraarterial chemotherapy under complete
      brachial venous isolation and charcoal hemoperfusion (BVI-CHP). A 56-year-old man
      was admitted to our institution because of local recurrence at the left elbow 6
      months after extended local resection combined with systemic chemotherapy. We
      treated the patient with a 15-min intraarterial infusion of adriamycin (100
      mg/body) and cisplatin (30 mg/body) under a concomitant 30-min BVI-CHP. Two weeks
      after the first treatment, he received a repeated intraarterial infusion of
      adriamycin (80 mg/body) and cisplatin (50 mg/body) under BVI-CHP. The tumor
      became necrotic one week after the first treatment, resulting in 60% reduction in
      tumor diameter. In addition, angiography demonstrated a remarkable shrinkage of
      the tumor stain. Despite repeated intraarterial high-dose infusions of
      chemotherapeutic agents, systemic toxicities, such as leukopenia, nausea/vomiting
      and alopecia, were not observed. These results indicate that this approach offers
      a novel therapeutic option for malignant tumors in the extremities.

PMID- 7574800
TI  - [A case of multiple liver metastases of breast cancer treated successfully with
      high-dose intraarterial chemotherapy under hepatic venous isolation and charcoal
      hemoperfusion (HVI-CHP)].
AB  - The patient was a 53-year-old woman who underwent a standard radical mastectomy
      for right breast cancer five years ago and was recently referred to our hospital
      with a complaint of abdominal fullness. Systemic chemotherapy (CMFS) was
      performed based on the diagnosis of multiple liver metastases of the breast
      cancer, but its effect was unsatisfactory. In this case, we gave her high-dose
      intraarterial chemotherapy under HVI.CHP for metastatic liver tumors. Although
      slight elevation of serum GOT and GPT levels and leucopenia (1,800/mm3) were
      observed, alopecia did not occur throughout the posttreatment course. The levels
      of tumor markers including CEA, NCC-ST439 and CA15-3 showed remarkable
      reductions; CEA (ng/ml): 18.4-->3.0, NCC-ST439 (U/ml): 33.0-->2.4, CA15-3(U/ml):
      137.9-->26.3. Abdominal CT scan after the treatment demonstrated remarkable
      regression of liver metastases, showing a partial response (volume reduction:
      61%). In conclusion, HVI.CHP achieved a significant reduction in systemic drug
      exposure and allowed dose intensification of adriamycin during intraarterial
      chemotherapy. Therefore, we consider that high-dose intraarterial chemotherapy
      under HVI.CHP offers an effective therapeutic option for multiple liver
      metastases of the breast cancer.

PMID- 7574801
TI  - [Cell cycle regulation by anticancer agent].
AB  - Some anticancer agents induce cell cycle arrest. We analyzed the effect of
      anticancer agents on cell-cycle regulators, such as CDK. Our data suggested that
      arresting cells in the G2-phase of the cell cycle by cisplatin might be regulated
      by dephosphorylation of cdc2 kinase. Butyrolactone I inhibits both cdc2 and CDK2
      kinase in the cell-free system. The cytotoxic effect of paclitaxel shows mainly
      in the M-phase of the cell cycle. Suramin inhibits cdc2 kinase. UCN-01, a protein
      kinase-C inhibitor, also inhibits both cdc2 and CDK2 kinase. Some anticancer
      agents induce apoptosis.

PMID- 7574802
TI  - [High dose chemotherapy followed by hematopoietic stem cell transplantation for
      malignant lymphoma].
AB  - The role of high dose chemotherapy followed by hematopoietic stem cell
      transplantation in malignant lymphoma is discussed in comparison with the present
      state-of-the-art chemotherapy. Very recently, Parma randomized study revealed the
      apparent survival advantage of high dose chemotherapy in relapsed aggressive
      lymphoma patients who showed chemosensitivity to DHAP salvage therapy. Another
      randomized study conducted in UK showed the efficacy of high dose chemotherapy in
      relapsed or recurrent Hodgkin's disease. Therefore, it is generally accepted that
      patients with aggressive lymphoma or Hodgkin's disease who are chemosensitive to
      salvage chemotherapy at relapse are appropriate candidates for high dose
      chemotherapy. Although it is unclear that those with high-risk aggressive
      lymphoma will benefit from high dose chemotherapy in an up front setting, this
      strategy is expected to be the most promising one at the present time to improve
      the poor prognosis of such patients. To determine the exact role of high dose
      chemotherapy in malignant lymphoma and address the various questions, consecutive
      well-designed clinical trials should be conducted.

PMID- 7574803
TI  - [Autologous hematopoietic stem cell transplantation for the treatment of breast
      cancer].
AB  - To obtain higher anti-tumor efficacy for breast cancer (BC), high-dose
      chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) and
      peripheral blood stem cell transplantation (PBSCT) is believed to be one of most
      effective strategies. PBSCT shows earlier hematological recovery comparing with
      ABMT, therefore HDC could be performed more safety to introduce PBSCT in the
      treatment of BC. Several investigators have reported that higher complete
      response (CR) rate and continuously CR rate were obtained to employ HDC in the
      earlier course of treatment for patient with advanced or recurrent BC responding
      to standard-dose chemotherapy. The efficacy of HDC has been also observed in
      adjuvant setting for patient with high-risk (> or = 10 axillary lymph nodes)
      after mastectomy. Phase III studies will clarify the efficacy of HDC with ABMT,
      PBSCT for the treatment of BC in near future.

PMID- 7574804
TI  - [Mega-dose chemotherapy with peripheral blood stem cell transplantation (PBS-CT)
      for small cell lung cancer (SCLC)].
AB  - Feasibility and the efficacy of mega-dose chemotherapy with peripheral blood stem
      cell transplantation (PBSCT) for small cell lung cancer (SCLC) were evaluated.
      Autologous peripheral blood stem cell (APBSC) was collected after induction
      chemotherapy (Extensive disease: CDDP+etoposide+ADM, Limited disease:
      CDDP+etoposide) followed by the administration of granulocyte colony stimulating
      factor (G-CSF). Five cases of ED and 2 cases of LD have been entered in the
      protocol so far. PBSC was harvested after the second course of induction
      chemotherapy, and a sufficient number of PBSC (CFU-GM > or = 1 x 10(5)/kg) could
      be harvested and cryopreserved in all 7 cases. After completion of 4 courses of
      induction chemotherapy, three patients who achieved CR or good PR were treated by
      the combination of CBDCA (1,600 mg/m2) plus etoposide (1,600 mg/m2) followed by
      APBSCT and G-CSF. Hematologic recovery after APBSCT was rapid (absolute
      granulocyte count > 500/microliters: 9-11 day, Plt > 3 x 10(4)/microliters:10-14
      day) and no infectious episode nor bleeding tendency occurred throughout the
      treatment period. Although grade 3 gastrointestinal toxicity was seen in one
      patient, the mega-dose chemotherapy with APBSCT in SCLC was considered safe and
      feasible. Further clinical trials are needed to establish the role of mega-dose
      chemotherapy for the treatment of SCLC.

PMID- 7574805
TI  - [Germ cell tumor].
AB  - Germ cell tumor (GCT) is chemotherapy-sensitive, and with the development of a
      cisplatin combined regimen, the majority of patients can now be cured. Seventy
      percent to 80% of patients with advanced GCT have a lasting complete response to
      a cisplatin combined regimen, while 20 to 30% of these patients are refractory to
      the therapy. Refractory GCT patients need more effective and intense therapy. In
      order to overcome the conventional dose chemotherapy results, high-dose
      chemotherapy backed by autologous hematopoietic stem cell transplantation
      (AHSCT), has been applied to patients with GCT who have relapsed after achieving
      a complete response by first-line chemotherapy or to those in whom disease
      progression or the failure to achieve CR had occurred after initial and/or
      ifosfamide combined salvage therapy. The therapy with a high-dose combination of
      CBDCA (Carboplatin), VP-16 (Etoposide) and CPM (Cyclophosphamide) or IFM
      (Ifosfamide), supported with AHSCT is administered to the advanced GCT patients.
      The response rate (CR+PR) ranges from 40 to 78% by reported groups averaging
      about 50%, and disease-free survival is possible in about half the survivors thus
      far. Treatment related morbidity and mortality are observed, but are tolerable
      with the above dosage. Thanks to the technical development of collecting
      hematopoietic stem cells using either bone marrow or peripheral blood, and
      hematopoietic growth factor to lessen hematologic toxicities and obtain early
      hematological recovery, this method can be performed more safely. High-dose
      chemotherapy with AHSCT may well become more effective in patients with resistant
      GCT by a new combination of synergistic drugs or multicycle transplants.

PMID- 7574806
TI  - [High-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation
      (PBSCT) in ovarian cancer patients with poor prognosis].
AB  - Platinum is a key drug in ovarian cancer chemotherapy. Through combination with
      peripheral blood stem cell transplantation (PBCST), up to three times the usual
      carboplatin dose (1,200 mg/m2) may be given. If granulocyte colony stimulating
      factor (G-CSF) is added to the PBSCH harvest and apheresis is performed twice
      when the leukocyte count exceeds 10,000/microliters 14 days before and after the
      platinum-based chemotherapy, the necessary hematopoietic stem cell collection for
      bone marrow reconstitution can be done. This treatment proves most effective when
      the initial treatment is under way and it is used as a consolidation therapy for
      minimum residual disease very similar to PCR or for PCR itself. Forthcoming
      investigation should determine what impact this therapeutic approach will have on
      longer survival, or whether it will contribute to treatment of an ovarian cancer
      with a poor prognosis, for example, when the residual tumor measures more than 2
      cm in diameter. Moreover, what results can be expected if one uses effective ip
      chemotherapy with the standard dose in conjunction with the PBSCT-HDCT
      combination? Especially, if one can contact the residual tumor in the
      intraperitoneal cavity most likely to have a recurrence with a drug at an
      extremely high concentration, enabling a massive dose to the intraperitoneal
      cavity comparable to the standard dosage by vas internal administration with
      equivalent blood concentration, distant metastases may also be prevented.

PMID- 7574807
TI  - [Myeloablative chemotherapy with autologous bone marrow and/or peripheral blood
      stem cell transplantation in children with high-risk solid tumor].
AB  - Autologous bone marrow transplantation (ABMT) and peripheral blood stem cell
      transplantation (PBSCT) are increasingly used to support high-dose chemotherapy
      for solid tumors of childhood. In this review we described practical aspects of
      myeloablative chemotherapy rescued by ABMT, PBSCT or combination of ABMT and
      PBSCT for the treatment of children with high-risk solid tumor, involving our
      experiences in 15 cases. Indication, method of harvesting bone marrow and
      peripheral blood stem cells, cryopreservation, transplantation, selection of anti
      neoplastic agents for preconditioning, nutritional and G-CSF support, engraftment
      and outcomes for prognosis were discussed. In comparing the engraftment of stem
      cells between ABMT and PBSCT, the acceleration of platelet and erythrocyte
      recovery is less impressive, although there is a tendency to more rapid recovery
      of granulocyte in PBSCT group. The outcomes are distinctly improved only in
      patients who showed complete remission after induction chemotherapy, radiation
      and surgical excision. A better prognosis will be conferred especially in
      neuroblastoma and entities of small round cell tumor. It is noteworthy that
      relapses can occur as distant metastasis considerable years after complete
      clinical remission. This may be largely contributed by contaminated malignant
      cells in both harvested bone marrow and peripheral blood stem cells. There is no
      significant difference between the relapse rates after ABMT and PBSCT.

PMID- 7574809
TI  - [Chemosensitivity test for thyroid cancer by in vitro MTT assay].
AB  - In vitro MTT assay was applied for examining chemosensitivity with 50 thyroid
      cancers; 47 papillary cancers, 1 follicular cancer, 1 anaplastic cancers, and 1
      medullary cancer. Anticancer drugs examined were 5-fluorouracil (5-FU), cisplatin
      (CDDP), adriamycin (ADM), etoposide (VP-16) and ifosfamide (IFO) (active type).
      Their efficacy was as follows: 5-FU 0%, CDDP 40.9%, ADM 0%, VP-16 5.3%, IFO
      48.5%. Anaplastic cancer and medullary cancer showed no sensitivity to all tested
      drugs. We compared the chemosensitivity between cancer tissue and normal tissue.
      CDDP was more effective in cancer tissue than in normal tissue. Chemosensitivity
      of CDDP depended on the drug concentration but 5-FU did not. CDDP and IFO might
      be useful against human differentiated thyroid cancer.

PMID- 7574808
TI  - [High-dose chemotherapy with autologous bone marrow transplantation or peripheral
      blood stem cell transplantation--testicular cancer].
AB  - Through advances in chemotherapy with the appearance of the drug cisplatin,
      testicular cancer treatment has improved dramatically. Consequently, testicular
      cancer has become one of the group of tumors that can be completely cured. Even
      in advanced testicular cancer, a curative rate of approximately 70% is obtainable
      from first-line chemotherapy, commonly by BEP combination. The problem, however,
      is treatment of the remaining 30% of the patients who fail to respond to first
      line chemotherapy or who relapse shortly after first-line chemotherapy.
      Supportive therapy strengthens the chemotherapy of testicular cancer, for
      example, high-dose chemotherapy with carboplatin and etoposide with autologus
      bone marrow rescue, either by autologus bone marrow transplantation or peripheral
      blood stem cell transplantation, which can cure 15% to 20% of patients whose
      disease has progressed during prior chemotherapy combined with cisplatin. Though
      more cases of relapse were observed with high-dose chemotherapy compared to first
      line chemotherapy, and the long-term prognosis is unknown, we should evaluate the
      usefulness of high-dose chemotherapy as an initial treatment for testicular
      cancer patients with poor prognoses.

PMID- 7574810
TI  - [Pharmacokinetics of SK & F 104864 in experimental animals. I. Plasma level].
AB  - A camptothecin derivative, SK & F 104864 (topotecan), was injected for 30 minutes
      into the rabbit ear vein at a dose of 2 mg/kg or 5 mg/kg, and the plasma
      concentration was assayed by a HPLC method. The plasma level of SK & F 104864
      (lactone form) decreased bi-exponentially with mean alpha and beta half-lives of
      0.101 h and 0.849 h at 2 mg/kg, respectively, and 0.518 h and 7.57 h at 5 mg/kg,
      respectively. The AUCs were 0.846 micrograms.h/ml at 2 mg/kg and 2.14
      micrograms.h/ml at 5 mg/kg. The plasma level of total topotecan (SK & F 104864
      plus SK & F 105992) decreased bi-exponentially with mean alpha and beta half
      lives of 0.696 h and 9.07 h at 2 mg/kg, respectively, and 0.795 h and 8.97 h at 5
      mg/kg, respectively. The AUCs were 2.15 micrograms.h/ml at 2 mg/kg and 5.73
      micrograms.h/ml at 5 mg/kg. The AUCs of lactone form were 39.3% of total
      topotecan at the 2 mg/kg dose and 37.3% at the 5 mg/kg dose, respectively. After
      intravenous bolus injection of SK & F 104864 at 20 mg/kg into Sarcoma 180 bearing
      mice, the alpha and beta half-lives of SK & F 104864 were 0.401 h and 3.99 h,
      respectively, and the AUC was 5.49 micrograms.hr/ml. The alpha and beta half
      lives of total topotecan were 0.517 h and 4.27 h, respectively, and the AUC was
      9.88 micrograms.hr/ml. The ratio of lactone form to total topotecan was 55.6%.

PMID- 7574811
TI  - [Pharmacokinetics of SK & F 104864 in experimental animals. II. Tissue
      distribution].
AB  - After intravenous bolus injection of a camptothecin derivative, SK & F 104864
      (topotecan), at 20 mg/kg into Sarcoma 180 bearing mice, the tissue concentration
      of total topotecan (SK & F 104864 plus SK & F 105992) in the mice decreased bi
      exponentially, and the beta half-lives in most tissues were longer than those in
      plasma. The AUCs of total topotecan were extremely large in the kidney, that was
      followed by the pancreas > intestine > stomach > spleen > liver > thymus > lung >
      tumor > uterus > plasma. The concentration of total topotecan after 24 hours
      decreased to less than 2% of the peak level in most tissues except the kidney.

PMID- 7574812
TI  - [Combination therapy of doxifluridine, pirarubicin and cisplatin for human
      gastric cancers implanted in nude mice].
AB  - In the preclinical study of a new combination therapy for gastric cancer, dFTP,
      consisting of doxifluridine (5'-DFUR), pirarubicin (THP) and cisplatin (DDP) as a
      modification of conventional FAP regimen (5-fluorouracil+Adriamycin+DDP), we
      compared antitumor and toxic effects of two sequential treatment schedules,
      single injection of DDP before or after 4 daily administrations of 5'-DFUR, on 5
      strains of human gastric cancer bearing nude mice. Results indicated that both
      schedules of the dFTP regimen had potent antitumor effects. There was no
      significant difference between them. On the other hand, in terms of the host
      toxicity as observed by body weight loss, the post-DDP schedule was significantly
      less toxic than pre-DDP. These results suggest that dFTP regimen (post-DDP
      schedule) may be useful for clinical treatment of gastric cancers.

PMID- 7574813
TI  - [Combination therapy of high dose 5'-DFUR+MMC for advanced or recurrent gastric
      cancer. 5'-DFUR Joint Research Group in the Osaka District for Gastric Cancer].
AB  - We conducted multi-center clinical trials of 'Treatment with high dose 5'
      DFUR+MMC' in order to evaluate the effects, the possibility for outpatient
      treatment and the survival effects in patients with advanced or recurrent gastric
      cancer. The treatment schedule was as follow; 5'-DFUR 1,600 mg/body/day was given
      orally for five consecutive days every week and MMC 6 mg/m2 was injected
      intravenously once every four weeks. Forty-eight patients were enrolled and 34
      cases were evaluated for anti-tumor responses. The overall response rate was
      29.4% (10/34 cases). Side effects were mainly diarrhea, but outpatient treatment
      was possible in most cases. The median survival period was 249 days, which is
      longer than with other treatments. This result suggests that this combination
      chemotherapy is useful in patients with advanced or recurrent gastric cancers.

PMID- 7574814
TI  - [A prospective randomized clinical trial comparing intra-arterial chemotherapy
      alone and when combined with hyperthermia for metastatic liver cancer].
AB  - To evaluate the efficacy of intra-arterial chemotherapy combined with
      hyperthermia for metastatic liver cancer, our cooperative study group carried out
      a randomized clinical trial comparing intra-arterial chemotherapy alone and intra
      arterial chemotherapy combined with hyperthermia. Patients were treated with
      combined chemotherapy of epirubicin (EPIR), mitomycin C (MMC), 5-fluorouracil (5
      FU), by hepatic infusion using a subcutaneously implanted reservoir. Hyperthermia
      (8MHz radiofrequency) was usually performed for 40-60 min every week, and intra
      arterial chemotherapy was performed immediately before hyperthermia. Twenty-six
      patients were registered by telephone contact and allocated at random to groups
      treated with either intra-arterial chemotherapy alone (14 patients) or
      combination therapy (12 patients). The response rate was 7% in the chemotherapy
      alone group (1 PR among 14 evaluable patients), and 40% in the combination
      therapy group (4 PR among 10 evaluable patients). Our results suggest that intra
      arterial chemotherapy combined with hyperthermia is a useful modality for the
      treatment of metastatic liver cancer.

PMID- 7574815
TI  - [Light and electron microscopic examination compared to evaluation by tumor size
      in subrenal capsule assay for chemosensitivity testing in esophageal cancer].
AB  - Specimens from six clinical cases of esophageal cancer were transplanted under
      the renal capsule of AF nude mice, and chemosensitivity to anticancer drugs (UFT,
      CDDP) was evaluated by measuring tumor size (SRC). Histological analysis of the
      xenografts by light (LM) and electron microscopy (EM) was also performed to
      confirm the precision of this original method used for SRC. Two-dimensional
      morphometry by EM was also performed in four cases. With the exception of one
      case, the same results were obtained by graft measurement analysis and light
      microscopic observation, which allowed easy evaluation by observing cancer pearl
      formation, prominent proliferation of tumor cells or total cell keratinization.
      However, there was no false-positive sensitivity in the former method. EM
      observation did not reveal any special findings with regard to chemotherapy
      response, but increased numbers of cytoplasmic vacuoles and desmosomes,
      cytoplasmic swelling, a reduction of the N/C ratio and nuclear deformity implied
      common changes to cell necrosis induced by the anticancer drugs. For clinical use
      of SRC against esophageal cancer, it is supposed to be best to compare LM
      histological evaluation, which is too complicated and time consuming. For this
      reason, it is potentially useful to perform SRC by evaluating tumor size, because
      another goal of chemosensitivity testing involves determination of anticancer
      drugs without effectiveness.

PMID- 7574816
TI  - [A comparative study of the effect of granisetron and a combination of
      granisetron plus steroids on cancer chemotherapy induced emesis].
AB  - Effects of 40 micrograms/kg of granisetron monotherapy (K group) and concurrent
      therapy with a steroid (KS group) on acute and delayed emesis induced by cancer
      chemotherapy which included CDDP at a dose of 60 mg/m2 or more were compared in
      random clinical trials under the central registration method. In KS group, either
      500 mg of methylprednisolone succinate or 8 mg of dexamethasone phosphate was
      given prior to granisetron administration. Clinical symptoms such as vomiting,
      nausea and anorexia were better in KS group than in K group, on any day from day
      1 to day 7, and there was a statistically significant difference on day 1 and day
      2. The cumulative total control rate throughout the period of seven days was also
      significantly higher in KS group. KS group was rated higher in the final clinical
      evaluation based on doctor's impressions, but there was no significant difference
      between the two groups. Augmented antiemetic effect of granisetron by concurrent
      therapy with a steroid was most notably demonstrated in male patients under 60
      years of age. The antiemetic effect at the acute stage was proven to influence
      the final clinical effectiveness, thus suggesting the importance of antiemetic
      therapy of acute emesis. Adverse reactions were seen in two out of 122 patients
      (1.6%). They were slight headache and moderate diarrhea in 1 case each, both of
      which disappeared soon, confirming the high safety profile of granisetron.

PMID- 7574817
TI  - [Efficacy of treatment with frequent and low-dose epirubicin in two cases of
      pulmonary metastases after surgery of liver cancer].
AB  - Case 1 was a 55-year-old male with multiple pulmonary metastases after two
      operations to excise hepatocellular carcinoma. Treatment consisted of initial
      administration of 5'-DFUR (po), followed by frequent administration of low-dose
      epirubicin (20 mg/body once every 2 weeks iv). This resulted in disappearance of
      the pulmonary metastases and a striking decrease in the AFP level. Case 2 was a
      68-year-old male with multiple pulmonary metastases after surgery for
      hepatocellular carcinoma. Treatment with 5-FU (iv; once a week) and epirubicin
      (20 mg/body once every 2 weeks iv) resulted in disappearance of the pulmonary
      metastases and a marked decrease in the AFP level. It was concluded that
      administration of epirubicin in frequent, low doses is a useful method for the
      treatment of pulmonary metastasis after surgery for liver cancer, and it can be
      safely performed even on an outpatient basis.

PMID- 7574819
TI  - [A synchronous double cancer of esophagus and stomach treated with 5-fluorouracil
      and consecutive low-dose cisplatin].
AB  - We report a case of double cancer of esophagus and stomach treated with 5
      fluorouracil and consecutive low-dose cisplatin. The patient was a 58-year-old
      man with liver cirrhosis. Using upper gastrointestinal fiberscopy, a superficial
      depressed lesion (O-IIc) in the middle thoracic part of the esophagus and
      Borrmann 2 type lesion in the fundus of the stomach were also detected.
      Microscopic examination of the biopsy specimen revealed moderately differentiated
      squamous cell carcinoma and adenocarcinoma. But laparotomy could not be done due
      to impaired liver function (KICG 0.051, ICGR15 45.2%). The patient was treated
      for 28 days with continuous 24 hour infusion 5-FU, 250 mg/body/day plus low dose
      CD-DP, 10 mg/body daily by bolus infusion d1-5, 8-12, 15-19, 22-26. One month
      after the chemotherapy, both the gastric cancer and the esophageal cancer were
      remarkably reduced (diagnosis: PR), and showed no malignancy in the histology.
      There was no change in the histological findings of the esophageal lesion at 31
      months after the chemotherapy. This therapy is effective for patients with
      gastric cancer and esophageal cancer.

PMID- 7574818
TI  - [A case of advanced gastric cancer treated effectively with neo-adjuvant
      chemotherapy using l-leucovorin and 5-FU].
AB  - A 59-year old man was diagnosed as having advanced gastric cancer, liver
      metastasis and lymph node metastases after a closed medical examination. Because
      Schnitzler metastasis was also suspected, chemotherapy was started pre
      operatively. The schedule of administration was as follows. One course was l-LV
      250 mg/m2 and 5-FU 600 mg/m2 injected intravenously every week and continued for
      6 weeks. The UGI examination showed partial response in stomach cancer, and liver
      metastasis disappeared on CT-scan after 2 courses. We performed total
      gastrectomy, lymphadenectomy, splenectomy and partial resection of liver.
      Histological effects showed Grade 1a on main tumor, Grade 2 on liver metastasis,
      and No. 3 lymphnode metastasis. The survival time was 476 days.

PMID- 7574820
TI  - [A case of ovarian malignant Sertoli-Leidig cell tumor treated with CBDCA,
      etoposide and epirubicin chemotherapy].
AB  - A 49-year-old female presented with a low abdominal tumor. Before operation, she
      had neither evidence of androgen excess nor abnormal tumor marker values, but US,
      CT and MRI findings strongly suggested the possibility of a malignant ovarian
      tumor. Her operative findings were as follows: a goose egg-sized main tumor in
      the low abdomen, with a walnut-sized tumor in the right side, which grew around
      the right ureter, causing right non-functional kidney. Pathological examination
      revealed her tumor was a very rare type of malignant Sertoli-Leidig cell tumor
      with pelvic lymph nodes metastases. Most patients with this disease usually have
      good prognoses, but with metastasis or recurrence, no therapy is as effective as
      in epithelial ovarian cancer. In this case, we selected a new combination
      chemotherapy of CBDCA, Etoposide and Epirubicin, considering current changes in
      the chemotherapy for ovarian germ cell tumors and Sertoli-Leidig cell tumors of
      testis. Now, 1 year and 4 months after operation, she has no evidence of
      recurrence or metastasis. This study proposes a new, presumably more effective
      chemotherapy for an ovarian malignant Sertoli-Leidig cell tumor.

PMID- 7574821
TI  - [Combination chemotherapy with POMB/ACE (cisplatin, vincristine, methotrexate,
      bleomycin, actinomycin D, cyclophosphamide, etoposide) in advanced non
      seminomatous testicular tumor].
AB  - Four cases with non-seminomatous testicular tumor in stage III completed
      chemotherapy with POMB/ACE. Of these 4 cases, metastasis to retroperitoneal lymph
      nodes was found in all of them. In addition, metastasis to the lung was noted in
      3, and to the left supraclavicular lymph nodes in one. After orchiectomy, 5
      courses of POMB/ACE therapy were given to each of the 4 cases. Tumor marker
      returned to normal value in all of the cases after 3-4 courses of treatment, with
      disappearance of metastasis to the lung and supraclavicular lymph nodes. However,
      the response rate in metastasis to retroperitoneal lymph nodes was CR in one
      case, and PR in 3. Therefore, retroperitoneal lymph nodes were excised in all 3
      cases. Histologically, 2 of the 3 were found to have necrotic tissues. The
      remaining one patient had teratoma. An additional 1-3 courses of POMB/ACE therapy
      were given to these 3 cases. These 4 cases are alive without recurrence 6 years
      and 4 months, 5 years and 8 months, 4 years and 9 months, and 2 years 9 months,
      respectively, after orchiectomy. Thus POMB/ACE therapy is considered to be a
      useful method in the treatment of advanced testicular tumor.

PMID- 7574822
TI  - [Antibiotic and anti-cancer pasting for putrefactive cancers].

PMID- 7574823
TI  - [The experience of concurrent radiotherapy and chemotherapy for advanced or
      recurrent esophageal cancers--continuous infusion of 5-FU and low dose
      cisplatin].

PMID- 7574824
TI  - Fox-Fordyce disease treated with topical clindamycin solution.

PMID- 7574825
TI  - Bedsore of an unknown primary site.

PMID- 7574826
TI  - Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of
      hepatitis C virus-induced mixed cryoglobulinemia.
AB  - BACKGROUND AND DESIGN: Hepatitis C virus (HCV) infection is associated with mixed
      cryoglobulinemia, which can cause a vasculitis affecting various organs. To
      determine the prevalence of cutaneous vasculitis in patients infected with HCV,
      information concerning a series of 408 HCV antibody-positive outpatients was
      analyzed. Patients with a skin eruption were evaluated by a dermatologist for
      objective evidence of cutaneous vasculitis, and the sensitivity of cryoglobulins
      was compared with that of rheumatoid factor activity as a serologic marker of
      mixed cryoglobulinemia in these patients. RESULTS: Cutaneous vasculitis was
      identified in 10 of 408 HCV-infected patients (prevalence of at least 2%). The
      vasculitis was manifested as palpable purpura in eight patients, livedo
      reticularis in one patient, and urticaria in one patient. The skin eruption was a
      major presenting feature in each of the 10 patients and even led to the discovery
      of occult HCV infection in two patients. Histologic examination revealed
      leukocytoclastic vasculitis in six patients and necrotizing arteritis consistent
      with polyarteritis nodosa in two patients. All 10 patients had chronic active
      hepatitis and exhibited rheumatoid factor activity. Variable features
      attributable to mixed cryoglobulinemia included arthropathy, central nervous
      system abnormalities, and glomerular disease. Serum cryoglobulins were detected
      in only four patients. CONCLUSIONS: Practitioners should be alert to the
      possibility of HCV infection in patients presenting with palpable purpura, livedo
      reticularis, or urticaria, in which the underlying histologic features are those
      of leukocytoclastic vasculitis or necrotizing panarteritis. Positive serologic
      test results for HCV antibody and rheumatoid factor in such patients virtually
      confirm the diagnosis of HCV-induced mixed cryoglobulinemia.

PMID- 7574827
TI  - Essential mixed cryoglobulinemia. A comparative study of dermatologic
      manifestations in patients infected or noninfected with hepatitis C virus.
AB  - BACKGROUND AND DESIGN: An association between essential mixed cryoglobulinemia
      and hepatitis C virus (HCV) infection has been reported. Dermatologic
      manifestations are a classic presenting complaint in essential mixed
      cryoglobulinemia. The aim of this study was to compare the frequency and the
      nature of dermatologic manifestations in essential mixed cryoglobulinemia
      according to the presence of anti-HCV antibodies. Sixty-two consecutive patients
      with essential mixed cryoglobulinemia were tested for anti-HCV antibodies.
      Dermatologic manifestations were systematically assessed. RESULTS: Anti-HCV
      antibodies were detected in 35 patients. Palpable purpura corresponding
      histologically to leukocytoclastic vasculitis was the more frequently observed
      dermatologic manifestation and occurred mainly in HCV-antibody-positive patients.
      The patients with purpura had significantly higher serum cryoglobulin levels than
      patients without purpura. CONCLUSIONS: The frequency of palpable purpura is
      higher in HCV-antibody-positive patients and is related to the serum cryoglobulin
      levels.

PMID- 7574828
TI  - Prevention of UVB-induced immunosuppression in humans by a high sun protection
      factor sunscreen.
AB  - BACKGROUND AND DESIGN: To date, studies of the effectiveness of sunscreens in
      preventing UVB-induced suppression of contact hypersensitivity in humans have not
      been published. Several studies in mice of the protection afforded by sunscreens
      from UVB-induced suppression of contact hypersensitivity and rejection of
      transplanted skin cancers have yielded dissimilar results, ranging from "no" to
      "complete" protection. We sought to determine whether the effect of
      preapplication of a sun protection factor (SPF) 29 sunscreen (containing octyl
      methoxycinnamate, oxybenzone, and octyl salicylate) could prevent local UVB
      induced suppression of contact hypersensitivity to dinitrochlorobenzene (DNCB).
      Nineteen subjects received either three minimal erythema doses of UVB daily on
      three consecutive days (UVB group) or sunscreen followed by this same dose of UVB
      irradiation (sunscreen plus UVB group) to a 16-cm2 area of the buttock. One day
      after completion of irradiation, DNCB was applied to this buttock site, and 2
      weeks later, forearm challenge with four different concentrations of DNCB was
      performed. A control group of 10 subjects underwent DNCB testing as above, but
      with no prior exposure to UVB (no-UVB group). RESULTS: The UVB group had a
      reduced response rate to all challenge doses of DNCB (3.125, 6.25, and 8.8
      micrograms), except for the highest dose (12.5 micrograms) compared with the no
      UVB control group (Fisher's Exact test, P < or = .008), and compared with the
      sunscreen plus UVB group (P < or = .02). The no-UVB and sunscreen plus UVB groups
      showed no significant differences in response rates to any of the doses of DNCB
      tested (P > or = .53). CONCLUSIONS: These results indicate that application of a
      sunscreen with over ninefold greater protection than that needed to prevent
      erythema prior to localized UVB radiation prevents localized UVB-induced
      suppression of contact hypersensitivity. Further studies are needed to determine
      whether sunscreens providing less protection, yet still preventing erythema,
      adequately prevent suppression of contact hypersensitivity, a possible surrogate
      marker for skin cancer tumor antigen recognition and rejection.

PMID- 7574829
TI  - Skin type, but neither race nor gender, influence epidermal permeability barrier
      function.
AB  - BACKGROUND AND DESIGN: Previous studies that compared transepidermal water loss
      in subjects of different race and sex showed minimal differences in basal
      permeability barrier function. These studies often did not assess the ability of
      the stratum corneum to withstand or recover from insults to the epidermal
      permeability barrier. We compared epidermal permeability barrier function in the
      following human subjects (age range, 22 to 38 years): white (n = 8) vs Asian (n =
      6); male (n = 7) vs female (n = 7); and skin type II/III (n = 14) vs skin type
      V/VI (n = 7) (scale, I to VI). Basal transepidermal water loss was measured by
      evaporimetry (three sites) on the volar aspect of the forearm. Barrier integrity
      then was assessed by determining the number of tape strippings required to reach
      a transepidermal water loss greater than or equal to 20 g/m2 per hour. The rates
      of barrier recovery then were compared at 6, 24, and 48 hours and 1 week after
      abrogation. RESULTS: Neither the number of tape strippings required to perturb
      the barrier nor the rates of barrier recovery were significantly different in
      white vs Asian subjects or in female vs male subjects. However, patients with
      skin types II/III required only 29.6 +/- 2.4 tape strippings to perturb the
      barrier, while the skin type V/VI group required 66.7 +/- 6.9 tape strippings.
      Furthermore, while barrier function in skin type II/III recovered by
      approximately 20% by 6 hours and 55% by 48 hours, barrier function in skin type
      V/VI, independent of race, recovered more quickly, 43% and 72% at 6 and 48 hours,
      respectively. Finally, neither the differences in barrier integrity nor in rates
      of recovery could be attributed to variations in cohesiveness, since stripping
      appears to remove the same weight of stratum corneum in both groups. CONCLUSIONS:
      Darkly pigmented skin displays both a more resistant barrier and one that
      recovers more quickly after perturbation by tape stripping than does the skin of
      individuals with lighter pigmentation. These findings have potential implications
      for transdermal delivery of topical or systemic therapeutic agents, the ability
      of individuals with different skin types to withstand environmental or
      occupational insults, and the influence of acquired hyperpigmentation or pigment
      loss to influence permeability.

PMID- 7574830
TI  - Neutrophilic dermatoses during granulocytopenia.
AB  - BACKGROUND AND DESIGN: Noninfectious cutaneous neutrophilic lesions can occur
      during granulocytopenia, but their mechanism remains unknown. We undertook a
      retrospective study of the neutrophilic dermatoses that developed during
      granulocytopenia induced by chemotherapy for acute myelogenous leukemia. RESULTS:
      Seven men and one woman were included (2.6% of treated cases of acute myelogenous
      leukemia); half had acute myelogenous leukemia subtypes 4 and 5. The male-to
      female ratio was 7:1. Neutrophilic eccrine hidradenitis was diagnosed in five
      cases, Sweet's syndrome in two cases, and difficult-to-classify neutrophilic
      dermatoses in one case. Cutaneous lesions appeared 12.5 days after the start of
      chemotherapy, and the mean leukocyte count was 0.426 x 10(9)/L. Three patients
      needed corticosteroids systemically. CONCLUSION: Neutrophilic dermatoses during
      chemotherapy-induced granulocytopenia seem to occur more frequently in men with
      acute myelogenous leukemia subtypes 4 and 5.

PMID- 7574831
TI  - Cutaneous eruptions from suramin. A clinical and histopathologic study of 60
      patients.
AB  - BACKGROUND AND DESIGN: During a trial of suramin for advanced solid tumors, a
      high rate of cutaneous adverse reactions was observed. We present a prospective
      study, describing the clinical, histopathologic, histochemical, and
      immunochemical findings of the cutaneous reactions observed in 60 patients
      treated with suramin. RESULTS: Forty-nine (82%) of the 60 patients studied
      experienced at least one cutaneous reaction attributable to suramin therapy.
      Although morbilliform reactions predominated, a wide variety of eruptions was
      observed. Most reactions occurred within the first 24 hours of therapy and were
      self-limited despite continued drug infusion. Distinctive cutaneous findings
      included scaling erythematous papules (suramin keratoses) and a predilection of
      many eruptions for previously sun-exposed areas. Six patients experienced severe
      cutaneous reactions, but no patient permanently withdrew from therapy because of
      cutaneous toxic reactions. Common histopathologic findings included
      hyperkeratosis, parakeratosis, spongiosis, acanthosis, exocytosis, apoptosis, a
      perivascular lymphohistiocytic infiltrate, upper dermal edema, and increased
      dermal mucin. Staining with S100 antigen was markedly positive in several
      specimens. Only trace amounts of suramin were detected in skin samples tested
      with high-pressure liquid chromatography. CONCLUSIONS: The incidence of cutaneous
      toxic reactions from suramin greatly exceeds that seen with other medications. A
      wide spectrum of skin manifestations were observed, including suramin keratoses
      and UV recall, although serious reactions were infrequent. Cutaneous toxic
      reactions neither predicted nor correlated with other toxic reactions from
      suramin. Suramin may soon become more widely used; practitioners should be aware
      of the high incidence and wide spectrum of cutaneous toxic reactions to this
      drug.

PMID- 7574832
TI  - Comparison between familial and nonfamilial melanoma in France.
AB  - BACKGROUND AND DESIGN: Five percent to 10% of cutaneous malignant melanomas
      (CMMs) occur in a familial setting. Clinical, epidemiologic, and genetic studies
      of familial CMM in different regions of the world have led to various results. To
      assess the characteristics of familial CMM in France, the clinical, histologic,
      and epidemiologic characteristics of 295 patients with CMM were recorded, and a
      comprehensive familial investigation was performed for each case. Patients with a
      family history of CMM were compared with nonfamilial cases. RESULTS: Cutaneous
      malignant melanoma occurred as a familial cancer in 22 (8%) of 295 patients.
      Among the multiple variables studied, those significantly associated with the
      familial occurrence of CMM were red hair, inability to tan, and presence of
      clinically atypical moles. When these variables were considered together in a
      multivariate analysis, only the association with red hair (P = .001) and atypical
      moles (P < .05) remained significant. In addition, the patients with familial
      melanoma exhibited the following tendencies: a younger age at diagnosis, a higher
      number of moles, and the development of multiple primary melanomas, but these
      results did not reach statistical significance. Factors relating to UV light
      exposure, histologic features of CMM, course of the disease, and occurrence of
      nonmelanoma cancers showed a similar distribution between familial and
      nonfamilial cases. CONCLUSION: A familial investigation should be performed for
      each patient with CMM in France, particularly when he or she exhibits phenotypic
      risk factors for CMM such as red hair and atypical moles.

PMID- 7574833
TI  - Reproducible measurements to quantify cutaneous involvement in scleroderma.
AB  - BACKGROUND AND DESIGN: Because the current assessment of scleroderma through
      clinical skin scoring is subjective and imprecise, we devised fully quantitative
      measures of cutaneous involvement. First, we developed image analysis software
      for calculating the density of dermal collagen from 58 scleroderma and 327
      control biopsy specimens. Second, using a durometer gauge, we obtained
      measurements of skin hardness over 12 body regions for 13 patients with
      scleroderma and 100 controls. We obtained serial durometer measurements at 2-cm
      intervals over the arms of four patients with scleroderma, correlating them with
      blinded assessments of skin score. Third, we produced two-dimensional laser
      Doppler maps of cutaneous blood flow over the dorsal aspect of the hands of 10
      patients with scleroderma and 16 controls and, with software, we determined the
      mean red blood cell flux, density of arteriolar islands, and percentage of
      avascular area at each measured site. RESULTS: Average collagen density was
      significantly higher in patients with scleroderma (88.5% +/- 6.9%) compared with
      that in controls (75% +/- 9.3%) (P < .001). Durometer measurements were
      significantly greater for patients with scleroderma (P < .05) over the finger,
      hand, wrist, forearm, and ventral aspect of the arm. In individual patients, the
      measurements paralleled with skin score. In patients with scleroderma, mean red
      blood cell flux (483.2 +/- 421.2 mV) and arteriolar island density (1.4 +/-
      0.5/cm2) were significantly greater than were the control averages (276.3 +/-
      146.3 mV [P < .03] and 1.0 +/- 0.5/cm2 [P < .013], respectively). CONCLUSIONS:
      Dermal collagen density and durometer measurements of skin hardness accurately
      quantify skin sclerosis in scleroderma and permit the determination of sclerotic
      borders, respectively. Increased cutaneous red blood cell flux and greater use of
      microvascular reserve reflect defects in vascular regulation inherent to the
      disease. These reproducible measurements will allow us to more precisely monitor
      the progression of scleroderma, evaluate its response to experimental treatments,
      and investigate its pathogenetic origins.

PMID- 7574834
TI  - Sclerosis of the skin in the GEMSS syndrome. An overproduction of normal
      collagen.
AB  - BACKGROUND: We describe a recently observed set of autosomal dominant GEMSS
      (glaucoma, lens ectopia, microspherophakia, stiffness of the joints, and
      shortness) syndrome in a 47-year-old woman and her 23-year-old son. In addition,
      sclerosis of the skin, from which both patients suffered, is investigated in
      detail. OBSERVATIONS: The histologic examination of skin biopsy specimens
      obtained from the upper aspects of the backs of both patients revealed a markedly
      thickened dermis. Immunohistochemical examination of the dermal collagen bundles
      showed a collagen pattern similar to systemic sclerosis and normal control skin.
      In situ hybridization showed a markedly enhanced gene expression of transforming
      growth factor beta 1. CONCLUSION: The sclerotic skin changes in GEMSS syndrome
      are the result of an abnormally increased production of normal collagen that
      might be attributable to the enhanced in situ production of transforming growth
      factor beta 1.

PMID- 7574835
TI  - Sweet's syndrome leading to acquired cutis laxa (Marshall's syndrome) in an
      infant with alpha 1-antitrypsin deficiency.
AB  - BACKGROUND: Marshall's syndrome is a rare pediatric skin disease that is
      characterized by acquired, localized neutrophilic dermatitis (Sweet's disease),
      followed by loss of elastic tissue in the dermis and cutis laxa. The cause of
      this syndrome is unknown. alpha 1-Antitrypsin (alpha 1-AT) deficiency is a
      codominantly inherited disorder of alpha 1-AT, the major serum antiprotease
      active against a number of serine-type proteases. OBSERVATIONS: The first patient
      with classic Marshall's syndrome who had coexisting alpha 1-AT deficiency and a
      review of other cases of Marshall's syndrome are presented, and pathogenic
      mechanisms are discussed. CONCLUSIONS: A deficiency of alpha 1-AT may allow
      proteases such as neutrophil elastase to destroy dermal elastin and, thus,
      produce cutis laxa in Marshall's syndrome. Other cases of acquired cutis laxa
      should be screened for alpha 1-AT deficiency to further evaluate this association
      and to enable patients and their families to be counseled about possible systemic
      complications of alpha 1-AT deficiency.

PMID- 7574836
TI  - Cutaneous manifestations of African trypanosomiasis.
AB  - BACKGROUND: Dermatologists may evaluate patients with African trypanosomiasis.
      The currently available dermatologic literature does not review the cutaneous
      manifestations of African trypanosomiasis. OBSERVATION: We describe an American
      man who acquired African trypanosomiasis while hunting in Tanzania, and we review
      and classify the cutaneous findings of this disease. This article reports the
      results of the first biopsy of a trypanid and depicts trypanosomes on the first
      touch preparation done from a trypanid biopsy specimen. Rare color photographs of
      trypanids are shown. CONCLUSIONS: Recognition of the unique cutaneous
      manifestations of African trypanosomiasis may allow dermatologists to make a
      rapid diagnosis that is essential for timely treatment and survival. Classifying
      the disease with primary chancriform, secondary hemolymphatic, and tertiary
      central nervous system stages should improve the understanding of the complex
      natural history of African trypanosomiasis.

PMID- 7574837
TI  - Hepatitis C virus in dermatology. A review.
AB  - BACKGROUND: Hepatitis C virus (HCV) is the main causative agent of parenterally
      transmitted non-A, non-B viral hepatitis, Infections with HCV may be associated
      with disorders of various organs other than the liver, essentially through
      immunologic mechanisms. OBJECTIVES: To provide an update on HCV and to review and
      discuss dermatologic disorders directly or indirectly related to HCV-induced
      liver disease. OBSERVATIONS: The main dermatologic disorders in HCV infection
      include (1) vasculitis (mainly cryoglobulin-associated vasculitis, the cause of
      which is HCV in most cases, and, possibly, some cases of polyarteritis nodosa);
      (2) sporadic porphyria cutanea tarda; (3) cutaneous and/or mucosal lichen planus;
      and (4) salivary gland lesions, characterized by lymphocytic capillaritis,
      sometimes associated with lymphocytic sialadenitis resembling that of Sjogren's
      syndrome. CONCLUSIONS: Hepatitis C virus is the cause of, or is associated with,
      various dermatologic disorders. In patients with such disorders, HCV infection
      must be sought routinely because antiviral therapy may be beneficial in some of
      them.

PMID- 7574838
TI  - Long-standing verrucous lesion. Chromomycosis.

PMID- 7574839
TI  - Enlarging nodules on the toe of an infant. Digital fibrous tumor of childhood.

PMID- 7574840
TI  - Erythematous papules in a patient with rheumatoid arthritis. Rheumatoid
      neutrophilic dermatitis (RND).

PMID- 7574841
TI  - Congenital absence of skin and blistering in a neonate. Bart's syndrome and
      mandibulofacial dysostosis.

PMID- 7574842
TI  - Evidence that sunscreens prevent UV radiation-induced immunosuppression in
      humans. Sunscreens have their day in the sun.

PMID- 7574844
TI  - Is dermatology slipping into its anec-dotage?

PMID- 7574843
TI  - The greed of dermatologists.

PMID- 7574845
TI  - Regression of sclerodermatous skin lesions in a patient with carcinoid syndrome
      treated by octreotide.

PMID- 7574846
TI  - Fetal morbidity in herpes gestationis.

PMID- 7574847
TI  - PUVA-bath photochemotherapy of lichen planus.

PMID- 7574848
TI  - Aggressive squamous cell carcinomas in patients treated with extracorporeal
      photopheresis for cutaneous T-cell lymphoma.

PMID- 7574849
TI  - Toxic epidermal necrolysis in Singapore, 1989 through 1993: incidence and
      antecedent drug exposure.

PMID- 7574850
TI  - Childhood cancers in Zambia before and after the HIV epidemic.
AB  - Human immunodeficiency virus (HIV) related cancers in children are not as common
      and as well described as in adults. An HIV epidemic has been prevalent in Zambia
      since 1983-1984. To study the effect of the epidemic on the epidemiology of
      cancers in children a retrospective study was undertaken at the University
      Teaching Hospital (UTH), Lusaka, Zambia. All the histopathological records from
      1980 to 1992 were reviewed and all cases of cancers in children less than 14
      years of age were analysed. In order to define the effect of the HIV epidemic,
      the epidemiological features of various childhood cancers occurring before
      (during the years 1980-1982) and after (during the years 1990-1992) the onset of
      the HIV epidemic were compared. A significant increase in the occurrence of total
      childhood cancers was found. This is mostly due to a highly significant increase
      in the incidence of paediatric Kaposi's sarcoma (p = 0.000016), which is causally
      related to HIV infection, and a significant increase in the incidence of
      retinoblastoma (p = 0.02), which has an unknown relation to HIV infection. Though
      not yet statistically significant, there has also been a gradual and sustained
      increase in the incidence of non-Hodgkin's lymphoma, nasopharyngeal carcinoma,
      and rhabdomyosarcoma. There has been a significant reduction in the incidence of
      Burkitt's lymphoma. A prospective in depth epidemiological study of HIV related
      childhood cancers in Africa is urgently needed.

PMID- 7574851
TI  - Non-convulsive status epilepticus.
AB  - The clinical, electrographic and reported neuropsychological features of 50
      children with non-convulsive status epilepticus (NCSE) were reviewed and the
      children's progress followed for one to five years. NCSE occurred in a variety of
      epilepsies, especially the Lennox-Gastaut syndrome. Clinical manifestations
      ranged from obvious mental deterioration to subtle changes. The condition had
      often been overlooked or misinterpreted and many children had experienced
      repeated episodes over long periods. Following diagnosis, immediate treatment was
      often not attempted or was not successful. Further episodes of NCSE occurred in
      the majority of children during the follow up period. Failure to recognise NCSE
      and to treat episodes promptly, and the high rate of recurrence, is of particular
      concern in view of fears that repeated exposure to this condition might be brain
      damaging. At least 28 children in the present series showed evidence of
      intellectual or educational deterioration over the period during which NCSE had
      occurred, although the exact cause was difficult to determine.

PMID- 7574852
TI  - Genetic factors in the presence, severity, and triggers of asthma.
AB  - The role of heredity in the presence of asthma, severity of the condition, and
      impact of 12 specific triggers of attacks was investigated. Health surveys
      containing questions about children's asthma characteristics were completed by
      325 families with twin children across the United States. Data for 39 monozygotic
      twin pairs and 55 same sex dizygotic twin pairs who were between 2 and 20 years
      of age and had asthma present in at least one member of each pair were received
      and analysed. Results revealed higher concordance for the presence of asthma
      among monozygotic (58.97%; n = 23) than dizygotic twins (23.64%; n = 13). Further
      analyses were restricted to data from the concordant monozygotic and dizygotic
      twin pairs. Asthma severity (the product of attack frequency and intensity
      ratings) was significantly correlated for monozygotic pairs but not for dizygotic
      pairs, and this difference in monozygotic and dizygotic severity correlations was
      significant. Also, monozygotic twins showed significantly higher correlations
      than dizygotic twins for the impacts of two asthma triggers: respiratory
      infection and physical activity. These results indicate a role of heredity in the
      presence of asthma and suggest that genetic factors may also affect the severity
      of children's asthma condition and the impact of respiratory infection and
      physical exertion as asthma triggers.

PMID- 7574853
TI  - Effect of respiratory virus infections including rhinovirus on clinical status in
      cystic fibrosis.
AB  - One hundred and eight patients with cystic fibrosis were investigated over one
      year to determine whether an association existed between rhinovirus or other
      respiratory virus infection and clinical status. Forced expiratory volume in one
      second (FEV1), forced vital capacity (FVC), Shwachman score, Chrispin-Norman
      chest radiograph score, and percentage weight for height were recorded at the
      beginning and end of the study; days of intravenous antibiotics were noted.
      Nasopharyngeal aspirates were taken for viral studies during respiratory
      exacerbations. Serum was collected at enrollment and 2-6 weeks after each
      respiratory exacerbation. One hundred and fifty seven exacerbations occurred in
      76 patients. Respiratory virus infection was detected in 44 exacerbations and
      rhinovirus was present in 16% (25/157) of exacerbations. Patients with one or
      more respiratory virus infections were compared with those who had none. When all
      respiratory virus infections were considered, patients had a significantly
      greater deterioration in Shwachman score and received significantly more days of
      intravenous antibiotics. When rhinovirus was considered separately, patients
      received significantly more days of intravenous antibiotics, but showed no
      deterioration in clinical status. However, patients infected with another
      respiratory virus had a significant decline in FEV1, with trends towards
      significance for decline in FVC and Shwachman score.

PMID- 7574854
TI  - Role of gastro-oesophageal reflux in infant irritability.
AB  - Gastro-oesophageal reflux (GOR) disease may cause excessive crying in infants.
      The role of GOR was evaluated in infant irritability and an attempt was made to
      define clinical predictors of pathological reflux. Seventy consecutively admitted
      infants with irritability and presumptive GOR were retrospectively reviewed. All
      had undergone prolonged oesophageal pH monitoring. Pathological GOR was defined
      as a fractional reflux time of > or = 10% and was significantly less common in
      infants under 3 months (one of 24; 4.2%) than in older infants (10 of 46; 21.7%).
      All infants with pathological GOR presented with frequent vomiting, and 'silent'
      pathological reflux did not occur. Poor weight gain, feeding refusal,
      backarching, and sleep disturbance were not significantly associated with
      pathological GOR. The results suggest that pathological GOR is an unlikely cause
      of infant irritability under the age of 3 months.

PMID- 7574855
TI  - Fluid intake and industrial processing in apple juice induced chronic non
      specific diarrhoea.
AB  - Dietary factors have been shown to contribute to the occurrence or persistence of
      chronic non-specific diarrhoea (CNSD). Among these are low dietary fat, high
      fluid consumption, and the consumption of apple juice. Prompted by the clinical
      impression that freshly pressed and unprocessed ('cloudy') apple juice was less
      likely to induce diarrhoea than normal, enzymatically processed ('clear') apple
      juice, both juices were compared in terms of carbohydrate malabsorption, gastric
      emptying, and effects on defecation patterns. Clear and cloudy apple juice differ
      in their fibre and non-absorbable monosaccharide and oligosaccharide contents.
      Ten healthy children aged 3.6 to 5.9 years ingested 10 ml/kg of clear and cloudy
      apple juice; in five of them it was enriched with 40 mg of [1-13C]-glycine. Clear
      apple juice resulted in increased (> or = 20 ppm) breath hydrogen excretion in
      8/10, compared with 5/10 after cloudy apple juice; peak breath hydrogen was
      higher in the clear apple juice group (35 (4) and 18 (3) ppm, respectively).
      Gastric emptying as determined by means of labelled breath carbon dioxide (13CO2)
      excretion was similar with both juices. In a four week crossover clinical trial
      12 children, formerly diagnosed as having CNSD, were given extra clear fluids
      (excluding fruit juices; > or = 50% over basal consumption), clear apple juice,
      or cloudy apple juice, for five day periods. Extra fluids and cloudy apple juice
      did not influence stool frequency and consistency compared with the basal period.
      In contrast, clear apple juice significantly promoted diarrhoea. It is suggested
      that, in addition to fructose, the increased availability of non-absorbable
      monosaccharides and oligosaccharides as a result of the enzymatic processing of
      apple pulp is an important aetiological factor in apple juice induced CNSD.

PMID- 7574856
TI  - A double blind, placebo controlled study of the effects of low dose testosterone
      undecanoate on the growth of small for age, prepubertal boys.
AB  - OBJECTIVE: To assess whether very low doses of testosterone can accelerate growth
      without an undue advance in bone age in prepubertal boys with constitutional
      delay of growth. SUBJECTS: 23 prepubertal boys aged 11-14 years with height at or
      below the third centile for chronological age. DESIGN: Randomised, double blind
      trial comparing oral testosterone undecanoate 20 mg once daily versus placebo for
      six months. The 18 months' observation period of each subject comprised a six
      month pretreatment period, followed by a six month treatment (testosterone
      undecanoate or placebo) period, and a six month period after termination of
      treatment. OUTCOME MEASURES: At intervals of six months standing and sitting
      height were measured. Bone age, pubertal stage, weight, and lean body mass were
      also determined. Growth hormone, luteinising hormone, and follicle stimulating
      hormone secretion and testosterone concentration were measured before, after, and
      six months after treatment. RESULTS: Boys taking testosterone undecanoate (n =
      11) showed a significantly greater height velocity (mean (SEM) 5.84 (0.53)
      cm/year) and sitting height velocity (3.54 (0.57) cm/year) during treatment than
      the placebo treated boys (n = 12, height velocity = 3.38 (0.22) cm/year, sitting
      height velocity = 1.58 (0.19) cm/year. There were no significant differences
      between the groups regarding changes in growth hormone, gonadotrophins,
      testosterone, or dihydrotestosterone concentrations. Bone age was not advanced
      significantly more rapidly in either group. CONCLUSIONS: There is accelerated
      gain in height during six months of treatment with low dose testosterone
      undecanoate, without a significantly greater rise in bone age compared with
      controls. Testosterone undecanoate is a safe, well tolerated, and effective
      treatment in the management of constitutional delay of growth.

PMID- 7574857
TI  - Intellectual performance after presymptomatic cranial radiotherapy for leukaemia:
      effects of age and sex.
AB  - Cognitive outcome, as measured by verbal and performance IQs, was compared in 35
      girls and 47 boys who were in first remission for acute lymphoblastic leukaemia.
      All children had received presymptomatic cranial radiotherapy and intrathecal
      methotrexate. The mean age at diagnosis was 4.2 years and the mean elapsed time
      from initial diagnosis to intellectual assessment was 7.1 years. Results showed
      that children irradiated before the age of 4 years were impaired in certain
      aspects of non-verbal ability, as well as in measures of short term memory and
      attention, calculated by factor scores derived from selected subtests of the IQ
      test. Subtests requiring verbal and non-verbal reasoning showed the greatest
      impairment after early diagnosis and treatment. In addition girls were
      selectively impaired in verbal IQ and other aspects of verbal ability, with the
      degree of impairment exacerbated by early treatment. No relationship was found
      between degree of impairment and either time since treatment or number of
      methotrexate injections. It is concluded that early age at irradiation increases
      the risk of impaired intellectual outcome, particularly in girls.

PMID- 7574858
TI  - Growth and puberty after growth hormone treatment after irradiation for brain
      tumours.
AB  - The impact of treatment with either cranial or craniospinal irradiation with or
      without cytotoxic chemotherapy for a brain tumour distant from the hypothalamic
      pituitary axis was assessed in 29 children who had reached final height. All had
      received growth hormone treatment for radiation induced growth hormone
      deficiency. Final height, segmental growth during puberty, and duration of
      puberty were studied. Both craniospinal irradiation and the use of chemotherapy
      resulted in a significant and equal reduction in final height; this effect in
      those children who received both craniospinal irradiation and chemotherapy was
      additive. The degree of height loss was related to the age at irradiation, the
      most profound effect on final height occurring in the youngest at irradiation.
      The mean duration of puberty from G2-G4/B2-B4 (1.97 years) was not significantly
      different from the duration of puberty in normal children. Growth hormone
      increases growth velocity in children with radiation induced growth hormone
      deficiency but their final height is significantly less than their mid-parental
      height. The use of spinal irradiation and chemotherapy in the original treatment
      of brain tumours has a marked effect on growth which is not overcome with the use
      of growth hormone treatment in current doses. Early puberty of normal duration
      contributes to poor growth.

PMID- 7574859
TI  - ECG and echocardiographic diagnosis of pulmonary thromboembolism associated with
      central venous lines.
AB  - The aim was to establish the prevalence of pulmonary embolism in 21 children
      (median age 12 months; range 5-132 months) with central venous lines in situ > 3
      months (median 10 months; range 3-47). Twelve-lead electrocardiograms (ECGs) and
      echocardiograms were analysed in a retrospective study using ECG and
      echocardiographic criteria for pulmonary embolism-previously established and
      validated in adult patients- and standard paediatric ECG values as control data.
      Patients were scored as having definite (n = 7), probable (n = 5), or no
      pulmonary embolism (n = 9). Overall 57% of ECGs showed abnormalities compatible
      with pulmonary embolism. In two patients, serial ECGs obtained during an acute
      cardiorespiratory illness showed cumulative changes diagnostic of pulmonary
      embolism. Eight of 12 patients with abnormal ECGs had echocardiography; in seven
      of these (88%) the right ventricular end diastolic diameter was > 2SD above the
      mean value for age. Twelve of the patients included in this study have died; two
      died following an acute respiratory illness. There was postmortem evidence of
      pulmonary thromboembolism in both of the two children for whom necropsy
      information was available. The data suggest that pulmonary embolism is common in
      children who have central venous lines in situ for > 3 months. Serial studies are
      of value in some patients. Pulmonary embolism may compromise the long term
      survival of children with small bowel failure and preclude consideration for
      liver and small bowel transplantation.

PMID- 7574860
TI  - Foot pathology in insulin dependent diabetes.
AB  - OBJECTIVES: Foot pathology is a major source of morbidity in adults with
      diabetes. The aim of this study was to determine if children with insulin
      dependent diabetes have an increased incidence of foot pathology compared with
      non-diabetic children. DESIGN: Questionnaire, clinical examination, and
      biomechanical assessment. SUBJECTS: 67 diabetic children and a comparison group
      matched for age, sex, and social class. RESULTS: We found significantly more foot
      pathology in the children with diabetes (52 children) than the comparison group
      (28 children); with more biomechanical anomalies (58 children with diabetes, 34
      comparison group); and a higher incidence of abnormal skin conditions (53
      children with diabetes, 27 comparison group). Forty two children with diabetes
      had received foot health education compared with 27 in the comparison group, but
      the study revealed ignorance and misconceptions among the diabetic group, and
      previous contact with a podiatrist was minimal. CONCLUSIONS: The survey suggests
      that children with diabetes have an increased incidence of foot pathology
      justifying greater input of podiatric care in the hope of preventing later
      problems.

PMID- 7574861
TI  - A crossover comparison of extended release felodipine with prolonged action
      nifedipine in hypertension.
AB  - In a crossover design, control of blood pressure by extended release felodipine
      was compared with control by prolonged action nifedipine in 21 children with
      renal hypertension. Compliance with once daily felodipine was higher than with
      nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood
      pressure was lower during the day with felodipine than with nifedipine, at 77.6
      (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the
      percentage of the day during which the child had blood pressure exceeding the
      upper limits of normal for age) was lower for felodipine than for nifedipine:
      43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though
      this did not reach statistical significance. These data suggest that once a day
      felodipine is effective in children with hypertension. This may be because of
      improved compliance.

PMID- 7574862
TI  - Visceral leishmaniasis: rapid response to AmBisome treatment.
AB  - There appears to be an increase in imported cases of visceral leishmaniasis in
      Northern Europe; many are children infected on holiday in the Mediterranean.
      Making the diagnosis in young children can be difficult especially when an
      adequate travel history is not obtained at presentation. Two infants with
      visceral leishmaniasis are presented who were initially felt to have alternative
      diagnoses and who subsequently responded dramatically to a short course of
      liposomal amphotericin B (AmBisome).

PMID- 7574863
TI  - Latex agglutination testing in bacterial meningitis.
AB  - The value of the latex agglutination test in meningitis was assessed. This was
      positive in 60% cases of Streptococcus pneumoniae, 93% of Haemophilus influenzae
      type b, and 39% of Neisseria meningitidis infections. We cannot support the view
      that this test was more valuable than Gram staining in partially treated
      meningitis and cannot recommend its routine use. It may, however, be valuable if
      Gram staining does not identify an organism or if it suggests meningococcal
      infection.

PMID- 7574864
TI  - Reactivation of chickenpox contracted in infancy.
AB  - Varicella zoster virus DNA in mononuclear cells was studied by the polymerase
      chain reaction to obtain virological evidence of reactivation in the children who
      had contracted chickenpox in infancy. The results appear to explain why
      chickenpox in infancy is a risk factor for herpes zoster in immunocompetent
      children.

PMID- 7574865
TI  - Are nappy sterilisers associated with SIDS? New Zealand Cot Death Study Group.
AB  - Chemicals used to clean nappies have been suggested as a cause of sudden infant
      death syndrome (SIDS). Parents of 393 cases and 1592 controls were questioned
      about nappy cleaning procedures. Soaking in sterilisers followed by rinsing in
      water had a relative risk of 0.91 compared with other cleaning procedures. Nappy
      cleaning methods are not related to SIDS.

PMID- 7574866
TI  - Coeliac disease in children of West Indian origin.
AB  - Coeliac disease is uncommon in populations of non-European origin. Two English
      born West Indian children with coeliac disease are presented. The diagnosis
      should be considered in children of West Indian origin with chronic diarrhoea.

PMID- 7574867
TI  - Presenting a scientific paper, including the pitfalls.
AB  - The tone of the presentation is set with the writing of the abstract. Wanting a
      trip to Vienna is not a good enough reason for framing an abstract unless the
      data are really interesting. If you don't find them so, you can bet your life
      that nobody else will. Have you presented the work before? Increasingly, the
      forms inviting abstracts stipulate that they should contain novel data. This
      protects the audience from boredom and your reputation from the aspersion that
      you never have anything new to say. It has been my practice to communicate
      similar data at a second meeting provided it contains some new results and that
      it is targeted at a totally unrelated specialist group. Hopefully, no one will
      have heard the information before. However, it is not acceptable to simply rehash
      the same abstract but should reflect the special interests of the second group.
      If one genuinely wants the abstract accepted for oral presentation it must
      contain a clear hypothesis, a brief description of methods, an exposition of
      results, and a conclusion. That well worn phrase 'results will be presented'
      simply raises the suspicion that the author is hoping that the data will be ready
      by the time that the conference begins. Sometimes, in the rush to meet deadlines
      for abstract submission, the needs of coauthors are overlooked. This is a
      sensitive area and can easily temporarily wreck what appeared to be a harmonious
      collaboration. Do make sure that all coauthors have seen the abstract before
      submission and are happy with the content--it is good research practice and
      important to the smooth running of the research group.

PMID- 7574868
TI  - Short bowel syndrome.

PMID- 7574869
TI  - Making paediatric assessment in suspected sexual abuse a therapeutic experience.

PMID- 7574870
TI  - Statistics from the inside. 15. Multiple regression (1).

PMID- 7574871
TI  - Cellular profile of bronchoalveolar lavage fluid in pulmonary tuberculosis.

PMID- 7574872
TI  - The Family Fund database--an underused research resource.

PMID- 7574873
TI  - Screening for biliary atresia.

PMID- 7574874
TI  - Double blind placebo controlled trial of pizotifen syrup in the treatment of
      abdominal migraine.

PMID- 7574875
TI  - Medicalisation of the normal variant--treatment of the short, sexually immature
      adolescent boy.

PMID- 7574876
TI  - Colonic strictures in cystic fibrosis.

PMID- 7574877
TI  - Minoxidil induced hair growth after leukaemia treatment?

PMID- 7574878
TI  - Management of anaphylactic reactions to food.

PMID- 7574879
TI  - Ectodermal dysplasia and immunodeficiency.

PMID- 7574880
TI  - The classification of disability.

PMID- 7574881
TI  - Investigation of mitochondrial disease.

PMID- 7574882
TI  - Genetic testing of children.

PMID- 7574883
TI  - Dichlone-induced oxidative stress in a model insect species, Spodoptera eridania.
AB  - Southern armyworm, Spodoptera eridania, larvae were provided ad libitum 0.002
      0.25% w/w dichlone, 2,3-dichloro-1,4-naphthoquinone (CNQ). Larval mortality
      occurred in a time-and-dose dependent manner, with an LC17 of 0.01% and an LC50
      of 0.26% CNQ at day-5. Extracts of larvae fed control, 0.01, and 0.25% CNQ diets
      for 5 days were assayed for antioxidant enzymes. While 0.01% CNQ had a mild
      effect, 0.25% CNQ profoundly increased levels of all antioxidant enzymes that
      were examined. The increases as compared to control were: 5.3-, 1.9-, 3.2-, 2.6-,
      2.8-, and 3.5-fold higher for superoxide dismutase, catalase, glutathione
      transferase and its peroxidase activity, glutathione reductase and DT-diaphorase,
      respectively. At 0.01% CNQ, the thiobarbituric acid reactive substances (TBARS)
      were similar to the control group. However, despite the induction from 0.25% CNQ
      of all enzymes examined, the lipid peroxidation was not attenuated; the TBARS
      were 29.7% over the control value. High mortalities and CNQ-induced pathologies
      reflected in retarded growth, wasting syndrome, and diuresis clearly indicated
      that the insect sustained severe oxidant-induced injuries before appropriate
      defenses were fully mobilized. Thus, this quinone causes an oxidative stress in a
      model insect species analogous to that observed in mammalian species.

PMID- 7574884
TI  - Chronic toxicity of fumonisins from Fusarium moniliforme culture material (M
      1325) to mink.
AB  - Adult female mink (Mustela vison) were fed a diet that contained Fusarium
      moniliforme culture material that provided dietary concentrations of 89 ppm
      fumonisin B1, 21 ppm fumonisin B2, and 8 ppm fumonisin B3 for 87 days. During the
      trial, there was mild lethargy in the mink fed fumonisins, but no other clinical
      signs or differences in feed consumption (measured during the first two weeks),
      body weights, or survivability were observed between the fumonisin-treated and
      control mink. Several hematologic parameters (mean corpuscular hemoglobin
      concentration, plasma total solids, and lymphocyte concentration) and serum
      chemical concentrations (globulin, phosphorus, potassium, blood urea nitrogen,
      creatinine, bilirubin, and cholesterol) and activities (alkaline phosphatase,
      alanine aminotransferase, amylase, and aspartate aminotransferase) were greater
      in the mink fed fumonisins than in the controls. Serum albumin/globulin and
      sodium/potassium ratios and chloride concentrations were lower in the fumonisin
      fed mink than in the controls. The concentrations of free sphinganine and the
      ratio of free sphinganine to free sphingosine in the liver and kidneys of the
      fumonisin-treated mink were greater than in the control mink. No histopathologic
      alterations were associated with fumonisin treatment. These results indicate that
      long-term dietary exposure to F. moniliforme culture material containing 118 ppm
      total fumonisins is not lethal to adult mink, but can produce adverse
      physiological effects in the animals.

PMID- 7574885
TI  - Genes and agents: how to prioritize to prevent disease.

PMID- 7574886
TI  - An outbreak of naphthalene di-isocyanate-induced asthma in a plastics factory.
AB  - Seven cases of possible naphthalene di-isocyanate-related occupational asthma
      occurred in 1987 and 1988. These cases were reported to the National Institute
      for Occupational Safety and Health by personnel at a Midwest factory that
      manufactured plastic wheels for fork-lift trucks. The reporting of cases prompted
      (a) an evaluation of the workplace, including a medical screening of workers, to
      detect additional cases; and (b) an industrial-hygiene survey to determine the
      level of exposure to isocyanates.

PMID- 7574887
TI  - Risk factors for occupational illnesses associated with the use of paraquat (1,1'
      dimethyl-4,4'-bipyridylium dichloride) in California.
AB  - This study was conducted to identify risk factors for paraquat-related
      occupational illnesses. Pesticide-related illness is a reportable disease in
      California. A total of 231 skin (26.0%), eye (32.0%), local respiratory (3.5%),
      and systemic (38.5%) paraquat-related cases were reported to the Worker Health
      and Safety Branch, California Department of Food and Agriculture, during 1971
      through 1985. Following paraquat exposure, we found no cases of pulmonary
      fibrosis. Annual numbers of cases ranged between 1 and 33 (median = 14 cases/y).
      Information on illnesses reported during 1981 through 1985 (n = 62) was merged
      with detailed information on paraquat use in agricultural settings (111,716
      applications) for the same years. We found that crop treated, method of
      application, and season of application all contributed independently to the risk
      of reported illness. Hand application was associated with a higher risk of
      illness, compared with air application (RR = 99.1, 95% CI = 22.16-443.47); summer
      application was associated with a higher risk of illness than was winter
      application (RR = 4.1, 95% CI = 1.91-8.61); and fruit trees were associated with
      higher risk of illness than were other crops (mainly cotton) (RR = 3.6, 95% CI =
      1.18-11.21).

PMID- 7574888
TI  - Peripheral neurologic abnormalities among roofing workers: sentinel case and
      clinical screening.
AB  - Peripheral neuropathy developed in a 52-y-old roofer who was exposed to multiple
      solvents in one-ply roofing systems. Forty roofers who were exposed to various
      roofing systems were assessed by symptoms, occupational history, standardized
      physical examination, and measurement of vibrotactile thresholds of the upper and
      lower extremities. After exclusion of roofers who were predisposed to peripheral
      neuropathy, we detected abnormal vibrotactile thresholds in 42% (p < .001) of
      roofers' dominant toes and in 36% (p < .001) of roofers' nondominant toes; fewer
      roofers had abnormal sensory physical examinations or reported neuritic symptoms.
      Roofing workers may be at increased risk of peripheral neuropathy, perhaps
      resulting from exposure to solvents--particularly n-hexane, associated with one
      ply roofing systems.

PMID- 7574889
TI  - Clinical application of in vivo tibial K-XRF for monitoring lead stores.
AB  - We used in vivo tibial K-x-ray fluorescence for clinical evaluation of bone lead
      stores in 31 patients suspected of excessive lead absorption. Four clinical
      situations were examined: (1) postchelation therapy, (2) renal failure, (3) home
      exposure, and (4) occupational exposure. K-x-ray fluorescence assisted in
      determining the magnitude of body lead stores in patients with known excessive
      lead exposure. Serial measurements revealed a reduction in bone lead that
      occurred over the years, during which there was an absence of continued exposure;
      this reduction occurred more rapidly during chelation therapy. Sustained high
      bone lead levels following chelation therapy in two children were consistent with
      elevated lead stores from prior pica. In a patient with renal failure, K-x-ray
      fluorescence demonstrated massive lead stores at a time when chelation testing
      was not possible. In other cases, bone lead levels indicated the possible
      contribution of lead nephropathy to renal diseases of other etiologies. In
      individuals exposed to lead during home renovations, K-x-ray fluorescence
      provided reassurance that past exposure did not result in elevated body lead
      stores decades later. In the occupational setting, K-x-ray fluorescence
      documented cumulative lead stores in workers whose exposures varied in intensity
      and duration. The examples discussed here show how physicians can use K-x-ray
      fluorescence to deal with practical questions of patient management. As the test
      becomes more generally available, its safety, specificity, and simplicity should
      make it an important alternative to cumbersome chelation tests and potentially
      misleading blood lead measurements.

PMID- 7574890
TI  - Blood lead levels in 2- to 3-year-old children in the Greater Bilbao Area (Basque
      Country, Spain): relation to dust and water lead levels.
AB  - The objectives of this study were to determine blood lead levels in 2-y-old
      children in the Greater Bilbao Area (Basque Country, Spain) and to compare those
      levels with the lead content of different media (i.e., house dust, park dust and
      soil, and water) in the child's environment. Between May and September of 1992,
      138 children, aged 2 to 3 y, were studied. All children were attended by
      pediatricians within the public health-care network, and their parents
      volunteered for the study. A venous blood sample was drawn from each child and
      was analyzed for lead level, and the parents answered a questionnaire that
      addressed the socioeconomic background and habits of the children. The
      environment was investigated in 42 cases. Blood lead levels exceeded 15
      micrograms/dl in 2% of the children, and 14% of the children had levels that
      exceeded 10 micrograms/dl (geometric mean = 5.7 micrograms/dl [4.7-6.7
      micrograms/dl]. Blood lead levels were higher among (a) children whose mothers
      worked outside the home, (b) children whose fathers had only a primary-level
      education, and (c) children who lived in houses constructed prior to 1950. The
      geometrical averages of lead in house dust, park soil, and park dust were 595,
      299, and 136 micrograms/g, respectively. Statistically significant linear
      correlation was found between blood lead level and lead content in park dust, a
      finding that explained a 9% variation in blood lead level; a subgroup of these
      children was also found to have a strong linear association between blood lead
      and lead content in house dust.

PMID- 7574891
TI  - High hair and urinary mercury levels of fish eaters in the nonpolluted
      environment of Papua New Guinea.
AB  - Hair and mercury concentrations of 134 fish-eating subjects in the Lake Murray
      area and 13 non-fish-eating subjects in the upper-Strickland area, Papua New
      Guinea, were studied. Hair mercury levels among the subjects in the Lake Murray
      area (mean = 21.9 micrograms/g, range = 3.7-71.9 micrograms/g) and urinary
      mercury levels (mean = 7.6 micrograms/g creatinine, range = 1.4-25.6 micrograms/g
      creatinine) were markedly higher than levels found in subjects from the upper
      Strickland area (mean hair mercury = 0.75 micrograms/g, mean urinary mercury =
      0.48 micrograms/g creatinine). Mercury intake of the fish eaters, estimated from
      mercury concentrations found in fish and from the observed amounts of fish
      consumed, was approximately 73 micrograms/d. Hair and urinary mercury
      concentrations were correlated significantly (r = .59), indicating that urinary
      mercury excretion was elevated because fish consumption was very high.

PMID- 7574892
TI  - Distribution of selenium and molybdenum and cancer mortality in Niigata, Japan.
AB  - Selenium and molybdenum have inhibitory effects on gastrointestinal
      carcinogenesis. We investigated the levels of selenium and molybdenum in
      sediments and mortality from cancers at specific sites in 19 areas of Niigata
      Prefecture, Japan, and compared these factors. The average concentrations of
      selenium and molybdenum were 0.44 +/- 0.19 ppm (micrograms/g dry weight; mean +/-
      standard deviation) and 3.82 +/- 1.03 ppm, respectively. Selenium was not
      associated significantly with cancer mortality. There were inverse correlations
      between molybdenum levels and female mortality from cancers of the esophagus (r =
      -.446, .05 < p < .1) and rectum (r = -.529, p < .05). Molybdenum was correlated
      positively with female mortality from cancer of the pancreas (r = .603, p < .01).
      Further investigations are needed for causal interpretation of these results.

PMID- 7574893
TI  - Inverse relationship between tobacco smoking and both psychotechnic and education
      levels.
AB  - The relationship between psychotechnic and education levels and smoking habits
      was evaluated in a population of 2,430 Belgian male army conscripts who were 18
      29 y of age. Smoking habits were quantified by a questionnaire and by urinary
      cotinine-to-creatinine concentration ratio. The results were analyzed relative to
      education level (graded 1-4) and to results of psychotechnic tests (scored 1-9).
      The urinary cotinine-to-creatinine concentration ratio was correlated strongly
      with the number of cigarettes smoked/d (r = .76, p < .00005). The concentrations
      averaged 27 +/- 153 ng/mg (mean +/- standard deviation) creatinine in nonsmokers,
      69 +/- 186 ng/mg creatinine in exsmokers, and 388 +/- 392 and 867 +/- 833 ng/mg
      creatinine in subjects who smoked fewer than or more than 10 cigarettes/d,
      respectively. Significant inverse relationships were observed between the urinary
      cotinine-to-creatinine concentration ratio and both education (p < .0001) and
      psychotechnic levels (p < .0001). The inverse relationship between smoking and
      both the education and psychotechnic levels underlined the importance of adapting
      smoking prevention programs to the intellectual capacities of the populations
      targeted.

PMID- 7574894
TI  - Green tobacco sickness: occupational nicotine poisoning in tobacco workers.
AB  - In this study the authors describe the investigation of a 1992 outbreak of green
      tobacco sickness, a form of nicotine poisoning from dermal exposure, among 47
      tobacco workers in a five-county region of central and south-central Kentucky.
      Cases were identified through medical record searches at participating hospitals,
      as well as from reports submitted to the Occupational Health Nurses in
      Agricultural Communities program. A case-control study was undertaken to assess
      risk factors for green tobacco sickness. In a 20-min telephone interview, 40
      cases and 83 controls responded to questions contained in a questionnaire. In
      1992, 47 persons (3 were under age 16 y) in the study region sought medical
      treatment for green tobacco sickness. Twelve persons were hospitalized and 2
      required intensive-care treatment. The crude incidence in 1992 was 10.0/1,000
      tobacco workers. In 1993, 66 cases (7 were under age 16 y) of green tobacco
      sickness were identified in the study region (i.e., annual incidence of
      14.0/1,000). A case-control study demonstrated that ill workers were younger, and
      were more likely to have worked in wet conditions, compared with workers who were
      not ill. Green tobacco sickness is a common problem among tobacco workers that
      may be prevented by avoiding work in wet tobacco or by use of protective
      clothing. Children younger than 16 y of age represented 9% of the green tobacco
      sickness cases in 1992 and 1993. Current occupational safety and health laws do
      not address protection of tobacco workers with respect to green tobacco sickness.

PMID- 7574895
TI  - Lead poisoning in an oil-pipeline maintenance worker.

PMID- 7574896
TI  - Neuropsychiatric sequelae following chemical exposure.

PMID- 7574897
TI  - Growing up exposed: adult manifestations of protracted childhood insecticide
      exposure.

PMID- 7574898
TI  - Neurotoxic impairment in a case of methylethyl-ketone exposure.

PMID- 7574899
TI  - Childhood lead intoxication associated with manufacture of roof tiles and
      ceramics in the Ecuadorian Andes.

PMID- 7574900
TI  - Occurrence and clinical significance of thermophilic actinomycetes in cane-sugar
      mills.

PMID- 7574901
TI  - Illness due to methyl tertiary butyl ether.

PMID- 7574902
TI  - Urinary excretion of cyclophosphamide.

PMID- 7574903
TI  - The effect of preconceptional multivitamin supplementation on the menstrual
      cycle.
AB  - The database of the Hungarian randomised controlled trial of periconceptional
      multivitamin supplementation for the prevention of neural-tube defects was used
      to evaluate the length of the pre- and postovulatory phases of the menstrual
      cycle before and during multivitamin supplementation. The female cycle was more
      regular (i.e., the variance was lower) during the multivitamin supplementation.

PMID- 7574904
TI  - IL-6 and G-CSF levels in amniotic fluid during the second trimester in normal and
      abnormal pregnancies.
AB  - Activity levels of cytokines were measured by stimulation of the cell lines NFS
      60, 7TD1, and TF-1. In 39 samples of amniotic fluid, levels of Granulocyte
      Stimulating Factor (G-CSF) were 1434 +/- 2063 (mean +/- SD) and of Interleukin
      (IL-6) 546 +/- 1071 pg/ml; Granulocyte-Macrophage Colony Stimulating Factor (GM
      CSF) was not detectable. IL-6 was correlated to G-CSF (r = 0.3; p = 0.003). G-CSF
      (p = 0.0002) and IL-6 (p = 0.006) were influenced by Alpha-Fetoprotein (AFP) and
      G-CSF by rhesus-incompatibility (p = 0.0004). These findings suggest that
      cytokines such as IL-6 and G-CSF play some role in physiological and pathological
      pregnancy.

PMID- 7574905
TI  - Smoking, alcohol, sexual behaviour and drug use in women with cervical human
      papillomavirus infection.
AB  - OBJECTIVE: The aim of the study was to determine if smoking is associated with
      cervical human papillomavirus infection (CHPI) independent of sexual risk
      factors. SETTING: Two family planning clinics and one youth clinic in Sweden.
      SUBJECTS: Human papillomavirus (HPV) DNA was found in cervical samples of 66
      (6.8%) of 972 women attending for contraceptive advice, using Southern blot
      tests. RESULTS: Among women with cervical human papillomavirus infection (CHPI),
      33 (50%) were smokers, as compared to 307 (33.9%) among a comparison group of HPV
      negative women (odds ratio = 2.0, 95% CI = 1.2-3.2). After stepwise adjustment
      for number of lifetime partners, number of partners last six months, age at first
      intercourse, alcohol use, drug abuse and history of or current sexually
      transmitted disease other than CHPI, the odds ratio decreased to 1.4 (95% CI =
      0.8-2.4). Recent use of alcohol and ever use of narcotics were also significantly
      correlated to CHPI in crude analyses, but vanished in multifactorial analyses
      after adjustment for the mentioned sexual risk behavioral factors. CONCLUSIONS:
      The results of this study indicate that smoking, alcohol and drug abuse are risk
      markers, but not causal factors, for CHPI.

PMID- 7574906
TI  - P53 protein in 204 patients with primary breast carcinoma--immunohistochemical
      detection and clinical value as a prognostic factor.
AB  - In a retrospective study, 204 formalin-fixed and paraffin-embedded biopsies of
      primary breast carcinomas were tested immunohistochemically for the expression of
      p53 protein (PAb 1801). 38% of the carcinomas were positive with respect to p53.
      The expression of p53 correlated significantly with the loss of tumor
      differentiation (P = 0.013), but not with menopausal status, patients' age, tumor
      size, axillary lymph node involvement or hormone receptor status. The influence
      of p53 expression on prognosis was evaluated in 197 patients (T1-4 N0-2 M0,
      median observation time 72 months). Detection of p53 protein was associated with
      a significantly longer disease-free survival in node-positive women (P = 0.03).
      However, p53 protein did not prove to be a prognostic factor in node-negative
      patients. The results demonstrate the prognostic value of p53 expression in
      breast cancer which appears to be limited to patients with node-positive tumors.

PMID- 7574907
TI  - CD 44 exon v6 as a predictor of lymphatic metastases in cervical carcinoma--an
      immunocytochemical study of 94 cases.
AB  - The relation between expression of several splicing variants of the CD 44
      glycoprotein by tumor cells and the increased risk of metastases was discussed
      recently. By means of an immunocytochemical study (imprint cytology specimens
      from 94 invasive cervical carcinomas) we have shown a significant correlation
      between expression of CD 44 v6 and invasion of lymphatic vessels, lymphangiosis
      carcinomatosa in the primary tumor and the total number of positive pelvic lymph
      nodes. Expression of CD 44 v6 was not correlated with staging, grading and
      histological type. CD 44 v6 could therefore be considered as a predictor of
      lymphatic metastases in cervical carcinoma.

PMID- 7574908
TI  - Color flow mapping of the middle cerebral artery in 23 hydrocephalic fetuses.
AB  - Color flow mapping was performed on 23 fetuses with hydrocephaly. The
      measurements on the middle cerebral artery posed no problem. We found end
      diastolic frequencies in all cases. The pulsatility-indices were raised in only 4
      cases. Color Doppler sonography gave no extra information about diagnosis or
      prognosis.

PMID- 7574909
TI  - Oligohydramnios, intrauterine growth retardation and fetal death due to umbilical
      cord torsion.
AB  - Intrauterine fetal death was observed in a woman at 35 gestational weeks shortly
      after she was admitted to hospital due to suspected placental insufficiency
      expressed by oligohydramnios and fetal growth retardation. The pathologic
      examination showed umbilical cord torsion and an organized thrombus at the site
      of the torsion. This findings could imply that both the fetal death and the
      placental insufficiency were the results of the cord torsion.

PMID- 7574910
TI  - Successful conservative treatment of catamenial pneumothorax with GnRH agonist.
AB  - A thirty four year old woman with recurrent catamenial pneumothorax is described.
      Pleural endometriosis was suspected and cytologic examination of fluid drained
      from the right pleural cavity showed glandular cell clusters of probable
      endometrial origin. The patient received a long-acting GnRH agonist (Triptorelin
      Arvekap-Ipsen) 3.75 mg/month I.M. for nine months and remains asymptomatic with
      regular periods 12 months after discontinuing the treatment.

PMID- 7574911
TI  - [Classification of ovarian tumors based on embryogenesis].
AB  - This paper studies gonadal differentiation into the ovary from the earliest
      interaction between germ cells and somatic cells in the developing urogenital
      ridge up to the formation of primordial follicles. Granulosa cells appear to be
      derived from the breaking down of the cordlike arrangement of epithelial cells
      resulting from proliferation of surface coelomic mesothelium. Thecal cells arise
      from mesenchymal progenitors cells in the ovarian stroma. Based on the findings
      of embryology and biology, the authors then propose a classification of ovarian
      tumors by rearranging the WHO classification.

PMID- 7574912
TI  - [Colonic Histoplasma capsulatum pseudotumor in AIDS. Morphological and
      immunohistochemical diagnosis of an isolated lesion].
AB  - The authors report a case of a 35-year-old man with acquired immunodeficiency
      syndrome (AIDS) and a left colonic mass with Histoplasma capsulatum (H.
      capsulatum). The look-up performed looking for disseminated infection was
      negative. In the absence of positive cultures, the diagnosis was determined
      morphologically based on the presence of yeast observed by light and electron
      microscopy. The diagnosis was also verified by positive immunofluorescence using
      specific anti-Histoplasma antibodies. Gastrointestinal histoplasmosis is a
      frequent complication of AIDS, particularly in some endemic areas of America.
      Association with a disseminated mycotic infection is then common. Histoplasmosis
      is less frequently diagnosed in Europe and isolated involvement of the colon is
      exceptional. When the mycological study is not performed or is negative, only
      morphological and immunohistochemical methods are able to establish the diagnosis
      and eliminate other mycotic diseases occurring during AIDS.

PMID- 7574913
TI  - [Computer-assisted rescreening of cervicovaginal smears stained by the
      Papanicolaou method. Evaluation of the PAPNET system apropos of 225 cases].
AB  - The risk of false-negative smears is currently the main criticism of conventional
      cytological diagnosis of cervical cancer. None of the palliative methods
      (rescreening of a certain number of smears, external and internal laboratory
      controls, screener's training, European recommendations for Quality Assurance
      ...) are completely accurate. This explains the attempt to use automated
      screening of smears. The PAPNET screening system which allows recognition of
      possibly abnormal smears appears to be sufficiently effective. In this study, the
      authors report their personal experience based on a series of 225 cases.
      Moreover, when used wisely, this system may represent a useful teaching tool as
      well as a means of cytopathology Quality Assurance.

PMID- 7574914
TI  - [Quality assurance in anatomo-cytopathology. Cancer of the cervix. Report of a
      study group].

PMID- 7574915
TI  - Subcutaneous sacrococcygeal myxopapillary ependymoma. A case report.
AB  - A case of myxopapillary ependymoma presenting as a primary tumor of the
      subcutaneous tissue of the sacrococcygeal area is reported. The tumor usually
      presents as an asymptomatic mass at the base of the spine in young individuals
      and may therefore be mistaken for a pilonidal cyst. The clinical and pathological
      features of this tumor are discussed.

PMID- 7574916
TI  - [Spinal melanocytic schwannoma with malignant course. Microscopic and
      ultrastructural study of a case].
AB  - The authors report a case of recurrent pigmented intraspinal schwannoma with
      malignant progression. Electron-microscopic study confirmed that melanin pigment
      was produced by tumor cells and that these cells were derived from the nerve
      sheath. The histogenesis of pigmented tumors is explained by their neural crest
      origin and the problem of differential diagnosis of the malignant form with
      melanoma is discussed.

PMID- 7574917
TI  - Well differentiated neuroendocrine carcinoma of the breast. A case report.
AB  - A neuroendocrine breast carcinoma occurring in a 79 year-old woman is presented.
      The case presented typically as a single nodule in the upper and outer quadrant
      of her right breast and showed a pure histology consisting exclusively of
      organoid nests of well differentiated cells that mimicked those of carcinoid
      tumors of the lung. The literature is briefly reviewed and commented. In the
      light of this review, we conclude that the issue of carcinomas with
      neuroendocrine differentiation in breast pathology is controversial and its
      terminology somewhat debatable.

PMID- 7574918
TI  - [Submandibular lymph node metastasis from a subcutaneous neuroendocrine carcinoma
      of the buttock].

PMID- 7574919
TI  - [Constitution of the normal and pathological extracellular matrix].

PMID- 7574920
TI  - [Regulation of the formation of the extracellular matrix].

PMID- 7574921
TI  - [Fibrosis and inflammation].

PMID- 7574922
TI  - [Fibroses: etiologies, characteristics, consequences on the structure and the
      function of organs].

PMID- 7574923
TI  - Detection of occult bone marrow micrometastases in patients with operable lung
      carcinoma.
AB  - OBJECTIVES: A large proportion of patients with operable lung carcinoma (no
      evidence of systemic spread of tumor) develop metastatic disease after primary
      therapy. More sensitive and specific methods are needed to identify patients at
      highest risk for recurrence who may benefit most from adjuvant therapy, while
      sparing those patients who do not require such treatment. SUMMARY BACKGROUND
      DATA: Using epithelial-specific monoclonal antibodies, the authors have developed
      an immunocytochemical assay capable of detecting as few as 2 lung cancer cells in
      1 million bone marrow cells. METHODS: The assay was used to test the bone marrow
      (from resected ribs) of 43 patients with primary non-small cell lung carcinoma
      who showed no clinical or pathologic evidence of systemic disease. RESULTS:
      Occult bone marrow micrometastases (BMMs) were detected in 40% of patients
      (17/43) with non-small cell lung cancer, including 29% (5/17) of patients with
      stage I or II disease and 46% of whom (12/26) had stage III disease. The median
      follow-up was 13.6 months. Patients with occult BMMs had significantly shorter
      times to disease recurrence compared with patients without BMMs (7.3 vs. > 35.1
      months, p = 0.0009). Furthermore, for patients with stage I or II disease, the
      presence of occult BMMs was significantly associated with a higher rate of
      recurrence (p = 0.0004). CONCLUSIONS: The detection of occult BMMs identifies
      patients with operable non-small cell lung carcinoma who are at significantly
      increased risk for recurrence, independent of tumor stage, and may be useful in
      evaluating patients for adjuvant treatment protocols.

PMID- 7574924
TI  - Pancreatic or liver resection for malignancy is safe and effective for the
      elderly.
AB  - BACKGROUND: Liver resection, or pancreaticoduodenectomy, has traditionally been
      thought to have a high morbidity and mortality rate among the elderly. Recent
      improvements in surgical and anesthetic techniques, an increasing number of
      elderly patients, and an increasing need to justify use of limited health care
      resources prompted an assessment of recent surgical outcomes. METHODS: Five
      hundred seventy-seven liver resections (July 1985-July 1994) performed for
      metastatic colorectal cancer and 488 pancreatic resections (October 1983-July
      1994) performed for pancreatic malignancies were identified in departmental data
      bases. Outcomes of patients younger than age 70 years were compared with those of
      patients age 70 years or older. RESULTS: Liver resection for 128 patients age 70
      years or older resulted in a 4% perioperative mortality rate and a 42%
      complication rate. Median hospital stay was 13 days, and 8% of the patients
      required admission to the intensive care unit (ICU). Median survival was 40
      months, and the 5-year survival rate was 35%. No differences were found between
      results for the elderly and those for younger patients who had undergone liver
      resection, except for a minimally shorter hospital stay for the younger patients
      (median, 12 days vs. 13 days; p = 0.003). Pancreatic resection for 138 elderly
      patients resulted in a mortality rate of 6% and a complication rate of 45%.
      Median stay was 20 days, and 19% of the patients required ICU admission, results
      identical to those for the younger cohort. Long-term survival was poorer for the
      elderly patients, with a 5-year survival rate of 21% compared with 29% for the
      younger cohort (p = 0.03). CONCLUSIONS: Major liver or pancreatic resections can
      be performed for the elderly with acceptable morbidity and mortality rates and
      possible long-term survival. Chronological age alone is not a contraindication to
      liver or pancreatic resection for malignancy.

PMID- 7574925
TI  - Long-term results of in situ saphenous vein bypass. Analysis of 2058 cases.
AB  - OBJECTIVE: The authors evaluated the long-term patency and outcome of patients
      undergoing infrainguinal reconstruction using the in situ saphenous vein. SUMMARY
      BACKGROUND DATA: The in situ saphenous vein bypass has demonstrated excellent
      patency and limb salvage rates in numerous studies. The authors previously
      reported their early results with these bypass procedures, and this article
      represents their long-term experience with 2058 in situ saphenous vein bypasses
      during a 20-year period. This comprises the largest series with long-term follow
      up of in situ saphenous vein bypasses in the literature. METHODS: From 1975 to
      1995, 3148 autogenous vein bypasses were performed at the authors' institution,
      of which 2058 used the saphenous vein in situ. The indication for operation was
      limb-threatening ischemia in 1875 of 2058 patients (91%). In 88% of patients with
      an intact ipsilateral saphenous vein, an in situ bypass was completed
      successfully. One thousand twenty-three bypasses (69%) were terminated at the
      infrapopliteal level. Of these bypasses, 1562 of 2058 (76%) were completed using
      the closed in situ technique. RESULTS: The 30-day patency rate was 96%, and the
      cumulative secondary patency was 91%, 81%, and 70% at 1, 5, and 10 years,
      respectively. Limb salvage rates using the in situ bypass were 97%, 95%, and 90%
      at 1, 5, and 10 years, respectively. CONCLUSION: The infrainguinal inflow source,
      length of bypass, specific outflow vessel, or vein diameter did not have a
      significant effect on immediate or long-term bypass performance. These data
      suggest that the in situ saphenous vein is an excellent conduit for
      femoropopliteal and femoral to infrageniculate bypasses for limb salvage.

PMID- 7574926
TI  - Initial experience with transluminally placed endovascular grafts for the
      treatment of complex vascular lesions.
AB  - OBJECTIVES: Complex arterial occlusive, traumatic, and aneurysmal lesions may be
      difficult or impossible to treat successfully by standard surgical techniques
      when severe medical or surgical comorbidities exist. The authors describe a
      single center's experience over a 2 1/2-year period with 96 endovascular graft
      procedures performed to treat 100 arterial lesions in 92 patients. PATIENTS AND
      METHODS: Thirty-three patients had 36 large aortic and/or peripheral artery
      aneurysms, 48 had 53 multilevel limb-threatening aortoiliac and/or
      femoropopliteal occlusive lesions, and 11 had traumatic arterial injuries (false
      aneurysms and arteriovenous fistulas). Endovascular grafts were placed through
      remote arteriotomies under local (16[17%]), epidural (42[43%]), or general
      (38[40%]) anesthesia. RESULTS: Technical and clinical successes were achieved in
      91% of the patients with aneurysms, 91% with occlusive lesions, and 100% with
      traumatic arterial lesions. These patients and grafts have been followed from 1
      to 30 months (mean, 13 months). The primary and secondary patency rates at 18
      months for aortoiliac occlusions were 77% and 95%, respectively. The 18-month
      limb salvage rate was 98%. Immediately after aortic aneurysm exclusion, a total
      of 6 (33%) perigraft channels were detected; 3 of these closed within 8 weeks.
      Endovascular stented graft procedures were associated with a 10% major and a 14%
      minor complication rate. The overall 30-day mortality rate for this entire series
      was 6%. CONCLUSIONS: This initial experience with endovascular graft repair of
      complex arterial lesions justifies further use and careful evaluation of this
      technique for major arterial reconstruction.

PMID- 7574927
TI  - Is the timing of fracture fixation important for the patient with multiple
      trauma?
AB  - OBJECTIVE: The effect of timing of femur fracture fixation for patients with
      multiple trauma was studied to determine the effect of operative timing on
      eventual outcome. METHODS: The relationship between timing of intramedullary rod
      (IMR) placement, degree of injury, and pulmonary complications was studied in 424
      consecutive patients. The authors focused on 105 patients undergoing IMR
      placement with an Injury Severity score (ISS) of greater than or equal to 18. The
      effects of timing of IMR placement on various pulmonary complications, organ
      failure, intensive care unit (ICU) admission, and ventilatory assistance were
      studied for various time intervals. RESULTS: Of the 424 patients, pulmonary
      complications increased slightly in the more seriously injured group (ISS > 18)
      but were not influenced by the timing of IMR placement. Of the 105 patients
      undergoing IMR placement with an ISS > or = 18, only 2 patients died. Both
      patients had an IMR placed in less than 24 hours and died later of head injury
      and delayed hemorrhage. The incidence of organ failure, number of ventilator
      days, and length of ICU stay did not differ between the groups based on timing of
      fracture fixation. The incidence of severe head injuries was higher in the group
      undergoing delayed IMR placement (> 48 hours). CONCLUSIONS: Modest delays in IMR
      placement did not adversely affect patient outcome. Pulmonary complications were
      related to the severity of injury rather than to timing of fracture fixation. In
      a well-integrated trauma system, clinical judgment regarding the timing of IMR
      placement was the most important determinant of outcome. Delays that were made to
      stabilize the patient, treat associated injuries, and plan orthopedic
      reconstruction did not adversely affect patient outcome.

PMID- 7574928
TI  - Major injury leads to predominance of the T helper-2 lymphocyte phenotype and
      diminished interleukin-12 production associated with decreased resistance to
      infection.
AB  - OBJECTIVE: Patients with serious traumatic injury and major burns and an animal
      model of burn injury were studied to determine the effect of injury on the
      production of cytokines typical of the T helper-2 lymphocyte phenotype as opposed
      to the T helper-1 phenotype and on the production of interleukin-12. SUMMARY
      BACKGROUND DATA: Perturbations of natural and adoptive immunity are related to
      the increased susceptibility to infection manifested by seriously injured and
      burn patients. Earlier work has shown that impaired adoptive immunity after
      injury is characterized by diminished production of interleukin-2 (IL-2), a
      product of Th lymphocytes. Exposure of naive Th cells to certain antigens and
      cytokines causes conversion to either the Th-1 or the Th-2 phenotype. Th-1 cells
      produce IL-2 and interferon-gamma (IFN-tau) and initiate cellular immunity. Th-2
      cells secrete interleukin-4 (IL-4) and interleukin-10 (IL-10) and stimulate
      production of certain antibodies. Conversion to the Th-1 phenotype is facilitated
      by IL-12, and conversion to the Th-2 phenotype is promoted by IL-4. The authors
      believed that serious injury might cause conversion of Th cells to the Th-2 as
      opposed to the Th-1 phenotype rather than generalized Th suppression. METHODS:
      The authors studied circulating peripheral blood mononuclear cells (PBMC) from 16
      major burn and 8 trauma patients on 32 occasions early after injury and from 13
      age- and sex-matched healthy individuals for cytokine production after
      phytohemagglutinin stimulation. Also studied was a mouse model of 20% burn injury
      known to mimic the immune abnormalities seen in humans with burns. Splenocytes
      from burn mice, 10 to 12 per group, were studied after activation by concanavalin
      A or by the bacterial antigen Staphylococcus aureus Cowan strain I for cytokine
      production and cytokine messenger RNA expression as determined by reverse
      transcriptase polymerase chain reaction. Burn mice were compared with sham-burn
      controls and attention was focused on day 10 after burn injury, a time when IL-2
      production and resistance to infection are highly suppressed. Finally, burn and
      sham-burn animals, 20 per group, were treated in vivo with IL-12 (25 ng daily for
      5 days) and observed for mortality after septic challenge (cecal ligation and
      puncture [CLP]) performed on day 10 after injury. RESULTS: Peripheral blood
      mononuclear cells from burn and trauma patients produced less IFN-tau, the index
      cytokine of Th-1 cells, than PBMCs from healthy individuals 1 to 14 days after
      burn injury (SE = 77.6 +/- 16 pg/mL patients vs. 141.3 +/- 35 pg/mL controls, p <
      0.05). However, production of IL-4, the index cytokine of Th-2 cells, by patient
      PBMCs was increased (51.0 +/- 13.0 pg/mL patients vs. 26.9 +/- 2.5 controls, p <
      0.05). Splenocytes from mice 10 days after burn injury, when compared with sham
      burn controls, showed diminished production of IL-2 (1.04 +/- 0.91 units/mL burns
      vs. 5.8 +/- 0.55 units/mL controls, p < 0.05) and IFN-tau (1.05 +/- 0.7 units/mL
      burns vs. 12.0 +/- 8.9 units/mL controls, p < 0.05). However, burn splenocytes
      produced more IL-4 (2492 +/- 157.0 pg/mL burns vs. 672.0 +/- 22.7 pg/mL controls,
      p < 0.01) and IL-10 (695.2 +/- 20.8 pg/mL burns vs. 567.0 +/- 16.7 pg/mL
      controls, p < 0.05). Splenocyte production of IL-12 was also reduced after burn
      (0.20 +/- 0.035 units/mL) as compared with sham burn (0.46 +/- 0.08 units/mL, p <
      0.05). The reduction in IL-2, IFN-tau, and IL-12 production by burn splenocytes
      was reflected by a tenfold decrease in expression of their respective cytokine
      mRNAs. In vivo IL-12 treatment of burn animals decreased mortality from CLP on
      day 10 after injury from 85% to 15% (sham-burn mortality after CLP, 15%, p <
      0.05) and increased splenocyte IFN-tau production to supranormal levels.
      CONCLUSIONS: Serious injury induced diminished production of IL-1 2 and a shift
      to the Th-2 phenotype with increased production of IL-4 and IL-10, cytokines
      known to inhibit Th-1 function. The ability of exogenous IL-12 to restore Th-1
      cytokine production and resistance to infection suggests a therapeutic role for
      IL-12 in the immune dysfunction seen after major injury.

PMID- 7574930
TI  - Intestinal radioprotection by vitamin E (alpha-tocopherol).
AB  - OBJECTIVES: The major objective of this study was to test vitamin E as a
      potential radioprotectant for the small bowel of the rat. SUMMARY BACKGROUND
      DATA: Vitamin E has previously been shown to provide radioprotection in animal
      models: increased survival after whole-body irradiation, diminished absorptive
      malfunction, and modest diminution in postirradiation hemolysis. The lumenal
      route for intestinal radioprotection has not been tested. METHODS: Rat mid-small
      bowel was surgically exteriorized and segmented by ties into compartments, each
      of which was filled with a test solution 30 minutes before 1100 cGy of x
      irradiation was administered. After the rats were killed 5 days later, the
      various segments were evaluated for surviving crypts, mucosal height, and goblet
      cell preservation. Lumenal agents included alpha-tocopherol phosphate and alpha
      tocopherol acetate. In a separate study, dietary supplements of alpha-tocopherol
      were given for 10 days before irradiation, and the same irradiation sequence was
      carried out. RESULTS: Small bowel crypt cell numbers, mucosal height, and goblet
      cell numbers were significantly protected from radiation effects by dietary alpha
      tocopherol pretreatment and by lumenal application of the vitamin. CONCLUSIONS:
      These studies indicate that vitamin E can serve as a partial protectant against
      acute irradiation enteritis, whether given as chronic oral systemic pretreatment
      or as a brief topical application.

PMID- 7574929
TI  - Restoration of CD44H expression in colon carcinomas reduces tumorigenicity.
AB  - OBJECTIVE: The functional consequences of reintroduction of the CD44H cell
      adhesion molecule into colon carcinomas were investigated. BACKGROUND: CD44 is a
      cell surface adhesion molecule that is normally present in numerous isoforms as a
      result of messenger RNA alternative splicing. Individual CD44 isoforms differ in
      their ability to enhance tumorigenic or metastatic potential when overexpressed
      on tumor cells. Reverse transcriptase-polymerase chain reaction analysis
      demonstrates that CD44H is down-regulated during transformation of normal colon
      mucosa to carcinoma. The functional consequences of CD44H down-regulation in
      colon carcinomas has not been clarified. METHODS: Tumor cell lines and fresh
      tissue specimens were examined for CD44 expression by Western blot analysis.
      CD44H cDNA and site-directed mutants of CD44H cDNA were transfected into colon
      carcinoma cells. Stable transfectants were examined for adhesion to hyaluronate,
      in vitro growth, and in vivo growth. RESULTS: CD44H expression was nearly
      undetectable in primary colon carcinomas and colon carcinoma cell lines. In
      contrast, normal mucosa expressed high levels of CD44H. When CD44H was
      reintroduced into colon carcinoma cells, their in vitro and in vivo growth was
      significantly reduced. This CD44H-mediated growth rate reduction required an
      intact cytoplasmic domain. CONCLUSIONS: Transformation of normal mucosa to colon
      carcinoma is associated with a down-regulation of CD44H, which consequently may
      enhance the growth rate and tumorigenicity.

PMID- 7574931
TI  - Forty-year appraisal of gastrinoma. Back to the future.
AB  - OBJECTIVE: The author analyzed potential survival determinants in gastrinoma to
      characterize a possible uniform staging system and to determine whether complete
      surgical resection improves expected survival. SUMMARY AND BACKGROUND DATA:
      Gastrinoma is an indolent yet malignant neuroendocrine tumor. The associated
      gastric acid hypersecretion can be controlled medically. Staging of gastrinoma is
      inconsistent and the role of surgical resection controversial. METHODS: Seventy
      four patients with gastrinoma with a minimum 5-year follow-up were assessed.
      Cox's proportional hazards regression model was used to examine the association
      of risk factors with survival. RESULTS: The following factors had no effect on
      survival: age at diagnosis, sex, presence of lymph node metastases, associated
      multiple endocrine neoplasia, and method of ulcer treatment. The three unique
      determinants of survival were primary tumor size (relative risk, 1.534; p =
      0.0005), liver metastases (relative risk, 2.947; p = 0.0209), and complete
      surgical resection (relative risk, 0.163; p = 0.0076). On the basis of these risk
      factors, a uniform staging system is proposed and predictive survival curves
      developed. CONCLUSIONS: The primary determinants of survival in gastrinoma are
      the size of the primary tumor and liver metastases. Complete surgical resection
      reduces mortality, regardless of other factors.

PMID- 7574932
TI  - Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than
      gastric juice alone. The need for surgical therapy re-emphasized.
AB  - OBJECTIVE: The author's goal was to determine the role of duodenal components in
      the development of complications of gastroesophageal reflux disease. SUMMARY AND
      BACKGROUND DATA: There is a disturbing increase in the prevalence of
      complications, specifically the development of Barrett's esophagus among patients
      with gastroesophageal reflux disease. Earlier studies using pH monitoring and
      aspiration techniques have shown that increased esophageal exposure to fluid with
      a pH above 7, that is, of potential duodenal origin, may be an important factor
      in this phenomenon. METHODS: The presence of duodenal content in the esophagus
      was studied in 53 patients with gastroesophageal reflux disease confirmed by 24
      hour pH monitoring. A portable spectrophotometer (Bilitec 2000, Synectics, Inc.)
      with a fiberoptic probe was used to measure intraluminal bilirubin as a marker
      for duodenal juice in the esophagus. Normal values for bilirubin monitoring were
      established for 25 healthy subjects. In a subgroup of 22 patients, a custom-made
      program was used to correlate simultaneous pH and bilirubin absorbance readings.
      RESULTS: Fifty-eight percent of patients were found to have increased esophageal
      exposure to gastric and duodenal juices. The degree of mucosal damage increased
      when duodenal juice was refluxed into the esophagus, in that patients with
      Barrett's metaplasia (n = 27) had a significantly higher prevalence of abnormal
      esophageal bilirubin exposure than did those with erosive esophagitis (n = 10) or
      with no injury (n = 16). They also had a greater esophageal bilirubin exposure
      compared with patients without Barrett's changes, with or without esophagitis.
      The correlation of pH and bilirubin monitoring showed that the majority (87%) of
      esophageal bilirubin exposure occurred when the pH of the esophagus was between 4
      and 7. CONCLUSIONS: Reflux of duodenal juice in gastroesophageal reflux disease
      is more common than pH studies alone would suggest. The combined reflux of
      gastric and duodenal juices causes severe esophageal mucosal damage. The vast
      majority of duodenal reflux occurs at a pH range of 4 to 7, at which bile acids,
      the major component of duodenal juice, are capable of damaging the esophageal
      mucosa.

PMID- 7574933
TI  - The delayed hypersensitivity response and host resistance in surgical patients.
      20 years later.
AB  - OBJECTIVE: A 20-year follow-up was conducted on research into the implications of
      a lack of a delayed-type hypersensitivity (DTH) skin test response among surgical
      patients. SUMMARY BACKGROUND DATA: The authors' original report showed that a
      failed DTH response was associated with increased hospital mortality, but the
      role of specific and nonspecific host defense elements, comorbid factors,
      nutritional supplementation, and the mechanism for anergy in this adverse outcome
      was unknown. METHODS: A data base of 4292 patients was analyzed and reported on
      individual studies designed to answer some of the above questions. RESULTS:
      Prospective studies showed a strong association between the DTH response and
      mortality: reactive patients, 2.9% (75/2576); anergic patients, 20.9% (239/1142,
      chi square = 265, p < 0.0000001). Antibody response to protein antigens was
      reduced in anergic patients. Antibody response to polysaccharide antigens was
      normal in all patients. The hallmark of anergy is a lack of T cells in the skin,
      as measured by mRNA signal (CD3) for T cells. The nonspecific component of host
      defense, as measured by circulating and exudate polymorphonuclear cell function,
      showed no statistically significant difference between elective reactive and
      elective anergic patients. Notwithstanding some mild malnutrition in anergic
      patients, parental nutrition failed to correct the DTH response or many of the
      cellular immune functions measured. CONCLUSIONS: Over the last 5 years, because
      of a reduction in overall patient mortality, the contribution of a reduced DTH
      response to septic related mortality has lost statistical significance in
      elective surgical patients. A reduced DTH response maintains its strong
      association to sepsis-related mortality in intensive care/trauma patients, and
      this is the group on which future research efforts should be concentrated.

PMID- 7574934
TI  - Tumor biology of infiltrating lobular carcinoma. Implications for management.
AB  - OBJECTIVE: The purpose of this study was to characterize the biologic
      determinants that affect the behavior and management of infiltrating lobular
      cancer. METHODS: A prospectively accrued data base containing 1548 breast cancer
      cases was queried for specific pathologic and mammographic features. From this
      data base, 777 patients treated and followed-up at the H. Lee Moffitt Cancer
      Center were reviewed, and comparisons were made between the following three
      histologic subgroups: 661 infiltrating ductal (ID), 42 infiltrating ductal plus
      infiltrating lobular (ID + IL), and 74 infiltrating lobular (IL). RESULTS:
      Comparisons of the three histologic forms of breast cancer demonstrated the
      following: 1. At diagnosis tumors with IL components were larger than those with
      ID components (p < 0.001); in addition, a greater percentage of IL cancers were
      T3 lesions (14.8%), compared with ID cancers (4.5%). 2. Sizes of IL tumors were
      underestimated frequently by mammographic examinations when compared with
      pathologic measurements (p < 0.001). 3. By comparison to ID tumors, increasing IL
      tumor size is less likely to be associated with an increased number of metastatic
      lymph nodes per patient (p = 0.09). 4. Infiltrating lobular cancers treated by
      lumpectomy with cytologic surgical margin analysis more often gave false-negative
      results than did ID cancers (p < 0.001). 5. Infiltrating lobular cancers treated
      by lumpectomy required conversion to mastectomy over 2 times more frequently than
      ID cancers treated by lumpectomy. 6. Mastectomy was performed more frequently
      than lumpectomy for the treatment of IL versus ID tumors (p = 0.039).
      CONCLUSIONS: Infiltrating lobular cancers are biologically distinct from ID
      cancers. Although lumpectomy may be performed safely in selected patients,
      multiple difficulties exist in the management of IL cancer, particularly when
      breast conservation is chosen.

PMID- 7574935
TI  - Autologous islet transplantation to prevent diabetes after pancreatic resection.
AB  - BACKGROUND: Extensive pancreatic resection for small-duct chronic pancreatitis is
      often required for pain relief, but the risk of diabetes is a major deterrent.
      OBJECTIVE: Incidence of pain relief, prevention of diabetes, and identification
      of factors predictive of success were the goals in this series of 48 patients who
      underwent pancreatectomy and islet autotransplantation for chronic pancreatitis.
      PATIENTS AND METHODS: Of the 48 patients, 43 underwent total or near-total (>
      95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas
      was dispersed by either old (n = 26) or new (n = 22) methods of collagenase
      digestion. Islets were injected into the portal vein of 46 of the 48 patients and
      under the kidney capsule in the remaining 2. Postoperative morbidity, mortality,
      pain relief, and need for exogenous insulin were determined, and actuarial
      probability of postoperative insulin independence was calculated based on several
      variables. RESULTS: One perioperative death occurred. Surgical complications
      occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a
      near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48
      patients had a transient increase in portal venous pressure after islet infusion,
      but no serious sequelae developed. More than 80% of patients experienced
      significant pain relief after pancreatectomy. Of the 39 patients who underwent
      total or near-total pancreatectomy, 20 (51%) were initially insulin independent.
      Between 2 and 10 years after transplantation, 34% were insulin independent, with
      no grafts failing after 2 years. The main predictor of insulin independence was
      the number of islets transplanted (of 14 patients who received > 300,000 islets,
      74% were insulin independent at > 2 years after transplantation). In turn, the
      number of islets recovered correlated with the degree of fibrosis (r = -0.52, p =
      0.006) and the dispersion method (p = 0.005). CONCLUSION: Pancreatectomy can
      relieve intractable pain caused by chronic pancreatitis. Islet
      autotransplantation is safe and can prevent long-term diabetes in more than 33%
      of patients and should be an adjunct to any pancreatic resection. A given
      patient's probability of success can be predicted by the morphologic features of
      the pancreas.

PMID- 7574936
TI  - A prospective randomized trial of pancreaticogastrostomy versus
      pancreaticojejunostomy after pancreaticoduodenectomy.
AB  - OBJECTIVE: The authors hypothesized that pancreaticogastrostomy is safer than
      pancreaticojejunostomy after pancreaticoduodenectomy and less likely to be
      associated with a postoperative pancreatic fistula. SUMMARY BACKGROUND DATA:
      Pancreatic fistula is a leading cause of morbidity and mortality after
      pancreaticoduodenectomy, occurring in 10% to 20% of patients. Nonrandomized
      reports have suggested that pancreaticogastrostomy is less likely than
      pancreaticojejunostomy to be associated with postoperative complications.
      METHODS: Between May 1993 and January 1995, the findings for 145 patients were
      analyzed in this prospective trial at The Johns Hopkins Hospital. After giving
      their appropriate preoperative informed consent, patients were randomly assigned
      to pancreaticogastrostomy or pancreaticojejunostomy after completion of the
      pancreaticoduodenal resection. All pancreatic anastomoses were performed in two
      layers without pancreatic duct stents and with closed suction drainage.
      Pancreatic fistula was defined as drainage of greater than 50 mL of amylase-rich
      fluid on or after postoperative day 10. RESULTS: The pancreaticogastrostomy (n =
      73) and pancreaticojejunostomy (n = 72) groups were comparable with regard to
      multiple parameters, including demographics, medical history, preoperative
      laboratory values, and intraoperative factors, such as operative time, blood
      transfusions, pancreatic texture, length of pancreatic remnant mobilized, and
      pancreatic duct diameter. The overall incidence of pancreatic fistula after
      pancreaticoduodenectomy was 11.7% (17/145). The incidence of pancreatic fistula
      was similar for the pancreaticogastrostomy (12.3%) and pancreaticojejunostomy
      (11.1%) groups. Pancreatic fistula was associated with a significant prolongation
      of postoperative hospital stay (36 +/- 5 vs. 15 +/- 1 days) (p < 0.001). Factors
      significantly increasing the risk of pancreatic fistula by univariate logistic
      regression analysis included ampullary or duodenal disease, soft pancreatic
      texture, longer operative time, greater intraoperative red blood cell
      transfusions, and lower surgical volume (p < 0.05). A multivariate logistic
      regression analysis revealed the factors most highly associated with pancreatic
      fistula to be lower surgical volume and ampullary or duodenal disease in the
      resected specimen. CONCLUSIONS: Pancreatic fistula is a common complication after
      pancreaticoduodenectomy, with an incidence most strongly associated with surgical
      volume and underlying disease. These data do not support the hypothesis that
      pancreaticogastrostomy is safer than pancreaticojejunostomy or is associated with
      a lower incidence of pancreatic fistula.

PMID- 7574937
TI  - The need for accurate risk-adjusted measures of outcome in surgery. Lessons
      learned through coronary artery bypass.
AB  - OBJECTIVE: The authors review the Pennsylvania Health Care Cost Containment
      Council reports on coronary artery surgery and compare this reporting structure
      to others, including the Society for Thoracic Surgeons database, currently used
      by their own program. The authors review the growing likelihood of a need for
      outcome measures for all of the surgical subspecialties. SUMMARY AND BACKGROUND
      DATA: Pressure from consumers and insurers will require surgical specialties to
      be graded by objective outcome measures. Practitioners must be prepared and
      become involved in the process. METHODS: The authors reviewed the data, which
      grades all of Pennsylvania's hospitals at which coronary artery bypass is
      performed. Apparently, the major risk factors commonly employed in most other
      risk adjustment schemes for cardiac surgery have been deleted, and the
      practitioners might be judged unfairly. The Pennsylvania system appears to be
      insurance driven to reward low-cost providers who operate on patients with the
      lowest risk. RESULTS: Review of data suggests that the Pennsylvania Health Care
      Cost Containment Council's annual publication, A Consumer's Guide for Coronary
      Artery Bypass Surgery, misrepresents fair risk adjustment in favor of lower-risk
      patients, thereby encouraging better score cards for those institutions with
      patients who are less ill. Data regarding charges for the procedure have not been
      risk adjusted or related to a regional economic index. CONCLUSIONS: Surgeons must
      prepare to better understand relevant models that evaluate outcome.
      Cardiothoracic surgery is one of the first specialties to feel the pressures of
      mandated evaluations, and the lessons learned in Pennsylvania should be
      applicable to other states and their practitioners.

PMID- 7574938
TI  - Surgical approach to short-bowel syndrome. Experience in a population of 160
      patients.
AB  - OBJECTIVE: The authors reviewed their experience with short-bowel syndrome to
      define the surgical approach to this problem in 160 patients. METHODS: Forty
      eight adults and 112 children were evaluated over a 15-year period. RESULTS:
      Seventy-one patients (44%) adapted to resection and took enteral nutrition alone.
      Forty-four patients (28%) were supported by parenteral nutrition (PN). Forty-five
      patients (28%) have had 49 surgical procedures. Fifteen patients with adequate
      intestinal length (> 120 cm in adults) but dilated dysfunctional bowel underwent
      stricturoplasty (n = 4) or tapering (n = 11). Thirteen patients (87%)
      demonstrated clinical improvement. Fourteen patients with shorter remnants (90
      120 cm) and rapid transit time received an artificial valve (n = 2) or a reversed
      segment (n = 1). All patients' conditions improved initially, but the reversed
      segment was revised or taken down. Fourteen patients with short remnants and
      dilated bowel underwent intestinal lengthening. Twelve patients' conditions
      improved (86%), one underwent transplantation, and one died. Sixteen patients
      with very short remnants (< 60 cm) and complications of PN underwent solitary
      intestine (n = 4) or combined liver-intestinal transplantation (n = 13). One-year
      graft survival was 65%. There have been five deaths. CONCLUSIONS: The surgical
      approach to short-bowel syndrome depends on the patient's age, remnant length and
      caliber, intestinal function, and PN-related complications. Nontransplant
      procedures have a role in the treatment of selected patients. Intestinal
      transplantation is emerging as a potential therapy for patients with significant
      PN-related complications.

PMID- 7574939
TI  - Heparin causes platelet dysfunction and induces fibrinolysis before
      cardiopulmonary bypass.
AB  - BACKGROUND: Platelet dysfunction and increased fibrinolysis are the most
      important etiologic factors in the hemostatic defect observed following the
      institution of cardiopulmonary bypass. This study examined the effects of heparin
      per se, administered before the institution of cardiopulmonary bypass, on
      platelet function and fibrinolysis. METHODS: Sampling was performed in 55
      patients undergoing cardiac operations before and 5 minutes after the routine
      administration of heparin, before the institution of cardiopulmonary bypass.
      RESULTS: Heparin administration resulted in a significant prolongation of the
      bleeding time (from 6.3 +/- 2.1 to 12.6 +/- 4.9 minutes; p < 0.00001), a
      significant reduction in the level of shed blood thromboxane B2 (from 1,152 +/-
      669 to 538 +/- 187 pg/0.1 mL; p = 0.00002), and an increase in the plasma levels
      of plasmin (from 11.8 +/- 9.7 to 125.4 +/- 34.8 U/L; p < 0.0001) and D-dimer
      (from 571.3 +/- 297.1 to 698.5 +/- 358.6 micrograms/mL; p = 0.05). There were no
      significant differences before and after heparin administration in the plasma
      levels of fibrinogen, plasminogen, tissue plasminogen activator, antiplasmin,
      antithrombin III, and von Willebrand factor. CONCLUSIONS: Heparin, independent of
      cardiopulmonary bypass, causes both platelet dysfunction and increased
      fibrinolysis. The use of an alternative anticoagulant or a lower dose of heparin
      in conjunction with heparin-coated surfaces might improve the hemostatic balance
      during open heart operations.

PMID- 7574940
TI  - Perioperative donor bone marrow infusion augments chimerism in heart and lung
      transplant recipients.
AB  - BACKGROUND: We and others have demonstrated that a low level of donor cell
      chimerism was present for years after transplantation in tissues and peripheral
      blood of heart and lung recipients; it was associated, in the latter, with a
      lower incidence of chronic rejection. To augment this phenomenon, we initiated a
      trial combining simultaneous infusion of donor bone marrow with heart or lung
      allotransplantation. METHODS: Between September 1993 and January 1995, 15
      nonconditioned patients received either heart (n = 10) or lung (n = 5) allografts
      concurrently with an infusion of unmodified donor bone marrow (3.0 x 10(8)
      cells/kg), and were maintained on immunosuppressive regimen consisting of
      tacrolimus and steroids. RESULTS: There was no complication associated with the
      infusion of donor bone marrow. Chimerism was detectable in 73% of bone marrow
      augmented patients up to the last sample tested. Of the 5 control recipients who
      did not receive bone marrow infusion, only 1 had detectable chimerism by flow on
      postoperative day 15, which dwindled to an undetectable level by postoperative
      day 36. None of the patients had evidence of donor-specific immune modulation by
      mixed lymphocyte reaction. CONCLUSIONS: The combined infusion of donor bone
      marrow and heart or lung transplantation, without preconditioning of the
      recipient, is safe and is associated with an augmentation of donor cell
      chimerism.

PMID- 7574941
TI  - Microvascular reactivity after crystalloid, cold blood, and warm blood
      cardioplegic arrest.
AB  - BACKGROUND: The effects of three techniques of cardioplegic arrest on endothelium
      dependent microvascular function of the right and left ventricles were examined
      in a canine model of cardiopulmonary bypass. METHODS: Oxygenated cold crystalloid
      cardioplegia and cold blood cardioplegia groups, (n = 11 each) had hypothermic
      cardiopulmonary bypass (28 degrees C), topical cooling, antegrade arrest, and
      intermittent antegrade delivery. A warm blood cardioplegia group (n = 11) had
      normothermic cardiopulmonary bypass (37 degrees C), antegrade arrest, and
      continuous antegrade delivery. All groups underwent cardioplegic arrest for 1
      hour followed by 1 hour of reperfusion. Dogs that did not have instrumentation
      were used as controls (n = 10). Coronary microvessels (100 to 200 microns in
      internal diameter) were examined in a pressurized, no-flow state with video
      microscopic imaging and electronic dimension analysis. RESULTS: Ischemic arrest
      with cold crystalloid cardioplegia significantly (p < 0.05) impaired endothelium
      dependent relaxations in both ventricles to acetylcholine (left ventricle, 69% +/
      4%, and right ventricle, 73% +/- 5%, versus control left ventricle, 100% +/-
      0.3%, and control right ventricle, 100% +/- 0.3%) and the calcium ionophore (left
      ventricle, 70% +/- 6%, and right ventricle, 68% +/- 3%, versus control left
      ventricle, 98% +/- 1%, and control right ventricle, 98% +/- 1%). In the cold
      blood cardioplegia group, endothelium-dependent relaxations to acetylcholine
      (left ventricle, 96% +/- 1%, and right ventricle, 87% +/- 4%) and the calcium
      ionophore (left ventricle, 88% +/- 3%, and right ventricle, 78% +/- 7%) were
      preserved. In the warm blood cardioplegia group, endothelium-dependent responses
      to acetylcholine (92% +/- 3%) and the calcium ionophore (96% +/- 1%) were
      preserved in the left ventricle, but the right ventricle showed reduced (p <
      0.05) reactivity to the endothelium-dependent acetylcholine (77% +/- 8%) and the
      calcium ionophore (69% +/- 8%). Endothelium-independent relaxation to sodium
      nitroprusside was similar to controls in all groups for both ventricles, thus
      indicating normal smooth muscle responsiveness. CONCLUSIONS: Cardioplegic arrest
      with cold blood cardioplegia preserved the endothelium-dependent response in the
      right and left ventricles, whereas cold crystalloid cardioplegia impairs this
      response. Warm blood cardioplegia preserved the endothelium-dependent response in
      the left ventricle, but this response was reduced in the right ventricle. This
      suggests that blood cardioplegia and hypothermia may be important in protection
      of microvascular endothelium and that the right ventricle may be more vulnerable
      to damage than the left ventricle.

PMID- 7574942
TI  - Free latissimus dorsi flap for chest wall repair after complete resection of
      infected sternum.
AB  - BACKGROUND: Radical debridement, followed by muscle flap cover, has significantly
      reduced morbidity and mortality of infected sternotomy wounds. The pectoralis
      major, rectus abdominis, and greater omentum flaps are most commonly used,
      whereas the latissimus dorsi muscle is rarely employed. METHODS: In 7 patients
      with persistent infection and necrosis of the sternum, radical and extensive
      debridement including the sternum, costochondral arches, manubrium and
      sternoclavicular joints was performed. A free latissimus dorsi flap was used for
      soft tissue reconstruction without additional stabilization of the chest wall.
      RESULTS: All flaps survived without revision of the anastomosis. In the follow-up
      period (22 months to 5 years) no recurrent infection was observed. Three patients
      died during the study period (3 to 24 months after operation) due to causes not
      related to sternum operation. No additional weakness, pain, or restricted
      movements of the shoulders due to missing sternum was observed. CONCLUSIONS: Our
      findings suggest that the use of free latissimus dorsi flap after complete
      sternectomy for infection has several advantages: it provides abundant tissue to
      allow radical and extensive debridement, obliterates completely the dead space,
      and helps to control infection. Even without additional chest wall reconstruction
      it gives enough stability to allow pain-free normal daily activities.

PMID- 7574943
TI  - CABG in octogenarians: early and late events and actuarial survival in comparison
      with a matched population.
AB  - BACKGROUND: With important demographic changes in cardiac surgical practice, more
      older patients are undergoing complex cardiac operations. Controversy exists as
      to whether the expenditure of healthcare resources on the growing elderly
      populations represents an effective approach in maintaining a meaningful quality
      of life. METHODS: From January 1982 through April 1991, 121 consecutive
      octogenarians underwent a surgical procedure that included coronary artery bypass
      grafting. Retrospective review of patient medical records was performed; follow
      up information was obtained via telephone contact with the patient, the patient's
      family, or the patient's physician. RESULTS: There were 67 men (55%) and 54 women
      (45%). Mean age was 82.1 years (range, 80 to 89 years). Sixty-nine percent of the
      patients were having class III or IV symptoms. There were 11 hospital deaths
      (9.1%); risk factors included longer cardiopulmonary bypass time (p = 0.01),
      higher preoperative left ventricular end-diastolic pressure (p = 0.02), advanced
      age (p = 0.05), history of renal disease (p = 0.02), and myocardial infarction (p
      = 0.04). Late death occurred in 34 patients (30.9%) at a mean of 27 months
      postoperatively; univariate risk factors included chronic obstructive pulmonary
      disease (p = 0.009), higher left-ventricular end-diastolic pressure (p = 0.03),
      and recent myocardial infarction (p = 0.03). Actuarial survival, including
      hospital death, was 32.8% at 80 months, compared with 37.6% for an age; sex; and
      race-matched population (p > 0.3). Most late survivors (84%) were in New York
      Heart Association class I or II. CONCLUSIONS: We conclude that coronary artery
      bypass grafting can be performed in octogenarians with an acceptable, although
      increased risk. Hospital survivors have a good late functional status but are at
      risk for pulmonary and other atherosclerosis-related events, which impair overall
      survival.

PMID- 7574944
TI  - Determinants of operative mortality in octogenarians undergoing coronary bypass.
AB  - BACKGROUND: The elderly segment of the population is increasing rapidly, and
      surgeons are being asked to consider patients more than 80 years old as
      candidates for coronary bypass. The objective of this study was to identify risk
      factors that may adversely affect mortality as well as analyze functional
      outcomes and survival in octogenarians undergoing coronary bypass. METHODS: From
      July 1989 through February 1994, 300 consecutive patients 80 years of age and
      older underwent coronary artery bypass grafting. There were 176 men (58.7%) and
      124 women (41.3%) with a mean age of 80.9 years (range, 80 to 99 years).
      Preoperatively, 274 patients (91.3%) had disabling angina, 76 (25.3%) had left
      main coronary stenosis greater than 50%, and 293 patients (98.3%) were in New
      York Heart Association class III or IV. RESULTS: The overall hospital mortality
      was 11.0% (33/300) with an elective mortality of 9.6% (23/240), urgent mortality
      of 11% (5/45), and emergent mortality of 33.3% (5/15). Significant independent
      predictors of operative mortality were preoperative renal dysfunction,
      postoperative pulmonary insufficiency, postoperative renal dysfunction, use of
      intraaortic balloon pumping, and sternal wound infection. The actuarial survival
      for patients discharged from the hospital was 74.6% +/- 5.6% (standard error of
      the mean) at 54 months. CONCLUSIONS: A favorable outcome may be expected when
      coronary artery bypass grafting is performed in patients 80 years of age or older
      with severe angina.

PMID- 7574945
TI  - Results of mitral valve reconstruction in children with rheumatic heart disease.
AB  - BACKGROUND: Between January 1988 and November 1994, we developed techniques of
      reconstructing diseased mitral valves in patients with rheumatic heart disease.
      Four hundred thirteen patients underwent mitral valve repair using these
      techniques. Of these, 125 children and adolescents less than 15 years of age form
      the study group. METHODS: The mean age was 8.9 +/- 4.3 years (range, 5 to 15
      years). One hundred seventeen patients (93.6%) had rheumatic heart disease. There
      were 72 boys (57.6%) and 53 girls (42.4%). All of these patients were
      symptomatic: New York Heart Association class III or IV. Mitral regurgitation
      alone was present in 49 patients (39.2%), and combined mitral stenosis and
      regurgitation were present in 76 patients (60.8%). Surgical techniques included
      commissurotomy (n = 70; 56%), annuloplasty (n = 122; 97.6%), chordal shortening
      (n = 46; 36.8%), cusp thinning (n = 27; 5.6%), and associated procedures for
      tricuspid valve disease (6 patients) and aortic valve disease (2 patients).
      RESULTS: The operative mortality rate was 4.8% (6 patients), and late deaths
      occurred in 1.6% (2 patients). Follow-up was 378.25 patient-years. In 15
      patients, severe mitral regurgitation developed after a mean follow-up of 37.14
      +/- 20.47 months (seven reoperations). At 6 years, actuarial and event-free
      survival rates were 92.1% +/- 3.19% and 75% +/- 8.18%, respectively. One patient
      (0.15%/patient-year) had transient right hemiparesis. None had anticoagulation
      related bleeding. CONCLUSION: Mitral valve reconstruction in children and
      adolescents with rheumatic mitral regurgitation provides satisfactory early
      results. Progression of disease is the most important risk factor for
      reoperation. The technique described provided stable repair in the majority of
      patients.

PMID- 7574946
TI  - Evaluation of the hemodynamic performance of small CarboMedics aortic prostheses
      using dobutamine-stress Doppler echocardiography.
AB  - BACKGROUND: The well-known correlation between prosthetic valve orifice area and
      transvalvular gradients has raised concerns about the presence of significant
      residual gradients when the size of the prosthesis that can be implanted is
      limited by the presence of a small aortic annulus. METHODS: Dobutamine-stress
      Doppler echocardiography was used to evaluate the hemodynamic performance of
      small CarboMedics aortic prostheses (19 mm and 21 mm) in 18 patients (16 women;
      mean age, 64 years) who had undergone aortic valve replacement 23.5 +/- 19 months
      (standard deviation) previously. Dobutamine infusion was started at a rate of 5
      micrograms.kg-1.min-2 and increased to 10 and 20 micrograms.kg-1.min-2 at 15
      minute intervals. Pulsed and continuous wave Doppler studies were performed at
      rest and at the end of each stage. Effective orifice area, performance index, and
      discharge coefficient of both valves were calculated, and peak and mean velocity
      and pressure drop across the prostheses were measured. RESULTS: Heart rate and
      cardiac output increased by 74% and 94%, respectively, and mean arterial blood
      pressure decreased by 9% at maximum stress. Effective orifice area, discharge
      coefficient, and performance index were comparable in both valve sizes at rest
      and maximum stress. Also, there was no significant difference in mean
      transvalvular pressure drop (gradient) for 19-mm and 21-mm prostheses at rest
      (8.1 +/- 8.4 and 4.8 +/- 3.8 mm Hg) or maximum stress (15.1 +/- 14.2 and 8.8 +/-
      5.8 mm Hg, respectively). No significant correlation could be demonstrated
      between transvalvular pressure drop and patient's body surface area. CONCLUSIONS:
      These data show that 19-mm and 21-mm CarboMedics aortic prostheses exhibit
      equally favorable hemodynamic performance with minimal pressure gradient, both at
      rest and under stress conditions.

PMID- 7574947
TI  - The CarboMedics valve: midterm follow-up with analysis of risk factors.
AB  - BACKGROUND: This study examined the midterm results with the CarboMedics
      prosthetic valve. METHODS: From 1987 through 1991 a total of 569 patients
      received the CarboMedics prosthesis. RESULTS: Early mortality was 4.9% and
      related to emergency operation, presence of diabetes mellitus, coronary artery
      disease, preoperative New York Heart Association class, duration of
      cardiopulmonary bypass, and aortic cross-clamp time. Midterm follow-up with
      respect to mortality was 100% complete. All patients were followed up in the
      hospital after 1 year. In addition 86% of the patients responded to a
      questionnaire. Mean follow-up was 3 years (range, 0 to 5.6 years). Cumulative
      survival at 1 and 4 years was 91.2% +/- 1.2% and 83.7% +/- 1.8%, respectively.
      Five patients experienced obstructive valve thrombosis (0.3%/patient-year), 16
      patients had major thromboembolic events (0.9%/patient-year), and 10 patients had
      major warfarin-related bleeding (0.6%/patient-year) requiring hospitalization or
      blood transfusions. Eight patients were reoperated on for paraprosthetic leak
      (0.4%/patient-year). Prosthetic valve endocarditis developed in 4 patients
      (0.2%/patient-year). No structural valve failure was observed. CONCLUSIONS:
      Midterm follow-up demonstrates that the CarboMedics mechanical prosthesis is
      reliable and has an acceptable rate of valve-related complications.

PMID- 7574948
TI  - Left ventricular end-systolic volume index in patients with ischemic
      cardiomyopathy predicts postoperative ventricular function.
AB  - BACKGROUND: We investigated the usefulness of the preoperative left ventricular
      end-systolic volume index (LVESVI) as a predictor of postoperative ventricular
      function. METHODS: We retrospectively reviewed the records of 310 patients who
      underwent coronary artery bypass grafting and identified 20 patients with
      ischemic cardiomyopathy with a preoperative ejection fraction less than 0.30. We
      determined the preoperative and postoperative ejection fraction, LVESVI, and left
      ventricular enddiastolic volume index using biplane left cineventriculography.
      Patients were divided into groups depending on whether their preoperative LVESVI
      was less than 100 mL/m2 (group A, n = 10) or greater than 100 mL/m2 (group B, n =
      10). RESULTS: The mean ejection fraction increased significantly after coronary
      artery bypass grafting in group A from 0.25 +/- 0.05 to 0.40 +/- 0.09 (p < 0.01),
      but did not change significantly in group B (0.26 +/- 0.05 versus 0.23 +/- 0.06).
      The mean LVESVI decreased significantly in group A from 83.2 +/- 13.7 to 61.7 +/-
      20.4 mL/m2 after operation (p < 0.05), but did not change significantly in group
      B (124.7 +/- 21.0 versus 121.5 +/- 37.6 mL/m2). In group B, 4 patients had signs
      of congestive heart failure during the follow-up period and had to be
      rehospitalized. CONCLUSIONS: The mean ejection fraction improved significantly
      after coronary artery bypass grafting in patients with a preoperative LVESVI less
      than 100 mL/m2, despite the presence of a global left ventricular ejection
      fraction less than 0.30. Our results suggest that the preoperative LVESVI
      predicts the postoperative status and left ventricular function in patients with
      ischemic cardiomyopathy.

PMID- 7574949
TI  - Coronary artery reoperation through the left thoracotomy with hypothermic
      circulatory arrest.
AB  - BACKGROUND: The left thoracotomy approach to avoid injury of the patent old graft
      and the myocardium with mid sternal reentry at coronary artery reoperation.
      METHODS: The left thoracotomy approach was used in 13 patients. There were 11 men
      and 2 women with a mean age of 63 years, ranging from 39 to 75 years. Three
      patients were having their third coronary bypass operation. In 11 patients,
      distal anastomoses were performed under circulatory arrest with moderate
      hypothermia. In the other 2 patients, distal anastomoses were performed on a
      beating heart. No aortic cross-clamp was applied in all patients. The mean number
      of distal anastomoses was 1.8; the grafted vessels were 11 anterior descending, 3
      diagonal, 8 circumflex, and 1 posterolateral coronary arteries. Used grafts were
      17 saphenous veins, 4 left internal thoracic arteries, and 2 gastroepiploic
      arteries. Inflow sites of the free graft were descending aorta in 10 patients and
      left subclavian artery in 3 patients. RESULTS: All patients were alive and well
      at the mean follow-up of 16 months, and all grafts were patent. CONCLUSIONS: The
      left thoracotomy approach is safe and effective for reoperation on the left
      coronary artery system, and circulatory arrest is convenient and safe for
      performing distal anastomosis.

PMID- 7574950
TI  - Hemopump treatment in patients with postcardiotomy heart failure.
AB  - BACKGROUND: This study examined the use of the Hemopump to treat low cardiac
      output syndrome after cardiopulmonary bypass. METHODS: We used the Hemopump
      temporary cardiac assist system in 29 patients with severe left ventricular
      dysfunction after open heart operations from September 1991 to November 1994.
      RESULTS: Five patients were excluded from the study due to initial patient/device
      related problems. Ten patients died in the operating room or early during the
      stay in the intensive care unit due to progressive biventricular failure.
      Fourteen patients (58.3%) were weaned from the device, and all of them were later
      discharged. In a subgroup of patients (54%) in whom we had a more aggressive
      approach for early insertion of the pump, the survival rate was 85%. Preoperative
      Higging risk score was significantly related to survival. CONCLUSIONS: The
      Hemopump can effectively unload a failing left ventricle with preservation of
      multiorgan perfusion. A minor decrease in kidney function was observed in most
      patients, but none of the surviving patients needed hemodialysis. One patient
      required a short period of peritoneal dialysis to get rid of fluid overload.
      Hemolysis or platelet dysfunction was not a clinical problem.

PMID- 7574951
TI  - Upper extremity vascular access for continuous arteriovenous hemofiltration and
      dialysis after cardiac operations.
AB  - BACKGROUND: There is increasing interest in the use of continuous arteriovenous
      hemofiltration/dialysis for treatment of profound renal failure after
      cardiovascular operations. Vascular access for this is usually accomplished by
      percutaneous cannulation of the femoral artery and vein, with the inherent risks
      of vascular trauma, patient immobilization, hemorrhage, or infectious
      complications. METHODS: Fifteen (0.36%) of 4,166 patients receiving
      cardiovascular surgical procedures sustained postoperative renal failure
      requiring treatment with continuous arteriovenous hemofiltration/dialysis. Each
      patient had creation of acute arteriovenous forearm access using a modified Allen
      Brown shunt. Shunts were monitored continuously for hemorrhage, malfunction,
      infection, and thrombus, and were explanted when no longer required. RESULTS:
      Sixteen shunts were implanted in 15 patients over the 41-month period. All shunts
      functioned satisfactorily, with the duration of implantation ranging from 1 to 64
      days. There were no infectious or hemorrhagic complications. CONCLUSIONS: The
      acute creation of a simple forearm shunt for postoperative continuous
      arteriovenous hemo-filtration/dialysis is preferred over femoral arterial and
      venous cannulation because it can be constructed rapidly and easily in the
      operating room or at the bedside, has a low complication rate, is available for
      immediate use, may be left in place indefinitely, does not interfere with patient
      mobilization or ambulation, and is easily removed.

PMID- 7574952
TI  - Effects of high-dose aprotinin on renal function in aortocoronary bypass
      grafting.
AB  - BACKGROUND: To reduce blood consumption in cardiac surgery, aprotinin has been
      widely used for years. Because aprotinin is metabolized in the kidney, damage of
      the renal system has been discussed. METHODS: To study these possibly unfavorable
      effects of aprotinin, a prospective, randomized, placebo-controlled study of 20
      patients undergoing aortocoronary bypass operations was performed. A placebo
      group P was compared with group A, in which patients received high-dose aprotinin
      according to the "Hammersmith" regimen. Renal function was assessed for 5
      postoperative days using sodium dodecyl sulfate gel electrophoresis and
      quantitative protein analysis of the urine. RESULTS: During and after the
      operation, temporary renal dysfunction was found in all patients, with a
      substantial increase of all investigated indices. The alpha 1-microglobulin level
      in the urine was significantly increased in the aprotinin group for 5 days in
      comparison with the placebo group, with a maximum on the third postoperative day
      (64.8 +/- 13.7 versus 21.0 +/- 6.5 mg/L; p < 0.05). Similarly, after sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, the bands of proteins
      filtrated in the renal tubular system were almost tripled in the aprotinin group
      5 days postoperatively (5.0 +/- 0.8 versus 2.1 +/- 0.2; p < 0.05). Although urine
      production was significantly increased in group A (4789 +/- 580 versus 3653 +/-
      492 mL/24 h postoperatively; p < 0.05), no relevant changes in serum or urine
      creatinine levels could be observed in either group. CONCLUSIONS: Patients
      undergoing aortocoronary bypass operations demonstrate a temporary renal
      dysfunction. Aprotinin impairs renal function in addition by overloading the
      tubular reabsorption mechanisms. Patients with normal renal function
      preoperatively--as were included in this study--are able to compensate for both
      the perioperative renal dysfunction caused by the extracorporeal circulation and
      the additional tubular damage due to aprotinin.

PMID- 7574953
TI  - Right ventricular dysfunction in low output syndrome after cardiac operations:
      assessment by transesophageal echocardiography.
AB  - BACKGROUND: Low output syndrome after cardiac operations is associated with high
      morbidity and mortality rates. The contribution of right ventricular dysfunction
      to this syndrome has not been fully characterized. The purpose of this study was
      to evaluate the utility of transesophageal echocardiography to identify the
      frequency and the in-hospital mortality from right ventricular dysfunction in
      patients with this syndrome. METHODS: Seventy-five consecutive patients
      undergoing transesophageal echocardiography for low output syndrome early after
      cardiac operations were evaluated. The findings from transesophageal
      echocardiography were correlated with the type of surgical procedure, cross-clamp
      time, right heart hemodynamics, and coronary angiography. RESULTS: Right
      ventricular systolic dysfunction occurred in 36 patients (42%); in 17 patients it
      was isolated and in 19 patients it occurred in combination with left ventricular
      dysfunction. Postoperative right ventricular dysfunction was not uniformly
      associated with important right coronary artery disease or with prolonged
      ischemic time during cardiopulmonary bypass. Hemodynamic data were not useful to
      distinguish the group with postoperative right ventricular dysfunction. Patients
      with right ventricular dysfunction had a high (44%) in-hospital mortality rate.
      CONCLUSIONS: Right ventricular dysfunction occurs frequently in patients with low
      output syndrome after cardiac operations and is associated with a high in
      hospital mortality rate. Better understanding of the mechanisms causing
      postoperative right ventricular dysfunction may provide insight for preventing
      this complication.

PMID- 7574954
TI  - Normothermic versus mild hypothermic retrograde blood cardioplegia: a
      prospective, randomized study.
AB  - BACKGROUND: Continuous retrograde blood cardioplegia has been introduced as a
      promising alternative for myocardial protection during cardiac operations,
      although the optimal conditions for its delivery have been poorly studied.
      METHODS: We randomized a prospective series of 101 patients to receive either
      retrograde warm (37 degrees C) or mild hypothermic (28 degrees to 29 degrees C)
      blood cardioplegia during elective coronary artery bypass grafting. Warm blood
      cardioplegia was delivered to the aortic root until the heart was arrested, after
      which the regimen was switched to retrograde and continued either as warm or mild
      hypothermic cardioplegia. Oxygen consumption and transcardiac pH differences
      during aortic cross-clamping were determined, and postoperative creatine kinase
      MB efflux, hemodynamic recovery, and clinical complications monitored. RESULTS:
      Clinical characteristics, cardioplegia delivery rates, aortic cross-clamp and
      cardiopulmonary bypass times, and the number of distal anastomoses were similar
      in both patient groups. Short intermissions in cardioplegia delivery during
      construction of distal anastomoses were allowed, the ischemia time in the mild
      hypothermic group being somewhat longer (8.3% +/- 1.1% versus 5.1% +/- 0.8% of
      cross-clamp time; p = 0.05). Myocardial oxygen consumption was lower in the mild
      hypothermic group (2.49 +/- 0.23 versus 3.93 +/- 0.33 mL/min at 30 minutes of
      cross-clamping; p < 0.01), and the transcardiac pH difference was smaller (0.05
      +/- 0.01 versus 0.07 +/- 0.01 at 30 minutes of cross-clamping; p < 0.03).
      Postoperative creatine kinase-MB levels were higher in the normothermic group.
      Heart rate was higher and left ventricular stroke work index smaller in the warm
      group, but otherwise there were no major differences between the groups in
      hemodynamic recovery. The number of postoperative complications was also similar
      in both groups. CONCLUSIONS: Although both normothermic (37 degrees C) and mild
      hypothermic (28 degrees to 29 degrees C) retrograde blood cardioplegia, when
      delivered in near-continuous fashion, will offer safe myocardial protection
      during coronary artery bypass grafting, mild hypothermia seemed to provide
      somewhat better protection under the conditions prevailing here. The effects of
      different cardioplegia temperatures should perhaps be tested further in patients
      with recent myocardial infarction, unstable angina, or severely depressed left
      ventricular function.

PMID- 7574955
TI  - Changing surgical CPI valuation relationships: a method of determination (1970
      1995).
AB  - Surgeons have, over the past 7 years, experienced a significant decrease in
      valuation of their services. This has been accomplished by use of the Resource
      Based Relative Value System, and its interpretation and modification by various
      agencies of the federal government. Congress recently mandated a study of
      practice costs that could result in further reductions of up to 30%. In
      anticipation of this further reduction, it is important to understand in as
      accurate a way as possible what has happened thus far to the value for surgical
      services. Simple percentage in decrease of fees is well understood, but their
      decrease in relation to the cost of a constant market basket of goods has not
      been well publicized. We present a simple method for determining the change in
      value for any procedure or service done by a surgeon in relation to the cost of a
      constant market basket of goods for any period of time from 1970 to 1995. For
      example, the increase in the cost for the constant market basket of goods between
      1972 and 1992 is shown to be 236%. The increase in value for a typical
      cardiothoracic procedure in the same time period was 52%. The valuation for this
      procedure has actually declined 55% from 1972 to 1992, relative to the market
      basket of goods. The service that would buy the complete basket in 1972 will now
      buy only 45% of the basket.

PMID- 7574956
TI  - Successful repair of a ruptured postinfarct pseudoaneurysm of the left ventricle.
AB  - We report a case of a 60-year-old woman who underwent emergency surgical repair
      of a ruptured pseudoaneurysm of the left ventricle 10 days after acute myocardial
      infarction. The repair consisted of oversewing the rupture (2 cm long) on the
      posterior wall under cardiopulmonary bypass. The patient made a satisfactory
      recovery.

PMID- 7574957
TI  - Valvuloplasty in traumatic aortic insufficiency due to subtotal tear of the
      intima.
AB  - Aortic regurgitation is one of the usual pathologic findings necessitating valve
      replacement in cardiac surgery. Several diseases may result in leaflet
      incompetence. Circumferential intimal tear of the aortic root with prolapse of
      the aortic valve commissures is a rare cause of aortic incompetence. We report
      the repair of the aortic wall and valve in 1 patient with such a tear 6 months
      after an important thoracic trauma. Three months after the aortic valve
      reconstruction the patient is in good condition and fully asymptomatic.

PMID- 7574958
TI  - Cholelithoptysis and empyema formation after laparoscopic cholecystectomy.
AB  - Thoracic complications of laparoscopic operations are rare. We describe a case of
      cholelithoptysis due to a gallstone sequestered in the middle lobe after
      laparoscopic cholecystectomy.

PMID- 7574959
TI  - Endovascular stent-grafting after arch aneurysm repair using the "elephant
      trunk".
AB  - A 68-year-old woman with severe chronic obstructive pulmonary disease, aortic
      valvular insufficiency, and diffuse thoracic aortic aneurysm underwent aortic
      valve replacement and separate Dacron graft replacement of the ascending aortic
      and arch aneurysms using the elephant trunk technique. She was discharged on the
      tenth postoperative day. Five months later, she underwent endovascular stent
      graft repair of the descending thoracic aortic aneurysm. She recovered
      uneventfully, and was discharged on the third postoperative day. Follow-up
      computed tomography at 6 months demonstrated exclusion of all flow into the
      descending thoracic aortic aneurysm. The elephant trunk technique followed by
      endovascular stent-grafting of the descending thoracic component is a potential
      therapeutic option in selected high-risk patients with diffuse aortic aneurysmal
      disease.

PMID- 7574960
TI  - Radical excisional therapy and total cardiac transplantation for recurrent atrial
      myxoma.
AB  - We describe the management of a recurrent atrial myxoma extending to the
      pulmonary veins and superior vena cava. Deep hypothermia and circulatory arrest
      with left atrial and caval excision was required to achieve complete resection of
      the tumor. The patient is alive and well without evidence of tumor recurrence 18
      months after transplantation. Radical en bloc cardiac resection is feasible in
      selected cases of cardiac tumors.

PMID- 7574961
TI  - Modified surgical palliation for a rare type of L-transposition with aortic
      atresia.
AB  - L-Transposition of the great arteries with aortic atresia without an outlet
      chamber is a rare congenital heart defect. We used a modified Norwood procedure
      incorporating a type of direct coronary transfer for successful palliation of
      this lesion in a neonate.

PMID- 7574962
TI  - Management of intraaortic balloon entrapment.
AB  - Two cases of intraaortic balloon entrapment were presented. In patient 1,
      urokinase was injected into the gas driver lumen of the intraaortic balloon
      catheter, then it could be removed. In patient 2, the intraaortic balloon was
      removed retrogradely through the left axillary artery. If the entrapped
      intraaortic balloon is encountered, it is effective to try a clot-lysis method
      initially, followed by a surgical approach through a left axillary artery.

PMID- 7574963
TI  - Paradoxical embolism in the presence of right-to-left shunt due to tricuspid
      occlusion.
AB  - The case of a 33-year-old woman suffering from a paradoxical peripheral embolism
      in the presence of a right-to-left shunt at the level of an ostium secundum
      defect is presented. A functional stenosis of the tricuspid valve due to
      obstruction through a thrombotic atrial mass was found to be responsible for the
      right-to-left shunt. Treatment consisted of peripheral embolectomy, removal of
      the atrial mass, and closure of the atrial septum defect.

PMID- 7574964
TI  - Defibrillator patch electrode constriction: an underrecognized entity.
AB  - Pericardial constriction associated with the placement of intrapericardial
      defibrillator patches is a rare occurrence that is reported only one tenth as
      often in defibrillator patients as in patients undergoing other types of cardiac
      operations. Although this discrepancy may be attributable to a lower incidence of
      constriction with the defibrillator patch electrode procedure, it may also
      indicate a failure to recognize that progressive right heart failure and signs of
      low cardiac output that could be due to pericardial constriction and not
      progressive systolic dysfunction. Because surgical removal of the patches and
      decortication of the epicardial surface is the only effective therapy, it is
      important to recognize this uncommon, but profoundly debilitating entity.

PMID- 7574965
TI  - Umbilical artery flow velocity during maternal cardiopulmonary bypass.
AB  - The fetal death rate associated with cardiac operations using cardiopulmonary
      bypass in pregnant women is as high as 9.5% to 29%. We present a case in which
      fetal heart rate and umbilical artery flow velocity waveforms were continuously
      monitored by transvaginal ultrasonography and analyzed in relation to events of
      the cardiopulmonary bypass. Our findings suggest that hypothermia during
      cardiopulmonary bypass has potentially deleterious effects on the fetus and
      should be avoided if possible.

PMID- 7574966
TI  - Embolization of biologic glue during repair of aortic dissection.
AB  - A 72-year-old patient was operated on because of an acute type A aortic
      dissection with the primary entry located in the aortic arch and with retrograde
      involvement of the ascending aorta. Complete replacement of the aortic arch and
      the ascending aorta was performed after the dissected aortic layers had been
      readapted and sealed with gelatin-resorcin-formaldehyde biologic glue.
      Postoperative neurologic status was judged to be normal. The patient died 3 weeks
      postoperatively of septic shock. Postmortem examination of the brain revealed
      several small lesions, and microscopy showed very small particles of polymerized
      glue in the afferent vessels of ischemic cerebral and meningeal regions.

PMID- 7574967
TI  - Simultaneous repair of multiple traumatic aortic tears.
AB  - A 34-year-old man suffered simultaneous tears of his distal ascending and mid
      descending thoracic aorta secondary to blunt trauma. Repairs of both injuries
      were performed via a median sternotomy approach followed by a left lateral
      thoracotomy using two separate methods of cardiopulmonary bypass.

PMID- 7574968
TI  - Post-stenting enlarging false aneurysm of a saphenous vein graft.
AB  - Stenting seems to be a definitive procedure after failed balloon coronary
      angioplasty. This report describes a case of redo coronary bypass grafting and
      concomitant resection of enlarging false aneurysm of a saphenous vein graft that
      developed secondary to stenting for recurrent stenosis after serial percutaneous
      transluminal coronary angioplasty. It warns us of a pitfall in catheter
      intervention in an aged saphenous vein graft.

PMID- 7574969
TI  - Dacron coronary graft obstruction after composite graft replacement of aortic
      root.
AB  - Obstruction of the left coronary ostial anastomosis is a rare late complication
      after composite graft replacement of the ascending aorta and the aortic valve
      with separate Dacron coronary grafts. Intimal proliferation caused by the
      turbulent blood flow at this site may be the cause of the obstruction, which is
      considered a possible cause of late cardiac events such as sudden death and
      global myocardial infarction. We describe a case of tight stenosis at the left
      coronary ostial anastomosis in a 38-year-old woman with Marfan's syndrome who had
      undergone a composite graft replacement that employed separate Dacron coronary
      grafts.

PMID- 7574970
TI  - Bronchioloalveolar carcinoma and congenital cystic adenomatoid malformation.
AB  - We report on a 42-year-old woman in whom was discovered a symptomless peripheral
      radiologic excavated lesion of the lung, which actually existed 3 years before.
      All investigations were negative. A segmentectomy was performed. Histopathologic
      examination proved a bronchioloalveolar carcinoma in contact with a type I
      congenital cystic malformation of the lung. Such a malformation can be diagnosed
      late in adult life. The epithelial cells of the malformation might predispose to
      slow proliferation and malignancy, enhanced by smoking habits.

PMID- 7574971
TI  - Direct coronary sinus cannulation during cardioplegic infusion.
AB  - Retrograde cardioplegia has gained popularity as an improved method of myocardial
      protection. Cannulation of the coronary sinus, at times, may be difficult or
      impossible when the transatrial approach is used. We herein report a technique of
      direct cannulation of the coronary sinus, which appears to be safe and effective.

PMID- 7574972
TI  - Reducing bleeding after replacement of the aortic root.
AB  - Bleeding after replacement of the aortic root continues to be a major surgical
      problem. We detail two reliable methods, which are quick and simple to perform,
      that minimize surgical bleeding after aortic root replacement.

PMID- 7574973
TI  - New technique for sternal osteosynthesis.
AB  - In our department, we have developed a new method for sternal osteosynthesis.
      This technique uses steel threads and a sternal retractor. The removable valves
      are removed and placed with a two-pulley device, which allows good osteosynthesis
      without assistance or effort.

PMID- 7574974
TI  - Evolution of pulmonary resection techniques and review of the bronchus-first
      method.
AB  - The dissection technique of pulmonary resection evolved in the period 1930 to
      1950. Surgeons had to cope with the location of disease, bronchiectasis,
      tuberculosis, and lung cancer, as well as associated bronchial secretions, hilar
      pathology, and the status of anesthesiology. Two basic hilar dissection methods
      emerged, the anterior vessel-first sequence and the posterior bronchus-first
      method. The bronchus-first method is particularly suitable for pneumonectomy,
      right upper lobectomy, and posterior-apical segmentectomy of this lobe as well as
      ease of lymph node removal. This technique, as a primary method of lung
      resection, does not appear to be emphasized in teaching curricula and supporting
      atlases or texts.

PMID- 7574975
TI  - Postoperative management of cerebral air embolism: gas physiology for surgeons.
AB  - Cerebral gaseous microemboli are present in most, if not all, cardiopulmonary
      bypass-assisted operations. Fortunately, the great majority are subclinical.
      Clinically significant cases of cerebral air embolism are largely underdiagnosed,
      undertreated, and underreported. The management of cerebral air embolism has been
      challenged due to the lack of prospective, randomized studies. Preventive
      measures that have been implemented throughout the years, resulting from
      empirically acquired knowledge, have avoided frequent major mishaps. Perfusion
      accidents, in which massive amounts of gas are pumped into patients, are managed
      intraoperatively by common-sense heroic measures which, at best, remove 50% of
      the embolized gas. Postoperative confirmation of a neurologic insult after a
      cardiopulmonary bypass-assisted operation, in which a cerebral air embolism is
      likely the source, is one of the most distressing situations a surgical team has
      to confront, due in part to the lack of pathognomonic diagnostic tools and to the
      absence of a "scientifically proven" (supported by prospective, randomized
      studies) therapeutic regimen. In lieu of the latter, we present the physical and
      physiologic bases that will justify the use of several therapeutic tools when
      facing a suspected CAE. These tools, when applied rationally, will represent some
      of the most innocuous modalities in the medical armamentarium.

PMID- 7574977
TI  - 1988: Surgery of the descending thoracic aorta: spinal cord protection with the
      Gott shunt. Updated in 1995.

PMID- 7574976
TI  - Cardiac surgery and cold-reactive proteins.
AB  - Cold agglutinins are commonly found in sera of healthy persons. They rarely
      become clinically apparent due to their activity at low temperatures. In these
      patients, cardiovascular operations requiring hypothermia can result in
      complications such as hemolysis, renal failure, and myocardial damage and can
      cause unexpected morbidity and mortality. The literature on cold-reactive
      proteins is reviewed, and methods of diagnosis and management related to cardiac
      surgery are suggested. Ideally all patients should be routinely tested
      preoperatively for the antibodies, and appropriate changes in cardiopulmonary
      bypass and myocardial management plans should be made in positive patients.
      Preoperative plasmapheresis may be a useful adjunct, especially in patients
      requiring operation under profound hypothermia and circulatory arrest. Currently,
      warm heart surgery appears to be the most expedient method. Unexpected detection
      of agglutination during operation or hemolysis after operation requires a
      specific treatment plan.

PMID- 7574978
TI  - 1988: Paced skeletal muscle for dynamic cardiomyoplasty. Updated in 1995.

PMID- 7574979
TI  - Amiodarone for ventricular tachycardia after coronary artery bypass grafting.

PMID- 7574980
TI  - Topical aprotinin in cardiac operations.

PMID- 7574981
TI  - Hemodynamic effects of atrio-biventricular pacing.

PMID- 7574982
TI  - Who's afraid of Kety-Schmidt?

PMID- 7574983
TI  - Thoracoscopic pulmonary resection.

PMID- 7574984
TI  - Therapeutic implications for heparin-induced thrombocytopenia and thrombosis.

PMID- 7574985
TI  - Normothermia, hypothermia, and postoperative bleeding.

PMID- 7574986
TI  - Hemostatic modification in aortic root replacement with composite graft.

PMID- 7574987
TI  - Surgical management of chronic obstructive pulmonary disease.

PMID- 7574988
TI  - Coronary operations in octogenarians: can we select the patients?

PMID- 7574989
TI  - A comprehensive curriculum for thoracic surgery: survey of opinions from program
      directors and residents.
AB  - BACKGROUND: The Comprehensive Thoracic Surgery Curriculum was developed to
      provide program directors with a basis for planning instruction and evaluating
      residents, program practices, and outcomes. A survey design was selected to
      obtain opinions about the curriculum from a large group of people, ie, all
      program directors and all active residents. METHODS: Two parallel instruments
      were developed: one to be completed by program directors and one to be completed
      by active residents. Responses were collated for directors and residents, entered
      into a computerized database, and compared using the chi 2 statistic. RESULTS: A
      response rate of 93% was obtained from the directors and 79% from the residents.
      The survey demonstrates broad-based support for a comprehensive curriculum by the
      respondents. Current perceptions of and expectations for the curriculum are
      diverse and regionalized. Serious concerns are expressed about quality issues and
      particularly the environment for residency education. CONCLUSIONS: The thoughtful
      responses of our colleagues will guide leaders who will implement the curriculum
      for thoracic surgery. Strategies for change will necessarily focus on the
      prerequisite curriculum.

PMID- 7574990
TI  - Decortication is a valuable option for late empyema after collapse therapy.
AB  - BACKGROUND: Infection of previous collapse therapy spaces may raise challenging
      problems. This study evaluated a conservative surgical approach based on
      decortication. METHODS: Since 1979, 28 patients (mean age, 60 +/- 6 years) have
      presented at an average of 37 +/- 7 years after artificial pneumothorax for
      tuberculosis. Diagnosis of empyema was made on follow-up in 12 patients and on
      symptoms in 16 patients. Mean vital capacity was 66% +/- 16% of normal.
      Microorganisms were isolated in 13 patients (Aspergillus fumigatus in 5,
      Mycobacterium tuberculosis in 4, anaerobes in 4). Decortication was made in 24
      patients, associated with thoracoplasty in 4, and with partial lung resection in
      2 patients. Thoracoplasty alone was performed in 2 patients, and 2 patients
      underwent an extrapleural pneumonectomy. RESULTS: Both extrapleural
      pneumonectomies were complicated with empyema requiring thoracoplasty, resulting
      in one postoperative death. Operative mortality after decortication was nil. Mean
      intraoperative blood loss during decortication was 1,830 +/- 1,310 mL. All
      patients were extubated within 24 hours, except 1 patient who was ventilator
      dependent preoperatively. Prolonged air leaks were common (mean duration of
      drainage, 16 +/- 11 days), but ultimately sealed. Existence of symptoms was
      predictive of prolonged air leaks (p < 0.01). CONCLUSIONS: We conclude that
      decortication may provide a one-stage cure avoiding the hazards of extrapleural
      pneumonectomy; the nonfunctioning remaining lung may resolve the space problem.

PMID- 7574991
TI  - Superficial esophageal carcinoma.
AB  - BACKGROUND: The detection of superficial esophageal carcinomas by surveillance
      endoscopy and the downstaging of advanced carcinomas to superficial carcinomas by
      induction therapy have increased the number of patients with these carcinomas
      undergoing resection. The natural history of these carcinomas is not well
      defined. METHODS: To evaluate the results of surgical resection and identify
      predictors of improved survival, a retrospective review of (1) patients with
      superficial esophageal carcinoma at presentation (SECP) and (2) patients with
      advanced carcinomas that were downstaged to no residual carcinoma or superficial
      esophageal carcinoma after induction therapy (SECD) was conducted. RESULTS: There
      were 54 patients with SECP (19 Tis and 35 T1). Survival was significantly better
      for patients with Tis carcinomas (85.3% at 5 years) and patients with
      intramucosal T1 carcinomas (79.4%) than for patients with submucosal T1
      carcinomas (16.3%) (p = 0.007 and p = 0.045, respectively). Survival at 5 years
      for the 49 patients without regional lymph node metastases (N0) was 65.2%,
      whereas none of the 5 patients with regional lymph node metastases (N1) have
      survived more than 3 years (p = 0.054), and 3 died of recurrent disease. There
      were 21 patients with SECD (13 T0, 2 Tis, and 6 T1). Survival at 4 years was
      58.2%. In this group, survival was not related to depth of tumor invasion (p =
      0.76) or regional lymph node status (p = 0.68). CONCLUSIONS: We conclude that (1)
      patients with Tis and intramucosal T1 SECP have a significantly better survival
      than those with submucosal T1 SECP, (2) patients with N0 SECP have a
      significantly better survival than those with N1 SECP, and (3) survival of
      patients with SECD is not related to depth of tumor invasion or regional lymph
      node status.

PMID- 7574992
TI  - Lung transplantation for congenital pulmonary vein stenosis.
AB  - BACKGROUND: Congenital pulmonary vein stenosis is a uniformly fatal disease when
      left untreated. Transcatheter techniques (for example, balloon dilation and stent
      placement) have proved to be only temporizing measures, and previous surgical
      attempts at treatment of this entity have provided little improvement and few
      survivors. METHODS: Over the last 4 years, 6 patients with congenital pulmonary
      vein stenosis have been treated at our institution, 3 of whom underwent bilateral
      sequential lung transplantation. RESULTS: The 3 patients who underwent bilateral
      lung transplantation are alive and well 6 to 24 months after transplantation. The
      other 3 died of complications of the disease before donor lungs became available.
      CONCLUSIONS: Making the diagnosis of congenital pulmonary vein stenosis requires
      a high index of suspicion, and referral for lung transplantation should be made
      as soon as the diagnosis is reached. Lung transplantation has resulted in good
      quality short to medium-term survival for 3 patients with this otherwise
      untreatable disease.

PMID- 7574993
TI  - Thymoma: a multivariate analysis of factors predicting survival.
AB  - BACKGROUND: Despite complete surgical excision, malignant thymomas often recur
      with resultant death. We reviewed our series to determine which factors
      independently predict survival after surgical resection. METHODS: A retrospective
      analysis of patients operated on for thymoma between 1949 and 1993 at Memorial
      Sloan-Kettering Cancer Center was performed. Clinical data were collected from
      chart review. Only patients with a pathology report confirming the diagnosis of
      thymoma were included in this analysis. Kaplan-Meier survival curves were
      generated and comparisons of survival analyzed by log rank test. Multivariate
      analysis was performed by the Cox proportional hazard model. RESULTS: One hundred
      eighteen patients with thymoma underwent operation. There were 86 complete
      resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka
      staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%),
      and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years.
      Tumor recurred in 25 (29%) of 86 completely resected thymomas. Stage of disease
      (p = 0.03) was the only independent prognostic factor affecting recurrence. By
      multivariate analysis, stage (p = 0.003), tumor size (p = 0.0001), histology (p =
      0.004), and extent of surgical resection (p = 0.0006) were independent predictors
      of long-term survival. CONCLUSIONS: Patients with stage I disease require no
      further therapy after complete surgical resection. Neoadjuvant therapy should be
      considered for patients with large tumors and invasive disease.

PMID- 7574994
TI  - Uncut Collis-Nissen gastroplasty: early functional results.
AB  - BACKGROUND: This study reviewed the short-term results of the uncut Collis-Nissen
      gastroplasty. METHODS: From 1990 through 1993, 27 consecutive patients (16 men,
      11 women) underwent an uncut Collis-Nissen gastroplasty. Mean age was 59 years
      (range, 30 to 75 years). Three patients had a previous failed antireflux
      procedure. Indications for operation were gastroesophageal reflux disease
      resistant to medical treatment in 18 patients and symptomatic hiatal hernia in 9
      patients. Fourteen patients had Barrett's esophagus and 4 had a peptic stricture.
      Complete esophageal function testing including barium swallow, endoscopy,
      manometry, and 24-hour pH recording was performed in 26 of 27 patients
      preoperatively and postoperatively. RESULTS: Five patients (19%) had
      complications, which included atelectasis in 2, cardiac dysrhythmia in 2, and
      prolonged ileus in 1. There were no operative deaths. Follow-up was complete in
      all patients and ranged from 8 to 45 months (mean, 22 months). Subjectively,
      symptoms of reflux were resolved in all patients. Six patients complain of slow
      esophageal emptying and 3 have occasional episodes of dysphagia. None required
      postoperative dilation. Ulcers and erosions healed in all 26 patients who
      underwent endoscopy but recurred in 2 at 21 and 36 months postoperatively. Mean
      lower esophageal sphincter gradient increased from 8.3 mm Hg preoperatively to
      14.6 mm Hg (p = 0.0001). Total percent of acid exposure decreased from 8.0%
      preoperatively to 1.7% (p = 0.003). CONCLUSIONS: We conclude that the uncut
      Collis-Nissen procedure provides acceptable short-term control of
      gastroesophageal reflux disease.

PMID- 7574995
TI  - Esophageal resection for recurrent achalasia.
AB  - BACKGROUND: This study examined esophageal resection as treatment for recurrence
      or treatment complications of achalasia. METHODS: From 1976 through 1992, 37
      patients (20 men and 17 women) underwent esophageal resection after initial
      surgical treatment for achalasia. The median age was 56 years (range, 19 to 84
      years). Initial surgical treatment consisted of modified Heller myotomy in 28
      patients, combined myotomy and antireflux procedure in 6, and antireflux
      procedure alone in 3. Twenty-six patients required an additional surgical
      procedure before esophageal resection (70.3%). Indication for esophageal
      resection was obstructive symptoms in 30 patients, cancer in 3, bleeding in 2,
      and perforation during dilation in 2. Reconstruction was established with the
      stomach in 26 patients, colon in 6, and small bowel in 5. Anastomosis was at the
      cervical level in 20 patients (54.1%) and intrathoracic in 17 (45.9%). RESULTS:
      There were two operative deaths (5.4%), both caused by intraoperative hemorrhage
      during transhiatal resection. Twelve patients (32.4%) had complications, which
      included cardiac dysrhythmia in 3, cervical anastomotic leak in 2, transient
      vocal cord paralysis in 2, pneumonia in 2, pulmonary embolus in 2, and
      reexploration for bleeding in 1. Follow-up was complete in all patients and
      ranged from 1.4 to 16 years (median, 6.3 years). Excellent or good long-term
      functional results were present in 32 patients (91.4%). CONCLUSIONS: Esophageal
      resection provides reasonable long-term functional results in patients with
      recurrence or treatment complications of achalasia. In our experience,
      transhiatal resection is associated with increased morbidity and mortality.

PMID- 7574996
TI  - Anesthetic techniques for pediatric thoracoscopy.
AB  - BACKGROUND: Since 1981, we have performed 68 thoracoscopic procedures in 62
      patients aged 7 months to 21 years. METHODS: We reviewed the anesthetic and
      ventilation strategy used for each procedure to determine which anesthetic
      strategies are safe and effective for particular children and conditions.
      RESULTS: Regional anesthesia with sedation was used for six procedures in 5
      patients with a mean age of 16 years (range, 9 to 21 years). One patient required
      conversion to general anesthesia. General anesthesia with one-lung ventilation
      was attempted for 18 procedures in 17 patients with a mean age of 12 years
      (range, 7 months to 18 years). Two patients required conversion to two-lung
      anesthesia secondary to pulmonary intolerance. One of these patients and 2 others
      required thoracotomy. General anesthesia with two-lung ventilation was used for
      44 procedures in 41 patients with a mean age of 9 years (range, 1 to 17 years).
      There were no anesthesia-related difficulties. CONCLUSIONS: Regional anesthesia
      should be limited to the older, more cooperative patient. General anesthesia with
      one-lung ventilation is useful in adolescents, as they tolerate collapse of one
      lung well, and it is particularly desirable for procedures requiring exposure of
      the mediastinum and for talc pleurodesis. General anesthesia with two-lung
      ventilation can be used in any age group but is generally necessary for infants
      and small children, as they often will not tolerate the collapse of one lung, and
      in the larger child or adolescent with severe pulmonary compromise.

PMID- 7574997
TI  - Video-assisted thoracic surgery: primary therapy for spontaneous pneumothorax?
AB  - BACKGROUND: This study assessed the role of video-assisted thoracic surgery
      (VATS) in current therapy for spontaneous pneumothorax. METHODS: We compared a
      retrospective series of 89 patients treated conventionally with a consecutive
      group of 30 patients undergoing VATS pleural abrasion. The 89 earlier patients
      were predominantly male (81%). Treatment groups included observation/aspiration
      (7 or 17%), tube thoracostomy (32 or 36%), multiple tubes (7 or 9%), and
      thoracotomy (43 or 48%). Of the 30 patients treated with VATS, 18 (66%) were
      male. Primary indications for operation were recurrent pneumothorax (17) and
      persistent air leak (9). RESULTS: Hospital lengths of stay (LOS) for the earlier
      group were 5 days for simple tube and 7 days for primary thoracotomy; LOS for
      initial intervention followed by thoractomy exceeded 15 days in all subgroups.
      The average LOS in the VATS group was 13 days; 6 patients treated with primary
      VATS (no chest tube) had a mean LOS of 6.5 days. Complications included 3 (10%)
      prolonged air leaks (more than 7 days) and 2 (7%) early recurrences. CONCLUSIONS:
      We do not recommend VATS as primary therapy for spontaneous pneumothorax; tube
      thoracostomy remains the treatment of choice. However, we strongly support
      surgical intervention early (3 days) in patients with a persistent air leak, and
      as primary therapy in a nonurgent situation if standard indications exist. This
      study shows no advantage of VATS over conventional thoracotomy in hospital stay
      or complication rate.

PMID- 7574998
TI  - Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema.
AB  - BACKGROUND: Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous
      emphysema by means of a contact neodymium:yttrium-aluminum garnet laser was
      evaluated by a retrospective analysis of the first consecutive 500 procedures in
      443 patients. The indication for thoracoscopic laser pneumoplasty was intractable
      dyspnea. METHODS: Advanced age (mean age, 67 years), high oxygen dependency
      (70%), steroid use (46%), and markedly diminished physical capacity (2% bedridden
      and 27% wheelchair-bound) were noted. Thoracoscopic laser pneumoplasty was
      carried out under general anesthesia and one-lung ventilation. Type 3 bullae (381
      procedures) were contracted by contact neodymium:yttrium-aluminum garnet laser
      and type 4 bullae (199 procedures) excised. The operative mortality rate was
      4.8%. RESULTS: Subjective improvement was reported by 87% of the patients. Follow
      up functional evaluation was available in 229 patients, which showed highly
      significant improvement. A comparison of preoperative and postoperative
      functional tests between type 3 and 4 bullae patients showed no significant
      difference, except the latter had higher decrease in airway resistance, residual
      volume, and total lung capacity. CONCLUSIONS: Thoracoscopic laser pneumoplasty is
      an effective treatment for both type 3 and 4 bullous emphysema with an acceptable
      risk.

PMID- 7574999
TI  - Videothoracoscopic excision of thoracic neurogenic tumors.
AB  - BACKGROUND: Videothoracoscopic surgery is a new procedure for treating neurogenic
      tumors of the thorax. Feasibility and utility of this technique are not yet well
      defined. METHODS: Over a 26-month period, 26 neurogenic tumors of the thorax were
      treated in five general thoracic surgery centers performing videothoracoscopic
      surgery. Indications and contraindications for this new procedure and initial
      results were retrospectively studied. RESULTS: Contraindications to
      videothoracoscopy included intraspinal extension of the tumor (n = 3), spinal
      artery involvement (n = 2), tumors more than 6 cm in diameter borderline located
      within the thorax (n = 2), and middle mediastinal location (n = 1).
      Videothoracoscopy was performed in 18 patients. Conversion to thoracotomy was
      required in 3. In 1 patients, subsequent chest wall resection was performed
      because of malignancy. Postoperative hospital stay was uneventful. It was shorter
      after videothoracoscopy. Postsurgical pain was more acute in patients who had
      thoracotomy or conversion to thoracotomy. CONCLUSIONS: Videothorascopy is a good
      alternative for managing neurogenic tumors of the thorax when deemed feasible.
      There is a tendency toward a shorter hospital stay with less pain in patients
      treated by this new procedure.

PMID- 7575000
TI  - Effect of ischemic injury on subsequent rat lung allograft rejection.
AB  - BACKGROUND: It has been suggested that the frequency and severity of allograft
      rejection may be related to the degree of allograft ischemia. The purpose of this
      study was to determine whether ischemic insult correlates with lung allograft
      rejection. METHODS: Forty-eight left lung transplants were performed from Lewis
      donor rats into F344 recipient rats. Allografts were divided into two groups
      based on the degree of ischemic insult. Transplantation was performed immediately
      (group 1, minimum injury) or after 18 hours of cold (1 degree C) preservation
      (group 2, severe injury). Allografts were evaluated radiographically based on
      aeration scores (0 = opaque to 6 = normal). Animals were randomly sacrificed on
      days 7, 14, or 21 for histologic and immunohistochemical evaluation of rejection.
      RESULTS: On postoperative day 3, significantly lower aeration score was
      demonstrated in group 2 (3.69 +/- 1.71) compared to group 1 (5.0 +/- 1.09) (p <
      0.05) as a result of the difference in reperfusion injury. However, by day 7 and
      thereafter, there was no significant difference. Histologic rejection was present
      by day 7 and peaked at day 14 with no significant difference between groups.
      There was also no difference in CD4+, CD8+ infiltrating lymphocyte population or
      expression of class II major histocompatibility complex antigen on bronchial
      epithelium. CONCLUSIONS: We conclude that ischemic injury in rat lung allograft
      does not correlate with the onset or severity of rejection.

PMID- 7575001
TI  - Morphologic alterations and cytokinetic studies of tracheal autograft epithelium
      in rabbits.
AB  - BACKGROUND: Although tracheobronchoplasty has been used widely in the field of
      thoracic surgery, few details of the morphologic changes in and cytokinetics of
      the graft epithelium have been reported. The aim of this study was to focus on
      these aspects in autografted rabbit tracheas. METHODS: Resected cervical tracheas
      were anastomosed immediately after removal, retrieved on postoperative days 1
      through 28, and examined morphologically. Mitotic and bromodeoxyuridine-labeling
      indices of the graft epithelium were analyzed. RESULTS: On postoperative days 1
      to 4, the graft epithelium showed focal desquamation at the anastomoses. Ciliated
      cells disappeared during postoperative days 4 to 7 and then increased gradually.
      Nonciliated cells retained a somewhat columnar shape on postoperative days 4 to
      7, except at denuded foci. Thereafter, the grafts were covered completely with
      pseudostratified mucociliary epithelium. On postoperative day 4, both indices
      were maximal and appeared higher at the anastomotic than midgraft sites.
      CONCLUSIONS: Most of the graft epithelium was preserved during acute ischemia and
      then started to regenerate. The increased regenerative activity near the
      anastomoses may be attributable to mechanical damage or different nutritional
      conditions.

PMID- 7575002
TI  - Lung preservation threshold in a compromised septic lung injury model.
AB  - BACKGROUND: Discrepancy between clinical and research works in lung
      transplantation could be due to differences between compromised clinical donor
      lungs and intact research lungs. The purpose of this laboratory study was to
      produce compromised lungs to compare with normal ones. METHODS: Sprague-Dawley
      rats were continuously infused with lipopolysaccharide (5 mg/kg) for 24 hours
      before organ harvest. Lungs were stored in University of Wisconsin solution at 4
      degrees C for the following period: group 1: intact lungs, no storage (n = 12);
      group 2: septic lungs, no storage (n = 6); group 3: septic lungs for 6 hours (n =
      5); and group 4: septic lungs for 12 hours (n = 5). All lungs were reperfused for
      2 hours with venous blood using an isolated, pulsatile perfused lung system.
      RESULTS: Experimental variables were comparable between groups 1, 2, and 3. All
      septic lungs stored for 12 hours (group 4) failed within 1 hour of perfusion.
      CONCLUSIONS: These results indicate that compromised lungs with septic injury
      functioned at near control levels after 6 hours of preservation. Six hours may be
      a safe limit for human donor lungs, all of which are compromised in some way by
      the time of harvest.

PMID- 7575003
TI  - Treatment of multiple primary squamous cell carcinomas of the lung.
AB  - BACKGROUND: The prevalence of multiple primary bronchogenic cancers, especially
      squamous cell carcinoma, has been increasing as a result of improvements in early
      detection and cancer therapy. MATERIALS: We treated 14 patients with multiple
      squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded
      to 2.3% of all squamous cell carcinoma patients undergoing resection. RESULTS:
      Two patients had peripheral secondary tumors and underwent segmentectomy or
      partial resection of the lung with good results. The secondary lesions were
      superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium
      yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of
      the nodular or polypoid type with suspected deep invasion or invasion extending
      beyond the bronchial wall based on the bronchoscopic findings. They underwent
      parenchymal-sparing limited bronchoplasty with excellent results. Three patients
      had more advanced tumor with massive invasion outside the bronchial wall without
      lymph node metastases, 1 patient underwent sleeve lobectomy with long survival,
      and the other 2 patients without operation died of bleeding or had recurrence.
      One patient with stage IIIA (T2 N2) secondary cancer who underwent lobectomy died
      14 months after the second operation. CONCLUSIONS: The surgical treatment of
      multiple squamous cell carcinoma is justified and limited operation using
      bronchoplastic techniques provides superior results.

PMID- 7575004
TI  - Systemic obstruction in univentricular hearts: surgical options for neonates.
AB  - BACKGROUND: The surgical management for bridging patients with univentricular
      heart and systemic obstruction to a Fontan procedure remains controversial.
      METHODS: Twenty-seven of 96 patients with univentricular heart and unobstructed
      pulmonary blood flow referred for surgical palliation were seen with systemic
      obstruction. Twenty-six were neonates with coarctation of the aorta in 21 and
      subaortic stenosis in 5. In 8 other patients, subaortic stenosis developed after
      initial pulmonary artery banding. Four different palliative procedures were
      performed: coarctation repair with pulmonary artery banding (group I, n = 15);
      Norwood or Damus-Kaye-Stansel or arterial switch operation (group II, n = 9);
      coarctation repair with pulmonary artery banding and bulboventricular foramen
      enlargement (group III, n = 2); and orthotopic heart transplantation with
      coarctation repair (group IV, n = 1). RESULTS: The mortality rate was 34.3% (n =
      12) for all patients, 53.3% in group I, 33.3% in group II (p = 0.003 versus group
      I), and 50% in group III. Nine patients (8 in group I and 1 in group II) had
      development of subaortic stenosis and underwent a subsequent procedure: Damus
      Kaye-Stansel operation in 5, arterial switch operation in 3, and bulboventricular
      foramen enlargement in 1. Three had a concomitant or subsequent Fontan procedure
      and 2, a bidirectional Glenn procedure. In group II, 1 patient underwent a
      subsequent Fontan procedure and another, a bidirectional Glenn anastomosis. Six
      of the 8 patients with subaortic stenosis after initial pulmonary artery banding
      underwent a second stage consisting of a Damus-Kaye-Stansel procedure (n = 3),
      bulboventricular foramen enlargement (n = 2), or creation of an aortopulmonary
      window (n = 1). Three had a concomitant Fontan procedure and 2, a bidirectional
      Glenn procedure. Actuarial 4-year survival was 65.5% +/- 8.4% (70% confidence
      limits) for all patients; it was 40% +/- 13.3% in group I and 66.6% +/- 16.3% in
      group II (p < 0.05). CONCLUSIONS: Initial management of patients with
      univentricular heart and systemic obstruction by Norwood-like procedures provides
      a better outcome. Success of the Fontan operation relies on the ability to
      provide timely relief of subaortic stenosis.

PMID- 7575005
TI  - Right-to-left veno-arterial shunting for right-sided circulatory failure.
AB  - BACKGROUND: Right-sided circulatory failure, a complication of heart
      transplantation and left ventricular assist device use, results in decreased
      cardiac output due to diminished flow across the pulmonary circuit. We
      hypothesized that creation of a controlled right-to-left shunt would result in
      decompression of the right ventricle and improved systemic cardiac output at
      tolerable oxygen saturations. We also hypothesized that a peripheral veno
      arterial shunt is physiologically superior to a central shunt. METHODS: Right
      atrial-femoral artery and right atrial-left atrial shunts were created in a large
      animal model (calf). Right-sided circulatory failure was induced by banding the
      pulmonary artery. Hemodynamic measures and blood gas determinations were obtained
      during nonshunted and shunted states. RESULTS: Peripheral and central shunts
      resulted in decreased right-sided pressures and increased cardiac output.
      Arterial oxygen saturation remained greater than 90% during shunting. The
      peripheral shunt had the added advantage of decreasing left ventricular end
      diastolic pressure and left ventricular stroke work. CONCLUSIONS: A controlled
      right-to-left shunt improved hemodynamics and cardiac output in a large animal
      model with right-sided circulatory failure. This strategy may be useful in the
      management of transplant and left ventricular assist device recipients with
      perioperative right-sided circulatory failure. Our studies also indicate that
      creation of a peripheral shunt has both physiologic and technical advantages over
      a central shunt.

PMID- 7575006
TI  - Mechanical dysfunction in the border zone of an ovine model of left ventricular
      aneurysm.
AB  - BACKGROUND: The pathophysiology of regional mechanical dysfunction in the border
      zone (BZ) region of left ventricular aneurysm was studied in an ovine model using
      magnetic resonance imaging tissue-tagging and regional deformation analysis.
      METHODS: Transmural infarcts were created in adult Dorsett sheep (n = 8) by
      ligation of the distal homonymous coronary artery and were allowed to mature into
      left ventricular aneurysms for 8 to 12 weeks. Animals were imaged subsequently
      using double oblique magnetic resonance imaging with radiofrequency tissue
      tagging. Short axis slices were selected for analysis that included predominantly
      the septal component of the aneurysm as well as adjacent BZ regions in the
      anterior and posterior ventricular walls. Dark grid patterns of magnetic
      presaturations were placed on the myocardium and tracked as they deformed during
      the diastolic, isovolumic systolic, and systolic ejection phases of the cardiac
      cycle. Regional ventricular wall strains were calculated in BZ regions and
      regions remote from the aneurysm and compared with strains measured in
      corresponding regions from normal control sheep (n = 6). RESULTS: Diastolic
      midwall circumferential strains (fiber extensions) were relatively preserved, but
      abnormal circumferential lengthening strains were observed in the BZ regions
      during isovolumic systole. Peak circumferential strains ranged from 0.04 to 0.07
      in the BZ regions but averaged -0.05 in the normal hearts (p = 0.002 for the
      anterior BZ and p = 0.001 for the posterior BZ). Midwall end-systolic fiber
      strains were depressed in the anterior BZ (-0.03 to -0.09 for the BZ versus -0.11
      for the normal heart, p < 0.0001) but not in the posterior BZ (p = 0.19).
      CONCLUSIONS: Our data support the theory that the stretching of BZ fibers during
      isovolumic systole contributed to a reduction in fiber shortening during systolic
      ejection and thus reduced the overall contribution of these fibers to forward
      ventricular output.

PMID- 7575007
TI  - Carpentier-Edwards standard porcine bioprosthesis: clinical performance to
      seventeen years.
AB  - BACKGROUND: The role of porcine bioprostheses in cardiac valve replacement has
      been under review for several years. The literature deals primarily with age as a
      determinant of durability, as well as the intermediate-term performance of
      various prostheses. The performance of the Carpentier-Edwards first-generation
      standard porcine bioprosthesis is presented over the long-term with further
      documentation on age determinants. METHODS: The "Guidelines for Reporting
      Morbidity and Mortality After Cardiac Valvular Operations" were used for
      definitions of valve-related complications, categorization, and statistical
      methods. The valve-related complications were evaluated in a time-related manner
      by actuarial life-table techniques. The Lee-Desu statistic test was used for
      comparison of performance by valve positions and age groups. Hazard function
      rates were demonstrated for complications and composites. RESULTS: Of the
      Carpentier-Edwards porcine bioprostheses implanted in 1,195 patients (1,214
      operations, 1,315 valves) commencing in 1975 the early mortality was 7.6% (92).
      The early mortality without concomitant procedures was 6.1% and with 11.7%. The
      late mortality was 5.3% per patient-year; 4.6% patient-year without and 7.5% per
      patient-year with concomitant procedures. The valve-related causes of late
      mortality (131) were thromboembolism (41), antithromboembolic hemorrhage (14),
      prosthetic valve endocarditis (20), nonstructural dysfunction (12), and
      structural valve deterioration (44). The valve-related deaths (early, 7; late,
      124) were 21.2% of the total 617 total deaths. Reoperation for valve-related
      complications was performed in 406 patients (4.1% per patient-year), of which 327
      were for structural valve deterioration (3.3% per patient-year). Mortality for
      reoperation was 0.5% per patient-year (49 patients) or 12.1%. Of the 49 deaths,
      33 were caused by structural valve deterioration. The linearized occurrence rate
      for thromboembolism was 1.6% per patient-year (major, 0.9% per patient-year, and
      minor, 0.7% per patient-year). The fatal thromboembolic rate was 0.4% per patient
      year (41), undifferentiated by valve position. The freedom from thromboembolism
      was 76% at 17 years (p = not significant by valve position) (major, 87%; fatal,
      93%). The freedom from prosthetic valve endocarditis was 92% at 17 years (p = not
      significant by valve position). The freedom from reoperation, at 15 years, was
      38%: aortic (AVR), 55%; mitral (MVR), 20%; and multiple valve replacement (MR),
      24% (p < 0.05 AVR > MVR, MR). The freedom from structural valve deterioration, at
      15 years, was 41%; AVR, 58%; MVR, 21%; MR, 36% (p < 0.05 AVR > MVR, MR). The
      freedom from structural valve deterioration was greater for advancing age groups
      (p < 0.05); AVR > or = 70 years 96% at 12 years, and 65 to 69 years 94% at 12
      years and 82% at 15 years; MVR > or = 70 years 85% at 12 years, and 65 to 69
      years 54% at 12 years. The freedom from valve-related mortality was 73% at 17
      years: AVR, 80%; ; MVR, 61%; and MR, 67% (p < 0.05 AVR > MVR, MR). The freedom
      valve-related residual morbidity was 94% (p = not significant by valve position).
      CONCLUSIONS: The Carpentier-Edwards standard porcine bioprosthesis continues to
      provide satisfactory clinical performance to 17 years. Thromboembolism is a more
      serious problem than structural failure: 92 major thromboembolic events with 41
      fatalities compared with 44 fatalities of which 33 occurred with reoperation. The
      prosthesis is especially recommended for patients more than 65 years of age for
      AVR and more than 70 years of age for MVR.

PMID- 7575008
TI  - [Multifactor analysis of ciprofloxacin action on the content of various classes
      of antibodies to EV vaccine fraction 1 and hemagglutinins].
AB  - The action of ciprofloxacin on the content of antibodies of the IgG, IgM and IgA
      classes in the blood serum of mice immunized by the EV vaccine fraction 1 as well
      as on the content of hemagglutinins to sheep erythrocytes was studied in a
      multifactor analysis with the use of a wide variety of the doses and
      administration times. In the doses corresponding to the average therapeutic ones
      ciprofloxacin increased the content of the antibody classes and especially that
      of IgG. When administered prior to the immunization the antibiotic stimulated the
      production of the hemagglutinins.

PMID- 7575009
TI  - [Multifactor analysis of the action of norfloxacin on the humoral immune
      response].
AB  - Multifactor analysis of the norfloxacin action on the primary immune response to
      the bacterial antigen (EV vaccine fraction 1) and cellular antigen (sheep
      erythrocytes) in mice was carried out with using a wide variety of the doses and
      administration times. In the doses corresponding to the average therapeutic ones
      norfloxacin was shown to have no effect on the humoral immune response to the
      bacterial and cellular antigens. In the subtherapeutic doses norfloxacin
      increased it thus mainly stimulating the synthesis of the IgM antibodies. In the
      doses exceeding the therapeutic ones the antibiotic lowered the antibody content.
      The diverse type immunoregulatory action of norfloxacin on the content of the IgG
      and IGM antibodies could be useful in the rational choice of fluoroquinolones for
      the treatment of patients with selective deficiency of immunoglobulins of various
      classes.

PMID- 7575010
TI  - [Comparative in vitro activity of ampicillin, cefoperazone, their combinations
      with sulbactam and other antibiotics with respect to staphylococci and
      pneumococci].
AB  - Antibiotic susceptibility of 225 Staphylococcus strains and 42 Pneumococcus
      strains was assayed with the method of serial microdilutions. Methicillin
      resistant Staphylococcus strains (S. aureus and coagulase negative strains) were
      characterized by high susceptibility to cephalosporins and ampicillin + sulbactam
      combination, as well as to ciprofloxacin, rifampicin and vancomycin (70 to 100
      per cent of the susceptible strains). Less than 50 per cent of the strains was
      susceptible to erythromycin. The methicillin resistant Staphylococcus strains
      preserved their high susceptibility to vancomycin and rifampicin (the coagulase
      negative strains also preserved their susceptibility to ciprofloxacin). Four
      Pneumococcus strains with the intermediate resistance to benzylpenicillin were
      isolated (for 9.6 per cent of the strains the MIC was 0.12 to 1.0 micrograms/ml).
      The growth of 2 out of these 4 strains was inhibited by the ampicillin +
      sulbactam combination in a concentration of less than 0.5 micrograms/ml and by
      cefotaxime and the cefoperazone + sulbactam combination in a concentration of
      less than 1.0 micrograms/ml. The growth of the other 2 strains was inhibited by
      betalactams in concentrations higher than the above mentioned.

PMID- 7575011
TI  - [Plasmids of antibiotic-resistant strains of Salmonella of varying origin,
      circulating the Saint-Petersburg and Leningrad region].
AB  - Two hundred and twenty Salmonella strains of various serovars isolated from
      different source in St. Petersburg and the Leningrad Region in 1984-1991 were
      investigated. It was shown that drug resistance in 39.3 per cent of the strains
      was determined by conjugative R plasmids with the molecular weights of 28 to 90
      mD which transferred at a rate of 10(-4) to 10(-8). Thirteen detected types of
      the Salmonella conjugative R plasmids differing in the resistance markers,
      molecular weights and conjugative transfer rates most frequently contained the
      genes responsible for the resistance to tetracycline (97.7 per cent),
      chloramphenicol (92.0 per cent), streptomycin (83.0 per cent), kanamycin (76.1
      per cent), monomycin (76.1 per cent) and neomycin (76.1 per cent). The
      conjugative R plasmids were mainly detected in S> typhimurium (92.9 per cent),
      especially in the isolates from humans (97.6 per cent). The most frequent plasmid
      type in the Salmonella strains of this serovar was that with the molecular weight
      of 90 mD carrying the genes of resistance to chloramphenicol, tetracycline,
      streptomycin, kanamycin, monomycin and neomycin.

PMID- 7575012
TI  - [Kinetics of 7-aminocephalosporanic acid in aqueous solutions].
AB  - Stability of 7-aminocephalosporanic acid (7-ACA) and desacetyl-7-ACA in aqueous
      solutions at the pH value higher than 6 and wide ranges of the temperature was
      studied. The kinetic parameters of the hydrolysis of the ester link in the
      molecule of 7-ACA and the openings of the betalactam link in the molecules of 7
      ACA and desacetyl-7-ACA were estimated. It was shown that all the destruction
      processes were describable by the 1st order equations. A procedure for the
      calculation of the velocity constants of the above mentioned three processes by
      changes in the concentration of 7-ACA and desacetyl-7-ACA in the solutions is
      described.

PMID- 7575013
TI  - [Sensitivity to antibacterial drugs of Salmonella isolated from various sources
      in Saint-Petersburg and Leningrad region].
AB  - The position of antibiotic resistant cultures among 1706 strains of 85 Salmonella
      serovars isolated from various sources in St. Petersburg and the Leningrad Region
      in 1984-1991 amounted to 16.4 per cent. The highest position of such cultures was
      among the isolates from humans (20.9 per cent). The positions of the isolates
      from animals, birds and environment were practically equal (13.8, 13.8 and 13.7
      per cent respectively). Strains resistant to streptomycin (11.9 per cent),
      tetracycline (11.5 per cent) and chloramphenicol (11.2 per cent) were the most
      frequent Salmonella isolates from the different sources. Rifampicin, amikacin,
      thienamycin, nitroxolin, oxolinic acid, dioxidin, ciprofloxacin and pefloxacin
      proved to be highly active against the isolates. No significant difference in the
      antibiotic resistance spectra of the Salmonella strains circulating in different
      biotopes was detected. However, among the Salmonella isolates from humans there
      undoubtedly predominated polyresistant strains with the resistance spectra
      including 10 and 6 antibacterial drugs (42.4 and 28.8 per cent of the resistant
      strains respectively). Sometimes there was observed correlation between the
      serovars of the Salmonella strains (independent of the isolation source) and the
      most characteristic spectra of their antibiotic resistance. Thus, the antibiotic
      resistant spectra of 79 per cent of the S. typhimurium strains and 82.5 per cent
      of the S. haifa strains resistant to one and more antibacterial drugs were the
      following: CmTcSmKmMmNm and ApCbCmTcSmKmMmNmGmNal respectively.

PMID- 7575014
TI  - [Effect of various pyrimidine derivatives on the effectiveness of levomycetin
      treatment of experimental infections in animals].
AB  - The experiments on mice showed that some derivatives of pyrimidine i.e. 2-methyl
      6-amino-6-oxypyrimidine and oxymisin increased the levomycetin efficacy in the
      treatment of experimental infections. The effect of 2-methyl-6-amino-6
      oxypyrimidine proved to be higher in comparison to that of oxymethyluracil.

PMID- 7575015
TI  - [Lomefloxacin pharmacokinetics in patients in the terminal stage of chronic renal
      insufficiency, undergoing treatment with programmed hemodialysis].
AB  - The most frequent complications in patients with the terminal stage of chronic
      renal insufficiency are infections of various severity. The problem of the
      antibacterial therapy choice is especially urgent because of a high frequency of
      antibiotic resistant strains and the necessity to correct the treatment regimens
      in regard to the severity of the renal failure. The pharmacokinetics of
      lomefloxacin, a new fluoroquinolone, was studied in the treatment of patients
      with the terminal stage of chronic renal insufficiency treated by programmed
      hemodialysis. Lomefloxacin was administered orally in a dose of 400 mg at an
      interval of 48 hours 24 hours prior to the hemodialysis application. There was
      observed a decrease in the maximum serum concentration of the drug by comparison
      to that in healthy persons which could be due to slow absorption of the drug and
      hyperhydration in the patients because of anuria. In the treatment of such
      patients it is necessary to provide high serum concentrations of lomefloxacin
      attainable by using higher single doses of the drug.

PMID- 7575017
TI  - [Problems of secondary microbial metabolism as discussed at an international
      scientific conference at Interlakin (Switzerland)].

PMID- 7575016
TI  - [Possible role of threonine metabolism in tetracycline biosynthesis].
AB  - The review presents the data on the metabolism of threonine and branched amino
      acids in actinomycetes. The data substantiate the hypothesis on the catabolism of
      carbohydrates through oxaloacetate--aspartate--threonine--ketomethyl valerate as
      an alternative pathway in the formation of acetyl-coA in the cells of
      tetracycline-producing cultures.

PMID- 7575018
TI  - [The diagnostic problem of cardiac myxoma].

PMID- 7575019
TI  - [A morphological study of 23 hearts with Ebstein's anomaly].
AB  - The literature published of the Ebstein anomaly of the tricuspid valve have been
      given little attention to the study of the trabecular portion of the right
      ventricle. This motivate us to study the morphology of twenty-three hearts by the
      segmentary sequential method determining with special interest the extension and
      grade of valvular attachment, dysplasia, characteristics of the trabecular
      portion of the right ventricle and associated anomalies. The three valves had
      some grade of attachment but this was less frequently in the anterior valve.
      However in our material this occurred in 43% which is consider high comparing
      with the rest of the literature; the trabecular portion had several bands at this
      zone and it was covered by the valve attachment. The downward displacement of the
      functional ring was directly proportional to the valve attachment. The structural
      anomalies of the right ventricle related to the valve malformation lead us to
      consider that the primary damage that causes this cardiopathy occurred at the
      right ventricle during the embryonic development altering the morphogenesis of
      the tricuspid valve.

PMID- 7575020
TI  - [Transtelephonic electrocardiography in Mexico. A report of the first 3434
      cases].
AB  - The transtelephonic electrocardiographic system started in the 70's and it was
      used mainly in the study of heart disease, cardiac arrhythmias, syncope and
      sudden death. This report, include 3434 electrocardiogram (ECG) of patients whom
      visit the emergency room at the General Hospital and private clinic, using three
      different forms of transtelephonic monitors. The total population were 1715 males
      and 1719 females with average age of 52.2 +/- 28.8 years. 26.9% had was present
      in history of systemic hypertension, non-insulin dependent diabetes 12.3% and
      myocardial ischemic disease in 5.3%. The main ECG indications were chest pain
      38.7%, most of them atypical angina, palpitations in 6.9% and dyspnea in 6.5%.
      50.1% of the ECG were abnormal. The most important diagnosis were:
      tachyarrhythmias (25.2%), intraventricular conduction abnormalities (17.7%),
      myocardial ischemic disease (16%), and premature ventricular and supraventricular
      beats (11.6%). We concluded that the transtelephonic electrocardiographic system
      is a very useful method, and available now in Mexico. We detected a high
      percentage of electrocardiographic abnormalities, it was possible to give the
      right diagnosis of arrhythmias, acute myocardial infarction, old infarction, and
      to evaluate the pacemaker functionality. Finally, it helped to get in brief time
      the diagnosis and treatment in cases of acute myocardial infarction or severe
      arrhythmias.

PMID- 7575021
TI  - [The mechanism of remodelling in left ventricular volume overload].
AB  - We studied 60 people who were separated into three groups. Group A: 11 patients
      with pure, severe mitral regurgitation (MR); Group B: 18 patients with pure,
      severe aortic regurgitation (AR) [this group was divided into two: I) with normal
      ejection fraction (EF) and II) with low EF]. The third group was a control one
      with 31 healthy people. Through 2-D Echocardiography (2-D Echo) we got: diameters
      of the cavities, thickness of the wall, ventricular function, h/r ratio, and
      systolic wall stress (S). Patients with MR showed left atrial and ventricular
      enlargement with low h/r ratio, normal ventricular function and raised S. The
      group I of AR had left ventricular enlargement and hypertrophy, with normal h/r
      ratio and EF, and with raised S, while the group II of AR showed left ventricular
      enlargement, low h/r ratio and EF with very high S. In MR volumetric overload
      causes different anatomic and functional changes on the left ventricle than in
      the AR. In MR there is a systolic leak toward left atrium. This causes the low S
      in the beginning of the illness and is not the mechanism that trigger left
      ventricular hypertrophy (LVH). The absence of LVH causes excessive enlargement of
      the myofibril and with time there is structural damage and contractile failure
      which raises the systolic volume and S. Later on, hypertrophy develops. On the
      other hand, since the beginning AR has high S which causes adequate hypertrophy
      (normal h/r ratio) and later it produces huge ventricular enlargement decreases
      the h/r ratio (inadequate hypertrophy) with contractile failure. We conclude: the
      time of surgery in MR is when the patient raises S and in the AR when inadequate
      hypertrophy appears (low h/r) but when EF is still normal.

PMID- 7575022
TI  - [Lipid and lipoprotein levels in athletes in different sports disciplines].
AB  - The purpose of this study was to investigate the effects of long-term high level
      physical exertion on plasma lipids and lipoproteins. Ninety-one young athletes,
      70 men and 21 women, who practiced sports such as running, swimming, rowing,
      boxing and soccer, were studied. The control group included 101 healthy subjects,
      77 men and 24 women, with sedentary life style. The mean plasma levels of total
      cholesterol (TC) (p = 0.04), low-density lipoprotein cholesterol (LDL-C) (p =
      0.04) and the atherogenic index (p = 0.01) were lower, and high-density
      lipoprotein cholesterol (HDL-C) (p < 0.005) significantly higher in male athletes
      than in controls. Mean plasma lipids and lipoproteins concentrations were not
      significantly different in sportswomen when compared with their controls. The
      prevalence of hypercholesterolemia, hypertriglyceridemia and low HDL-C levels,
      were lower in male and female athletes of the five sport disciplines than in
      sedentary controls; however, only hypercholesterolemia (p < 0.05) and the
      atherogenic index (p < 0.01) were statistically different. These results,
      consistent with data previously published, show that low plasma levels of TG and
      high levels of HDL-C characterizes the athletes who practice an aerobic physical
      activity; additionally, in male athletes we found that long-term exercise appears
      to reduce LDL-C plasma levels. This latter finding agree with most, but not all,
      studies in the literature. We conclude that athletes have a lipid profile that
      may be protective against the development of atherosclerosis.

PMID- 7575023
TI  - [Percutaneous transluminal angioplasty with a balloon catheter in native aortic
      coarctation: long-term experience].
AB  - Between August 1988 and October 1993, 19 patients with native aortic coarctation
      were subjected to transluminal percutaneous balloon angioplasty, 12 of which were
      men (63.1%) and 7 were women (36.9%), with an average age of 22 +/- 7.7 years (r-
      16 to 52), all of whom suffered from arterial hypertension at the time of the
      procedure, and a systolic pressure of 190 +/- 32.2 mmHg (r- 160 to 240). The
      gradient of the systolic pressure (GPS) was 77 +/- 0.9 mm, the average diameter
      of the balloon catheters that were used was 18.3 +/- 1.7 mm (r- 15 to 20). For
      all the patients, the procedure was carried out under local anesthesia and the
      usual Seldinger technique. After carrying out the procedure, the GPS as well as
      the blood pressure dropped to 5.0 +/- 4.1 mmHg and 130 +/- 20.6 mmHg,
      respectively. In similar manner, the enlargement of the ring displayed an
      increase of 4.2 +/- 0.9 to 14.1 +/- 1.6 mm. There were no complications in any of
      the procedures. During the follow-up, 11 patients were catheterized again in a
      period of 24.7 +/- 12.6 months (r- 10 to 48) with GPS of 5 +/- 2 mmHg. Besides,
      an increase of 15.4 +/- 1.2 mm in the ring's diameter was observed. In these
      patients, there was no evidence of the aneurysms at the dilatation site. Of the
      rest of the patients under control, 17 of whom have been able to maintain normal
      blood pressure without medical treatment, and only two required low dosages of
      antihypertensive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575024
TI  - [Auricular flutter associated with an interatrial septal aneurysm submitted to
      radiofrequency ablation].
AB  - We present the case of a young man who began with type I atrial flutter, he had
      no response to antiarrhythmic drugs. The echocardiogram showed an atrial septal
      aneurysm in the region of the fossa ovalis. We performed an electrophysiologic
      study which showed an atrial flutter with atrial rate of 257 bpm, and 2:1/3:1 AV
      conduction. The flutter waves were negatives in leads II, III and a VF (type I
      atrial flutter). An endocardial mapping was obtained in order to localize the
      area of slow conduction. It was located in the isthmus of atrial tissue bounded
      by the inferior vena cava and the tricuspid valve annulus in the low posterior
      septal right atrium. In this area we applied radiofrequency energy in 10
      occasions but the arrhythmia was not suppressed. With atrial pacing we achieve a
      concealed entrainment and then resumption of atrial flutter after cessation of
      pacing. After another 6 applications of radiofrequency in this same area in sinus
      rhythm, we paced the atrium without inducing any form of arrhythmia. He was
      asymptomatic 15 days later, but one month after the ablation, the flutter
      reappeared, we performed a second successful radiofrequency ablation. In this
      time he was asymptomatic.

PMID- 7575025
TI  - [Percutaneous transluminal angioplasty of the vena cava inferior].
AB  - We describe a 65-years-old female, with percutaneous balloon angioplasty (PBA) of
      inferior vena cava. The patient had massive calcification of the right atrium,
      the tricuspid anulus as well as obstruction of the tricuspid valve (percutaneous
      tricuspid valvuloplasty was performed 2.5 years before). The only predisposing
      factor for calcification was, a cerebral-right atrial shunt (cerebral
      cysticercosis) for 32 years. PBA was performed. We discuss some events that
      occurred after dilatation. We describe the technique in this uncommon case. We
      conclude that percutaneous balloon angioplasty is another alternative to surgical
      repair in inferior vena cava obstruction.

PMID- 7575026
TI  - [Percutaneous mitral commissurotomy with an Inoue catheter in congenital mitral
      stenosis].
AB  - We describe a 3-years-old boy, with congenital mitral stenosis, who underwent
      percutaneous transvenous mitral commissurotomy (PTMC) with Inoue balloon. The
      mitral gradient decreased from 24 to 4 mmHg, the mitral valvular area (MVA)
      increased from 1.2 to 1.6 cm2 without modification in mitral regurgitation. One
      year later the recatheterization showed decreased pulmonary pressures, and a 7.5
      mmHg mitral valvular gradient without mitral insufficiency. MVA by echo is 1.8
      cm2 with mild regurgitation. As far as we know there is no experience with Inoue
      balloon in children. We conclude that PTMC with Inoue balloon could be an
      attractive alternative in some patients with congenital mitral stenosis.

PMID- 7575027
TI  - [Mitral subvalvular aneurysm of probable chagasic etiology].
AB  - The case report is a woman 45 years old from a rural zone of the Federal District
      (Mexico City) with subvalvular mitral aneurysm of probable chagasic origin. Its
      main clinic manifestation was caused by the presence of recurrent ventricular
      arrhythmias refractory to medical treatment. The diagnosis was made by means of
      the serology, echocardiography, cineangiography and endocardial biopsy. The
      treatment consisted in the surgical resection of the aneurysm with successful
      evolution.

PMID- 7575028
TI  - [The electrophysiological approach to the diagnosis of right ventricular
      enlargement].

PMID- 7575030
TI  - [Study of 3985 female genital smears from the Clinical Biology Center of the
      Pasteur Institute in Madagascar].
AB  - A microbiological study of 3985 cervico-vaginal swabs has been carried out on
      patients from Pasteur Institute of Madagascar, most of them suffering from
      leucorrhea. This puts forward the predominance of non-specific vaginitis as well
      as cervicitis caused by mycoplasmas.

PMID- 7575029
TI  - [Hepatic hydatidosis in Madagascar: a case of autochthonous origin].
AB  - Hydatid disease, due to the larval stage of Echinococcus granulosus, is described
      for the second time at liver level, in Madagascar. Even with a low level of
      endemic animal disease and an uncontrolled population of stray dogs, the human
      parasitosis is very rare in Madagascar. It is interesting to note that, since a
      hundred of years, the epidemiological status of this Zoonosis has not really
      changed in the great island.

PMID- 7575031
TI  - [Cholelithiasis in the south of Madagascar (47 cases)].
AB  - 47 cases (14 men and 33 women) of cholelithiasis were described in a southern
      district of Madagascar. Ultrasonography was used for diagnosis. In most cases,
      calculi were numerous. In this study, risk factors correlated with cholelithiasis
      were not found.

PMID- 7575032
TI  - [Renal glomerular lesions and Plasmodium falciparum infection].
AB  - Following the study done in 1990 concerning the existence of glomerular lesions
      in falciparum malaria, this study, pursued on large scale, included 110 persons
      (30 healthy persons, 11 other than falciparum malaria, and 69 cases of falciparum
      malaria). 30.4% among these 69 cases of falciparum malaria presented glomerular
      affect signs. A complete clinical and biological recovery was obtained with
      quinine injection.

PMID- 7575033
TI  - [Results of 466 nerve decompressions in 123 leprosy patients during
      polychemotherapy with a minimum follow-up of one year. Value of preventive
      surgery in a leprosy control program].
AB  - The clinical expression of leprosy is primarily cutaneous but its serious
      neurologic manifestations are maiming. Mutilations mainly of limb ends are due to
      peripheric nerves compression and may appear before or during the clinical
      treatment of the illness. Their appearance which is not automatically related to
      multiple Hansen's bacilli, may be prevented surgically by nervous decompression.
      The authors report their experiences of 466 nervous decompressions of 123
      patients (89 men and 34 women), among them, 14 were pauci-bacillary and 109 multi
      bacillary. They conclude that very good results (complete recovery or improvement
      of sensitivity, disappearing of pain) have been obtained through simple and easy
      to-learn surgeries.

PMID- 7575034
TI  - [In situ dissolution of uric acid obstructive calculi].
AB  - The dissolution of uric acid calculi can be obtained by per os or parenteral
      alkalinization, but this method cannot be used in case of obstructive calculi.
      With 3 patients, whose urinary tract was obstructed by a radio-transparent
      calculi at the pyelo-ureteral junction, the ureteral probe setting by endoscopic
      way permitted to realize the in situ alkalinization. After 5 to 11 days of
      treatment, the calculi have been completely dissolved. A patient also presented a
      slightly radio-opaque lithiasis, but it remained still. The in situ
      alkalinization is an effective and non invasive treatment in case of obstructive
      uric acid calculi, and completes the release of the urinary tract logically by
      ureteral probe setting.

PMID- 7575035
TI  - [Madagascar snakes: preliminary note on new species of Stenophis Boulenger genus,
      1896. (Colubridae-Boiginae)].
AB  - The author suggests to rehabilitate the genus Stenophis united since 1958 with
      the genus Lycodryas. This rehabilitation is justified by the differences that
      exist between malagasy and comorian species of snake, gathered within the genus
      Lycodryas. In this genus Stenophis, he distinguishes 3 sub-genera: Stenophis
      Boulenger, Phisalixella and Parastenophis. Then he describes 8 new species
      belonging to the genus Stenophis.

PMID- 7575036
TI  - [A malaria epidemic in the south of Madagascar?].
AB  - Authors record the results of entomological and paludometric studies which were
      run on July 1994 in Ampanihy (Southern Madagascar), since an epidemic of malaria
      occurred in that region. Although the risk of epidemic malaria is described in
      the Southern Madagascar, paludometric indexes found in these surveys are
      pertinent with a mesoendemic malaria. The entomological survey found. A gambiae
      complex and A. funestus. Complementary surveys are proposed to improve the
      knowledge of the epidemiology of malaria in this area.

PMID- 7575037
TI  - [Study of malaria vectors in the south-west of Madagascar].
AB  - The authors describe the results of an entomological study run in December 1994
      in the little town of Bezaha (South-Western Madagascar). The observed
      entomological indexes are those of an intensive malaria transmission area. The
      authors suggest to organize a longitudinal entomological survey along with a
      clinical and parasitological study. They also point out the fact that they found
      two microfilariae Wuchereria bancrofti in an Anopheles funestus female.

PMID- 7575039
TI  - [Twenty eight cases of ichthyosarcotoxism in children in Madagascar (Toliara)].
AB  - Each year from November to April, cases of fish poisoning are reported with
      variable incidences according to villages disseminated along malagasy coasts.
      Occasional mass poisonings are often mentioned but precise clinical signs are not
      described nor published. Several fishes are responsible for these poisonings but
      only four kinds are often mentioned: shark, tuna, sardine and mackerel. Among
      children, digestive, cutaneous and neurological signs predominate in a specially
      polymorphic ciguatoxin clinical schedule. The importance of cardio-vascular or
      respiratory diseases or high fever may compromise the life prognosis. In the
      main, the evolution is good after one week. In Toliara hospital, only symptomatic
      therapy is applied.

PMID- 7575040
TI  - [Fatal ichthyosarcotoxism after eating shark meat. Implications of two new marine
      toxins].
AB  - A fish poisoning involving 188 hospitalizations occurred in November 1993, in
      Manakara, a middle-sized town on the south-east coast of Madagascar, following
      the ingestion of shark. A single shark was involved in this poisoning and was
      identified as Carcharinus leucas. There was no unusual characteristic of this
      shark or its meat. The attack rate was about 100%. First clinical signs appeared
      within five to ten hours after ingestion. The patients presented neurological
      symptoms almost exclusively, the most prominent being a constant, severe ataxia.
      Gastrointestinal troubles, like diarrhoea and vomiting were rare. The overall
      case-fatality ratio was close to 30% among the 200 poisoned inhabitants. Search
      for similar poisoning previously reported in this area was negative, and
      fishermen in Manakara usually eat that kind of shark without mistrust.
      Bacteriological and chemical origins were eliminated. Two liposoluble toxins were
      isolated from the shark liver and tentatively named carchatoxin-A and -B
      respectively. They were distinct from ciguatoxin in chromatographic properties.

PMID- 7575038
TI  - [HIV infection in tuberculosis patients in Madagascar. Situation in 1-93].
AB  - In Madagascar, the estimated incidence of tuberculosis is high (320 per 100,000)
      when human immunodeficiency virus (VIH) infection progress slowly. The authors
      have studied HIV seroprevalence in a group of tubercular patients and in two
      reference groups (general population and outpatients of the Clinical Biology
      Centre of Institut Pasteur). Circulation of HIV1 virus was observed with a low
      prevalence rate in all the 3 groups. There was no significant difference between
      tubercular patients and healthy population. Tubercular people ought to be a watch
      group for the epidemiological surveillance of HIV infection evolution in
      Madagascar.

PMID- 7575041
TI  - [Mass food poisoning after eating sea turtle in the Antalaha district].
AB  - In December 1994, a mass food poisoning through ingestion of turtle affected
      about 60 persons, on the north-eastern coast of Madagascar. The prevailing
      clinical signs were digestive (nausea, vomiting, dysphagia, acute stomatitis) and
      might persist during several weeks. The poisoning attack rate was 48% with a
      lethality of 7.7%. Such accident, even if rare in Madagascar, requires a
      structured organization to control sea products poisoning and to set up adequate
      prevention measures.

PMID- 7575042
TI  - [Scalp pediculosis and its treatment: bioclinical trials of different
      pediculicides and repellents in Antananarivo].
AB  - After a recall of different existing kinds of louse, pediculicides and their mode
      of action, the authors report the bio-clinical trials they carried out in
      Antananarivo using different associations and galenic forms of medicines. The
      objectives of these studies on the treatment of scalp pediculosis is either the
      development of efficient insecticides or the application for the official permit
      of sale.

PMID- 7575043
TI  - [Bacterial quality of the water supply in Madagascar].
AB  - The results of 14371 drinking water analysis carried out in Madagascar between
      1986 and 1993 by the water analysis and food microbiology laboratory of the
      Pasteur Institute of Madagascar are reported. After a history of the water
      analysis laboratory, methods and frequency of sampling, methods of analysis and
      standards applied are quoted and documented. Results for each province are
      reported and particularly indicated: the development of water samples and their
      portability along the years, the respective frequency of pollutant bacteria and
      their amounts according to sampling points. In spite of the lack of means in the
      country, the authors consider the results are satisfactory but they stress the
      importance of an organized surveillance system of drinking water quality.

PMID- 7575044
TI  - [Entomophthoromycoses in Madagascar (three cases)].
AB  - The authors present three new cases of Entomophthoromycosis observed in
      Madagascar: Two cases of subcutaneous entomophthoromycosis without isolation of
      germ. An immunofluorescence technique showed the Basidiobolus ranarum to be the
      real cause. One case of rhinoentomophthoromycosis with isolation of Conidiobolus
      coronatus (first isolation in Madagascar).

PMID- 7575045
TI  - 'Cure' of Helicobacter pylori. Clinically indicated and economically wise!

PMID- 7575046
TI  - An analysis of the effectiveness of interventions intended to help people stop
      smoking.
AB  - In a systematic review of the efficacy of interventions intended to help people
      stop smoking, data have been analyzed from 188 randomized controlled trials.
      Following personal advice and encouragement to stop smoking given by physicians
      during a single routine consultation, an estimated 2% (95% confidence limits, 1%,
      3%; P < .001) of all smokers stopped smoking and did not relapse up to 1 year as
      a direct consequence of the advice. The effect is modest but cost-effective: the
      cost of saving a life is about $1500. Supplementary interventions (follow-up
      letters or visits, demonstration of spirometry, etc) have an additional effect-
      variable in extent. Advice and encouragement are particularly effective for
      smokers at special risk--pregnant women (efficacy; 8%) and patients with ischemic
      heart disease. Behavior modification techniques (relaxation, rewards and
      punishment, avoiding "trigger" situations, etc), in group or individual sessions
      led by a psychologist, have an effect that is statistically significant (P = .05)
      but no greater than simple advice by a physician (2%); yet, these techniques are
      several times more expensive. The effect of hypnosis is unproved (no trials have
      used biochemical markers). Nicotine replacement therapy is effective in an
      estimated 13% of smokers who seek help in cessation; the effect is greater in
      those who are nicotine-dependent. Other pharmacological treatments are not of
      proven efficacy, and acupuncture is ineffective. Sudden cessation or gradual
      reduction in smoking are similar in their efficacy on average. Physicians should
      take time to advise all their patients who smoke to quit. Smokers who are intent
      on stopping should be given additional support and encouraged to use nicotine
      replacement therapy.

PMID- 7575047
TI  - Passive smoking and cardiovascular risk.
AB  - A possible relationship between passive smoking and coronary heart disease has
      been widely debated during the past decade. Convincing evidence links
      environmental (passive) tobacco smoke exposure to heart disease morbidity as well
      as mortality. In the United States, 37,000 coronary heart disease deaths per year
      are attributed to environmental tobacco smoke exposure, accounting for 70% of all
      deaths caused by environmental tobacco smoke. The analysis of 10 epidemiologic
      studies indicated a consistent dose-response effect related to exposure, but more
      proof is still needed. Evidence indicates that nonsmokers are more sensitive to
      smoke, including cardiovascular effects, and that sidestream smoke contains
      higher concentrations of gas constituents, including carbon monoxide.
      Pathophysiological and biochemical data after short- and long-term environmental
      tobacco smoke exposure show changes in endothelial and platelet function as well
      as exercise capacity similar to those in active smoking. Therefore, passive
      smoking is a relevant risk factor for heart disease morbidity and mortality.

PMID- 7575048
TI  - Drug-related morbidity and mortality. A cost-of-illness model.
AB  - BACKGROUND: Preventable drug-related morbidity and mortality represent a serious
      medical problem that urgently requires expert attention. The costs to society of
      the misuse of prescription medications, in terms of morbidity, mortality, and
      treatment, can be immense. To date, research has primarily documented increased
      rates of hospitalization secondary to medication noncompliance and/or adverse
      drug effects. OBJECTIVES: To develop a conceptual model of drug-related morbidity
      and mortality, and to estimate the associated costs in the ambulatory setting in
      the United States. METHODS: A probability pathway model was developed to estimate
      the cost of drug-related morbidity and mortality in the United States. Pharmacist
      practitioners were surveyed to determine conditional probabilities of therapeutic
      outcomes owing to drug therapy. Health care utilization and associated costs
      owing to negative therapeutic outcomes were estimated. RESULTS: Drug-related
      morbidity and mortality was estimated to cost $76.6 billion in the ambulatory
      setting in the United States. The largest component of this total cost was
      associated with drug-related hospitalizations. When assumptions of the model were
      varied, the estimated cost ranged from a conservative estimate of $30.1 to $136.8
      billion in a worst-case scenario. CONCLUSIONS: The cost of drug-related morbidity
      and mortality in the ambulatory setting in the United States is considerable and
      should be considered in health policy decisions with regard to pharmaceutical
      benefits. Policies and services should be developed to reduce and prevent drug
      related morbidity and mortality.

PMID- 7575049
TI  - Cost-effectiveness of Helicobacter pylori eradication for the long-term
      management of duodenal ulcer in Canada.
AB  - BACKGROUND: A 1994 National Institutes of Health consensus panel recommended that
      eradication of Helicobacter pylori should be first-line therapy for persons with
      duodenal ulcer. OBJECTIVE: To assess the cost-effectiveness of H pylori
      eradication relative to alternative pharmacologic strategies in the long-term
      management of persons with confirmed duodenal ulcer. METHODS: Decision analysis
      model to estimate expected costs and symptomatic ulcer recurrences during a 12
      month period for three general treatment strategies: (1) immediate H pylori
      eradication; (2) H pylori eradication at first ulcer recurrence; and (3)
      continuous maintenance therapy with a histamine2 receptor antagonist (ranitidine
      hydrochloride). Two H pylori eradication therapies were compared: classic triple
      therapy and omeprazole plus amoxicillin. Probabilities for ulcer recurrence are
      by meta-analysis of published randomized trials. Health care resources used in
      the management of duodenal ulcer recurrence were by expert physician panel. All
      costs are in 1993 Canadian dollars. RESULTS: Duodenal ulcer recurrence at 6
      months (symptomatic and asymptomatic) with placebo was 65.4% and 12.8% with
      maintenance ranitidine therapy. Where eradication of H pylori was successful (85%
      of patients), the ulcer recurrence rate to 12 months was 3.7%. Treatment with
      ranitidine and triple therapy to eradicate H pylori on first presentation has an
      expected 1-year cost of $253 with 15 symptomatic recurrences per 100 patients; H
      pylori eradication by omeprazole plus amoxicillin had similar expected costs
      ($272) and outcomes (15 recurrences per 100 patients). Both of these early H
      pylori eradication strategies were dominant (less costly with same or better
      outcomes) over intermittent or continuous maintenance ranitidine therapy or
      delayed (after first recurrence) H pylori eradication. CONCLUSION: Our analysis
      provides economic evidence in support of the recent guidance that for persons
      with duodenal ulcer, early attempts to eradicate H pylori are recommended.

PMID- 7575050
TI  - Neutropenia and bacterial infection in acquired immunodeficiency syndrome.
AB  - BACKGROUND: In human immunodeficiency virus (HIV) disease, neutropenia occurs
      most commonly in patients who are also severely immunosuppressed. It is not
      currently known whether neutropenia is an independent risk factor for the
      development of bacterial infection, which is a potentially serious complication
      of advanced HIV disease. METHODS: We compared the incidence of bacterial
      infection between 118 neutropenic patients (absolute neutrophil count [ANC], < 1
      x 10(9)/L) and 118 nonneutropenic patients matched for CD4+ lymphocyte count, use
      of injecting drugs, and follow-up time from a demographically heterogeneous urban
      cohort of HIV-infected patients followed up longitudinally at the Johns Hopkins
      Hospital. The incidence of serious infection was analyzed separately for patients
      with an ANC of less than 1, less than 0.75, or less than 0.5 x 10(9)/L. RESULTS:
      There were no statistically significant associations found between neutropenia
      and several individual bacterial infections, including bacteremia, pneumonia,
      endocarditis, bacterial enterocolitis, and infection of normally sterile sites
      for any level of neutropenia. However, for all these infections combined, the
      adjusted relative risk for the occurrence of bacterial infection was 2.33 (95%
      confidence interval, 1.00 to 5.40; P = .05) for patients with an ANC of less than
      1 x 10(9)/L and 7.92 (95% confidence interval, 1.18 to 53.2; P = .03) for those
      with an ANC of less than 0.5 x 10(9)/L. The incidence of serious bacterial
      infection ranged from two to three infections per 100 person-months of
      neutropenia for patients with an ANC of less than 1 x 10(9)/L and three to five
      infections per 100 person-months of neutropenia for patients with an ANC of less
      than 0.5 x 10(9)/L for all bacterial infections combined. CONCLUSIONS: Our
      matched cohort analysis indicates that neutropenia is an independent risk factor
      for bacterial infection in patients with advanced HIV disease. Given the
      incidence of infection, the cost-effectiveness of interventions to prevent
      neutropenia in advanced HIV disease should be assessed.

PMID- 7575051
TI  - Effectiveness of the 4-mg dose of nicotine polacrilex for the initial treatment
      of high-dependent smokers.
AB  - PURPOSE: To determine the effectiveness of the 4-mg and 2-mg dosages of nicotine
      polacrilex vs placebo through the first 6 weeks of treatment (during which 75% of
      relapse occurs when there is no treatment) in assisting high-dependent smokers to
      stop smoking when instructed to use a fixed number (12 pieces) of medication
      daily. SUBJECTS AND METHODS: Ninety high-dependent (Fagerstrom Tolerance
      Questionnaire score > or = 7 plus baseline carbon monoxide level > 15 ppm)
      healthy male and female smokers, highly motivated to quit smoking, were enrolled
      in a 6-week, randomized, double-blind, placebo-controlled trial in which they
      were instructed to use 12 pieces per day of their assigned dosage formulation: 4
      mg, 2 mg, or 0.5 mg (placebo) of nicotine polacrilex. The behavioral intervention
      did not depend on providing any special psychological training, skills, or
      services but rather employed a standard medical practice model that could easily
      be implemented by any primary care physician. RESULTS: Sustained abstinence from
      weeks 2 through 6, determined at each visit by absolutely no cigarette use plus a
      carbon monoxide level of 8 ppm or lower was 59% (4-mg group), 30% (2-mg group),
      and 39% (placebo group) (P < .02). For the 55 of the 90 smokers who met the
      originally planned definition of high dependence (Fagerstrom Tolerance
      Questionnaire score > or = 7 plus baseline smoking serum cotinine level > 250
      ng/mL plus baseline carbon monoxide level > 15 ppm), results were 63% (4-mg
      group), 25% (2-mg group), and 25% (placebo group) (P < .02). In addition, the 4
      mg dose produced statistically significantly higher abstinence rates in compliant
      subjects (P < .02) and also in subjects with high baseline serum continine levels
      who were compliant (P < .01) than did either the 2-mg dose or placebo.
      CONCLUSIONS: It appears that the 4-mg dose of nicotine polacrilex is the drug and
      dose of choice for the initial phase of tobacco dependence treatment in high
      dependent smokers; the 2-mg dose of nicotine polacrilex is not better than
      placebo during the first 6 weeks of treatment for high-dependent cigarette
      smokers, and thus should not be used for these patients during the initial
      treatment phase.

PMID- 7575052
TI  - Is the course of neurocysticercosis modified by treatment with antihelminthic
      agents?
AB  - BACKGROUND: Neurocysticercosis, occasionally associated with long-term neurologic
      sequelae such as epilepsy or hydrocephalus, is more often a condition
      characterized by a benign course and spontaneous remission without permanent
      neurologic symptoms. This variability in outcome has led to difficulties in the
      interpretation of studies of the effectiveness of drugs used to treat this
      condition. OBJECTIVE: To evaluate the relative efficacy of two antihelminthic
      agents against each other and against symptomatic treatment alone. METHODS:
      Randomized clinical trial of treatment of patients with newly identified active
      neurocysticercosis with oral prednisolone alone (27 patients), praziquantel with
      prednisolone (54 patients), or albendazole with prednisolone (57 patients).
      RESULTS: At 6 months and at 1 year after treatment, there were no differences in
      the three treatment groups in terms of the proportion of patients who were free
      of cysts or the relative reduction of number of cysts. At 2 years, there was no
      difference in the proportion of patients free of seizures during the entire
      follow-up period. Early and late sequelae occurred in a higher proportion of
      patients treated with praziquantel and albendazole, compared with those receiving
      only prednisolone. CONCLUSIONS: Previous reports of favorable response to
      treatment of neurocysticercosis with either praziquantel or albendazole are by no
      means definitive and may be a reflection of the natural history of the condition.
      The present study, with randomized treatment assignment and including a control
      group, raises questions as to what extent and in whom treatment with these drugs
      is effective, and suggests that treatment with antihelminthic agents may be
      associated with an increased frequency of long-term sequelae.

PMID- 7575053
TI  - Utility of scintigraphic methods in patients with fever of unknown origin.
AB  - BACKGROUND: We assessed the utility of scintigraphy with indium 111-labeled
      polyclonal human IgG scintigraphy in patients with fever of unknown origin that
      fulfilled the criteria of temperature of 38.3 degrees C or more for at least 3
      weeks and no diagnosis during 1 week of hospital admission. We compared the
      utility of this technique with results of scintigraphic techniques reported in
      the literature. METHODS: Data for all patients seen at our university hospital in
      whom 111In-IgG scanning was performed were analyzed and checked for the criteria
      for fever of unknown origin. The literature on the utility of scintigraphic
      techniques in patients with fever of unknown origin was reviewed. RESULTS: We
      studied 24 patients with fever of unknown origin. In 13 patients, focal 111In-IgG
      accumulation was observed. In nine (38%) of those, the positive 111In-IgG
      scintigram led to the final diagnosis; in the other four patients (17%), the
      scintigraphic findings were not helpful. In the 11 patients with negative 111In
      IgG scans, extensive diagnostic workup produced no infection as the final
      diagnosis in nine patients (38%), one had an abscess in a renal cyst that was
      detected several months later, and in the other the cause of fever was an
      infected intravenous line. The overall sensitivity and specificity of 111In-IgG
      scintigraphy were 81% and 69%, respectively. The positive predictive value was
      69% and the negative predictive value was 82%. CONCLUSIONS: Our results show that
      111In-IgG scintigraphy significantly contributed to the diagnostic process in
      patients with fever of unknown origin. A positive scan increased the likelihood
      of finding the cause of the fever, and a negative scan ruled out an inflammatory
      component with a high degree of certainty. These data compare favorably with data
      in the literature concerning other radiopharmaceuticals; a larger prospective
      evaluation of this technique is indicated.

PMID- 7575054
TI  - Perioperative mortality of elective abdominal aortic aneurysm surgery. A clinical
      prediction rule based on literature and individual patient data.
AB  - BACKGROUND: Abdominal aortic aneurysm surgery is a major vascular procedure with
      a considerable risk of (mainly cardiac) mortality. OBJECTIVE: To estimate
      elective perioperative mortality, we developed a clinical prediction rule based
      on several well-established risk factors: age, gender, a history of myocardial
      infarction, congestive heart failure, ischemia on the electrocardiogram,
      pulmonary impairment, and renal impairment. METHODS: Two sources of data were
      used: (1) individual patient data from 246 patients operated on at the University
      Hospital Leiden (the Netherlands) and (2) studies published in the literature
      between 1980 and 1994. The Leiden data were analyzed with univariate and
      multivariate logistic regression. Literature data were pooled with meta-analysis
      techniques. The clinical prediction rule was based on the pooled odds ratios from
      the literature, which were adapted by the regression results of the Leiden data.
      RESULTS: The strongest adverse risk factors in the literature were congestive
      heart failure and cardiac ischemia on the electrocardiogram, followed by renal
      impairment, history of myocardial infarction, pulmonary impairment, and female
      gender. The literature data further showed that a 10-year increase in age more
      than doubled surgical risk. In the Leiden data, most multivariate effects were
      smaller than the univariate effects, which is explained by the positive
      correlation between the risk factors. In the clinical prediction rule, cardiac,
      renal, and pulmonary comorbidity are the most important risk factors, while age
      per se has a moderate effect on mortality. CONCLUSIONS: A readily applicable
      clinical prediction rule can be based on the combination of literature data and
      individual patient data. The risk estimates may be useful for clinical decision
      making in individual patients.

PMID- 7575055
TI  - Thyroid hormone use and bone mineral density in elderly men.
AB  - BACKGROUND: Excessive thyroid hormone use reduces bone density in women. Thyroid
      hormone use is much less common in men, who also have less osteoporosis. We
      examined bone mineral density in a community-based sample of elderly men who
      reported long-term thyroid hormone use. METHODS: All 685 white men aged 50 to 98
      years from a Southern California community who participated in a study of
      osteoporosis were examined. Medication use was validated. Height and weight were
      measured. Bone mineral density was measured at the ultradistal radius and
      midshaft radius using single photon absorptiometry and at the hip and lumbar
      spine using dual energy x-ray absorptiometry. RESULTS: Thirty-three men taking a
      mean thyroxine-equivalent dose of 130 micrograms daily for an average of 15.5
      years were compared with 653 nonusers. There were no significant differences in
      bone density at any site between users and nonusers, before or after controlling
      for age, body mass index, smoking, thiazide diuretics, and oral corticosteroid
      use. Bone density also did not differ according to thyroid hormone type, duration
      of use, or use of suppressive dose adjusted for body weight. CONCLUSIONS: Long
      term thyroid hormone use was not associated with adverse effects on bone mineral
      density in men.

PMID- 7575056
TI  - Plummer-Vinson syndrome. A case report and literature review.
AB  - The Plummer-Vinson syndrome is characterized by dysphagia, iron-deficiency
      anemia, and esophageal webs. The webs are best diagnosed by cineradiography. Iron
      repletion often improves the dysphagia, although some patients require esophageal
      dilatation or bougienage. The syndrome is associated with an increased incidence
      of postcricoid carcinoma, and surveillance endoscopy is recommended.

PMID- 7575057
TI  - Altitude-dependent decrease in plasma fibronectin.

PMID- 7575058
TI  - Ethics and organ use.

PMID- 7575059
TI  - Start low and go slow: dosing of antipsychotic medications in elderly patients
      with dementia.

PMID- 7575060
TI  - Treating advanced cancer in an era of increasing cost consciousness.

PMID- 7575061
TI  - Significance of Africanized bees for public health. A review.
AB  - Although massive sting attacks by Africanized bees are currently rare, this type
      of bee is now endemic in parts of Arizona and Texas, and will probably spread to
      other warm climate areas in the United States. Treatment of severe toxic
      reactions to multiple stings usually includes management of shock, hypoxia, and
      other effects of organ damage. New approaches to reduce blood levels of venom
      including production of a bee antivenom and hemodialysis require further study.
      Patients with a trivial allergy to single stings could be at risk from systemic
      anaphylaxis to multiple bee sting. Those who wish to remain in endemic areas in
      spite of histories of systemic anaphylaxis to bee stings should be treated with
      venom immunotherapy, possibly administered more intensively and for longer
      periods than currently recommended. Continued public education is needed to limit
      contact with aggressive Africanized bee colonies.

PMID- 7575062
TI  - Academic health centers. Vulnerabilities in 1995 and beyond.
AB  - Resources to support biomedical research in the nation's academic health centers
      are under considerable threat. Particularly vulnerable is the clinical research
      enterprise. New strategies and prioritization will be required to maintain the
      vitality of our clinical research and education enterprise.

PMID- 7575063
TI  - The need to consider survival, outcome, and expense when evaluating and treating
      patients with unknown primary carcinoma.
AB  - BACKGROUND: Patients who present with unknown primary carcinomas represent 10% to
      15% of the patients with cancer who present to medical centers. Despite data in
      the literature indicating minimal success in determining the location of primary
      carcinomas, these patients continue to be evaluated exhaustively. Additionally,
      identification of the location of primary carcinomas does not often affect
      treatment. Clinical treatment and prognosis are only affected if a reevaluation
      of the pathologic findings yields a potentially curative diagnosis of an
      undifferentiated lymphoma, germ cell tumor, or a hormonally sensitive carcinoma.
      METHODS: Tumor registry files from January 1, 1990, through December 31, 1992,
      were retrospectively retrieved to identify adult patients who presented with
      metastasis of an unknown primary site at the H. Lee Moffitt Cancer Center and
      Research Institute, a 162-bed tertiary care cancer center specialty hospital
      affiliated with the University of South Florida College of Medicine, Tampa.
      Medical records were reviewed for age, sex, histologic findings of previous
      malignant growth, types and duration of symptoms, and mode of presentation. Fifty
      six of the 199 patients were included in the study; 31 were men (55.4%) and 25
      were women (44.6%), with ages ranging from 33 to 83 years. Diagnostic evaluations
      were reviewed and included data from procedures conducted at both the H. Lee
      Moffitt Cancer Center and at outside facilities. Diagnostic studies performed
      included barium swallow; intravenous pyelogram; mammogram; abdominal ultrasound;
      chest x-ray film; bone scan; magnetic resonance imaging; computed tomography of
      the head, chest, abdomen, and pelvis; laparotomy; bronchoscopy; gastroscopy; and
      colonoscopy. Information for the diagnostic test procedures was taken from the
      point of initial patient contact until the determination of metastatic disease.
      RESULTS: The primary cancer site was found in four (7.1%) of the 56 cases in the
      study and could not be classified as curable by systemic means. The average cost
      of diagnosis was $17,973, with 19.6% of the patients surviving for more than 1
      year. The mean survival period was 8.1 months. A total of 410 tests were
      performed with only four tests correctly identifying the location of the primary
      tumor. CONCLUSIONS: Once a potentially curable malignancy has been excluded,
      there is little justification to support extensive diagnostic evaluation of the
      patient. Substantial costs are incurred and survival is often not significantly
      affected. It was estimated that 1.2 million new cancer cases would have occurred
      during 1994, with approximately 10% of these patients presenting with cancer of
      unknown primary origin. Based on cost assessments, investigation of these
      patients would exceed $1.5 billion. This clinical scenario is one where attention
      to outcome, clinical management, and expense should be carefully considered.

PMID- 7575064
TI  - Epidemiology of do-not-resuscitate orders. Disparity by age, diagnosis, gender,
      race, and functional impairment.
AB  - BACKGROUND: The relationship of do-not-resuscitate (DNR) orders to patient and
      hospital characteristics has not been well characterized. METHODS: This
      observational study of a nationally representative sample of 14,008 Medicare
      patients hospitalized with congestive heart failure, acute myocardial infarction,
      pneumonia, cerebrovascular accident, or hip fracture evaluated the relationship
      of DNR orders to patient sickness at admission, functional impairment, age,
      disease, race, gender, preadmission residence, insurance status, and hospital
      characteristics. RESULTS: Of the 14,008 patients, DNR orders were assigned to
      11.6%. Patients with greater sickness at admission and functional impairment
      received more DNR orders (P < .001) but even among patients in the sickest
      quartile (with a 65% chance of death within 180 days), only 31% received DNR
      orders. The DNR orders were assigned more often to older patients after
      adjustment for sickness at admission and functional impairment (P < .001), and
      DNR order rates differed by diagnosis (P < .001). After adjustment for patient
      and hospital characteristics, DNR orders were assigned more often to women and
      patients with dementia or incontinence and were assigned less often to black
      patients, patients with Medicaid insurance, and patients in rural hospitals.
      CONCLUSIONS: Do-not-resuscitate orders are assigned more often to sicker patients
      but may be underused even among the most sick. Sickness at admission and
      functional impairment do not explain the increase in DNR orders with age or the
      disparity across diagnosis. Further evaluation is needed into whether variation
      in DNR order rates with age, diagnosis, race, gender, insurance status, and rural
      location represents differences in patient preferences or care compromising
      patient autonomy.

PMID- 7575065
TI  - Outcomes of patients with do-not-resuscitate orders. Toward an understanding of
      what do-not-resuscitate orders mean and how they affect patients.
AB  - OBJECTIVES: To evaluate the outcomes of hospitalized patients with do-not
      resuscitate (DNR) orders and to identify variables that may elucidate the high
      mortality of patients with DNR orders. METHODS: Among a nationally representative
      sample of Medicare patients hospitalized with congestive heart failure, acute
      myocardial infarction, pneumonia, cerebrovascular accident, or hip fracture, we
      retrospectively studied in-hospital and 180-day mortality and hospital lengths of
      stay for patients without DNR orders, with early (day 1 or 2) DNR orders, and
      with late (day 3 or later) DNR orders, before and after adjustment for sickness
      at hospital admission and patient and hospital characteristics. RESULTS: In
      hospital mortality for patients with DNR orders exceeded that for patients
      without DNR orders before adjustment (59% vs 8%, P < .001), and after accounting
      for differences in sickness at admission and patient and hospital characteristics
      (40% vs 9%, P < .001). Sicker patients were assigned earlier DNR orders. Yet,
      patients with early DNR orders had a lower adjusted in-hospital mortality (31% vs
      49%, P < .001) and shorter hospital stay (10 vs 18 days, P < .001) than did
      patients with late DNR orders. CONCLUSIONS: Hospitalized older patients with DNR
      orders have a much higher mortality than predicted by admission demographic and
      clinical characteristics. The differential association of early and late DNR
      orders with mortality indicates that DNR orders represent a heterogeneous group
      of interventions that may be a marker of unmeasured sickness and a determinant of
      quality of care. A better understanding of what the DNR order represents and its
      effect on patient care is needed to ensure optimal use.

PMID- 7575066
TI  - Epoetin alfa for the treatment of the anemia of multiple myeloma. A prospective,
      randomized, placebo-controlled, double-blind trial.
AB  - BACKGROUND: To determine the efficacy of epoetin alfa for the treatment of the
      anemia of multiple myeloma, a prospective, randomized, placebo-controlled, double
      blind clinical trial enrolled 25 patients with the anemia of multiple myeloma and
      a hematocrit less than 0.30. METHODS: Epoetin alfa, 150 U/kg, or a matching
      volume of placebo was administered subcutaneously three times per week for 6
      weeks. If the criterion for a response was not met, the dose was doubled. After
      12 weeks, nonresponders in the placebo arm were switched to an open-label study
      of epoetin alfa at a dose of 150 U/kg for 6 weeks. After 6 weeks, the dose was
      doubled if no response was obtained. A partial response was defined as an
      increase of 6 percentage points or greater in the hematocrit without transfusion.
      A complete response required a final hematocrit of 0.38 or greater without
      transfusion. Complete responders had reduction of epoetin alfa to the lowest dose
      capable of maintaining the complete response. RESULTS: Twenty patients were
      evaluable for response to therapy. During the double-blind phase, six patients
      who were receiving epoetin alfa had a complete response, one had a partial
      response, and three were non-responders. No responses occurred in the placebo
      arm. In the open-label phase, of the 10 patients who were originally receiving
      placebo, three had a complete response, one had a partial response, and six were
      nonresponders. Chemotherapy, pretreatment serum erythropoietin levels, disease
      duration, and reticulocyte count did not predict the response to epoetin alfa.
      The median final dose for the responding group was 120 U/kg three times per week
      to maintain a hematocrit greater than 0.38. There was no effect on the course of
      the myeloma, and no hypertension was seen. CONCLUSION: Treatment with epoetin
      alfa is effective and safe in patients with the anemia of multiple myeloma.

PMID- 7575067
TI  - Adult hemolytic-uremic syndrome. A review of 37 cases.
AB  - BACKGROUND: Adult hemolytic-uremic syndrome is a serious, poorly understood
      disease with a high and variable mortality. We studied several demographic,
      clinical, and treatment variables, related them to outcome, and developed a new
      classification. METHODS: We analyzed data from 37 patients admitted from 1981 to
      1991 who fulfilled four criteria (age > 16 years, microangiopathic hemolytic
      anemia, creatinine level > 150 mumol/L [> 1.7 mg/dL], and no artificial heart
      valve). Three outcome variables were studied (survival vs death, recurrence vs no
      recurrence, and chronic renal failure vs no chronic renal failure). RESULTS:
      Eleven (30%) of the patients died, 10 (27%) needed dialysis, five (14%) developed
      chronic renal failure, and nine (24%) had recurrent episodes. Patients who
      presented with colitis did not die or have recurrences, but they developed
      chronic renal failure as often as other patients. Patients with hemolytic-uremic
      syndrome secondary to other diseases had the worst survival and the most
      recurrences. Those without any triggering factor (primary cases) were in between.
      In multivariate analysis, hemolytic-uremic syndrome secondary to colitis, a
      higher white blood cell count at admission, and a high maximum mean arterial
      pressure were associated with good survival prognosis. CONCLUSIONS: The
      persistence of the trigger of adult hemolytic-uremic syndrome sets the stage for
      outcome. If the trigger is transient (such as Escherichia coli colitis), the
      disease will not recur and is rarely lethal. If no trigger is apparent (primary
      hemolytic-uremic syndrome) or the trigger persists (systemic lupus erythematosus
      and cancer), the syndrome has a high mortality and often recurs. We suggest a new
      classification: (1) extrinsic hemolytic-uremic syndrome: (a) toxic, (b)
      infectious; (2) intrinsic hemolytic-uremic syndrome: (a) primary, (b) secondary.
      The use of this classification, combined with simple data obtained at
      presentation and a further division of the cause as transient or persistent and
      irreversible, may improve the selection of therapy.

PMID- 7575068
TI  - The quality of life of patients with life-threatening arrhythmias.
AB  - BACKGROUND: The treatment of life-threatening arrhythmias with amiodarone or an
      implantable cardioverter/defibrillator prolongs patient survival but with
      significant comorbidity. Previous studies have shown diminished health status and
      increased psychologic distress and inferred a diminished quality of life;
      however, a multidimensional analysis of quality of life, including patient
      perception, has not been performed. METHODS: One hundred four consecutive
      patients were surveyed regarding patient demographics, health status, psychologic
      distress, and patient-perceived quality of life. The patients were treated with
      amiodarone (n = 30) with an implantable cardioverter/defibrillator (n = 45) and
      the remainder were reference patients (n = 29). RESULTS: This study confirms that
      patients who survive life-threatening arrhythmias have diminished health status
      and increased psychologic distress; however, patient-perceived quality of life is
      preserved. These patients report a better perceived quality of life (as measured
      by the Quality of Life Index) than the reference group (22.3 +/- 4.0 vs 20.5 +/-
      4.4, P < .05) and their scores are similar to those of normal healthy volunteers
      (mean score, 21.9). The improved quality of life scores were not dependent on
      treatment modality (22.1 +/- 4.0 vs 22.4 +/- 4.1 for medical vs surgical groups,
      respectively). CONCLUSIONS: Patient-perceived quality of life is maintained in
      patients who survive life-threatening arrhythmias despite their diminished health
      status and increased psychologic distress. Measured quality of life is
      independent of treatment modality. Thus, caution must be exercised in assuming a
      diminished quality of life in patients who have survived a life-threatening
      cardiac event.

PMID- 7575069
TI  - The successful application of a heparin nomogram in a community hospital.
AB  - BACKGROUND: Heparin administration by physicians can vary greatly, and this
      variance can result in ineffective anticoagulation and reduced effectiveness of
      treatment. OBJECTIVE: To examine the use of a heparin nomogram in two community
      hospitals to validate its effect on anticoagulation parameters and to determine
      its influence on length of hospital stay. METHODS: Prenomogram and postnomogram
      intervention in two community hospitals in Sudbury, Ontario. All patients who
      presented and were admitted to the hospitals between 1991 and 1994 with a
      confirmed primary diagnosis of deep vein thrombosis and/or pulmonary embolism
      were eligible for the study. A heparin nomogram was instituted in April 1993 for
      treatment of deep vein thrombophlebitis and pulmonary embolism in hospitalized
      patients. The study patients were designated as prenomogram or postnomogram.
      Anticoagulation parameters (time to therapeutic activated partial thromboplastin
      time), number of diagnostic tests, percentage of times within the therapeutic
      range, and length of hospital stay were recorded for both groups. RESULTS: A
      total of 326 patients were identified from the database; 163 (50%) met the
      inclusion criteria. Patients in both groups appeared to be similar. Adequate
      anticoagulation was achieved faster (17.9 hours postnomogram vs 48.8 hours
      prenomogram; P < .001) and remained subtherapeutic less frequently in the
      postnomogram group (number of activated partial thromboplastin time tests below
      the therapeutic window; 56% prenomogram vs 28% postnomogram; P < .001). There
      were no differences between the groups with respect to length of stay (11.3 days
      prenomogram vs 10.9 days postnomogram; P = .60). More activated partial
      thromboplastin time tests were ordered in the postnomogram group (15.6
      postnomogram vs 12.7 prenomogram; P = .001); however, fewer prothrombin time
      tests were ordered in the postnomogram group. CONCLUSIONS: A heparin nomogram was
      successfully used in a community hospital without a structured hematology
      thrombosis service. Therapeutic anticoagulation was achieved faster and
      maintained more frequently, with less logistical problems, with this protocol.
      However, additional measures may be required to reduce the length of hospital
      stay.

PMID- 7575070
TI  - Strategy that includes serial noninvasive leg tests for diagnosis of
      thromboembolic disease in patients with suspected acute pulmonary embolism based
      on data from PIOPED. Prospective Investigation of Pulmonary Embolism Diagnosis.
AB  - OBJECTIVE: To estimate the percentage of patients with suspected acute pulmonary
      embolism in whom a noninvasive diagnosis or exclusion of thromboembolic disease
      might be safely made on the basis of ventilation-perfusion (VQ) lung scans,
      single noninvasive tests of the lower extremities, and, in patients with adequate
      cardiorespiratory reserve, serial noninvasive tests of the lower extremities.
      METHODS: Calculations were made among 662 patients who participated in the
      collaborative study Prospective Investigation of Pulmonary Embolism Diagnosis
      (PIOPED) and who had blood gas values measured while breathing room air and who
      underwent pulmonary angiography. The diagnostic strategy recommends treatment in
      all patients with a high-probability VQ scan and no treatment in patients with
      nearly normal VQ scans. In patients with nondiagnostic VQ scans (intermediate- or
      low-probability scans), a single noninvasive leg test is recommended. It was
      assumed that 50% of patients with pulmonary embolism would show deep venous
      thrombosis with a single noninvasive leg test. If results are abnormal, treatment
      is indicated. If normal, serial noninvasive leg tests are recommended. Treatment
      can be withheld if results of serial tests are normal. In patients with poor
      cardiorespiratory reserve, pulmonary angiography is indicated. RESULTS: A single
      noninvasive leg test in patients with nondiagnostic VQ scans would show deep
      venous thrombosis and, therefore, eliminate the need for pulmonary angiography in
      53 (11%) of 468 patients (95% confidence interval [CI], 9% to 15%) who otherwise
      would require angiography. Serial noninvasive leg tests in patients with adequate
      cardiorespiratory reserve who had a normal result of a single leg test would
      either show deep venous thrombosis or exclude it in 222 (47%) of 468 patients
      (95% CI, 43% to 52%). The need for pulmonary angiography, therefore, would be
      reduced from 468 (71%) of 662 (95% CI, 67% to 74%) if no noninvasive leg tests
      were performed to 415 (63%) of 662 (95% CI, 59% to 66%) if only a single
      noninvasive leg test were performed, and further reduced to 193 (29%) of 662 (95%
      CI, 26% to 33%) if serial noninvasive leg tests were used where appropriate.
      CONCLUSION: A noninvasive strategy that includes VQ scans, single noninvasive leg
      tests, and serial noninvasive leg tests would permit a diagnosis of
      thromboembolic disease or a safe exclusion of thromboembolic disease in 71% of
      patients with suspected acute pulmonary embolism.

PMID- 7575071
TI  - Outcome and prognosis of patients with chronic fatigue vs chronic fatigue
      syndrome.
AB  - BACKGROUND: There are few data on the natural history and prognosis of persons
      with chronic fatigue (CF) or CF syndrome (CFS). Therefore, we compared functional
      outcomes in patients with each condition and tested the validity of various
      prognostic indicators. METHODS: Four hundred forty-five (89%) of 498 consecutive
      referral patients were surveyed an average of 1.5 years after an initial
      evaluation. Data from the initial evaluation were used to predict outcomes.
      RESULTS: Sixty-four percent of all patients reported improvement, but only 2%
      reported complete resolution of symptoms. Patients initially diagnosed as having
      CFS reported greater symptom severity and lower level of functioning at follow-up
      than did patients with CF. Major depression predicted unemployment in the CF
      group. Older age, longer duration of illness, and a lifetime history of dysthymia
      predicted less improvement in the CF group. Current dysthymia predicted less
      improvement for the CFS group. CONCLUSIONS: The case definition of CFS according
      to the Centers for Disease Control and Prevention identifies chronically fatigued
      patients with poorer prognosis. In a tertiary care setting, recovery from CF or
      CFS is rare, but improvement is common. Prognostic indicators vary for the two
      groups, but the coexistence of dysthymia suggests poorer outcomes generally.

PMID- 7575072
TI  - Instability of delayed-type hypersensitivity skin test anergy in human
      immunodeficiency virus infection.
AB  - OBJECTIVE: To evaluate stability of delayed-type hypersensitivity (DTH) skin test
      over time in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative
      injecting drug users. METHOD: A community-based cohort of injecting drug users
      who had serial skin testing with purified protein derivative tuberculin, mumps,
      and Candida albicans antigen. Delayed-type hypersensitivity anergy was defined as
      a skin test result of less than 3 mm for all three antigens; DTH positivity was a
      skin test result of 3 mm or greater for at least one antigen (Centers for Disease
      Control and Prevention, Atlanta, Ga, 1993). RESULTS: At baseline, 36% of HIV
      seropositive subjects (n = 401) were anergic as compared with 14% of HIV
      seronegative subjects (n = 552; P < .001). During follow-up, fewer HIV
      seropositive subjects remained DTH positive (42%) and more remained anergic (19%)
      than of HIV-seronegative subjects (67% and 7%, respectively). Twenty-four percent
      of HIV-seropositive subjects who were initially DTH positive became anergic as
      compared with 15.3% of the HIV-seronegative subjects. However, the proportion
      changing from anergy to DTH positivity was greater among HIV-seropositive
      subjects (15%) than HIV-seronegative subjects (12%). In comparison to those who
      remained DTH positive, HIV-seropositive subjects with CD4 cell counts of less
      than 0.50 x 10(9)/L (odds ratio = 6.4) and less than 0.35 x 10(9)/L (odds ratio =
      11.2) were more likely to remain anergic than those who had CD4 cell counts above
      0.50 x 10(9)/L or were HIV seronegative. CONCLUSIONS: Although the prevalence and
      incidence of DTH anergy were higher in HIV-seropositive subjects, high rates of
      change in DTH status occurred in both directions. This suggests that instability
      of DTH skin testing is substantial and only partially dependent on HIV status.
      Although a single test may be an unreliable indicator of HIV-induced
      immunosuppression, two consecutive anergic readings were strongly associated with
      a CD4 cell count below 0.50 x 10(9)/L and particularly below 0.35 x 10(9)/L. For
      determining false negativity of tuberculin tests, persistent DTH anergy is more
      reliable than a single test among HIV-seropositive injecting drug users. Anergy
      testing appears to be unnecessary with CD4 cell counts greater than 0.5 x
      10(9)/L.

PMID- 7575073
TI  - Beneficial effect of digoxin-specific Fab antibody fragments in oleander
      intoxication.
AB  - A 24-year-old man presented to the emergency department with nausea, vomiting,
      abdominal pain, and an acute confusional state of 6 hours' duration. Ten hours
      before admission, he had ingested a mixture of orange juice and six ground
      leaves, later identified as Nerium oleander (common pink oleander) leaves. His
      blood pressure was 100/80 mm Hg, and his pulse rate was irregular at 40/min. He
      was disoriented and his speech was dysarthric. Twelve-lead electrocardiography
      revealed a complete atrioventricular block, with a nodal escape rhythm of 40/min
      and diffuse ST depression. The presumptive diagnosis of acute oleander
      intoxication was confirmed by the detection of digoxin (1.0 nmol/L [0.8 ng/mL])
      on radioimmunoassay. Despite intensive therapy, the patient's hemodynamic
      condition deteriorated. His blood pressure decreased to 70/40 mm Hg; he became
      oliguric and nonresponsive to external stimuli; and his potassium concentration
      rose to 6.8 mmol/L. Eighteen hours after admission, an empiric 480-mg dose of
      digoxin-specific Fab antibody fragments was administered intravenously over 30
      minutes. Within minutes of the initiation of immunotherapy, the patient woke up;
      his blood pressure rose to 90/50 mm Hg; and he regained a sinus rhythm of 68/min
      with a prolonged PR interval. His potassium concentration decreased to 5.1 mmol/L
      within 15 minutes and normalized within 1 hour of therapy initiation. One day
      later, the 1 degree atrioventricular block disappeared, but the ST depression
      persisted for an additional 6 days. The value of digoxin-specific Fab antibody
      fragments in the treatment of plant glycoside and, in particular, oleander
      intoxication is discussed.

PMID- 7575074
TI  - Intravenous vitamin K1 injections: dangerous prophylaxis.

PMID- 7575075
TI  - Mycobacterium genavense infection and survival.

PMID- 7575076
TI  - Skin depigmentation related to transdermal clonidine therapy.

PMID- 7575077
TI  - [Human embryology: molecular basis, morphogenesis mechanisms, and applications].

PMID- 7575078
TI  - [Morphologic adaptation of the vertebrate eye to the environment].

PMID- 7575079
TI  - Renal ischemia and pharmacological prevention: experimental structural and
      ultrastructural observations.
AB  - Defibrotide is a polydeoxiribonucleotid derived from the bovine's lung. It
      stimulates the release of prostacyclines (PGI2) from the vascular endothelium,
      thus determining profibrinolytic, antithrombotic, and thrombolytic actions. These
      activities have been experimentally demonstrated by several authors in different
      animal species through models of ischemia in different organs. The aim of the
      present study was to carry out an experimental model of acute renal insufficiency
      with a bilateral and temporal hot ischemia in order to confirm by light
      microscopy the structural alterations, and by transmission and scanning electron
      microscopy the ultrastructural alterations, and therefore establish the effects
      of Defibrotide in preventing reperfusion injuries. Kidney samples were observed
      as a blind-trial by three different operators. A certain preventive effect
      against ischemia was evidenced, probably due to the cytoprotective action of
      Defibrotide in close relation also with an increase in PGI2 production.

PMID- 7575080
TI  - The original calibre of the lower limbs arteries as a possible risk factor for
      complications of atherosclerosis: a statistical investigation in 90 subjects by
      echocolor-doppler.
AB  - Ninety subjects with emodynamically significant atherosclerotic disease of the
      lower limbs were examined. They had no history of diabetes mellitus or
      hypertension. Each subject underwent a color Doppler ultrasonographic study of
      the common iliac, superficial femoral, and popliteal arteries. In each arterial
      segment, diameter and blood flow velocity were measured. In evaluating the
      hemodynamic significance of the stenoses, we used the Windsor method. In a
      comparison of the calibers of the arteries significant relationship emerged in
      each given subject in two sexes. Males: a statistically significant difference
      was found only in the iliac artery, in which the calibre and Windsor indices were
      greater in the right as compared to the left; right: 1) There was a statistically
      significant relationship between mean caliber and Windsor indices, (p < 0.01); 2)
      there was a statistically significant correlation between mean calibre and age (p
      < 0.05); Left: 1) There was a statistically significant correlation between mean
      calibre and Windsor indices calculated at the levels of both the posterior
      tibialis (p < 0.05) and dorsalis pedis arteries (p < 0.01); 2) there was a
      statistically significant correlation between mean calibre and age (p < 0.05).
      Females: Student's t test for paired samples of the three arteries did not reveal
      a statistically significant predominance of one side over the other. With respect
      to the coefficients of correlation between mean calibre and Windsor indices, the
      results were as follows. Right: 1) There was a statistically significant
      correlation between mean calibre and Windsor indices calculated at the levels of
      both the posterior tibialis and dorsalis pedis arteries (p < 0.01); 2) there was
      a statistically significant correlation between age and mean calibre (p < 0.05);
      Left: 1) There was a statistically significant correlation between mean calibre
      and Windsor indices calculated at the levels of both the posterior tibialis (p <
      0.05) and dorsalis pedis arteries (p < 0.01); 2) there was a statistically
      significant correlation between mean calibre and age (p < 0.05).

PMID- 7575081
TI  - Magnetic resonance in the study of cranial nerves.
AB  - The course of cranial nerves was studied by means of magnetic resonance (MR),
      which allowed a multiplane visualization of the investigated structures. The
      obtained results showed that MR was an excellent method for visualization of the
      optic, trigeminal, facial and acoustica nerves. The oculomotor and the abducent
      nerves were detectable only in some regions where the contrast with the
      surrounding structures was greater. The glossopharingeus, vegus and accessory
      nerves were identifiable only in the first tract of emergency from the encephalic
      trunk and they could no be distinguished separately. The trochlear nerve was
      seldom visible whereas the olfactory nerve failed to be revealed. Further
      technological progress will allow for additional advances as regards the
      acquisition of knowledge concerning these important nerves.

PMID- 7575082
TI  - Neuronal populations in the spinal cord during ageing.
AB  - The sensory and motor fibres of the spinal cord and the relative centres of
      integration were studied during ageing. Sections of spinal cord and ganglia from
      C8 to T12 of rats aged 6 and 24 months were treated using several techniques:
      Nissl, NADPH-diaphorase, and antibodies to enkephalins, substance P and
      neuropeptide Y. Nissl staining of the C8 segment showed that in the aged rat the
      dorsal horn was more oblique and narrow, the central canal was enlarged, the
      cellular density was reduced, and the neurons of the intermediolateral and
      ventral horns and of lamina IV were smaller. The total number of NADPH-diaphorase
      positive cells of C8 segment was similar in the adult and in the aged rats.
      However, in the aged rat the number of cells was reduced in laminae I, II, III,
      VII and IX, remained the same in laminae V, VI and X, and was increased in
      laminae IV and VIII, and in the intermediolateral and intermediomedial horns. In
      the adult rat, we saw a greater number of cells with a lower expression of the
      enzyme. The area of the cells in laminae V and IX was reduced in the aged rat. In
      the C8 segment substance P was present in laminae I and II: in the aged rat the
      immunoreactivity was reduced and more diffuse. Enkephalins are present in laminae
      I, II and III, with a reduced immunoreactivity in the aged rat. NPY is present in
      the central canal in the adult rat and, is also present in laminae I and II in
      the aged rat.

PMID- 7575083
TI  - [Detection of micrometastasis in the patients with malignant tumors].

PMID- 7575084
TI  - Extracorporeal shock wave lithotripsy (ESWL) for biliary stones: a nationwide
      survey in Japan.
AB  - To assess the current status of extracorporeal shock wave lithotripsy (ESWL) for
      the treatment of gall-stones in Japan, we conducted a nationwide survey by
      sending a questionnaire to 251 institutions using this therapy. Replies were
      obtained from 50 institutions. The use of ESWL was investigated over the period
      from its introduction up to October 1992. ESWL was performed on 2,760 of 10,058
      patients with gallstones (27.4%). The stones were completely pulverized in 1,021
      of these 2,760 patients (37.0%). Complete disappearance was limited to single
      gallstones less than 20 mm in maximum diameter. A comparison in the number of
      ESWL sessions revealed no significant difference between the patients with and
      without a good response. Choledocholithiasis was resolved completely in 44.0% of
      157 patients who underwent ESWL for this condition and intrahepatic stones were
      cured in 18.7% of 32 patients. Therefore, ESWL may be a useful form of
      conservative therapy for biliary calculi.

PMID- 7575085
TI  - Benign schwannoma of the liver: a case report.
AB  - Neurogenic tumors of the liver are very rare, irrespective of associated
      neurofibromatosis. We report here a well-documented case of benign schwannoma in
      a 56-year-old woman without neurofibromatosis, including imaging and pathological
      examinations.

PMID- 7575086
TI  - Complete obstruction of the inferior vena cava due to chronic relapsing
      pancreatitis: a case report.
AB  - A woman aged 62 with long history of chronic relapsing pancreatitis presented
      with swelling and ulcer in the lower limbs and occasional gastrointestinal
      bleeding. The radiological imaging showed complete obstruction of Inferior Vena
      Cava (IVC) at the level of the pancreas and well developed collateral vessels.
      Portal vein and splenic vein were also obstructed and superior mesenteric venous
      blood drained into the liver via coronary vein. She was originally found to have
      pancreas head tumor, which was not resectable. A palliative operation was
      performed, but histological examination of pancreatic specimen suggested only
      chronic inflammation and no evidence of malignancy. She was diagnosed as tumor
      forming type chronic pancreatitis. Although SPV or SMV-PV obstruction has been
      recognized as a complication of chronic pancreatitis, IVC obstruction can occur
      by the same mechanism. This is the only case but one ever reported. Not only
      splenoportography but IVC-graphy will contribute to more precise understanding of
      patient's condition with chronic pancreatitis.

PMID- 7575087
TI  - [Joy riding: multiple criminal car rides in an intoxicated state in relation to
      dyssocial personality with addictive tendencies].
AB  - Going out from the case report of a young unskilled worker, the author introduces
      a little known behavioral disorder, named "joy riding". This highly problematic
      pattern of misbehavior includes the stealing of usually high-powered motorcars in
      order to take fast and joyful trips without any goal and leaving them anywhere in
      a more or less damaged state. As our case report shows, this special behavior
      sometimes develops features of an addiction and thereby similarities to addictive
      behaviors like pathological gambling, kleptomania, pyromania and others. Rightly,
      we find in literature several statements denying clearly the nosological
      independence of all these non-substance-bound addictive behaviors, pointing out
      the underlying deficiency of impulse control building the common ground to all
      these addiction-like disorders.

PMID- 7575088
TI  - [Suicidal hanging or homicide? On the criminal significance of "professional
      knots"].

PMID- 7575089
TI  - [Person identification with video super-projection].
AB  - The author reports on the identification of a male corpse which was found in a
      marsh where it had been lying for approximately three months. Autopsy revealed a
      laceration of the scalp with an underlying skull fracture. Since the corpse could
      not be identified by means of dental status, bloodgrouping or finger prints, the
      method of videosuperimposition was used. A comparison of the skull with a
      photograph of the suspected victim confirmed identity.

PMID- 7575090
TI  - [Fatalities associated with methadone administration in the Geneva canton (1987
      1993)].
AB  - In Geneva 41 deaths associated with methadone have been observed between 1987 and
      1993. In 11 cases death was caused by heroin overdose in combination with
      methadone. In 6 other cases (natural death, hanging, murder, road accident,
      drowning and burning) methadone, although in feeble doses, could have played a
      role in the circumstances leading to death. In 24 other cases, where methadone
      was the sole cause of death, 10 of these were in individuals participating in
      Methadone Maintenance Schemes, but none in the first two weeks of the scheme, 8
      occurred in the year following release from prison (3 less than two weeks after
      release), 11 were associated with a parallel intake of benzodiazepines and 8 with
      an intake of alcohol.

PMID- 7575091
TI  - [Possible errors in measuring gunshot distance with ricochet full jacket
      projectiles].
AB  - Experiments with ricocheted 9 mm Luger full jacket projectiles showed results
      which feign shots from short distance. The morphology of the wound and the
      destruction in textile is very varying. The marks of scattered lead were examined
      by micro radiography.

PMID- 7575092
TI  - [The value of various lung changes in death by strangulation].
AB  - Subsequently to previous investigations the value of the parameters lung weight
      and alterations of pulmonary vessel contents is demonstrated in a group of 106
      fatal strangulations including all important subtypes of compressing force
      against the neck. The mean combined lung weights were generally elevated in a
      distinct way in all fatalities due to strangulating force (average: 1201 g)
      exhibiting a great interindividual variability and a slight dependence upon age
      with lower values in older persons. Significant differences between the various
      types of strangulation could not be observed. A detailed analysis of the material
      revealed, that intravascular pulmonary cell accumulations--apart from individual
      cases with massive concomitant blunt force injuries--in the first place are a
      correlate for protracted agony courses (shock equivalents). Both pulmonary
      parameters investigated cannot prove the diagnosis "death due to strangulation".

PMID- 7575093
TI  - [Catecholamines, myofibrillary degeneration of the heart muscle and cardiac
      troponin T in various types of agony].
AB  - The stress of agony (the death struggle) induces a rise in serum catecholamines.
      High doses of catecholamines cause myofibrillar degeneration (MFD), a form of
      cardiac injury. Severely damaged cardiac myocytes release troponin T (TnT), a
      myofibrillar cardiac protein, into the circulation. We studied serum
      catecholamine levels, MFD and TnT in 119 medico-legal autopsy cases.
      Catecholamine levels increased with the duration of agony: In the instantaneous
      death cases, the levels were similar to levels in humans at rest, whereas the
      levels in prolonged agony were comparable to concentrations found in humans in
      acute maximal stress. Still, it was not possible to infer the duration of agony
      from the catecholamine level in an individual case. The exceptionally high
      dopamine levels found in the group 'resuscitation and/or intensive care before
      death 'were most likely caused by antemortal treatment with dopamine. Slight MFD
      was diagnosed in nearly all hearts; its severity was neither related to
      catecholamine levels nor to duration of agony. TnT, not found in blood of healthy
      people, was present in nearly all postmortem samples, indicating autolytic
      effects. Heart blood contained more TnT than femoral blood. We could not detect a
      relationship between the serum cardiac troponin T level and MFD; but cardiac
      deaths had significantly higher levels of TnT in heart blood than deaths from
      other causes. The postulated interrelation between catecholamines, MFD and TnT
      was not evident from the results.

PMID- 7575094
TI  - [Homicide by strangulation with a lasso sling].
AB  - A 50-year-old physically handicapped man was found dead on his wheelchair in a
      short passage on the ground floor of a high-rise housing development. The lattice
      doors at the both ends of the passage were closed and the wheelchair with the
      body was found at the door to an adjoining indoor parking place for bicycles. A
      noose of a vinyl plastic cord was found wound around the neck; the other end of
      the cord was tied through the lattice door to a handrail on the wall of the
      parking place. The wheelchair was stopped sideways; its chair back was in contact
      with a doorpost. The body which was slipped from the seat of the wheelchair was
      incompletely suspended by the noose. The cause of death primarily was diagnosed
      as hanging. The police suspected murder and arrested a 21-year-old male
      assailant. According to his confession, the assailant pushed the wheelchair
      through the lattice door in the passage, stopped it at the door and braked it.
      Immediately thereafter he returned to the parking place and locked the lattice
      door behind him. After having made a kind of lasso using a cord taken off from a
      bicycle which has been sitting there, he reached out his hands through the
      lattice door and lassoed the man on the wheelchair from behind. Finally, he tied
      another end of the lasso to the handrail. It was considered that the body of the
      victim was slipped down in the stage of convulsion and incompletely suspended by
      the noose.

PMID- 7575095
TI  - Isolation and characterization of sulfur globule proteins from Chromatium vinosum
      and Thiocapsa roseopersicina.
AB  - Purple sulfur bacteria store sulfur as intracellular globules enclosed by a
      protein envelope. The proteins associated with sulfur globules of Chromatium
      vinosum and Thiocapsa roseopersicina were isolated by extraction into 50% aqueous
      acetonitrile containing 1% trifluoroacetic acid and 10 mM dithiothreitol. The
      extracted proteins were separated by reversed-phase HPLC, revealing three major
      proteins from C. vinosum and two from T. roseopersicina. All of these proteins
      have similar, rather unusual amino acid compositions, being rich in glycine and
      aromatic amino acids, particularly tyrosine. The molecular masses of the C.
      vinosum proteins were determined to be 10,498, 10,651, and 8,479 Da, while those
      from T. roseopersicina were found to be 10,661 and 8,759 Da by laser desorption
      time-of-flight mass spectrometry. The larger T. roseopersicina protein is N
      terminally blocked, probably by acetylation, but small amounts of the unblocked
      form (mass = 10,619) were also isolated by HPLC. Protein sequencing showed that
      the two larger C. vinosum proteins are homologous to each other and to the large
      T. roseopersicina protein. The 8,479 Da C. vinosum and 8,759 Da T. roseopersicina
      proteins are also homologous, indicating that sulfur globule proteins are
      conserved between different species of purple sulfur bacteria.

PMID- 7575096
TI  - Purification, primary structure, and evolution of cytochrome c-550 from the
      magnetic bacterium, Magnetospirillum magnetotacticum.
AB  - Cytochrome c-550 was purified from Magnetospirillum magnetotacticum to an
      electrophoretically homogeneous state, and some of its properties were
      determined. The cytochrome showed absorption peaks at 528 and 409 nm in the
      oxidized form, and at 550, 521, and 414 nm in the reduced form. Its midpoint
      redox potential at pH 7.0 was determined to be +289 mV. The primary structure of
      cytochrome c-550 was determined. Cytochrome c is composed of 97 amino acid
      residues, and its molecular weight was calculated to be 10,873, including heme c.
      Its primary structure is very similar to those of Rhodospirillum fulvum and
      Rhodospirillum molischianum cytochromes c2, suggesting that M. magnetotacticum is
      phylogenetically related to photosynthetic bacteria.

PMID- 7575097
TI  - Purification and properties of benzyl alcohol dehydrogenase from a denitrifying
      Thauera sp.
AB  - Toluene and related aromatic compounds are anaerobically degraded by the
      denitrifying bacterium Thauera sp. strain K172 via oxidation to benzoyl-CoA. The
      postulated initial step is methylhydroxylation of toluene to benzyl alcohol,
      which is either a free or enzyme-bound intermediate. Cells grown with toluene or
      benzyl alcohol contained benzyl alcohol dehydrogenase, which is possibly the
      second enzyme in the proposed pathway. The enzyme was purified from benzyl
      alcohol-grown cells and characterized. It has many properties in common with
      benzyl alcohol dehydrogenase from Acinetobacter and Pseudomonas species. The
      enzyme was active as a homotetramer of 160 kDa, with subunits of 40 kDa. It was
      NAD(+)-specific, had an alkaline pH optimum, and was inhibited by thiol-blocking
      agents. No evidence for a bound cofactor was obtained. Various benzyl alcohol
      analogues served as substrates, whereas non-aromatic alcohols were not oxidized.
      The N-terminal amino acid sequence indicates that the enzyme belongs to the class
      of long-chain Zn(2+)-dependent alcohol dehydrogenases, although it appears not to
      contain a metal ion that can be removed by complexing agents.

PMID- 7575098
TI  - Properties of the menaquinol oxidase (Qox) and of qox deletion mutants of
      Bacillus subtilis.
AB  - Menaquinol oxidase isolated from the membrane of Bacillus subtilis W23 was found
      to consist of four polypeptides (QoxA, B, C, and D) that were predicted by the
      sequence of the qox operon of B. subtilis 168 (Santana et al. 1992). The
      preparation contained 7 mol cytochrome aa3 per g protein, which corresponds to 2
      mol heme A per mol enzyme of 144 kDa molecular mass. Respiration with
      dimethylnaphthoquinol catalyzed by the enzyme was ten times faster than that with
      menadiol. Activities with more electropositive quinols were negligible. The
      activity of the enzyme was inhibited by equimolar amounts of HQNO, while
      antimycin, myxothiazol, and stigmatellin were more than tenfold less effective.
      When cells of both strains of B. subtilis (W23 and 168) were grown with glucose,
      quinol respiration was an order of magnitude more active than respiration with
      N,N,N',N'-tetramethyl-1,4-phenylenediamine plus ascorbate. Surprisingly, the same
      result was obtained with mutant strains lacking qoxB. As cytochromes a and d were
      virtually absent, a second quinol oxidase, possibly of the cytochrome o-type, was
      apparently formed by the mutants.

PMID- 7575099
TI  - Characterization of the Rhodococcus sp. NI86/21 gene encoding alcohol: N,N'
      dimethyl-4-nitrosoaniline oxidoreductase inducible by atrazine and thiocarbamate
      herbicides.
AB  - A protein with a mol.mass of 51,000 (ThcE) that was induced in Rhodococcus sp.
      NI86/21 during assimilation of thiocarbamate herbicides, atrazine, ethanol,
      propanol, glycerol, propionaldehyde or ethanolamine was identified by two
      dimensional electrophoresis. The thcE gene was cloned and sequenced. The deduced
      amino acid sequence revealed ThcE as a member of group III alcohol
      dehydrogenases. ThcE displayed strong homology with sequenced subunit fragments
      of the homodecameric N,N'-dimethyl-4-nitrosoaniline-dependent alcohol
      oxidoreductases (MNO) of Amycolatopsis methanolica and Mycobacterium gastri. N
      Terminal sequence analysis of purified MNO from Rhodococcus sp. NI86/21 confirmed
      the identity with ThcE. When overproduced in Escherichia coli, ThcE was insoluble
      and no MNO activity was detected.

PMID- 7575100
TI  - Abnormally high neuronal density in the schizophrenic cortex. A morphometric
      analysis of prefrontal area 9 and occipital area 17.
AB  - BACKGROUND: In the past two decades, gross morphologic changes have been
      uncovered in the schizophrenic brain, eg, increased ventricular width and
      decreased cortical volume; however, relatively little is known about the area
      specific and laminar density of cells in the schizophrenic cortex, particularly
      in prefrontal areas. METHODS: A direct, three-dimensional counting method was
      used to determine cell density in 16 brains from patients with schizophrenia, 19
      from normal subjects, six from patients with schizoaffective disorder, and nine
      from patients with advanced-stage Huntington's disease. RESULTS: Increased
      neuronal density was found in prefrontal area 9 (17%) and occipital area 17 (10%)
      in the schizophrenic brains. In area 9, neuronal density was increased in layers
      III to VI; cell packing of pyramidal and nonpyramidal neurons was elevated.
      Cortical thickness in the schizophrenic brains was slightly but not significantly
      reduced in both areas, with a disproportionate reduction in layer V in area 9. In
      contrast, brains with Huntington's disease exhibited markedly higher glial
      density (50%) and drastically reduced cortical thickness (28%). CONCLUSION:
      Abnormally high density in the cerebral cortices of schizophrenics suggests that
      neuronal atrophy is the anatomic substrate for deficient information processing
      in schizophrenia.

PMID- 7575101
TI  - Spatial working memory deficits in the relatives of schizophrenic patients.
AB  - BACKGROUND: Studies in nonhuman primates provide evidence that intact spatial
      working memory depends on the integrity of specific areas in the prefrontal
      cortex. Patients with schizophrenia have been shown to be impaired on spatial
      working memory tasks. Relatives of schizophrenic patients show a range of
      cognitive deficits in the absence of clinical symptoms (eg, thought disorder, eye
      tracking dysfunctions). We predicted that a significant proportion of relatives
      of schizophrenic patients would show deficits in working memory as measured by a
      delayed response task. METHODS: In experiment 1, we tested 18 schizophrenic
      patients, 15 first-degree relatives of schizophrenic patients, and 18 normal
      control subjects on an oculomotor delayed response task. In experiment 2, we
      assessed the performance of another group of 12 first-degree relatives of
      schizophrenic patients and 16 different normal control subjects on a visual
      manual delayed response task. RESULTS: Relatives of schizophrenic patients showed
      significant deficits in working memory on both the oculomotor and visual-manual
      delayed response tasks. CONCLUSIONS: Some relatives of schizophrenic patients are
      impaired on tasks that tap spatial working memory and that implicate the
      prefrontal system. The delayed response paradigm may be useful in elucidating the
      multidimensionality of the schizophrenic phenotype.

PMID- 7575102
TI  - Abnormal excitatory neurotransmitter metabolism in schizophrenic brains.
AB  - BACKGROUND: Schizophrenia has been hypothesized to be caused by a hypofunction of
      glutamatergic neurons. Findings of reduced concentrations of glutamate in the
      cerebrospinal fluid of patients with schizophrenia and the ability of glutamate
      receptor antagonists to cause psychotic symptoms lend support to this hypothesis.
      N-acetylaspartylglutamate (NAAG), a neuropeptide that is highly concentrated in
      glutamatergic neurons, antagonizes the effects of glutamate at N-methyl-D
      aspartate receptors. Moreover, NAAG is cleaved to glutamate and N-acetylaspartate
      by a specific peptidase, N-acetyl-alpha-linked acidic dipeptidase (NAALADase). To
      test the glutamatergic hypothesis of schizophrenia, we studied the NAAG-related
      glutamatergic variables in postmortem brains from patients with schizophrenia,
      neuroleptic-treated controls, and normal individuals, with particular emphasis on
      the prefrontal cortex and hippocampus. METHOD: Different regions of frozen brain
      tissue from three different groups (patients with schizophrenia, neuroleptic
      treated controls, and normal controls) were assayed to determine levels of NAAG,
      N-acetylaspartate, NAALADase, and several amino acids, including aspartate and
      glutamate. RESULTS: Our study demonstrates alterations in brain levels of
      aspartate, glutamate, and NAAG and in NAALADase activity. Levels of NAAG were
      increased and NAALADase activity and glutamate levels were decreased in the
      schizophrenic brains. Notably, the changes in NAAG level and NAALADase activity
      in schizophrenic brains were more selective than those for aspartate and
      glutamate. In neuroleptic-treated control brains, levels of aspartate, glutamate,
      and glycine were found to be increased. CONCLUSIONS: The changes in levels of
      aspartate, glutamate, NAAG, and NAALADase are prominent in the prefrontal and
      hippocampal regions, where previous neuropathological studies of schizophrenic
      brains demonstrate consistent changes. These findings support the hypothesis that
      schizophrenia results from a hypofunction of certain glutamatergic neuronal
      systems. They also suggest that the therapeutic efficacy of neuroleptics may be
      related to increased glutamatergic activity.

PMID- 7575103
TI  - Plasma haloperidol levels and clinical effects in schizophrenia and
      schizoaffective disorder.
AB  - BACKGROUND: Plasma haloperidol levels between 5 and 11 ng/mL may be clinically
      optimal for acutely exacerbated schizophrenia, but the evidence for this
      therapeutic window has been inconsistent. METHODS: Haloperidol was administered
      in a double-blind manner during two consecutive 3-week experimental periods to 65
      patients with acutely exacerbated schizophrenia or schizoaffective disorder. Two
      plasma levels were targeted: "low" (2 ng/mL) and "moderate" (10 ng/mL). The
      subjects were randomly assigned to four treatment sequences (low-low, low
      moderate, moderate-moderate, or moderate-low). RESULTS: In the first 3 weeks, the
      antipsychotic efficacy of haloperidol increased with plasma levels up to
      approximately 12 ng/mL. In the second 3 weeks, decrease of plasma levels reduced
      negative symptoms. CONCLUSION: For most patients, plasma levels not exceeding 12
      ng/mL yield the best results in the first 3 weeks of treatment. Subsequent
      lowering of the plasma levels may improve negative symptoms.

PMID- 7575104
TI  - Suicidal behaviors and the tryptophan hydroxylase gene.
AB  - BACKGROUND: To determine whether the tryptophan hydroxylase gene (ie, the gene
      that codes for the rate-limiting enzyme in the metabolic pathway of serotonin)
      may be a susceptibility factor for suicidal behavior. METHODS: Genotypic and
      allelic frequencies at a polymorphic Ava II restriction site were revealed with
      the use of the complementary DNA tryptophan hydroxylase probe C2-38 in 62 suicide
      attempters. The psychiatric characteristics of these suicide attempters were
      determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime
      version with modification for the study of anxiety disorders, and these
      characteristics were compared with those in 52 healthy controls. RESULTS: No
      association between tryptophan hydroxylase and suicidal behavior was detected.
      CONCLUSION: The tryptophan hydroxylase gene was not a susceptibility factor for
      suicidal behaviors in the group of suicide attempters in this study.

PMID- 7575105
TI  - Health care costs of primary care patients with recognized depression.
AB  - BACKGROUND: While an extensive literature documents the influence of depression
      on general medical services utilization, estimates of the economic burden of
      depression have focused on the direct costs of depression treatment. Higher use
      of general medical services may contribute significantly to the true cost of
      depressive illness. METHODS: Computerized record systems of a large staff-model
      health maintenance organization (HMO) were used to identify consecutive primary
      care patients with visit diagnoses of depression (n = 6257) and a comparison
      sample of primary care patients with no depression diagnosis (n = 6257). The HMO
      accounting records were used to compare components of health care costs. RESULTS:
      Patients diagnosed as depressed had higher annual health care costs ($4246 vs
      $2371, P < .001) and higher costs for every category of care (eg, primary care,
      medical specialty, medical inpatient, pharmacy, laboratory). Similar cost
      differences were observed for each of the subgroups examined (patients treated
      with antidepressants, those not treated with antidepressants, and those diagnosed
      at routine physical examination visits). Pharmacy records indicated greater
      chronic medical illness in the diagnosed depression group, but large cost
      differences remained after adjustment ($3971 vs $2644). Twofold cost differences
      persisted for at least 12 months after initiation of treatment. CONCLUSIONS:
      Diagnosis of depression is associated with a generalized increase in use of
      health services that is only partially explained by comorbid medical conditions.
      In the primary care sector, this greater medical utilization exceeds direct
      treatment costs for depression. The persistence of utilization differences
      suggests that recognition and initiation of treatment alone are not adequate to
      reduce utilization differences.

PMID- 7575107
TI  - More reliable outcome measures can reduce sample size requirements.
AB  - In the design of a clinical trial, considerations of statistical power primarily
      involve the evaluation of prospective sample sizes. Another strategy for
      increasing statistical power that is rarely used focuses on the selection of the
      outcome measure. When an outcome measure is selected, its reliability and
      validity must be carefully evaluated. Here the relationship between reliability
      and statistical power is explored empirically. We show that as the number of
      related items in an outcome scale increases, the internal consistency reliability
      of the scale also increases. As a consequence, the within-group variability
      decreases and, in turn, the between-group effect size increases and sample size
      requirements decrease. As a result, sample size requirements can be reduced and
      research costs decreased. We recommend careful consideration of the psychometric
      properties of outcome measures prior to sample size determination in any
      statistical power analyses.

PMID- 7575106
TI  - The New York High-Risk Project. Psychoses and cluster A personality disorders in
      offspring of schizophrenic parents at 23 years of follow-up.
AB  - BACKGROUND: We herein present lifetime prevalence rates of psychoses and DSM-III
      R cluster A personality disorders in sample A of the New York High-Risk Project,
      a prospective study following offspring of parents with schizophrenia (HRSz
      subjects) and affective illness (HRAff subjects) and of psychiatrically normal
      parents (NC subjects) from midchildhood to adulthood. METHODS: We interviewed the
      offspring in adulthood with the Schedule for Affective Disorders and
      Schizophrenia, Lifetime Version, for Axis I disorders and the Personality
      Disorder Examination for Axis II disorders. RESULTS: Lifetime prevalence rates
      (+/- SE) of schizophrenia and unspecified psychosis were 11.1% +/- 4.3% and 5.6%
      +/- 3.1%, respectively, in the HRSz group and 0% in the HRAff and NC groups.
      Rates of schizoaffective disorder subclassified as mainly schizophrenic, however,
      were highest in the HRAff group. Rates of psychotic affective disorders did not
      differ between the HRSz and other groups. Age-corrected morbidity risks were
      similar to lifetime prevalence rates. Rates of the three cluster A personality
      disorders did not differ among the groups, but the combined rate was greater in
      the HRSz and HRAff groups than in the NC group. CONCLUSIONS: Our data strongly
      support a specific familial liability to narrowly defined schizophrenia that is
      not shared by families of probands with affective disorder. Schizoaffective
      disorder and cluster A personality disorders, however, occur in families of both
      schizophrenic probands and probands with affective disorder. Psychotic affective
      disorders, which are not increased in HRSz subjects, do not appear to be an
      expression of the liability to schizophrenia.

PMID- 7575108
TI  - Child and adolescent mental disorders and the search for an NIMH director. Quo
      Vadis?

PMID- 7575109
TI  - Clozapine-induced increase in plasma levels of soluble interleukin-2 receptors.

PMID- 7575110
TI  - Complicating factors in the analysis of acute drug-induced akathisia.

PMID- 7575111
TI  - Good news in the Greenvilles of America.

PMID- 7575112
TI  - The crime of saving lives. The FDA, John Najarian, and Minnesota ALG.
AB  - The indictment of John Najarian, MD, and Richard Condie at Minneapolis, Minn, on
      April 10, 1995, was a defining episode in the prolonged agony that has ensued
      since August 1992, when the federal Food and Drug Administration (FDA) placed
      Minnesota Anti-Lymphocyte Globulin (MALG) on clinical hold, bringing to an end
      its use as an immunosuppressive agent for patients undergoing transplantation.
      The principal charge in the indictment is that from about 1968 until 1992--the
      whole period of the development and use of MALG--Dr Najarian and Mr Condie
      conspired to defraud the United States by impeding the FDA in its oversight of
      biological drugs and that they did so for the purpose of financial gain. If the
      charges can be considered seriously, they mean that Dr Najarian's purpose in the
      development and manufacture of MALG was to make money, presumably for himself,
      and that the possible benefit of MALG to the patients was of secondary concern to
      him. Several difficulties arise immediately. In 1968, MALG offered a promising
      new approach to immunosuppression. In a relatively crude form, it had been used
      at the University of Colorado with striking improvement in the survival of
      patients undergoing transplantation and transplanted organs, but it was painful
      to administer by intramuscular injections and, in addition to other side effects,
      produced muscular spasms. Dr Najarian and his colleagues succeeded in purifying
      MALG so that the pure globulin could be injected into a central vein. The process
      of purification was complicated and expensive, so it was hardly practical for
      each transplant center to produce MALG for itself. Thus, in 1969, when Dr
      Najarian submitted an investigational new drug application (IND) to the FDA, he
      stated that his purpose was to manufacture MALG not only for patients at the
      University of Minnesota Hospital but also for patients at other transplant
      centers, which were not in a position to make it for themselves. He asked the FDA
      to approve recovery of the cost of providing MALG to other institutions. The FDA
      approved Dr Najarian's IND application early in 1970 but did not respond to his
      request for cost recovery--then, or for the next 15 years. Dr Najarian was free
      to manufacture MALG and to distribute it to other transplant centers for
      investigational use, but as for paying for it, that was his problem. The FDA
      offered no suggestion.

PMID- 7575113
TI  - Surgery for peptic ulcer in the Helicobacter pylori era.

PMID- 7575114
TI  - Direct observations of surgical wound infections at a comprehensive cancer
      center.
AB  - OBJECTIVES: To identify the rate of surgical site infection and risk factors for
      surgical site infection in patients with cancer and to evaluate antibiotic use
      patterns on surgical oncology services. DESIGN: Criterion standard. SETTING:
      Memorial Sloan-Kettering Cancer Center, a comprehensive cancer center at a
      university hospital. PATIENTS: Over a 15-month period, 1226 patients undergoing
      1283 surgical procedures performed by the Breast, Colorectal, and Gastric-Mixed
      Tumor surgical services. MAIN OUTCOME MEASURE: Direct observation of surgical
      sites was performed by a single, surgeon-trained member of the hospital's
      Infection Control Section, adhering to an established protocol for grading of the
      surgical site. RESULTS: Operative procedures accounted for the following
      traditional wound class distributions: class I (clean), 630 cases; class II
      (clean-contaminated), 577 cases; class III (contaminated), 29 cases; and class IV
      (dirty-infected), 47 cases. Surgical site infection rates were 3.8% in class I;
      8.8% in class II; 20.7% in class III; and 46.9% in class IV procedures. The mean
      (+/- SD) age was 57.7 +/- 14.3 years and the Anesthesiology Society of America
      physical assessment score, 2.3 +/- 0.7. The mean (+/- SD) operation time was 145
      +/- 104.9 minutes. Logistic regression analysis demonstrated several risk factors
      for surgical site infection: obesity (P < .0001); a contaminated or dirty
      infected surgical procedure category (P < .0001); operation time greater than 4
      hours (P = .0004); Anesthesiology Society of America physical assessment score of
      3 or greater (P < .01); and preoperative length of stay of 3 or more days (P =
      .03). CONCLUSIONS: Risk factors for surgical site infection in patients with
      cancer are similar to those found in the National Nosocomial Infections
      Surveillance System. However, as an individual risk factor among our patient
      population, obesity contributed as strongly as the surgical procedure category to
      a patient's likelihood of acquiring a surgical site infection. In addition to
      Anesthesiology Society of America status, length of the surgical procedure, and
      surgical procedure category, obesity should warrant consideration as an
      individual risk factor for surgical site infection.

PMID- 7575115
TI  - Cystic neoplasms of the pancreas. A clinicopathologic study, including DNA flow
      cytometry.
AB  - OBJECTIVE: To review the classification, clinical behavior, and appropriate
      therapy for cystic neoplasms of the pancreas. We examined patient demographics,
      clinical parameters, preoperative imaging modalities, histologic findings, and
      tumor DNA content to determine which best predict outcome. DESIGN: Case series
      and survey of pathologic specimens. SETTING: Tertiary care center. PATIENTS:
      Twenty-two patients with cystic neoplasms of the pancreas treated at affiliates
      of Northwestern University Medical School, Chicago, Ill. MAIN OUTCOME MEASURES:
      Predictive value of preoperative testing, tumor DNA content, patient survival.
      RESULTS: In 20 patients undergoing computed tomographic scan, the tumor was
      visualized in every case. All other imaging studies evaluated were less likely to
      demonstrate the lesion. Eight of 10 patients with serous cystadenomas were alive
      with no evidence of disease at the time of this report; one patient was alive
      with local recurrence, and a second patient had died of unrelated causes. All
      patients with mucinous cystadenomas were alive with no evidence of disease. Three
      of seven patients with cystadenocarcinomas had aneuploid, high S-phase tumors,
      and one had a diploid, high S-phase tumor; all four died (mean survival, 4.8
      months). Two patients with cystadenocarcinomas had diploid, low S-phase tumors;
      both were long-term survivors but died of their disease at 8.6 and 9.3 years.
      CONCLUSIONS: (1) Computed tomographic scan is the most valuable diagnostic
      imaging study for preoperative evaluation of these patients. (2) Precise
      preoperative determination of tumor type is not possible. (3) DNA flow cytometry
      may help identify patients with aggressive tumors who may benefit from adjuvant
      chemoradiation.

PMID- 7575116
TI  - The association between melanoma, lymphoma, and other primary neoplasms.
AB  - BACKGROUND AND OBJECTIVE: Reports of multiple primary tumors are not new.
      However, we have noted a disproportionate number of patients with melanoma in
      whom lymphoma develops and wanted to define the incidence of this association.
      DESIGN: All 664 patients with melanoma treated at Yale-New Haven Hospital, Conn,
      during the 5-year period from 1986 to 1991 were reviewed. The incidence of all
      the associated malignant neoplasms among our patients with melanoma was compared
      with the incidence that would be expected in the normal population adjusted for
      age, race, and sex. RESULTS: Among the 664 patients, 54 (8.1%) had one or more
      additional malignant neoplasms. Of the 10 different malignant tumor types
      recorded, lymphomas were the most prevalent. This incidence of lymphoma among the
      melanoma patients was 12 of 664, resulting in an incidence of 548 per 100,000
      population, 16 times higher (P < .0125) than the expected incidence (34 per
      100,000) when adjusted for age, sex, and race. CONCLUSIONS: The incidence of a
      second malignant neoplasm in our patients with melanoma was 8.1%. Lymphoma was a
      particularly common type of second malignancy, showing an incidence more than 16
      fold higher than that expected in the normal population. It is particularly
      important, from a clinical point of view, to be aware of this when clinically
      palpable lymph nodes develop in areas not normally the site of regional lymphatic
      drainage of the primary melanoma.

PMID- 7575117
TI  - Five-year follow-up after radical surgery for colorectal cancer. Results of a
      prospective randomized trial.
AB  - OBJECTIVE: To determine whether an intensified follow-up of patients with
      colorectal cancer can lead to improved reresectability and a better long-term
      survival. DESIGN: A prospective randomized trial of 106 patients. SETTING: Oulu
      University Hospital, a referral center in northern Finland. PATIENTS: A total of
      106 consecutive patients who underwent radical resection for colorectal cancer,
      54 of whom were randomized into a conventional follow-up group and 52 into an
      intensified follow-up group. MAIN OUTCOME MEASURES: After a 5-year follow-up, the
      time of detection of recurrence, the recurrence rates, the first method showing
      recurrence, the mode of recurrence, reresectability, and survival were compared
      between the groups. RESULTS: The recurrences were identified earlier in the
      intensified follow-up group than in the conventional follow-up group (mean +/-
      SD, 10 +/- 5 months vs 15 +/- 10 months). The overall recurrence rate was 41%,
      with 39% in the conventional group and 42% in the intensified group.
      Carcinoembryonic antigen determination was the most common method showing
      recurrence in both groups. Endoscopy and ultrasound were beneficial in the
      intensified follow-up group, but computed tomography failed to improve the
      diagnostics. The mode of recurrence did not differ between the groups. Radical
      resections were performed on 19% (8/43) of the patients, 14% (3/21) in the
      conventional group and 22% (5/22) in the intensified group. The cumulative 5-year
      survival was 54% in the conventional group and 59% in the intensified group.
      CONCLUSION: Earlier detection of recurrent colorectal cancer by intensified
      follow-up does not lead to either significantly increased reresectability or
      improved 5-year survival.

PMID- 7575118
TI  - Ultrasonographic characterization of hepatic cryolesions. An ex vivo study.
AB  - OBJECTIVE: To determine the physical basis for the ultrasonographic
      characteristics of the hepatic ice ball produced by cryotherapy and the size
      correlation between the actual hepatic ice ball and the ultrasonographic
      cryolesion. DESIGN: Experimental ex vivo study involving controlled freezing with
      liquid nitrogen recirculating probes of fresh porcine livers immersed in various
      solutions at ambient temperatures (20.2 degrees C to 22.6 degrees C), together
      with measurements of the impedance of frozen and unfrozen liver. RESULTS: First,
      the hyperechoic rim is caused by reflection of 34% of ultrasound waves at the
      interface between unfrozen and frozen liver as a consequence of an increased
      acoustic impedance of frozen liver that was calculated to be approximately 3.8
      times that of unfrozen liver tissue. The increased acoustic impedance is due to
      the decrease in elasticity of hepatic tissue as it freezes. Second, the posterior
      acoustic shadowing is partly due to the attenuation of the incident ultrasound
      waves by reflection at the interface between unfrozen and frozen liver. It is
      also dependent on the crystalloid-protein content of hepatic parenchyma, which
      ensures a homogeneous lesion by preventing "shattering" within the cryolesion.
      This is in sharp contrast to the ultrasonographic appearance of an ice ball
      formed in ionized water, in which the hyperechoic rim overlies an area of
      posterior acoustic enhancement. Third, the correlation of the size between the
      ultrasonographic cyrolesion and the measured hepatic ice ball approached unity (r
      = .99), and the two measurements were identical for cryolesions less than 50 mm
      in diameter. CONCLUSION: Ultrasound is an accurate method for depicting the
      actual diameter of frozen solid hepatic tissue in cryotherapy for liver tumors,
      but the present technology does not provide accurate assessments of the volume of
      frozen tissue.

PMID- 7575119
TI  - Intrahepatic cholangiocarcinoma. Results of aggressive surgical management.
AB  - OBJECTIVE: To report the results of a deliberately aggressive surgical management
      in patients with intrahepatic cholangiocarcinoma. DESIGN: A case series of
      patients with intrahepatic cholangiocarcinoma. SETTING: A tertiary care
      university hospital in a metropolitan area. PATIENTS: From 1989 to 1993, 19
      patients with intrahepatic cholangiocarcinoma underwent laparotomy, with a 74%
      resectability rate (14 liver resections). In addition, two selected patients with
      a slow-growing tumor underwent orthotopic liver transplantation after limited
      recurrence following resection in one case and after exploratory laparotomy in
      the other. INTERVENTIONS: The 14 liver resections included six right or left
      hepatectomies and eight extended right or left hepatectomies. Total vascular
      exclusion of the liver was used in nine cases (64%) and resection of the biliary
      confluence with reconstruction was used in six cases (43%). RESULTS: There was
      one postoperative death (7%). There were four postoperative biliary fistulas
      (28%). Overall actuarial 1- and 2-year survival rates were 58% and 32%,
      respectively. The 1- and 2-year survival rates were 100% after curative resection
      (no lymph node invasion, clearance margin of < or = 1 cm, and solitary tumor
      [five cases]) and 48% and 10% after palliative resection. Median survival was 14
      months for the whole series and 27 and 9 months following curative and palliative
      resections, respectively. The two liver transplant recipients are alive and free
      of disease at 25 and 31 months. CONCLUSION: These results support aggressive
      surgical management in patients with intrahepatic cholangiocarcinoma, including
      complex liver resection procedures and selective use of orthotopic liver
      transplantation.

PMID- 7575120
TI  - Systemic leakage and side effects of tumor necrosis factor alpha administered via
      isolated limb perfusion can be manipulated by flow rate adjustment.
AB  - BACKGROUND: The tolerated systemic dose of recombinant tumor necrosis factor
      alpha (rTNF-alpha) is very limited, since its administration leads to a severe
      septic shock-like condition. Its implementation in isolated limb perfusion (ILP)
      for metastatic melanoma or advanced soft-tissue sarcoma confined to the limb
      facilitates doses of rTNF-alpha 10 times higher than the systemic tolerated dose.
      However, with the traditional high flow rate used in ILP, systemic leakage and
      side effects are not eliminated. OBJECTIVE: To determine if a lower perfusion
      flow rate would reduce leakage and consequently toxic effects. METHODS: Isolated
      limb perfusion was performed for melanoma and soft-tissue sarcoma confined to the
      limb using a flow rate of 869 +/- 122 mL/min in nine patients (group 1) and a
      lower rate of 286 +/- 62 mL/min in six patients (group 2). RESULTS: The systemic
      leakage rate was 12.5% +/- 2.9% in group 1, compared with 2.3% +/- 1.0% in group
      2 (P = .003). Peak TNF-alpha levels were 29,000 +/- 2700 pg/mL in group 1, higher
      than 1580 +/- 1355 pg/mL in group 2 (P = .02). The tachycardia, hypotension,
      increased cardiac output, decreased systemic vascular resistance, bilirubinemia,
      elevation of liver enzyme levels, hypocholestrolemia, thrombocytopenia, and
      prolongation of prothrombin and partial thromboplastin times all observed in
      group 1 were significantly attenuated or eliminated in group 2. The limb PO2,
      PCO2, pH, and viability remained similar in both groups. Also, the tumor response
      rate remained high and was unaffected by the decrease in flow rate. CONCLUSIONS:
      Decreasing perfusion flow rate during ILP results in diminished leakage of TNF
      alpha. Consequently, the systemic hemodynamic, metabolic, and hematologic toxic
      effects are virtually abolished.

PMID- 7575121
TI  - Dopamine compensates for deterioration of hepatic hemodynamics and metabolism
      during occlusion and reperfusion of the hepatic artery.
AB  - OBJECTIVE: To investigate the effects of temporary hepatic arterial occlusion and
      dopamine on hepatic hemodynamics and metabolism. DESIGN: Experimental animal
      study in a dog model. The proper hepatic artery was occluded for 60 minutes;
      then, it was reperfused for 60 minutes. Hepatic hemodynamic and oxygen metabolic
      values, lactate uptake ratios, and blood glucose levels were determined
      repeatedly throughout the experiment. Data are given as mean +/- SE.
      INTERVENTION: In another group, dopamine hydrochloride, 10 micrograms/kg per
      minute, was infused intravenously throughout the experiment, and the same
      variables were recorded. RESULTS: Portal vein blood flow continuously decreased
      during occlusion, and it decreased even further after declamping of the hepatic
      artery; this led to a disturbance of oxygen and lactate metabolism in the control
      group. Dopamine increased the portal vein blood flow from 84.9% +/- 3.9% to
      100.9% +/- 3.6% of the preocclusion levels after 60-minute occlusion and from
      79.0% +/- 3.6% to 93.6% +/- 5.1% of the preocclusion levels after 60-minute
      reperfusion (P < .05, respectively). Dopamine also enhanced the hepatic oxygen
      uptake ratio from 112.8% +/- 12.0% to 150.7% +/- 11.6% of the preocclusion levels
      after 60-minute reperfusion (P < .05, respectively). These factors contributed to
      acceleration of the hepatic oxygen consumption and lactate uptake ratio in the
      group of dogs that were infused with dopamine. CONCLUSIONS: Temporary occlusion
      of the hepatic artery causes deterioration of hepatic hemodynamics and
      metabolism. Administration of dopamine is an effective way to support hepatic
      function during occlusion of the hepatic artery.

PMID- 7575122
TI  - Hepatic segmentectomy for curative resection of primary hepatocellular carcinoma.
AB  - OBJECTIVES: To evaluate the feasibility and results of segmentectomy for curative
      resection of hepatocellular carcinoma and to compare the clinicopathological
      findings of the patients according to the tumor location in the liver. DESIGN:
      Case series. SETTING: A tertiary care center. PATIENTS: Seventy-five patients
      with Child's grade A or B liver function who had hepatocellular carcinoma that
      was confined to one segment and who underwent segmentectomy for curative
      resection of the tumor. The patients were divided into four groups: group P
      (posterior segmentectomy, n = 23); group A (anterior segmentectomy, n = 10);
      group M (medial segmentectomy, n = 16); and group L (lateral segmentectomy, n =
      26). MAIN OUTCOME MEASURE: Disease-free survival rate. RESULTS: Seventy-three
      percent of the patients had cirrhosis of the liver. The surgical mortality and
      morbidity rates were 5.3% and 36.0%, respectively. The 1-, 3-, and 5-year disease
      free survival rates were 61.9%, 39.1%, and 26.3%, respectively, and were not
      significantly different among the four groups (P = .86). Group L had the least
      operative blood loss and shortest operative time when compared with the other
      three groups (P < .05). The postoperative liver function changes were mild and
      transient in the four groups of patients. With regard to pathological factors,
      only tumor size differed among the groups (tumors in group L were significantly
      larger than those in the other three groups, P < .05). Forty-three percent of the
      recurrent tumors were solitary in the early stage, with 81% involving the
      segment(s) adjacent to the resected one and 57% being confined solely to the
      segment adjacent to the resected segment. Patients having recurrent
      hepatocellular carcinomas had significantly larger tumors at the time of
      resection than did those without recurrence (P = .03). CONCLUSIONS: Hepatic
      segmentectomy is an effective therapeutic approach for small hepatocellular
      carcinomas and can be done safely even in patients with chronic liver disease and
      impaired liver function.

PMID- 7575124
TI  - Retroperitoneal sarcomas and their management.
AB  - BACKGROUND: Retroperitoneal sarcomas historically have presented difficulties in
      their management due to a high rate of unresectability. OBJECTIVE: To determine
      prognostic parameters, resectability, and survival of these patients in a more
      recent period. DESIGN: Retrospective review, with a mean follow-up of 47 months.
      SETTING: Tertiary care cancer institute. PATIENTS: The charts of 90 consecutive
      patients with retroperitoneal sarcomas treated in the period from 1977 to 1995.
      No patient referred with a localized retroperitoneal sarcoma was excluded from
      this review. RESULTS: The resectability rate was 100% for the primary tumors (n =
      57) and 88% for the tumors initially presenting as local recurrence (n = 33). The
      5-year survival rate was 63% (66% for patients with primary tumors and 57% for
      those with local recurrence). The 10-year survival rate was 46% (57% for patients
      with primary tumors and 26% for those referred with local recurrence). The local
      recurrence rate was 25% for primary tumors and 39% for tumors initially presented
      as local recurrence (overall rate, 30%); it was 56% after local excision and 16%
      after wide or radical resection (P < .001). The 5- and 10-year survival rates
      were 72% and 61%, respectively, for those with wide resection and 55% and 23%,
      respectively, for those with local excision (P = .01). CONCLUSIONS: With modern
      surgical techniques, the overall resectability rate of retroperitoneal sarcomas
      is 96%. The ensuing survival, affected significantly by the histologic grade,
      approaches that for the extremity sarcomas.

PMID- 7575123
TI  - Photodynamic therapy. Cytotoxicity of aluminum phthalocyanine on intimal
      hyperplasia.
AB  - OBJECTIVE: To study the cytotoxic effect of photodynamic therapy (PDT) on
      myointimal hyperplasia (MIH) in 120 New Zealand white rabbits using the
      chromophore chloroaluminum phthalocyanine tetrasulfonate (APtS). DESIGN: A common
      carotid artery (CCA) injury model was used to initiate MIH. Photodynamic therapy
      was administered 1 week after injury (inhibition arm) or 6 weeks after injury
      (treatment arm). The inhibition arm CCAs were harvested 6 weeks after therapy.
      The treatment arm CCAs were harvested 1 week or 6 weeks after therapy. Each
      evaluation included four subgroups (n = 10 each): control, drug only, laser only,
      and drug plus laser. INTERVENTIONS: An established CCA balloon injury model was
      used. Photodynamic therapy was administered by exposing CCAs to continuous
      external laser irradiation 30 minutes after treatment with a 2.5-mg/kg
      intravenous dose of APtS (fluence = 25 J/cm2, lambda = 672 nm). The control and
      drug-only subgroups received sham reoperations without laser exposure. MAIN
      OUTCOME MEASURES: Following harvest, the CCAs were evaluated for area of stenosis
      and cell density. RESULTS: In the inhibition arm, no PDT effect was seen on
      intimal cell density or area stenosis. In the treatment arm, intimal cell density
      was markedly diminished (P < .05) in the rabbits in the drug-laser group that
      were killed 1 week but not 6 weeks after PDT compared with rabbits in the
      control, drug-only, and laser-only groups. Area stenosis was not significantly
      affected by PDT. CONCLUSIONS: Marked acute cytotoxicity of PDT on MIH was
      verified in vivo in the treatment arm. No sustained benefit of PDT was seen in
      the inhibition or the treatment arms. Refinements in dosimetry will be necessary
      to achieve long-term benefit of PDT for MIH.

PMID- 7575125
TI  - Comparative evaluation of contact ultrasonography and transcystic cholangiography
      during laparoscopic cholecystectomy: a prospective study.
AB  - BACKGROUND: The role of intraoperative cholangiography (IOC) during laparoscopic
      cholecystectomy (LC) is controversial. While many advocate its routine use,
      others argue for a selective approach. Recent reports showed laparoscopic contact
      ultrasonography (LCU) as a viable alternative to IOC. However, no prospective
      data were available to compare the accuracy, efficacy, and safety of the two
      diagnostic procedures. OBJECTIVE: To evaluate the benefits and disadvantages of
      LCU and IOC during LC. METHODS: Seventy-eight patients who underwent LC at Pisa
      (Italy) and Dundee (Scotland) university hospitals were entered in a prospective
      data registry. Details of operative technique and results of LCU and IOC were
      analyzed by reviewing videotape recordings of each procedure. RESULTS:
      Laparoscopic cholecystectomy was achieved in 73 patients, with five requiring
      conversion to the open procedure. The success rate of IOC was 90% (64/71).
      Performance of IOC demanded more than twice the time needed for LCU. Eleven
      percent (8/71) of cholangiograms were abnormal, with a false-positive rate of 1%
      (1/71). Laparoscopic contact ultrasonography detected all four instances of
      unsuspected ductal stones but none of the three cases of anomalous biliary
      anatomy. Clinically relevant incidental findings were picked up by LCU in six
      patients. CONCLUSIONS: Laparoscopic contact ultrasonography proved to be
      extremely accurate in the detection of ductal stones but less reliable in the
      disclosure of anomalous biliary anatomy. The essential role of IOC in providing a
      clear spatial display of the biliary tract was confirmed. Since the two
      procedures are complementary, their combined use is advisable in difficult LC to
      avoid retained common bile duct stones and prevent iatrogenic complications.

PMID- 7575127
TI  - Bile duct injuries during laparoscopic cholecystectomy. Factors that influence
      the results of treatment.
AB  - OBJECTIVE: To analyze the treatment of bile duct injuries during laparoscopic
      cholecystectomy to discern the factors affecting outcome. DESIGN: An analysis of
      the treatment of 88 patients with laparoscopic bile duct injuries. SETTING: A
      university hospital. PATIENTS: Eighty-eight patients with major bile duct
      injuries following laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Success
      of treatment, morbidity rate, mortality rate, and length of illness. RESULTS:
      Operations to repair bile duct injuries were unsuccessful in 27 (96%) of 28
      procedures when cholangiograms were not obtained preoperatively, and they were
      unsuccessful in 69% when cholangiographic data were incomplete. In some cases,
      lack of complete cholangiographic information led to an inappropriate and harmful
      operation. When cholangiographic data were complete, the first repair was
      successful in 16 (84%) of 19 patients. A primary end-to-end repair over a T tube
      (13 patients) was unsuccessful in every case in which the duct had been divided.
      Direct closure of a partial defect in the duct was successful in four of seven
      patients. Fifty-four (63%) of 84 Roux-en-Y hepaticojejunostomies were successful.
      Factors responsible for the unsuccessful outcomes were the following: incomplete
      excision of the scarred duct, use of nonabsorbable suture material, use of two
      layer anastomosis, and failure to eradicate subhepatic infection before the
      attempted repair. Dilatation and stenting was uniformly unsuccessful as primary
      treatment (three patients) and was unsuccessful in only seven of 26 patients
      following a previous operative repair. Patients first treated by the primary
      surgeon had an average length of illness of 222 days (P < .01). Only 17% of
      primary repair attempts and no secondary repair attempts performed by the
      laparoscopic surgeon were successful. Patients whose first repair was performed
      by tertiary care biliary surgeons had a length of illness of 78 days (P < .01),
      and 45 (94%) of 48 repairs by tertiary care biliary surgeons were successful.
      CONCLUSIONS: Surgeons who specialize in the repair of bile duct injuries achieve
      much better results than those with less experience. The worse results of other
      surgeons could be attributed in many instances to specific correctable errors.
      Nonsurgical treatment was usually unsuccessful and substantially increased the
      duration of disability.

PMID- 7575126
TI  - Growth hormone and insulinlike growth factor I enhance host defense in a murine
      sepsis model.
AB  - OBJECTIVE: To investigate the effects of exogenous growth hormone (GH) and
      insulinlike growth factor I (IGF-I) on host defense and survival in a murine
      model of Escherichia coli sepsis. DESIGN: Prospective randomized experimental
      trials. SETTING: Laboratory. MATERIALS: Nine-week-old female BALB/c mice.
      INTERVENTIONS: Mice were injected subcutaneously with 4.8 or 0.48 mg/kg of body
      weight per day of GH, 24 or 2.4 mg/kg of body weight per day of IGF-I or, as a
      control, normal saline solution, for 6 days. Mice were then challenged
      intraperitoneally with 1 x 10(8) colony-forming units per body of E coli. MAIN
      OUTCOME MEASURES: Fifty mice were observed for survival. In the next experiments,
      samples from the high-dose GH, high-dose IGF-I, and saline control groups were
      harvested before or at 4 or 6 hours after challenge. Numbers of peritoneal
      exudative cells and tissue-viable bacterial counts were determined. Peritoneal
      exudative cells were cultured with lipopolysaccharide (10 micrograms/mL) for 24
      hours. Levels of tumor necrosis factor, interleukin-1, and interleukin-6 in the
      peritoneal lavage fluid, plasma and supernatants of peritoneal exudative cell
      culture were measured. RESULTS: Both high and low doses of GH and high-dose IGF-I
      significantly prolonged survival. Growth hormone and IGF-I significantly
      increased peritoneal exudative cell numbers and reduced viable bacterial counts
      in the peritoneal lavage fluid and the liver. These hormones significantly
      suppressed excessive systemic cytokine production, while enhancing in vitro
      cytokine production and preserving local cytokine responses. CONCLUSION: The
      immunomodulation produced by administration of GH or IGF-I leads to improved host
      defense in this murine model of E coli sepsis.

PMID- 7575128
TI  - The commemoration of surgical teachers.
AB  - This address was given at a biennial meeting of the Michael E. DeBakey
      International Surgical Society. Surgical teachers are commemorated by the
      imitation of their pupils in accord with the human tendency to model ourselves
      after our heroes. The modeling is not merely a search for technical mastery but
      an emulation of virtues beyond the purely scientific. The lecture addresses the
      nature of teachers and teaching, the role of teachers as exemplars or heroes, the
      reasons why we commemorate certain teachers, and finally, the personal
      recollection of virtues, such as compassion, that make surgeons memorable for
      their pupils and patients. Citations from Thomas Carlyle, Jacques Barzun, and
      William Bennett illustrate the role of heroes, the nature of teaching, and the
      importance of virtue. Lessons are drawn from the lives of John Hunter and William
      S. Halsted, and from the work of the DeBakey family in surgery and in the craft
      of medical writing.

PMID- 7575129
TI  - A surgical subspecialist enhances general surgical operative experience.
AB  - OBJECTIVE: To examine the impact of a surgical subspecialist on residents'
      operative experience in a mature general surgery training program. METHODS:
      American Board of Surgery operative experience records were used to examine the
      impact of a surgical subspecialist on surgical training in a stable residency
      program. Operations performed as surgeon by residents in their chief and junior
      years were analyzed 4 years before and 4 years after the addition of this
      subspecialist to the faculty. Hospital admissions for Crohn's disease and
      ulcerative colitis during these periods were analyzed as well. RESULTS: There was
      a statistically significant increase in the number of ileal pouch anal
      anastomoses, ileostomies, small-bowel resections, partial colectomies, and
      coloanal anastomoses performed by surgical residents after the addition of a
      colorectal surgical subspecialist. CONCLUSIONS: Subspecialty faculty may
      favorably influence general surgical training by increasing resident operative
      experience and patient management skills with procedures characteristic of the
      subspecialty.

PMID- 7575130
TI  - Aberrant biliopancreatic duct. A probable cause of acute pancreatitis?
AB  - Abnormal biliopancreatic ducts are very uncommon in adults with the exception of
      those associated with abnormalities of either the pancreatic or the bile ducts.
      The case presented herein is unique in that a biliopancreatic connection occurred
      proximal to the papilla of Vater and the patient was symptomatic because of the
      aberrant connection. The surgical therapy consisted of cholecystectomy and
      ligation of the aberrant duct, with complete relief of severe, debilitating
      symptoms. This interesting clinical observation is discussed in the light of
      Opie's theory of biliary reflux into the pancreatic duct as a pathogenetic
      mechanism for acute pancreatitis.

PMID- 7575131
TI  - [Chemiluminescence assays for cytokines in serum: influence of age, smoking, and
      race in healthy subjects].
AB  - Evidence is accumulating that cytokines are important intermediates in the
      pathogenesis of many diseases such as asthma and pulmonary fibrosis. However, a
      major limitation to clinical studies of cytokines has been the inability to
      measure these important biomarkers in serum from normal, healthy controls.
      Without this capability, interpretation of apparently elevated levels in
      problematic, and evaluation of diseased level is impossible. We have recently
      developed chemiluminescence ELISA (CL-ELISA), resulting in a 100-fold increase in
      sensitivity. To assess the influence of age, smoking, and race on serum cytokine
      levels in healthy population, we measured IL-4, 5, 6, 10, IFN-gamma, and GM-CSF
      in serum of healthy Japanese (n = 38), and Americans (n = 10) using CL-ELISA. In
      this small population with narrow age range, no difference between smokers and
      nonsmokers was found for any cytokine. No correlations between age and cytokines
      was demonstrated. However, Japanese samples had lower levels of IL-4, 5, and 10
      than American samples. Further evaluation using more controlled study design and
      larger populations will be necessary to determine whether this difference is due
      to inherent racial differences in Th2 cell function.

PMID- 7575132
TI  - [Airborne Japanese cedar allergens studied by immunoblotting technique using anti
      Cry j I monoclonal antibody--comparison with actual pollen counts and effect of
      wind speed and directions].
AB  - We collected airborne particles of Japanese cedar pollen with Burkard's sampling
      tape in Toyama from February to April 1992. The tape was cut into two pieces in
      parallel to time axis. The one of piece of the tapes was stained with glycerin
      jerry and stained pollens were counted with a microscope. The other piece was
      treated according to the immunoblotting technique. The airborne pollen allergens,
      reacting with anti-Cry j I monoclonal antibody, were stained as blue spots. The
      spots were classified by diameter into two groups, large spots (> 50 microns) and
      small spots (< 50 microns). There were significant correlations found between the
      airborne Cry j I allergen spots (in large and small) and actual pollen counts
      obtained with the Burkard's sampler and the Durham's sampler (r = 0.729, 0.586 in
      large spots and r = 0.676, 0.489 in small spots, p < 0.001). The counts of small
      spots stayed in high level even in April when actual pollen counts decreased. We
      concluded that this discrepancy was caused by allergenic crushed cedar pollen
      particles staying floating longer than actual pollens. Secondly we set a gauge of
      wind speed and direction at the same point as the samplers. The actual pollen
      counts and large spots counts were significantly larger in the wind (SE wind in
      Toyama city) from cedar trees blooming area than other areas. However small spots
      counts did not differ significantly according to wind directions. Wind speed did
      not effect on actual pollen counts, large spots counts and small spots count.

PMID- 7575133
TI  - [Effects of inhaled beclomethasone on height growth and bone metabolism in
      children with asthma].
AB  - To evaluate the influences of inhaled beclomethasone dipropionate (BDP), 7.3-30.9
      (15.5 +/- 6.5) micrograms/kg/day, on bone metabolism and height growth, we
      performed a longitudinal study for 6 months in 34 children with asthma aged
      between 3 and 15 years. Bone mineral density estimated by digital image
      processing method (DIP) and serum level of osteocalcin did not show any
      significant change, but height growth was slightly suppressed in the patients who
      inhaled more than 15 micrograms/kg/day of BDP. We concluded that the decision to
      prescribe inhaled BDP should be made on the balance of the clinical effects and
      the improvement of quality of life against the possibility of side effects.

PMID- 7575134
TI  - [Effect of dosing schedule on efficacy of corticosteroid inhalation in chronic
      asthma].
AB  - A randomized study was conducted for 4 weeks to evaluate the effect of twice
      daily inhalation of beclomethasone dipropionate (BDP) inhalation (group A) as
      compared to four times a day inhalation (group B) in chronic asthma. Patients
      were randomly allocated to receive BDP at a dosage of eight puffs twice daily
      (800 micrograms/day, group A) or four puffs four times daily (800 micrograms/day,
      group B). Forty four patients entered the study but eleven were excluded because
      of their insufficient records or unfitness to eligibility criteria. There was no
      significant difference in patients' characteristics such as types, and severity
      of diseases between the two groups. Daily keeping of symptom scores, twice daily
      measurement of morning and night peak expiratory flow (PEF) and checking of the
      drug consumption were performed throughout the study. There was no significant
      difference in the mean %PEF either at 2 and 4 weeks at the study between the two
      groups. Symptom scores, asthmatic scores, bronchial hyperresponsiveness,
      pulmonary function tests (FVC, FEV1, FEV1%) and serum cortisol levels also showed
      no significant difference between the two groups. These results indicate that
      twice daily inhalation of BDP (800 micrograms/day) for four weeks caused the same
      effects on the patients with chronic bronchial asthma as 4 times daily inhalation
      did. Therefore, twice daily inhalation therapy with BDP is recommended for
      chronic bronchial asthma patients.

PMID- 7575135
TI  - [Desensitization immunotherapy on patients with mite-positive bronchial asthma
      using purified mite feces antigen fractions].
AB  - At present, we are performing desensitization immunotherapy on patients with mite
      positive bronchial asthma using purified mite feces antigen fractions. We
      obtained the following results in 13 patients 4 to 12 months after the start of
      treatment. 1) The fraction showing the maximum reaction in the skin test was HM1
      2 (molecular weight: 150-155 kD) in two patients, HM2 (30-40 kD) in nine patients
      and HM3 (10-20 kD) in two patients, and immunotherapy was performed using these
      fractions. None of the patients showed the maximum skin reactions or was treated
      with HM4 (less than 10 kD). 2) In nine patients with perennial asthma, the
      effects of treatment were excellent in four and moderate in three, while two
      cases remained unchanged. In four patients with seasonal asthma, the treatment
      was effective in all cases. 3) In patients in whom immunotherapy was effective,
      specific IgG antibody increased after the treatment, but it did not increase in
      the unchanged cases. Among the subclasses of specific IgG antibody increased by
      the treatment, no clear changes were seen in IgG4 antibody and no conclusion has
      been reached at present. 4) None of the patients had definite adverse reactions
      such as the occurrence of asthma attacks or anaphylaxis. These results suggested
      that purified mite feces antigens are safe and effective. We plan to continue
      this study with more patients in the future.

PMID- 7575137
TI  - [An adult case of rice-induced asthma with aspirin idiosyncrasy].

PMID- 7575136
TI  - [Effect of BAY u3405-thromboxane A2 receptor antagonist, on biphasic airway
      responses induced by platelet-activating factor in actively sensitized guinea
      pigs].
AB  - Our previous study in activity sensitized guinea pigs demonstrated an LAR-like
      increase in respiratory resistance (Rrs) at 3 to 9 hr after PAF inhalation. The
      result suggested possible involvement of the priming effect of active
      sensitization and PAF. Mean while, thromboxane A2 (TXA2) is known to be induced
      by PAF. The present study investigated the involvement of TXA2 in the guinea pig
      LAR model with a new TXA2 receptor antagonist, BAY u3405. One hr after BAY u3405
      administration to guinea pigs sensitized by ovalbumin, the Rrs following
      inhalation of PAF was subsequently determined. Infiltration of inflammatory cells
      in the airway tissue 9 hr after PAF inhalation was also observed. While a re
      increase in Rrs was found in all the cases in the control group, the re-increase
      in Rrs was inhibited significantly in the BAY u3405 administration group, 4 to 9
      hr after PAF inhalation. The numbers of eosinophils and lymphocytes in the airway
      tissue were significantly decreased in the BAY u3405 administration group, as
      compared with the control group. From these results, the possibility is suggested
      that TXA2 and its direct effect on the airway and the migration-enhancing effect
      on eosinophils and T lymphocytes, as well as PFA, are involved in the development
      of LAR by PAF.

PMID- 7575138
TI  - [A case of interstitial pneumonia with chronic hepatitis C following interferon
      alfa and sho-saiko-to therapy].

PMID- 7575139
TI  - [RANTES expression on human bronchial epithelial cells].
AB  - Viral infection induces airway inflammation. It is possible that bronchial
      epithelium derived chemokine contributes to the migration and accumulation of
      inflammatory cells in the airway viral infection. We infected bronchial
      epithelial cells with influenza virus and analysed mRNA expression and production
      of RANTES. The expression of mRNA and the production of RANTES were detected in
      infected cells using RT-PCR method and ELISA.

PMID- 7575140
TI  - The relationship between health status, motivation and work efficiency of forest
      workers.
AB  - The influence of psychological factors on the health status and work efficiency
      was investigated in a sample of 909 forest workers whose typical diseases had
      been previously defined. Data concerning the motivation for work were taken
      during obligatory medical tests. Medical variables (health status, diagnoses,
      number of diagnoses per worker), psychological variables (job satisfaction, wish
      to change the job), and work-related variables (fulfillment of job norms) were
      used. Hypotheses of the relationship between the selected pairs od variables were
      tested by contingency tables. The lifetime trends of each variable were modelled
      by means of linear functions. The presumed influence was confirmed by the results
      obtained. Negative motivation appeared to be a very significant factor of the
      forest workers' health status and their work efficiency.

PMID- 7575141
TI  - Evaluation of physical exertion by statistical analysis of worker's heart rate at
      log skidding.
AB  - Results of investigation into the physical exertion of the log skidding workers:
      tractor driver, winch operator and choker are presented. The investigation
      consisted of laboratory and field measurements and included measurements of the
      heart rate and assessment of the work effect, the work time structure, and the
      worker's physical exertion and energy consumption. According to the average rate
      during daily work, the physical exertion of the tractor driver and winch operator
      was classified as low exertion (75-95 min-1), whereas that of the choker was
      established as medium exertion (96-115 min-1). Energy consumption was calculated
      for the daily working time of 262 minutes, according to field measurements and
      for normal eight-hour work. According to field measurement values the tractor
      driver's and winch operator's work was categorized as light work (1.23-2.51 MJ)
      and that of the choker as heavy work (2.52-6.30 MJ). According to the values for
      eight-hour work, the tractor driver's and the winch operator's jobs were
      classified as heavy work (2.52-6.30 MJ/8 h) and the choker's job as the heaviest
      (6.31-10.47 MJ/8 h).

PMID- 7575142
TI  - Hand transmitted vibrations caused by orbital hand sanding machines.
AB  - The paper reports and analyses results of vibration measurement carried out on
      orbital hand sanding machines. Vibrations were measured on the front and rear
      handles of the FESTO LRB-W1 and LRB-T1 orbital hand sanding machines and at two
      points on the holding handle of the FESTO RTL-F1 hand sanding machine. The
      measured levels of the weighted vibration accelerations were compared to the
      daily exposure limits according to ISO 5349, ISO/TC 108/SC4/14 and NF E90-402.
      Daily exposures for each type of sanding machine were determined according to the
      same standards.

PMID- 7575143
TI  - Measurement of the airborne noise and the noise at the operator's position
      emitted by the ECOTRAC V-1033 F forest tractor.
AB  - The paper reports on the measurement procedure and results of measurements of the
      airborne noise emitted by the ECOTRAC V-1033 F forest tractor. The measurements
      were carried out in accordance with the International Standards ISO 4872 and 362
      for the stationary test condition. The paper further reports on noise
      measurements at the tractor operator's position conducted in accordance with the
      International Standards ISO 5131 and 6394. All measurements were performed using
      the Bruel & Kjaer 4165 type microphone and the 2209 type sound level meter from
      the same manufacturer. According to ISO 4872, 6393 and 362 the noise level did
      not exceed the limit values. However, the noise level at the operator's position
      at full load and at nominal load exceeded the limits. Measures to be undertaken
      should aim at protecting the driver and improving the cab characteristics.

PMID- 7575144
TI  - Noise and vibration load of lumbermen.
AB  - At eight lumbering sites in Slovenia the noise load of lumbermen working with new
      and used motor saws was investigated by noise measurements at the ear level. A
      major contribution to the noise load (Leqv = 96-100 dB(A) came from motor saw
      operations such as limbing. Lumbermen are overloaded with interrupted noise for
      25 per cent of their working time. The noise produced by a used motor saw exceeds
      the noise coming from a new one by 0.7 dB(A). Results of a pilot research into
      the lumbermen's vibration load generated by Husqvarna 266 and 254 motor saws are
      also presented. The measurements involved three cutting sites and four lumbermen
      for six days. The vibration load during the working hours ranged between 6.6 and
      10.8 m/s-2. Owing to the fact that vibrations are interrupted and the exposure
      does not last throughout the working day, the vibration load does not reach a
      level which would be detrimental to lumbermen's health.

PMID- 7575145
TI  - [Man and forestry work--a chronologic perspective].
AB  - Forest work has been an object of systematic research for two centuries. The
      research includes studies of work methods and techniques, ergonomic aspects,
      field conditions, productivity, health problems, work safety, remuneration,
      psychological and sociological aspects of forest labour. Research in forest work
      originated in Central Europe but has since spread to all parts of the world.
      Viewing man and forest work from the 19th to the 21st centuries we can conclude
      the following: Until the mid-19th century forest work was carried out by human
      and animal power, aided by the force of gravity, water and wind. For man, it was
      one of the most difficult and dangerous jobs. Forest work demanded a large number
      of workers. The mid-1800s saw the beginning of mechanization of hard load motion
      in wood transportation. The mechanization of forest work is constantly
      increasing. Versatile multi-functional machines are introduced into various
      segments of forest work. Today, there is a wide range of work methods and
      techniques in forestry. At the same time, side by side, one can see forest
      operations performed entirely by human power and others, mechanized and fully
      automated. With the development of new work methods and techniques, and new
      forest products, the need for man's physical labour gives way to an increasing
      demand for general knowledge and expertise. Powerful, multi-functional machines,
      supported by information technology and operated by highly qualified
      professionals have stretched the limits of the sources of work energy and
      information flow in performance and optimization of forest work.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7575146
TI  - [Stress on the lumbar spine in workers in the beer brewing industry].
AB  - The appearance of lumbal syndrome was analysed in two groups of workers in the
      "Zagrebacka pivovara" brewery. In a group of 23 workers whose mean age was 34
      years and mean length of service 12 years, nine (39.1%) suffered from lumbal
      syndrome. In another group of 33 workers, with the mean age of 31 years and the
      mean length of service of nine years there were 24 (72.7%) suffering from the
      syndrome. According to Student's t-test the differences in age and length of
      service between the two groups were not significant (P > 0.05), but the
      difference in the number of ill was significant (P < 0.05). Analysis of the
      workplace showed that a heavy burden of the lumbal spine was involved, especially
      with the workers from the second group, and that ergonomic solutions were
      necessary.

PMID- 7575147
TI  - [The cervicobrachial syndrome in women in the metal-working industry].
AB  - All metal workers from a metal-working industry (eight women) who operated
      pressing, cutting and boring machines were found to have cervicobrachial
      syndrome. Their job involved forced-sitting body posture and repetitive
      movements. These are particularly important risk factors at the workplace for the
      occurrence and development of cervicobrachial syndrome. The workers demanded
      medical assistance at 12 years of work and an average age of 32.1 years. The
      working chair of poor ergonomic design was established as a major cause of the
      early occurrence of cervicobrachial syndrome.

PMID- 7575148
TI  - [The ergonomic approach to vocational guidance and selection].
AB  - The paper deals with the results of health examinations of elementary school
      children--eight graders carried out within the programme of vocational guidance
      in an area of Croatia (the period 1991-1993). The expert's evaluation showed that
      out of a total of 1983 pupils examined 855 had health disturbances or functional
      impairments that required properly oriented further vocational training. Advice
      concerning the choice of school was based on the anticipated requirements and
      ergonomic characteristics of the pupils future job and their psychophysical
      abilities. Proper vocational guidance avoids the need for later selection, which
      is always a complicated problem. This is illustrated by two documented examples.

PMID- 7575149
TI  - [Ergonomic problems in the textile industry].
AB  - Practical problems from the point of view of ergonomic requirements at workplaces
      in the textile industry are presented. Health impairments are discussed as
      possible consequences of poor working conditions. Ergonomic solutions for a
      number of work operations have been proposed. It has been stressed, however, that
      with the technology currently in use great improvement cannot be expected in this
      branch of industry in the near future.

PMID- 7575150
TI  - [Improper body posture of bus drivers].
AB  - The role of bus transport in the city and intercity traffic, the development of
      bus transport and the consequences of the driver's unsuitable body position upon
      health are dealt with. Buses make 0.4-0.5% of the total number of registered
      motor-driven vehicles. Of the total number of traffic accidents caused by motor
      vehicle drivers in Croatia those due to bus drivers come to 1.9-2.2%. The bus
      driver's tasks, working conditions, work environment and other characteristic job
      related activities are discussed. Special emphasis is given to the driver's
      unsuitable body posture and to the ergonomic requirements of the driver's seat.
      Investigations show the unsuitable posture to be cause of health disorders. The
      most common are diseases of circulation (especially arterial hypertension),
      locomotor system diseases (back pain syndrome) and psychic disorders.

PMID- 7575151
TI  - [The forestry work environment and its ergonomic requirements].
AB  - The paper describes chief instruments of forest production and their ergonomic
      requirements. The level of mechanization in the forestry production differs from
      high in logging and roadbuilding to a considerably lower one in silviculture,
      where nursery production stands out with the level of mechanization equalling
      that of agriculture. Ergonomic requirements greatly depend on the attitude of a
      particular social environment towards work safety. Some ergonomic requirements
      take the form of standards, recommendations or agreements. The chain saw is
      characterized not only by ergonomic-technical properties but also by mass, noise
      and vibration. Over the past three and a half decades, each of these parameters
      has come to conform to stricter and stricter requirements. Mass has been reduced
      to less than 8 kg, noise near the cutter's ear to about 100 dB(A), and the
      estimated acceleration transfer to the hand/arm system (WAS) below 12.5 m/s2
      (frequently even below 10 m/s2).

PMID- 7575152
TI  - [Is treatment of hypercholesterolemia able to reduce total mortality?].

PMID- 7575153
TI  - [Esophageal origin of precordial pain in chagasic patients with normal
      subepicardial coronary arteries].
AB  - PURPOSE: To study the chest pain of esophageal origin in chagasic patients (CH)
      and non-chagasic subjects (NCH) with normal coronary arteries. METHODS: The study
      comprised 48 patients: 33 CH (age 56 years, 50% male) and 15 NCH (age 47 years,
      25 male), with precordial chest pain and normal subepicardial coronary arteries.
      They were assigned to upper digestive tract radiologic and endoscopic study,
      esophageal manometric evaluation at baseline and after provocative tests
      (Bernstein and intravenous edrophonium). RESULTS: Radiologic study: 14 (42%) CH
      and 4 (27%) NCH had esophageal dilation (p > 0.05). Hiatal hernia was documented
      in 7 (21%) CH and 6 (40%) NCH (p > 0.05). 2) Digestive endoscopy: In 15 (45%) CH
      and 6 (40%) NCH distal esophagitis were seen. In the NCH, esophagitis occurred
      with hiatal hernia; however only 30% of CH with esophagitis had also hiatal
      hernia while another 30% had esophageal dilation. 3) Esophageal motility
      disorders (EMD): 11 (33%) CH showed EMD: 8 with inferior esophageal sphincter
      achalasia (IESA) and 3 with diffuse esophageal spasm. Among NCH, 2 (13%) had IESA
      (p > 0.05). 4) Bernstein test--a positive test was seen in 5 (15%) CH and 3 (20%)
      NCH-p > 0.05. CH with esophageal dilation had 14% of positive results, while CH
      without esophageal dilation had 16%-p > 0.05. 5) Intravenous edrophonium
      esophageal contraction amplitude enhancement provoked by the drug infusion was
      clearly attenuated in the chagasic (6.9 +/- 12.7 mmHg) when compared with the NCH
      group (18.8 +/- 21.4 mmHg). A positive test (i.e. chest pain) was obtained in
      only one patient who was NCH. CONCLUSION: Esophageal pain could be elicited at a
      relatively low and comparable rate in both groups of patients.

PMID- 7575154
TI  - [Percutaneous balloon mitral valvoplasty. Immediate results, complications and
      hospital outcome].
AB  - PURPOSE: To study the short-term results, complications and in-hospital follow-up
      of 223 percutaneous mitral balloon valvuloplasty (PMBV) procedures (proc)in 219
      patients. METHODS: It was used a single 20mm balloon diameter in 4 proc, double
      balloon in 7, Inoue balloon in 4 and low profile balloon in 196. The mean-age
      group was 37.19 years. One hundred eighty three (82.1%) procedures were performed
      in women (mean age, 36.99 years) and 40 (17.9%) in men (mean age, 38.10 years) (p
      = 0.63). Patients were in functional class II, (NYHA) in 25 (11.2%) procedures,
      class III in 165 (74.0%) and class IV in 33 (14.8%). Patients were in sinus
      rhythm in 182 procedures (81.6%) and in atrial fibrillation in 41 (18.4%). The
      echocardiographic score range from 4 to 14 (7.4% +/- 1.7). Among 4 and 11 were
      98.2% of patients. RESULTS: We had 203 complete proc and success, mitral valve
      area (MVA) > or = 1.5cm2 after PMBV in 194 proc. Echocardiographic MVA before
      PMBV was 0.9 +/- 0.2cm2 and after 1.8 +/- 0.3cm2 (p < 0.01). Hemodynamic measures
      MVA before PMBV was 0.9 +/- 0.2cm2 and after was 1.9 +/- 0.3cm2 (p < 0.01). Mean
      pulmonary artery pressure decreased from 39 +/- 14mmHg to 27 +/- 11mmHg (p <
      0.01) and mitral mean gradient from 20 +/- 9mmHg to 6 +/- 5mmHg (p < 0.01). In
      the 203 proc, mitral valve (MV) was competent in 176 and there were 1+ mitral
      regurgitation (MR) in 27. After PMBV, MV was competent in 126, and there were 1+
      MR in 60, 2+ in 10.3+ in 6 and 4+ MR in 1. There was complication in 15 proc,
      severe MR in 7 (3 or 4+), stroke in 3 and cardiac tamponade in 5. Two patients
      died during emergency cardiac surgery after left ventricular perforation and one
      by stroke. CONCLUSION: PMBV was an effective procedure with a high grade of
      success and low rate of complication.

PMID- 7575155
TI  - [Treatment of renovascular hypertension in the state of Parana].
AB  - PURPOSE: To verify the incidence of treatment of renovascular hypertension (RVH)
      in the state of Parana, in a two-year period (1991-92). METHODS: Questionnaires
      were mailed to the 72 vascular surgeons members of the Brazilian Society of
      Angiology and Vascular Surgery--Parana Chapter, and to the vascular radiologists
      with experience in renal artery angioplasty. The questionnaire inquired about
      cases of RVH treated by surgery or renal artery angioplasty. RESULTS: All 8
      vascular radiologists and 38 (52.7%) vascular surgeons returned the
      questionnaires. Only 18 patients with HRV were treated in Parana: 10 by surgical
      methods and 8 by renal angioplasty. The annual incidence of treatment of RVH in
      Parana was estimated to be 0.16 cases per 100,000 adults. CONCLUSION: The
      incidence of treatment of RVH in Parana is extremely low, due to several factors:
      unavailability of diagnostic methods, absence of screening programs, and little
      information in the medical community.

PMID- 7575156
TI  - [Prevalence of residual shunt after closure of patent ductus arteriosus with
      Rashkind umbrellas].
AB  - PURPOSE: To determine the prevalence of residual left-to-right shunt in patients
      submitted to closure of patent ductus arteriosus with use of Rashkind double-disc
      ductal occluding device, analyzing predictive factors that determine short and
      long-term prevalence of residual shunt. METHODS: Thirteen patients were submitted
      to percutaneous closure of patent ductus arteriosus with use of Rashkind double
      disc device. Ten patients were male with mean age of 5.7 years. A 12mm diameter
      device was used in 7 cases and a 17mm device in the remaining six patients. All
      patients had clinical, radiological and echocardiographic follow up, after 24h, 1
      month, 6 months and one year after the procedure. Morphology and length of the
      ductus arteriosus and the presence of residual shunt after 15 min, 24h and one
      year after the procedure, were correlated. RESULTS: In one case, embolization of
      the device to the pulmonary artery determined the in success of the procedure.
      Residual shunt was present in 75% of the patients after 15 min of the procedure,
      in 33.3% after 24h, in 25% after 1 month and 6 months and in 16.6% after 1 year.
      The most important and isolated predictive factor leading to a high prevalence of
      residual shunt after 24h and after 1 year of the procedure was the presence of
      ductus arteriosus diameter > or = 4.5mm at the site of its insertion in the
      pulmonary artery. CONCLUSION: Prevalence of residual left-to-right shunt
      decreases over the time, with a low incidence after one year follow-up. A higher
      incidence of residual shunt at 24h and 1 year after the procedure occurred in the
      cases where the diameter of the ductus arteriosus was > or = 4.5mm, at the site
      of its insertion in the pulmonary artery.

PMID- 7575157
TI  - [Arterial hypertension in obese patients with heart hypertrophy. Effects of
      captopril on insulin sensitivity and growth hormone].
AB  - PURPOSE: To evaluate the effects of captopril (Cpt).on carbohydrate metabolism
      and growth hormone (GH) in adults hypertensive obese patients with normal (NGT)
      or impaired (IGT) glucose tolerance and left ventricular hypertrophy. METHODS:
      Ten patients (53 +/- 8 years), 8 women and 2 men, white, body mass index (BMI) >
      or = 26kg/m2, left ventricular mass index (LVMI) > 135g/m2 in man and > 110g/m2
      in woman, with diastolic blood pressure (DBP) 95-115mmHg after 3 weeks of
      placebo, were identified by oral glucose tolerance test (OGTT-75g) as either with
      NGT or IGT, and treated with Cpt 25mg t.i.d. for 8 weeks. At the 8 weeks, dosage
      was increased to 50mg b.i.d. if DBP > 90mmHg or the decrease of the DBP < 10%,
      during the next 8 weeks. OGTT and clonidine tests (0,04mg/kg) with
      determinations, every 30 minutes of glucose, insulin, and GH during 2 hours, were
      performed. RESULTS: Cpt lowered SBP and DBP in the NGT group and IGT group. The
      LVMI and the left ventricular mass (LVM) decreased in the IGT group with no
      significant change in the NGT group. Cpt promoted in the IGT group decrease in
      the area under the curve (AUC) of glucose, and AUC of insulin, with increase of
      the AUC of the percent of the beta cell function, AUC of HC, and insulin
      sensitivity index with no significantly change in the NGT group. CONCLUSION:
      Adults hypertensive obese patients with IGT had decreased significantly in mean
      fasting level of GH concentrations compared to age, race, and BMI matched
      hypertensive patients with NGT. Treatment with Cpt induced a significant
      increased of the GH, with improvement of the metabolism in patients with IGT.

PMID- 7575158
TI  - [Agenesis of the right pulmonary artery with severe pulmonary hypertension,
      attenuated by surgical correction].
AB  - A 22 months old infant with agenesis of right pulmonary artery, without other
      associated congenital heart defects, is reported. Reconstruction of pulmonary
      arteries by connecting them through a 7mm Goretex tube was performed, with clear
      clinical improvement in view of disappearance of signs of cardiac insufficiency
      and of hypoxemia. Contralateral pulmonary hypertension, at systemic level,
      decreased to 77% in the immediate postoperative period. So, this technique
      becomes the first option, before considering these cases for cardiopulmonary
      transplantation.

PMID- 7575159
TI  - [Correlation between hyperinsulinemia and essential hypertension. Current
      situation].

PMID- 7575160
TI  - [Hypertension in woman. A special case?].

PMID- 7575161
TI  - [To normalize the lipidogram. Why, how, and how much?].

PMID- 7575162
TI  - [Indications for electrophysiological studies and catheter ablation of cardiac
      arrhythmias. Recommendations of the Department of Arrhythmias and Clinical
      Electrophysiology of the Brazilian Society of Cardiology].

PMID- 7575164
TI  - [Reactivation of Chagas carditis inducing exclusive right ventricular failure].

PMID- 7575163
TI  - [Esophageal etiology of precordial pain in chagasic patients].

PMID- 7575165
TI  - [The athlete heart. Physiological modifications x overtraining and heart
      disease].

PMID- 7575167
TI  - [Metabolic and ventilatory thresholds during exercise. Physiological and
      methodological aspects].

PMID- 7575166
TI  - [Physical practicing of athletes. Methodology and training].

PMID- 7575168
TI  - [Cardiorespiratory evaluation of athletes for competitions at high altitudes].

PMID- 7575169
TI  - [Atrial fibrillation and Wolff-Parkinson-White syndrome. The hidden danger of
      manifested pathways].

PMID- 7575170
TI  - [Treatment of ascites: looking for the good and the inexpensive].

PMID- 7575171
TI  - [Paracentesis associated to dextran-70 in the treatment of ascites in patients
      with chronic liver diseases: a randomized therapeutic study].
AB  - The treatment of ascites of large volume in chronic liver disease patients was
      evaluated in the present study. We compared diuretics with paracentesis and an
      infusion of Dextran-70. Therapeutic efficacy, complications and length of
      hospital stay were the variables studied. Of the 38 patients, 20 were selected
      randomly. They were evaluated using clinical, laboratory and/or histological
      criteria: 10 patients in the paracentesis group with Dextran-70 and 10 in the
      diuretic group. The groups were similar with respect to age, diagnosis and Child
      Pugh classification. However, there was a greater number of males in the
      paracentesis group with Dextran-70. In each paracentesis, an average of 9.41
      liters (4.5 to 14.1) of ascitic fluid was collected. The average hospitalization
      period in the paracentesis group with Dextran-70 was 10.5 days (8-14),
      significantly less when compared to the diuretic group: 24.4 days (14-48). In the
      diuretic group one patient presented complications such as hyperkalemia,
      increased urea and creatinine levels, while in the paracentesis group with
      Dextran-70 one patient presented a temperature above 38 degrees C during
      treatment. The results suggest that paracentesis associated with Dextran-70 could
      be a therapeutic alternative for chronic liver disease patients with ascites in
      our population. It was effective; it had no significant side effects; it reduced
      the length of hospital stay and therefore should decrease the cost and the risk
      of complications in patients requiring prolonged hospitalization periods.

PMID- 7575172
TI  - [Trends of peptic ulcer mortality in Sao Paulo State (Brazil), 1970-1989].
AB  - BACKGROUND: Trends of peptic ulcer mortality rates were studied in Sao Paulo
      State (Brazil) among 1970 and 1989. MATERIAL: Deaths from PU, ICD-9 531-534.
      RESULTS: The PU rates in Sao Paulo are comparable with those in Europe and rank
      second place for males and in third place for females. During this period there
      was a downward trend either for males or females. CONCLUSIONS: For women, the
      decline was less impressive and the male/female ratio decreased. A cohort effect
      was suspected for the explanation of female mortality trends.

PMID- 7575173
TI  - Electromanometry of the rectosigmoid in colonic diverticulosis.
AB  - In order to better understand the rectosigmoid motor activity in diverticular
      disease of the colon, we studied 186 patients, grouped according to their
      intestinal habit, the presence of diverticular disease and previous crisis of
      sigmoid diverticulitis. The intestinal habit was classified as: normal habit,
      irritable colon syndrome, diarrhea and constipation. The group of diverticulosis
      was classified by their intestinal habit and by diverticula localization
      (localized or generalized). The presence of systemic diseases or drug ingestion
      that could modify intestinal motility, were considered criteria for exclusion.
      The manometric study was preceded by food stimulus, with 650 kcal meal, by
      mechanic intestinal cleansing, with 500 ml of saline solution enema and by one
      hour resting period. A manometric catheter, was introduced by rectosigmoidoscopy,
      with open ended orifices situated at the sigmoid and upper rectum, respectively.
      The catheter was perfused by a capillary infusion system and the bowel pressures
      were registered for 30 minutes, in a thermal paper physiograph. We analyzed the %
      of activity, mean amplitude and motility index, by non parametric tests. No
      significant difference was observed between sexes. Difference or close to it were
      found for the groups with constipation, with or without diverticulosis, and for
      the latter in its subdivisions (localized, generalized and sigmoid
      diverticulitis). The rectal motor activity was similar in all groups. There was
      no difference for diverticulosis and its subdivision, when we take into account
      the several kinds of intestinal habits and the diverticula localization. The
      motility index averages showed low values for the sigmoid diverticulitis fact
      that suggests some dysfunction of this segment (hypocontractility). The key
      factor differentiating the groups was the presence of constipation and no
      influence was noted regarding the localization of diverticula or previous
      inflammatory process on intraluminal pressures. The fact that no difference was
      found in the mean amplitude or % of activity among patients with or without
      diverticulosis, suggests that the high pressures in a colonic segment, may not be
      responsible for the diverticular disease, and there must be other factors,
      besides motility, accounting for the development of the different forms of this
      disease.

PMID- 7575174
TI  - [Peutz-Jeghers syndrome and adenocarcinoma. Report of a case].
AB  - Peutz-Jeghers syndrome is a rare disease, characterized by autosomic inheritance,
      presenting skin stain and hamartomatous polyps. We report one case of Peutz
      Jeghers syndrome and duodenal adenocarcinoma in a young male who presented with
      liver metastasis and pancreatic invasion. Such association is reported to be
      presented in 5% of patients with the syndrome. The reasons of such association
      are unknown, being possible that: 1) there is malignant degeneration of a
      adenomatous polyp; 2) malignant degeneration of a hamartomatous polyp, or 3)
      adenomatous portion of a hamartomatous polyp could undergo malignant
      transformation.

PMID- 7575175
TI  - [Splenic artery aneurysm in patients with hepato-splenic schistosomiasis mansoni
      and portal hypertension. Report of 3 cases].
AB  - The authors present three cases of splenic artery aneurysm in a group of 96
      patients with portal hypertension due to Schistosomiasis mansoni. Etiology,
      diagnosis and treatment are discussed.

PMID- 7575176
TI  - [Serum antigliadin antibodies in the diagnosis and follow-up of celiac disease].
AB  - Between July 1985 and June 1990, we prospectively investigated 236 children
      suspected of having malabsorption syndrome. Each patient had a xylose absorption
      test and small intestinal biopsy. Blood samples were collected to AGA assay. The
      aim of the study was to evaluate the use of antigliadin antibodies test, IgG and
      IgA, in screening celiac disease for intestinal biopsy and in the monitoring of
      gluten-free diet and challenge in celiac patients. Twenty patients were diagnosed
      with celiac disease confirmed by three small intestinal biopsies; 12 patients
      were suspected of having celiac disease, with two biopsies, before and one year
      after a gluten-free diet; 106 patients had environmental enteropathy; 45 patients
      had protracted diarrhea and 56 children had failure to thrive with no
      gastrointestinal symptoms. The AGA test was considered a reliable test in
      screening for biopsy and in the differential diagnosis between celiac disease and
      other causes of malabsorption syndrome. The IgG AGA test had high sensitivity
      (90.4%) and the IgA AGA test had high specificity (92.1%) in screening for celiac
      disease. In the follow-up of the celiac patients the antibody levels were
      significantly higher during gluten containing diet than after gluten avoidance
      being thus a reliable test to evaluate dietary compliance.

PMID- 7575178
TI  - [Presbyesophagus--the maturity of a concept].

PMID- 7575177
TI  - [Growth hormone secretion and nutrition].
AB  - Growth hormone has direct and indirect actions through which it stimulates growth
      of skeletal and other tissues and influences the availability of metabolic fuels.
      The growth promoting actions of growth hormone are indirect and mediated through
      generations of insulin-like growth factors. The direct actions of growth hormone
      are predominantly antagonist to insulin, although there are acute insulin-like
      effect of physiological significance. Growth hormone release is determined by a
      dynamic equilibrium between the inhibitory and stimulatory hypothalamic peptides,
      somatostatin and growth hormone-releasing hormone. The hypothalamic-pituitary
      response may be influenced by age, sex, insulin, thyroid and steroid hormone, and
      nutritional status. There is an important interrelationship between the action of
      growth hormone, nutrition and growth.

PMID- 7575179
TI  - [Small hepatocellular carcinoma. New concepts on intrahepatic recurrence after
      hepatectomy in orthotopic liver transplantation].
AB  - Hepatocellular carcinoma is one of the most common cancers worldwide.
      Epidemiologic studies shows a striking correlation between areas where this tumor
      is prevalent and where hepatitis virus B and C are endemic, contaminations of
      food with mycotoxin aflatoxin B1, excessive alcohol intake, prolonged cigarette
      smoking, sexual hormones. Combination of chemical, physical, and genetic insults
      to individual hepatocytes involve changes in the genome transformed or neoplastic
      cell, depending to both the activation of oncogenes (e.g., ras) and the
      inactivation of tumor supressor genes (e.g., p53). Advances in radiologic
      techniques such as ultrasonography, computed tomography, angiography and dosages
      of tumor markers like alpha-fetoprotein offers still the best for diagnosis and
      screening for hepatocellular carcinoma. Then the diagnosis has become possible
      during the early stages, characterized to be a very well-differentiated tumour
      that has returned its preexisting liver structure, with a certain proportion have
      a multicentric origin. Hepatocellular carcinoma carries an extremely poor
      prognosis, with a median survival between 2-4 weeks, for those without treatment.
      Surgical resection are the only curative modality for this disease. In these
      patients two main patterns of intrahepatic recurrence after hepatectomy are
      defined, and depends on the growth of residual satellite tumours or synchronous
      and metachronous multicentric carcinogenesis. This evolution is estimated to be
      nearly 50%, with 5-year survival rate of nearly 30%. The presence of cirrhosis,
      satellite nodules, venous invasion, the absence of capsule formation and positive
      surgical margin (< or = 5 mm) were associated with higher intrahepatic recurrence
      rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575180
TI  - [Small intestine flora in chagasic patients with megaesophagus and/or megacolon:
      study using the H2 breath test].
AB  - The author use the H2 breath test to study the small bowel microflora of chagasic
      patients with megaesophagus and/or megacolon. Compare this group with a control
      one. Find a significant increase (P < 0.05) in the small bowel flora of chagasic
      group. It is concluded that H2 breath is a simple and useful test to detect
      alteration in intestinal flora.

PMID- 7575182
TI  - [Esophageal motility in the patient over 70 years old].
AB  - The aging process causes a progressive loss of the intrinsic esophageal
      innervation that may impair esophageal motility. Esophageal motility was studied
      by the manometric method in 30 symptomatic patients aged 70 to 83 years (median
      72 years). The most frequent symptom was dysphagia, followed by chest pain.
      Eleven patients had Chagas' disease, with esophageal motility similar to that
      found in patients with the disease and of all ages. Thirteen patients had
      systemic diseases or esophagitis. Simultaneous contractions of low amplitude were
      found in five, normal motility in seven, and peristaltic contraction of low
      amplitude in one. The other six patients did not have systemic diseases or
      esophagitis. Esophageal motility was normal in two, the contractions were
      simultaneous in four, of low amplitude in three, and of high amplitude in one.
      These patients were interpreted to have presbiesophagus.

PMID- 7575181
TI  - [Comparative study of the suture of pancreatic stump with absorbable and
      unabsorbable threads in rats].
AB  - The safety of suture and healing of pancreas after surgery with absorbable and
      unabsorbable suture was studied. One hundred and twenty female rats was underwent
      a segmentar pancreatic resection. The pancreatic suture was performed with catgut
      in Group I (n = 48), polygalactin in Group II (n = 48) and silk in Group III (n =
      24). The animals were sacrificed at 5th, 10th, 20th and 30th days after surgery
      and analized at macroscopy: inflammatory signs, fistula, abscess and suture
      bearing in tissue. Microscopic findings were: suture bearing in tissue,
      inflammatory aspects against suture, necrosis, edema, neovascular modifications,
      fibrosis and the collagen's type. After comparing the results with Wilcoxon's two
      sample test, we concluded that pancreatic healing was not modified with
      differents sutures, and then pancreatic absorbable or unabsorbable suture was
      safe.

PMID- 7575183
TI  - [Endoscopic treatment of colon vascular ectasia during bleeding with injection of
      adrenaline solution at 1:10,000 and monopolar electrocoagulation: an alternative
      approach. Case report].
AB  - Gastrointestinal bleeding accounts for 2% of all adult hospital admissions each
      year. Vascular ectasia is one of the most frequently reported cause of lower
      gastrointestinal bleeding. In almost 80% of patients with bleeding vascular
      ectasia will stop spontaneously, but will often recur. Many treatments are
      proposed like superselective catheterization with infusion of vasoconstrictor by
      angiography, Laser photocoagulation, heater probe, bipolar electrocoagulation,
      hot biopsy forceps, have been used in colonoscopy, but some effects are short
      lived others are so expensive and without an effective treatment. The authors
      present one case of bleeding vascular ectasia during colonoscopy submitted to a
      new, cheap and effective approach with injection a 1:10,000 solution of
      epinephrine following electrocoagulation by colonoscopy.

PMID- 7575184
TI  - Nutrition-physiology link. Need to increase basic research.
AB  - Some complex mechanisms of intestinal absorption are commented in relation to
      their link with interactions among nutrients, or to the alimentary system itself.
      The nutrient bioavailability is also considered in relation to the individual
      nutritional status in order to emphasize the need of depth knowledge in
      physiology for the best understanding of nutrition and reciprocally.

PMID- 7575185
TI  - [Lactose content and beta-galactosidase activity in yogurt, cheeses and curdled
      milk made in Brazil].
AB  - We studied yogurts and industrialized curdled milk in three different storage
      times, as well as homemade and Syrian curdled milk and cheeses. Lactose content
      (gm%) and beta-galactosidase activity were determined in these products. Lactose
      content was elevated in yogurts and curdled milk with a lactose reduction of
      about 22% compared to the lactose of cow milk, with a mean and standard
      desviation (M +/- SD) of 3.81 +/- 0.47 gm%. In the cheeses lactose content was
      low, between 1.91 and 0.03 g%. beta-galactosidase activity was present in yogurts
      and curdled milk, with values between 0.58 and 3.61 U in time I and M +/- SD of
      0.15 +/- 0.23 U. A significant decrease of beta-galactasidase activity was
      observed during the storage time. By analyzing and comparing these findings with
      the literature, we conclude that the products studied, by their low content of
      lactose (cheeses and yakult) or by the presence of beta-galactasidase activity
      (yogurts and curdled milk at time I) probably would be tolerated by most
      hipolactasic persons.

PMID- 7575186
TI  - Professional liability of midwives in employment and private practice.

PMID- 7575187
TI  - Australian College of Midwives Inc. Position statements.

PMID- 7575189
TI  - Midwifery in Sweden.

PMID- 7575188
TI  - Routine ultrasound scanning in pregnancy.

PMID- 7575190
TI  - Ventilator circuitry in neonatal intensive care: extending the period between
      changes from 4 to 7 days. A pilot study.
AB  - OBJECTIVE: To determine the effect of increasing the time span between changes of
      disposable ventilator tubing from 4 to 7 days. DESIGN: A prospective non
      randomised study comparing levels of bacterial colonisation amongst babies who
      had ventilator circuits changed on either the 4th or 7th day. Data was collected
      sequentially with data collection from the '4-day group' preceding data
      collection from the '7-day group'. SETTING: A tertiary neonatal intensive care
      nursery. PATIENTS: All babies requiring ventilation at the time when data
      collection was possible. Ten babies were included in the first group (4 days) and
      33 babies in the second group. INTERVENTIONS: Inspiratory and expiratory lines
      were swabbed and water from the humidifier trap sampled before the line was
      changed at either 4 or 7 days. Results of routine endotracheal aspirates, taken
      before and after the change of circuitry, were noted. MAIN OUTCOME MEASURE: The
      level of bacterial contamination of ventilator circuits. RESULTS AND CONCLUSIONS:
      In this small sample, no differences were found in terms of bacterial
      colonisation of ventilator lines. This has resulted in a change of practice in
      the hospital and a cost saving of over $15,000.

PMID- 7575191
TI  - Professional indemnity and other medico-legal matters: a midwifery concern?

PMID- 7575192
TI  - [Treatment of Parkinson disease].
AB  - Parkinson's disease (PD) accounts for 58% of patients with Parkinsonism. The
      second most common cause is drug-induced Parkinsonism, diagnosed in 20% of
      patients. Levodopa remains as the mainstay of PD treatment. Although there is
      controversy regarding the timing for beginning levodopa, it should be used when
      the patient develops significant disability. Other drugs that may be used are
      anticholinergic agents, useful for tremor; amantadine, for rigidity and
      bradykinesia; dopamine agonists, for the management of levodopa complications;
      and selegiline which may be a neuroprotector agent. Problems in the management of
      PD include primary failure, secondary failure and levodopa complications.
      Antidopaminergic drugs, severe rest tremor and diagnosis error may lead to
      primary failure. Progression of PD is the most common explanation for secondary
      failure. The most important levodopa therapy complications are dyskinesias and
      fluctuations. Other common problems are dysautonomia, depression, psychosis and
      dementia. The author discusses the phenomenology and management of these
      complications. Future perspectives include brain repair surgeries.

PMID- 7575193
TI  - [Cognitive disorders in Parkinson disease. Electroencephalographic correlations].
AB  - Sixty-two patients with idiopathic Parkinson disease and 30 patients of a control
      group were clinically evaluated in the light of cognitive and/or psychic
      impairments according to DSM III-R, mini-mental state examination and Hamilton
      rating scale for depression. These patients were also submitted to
      electroencephalogram registration (EEG) with photic stimulation. From the
      parkinsonian group, 45.2% did not have mental manifestations as classified in the
      DSM III-R. Other 24.2% had depression, 14.5% had anxiety, 12.9% had dysthymic
      disorder and 3.2% had dementia. Considering the EEG, 58.1% of the parkinsonian
      patients had theta waves bilaterally, with predominance in frontal temporal or
      temporal areas, though more frequent on the left hemisphere than on the right
      one. Only 16.7% of the patients from the control group had these same findings in
      the EEG but neither of the two groups had their EEG modified by photic
      stimulation. The EEG findings were statistically significant when both groups
      were compared. However, these findings were not significant comparing
      parkinsonian patients with psychic impairment with the ones who did not have such
      impairments.

PMID- 7575194
TI  - Autosomal recessive nondystrophic myotonia. Report of a case with unusual
      clinical course.
AB  - We describe the case of a girl with a probable autosomal recessive form of
      nondystrophic hereditary myotonia whose clinical findings are more compatible
      with the dominant ones mainly myotonia congenita of Thomsen or myotonia
      fluctuans. Besides the clinical aspects of the atypical form presented by our
      patient, the efficacy of the more available drugs employed for the treatment of
      myotonia congenita is briefly discussed.

PMID- 7575195
TI  - [Hemichorea associated with cerebral toxoplasmosis and AIDS].
AB  - Only 12 AIDS cases with hemichorea were reported in the literature. We report the
      first case of hemichorea associated with AIDS and cerebral toxoplasmosis in our
      country. A 26-year-old man had 3 episodes of focal seizures on the left side with
      subsequent loss of consciousness. A few weeks later, he noticed progressive left
      sided weakness. Examination revealed a left hemiparesis. MRI of the head showed a
      round mass in the right frontal lobe and a smaller lesion in the left temporo
      occipital area. Laboratory showed positive serum ELISA and Western Blot analysis
      for HIV antibodies. Serum tests for Toxoplasma showed elevated titers. He was
      treated with pyrimethamine and sulfadiazine. His weakness improved and he had no
      further seizures. Two weeks later, choreic movements appeared in the left foot,
      finally involving the entire left hemibody. A second MRI showed a new small
      lesion in the right cerebral peduncle. The patient completed 6 weeks of
      treatment, with further reduction in the size of the lesions. Nevertheless, the
      left hemichorea persisted. We believe that the hemichorea our patient had was
      caused by the contralateral peduncular lesion. Lesions involving the subthalamic
      nucleus or its connections may cause contralateral hemiballismus or hemichorea.
      In spite of the favorable response to antitoxoplasmic therapy, the hemichorea
      persisted. The present report illustrates an uncommon neurological complication
      in AIDS. We believe that a combination of a focal cerebral lesion and the HIV
      infection caused the movement disorder presented by the patient.

PMID- 7575196
TI  - Lymphomatous meningoencephalitis in a patient with HAM/TSP.
AB  - A case of lymphomatous meningoencephalitis in a 23 year old Brazilian patient
      with HTLV-I/II associated myelopathy is reported. The patient was admitted to the
      hospital with a clinical picture of decreased consciousness level, stiffness of
      the neck and previous diagnosis of myeloneuropathy. CSF examination showed
      lymphocytosis with blastic cells and antibodies against HTLV-I/II.

PMID- 7575197
TI  - [Spinal subdural empyema. A case report].
AB  - Spinal subdural empyema is a very unusual condition. About 40 cases have been
      previously reported. The authors describe another case, mentioning the
      difficulties in diagnosis particularly when no primary infection is known. In
      these circumstances, the neurological signs and MRI are important; MRI
      demonstrates the level of the lesion and its subdural localization. Surgical
      treatment and antibiotics are clearly indicated and the earliest it is done, the
      better the results.

PMID- 7575198
TI  - [Relevance of ventilatory optimization in acute intracranial hypertension. A
      clinical, physiological, and therapeutic approach].
AB  - Mechanical ventilation in acute traumatic coma is comprehensively approached, by
      means of comparatively reviewing the pertinent literature. Multivariate clinico
      physiologic-therapeutic aspects are presented and discussed, and a proposition is
      made for ventilatory optimization under circumstances of predominantly diffuse
      acute brain insults. A novel technique is introduced for practical, bedside
      quantification of ventilatory adjustments. This technique allows simultaneous
      optimization of intracranial pressure and global cerebral extraction of oxygen.
      The latter represents therapeutic coupling between global cerebral blood flow and
      oxygen metabolism.

PMID- 7575199
TI  - [Tics and Gilles de la Tourette syndrome].
AB  - The concept of tic was developed at the end of the XIX century, emerging from the
      "chaos of choreas". Tic is defined as involuntary contractions of agonist and
      antagonist muscles in one or more parts of the body. It can be suppressed by
      voluntary efforts for seconds or hours, followed by exacerbations. Gilles de la
      Tourette's original article was published in 1885, in which he described nine
      patients with tics, and vocalisations. The pathogenesis of Gilles de la Tourette
      syndrome remained obscure. However, three factors have been considered: the
      neurochemical factor, related to the increased dopaminergic activity at the basal
      ganglia; the genetic factor and the non-genetic factors, for which environment
      more than genetic factors are involved. Pathologic examinations failed to reveal
      structural lesions, but PET studies showed metabolic hypofunction on the frontal,
      cingulate and possibly insular cortex, and on the inferior corpus striatum. The
      motor tics as well as the vocal tics can be simple or complex and are present in
      all patients. Other signs can be added to the previous tics: sensory tics,
      echophilia, coprophilia, obsessions, compulsions and impulsions. Diagnostic
      criteria of Gilles de la Tourette syndrome are based on: age of onset; presence
      of motor and vocal tics; voluntary suppression of the movements; variation in
      number, type, location and severity of tics; duration of more than one year.
      Haloperidol is the drug of choice for the treatment of Tourette's syndrome.

PMID- 7575200
TI  - [Adequate neuropsychological evaluation of dementia].
AB  - The authors discuss the protocol of the Optimal Neuropsychological Evaluation of
      Dementias of Montreal and its possible application in Brazil. This protocol is
      important for evaluation in neuropsychological evolution of dementia of the
      Alzheimer type and for bringing to the fore distinct affected cognitive profiles
      as much on a transversal base as longitudinal. The authors believe that its
      application would contribute to the progress of research in neurology, as in the
      clear distinction between normal aging and pathological aging.

PMID- 7575201
TI  - The use of humor in psychotherapy.
AB  - Humor can be a useful treatment technique in the hands of some psychotherapists.
      It may help the patient to see painful life events and situations from less
      threatening perspectives, and can take the anxiety and guilt out of many
      difficult circumstances and incidents. Humor can be valuable in talking with
      parents about the problems of their adolescent children, in working with
      adolescents themselves, in discussing difficulties encountered in the workplace
      and in social environments, in decreasing obstructive awe of the therapist and
      apprehensiveness about treatment, in dealing with problems such as male sexual
      impotence, and in many other areas. Some therapists, however, handle humor
      awkwardly; in their hands it misfires or falls flat, and they should avoid it.

PMID- 7575202
TI  - [The importance of clinical hemorheology in the study of cerebral blood flow in
      normal conditions and in cerebrovascular ischemia].
AB  - A critical review on the importance of hemorheology for establishing clinical
      management of acute cerebrovascular insufficiency is presented. With this purpose
      a revision is made on cerebral blood flow, acute cerebrovascular insufficiency,
      and clinical hemorheology. Data support an evaluation on main drugs presently
      used in the management of stroke, and on general principles adopted for medical
      treatment and prevention of stroke.

PMID- 7575203
TI  - [Psychosocial evaluation in epilepsy: experience with a version of WPSI].
AB  - Epilepsy has frequently been associated with important psycho-social problems.
      Washington Psychosocial Seizure Inventory is a inventory developed to identify
      the psycho-social problems in epilepsy. In this study we applied a WPSI version
      for a psychosocial evaluation of Brazilian patients: 54 epileptic patients
      answered a questionnaire in a period of 7 months. The application of WPSI showed
      difficulties in the scales: adjustment to seizures, financial status, vocational
      adjustment, emotional and interpersonal adjustment. The scores of problems were
      lower in the scales of family background, medicine and medical management. Level
      of schoolarity, employment status, seizure type, duration of epilepsy, control of
      seizures were factors influencing WPSI results. Difficulties were noticed in the
      comprehension of some words by the illiterate patients, and in high scores for
      validity scales. Our initial results were comparable to the literature. However,
      it should be necessary an adaptation of some language aspects and validity
      scales, and a further application in a larger number of epileptic patients to
      validate our WPSI version.

PMID- 7575204
TI  - [Refractory epilepsy in childhood].
AB  - The study of epileptic syndromes in children displaying a poor prognosis reveals
      common characteristics which allow the delineation of a clinical profile. In this
      study, hospital records of a treatment of convulsions in children were analysed
      during a two year period. We observed that the majority of cases presented this
      clinical profile.

PMID- 7575205
TI  - Changes of blood flow velocity indicating mechanical compression of the vertebral
      arteries during rotation of the head in the normal human measured with
      transcranial Doppler sonography.
AB  - The dynamical changes of blood flow velocity of the intracranial vertebral
      arteries (VA's) and proximal basilar artery (BA) provoked by rotation of the head
      in normal volunteers were measured using pulsed-wave transcranial Doppler
      sonography (TCD). In another group both VA's were examined simultaneously with 2
      channel TCD. Blood flow velocities diminished compared to the neutral position in
      all vessels, independently of the side. Total obstruction of the flow was not
      observed. Our findings reveal a definitive decrease of blood flow velocity at the
      vertebrobasilar artery system provoked by rotation of the head in normal humans.
      This physiological phenomenon is suggested to have an impact on the cerebral
      blood flow in patients with impaired autoregulation of the cerebral vessels, low
      volume flow reserve in the contralateral VA or insufficient collateral channels
      because of normal anatomical variation, especially those patients under general
      anesthesia or comatose.

PMID- 7575206
TI  - Surgical considerations about the anterior syphon knee of the internal carotid
      artery. An anatomical study.
AB  - An anatomical study about the anterior knee of the intracavernous carotid artery
      is presented. Twenty cavernous sinuses (CS) were dissected in cadavers using
      microsurgical techniques. A fibrous ring around the internal carotid artery (ICA)
      at the CS roof was found in all specimens. This fibrous attachment could be
      dissected from the surrounding dura and a loose connective tissue could be
      demonstrated around the ICA. This anatomical finding makes possible the
      microsurgical approach to vascular lesions of this portion of the ICA, without
      opening the cavernous sinus.

PMID- 7575207
TI  - [Linear accelerator radiosurgery].
AB  - Radiosurgery is the precise radiation of a known intracranial target with a high
      dose of energy, sparing the adjacent nervous tissue. Technological advances in
      the construction of linear accelerators, stereotactic instruments and in computer
      sciences made this technique easier to perform and affordable. The main
      indications for radiosurgery are inoperable cerebral vascular malformations,
      vestibular and other cranial schwannomas, skull base meningiomas, deep seated
      gliomas and cerebral metastases. More recently, the development of fraccionated
      stereotactic radiotherapy increased the spectrum of indications to bigger lesions
      and to those adjacent to critical nervous structures. We present our initial
      experience in the treatment of 31 patients. An adequate control of the neoplastic
      lesions was obtained and the adequate time of observation is still needed to
      evaluate the results in arteriovenous malformations.

PMID- 7575210
TI  - [Correlation between functional disability, age, and serum enzymes in
      neuromuscular diseases].
AB  - We attempt to correlate the patient's disability and serum enzymes
      (creatinekinase, lactic dehydrogenase, aldolase, glutamic oxalacetic and glutamic
      piruvic transaminase) in several neuromuscular disorders using the Vignos and
      Archibald scale (V&A). In 806 cases we studied, serum enzyme levels and the V&A
      disability using a computer for Pearson's correlation and regressive analysis. A
      good correlation of the V&A with age suggested a progressive evolution (increased
      disability) in Duchenne muscular dystrophy, fascioscapulohumeral dystrophy,
      myotonic dystrophy, myopathies due to respiratory chain enzyme deficiency and
      amyotrophic lateral sclerosis. A negative correlation (decrease disability with
      age) was found for multicore myopathy, benign myopathy of childhood with type 1
      predominance, carnitine myopathy deficiency and dermatomyositis. It was found a
      correlation (p < 0.05) of the V&A and the level of specific serum enzymes with
      Duchenne muscular dystrophy, oculocraniosomatic dystrophies, polymyositis and
      polyarteritis nodosa. Using regression analysis, we found a weak interrelation
      between serum enzymes studied simultaneously and the V&A. These weak relations
      suggest some limitation in the long term use of the five serum enzymes in the
      evaluation of neuromuscular disorders when compared with V&A; although they are
      very important in the diagnosis.

PMID- 7575208
TI  - Sleep-related laryngospasm.
AB  - Seven patients (mean age 46.6; range 33-58; 6M,1F) presented with sleep-related
      choking episodes and were found to have features in common that distinguished
      them from other known causes of choking episodes during sleep. The characteristic
      features include: an awakening from sleep with an acute choking sensation,
      stridor, panic, tachycardia, short duration of episode (less than 60 seconds),
      infrequent episodes (typically less than 1 per month), and absence of any known
      etiology. The disorder most commonly occurs in middle-aged males who are
      otherwise healthy. In one patient an episode of laryngospasm was
      polysomnographically documented to occur during stage 3. The clinical features
      and the polysomnographic findings suggest spasm of the vocal cords of unknown
      etiology.

PMID- 7575209
TI  - [The knowledge of neurological changes in patients with AIDS].
AB  - We performed a retrospective study of 154 patients with AIDS that presented
      lesions of the nervous system at necroscopic examination. Necropsies were
      performed in the Hospital Universitario Antonio Pedro (Niteroi, Brazil). We
      emphasize epidemiologic and clinical data, neuropathologic findings, evolution
      time, and anatomo-clinical correlation. Data obtained can contribute in the
      definition of consequences of neurologic symptoms and signs for early diagnosis
      and best prognosis in AIDS.

PMID- 7575211
TI  - [CSF total proteins in the prognosis of patients with subarachnoid hemorrhage].
AB  - The main purpose of this study was to verify the value of CSF total proteins
      level on the prognosis of subarachnoid hemorrhage. In order of this, samples of
      254 patients with diagnosis of intracranial bleeding were analyzed, with special
      attention to the rate of CSF total proteins. Statistical tests for evaluation of
      the results have been accomplished, revealing a close relationship between the
      total proteins rates increase and death in patients with subarachnoid hemorrhage,
      independent of sex and age. The limit score of total proteins level for survive
      was 3000 mg/100 ml (nephelometric method).

PMID- 7575212
TI  - [Vascular stroke of the brain stem. Study of 21 cases].
AB  - A prospective study was designed to follow patients with syndromes of brain stem
      during 12 months (in 1991-1992). The aim was to correlate clinical and radiologic
      findings and comparing them with the classical descriptions of brain stem
      syndromes. Twenty one consecutive patients were admitted at the Hospital de Base
      do Distrito Federal. The diagnosis and the follow up were carried out by
      neurological examination and neuroradiologic images: CT (100%), angiography (24%,
      5) and MRI (5%, 1). Hypertension and old age were the most important risk factors
      and hemorrhage at pons with extension to midbrain was the most frequent finding.
      Coma at admission was associated to a poor outcome. The outcome was defined by
      the Glasgow Outcome Scale: 28% rated 5, 24% rated 4, 5% rated 3, 28% rated 2 and
      14% rated 1. Our results show that the clinical presentation of ischemic strokes
      and hemorrhages of the brain stem very frequently follow a mixed pattern, which
      do not conciliate with the classical of these syndromes.

PMID- 7575213
TI  - [Sneddon syndrome. Report of 3 cases].
AB  - The Sneddon's syndrome consists of neurologic manifestations associated to the
      presence of livedo reticularis and cyanosis of the extremities. The pathological
      process is an endothelial obliteration of arterioles, leading to a reticular
      appearance of the skin, despite the environment temperature. The authors present
      three new cases, caucasian males with 7, 16 and 54 years of age. The youngest
      started with hemilateralized motor seizures and showed a porencefalic area in the
      CT scan. The oldest had livedo reticularis, acrocyanosis and started with
      hemilateralized motor seizures, and a hemiparesis as sequela; CT scan with
      parasagittal infarct and occlusion presented of one anterior cerebral artery on
      angiography. The third patient started with hemifacial seizures, developed a
      labioglossolaringeal paresis and dysarthria as sequela; CT scan and MRI showed
      multiple infarcts, with multiple occlusions of cortical branches on angiography.
      The skin biopsies showed endothelial vascular hyperplasia in all cases. Only one
      (54 years old) patient had a positive IgG antiphospholipid antibodies. The
      Sneddon's syndrome seems not to be so rare and have to be considered in the
      etiological investigation of cerebral infarcts, mainly in young people.

PMID- 7575214
TI  - [Hemispheric functional specialization in motor aphasia. Neurophysiologic
      findings with computerized electroencephalographic brain mapping during musical
      and oral sound stimulation. Study of 2 cases].
AB  - This study concerns about brain electrical activity during auditory stimulation
      in 2 aphasic patients, one with classical (left hemisphere lesion) and another
      with cross aphasia (right hemisphere lesion). Both cases were submitted to
      dichotic listening test (consonant-vowel-consonant task) and music audition
      (gregorian chant), during brain mapping examination. We found, in both cases, a
      great proportion in delta frequency and power in non-lesional hemisphere during
      dichotic and musical stimulation. Besides, increasing in frequency of alpha
      activity was observed only in the non-lesional hemisphere restricted to temporal
      lobe region. Such findings suggest an interesting field of research about
      measurements of neurophysiological correlates of auditory stimulation and brain
      electrical activity in aphasia.

PMID- 7575215
TI  - [Mutism after posterior fossa tumor surgery. Report of 2 cases].
AB  - The authors present two cases of mutism after posterior fossa surgery. Two
      patients aged 16 and 5 years old respectively with astrocytoma and
      medulloblastoma, developed mutism after the operation. Topographic aspects of the
      condition are discussed and its neurological expression.

PMID- 7575216
TI  - [Magnetic resonance of brain involvement in progressive facial hemiatrophy
      (Romberg's disease). Reconsideration of a syndrome].
AB  - Progressive facial hemiatrophy (PFH) is a sporadic disease of unclear etiology,
      characterized by shrinking and deformation of one side of the face. Reports and
      interpretations of CNS involvement in PFH, as deduced from the occurrence of
      seizures in some patients and documented by pneumoencephalography and CT findings
      in small series of patients, are contradictory. We examined three female patients
      with PFH, one with partial epilepsy, with the view to gaining further insight
      into the pathogenesis of the disease. METHODS: Routine MR examinations of the
      head and face were performed. RESULTS: Only the patient with epilepsy showed
      pathological findings, confined to the cerebral hemisphere homolateral to the
      facial hemiatrophy, and including monoventricular enlargement, meningo-cortical
      dysmorphia and white matter changes. CONCLUSIONS: The MR morphology, and
      corresponding neuroradiological and histopathological findings disclosed by a
      review of the literature, indicate that homolateral hemiatrophy is a typical
      finding for a subgroup of PFH patients, but do not support the model of a simple
      or nutritive atrophic process. We reconsider chronic localized meningo
      encephalitis with vascular involvement as possible underlying cause of the
      occasional brain involvement in PFH.

PMID- 7575217
TI  - Progressive apraxia in clinically discordant monozygotic twins.
AB  - OBJECTIVE: To determine disease concordancy in the first identical twin with
      corticobasal degeneration. The patients were 63-year-old, erythrocyte antigen
      confirmed monozygotic male twins who were clinically discordant for progressive
      apraxia caused by corticobasal degeneration. INTERVENTIONS: Neuropsychologic and
      kinesiologic testing, magnetic resonance imaging, and positron emission
      tomographic measurements of cerebral metabolic rate for glucose. RESULTS: The
      affected twin had lower neuropsychologic and kinesiologic test scores than did
      his brother, particularly on tests sensitive to right-compared with left
      hemisphere function; widespread cerebral atrophy, worst in right parietotemporal
      cortices; and reduced whole-brain cerebral metabolic rate for glucose, worst in
      right posterior cortices. The clinically asymptomatic twin had normal
      neuropsychologic and kinesiologic test scores but performed more poorly on tests
      sensitive to left- compared with right-hemisphere function; had no abnormalities
      on magnetic resonance imaging; and had left temporoparietal as well as mild whole
      brain hypometabolism. CONCLUSIONS: Corticobasal degeneration may remain
      clinically discordant in identical twins after 7 years. Positron emission
      tomography and neuropsychologic findings suggest the possibility of a preclinical
      stage of corticobasal degeneration. There is generalized cortical atrophy in
      patients with corticobasal degeneration in addition to focal atrophy.

PMID- 7575218
TI  - Tau, ubiquitin, and alpha B-crystallin immunohistochemistry define the principal
      causes of degenerative frontotemporal dementia.
AB  - OBJECTIVE: We investigated the use of immunostaining with antibodies to tau,
      ubiquitin, and alpha B-crystallin in defining a protocol for the staged
      neuropathologic examination of brains from patients with a progressive
      frontotemporal dementia. DESIGN: Brains obtained from 50 patients dying with the
      clinical diagnosis of frontotemporal dementia were examined histopathologically
      to define pathologic distinctions. SETTING: Two university hospital
      neuropathology departments. RESULTS: Anti-tau immunostaining defined corticobasal
      degeneration, Alzheimer's disease, and Pick's disease; antiubiquitin defined
      motor neuron disease with dementia. The remaining brains have frontal lobe
      degeneration: the use of alpha B-crystallin immunostaining, on these, to detect
      ballooned neurons may help to define two groups of patients, one of which we
      believe may represent a variant of Pick's disease. CONCLUSION: These findings
      indicate that immunostaining with these antibodies is essential for the
      evaluation of frontal dementia.

PMID- 7575219
TI  - Starnberg trial on epidemiology of Parkinsonism and hypertension in the elderly.
      Prevalence of Parkinson's disease and related disorders assessed by a door-to
      door survey of inhabitants older than 65 years.
AB  - OBJECTIVE: To investigate the prevalence of different types of parkinsonism (PS)
      in the elderly, regardless of health care service or drug prescription, by a door
      to-door survey in two German villages. DESIGN: We investigated the prevalence of
      PS in a rural Bavarian population of individuals older than 65 years (982
      participants; response rate, 82.5%) using a door-to-door-survey and a biphasic
      approach. MAIN OUTCOME MEASURES: Two investigators employed a pretest screening
      questionnaire and motor tests for signs of PS. Individuals suspected of suffering
      from PS were reinvestigated by two neurologists trained in movement disorders,
      and computed tomographic scans were performed. RESULTS: The prevalence of
      Parkinson's disease in individuals older than 65 years was 0.71% (95% confidence
      interval, 0.19% to 1.23%), with a male predominance (five men, two women).
      Parkinsonism of other pathogenesis included drug-induced PS (0.41%, four of 982
      inhabitants), vascular PS (0.20%, two of 982), multiple system atrophy (0.31%,
      three of 982), and Fahr's disease (0.10%, one of 982). The high prevalence of
      normal-pressure hydrocephalus (0.41%, four of 982 inhabitants) was an unexpected
      finding that was confirmed by computed tomography. Fifty percent of cases of PS
      were newly diagnosed. CONCLUSIONS: This study represents the first door-to-door
      survey on PS in Germany. In addition, for the first time, it includes a clinical
      differentiation between Parkinson's disease, multiple system atrophy (of the
      striatonigral type), and PS of other pathogenesis. The prevalence of Parkinson's
      disease corresponds to that reported in other surveys of people older than 65
      years. Normal-pressure hydrocephalus and multiple system atrophy, on the other
      hand, were more prevalent than expected, and all these cases were newly
      diagnosed.

PMID- 7575220
TI  - Medical treatment of cysticercosis: ineffective vs effective.

PMID- 7575221
TI  - Assessing the competency of patients with Alzheimer's disease under different
      legal standards. A prototype instrument.
AB  - OBJECTIVE: To assess empirically the competency of patients with Alzheimer's
      disease (AD) to consent to medical treatment under different legal standards
      (LSs). DESIGN: Comparison of normal older subjects and patients with AD on
      measures of competency to consent to medical treatment. SETTING: University
      medical center. SUBJECTS: Normal older control subjects (n = 15) and patients
      with probable AD (n = 29 [15 with mild and 14 with moderate AD]). MAIN OUTCOME
      MEASURES: Two specialized clinical vignettes were developed that test a subject's
      capacity to consent to medical treatment under five well-established LSs for this
      competency: LS1, evidencing treatment choice; LS2, making the reasonable choice;
      LS3, appreciating consequences of choice; LS4, providing rational reasons for
      choice; and LS5, understanding treatment situation and choices. Performance on
      the LSs was compared across control and AD groups using Student's t test, chi 2,
      and analysis of variance. Demented subjects were categorized as competent,
      marginally competent, or incompetent under each LS by using a cutoff score
      derived from normal control performance. RESULTS: No differences between groups
      emerged for LS1 and LS2. Control subjects performed significantly better than
      patients with mild AD on LS4 and LS5, and significantly better than patients with
      moderate AD on LS3, LS4, and LS5. Patients with mild AD performed significantly
      better than patients with moderate AD on LS4 and LS5. With respect to competency
      status, patients with AD showed a consistent and progressive pattern of
      compromise (marginal competence or incompetence) related to dementia severity and
      stringency of the LS. CONCLUSIONS: A reliable prototype instrument validly
      discriminated the competency performance and classified the competency status of
      control subjects and patients with mild and moderate AD under five LSs for
      competency to consent to medical treatment. While the groups performed
      equivalently on minimal standards requiring merely a treatment choice (LS1) or
      the reasonable treatment choice (LS2), patients with mild AD had difficulty with
      more difficult standards requiring rational reasons (LS4) and understanding
      treatment information (LS5), and patients with moderate AD had difficulty with
      appreciation of consequences (LS3), rational reasons (LS4), and understanding
      treatment (LS5). The results raised the concern that many patients with mild AD
      may not be competent to consent to treatment and supported the value of
      standardized clinical vignettes for assessment of competency in dementia.

PMID- 7575222
TI  - Neuropsychologic predictors of competency in Alzheimer's disease using a rational
      reasons legal standard.
AB  - OBJECTIVE: To identify neuropsychologic predictors of competency performance and
      status in Alzheimer's disease (AD) using a specific legal standard (LS). This
      study is a follow-up to the competency assessment research reported in this issue
      of the archives. DESIGN: Univariate and multivariate analyses of independent
      neuropsychologic test measures with a dependent measure of competency to consent
      to treatment. SETTING: University medical center. SUBJECTS: Fifteen normal older
      control subjects and 29 patients with probable AD. MAIN OUTCOME MEASURES:
      Subjects were administered a battery of neuropsychologic measures theoretically
      linked to competency function, as well as two clinical vignettes testing their
      capacity to consent to medical treatment under five different LSs. The present
      study focused on one specific LS: the capacity to provide "rational reasons" for
      a treatment choice (LS4). Neuropsychologic test scores were correlated with
      scores on LS4 for the normal control group and the AD group. The resulting
      univariate predictors were then analyzed using stepwise regression and
      discriminant function to identify the key multivariate predictors of competency
      performance and status under LS4. RESULTS: Measures of word fluency predicted the
      LS4 scores of controls (R2 = .33) and the AD group (R2 = .36). A word fluency
      measure also emerged as the best single predictor of competency status for the
      full subject sample (n = 44), correctly classifying 82% of cases. Dementia
      severity (Mini-Mental State Examination score) did not emerge as a multivariate
      predictor of competency performance or status. Interestingly, measures of verbal
      reasoning and memory were not strongly associated with LS4. CONCLUSIONS: Word
      fluency measures predicted the normative performance and intact competency status
      of older control subjects and the declining performance and compromised
      competency status of patients with AD on a "rational reasons" standard of
      competency to consent to treatment. Cognitive capacities related to frontal lobe
      function appear to underlie the capacity to formulate rational reasons for a
      treatment choice. Neuropsychologic studies of competency function have important
      theoretical and clinical value.

PMID- 7575223
TI  - A standardized technique for establishing onset and duration of symptoms of
      Alzheimer's disease.
AB  - OBJECTIVES: To develop an informant-based semistructured interview to determine
      the onset and duration of symptoms of Alzheimer's disease, and to use this
      instrument with informants to characterize a cohort of mildly impaired patients
      with Alzheimer's disease. DESIGN: In study 1, interrater and interinformant
      reliability was examined for the date of onset and the order of appearance for
      specific symptoms that were elicited by the semistructured onset interview. In
      study 2, the instrument was used to characterize disease onset in a cohort of
      patients with Alzheimer's disease who were participating in a large multicenter
      study. SUBJECTS: Informants of patients with Alzheimer's disease. RESULTS: In
      study 1, interrater reliability for duration of illness was excellent (intraclass
      correlation coefficient = .99, P < .001), and interinformant reliability was good
      (intraclass correlation coefficient = .86, P < .001). Agreement for the presence
      of a given symptom was highest for those that were most commonly reported (eg,
      memory and performance difficulty). In study 2, 89% of the cohort had memory
      problems, and 63.9% had performance difficulties as the first or second symptom.
      Depression and language problems were less commonly reported. Psychosis and
      behavioral disturbances were rarely reported as the first problem. CONCLUSION:
      This instrument provides a reliable procedure for standardizing the estimation of
      duration of illness based on retrospective report.

PMID- 7575224
TI  - White matter lesions and disequilibrium in older people. I. Case-control
      comparison.
AB  - OBJECTIVE: To investigate the relationship between subcortical white matter
      lesions identified on magnetic resonance imaging and gait and balance problems in
      older people. DESIGN: Magnetic resonance imaging scans of the brain in 27
      community-dwelling older patients (> 75 years of age) who had subjective and
      objective abnormalities of gait and balance of unknown cause were compared with
      those of 27 age- and sex-matched control subjects. The T2-weighted intense
      lesions of the subcortical white matter were graded on a scale of 0 to 2.
      SETTING: Outpatient clinic. RESULTS: The patient had significantly (P < .01, chi
      2) more severe subcortical white matter hyperintensities on magnetic resonance
      imaging than did the control group. Patients fell more frequently than did the
      control subjects and had slower motor responses and prolonged reaction times
      compared with the control subjects. CONCLUSIONS: Subcortical white matter lesions
      identified on magnetic resonance imaging are associated with gait and balance
      dysfunction in ambulatory older people. These lesions probably interfere with
      central processing of sensorimotor signals leading to impaired postural
      responses.

PMID- 7575225
TI  - White matter lesions and disequilibrium in older people. II. Clinicopathologic
      correlation.
AB  - OBJECTIVE: To identify the cause of subcortical white matter lesions seen on
      magnetic resonance imaging in older patients with progressive deterioration of
      gait and balance. DESIGN: Postmortem examination of three patients with objective
      impairment of gait and balance thought to be due to subcortical white matter
      lesions identified on magnetic resonance imaging. Brain sections were stained
      with routine methods and for glial fibrillary acid protein using an
      immunoperoxidase technique. PATIENTS: Part of a prospective study of gait and
      balance problems in older people. None had a history of hypertension or discrete
      strokelike episodes. RESULTS: Other than a few small infarcts in the basal
      ganglia and internal capsule in the patient with the mildest gait disorder, there
      were no gross or microscopic features on routine examination post mortem to
      explain the white matter hyperintensities on magnetic resonance imaging or the
      progressive gait deterioration. By contrast, immunohistochemical staining with
      anti-glial fibrillary acid protein showed prominent astrocytosis T2-weighted high
      intensity signal areas on magnetic resonance imaging. CONCLUSIONS: The astrocytes
      presumably swell as they take up extravasated protein at the site of a breakdown
      in the blood-brain barrier, and the increased water content per unit volume
      increases the magnetic resonance imaging proton signal. We hypothesized that the
      astrocytes may have been initially activated by small infarcts or subclinical
      ischemia, but the process then became self-perpetuating, ultimately involving
      most of the white matter and producing the severe gait disorder.

PMID- 7575226
TI  - Use of buspirone for treatment of cerebellar ataxia. An open-label study.
AB  - OBJECTIVE: To evaluate the efficacy of buspirone hydrochloride, a serotonin (5
      hydroxytryptamine1A) agonist, in treating patients with cerebellar ataxia.
      DESIGN: Open-label study in which 20 patients (14 with cerebellar cortical
      atrophy and six with olivopontocerebellar atrophy) received buspirone
      hydrochloride, up to 60 mg/d, for 8 weeks. SETTING: Research hospital. MAIN
      OUTCOME MEASURES: Clinical, physiological, and psychological assessment. RESULTS:
      Nine patients with mild or moderate cerebellar dysfunction who completed the
      study showed significant improvement in clinical and self-assessment ratings, but
      not in a motor performance test, posturography (data were incomplete), State
      Trait Anxiety Inventory, and Beck Depression Inventory. Seven patients with
      severe cerebellar dysfunction who completed the study had no improvement on any
      measure. CONCLUSIONS: Buspirone may be effective in treating mild to moderate
      cerebellar ataxia. A double-blind study of the efficacy of buspirone in
      cerebellar ataxia is warranted.

PMID- 7575229
TI  - Instruction by retinoic acid of incisor morphology in the mouse embryonic
      mandible.
AB  - Endogenous retinoids are present in the embryonic mouse mandible and reach a peak
      in concentration at the time of the formation of the dental lamina. All-trans
      retinoic acid is present in a 10-fold higher concentration in the future incisor
      region of the mouse embryonic mandible at day 11.5. It was found here that
      exogenous all-trans retinoic acid has pleiotropic effects on the pattern of
      odontogenesis when applied before the formation of the dental lamina. These
      effects include a change in the pattern of the dental lamina, supernumerary buds
      and incisors in the diastema region, and replacement of molars with incisors in
      the molar region. Thus retinoic acid appears to instruct incisor morphology in
      the mouse embryonic mandible.

PMID- 7575228
TI  - The relationship of neuropsychological functioning to quality of life in
      epilepsy.
AB  - OBJECTIVE: To examine the relationship of objectively assessed cognitive
      functioning to self-reported quality of life. DESIGN: Correlational, multiple
      regression, and factor analytic comparisons of a new self-report quality of life
      inventory with neuropsychological tests of cognition and mood. SUBJECTS: Two
      hundred fifty-seven patients with epilepsy. SETTING: Twenty-five epilepsy centers
      and neurology clinics across the United States. MEASURES: A recently developed
      self-report (ie, Quality of Life in Epilepsy-89 inventory) and objective tests of
      memory, verbal abilities, spatial functions, psychomotor and cognitive processing
      speed, cognitive flexibility, and mood. RESULTS: Factors that assessed mood,
      psychomotor speed, verbal memory, and language correlated significantly with
      selected scales of the Quality of Life in Epilepsy-89 inventory (P < .0001) and
      were predictive of overall quality of life (P < .002 to P < .0001). The mood
      factor showed the highest correlations (r = -.20 to r = -.73) and was the
      strongest predictor of quality of life in regression analyses (46.7% explained
      variance, P < .0001). CONCLUSIONS: Mood may be adversely affected by diminished
      quality of life, or perceived quality of life may be affected by mood
      disturbance. Quantitative quality of life assessments can be used in conjunction
      with formal neuropsychological testing of mood and cognition when evaluating
      patients with epilepsy.

PMID- 7575230
TI  - Extraordinary diphyodonty-related change in dental function for a tooth of the
      extinct marsupial Ekaltadeta ima (Propleopinae, Hypsiprymnodontidae).
AB  - A time-dependent, fundamental change in function for a sectorial tooth in a group
      of extinct, propleopine kangaroos is reported. In juvenile Ekaltadeta ima
      (Marsupialia, Hypsiprymnodontidae, Propleopinae) the second premolar (P2)
      functions as a serrated blade at the anterior end of the cheek tooth row. In
      adults, this tooth drops far below the occlusal plane of the cheek tooth row
      where it assumes a completely different function, that of a buttress,
      anterolingual to the base of the crown of the much larger, newly erupted third
      premolar (P3). This pattern of diphyodonty-related change in dental function is
      unique within Mammalia. It also represents an extraordinary example of biological
      recycling of a normally discarded tooth.

PMID- 7575227
TI  - Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed
      epilepsy. A randomized, controlled study.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and cognitive effects of initial
      vigabatrin monotherapy compared with initial carbamazepine monotherapy in
      patients with newly diagnosed epilepsy. DESIGN: Open, randomized, controlled
      design. Follow-up period of 12 months. SETTING: University hospital with an
      epilepsy center. PATIENTS: A total of 100 patients, aged 15 to 64 years,
      classified as suffering from partial seizures and/or generalized tonic-clonic
      seizures were randomized to either vigabatrin or carbamazepine monotherapy. Fifty
      nine patients with a single epileptic seizure and no antiepileptic drug treatment
      served as a control population for objective safety measures. OUTCOME MEASURES:
      To evaluate the comparative efficacy and toxicity of vigabatrin and
      carbamazepine, the drug success rate (ie, the proportion of patients continuing
      successful treatment with the randomly assigned drug) after 12 months of steady
      state treatment was used. To evaluate the safety of the drugs in addition to
      reported side effects, visual evoked potential recordings and neuropsychological
      evaluation were performed during follow-up. RESULTS: During the 12-month follow
      up period, 60% of patients receiving vigabatrin and carbamazepine were treated
      successfully. Vigabatrin caused fewer side effects that required discontinuation
      of therapy. However, vigabatrin had to be discontinuated more often owing to lack
      of efficacy, and fewer of the successfully treated patients receiving vigabatrin
      achieved total freedom from seizures. Vigabatrin had no detrimental effects on
      cognitive functions. Retrieval from both episodic and semantic memory and
      flexibility of mental processing improved significantly in patients successfully
      treated with vigabatrin. CONCLUSION: Vigabatrin seems to be an effective and safe
      antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side
      effects than carbamazepine.

PMID- 7575231
TI  - Reduced CD8+ peripheral blood T lymphocytes in rapidly progressive periodontitis.
AB  - The peripheral blood T-cell phenotype of patients with rapidly progressive
      periodontitis (RPP) was determined in order to investigate whether there were T
      cell imbalances or not. Twenty patients aged 21-39 yr were selected for this
      study. Bone resorption and probing pocket depth were measured. All the patients
      had 10 or more teeth showing bone loss of 50% or more. As controls, 12
      periodontally healthy, age-matched individuals were selected. Blood samples were
      obtained by venipuncture, and lymphocytes were isolated. Two-colour flow
      cytometric analysis was done with monoclonal antibodies against human CD4, CD8,
      and CD45RA antigens. The RPP patients were found to have significantly lower
      percentage of CD8+ T cells (Mann-Whitney's U-test, p < 0.01) and an increased
      CD4/CD8 ratio (Mann-Whitney's U-test, p < 0.01) compared with healthy
      individuals. On the other hand, there were no significant differences in the
      percentages of CD4+ T cells and CD4+ CD45RA+ T cells between RPP patients and
      healthy individuals. No correlations between the clinical findings and T-cell
      subsets were found. These findings suggest that imbalances of peripheral blood T
      lymphocytes, especially a tendency to decreased CD8 + T cells, exist in RPP
      patients, and that cellular immune responses mediated by CD8 + T cells may play a
      part in the pathogenesis of RPP.

PMID- 7575232
TI  - Immunohistochemical study on the immunocompetent cells of the pulp in human non
      carious and carious teeth.
AB  - The condition of the pulp tissue was classified into seven groups according to
      the depth of carious lesions from stage (S) 0 (non-carious teeth) to S6 (exposed
      pulp). A substantial change in the infiltration of immunocompetent cells occurred
      between S3 and S4; all types were markedly increased in S4 as compared to S3,
      with a remarkable increase in the number of helper T lymphocytes, B-lineage
      cells, neutrophils and macrophages. Therefore, the pulpal immune reaction to
      carious stimuli could be classified into early (S1-S3) and advanced phases (S4
      S6). In the early phase a cellular immunoresponse would be induced by T-lineage
      cells, and in the advanced phase the humoral immunoresponse is furthered by B
      lineage cells concomitant with the destruction of pulp tissue by proteolytic
      enzymes released from infiltrating neutrophils and macrophages. Human dental pulp
      is thus equipped with a functional immune response that is sufficient as a
      biodefensive mechanism. Dental caries should be treated before S4.

PMID- 7575233
TI  - The effects of smokeless tobacco extract on bone nodule formation and
      mineralization by chick osteoblasts in vitro.
AB  - Short-term exposure to smokeless tobacco extracts (STE) reportedly inhibits
      osteoblast metabolism. The objective of this study was to determine the effects
      of serial dilutions of a water-soluble extract of smokeless tobacco on osteoblast
      proliferation and their potential to form and mineralize bone nodules. STE
      significantly stimulated cell proliferation when diluted 10(2)-10(4) times; 10(3)
      and 10(4) dilutions produced the greatest effect. 10(2)-10(4) STE dilutions
      significantly increased alkaline phosphatase activity at day 7 but 10(6) STE
      dilutions significantly decreased it. 10(3) and 10(4) dilutions significantly
      increased bone nodule formation, but inhibited their mineralization. In contrast,
      10(5) and 10(6) dilutions significantly decreased bone nodule formation, but
      increased their mineralization. Stimulation of in vitro bone nodule formation by
      STE was similar to that produced by 10(-7) M insulin-like growth factor 1 (IGF-1)
      in vivo. Heat and acid treatment of STE significantly reduced its beneficial
      effect on cell proliferation, suggesting that a peptide within STE may be
      responsible for enhancement of osteogenic cell proliferation. Thus, STE may
      contain a peptide capable of significantly stimulating osteoblast proliferation,
      differentiation and metabolism, similar to the effects of IGF-1. This peptide
      could have potential therapeutic benefits.

PMID- 7575234
TI  - The application of Moire magnification to high-resolution studies of human
      premolar eruption.
AB  - The optical phenomenon of Moire magnification can be used to provide real-time
      measurements of the position of an erupting human premolar, with a resolution of
      0.1 micron or better. A new instrument for this purpose, which allows repeated
      measurements in the same individual, is described. Cyclic changes in the position
      of the erupting tooth in concert with the heartbeat, with a magnitude of 0.05
      0.35 micron, can be discerned. An unusual cyclic rhythm, with a period of 20-50
      s, was observed.

PMID- 7575235
TI  - Odontogenic tumours in the v-Ha-ras (TG.AC) transgenic mouse.
AB  - A line of homozygous transgenic mice (TG.AC) carrying a v-Ha-ras gene fused to
      the promoter of the zeta globin gene produces a variety of mesenchymal and
      epithelial neoplasms including odontogenic tumours. The 1-year incidence of
      odontogenic tumour formation in these mice was approx. 35%. Tumours formed more
      often in the mandible than maxilla. The various types of tumours frequently
      presented with: (1) primarily mesenchymal cells in a dense fibrous-like matrix,
      or (2) loose stroma surrounded by anastomosing cords of epithelial cells that
      exhibited squamous differentiation, or (3) odontomas forming mineralized tooth
      structures by well-differentiated odontoblasts and ameloblasts. Some tumours had
      areas with all three of these characteristics. Mineralized dentine and enamel in
      the odontomas were morphologically similar to those of normal murine teeth.
      Odontogenic tumours expressed the v-Ha-ras transgene that was primarily localized
      to the mesenchymal cells. Proliferating-cell nuclear antigen immunohistochemistry
      showed that the mesenchymal cells adjacent to the epithelial cords not only
      expressed the ras transgene but were also actively proliferating. The TG.AC mouse
      provides an excellent model for the study of odontogenic tumours and tooth
      development.

PMID- 7575236
TI  - Expression of a functional rat salivary cystatin S polypeptide in Escherichia
      coli.
AB  - Cystatin S is a cysteine proteinase inhibitor that is transiently expressed
      during rat submandibular gland development and can be induced by isoproterenol in
      the adult. A cDNA for rat cystatin S which included the entire coding sequence of
      the secreted cystatin was cloned. A coding region of the cystatin gene was
      amplified by polymerase chain reaction and cloned into the pGEX-2T expression
      vector. The chimeric plasmid was transformed into Escherichia coli, and protein
      expression was induced by isopropyl-beta-D-thiogalactopyranoside. The expressed
      protein was purified from insoluble inclusion bodies after solubilization with
      urea and fast protein liquid chromatography on a MonoQ column. The purified
      recombinant cystatin reacted with antibodies to cystatin S purified from rat
      submandibular glands and showed an amino-terminal amino acid sequence identical
      to that of rat cystatin S. The recombinant protein exhibited papain inhibition
      activity comparable to natural cystatin. This was a successful expression and
      purification of a functionally and immunologically reactive recombinant cystatin
      from E. coli, an approach which will be used later towards generating recombinant
      variants to study the binding and functional domains of this cysteine protease
      inhibitor.

PMID- 7575237
TI  - Blockade of the initiation of murine odontogenesis in vitro by citral, an
      inhibitor of endogenous retinoic acid synthesis.
AB  - Endogenous retinoids are present in the embryonic mouse mandible and reach a
      concentration peak immediately before the formation of the dental lamina. Because
      exogenous retinoids alter the pattern of the dental lamina and the expression of
      epidermal growth factor mRNA (a transcript necessary for initiation of
      odontogenesis), the role of retinoic acid in the initiation of odontogenesis was
      studied here. Citral (3,7-dimethyl-2,6-octadienal), a known inhibitor of retinoic
      acid synthesis, was used to block the endogenous synthesis of retinoic acid in
      the mouse embryonic mandible before the formation of the dental lamina
      (gestational day 9). A 24-h exposure to citral totally blocked tooth formation in
      7/10 mandibles. Reductions of endogenous retinoic acid concentrations were
      confirmed by high-performance liquid chromatography. Tooth formation was restored
      by simultaneous treatment with all-trans retinoic acid or 9-cis retinoic acid
      during the citral exposures (first 24 h of culture). Endogenous retinoic acid is
      necessary for the initiation of odontogenesis.

PMID- 7575238
TI  - Immunolocalization of bone matrix macromolecules in human tissues regenerated
      from periodontal defects treated with expanded polytetrafluoroethylene membranes.
AB  - Guided tissue regeneration (GTR) is a concept that evolved from the development
      of membrane barrier techniques which allow the repopulation of periodontal wounds
      by desirable cells, resulting in a so-called new attachment apparatus. To
      understand the biological mechanisms involved in membrane barrier-led periodontal
      healing, the histological localization of macromolecules phenotypical of bone and
      cementum formation was investigated in regenerating human periodontal tissues
      harvested after healing by placing barriers on teeth untreatable except by
      extraction. Using immunolocalization techniques, frozen sections of soft tissues
      and hard tissues under GTR barriers were stained with antibodies to osteonectin
      (LB-BON-II) and bone sialoprotein (BSP) (LF-6); alkaline phosphatase (AP) was
      detected histochemically. Frozen sections of regenerating periodontal tissue
      demonstrated the presence of spindle-shaped, fibroblast-like cells entrapped in a
      dense fibrillar extracellular matrix. Rounded cells aggregated to form nodules
      heavily stained by the Alcian blue method, indicating the presence of
      proteoglycans and strongly resembling those noted in hard-tissue sections. At the
      electron-microscopic level, the cytoplasm of the elongated cells had numerous
      cisternae of endoplasmic reticulum and Golgi saccules, indicating metabolic
      activity. Striated collagen fibres were scattered throughout the field of the
      sections. AP-stained soft-tissue sections demonstrated the presence cell-bound
      and extracellular AP. Osteonectin antibody staining confirmed the presence of
      this macromolecule in the extracellular matrix, particularly in the area of the
      cellular nodules. The dense network of connective tissue fibres was also
      stained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575239
TI  - Basal levels of noradrenaline, dopamine, 5-hydroxytryptamine, and acetylcholine
      in the submandibular, parotid, and sublingual glands of mice and rats.
AB  - The salivary glands of 5-week-old mice and rats were divided into submandibular,
      parotid, and sublingual and analysed to determine basal levels of the
      neurotransmitters noradrenaline (NE) and acetylcholine (ACh) and the possible
      neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT), using a
      combination of high-performance liquid chromatography coupled with coulometric
      and amperometric detection and a direct injection technique employing crude
      homogenate supernatants. In both species, levels of NE were higher in the
      submandibular than in the other salivary glands, whereas levels of ACh were
      higher in the mouse submandibular and the rat sublingual glands than in other
      glands. In all the salivary glands, levels of DA were markedly lower than those
      of other target substances. Levels of 5-HT were similar in all salivary glands.
      These results show that in mouse and rat salivary glands, species differences in
      neurotransmitter distribution are relatively small, whereas there are
      considerable differences in distribution between the salivary glands.

PMID- 7575240
TI  - Ultrastructural relation between nerve terminals and dentine bridge formation
      after pulpotomy in human teeth.
AB  - Close association between nerve terminals and preodontoblasts, odontoblasts and
      predentine was observed during healing after pulpotomy. The nerve terminals
      frequently contained large numbers of synaptic vesicles. Terminals with many
      vesicles tended to be fewer in the predentine than in the odontoblastic layer.
      The distribution of terminals was more dense at the stage before the regenerated
      odontoblasts became arranged regularly beneath the predentine. It is suggested
      that these terminals have some efferent role(s), especially during collagen
      synthesis at the early stage of dentinogenesis. The nerves may release their
      abundant synaptic vesicles, in addition to serving a sensory role for monitoring
      the increased sensitivity in the injured areas.

PMID- 7575241
TI  - A histochemical study of apoptosis in the reduced ameloblasts of erupting mouse
      molars.
AB  - Apoptotic reactions were demonstrated with a commercial detection kit in the
      reduced ameloblasts around the tip of the cusp just before and after exposure to
      the mouth but, as tooth eruption advanced, they were no longer seen in the
      remainder of the reduced ameloblasts. Although some of the reduced ameloblasts
      appear to be expelled as a consequence of apoptosis, the remainder appear to
      constitute the junctional epithelium.

PMID- 7575242
TI  - Transdentinal stimulation of reparative dentine formation by osteogenic protein-1
      in monkeys.
AB  - Recombinant human osteogenic protein-1 (OP-1) when applied to freshly cut dentine
      stimulated significantly more reparative dentine than calcium hydroxide paste in
      permanent monkey teeth. The response to OP-1 was dependent upon the concentration
      applied to the tooth as a cavity liner as well as the thickness of the residual
      dentine. The response to calcium hydroxide was similarly dependent upon the
      thickness of the residual dentine. These data suggest that dental pulps contain
      cells, including perhaps mature odontoblasts, responsive to OP-1. Therefore OP-1
      may be useful in the therapeutic induction of reparative dentine formation.

PMID- 7575243
TI  - Prospective Evaluation of Radial Keratotomy (PERK) Study 10 years after surgery.

PMID- 7575244
TI  - Astigmatism Reduction Clinical Trial.

PMID- 7575245
TI  - Herpes simplex virus in iridocorneal endothelial syndrome.

PMID- 7575246
TI  - Magnetic resonance imaging in patients with low-tension glaucoma.

PMID- 7575247
TI  - New cases of crystalline deposits on intraocular lenses not related to any
      specific viscoelastic.

PMID- 7575248
TI  - Retinal toxic effects following inadvertent intraocular injection of Celestone
      Soluspan.

PMID- 7575249
TI  - Bilateral acute angle-closure glaucoma associated with drug sensitivity to
      hydrochlorothiazide.

PMID- 7575250
TI  - Marked intraocular pressure rise following blood injection into a filtering bleb.

PMID- 7575251
TI  - Ocular lymphoma diagnosed by internal subretinal pigment epithelium biopsy.

PMID- 7575253
TI  - Is laser sclerostomy surgery ready for 'prime time'?

PMID- 7575252
TI  - Variations in preoperative medical testing in healthy cataract surgery patients.

PMID- 7575254
TI  - Photoreceptor apoptosis in animal models. Implications for retinitis pigmentosa
      research.

PMID- 7575255
TI  - Do ophthalmologists, anesthesiologists, and internists agree about preoperative
      testing in healthy patients undergoing cataract surgery?
AB  - To assess variation in reported use of preoperative medical tests in patients
      undergoing cataract surgery and to identify factors that influence test use by
      different physician groups we performed a national survey of ophthalmologists,
      anesthesiologists, and internists. Participants included randomly selected
      members of American professional societies who provided care to one or more
      patients undergoing cataract surgery in 1991. Responses were obtained from 538
      (82%) of 655 eligible ophthalmologists, 109 (76%) of 143 anesthesiologists, and
      54 (44%) of 122 internists. Fifty percent of ophthalmologists, 40% of internists,
      and 33% of anesthesiologists frequently or always obtained a chest x-ray film,
      while 20% of ophthalmologists, 27% of internists, and 37% of anesthesiologists
      never obtained a chest x-ray film for patients being considered for cataract
      surgery who had no history of major medical problems (P < .01 for differences
      between ophthalmologists and the other groups). Similarly, 70% to 90% of
      ophthalmologists, 73% to 79% of internists, and 41% to 79% of anesthesiologists
      frequently or always obtained a complete blood cell count, electrolyte panel, and
      electrocardiogram, while 4% to 11% of ophthalmologists, 13% to 17% of internists,
      and 9% to 28% of anesthesiologists never obtained these tests for such patients.
      Many respondents (32% to 80%) believed tests were unnecessary but cited multiple
      reasons for obtaining tests (eg, medicolegal concerns and institutional
      requirements). Many physicians in each group viewed preoperative evaluations as
      screening opportunities or believed that one of the other two types of physicians
      "required" tests. We conclude that marked variation exists within and across
      physician specialties in the use and rationale for use of medical tests in
      patients undergoing cataract surgery.

PMID- 7575256
TI  - Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial
      keratitis. Report from the Bacterial Keratitis Study Research Group.
AB  - PURPOSE: To compare ofloxacin solution with a combination of fortified antibiotic
      cefazolin sodium and tobramycin sulfate solutions in the treatment of bacterial
      keratitis. METHODS: Patients under care at any one of 28 participating clinical
      centers who had an eye with suspected bacterial keratitis were randomly allocated
      in a double-masked manner to treatment with 0.3% ofloxacin solution or a
      combination of the fortified antibiotics (1.5% tobramycin and 10.0% cefazolin
      solutions). MAIN OUTCOME MEASURES: Time to healing defined as complete re
      epithelization, accompanied by a nonprogressive stromal infiltrate for two
      consecutive visits. Secondary outcome measures included patient symptoms and
      signs of infection and adverse reactions to study medications. Only patients with
      a positive bacterial corneal culture were included in most analyses. RESULTS: A
      positive bacterial corneal culture was obtained in 140 (56%) of the 248 enrolled
      patients. The time to healing was similar among the 73 patients receiving
      ofloxacin and the 67 patients receiving fortified antibiotics (P = .70). By 7
      days after study entry, the keratitis in 37% of the ofloxacin group and 38% of
      the fortified antibiotics group had healed. By 28 days, keratitis in 89% of the
      ofloxacin group and 86% of the fortified antibiotics group had healed. Two
      patients receiving ofloxacin and one receiving fortified antibiotics discontinued
      study medication because of lack of efficacy. Patients receiving ofloxacin
      reported substantially less burning and stinging on instillation than the
      patients receiving fortified antibiotics (P < .001). Five of six patients among
      the 140 with positive bacterial cultures who had study medications discontinued
      because of ocular side effects were in the fortified antibiotics group; an
      additional three patients, all in the fortified antibiotics group, among the
      remaining 108 receiving study medications had ocular side effects. CONCLUSIONS:
      The efficacy of ofloxacin solution in treating bacterial keratitis is equivalent
      to that of the fortified cefazolin and tobramycin solutions. The reduced
      frequency of ocular toxic effects and the relative ease of preparation of
      ofloxacin are additional considerations.

PMID- 7575257
TI  - Ocular surface changes and discomfort in patients with meibomian gland
      dysfunction.
AB  - OBJECTIVE: To determine the importance of meibomian gland dysfunction (MGD) on
      the ocular surface. DESIGN: Prospective study. SETTING: A university-based
      referral practice. PATIENTS: Patients with ocular discomfort (147 eyes) and
      without ocular discomfort (54 eyes) were examined. In the total 201 eyes, MGD was
      defined as the presence of an obstruction of the meibomian orifices (obstruction
      group [n = 54]) or the absence of a gland structure (gland dropout group [n =
      36]), or both of these findings (combined group [n = 38]). There were not any
      findings of MGD in 73 eyes (non-MGD group). MAIN OUTCOME MEASURES: Scores that
      were obtained from fluorescein and rose bengal staining, the breakup time of the
      tear film, the rates of tear evaporation and tear production, and meibography.
      RESULTS: Of the 147 eyes with ocular discomfort, 95 (64.6%) had either an
      obstruction of an orifice or gland dropout, or both. The combined group had
      higher scores for staining with fluorescein (P = .002) and rose bengal (P = .021)
      compared with that in the non-MGD group. The rate of tear production was
      increased more in the gland dropout group than in the non-MGD group (P = .002).
      The rate of tear evaporation was significantly increased in the gland dropout
      group (P = .017). CONCLUSION: Meibomian gland dysfunction is a major cause of
      ocular surface abnormalities and ocular discomfort.

PMID- 7575258
TI  - Branch retinal arterial occlusions in multifocal retinitis with optic nerve
      edema.
AB  - OBJECTIVE: To determine the natural history and visual prognosis of patients with
      branch retinal arterial occlusions secondary to multifocal retinitis. METHODS:
      Cases were reviewed for seven patients who exhibited multifocal retinitis and
      branch retinal arterial occlusion. The average age of the patients was 27 years
      (age range, 14 to 19 years). RESULTS: Six patients had systemic illnesses
      associated with their ocular findings. Four patients were scratched by a cat or
      exposed to a cat with fleas within 1 month of symptoms. Three of these patients
      were tested and had positive cat-scratch disease titers. At presentation, five
      patients complained of a scotoma, and two noted blurred vision. On examination,
      visual acuity was 20/25 or better in all but one eye. Five patients had vitritis,
      which was bilateral in three. Four patients exhibited optic nerve edema, which
      was bilateral in two. White intraretinal infiltrates were present in all
      patients, and were bilateral in five. The six patients who were examined within 1
      week of symptoms had a white retinal infiltrate at the site of vascular
      occlusion. The retinal findings resolved in 2 to 6 weeks and did not recur. The
      final visual acuity was 20/20 OU in all patients. CONCLUSIONS: Branch retinal
      arterial occlusions represent a complication of multifocal retinitis and
      idiopathic optic nerve edema. The arterial occlusions are probably caused by a
      focus of retinitis. This self-limited disorder has an excellent visual prognosis
      and may be related to cat-scratch disease.

PMID- 7575259
TI  - 2 peripheral scatter photocoagulation for neovascularization associated with pars
      planitis.
AB  - BACKGROUND: Peripheral cryotherapy appears to be efficacious in the treatment of
      neovascularization of the vitreous base in patients with pars planitis, although
      it may be associated with the development of rhegmatogenous retinal detachments.
      OBJECTIVE: To evaluate the safety and efficacy of peripheral scatter
      photocoagulation for treatment of neovascularization of the vitreous base when
      used alone or combined with pars plana vitrectomy. METHODS: Six patients (10
      eyes) presented with vitritis, cystoid macular edema, and neovascularization of
      the vitreous base, unresponsive to corticosteroid therapy. Three patients (five
      eyes) received scatter diode or argon photocoagulation treatment alone. The other
      three patients (five eyes) underwent pars plana vitrectomy coupled with argon or
      diode photocoagulation, placed in three rows, posterior to the area of inferior
      neovascularization of the vitreous base. RESULTS: Pretreatment visual acuity
      ranged from 20/20 to 20/200. All patients were followed up for a minimum of 6
      months. After placement of photocoagulation (with or without concurrent pars
      plana vitrectomy), the neovascularization regressed, inflammation was stabilized,
      and cystoid macular edema improved in all eyes. There were no retinal detachments
      or other complications of treatment. Posttreatment visual acuity ranged from
      20/20 to 20/100. When final visual acuity was 20/40 or less, cataract formation
      was generally responsible. CONCLUSIONS: Peripheral scatter photocoagulation is
      efficacious and appears at least equal to peripheral cryotherapy in causing
      regression of neovascularization of the vitreous base in patients with pars
      planitis.

PMID- 7575260
TI  - Pigmentary irregularities and optic disc edema after heart transplantation.
AB  - OBJECTIVES: To determine the prevalence of chorioretinal lesions and optic disc
      edema after heart transplantation and to study potential associations. DESIGN AND
      PATIENTS: One hundred one patients who had undergone heart transplantation at one
      institution and 19 patients prior to heart transplantation underwent
      ophthalmological examination, including fundus photography. The prevalence of
      fundus lesions was then compared between the two groups. MAIN OUTCOME MEASURE:
      With a standardized protocol, the presence of optic disc edema, chorioretinal
      hyperpigmentation and depigmentation, retinal hemorrhages, cotton-wool lesions,
      and arteriovenous nicking was graded on color transparencies. RESULTS: The
      prevalence of optic disc edema and hypopigmentations was significantly higher
      among the transplant recipients than among the patients prior to heart
      transplantation (31% vs 5%, P = .01, and 55% vs 11%, P < .001, respectively).
      Hyperpigmentation was only present in patients after transplantation (15% vs 0%,
      P = .06). Heart transplant recipients showed an increased risk of
      hyperpigmentations after 2.5 years. Acute rejection episodes were not associated
      with posterior pole lesions. CONCLUSION: Common posterior pole lesions after
      heart transplantation are optic disc edema and pigmentary changes. Although
      visual acuity does not seem severely impaired, further longitudinal study is
      necessary to evaluate the long-term significance of these lesions.

PMID- 7575261
TI  - Enlargement of the tensor intermuscularis muscle in Graves' ophthalmopathy. A
      computed tomographic and magnetic resonance imaging study.
AB  - OBJECTIVE: To determine whether the tensor intermuscularis muscle (TIM), which
      consists of muscle fibers in the superolateral intermuscular orbital septum, is
      involved in Graves' ophthalmopathy (GO). DESIGN: The computed tomographic (n =
      24) and magnetic resonance imaging (n = 10) appearances of the TIM were
      retrospectively examined in 34 patients with known GO. The severity of GO was
      assessed by applying a scoring system from 0 to 3 (ie, normal [0], mild [1],
      moderate [2], and severe [3]) to each of the rectus muscles and superior oblique
      muscle. The severity of exophthalmos, enlargement of the superior ophthalmic
      vein, and displacement of the lacrimal gland were also recorded. RESULTS: The TIM
      appeared as thickening of the septum immediately behind the globe, and it was
      best seen on coronal magnetic resonance images. There was enlargement of the TIM
      in 19 of the 34 patients, and it was bilateral in 17. Enlargement was present
      only in patients with moderate or severe involvement of other muscles (muscle
      index, > 7/15), and it was significantly correlated with the muscle index (P <
      .05), exophthalmos (P < .05), enlargement of the superior ophthalmic vein (P <
      .005), and anterior displacement of the lacrimal gland (P < .01). Severe
      enlargement of the TIM was seen in only five of the 34 patients, and it showed a
      close correlation with the muscle index (P < .005), exophthalmos (P < .001),
      enlargement of the superior ophthalmic vein (P < .001), and anterior displacement
      of the lacrimal gland (P < .001). CONCLUSIONS: Enlargement of the TIM in GO can
      be identified on computed tomographic and magnetic resonance imaging scans. It is
      invariably associated with moderate or severe involvement of other extraocular
      muscles, and it correlates closely with other well-recognized imaging features of
      severe GO.

PMID- 7575262
TI  - Loss of vertical palpebral fissure height on downgaze in acquired blepharoptosis.
AB  - OBJECTIVE: To determine criteria to diagnose and document functional visual
      impairment from upper eyelid ptosis in the downgaze position of reading. DESIGN:
      Prospective clinical study. PATIENTS: From September 1991 to June 1992, 47
      consecutive patients with adult-onset acquired ptosis were enrolled in the study.
      Downgaze eyelid and relative brow position were evaluated in 88 eyelids of these
      patients. INTERVENTIONS: Surgical repair of blepharoptosis by the Muller muscle
      conjunctival resection ptosis procedure, levator aponeurosis advancement and/or
      resection, or levator muscle resection. MAIN OUTCOME MEASURE: Postoperative
      change in the eyelid and brow position in downgaze. RESULTS: Of all ptotic
      eyelids, 43% had zero vertical palpebral fissure height in downgaze when the
      brows were relaxed and therefore were functionally blind in the downgaze
      position. After ptosis repair, there was a significant widening of the vertical
      palpebral fissure height in downgaze (P < .001), a significant decrease in
      frontalis muscle use (P < .001), and return of the patients' ability to sustain
      downgaze function. CONCLUSIONS: Measurement of palpebral fissure height in
      downgaze and frontalis muscle use in patients with acquired ptosis identifies
      patients with a functional visual deficit in the downgaze reading position. These
      measurements can be easily performed in the office and may be added to criteria
      for documenting functional impairment from blepharoptosis.

PMID- 7575263
TI  - Infantile uniocular blindness with bilateral nystagmus. A syndrome.
AB  - BACKGROUND: A syndrome has been described in which some patients with uniocular
      infantile blindness have a horizontal nystagmus in their contralateral,
      structurally sound eye. This nystagmus has the characteristics of latent
      nystagmus. This study investigated the hypothesis that this syndrome is present
      when infantile monocular blindness occurs in patients who are genetically
      predisposed to congenital strabismus. In these patients, nystagmus, which would
      be latent, is made manifest by media opacity or suppression acting as an
      occluder. PATIENTS: 1 prospectively studied all patients with this syndrome whom
      I examined between 1982 and 1994. Evaluation included a careful investigation of
      whether there was a family history of congenital strabismus. Three patients
      underwent electro-oculography. RESULTS: The series consisted of 24 patients with
      the syndrome of infantile uniocular blindness with bilateral nystagmus, of whom
      14 (58%) had a family history of congenital strabismus. In a consecutive series
      of 50 patients with monocular congenital blindness caused by opacity of the
      ocular media but not manifesting nystagmus of the contralateral eye, only three
      patients (6%) had a family history of congenital strabismus. This difference was
      statistically significant (P < .01). CONCLUSIONS: It appears likely that the
      syndrome of monocular infantile blindness with bilateral nystagmus represents a
      manifest nystagmus of the latent type in patients who have inherited a genetic
      predisposition for congenital strabismus. In these patients, the monocular
      blindness (opacity of the media or suppression) acts as an occluder, making
      manifest what would have been latent nystagmus.

PMID- 7575264
TI  - Epibulbar complex choristoma associated with nevus sebaceus.
AB  - We encountered an infant with nevus sebaceus of Jadassohn who was born with a
      striking pedunculated mass on the superotemporal aspect of the anterior sclera
      and limbus of the left eye. In addition, two small choroidal colobomas were seen
      in the papillomacular bundle area of the same eye. Histopathologic examination of
      the excised mass revealed a mixture of ectodermal and mesodermal elements,
      including cartilage and bone. These findings led to the rare diagnosis of
      epibulbar complex choristoma.

PMID- 7575265
TI  - Prediction of visual function after cataract surgery. A prospectively validated
      model.
AB  - OBJECTIVE: To develop a model to predict visual functional improvement after
      cataract extraction with intraocular lens implantation based on preoperative
      data. DESIGN: A prospective study with serial evaluations of visual function
      preoperatively and at 3 and 12 months after surgery. SETTING: The General Eye
      Service of the Massachusetts Eye and Ear Infirmary. Boston, Mass, and 33
      ophthalmology practices in Boston. PATIENTS: Patients (N = 426; ages, > or = 65
      years) who were undergoing cataract surgery. METHODS: Twelve-month improvement in
      visual function was measured by using the Activities of Daily Vision Scale
      (ADVS). Ordinal logistic regression was used to identify correlates of improved
      ADVS scores in 281 patients (derivative set). Potential factors included the
      preoperative visual acuity, preoperative ADVS score, four chronic ocular
      diseases, eight medical conditions, and demographic characteristics. Five
      predictors were identified and used to construct a prediction rule. The accuracy
      of the prediction rule was evaluated in an independent group of 145 patients
      (validation set). RESULTS: Postoperatively, 40% of the 281 patients in the
      derivative set had substantial improvement in their ADVS scores, and 53 (19%) had
      some improvement. Predictors of improvement included younger age (P < .001), a
      poorer preoperative ADVS score (P < .001), posterior subcapsular cataract (P =
      .09), and absence of age-related cataract (P = .09), and absence of age-related
      macular degeneration (P = .07) and/or diabetes (P = .006). When applied to the
      independent sample of 145 patients, these five characteristics classified the
      patients into three groups in which the probabilities of substantial improvement
      were 85%, 34%, and 3%, thus verifying the discriminatory power of the prediction
      rule. CONCLUSIONS: Preoperative data can identify patients who are likely to have
      improvements in visual function after cataract surgery. Such findings may be
      useful in the selection of patients for this high-volume procedure.

PMID- 7575266
TI  - Preoperative functional expectations and postoperative outcomes among patients
      undergoing first eye cataract surgery.
AB  - OBJECTIVE: To describe the relationship between patients' preoperative
      expectations regarding the outcome of cataract surgery and actual postoperative
      experience. METHODS: A longitudinal study of 772 patients undergoing first eye
      cataract surgery recruited from 75 ophthalmology practices in three metropolitan
      areas was conducted. Prior to surgery and approximately 4 months after surgery, a
      detailed interview was conducted that included general and vision-specific health
      status measures (including the Visual Function 12-Item Scale [VF-12]), patient
      reported level of trouble and satisfaction with vision, and questions addressing
      patients' preoperative expectations regarding the outcomes of surgery. In
      addition, detailed clinical data were collected preoperatively and
      postoperatively. A total of 552 patients had only single eye cataract surgery by
      4 months postoperatively and are included in this analysis. RESULTS: Patients'
      preoperative expectations regarding the impact of cataract surgery were very high
      and were unrelated to their demographic or ocular characteristics. The
      preoperative VF-12 score, however, was positively correlated with expected
      postoperative VF-12 score (Spearman correlation, .45, P < .001). Only 61% of
      patients achieved or surpassed their expected level of postoperative functioning.
      The difference between expected and actual postoperative VF-12 scores was not
      associated with patients' demographic characteristics or provider-related
      variables. Older patients (> 75 years) and patients with ocular comorbidity had a
      larger difference between expected and actual postoperative functioning than
      younger patients and those without ocular comorbidity. CONCLUSION: Expectations
      regarding visual functioning after cataract surgery are very high, and in most
      cases such expectations are fulfilled. In selected cases, more comprehensive
      counseling may reduce the discrepancy between expectations and actual outcomes of
      cataract surgery.

PMID- 7575268
TI  - Effect of intravitreal dexamethasone in treatment of pneumococcal endophthalmitis
      in rabbits.
AB  - PURPOSE: To investigate whether corticosteroid therapy would decrease the
      inflammation and tissue damage associated with pneumococcal endophthalmitis.
      METHODS: Albino rabbits were injected intravitreally with 1000 live organisms of
      Streptococcus pneumoniae and randomized after 24 hours to treatment with
      intravitreal vancomycin hydrochloride alone (n = 10), combination intravitreal
      vancomycin and intravitreal dexamethasone (n = 10), or no treatment (n = 10).
      After 2 weeks, the eyes were examined clinically and enucleated for
      histopathologic examination. RESULTS: Eyes treated with vancomycin and
      dexamethasone had significantly less intraocular inflammation and more
      preservation of retinal tissue than untreated eyes or eyes treated with
      vancomycin alone (P < .05, Fisher's exact test). Untreated and vancomycin-treated
      eyes were indistinguishable on clinical and histologic examination. Marked
      anterior and posterior segment inflammation with total retinal necrosis was noted
      in eyes from both groups. CONCLUSION: Intravitreal corticosteroid therapy may
      play an important role in minimizing the inflammation and tissue damage
      associated with pneumococcal endophthalmitis.

PMID- 7575267
TI  - Collagen metabolism in human aqueous humor from primary open-angle glaucoma.
      Decreased degradation and increased biosynthesis play a role in its pathogenesis.
AB  - OBJECTIVE: To explore the influence of aqueous humor from patients with glaucoma
      on collagen turnover. METHODS: The aqueous humor of patients with primary open
      angle glaucoma (POAG), chronic angle-closure glaucoma, congenital glaucoma,
      neovascular glaucoma, and senile cataract (control group) was analyzed for its
      capacity to induce fibroblast proliferation, collagen synthesis, collagenolytic
      activity, and production of tissue inhibitor of metalloproteinase-1. All data
      were analyzed using the Mann-Whitney U test. RESULTS: Aqueous humor derived from
      patients with POAG induced a significant decrease of functional collagenase
      activity (mean +/- SE, 9.12 +/- 1.33 microgram of degraded collagen per milligram
      of incubated protein vs 20.94 +/- 4.14 micrograms from the control group, P <
      .05). The enzymatic activity in the other types of glaucoma was similar to that
      of controls. The POAG samples had a significantly higher concentration of tissue
      inhibitor of metalloproteinase-1 (mean +/- SE, 3.11 +/- 0.58 vs 0.91 +/- 0.13
      micrograms/mL from controls; P < .05). The amount of immunoreactive tissue
      inhibitor of metalloproteinase-1 found in the other three groups was not
      significantly different from the control. Aqueous humor stimulated fibroblast
      proliferation in all cases, but significant differences were not observed between
      the POAG samples (mean +/- SE, 20,285 +/- 4642 cpm/mg of incubated protein) and
      the control group samples (26,550 +/- 3688 cpm/mg of incubated protein). Primary
      open-angle glaucoma fluids increased collagen synthesis significantly compared
      with the control group (mean +/- SD, 3352 +/- 630 vs 985 +/- 285, P < .05), and
      the other groups. CONCLUSIONS: An increase of collagen synthesis and a decrease
      of collagen degradation may contribute to an excessive deposit of collagen with
      loss of the trabecular cells during the development of POAG, and aqueous humor
      must be considered as a microenvironment that affects the metabolism or function
      of the trabecular meshwork or both.

PMID- 7575270
TI  - Microcystic adnexal carcinoma of the eyebrow and eyelid.

PMID- 7575269
TI  - Iris flocculi and familial aortic dissection.

PMID- 7575271
TI  - Membrane delaminating wedge.
AB  - Iatrogenic retinal tears may complicate procedures to treat proliferative
      vitreoretinal diseases. To decrease the risk of this complication, we developed a
      new instrument, the membrane delamination wedge, that allows the surgeon to
      separate the proliferative membranes from the retina effectively and safely.

PMID- 7575272
TI  - Where do persons with blindness caused by cataracts in rural areas of India seek
      treatment and why?
AB  - The utilization of eye care facilities by patients with a cataract was evaluated
      among 240 patients selected from eye care camps that were conducted by our
      center. Of the patients, 52.9% had visited previous eye care camps, while 19.2%
      consulted private ophthalmologists. Easy accessibility, reputation of a facility,
      competence of its staff, free service, and nearby facilities were the major
      reasons that were cited by patients for utilization of service facilities.
      Distance, monetary constraints, and a lack of professional trust, escorts, and
      the perception about the seriousness of their ocular condition were the main
      reasons that patients were not motivated to use such service facilities.
      Statistically significant differences were observed when past utilization of eye
      care camps was related to age, marital status, and source of income.

PMID- 7575273
TI  - The stability of facial osteotomies. 2. Mandibular advancement with bicortical
      screw fixation.
AB  - Surgical repositioning of the dento-skeletal components of the lower third of
      face, combined with appropriate orthodontic treatment, can be used to improve
      function and aesthetics. However, the attainment of three-dimensional stability
      following corrective jaw surgery continues to be a major problem in the post
      surgical period. This paper examines the short-term (6 week post-operative) and
      long-term (12 months postoperative) horizontal skeletal stability of bilateral
      sagittal split mandibular advancement in 15 patients. The mean horizontal
      advancement of the mandible was 6.1 mm. Six weeks later, a mean continued forward
      movement of 0.16 mm was identified. The mean relapse at long-term follow-up was
      0.46 mm (7.5%). Results indicate that rigid bicortical screw fixation of
      bilateral sagittal split osteotomies undertaken to correct horizontal lower
      dentofacial deficiency is both statistically and surgically predictable and
      stable when reviewed up to twelve months after surgery.

PMID- 7575274
TI  - The efficacy of Decapinol mouthwash 2 mg/mL in preventing gingivitis.
AB  - In vitro studies and early clinical trials have shown promising results for
      Delmopinol HCl solution as an effective mouth rinse for reducing experimentally
      induced gingivitis in the absence of mechanical plaque control. The efficacy of
      Decapinol mouthwash 2 mg/mL (Delmopinol HCl) in preventing gingivitis in a double
      blind, randomized clinical study with parallel group design was studied. Forty
      seven healthy young adults were randomly assigned to the Delmopinol or placebo
      groups. After an initial period of four weeks of intensive oral hygiene including
      bi-weekly professional cleaning of the teeth and oral hygiene instruction, all
      subjects achieved a low degree of gingivitis or a plaque score close to zero. At
      baseline, Bleeding on Probing, Modified Gingival Index and Plaque Index were
      recorded and the teeth were professionally cleaned. All forms of plaque control
      were then suspended and subjects were supervised in a one-minute rinsing of
      Decapinol mouthwash 2 mg/mL or placebo twice daily. Measurements of efficacy
      variables were then repeated after two and three weeks treatment and adverse
      events were recorded. After the study period of three weeks all previous plaque
      control measures were resumed. At week four, all subjects were reassessed for the
      resolution of gingival inflammation and where residual gingival inflammation
      persisted, appropriate treatment was given. Only mild and short-lasting adverse
      events were noted for the use of Delmopinol in the study period. However, for all
      teeth sites measured, significant differences between Delmopinol and placebo
      groups were found in Bleeding on Probing (p < 0.05) and Plaque Index (p <
      0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575275
TI  - Ectopic supernumerary teeth as a predisposing cause in localized periodontitis.
      Case report.
AB  - Supernumerary teeth are relatively common in the maxillary incisor and molar
      areas. However, bilateral ectopic, fully erupted supernumerary mesiodentes are
      relatively rare. The present case documents a patient with localized
      periodontitis of the maxillary first and second molars associated with
      bilaterally erupted supernumerary teeth located in proximity to the buccal
      embrasure space between the molars. Combined clinical data suggested that these
      ectopic mesiodentes predisposed or contributed to the development of localized
      periodontitis.

PMID- 7575276
TI  - Ectodermal dysplasia. A case with impacted permanent teeth.
AB  - An unusual case of ectodermal dysplasia is presented. Besides the main symptoms
      of ectodermal dysplasia, congenitally missing teeth and the impaction of all the
      other existing permanent teeth make this case interesting.

PMID- 7575277
TI  - Influence of adjacent teeth on impacted third molars in the upper and lower jaws.
AB  - Panoramic radiographs of 1834 patients older than 21 years were evaluated for the
      prevalence of impacted teeth at different ages. The frequency of impacted teeth
      by age was constant, that is, the presence of completely impacted teeth could not
      be related to age. The interrelationship between the angulation of impacted teeth
      and the existence of adjacent teeth was studied in individuals older than 61
      years. The angulation of most of the completely impacted teeth in the upper-third
      molar region was horizontal when adjacent teeth were not present, whereas
      impacted teeth in the upper-third molar region showed vertical angulation when
      adjacent teeth were present, suggesting that vertically impacted teeth may become
      exposed by bone resorption or infection and should be removed. The angulation of
      impacted lower third molars was horizontal irrespective of the presence of
      adjacent teeth. It appears that the interrelationship between the angulation of
      completely impacted teeth and the presence of adjacent teeth is different between
      the upper and lower third molar regions. The angulation of completely impacted
      teeth and the presence of adjacent teeth should be included in those criteria
      which determine whether or not completely impacted teeth should be removed.

PMID- 7575278
TI  - Ectopic third molar in the maxillary sinus. Case report.
AB  - Ectopic eruption of teeth can occur in a wide variety of sites. These include the
      mandibular condyle, coronoid process, palate, nasal cavity and maxillary sinus.
      While this process is unusual, the detection of a third molar in the maxillary
      antrum is extremely rare. A case is presented of ectopic eruption of a third
      molar in the left maxillary sinus of a 35-year-old caucasian male giving rise to
      local morbidity.

PMID- 7575279
TI  - Occlusal reconstruction with implant crown pair prostheses. Case report.
AB  - Occlusal reconstruction of both arches was performed using splinted implant crown
      pairs. Each pair of crowns was luted to parallel implant abutment pairs and these
      were screwed and glued into approximately parallel pairs of implant bodies.
      Paralleling of holes for implant body pairs was performed using a precision
      guiding device.

PMID- 7575280
TI  - The bonding of cold-cured acrylic resin to acrylic denture teeth.
AB  - The necessary improvement of the bonding of denture teeth to the base resin has
      been hampered by inconsistent results and the consequent lack of clear guidance
      as to the best procedure to use. This state of affairs is in part due to poor
      experimental design. The tensile strength of notched planar interfaces between
      acrylic denture tooth material and cold-cured acrylic resin was determined for
      various treatments under a protocol designed to minimize spurious failures. The
      tooth material treatment consisting of grinding and exposure to a methyl
      methacrylate-trichloromethane mixture was, of those treatments, the most reliable
      in that no interfacial failures were observed. Strength was indistinguishable
      from that of both tooth and base acrylic under the same conditions.

PMID- 7575281
TI  - Curriculum development at the University of Sydney.

PMID- 7575282
TI  - The DEET Relative Funding Model and its impact on dental schools.

PMID- 7575283
TI  - The interaction of dental education and regional health care delivery systems.

PMID- 7575284
TI  - Experiences with problem-based learning in oral biology.

PMID- 7575285
TI  - The impact of competencies, mutual recognition and the Australian Dental Council
      on dental education.

PMID- 7575286
TI  - Australian Dental Research Fund Trebitsch Scholarship. Efficacy of antifungal
      prophylaxis in bone marrow transplantation.
AB  - Oral candidal infection is a common problem in bone marrow transplantation. This
      prospective study compared the effectiveness of antifungal prophylaxis with
      topical antifungals (nystatin and amphotericin B suspensions) versus oral
      fluconazole in 196 patients undergoing bone marrow transplantation. Oral
      candidosis occurred frequently in the group receiving topical antifungals
      (61/113, 54%), but was rare in the group receiving fluconazole (6/83, 7%). The
      difference in efficacy between the two groups was highly significant (p <
      0.00001). There was no difference in the incidence of suspected systemic fungal
      infection between the two groups. While nausea was a problem with antifungal
      suspensions, no significant adverse reactions to fluconazole occurred. Because of
      greater efficacy in preventing oral candidosis and better patient tolerance, oral
      fluconazole is preferred to antifungal suspensions for prophylactic use in
      patients undergoing bone marrow transplantation.

PMID- 7575287
TI  - Ethics and competition law.

PMID- 7575288
TI  - Endodontic cellulitis 'flare-up'.

PMID- 7575289
TI  - Occupational health in surgery: risks extend beyond the operating room.
AB  - Surgeons routinely work with potentially infectious materials. The risk of
      acquiring a disease from one percutaneous exposure is 0.3-0.4% for human
      immunodeficiency virus (HIV) 6-30% for hepatitis B virus (HBV) and 2.7-10% for
      hepatitis C virus (HCV). Rates of blood contacts vary but may reach up to 11.9
      per 100 h in the operating room. Residents are at highest risk, and obstetrics
      and gynaecology surgeons suffered the highest rate of exposures (10%) as a group.
      Contributing risk factors include trauma or emergency orthopaedic procedures,
      high patient blood loss, long procedures and holding tissue by hand while
      suturing. However, across occupations, nurses and other health workers experience
      greater risks than surgeons regarding potentially infectious exposures.
      Preventive measures such as the HBV vaccine and protective devices (i.e. self
      capping needles, needle-free i.v. systems and improved barrier materials) have
      reduced the occupational risk of acquiring a blood-borne infection, which allows
      attention to be given to the psychosocial risks which may be more significant,
      yet are often overlooked. Doctors are at greater risk of divorce, alcoholism,
      substance abuse and suicide than are members of comparable professional groups.
      One study found that general surgeons had the highest rates of suicide of all
      doctors. According to family surveys, surgeons tend to be oblivious to the
      effects of work stressors, and may benefit from greater self-awareness; sharing
      of feelings and responsibilities with colleagues, family and patients; being
      willing to delegate work to others; setting work limits; and broadening
      perspectives in their approach to work.

PMID- 7575290
TI  - Prognostic factors and the curability of breast cancer.
AB  - Over the years three different concepts regarding the cure of treated breast
      cancer have emerged. These are clinical cure, personal cure and statistical cure.
      The latter is the most accurate estimate of the curability of a disease which is
      presumed to be fatal unless treated. Statistical cure is the elimination of the
      hazard of death in a treated group compared with an age-matched control
      population. When statistical cure is studied in patients treated for early breast
      cancer, it is clear that breast cancer is an incurable disease. The expected
      gains from the relatively recent introduction of adjuvant therapy are too small
      to alter this concept. The significance of prognostic factors in a disease deemed
      to be incurable therefore requires re-examination. The conventional prognostic
      factors of tumour size, nodal status and a combination of those two in staging
      systems significantly discriminates in terms of survival in the short term.
      However, when the characteristics of long-term survivors are examined, neither
      tumour size nor nodal status discriminates effectively. If this is the case, then
      we need to reconsider novel treatment strategies which have been introduced in
      the hope of increasing the curability of the disease and the selection for those
      treatment strategies of patients using the conventional prognostic factors of
      tumour size or nodal involvement.

PMID- 7575291
TI  - The presentation of breast cancer in an Oriental community.
AB  - A retrospective study was made of the presentation of breast cancer in Chinese
      women who were treated at the University Surgical Unit, Hong Kong, over a 20 year
      period (1971-90). Only 6% of patients presented with tumours less than 2 cm.
      Nearly half the patients presented with advanced disease. There was no tendency
      towards earlier presentation in the latter half of the study period. An increase
      in the number of patients treated for breast cancer was observed; the increase
      being seen mainly in postmenopausal women.

PMID- 7575292
TI  - Renal transplantation in very young children.
AB  - Results of renal transplantation in very young children with end-stage chronic
      renal failure have been poor compared with those in older children and adults.
      Consequently small children either may not be treated or may be placed on chronic
      dialysis programmes. Between 1988 and 1992, six children under the age of 5 years
      received seven renal transplants at the Royal Children's Hospital, Parkville,
      Victoria, Australia; five from live donors and two from cadaver donors. All
      children were treated with peritoneal dialysis before transplantation, and
      immunosuppressed with a standardized regimen of cyclosporine, azathioprine and
      prednisolone. An extraperitoneal incision was used, and the donor renal vessels
      were anastomosed to the lower abdominal aorta and inferior vena cava or the
      common iliac vein. All children received intensive monitoring and fluid
      replacement during the peri-operative period. Patient survival was 100%. One
      cadaver graft failed 1 week after transplantation because of irreversible acute
      rejection. This child subsequently received a successful second transplant. Two
      children developed postoperative urinary fistulae which were treated successfully
      by further operation. Current renal function in all children is excellent. The
      success of this programme has led us to review our attitude towards renal
      transplantation in this age group and to advocate live donor renal
      transplantation as the treatment of choice in very young children with end-stage
      chronic renal failure whenever possible.

PMID- 7575293
TI  - Correlation of the endoscopic appearance with clinical outcome for submucous
      Polytef paste injection in vesico-ureteric reflux.
AB  - The endoscopic injection of Polytef paste is now a well established method of
      treating vesico-ureteric reflux. In this study the video tapes of 64 treatments
      were independently reviewed to assess any predictors of failure. The visual
      appearance of the mound of paste was found to correlate with the clinical
      outcome, except when less than 0.2 mL of paste was used for smaller ureteric
      orifices, or when the ureteric orifice was large enough to admit the 9.3 FG
      cystoscope. In cases with a large ureteric orifice effective treatment was
      achieved without the neat crescent-on-a-mound appearance, provided a larger than
      average volume of paste was used. Meticulous placement of the needle was also
      shown to be important if success was to be ensured.

PMID- 7575294
TI  - Testicular torsion.
AB  - A retrospective review of 80 patients who underwent scrotal exploration for
      presumed testicular torsion is presented. Of these, 67 patients were found to
      have torsion, and the testicular loss rate was 51%. Patients who experienced
      delays in scrotal exploration of more than 24 h from onset of symptoms had a
      testicular loss rate of 71%. These delays arose from both hesitation in seeking
      medical treatment and misdiagnoses. It is emphasized that an acute scrotum in a
      child or in an adolescent should be explored early to exclude torsion.

PMID- 7575295
TI  - Hypospadias: results of treatment in 18 years of paediatric surgical practice.
AB  - This is a review of hypospadias surgery in a provincial surgical practice over 18
      years. A total of 347 boys were seen with hypospadias, of whom 209 were operated
      upon. These operations consisted of 69 Durham Smith de-epithelialized double
      breasting two-stage procedures, 45 meatal advancement and glanuloplasty
      procedures, 27 hemi-circumcisions with or without meatotomy, 24 single stage
      repairs for distal hypospadias without chordee, 23 operations for chordee without
      hypospadias, 15 modified Mathieu single stage procedures and six miscellaneous
      procedures. The complication rate, particularly for fistulae formation in 17%,
      was unacceptably high. Some causes of fistulae were identified; these included
      delayed absorption of chromic catgut sutures and stitch abscess. Stricture
      occurred less frequently, but one case was severe enough to require complete
      revision of the urethroplasty. In early operations a coronal meatus was the norm
      and six patients required advancement procedures.

PMID- 7575296
TI  - Paediatric laryngotracheal reconstruction: Melbourne experience at the Royal
      Children's Hospital.
AB  - A retrospective study was carried out to evaluate the outcome following
      laryngotracheal reconstruction (LTR) performed in 15 children for the treatment
      of severe laryngotracheal stenosis between 1989 and 1993. The age ranged from 18
      months to 19 years with all but one patient being tracheostomy-dependent. The
      tracheostomy tube was successfully removed in 12 children who remain free of
      obstructive symptoms at follow up. One patient was successfully decannulated but
      required repeat tracheostomy 8 months later for intermittent severe
      supraglottic/pharyngeal obstruction. There were two failures, with one of these
      undergoing repeat LTR with successful decannulation. Surgery was complicated in
      one child by aspiration which improved spontaneously. These findings suggest that
      LTR is a safe and effective procedure for the management of severe paediatric
      laryngotracheal stenosis.

PMID- 7575297
TI  - A method for the treatment of ureteric complications following renal
      transplantation.
AB  - Over an 8-year period, 117 renal transplants (97 cadaveric and 20 living related)
      were performed at the Sir Charles Gairdner Hospital, Perth, Western Australia,
      Australia. Ureteric complications following renal transplantation occurred
      following seven transplants (6%). The technique of using a multiply fenestrated
      vesicocutaneous stent/drain to manage this problem is described. This was
      uncomplicated in all cases with the exception of one case in which the
      stent/drain was removed early because of blockage and sepsis, but most
      importantly on no occasion was the graft lost. We therefore recommend this
      technique for the management of this complication, whether early or late. We
      observed a disproportionate number of ureteric complications in living related
      transplants, a feature not described previously.

PMID- 7575299
TI  - Brain abscesses: review of 30 cases treated with surgery.
AB  - Thirty patients with brain abscesses who were treated at the Department of
      Neurosurgery, Tan Tock Seng Hospital, Singapore, during the period July 1989 to
      July 1993, were reviewed. There were seven females and 23 males with mean follow
      up duration of 19 months. The predisposing factors identified were otogenic
      infections in 10 cases (33%), paranasal sinus infection in 2 cases (7%) and
      congenital heart disease in 6 cases (20%). All cases underwent aspiration or
      excision of the abscess. Repeat operations were carried out if the abscess
      reaccumulated. A total of 49 aspirations and 16 excisions were performed. Twenty
      five patients (84%) made a good recovery, three patients (10%) were moderately
      disabled, one patient (3%) was severely disabled and one patient (3%) died. There
      was no postoperative haemorrhage or wound infections. Two patients (7%) developed
      hydrocephalus and three (10%) had seizures postoperatively.

PMID- 7575298
TI  - Percutaneous iodine-125 seed implantation for carcinoma of the prostate.
AB  - This study was performed to assess the early results of treating stages T1-T3
      adenocarcinoma prostate with either Iodine-125 (125I) implant alone (Group 1),
      for smaller more well differentiated cancers, or with low dose external beam
      radiation followed by a 125I boost (XRT + 125I) (Group 2) for larger less well
      differentiated tumours. Eighty-six patients were followed for between 11 and 60
      months with a mean follow up of 26.1. All patients were followed by regular
      prostate specific antigen (PSA) evaluations, and digital rectal examinations
      (DRE). Eighty patients had a follow-up biopsy at 1 year. Prostate specific
      antigen progression-free survival (PSA-PFS) was determined and defined.
      Complications and potency were also assessed. Early results of 125I prostate seed
      implantation are very promising especially for selected cases of localized
      carcinoma.

PMID- 7575300
TI  - Effects of vesicocolic anastomosis on the proliferation of colonic mucosa in a
      rat model.
AB  - The effects of diverting the urinary stream into a defunctioned segment of the
      distal colon has been studied in a rat model. Distal rat colon was defunctioned
      using the Hartmann's procedure and a vesicocolic anastomosis was performed 14
      days later. The distal colon was harvested after 10 days following the
      administration of a vinblastine mitotic block either 1 or 3 h before death. Both
      the mean crypt cell proliferation and the crypt length were increased
      significantly in the colonic mucosa exposed to urine when compared with the
      control defunctioned colon or to the functional unexposed proximal colon. An
      active fraction was obtained from human urine by elution from a diethylaminoethyl
      sepharose column using 1 mol/L NaCl. This fraction was administered
      intraluminally to defunctioned rat colons using Alzet minosmotic pumps. In these
      animals the crypt cell production rate was significantly increased compared with
      the control animals. Although the crypt length did not increase significantly in
      these animals the atrophy normally seen in defunctioned colonic mucosa did not
      occur. The identity of the active molecule in this urine fraction is still being
      determined.

PMID- 7575301
TI  - A double lumen suprapubic urodynamic catheter.
AB  - A 7.5 FG double lumen suprapubic urodynamic catheter has been developed to avoid
      the effects of urethral catheterization and provide reliable continuous pressure
      monitoring. The device is an adapted central venous catheter which is easily
      introduced through a peel-away sheath, after the insertion of a guide wire.

PMID- 7575302
TI  - Recent advances in pain management.
AB  - Over the last 20 years there has been an upsurge of interest in the basic
      mechanisms of pain. The findings that have arisen as a result of this interest
      have flowed through to the clinical area and have seen applications in a variety
      of settings. Identification of receptors and processes that are involved in the
      transmission of pain has led to the use of new agents in pain management. New
      techniques have provided new and more effective approaches in managing pain.
      These include the use of pre-emptive analgesia, postoperative pain management
      with patient controlled analgesia and use of techniques such as intrathecal drug
      administration and epidural spinal cord stimulation. This review presents some of
      the findings from basic research which have led to these developments, in
      particular those that relate to the changes that occur following inflammation and
      nerve injury, and the implications that these findings have had on pain
      management.

PMID- 7575303
TI  - Adult hepatoblastoma: case report and review of the literature.
AB  - We report a case of hepatoblastoma in a 24-year-old woman. The tumour was removed
      by an extended right lobectomy after transcatheter hepatic arterial embolization.
      A survey of the literature revealed 31 cases of adult hepatoblastoma. According
      to these reports there are no characteristic clinical features of the tumour,
      making a correct diagnosis before surgery or autopsy extremely difficult.
      Complete removal of the tumour is the only treatment which is potentially
      curative provided that lesion is confined within the liver capsule.

PMID- 7575304
TI  - Hernia uteri (correction of: uterus) inguinale associated with unilateral renal
      agenesis.
AB  - We report a patient with a rudimentary uterine horn, fallopian tube and ovary in
      an inguinal hernia. Associated with this abnormality the patient had ipsilateral
      renal agenesis and a unicornuate uterus.

PMID- 7575305
TI  - Right aortic arch with aberrant left subclavian artery: aneurysmal dilatation
      causing symptomatic compression of the right main bronchus in an adult.
AB  - A 60-year-old woman presented with a cough, nocturnal stridor and dysphagia.
      Bronchoscopy showed tight compression of the right main bronchus. Digital
      subtraction angiography (DSA) and a computed tomographic (CT) scan showed the
      presence of a right-sided aortic arch with aberrant left subclavian artery. The
      distal right arch and proximal right-sided descending thoracic aorta were
      aneurysmal and were responsible for this compression. Surgical relief was
      accomplished by dividing the aberrant left subclavian artery and replacing the
      aneurysm with a vascular graft.

PMID- 7575306
TI  - Nimodipine levels in breast milk.
AB  - Nimodipine is an established drug in the treatment of symptomatic subarachnoid
      haemorrhage. However no data exist as to whether the drug has been detected in
      breast milk. This paper reports on a lactating patient who was commenced on
      nimodipine for a symptomatic arterial spasm after aneurysm surgery. Assays
      demonstrated that nimodipine was detected in the breast milk in relatively
      similar concentrations to plasma.

PMID- 7575307
TI  - A rare complication of pectoralis major rupture.
AB  - Pectoralis major rupture is an uncommon injury. Only 85 cases have been reported
      in the literature. Rupture may be partial or complete. The treatment of partial
      rupture is conservative, whereas in cases of total rupture surgical repair is
      advocated, particularly in young active patients. Complications are few. We
      describe a case of infection of the haematoma following a partial rupture. To the
      best of our knowledge it is the first case to be reported in the English
      literature.

PMID- 7575308
TI  - Interpersonal relations during simulated space missions.
AB  - The present article derives from two isolation studies performed for the European
      Space Agency (ESA) as simulations of space travels, lasting for 4 and 9 weeks.
      The aim was to study how interpersonal relations were affected by time, and how
      individual characteristics related to conflicts and tension among crewmembers. A
      broad battery of methods was used, including video-recording, peer-ratings and
      self-reports. In both studies, group-functioning declined in the middle of the
      isolation and towards the end of the stay. Dominance and task motivation seemed
      to be important characteristics for compatibility between crewmembers, and
      negative relations established early in the isolation remained stable over time.
      These findings have implications for composition, training, and support of crews
      for extended spaceflights.

PMID- 7575309
TI  - Effect of sickness severity on habituation to repeated motion challenges in
      aircrew referred for airsickness treatment.
AB  - The aim of this study was to determine whether varying the predetermined malaise
      level at which provocative motion challenges were stopped would affect the
      habituation rate. At the rate of 2 per day, 21 motion challenges were delivered,
      stopping either at initial symptoms or at moderate nausea, on a cross-over design
      randomized between subjects (n = 20). The cross-coupled motion challenge had an
      incrementing profile of rotational velocity from 2-90 degrees.s-1 in steps of 2
      degrees.s-1 every 30 s, with 8 head movements per 30 s, of approximately 45
      degrees. The number of head movements tolerated before the onset of nausea
      increased over the 21 challenges, but the effects of the treatment variation on
      habituation were not significant. The number of motion challenges, rather than
      the severity of malaise level achieved, was the more important factor determining
      habituation.

PMID- 7575310
TI  - P6 acupressure reduces symptoms of vection-induced motion sickness.
AB  - PURPOSE: The purpose of the study was to examine the effectiveness of P6
      acupressure on nausea associated with visually-induced motion sickness. METHOD:
      There were 64 subjects randomly divided into 4 groups: P6 acupressure, dummy
      point acupressure, sham P6 acupressure, and control. Each subject sat in an
      optokinetic drum for a 12-min baseline and 12-min drum rotation period. Subjects'
      electrogastrograms (EGG's) and subjective symptoms of motion sickness were
      obtained. RESULTS: The results indicated that the subjects in the P6 acupressure
      group reported significantly less nausea [F(3,60) = 8.16, p < 0.0001] during drum
      rotation period than those in the dummy-point acupressure, sham acupressure, and
      control groups. The scores for symptoms of motion sickness of the P6 acupressure
      group were significantly lower than those in the sham acupressure and control
      groups [F(3,60) = 3.49, p < 0.02]. Also, the subjects in the P6 acupressure group
      showed significantly less abnormal gastric myoelectric activity, tachyarrhythmia,
      than those in the sham acupressure and control groups [F(3,60) = 2.78, p < 0.04].
      However, the subjects in the dummy-point acupressure group did not report
      significantly fewer symptoms and show less tachyarrhythmia than those in the sham
      acupressure and control groups. CONCLUSION: We conclude that P6 acupressure
      reduces the severity of symptoms of visually-induced motion sickness and gastric
      tachyarrhythmia.

PMID- 7575311
TI  - Effect of alcohol on the threshold for detecting angular acceleration.
AB  - We investigated the effects of a low blood alcohol level (mean BAC = 0.037%) on
      subjects' ability to detect acceleration and deceleration of angular motion. The
      angular motion thresholds of six alcohol and six placebo subjects, all of whom
      had private pilot certificates, were tested under double-blind conditions in an
      enclosed simulator apparatus prior to drinking, after drinking, and at a time
      when the BAC's of alcohol subjects had reached zero. Mean threshold values for
      the three threshold determination sessions were 0.282, 0.376, and 0.343 degrees.s
      2 respectively for the alcohol subjects, and 0.263, 0.262, and 0.262 degrees.s-2
      for placebo subjects. A significant alcohol x test-session interaction (p <
      0.005) reflected the elevated thresholds shown by all alcohol subjects after
      consuming alcohol (p < 0.001). Of the six alcohol subjects, four continued to
      have elevated thresholds after their BAC's reached zero (p < 0.001). Alcohol and
      placebo subjects showed similar performance on the ancillary tasks of maintaining
      altitude and reporting a specified number when it appeared on a digital display.
      Both groups also reported that they had experienced similar levels of discomfort
      symptoms before and after drinking. The results indicate that a pilot's ability
      to detect angular motion can be compromised by low BAC levels, and this effect
      may continue for some pilots after their BAC reaches zero.

PMID- 7575312
TI  - Long term stability of somatosensory evoked potentials and the effects of
      microgravity.
AB  - BACKGROUND: Exposure to microgravity causes a height increase of up to 70 mm that
      places traction on the spine and may possibly lead to spinal cord dysfunction.
      Somatosensory evoked potentials (SSEP) have been widely used to monitor spinal
      cord function. This study was carried out to determine the long-term stability of
      the latency of SSEP's in individual subjects and the feasibility of recording
      SSEP's in a microgravity environment. METHODS: Baseline values and variability of
      the latency of the cortical evoked potentials were established in seven subjects
      over periods of 1-2.5 years. These values were then compared with measurements
      made in six of the subjects during periods of microgravity on a KC-135 aircraft.
      The latency of the cortical potentials was also measured in the evening and in
      the morning before rising in a separate group of seven subjects, to determine
      whether there was any diurnal variation. RESULTS: The mean coefficient of
      variance of the latency of the SSEP was approximately 1.5% of the latency, and
      there were no changes in the latency over the period studied. There was no
      evidence of diurnal variation in the latency of the cortical SSEP. Satisfactory
      recordings of the SSEP were obtained in five of six subjects tested in
      microgravity. In three of these five subjects there was a significant decrease in
      the latency of the cortical SSEP in microgravity. CONCLUSIONS: In individual
      subjects the latency of the cortical SSEP varies within very small limits (1.5%)
      over 1-2.5 years. The results demonstrate the feasibility of recording SSEP's in
      the microgravity state. They show that relatively small changes (2-3 ms) in the
      latency of the SSEP can be detected when prior baseline values are established
      for each subject. The reason for the decrease in latency of the cortical SSEP in
      some subjects on the KC-135 is not known.

PMID- 7575313
TI  - A comparison of visual and auditory reaction time and P300 latency thresholds to
      acute hypoxia.
AB  - To investigate the influence of stimulus modality on the slowing produced by
      hypoxia, thresholds were estimated using reaction time (RT) and the event-related
      brain potential P300. Six trained subjects responded to oddball light flashes or
      tone pips while breathing low-oxygen mixtures that were manipulated to produce
      arterial blood oxygen saturations (SaO2) ranging from 77-86%. Both RT and P300
      were slowed in a dose-dependent manner. The threshold for slowing was independent
      of stimulus modality for both measures, and estimated to be in the range 81-82%
      SaO2. P300 amplitude dissociated from the response time measures by exhibiting an
      inverted-U dose-response function. We draw three conclusions from these results:
      a) the failure to observe a higher visual threshold for the response time
      measures is inconsistent with the traditional belief that audition is relatively
      insensitive to hypoxia; b) the equal sensitivity of P300 latency and RT to
      hypoxia implicates stimulus evaluation processes in slowing; and c) P300
      amplitude may reflect the activity of physiological compensatory mechanisms to
      hypoxia.

PMID- 7575314
TI  - Effect of triazolam on responses to a cold-water immersion in humans.
AB  - Managing alertness of soldiers during sustained operations is a source of serious
      concern for military unit commanders. A frequently employed strategy is to induce
      sleep before an operation, especially operations requiring prolonged travel.
      Sleep-inducing drugs could have an action on thermoregulation through their
      effect on alertness and a possible direct effect on the brain. The goal of this
      study was therefore to evaluate the effect of a commonly prescribed triazolam
      (Halcion) on thermoregulatory responses to cold-water immersion. Eight subjects
      were immersed twice in 18 degrees C water for up to 90 min in the morning; once
      after ingesting 0.25 mg triazolam (TRZ) the prior evening, and again after
      placebo (PLB) treatment. There were no significant differences between trials for
      mean duration of the immersion, the change in rectal temperature and mean skin
      temperature. Total metabolic heat production was similar for both conditions: 767
      +/- 107 vs. 781 +/- 105 kj.m-2 for TRZ and PLB, respectively. The results should
      be considered in light of a large variation among the subjects in sensitivity to
      TRZ, which was unrelated to biometrical characteristics such as surface area-to
      mass ratio, lean body mass, % body fat, and physical fitness. Although not
      statistically significant, there was a trend for a smaller increase in plasma
      free fatty acid and glycerol concentrations after water immersion with TRZ. The
      results suggest that the ingestion of a single dose of triazolam 11 h prior to a
      cold-water immersion is not likely to accelerate the rate of onset of
      hypothermia. Individual sensitivity, however, may predispose some sensitive
      subjects to negative effects in this regard.

PMID- 7575315
TI  - Cardiovascular deconditioning occurs during a 7-day saturation dive at 31 ATA.
AB  - Cardiovascular deconditioning (CD) has been reported to occur within 24-48 h of
      exposure to 4, 11, or 31 ATA environment and following decompression to sea level
      pressure. The CD was indicated by orthostatic intolerance, exaggerated
      cardiovascular responses to a passive tilt, an elevated resting heart rate and a
      reduced stroke volume postdive. In this dive, one of the New Seatopia series, we
      used a non-syncope criterion, the cardiovascular index of deconditioning (CID;
      Bungo MW, Johnson PJ Jr. Aviat Space Environ Med 1983; 54:1001), to evaluate CD
      in 3 male subjects. The CID sums the changes in heart rate and blood pressure in
      response to orthostatic stress. An elevated CID indicates CD. We used a passive
      70 degrees head up tilt as the orthostatic stress. The CID was measured before
      and after a bout of underwater exercise at predive, during the early, mid, and
      late exposure of the 7-d 31 ATA, and after the dive. The CID and circulatory
      responses to tilt were similar before and after the exercise. The CID increased
      (p < 0.05) from the predive value of 20 +/- 1.6 to 25 +/- 0.9 on the 2nd day, to
      25 +/- 0.8 on the 4th day at 31 ATA, indicating the presence of CD at the early
      and mid periods of hyperbaric exposure. However, CID was indifferent (18 +/- 0.6)
      from the predive on the 7th day at 31 ATA. The increased CID corresponded to
      decreases in plasma volume during the early and mid periods of 31 ATA
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575316
TI  - Cavitation/boundary effects in a simple head impact model.
AB  - An experimental and numerical analysis of the impact response of a simple model
      of the human head is presented. A water-filled 14-cm diameter cylinder was struck
      by a 10 kg free flying mass. Rigid-body acceleration-time-history and the
      pressure at the fluid-cylinder interface were monitored during the impact event.
      Comparisons between the experimental results and the results of a computational
      model were made. The computational model used is a two-dimensional finite
      difference code simulating the physical experiment. The code incorporates a thin
      layer of air and the potential for vaporization along the inside of the cylinder.
      The study indicates that during a severe impact to the human head, the stresses
      generated within the brain can result in cavitation on the far side of impact
      followed by a sudden cavity collapse which can be quite violent. The study
      identifies how a skull-brain interface and cavitation can potentially affect the
      internal pressure response of the brain when subjected to a sudden impact.

PMID- 7575317
TI  - Psychological first-aid: a practical aide-memoire.
AB  - Despite advances made in recent years in medical first aid, psychiatric
      intervention, survival training and equipment design, many people still perish
      quickly during and immediately following a disastrous event. In this study,
      individuals and groups of survivors of life-threatening events were debriefed and
      the behavior of those who coped well during such a threat to life were compared
      with those who did not. The behaviors of those who coped well were distilled into
      a set of principles for psychological first aid; that is, a series of simple
      actions for use within a disaster which serves to recover victims to functional
      behavior as quickly as possible, thus increasing their chance for survival. These
      principles of psychological first aid have recently been introduced into basic
      first aid and survival training courses for both military and civilian units.

PMID- 7575318
TI  - Greyout, blackout, and G-loss of consciousness in the Brazilian Air Force: a 1991
      92 survey.
AB  - A national survey has been performed with high and medium performance aircraft
      pilots on the incidence of symptoms due to +Gz acceleration, in order to make up
      a human centrifuge physiological training profile directed to the needs of the
      Brazilian Air Force pilots. Anonymous questionnaires were sent to Flight
      Squadrons of F-5, AMX, Mirage F-103, Xavante AT-26, and Tucano T-27. They
      consisted of inquiries about the occurrence of visual symptoms and/or loss of
      consciousness during +Gz (G-LOC) maneuvers, and post-G-LOC symptoms. Some 193
      pilots answered the questionnaire: 23 (11.92%) reported greyout and/or loss of
      peripheral vision; 40 (20.72%) reported blackout; 20 (10.36%) reported G-LOC.
      Those who reported LOC also reported post-G-LOC symptoms (100%), 16 (80%) being
      gradual and 4 (20%) instantaneous. Incidence of G-LOC did not depend upon the
      type of aircraft flown (p > 0.05). Considering the pilots who reported G-LOC, 80%
      were preceded by blackout, which could allow them to relieve +Gz load before they
      would reach their endpoint for the occurrence of G-LOC. For these reasons we
      recommend intensive human centrifuge training periodically, similar to the
      hypoxia-recognition test in the hypobaric chamber, not only for high performance
      aircraft pilots but for any pilot who can perform aerobatics (thus exposing
      himself to the adverse effects of "pulling G"). This will allow each pilot to
      recognize his consciousness endpoint when undergoing +Gz maneuvers, in a
      controlled and safe environment.

PMID- 7575319
TI  - Cold water immersion simulations using the Wissler Texas Thermal Model:
      validation and sensitivity analysis.
AB  - BACKGROUND: Wissler's Texas Thermal Model (TM) has been used to simulate the
      effects of thermal stresses on individuals under a variety of conditions. As part
      of a U.S. Navy effort to develop integrated protection garments, TM was modified
      to predict tolerance to cold water immersion (CWI) with garments with clo values
      less than 0.1 (15). METHODS: With these modifications, TM predictions were
      validated using experimental data obtained from 39 males and females during anti
      exposure suit CWI assessments. Data analyses were based on changes in rectal
      (Tre) and various skin temperatures (Tsk). A sensitivity analysis was also
      performed to determine which TM parameters were most affected during simulated
      CWI. The condition tested was head-out immersion in 4.4 degrees C water by a 72.6
      kg man (10 mm mean skinfold thickness). RESULTS: For most of the subject pool,
      the estimated change in Tre, chest, thigh, calf, and arm temperatures were not
      statistically different from experimental values. However, TM predictions were
      less accurate with respect to female responses. Based on thermal end points, TM
      predictions indicated that the following body segments were most sensitive to
      changes in insulation level (ordered from most to least important): chest and
      abdomen, leg, head, and arm. The physical parameters mean skinfold thickness,
      basal metabolic rate, body weight, and exercise metabolic rate had the most
      impact on TM predictions. CONCLUSIONS: The relative benefit of increased
      insulation on individual body segments was identified to aid garment design.
      Further, the relative importance of model physical parameters was identified so
      that judicious initial conditions could be selected to ensure that only garment
      design changes would be reflected in model predictions.

PMID- 7575320
TI  - Deaths and injuries as a result of lightning strikes to aircraft.
AB  - Aircraft are at risk of being struck by lightning or triggering lightning as they
      fly through clouds. Commercial and private airplanes have been struck, with
      resultant deaths and injuries to passengers and crew. We were interested in
      learning how large a problem existed to the American public from lightning
      strikes to airplanes. We analyzed data from the National Transportation Safety
      Board (NTSB) on lightning-related accidents in the United States from 1963-89.
      NTSB recorded 40 lightning-related aircraft accidents. There were 10 commercial
      airplane accidents reported, 4 of which were associated with 260 fatalities and
      28 serious injuries. There were 30 private aircraft accidents that accounted for
      30 fatalities and 46 serious injuries. While lightning remains a potential risk
      to aircraft passengers and crew, modern airplanes are better equipped to lessen
      the dangers of accidents due to lightning.

PMID- 7575321
TI  - Excimer laser photorefractive keratectomy (PRK) for myopia--present status:
      aerospace considerations.
AB  - Excimer laser photorefractive keratectomy (PRK) to reduce myopia has been studied
      the past 3 yrs at multicenters authorized by the FDA. The excimer laser ablates
      the central cornea to a new calculated power. A review of the cases reported in
      the literature reveals the following information: Corneal scarring may be
      reflected in the loss of best-corrected vision. Regression of the refractive
      effect is a complication. Predictability was the percentage of eyes obtaining
      20/40 or better vision; this varied from 62.5-91%. Conversely, 9.0-37.5% were
      20/50 or worse. Low to moderate myopes had better visual success. Accuracy was
      the refractive correction within +/- 1.00 D (spherical equivalent); this varied
      between 64.7-93%. The higher percentages were with low to moderate degrees of
      myopia. Loss of best corrected vision was due to scarring and haze, and occurred
      more frequently with high myopia and deeper ablations. Patient satisfaction after
      2 yrs was reported as 82.6-90%; 17.4% were not satisfied. ADVANTAGES: a) PRK
      effectively and safely corrected myopia and myopic astigmatism; b) there was no
      diurnal variation of refraction or vision; c) vision remained fairly stable with
      some regression up to 24 mo and; d) accuracy of correction to +/- 1.00 D was
      fair. Disadvantages: a) post-operative scarring and haze was present after 6 mo
      to 2 yrs of follow-up in some cases. Scarring was less with low myopia and worse
      with high myopia; b) regression of correction and blur; and c) poor night vision,
      halos, and glare sensitivity occurred after pupil dilation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7575322
TI  - Alcohol & tobacco: some good news & some bad news.

PMID- 7575323
TI  - The USAF ambulance system.

PMID- 7575324
TI  - Spatial disorientation.

PMID- 7575325
TI  - 1995 award winners of the Aerospace Medical Association.

PMID- 7575326
TI  - John Paul Stapp Award--1995 presented to James W. Brinkley.

PMID- 7575327
TI  - G protein-coupled receptor structure and function: the impact of disease-causing
      mutations.
AB  - Just as the discovery of 'inborn errors of metabolism' in humans contributed to
      our basic understanding of normal enzymatic pathways, so can genetic defects in
      signal transduction help to elucidate the functions normally subserved by
      different GPCR pathways. Identification and characterization of naturally
      occurring GPCR mutations not only has inherent value in understanding the
      molecular basis of disease, but can also accelerate progress in understanding the
      fundamental mechanisms involved in GPCR synthesis, transport to the membrane,
      ligand binding, activation and deactivation.

PMID- 7575328
TI  - The molecular pathology of pituitary hormone deficiency and resistance.
AB  - In this chapter, we have reviewed the fast-moving area of the molecular pathology
      of pituitary hormone deficiencies and resistance. Examples have been described
      affecting all levels of pituitary function, i.e. the releasing hormone, its
      receptor, the pituitary hormone and its receptor, and the development of the
      pituitary gland. Other examples in these genes, and in those in which no mutation
      has yet been found, will undoubtedly be discovered in the next few years,
      throwing light on the structural basis of the gene product's function and
      allowing a greater understanding of endocrine physiology and pathophysiology. The
      main reason for this rapid progress in knowledge is the recent technological
      advances in mutation detection, which bring this activity within the grasp of the
      majority of reasonably equipped laboratories. Technological advancement, however
      is not all that it takes to carry out this work. The conditions caused by genetic
      damage such as we have described are rare, and there is clearly a requirement for
      great awareness on the part of the clinical endocrinologist. Patients in whom it
      is suspected that mutations such as these may occur require careful clinical and
      biochemical work-up. Indeed, in many instances, careful thought has to go into
      deciding what the phenotype of a particular mutation might be. Thus, the
      requirement for close collaboration between clinical and molecular
      endocrinologists has to be the important message for the future in this area of
      research.

PMID- 7575329
TI  - A molecular approach to the pathophysiology of the X chromosome-linked Kallmann's
      syndrome.
AB  - The human KAL gene is responsible for the X chromosome-linked Kallmann's
      syndrome, which consists of an association between hypogonadotropic hypogonadism
      and anosmia (or hyposmia). Additional symptoms are occasionally observed. The
      olfactory defect is associated with hypoplasia of the olfactory bulbs and tracts.
      The hypogonadism may be due to a defect in the embryonic migratory process of
      GnRH-synthesizing neurones from the olfactory pits up to the brain. The human and
      chicken KAL genes have been isolated. From the amino acid sequences deduced, it
      has been postulated that the KAL protein is an extracellular matrix component,
      with putative antiprotease activity and adhesion function. Various point
      mutations and, in a few cases, deletions of KAL have been detected in patients.
      By in situ hybridization, KAL expression has been studied during embryonic
      development in the chick. From embryonic day 2 (ED2) to ED8, the KAL gene is
      expressed in various endodermal, mesodermal and ectodermal derivatives, whereas
      the expression from ED8 is almost entirely restricted to definite neuronal
      populations in the central nervous system, most of which still express the gene
      after hatching. According to such a spatiotemporal pattern of expression, we
      suggest that the KAL gene is involved both in morphogenetic events and in late
      neuronal differentiation and/or neuronal trophicity. With respect to the
      olfactory system, the KAL gene is expressed in the mitral cells of the olfactory
      bulbs from ED8 onwards. In contrast, no expression of the KAL gene is detected at
      any stage in either the embryonic olfactory epithelium or the surrounding nasal
      mesenchyme. Therefore, assuming that similar conditions are found in the human
      embryo, we suggest that the olfactory anomaly in X-linked Kallmann's syndrome
      results from a central target cell defect. Current hypotheses regarding the
      pathophysiology of the GnRH deficiency are also discussed. In situ hybridization
      experiments in the human embryo, as well as characterization of the KAL protein,
      are in progress.

PMID- 7575330
TI  - Diabetes insipidus.
AB  - The advances in our understanding of the pathophysiology of defects in the
      antidiuretic hormone, the V2 receptor and the water channel, owing to mutations
      in the prepro-AVP-NPII, AVPR2 and AQP2 genes respectively, is providing insight
      into inherited diabetes insipidus as well as the more numerous sporadic cases.
      Further structure-function analyses of these mutated genes will increase our
      understanding of normal vasopressin-regulated water transport across the kidney
      epithelium at the molecular level.

PMID- 7575331
TI  - Genetic disorders of steroid hormone synthesis and metabolism.

PMID- 7575332
TI  - Disorders of sexual development.
AB  - Over the past 6 years, the structures of four key genes involved in sexual
      differentiation have been identified (see Figure 2). Mutations within these genes
      have been demonstrated to cause a significant percentage of the disorders of
      sexual differentiation described in this chapter. It should be noted, however,
      that there are significant numbers of patients with these disorders in whom no
      mutation in any of these genes has yet been characterized. It is probable that
      further genes involved in sexual differentiation will be identified and shown to
      be the cause of a number of these diseases.

PMID- 7575333
TI  - Molecular genetics of disorders of calcium homeostasis.

PMID- 7575334
TI  - RET proto-oncogene mutations in multiple endocrine neoplasia type 2 and medullary
      thyroid carcinoma.
AB  - The identification of RET proto-oncogene mutations in patients with MEN2 2 years
      ago was a watershed event in the management of this genetic cancer syndrome. The
      identification of a finite number of mutations that together causes more than 95%
      of hereditary and 15-25% of sporadic MTC has made it possible to develop simple
      and definitive tests to screen individuals at risk for this tumour syndrome. The
      impact of this technology is enormous. It is now possible to reassure 50% of
      family members at risk that they, and their children, do not have to worry about
      developing MTC. In the other 50% who are gene carriers, it is now possible to
      approach clinical management with greater certainty and plot strategies that are
      likely to result in a greater percentage of curative therapy. It seems likely
      that this technology will also have an impact on the management of sporadic MTC,
      although it is still too early to define a specific role for mutational analysis
      in these patients, except to exclude hereditary disease. The identification of
      specific mutations causative for MTC makes it possible to conceive future
      strategies for the treatment or prevention of MTC and to further extend the
      impact of these exciting findings.

PMID- 7575335
TI  - Molecular genetics of diabetes mellitus.
AB  - As a result of advances in technology, genome searches have been carried out for
      susceptibility genes for type 1 diabetes in humans and in the NOD mouse. These
      have shown that, in the NOD mouse, diabetes susceptibility is under the control
      of at least ten separate chromosomal loci. In the human, in addition to HLA and
      INS, two new susceptibility genes have been localized, IDDM4 on chromosome 11q
      and IDDM5 on 6q, demonstrating the polygenic nature of type 1 diabetes and the
      role of HLA as the major locus. Candidate genes at these loci are the subject of
      current investigation. Genetic and immunological markers of disease may be of
      value in screening the general population for individuals at risk of developing
      type 1 diabetes. The predictive power of different screening strategies should be
      tested in order to work out the potential value to the general population of
      preventive therapies that are now undergoing clinical trials in high risk 'pre
      diabetics'. Type 2 diabetes is genetically heterogeneous, and, since 1992, two
      distinct genetic subtypes have been identified. The first is defined by mutations
      in the GCK gene, which cause up to 60% of cases of MODY. The second, designated
      MIDD (maternally inherited diabetes and deafness), is defined by mutation in the
      mitochondrial gene for tRNA(Leu(UUR)). MIDD patients are less obese than is usual
      for typical type 2 diabetes, may present in early adult life or occasionally in
      childhood and may have been diagnosed as having autoimmune type 1 diabetes, type
      2 diabetes or MODY. Typically, patients with MIDD require insulin earlier than do
      type 2 diabetics without mitochondrial mutations. Genetically complex diseases,
      such as diabetes, hypertension, cancer and coronary heart disease, are common in
      most populations. The approaches to the genetic analysis of diabetes outlined in
      this review are likely to be useful to the genetic analysis of many of these
      disorders. Progress in this area will have important implications for public
      health strategies in the next decade and beyond.

PMID- 7575336
TI  - Molecular basis of human hypertension: the role of angiotensin.
AB  - On the basis of recent advances in molecular biology and statistical genetics, it
      has become possible to search for chromosome regions that contain genes
      predisposing to hypertension and to directly link specific mutations on candidate
      genes to hypertension. As the human genome has been extensively mapped, highly
      informative, polymorphic markers are available, which can be used to detect genes
      in their proximity with 'hypertensinogenic' alleles. Some of these markers have
      been shown to be tightly linked to the genes of the renin-angiotensin system.
      Furthermore, the coding and regulatory regions of the genes encoding for renin,
      ACE, angiotensinogen and the AT1 receptor have been partially characterized. This
      provides a basis for further definition of specific polymorphisms within these
      genes that are of functional importance and that can be used to examine their
      contribution to the inheritance of primary hypertension. The first studies of
      these links have already emerged and have been reviewed in this article. Several
      problems arise in performing such linkage studies in human primary hypertension,
      however. It is difficult to define the genetic background of heterogeneous,
      multigenetic and multifactorial diseases such as human hypertension. Extensive
      studies of population genetics, including the analysis of large numbers of
      generations and controlled breeding experiments, cannot be performed, for obvious
      reasons. Blood pressure is not a convenient study trait, because it exhibits
      great intraindividual variance and also because of the relatively low reliability
      of just a few indirect measurements obtained under loosely controlled
      environmental conditions. Twenty-four-hour ambulatory blood pressure measurements
      may improve such investigations in the near future. Ravogli et al (1990) reported
      that the 24-hour ambulatory systolic blood pressure is higher in normotensive
      subjects of hypertensive parents than in normotensive subjects of normotensive
      parents--a finding that had not been previously reported using the conventional
      method of measurement. Hypertension as a trait per se is also problematic: its
      classification (above 140/90 mmHg) is purely artefactual, and its aetiology is
      highly heterogeneous. Thus, we have to keep in mind that even strong gene
      effects, if present in only a small subgroup of hypertensives, may not be
      detected in these studies. Attempts are being made to strengthen the analysis by
      characterizing physiologically distinct subgroups. In addition, the investigation
      of intermediate phenotypes, such as plasma parameters, which are more reliable
      and less subject to variations, may be helpful.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7575337
TI  - Dietary energy intake, energy expenditure and activity pattern among selected
      rural and urban poor in Bangladesh.
AB  - Rural-urban and seasonal differences in energy balance were studied among
      selected free living subjects, chosen from the poor population groups in
      Bangladesh. Individual dietary energy intakes were estimated by a combination of
      24 hours recall and weighing method. Time allocation to various occupational and
      non-occupational activities were recorded by observation and questioning, and
      energy expenditures were calculated by using FAO/WHO/UNU guidelines. The male
      working adults in both the population groups studied were found to be in negative
      energy balance in both the seasons observed. In Jan-Feb when employment
      opportunities for the rural poor were few all age and sex groups were in negative
      energy balance, and when employment opportunities improved during May-June the
      situation reversed except for the male working adults. In urban areas, on the
      other hand, all age and sex groups, except the male working adults were in
      positive energy balance in both the seasons. Rural children under 10 years, had
      significantly higher energy expenditure (P < 0.023) than their urban
      counterparts. Seasonal difference in energy expenditure among the rural male
      adults is quite high. In the urban group there was no such seasonal difference.
      Apparently very high rural-urban difference in energy expenditure of the male
      adults (18-30 y) in season 1 may be attributed to very high energy demanding
      activities in which the observed subjects in rural areas were engaged during this
      season. Compared to their urban counterparts rural male adults (18-30 yrs.) were
      found to be devoted significantly higher time in occupational and heavy household
      activities.

PMID- 7575338
TI  - Development and evaluation of co-agglutination test to detect rotavirus antigens
      in stools of patients with diarrhoea.
AB  - Rotavirus is the most common cause of acute diarrhoea in infants and children in
      both the developed and developing countries including Bangladesh. Information
      about rotavirus diarrhoea in Bangladesh is insufficient primarily due to the lack
      of diagnostic facilities due to the high cost of reagents and equipment and lack
      of skilled personnel. A simple, suitable and less costly technique of co
      agglutination test using protein-A secreting staphylococci was developed and
      evaluated against a commercially available ELISA kit to detect rotavirus antigen
      in stools of patients with diarrhoea. Staphylococcus cowan strain 1 was grown and
      coated with rabbit antisera raised against RV5 and SA11 rotavirus strains. The
      antibody-coated staphylococci were agglutinated specifically by rotavirus present
      in faecal samples within one or two minutes. A total of 1332 stool specimens were
      tested by co-agglutination and ELISA, of which 210 (15.77%) were positive by
      ELISA and 276 (20.72%) by co-agglutination test. Compared to ELISA, sensitivity
      of co-agglutination test was 76.19%, specificity 89.66% and predictive values of
      a positive and a negative test were 57.97% and 95.26% respectively. The results
      indicate that the co-agglutination test is a simple and suitable technique for
      rapid screening of rotavirus infection which could be adopted in clinical
      practice.

PMID- 7575339
TI  - Study on Mycobacterium tuberculosis: the primary drug resistance pattern.
AB  - The study was carried out to investigate the primary drug resistance pattern of
      tubercle bacilli isolated from the pulmonary tuberculosis patient attended in
      Shyamoli TB clinic, Dhaka. Sputum from 961 suspected tuberculous patients were
      randomly collected and stained by Ziehl-Neelsen (Z.N) stain. 135 were
      microscopically positive for Acid Fast Bacilli (AFB). Among them 30 patients were
      excluded from the study as they received antitubercular treatment before. So only
      105 microscopically positive cases were cultured on Lowenstein-Jensen (L-J) media
      and 100 showed pure growth and rest 5 were contaminated with fungus. These 100
      cases were studied on 4 antitubercular drugs. Out of these 100 isolates, 91 were
      M. tuberculosis and rest 9 in the nonchromogen group of mycobacteria other than
      tuberculosis (MOTT) species. Among 91 M. tuberculosis species, 89 (97.80%) to
      Isoniazid (INH), 73 (80.21%) to Rifampicin (RMP) and 91 (100%) to Streptomycin
      (SM) and Ethambutol (ETHM) were sensitive. Of the 9 MOTT species, 4 (44.44%) to
      SM, 7 (77.78%) to ETHM were sensitive and all (100%) were resistant to INH and
      RMP. Among the 100 isolates, 27 (18 M. tuberculosis and 9 MOTT) were resistant to
      4 drugs either single or in combination. Of the 18 (66.67%) M. tuberculosis
      species, 16 (59.26%) to RMP, and 2 (7.41%) to RMP and INH were resistant. Of the
      9 (33.33%) MOTT species, 4 (14.81%) to RMP and INH, 3 (11.11%) to RMP, INH and SM
      and 2 (7.41%) to RMP, INH, SM and ETHM were resistant.

PMID- 7575340
TI  - Disability problem in a rural area of Bangladesh.
AB  - For prevalence and pattern of disability as well as the socio-economic effects of
      disability, a community based study was carried out in a rural area of
      Bangladesh. A trained physician conducted a house to house survey in a population
      of 1906. An overall prevalence of disability of 8.5 percent was found. Major
      forms of disability were hearing disability (23%), visual disability (21%) and
      movement disability (15%). Disability was found to have considerable effects on
      educational attainment, employment and marriage. Many of these disabilities could
      be prevented by simple measures such as immunization, vitamin A supplementation
      and improving referral systems for early treatment. A substantial proportion
      could also benefit from relatively simple rehabilitatory measures.

PMID- 7575341
TI  - Common aerobic bacteria in post operative wound infection and their sensitivity
      pattern.
AB  - Two hundred and four post-operative patients were examined and pus samples were
      collected with sterile cotton swabs from 64 patients with infected wounds. The
      samples were cultured aerobically and the isolates were identified as per
      standard methods. The prevalence rate of post-operative wound infection were
      31.37% and the total number of bacterial isolates were 76 (37.25%). The isolates
      were identified up to their species level & they were E. coli, Staph. aureus, Kl.
      Pneumoniae, Ps. aeruginosa. Pr. vulgaris and S. pyogenes. Gram negative bacilli
      were the predominant organisms and among them E. coli was the most common. In
      antimicrobial susceptibility test Gentamycin and Cephalexin were found sensitive.

PMID- 7575342
TI  - Does hilly ecology prevent childhood diarrhoea?
AB  - Incidence of reported diarrhoeal diseases in hilly children are not precisely
      known. The pattern of diarrhoeal diseases in the hilly areas of Abha and Khamis
      Moshayet mountainous regions of Saudi Arabia has been studied. These areas are
      situated at 2,000 to 3,200 meters above the sea level and are devoid of river,
      canal or lake. The temperature ranges from 5 degrees C to 30 degrees C and
      humidity 30% to 60% usually. Diarrhoeal patients treated in the six health
      centres were recorded and analyzed for the years 1987-88 and 1989-90. Dysentery
      affected 2.37% of the children giving 0.023 episodes per head per year. It was
      almost uniformly distributed in all age groups but was higher in males 10 years
      and over than in females. Diarrhoea affected 8.00% of the whole population and
      27.44% children giving 0.27 episodes per child per year. In all age groups,
      incidences in male were higher than in female. Incidences of both were higher
      during July to October and lower during March to April. The rate was highest in
      Umme Sarrar PHC area. Overall, 10.35% of the whole population and 30% of the
      children contracted diarrhoeal diseases. The episode of reported cases per child
      (0.30) per year was one-seventh of the Saudi national door-to-door survey
      findings (2.07) and one-fourth of the US hospital reported diarrhoea cases. This
      extremely low incidence in the hilly children may be due to hilly ecology, under
      reporting, low rate in the country or a combination of all. Further studies are
      needed in hilly areas of Bangladesh.

PMID- 7575343
TI  - Perception of indoor patients on the services of some Thana Health Complexes.
AB  - In order to find out the level of perception of the indoor patients with regard
      to physical examination of the patients, receipt of medicine, quality of diet,
      overall service satisfaction and behaviour of health personnel, the present study
      was conducted. A total of 102 patients of indoor department of three Thana Health
      Complexes were interviewed by structured questionnaire. The study revealed that
      20.59% respondents were fully satisfied, 50% were partially satisfied and 29.41%
      were not satisfied with indoor department of the Thana Health Complex (THC). The
      major factors responsible for dissatisfaction were identified as non availability
      of medicine, bad behaviour of health personnel other than doctors and non
      availability of staff during necessity. It was found in the study that 6.86% of
      patients received all prescribed medicines from the THC, 14.7% patients received
      most of the prescribed medicine, 28.13% patients did not receive any kind of
      medicine and 50% received very small amount of medicine from the THC.

PMID- 7575344
TI  - Role of a large plasmid in mediation of multiple drug resistance in Salmonella
      typhi and paratyphi A in Bangladesh.
AB  - From 405 patients of suspected typhoid fever, 94 Salmonella typhi and 17
      Salmonella paratyphi A, were isolated from blood and/or stool at the Institute of
      Postgraduate Medicine and Research, Dhaka during March 1992 to February 1993.
      Forty seven percent of the isolates were resistant to multiple drugs which
      included amoxicillin, ampicillin, chloramphenicol and co-trimoxazole. A large
      plasmid of 140 MDa was isolated from 73% of multidrug resistant (MDR) strains.
      However, no plasmid was isolated from any of the strains sensitive to above
      mentioned antibiotics. Majority of MDR Salmonella transferred resistance to E.
      coli K-12 (Lac+, F-, NxR.) by conjugation method. The transconjugants were
      similarly resistant to multiple drugs. All Salmonella were sensitive to
      ciprofloxacin and ceftriaxone.

PMID- 7575345
TI  - Cytokines, differentiation and functions of subsets of CD4 and CD8 T cells.

PMID- 7575346
TI  - Biology of natural and recombinant soluble interleukin-4 receptor.

PMID- 7575347
TI  - Therapeutic interference with interferon-gamma (IFN-gamma) and soluble IL-4
      receptor (sIL-4R) in allergic diseases.
AB  - Allergic sensitization is controlled by CD4+ T cells. A complex interaction
      between antigen-presenting cells, T- and B-cells results in the production of
      (allergen) specific IgE. Analysis of the lymphokine profile of lymphocytes from
      patients with bronchialasthma and atopic dermatitis revealed an imbalance in
      cytokine production. An enhanced production of IL-4 was accompanied by low or
      absent amounts of IFN-gamma. Since both cytokines play a central role in the
      regulation of IgE, it was examined whether therapeutic interference on the level
      of cytokine production may provide an useful tool to alter lymphocyte functions
      in allergic diseases. Two different model systems were employed to study the
      effects of soluble IL-4R (sIL-4R) under in vitro and in vivo conditions. (1) A
      mouse model system for allergic sensitization and increased airways
      responsiveness (AR) was employed to examine whether in vivo treatment with
      recombinant murine sIL-4R may prevent the development of allergic sensitization.
      It was found that local treatment through the airways and the lung as carried out
      by aersolization of the receptor offered a route of application that prevented
      the development of allergen-induced and allergen-dependent immediate
      hypersensitivity responses including the development of increased AR. (2). The in
      vitro effects of humans sIL-4R on functions of mononuclear cells prepared from
      two patients with most severe atopic dermatitis were examined. Incubation of
      lymphocytes with allergens in the presence and absence of sIL-4R indicated that
      the soluble receptor suppressed allergen-induced lymphocyte proliferation and
      allergen-dependent IgE, IgG and IgM production. In addition a complete
      suppression of allergen-specific IgE production was detected in the presence of
      sIL-4R. These data suggest that sIL-4R may provide a useful drug to modify
      lymphocyte-dependent immune functions in allergic diseases.

PMID- 7575348
TI  - Molecular mechanisms of APO-1/Fas(CD95)-mediated apoptosis in tolerance and AIDS.
AB  - The cell surface molecule APO-1/Fas(CD95), a member of the Tumor Necrosis Factor
      (TNF) receptor/Nerve Growth Factor (NGF) receptor superfamily mediates apoptosis
      upon cross-linking by agonistic antibodies or its ligand. Recent findings suggest
      that APO-1/Fas(CD95) and its ligand are the key molecules for antigen receptor
      induced apoptosis in activated mature T cells. Here we propose a mechanism for
      antigen receptor-induced apoptosis of activated T cells via APO-1 ligand mediated
      autocrine suicide. This mechanism may also contribute to the depletion of CD4+ T
      cells in AIDS.

PMID- 7575350
TI  - Avery-Landsteiner Prize awarded to Tim R. Mosmann, professor and chairman of the
      Department of Immunology of the University of Alberta in Edmonton/Alberta,
      Canada.

PMID- 7575349
TI  - Monomeric and dimeric forms of soluble receptors can differ in their
      neutralization potential.
AB  - Recombinant soluble forms of transmembrane receptors can be produced in monomeric
      and dimeric versions. Binding affinity and neutralization potential of these
      different forms of soluble receptors depend on the quaternary structure of their
      ligands. Monomeric ligands will be bound with equal affinity by both forms,
      whereas trimeric ligands, e.g. members of the tumor necrosis factor family of
      ligands, interact with much higher affinity with dimeric soluble receptors than
      with monomeric ones.

PMID- 7575351
TI  - Signal transduction by the IL-1 type I receptor: evidence for the involvement of
      a receptor-coupled protein kinase.
AB  - A novel serine/threonine specific protein kinase was found to be associated with
      the type I IL-1 receptor in the murine T cell lines D10N and EL-4. This kinase
      was identified in immunoprecipitates from IL-1 stimulated T-cells by its ability
      to phosphorylate exogenous substrates in the presence of radiolabeled ATP. An
      endogenous protein, most likely a member of the IL-1 R1 complex, was also
      phosphorylated. The activation of the kinase is specific for IL-1, neither TNF
      nor phorbol esters were able to activate the IL-1 RI associated kinase activity.
      The IL-1 receptor antagonist had no intrinsic activity and inhibited the
      activation of the kinase. The activation of the kinase was rapid and detectable
      after 30 seconds of IL-1 stimulation. A minimal model of the IL-RI signal
      transduction complex is discussed, presenting this novel serine/threonine kinase
      as a constituent of the complex.

PMID- 7575352
TI  - Regulation of IL-1 activity by soluble IL-1 receptors.

PMID- 7575353
TI  - Converging and diverging properties of human interleukin-4 and interleukin-10.
AB  - IL-4 and IL-10 are both produced by activated TH2 cells as well as basophil/mast
      cells. In addition, IL-10 is secreted by activated B cells, monocytes/macrophages
      and keratinocytes. IL-4 and IL-10 act in concert to induce activated B
      lymphocytes to grow, switch isotype and ultimately differentiate into antibody
      producing plasma cells. Both IL-4 and IL-10 inhibit the secretion of
      proinflammatory cytokines by monocytes/macrophages and neutrophils. While IL-4
      enhances the presentation of antigen by monocytes/macrophages and dendritic
      cells, IL-10 inhibits it. IL-4 and IL-10 can either stimulate or inhibit T cell
      proliferation. While both cytokines may prove useful in the management of
      inflammatory disorders, IL-4 is presently used in clinical trials that relate to
      its antitumor effects.

PMID- 7575354
TI  - A molecular basis for T-dependent B cell activation.
AB  - This review has concentrated on the key molecules which regulate T-dependent B
      cell activation in the context of the structural architecture within secondary
      lymphoid tissue where B cell immune responses occur. CD40L clearly plays a key
      role in driving B cells to proliferate within germinal centers, and although the
      data is conflicting, there is some evidence that the induction of CD40L is
      dependent on costimulation through CD28.

PMID- 7575355
TI  - Activation of gene transcription by IL-4, IL-13 and IFN-gamma through a shared
      DNA binding motif.
AB  - Both interleukin-4 (IL-4) and interleukin-13 (IL-13) induce the transcription
      factor NF-IL4 (nuclear factor IL-4) which preexists in an inactive form and binds
      to an IL-4 responsive element (IL-4RE) in the promoter regions of IL-4/IL-13
      dependent genes. UV-crosslinking and SDS gel electrophoresis indicate that NF-IL4
      consists of at least two DNA-binding components of 50 kDa and 100-130 kDa. The IL
      4 responsive element is also recognized by an interferon-gamma (IFN-gamma)
      induced DNA binding protein for which a Mr of 50 kDa has been determined. A
      common DNA binding motif for different transcription factors might provide the
      basis for the frequently observed functional antagonism between IL-4/IL-13 and
      IFN-gamma. The activation of transcription factors by IL-4/IL-13 and IFN-gamma
      could be blocked by inhibitors of tyrosine kinases and ser/thr phosphatases but
      not by a PKC inhibitor, suggesting related signal transduction pathways for these
      cytokines.

PMID- 7575357
TI  - A genetic approach for the analysis of cytokine function in vivo.

PMID- 7575356
TI  - Antagonistic mutant proteins of interleukin-4.
AB  - Interleukin-4 is a major regulator of the immune system, directing e.g. induction
      of a TH2 phenotype in T-cells, activation of B-cells and synthesis of IgE type
      antibodies, which are associated with allergic responses. Site-directed
      mutagenesis has revealed two sites important for receptor interaction on IL-4:
      site I mediates binding to the IL-4 receptor alpha subunit, and site II is
      involved in signal transduction through the receptor complex. Specific mutations
      in site II produced a series of ligands which bound to the receptor with high
      affinity, but had little or no agonistic activity and inhibited effects of wild
      type IL-4. The closely related cytokine IL-13, also a mediator of allergic
      processes, is antagonized as well. Antagonistic site II mutants of human IL-4 are
      therefore effective inhibitors with therapeutic potential for IL-4 associated
      diseases like type I hypersensitivity and asthma.

PMID- 7575358
TI  - How cytokines control immunoglobulin class switching.
AB  - B lymphocytes can alter the class of antibody they produce by immunoglobulin
      class switch recombination. This recombination is targeted by distinct cytokines
      to particular switch regions. Prior to switch recombination, the same cytokines
      induce transcription through the targeted switch regions and generate IH "switch"
      transcripts. To show whether the two events are functionally related, we have
      replaced the endogenous interleukin-4 (IL-4) dependent promoter of murine I gamma
      1 switch transcripts by an heterologous promoter, the human metallothionein IIA
      (hMT) promoter. Indeed, switch recombination can be targeted to IgG1 by the hMT
      promoter. In mutant mice, which cannot generate processed switch transcripts,
      switch recombination cannot be targeted to IgG1 by the hMT promoter. Thus, IL-4
      targets switch recombination to IgG1 by induction of processed switch
      transcripts.

PMID- 7575359
TI  - Selection for increased female sexual receptivity in raised stocks of Drosophila
      melanogaster.
AB  - Two third-chromosome mutations in raised (rsd) stocks, when homozygous, cause the
      wings of Drosophila melanogaster adults to be held upright. Males expressing
      these mutations cannot vibrate their wings to produce the courtship song, which
      functions to increase female receptivity to copulation. As expected, rsd males
      are less successful when courting wild-type females. However, females from long
      established rsd stocks are more receptive to courtship stimuli and mate more
      readily with both rsd and wild-type males than do wild-type females. Genetic
      analysis reveals dominant factors on the X and third chromosomes that, in
      combination, are responsible for the increased receptivity of rsd females. These
      observations suggest that the lack of courtship song in rsd stocks, which would
      be expected to reduce the vigor of the stock, may have functioned as a selective
      force, favoring mutations that increased female receptivity. Possible
      consequences of selection favoring the development of differential female
      receptivity on speciation are discussed.

PMID- 7575360
TI  - Multiple raters of disruptive child behavior: using a genetic strategy to examine
      shared views and bias.
AB  - Most research on child behavior incorporates information from different
      individuals. While agreement between informants is generally only modest, there
      is little understanding of the processes underlying disagreement. In twin
      studies, differential agreement among raters for MZ and DZ twins is of particular
      concern. The processes underlying differences among mother, father, and child
      ratings of oppositional and conduct disorder symptoms are explored. Evidence in
      favor of a shared parental view of behavior is presented. Parental ratings give
      higher intrapair correlations, which could be due to either parents rating their
      twins more similarly or twins contrasting themselves. Rater bias and situational
      specificity are among the possible explanations of differential ratings. The
      effects of incorporating multiple raters of behavior on estimates of genetic and
      environmental effects are explored. These suggest that genetic influences are
      greater for the shared (multiple-rater) phenotype than for individual ratings;
      reduction in measurement error is only a partial explanation.

PMID- 7575361
TI  - Physical similarity and the equal-environment assumption in twin studies of
      psychiatric disorders.
AB  - The equal-environment assumption (EEA), upon which twin methodology is based, was
      examined for the impact of physical similarity on phenotypic resemblance in five
      common psychiatric disorders: major depression, generalized anxiety disorder,
      phobia, alcoholism, and bulimia. A population-based sample of 882 female-female
      twin pairs of known zygosity was rated for similarity of appearance by color
      photographs. Psychiatric diagnoses were made by clinical assessment of personal
      interviews of the twins. Structural equation modeling of the data using physical
      similarity as a form of specified common environment provided no evidence for a
      significant effect of physical resemblance on concordance for major depression,
      generalized anxiety disorder, phobia, and alcoholism, thereby supporting the
      validity of the EEA in twin studies of these disorders. Results for bulimia, on
      the other hand, suggest, within the limitations of this study, that physical
      similarity may significantly influence twin resemblance for this disorder.

PMID- 7575362
TI  - Unequal rate of monozygotic and like-sex dizygotic twin birth: evidence from the
      Minnesota Twin Family Study.
AB  - It is generally believed that in Caucasian populations the rate of monozygotic
      (MZ) twinning is approximately equal to the rate of like-sex dizygotic (DZ)
      twinning so that representative samples of like-sex twins should contain
      approximately equal numbers of MZ and DZ twins. Recent evidence suggests,
      however, that the rate of DZ twinning in Caucasian populations has declined over
      the past 50 years so that there are now many more MZ than like-sex DZ twin births
      (Jeanneret and MacMahon, 1962; James, 1972; Mosteller et al., 1981; Doherty and
      Lancaster, 1986; Lykken et al., 1990). We report additional evidence of a higher
      rate of MZ than like-sex DZ twinning from Minnesota for the birth years 1971
      1984. The convergence of evidence thus suggests that the observation of a greater
      number of MZ than DZ twins in a volunteer twin sample can no longer necessarily
      be taken as a sign of ascertainment bias.

PMID- 7575363
TI  - Genetic analysis of peripheral nerve conduction velocity in twins.
AB  - We studied variation in peripheral nerve conduction velocity (PNCV) and
      intelligence in a group of 16-year-old Dutch twins. It has been suggested that
      both brain nerve conduction velocity and PNCV are positively correlated with
      intelligence (Reed, 1984) and that heritable differences in NCV may explain part
      of the well established heritability of intelligence. The Standard Progressive
      Matrices test was administered to 210 twin pairs to obtain IQ scores. Median
      nerve PNCV was determined in a subgroup of 156 pairs. Genetic analyses showed a
      heritability of 0.65 for Raven IQ score and 0.77 for PNCV. However, there was no
      significant phenotypic correlation between IQ score and PNCV.

PMID- 7575364
TI  - A multivariate genetic analysis of sensation seeking.
AB  - The genetic architecture of sensation seeking was analyzed in 1591 adolescent
      twin pairs. Individual differences in sensation seeking were best explained by a
      simple additive genetic model. Between 48 and 63% of the total variance in
      sensation seeking subscales was attributable to genetic factors. There were no
      sex differences in the magnitude of the genetic and environmental effects. The
      different dimensions of sensation seeking were moderately correlated. The
      strongest correlations were between the subscales Thrill and Adventure Seeking
      and Experience Seeking (r = 0.4) and between Boredom Susceptibility and
      Disinhibition (r = 0.4 in males, r = 0.5 in females). A triangular decomposition
      showed that the correlations between the sensation seeking subscales were induced
      mainly by correlated genetic factors and, to a smaller extent, by correlated
      unique environmental factors. The genetic and environmental correlation
      structures differed between males and females. For females, higher genetic
      correlations for Experience Seeking with Boredom Susceptibility and Disinhibition
      and higher correlations among the unique environmental factors were found. There
      was no evidence that sex-specific genes influenced sensation seeking behavior in
      males and females.

PMID- 7575365
TI  - Intermale aggression tested in two procedures, using four inbred strains of mice
      and their reciprocal congenics: Y chromosomal implications.
AB  - Indications of a role for the nonpseudoautosomal region of the Y chromosome
      (YNPAR) in intermale attack behavior have been demonstrated by Maxson's group
      using C57BL/10 (B10) and DBA/1 (D1) inbred mouse strains and their reciprocal
      congenics. Carlier and Roubertoux' group, using CBA/H (H) and NZB/B1NJ (N) mice,
      did not find such a YNPAR effect. For the two research groups, however, not only
      were the parental strains different, but also the rearing conditions and testing
      methods. The divergent conclusions drawn may therefore have been due either to
      genetic variation or to environment-related variables. We carried out two
      experiments to investigate these alternatives. The N and H strains were raised
      and tested according to the experimental design used by Maxson's group
      (homogeneous set test) and the D1 and B10 strains were raised and tested
      according to the experimental design of Carlier and Roubertoux' group (standard
      opponent test). Considering all studies together, the YNPAR effect appeared in
      both sets of mice only when using the homogeneous set test. This raises the
      question of what environmentally related variables are involved in the YNPAR
      effect on intermale attack. One strong hypothesis is that the different types of
      opponents in each experimental design send differing olfactory signals, which, in
      turn, differentially affect the capacity to elicit intermale attack behavior.

PMID- 7575366
TI  - Predatory aggression in male mice selectively bred for isolation-induced
      intermale aggression.
AB  - Male mice differing in their genetically determined disposition for isolation
      induced intermale aggression were compared on behaviors related to predatory
      aggression. An ongoing sequence of selective breeding established high-aggressive
      (Turku Aggressive: TA) and low-aggressive (Turku Non-Aggressive: TNA) lines from
      an outbred Swiss albino foundation stock. The parental strain, designated the
      Normal (N) strain, has been kept as a control line and is bred without regard to
      aggressiveness. Testing consisted of dropping a live cricket into the home cage
      of the individually housed experimental mice. Results showed that the TA males
      displayed shorter latencies to attack and spent more time in chasing, attacking,
      and consuming crickets than did TNA and N males. The TNA males displayed
      significantly less predatory aggression than both the TA and N males. When
      brothers of the males tested for predatory aggression were tested for intermale
      aggression, a similarly significant effect of breeding line was obtained for the
      latency to attack. Testing consisted of placing an intact male mouse into the
      cage of the male to be tested. The results suggest that there may be parallels in
      genetic variation between intermale and predatory attacking.

PMID- 7575367
TI  - Studies on wild house mice (VIII): Postnatal maternal influences on intermale
      aggression in reciprocal F1's.
AB  - Previous findings have shown a difference in attack latencies, i.e., aggression,
      between reciprocal F1's of a line selected for short attack latency (SAL) and a
      line selected for long attack latency (LAL). In the present study, we
      investigated the influence of postnatal maternal environment on attack latency
      scores (ALSs). The results show that only the evolution of the ALSs over 3
      consecutive days is influenced by crossfostering. Accordingly, we conclude that
      the postnatal maternal environment affects ALSs only to a small extent.

PMID- 7575369
TI  - Organization of motor and posture patterns in paradise fish (Macropodus
      opercularis): environmental and genetic components of phenotypical correlation
      structures.
AB  - Paradise fish exhibit complex, environment-specific behavioral responses which
      consist of behavioral elements (motor and posture patterns) appearing in a
      typical, correlated manner. The genetic and environmental components underlying
      these phenotypical correlations have not been comprehensively investigated.
      Therefore, we have analyzed the behavioral elements of paradise fish from the
      nine populations of a 3 x 3 full diallel cross by employing a bivariate extension
      of the Hayman-Jinks variance-covariance analysis, demonstrating the presence of
      significant environmental and genetic correlations. To investigate the
      multivariate structure of the correlation matrices obtained, we subjected the
      phenotypical, environmental, additive genetic, and dominance correlations to
      principal-component analyses (PCAs). After rotation, the phenotypical principal
      factor pattern found was similar to previously obtained ones, suggesting stable
      underlying biological mechanisms. The environmental PCA extracted several
      environmental principal factors that were highly situation-specific. PCAs of the
      matrices of genetic correlations extracted only a small number of genetic
      principal factors which were not situation-specific, suggesting a relatively
      simple underlying genetic structure.

PMID- 7575368
TI  - Genetic analysis of the relationships between behavioral and neuroendocrine
      traits in Roman High and Low Avoidance rat lines.
AB  - In order to determine whether the coselection observed between the selection
      trait (active avoidance behavior) of the Roman High Avoidance (RHA) and Roman Low
      Avoidance (RLA) rat lines and their neuroendocrine characteristics were
      genetically determined, we analyzed, in nonsegregating (RHA, RLA, and F1) and
      segregating (F2 and the two backcrosses) crosses, the inheritance pattern and the
      phenotypic correlations among behavioral (shuttle-box behavior), physiological
      (body, adrenal, and thymus weights), and neuroendocrine (corticosterone and
      prolactin reactivity, catecholamine enzyme activities) variables. Physiological
      characteristics and enzyme activities have a crucial role in sex dissociation.
      Avoidance behavior and prolactin reactivity to novel environment remained
      associated in segregating crosses despite gene rearrangement. They represented
      the most important variables to differentiate the Roman lines, perhaps sharing a
      common regulatory mechanism under genetic control.

PMID- 7575370
TI  - Oligogenic determination of morphine analgesic magnitude: a genetic analysis of
      selectively bred mouse lines.
AB  - Two ongoing selective breeding projects have produced mice that display divergent
      analgesic responses to morphine. These two projects have selected for similar
      phenotypes: high and low levorphanol analgesia (HAR/LAR lines; Portland, OR) and
      high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland).
      Evidence suggests genetic commonalities between mice of the two projects. Using a
      Mendelian breeding protocol, we have recently found that one or two genetic loci
      predominantly determine the high morphine analgesia exhibited by HA mice. In the
      present study we demonstrate that the differential morphine analgesia (5 mg/kg,
      i.p.) displayed by HAR and LAR mice is similarly oligogenic, predominantly
      determined by two unlinked loci. A complementation analysis, in which the
      analgesic responses to morphine of the recessive homozygotes of each project (HAR
      and HA) were compared to those of their hybrid offspring (HAR x HA), revealed
      that different genetic loci have been fixed in each project. An intriguing
      bimodal distribution was observed in the HAR x HA population: Some HAR x HA
      hybrids displayed greater morphine analgesia than either HAR or HA mice, whereas
      others displayed minimal analgesia. LAR x LA hybrids displayed less analgesia
      than either LAR or LA mice. The analgesic responses of HAR x LA and LAR x HA mice
      were comparable to those of their low-line parents. These findings indicate not
      only that different loci were responsible for producing high morphine responders
      in each selection project but that these distinct loci can interact
      synergistically to produce "superhigh" and "superlow" responders.

PMID- 7575371
TI  - Modulation of action potential duration by inhibition of the transient outward
      current in sheep cardiac Purkinje fibers.
AB  - In sheep cardiac Purkinje fibers concentration-dependent inhibition of transient
      outward current (ito) by 4-aminopyridine (4-AP, 3-1000 mumol/l) was recorded with
      the two-microelectrode voltage-clamp technique, and correlated effects on action
      potential duration measured at -70 mV (APD-70) were investigated. Half-maximal
      inhibition of ito-amplitude occurred at 15 mumol/l 4-AP. The drug exhibited no
      major effect on voltage-dependent control of inactivation but reduced the
      maximally available ito-current. At different activation frequencies (0.05 Hz,
      0.25 Hz, 1 Hz) an equal amount of ito-current, measured as percentage of the
      respective control, was inhibited by 4-AP. The APD-70 was on the average
      increased by 4-AP (3-500 mumol/l) in a concentration-dependent manner up to 151%
      of control. The drug-induced prolongation, measured as percentage of the
      respective control, was independent of stimulation frequency (0.05 Hz, 0.25 Hz, 1
      Hz). Prolongation of APD-70 was on the average more pronounced for short action
      potentials (APD-70 < 150 ms: 169% of reference) than for longer ones (APD-70 150
      300 ms: prolongation to 117% of reference; 500 mumol/l 4-AP; 0.25 Hz stimulation
      rate). Few long control signals (APD-70 > 300 ms) were shortened by 4-AP. These
      results indicate that inhibition of ito-current by appropriate drugs will result
      in a reduction of inhomogeneity of action potential duration.

PMID- 7575372
TI  - I(f) current mediates beta-adrenergic enhancement of heart rate but not
      contractility in vivo.
AB  - BACKGROUND: The hyper-polarization-activated "I(f)" current in the sinoatrial
      (SA) node participates in the spontaneous diastolic depolarization responsible
      for pacemaking function. Both sympathetic and parasympathetic control of heart
      rate is thought to involve modulation of I(f). This study tested whether beta
      adrenoceptor activation of heart rate, but not contractile state, could be
      reduced by blockade of I(f) channels in the intact, anesthetized pig. METHODS:
      Both isoproterenol (ISO, 0.1 micrograms/kg/min i.v. for 5 min) and norepinephrine
      (NE, 0.3 micrograms/kg/min i.v. for 5 min) were used sequentially to activate
      beta-adrenoceptors in five metomidathydrochloride-anesthetized pigs. Left
      ventricular pressure and dP/dt, aortic blood pressure and cardiac output were
      measured. I(f) channels were then blocked selectively with 0.3 mg/kg i.v.
      zatebradine (ULFS49) and the test doses of ISO and NE were repeated. Following a
      further high dose (10 mg/kg, i.v.) of zatebradine, the test doses of ISO and NE
      were repeated once again. RESULTS: Before I(f) blockade, ISO and NE elicited
      reproducible increases in both heart rate and left ventricular dP/dt. Whereas NE
      caused an increase in both systolic (56%) and diastolic (53%) aortic pressure and
      a modest heart rate increase (22%), ISO caused a decrease in diastolic aortic
      pressure (-22%) and a marked increase in heart rate (81%). Low dose zatebradine
      reduced basal heart rate from 98 +/- 6 to 66 +/- 3 bpm, p < 0.05; cardiac output
      fell by 20%, stroke volume increased by 18% and total peripheral resistance was
      unchanged. ISO after low-dose zatebradine still elicited marked increases in
      heart rate (66 +/- 3 to 105 +/- 5 bpm, p < 0.05) and left ventricular dP/dt (774
      +/- 94 to 3364 +/- 206 mmHg/s, p < 0.05) and reduced aortic diastolic pressure
      (37 +/- 2 to 33 +/- 1 mmHg, p < 0.05). NE after low-dose zatebradine increased
      heart rate (73 +/- 4 to 89 +/- 5 bpm, p < 0.05), left ventricular dP/dt (810 +/-
      95 to 3372 +/- 196 mmHg/s, p < 0.05) and both systolic and diastolic aortic
      pressures. High dose zatebradine caused no further reduction in heart rate (77 +/
      4 vs 82 +/- 6 bpm, NS) but left ventricular dP/dt decreased (798 +/- 92 to 418
      +/- 50 mmHg/s, p < 0.05) as did both systolic and diastolic aortic pressures.
      Subsequent administration of ISO had no effect on heart rate but increased left
      ventricular dP/dt from 418 +/- 50 to 3468 +/- 256 mmHg/s (p < 0.05) and systolic
      aortic pressure increased from 58 +/- 7 to 90 +/- 3 mmHg (p < 0.05). NE
      administered after high dose zatebradine also increased left ventricular dP/dt
      (580 +/- 54 to 2608 +/- 182 mmHg/s, p < 0.05) while heart rate fell (86 +/- 4 to
      74 +/- 6 bpm, p < 0.05). Both systolic and diastolic aortic pressures increased
      substantially during the NE infusion after high dose zatebradine. CONCLUSION:
      Zatebradine dose-dependently inhibits beta-adrenoceptor-mediated heart rate
      increases while leaving beta-adrenoceptor-mediated increases in myocardial
      contractile state intact. This observation can be explained by a selective
      blockade of the hyperpolarization-activated current I(f) by low concentrations of
      the drug.

PMID- 7575373
TI  - Disruption of sarcolemmal integrity during ischemia and reperfusion of canine
      hearts as monitored by use of lathanum ions and a specific probe.
AB  - Myocellular injury induced by acute ischemia and subsequent reperfusion was
      studied in 38 dogs, with special reference to sarcolemmal permeability as
      determined by the vital ionic lanthanum (La3+) probe technique and electron
      microscopy. The left anterior descending coronary artery (LAD) was occluded in 14
      dogs for 10 to 60 min, and the ischemic zone was perfused slowly for 7 min with a
      La(3+)-containing solution. In 21 dogs, the LAD was released for 10 min after
      occlusion and was then reperfused for 7 min with arterial blood plus the La(3+)
      containing solution. Subsequently, in both groups of animals, the ischemic
      myocardium was subjected to perfusion fixation in preparation for electron
      microscopy. In normal cardiac myocytes, La3+ was localized exclusively in the
      extracellular space. After 10 to 20 min of ischemia, more than 80% of myocytes
      appeared normal or were damaged only slightly, and the majority continued to
      exclude La3+. After 10 min of ischemia, deposits of lanthanum were detected in 1
      and 6% of myocytes in the absence or presence of reperfusion, respectively. The
      number of cells with such deposits was markedly increased after 30 min of
      ischemia (19%), as well as after 20 min of ischemia followed by reperfusion
      (17%), prior to the development of irreversible myocardial damage. After 60 min
      of ischemia with or without reperfusion, about 30% of myocytes showed severe
      injury with particulate deposits of lanthanum throughout the entire cell. These
      results indicate that sarcolemmal permeability increases during the early stage
      of myocardial injury due to ischemia or ischemia-reperfusion and contributes to
      the development of myocardial damage.

PMID- 7575374
TI  - Efflux of adenosine and total adenylate catabolites during alterations of the
      cellular energy state. An NMR study of continuous and discontinuous ischemia.
AB  - Reperfusion after continuous or discontinuous ischemia has a bearing on clinical
      interventions. An important question is the washout of metabolites after periods
      of diminished energy state of the myocardial cell. We therefore set out to
      determine the washout of adenosine and its metabolites after periods of ischemia
      in an experimental set-up which allowed non-destructive monitoring of the
      cellular energy state and cytosolic pH over consecutive time intervals. Isolated
      rat hearts were perfused with hemoglobin-free saline in a nuclear magnetic
      resonance spectrometer equipped for 31P NMR spectroscopy of phosphorus-containing
      metabolites, which could be measured over 3-min time blocks. The response of the
      heart when subjected to 18 min of continuous ischemia and subsequent reperfusion
      was compared with that when subjected to three 6-min periods of ischemia
      separated by 3-min periods of reperfusion. The mechanical performance of the
      hearts, oxygen consumption and efflux of adenosine and its metabolites were
      measured. The consecutive ischemic periods produced no evidence of
      preconditioning as judged from the cellular energy state, although the mechanical
      recovery was better than after continuous ischemia. During the repetitive
      ischemia/reperfusion protocol the efflux of adenosine was smaller, although the
      efflux of combined adenylate catabolites did not differ from that after
      continuous ischemia. The results do not support the view of adenosine being a
      major effector in the phenomenon of preconditioning.

PMID- 7575375
TI  - Energy metabolism, intracellular Na+ and contractile function in isolated pig and
      rat hearts during cardioplegic ischemia and reperfusion: 23Na- and 31P-NMR
      studies.
AB  - The purpose of the study was to compare the role of Na ions in the damage caused
      by cardioplegic ischemia in fast (rat) and slow (pig) hearts. Changes in
      intracellular Na+ (Na+i), high energy phosphates, and contractile function were
      assessed during ischemia (36 degrees C) and reperfusion in KCl-arrested perfused
      hearts using 31P-NMR and shift reagent (DyTTHA3-)-aided 23Na-NMR spectroscopy. In
      the pig hearts the rates of decrease of phosphocreatine (PCr), ATP and
      intracellular pH (pHi) were 3-4 times slower than the rates observed in the rat
      hearts. In the pig hearts PCr was observable (approximately 10%) during first 80
      min of the ischemic period (90 min). Comparable decreases in ATP (32.0 +/- 6 vs.
      38 +/- 15% of initial) and pHi, (to 6.14 +/- 0.06 vs. 6.10 +/- 0.15) observed
      after 90 and 20 min ischemia in pig and rat hearts, respectively, were associated
      with a smaller Na+i increase in the pig hearts (to 175 +/- 31%) than in the rat
      hearts (to 368 +/- 62%). This Na+ increase in the rat hearts preceded development
      of ischemic contracture (41 +/- 6 mmHg at 23.6 +/- 0.7 min) while no contracture
      was observed in pig hearts. Reperfusion of the rat hearts (at 30 min ischemia)
      was followed by partial recovery of PCr (44 +/- 3%) and Na+i (234 +/- 69%) and
      poorer recovery of the pressure-rate product (PRP, 9 +/- 4%) and end-diastolic
      pressure (EDP, 72 +/- 5 mmHg) compared to the pig hearts (PCr, 106 +/- 25%; Na+i,
      82 +/- 17%; PRP, 24 +/- 3%; EDP, 4.6 +/- 2.5 mmHg). The loss of function in the
      pig hearts was reversed by increasing Ca++ in the perfusate from 1 to 2.3 mM and
      resulted in a rise in both PRP and oxygen consumption rate, V(O2), from 24 +/-
      3.3 to 64.5 +/- 5.8% and from 55 +/- 10 to 74 +/- 10% of the control levels,
      respectively. The PRP/delta V(O2) ratio was halved in the post-ischemic pig
      hearts and returned to the pre-ischemic level following Ca++ stimulation. It is
      suggested that the higher stability of Na+ homeostasis to ischemic stress in the
      pig heart may result from: 1) a lower ratio of the rate of ATP hydrolysis to
      glycolytic ATP production; 2) differences in the kinetic properties of the Na+
      transporters. Reduced Na+ accumulation during ischemia and reperfusion is
      beneficial for metabolic and functional preservation of cardiomyocytes.

PMID- 7575376
TI  - Inhibition of adenosine deaminase and administration of adenosine increase
      hypoxia induced ventricular ectopy.
AB  - Eighteen anesthetized, instrumented beagles (both genders, 10.4 +/- 0.5 kg) were
      used to investigate the effects of administered adenosine (n = 6), erythro-9-(2
      hydroxy, 3-nonyl)adenine (EHNA), a potent inhibitor of endogenous adenosine
      deaminase (n = 6), and saline (n = 6), on the incidence of ventricular
      arrhythmias caused by systemic hypoxia (5% O2, 95% N2, PaO2 = 21 +/- 3 mmHg).
      After dogs were instrumented and monitored variables were in the steady-state,
      the above compounds were infused continuously into the cannulated left anterior
      descending (LAD) coronary artery for three minutes before, and throughout a four
      minute period of hypoxia. After approximately 4 min of hypoxia the rates of
      ventricular ectopy [(total beats-normal beats)/total beats x 100 = % ectopy] were
      73 +/- 9%, 73 +/- 11%, and 35 +/- 8% for the three groups, respectively. The
      percent ectopy of the adenosine- and EHNA-treated dogs was significantly greater
      (p < 0.05) than that for the saline-treated controls. These findings suggest that
      adenosine contributes to the ventricular arrhythmias of experimental systemic
      hypoxia.

PMID- 7575377
TI  - Suppression of reperfusion arrhythmia by ischemic preconditioning in the rat: is
      it mediated by the adenosine receptor, prostaglandin, or bradykinin receptor?
AB  - The mechanism for the suppression of reperfusion arrhythmia by preconditioning
      (PC) remains unknown. This study aimed to examine the roles of the adenosine
      receptor, prostaglandin (PG), and bradykinin (BK) receptor in PC. Under
      pentobarbital anesthesia, the coronary artery of the rat was occluded for 5 min
      and then reperfused. In untreated controls, this protocol induced ventricular
      tachycardia (VT) in 100% of the rats and ventricular fibrillation (VF) in 60%. PC
      with 2 min ischemia/5 min reperfusion prior to the 5 min coronary occlusion
      significantly reduced the incidence of reperfusion VT and VF to 30% and 0%,
      respectively. This antiarrhythmic effect of the PC was not blocked when rats were
      pretreated with 8-phenyltheophylline (8-PT, 10 mg/kg), aspirin-DL-lysin (18
      mg/kg), or a specific BK receptor antagonist, Hoe140 (20 nmol/kg). None of these
      agents alone significantly modified the incidence of reperfusion VT or VF. These
      results suggest that neither the adenosine receptor, endogenous PG, nor BK
      receptor play a major role in the mechanism of suppression of perfusion
      arrhythmias by PC in the rat heart.

PMID- 7575379
TI  - [Causes of illness in young dogs in necropsy files (1980-1993)].
AB  - Between 1980 and 1993 a total of 10,090 dogs was dissected at the Institute for
      Veterinary Pathology of the Freie Universitat of Berlin. 2956 (29.3%) of the dogs
      were younger than 18 months. Age-, breed- and sex distribution as well as death
      causes were examined. The main death causes were viral infectious diseases
      (51.76%), especially parvovirus infections (26.73%), canine distemper (18.81%),
      as well as congenital defects (6.36%). It could be shown that Rottweilers and
      German Shepherds carried an increased risk of parvovirus infections and that
      several miniature breeds showed a propensity for congenital defects.

PMID- 7575378
TI  - Calculated mean arterial pressure in the posterior tibial and radial artery
      pressure wave in newborn infants.
AB  - Mean arterial pressure (MAP) is the area under the pressure wave averaged over
      the cardiac cycle, and therefore depends on pressure wave contour. A generally
      used rule of thumb to estimate MAP of peripheral arteries in adults is adding one
      third of the arterial pulse pressure (PP) to diastolic arterial pressure (DAP).
      As peripheral pressure wave forms in neonates do not resemble adult peripheral
      wave forms, it may be expected that this rule of thumb does not hold for
      neonates. Previously, we found that MAP can be calculated by adding 50% PP to DAP
      in radial artery waves in neonates. In the present study, we investigated in
      neonates how MAP in the posterior tibial artery depends on systolic and diastolic
      pressure and we compared these findings to those found in the radial artery.
      Forty infants admitted for intensive care were studied. We analyzed 5000
      invasively and accurately obtained blood pressure waves in the posterior tibial
      artery of 20 neonates and another 5000 waves similarly obtained from the radial
      artery in another group of 20 neonates. We found that MAP in posterior tibial
      artery waves is well approximated by adding 41.5 +/- 2.0% of PP to DAP, whereas
      MAP in radial artery waves can be calculated by adding 46.7 +/- 1.7% of PP to
      DAP. These values are significantly different (p < 0.0001). In conclusion, the
      rule of thumb as used in the adult to find MAP, where 33% PP is added to DAP,
      does not hold for the newborn. We recommend to calculate MAP in the tibial artery
      by adding 40% of PP to DAP and in the radial artery by adding 50% of PP to DAP.

PMID- 7575380
TI  - [The resistance behavior of significant veterinary bacterial agents in the year
      1992 (ranking in sequence)].
AB  - On the basis of results of sensitivity tests carried out in 1992 by means of a
      standardized agar diffusion test according to DIN 58,940 by 28 laboratories
      performing routine diagnosis, frequency of resistance was evaluated in the form
      of rank orders. For "calculated" chemotherapy, the choice of the substance to be
      applied is determined by the sensitivity of the presumptive pathogen, if
      laboratory results relating to the agent are (still) lacking. Evaluation of the
      pathogens tested (clostridia, E. coli, pasteurellas, salmonellas, staphylococci,
      streptococci) has made it evident that, due to a wide distribution of resistance
      factors against benzylpenicillins, tetracyclines, chloramphenicol, streptomycin,
      macrolides and sulfonamides, the range of antibiotics for the (uncontrolled)
      first application has become even narrower. A testing of the pathogen in the
      antibiogram remains an urgent necessity.

PMID- 7575381
TI  - [Some theoretical aspects of behavior research in domestic animals].
AB  - During the past decade, applied farm animal ethology has become of increasing
      significance within the behavioural sciences. The present paper investigates some
      of the most important terms and concepts of basic behavioural research in order
      to relate these approaches to farm animal ethology. It is advocated here that
      deviations of theoretical frameworks used in basic and applied research should be
      kept at a minimum, unless necessitated by particular aspects of applied research
      goals. It is further argued that environmental requirements of the animals and
      motivational causes of behaviour could be assessed more appropriately when
      considering behaviour as an interaction between organism and environment shaped
      by natural and artificial selection, i.e. as a means to ultimately maximize
      biological fitness. It is concluded that ultimate causation of behaviour should
      become a major focus in applied ethology in order to reach at valid approaches to
      animal welfare and improved husbandry systems which are more in line with the
      actual needs of the animal.

PMID- 7575382
TI  - [Comparative studies of maedi-visna diagnosis: immunodiffusion test, enzyme
      immunoassay, immunoblot].
AB  - The agar gel immunodiffusion test (AGIDT) is applied worldwide for the
      serological field diagnosis of ovine/caprine lentivirus infections (Maedi-Visna
      and Caprine Arthritis-Encephalitis). To a lesser extent, enzyme-linked
      immunosorbent assay (ELISA) systems are in use. The sensitivity and specificity
      of available ELISA systems is strongly influenced by technical details. We
      present here an MVV-ELISA of high sensitivity, which is based on an antigen
      preparation containing a high amount of the major antigenic surface protein gp
      135. This result was achieved by a simple and gentle purification method of
      antigen from whole virus. The test was applied to evaluate the seroprevalence of
      MVV-antibodies in herds derived from eleven farms located in the North-East of
      Germany. Furthermore, the antibody kinetics in experimentally infected sheep was
      investigated. The results were confirmed by internal controls and by immunoblot
      analysis of antibodies against p 28. The ELISA displayed significant differences
      between positive and negative results and identified up to 25% more seropositive
      samples than the AGIDT. Therefore, a final diagnosis of questionable AGIDT
      results was obtained. The specificity of results was confirmed by immunoblots
      with selected sera. We recommend to use the ELISA especially for screening of
      herds and for population controls. In addition, immunoblots are a valuable tool
      to test individual sera from specified cases.

PMID- 7575383
TI  - [Ketamine-midazolam combination for anesthesia of rabbits--results of
      neuroelectrophysiologic studies using evoked potentials].
AB  - The study was done in order to investigate the central nervous activities in
      rabbits (n = 10) during experimental surgery in ketamine and ketamine/midazolam
      anaesthesia. The combination of a benzodiazepine with ketamine was thought to be
      beneficial to reduce the usual excitatory nervous effects after ket amine
      anaesthesia. The results of the measured EEG-power spectra and somatosensory
      evoked potentials were presented. Additionally, the central effects were
      correlated with mean arterial blood pressure and the results of blood gas
      analyzes.

PMID- 7575384
TI  - [Animal welfare laws concerning air transportation of lobsters and langostinos].
AB  - According to scientific understanding the following statements are important to
      assure a successful transportation of crustaceans. 1. An exact definition of the
      kind (species) of lobster to be transported is necessary. 2. Providing a humid
      climate in the containers. 3. Application of ventilation holes of 3 cm size of
      the container. 4. Rinsing with clean oxygen-containing water of the respiratory
      apparatus after transportation. 5. Decapodes are not to be transported during 7
      weeks after skinning. 6. Through adding of iced water in plastic bags a
      temperature of +2 degrees C should be created in the container. 7. No shaking
      during transportation. 8. According to experiences of myself and of that of
      traders too no more than 4 layers of lobsters may be piled up.

PMID- 7575385
TI  - [The suckling behavior and development of biochemical parameters in piglets from
      conditions of group housing of suckling sows: preliminary results].
AB  - The suckling behaviour, the development of daily weight gains and biochemical
      blood parameters (immunoglobulin G, total protein, glucose, urea) were
      investigated during the suckling period (35 days) of piglets (Sus scrofa) in a
      group housing system for nursing sows (group P: 4 primiparous sows, 34 piglets;
      group M: 4 multiparous sows, 43 piglets). Following an imprinting period of 10
      days, piglets were given the opportunity to leave the farrowing pen and to
      interact with the other sows (variant e: suckling bouts at own mother only,
      variant f: suckling bouts also at one or more unfamiliar sows). Although a number
      of piglets suckled at unfamiliar sows (Pf = 73.5%; Mf = 32.5%; p = 0.01), only
      those piglets that stayed with their own mother after mixing had some
      "physiological advantages" (Pe: daily weight gain from day 10 to 35, p = 0.05;
      Me: IgG, p = 0.05). Piglets of primiparous sows had a lower teat pair fidelity
      within the imprinting period (day 1 to 10). During this time, piglets of both
      groups suckling at unfamiliar sows showed a lower teat pair fidelity (P: ns; M: p
      = 0.05), tended to prefer the posterior part of the udder, and their blood
      glucose and urea contents were higher (P: ns; M: p = 0.05). This was interpreted
      as an indication of competitive strain which obviously encouraged the piglets to
      leave their mothers. It is necessary to carry out further systematical studies on
      sociophysiological mechanisms.

PMID- 7575386
TI  - [Diagnosis of trichinellosis in living pigs using indirect ELISA].
AB  - A modified E/S-ELISA based on the procedure described by Gamble et al. (1988) was
      used for the diagnosis of trichinellosis in the domestic pig. The results of
      screening the sera of 92 pigs experimentally infected with Trichinella larvae (T.
      spiralis, T. nativa) with different doses, confirmed that the E/S-ELISA is
      suitable for the serological detection of Trichinella-specific IgG. Although the
      serotest shows a high sensitivity especially in the case of a low infection rate,
      it can not be used as an alternative for traditional meat inspection methods
      because of its so called diagnostic window. On the other hand, this serotest is
      considered to be useful for herd monitoring. False-negative results prior to
      completed seroconversion (the diagnostic window) were in most cases encountered
      up to the 4th-5th week post infection (p.i.), depending on the infectious dose
      used. Due to the prolonged persistence of antibodies, it was possible to
      demonstrate Trichinella infections by serology for a relatively long period (at
      least 80 weeks p.i.). Predictably, all 960 swine sera from the field tested in
      the E/S ELISA were negative for Trichinella. Separation and staining of the E/S
      antigen in SDS-PAGE revealed altogether 4 major protein bands with molecular
      weights of 44-67 kD. The 44 kD band showed the most intense reaction in an
      immunoblot using Trichinella antibodies. In contrast to the E/S-antigen, in the
      immunoblot using the same defined sera, the protein bands of somatic antigen
      caused cross reactions with non specific antibodies, which would lead to false
      positive results in the ELISA.

PMID- 7575387
TI  - [Salmonella diagnosis and expanded bacteriologic differential diagnosis using
      Rambach agar].
AB  - The present study gives not only additional advises and ideas for the use of
      Rambach agar but also diagnostic support. Resulting from several years of
      diagnostic experience the medium can be recommended for enlarged routine
      differential-diagnosis of bacteria and also for improved Salmonella-diagnosis as
      an alternative medium (under section 35 LMBG; Untersuchung von Lebensmitteln;
      Nachweis von Salmonellen).

PMID- 7575388
TI  - [The content of Na, K, Ca, Mg, total P, Fe, Cu and Zn in different tissues and in
      the placenta of sheep fetuses and newborn lambs].
AB  - The content of sodium, potassium, calcium, magnesium, total-P, iron, copper, zinc
      in several tissues of sheep-fetuses (age: 92 and 120 days) as well as that of new
      born lambs was analysed. There are many changes in the chemical composition of
      the tissues, that are of functional significance.

PMID- 7575389
TI  - [Result of a European-wide inquiry about the use of artificial UV radiation
      sources in zoo animal husbandry with special regard to the mammals
      (Primates/Simiae/monkeys)].
AB  - The geographical origin of many exotic animals are areas with intensive solar
      radiation. When brought into European zoological gardens, they might suffer under
      a deficiency of UV-radiation, especially in industrial areas with an high level
      of air pollution. 100 zoological gardens in middle and northern Europe were asked
      for information, whether artificial UV-sources are used in keeping animals or
      not; 57% answered: in 60% of the cases artificial UV-sources are used, in 40%
      not. The result of using artificial UV-sources in keeping reptiles will be
      published soon. This publication shows the use of artificial UV-sources for
      mammalians, with attention to Old World nonhuman primates and especially to New
      World nonhuman primates: this species cannot utilize vitamin D2 and so requires
      D3. Additionally to an adequate nutritional diet, the exposition is done whether
      as therapeutical treatment of metabolic bone diseases, or e.g. to rise the
      vitality and the fitness. The lamp type and the chosen exposure dates are very
      different; mostly chosen with one's own judgement. To assess the safe dose,
      having positive effects, i.g. the vitamin D-synthesis and avoiding any (skin
      )damaging, the knowledge of many facts is requested: the comparison of the
      climatic conditions, albedo, the behaviour of the animals in sun, the conditions
      of keeping in zoo (cage/outdoor enclosure), influence on the appearance of the
      animals haircoat and skin (transmission rate for UV-radiation, pigmentation of
      skin a.o.) and the relation between dose and biological effect. Additionally the
      spectral distribution and the irradiance of artificial UV-sources has to be
      known. Further experimental work is necessary.

PMID- 7575390
TI  - Nucleotide diversity of mitochondrial DNAs between the swamp and the river types
      of domestic water buffaloes, Bubalus bubalis, based on restriction endonuclease
      cleavage patterns.
AB  - Cleavage patterns of mitochondrial DNAs (mtDNAs) by 15 restriction endonucleases
      were analyzed for 10 swamp and 13 river types of domestic water buffaloes.
      Digestions with nine enzymes exhibited polymorphisms giving two or three kinds of
      cleavage patterns. Five mtDNA types were identified, three types in the swamp
      buffaloes of the Philippines, Vietnam, and Indonesia (S-types) and two types in
      the river buffaloes of Bangladesh and Pakistan (R-types). Nucleotide diversities
      ranged from 0.2 to 0.6% within the S- and R-types and from 1.9 to 2.4% between
      the R-types and the S-types. These values indicated that R-type and S-type mtDNAs
      differentiated at the subspecific level of other mammalian species reported. The
      possibility of polyphyletic domestication in different places is discussed for
      the origin of two distinct types of domestic water buffaloes.

PMID- 7575391
TI  - Physiological genetics of the response to a high-sucrose diet by Drosophila
      melanogaster.
AB  - A diet medium containing 10% (w/v) sucrose can be inferred to be stressful to
      Drosophila melanogaster from the increased developmental time and reduced size
      and fecundity of emerging flies. The metabolic basis for this stress and the
      genetic response to it are of interest from the point of view of both metabolic
      regulation and the evolutionary genetics of adaptation to stress. Here the
      effects of a high-sucrose diet on live weight, total protein, stored lipid and
      glycogen, and crude activities of 12 enzymes involved in energy metabolism were
      quantified. Assays were done on a large population of Drosophila that had been
      acclimated to the laboratory. A collection of eggs was divided to produce two
      replicate populations maintained on standard medium and two replicates maintained
      on high-sucrose medium for 133 generations. At the end of this period, both
      control and sucrose-selected populations were tested on standard and on high
      sucrose medium. Results showed that the immediate effect of the high-sucrose diet
      (compared to standard medium) for both populations was a reduction in live weight
      and total protein, and activities of many of the enzymes were also reduced by the
      sucrose treatment, even after adjusting for the weight effect. Selection resulted
      in several changes on both the standard and the sucrose medium, but the direction
      of change was not always the same as the acute effect. In no case was there a
      significant medium by selection-treatment interaction. The pattern of phenotypic
      correlations did not resolve the reasons for the direction of the genetic
      responses. Correlations were generally stable across diets and after selection,
      but there were notable exceptions.

PMID- 7575392
TI  - Inheritance of allozyme loci in Bombina: one linkage group established.
AB  - Two hybridizing European species of fire-bellied toads, Bombina bombina and B.
      variegata, have alternate electromorphs fixed at a number of allozyme loci.
      Segregation of alleles at seven allozyme loci (Ldh-1, Mdh-1, Ak, Ck, Gpi, Np, and
      Est-beta) was studied in a backross progeny of an F1 interspecific hybrid male
      and a B. bombina female. Mendelian inheritance of allozyme forms at all seven
      loci was ascertained. Except for two loci, Gpi and Est-beta, which were found to
      be tightly linked (1 cM apart), other loci showed independent segregation.

PMID- 7575394
TI  - Polymorphism of blood plasma esterases in geese of the Anser genus (Aves:
      Anseriformes).

PMID- 7575393
TI  - Evolutionary origin of expandable G-C-rich triplet repeat DNA sequences.
AB  - A model explaining properties exhibited by fragile-X DNA systems arises from
      observations that time-dependent base substitutions are expressed at G-C sites
      but not at A-T sites (Biochem. Genet. 32:383, 1994). [CGG]n sequences are
      classified as most sensitive to evolutionary base substitution processes
      involving time-dependent populating of G-C sites with enol-imine states having
      enhanced stability. Increased density of these states in oocyte DNA would
      introduce a ground-state collapse double-helix of reduced energy that would
      inhibit strand separation by the replicase. Evolutionarily altered G' in CG'G
      triplets allows CG'G to be transcribed as CTG, an initiation codon. And this will
      cause reinitiation of DNA synthesis, thereby adding additional CGG units to the
      collapsed double helix. This situation would not occur in slower-evolving male
      haploid DNA that replicates frequently.

PMID- 7575395
TI  - Identification of a 130-kDa albumin in tuatara (Sphenodon) and detection of a
      novel albumin polymorphism.
AB  - Electrophoretic, immunochemical, and protein sequence analyses were performed on
      plasma albumin of the tuatara (Sphenodon), a rare reptile endemic to New Zealand.
      The analyses revealed that, unlike other terrestrial vertebrates, tuatara do not
      seem to possess a 60- to 75-kDa plasma albumin. The common form of plasma albumin
      in this genus has an apparent molecular mass of 130 kDa, making it by far the
      largest albumin reported for any terrestrial vertebrate. Starch gel
      electrophoresis of samples from tuatara on 24 of the 30 islands inhabited by this
      genus resolved two forms of the 130-kDa albumin (albumins A and C). A third
      albumin of approximately 170 kDa (albumin B), reflecting a novel alloalbuminemia,
      was found in tuatara in three geographically isolated populations. Albumin A
      appears to be restricted to populations at the southern extremity of the
      tuatara's distribution, while albumin C was found in all but four (southern)
      populations. Possible explanations for the origin and distribution of these
      albumins are discussed.

PMID- 7575396
TI  - Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi.
AB  - The use of digitonin to permeabilize the plasma membrane of Trypanosoma cruzi
      allowed the identification of a non-mitochondrial nigericin- or bafilomycin A1
      sensitive Ca(2+)-uptake mechanism. Proton uptake, as detected by ATP-dependent
      Acridine Orange accumulation, was also demonstrated in these permeabilized cells.
      Under these conditions Acridine Orange was concentrated in abundant cytoplasmic
      round vacuoles. This latter process was inhibited (and reversed) by bafilomycin
      A1, nigericin and NH4Cl in different stages of T. cruzi. Ca2+ released Acridine
      Orange from permeabilized cells, suggesting that the dye and Ca2+ were being
      accumulated in the same acidic compartment and that Ca2+ was taken up in exchange
      for protons. Addition of bafilomycin A1 (5 microM), nigericin (1 microM) or
      carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP; 1 microM) to fura 2
      loaded epimastigotes increased their intracellular Ca2+ concentration ([Ca2+]i).
      Although this effect was more noticeable in the presence of extracellular Ca2+,
      it was also observed in its absence. Addition of NH4Cl (10-40 mM) to different
      stages of T. cruzi, in the nominal absence of extracellular Ca2+ to preclude Ca2+
      entry, increased both [Ca2+]i in fura 2-loaded cells, and intracellular pH (pHi)
      in 2',7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein acetoxymethyl ester
      (BCECF)-loaded cells. Treatment of the cells with the Ca2+ ionophore ionomycin
      under similar conditions (nominal absence of extracellular Ca2+) resulted in an
      increase in [Ca2+]i and a significantly higher increase in [Ca2+]i after addition
      of NH4Cl, nigericin or bafilomycin A1, all agents which increase the pH of acidic
      compartments and make ionomycin more effective as a Ca(2+)-releasing ionophore.
      Similar results were obtained when the order of additions was reversed. Taking
      into account the relative importance of the ionomycin-releasable and the
      ionomycin plus NH4Cl-releasable Ca2+ pools, it is apparent that most of the Ca2+
      stored in different stages of T. cruzi is present in the acidic compartment thus
      identified. Taken together, these results are consistent with the presence of a
      Ca2+/H+ exchange system in an acidic vacuole, which we have named the
      'acidocalcisome' and which appears to be a unique organelle present in
      trypanosomatids.

PMID- 7575397
TI  - Endothelin-induced changes in intracellular pH and Ca2+ in coronary smooth
      muscle: role of Na(+)-H+ exchange.
AB  - The relationship between endothelin-1 (ET-1)-induced stimulation of Na(+)-H+
      exchange and intracellular free Ca2+ ([Ca2+]i) was examined in primary cultures
      of porcine coronary artery smooth muscle cells. Intracellular pH (pHi) and
      [Ca2+]i were measured using 2,7-bis-carboxyethyl-5(6)-carboxyfluorescein and the
      acetoxymethyl ester of fura-2 respectively. In HCO3(-)-free buffer (pH = 7.4), ET
      1 (0.1-50 nM) induced a sustained, dose-dependent increase in pHi. ET-1 (10 nM)
      increased pHi from 6.83 +/- 0.01 to 6.93 +/- 0.02 (P < 0.01). The alkalinization
      was blocked by the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N-isopropyl)amiloride
      (EIPA, 3 microM) or by substitution of Na+ with N-methylglucamine or choline
      chloride (P < 0.05). Recovery of pHi in response to acidification, induced by
      washout of a 20 mM NH4Cl prepulse, was > 90% inhibited by EIPA (3 microM),
      confirming the presence of an ET-1-responsive Na(+)-H+ exchanger. Coronary smooth
      muscle cells responded to ET-1 with a dose-dependent, biphasic increase in
      [Ca2+]i which was not inhibited by manipulations (EIPA pretreatment or Na(+)-free
      media) shown to block the Na(+)-H+ exchanger. The ET-1-mediated alkalinization
      was not inhibited by removal of extracellular Ca2+ ([Ca2+]o). However, complete
      blockade of the ET-1-mediated [Ca2+]i response using the intracellular Ca(2+)
      chelator, [bis-(2-amino-5-methylphenoxy)ethane-NNN'N'-tetraacetic acid
      tetraacetoxymethyl ester] (MAPTAM), in [Ca2+]o-free media, demonstrated that an
      increment in [Ca2+]i is required for activation of the Na(+)-H+ exchanger by ET
      1. The ET-1-induced rise in [Ca2+]i was not associated with a rise in pHi in the
      presence of CO2/HCO3-. We conclude that: (1) activation of Na(+)-H+ exchange by
      ET-1 requires an increment in [Ca2+]i; and (2) ET-1 stimulates EIPA-sensitive
      Na(+)-H+ exchange, but this stimulation does not modulate ET-1-induced changes in
      [Ca2+]i.

PMID- 7575398
TI  - The role of palmitoylation of the guanine nucleotide binding protein G11 alpha in
      defining interaction with the plasma membrane.
AB  - Mutations of Cys-9 to serine, Cys-10 to serine and a combination of both
      alterations were produced in a cDNA encoding murine G11 alpha to potentially
      interfere with the ability of the expressed polypeptides to act as substrates for
      post-translational palmitoylation. Each of these mutants and the wild-type
      protein were expressed in simian COS-1 cells. Mutation of either cysteine-9 or
      cysteine-10 decreased the degree of palmitoylation of the protein by some 80%
      compared with the wild-type, while the double mutant totally failed to
      incorporate [3H]palmitate. By contrast, in all transfections the endogenously
      expressed simian G11 alpha incorporated [3H]palmitate to similar levels.
      Particulate and cytoplasmic fractions from these cells were subjected to SDS/PAGE
      under conditions which allow resolution of primate and rodent forms of G11 alpha.
      Immunoblotting of these fractions demonstrated that in all cases the endogenously
      expressed simian G11 alpha was exclusively associated with the particulate
      fraction, as was the transfected and expressed wild-type murine G11 alpha. By
      contrast, each of the mutated forms of murine G11 alpha displayed a distribution
      in which approx. 70% of the expressed protein was present in the particulate
      fraction and 30% in the supernatant. To examine the conformation of the
      particulate expressed forms of murine G11 alpha, these fractions were treated
      with various concentrations of sodium cholate and immunoblots were subsequently
      performed on the solubilized and remaining particulate proteins. Whereas
      essentially all of the endogenous simian G11 alpha was solubilized by treatment
      with 1% (w/v) sodium cholate and some 50% with 0.32% cholate, expressed wild-type
      murine G11 alpha was more recalcitrant to solubilization. However, that fraction
      of wild-type murine G11 alpha which was solubilized behaved identically to the
      endogenous simian G11 alpha on Superose-12 gel-exclusion chromatography. The
      particulate fraction of the C9S/C10S double mutant of murine G11 alpha was highly
      resistant to solubilization by sodium cholate, whereas the particulate fractions
      of the two single cysteine to serine mutants were intermediate to the wild-type
      and double mutant in their ability to be solubilized by this detergent. These
      data demonstrate that the palmitoylation status of the cysteine residues at
      positions 9 and 10 in murine G11 alpha plays a central role in defining membrane
      association of this G-protein and indicate that much of the particulate fraction
      of the expressed palmitoylation-resistant mutants is likely to represent non
      functional rather than correctly folded protein.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7575399
TI  - Kinetic properties of D-fructose-1,6-bisphosphate 1-phosphohydrolase isolated
      from human muscle.
AB  - D-Fructose-1,6-bisphosphate 1-phosphohydrolase (EC 3.1.3.11) [Fru(1,6)Pase] was
      isolated from human muscle in an electrophoretically homogeneous form, free of
      aldolase contamination. The enzyme is inhibited by the substrate [fructose (1,6)
      bisphosphate]. Km is 0.77 microM; Kis is 90 microM. The fructose-2,6-bisphosphate
      [Fru(2,6)P2], a regulator of gluconeogenesis, inhibits human muscle Fru(1,6)Pase
      with Ki = 0.13 microM. To determine Km, Kis and Ki the integrated method was
      used. AMP is an allosteric inhibitor of Fru(1,6)Pase. As with other mammalian
      isoenzymes, the human muscle enzyme is more strongly inhibited by AMP than is the
      liver isoenzyme [Dzugaj and Kochman (1980) Biochim. Biophys. Acta 614, 407-412].
      Both of the inhibitors [AMP and Fru(2,6)P2] act synergistically on human muscle
      Fru(1,6)Pase. Ki for Fru(2,6)P2 determined in the presence of 0.4 microM AMP was
      0.028 microM. The human muscle enzyme, like other mammalian Fru(1,6)Pases,
      requires Mg2+ for its activity. The Ka for magnesium was 232 microM, and h (Hill
      coefficient) = 2.0.

PMID- 7575400
TI  - Cloning and analysis of the promoter region of the rat SM22 alpha gene.
AB  - We have cloned and sequenced a 1.9 kb fragment of the 5'-upstream sequence of the
      smooth-muscle-specific gene SM22 alpha. The region cloned consisted of the SM22
      alpha promoter, a 65 bp exon containing most of the 5'-untranslated region and
      307 bp of the first intron. A 1.5 kb fragment at the 5' end of this sequence was
      able to drive the expression of a reporter chloramphenicol acetyltransferase
      (CAT) gene in both vascular smooth-muscle cells and Rat-1 fibroblasts. This
      promoter region did not contain a consensus TATAA box but contained the sequence
      TTTAAA 25 bp from the major start site identified by primer extension. Deletion
      analysis showed that a fragment of the promoter from +65 to -303 was more active
      in both cell types than the 1.5 kb fragment suggesting that there are silencer
      sequences in the region 5' to the core promoter. CAT activity was also observed
      with fragments containing bases +65 to -193 and +65 to -117 in smooth-muscle
      cells. In contrast with the smooth-muscle cells, no CAT activity was detected in
      Rat-1 fibroblasts with the smallest two fragments. The residual promoter activity
      in the smallest fragment of the SM22 alpha promoter tested suggested that, unlike
      the smooth-muscle alpha-actin promoter, transcription from the SM22 alpha
      promoter can occur in smooth-muscle cells in the absence of factors binding to
      CC(A/Trich)6GG (CArG box) or CANNTG (E box) motifs.

PMID- 7575401
TI  - Biochemical changes in the collagenous matrix of osteoporotic avian bone.
AB  - No detailed biochemical analysis has been carried out of the compositional
      changes in the collagen matrix of avian bone in relation to increased bone
      fragility in osteoporosis. We have shown that osteoporosis in avian bone is
      certainly not just a simple loss of apatite and collagen, but involves
      significant changes in the biochemistry of the collagen molecule and consequently
      in the physical properties of the fibre. The decreased mechanical strength and
      the change in the thermal stability can be directly related to changes in post
      translational modifications, i.e. lysine hydroxylation and the intermolecular
      cross-link profile. The increased hydroxylation and change in cross-linking are
      consistent with increased turnover of the collagen, possibly in an attempt to
      initiate a repair mechanism which, in fact, leads to an acceleration in the
      increase in fragility of the bone. Clearly there are post-translational
      modifications of the newly synthesized collagen in avian osteoporosis, and these
      changes may play a role in the pathogenesis of the disease.

PMID- 7575402
TI  - Unpredictable behaviour of mucins in SDS/polyacrylamide-gel electrophoresis.

PMID- 7575404
TI  - Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1
      and its association with phosphatidylinositol 3-kinase in rat heart.
AB  - We have investigated whether angiotensin II (AII) is able to induce insulin
      receptor substrate 1 (IRS-1) phosphorylation and its association with
      phosphatidylinositol 3-kinase (PI 3-kinase) in the rat heart in vivo. The
      phosphorylation state of IRS-1 following infusion of insulin or AII via the vena
      cava was assessed after immunoprecipitation with an anti-peptide antibody to IRS
      1 followed by immunoblotting with an anti-phosphotyrosine antibody and an anti-PI
      3-kinase antibody. Densitometry indicated a 5.6 +/- 1.3-fold increase in IRS-1
      phosphorylation after stimulation with AII and a 12.8 +/- 3.1-fold increase after
      insulin. The effect was maximal at an AII concentration of 10(-8) M and occurred
      1 min after infusion. There was also a 6.1 +/- 1.2-fold increase in IRS-1
      associated PI 3-kinase in response to AII. In the isolated perfused heart the
      result was similar, showing a direct effect of AII on this pathway. When the
      animals were pretreated for 1 h with DuP 753, a non-peptide AII-receptor 1 (AT1
      receptor) antagonist, there was a marked reduction in the AII-induced tyrosine
      phosphorylation of IRS-1, suggesting that phosphorylation is initially mediated
      by the AT1 receptor. We conclude that AII stimulates tyrosine phosphorylation of
      IRS-1 and its association with PI 3-kinase. This pathway thus represents an
      additional signalling mechanism stimulated by AII in the rat heart in vivo.

PMID- 7575403
TI  - Kinetic models in reverse micelles.

PMID- 7575405
TI  - Nitric oxide rapidly scavenges tyrosine and tryptophan radicals.
AB  - By utilizing a pulse-radiolytic technique, we demonstrate for the first time that
      the rate constant for the reaction of nitric oxide (.NO) with biologically
      relevant tyrosine and tryptophan radicals (Tyr. and Trp. respectively) in amino
      acids, peptides and proteins is of the order of (1-2) x 10(9) M-1.s-1. We also
      show that .NO effectively interferes with electron-transfer processes between
      tryptophan and tyrosine residues in proteins subjected to pulse radiolysis. The
      near diffusion-controlled rates of these reactions, coupled with the increasingly
      recognized role of protein radicals in enzyme catalysis and oxidative damage,
      suggest that Tyr. and Trp. are likely and important targets for .NO generated in
      vivo.

PMID- 7575406
TI  - Lipopolysaccharide-induced interleukin-8 gene expression in human granulocytes:
      transcriptional inhibition by interferon-gamma.
AB  - We recently showed that lipopolysaccharide (LPS) is a potent inducer of
      interleukin-8 (IL-8) expression in human polymorphonuclear leucocytes (PMN), at
      the level of both mRNA and protein, and that interferon-gamma (IFN gamma)
      inhibits IL-8 mRNA accumulation in stimulated PMN. To further define the
      molecular basis of the regulation of IL-8 gene expression in PMN, we investigated
      the effects of LPS and IFN gamma at both the transcriptional and post
      transcriptional levels. As determined by Northern blot analysis, new protein
      synthesis was not required for the induction of IL-8 mRNA expression by LPS.
      Neither did the half-life of IL-8 mRNA in LPS-treated PMN differ from that
      observed in untreated cells. However, nuclear run-on analysis revealed that LPS
      increased the transcription of the IL-8 and IL-1 beta genes and that, in LPS
      activated cells, IFN gamma markedly inhibited the rate of IL-8 gene
      transcription, but not that of IL-1 beta. IFN gamma did not affect IL-8 mRNA
      stability in LPS-treated PMN, indicating that the cytokine does not regulate LPS
      induced IL-8 gene expression through post-transcriptional events. These results
      provide the first evidence that human granulocytes can actively transcribe the IL
      8 gene, and that transcriptional inhibition is the mechanism by which IFN gamma
      inhibits IL-8 gene expression in PMN.

PMID- 7575407
TI  - Structure and tissue-specific expression of the Drosophila melanogaster
      organellar-type Ca(2+)-ATPase gene.
AB  - A 14 kb genomic clone covering the organellar-type Ca(2+)-ATPase gene of
      Drosophila melanogaster has been isolated and characterized. The sequence of a
      7132 bp region extending from 1.1 kb 5' upstream of the initiation ATG codon over
      the polyadenylation signal at the 3' end has been determined. The gene consists
      of nine exons including one with an exceptional size of 2172 bp representing 72%
      of the protein coding region. Introns are relatively small (< 100 bp) except for
      the 3' intron which has a size of 2239 bp, an exceptionally large size among
      Drosophila introns. Five of the introns are in the same positions in Drosophila,
      Artemia and rabbit SERCA1 Ca(2+)-ATPase genes. There is only one organellar-type
      Ca(2+)-ATPase gene in the Drosophila genome, as was shown by Southern-blot
      analysis [Varadi, Gilmore-Hebert and Benz (1989) FEBS Lett. 258, 203-207] and by
      chromosomal localization [Magyar and Varadi (1990) Biochem. Biophys. Res. Commun.
      173, 872-877]. Primer extension and S1-nuclease assays revealed a potential
      transcription initiation site 876 bp upstream of the translation initiation ATG
      with a TATA-box 23 bp upstream of this site. Analysis of the 5' region of the
      Drosophila organellar-type Ca(2+)-ATPase gene suggests the presence of potential
      recognition sequences of various muscle-specific transcription factors and shows
      a region with remarkable similarity to that in the rabbit SERCA2 gene. The tissue
      distribution of expression of the organellar-type Ca(2+)-ATPase gene has been
      studied by in situ RNA-RNA hybridization on microscopic sections. A low mRNA
      abundance can be detected in each tissue of adult flies, suggesting a
      housekeeping function for the gene. On the other hand a pronounced tissue
      specificity of expression has also been found as the organellar-type Ca(2+)
      ATPase is expressed at a very high level in cell bodies of the central nervous
      system and in various muscles.

PMID- 7575408
TI  - Covalent modification of engineered cysteines in the nicotinic acetylcholine
      receptor agonist-binding domain inhibits receptor activation.
AB  - We constructed and characterized a series of nicotinic receptor mutants with a
      cysteine substituted for one of the amino acid residues in the alpha-subunit
      between positions 183 and 198. This region of the receptor is known to
      participate in agonist binding and channel activation. The goal of this 'cysteine
      scanning mutagenesis' is to introduce the reactivity of a free thiol group into
      functionally important protein domains; modification of the introduced cysteines
      can then be used to probe the structure and function of the targeted region.
      Mutants were examined by coexpression with the beta-, gamma- and delta-subunits
      in Xenopus oocytes using two-microelectrode voltage clamp recording. Twelve of
      fourteen mutants expressed receptors with properties comparable with the wild
      type, including sensitivity to reduction by dithiothreitol (DTT). This indicates
      that introduction of an additional cysteine within this region of the receptor
      did not interfere with formation of the native disulphide between alpha Cys-192
      and alpha Cys-193. Only one mutation, alpha Y198C, caused dramatic changes in the
      EC50 for acetylcholine (ACh) and in the sensitivity to DTT. We then examined the
      effects of the thiol modification and found two mutants, alpha H186C and alpha
      V188C, that showed significant decreases in responsiveness to ACh after exposure
      to methylmethanethiosulphonate (MMTS). Dose-response measurements show that
      exposure of alpha H186C mutants to MMTS causes a shift in apparent agonist
      affinity without changing the peak response, and this is not reversible by DTT.
      In contrast, the MMTS-treated alpha V188C mutants show changes in both apparent
      affinity and peak response which are readily reversed by DTT. Together, our data
      show that these two nearby residues occupy markedly different environments
      relative to the contact points for ACh. They also demonstrate that cysteine
      substitution mutagenesis can be successfully applied to protein domains that
      include functionally important disulphides.

PMID- 7575409
TI  - Differentiation of rat brown adipocytes during late foetal development: role of
      insulin-like growth factor I.
AB  - Rat brown adipocytes at day 22 of foetal development showed greater size, higher
      mitochondria content and larger amounts of lipids, as determined by flow
      cytometry, than 20-day foetal cells. Simultaneously, an inhibition on the
      percentage of brown adipocytes into S+G2/M phases of the cell cycle was observed
      between days 20 and 22 of foetal development. The expression of several
      adipogenesis-related genes, such as fatty acid synthase, malic enzyme, glucose-6
      phosphate dehydrogenase and insulin-regulated glucose transporter, increased at
      the end of foetal life in brown adipose tissue. In addition, the lipogenic enzyme
      activities and the lipogenic flux increased during late foetal development,
      resulting in mature brown adipocytes showing a multilocular fat droplet
      phenotype. Concurrently, brown adipocytes induced the expression of the
      uncoupling protein (UP) mRNA and UP protein, as visualized by immunofluorescence.
      The three isoforms of CCAAT enhancer-binding proteins (C/EBPs) were expressed at
      the mRNA level in brown adipose tissue at day 20. C/EBP alpha decreased and C/EBP
      beta and delta increased their expression between days 20 and 22 of foetal
      development, respectively. Brown adipose tissue constitutively expressed insulin
      like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) mRNAs. Moreover, IGF-IR
      mRNA content increased between days 20 and 22 in parallel with the occurrence of
      tissue differentiation.

PMID- 7575410
TI  - Characterization of the endopeptidase PC2 activity towards secretogranin II in
      stably transfected PC12 cells.
AB  - To study the processing of secretogranin II (SgII) by the prohormone convertase
      PC2 we have generated a stable PC12 cell line which expresses mouse PC2. We here
      present the characteristics of the PC12/PC2 cell line and demonstrate that the
      exogenous PC2 is sorted and stored in secretory granules in the PC12/PC2 cell
      line as efficiently as the endogenous granins. By indirect immunofluorescence
      with antibodies specific for chromogranin B (CgB) and PC2 we were able to
      establish that the PC2 is stored in secretory granules in the PC12/PC2 cell line.
      After subcellular fractionation, followed by immunoblotting, the mature 68 kDa
      form of PC2 was found co-sedimented with SgII in fractions containing secretory
      granules. Two-dimensional gel electrophoresis was used to characterize a
      secretory granule fraction obtained from the PC12/PC2 cells, and a comparison was
      done of the electrophoretic pattern obtained from the PC12/PC2 cells with the
      parent cell line PC12. The products derived from the processing of SgII by PC2
      were identified by immunoblotting with a panel of antibodies directed against
      SgII. Using [35S]sulphate to label the newly synthesized SgII, we performed a
      time course to monitor the appearance of the lower-molecular-mass fragments of
      SgII: beginning 15 min after a 5 min pulse of [35S]sulphate we were able to
      detect the first proteolytic fragment of SgII. Our results demonstrate that SgII
      is proteolytically processed by PC2 in the immature secretory granule into
      several lower-molecular-mass proteins, the major ones being an 18 kDa sulphated
      fragment and a 28 kDa fragment.

PMID- 7575411
TI  - Ca2+ storage in Trypanosoma brucei: the influence of cytoplasmic pH and
      importance of vacuolar acidity.
AB  - The hypothesis that changes in cytosolic pH effect the release from intracellular
      compartments of stored calcium in Trypanosoma brucei was addressed by the use of
      procyclic and bloodstream trypomastigotes of T. brucei loaded with the
      fluorescent reagents 2',7'-bis-(2-carboxyethyl)-5(and 6)-carboxyfluorescein
      (BCECF) to measure intracellular pH (pHi), or fura 2 to measure intracellular
      free calcium ([Ca2+]i). Experiments were performed in EGTA-containing buffers, so
      increases in [Ca2+]i reflected release of stored calcium rather than Ca2+ entry.
      Nigericin reduced pHi and increased [Ca2+]i in loaded cells, whilst propionate
      reduced pHi, but did not affect [Ca2+]i, and NH4Cl increased both variables, so
      there appears to be no correlation between pHi and [Ca2+]i. Treatment of the
      cells with the calcium ionophore ionomycin under similar conditions (nominal
      absence of extracellular Ca2+) resulted in an increase of [Ca2+]i which was
      greatly increased by addition of either NH4Cl, nigericin or the vacuolar H(+)
      ATPase inhibitor bafilomycin A1. Similar results were obtained when the order of
      additions was reversed or when digitonin-permeabilized cells were used with the
      Ca2+ indicator arsenazo III. The results suggest that more Ca2+ is stored in this
      acidic compartment in procyclic than in bloodstream forms. Taking into account
      the relative importance of the ionomycin-releasable and the ionomycin-plus-NH4Cl
      releasable Ca2+ pools, it is apparent that a significant amount of the Ca2+
      stored in T. brucei trypomastigotes is present in the acidic compartment thus
      identified.

PMID- 7575412
TI  - Early signalling events implicated in leukotriene B4-induced activation of the
      NADPH oxidase in eosinophils: role of Ca2+, protein kinase C and phospholipases C
      and D.
AB  - The early signalling events that may ultimately contribute to the assembly and
      subsequent activation of the NADPH oxidase in guinea-pig peritoneal eosinophils
      were investigated in response to leukotriene B4 (LTB4). LTB4 promoted a rapid,
      transient and receptor-mediated increase in the rate of H2O2 generation that was
      potentiated by R 59 022, a diradylglycerol (DRG) kinase inhibitor, implicating
      protein kinase C (PKC) in the genesis of this response. This conclusion was
      supported by the finding that the PKC inhibitor, Ro 31-8220, attenuated (by about
      30%) the peak rate of LTB4-induced H2O2 generation under conditions where the
      same response evoked by 4 beta-phorbol 12,13-dibutyrate (PDBu) was inhibited by
      more than 90%. Paradoxically, Ro 31-8220 doubled the amount of H2O2 produced by
      LTB4 which may relate to the ability of PKC to inhibit cell signalling through
      phospholipase C (PLC). Indeed, Ro 31-8220 significantly enhanced LTB4-induced
      Ins(1,4,5)P3 accumulation and the duration of the Ca2+ transient in eosinophils.
      Experiments designed to assess the relative importance of DRG-mobilizing
      phospholipases in LTB4-induced oxidase activation indicated that phospholipase D
      (PLD) did not play a major role. Thus, although H2O2 generation was abolished by
      butan-1-ol, this was apparently unrelated to the inhibition of PLD, as LTB4
      failed to stimulate the formation of Ptd[3H]BuOH in [3H]butan-1-ol-treated
      eosinophils. Rather, the inhibition was probably due to the ability of butan-1-ol
      to increase the eosinophil cyclic AMP content. In contrast, Ca(2+)- and PLC
      driven mechanisms were implicated in H2O2 generation, as LTB4 elevated the
      Ins(1,4,5)P3 content and intracellular free Ca2+ concentration in intact cells,
      and cochelation of extracellular and intracellular Ca2+ significantly attenuated
      LTB4-induced H2O2 generation. Pretreatment of eosinophils with wortmannin did not
      affect LTB4-induced H2O2 production at concentrations at which it abolished the
      respiratory burst evoked by formylmethionyl-leucylphenylalanine in human
      neutrophils. Collectively, these data suggest that LTB4 activates the NADPH
      oxidase in eosinophils by PLD- and PtdIns 3-kinase-independent mechanisms that
      involve Ca2+, PLC and PKC. Furthermore, the activation of additional pathways
      that do not require Ca2+ is also suggested by the finding that LTB4 evoked a
      significant respiratory burst in Ca(2+)-depleted cells.

PMID- 7575413
TI  - Structure of Leishmania lipophosphoglycan: inter- and intra-specific polymorphism
      in Old World species.
AB  - The most abundant surface macromolecule on the promastigote stage of leishmanial
      parasites is a polymorphic lipophosphoglycan (LPG). We have elucidated the
      structures of two new LPGs, from Leishmania tropica (LRC-L36) and L. aethiopica
      (LRC-L495), and investigated the nature of intra-specific polymorphism in the
      previously characterized LPG of L. major (LRC-L456 and -L580). These molecules
      contain a phosphoglycan chain, made up of repeating PO4-6Gal beta 1-4Man units
      and a conserved hexaglycosyl-phosphatidylinositol membrane anchor. Extensive
      polymorphism occurs in the extent to which the LPG repeat units are substituted
      with different glycan side chains. The L. tropica LPG is the most complex LPG
      characterized to date, as most of the repeat units are substituted with more than
      19 different glycan side chains. All of these side chains, including the novel
      major glycans, Arap beta 1-3Glc beta 1- and +/- Arap beta 1-2Glc beta 1-4[+/-
      Arap beta 1-2]Glc beta 1-, are linked to the C-3 position of the backbone
      disaccharide galactose. In contrast, the L. aethiopica LPG repeat units are
      partially substituted (35%) with single alpha-mannose residues that are linked,
      unusually, to the C-2 position of the mannose in the backbone disaccharide.
      Polymorphism is also evident in the spectrum of alpha-mannose-containing
      oligosaccharides that cap the non-reducing terminus of the phosphoglycan chains
      of these LPGs. Finally, analysis of the L. major LPGs showed that, while some
      strains contain LPGs which are highly substituted with side chains of beta Gal,
      Gal beta 1-3Gal beta 1- and Arap beta 1-2Gal beta 1-3Gal beta 1-, the LPGs of
      other strains (i.e L. major LRC-L456) are essentially unsubstituted. Recent
      studies have shown that the LPG side chains and cap structures can mediate
      promastigote attachment to a number of different receptors along the midgut of
      the sandfly vector. The possible significance of LPG polymorphism on the ability
      of these parasites to infect a number of different sandfly vectors is discussed.

PMID- 7575414
TI  - Effects of fasting on hepatic and peripheral glucose metabolism in conscious rats
      with near-total fat depletion.
AB  - Experimental diabetes and fasting are both associated with hypoinsulinaemia and
      share several other metabolic features. We investigated hepatic and peripheral
      glucose metabolism in young rats after near-total depletion of their fat mass.
      Conscious rats were fasted for 72 h (n = 13), while 6 h-fasted animals (n = 14)
      served as controls. Rats were studied either during saline infusion or insulin
      (18 m-units/kg per min)-clamp studies. In fasting, despite a 2-fold increase in
      hepatic glucose-6-phosphatase (Glc-6-Pase) Vmax. (from 16 +/- 2 mumol/g of liver
      per min in control; P < 0.001), the basal hepatic glucose production (HGP)
      decreased by 47% [from 88 +/- 3 mumol/kg lean body mass (LBM) per min in control;
      P < 0.01]. The decreased HGP in fasting was associated with a 70% decrease in the
      hepatic levels of glucose 6-phosphate (Glc-6-P) (from 366 +/- 53 nmol/g wet wt.
      in control; P < 0.01). Thus Glc-6-Pase activity assayed in the presence of the
      Glc-6-P levels found in vivo was decreased by 44%. During hyperinsulinaemia,
      peripheral glucose uptake was decreased by 15% with 3 days of fasting (from 272
      +/- 17 mumol/kg LBM per min in control; P < 0.01). This was completely accounted
      for by a 42% decrease in whole-body glycolysis (P < 0.01), while the rate of
      glycogen synthesis was unchanged. Thus fasting (after near-total fat depletion)
      differs from experimental diabetes because: (1) despite markedly increased Glc-6
      Pase, HGP is decreased in fasting, due to a marked decrease in the substrate
      level (Glc-6-P) in vivo; and (2) the impairment in peripheral insulin sensitivity
      in fasting is due to a decrease in the glycolytic, and not the glycogen
      synthetic, pathway.

PMID- 7575415
TI  - Pro-oxidant effects of cross-linked haemoglobins explored using liposome and
      cytochrome c oxidase vesicle model membranes.
AB  - The therapeutic use of cell-free haemoglobin as a blood substitute has been
      hampered by toxicological effects. A model asolectin
      (phosphatidylcholine/phosphatidylethanolamine) liposome system was utilized to
      study the pro-oxidant efficiency of several chemically modified haemoglobins on
      biological membranes. Lipid peroxidation, resulting from the interactions between
      haemoglobin and liposomes, was measured by conjugated diene formation and the
      maximal rates of oxygen uptake. Spectral changes gave insight into the occurrence
      of the ferryl iron species. The residual reactivity of oxidatively damaged
      haemoglobins with ligands during incubation with liposomes was assessed from
      rapid kinetic carbon monoxide-binding experiments. Liposomes in which cytochrome
      c oxidase was embedded show both haemoglobin and the enzyme to be oxidatively
      damaged during incubation. The functional state of cytochrome c oxidase was
      monitored in the presence and absence of a free radical scavenger. Once in
      contact, both unmodified and modified haemoglobins triggered and maintained
      severe radical-mediated membrane damage. Differences in the pro-oxidant
      activities among haemoglobins may be explained by either the differential
      population of their ferryl intermediates or disparate dimerization and transfer
      of haem into the membrane with subsequent haem degradation. This study may
      contribute to a better understanding of the molecular determinants of haemoglobin
      interactions with a variety of biological membranes.

PMID- 7575416
TI  - Identification of a brain-specific protein kinase C zeta pseudogene (psi PKC
      zeta) transcript.
AB  - Protein kinase C (PKC), a widely-distributed enzyme implicated in the regulation
      of many physiological processes, consists of a family of at least twelve
      isoenzymes which differ in tissue distribution, subcellular localization,
      regulatory properties, etc. In addition to this heterogeneity at the protein
      level, we identify here for the first time a PKC zeta pseudogene (psi PKC zeta)
      transcript, specifically expressed in the brain, which is identical with PKC zeta
      except for sequence divergence within the first variable domain (V1). The
      authenticity of this unique V1 sequence (V1') in mRNA was confirmed by RNase
      protection and reverse transcriptase PCR (RT-PCR) analysis. When translated in
      frame with PKC zeta, a stop codon is located 28 amino acids towards the N
      terminus of the divergence point and the intervening sequence lacks an expected
      initiating methionine. psi PKC zeta is non-functional in terms of protein
      synthesis since Western blotting with an antibody directed against the C-terminus
      of PKC zeta failed to reveal a protein smaller than PKC zeta, and synthetic psi
      PKC zeta RNA failed to support protein synthesis in a translation system in
      vitro. PCR amplification of rat genomic DNA demonstrated lack of an intron at the
      junction between V1' and the first constant domain (the V1'-C1 border), and
      genomic DNA Southern blot analysis using PKC zeta and psi PKC zeta-specific
      probes indicated that they have different loci. psi PKC zeta, therefore, is not
      derived from the PKC zeta gene by alternative splicing, but rather is the product
      of a distinct gene. In Northern blot analysis, brain PKC zeta mRNA was identified
      as a low-abundance 3.1 kb transcript, while the abundant 2.5 and 4.7 kb mRNAs
      previously reported to encode PKC zeta are, in fact, psi PKC zeta transcripts.
      Analysis of rat brain, heart, lung, liver, kidney and skeletal muscle revealed
      psi PKC zeta mRNA only in brain. PKC zeta transcripts were most abundant in lung
      and kidney (2.7 and 4.7 kb mRNAs), correlating with the tissue profile of PKC
      zeta immunoreactivity in Western blots. Probes complementary to the common V5 and
      C1 domains detected both PKC zeta and psi PKC zeta transcripts. Interestingly,
      the C1 probe also detected an abundant novel 1.75 kb mRNA in brain and heart,
      suggesting the existence of an additional PKC zeta-related species. This work,
      therefore, also emphasizes the importance of careful choice of oligonucleotide
      and cDNA probes to study PKC zeta mRNA.

PMID- 7575417
TI  - Variations in composition of dietary fats affect hepatic uptake and metabolism of
      chylomicron remnants.
AB  - The hepatic metabolism of [1-14C]oleate- and [1,2-3H]cholesterol-dual-labelled
      chylomicron remnants derived from olive, corn, palm and fish oil and butter fat
      was compared by adding each lipoprotein separately to the perfusate of isolated
      livers from rats fed on a normal diet. Labelled remnants from butter fat and fish
      oil were removed more rapidly from the perfusate than remnants derived from
      olive, corn and palm oil. The oxidation of labelled remnant fatty acid from olive
      oil, fish oil or butter fat was four to seven times greater than that from corn
      and palm oil. Labelled fatty acid in fish oil remnants was incorporated into
      phospholipid significantly more efficiently than the labelled fatty acid in
      olive, corn or palm oil remnants, with butter fat giving an intermediate value.
      For all the remnants, there was a significant amount of hydrolysis of labelled
      esterified cholesterol by the liver which was dependent on the magnitude of
      hepatic uptake of each type of remnant. The recovery of remnant [3H]cholesterol
      label in the bile was 50% less with palm oil remnants than with all the other
      remnants studied. The results indicate that the fatty acid composition of
      chylomicron remnants has a major impact on their uptake and metabolism by the
      liver.

PMID- 7575418
TI  - Insulin regulates enzyme activity, malonyl-CoA sensitivity and mRNA abundance of
      hepatic carnitine palmitoyltransferase-I.
AB  - The regulation of hepatic mitochondrial carnitine palmitoyltransferase-I (CPT-I)
      was studied in rats during starvation and insulin-dependent diabetes and in rat
      H4IIE cells. The Vmax. for CPT-I in hepatic mitochondrial outer membranes
      isolated from starved and diabetic rats increased 2- and 3-fold respectively over
      fed control values with no change in Km values for substrates. Regulation of
      malonyl-CoA sensitivity of CPT-I in isolated mitochondrial outer membranes was
      indicated by an 8-fold increase in Ki during starvation and by a 50-fold increase
      in Ki in the diabetic state. Peroxisomal and microsomal CPT also had decreased
      sensitivity to inhibition by malonyl-CoA during starvation. CPT-I mRNA abundance
      was 7.5 times greater in livers of 48-h-starved rats and 14.6 times greater in
      livers of insulin-dependent diabetic rats compared with livers of fed rats. In
      H4IIE cells, insulin increased CPT-I sensitivity to inhibition by malonyl-CoA in
      4 h, and sensitivity continued to increase up to 24 h after insulin addition. CPT
      I mRNA levels in H4IIE cells were decreased by insulin after 4 h and continued to
      decrease so that at 24 h there was a 10-fold difference. The half-life of CPT-I
      mRNA was 4 h in the presence of actinomycin D or with actinomycin D plus insulin.
      These results suggest that insulin regulates CPT-I by inhibiting transcription of
      the CPT-I gene.

PMID- 7575419
TI  - Binding of sesquiterpene lactone inhibitors to the Ca(2+)-ATPase.
AB  - The mechanism of inhibition of the Ca(2+)-ATPase from sarcoplasmic reticulum by
      the sesquiterpene lactones thapsigargin, trilobolide and thapsivillosin A (TvA)
      has been determined. A decrease in the affinity of the ATPase for Ca2+ is
      observed in the presence of the inhibitors (I), consistent with a shift in the
      E1/E2 equilibrium for the ATPase towards E2 forms. Amounts of inhibitor beyond a
      1:1 molar ratio with ATPase produce no further decrease in affinity for Ca2+,
      inconsistent with the formation of a dead-end complex. Measurements of the rate
      of quenching of the tryptophan fluorescence of the ATPase by TvA are consistent
      with an association step to give E2I followed by an isomerization to a modified
      state E2AI. The kinetics of the reversal of the effects of TvA by Ca2+ at sub
      stoichiometric amounts of TvA are bi-exponential, with a fast component whose
      rate is independent of TvA concentration and equal to the rate observed in the
      absence of TvA, and a slow component whose rate decreases with increasing TvA
      concentration. These observations are also consistent with the formation of a
      modified state E2AI following the initial binding of I to E2. The equilibrium
      constant E2AI/E2I increases in the order TvA < trilobolide < thapsigargin. The
      results suggest that the effects of the inhibitors on the overall ratio of E2 to
      E1 forms of the ATPase follow largely from the formation of E2AI from E2I, and
      that binding constants are very similar for E1Ca2, E1 and E2.

PMID- 7575420
TI  - Sequence requirements for proinsulin processing at the B-chain/C-peptide
      junction.
AB  - Proinsulin is converted into insulin by the action of two endoproteases. Type I
      (PC1/PC3) is thought to cleave between the B-chain and the connecting peptide (C
      peptide) and type II (PC2) between the C-peptide and the A-chain. An acidic
      region immediately C-terminal to the point of cleavage at the B-chain/C-peptide
      junction is well conserved throughout evolution and has been suggested to be
      important for proinsulin conversion [Gross, Villa-Komaroff, Kahn, Weir and Halban
      (1989) J. Biol. Chem. 264, 21486-21490]. We have here compared the precise role
      of this region as a whole and just the first acidic residue C-terminal to the
      point of cleavage in processing of proinsulin by PC3. To this end, several
      mutations were introduced in this region of human proinsulin (native sequence, B
      chain RREAEDL C-peptide): RRPAEDL (C1Pro mutant); RRLAEDL (C1Leu mutant); RRL (C1
      C4del mutant); RRE (del-C1Glu mutant). Mutant and native cDNAs were stably
      transfected into AtT20 (pituitary corticotroph) cells, in which PC3 is known to
      be the major conversion endoprotease, and kinetics of proinsulin conversion were
      studied (pulse-chase/HPLC analysis of proinsulin-related peptides). The results
      show that the acidic region following the B-chain/C-peptide junction is indeed
      important for PC3 cleavage at this site, and that the reduced cleavage observed
      for the C1-C4del mutant proinsulin can be partially overcome by replacing the
      acidic region with a single acidic residue (del-C1Glu mutant). Replacing only the
      first residue of the acidic region with leucine (C1Leu mutant) has no impact on
      conversion, whereas its replacement with proline (C1Pro mutant) almost completely
      abolishes cleavage at the B-chain/C-peptide junction without affecting that at
      the C-peptide/A-chain junction.

PMID- 7575421
TI  - Effects of phospholipid fatty acyl chain length on phosphorylation and
      dephosphorylation of the Ca(2+)-ATPase.
AB  - The kinetics of the Ca(2+)-ATPase purified from sarcoplasmic reticulum have been
      studied after reconstitution into bilayers of dimyristoleoylphosphatidylcholine
      [di(C14:1)PC], dioleoylphosphatidylcholine[di(C18:1)PC] and
      dinervonylphosphatidylcholine [di(C24:1)PC]. In di(C24:1)PC the rate of
      phosphorylation of the ATPase by ATP was comparable with that in di(C18:1)PC
      (about 70 s-1), but in di(C14:1)PC the rate was much lower (21 s-1). Fluorescence
      responses of the ATPase suggest changes in the phosphoryl-transfer step rather
      than in the preceding conformational change E1Ca2ATP<-->E1'Ca2ATP. The rate of
      dephosphorylation of the phosphorylated ATPase was found to decrease in the order
      di(C24:1)PC < di(C14:1)PC < di(C18:1)PC. For the ATPase in di(C24:1)PC the rate
      of dephosphorylation (3.3 s-1) was slow enough to be the rate-limiting step for
      ATP hydrolysis; in di(C14:1)PC, it is suggested that both phosphorylation and
      dephosphorylation contribute to rate limitation. Phosphorylation of the ATPase in
      di(C24:1)PC by Pi was normal, but no phosphoenzyme could be detected in
      di(C14:1)PC. The rate of the Ca(2+)-transport step was normal in di(C24:1)PC,
      suggesting that the single Ca2+ ion bound to the ATPase in di(C24:1)PC could be
      transported.

PMID- 7575422
TI  - Extracellular Ca2+ stimulates the activation of mitogen-activated protein kinase
      and cell growth in human fibroblasts.
AB  - In serum-free medium containing serum replacements but totally lacking in protein
      growth factors, diploid human fibroblasts remained quiescent if the extracellular
      Ca2+ concentration was only 0.1 mM. However, when the Ca2+ concentration in this
      medium was increased to 1 mM, the cells replicated as rapidly as they do in
      medium supplemented with protein growth factors. When quiescent cells in medium
      with only 0.1 mM Ca2+ were exposed to 1 or 10 mM Ca2+ or 100 ng/ml epidermal
      growth factor (EGF), the 42 kDa and 44 kDa forms of mitogen-activated protein
      kinase (MAPK) were rapidly activated, as demonstrated by a characteristic
      electrophoretic mobility shift of these proteins and by their enhanced ability to
      phosphorylate myelin basic protein (MBP). Analysis of fractions from Mono Q anion
      exchange chromatography of lysates of cells exposed to 10 mM Ca2+ or 100 ng/ml
      EGF revealed a peak of MBP phosphorylation activity that was coeluted with p42
      and p44 MAPK as shown by immunoblot analysis. Activation of MAPK by extracellular
      Ca2+ was dose-dependent and biphasic, with a peak of activation at 5-10 min after
      exposure, followed by a period of sustained activation of MAPK at a lower level.
      This pattern has been shown [Vouret-Craviari, Van Obberghen-Schilling, Scimeca,
      Van Obberghen and Pouyssegur (1993) Biochem J. 289, 209-214] to correlate with
      the re-entry of mammalian cells into the cell cycle.

PMID- 7575423
TI  - Mitochondrial ATP synthase subunit c stored in hereditary ceroid-lipofuscinosis
      contains trimethyl-lysine.
AB  - The subunit c protein of mitochondrial ATP synthase accumulates in lysosomal
      storage bodies of numerous tissues in human subjects with certain forms of ceroid
      lipofuscinosis, a degenerative hereditary disease. Subunit c appears to
      constitute a major fraction of the total storage-body protein. Lysosomal
      accumulation of subunit c has also been reported in putative animal models (dogs,
      sheep and mice) for ceroid-lipofuscinosis. In humans with the juvenile form of
      the disease, hydrolysates of total storage-body protein have been found to
      contain significant amounts of epsilon-N-trimethyl-lysine (TML). TML is also
      abundant in storage-body protein hydrolysates from affected dogs and sheep. These
      findings suggested that one or both of the two lysine residues of subunit c might
      be methylated in the stored form of the protein. The normal subunit c protein
      from mitochondria does not appear to be methylated. In a putative canine model
      for human juvenile ceroid-lipofuscinosis, residue 43 of the storage-body subunit
      c was previously found to be TML. In the present study, subunit c was isolated
      from the storage bodies of humans with juvenile ceroid-lipofuscinosis, and from
      sheep and mice with apparently analogous diseases. In all three species, partial
      amino acid sequence analysis of the stored subunit c indicated that the protein
      contained TML at residue 43. These findings strongly suggest that specific
      methylation of lysine residue 43 of mitochondrial ATP synthase plays a central
      role in the lysosomal storage of this protein.

PMID- 7575424
TI  - Homocysteine enhances the inhibitory effect of extracellular adenosine on the
      synthesis of proteins in isolated rat hepatocytes.
AB  - Previous work has shown that extracellular adenosine inhibits the incorporation
      of radiolabelled leucine into proteins in isolated rat hepatocytes [Tinton,
      Lefebvre, Cousin and Buc Calderon (1993) Biochim. Biophys. Acta 1176, 1-6]. In
      this study, we investigated whether its metabolism into adenine nucleotides,
      inosine or S-adenosylhomocysteine (AdoHcy) is required to induce such an
      impairment. Incubation of isolated hepatocytes in the presence of adenosine at
      0.5 or 1 mM reduces the synthesis of proteins by about 45% after 120 min of
      incubation. Such an inhibition occurred without cell lysis and was not modified
      by adding the adenosine kinase inhibitor 5-iodotubercidin (15 microM) or the
      adenosine deaminase inhibitor coformycin (0.1 microM). It is therefore unlikely
      that the anabolic and catabolic pathways of adenosine are involved in the
      inhibition of protein synthesis. Adenosine (1 mM) increased the level of AdoHcy
      and S-adenosylmethionine by 20- and 5-fold respectively after 60 min of
      incubation and reduced the methylation index. These events as well as the
      inhibition of protein synthesis were strongly enhanced in the presence of L
      homocysteine (2 mM). It is therefore concluded that the metabolism of adenosine
      into AdoHcy, which is known to be a potent inhibitor of cellular methylation
      reactions, may play an important role in the control of translation.

PMID- 7575425
TI  - Intracellular events in the assembly of very-low-density-lipoprotein lipids with
      apolipoprotein B in isolated rabbit hepatocytes.
AB  - Isolated rabbit hepatocytes incorporated [35S]methionine into cellular and
      secreted apolipoprotein B (apo-B), and [3H]glycerol into cellular and secreted
      triacylglycerol and phospholipids. Newly synthesized apo-B was incorporated into
      rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER), cis-Golgi
      and trans-Golgi membranes and was preferentially transferred into the lumen of
      the RER with specific radioactivities ten times those in the membrane.
      Radiolabelled apo-B did not equilibrate with pre-existing unlabelled apo-B, and
      pools of different specific radioactivities were established in different
      subcellular fractions. Only a small fraction of the newly synthesized apo-B was
      transferred to the Golgi lumen. In pulse-chase experiments, most of the newly
      synthesized apo-B in the RER membrane and the RER lumen was degraded.
      [3H]Glycerol was incorporated into triacylglycerol and phospholipids in the lumen
      of the RER, SER, cis-Golgi and trans-Golgi. However, in contrast with apo-B, all
      of the radiolabelled lipids in the lumen of the RER, SER and cis-Golgi were
      transferred to the trans-Golgi lumen or secreted. Analysis of the lipid
      composition of the lumenal content fractions suggests that, although very-low
      density-lipoprotein (VLDL) lipids are present in the endoplasmic reticulum lumen,
      a large fraction of these is not associated with apo-B. Collectively these
      observations suggest that assembly of apo-B into complete VLDL is not
      cotranslational, that most lipids become associated with apo-B late in the
      endoplasmic reticulum compartment and that the lipids are further modified in the
      Golgi lumen.

PMID- 7575427
TI  - Molecular cloning and deduced amino acid sequences of the alpha- and beta-
      subunits of mammalian NAD(+)-isocitrate dehydrogenase.
AB  - A 153 bp fragment of the cDNA encoding the beta-subunit of pig heart NAD(+)
      isocitrate dehydrogenase (NAD(+)-ICDH) was specifically amplified by PCR, using
      redundant oligonucleotide primers based on partial peptide sequence data [Huang
      and Colman (1990) Biochemistry 29, 8266-8273]. This PCR fragment was then used as
      a probe to isolate cDNA clones encoding the complete mature form of the beta
      subunit from a monkey testis cDNA library. Examination of the deduced amino acid
      sequence of the monkey subunit and the partial sequence of the pig heart enzyme
      revealed a high level of sequence conservation. In addition, 3 overlapping
      fragments of the cDNA for the alpha-subunit of monkey NAD(+)-ICDH were amplified
      using oligonucleotide primers derived from the cDNA sequence of a subunit of
      bovine NAD(+)-ICDH (EMBL accession no: U07980). These cDNA fragments allow
      deduction of the amino acid sequence of the alpha-subunit. Since the gamma
      subunit of monkey NAD(+)-ICDH has already been cloned [Nichols, Hall, Perry and
      Denton (1993) Biochem. J. 295, 347-350], a deduced amino acid sequence is now
      available for all three subunits of mammalian NAD(+)-ICDH. Interrelationships
      between these subunits are discussed and they are compared with the two subunits
      of yeast NAD(+)-ICDH and Escherichia coli NADP(+)-ICDH.

PMID- 7575426
TI  - Dolichol is not a necessary moiety for lipid-linked oligosaccharide substrates of
      the mannosyltransferases involved in in vitro N-linked-oligosaccharide assembly.
AB  - Dolichol is utilized in vivo as an unusually large anchor on which the precursor
      for N-linked oligosaccharides is assembled by a series of glycosyltransferases.
      The role of dolichol in enzyme substrate recognition is investigated. Thus the
      biosynthetic intermediate NN'-diacetylchitobiose was chemically linked to either
      dolichol or the much shorter fully saturated tetraisoprenoid phytanol. Both
      lipids were used as substrates by a recombinant, soluble beta-1,4
      mannosyltransferase. beta-[3H]Mannosylated lipids from this reaction were then
      used as substrates for the subsequent mannosyltransferases from yeast or rat
      liver microsomes. It was found that both the dolichyl- and phytanyl-linked
      substrates were easily mannosylated to form Man5GlcNAc2, with some further
      mannosylation to Man7GlcNAc2 and Man9GlcNAc2 at low concentrations of lipid
      linked substrate. It is concluded that dolichol is not necessary in vitro as part
      of the substrate for the mannosyltransferases in the biosynthetic pathway for N
      glycosylation.

PMID- 7575428
TI  - Regulation of expression of transcobalamin II receptor in the rat.
AB  - Surface and intracellular membrane distribution and hormonal regulation of
      transcobalamin II receptor (TC II-R) activity and protein levels have been
      studied in an effort to understand its regulation of expression in the rat. TC II
      R activity and the levels of the 62 kDa monomeric and 124 kDa dimeric forms of TC
      II-R were highest in the rat kidney and intestine, and in these tissues the
      receptor expression was not dependent upon the postnatal development of the rat.
      TC II-R expression was uniform in the various regions of the gut. Surface
      membrane distribution of TC II-R in the kidney revealed the expression of the 124
      kDa dimer form of TC II-R in the apical and basolateral membranes in the ratio of
      1:10. Further subcellular distribution of TC II-R in the kidney revealed the
      expression of the 124 kDa dimer in the intermicrovillar clefts and clathrin
      coated vesicles and the 62 kDa monomer in the microsomes. Neither the monomer nor
      the dimer could be detected in the early endosomes or lysosomes. Membrane TC II-R
      activity and TC II-R protein levels and cobalamin (Cbl; vitamin B12) transport in
      vivo were inhibited by about 90% in adrenalectomized rats and all three returned
      to normal levels by oral treatment of these animals with cortisone acetate. In
      contrast, thyroidectomy or experimentally induced diabetes had no effect on TC II
      R activity or Cbl transport. Based on these observations, we suggest that TC II-R
      expression is not developmentally or regionally regulated in rat renal and
      intestinal membranes and its expression in the kidney is asymmetrically
      distributed between the apical (10%) and basolateral (90%) membranes. In
      addition, our results also show that the dimerization of TC II-R is a post
      microsomal event and that the expression of TC II-R and plasma Cbl transport is
      regulated by cortisone.

PMID- 7575430
TI  - Effect of replacement of ferriprotoporphyrin IX in the haem domain of cytochrome
      P-450 BM-3 on substrate binding and catalytic activity.
AB  - Bacillus megaterium cytochrome P-450 BM-3 (coded by gene CYP102) is a
      catalytically self-sufficient mono-oxygenase, with both cytochrome P-450 and
      NADPH:cytochrome P-450 reductase domains, that catalyses the hydroxylation of
      fatty acids. The natural ferriprotoporphyrin IX has been removed from the haem
      domain of cytochrome P-450 BM-3 by treatment with acidified acetone, and it has
      been shown that, under carefully controlled conditions, haem can be added back to
      the resultant apoprotein to obtain a fully reconstituted haem domain with
      spectroscopic, substrate-binding and catalytic properties indistinguishable from
      those of the native domain. Replacement of the natural haem with
      ferriprotoporphyrin IX dimethyl ester yields a protein which has a higher
      affinity for the substrate dodecanoic acid and (in the presence of the reductase
      domain) the same catalytic rate as the native haem domain. Replacement with
      ferrimesoporphyrin IX yields a protein with the same affinity for substrate, but
      a reduced catalytic turnover. These results suggest that the haem moiety has a
      role in the creation of the binding pocket for substrate, and that modification
      of the electron density on the haem iron effects the catalytic rate.

PMID- 7575432
TI  - Mutations of the basic amino acid transporter gene associated with cystinuria.
AB  - To investigate the function of a basic and neutral amino acid transporter-like
      protein (rBAT) which is a candidate gene for cystinuria, we analysed the rBAT
      gene in cystinuric patients. Patient 1 is a compound heterozygote with mutations
      in the rBAT gene causing a glutamine-to-lysine transition at amino acid 268, and
      a threonine-to-alanine transition at amino acid 341, who inherited these alleles
      from his mother (E268K) and father (T341A), respectively. Injection of T341A and
      E268K mutant cRNAs into oocytes decreased transport activity to 53.9% and 62.5%
      of control (L-cystine transport activity in oocytes injected with wild-type rBAT
      cRNA), respectively. Co-injection of E268K and T341A into oocytes strongly
      decreased amino acid transport activity to 28% of control. On the other hand, co
      injection of wild-type and mutant rBAT did not decrease transport activity.
      Furthermore, immunological studies have demonstrated that the reduction of amino
      acid transport is not due to a decrease in the amount of rBAT protein expressed
      in oocyte membranes. These results indicate that mutations in the rBAT gene are
      crucial disease-causing lesions in cystinuria. In addition, co-injection
      experiments suggest that rBAT may function as a transport activator or regulatory
      subunit by homo- or hetero-multimer complex formation.

PMID- 7575431
TI  - Kinetic and spectroscopic studies on a superoxide dismutase from
      Propionibacterium shermanii that is active with iron or manganese: pH-dependence.
AB  - Kinetic studies were performed on the superoxide dismutases isolated from the
      anaerobic bacterium Propionibacterium shermanii as active enzymes with either
      iron or manganese, which were naturally incorporated into the same molecule
      depending on the metal supply. Both the Fe- and Mn- forms showed decreasing
      activity with increasing pH. This suggests the protonation of some groups near
      the metal, possibly a metal-bound water molecule. Thus the kinetic behaviour of
      this superoxide dismutase is much more dependent on the protein structure than on
      the metal incorporated into the active site. The secondary structures of both
      forms were not influenced by variations in pH, whereas the EPR spectra of the Fe
      superoxide dismutase changed as a function of pH. The EPR spectra apparently
      consist of two overlapping species. Steady-state experiments proved that all iron
      containing species show catalytic activity, but the species predominating in the
      alkaline pH range displays a lower reaction rate. The Michaelis constant and
      maximal turnover number for the Fe-superoxide dismutase were determined
      polarographically as Km = 0.54 mmol/l and Vmax. = 2000 mol.s-1 at pH 9.5. These
      data indicate that, in anaerobic bacteria under physiological conditions, the
      superoxide dismutase is not saturable with O2-. and the catalytic activity is
      similar to that of metal-specific Fe- or Mn-superoxide dismutases from aerobic
      organisms.

PMID- 7575429
TI  - The purification of a cysteine-dependent NAD+ glycohydrolase activity from bovine
      erythrocytes and evidence that it exhibits a novel ADP-ribosyltransferase
      activity.
AB  - An NAD+:cysteine ADP-ribosyltransferase activity was purified from bovine
      erythrocytes on the assumption that, like pertussis toxin, the enzyme would
      exhibit a cysteine-dependent NAD+ glycohydrolase activity. A three-step
      purification procedure was developed involving (1) precipitation with 40%
      (NH4)2SO4, (2) binding to a cysteine-Sepharose affinity column, and (3) binding
      to an NAD+ affinity column. PAGE showed a single band of M(r) 45,000. The enzyme
      had been purified 47,000-fold and had a specific activity of 1900 nmol
      nicotinamide released/min per mg. A study of the kinetic properties of this
      enzyme showed saturation kinetics for cysteine (Km = 4.0 mM). The ability of this
      enzyme to ADP-ribosylate protein was investigated using re-sealed inverted bovine
      erythrocyte ghosts. Incubation of the purified enzyme with erythrocyte ghosts and
      [adenylate-32P]NAD+ led to the enhanced dose-dependent labelling of several
      proteins, a doublet of high M(r) and proteins of M(r) 60,000, 55,000 and 29,000,
      identified by autoradiography of separated proteins on SDS/PAGE. The enzyme
      catalysed labelling of the major component at M(r) 55,000 was blocked by pre
      treatment of the erythrocyte ghosts with N-ethymaleimide, a sulphydryl alkylating
      agent, and the label was released by mercuric ion, but not by hydroxylamine.
      These experiments suggested that a cysteine residue on the target protein had
      been mono-ADP-ribosylated. This supposition was further supported by
      identification of the mercf1p4ion-released radiolabelled product as ADP-ribose by
      HPLC, and the observation that free ADP-ribose was unable to modify the membrane
      target protein directly.

PMID- 7575433
TI  - Differential expression of human Fas mRNA species upon peripheral blood
      mononuclear cell activation.
AB  - Human Fas/Apo-1 is a cell-surface protein that mediates apoptosis upon ligation
      with Fas ligand. The gene lies on the long arm of chromosome 10, consists of nine
      exons, and spans more than 26 kb of DNA. We previously reported the presence of a
      Fas variant mRNA, designated as Fas delta TM, in human peripheral blood
      mononuclear cells. Fas delta TM is generated by alternative splicing of the
      intact exon 6, which encodes the Fas transmembrane domain. In the present study,
      we describe three novel forms of Fas mRNA that are generated by alternative
      splicing of exons 3, 4, 6 and 7. These three mRNA variants undergo a frameshift
      and produce truncated polypeptides because of the appearance of a stop codon in
      the altered open reading frame. On activation of the peripheral blood mononuclear
      cells, a decreased expression of alternatively spliced Fas mRNA species
      correlated with increased cell-surface expression of Fas. These results suggest
      that differential expression of alternatively spliced Fas mRNAs may play a role
      in regulation of Fas function via regulation of the production of the membrane
      bound and the soluble, secreted Fas protein products.

PMID- 7575434
TI  - Identification, characterization and regional distribution in brain of RPDE-6
      (RNPDE4A5), a novel splice variant of the PDE4A cyclic AMP phosphodiesterase
      family.
AB  - COS-7 cells were transfected with a plasmid encoding a putative splice variant of
      PDE4A cyclic AMP-specific phosphodiesterase, RPDE-6 (RNPDE4A5). This led to the
      expression of a novel, cyclic AMP-specific, rolipram-inhibited phosphodiesterase
      activity. In such transfected cells a novel approximately 109 kDa species was
      recognized by anti-peptide sera raised against a dodecapeptide whose sequence is
      found at the extreme C-terminus of both RPDE-6 and another PDE4A splice variant.
      RD1 (RNPDE4A1A). RPDE-6 activity and immunoreactivity was found distributed
      between both pellet (approximately 25%) and cytosol (approximately 75%) fractions
      of transfected COS-7 cells. Soluble and pellet RPDE-6 activities exhibited
      similar low Km values for cyclic AMP (approximately 2.4 microM) and were both
      inhibited by low concentrations of rolipram, with IC50 values for the soluble
      activity being lower (approximately 0.16 microM) than for the pellet activity
      (approximately 1.2 microM). Pellet RPDE-6 was resistant to release by either high
      NaCl concentrations or the detergent Triton X-100. Probing brain homogenates with
      the anti-(C-terminal peptide) sera identified two immunoreactive species, namely
      an approximately 79 kDa species reflecting RD1 and an approximately 109 kDa
      species that co-migrated with the immunoreactive species seen in COS cells
      transfected to express RPDE-6. The approximately 109 kDa species was found
      distributed between both the low-speed (P1) and high-speed (P2) pellet fractions
      as well as the cytosol fractions derived from both brain and RPDE-6-transfected
      COS cells. In contrast, RD1 was found exclusively in the P2 fraction.
      Phosphodiesterase (PDE) activity immuno-precipitated by these antisera from brain
      cytosol had the characteristics of COS cell-expressed RPDE-6 with KmcyclicAMP
      approximately 3.7 microM and IC50rolipram approximately 0.12 microM. The
      distribution of PDE activity immunoprecipitated from the cytosol of various brain
      regions paralleled that seen for the distribution of the approximately 109 kDa
      immunoreactive species. It is suggested that the 109 kDa species identified in
      brain cytosol and pellet fractions is the native form of RPDE-6. The PDE4A splice
      variants, RD1 and RPDE-6, were shown to have distinct patterns of expression
      among various brain regions. PDE4A and PDE4B activities appear to provide the
      major source of PDE4 activity in brain membranes, whereas the cytosolic PDE4
      activity is suggested to reflect predominantly the activity of the PDE4D family.
      Alternative splicing of the PDE4A gene confers distinct N-terminal domains on
      RPDE-6 and RD1, which attenuates the Vmax. of these enzymes and defines their
      distinct subcellular distribution pattern.

PMID- 7575436
TI  - Arsenite release on enzymic transformation of arsonomethyl substrate analogues: a
      potentially lethal synthesis by glycerol-3-phosphate dehydrogenase.
AB  - The isosteric arsenical analogue of glycerol 3-phosphate, 3,4
      dihydroxybutylarsonic acid, is a good substrate for rabbit muscle glycerol-3
      phosphate dehydrogenase. Its oxidation is accompanied by release of arsenite.
      This release seems to be due to a spontaneous elimination of arsenite by 3
      oxoalkylarsonic acids, as it is also observed in (1) the oxidation of 3
      hydroxypropylarsonic acid by yeast alcohol dehydrogenase, (2) treatment of 3,4
      dihydroxybutylarsonic acid with periodate and (3) nonenzymic transamination of
      the glutamate analogue 2-amino-4-arsonobutyric acid. Enzymic formation of 3
      oxoalkylarsonic acids in cells can therefore be lethal, as arsenite is poisonous
      to most organisms because of its high affinity for dithiols such as dihydrolipoyl
      groups.

PMID- 7575435
TI  - Induction of Ca2+/calmodulin-stimulated cyclic AMP phosphodiesterase (PDE1)
      activity in Chinese hamster ovary cells (CHO) by phorbol 12-myristate 13-acetate
      and by the selective overexpression of protein kinase C isoforms.
AB  - The cAMP phosphodiesterase (PDE) activity of CHO cells was unaffected by the
      addition of Ca2+ +calmodulin (CaM), indicating the absence of any PDE1 (Ca2+/CaM
      stimulated PDE) activity. Treatment with the tumour promoting phorbol ester
      phorbol 12-myristate 13-acetate (PMA) led to the rapid transient induction of
      PDE1 activity which attained a maximum value after about 13 h before slowly
      decreasing. Such induction was attenuated by actinomycin D. PCR primers were
      designed to hybridize with two regions identified as being characteristic of PDE1
      forms found in various species and predicted to amplify a 601 bp fragment. RT-PCR
      using degenerate primers allowed an approx. 600 bp fragment to be amplified from
      RNA preparations of rat brain but not from CHO cells unless they had been treated
      with PMA. CHO cells transfected to overexpress protein kinase C (PKC)-alpha and
      PKC-epsilon, but not those transfected to overexpress PKC-beta I or PKC-gamma,
      exhibited a twofold higher PDE activity. They also expressed a PDE1 activity,
      with Ca2+/CaM effecting a 1.8-2.8-fold increase in total PDE activity. RT-PCR,
      with PDE1-specific primers, identified an approx. 600 bp product in CHO cells
      transfected to overexpress PKC-alpha and PKC-epsilon, but not in those
      overexpressing PKC-beta I or PKC-gamma. Treatment of PKC-alpha transfected cells
      with PMA caused a rapid, albeit transient, increase in PDE1 activity, which
      reached a maximum some 1 h after PMA challenge, before returning to resting
      levels some 2 h later. The residual isobutylmethylxanthine (IBMX)-insensitive PDE
      activity was dramatically reduced (approx. 4-fold) in the PKC-gamma
      transfectants, suggesting that the activity of the cyclic AMP-specific IBMX
      insensitive PDE7 activity was selectively reduced by overexpression of this
      particular PKC isoform. These data identify a novel point of 'cross-talk' between
      the lipid and cyclic AMP signalling systems where the action of specific PKC
      isoforms is shown to cause the induction of Ca2+/CaM-stimulated PDE (PDE1)
      activity. It is suggested that this protein kinase C-mediated process might
      involve regulation of PDE1 gene expression by the AP-1 (fos/jun) system.

PMID- 7575437
TI  - Solubilization and separation of two distinct carnitine acyltransferases from
      hepatic microsomes: characterization of the malonyl-CoA-sensitive enzyme.
AB  - Conditions have been developed for the solubilization of hepatic microsomal
      carnitine acyltransferase activity in good yield, with excellent long-term
      stability and with retention of malonyl-CoA sensitivity. Solubilized microsomal
      carnitine acyltransferase activity can be separated into malonyl-CoA-sensitive
      and -insensitive activities either by gel filtration on Superdex 200 or by anion
      exchange chromatography on Resource Q. On gel filtration the apparent molecular
      masses of the malonyl-CoA-sensitive and -insensitive activities are approx. 300
      kDa and 60 kDa respectively. The malonyl-CoA-sensitive and -insensitive
      activities have different fatty-acyl-chain-length specificities and different
      stabilities in the detergent octyl glucoside. Together these findings indicate
      that the malonyl-CoA-sensitive and -insensitive activities are due to different
      enzymes. The malonyl-CoA sensitivity of the inhibitable enzyme is markedly
      increased on reconstitution into soybean L-alpha-lecithin liposomes,
      demonstrating that phospholipids play a crucial role in the inhibition by this
      metabolite. Evidence is also provided that the malonyl-CoA-sensitive microsomal
      carnitine acyltransferase is a different enzyme from the malonyl-CoA-sensitive
      carnitine palmitoyltransferase found in the mitochondrial outer membrane. The
      possible physiological role of the two microsomal acyltransferases is discussed.

PMID- 7575438
TI  - The homeodomain protein IPF-1/STF-1 is expressed in a subset of islet cells and
      promotes rat insulin 1 gene expression dependent on an intact E1 helix-loop-helix
      factor binding site.
AB  - The mouse homeodomain protein insulin promoter factor-1 (IPF-1) and the rat
      homologue somatostatin transactivating factor-1 (STF-1) are involved in early
      pancreatic development and have been implicated in the cell-specific regulation
      of insulin- and somatostatin-gene expression in mature islet beta- and delta
      cells. The cell specificity of IPF-1/STF-1 expression in mature islets is,
      however, still unclear. Using antisera against recombinant IPF-1 and STF-1 in
      combination with antisera against islet hormones we find that all beta-cells in
      monolayers of newborn rat islet cells express STF-1, as do a fraction of the
      delta-cells. In adult rat and mouse pancreas we find a similar distribution. IPF
      1/STF-1 expression was not detected in glucagon-producing alpha-cells. In islet
      cell tumour models we found that a glucagon/islet amyloid polypeptide (IAPP)
      producing pluripotent rat islet cell line (NHI-6F-GLU) expresses STF-1 in all
      cells prior to insulin gene activation induced by in vivo culture. In contrast, a
      mouse alpha-cell line (alpha TC1) exclusively expressed IPF-1 in a small subset
      of insulin-producing cells while an insulin-negative subclone (alpha TC1.9) was
      negative for IPF-1. In transfection experiments using alpha TC1.9 cells STF-1
      activated a rat insulin 1 reporter gene dependent not only on both STF-1-binding
      sites, but also on the E1-binding site for the helix-loop-helix factor IEF-1.
      However, the endogenous mouse insulin genes remained inactive in these cells.
      These results suggest that the insulin promoter acquires its very high, yet cell
      specific, activity at least partly through the action of IPF-1/STF-1. This action
      is dependent on helix-loop-helix factors bound to the E1 element.

PMID- 7575440
TI  - Major changes in complex I activity in mitochondria from aged rats may not be
      detected by direct assay of NADH:coenzyme Q reductase.
AB  - We have investigated the respiratory activities and the concentrations of
      respiratory chain components of mitochondria isolated from the livers and hearts
      of two groups of rats aged 6 and 24 months respectively. In comparison with the
      adult controls (6 months), in aged rats there was a decline in total aerobic NADH
      oxidation in both tissues; only minor (non-significant) changes, however, were
      found in NADH:coenzyme Q reductase and cytochrome oxidase activities, and there
      was no change in ubiquinol-cytochrome c reductase activity. The coenzyme Q levels
      were slightly decreased in mitochondria from both organs of aged rats. The
      lowered NADH oxidase activity is not due to the slight decrease observed in the
      coenzyme Q levels, but is the result of decreased Complex I activity. Since the
      assay of NADH:coenzyme Q reductase requires quinone analogues, none of which can
      evoke its maximal turnover [Estornell, Fato, Pallotti and Lenaz (1993) FEBS Lett.
      332, 127-131], its activity has been calculated indirectly by taking advantage of
      the relationship that exists between NADH oxidation and ubiquinol oxidation
      through the coenzyme Q pool. The results, expressed in this way, show a drastic
      loss of activity of Complex I in both the heart and the liver of aged animals in
      comparison with adult controls.

PMID- 7575442
TI  - Expression of stress proteins and mitochondrial chaperonins in chronically
      stimulated skeletal muscle.
AB  - Molecular chaperones and cytosolic stress proteins are actively involved in the
      stabilization, import and refolding of precursor proteins into mitochondria. The
      purpose of the present study was to evaluate the relationship between
      mitochondrial content under steady-state conditions, and during the induction of
      organelle biogenesis, with the expression of stress proteins and mitochondrial
      chaperonins. A comparison of steady-state levels of mitochondrial enzyme activity
      [cytochrome c oxidase (CYTOX)] with chaperonin levels [the heat-shock protein
      HSP60, the glucose-regulated protein GRP75 (mtHSP70)] in striated muscles
      possessing a wide range of oxidative capacities revealed a proportional
      expression between the two. This relationship was disrupted by chronic
      contractile activity brought about by 10 days of 10 Hz stimulation of the
      tibialis anterior (TA) muscle, which induced 2.4-fold increases in CYTOX
      activity, but 3.2- and 9.3-fold increases in HSP60 and GRP75 respectively. The
      inducible stress protein HSP70i was detected at low levels in control TA muscle,
      and was increased 9.6-fold by chronic contractile activity, to values comparable
      with those found in the unstressed soleus muscle. This increase occurred in the
      absence of changes in type I MHC levels, indicating independent regulation of
      these genes. Despite the increases in HSP60 and HSP70i proteins, contractile
      activity did not alter their respective mRNA levels, illustrating post
      transcriptional mechanisms of gene regulation during contractile activity. In
      contrast, the mRNA levels encoding the co-chaperonin CPN10 were increased 3.3
      fold by contractile activity. Thus, the expression of individual mitochondrial
      chaperonins is independently regulated and uncoordinated. The extent of the
      induction of these stress proteins and chaperonins by contractile activity
      exceeded that of membrane enzymes (e.g. CYTOX). It remains to be determined
      whether this marked induction of proteins comprising part of the protein import
      machinery is beneficial for the translocation of enzyme precursors into the
      mitochondria during conditions of accelerated biogenesis.

PMID- 7575444
TI  - The refolding of hen egg white riboflavin-binding protein: effect of protein
      disulphide isomerase on the reoxidation of the reduced protein.
AB  - Hen egg white riboflavin-binding protein (RfBP) contains nine disulphide bonds.
      Provided these remain intact, the refolding of RfBP after incubation in 6 M
      guanidinium chloride is highly efficient with at least 95% of the binding
      activity regained within 3 min. Kinetic studies indicate that this regain
      consists of at least two phases. When the disulphide bonds of RfBP are reduced,
      reoxidation using a mixture of oxidized and reduced glutathione leads to less
      than 5% recovery of activity. However, if protein disulphide isomerase (PDI; EC
      5.3.4.1) is present during the reoxidation nearly 50% activity can be regained,
      suggesting that PDI may play an important role in the maturation of RfBP in vivo.

PMID- 7575445
TI  - Identification and subcellular localization of sphinganine-phosphatases in rat
      liver.
AB  - One of the primary products of [4,5-3H]sphinganine phosphate, added to fibroblast
      cultures, is sphinganine [Van Veldhoven and Mannaerts (1994) Biochem. J. 299, 597
      601], implicating the physiological action of (a) hitherto unknown
      phosphatase(s). We have now further characterized this activity in rat liver. In
      homogenates, the dephosphorylation appeared to be catalysed by multiple enzymes.
      A low-affinity system was active at acidic pH, whereas at physiological pH values
      hydrolysis was carried out by a high-affinity enzyme. The latter was sensitive to
      Zn2+ and detergents and possessed a pH optimum of 7.5. Upon cell fractionation
      the major portion of the high-affinity activity was recovered in the nuclear and
      microsomal fractions. Further separation of the microsomal fraction showed an
      association predominantly with vesicles derived from the plasma membrane.
      Likewise, when plasma membranes were prepared from the nuclear fraction, the high
      affinity phosphatase co-purified with the plasma membrane markers. From the
      differential effects of bivalent cations, chelators, water-soluble and
      amphiphilic phosphate esters, detergents and other compounds, it could be
      concluded that the plasma membrane-associated sphinganine-phosphatase activity is
      not due to alkaline phosphatase, dolichol-phosphatase, the N-ethylmaleimide
      insensitive phosphatidate phosphatase or ceramide-phosphatase. The
      dephosphorylation observed at acidic pH in homogenates appeared also to be
      enriched in purified plasma membranes and might represent a side-activity of
      ceramide-phosphatase. We speculate that the high-affinity phosphatase, which is
      especially active in neuronal tissues, plays a role in the attenuation of
      bioactive phosphorylated sphingoid bases such as sphingenine phosphate, and
      propose to name it sphingosine-phosphatase.

PMID- 7575443
TI  - Mass-spectrometric analysis of ADP-ribosylation factors from bovine brain:
      identification and evidence for homogeneous acylation with the C14:0 fatty acid
      (myristate).
AB  - The two proteins from bovine brain previously shown to be required for the
      guanosine 5'-[gamma-thio]triphosphate-dependent inhibition of a well
      characterized intra-Golgi transport assay, termed GGBF and GGBF, have been
      definitively identified as members of the ADP-ribosylation factor (ARF) family by
      electrospray MS analysis of the intact proteins, and of their tryptic fragments.
      Extensive protein-sequence information obtained from this analysis identified
      GGBF and GGBF as bovine ARF1 and ARF3 respectively. The sequence of bovine ARF3,
      which had not previously been determined, appears identical to that predicted
      from the rat and human ARF3 cDNAs. Further analysis of the N-terminal tryptic
      fragments of both bovine ARFs demonstrates N-terminal acylation solely with the
      C14:0 fatty acid (myristate). This finding establishes that the previously
      reported specific-activity difference between ARF1 and ARF3 in the intra-Golgi
      transport assay is not due to lipid heterogeneity at the N-terminus. This finding
      also indicates that the heterogeneity of N-terminal fatty-acyl groups previously
      observed on other myristoylated proteins is not universal.

PMID- 7575446
TI  - A novel phospholipase A2 from human placenta.
AB  - A major soluble phospholipase A2 of human term placenta was characterized and
      purified about 15,000-fold to homogeneity. The apparent molecular mass as
      determined in SDS/polyacrylamide gels is 42 kDa. The enzyme is inhibited by
      dithiothreitol indicating the presence of disulphide bridges which are essential
      for activity. Studies with known phospholipase A2 inhibitors revealed no
      immediate relationship to either secretory or cytosolic phospholipases A2. The
      placental enzyme prefers liposomes of phosphatidylcholine and has a distinct
      preference for arachidonic acid in the sn-2 position. It tolerates various
      detergents. Roughly 10 microM Ca2+ is required for activity, but it cannot be
      replaced by Mg2+ or Mn2+; Zn2+, Cu2+ and Fe3+ are inhibitory. In immunoblots, the
      placental enzyme was not detected by two separate antisera specific for type-II
      phospholipases A2 but reacted very weakly with antisera directed against
      cytosolic phospholipase A2. From these data we suggest that this enzyme is a
      novel form of phospholipase A2 which may be involved in arachidonic acid
      mobilization both during the course of pregnancy and at parturition.

PMID- 7575441
TI  - Heterologous processing of rat prosomatostatin to somatostatin-14 by PC2:
      requirement for secretory cell but not the secretion granule.
AB  - The role of PC2 in prosomatostatin (PSS) processing was investigated in GH3/GH4C1
      pituitary cells. These cells are sparsely granulated, express different amounts
      of PC2 and no PC1. We described heterologous processing of rat PSS (rPSS) co
      expressed with PC2 in stably transfected cells, correlate PC2 protein levels
      under different conditions of transfection with efficiency of PSS processing to
      somatostatin-14 (SS-14), determine the effect of modulating cell granularity on
      enzyme expression and PSS processing, and compare the relative potency of PC2
      with that of PC1, PSS and cleavage products were monitored by HPLC and
      radioimmunoassay of SS-like immunoreactivity (SSLI). Radioimmunoassay analysis of
      N-terminal PC2-like immunoreactivity (PC2 LI) in GH4C1:rPSS, GH4C1:rPSS + PC2 and
      GH3:rPSS transfectants showed a gradient of PC2 protein of 1:2.6:3.4 in cell
      extracts and 1:4.7:9 in secretion media from these cells respectively. The
      concentration of PC2 protein correlated with SS-14 conversion efficiency was 36
      +/- 3% in GH4C1:rPSS cells, 56 +/- 7% in GH4C1:rPSS-PC2 cells and 100% in
      GH3:rPSS cells. Treatment of GH4C1:rPSS + PC2 cells with epidermal growth factor,
      insulin, and beta-estradiol to induce granules, significantly increased basal and
      forskolin-stimulated co-release of SS LI and PC2 LI, but had no influence on SS
      14 processing efficiency. Hormone treatment led to a small increase in the ratio
      of mature PC2 (68 kDa) to proPC2 (75 kDa) forms. PC1 stably transfected in GH4C1
      cells produced significantly greater SS-14 conversion (62% in cells, 66% in
      media) compared with PC2 transfectants (53% in cells, 47% in media) These results
      provide the first proof that PC2 can effect dibasic processing of mammalian PSS,
      and, along with PC1, qualifies as an authentic SS-14 convertase. The activity of
      PC2 requires the milieu of the secretory cell but not the secretory granule.

PMID- 7575447
TI  - Regulation of the beta-lactamase BlaL of Streptomyces cacaoi: the product of the
      blaB regulatory gene is an internal membrane-bound protein.
AB  - The beta-lactamase-encoding gene blaL, cloned from Streptomyces cacaoi in
      Streptomyces lividans, is inducible by beta-lactam compounds. This regulation has
      been shown to depend on the products of two open reading frames, ORF1 (blaA) and
      ORF2 (blaB) [Lenzini, Magdalena, Fraipont, Joris, Matagne and Dusart (1992) Mol.
      Gen. Genet. 235, 41-48]. BlaA belongs to the LysR family of transcription
      activators, whereas BlaB shares some features with the penicillin-recognizing
      proteins. BlaB has now been overexpressed in Escherichia coli, purified and used
      for antibody preparation. Immunoblotting of cell-fractionated materials from S.
      cacaoi showed that BlaB is attached to the internal face of the cytoplasmic
      membrane. It could not be released by high salt concentrations or EDTA, but only
      by protease treatment. Under the assay conditions, BlaB did not act as a
      penicillin-binding protein, a beta-lactamase, a D-amino-peptidase or a target in
      a phosphorylation step.

PMID- 7575439
TI  - The toxicity in vitro of beta-amyloid protein.

PMID- 7575448
TI  - Failure of insulin-regulated recruitment of the glucose transporter GLUT4 in
      cardiac muscle of obese Zucker rats is associated with alterations of small
      molecular-mass GTP-binding proteins.
AB  - Cardiac ventricular tissue of lean and genetically obese (fa/fa) Zucker rats was
      used to study the expression, subcellular distribution and insulin-induced
      recruitment of the glucose transporter GLUT4 and to elucidate possible molecular
      alterations of the translocation process. Hearts were removed from basal and
      insulin-treated (20 min) lean and obese Zucker rats, and processed for
      subcellular fractionation and Western blotting of proteins. In obese rats, the
      total GLUT4 content in a crude membrane fraction was reduced to 75 +/- 8% (P =
      0.019) of lean controls. In contrast, GLUT4 abundance in plasma membranes was not
      significantly different between lean and obese rats with a concomitant decrease
      (47 +/- 3%) in the microsomal fraction of obese animals. In plasma membranes of
      lean animals insulin was found to increase the GLUT4 abundance to 294 +/- 43% of
      control with a significantly (P = 0.009) reduced effect in the obese group (139
      +/- 10% of control). In these animals insulin failed to recruit GLUT4 from the
      microsomal fraction, whereas the hormone induced a significant decrease (41 +/-
      4%) of microsomal GLUT4 in lean controls. In GLUT4-enriched membrane vesicles,
      obtained from cardiac microsomes of lean rats, a 24 kDa GTP-binding protein could
      be detected, whereas no significant labelling of this species was observed in
      GLUT4 vesicles prepared from obese animals. In addition to the translocation of
      GLUT4, insulin was found to promote the movement of the small GTP-binding protein
      rab4A from the cytosol (decrease to 61 +/- 13% of control) to the plasma membrane
      (increase to 177 +/- 19% of control) in lean rats with no effect of the hormone
      on rab4A redistribution in the obese group. In conclusion, cardiac glucose uptake
      of insulin-resistant obese Zucker rats is subject to multiple cellular
      abnormalities involving a reduced expression, altered redistribution and
      defective recruitment of GLUT4. We show here an association of the latter defect
      with alterations at the level of small GTP-binding proteins possibly leading to
      an impaired trafficking of GLUT4 in the insulin-resistant state.

PMID- 7575449
TI  - Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase
      and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations
      by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and
      triolein.
AB  - Different dietary fatty acids exert specific effects on plasma lipids but the
      mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol
      diets containing triacylglycerols enriched in specific saturated fatty acids, and
      effects on plasma lipids and the expression of genes involved in hepatic
      lipoprotein metabolism were measured. Trimyristin and tripalmitin caused
      significant rises in low-density lipoprotein (LDL) cholesterol which were
      accompanied by significant reductions in hepatic LDL receptor mRNA levels.
      Tripalmitin also increased hepatic expression of the apolipoprotein B gene,
      implying an increased production of LDL via very-low-density lipoprotein (VLDL)
      and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy
      3-methylglutaryl-CoA reductase mRNA did not vary significantly between the
      groups. Compared with triolein, tristearin had little effect on hepatic gene
      expression or total plasma cholesterol. However, it caused a marked decrease in
      VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to
      be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary
      stearate. The differential changes in plasma lipids and hepatic mRNA levels
      induced by specific dietary fats suggests a role for fatty acids or a metabolite
      thereof in the regulation of the expression of genes involved in lipoprotein
      metabolism.

PMID- 7575452
TI  - Triplex-DNA stabilization by hydralazine and the presence of anti-(triplex DNA)
      antibodies in patients treated with hydralazine.
AB  - Hydralazine is an antihypertensive drug that elicits andti-nuclear antibodies in
      patients as an adverse effect. We investigated the ability of hydralazine to
      promote/stabilize the triplex DNA form of poly(dA).2poly(dT). Under conditions of
      low ionic strength, the polynucleotide melted as a double helix with a melting
      temperature (Tm) of 55.3 degrees C. Hydralazine destabilized this duplex form by
      reducing its Tm to 52.5 degrees C. Spermidine (2.5 microM), a natural polyamine,
      provoked the triplex form of poly(dA)-.2poly(dT) with two melting transitions,
      Tm1 of 42.8 degrees C corresponding to triplex-->duplex+single-stranded DNA and
      Tm2 of 65.4 degrees C, corresponding to duplex melting. Triplex DNA thus formed
      in the presence of spermidine was further stabilized by hydralazine (250 microM)
      with a Tm1 of 53.6 degrees C. A similar stabilization effect of hydralazine was
      found on triplex DNA formed in the presence of 5 mM Mg2+. CD spectra revealed
      conformational perturbations of DNA in the presence of spermidine and
      hydralazine. These results support the hypothesis that hydralazine is capable of
      stabilizing unusual forms of DNA. In contrast with the weak immunogenicity of DNA
      in its right-handed B-DNA conformation, these unusual forms are immunogenic and
      have the potential to elicit anti-DNA antibodies. To test this possibility, we
      analysed sera from a panel of 25 hydralazine-treated patients for anti-(triplex
      DNA) antibodies using an ELISA. Our results showed that 72% of sera from
      hydralazine-treated patients contained antibodies reacting toward the triplex
      DNA. In contrast, there was no significant binding of normal human sera to
      triplex DNA. Taken together our data indicate that hydralazine and related drugs
      might exert their action by interacting with DNA and stabilizing higher-order
      structures such as the triplex DNA.

PMID- 7575451
TI  - Defective signal-transduction pathways in T-cells from autoimmune MRL-lpr/lpr
      mice are associated with increased polyamine concentrations.
AB  - We previously reported that difluoromethylornithine (DFMO), an inhibitor of
      polyamine biosynthesis, exerted significant beneficial effects on the lifespan
      and disease expression of MRL-lpr/lpr mice, which spontaneously develop a lupus
      like syndrome. Polyamine levels in splenic T-cells of MRL-lpr/lpr mice were
      significantly higher than those of Balb/c mice. In the present investigation, we
      examined the role of endogenous polyamines in transmembrane Ca2+ influx,
      generation of InsP3 and tyrosine phosphorylation of the p56lck protein in
      concanavalin A-stimulated splenic T-cells. Cytosolic free calcium concentrations
      ([Ca2+]i) in concanavalin A-stimulated T-cells of MRL-lpr/lpr and Balb/c mice
      were 250 +/- 25 and 450 +/- 42 nM respectively. Treatment of MRL-lpr/lpr mice
      with DFMO increased [Ca2+]i to 360 +/- 30 nM (P < 0.05). InsP3 levels of
      concanavalin A-stimulated MRL-lpr/lpr splenic T-cells were only 20% higher than
      those of unstimulated controls, whereas those of Balb/c T-cells were 90% higher.
      DFMO treatment increased InsP3 levels in concanavalin A-treated MRL-lpr/lpr T
      cells to 67%. Western-blot analysis showed a 7-fold higher level of p56lck
      phosphorylation of MRL-lpr/lpr splenic T-cells than that of Balb/c mice. DFMO
      treatment reduced tyrosine phosphorylation of p56lck of MRL-lpr/lpr mice
      significantly (P < 0.001). Two-colour flow-cytometric analysis revealed no
      significant difference in the CD4+/CD8+ ratio in splenic T-cells of MRL-lpr/lpr
      mice after DFMO treatment. Polyamine levels in splenocytes were significantly
      reduced by DFMO treatment. These data show that DFMO treatment could alter signal
      transduction pathways of splenic T-cells of MRL-lpr/lpr mice. Increased levels of
      polyamines in T-cells of untreated lpr mice contribute to defective signal
      transduction pathways and the pathogenesis of lupus-like symptoms.

PMID- 7575454
TI  - Magnetic circular dichroism study of the selenium-substituted form (Fe3Se4) of
      bovine heart aconitase.
AB  - The selenium-substituted inactive form of mitochondrial aconitase contains one
      [3Fe-4Se]1+/0 cluster [Surerus, Kennedy, Beinert and Munck (1989) Proc. Natl.
      Acad. Sci. U.S.A. 87, 9846-9850]. This cluster was studied in both oxidized and
      reduced states by magnetic CD (MCD) and EPR spectroscopy. In the MCD spectra,
      intensity and transition wavelength shifts are observed when compared with the
      spectra of the native [3Fe-4S]1+/0 cluster. These changes are used to
      differentiate between the charge-transfer transitions originating from inorganic
      and cysteinyl sulphur. Using also the data from the EPR spectra, the spin ground
      state is assigned as S = 1/2 for the oxidized [3Fe-4Se]1+ cluster and S = 2 for
      the reduced [3Fe-4Se]0 cluster.

PMID- 7575453
TI  - Role of cytosolic phospholipase A2 in arachidonic acid release of rat-liver
      macrophages: regulation by Ca2+ and phosphorylation.
AB  - In this study we have verified the existence of a cytosolic phospholipase A2
      (cPLA2) in rat-liver macrophages. Stimulation of these cells with phorbol 12
      myristate 13-acetate (PMA), zymosan and lipopolysaccharide (LPS), but not with
      the Ca(2+)-ionophore A23187, leads to phosphorylation of cPLA2 and activation of
      mitogen-activated protein (MAP) kinase, supporting the hypothesis that MAP kinase
      is involved in cPLA2 phosphorylation. We show furthermore, that the tyrosine
      kinase inhibitor genistein prevents the LPS- but not the PMA- or zymosan-induced
      phosphorylation of cPLA2 and activation of MAP kinase, indicating that tyrosine
      kinases participate in LPS- but not in PMA- and zymosan-induced cPLA2
      phosphorylation and MAP kinase activation. Phosphorylation of cPLA2 does not
      strongly correlate with stimulation of the arachidonic acid (AA) cascade: (1)
      A23187, a potent stimulator of AA release, fails to induce cPLA2 phosphorylation;
      (2) withdrawal of extracellular Ca2+, which inhibits PMA-stimulated AA release
      (Dieter, Schulze-Specking and Decker (1988) Eur. J. Biochem. 177, 61-67), has no
      effect on PMA-induced phosphorylation of cPLA2; (3) LPS induces cPLA2
      phosphorylation within minutes, whereas increased AA release upon treatment with
      LPS is detectable for the first time after 4 h; and (4) genistein, which prevents
      LPS-induced cPLA2 phosphorylation, does not inhibit AA release in response to
      LPS. From these data we suggest that a rise in intracellular Ca2+, but not
      phosphorylation of cPLA2, is essential for activation of the AA cascade in rat
      liver macrophages.

PMID- 7575450
TI  - Serine/threonine protein phosphatases.

PMID- 7575455
TI  - Reduced expression of kan-1 (encoding putative bile acid-CoA-amino acid N
      acyltransferase) mRNA in livers of rats after partial hepatectomy and during
      sepsis.
AB  - We isolated a cDNA clone, kan-1, from a rat liver cDNA library using a reverse
      transcriptase PCR cloning method. The kan-1 cDNA encoded a polypeptide of 420
      amino acids, and was 70 and 69% identical in nucleotide and amino acid sequences
      respectively with human liver bile acid-CoA-amino acid N-acyltransferase (BAT).
      Thus Kan-1 is probably a rat homologue of human BAT (rBAT). Kan-1/rBAT mRNA was
      mainly expressed in the livers of adult rats and rats immediately after, but not
      before, birth. It was expressed in the hepatocytes, the sinusoidal endothelial
      cells and the Kupffer cells of the liver. An anti-Kan-1/rBAT polyclonal antibody
      detected a protein of molecular mass 46 kDa in the liver. After partial
      hepatectomy, the levels of Kan-1/rBAT mRNA decreased at 6 and 12 h in the
      regenerating liver. In a sepsis model, hepatic expression of Kan-1/rBAT mRNA
      decreased at 6 and 12 h after caecal ligation and puncture. The kinetics of Kan
      1/rBAT mRNA expression suggests that it may play a role in acute-phase reactions.

PMID- 7575457
TI  - An unusual arrangement of 13 zinc fingers in the vertebrate gene Z13.
AB  - The zinc finger is a protein domain that imparts specific nucleic acid-binding
      activity on a wide range of functionally important proteins. In this paper we
      report the molecular cloning and characterization of a novel murine zinc-finger
      gene, mZ13. Analysis of mZ13 cDNAs revealed that the gene expresses a 794-amino
      acid protein encoded by a 2.7 kb transcript. The protein has an unusual
      arrangement of 13 zinc fingers into a 'hand' of 12 tandem fingers and a single
      isolated finger near the C-terminus. This structural organization is conserved
      with the probable chicken homologue, cZ13. mZ13 also contained an additional
      domain at the N-terminus which has previously been implicated in the regulation
      of zinc-finger transcription factor DNA-binding, via protein-protein
      interactions. mZ13 expression was detected in a wide range of murine embryonic
      and adult tissues. The structural organization of mZ13 and its expression profile
      suggest that it may function as a housekeeping DNA-binding protein that regulates
      the expression of specific genes.

PMID- 7575456
TI  - Characterization of bovine tracheobronchial phenol sulphotransferase cDNA and
      detection of mRNA regulation by cortisol.
AB  - Phenol sulphotransferases esterify both endogenous and foreign hydroxylated
      aromatic compounds with sulphate. Since these enzymes participate in both hormone
      and drug metabolism, elucidating their regulation at both the enzymic and
      molecular levels may provide new understanding in several metabolic pathways. The
      primary structure of a bovine phenol sulphotransferase has been determined by
      isolation of the corresponding cDNA. Two partial bovine cDNAs were first isolated
      by probing a tracheal epithelial cell lambda gt11 cDNA library with a rat phenol
      sulphotransferase cDNA. These clones provided the sequences of the 5' and 3' ends
      of the predicted coding region. A contiguous cDNA was subsequently isolated by
      PCR using 5' and 3' oligonucleotide primers and the cDNA library as the template.
      The sequence of the resulting approx. 1 kbp cDNA predicted an amino acid sequence
      that included sequences determined for several tryptic peptides of the purified
      protein. Antiserum directed to a synthetic N-terminal peptide predicted by the
      cDNA sequence showed reactivity with the purified enzyme. High-level Trc-promoter
      driven expression of the recombinant bovine enzyme was achieved in Escherichia
      coli. The bovine cDNA was used to determine relative steady-state levels of
      phenol sulphotransferase transcripts in bovine lung tissues; distal lung
      parenchymal RNA levels were 6-10-fold greater than those in tracheobronchial
      epithelium. Using a bronchial epithelial cell culture model, however, cortisol
      was observed to increase mRNA levels by 5-fold in both a dose- and time-dependent
      manner; this corresponds to previously reported glucocorticoid stimulation of
      phenol sulphotransferase activity in this system [Beckmann, Illig and Bartzatt
      (1994) J. Cell Physiol. 160, 603-610].

PMID- 7575459
TI  - Heparin proteoglycans synthesized by mouse mastocytoma contain chondroitin
      sulphate.
AB  - Proteoglycans (PGs), biosynthetically labelled with [35S]sulphate, were isolated
      from mouse mastocytoma tissue. Chromatography on antithrombin (AT)-Sepharose
      resulted in the separation of the 35S-labelled PGs into three fractions: PGs with
      no affinity for the gel (NA-PGs), PGs with low affinity (LA-PGs), and PGs with
      high affinity (HA-PGs) for antithrombin. Whereas NA-PGs contained almost
      exclusively chondroitin sulphate (CS), the AT-binding PGs contained 80-85%
      heparin and 15-20% CS. [35S]CS-containing macromolecules obtained from the HA-PG
      fraction after removal of the heparin polysaccharide chains were
      rechromatographed on AT-Sepharose. A majority of these 35S-labelled
      macromolecules no longer showed affinity for AT. These experiments indicate that
      the [35S]CS recovered in the AT-binding PGs is present in hybrid PGs.
      Polysaccharide chain-length determination demonstrated that the heparin chains
      were somewhat larger (M(r) approximately 30,000) than the CS chains in the NA-PGs
      (M(r) approximately 25,000). CS chains in the hybrid PGs were slightly smaller
      (M(r) approximately 20,000). Characterization of the sulphated CS disaccharides
      from NA- and HA-PGs showed that they contained similar amounts (20%) of
      disulphated disaccharides of [GlcA-GalNAc(4,6-di-OSO3)] type. The monosulphated
      CS-disaccharides were O-sulphated at C-4 of the galactosamine units. Analysis by
      gel chromatography of the [35S]CS components isolated from HA-PGs after
      heparinase treatment showed that a major portion of these contained one CS chain
      only. Calculations of the number of CS and heparin chains in AT-binding PGs,
      based on polysaccharide composition and polysaccharide chain length, indicate
      that all heparin-containing PGs are hybrids.

PMID- 7575458
TI  - Time-dependent effects of lithium on the agonist-stimulated accumulation of
      second messenger inositol 1,4,5-trisphosphate in SH-SY5Y human neuroblastoma
      cells.
AB  - In order to approach the molecular mechanism of Li+'s mood-stabilizing action,
      the effect of Li+ (LiCl) on inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] mass was
      investigated in human neuroblastoma SH-SY5Y cells, which express muscarinic M3
      receptors, coupled to PtdIns hydrolysis. Stimulation of these cells, with the
      cholinergic agonist acetylcholine, resulted in a rapid and transient increase in
      Ins(1,4,5)P3 with a maximum at 10 s. This was followed by a rapid decline in
      Ins(1,4,5)P3 within 30 s to a plateau level above baseline, which gradually
      declined to reach a new steady state, which was significantly higher than resting
      Ins(1,4,5)P3 at 30 min. Li+ had no effect on Ins(1,4,5)P3 in resting cells, as
      well as on the acetylcholine-dependent peak of Ins(1,4,5)P3. However, Li+ caused
      a transient reduction (at 45 s), followed by a long lasting increase in the
      Ins(1,4,5)P3 (30 min), as compared with controls. The Li+ effects were dose
      dependent and were observed at concentrations used in the treatment of bipolar
      disorders. Supplementation with inositol had no effect on the level of
      Ins(1,4,5)P3, at least over the time periods studied. Stimulation of muscarinic
      receptors with consequent activation of phospholipase C were necessary for the
      manifestation of Li+ effects in SH-SY5Y cells, Li+ did not interfere with
      degradation of Ins(1,4,5)P3 after receptor-blockade with atropine, suggesting
      that Li+ has no direct effect on the Ins(1,4,5)P3-metabolizing enzymes. A direct
      effect of Li+ on the phospholipase C also is unlikely. Blockade of Ca2+ entry
      into the cells by Ni2+, or incubation with EGTA, which reduces agonist-stimulated
      accumulation of Ins(1,4,5)P3, had no effect on the Li(+)-dependent increase in
      Ins(1,4,5)P3.

PMID- 7575461
TI  - Evidence for an essential serine residue in the active site of the Theta class
      glutathione transferases.
AB  - A consistent feature of the Alpha-, Mu- and Pi-class glutathione transferases
      (GSTs) is the presence near the N-terminus of a tyrosine residue that contributes
      to the activation of glutathione. While this residue appears to be conserved in
      many Theta-class GSTs, its absence in some suggested that the Theta-class GSTs
      may have a significantly different structure or catalytic mechanism. The
      elucidation of the crystal structure of the Theta-class GST from the Australian
      sheep blowfly, Lucilia cuprina, has indicated that a serine residue rather than a
      tyrosine residue can form a hydrogen bond with the glutathionyl sulphur atom. The
      present studies show that mutation of Ser-9 to alanine substantially inactivates
      the L. cuprina GST, confirming its importance in the reaction mechanism. As this
      serine is conserved in all Theta-class enzymes reported so far, it seems that an
      active-site serine is a significant factor that distinguishes the Theta-class
      GSTs from members of the Alpha-, Mu- and Pi-class isoenzymes.

PMID- 7575460
TI  - Structure and function of C-CAM1: effects of the cytoplasmic domain on cell
      aggregation.
AB  - C-CAMs are epithelial cell-adhesion molecules of the immunoglobulin supergene
      family with sequences highly homologous to carcinoembryonic antigen (CEA). C-CAMs
      and their human homologues, biliary glycoproteins, are unique among the CEA
      family proteins in that they have cytoplasmic domains. Furthermore, alternative
      splicing generates C-CAM isoforms with different cytoplasmic domains, suggesting
      that the cytoplasmic domains of C-CAM may play important roles in regulating the
      function or functions of C-CAM. By using both sense and antisense approaches, we
      have shown that C-CAM1 is a tumour suppressor in prostate carcinogenesis. This
      observation raises the possibility that the cytoplasmic domain of C-CAM1 may be
      involved in signal transduction or interaction with cytoskeletal elements to
      elicit the tumour suppressor function. The cytoplasmic domain of C-CAM1 contains
      several potential phosphorylation sites, including putative consensus sequences
      for cyclic AMP-dependent kinase and tyrosine kinase. One of the potential
      tyrosine phosphorylation sites is located within the antigen-receptor homology
      (ARH) domain. The ARH domain of the membrane-bound IgM molecule is necessary for
      signal transduction in B-cells. These structural features suggest that the
      cytoplasmic domain of C-CAM1 may be important for signal transduction. To test
      this possibility, we generated several site-directed C-CAM1 mutants and tested
      their ability to support adhesion and their abilities to be phosphorylated in
      vivo. Results from these studies revealed that Tyr-488 is phosphorylated in vivo.
      However, replacing this tyrosine with phenylalanine did not significantly
      compromise its adhesion function. Similarly, Ser and Thr residues are
      phosphorylated in vivo, but deletion of the potential cyclic AMP-dependent kinase
      site did not significantly reduce the adhesion function. These results suggest
      that the kinase phosphorylation sites in the cytoplasmic domain of C-CAM1 are not
      required for the adhesion function. However, these phosphorylation sites are
      probably involved in the regulation of C-CAM-mediated signal transduction. Thus,
      there are probably distinct structural requirements for the adhesion and the
      signal transduction functions of C-CAM. Incidentally, a C-CAM1 deletion mutant
      containing a 10-amino-acid cytoplasmic domain was able to support adhesion
      activity. This is in contrast to our previous finding that a C-CAM isoform, C
      CAM3, with a 6-amino-acid cytoplasmic domain could not support cell adhesion.
      This result indicates that the extra four amino acids, which are absent in C-CAM3
      and contain a potential Ser/Thr phosphorylation site, are important for the
      adhesion function.

PMID- 7575463
TI  - Muscarinic stimulation exerts both stimulatory and inhibitory effects on the
      concentration of cytoplasmic Ca2+ in the electrically excitable pancreatic B
      cell.
AB  - Mouse pancreatic islets were used to investigate how muscarinic stimulation
      influences the cytoplasmic Ca2+ concentration ([Ca2+]i) in insulin-secreting B
      cells. In the absence of extracellular Ca2+, acetylcholine (ACh) triggered a
      transient, concentration-dependent and thapsigargin-inhibited increase in
      [Ca2+]i. In the presence of extracellular Ca2+ and 15 mM glucose, ACh induced a
      biphasic rise in [Ca2+]i. The initial, transient phase increased with the
      concentration of ACh, whereas the second, sustained, phase was higher at low (0.1
      1 microM) than at high (> or = 10 microM) concentrations of ACh. Thapsigargin
      attenuated (did not suppress) the first phase of the [Ca2+]i rise and did not
      affect the sustained response. This sustained rise was inhibited by omission of
      extracellular Na+ (which prevents the depolarizing action of ACh) and by D600 or
      diazoxide (which prevent activation of voltage-dependent Ca2+ channels). During
      steady-state stimulation, the Ca2+ action potentials in B-cells were stimulated
      by 1 microM ACh but inhibited by 100 microM ACh. When B-cells were depolarized by
      45 mM K+, ACh induced a concentration-dependent, biphasic change in [Ca2+]i,
      consisting of a first peak rapidly followed by a decrease. Thapsigargin
      suppressed the peak without affecting the drop in [Ca2+]i. Measurements of 45Ca2+
      efflux under similar conditions indicated that ACh decreases Ca2+ influx and
      slightly increases the efflux. All effects of ACh were blocked by atropine. In
      conclusion, three mechanisms at least are involved in the biphasic change in
      [Ca2+]i that muscarinic stimulation exerts in excitable pancreatic B-cells. A
      mobilization of Ca2+ from the endoplasmic reticulum contributes significantly to
      the first peak, but little to the steady-state rise in [Ca2+]i. This second phase
      results from an influx of Ca2+ through voltage-dependent Ca2+ channels activated
      by a Na(+)-dependent depolarization. However, when high concentrations of ACh are
      used, Ca2+ influx is attenuated.

PMID- 7575462
TI  - Identification of a functional promoter element in the 5'-flanking region of the
      rat cMG1/TIS11b gene.
AB  - The cMG1 gene was originally identified as a mitogen-stimulated primary response
      gene. However, in contrast to genes such as c-fos and TIS11, cMG1 is also
      expressed at significant levels before and after the transient elevation induced
      by agonists. We have sequenced a 1.3 kb rat genomic cMG1 clone, which includes
      931 bp upstream of the transcription start site identified by primer-extension
      analysis. A 1033 bp fragment, including this 5'-flanking sequence, directed the
      expression of the reporter gene chloramphenicol acetyltransferase (CAT) in
      transfected NIH-3T3 cells. Progressive 5'-to-3' deletion indicated that an
      element located between -138 and -114 was responsible for most of this basal CAT
      expression. DNA mobility-shift assays showed that the sequence between -143 and 
      105 contained binding sites for cellular proteins, the principal complexes
      involving nucleotides between -119 and -105. We conclude that these complexes may
      represent the transcription factor-DNA element interactions that determine basal
      cMG1 expression.

PMID- 7575464
TI  - Extracellular ATP activates different signalling pathways in rat Sertoli cells.
AB  - 1. The present study describes effects of extracellular ATP (ATPe) on plasma
      membrane potential and cytoplasmic Ca2+ concentrations ([Ca2+]i) in rat Sertoli
      cells. Sertoli cells in suspension were stimulated with ATPe and other
      nucleotides and ionic changes were monitored utilizing the fluorescent dyes bis
      oxonol and fura-2/AM. ATPe induced a prompt plasma membrane depolarization which
      was dependent on Na+ influx from the extracellular medium, since it was abolished
      by omission of extracellular Na+. Depolarization was independent of [Ca2+]i rise
      as it also occurred in the absence of extracellular Ca2+ and after intracellular
      Ca2+ stores were discharged with thapsigargin. ATPe also stimulated a rapid and
      biphasic increase in [Ca2+]i: a prompt spike was followed by a prolonged
      sustained plateau. The initial spike was dependent on Ca2+ release from
      intracellular stores since it was also present when cells were incubated in EGTA
      supplemented Ca(2+)-free medium and was abolished by pretreatment with ionomycin
      and thapsigargin, agents that discharge intracellular Ca2+ stores. The sustained
      phase was dependent on Ca2+ influx from the extracellular medium as it was
      abolished when cells were incubated in EGTA-supplemented Ca(2+)-free medium. Ca2+
      influx was due to activation of voltage-operated calcium channels (VOCCs) since
      it was abolished by the VOCC inhibitors verapamil and nifedipine or incubation in
      sucrose medium, an experimental condition which precludes plasma membrane
      depolarization by ATPe. 2. ATPe-induced rises in intracellular Ca2+ concentration
      and plasma membrane depolarization were reduced by pretreatment with pertussis
      toxin, suggesting that ATPe-activated transduction mechanisms are in part under
      the control of pertussis toxin-sensitive G-proteins. These data show that Sertoli
      cells possess P2-purinergic receptor subtypes coupled to influx of Na+ and
      release of Ca2+ from intracellular stores and provide evidence for an activation
      of different pathways by extracellular ATPe. Activation of these receptors
      induces Na+ influx that causes a rapid plasma membrane depolarization.
      Furthermore, ATPe also triggers Ca2+ release from intracellular stores and Ca2+
      influx from extracellular space via dihydropyridine-sensitive VOCCs.

PMID- 7575465
TI  - Characterization by spectroscopic, kinetic and equilibrium methods of the
      interaction between recombinant human cystatin A (stefin A) and cysteine
      proteinases.
AB  - The near-UV spectroscopic changes induced by the binding of recombinant human
      cystatin A to papain were appreciably different from those induced by cystatin C,
      reflecting mainly interactions involving the single tryptophan of cystatin C, Trp
      106. Cystatin A bound tightly and rapidly to papain and cathepsin L, with
      dissociation equilibrium constants of approximately 10(-11)-10(-13) M and
      association rate constants of 3 x 10(6)-5 x 10(6) M-1.s-1. These affinities are
      at least 50-100-fold higher than previously reported values. The kinetics of
      binding to papain were consistent with a simple reversible bimolecular reaction
      mechanism, indicating that cystatin A, like chicken cystatin and cystatin C,
      binds to papain with no appreciable conformational adaptation of either reacting
      protein. Cystatin A bound more weakly to actinidin and cathepsins B, C and H,
      with dissociation equilibrium constants of 10(-8)-10(-9) M. The weaker binding to
      cathepsin B was largely due to a considerably reduced association rate constant
      (approximately 4 x 10(4) M-1.s-1), consistent with the 'occluding loop' of
      cathepsin B markedly restricting the access of cystatin A to the active site. The
      lower affinities for actinidin and cathepsins C and H were due partly to lower
      association rate constants (2 x 10(5)-6 x 10(5) M-1.s-1) but primarily to higher
      dissociation rate constants. The mode of binding of cystatin A to inactivated
      papains indicated that there is appreciably less space around the active-site
      cysteine of papain in the complex with cystatin A than in the complexes with
      chicken cystatin and cystatin C. An N-terminally truncated form of cystatin A,
      lacking the first six residues, had considerably lower affinity for papain than
      the full-length inhibitor, consistent with an intact N-terminal region being of
      importance for proteinase binding.

PMID- 7575466
TI  - Demonstration by pulsed neutron scattering that the arrangement of the Fab and Fc
      fragments in the overall structures of bovine IgG1 and IgG2 in solution is
      similar.
AB  - The bovine IgG1 and IgG2 isotypes exhibit large differences in effector
      functions. To examine the structural basis for this, the 12-domain structures of
      IgG1 and IgG2 were investigated by pulsed neutron scattering using a recently
      developed camera LOQ. This method reports on the average relative disposition in
      solution of the Fab and Fc fragments in IgG. The radii of gyration (RG) were
      found to be similar at 5.64 and 5.71 nm for IgG1 and IgG2 respectively in 100%
      2H2O buffers. The two cross-sectional radii of gyration (RXS) were also similar
      at 2.38-2.41 and 0.98-1.02 nm. Similar values were obtained for porcine IgG. Both
      bovine IgG1 and IgG2 possess similar overall solution structures, despite
      sequence differences at the hinge region at the centre of their structures. An
      automated computer survey of possible IgG structures was developed, in which
      coordinates for the two Fab fragments were displaced in a two-dimensional plane
      relative to those of the Fc fragment in 0.25 nm steps. The scattering curves
      calculated from these structures were found to be sensitive to relative
      displacements of the three fragments, but not on their rotational orientation
      about their longest axes. Good agreement with the solution scattering data was
      obtained with a planar IgG model in which the C-terminus of the CH1 domain of Fab
      was 3.6 nm from the N-terminus of Fc in both IgG1 and IgG2, with a precision of
      0.7 nm. Energy refinement showed that this spatial separation is compatible with
      the hinge sequences of bovine IgG1 and IgG2. The results show that multidomain
      protein structures can be modelled using LOQ data, and that a long hinge sequence
      does not necessarily reflect a large distance between Fab and Fc. The steric
      accessibility of Fc sites for interactions with cell-surface Fc receptors and C1q
      of complement is shown to be generally similar for IgG1 and IgG2, and the
      difference in effector function between IgG1 and IgG2 is probably based on
      deletions in the IgG2 hinge sequence.

PMID- 7575467
TI  - Molecular cloning of mouse intestinal trefoil factor and its expression during
      goblet cell changes.
AB  - A cDNA encoding mouse intestinal trefoil factor (mITF) was successfully cloned
      and sequenced from the small intestine of C57BL/6 mouse by using the combination
      of reverse transcription-PCR and rapid amplification of cDNA ends methods. The
      gene was, similar to rat and human ITFs, mainly expressed in the small and large
      intestine. The mITF expression was up-regulated during the recovery phase after
      depletion of goblet cells in acetic acid-induced colitis. On the other hand, the
      expression in the jejunum was not altered, while goblet cell hyperplasia was
      induced by Nippostrongylus brasiliensis infection. These results suggest that the
      mITF expression did not simply correlate with the number of goblet cells. The
      mITF may play an important role in the maintenance and repair of mucosal function
      of the rectum. Additionally, the mITF in the jejunum may play a role in
      alteration of the physicochemical nature of goblet cell mucins, thereby affecting
      the establishment of intestinal helminths.

PMID- 7575469
TI  - The biosynthesis of GDP-D-arabinopyranose in Crithidia fasciculata:
      characterization of a D-arabino-1-kinase activity and its use in the synthesis of
      GDP-[5-3H]D-arabinopyranose.
AB  - GDP-D-arabinopyranose (GDP-D-Ara) is the precursor of the uncommon D
      arabinopyranose residues present in the glycoconjugates of a few trypanosomatid
      parasites. Biosynthetic labelling experiments with Crithidia fasciculata showed
      that GDP-D-Ara could be labelled with [3H]D-Ara, [2-3H]D-Glc and [6-3H]D-Glc, but
      not with [1-3H]D-Glc, suggesting that D-Ara can be either taken up directly by
      the parasite or derived from D-Glc through a pathway involving the loss of carbon
      C-1. In vivo pulse-chase experiments indicated that D-Ara was sequentially
      incorporated into D-Ara-1-PO4 and GDP-D-Ara prior to transfer to the acceptor
      glycoconjugate, lipoarabinogalactan. An MgATP-dependent D-arabino-1-kinase
      activity present in soluble extracts of C. fasciculata was purified away from
      phosphatase activities by size-exclusion chromatography. The D-arabino-1-kinase
      had an apparent molecular mass of 600 kDa, a neutral optimum pH, and displayed
      substrate inhibition at D-Ara concentrations above 100 microM. It had a KmATP of
      1.7 mM and a KmAra of 24 microM. Competition studies indicated that the
      orientation of every single hydroxyl residue was important for D-Ara recognition
      by the enzyme, but that methyl or hydroxymethyl groups could be tolerated as
      equatorial substituents on C-5 of D-Ara. The partially purified D-arabino-1
      kinase activity was used in the chemico-enzymic synthesis of GDP-[5-3H]D-Ara from
      [6-3H]D-GlcN.

PMID- 7575468
TI  - Lysosomal processing of amyloid precursor protein to A beta peptides: a distinct
      role for cathepsin S.
AB  - To investigate the potential contribution of the lysosomal compartment in the
      processing of amyloid precursor protein (APP) to amyloid beta-peptides (A beta
      s), we stably overexpressed a series of lysosomal proteases (the cysteine
      proteases, cathepsins B, L and S, and the aspartic protease, cathepsin D) in a
      human kidney epithelial cell line (293) transfected to express high levels of
      beta APP. Preliminary experiments indicated that 293 cells endogenously
      synthesize cathepsins B, L and D, but not cathepsin S. A beta secretion was
      assessed by immunoprecipitation and ELISA and found to be increased approximately
      2-fold following cathepsin S expression, but to be unchanged (cathepsins B, L) or
      decreased (cathepsin D) in the other double transfectants. E-64d, an inhibitor of
      lysosomal cysteine proteases, significantly reduced A beta secretion by the
      cathepsin S transfectants, but had no effect on cells expressing the other
      proteases. Radiosequencing of A beta secreted by cathepsin S-expressing cells
      revealed that a previously unreported variant beginning at Met -1 (relative to
      the most common A beta N-terminus, Asp -1) accounted for most of the increase in
      A beta secretion. Immunostaining of human brain sections revealed cathepsin S in
      cortical neurons and glia in samples of brain from patients with Alzheimer's
      disease. These results provide evidence in living cells for a pathway in which
      cathepsin S generates A beta from amyloidogenic fragments of beta APP in the
      endosomal/lysosomal compartment. This pathway appears to be inducible, distinct
      from a constitutive pathway used by 293 and other cells to generate A beta, and
      may be relevant to the pathogenesis of Alzheimer's disease.

PMID- 7575470
TI  - Phosphatidylinositol 3-kinase activity is required for early endosome fusion.
AB  - The homotypic fusion between early endosomes from baby-hamster kidney cells is
      blocked by addition of the fungal metabolite wortmannin with an IC50 of approx.
      15 nM. Over this concentration range, wortmannin has been regarded as a specific
      inhibitor of phosphatidylinositol (PI) 3-kinase. Further confirmation of the
      participation of a PI 3-kinase in the fusion reaction has been obtained by
      demonstrating a sensitivity to an additional, structurally unrelated, PI 3-kinase
      inhibitor, LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]. Assays
      constructed such that only the membranous component has been incubated with
      wortmannin show in vitro fusion to be sensitive to treatment with the drug.
      Assays in which only the cytosolic component has been treated with wortmannin
      also showed inhibition of in vitro fusion, but to a lesser extent. PI 3-kinase
      action almost certainly involves direct regulation of membrane fusion, as no
      vesicular intermediate has been identified, despite previous extensive
      morphological examination of in vitro endosome fusions.

PMID- 7575473
TI  - Expression, purification and characterization of recombinant human N
      acetylgalactosamine-6-sulphatase.
AB  - Full-length cDNA sequences encoding human N-acetylgalactosamine-6-sulphatase were
      stably expressed in Chinese hamster ovary cells under the transcriptional control
      of the human polypeptide chain elongation factor 1 alpha gene promoter. A clonal
      cell line overexpressing recombinant N-acetylgalactosamine-6-sulphatase to a
      level of approx. 3 mg/l of culture medium was isolated. The secreted precursor
      enzyme was purified to homogeneity by a two-column procedure with an overall
      yield of 53% of the activity. The physical and catalytic parameters of the
      recombinant enzyme were similar to those of the mature form isolated from liver.
      On SDS/PAGE and gel filtration, recombinant N-acetylgalactosamine-6-sulphatase
      had a native molecular mass of 58-60 kDa. Recombinant N-acetylgalactosamine-6
      sulphatase was endocytosed by mucopolysaccharidosis IVA fibroblasts via the
      mannose-6-phosphate receptor-mediated pathway and was efficiently localized to
      lysosomes.

PMID- 7575471
TI  - Inhibition of asialoglycoprotein endocytosis and degradation in rat hepatocytes
      by protein phosphatase inhibitors.
AB  - In isolated rat hepatocytes, a radiolabelled tyramine-cellobiose conjugate of
      asialo-orosomucoid, 125I-TC-AOM, was rapidly taken up by receptor-mediated
      endocytosis and proteolytically degraded in the lysosomes, where radioactive
      degradation products accumulated. Okadaic acid and other protein phosphatase
      inhibitors (microcystin-LR, calyculin A) strongly reduced the fraction of
      asialoglycoprotein (ASGP) receptors localized to the cell surface, and
      correspondingly inhibited the uptake of 125I-TC-AOM. In addition, the inhibitors
      suppressed 125I-TC-AOM degradation strongly (90% at 150 nM) and potently (half
      maximal effect at 20 nM okadaic acid), indicating an involvement of protein
      phosphorylation, and of a protein phosphatase of type 2A, in the regulation of
      intracellular endocytic flux. The effects of okadaic acid on 125I-TC-AOM
      accumulation, as well as on degradation, could be eliminated by the protein
      kinase inhibitor genistein. Okadaic acid prevented the transfer of 125I-TC-AOM to
      a non-recycling endocytic compartment, causing its retention in a recycling
      compartment from which about one-third of the endocytosed 125I-TC-AOM could be
      returned to the cell surface and detached from its receptor in the presence of
      EGTA. ASGP receptors recycled extensively both in the presence and absence of
      okadaic acid, as indicated by a sustained uptake of 125I-TC-AOM. Sucrose density
      gradient analysis and sedimentation studies indicated that okadaic acid caused
      accumulation of 125I-TC-AOM in light endosomes (1.11 g/ml), preventing its
      transfer to dense endosomes (1.14 g/ml) and lysosomes (1.18 g/ml). The lysosomes
      could be identified in density gradients by their contents of lysosomal marker
      enzymes and acid-soluble radioactivity, and by their sensitivity towards the
      lysosome-disrupting agent glycyl-L-phenylalanine-2-naphthylamide. By using
      endocytosed AOM-gold particles as an ultrastructural endocytic marker, it could
      be shown that the light endosomes accumulating ASGP in the presence of okadaic
      acid had the morphological appearance of small endocytic vesicles/tubules and
      multivesicular endosomes. Whereas in control cells 4% of the AOM-gold was in
      small vesicles/tubules, 55% in multivesicular endosomes and 41% in lysosomes, the
      corresponding figures for okadaic acid-treated cells were 17%, 73% and 11%. Our
      results thus indicate that protein phosphatase inhibitors have two effects on
      ASGP endocytosis: (1) an early inhibition of ligand uptake, due to a reduction in
      the fraction of ASGP receptors at the cell surface, and (2) an inhibition of ASGP
      transfer from a recycling compartment consisting of light, small endocytic
      vesicles and multivesicular endosomes, to a non-recycling compartment consisting
      of dense multivesicular endosomes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7575472
TI  - Selective loss of the uncoupling protein from light versus heavy mitochondria of
      brown adipocytes after a decrease in noradrenergic stimulation in vivo and in
      vitro.
AB  - The relative stability against a decrease in adrenergic stimulation of the
      uncoupling protein (UCP) incorporated into different mitochondrial fractions was
      investigated in brown-fat-cell cultures. Cultures were initiated with
      undifferentiated cells from young mice and were acutely stimulated with
      noradrenaline at confluence (day 7). Cells were harvested just after the finish
      of the 24 h stimulation treatment or 24 h later, and three mitochondrial
      fractions were isolated by differential centrifugation: the M1 fraction (1000 g),
      the M3 fraction (3000 g) and the M15 fraction (15,000 g). The results obtained in
      vitro indicate that removal of adrenergic stimulation determines a selective loss
      of UCP from the lightest mitochondrial fractions (M3 and M15). Similar results
      were obtained in a situation in vivo (24 h starvation in mice) which is known to
      lead to a decreased noradrenaline input to brown adipose tissue, with decreased
      UCP levels. Thus brown adipocytes possess different mitochondrial subpopulations,
      which exhibit characteristic changes in their UCP turnover in response to
      thermogenic signals.

PMID- 7575477
TI  - Families, superfamilies and subfamilies of glycosyl hydrolases.

PMID- 7575474
TI  - Identification of histatins as tannin-binding proteins in human saliva.
AB  - Tannins have a number of detrimental biological effects and these include
      interference with normal growth and metabolism if they are present in the feed of
      various animals. Proline-rich proteins (PRPs) in saliva have been shown to
      provide protection against tannin, but little is known about the mechanism of
      protection and interaction of other salivary proteins with tannin. To identify
      tannin-binding human salivary proteins, parotid and submandibular/sublingual
      saliva samples were adsorbed with tannin. PRPs, and in particular a group of low
      M(r) proteins, were readily precipitated by tannin. The low-M(r) proteins were
      purified from parotid saliva and demonstrated to be histatins, a family of well
      characterized histidine-rich salivary proteins. The ability of synthetic histatin
      5, as well as an acidic PRP (PRP-1) and gelatin to precipitate quebracho
      condensed tannin and tannic acid was determined. At pH 7.4 histatin 5 was the
      most effective precipitant of both condensed tannin and tannic acid and it also
      precipitated the largest amount of condensed tannin at pH 3.0, but the smallest
      amount of tannic acid at that pH. In contrast PRP-1 showed a greater ability to
      precipitate both condensed tannin and tannic acid at pH 3.0 than at pH 7.4. Under
      most circumstances histatin 5 was therefore more effective in precipitating
      tannins than proteins with high proline content which generally have been
      recognized as strong precipitants of tannin. Pre-incubation of tannic acid with
      alpha-amylase inhibited the enzyme, but addition of histatin 5 or the acidic PRP
      PIF-s protected amylase from inhibition by tannin. Similarly salivary proteins
      may protect other biological activities in the digestive tract from inhibition by
      dietary tannin.

PMID- 7575476
TI  - Physiological control of metabolic flux: the requirement for multisite
      modulation.
AB  - Biochemists have long assumed that the flux through a metabolic pathway can be
      controlled by the activity of a key regulatory enzyme near the beginning of the
      pathway. We present the accumulating evidence that every step in this assumption
      is flawed. Instead, effective physiological control of metabolism is shown to
      involve simultaneous multisite modulation through action on a number of enzymes.

PMID- 7575478
TI  - Putative capacitative calcium entry channels: expression of Drosophila trp and
      evidence for the existence of vertebrate homologues.
AB  - Capacitative calcium entry is a major pathway through which intracellular calcium
      stores are refilled after stimulation. It has been suggested that the protein
      encoded by the transient receptor potential (trp) gene expressed in Drosophila
      photoreceptors may be homologous with capacitative calcium entry channels.
      Expression of the trp gene product in Xenopus oocytes led to significant
      increases in calcium entry only when the intracellular calcium stores were
      depleted. Previous investigations have found trp to be uniquely expressed in
      Drosophila photoreceptors, but PCR cloning shows that homologous proteins exist
      in Calliphora, mouse brain and Xenopus oocytes. It is thus possible that
      capacitative calcium entry in Xenopus oocytes is mediated by a homologue of trp.

PMID- 7575475
TI  - The DAG family of glycosyl hydrolases combines two previously identified protein
      families.

PMID- 7575479
TI  - The secreted form of the Alzheimer's beta-amyloid precursor protein stimulates a
      membrane-associated guanylate cyclase.
AB  - We previously demonstrated that secreted forms of the Alzheimer's beta-amyloid
      precursor protein (sAPP) elevate cyclic GMP (cGMP) in primary neuronal cultures
      and that this effect is responsible for the modulation of neuronal calcium
      homoeostasis by sAPP. We have investigated further the mechanism by which sAPP
      elevates cGMP. Inhibition of the formation of nitric oxide or carbon monoxide did
      not affect the ability of sAPP to lower rapidly intraneuronal calcium levels or
      elevate cGMP, suggesting that sAPP does not activate a soluble (cytosolic)
      guanylate cyclase. A dose-dependent stimulation of cGMP formation by sAPP was
      observed in brain membrane preparations. The stimulation was also dependent on
      the presence of ATP. These data suggest that sAPP activates a membrane-associated
      guanylate cyclase, perhaps similar to those present in the receptors for the
      natriuretic peptides and sperm motility factors.

PMID- 7575480
TI  - A novel lipid-binding protein from the cestode Moniezia expansa.
AB  - A lipid-binding protein (LBP) has been purified from the cytosol of the cestode
      Moniezia expansa. The native LBP was found to be an oligomer of approx. 250 kDa,
      consisting of 11 kDa monomers. The LBP bound saturated and unsaturated fatty
      acids, but not their CoA derivatives, with KD values in the range 0.68-7.8
      microM. Cholesterol, dihydroergosterol, bilirubin and retinoids were also bound,
      but alpha-tocopherol, bile acids, alk-2-enals and alka-2,4-dienals were not.
      Evidence suggests that there are two binding sites per subunit, each with
      different specificities. The fluorescent fatty acid 11-[(5
      dimethylaminonaphthalene-1-sulphonyl)amino]undecanoic acid (DAUDA) and retinol
      both showed an additional high-affinity binding site with a density of
      approximately 0.1 per subunit, suggesting specific binding to the oligomer. The
      amino acid composition of Moniezia LBP was distinct from that of previously
      characterized fatty acid-binding proteins (FABPs). The protein was not N
      terminally blocked and yielded a unique amino acid sequence, unrelated to that of
      any known FABP; there was also evidence of microheterogeneity. Polyclonal
      antibodies raised to the Moniezia protein did not cross-react with mammalian,
      nematode or digenean FABP. The Gibbs free energy for protein folding (13.02
      kJ/mol; 3.1 kcal/mol), determined by urea denaturation, was identical for both
      the native and ligand-bound Moniezia LBP. CD spectra showed that the Moniezia
      protein contained 36% alpha-helix and that the secondary structure underwent only
      minor changes on ligand binding. Moniezia LBP binds a range of anthelmintics,
      with KD values again in the range 0.66-7.3 microM. It is possible that, in
      helminths, binding proteins may play a role in determining the specificity and
      site of action of anthelmintics.

PMID- 7575481
TI  - Insulin and insulin-like growth factor I (IGF-I) stimulate GLUT4 glucose
      transporter translocation in Xenopus oocytes.
AB  - 1. The heterologous expression of glucose transporters GLUT4 and GLUT1 in Xenopus
      oocytes has been shown to cause a differential targeting of these glucose-carrier
      isoforms to cellular membranes and a distinct induction of glucose transport
      activity. In this study we have evaluated the effect of insulin and insulin-like
      growth factor I (IGF-I) on glucose uptake and glucose transporter distribution in
      Xenopus oocytes expressing mammalian GLUT4 and GLUT1 glucose carriers. 2. Insulin
      and IGF-I stimulated 2-deoxyglucose uptake in GLUT4-expressing oocytes, but not
      in GLUT1-expressing oocytes or in water-injected oocytes. The stimulatory effect
      of insulin and IGF-I on 2-deoxyglucose uptake in GLUT4-expressing oocytes
      occurred via activation of the IGF-I receptor. 3. Subcellular-fractionation
      studies indicated that insulin and IGF-I stimulated translocation of GLUT4 to the
      cell surface of the oocyte. 4. Incubation of intact oocytes with insulin
      stimulated phosphatidylinositol 3-kinase activity, an effect that was blocked by
      the additional presence of wortmannin. Furthermore, wortmannin totally abolished
      the insulin-induced stimulation of 2-deoxyglucose uptake in GLUT4-expressing
      oocytes. 5. In this study, both the insulin-induced GLUT4 carrier translocation
      and GLUT4-dependent insulin-stimulated glucose transport have been reconstituted
      in the Xenopus oocyte. These observations, together with the fact that
      wortmannin, as found in adipocytes, inhibits insulin-stimulated glucose transport
      in oocytes, suggest that the heterologous expression of GLUT4 in oocytes is a
      useful experimental model by which to study the cell biology of insulin-induced
      GLUT4 translocation.

PMID- 7575482
TI  - Cellobiohydrolase B, a second exo-cellobiohydrolase from the cellulolytic
      bacterium Cellulomonas fimi.
AB  - The gene cbhB from the cellulolytic bacterium Cellulomonas fimi encodes a
      polypeptide of 1090 amino acids. Cellobiohydrolase B (CbhB) is 1037 amino acids
      long, with a calculated molecular mass of 109765 Da. The enzyme comprises five
      domains: an N-terminal catalytic domain of 643 amino acids, three fibronectin
      type III repeats of 97 amino acids each, and a C-terminal cellulose-binding
      domain of 104 amino acids. The catalytic domain belongs to family 48 of glycosyl
      hydrolases. CbhB has a very low activity on CM-cellulose. Viscometric analysis of
      CM-cellulose hydrolysis indicates that the enzyme is an exoglucanase. Cellobiose
      is the major product of hydrolysis of cellulose. In common with two other
      exoglycanases from C. fimi, CbhB has low but detectable endoglucanase activity.
      CbhB is the second exo-cellobiohydrolase found in C. fimi. Therefore, the
      cellulase system of C. fimi resembles those of fungi in comprising multiple
      endoglucanases and cellobiohydrolases.

PMID- 7575483
TI  - Quantification of signalling components and amplification in the beta-adrenergic
      receptor-adenylate cyclase pathway in isolated adult rat ventricular myocytes.
AB  - We have investigated the stoichiometric relationship of proteins involved in beta
      adrenergic-receptor-mediated signal transduction in isolated rat cardiac
      myocytes. These cells contain about 2.1 x 10(5) beta-adrenergic receptors per
      cell, as determined by radio-ligand-binding assays. We have assessed the amount
      of Gs alpha present in myocyte membranes by immunoblotting using a purified
      glutathione S-transferase-Gs alpha fusion protein as a standard for
      quantification. By this method, we determined that cardiac myocytes contain about
      35 x 10(6) and 12 x 10(6) molecules per cell of the 45 and 52 kDa forms of Gs
      alpha, respectively. [3H]Forskolin binding assays were used to assess the
      formation of high-affinity forskolin binding sites representing Gs alpha
      adenylate cyclase complexes occurring in response to Gs alpha activation.
      Quantification of the adenylate cyclase complexes was facilitated by the
      permeabilization of cells with saponin. The addition of isoprenaline
      (isoproterenol) and guanosine 5'-[gamma-thio]trisphosphate to saponin
      permeabilized myocytes results in the formation of 6 x 10(5) Gs alpha-adenylate
      cyclase complexes. Taken together, the data presented here demonstrate that, in a
      physiologically relevant setting, G-protein is present in large stoichiometric
      excess relative to both receptor and effector. In addition, we show that,
      overall, only modest signal amplification occurs between receptor and adenylate
      cyclase. Thus adenylate cyclase (rather than Gs) is the component distal to
      receptor that limits agonist-mediated increases in cyclic AMP production.
      Although limited data are as yet available for other G-protein-regulated
      effectors, we hypothesize that the stoichiometry of signalling components and the
      extent of signal amplification described for the beta-adrenergic response pathway
      will be applicable to other G-protein-coupled hormone receptor systems.

PMID- 7575484
TI  - Naphthalenesulphonamides block neutrophil superoxide production by intact cells
      and in a cell-free system: is myosin light chain kinase responsible for these
      effects?
AB  - Selective antagonists of myosin light chain kinase (MLCK) [e.g. ML-7; 1-(5
      iodonaphthalene-1-sulphonyl)-1H-hexahydro-1,4-diazepine hydrochloride] were found
      to inhibit superoxide (O2-) release from stimulated neutrophils. The
      concentrations of ML-7 that were inhibitory were substantially lower than those
      reported for a selective antagonist of protein kinase C [i.e. H-7; 1-(5
      isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride]. ML-7 also reduced the
      phosphorylation of the 47 kDa subunit of the NADPH-oxidase system (p47-phox) and
      blocked translocation of this protein to the Triton X-100-insoluble fraction in
      stimulated cells. Interestingly, ML-7 also inhibited O2- production in a cell
      free system derived from neutrophils at concentrations similar to those that were
      effective in vivo. This cell-free system does not require ATP and is insensitive
      to all other inhibitors of protein kinases tested, including some highly
      effective against MLCK (i.e. staurosporine). Thus, the data suggest that ML-7
      does not block O2- release by inhibiting a protein kinase but instead may
      interact directly with a subunit of the oxidase. The binding site for ML-7 may
      provide a valuable target for inhibiting the inflammatory properties of
      phagocytic leucocytes by naphthalenesulphonamides designed to lack activity
      against protein kinases.

PMID- 7575486
TI  - Increase in receptor-like protein tyrosine phosphatase activity and expression
      level on density-dependent growth arrest of endothelial cells.
AB  - Protein tyrosine phosphatase (PTPase) activity was examined in two cell lines:
      human umbilical vein endothelial (HUVE) cells, which display contact inhibition
      of cell growth, and A427 human adenocarcinoma cells, which have lost this
      ability. HUVE cells harvested at high density displayed a 10-fold increase in
      membrane-associated PTPase activity. A427 cells exhibited no such phenomenon.
      Moreover, modification of HUVE cell growth rate by a stimulating agent such as
      basic fibroblast growth factor or by blocking compounds such as thymidine or
      suramin resulted in no change in PTPase activity, suggesting that the observed
      increase in membrane-associated activity at confluency was specific for cell-cell
      contact-directed growth arrest. The expression of various PTPase mRNAs was
      examined in HUVE and A427 cells. Of the receptor-like PTPases tested, two were
      exclusively expressed in HUVE cells (PTP gamma and HPTP beta). Only HPTP beta,
      which is structurally similar in its extracellular region to cell-adhesion
      receptors of the immunoglobulin superfamily, displayed a pattern of expression
      related to the increase in PTPase activity. Competitive PCR was used to quantify
      its expression during cell culture. A 12-fold increase in HPTP beta mRNA
      expression was detected and it parallelled the time course of PTPase activity.
      This observation strongly implicates receptor-like PTPases in density-dependent
      growth arrest.

PMID- 7575485
TI  - The protein phosphatase inhibitor calyculin A stimulates chemokine production by
      human synovial cells.
AB  - Cultured human synovial fibroblasts express mRNA for the chemotactic cytokines
      (chemokines) interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and
      regulated upon activation normal T-cell expressed and presumably secreted
      (RANTES), when stimulated with IL-1 or tumour necrosis factor alpha (TNF alpha).
      Calyculin A, a potent type 1/2A protein serine/threonine phosphatase inhibitor,
      was used to examine the role of protein phosphatases in the regulation of
      chemokine gene expression. Calyculin A (1 nM) mimicked IL-1 by inducing IL-8 and
      MCP-1 mRNA expression in synovial cells. IL-8 mRNA was induced over a similar
      time period (1-6 h) in response to IL-1 or calyculin A, whereas MCP-1 mRNA was
      induced more rapidly (1-2 h) by calyculin A than by IL-1 (4-6 h). Expression of
      RANTES mRNA occurred in response to TNF alpha, but could not be induced by
      stimulation with calyculin A alone. These results suggest that inhibition of
      protein phosphatase type 1/2A may have a differential role in the regulation of
      the expression of each of the chemokine genes. Synovial fibroblasts also secreted
      IL-8 and IL-6 peptide when stimulated with either IL-1/TNF alpha or calyculin A.
      The amount of IL-8 and IL-6 peptide produced in response to calyculin A was
      significantly increased above that produced by untreated synovial cells, though
      it was much less than the amount induced by IL-1 or TNF alpha. Calyculin A also
      acted synergistically with IL-1 or TNF alpha to cause a 2-fold potentiation of IL
      1- or TNF alpha-induced IL-8 mRNA and peptide and RANTES mRNA expression. These
      results suggest that although inhibition of a protein phosphatase may be able to
      regulate the magnitude of IL-1-induced chemokine gene expression, the IL-1 signal
      transduction pathway involves components in addition to phosphatase inhibition,
      possibly including the activation of a protein kinase, the action of which may be
      opposed by a protein phosphatase inhibited by calyculin A.

PMID- 7575487
TI  - The cell cycle in growth and development: a special issue.

PMID- 7575488
TI  - Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle.
AB  - Passage through the cell cycle requires the successive activation of different
      cyclin-dependent protein kinases (CDKs). These enzymes are controlled by
      transient associations with cyclin regulatory subunits, binding of inhibitory
      polypeptides and reversible phosphorylation reactions. To promote progression
      towards DNA replication, CDK/cyclin complexes phosphorylate proteins required for
      the activation of genes involved in DNA synthesis, as well as components of the
      DNA replication machinery. Subsequently, a different set of CDK/cyclin complexes
      triggers the phosphorylation of numerous proteins to promote the profound
      structural reorganizations that accompany the entry of cells into mitosis. At
      present, much research is focused on elucidating the links between CDK/cyclin
      complexes and signal transduction pathways controlling cell growth,
      differentiation and death. In future, a better understanding of the cell cycle
      machinery and its deregulation during oncogenesis may provide novel opportunities
      for the diagnostic and therapeutic management of cancer and other proliferation
      related diseases.

PMID- 7575489
TI  - G1 regulation and checkpoints operating around START in fission yeast.
AB  - Three major aspects of G1 regulation acting at START in fission yeast are
      discussed in this review. Firstly, progression towards S phase in the mitotic
      cycle. This is controlled by the activation of transcription complexes at START
      which cause cell cycle-dependent activation of genes required for DNA synthesis.
      The second aspect is the regulation of developmental fate occurring during G1.
      Passage through START appears to inhibit sexual differentiation because the
      meiotic and mitotic pathways are mutually exclusive. This is brought about
      because the meiotic pathway is inhibited by the same gene functions that are
      required for S phase onset. Thirdly, distinct checkpoint, or dependency, controls
      operate both pre- and post-START in the mitotic cycle to inhibit mitosis in the
      absence of replicated DNA, and also to limit rounds of DNA replication to one per
      cell cycle.

PMID- 7575490
TI  - Calcium signalling and cell proliferation.
AB  - The orderly sequence of events that constitutes the cell cycle is carefully
      regulated. A part of this regulation depends upon the ubiquitous calcium
      signalling system. Many growth factors utilize the messenger inositol
      trisphosphate (InsP3) to set up prolonged calcium signals, often organized in an
      oscillatory pattern. These repetitive calcium spikes require both the entry of
      external calcium and its release from internal stores. One function of this
      calcium signal is to activate the immediate early genes responsible for inducing
      resting cells (G0) to re-enter the cell cycle. It may also promote the initiation
      of DNA synthesis at the G1/S transition. Finally, calcium contributes to the
      completion of the cell cycle by stimulating events at mitosis. The role of
      calcium in cell proliferation is highlighted by the increasing number of
      anticancer therapies and immunosuppressant drugs directed towards this calcium
      signalling pathway.

PMID- 7575491
TI  - Tumour suppressors, kinases and clamps: how p53 regulates the cell cycle in
      response to DNA damage.
AB  - The human tumour suppressor protein p53 is critical for regulation of the cell
      cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral
      infection, cells respond rapidly by arresting the cell cycle. A G1 arrest
      requires the activity of wild-type p53, as it is not observed in cells lacking
      functionally wild-type protein, and at least some component of S phase and G2/M
      arrests is also thought to be p53-dependent. p53 functions as a transcription
      factor which binds specific DNA sequences, and recently major downstream targets
      have been identified, including p21Cip1, an inhibitor of the cell cycle kinases
      that also blocks the replicative but not the repair function of DNA polymerase
      delta auxiliary factor, PCNA. Current interest focuses on developing novel cancer
      therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell
      cycle.

PMID- 7575493
TI  - Frontier questions about sister chromatid separation in anaphase.
AB  - Sister chromatid separation in anaphase is an important event in the cell's
      transmission of genetic information to a descendent. It has been investigated
      from different aspects: cell cycle regulation, spindle and chromosome dynamics
      within the three-dimensional cell architecture, transmission fidelity control and
      cellular signaling. Integrated studies directed toward unified understanding are
      possible using multidisciplinary methods with model organisms. Ubiquitin
      dependent proteolysis, protein dephosphorylation, an unknown function by the TPR
      repeat proteins, chromosome transport by microtubule-based motors and DNA
      topological change by DNA topoisomerase II are all necessary for progression from
      metaphase to anaphase. Chromosome condensation, mitotic kinetochore function and
      spindle formation require a larger number of proteins, which are prerequisites
      for successful sister chromatid separation. Factors that help to retain sister
      chromatid connection after replication and prevent premature separation remain to
      be determined. Although sister chromatid separation occurs in anaphase, gene
      functions in other cell cycle stages also ensure the progression of correct
      chromatid separation.

PMID- 7575492
TI  - Human papillomavirus E6 and E7: proteins which deregulate the cell cycle.
AB  - Numerous clinical, epidemiological and molecular findings link some types of
      Human Papillomaviruses (HPV) with cancer of the genital tract. They share a
      common pathway of transformation with a number of DNA tumour viruses, such as
      Adenovirus and SV40. Although all these viruses are termed 'DNA tumour viruses'
      and have similar in vitro transforming activities, Human Papillomavirus is the
      only one so far clearly involved in human cancer. Extensive studies on HPV E6 and
      E7 proteins have demonstrated their involvement in malignant transformation. E6
      and E7 bind the products of tumour suppressor genes, p53 and Rb1, respectively,
      modifying or inactivating their normal functions. The Rb1 and p53 genes are
      deleted or mutated in several cancers and both proteins regulate the
      transcription of genes involved in cell cycle progression control. The E6/p53 and
      E7/Rb1 interactions result in a deregulation of the cell cycle with loss of
      control of crucial cellular events, such as DNA replication, DNA repair and
      apoptosis.

PMID- 7575494
TI  - Overview of controls in the Escherichia coli cell cycle.
AB  - The harmonious growth and cell-to-cell uniformity of steady-state bacterial
      populations indicate the existence of a well-regulated cell cycle, responding to
      a set of internal signals. In Escherichia coli, the key events of this cycle are
      the initiation of DNA replication, nucleoid segregation and the initiation of
      cell division. The replication initiator is the DnaA protein. In nucleoid
      segregation, the MukB protein, required for proper partitioning, may be a member
      of the myosin-kinesin superfamily of mechanoenzymes. In cell division, the FtsZ
      protein has a tubulin motif, is a GTPase and polymerizes in a ring around midcell
      during septation; the FtsA protein has an actin-like structure. The nature of the
      internal signals triggering these events is not known but candidates include cell
      mass, the superhelical density of the chromosome and the concentration of two
      regulatory nucleotides, cyclic AMP and ppGpp. The involvement of cytoskeletal
      like proteins in key cycle events encourages the notion of a fundamental
      biological unity in cell cycle regulation in all organisms.

PMID- 7575495
TI  - Origins of G1 arrest in senescent human fibroblasts.
AB  - Human diploid fibroblasts have a finite proliferative lifespan in culture, at the
      end of which they are arrested with G1 phase DNA contents. Upon serum
      stimulation, senescent cells are deficient in carrying out a subset of early
      signal transduction events such as activation of protein kinase C and induction
      of c-fos. Later in G1, they uniformly fail to express late G1 genes whose
      products are required for DNA synthesis, implying that they are unable to pass
      the R point. Failure to pass the R point may occur because senescent cells are
      unable to phosphorylate the retinoblastoma protein, owing to the accumulation of
      inactive complexes of cyclin E/Cdk2 and possibly cyclin D/Cdk4. Senescent cells
      contain high amounts of p21, a potent cyclin-dependent kinase inhibitor whose
      levels are also elevated in cells arrested in G1 following DNA damage, suggesting
      that both arrests might share a common mechanism. Cell aging is accompanied by a
      progressive shortening of chromosomal telomeres, which could be perceived by the
      cells as a form of DNA damage that gives rise to the signals that inactive the
      cell cycle machinery.

PMID- 7575496
TI  - Stopped for repairs.
AB  - The tumor suppressor protein p53 is intimately involved in the cellular response
      to DNA damage, controlling cell cycle arrest, apoptosis and the transcriptional
      induction of DNA damage inducible genes. A transcriptional target of p53, Gadd45,
      was recently found to bind to PCNA, a component of DNA replication/repair
      complexes, thereby implicating Gadd45 in DNA metabolism. Using biochemical
      assays, a role for Gadd45 in excision repair in vitro has been demonstrated.
      Antisense experiments have also indicated an in vivo role for the GADD45 gene in
      UV-irradiation survival. These discoveries establish a link between p53 and DNA
      repair through Gadd45.

PMID- 7575497
TI  - Out-of body experiences: cell-free cell death.
AB  - Apoptosis (programmed cell death) is an evolutionarily conserved cellular
      process, important for development and homeostasis. Most apoptotic cells share a
      common set of morphological and physiological characteristics that distinguish
      them from necrotic deaths. While genetic studies have indicated that these
      characteristic changes result from the activation of an endogenous 'suicide
      program', little is known about the nature of this program and the molecular
      events underlying these changes. Two recent papers describing cell-free extracts
      that reproduce several of the characteristic changes observed in apoptotic cells
      promise to make these phenomena accessible to biochemical analysis.

PMID- 7575498
TI  - Drosophila development pulls the strings of the cell cycle.
AB  - The three cycles of cell division immediately following the formation of the
      cellular blastoderm during Drosophila embryogenesis display an invariant pattern.
      Bursts of transcription of a gene called string are required and sufficient to
      trigger mitosis at this time during development. The activator of mitosis encoded
      by the string gene is a positive regulator of cdc2 kinase and a Drosophila
      homologue of the Saccharomyces pombe cdc25 tyrosine phosphatase. Evidence
      presented in a recent paper demonstrates that transcription of string, and hence
      the timing and pattern of mitosis in the postblastoderm embryo, is under complex
      developmental control. Several lines of evidence support this interpretation,
      including the analysis of string transcription in pattern formation mutants, cell
      cycle arrest mutants, and the preliminary characterization of an extensive cis
      acting regulatory region.

PMID- 7575499
TI  - Cell death suffers a TKO.
AB  - The cytokine interferon-gamma (IFN-gamma), initiates both cell cycle arrest and
      cell death in certain cell lines. Through a novel strategy of cell transfection
      with episomal vectors expressing antisense cDNAs, Deiss et al. have demonstrated
      that it is possible to isolate genes that are required for the initiation of cell
      death by the cytokine IFN-gamma. This approach, referred to as TKO, for Technical
      Knock Out, has identified several genes whose activity appears to be essential
      for the induction of apoptosis by IFN-gamma in HeLa cells. Interestingly, these
      genes appear to mediate IFN-gamma-induced apoptosis in HeLa cells, but their
      inhibition by antisense does not ameliorate the antiproliferative effects of IFN
      gamma in these cells. The clever strategy employed by these authors holds promise
      for others who wish to isolate genes required for other differentiative processes
      in cultured cell lines.

PMID- 7575500
TI  - Alkylation of DNA and its aftermath.
AB  - Current pharmacopoeias invariably refer to a category of 'alkylating drugs',
      still among the most widely used in cancer chemotherapy. They are described as
      acting through their ability to damage DNA, thus interfering with cell
      replication. Unfortunately, this mode of action implicates these drugs as
      carcinogens. Thus the early studies recalled in this essay proved to be relevant
      to our understanding of both the main problems with which cancer research
      concerns itself: the causation of cancer and possible methods of treatment of
      this group of diseases.

PMID- 7575501
TI  - Cell shape and chromosome partition in prokaryotes or, why E. coli is rod-shaped
      and haploid.
AB  - In the rod-shaped cells of E. coli, chromosome segregation takes place
      immediately after replication has been completed. A septum then forms between the
      two sister chromosomes. In the absence of certain membrane proteins, cells grow
      instead as large, multichromosomal spheres that divide successively in planes
      that are at right angles to one another. Although multichromosomal, the spherical
      cells cannot be maintained as heterozygotes. These observations imply that, in
      these mutants, each individual chromosome gives rise to a separate clone of
      descendant cells. This suggests a model in which sites for cell division form
      between pairs of sister chromosomes at the time of segregation, but are not used
      in spherical cells until further rounds of replication have taken place, thus
      ensuring clonal ('hierarchical') segregation of chromosomes into progeny cells.
      The role of the morphogenetic membrane proteins is to convert the basically
      spherical cell into a cylinder that is able to divide as soon as replication and
      segregation have been completed, and thus to maximise the number of viable cells
      per genome.

PMID- 7575502
TI  - Control of a novel adenylyl cyclase by calcineurin.
AB  - The molecular complex formed by the immunosuppressant FK506 and the immunophilin
      protein FKBP12 potently inhibits the Ca2+/calmodulin-activated protein
      phosphatase calcineurin. This mechanism appears to be common to all types of
      cell, implying that fundamental physiological modes of calcineurin regulation are
      exploited by immunosuppressants. The present paper describes a novel adenylyl
      cyclase regulated by calcineurin that contains an FKBP12-like domain and may thus
      constitute a physiologically relevant calcineurin docking site mimicked by
      immunosuppressant-immunophilin complexes. The enzyme messenger RNA is
      particularly enriched in the cerebral cortex, striatum and hippocampus, where it
      is localized to neuronal perikarya, indicative of an important role in neuronal
      function.

PMID- 7575503
TI  - Differential expression of heat shock protein 70 in well healing and chronic
      human wound tissue.
AB  - Heat shock protein 70 (hsp 70) is an important member of the heat shock protein
      family, which is induced by different forms of stress. We attempted to find out
      if hsp 70 is also involved in wound healing, which likewise resembles a stress
      situation for cells too. Therefore we collected tissue samples from well healing
      and chronic human wound tissue. We used Northern- and Western-blot analysis to
      study the expression of hsp 70. At the protein level we found a strong
      correlation between well healing wounds and high expression of hsp 70, whereas
      chronic wounds showed no or weak expression. Interestingly hsp 70 mRNA did not
      show this significant correlation, displaying a variant expression pattern in the
      same kind of wound tissue, possibly due to unknown posttranscriptional regulating
      step, which has to be investigated in further studies. To localize hsp 70 mRNA
      and protein was used insitu hybridization and immunohistochemistry. Both
      displayed an overexpression in endothelial cells of capillary vessels.

PMID- 7575505
TI  - Kinetics of nitric oxide liberation by 3,4-dihydro-1,2-diazete 1,2-dioxides and
      their vasodilatory properties in vitro and in vivo.
AB  - Derivatives of 3,4-dihydro-1,2-diazete 1,2-dioxides (DD) have been investigated
      as NO donors in vitro and in vivo. Using nitronylnitroxides as spin traps for NO,
      these compounds were shown to decompose in water solutions at physiological pH
      and temperature, producing two molecules of NO per one DD molecule. Rate
      constants of DD decomposition were found to be in the range from 10(-8) to 6.5 x
      10(-7) c-1 in water and between 3 x 10(-7) and 1.6 x 10(-5) c-1 in
      dimethylsulfoxide. In vitro experiments performed with perfused rat tail artery
      showed that some of DD derivatives are highly effective vasodilators in
      concentrations from 5 to 80 microM while standard NO donor 3-(4-morpholino)
      sydnonimine, SIN-1, does not lead to arterial vasodilation in these
      concentrations. Significant (up to 30%) decrease of systolic arterial blood
      pressure was observed in hereditary hypertensive rats (ISIAH-strain) when some of
      DD were injected intraperitoneally in doses 40-200 micrograms/kg b.w., while the
      same effect of trinitroglycerin, TNG, was found at much higher dose equal to 900
      micrograms/kg b.w.

PMID- 7575506
TI  - mRNA binding properties of wheat germ protein synthesis initiation factor 2.
AB  - The binding of protein synthesis initiation factor (eIF-) 2 to mRNA was measured
      by retention of the mRNA.eIF-2 complexes on nitrocellulose filters. The binding
      of eIF-2 to mRNA was inhibited by GDP and GTP; the inhibition by GTP was enhanced
      by the presence of Met-tRNA(i). In addition, the formation of eIF-2.GDP binary
      complex and eIF-2.GTP.Met-tRNA(i) ternary complex was inhibited by mRNA. These
      data indicate that mRNA binds to a site on eIF-2 that is the same or overlaps the
      site to which guanine nucleotides bind eIF-2. This finding strongly suggests that
      inhibition of ternary complex formation by mRNA may be the result of competition
      between mRNA and GTP and not competition between mRNA and Met-tRNA(i).

PMID- 7575504
TI  - Characterization of a distal 5'-flanking region (-2010/-630) of human GM-CSF.
AB  - The 5'-flanking region of the human GM-CSF gene was subcloned from the phagic
      clone lambda J1-16 to detect cis-elements involved in GM-CSF constitutive
      expression. We determined and sequenced an uncharacterized promoter region of
      1381 bp (-2010 to -630), named pPF2000. Putative binding sites of several
      transcriptional factors were found. Progressive deletion mutants of the PF2000
      were analyzed by measuring the linked CAT activities, in constitutive (5637) and
      inducible (PEU) GM-CSF-producing cells. A positive distal sequence (268 bp),
      between -2010 and -1742, responsible for the high constitutive expression of GM
      CSF in 5637 carcinoma cell line was found.

PMID- 7575508
TI  - Changes in the ratio of branched-chain to aromatic amino acids affect the
      secretion of albumin in cultured rat hepatocytes.
AB  - The effect of branched-chain amino acids (BCAAs) on the synthesis and secretion
      of albumin was studied in the primary cultures of rat hepatocytes. The changes in
      the normal BCAAs/aromatic amino acids (AAAs) ratio reduced the secretion of
      albumin without altering its mRNA levels. Protein-labeling and pulse-chase
      experiments showed that a low BCAAs/AAAs ratio reduced the biosynthesis, whereas
      a high ratio accelerated intracellular decay of albumin. These results suggest
      that normalization of the BCAAs/AAAs ratio improves albumin synthesis while the
      excess ratio may induce the degradation of albumin in the cells.

PMID- 7575509
TI  - pH and the cAMP-dependent protein kinase mediate growth phase induction of the
      cytochrome c oxidase subunit VI gene, COX6, in Saccharomyces cerevisiae.
AB  - Respiratory adaptation in Saccharomyces cerevisiae is a complex genetic program
      that ensures ATP synthesis in a glucose-depleted environment. ATP is generated
      during respiration by the mitochondrial electron transport chain which is induced
      by respiratory adaptation. We have studied the terminal enzyme in mitochondrial
      electron transport, cytochrome c oxidase, from S. cerevisiae. Because subunits in
      this multisubunit enzyme are coordinately regulated, we have focused upon the
      well characterized subunit VI gene, COX6. In yeast, COX6 transcription is
      regulated by several factors thought to mediate respiratory adaptation including
      growth phase induction, oxygen dependence, and glucose repression. In the present
      study, we found that in addition to these known regulators, COX6 expression also
      depends upon pH and the cAMP-dependent protein kinase which may comprise
      additional factors signaling respiratory adaptation.

PMID- 7575510
TI  - Picrotoxin is a CYP1A1 inducer in rainbow trout hepatocytes.
AB  - Picrotoxin is a CYP2B inducer in mammals (1). However, in primary cultures of
      rainbow trout hepatocytes we showed CYP1A1 gene expression to be strongly induced
      as characterized by 7-ethoxyresorufin-O-deethylase activity, immunoblots of
      CYP1A1 protein, and Northern blots of CYP1A1 mRNA. Induction of CYP1A1 in these
      cells appeared to be via the aromatic hydrocarbon (Ah) receptor as indicated by
      increased levels of Ah receptor in the nuclear extracts of picrotoxin-treated
      cells. Picrotoxin induction of CYP1A1 was blocked by actinomycin D.
      Superinduction of CYP1A1 mRNA occurred in cells treated with cycloheximide. Co
      incubation of hepatocytes with picrotoxin and a saturating concentration of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in synergistic increases in
      CYP1A1 gene expression. These results suggest that picrotoxin induction of CYP1A1
      is regulated at the level of transcription and may involve an alternative
      mechanism(s) to that of TCDD.

PMID- 7575511
TI  - Visible spectrophotometric assay, purification, and molecular properties of a
      lipoxygenase from eggplant (Solanum melongena Linne) fruits.
AB  - We purified a lipoxygenase to homogeneity from eggplant (Solanum melongena Linne)
      fruits employing the established visible spectrophotometric assay, in which the
      products of the lipoxygenase-catalyzed reaction, hydroperoxyfatty acids, oxidizes
      2,2'-azino-di-[3-ethylbenzothiazoline-(6)-sulfonic acid] diammonium salt in the
      presence of a catalyst cytochrome c to yield chromophores in the visible region.
      This allowed for the rapid detection of the lipoxygenase activity and was helpful
      in accomplishing the efficient purification of the lipoxygenase. The purified
      lipoxygenase was a monomeric enzyme with a molecular weight of 95,000, s20,w of
      5.3 S, and an isoelectric point of 4.4. The specific activity and Km value for
      the linoleate oxygenation were 7.8 mumol min-1 mg-1 and 0.8 mM, respectively, at
      25 degrees C and pH 7.0. The enzyme contained 1.3 g-atom of nonheme iron per
      enzyme.

PMID- 7575507
TI  - Positively charged surface induces discontinuous transition for the high order
      structure in duplex DNA.
AB  - Interaction of DNA molecules with solid surface was studied with single molecular
      observation by use of fluorescence microscopy. Drastic change in the conformation
      of DNA chain was induced by the interaction with the positively charged surface.
      It was found that unfolded DNA chain in aqueous solution changes into compacted
      globule accompanied with the adsorption onto the positively charged surface. A
      brief discussion is represented concerning the mechanism of the transition from
      the physico-chemical point of view.

PMID- 7575512
TI  - Carbamylation inhibits the ferroxidase activity of caeruloplasmin.
AB  - The ferroxidase activity of caeruloplasmin (EC 1.16.3.1) is an important
      antioxidant defence mechanism in man. In chronic renal failure proteins become
      carbamylated as a result of reactions with urea-derived cyanate. We have
      therefore investigated the effects of carbamylation on the ferroxidase activity
      of caeruloplasmin. Increasing degrees of carbamylation produce a progressive
      impairment of ferroxidase activity measured using o-dianisidine as substrate, and
      the ability of caeruloplasmin to load ferrous iron onto ovotransferrin is
      reduced. Carbamylation of caeruloplasmin may contribute to reduced antioxidant
      capacity in patients with renal failure.

PMID- 7575513
TI  - Sequence analysis of frog rho-crystallin by cDNA cloning and sequencing: a member
      of the aldo-keto reductase family.
AB  - rho-Crystallin is a major enzyme crystallin present in the lenses of amphibian
      species with a blocked amino terminus. In order to facilitate the determination
      of the primary sequence of this taxon-specific crystallin, cDNA mixture was
      synthesized from the poly(A)+mRNA of bullfrog eye lenses. cDNAs encoding rho
      crystallin were then amplified by polymerase chain reaction (PCR) using a new
      protocol of Rapid Amplification of cDNA Ends (RACE). PCR-amplified product
      corresponding to rho-crystallin was obtained, which was then subcloned into pUC18
      vector and then transformed into E. coli strain JM109. Plasmids purified from the
      positive clones were prepared for nucleotide sequencing by the automatic
      fluorescence-based dideoxynucleotide chain-termination method. Sequencing more
      than 15 clones containing DNA inserts coding for rho-crystallin constructed only
      one unique and complete full-length reading frame of 975 base pairs covering a
      deduced protein sequence of 324 amino acids including the universal initiating
      methionine. It shows 96, 59, 46 and 37 percent sequence similarity to another rho
      crystallin from European common frog, bovine prostaglandin-F synthase, human
      aldose reductase and human aldehyde reductase, respectively, revealing the close
      relationship between rho-crystallins from related amphibian species and its
      possible evolutionary relatedness with various aldo-keto reductases. In this
      study a phylogenetic tree for rho-crystallin and related enzymes is constructed
      based on multiple-sequence alignment program using a combination of distance
      matrix and approximate parsimony methods. We have thus established the remote
      phylogenetic relationship between rho-crystallin and some aldehyde/aldose
      reductases, which may provide a possible link for the recruitment of this
      crystallin from detoxification-related enzymes and its physiological role in
      maintaining a transparent and clear lens.

PMID- 7575514
TI  - Heteroatom substitution shifts regioselectivity of lauric acid metabolism from
      omega-hydroxylation to (omega-1)-oxidation.
AB  - In contrast to several isoforms of cytochrome P450 (including 1A1, 1A2, 2B1, 2C2,
      2C6 and 2E1), cytochrome P450 4A1 and a fusion protein derived from it, show a
      strong preference for hydroxylation of lauric acid (C12) at the less chemically
      reactive omega-CH3 group instead of the more reactive (omega-1)-CH2 group. We
      have explored the interplay of steric effects on substrate binding vs chemical
      reactivity at various substrate loci in determining the striking difference in
      regioselectivity of CYP2B1 and a 4A1-derived fusion protein, through studies with
      heteroatom substituted analogs of lauric acid, i.e., 10-methoxydecanoic acid and
      10-methylthiodecanoic acid. With both enzymes the former undergoes simple omega
      hydroxylation (giving 10-hydroxydecanoic acid and HCHO), but the latter undergoes
      facile S-oxidation at the omega-1 position instead of omega-hydroxylation. The
      dramatic shift in the regioselectivity of the fusion protein toward the thia
      analog is consistent with the greater length of C-S bonds and the greater atomic
      radius and polarizability of sulfur lone-pair electrons within an otherwise
      restrictive active site.

PMID- 7575515
TI  - Orally active and long-term acting insulin-mimetic vanadyl
      complex:bis(picolinato)oxovanadium (IV).
AB  - The blood glucose level of rats with streptozotocin (STZ)-induced diabetes has
      been found to be normalized by administration of vanadyl or vanadate complexes.
      During our investigations on the development of anti-diabetic vanadyl complexes
      with various types of coordination mode such as V-O, V-N and V-S, we found that a
      new bis(picolinato)oxovanadium (IV) complex (VPA) has a strong insulin-mimetic
      effects as evaluated by an in vitro experiments, in which the inhibition of free
      fatty acid release in isolated rat adipocytes treated with epinephrine was
      observed to be similar to that of insulin. VPA was also effective for normalizing
      the blood glucose level of STZ-induced diabetic rats when given intraperitoneally
      or orally. The serum glucose level was maintained in the normal range for about
      30 days with body weight gain after the end of oral administration of VPA for 14
      days. VPA was confirmed to be an orally active and long-term acting insulin
      mimetic vanadyl complex to treat insulin-dependent diabetes mellitus (IDDM) in
      rats.

PMID- 7575516
TI  - Stochastic behavior of organelle motion in Nitella internodal cells.
AB  - The stochastic behavior of organelles during the recovery process of protoplasmic
      streaming is investigated in Nitella internodal cells at a nanometer space
      resolution. The motions of organelles in the components parallel and
      perpendicular to the alignment of actin filaments in the cell are analysed from
      the traces of displacement of 860 organelles in 1/30s (= video rate). The
      analysis of those traces shows that the generation of motive forces to the
      organelle follows the Poisson process. Therefore, we have been able to estimate
      the step size corresponding to the single force generation as approximately 100
      nm.

PMID- 7575517
TI  - The ubiquitous VA68 isoform of subunit A of the vacuolar H(+)-ATPase is highly
      expressed in human osteoclasts.
AB  - The 67-kDa subunit A of the vacuolar-type H(+)-ATPase carries the high affinity
      ATP binding site and together with the 57-kDa subunit B forms the catalytic
      domain. Two isoforms of subunit A, VA68 and HO68, were cloned from an
      osteoclastoma cDNA library. We have analyzed their respective expression patterns
      in different tissues by RNAase A protection and in situ hybridization. The HO68
      isoform was found to be present only in the tumor originally used to construct
      the cDNA library, whereas the ubiquitous VA68 RNA isoform was detected in large
      osteoclastic cells, as well as in brian and kidney, by RNAse protection assay.
      Furthermore, we localized the strong signal observed in osteoclastoma RNA to the
      large osteoclastic cell by in situ hybridisation. These findings suggest that the
      subunit A highly expressed in human osteoclasts is the ubiquitous isoform, VA68.

PMID- 7575518
TI  - Staurosporine potentiates cAMP-mediated promoter activity of the vasoactive
      intestinal polypeptide gene in rat pheochromocytoma PC12 cells.
AB  - The potent protein kinase inhibitor staurosporine enhances cAMP-mediated
      responses in human neuroblastoma cells as represented by neurite extension and
      induction of tyrosine hydroxylase. To explore how staurosporine regulates cAMP
      signaling pathway, we examined transcriptional activity of the human vasoactive
      intestinal polypeptide (VIP) gene promoter carrying a cAMP-responsive element. In
      PC12 cells stably transfected with a reporter plasmid, staurosporine alone had
      little effect; however, in combination with forskolin or dibutyryl cAMP,
      staurosporine dose-dependently (1-50 nM) enhanced cAMP-mediated transcription
      from the VIP gene promoter, which was comparable to that maximally induced by
      cAMP plus 12-O-tetradecanoylphorbol-13-acetate. This is the first report of
      potentiation of cAMP-mediated promoter activity by staurosporine in
      neuroendocrine cells.

PMID- 7575519
TI  - Expression of a human serum albumin variant with high affinity for thyroxine.
AB  - In this study a protein expression system was used to synthesize recombinant
      human serum albumin containing a mutation that has been shown to result in
      familial dysalbuminemic hyperthyroxinemia. Equilibrium dialysis was used to
      measure the binding of this recombinant human serum albumin with thyroxine. The
      association constant determined for the binding of this human serum albumin
      variant with thyroxine was shown to be 65-fold greater than that of recombinant
      normal human serum albumin.

PMID- 7575520
TI  - Calpain inhibitor-induced apoptosis in human prostate adenocarcinoma cells.
AB  - Although it has been shown that calpains may play a positive role in causing
      apoptosis of T cells, we report here that, on the contrary, the inhibition of
      calpain-like activities can induce apoptosis in human prostate cancer cells. Two
      calpain inhibitors were used to test growth response on prostate cancer cells and
      showed remarkable cytotoxicity. The cytotoxicity was due to apoptosis as judged
      by large genomic DNA fragmentation, chromatin condensation and nuclear
      fragmentation. Furthermore, using gel band shift assays we have demonstrated that
      calpain inhibitor 1 causes a prolonged elevation of AP-1 protein activity in
      human prostate cancer cells. The elevation of AP-1 activity appears to be
      specific, because calpain inhibitor 1 only stimulates AP-1 but not AP-2 and SP-1
      activities. We postulate that the sustained increase in AP-1 activity may be
      involved in apoptosis induced in prostate cells by calpain inhibitors. Our study
      thus suggests that calpain-like activity may be a potentially therapeutic target
      for cancer.

PMID- 7575521
TI  - Visualization of agonist-induced internalization of histamine H2 receptors.
AB  - Histamine H2 receptors were tagged at the N-terminus with the eight amino acid
      Flag epitope to allow the immunological identification of the receptor peptide
      with the monoclonal anti-Flag M2 antibody. The introduction of the epitope did
      not modify the binding of several H2 ligands to the H2 receptor, nor the ability
      of histamine to stimulate the H2 receptor mediated cAMP production in HEK-293
      cells. Western blots revealed a major protein band of 57 +/- 1 kDa, whereas a
      second band of 31 +/- 1 kDa was probably the result of a proteolytic breakdown of
      the 57 kDa band. Immunofluorescence measurements of stably transfected HEK-293
      cells revealed the presence of anti-Flag-immunoreactivity in the plasma membrane.
      This immunoreactivity completely disappeared after a one hour treatment with
      histamine. The receptor internalization was reversible and blocked by the
      endocytosis inhibitor phenylarsine oxide. Forskolin did not induce H2 receptor
      internalization, indicating that histamine causes H2 receptor internalization via
      a cAMP-independent pathway.

PMID- 7575522
TI  - Differential expression of cytokine genes in cervical cancer tissues.
AB  - The expression of genes coding for inflammatory cytokine interleukin-1-alpha (IL
      1 alpha), IL-6, interferon-gamma and tumor necrosis factor-alpha from 15 normal
      cervix, 11 cervical intraepithelial neoplasia and 13 cervical cancer tissues was
      investigated. The cytokine messenger ribonucleic acids were reverse transcribed
      and amplified in the presence of biotinylated and dinitrophenylated primers.
      Amplified DNA was then captured onto streptavidin-coated microwell plate and
      quantitatively measured in a colorimetric reaction using ant-DNP antibodies
      conjugated to horse radish peroxidase. There is no change of IL-1 alpha, IL-6 and
      tumor necrosis factor-alpha gene expression in either cervical intraepithelial
      neoplasia or cervical cancer tissues. But the transcription of interferon-gamma
      gene is significantly reduced in both cervical intraepithelial neoplasia and
      cervical cancer tissue as compared to normal cervix. This study demonstrated that
      reverse transcription and quantitative polymerase chain reaction coupling to
      colorimetric microwell plate assay is a sensitive and useful method to quantitate
      multiple cytokine gene expression. Our results also suggest that cervical
      epithelial cells are capable to express cytokines and that interferon-gamma may
      play a role in the pathogenesis of cervical cancer since its reduced expression
      may influence inflammation and immunity of the cervical tissues.

PMID- 7575523
TI  - Modulation of heme oxygenase activity in rat brain and spleen by inhibitors and
      donors of nitric oxide.
AB  - The capacity of nitric oxide to activate or inhibit metalloprotein-containing
      enzymes underlies many of its biological actions. Heme oxygenase, involved in a
      variety of biological processes, does not contain heme but utilises it as a
      substrate. The substrate for nitric oxide, L-arginine (0.1-10mM), but not D
      arginine, decreased heme oxygenase activity in rat brain homogenates. The
      arginine analogue L-NAME (0.1-10mM) increased activity in the same tissue. In
      spleen homogenates where endogenous nitric oxide activity is lower than in brain,
      these compounds had no effect. The nitric oxide donor sodium nitroprusside
      (0.001mM-10mM) reduced heme oxygenase activity in both brain and spleen. These
      results suggest that biological effects attributed to modulation of nitric oxide
      synthase may act via heme oxygenase.

PMID- 7575524
TI  - Age-associated change of 8-hydroxyguanine repair activity in cultured human
      fibroblasts.
AB  - 8-hydroxyguanine (8-OH-Gua) is a major oxidative DNA damage product. Its repair
      activity was determined in the human fibroblast cell line, TIG-3, during the
      aging process. The repair activity increased in the first part of the aging
      process and decreased in the latter part. The highest repair activity was
      observed at the age of 30 PDL. These results suggest that the defense capacity
      for replication errors due to oxidative DNA damage increases greatly when the
      cells are rapidly dividing.

PMID- 7575525
TI  - Specific inhibition of vascular cell adhesion molecule-1 expression by type IV
      collagen in endothelial cells.
AB  - The effects of matrices on the expression of adhesion molecules were studied in
      cultured human umbilical cord vein endothelial cells(HUVEC). The expression of
      vascular cell adhesion molecule-1 (VCAM-1) but not of intercellular adhesion
      molecule-1 stimulated with various substances was remarkably low in HUVEC
      cultured on type IV collagen, the major component of the basement membrane,
      compared with that on type I collagen. This inhibition was observed not only at
      the protein level but also at the mRNA level. These data suggested that VCAM-1
      expression in endothelial cells is strictly regulated by the underlying basement
      membrane.

PMID- 7575527
TI  - The amino-terminal portion of pro-brain natriuretic peptide (Pro-BNP) circulates
      in human plasma.
AB  - Using an antiserum raised in rabbits to a synthetic human brain natriuretic
      peptide (BNP) N-terminal fragment [ProBNP(1-13)], a single large molecular weight
      (MW) N-terminal form of ProBNP has been identified in human plasma. Sep-pak
      extracts of plasma, drawn from patients with congestive heart failure and
      subjected to size exclusion and reverse phase high pressure liquid chromatography
      (HPLC) coupled to radioimmunoassay (RIA) revealed a single large immunoreactive
      (ir-) peak which was not detected in assays of BNP-32 [ProBNP(77-108)]. This
      material has a MW of 8600--similar to that expected for the complete N-terminal
      portion of ProBNP(1-76). Previously reported high MW BNP forms, cross reacting
      with BNP-32 antisera, were not detected using the N-terminal antisera, indicating
      that this material is unlikely to be intact ProBNP(1-108). In patients with
      congestive heart failure plasma ir-levels of N-terminal ProBNP were greatly
      raised compared to normal subjects and were up to ninefold higher than ir-BNP-32
      values.

PMID- 7575526
TI  - An embryonic alternative transcription initiation site and the 5'-upstream
      structure of mouse cardiac troponin T gene.
AB  - By specific antibody screening of a lambda ZAPII expression library, we
      identified a class of cDNAs derived from mouse cardiac troponin T (TnT) mRNA with
      long 5'-ends containing the -30 TATA sequence of the promoter. These long mRNAs
      indicated the presence of a novel upstream transcription initiation site in the
      cardiac TnT gene. Primer extension mapping of the mouse cardiac TnT mRNA
      confirmed an alternative transcription initiation site 55-base pairs upstream of
      the major initiation site. The upstream initiation site was found significantly
      more active in the embryonic/neonatal hearts. Genomic cloning and sequencing
      further revealed an 1.5-kb 5'-upstream sequence of the mouse cardiac TnT gene and
      relationships between the promoter regulatory elements and the alternative
      transcription initiation sites.

PMID- 7575528
TI  - A second, elongated, alpha 2-globin mRNA is present in reticulocytes from normal
      persons and subjects with terminating codon or poly A mutations.
AB  - With an RT-PCR procedure we have identified a second, elongated, alpha 2-globin
      mRNA in reticulocytes of normal persons and of patients with alpha-thal,
      particularly those with mutations in the terminating codon (TAA-->CAA; Hb
      Constant Spring; TAA-->TAT, Hb Pakse) or in the poly A site (AATAAA-->AATAAG).
      This type of mRNA is elongated because a result a cryptic poly A site 1048 bp
      past the terminating codon is used. Even some 5% of the alpha 2-mRNA of normal
      persons is of the elongated type. Quantitative data suggest high levels of this
      mRNA in heterozygous and homozygous carriers of poly A mutations and low levels
      in patients with the terminating codon mutations. Hematological and Hb data
      suggest that translation of these elongated mRNAs is minimal. No elongated alpha
      1-mRNA has been observed.

PMID- 7575529
TI  - Calcium destabilises Drosophila cactus protein and dephosphorylates the dorsal
      transcription factor.
AB  - The Drosophila cactus and dorsal proteins are required for the development of
      embryonic dorso-ventral polarity and probably also for the innate immune response
      of the insect. Like their mammalian counterparts (the cytoplasmic anchor protein
      I kappa B and the rel/NF kappa B transcription factors) cactus and dorsal are
      regulated at the level of nuclear localisation. We showed previously that
      increased intra-cellular calcium levels induced by the ionophore ionomycin can
      activate dorsal/cactus complexes in the Drosophila cell line SL2. In order to
      study further the activation of dorsal/cactus complexes by calcium, we have
      prepared a cell line (SLDL) in which dorsal is expressed constitutively. In this
      paper we show that in SLDL cells ionomycin induces a rapid destruction of cactus
      and dephosphorylation of dorsal. These results suggest a role for the protein
      phosphatase calcineurin in calcium mediated activation of dorsal/cactus
      complexes. They also indicate that in the resting cell constitutive
      phosphorylation of dorsal is in equilibrium with calcium dependent
      dephosphorylation.

PMID- 7575530
TI  - The protein kinase C activator Bryostatin-1 induces the rapid release of TNF
      alpha from MONO-MAC-6 cells.
AB  - Bryostatin-1 is a natural activator of protein kinase C and currently examined in
      phase I trials as anticancer agent. We found that Bryostatin-1 induced tumor
      necrosis factor alpha (TNF alpha) expression in the human cell line MONO-MAC-6.
      Using Northern blot analysis and a bioassay for the detection of the cytokine we
      observed that Bryo alone was sufficient to transiently induce mRNA synthesis and
      the rapid release of TNF alpha into the culture medium. However, the combination
      of Bryo with lipopolysaccharide resulted in a strong synergistic increase of TNF
      alpha secretion. The biologic activity of the secreted TNF alpha was amenable to
      inhibition by anti-TNF alpha antibodies. Blockade of the lipopolysaccharide
      receptor CD14 or inhibition of protein kinase C implied that both, CD14 and
      protein kinase C, are involved individually in signal transduction pathways
      leading to TNF alpha secretion from MONO-MAC-6 cells. The results demonstrate
      that Bryostatin-1 is able to induce TNF alpha secretion in human monocytes via a
      protein kinase C-dependent and CD14-independent pathway and by a mechanism which
      is most likely based on a strong increase of the TNF alpha mRNA level.

PMID- 7575531
TI  - Two novel rat guanylin molecules, guanylin-94 and guanylin-16, do not increase
      cyclic GMP production in T84 cells.
AB  - Guanylin, a 15-amino acid peptide homologue of bacterial heat-stable
      enterotoxins, is an endogenous activator of guanylate cyclase C (GC-C). We
      isolated two novel guanylin molecules from rat intestinal mucosa. They contained
      guanylin-15 at their C-termini and were identified as guanylin-94 and guanylin-16
      by amino acid sequencing and mass spectrometry. Guanylin-94 and guanylin-16 in
      total account for 85% of guanylin molecules in both the small and large
      intestine, guanylin-15 being a minor component. Rat guanylin-94 and guanylin-16
      did not increase cyclic GMP production in T84 cells. Identification of the post
      translational processing products of guanylin should provide a better
      understanding of the biosynthesis of the peptide.

PMID- 7575532
TI  - Expression and localization of glucose transporter 1 (GLUT1) in the rat oviduct:
      a possible supplier of glucose to embryo during early embryonic development.
AB  - The oviduct fluid mainly derived from the oviduct epithelium is reported to
      provide the environment necessary for embryonic development. To elucidate the
      origin of glucose in the oviduct fluid, we examined the expression and
      localization of glucose transporter 1 (GLUT1) in the rat oviduct by Northern blot
      analysis, immunoblot analysis and immunohistochemistry using both light and
      electron microscopy. Northern blot and immunoblot analyses both showed the
      presence of the GLUT1 mRNA and protein. Specific staining for GLUT1 was observed
      in the ampulla and the isthmus, but only slightly in the fimbria and the utero
      tubal junction. Staining was confined to the luminal surface of the epithelial
      mucosa. Immunoelectron microscopic analysis revealed that GLUT1 was observed only
      on the surface of the microvilli in non ciliated secretory cells, but not in
      ciliated cells. These findings suggest that GLUT1 plays an important role in the
      glucose transfer from the oviduct epithelium into the lumen and in maintaining
      the adequate glucose concentration of the oviduct fluid for embryonic development
      in rat oviduct.

PMID- 7575534
TI  - ICAM-1 expression in hepatocytes following dissociation of cell-to-cell contact
      in rats.
AB  - ICAM-1 was not detected immunohistologically in hepatocytes in normal rats, but
      detectable in centrilobular degenerative hepatocytes in carbon tetrachloride
      intoxicated rats. ICAM-1 expression was observed even in normal hepatocytes
      following liver perfusion with Hank's balanced salt solution at a flow rate of
      4.2 mL/g liver weight/min or with the same solution containing collagenase or
      EGTA at the physiological flow rate (1.4 mL/g liver weight/min). Such expression
      was also observed when liver perfusion was performed after pretreatment of rats
      with cycloheximide. On electron microscopy, ICAM-1 was exclusively stained on
      hepatocyte plasma membrane that was detached from the plasma membrane of adjacent
      hepatocytes. ICAM-1 mRNA and ICAM-1 protein were detected in hepatocytes freshly
      isolated from normal rats. Thus, ICAM-1 expression in degenerative hepatocytes as
      well as in hepatocytes following liver perfusion can be assumed to result from
      dissociation of cell-to-cell contact.

PMID- 7575533
TI  - Galactose stabilizes various missense mutants of alpha-galactosidase in Fabry
      disease.
AB  - The effect of galactose on alpha-galactosidase missense mutants causing Fabry
      disease was investigated in the COS-1 cell expression system and lymphoblasts.
      Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and
      amount in COS-1 cells cultured with galactose. Another mutant without catalytic
      activity, C142Y, did not show any changes. In lymphoblasts cultured with
      galactose, the enzyme activity increased significantly in four classical Fabry
      patients with the respective mutations, A156V, L166V, G260A and G373S, and in
      three atypical Fabry patients with the respective mutations, Q279E, R301Q and
      M296I. Such an increase was not observed in the other four classical Fabry
      patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests
      that many missense mutations in the alpha-galactosidase gene causing Fabry
      disease allow the expression of catalytically active mutant enzymes regardless of
      the clinical phenotype, which are rapidly degraded under physiological conditions
      and stabilized by galactose.

PMID- 7575535
TI  - The carboxy-terminal 18 amino acids of the measles virus hemagglutinin are
      essential for its biological function.
AB  - The hemagglutinin (HA) glycoprotein encoded by measles virus (MV) is a type II
      integral membrane protein that is expressed at the infected cell surface. Genes
      encoding wild-type MV HA as well as two mutant HA proteins shortened at their
      carboxy-termini by either 18 (HA delta 18O) or 223 (HA delta 223) amino acids
      were constructed and studied in a transient expression system in COS cells. Under
      nonreducing conditions, assembly of HA delta 18 into homodimers was diminished
      while HA delta 223 remained in a monomeric form. Hemadsorption assays revealed
      that neither mutant was functional at the cell surface. These studies show that
      the carboxy-terminal ectodomain of the HA protein is essential to its proper
      folding and assembly into homodimers while its carboxy-terminal 18 amino acids
      are essential for the hemadsorption (receptor-binding) function of the protein.

PMID- 7575536
TI  - Polymorphisms and probable lack of mutation in a human mutT homolog, hMTH1, in
      hereditary nonpoliposis colorectal cancer.
AB  - The human MTH1 gene, a homolog of the E. coli mutator gene mutT, encodes 8-oxo
      dGTPase that degrades a mutagenic substrate for DNA synthesis. To determine
      whether this gene is associated with hereditary nonpolyposis colorectal cancer
      (HNPCC), we examined the hMTH1 sequence in 32 HNPCC cases by means of polymerase
      chain reaction-single strand conformation polymorphism and sequencing analyses.
      Three different DNA variants were identified in normal and the corresponding
      tumor DNA. The first variant, a G to A transition at codon 83, changes valine to
      methionine and was detected in 9 HNPCC cases. The same change was detected in 5
      of 30 unrelated healthy individuals, suggesting that it is not associated with a
      marked HNPCC predisposition. The second variant is a silent C to T transition at
      codon 119. Another C to T transition at 31 bp upstream of the beginning of exon 4
      was also found. However, specific mutations in hMTH1 were detected in neither
      normal nor tumor cells from HNPCC patients. These results indicate that hMTH1 is
      not directly involved in HNPCC.

PMID- 7575537
TI  - Reversible inhibition of NADPH-cytochrome P450 reductase by alpha-lipoic acid.
AB  - NADPH-cytochrome-P450 reductase both purified from rat hepatic microsomes and
      involved in microsomal fraction was inactivated by treatment with alpha-lipoic
      acid. Since alpha-lipoic acid contains disulfide bond, it reacts with SH-groups
      of the reductase via the reaction of thiol-disulfide exchange resulting in the
      loss of the enzyme reducing activity. NADP+ completely protected reductase from
      the inactivation. The modification of reductase was reversible: the modified
      enzyme was partially reactivated with dithiothreitol and dihydrolipoic acid in
      the case when cytochrome c was used as a substrate of reductase. In the case when
      inorganic substrate, K3Fe(CN)6, was used for assay the activity of modified
      reductase no reactivation was observed. It was found that the order of the
      reaction of inactivation of membrane-bound microsomal reductase is equal to 1.2
      +/- 0.2, which is in an agreement with pseudo-first order kinetics, and the
      second-order-rate constant of 26 M-1min-1. The results have shown that well known
      therapeutic agent alpha-lipoic acid is an efficient inhibitor of both purified
      and microsomal reductase.

PMID- 7575538
TI  - Improved recombinant tandem expression of translation initiation factor IF2 in
      RNASE E deficient E. coli cells.
AB  - The prokaryotic translation initiation factor IF2 exists in a varying number of
      nested forms in different species. In E. coli three natural forms exist, IF2
      alpha, IF2 beta and IF2 gamma differing only in the N-terminal: IF2 beta and IF2
      gamma lack 158 and 165 amino acid residues, respectively, as compared to IF2
      alpha. We have earlier shown that the smaller forms of IF2 are not the result of
      a specific proteolysis of IF2 alpha, but produced from individual translation
      initiation sites in the mRNA. However it has not been known whether the
      expression in E. coli of IF2 beta and IF2 gamma is dependent on or related to a
      posttranscriptional processing of the polycistronic nusA operon, containing infB,
      the gene for IF2. Here we have used S1 mapping to study the existence of such
      mRNA processing in the region between the initiation sites for IF2 alpha and IF2
      beta/IF2 gamma. The results show a Ribonuclease E cleavage site at position +200
      in the infB mRNA between the translation initiation sites. However, studies of
      the overexpression of the different forms of IF2 show that the relative
      expression of IF2 alpha and IF2 beta/IF2 gamma is independent of RNase E
      activity. Thus E. coli exhibits a true tandem translation of intact infB mRNA
      with multiple in-frame translation initiation sites resulting in gene products of
      different sizes. An additional observation is a significant increase in the level
      of overexpression of IF2 in cells devoid of RNase E activity. We conclude that
      due to lack of RNase E activity, the amount of plasmid-transcribed infB mRNA
      available for translation is accumulated, resulting in an elevated amount of
      recombinant IF2. This observation may have a more general application within the
      field of recombinant protein production and expression efficiency.

PMID- 7575539
TI  - Dexamethasone regulates obese expression in isolated rat adipocytes.
AB  - An obese (ob) gene product, expressed specifically in adipose tissues, regulates
      energy balance. Here we report adipocytes in adipose tissue actually express ob
      mRNA and that a synthetic glucocorticoid (dexamethasone) regulates expression of
      the ob gene. Addition of 100 nM dexamethasone to isolated rat adipocytes rapidly
      induced a 4-8 fold increase in ob mRNA. This increase in ob mRNA level was
      apparent within 1 h, and reached a maximum at about 7 h after stimulation. The
      dexamethasone-stimulated increase of ob mRNA was only partially blocked by
      protein synthesis inhibitors cycloheximide (20 micrograms/ml) or anisomycin (200
      microM). This suggests that new protein synthesis is not necessarily required for
      the observed dexamethasone-stimulated increase in ob mRNA.

PMID- 7575540
TI  - Flavonoids as scavengers of nitric oxide radical.
AB  - Flavonoids are a group of naturally occurring compounds used, e.g., in the
      treatment of vascular endothelial damage. They are known to be excellent
      scavengers of oxygen free radicals. Since the nitric oxide radical (.NO) probably
      plays a role in this pathology, the .NO scavenging capacity of the flavonoids was
      determined. It was found that the flavonoids are very potent .NO scavengers. The
      anthocyanidins were found to be more effective scavengers than the
      hydroxyethylrutosides, which correlated with their therapeutic activity. The
      values of their scavenging rate constants are only 30 times less active than the
      very potent endogenous .NO scavenger haemoglobin. It is speculated that .NO
      scavenging plays a role in the therapeutic effect of the flavonoids.

PMID- 7575541
TI  - A newly identified GPI-anchored arginine-specific ADP-ribosyltransferase activity
      in chicken spleen.
AB  - Arginine-specific ADP-ribosyltransferase activity was detected in chicken spleen
      membrane fraction and the activity was extracted by phosphatidylinositol-specific
      phospholipase C but not by 1 M NaCl or 1% Triton X-100. The transferase activity
      extracted from the spleen membrane was thiol-independent and was not inhibited by
      200 mM NaCl. Zymographic analysis of the transferase, under non-reducing
      conditions, showed two forms of active bands corresponding to a molecular mass of
      46 and 42 kDa. Thus, the presence of this novel arginine-specific ADP
      ribosyltransferase, anchored to the membrane through glycosylphosphatidylinositol
      and different from previously cloned chicken transferases, AT1 and AT2, is being
      given further attention.

PMID- 7575542
TI  - Phosphofructo-1-kinase: role of charge neutralization in the active site.
AB  - Previous studies of Escherichia coli phosphofructo-1-kinase have shown that
      mutation of Asp 127 lowers kcat by 5 orders of magnitude. As shown here,
      introduction of a second mutation (R252Q) that neutralizes a positive charge in
      the active site increases activity of D127S by 100 fold, suggesting that part of
      the effect of the Asp mutation may be attributed to non-specific charge
      interactions. This conclusion is supported by the fact that the R252Q mutant
      shows a pH dependence that is the reverse of the wild type enzyme, whereas the
      double mutant has a pH dependence that resembles that of wild type enzyme,
      although somewhat attenuated.

PMID- 7575543
TI  - Activation of cyclin E-dependent kinase by DNA-damage signals during apoptosis.
AB  - Preexposure of HL-60 cells to a DNA-damaging agent, cytosine arabinoside (Ara-C),
      dramatically induced the levels of H1 kinase activities associated with cyclin E
      (CycE-H1K) but not cyclin A. This induction was cell cycle-independent and
      accompanied by loss of cell viability, a late event in apoptosis. When an Ara-C
      resistant variant of HL-60 cells were treated with Ara-C at a low concentration,
      neither CycE-H1K nor apoptosis were observed. Both events were induced in the
      resistant cells but only after treatment with Ara-C at a much higher
      concentration for a longer period. The DNA-damage-induced CycE-H1K is proposed to
      be involved in a late apoptosis checkpoint.

PMID- 7575545
TI  - Instability at the H-ras minisatellite is associated with the spontaneous
      abortion of the embryo.
AB  - Recently we have shown that microsatellite instability (MI) is a detectable
      phenomenon in aborted embryonic tissues. In the present study we investigated if
      instability is also detectable in a minisatellite located at the 3'-end of the H
      ras proto-oncogene, affecting either the repetition number of the 28-bp core
      generating larger or smaller alleles or its sequence creating a detectable
      restriction fragment length polymorphism (RFLP). Among 30 aborted embryonic
      tissues, alterations at the repetition number of the core were found in 3 (10%)
      while point mutations were detected in 7 (23%) cases. These results indicate that
      structural alterations of the H-ras minisatellite may be associated with the
      rejection of the embryo.

PMID- 7575546
TI  - Advanced Maillard reaction and crosslinking of corneal collagen in diabetes.
AB  - Diabetes mellitus is associated with a number of changes in the cornea. These
      include increased corneal autofluorescence, thickening and enhanced endothelial
      cell permeability. In this study we have investigated the biochemical changes of
      corneal collagen due to advanced Maillard reaction and lysyl oxidase mediated
      crosslinking in diabetes. Advanced Maillard reaction was estimated by collagen
      bound fluorescence and pentosidine. Hydroxypyridinium (a trifunctional
      fluorescent crosslink) was estimated as an index of lysyl oxidase mediated
      crosslinking. Both fluorescence (p < 0.05) and pentosidine were present at higher
      levels in diabetic corneas when compared with age-matched control corneas.
      Hydroxypyridinium levels were only marginally increased in diabetes. These
      results suggest that corneal collagen is modified in diabetes by advanced
      Maillard reaction and that such modifications may have effect on corneal
      thickening, endothelial cell permeability and other abnormalities of the cornea
      in diabetes.

PMID- 7575544
TI  - Spontaneous calcium waves without contraction in cardiac myocytes.
AB  - Spontaneous Ca2+ waves were visualized in quiescent cardiomyocytes loaded with
      the Ca(2+)-sensitive fluorescent probe, Fluo-3, and imaged by laser confocal
      microscopy. No sarcomere shortening was detected during wave propagation. This
      type of Ca2+ waves began at the periphery or in a central region of a myocyte and
      propagated the length of the cell in one or two directions. The average velocity
      of wave propagation was 32 microns/sec and the estimated concentration of Ca2+
      oscillated from 124, at the bottom, to 311 nM, at the pick of the wave. Ca2+
      waves were not confined to a single cell but could spread from cell to cell.
      These results describe a type of spontaneous Ca2+ waves which does not induce a
      contractile response in cardiomyocytes.

PMID- 7575547
TI  - Membrane potential and intercellular calcium during glucose challenge in mouse
      islet of Langerhans.
AB  - The present work was undertaken to study the effects of the addition and removal
      of glucose on the calcium concentration of the intercellular space [Ca2+]o of
      islets of Langerhans. The removal of glucose hyperpolarize the beta-cell membrane
      to near- 60 mV and induced a biphasic response in [Ca2+]o. On the other hand, the
      addition of glucose (11 mM) depolarized beta-cell, inducing a biphasic electrical
      activity and concomitant changes in the [Ca2+]o. During the continuous membrane
      electrical activity, which characterized the first phase of glucose evoked
      biphasic response, the [Ca2+]o decreased. In the second phase, the [Ca2+]o
      displayed an oscillatory behavior concomitantly with the membrane potential.

PMID- 7575548
TI  - Type I inositol-triphosphate receptor gene is alternatively spliced in human
      cerebral arteries.
AB  - Three distinct genes encode the three isoforms of the inositol triphosphate (IP3)
      receptor (type I, II and III) expressed in brain. Coupling domain of neuronal
      type I receptor contains a 117 nucleotide insert located between two cyclic AMP
      dependent protein kinase (PKA) phosphorylation consensus sequences. By contrast,
      in nonneuronal tissues this insert is removed by alternative splicing. Neuronal
      tissue and cerebral arteries share the same embryologic origin. The present study
      was designed to characterize alternative splicing of the type I IP3 receptor gene
      in vascular tissue of human brain. Total RNA was isolated from human basilar and
      middle cerebral arteries and cerebellum. One microgram of total RNA was reverse
      transcribed. First strand cDNA was obtained and used as a template in polymerase
      chain reaction (PCR). PCR products were subcloned and sequenced. Specific mRNA
      for type I and II receptors were detected in human cerebral arteries. In vascular
      tissue, a short transcript was expressed indicating that the type I receptor was
      alternatively spliced. In contrast, only nonspliced isoform was detected in
      cerebellum. These results suggest that alternative splicing corresponds to
      differences in regulation of cerebrovascular and neuronal IP3 receptors.

PMID- 7575549
TI  - The primary structures of rat ribosomal proteins L4 and L41.
AB  - The amino acid sequences of the rat 60S ribosomal subunit proteins L4 and L41
      were deduced from the sequences of nucleotides in recombinant cDNAs. Ribosomal
      protein L4 has 421 amino acids; the molecular weight is 47,280. L41 is the
      smallest ribosomal protein; it has 25 amino acids and a molecular weight of
      3,454. Hybridization of the cDNAs to digests of nuclear DNA suggests that there
      are 7 to 8 copies of the L4, and 9 to 12 of the L41, genes. The mRNA for L4 is
      about 1,500 nucleotides in length and that for L41 about 500 nucleotides. The 5'
      noncoding sequence of the L4 cDNA is exceptional in that it has, in addition to a
      short polypyrimidine sequence at the 5' end, a second stretch of 15 consecutive
      pyrimidines near the site of initiation of translation. The 3' noncoding sequence
      of the L41 mRNA is unusual in that it is at least 246 nucleotides long. Rat L4
      and L41 are related to ribosomal proteins from other eukaryotes.

PMID- 7575550
TI  - Serum withdrawal induces apoptotic cell death in Ki-ras transformed but not in
      normal differentiated thyroid cells.
AB  - Thyroid cells transformed by the Kirsten-ras oncogene become tumorigenic in
      syngeneic animals. Their growth is no longer dependent on TSH but becomes
      dependent on serum. Combining morphological and biochemical evidence, we show
      that serum withdrawal induces apoptotic cell death in Kirsten and Harvey-ras
      transformed thyroid cell. On the other hand, neither serum nor TSH withdrawal
      induce apoptosis in differentiated FRTL-5 cells. The induction of apoptosis by
      serum withdrawal is rapid and not triggered at a specific phase of the cell
      cycle. We suggest that induction of apoptosis following growth factor deprivation
      is an additional important characteristic, besides TSH-independence for growth
      and dedifferentiation, of the thyroid transformed phenotype.

PMID- 7575551
TI  - Fast kinetic studies of plasmid DNA transfer in intact yeast cells mediated by
      electropulsation.
AB  - Intact yeast cell Electrotransformation process was investigated. It is a two
      step process. The plasmid must be pre-mixed and present in contact with the cells
      during the pulse. During the millisecond field pulse, plasmid DNA is associated
      to the envelope. It therefore crosses the membrane by a process which lasts
      several seconds as shown by its sensitivity to a post pulse addition of DNase.
      Electrotransformation is not supported by an electrophoretic transfer due to the
      external field nor by a free diffusion across the electropermeabilized envelope.
      DNA is first bound during the field pulse and then is transferred by a still
      unknown active process due to cell metabolism.

PMID- 7575552
TI  - Selective inhibition of steroid 5 alpha-reductase isozymes by tea epicatechin-3
      gallate and epigallocatechin-3-gallate.
AB  - Inhibitors of 5 alpha-reductase may be effective in the treatment of 5 alpha
      dihydrotestosterone-dependent abnormalities, such as benign prostate hyperplasia,
      prostate cancer and certain skin diseases. The green tea catechins, (
      )epigallocatechin-3-gallate and (-)epicatechin-3-gallate, but not (-)epicatechin
      and (-)epigallocatechin, are potent inhibitors of type 1 but not type 2 5 alpha
      reductase. (-)Epigallocatechin-3-gallate also inhibits accessory sex gland growth
      in the rat. These results suggest that certain tea gallates can regulate androgen
      action in target organs.

PMID- 7575553
TI  - Dependence and reversal of nitric oxide production on NF-kappa B in silica and
      lipopolysaccharide-induced macrophages.
AB  - In this report the differential regulation of NF-kappa B and nitric oxide (NO)
      was investigated in the mouse macrophage cell line RAW 264.7 following exposure
      to a mineral dust (silica) and/or an endotoxin (Lipopolysaccharide, LPS). The
      results indicated that silica and LPS can significantly induce the activation of
      NF-kappa B as well as elicit enhanced production of NO in RAW 264.7 cells as part
      of an early inflammatory response mechanism. A 24-hour time-course study showed
      that NO release from these cells continued to increase following the initial
      stimulus by LPS or silica. In contrast, activation of NF-kappa B was maximal at 6
      hours and then showed a steady decline to 24 hours. The production of NO was
      suppressed by protease inhibitor and antioxidant, both of which block the
      activation of NF-kappa B. Surprisingly, the use of an NO synthase inhibitor
      resulted in an enhancement of NF-kappa B activation. These findings suggest that
      NO produced in macrophage cells in response to an inflammatory stimulus like
      silica or LPS my be linked to a negative feedback role on the activation of NF
      kappa B.

PMID- 7575554
TI  - Estrogen increases endothelial nitric oxide by a receptor-mediated system.
AB  - To determine the mechanism of the antiatherosclerotic effect of estrogen, we
      investigated the effect of estrogen on endothelial nitric oxide synthase (NOS-3).
      Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12)-10(
      8) M) over 8 hours significantly enhanced the activity of NOS-3 in endothelial
      cells of cultured human umblical vein (HUVEC) and of bovine aortas (BAEC). 17
      beta-estradiol also enhanced the release of nitric oxide (NO) as measured by an
      NO selective meter and NO2-/NO3-, metabolites of NO, from endothelial cells.
      Western blot showed a similar effect of 17 beta-estradiol on NOS-3. The estrogen
      receptor antagonists, tamoxifen and ICI182780, each inhibited the effect of 17
      beta-estradiol by 80%. The effect of 17 beta-estradiol gradually decreased in
      cells beyond the 10th passage and was not significant in cells beyond the 16th
      passage. Immunocytochemistry showed the existence of estrogen receptor in HUVEC
      and BAEC (less than 5 passages) and the sparseness of the existence in BAEC
      beyond the 16th passage. Estrogen increases NOS-3 via a receptor-mediated system,
      and estrogen receptor, which appeared to be altered by cell senescence, could be
      important in the release of NO from endothelium.

PMID- 7575555
TI  - Adhesion-inducible DNA synthesis regulated by tyrosine
      phosphorylation/dephosphorylation.
AB  - Non-malignant rat liver epithelial cell line BRL was reported to adhere to a
      substrate by fibronectin. DNA synthesis of these cells was induced by adhesion to
      a substrate by fibronectin, while DNA synthesis in non-adhered cells was not
      observed. These results indicated that DNA synthesis in BRL cells is inducible by
      the cell adhesion signaling. Adhesion-inducible DNA synthesis was strongly
      inhibited by Herbimycin A. In contrast, vanadate showed the tendency to promote
      adhesion-inducible DNA synthesis. These results suggest that DNA synthesis caused
      by the cell adhesion in these cells was regulated by both phosphorylation and
      dephosphorylation at tyrosine residue.

PMID- 7575557
TI  - In vivo effect of prednisolone on release of leukotriene C4 in eosinophils
      obtained from asthmatic patients.
AB  - We investigated the release of leukotriene C4 from eosinophils of asthmatic
      patients who were treated with or without intravenous prednisolone. The mean
      level of LTC4 in the supernatant of A23187-stimulated eosinophils obtained from
      asthmatic patients during an attack was significantly lower with intravenous
      prednisolone than without prednisolone treatment. Findings suggest that
      intravenous prednisolone inhibits the release of LTC4 from the eosinophils of
      asthmatic patients by acting on these cells in vivo.

PMID- 7575556
TI  - Effects of long-term omeprazole treatment on adult rat gastric mucosa-
      enhancement of the epithelial cell proliferation and suppression of its
      differentiation.
AB  - Effects of long-term omeprazole treatment on the process of epithelial cell
      proliferation and differentiation in the adult rat gastric mucosa were
      investigated. Animals were treated with omeprazole (25 mg/kg body weight/day) for
      28 days to induce anacidity in the stomach. The treatment induced a marked
      decrease in the number of chief cells in the gastric mucosa and at the same time
      an increase in that of immature pepsinogen-producing cells expressing class III
      mucin. This was accompanied by a decrease to 60% and 10% of the control values in
      the mucosal levels of pepsinogen and its mRNA, respectively. Moreover, the
      expression of cathepsin E in surface mucous cells was reduced. Cell proliferation
      studies revealed that the rate of bromodeoxyuridine-labeled cells was increased
      by omeprazole. The above-described changes were reversed by cessation of the
      treatment and they were not caused by the omeprazole-treatment at a dose which
      does not induce anacidity in the stomach. These results suggest that long-term
      omeprazole treatment reversibly increases the epithelial cell proliferation and
      suppresses its differentiation in the adult rate gastric mucosa probably by
      altering the acidic environment specific for the stomach.

PMID- 7575558
TI  - Ferrochelatase binds the iron-responsive element present in the erythroid 5
      aminolevulinate synthase mRNA.
AB  - Ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, binds an
      iron-responsive element (IRE) present in the 5'untranslated region of the mRNA
      for erythroid 5-aminolevulinate synthase, the first enzyme of the heme
      biosynthetic pathway. This IRE-binding activity of ferrochelatase may play a
      critical role in the regulation of heme biosynthesis in differentiating
      erythrocytes.

PMID- 7575559
TI  - Eye CNG channel is modulated by nicotine.
AB  - The cyclic-nucleotide gated channel (CNG channel) of the rod outer segment of the
      retina (ROS) has its closed conformation stabilized by nicotine. Calcium and cGMP
      influence the Ki of the channel current to nicotine. Calcium lowers the Ki and
      cGMP increases it, giving a range of Ki between 10(-11) and 10(-8) M.

PMID- 7575560
TI  - Development of a rapid approach to identification of tyrosine phosphorylation
      sites: application to PKC delta phosphorylated upon activation of the high
      affinity receptor for IgE in rat basophilic leukemia cells.
AB  - In rat basophilic leukemia cells (RBL-2H3) activation of the high affinity
      receptor for IgE induces tyrosine phosphorylation of PKC delta. We carried out
      solid phase synthesis of 15 amino acid long oligopeptides corresponding to the
      sequences around each of the 19 tyrosine residues in PKC delta. Only three
      oligopeptides, corresponding to tyrosine 52, 155, and 565, were phosphorylated
      when exposed to lyn kinase. Single mutants in each of these three tyrosine
      residues of PKC delta were prepared. Upon expression in the RBL-2H3 cells, only
      the mutant in tryosine 52 showed abolition of the IgE-antigen induced tyrosine
      phosphorylation.

PMID- 7575561
TI  - Reduced neurofibromin content but normal GAP activity in a patient with
      neurofibromatosis type 1 caused by a five base pair duplication in exon 12b of
      the NF1 gene.
AB  - We screened a total of 87 unrelated patients with neurofibromatosis type 1 (NF1)
      for mutations in exons 11, 12a, and 12b of the NF1 gene using temperature
      gradient gel electrophoresis (TGGE). A novel mutation (1998insCCTCT) was found in
      exon 12b. The 5-bp duplication comprising nucleotides 1994 to 1998 is predicted
      to lead to a truncated protein product lacking three quarters of its C-terminal
      sequence including the entire GTPase-activating protein-(GAP)-related domain.
      This mutation is associated with a reduction by 50% of the detectable amount of
      neurofibromin found in this patient. Despite the reduced level of neurofibromin
      cellular GAP activity was normal, which suggests that defects in other functions
      of the neurofibromin molecule may be important in the pathogenesis of NF1.

PMID- 7575562
TI  - Loss of membrane integrity and inhibition of type-I iodothyronine 5'
      monodeiodinase activity by fenvalerate in female mouse.
AB  - The possible involvement of lipid peroxidation (LPO) in the fenvalerate-induced
      thyroid dysfunction with special reference to type I 5'-monodeiodinase (5'-D)
      activity has been worked out. Fenvalerate (40, 80 and 120 mg/kg body weight)
      enhanced LPO in biomembranes of liver and kidney leading to a decrease in
      membrane integrity. 5'-D activity and serum concentration of triiodothyronine
      (T3) were reduced by the highest dose. Serum thyroxine (T4) concentration was
      decreased in all the three fenvalerate-treated groups, indicating the sensitivity
      of thyroid gland to this pesticide. A marginal increase in T4 concentration in
      highest dose-treated group compared to that of the lower one supports the view
      that the monodeiodination of the phenolic ring of T4 is inhibited by fenvalerate.
      We suggest the possible inactivation of 5'-D by the generated free radicals in
      pesticide-treated animals.

PMID- 7575564
TI  - Cyclic GMP stimulates growth hormone release in rat anterior pituitary cells.
AB  - In this study, the role of cGMP on growth hormone (GH) release was examined using
      a static monolayer culture prepared from dispersed rat anterior pituitary cells.
      Treatment with 8-bromo-cGMP (1 microM to 1 mM) stimulated GH release up to 3.8
      fold in a concentration-dependent manner. Elevating cGMP with nitroprusside or
      the C-type natriuretic peptide was also effective in stimulating GH release. The
      increase in GH release by cGMP-elevating agents occurred without a concomitant
      increase in cAMP. Unlike cAMP which increased intracellular Ca2+ concentration, 8
      bromo-cGMP caused a small reduction in intracellular Ca2+ concentration. Taken
      together, these results indicate that i) cGMP appears to be another mechanism
      that regulates GH release, ii) activation of cytosolic or membranous guanylyl
      cyclase is equally effective in stimulating GH release; and iii) the cGMP-induced
      GH release appears to be through a mechanism distinct from that of cAMP.

PMID- 7575563
TI  - Improved gene expression by a modified bicistronic retroviral vector.
AB  - We have previously described the construction of a bicistronic retroviral vector
      using the picornavirus internal ribosome entry site (IRES), which allows two
      genes expression simultaneously from a single transcript. This vector transcribes
      RNA efficiently; however, in some cases the levels of protein production are low.
      In this report, we further modified the bicistronic vector by abolishing the
      functional viral gag initiation codon that is retained in the vector at 5' to the
      first initiation codon of transduced gene. Five different genes, human
      interleukin 2 (hIL-2), human interleukin 4 (hIL-4), human granulocyte macrophage
      stimulating factor (hGM-CSF), herpes simplex virus thymidine kinase (HSV-tk)
      gene, and hepatitis C virus (HCV) core gene (C190), were tested on this modified
      vector for gene transfer and expression. Our results demonstrated that the new
      bicistronic vector greatly increased the protein levels when compared with the
      original one. As the RNA levels and splicing patterns from these two vectors
      remained similar, the improvement was most likely resulted from the increased
      translational efficiency.

PMID- 7575565
TI  - HMG-I binds to GATA motifs: implications for an HPFH syndrome.
AB  - We have examined binding of the nuclear protein HMG-I to the human gamma-globin
      promoter. We find that HMG-I binds preferentially to the more 3' of a pair of
      GATA motifs in the gamma-globin promoter; this paired motif is bound by the
      erythroid factor GATA-1. A naturally occurring mutation (-175 T-C) in the area
      bound by HMG-I results in overexpression of gamma-globin in adult red blood cells
      (HPFH) and up-regulation of the gamma-globin promoter in in vitro expression
      assays; HMG-I does not bind to this mutant sequence. A survey of GATA motifs from
      other globin cis-elements demonstrates HMG-I binding to most of them. These
      findings implicate HMG-I in the HPFH phenotype; we speculate that it may
      participate in the formation of multiprotein complexes that regulate globin gene
      expression.

PMID- 7575566
TI  - Both RNA polymerase III and RNA polymerase II accurately initiate transcription
      from a human U6 promoter in vitro.
AB  - The promoter of vertebrate U6 small nuclear RNA genes consists of a TATA box and
      a snRNA proximal sequence element (PSE), and the combination of these two
      elements directs RNA polymerase III transcription. We detected RNA polymerase II
      transcription as well as pol III transcription from the human U6 promoter in a
      HeLa nuclear extract. The pol II-specific transcription was independent of the
      PSE and dependent on the presence of the TATA box. Both pol III- and pol II
      specific transcription were stimulated by addition of recombinant TATA-binding
      protein (TBP). We conclude that both pol III and pol II preinitiation complexes
      can assemble on the U6 promoter in vitro and could compete during the bona fide
      process in the cell.

PMID- 7575568
TI  - Nitric oxide regulates IL-8 expression in melanoma cells at the transcriptional
      level.
AB  - We investigated the role of nitric oxide (NO) in the expression of interleukin-8
      (IL-8) in the human melanoma cell line, G361. Three NO donors, 3
      morpholinosydnonimine hydrochloride (SIN-1), S-nitroso-N-acetylpenicillamine
      (SNAP), and S-nitroso-L-glutathione (SNOG), all caused an increase in both IL-8
      protein secretion and promoter activity. Truncation of the promoter showed that
      101 bp of the 5' flanking region proximal to the transcription start site are
      sufficient for the response to NO. Furthermore, mutation of the NF-kappa B and NF
      IL-6 binding sites led to a significant decrease in NO-stimulated promoter
      activity. The nitric oxide synthase inhibitor, NG-amino-L-homoarginine (NAHA),
      inhibited TNF-alpha-stimulated IL-8 promoter activity by 60%. Addition of excess
      L- but not D-arginine partially reversed the NAHA-mediated inhibition. These
      results demonstrate that NO is an endogenous regulator of IL-8 production in G361
      melanoma cells.

PMID- 7575567
TI  - Involvement of CD45 in dexamethasone- and heat shock-induced apoptosis of rat
      thymocytes.
AB  - CD45 is a transmembrane tyrosine-specific phosphatase which participates in
      lymphoid cell signal transduction during T cell activation, as well as in
      intrathymic negative and positive selection. In mammals, this molecule exhibits a
      variety of isoforms of different molecular weight, whose roles have still to be
      fully elucidated. We report here that apoptosis of rat thymocytes after in vitro
      dexamethasone and heat shock treatment was accompanied by an early significative
      increase of cells expressing CD45RC, the high molecular weight isoform of CD45
      molecule. The same phenomenon was observed in thymocytes derived from in vivo
      dexamethasone-treated rats. However, the increase of CD45RC+ cells was not
      apparently characteristic of cells undergoing apoptosis, as the same phenomenon
      was also observed in rat thymocytes induced to proliferate by Concanavalin A. On
      the whole, these results suggest that CD45 modulation can be added to the list of
      early molecular events, such as the increased expression of genes (ornithine
      decarboxylase), proto-oncogenes (c-fos, c-jun, c-myc) and activation of
      transcription factors (AP-1, NFkB), we previously demonstrated in the same
      experimental model to occur and to be shared by these two apparently opposite
      biological processes, i.e., cell proliferation and apoptosis, both likely
      depending on a complex balance of protein phosphorylation and dephosphorylation.

PMID- 7575569
TI  - Identification and purification of a 90-kDa membrane-bound endogenous inhibitor
      of multicatalytic proteinase from human erythrocytes.
AB  - We have identified and purified an endogenous inhibitor of multicatalytic
      proteinase (MCP) from human erythrocyte membranes. The inhibitor showed a
      molecular mass of 90 kDa on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The inhibitor protein was purified from the
      erythrocyte membranes using Heparinagarose and hydroxylapatite chromatography and
      the size exclusion on a Biogel A 1.5 m column in the presence of high salt. The
      90-kDa protein inhibited all three peptidase activities of MCP; trypsin-like,
      chymotrypsin-like and peptidyl glutamyl peptide hydrolyzing (PGPH). However, it
      failed to cause any significant inhibition of caseinolytic activity of MCP,
      suggesting that the regulation of proteinase and peptidase activities is
      distinct. The inhibition of the chymotrypsin-like activity was noncompetitive.
      The results suggest that the 90-kDa inhibitor protein may be an important
      regulator of membrane-bound MCP.

PMID- 7575570
TI  - Structural analysis of invasion plasmid antigen D (IpaD) from Shigella flexneri.
AB  - Invaison plasmid antigen D (IpaD) and water-extracted outer-membrane proteins
      (OMPs) from Shigella flexneri were used to investigate some of the structural
      relationships of this pathogen's invasions. Extracellular presentation of the
      three invasion plasmid antigens (Ipa) B, C, and D is required for the S. flexneri
      invasive phenotype; however, little is known of the structural properties of
      these essential virulence components. Biochemical data suggest IpaB, C, and D
      present in S. flexneri OMPs from soluble protein complexes and IpaD may be able
      to form large homopolymeric complexes.

PMID- 7575571
TI  - Inactivation of DNA polymerase alpha-primase by acrolein: loss of activity
      depends on the DNA substrate.
AB  - We have utilized acrolein as a model compound to examine the biochemical behavior
      of chemically-modified DNA polymerase alpha-primase complex (pol alpha). We have
      found that acrolein irreversibly inactivates the DNA synthetic capacity of pol
      alpha polymerase in a time- and concentration-dependent manner. Double-stranded
      DNA protects pol alpha polymerase from inactivation when present during acrolein
      exposure, but single-stranded DNA, dATP and ATP do not. Strikingly, the activity
      of pol alpha polymerase is strongly dependent upon the DNA substrate utilized to
      assay catalytic activity after exposure to the aldehyde. The primase activity of
      pol alpha is also inactivated by exposure to acrolein, but the observed rate of
      inactivation is slower than that seen for DNA synthesis. Competitive labeling
      studies with [14C] iodoacetamide suggest that acrolein inactivation of the enzyme
      is mediated through the modification of protein sulfhydryl groups.

PMID- 7575572
TI  - Transcriptional activation of ori lambda regulates lambda plasmid replication in
      amino acid-starved Escherichia coli cells.
AB  - Replication of lambda plasmid DNA is inhibited in amino acid-starved wild type
      Escherichia coli cells (i.e., during the stringent response), whereas it proceeds
      for several hours in relA mutants (i.e., during the relaxed response). It was
      demonstrated previously that ppGpp-mediated inhibition of transcription starting
      from the pR promoter is responsible for inhibition of lambda plasmid replication;
      RNA polymerase function is indispensable for replication of lambda plasmid DNA
      during the relaxed response. The replication is carried out by the heritable
      replication complex containing the lambda O protein which is protected from
      proteases by other elements of this complex. Here we demonstrate that the
      replication is dependent on DnaG (primase) function. Thus, in amino acid-starved
      cells, lambda plasmid replication requires RNA polymerase function only for
      transcriptional activation of ori lambda. We also present evidences that the
      replication is dependent on the function of DNA gyrase. On the basis of these
      findings and other recent reports, we demonstrate a model of the regulation of
      lambda plasmid replication driven by the inherited replication complex. It seems
      that transcriptional activation of ori lambda indirectly triggers the initiation
      of lambda plasmid DNA replication at least during the relaxed response.

PMID- 7575573
TI  - Essential role of NF-kappa B activation in silica-induced inflammatory mediator
      production in macrophages.
AB  - In this report, we demonstrate that NF-kappa B, a ubiquitous transcription
      factor, plays an essential role in silica-induced inflammatory mediator
      production in the mouse macrophage cell line RAW 264.7. Compared to the effect of
      lipopolysaccharide (LPS), silica mediated a stronger activation of NF-kappa B
      p50/p50 homodimer at early phase of poststimulation. Furthermore, activation of
      NF-kappa B by silica and LPS appears to be mediated by different signal
      transduction pathways. Both silica and LPS increased mRNA expression in these
      cells for cyclooxygenase II, inducible nitric oxide synthase, tumor necrosis
      factor-alpha and interleukin-1 alpha. This expression was attenuated along with
      the inhibition of NF-kappa B activation.

PMID- 7575574
TI  - Copper binding to the N-terminal tandem repeat region of mammalian and avian
      prion protein: structural studies using synthetic peptides.
AB  - Using CD spectroscopy we have investigated the effect of Cu2+ on the secondary
      structure of synthetic peptides Octa4 and Hexa4 corresponding to tetra-repeats of
      the octapeptide of mammalian PrP and the hexapeptide of chicken PrP. In addition,
      fluorescence spectroscopy was used to estimate the dissociation constants (Kd),
      of Cu2+ binding by both peptides. Both peptides exhibited unusual CD spectra,
      complicated by the high proportion of aromatic residues, revealing little
      secondary structure in aqueous solution. Addition of Cu2+ to Hexa4 induced an
      increase in random coil to resemble Octa4. The fluorescence of both peptides was
      quenched by Cu2+ and this was used to calculate Kd's of 6.7 microM for Octa4 and
      4.5 microM for Hexa4. Other divalent cations showed lesser effects on the
      fluorescence of the peptides.

PMID- 7575575
TI  - The T-box near the zinc fingers of the human vitamin D receptor is required for
      heterodimeric DNA binding and transactivation.
AB  - The T-box mediates binding of retinoid X receptor (RXR) homodimers to DNA while
      the P- and D-box in the zinc fingers of steroid hormone receptors play roles in
      DNA-binding specificity and homodimerization, respectively. We investigated the
      function of these elements in the human vitamin D receptor (hVDR) by mutating a
      Lys-Glu pair of amino acids in the T-box, and by altering the P- and D-boxes to
      the corresponding residues of the glucocorticoid receptor (GR). The T-box mutant
      hVDR displayed attenuated vitamin D responsive element (VDRE) binding in the
      presence of RXR and was severely compromised in transcriptional activation. In
      contrast, GR P/D-box mutant hVDRs bound to the rat osteocalcin VDRE and elicited
      near normal transcriptional activation. The T-box mutant uniquely exhibited
      dominant negative properties, highlighting the significance of this region of
      hVDR for heterodimeric transcriptional activation.

PMID- 7575576
TI  - Molecular cloning, sequence, and expression patterns of the human gene encoding
      CCAAT/enhancer binding protein alpha (C/EBP alpha).
AB  - The human gene encoding the transcription factor C/EBP alpha was isolated from an
      umbilical cord genomic library screened by low stringency hybridization. Two
      overlapping clones were characterized by restriction enzyme analysis and included
      13.2 kb of the C/EBP alpha locus. The entire gene and 471 bp of the promoter were
      sequenced. The human C/EBP alpha gene is 2783 bp long and encodes a 356 amino
      acid long protein, which is the same in length as for rat C/EBP alpha. Compared
      to rat C/EBP alpha, there are two insertions of two amino acids and one deletion
      of four. The amino acid similarity between the two proteins is over 92%. The
      human C/EBP alpha gene was found to be expressed at the highest levels in
      placenta. High expression was also found in liver, lung, skeletal muscle,
      pancreas, small intestine, colon and in peripheral blood leukocytes. However, the
      expression was undetectable or very low in brain, kidney, thymus, testis and
      ovary. These results show that the human C/EBP alpha gene is expressed in a
      tissue restricted manner.

PMID- 7575577
TI  - Spin trapping agent, phenyl N-tert-butyl nitrone, inhibits induction of nitric
      oxide synthase in endotoxin-induced shock in mice.
AB  - Spin trapping agent, phenyl N-tert-butyl nitrone (PBN) significantly reduces
      mortality due to lipopolysaccharide (LPS)-induced shock in Balb/c mice as had
      previously been shown in rats. We hypothesized that PBN decreases mortality by
      directly or indirectly inhibiting nitric oxide (NO) generation. Therefore, we
      determined the effect of PBN administration on LPS-induced NO generation in mice.
      NO generation was monitored in the mouse liver after administration of LPS by an
      in vivo NO-spin trapping, followed by ex vivo EPR measurement. When the mice was
      treated with PBN 0.5hr before LPS administration, NO generation in the liver was
      reduced by 80%. However, when PBN was given 3hrs after LPS, NO generation did not
      change. Both pre- or post-administration of NO synthase (NOS) inhibitor, NG
      monomethyl-L-arginine inhibited the NO generation. Western blotting of inducible
      NOS (iNOS) in mouse liver cytosol obtained from PBN-pretreated animals
      demonstrated a decreased expression of iNOS, indicating the reduction in NO
      generation was caused by the decrease in the amount of enzyme present but not by
      the inhibition of iNOS enzyme activity per se.

PMID- 7575579
TI  - Spatial and temporal Ca2+ signalling in articular chondrocytes.
AB  - Stimulation of pig articular chondrocytes with either bradykinin, fetal calf
      serum or the Ca(2+)-ATPase inhibitor thapsigargin induced increases of the
      cytosolic Ca2+ concentration. By computerized videoimaging, the spatial and
      temporal aspects of the Ca2+ signal were revealed at single cell level. The cell
      response depended on Ca2+ release from intracellular stores without significant
      contribution of Ca2+ influx. A great heterogeneity in the cell population was
      found with respect to the Ca2+ storage ability. The Ca2+ response initiated in a
      discrete subcellular region and then spread in a nondecremental fashion to
      involve the whole cytosol. Such a behaviour was independent of the stimulus
      applied, thus suggesting a functional heterogeneity of the intracellular Ca2+
      stores involved. In the region from which the response started, local Ca2+ spikes
      were recorded, revealing a spatially restricted pulsatile activity.

PMID- 7575578
TI  - Embryonic expression and DNA-binding properties of zebrafish pax-6.
AB  - Zebrafish pax-6 (pax[zf-a]) and its murine homologue are structurally and
      functionally related to the Drosophila paired box gene eyeless, a master control
      gene for eye development. This report details the zebrafish pax-6 embryonic
      expression pattern both at the mRNA and protein level. Transcripts are first
      detected in the presumptive forebrain and hindbrain regions of the neural plate.
      After formation of the neural keel, Pax-6 protein accumulates within the same two
      domains. Expression is also observed in the optic vesicles and lens placodes,
      confirming that the Pax-6 protein is expressed in those areas of the eye where it
      is assumed to control differentiation. The relative DNA-binding affinity of the
      zebrafish Pax-6 protein to different categories of Pax recognition sites is
      shared with the murine homologue.

PMID- 7575580
TI  - Effects on CYP27 mRNA expression in rat kidney and liver by 1 alpha, 25
      dihydroxyvitamin D3, a suppressor of renal 25-hydroxyvitamin D3 1 alpha
      hydroxylase activity.
AB  - The production of 1 alpha,25-dihydroxyvitamin D3 is known to be down regulated by
      1 alpha,25-dihydroxyvitamin D3 itself. It was recently shown that liver
      mitochondrial sterol 27-hydroxylase CYP27, present also in kidney, catalyzes 1
      alpha-hydroxylation of 25-hydroxyvitamin D3. Treatment of vitamin D-deficient
      rats with a single i.v. dose of 1 alpha,25-dihydroxyvitamin D3 resulted in a
      marked suppression of CYP27 mRNA in kidney. The effects were not as pronounced as
      for CYP24. Liver CYP27 was not affected to the same extent. The results of the
      present communication indicate a coordinate regulation of CYP27 mRNA levels and
      25-hydroxyvitamin D3 1 alpha-hydroxylase activity by 1 alpha,25-dihydroxyvitamin
      D3 in rat kidney.

PMID- 7575581
TI  - Detection of a beta-parvalbumin isoform in the mammalian inner ear.
AB  - A small, acidic calcium-binding protein (CBP-15) has been detected in the guinea
      pig organ of Corti, the auditory receptor organ. The apparent molecular weight
      (15,000) and very low isoelectric point (pI approximately 3.1) suggest that CBP
      15 is a beta-parvalbumin isoform. Consistent with this hypothesis, CBP-15
      exhibits extreme homology to the mammalian oncofetal parvalbumin called
      oncomodulin. Sequence data have now been obtained for 30 residues in the N
      terminal third of CBP-15. Identity with oncomodulin is observed at all 30
      positions. This finding could necessitate revision of the assumption that
      postnatal mammals utilize a single alpha-parvalbumin isoform in muscle and
      nonmuscle settings alike.

PMID- 7575582
TI  - Effect of lipopolysaccharide treatment in vivo on tissue expression of
      argininosuccinate synthetase and argininosuccinate lyase mRNAs: relationship to
      nitric oxide synthase.
AB  - Since arginine is the only physiological substrate for the NO synthase reaction,
      regulation of arginine availability could determine the cellular rate of NO
      production. We investigated whether lipopolysaccharide (LPS) treatment in vivo
      would alter tissue expression of mRNAs for argininosuccinate synthetase (AS) and
      argininosuccinate lyase (AL), the net action of which is to convert citrulline to
      arginine. Concomitant with the induction of NO synthase mRNA, injection of LPS
      into the rats elicited an increase in AS and AL mRNA levels in the tissues. In
      contrast with modest increases in the abundance of AS and AL mRNA in lung and
      heart, a marked increase in levels of AS and AL mRNA in the kidney occurred. The
      liver, whether or not treated with LPS, contained high levels of mRNA for AS and
      AL which are components of the urea cycle. Findings suggest that an increase in
      the renal capacity to convert citrulline to arginine could play a key role in NO
      formation in vivo when arginine becomes limiting.

PMID- 7575583
TI  - Peroxisomes contain delta 3,5,delta 2,4-dienoyl-CoA isomerase and thus possess
      all enzymes required for the beta-oxidation of unsaturated fatty acids by a novel
      reductase-dependent pathway.
AB  - The presence of delta 3,5,delta 2,4-dienoyl-CoA isomerase in peroxisomes was
      demonstrated by determining the subcellular distribution of this enzyme in rat
      liver. The peroxisomal and mitochondrial forms of the isomerase exhibit similar
      chain length specificities and they are homologous as indicated by the
      recognition of the peroxisomal 66-kDa enzyme by an antiserum raised against the
      mitochondrial 32-kDa isomerase. This report demonstrates that peroxisomes contain
      all enzymes required for the beta oxidation of unsaturated fatty acids with odd
      numbered double bonds by a novel pathway in which double bonds are reductively
      removed by the NADPH-dependent 2,4-dienoyl-CoA reductase.

PMID- 7575584
TI  - Increase in cystine transport activity and glutathione level in mouse peritoneal
      macrophages exposed to oxidized low-density lipoprotein.
AB  - The transport of cystine has been investigated in mouse peritoneal macrophages
      incubated with oxidized low-density lipoprotein (oxi-LDL; low-density
      lipoprotein, LDL). The transport activity for cystine was potently induced by oxi
      LDL but not by native or acetylated LDL. The response of the cells to oxi-LDL was
      dependent on the extent of oxidative modification of LDL. The transport activity
      for other amino acids was not induced by oxi-LDL. GSH content increased in
      macrophages incubated with oxi-LDL and this increase was accounted for by the
      induction of the cystine transport activity because the increase was completely
      blocked by glutamate or homocysteate which shared the transport system for
      cystine and thus inhibited the uptake of cystine competitively.

PMID- 7575585
TI  - C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase
      activity.
AB  - The Hepatitis C Virus (HCV) NS3 protein contains amino acid motifs of a serine
      proteinase, a nucleotide triphosphatase (NTPase), and an RNA helicase based on
      amino acid sequence analysis. Proteinase and NTPase activities of the HCV NS3
      protein were reported by several investigators. Here, we show that the
      recombinant HCV NS3 protein purified from a T7 promoter and His-tag expression
      system possesses an RNA helicase activity. The recombinant HCV NS3 protein
      consists of 466 amino acids from the carboxy terminal of a HCV NS3 open reading
      frame and 25 additional residues from the vector. The recombinant HCV NS3 protein
      was purified by metal-binding chromatography. The helicase activity requires ATP
      and divalent cations such as Mg2+ and Mn2+. The helicase activity was abolished
      by monoclonal antibody specific to the HCV NS3 protein.

PMID- 7575586
TI  - Purification and characterization of a paralytic polypeptide from larvae of
      Myrmeleon bore.
AB  - A toxic substance was purified from larvae of the antilion, Myrmeleon bore, by
      DEAE Sephacel and Phenyl Superose column chromatography. The substance was a
      large polypeptide with a molecular weight of about 165-167 kDa. Its paralytic
      activity measured by injection against German cockroaches was about 130 times
      higher than that of tetrodotoxin on a molar basis.

PMID- 7575587
TI  - Long-PCR of the ANP gene and PCR-SSCP analysis of the proximal promoter region of
      the ANP gene in patients with aldosterone producing adenoma.
AB  - Previous studies have shown a significant association between allelic frequencies
      at the ANP gene locus and aldosterone responsiveness to angiotensin in
      aldosterone-producing adenoma (APA). We searched for any gross insertions or
      deletions in the ANP gene in APA and any associations between allelic frequencies
      at the Hpa II and Sca I RFLP sites within the ANP gene and angiotensin-responsive
      and unresponsive APA and normal subjects. We also searched for possible point
      mutations in the promoter region of the ANP gene (-595 to transcription start
      site) in peripheral blood and tumor DNA from 59 patients with APA and in
      peripheral blood DNA from 39 normal subjects by polymerase chain reaction and
      single strand conformation polymorphism (PCR-SSCP) analysis. No large alterations
      in the ANP gene were observed, and no difference in allelic frequencies at the
      RFLP sites were seen between the two tumor subtypes, angiotensin-responsive and
      angiotensin-unresponsive APA, or between the APA group and normal subjects. SSCP
      analysis, however, did reveal mutations in the promoter region of the ANP gene (
      375 to -595) in both peripheral blood and tumor DNA from 8 of 59 (14%) patients
      with APA, compared with only one of 39 normal controls (2.6%). This study
      suggests that alterations in the proximal promoter region of the ANP gene in APA
      may be important in the regulation of ANP transcription and may be involved in
      the underlying pathophysiology of aldosterone-producing adenoma in at least some
      patients.

PMID- 7575588
TI  - Modulation of P-glycoprotein and mdr1b mRNA expression by growth factors in
      primary rat hepatocyte culture.
AB  - P-glycoproteins encoded by members of the mdr gene family function as membrane
      situated transport proteins, isoforms of which are involved in conferring a form
      of multidrug resistance by participating in secretion of various xenobiotics. In
      primary rat hepatocytes maintained in serum-free culture, accumulation of
      immunodetectable P-glycoprotein and mdr1b mRNA occurred in a time-dependent
      manner and was accompanied by a substantial decrease in retention of the mdr1
      substrate rhodamine 123. However, incubation of cells with epidermal growth
      factor (EGF) or with insulin-like growth factor I (IGF-I) markedly enhanced time
      dependent accumulation of P-glycoprotein and mdr1b mRNA. Furthermore, EGF-treated
      cells exhibited decreased intracellular rhodamine 123 retention, an effect
      partially inhibited by the chemosensitizer verapamil. These data suggest that an
      increase in (a) functional transporter(s) eliciting transport of mdr1 substrates
      occurs under EGF.

PMID- 7575590
TI  - Physico-chemical modeling of the role of free radicals in photodynamic therapy.
      III. Interactions of stable free radicals with excited photosensitizers studied
      by kinetic ESR spectroscopy.
AB  - The loss of paramagnetism of the stable free radical 4,4'-di-tert.-butyl-
      diphenyl-1-nitroxy during illumination of the photosensitizer meso
      tetrahydroxyphenyl chlorine by light above 620 nm in the absence of oxygen has
      been followed by kinetic ESR spectroscopy. Addition of the spin trap alpha-(4
      pyridyl-1-oxide)- N-tert.-butyl-nitrone reduces the initial rate of the
      disappearance of the free radical enabling to separate triplet-doublet
      interactions from processes between radicals stemming from the triplet sensitizer
      and the stable free radical. Kinetic treatment of the mechanism suggested yielded
      the rate constant of the triplet-doublet interaction proceeding via electron
      transfer being about 6% of the rate constant of the overall interaction including
      both energy transfer and electron transfer.

PMID- 7575591
TI  - Binding of vitamin D to low-density-lipoprotein (LDL) and LDL receptor-mediated
      pathway into cells.
AB  - The present study was undertaken to identify serum components other than vitamin
      D-binding proteins that bind to 1,25(OH)2 D3, and its analog. The binding rate of
      1,25(OH)2 D3, 22-oxa-1,25(OH)2D3 (OCT) or 25(OH) D3 to total lipoprotein(TLP)
      represented 16.7%, 4.65%, and 3.11% of total counts added, respectively.
      Polyacrylamide gel electrophoresis of the TLP revealed that 1,25(OH)2 D3 and OCT
      were associated with LDL. The binding studies of OCT-bound LDL to the fibroblasts
      showed specific pathway to the cells mediated by LDL-receptor. These findings may
      have important implications in understanding the mechanisms of the diverse
      biological actions of 1,25(OH)2 D3 and in designing a novel delivery system for
      vitamin D analogs.

PMID- 7575592
TI  - Comparative study of bone marrow induced by purified BMP and recombinant human
      BMP-2.
AB  - Into a calf muscle pouch in Wistar rats, 50 micrograms purified bone
      morphogenetic protein (pBMP) or 50 micrograms recombinant human bone
      morphogenetic protein-2 (rhBMP-2) was implanted using atelopeptide type I
      collagen solution (CL) as a carrier. Three weeks later bone and bone marrow were
      induced in both groups. These induced bone and bone marrow were studied
      histologically. In the pBMP+CL group (n = 5), rich bone matrix and little bone
      marrow were observed. There was no fatty marrow or angioid tissue observed. In
      the rhBMP-2+CL group (n = 5), bone matrix and rich marrow including fatty marrow
      and angioid tissue were observed around and among the bony trabeculae. It was
      suggested that a "self-supporting bone organ" was induced.

PMID- 7575589
TI  - Generation of resistance to the diphenyl ether herbicide acifluorfen by MEL
      cells.
AB  - The diphenyl ether herbicide acifluorfen has been shown to act by inhibition of
      the terminal enzyme of the protoporphyrin biosynthetic pathway,
      protoporphyrinogen oxidase (E.C. 1.3.3.4) (PPO), in plant and animal cells. In
      the present study we show that long term maintenance of murine erythroleukemia
      (MEL) cells in acifluorfen, which is normally toxic to these cells at 5 microM
      concentration, results in cells that grow at a near normal rate in 100 microM
      acifluorfen. Acifluorfen resistant cells do not have increased levels of PPO
      activity, nor does the PPO made by these cells have increased resistance to
      acifluorfenin, but these cells accumulate porphyrin and have elevated levels of
      heme. Data is presented that suggests the resistance of these MEL cells to
      acifluorfen may be attributable to induction of a cytochrome P450(s).

PMID- 7575593
TI  - The human erythrocyte membrane contains a novel 12-kDa inositolphosphate-binding
      protein that is an immunophilin.
AB  - A 12-kDa inositolphosphate-binding protein has been identified as a component of
      the human erythrocyte membrane. Its robust peptidylprolyl cis-trans isomerase
      activity that is strongly inhibited by the immunosuppressant drugs FK506 and
      rapamycin indicates that it is an immunophilin belonging to the FKBP class. The
      finding that its peptidylprolyl cis-trans isomerase activity is also strongly
      inhibited by nanomolar concentrations of the second messengers inositol 1,4,5
      trisphosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4) suggests that
      IP3 and IP4 could be physiological ligands for this membrane-associated
      immunophilin.

PMID- 7575594
TI  - Effect of cAMP and cGMP on endothelin-stimulated tyrosine phosphorylation in
      rabbit platelets.
AB  - Activation of platelets by different agents results in the increased tyrosine
      phosphorylation of several substrate proteins. Thus, the effect of endothelin-1
      on the stimulation of tyrosine phosphorylation in rabbit platelets can be
      inhibited by preincubation with forskolin, which increase the cAMP level.
      However, incubations of platelets with 8-Bromo-cGMP showed lower inhibitory
      effect. Forskolin produced a dose-dependent inhibition on three different protein
      substrates, with an IC50 of approximately 12.8, 4.0 and 8.0 microM in the three
      molecular mass ranges of 50, 60 and 100-200 kDa, respectively. These results show
      that the endothelin-stimulated tyrosine phosphorylation in rabbit platelets can
      be regulated by a novel pathway of platelet signal transduction in which the cAMP
      level could be more relevantly involved than cGMP in some molecular mass ranges
      of tyrosine phosphorylated proteins.

PMID- 7575595
TI  - Biology of enterostatin. II. Development of enzyme-linked immunosorbentassay
      (ELISA) for enterostatin (Val-Pro-Asp-Pro-Arg), the procolipase activation
      peptide.
AB  - Enterostatins belong to a family of pentapeptides (e.g., Val-Pro-Asp-Pro-Arg in
      pig, horse, dog, and rat; Ala-Pro-Gly-Pro-Arg in human and chicken; and Val-Pro
      Gly-Pro-Arg in rat) derived from the amino-terminus of procolipase after the
      action of trypsin. Pharmacologic studies with Val-Pro-Asp-Pro-Arg have suggested
      a role for this peptide in appetite regulation and pancreatic insulin secretion.
      Studies into the distribution of enterostatins or the role of endogenous peptides
      have not been possible due to the lack of a suitable method for enterostatin
      assay. To this end, we raised a highly specific antibody and developed an enzyme
      linked immunosorbent assay for Val-Pro-Asp-Pro-Arg. Using the newly developed
      assay we have shown the presence of Val-Pro-Asp-Pro-Arg-like immunoreactivity
      (2455 +/- 440 pmol/g) in the rat brain.

PMID- 7575596
TI  - Early gene signalling-dependent and -independent induction of apoptosis in Ramos
      human B cells can be inhibited by over-expression of Bcl-2.
AB  - We have previously shown that calcium ionophore-induced apoptosis of Ramos human
      B cells is preceded by the induced expression of early response genes, implying a
      requirement for new gene expression in this mode of programmed cell death. We
      have found in the present studies that inhibitors of macromolecular synthesis,
      cycloheximide and actinomycin D, are also potent inducers of apoptosis in the
      same Ramos cell model. These drugs trigger apoptosis through apparently early
      gene signalling-independent pathways. Although different mechanisms for induction
      of apoptosis exist in Ramos cells, enforced over-expression of Bcl-2 protects
      cells from apoptosis induced in response to different agents, demonstrating that
      Bcl-2 blocks a final common pathway for programmed cell death in the Ramos cell
      model.

PMID- 7575600
TI  - Structure of prejunctional receptor binding analog of human neuropeptide Y dimer
      ANA-NPY.
AB  - Human neuropeptide Y (NPY) analog ANA-NPY or [L17, Q19, A20, A23, L28, L31]NPY
      (13-36)-amide binds weakly to postjunctional receptors to raise blood pressure
      but binds tightly to prejunctional receptors to inhibit neurotransmitter release.
      ANA-NPY forms a well-conserved anti-parallel helical structure overlapping E23
      Y36 with strong amphipathic character. The C-terminal portions of the monomers
      are better defined than the N-terminal ends. The N-terminal helices extend only
      from D16-E23/L24. The prejunctional receptor-specific binding site is confined
      within the C-terminal helices while the residues responsible for partial binding
      to the postjunctional receptors are located in the more disordered N-terminal
      segments.

PMID- 7575597
TI  - Room temperature ESR spectra of Rhus vernicifera laccase and derivatives.
AB  - Although both the type 1 and type 2 coppers of Rhus vernicifera laccase are fully
      ESR detectable at 77 K, only 30% of the type 2 copper are in the cupric form at
      room temperature. The residual 70% of the type 2 copper was easily transformed
      into the ESR detectable form by irradiating the resting enzyme with microwave of
      200 mW. The enzyme activity did not change by the irradiation with high-powered
      microwave, indicating that the type 2 copper can be in both the ESR detectable
      and ESR undetectable forms in solution. The room temperature ESR spectra of the
      type 2 copper-depleted laccase and of the azide-bound type 3 copper signals were
      also measured at room temperature and compared with those at 77 K.

PMID- 7575601
TI  - Cell specific differences in DNase I hypersensitivity between the two promoters
      of the rat glucokinase gene.
AB  - Glucokinase (GK) gene transcription occurs in the liver and the beta cell of the
      endocrine pancreas where it is subject to different modes of regulation. This is
      accomplished largely through the use of two linked, cell-specific promoters
      separated by at least 12 kbp. We have used DNase I hypersensitivity to explore
      the chromatin structure surrounding the two promoters in cells that express
      either the liver or beta cell form of the GK gene, as well as cells that do not
      express GK. In RIN38 cells, a beta-cell-derived cell line, hypersensitive sites
      are detected over both the proximal and distal promoters. In liver,
      hypersensitive sites are present in the proximal promoter but not the distal
      promoter. Interestingly, in H4IIEC3 cells, a hepatoma cell line that has lost the
      ability to express GK, hypersensitive sites are also found in the proximal
      promoter but not the distal promoter.

PMID- 7575599
TI  - High level expression of birch pollen profilin (Bet v 2) in Escherichia coli:
      purification and characterization of the recombinant allergen.
AB  - Up to 20% of the population in industrialized countries suffer from type I
      allergic symptoms (rhinitis, conjunctivitis, and bronchial asthma). The cDNA
      coding for birch pollen profilin, a highly conserved cross-reactive allergen and
      actin-binding protein was expressed in Escherichia coli. Upon induction with IPTG
      up to 30 mg recombinant profilin per liter culture could be obtained. A single
      step purification protocol based on the high affinity of profilin to poly-(L
      proline) Sepharose was used to obtain large amounts of soluble and pure
      recombinant birch profilin. Recombinant birch pollen profilin specifically bound
      IgE, elicited dose dependent histamine release from patients basophils and could
      be used for skin prick testing without toxic effects. The results indicate that
      by using purified recombinant profilin, specific diagnosis of type I allergy
      might be improved.

PMID- 7575598
TI  - Functional and structural interactions of the Rab5 D136N mutant with xanthine
      nucleotides.
AB  - Rab5 is a Ras-related GTPase which regulates endosomal fusion. The D136N mutant
      of Rab5, which was predicted to switch specificity from guanine to xanthine
      nucleotides, was expressed in E. coli, extracted with urea, purified by column
      chromatography, and refolded by stepwise dialysis against buffer containing XDP.
      The purified protein bound xanthine nucleotides with considerably higher affinity
      than guanine nucleotides. In vitro prenylation of the mutant protein was highly
      dependent on xanthosine diphosphate. In contrast, both the wild type and mutant
      proteins were protected from proteolysis equally well by non-cognate and cognate
      triphosphate nucleosides at high concentration. The D136N Rab5 mutant appears to
      be a valuable reagent in conjunction with xanthine nucleotides for the study of
      protein-nucleotide interactions in systems in which multiple GTPases are active,
      although interactions with non-cognate nucleotides should be evaluated if they
      are present at high concentration.

PMID- 7575602
TI  - Impaired tumor phenotypes in class II major histocompatibility complex antigen
      inducible cells originated from human lung adenocarcinoma.
AB  - The class II major histocompatibility complex (MHC) antigens play important roles
      in T cell activation and are thought to be involved in tumor development. Using
      anti-class II antibodies with interferon gamma (IFN-gamma), we have here selected
      class II MHC antigen positive cancer cells from the human lung adenocarcinoma
      cell line A549, which is originally negative (> 95%) for the antigens. A part of
      the class II antigen-positive cells presented a flat morphology, which was not
      observed in the parental A549 cells. Class II antigen expression in these flat
      cells was IFN-gamma inducible; there was a correlation between the inducibility
      and phenotypic changes. A class II antigen-inducible flat subline restored the
      ability of contact inhibition and anchorage-dependent growth as well as lost
      tumorigenicity in athymic mice.

PMID- 7575603
TI  - Ligand-induced conformational changes in the mineralocorticoid receptor analyzed
      by protease mapping.
AB  - The human mineralocorticoid receptor (MR) binds the agonists aldosterone and
      cortisol and the antagonist progesterone with a comparably high affinity. We used
      limited proteolysis of human MR synthesized by in vitro translation to detect
      structural alterations induced by these different endogenous ligands. Steroid
      binding induces a conformational change within the receptor protein. This
      structural alteration renders a fragment of MR resistant to proteolysis. Agonists
      and antagonist vary in how well they protect the MR fragment against proteolysis.
      But the two agonists also differ in their ability to protect, indicating that
      agonists and antagonists, but also different agonists, may induce distinct
      conformational changes. Ligand-independent removal of MR-associated heat-shock
      proteins induces no detectable structural change but completely prevents ligand
      binding of MR.

PMID- 7575604
TI  - Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent
      proteolysis and its degradation product.
AB  - In most cells, the inactive dimeric NF-kappa B complexes are retained in the
      cytoplasm by binding to a group of inhibitory proteins. I kappa B. In response to
      extracellular stimuli, I kappa B is rapidly phosphorylated and degraded, thus,
      liberating the active NF-kappa B. To investigate the mechanisms involved, we have
      developed a cell-free system to study the degradation of the prototype I kappa B
      protein, I kappa B alpha. In this in vitro assay, ubiquitin, proteasome
      containing S100 fraction and ATP are required for the proteolysis of I kappa B
      alpha. Both bound and free forms of I kappa B alpha isolated from intact cells
      can be degraded through this pathway. We also identified polyubiquitinated I
      kappa B alpha molecules and N-terminal truncated I kappa B alpha degradation
      product(s) both in vivo and in vitro. We conclude that the inactivation of I
      kappa B alpha occurs through a series of processes including phosphorylation, ATP
      dependent ubiquitin conjugation and proteasome-mediated proteolysis.

PMID- 7575605
TI  - Enzymatic analysis of cell surface lactosaminyl glycans by flow cytometry.
AB  - Cell surface expressed lactosaminyl glycans were determined on live cells by flow
      cytometry using a sialyltransferase mediated labeling procedure. Fluorescent CMP
      sialic acid and Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase were applied to
      probe expression of acceptor glycans on untreated or sialidase pretreated
      erythrocytes. After enzymatic fluorescence labeling, erythrocytes were treated
      with endo-beta-galactosidase or trypsin to distinguish polylactosaminyl- and
      complex-type glycans. The expression of lactosaminyl sequences on cord- was 20%
      lower than on adult cells. After sialidase treatment fluorescence incorporation
      on both cell types increased twofold compared to untreated cells indicating a low
      sialylation extent. A recombinant alpha 2,3-sialyltransferase was preferentially
      labeling polylactosaminyl glycans. Taking advantage of the different fine
      specificity as determined here, alpha 2,6- and alpha 2,3-sialyltransferase can be
      applied to distinguish certain types of lactosaminyl glycans.

PMID- 7575606
TI  - G-protein modulation of alpha 1A (P/Q) type calcium channel expressed in GH3
      cells.
AB  - GH3 cell lines stably expressing alpha 1A channel were established and the
      modulation of this channel by G-protein through membrane-delimited pathways were
      studied. Wild type GH3 cells were found to express omega-conotoxin MVIIC (MVIIC)
      sensitive Ca2+ current but this component was different from the alpha 1A channel
      because of its susceptibility to G-protein modulation, suggesting MVIIC also
      blocks channels other than P/Q type. Alpha 1A channel expressed in GH3 cells
      showed slowing of activation and reduction of current amplitude by the
      application of carbachol. Both of these effects were pertussis toxin (PTX)
      sensitive and voltage dependent. alpha 1A channels were also found to be
      modulated through a PTX insensitive pathway, the modulations observed were
      similar to those in the PTX sensitive pathway. The results further suggest that
      these two effects are governed by a different mechanism in both PTX sensitive and
      insensitive pathways.

PMID- 7575607
TI  - Increased expression of keratinocyte growth factor in human pancreatic cancer.
AB  - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor
      (FGF) group of heparin-binding polypeptides. In the present study we sought to
      determine whether KGF is expressed in human pancreatic cancers. Using reverse
      transcriptase polymerase chain reaction (RT-PCR), a cDNA fragment of KGF was
      cloned and used to analyze Northern blots of RNA isolated from normal and
      cancerous human pancreatic tissues. Seven of 16 (44%) pancreatic cancer samples
      revealed significant overexpression of the 2.4 kilobase KGF mRNA transcript by
      comparison with the normal pancreas. Northern blot analysis failed to reveal the
      KGF transcript in several cultured human pancreatic cancer cell lines. However,
      by PCR analysis, some of the cell lines expressed KGF mRNA. Furthermore, 5 of 7
      tested cell lines expressed the KGF receptor, and the growth of one cell line was
      enhanced by human recombinant KGF. These results suggest that KGF may participate
      in aberrant paracrine and autocrine pathways in human pancreatic cancer.

PMID- 7575608
TI  - Thermodynamic characterization of the interaction between cytochrome b5 and
      cytochrome c.
AB  - In recent years many studies have been directed toward the elucidation of the
      interaction mechanisms within protein-protein complexes. One of the best studies
      protein-protein complexes has been the cytochrome b5 and cytochrome c electron
      transfer pair. Thermodynamic information about the association process has been
      obtained through methods which indirectly measure the binding between the
      proteins. We report here the use of Isothermal Titration Calorimetry to
      characterize the association of Rat cytochrome b5 and Horse cytochrome c. The
      association is accompanied by an unfavorable enthalpy change (+1.0 +/-0.1
      Kcal/mole) and a large stabilizing change in entropy (33.9 +/-0.6 eu).

PMID- 7575609
TI  - Rab4, but not the transferrin receptor, is colocalized with GLUT4 in an insulin
      sensitive intracellular compartment in rat skeletal muscle.
AB  - The role of Rab4, a small molecular weight GTP binding protein implicated in
      endosomal/plasma membrane (PM) recycling, in the translocation of the GLUT4
      transporter in rat skeletal muscle was studied. Muscle membranes, prepared by
      subcellular fractionation of control and insulin treated rat skeletal muscle,
      were subjected to SDS/PAGE and immunoblot analyses. Insulin treatment caused an
      increase in GLUT4 in a plasma membrane (PM) enriched fraction from an
      intracellular membrane (IM) fraction. Immunoprecipitation of GLUT4 vesicles from
      the IM compartment revealed that Rab4 could be coprecipitated. Importantly,
      however, and unlike in adipocytes, immunoisolated GLUT4 vesicles from rat
      skeletal muscle contained no detectable immunoreactivity towards the transferrin
      receptor, suggesting that Rab4 was present in a GLUT4 IM pool that was not
      characteristic of early endosomes. The involvement of Rab4 in GLUT4 translocation
      was further supported by the finding that insulin treatment resulted in a
      significant (43%) reduction in Rab4 in the IM compartment. Our results suggest
      (i) that insulin induces the loss of both GLUT4 and Rab4 from the same IM
      compartment, (ii) that Rab4 may be involved in GLUT4 translocation based on its
      coprecipitation with the transporter from the insulin-sensitive pool and (iii)
      that Rab4 can be localized to intracellular membranes which appear not to be of
      early endosome origin.

PMID- 7575610
TI  - Negative and positive elements in the promoter region of the human apoferritin L
      gene.
AB  - We have characterized the promoter of the human gene coding for the apoferritin L
      subunit. Transient transfections of 5' and 3' deletion mutants indicate that the
      efficiency of the L promoter depends on both negative and positive cis-elements,
      located upstream and downstream of the transcription start point. DNaseI
      footprinting analysis of this DNA region revealed the presence of five protected
      segments. The most upstream one (element 1) corresponds to the negative cis
      element and is recognized by factor(s) sharing a GC-sequence specificity. Three
      positive elements are in the region upstream of the start of transcription; a
      fifth positive cis-element (element 5) is localized in the first exon of the L
      gene.

PMID- 7575611
TI  - Antagonism of COUP-TF and PPAR alpha/RXR alpha on the activation of the malic
      enzyme gene promoter: modulation by 9-cis RA.
AB  - We previously demonstrated that heterodimers of the Peroxisome Proliferator
      Activated Receptor alpha (PPAR alpha) and the Retinoid X Receptor alpha (RXR
      alpha) stimulate malic enzyme gene transcription through a regulatory element in
      the promoter region (ME-PPRE). In this report, we show that the orphan nuclear
      receptor COUP-TF also displays affinity for the ME-PPRE and competes with PPAR
      alpha/RXR alpha for binding to this element. In transient transfections of a
      reporter driven by the MRE-PPRE in a heterologous or in the homologous promoter
      context, COUP-TF strongly antagonizes the transactivation by PPAR alpha RXR alpha
      in the absence of exogenously added ligands. Although 9-cis RA did not further
      enhance the transcriptional effects of the heterodimers activated by
      ciprofibrate, it greatly impaired the suppressive effects of COUP-TF on the
      ciprofibrate activated PPAR alpha/RXR alpha. We conclude that the antagonism by
      COUP-TF uncovers differential activation states of PPAR alpha/RXR alpha
      heterodimers in the absence and in the presence of 9-cis RA.

PMID- 7575612
TI  - Activation of 2-aminofluorene by prostaglandin endoperoxide H synthase-2.
AB  - Prostaglandin endoperoxide H synthase is the key enzyme in the conversion of
      arachidonic acid to tissue prostanoids. Two isoforms of prostaglandin
      endoperoxide H synthase have been identified: PHS-1 is constitutively expressed
      in most tissues under normal physiological conditions and PHS-2 is expressed in
      response to inflammatory agents, tumor promotors, and other agents related to
      mitogenesis. Previous work demonstrated that PHS-1 can activate arylamine
      carcinogens. We report here that PHS-2 can also activate an arylamine carcinogen
      to form DNA adducts. This is shown by: (1) use of purified ovine PHS-2 to form
      DNA adducts; (2) increased DNA adduct formation, PHS-2 mRNA, and PHS-2 protein
      after treatment of HUVEC cells with the PHS-2 inducer PMA; and (3) transient
      expression of PHS-2 cDNA in COS-1 cells gave rise to both elevations of PHS-2
      enzyme protein and DNA adduct formation. Finally, two PHS inhibitors, aspirin and
      indomethacin, showed significant inhibition of PHS-2-mediated DNA adduct
      formation.

PMID- 7575613
TI  - Evidence that pH-titratable groups control the activity of a large epithelial
      chloride channel.
AB  - The effects of pH changes were examined on the properties of a large, voltage
      dependent, epithelial Cl- channel from bovine tracheal cells. Alkaline solutions
      in the range pH = 7.4-9.2 had no detectable effects on channel conductance or
      gating. However, acid solutions significantly reduced channel open probability,
      raising the voltage required to open the channel. Analysis of channel activity in
      the acidic pH range suggested that at least one charged group on the channel with
      an apparent pK = 6.09, is responsible for its voltage dependence. Neutralization
      of this charge does not eliminate the voltage dependence, but changes the energy
      difference between the closed and open states. The absence of any change in
      channel conductance over this wide pH range suggests that the protonation site is
      far removed from the channel permeation pathway.

PMID- 7575614
TI  - Apo-dystrophins (Dp140 and Dp71) and dystrophin splicing isoforms in developing
      brain.
AB  - PCR studies have shown that exons 71-74 are spliced out in most dystrophin mRNA
      transcripts in the brain. We have prepared new monoclonal antibodies against the
      syntrophin-binding region of dystrophin encoded by exons 73-74 and examined three
      protein products of the dystrophin gene in brain; the widely distributed Dp71,
      the recently discovered, brain-specific Dp140 and dystrophin itself. Exon 73-74
      mAbs bound to all three proteins in brain and the extent of binding suggests that
      alternatively spliced dystrophins are less prominent at the protein level than
      predicted by PCR data. Dp140, unlike Dp71, was found to be present at much higher
      levels in foetal brain than in adult brain. If lack of functional Dp140 is the
      cause of the cognitive impairment in some Duchenne muscular dystrophy patients,
      this result suggests that the effects may occur early in development, which would
      reduce the options for therapeutic intervention.

PMID- 7575615
TI  - Progressive hyperphosphorylation of neurofilament heavy subunits with aging:
      possible involvement in the mechanism of neurofilament accumulation.
AB  - Abnormal accumulations of phosphorylated neurofilaments occur both in normal
      senescence and in age-associated neurodegenerative diseases. In the present work,
      we study the physicochemical properties of neurofilaments isolated from rats of
      controlled ages. Aging induces in vivo hyperphosphorylation of the heavy
      neurofilament subunit without affecting in vitro neurofilament phosphorylation by
      the neurofilament-associated protein kinase. Interactions in vitro between
      neurofilaments from very old rats occur at higher rate and extent than that of
      neurofilaments from younger animals. These results support the hypothesis that
      the abnormal accumulation of neurofilaments observed in nervous tissues from
      aging mammals results from an altered equilibrium in situ between interconnected
      and independent neurofilaments.

PMID- 7575617
TI  - Transforming growth factor-beta inhibits the cytokine-mediated expression of the
      inducible nitric oxide synthase mRNA in human retinal pigment epithelial cells.
AB  - Human retinal pigment epithelial (RPE) cells in culture respond to a mixture of
      cytokines (IFN-gamma, IL-1 beta, TNF-alpha) by producing large amounts of nitric
      oxide. Transforming growth factor-beta, unlike other growth factors, was found to
      inhibit this response by more than 75%. The expression of mRNA for the inducible
      form of nitric oxide synthase in RPE cells treated with cytokines was
      demonstrated by reverse transcription-polymerase chain reaction, sequencing of
      the PCR product and northern blotting. Transforming growth factor-beta was highly
      effective in inhibiting (by 75%) the cytokine-induced nitric oxide synthase mRNA
      expression. This response by RPE may play an important role in the etiology of
      infectious and inflammatory diseases affecting retina.

PMID- 7575616
TI  - Interleukin-1 and oncostatin M in combination promote the release of collagen
      fragments from bovine nasal cartilage in culture.
AB  - Interleukin-1 (IL-1) and Oncostatin M (OM) induce a rapid and reproducible
      release of proteoglycan and collagen fragments from bovine nasal cartilage in
      culture. Over 90% of the total collagen was released by day 14 compared to a
      variable release with IL-1 alone. This release was accompanied by the appearance
      of collagenolytic activity in the medium that cleaved collagen specifically at
      the one quarter/three quarter position. Tissue inhibitor of metalloproteinases
      (TIMP-1) activity was low or absent in media from resorbing tissue. The breakdown
      of cartilage collagen could be prevented by the addition of BB94, a specific
      matrix metalloproteinase (MMP) inhibitor. These results suggest that T
      cell/macrophage products within inflammed joints can interact with pro
      inflammatory cytokines and lead to the rapid destruction of connective tissue
      collagen.

PMID- 7575618
TI  - Transcriptional regulation of the apolipoprotein B-100 gene: identification of
      cis-acting elements in the first nontranslated exon of the human apolipoprotein B
      100 gene.
AB  - Apolipoprotein B-100, produced primarily in the human liver, is the sole protein
      component of low-density lipoprotein and serves as a ligand for the LDL receptor.
      Two cis-acting positive elements between -128 and -70 control hepatic cell
      specific expression of the human apoB gene (H. K. Das, T. Leff, and J. L.
      Breslow, J. Biol. Chem. 263: 11452-11458, 1988). In this study, two apoB cis
      acting elements (+20 to +40; +43 to +53) have been identified using DNase I
      footprint analysis. Through in vitro mutagenesis and transient transfection
      experiments in Hep G2 and HeLa cells, the element (+20 to +40) was observed to
      have a negative effect on transcription of the apoB gene. The element (+43 to
      +53) was found to have a strong positive effect on apoB gene transcription in Hep
      G2 cells and mild positive effect in HeLa cells. Therefore these two cis-acting
      elements mediate hepatic-cell specific expression of the apolipoprotein gene by
      interacting with trans-acting protein factors.

PMID- 7575619
TI  - Identification of cellular protein that can interact specifically with the basic
      helix-loop-helix domain of the aromatic hydrocarbon receptor.
AB  - The Ah receptor is a basic helix-loop-helix (bHLH)-PAS protein and functions as a
      ligand-activated DNA binding protein directly interacting with target genes by
      binding to xenobiotic responsive elements. We have sought to identify possible
      cellular proteins that can interact with the Ah receptor. The bHLH domain of the
      Ah receptor was fused to glutathione-S-transferase (GST), and the resulting
      fusion protein was used as a probe to help us to identify receptor associated
      protein(s). At least one such protein, 45kDa (p45), was detected in mouse liver
      extracts, but it does not bind to the bHLH domain of the Ah receptor nuclear
      translocator, nor to the transactivation domain of Ah receptor or GST alone.

PMID- 7575620
TI  - OK-1035, a selective inhibitor of DNA-dependent protein kinase.
AB  - Screening for inhibitors of DNA-dependent protein kinase (DNA-PK) revealed 3
      cyano-5-(4-pyridyl)-6-hydrazonomethyl-2-pyridone, designated OK-1035, to be a
      potent and selective inhibitor. When a synthetic peptide was used as a substrate,
      OK-1035 caused 50% inhibition of DNA-PK activity at 8 microM, a concentration
      more than 50 times lower than those required against seven other protein kinases
      tested. OK-1035 inhibited the phosphorylation by DNA-PK of consensus peptide as
      well as that of recombinant human wild type-p53. Kinetic studies indicated that
      OK-1035 inhibited DNA-PK activity in an ATP-competitive manner.

PMID- 7575621
TI  - Preferential expression of osteocalcin-related protein mRNA in gonadal tissues of
      male mice.
AB  - It was recently reported that the mouse genome contains an osteocalcin cluster
      formed by three genes, OG1, OG2 and ORG, in order from the 5' to the 3' end of
      the cluster. These three genes exhibit close structural homology. OG1 and OG2 are
      abundant in bone, but ORG is expressed in nonosteoid tissues, especially in
      kidney and lung. Previous studies using transgenic mice carrying diphtheria toxin
      A-chain gene linked to the rat osteocalcin (OG2) promoter have revealed that the
      OG2 promoter is active not only in osteoblasts, but also in testis. In this
      study, reverse transcription-polymerase chain reaction was used to study the
      expression of these three genes in mouse tissues (including testis). Here we
      report for the first time that mouse ORG is extensively transcribed in male
      gonadal tissues including seminal vesicle, preputial gland, testis, caput
      epididymis and cauda epididymis. These findings suggest that ORG may play a role
      in differentiation and/or maintenance of male gonadal tissues.

PMID- 7575622
TI  - Cloning, subcellular localization and expression of CHL1, a subunit of magnesium
      chelatase in soybean.
AB  - Mg-insertion is the first committed step in chlorophyll synthesis and is
      catalyzed by Mg-chelatase. In photosynthetic bacteria, bchI gene product was
      suggested to be a subunit of Mg-chelatase. We isolated a bchI homolog from a
      soybean cDNA library and designated it as chlI. CHLI consisted of 421 amino acid
      residues and the sequence exhibited a high similarity to other BchI homologs.
      CHLI contained an ATP-binding motif found in other BchI homologs. CHLI was
      localized in the soluble fraction in soybean chloroplasts, suggesting that it was
      a stromal subunit of Mg-chelatase. chlI mRNA in cell culture (SB-P) of soybean
      was reversibly induced by light.

PMID- 7575623
TI  - Molecular cloning, tissue expression of human xanthine dehydrogenase.

PMID- 7575624
TI  - Molecular cloning of a new erythropoiesis-stimulating activity (ESA36) from
      Streptomyces thermoviolaceus and expression in Escherichia coli.
AB  - Previous studies have shown that an Actinomycetes strain produces a novel protein
      with a molecular weight of 87,000 which stimulated the growth of murine erythroid
      progenitors in vitro, and we purified the protein. In this study, we have
      isolated and sequenced a clone encoding a polypeptide which had the equivalent
      activity. The clone contained an open reading frame of 334 amino acids. The
      activity was confirmed by the expression in E. coli as a fusion protein with
      glutathion S-transferase (GST). Based on the differences of molecular weight and
      N-terminal amino acid sequences, this protein was considered to be different from
      that previously reported and was named "ESA36".

PMID- 7575625
TI  - Butyrate and TGF-beta downregulate Na,K-ATPase expression in cultured proximal
      tubule cells.
AB  - Attempts were made to examine the effect of growth inhibitors on regulation of
      Na,K-ATPase in primary cultures of renal proximal tubule cells. We observed that
      both TGF-beta and butyrate induced dose dependent decrease of Na,K-ATPase
      activity. The time course studies showed that the effect of TGF-beta preceded the
      effect of butyrate on inhibition of Na,K-ATPase activity. Both butyrate- and TGF
      beta-induced inhibition of this enzyme were in general mediated by
      transcriptional decreases of alpha and beta mRNA and therefore also protein
      abundance. Like its effect on Na,K-ATPase activity, TGF-beta compared to butyrate
      induced much earlier decline in Na,K-ATPase alpha and beta mRNA and protein
      abundance. Butyrate did not affect gene expression of TGF-beta and anti-TGF-beta
      antibody had no effect on butyrate-induced inhibition of DNA synthesis.
      Obviously, both butyrate and TGF-beta can inhibit the expression of Na,K-ATPase
      alpha and beta mRNA, but TGF-beta does not mediate butyrate's effect.

PMID- 7575626
TI  - The influence of dystrophin on lateral diffusion of proteins in sarcolemma of L
      185 and C2 myoblasts and mature striated muscle cells of rats and mice, as
      measured by FRAP technique.
AB  - The expression of dystrophin can be suppressed in cultured skeletal muscle cells
      (coded L-185 from rat, and C2 from mouse) after a proper genetic manipulation.
      The influence of presence or absence of dystrophin on the lateral diffusion
      constant of Con-A-receptors was studied in the cell membrane of such cells (and
      also of mature skeletal muscle fibres of rat and mouse) by means of the
      fluorescence recovery after photobleaching (FRAP) technique, applying a novel
      fluorescent label called Con-A-BODIPY-FI conjugate. It has been established that
      the normal maturation, of myoblasts into skeletal muscle fibres involves a
      significant decrease of the mobility of Con-A receptors in the sarcolemma. In the
      absence of dystrophin, this maturation process cannot take place; the membrane
      proteins display an increasing mobility during the culture time, which is of
      lethal effect for these cells.

PMID- 7575628
TI  - Selective inhibition of phosphatidylinositol 3-kinase by phosphatidic acid and
      related lipids.
AB  - Activation of phosphatidylinositol 3-kinase (PI 3-kinase) is necessary for
      stimulation of cell division and inhibition of apoptosis in several cell types.
      We report that a synthetic phosphonolipid, 4-(hexadecyloxy)-3-(S)-methoxybutyl
      phosphonic acid (PoA), as well as the naturally occurring lipids, phosphatidic
      acid and lyso-phosphatidic acid, are potent and specific inhibitors of PI 3
      kinase. The IC50's for inhibition using phosphatidylinositol as substrate ranged
      from 10-20 microM. PoA is also the putative primary intracellular metabolite
      following phospholipase D hydrolysis of the anti-tumour ether lipid, 2'
      (trimethylammonio) ethyl-4-(hexadecyloxy)-3-(S)-methoxybutanephosphonate. These
      results suggests that inhibition of PI 3-kinase following metabolic degradation
      of ether lipids by phospholipase D may contribute to the cytotoxicity of these
      compounds. The sensitivity of PI 3-kinase to PA and lyso-PA could imply cross
      talk between the phospholipase D and PI 3-kinase signal transduction pathways in
      vivo.

PMID- 7575627
TI  - Ca(++)-calmodulin-dependent phosphorylation and dephosphorylation of rat parotid
      secretion granules.
AB  - In our studies on the control of fusion of secretion granules with the plasma
      membrane which occurs during exocytosis, we have recently found that Ca++ and
      calmodulin stimulated the fusion of isolated parotid secretion granules with
      isolated inside-out plasma membrane vesicles. We are now examining the
      possibility that they do so by stimulating protein phosphorylation. Secretion
      granules were isolated from rat parotid by differential and gradient
      centrifugation and incubated with [Y32P]ATP. The granules were solubilized with
      sodium dodecylsulfate and the proteins resolved on a 7-15% polyacrylamide gel.
      Calmodulin plus Ca++, but neither alone, stimulated phosphorylation of four
      proteins with molecular masses of 64, 58, 55 and 31 kDa, and decreased the
      phosphorylation of a 36 kDa protein. Trifluoperazine and calmidazolium inhibited
      these effects. The results suggest that Ca++ and calmodulin may facilitate fusion
      of secretion granules with the plasma membrane by changing the phosphorylation
      state of one or more secretion granule proteins.

PMID- 7575629
TI  - Aggregation and concentration-dependent sorting of exocrine regulated secretory
      proteins.
AB  - Sorting between the regulated and the constitutive secretory pathway in exocrine
      cells is thought to involve aggregation of regulated secretory proteins. This
      study demonstrates that, unlike endocrine secretory proteins, exocrine secretory
      proteins, including amylase, do not undergo homotypic aggregation under the
      conditions found in the sorting organelles. Also, unlike other exocrine proteins,
      amylase does not aggregate with chondroitin sulfate. Since amylase exhibits
      heterotypic aggregation, the role of protein concentration in amylase sorting was
      tested in AR42J cells. Secretion was stimulated with substance P and
      cholecystokinin from both untreated and dexamethasone-treated cells, with more
      efficient stimulation from dexamethasone-treated cells. These results indicate
      that amylase sorting is enhanced when its expression is stimulated by
      dexamethasone treatment.

PMID- 7575631
TI  - Relationship between susceptibility to apoptosis and Fas expression in peripheral
      blood T cells from uremic patients: a possible mechanism for lymphopenia in
      chronic renal failure.
AB  - Chronic renal failure (CRF) is often complicated by lymphopenia, which may be
      partly responsible for immune deficiency. We hypothesized that lymphopenia in CRF
      might result from apoptosis of T cells in vivo. To elucidate the involvement of
      Fas antigen which mediates apoptosis, we analyzed Fas expression on peripheral
      blood T cells in uremic non-dialyzed (non-HD) patients and hemodialysis (HD)
      patients. T cells from both uremic groups expressed Fas with higher intensity
      than control T cells. When two uremic groups were compared, Fas intensity on T
      cells was significantly higher in non-HD patients than in patients on HD.
      Moreover, uremic T cells were shown to undergo accelerated apoptosis when
      cultured in vitro, in correlation with Fas expression. Our results suggest that T
      cells in CRF may undergo apoptosis by the Fas system and that hemodialysis
      treatment has beneficial effects in the light of the inhibition of T cell
      apoptosis.

PMID- 7575630
TI  - 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in
      brain.
AB  - The effects of anadamide, 2-arachidonoylglycerol and related compounds on the
      specific binding of a radiolabeled cannabinoid receptor ligand,[3H]CP55940, to
      synaptosomal membranes were examined. Anandamide, an endogenous cannabinoid
      receptor ligand, reduced the specific binding of [3H]CP55940 to synaptosomal
      membranes in a dose-dependent manner: the Ki value was 89 nM. 2
      Arachidonoylglycerol was also shown to bind appreciably to the cannabinoid
      receptor in competitive inhibition experiments. The apparent binding affinity was
      markedly increased when the binding assay was carried out in the presence of the
      esterase inhibitor DFP or at 0 degrees C. Free arachidonic acid and N
      palmitoylethanolamine were almost inactive in terms of binding to the cannabinoid
      receptor in synaptosomal membranes. 2-Arachidonoylglycerol may be an endogenous
      cannabinoid receptor ligand in the brain.

PMID- 7575632
TI  - Redox signalling by transcription factors NF-kappa B and AP-1 in lymphocytes.

PMID- 7575633
TI  - Differential antiviral activity of derivatized dextrans.
AB  - The antiviral activity of water-soluble dextrans derivatized with varying
      percentages of carboxymethyl, benzylamide, and sulfonate groups was evaluated.
      Several of the polymers exhibited potent antiviral activity against a variety of
      enveloped viruses, but not against non-enveloped viruses, and only when present
      during virus adsorption. The mechanism of activity against retroviruses [i.e.
      human immunodeficiency virus (HIV)] and herpes viruses (i.e. human
      cytomegalovirus) could be ascribed to inhibition of virus binding to the cells.
      An absolute requirement for anti-HSV activity appeared to be a sufficiently high
      percentage of benzylamide and benzylamide sulfonate groups. This did not,
      however, apply for human cytomegalovirus, respiratory syncytial virus, and HIV.
      The sensitivity of the latter viruses appeared to be influenced by factors other
      than the global chemical composition, which leads us to assume that physical
      factors such as the distribution and sequence of the substituents on the sugar
      backbone play an important role in the antiviral activity of the derivatized
      dextrans.

PMID- 7575634
TI  - Evidence for the activation of the signal-responsive phospholipase A2 by
      exogenous hydrogen peroxide.
AB  - The intracellular events that lead to arachidonic acid release from bovine
      endothelial cells in culture treated with hydrogen peroxide were characterized.
      The hydrogen peroxide-stimulated release of arachidonic acid was time- and dose
      dependent, with maximal release achieved at 15 minutes after the addition of 100
      microM hydrogen peroxide. Hydrogen peroxide-stimulated release of arachidonic
      acid was blocked with the phospholipase A2 inhibitor quinacrine. Treatment of the
      cells with hydrogen peroxide did not result in liberation of oleic acid,
      indicating that hydrogen peroxide exercised its effect on an arachidonate
      specific phospholipase. Pretreatment of the cells with antioxidants, transition
      metal chelators, and hydroxyl radical scavengers did not affect the hydrogen
      peroxide-stimulated arachidonic acid release, indicating that the response to
      hydrogen peroxide is not oxygen radical-mediated. The response to hydrogen
      peroxide does not appear to be calcium-dependent, due to the following two
      observations: (a) No increase in intracellular calcium was seen upon exposure of
      the FURA2-loaded cells to hydrogen peroxide at concentrations sufficient to
      release arachidonic acid, and (b) no change in the release response was detected
      in cells loaded with the intracellular calcium chelator BAPTA. Significant
      inhibition of arachidonic acid release was seen when the cells were pretreated
      with inhibitors of protein kinase C, but not with inhibitors of tyrosine kinase.
      The results of these studies indicate that hydrogen peroxide-stimulated
      arachidonic acid release is mediated by a specific signal-responsive
      phospholipase A2, and that this process is not mediated via the actions of either
      lipid peroxidation or calcium but, rather, that a stimulation of intracellular
      kinase activity is necessary for this response.

PMID- 7575635
TI  - Activation of NO:cGMP pathway by acetylcholine in bovine chromaffin cells.
      Possible role of Ca2+ in the down-regulation of cGMP signaling.
AB  - The production of cyclic GMP (cGMP) induced by acetylcholine and other stimuli
      was studied in bovine chromaffin cells. Acetylcholine increased intracellular
      cGMP in a transitory (peak at 2 min) and concentration-dependent manner
      (estimated half maximal increase, EC50 = 61 +/- 5 microM). NG-nitro-L-arginine
      methyl ester (NAME) inhibited such a rise in cGMP with a half maximal inhibitory
      concentration (IC50) of 231 +/- 55 microM. The acetylcholine-induced increase in
      cGMP was also inhibited by a calmodulin antagonist (calmidazolium, 30 microM) and
      by the absence of extracellular calcium. Other agents that strongly increased
      cytosolic calcium concentration ([Ca2+]i) as acetylcholine did, such as the
      nicotinic-agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP), high-KCl (50 mM),
      and ionomycin, also caused a rise in cGMP in cultured bovine chromaffin cells.
      Veratridine, an activator of sodium channels, produced a slowly developing
      calcium increase and no significant cGMP production. The muscarinic-agonist,
      muscarine, failed to increase cytosolic calcium, and was the weakest stimulator
      of cGMP production. cGMP formation, induced by sodium nitroprusside (SNP, 100
      microM) and by C-type natriuretic peptide (CNP, 100 nM), was inhibited by 30-40%
      by increasing [Ca2+]i with ionomycin. This inhibition was abolished by
      calmidazolium (30 microM) and by the absence of calcium in the extracellular
      medium. In conclusion, bovine chromaffin cells synthesize nitric oxide (NO) to
      activate guanylate cyclase in response to several stimuli, which increase
      [Ca2+]i. Moreover, the increase in [Ca2+]i also stimulates a Ca2+/calmodulin
      phosphodiesterase, which could down-regulate the levels of cGMP in these cells.

PMID- 7575636
TI  - Tiamulin inhibits human CYP3A4 activity in an NIH/3T3 cell line stably expressing
      CYP3A4 cDNA.
AB  - Tiamulin is an antibiotic frequently used in veterinary medicine. The drug has
      been shown to produce clinically important interactions with other compounds that
      are administered simultaneously. An NIH/3T3 cell line, stably expressing human
      cytochrome P450 (EC 1.14.14.1) cDNA (CYP3A4), was used to study the effect of
      tiamulin on CYP3A4 activity. The 6 beta-hydroxylation activity of testosterone,
      which is increased in CYP3A4-expressing cells compared to vector-transfected
      cells, showed reduced activity after incubation with 1 microM tiamulin and was
      completely reduced to background level after incubation with 2, 5 and 10 microM
      tiamulin. The CYP3A4-expressing cell line was used in combination with a shuttle
      vector containing the bacterial lacZ' gene to study the effect of tiamulin on
      CYP3A4-mediated mutagenicity of aflatoxin B1. The mutation frequency of aflatoxin
      B1 could be completely inhibited by tiamulin in CYP3A4-expressing cells, but no
      effect was observed on the mutation frequency of the direct mutagen
      ethylmethanesulphonate. Western blotting of homogenates of the CYP3A4-expressing
      cell line showed stabilization of CYP3A4 protein after incubation with tiamulin,
      supporting the hypothesis that the mechanism of inhibition is by binding of
      tiamulin to the cytochrome.

PMID- 7575637
TI  - Metformin induces an agonist-specific increase in albumin production by primary
      cultured rat hepatocytes.
AB  - Metformin (MET) is known to increase several biological effects of insulin (INS),
      but there is no information concerning its direct effects on protein synthesis.
      We studied the action of MET on albumin production by primary cultures of freshly
      isolated rat hepatocytes, alone or in combination with various agonists: INS, IGF
      1, EGF, thyroxin, and dexamethasone. While having no effect alone, MET in vitro
      potentiates the effects of INS, IGF-1, and EGF. When this increasing effect
      toward INS was studied over a broad concentration range, MET appeared to improve
      low-acting INS levels and to intensify the maximal INS effects. In contrast, MET
      did not change the production of albumin stimulated by thyroxin or dexamethasone.
      Animals chronically pretreated with MET in vivo showed a higher yield of isolated
      hepatocytes, better attachment, and especially higher viability after liver
      perfusion and during cell culture. This may largely explain why basal albumin
      rates were higher than in in vitro-treated cells. The effect of MET in the
      presence of the agonists exhibited the same agonist-specificity as in vitro. Our
      data provide new insights into the pharmacology of MET by showing that hepatic
      protein synthesis is increased by MET and INS. From the specificity of action of
      MET towards INS, IGF-1, and EGF (but not thyroxin or dexamethasone), we
      hypothesize that this biguanide may act on intracellular pathways located between
      membrane receptors and sites of branching in the signaling cascades shared by
      these agonists.

PMID- 7575639
TI  - Inhibition of 2,3-oxidosqualene cyclase and sterol biosynthesis by 10- and 19
      azasqualene derivatives.
AB  - The inhibition of 2,3-oxidosqualene-lanosterol cyclase (EC 5.4.99.7) (OSC) by new
      azasqualene derivatives, mimicking the proC-8 and proC-20 carbocationic high
      energy intermediates of the cyclization of 2,3-oxidosqualene to lanosterol, was
      studied using pig liver microsomes, partially purified preparations of OSC, and
      yeast microsomes. The azasqualene derivatives tested were: 6E- and 6Z-10aza-10,11
      dihydrosqualene-2,3-epoxide 17 and 18, 19-aza-18,19,22,23-tetrahydrosqualene-2,3
      epoxide 19 and its corresponding N-oxide 20, and 19-aza-18,19,22,23
      tetrahydrosqualene 21. The compounds 17 and 19 (i.e. the derivatives bearing the
      2,3-epoxide ring and the same geometrical configuration as the OSC substrate)
      were effective inhibitors, as shown by the Ki obtained using partially purified
      OSC: 2.67 microM and 2.14 microM, respectively. Compound 18, having an incorrect
      configuration and the 19-aza derivative 21, lacking the 2,3-epoxide ring, were
      poor inhibitors, with IC50 of 44 microM and 70 microM, respectively. Compound 21
      was a competitive inhibitor of OSC, whereas 17 and 19 were noncompetitive
      inhibitors, and showed a biphasic time-dependent inactivation of OSC, their
      apparent binding constants being 250 microM and 213 microM, respectively. The
      inhibition of sterol biosynthesis was studied using human hepatoma HepG2 cells.
      The incorporation of [14C] acetate in the C27 sterols was reduced by 50% by 0.55
      microM 17, 0.22 microM 19, and 0.45 microM 21, whereas 2 microM 18 did not affect
      sterol biosynthesis. In the presence of 17, 19 and 21, only the intermediate
      metabolites 2,3-oxidosqualene and 2,3,22,23-dioxidosqualene accumulated,
      demonstrating a very specific inhibition of OSC.

PMID- 7575638
TI  - Induction of cytochrome P-4502B1-related mouse cytochrome P-450 and regulation of
      its expression by epidermal growth factor/transforming growth factor alpha in
      primary hepatocyte culture.
AB  - Phenobarbital-dependent induction of mouse cytochrome P-450 (Cyp) orthologous to
      rat CYP2B1 and its modulation by hepatotrophic growth factors were examined in
      primary hepatocyte cultures. Compared to rat hepatocytes, induction in mouse
      hepatocytes was more rapid and effective. Ligands of the EGF receptor, epidermal
      growth factor, and transforming growth factor alpha inhibited induction on the
      basis of protein expression and CYP2B-associated 7-pentoxyresorufin-O-depentylase
      activity. Furthermore, EGF led to repression of accumulation of corresponding
      mRNA under phenobarbital, an effect not blocked by inhibition of protein
      synthesis under cycloheximide. Ligands of the EGF receptor may contribute towards
      the decrease in hepatic CYP expression observed during (pre)neoplastic
      development and regeneration.

PMID- 7575640
TI  - Bioavailability of phylloquinone and menaquinones after oral and colorectal
      administration in vitamin K-deficient rats.
AB  - Rats were made vitamin K-deficient by feeding them a diet devoid of vitamin K and
      by rigorously preventing coprophagy. After one week, circulating prothrombin
      concentrations were between 5 and 10% of initial values, and various amounts of
      phylloquinone, menaquinone-4, and menaquinone-9 were given in a single dose
      either subcutaneously, orally, or colorectally. The relative 'vitamin K
      activities' of these compounds were assessed by comparing their ability to
      support prothrombin synthesis after subcutaneous injection. Intestinal and
      colonic absorption were deduced from the difference between subcutaneous and
      either oral or colorectal administration of the vitamers. It is concluded that
      the colonic absorption of all three forms of vitamin K is extremely poor,
      suggesting that physiological menaquinones in the colon do not contribute
      substantially to vitamin K status in rats. Furthermore, the stimulation of
      prothrombin synthesis by menaquinone-9 lasted much longer than that by the two
      other K-vitamers, resulting in a substantially higher 'vitamin K activity' of
      menaquinone-9.

PMID- 7575641
TI  - Studies on the antitumor effects of analogues of 5,8-dideazaisofolic acid and 5,8
      dideazaisoaminopterin.
AB  - Six new analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin were
      synthesized in an effort to obtain enhanced antitumor activity. The modifications
      included the replacement of the 2-amino group by hydrogen or methyl as well as
      the inclusion of a methyl substituent at position 9. Based upon activity against
      L1210 leukemia cells in culture, three of the new analogues together with one
      compound described previously were evaluated for cytotoxicity in vitro using
      three human tumor cell lines (Colo 320 DM, Hep G2 and HL-60). The most effective
      compound was 2-desamino-N9-methyl-5,8-dideazaisoaminopterin (2c) with the HL-60
      cells being the most sensitive to its cytotoxic effects. These analogues were
      evaluated in vitro as inhibitors of dihydrofolate reductase (DHFR) and
      thymidylate synthase (TS) from human as well as bacterial (Lactobacillus casei)
      sources. All four of the 4-amino analogues were most effective toward L. casei
      DHFR compared with human DHFR, with 2-desamino-2-methyl-5,8-dideazaisoaminopterin
      (2d) and its 9-methyl derivative (2e) having 818- and 430-fold greater
      selectivity (L. casei/human). Most of the compounds studied were found to be only
      modest inhibitors of human TS (I50 values = 1.5 to 20 microM) and were therefore
      at least 40-fold less inhibitory than 10-propargyl-5,8-dideazafolic acid.
      Nevertheless, reversal of cytotoxicity studies with thymidine, hypoxanthine and
      folinic acid using the HL-60 cell line suggested that TS is the primary target
      for these analogues.

PMID- 7575642
TI  - Effects of tenidap on superoxide-generating enzymes. Non-competitive inhibition
      of xanthine oxidase.
AB  - The anti-rheumatic drug tenidap has been shown previously to attenuate superoxide
      production by activated neutrophils. Given the importance of leukocyte as well as
      endothelial cell derived superoxide in mediating inflammatory responses, the
      effects of tenidap on mammalian enzymes capable of generating superoxide were
      determined. Tenidap had no effect on the generation of superoxide by NADPH
      oxidase reconstituted from fractionated neutrophil lysates. However, significant
      inhibition of superoxide production by mixtures of hypoxanthine and xanthine
      oxidase was observed in the presence of 3-30 micrograms/mL tenidap. The kientics
      of xanthine oxidase inhibition by tenidap were non-competitive; the Ki of tenidap
      for xanthine oxidase was 11 micrograms/mL (34 microM). No inhibition of xanthine
      oxidase was observed in the presence of other known inhibitors of cyclooxygenase.
      Inhibition of xanthine oxidase may be a heretofore unrecognized mechanism of the
      antirheumatic effects of tenidap.

PMID- 7575643
TI  - Removal of anti-human immunodeficiency virus 2',3'-dideoxynucleoside
      monophosphates from DNA by a novel human cytosolic 3'-->5' exonuclease.
AB  - A 3'-->5' exonuclease has been highly purified from the cytosol of human acute
      lymphoblastic leukemia H9 cells. The apparent molecular weight of this enzyme was
      approximately 50,000, as indicated by its sedimentation in glycerol gradients.
      The exonuclease did not copurify with DNA polymerase activity, required MgCl2 for
      its exonucleolytic activity, and was inhibited by KCl above 60 mM. The enzyme was
      active on single-stranded DNA, DNA duplexes and DNA/RNA duplexes, and it was
      efficient at removing 3'-terminal mispairs from DNA. The products of the
      exonucleolytic reaction were deoxynucleoside 5'-monophosphates. The behavior of
      the exonuclease was examined on DNA terminated at the 3' end with a variety of
      dideoxynucleosides that are potent against human immunodeficiency virus type 1.
      The exonuclease has a broad substrate specificity; however, the rate of the
      enzymatic reaction varied among the D dideoxynucleosides tested (ddAMP = ddCMP >
      d4TMP > AZTMP). Similarly, the enzyme was examined for its reactivity with DNA
      terminated by either the D or L enantiomers of ddC, SddC or FddC. The removal of
      analogs with the native D configuration was at least 6-fold more rapid than that
      of the L-compounds, and the type of structural modification had an impact on the
      rate at which the D enantiomers were removed (SddCMP > ddCMP > FddCMP). The
      monophosphate forms of AZT, D4T, L-FddC and L-ddC were potent inhibitors of the
      exonuclease at micromolar concentrations, while D-ddCMP partially inhibited the
      enzyme at millimolar concentrations. Based on its physical and enzymatic
      properties, this exonuclease represents a novel enzyme that may have an important
      role in determining the relative potencies of dideoxynucleosides against human
      immunodeficiency virus type 1.

PMID- 7575644
TI  - Virtual kinetics: using statistical experimental design for rapid analysis of
      enzyme inhibitor mechanisms.
AB  - Modern automated drug-screening can generate hundreds of inhibitor leads from
      diverse chemical sources in a short period of time. Traditional methods of
      inhibitor analysis are resource intensive and limit the number of inhibitors that
      can be analyzed for their mechanism of inhibition. This paper presents methods we
      have developed for rapid estimation of both potency and mechanism of potential
      inhibitor leads for a biochemically complex screening target (protein kinase C)
      using commercially available computer programs for statistical experimental
      design. Our findings indicate that, with careful choice of factor levels,
      statistical experimental design clearly identifies the various interactions of
      the assay components with inhibitors. Suitably plotted, the data can be used to
      examine the competitive nature of the inhibitor and can provide estimates of IC50
      and Michaelis constants useful for planning further kinetic work. The techniques
      used are amenable to automation and should be useful for identifying inhibitors
      that may have only marginal potency, but exhibit desirable mechanistic profiles
      suitable for structural analoging efforts.

PMID- 7575645
TI  - Potent inhibition of yeast-expressed CYP2D6 by dihydroquinidine, quinidine, and
      its metabolites.
AB  - The inhibitory effects of dihydroquinidine, quinidine and several quinidine
      metabolites on cytochrome P450 2D6 (CYP2D6) activity were examined. CYP2D6
      heterologously expressed in yeast cells O-demethylated dextromethorphan with a
      mean Km of 5.4 microM and a Vmax of 0.47 nmol/min/nmol. Quinidine and
      dihydroquinidine both potently inhibited CYP2D6 metabolic activity (mean Ki =
      0.027 and 0.013 microM, respectively) in yeast microsomes and in human liver
      microsomes. The metabolites, 3-hydroxyquinidine, O-desmethylquinidine and
      quinidine N-oxide also inhibited CYP2D6, but their Ki values (0.43 to 2.3 microM)
      were one to two orders of magnitude weaker than the values for quinidine and
      dihydroquinidine. There was a trend towards an inverse relationship between Ki
      and lipophilicity (r = -0.90, N = 5, P = 0.07), as determined by the retention
      time parameter k' using reverse-phase HPLC. Thus, although the metabolites of
      quinidine have the capacity to inhibit CYP2D6 activity, quinidine and the
      impurity dihydroquinidine are the important inhibitors of CYP2D6.

PMID- 7575646
TI  - Role of ascorbate in protection by nitecapone against cardiac ischemia
      reperfusion injury.
AB  - The antioxidant properties of nitecapone, a catechol derivative and an inhibitor
      of catechol-O-methyltransferase, were reported recently. In the present study,
      the influence of nitecapone on isolated rat heart ischemia-reperfusion injury was
      investigated to elucidate its cardioprotective role. Nitecapone, administered in
      the perfusion buffer from the beginning of the pre-ischemic phase, significantly
      improved recovery of cardiac mechanical function, suppressed enzyme leakage in
      the coronary effluent, and minimized loss of ascorbate, compared with the control
      group. In rats fed a diet containing 4% ascorbate, myocardial ascorbate content
      in ascorbate-fed rats after ischemia-reperfusion was higher than that in control
      rats fed a normal diet without ischemia. However, supplemented rats did not show
      any beneficial effects on cardiac mechanical recovery or enzyme leakage,
      suggesting that maintenance of tissue ascorbate level is not the cause, but the
      result of the protective effects of nitecapone against cardiac ischemia
      reperfusion injury. The iron-chelating effect of nitecapone was also tested. It
      was confirmed, using electron spin resonance, that 50 microM nitecapone chelates
      the same concentration of iron released from the heart into the coronary
      effluent. Hence, the iron-chelating ability of nitecapone may be responsible, at
      least in part, for its cardioprotective effects in ischemia-reperfusion injury.

PMID- 7575647
TI  - Elevated aromatic-L-amino acid decarboxylase in human carcinoid tumors.
AB  - The carcinoid neoplasm is marked by excessive serotonin, synthesized by the
      conversion of tryptophan (Trp) to 5-hydroxytryptophan by tryptophan hydroxylase
      (TPH) (EC 1.14.16.4) and decarboxylation of 5-hydroxytryptophan by aromatic-L
      amino acid decarboxylase (AAAD) (EC 4.1.1.28). Because almost no biochemical data
      were available on human carcinoid TPH and AAAD, we have characterized these
      enzymes as a preliminary step to developing mechanism-based agents selective
      against carcinoid tumors. TPH was detected in all fourteen carcinoids analyzed
      [Km = 185 +/- 17 microM (mean +/- SEM); Vmax = 2.4 +/- 1.2 nmol/hr/mg protein].
      AAAD was detected in thirteen tumors (Km = 45 +/- 6.7 microM; Vmax = 11 +/- 2.0
      nmol/min/mg protein). In a subset of hepatic metastatic tumors obtained with
      adjacent normal liver, the Km and Vmax of TPH (N = 6) and the Km of AAAD (N = 7)
      were comparable in both tissues. However, the Vmax of carcinoid AAAD was 50-fold
      higher (P < 0.002) than that in normal liver (13 +/- 3.1 vs 0.26 +/- 0.04
      nmol/min/mg protein). Western immunoblot analysis indicated that AAAD polypeptide
      content of carcinoid tumor was > 20-fold higher than in adjacent normal liver.
      These results suggest that AAAD might be an appropriate target for enzyme
      activated cytotoxic agents for carcinoid tumors.

PMID- 7575648
TI  - Evaluation of a series of N-alkyl benzomorphans in cell lines expressing
      transfected delta- and mu-opioid receptors.
AB  - Transfection of individual opioid receptors in Chinese hamster ovary (CHO) cells
      provides a pure, homogeneous population of receptors for screening drug
      candidates, and an alternative to the use of selective ligands. To evaluate the
      potential of this system, we chose a series of (-)-5,9 alpha-dimethyl-2-hydroxy-N
      substituted-6,7-benzomorphans, for which the receptor selectivity and in vivo
      activity had been characterized recently, and tested them in CHO cells stably
      transfected with either the rat delta-opioid receptor or the mouse mu-opioid
      receptor. [3H]Diprenorphine was used to measure opioid receptors in P2 membrane
      preparations. A Bmax of 7.58 +/- 0.8 pmol/mg protein and a Kd of 0.42 +/- 0.04 nM
      was obtained in the mu-opioid receptor expressing cell line used in these
      studies. In addition, [3H]naltrindole was used to confirm the delta-specificity
      of the cloned receptor. Both compounds gave a Bmax of 1.2 pmol/mg in the CHO
      cells expressing the rat delta-opioid receptor. Displacement assays were
      performed with eleven (-)-N-alkyl-benzomorphans in the absence and presence of
      150 mM NaCl, as well as known delta- and mu-selective agonists. Sodium reduced
      agonist affinity in the transfected cell lines. The benzomorphan compounds
      displayed a range of affinities in the mu- and delta-opioid receptor expressing
      cell lines. Good correlations were found between their affinities at the cloned
      mu- and delta-opioid receptors and those in rat brain and monkey cortex (r2 from
      0.73 to 0.89, P < 0.001). Comparative analysis of Ki values with in vivo potency
      in the mouse tail flick test indicated a high degree of correlation between
      antinociception and affinity in the mu-opioid receptor cell line (r2 = 0.83, p <
      0.0001). Lesser correlations were found between antinociception in the mouse and
      affinity at the rat mu-opioid receptor (r2 = 0.6610) and at the monkey mu-opioid
      receptor (r2 = 0.695). In sum, these studies indicate that the cell lines
      expressing the cloned mu- and delta-opioid receptors are appropriate models for
      determining the binding affinities of this class of opioid compounds. The
      diminishing correlations found between species when comparing in vitro and in
      vivo activity suggest that caution should be taken when extrapolating binding
      data to pharmacological activity among species.

PMID- 7575649
TI  - Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent
      leflunomide.
AB  - Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4-trifluoromethylphenyl)-4
      isoxazole carboximide] is an immunosuppressive agent effective in the treatment
      of rheumatoid arthritis. In spite of its clinical potential, its mechanism of
      action has not been elucidated. Recent studies suggest that leflunomide may
      interfere with the metabolism of pyrimidine nucleotides. In our studies, the
      active metabolite of leflunomide, RS-61980 (A77 1726, 2-hydroxyethylidene
      cyanoacetic acid-4-trifluoromethyl anilide), was cytostatic towards a human T
      lymphoblastoma cell line (A3.01). The inhibition of growth could be overcome
      completely by uridine. The other nucleosides, cytidine, adenosine and guanosine,
      did not overcome the effect of the compound. Since uridine is a precursor for the
      salvage synthesis of UMP, we propose that RS-61980 may be inhibiting the de novo
      pathway of UMP synthesis. Using human cells, the six enzymes catalyzing de novo
      UMP biosynthesis were tested for their sensitivity towards RS-61980. Only one of
      the enzymes, dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) was inhibited by RS
      61980 with a Ki value of 2.7 +/- 0.7 microM. The other five enzymes were not
      affected. The inhibition exhibited mixed-type kinetics towards both substrates,
      dihydroorotic acid and coenzyme Q. These results suggest that the molecular
      target of leflunomide action is DHODH. The immunomodulating activity may be
      related to the inhibition of UMP synthesis in proliferating lymphocytes.

PMID- 7575650
TI  - Inhibition of monoamine oxidase by isoquinoline derivatives. Qualitative and 3D
      quantitative structure-activity relationships.
AB  - A series of isoquinolines, N-methyl-1,2-dihydroisoquinolines, N-methyl-1,2,3,4
      tetrahydroisoquinolines, 1,2,3,4-tetrahydroisoquinolines, and N
      methylisoquinolinium ions were tested as inhibitors of monoamine oxidases A and
      B. All compounds were found to act as reversible and time-independent MAO
      inhibitors, often with a distinct selectivity towards MAO-A. As a class, the N
      methylisoquinolinium ions were found to be the most active MAO-A inhibitors, with
      N-methyl-6-methoxyisoquinolinium ion emerging as a potent (IC50 = 0.81 microM)
      and competitive MAO-A inhibitor. Comparative molecular field analysis (CoMFA, a
      3D-QSAR method) of MAO-A inhibition was performed using the data reported here
      and in the literature. Using the steric and lipophilic fields of the inhibitors,
      quantitative models with reasonable predictive power were obtained that point to
      the importance of steric, lipophilic, and polar interactions in modulating MAO-A
      inhibitory activity.

PMID- 7575651
TI  - The low-affinity dihydropyridine receptor and Na+/Ca2+ exchanger are associated
      in adrenal medullary mitochondria.
AB  - The effect of Ca2+ channel-acting drugs on bovine adrenal mitochondria Ca2+
      movements was investigated. Mitochondrial Ca2+ uptake is performed by an energy
      driven Ca2+ uniporter with a Km of 20.9 +/- 3.2 microM and Vmax of 148.1 +/- 7.2
      nmol 45Ca2+ min-1 mg-1. Ca2+ release is performed through an Na+/Ca2+ antiporter
      with a Km for Na+ of 4.2 +/- 0.5 mM, a Vmax of 7.5 +/- 0.4 nmol 45Ca2+ min-1 mg
      1, and a Hill coefficient of 1.4 +/- 0.2 Ca2+ efflux through the mitochondrial
      Na+/Ca2+ exchanger was inhibited by several dihydropyridines (nitrendipine,
      felodipine, nimodipine, (+)isradipine) and by the benzothiazepine diltiazem with
      similar potencies. In contrast, neither CGP 28392, Bay-K-8644, amlodipine, nor
      verapamil had any effect on Ca2+ efflux. Nitrendipine at 20 microM modified
      neither the Km nor the Hill coefficient for Na+, whereas the Vmax was reduced to
      2.9 nmol 45Ca2+ min-1 mg-1, thus demonstrating noncompetitive modulation of the
      Na+/Ca2+ exchanger. None of the Ca2+ channel-acting drugs assayed at 100 microM
      affected Ca2+ influx through the uniporter. Ca2+ channel blockers inhibited the
      Na+/Ca2+ antiporter and displaced the specific binding of [3H]nitrendipine to
      intact mitochondria with Ki values similar to the IC50s obtained for the
      inhibition of the Ca2+ efflux. Ca2+ channel-acting drugs that did not inhibit the
      Na+/Ca2+ exchanger (amlodipine, CGP 28392, Bay-K-9644, and verapamil, at
      concentrations of 100 microM or higher) had no effect on [3H]nitrendipine
      binding. These results suggest that the adrenomedullary mitochondrial
      dihydropyridine receptor is associated with the Na+/Ca2+ exchanger.

PMID- 7575653
TI  - Behavior of N-acylated daunorubicins in MDR1 gene transfected and parental cells.
AB  - The substrate specificity of the P-glycoprotein (P-170), a multidrug transporter,
      was studied using N-acylated daunorubicin derivatives and four MDR1 cDNA
      transfected cell lines. Results showed that N-acetyl-daunorubicin is a substrate,
      but the longer fatty acid derivatives, N-octanoyl and N-dodecanoyl daunorubicins,
      are not. This conclusion was reached by flow cytometric drug uptake assay, cell
      proliferation assays, and confocal microscopy. It was concluded that the longer
      fatty acid derivatives interact with plasma membranes in a way that affected P
      glycoprotein function.

PMID- 7575652
TI  - Effects of anandamide on hepatic fatty acid metabolism.
AB  - Incubation of rat hepatocytes with anandamide (arachidonoylethanolamide)
      inhibited acetyl-CoA carboxylase activity and fatty acid synthesis de novo
      without affecting fatty acid synthase. This was concomitant to a decrease in the
      intracellular levels of malonyl-CoA. Likewise, anandamide depressed both
      cholesterol synthesis de novo and the incorporation of exogenous palmitate into
      triacylglycerols and phospholipids. On the other hand, anandamide stimulated in
      parallel both carnitine palmitoyltransferase I activity and ketogenesis from
      palmitate, though ketogenesis from octanoate was unaffected. The effects of
      anandamide on hepatic fatty acid synthesis and oxidation were: (a) mimicked by
      arachidonic acid, a product of anandamide breakdown by anandamide amidase; (b)
      prevented by phenylmethylsulfonyl fluoride, an inhibitor of anandamide amidase;
      and (c) not affected by bisindolylmaleimide, a specific inhibitor of protein
      kinase C. Furthermore, delta 9-tetrahydrocannabinol had no effect on any of the
      parameters determined, ruling out the possibility that the effects of anandamide
      on hepatic fatty acid metabolism are mediated by the peripheral cannabinoid
      receptor. The results thus indicate that anandamide might function as a carrier
      of arachidonic acid in the modulation of hepatic fatty metabolism.

PMID- 7575654
TI  - Delayed effects of ciprofibrate on rat liver peroxisomal properties and proto
      oncogene expression.
AB  - Peroxisome proliferators (PPs) are non-genotoxic carcinogens in rodents. Their
      reversible effects on rat liver have been studied with ciprofibrate and
      fenofibrate. We found that with the hypolipemic drug fenofibrate a pause of 28
      days is sufficient for a return to normal status, whereas with the highly potent
      PP ciprofibrate, the stimulation of ACO mRNA levels remains after its withdrawal.
      We investigated the effects of the renewal of the treatment with PPs on other
      peroxisomal parameters and proto-oncogene expression using Wistar rats.
      Interestingly, c-myc expression was enhanced even upon drug withdrawal, and was
      more stimulated by the second exposure to ciprofibrate, while c-fos expression
      was unaltered. However, only slight differences in c-Ha-ras expression were
      observed. Therefore, the effects of PPs in the Wistar rats are not totally
      reversible within 28 days following withdrawal, depending on the drug used. These
      delayed effects of ciprofibrate could be a key to our understanding the
      hepatocarcinogenic effect of PPs in rodents.

PMID- 7575655
TI  - A cocaine-sensitive active dopamine transport in human lymphocytes.
AB  - Human lymphocytes possess a cocaine-sensitive high-affinity transport system for
      [3H]dopamine. [3H]Dopamine uptake was saturated with increasing dopamine
      concentrations and followed Michaelis-Menten kinetics. The uptake was
      temperature, sodium, and chloride dependent and was affected by the co-addition
      of ouabain, phloridzin, potassium cyanide, gramicidin, and other metabolic
      inhibitors. The uptake of dopamine was blocked significantly in a concentration
      dependent manner by cocaine and its congeners. Furthermore, preliminary evidence
      is presented linking the possible relationship between decreased lymphocyte
      [3H]dopamine uptake and chronic cocaine abuse in humans.

PMID- 7575656
TI  - Correlation between catalytic activity and protein content for the
      polymorphically expressed dihydropyrimidine dehydrogenase in human lymphocytes.
AB  - A TLC procedure was developed to determine dihydropyrimidine dehydrogenase (DPD)
      activity in human peripheral lymphocytes. The assay, which used radiolabeled
      uracil as a substrate, was validated using recombinant pig DPD in which it was
      demonstrated to yield kinetic constants similar to those found by methods that
      rely on either spectroscopic determination of NADPH oxidation or HPLC. DPD
      activity was measured in a group of human lymphocyte extracts, including an
      extract from a subject that actually presented toxicity to 5-fluorouracil
      treatment. Measurements of DPD protein content using western immunoblots revealed
      a significant correlation with activity levels in human lymphocytes. Thus, this
      correlation could be used to determine not only the levels of expression of this
      enzyme, which is the cause of an inherited genetic deficiency in pyrimidine
      catabolism, but also to estimate the degree of sensitivity to pyrimidine-based
      cancer drugs such as 5-fluorouracil.

PMID- 7575657
TI  - Inhibition of apoptosis by antioxidants in the human HL-60 leukemia cell line.
AB  - Cell death via apoptosis is an important event involved in a number of
      immunological processes. Recently, apoptosis has been associated with oxidative
      stress in a number of cell systems. Here we assessed the inhibitory capacity of
      different antioxidants on UV- and drug-induced apoptosis in the human leukemic
      cell line, HL-60. We found that the oxygen radical scavenger, BHA, the
      radioprotector cysteamine and the metal chelators, pyrrolidinedithiocarbamate
      (PDTC), diethyldithiocarbamate (DEDTC), and dimethyldithiocarbamate (DMDTC), were
      able to significantly inhibit nuclear fragmentation and reduce the formation of
      apoptotic bodies in UV-irradiated human leukemic cells. Both BHA and PDTC were
      found to reduce DNA fragmentation as assessed by in situ DNA nick-end labelling
      and quantification thereof using fluorescence flow cytometry. In addition to
      inhibiting UV-induced apoptosis, PDTC was also capable of reducing the amount of
      apoptosis induced by a range of cytotoxic drugs, such as actinomycin-D,
      camptothecin, etoposide, and melphalan, whereas BHA and cysteamine were not as
      effective in these cases after more than four hours in culture when compared to
      PDTC. To further elucidate the working mechanism of PDTC, we have looked at the
      effect of PDTC on DNA fragmentation in isolated nuclei, under conditions that
      promote activation of endogenous endonuclease involved in apoptosis. In contrast
      to ZnCl2, a potent inhibitor of endonuclease activity, PDTC was unable to inhibit
      DNA-ladder formation in this assay. Taken together, these results indicate that
      oxygen radicals may have a central role to play in the induction of apoptosis and
      that dithiocarbamates can serve as potent inhibitors of apoptosis induced by a
      wide variety of stimuli.

PMID- 7575659
TI  - Selective inhibition of neutrophil function by a peptide derived from lipocortin
      1 N-terminus.
AB  - A multi-faceted approach was used to investigate the effect of an anti
      inflammatory peptide derived from human lipocortin 1 N-terminus region (amino
      acid 2-26; termed human Ac2-26) on human neutrophil activation in vitro. When
      incubated with purified human neutrophils. human Ac2-26 produced a concentration
      dependent inhibition of elastase release stimulated by formyl-Met-Leu-Phe (fMLP),
      platelet-activating factor, or leukotriene B4, with an approximate EC50 of 33
      microM (100 micrograms/ml). At this concentration, human Ac2-26 also inhibited
      (77%) the release of [3H]-arachidonic acid from neutrophils stimulated with fMLP.
      The peptide, however, did not inhibit the up-regulation of the beta 2-integrin
      CD11b and the concomitant shedding of L-selectin from neutrophil plasma membrane
      induced by fMLP. In adhesion experiments, human Ac2-26 inhibited neutrophil
      adhesion to endothelial monolayers when this was stimulated with fMLP, but not
      when this followed endothelial cell activation with histamine or platelet
      activating factor. Again, the effect of the peptide was concentration-dependent,
      and an approximate EC50 of 33 microM was calculated. When a preparation of 125I
      labeled human Ac2-26 was incubated with the neutrophils, the peptide was
      internalised in an energy-dependent fashion. All together, these observations
      lead us to propose a model in which this peptide derived from the N-terminus of
      human lipocortin 1 alters a common cellular mechanism producing a selective
      inhibition of neutrophil activation.

PMID- 7575658
TI  - Inhibition of nitric oxide (NO.) production in murine macrophages by flavones.
AB  - The effect of flavone (2-phenylbenzopyran-4-one) and three amino-substituted
      flavones on the production of nitrite by murine activated peritoneal macrophages
      was studied in vitro. Activated peritoneal macrophages obtained from mice pre
      treated with concanavalin A (Con A) (in vivo), after exposure in vitro to
      lipopolysaccharide (LPS) at a concentration of 100 ng/ml, produced nitrite (20.3
      +/- 2.5 nmol/10(6) cells), as measured after 24 hr by the Griess reaction.
      Stimulation of production of nitrite was inhibited by NG-monomethyl-L-arginine,
      suggesting that nitrite was formed via nitric oxide (NO.) as a product of
      metabolism of arginine. Stimulation was inhibited by flavone and the
      aminoflavones (20-100 microM). 3'-amino-4'-hydroxyflavone was the most potent
      inhibitor of nitrite production. Genistein (5,7-dihydroxy- 3-(4-hydroxy-phenyl)
      4H-1-benzopyran-4-one) also inhibited production of nitrite, by a mechanism that
      appears not to involve protein tyrosine kinases. These results suggest that the
      flavones can modulate the immune responses and the inflammatory reactions by
      controlling production of nitric oxide.

PMID- 7575660
TI  - The intracellular phosphorylation of (-)-2'-deoxy-3'-thiacytidine (3TC) and the
      incorporation of 3TC 5'-monophosphate into DNA by HIV-1 reverse transcriptase and
      human DNA polymerase gamma.
AB  - (-)-2'-deoxy-3'-thiacytidine (3TC) has been shown to be a potent, selective
      inhibitor of HIV replication in vitro, which requires phosphorylation to its 5'
      triphosphate for antiviral activity. The intracellular concentration of 3TC 5'
      triphosphate in phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes
      (PBL) shows a linear dependence on the extracellular concentration of 3TC up to
      an extracellular 3TC concentration of 10 microM. At this extracellular
      concentration of 3TC, the resulting intracellular concentration of 3TC 5'
      triphosphate is 5 microM. This value is similar to the inhibition constant (Ki)
      values for the competitive inhibition of human immunodeficiency virus type 1 (HIV
      1) reverse transcriptase and human DNA polymerases (10-16 microM) by 3TC 5'
      triphosphate. Since the concentration of 3TC producing 90% inhibition (IC90) of
      HIV replication in PBLs has been reported to be 76 nM, the antiviral activity of
      3TC requires intracellular concentrations of 3TC 5'-triphosphate, which would
      result in very little inhibition of reverse transcriptase if its sole mode of
      action was competitive inhibition. This apparent discrepency may be explained by
      the ability of 3TC 5'-triphosphate to act as a substrate for reverse
      transcriptase. Primer extension assays have shown that 3TC 5'-triphosphate is a
      substrate for HIV-1 reverse transcriptase and DNA polymerase gamma, resulting in
      the incorporation of 3TC 5'-monophosphate into DNA. In the case of DNA polymerase
      gamma, the product of this reaction (i.e. double-stranded DNA with 3TC 5'
      monophosphate incorporated at the 3'-terminus of the primer strand) is also a
      substrate for the 3'-5' exonuclease activity of this enzyme. This may explain the
      low levels of mitochondrial toxicity observed with 3TC.

PMID- 7575661
TI  - Structure-activity relationships of phenothiazines in inhibiting lymphocyte
      motility as determined by a novel flow cytometric assay.
AB  - Lymphocyte motility is highly dependent on rapid changes in cell shape. The human
      T-lymphoma cell line, MOLT-4, is constitutively shape-changing and motile, and
      both of these properties can be inhibited by the phenothiazine, chlorpromazine,
      as assessed by video analysis and migration across polycarbonate filters. In this
      paper, the light-scattering facility of a flow cytometer has been used to
      establish a simpler and more quantitative means of measuring changes in shape. By
      this method, the structure activity relationship (SAR) of phenothiazines and
      related compounds has been determined. The most active compounds had the
      tricyclic phenothiazine nucleus with a constrained dialkylaminoalkyl substituent
      at the nitrogen. The SAR for inhibition of lymphocyte motility differs from those
      reported for neuroleptic effects and for inhibition of PKC or calmodulin.
      Phenothiazine concentrations that inhibited lymphocyte shape-changing resulted in
      reduced F-actin concentrations. This indicates that the probable mode of action
      is disruption of mechanisms regulating actin polymerisation.

PMID- 7575662
TI  - Inhibition of oxidative insult in cultured cells by a novel 6-chromanol
      containing antioxidant.
AB  - N18-RE-105 neuronal hybridoma cells were used in a cell culture system to
      evaluate the protective effects of a novel 6-chromanol-containing antioxidant,
      U78517F. First, the incorporation of the compound into the cells was evaluated,
      using a serum albumin carrier. Then the cells were exposed to peroxide-generating
      compounds, and the cell injury was estimated from the loss of alpha
      aminoisobutyric acid (AIB) transport. We found that U78517F only protected the
      cells significantly when the degree of oxidative insult was below a certain
      limit; the measurable protection of cells by U78517F against either cumene
      hydroperoxide or H2O2 was limited to a narrow range of concentrations of the
      reactive oxygen species generator. Additionally, the protection provided by
      U78517F was largely localized to the cell membrane and did not extend to
      protection of mitochondrial function. The action of U78517 was fully consistent
      with a direct radical scavenging in the cells. The results indicate that the
      following factors must be taken into account for evaluation of antioxidants in
      cell culture: (a) the delivery of a compound to cells, especially when the
      compound is lipophilic; (b) the nature and extent of the oxidative insult used to
      evaluate protection; and (c) the location of the protective agent in the cells.

PMID- 7575663
TI  - Role of prostaglandin E2 in alterations of the beta-adrenergic system from rat
      eclamptic uterus.
AB  - The inotropic effect of isoproterenol, as well as the beta-adrenoceptor
      population, was measured in pregnant uterine tissue from female spontaneous
      hypertensive rats (SHR) (control group: C) and female SHR that were grafted with
      skin from Holtzman male rats (eclamptic group: E). The Kd value of the
      concentration-response curve of isoproterenol was higher for uteri from E rats
      than C rats. This phenomenon was not accompanied by a modification in the
      expression of beta-adrenoceptors. Inhibition of the synthesis of prostaglandins
      prevented the hyporeactivity to isoproterenol during eclampsia. Moreover, uteri
      from E rats generated and released greater amounts of prostaglandin E2 (PGE2)
      than uteri from C rats, even in the presence or absence of isoproterenol. In
      addition, whereas isoproterenol administered alone increased basal cyclic AMP
      (cAMP) production from C uteri, PGE2 administered alone enhanced cAMP production
      in E uterine tissue. These results suggest that the decrease in beta-adrenergic
      response to the agonist in E rats is ascribed to PGE2 production. The abnormal
      reactivity to the beta-agonist could be associated with a heterologous
      desensitization of uterine beta-adrenoceptors exerted by PGE2 overload in uteri
      from E rats. These results bear directly on the regulation of uterine motility
      during pregnancy, since an impaired response to beta-adrenergic innervation could
      lead to increased uterine motility, impairing the maintenance of pregnancy.

PMID- 7575664
TI  - Effect of cholephilic dyes on hepatic tight junctional permeability in the rat.
AB  - Changes in biliary permeability during cholephilic dye-induced choleresis, as
      assessed by measuring the movement into bile of two permeability probes,
      [14C]sucrose and horseradish peroxidase, were analyzed following an i.v. infusion
      (60 nmol/min per 100 g body wt) of the model cholephilic organic anion
      sulfobromophthalein in rats. Dye infusion led to a progressive increase of the
      [14C]sucrose bile-to-plasma ratio, which reached a maximum value after 100 min of
      dye infusion (+97%). Paracellular entry of horseradish peroxidase, as evaluated
      by the early peak of its biliary appearance curve, was also selectively increased
      (+69%), without changes in the later (transcytotic) access of the protein.
      Additional dose-response studies of biliary permeability to [14C]sucrose, using
      sulfobromophthalein and rose bengal, showed that this effect was dose-dependent
      and rapidly reversed by interruption of dye administration. The influence of
      hydrophobic/hydrophilic balance on this effect was also studied by infusing four
      dyes covering a broad range of hydrophobicity (phenol red, bromocresol green,
      sulfobromophthalein, and rose bengal), so as to attain a similar value of dye
      hepatic content at the end of the experiment (approximately 150 nmol/g liver wt).
      Under these conditions, a strong positive correlation was found between the
      increase in biliary permeability to [14C]sucrose and dye hydrophobicity. These
      results suggest that cholephilic dyes increase tight junctional permeability in a
      reversible and dose-dependent manner, and that this effect depends on the
      hydrophobic/hydrophilic balance of the dye.

PMID- 7575665
TI  - Comparison of aza-anthracenedione-induced DNA damage and cytotoxicity in
      experimental tumor cells.
AB  - Aza-anthracenediones are a new class of anti-cancer drugs, which demonstrate
      promising in vitro and in vivo activity. Our laboratory has synthesized a variety
      of structural analogs in which we determined previously that the positioning of
      the nitrogen within the backbone, as well as sidearm modification, results in
      dramatic differences in the potency of cytotoxicity. We reported previously that
      although DNA reactivity appears to be a necessary component for mediating cell
      death, it is not sufficient for predicting cytotoxicity of the aza
      anthracenediones. We have chosen three aza-anthracenediones (BBR 2828, BBR 2778
      and BBR 2378) to investigate the importance of DNA strand breaks and/or protein
      concealed DNA breaks induced by aza-anthracenediones. We determined in the
      present study that, while all three drugs cause DNA breaks as determined by
      alkaline and neutral elution, as well as KCl-SDS precipitation, these breaks do
      not correlate directly with their potency as cytotoxic compounds. Further, we
      found significant differences in the types of DNA breaks induced by these drugs.
      Finally, we report that the persistence of protein-DNA complexes induced by all
      three drugs was similar and, therefore, cannot account for differences in the
      potency of cytotoxicity of the aza-anthracenediones. Thus, we postulate that,
      while the total number of drug-induced protein-concealed DNA breaks is an
      important indicator of drug toxicity, it is possible that the actual nature of
      the breaks may differ among the aza-anthracenedione congeners, and it is these
      differences in the actual proteins present in the DNA breaks that differentiate
      between aza-anthracenediones.

PMID- 7575667
TI  - Differential cytotoxic effects of mizoribine and its aglycone on human and murine
      cells and on normal and enzyme-deficient human cells.
AB  - The growth inhibitory mechanisms of mizoribine, an immunosuppressive imidazole
      nucleoside used clinically to inhibit rejection reactions after renal
      transplantation and in the treatment of systemic lupus erythematosus and
      rheumatoid arthritis, were studied in human and murine cells. We found that (a)
      human cells were 20- to 60-fold more resistant than murine cells to both
      mizoribine and its aglycone, (b) adenine phosphoribosyltransferase (APRT)
      deficient human cells were resistant to aglycone but not to mizoribine, (c)
      hypoxanthine phosphoribosyltransferase (HPRT)-deficient human cells were at least
      100-fold more sensitive to both mizoribine and aglycone, and (d) the decrease in
      intracellular GTP broadly paralleled the cytotoxicity in each case. Therefore,
      data obtained from studies using non-human tissues should be interpreted
      carefully before clinical application. Results indicate that the growth
      inhibitory effect of the aglycone but not of mizoribine is mediated by APRT, and
      depletion of guanine nucleotides is responsible for the effects of both drugs.
      Our data also suggest that the drugs may reduce mutant HPRT-deficient somatic
      cells in vivo, and may cause enhanced adverse reactions in HPRT-deficient
      individuals. The drug may have altered effects in patients receiving other purine
      or pyrimidine analogs.

PMID- 7575666
TI  - The IMP dehydrogenase inhibitor mycophenolic acid antagonizes the CTP synthetase
      inhibitor 3-deazauridine in MOLT-3 human leukemia cells: a central role for
      phosphoribosyl pyrophosphate.
AB  - Mycophenolic acid, an inhibitor of the enzyme IMP dehydrogenase, antagonizes the
      CTP synthetase inhibitor 3-deazauridine in its anti-proliferative effects on MOLT
      3 human T leukemia cells. No depletion of CTP occurred, and decreased amounts of
      3-deazuridine-triphosphate were measured in cells incubated with mycophenolic
      acid and 3-deazuridine. Most probably, these phenomena are related to the
      increased amounts of PRPP observed, which can result in an increased pyrimidine
      biosynthesis de novo and, as a consequence, a decreased metabolism of 3
      deazauridine via the salvage pathway.

PMID- 7575668
TI  - Changes in the cellular distribution of lipocortin-1 (Annexin-1) in C6 glioma
      cells after exposure to dexamethasone.
AB  - Glucocorticoid-induced changes in cellular levels of Lipocortin-1 (LC-1) (Annexin
      1) in C6 glioma cells were determined by electrotransfer and immunoblotting
      techniques. Separate cell protein fractions were prepared to study the influence
      of the glucocorticoid steroid, dexamethasone, on LC-1 localisation. Cells were
      grown in steroid-depleted medium and exposed to dexamethasone (10(-8) and 10(-7)
      M) for 2, 6, and 16 hr. The glucocorticoid-dependent changes in cellular content
      of LC-1 were both dose- and time-related. Increases above control levels in
      intracellular and extracellular LC-1 content were detected with the greatest
      changes occurring at the cell surface. The glucocorticoid-dependent alteration in
      LC-1 distribution in C6 glioma cells was attenuated by the protein synthesis
      inhibitor, cycloheximide, indicating the involvement of de novo LC-1 synthesis.
      The significance of these results is discussed in relation to the current concept
      that some of the anti-inflammatory effect of glucocorticoids occurs through the
      action of extracellular LC-1.

PMID- 7575670
TI  - The bioactivation of amodiaquine by human polymorphonuclear leucocytes in vitro:
      chemical mechanisms and the effects of fluorine substitution.
AB  - Amodiaquine, a 4-aminoquinoline antimalarial, has been associated with hepatitis
      and agranulocytosis in humans. Drug hypersensitivity reactions, especially
      agranulocytosis, have been attributed to reactive intermediates generated by the
      oxidants discharged from stimulated polymorphonuclear leucocytes (PMN). The
      metabolism of amodiaquine to both stable and chemically reactive metabolites by
      human PMN has been investigated in vitro. Incubation of [14C]-amodiaquine with
      PMN resulted in irreversible binding of radiolabel to protein and depletion of
      intracellular reduced glutathione, which were enhanced by phorbol myristate
      acetate (PMA), a PMN activator. Two metabolites were identified: the C-5'
      glutathione adduct of amodiaquine, derived from both endogenous and exogenous
      glutathione, and 4-amino-7-chloroquinoline, which was presumed to be formed by
      hydrolysis of amodiaquine quinoneimine. Desethylamodiaquine, the major plasma
      metabolite of amodiaquine in humans, also underwent bioactivation to a chemically
      reactive species in the presence of PMA-stimulated PMN. Substitution of the 4'
      hydroxyl group in amodiaquine with fluorine significantly reduced irreversible
      binding to protein and abolished depletion of intracellular glutathione in the
      presence of PMA. These findings indicate that the bioactivation of amodiaquine by
      PMN is associated with the formation of a quinoneimine intermediate. Such a
      reactive metabolite, if produced in PMN or bone marrow in vivo, may be
      responsible for the drug's myelotoxicity.

PMID- 7575669
TI  - The new oral hypoglycemic agent, CS-045, inhibits the lipid peroxidation of human
      plasma low density lipoprotein in vitro.
AB  - Several lines of evidence have revealed that the oxidative modification of low
      density lipoprotein (LDL) is probably associated with the genesis of the
      atherosclerotic region. CS-045 is a new (thiazolidine) class of oral hypoglycemic
      agent which has a hindered phenol in the side chain (an analogue of alpha
      tocopherol). The present results indicate that CS-045 had a relatively high
      antioxidative potency in inhibiting the lipid peroxidation of human plasma LDL in
      vitro induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) compared
      with that of alpha-tocopherol. These findings suggest that CS-045 may be useful
      in preventing the progression of atherosclerosis in diabetic patients.

PMID- 7575671
TI  - Immunohistochemistry of drug-metabolizing enzymes.

PMID- 7575673
TI  - Regulation of prostaglandin H synthase 2 expression in human monocytes by the
      marine natural products manoalide and scalaradial. Novel effects independent of
      inhibition of lipid mediator production.
AB  - The marine natural products manoalide and scalaradial are potent anti
      inflammatory agents that inactivate the enzyme phospholipase A2 (PLA2) in vitro.
      To study the mechanism of inhibition of prostaglandin E2 (PGE2) production in
      human monocytes by manoalide and scalaradial, lipopolysaccharide (LPS)-induced
      prostaglandin biosynthesis and induction of prostaglandin H synthase (PGHS) were
      evaluated. LPS (10 ng/mL) and interleukin-1 beta (IL-1 beta, 50-1000 ng/mL) but
      not tumor necrosis factor alpha (TNF alpha, 300 ng/mL) induced the expression of
      the PGHS-2 isoform as determined by immunoblot analysis with a specific
      polyclonal antibody for PGHS-2. Manoalide and scalaradial (1-10 microM) inhibited
      LPS-induced endogeneous PGE2 production, reduced the LPS-induced PGHS activity,
      and reduced the expression of PGHS-2. Indomethacin [a PGHS inhibitor (0.01 to 0.1
      microM)], zileuton [a 5-lipoxygenase inhibitor (3-10 microM)], and WEB-2806 [a
      platelet-activating factor (PAF) antagonist (30 microM)] did not affect the LPS
      induced expression of PGHS-2 in human monocytes. These results suggest that
      modulation of lipid mediator production by manoalide or scalaradial may not be
      involved in the observed effects on the expression of PGHS-2. Manoalide and
      scalaradial also inhibited the release of IL-1 beta and TNF alpha from LPS
      stimulated monocytes. Expression of PGHS-2 induced by either LPS or IL-1 beta was
      blocked by the IL-1 receptor antagonist (IL-1ra, 2 micrograms/mL) but not by
      rolipram, a phosphodiesterase IV inhibitor that inhibits TNF alpha but not IL-1
      beta release. Similar to LPS, IL-1 beta-induced PGHS-2 expression was apparently
      not regulated by lipid mediators such as prostaglandins, leukotrienes or PAF as
      determined with specific inhibitors and antagonists. Scalaradial and to some
      extent manoalide were capable of blocking the IL-1 beta-induced expression of
      PHGS-2. These results indicate that IL-1 beta is the predominant cytokine
      responsible for the induction of PGHS-2 in the human monocyte. Furthermore,
      marine natural products such as scalaradial have novel effects on the IL-1 beta
      mediated induction of PGHS-2 in human monocytes, which appears to be independent
      of effects on lipid mediator production.

PMID- 7575674
TI  - Inhibition of all-trans-retinoic acid metabolism by fluconazole in vitro and in
      patients with acute promyelocytic leukemia.
AB  - All-trans-retinoic acid induces acute promyelocytic leukemia cell differentiation
      in vitro, and it produces greater than 90% complete remissions in patients with
      acute promyelocytic leukemia. Despite the high response rate, the majority of
      patients relapse with continued trans-retinoic acid therapy, and disease
      progression has been observed to be accompanied by an increase in the metabolism
      of trans-retinoic acid in the patients. In this study, the pharmacokinetic
      disposition of trans-retinoic acid was determined by HPLC in patients with acute
      promyelocytic leukemia before and after concurrent therapy with the triazole
      antimycotic agent fluconazole. Treatment with trans-retinoic acid for 1 week
      reduced the area under the plasma trans-retinoic acid concentration vs time curve
      in one patient by 67%, from 277 to 91 ng/mL/hr. Trans-retinoic acid
      pharmacokinetics were repeated after the second dose of fluconazole, administered
      1 hour prior to the retinoid, and the AUC was found to be 401 ng/mL/hr, a greater
      than 4-fold increase from the pre-fluconazole level. A similar, though more
      modest, effect of fluconazole was seen in a second acute promyelocytic leukemia
      patient. The effect of fluconazole on trans-retinoic acid metabolism was examined
      in vitro using isolated human hepatic microsomes. Fluconazole inhibited the NADPH
      dependent cytochrome P450-mediated catabolism of trans-retinoic acid in a
      concentration-dependent manner. Although fluconazole was approximately one-half
      as potent an inhibitor when compared with ketoconazole, a related antifungal
      drug, 60-90% inhibition was observed at the concentrations of fluconazole
      measured in the acute promyelocytic leukemia patients. Neither fluconazole nor
      ketoconazole inhibited lipid hydroperoxide-mediated metabolism of trans-retinoic
      acid. Since fluconazole is a well-tolerated agent frequently administered to
      leukemia patients, its use in combination with trans-retinoic acid merits further
      consideration.

PMID- 7575672
TI  - Effects of metalloproteinase inhibitors on leukotriene A4 hydrolase in human
      airway epithelial cells.
AB  - Human neutrophil leukotriene A4 (LTA4) hydrolase is a zinc-containing
      metalloproteinase with aminopeptidase activity and can be inhibited by some
      metalloproteinase inhibitors. Human airway epithelial cells also contain an LTA4
      hydrolase enzyme that has some novel properties, suggesting that this enzyme may
      be functionally and structurally unique. Thus, we questioned whether the
      epithelial cells were studied either intact or disrupted. Of the
      metalloproteinase inhibitors examined, only captopril, bestatin, and fosinoprilat
      had appreciable inhibitory activity for LTA4 hydrolase in disrupted epithelial
      cells. Concentration-inhibition curves to captopril, bestatin, and fosinoprilat
      revealed IC50 values of 430 microM, 7 microM, and 1 mM, respectively, for
      disrupted-cell LTA4 hydrolase activity. In contrast to its effects on
      neutrophils, 1,10-O-phenanthroline had no significant effect on disrupted
      epithelial cell hydrolase activity and had only minimal effects when this
      activity was partially purified (179-fold). LTA4 hydrolase concentration
      inhibition curves examined in intact cells with captopril, bestatin, and 1,10-O
      phenanthroline revealed IC50 values of 63, 70, and 920 microM, respectively.
      Aminopeptidase activity in disrupted epithelial cells was inhibited by amastatin,
      bestatin, and 1,10-O-phenanthroline (IC50 values of 500 nM, 1 microM, and 17
      microM, respectively), but not by captopril at the highest concentration tested,
      10 mM. These findings are in contrast to prior studies in neutrophils. When
      neutrophils were stimulated with A23187 after treatment with captopril,
      transcellular synthesis of LTB4 was inhibited more effectively than direct
      synthesis of leukotriene B4 (LTB4) (43.8 +/- 2.5 vs 18.5 +/- 4.7%; N = 8, P <
      0.02). We conclude that LTA4 hydrolase activity of human airway epithelial cells
      is inhibited by some metalloproteinase inhibitors, but that the profile of
      inhibition is distinct from that for the neutrophil enzyme. These data provide
      additional information that LTA4 hydrolase in the epithelial cell is a novel
      enzyme, distinct from that found in the neutrophil.

PMID- 7575675
TI  - Diquat-dependent protein carbonyl formation. Identification of lipid-dependent
      and lipid-independent pathways.
AB  - In a previous report on diquat-dependent oxidative damage in rat hepatic
      microsomes, protein oxidation, as measured by protein carbonyl (PC) formation,
      was observed in addition to lipid peroxidation (LP). Both phenomena were
      antioxidant sensitive. Inhibition of PC formation was somewhat surprising given
      the proposed mechanism of metal-catalyzed protein oxidation. Studies reported
      here examined diquat-dependent PC formation in greater detail. In rat hepatic
      microsomes, diquat-dependent thiobarbituric acid-reactive substances (TBARS) and
      PC formation were time and concentration dependent. In this system, LP was
      inhibited completely by U-74006F or U-78517G, whereas PC formation was inhibited
      only partially by these antioxidants. In an essentially lipid-free system
      consisting of purified rat hepatic cytochrome P450 reductase, BSA and an NADPH
      generating system, PC formation was also observed, but was not antioxidant
      sensitive. Under these conditions, minimal diquat-dependent TBARS formation was
      observed. The observation of relative antioxidant insensitivity is consistent
      with H2O2 (generated during the diquat redox cycle) catalyzing protein oxidation
      via a site-specific, metal-catalyzed mechanism. Thus, different pathways would
      appear to be involved in diquat-dependent PC formation in lipid-containing and
      lipid-free systems. Carbon tetrachloride induces LP following reductive
      activation to the trichloromethyl free radical, a pathway not directly involving
      H2O2 generation. In the microsomal system, CCl4 induced TBARS and PC formation,
      both of which were completely inhibitable by antioxidants. Taken together, these
      data suggest that diquat induces PC formation by lipid-dependent (antioxidant
      sensitive) and lipid-independent (antioxidant-insensitive) pathways. In
      microsomes, both pathways contribute to diquat-dependent PC formation. Data for
      the lipid-independent pathway are consistent with the mechanism of metal
      catalyzed protein oxidation proposed by Stadtman and colleagues (reviewed in Free
      Radic Biol Med 9: 315-325, 1990), while the lipid-dependent pathway is likely
      secondary to LP itself--via a Michael-type addition reaction between
      hydroxyalkenals and protein sulfhydryl groups, amino groups or other protein
      nucleophiles. The latter pathway is also responsible for carbon tetrachloride
      dependent PC formation. Additional studies are in progress to further
      characterize the lipid-independent mechanism.

PMID- 7575676
TI  - Antitrypanosomal activity of camptothecin analogs. Structure-activity
      correlations.
AB  - African trypanosomes (Trypanosoma brucei species) are parasitic protozoa that
      cause lethal diseases in humans and cattle. Previous studies showed that
      camptothecin, a potent and specific inhibitor of DNA topoisomerase I, is
      cytotoxic to African trypanosomes and related pathogenic hemoflagellates (Bodley
      AL and Shapiro TA, Proc Natl Acad Sci USA 92: 3726-3730, 1995). In this study, a
      series of camptothecin analogs was tested against axenically cultured,
      bloodstream form, T. brucei. Modifications to the pentacyclic nucleus of
      camptothecin ablated antiparasitic activity. In contrast, activity could be
      increased by substituents added to the parent ring system (e.g. 10,11
      methylenedioxy or ethylenedioxy groups; alkyl additions to carbon 7; or 9-amino
      or 9-chloro substituents). Cytotoxicity was correlated with the level of
      cleavable complexes in trypanosomes, implicating topoisomerase I as the
      intracellular target for these compounds. To obtain some indication of selective
      toxicity, ten compounds were also tested against L1210 mouse leukemia cells. The
      9-substituted-10,11-methylenedioxy analogs caused a disproportionate increase in
      antiparasitic activity, compared with mammalian cell toxicity. These findings
      provide a basis for designing further structural modifications and for selecting
      camptothecin analogs to test in animal models of trypanosomiasis.

PMID- 7575677
TI  - Metabolism and blood-brain clearance of L-3,4-dihydroxy-[3H]phenylalanine
      ([3H]DOPA) and 6-[18F]fluoro-L-DOPA in the rat.
AB  - 6-[18F]fluoro-L-DOPA (FDOPA) has been used as a tracer for the cerebral activity
      of L-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron
      emission tomography (PET). However, the substitution of fluorine on the aromatic
      ring may alter the disposition and metabolism of FDOPA from that of endogenous
      DOPA. In the present study, the kinetics of the peripheral metabolism and the
      facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were
      compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was
      O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA
      in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated
      from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The
      mean unidirectional blood-brain clearance of FDOPA (4.5 mL.hg-1.min-1) in six
      brain regions was 60% higher than that of [3H]DOPA.

PMID- 7575678
TI  - Down-regulation of epidermal growth factor-induced 12-lipoxygenase expression by
      glucocorticoids in human epidermoid carcinoma A431 cells.
AB  - The effect of glucocorticoids on epidermal growth factor (EGF)-induced expression
      of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. A
      significant suppression of the EGF-induced expression of 12-lipoxygenase was
      observed in cells pretreated with 1 microM dexamethasone for 2 hr. The same
      pretreatment for 8 hr resulted in 55 and 54% inhibition of EGF-induced 12
      lipoxygenase activity and mRNA expression, respectively. Cortisol, but not sex
      and mineral steroids, had a similar inhibitory effect. The glucocorticoid
      antagonist RU486 completely blocked the inhibitory effect of dexamethasone,
      suggesting that the action of dexamethasone was mediated through the ligation of
      glucocorticoid receptors. The results indicated that pretreatment of A431 cells
      with glucocorticoids resulted in a down-regulation of the EGF-induced expression
      of 12-lipoxygenase at the mRNA and enzyme activity level, which was mediated
      through glucocorticoid receptor activation.

PMID- 7575679
TI  - A QSAR study comparing the cytotoxicity and DNA topoisomerase II inhibitory
      effects of bisdioxopiperazine analogs of ICRF-187 (dexrazoxane).
AB  - A series of twelve structurally related bisdioxopiperazines that included ICRF
      187 (dexrazoxane), ICRF-159 (razoxane), ICRF-193, and ICRF-154 were examined both
      for their ability to inhibit the growth of Chinese hamster ovary (CHO) cells and
      their ability to inhibit the catalytic activity of mammalian DNA topoisomerase
      II. The bisdioxopiperazines exhibited a wide range in both growth inhibitory
      effects (30,000-fold), and in their ability to inhibit the catalytic activity of
      topoisomerase II (150-fold). The cytotoxicity of the bisdioxopiperazines toward
      CHO cells was highly correlated (correlation coefficient r = 0.86, P = 0.0003)
      with their inhibition of the catalytic activity of DNA topoisomerase II. This
      result strongly suggests that DNA topoisomerase II is the functional target of
      the bisdioxopiperazines. The stereoisomers (+)-ICRF-187 and (-)-ICRF-186 were
      observed to be equally cytotoxic and equally inhibitory toward DNA topoisomerase
      II. This result indicates that the bisdioxopiperazine binding site on DNA
      topoisomerase II is large enough or flexible enough to accommodate either form of
      the drug. The strongly metal-ion binding fully rings-opened hydrolysis product of
      ICRF-187, ADR-925, demonstrated no measurable inhibitory activity toward DNA
      topoisomerase II or cytotoxicity toward CHO cells.

PMID- 7575680
TI  - Suramin modulates cellular levels of hepatocyte growth factor receptor by
      inducing shedding of a soluble form.
AB  - Several growth factor receptors undergo shedding from the cell surface as a
      result of limited proteolysis via mechanisms that are at present poorly
      understood. By Western blotting of the conditioned media and cell lysates of
      several cell lines expressing the hepatocyte growth factor receptor, we found
      that suramin, a pharmacological agent that inhibits the activity of many growth
      factors, was able to induce shedding of this receptor. Increased levels of
      soluble hepatocyte growth factor receptor were observed in the conditioned media
      of GTL-16, a cell line over-expressing the receptor, as early as ten minutes
      after initial exposure to the agent, and incubation of this line with 300 microM
      suramin caused a 50% reduction in cell-associated levels of receptor after 6
      hours. Although protein kinase C activation by treatment of cells with phorbol
      esters has previously been found to stimulate shedding of the hepatocyte growth
      factor receptor, this hitherto undescribed activity of suramin was not affected
      by protein kinase C inhibitors. Since shedding represents a possible means of
      down-modulation of receptor activity, suramin may inhibit the hepatocyte growth
      factor ligand/receptor system, not only by abrogation of hepatocyte growth factor
      binding to intact receptor, but also by induction of receptor shedding.

PMID- 7575681
TI  - The P-glycoprotein-mediated relative decrease in cytosolic free drug
      concentration is similar for several anthracyclines with varying lipophilicity.
AB  - We have used a new methodology to measure the activity of P-glycoprotein (P-gp)
      in multidrug-resistant (MDR) tumor cells. This activity leads to a lower
      cytosolic concentration and a lower cytotoxicity of the classical anthracyclines,
      daunorubicin (DNR), and doxorubicin (DOX). It has been reported that the
      anthracycline idarubicin (IDA), which is more lipophilic, has a higher clinical
      efficacy in acute myeloid leukemias (AML) than DNR and DOX. In our study, the aim
      was to determine for a series of anthracyclines how variations in the passive
      drug influx rate as well as the P-gp-mediated drug pumping rate affect their
      cytosolic free drug concentrations and how these parameters are related to drug
      cytotoxicity. We selected six anthracyclines: DOX, DNR, epidoxorubicin (EPI),
      IDA, cyano-morpholino-doxorubicin (CMD), and carminomycin (CAR), ordered
      according to their increasing octanol/PBS buffer concentration ratios,
      respectively. To measure the passive permeation coefficient, the P-gp-mediated
      drug pumping rate, and the cytosolic free drug concentration, we used a flow
      through system in which cells were exposed to a flowing medium containing drugs.
      We used the MDR P-gp-containing cell line KB8-5. It was shown that the passive
      drug permeation coefficient as well as the drug pumping rate of P-gp increased
      with increasing lipophilicity in this series of anthracyclines. The cytosolic
      free drug concentration was lowered by P-gp to a similar extent in KB8-5 cells
      for all drugs tested (40-50% of the extracellular drug concentration). CMD, IDA,
      and CAR had lower IC50 values and lower resistance factors in comparison to DOX,
      DNR, and EPI. Verapamil reversed the resistance for all anthracyclines tested. In
      conclusion, for several anthracyclines the activity of P-gp leads to a similar
      relative decrease in the cytosolic free drug concentration; consequently, the
      reported lower resistance factor of IDA compared to that of DNR is not due to the
      inability of P-gp to export IDA from cells.

PMID- 7575682
TI  - Ryanodine as inhibitor of chemotactic peptide-induced chemotaxis in human
      neutrophils.
AB  - Ryanodine gave a moderate inhibition of chemotactic peptide-activated chemotaxis
      by intact human neutrophils. Chemotaxis by electroporated neutrophils was
      strongly inhibited in the nanomolar concentration range. Inhibition of chemotaxis
      by electroporated neutrophils occurs at concentrations known to open calcium
      channels in ryanodine-sensitive Ca2+ stores. Whereas migration by formyl
      methionyl-leucyl-phenylalanine (fMLP)- or interleukin-8-activated electroporated
      neutrophils was strongly inhibited by ryanodine, chemotaxis induced by protein
      kinase C activators was not affected. This suggests that the importance of
      ryanodine-sensitive Ca2+ stores for migration depends on the type of activator
      used. Ryanodine gave an increase of cytoplasmic free calcium due to the
      liberation of calcium from internal stores and to the influx of extracellular
      calcium. The results show that the neutrophil contains ryanodine-sensitive
      calcium stores that might be involved in receptor-mediated chemotaxis.

PMID- 7575683
TI  - Role of gamma-glutamyltransferase in putrescine uptake by rat type II
      pneumocytes.
AB  - Putrescine uptake in type II pneumocytes is a carrier-mediated active process.
      Our hypothesis was that oligoamines might be taken up into the cell at least in
      part by gamma-glutamyltransferase (gamma-GT). This was investigated in rat type
      II pneumocytes 24 hr after their isolation. Preexposure to 125 microM L
      buthionine-[SR]-sulfoximine (BSO) or 100 microM diethylmaleate (DEM), both of
      which affect intracellular glutathione (GSH) only, were found to decrease GSH by
      85% (p < 0.05) and 62%, respectively (p < 0.05), without change in [3H]
      putrescine uptake. Preexposure to 20 microM N-ethylmaleimide (NEM), which affects
      intra- and extracellular GSH, decreased intracellular GSH by 79% (p = 0.015) and
      putrescine uptake by 39% (p = 0.03). Selective extracellular GSH depletion by 10
      microM copper-o-phenanthroline complex (CuP) led to a decrease in putrescine
      uptake of 41% (p = 0.001), while intracellular GSH remained unchanged. Specific
      inhibition of gamma-GT by 5-20 mM serine-borate or 5 mM acivicin gave similar
      degrees of putrescine uptake inhibition (39.5% and 40.5%). The kinetic properties
      of the putrescine uptake system in the presence of acivicin and serine-borate
      indicated that the Vmax decreased by 25%, while Km remained unchanged. In
      experiments with pure gamma-GT, the oligoamines putrescine, spermidine and
      spermine, and cystamine proved to be acceptor substrates for gamma-GT, all having
      similar efficiencies (Vmax/Km); methylglyoxal-bis-(guanyl-hydrazone) and paraquat
      were not accepted. As extracellular GSH is required for gamma-GT, and because its
      extracellular depletion inhibits putrescine uptake as much as specific inhibition
      of gamma-GT, we suggest that 30-40% of the putrescine uptake in type II
      pneumocytes occurs by gamma-GT and that, therefore, at least two systems are
      involved in the uptake of putrescine.

PMID- 7575685
TI  - The economic cost and social and psychological impact of musculoskeletal
      conditions. National Arthritis Data Work Groups.
AB  - OBJECTIVE: To provide an indication of the economic, social, and psychological
      impact of musculoskeletal conditions in the United States. METHODS: Review of the
      literature combined with estimates of data concerning health care utilization and
      acute and chronic disability due to musculoskeletal conditions, from the 1990
      1992 National Health Interview Survey. RESULTS: The cost of musculoskeletal
      conditions was $149.4 billion in 1992, of which 48% was due to direct medical
      care costs and the remainder was due to indirect costs resulting from wage
      losses. This amount translates to approximately 2.5% of the Gross National
      Product, a sharp rise since the prior studies, even if part of the increase is an
      artifact of improved accounting methods. Each year, persons with musculoskeletal
      conditions make 315 million physician visits, have more than 8 million hospital
      admissions, and experience approximately 1.5 billion days of restricted activity.
      Approximately 42% of persons with musculoskeletal conditions--more than 17
      million in all--are limited in their activities. CONCLUSION: The economic and
      social costs of musculoskeletal conditions are substantial. These conditions are
      responsible for a sizable amount of health care use and disability, and they
      significantly affect the psychological status of the individuals with the
      conditions as well as their families.

PMID- 7575684
TI  - Protection of hypoxia-induced ATP decrease in endothelial cells by ginkgo biloba
      extract and bilobalide.
AB  - Due to their localization at the interface between blood and tissue, endothelial
      cells are the first target of any change occurring within the blood, and
      alterations of their functions can seriously impair organs. During hypoxia, which
      mimics in vivo ischemia, a cascade of events occurs in the endothelial cells,
      starting with a decrease in ATP content and leading to their activation and
      release of inflammatory mediators. EGb 761 and one of its constituents,
      bilobalide, were shown to inhibit the hypoxia-induced decrease in ATP content in
      endothelial cells in vitro. Under these conditions, glycolysis was activated, as
      evidenced by increased glucose transport, as well as increased lactate
      production. Bilobalide was found to increase glucose transport under normoxic but
      not hypoxic conditions. In addition, EGb and bilobalide prevented the increase in
      total lactate production observed after 60 min of hypoxia. However, after 120 min
      of hypoxia, the total lactate production was similar under normoxic and hypoxic
      conditions, and both compounds increased this production. These results indicate
      that glycolysis slowed down between the 60th and 120th minute of hypoxia, while
      EGb and bilobalide delayed the onset of glycolysis activation. In another
      experimental model, both compounds were shown to increase the respiratory control
      ratio of mitochondria isolated from liver of rats treated orally. Since ischemia
      is known to uncouple mitochondria, the protection of ATP content and the delay in
      glycolysis activation observed during hypoxia in the presence of EGb 761 or
      bilobalide is best explained by a protection of mitochondrial respiratory
      activity, at least during the first 60 min of hypoxia incubation. Both products
      retain the ability to form ATP, thereby reducing the cell's need to induce
      glycolysis, probably by preserving ATP regeneration by mitochondria as long as
      oxygen is available.

PMID- 7575686
TI  - Cognitive deficit associated with rheumatic diseases: neuropsychological
      perspectives.

PMID- 7575687
TI  - Characterization of biologically active antineutrophil cytoplasmic antibodies
      induced in mice. Pathogenetic role in experimental vasculitis.
AB  - OBJECTIVE: To investigate the pathogenetic role of antineutrophil cytoplasmic
      antibodies (ANCA) in Wegener's granulomatosis (WG). METHODS: BALB/c mice were
      immunized with human IgG ANCA from a patient with WG. Control mice were immunized
      with normal human IgG. Levels of mouse ANCA and other autoantibodies were
      determined. Mouse ANCA were tested for their ability to induce adhesion and
      respiratory burst of neutrophils. The mouse lungs and kidneys were examined for
      the development of vasculitis. RESULTS: Mice immunized with human ANCA developed
      anti-human ANCA and anti-anti-human ANCA (mouse ANCA), while the controls did not
      develop these antibodies. Mouse ANCA were capable of inducing adhesion of
      neutrophils to fibronectin and activating the respiratory burst in neutrophils.
      Moreover, the mice that were immunized with human ANCA developed perivascular
      mononuclear cell infiltrates in the lungs, suggesting vasculitis. CONCLUSION: The
      results suggest a pathogenic role of ANCA in WG, and may imply that activation of
      neutrophils is the initiating event in the development of vasculitis in WG.

PMID- 7575688
TI  - Monoclonal anticardiolipin autoantibodies established from the (New Zealand white
      x BXSB)F1 mouse model of antiphospholipid syndrome cross-react with oxidized low
      density lipoprotein.
AB  - OBJECTIVE: Autoimmunity-prone (New Zealand white x BXSB)F1 ([NZW x BXSB]F1) mice
      have been shown to be useful as a model of antiphospholipid syndrome with
      myocardial infarction. The aim of this study was to examine the cross-reactivity
      of anticardiolipin antibody (aCL) derived from (NZW x BXSB)F1 mice with oxidized
      low-density lipoprotein (ox-LDL), which is closely associated with
      atherosclerosis. METHODS: Six monoclonal antibodies (MAb) against CL were
      established from (NZW x BXSB)F1 mice, and reactivity of aCL with ox-LDL was
      examined by micro-enzyme-linked immunosorbent assay. RESULTS: Higher titers of
      anti-ox-LDL autoantibodies were found in adult (NZW x BXSB)F1 mice compared with
      other autoimmunity-prone mouse strains (P < 0.01) or a control strain (P <
      0.005). There was a significant positive correlation between titers of aCL and
      those of anti-ox-LDL in (NZW x BXSB)F1 mice (r = 0.79, P < 0.001). Of the 6 MAb
      against CL, 2 clones that showed beta 2-glycoprotein 1-dependent reactivity also
      cross-reacted with ox-LDL. Binding of monoclonal aCL to solid-phase cardiolipin
      was inhibited by ox-LDL, but not by native LDL. CONCLUSION: We confirmed that aCL
      derived from (NZW x BXSB)F1 mice can cross-react with ox-LDL. This result
      suggests that aCL, which is closely associated with lupus-associated thrombosis,
      may also play an important role in atherosclerotic complications in patients with
      systemic lupus erythematosus.

PMID- 7575690
TI  - Use of an antibody against the matrix metalloproteinase-generated aggrecan
      neoepitope FVDIPEN-COOH to assess the effects of stromelysin in a rabbit model of
      cartilage degradation.
AB  - OBJECTIVE: To define the stromelysin cleavage site in the interglobular domain of
      rabbit aggrecan, and to determine whether the stromelysin-generated neoepitope
      can be used as a marker of matrix metalloproteinase (MMP) activity in vivo.
      METHODS: The carboxy-terminus sequence of the stromelysin-generated hyaluronic
      acid-binding region (HABR) of rabbit aggrecan was determined by reverse
      transcription-polymerase chain reaction complementary DNA cloning and DNA
      sequence analysis, followed by purification and mass spectral protein sequence
      analysis of the HABR fragment. Active stromelysin was injected into the stifle
      joints of rabbits, and a stromelysin-generated aggrecan neoepitope was analyzed
      by Western blotting and localized in situ by indirect immunofluorescence.
      Proteoglycan fragments in joint fluids were quantified by a dimethylmethylene
      blue dye-binding assay. RESULTS: Stromelysin cleavage of rabbit aggrecan
      generated a 55-kd HABR fragment that terminated in the sequence FMDIPEN: An anti
      FVDIPEN antibody recognized the FMDIPEN neoepitope in situ in cartilage from
      stromelysin-injected joints. The appearance of the FMDIPEN neoepitope
      corresponded to the release of cartilage proteoglycan fragments into the joint
      fluid, and could be inhibited by pretreatment of the rabbits with a synthetic
      stromelysin inhibitor. CONCLUSION: These results indicate that the anti-FVDIPEN
      antibody can be used to assess the role of MMPs in cartilage degradation in vivo.

PMID- 7575689
TI  - The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase
      involved in transcriptional activation.
AB  - OBJECTIVE: To characterize the complementary DNA (cDNA) and protein sequences of
      autoantigens recognized by anti-Mi-2 antibodies, using recombinant Mi-2 proteins
      for improved autoantibody detection. METHODS: A cDNA expression library was
      immunoscreened, and cDNA isolation, alignment, and sequence analysis were
      performed. Northern blotting and in situ hybridization techniques were used. A
      recombinant protein (rMi-2) was synthesized. Immunoprecipitation of 35S
      methionine-labeled HEp-2 cell proteins and immunoblotting of rMi-2 and natural
      nuclear proteins were performed. Immunofluorescence studies were done with anti
      Mi-2 positive sera of dermatomyositis (DM) patients, and with human or rabbit
      antibodies specific for rMi-2. Antibody screening of systemic lupus
      erythematosus, rheumatoid arthritis, DM, and antinuclear antibody-positive human
      sera was performed using an rMi-2 protein enzyme-linked immunosorbent assay
      (ELISA). RESULTS: A major antigen recognized by anti-Mi-2 positive sera of DM
      patients was found to constitute a 218-kd nuclear protein (218-kd Mi-2) encoded
      on chromosome 12 and to belong to the SNF2/RAD 54 helicase family. Human and
      rabbit antibodies that were affinity purified using the recombinant protein
      reacted with and precipitated a nuclear protein of similar size, which was also
      recognized by anti-Mi-2 sera. Anti-218-kd Mi-2 antibodies detected by rMi-2
      protein ELISA seemed to be mainly restricted to sera from patients with DM.
      CONCLUSION: The molecular characterization of the 218-kd Mi-2 antigen may
      contribute to our understanding of autoimmune phenomena in DM. The use of
      immunoreactive recombinant proteins allows structural and functional studies of
      the helicase and the development of sensitive and accurate antibody screening
      tests.

PMID- 7575691
TI  - Alteration of Chlamydia trachomatis biologic behavior in synovial membranes.
      Suppression of surface antigen production in reactive arthritis and Reiter's
      syndrome.
AB  - OBJECTIVE: To investigate the biologic state of Chlamydia and its surface antigen
      expression in the synovial membranes of patients with Chlamydia-associated
      reactive arthritis/Reiter's syndrome (ReA/RS). METHODS: Expression of chlamydial
      lipopolysaccharide (LPS), major outer membrane protein (MOMP), and elementary
      body (EB) antigens was studied by gold labeling immunoelectron microscopy on 6
      synovial membrane and 2 synovial fluid (SF) pellet samples from 6 patients with
      Chlamydia-associated arthritis. The study findings were compared with 24-hour
      cultures of HeLa cells infected with Chlamydia trachomatis EB. RESULTS:
      Persistent C trachomatis infection was found in all 6 synovial membrane samples
      from patients who had either early or chronic arthritis. The infection persisted
      despite antibiotic treatment, including a 1-month course of doxycycline therapy.
      Most persistent organisms were atypical reticulate bodies (RBs) found in both
      fibroblasts and macrophages. Specific, but weak, immunogold staining for all 3
      antibodies was found on both intracellular RBs and extracellular EBs. In the SF
      samples, Chlamydia surface antigens were detected only in phagosomes containing
      degraded electron-dense materials. CONCLUSION: The synovial membrane biopsies
      conducted in this study of Chlamydia-associated ReA/RS revealed atypical RBs with
      diminished MOMP and LPS expression. Such altered organisms may escape immune
      surveillance and contribute to disease chronicity; moreover, these organisms may
      be difficult to detect and treat in some ReA/RS patients.

PMID- 7575692
TI  - Antibodies to synovial antigens in recent-onset rheumatoid arthritis.
AB  - OBJECTIVE: To identify synovial antigens that bind to serum antibodies from
      subjects with recent-onset rheumatoid arthritis (RA) (< 6 months of synovitis).
      METHODS: Soluble and insoluble fractions of Triton X-100 extracts of RA and
      normal synovial tissue, and normal spleen and placenta, were immunoblotted with
      sera from 27 patients with recent-onset RA, 13 autoimmune disease control
      subjects, and 13 blood bank control donors. Bound immunoglobulin was probed with
      125I-labeled protein A. RESULTS: Antibodies in the sera of 20 (74%) patients with
      recent-onset RA recognized at least 1 of 5 antigens in both a disease- and tissue
      specific and nonspecific manner. Anti-La antibodies, usually associated with
      primary Sjogren's syndrome, were detected in 2 sera. Eight sera had increased
      reactivity to an IgG heavy and light chain dimer. There was strong binding of 8
      sera with a 35-kd doublet and of 3 sera with a 55-kd species in RA and normal
      synovial lysates (insoluble fractions). Two sera uniquely recognized a 45-kd
      protein only in the RA synovial lysate (soluble fraction). CONCLUSION: IgG
      antibodies in the sera of patients with recent-onset RA show positive immunoblots
      for 3 novel synovial antigens of 35-kd, 55-kd, and 45-kd, as well as for 2
      previously characterized antigens (La and IgG). Thus, a variety of synovial
      antigens appear to be recognized by B cells even early in the clinical course of
      RA.

PMID- 7575693
TI  - Translation and validation of arthritis outcome measures into Spanish.
AB  - OBJECTIVE: To produce Spanish versions of common arthritis outcome measures: the
      Health Assessment Questionnaire (HAQ) Disability Scale, the Center for
      Epidemiologic Studies Depression Scale (CES-D), the Medical Outcomes Study (MOS)
      Pain Severity Scale, the Arthritis Self-Efficacy Scale for Pain and Other
      Symptoms (with the addition of 2 new items), the Visual Analogue Pain Scale, the
      MOS Self-Rated Health Item, and a Physical Activities Scale that would be usable
      by most Hispanics living in the US. We tested these translated measures for
      reliability and, where appropriate, validity. METHODS: Instruments were
      translated and back translated by bilingual persons from 5 different countries of
      origin. Translators met to resolve variations in translation. The instruments
      were then administered to Hispanic arthritis patients in 6 geographic locations
      (5 in the United States and 1 in Latin America). All instruments underwent
      standard psychometric testing. As appropriate, the sample was stratified by level
      of acculturation, nation of origin, and geographic location. RESULTS: The
      translated instruments, with slight modification, met acceptable levels of
      reliability and validity. They are understood and easily usable by diverse
      Spanish-speaking populations. CONCLUSION: The availability of these translated
      outcome measures should enable investigators to include monolingual Spanish
      speakers into their studies, and should facilitate study of cross-cultural
      differences with respect to these specific outcomes.

PMID- 7575696
TI  - Prediction of progression of radiologic damage in newly diagnosed rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the extent to which early radiologic damage is
      predicted by joint inflammation in patients with newly diagnosed rheumatoid
      arthritis (RA). METHODS: Regression analysis was performed on 1-year progression
      of total radiologic damage for baseline characteristics and cumulative disease
      activity measures, and the effects of continued joint inflammation on the
      progression of damage in separate joint groups were investigated. RESULTS: Odds
      ratios for progression of total damage were 12 for the presence of rheumatoid
      factor, 5 for the presence of damage at baseline, and 2 for cumulative joint
      inflammation. A positive association between continued joint inflammation and
      progression of damage was found to be statistically significant for most joint
      groups. CONCLUSION: Progression of radiologic damage in patients with newly
      diagnosed RA is independently associated with the presence of rheumatoid factor
      and damage at baseline and with cumulative joint inflammation.

PMID- 7575694
TI  - Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with
      hydroxychloroquine-plus-piroxicam, and piroxicam alone.
AB  - OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein
      (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety
      of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam
      alone, in the treatment of rheumatoid arthritis (RA) patients. METHODS: A double
      blind, randomized, multicenter study in which patients with active RA were
      treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20
      mg/day, or piroxicam alone 20 mg/day, for 24 weeks. RESULTS: At weeks 12 and 24,
      tenidap produced greater improvements than piroxicam based on 5 primary efficacy
      parameters; this improvement showed statistical significance in 4 of the 5
      measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements
      in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with
      piroxicam, tenidap was associated with significantly greater reductions in serum
      CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions
      in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was
      also significantly greater at weeks 4 and 24 in the tenidap-treated group than in
      the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in
      plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group,
      and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The
      overall occurrence of side effects, including gastrointestinal side effects, was
      similar in all 3 treatment groups. A small proportion of tenidap-treated patients
      (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal
      proximal tubular origin, and 3-4% of patients had elevated transaminase levels.
      CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the
      combination of hydroxychloroquine-plus-piroxicam, and is more effective than
      piroxicam alone; moreover, tenidap's safety profile is comparable to that
      observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The
      clinical response observed in this study, as well as the prompt decreases in
      acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest
      that tenidap represents a new type of antiarthritic medication, with properties
      similar to, but not identical to, a therapeutic combination of a nonsteroidal
      antiinflammatory drug with disease-modifying antirheumatic drugs.

PMID- 7575695
TI  - Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment
      in early rheumatoid arthritis.
AB  - OBJECTIVE: To study the effect of chimeric anti-CD4 monoclonal antibody (MAb)
      therapy on synovial inflammation, in order to interpret the clinical experience
      with anti-CD4 treatment. METHODS: The immunohistologic features of synovial
      biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were
      studied in patients with rheumatoid arthritis. The patients received intravenous
      doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1)
      of cM-T412 daily for 5 consecutive days. RESULTS: Although the patients did not
      experience clinical improvement, significant decreases in the number of
      circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the
      mean scores for expression of adhesion molecules were found in the 7 patients 4
      weeks after receiving cM-T412. The scores for infiltration with CD4+ and other
      inflammatory cells were particularly reduced following treatment with either 25
      mg or 50 mg cM-T412. Cytokines, such as interleukin-1 beta and tumor necrosis
      factor alpha, could still be detected in the synovial tissue after treatment.
      CONCLUSION: The decline in the numbers of inflammatory cells and adhesion
      molecules in synovial tissue after CD4+ cell depletion supports the view that
      CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect
      of anti-CD4 therapy might be explained by an insufficient decrease in the number
      of synovial CD4+ cells and by the persistence of cytokines. Determination of
      whether more adequate dosing would lead to a clinical improvement must await
      further study.

PMID- 7575697
TI  - Identification of patient subsets among those presumptively diagnosed with,
      referred, and/or followed up for systemic lupus erythematosus at a large tertiary
      care center.
AB  - OBJECTIVE: To identify different subsets of patients from a large tertiary care
      center who were presumptively referred for and/or diagnosed with systemic lupus
      erythematosus (SLE) (or followed up). METHODS: All patients who were referred,
      followed up, and/or diagnosed with SLE at our center, who had disease duration of
      < or = 5 years, and who resided in Alabama, were identified and their charts
      reviewed and abstracted. RESULTS: Abstracted data were reviewed by 3
      rheumatologists, and patients were assigned to 1 of 3 categories: 1) SLE by the
      American College of Rheumatology (ACR; formerly, the American Rheumatism
      Association) criteria, 2) clinical SLE but not meeting 4 of the ACR criteria, or
      3) fibromyalgia-like manifestations with antinuclear antibody (ANA) positivity.
      There were 90 patients in the first group (criteria), 22 in the second group
      (clinical), and 37 in the third group (fibromyalgia-like). Patients in all 3
      groups were predominantly women. Only 5% of the fibromyalgia-like group were
      African-American, compared with 55-65% for the other 2 groups. Organ system
      involvement occurred with comparable frequency in the first 2 groups, but
      mucocutaneous and hematologic abnormalities were more frequent in the criteria
      group; in contrast, the patients with fibromyalgia-like symptoms primarily
      presented with arthralgias/myalgias, fatigue, depression, and sleep disturbances,
      as well as mucocutaneous manifestations. CONCLUSION: When the ACR criteria for
      SLE are used to determine eligibility for lupus studies, a group of patients with
      clinically unequivocal SLE are excluded. A group of patients with fibromyalgia
      like manifestations, who test positive for ANA and differ clinically and
      sociodemographically from the patients in the other 2 groups, very likely do not
      belong within the spectrum of SLE.

PMID- 7575698
TI  - Presence of nucleosome-restricted antibodies in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To assess whether nucleosome-restricted antibodies, i.e., antibodies
      that react with the whole nucleosome particle but not with its individual
      components (double-stranded DNA [dsDNA] and histones), are present in the sera of
      patients with systemic lupus erythematosus (SLE). METHODS: Antibodies were
      detected by enzyme-linked immunosorbent assay using purified nucleosomes, dsDNA,
      or histones. These tests were applied to the sera of 40 patients with SLE.
      Protein G-purified IgGs of representative sera were sequentially adsorbed on
      dsDNA- and histone-conjugated solid-phase supports and further assayed for their
      nucleosome, dsDNA, and histone reactivities. RESULTS: Of the 40 sera tested, 16
      displayed anti-dsDNA and/or antihistone antibody activity, which was always
      associated with significant antinucleosome reactivity. In addition, 3 sera showed
      antinucleosome activity that was not associated with concomitant anti-dsDNA or
      antihistone activity. The presence of true nucleosome-restricted antibodies was
      demonstrated, after solid-phase adsorption, in representative SLE sera that
      showed anti-dsDNA or antihistone antibody activity, and also in sera that did not
      show these activities. CONCLUSION: Our results provide evidence for the presence
      of nucleosome-restricted antibodies in patients with lupus. These nucleosome
      restricted antibodies, along with anti-dsDNA and antihistone antibodies, appear
      to belong to a broad set of antinuclear antibodies, the antinucleosome family.

PMID- 7575699
TI  - Causes of death in systemic lupus erythematosus. Long-term followup of an
      inception cohort.
AB  - OBJECTIVE: To describe the causes of death in a cohort of patients with systemic
      lupus erythematosus (SLE), and to determine if the major causes of death differ
      according to patient age, sex, race, socioeconomic status, and the duration of
      SLE. METHODS: We examined survival in a cohort of 408 patients with SLE. During a
      median of 11 years of followup, 144 patients died. The cause of death was
      determined for 134 patients (93%). RESULTS: SLE was the most common cause of
      death, occurring in 49 patients (34%), followed by infection (n = 32; 22%),
      cardiovascular disease (n = 23; 16%), cerebrovascular disease (n = 8; 6%), and
      cancer (n = 8; 6%). Deaths due to SLE and due to infections were more common
      among younger patients, and deaths due to cancer were more common among older
      patients. Although the risk of death due to SLE was greatest during the first 3
      years after diagnosis, deaths due to SLE occurred throughout the course of
      disease. CONCLUSION: In this study of patients with SLE who were followed up for
      an extended period of time beginning soon after diagnosis, SLE was the most
      common cause of death, and deaths due to SLE occurred throughout the course of
      illness.

PMID- 7575700
TI  - The incidence and natural history of knee osteoarthritis in the elderly. The
      Framingham Osteoarthritis Study.
AB  - OBJECTIVE: To determine the incidence of radiographic knee osteoarthritis (OA)
      and symptomatic OA (symptoms plus radiographic OA), as well as the rate of
      progression of preexisting radiographic OA in a population-based sample of
      elderly persons. METHODS: Framingham Osteoarthritis Study subjects who had knee
      radiographs and had answered questions about knee symptoms in 1983-1985 were
      reexamined in 1992-1993 (mean 8.1-year interval) using the same protocol.
      Subjects were defined as having new (incident) radiographic OA if they developed
      grade > or = 2 OA (at least definite osteophytes or definite joint space
      narrowing). New symptomatic OA was present if subjects developed a combination of
      knee symptoms and grade > or = 2 OA. Progressive OA was diagnosed when
      radiographs showing grade 2 disease at baseline showed grade > or = 3 disease on
      followup. RESULTS: Of 1,438 participants in the original study, 387 (26.9%) died
      prior to followup. Of the 1,051 surviving subjects, 869 (82.7%) participated in
      the followup study (mean +/- SD age 70.8 +/- 5.0 at baseline). Rates of incident
      disease were 1.7 times higher in women than in men (95% confidence interval [CI]
      1.0-2.7), and progressive disease occurred slightly more often in women (relative
      risk = 1.4; 95% CI 0.8-2.5) but rates did not vary by age in this sample. Among
      women, approximately 2% per year developed incident radiographic disease, 1% per
      year developed symptomatic knee OA, and about 4% per year experienced progressive
      knee OA. CONCLUSION: In elderly persons, the new onset of knee OA is frequent and
      is more common in women than men. However, among the elderly, age may not affect
      new disease occurrence or progression.

PMID- 7575701
TI  - Quantitative bone scintigraphy in the management of monostotic Paget's disease of
      bone.
AB  - OBJECTIVE: To assess the use of quantitative bone scanning (QBS) in the
      monitoring of patients with intravenous pamidronate-treated symptomatic
      monostotic Paget's disease of bone in whom biochemical markers of bone turnover
      are relatively normal. METHODS: QBS was performed in 9 patients and the results
      were expressed as a ratio, obtained by comparing isotope uptake at an affected
      and a control (unaffected) site. RESULTS: Serum alkaline phosphatase levels were
      normal in 7 of the 9 patients and changed minimally with treatment. The median
      QBS ratio was 2.72 (range 1.69-24.6) at baseline and 1.49 (range 0.63-4.18)
      posttreatment (P = 0.008). The median symptom score decreased with treatment, but
      QBS ratios provided the only objective measure of disease activity by which
      response to pamidronate therapy could be judged. CONCLUSION: QBS may be a useful
      technique for evaluating the effects of treatment in patients with Paget's
      disease of bone.

PMID- 7575702
TI  - Lack of detection of enteroviral RNA or bacterial DNA in magnetic resonance
      imaging-directed muscle biopsies from twenty children with active untreated
      juvenile dermatomyositis.
AB  - OBJECTIVE: To investigate for the presence of increased titers of circulating
      antibody to putative infectious agents and for detectable viral RNA or bacterial
      DNA in children with active recent-onset juvenile dermatomyositis (DM). METHODS:
      Magnetic resonance imaging-directed muscle biopsies were performed in 20 children
      with active, untreated, recent-onset juvenile DM and in age-matched children with
      neurologic disease. Sera were tested for complement-fixing antibody to
      Coxsackievirus B (CVB), influenza A and B, parainfluenza 1 and 3, Mycoplasma
      pneumoniae, mumps, respiratory syncytial virus, and Reovirus; and by
      immunofluorescence for IgG antibody to Toxoplasma gondii cytomegalovirus and IgM
      antibody to Epstein-Barr virus. Muscle from juvenile DM patients and control
      children, CD-1 Swiss mice with and without CVB1 infection, and viral stock
      positive for CVB1-6 were tested using reverse-transcriptase polymerase chain
      reaction with 5 primer sets, 4 probes (1 Coxsackievirus, 3 Enterovirus), and
      universal primers for DNA. RESULTS: No increased antibody, viral RNA, or
      bacterial DNA was present in the juvenile DM patients or the control children.
      CONCLUSION: Juvenile DM may be triggered by unidentified agent(s) in the
      genetically susceptible host.

PMID- 7575704
TI  - Clinical image: silicone synovitis.

PMID- 7575703
TI  - Adult respiratory distress syndrome in polymyositis patients with the anti-Jo-1
      antibody.
AB  - We report 3 patients with polymyositis and the anti-Jo-1 antibody who developed
      fatal adult respiratory distress syndrome (ARDS). Other than the presence of the
      anti-Jo-1 antibody, there were no other consistent clinical features at the onset
      of disease that were predictive of ARDS development.

PMID- 7575705
TI  - Ureaplasma urealyticum destructive septic polyarthritis revealing a common
      variable immunodeficiency.

PMID- 7575707
TI  - Diagnosing cytomegalovirus pneumonia: comment on the concise communication by
      Aglas et al.

PMID- 7575706
TI  - Polymerase chain reaction-based genotyping of the constant segment of
      immunoglobulin kappa shows weak or no association with rheumatoid arthritis.

PMID- 7575708
TI  - Possible role of inducible nitric oxide synthase in articular chondrocytes in the
      pathogenesis of arthritic swelling.

PMID- 7575709
TI  - Significance of cytokine measurements in patients with juvenile rheumatoid
      arthritis: comment on the article by Mangge et al.

PMID- 7575710
TI  - Interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid
      arthritis. A double-blind, placebo-controlled trial with open-label extension.
AB  - OBJECTIVE: This pilot phase II, double-blind, placebo-controlled trial of 1 month
      duration, with a 2-3-month open-label extension, evaluated the safety,
      tolerability, biologic effects, and efficacy of interleukin-2 diphtheria fusion
      protein (DAB486IL-2) in refractory rheumatoid arthritis (RA). METHODS: Forty-five
      RA patients were enrolled in the trial, and were randomized, after a 3-4-week
      disease-modifying antirheumatic drug washout, to receive a daily intravenous dose
      of either DAB486IL-2 or placebo (saline) for 5 days. A blinded, third-party
      observer evaluated arthritis activity. Clinical response was defined as > or =
      25% improvement in swollen and tender joints and > or = 25% improvement in at
      least 2 of 6 additional parameters. The double-blind phase was 4 weeks; placebo
      patients could cross over to receive open-label treatment for a maximum of 3
      monthly DAB486IL-2 cycles. RESULTS: In the double-blind phase, 4 of 22 patients
      (18%) in the treated group and none in the placebo group (P = 0.05) met the
      criteria for clinical response. During the open-label treatment phase, 11 of 36
      patients (31%) and 11 of 33 patients (33%) had a clinical response after
      completing 2 and 3 courses of DAB486IL-2, respectively. Adverse events included
      transient fever/chills (45%), nausea/vomiting (50%), elevated (< or = 3 x normal)
      transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo,
      4 DAB486IL-2) did not complete 3 treatment cycles. No apparent differences were
      noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL-2
      treated versus placebo-treated patients. CONCLUSION: Clinical responses were
      noted in patients treated with DAB486IL-2 (18%) compared with placebo (0%) in the
      double-blind phase. In the open-label phase, 33% of patients completing 3 monthly
      DAB486IL-2 cycles had improvement in arthritis activity. Further studies of IL-2
      diphtheria fusion proteins are warranted to elucidate factors that may predict
      clinical response and define mechanism(s) of action.

PMID- 7575711
TI  - Treatment of active refractory rheumatoid arthritis with humanized monoclonal
      antibody CAMPATH-1H administered by daily subcutaneous injection.
AB  - OBJECTIVE: To investigate the dose tolerance and potential clinical activity of a
      humanized antilymphocyte monoclonal antibody, CAMPATH-1H (C1H), in patients with
      active, refractory rheumatoid arthritis (RA). METHODS: Thirty adult patients with
      active, refractory RA were treated in an open-label, 3-center, dose-escalation
      study of subcutaneously injected C1H. Six patients were assigned to each of 5
      dosage groups (0.3, 1.0, 3.0, 10.0 or 30.0 mg/day), and received 10 daily
      injections of C1H over a 12-day period. RESULTS: Side effects occurred primarily
      during the first 1-2 days of dosing, and included mild fever, chills, nausea,
      vomiting, headache, and, in a minority of patients, hypotension. All patients
      developed some discomfort at the injection site. Self-limited infections occurred
      in 5 patients during the 6-month study period. Peripheral blood lymphocyte counts
      fell promptly after initial dosing and recovered slowly, usually over 2-3 months.
      Serum antibodies to C1H developed in 54% of patients following treatment.
      Clinical improvement was observed in 56% of patients, based on the composite
      Paulus criteria, with a median time-to-response of 22 days and a median response
      duration of 32 days. CONCLUSION: C1H is a lymphocyte-depleting antibody that
      exhibits biologic potency when administered subcutaneously to patients with
      refractory RA. Its use is associated with mild to moderate toxicity and short
      term amelioration of disease activity.

PMID- 7575712
TI  - Light and electron microscopic analysis of sequential liver biopsy samples from
      rheumatoid arthritis patients receiving long-term methotrexate therapy. Followup
      over long treatment intervals and correlation with clinical and laboratory
      variables.
AB  - OBJECTIVE: To describe liver histopathologic features and ultrastructural changes
      in a prospectively studied cohort of rheumatoid arthritis (RA) patients receiving
      long-term methotrexate (MTX) therapy, and to seek correlations between these
      changes and simultaneously measured laboratory indices of liver function.
      METHODS: This was a long-term, prospective, open observational study. Twenty
      seven outpatients with RA who began therapy with MTX and continued treatment for
      extended periods underwent baseline and followup liver biopsies. One hundred
      seventy liver biopsy specimens were analyzed by light microscopy (LM) and
      assessed according to a modified Roenigk score and a newly devised numerical
      grading system. Ninety-three biopsy specimens were also analyzed by electron
      microscopy (EM). Blood samples were obtained at 4-6-week intervals for
      determination of bilirubin, alkaline phosphatase, aspartate aminotransferase
      (AST), and albumin levels, and the weekly dosage of MTX was adjusted if there
      were abnormalities in the AST or albumin level. A mean of 6.3 liver biopsies per
      patient were obtained over a mean followup period of 8.2 years (range 2-13
      years). RESULTS: The modified Roenigk score was significantly different from
      baseline at year 3, when it increased from a mean of 1.8 to 2.3 (P = 0.05) and at
      year 6, when it increased to 2.4 (P = 0.04), but this was not considered
      clinically meaningful. No other significant changes from baseline were observed
      by either LM grading system. No significant progression was observed by EM over
      the course of the investigation. Increases in serial measurements of AST
      correlated with both the modified Roenigk score (r = 0.21, P = 0.016) and the
      numerical rating score (r = 0.19, P = 0.027). CONCLUSION: Patients with RA who
      are receiving weekly single-dose oral MTX therapy exhibit little deterioration in
      hepatic architecture by LM or EM when the dosage of the drug is adjusted for
      abnormalities in AST and serum albumin, monitored at frequent intervals.

PMID- 7575713
TI  - Longitudinal study of hand bone densitometry in rheumatoid arthritis.
AB  - OBJECTIVE: To measure hand bone mineral content (BMC) by dual x-ray
      absorptiometry and to seek clinical correlates in patients with rheumatoid
      arthritis (RA), in a prospective, longitudinal study. METHODS: Eighty-one
      patients with non-steroid-treated RA were assessed at baseline and at month 12,
      for hand BMC and for disease activity and severity. Hand BMC in patients was
      compared with that in a control group of 95 normal volunteers, and rate of loss
      was compared with that in 37 controls. RESULTS: At the initial assessment, male
      and female patients with RA had lower hand BMC than controls, after correction
      for age, height, and weight (mean reduction 7.5% in men [P = 0.003] and 7.8% in
      women [P = 0.01]). After 1 year, there was a further loss of hand BMC in patients
      (median loss 3.25% in men [P = 0.001] and 1.46% in women [P = 0.05]), but normal
      controls did not have significant changes in their hand BMC. In patients with
      disease duration of < 2 years at study entry, the parameters of disease activity
      improved over 1 year, but they lost significant amounts of hand BMC. Hand BMC
      loss correlated with baseline C-reactive protein levels. In those with RA of > 2
      years duration at entry, the Health Assessment Questionnaire scores and Larsen
      scores had worsened after 1 year, but there was no significant loss of hand BMC.
      CONCLUSION: Patients with RA had low hand BMC compared with normal controls, even
      within 2 years of disease onset. The rate of loss was highest in patients with
      early disease and correlated with measures of initial disease activity. This loss
      continued despite clinical improvement.

PMID- 7575714
TI  - Sleep electroencephalography and the clinical response to amitriptyline in
      patients with fibromyalgia.
AB  - OBJECTIVE: To determine the prevalence and clinical correlations of an anomaly
      consisting of electroencephalographic (EEG) waves within the alpha frequency band
      during non-rapid eye movement (NREM) sleep in patients with fibromyalgia, and to
      evaluate the alpha NREM sleep anomaly as a predictor of response to
      amitriptyline. METHODS: Twenty-two patients with fibromyalgia were studied in a 2
      month, double-blind, crossover trial of amitriptyline (25 mg/day) versus placebo.
      Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end
      of each 2-month treatment period. RESULTS: Six patients (27%) had a clinical
      response to amitriptyline, while none responded to placebo (P = 0.02). Treatment
      with amitriptyline or placebo did not result in any changes in the alpha ratings
      during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly
      at baseline. Those patients reported more sleep difficulty, but otherwise were
      clinically indistinguishable from those without this EEG sleep anomaly. Lower
      baseline alpha NREM sleep ratings were seen in responders to amitriptyline than
      in nonresponders, but these differences did not reach statistical significance.
      CONCLUSION: The alpha NREM sleep anomaly is present in only a small proportion of
      patients with fibromyalgia. It does not correlate with disease severity nor is it
      affected by treatment with amitriptyline. A larger sample size will be needed to
      adequately assess the value of this sleep anomaly in predicting the response to
      amitriptyline.

PMID- 7575715
TI  - A longitudinal study of functional disability in a national cohort of patients
      with polymyositis/dermatomyositis.
AB  - OBJECTIVE: To analyze changes in functional status and the factors contributing
      to disability in a national inception cohort of 257 patients with
      polymyositis/dermatomyositis (PM/DM). METHODS: Data were gathered from patients'
      self-reports on questionnaires: one concerning disease- and treatment-related
      complications, and the other concerning disability, as reflected by a disability
      index (DI) derived from the Health Assessment Questionnaire (HAQ). RESULTS: Based
      on certain characteristics that differentiated disability patterns, 3 groups of
      patients were identified. Group 1 patients (n = 153) were < or = 60 years old and
      never had avascular necrosis (AVN) or a vertebral compression fracture (CF),
      Group 2 patients were > 60 and never had AVN or a vertebral CF, and Group 3
      patients reported AVN or a vertebral CF irrespective of age. As measured by the
      HAQ DI, disability increased very gradually over time in Group 1 patients and
      more rapidly in Group 2 and Group 3 patients. The increase in disability in
      patients experiencing AVN was greater than that in patients with similar pre-AVN
      disease characteristics who did not develop AVN (P = 0.003). CONCLUSION: In this
      prospective study of disease course and iatrogenic factors related to functional
      disability in PM/DM, the HAQ DI increased with disease duration. Corticosteroid
      related morbidity, as reflected by the development of AVN or CF, significantly
      contributed to patient-reported functional disability.

PMID- 7575716
TI  - Nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children.
AB  - OBJECTIVE: To determine the incidence of abdominal pain and gastroduodenal injury
      in children with arthritis taking nonsteroidal antiinflammatory drugs (NSAIDs).
      METHODS: A retrospective review of the records of all children (570 patients)
      receiving followup care in an academic rheumatology clinic between 1991 and 1993
      was performed. RESULTS: There were 344 patients who used NSAIDs during the study
      period. Abdominal pain was recorded in 27.9% of patients taking NSAIDs and 14.6%
      of patients not taking NSAIDs. Abdominal pain in 47 patients (49%) taking NSAIDs
      and 14 patients (42%) not taking NSAIDs was evaluated radiographically and/or
      endoscopically. Among those patients evaluated, gastric or duodenal injury was
      found in 16 (34.0%) who were taking NSAIDs and 1 (7.1%) who were not. This
      represented a relative risk for gastroduodenal injury of 4.8 for patients taking
      NSAIDs (P = 0.09). The incidence of injury did not change when analyses were
      controlled for prednisone or slow-acting antirheumatic drug use. None of the
      children were hospitalized or died as a result of gastroduodenal injury during
      the 3-year period. CONCLUSION: We conclude that NSAID use in children with
      arthritis frequently leads to gastroduodenal injury, with an estimated incidence
      and relative risk that are comparable to the rates found in adults with arthritis
      taking NSAIDs, but that hospitalization or death as a result of this injury is
      uncommon.

PMID- 7575717
TI  - Number of children as a risk factor for low back pain in men and women.
AB  - OBJECTIVE: To estimate the influence of the number of liveborn children on the
      risk of low back pain. METHODS: The study design was a cross-sectional population
      based survey. The 4,501 respondents to a postal survey were asked to provide data
      on the occurrence of low back pain and on any children they had. Data on some
      potential confounding variables were also obtained. RESULTS: There was an
      increased risk of low back pain in those who were married compared with those who
      were unmarried, among both men (odds ratio 1.7) and women (odds ratio 1.6). Among
      married individuals, there was a linear trend of increasing risk with increasing
      numbers of children. CONCLUSION: The risk of low back pain is related more to
      childrearing than to childbearing, although this effect might be partially
      mediated by unknown confounders associated with increasing family size.

PMID- 7575718
TI  - Degenerative lumbar spinal stenosis. Diagnostic value of the history and physical
      examination.
AB  - OBJECTIVE: To assess the value of the history and physical examination findings
      in the diagnosis of symptomatic degenerative lumbar spinal stenosis (LSS).
      METHODS: The study was performed in 3 specialty clinics, and included patients
      with low back pain who were at least age 40. Findings from a standardized history
      and physical examination were compared with the diagnostic impression of expert
      attending clinicians. Imaging studies were available in 88% of those with LSS,
      and the findings further supported the diagnosis of LSS in each case. The
      sensitivity, specificity, and likelihood ratio associated with each history and
      physical examination finding were calculated in bivariate analyses, and
      independent correlates of LSS were identified with multivariate analyses.
      RESULTS: Ninety-three patients were evaluated. History findings most strongly
      associated with the diagnosis of LSS (likelihood ratio > or = 2) were greater
      age, severe lower-extremity pain, and absence of pain when seated. Physical
      examination findings most strongly associated with the diagnosis were wide-based
      gait, abnormal Romberg test result, thigh pain following 30 seconds of lumbar
      extension, and neuromuscular deficits. Independent correlates of LSS included
      advanced age (P = 0.0001), absence of pain when seated (P = 0.006), wide-based
      gait (P = 0.013), and thigh pain following 30 seconds of lumbar extension (P =
      0.002). CONCLUSION: Specific history and physical examination findings are useful
      in the diagnosis of LSS and should be ascertained routinely in older patients
      with low back pain.

PMID- 7575719
TI  - Emergence of oligoclonal T cell populations following therapeutic T cell
      depletion in rheumatoid arthritis.
AB  - OBJECTIVE: To examine the compartment of CD4+ T cells in patients with rheumatoid
      arthritis (RA) who have developed persistent lymphopenia following antibody
      mediated T cell depletion and to investigate why T cell depletion is of limited
      therapeutic efficacy. METHODS: Circulating T lymphocytes from 10 patients with
      seropositive RA treated with the monoclonal antibody (MAb) CAMPATH-1H were
      longitudinally monitored by fluorescence-activated cell sorter analysis with MAb.
      To assess the molecular diversity of repopulating T cells, random samples of T
      cell clones from the peripheral blood of 3 patients were analyzed by sequencing
      the T cell receptor (TCR) beta chains. At the time of recurring disease, the
      synovial tissue was examined by immunohistochemistry, and the repertoires of
      peripheral and synovial tissue T cells were compared by TCR beta-chain sequencing
      and by semiquantitative hybridization with oligonucleotides specific for the V-D
      J beta junctional region of selected clones. RESULTS: The reconstitution of the
      peripheral T cell compartment was very slow. A mean CD4+ T cell count of
      105/microliters was reached 34 weeks following MAb treatment. After treatment,
      the percentage of CD4+ T cells with the CD45RO+ phenotype was significantly
      increased (P = 0.001), indicating the expansion of antigen-primed memory T cells.
      TCR beta-chain sequences revealed a marked restriction in the diversity of
      repopulating T cells with the emergence of dominant clonotypes. Despite the low
      counts of peripheral CD4+ T cells, the synovial tissue was infiltrated by CD4+ T
      cells to a similar extent as that in RA patients not treated with MAb. Selected
      clonotypes that had emerged in the peripheral blood compartment dominated the
      repertoire of tissue-infiltrating T cells in the synovium. CONCLUSION: In
      patients with RA, T cell depletion induces a long-term imbalance in T cell
      homeostasis. Clonal proliferation of CD4+ T cells severely restricts the
      diversity of available T cell specificities and results in the emergence of
      dominant clonotypes, which accumulate in the synovial tissue despite peripheral
      lymphopenia.

PMID- 7575720
TI  - Hematologic and cytofluorographic analysis of patients with Felty's syndrome. A
      hypothesis that a discrete event leads to large granular lymphocyte expansions in
      this condition.
AB  - OBJECTIVE: To compare hematologic and cytofluorographic features in Felty's
      syndrome (FS) patients with and without the large granular lymphocyte (LGL)
      syndrome. METHODS: Peripheral blood cells from FS patients and from 2 control
      groups (rheumatoid arthritis [RA] patients and subjects without symptoms of a
      rheumatic disease) were analyzed by hematologic and cytofluorographic techniques.
      A separate assessment of disease activity was performed. RESULTS: FS patients had
      reduced lymphocyte and platelet counts, with a parallel reduction in lymphocyte
      subsets examined. CD4 counts were reduced in all FS patients, including those
      with the LGL syndrome. Disease activity was lower in FS patients than in RA
      control patients. Treatment was similar in all patient groups. No direct
      association was seen between LGL numbers and duration of RA or neutrophil counts
      in RA groups. CONCLUSION: Hematologic abnormalities in FS extend beyond
      neutropenia. Although similarities were seen between FS patients and FS patients
      with the LGL syndrome (e.g., CD4 lymphopenia), evidence for a gradation from FS
      to the LGL syndrome was not seen, thus favoring the hypothesis that a
      "transforming event" is required.

PMID- 7575721
TI  - Incidence of systemic lupus erythematosus. Race and gender differences.
AB  - OBJECTIVE: To examine racial differences in the incidence of systemic lupus
      erythematosus (SLE). METHODS: A population-based registry of SLE patients in
      Allegheny County, Pennsylvania, was used to identify incident cases of SLE
      diagnosed between January 1, 1985 and December 31, 1990, from 3 sources, by
      medical record review (University of Pittsburgh Lupus Databank, rheumatologists,
      and hospitals). Capture-recapture methods using log-linear models were used to
      estimate the level of case-finding and to calculate 95% confidence intervals
      (CI). Incidence rates were calculated per 100,000 population. RESULTS: A total of
      191 definite and 78 probable incident cases of SLE were identified, and the
      overall annual incidence rates were 2.4 (95% CI 2.1-2.8) and 1.0 (95% CI 0.8
      1.3), respectively. The crude incidence rates of definite SLE were 0.4 for white
      males, 3.5 for white females, 0.7 for African-American males, and 9.2 for African
      American females. The annual incidence rates of definite SLE remained fairly
      constant over the study interval. African-American females with definite SLE had
      a younger mean age at diagnosis compared with white females (P < 0.05). Since the
      overall ascertainment rate was high (85%; 95% CI 78-92%), the ascertainment
      corrected incidence rate for definite SLE, 2.8 (95% CI 2.6-3.2), was similar to
      the crude rate. CONCLUSION: Our rates clearly confirm previous reports of an
      excess incidence of SLE among females compared with males and among African
      Americans compared with whites. We have used capture-recapture methods to improve
      the accuracy of SLE incidence rates, and we advocate their use to facilitate
      comparisons across studies.

PMID- 7575722
TI  - Heterogeneity in the expression of Ro and La antigens in human skin.
AB  - OBJECTIVE: To determine whether there are variations in the expression of Ro and
      La antigens in human skin. METHODS: Levels of expression of Ro and/or La antigens
      in 26 specimens of normal human skin (11 sun-exposed, 15 sun-protected) were
      measured by indirect immunofluorescence with monospecific antisera. RESULTS:
      Levels of expression of both antigens varied by more than 2,000-fold in the skin
      of different individuals. There usually was a correlation between the levels of
      expression of Ro and La antigens in the same skin specimen. There was no
      correlation found between the levels of Ro or La antigen expression and sun
      exposure, nor was there a correlation found between levels of antigen expression
      and location of the skin on the body. CONCLUSION: There is a marked heterogeneity
      in the expression of both Ro and La antigens in the skin of different
      individuals. The present study findings suggest that the levels of expression of
      these antigens may play a role in the propensity of some individuals to develop
      anti-Ro or anti-La antibodies and/or skin lesions associated with the presence of
      these antibodies.

PMID- 7575723
TI  - Klebsiella pneumoniae-reactive T cells in blood and synovial fluid of patients
      with ankylosing spondylitis. Comparison with HLA-B27+ healthy control subjects in
      a limiting dilution study and determination of the specificity of synovial fluid
      T cell clones.
AB  - OBJECTIVE: To study the frequency of Klebsiella pneumoniae-responsive T cells in
      the peripheral blood (PB) of ankylosing spondylitis (AS) patients compared with
      that in healthy HLA-B27+ donors, and to examine T lymphocyte clones (TLC) derived
      from AS patient synovial fluid (SF) for the presence of Klebsiella reactivity.
      METHODS: Limiting dilution analysis of PB T cells in 8 patients with active AS
      and in 8 HLA-B27+ healthy subjects was used to determine the frequency of PB T
      cells responsive to K pneumoniae and Escherichia coli GroEL. SF T cells from a
      patient with active AS were cloned, and 125 TLC were characterized in
      proliferation assays. RESULTS: There were fewer T cells in the PB of AS patients
      that reacted with K pneumoniae than in the PB of healthy HLA-B27+ subjects. The
      frequencies of E coli GroEL-responsive T cells were approximately 5-10 times
      lower in all subjects tested (healthy donors and AS patients), but without
      significant differences between the 2 groups. Two CD4+ TLC that recognized K
      pneumoniae (1 cross-reactive with E coli) as well as 3 TLC that recognized GroEL
      (2 CD4+, 1 T cell receptor gamma/delta+) were isolated from the SF of a patient
      with actige AS. CONCLUSION: Our results indicate that there is a quantitative
      reduction of K pneumoniae-responsive T cells in the PB of AS patients as compared
      with healthy controls. This may reflect a defective peripheral T cell defense in
      the immune response to Klebsiella and may allow bacterial antigens to reach the
      synovium, where they initiate specific T cell responses.

PMID- 7575724
TI  - Characterization of the binding region for the Yersinia enterocolitica adhesin
      YadA on types I and II collagen.
AB  - OBJECTIVE: The plasmid-encoded adhesin YadA confers pathogenic functions on
      Yersinia enterocolitica, a microorganism associated with reactive arthritis.
      While emerging evidence has indicated that the persistence of the bacteria in
      individuals with reactive arthritis is a prerequisite for the development of the
      disease, the tissue specificity of this immunologic disease sequela remains
      elusive. The present study was undertaken to investigate YadA-mediated binding of
      Y enterocolitica to the most abundant collagens in joints, types I and II
      collagen. METHODS: Binding studies were performed with recombinant Y
      enterocolitica strains and highly purified type II collagen and the alpha 1(I)
      chain of type I collagen, or fragments of these collagens generated by various
      enzymatic and nonenzymatic cleavage procedures. Interactions of bacteria with the
      proteins were determined in binding assays with radiolabeled proteins. RESULTS:
      Binding regions for YadA were identified at the 181-amino acid fragment alpha
      1(I)78CBN of type I collagen and the CB10 fragment of type II collagen. From
      binding and blocking experiments with alpha 1(I) fragments, cyanogen bromide
      derived or mammalian collagenase-derived type II collagen fragments, and
      synthetic peptides with collagen-like structures, it was concluded that the
      binding site for YadA on collagen is determined by a restricted amino acid
      sequence and is defined within a highly homologous 134-amino acid region.
      Furthermore, the binding site is not affected by mammalian collagenase digest.
      Binding of YadA-positive yersiniae to collagen could be inhibited by an antiserum
      specific for YadA. CONCLUSION: This study provides the first evidence of a
      binding site for bacterial proteins on collagens which is not determined by the
      repetitive sequence Gly-X-Y of collagens. We speculate that the binding region is
      conserved between types I and II collagen, the most abundant collagens in the
      joints. Specific binding of Yersinia products to joint collagens might contribute
      to the arthritogenic potential of enteropathogenic yersiniae.

PMID- 7575725
TI  - Effects of tenidap on canine experimental osteoarthritis. I. Morphologic and
      metalloprotease analysis.
AB  - OBJECTIVE: To examine the effects of tenidap and diclofenac on osteoarthritic
      lesions and metalloprotease activity in experimental osteoarthritis (OA).
      METHODS: The anterior cruciate ligament of the right stifle joint of 25 mongrel
      dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were
      treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac
      (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap
      (3 mg/kg/twice daily) plus omeprazole (20 mg/day). The dogs received medication
      for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs
      were used as controls. Lesions were evaluated macroscopically for the incidence
      and size of osteophytes and the area and grade of cartilage erosions on the
      condyles and plateaus, along with histologic evaluation of the severity of the
      cartilage lesions and synovial inflammation. Stromelysin and collagenase
      activities and the collagenase messenger RNA (mRNA) level were measured in
      cartilage and synovial membrane. RESULTS: Compared with the untreated or
      omeprazole-treated OA groups, the dogs treated with tenidap exhibited significant
      reduction in the incidence (P < or = 0.001) and size (P < or = 0.0001) of
      osteophytes. Tenidap also significantly decreased the size and grade of cartilage
      macroscopic lesions, as well as the histologic severity of cartilage lesions on
      both condyles and plateaus. The histologic severity of synovial inflammatory
      reaction was also significantly reduced (P < or = 0.003) in the tenidap group.
      Tenidap markedly decreased stromelysin and collagenase activity in both cartilage
      (stromelysin P < or = 0.003; collagenase P < or = 0.01) and synovial membrane
      (stromelysin P < or = 0.003; collagenase P < or = 0.005). Moreover, tenidap also
      decreased the collagenase mRNA level in cartilage (P < or = 0.005) and synovial
      membrane (P < or = 0.002). Diclofenac slightly reduced the incidence and size of
      osteophytes and cartilage lesions, but these changes were not statistically
      significant. Diclofenac had no effect on the severity of synovial inflammation,
      metalloprotease activity, or collagenase expression. CONCLUSION: This study
      showed that tenidap had a more potent anti-osteoarthritic effect than diclofenac
      in this model. The effect of the drug in suppressing metalloprotease synthesis, a
      process known to play a major role in the pathophysiology of osteoarthritic
      lesions, may explain its mechanism of action.

PMID- 7575726
TI  - Signal transduction through chondrocyte integrin receptors induces matrix
      metalloproteinase synthesis and synergizes with interleukin-1.
AB  - OBJECTIVE: To study the role of signal transduction via integrin receptors in the
      production of metalloproteinase by rabbit articular chondrocytes. METHODS:
      Confluent, primary rabbit articular chondrocytes (RAC) were incubated for 72
      hours in the presence of interleukin-1 (IL-1), Arg-Gly-Asp (RGD) peptide, or a
      combination of IL-1 and RGD peptide. Media were analyzed for stromelysin
      enzymatic activity using a 3H-labeled transferrin substrate, and for stromelysin
      and collagenase protein by Western analysis. Gelatinase activity was analyzed by
      gelatin zymography. IL-1 receptor antagonist (IL-1Ra) protein was used to
      determine the involvement of IL-1 in mediating the effects of RGD peptide, and
      fluorescence-activated cell sorter analysis (FACS) was used to examine the effect
      of IL-1 on chondrocyte integrin subunit expression. RESULTS: RGD peptides induced
      chondrocyte synthesis of stromelysin, collagenase, and 92-kd gelatinase B, and
      increased synthesis of the constitutively expressed 72-kd gelatinase A. Further
      studies focusing on stromelysin demonstrated that this up-regulation was
      concentration dependent and that RGD peptides synergized with IL-1 in inducing
      stromelysin synthesis. RGD-induced stromelysin production was inhibited by the IL
      1Ra in a concentration-dependent manner, indicating that induction by RGD
      requires binding of IL-1 to its receptor. FACS analysis of RAC showed that IL-1
      stimulation increased the expression of beta 1 and alpha v integrin subunits on
      the chondrocyte surface. CONCLUSION: Our data demonstrate that signal
      transduction through chondrocyte integrin receptors up-regulates
      metalloproteinase expression and that this is likely mediated through induction
      of IL-1. They also suggest that the binding of adhesion molecules to their
      chondrocyte integrin receptors reduces the amount of IL-1 required to induce
      stromelysin synthesis. Up-regulation of chondrocyte integrin expression by IL-1
      may play a role in the synergistic effects seen with a combination of IL-1 and
      RGD peptides. Since elevated levels of both IL-1 and adhesion molecules are
      present in rheumatoid arthritis and osteoarthritis synovial fluid, our data
      suggest that this interaction may be important in mediating the cartilage
      destruction accompanying these diseases.

PMID- 7575728
TI  - Tuberculous and foreign-body granulomatous reactions involving a total knee
      prosthesis.
AB  - This case report describes loosening of a right knee prosthesis and represents
      the first report of the simultaneous occurrence of 2 granulomatous processes
      involving a prosthetic joint. Microscopic examination of the tissue revealed
      areas of foreign-body granulomas and areas of necrotizing granulomas and
      caseation. Acid-fast bacilli cultures were positive for Mycobacterium
      tuberculosis. The pathophysiology of implant loosening following an inflammatory
      reaction to components of prosthetic materials is discussed. Also discussed is
      the occurrence of infectious complications and rarity of tuberculous infections
      associated with prosthetic implants.

PMID- 7575729
TI  - Progressive joint destruction in a human immunodeficiency virus-infected patient
      with rheumatoid arthritis.
AB  - This article reports the case of a 63-year-old patient with rheumatoid arthritis
      (RA) whose symptoms of RA improved after the occurrence of a secondary human
      immunodeficiency virus (HIV) infection; however, the HIV infection did not affect
      the histologic parameters of joint destruction to the same extent as it did the
      clinical symptoms. Histologic and immunohistologic joint examinations of this
      patient revealed an ongoing production of cartilage- and bone-degrading enzymes
      by macrophages and fibroblasts, without the presence of T cells. These findings
      demonstrate that progressive joint destruction in RA can occur in the absence of
      T cells. Moreover, our results support the hypothesis that both T cell-dependent
      and T cell-independent pathways play a significant role in the pathogenesis of
      RA.

PMID- 7575727
TI  - Loosening of a revision total hip replacement in a 60-year-old woman with
      longstanding rheumatoid arthritis.

PMID- 7575730
TI  - Glomerulonephritis associated with complete deficiency of the fourth component of
      complement. Response to intravenous immunoglobulin.
AB  - A 15-year-old girl with complete C4 deficiency and a lupus-like disorder
      developed evidence of nephritis after 4 years of followup. Renal biopsy
      demonstrated an immune complex glomerulonephritis, with deposits in the capillary
      loops, the paramesangium, and the mesangial matrix. Renal function was normal.
      The patient was treated with monthly infusions of intravenous immunoglobulin for
      6 months. The treatment was well tolerated, and resulted in resolution of the
      rash and hematuria. Followup biopsy showed less proliferation and fewer loop
      deposits. In light of the serious risk of infections that is associated with
      complement deficiency, approaches to glomerulonephritis that do not include
      immunosuppression should be considered.

PMID- 7575731
TI  - Hydatid disease. An unusual cause of chronic monarthritis.
AB  - We describe a patient with granulomatous synovitis secondary to osseus hydatid
      disease that manifested with chronic monarthritis, eosinophilia, and urticaria.

PMID- 7575732
TI  - Association of HLA-DR5 (possibly DRB1*1201) with the primary antiphospholipid
      syndrome in Mexican patients.

PMID- 7575733
TI  - Cytarabine therapy for refractory cutaneous lupus.

PMID- 7575735
TI  - Severity of rheumatoid arthritis in Greek versus English patients: comment on the
      article by Drosos et al.

PMID- 7575734
TI  - Clomiphene therapy and its potential role in rheumatic symptoms: comment on the
      article by A. and E. Ben-Chetrit.

PMID- 7575736
TI  - Treatment of scleroderma lung disease: comment on the article by Steen et al.

PMID- 7575737
TI  - Diffuse idiopathic skeletal hyperostosis: comment on the clinical image by Kraus
      and Valencia.

PMID- 7575738
TI  - Expression of activation markers of the rheumatoid arthritis synovial membrane:
      comment on the article by Qu et al.

PMID- 7575739
TI  - Methotrexate as a steroid-sparing agent in Cogan's syndrome: comment on the
      concise communication by Richardson.

PMID- 7575740
TI  - Possible role of bone marrow fat in the development of an inflammatory response
      to sickled erythrocytes: comment on the article by Mann and Schumacher.

PMID- 7575741
TI  - Effects 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 on the responses of isolated canine
      arteries.
AB  - The effects of NKY-722 ((+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl
      1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
      dihydrochloride, CAS 117241-46-0), a new water soluble dihydropyridine derivative
      on the responses of isolated canine arteries were examined. NKY-722 (IC50: 5-16 x
      10(-10) mol/l), nicardipine (IC50: 5-10 x 10(-10) mol/l) and nifedipine (IC50: 44
      195 x 10(-10) mol/l) relaxed four arteries in the potency order of basilar >
      coronary > mesenteric > intrarenal arteries. NKY-722 was nearly equipotent to
      nicardipine and about 10 times more potent than nifedipine. [3H]NKY-722 was
      accumulated in the four arteries in the same order of amount as the
      vasoinhibitory effect. All three drugs inhibited the contraction induced by Ca2+
      and methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylophenyl)-p yri
      dine-5- carboxylate (Bay K 8644) in the mesenteric arteries, indicating their
      Ca2+ antagonistic actions. NKY-722 and nicardipine were nearly equipotent and
      about 100 times more potent than nifedipine on the Ca(2+)-induced contraction and
      was about 4 times more potent than nicardipine and 400 times more potent than
      nifedipine on the Bay K 8644-induced contraction. NKY-722, nicardipine and
      nifedipine relaxed the mesenteric arteries precontracted with KCl by more than
      90%, while they relaxed the arteries contracted with PGF2 alpha, 9,11-dideoxy-9
      alpha, 11 alpha-methanoepoxy-PGF2 alpha (U-46619) and endothelin-1 only by 40
      70%. The IC50 values of NKY-722 and nicardipine were similar and much smaller
      than that of nifedipine for all four contracting agents.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7575742
TI  - Morphological aspects of the effects of orotic acid and magnesium orotate on
      hypercholesterolaemia in rabbits.
AB  - Heart and blood vessel diseases are one of the leading causes of death, so their
      prevention and therapy are very important. In the present study the effects of
      magnesium chloride, magnesium orotate and orotic acid were tested. New Zealand
      rabbits were fed with enriched (2%) cholesterol diet during 112 days; starting
      with day 56 all rabbits were treated with MgCl2, Mg-orotate or orotic acid
      (orally). Aortas, coronaries, renal and femoral arteries were removed and
      evaluated by morphological and morphometric methods. Atherosclerotic alterations
      in each vessel could be influenced moderately by Mg-chloride, quite well by
      orotic acid and excellently by Mg-orotate. From these results one can conclude
      that orotic acid and Mg-orotate have a beneficial effect in the prevention and
      therapy of heart and vessels diseases.

PMID- 7575743
TI  - Myocardial effects of flavonoids from Crataegus species.
AB  - The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae)
      on coronary flow, heart rate and left ventricular pressure as well as on the
      velocity of contraction and relaxation was investigated in Langendorff perfused
      isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was
      evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of
      coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside
      (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive
      lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%)
      were the major effects observed at a maximum concentration of 0.5 mmol/l.
      Furthermore, slight positive inotropic effects and a rise in heart rate were
      seen. Similar but less intensive actions were found with the C-glycosides
      vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta
      adrenergic activities of the flavonoids could be excluded by the addition of
      propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover,
      pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial
      activity of hyperoside (10(-4) mol/l). As previous experiments showed an
      inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the
      results suggest an inhibition of this enzyme as the possible underlying mechanism
      of cardiac action of flavonoids from Crataegus species.

PMID- 7575744
TI  - Inhibition of carbonic anhydrase by nitric oxide.
AB  - The aim of the present study was to follow the effect of nitric oxide (NO) on
      carbonic anhydrase in vitro and in vivo. The effect of L-arginine (as source of
      NO), as well as that of its analogue, nitro-G-monomethyl-L-arginine, an inhibitor
      of NO synthesis on carbonic anhydrase, were also studied. In vitro results showed
      that L-arginine activates carbonic anhydrase, while N-G-monomethyl-L-arginine
      does not modify its activity. In vivo, L-arginine and N-G-monomethyl-L-arginine
      increased carbonic anhydrase activity by 72% and, 160% respectively.
      Administration of L-arginine, as a source of NO, and of acetazolamide before
      administration of N-G-monomethyl-L-arginine abolished the activating effect of
      the analogue on carbonic anhydrase. These results lead to the conclusion that
      inhibition of NO synthesis by N-G-monomethyl-L-arginine induces increase of
      carbonic anhydrase activity. The data also suggest that NO biosynthetized from L
      arginine inhibits carbonic anhydrase.

PMID- 7575745
TI  - [Testing of bioequivalence of a new sotalol hydrochloride preparation in
      comparison to a standard formulation].
AB  - An investigation on the bioavailability of a new tablet with 160 mg sotalol
      hydrochloride (CAS 959-24-0, Rentibloc 160), was performed in a two-way cross
      over study with 16 volunteers. The relative bioavailability with respect to a
      reference preparation for AUC0-infinity was 98.1% and for Cmax 100.8%. A positive
      decision for bioequivalence derived from the usual confidence intervals for both
      parameters. The difference in tmax showed no clinical relevance. The new
      formulation is bioequivalent to the reference.

PMID- 7575746
TI  - Antihypertensive properties of a new long-acting angiotensin converting enzyme
      inhibitor in renin-dependent and independent hypertensive models.
AB  - The antihypertensive properties of a new long-acting, angiotensin-I-converting
      enzyme (ACE) inhibiting agent, (2S,3aS,7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D
      glutamyl) octahydro-1H-indole-2-carboxylic acid (CAS 116662-73-8, DU-1777), were
      investigated orally in various experimental models of hypertension in comparison
      to a standard ACE inhibitor, lisinopril. The hypotensive potency of DU-1777 was
      not as marked as that of lisinopril in renin-dependent hypertensive models, i.e.,
      two-kidney one-clip renal hypertensive rats (2K-1C RHR) (ED-20mmHg: 3.1 versus
      1.0 mg/kg) or two-kidney two-clip renal hypertensive dogs (2K-2C RHD) (ED-20
      mmHg: 2.5 versus 1.0 mg/kg), though the actions of the two drugs were both long
      lasting and dose-related. When spontaneously hypertensive rats (SHR) were used,
      however, DU-1777 was as active as lisinopril (ED-20 mmHg: 17.9 versus 13.6
      mg/kg). The most distinguishing results with DU-1777 were its hypotensive effects
      in renin-independent hypertensive models. In contrast to lisinopril, the drug
      produced a sustained and dose-related hypotensive effect in DOCA salt
      hypertensive rats (DOCA-HR) and one-kidney one-clip renal hypertensive rats (1K
      1C RHR). There exists an inconsistency between the long duration of the agent's
      hypotensive action in all tested hypertensive models and its short duration of
      ACE inhibiting activity as demonstrated both in vivo and ex vivo. The sustained
      antihypertensive action of DU-1777 cannot be reasoned solely with respect to ACE
      inhibition, suggesting some additional mechanisms of action yet to be defined.

PMID- 7575747
TI  - Antihypertensive effect of levcromakalim in patients with essential hypertension.
      Study by 24-h ambulatory blood pressure monitoring.
AB  - Levcromakalim (BRL 38227, CAS 94535-50-9) is a new antihypertensive drug with
      vasodilator activity due to activation of potassium channels in vascular smooth
      muscle. In this study, we treated 14 patients with essential hypertension on an
      out-patient basis to investigate the antihypertensive effect of levcromakalim by
      24-h blood pressure monitoring for a 12-weeks treatment period. Levcromakalim
      significantly lowered blood pressure for 24 h without affecting standard
      deviation, range of variation and pulse rate. When 24-h monitoring period was
      divided into daytime (6:00-22:00) and nighttime (22:30-5:30), there were no
      statistically significant differences in magnitude of fall in blood pressure at
      night between baseline and end of treatment values. Four patients (28.5%)
      reported 6 adverse events, including headache, facial hot flushes, oedema and
      floating feeling. All symptoms were mild or moderate. These data show that
      levcromakalim controls ambulatory blood pressure both in the daytime and
      nighttime without changing the circadian rhythm of blood pressure, and suggest
      that levcromakalim will be an efficacious and safe antihypertensive drug.

PMID- 7575749
TI  - Pharmacokinetics of the new oral blood glucose-lowering agent (-)-2-(4-tert.
      butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt in mice, rats and
      dogs.
AB  - The pharmacokinetic behavior of the alpha-activated carbonic acid (-)-2-(4-tert.
      butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt ((-)-BM 13.1074-Na)
      was examined in ob/ob mice, rats and dogs. By applying an enantioselective HPLC
      method, the in vivo stability of the administered (-)-enantiomer could be
      demonstrated in all tested species. After oral administration the compound was
      absorbed quickly and maximum plasma levels were reached within 1 h (ob/ob mice
      and rats) and 3 h (dogs), respectively. In dose proportionally studies in ob/ob
      mice, with doses of 0.25 and 1 mg/kg, a clear non proportional-increase of the
      plasma levels was observed. The terminal half-lives of (-)-BM 13.1074 after
      multiple dosing are approx. 30 h in ob/ob mice, 9 h in rats and approx. 380 h in
      dogs. The average effective plasma concentration in ob/ob mice is found to be
      43.5 mg/l; minimal toxic concentrations are 58.8 mg/l in rats and 105.6 mg/l in
      dogs, respectively.

PMID- 7575750
TI  - Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic
      acid.
AB  - Insulin resistance of skeletal muscle glucose uptake is a prominent feature of
      Type II diabetes (NIDDM); therefore pharmacological interventions should aim to
      improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA),
      a natural occurring compound frequently used for treatment of diabetic
      polyneuropathy, enhances glucose utilization in various experimental models. To
      see whether this compound also augments insulin mediated glucose disposal in
      NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/500 ml NaCl, n = 7) or
      vehicle only (500 ml NaCl, n = 6) during a glucose-clamp study. Both groups were
      comparable in age, body-mass index and duration of diabetes and had a similar
      degree of insulin resistance at baseline. Acute parenteral administration of ALA
      resulted in a significant increase of insulin-stimulated glucose disposal;
      metabolic clearance rate (MCR) for glucose rose by about 50% (3.76 ml/kg/min =
      pre vs. 5.82 ml/kg/min = post, p < 0.05), whereas the control group did not show
      any significant change (3.57 ml/kg/min = pre vs. 3.91 ml/kg/min = post). This is
      the first clinical study to show that alpha-lipoic acid increases insulin
      stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential
      use as an antihyperglycemic agent require further investigation.

PMID- 7575752
TI  - [Effective prevention of indomethacin-induced gastroduodenal mucosal lesions with
      roxatidine acetate].
AB  - In this randomized single-blind cross-over study the gastroduodenal damaging
      effect of indometacin 75 mg bid alone and in combination with roxatidine acetate
      (CAS 78628-28-1, Roxit) 75 mg nocte or 75 mg bid was evaluated in 12 healthy male
      volunteers. Prior to the start of the three therapeutic periods subjects
      underwent endoscopic examination to exclude gastroduodenal mucosa lesions. On
      days 7 and 14 of therapy 2 h after the application of the last indometacin dose
      subjects underwent endoscopy again. The 7- and 14-days administration of
      indometacin 75 mg bid, indometacin 75 mg bid plus roxatidine 75 mg nocte and
      indometacin 75 mg bid plus roxatidine 75 mg bid led to gastroduodenal mucosa
      lesion scores of 1.67 +/- 0.40 and 2.00 +/- 0.35, 1.33 +/- 0.28 and 1.50 +/-
      0.29, 0.42 +/- 0.23 and 1.00 +/- 0.33 (mean +/- SEM), respectively. These
      differences were statistically significant when comparing indometacin 75 mg bid
      versus indometacin 75 mg bid plus roxatidine 75 mg bid (p < 0.004 and < 0.008,
      respectively). This study shows that roxatidine acetate represents an effective
      alternative in the prophylaxis of NSAID-induced gastroduodenal mucosa lesions.

PMID- 7575748
TI  - Effect of calcium channel antagonists in modifying the inhibitory influence of
      adenosine on insulin secretion.
AB  - The present work was performed to study the effect of two calcium channel
      antagonists, namely verapamil (CAS 52-53-9) and nifedipine (CAS 21829-25-4) in
      modifying the inhibitory influence of adenosine on insulin secretion from
      isolated rat pancreatic islets. The combined effect of adenosine and these agents
      on serum insulin and glucose levels in vivo was also investigated. Both verapamil
      and nifedipine at 100 mumol/l and 1 mumol/l, respectively, produced a significant
      inhibition of glucose-stimulated insulin secretion from pancreatic islets.
      Combination of these agents with adenosine 10 mumol/l did not modify the
      inhibitory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b.wt.)
      and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prior to glucose
      loading produced a significant increase in serum glucose with an accompanied
      decrease in serum insulin levels. Concurrent administration of verapamil with
      adenosine neither affected the hyperglycaemic nor the hypoinsulinaemic effects of
      adenosine, whereas combined administration of nifedipine and adenosine decreased
      the hyperglycaemic effect of adenosine but not its hypoinsulinaemic effect. These
      results may indicate that these calcium channel antagonists do not interact with
      adenosine receptors which mediate its inhibitory effect on insulin secretion.

PMID- 7575751
TI  - [Absorption of di-linoleoylphosphatidylcholine after oral administration].
AB  - Essentiale and Lipostabil contain "essential" phospholipids from the soybean,
      mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is
      considered as the main active ingredient. A single oral dose of d15-DLPC loaded
      with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1
      position was given to volunteers. Sera from 11 blood samples taken within 48 h
      after application were examined by means of mass spectrometry with regard to d9
      choline and d6-linoleic acid in the 1- and 2-position of serum
      phosphatidylcholines (PC) as well as in the serum triglycerides. d9-choline, i.e.
      the total of d15-PC and d9-PC, showed maximum values of 5.6% of the total serum
      PC concentration. Normally, about 1.3% of PC in the human serum is DLPC. Serum 1
      linoleoyl-PC was increased by 32-40% after oral application of d15-DLPC. A minor
      uptake of d6-linoleic acid into the 2-position of serum PC, which is rich in
      linoleic acid, and into the serum triglycerides was observed with peak values of
      2.3% and 6.1%, resp. The uptake of polyunsaturated PC species like DLPC and 1
      linoleoyl-PC into the liver after oral application of drugs containing such
      species in high amounts like "essential" phospholipids with about 50% of DLPC let
      expect therapeutic effects on membranes into which this special species is
      incorporated.

PMID- 7575753
TI  - Effect of ibudilast on ciliary activity of human paranasal sinus mucosa in vitro.
AB  - The effect of ibudilast (CAS 50847-11-5, 3-isobutyryl-2-isopropylpyrazolo[1,5
      a]pyridine, KC-404), an anti-asthmatic drug, on ciliary beat frequency (CBF) of
      human paranasal sinus mucosa was examined in vitro. Ciliary activation was
      observed after a 10-min exposure to 4.6 x 10(-6) mol/l ibudilast. Ibudilast dose
      dependently increase CBF at the concentrations ranging from 4.6 x 10(-7) mol/l to
      4.6 x 10(-5) mol/l. Propranolol inhibited ciliary activity induced by ibudilast;
      however, neither indometacin nor verapamil affected the activation of ibudilast
      on CBF. Platelet activating factor (PAF) and Leukotriene D4 (LTD4) are chemical
      mediators inducing mucosal dysfunction and damage. Ibudilast prevented ciliary
      inhibition induced by PAF and LTD4. These findings indicated that ibudilast
      activates CBF and inhibits the effect of PAF and LTD4 on ciliated cells, and
      consequently improves the pathogenesis of allergic disorders such as the
      inhibited mucociliary transport system and airway hyperresponsiveness.

PMID- 7575755
TI  - Effects of peptide T derivatives on the proliferation of cultured human
      keratinocytes.
AB  - [D-Ala1]peptideT-amide, the linear hexapeptide H-Thr-Hse-Asn-Tyr-Thr-Asp-OH (LPT)
      and its cyclic analog, cyclo(-Thr-Hse-Asn-Tyr-Thr-Asp-) (CPT), were tested for
      their effects on the proliferation of cultured normal human keratinocytes (KTs)
      in comparison with vasoactive intestinal peptide (VIP). [D-Ala1]PT-NH2, LPT and
      VIP (all 0.1 mumol/l) increased the cell number in KT cultures, whereas CPT was
      ineffective. The VIP antagonist [N-Ac-Tyr1,D-Phe2]GRF (1-29)-NH2 significantly
      inhibited the VIP effects on KTs. On the other hand this antagonist did not
      affect the peptide T (PT) compounds-induced stimulation of KTs, providing
      indirect evidence that the mitogenic effects of VIP and PT peptides are probably
      mediated via different receptors.

PMID- 7575754
TI  - Pharmacokinetics of ibuprofen following a single administration of a suspension
      containing enteric-coated microcapsules.
AB  - The relative bioavailability of ibuprofen (CAS 15687-27-1) was investigated
      following a single administration of a suspension containing enteric-coated
      microcapsules (A) in comparison to a rapid-release film-coated tablet (B) and a
      sustained-release tablet (C). The study was carried out in a three-way crossover
      design in 9 healthy male volunteers. Each formulation contained 800 mg ibuprofen.
      Plasma concentrations of ibuprofen were determined with a specific HPLC method. A
      mean relative bioavailability of 0.96 (B) and 1.01 (C) was determined for the
      test formulation. Since the corresponding 90% confidence intervals were within
      the recommended limits, bioequivalence for the extent of bioavailability of the
      test formulation can be concluded. Differences in pharmacokinetics were observed
      for the rate-dependent parameters. For the test formulation, the highest mean
      maximum plasma concentration (54.3 micrograms/ml) was measured with a
      corresponding tmax of 1.9 h. For the reference formulations, mean peak plasma
      concentrations of 45.2 micrograms/ml after 2.6 h (B) and 25.7 micrograms/ml after
      5.6 h (C) were observed. Despite the enteric coating of the microcapsules, a very
      short lagtime of 0.03 h was determined for the suspension. For the other rapid
      release formulation (B), the lagtime was in a similar magnitude (0.11 h), while
      the absorption from the sustained-release tablet was clearly decelerated (tlag =
      0.97 h). In comparison to the other rapid-release formulation (B), significant
      higher amounts of the drug were absorbed from the test formulation (A) within the
      first hour.

PMID- 7575756
TI  - Comparison of fosfomycin and teicoplanin in serum bactericidal activity against
      staphylococci.
AB  - A serum bactericidal test was established employing human sera of volunteers
      after intravenous administration of fosfomycin (CAS 23155-02-4) and teicoplanin
      (CAS 61036-62-2) against 40 staphylococcal strains (20 Staphylococcus aureus and
      20 coagulase-negative staphylococci, 10 of each group being susceptible and 10
      being resistant to oxacillin). Median serum inhibitory titres were highest for
      fosfomycin against oxacillin-susceptible Staphylococcus aureus. In the three
      other groups of strains, the activity of fosfomycin was comparable to that of
      teicoplanin. The killing curves showed over 99% killing within 24 h for both
      antibiotics. Here, fosfomycin exerted a rapid killing activity within 4-6 h and
      was more effective in bacterial growth reduction. It can be concluded that
      fosfomycin and teicoplanin exerted comparable serum bactericidal antibacterial
      activity against staphylococci.

PMID- 7575757
TI  - Effects of 3-[N-(2-chlorobenzyl)amino]-6-(1H-imidazol-1-yl) pyridazine
      dihydrochloride on various aromatase enzyme systems and experimental breast
      cancer.
AB  - The effects of 3-[N-(2-chlorobenzyl)amino]-6-(1H-imidazol-1-yl)pyridazine
      dihydrochloride (CAS 124070-28-3, MFT-279) on various aromatase enzyme systems
      and experimental breast cancer were studied. MFT-279 inhibited the aromatase
      enzyme in vitro with an IC50 value of 2.39 nmol/l. On the other hand, MFT-279 had
      no effect on cytochrome P-450 dependent reactions of steroid biosynthesis. In
      pregnant mares' serum gonadotropin (PMSG)-treated female rats, the elevation of
      ovarian aromatase activity was significantly suppressed by the oral treatment
      with MFT-279 at 10 and 20 mg/kg. When MFT-279 (20 mg/kg) was orally given to 9,10
      dimethyl-1,2-benzanthracene (DMBA)-treated female rats once a day for 28 days,
      regression of tumors was observed. These results suggest that MFT-279 may be
      useful for the endocrine therapy of hormone dependent mammary carcinoma.

PMID- 7575758
TI  - In vitro studies on the immunomodulating effects of polypodium leucotomos extract
      on human leukocyte fractions.
AB  - The in vitro effect of Anapsos, a water based extract of the naturally occurring
      fern Polypodium leucotomos (calagualine), on human leukocyte fractions was
      investigated. Calagualine inhibited interleukin-2 secretion and concanavalin A
      (Con A) stimulated proliferation of T-lymphocytes in a concentration dependent
      manner. In contrast, a greatly enhanced secretion of IL-1 alpha, IL-1 beta and
      tumor necrosis factor alpha was induced suggesting a stimulation of monocytes and
      dendritic cells also present in this system. Endotoxin induced stimulation was
      excluded. Also in the absence of Con A, calagualine stimulated cytokine
      production. The presented data show for the first time that calagualine exerts an
      immunomodulating effect on leukocyte fractions, paving the way for further
      detailed studies related to possible clinical efficacy.

PMID- 7575759
TI  - Quantitative determination of lectins in mistletoe preparations.
AB  - Assay of lectins in mistletoe preparations was based on an improved and validated
      version of ELLA (enzyme-linked lectin assay) to meet the requirements given in
      the guidelines for drug tests. The monoclonal antibody used has more than 90%
      cross reactivity with the three known mistletoe lectins, so that total lectin
      content is determined with much greater accuracy. With the detection and
      quantitative analysis limit below 5 ng/ml and a linear measuring range of 5-50
      ng/ml, dosages in therapeutic range can be assayed. Tests to establish the
      accuracy of the analytical method showed that up to 26% of lectin activity is
      suppressed by other constituents of the extract, so that the recovery must be
      taken into account. The recovery increases following ultrafiltration to remove
      low-molecular constituents. Analysis for precision gave a variation coefficient
      of < or = 7.7% and a confidence interval < or = 5.7% (p = 0.05) for total lectin
      concentrations of approx. 250 ng/ml. This level of precision, which is good for
      an immunologic assay, makes it possible to standardize mistletoe preparations.

PMID- 7575760
TI  - Immunoregulatory effects of the herba Epimediia glycoside icariin.
AB  - The in vitro effects of the Chinese Herba Epimediia glycoside icariine (ICA), a
      chinese herbal extract, on human immune responses were investigated. ICA induced
      a weak and delayed proliferation of peripheral blood mononuclear cells from
      healthy donors when compared to phytohemagglutinin. Both T- (TCR alpha beta+) and
      B cells were the ICA-responding cells. Within T-cells, the relative proportion of
      CD4-8+ cells increased but that of CD4+8- cells decreased. ICA in certain
      concentrations could increase lymphokine-activated killer cell (LAK) activity
      (0.1 to 1.0 microgram/ml) in both tumor patients and healthy donors, and natural
      killer cell (NK) activity (1.0 to 5.0 micrograms/ml) in tumor patients. Moreover,
      ICA stimulated the production of tumor necrosis factor-alpha in monocytes from
      healthy donors. These findings provide evidence that ICA could be applied to
      adoptive immunotherapy. Generation of LAK cells in presence of an appropriate
      dose of ICA might be superior to interleukin-2 alone.

PMID- 7575763
TI  - [The Candida infected hen's egg. An alternative test system for systemic
      anticandida activity].
AB  - The Candida infected, embryonated hen's egg is a realistic complement for the
      model of the Candida infected mouse and can be used in the search for new
      systemically active antimycotics. This alternative method is rapid, sensitive
      convincing and inexpensive. The use of the embryonated hen's egg in an anti
      Candida screening can reduce the use of small laboratory animals to a
      considerable amount. Thus, with the help of this new method pain and suffering of
      animals can be reduced in a part of the biologic-medical research in the sense of
      the animal protection law.

PMID- 7575762
TI  - Biochemical and pharmacokinetic aspects of oral treatment with chondroitin
      sulfate.
AB  - Chondroitin sulfate (Condrosulf) was characterized for structure, physiochemical
      properties and purity. This glycosaminoglycan has a relative molecular mass of
      about 14,000, a sulfate-to-carboxyl ratio of 0.95 due to the high percentage of
      monosulfated disaccharides (38% 6-monosulfate and 55% 4-monosulfate) and a low
      amount of disulfated disaccharides (1.1%) inside the polysaccharide chains. No
      other glycosaminoglycans were detected in the preparation. Chondroitin sulfate
      was labelled by reduction with sodium 3H-borohydride and administered by oral
      route in the rat and dog. More than 70% of radioactivity was absorbed and found
      in urine and tissues. The plasma radioactivity was fractionated by size-exclusion
      chromatography in three fractions: radioactivity associated with high,
      intermediate and low molecular mass compounds. The peak value of the
      concentration of high molecular mass radioactivity compounds in plasma was
      reached after 1.6 and 2.1 h for the rat and dog, respectively. After 36 h the
      high molecular mass radioactivity compounds were still present in plasma of dog
      and rat. After 24 h radioactivity was higher in the intestine, liver, kidneys,
      synovial fluid and cartilage than in other tissues. Condroitin sulfate was orally
      administered to man (healthy volunteer) in a single daily dose of 0.8 g and in
      two daily doses of 0.4 g. The results showed that both forms of administration
      determined a significant increase of plasma concentration of chondroitin sulfate
      as compared with predose value over a full 24 h period. Elimination constant
      values and tmax (of the first administration in the case of fractionated dose)
      were almost the same for the two administrations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7575765
TI  - And away we go!

PMID- 7575766
TI  - Speech-language pathology assistants. A discussion of the proposed guidelines.

PMID- 7575767
TI  - Managed care 101. Introducing managed care into the curriculum.

PMID- 7575764
TI  - Intent and coincidence in pharmaceutical discovery. The impact of biotechnology.
AB  - Drug research developed around a purpose: the cure of diseases. This intent to
      cure, however, offered no clue to the understanding of diseases and to their
      treatment. Instead such guidance had to come from scientific disciplines which
      laid the foundations for drug research and offered specific opportunities for the
      solution of therapeutic problems. In the sequence of their appearance, these
      scientific disciplines were: chemistry, pharmacology/physiology, microbiology,
      biochemistry and molecular biology. It can be shown that new therapeutic classes
      of drugs like muscle relaxants, diuretics, L-dopa, antibiotics, recombinant
      proteins, monoclonal antibodies and others were generated on the basis of
      scientific opportunities rather than therapeutic need. All of these drugs were
      created within the confines of a chemical paradigm of medicine and drug therapy.
      We are now witnessing the entry of a new informational paradigm into medicine
      which is most prominently represented by genomic sciences. This paradigm will
      bring two important changes to the therapy of diseases. First, molecular biology
      has matured to such a degree that it can now study complex genomes and their
      functionality in complex organisms such as humans. Therefore, results from these
      studies no longer have to be translated into the context of medicine: they are
      already within this context. Secondly, drug therapy which used to be largely
      symptomatic, will now aim at targets which are closer to the causes of diseases
      than previously. Therapeutic progress, which used to be indirect, conjectural and
      coincidental, is about to become more directed, definitive and intentional. At
      least from the limited and utilitarian perspective of medicine, drug discovery
      will be more often based on intent rather than coincidence. But industry and, for
      that matter, society as a whole should not forget that this situation has come
      about through the evolution of science which was not, and can never be,
      predictable.

PMID- 7575768
TI  - Everything's up-to-date in Kansas. An innovative MA speech-language pathology
      curriculum.

PMID- 7575761
TI  - Bioequivalence of two oral cyclosporine preparations.
AB  - A comparison of bioequivalence of two cyclosporine (CAS 59865-13-3) preparations
      was performed. Ten cyclosporine treated patients with transplanted kidneys were
      included. Criteria were successful transplantation and minimum period from
      transplantation of at least 6 months. Two months before the experiment,
      cyclosporine concentrations had to be in therapeutic range without significant
      oscillation, and kidney function stabile. There had to be no signs of
      cyclosporine nephrotoxicity. During the objective biochemical analysis it was not
      allowed to find malfunction in any of the patient's organ important for
      cyclosporine pharmacokinetics. Cyclosporine concentrations in whole blood were
      measured with a specific fluoroimmunoassay. Cyclosporine and metabolites
      concentrations were measured with radioimmunoassay with non-specific antibody.
      Mean value and standard deviations and shape of distribution were calculated for
      all numeric data of patients, measured biochemical and other laboratory
      parameters. Variance analysis for all measured cyclosporine concentrations
      according to sampling times (C0 to C12, maximal concentrations C(M), time to
      maximal concentrations t(M), times of absorption delaying t(Lag) and area under
      the measured concentration curves (AUC) were statistically checked. According to
      these data it is concluded that the preparations are bioequivalent; a time to
      reach maximum concentration was slightly shorter for test preparation (2.5 and
      3.2 h, respectively), but not statistically significant. There are no significant
      differences between the areas under the concentration curves (1667 and 1665
      ng.h/ml, respectively). After the calculation of pharmacokinetic parameters of
      concentration data measured by a non-specific method a significant difference for
      areas under concentration curves was seen (3709 and 4600 ng.h/ml,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575769
TI  - You just can't keep a good person down!

PMID- 7575770
TI  - Treatment outcome: did the pieces fit?

PMID- 7575772
TI  - Histologic features of atherosclerosis and hypertension from autopsies of young
      individuals in a defined geographic population: the Bogalusa Heart Study.
AB  - Histologic features of arterial intima have been quantified at autopsy by
      morphometric methods in 66 individuals aged 6-30 years, in whom cardiovascular
      risk factors had been measured prospectively prior to death. Measures of serum
      cholesterol were found to correlate significantly with the extent of foam cell
      infiltration seen in paraffin sections and the intensity of lipid staining in
      frozen sections of the abdominal and thoracic segments of the aorta. A similar
      correlation in the coronary arteries was weak and inconsistent. Blood pressure
      was significantly correlated with foam cells and stainable lipid in the abdominal
      but not the thoracic segment of the aorta. A similar correlation in the coronary
      arteries was significant, but only in males, and most consistently in the black
      males. Intimal thickness of the coronary arteries showed sporadic and weak
      correlations with blood pressure and lipids; however, a strong and consistent
      correlation was seen between coronary intimal thickness and hyalinization of
      renal arterioles. With many statistical tests carried out on a limited data set,
      some particular details are, no doubt, spuriously significant; however, some
      persistent patterns are beginning to emerge. The reproducible findings support
      the concept that prospective measurements of blood pressure and serum lipids are
      associated with a degree of structural characteristics present in children and
      young adults. Moreover, the observed structural characteristics, specifically the
      deposition of lipids in the intima of coronary arteries and aorta, are likely to
      reflect variations in the rates of progression of atherosclerosis.

PMID- 7575771
TI  - Long-term efficacy and tolerability of simvastatin in a large cohort of elderly
      hypercholesterolemic patients.
AB  - The long-term efficacy and tolerability of simvastatin, a 3-hydroxy-3
      methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitor, was assessed during a
      24-month follow-up period in 168 elderly hypercholesterolemic patients. After
      completing a 4 week double blind dose ranging study with simvastatin, 47 males
      and 122 females over 62 years of age with type II hyperlipidemia, a total
      cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease
      were included in this extended study. A total of 159 patients completed the 12
      month follow-up period and 141 patients were monitored over the full 24 months.
      All patients were started on 10 mg simvastatin once daily and the dosage was
      increased until the target levels of low density lipoprotein (LDL) cholesterol
      between 2.3 mmol/l (90 mg/dl) and 3.6 mmol/l (140 mg/dl) were reached. Fifty
      percent of patients reached the targeted LDL cholesterol goal of < 3.6 mmol/l
      (140 mg/dl) during the study. At study completion, 65 patients (39%) were taking
      40 mg simvastatin per day, 56 patients (33%) 20 mg, 42 patients (25%) 10 mg and 5
      patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant
      lipid lowering therapy. Over 2 years, the mean decrease in LDL cholesterol ranged
      from 36% to 38%, the median decrease in triglycerides was 12% to 19% and the mean
      increase in high density lipoprotein (HDL) cholesterol ranged from 9% to 10%,
      respectively. Seven patients discontinued simvastatin because of adverse clinical
      or laboratory events, but only in two (1.1%) was this considered to be drug
      related. Side-effects were mild and most frequently gastrointestinal in nature.
      Mean changes in asparate aminotransferase (AST) were not significantly different
      from zero and mean changes in alanine aminotransferase (ALT) and creatine
      phosphokinase (CPK) showed a small increase. We conclude that simvastatin is an
      efficacious and well-tolerated treatment for hypercholesterolemia in elderly
      individuals for extended periods.

PMID- 7575773
TI  - Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed
      rabbit.
AB  - While T helper cell infiltration is an early event in the development of
      atherosclerosis in cholesterol-fed rabbits, their functional contribution to
      atherogenesis is not clear. To investigate their role, T cell activation was
      blocked with cyclosporine A (CsA) in New Zealand White (NZW) rabbits fed a 1%
      cholesterol diet. CsA was administered at a dose of 16 mg/kg body weight,
      intramuscularly every second day, resulting in circulating whole blood levels of
      460 +/- 39 micrograms/l. After 4 weeks on the cholesterol diet, untreated rabbits
      developed atherosclerotic plaques covering 74.4% +/- 3.5% of their aortic arch,
      19.8% +/- 7.8% of their thoracic aorta and 19.8% +/- 6.2% of their abdominal
      aorta. T cells were observed in plaques of their aortic arches (CD5 positive,
      11.1 +/- 7.3 cells/mm2; CD4 positive, 9.9 +/- 4.9 cells/mm2) by
      immunofluorescence using monoclonal anti-rabbit CD5 and CD4 antibodies. Rabbits
      treated with CsA developed significantly less extensive plaques after 4 weeks
      (aortic arch 33.0% +/- 6.2%, P < 0.001; thoracic aorta 6.3% +/- 1.5%, P < 0.05;
      abdominal aorta 2.7% +/- 0.5%, P < 0.005) than untreated rabbits. No CD4 or CD5
      positive cells were observed in their plaques. Treatment with CsA did not affect
      the weight gain of rabbits or reduce their serum cholesterol levels. Circulating
      T cell numbers and subsets were unaffected. These studies suggest that inhibition
      of T cell activation prevents their localisation in plaques and reduces the
      extent of early lesions, suggesting a role for T cells in the initiation of
      atherosclerosis.

PMID- 7575775
TI  - Altered erythrocyte membrane band 3 profile as a marker in patients at risk for
      cardiovascular disease.
AB  - The aim of this study is to evaluate the correlation between a rise in blood
      neutrophil concentration and cellular and molecular changes of erythrocytes,
      among populations presenting an increased risk of cardiovascular disease (CVD). A
      population of men aged 20-65 years was used which included 22 post-myocardial
      infarction individuals (< 48 h), 24 survivors of myocardial infarction (> 3
      months), 12 hypertensive individuals and 29 individuals presenting normal
      haematological values and normal lipid profile. The lipid profile parameters used
      to ascertain increased risk of CVD included triglycerides (TG), total cholesterol
      (Chol), high-density lipoprotein cholesterol (HDLc), low-density lipoproteins
      cholesterol (LDLc) and apolipoproteins A1 (Apo A1) and B (Apo B). The
      hematological parameters measured were concentration of total white blood cells
      (WBC) and of the several leukocyte types; concentration of red blood cells (RBC);
      hematocrit (Ht); hemoglobin concentration (Hb); mean cell volume (MCV); activity
      of erythrocyte glucose-6-phosphate dehydrogenase (G6PD); band 3, its aggregates
      and fragments in erythrocyte membranes, the percentage of membrane-bound
      hemoglobin (MBH), and the linkage of immunoglobulin G (IgG) to erythrocyte
      membrane. We found that the MBH and the band 3 profile is different in control as
      compared to pathological groups and that, as expected, the aggregation of band 3
      promotes the linkage of IgG to the erythrocyte membrane. A negative correlation
      was shown between total neutrophils and both total RBCs and erythrocyte G6PD
      activity. We suggest that the erythrocyte, a cell that undergoes and accumulates
      oxidative and proteolytic damage along its life span, may provide a useful model
      of oxidative and proteolytic stress in CVD and that band 3 may represent a useful
      marker of that stress.

PMID- 7575776
TI  - Gender differences of disturbed hemostasis related to fasting insulin level in
      healthy very elderly Japanese aged > or = 75 years.
AB  - We investigated the relationship between fasting insulin level and various
      hemostatic factors, including fibrinolytic factors (active plasminogen activator
      inhibitor-1 (PAI-1), tissue type plasminogen activator (tPA)-PAI-1 complex,
      plasmin-alpha 2-plasmin inhibitor (PIC), and D-dimer), coagulation factors
      (activated factor VII, factor VII coagulant activity and antigen, factor VIII,
      factor X, and fibrinogen), coagulation inhibitors (antithrombin III, heparin
      cofactor II, and protein C), and an acute phase marker (sialic acid) in 102
      healthy individuals aged > or = 75 years (46 men and 56 women). Active PAI-1
      levels had a significant negative correlation with PIC levels (r = -0.342, P =
      0.0006), indicating that PAI-1 influences in vivo fibrinolytic activity in the
      very elderly. Gender differences were found in the relationship between insulin
      and hemostatic abnormalities, with the insulin level being positively correlated
      with coagulation factors in men (factor VIII activity: r = 0.422, P < 0.01;
      factor VII activity: r = 0.386, P < 0.01) and with hypofibrinolysis in women
      (active PAI-1: r = 0.549, P < 0.0001). Insulin levels were positively correlated
      with the levels of factor VII antigen and factor VII activity in men (P < 0.01),
      but there was no correlation with activated factor VII levels. The fasting
      insulin level was also correlated with the levels of heparin cofactor II and
      sialic acid in men (P < 0.05). However, other hemostatic factors were not related
      to the insulin level in either sex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575777
TI  - DNA polymorphisms of the apoprotein B gene are associated with altered plasma
      lipoprotein concentrations but not with perceived risk of cardiovascular disease:
      European Atherosclerosis Research Study.
AB  - Three polymorphisms of the apoprotein B gene (XbaI, signal peptide
      insertion/deletion and the 3'-variable number of tandem repeats) selected on the
      basis of previously published reports as likely to be the most informative, were
      investigated in a cross-cultural study in Europe. Students from 14 universities,
      grouped for analyses into five regions, were recruited as cases (n = 682) if they
      had a paternal history of premature myocardial infarction. For comparison, twice
      the number of age- and sex-matched controls (n = 1312) were recruited from the
      same student populations. There were significant regional differences in allele
      frequencies of the XbaI and VNTR polymorphisms but not of the signal peptide.
      There were no significant differences in allele frequencies between cases and
      controls. Adjusted for age, gender and region, the lipoprotein concentrations
      differed significantly with genotype. The XbaI polymorphism was associated with
      differences in plasma cholesterol (P = 0.007), triglyceride (P = 0.050), apo B (P
      = 0.001) and LDL cholesterol (P = 0.01). An interaction between XbaI genotype and
      body mass index was observed on plasma triglyceride (P = 0.015) and apo B (P =
      0.005) concentrations. The signal peptide deletion allele was associated with
      increased plasma cholesterol (P = 0.03), apo B (P = 0.04) and LDL cholesterol (P
      = 0.02). The VNTR was not significantly associated with any of these variables
      although there was a significant genotype/status interaction in relation to HDL
      cholesterol (P = 0.001) and apo AI (P = 0.001) concentrations. We conclude that,
      although they are associated with significant differences in lipoprotein
      concentrations within- and between-populations, the apo B DNA polymorphisms
      studied are of less value as indicators of cardiovascular risk-factor status in
      the offspring of individuals affected by the disease.

PMID- 7575774
TI  - Antioxidants, von Willebrand factor and endothelial cell injury in
      hypercholesterolaemia and vascular disease.
AB  - The relationship between antioxidants and endothelial cell injury was examined in
      119 patients with (n = 48) or without (n = 71) vascular disease who were
      attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity,
      glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a
      specific endothelial cell product and marker of injury) and routine lipids were
      measured in the patients and from 58 healthy controls. Compared to controls,
      total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001)
      were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing
      patients with and without vascular disease, glutathione peroxidase was lower (P <
      0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there
      was no difference in levels of serum lipids or total antioxidant capacity. vWf
      and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We
      conclude that patients with hypercholesterolaemia have reduced antioxidant
      capacity and this is most severe in patients with clinically apparent vascular
      disease. This, linked to the finding of increased vWf in hypercholesterolaemia
      with highest levels in those patients with vascular disease, suggests that loss
      of antioxidant capacity may expose the vascular endothelium to excess oxidative
      damage. These results suggest a link between hypercholesterolaemia, impaired
      ability to resist free radical attack, and the development of atherosclerosis.

PMID- 7575778
TI  - Platelet-derived microparticles may influence the development of atherosclerosis
      in diabetes mellitus.
AB  - We investigated the association between low-density lipoprotein (LDL),
      triglycerides, and platelet activation in 18 patients with hypertension age 41-64
      years and 18 with diabetes mellitus aged 43-70 years. Platelet P-selectin
      positivity and the microparticle level (indicators of activation) were both
      significantly higher in the diabetics than in healthy controls (P-selectin: 28.0%
      +/- 7.5% vs. 7.3% +/- 4.2%, P < 0.001; microparticles: 1900 +/- 966 vs. 526 +/-
      158/10(4) platelets, P < 0.01). In contrast, there was no significant increase of
      either parameter in the patients with hypertension. Plasma microparticle levels
      were also significantly greater in the diabetics with high LDL levels than in
      those with low LDL levels (2375 +/- 949 vs. 1519 +/- 796/10(4) platelets, P <
      0.05), and in those with high rather than low triglyceride levels (2188 +/- 845
      vs. 1492 +/- 783/10(4) platelets, P < 0.05). However, platelet positivity for P
      selectin was not significantly different between these two subgroups.
      Microparticle and P-selectin levels both showed no significant difference between
      the hypertensive patients with high and low LDL or triglyceride levels. These
      results suggest that platelet-derived microparticles may participate in the
      development or progression of atherosclerosis in patients with diabetes mellitus.

PMID- 7575779
TI  - Effect of immunosuppressive drug regime on cardiovascular risk profile following
      kidney transplantation.
AB  - We have previously studied cardiovascular risk markers apolipoprotein (a)
      (apo(a)) and plasma fibrinogen in 146 control, 60 haemodialysis (HD), 53
      continuous ambulatory peritoneal dialysis (CAPD) and 66 renal transplant
      subjects. Fibrinogen concentration was higher in all 3 renal replacement groups
      compared to controls. Apo(a) was higher in the CAPD group only. We have now
      restudied those dialysis patients (24 HD, 16 CAPD) who have since undergone
      transplantation. Fibrinogen concentration remained elevated in CAPD patients
      (mean (SE) 3.9 (0.17) vs. 3.77 (0.20) grams/l) and increased in HD patients (2.88
      (0.16) vs. 3.72 (0.13) grams/l, P < 0.0001). Apo(a) fell in both groups (CAPD,
      geometric mean 287 vs. 151 U/l, P = 0.008; HD, 230 vs. 179 U/l, P = 0.013).
      Fibrinogen concentration was higher in the recent group compared to the original
      group (3.74 (0.11) vs. 3.19 (0.12) grams/l, P = 0.001). None of the 66 original
      patients received cyclosporin (cyA) compared to 35 of the 40 in the present
      study. In this recent group, patients maintained on prednisolone and azathioprine
      alone had significantly lower fibrinogen levels than those receiving cyA.
      Furthermore, the fall in apo(a) was smaller (31% vs. 74%) and the increase in
      apolipoprotein B (apo B) greater (0.55 (0.15) vs. 0.18 (0.05) grams/l, P = 0.014)
      in cyA-treated patients. CyA may have an adverse effect on cardiovascular risk
      profile in renal transplant recipients.

PMID- 7575780
TI  - Effect of fatty acid structure on neutrophil adhesion, degranulation and damage
      to endothelial cells.
AB  - Neutrophils have been implicated in ischaemic heart disease, unstable angina
      pectoris and acute myocardial infarction. Alterations in dietary levels of
      specific 18- and 20-carbon polyunsaturated fatty acids have significant clinical
      benefits in cardiovascular disease. However, to date there has been no concerted
      effort to identify the structural basis for polyunsaturated fatty acid-induced
      alterations in key neutrophil functions. We have investigated the influence of
      fatty acid structure and involvement of lipoxygenase/cyclooxygenase pathways on
      fatty acid-induced neutrophil functions. When neutrophils were incubated with 18
      carbon fatty acids containing one to four double bonds (10-33 mumol/l), a
      significant increase in adherence and release of specific granule constituents
      occurred compared with control cells. In general, as the number of double bonds
      in the 18-carbon fatty acid increased, so did its ability to stimulate these
      functions. There was less stimulation of adherence and specific granule release
      by 18:3(n-3) than its isomer 18:3(n-6). Smaller effects were seen on azurophilic
      granule release. A further increase in adherence and degranulation was observed
      with increasing carbon chain length (20:3(n-6) and 20:4(n-6)). Differences were
      found in the ability of isomers of 20:3 to stimulate neutrophil function. Of the
      fatty acids tested only 20:4(n-6) was able to induce significant neutrophil
      mediated endothelial detachment. Introduction of either internal hydroperoxy or
      hydroxyl groups into 20:4(n-6) abolished its adherence stimulating activity and
      considerably reduced its ability to stimulate release of both specific and
      azurophilic granules. Preincubation of neutrophils with either lipoxygenase
      (caffeic acid) or cyclooxygenase (indomethacin) inhibitors had no effect on
      20:4(n-6) stimulated function. These studies show that the number and position of
      double bonds, carbon chain length and oxidation state can be critical to the
      neutrophil stimulatory properties of these fatty acids.

PMID- 7575781
TI  - Basic fibroblast growth factor reverses atherosclerotic impairment of human
      coronary angiogenesis-like responses in vitro.
AB  - The influence of atherosclerosis on vascular growth in humans was evaluated in an
      in vitro model of angiogenesis. Coronary artery intima-media explants from
      patients (n = 10) with coronary artery disease (CAD) (in all cases Stary type V
      lesions) and patients without CAD (n = 10) were cultured in a collagen matrix
      containing serum-free medium. Endothelial cell growth from explants was organized
      as capillary-like microtubes (CLM); the sum of their lengths was morphometrically
      quantitated as an index of angiogenesis. CLM growth was suppressed in CAD
      explants (n = 120), the index values at two weeks averaging only 20% +/- 3% of
      non-CAD explants (n = 120, P < 0.001). Addition of exogenous basic fibroblast
      growth factor (bFGF) (10 ng/ml) stimulated CLM growth substantially more in the
      CAD than in the non-CAD group, whereas bFGF-neutralizing antibodies nearly
      abolished growth in both. Endothelial cells isolated from non-CAD coronary
      arteries exhibited in culture typical endothelial characteristics, including
      cobblestone appearance, staining for von Willebrand factor, CLM formation on
      Matrigel substrate, and sensitivity to bFGF and to bFGF-neutralizing antibody.
      Inhibition of cell replication by oxidized low-density lipoprotein (OxLDL) was
      reversed by bFGF. We conclude that human atherosclerosis is associated with
      impairment of angiogenesis-like endothelial growth and that decreased bFGF
      availability contributes to the impairment.

PMID- 7575783
TI  - Exposure to blood and body fluid: factors associated with non-compliance in
      follow up HIV testing among health care workers.
AB  - Due to lack of previous research, this study examined the factors associated with
      non-compliance in follow up human immunodeficiency virus (HIV) testing among
      health care workers after blood and/or body fluid exposure. A descriptive
      correlation design was used with 178 health care workers who did not return for
      recommended follow up HIV testing post-blood and/or body fluid exposure at three
      urban hospitals. The 36 question Likert scale was designed to measure the five
      concepts of the Health Belief Model: susceptibility, seriousness, benefit,
      barriers, and health motivation. The internal consistency reliability measured
      .48. Forty five subjects (25%) returned the questionnaire. The most significant
      factor determined to affect return rate for follow up testing was related to
      benefits and susceptibility (F = 4.57, df = 2.42, R = .42, P = .02). Return rate
      was most significantly correlated with the idea of decreasing the chance of dying
      from acquired immunodeficiency syndrome (AIDS) (r = .31, P = .04). Similar
      results of recommended future studies may indicate changes in post-exposure
      education or institutional policies and procedures.

PMID- 7575782
TI  - Familial defective apolipoprotein B-100 and myocardial infarction. The ECTIM
      study. Etude Cas-Temoins de l'Infarctus du Myocarde.

PMID- 7575784
TI  - The Family Medical Leave Act.

PMID- 7575785
TI  - Theories and trends in occupational health nursing: prevention and social change.
AB  - 1. Occupational health nursing has evolved against a background of changes in the
      workplace, health care delivery, and society. 2. One major change is the growing
      interest among employers for health promotion and wellness programs to manage
      health care costs. 3. The health Belief Model and levels of prevention provide a
      framework for health promotion and disease prevention programs at the worksite.
      4. Occupational health nurses, using a marketing strategy that incorporates the
      principles of product, price, placement, and promotion, will enhance their
      ability to provide successful programs.

PMID- 7575787
TI  - Social marketing: consumer focused health promotion.
AB  - 1. Social marketing provides a theoretical basis to increase awareness of
      preventable health conditions and to increase participation in wellness programs.
      2. The philosophy of social marketing underscores the necessity to be aware of
      and responsive to the consumer's perception of needs. 3. Social marketing is
      distinguished by its emphasis on "non-tangible" products such as ideas,
      attitudes, and lifestyle changes. 4. "Marketing mix" is a social marketing
      strategy that intertwines elements of product, price, place, and promotion to
      satisfy needs and wants of consumers.

PMID- 7575786
TI  - Fitness for duty policy: implementation in the workplace.
AB  - 1. Drug use is most prevalent among young adults representing the segment of our
      society entering the work force. 2. The "fitness for duty" policy stipulates that
      all employees assume responsibility to report to work in a fit condition and
      perform their jobs without increasing risk to themselves or others. 3. The
      supervisor focuses on observable behavior; the employee health practitioner
      completes a confidential medical evaluation; the EAP professional performs an in
      depth evaluation; and the human resources representative/manager evaluates the
      employee's continued employment. 4. After treatment and rehabilitation, the
      employer gains a productive, healthy, and substance free employee, and the
      employee gains by entering a program of sobriety supported by the organization.

PMID- 7575788
TI  - Shiftwork: the special challenges for women.
AB  - 1. Humans are designed to sleep at night and work during the day; thus, shiftwork
      is inherently non-physiological. The species has not yet evolved to the point of
      being able to adjust to a 24 hour day, despite society's demands. 2. Certain
      individuals may be better able to cope with the requirements of shiftwork than
      others. Women may be less able than men to do so because of the demands of home
      and family life and physiological differences. 3. Shifts can be designed to be
      more or less difficult for certain individuals. "Night owl" individuals might do
      best with evening shifts, "morning larks" with shifts starting in the early
      morning.

PMID- 7575789
TI  - Workplace violence.
AB  - Research related to workplace violence is in its infancy. The epidemiologic data,
      which are just beginning to appear in the literature, show that workplace
      violence is a growing concern for employers and employees. Experts provide
      suggestions on ways to prevent workplace violence, but the literature lacks
      studies that examine the use or results of such activities. Included in these
      suggestions is the need to implement violence prevention policies and procedures,
      security controls, screening, employee assistance programs, and workplace
      education/training for employees and managers. Occupational health nurses are in
      a unique position to provide violence prevention programs in the workplace.

PMID- 7575790
TI  - Reflections: growth and excellence in occupational health nursing.

PMID- 7575792
TI  - Health promotion communications system: a model for a dispersed population.
AB  - 1. Corporations with geographically dispersed populations need to provide
      flexible health promotion programs tailored to meet specific employee interests
      and needs. 2. Bell Atlantic developed a dispersed model approach based on the
      transtheoretical model of behavior change. The key to this model is to identify
      at which stage the individual is operating and provide appropriate information
      and behavior change programs. 3. Components of the program include: health risk
      appraisal; exercise/activity tracking system; on line nurse health information
      service; network of fitness facilities; employee assistance programs; health
      library available by fax; health film library; network of health promotion
      volunteers; and targeted health and marketing messaged via corporate media.

PMID- 7575793
TI  - Comprehensive health promotion: opportunities for demonstrating value added to
      the business.
AB  - 1. Comprehensive health promotion is any intervention that attempts to move
      people toward a state of optimal health, including traditional disease prevention
      efforts. 2. Health promotion programs enhance employees' self responsibility,
      sense of balance with work, family, health, and social concerns, and ability to
      take action, all of which improve teamwork, innovation, quality, and creative
      thinking. 3. The design of a comprehensive health promotion program is directed
      by health goals or management goals, and based on data obtained by an assessment
      of all customers. 4. Health care cost reductions are more likely to be achieved
      when an array of programs are offered.

PMID- 7575791
TI  - Implementing corporate wellness programs: a business approach to program
      planning.
AB  - 1. Support of key decision makers is critical to the successful implementation of
      a corporate wellness program. Therefore, the program implementation plan must be
      communicated in a format and language readily understood by business people. 2. A
      business approach to corporate wellness program planning provides a standardized
      way to communicate the implementation plan. 3. A business approach incorporates
      the program planning components in a format that ranges from general to specific.
      This approach allows for flexibility and responsiveness to changes in program
      planning. 4. Components of the business approach are the executive summary,
      purpose, background, ground rules, approach, requirements, scope of work,
      schedule, and financials.

PMID- 7575795
TI  - Physical fitness and employee absenteeism: measurement considerations for
      programs.

PMID- 7575794
TI  - Reprographic paper workers: a preliminary study of occupational risk.
AB  - 1. The purpose of this descriptive retrospective study was to identify the
      prevalence of illness and medical problems among the reprographic paper employees
      which might be occupationally linked. 2. A telephone survey was developed and 162
      workers were interviewed about self reported health problems, occupational
      history, and demographics. 3. The findings of the study strongly suggest that
      prevalence of illness and medical problems among particular workers within the
      plant might be occupationally linked. 4. The most significant implication of this
      study is its ability to show clearly the pivotal role that occupational health
      nurses can play in identifying occupationally linked employee health problems
      through research.

PMID- 7575796
TI  - Listening.
AB  - Listening is a skill that few are taught and yet is essential to the successful
      operation of the occupational health service. Taking time to listen (even if that
      time is "not right now"), listening both verbally and nonverbally, and allowing
      speakers to tell their stories and discover the outcome or the solution to their
      problems are key components of effective listening. Attentive listening has the
      potential not only to facilitate progress in the health service but to foster a
      positive reputation for the occupational health nurse manager throughout the
      company.

PMID- 7575797
TI  - Correlation of serial blood lactate levels to organ failure and mortality after
      trauma.
AB  - To define the value of serial measurements of blood lactate levels after trauma,
      the present study investigated the correlation between blood lactate, mortality,
      and organ failure in 129 trauma patients, including 100 intensive care unit (ICU)
      survivors and 29 ICU fatalities. On admission, injury severity score (ISS) was
      higher and Glasgow coma score (GCS), revised trauma score (RTS), and trauma
      revised ISS (TRISS) were lower in the nonsurvivors than in the survivors. Serial
      arterial blood lactate levels were measured on admission and at least three times
      a day until normalization. Both initial lactate and highest lactate levels were
      higher in the nonsurvivors than in the survivors. Organ failure developed in 84
      (65%) of the 129 patients. Patients with organ failure had significantly lower
      RTS and TRISS. Initial lactate and highest lactate levels were significantly
      higher in patients with organ failure than without organ failure (3.4 [0.7 to
      12.7] versus 2.4 [0.4 to 7.6] mEq/L and 4.1 [0.7 to 12.7] versus 2.8 [0.4 to 8.9]
      mEq/L, respectively, both P < .01). The duration of hyperlactatemia averaged 2.2
      days in the former but 1.0 day in the latter patients (P < .01). The data
      therefore indicate that not only the initial or the highest lactate value but
      also the duration of hyperlactatemia can be correlated with the development of
      organ failure. These observations stress the importance of the initial
      resuscitation in the prevention of organ failure. Serial blood lactate
      measurements are reliable indicators of morbidity and mortality after trauma.

PMID- 7575798
TI  - Percutaneous needle cricothyroidotomy with repetitive airway obstruction.
AB  - To develop a technique for needle cricothyrotomy that mimics the normal
      respiratory cycle (using repetitive obstruction of the upper airway and
      relatively low flow oxygen through small catheters), a controlled trial in three
      anesthetized dogs was performed. Oxygen from a standard bottle and pressure
      reducer was delivered through the cricothyroid membrane at 0.36 L/kg/min, which
      is metabolically equivalent to 0.2 L/kg/min in an adult human. The upper airway
      was obstructed until the chest rose and then was unobstructed to allow
      exhalation. The animals were ventilated for 5 minutes to allow equilibration.
      Arterial PCO2 was measured after 2-minute periods of apnea and 3 minutes of
      ventilation, each repeated four times. The procedure was repeated in three other
      dogs at a flow of 0.18 L/kg/min to simulate a 50% air leak. Cricothyroid
      ventilation at 0.36 L/kg/min lowered the PCO2 from 65 mm Hg to 43 mm Hg, F = 258,
      P = .004. All PCO2 after 25 minutes were in the normal range. Ventilation at 0.18
      L/kg/min stabilized the PCO2 at approximately 1.5 times normal (67 mm Hg versus
      79 mm Hg for the preceding apnea, F = 77, P = .013). Flow rates achievable with
      18- to 20-gauge catheters and standard oxygen sources are adequate for
      cricothyroid ventilation when the airway is repetitively obstructed to allow a
      normal respiratory cycle.

PMID- 7575799
TI  - Comparison of cardiac output measurements by thermodilution and thoracic
      electrical bioimpedance in critically ill versus non-critically ill patients.
AB  - Thoracic electrical bioimpedance (TEB) has been proposed as an alternative to
      thermodilution (TD) for the measurement of cardiac output in settings such as the
      Emergency Department where invasive monitoring is not available. Validation
      studies comparing TEB with TD suggest a wide range of variability in the
      agreement between the two methods. This prospective study tests the hypothesis
      that this variability may be related to the severity of patient illness. Fifteen
      non-critically ill patients undergoing cardiac catheterization and 13 critically
      ill patients who underwent Swan-Ganz catheterization in the medical intensive
      care unit (MICU) were enrolled. Fifty-one pairs of data from the catheterization
      laboratory and 49 pairs of data from the MICU were obtained. The patients were
      graded retrospectively according to the APACHE II scoring system. The mean
      difference (bias) between TEB and TD results was calculated for each patient
      using the method suggested by Bland and Altman. A pooled t-test was performed to
      determine whether there was any significant difference between the APACHE II
      scores or cardiac output measurements obtained by TEB and TD in the two groups.
      APACHE II scores were 4.7 +/- 1.2 for the catheterization laboratory and 14.2 +/-
      5.0 for the intensive care unit patients (P < .001). The catheterization
      laboratory (cath lab) group bias was 0.23 +/- 2.19, whereas the MICU bias was
      .002 +/- 2.33. There was no significant difference in the bias between the two
      groups despite significant differences in the APACHE II scores. Standard
      deviations of the bias were less than 15% different from each other.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7575802
TI  - Heterotopic pregnancy after in vitro fertilization.
AB  - Maternal mortality related to ruptured ectopic pregnancy remains elevated. A case
      is presented of heterotopic pregnancy in a patient whose pregnancy was assisted
      with in vitro fertilization. The patient's diagnosis was delayed, potentially
      because of lack of tachycardia associated with the hypotension. The clinical
      presentation of heterotopic pregnancy is similar to that of ectopic pregnancy.
      The risk factors for heterotopic pregnancy are the same as those for ectopic
      pregnancy, with the addition of in vitro fertilization, which increases the risk
      substantially.

PMID- 7575801
TI  - Pediatric coin ingestion: a home-based survey.
AB  - To improve understanding of the natural history of pediatric coin ingestions, an
      anonymous, home-based mail survey of parents followed by a five-physician private
      pediatric practice in suburban Maryland was conducted. Of 2,263 families
      surveyed, 798 (35.3%) responded, representing 1,510 children. Sixty-one (4.0%,
      95% confidence interval: 3.1% to 5.1%) children had swallowed a coin, at a mean
      age of 2.8 years. Fifty-two (85%) coin ingestions were managed at home, usually
      without calling a physician or poison control center. Only 9 (15%) children were
      examined by a physician. No child (95% confidence interval: 0% to 4.9%) underwent
      a removal procedure or had an adverse outcome. Most coin ingestions were found to
      have been managed at home, often without calling a physician or poison control
      center. Hospital- or poison control center-based studies underestimate coin
      ingestion incidence and overestimate the frequency of complications.

PMID- 7575800
TI  - Educational and long-term therapeutic intervention in the ED: effect on outcomes
      in adult indigent minority asthmatics.
AB  - Minorities have increased morbidity and mortality rates resulting from asthma.
      The segment of minorities that is socioeconomically depressed often uses the
      emergency department (ED) as their primary site of medical care. For these
      reasons, we provided major long-term therapeutic intervention as well as
      intensive education in the ED for indigent adult African American asthmatics. We
      intervened in the cases of 30 patients who were frequent visitors to the ED over
      the previous 2 years. The intervention consisted of 1 hour of education in the ED
      before discharge regarding the prevention of asthma, the importance of decreasing
      inflammation as a means of improving asthma control, self-monitoring with a peak
      flow meter, and a demonstration of correct inhalation technique with metered-dose
      inhalers and a spacer device. Further, the intervention included management
      consistent with recent NIH Guidelines, stressing inhaled corticosteroids. After
      the intervention in the ED, patients were scheduled for follow-up asthma clinic
      visits. Outcome measures were ED visits and hospitalizations for 1 year after the
      ED intervention. Using the same inclusion/exclusion criteria, a retrospective
      control group of 22 patients for the same time period was compared with the
      intervention group. Before our intervention, the mean number of ED visits per
      patient for the previous 2 years was 4.4 +/- 2.7, and after the intervention, 2.6
      +/- 2.6 (P < .01). The control group did not show a difference in the number of
      ED visits (3.4 +/- 2.6 before and 3.5 +/- 2.7 after, P = .96). After the
      intervention, the mean number of hospitalizations decreased significantly in the
      study group (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575803
TI  - Rhabdomyolysis secondary to keyboard overuse: occupational hazard of the computer
      age.
AB  - A 33-year-old man presented with rhabdomyolysis with bilateral forearm pain and a
      profoundly elevated creatine phosphokinase. The cause of his illness appears to
      be computer keyboard overuse soon after a viral illness. This is the first case
      report directly linking rhabdomyolysis with keyboard overuse.

PMID- 7575806
TI  - Trauma: an annotated bibliography of the recent literature.

PMID- 7575804
TI  - Hemiballismus as a presenting sign of hyperglycemia.
AB  - A 53-year-old man arrived at the emergency department after the onset of
      progressive hemiballismus. This movement disorder was the only manifestation of
      his hyperglycemic state. Prompt recognition of the association of unusual
      movement disorders with nonketotic hyperglycemia will allow for prompt treatment.

PMID- 7575805
TI  - Cases in electrocardiography.

PMID- 7575807
TI  - Accuracy of radiograph interpretation in a pediatric ED.

PMID- 7575808
TI  - In vitro binding of lithium using the cation exchange resin sodium polystyrene
      sulfonate.

PMID- 7575809
TI  - Complete generator extrusion as a cause of pacemaker dysfunction.

PMID- 7575810
TI  - Spontaneous rectus sheath hematoma: ED diagnosis and management.

PMID- 7575813
TI  - Nebulized fenoterol versus i.v. aminophylline treatment of acute severe asthma.

PMID- 7575814
TI  - Primary hyperparathyroidism as a surgical emergency.

PMID- 7575812
TI  - Variceal bleeding due to segmental portal hypertension caused by chronic
      pancreatitis.

PMID- 7575811
TI  - Severe hypercalcemia presenting with multisystem organ failure.

PMID- 7575815
TI  - Percutaneous versus open methods in cricothyroidotomy and thoracostomy.

PMID- 7575817
TI  - Successful epidural blood patch 2 years after post-lumbar puncture headaches.

PMID- 7575818
TI  - CPAP: possible ED applications.

PMID- 7575819
TI  - Neurosyphilis presenting as refractory status epilepticus.

PMID- 7575820
TI  - The highest price of education.

PMID- 7575816
TI  - Emergency intubation with the combitube in a case of severe facial burn.

PMID- 7575821
TI  - Evaluation of the nonreactive positive contraction stress test prior to 32 weeks:
      the role of the biophysical profile.
AB  - A nonreactive positive contraction stress test in a pregnancy near term is an
      indication for delivery. Such nonreassuring antepartum testing combined with
      severe prematurity presents a management dilemma. Ideally, prolongation of
      selected pregnancies would allow time for corticosteroid therapy and fetal
      maturation. Prior to 32 weeks' gestation, we utilized the biophysical profile to
      select patients for continued intrauterine management as an alternative to
      immediate delivery. Continued surveillance was undertaken if the fetus had a
      reassuring biophysical profile score; immediate delivery by cesarean section was
      undertaken if the biophysical profile score was nonreassuring. This approach
      allowed a mean gain of 13 days in utero for the continued surveillance group.
      There was no evidence of further fetal compromise in this group based on
      umbilical cord pH or 5-minute Apgar scores. These data suggest that the
      biophysical profile can be safely used to prolong selected preterm pregnancies
      with nonreactive positive contraction stress tests without adversely affecting
      the initial neonatal metabolic status.

PMID- 7575822
TI  - Early meconium evacuation: effect on neonatal hyperbilirubinemia.
AB  - Delayed passage of meconium may increase enterohepatic circulation of bilirubin,
      which appears to be an important contributor to neonatal jaundice. To evaluate
      the effect of early meconium evacuation on neonatal hyperbilirubinemia, between
      January 1993 and December 1993, 265 healthy neonates were studied and randomly
      divided into two groups. Group 1 consisted of 130 neonates who received glycerin
      enema (1 mL of glycerin mixed with 1 mL of warmed normal saline) within 30
      minutes after birth and the same procedure was repeated at 12 hours of age. Group
      2 consisted of 135 neonates receiving no glycerin enema throughout their hospital
      stay. Determination of total serum bilirubin using capillary samples was
      performed daily for 7 days. Our data showed that 12 neonates (15.4%) in group 1
      and 18 neonates (13.3%) in group 2 had serum bilirubin level 15 mg/dL or higher
      and received phototherapy. We conclude that early evacuation of meconium by using
      glycerin enema within 30 minutes after birth and 12 hours after birth in order to
      reduce enterohepatic circulation of bilirubin has no effect on lowering peak
      serum bilirubin levels or on serum bilirubin concentrations in the first 7 days
      of life.

PMID- 7575823
TI  - Hemodynamic control of atrial natriuretic peptide plasma levels in neonatal
      respiratory distress syndrome.
AB  - To evaluate the contribution of the pulmonary and ductal hemodynamics on the
      cardiac atrial natriuretic peptide (ANP) synthesis and release in neonatal
      respiratory distress syndrome, serial blood samples for plasma C-terminal end,
      and the more stable N-terminal end (NT-proANP) of the propeptide were obtained.
      Simultaneous evaluation of the systolic pulmonary artery pressure (PAP) and
      magnitude of ductal shunting by the Doppler method were made of 37 distressed
      infants during the first 4 days of life. Both plasma ANP and NT-proANP rose after
      birth, peaked at 48 hours of age, and correlated significantly (r = 0.66; p <
      0.001; n = 78) with each other. The initially high systolic PAP and, since the
      systemic arterial pressure (SAP) did not change, the PAP/SAP ratio declined
      slowly during the study period, as did the magnitude of ductal left-to-right
      shunting after an initial increase during the first hours after birth. Plasma NT
      proANP had a positive correlation to the magnitude of ductal left-to-right
      shunting both during the first 2 and 4 days of life, but did not correlate with
      PAP, SAP, or PAP/SAP ratio during the same time periods. Eight infants with
      delayed closure of the ductus maintained elevated plasma NT-proANP values after
      the second day of life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575824
TI  - Prenatal diagnosis and management of fetal goiter caused by maternal Grave's
      disease.
AB  - We present a case of maternal Grave's disease associated with fetal goitrous
      hyperthyroidism. Fetal goiter was diagnosed by ultrasound and diagnosis of fetal
      hyperthyroidism was established by umbilical blood sampling. Fetus was
      successfully treated by increasing maternal propylthiouracil dosage. Fetal
      thyroid status was normal at birth. Role of sonography and umbilical blood
      sampling in management of fetal goiter complicated with maternal Grave's disease
      is discussed.

PMID- 7575826
TI  - Neonatal intussusception misdiagnosed as necrotizing enterocolitis.
AB  - Two premature infants with abdominal distension, respiratory distress syndrome,
      and sepsis were initially diagnosed and treated for necrotizing enterocolitis
      (NEC). After failure of conservative measures, a diagnosis of intussusception was
      contemplated. This pitfall in the management of NEC, with medical treatment and a
      poor response, has been increasingly reported.

PMID- 7575827
TI  - Fasting plasma glucose and glycosylated plasma protein at 24 to 28 weeks of
      gestation predict macrosomia in the general obstetric population.
AB  - The purpose of this study was to modify the traditional gestational diabetes
      screening process in order to provide a test that might more reliably detect
      those women at risk of delivering a macrosomic infant despite a negative test for
      gestational diabetes mellitus (GDM). Pregnant women (n = 160) were screened for
      GDM at 24 to 28 weeks' gestation using the traditional 50 g glucose challenge
      test (GCT). In addition, glycosylated hemoglobin, glycosylated serum protein, and
      glycosylated plasma protein (GPP) were analyzed from blood drawn at this same
      time. If the patient's challenge test was positive (140 mg/dL or higher), a 100 g
      oral glucose tolerance test (OGTT) was performed. Twenty-three women had a
      positive GCT (14.4%) and five (3.13%) were excluded from further study because
      they received treatment for gestational diabetes based on a positive OGTT. None
      of the GCT-negative or the GCT-positive-OGTT-negative patients received
      treatment. Gestational age at delivery, infant gender, and birthweight were
      retrieved from birth records. Although several correlations with infant
      birthweight were found, the fasting plasma glucose (FPG) and GPPs proved most
      significant. The FPG on the OGTT significantly correlated with infant birthweight
      (p < 0.001; r = 0.94). A value greater than 90 mg/dL proved to be 100% sensitive
      and 64% specific for infant birthweight more than 4000 g. The relationship of the
      GPP and subsequent infant birthweight was also significant (p < 0.001; r = 0.81).
      A GPP greater than 23% proved to be 100% sensitive in predicting birthweight
      above 4000 g (11 of 11 infants); however, the test had a 52%
      specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575828
TI  - Incidence of pregnancy-induced hypertension among gestational diabetics.
AB  - Although hypertensive disorders of pregnancy are more likely to occur in
      pregestational diabetics, the question of whether they occur more frequently in
      gestational diabetics or certain subsets of gestational diabetics remains
      unclear. This study compared 197 gestational diabetics with 197 control patients
      matched on the basis of age, race, parity, and prepregnancy weight. No
      significant difference was found between the two groups in the incidence of
      either pregnancy-induced hypertension or preeclampsia. There was, however, a
      small but significant elevation in mean arterial blood pressure in the third
      trimester in gestational diabetics compared with control patients (90.1 versus
      87.5 mm Hg; p = 0.006). Mean arterial pressures were also higher in diabetic
      patients on insulin compared with those on diet, and higher in diabetic patients
      diagnosed early (less than 24 weeks) compared with those diagnosed late (more
      than 24 weeks) in pregnancy; however, there were larger numbers of chronic
      hypertensives in these two groups. We conclude that gestational diabetics do not
      develop pregnancy-induced hypertension more frequently. Small increases in blood
      pressure late in pregnancy in these patients achieve statistical significance,
      but their clinical relevance is unclear.

PMID- 7575829
TI  - Perinatal features of pregnancies complicated by nuchal cord.
AB  - The perinatal data of 550 fetuses with a nuchal cord at delivery were compared
      with those of a control group matched for gestational age, maternal age, and
      parity. The study group was subsequently subdivided into those fetuses with
      either single or multiple coils of nuchal cord. No significant differences were
      found in the comparison of routine ultrasound data between the two groups. The
      perinatal mortality rate and the prevalence of arterial pH less than 7.16, venous
      pH less than 7.20, and Apgar scores less than 7 at 5 and 10 minutes were similar
      in both groups. There was a significantly higher incidence of Apgar score less
      than 7 at 1 minute, meconium-stained amniotic fluid, emergency cesarean section,
      need for neonatal resuscitation, and of admission to the neonatal intensive care
      unit in the nuchal cord group compared with the controls. Multiple looping of the
      umbilical cord around the fetal neck was the main factor accounting for the
      higher incidence of these complications and the only explanation put forward for
      the three perinatal deaths that occurred in this group, all of whom presented in
      the preceding week with decreased fetal movements. The results of the present
      study suggest that sonographic identification of nuchal cord may be an important
      observation during third trimester sonography, particularly when evaluating cases
      of decreased fetal movements.

PMID- 7575825
TI  - Continuous fetal heart rate monitoring during bone marrow harvesting in
      pregnancy.
AB  - To date, our computer-assisted search failed to report any case involving a
      gravid patient donating her bone marrow for harvesting. It is known that bone
      marrow harvesting causes a significant decrease in the donor's blood volume and
      therefore this can be potentially detrimental to both the mother and the fetus.
      We report the first case of the gravid donor in which fetal heart rate (FHR)
      during bone marrow harvesting has been studied. Decreased beat to beat
      variability and disappearance of accelerations were noted. The FHR returned to
      normal shortly after the procedure was terminated.

PMID- 7575830
TI  - Effect of magnesium on fetal heart rate variability using computer analysis.
AB  - We studied 16 women, at 32 weeks' or more gestation who required magnesium
      sulfate (MgSO4) therapy for preterm labor or preeclampsia. A 60-minute Doppler
      fetal heart rate (FHR) tracing, analyzed by the Oxford Sonicaid System 8000, was
      obtained for 1 hour before and 2 hours after each patient received intravenous
      MgSO4 therapy. Maternal serum Mg2+ levels were obtained at the second monitoring
      session. Matched paired measures of FHR parameters were compared with the
      Student's t test. After MgSO4 administration, we noted significant falls in long
      term variability, short-term variability, and total acceleration (more than 10
      beats/min) counts. Reduced short-term and overall variability occurred in all
      cases with maternal serum Mg2+ levels more than 4.6 mg/dL. Therapeutic maternal
      serum Mg2+ levels are linked with decreases in long-term and short-term FHR
      variability and acceleration counts. These findings should be considered when
      evaluating resting FHR baseline of patients thus treated.

PMID- 7575832
TI  - Pressor response to cycle ergometry in the midtrimester of pregnancy: can it
      predict preeclampsia?
AB  - Ninety-seven primigravid patients were prospectively studied to assess the
      predictive value of the pressor response to aerobic exercise as a screening test
      for preeclampsia. The blood pressure response to cycle ergometry exercise to a
      maternal pulse of 140 beats/min was recorded on each subject. Each subject was
      studied in the second trimester of pregnancy at a mean gestational age of 23
      weeks (range, 18 to 27). Three of the study subjects developed hypertension with
      proteinuria in the third trimester. A rise in systolic blood pressure of at least
      30 mm Hg occurred in 29 patients, but this did not predict third trimester
      preeclampsia (p = 0.21). A rise in diastolic blood pressure of 20 mm was observed
      in 18 patients, two of whom developed preeclampsia (p = 0.08). An increase of
      diastolic pressure of 20 mm Hg with moderate cycle ergometry exercise in the
      second trimester may predict a subset of patients at elevated risk of
      preeclampsia in the third trimester. However, the positive predictive value of
      this 20 mm Hg pressor increase (11%) limits its applicability as a screening
      test. Thus, we cannot recommend the use of an exercise screening test at this
      time.

PMID- 7575831
TI  - Course of Crohn's disease during pregnancy and its effect on pregnancy outcome: a
      retrospective review.
AB  - The purpose of our study was to review the effects of Crohn's disease on
      pregnancy outcomes. Over a 6-year period, we identified 17 women with pregnancies
      complicated by Crohn's disease. The mean age of the women was 26 years, with a
      mean age of diagnosis at 17 years. Crohn's disease worsened only slightly during
      the pregnancy. Exacerbations of diarrhea were the main problems. Weight gain,
      unadjusted for gestational age at delivery, was 18 pounds. Three babies had low
      birthweight; two were both premature and growth retarded. One woman with active
      disease and no prenatal care had a fetal death at 30 weeks' gestation with
      subsequent disseminated intravascular coagulation. Among women with active
      perianal disease, one was delivered vaginally without exacerbation of symptoms.
      Four women with histories of perianal disease had prophylactic primary elective
      cesarean sections to avoid worsening of symptoms. Three of these women developed
      recurrent perianal disease despite the abdominal delivery. One of these developed
      an abdominal fistula trait in the wound. Our findings suggest that active disease
      at the onset of pregnancy tends to remain active, and quiescent disease tends to
      remain quiescent. Mode of delivery in our series was not protective against
      perineal disease. Although our series is small, it suggests that delivery may
      occur vaginally, with operative delivery reserved for obstetric indications.

PMID- 7575834
TI  - Reversible steroid-induced hypertrophic cardiomyopathy with left ventricular
      outflow tract obstruction in two newborns.
AB  - Dexamethasone is now frequently used in the treatment of bronchopulmonary
      dysplasia. We report on two premature babies receiving dexamethasone who
      developed symptomatic myocardial hypertrophy and left ventricular outflow tract
      obstruction, as documented by M-mode echocardiography and Doppler studies. A
      normal heart was recorded on echocardiography before and after dexamethasone
      treatment. The patients had no known risk factors associated with the development
      of obstructive hypertrophic cardiomyopathy.

PMID- 7575833
TI  - Prenatal diagnosis of intracranial hemorrhage secondary to maternal idiopathic
      thrombocytopenic purpura: a case report.
AB  - We describe a case of a fetus who developed intracranial hemorrhage at the
      beginning of the third trimester of the pregnancy, possibly secondary to maternal
      idiopathic thrombocytopenic purpura (ITP). To our knowledge, this is the first
      reported case of prenatal diagnosis of fetal intracranial hemorrhage occurring in
      association with maternal ITP. The intracranial hemorrhage was intra- and
      periventricular, with the development of posthemorrhagic hydrocephalus. Cesarean
      section was performed at 37 weeks of gestation. The mother did well but the
      newborn died 2 months later. The problem of ITP of the mother in relation to
      pregnancy and the effects on the fetus and the infant are discussed.

PMID- 7575835
TI  - Effect of body position on the blood gases and ventilation volume of infants with
      chronic lung disease before and after feeding.
AB  - The effect of body position before and after tube feeding was evaluated in six
      extremely immature infants who were being mechanically ventilated because of
      chronic lung disease. Their mean birthweight and gestational age were 722.7 g
      (range, 540 to 994) and 24.9 weeks (range, 23.9 to 26.0), respectively. This
      study was performed at a mean postnatal age of 47.5 days (range, 21 to 85 days).
      The prone position resulted in a significant increase in arterial oxygen
      saturation before and after feeding, whereas the tidal volume demonstrated an
      increase only before feeding. Also the prone position showed a significant
      decrease in heart rate before and after feeding and a tendency to decrease
      transcutaneous carbon dioxide tension values before feeding. There were no
      significant differences in minute ventilation despite increased tidal volume in
      the prone position, most likely due to a decrement of the spontaneous respiratory
      rate in the prone positioning. We conclude that the prone position may offer an
      advantage over the supine position in the management of extremely immature
      infants with chronic lung disease before and after feeding.

PMID- 7575837
TI  - Maternal and fetal responses to low-impact aerobic dance.
AB  - The purpose of this study was to compare the physiologic responses to low-impact
      aerobics using treadmill walking as a control. Ten pregnant women between 21 and
      28 weeks of gestation completed 40 minutes of low-impact aerobic dance. The
      maternal and fetal responses were then compared to 40 minutes of walking at the
      same heart rate. The aerobics program consisted of a 10-minute warm-up, 20
      minutes of high-intensity exercise, and 10 minutes of decreasing intensity. Heart
      rates were recorded every 5 minutes, and oxygen uptake (VO2) and fetal response
      (real-time ultrasound) were obtained every 10 minutes. The maternal heart rates
      were similar during both trials (overall, 133 +/- 6 beat/min). VO2 values during
      walking were about 4 mL/kg/min greater than during aerobic dance (p < or =
      0.003). Minute ventilation (VE) was also greater during walking (28.7 +/- 6.4
      versus 24.1 +/- 3.4 L/min, p < or = 0.001). Respiratory exchange ratios and the
      ventilatory equivalents for oxygen (VE/VO2) were similar for both trials. Aerobic
      dance caused greater fetal heart rates than walking (p < or = 0.001), differences
      being as high as 25 beat/min. The fetal rates had returned toward rest within 5
      minutes following exercise. Low-impact aerobic dance, compared with walking at
      similar heart rates, results in a lower maternal metabolic rate and increases the
      transient stress on the fetus.

PMID- 7575836
TI  - Determinants of term intrauterine growth retardation: the Saudi experience.
AB  - In a clinical study from an unselected Saudi obstetric population, the incidence
      of and risk factors for intrauterine growth retardation among live births were
      investigated. From a total study group of 4578 consecutive live births, 76 (1.7%)
      infants were found to be growth retarded. These infants were then compared with a
      randomly selected control group of 76 term newborns with appropriate birthweight
      for their gestational ages. Delivery at term of a growth-retarded infant was
      significantly associated with maternal age under 20 years, maternal body mass
      index less than 23, first degree consanguinity, poor housing, primiparity, and
      inadequate prenatal care in univariate analysis. When considered jointly in
      multivariate logistic regression analysis, the significant determinants were
      reduced to primiparity, first degree consanguinity, and poor housing. These risk
      factors correctly predicted 63% and 71% of the intrauterine growth-retarded
      infants or normal birthweight infants, respectively.

PMID- 7575838
TI  - Relationship between the fetal heart rate pattern and perinatal mortality in
      fetuses with absent end-diastolic velocities of the umbilical artery: a case
      controlled study.
AB  - Fetal decompensation is usually diagnosed by the onset of late decelerations and
      decreased fetal heart rate (FHR) variability and is associated with fetal
      hypoxemia and acidemia and has a high perinatal mortality. Objective analysis of
      the FHR pattern can be performed using the Fischer score and a score of less than
      6 correlates with fetal decompensation. Fetuses with absent end-diastolic
      velocities (AEDV) of the umbilical artery have severe placental disease and
      coupled with this a high perinatal mortality and morbidity. Importantly, AEDV is
      usually observed before the occurrence of fetal decompensation. In fetuses with
      AEDV, delivery before decompensation may improve the perinatal mortality and
      morbidity. To test this hypothesis, the perinatal outcome of fetuses with AEDV
      delivered before decompensation (Fischer score of 6 or more), were compared with
      similar fetuses delivered after decompensation (Fischer score of less than 6).
      All FHR pattern records of fetuses who had AEDV with a birthweight greater than
      750 g and a gestational age of 28 weeks or more were evaluated using Fischer's
      score by a single observer unaware of the perinatal outcome. Fifty-seven fetuses
      qualified for the study and 17 of these babies subsequently died. The babies who
      died had significantly lower mean Fischer scores during the preceding 6 hours
      before delivery (5.9 +/- 1.8 SD) than the survivors (7.7 1.9; p < 0.05), but also
      had lower birthweights and gestational ages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575839
TI  - Is a five-step approach to fetal echocardiography feasible throughout pregnancy?
AB  - The purpose of this study was to determine whether gestational age impacted on
      the length of time required to obtain or identify (not scrutinize) views of the
      fetal heart considered essential for a complete examination. Fetal heart studies
      were performed in pregnancies of 60 patients who were recruited prospectively.
      These patients were placed in three gestational age groups. A 5-step approach to
      fetal echocardiography was formulated for study purposes and included imaging of
      cardiac structures considered essential for a complete examination. Data were
      analyzed by Duncan ANOVA and Pearson correlation coefficient. Among the three
      gestational age groups, there were no significant differences in the length of
      time needed to obtain views that comprised the 5-step approach. In this study the
      time needed to scrutinize each view for normality was excluded. Furthermore,
      there was no correlation between gestational age and the length of time taken to
      obtain all essential cardiac views. The presence of factors cited to be
      hindrances to fetal heart examination was not associated with prolongation of
      time needed to identify essential views of the heart when a 5-step approach was
      utilized throughout pregnancy.

PMID- 7575840
TI  - Tocolysis in advanced preterm labor: impact on neonatal outcome.
AB  - Chart review of 73 patients with 3.5 cm or more dilation, intact membranes, and
      regular contractions at less than 36 weeks. Forty-four (group A) received
      tocolysis with magnesium sulfate, and 13 of the 44 also received indomethacin.
      Twenty-nine (group B) received no tocolysis. Obstetric and neonatal outcomes were
      compared. Demographic factors and admission gestational age, cervical dilation,
      effacement, and uterine activity were similar. Twenty-one of the 44 in group A
      versus 3 of 29 in group B had delivery delayed by more than 48 hours (p = 0.002).
      Group A had a lower incidence of severe respiratory distress syndrome; 4 of 48
      babies in group A versus 9 of 32 in group B (p = 0.04; RR = 0.47; confidence
      interval [CI], 0.2, 1.0). Tocolysis in advanced preterm labor delays delivery by
      more than 48 hours in 50% of patients. The neonatal benefits of aggressive
      tocolysis in cases with advanced cervical dilation may outweigh the potential
      maternal risks of tocolysis, particularly in the setting of extreme prematurity.
      Delay in delivery enabling steroid enhancement of pulmonary maturity reduces the
      severity of respiratory distress syndrome.

PMID- 7575841
TI  - 6-sulfatoxymelatonin levels in pregnant women during workplace and nonworkplace
      stresses: a potential biologic marker of sympathetic activity.
AB  - Melatonin production is regulated by both catecholamines and sympathetic
      activity. Urine levels of the major metabolite of melatonin, 6
      sulfatoxymelatonin, correlate well with serum melatonin levels and have been used
      to evaluate sympathetic output. We tested the hypothesis that urinary levels of 6
      sulfatoxymelatonin would reflect the change in adrenergic activity on working
      days compared with nonworking days during pregnancy. Twenty-three healthy
      pregnant women, employed in a variety of occupations, including physicians,
      nurses, secretaries, salespeople, and laboratory workers were recruited from the
      clinics of the University of North Carolina School of Medicine. We measured 6
      sulfatoxymelatonin levels in first morning voids and for the subsequent 10 hours
      at 24, 28, 32, and 36 weeks' gestation. Urine was collected in sets during
      working days and during nonworking days. 6-Sulfatoxymelatonin was measured by
      radioimmunoassay. In 11 women we also measured urine catecholamines by high
      performance liquid chromatography. Levels of 6-sulfatoxymelatonin output did not
      change across gestation, although they tended to drift down as pregnancy
      progressed. Median levels at first morning void were 6.3 micrograms on workdays
      and 4.6 micrograms on nonworkdays. Although all values were skewed toward work
      being greater than nonwork, there were large interindividual variations. We
      therefore compared subjects against themselves and compared work levels for each
      subject to the corresponding gestational age-matched nonwork value. Among the 23
      women, median 6-sulfatoxymelatonin levels were 81% greater during work than
      nonwork (p < 0.0002) when first morning collections were compared. Daytime
      urinary excretion of 6-sulfatoxymelatonin on workdays was 38% (p < 0.005) greater
      than during nonworkdays.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575842
TI  - Familial infantile olivopontocerebellar atrophy.
AB  - Infantile olivopontocerebellar atrophies are rare progressive, fatal, neurologic
      conditions characterized pathologically by loss of neurons and gliosis in the
      cerebellum, pons, and inferior olivary nuclei in early life. The clinical and
      pathologic features of 2 brothers who presented in early infancy with failure to
      thrive and neurologic deterioration leading to death by the age of 5 months are
      reported. Magnetic resonance imaging of the brain of Patient 1 disclosed
      progressive pontocerebellar atrophy. Both siblings had identical patterns of
      neuronal loss consistent with olivopontocerebellar atrophy at postmortem
      examination. Serum biochemical abnormalities of low thyroid binding globulin,
      hypoalbuminemia, and low cholesterol, suggestive of the carbohydrate-deficient
      glycoprotein syndrome, were also present in both patients.

PMID- 7575843
TI  - Outcome of children with opsoclonus-myoclonus regardless of etiology.
AB  - Within the past 11 years, 11 patients with opsoclonus and myoclonus, with or
      without a history of neuroblastoma, have been admitted to Children's Memorial
      Hospital. Eight of the 11 children had an occult neuroblastoma. Eight children
      have had subsequent delayed development with motor incoordination and speech
      delay (7 with neuroblastoma, 1 without). Nine of 11 children initially were
      treated with ACTH, 1 child was treated with prednisone, and 1 was not treated.
      Nine of the 10 children who were treated had recurrences of symptoms during the
      gradual withdrawal or discontinuation of ACTH. Often the ACTH had to be restarted
      or increased, although several times the episodes were self-limited, not
      requiring treatment after ACTH was withdrawn. We found prednisone was ineffective
      in controlling opsoclonus-myoclonus regardless of etiology. The majority of
      children with opsoclonus-myoclonus, regardless of etiology, have developmental
      delay, more severe and at a higher rate than previously reported. When a
      neuroblastoma was present, tumor removal did not improve symptoms. Although
      limited in size, our study indicates patients with opsoclonus-myoclonus without
      an associated neuroblastoma have a better chance for normal neurologic
      development (2/3 versus 1/8).

PMID- 7575844
TI  - Developmental changes in P300 wave elicited during two different experimental
      conditions.
AB  - Age-related correlations on auditory event-related potentials were studied using
      a task-relevant oddball paradigm in 175 normal subjects aged 4-21 years and age
      related correlations in the "ignore" condition were studied in 108 normal
      subjects aged 1-21 years. In the ignore condition, subjects more than 4 years of
      age were instructed to read a book to divert attention from the auditory
      stimulus. From 4 to about 17 years of age, the latencies of task-relevant P300 in
      event-related potentials (ERPs) gradually shortened. In the ignore condition
      experiment, the P300 latency shortened progressively, but stabilized at about 12
      years of age. Whereas P300 in the ignore condition likely corresponds to P3a
      described previously (passive attention), the conventional P300 wave corresponds
      to P3b (active attention). The findings indicate a developmental difference
      between the P3a and P3b potential.

PMID- 7575845
TI  - Epilepsy in children with meningomyelocele.
AB  - The medical records of 89 children followed at a multidisciplinary
      Meningomyelocele Clinic at the Children's Clinics for Rehabilitative Services
      were reviewed. Almost all children in southern Arizona with meningomyelocele are
      followed at this clinic. Eight children (foreign nationals) were excluded because
      they were not eligible for neurosurgery/neurology services at the clinic. The
      remaining 81 children have been followed at the clinic from 0.25 to 21 years.
      Seventeen children (21%; age: 1.3-17 years, mean: 9.1 +/- 4.4 years; follow-up:
      1.3-16 years) manifested seizures at some time during their course. All children
      with seizures had shunted hydrocephalus. Neonatal seizures occurred in 2 children
      currently not receiving medication. An additional 3 children had an acute
      symptomatic seizure associated with an intraventricular hemorrhage during
      ventriculoperitoneal shunt revision, 2 of whom later developed epilepsy. Fourteen
      children (17.3%) had epilepsy; 12 were taking antiepileptic drugs. Seizures were
      controlled on medication in 5 children. EEG abnormalities were present in 12
      children (focal slowing 4, focal spikes 8, diffuse slowing 3, generalized or
      bilaterally synchronous spike-wave 4). Most of these children (12/14) had
      evidence of additional central nervous system (CNS) pathology (i.e., areas of
      encephalomalacia or past stroke 7, cerebral malformations 2, CNS calcifications
      1, and frequent apneic spells/cardiac arrest 2). We conclude that epilepsy occurs
      in approximately 17% of children with meningomyelocele, and most have other CNS
      pathology to account for their seizures.

PMID- 7575846
TI  - Hyperventilation activation on EEG recording in children with epilepsy.
AB  - In 20 patients with epilepsy, electroencephalography (EEG) slowing was
      quantitatively characterized during standardized hyperventilation activation
      (respiratory rate: 30/min, threefold elevation of total expiratory volume,
      duration: 4 min) and changes in cerebral blood flow and velocity in the right
      common carotid artery were monitored with the Doppler ultrasonic method. Thirteen
      age-matched normal children served as controls. The results were as follows: (1)
      EEG slowing in the epilepsy group was greater compared with controls. (2) There
      was a significant decrease in mean frequency (decrease in alpha power and
      increase in delta power) during hyperventilation in the epilepsy group, but no
      significant change in the controls. (3) The decrease in cerebral blood flow (CBF)
      was greater in the epilepsy group at the beginning of hyperventilation, possibly
      related to the greater EEG slowing. (4) The percentage of CBF at the end of
      hyperventilation was similar in the epilepsy and control groups. The difference
      in EEG response to hyperventilation between the 2 groups may be due to
      differences in the decrease in CBF volume and the sensitivity of the change in
      CBF.

PMID- 7575847
TI  - Ischemic thalamic infarction in children: clinical presentation, etiology, and
      outcome.
AB  - Clinical features of thalamic strokes have not been well delineated in children.
      Six children with ischemic thalamic infarcts (3 M, 3 F; age range: 21 months to
      14 1/2 years) are reported. Three patients had infarction in the thalamoperforate
      artery territory and all had a decreased level of consciousness and hemiparesis;
      two of them also had associated ocular motility abnormalities. One patient with
      left thalamotuberal artery stroke presented with aphasia. Two patients with
      thalamogeniculate artery infarcts had hemiparesis and involvement of the
      posterior cerebral artery. Etiologic factors in our patients were: infectious
      vasculitis, congenital heart disease, migraine, and unknown in 1 patient each and
      trauma in 2 patients. Follow-up information was available for 5, 4 of whom
      recovered completely. One patient was left with a neurologic deficit. We conclude
      that the prognosis of ischemic thalamic strokes in children is relatively good.

PMID- 7575849
TI  - Vogt-Koyanagi-Harada syndrome in a 4-year-old child.
AB  - Vogt-Koyanagi-Harada syndrome is an acquired illness with ocular, cutaneous,
      and/or neurologic features. A 4-year-old child who acutely developed visual
      disturbances and headache and was found to have serous retinal detachments and
      aseptic meningitis is presented. Improvement was rapid with corticosteroid
      therapy. This is the youngest reported patient with Vogt-Koyanagi-Harada
      syndrome.

PMID- 7575848
TI  - SPECT abnormalities in generalized dystonia.
AB  - A patient with severe, generalized dystonia and 6 age range-matched controls were
      studied with the regional cerebral blood flow tracer technetium-99m
      hexamethylpropyleneamine oxime by single-photon emission computed tomography to
      test the hypothesis that cerebellar function is abnormal in dystonia. Analysis
      was performed by drawing regions of interest around the caudate head nuclei,
      hemithalami, deep cerebellar nuclei, and cerebellar hemicortices. The counts in
      each region of interest were normalized to whole brain cerebral blood flow in an
      identical manner for each subject. The dystonic patient had a difference in
      regional cerebral blood flow between the right and left deep cerebellar nuclei,
      increased regional cerebral blood flow in subcortical motor structures, and an
      abnormal relationship between right cerebellar cortical and right deep cerebellar
      nuclear regional cerebral blood flow. The findings in this patient provide
      evidence that the cerebellum may play a role in the pathophysiology of motor
      signs in some patients with dystonia.

PMID- 7575851
TI  - Spontaneous extracranial carotid artery dissection in children.
AB  - Dissection of cerebral arteries as a cause of stroke is rarely recognized in
      children. Two patients with stroke due to extracranial carotid artery dissection
      are reported. A 7-year-old girl with a 2-week history of right arm chorea had a
      left basal ganglia infarct and is receiving haloperidol for persistent chorea.
      The second patient, a 15-year-old boy, developed aphasia and right hemiparesis a
      day before admission during a football game without obvious trauma. He had a
      large left middle cerebral artery infarct and died of cerebral edema and
      herniation. We believe that strokes due to arterial dissection are more common
      than currently recognized, partly because of a lack of history of trauma, and
      suggest that cerebral artery dissection be considered as an etiology of childhood
      strokes. Greater awareness of arterial dissection as a cause of stroke and
      availability of noninvasive techniques like magnetic resonance angiography should
      result in a more accurate diagnosis and improved prognosis in these patients.

PMID- 7575853
TI  - Malignant rhabdoid tumor of the brain and kidney in a child: clinical and
      pathologic features.
AB  - Malignant rhabdoid tumor (MRT) is most frequently found in the kidney, but can
      occur in other tissues including the brain. The simultaneous appearance of MRT in
      the brain and kidney has rarely been described. We report the first fully
      described case of simultaneous appearance of MRT in the kidney and cerebellum of
      an 8-month-old boy. Cytoplasmic inclusion-like masses, representing aggregates of
      intermediate filaments, positively stained by Vimentin and by epithelial membrane
      antigen, were abundant in the kidney tumor but rare in the cerebellar tumor,
      suggesting that this often-described characteristic of kidney MRT can be an
      infrequently observed feature of brain MRT, which consequently may be thought to
      represent another type of tumor.

PMID- 7575852
TI  - Clinical, neurophysiologic, and neuropathological features of an infant with
      brain damage of total asphyxia type (Myers).
AB  - An infant who demonstrated clinical features compatible with total asphyxia is
      reported. Immediately after birth, the patient manifested severe hypotonia and
      total absence of cranial nerve functions. Magnetic resonance imaging revealed
      abnormal intensity of the thalamus and putamen, and atrophy of the brainstem.
      Late components of brainstem auditory evoked potential were absent, but
      electroencephalography was normal. Postmortem autopsy revealed destructive
      lesions of the brainstem tegmentum, thalamus, basal ganglia, and spinal cord, but
      preserved cerebral cortex; findings consistent with those of total asphyxia as
      reported by Myers, and attributable to prenatal insult.

PMID- 7575850
TI  - Renal tubular acidosis complicated with hypokalemic periodic paralysis.
AB  - Three Chinese girls with hypokalemic periodic paralysis secondary to different
      types of renal tubular acidosis are presented. One girl has primary distal renal
      tubular acidosis complicated with nephrocalcinosis. Another has primary Sjogren
      syndrome with distal renal tubular acidosis, which occurs rarely with hypokalemic
      periodic paralysis in children. The third has an isolated proximal renal tubular
      acidosis complicated with multiple organ abnormalities, unilateral carotid artery
      stenosis, respiratory failure, and consciousness disturbance. The diagnostic
      evaluation and emergent and prophylactic treatment for these three types of renal
      tubular acidosis are discussed.

PMID- 7575854
TI  - Mitochondrial DNA deletion in a patient with mitochondrial myopathy, lactic
      acidosis, and stroke-like episodes (MELAS) and Fanconi's syndrome.
AB  - Large-scale mitochondrial DNA deletion was found in a 5-year-old girl with
      mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS) and Fanconi's syndrome. Muscle biopsy disclosed ragged-red fibers and
      cytochrome c oxidase negative fibers. Respiratory chain studies were normal.
      Southern blot analysis demonstrated a 10.5-Kb heteroplasmic deletion in both
      muscle and blood. Deleted genomes represented 40% of total mitochondrial DNA in
      muscle and 63% in blood. There was no evidence of point mutations characteristic
      of MELAS. We suggest that not only patients with progressive external
      ophthalmoplegia syndromes, but also those with defined syndromes [e.g., MELAS or
      myoclonic epilepsy and ragged-red fibers (MERRF)] without characteristic point
      mutations, be screened for mitochondrial DNA deletions.

PMID- 7575855
TI  - Kluver-Bucy syndrome following heat stroke in a 12-year-old girl.
AB  - A 12-year-old girl developed Kluver-Bucy syndrome (KBS) following heat stroke.
      She demonstrated the features typical of human KBS, including visual agnosia,
      hypermetamorphosis, hypersexuality, language disorder with aphasia, hyperorality,
      placidity, flat affect, and memory dysfunction. Magnetic resonance imaging 11 1/2
      months after onset disclosed mild, diffuse atrophy. Fourteen months after onset,
      she did not consistently respond to language or communicate verbally, and was
      dependent on others. A comparison is made with previously reported KBS cases in
      children.

PMID- 7575857
TI  - Early onset bilateral calcifications and epilepsy.
AB  - Bilateral occipital calcifications associated with epilepsy and sometimes with
      celiac disease have been described previously. A boy with bilateral frontal and
      occipital diffuse calcifications accompanied by failure to thrive, nephrogenic
      diabetes insipidus, developmental delay and seizures, but without celiac disease
      is presented. Follow-up at 3 years of age disclosed neurodevelopmental delay,
      height and weight less than expected for age, and seizures controlled with
      carbamazepine. The uncommon association of these features and the early onset of
      symptoms is discussed. Although bilateral occipital calcifications share some
      clinical features with bilateral fronto-occipital calcifications, it is arguable
      whether the two are on a spectrum of a single disease or represent separate
      entities.

PMID- 7575856
TI  - Neonatal segmental myoclonus associated with hyperglycorrhachia.
AB  - Segmental or spinal myoclonus is an uncommon involuntary movement in infancy
      which has been attributed to sepsis, degenerative and developmental diseases of
      the spinal cord, birth trauma, and sclerosing panencephalitis. A premature infant
      presenting with segmental myoclonus associated with extreme hyperglycorrhachia
      secondary to the administration of parenteral nutrition through a femoral
      percutaneous indwelling central catheter that had inadvertently migrated into a
      paravertebral vein is reported. We recommend a lateral abdominal radiograph in
      addition to the usual anteroposterior view to confirm the correct placement of
      femoral catheters.

PMID- 7575859
TI  - Congenital myotonic dystrophy.

PMID- 7575858
TI  - Rhabdomyolysis due to hereditary torsion dystonia.
AB  - Following an acute dystonic crisis, a 6-year-old boy with hereditary torsion
      dystonia developed rhabdomyolysis. To our knowledge, hereditary torsion dystonia
      has never been reported as a cause of rhabdomyolysis. Early diagnosis and
      treatment of rhabdomyolysis should be considered in children with severe dystonia
      in order to prevent renal failure.

PMID- 7575860
TI  - Pica and olfactory craving of pregnancy: how deep are the secrets?
AB  - The practice of pica during pregnancy is described in contemporary literature as
      the ingestion of nonfood substances and food staples in response to craving. A
      previously unnamed practice, olfactory craving of pregnancy, is the smelling by
      pregnant women of selected substances in response to craving, which may occur
      alone or with pica. Observations and descriptions of women's experiences of pica
      and olfactory craving were documented during individualized postpartum bedside
      instruction of 300 women at a midwestern hospital between 1992 and 1994. Most
      women were African American and low income. Eight themes about pica of pregnancy
      were keeping practices secret, singularity of the experience, obtaining the
      craved substance, fears for effects on the fetus, yielding or not yielding to
      cravings, use of substances as medication, pica and food intake, and sensory
      experiences other than taste. Three themes about olfactory craving of pregnancy
      were changes in sense of smell during pregnancy, types of craved substances and
      settings, and escalation in use during pregnancy. The clinical stages of pica and
      olfactory craving require further investigation, and perinatal caregivers have to
      seek and remove the barriers that cause pregnant women to isolate themselves with
      the practices that stem from these cravings.

PMID- 7575861
TI  - Evaluation of antenatal and postnatal support to overcome postnatal depression: a
      randomized, controlled trial.
AB  - This randomized, controlled trial tested the hypothesis that women identified as
      more vulnerable to developing postnatal depression who attended two specific
      antenatal groups and one postnatal group have a reduced frequency of postnatal
      depression from 37 to 15 percent at 6 weeks, 12 weeks, and 6 months postpartum. A
      modified antenatal screening questionnaire was completed, and women identified as
      more vulnerable to postnatal depression were stratified by parity and randomly
      allocated to receive extra support groups or to a control group. The Edinburgh
      Postnatal Depression Scale (EPDS) was used to detect postnatal depression.
      Attendance at the support groups was low, 31 percent overall. At six weeks, in
      the intervention group, 8 (13%) of 64 women scored high (> 12) on the EPDS,
      compared with 11 (17%) controls. Similarly, at 12 weeks 7 (11%) of 63 versus 10
      (15%) of 65 women scored higher than 12, and at 6 months, 9 (15%) of 60 versus 6
      (10%) of 64 women scored higher than 12, indicating that the intervention did not
      reduce postnatal depression. It is possible that the method of applying the
      intervention, using groups separate from the standard antenatal classes, may have
      affected attendance. More research is required into ways of reaching and
      supporting women who may become depressed.

PMID- 7575863
TI  - Does a twin pregnancy have a greater impact on physical and emotional well-being
      than a singleton pregnancy?
AB  - A prospective, population-based study was conducted to assess the impact of twin
      pregnancy on a woman's physical and emotional well-being. It compared women's
      reports of their general health, experience of a range of specific symptoms, and
      emotional well-being during pregnancy using the Edinburgh Postnatal Depression
      Scale. The subjects were 147 women expecting twins and 11,061 women expecting a
      single child who completed questionnaires at both 20 and 32 weeks' gestation as
      part of the Avon Longitudinal Study of Pregnancy and Childhood. Results suggested
      that women expecting twins experienced poorer physical well-being but not poorer
      emotional well-being than those expecting a single child, even though a
      significant association between poor health and emotional well-being was found
      for the population as a whole. It was suggested that the transitory nature of a
      twin pregnancy, the "special" status of a twin pregnancy, greater social support,
      and modified expectations about health may buffer the effects of poor physical
      health on emotional well-being in a twin pregnancy. The findings should alert
      those who care for women expecting twins to the greater physical stress these
      women may feel.

PMID- 7575862
TI  - Decreased cesarean birth rates and improved perinatal outcome: a seven-year
      study.
AB  - This study examined the decrease in cesarean section rates in relation to
      perinatal mortality between 1987 and 1993 at the primary referral hospital in
      north Jordan. Most of the population is at high risk and of low socioeconomic
      status. The cesarean section rate decreased from 15.5 percent in 1987 to 8.7
      percent in 1993, and has remained at this low rate. During the same period the
      perinatal mortality dropped from 52 to 20.9 deaths per 1000 live births. These
      results do not include perinatal morbidity. The successful reduction of the
      cesarean section rate is attributed to active management of labor, trial of labor
      for women with a previous cesarean birth, and vaginal breech delivery in selected
      women. We conclude that the rate of cesarean delivery can be safely reduced in a
      developing country without adverse effects on birth outcomes.

PMID- 7575864
TI  - Do childbirth classes influence decision making about labor and postpartum
      issues?
AB  - This study investigated the role of childbirth education for women attending the
      Royal Women's Hospital Family Birth Center, Melbourne, Australia, in relation to
      making decisions about breastfeeding, pain medication, and length of hospital
      stay. Fifty-nine primiparous women completed a questionnaire after delivery about
      the influence of childbirth education classes on their decisions during
      pregnancy, birth, and the postnatal period. The results indicated that although
      the women enjoyed childbirth education classes, the information they received had
      minimal effect on their decision to breastfeed and the appropriateness of a 24
      hour stay. Information gained about the use of pain medication in labor was
      clearly helpful when women made decisions about pain relief. Educational
      strategies have failed to address the tendency of nulliparous women to postpone
      making decisions about the postnatal period such as early discharge, and further
      investigation on this aspect of a childbirth education program is suggested.

PMID- 7575865
TI  - Reducing pain and enhancing progress in labor: a guide to nonpharmacologic
      methods for maternity caregivers.
AB  - Many simple, effective, low-cost methods to relieve labor pain can be initiated
      by nurses, midwives, or physicians with the potential benefits of improved labor
      progress, reduction in use of riskier medications, patient satisfaction, and
      lower costs. These nonpharmacologic methods are categorized by the mechanisms
      through which they reduce pain or improve labor progress: diminishing the painful
      stimulus at the source; providing alternate stimuli to inhibit pain awareness;
      and reducing the woman's negative reaction to the pain. This is a review of
      numerous pain relief techniques and a guide for maternity caregivers.

PMID- 7575866
TI  - Sheila Kitzinger's letter from England: is water birth dangerous?

PMID- 7575867
TI  - How do newborns find their mother's breast?

PMID- 7575869
TI  - Autogenous replacement of the meniscus cartilage: analysis of results and
      mechanisms of failure.
AB  - Autogenous replantation of meniscal cartilage (resection of 80% of the meniscus
      cartilage followed by immediate replantation) was performed in 14 dogs as a
      control arm of a meniscal replacement study. The purpose was to assess the
      ability of the excised tissue to heal to the intact rim and function as a
      meniscus cartilage. This procedure is an idealized model of allografting meniscus
      cartilage in that the tissue is fresh, autogenous, and perfectly sized. If this
      procedure did not succeed, it seemed likely to the authors that allografting
      meniscal cartilage would have diminished chances for success. Evaluation of these
      replant failures led us to speculate that the causes and mechanisms might include
      slow or incomplete revascularization, inadequate mechanical fixation or
      stabilization, and, perhaps, some type of rejection phenomenon not examined or
      confirmed in the present study. We believe these mechanisms will be particularly
      deleterious for allografted meniscal cartilages and recommend further extensive
      evaluation of meniscal allografts before wide clinical use.

PMID- 7575868
TI  - Insertion-site anatomy of the human menisci: gross, arthroscopic, and
      topographical anatomy as a basis for meniscal transplantation.
AB  - A cadaveric study was performed to determine the insertion-site anatomy of the
      human menisci, their topographical relationships to adjacent intra-articular
      structures, and which arthroscopic portal provides for optimal visualization of
      each insertion site. Fifteen fresh-frozen cadaver knees were studied (ages 48 to
      63 years). Ten knees underwent arthroscopy using four standard arthroscopic
      portals. Visualization and placement of an arthroscopic guide over each meniscal
      horn insertion site was attempted through the four arthroscopic portals. Guide
      wires were drilled to mark horn insertions followed by a gross dissection to
      evaluate accuracy of the guide wire gross dissection to evaluate accuracy of the
      guide wire placement and to isolate meniscal horn insertion sites. Insertion
      sites were outlined and evaluated for size and topographical relationships to
      other intra-articular structures. Five additional knees were dissected free of
      all soft tissues except the tibial insertions of the meniscal roots and anterior
      cruciate ligament/posterior cruciate ligament. Each tibia was mounted in a jig
      and a digitizing system was used to record coordinates of points along the
      outline of each bony meniscal horn insertion site, the ACL tibial insertion, and
      the articular surface of each tibial plateau. The x, y, z coordinates for each
      point were calculated and loaded into a computer program allowing for surface
      area determination and computer-generated topographical maps to assess relative
      position of each specific insertion site. Placement of the arthroscope in the
      anterolateral portal allows optimal visualization and guide wire placement for
      both lateral meniscal horn insertion sites. Medial meniscal anterior and
      posterior horn insertion sites are best visualized with the arthroscope in the
      anteromedial and posteromedial portals respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7575870
TI  - Deltoid and supraspinatus muscle pressures following various arthroscopic
      shoulder procedures.
AB  - Twenty-four consecutive patients were monitored for pressure elevations in the
      supraspinatus and deltoid muscles following various arthroscopic shoulder
      procedures. All patients had clinically swollen shoulders and mild pressure
      elevations in both muscles immediately following each procedure. Muscle pressure
      elevations seen immediately postoperatively were clinically insignificant, as no
      ill effects were seen at follow-up. The extreme clinical swelling following
      various arthroscopic shoulder procedures appears to be related to the type of
      procedure performed, but more directly to the amount of irrigation fluid
      required.

PMID- 7575871
TI  - Femoral nerve block as an alternative to parenteral narcotics for pain control
      after anterior cruciate ligament reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction is associated with significant
      postoperative pain, usually requiring parenteral narcotics. A prospective study
      of arthroscopically assisted autograft patellar tendon ACLR was initiated using
      Winnie's "three-in-one" femoral nerve block (FNB) as the primary means of
      postoperative pain control. Patient satisfaction and absence of parenteral
      narcotic use indicated clinical success. Of 24 patients studied, 92% had no
      parenteral narcotics administered following FNB. Ninety-five percent of patients
      believed FNB was beneficial and would request another. The average duration of
      pain control was 29 hours and the majority of patients (79%) believed discharge
      was possible within 23 hours. There were two patients who failed to respond to
      FNBs (8%) and no major complications. FNB is a safe, reliable, and effective form
      of analgesia following ACLR, eliminating the need for parenteral narcotics.

PMID- 7575872
TI  - Arthroscopic bioabsorbable tack stabilization of initial anterior shoulder
      dislocations: a preliminary report.
AB  - Twenty-six consecutive cadet athletes sustained an acute, initial anterior
      shoulder dislocation. All dislocations required a manual reduction for initial
      treatment. Arthroscopy was performed within 10 days in all patients. The Beach
      chair position and interscalene anesthesia were used in each case. At
      arthroscopy, 25 patients had an avulsion of the anterior-inferior capsulolabral
      complex (Bankart lesion) from the glenoid rim. One patient had a lateral
      detachment of the inferior glenohumeral ligament from the humeral neck. Twenty
      three patients had a Hill-Sachs lesion and 3 SLAP tears were noted. All Bankart
      lesions were repaired with a cannulated bioabsorbable fixation device. Nineteen
      patients, over 1 year postoperative, are the subject of this preliminary report.
      The average age was 19.5 years (range, 17 to 23 years). Follow-up averaged 19
      months (range, 12 to 24 months). The average loss of external rotation was 3
      degrees. There have been no recurrent dislocations and 1 patient has had a single
      episode of resubluxation. Using the Rowe point score, 16 patients were rated
      excellent, 2 good, and 1 fair. All of the athletes in this study have returned to
      preinjury performance status. Acute stabilization of initial anterior shoulder
      dislocations appears to be an effective treatment option in young athletes known
      to have high recurrence rates with nonoperative treatment. This particular
      technique has been safe with little morbidity.

PMID- 7575873
TI  - Hip arthroscopy: an anatomic study of portal placement and relationship to the
      extra-articular structures.
AB  - The purpose of this study is to accurately describe the relationship of the major
      neurovascular structures to standard portals used in hip arthroscopy. Placement
      of three standard arthroscopic portals was simulated in eight fresh paired
      cadaveric hip specimens by placing Steinmann pins into the joint under
      fluoroscopic control. The specimens were then dissected and the relationship of
      the portals to the following structures was recorded: lateral femoral cutaneous
      nerve, femoral nerve, ascending branch of the lateral circumflex femoral artery,
      superior gluteal nerve, and sciatic nerve. The lateral femoral cutaneous nerve
      had divided into three or more branches at the level of the anterior portal. The
      anterior portal averaged only 0.3 cm from one of these branches. The average
      minimum distance from the anterior portal to the femoral nerve was 3.2 cm. The
      ascending branch of the lateral circumflex femoral artery averaged 3.7 cm from
      the anterior portal. A terminal branch of this vessel was present in three
      specimens 0.3 cm from the portal. The superior gluteal nerve averaged 4.4 cm
      superior to the anterolateral and posterolateral portals. The sciatic nerve
      averaged 2.9 cm from the posterolateral portal. From this study, these portal
      placements appear to be safe. Proper positioning depends on careful attention to
      the topographical anatomy about the hip. Avoidance of the important structures
      depends on proper positioning and proper technique in portal placement.

PMID- 7575874
TI  - Arthroscopic proximal patella realignment and stabilization.
AB  - Treatment of patellofemoral pain is a source of much controversy. This is shown
      by the vast number of surgical procedures used in treatment. This article
      describes an arthroscopic proximal realignment technique to address
      patellafemoral pain and instability. We have used this technique to treat acute
      dislocations with capsular deficits, recurrent dislocations, and subluxations.
      This procedure was developed in 1988 as an alternative treatment to distal
      realignment in a 10-year-old child with recurrent dislocation of the patella. In
      adults, we have used this technique in conjunction with a lateral release and in
      two cases with a distal realignment procedure. Our experience is that low
      technical demand, consistency of results, low morbidity, and cosmesis make this a
      worthwhile technique. We believe that this procedure is a valuable technique
      either alone or in conjunction with other procedures in the treatment of patella
      maltracking and instability.

PMID- 7575875
TI  - Initial failure strength of open and arthroscopic Bankart repairs.
AB  - Surgical repair of recurrent anterior shoulder instability requires secure
      fixation of the separated inferior glenohumeral complex to bone. Many techniques
      of fixation are in use for both arthroscopic and open repair. The specific aim of
      this study was to compare the initial failure strength of eight repair techniques
      using a previously described canine model of Bankart repair. Intact capsule-to
      bone complexes failed at the bony interface at 236 N. Traditional Bankart repair
      failed at 122.1 N (2 sutures) and 74.7 N (1 suture), Acufex TAG rod (Acufex
      Microsurgical, Mansfield, MA) at 143.5 N (2 sutures) and 79.8 N (1 suture),
      transglenoid suture technique (2 sutures) at 166.6 N, Mitek GII (Mitek, Norwood,
      MA) (1 suture) at 96.4 N, Zimmer Statak (Zimmer Inc, Warsaw, IN)(1 suture) at
      95.2 N, and Acufex bioasbsorpable Suretac at 82.2 N. The two-suture repairs were
      statistically equivalent in strength to each other, as were the one-suture
      repairs and the Suretac device. Two-suture repairs were significantly stronger
      than the one-suture repairs (P < .01) failure. In the single-suture specimens,
      failure occurred by suture breakage in 46% (18 of 39) of specimens and soft
      tissue failure around the suture in 54% (21 of 39). Failure in the two-suture
      techniques primarily occurred by soft-tissue failure (23 of 25) and this proved a
      statistically significant difference (P < .003). No device broke or pulled out of
      bone.

PMID- 7575876
TI  - Arthroscopic debridement for the osteoarthritic ankle.
AB  - We were able to review 27 out of 32 patients who had arthroscopic debridement for
      osteoarthritis of the ankle. The patients had symptoms for an average of 4 years
      before the procedure. The average follow up was 45 months. Following arthroscopic
      debridement, 17 of the 27 patients showed improvement, although only 2 ankles
      were restored to normal function. There was a statistically significant
      improvement in pain, swelling, stiffness, limp, and activity level. Changes in
      the feeling of instability failed to reach significance. Overall, there were 2
      complications of numbness related to the anterolateral portal, but these
      resolved. Arthroscopic debridement of the ankle can offer relief to approximately
      two thirds of patients, but it is important to stress to patients that the degree
      of improvement is limited.

PMID- 7575877
TI  - Arthroscopic treatment for posterior impingement in degenerative arthritis of the
      elbow.
AB  - Twenty-one patients underwent arthroscopic treatment for posterior impingement
      associated with degenerative elbow arthritis. Anterior debridement and removal of
      loose bodies was performed first. The posterior procedure consisted of three
      parts: removal of posterior loose bodies, removal of the posterior olecranon
      osteophyte, and removal of the osteophytes in the olecranon fossa to the point of
      fenestration. Patients were assessed for pain, strength, motion, stability, and
      function. They were classified as excellent, good, fair, or poor. Twenty-one of
      25 patients were followed an average of 35 months. There was a statistically
      significant improvement in all criteria. There were 10 good and 11 fair ratings
      preoperatively; this improved to 14 excellent and 7 good results postoperatively
      (P = .0001). Arthroscopic treatment for posterior impingement in the degenerative
      elbow offers substantial improvement with minimal risk, provided proper
      intraoperative precautions are followed.

PMID- 7575878
TI  - Hamstring spasm in anterior cruciate ligament injuries.
AB  - The accurate diagnosis of an anterior cruciate ligament (ACL) injury continues to
      be a challenge to clinicians, and often requires magnetic resonance imaging or
      arthroscopy for confirmation. We present a literature review of the currently
      known physical signs of ACL injury, followed by three case reports that describe
      a sign we believe may be helpful in the diagnosis of acute/semi-acute ACL injury:
      involuntary hamstring spasm.

PMID- 7575879
TI  - Arthroscopy of the elbow: anatomy, portal sites, and a description of the
      proximal lateral portal.
AB  - Cadaveric studies were carried out to evaluate the safety and value of the
      standard portals used in elbow arthroscopy. The dissections were performed in 12
      fresh cadaveric specimens. Each portal was assessed in terms of its safety with
      respect to nearby important structures. A proximal lateral portal was evaluated
      and has subsequently been used in 62 patients. A straight posterior
      (transhumeral) portal was also studied. We have found that in arthroscopy of the
      elbow joint, the proximal approaches (proximal medial and proximal lateral), are
      safer than the anteromedial and anterolateral approaches. All areas of the
      anterior compartment can be visualized using these two portals, and we recommend
      that they be the standard anterior portals used in elbow arthroscopy. All of the
      posterior approaches are safe.

PMID- 7575880
TI  - Shoulder arthroscopy and nerve injury: pitfalls and prevention.
AB  - Shoulder arthroscopy has become a very useful diagnostic and therapeutic
      modality. Unfortunately, like many other invasive procedures it can have
      complications. One of the most worrisome complications, for both the patient and
      surgeon, is that of nerve injury. Nerve injury during shoulder arthroscopy is
      often a transient phenomenon although a more severe injury has been documented.
      We review much of the literature on this subject and discuss some of the many
      pitfalls and preventative strategies that have been reported.

PMID- 7575881
TI  - Osteonecrosis of the knee following laser-assisted arthroscopic surgery: a report
      of six cases.
AB  - We report six cases where significant postoperative pain persisted in individuals
      following arthroscopic surgery augmented with the use of lasers. Subsequent
      magnetic resonance images showed lesions with signal changes compatible with the
      diagnosis of osteonecrosis in areas directly addressed with laser energy.

PMID- 7575882
TI  - An unusual intrinsic complication of a patellar tendon allograft and
      recommendations for tissue banking.
AB  - Complications of patellar-tendon allograft for anterior cruciate ligament (ACL)
      reconstruction in ACL-deficient patients have focused on disease transmission,
      strength, survivorship, technique, and processing to decrease antigenicity.
      Little has been described in regard to intrinsic complications of patellar-tendon
      allograft. This article discusses our experience with a damaged patellar-tendon
      allograft that was abnormally long and had a large osseous intratendinous mass.
      Based on this experience, we make recommendations on evaluating and procuring
      patellar-tendon allografts that will help orthopaedic surgeons avoid intrinsic
      patellar-tendon allograft complications.

PMID- 7575883
TI  - Tibial bone plug resorption with extra-articular cyst: a rare complication of
      anterior cruciate ligament reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction failure resulted in tibial bone
      plug resorption and the formation of a large extra-articular cyst. To our
      knowledge, this is the first report of this kind of ACL failure. The relationship
      to known factors is discussed.

PMID- 7575884
TI  - Localized pigmented villonodular synovitis of the posterior compartment of the
      knee: diagnosis with magnetic resonance imaging.
AB  - Localized Pigmented Villonodular Synovitis (LPVS) is a lesion that may affect any
      joint but is frequently found in the knee. Detection and diagnosis of this entity
      are clinically difficult, and plain roentgenograms are usually within normal
      limits. We present a case report of a LPVS localized at the posterior compartment
      of the knee that mimics a meniscal lesion. Magnetic resonance imaging (MRI)
      performed before the resection through an arthroscopic procedure helped to
      diagnose the tumor, which in this case had an infrequent location. MRI is a
      valuable clinical tool for the assessment of intraarticular tumors of the knee
      joint that otherwise may be misdiagnosed and treated as a meniscal tear.

PMID- 7575885
TI  - Subcutaneous pretibial cyst formation associated with anterior cruciate ligament
      allografts: a report of four cases and literature review.
AB  - Four clinical cases are described in which patients who had undergone anterior
      cruciate ligament reconstruction developed ganglion-like cysts at the external
      aparature of the tibial channel. All patients underwent operative treatment
      including curettage and bone grafting with the successful resolution of the
      cysts. A proposal, based on the incomplete incorporation of allograft tissues
      within bone tunnels, is given for the pathogenisis of these cysts, accompanied by
      a detailed description of the relevant literature.

PMID- 7575886
TI  - Arthroscopic repair for a flap tear of the posterior horn of the lateral meniscus
      adjacent to its tibial insertion.
AB  - A flap tear of the posterior horn of the lateral meniscus adjacent to its tibial
      insertion combined with acute rupture of the anterior cruciate ligament was
      successfully repaired arthroscopically by a combination of advancement of the tip
      of the flap into a drill hole created in the tibia and an inside-out stacked
      suture technique using Henning instrumentation in two cases. However, the long
      term function of the repaired menisci, which was reduced several millimeters in
      circumferential length, is still unknown.

PMID- 7575888
TI  - An unusual surgical emergency: a knee joint wound caused by a needlefish.
AB  - The authors report the case of a knee joint wound caused by a needlefish of the
      Belonid type, or "Orphie." This observation is one of a series of 10 traumas
      reported over the past few years with this dangerous fish that resides in the New
      Caledonian lagoon. The authors show the importance of a thorough clinical
      examination of the patient and, more especially, the importance of the
      radiological opacity of the foreign body, which is essential for diagnosis. Our
      experience with this type of wound in articular disorders leads us to recommend
      arthroscopic treatment combined with intraoperative radiological control. This
      method is to assure the total exeresis of the foreign body whose sepsis would
      irremediably cause serious acute arthritis.

PMID- 7575887
TI  - Tibial eminence fracture with meniscal entrapment.
AB  - Controversy has existed regarding the treatment of tibial eminence fractures in
      children. It has been widely assumed that closed manipulation of the knee
      resulting in radiographic reduction of the fragment is acceptable. We present a
      case report of a trapped medial meniscus, even after apparent successful closed
      reduction of an incompletely displaced tibial eminence fracture. The integrity of
      meniscii cannot be inferred radiographically. Arthroscopic evaluation allows
      reduction of a trapped meniscus and suture fixation of the fragment is easily
      accomplished.

PMID- 7575889
TI  - Arthroscopically assisted tibial plateau fracture management: a modified method.
AB  - We present a new technique for arthroscopically assisted treatment of tibial
      plateau fracture. This is a modification of previously described reduction and
      grafting techniques. We performed a core graft under the depressed fragment and
      used it for reduction. With the aid of anterior cruciate ligament surgery
      techniques, we aimed to simplify the graft harvesting and reduction for better
      healing.

PMID- 7575890
TI  - Endoscopic anterior cruciate ligament reconstruction: a modified technique for
      graft passage.

PMID- 7575891
TI  - The arthroscopic knot technique for fracture of the tibia in children.

PMID- 7575892
TI  - Delayed hypersensitivity rash to the knee after injection of arthroscopy portals
      with bupivacine (Marcaine)

PMID- 7575893
TI  - Anterior cruciate ligament reconstruction: endoscopic versus two-incision
      technique.

PMID- 7575894
TI  - Effect of cold therapy following anterior cruciate ligament reconstructive
      surgery.

PMID- 7575895
TI  - Deadman theory.

PMID- 7575896
TI  - [Modern aspects of tympanoplasty. An overview].
AB  - The cholesteatoma should be removed with a canal wall down-technique in small
      mastoids. In patients with well or highly pneumatized temporal bones the
      reconstruction of the posterior canal wall is recommended after complete removal
      of the matrix. Myringoplasty is mainly performed using perichondrium. In highly
      damaged middle ears the cartilage palisade technique is indicated. The
      reconstruction of the ossicular chain performed using modern artificial
      materials.

PMID- 7575898
TI  - [Distortion product otoacoustic emissions (DPOAE) in chronic noise-induced
      hearing loss--recommendations for expert assessment].
AB  - The German guidelines for evaluation of chronic noise-induced hearing loss (NHL)
      require two special auditory tests besides pure tone and speech audiometry tests
      as proof of damage to the organum spirale. This requirement is the subject of
      controversy because of the subjective nature of the tests as well as the
      secondary ascending degeneration of neurons in cases of long-term NIHL. The
      application of otoacoustic emissions (OAE) could be a new starting point,
      independent of recruitment. DPOAE are preferable to TEOAE because they are
      frequency specific. For this reason, we carried out measurements of DPOAE in
      addition to the required tests on 33 patients (= 66 ears). The results are
      collected in four groups according to the pure-tone audiogram: a) slight b)
      typical, c) severe, d) no NIHL. The respective DP-Gram curves had typical
      features similar to the course of the pure-tone audiogram. The following
      conclusions are possible: a) in the frequency range up to 1 kHz, ambient noise
      often causes interference to the DP, b) in the frequency range from 1 kHz to the
      frequency of the steep pure-tone threshold decay clear DP amplitudes are seen, c)
      from a inner ear caused hearing loss of appr. 50 dB no DP are detectable, d) DP
      amplitudes are approximately inversely proportional to hearing loss, e) in severe
      NIHL (group C) or even slight conductive hearing loss (group D) no DP are found.
      Based on these results, we recommend including DPOAE as a further differential
      diagnostic test in the evaluation of NIHL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575899
TI  - [Specificity and sensitivity of transient click-evoked otoacoustic emissions
      (TEOAE)].
AB  - Transient click evoked otoacoustic emissions (TEOAE) have been shown to be a good
      test of hearing impairment especially when used for infant screening. However,
      occasional cases of false positive results--TEOAEs in spite of severe hearing
      loss--have been reported. This study encompasses 243 children whose hearing
      thresholds were known from subjective hearing tests and--in questionable cases-
      derived from additional auditory evoked potentials. The TEOAEs proved to have a
      high sensitivity (93%) and a reasonable specificity (67%), if the margin between
      good and bad hearing was set at 30 dB. However, four ears showed good TEOAEs in
      spite of poor hearing thresholds. In three cases, the children proved to have a
      central auditory hearing loss due to a cerebral disorder. One child with
      bilaterally superb TEOAEs had a unilateral deafness of unclear origin with no
      obvious retrocochlear or central disorder. Possible explanations under discussion
      included the presence of a retrocochlear lesion which was too small to show up in
      the tests used or that the defect was located just between the outer hair cells
      and the first neuron, for example in the inner hair cells. Additionally, efferent
      inhibition might cause a functional deafness as described by Rajan (1989) for the
      guinea pig. The results also show that TEOAEs should always be used in the
      differential diagnosis of hearing impairment in generally disabled children. The
      need for hearing aids and especially their adjustment has to be discussed in case
      of good TEOAEs, i.e., normal peripheral hearing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575897
TI  - [Infusion therapy in sudden deafness. Reducing the risk of pruritus after
      hydroxyethyl starch and maintaining therapeutic success--a prospective randomized
      study].
AB  - A Prospective Randomized Study: The aim of the study was to demonstrate the
      effectiveness of two different treatment schemes with hydroxyethyl starch (HES)
      and the incidence of pruritus as a side effect in a population of patients with
      sudden sensorineural hearing loss and hematocrit values above 44% and/or
      hemoglobin values above 14 g/dl. Under these circumstances we found a significant
      hearing improvement with infusions of 500 ml 10% HES 200/0.5 compared to saline
      infusions in a previous double-blind placebo-controlled study. Two groups are
      compared in a prospective randomized study. Group 1 was treated with infusions of
      250 ml 10% HES 200/0.5 and group 2 with 500 ml of the same substance (n = 200).
      No difference in hearing improvement was detected between the two groups. The
      results were significantly better than with saline infusions. Eleven percent of
      the patients in group 1 developed pruritus and 38% in group 2. The incidence of
      pruritus correlated with the cumulative dosage of HES given. A correlation
      between allergic disposition and pruritus could not be found. Therefore, we
      suggest infusions with 250 ml 10% HES 200/0.5 per day for patients with sudden
      sensorineural hearing loss and hematocrit values above 44% and/or hemoglobin
      values above 14 g/dl. Indications for a long lasting HES-therapy should be
      restrictive. The effectiveness of HES has not been yet demonstrated in patients
      with lower hemoglobin and hematocrit values.

PMID- 7575901
TI  - [Subjective and objective evaluation of the outcome of rhinoplasty. A
      retrospective study].
AB  - Between 1983 and 1988, 206 patients underwent a septorhinoplasty in the ENT
      Department of the University Hospital Benjamin Franklin in Berlin. The results of
      the operation were analysed by an "objective" evaluation form including
      measurements of cephalometric angles and a "subjective" questionnaire reflecting
      the patient's view. Ninety-nine patients responded to our questionnaire. About
      one third of our patients were foreigners (mostly Turks). Seventy-five percent of
      the results were good in objective as well as subjective terms. Comparison of
      results between the two sexes did not show a significant difference. A relevant
      discrepancy between the objective and the subjective results was seen in the
      foreign patients. The low average age and therefore unrealistically high
      expectations are a possible explanation for this phenomenon. Patients with small
      preoperative deformities also turned out to be less satisfied with the outcome
      even though the objective result was better. While obtaining the objective
      results, we also realized that the nasofrontal angle seems to be of minor
      importance for the facial profile. The nasofacial and the nasolabial angle
      actually seem to be more important for the rhinoplasty and reflect the aesthetic
      correction of the nose better than the nasofrontal angle. It was much more often
      possible to correct the nasofacial and the nasolabial angle, while the
      nasofrontal angle remained uncorrected in many cases. Our retrospective study was
      able to answer the question whether the aesthetic outcome after rhinoplasty can
      be rated objectively.

PMID- 7575900
TI  - [Quantitative evaluation of the Romberg test].
AB  - Simple and economical measuring platforms are available to aid the ENT clinician
      in examining vestibulospinal disorders. The aim of our study was to
      quantitatively interpret Romberg test measurements. Calculating the area between
      the zero line and the curves in sagittal and lateral direction--for the Romberg
      test with closed and open eyes--enables a quantification of body sway. For the
      evaluation of data, we developed a triangular diagram which allows a graphic
      representation and quantifies vestibulospinal reaction at a glance. We assessed a
      group of 80 persons without any symptoms of peripheral or central vestibular
      system disturbance. Selected patients complaining of vestibular disorders are
      helpful in demonstrating the objective and quantitative interpretation of the
      Romberg test, which is often analysed in a more subjective way.

PMID- 7575902
TI  - [Pulsed color laser for treatment of benign, superficial vascular malformations].
AB  - The flash lamp-excited dye laser is ideal for treating benign superficial
      vascular cutaneous lesions. Port-wine stains, telangiectases, spider angiomas, or
      hemangiomas may be treated without pain. If used properly, complications such as
      skin texture changes, hypopigmentation, and scarring are extremely rare. The
      flash lamp-excited dye laser works on the principle of selective
      photothermolysis, which allows selective damage to the target vessel without
      affecting surrounding tissue. Lesions like xanthelasma palpebrarum, keloid scars,
      and warts may also be treated by the flash lamp-excited dye laser. This study
      presents the results of treatment with this laser in our patients.

PMID- 7575903
TI  - [Value of megestrol acetate in treatment of cachexia in head-neck tumors].
AB  - Mortality of 70% of all patients with tumors in the head and neck is linked with
      anorexia and cachexia. Two reasons for cachexia are well known: 1. local disease
      and local therapy preventing oral nutrition and 2. advanced tumors activating
      biochemical pathways of proteolysis, lipolysis, and gluconeogenesis. Five groups
      of substances are now used to treat tumor-induced cachexia: corticosteroids,
      progestational drugs, cyproheptadine, hydrazine sulfate, and anabolic steroids.
      Between 1992 and 1993 we treated 38 patients suffering from cachexia due to
      advanced cancers of the head and neck with 160 mg megestrol acetate per day for
      four months. The increase in body weight was significant after eight weeks. The
      mean increase after full therapy was 4.58 +/- 3.19 kg. Treatment of the five
      women in the series was very successful and all achieved their former body
      weight. Megestrol acetate therapy was best started after assuring enteral
      nutrition. Significant adverse events were loss of libido for the men, headache
      and, rarely, thrombophlebitis. Our first experiences suggest that megestrol
      acetate treatment is useful in cachectic patients with advanced squamous cell
      carcinomas of the head and neck.

PMID- 7575904
TI  - [Serum soluble interleukin 2 receptor in patients with squamous epithelial
      carcinomas of the upper aerodigestive tract].
AB  - BACKGROUND: Several investigations showed increased levels of the soluble
      interleukin-2 receptor (sIL-2 R) in chronic and malignant diseases. A correlation
      between elevated sIL-2 R levels and disease activity or tumor size was observed
      in some patients. At present, there are no studies of sIL-2 R serum levels in
      patients with squamous cell carcinomas of the upper aerodigestive tract. METHODS:
      SIL-2 R levels were measured in sera of 86 patients with squamous cell carcinoma
      of the head and neck and of 25 healthy controls with a sandwich ELISA. RESULTS:
      Significantly elevated serum levels of sIL-2 R were detected in 49 out of 86
      patients (56.9%) with squamous cell carcinoma of the head and neck. The mean
      serum level in the healthy controls was 437 U/ml compared to 895 U/ml in
      carcinoma patients. A correlation was found between tumor size, number of
      metastases and the sIL-2 R level. There was no correlation with histological type
      or tumor localization. DISCUSSION: The physiological role of sIL-2 R is still
      unknown. Elevated levels of sIL-2 could be a sign of activation of the immune
      system. But they also might be involved in causing the disease. The sIL-2 R serum
      levels in patients with squamous cell carcinoma of the head and neck may serve as
      an unspecific indicator for tumor size and dissemination. CONCLUSION:
      Posttherapeutic titer controls could be of prognostic value. Additionally, sIL-2
      R may help to select appropriate patients for an immunotherapy with recombinant
      IL-2.

PMID- 7575905
TI  - [Meniere disease as an autosome dominant hereditary disease].
AB  - Within one year (1993) we found a positive family history in five out of forty
      eight new patients with Meniere's disease, corresponding to a frequency of 10.4%.
      We found between two and seven cases in each of five families. The disease
      followed a dominant autosomal hereditary pattern over two to four generations.
      Audiometric and vestibulometric examination confirmed the diagnosis. Clinical
      emphasis was placed on trigger factors such as infections, physical and
      psychological stress, the autonomic system, and metabolic and endocrinological
      disorders. There was no evidence of a significantly high incidence of any single
      trigger factor. The most important result of this study, which also included
      human leucocyte antigen (HLA) typing, is the fact that HLA A2 was represented in
      90% of patients with positive family history of Meniere's disease and in 75% of
      patients with solitary Meniere's disease in contrast to only 28.9% in the average
      European population. The frequency of HLA B44 was 70% in family-linked Meniere's
      disease and 37.5% in single Meniere's disease. The frequency in the average
      European population is 12.3%. What is even more striking is the combination HLA
      A2 B44, occurring with respective frequencies of 60%, 37%, and 5%. These results
      suggest a multi-factor etiology of Meniere's disease combined with a genetic
      predisposition, which might be caused by mutations on the short arm of chromosome
      6.

PMID- 7575906
TI  - [Esophagomediastinal fistula and recurrent laryngeal nerve paralysis after
      radiotherapy of Hodgkin's disease].
AB  - The case of a female patient 21 years old at the time of diagnosis is reported.
      The patient suffered from stage IV Hodgkin's disease of the nodular sclerotic
      type with head and neck manifestations in cervical lymph nodes and in the
      esophagus. After radiotherapy; she suffered from an esophageal/mediastinal
      fistula and unilateral paralysis of the recurrent laryngeal nerve. Fifteen years
      later, there are no signs of recurrent tumor growth or a secondary neoplasm.
      Dysphonia was ameliorated by speech therapy, and surgery was not necessary.

PMID- 7575908
TI  - [The monochord, its path from Pythagorean musicology to testing the upper
      auditory tone limit. Pictures from the history of otorhinolaryngology,
      represented by instruments of the Ingolstadt German Medical History Museum].
AB  - The monochord consists of a frame with a string or pianowire stretched across it.
      The length of the wire can be varied by a movable bridge. The string or wire is
      plucked, hit, or bowed, producing transverse vibrations. In this mode the number
      of vibrations per second is dependent on the length, tension, and thickness of
      the string. In ancient times, the Pythagoreans used such an instrument to study
      the natural laws underlying musical intervals; in the 19th century it also served
      for various other physical experiments. F. A. Schulze, physicist in Marburg,
      Germany, introduced the monochord for testing the upper tone limit in 1908. He
      produced longitudinal vibrations by rubbing the wire with a piece of felt
      moistened with benzol. The vibrations of this mode are dependent only on the
      length of the wire and the elasticity of the material; they are independent of
      its tension and thickness. H. J. L. Struycken, otologist in Breda, Holland,
      presented an improved type of monochord in 1910 which also allowed testing bone
      conduction. K. L. Schaefer, physiologist in Berlin, modified Struycken's
      instrument in such a way that bowing the wire or hitting it with a small hammer
      also produced transverse vibrations. This enlarged the range of tones in the
      lower region. In this combined version the monochord was an indispensable piece
      of hearing testing equipment before the era of electronic audiometers. The
      technical development and clinical application of the monochord is described in
      detail.

PMID- 7575907
TI  - [Resorbable intracutaneous suture as wound closure in cochlear implant].
AB  - The extended incision in cochlear implantation has to be performed for several
      reasons; therefore the wound closure needs single or continuous suture for the
      skin. The suture removal seems to be traumatic for children. That is why we have
      using an intracutaneous absorbable suture to avoid material removal for more than
      6 months now without any complications in the 35 patients in question.

PMID- 7575909
TI  - Salary inequities and health care costs.

PMID- 7575910
TI  - Retraining non-generalists to provide primary care.

PMID- 7575911
TI  - Fostering residents' research skills.

PMID- 7575912
TI  - Using standardized students to educate preceptors.

PMID- 7575913
TI  - Oath-taking at medical graduation: the right thing at the wrong time.

PMID- 7575914
TI  - Heavy weather ahead for clinical education in restructured academic health care
      systems.

PMID- 7575915
TI  - Cost containment in U.S. health care.
AB  - The author explains why supply factors, particularly the overdevelopment of the
      nation's medical capacity, are more important than demand factors in explaining
      the high use and cost of U.S. health care. Yet such costly care often does not
      translate into better health for Americans. While market forces, especially the
      efficiencies fostered by managed care, may clear some of the excess acute-care
      capacity and foster the use of less-costly generalist physicians, such forces
      favor the strong over the weak. This makes vulnerable those persons without
      health insurance or on Medicaid only, inner-city and rural hospitals, and
      academic medical centers. And when health care is treated as a market product,
      the relationship between doctors and patients is endangered. The author urges
      that the effects of managed care be watched, particularly for possible neglect of
      the underserved and for diminished employment opportunities for all health
      professionals, especially nurses and certain specialists. He thinks it is likely
      that much of the savings that market forces will create will not stay in the
      health care sector (where they could be used to expand services for the
      uninsured, for example) but will go into the business side of health care (e.g.,
      to pay shareholders' dividends). And he stresses that issues of adverse
      selection, risk adjustment, and outcomes measurement will have increasing
      importance to persons with chronic illnesses, who may be neglected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7575916
TI  - Can academic medical centers compete in a managed care system?
AB  - The authors review characteristics of successful group practices, health
      maintenance organizations, and integrated service networks and then identify the
      critical actions that academic medical centers must take in order to compete with
      such service-oriented community providers. Centers must (1) form the clinical
      faculty into a competitive medical group that offers more price-competitive and
      user-friendly services; (2) restructure clinical training to be more relevant to
      the emerging practice situation; and (3) clearly delineate funding streams and
      identify the cross-subsidies taking place in the teaching, research, and patient
      care enterprises. These changes have the potential to strengthen clinical
      training and improve the financial positions of both the faculty and the
      university hospitals. The authors maintain that centers can make these and other
      necessary changes while still providing high-quality care and maintaining their
      educational and research functions; they cite organizations that have succeeded
      in these ways. However, as with all complex, large-scale organizations, public
      and private alike, the major factor limiting centers' ability to make the
      organizational changes required to successfully compete in the new health care
      environment is the lack of political will. It will be very difficult for academic
      medical centers to unite their powerful internal interest groups and take action
      without first experiencing a rather severe external jolt. The challenge for the
      leaders of academic medical centers is to prepare for the managed care jolt so
      that they can then guide their institutions to a new, more competitive position.

PMID- 7575917
TI  - The place of behavioral science in medical education and practice.
AB  - Medicine and medical practice have undergone dramatic changes in the recent past.
      Technological advances have exceeded the norms of social thought (e.g., frozen
      embryos, surrogate motherhood, assisted suicide, and the right to die), and there
      has been a loss of professional control of the provision of medical services
      because of an inability to control the costs of technology and the patterns of
      practice. These and related changes find the profession of medicine, including
      medical education, without the necessary theory and content to adapt. The author
      explains why this situation makes it more necessary than ever to develop and
      upgrade the teaching of behavioral sciences in the medical curriculum, even
      though these disciplines' breadth and comparative lack of definition create
      special problems for the teaching and learning of behavioral concepts and their
      application to medical practice. The behavioral sciences are needed in medicine
      because their role is not that of a technologically defined knowledge area but
      rather that of a process or functional area that mediates between the patient as
      a person and the delivery of medical care. The author presents concepts, a
      diagram, and teaching examples that explain the characteristics of behavioral
      sciences and illustrate the necessity for including them in the curriculum. He
      concludes by urging the leaders of academic medicine to find practical ways to
      transmit an awareness of behavioral sciences' crucial role in patient care so
      that tomorrow's physicians can function more fully in the complex arena of
      clinical reality.

PMID- 7575919
TI  - Communication as an essential part of program and institutional development.
AB  - The Longitudinal Primary Care Program, an innovative curriculum in generalist
      medicine at the University of Illinois at Chicago College of Medicine, has been
      enhanced by a commitment to fostering good communication among all of its
      participants (who include more than 350 students and nearly 300 office-based
      generalist preceptors) and between participants and administrators. The diverse
      and widely scattered group of preceptors is brought together through orientation
      sessions and faculty development workshops that stress precepting skills and
      mentoring. Preceptors are regularly surveyed and the survey data are analyzed to
      help administrators learn how best to recruit and retain these faculty members.
      Students' input comes through surveys, small-group meetings, and their
      participation on committees. Program evaluation data and formal notes from
      committee meetings are promptly compiled and disseminated. Such efforts to
      promote good communication among preceptors, students, program administrators,
      and the medical college have both enhanced the generalist program and encouraged
      other curricular reforms in the college.

PMID- 7575918
TI  - What medical schools and universities can learn from one another.
AB  - Colleges and universities devoted to undergraduate education and non-medical
      graduate education (hereafter called "universities") have much to teach medical
      schools and much to learn from them. Universities and medical schools differ
      significantly in their sources of revenue, cultures of promotion and tenure,
      academic values, and decision-making processes. Yet from the experience of
      universities, medical schools can learn innovative techniques of curriculum
      assessment and teaching, how to handle diversity issues, and ways to expand the
      definition of scholarship. In turn, medical schools can help teach universities
      the importance of fiscal and regulatory accountability, the benefits of
      interdisciplinary efforts, the practical benefits of problem-based learning, and
      techniques for adjusting to rapid change. The authors, all with medical school
      faculty backgrounds, developed the views reported in this article when they were
      Fellows in a leadership training program sponsored by the American Council on
      Education (ACE). They urge their colleagues to reach out beyond their specialties
      and departments and learn from higher education institutions that are grappling
      with problems analogous to those faced by medical schools.

PMID- 7575920
TI  - Managing information in the academic medical center: building an integrated
      information environment.
AB  - The strategic importance of integrated information systems and resources for
      academic medical centers should not be underestimated. Ten years ago, the
      National Library of Medicine in collaboration with the Association of Academic
      Medical Centers initiated the Integrated Advanced Information Management System
      (IAIMS) program to assist academic medical centers in defining a process for
      addressing deficiencies in their information environments. The authors give a
      brief history of the IAIMS program, and they describe both the characteristics of
      an integrated information environment and the technical and organizational
      structures necessary to create such an environment. Strategies some institutions
      have used to implement integrated information systems are also outlined. Finally,
      the authors discuss the role of librarians in integrated information system
      design.

PMID- 7575921
TI  - Happy(?) birthday, Medicare.

PMID- 7575923
TI  - Non-urgent emergency department visits by patients from a resident ambulatory
      care clinic.

PMID- 7575922
TI  - Teaching and learning in ambulatory care settings: a thematic review of the
      literature.
AB  - A thematic review was conducted of the 1980-1994 research literature on teaching
      and learning in ambulatory care settings for both undergraduate and graduate
      medical education. Included in the review were 101 data-based research articles,
      along with other articles containing helpful recommendations for improving
      ambulatory education. The studies suggest that education in ambulatory care
      clinics is characterized by variability, unpredictability, immediacy, and lack of
      continuity. Learners often see a narrow range of patient problems in a single
      clinic and experience limited continuity of care. Few cases are discussed with
      attending physicians and even fewer are examined by them. Case discussions are
      short in duration, involve little teaching, and provide virtually no feedback.
      Excellent teachers are described as physician role models, effective supervisors,
      dynamic teachers, and supportive persons. Rather than block rotations, students
      and residents prefer longitudinal teaching programs, which offer continuity-of
      care experiences with patients and preceptors. Although little can be concluded
      about learning outcomes, the studies indicate that some medical students and
      residents have deficient skills in interviewing, physical examination, and
      management of psychosocial issues. Based on the reviewed studies, the author
      recommends facilitating learning by increasing continuity-of-patient-care
      experiences and contact with faculty members, encouraging collaborative and self
      directed learning, providing faculty development, and strengthening assessment
      and feedback procedures. The author also recommends further research to learn
      about medical specialties other than internal medicine and family medicine, to
      describe the knowledge and reasoning of both teachers and learners, and to assess
      the influences of various educational programs on learning and satisfaction.

PMID- 7575924
TI  - Assessing the psychological types of specialists to assist students in career
      choice.

PMID- 7575925
TI  - Evaluation of a rural-oriented primary care curriculum for internal medicine
      residents.

PMID- 7575926
TI  - Medical students' career indecision and specialty rejection: roads not taken.
AB  - The authors used data from the AAMC Matriculating Student Questionnaire and
      Medical School Graduation Questionnaire to ascertain how closely the specialty or
      subspecialty choices of the 1991 and 1994 graduates of U.S. medical schools
      matched the preferences they had declared when they were matriculated; the extent
      to which these students strongly considered and then rejected choices that arose
      during medical school; and the graduation choices of the substantial number of
      students in both cohorts who were undecided about their careers when they entered
      medical school. Approximately 80% of the graduates in both classes rejected the
      specialty intentions they had declared when they began medical school. However,
      matriculation interests in the generalist specialties--family practice, general
      pediatrics, and general internal medicine--were more enduring for the 1994
      cohort, while interests in the medical, surgical, and support specialties were
      less so. Large percentages of the 1991 and 1994 cohorts were undecided about
      their careers at matriculation (20.8% and 26.2%, respectively), and nearly the
      same proportions remained undecided at graduation. However, more of the graduates
      in the 1994 cohort who had initially been undecided reached decisions favoring
      one of the generalist specialties than was true for the 1991 cohort. Nearly half
      the 1994 graduates had strongly considered and then rejected an alternative to
      their matriculation interest that arose during medical school. Within the
      generalist specialties, both early and later interests in family practice were
      more durable than were those in general pediatrics and general internal medicine:
      for every student who retreated from tentative interest in family practice,
      another student's interest was reinforced or kindled.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7575927
TI  - Bridging the professions: an integrated and interdisciplinary approach to
      teaching health care ethics.
AB  - In 1993, the authors introduced an interdisciplinary course in health care ethics
      at the University of British Columbia. They were motivated by two convictions:
      (1) an interdisciplinary approach to health care decision making is best; and (2)
      every significant health care decision has an ethical component. They wanted to
      encourage students from the various health care disciplines to participate in
      interdisciplinary decision making in their future practices by giving them an
      opportunity to study health care ethics together during their training. The
      authors give detailed descriptions of the objectives, format, curriculum, and
      evaluation of this innovative course in the hope that other educators who may
      want to develop similar courses can learn from their experience.

PMID- 7575928
TI  - Medical education and reform initiatives in Germany.
AB  - The health care systems of highly industrialized countries are being restructured
      in the face of aging populations, economic dislocations, and limited resources.
      They also face reforms to medical education. Despite significant differences in
      their systems, countries can learn from examining the advantages and
      disadvantages of others' approaches to educating medical students. Germany has
      begun to implement various reforms of medical education and medical practice, and
      the unification of East and West Germany has reinforced these reform efforts. The
      author presents background data and information on the number of practicing
      physicians in Germany and their practice settings; the number of medical
      students; admission policies and the curricula of German medical schools; and the
      nature of post-medical school training. He then describes some proposed reforms
      to the medical curriculum, and the experience of the Medical School of Hannover
      in implementing and evaluating some of these changes.

PMID- 7575929
TI  - Creating university hospitals: rationales and realities.
AB  - This article analyzes the reasons given for the founding of three early
      university hospitals: those at the University of Michigan, the University of
      Pennsylvania, and Johns Hopkins University. The hospital at the University of
      Michigan was founded to ensure medical students' access to clinical instruction.
      The University of Pennsylvania's desire to have not only access to but control
      over hospital affairs provided the impetus to build a university hospital. Johns
      Hopkins University, building upon the examples of Michigan and Pennsylvania,
      firmly joined the hospital and medical school and introduced research as a link
      between these institutions. The early histories of these three institutions
      demonstrate how each created a different mission for its university hospital.
      Today, as in the past, university hospitals must choose which of their multiple
      roles to emphasize. The meaning of "university hospital" has always been
      ambiguous, and this ambiguity can provide useful flexibility to institutions
      responding to a changing environment.

PMID- 7575930
TI  - Professional competencies in the changing health care system: physicians' views
      on the importance and adequacy of formal training in medical school.
AB  - PURPOSE: To examine physicians' attitudes toward 16 competencies deemed essential
      to the effective practice of medicine in the changing health care system. METHOD:
      In early 1991 a telephone survey was conducted of 300 physicians from random
      samples selected as representative of the physician population in the continental
      United States. The physicians were categorized as general practitioners, surgery
      specialists, and other specialists, and as belonging to the graduation cohorts of
      1960-1969, 1970-1979, and 1980-1989. The physicians were asked to rate (1) the
      importance of formal undergraduate training in each of 16 competencies and (2)
      the adequacy of their own undergraduate training in the competencies (these
      ratings are reported only for the 87 physicians in the 1980-1989 cohort). The
      competencies were derived from the skills, attitudes, and behaviors defined by
      the Pew Health Professions Commission as necessary for the nation's health care
      practitioners to meet society's evolving health care needs. RESULTS: Fifty
      percent or more of the physicians thought that 12 of the 16 competencies were
      "very important" to include in undergraduate training. Over 75% thought that it
      was "very important" to include the five competencies involving skills
      traditionally valued in medical practice: diagnosis and treatment, effective
      communication with patients, problem solving, lifelong learning, and counseling
      on medical ethics. More than 50% thought that undergraduate training was "very
      important" in some competencies that reflect the changing dynamics of medicine
      and care delivery over the past ten years: health promotion and preventive
      medicine, involvement of patient and family in care, management of large volumes
      of information, appropriate use of technology, working on a team with other
      professionals, and consideration of cost in clinical decision making. In rating
      their own training, over 50% felt well prepared (ratings of "excellent" or
      "good") in the five traditional competencies and, in addition, in their abilities
      to promote health, to manage large volumes of information, to work in teams, to
      understand and respond to diverse cultures, and to expand access to care.
      However, a majority felt that their training was only "fair" or "poor" regarding
      the involvement of patients and their families, evaluation of the appropriateness
      of costly technology, consideration of cost implications in their decision
      making, and understanding and supporting the community's role in health care.
      Forty percent or more felt poorly prepared to work in managed care settings or to
      accommodate increasing external scrutiny. CONCLUSION: The physicians validated
      the traditional strengths of medical schools, but revealed curricular weaknesses
      in the teaching of competencies proposed as important for the emerging health
      care system, especially in the managed care environment.

PMID- 7575932
TI  - A data-generated basis for medical ethics education: categorizing issues
      experienced by students during clinical training.
AB  - PURPOSE: To use issues identified by students in order to establish an experience
      and evidence-based approach to medical ethics education. METHOD: A total of 628
      sophomore and senior students at the State University of New York at Buffalo
      School of Medicine and Biomedical Sciences were asked to identify incidents
      during their clinical training that had raised ethical concerns. The sophomores
      were surveyed during two time periods: 1979-80, and 1991-92 and 1992-93; the
      seniors were surveyed in 1991-92 and 1992-93. Responses were analyzed and
      categorized through content analysis. RESULTS: In all, 249 students (45% of the
      sophomores and 20% of the seniors) responded. The categories of issues identified
      were professional norms, limits of intervention, defensive shielding of
      professional colleagues, respect toward patients, communication, and student
      boundaries (situations where the student feels uncomfortable). The most
      frequently reported incidents reflected the students' perceptions of lapses in
      level of care (under- or over-treatment), communication, respect toward patients,
      and maintenance of professional norms. The seniors and the 1979-80 sophomores
      reported respect toward patients as an issue less often than did the 1991-92 and
      1992-93 sophomores. The seniors most often identified concerns raised over limits
      of intervention and resource allocation. CONCLUSION: The differences between the
      responses of the sophomores and seniors tend to support other research suggesting
      a retardation of moral sensitivity in the course of medical education. It may be
      that clinical teaching and faculty behavior model values at odds with what is
      taught in the classroom. Ethics education should focus on issues relevant to
      students' experience.

PMID- 7575931
TI  - Use of an objective structured clinical examination to determine clinical
      competence.
AB  - PURPOSE: To describe the performance of second-year internal medicine residents
      on an objective structured clinical examination (OSCE) and to analyze the role of
      the OSCE in the evaluation of clinical competence. METHOD: In 1993-94, 51 second
      year residents in an internal medicine training program at the Mayo Clinic
      participated in an OSCE. The OSCE was administered in four sessions, with 12 or
      13 students in each session. The OSCE was composed of nine physical diagnosis
      stations, with two or three test-interpretation stations per session. Student's t
      test and one-way analysis of variance were used to compare scores on the basis of
      the residents' gender, medical school training (international medical graduates
      versus those trained in the United States and Canada), and OSCE session. In
      addition, the residents' scores were correlated with scores on the American Board
      of Internal Medicine's in-training exam (ITE) and with the training program's
      clinical rotation scores (CRSs). RESULTS: The residents' scores were
      significantly higher for test interpretation stations than for physical diagnosis
      stations (p < .0001). There was no significant difference in average scores based
      on gender, medical school training, or OSCE session. The OSCE scores correlated
      with the ITE scores (r = .30) and the CRSs (r = .40). CONCLUSION: The OSCE's
      moderate correlation with the ITE and CRS suggests that the OSCE, which consists
      largely of physical diagnosis stations, may test a component of clinical skills
      not evaluated by the other measures. Thus, the OSCE is an important addition to
      the assessment of clinical competence.

PMID- 7575933
TI  - Knowledge, confidence, and attitudes regarding medical ethics: how do faculty and
      housestaff compare?
AB  - BACKGROUND: It has been suggested that faculty members' inadequate knowledge of
      and unfavorable attitudes toward ethics may present barriers to effective
      education in ethics for house officers. METHOD: To test this hypothesis, the
      authors administered a questionnaire assessing the knowledge, confidence, and
      attitudes regarding ethics of the 73 house officers and 73 full-time faculty
      members in the Department of Medicine at the Georgetown University Medical Center
      in 1992-93. Statistical analysis of the responses was performed using chi-square,
      two-tailed t-tests, and linear regression. RESULTS: Fifty-five house officers
      (75%) and 57 faculty (78%) responded. The knowledge scores were similarly low for
      both groups (53% correct for the faculty and 50% for the house officers).
      However, the faculty were significantly more confident than the house officers
      regarding ability to address ethical issues (mean ratings of 3.9 vs 3.4 on a
      scale from 1, very low, to 5, very high; p = .0001). Seventy-five percent of the
      faculty and 65% of the house officers believed that ethics training should be
      mandatory during residency. CONCLUSION: The attitudes of the faculty per se do
      not appear to represent a barrier to teaching ethics. However, the gap between
      the faculty members' confidence and knowledge could interfere with their
      abilities to model and teach ethics to house officers.

PMID- 7575934
TI  - The adequacy of medical ethics education in a pediatrics training program.
AB  - PURPOSE: To identify ethical dilemmas commonly encountered during pediatrics
      training as a step toward improving medical ethics curricula for residents.
      METHOD: The authors identified seven recurring topics by reviewing the required
      case reports on ethical dilemmas experienced by students in the third-year
      pediatrics clerkship from June 1992 to June 1994 at the State University of New
      York at Buffalo School of Medicine and Biomedical Sciences. Based on the topics
      identified, the authors then surveyed pediatrics housestaff in 1993-94 regarding
      the frequency of encountering the topics, levels of comfort in addressing the
      topics, role models and resources, and perceived need for improved training.
      RESULTS: A total of 214 student essays were reviewed. Thirty-six of 50 residents
      responded to the survey. In the following list of the seven topics, percentages
      are given for students who reported the topic, for residents who encountered the
      topic "very frequently" or "sometimes," and for residents who felt "very
      comfortable" or "somewhat comfortable" addressing the topic: child abuse or
      neglect (students reported, 28%, residents encountered, 94%, residents felt
      comfortable, 86%); use of heroic measures to maintain a terminal patient (20%,
      89%, 69%); patient confidentiality (19%, 81%, 92%); resource allocation (12%,
      67%, 54%); surrogate decision making (7%, 69%, 75%); patient autonomy (4%, 86%,
      69%); and disclosure of information (2%, 69%, 60%). Eighty percent of the
      residents felt they could not intervene when they disagreed with decisions; 69%
      felt their training had not prepared them to address ethical dilemmas; 69%
      thought attending physicians were interested in discussing ethical issues; and
      74% desired more training. CONCLUSION: Based on their self-reported experiences
      with topics identified as occurring frequently in pediatrics training, the
      residents perceived their training to be inadequate and desired more ethics
      education, but felt that the faculty were willing to assist in that training.

PMID- 7575936
TI  - Measuring the use of the population perspective on internal medicine attending
      rounds.
AB  - BACKGROUND: The population perspective (risk-factor assessment, prevention,
      epidemiology, and the social aspects of illness) is increasingly important in
      medical school and residency curricula. The authors designed an observational
      study to assess the population-perspective content of internal medicine teaching
      rounds led by attending physicians at the Columbia-Presbyterian Medical Center.
      METHOD: During eight months in 1992 a trained research assistant used a
      structured observation form in observing attending rounds. Population scores were
      calculated by totaling the number of times population-perspective topics were
      mentioned during each case presentation (one point was awarded per mention, with
      an additional point being added for discussions lasting 30 seconds or more). Chi
      square tests and unpaired t-tests were used to compare scores between teams with
      one generalist and one subspecialist attending physician and teams with two
      subspecialists. RESULTS: Fifteen teams and 368 patient presentations were
      observed. The mean population scores were 24.5 for teams with generalist
      attending physicians and 17.9 for teams with subspecialists only (p < .0001). The
      population scores for individual case presentations ranged from 2 to 55.
      CONCLUSION: The population-perspective topics were raised more frequently on the
      internal medicine teaching rounds when a generalist attending physician was
      present than when there were only subspecialist attending physicians.

PMID- 7575935
TI  - A surgery oral examination: interrater agreement and the influence of rater
      characteristics.
AB  - BACKGROUND: Poor interrater reliability is a common objection to the use of oral
      examinations. METHOD: In 1990 the authors measured the agreement of 140 U.S. and
      Canadian surgical raters and the influences, if any, of age, years in practice,
      and experience as an examiner on individual oral examination scores. Eight actor
      examinees memorized transcripts of actual oral examinations and were videotaped
      using a single examiner. Examinee verbal style, dress, content of answers, and
      gender were purposefully adjusted. A repeated-measures analysis of variance was
      used for data analysis. RESULTS: Three aspects of examinee performance influenced
      scores (verbal style, dress, and content of answers). No rater characteristic
      significantly affected scores. Raters showed high agreement (86%) when rating
      "good" performances but less agreement (67%) when rating "poor" performances.
      CONCLUSION: The oral examination scores were not influenced by rater selection.
      The raters ranked good performances more consistently than poor performances.
      Therefore, more than one examiner appears necessary to confirm a poor performance
      during an examination.

PMID- 7575937
TI  - Using faculty and student perceptions of group dynamics to develop
      recommendations for PBL training.
AB  - BACKGROUND: In training faculty as tutors for problem-based learning (PBL),
      certain aspects (domains) of teaching methodology are highlighted in the medical
      education literature. These are content, cognitive processing, and group
      dynamics. The authors contend that the amounts of attention given to these
      domains in faculty and student development have not been equal and that group
      dynamics needs further attention. METHOD: In March 1993 the authors conducted a
      time-lapse study that involved 27 first-year students and three faculty in three
      PBL groups at the University of Toronto Faculty of Medicine. The purpose of the
      study was to determine faculty and student perceptions and knowledge of effective
      group dynamics, and to develop recommendations for student and faculty training.
      A qualitative approach was used that combined projective questions, post-tutorial
      questionnaires, and live and videotaped observations. RESULTS: Observations and
      analysis of the data revealed a generally low awareness of effective group
      dynamics and the absence of a mechanism for reflection that could help groups
      analyze and learn from their behaviors. The results also revealed a discrepancy
      between self-reported behavior and observed behavior. For example, the students
      and faculty perceived their groups as generally "working well as a team," but
      observers noted that several aspects of group productivity (such as the
      articulation of goals and planning for future sessions) were not addressed.
      CONCLUSION: The authors recommend that medical schools develop comprehensive
      training programs to teach group members to evaluate group performance and engage
      in open discussion of effective and ineffective behaviors.

PMID- 7575938
TI  - Maternity and parental leave policies at COTH hospitals: an update. Council of
      Teaching Hospitals.
AB  - Because residents' demands for parental leave are increasing, updated information
      about maternity and paternity leave policies was solicited from hospitals that
      are members of the Council of Teaching Hospitals (COTH) of the AAMC. A 20-item
      questionnaire, combining forced-choice categories and open-ended questions, was
      faxed to 405 COTH hospitals in October 1994; 45% responded. A total of 77% of the
      respondents reported having written policies for maternity and/or parental leave;
      in 1989, only 52% of COTH hospitals had reported having such policies. Forty-one
      percent of the 1994 responding hospitals offered dedicated paid maternity leave,
      with a mean of 42 days allowed. Twenty-five percent of the respondents offered
      paternity leave, and 15% offered adoption leave. It is encouraging that the
      majority of the teaching hospitals that responded to the survey had adopted
      written policies, but the 23% without written policies remain a source of
      concern. Well-defined policies for maternity, paternity, and adoption leave can
      reduce stress and foster equity both for trainees requiring leave and for their
      colleagues.

PMID- 7575939
TI  - Rethinking faculty development.

PMID- 7575941
TI  - Confronting the costs of ambulatory-care training.

PMID- 7575940
TI  - Rethinking faculty development.

PMID- 7575944
TI  - Personal values and primary care specialty aspirations.

PMID- 7575942
TI  - Osteopathic GME consortia.

PMID- 7575943
TI  - Concerns about psychological testing for family practice residents.

PMID- 7575946
TI  - Physician-patient partnership in managing chronic illness.

PMID- 7575947
TI  - The debate over electives--1899.

PMID- 7575945
TI  - Helping medical students develop lifelong strategies to cope with stress.

PMID- 7575948
TI  - Introduction: why another conference on family violence?

PMID- 7575949
TI  - From battered children to family violence: what lessons should we learn?
AB  - Child abuse is an ancient problem but one that has grown alarmingly in the United
      States in the last few decades. Once the problem of child abuse was recognized in
      the 1960s, mandatory reporting was instituted to develop public health mechanisms
      for intervention. But the approaches taken then were inadequate, and as sexual
      abuse of children was acknowledged, social service agencies gradually devolved
      from providing help to simply investigating, a trend that has contributed to the
      present emergency situation. Proper knowledge of how best to treat and prevent
      child abuse is scarce; this makes it harder to base an educational program in
      family violence on sound evidence. Also, public awareness of child abuse is far
      ahead of efforts to intervene and prevent it. Neither federal nor state laws have
      clear policies about what child protection strategies should be, which inhibits
      professionals who are attempting to deal with the problem. National guidelines
      and resources are needed, although efforts to solve the problem are best
      approached on a local level. Any teaching program on child abuse should discuss
      the policy alternatives, and any group that is helping children and their
      families must agree on a policy to guide its work. The author maintains that the
      child protection system should be run not by county or state governments but by
      the private and public health care system because this system has greater
      financial resources, has a tradition of scientific inquiry, and is still
      perceived as a "helping" system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575950
TI  - Education and research in adult family violence: a perspective.
AB  - There are compelling reasons to promote the education of medical students about
      family violence. First, such violence is a significant health problem, but one
      that has been hidden or ignored for too long by the medical and health
      communities and even by law enforcement agencies. Once physicians look for family
      violence among their patients, however, they will find it. Second, it is
      important for physicians to know about family violence because they typically are
      the first line of defense and will see victims of family violence who cannot, or
      are afraid to, call the police. A third reason for including family violence in
      the curriculum is that this topic is eminently teachable. Obstacles to greater
      emphasis on family violence in the curriculum are akin to the obstacles in
      physicians' practices: ignorance, denial, a feeling that the problem is a law
      enforcement one, and a mistaken notion about how easy it is for an abused woman
      to leave her abuser. Also, medical students often come from sheltered backgrounds
      and will have to be taught about the prevalence and importance of family
      violence. Curricula in family violence should be multidisiplinary, integrated
      into current teaching, and have an emphasis on experiential learning. Also,
      change must be built into the curriculum so that it can reflect the latest
      understanding of the problem. Faculty who have the interest and training to teach
      this topic are limited, so they must teach their colleagues to prevent
      misinformed teaching. Finally, community resource people should be involved,
      since they are responsible for much of the management and rehabilitation of
      abused persons.

PMID- 7575951
TI  - Cultivating curricular reform.
AB  - Since the 1960s there has been pressure to reform medical education in a more
      humanistic direction. One reason this has been difficult is that most medical
      schools have been forced to maintain themselves on resources allocated to support
      research and the technology of specialized tertiary care. Nevertheless, many
      people believe that medical education can still change because of changes taking
      place outside the sciences, such as a redefinition of the meaning of health and
      the need to provide better health care to the U.S. population at a lower cost.
      Taking this optimistic view will help strengthen reformers' resolve for
      curricular change and the incorporation of important areas such as family
      violence into medical students' education. There are numerous barriers to
      curricular change. Yet there are useful principles that can guide reform efforts,
      such as having an explicit rationale for the desired change, focusing on
      educational goals rather than on resources for their implementation, recruiting
      support from the departmental and school leadership, anticipating negative
      reactions, and recognizing the need for negotiation. There are also principles to
      foster successful implementation, the most important of which is to have everyone
      involved agree on the goals of the new program and participate in the process.
      The way to increase an emphasis on family violence issues is to find areas in the
      curriculum where these issues can be integrated with current teaching. Finally, a
      medical school curriculum on family violence does not need to be all-inclusive,
      but instead should prepare a good foundation so that students can expand their
      knowledge and skills during residency training and medical practice.

PMID- 7575952
TI  - Making a place for teaching about family violence in medical school.
AB  - Although family violence is a common cause of patients' problems, it has not yet
      received sufficient attention in medical school curricula. There are several
      possible reasons for this delay, including the fact that teaching about family
      violence is complicated because there are no "quick fix" interventions, the
      approaches are often complex and multidisciplinary, and there may be limited
      resources for response in many communities. The author offers a variety of
      suggestions for incorporating family violence topics in the medical school
      curriculum, such as: (1) expose students to information about family violence in
      their preclinical training, and integrate family violence issues into clinical
      instruction (several examples are given); (2) use problem-based teaching formats
      when possible, since these lend themselves well to the integration of family
      violence issues into case presentations; (3) enrich the curriculum by the
      participation of a variety of non-MD experts who deal with family violence
      issues, and take students out of the classroom to shelters and other relevant
      locations; (4) teach a prevention-oriented approach, just as is taught for the
      areas of smoking, seat belt use, weight control, etc.; (5) use standardized
      patients, interactive computer-based learning, and other innovative methodologies
      to help preclinical students perfect their interviewing and examination skills;
      (6) during the clinical years, include violence as part of the differential
      diagnosis of common medical complaints; (7) give attention to the education of
      residents for consistent teaching and reinforcement of principles learned in
      medical school, and integrate family violence education into the entire continuum
      of physicians' education; (8) build appropriate expectations into accreditation
      requirements and into medical licensing and specialty certifying
      examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7575953
TI  - Elder abuse: definitions and implications for medical education.
AB  - Elder abuse is a growing problem as the number of dependent older persons
      increases and the proportions of middle-aged and younger children--who themselves
      are struggling with problems of their own families and finances--decline. As this
      occurs, older women increasingly will dominate the ranks of the elderly. These
      realities make it imperative for medical students to become familiar with the
      care of older persons, including abused older persons, who, at present,
      constitute at least 2% of the population over 65. The author outlines the causes
      of elder abuse (e.g., previous abusive relationships in a family increase the
      likelihood of elder abuse); lists important barriers to diagnosis and management
      of the abused (e.g., the physician's uncomfortable position between protecting
      confidentiality, serving as an advocate for the patient, and needing to
      collaborate with the family--and often the abuser); and outlines the various
      forms of intervention that are available (e.g., assistance of adult protection
      services). Education in elder abuse should be distributed across the entire
      medical student curriculum (many examples are given) and should be dominated by
      case-based learning at a variety of sites, such as hospitals, clinics, and
      subacute care units. The author closes by reiterating the urgent need to prepare
      physicians now to deal with a problem of increasing magnitude, severity, and
      ugliness.

PMID- 7575954
TI  - Strategic footholds for medical education about domestic violence.
AB  - The author describes in detail the successful education initiatives on domestic
      violence, especially violence against adult women, that have been implemented for
      family medicine residents at the St. Paul-Ramsey Medical Center in St. Paul,
      Minnesota, and for medical students at each of the three Minnesota medical
      schools. For example, in 1990 the residency program adopted a community-oriented
      primary care approach to teaching and clinical activities, including the area of
      domestic violence. This approach stresses partnerships with community
      organizations that deal with domestic abuse. Also developed was a curriculum to
      help residents deal with their apprehension about domestic violence and acquire
      the knowledge, attitudes, and skills they need to confront this problem
      effectively. At the three medical schools, teaching about domestic violence takes
      place in preclinical courses, during clinical rotations (where students work with
      abuse victims), and through extracurricular activities. The author describes some
      important types of resistance to having instruction about domestic violence in
      the medical curriculum. To move forward, faculty must overcome their discomfort
      with the topic yet acknowledge that teaching about it is difficult and requires
      personal stamina and empathy with colleagues. Faculty must also agree to
      collaborate with those who have sensitivity and expertise in the area, and must
      make a long-term commitment to prepare physicians to recognize problems of
      domestic violence and work effectively with its victims and perpetrators.

PMID- 7575955
TI  - Prevention of family violence.
AB  - Physicians must learn to recognize the victims of family violence among their
      patients and must then work to prevent such abuse. To help provide information
      that can help physicians understand and prevent family violence, the Centers for
      Disease Control and Prevention (CDC) is involved in gathering data that will
      enable scientists (1) to see the patterns of family violence, (2) to determine
      the risk factors, and (3) to evaluate interventions to prevent future violence.
      Then the task will be (4) to establish programs of prevention on a successful
      scale. The author describes several specific CDC programs designed to meet these
      four goals, with the ultimate goal being the drastic lowering of incidences of
      family violence. Medical schools can help reach that goal by using the knowledge
      gained by such research for curriculum development to train physicians to treat
      and prevent family violence.

PMID- 7575956
TI  - [Level of immunoglobulins A, G and M in the postoperative period].
AB  - There are very different points of view in the literature concerning the
      application of immunoglobulin preparations in the prophylaxis of septic
      complications or in the therapy of the sepsis syndrome. Indication for
      immunoglobulin substitution therapy with commercial products requires a critical
      new approach. Daily measurement of the immunoglobulin A, G and M serum levels may
      help in cases of deficiency. The high expectations placed in immunoglobulin
      therapy in cases of septic syndrome have not been fulfilled because of its
      complexity. Our own examinations were done to look for defects in the
      immunological system in the postoperative period and to make targeted
      substitutions. We compared the immunoglobulin levels in patients with and without
      postoperative septic complications. If there was a deficiency, we added 30-35 g
      Venimmun, but the immunological situation was not better than before, with regard
      to the serum levels. According to the literature, prophylaxis with immunoglobulin
      preparations is not useful to reduce the therapeutic period in an intensive care
      unit. The further development of septic complications, especially with regard to
      mortality, could not be influenced.

PMID- 7575957
TI  - [Plasma catecholamine level and clinical parameters--quality criteria for
      premedication in childhood].
AB  - Stress hormones noradrenaline and adrenaline were measured in plasma before and
      after premedication to objectivate the anxiolytic potency of different
      premedication methods in children. In addition indirect signs of
      sympathoadrenergic activity (heart rate and blood pressure) as well as children's
      behavior and reaction to face mask were documented. Each group consisted of 16
      children (aged 3 to 15 years). One group was prepared only psychologically, the
      second group received 0.1 mg/kg midazolam intravenously and the third group was
      given 1 mg/kg promethazine orally. Blood pressure and heart rate decreased after
      premedication, mainly in the midazolam group. After mask exposition in all groups
      noradrenaline and adrenaline levels increased with the exception of adrenaline in
      the midazolam-group, where the levels remained low. Mask acceptance and
      anxiolysis were better in the midazolam-group than in other groups. Reduction in
      heart rate and blood pressure, catecholamines in plasma, anxiolysis and a high
      mask acceptance indicate that intravenous administration of midazolam is very
      effective in premedicating children.

PMID- 7575958
TI  - [Effect of duration of infusion on elimination rate of alfentanil].
AB  - In the present study the disposition of alfentanil after cessation of a constant
      rate infusion was compared with intravenous bolus injections. In 11 patients
      undergoing intervertebral disk surgery general anaesthesia was induced with
      midazolam, alfentanil and vecuronium; anaesthesia was maintained with a constant
      rate infusion (1.5 to 2 micrograms/kg/min, 1.0 micrograms/kg/min at the end of
      the infusion period) of alfentanil. The parameters of bolus injections were
      obtained from 5 patients undergoing lithotripter therapy; an intravenous bolus of
      15 micrograms/kg was given. After infusion times of 60 to 120 minutes the mean
      elimination half life of alfentanil was significantly increased (227 +/- 166 min)
      compared to the bolus injection (50.8 +/- 9.5 min). There were significant
      correlations of the elimination half life with the age (r = 0.53, p = 0.03) of
      the patients, the total dose (r = 0.607, p = 0.01) and the infusion time (r =
      0.612, p = 0.01). The total clearance of alfentanil in the bolus group was 385 +/
      138 ml/min and in the infusion group 620 +/- 215 ml/min. There were no
      significant correlations between the total clearance of alfentanil and the total
      dose and between the duration of infusion and total clearance. The clinical
      implications of our study: After prolonged continuous infusions of alfentanil a
      significant reduction of the elimination rate has to be considered. The patients
      must be observed very carefully in the recovery room in order to prevent a
      possible respiratory depression.

PMID- 7575959
TI  - Average vs normal.

PMID- 7575960
TI  - Stress fatigue: basic principles and prosthodontic implications.
AB  - Clinical evidence indicates that the majority of fractures that occur in
      prosthodontic structures do so after a period of many years. Such failures
      generally are not related to an episode of acute overload but result from fatigue
      failure. This paper reviews the current knowledge of fatigue failure and test
      methods. An overview of published studies is given, and the authors suggest
      guidelines for future prosthodontic studies of this nature.

PMID- 7575961
TI  - Adaptation of finger-smoothed irreversible hydrocolloid to impression surfaces.
AB  - This study investigated a surface moistening technique in which the surface of an
      irreversible hydrocolloid impression material was smoothed using a moistened,
      gloved finger prior to impression making. To determine the effect of the
      procedure on the surface integrity of machined brass die, impressions with and
      without smoothed surfaces were made and examined. Similarly, multiple impressions
      were made for a single dentate subject, and stone casts were poured. These casts
      were assessed by three experienced clinicians. Results indicated that the
      moistened finger technique resulted in fewer surface bubbles and voids than did
      impressions made when the material was only loaded with a spatula and not
      smoothed.

PMID- 7575964
TI  - Patient-assessed security changes when replacing mandibular complete dentures.
AB  - Twenty edentulous patients had unsatisfactory dentures replaced in a student
      clinic, using conventional techniques, under consultant supervision. Three visual
      analogue scale records of self-assessed mandibular denture security were made
      while the dentures were fabricated, and two were made following placement of the
      new dentures to measure any changes occurring. The method appeared reliable, and
      significant improvements in security were recorded. The percent increase in
      security and the coefficient of variation of the preplacement visual analogue
      scale scores were each inversely proportional to the preplacement visual analogue
      scale scores. This relationship may be useful in the identification of patients
      with special problems.

PMID- 7575962
TI  - The effect of pH on the cytotoxicity of eluates from denture base resins.
AB  - This in vitro study examined the effects of environmental pH on elution of
      potentially toxic substances from heat-, light-, and dual- (chemical plus light)
      polymerized denture base resins. Eluates were prepared by daily transfer of disks
      to fresh buffers at pH 4.0, 5.0, and 6.8 over a 5-day period. Oral epithelial
      cells were plated in culture dishes in medium containing the eluate. After 24
      hours, cellular RNA synthesis was assessed by measuring tritiated uridine uptake.
      Effects of materials were compared to identical cultures that contained the
      appropriate buffer without the eluate. The results indicate that the cytotoxic
      components leach out of the denture base resins in different amounts and at
      different rates, and the amount of leaching can be affected by pH.

PMID- 7575963
TI  - Adhesion of restorations to impression materials.
AB  - Three impression materials, Impregum, Permadyne, and Reprosil, were tested with
      three restorative materials, Lodestar, Dispersalloy, and Concise. Polished
      cylindrical samples of each restorative material with and without a collar design
      were used for impression retention testing. A pullout test using an Instron
      machine was used to test the samples that were individually submerged in the
      impression materials until set. Results show similar behavior for Lodestar and
      Dispersalloy with and without a collar. Permadyne and Impregum were significantly
      more retentive with resin composite than was Reprosil. Resin composite was
      significantly more retentive than the metals. Impression materials may bond with
      restorative materials, significantly increasing resistance to impression removal.

PMID- 7575966
TI  - The effect of glutaraldehyde and microwave disinfection on some properties of
      acrylic denture resin.
AB  - This study evaluated the effect of disinfection methods on the dimensional
      stability, flexural properties, and microhardness of a heat-polymerized denture
      acrylic resin. A 1- and 12-hour immersion period in 2% alkaline glutaraldehyde,
      and 3- and 15-minutes exposure to microwaves were employed as disinfection or
      sterilization procedures. Storage in water for 1 and 12 hours were used as the
      control. For each procedure 10 specimens were used. The results indicated that
      the linear changes observed were of no clinical importance. The same conclusion
      can be drawn for flexural properties and microhardness. The microwave method is a
      useful alternative to immersion disinfection.

PMID- 7575965
TI  - In vitro and in vivo evaluation of a new Opaque system for metal ceramic
      restorations.
AB  - This study made an in vitro comparison of the shear strength in a corrosive
      solution, the scanning electron microscopy of the processing steps, and the x-ray
      powder diffraction analyses of a newly developed opaque system (Biopaque) with a
      traditional opaque-system (Opaque P). Clinically, two traditional opaque systems
      (Opaque P and Vita-VMK-Paint-On 88 opaque) were compared to Biopaque over a 4
      year period. A total of 218 metal ceramic units were placed for 29 patients. One
      hundred ten were veneered with Biopaque, 50 with Opaque P, and 58 with Vita-VMK
      Paint-On 88. The technical failure rate of the metal ceramic restorations was
      9.6%, and the biological failure rate 5.5%. There was no significant difference
      of the shear strength in a corrosive solution between Biopaque and the
      traditional opaque system (Opaque). The x-ray powder diffraction analyses
      revealed that only the base paste of Biopaque was a newly developed material. In
      this study, the new opaque system (Biopaque) showed the same in vitro and in vivo
      results as the other conventional opaque systems. However, at least 5 years of
      clinical evaluation are necessary before this new opaque system can be completely
      recommended.

PMID- 7575967
TI  - Load fatigue of teeth restored with cast posts and cores and complete crowns.
AB  - Twenty-five extracted human central incisors were divided into five groups and
      prepared for complete cast crowns. Test teeth had cast dowel cores fabricated
      with the ferrule height varying from 0.5 to 2.0 mm in 0.5-mm increments. The five
      control teeth did not have cast dowel cores. A 4.0-kg load was applied to each of
      the restored teeth at an angle of 135 degrees to the long axis of each tooth.
      This load was applied cyclically at a rate of 72 cycles per minute. The load
      application point was predetermined by a waxing jig that was used to wax all
      crowns. The primary variable was the ferrule length. The independent variable was
      the number of load cycles required to create preliminary failure. Preliminary
      failure was defined here as the loss of the sealing cement layer between crown
      and tooth. An electrical resistance strain gauge was used to provide evidence of
      preliminary failure. The results of this study showed that the 0.5 mm and 1.0 mm
      ferrule lengths failed at a significantly lower number of cycles than the 1.5 mm
      and 2.0 mm ferrule lengths and control teeth.

PMID- 7575968
TI  - Evaluation of machining accuracy and consistency of selected implants, standard
      abutments, and laboratory analogs.
AB  - Thirteen implants having external hexagonal extensions were evaluated for
      machining accuracy and consistency. A composite score was derived to evaluate
      overall manufacturing accuracy and consistency of the implants evaluated in this
      study. A technique to determine the rotational freedom between implant and
      abutment is described, and the coronal hexagonal matings of selected implants and
      abutments is evaluated and reported. Crossover use and combinations of products
      from different manufacturers was also evaluated for rotational freedom. Two
      nonexternal hexagonal extension implant configurations were measured for
      rotational movement as contrasting and comparative values.

PMID- 7575970
TI  - Characterization of treated porcelain surfaces via dynamic contact angle
      analysis.
AB  - Successful porcelain repair requires conditioning of porcelain surfaces.
      Conditioning is intended to facilitate wetting by repair materials and improve
      interfacial bonding. The objective of this investigation was to determine the
      effects of selected surface treatments upon the wettability of a representative
      feldspathic porcelain. Dynamic contact angle analysis and scanning electron
      microscopy were used to characterize the effects of such treatments. Standardized
      porcelain specimens were subjected to the following five treatment regimens: (1)
      control (no treatment); (2) airborne particle abrasion using 50 microns aluminum
      oxide; (3) etching with ammonium bifluoride gel; (4) etching with acidulated
      phosphate fluoride gel; and (5) etching with hydrofluoric acid gel. Following
      treatment, specimens were cleansed and dried. Advancing contact angles were
      quantified using dynamic contact angle analysis. Mean values and 95% confidence
      intervals were (in degrees): control, 63.8 +/- 2.7; ammonium bifluoride, 39.4 +/-
      2.0; airborne particle abrading, 29.1 +/- 2.9; acidulated phosphate fluoride,
      24.9 +/- 1.7; and hydrofluoric acid, 16.5 +/- 1.2. Significant differences were
      found between all treatment groups (P = .05). Subsequent scanning electron
      microscopy examination of treated surfaces indicated lesser contact angles were
      associated with surfaces displaying deeper and wider grooves. Apparently, the
      resultant increase in surface area produces increased wettability. It is inferred
      that an increase in surface area may correspond to enhanced resin-porcelain
      bonding.

PMID- 7575971
TI  - Marginal accuracy and fracture strength of conventional and copy-milled all
      ceramic crowns.
AB  - In this comparative in vitro study, the marginal accuracy and fracture strength
      of conventional and copy-milled In-Ceram crowns were examined. Anterior crowns
      with medians of 32.5 microns for the conventional technique and 38 microns for
      the copy-milled units had significantly smaller gaps than premolar crowns that
      had a median marginal gap of 45 microns for both techniques. There was a
      significant difference in fracture strength only for anterior crowns. The study
      indicates that copy-milled In-Ceram crown have clinically acceptable margins and
      fracture strength and reduce laboratory fabrication time.

PMID- 7575969
TI  - Influence of surface treatment on bond strength between a heat-activated and a
      light-activated resin composite.
AB  - The shear bond strength of two light-activated resin composite materials to a
      preformed heat-polymerized resin material was measured. The substrate was a
      urethane dimethacrylate material designed for use as a direct bonded pontic. In
      the first phase of the study, the shear bond strength between the substrate and a
      urethane-based resin composite and seven surface treatments was evaluated. In the
      second phase, a Bis-GMA resin composite and three surface treatments were
      studied. The study showed that a bonding agent was essential for the achievement
      of an adequate bond strength between the light-activated and heat-polymerized
      resin. However, there was a significant difference in bond strength depending on
      the type of light-activated resin composite and bond agent used. A Bis-GMA-based
      light-activated composite, together with its bond system (22.82 MPa), provided
      higher bond strength than a urethane-based resin composite and its bonding system
      (14.45 MPa). There was a direct relationship between cohesive failure and bond
      strength; as bond strength increased, the number of cohesive failures increased
      as well.

PMID- 7575973
TI  - A clinical evaluation of In-Ceram crowns.
AB  - In this investigation, 63 In-Ceram crowns were placed in 45 patients in both
      dental school and private practice settings. The restorations were observed for a
      period of 24 to 44 months, with a mean of 37.6 months. Both anterior and
      posterior teeth were treated and occlusal conditions were recorded. One crown
      fractured, yielding a 98.4% success rate. The single fracture was attributed to
      crown preparation geometry.

PMID- 7575972
TI  - Effect of surface finish on the flexural strength of feldspathic and aluminous
      dental ceramics.
AB  - The effects of surface finish on flexural strength of a feldspathic porcelain,
      aluminous porcelain, and a computer aided design-computer aided machining
      porcelain (Vitabloc MKI) were examined. A total of 105 bars of the feldspathic
      ceramic were made, randomly divided into seven groups, and sintered according to
      manufacturer's recommendations. The groups consisted of as-fired, self-glazed,
      overglazed, ground, polished, ground/annealed, and polished/annealed. A total of
      45 bars of the aluminous ceramic and Vitabloc MKI were made and randomly divided
      into three groups: as-fired, ground, and polished. Overglazing, grinding, and
      polishing all significantly increased (P < .05) the flexural strength (four-point
      bend test) of the tested materials (15% to 30%).

PMID- 7575974
TI  - Tensile bond strength of gold and porcelain inlays to extracted teeth using three
      cements.
AB  - This in vitro study compared the tensile bond strength of gold and porcelain
      inlays to extracted molars in standardized cavities. Three cements were used:
      zinc phosphate, glass-ionomer, and a resin composite cement. The gold inlays were
      cemented using zinc phosphate or glass-ionomer cement, and the porcelain inlays
      were luted using resin composite or glass-ionomer cement. Surface treatments
      included, for gold inlays, either no treatment (zinc phosphate cement) or
      airborne particle abraded and tinplated (glass-ionomer cement); and for porcelain
      inlays, either no treatment (glass-ionomer cement) or etched and silane-treated
      (resin composite cement). Statistical analysis was performed using the Weibull
      distribution. Results showed no significant differences between gold inlays
      cemented using zinc phosphate or glass-ionomer cements and porcelain inlays luted
      using glass-ionomer cements. The bonded porcelain inlays (resin composite cement)
      showed tensile bond strengths two to three times higher than those obtained for
      cemented gold inlays.

PMID- 7575975
TI  - Fabrication of titanium implant-retained restorations with nontraditional
      machining techniques.
AB  - Traditional laboratory techniques are being supplemented by modern precision
      technologies to solve complex restorative problems. Electrical discharge
      machining combined with laser scanning and computer aided design-computer aided
      manufacturing can create very precise restorations without the lost wax method. A
      laser scanner is used to create a three-dimensional polyline data model that can
      then be converted into a stereolithography file format for output to a
      stereolithography apparatus or other rapid prototyping device. A
      stereolithography-generated model is used to create an electric discharge
      machining electrode via copper electroforming. This electrode is used to machine
      dental restorations from an ingot of titanium, bypassing the conventional lost
      wax casting process. Retaining screw access holes are machined using conventional
      drilling procedures, but could be accomplished with electric discharge machining
      if desired. Other rapid prototyping technologies are briefly discussed.

PMID- 7575976
TI  - Variable reduced metal support for collarless metal ceramic crowns: a new model
      for strength evaluation.
AB  - A newly designed specimen allowed strength testing of simulated collarless metal
      ceramic crowns. The design provided precision replication of specimens having
      ceramic veneers that were completely supported by metal or that were extended 1
      and 2 mm beyond the metal support. Twelve specimens of each design were loaded to
      failure at angles of 90, 45, and 6 degrees. Specimens with unsupported extensions
      approximated the compressive strength of those with complete framework support
      (means of 291.6 MPa, 320.2 MPa, and 335.9 MPa, respectively, for 1 mm, 2 mm, and
      0 mm of porcelain extension) when tested at 90 degrees. However, for
      corresponding porcelain lengths, mean resistance to fracture at an angle of 45
      degrees was 7.3, 11, and 5.8 times smaller, and at an angle of 6 degrees, 45, 60,
      and 25 times smaller. The differences were highly significant (P < .001). These
      results suggest that collarless metal ceramic crowns having up to 2 mm of
      unsupported porcelain could resist the same axial pressure as those restorations
      with complete metal support, provided a 90-degree shoulder tooth preparation is
      used.

PMID- 7575977
TI  - Mechanical property and microstructural variations for recast low-gold alloy.
AB  - Using polystyrene plastic patterns meeting the dimensional requirements of
      ANSI/ADA specification no. 5, tension test specimens were recast multiple times
      from a popular Type III gold (46%) alloy. The alloy was melted by electrical
      heating in a graphite crucible and four conditions were compared: new alloy and
      alloy cast two, three, and four times (n = 4). After casting, age-hardened
      specimens were loaded at an elongation rate of 0.5 mm/min until failure, and the
      stress-strain plots were recorded. Values of yield strength, tensile strength,
      and percentage elongation for the specimen groups were analyzed by one-way
      analysis of variance, followed by the Student-Newman-Keuls multiple range test.
      Significant decreases (P < .01) in yield strength and percentage elongation
      occurred with recasting, although there were no significant differences (P > .05)
      in tensile strength. Scanning electron microscope examination revealed that the
      number of casting defects increased with remelting, and that their presence
      dominates the tensile fracture process. The variation in mechanical properties of
      the alloy with remelting was attributed to these casting defects.

PMID- 7575978
TI  - Metal allergy in dentistry: detection of allergen metals with X-ray fluorescence
      spectroscope and its application toward allergen elimination.
AB  - Numerous metal allergies possibly resulting from intraoral metal restorations
      have been reported, although the mechanism of onset is not yet completely
      understood. Allergen elimination may be the most effective treatment, and
      location of allergen metal becomes essential. The x-ray fluorescence spectroscope
      was used to detect the allergen metals in intraoral metal restorations and
      personal and household items of metal allergy patients. The apparatus was
      evaluated preceding its clinical application, and restorations and personal items
      for 381 patients were analyzed to detect allergens. Successful diagnoses and
      allergen elimination treatment of three patients are reported.

PMID- 7575979
TI  - Three-dimensional movements of a maxillary complete denture: the development of a
      measuring system and preliminary measurement.
AB  - To measure the movements of a maxillary denture in vivo it is necessary to
      analyze the three-dimensional displacements induced. A measuring system
      consisting of four main units (a magnetic sensor, three optical fiber sensors, a
      sensor-setting jig, and a recorder) was developed. Using this system, the
      movements of a maxillary denture were continuously measured during tapping and
      during the mastication of a peanut.

PMID- 7575981
TI  - An investigation of preferable taper and thickness ratios for cast
      circumferential clasp arms using finite element analysis.
AB  - This study used a two-dimensional finite element method to investigate the
      preferred design for a cast circumferential clasp. Finite element models of the
      clasp arm with the constant flexibility were constructed, the stress was
      calculated, and the effects of taper and cross-sectional shape on stress were
      evaluated. The clasp arm with the taper of 0.8 showed less stress than those with
      other tapers, and the thinner and wider arms showed less stress than those with
      other cross-sectional dimensions. These results suggest that the use of the
      preformed clasp-pattern with a taper of 0.8 is preferable for reducing fatigue
      and/or permanent deformation of the clasp arm.

PMID- 7575980
TI  - A magnetic resonance imaging study of centric maxillomandibular relation.
AB  - The authors conducted research to determine the structural relationships of the
      craniomandibular articulation that resulted when a mandibular reference position
      was established. A noninvasive clinical method was used to identify and record
      centric maxillomandibular relation in normal subjects and a suitable reference
      position in subjects with derangements of the craniomandibular articulation. The
      reference positions were checked for repeatability. Magnetic resonance imaging
      was used to determine the intraarticular relationships resulting from application
      of the clinical techniques. The normal subjects conformed well to the 1987
      "Glossary of Prosthodontic Terms" definition, with the mandible close to first
      tooth contact. In subjects with deranged articulations, the condyle was always in
      an abnormal relationship on the affected side in the reference position, and
      there were many intersubject variations.

PMID- 7575982
TI  - Practical nursing measures for vascular compromise in the lower leg.
AB  - Among the many factors that contribute to a nonhealing wound, circulatory
      compromise is a dominant variable. Regardless of whether the circulatory
      compromise is arterial or venous, the patient should be educated and supported in
      their efforts to quit smoking, minimize stress, achieve ideal body weight, limit
      fats in their diet, keep underlying disorders within check, and avoid a sedentary
      lifestyle. Patients with peripheral arterial disease (PAD) can maximize their
      tissue perfusion when nurses help them implement a few basic strategies into
      their lifestyles. Patients with chronic venous insufficiency (CVI) need to apply
      counterpressure and combat gravity to reduce venous hypertension, without which
      healing will not occur. When resources are limited, nurses can bridge the gap
      through coordination of care, patient teaching and support.

PMID- 7575983
TI  - A model for change in delivering community leg ulcer care.
AB  - Leg ulcer care has largely been provided by community nursing staff in the UK.
      However, the treatment of leg ulcers has been accompanied by high cost and poor
      healing rates. As part of an initiative in a single district of the UK, six
      community leg ulcer clinics were established and a system of audits implemented
      to monitor their progress over two years. Improvements were demonstrated in the
      success of the patient referral system, correct assessment of patients with
      significant arterial leg disease, effective use of dressings, follow-up to
      prevent ulcer recurrence, improved nursing education in leg ulcer care, vastly
      improved healing rates during the first twelve weeks of treatment compared to
      patients in a pre-study audit, reduced pain and increase in the ability of
      patients to perform activities inside and outside the home, and a cost reduction
      from an estimated $680,000 per annum to $250,000 in the study district. The model
      of care implemented in these community clinics can be adapted to other
      communities. Priority must be given to auditing outcomes and changes to ensure
      that the most effective care is delivered in each community.

PMID- 7575984
TI  - A brief review of the pathophysiology and treatment of cutaneous T-cell lymphoma
      "mycosis fungoides".
AB  - Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. It
      represents a spectrum of disorders with preferential involvement of the skin and,
      after a period of time, may progress to involve lymph nodes, peripheral blood
      and/or visceral organs. MF progresses in three clinical phases: the premycotic,
      mycotic and tumor stages. Each stage has different characteristics and goals for
      treatment. Treatment such as chemotherapy and radiotherapy in the earlier stages
      is more effective and may be curative, while treatment in the last stage is less
      effective and the intent is to alleviate symptoms. The case study illustrates
      topical treatment using sheet hydrogel to absorb exudate, contain odor and reduce
      pain upon dressing removal for a patient in the tumor stage of MF.

PMID- 7575985
TI  - Skin temperature and moisture management with a low air loss surface.
AB  - Important factors in the prevention and treatment of pressure ulcers are the
      maintenance of the physiological conditions of skin temperature and skin moisture
      level. Low air loss (LAL) therapy is a method of maintaining these conditions.
      The changes in the skin temperature and skin moisture level with an LAL support
      system were compared to those with a standard hospital mattress (SHM). The study
      was conducted on ten volunteers in the supine position for three hours in warm
      ambient room conditions. Skin temperature was measured continuously. The moisture
      level of the skin was determined using direct and indirect indicators. The
      results showed that, on the average, the skin temperature on the LAL system was
      1.2 degrees F lower than that on the SHM (p = 0.0001). With the Moisture Vapor
      Transmission Rate skin moisture indicator, the moisture gain above normal with
      the LAL system was 87 percent lower than that with the SHM (p = 0.01). Similarly,
      with the conductance skin moisture indicator the conductance increase above
      normal with the LAL system was 96 percent lower than that with the SHM (p =
      0.01). These results demonstrated the ability of the LAL system to maintain
      normal skin temperature and moisture content and aid in the protection against
      skin damage.

PMID- 7575987
TI  - DNA alkylation by minor groove-binding N1-alkoxyalkyl-bis-benzimidazoles.
AB  - Two groups of isomeric N1-alkoxyalkyl-bis-benzimidazoles differing in the
      orientation of the N-alkoxyalkyl group (R) with respect to the DNA minor groove
      have been examined as to their reaction with DNA. Agarose gel mobility shift
      assay demonstrates that the 'R-inward' isomers alkylate and cause thermally
      induced strand breakage, in contrast to a much weaker reaction of the 'R-outward'
      isomers. Complementary studies using high-resolution polyacrylamide gel
      electrophoresis confirmed relatively weak but definite alkylation-induced thermal
      cleavage at all available G base sites, but at selected A sites. The alkylation
      reaction is interpreted in terms of an SN2 displacement of the alkoxy group by
      nucleophiles within the groove, in contrast to the complete lack of such
      nucleophilic displacement of these drugs in bulk solution. Reaction with all
      available Gs is interpreted in terms of nucleophilic strength within the DNA
      minor groove whereas, in contrast, reaction at the A residues appears to be
      determined primarily by initial molecular recognition of a DNA site by the drug,
      followed by an SN2 displacement. The relative cytotoxic potencies of these drugs
      against KB human tumor cells may be explained on the basis of this mechanism.

PMID- 7575988
TI  - Synthesis, DNA binding, footprinting and in vitro antitumour studies of a meta
      hydroxy analogue of Hoechst 33258.
AB  - An analogue of Hoechst 33258, bearing a phenolic hydroxyl group in the meta
      rather than para position, was designed using molecular graphics to introduce
      hydrogen-bonding potentials between this OH group and the C = O group of cytosine
      9 and the NH2 group of guanine-4', of the opposite strand of the B-DNA duplex,
      d(CGCGAATTCGCG)2. This derivative (meta-Hoechst) was synthesized in seven steps
      and characterized. Its binding to DNA was assessed by measurements of melting
      temperatures (Tm) and found to be similar in strength and AT preference to the
      parent Hoechst 33258 at this gross level. The AT preference of meta-Hoechst and
      Hoechst 33258 was probed further using hydroxyl radical footprinting on the tyrT
      DNA fragment, for which clear footprints were detected at AAT, AAA and ATAT runs,
      as for netropsin and distamycin. Hydroxyl radical footprinting was carried out on
      a trimer of CGCGAATTCGCG cloned into a longer DNA fragment, for which clear
      footprints for both Hoechst 33258 and meta-Hoechst were detected in regions with
      four or more contiguous AT base pairs. Three cell lines derived from
      haematological malignancies were more sensitive to both Hoechst 33258 and meta
      Hoechst than lines derived from solid tumours, but there was no significant
      difference between the activity of these two Hoechst derivatives.

PMID- 7575989
TI  - Effect of synthetic and naturally occurring chalcones on ovarian cancer cell
      growth: structure-activity relationships.
AB  - This study was carried out to determine the effect of 15 different natural and
      synthetic chalcones on the proliferation of both established and primary ovarian
      cancer cells expressing type II oestrogen binding sites (type II EBS). The
      binding affinity of chalcones for type II EBS was also tested. At concentrations
      from 0.1 to 10 microM, chalcones inhibited ovarian cancer cell proliferation and
      [3H]oestradiol ([3H]E2) binding to type II EBS. Considering the structure-related
      variation in IC50 (concentration resulting in a 50% inhibition of cell growth)
      and Di50 (concentration resulting in a 50% displacement of [3H]E2 bound to type
      II EBS), it appeared that the presence of an alpha-beta double bond, the
      hydroxylation in 3 or 2 of ring B and the absence of a prenyl group were
      important to both the antiproliferative and binding activity. Structure-related
      variations in IC50 and Di50 were significantly concordant (Fisher's exact test: P
      = 0.0291), suggesting that there may be a type II EBS-mediated mechanism for
      chalcone antiproliferative activity. Our data indicate that chalcones could be
      considered as potential new anticancer drugs.

PMID- 7575986
TI  - Prodrugs of anthracycline antibiotics suited for tumor-specific activation.
AB  - The two novel prodrugs 4 and 11 have been prepared from tetra-O-acetyl-D
      galactopyranose and doxorubicin in three and six steps, respectively. Their low
      cytotoxicity, high stability in plasma and, in the case of 11, efficient
      hydrolysis in the presence of alpha-galactosidase, fulfill preliminary conditions
      for their use in combination with monoclonal antibody-enzyme conjugates.

PMID- 7575990
TI  - Effects of interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF
      alpha) association in intraperitoneal radioimmunotherapy: studies on an in vitro
      micrometastasis model.
AB  - We considered the usefulness of an association of two cytokines interferon gamma
      (INF gamma) and tumor necrosis factor alpha (TNF alpha) in optimizing
      intraperitoneal (i.p.) radioimmunotherapy of ovarian cancer. Studies were
      performed in conditions similar to those observed in vivo, using tumor multicell
      spheroids of the SHIN-3 ovarian adenocarcinoma line which expresses CA125 and O3
      antigens. Light and electron microscopy showed that this cytokine association
      caused considerable modification of the three-dimensional morphology of the
      spheroids and the cells composing them. The uptake and retention kinetics of 125I
      labeled F(ab')2 fragments of OC125 and OVTL-3 antibodies indicated that the
      presence of the cytokines led to a 1.5-fold increase in the quantity of O3
      antigen at the spheroid surface. These results were confirmed by autoradiographs
      showing that the INF gamma-TNF alpha association produced extensive direct
      antitumor action, with better penetration and uptake of OVTL-3 antibody. Thus,
      i.p. radioimmunotherapy of micrometastases could be optimized by an initial
      injection of the IFN gamma-TNF alpha combination.

PMID- 7575991
TI  - Novel potent inhibitors of the DNA repair enzyme poly(ADP-ribose)polymerase
      (PARP).

PMID- 7575992
TI  - Antigen presentation in the pathogenesis of autoimmune endocrine disease.

PMID- 7575993
TI  - On the issue of inappropriate HLA class II expression on endocrine cells: an
      answer to a sceptic.

PMID- 7575994
TI  - Pancreatic lymph nodes are early targets of T cells during adoptive transfer of
      diabetes in NOD mice.
AB  - The circulation pathway of diabetogenic T lymphocytes prior to insulitis was
      investigated using adoptive transfer of diabetes in the non-obese diabetic (NOD)
      mouse model. Transferred T cells were distinguished from recipient T cells using
      two strains of mice congenic at the Thy1 locus. They were monitored in the
      pancreas and in several lymphoid organs including thymus, spleen, and lymph nodes
      from pancreatic, mesenteric, axillary, inguinal and lomboaortic areas, from Day 0
      to Day 15 after the adoptive lymphocytic transfer. Immunohistochemical studies
      showed that at Day 2 post-transfer the pancreatic lymph nodes (PLN) and to a
      lesser extent the spleen, are the first two organs to be infiltrated. The amount
      of T cells of donor origin using quantitative flow cytometric analysis was 4% and
      2.6% respectively. This percentage increased to 19% in the PLN at Day 15 and did
      not exceed 7% in the spleen. Analysis of the expression of IL-2 receptor present
      at the surface of activated T lymphocytes showed that 73% of donor T cells were
      activated in the PLN within 3 days post-transfer in contrast to 0% in the spleen.
      The accumulation and activation of T cells in the PLN may imply a role of these
      lymphoid organs in harbouring the diabetogenic T cells during the early steps of
      the disease.

PMID- 7575995
TI  - Analysis of action mechanism of lymphotoxin in prevention of cyclophosphamide
      induced diabetes in NOD mice.
AB  - Recently we reported that lymphotoxin (LT) administration protected non-obese
      diabetic (NOD) mice and BB rats from insulin-dependent diabetes mellitus. In this
      study we analysed the protection mechanism of LT by using cyclophosphamide (CY)
      induced autoimmune diabetes in NOD mice. Pre-administration of 500 or 1000 U of
      LT three times a week between the age of 4 and 11-13 weeks before CY-treatment
      strongly inhibited CY-induced diabetes. This inhibition was reproduced by LT pre
      administration at an earlier age (4 to 7 weeks) but not at a later age (8 to 11
      or 10 to 12 wks). LT post-administration (100 U daily or 500 U twice a week)
      after CY-treatment at 14 weeks of age also strongly inhibited CY-induced
      diabetes. Spleen cell transfer was carried out using various combinations of
      donors and recipients. Spleen cell transfer from the non-diabetic mice, which
      were LT pre-administered between the age of 4 and 13 wks, to CY-treated mice did
      not significantly inhibit CY-induced diabetes, while transfer of the cells from
      the similarly treated mice to irradiated recipients did induce diabetes although
      the onset of diabetes was significantly delayed. Diabetes was not transferred by
      spleen cells from diabetic mice to LT pre-administered and CY-treated mice. LT
      administration did not change subpopulations and adhesion molecule expressions of
      the spleen lymphocyte. Taken together, these results suggest that LT protects NOD
      mice from CY-induced diabetes by making the mice resistant to autoimmune diabetes
      and possibly by suppressing anti-islet effector cells, but not by inducing
      adoptively transferable suppressor cells, although the precise mechanisms still
      remain to be elucidated.

PMID- 7575997
TI  - Tumor necrosis factor mediates the protective effect of Freund's adjuvant against
      autoimmune diabetes in BB rats.
AB  - In previous studies we reported that a single injection of complete Freund's
      adjuvant (CFA) in early life inhibits the development of autoimmune diabetes in
      BB diabetes-prone (DP) rats, and that CFA upregulates tumor necrosis factor-alpha
      (TNF alpha) production by macrophages of DP rats. In this study, we asked if CFA
      induced prevention of diabetes in DP rats might be mediated by TNF alpha. Chronic
      intraperitoneal injection of TNF alpha, 20 micrograms daily from age 50 to 110
      days, significantly decreased diabetes incidence in DP rats from 83% (15 of 18)
      to 37% (seven of 19) at age 110 days. Similarly, a single intraperitoneal
      injection of CFA, 100 microliters at age 26 days, significantly decreased
      diabetes incidence from 80% (16 of 20) to 50% (10 of 20) at age 110 days.
      Prevention by either TNF alpha or CFA was associated with decreased insulitis and
      preservation of islet beta-cells. By contrast, treatment of DP rats with CFA,
      plus antiserum to TNF alpha three times a week from age 26 to 110 days, obviated
      CFA-induced protection against beta-cell destructive insulitis and diabetes.
      Thus, diabetes incidence was 75% (18 of 24) in DP rats treated with CFA plus anti
      TNF alpha antiserum, similar to that in untreated DP rats (80%), but only 44%
      (eight of 18) in DP rats treated with CFA plus control serum, similar to that in
      DP rats with CFA alone (50%). These results suggest that TNF alpha may be a
      mediator of the protective effects of CFA against autoimmune diabetes development
      in BB rats.

PMID- 7575998
TI  - IdLNF1-specific T cell clones accelerate the production of IdLNF1 + IgG and
      nephritis in SNF1 mice.
AB  - We have shown that antibodies bearing a nephritogenic idiotype (IdLNF1) are
      important in the pathogenesis of autoimmune glomerulonephritis in the (NZB x
      SWR)F1 hybrid, SNF1. A significant shift in the ratio of CD4+ to CD8+ IdLNF1
      specific T lymphocytes, in favour of CD4+ IdLNF1-specific T cells, occurred at 22
      24 weeks of age in the SNF1 and correlated with an increase in serum IdLNF1 + IgG
      and its deposition in the kidney. Recently, we reported the characteristics of
      six IdLNF1-specific T cell clones (CD3+CD4+CD8-V beta 17a+) derived from 22-week
      old SNF1 mice which proliferated in response to IdLNF1 + Ig and augmented IdLNF1
      + IgG production when mixed with SNF1 B cells in vitro. No increase in the
      production of anti-DNA antibodies was seen. Here we report results of the
      adoptive transfer of three of these clones, A1, B6 and D2, into 6-8-week-old SNF1
      mice. Serum immunoglobulin (Ig) (IgG and IgM) levels did not differ from those of
      age-matched unmanipulated SNF1 up to and including 35 days post-injection.
      Similarly, total IdLNF1 + Ig levels did not vary significantly among the groups
      until 28 days post-injection. However, elevated levels of IdLNF1 + IgG were
      observed as early as 7 days post-injection in mice receiving clone B6 and 21 days
      post-injection in mice receiving clone D2. This was in sharp contrast with the
      results obtained in mice treated with clone A1 or unmanipulated SNF1 mice, which
      did not express IdLNF1 + IgG during this period. Digital image analysis of the
      kidney glomeruli of mice receiving T cell clones B6 or D2 demonstrated a
      significantly (P < 0.05) higher level of IdLNF1 + Ig deposition and
      glomerulonephritis than age-matched unmanipulated SNF1 mice or mice which had
      received clone A1. Interestingly, there was no statistically significant
      difference in the production of anti-ssDNA or dsDNA antibodies with the
      treatments. Mean survival for mice treated with T cell clones B6 and D2 was
      significantly (P < or = 1 x 10(-6)) shorter compared to unmanipulated SNF1 mice,
      while that of mice which had received T cell clone A1 was significantly (P < or =
      3 x 10(-6)) longer, as determined by chi-squared analysis. The overall survival
      of mice treated with clones B6 and D2 did not differ from that of unmanipulated
      mice; however, mice treated with clone A1 survived significantly (P < or = 0.05)
      longer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7575996
TI  - Specific destruction of islet transplants in NOD<-->C57BL/6 and NOD<-->C3H/Tif
      embryo aggregation chimeras irrespective of allelic differences in beta-cell
      antigens.
AB  - We have tested the hypothesis that allelic differences in the antigens expressed
      by the beta-cells of the islets of Langerhans influence the development of
      insulitis in the non-obese diabetic (NOD) mouse. Islets of Langerhans from NOD,
      C57BL/6 and C3H/Tif mice were transplanted under the kidney capsule of NOD<-
      >C57BL/6 and NOD<-->C3H/Tif embryo aggregation (EA) chimeras and the infiltration
      was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets
      was observed in 60% of the NOD<-->C57BL/6 and in 55% of the NOD<-->C3H/Tif EA
      chimeras. All transplanted EA chimeras that developed insulitis also displayed
      mononuclear cell infiltrates in the transplants, irrespective of the origin of
      the transplanted islets. In contrast, no infiltration of transplants was detected
      in EA chimeras scoring negative for insulitis. These results demonstrate that the
      specific destruction of islet transplants does not require the expression of NOD
      specific antigens by the islets. Moreover, the beta-cell destruction appears not
      to be restricted to NOD-MHC. The correlation between insulitis and transplant
      beta-cell destruction suggests the possibility that the development of insulitis
      is a prerequisite for transplant specific destruction. MHC restricted destruction
      may, therefore, precede the beta-cell destruction of transplanted islets. The
      chimerism among the mononuclear cells infiltrating the islet transplants was
      found to correlate with the overall haematopoetic chimerism in each of the
      individual EA chimeras. This observation suggests that NOD bone marrow, as well
      as non-NOD bone marrow, generates cells contributing to the beta-cell destruction
      process.

PMID- 7576000
TI  - Lack of requirement for CD8+ cells in recovery from and resistance to
      experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a model of T-cell mediated
      autoimmune disease. Active disease is mediated by myelin basic protein specific
      CD4+ T-cells, whose adoptive transfer can also induce passive disease. In the
      Lewis rat EAE is a transient disease inducing lasting resistance to rechallenge.
      The mechanisms of recovery and resistance are poorly understood. CD8+ suppressor
      T-cells have mostly been thought to be central, especially in resistance to
      reinduction of the disease. In this study we showed by complete depletion of CD8+
      cells that this subset does not influence either recovery or resistance to EAE in
      the Lewis rat. This was further confirmed by depleting CD8+ cells only after
      recovery from acute EAE. Such depletion did not diminish the effective resistance
      to rechallenge. Recovery from and resistance to EAE appear not to require the
      presence of CD8+ cells.

PMID- 7575999
TI  - Dietary omega-3 lipids delay the onset and progression of autoimmune lupus
      nephritis by inhibiting transforming growth factor beta mRNA and protein
      expression.
AB  - The present study was carried out to test whether transforming growth factor beta
      (TGF beta) plays a pathological role in the induction or progression of
      glomerulonephritis in a murine model of systemic lupus erythematosus (SLE), and
      whether dietary supplementation with fish oil (FO) can modulate the expression of
      TGF beta. Weanling female (NZB x NZW) F1 (B/W) mice were divided into three
      groups. One group was fed an unmanipulated diet (lab. chow; LC) and the other two
      groups were fed a nutritionally adequate semipurified diet supplemented with 10%
      CO or FO. Both water and food were provided ad libitum. Proteinuria and serum
      anti-dsDNA antibody levels were measured to assess disease progression. Mice were
      killed at 3.5 and 6.5 months of age and renal mRNA levels for TGF beta isoforms,
      fibronectin-1 (FN-1) and intercellular adhesion molecule-1 (ICAM-1) were studied
      by Northern blot analysis. TGF beta 1 protein levels were also examined in
      kidneys by Western blot analysis. Our results indicate that at 3.5 months of age,
      when urinary protein levels were undetectable and very low levels of anti-dsDNA
      were detected, no mRNA signal could be detected for TGF beta isoforms, ICAM-1 and
      FN-1 in either dietary group. However, at 6.5 months, the FO-fed mice, compared
      to LC and CO, had [1] greatly reduced proteinuria (LC: 2-3+, CO: 2-3+; FO: trace 
      1+) and serum anti-dsDNA antibodies; [2] improved survival (CO: 100% death
      (15/15) occurred by 8 months; FO: 50% were alive at 12 months (8/15) and [3]
      reduced renal TGF beta 1 mRNA and protein levels. TGF beta 2 and beta 3 were not
      significantly affected by FO diet. Similarly, lower levels of renal FN-1 and ICAM
      1 mRNA were observed in FO fed mice. These data indicate that in B/W mice on a FO
      diet, prolonged survival and amelioration of renal disease may be attributed at
      least in part to lower levels of TGF beta 1 mRNA and protein in the kidneys.

PMID- 7576001
TI  - Variable region-connected, dimeric fraction of intravenous immunoglobulin
      enriched in natural autoantibodies.
AB  - The beneficial effect of intravenous immunoglobulin (IVIg) therapy in patients
      with autoimmune diseases is at least partially dependent on the content in IVIg
      of antibodies capable of interacting with variable regions (idiotypes) of
      autoantibodies. In the present study, we have evaluated the antibody activity to
      a panel of self and environmental antigens of IVIg preparations and their dimer
      enriched fractions. Dimers were either obtained by affinity chromatography of
      IVIg on Sepharose-bound F(ab')2 fragments of IVIg or by size exclusion gel
      filtration chromatography of IVIg. Enrichment of IVIg in dimers was found to be
      associated with an increase in the antibody activity against self-antigens as
      compared with unchromatographed IVIg. Our findings extend previous observations
      on enhanced autoantibody content of the affinity chromatography-separated
      'connected' fraction of IVIg and suggest that therapeutic preparations of IVIg
      enriched in dimers may be obtained by size exclusion chromatography. Separation
      by size increases the feasibility of industrial-scale preparation of IVIg with
      high dimer content that are endowed with high potential immunomodulatory activity
      in vivo.

PMID- 7576002
TI  - Autoantibody profile in the sera of women with hyperprolactinemia.
AB  - Prolactin (PRL) has been implicated as an important in vivo modulator of cellular
      and humoral immunity. In order to elucidate the impact of elevated serum PRL
      levels on the immune system, we measured circulating autoantibodies in the serum
      of 33 hyperprolactinemic (HPRL) women and in 19 healthy women with normal PRL
      levels. All sera were examined for the presence of autoantibodies against 15
      different antigens, including: ssDNA, dsDNA, histones (H2AH2B), Sm, RNP, SS-A/Ro,
      SS-B/La, cardiolipin, Scl-70, Jo1, collagen, glomerular basement membrane (GBM),
      pyruvate dehydrogenase (PDH), proteinase-3 (PR3) and MPO. Twenty-five of 33
      (75.7%) HPRL women were found to have at least one autoantibody, while none of
      the 19 women with normal PRL had any. Eight HPRL women had seven or more (up to
      nine) different autoantibodies. Some of the autoantibodies were more frequently
      expressed than others, namely: anti-ss-DNA, anti-dsDNA, anti-Sm, anti-PDH and
      anti-SS-A/Ro. Autoantibodies to the autoantigens tested are common in a variety
      of autoimmune and rheumatic disorders including systemic lupus erythematosus
      (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma,
      primary biliary cirrhosis (PBC), polymyositis/dermatomyositis and vasculitis. Yet
      none of the HPRL women whose serum was found to contain high titers of
      autoantibodies presented with symptoms related to the respective autoimmune
      disorders. Our results support the role of PRL in the regulation of immune
      responses in man.

PMID- 7576003
TI  - HLA-DP and susceptibility to insulin-dependent diabetes mellitus in an ethnically
      mixed population. Associations with other HLA-alleles.
AB  - It is known that certain combinations of alleles within the Human Leukocyte
      Antigen (HLA) Complex are associated with susceptibility or resistance to insulin
      dependent diabetes mellitus (IDDM). The association of DR and DQ with IDDM has
      been well documented. Even though the association of specific DP alleles with
      some autoimmune diseases (i.e. juvenile rheumatoid arthritis [JRA] and celiac
      disease) has already been demonstrated, the role of HLA-DP genes in IDDM remains
      uncertain. A previous study conducted on a group of diabetic Venezuelan families
      with IDDM proband demonstrated that the HLA-DRB1*04-DQA1*03-DQB1*0302 and DRB1*03
      DQA1*0501-DQB1*0201 combinations present a strong association with susceptibility
      to IDDM. The availability of this population enabled us to assess further
      susceptibility associated with other HLA class II alleles. We analysed HLA-DPA1
      and DPB1 genes of 42 Venezuelan families with one IDDM proband and of 32 healthy
      families by oligotyping (PCR-SSO) using primers and probes from the XIth
      Histocompatibility Workshop. In contrast with previous data reported in other
      populations, the HLA DPA1*01-DPB1*0202 was the only haplotype significantly
      associated with IDDM in the Venezuelan population studied. In most cases the data
      showed this HLA DP allele combination as a part of the HLA DRB1*03-DQA1*0501
      DQB1*0201 haplotype positively associated with IDDM, indicating a linkage
      disequilibrium between the alleles involved in this HLA DR-DQ-DP haplotype and as
      a consequence, a secondary role of HLA-DP genes in conferring susceptibility to
      the development of the disease. The analysis also indicates a non-significant
      increase of HLA DPA1*01-DPB1*0301 and DPA1*02-DPB1*1301 haplotypes among
      diabetics. However, both combinations were in 50% of the cases associated with
      the HLA DRB1*04-DQA1*03-DQB1*0302 haplotype. These data and their comparison with
      HLA DR-DQ-DP haplotypes in more homogeneous ethnic groups support the existence
      of a weak association of IDDM with specific HLA DP alleles and indicate how the
      distribution of these DP alleles could differ depending on the ethnic groups
      studied.

PMID- 7576004
TI  - Myo-inositol monophosphatase: diverse effects of lithium, carbamazepine, and
      valproate.
AB  - The therapeutic molecular sites of action for the mood-stabilizing medications
      are unknown. Myo-inositol monophosphatase (E.C. 3.1.3.25) is a major enzyme of
      the inositol signaling system that has previously been shown to be inhibited by
      clinically relevant concentrations of lithium, implicating this enzyme as a
      potential therapeutic site of action in manic-depressive disorder. Inhibition of
      myo-inositol monophosphatase (IMPase), which converts myo-inositol monophosphates
      to myo-inositol, results in increased levels of myo-inositol monophosphates and
      decreased myo-inositol available for the resynthesis of inositol phospholipids.
      In addition to lithium, carbamazepine and valproate are also used medically to
      treat manic-depressive disorder. It is of considerable interest to determine
      whether inhibition of IMPase activity is a common unifying mechanism for mood
      stabilizing medications. Using a partially purified myo-inositol monophosphatase
      preparation derived from bovine brain, we examined the effects of lithium,
      carbamazepine, and valproate on the IMPase reaction. These results demonstrate
      that (1) lithium inhibited IMPase activity in the low millimolar range, (2)
      carbamazepine stimulated the IMPase reaction beginning in the low-micromolar
      range, and (3) valproate did not demonstrate any stimulation or inhibition of
      IMPase. We conclude that inhibition of IMPase is not a common neurochemical
      mechanism for mood-stabilizing medications.

PMID- 7576005
TI  - Simultaneous increases of extracellular monoamines in microdialysates from
      hypothalamus of conscious rats by duloxetine, a dual serotonin and norepinephrine
      uptake inhibitor.
AB  - Duloxetine (LY248686, [+]-N-methyl-3-(1-napthalenyloxy)-2-thiophene-propanamine)
      is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and
      norepinephrine (NE) uptake in hypothalamus and cerebral cortex of rat brain (Wong
      et al. 1993; Fuller et al. 1994). Consistent with the dual mechanisms of
      inhibiting 5-HT and NE uptake, duloxetine at 15 mg/kg IP produced large increases
      in extracellular levels of 5-HT (250%) and NE (1,100%) 30 minutes after systemic
      administration. Levels of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and 5
      hydroxyindoleacetic acid (5-HIAA), metabolites of NE and 5-HT, respectively, were
      reduced, whereas those of dopamine (DA) and its metabolite 3, 4
      dihydroxyphenylacetic acid (DOPAC) were not significantly altered. Duloxetine at
      7 mg/kg produced less pronounced increases while no consistent effects were
      observed at 4 mg/kg. In this dose range, duloxetine inhibited 5-HT uptake in
      platelets ex vivo without inhibiting striatal dopamine (DA) uptake. In the
      present study we also found that the primary amine (a racemate) of duloxetine is
      about one-fourth as active as duloxetine to inhibit 5-HT and NE uptake. The
      potential primary amine metabolite of duloxetine might contribute, in part, to
      the inhibition of 5-HT and NE uptake in vivo. Thus the ability to produce robust
      increases of extracellular 5-HT and NE levels suggests that duloxetine may
      potentially be a highly effective antidepressant agent.

PMID- 7576006
TI  - Neurochemical and physiological effects of cocaine oscillate with sequential drug
      treatment: possibly a major factor in drug variability.
AB  - Variability in response to drug treatment is a poorly understood problem with
      severe consequences for both the individual and the health care delivery system.
      Our data suggest that one source of variability may be inherent in the way
      physiological systems normally respond to repeated drug exposures. We report that
      for a wide array of endpoints-amphetamine-evoked, in vitro striatal dopamine
      efflux, amphetamine and K(+)-evoked efflux of heart norepinephrine and nonevoked
      plasma levels of corticosterone and glucose-repeated, in vivo cocaine (15 mg/kg
      IP) administration to male rats precipitated successive oscillations in the
      magnitude or direction of the organism's responsiveness to subsequent cocaine
      administration. This capacity of cocaine to produce oscillations in response to
      successive administrations appears to be due to its foreign/stressful aspect
      rather than its specific pharmacological properties.

PMID- 7576007
TI  - Application of a novel fiber-optic biosensor in situ to investigate the metabolic
      effect of lactate infusion.
AB  - Recently developed biosensor technology, which allows near real-time measurement
      in situ of gas tension (pCO2 and pO2) and of pH, was applied to arterial blood,
      cerebrospinal fluid (CSF), and brain parenchyma during intravenous lactate
      infusion in monkeys. Comparison of simultaneous biosensor measurements and
      discrete arterial blood sampling for traditional blood gas analyses indicated a
      high level of correlation for pCO2, pO2, and pH. Arterial pO2 and pH values were
      significantly higher and pCO2 significantly lower than corresponding CSF and
      brain parenchyma values at baseline, during and following lactate infusion. There
      was a divergence between arterial and brain parenchyma pH and pO2 measurements.
      Lactate infusion was associated with progressive arterial pH rises, consistent
      with the production of a metabolic alkalosis. Cerebrospinal fluid pCO2 remained
      unchanged during and following lactate infusion. Brain parenchyma exhibited a
      complex pattern of response characterized by a trend for pO2 and pH to decrease
      during lactate infusion, which reversed following completion of the infusion.
      These observations are suggestive of a transient hypoxia from decreased cerebral
      blood flow and/or reduced oxyhemoglobin dissociation during lactate infusion, but
      verification of these results is required.

PMID- 7576008
TI  - Platelet binding characteristics distinguish placebo responders from
      nonresponders in depression.
AB  - To determine whether there are characteristics distinguishing placebo responders
      from nonresponders, we studied 37 outpatients meeting DSM-III-R criteria for
      depression who were enrolled in controlled drug trials and 14 control subjects.
      Clinical data and blood samples were collected on admission and after a 7- to 10
      day placebo washout. All patients experiencing a 40% drop in the Hamilton Rating
      Scale for Depression (HRSD) at the time of the second evaluation were considered
      placebo responders. There were no statistically significant differences between
      the two groups in clinical variables. Platelet markers distinguished the groups:
      Most notably, placebo nonresponders had the lowest 5-HT uptake site density
      values, placebo responders had intermediate values, and normal controls had the
      highest values. Placebo responders and placebo nonresponders had higher 5-HT
      uptake affinity values. No significant differences were observed among the groups
      in platelet 5-HT2 receptor site density or affinity values. These results suggest
      that platelet serotonin characteristics, but not common clinical characteristics,
      may distinguish depressed patients who do and do not respond to placebo.

PMID- 7576009
TI  - Metabolism of clomipramine in a Japanese psychiatric population: hydroxylation,
      desmethylation, and glucuronidation.
AB  - We measured the concentrations of clomipramine and its metabolites, N
      desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine
      by high-performance liquid chromatography in 108 Japanese psychiatric patients
      receiving clomipramine hydrochloride PO. The concentrations of the glucuronide
      conjugates of 8-hydroxyclomipramine and 8-hydroxy-N-desmethylclomipramine were
      assayed via enzymatic hydrolysis. Although there were large interindividual
      variations of concentrations of parent, intermediate metabolic compounds, and
      glucuronide conjugates, significant positive correlations were observed between
      these drug concentrations and daily doses of clomipramine hydrochloride (mg/kg
      body weight). Although the metabolic ratios for desmethylation, hydroxylation,
      and glucuronidation that were calculated from steady-state drug concentrations
      varied substantially with 36-, 14-, and 28-fold interindividual variations,
      respectively, apparent poor desmethylators, poor hydroxylators, or poor
      glucuronidators were not found.

PMID- 7576010
TI  - Lack of discrimination by agonists for D2 and D3 dopamine receptors.
AB  - The affinities of D3 dopamine receptors for antagonists are similar to those of
      D2 receptors. D3 receptors have been reported, however, to have affinities nearly
      100-fold higher than those of D2 receptors for some agonists, including (+/-)-7
      hydroxy-n,n-dipropyl-aminotetralin (7-OH-DPAT) and quinpirole. This has led to
      the use of these agonists to try to identify functional responses mediated by D3
      receptors in vivo. However, D2 receptors exist in multiple states having high and
      low affinities for agonists. The G protein-coupled state of D2 receptors is
      believed to be the functional state of these receptors. When receptors were
      labeled with the D2 receptor antagonist [125I]-(S)-3-iodo-N-[(1-ethyl-2
      pyrrolidinyl)methyl]-5,6- dimethoxysalicylamide ([125I]-NCQ-298) under conditions
      that promote uncoupling of receptors from G proteins, the affinities of D3
      receptors were approximately 130-fold higher than those of D2 receptors for 7-OH
      DPAT and quinpirole. When receptors were labeled with the D2 receptor agonist
      [125I]-(R)trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'- propenyl)-amino]tetralin
      ([125I]-7-OH-PIPAT) under conditions that favor interactions of receptors with G
      proteins, the affinities of D3 receptors were less than sevenfold higher than the
      affinities of D2 receptors for the same drugs. Similarly, small differences in
      the affinities of D2 and D3 receptors for other agonists were seen when receptors
      were labeled with [125I]-7-OH-PIPAT. These data demonstrate that putative D3
      receptor-selective agonists also interact with a high-affinity, G protein-coupled
      state of D2 receptors. The similarities in affinities of the agonist-preferring
      state of D2 and D3 receptors means that currently available agonists cannot be
      used to discriminate between behavioral effects mediated by D2 and D3 receptors.

PMID- 7576011
TI  - alpha 2 adrenergic agonists prevent MK-801 neurotoxicity.
AB  - Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor are
      of considerable interest for various neurotherapeutic purposes, including
      preventing neuronal degeneration in stroke and CNS trauma, suppressing
      neuropathic pain and preventing the development of tolerance to opiate
      analgesics. Unfortunately, NMDA antagonists can cause potentially serious side
      effects, including acute neurodegenerative changes in corticolimbic regions of
      the adult rat brain and psychotic reactions in adult humans. We have been
      investigating the mechanisms underlying the neuropathological changes in rat
      brain and exploring methods of suppressing or preventing such changes. Here we
      report that alpha 2 adrenergic agonists can prevent NMDA antagonist
      neurotoxicity. Therefore, administering alpha 2 adrenergic agonists together with
      NMDA antagonists may be a valuable strategy for preventing adverse side effects
      of NMDA antagonists and making these agents safer for various neurotherapeutic
      purposes.

PMID- 7576012
TI  - Placebo for depression?

PMID- 7576013
TI  - Acute effect of cyclosporin on renal function following the initial changeover to
      a microemulsion formulation in stable kidney transplant patients.
AB  - Potential differences in the acute effect of cyclosporin on renal function when
      dosed orally as the current market formulation or following a milligram-to
      milligram conversion to a new microemulsion formulation were investigated in 14
      stable kidney transplant patients. The study consisted of three sequential
      periods of 2 weeks duration each. Patients entered (period I) and completed
      (period III) the investigation with the market formulation and received the
      microemulsion formulation in period II; individualized cyclosporin doses remained
      unchanged throughout the study. Over one steady-state dosing interval at the end
      of each study period, whole blood cyclosporin pharmacokinetic profiles were
      assessed in parallel with endogenous creatinine clearances over sequential 1- to
      2-h intervals. The rate and extent of cyclosporin absorption were significantly
      greater (P < 0.01) from the microemulsion formulation with average increases of
      73% in peak concentration and 44% in area under the curve compared to the market
      formulation. Sequential creatinine clearances exhibited a transient decrease with
      the nadir occurring on average between 4 and 6 h post dose followed by a rapid
      return to baseline. Specifically in period I on the market formulation,
      clearances decreased from a baseline of 71.7 +/- 20.6 to a minimum of 51.1 +/-
      17.9 ml/min per 1.73 m2 (similar values in period III) and from 76.8 +/- 24.8 to
      53.5 +/- 17.5 ml/min 1.73 m2 in period II on the microemulsion. Neither the
      baseline nor minimum clearances were significantly different among the study
      periods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576014
TI  - Acute phase response after liver transplantation for fulminant hepatic failure
      and cirrhosis.
AB  - The hepatic acute phase response after orthotopic transplantation (OLT) was
      studied in patients with fulminant hepatic failure (FHF) and with cirrhosis, in
      relation to the pre-existing disease. Plasma levels of C-reactive protein (CRP)
      increased significantly on day 1 after OLT in both the FHF (delta = 58
      micrograms/ml) and cirrhosis (delta = 94 micrograms/ml) groups and reached a peak
      4-5 days post surgery. alpha 1-Antitrypsin reached normal levels on day 1 post
      transplant and fibrinogen reached normal levels on the 3rd day. The main
      stimulator of acute phase protein synthesis IL-6 was significantly increased pre
      OLT in plasma in both FHF (median 54 pg/ml) and cirrhosis (median 8.7 pg/ml)
      patients compared to controls (2.35 pg/ml, P < 0.05). After OLT, IL-6 decreased
      rapidly in patients with FHF, indicating either removal of the source of IL-6 or
      clearance by the transplanted liver. In patients with cirrhosis, plasma IL-6
      remained low, except in three patients who developed infection/rejection and
      whose IL-6 levels rose above 100 pg/ml. In conclusion, there is a marked acute
      phase response in the liver graft after transplantation, irrespective of the
      aetiology of the liver disease for which the transplant was performed.

PMID- 7576015
TI  - Morphometric image analysis and eosinophil counts in human liver allografts.
AB  - Histology of liver allografts is the gold standard for diagnosis of acute
      cellular rejection. However, scoring the severity of rejection and distinguishing
      it from other infiltrations is not easy. Only one group has evaluated biopsies
      morphometrically and also suggested that eosinophils are a specific diagnostic
      feature. We quantitated eosinophil count in 92 biopsies in a group of 25 patients
      and, in another group of 30 patients, used morphometric image analysis to measure
      the cross-sectional area and cell density in each portal tract in day 5 protocol
      liver biopsies. Rejection was diagnosed by pathological evaluation confirmed with
      clinical and biochemical graft dysfunction graded histologically into mild or
      moderate-to-severe. The control groups were five patients with no rejection, nine
      patients with CMV infection, and eight biopsies in eight patients for whom the
      cause of the liver dysfunction was obscure. The cross-sectional area, the
      inflammatory cell count of each portal tract and the mean portal tract
      inflammatory cell density (cells/mm2) increased with the severity of rejection.
      In each case the regression coefficient was statistically significant.
      Correlating the mean of the total inflammatory cell count with the mean of the
      portal inflammatory cell density (cell/mm2) gave far better separation of the
      mild rejection and moderate-to-severe rejection groups. Eosinophils were specific
      for the presence of acute cellular rejection and increased with the severity of
      rejection. They were absent in the no rejection group, in the CMV group and in
      those with obscure liver dysfunction. The eosinophil count fell markedly
      following treatment of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576016
TI  - Hepatitis C virus infection as a possible risk factor for ductopenic rejection
      (vanishing bile duct syndrome) after liver transplantation.
AB  - Irreversible ductopenic rejection (DR) after orthotopic liver transplantation
      (OLT) is a major cause of late hepatic allograft failure. A variety of risk
      factors for DR have been postulated, but they are controversial. All transplant
      recipients at our institution with graft survival of more than 1 month (n = 120)
      were examined retrospectively with a view to possible risk factors for DR. These
      factors included age, sex, underlying liver disease, hepatitis B and C
      infections, donor-recipient CMV status, post-OLT CMV infections,
      immunosuppressive regimen, ABO blood type, and HLA class I and class II
      mismatches. Statistical analysis was performed with the univariate chi-square
      test or the two-tailed Fischer's exact test. Ten patients (8.3%) developed DR.
      Seventeen patients had HCV infections after OLT. In this group, the incidence of
      DR was highest (4 of 17, or 23.5%). This was significantly higher than for all
      other OLT groups (6 of 103 patients, or 5.8%; P < 0.03). The other factors
      analyzed did not reach statistical significance, including those that other
      authors found important for the development of DR. It may well be that hepatitis
      C infection predisposes one to the development of DR after OLT.

PMID- 7576017
TI  - The flow cytometric detection of alloantibodies in screening for renal
      transplantation.
AB  - Flow cytometric screening of sera using pooled chronic lymphocytic leukaemia
      (CLL) cells has previously been reported as a quick method for detecting HLA
      antibodies of the IgG class. In this study we investigated the sensitivity of
      this method in the detection of IgG and IgM alloantibodies, and its performance
      in serum screening when compared to conventional microlymphocytotoxic screening.
      Results indicate that flow cytometric screening is more sensitive in the
      measurement of IgG alloantibodies by up to five doubling dilutions, whereas the
      converse is true for IgM. IgM autoantibodies were found not to be detectable by
      flow cytometry. By testing a large number of sera by both methods in parallel, we
      have found that a significant proportion of sera exhibiting no activity of IgM
      activity alone on cytotoxic screening contain IgG antibodies detectable with a
      pool of CLL cells on the flow cytometer.

PMID- 7576018
TI  - Effect of blood group and HLA matching on pancreas graft survival with the use of
      UW solution.
AB  - Pancreas graft survival is influenced by various donor and recipient factors.
      Factors that have posed serious problems to pancreas transplantation have
      included the limited cold ischemia time, early graft thrombosis, and rejection. A
      limited cold ischemia time not only causes problems in terms of logistics but
      also implies limitations with regard to HLA matching and organ exchange. Between
      August 1988 and August 1989 we performed a prospective, nonrandomized European
      multicenter study to evaluate the effect of University of Wisconsin (UW) solution
      on pancreas graft survival. In addition, donor and recipient factors were
      collected and their influence on graft survival analyzed. Overall pancreas graft
      survival at 1 and 4 years was 67% and 59%, respectively (n = 62). When only
      simultaneous pancreas and kidney transplants were included, the graft survival
      was 70% and 63% at 1 and 4 years, respectively. The incidence of pancreas graft
      thrombosis was 8%. Cold ischemia time was not found to significantly influence
      pancreas graft survival even when it exceeded 12 h. Factors that did were HLA-DR
      matching, simultaneous pancreas and kidney transplantation versus pancreas
      transplantation alone, and ABO blood group matching. We feel that the use of UW
      solution for pancreas preservation has contributed to improved pancreas graft
      survival and has reduced early graft thrombosis despite much longer cold ischemia
      times of over 12 h. Given this and the significant effect of HLA and blood group
      matching, we conclude that more attention should be paid to preoperative matching
      and organ exchange in order to further improve pancreas graft survival.

PMID- 7576020
TI  - Plasmapheresis as a rescue therapy to resolve cardiac rejection with vasculitis
      and severe heart failure. A report of five cases.
AB  - The predominant causes of late graft loss and death after cardiac transplantation
      are graft rejection and infection. The histopathological classification of acute
      rejection is based on cellular phenomena such as lymphocytic infiltration and
      myocyte damage. The adverse prognostic importance of vascular or humoral
      rejection has been reported, but there is no well-documented treatment available.
      In our experience, comprising 151 orthotopic transplants, five patients presented
      with graft rejection characterized by a lymphocytic vasculitis that did not
      respond to conventional therapy. Because of a deteriorating condition, in spite
      of vigorous antirejection treatment that included inotropic drugs and circulatory
      support. plasmapheresis was tried as a last, desperate means to stop the process
      from developing further. The clinical symptoms rapidly subsided in all five
      patients after the first couple of plasma exchanges. All of the patients are
      alive and well after 2-3.5 years of follow-up. Although the mechanism of action
      is unclear, plasmapheresis was beneficial in these critically ill patients.

PMID- 7576019
TI  - An underlying mechanism for improved liver preservation with a combined histidine
      lactobionate-raffinose flush solution.
AB  - In previous experimental liver transplant studies, it was possible to extend cold
      ischaemic time (CIT) by using a flush/storage solution combining histidine,
      lactobionate and raffinose (HLR). In this study, energy metabolism, glycolytic
      substrate (glucose) and anaerobic end-product (lactate) were examined in rat
      liver over 24 h of cold storage to determine the mechanism of action of the HLR
      solution. In livers subjected to simple flush and storage with the HLR solution,
      levels of ATP and ADP were considerably higher than livers stored with modified
      UW throughout 24 h of storage; at 4 h of storage, ATP and ADP levels were 1.1 and
      3.1 mumol/g for HLR solution versus 0.18 and 0.81 mumol/g for UW solution. Total
      adenylate contents (TA = ATP + ADP + AMP) also remained 1-2 mumol/g higher in HLR
      treated livers than those preserved in UW; TA values ranged from 3.8 to 5.7
      mumol/g. Glucose increased to 20-35 mumol/g by 10-24 h of storage (similar to the
      UW group). Lactate rose to almost twice that in livers stored in UW; total
      lactate accumulation was approximately 10.0 mumol/g. This study demonstrated that
      the combined HLR solution is able to prolong the maximum 'safe' CIT by increasing
      anaerobic metabolism and consequently preserving liver energetics. The second
      part of the experiment examined the effect of continuous perfusion (with/without
      O2) over the 1st h of cold ischaemia. Under current methods of liver flushing and
      excision, the 1st h of cold storage may be the critical time of metabolic
      'adjustment' since most of the pH and ATP changes occur during this
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576021
TI  - The incidence and management of biliary complications following liver
      transplantation in children.
AB  - Biliary complications following liver transplantation are a cause of significant
      morbidity and mortality. During the period 1988-1993 ten cases of biliary
      complications occurred after 98 transplantations in 78 children. The
      complications were four bile leaks, three intrahepatic biliary strictures (one
      with recurrent cholangitis), two anastomotic biliary strictures (one with
      recurrent cholangitis) and one recurrent cholangitis. All leaks occurred within 6
      weeks of transplantation whereas all strictures and cholangitic episodes occurred
      after 3 months. Two biliary complications (20%) - one intrahepatic and one
      anastomotic stricture - developed secondary to hepatic artery thrombosis. The
      incidence of biliary complications was 13.2% with whole liver grafts as compared
      to 6.7% with partial liver grafts and it was 4.3% with duct-to-duct anastomosis
      as compared to 12.0% with Roux-en-Y hepatico-jejunostomy. Seven children required
      intervention for management of biliary complications and three were managed
      conservatively. There were no deaths related to the biliary complications.

PMID- 7576022
TI  - Developing the ideal immunosuppressive protocol by internal audit.
AB  - To identify the best immunosuppressive protocol in a centre where five different
      regimens are employed, 227 consecutive renal recipients who were transplanted
      over a 2.5-year period were studied. The five different regimens employed were
      cyclosporin monotherapy, dual therapy (cyclosporin and prednisolone), triple
      therapy (cyclosporin, azathioprine, prednisolone), antithymocyte globulin (ATG)
      followed by dual therapy and ATG followed by triple therapy. Recipients were
      chosen for the different regimens according to HLA mismatch, positive donor
      crossmatch due to IgM, regraft and delayed graft function. The group with the
      lowest risk, cyclosporin monotherapy, had the highest acute rejection rate, with
      only 13% free of acute rejection (in comparison to triple immunosuppression, P =
      0.024, chi-square test). The overall infection rate and graft success rate were
      similar between the different groups.

PMID- 7576023
TI  - The role of experimental aluminum intoxication in allogeneic immunoresponse.
AB  - To evaluate the immunological properties of aluminum (Al) in experimental Al
      intoxication in rats, we performed heart transplantation and in vitro
      experiments. Lewis (Lew) rats were intoxicated with intraperitoneal injections of
      AlCl3. heart transplants were performed using Brown-Norway (BN) rats as donors.
      Isotransplants and normal Lew were used as controls. No differences in survival
      were observed. Unidirectional mixed lymphocyte cultures (MLC) and Concanavalin A
      (Con A)-stimulated cultures were prepared using spleen cells from normal and Al
      intoxicated Lew rats. No differences were found in unidirectional MLC.
      Intoxicated cells showed a less intense response to con A than did normal cells.
      In conclusion, we could not detect an immunosuppressive role of Al intoxication
      in experimental cardiac transplantation or in MLC. However, the depressed Con A
      blastogenic response of Al-intoxicated cells may reflect an immunological role
      yet to be defined.

PMID- 7576024
TI  - Central pontine myelinolysis after liver transplantation: a case report.
AB  - A patient development deteriorating mental status, quadriparesis, and severe
      pseudobulbar palsy with the inability to speak or swallow following orthotopic
      liver transplantation (OLT). Subsequently, abnormalities were found in the pons
      on MRI that were consistent with central pontine myelinolysis (CPM). Marked
      recovery occurred following transfer to the rehabilitation medicine service.
      Seven months following development of CPM, a mild dysarthria has persisted, but
      full ambulation has returned. Although no significant fluctuations in serum
      sodium were seen perioperatively, multiple risk factors associated with the
      development of CPM were present, including end-stage liver disease, a history of
      alcohol abuse, malnutrition, hypoxia, and use of cyclosporin medication
      postoperatively. This case demonstrates that the development of CPM may occur
      following OLT despite meticulous attention to serum sodium concentrations. We
      conclude that CPM is multifactorial in nature. There can be a great variation in
      its clinical course.

PMID- 7576025
TI  - Donor-related secondary haemorrhage complicating renal transplantation.
AB  - We report two cases of secondary haemorrhage in renal transplant recipients that
      would appear to relate to their common donor. Our experience confirms the
      inadequacy of arterial repair in this setting. One patient, a middle aged
      diabetic male, required excision of his external iliac artery, but recovered
      without reconstructive surgery. In the second case nephrectomy was performed on
      day 8 because of accelerated rejection. This was followed by recurrent sepsis due
      to E. coli, which was implicated in the previous case. Haemorrhage from the donor
      aortic wall patch occurred 3 weeks later. We now recommend that if secondary
      haemorrhage occurs, recipients of other organs from the donor should be carefully
      monitored for evidence of infection. If this is found and a similar organism
      cultured, consideration to transplant nephrectomy should be made with removal of
      all donor tissue to avoid the risk of subsequent secondary haemorrhage.

PMID- 7576027
TI  - A technique for vascular reconstruction of pancreaticoduodenal allograft. A
      literature review and case report.
AB  - In most cases, whole pancreaticoduodenal allograft vessels can be reconstructed
      using a segment of donor common iliac artery bifurcation. An alternative way to
      bridge the splenic artery and the superior mesenteric artery (SMA) is to use a
      short segment of distal SMA as an interposition graft, as described herein.

PMID- 7576026
TI  - Preservation of renal perfusion and postoperative renal function by side-to-side
      cavo-caval anastomosis in liver transplant recipients.
AB  - Postoperative renal failure is common after liver transplantation (LT). The aim
      of this study was to investigate peroperative renal perfusion and postoperative
      renal function in 12 patients who underwent LT with side-to-side cavo-caval
      anastomosis (SSCCA). Three phases were considered during the procedure:
      hepatectomy, the anhepatic phase, and the postreperfusion phase (phases 1, 2, and
      3, respectively). Mean arterial pressure, IVC pressure, and renal perfusion
      pressure were significantly higher during phase 2 than during phases 1 and 3.
      Cardiac index and pulmonary capillary wedge pressure did not differ significantly
      during the three phases. Creatinine clearance did not significantly decrease
      postoperatively. We conclude that SSCCA is associated with both the preservation
      of renal perfusion pressure during the entire procedure and the preservation of
      postoperative creatinine clearance. It is, moreover, a technique that results in
      a low rate of postoperative renal failure after LT.

PMID- 7576028
TI  - Alternative procedure for failed reconstruction of a right replaced hepatic
      artery in liver transplantation.
AB  - A right replaced hepatic artery (RRHA) arising from the superior mesenteric
      artery (SMA) is the most frequent variation of the hepatic arterial supply
      requiring backtable reconstruction. There are several widely used techniques for
      backtable reconstruction of the RRHA to a single conduit. If these
      reconstructions fail, due to technical reasons or size discrepancies, an
      alternative method of rearterialization is needed. We describe six cases in which
      an RRHA was anastomosed to the donor's gastroduodenal artery (GDA) stump
      utilizing a loupe magnification technique. In four cases the reconstruction was
      performed at the time of the backtable procedure and in two after reperfusion and
      failure of the original RRHA to splenic artery (SA) reconstruction. In all cases,
      the anastomoses remained patent. All patients had Doppler sonography and two had
      subsequent arteriograms that verified anastomotic patency. This method of
      reconstruction is more demanding technically but obviates the awkward 90-degree
      twist of the hepatic artery when an RRHA is anastomosed to the SA stump.

PMID- 7576029
TI  - Allogenic vascularized transplantation of a human femoral diaphysis under
      cyclosporin A immunosuppression.

PMID- 7576032
TI  - Enhancement of CTL response induced by a viral peptide using cationized BSA, a
      Th1-stimulating adjuvant.
AB  - We have recently shown that it is possible to activate cytotoxic T cells (CTL) in
      vivo with HSV-1 glycoprotein B H-2Kb-restricted peptide (gB peptide) independent
      of CD4+ T cell help. Here we report that the gB peptide-specific CTL response is
      significantly enhanced when mice are immunized with a mixture of gB peptide and
      cationized BSA (cBSA). The latter molecule is a positively charged form of the
      native BSA molecule that stimulates CD4+ T cells to produce cytokines
      characteristic of Th1 cells. The cBSA-enhanced CTL response required the presence
      of CD4+ T cells, but it did not require stimulation in vitro by antigen or
      exogenous cytokines. gB peptide/cBSA-activated LN cells transcribed IL-2 and IFN
      gamma, but only IL-2 was essential for CTL development. Our data demonstrate that
      while activation of CTL may occur in the absence of CD4+ cells, cytokines
      produced by CD4+ Th1 cells provide stimulatory signals during CTL maturation.
      Thus, cotreatment with a substance that activates Th1 CD4+ cells may be useful
      for achieving maximal CTL responsiveness.

PMID- 7576034
TI  - Serum reactivity against an immunoregulatory sequence of HIV p24 in HIV-1
      infected subjects.
AB  - The aim of this study was to assess the antibody reactivity in HIV-infected
      subjects against an HIV-1 p24 sequence, p226 (aa226-237), including a seven amino
      acid epitope showing immunosuppressive activity in vitro and to evaluate the
      relationship between anti-peptide antibody levels and disease progression. Sera
      of HIV-infected subjects, at different stages of disease, were compared to
      control sera in a retrospective evaluation. Recombinant HIV-1 p24 and p24- and
      control-peptides were used in an enzyme immunoassay as targets for antibodies
      present in the sera. Antibodies directed against the whole p24 protein and its
      peptides were found in all the sera studied but at different levels. The anti
      p226 reactivity was not significantly different at different clinical stages.
      Nevertheless, it was inversely correlated to the reactivity directed against the
      whole protein, that was lower in subjects characterized by low CD4 cell numbers.

PMID- 7576033
TI  - Use of helper T cell-inducing peptides from conserved regions in HIV-1 env in a
      noncovalent mixture with a CTL-inducing V3-loop peptide for in vivo induction of
      long-lasting systemic CTL response.
AB  - Our previous reports established that immunization of mice in the footpad with a
      15-amino acid synthetic peptide (R15K) from the V3 loop region in the envelope
      protein gp120 of human immunodeficiency virus type 1 (HIV-1) resulted in rapid
      induction of major histocompatability complex (MHC) class I-restricted, CD8+ HIV
      1 envelope-specific cytotoxic T lymphocytes (CTLs) in the proximal popliteal
      lymph node. While efficient CTL activity could be assayed in lymph node cells for
      8 to 10 weeks after a single injection, spleen cells from these mice showed low
      to negligible levels of specific CTLs at 4 to 8 weeks postimmunization. We tested
      immunizing mice with a noncovalent mixture of a helper T cell (Th) activity
      inducing peptide and R15K and observed efficient induction of R15K-specific CTL
      response that could be assayed up to 8 weeks postimmunization in cells obtained
      from both lymph node and spleen. Efficient CTL priming was observed when Th
      peptides from either of two different conserved regions in the HIV env were mixed
      with R15K, containing a dipalmityl-lysine-glycine-glycine moiety at the amino
      terminus. These data confirm reports in literature describing requirement of Th
      activity for efficient priming of CTL response in vivo. Additionally, these
      studies strongly suggest the possibility of formulating potential vaccine
      candidates consisting of mixtures of synthetic peptides capable of inducing Th
      and CTL responses in the context of multiple MHC haplotypes.

PMID- 7576030
TI  - Endogenous retroviral gp70 genes of the murine lymphoma L5178Y: analysis of
      restriction fragment polymorphism upon induction of drug-mediated immunogenicity.
AB  - Highly immunogenic ("xenogenized") tumor variants appear after treatment of
      murine lymphoma L5178Y with the triazene derivative DTIC, this phenomenon being
      associated with the appearance of structurally abnormal gp70 env proteins in the
      cell variants. In the present study, we have isolated and sequenced several PCR
      amplified gp70 cDNA genes from L5178Y cells. One of the resulting clones was used
      as a probe in Southern and Northern analysis of parental and xenogenized cells.
      The results indicated that xenogenization of tumor cells is associated with
      changes in retroviral env sequences detectable at the genomic level.

PMID- 7576031
TI  - A seroepidemiologic study of HPV infection and incident cervical squamous
      intraepithelial lesions.
AB  - The seroepidemiology of genital human papillomavirus (HPV) and incident cervical
      squamous intraepithelial lesions (SIL) was studied in subjects selected from a
      large cohort monitored for the development of SIL. Serum IgG and IgA responses to
      10 epitopes derived from HPV were measured in 21 incident cases of SIL and 56
      matched controls. Cases showed elevated antibody (i.e., IgG and/or IgA)
      seroprevalence to 245:16, a peptide antigen derived from the E2 open reading
      frame of HPV 16 (OR = 5.76; 95% CI: 1.24, 26.81). The type of HPV DNA detected in
      cervical lavage specimens had no effect on this relationship. Multivariate
      analysis also showed that IgG to 245:6, an analogous peptide derived from HPV 6,
      was negatively associated with SIL (OR = 0.12; 95% CI: 0.02, 0.77). No other
      antibody responses tested were associated with SIL. Furthermore, no antibody
      responses were positively associated with detection of HPV DNA in women without
      SIL. We conclude that incident SIL is positively associated with antibody to an
      epitope derived from the E2 region of HPV 16, and negatively associated with
      antibody to an analogous peptide derived from HPV 6. The seroepidemiology of
      incident SIL appears different from that of cervical HPV infection in the absence
      of SIL.

PMID- 7576035
TI  - Prior infection by respiratory syncytial virus or parainfluenza viruses augments
      virus-specific IgG responses induced by the measles/mumps/rubella vaccine.
AB  - We found previously that immunizing cyclophosphamide-treated mice with one
      Paramyxoviridae virus mixed with dimethyl dioctadecyl ammonium bromide induces T
      cells which apparently also recognize other Paramyxoviridae viruses. This finding
      and the fact that respiratory syncytial virus (RSV) and parainfluenza viruses
      (PIVs) infect children early in life led us to ask if prior RSV or PIV infections
      influence the antibody response to measles and mumps vaccine viruses. Detection
      of virus-specific IgG in serum specimens collected randomly or at defined times
      after measles/mumps/rubella (MMR) vaccination was done with solid-phase enzyme
      immunoassays. The antibody-binding data obtained were converted to serum antibody
      titers by an immunoassay curve-fitting computer program. Prior infection by RSV
      and PIVs correlated with an augmented IgG response not only to measles and mumps
      virus, but also to rubella virus. Furthermore, the augmentation was greater for
      responders below the median response. These data show that common early childhood
      viral infections can influence immunity induced by the MMR vaccine.

PMID- 7576036
TI  - Immunoglobulin-like domain of HIV-1 envelope glycoprotein gp120 encodes putative
      internal image of some common human proteins.
AB  - By examining sequence similarity between the V3-loop of gp120 from various HIV-1
      isolates and human proteins, we found that the V3 loop portion KKGIAIGPGR in
      strain New York 5 (HIV-1NY5) shares 70% identical residues with the collagen-like
      region (CLR) of human complement component C1q-A. C1q CLR was found to react with
      autoantibodies from several autoimmune disorders. Thus, we assumed that it would
      be of interest to find out the C1q reactivity with antibodies from AIDS sera. The
      results obtained show that the V3 loop-derived synthetic peptide KKGIAIGPGRTLY
      reacts both with AIDS patients sera and with antibodies purified on the V3 loop
      peptide-affinity column. The same affinity-purified antibodies bind also to C1q
      molecules. Since, according to our previous results, HIV-1 V3 loops and
      immunoglobulin heavy chain variable regions (Ig VH) share several common
      features, we suggest that the envelope of HIV-1NY5 bears a functional internal
      image of the C1q-A CLR epitope. Therefore, gp120 could manipulate the immune
      network and contribute to HIV-induced autoimmunity.

PMID- 7576037
TI  - Psychiatric screening in geriatric primary care: should it be for depression
      alone?
AB  - Depression in the elderly is highly prevalent, associated with functional
      disability and increased medical costs, and treatable; however, it is
      infrequently recognized and treated. The Agency for Health Care Policy and
      Research has advocated, therefore, increased case-finding efforts for depression
      in primary geriatric care. Anxiety, substance, and somatoform disorders in the
      elderly are similarly prevalent, associated with disability and cost, treatable,
      and also infrequently detected and treated. We believe that psychiatric case
      finding in geriatric primary care should attend to these disorders, therefore, as
      well as to depression. In the present study, we examined whether the association
      between depressive and nondepressive forms of psychopathology was similar in
      geriatric and nongeriatric medical patients. We also examined the relationship
      between each type of pathology and health care utilization and global ratings of
      physical and mental health. In a VA hospital general medical outpatient clinic,
      508 patients completed the SCREENER, which is a brief self-report questionnaire
      that screens for a range of psychiatric disorders, along with a self-report
      questionnaire regarding subjective health and medical care utilization. Of these
      patients, 98% were male, and the median age was 63 years. Patients aged 63 and
      over were compared to younger patients. In both geriatric and younger adult
      patients, we found substantial comorbidity between depressive and nondepressive
      forms of pathology. Moreover, in both age groups, there were significant
      associations between both depressive and nondepressive symptoms and fair-to-poor
      self-rated physical and mental health and increased medical care utilization.
      Approximately half of the cases of nondepressive disorders in the elderly were
      not comorbid with depression, and thus would not have been detected by screening
      for depression alone. Therefore, psychiatric case finding in primary care of
      geriatric males should be directed at anxiety, substance, and somatoform
      disorders, as well as at depression, for treatment resources to be triaged to
      maximally decrease morbidity and cost.

PMID- 7576038
TI  - Study of Alzheimer's dementia patients with parkinsonian features.
AB  - This paper presents a study to test the hypothesis that a parkinsonian subtype of
      Alzheimer's disease exists. Twenty-one patients with dementia of the Alzheimer's
      type (DAT) and coexistent parkinsonian features were matched to 21 DAT control
      patients without parkinsonian signs. All subjects were drawn from 136 patients
      with DAT evaluated between 1980 and 1982. Items from a standardized clinical
      evaluation at the time of diagnosis, from continuous yearly follow-ups, and
      neuropathologic examination were compared to determine if qualitative differences
      exist between the two groups. Those with parkinsonian features had significantly
      shorter duration of symptoms prior to presentation, a trend toward more reports
      of decreased self-care, and more primitive reflexes on physical examination.
      While the total Folstein Mini-Mental State Exam (MMSE) scores at presentation
      were not significantly different, the cases showed greater impairment in language
      and registration subitems. During follow-up, no differences were observed in
      performance on MMSE and Dementia Rating Scale scores. Survival curves showed a
      trend toward poorer survival in the cases. Neuropathologic data were obtained on
      seven patients with both DAT and parkinsonian features and showed three cases
      with Alzheimer's disease (AD) alone and four with AD and Parkinson's disease.
      Four of the DAT control patients were examined neuropathologically, and all had
      AD without evidence of Parkinson's disease. The results provide preliminary
      evidence that Alzheimer's patients with parkinsonian signs are a subtype
      characterized by distinct neurologic signs and a more rapid course.

PMID- 7576040
TI  - The Older Adult Health and Mood Questionnaire: a measure of geriatric depressive
      disorder.
AB  - Depressive disorders are a common problem in late life, requiring consistent and
      reliable screening by clinicians. Such screening should be based upon the most
      recent criteria available to facilitate diagnostic and nosologic agreement. This
      study presents a new screening instrument for geriatric depressive disorders
      based upon DSM-III-R criteria and the known differences in the display of
      depression that occur among older persons. The Older Adult Health and Mood
      Questionnaire (OAHMQ) is a 22-item questionnaire with sound psychometric
      properties and high validity. Its validation included comparisons with diagnostic
      assessments by geriatrically-trained psychiatrists and psychologists, and factor
      analysis. Using a three-part division of "normal," "clinically significant
      depressive symptoms," and "probable major depression," its sensitivity is .80 and
      its specificity is .87 for major depression, and .92 and .87, respectively, for
      any depressive disorder. Separate scoring of affective symptoms versus other
      symptoms of depression (i.e., physiologic, cognitive, or behavioral) can be
      useful for diagnostic and research purposes.

PMID- 7576039
TI  - Efficacy of risperidone for behavioral disorders in the elderly: a clinical
      observation.
AB  - Standard antipsychotics are ineffective in some geriatric patients. In addition,
      they are not helpful for apathy and withdrawal. Studies have demonstrated that
      5HT2 antagonists improve affective symptoms and anxiety; therefore, the efficacy
      of risperidone on agitation and withdrawal was considered. The literature on
      risperidone was reviewed, and the efficacy and limitations of risperidone
      observed in two geriatric patients, one with agitation and another with apathy
      and withdrawal. Risperidone proved to be effective in controlling disruptive
      behavior in geriatric patients. Combined antagonism of D2 and 5HT2 receptors
      might be effective in improving agitation and withdrawal. Risperidone, with both
      D2 and 5HT2 antagonistic properties, seems to have potential as an alternative
      agent in controlling agitation and withdrawal in geriatric patients. Caution and
      need for further observation is recommended.

PMID- 7576041
TI  - Safety and efficacy of caffeine-augmented ECT in elderly depressives: a
      retrospective study.
AB  - Prior studies have shown that in younger depressives undergoing ECT whose seizure
      durations declined despite maximum settings on three different ECT devices,
      pretreatment with caffeine lengthened seizures and resulted in clinical
      improvement. Caffeine (half life, 140-270 minutes) was well tolerated even in
      patients with pre-existing cardiovascular disease. The purpose of this
      retrospective study was to determine the safety and efficacy of caffeine
      augmented ECT in elderly depressed patients. The charts of 14 elderly depressives
      (average age 75.6, range 59-83; 2 males, 12 females) who received caffeine
      augmented ECT were reviewed. Patients pre- and post-ECT medications, blood
      pressure, pulse, and seizure times (cuff and EEG) for each ECT performed were
      noted. The following conclusions were drawn from our study: (1) Caffeine
      definitely increases the seizure length and was useful in our setting when the
      energy settings could not be increased anymore. (2) Caffeine augmentation
      inconsistently causes an increase in pulse rate, on average, in the elderly. (3)
      Caffeine inconsistently produces an increase in mean arterial pressure. (4)
      Caffeine did not consistently produce an increase in the maximum rate-pressure
      product. We conclude from this study that caffeine-augmented ECT is safe and
      effective in increasing seizure duration in the elderly. However, more research
      needs to be done to determine optimal dosing and tolerability.

PMID- 7576043
TI  - Mental status testing in the elderly nursing home population.
AB  - The clinical utility of selected brief cognitive screening instruments in
      detecting dementia in an elderly nursing home population was examined. One
      hundred twenty nursing home residents (mean age 87.9) were administered the Mini
      Mental State Exam (MMSE) and the Modified Mini-Mental State Exam (3MS). The
      majority of the subjects (75%) were also administered the Dementia Rating Scale
      (DRS). Both clinically diagnosed demented (n = 57) and non-demented (n = 63)
      subjects participated in the study. Dementia was diagnosed in accordance with DSM
      III-R criteria by physicians specializing in geriatric medicine. Using standard
      cutoffs for impairment, the 3MS, MMSE, and DRS achieved high sensitivity (82% to
      100%) but low specificity (33% to 52%) in the detection of dementia among nursing
      home residents. Positive predictive values ranged from 52% to 61%, and negative
      predictive values from 77% to 100%. Higher age, lower education, and history of
      depression were significantly associated with misclassification of non-demented
      elderly subjects. Receiver Operating Characteristic (ROC) curve analyses revealed
      optimal classification of dementia with cutoff values of 74 for the 3MS, 22 for
      the MMSE, and 110 for the DRS. The results suggest that the 3MS, MMSE, and DRS do
      not differ significantly with respect to classification accuracy of dementia in a
      nursing home population. Elderly individuals of advanced age (i.e., the oldest
      old) with lower education and a history of depression appear at particular risk
      for dementia misclassification with these instruments. Revised cutoff values for
      impairment should be employed when these instruments are applied to elderly
      residents of nursing homes and the oldest-old.

PMID- 7576042
TI  - Comparison of TCAs and SSRIs in the treatment of major depression in hospitalized
      geriatric patients.
AB  - This study compares a cohort of hospitalized geriatric patients with major
      depression, treated with tricyclic anti-depressants (TCAs), with a cohort of
      patients treated with selective serotonin reuptake inhibitors (SSRIs). The groups
      were compared on demographic, treatment, and outcome variables. Demographically,
      the groups were similar and did not differ on measures of outcome or risk for
      side effects. We conclude that SSRIs are equal to TCAs in the treatment of major
      depression in hospitalized geriatric patients.

PMID- 7576044
TI  - Differentiation of the dementias of Alzheimer's and Parkinson's disease with the
      dementia rating scale.
AB  - The Mattis Dementia Rating Scale (DRS) was used to distinguish between 50
      dementia of the Alzheimer's type (DAT) and 50 Parkinson's disease (PD) subjects
      matched for age, education, and DRS total score. Despite a similar level of
      overall cognitive impairment, the DAT group earned significantly lower scores
      than did the PD group on the Memory subscale, while the PD group displayed lower
      scores than did the DAT subjects on the Construction subscale. Ajackknifed,
      stepwise, linear discriminant function using the five DRS subscales revealed that
      the Memory, Construction, and Initiation subtests significantly distinguished the
      groups. These results suggest qualitative differences in the dementias of DAT and
      PD patients and reveal that such differences can emerge on brief mental status
      examinations.

PMID- 7576045
TI  - Neuropsychiatric manifestations of diffuse Lewy body disease.
AB  - This article reviews the nature and prevalence of Lewy bodies (LBs) found during
      postmortem examination of demented individuals. Neuropathologic findings
      associated with diffuse Lewy body disease (DLBD) are contrasted with those of
      other causes of dementia (e.g., Pick's disease and Alzheimer's disease). A
      sufficiently specific clinical syndrome is suggested to enhance the antemortem
      diagnosis of DLBD. Current and speculative clinical management strategies of DLBD
      are discussed.

PMID- 7576046
TI  - The silicone controversy: towards a resolution.

PMID- 7576048
TI  - What is the MHC?

PMID- 7576047
TI  - BTKbase: a database of XLA-causing mutations. International Study Group.

PMID- 7576049
TI  - Murine CD38: an immunoregulatory ectoenzyme.
AB  - CD38 is an ectoenzyme that utilizes NAD+ and is expressed by many cells of
      hematopoietic origin. Antibodies to CD38 potentiate many biological activities on
      lymphocytes, including induction of murine B-cell proliferation. In this article,
      Frances Lund and colleagues summarize information concerning the expression,
      enzymatic activity and signal transduction pathway utilized by murine CD38.

PMID- 7576050
TI  - Cytokine receptors encoded by poxviruses: a lesson in cytokine biology.
AB  - Poxviruses encode soluble versions of cytokine receptors, which are secreted from
      the infected cell to block the activity of the cognate cytokine. These viruses
      offer a unique model system to study the contribution of cytokines to the host
      response against infection. As discussed here by Antonio Alcami and Geoffrey
      Smith, characterization of poxvirus proteins that counteract the immune response
      may lead to the identification of novel cytokines or cytokine receptors, as well
      as novel strategies to modulate the inflammatory response.

PMID- 7576052
TI  - Serum gangliosides as endogenous immunomodulators.
AB  - Gangliosides suppress various immune activities in vitro and in vivo. Their level
      is significantly elevated in tumors and atherosclerotic aorta tissue, as well as
      in the sera of patients with tumors or atherosclerosis. Here, Lev Bergelson
      suggests that ganglioside-induced immunomodulation might be involved in
      atherogenesis and carcinogenesis, and describes a hypothesis that cites
      gangliosides as a factor interfering with the clearance of low-density
      lipoproteins (LDLs) and promoting the formation of atherosclerotic plaques.

PMID- 7576051
TI  - Ins and outs of LFA-1.
AB  - Leukocyte function-associated molecule 1 (LFA-1) is an integrin that plays a
      major role in the immune system. Recent findings demonstrate that LFA-1 has a two
      way signaling function, mediating cell adhesion and stimulating intracellular
      processes at the same time. Here, Marijke Lub, Yvette van Kooyk and Carl Figdor
      discuss the 'inside-out' and 'outside-in' signaling properties of LFA-1, as a
      prototype leukocyte integrin, in normal and malignant T cells. They integrate
      data into a model that highlights the role of the cytoskeleton in the regulation
      of LFA-1.

PMID- 7576053
TI  - Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional
      significance and clinical relevance.
AB  - Malignant transformation of melanocytes may be associated with changes in the
      expression of major histocompatibility complex (MHC) HLA class I antigens.
      Interest in the characterization of abnormalities in the expression of MHC class
      I by melanoma cells has been rekindled by the current emphasis on the application
      of T-cell-based immunotherapy to melanoma. Here, Soldano Ferrone and Francesco
      Marincola review defects in class I expression as described in melanoma cells, as
      well as the molecular mechanisms, functional significance and clinical
      implications of such defects.

PMID- 7576054
TI  - Linkage of cell-mediated immunity to iron metabolism.
AB  - Iron is essential for growing microorganisms and tumour cells, and is also
      crucial for the proliferation of immune cells. In this review, Gunter Weiss,
      Helmut Wachter and Dietmar Fuchs focus on the complex network of interactions
      that link iron metabolism with cellular immune effector functions involving
      cytokines and nitric oxide, and draw a suitable model for the pathogenesis of
      anaemia of chronic disease.

PMID- 7576055
TI  - The IL-12 p40 homodimer as a specific antagonist of the IL-12 heterodimer.

PMID- 7576056
TI  - Cellular immune responses of macaques exposed to low doses of SIV.

PMID- 7576058
TI  - Special issue: The 9th International Congress of Immunology. San Francisco,
      California, 23-29 July 1995.

PMID- 7576057
TI  - Birth-control vaccines.

PMID- 7576059
TI  - T-cell activation: integration of signals from the antigen receptor and
      costimulatory molecules.

PMID- 7576060
TI  - The B-cell antigen receptor complex and co-receptors.

PMID- 7576062
TI  - Issues concerning the nature of antigen recognition by alpha beta and gamma delta
      T-cell receptors.

PMID- 7576061
TI  - Primary immunodeficiencies: a flurry of new genes.

PMID- 7576063
TI  - Immune-neuroendocrine interactions.

PMID- 7576064
TI  - Advances in intestinal T-cell development and function.

PMID- 7576065
TI  - The germinal center reaction.

PMID- 7576066
TI  - Structure and function of adhesion receptors in leukocyte trafficking.

PMID- 7576067
TI  - Dendritic cells: a major story unfolds.

PMID- 7576068
TI  - From defined human tumor antigens to effective immunization?

PMID- 7576069
TI  - Thymocyte-stromal-cell interactions and T-cell selection.
AB  - Several key advances have been made since 1992, notably in teh area of signalling
      in early T-cell development and in the regulation of T-cell selection. Future
      goals include a fuller understanding of the roles of stromal cells and matrix
      molecules in T-cell development and further elucidation of the diverse signalling
      pathways involved. The ultimate challenge will be to generate T cells from stem
      cells under conditions where all of the developmental cues that earmark
      thymopoiesis are defined.

PMID- 7576070
TI  - Immunity to intracellular microbial pathogens.

PMID- 7576071
TI  - Unlocking the secrets of CTL and NK cells.

PMID- 7576072
TI  - Exponential growth in apoptosis.

PMID- 7576073
TI  - MHC class I-like, class II-like and CD1 molecules: distinct roles in immunity.
AB  - Genes encoding MHC class I-like, class II-like and CD1 molecules have evolved to
      assume specific immunological functions. Some class I-like molecules, including H
      2M3 and Qa-2, present formylated bacterial peptides or have distinct peptide
      binding motifs. The class II-like DMA and DMB gene products play a role in
      presentation of peptide antigen by class II molecules. By contrast, CD1 molecules
      appear to have evolved separately into presenters of nonprotein antigens and into
      TCR ligands with specialized roles in the immune response. Thus, class I-like,
      class II-like and CD1 molecules appear either to serve important independent
      functions or to complement MHC class I and class II. It is expected that future
      efforts will increasingly reveal the functional ramifications of these molecules.

PMID- 7576074
TI  - Organ-specific autoimmunity.

PMID- 7576077
TI  - INTERASMA 95. Poznan, Poland, 30 August-2 September 1995. Abstracts.

PMID- 7576076
TI  - Synthesis and assembly of MHC-peptide complexes.

PMID- 7576075
TI  - The immune response to HIV: potential for immunotherapy?

PMID- 7576079
TI  - 15N resonance assignments of oxidized and reduced Chromatium vinosum high
      potential iron protein.
AB  - The 15N resonances in reduced and oxidized Chromatium vinosum high-potential iron
      protein have been assigned by use of 1H-1H COSY spectra and 1H-15N HMQC. HMQC
      COSY, and HMQC-NOESY spectra. Unambiguous assignment of 70 of 85 backbone 15N
      resonances in the reduced protein and 62 of 85 resonances in the oxidized protein
      are made, as are 12 of 21 side-chain 15N resonances.

PMID- 7576078
TI  - Critical amino acids responsible for conferring calcium channel characteristics
      are located on the surface and around beta-turn potentials of channel proteins.
AB  - Calcium ion is thought to be one of the initial signals in the process of
      synaptic modification. Various reports have described that the critical amino
      acids responsible for determining calcium permeability of ion channels are
      glutamic acid, glutamine, arginine, and asparagine. By using a computational
      method (MacPROT) distinguishing transmembrane, globular, and surface sequences of
      proteins, the present work predicts that the critical amino acids exist within
      surface regions of the proteins. Furthermore, occurrence of beta-turn
      probabilities can be predicted around these critical residues by the protein
      conformational prediction method of Chou and Fasman. The results suggest that the
      critical amino acids exist at hydrophilic spaces or canals of membranous channel
      proteins and that the redirection potential of the protein chain induced by the
      turn structures provides the conformational change requisite for the ion
      selectivity and gating (opening/closing) of the channels.

PMID- 7576080
TI  - Position of the sulfhydryl group and the disulfide bonds of human
      glucocerebrosidase.
AB  - Purified human glucocerebrosidase isolated from placenta was modified with [14C]
      iodoacetic acid without reduction and digested with both protease-V8 at pH 4.0
      followed by alpha-chymotrypsin at pH 7.5. The majority of radioactivity was found
      in a peptide that contained the [14C]-carboxymethylated-cysteine identified as CM
      Cys18. Direct sequencing of the N-terminus of the intact labeled protein
      confirmed the modification of Cys18. For identification of disulfide bond
      containing peptides, another portion of glucocerebrosidase was alkylated with
      nonlabeled iodoacetic acid and then digested with protease V8 and alpha
      chymotrypsin as before. Twenty-eight HPLC fragments were collected. These
      purified peaks were then reduced with beta-mercaptoethanol followed by S
      carboxymethylation with [14C]-iodoacetic acid. Three peptides among these 28
      peptides generated two radioactive daughter peptides. These peptides were
      sequenced and the position of the radioactive CM-cysteines identified. The
      locations of these disulfides are Cys4-Cys16, Cys23-Cys342, and Cys126-Cys248.
      Attempts to reproduce the free sulfhydryl labeling experiments using the
      glucocerebrosidase isolated from Ceredase proved unsuccessful. No label was
      incorporated by this enzyme prior to reduction. This result suggests that the
      form of the protein used in the clinic differs from the native protein.

PMID- 7576082
TI  - Phosphorylation of beta-lactoglobulin using amino acids as the sole base and
      nucleophile of the reaction.
AB  - beta-Lactoglobulin was phosphorylated with 20, 40, and 80 mol of POCl3/mol
      protein in the presence of 4, 5, and 6 molar excess of basic amino acid per mol
      POCl3. Maximal phosphorylation yields of 5 and 3 mol P/mol protein were achieved
      when the highest stoichiometries of POCl3/arginine and lysine were used.
      Proportional high amounts of basic amino acids were also grafted to the protein
      molecule during its phosphorylation through the phosphoamide bond. Modified
      proteins displayed increased negative charges and reduced isoelectric points and
      were monomeric. The phosphorylated and phosphoamidated beta-lactoglobulin showed
      improved functional properties.

PMID- 7576081
TI  - Identification of a stable complex of trichosanthin with nicotinamide adenine
      dinucleotide phosphate.
AB  - Trichosanthin, a type I ribosome-inactivating protein with RNA N-glycosidase
      activity, forms a stable complex with nicotinamide adenine dinucleotide
      phosphate, a substrate analog. Difference UV spectroscopy, fluorescence
      spectroscopy, and 31P NMR are used to identify the formation of the complex,
      followed by a crystal structure analysis carried out to elucidate the active-site
      structure of trichosanthin. The determination of germinal vesicle breakdown
      indicates that the complex does not, at least for abortion-inducing activity,
      result in competitive inhibition to the protein.

PMID- 7576084
TI  - Epitope identification by polyclonal antibody from phage-displayed random peptide
      library.
AB  - Screening of bioactive peptides from random peptide libraries using monoclonal
      antibodies as ligates is an effective method to define epitopes of protein
      antigens. However, it is thought that polyclonal antibodies might also serve as
      promising ligates for screening. We illustrate this approach by using recombinant
      human lymphotoxin (rhLT) polyclonal antibody as a model. The procedure consists
      in (a) affinity purification of polyclonal antibody to obtain the "monospecific"
      antibody, (b) screening against a phage-displayed random peptide library using
      the affinity-purified antibody, (c) plating the enriched phage on agar plates,
      randomly picking clones, and selecting the positive ones by dot blotting, (d) DNA
      sequencing of the positive clones and conducting a homology search against the
      protein sequence databank, and (e) confirming the epitopes by chemical peptide
      synthesis. By employing this procedure, we identified a dominant epitope RQHPKM,
      located at residues 15-20 of the human lymphotoxin amino acid sequence. The
      usefulness of this general procedure is discussed.

PMID- 7576086
TI  - Glutathione adducts, not carbamylated lysines, are the major modification of lens
      alpha-crystallins from renal failure patients.
AB  - alpha-Crystallins from the water-soluble and the water-insoluble, guanidine
      soluble portions of lenses from four renal failure patients and two normal donors
      of similar age were isolated and enzymatically digested into peptides. Molecular
      weights of the peptides, determined by fast atom bombardment mass spectrometry,
      indicated modifications specifically associated with renal failure. The only
      modifications observed in the alpha-crystallins from renal failure patients, but
      not in the normal old lenses, were glutathione adducts to Cys 131 and Cys 142.
      These adducts were present in the lenses of all four renal failure patients, but
      not in the two normal old lenses. The four lenses from the renal failure patients
      were searched for evidence of carbamylation at lysyl or cysteinyl residues:
      carbamylation was not detected. Because the same mass spectrometric methods had
      previously demonstrated sufficient sensitivity and specificity to detect as
      little as 5% modification in the examination of in vitro carbamylated bovine
      lenses, these results indicated that carbamylation is not a major modification of
      the lens alpha-crystallins of renal failure patients.

PMID- 7576087
TI  - Output factors for irregularly shaped electron fields.
AB  - It is necessary to know the output factors (dose per monitor unit at depth of
      maximum) for irregularly shaped electron beam fields to accurately deliver the
      prescribed dose to the target. Measuring the output factors for individually
      shaped electron beam fields for each patient is inconvenient. Using the measured
      output factors for two square fields, one can obtain the output factor for an
      irregular shaped electron portal with area intermediate between the areas of the
      two square fields, by obtaining the equivalent square area (as with photons) of
      the irregularly shaped field, and then interpolating between the output factors
      of the two square field areas to obtain the output factor for the irregularly
      shaped field. This empirical method offers a simple, practical solution. The
      accuracy of the method is about 1% to 2%, depending on the shape and size of the
      irregularly shaped electron field.

PMID- 7576083
TI  - Histone-poly(A) hybrid molecules as tools to block nuclear pores.
AB  - Histone-poly(A) hybrid molecules were used for transport experiments with
      resealed nuclear envelopes and after attachment of a cleavable cross-linker
      (SASD) to identify nuclear proteins. In contrast to histones, the hybrid
      molecules cannot be accumulated in resealed nuclear envelopes, and in contrast to
      poly(A), the export of hybrids from preloaded nuclear envelopes is completely
      impaired. The experiments strongly confirm the existence of poly(A) as an export
      signal in mRNA which counteracts the nuclear location signals (NLS) in histones.
      The contradicting transport signals in the hybrid molecules impair translocation
      through the nuclear pore complex. The failure to accumulate hybrid molecules into
      resealed nuclear envelopes results from the covalent attachment of polyadenylic
      acid to histones in a strict 1:1 molar ratio. This was demonstrated in control
      transport experiments where radiolabeled histones were simply mixed with
      nonlabeled poly(A) or radiolabeled poly(A) mixed with nonlabeled histones. In
      comparison, control uptake experiments with histones covalently linked to a
      single UMP-mononucleotide are strongly enhanced. Such controls exclude the
      conceivable possibility of a simple masking of the nuclear location signal in the
      histones by the covalent attached poly(A) moiety. Photoreactive histone-poly(A)
      hybrid analogs serve to identify nuclear envelope proteins--presumably in the
      nuclear pore--with molecular weights of 110, 80, and 71.4 kDa.

PMID- 7576085
TI  - Solution properties of Escherichia coli-expressed VH domain of anti-neuraminidase
      antibody NC41.
AB  - The VH domain of anti-influenza neuraminidase antibody NC41, with and without a C
      terminal hydrophilic marker peptide (FLAG), has been expressed in high yield (15
      27 mg/L) in Escherichia coli. Both forms were secreted into the periplasm where
      they formed insoluble aggregates which were solubilized quantitatively with 2 M
      guanidine hydrochloride and purified to homogeneity by ion-exchange
      chromatography. The VH-FLAG was composed of three isoforms (pI values of
      approximately 4.6, 4.9, and 5.3) and the VH molecule was composed of two isoforms
      with pI values of 5.1 and 6.7; the difference between the VH isoforms was shown
      to be due to cyclization of the N-terminal glutamine residue in the pI 5.1
      isoform. At 20 degrees C and concentrations of 5-10 mg/ml the VH domain dimerized
      in solution and then partly precipitated, resulting in the broadening of
      resonances in its 1H NMR spectrum. Reagents such as CHAPS, n-ocytylglucoside, and
      ethylene glycol, which presumably mask the exposed hydrophobic interface of the
      VH molecule, prevented dimerization of the VH and permitted good-quality NMR
      spectra on isotope-labeled protein to be obtained.

PMID- 7576089
TI  - A rapid phantom technique for checking blocked vertex fields.
AB  - A simple phantom technique for quality assurance in beam arrangements involving a
      vertex field is described. Clinical personnel can quickly check that blocks for
      the vertex field have been cut to the proper magnification and that the vertex
      field is in proper registration with accompanying isocentric transverse fields.
      Errors can be identified rapidly and corrections made with no inconvenience to
      the patient.

PMID- 7576088
TI  - Verification of surface dose on patients undergoing low to medium energy X-ray
      therapy.
AB  - About 5% of patients still undergo cancer treatment with superficial (peak energy
      < or = 120 kVp) X-ray radiation. Dosimetry of these beams is difficult since the
      maximum dose is delivered at the surface and backscatter contributes
      significantly to the dose. This is particularly a problem in the difficult
      geometries encountered in superficial treatments in the head and neck area. It
      has recently been shown that surface dose measurements in mega-voltage X-ray
      beams can be performed using TLD (Thermoluminescence Dosimetry) extrapolation. In
      this technique, LiF TLD chips with a surface area of 3.15 x 3.15 cm2 and three
      different thicknesses (0.230, 0.099, and 0.038 g/cm2) are used together in the
      same radiation beam which allows the extrapolation of the measured dose back to
      the true surface. The energy response curve of the three thicknesses of LiF chips
      was measured for the energy range of 60kVp, HVL 1.6 mm Al to 300kVp, 4 mm Cu. LiF
      was found to over respond by a factor of 1.7 at 60kVp HVL 1.6 mm Al with respect
      to a 6MV photon beam. A feasibility study was carried out on three patients
      undergoing treatment at 120kVp. Because of the small field sizes involved it was
      necessary to limit irradiation to one or two chips at a time. The dose fall off
      in the first millimetre of tissue could be clearly detected. TLD extrapolation,
      in low to medium energy beams, was found to be useful to assess the dose of
      patients undergoing treatment for superficial lesions.

PMID- 7576090
TI  - Clinical introduction of a commercial treatment chair to facilitate thorax
      irradiation.
AB  - There are occasions when patients can benefit significantly from being treated
      upright. This technique is beneficial in the treatment of Hodgkin's disease when
      the mediastinum is involved. The main benefit is the lung volume spared resulting
      from narrowing of a bulky mediastinum. We purchased a commercial treatment chair
      to facilitate upright treatment. Clinical implementation required rigorous
      testing, documentation of procedures, and acknowledgment of and corresponding
      solutions to limitations. The purchased chair is designed to couple with the
      spine bar of the treatment couch, allowing patient positioning via pendant
      functions. The chair has no obstruction as immobilization is afforded by arm,
      shoulder, and knee supports, which allows isocentric treatments. An additional
      hydraulic mount is used for simulation. We have treated five patients thus far,
      including Hodgkin's disease patients with and without mediastinal involvement,
      and one lung cancer patient with a large lower lobe lesion. All patients have
      benefited by having a greater volume of lung spared (as much as 60% additional
      blocking) when upright simulation films are compared with supine and prone films.
      Immobilization has been adequate as confirmed by daily light field projections
      and portal films. We are routinely evaluating Hodgkin's disease patients for
      upright treatment. Patients treated in the chair have benefited in terms of lung
      volume spared without loss of immobilization. A patient with a large lower lobe
      lung lesion has also benefited as the tumor "dropped," thus affording lung
      sparing via blocking.

PMID- 7576091
TI  - Accuracy of the point source approximation to high dose-rate Ir-192 sources.
AB  - The accuracy of the point source approximation used in dose calculations for an
      implant comprised of multiple high dose rate (HDR) Ir-192 source dwell positions
      is investigated. First, a single dwell position implant is modeled. The exposure
      rate about the source is calculated using both the point source approximation and
      the more rigorous line source formalism. A comparison of these calculated
      exposure rates is made. It is found that for each HDR Ir-192 source dwell
      position, the point source approximation results in a dose overestimation of 1%
      at a distance of 1 cm on the source transverse axis, while dose underestimations
      of more than 2% can be found at a distance of 1 cm on the source longitudinal
      axis. Even larger errors occur closer to the source. The results of this academic
      study are then extended to two clinical cases--an endobronchial treatment and a
      tandem and ovoids setup, both involving multiple source dwell positions. Since
      clinical HDR Ir-192 implants are comprised of many individual source dwell
      positions, there will be inaccuracy in the calculated overall dose distribution
      leading to dose delivery errors. For example, the dose delivered to a
      prescription point located 0.5 cm from an endobronchial applicator will be 3%
      lower than prescribed. Similar errors are produced in gynecologic implants. To
      decrease below 0.5% the dose delivery error resulting from the point source
      approximation, prescription points should be at a distance of at least 1 cm from
      any applicator. Since the dosimetry error is a direct result of the choice of
      model used to describe the source, the use of anisotropy factors accounting for
      the variation of photon fluence around the HDR Ir-192 source will not completely
      correct the calculation.

PMID- 7576092
TI  - A blended beam technique to decrease toxic effects of post mastectomy irradiation
      by combining and sequentially mixing electrons and photons.
AB  - We studied 24 patients with Stage II or Stage III breast carcinoma, post total
      mastectomy, who had received adjuvant loco-regional irradiation (16 patients) or
      were irradiated for chest wall recurrence (8 patients), along with systemic
      chemotherapy and/or hormonotherapy. A technique is described for combining and
      sequentially mixing electron and photon beams. This blended beam method results
      in less severe acute and chronic skin reactions. Dose distribution to the chest
      wall and mediastinum are improved compared to the traditional photon-only
      techniques. At a median followup of four years our expected loco-regional control
      rates are not compromised. This technique is recommended for selected post
      mastectomy patients to reduce toxic effects of chest wall irradiation,
      particularly when chemotherapy lowers skin tolerance and the reserves of the
      heart, lung and bone marrow.

PMID- 7576093
TI  - A comparison of surface doses for two immobilizing systems.
AB  - To achieve accurate and reproducible treatments, many types of immobilizing
      systems have been used. Two of these systems: Alpha Cradle and VacFix, conform
      around the patient to improve day-to-day treatment repositioning. The Alpha
      Cradle system has been in clinical use for several years. The system involves two
      polyurethane chemicals which upon mixing in a latex bag will expand and harden
      around the patient. The second system (VacFix) uses a 0.15 mm thick plastic bag
      loosely filled with 1 mm polysterol spheres. The patient lays on the bag in the
      treatment position and the air is evacuated from the bag. This system retains its
      shape for the entire treatment and can be re-used. In some patient set-ups, it is
      possible that the beam is modified as it passes through these devices, causing a
      potential change in the target dose and an increase in the patient surface dose.
      CT scans of the Alpha Cradle and VacFix systems were performed and relative
      densities were calculated and compared to air. Material densities and surface
      dose data for a Cobalt-60 teletherapy unit and a dual photon linear accelerator
      are presented.

PMID- 7576094
TI  - A new isocenter shift method for ideal geometric matching of two adjacent fields.
AB  - The most commonly used technique for matching two adjoining parallel opposed
      fields has been geometric matching with a skin gap calculation. Many
      modifications have been suggested in order to minimize the shortcomings of this
      technique. Most of these, however, are more complex and time consuming in
      clinical practice, with little dosimetric improvement. We propose a simple new
      method for adjacent field abutment that eliminates hot and cold spots due to
      different beam divergences. This method is based upon the use of a single match
      plane for both the cephalad and caudad parallel opposed beams. The divergence
      angle of these opposed beams is forced to be equal at the junction through the
      use of the same field length and the same target axis distance (TAD). For the
      isocentric treatment case, the procedure is summarized as follows. After setting
      up the cephalad AP/PA fields to midplane in the conventional manner, the patient
      support couch is shifted longitudinally in the cephalad direction by a precise
      distance equal to the cephalad field length. The superior collimator of the
      caudad field is kept the same as for the cephalad field to ensure equal
      divergence angles. The actual irradiated volume of the caudad field is adjusted
      as needed by a large block or an asymmetric jaw. An analogous procedure is
      described for the nonisocentric case. This new isocenter shift method culminates
      in several distinct advantages over the other geometric methods.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576095
TI  - High dose rate (HDR) brachytherapy technique: for carcinoma of uterine cervix
      using Nucletron applicators.
AB  - This study describes our existing treatment method for high dose rate (HDR)
      brachytherapy of carcinoma of uterine cervix using Nucletron applicators. Based
      on our clinical experience with low dose rate (LDR) brachytherapy since 1986, we
      deliver 40-45Gy by external and 30Gy by internal radiation therapy. The change in
      regimen using HDR brachytherapy is that internal radiation dose is given in 5
      fractions at weekly intervals following external radiotherapy. We have analyzed
      the dosimetry of 20 patients; total of 100 treatments done at our center using
      ring-tandem (R-T) and ovoid-tandem (O-T) applicator combinations. Since O-T
      applicator has more flexibility of using desired tandem length and reduced rectum
      and bladder dose due to internal shielding inside the ovoids, we have made the
      transition from R-T to O-T combination of applicator. The dose volume histogram
      of the isodose curve indicates that there is an increase in isodose volume with
      the O-T applicator by as much as 1.5 times as compared to R-T applicator. In
      majority of the treatments, rectum and bladder doses are less than 70% of target
      dose, however in very few treatments, the bladder dose has increased to more than
      the target dose, in which case, the applicators were reseated and added more
      packing or reduced the dose per fraction, for better tolerance of late responding
      normal tissues. All our dose calculations are checked with an independent
      calculation method and agreement was obtained with in 5-7% discrepancy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576096
TI  - A patient dose verification program using diode detectors.
AB  - In this work, we present a comprehensive patient dose verification program using
      a commercial dual diode detector system for external photon beam radiotherapy. To
      achieve acceptable accuracy, factors potentially affecting diode sensitivity need
      to be carefully considered in dose determination. Several authors have shown that
      diode sensitivity depends on temperature, saturation, linearity, radiation
      damage, and beam incidence angle. In addition, we found that the use of wedge
      filters, block trays at a close distance to the detectors, variation in radiation
      field size, as well as measurement SSDs may affect diode sensitivity
      significantly. In practice, we use a 5% dose deviation of measured dose from
      expected patient dose to prompt reevaluation of patient dosimetry. This yields a
      90% acceptance rate in clinical patient cases.

PMID- 7576097
TI  - LAR-PTPase cDNA transfection suppression of tumor growth of neu oncogene
      transformed human breast carcinoma cells.
AB  - The incidence of amplification of neu oncogene-encoded protein tyrosine kinase in
      human breast cancer strongly supports the concept that protein tyrosine
      phosphorylation and dephosphorylation are key regulatory mechanisms in the
      proliferation, differentiation, and neoplastic transformation of breast
      epithelial cells. We examined the potential regulatory role of protein tyrosine
      phosphatases (PTPases) in the maintenance of cellular tyrosine phosphorylation by
      the introduction of leukocyte common-antigen-related PTPase (LAR-PTPase) cDNA
      into a tumorigenic human breast carcinoma cell line that overexpressed p185neu
      protein tyrosine kinase. The transfected human breast carcinoma cells expressed
      elevated levels of LAR-PTPase as assessed by reverse transcription-polymerase
      chain reaction and by analysis of LAR-PTPase protein. The LAR-PTPase-transfected
      human breast carcinoma cells had a significantly (P < 0.01) slower proliferation
      rate in vitro than control-transfected cells. When LAR-PTPase-transfected cells
      were inoculated into athymic nude mice, a consistent and significant (P < 0.05)
      suppression of tumor growth was observed. These results provide evidence that a
      specific PTPase, LAR-PTPase, can play a suppressive regulatory role in the tumor
      growth of human breast carcinoma cells that overexpress p185neu protein tyrosine
      kinase.

PMID- 7576098
TI  - Ultraviolet light-responsive element (TGACAACA)-binding proteins in cells of
      xeroderma pigmentosum patients.
AB  - The ultraviolet light (UV)-responsive element (URE) is an octamer sequence,
      TGACAACA, that shares homology with cyclic AMP-responsive element and activator
      protein 1 target sequences. Because URE-binding proteins have been shown to play
      a role in cellular response to DNA damage, we determined their expression and DNA
      binding activities in repair-deficient cells. Of the complementation groups
      tested, only xeroderma pigmentosum (XP)-C cells induced expression of c-jun after
      UV irradiation; this correlated with XP-C binding to the URE and resembled the
      pattern observed with normal human fibroblasts. In other cases either a decrease
      (XP-A) or no change (XP-D) in URE-binding activities was noticed, which may be
      associated with decreased c-fos and poor c-jun expression after UV irradiation.
      That XP-C cells were the only complementation group exhibiting URE-binding
      activities similar to those of repair-proficient cells points to the possible
      correlation between proper repair of transcriptionally active genes and the
      expression and activities of proteins implicated in the cellular response to UV
      irradiation.

PMID- 7576099
TI  - 12-Lipoxygenase isoenzymes in mouse skin tumor development.
AB  - 12-lipoxygenase-catalyzed arachidonic acid metabolism in normal and neoplastic
      mouse epidermis was assessed by cDNA cloning of the epidermal 12-lipoxygenases
      and by studying their expression patterns, enzyme activities, and product levels.
      Papillomas and squamous cell carcinomas induced by the initiation/promotion
      protocol contained 50- to 60-fold more 12-hydroxy-5,8,10,14-eicosatetraenoic acid
      (HETE) than normal epidermis. The ratio of S to R enantiomers was 9:1. This
      indicates that most of this eicosanoid was of enzymatic origin. Accordingly, cell
      free preparations of the tumors exhibited about fivefold elevated 12-lipoxygenase
      activities. A papilloma-derived cDNA library was screened with human platelet
      type 12-lipoxygenase cDNA probes. Two cDNA clones encoding the platelet-type and
      the leukocyte-type isoforms of murine 12-lipoxygenase were isolated,
      demonstrating the coexpression of the isoenzymes in the same tissue and species.
      When expressed in COS-7 cells, the recombinant enzymes showed the characteristic
      substrate selectivity and product profile, with the leukocyte-type enzyme
      metabolizing linoleic and arachidonic acid to 13-hydroxy-9,11-octadecadienoic
      acid and to 12- and 15-HETE, respectively, and the platelet-type enzyme
      oxygenating exclusively arachidonic acid to 12-HETE. In epidermis in vivo and in
      keratinocytes in culture, only the platelet-type 12-lipoxygenase (mRNA and
      protein) was detectable. In mouse epidermis both isoenzymes were induced
      transiently by phorbol esters. Most tumors showed constitutive overexpression of
      platelet-type mRNA, whereas leukocyte-type specific transcripts were detectable
      only in a few tumors. These data suggest that the platelet-type enzyme is the 12
      lipoxygenase isoform of keratinocytes that is responsible for the generation of
      most of the 12-HETE found in neoplastic epidermis.

PMID- 7576100
TI  - Cytochrome P450 2A of nasal epithelium: regulation and role in carcinogen
      metabolism.
AB  - In this study, we found that rat nasal coumarin-7-hydroxylase (COH) activity was
      two orders of magnitude higher than rat hepatic COH activity and could be induced
      by adding coumarin to the rats' drinking water. In western blot analysis, an anti
      cytochrome P450 (Cyp) 2a-5 (mouse liver COH) antibody recognized a sharp band in
      the microsomal fraction of rat nasal epithelium but not of the liver; the band
      comigrated with Cyp2a-5. The intensity of the band was increased by the coumarin
      treatment. Similarly, in northern blot analysis, a cDNA probe specific for Cyp2a
      5 recognized an mRNA in the nasal epithelium having the same size as mouse liver
      Cyp2a-5 mRNA; however, no hybridizable mRNA was recognized in liver preparations.
      Unlike the protein level, the level of the mRNA was not increased by coumarin.
      When northern blot analyses were performed with two oligoprobes specific for rat
      lung CYP2A3, an mRNA of similar size to Cyp2a-5 mRNA was recognized. In
      immunoinhibition analysis, anti-Cyp2a-5 antibody inhibited rat nasal COH activity
      and aflatoxin B1 (AFB1) metabolism completely. It inhibited N-nitrosodiethylamine
      (NDEA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by 80
      90%. In contrast, the hepatic metabolism of the four compounds was not affected
      by the antibody. When coumarin instead of anti-Cyp2a-5 antibody was used, a
      strong but variable inhibition of the nasal metabolism of AFB1, NDEA, and NNK was
      seen. The results suggest that an enzyme or enzymes similar to mouse liver Cyp2a
      5, one of which may be CYP2A3, is expressed at high levels in rat nasal
      epithelium but not in the liver and that its expression is increased by coumarin,
      an odorant and a substrate of Cyp2a-5. The increase probably occurs by protein
      stabilization or stimulation of translation. The results also show that the
      enzyme has a key role in the nasal metabolism of three well-known carcinogens,
      AFB1, NDEA, and NNK and may therefore be an important contributing factor in
      nasal carcinogenesis.

PMID- 7576101
TI  - Genetic mapping and expression analysis of the murine DNA ligase I gene.
AB  - We mapped the murine DNA ligase I gene (Lig1) in the mouse genome by using a
      mapping panel from an interspecific cross. Lig1 mapped to a centromeric part of
      chromosome 7, a region homologous to human chromosome 19q, where the human
      homologue LIG1 was localized. In addition, Lig1 expression was analyzed during
      the course of mouse liver-cell regeneration induced by partial hepatectomy,
      necrogenic doses of carbon tetrachloride, or the mitogen 1,4-bis[2-(3,5
      dichloropyridyloxy)]benzene. The results demonstrate that Lig1 is expressed in
      the liver during active cell proliferation.

PMID- 7576102
TI  - Delay of dimethylbenz[a]anthracene-induced mammary tumorigenesis in transgenic
      mice by apoptosis induced by an unusual mutant p53 protein.
AB  - Murine p53 containing an Arg-->Leu substitution at amino acid 172 possesses many
      properties characteristic of wild-type p53, including the ability to induce
      p21/WAF/Cip1 and apoptosis. To determine if p53-dependent apoptosis plays a
      critical role in mammary tumorigenesis, transgenic mice were generated in which
      the expression of this mutant p53 protein was targeted to the mammary gland by
      using the rat whey acidic protein gene promoter. Mice bearing pituitary isografts
      were treated with 7,12-dimethylbenz[a]anthracene (DMBA) and examined for mammary
      tumor development. Mice overexpressing the p53 transgene exhibited a
      statistically significant increase in apoptosis in the mammary gland and a
      statistically significant decrease in the incidence of DMBA-induced mammary
      tumors. No difference in tumor incidence was observed in mice without pituitary
      isografts who were treated with DMBA, because the transgene is not overexpressed
      in the absence of hormone stimulation provided by the pituitary isograft. The
      unexpected wild-type properties of the 172Arg-->Leu mutant p53, including its
      ability to stimulate apoptosis, make it a possible candidate for use in gene
      therapy protocols.

PMID- 7576104
TI  - Promoter demethylation in MMTV/N-rasN transgenic mice required for transgene
      expression and tumorigenesis.
AB  - We studied demethylation within the transgene promoter in transgenic mice
      carrying the N-ras proto-oncogene driven by the mouse mammary tumor long terminal
      repeat (MMTV/N-rasN) and the relationship of demethylation to transgene
      overexpression and tumorigenesis. Demethylation at Fspl or Clal sites correlated
      with age of the animal and transgene expression in nontumorous mammary gland.
      Demethylation preceded expression in this tissue. In lymphomas and mammary
      tumors, the promoter Fspl and Clal sites were significantly more demethylated
      than in nontumorous control tissues. The Aval, Cfol, and Hpall sites were also
      found to be undermethylated in older animals and showed differences between tumor
      and control tissues. Two additional sites (Eagl and Narl) remained fully
      methylated in all tissues. In contrast with normal tissue, demethylation at the
      Fspl and Clal sites and expression were not correlated in tumor tissue. An
      increase in expression in normal tissue initially occurred and was correlated
      with the level of promoter demethylation; this increase was followed by a further
      increment in transgene expression when tumors developed. Thus, promoter
      demethylation leading to transgene overexpression was associated with long
      latency tumorigenesis in MMTV/N-rasN transgenic mice. Demethylation of proto
      oncogene promoters may therefore be a mechanism of carcinogenesis that requires
      further investigation in human tumors.

PMID- 7576103
TI  - Frameshift mutation in codon 176 of the p53 gene in rat esophageal epithelial
      cells transformed by benzo[a]pyrene dihydrodiol.
AB  - Mutations in the p53 tumor suppressor gene have been associated with exposure to
      environmental chemical carcinogens. Cultured rat esophageal epithelial cells were
      transformed in vitro by treatment with benzo[a]pyrene dihydrodiol (BP-DHD). A BP
      DHD-transformed cell line and control cell lines were analyzed for mutations in
      the p53 gene and in the Ha-ras gene by single-strand conformation polymorphism
      analysis of polymerase chain reaction-amplified products and direct DNA
      sequencing. The deletion of one cytosine in codons 174-176 (TGCCCCCAC-->TGCCCCAC)
      of the p53 gene was found only in the BP-DHD-transformed cell line. The BP-DHD
      transformed cells were highly invasive and tumorigenic when transplanted into
      syngeneic rats, whereas control lines either were nontumorigenic or formed
      epithelial cysts. BP-DHD-transformed cells and control lines were negative for
      mutations in the Ha-ras gene. Our results suggest that the tumorigenic potential
      of the BP-DHD-transformed cell line is associated with a frameshift mutation in
      codon 176 of the p53 gene but not with mutations in the Ha-ras gene. The G/C-rich
      codons 174-176 in the rat p53 gene may be specific targets for BP-DHD.

PMID- 7576105
TI  - Alterations of multiple tumor suppressor genes (p53 (17p13), p16INK4 (9p21), and
      DBM (13q14)) in B-cell chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) samples were screened for alterations
      in multiple tumor suppressor genes (p53 (17p13), p16INK4 (9p21), and disrupted in
      B-cell malignancy (DBM) (13q14) by using polymerase chain reaction-based assays.
      Eleven percent (11 of 96) of the B-CLL cases analyzed in this study and a
      previous study had mutations in the p53 gene. In contrast, analysis of the p16
      gene showed none of 80 B-CLL cases had mutations and five cases (6%) had
      homozygous deletions. Deletions of 13q14 (DBM) occurred in 18% (17 of 96) of
      patients surveyed. Thus, 28 of 96 cases showed an alteration in one or more of
      the three tumor suppressor loci examined. However, cases with p53 mutations
      rarely showed simultaneous loss of DBM. Our results suggest that inactivation of
      the tumor suppressor genes p53 and DBM may be mutually exclusive, thus providing
      alternate pathways for tumor development in B-CLL patients.

PMID- 7576106
TI  - Homozygous deletions but no sequence mutations in coding regions of p15 or p16 in
      human primary bladder tumors.
AB  - Chromosome 9p21 appears to harbor a tumor suppressor gene, as evidenced by
      deletions in this region in a variety of human primary tumors and cell lines. To
      map the deletion at 9p21 in bladder tumors, we analyzed DNA from 28 tumor and
      normal pairs at five microsatellite markers that flank the region occupied by the
      putative tumor suppressor genes p16 and p15. Loss of heterozygosity (LOH) at the
      markers human interferon (HIFN) alpha and D9S171, which are adjacent to the p15
      and p16 loci, was detected in 41% and 33%, respectively, of informative cases of
      bladder tumors. No sequence mutations were detected in exons 1 or 2 of either p15
      or p16 in any of the bladder tumors. Three sequence-tagged site markers in the
      region bordered by HIFN alpha and D9S171 were used to further map the deleted
      region by multiplex polymerase chain reaction with the HIFN gamma maker (on
      chromosome 12) as a control for amplification. Six of 11 tumors with LOH at
      surrounding markers had homozygous deletions of the marker c5.1, which is located
      within the p16 gene; and two tumors appeared to have homozygous deletions within
      p15 (RN1.1) but not p16 (c5.1). A recently identified microsatellite marker, p16
      CA-1, located 16 kb distal to p16, proved valuable in defining the minimal
      deletion involved in these bladder tumors. Five tumors exhibited homozygous
      deletions of this marker but not HIFN alpha and two tumors showed LOH at this
      marker and homozygous deletion of p16. Although these data could not be used to
      identify p16 or p15 as the definitive tumor suppressor gene in this region that
      is involved in bladder carcinogenesis, they suggest that homozygous deletion is a
      common mechanism of loss of tumor suppressor gene function in this region.

PMID- 7576107
TI  - Expression of c-myc in altered hepatic foci induced in rats by various single
      doses of diethylnitrosamine and promotion by 0.05% phenobarbital.
AB  - Among the proto-oncogenes examined by northern blot analysis, c-myc, c-Ha-ras, c
      fos, and c-raf-1 have been reported to be activated in rat liver cell carcinomas.
      However, there are relatively few reports on protooncogene expression in altered
      hepatic foci (AHF) early during hepatocarcinogenesis in the rat. In this study,
      diethylnitrosamine (DEN) at doses ranging from 10 to 200 mg/kg was used to
      initiate and phenobarbital (0.05%) to promote AHF in rats. AHF were detected by
      the presence of the marker enzymes glutathione s-transferase, placental form (GST
      P); gamma-glutamyltranspeptidase (GGT); glucose-6-phosphatase (G6Pase); and
      canalicular adenosine triphosphatase (ATPase). Proto-oncogene expression in
      individual AHF was investigated by in situ hybridization (ISH). ISH for the mRNAs
      of c-Ha-ras, c-fos, and c-raf-1 revealed little or no expression in AHF. However,
      the levels of c-myc mRNA were increased in about 10% of the AHF initiated by the
      highest dose of DEN (200 mg/kg). Thus, altered expression of proto-oncogenes was
      not seen in AHF initiated by nonnecrogenic doses of DEN and promoted by
      phenobarbital. However, at the necrogenic dose of 200 mg/kg DEN, c-myc expression
      was found mostly in AHF in which abnormal expression of GST-P, GGT, G6Pase, and
      ATPase was also present, indicating that c-myc expression is correlated with
      phenotypically greater complexity of the AHF, a characteristic of malignant
      hepatic neoplasms in the rat.

PMID- 7576108
TI  - Activating mutations in human c-Ha-ras-1 protooncogene induced by stereoisomeric
      fjord-region benzo[c]chrysene diol-epoxides.
AB  - The mutagenicity of fjord-region benzo[c]chrysene diol-epoxide (BcCDE)
      stereoisomers((+) anti-BcCDE, (-)anti-BcCDE, (+)syn-BcCDE, and (-)syn-BcCDE) was
      studied in a forward-mutation system. pEC plasmid containing the human c-Ha-ras-1
      proto-oncogene was reacted in vitro with each optically active isomer separately
      and transfected into NIH/3T3 cells. Morphologically transformed foci were cloned,
      and DNA obtained from these foci was tested for the presence of Ha-ras-1 sequence
      by Southern blot analysis. A total of 50 transformed foci (11-14 for each
      diastereomer) were generated. To determine the nature of mutations responsible
      for activating the proto-oncogene, regions of the gene likely to contain the
      activating mutations were amplified by polymerase chain reaction and then
      subjected to hybridization with specific oligonucleotides. Gene mutations in 42
      of 50 transformed foci were characterized by these methods, and most were found
      at codon 61 (27), followed by codons 12 (13) and 13 (two). All mutations observed
      were either G --> T or A --> A --> T transversions. Thirty-six were G --> T
      transversion mutations occurring at codons 61, 12, and 13. The remaining six were
      A --> T transversions at codon 61.BcCDE stereoisomers may specifically attack
      guanine and adenine and result in the mutations observed. Some differences in
      codon preference but not in the types of mutations were found among these
      optically active isomers.

PMID- 7576109
TI  - Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor
      production, and differentiation state of human osteosarcoma cell lines.
AB  - Human osteosarcoma and fibrosarcoma cell lines were investigated for alterations
      in oncogenes, tumor suppressor genes, and growth factors, all of which have been
      implicated in tumor formation. Characterization of oncogenes that are involved in
      osteosarcoma formation, including the c-fos and c-myc oncogenes, indicated that
      all six osteosarcoma cell lines examined had 5- to 20-fold amplification of the c
      myc oncogene, whereas neither of two fibrosarcoma cell lines c-myc amplification.
      Interestingly, only three of six osteosarcoma cell lines displayed altered c-myc
      immediate-early gene function. c-fos was found to be normal, both at the gene and
      functional levels, in all six osteosarcoma and both fibrosarcoma cell lines
      tested. Characterization of two tumor suppressor genes, p53 and RB1, that have
      been implicated in osteosarcoma formation indicated that p53 was altered in five
      of six osteosarcoma cell lines, whereas RB1 was altered in only two or six of
      these cell lines. Neither RB1 nor p53 was found to be altered in the fibrosarcoma
      cell lines tested. An additional transformation marker, autocrine growth-factor
      production, was observed in all six osteosarcoma cell lines and both fibrosarcoma
      cell lines examined. Finally, the differentiation state of the osteosarcoma cell
      lines was investigated via the bone differentiation markers alkaline phosphates
      and osteocalcin. Alkaline phosphatase activity was observed in four of six
      osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined. The
      alkaline phosphatase activity was a result of the expression of the
      bone/liver/kidney alkaline phosphatase isoform. High-level osteocalcin expression
      was observed in one of the osteosarcoma cell lines but not in the two
      fibrosarcoma cell lines examined, although all cell lines demonstrated low-level
      osteocalcin expression. Together, these data demonstrate that relatively
      undifferentiated osteosarcomas commonly display c-myc amplification, p53 and RB1
      mutation, and autocrine growth-factor production, all of which may play a role in
      osteosarcomagenesis.

PMID- 7576110
TI  - The effect of the JE (MCP-1) gene, which encodes monocyte chemoattractant protein
      1, on the growth of HeLa cells and derived somatic-cell hybrids in nude mice.
AB  - To investigate the effect of tumor-associated macrophages on the in vivo growth
      properties of cervical carcinoma cells, tumorigenic human papilloma virus (HPV)
      18-positive HeLa cells were transfected with an expression vector harboring the
      cDNA for the macrophage chemoattractant protein-1 JE (MCP-1). Although the
      endogenous gene is present and not structurally rearranged, its expression seems
      to be negatively affected by a still unknown mechanism. Inoculation of JE (MCP-1)
      negative HeLa cells into nude mice led to rapidly growing tumors, where
      macrophage infiltration into the inner tumor mass was not detectable
      immunohistochemically. The activity that attracted mononuclear cells under both
      in vitro and in vivo condition was reconstituted in HeLa cells after transfection
      with the JE (MCP-1) expression vector. Heterotransplantation of those cells into
      immunocompromised animals resulted in significant growth retardation that was
      accompanied by a strong infiltration of macrophages. On the other hand, in vivo
      selection of nonmalignant hybrids made between wild-type HeLa cells and normal
      human fibroblasts in nude mice resulted in tumorigenic segregants 4 mo after
      inoculation into the animals. Monitoring JE (MCP-1) expression directly within
      those nodules, we found that transcription was either absent or only weakly
      detectable. Recultivation of JE (MCP-1)-positive tissue grafts under in vitro
      conditions revealed that the gene was only marginally inducible by tumor necrosis
      factor-alpha, a cytokine that normally induces a very strong activation of
      transcription in nontumorigenic cells. These findings suggest that functional JE
      (MCP-1) expression and in turn activated macrophages may play a pivotal role in
      controlling the proliferation rate of HPV-positive cells in vivo.

PMID- 7576111
TI  - Hepatocarcinogenesis in BXH recombinant inbred strains of mice: analysis of
      diverse phenotypic effects of the hepatocarcinogen sensitivity loci.
AB  - The hepatocarcinogen sensitivity (Hcs) loci were originally identified as
      determinants of the approximately 50-fold higher susceptibility of male C3H/HeJ
      (C3H) mice to perinatally induced hepatocarcinogenesis relative to male C57BL/6J
      (B6) mice. These two inbred strains also differ in other phenotypes related to
      hepatocarcinogenesis, including their incidences of spontaneous liver tumors and
      the properties of neoplastic hepatic lesions. To test the hypothesis that the Hcs
      loci also influence these phenotypes, we characterized male mice from B6, C3H,
      and nine BXH recombinant inbred (RI) strains for spontaneous liver tumor
      development, the frequency of activating mutations in tumors, and the presence of
      cytoplasmic inclusions in preneoplastic lesions. By comparing these results to
      the relative susceptibilities of the parental and RI strains to N,N
      diethylnitrosamine (DEN)- and N-ethyl-N-nitrosourea- induced hepatocarcinogenesis
      in preweanling male mice, we concluded that the C3H alleles of the Hcs loci also
      positively influence the spontaneous development of liver tumors in male animals.
      While strain-dependent differences in the frequency of Ha-ras-1 activation in DEN
      initiated liver tumors were observed, this phenotype was not correlated with
      susceptibility to liver tumor induction. The formation of eosinophilic
      intracytoplasmic inclusion bodies observed specifically in B6 liver tumors, which
      has been suggested to be associated with the resistance of this strain to
      hepatocarcinogenesis, also segregated independently of the Hcs loci.

PMID- 7576113
TI  - Identification of protein kinase C zeta isozyme in hamster pancreas and
      pancreatic carcinoma cell lines.
AB  - Cellular differentiation and proliferation are dependent upon phosphorylation by
      endogenous protein kinase C (PKC) isozymes in many cell types. Western blotting
      with a C-terminally directed rabbit polyclonal anti-PKC zeta antibody detected a
      doublet of approximately 81 kDa in normal hamster pancreatic tissue and hamster
      pancreatic carcinoma (PC-1) and human pancreatic carcinoma (PANC-1) cells.
      Preabsorption of the antibody with the specific peptide blocked the appearance of
      the 81-kDa band, indicating that the band was specifically recognized by the PKC
      zeta antibody. In contrast, antibodies for PKC alpha, beta, gamma, delta, and
      epsilon failed to show specific immunoreactivity for normal pancreatic tissue or
      PANC-1 or PC-1 cells. Immunocytochemical analysis identified PKC zeta in the
      cytoplasm of ductules and large ducts, to a lesser extent in the islets of the
      hamster pancreas, and in the normal cultured pancreatic duct epithelial cells and
      pancreatic carcinoma (PANC-1 and PC-1) cell lines. Specific reactivity was seen
      by electron microscopy in the ductal cells of the normal pancreatic tissue. In
      normal pancreatic ductal tissue and primary pancreatic ductal hyperplasia and
      carcinoma, the proportional labeling of PKC zeta in nuclei and cytoplasm was
      similar. Our results demonstrating the presence of PKC zeta isozyme in the normal
      pancreas, cultured normal pancreatic duct epithelial cells, and pancreatic
      carcinoma cells or carcinoma tissue suggests a role for this isozyme in the
      normal physiology of the pancreas and perhaps in pancreatic carcinoma.

PMID- 7576112
TI  - Distribution of the DNA adducts of 2-amino-3-methylimidazo[4,5-f] quinoline and 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the supF gene as determined by
      polymerase arrest assay.
AB  - The distribution of the adducts of the cooked meat-derived heterocyclic amines 2
      amino-3-methylimidazo[4,5-f] quinoline (IQ) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhlP) was examined in the supF gene of PSP189 by a
      polymerase-arrest assay using thermal-cycle sequencing. The reactive N-acetoxy
      metabolites of both compounds showed an overwhelming preference for reacting with
      guanine residues in the supF gene of the shuttle vector pSP189. The distribution
      of the IQ and PhlP guanine adducts was not random; instead, patterns of adduct
      hot-spots and cold-spots were observed. There was a striking similarity between
      both compounds in their preferred sites of adduct formation. The finding that IQ
      and PhlP adducted to guanine concurred with previous results showing that the
      target sites for IQ and PhlP mutations in supF were also at guanine. However, the
      adduct hot-spot sites were not predictive of the known sites of mutation hot
      spots. In addition, despite the similarity in adduct hot-spots for IQ and PhlP,
      their reported mutation spectra in the supF gene were different. Factors in
      addition to adduct location therefore appear to play a role in the mutation
      spectra induced by the heterocyclic amines in the supF gene.

PMID- 7576114
TI  - Strand bias of ultraviolet light-induced mutations in a transcriptionally active
      gene in human cells.
AB  - Ultraviolet (UV)-induced repair and mutational spectra were analyzed in an
      inducible marker gene, the metallothionein-l/guamine-xanthine phosphoribosyl
      transferase (gpt) fusion gene, carried by an Epstein-Barr virus-derived shuttle
      vector episomically maintained in human cells. The repair rate of UV photodimers
      from the shuttle-vector molecules was typical of transcriptionally active
      sequences, 70% of the dimers being removed within 8 h after irradiation. The
      spectrum obtained under basal gene transcription was compared with that obtained
      under induced transcription. In both cases, base substitutions at dipyrimidine
      sequences predominated. Multiple mutations and deletions probably due to
      recombinational events induced by UV damage were also observed. Most of the UV
      mutated dipyrimidine sites were located in the transcribed strand and were
      independent of the transcriptional activity of the target gene. In contrast, the
      distribution of mutations throughout the coding region of the gpt gene was
      affected by transcription, with a preferential clustering of mutations occurring
      in the 3' half of the gene after transcription induction. The strand bias
      observed in the UV spectra most likely reflects selection for nonfunctional gpt
      protein.

PMID- 7576115
TI  - Detection of antibodies toward epididymal sperm antigens--an obligatory step in
      evaluation of human immunologic infertility?
AB  - PROBLEM: To test the relative impact of epididymal versus ejaculated sperm in
      immunologic infertility. METHOD: Human antibody binding to epididymal and
      ejaculated spermatozoa was compared by flow cytometry (FCM) since it allows
      quantitative analysis of viable sperm while ignoring nonsperm cells. To select
      sera for FCM, GAT, TAT, and ELISA were applied on 145 sera from fertile men,
      idiopathically infertile and varicocele patients. RESULTS: All GAT/TAT-positive
      infertile patients, a representative group of varicocele patients and the fertile
      control, were assessed by FCM. Higher reactivity toward epididymal sperm revealed
      18/22 sera while only four out of them bound to ejaculated sperm stronger than
      the control. All varicocele sera were positive against epididymal while negative
      against ejaculated spermatozoa. CONCLUSIONS: Epididymal sperm antigens may play a
      predominant role in some cases of immunologic infertility. Such patients might
      not be adequately diagnosed and respectively treated due to the limitations of
      diagnostic procedures applying only ejaculated spermatozoa.

PMID- 7576116
TI  - Early pregnancy factor (EPF) as a marker for detecting subclinical embryonic loss
      in clomiphene citrate-treated women.
AB  - PROBLEM: A discrepancy exists between the apparently normal ovulation and the
      pregnancy rates in women treated with clomiphene citrate (CC). Our previous
      studies have indicated that immuno-suppressive "early pregnancy factor" (EPF) is
      a novel marker to detect subclinical embryonic loss in infertile women. METHOD:
      In the present study EPF was used as a marker to detect subclinical embryonic
      loss in women treated with CC with/without gonadotropins. In some of the women
      treated with CC, conception was assisted by artificial insemination with
      husband's semen (AIH). RESULTS: Our results have indicated that fertilization
      occurred (EPF + ve) in 47.7% (52/109) of women treated with CC with/without
      gonadotropins; 13.46% (7/52) retained the fetus and continued pregnancy till full
      term, whereas 78.9% (41/52) did not retain the fetuses. In the group where after
      stimulation, conception was assisted by AIH, fertilization was observed in 38.24%
      (26/68), retention in 11.54% (3/26) but subclinical embryonic loss was observed
      in 80.8% (21/26) cases. CONCLUSION: Thus, our results have indicated that
      subclinical embryonic loss may account for some of the discrepancy observed
      between the apparently normal ovulation and the pregnancy rates in women treated
      with clomiphene citrate.

PMID- 7576117
TI  - Presence of activated macrophages in a murine model of early embryo loss.
AB  - PROBLEM: Even though our knowledge of the phenomenon at play at the fetoplacental
      interface has greatly advanced during the past years, a complete understanding of
      the reasons why the developing embryo is not rejected by maternal immune effector
      cells remains largely unknown. METHODS: We have used immunohistochemistry with
      the macrophage-specific markers F4/80 and MHC II to study the relationship
      between decidual infiltration and resorption in murine models of embryo loss
      between days 6 and 10 of gestation. RESULTS: Analysis of day 8 CBA/J x DBA/2
      pregnancies has revealed 2 distinct populations of embryos. The majority (69.4%)
      expressed low levels of F4/80+ cells, but a minority (30.6%) expressed much
      higher level of the macrophage marker. In FBA/J x BALB/c, most embryos (91.7%)
      expressed low numbers of F4/80+ cells. As earlier experiments established that
      products of activated macrophages (TNF-alpha and nitric oxide) were implicated in
      embryo loss in this model, the activation status of the F4/80+ macrophages was
      assessed through the cell surface expression of MHC II. Again, a similar
      association was established: 30.6% of the CBA/J x DBA/2 embryos were infiltrated
      by significantly more MHC II+ cells than the control CBA/J x BALB/c mating.
      Finally, when coordinate expression of F4/80, MHC II and CD11b was assessed, it
      was found that an embryo significantly infiltrated by cells bearing one of the 3
      markers was also heavily infiltrated by cells bearing the 2 other markers.
      CONCLUSIONS: This study has shown that the augmented infiltration of the deciduum
      with maternal macrophages is an early event which precedes spontaneous abortion
      of the early embryo.

PMID- 7576118
TI  - Seminal fluid and the expression of MHC class I antigens in the placenta of the
      rat.
AB  - PROBLEM: To determine whether seminal fluid influences the expression of MHC
      class I antigens on the surface of basal trophoblast cells in the placenta of the
      rat. METHODS: Transfer of DA x DA embryos into a WF (allogeneic) or DA
      (syngeneic) recipient made pseudopregnant by hormonal treatment followed by
      mating with a vasectomized male (seminal fluid) or by mechanical stimulation (no
      seminal fluid). Antigen expression was determined by electron microscopic
      immunocytochemistry using the appropriate gold-labeled monoclonal antibodies.
      RESULTS: Seminal fluid did not affect the expression of MHC class I antigens on
      the surface of the basal trophoblast in either allogeneic or syngeneic matings.
      CONCLUSIONS: The suppression of the expression of paternal class I antigens on
      the surface of the basal trophoblast cells in allogeneic pregnancies most likely
      occurs at the genome level shortly after fertilization.

PMID- 7576119
TI  - Embryo-associated immunosuppressor factor is produced at the maternal-fetal
      interface in human pregnancy.
AB  - PROBLEM: To study whether embryo associated immunosuppressor factor (EASF) is
      synthesized at the maternal-fetal interface. METHOD: Anti-EASF monoclonal
      antibody H5D12 was used to identify EASF. Paraffin-embedded sections were
      prepared from placental and fetal tissues and immunohistochemistry was done by
      the avidin-biotin-peroxidase technique. EASF was affinity purified using H5D12
      Sepharose 4B from culture media of placental villi and analyzed for
      immunosuppressive activity (by Concanavalin A-induced lymphocyte proliferation
      assay) and molecular weight identity (by metabolic labeling studies with 35S
      methionine followed by immunoprecipitation and SDS-PAGE). RESULTS:
      Immunohistochemical studies demonstrates intense immunostaining of villous
      syncytiotrophoblast and cytotrophoblast cells of first trimester placental
      tissues. Hoffbauer cells and decidual cells stained positive. The same cells in
      second and third trimester placental tissues stained weakly. However, the
      endothelium and smooth muscle cells of fetal blood vessels, fetal ovarian stroma
      and primordial follicles, kidney epithelium, cerebral neurons, and glial cells
      all stained negative. The affinity-purified EASF from the conditioned media of
      placental villi (less than 12 wk gestational age) was identified as a 37-kDa
      molecule with immunosuppressive activity. Metabolic labeling studies revealed
      that placental villi from early gestational age secretes a major factor of 37-kDa
      and minor factors of 41-kDa and 47-kDa molecular weight. CONCLUSIONS: Monoclonal
      antibody H5D12 identifies a factor that is produced by the pre-implantation
      embryo and also synthesized by decidua and trophoblast cells.

PMID- 7576120
TI  - Qualitative and quantitative analysis of T lymphocytes during normal human
      pregnancy.
AB  - PROBLEM: Human reproduction involves contact between cells which are allogeneic
      to one another, however the fetus not only survives but thrives. METHODS: Aspects
      of T-cell-mediated immunity during normal human pregnancy were studied. PBMNCs of
      pregnant and nonpregnant women were stimulated with PHA and cytomegalovirus
      antigens (CMV). The capacity of stimulated cells to proliferate, to produce IL-2
      and IFN-gamma, to express IL-2 receptor (IL2R1) and the effect of rIL2 on the
      proliferation rate of lymphocytes were examined. FACS was utilized for T-cell
      subset comparisons. RESULTS: The proliferation rate, IL-2, and IFN-gamma
      synthesis were all significantly impaired at suboptimal concentration of PHA
      throughout pregnancy. Exogenous rIL-2 corrected this depression of cell-mediated
      immunity (CMI). At optimal concentration of PHA, proliferation rate and
      production of IFN-gamma and IL-2 were all decreased. Exogenous rIL-2 corrected
      these deficits only in the third trimester. Third trimester pregnant women
      demonstrated a significant depression of proliferation as well as IL-2 and IFN
      gamma production after CMV stimulation, which was partially corrected by
      exogenous rIL-2. FACS analysis suggested that after stimulation by CMV and
      optimal concentration of PHA, T cells were activated and both CD4+ and CD8+
      lymphoblasts expressed normal density of IL-2R1. With suboptimal PHA, the number
      of activated CD4+ and CD4+IL2R1+ cells were diminished and CD4+ and CD8+ T
      lymphoblasts expressed lower number of IL2R1. CONCLUSIONS: CD4 T helper (Th1)
      cell function is down regulated progressively during the three trimesters of
      pregnancy without changes in the quantity of T cell subsets.

PMID- 7576121
TI  - Characteristics of perforin expressing lymphocytes within the first trimester
      decidua of human pregnancy.
AB  - PROBLEM: The number of perforin (P)-positive cells in decidua of pregnancy is
      larger than that observed in any other pathological condition. The aim was to
      investigate the distribution and the phenotype of P+ cells. METHOD: Decidual
      tissue was obtained from the first trimester vaginal termination of pregnancy.
      Tissue distribution of P+ cells was analyzed by immunohistochemistry. The method
      for simultaneous measurement of P and cell surface is presented. RESULTS: There
      is no difference in number and distribution of P+ cells between decidua basalis
      (DB) and decidua parietalis (DP). The percentage of P+ decidual lymphocytes (DL)
      is two times higher than in peripheral blood lymphocytes (PBL) (55% vs. 27%), and
      the prevalent phenotype is CD3- CD4- CD8- CD2+ (95%) CD11c+ (68%) and CD56+
      (82%). CD56bright+ DL are also Pbright+ and this is the largest DL subpopulation
      (42.4% DL). Two different subpopulations of CD8+ DL exist: 1) CD8bright+, which
      are CD3+ CD56- P- and 2) CD8dim+, which are CD3- CD56+ P+. CONCLUSION: P
      expressing DL are prevalently nonclassical NK cells (CD16-) with low cytolytic
      activity but fully equipped with potent cytolytic machinery (Pbright+). There are
      no classical cytotoxic lymphocytes (CTL) (CD3+ CD8+ P+) in the decidua, and all
      CD8+ P+ cells are CD3- CD56+. The number of P+ cells is even higher in DP in the
      vicinity of noninvasive trophoblast, than in DB.

PMID- 7576122
TI  - Lack of magainin-like activity in human cervical tissue.
AB  - PROBLEM: The cervix plays an integral role in innate immunity of the human
      reproductive tract. Magainins are antimicrobial and spermicidal peptides recently
      described in human submandibular glands. We investigated the human cervix for
      magainin-like peptides. METHOD: Histologic sections of frozen and paraffin
      embedded cervical tissue from nine subjects were separately incubated with two
      rabbit, polyclonal, anti-magainin antibodies (CB-2 and CB-7) to investigate for
      magainin-like activity in the human cervix. RESULTS: There was no specific
      staining of cervical columnar cells within the endocervical canal or in the
      endocervical crypts. Magainin-like immunoreactivity in the human submandibular
      gland confirmed previous observations. CONCLUSION: Antigen related to magainin
      like peptides were not discovered in the human cervix.

PMID- 7576123
TI  - Purification and partial characterization of an early pregnancy factor-induced
      suppressor factor (EPF-S1).
AB  - PROBLEM: The immunomodulatory properties of early pregnancy factor (EPF) are
      mediated through induction of at least two lymphokines, designated EPF-S1 and EPF
      S2 (previously estimated M(r) 15,000 and 55,000 respectively). The activity of
      the former is MHC-restricted while the latter is restricted to a locus (or loci)
      outside the MHC. The present study established further criteria by which EPF-S1
      and EPF-S2 might be distinguished from each other and compared with other
      suppressor factors. In addition, techniques have been developed to purify EPF-S1
      to homogeneity. METHOD: Congenic mouse strains were used to map the genetic
      restriction of EPF-S2 in the rosette inhibition test and high performance gel
      permeation chromatography was used to demonstrate that EPF-S1 induces EPF-S2 but
      not vice versa. Further studies then focused on isolation of this first component
      of the cascade, EPF-S1, from immune ascites (from growth in athymic mice of the
      anti-EPF-S1 producing rat-mouse hybridoma R2T gamma, in which EPF-S1 is complexed
      to antibody). Techniques used were acidification followed by application to Sep
      pak C18 cartridges, high performance cation-exchange chromatography and two
      reversed-phased HPLC steps on a C3 column. Purified material was analyzed by SDS
      PAGE and Edman degradation. RESULTS: Approximately 10 micrograms EPF-S1 were
      isolated fom 60 ml ascitic fluid. Homogeneity of the purified material was
      demonstrated by SDS-PAGE, where it ran as a single band of approximate M(r)
      12,000 coincident with biological activity. Attempts at Edman degradation
      indicate that the molecule is N-blocked. CONCLUSION: Definitive primary
      characterization of EPF-S1 must await the preparation and isolation of
      proteolytic fragments of the molecule, but the present studies establish
      conditions which make such structural analysis possible.

PMID- 7576126
TI  - Antigen presentation by class I major histocompatibility complex molecules: a
      context for thinking about HLA-G.

PMID- 7576125
TI  - Identification of the complement regulatory proteins CD46, CD55, and CD59 in
      human fallopian tube, endometrium, and cervical mucosa and secretion.
AB  - PROBLEM: Complement lytic activity has been demonstrated, and a potential for its
      activation is present in human cervical and tubal secretions and in the
      endometrium. This necessitates the presence of regulatory mechanisms for
      protection of the sperm and the implanting allogeneic conceptus in the female
      genital tract. Complement regulatory proteins demonstrated on sperm and in
      seminal fluid have been attributed such a role. It is however likely that
      additional protection is required for a successful conception and implantation to
      take place. This lead us to investigate the distribution of the complement
      regulatory factors in cervical mucus and mucosa, uterine endometrium, and
      fallopian tube. METHOD: Endometrium and cervical mucosa were obtained from
      patients undergoing hysterectomy for benign conditions, and specimens were
      selected from different stages of the menstrual cycle. Fallopian tubes were
      obtained from patients submitted for sterilization, while cervical mucus was
      aspirated from volunteers undergoing gynecological examination.
      Immunohistochemistry was performed on all tissue samples, using monoclonal
      antibodies to membrane cofactor protein (MCP), decay accelerating factor (DAF),
      CD59 and complement receptor 1 (CR1). Western blot analysis was performed on
      cervical mucus under nonreducing conditions. RESULTS: MCP, DAF, and CD59 were
      found to be expressed in human endometrium and fallopian tube. No variation in
      expression was detected throughout the menstrual cycle. CR1 was not expressed.
      Soluble forms of DAF and CD59 were found to be present in cervical mucus.
      CONCLUSION: The complement regulatory proteins MCP, DAF, and CD59 are expressed
      throughout the female genital tract, and may thus play an important role in
      protecting the traversing sperm and implanting blastocyst from complement
      mediated damage.

PMID- 7576124
TI  - Analysis of peripheral blood lymphocyte subsets, NK cells, and delayed type
      hypersensitivity skin test in patients with premature ovarian failure.
AB  - PROBLEM: Premature ovarian failure (POF) probably belongs to the group of
      autoimmune endocrinopathies. Cell-mediated immune parameters were investigated.
      Sex steroids have a profound effect on the immune system. POF patients and
      postmenopausal control women (PM) were tested with or without estrogen
      substitution. METHOD: A novel FACS analysis system (using double labeling
      techniques) was used in 30 patients with POF to enumerate the subjects of
      peripheral blood lymphocytes and NK cells. Eighteen PM women and 30 healthy men
      and women served as controls. We also tested the delayed type hypersensitivity
      skin test (DTH) toward Candida in the POF patient group to be informed on their
      cell-mediated immune function. RESULTS: The numbers of blood lymphocytes, CD3+,
      CD4+ and CD8+T cells, were not abnormal in POF patients. However, HLA-DR+T cells
      were increased in POF patients and in PM women (P < 0.05). These elevated numbers
      were partially reversible by estrogen substitution. The number of CD19+ cells (B
      cells) was elevated, whereas CD3-/CD16+/CD56+ cells (NK cells) were decreased in
      POF patients (P < 0.05), irrespective of estrogen substitution. DTH skin tests
      toward 0.1% Candidin (0.1 ml intradermal injection) were negative in 11 out of 20
      tested POF patients, compared to only 2 out of 10 tested controls (P < 0.05).
      CONCLUSION: POF patients show numerous immune cell abnormalities. These
      abnormalities were only partially due to estrogen deficiency. We hypothesize that
      these abnormalities either lead to ovarian autoimmunity or may have direct
      effects on the ovarian function.

PMID- 7576127
TI  - Evidence for a leukocyte adhesion factor produced by the early embryo.
AB  - PROBLEM: To determine if the embryo may induce adhesive molecules needed for
      implantation. METHOD: Determination of whether platelet rosetting around
      lymphocytes might occur when exposed to sera from pregnant, but not nonpregnant
      patients and from culture fluid from embryos but not oocytes. RESULTS: 90.2% of
      women with positive sera beta human chorionic gonadotropin (beta-hCG) levels
      taken at least 12 days postovulation demonstrated platelet rosette factor (PRF)
      vs only 18.7% when beta-hCG was negative. Using mid-luteal phase sera in women
      receiving hCG injection 1 wk before, 64.7% had positive PRF when serial beta-hCG
      levels were positive as did 100% of samples taken from in vitro fertilization
      (IVF) patients; however, only 15.3% were positive with negative serial hCG
      levels. Culture media from fertilized oocytes and embryos tested positive for
      PRF, but follicular fluid and media from unfertilized oocytes were negative.
      CONCLUSION: The early embryo secretes a factor(s) that gains access to maternal
      serum and promotes increased lymphocyte/platelet adhesiveness.

PMID- 7576128
TI  - Direct production of the Fab fragment derived from the sperm immobilizing
      antibody using polymerase chain reaction and cDNA expression vectors.
AB  - PROBLEM: Sperm immobilizing antibodies cause infertility mainly through
      complement dependent sperm immobilization. To analyze any effect of sperm
      immobilizing antibody on fertilization, we had already established cell lines
      that secrete IgM monoclonal antibody (MAb H6-3C4) and IgG monoclonal antibody
      (MAb EnBCMGS). The latter was a class-switched recombinant IgG antibody that
      shares the same variable region as MAb H6-3C4. The biological effects of the IgG
      antibody were also reported previously to eliminate sperm immobilizing or sperm
      agglutinating activities. However, the method of chemical digestion of IgG had
      some disadvantage to prepare the purified Fab fragment stably and in large
      quantities. This time we report a unique method to obtain the recombinant Fab
      fragments (Fab EnBCMGS) using polymerase chain reaction (PCR) and cDNA expression
      vectors. METHOD: Two kinds of PCR primers were designed to make a truncated heavy
      chain (Fd) gene of MAb EnBCMGS. The amplified Fd gene and light chain gene were
      ligated into cDNA expression vectors and then transfected into mammalian cells.
      RESULTS: Expression of the Fd gene and light chain gene were confirmed by
      Northern blotting. Secretion of the recombinant Fab fragment from mammalian cells
      was also confirmed by Western blotting. The Fab fragment showed biological
      activity as is expected by FACS analysis. CONCLUSION: This method enables the
      stable production of genuine Fab fragments of IgG in mammalian cells without any
      chemical treatment that may be time consuming and affect the quality of the Fab
      fragments.

PMID- 7576129
TI  - Comparative studies on the effects of specific immunoneutralization of endogenous
      FSH or LH on testicular germ cell transformations in the adult bonnet monkey
      (Macaca radiata).
AB  - PROBLEM: It is yet to be determined clearly whether the two hormones FSH and T
      act synergistically in the same cell type--the Sertoli cells--to control overall
      spermatogenesis or influence independently the transformation of specific germ
      cell types during spermatogenesis in the adult mammal. METHOD: Adult male bonnet
      monkeys specifically deprived of either FSH or LH using immunoneutralization
      techniques were monitored for changes in testicular germ cell transformation by
      DNA flow cytometry. RESULTS: FSH deprivation caused a significant reduction ( >
      40%; P < 0.05) in [3H] thymidine incorporation into DNA of proliferating 2C
      (spermatogonial) cells, a marked inhibition ( > 50%) in the transformation of 2C
      to primary spermatocytes (4C) and a concomitant, belated reduction (50%) in the
      formation of round spermatids (1C). In contrast, specific LH/T deprivation led to
      an immediate arrest in the meiotic transformation of 4C to 1C/HC leading to an
      effective and significant block ( < 90%; P < 0.01) in sperm production.
      CONCLUSION: Thus, LH rather than FSH deprivation has a more pronounced and
      immediate effect as the former primarily blocks meiosis (4C --> 1C/HC) which
      controls production of spermatids. These data provide evidence for LH/T and FSH
      regulating spermatogenic process in the adult primate by primarily acting at
      specific germ cell transformation steps.

PMID- 7576130
TI  - Histochemical demonstration of interleukin-2 in decidua cells of patients with
      preeclampsia.
AB  - PROBLEM: The objective of this study was to gain insight into the immunological
      aspects of preeclampsia. METHOD: The presence of interleukin-2 (IL-2) protein in
      the decidua was examined in five preeclamptic patients and seven normal pregnant
      women employing the immunohistochemistry. RESULTS: The decidua cells were
      strongly stained for IL-2 in four out of five preeclamptic patients, while only
      very weak, if any, staining was observed in all the uncomplicated pregnant women.
      CONCLUSIONS: IL-2 was clearly present in decidua cells in the preeclamptic
      setting, suggesting the possible involvement of immune-activation in the
      phathophysiology of preeclampsia.

PMID- 7576131
TI  - A subset of patients with recurrent spontaneous abortion is deficient in
      transforming growth factor beta-2-producing "suppressor cells" in uterine tissue
      near the placental attachment site.
AB  - PROBLEM: To determine if patients with unexplained recurrent miscarriage have a
      deficiency of decidual immunosuppressor cells that produce transforming growth
      factor beta type 2, as has been found in mice with abortion due to rejection
      and/or trophoblast failure. METHODS: Decidual biopsy specimens were taken as near
      to the placental attachment site as possible under ultrasound guidance from first
      trimester legal termination (control) patients with recurrent miscarriage and non
      viable pregnancy, and from patients with sporadic missed abortion. The tissue was
      tested for TGF beta-2+ suppressor cells by in situ hybridization,
      immunohistochemistry, and analysis of supernatants. RESULTS: TGF beta-2-related
      suppressor molecules similar but not identical to those identified in pregnant
      mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent
      miscarriage patients showed a lack of suppressor cells and 59% were subnormal in
      comparison to 20 controls and 5 sporadic miscarriage patients, where 80-85% of
      the patients had detectable suppressor cells. CONCLUSIONS: Suppressor cell
      deficiency is compatible with a role for rejection and/or trophoblast failure in
      some patients with recurrent miscarriage. Presence of suppressor cells in most
      patients with missed abortion (4/5) is compatible with an alternative cause of
      fetal death, similar to findings reported in genetic fetal death mice.

PMID- 7576132
TI  - [Analysis of total saponins in traditional Chinese drug radix Astragali].
AB  - An analysis of the total saponins in 11 original species of Radix Astragali has
      been made. The results will be beneficial for drug control and resources
      utilization.

PMID- 7576133
TI  - [Ecological studies on the growth of Pinellia ternata (Thunb.) Breit].
AB  - The results show that the following ecological requirements must be met for
      Pinellia ternata to grow well: warm climate (appropriately 10-27 degrees C),
      adequate humidity and scattering sunlight. Burning sunlight and high temperature,
      as well as waterlogging are harmful to its growth.

PMID- 7576134
TI  - [A preliminary study on bioactivity of orange and tangerine peel extracts against
      aphis and mites].
AB  - An assay was made on the bioactivity of the extracts of tangerine peel from
      Cinocitrus tangerina, orange peel from Citrus sinensis and mixed tangerine peel
      from Cinocitrus sp. against aphis Semia phis heraclei, Aphis craccivora,
      Uroleucon gobonis and Myzus persicae using residual film or topical method, and
      against mites Tetranychus viennensis and T. trancatus using slide-dip or
      immersion method. Test results show that these extracts have strong bioactivity
      against aphids and mites. The corrected mortality regression equations and LC50
      (or LD50) of these extracts to pests are presented.

PMID- 7576135
TI  - [Determination of puerarin in various kinds of radix Puerariae from different
      places].

PMID- 7576136
TI  - [Investigation on decomposition of principal constituents in calcined shell drugs
      and quality of calcined drugs of large-scale production].
AB  - The decomposition rates of CaCO3 in Concha Arcae calcined at various temperatures
      were determined by CO2 gravimetry, and a simple method was established to judge
      the decomposition of CaCO3 in calcined shell drugs. In addition, the quality of
      shell drugs obtained commercially from six cities was compared.

PMID- 7576137
TI  - [Determination of berberine in Phellodendron chinense Schneid and its processed
      products by TLC (thin layer chromatography) densitometry].
AB  - Berberine from crude and processed Phellodendron chinense was determined by UV
      TLC densitometry. The results indicate that the content of berberine in processed
      products is 11.8% to 98% less than that of the crude drug. The recovery of
      berberine is 98% +/- 1.7% and the Standard relative deviation is 1.7%.

PMID- 7576139
TI  - [Inclusion compounds of jiuxin oil with beta-cyclodextrin].
AB  - The inclusion compounds of Jiuxin Oil with beta-cyclodextrin were prepared. The
      influence of temperature, ratio of host and guest molecules, stirring time on
      inclusion were observed. The quantitative determination was performed by gas
      chromatography. Inclusion compounds of Jiuxin Oil were confirmed by differential
      scanning calorimetry and powder X-ray diffractometry.

PMID- 7576140
TI  - [High performance liquid chromatographic determination of sennoside A in maren
      pills].

PMID- 7576138
TI  - [Amylopsin activator in the decoction of fried malt].
AB  - From the decoction of fried malt (Fructus Hordei Germinatus) a kind of amylopsin
      activator was extracted and distinguished as calcium nitrate (with small amount
      of sodium chloride). The existence of this activator may can be explain properly
      why the decoction is helpful to digestion.

PMID- 7576141
TI  - [Constituents of the petroleum ether and ethyl acetate extract fractions from
      Dracaena cochinensis (Lour.) S.C. Chen].
AB  - Six constituents have been isolated from the petroleum ether and ethyl acetate
      extract fractions of Dracaena cochinensis. Their structures have been identified
      as 1,2,4,5-tetrachloro-3,6- dimethoxy-benzene,docosyl alcohol, octadecyl acetate,
      eicosyl acetate, resveratrol and 4',7-dihydroxy-flavone on the basis of physical,
      chemical and spectral deta. Of these compounds 1,2,4,5-tetrachloro-3,6-dimethoxy
      benzene is a new one.

PMID- 7576142
TI  - [Chemical components of Pleurospermum rivulorum (Diels)].

PMID- 7576143
TI  - [RP-HPLC determination of berberine in cortex Phellodendri].
AB  - A reversed-phase high performance liquid chromatographic mothod was developed for
      the determination of berberine in Cortex Phellodendri using a bonded phase column
      (Zorbax C8) with diazepam as the internal standard. The column temperature was 25
      C. The mobile phase was a mixture of acetonitrile-water (35:65, containing
      30mmol/L H3PO4) with a flow rate of lml/min. Berberine was detected by UV
      absorption at 346nm. The standard curve was linear in the range of 0.14 to 2.0
      micrograms. The recovery was 101.7% and RSD 1.83%.

PMID- 7576144
TI  - [Protective effects of Tribulus terrestris L. polysaccharide on genetic damage].

PMID- 7576145
TI  - [Action of Rhodobrum roserm Limpr on changes of red cell aggregation and yield
      shear stress in dogs with acute experimental coronary occlusion].
AB  - Following acute occlusion of the left anterior descending coronary artery in
      dogs, significant increases were observed in the red cell aggregation index,
      yield-shear stress and red cell electrophoretic time in blood drained from
      ischemic area. When transfusion was performed with Rhodobrum roseum solution from
      the right femoral vein, significant rises of the above-said items were observed.

PMID- 7576146
TI  - [Influence of guizhi decoction on myocardial blood flow in rabbits].
AB  - The present study has shown that Guizhi Decoction can increase the normal
      myocardial blood flow in rabbits. The best result can be achieved in twenty
      minutes after the decoction is given (ig).

PMID- 7576147
TI  - [Progress in the research of plant polysaccharides].

PMID- 7576148
TI  - Synthesis of phytohormones by plant-associated bacteria.
AB  - The plant hormones, auxins and cytokinins, are involved in several stages of
      plant growth and development such as cell elongation, cell division, tissue
      differentiation, and apical dominance. The biosynthesis and the underlying
      mechanism of auxins and cytokinins action are subjects of intense investigation.
      Not only plants but also microorganisms can synthesize auxins and cytokinins. The
      role of phytohormone biosynthesis by microorganisms is not fully elucidated: in
      several cases of pathogenic fungi and bacteria these compounds are involved in
      pathogenesis on plants; auxin and cytokinin production may also be involved in
      root growth stimulation by beneficial bacteria and associative symbiosis. The
      genetic mechanism of auxin biosynthesis and regulation by Pseudomonas,
      Agrobacterium, Rhizobium, Bradyrhizobium, and Azospirillum, are well studied; in
      these bacteria several physiological effects have been correlated to the
      bacterial phytohormones biosynthesis. The pathogenic bacteria Pseudomonas and
      Agrobacterium produce indole-3-acetic acid via the indole-3-acetamide pathway,
      for which the genes are plasmid borne. However, they do possess also the indole-3
      pyruvic acid pathway, which is chromosomally encoded. In addition, they have
      genes that can conjugate free auxins or hydrolyze conjugated forms of auxins and
      cytokinins. In Agrobacterium there are also several genes, located near the auxin
      and cytokinin biosynthetic genes, that are involved in the regulation of auxins
      and cytokinins sensibility of the transformed plant tissue. Symbiotic bacteria
      Rhizobium and Bradyrhizobium synthesize indole-3-acetic acid via indole-3-pyruvic
      acid; also the genetic determinants for the indole-3-acetamide pathway have been
      detected, but their activity has not been demonstrated. In the plant growth
      promoting bacterium Azospirillum, as in Agrobacterium and Pseudomonas, both the
      indole-3-pyruvic acid and the indole-3-acetamide pathways are present, although
      in Azospirillum the indole-3-pyruvic acid pathway is of major significance. In
      addition, biochemical evidence for a tryptophan-independent indole-3-acetic acid
      pathway in Azospirillum has been presented.

PMID- 7576149
TI  - Rifamycins: strain improvement program.
AB  - Rifamycins are primarily produced by Gram-positive bacterium Amycolatopsis
      mediterranei, which belongs to the order Actinomycetales. These antibiotics,
      apart from their application against pathogens of tuberculosis and leprosy, have
      also been found to be effective against several other pathogens including
      Mycobacterium avium and Pneumococcus. Because of the importance of rifamycin, the
      producer strain A. mediterranei has been genetically manipulated since 1957 in
      order to develop a strain that can either produce larger amounts of rifamycin or
      derivatives of rifamycin. In this article, the importance of the producer strain,
      traditional methods (mutations and recombination) of strain improvement, their
      limitations, and the development of a cloning vector and transformation methods
      that have made recombinant DNA techniques accessible for genetic manipulations of
      A mediterranei are discussed.

PMID- 7576150
TI  - Microbiology of fresh and restructured lamb meat: a review.
AB  - Microbiology of meats has been a subject of great concern in food science and
      public health in recent years. Although many articles have been devoted to the
      microbiology of beef, pork, and poultry meats, much less has been written about
      microbiology of lamb meat and even less on restructured lamb meat. This article
      presents data on microbiology and shelf-life of fresh lamb meat; restructured
      meat products, restructured lamb meat products, bacteriology of restructured meat
      products, and important foodborne pathogens such as Salmonella, Escherichia coli
      O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential
      use of sodium and potassium lactates to control foodborne pathogens in meats and
      restructured lamb meat is reviewed This article should be of interest to all meat
      scientists, food scientists, and public health microbiologists who are concerned
      with the safety of meats in general and lamb meat in particular.

PMID- 7576151
TI  - Salmonellae and food safety.
AB  - Salmonella is one of the most important foodborne pathogens around the world. The
      knowledge that very low numbers of Salmonella cells can be infectious emphasizes
      the need for stringent food safety measures Traditional methods for isolating and
      identifying Salmonella in food rely on preenrichment, selective enrichment in
      selective and differential media, biochemical tests, and serological
      confirmation. Recent advances in diagnostic technology have considerably altered
      testing methods for foodborne Salmonella. Many commercial assay systems and kits
      that use newer technologies are available to facilitate the identification of
      Salmonella in foods. These systems include miniaturized biochemical tests, new
      media formulations, automated instrumentation, DNA/RNA probes, antibody-dependent
      assays, and polymerase chain reaction. The technologies used for these systems
      are described, and the various kit formats are compared. Among the limitations of
      detection methods in terms of food safety are timeliness, limits of detection,
      and differentiation of virulent and nonvirulent isolates. Current efforts of
      prevention measures and strategies at different links of the food chain such as
      consumer education and hazard analysis and critical control point (HACCP)
      programs are reviewed, Global approaches to food safety are needed..

PMID- 7576152
TI  - Idiosyncratic liver toxicity of nonsteroidal antiinflammatory drugs: molecular
      mechanisms and pathology.
AB  - This review explores the clinical hepatic pathology associated with the use of
      nonsteroidal antiinflammatory drugs (NSAIDs), possible cellular and molecular
      mechanisms of injury, and future challenges. NSAIDs comprise a group of widely
      used compounds that have been associated with rare adverse reactions in the
      liver, including fulminant hepatitis and cholestasis. These reactions are
      idiosyncratic, mostly independent of the dose administered, and host-dependent.
      The mechanisms responsible for the initiation and perpetuation of NSAID-induced
      hepatotoxicity remain poorly understood and have been largely inferred from
      clinical manifestation. A mounting body of evidence, however, indicates that many
      acidic NSAIDs are metabolized to reactive acyl glucuronides that can form
      covalent adducts with plasma proteins and hepatocellular proteins. In hepatocytes
      cocultured with lymphocytes, these NSAID-altered proteins can become antigenic.
      Thus, long-lived, drug-altered proteins may act as immunogens and produce
      cytotoxic T-cell-mediated or antibody-dependent, cell-mediated toxicity in
      susceptible patients. Alternatively, individual abnormalities in metabolism or
      disposition of some NSAIDs may lead to the formation or accumulation of toxic
      metabolites. Additional work with transgenic animal models is needed to permit
      better understanding of the general and specific risk factors involved in the
      pathogenesis of the idiosyncratic liver injuries related to NSAIDs and other
      drugs.

PMID- 7576153
TI  - Pharmacokinetic modeling approaches for describing the uptake, systemic
      distribution, and disposition of inhaled chemicals.
AB  - A fundamental relationship in toxicology is that an external chemical exposure
      leading to an internal tissue dose can result in an adverse biological response.
      An understanding of these relationships in experimental animals is often used to
      extrapolate and predict the potential risk to humans following exposure to toxic
      chemicals. The exposure-dose-response relationships for volatile compounds
      inhaled by the lungs are complicated by the fact that many toxic effects caused
      by these chemicals have been identified in tissues and organ systems other than
      the lungs. Pharmacokinetic modeling approaches have been devised to quantitate
      the relationships between inhaled concentrations of volatile compounds and the
      resulting critical tissue doses in experimental animals. These animal models have
      also been extrapolated to predict chemical disposition in humans for estimation
      of human health risks. This communication reviews three pharmacokinetic
      descriptions, each representing different levels of complexity, that have been
      used to assess chemical disposition of inhaled, volatile chemicals. The
      mathematical structures, assumptions, data needs, and risk assessment
      capabilities of each modeling approach are described.

PMID- 7576154
TI  - Narcosis due to environmental pollutants in aquatic organisms: residue-based
      toxicity, mechanisms, and membrane burdens.
AB  - The well-known correlation between the hydrophobicity of narcotic chemicals and
      the exposure concentration needed to produce an effect indicates that a lipid
      phase in the aquatic organism is the most likely target. The molar concentration
      in aquatic organisms at death is found to be approximately constant for different
      narcotic chemicals, varying from 2 to 8 mmol/kg organism. Because the proportion
      of lipid is known, the lethal in vivo membrane burden can be calculated to be 40
      to 160 mmol/kg lipid. The exact mechanism underlying narcosis is still unknown.
      However, disturbance by narcotic chemicals in model membrane systems has been
      investigated, attention having been paid to disturbance of phospholipids and
      proteins, and of the interaction between the two groups. Model membrane burdens
      of different chemicals have been shown to be approximately constant for a
      particular effect. Different effects are found at different membrane
      concentrations. In the present review, the toxicity of narcotic chemicals to
      aquatic organisms is discussed, the possible mechanisms underlying narcosis are
      reviewed, and a comparison is made between membrane burdens that are lethal in
      vivo and membrane burdens that cause an effect in in vitro systems.

PMID- 7576156
TI  - Toxicological effects of ethanol on human health.
AB  - Moderate ethanol consumption reduces stress and increases feelings of happiness
      and well-being, and may reduce the risk of coronary heart disease. Heavy
      consumption of alcohol, however, may cause addiction and increases all types of
      injury and trauma. Environmental and genetic factors are involved in
      susceptibility to alcoholism. Ethanol can lead to malnutrition, and can exert a
      direct toxicological effect due to its interference with hepatic metabolism and
      immunological functions. A causal effect has been observed between alcohol and
      various cancers. Cessation of alcohol consumption and balanced nutrition are
      recommended primary nonspecific therapeutic measures for alcoholics. Drug
      therapies for alcoholics suffering from liver injury has resulted in mixed
      results. In end-stage liver disease, liver transplantation may be considered.

PMID- 7576155
TI  - The influence of salinity on the toxicity of various classes of chemicals to
      aquatic biota.
AB  - The objective of this study was to review all available aquatic toxicity
      literature regarding the effects of salinity on the toxicity of various classes
      of inorganic and organic chemicals. Toxicity data for studies in which toxicity
      was assessed at various salinities were organized by chemical classes and trophic
      groups. Seventy percent of the studies were conducted with either crustaceans or
      fish. The other 30% were with mollusks, annelids, zooplankton, bacteria,
      phytoplankton, or fungi. Results from 173 data entries showed that negative
      correlations (toxicity increasing with decreasing salinity) were reported most
      frequently (55%), followed by no correlations (27%) and positive correlations
      (18%). The toxicity of most metals such as cadmium, chromium, copper, mercury,
      nickel, and zinc was reported to increase with decreasing salinity. This finding
      is likely related to the greater bioavailability of the free metal ion (toxic
      form) at lower salinity conditions. There was generally no consistent trend for
      the toxicity of most organic chemicals with salinity. The one exception to this
      was reported with organophosphate insecticides, the toxicity of which appeared to
      increase with increasing salinity. Physiological characteristics of the various
      test species were important in determining the toxicity of the various classes of
      chemicals at a range of salinities. Results from various studies showed that
      euryhaline species were more resistant to toxic conditions at isosmotic
      salinities due to minimization of osmotic stress. Specific examples showed that
      fish were more resistant to toxic chemicals at middle salinities when compared
      with either lower or higher extremes. Life history and ecology of test species
      were important factors to consider when interpreting salinity/contaminant
      interaction data.

PMID- 7576157
TI  - Effect of crossmatching on outcome in organ transplantation.
AB  - The complement-dependent cytotoxicity (CDC) crossmatch and the flow cytometry
      crossmatch (FCXM) are both used prospectively in renal transplantation, and their
      use is under evaluation in other types of major organ transplantation. The FCXM
      is the more sensitive method and better predicts outcome in second and subsequent
      renal allografts. Improved survival has unmasked the detrimental effect of a
      positive crossmatch on outcome in liver transplantation. Because of the urgent
      need of liver transplant candidates, it is unrealistic to defer transplantation
      until a crossmatch-negative donor is found; however, additional therapeutic
      measures may be taken to improve outcome for crossmatch-positive liver
      recipients. Some reports suggest that prospective crossmatching may improve
      outcome for sensitized heart recipients, and, additionally, recent studies have
      demonstrated that HLA compatibility between donor and recipient is an independent
      variable affecting survival after heart transplantation, prompting a reassessment
      of the current practice of transplanting hearts without consideration of the HLA
      match.

PMID- 7576158
TI  - Organic acidurias and related abnormalities.
AB  - Organic acid analysis is a powerful technique in the diagnosis of inborn errors
      of metabolism. Since the development of the technique over twenty-five years ago,
      it has evolved into a sophisticated and powerful method and is an essential tool
      in the diagnosis of the organic acidurias. The chemistry and biochemistry of
      organic acids, as well as sample preparation, instrumentation, and many aspects
      of the more commonly used methods for the analysis of these compounds, are
      reviewed. The biochemical and clinical characteristics of each of the primary
      organic acidurias are described. In addition, the various noninherited causes of
      secondary organic acidurias that lead to the excretion of abnormal organic acids
      are also described, and ways of differentiating primary from secondary causes are
      discussed.

PMID- 7576159
TI  - Clinical and biological aspects of acid phosphatase.
AB  - The identity and genetic origins of the nonspecific orthophosphate monoesterases
      with an acid pH optimum--the acid phosphatases--are now becoming clear. They form
      a family of genetically distinct isoenzymes, many of which show significant
      posttranslational modification. Four true isoenzymes exist. The erythrocytic and
      lysosomal forms show widespread distribution and are expressed in most cells; in
      contrast, the prostatic and macrophagic forms have a more limited expression. The
      erythrocytic and macrophagic forms are distinguished from the others in resisting
      inhibition by dextrorotatory tartrate. The prostatic form has long been used as a
      marker for prostatic cancer and the macrophagic forms have been linked with
      miscellaneous disorders, notably increased osteolysis, Gaucher's disease of
      spleen, and hairy cell leukemia, whereas the normal levels of intravesical
      lysosomal acid phosphatase in I cell disease pointed the way toward the
      mechanisms underlying its intracellular processing.

PMID- 7576160
TI  - Cellular, biological, and physicochemical basis for the hard-to-cook defect in
      legume seeds.
AB  - This review integrates current knowledge on the hard-to-cook (HTC) defect in
      legume seeds, with emphasis on the cellular and biological changes during storage
      and soaking, and the physicochemical changes during heating. Several postulated
      mechanisms, including the pectin-cation-phytate model, cell lignification, pectin
      beta-eliminative degradation, and protein denaturation in relation to starch
      gelatinization, are discussed in the context of current evidence. Subsequently, a
      developmental model of legume hardening is presented. It is held that the HTC
      defect develops during aging and soaking and is exhibited through cooking. During
      the process, there are many events involved. Free radical formation, lipid
      peroxidation, acid formation, membrane deterioration, protein denaturation, and
      leakage are events associated with aging and soaking, whereas pectin
      decomposition and solubilization, protein coagulation, and starch gelatinization
      are events that occur during cooking. Cooked HTC seeds are characterized by
      limited cell separation and restricted starch gelatinization. These defective
      features result from a restriction in pectin decomposition and solubilization as
      well as the protein coagulation that prevails over starch gelatinization during
      heating. This multichannel mechanism points to the direct involvement of two
      amphoteric colloids, cell wall pectin and storage protein, both of which are
      sensitive to pH and/or ion composition. The model also indicates the indirect
      involvement of cell membranes and starch granules. Except for events that occur
      during aging and soaking, it is likely that heat-related textural problems in
      other plant tissues may proceed via a mechanism similar to legume hardening.

PMID- 7576161
TI  - Cyanide detoxification in cassava for food and feed uses.
AB  - Cassava (Manihot esculenta Crantz) is an important tropical root crop providing
      energy to about 500 million people. The presence of the two cyanogenic
      glycosides, linamarin and lotaustralin, in cassava is a major factor limiting its
      use as food or feed. Traditional processing techniques practiced in cassava
      production are known to reduce cyanide in tubers and leaves. Drying is the most
      ubiquitous processing operation in many tropical countries. Sun drying eliminates
      more cyanide than oven drying because of the prolonged contact time between
      linamarase and the glucosides in sun drying. Soaking followed by boiling is
      better than soaking or boiling alone in removing cyanide. Traditional African
      food products such as gari and fufu are made by a series of operations such as
      grating, dewatering, fermenting, and roasting. During the various stages of gari
      manufacture, 80 to 95% cyanide loss occurs. The best processing method for the
      use of cassava leaves as human food is pounding the leaves and cooking the mash
      in water. Fermentation, boiling, and ensiling are efficient techniques for
      removing cyanide from cassava peels.

PMID- 7576162
TI  - Anthocyanins in grapes and grape products.
AB  - The types of anthocyanins occurring in grapes, wines, and juices are described
      and their distribution documented. Recent work on the evaluation of red wine
      color during storage and aging is reviewed. Molecular interactions between
      anthocyanins and some of the other red wine molecules are shown to be associated
      with development of new pigments whose formation explains the subtle color
      changes and stabilization occurring on aging of red wines. A detailed description
      of the recovery of anthocyanins from grape pomace and production of natural red
      colorants is also given.

PMID- 7576163
TI  - Fetal haematological response to intra-uterine infection in preterm prelabour
      amniorrhexis.
AB  - The value of fetal haematological indices in the prediction of intra-uterine
      infection in 91 cases of preterm prelabour amniorrhexis was examined.
      Cordocentesis and amniocentesis were performed for the diagnosis of intra-uterine
      infection. The patients were subsequently divided into three groups, depending on
      the results of fetal blood and amniotic fluid cultures. In group 1 there were 53
      patients with negative fetal blood and amniotic fluid cultures, group 2 consisted
      of 22 patients with negative fetal blood, but positive amniotic fluid cultures,
      and in group 3 there were 16 patients with positive fetal blood cultures. The
      mean leucocyte and neutrophil counts in all three groups were significantly
      higher than normal, and in group 3 the values were significantly higher than in
      group 1. The leucocyte and neutrophil counts were above the 95th centile of the
      normal range in 58% (22 cases) and 66% (25 cases), respectively, of the 38 cases
      with positive fetal blood and/or amniotic fluid cultures and in only 15% (8
      cases) and 13% (7 cases), respectively, of the 53 patients with no infection.
      There were no significant differences between the groups, between the patients
      with amniorrhexis or for normal haemoglobin concentration, platelet count, or
      lymphocyte count. In the majority of the cases with positive fetal blood and/or
      amniotic fluid cultures, there is fetal leucocytosis. Since the results of the
      fetal leucocyte and neutrophil counts are available within a few minutes after
      cordocentesis, it would be reasonable to give antibiotics to all patients with a
      fetal leucocyte count above the 95th centile.

PMID- 7576164
TI  - Impact of abnormal second-trimester maternal serum single, double, and triple
      screening on patient choices about prenatal diagnosis.
AB  - The development of multiple-marker biochemical screening has increased the
      percentage of aneuploidies detected for all age groups and has also increased the
      abnormality/amniocentesis ratio from about 1 in 85 for maternal serum alpha
      fetoprotein alone (single screening) to about 1 in 50 for either maternal serum
      alpha-fetoprotein plus human chorionic gonadotropin (double screening) or
      maternal serum alpha-fetoprotein combined with human chorionic gonadotropin and
      unconjugated estriol (triple screening). We evaluated the decisions to have or
      decline amniocentesis of 985 patients 'at risk' by either single, double, or
      triple screening, as multiple markers were phased in over a 3-year period. The
      patient acceptance of the procedure did not change (approximately 80%) either by
      actual risk or type of biochemical screening. The labeling of 'at risk' status is
      more important than actual numerical risks, and the patient perception of risk
      status must be considered in counseling.

PMID- 7576165
TI  - Maternal assessment in the prediction of intrauterine infection in preterm
      prelabor amniorrhexis.
AB  - The objective of this study was to evaluate maternal temperature, heart rate,
      leukocyte count and C-reactive protein in the prediction of fetal bacteraemia and
      positive amniotic fluid cultures in 75 pregnancies complicated by preterm
      prelabor amniorrhexis. Cordocentesis and amniocentesis were performed and fetal
      blood and amniotic fluid were cultured for aerobic and anaerobic bacteria.
      Amniotic fluid was also cultured for Ureaplasma urealyticum and Mycoplasma
      hominis. Patients were classified into 3 groups: negative fetal blood and
      amniotic fluid cultures (group 1, n = 45); negative fetal blood but positive
      amniotic fluid cultures (group 2, n = 18), and positive fetal blood cultures
      (group 3, n = 12). In the groups with intrauterine infection compared to the non
      infected group, the median maternal temperature, leukocyte count and C-reactive
      protein were significantly higher. In groups 1, 2 and 3 the respective incidences
      of maternal pyrexia were 0, 7 and 16% and raised C-reactive protein 13, 28 and
      33%. In pregnancies complicated by preterm prelabor amniorrhexis, maternal
      temperature, heart rate, leukocyte count and C-reactive protein do not provide
      sensitive prediction of intrauterine infection.

PMID- 7576166
TI  - Fetal serum ferritin and cobalamin in red blood cell isoimmunisation.
AB  - Fetal and maternal serum ferritin and cobalamin concentrations were examined in
      40 red blood cell-isoimmunised pregnancies undergoing cordocentesis at 18-38
      weeks of gestation and the values were compared to those of normal pregnancies.
      In the red blood cell-isoimmunised pregnancies, the fetal serum ferritin
      concentration was increased and the cobalamin concentration was decreased,
      whereas maternal serum ferritin was decreased and cobalamin was not significantly
      different from normals. There was a significant association between the degree of
      fetal anaemia and the increase in fetal serum ferritin concentration, but not
      with fetal serum cobalamin. This study suggests that fetal haemolytic anaemia is
      associated with iron overload and cobalamin deficiency.

PMID- 7576167
TI  - Effect of betamethasone on the fetal heart rate pattern assessed by computerized
      cardiotocography in normal twin pregnancies.
AB  - The effects of corticosteroids, given for enhancement of fetal lung maturation,
      on fetal heart rate (FHR) are controversial and may decrease its variability. FHR
      patterns were analyzed by computerized cardiotocography in 46 fetuses from 23
      normal dichorionic twin pregnancies on days 0, 1 and 4-7 while the mothers
      received four intramuscular injections of 3 mg betamethasone sodium and 3 mg
      betamethasone acetate within 48 h to enhance fetal lung maturation. Compared with
      pretreatment values, FHR showed a decrease in long- and short-term variations;
      other parameters, e.g. the number of fetal movements, remained unchanged.
      However, decreased FHR variation was followed by an increase in the acceleration
      rate after maternal administration of betamethasone. These modifications were
      transient and should not lead to unnecessary anxiety or intervention in otherwise
      normal fetuses.

PMID- 7576168
TI  - Utility of fetal intraperitoneal saline infusion in the prenatal evaluation of
      diaphragmatic hernia.
AB  - The diagnosis of a diaphragmatic hernia at 18 weeks gestation by instillation of
      normal saline into the fetal peritoneal cavity under ultrasound guidance is
      described. The procedure established the diaphragmatic defect with certainty,
      outlined the contents of the hernia within the thorax, and demonstrated the
      degree of secondary lung compression.

PMID- 7576169
TI  - Sonographic prenatal diagnosis of ambiguous genitalia.
AB  - A case report is presented herein of a 33-year-old woman with a history of
      congenital adrenal hyperplasia in 2 prior births. At 30 weeks of gestation, a
      scan of the fetal perineum demonstrated ambiguous genitalia which was confirmed
      at birth. This case demonstrates that when the fetal perineum is well visualized,
      the diagnosis of normal and abnormal genital development can be made
      sonographically. This can assist in perinatal/neonatal management, planning and
      in some cases, can also serve as an additional tool to monitor the success of
      prenatal steroid therapy of fetal congenital adrenal hyperplasia.

PMID- 7576171
TI  - A new method for sampling maternal blood in the placental intervillous space.
AB  - The intervillous space (IVS) is part of the histofunctional unit of the human
      placenta and by being a fetal-maternal exchange interface is an important subject
      of study for the understanding of fetal physiology, especially in nutritional
      investigations. A method developed for the collection of IVS blood has permitted
      to evaluate the fetal-maternal exchanges in an effective manner. Two
      disadvantages of this method, however, are the mixing of IVS blood and fetal
      blood and marked hemolysis. In the present study we introduce and describe some
      modifications of this method using a single stylet for the perforation of the
      chorionic plate which simplifies collection and reduces the chance of mixing and
      hemolysis of the samples obtained.

PMID- 7576170
TI  - Changes in blood flow velocity waveforms following fetal blood sampling.
AB  - The umbilical artery, aorta, and middle cerebral artery pulsatility indices were
      investigated by pulsed Doppler ultrasound in 73 fetuses at 18-37 weeks of
      gestation, before and after fetal blood sampling performed either at the
      placental cord insertion (n = 46) or at the intrahepatic vein (n = 27). At the
      end of the procedure, after randomization, 35 fetuses were infused amounts of
      normal saline equal to the blood volume withdrawn, and 38 fetuses served as
      controls. Following blood sampling, the umbilical artery pulsatility indices
      decreased both in controls (p = 0.004) and in the saline group (p = 0.006). The
      middle cerebral artery velocity waveforms exhibited similar changes only in
      controls (p = 0.01), and no changes in fetal heart rate and aortic pulsatility
      indices were recorded in either group. The changes in blood flow velocity
      waveforms did not correlate with gestational age and the blood volume sampled,
      and were similar whether the site of sampling was the placental cord insertion or
      the intrahepatic vein. In 10 acidemic and/or hypoxemic fetuses, pulsatility
      indices in the umbilical and middle cerebral arteries were not modified by the
      blood sampling procedure. The release of vasoactive substances is most likely the
      cause of diminished vascular resistances following fetal blood sampling.
      Hypoxemic/acidemic fetuses may fail to mount a normal vasodilative response to
      needle puncture.

PMID- 7576172
TI  - A non-human primate model for the in utero chronic catheterization of the
      umbilical vein. A preliminary report.
AB  - Short-term ultrasound-guided fetal umbilical cord catheterization in humans has
      been reported. However, before chronic umbilical vein catheterization is
      attempted in humans the technique must be tested in the non-human primate model.
      If the fetus was to tolerate this procedure, chronic fetal umbilical vein
      catheterization could be used for drug administration, parenteral fetal nutrition
      or to monitor the changes of hematologic parameters during and after open or
      endoscopic fetal surgery. In this study, 4 pregnant baboons were used to test the
      feasibility of ultrasound-guided umbilical vein catheterization. Although the
      umbilical vein was successfully catheterized in all the animals, only 1 fetus
      survived the postoperative period. The 3 immediate fetal deaths were due to a
      fetal intra-amniotic hemorrhage, while the most likely cause of death of the 4th
      animal was infection. In the surviving fetus and mother, blood was sampled once a
      day. Neither fetomaternal hemorrhage nor thrombosis could be documented. We
      conclude that ultrasound-guided transplacental umbilical vein chronic
      catheterization is technically difficult but feasible in the baboon model.
      Further studies in this model are needed to improve the catheterization technique
      and to monitor the extent of time that the catheter may be tolerated within the
      umbilical vein.

PMID- 7576173
TI  - Dandy-Walker malformation in a fetus with pentasomy X (49,XXXXX) prenatally
      diagnosed by fluorescence in situ hybridization technique.
AB  - We present the case of a pentasomy X (49,XXXXX) prenatally diagnosed. The
      fluorescent in situ hybridization technique assisted in making the diagnosis. The
      problems identified in this fetus include a Dandy-Walker malformation,
      hydrocephaly, ventricular septal defect, hypertelorism and polyhydramnios.

PMID- 7576174
TI  - How to deal with a rare entity: the coexistence of a complete mole and a healthy
      egg in a twin pregnancy?
AB  - The association of a normal and a molar egg within a twin pregnancy is extremely
      rare. The key to diagnosis is the fetal karyotype, thus allowing elimination of
      its principal differential diagnosis: partial triploid mole. We report a case
      where the evolution of the pregnancy was complicated by severe toxemia.
      Interruption of pregnancy was then necessary, even though a conservative attitude
      had first been considered. Throughout this case, we discuss the means of
      diagnosis and the clinical handling of this rare entity.

PMID- 7576176
TI  - Cyclin B and Cdc2 expression and Cd2 kinase activity during Dictyostelium
      differentiation.
AB  - Although Dictyostelium differentiation occurs in the absence of external
      nutrients, two periods of mitosis occur, one during early development and one
      during the formation of the migrating pseudoplasmodium. We showed previously that
      cyclin B mRNA levels vary in a cell cycle dependent manner during vegetative cell
      growth. In the present study, we report that cyclin B mRNA levels change
      dramatically during development, reaching a maximum at the tipped aggregate
      stage. However, amounts of cyclin B protein vary only slightly, peaking during
      early development and decreasing during late aggregation and pseudoplasmodial
      formation. Cdc2 protein levels also remain relatively constant during
      development. Cdc2-histone H1 kinase activity was considerably higher in
      vegetative cell extracts of transformants that expressed large amounts of
      truncated cyclin B protein in comparison to extracts of the parental Ax-2 cells.
      These results suggest that Cdc2 kinase activity is dependent upon the level of
      cyclin B in vegetative cells. This result is consistent with the idea that
      variations in the level of cyclin B during growth regulate the cell cycle. When
      Cdc2 histone H1 kinase activity was determined during development, it was also
      found that activity correlated reasonably well with the amount of cyclin B
      protein. Thus, there was an increase in Cdc2 histone H1 kinase activity early in
      development, and then levels decreased as development progressed. The increase in
      Cdc2 histone H1 kinase activity that occurs early in development following
      starvation may be important in accelerating G2-phase cells through into mitosis.
      There was no increase in Cdc2 histone H1 kinase that accompanied the previously
      reported late developmental mitosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576175
TI  - Severe urethral obstruction diagnosed at 14 weeks' gestation: variability of
      outcome with and without drainage.
AB  - We present 3 case reports to illustrate the variability of outcome of severe
      fetal posterior urethral obstruction. Two of the described cases support the view
      that early in-utero decompression of an obstructed fetal urinary system into the
      amniotic cavity, in the selected patient, will allow adequate lung development
      and will prevent the development of severe renal dysplasia. It will not prevent
      the abdominal wall deformity of the prune belly syndrome. The evidence suggests
      that to allow maximum time for lung development and to prevent increasing renal
      dysplasia, drainage should be performed before 18 weeks of gestation. To obtain
      maximum effect, this drainage should continue until at least 32-33 weeks'
      gestation, so that the possible respiratory problems of prematurity would not be
      severe enough to compound the degree of lung hypoplasia which might be present.
      Case 3 supports our view that an endoscopic approach to in-utero drainage of the
      urinary tract has the advantage of achieving drainage with minimal risk to both
      mother and fetus.

PMID- 7576177
TI  - Regulation of H1(0) gene expression by nuclear receptors through an unusual
      response element: implications for regulation of cell proliferation.
AB  - Cloning and sequence analysis of the 5'-flanking region of the human H1(0)
      histone gene, a differentiation-specific member of the H1 family, has revealed
      several potential regulatory elements. In this study, we have characterized the
      interactions of nuclear receptors with an unusual response element consisting of
      two half-sites arranged as a direct repeat with an 8-bp spacer (DR-8). Thyroid
      hormone receptors (TR) bind this DR-8 as homodimers and heterodimers with RXR.
      Retinoic acid receptors (RARs) also bind as heterodimers with RXR to the DR-8,
      and this binding is enhanced in the presence of retinoic acid (RA) and/or 9-cis
      RA. Reporter constructs containing the DR-8 allowed a several-fold induction by
      T3 in the presence of TRs. RAR alpha and RAR beta allowed RA-dependent
      transcriptional activation whereas RAR gamma mostly increased basal activity. 9
      cis RA inhibited the T3 response, indicating a hormonal cross-talk among the
      subfamily of nuclear receptors. Two orphan receptors, COUP-TF and v-erbA, also
      bind the DR-8 sequence in the human H1(0) promoter. COUP-TF, which usually
      represses RAREs, enhances transcriptional activation through the DR-8 whereas v
      erbA completely represses TR-RXR induction of the H1(0) gene. Thus, a number of
      signaling pathways that play important roles during development and
      differentiation are able to influence the transcription rate of this special H1
      subtype directly through a DR-8 response element in its promoter. Because H1(0)
      expression levels inversely correlate with cell proliferation, our data suggest
      that several nuclear receptors and the v-erbA oncogene can influence cell
      proliferation via the regulation of H1(0) expression.

PMID- 7576179
TI  - Identification of a silencer, enhancer, and basal promoter region in the human
      CD95 (Fas/APO-1) gene.
AB  - Genomic clones for the human CD95 (Fas/APO-1) and CD40 genes have been isolated
      and 2.3 kb of the CD95 and 0.8 kb of the CD40 gene 5'-flanking regions sequenced.
      Comparisons of the human CD95 gene with the human CD40 and the murine CD40 and
      TNFR-II genes showed a low degree of sequence similarity. However, dot matrix
      analyses revealed conservation of two stretches between human CD95 (-387 to -362
      and -288 to 261 in CD95) and murine TNFR-II genes. Additionally, TCCTCC motifs
      are present within 400 bp up-stream of the ATG of all genes examined. Repeated
      interferon-beta (IFN-beta) silencer B motifs and a lysozyme silencer 1 motif have
      been found in the CD95 gene at approximately -1,600 and -1,100, respectively.
      Sequence comparison of the 5'-flanking regions of the murine and human CD40 genes
      revealed the presence of a conserved AP-4 site and two SP-1 sites. CD95, CD40,
      and TNFR-II genes all lack classical TATA and CAAT boxes. However, a strongly
      increased frequency of CpG dinucleotides was found. Primer extension analysis
      revealed multiple transcriptional start sites in the CD95 gene, where the usage
      of individual start sites appeared to be cell type-specific. Functional analysis,
      using reporter constructs and transient transfections, identified a silencer
      activity residing between nucleotide positions -1,781 and -1007 and a strong
      enhancer region between -1,007 and -425 in the human CD95 gene. The region
      between -425 and -1 retained a basal promoter activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7576178
TI  - Unexpected transcriptional signals in normal and mitotically defective cells
      mediated through cytokine and growth factor receptors.
AB  - Polypeptide growth factors and cytokines mediate their biochemical functions
      through their responsive receptors. Known cytokine receptors do not possess
      intrinsic kinase domains whereas several polypeptide growth factor receptors do.
      Nevertheless, both classes of ligands are capable of activating sets of
      overlapping genes. In human epidermoid carcinoma cells, for example, both
      cytokines and epidermal growth factor (EGF) promote a common transcriptional
      activation signal through the tyrosine phosphorylation of stat91 (signal
      transducer and activator of transcription) proteins. The stat family of
      cytoplasmic proteins also appear to have dual functions. Tyrosine phosphorylated
      'stats' are employed for signal transduction and, second, for activation of
      transcription of several genes. The transcription factor-SIE-DNA binding patterns
      are now known to be different for EGF and interferon-gamma IFN-gamma-treated
      cells. Nevertheless, in the active DNA-bound complex, the stat91 polypeptide is a
      component found in either EGF or INF-gamma-treated extracts. Other stat family
      members of transcription factors may also be present in the complexes. In this
      case, tyrosine phosphorylated stat91 polypeptides may form into homodimeric or
      heterodimeric assemblies with other stat-related transcription factors. We
      describe a novel stat-related factor, p93, that is found in EGF-treated A431 cell
      extracts but appears to be absent in bovine fibroblast growth factor (bFGF), IFN
      gamma, tumor necrosis factor-alpha (TNF-alpha), and untreated cells. p93 appears
      to be antigenically related to stat91. p185c-neu+, EGFr+ (M1), and p185c-neu-
      kinase inactive, EGFr+ (NEN757) expressing cells undergo different mitotic
      responses to EGF. M1 can respond to EGF mitotically while NEN757 cannot. Both
      cell lines respond to 10 ng/ml of EGF and also to IFN-gamma in transducing
      transcriptional activation signals to the nucleus, despite the distinct growth
      response to EGF. Our work has analyzed the stat pathway in these types of cells
      and found similar patterns of usage despite the distinct EGF-responsive features.
      Cytoplasmic nonreceptor tyrosine kinases Jak1 and Jak2 may be involved in the
      activation of stat91 and other transcription factors in EGF and IFN-gamma
      signaling pathways. Collectively, these studies suggest that the major EGF
      stimulated mitotic growth pathways may not be absolutely linked to the stat91
      signaling pathways and that such transcription complexes are more complex than
      previously reported.

PMID- 7576180
TI  - Aspartic acid residue 124 in the third transmembrane domain of the somatostatin
      receptor subtype 3 is essential for somatostatin-14 binding.
AB  - A highly conserved aspartic acid residue present in the third membrane-spanning
      region of adrenergic and muscarinic receptors is directly involved in ligand
      binding. The five cloned somatostatin receptor subtypes also contain this residue
      at the same relative position. To test whether Asp-124 of the rat somatostatin
      receptor subtype 3 (SSTR3) is responsible for the binding of somatostain-14 (SST
      14), this amino acid residue was replaced by an asparagine or a glutamic acid by
      polymerase chain reaction (PCR)-mediated site-directed mutagenesis. Expression
      and binding activity of the wild-type and mutant receptor constructs were studied
      in COS and HEK cells by ligand binding, UV cross-linking, Western blot, and
      immunocytochemical analysis. The Asn or Glu mutations result in a significant
      loss of SST-14 binding, although the mutant receptors are correctly transferred
      to the cell surface, demonstrating that Asp-124 is directly involved in binding
      of SST-14.

PMID- 7576181
TI  - Expression of the human T-cell receptor V beta 5.3 in Escherichia coli by thermal
      induction of the trc promoter: nucleotide sequence of the lacIts gene.
AB  - We have constructed a vector, pKBi, for the high-level expression of the variable
      beta chain 5.3 (V beta 5.3) of the human T-cell receptor in Escherichia coli.
      This vector incorporates the trc promoter, a polylinker, two transcription
      terminators, and the tetracycline resistance gene. Furthermore, the vector
      contains the lacIts gene that encodes a temperature-sensitive (ts) lac repressor,
      thus obviating both the need to use IPTG as a transcriptional inducer, and
      bacterial strains that harbor either the lacI or lacIq genes. The sequence of the
      lacIts gene shows an open reading frame of 1,080 nucleotides encoding 360 amino
      acids, and differs from the lacI gene at nucleotide 559 (with reference to the
      first nucleotide of the start codon). This nucleotide changes from G to A,
      causing amino acid residue 187 to change from glycine (GGC) to serine (AGC). This
      mutation imparts thermal sensitivity to the lac repressor protein. This is the
      first time that a TCR V beta region has been expressed at high levels (up to 28
      mg/liter of culture) without fusion partners. The availability of the lacIts gene
      for thermal induction of the trc promoter, and the presence of the tetracycline
      resistance gene should make the expression vector pKBi particularly attractive
      for the efficient production of human therapeutic proteins in bacteria.

PMID- 7576182
TI  - Characterization of four new tcp-1-related cct genes from the nematode
      Caenorhabditis elegans.
AB  - In this report we present the sequences of four new cct chaperonin genes from the
      nematode Caenorhabditis elegans. The four genes, cct-2, cct-4, cct-5, and cct-6
      are orthologs of the mouse chaperonin genes Cctb, Cctd, Ccte, and Cctz, sharing
      66%, 63%, 68%, and 67% deduced amino acid sequence identity, respectively. The C.
      elegans multigene family includes these four genes as well as cct-1 (tcp-1), and
      displays 23-35% pairwise predicted amino acid sequence identity between members,
      and 31-35% identity to the closely related archaebacterial chaperonin TF55. The
      five C. elegans cct genes are expressed in all life stages (egg, four larval
      stages, and adult). Members of the multigene family occur as a loosely associated
      group of three genes on chromosome II, and two widely separated genes on
      chromosome III. The predicted secondary structures of all five C. elegans CCT
      deduced protein sequences are nearly identical. Moreover, all chaperonins
      examined had comparable predicted secondary structures. Algorithmic predictions
      of the secondary structures of GroEL, Hsp60, and Rubisco subunit-binding protein
      (RuBP) are almost identical, and are very similar to the known GroEL secondary
      structure. The CCT/TF55 family predicted secondary structures are essentially
      identical to each other and are also related to GroEL, Hsp60, and RuBP. The most
      notable difference between the CCT/TF55 and the GroEL/Hsp60/RuBP families is in
      the presumed polypeptide binding domain.

PMID- 7576183
TI  - Binding of a CTF/NF1-like protein to the mouse colony-stimulating factor-1 gene
      promoter.
AB  - Circulating and tissue-specific monocytes/macrophages, through production of
      hydrolytic enzymes and growth factors, can dramatically affect the local tissue
      environment. Colony-stimulating factor-1 (CSF-1) is a key regulator of
      monocyte/macrophage cell activity. CSF-1 is produced by stromal elements,
      including fibroblasts, which are found in all tissues. To understand at the
      molecular level how changes in CSF-1 gene transcription are initiated in
      fibroblasts, we set out to identify the cis-acting elements and cognate trans
      acting factor(s) that bind regulatory regions of the mouse CSF-1 gene. Analysis
      of heterologous reporter constructs containing the mouse CSF-1 promoter linked to
      the bacterial chloramphenicol acetyltransferase (CAT) gene in transiently
      transfected fibroblasts identified a cis-acting element located between base
      pairs -88 and -43 of the CSF-1 gene. Electrophoretic mobility-shift assays
      (EMSAs) and DNase I protection assays with nuclear extracts isolated from
      proliferating fibroblasts revealed distinct protein binding to the region
      spanning base pairs -90 to -68. Results from methylation interference assays
      suggest CTF/NF1 or a CTF/NF1-like factor is the cognate trans-acting factor.
      Mutation of the putative CTF/NF1 binding site in the CSF-1 promoter lead to a
      modest decrease in promoter activity in transiently transfected fibroblasts and
      monocytes. Therefore, we have demonstrated that CTF/NF1 or a CTF/NF1-like protein
      binds to the CSF-1 gene promoter; however, binding of the CTF/NF1-like protein
      alone does not significantly effect changes in CSF-1 gene promoter activity.

PMID- 7576184
TI  - Developmentally regulated mouse gene NK10 encodes a zinc finger repressor protein
      with differential DNA-binding domains.
AB  - Using oligonucleotides complementary to the conserved inter-finger region of a
      variety of previously described zinc finger-encoding genes, a novel mouse gene
      was cloned and characterized. The gene is localized on chromosome 8 and comprises
      five exons. Its corresponding mRNA is developmentally regulated in various
      tissues and includes an open reading frame encoding a protein of 72,422 daltons.
      It shares amino-terminal homologies with human KRAB (or FPB) boxes, and contains
      13 zinc fingers of the C2-H2 type. The NK10 KRAB domains exhibit repressing
      activity when tested in GAL4 fusion protein assays. Cloning of putative target
      sequences revealed that the individual domains differentially contribute to zinc
      dependent target DNA binding.

PMID- 7576185
TI  - [Prevention of cholera transmission: rapid evaluation of the quality of municipal
      water in Trujillo, Peru].
AB  - Unboiled, unchlorinated drinking water is known to have been associated with
      epidemic transmission of cholera in Trujillo, Peru, in February 1991. In
      September of that same year, chlorination of the main water supply system was
      begun. Water quality in Trujillo at the central level is monitored at dams and
      principal distribution points, but the effects of this surveillance on the
      quality of the water distributed are not known. In order to evaluate water
      quality in the residential areas of Trujillo, water samples were collected in
      February 1993 from 30 systematically selected houses. The chlorine levels in the
      samples were measured, and cultures for coliform bacteria were done. The free
      chlorine concentration varied from 0 to 1.5 mg/L (median = 0.4 mg/L). No free
      chlorine was detected in 5 samples (17%), and in 14 (47%) the concentrations were
      less than 0.4 mg/L. Coliforms were found in 16 samples (53%), but none were fecal
      coliforms. These results demonstrate the wide variability in chlorine
      concentrations in the municipal water that is distributed to dwellings. This
      variability, together with the need to store drinking water in the house because
      of shortages, supports the recommendation of the Ministry of Health that
      residents should treat drinking water in their homes. The simple sampling
      framework employed in this study provided a rapid evaluation of the quality of
      municipal water supplied to consumers. Similar studies could be carried out
      easily in other metropolitan areas where water quality is suspect, in order to
      rapidly obtain essential information on water quality at the level of the
      consumer.

PMID- 7576187
TI  - [Characteristics of drug acquisition in Morelia (Michoacan), Mexico].
AB  - This cross-sectional, descriptive study was carried out in Morelia, Mexico, to
      find out the extend to which the public was buying essential drugs and other
      pharmaceuticals whose sale is prohibited or strictly regulated in other
      countries, and to determine the magnitude of the practice of self-medication.
      Customers buying drugs at 54 pharmacies were interviewed during peak shopping
      hours. The mode of acquisition of the drugs was classified as self-medication,
      medical prescription, or prescription from pharmacy salesperson, and the drugs
      were grouped as essential or nonessential. Products that are prohibited or
      greatly restricted in other countries were also identified. The most frequently
      bought products were analgesics and nonsteroidal anti-inflammatory drugs,
      vitamins, broad-spectrum antibiotics, steroids, cold and flu medications, narrow
      spectrum antibiotics, and benzodiazepines. Of 1388 products sold, 394 (28.4%)
      appear on the list of essential drugs. The mode of acquisition was self
      medication for 51.4% of the sales, medical prescription for 35.6%, and
      recommendation of a pharmacy employee for 13%. In addition, 14.3% of the products
      bought were prohibited or restricted in other countries. The results highlighted
      the need for greater precision in the General Health Law of Mexico with regard to
      regulation of drug sales. The results also imply the need for other actions,
      namely, educational campaigns directed to the general population to discourage
      self-medication; Strengthening of coordination between government and the
      pharmaceutical industry; improvement in the availability of and information on
      generic drugs; and modification of pharmacological training programs.

PMID- 7576186
TI  - [Fluoride content of table salt in Mexico City].
AB  - The fluoride content of a sample of bags of salt for sale in Mexico City was
      measured in order to estimate the proportion of marketed salt that contained the
      quantity of fluoride set by the National Program for Prevention of Dental Caries
      through Consumption of Fluoridated Table Salt. The effectiveness of that program
      had never been evaluated. In March 1993, bags of salt were obtained from 70 of
      the 3544 neighborhoods that make up Mexico City. The stores were selected by
      simple random sampling. Salt was likewise purchased from 20% of the 146
      supermarkets and self-service stores in the city, also selected as a random
      sample. Then, blind measurement was done of the fluoride content of 221 bags of
      salt. The true content of this element was often found to be below the amount
      called for by the government. In addition, it did not coincide with the quantity
      indicated on the package label, which is a violation of the law.

PMID- 7576189
TI  - ["Razon relativa" and "tasa relativa" as translations of odds ratio and hazard
      ratio].

PMID- 7576188
TI  - [Critical analysis of drug policy in Brazil].

PMID- 7576190
TI  - [The audiometric evaluation of Buenos Aires schoolchildren].
AB  - This cross-sectional study, which was carried out between 3 May and 30 September
      1993, involved examination with a pediatric otoscope of a random sample of 100
      first-grade schoolchildren in a Buenos Aires hospital, followed by tonal
      audiometry and tonal sweep in 90 of those children. The objectives of the study
      were to discover the frequency of hearing disorders and to evaluate the
      importance of audiometric screening in the child population. The results were
      classified according to the type (conduction or perception) and degree (mild,
      moderate, or severe) of hypoacusis, which was detected in 36 children (39%). Of
      those affected, 35 had mild or moderate conduction hypoacusis (loss of less than
      31 decibels [dB] or less than 41 dB, respectively). No case of severe hypoacusis
      was found. The authors consider that audiometric screening of children entering
      primary school is justified by the high frequency of preventable hearing problems
      and by the repercussions that those problems can have on speech and learning.

PMID- 7576191
TI  - [Tobacco and periodontopathies].
AB  - The purpose of this research, which is part of a study on periodontal disease and
      its risk factors among workers in Araraquara, Sao Paulo, Brazil, was to determine
      the association between smoking and its frequency, on the one hand, and the
      presence of periodontal cavities on the other. A sample of 528 sugar and alcohol
      refinery employees from Araraquara between the ages of 18 and 64 was examined in
      March and April of 1992 by a trained examiner who applied the Index of
      Periodontal Treatment Needs in the Community. Questionnaires were used to record
      the individuals' age, smoking habits, and the number of cigarettes smoked daily.
      An oral examination was also performed to assess the presence of dental plaque
      and to determine the bacterial colony index. Data analysis revealed a positive
      association between the presence of periodontal cavities and smoking. After
      adjusting the data for age, presence of dental plaque, and bacterial colony
      index, the odds ratio for having periodontal cavities increased directly with the
      number of cigarettes smoked. These results suggest that smoking and its frequency
      should be taken into account when planning programs for the primary prevention
      and treatment of periodontal disease.

PMID- 7576193
TI  - Glucose-6-phosphate dehydrogenase deficiency.

PMID- 7576192
TI  - [The use of the microcomputer in selecting the basic cause of death].
AB  - The article begins with a discussion of some mortality statistics issues,
      problems encountered in the manual selection of underlying cause of death, and
      also the increasing need for information on associated causes. These
      circumstances led the National Center for Health Statistics to develop the
      computerized ACME System, which has been in use in Sao Paulo State since 1983.
      The ACME System's requirement of a mainframe computer, as well as other
      operational limitations, has prevented its installation throughout the country.
      In order to standardize and improve the quality of mortality data in Brazil, the
      Informatics Department of the Ministry of Health's National Health Foundation and
      the World Health Organization (WHO) Collaborating Center for the Classification
      of Diseases in Portuguese developed the microcomputer-based Underlying Cause
      Selection System (SCB) in 1993. This is an expert system that employs artificial
      intelligence techniques to reproduce the reasoning of a coder in selecting the
      underlying cause of death, according to the rules and provisions of the Ninth
      Revision of the International Classification of Diseases. The SCB has a very user
      friendly interface, occupies 2.6 megabytes of hard disk space, and can run on any
      386 or higher XT or AT computer. In addition to selecting the underlying cause of
      death, the system stores data on associated conditions.

PMID- 7576195
TI  - Clinical heterogeneity reflects biologic diversity in chronic lymphocytic
      leukemia.
AB  - As the incidence of B cell chronic lymphocytic leukemia increases in an aging
      population, it becomes more important to re-evaluate our understanding of the
      disease process and current therapy. Previous treatment strategies have been, for
      the most part, unsuccessful in prolonging survival and thus new approaches are
      needed. More intense cellular and molecular research on the biologic diversity of
      this neoplasm will further our understanding of the causes of clinical
      heterogeneity and refine our ability to predict progression. New approaches,
      based on alterations of neoplastic cell growth by cytokines or chemotherapeutic
      agents, may enable clinicians to 'customize' individual treatments based on the
      stages of CLL B cell differentiation and our understanding of factors involved in
      the regulation of apoptosis and proliferation at those stages. Taken together,
      these efforts should ultimately yield much new information that will lead to
      reduced morbidity and mortality in B-CLL, the most common form of human leukemia.

PMID- 7576196
TI  - Megakaryocytopoiesis: cellular aspects and regulation.

PMID- 7576194
TI  - The hepatocyte nuclear factor-3/forkhead transcription regulatory family in
      development, inflammation, and neoplasia.
AB  - HNF-3/FKH genes are a large family of transcriptional activators. They are
      expressed in specific developmental and tissue patterns. Indeed, several of them
      are known to be essential for normal development (e.g. Dfkh and slp-1,2).
      Mutation within one of these genes produces mutant fruitfly embryos that are
      unable to survive. This family shares conserved DNA binding and transcriptional
      activation domains. The DNA binding domain has been crystallized, and its
      structure determined. Although it has resemblance to helices of homeodomains and
      H5 histones, it represents a new DNA binding motif, which has been called the
      'winged helix,' because it contains additional interactive peptide regions called
      termed wings. Subtle amino acid variations in a region adjacent to the DNA
      recognition helix influence the recognition specificity of each HNF-3/FKH protein
      and therefore confer selectivity in promoter regulation. Members of this family
      are important in regulating the inflammatory response of the liver (the three HNF
      3 genes). In addition, several members may be important in blood cell development
      (H3 and 5-3). Finally, two of these genes have been found to produce neoplasia
      (qin and FKHR). As investigation progresses, the mechanism by which these genes
      regulate development, inflammation and neoplasia will become more clear.

PMID- 7576198
TI  - The role of chemotherapy in osteogenic sarcoma.

PMID- 7576197
TI  - Treatment of advanced epithelial ovarian cancer: past, present and future.

PMID- 7576199
TI  - Advances in the treatment of meningeal cancers.

PMID- 7576200
TI  - Angiogenesis and cancer metastases: therapeutic approaches.

PMID- 7576201
TI  - Advances in glyoxalase research. Glyoxalase expression in malignancy, anti
      proliferative effects of methylglyoxal, glyoxalase I inhibitor diesters and S-D
      lactoylglutathione, and methylglyoxal-modified protein binding and endocytosis by
      the advanced glycation endproduct receptor.

PMID- 7576202
TI  - Hippocampal and nonhippocampal contributions to place learning in rats.
AB  - Brain structures thought to be critical for learning and memory were lesioned,
      and the effects on rats' ability to locate food on a radial maze in situations
      that provided different types of information was used to suggest general
      principles of information processing by hypothesized neural systems that include
      each of the lesioned structures. When animals were confined to food-containing
      and empty arms on different training trials, the learned discrimination between
      the arms was amygdala based. More training trials were required for ambiguous
      (adjacent arms) than for unambiguous (widely separated arms) discriminations.
      When rats moved around and entered both food and no-food arms on the same trial,
      the unambiguous discrimination was learned by both dorsal striatum- and
      hippocampus-based systems; however, the ambiguous discrimination was learned only
      by the hippocampus system.

PMID- 7576203
TI  - Fornix-fimbria section and working memory deficits in rats: stimulus complexity
      and stimulus size.
AB  - Rats were trained on delayed matching-to-sample (DMS) with goalboxes containing
      complex objects as stimuli. On reaching the preoperative learning criterion, the
      rats were allocated to conventional fornix-lesioned or control groups. In a
      series of postoperative DMS experiments, different kinds of stimuli were used,
      ranging from complex object boxes to large, simple black or white goalboxes, with
      3 transitional types in between. Lesions impaired choice accuracy whenever the
      rats were tested with large, simple goalboxes, but not with smaller boxes of
      otherwise identical construction. A brief, final experiment showed no
      amelioration of the lesion-induced impairment when complex objects were added to
      large, simple goalboxes. The results are discussed in terms of spatial and
      nonspatial accounts of hippocampal function.

PMID- 7576204
TI  - Rats with fimbria-fornix lesions can acquire and retain a visual-tactile
      transwitching (configural) task.
AB  - The idea that the hippocampus is essential for acquisition and retention of a
      transwitching (configural) problem is evaluated with a visual-tactile task. The
      task requires the rats to pull up a string of one of two sizes for food, as
      signalled by room lighting conditions. Rats received cathodal fimbria-fornix
      lesions either prior to or after learning the task. Rats with fimbria-fornix
      lesions were unimpaired in acquisition or retention. The results do not support
      the position that the hippocampal formation is essential for the acquisition and
      retention of a transwitching configural problem. The result is discussed in
      relation to the configural theory of hippocampal function.

PMID- 7576206
TI  - Lesions of rat perirhinal cortex exacerbate the memory deficit observed following
      damage to the fimbria-fornix.
AB  - Rats that had received bilateral lesions of the perirhinal cortex, fimbria
      fornix, combined lesions of both these structures, or sham operations were tested
      on an object-guided delayed non-match-to-sample task. Perirhinal lesioned and
      fimbria-fornix lesioned rats were moderately impaired when delay intervals of 30
      s or more were introduced between the sample and test phases of the experiment.
      Animals with combined lesions displayed a considerably greater impairment than
      animals with lesions of either structure alone. The combined lesioned animals
      were severely impaired in the initial acquisition of the task and displayed a
      profound memory deficit at delay intervals of greater than 4 s. These results
      emphasize the importance of the perirhinal cortex to memory function and suggest
      that the perirhinal cortex and the hippocampal formation may function
      interactively in the execution of memory processes.

PMID- 7576205
TI  - Disruptive effects of posttraining perirhinal cortex lesions on conditioned fear:
      contributions of contextual cues.
AB  - Lesions placed in the rostral perirhinal cortex (rPRh) after fear conditioning
      interfere with the expression of conditioned fear responses elicited by auditory
      and visual conditioned stimuli when these stimuli are presented in a context that
      differs from the conditioning context. The present study examined whether lesions
      of the rPRh have similar effects when animals are tested in the conditioning
      context. Two days after male rats received classical fear conditioning, involving
      the pairing of an auditory conditioned stimulus (CS) with footshock, bilateral
      electrolytic lesions were produced in the rPRh. Five days later conditioned
      freezing behavior was measured during a 60-s exposure to the CS in a novel
      context and then 1 hr later in the conditioning context. There were 3 major
      findings. First, rPRh-lesioned animals froze significantly less than controls to
      the CS in the novel context, thus confirming previously reported findings.
      Second, rPRh-lesioned animals also froze less than controls to the CS in the
      conditioning context, but froze significantly more to the CS in the conditioning
      than in the novel context, suggesting that at least part of the deficit in the
      novel context is due to the absence of contextual cues. Third, animals with rPRh
      lesions froze significantly less than controls to the conditioning context
      itself. This latter finding suggests that rPRh lesions interfere with contextual
      processing and that the improvement of performance in the conditioning context
      might have been even greater had lesioned animals been able to fully process
      contextual cues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576207
TI  - Effects of a microinjection of morphine into the amygdala on the acquisition and
      expression of conditioned fear and hypoalgesia in rats.
AB  - A unilateral microinjection of morphine into the amygdala impaired the
      acquisition of fear and hypoalgesic responses in rats exposed to a heated floor
      in a hot-plate apparatus. This impairment was dose dependent, receptor specific,
      and not observed in rats microinjected with morphine into the caudal basolateral
      amygdala. A microinjection of morphine into the amygdala reduced the expression
      of fear responses and of naloxone-sensitive hypoalgesic responses, but did not
      reduce the expression of naloxone-insensitive hypoalgesic responses. The results
      document an involvement of opioidergic mechanisms in the amygdala in learned
      danger and of the amygdala in the control of opioid hypoalgesic responses. They
      also suggest that learned danger can activate antinociceptive mechanisms
      independently of the amygdala.

PMID- 7576208
TI  - Differential effects of pretraining inactivation of the right or left amygdala on
      retention of inhibitory avoidance training.
AB  - Rats with bilateral cannulas aimed at the amygdalae received bilateral infusions
      of either buffer or lidocaine hydrochloride, or unilateral infusions of each, 5
      min before continuous multiple-trial inhibitory avoidance (CMIA) training.
      Retention was tested 48 hr later. Some of the rats were retrained at this time
      and tested again 48 hr later. Bilateral infusions of lidocaine prior to the
      initial training impaired acquisition, retention, and relearning of the CMIA
      task. Unilateral infusions of lidocaine into the right or left amygdala did not
      affect acquisition. Rats given lidocaine into the right amygdala were impaired on
      retention 48 hr later. The findings are consistent with others indicating
      involvement of the amygdala in acquisition and consolidation of aversively
      motivated learning and suggest possible differential involvement of the right and
      left amygdalae in memory consolidation.

PMID- 7576210
TI  - Taste-potentiated odor conditioning: impairment produced by infusion of an N
      methyl-D-aspartate antagonist into basolateral amygdala.
AB  - Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA)
      receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated
      odor conditioning: a form of learning that is dependent on information processing
      in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired
      in their acquisition of the potentiated learning to an odor cue. Expression of
      this learning and acquisition of a simple taste aversion remained intact
      following drug treatment. In Experiment 2, dose dependence and stereoselectivity
      were demonstrated for the antagonist compound. These results are consistent with
      previous studies demonstrating that either basolateral amygdala lesions, or
      treatment with NMDA antagonists, by other routes (systemic or intraventricular)
      produce selective deficits in taste-potentiated odor conditioning.

PMID- 7576209
TI  - Pavlovian conditional vocalizations of the rat: a model system for analyzing the
      fear of pain.
AB  - Presentation of a 6-s light conditional stimulus (CS) that overlapped with a 1-s
      tailshock unconditional stimulus (US) generated audible conditional vocalization
      responses (VCRs) during the CS period. The rate of conditioning was observed to
      be directly related to the intensity of the tailshock US (0.15 mA-0.80 mA). The
      amplitude, duration, and number of VCRs was also directly related to US
      intensity, whereas the latency of VCRs from CS onset was inversely related to US
      intensity. VCRs were not observed in rats given explicitly unpaired presentations
      of CS and US (0.80 mA). The capacity of tailshock to support development of VCRs
      was found to depend on its capacity to elicit vocalization afterdischarges
      (VADs). Sonographic analysis of vocalizations revealed that VCRs and VADs share
      spectrographic characteristics. Results are discussed in terms of VCRs' providing
      a model system for analyzing the fear of pain and its suppression.

PMID- 7576211
TI  - Fear-potentiated startle and electrically evoked startle mediated by synapses in
      rostrolateral midbrain.
AB  - Startle amplitudes are increased when acoustic startle responses are elicited in
      the presence of a stimulus that has previously been paired with shock. This "fear
      potentiated" startle response appears to be mediated via the caudal ventral
      amygdalofugal pathway to the brainstem. Electrical stimulation of this pathway
      evokes unconditioned startlelike responses. Collision tests have shown that a
      monosynaptic connection from amygdala to midbrain mediates these responses.
      Collision tests here localize these synapses mediating electrically evoked
      startlelike responses to the rostrolateral midbrain in awake rats. To test
      whether rostrolateral midbrain synapses also mediate fear-potentiated startle, we
      lesioned cells in these sites with ibotenic acid. These lesions completely
      blocked fear potentiation of acoustic startle. These same lesions did not block
      potentiation of startle by d-amphetamine (6 mg/kg).

PMID- 7576213
TI  - Functionally distinct memories for imprinting stimuli: behavioral and neural
      dissociations.
AB  - Precocial chicks exposed to a stimulus subsequently approach that stimulus in
      preference to other, novel stimuli. Previous investigations of the neural basis
      of these imprinting preferences suggest that imprinting training results in the
      formation of two memories. The first memory is formed rapidly and is located in
      the intermediate and medial part of the hyperstriatum ventrale (IMHV) of the left
      hemisphere; the formation of the second, in another memory system, S', takes
      several hours and can be prevented by a lesion placed in the right IMHV soon
      after training. The results of the present study suggest that the functional
      characteristics of these memories differ. Although memories in both left IMHV and
      S' supported imprinting preferences (Experiments 1a and 2a), only memories in S'
      influenced the acquisition of a heat-reinforced discrimination in which imprinted
      objects served as discriminanda (Experiments 1b and 2b).

PMID- 7576212
TI  - Differential contribution of dorsal and ventral medial prefrontal cortex to the
      acquisition and extinction of conditioned fear in rats.
AB  - The emotional reactivity of rats with lesions of the dorsal portion of medial
      prefrontal cortex (mPFC) was examined using a classical fear conditioning
      paradigm. Conditioned fear behavior (freezing responses) was measured during both
      the acquisition and extinction phases of the task. Lesions enhanced fear
      reactivity to both the conditioned stimulus (CS) and contextual stimuli during
      both phases, suggesting that dorsal mPFC lesions produce a general increase in
      fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski,
      and J. E. LeDoux (1993) found that lesions just ventral to the present lesions
      had no effect during acquisition of the same task and prolonged the fear response
      to the CS (but not the context) during extinction. Thus, both dorsal and ventral
      regions of mPFC are involved in the fear system, but each modulates different
      aspects of fear responsivity.

PMID- 7576214
TI  - Acquisition, retention, and extinction of operant discriminations in rats with
      nucleus basalis magnocellularis lesions.
AB  - Effects of bilateral ibotenic acid lesions of nucleus basalis magnocellularis
      (NBM) and scopolamine treatment on different aspects of learning and memory in an
      operant discrimination task were assessed. In Experiment 1, NBM lesions impaired
      acquisition performance. In Experiment 2, scopolamine lowered response rates but
      did not affect discrimination accuracy in lesioned or control rats. In Experiment
      3, although pretrained rats showed transient increases in commission errors,
      percentage correct responding remained above chance levels after lesion. During
      extinction in Experiment 4, operant responding diminished more quickly in
      pretrained NBM-lesioned rats than in controls, but subsequent reacquisition
      performance was equivalent in both groups. Results suggest the NBM is importantly
      involved in discrimination learning, but cholinergic activity may be less
      critical for memory retention than for acquisition.

PMID- 7576216
TI  - Amphetamine-induced conditioned activity in rats: comparison with novelty-induced
      activity and role of the basolateral amygdala.
AB  - A within-subject design was used to investigate the behavioral and neural basis
      of the conditioned activity induced by amphetamine in male Wistar rats. In this
      design, conditioned activity was inferred when the activity of a given rat
      following a vehicle injection was greater in its amphetamine-paired environment
      (CS+) than in its vehicle-paired environment (CS-). Conditioned activity (a) did
      not change in magnitude with the number of conditioning sessions, (b) did not
      differ from the level of activity recorded during the first exposure to the CS-
      (novelty), (c) had an extinction rate that was similar to the rate of habituation
      to the CS-, and (d) was not impaired by a bilateral excitotoxic lesion of the
      basolateral amygdala. Results are discussed in light of the incentive
      conditioning and habituation theories of conditioned activity.

PMID- 7576215
TI  - Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on
      learning and memory in rats.
AB  - Male Long-Evans rats were given injections of either 192 IgG-saporin, an
      apparently selective toxin for basal forebrain cholinergic neurons (LES), or
      vehicle (CON) into either the medial septum and vertical limb of the diagonal
      band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and
      substantia innominata (nBM/SI). Place discrimination in the Morris water maze
      assessed spatial learning, and a trial-unique matching-to-place task in the water
      maze assessed memory for place information over varying delays. MS/VDB-LES and
      nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the
      place discrimination, but were mildly impaired relative to CON rats in
      performance of the memory task even at the shortest delay, suggesting a
      nonmnemonic deficit. These results contrast with effects of less selective
      lesions, which have been taken to support a role for basal forebrain cholinergic
      neurons in learning and memory.

PMID- 7576217
TI  - Effects of prenatal exposure to cocaine on Morris water maze performance in adult
      rats.
AB  - The spatial memory of adult rats prenatally exposed to cocaine and that of
      control offspring was assessed using the Morris water maze. Offspring were
      derived from Sprague Dawley dams that received subcutaneous injection of 40
      mg/kg/3 cc cocaine hydrochloride (C40) daily on gestational Days 8-20, pair-fed
      dams injected with saline, or nontreated control dams. After acquisition, the
      platform was moved to a new location (reversal phase). Probe trials were
      conducted at the end of acquisition and reversal training. On the 1st acquisition
      day, adult male and female offspring prenatally exposed to cocaine required
      significantly more time and traversed a greater distance to find the hidden
      platform than did control offspring. Despite these initial differences observed
      in C40 offspring performance, all of the rats were performing at equivalent
      levels at the time probe trials were conducted.

PMID- 7576218
TI  - Isolation disrupts retention in preweanling rat pups.
AB  - Expression of an olfactory memory in 18-day-old rat pups was examined in eight
      experiments following brief manipulations of environmental conditions prior to a
      retention test. In the first experiment we found that retention was disrupted if
      a pup was placed in isolation for 3 hr prior to the retention test. The retention
      deficit persisted even when pups had 3-hr exposure to an anesthetized dam and
      siblings before testing. However, there was no deficit in retention if pups spent
      the pretest interval with a nonlactating foster dam, their father, or
      littermates. Finally, we found that this deficit in retention could be alleviated
      by cuing treatments that preceded the retention test following isolation. Both
      discrete cues used during training and returning the pup to the home cage with
      parents and siblings for 3 hr were found to alleviate the retention deficit
      caused by isolation. These data demonstrate that housing conditions can influence
      postacquisition memory processes in the young animal.

PMID- 7576219
TI  - The dorsal raphe nucleus is a site of action mediating the behavioral effects of
      the benzodiazepine receptor inverse agonist DMCM.
AB  - Systemic administration of benzodiazepine receptor inverse agonists leads to
      behavioral changes similar to those produced by inescapable shock (IS). The
      dorsal raphe nucleus (DRN) is a critical structure mediating IS effects. The
      present experiments determined whether the DRN is a site mediating the behavioral
      changes produced by benzodiazepine receptor inverse agonists. Microinjection of
      the inverse agonist Methyl 6,7-Dimethoxy-4-ethyl-beta-carboline-3-carboxylate
      (DMCM) in the region of the DRN produced enhancement of fear conditioning as
      assessed by the amount of freezing in the presence of shock cues as well as
      interference with shuttlebox escape learning assessed 24 hr later. Furthermore,
      lesion of the DRN blocked the effects of systemic DMCM on fear conditioning and
      escape learning. These data suggest that the DRN is indeed critical in mediating
      these behavioral consequences of DMCM and further support a role for the DRN in
      producing the behavioral changes induced by IS.

PMID- 7576220
TI  - Effects of exposure to stressors of varying predictability on adrenal function in
      rats.
AB  - For 5 days, rats were exposed to shocks that were signalled by a light 0, 33, 66,
      or 100% of the time. Basal hormone levels and responses to a light-shock pair
      were measured daily. Greater predictability was associated with higher basal
      plasma corticosterone and norepinephrine levels indicative of chronic stress.
      Habituation of the corticosterone response was also less in the groups with
      greater predictability. However, predictability did not affect plasma prolactin
      or epinephrine responses. Because the endocrine systems responded differently, it
      is unlikely that the changes were due to a unitary process. Greater
      predictability appeared to be more stressful in this paradigm. Both associative
      and nonassociative factors have major roles in determining the hormonal responses
      to repeated presentation of stressors.

PMID- 7576223
TI  - Computational and entrainment models of circadian food-anticipatory activity:
      evidence from non-24-hr feeding schedules.
AB  - Rats anticipate a daily meal, provided that meal onset intervals are within a
      circadian (22-31 hr) range. Food-anticipatory activity (FAA) has been interpreted
      as evidence for a food-entrained circadian pacemaker or for a computational
      process that uses stored representations of pacemaker phase. The models make
      different predictions concerning the symmetry and history dependence of the
      circadian limits to FAA. To test those predictions, rats were entrained to 24-hr
      light-dark and feeding cycles and then exposed to feeding cycles of 21, 22, 25,
      26, or 27 hr. Rats showed strong FAA to feeding cycles > or = 24 hr, but not to
      schedules < 24 hr. Prior exposure to long cycles did not promote anticipation
      under short cycles. Meal omission tests confirmed that failure to observe FAA to
      < 24-hr feeding cycles was not a result of masking by early mealtimes. These and
      other aspects of the results are consistent with the entrained oscillator model
      of FAA.

PMID- 7576221
TI  - Poststimulation excitability of ventral pallidum self-stimulation neurons.
AB  - The degree of neural recovery from refractoriness was inferred in rats self
      stimulating with pairs of pulses in the ventral pallidum. The prerecovery
      intrapair interval varied from 0.5 to 1.0 ms, depending on brain site. At some
      sites, recovery reached its maximum within less than 1.6 ms whereas, at the
      majority of sites, a substantial amount of recovery occurred at delays longer
      than 1.2 ms. The shortest recovery estimates were not fundamentally different
      from those obtained from sites lying along the medial forebrain bundle. The
      longest recovery estimates were similar to those obtained from cortical and basal
      forebrain sites. The differences in recovery noted between sites and the presence
      of step-like patterns in the recovery curves suggest the presence of neural
      heterogeneity within the ventral pallidal substrates of reward.

PMID- 7576222
TI  - A gender-specific mechanism for pair bonding: oxytocin and partner preference
      formation in monogamous voles.
AB  - Previous studies have demonstrated that central administration of vasopressin but
      not oxytocin facilitates pair bonding in the monogamous male prairie vole. This
      study tested vasopressin and oxytocin in the formation of the female vole's
      preference for a particular male partner. Initial studies showed that in
      monogamous female prairie voles (but not in nonmonogamous congeners), mating was
      followed by a partner preference that endured for at least 2 weeks. Nonmating
      prairie vole females developed a partner preference following oxytocin infusions,
      but not after vasopressin or cerebrospinal fluid infusions. Females given a
      selective oxytocin antagonist showed normal mating behavior, yet failed to
      develop a partner preference. The vasopressin antagonist failed to block partner
      preference formation in mated females. These results suggest that oxytocin,
      released with mating, may be critical to formation of a partner preference in the
      female prairie vole; this contrasts to vasopressin, which appears to be more
      important for pair bonding in the male of this species.

PMID- 7576224
TI  - The CS-US interval and taste aversion learning: a brief look.
AB  - Temporal parameters of taste aversion learning are known to differ markedly from
      other learning paradigms in that acquisition occurs despite lengthy delays
      between exposure to conditioned (CS) and unconditioned stimulus (US). Far less
      consideration has been paid to very brief CS-US intervals and the possibility
      that this learning may also be distinguished by an ineffectiveness of close
      temporal contiguity between CS and US. The effectiveness of a very brief CS-US
      interval (10 s) was compared with that of 2 lengthier intervals (15 and 30 min).
      Temporal control of CS delivery (0.15% saccharin solution) into the oral cavity
      and US delivery (7.5 mg/kg apomorphine hydrochloride) into circulation involved
      infusion pumps and indwelling catheters. Using a 1-trial learning paradigm, CS-US
      delays of 15 and 30 min led to significant aversions whereas the 10-s CS-US
      interval did not, suggesting that close temporal contiguity between CS and US is
      neither necessary nor sufficient for conditioned taste aversion acquisition.

PMID- 7576225
TI  - Spared retention of inhibitory avoidance learning after posttraining amygdala
      lesions.
AB  - Previous findings indicate that the memory-impairing effects of posttraining
      amygdala lesions are attenuated by increasing the number of training trials given
      prior to the induction of the lesion. The aim of this experiment was to determine
      whether the degree of impairment is also influenced by the footshock intensity
      used during training. Rats were given 1 trial of inhibitory avoidance (IA)
      training with either no footshock or a footshock at 1 of 3 intensities. Sham or
      neurotoxic amygdala lesions were induced 1 week later. On a retention test
      performed 4 days after surgery, the performance of all amygdala-lesioned rats
      given footshock training, including those given the lowest training footshock,
      was better than that of amygdala-lesioned rats given no training footshock. These
      findings of preserved retention of IA learning in rats given posttraining
      amygdala lesions do not support a general hypothesis that the amygdala is a locus
      of permanent changes underlying aversively motivated learning.

PMID- 7576226
TI  - Asymmetries in spontaneous head orientation in infant chimpanzees (Pan
      troglodytes).
AB  - Behavioral laterality in head orientation while sleeping in either a supine or
      prone posture was examined in 43 chimpanzees (Pan troglodytes) for the first 3
      months of life. An overall significant right-side lateral bias was found for head
      orientation in the supine posture. A trend toward greater right-side bias in
      females compared with males was observed but failed to reach significance. These
      data suggest that asymmetries in head orientation are present early in life in
      chimpanzees, and they may be correlated with functional asymmetries observed in
      adulthood.

PMID- 7576227
TI  - Inducible nitric oxide synthase and its product nitric oxide, a small molecule
      with complex biological activities.
AB  - More and more attention is paid to the radical nitric oxide which is now known to
      be part of the mammalian physiology and immune system. Nitric oxide is
      synthesized by one of the most complicated and fascinating enzyme families
      identified so far. Inducible nitric oxide synthesis after appropriate stimuli has
      regulatory, cytostatic and/or toxic consequences and may play an important role
      in the pathophysiology of several diseases.

PMID- 7576230
TI  - Visualization of tissue kallikrein in human breast carcinoma by two-dimensional
      western blotting and immunohistochemistry.
AB  - Tissue kallikrein is well known to liberate the vasoactive peptide kallidin from
      L-kininogen. Recently it was reported to activate matrix degrading
      metalloproteinases in vitro and to be present in gastric carcinoma cells. By
      immunohistochemistry we localized tissue kallikrein in the cytoplasm of ductal
      breast cancer cells. In addition, two-dimensional Western blotting was used to
      further characterize its biochemical properties. By this method immunoreactive
      tissue kallikrein was found to have a molecular mass of 25 kDa and an isoelectric
      point close to pH 6. Furthermore its presence in human milk could be
      demonstrated.

PMID- 7576228
TI  - Cytokine regulation of matrix metalloproteinase activity and its regulatory
      dysfunction in disease.
AB  - Matrix metalloproteinases (MMPs) represent a family of structurally and
      functionally related enzymes responsible for the proteolytic degradation of
      extracellular matrix (ECM) components such as basement membrane or interstitial
      stroma. MMPs are important participants of normal tissue remodeling. Due to their
      potential hazardous effects MMPs are highly regulated at different levels. At the
      transcriptional level, MMP expression is precisely controlled by various
      cytokines acting through positive or negative regulatory elements of its genes.
      Moreover, MMP activity is post-transcriptionally regulated by proteolytic
      activation of the latent proenzymes and by interaction with specific tissue
      inhibitors of metalloproteinases (TIMPs). Expression and secretion of both MMP
      activating enzymes and TIMPs are also influenced by cytokines. Dysregulation of
      MMP production and activation may cause altered extracellular proteolysis that is
      associated with a number of diseases such as rheumatoid arthritis and tumor
      metastasis. Thus, the molecular analysis of the regulatory mechanisms of gene
      expression and activity of MMPs and their inhibitors is essential for
      understanding the complex scenario of tissue remodeling and ECM degradation under
      both normal and pathological conditions.

PMID- 7576229
TI  - Cathepsins D, B and L in breast carcinoma and in transformed human breast
      epithelial cells (HBEC).
AB  - An increased expression of lysosomal enzymes, cathepsin (Cat) D, Cat B and Cat L,
      was observed in various human tumours and after in vitro cell transformation. To
      establish possible co-ordination in their expression, all three cathepsins were
      determined in human breast tumours and in transformed human breast epithelial
      cells (HBEC). In breast carcinoma (n = 120) all three cathepsins, determined
      immunochemically and by enzymatic activity, were increased compared to normal
      breast tissues. The activities, correlated with the corresponding protein masses
      for Cat D (r = 0.77, p < 0.01), but not for Cat B and Cat L. Significant increase
      in Cat B activity was observed in stage II compared to stage I tumours, and Cat L
      activity in stage III compared to stage II tumours, but no significant
      correlation of cathepsin protein with tumour stage (TNM) was established. No
      significant correlation between Cat D and the cysteine cathepsins B and L was
      observed. Similarly, Cat D, Cat B and Cat L levels did not correlate in the in
      vitro system, e.g. in the five transformed HBEC, such as evolved after
      dimethylbenz(a)anthracene treatment and c-Has-ras oncogene transfection of
      diploid MCF-10F cell line (Calaf et al., 1993). Transformed cells showed
      increased anchorage-independent growth and invasive capability (MCF-10 < MCF
      10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not related
      to cell invasiveness, while total cellular Cat B and Cat L increased 13 fold and
      4 fold, respectively, in the most invasive cell line, D3-1Tras compared to MCF
      10F.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576231
TI  - Purification and N-terminal amino-acid sequence analysis of rabbit neutrophil
      cathepsin G.
AB  - Cathepsin G was isolated from granules of rabbit bloodstream leukocytes and
      purified to apparent homogeneity by a multi-step procedure consisting of ammonium
      sulphate precipitation, affinity chromatography on elastin-Sepharose, and finally
      by ion-exchange chromatography on a CM-52 column. The molecular weight of the
      enzyme, as determined by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE), was 27,000. The first 24 N-terminal amino-acids were
      determined and showed 96%, 92% and 79% identity respectively to those of human,
      dog and rat cathepsin G. Despite the difference in the total amino-acid
      composition of cathepsin G between rabbit and other mammalian species, close
      similarities have been found in their substrate specificity and inhibition
      profile. The kcat/Km values of rabbit cathepsin G with Suc-Ala2-Pro-Phe-NA and
      Suc-Ala2-Pro-Leu-NA are quite similar to those reported for human cathepsin G
      under the same conditions. The inhibition profile of the isolated enzyme
      indicates that cathepsin G from rabbits, like that from other mammalians species
      belongs to the group of serine proteinases. Finally, like human cathepsin G,
      catalytically active rabbit enzyme is able to induce platelet aggregation.

PMID- 7576232
TI  - Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas
      and ovary molecular cloning, sequencing and tissue distribution.
AB  - A 1.6-kilobase full-length cDNA of a novel human cysteine protease has been
      isolated and sequenced. The nucleotide sequence encodes a polypeptide of 329
      amino acids composed of a 15-residue N-terminal signal peptide, a 99-residue
      propeptide, and a mature protein of 215 amino acids. The deduced amino acid
      sequence contains two potential N-glycosylation sites, one located in the
      proregion and one in the mature enzyme. Comparison of the amino acid sequence of
      cathepsin O2 with that of known human lysosomal cysteine proteases revealed a
      substantial degree of similarity to cathepsins L and S. Northern blot analysis
      indicates predominant levels of expression in osteoclastomas and ovary and
      therefore the enzyme was named cathepsin O2. The extremely high expression levels
      of human cathepsin O2 in osteoclastomas suggest a major role of this novel enzyme
      in bone remodelling and bone related diseases.

PMID- 7576233
TI  - Expression of full-length human procathepsin L cDNA in Escherichia coli and
      refolding of the expression product.
AB  - From human embrional lung fibroblasts mRNA was obtained and converted to cDNA.
      The procathepsin L coding region was amplified by PCR, inserted into pALTER and,
      after checking the nucleotide sequence, transferred into pET81F1+. Procathepsin L
      was expressed by induction of recombinant E. coli strain BL21[DE3](pLysS) with
      IPTG and was found to be deposited into inclusion bodies. These were isolated and
      solubilized in guanidinium hydrochloride. The soluble proteins were sulphonated
      and procathepsin L was obtained after gel filtration. Purified proenzyme was
      refolded by dialysis and autoactivated into a form of the expected size and
      enzymatic activity against a fluorogenic substrate.

PMID- 7576234
TI  - Induction of apoptosis in thymocytes: new evidence for an interaction of PKC and
      PKA pathways.
AB  - The second messenger cascades connected to PKC and PKA are involved in the
      induction of apoptosis. Here we study the interaction of those two second
      messenger pathways with respect to the induction of apoptosis by stimulation or
      inhibition. The stimulators used were phorbol dibutyrate for PKC and one of the
      cAMP agonists Sp-5,6 DCl-cBIMPS or Sp-cAMP for PKA. The inhibitors used were
      staurosporin for PKC and the cAMP antagonist Rp-cAMPS for PKA. We found a
      synergism between both second messenger systems with regard to the induction of
      apoptosis in thymus lymphocytes.

PMID- 7576235
TI  - Identification of an alanine aminopeptidase in human maternal serum as a membrane
      bound aminopeptidase N.
AB  - In addition to cystine aminopeptidase (oxytocinase) alanine aminopeptidase is
      present at high levels in the serum of pregnant women. In this study we compared
      the enzyme with membrane-bound aminopeptidase N purified from human placenta.
      Comparison of catalytic and immunological properties and N-terminal sequence
      analyses revealed that the enzymes were differentially processed derivatives of
      the same protein, and that the N-terminal 68 residues of aminopeptidase N were
      deleted in the alanine aminopeptidase. The deleted sequence contains a small
      cytoplasmic region, a hydrophobic transmembrane domain and a junctional domain.
      These results suggest that the enzyme may be released into the maternal
      circulation as a result of lacking these three domains.

PMID- 7576236
TI  - Lysosomal proteases cathepsins D, B, H, L and their inhibitors stefins A and B in
      head and neck cancer.
AB  - In cytosols of tumour and normal tissue of 53 patients suffering from head and
      neck carcinoma cathepsins D, B, H and L were measured using quantitative
      immunoreactive assays (ELISA). The values of cathepsins D, B and L were
      significantly higher in tumour tissue, whereas cathepsin H concentration was
      lower in tumour than in normal tissue. Median cathepsin D values were 27 pmol
      (tumour tissue) vs. 12 pmol (normal tissue) per mg of total protein, median
      cathepsin B values were 1.25 micrograms/mg (tumour tissue) vs. 0.23 micrograms/mg
      (normal tissue) and median cathepsin L values were 39.8 ng/mg (tumour tissue) vs.
      20.0 ng/mg (normal tissue). Median cathepsin H values were 1.05 micrograms/mg and
      2.20 micrograms/mg for tumour and normal tissue, respectively. Additionally,
      stefin A and stefin B were measured in tumour and normal tissue samples. In
      contrast to the cathepsins, the concentrations of these inhibitors of cysteine
      proteinases was not significantly different between tumour and normal samples.
      The concentrations of cathepsins D, B, H and L and stefins A and B measured in
      head and neck tumours, were independent of standard clinical and histological
      prognostic factors. Significant correlation of tumour tissue values was observed
      between cathepsins B and L and between both stefins.

PMID- 7576237
TI  - Quantification of intracellular cathepsin activities in human lung tumor cell
      lines by flow cytometry.
AB  - The cysteine proteases cathepsin B and cathepsin L are very likely involved in
      invasive processes of normal and malignant cells, they become relevant for a
      number of diseases and are possibly prognostic markers for the outcome of human
      lung cancer. Therefore, we have determined activities of these related enzymes in
      cells and in cell extracts of human lung carcinoma cell lines of different
      cathepsin composition by flow cytometry and by spectrophotometry, respectively.
      To this end we applied the synthetic dipeptidyl substrates benzoxycarbonyl
      arginyl-arginine- and benzoxycarbonyl-phenyl-arginine- coupled to 4-methoxy-beta
      naphthylamide, aminomethyl-coumarine or rhodamine R110. The apparent enzymatic
      activities were differentially defined by protease inhibitors, particularly E-64
      and CA-074. Independent of the dipeptidyl-composition more than 99 per cent of
      the apparent activity was due to cathepsin B when 4-methoxy-beta-naphthylamide or
      aminomethylcoumarine were the leaving groups. The 4-methoxy-beta-naphthylamide
      precipitate used for detection of cell associated activities revealed a wide
      spectrum of excitation to fluorescence thwarting the application of other
      possible fluorescent tags. Therefore, its application is restricted to
      uniparametric fluorescence investigations. Both dipeptidylgroups coupled to
      rhodamine R110 were promiscuous: only 25 to 30% of the apparent activity were due
      to cathepsin B; the predominant activity came from cathepsin L, irrespective
      whether intracellular or activities of cellular extracts were analyzed. However,
      rhodamine R110-coupled substrates open the way for multiparametric fluorescent
      analysis of cathepsins B and L containing cells if appropriate inhibitors for
      specification of the enzymatic activities are additionally applied. In very
      contrast to 4-methoxy-beta-naphthylamide, which causes irreparable damage to the
      cells, the rhodamine substrates permit studies with living cells and live cell
      sorting.

PMID- 7576238
TI  - In vitro fibril formation from alpha 1-antitrypsin-derived C-terminal peptides.
AB  - Fragments from various proteolytically degraded precursor proteins can form beta
      amyloid fibrils. We studied, by electron microscopy and quantitative Congo red
      binding, the ability of three synthetic peptides, corresponding to residues 359
      374 (C-36), 370-374 (C-5) and 375-394 (C-20) from the C-terminal part of alpha 1
      antitrypsin (AAT) to form beta-amyloid fibrils in vitro. The peptides C-36 and C
      5 had a pronounced tendency to form fibrils. C-20 lacked this property,
      suggesting that residues 359-375 and/or 370-374 are most critical for fibril
      formation. Native AAT added to peptide 125I-C-36 could bind and form complexes
      with the peptide, resulting in inhibition of amyloid fibril formation. Moreover,
      native AAT added to preformed fibrils induced disaggregation of fibrillar
      structures. The structural rearrangements of AAT that occurred during this
      'autointeraction' included polymerization of the serpin, and an increase of its
      thermal stability. Also, following interaction, an increase (20-40%) of AAT's
      antielastase activity was noted. The demonstration of an in vitro beta-amyloid
      fibril formation from the AAT derived C-terminal peptides C-36 and C-5 and its
      regulation by the intact AAT molecule may have important in vivo implications.

PMID- 7576240
TI  - Molecular cloning and characterization of the bovine and porcine outer dense
      fibers cDNA and organization of the bovine gene.
AB  - Outer dense fibers (ODF) or accessory fibers are filamentous structures of the
      sperm tail of many eumetozoan organisms endowed with internal fecundation. The
      bovine and porcine cDNA of an outer dense fiber protein was cloned, sequenced and
      compared to the previously characterized human and rat cDNA sequences. The coding
      sequences and the 5' and 3' untranslated regions of the ODF cDNAs are highly
      conserved. A comparison of the bovine, porcine, human and rat ODF protein
      sequences revealed that the protein displays a high degree of similarity, ranging
      from 87% to 98%. The ODF protein is rich in cysteine and contains the C.X.P.
      repeat at the C-terminal which is different in number among mammalian species.
      All the 27 cysteine residues in the ODF sequence except those in the C.X.P.
      repeat are conserved in the four species. We report here also the organization of
      the bovine ODF gene which is similar to that of human and rat. The transcription
      start site in the bovine ODF gene is localized 98 bp upstream of the translation
      start site. Alignment of the 5' flanking region of bovine ODF with the rat gene
      reveals that the first 130 nucleotides upstream of the transcription start site
      exhibit an overall sequence similarity of 83%. This conserved region contains a
      TATA-like box (TTTAAA) and binding sites for AFT/CREB and EGR-1 transcription
      factors.

PMID- 7576239
TI  - Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase
      1 in human dermal fibroblasts.
AB  - Recent reports have suggested that alpha-melanocyte stimulating hormone (alpha
      MSH) plays an important role in untraviolet (UV) irradiation mediated skin
      changes including pigmentation, inflammation and connective tissue damage. alpha
      MSH synthesis has been found to be induced in human keratinocytes following UV
      irradiation. In order to test the hypothesis whether UV induced alpha-MSH - via a
      paracrine loop - regulates the synthesis and the activity of collagenase/MMP-1,
      we studied the effects of alpha-MSH on the expression of MMP-1 and its tissue
      inhibitor of matrix metalloproteinases (TIMP-1). Confluent human dermal
      fibroblast cultures from foreskin biopsies of healthy human donors were treated
      with 10(-5)M, 10(-8)M and 10(-11)M alpha-MSH for 30 min. As determined by
      Northern blot analysis 10(-5)M and 10(-8)M alpha-MSH dose- and time-dependently
      induced steady state levels of MMP-1 mRNA up to 9-fold compared to untreated
      controls. TIMP-1 mRNA steady state levels were also slightly induced, however,
      the increased MMP-1/TIMP-1 ratio when normalized to beta-actin reflected an
      unbalanced synthesis. MMP-1 protein expression was studied with an
      immunofluorescence technique using a monoclonal antibody against MMP-1. After
      alpha-MSH treatment an increased number of fibroblasts revealed an intense
      perinuclear staining pattern compared to the less intense staining of control
      fibroblasts. The overall collagenolytic activity of supernatants from alpha-MSH
      treated fibroblasts was increased by 35%. Our data support the view that UV
      induced alpha-MSH - by the stimulation of collagenase/MMP-1 - may contribute to
      the loss of interstitial collagen related to cutaneous photoaging.

PMID- 7576242
TI  - Regulated expression of the retinoblastoma susceptibility gene in mammary
      carcinoma cells restores cyclin D1 expression and G1-phase control.
AB  - The product of the retinoblastoma susceptibility tumour suppressor gene, pRb, is
      a negative regulator of cell proliferation. In order to investigate the
      interaction between pRb and the cell cycle machinery in more detail, a functional
      Rb gene was reintroduced into the Rb-deficient human mammary carcinoma cell line
      Bt549. Since constitutive high level expression of Rb turned out to be difficult
      to maintain, the tetracycline-dependent gene expression system was used. A number
      of clones was generated which all showed low level expression in the noninduced
      state. Considerable induction rates were obtained. The low level of noninduced Rb
      expression was sufficient to induce the expression of cyclin D1 the level of
      which was not further increased by upregulation of Rb expression. Concomittantly,
      an increase in cell doubling time was observed due to retardation of the cell
      cycle in the G1-phase. The data suggest that limiting amounts of cyclin D1
      determine, at least partly, the extent of growth-repressing properties of pRb.
      The inducible system allows for maintenance of Rb-reconstituted cells at a low
      level of expression and for their use in the investigation of downstream
      functions of pRb.

PMID- 7576243
TI  - Felix Hoppe-Seyler (1825-1895) a pioneer of biochemistry and molecular biology.

PMID- 7576241
TI  - Amino acid sequence of alpha- and beta-polypeptide chains of turkey (Meleagris
      gallopavo) hemoglobin.
AB  - Two hemoglobin components are recognized in erythrocytes of the adult turkey
      (Meleagris gallopavo). We determined the amino acid sequences of turkey alpha A-,
      alpha D- and beta-globin from intact globin chains and chemical cleavage
      fragments. The sequences are highly similar to the hemoglobin of the Phasianidae,
      chicken, Japanese quail and pheasant. Turkey and pheasant beta-globin are
      identical. The amino acid sequence of turkey alpha A-globin differs by only one
      residue from chicken alpha A-globin. Phylogeny trees from alpha A-, alpha D- and
      beta-globin were constructed by the neighbor-joining method. Although the trees
      generated from alpha A- and beta-globin were similar, that from turkey alpha D
      globin differed.

PMID- 7576244
TI  - Hoppe-Seyler, Stokes and haemoglobin.

PMID- 7576245
TI  - Lysyl-tRNA synthetase.
AB  - Lysyl-tRNA synthetase catalyses the formation of lysyl-transfer RNA, Lys
      tRNA(Lys), which then is ready to insert lysine into proteins. Lysine is
      important for proteins since it is one of only two proteinogenic amino acids
      carrying an alkaline functional group. Seven genes of lysyl-tRNA synthetases have
      been localized in five organisms, and the nucleotide and the amino acid sequences
      have been established. The lysyl-tRNA synthetase molecules are of average chain
      lengths among the aminoacyl-tRNA synthetases, which range from about 300 to 1100
      amino acids. Lysyl-tRNA synthetases act as dimers; in eukaryotes they can be
      localized in multienzyme complexes and can contain carbohydrates or lipids.
      Lysine tRNA is recognized by lysyl-tRNA synthetase via standard identity
      elements, namely anticodon region and acceptor stem. The aminoacylation follows
      the standard two-step mechanism. However the accuracy of selecting lysine against
      the other amino acids is less than average. The first threedimensional structure
      of a lysyl-tRNA synthetase worked out very recently, using the enzyme from the
      Escherichia coli lysU gene which binds one molecule of lysine, is similar to
      those of other class II synthetases. However, none of the reaction steps
      catalyzed by the enzyme is clarified to atomic resolution. Thus surprising
      findings might be possible. Lysyl-tRNA synthetase and its precursors as well as
      its substrates and products are targets and starting points of many regulation
      circuits, e.g. in multienzyme complex formation and function, dinucleoside
      polyphosphate synthesis, heat shock regulation, activation or deactivation by
      phosphorylation/dephosphorylation, inhibition by amino acid analogs, and
      generation of antibodies against lysyl-tRNA synthetase. None of these pathways is
      clarified completely.

PMID- 7576247
TI  - Alterations in the visual cortex receptor pattern by operant conditioning in a
      reward paradigm.
AB  - The aim of the study was to investigate the impact of operant conditioning on the
      receptor pattern in the visual cortex of calves. A reward paradigm was used to
      induce conditioned preference for colours. Binding sites in visual cortex
      specimens from conditioned and naive animals were assayed in vitro on cellular
      basis after dissociation of the tissue by collagenase, incubation with
      fluorescent ligands and flow-cytometry for fluorescence analysis. The cellular
      counts were subdivided according to sedimentation at 200 g as well as via the
      flow-cytometrical histogram by size and granularity. Binding sites of dopamine D1
      and D2 receptor subtypes, glucocorticoids, opioids, casein as well as glycine and
      N-methyl-D-aspartic acid (NMDA) were detected by fluorescent molecular probes. In
      displacing naloxone fluorescein from NMDA- and mu-opioid receptors NMDA and meth
      enkephalin were used. Comparisons between portions of fluorescent cellular counts
      from visual cortex tissue of conditioned and naive animals revealed a small
      increase (1.2-fold, P < 0.05) in opioid receptors of large and high granulated
      counts, bearing > 80% D1 receptors, and a decrease (0.70-fold, P < 0.05) in less
      granulated counts with variable portion of D1 receptors. Conditioning resulted in
      higher and lower displacing rates by meth-enkephalin and NMDA, resp., and in a
      reduce in counts with dopamine D1 (0.8-fold, P < 0.05), glycine and
      glucocorticoid binding sites (0.6-fold in both cases, P < 0.01). A tendency of
      elevated phagocyte marker expression occurred in high granulated counts. The data
      suggest that conditioning is accompanied with significant and in part marked
      change in binding sites studied. Induction of scavenger activity may parallel
      this process. As cellular portion with glycine and glucocorticoid receptors were
      most markedly altered by conditioning, the neurochemical needs of the used
      paradigm seem to focus to motility-related functions.

PMID- 7576246
TI  - Characterization of the epitope recognized by a monoclonal antibody directed
      against the largest subunit of Drosophila RNA polymerase II.
AB  - The epitope recognized by monoclonal antibody MAb215 generated previously against
      Drosophila melanogaster RNA polymerase II was mapped to amino acid residues 806
      820 of the largest, 215 kDa, subunit located in a region conserved within the
      largest subunits of pro- and eukaryotic RNA polymerases. The affinities of MAb215
      and of a recombinant single-chain Fv fragment (scFv215) were determined for
      binding to the enzyme as well as the fusion protein and synthetic peptides used
      for epitope mapping. In addition, amino acid residues of the epitope important
      for binding to MAb215 were identified using peptides carrying single amino acid
      substitutions. The epitope is not involved in the polymerization reaction or the
      DNA unwinding process since no inhibitory effects of the monoclonal antibody were
      observed in nonspecific in vitro transcription using denatured calf thymus DNA or
      double stranded oligo dC-tailed T7 DNA as template. In contrast, MAb215 inhibits
      accurate in vitro transcription from the Kruppel gene promoter and from the
      adenovirus-2 major late promoter. Preincubation of template DNA with the nuclear
      extract had no effects on inhibition supporting the notion that the epitope does
      not participate directly in the formation of preinitiation complexes. The same
      inhibitory effects were observed using scFv215. The results provide further
      evidence that recombinant antibody fragments produced in Escherichia coli possess
      the same specificity and similar affinity as their parental antibodies and
      demonstrate that scFv fragments are useful tools for analysis of transcriptional
      processes.

PMID- 7576248
TI  - Generation and activity of the ternary gelatinase B/TIMP-1/LMW-stromelysin-1
      complex.
AB  - Incubation of progelatinase B, isolated from human polymorphonuclear leukocytes,
      with TIMP-1 leads to the formation of the progelatinase B/TIMP-1 complex. This
      complex behaves like a Janus in a similar manner as we previously described for
      the progelatinase A/TIMP-2 complex. It shows the properties of TIMP-1 and is a
      better inhibitor for gelatinase A than for gelatinase B. Treatment with trypsin
      leads to activation of the binary complex. The activity, however, amounts only to
      slightly more than 10% of the activity of free gelatinase B, not complexed with
      TIMP-1. When the progelatinase B/TIMP-1 complex inhibits an active matrix
      metalloproteinase, a ternary complex is generated that after activation displays
      a distinct higher proteolytic activity than the active binary complex. The active
      binary complex cannot be transformed into the active ternary complex.

PMID- 7576249
TI  - n-alkylglucosides serve as acceptors for galactosyltransferases from rat liver
      Golgi vesicles.
AB  - n-Alkyl alpha- and beta-D-glucopyranosides with different alkyl chain lengths
      (Glc-O-CxH2x+1) and n-octyl beta-D-thioglucopyranoside (Glc-S-C8H17) were
      synthesized, and used as acceptors for galactosyltransferases from rat liver
      Golgi vesicles. Only the beta-anomers were galactosylated and at constant
      substrate concentration, the reaction rates reached a maximum for medium alkyl
      chain lengths (C6, C8 and C10). Apparent Km and Vmax values decreased with
      increasing alkyl chain length. The reaction products were identified as n-alkyl
      beta-lactosides by means of thin layer chromatography, fast atom bombardment mass
      spectrometry and 1H-NMR spectroscopy. Competition experiments showed that UDP
      Gal: N-acetylglucosamine beta 1-4-galactosyltransferase (EC 2.4.1.38) and not UDP
      Gal: glucosylceramide beta 1-4-galactosyltransferase (lactosylceramide synthase,
      GalT-2) was responsible for the galactosylation of alkyl glucosides.

PMID- 7576250
TI  - Molecular cloning and identification of a novel porcine cathelin-like
      antibacterial peptide precursor.
AB  - A novel clone (C6) encoding the precursor of a 79-residue proline/arginine-rich
      antibacterial peptide prophenin was isolated from a porcine bone marrow cDNA
      library. Its deduced N-terminal propart shows 84% identity with cathelin.
      Additionally, two cathelin isoforms were isolated from peripheral porcine blood
      and their N-termini sequenced. The sequence of one isoform corresponds to the
      cathelin sequence, whereas that of the other protein is identical to the
      propeptide of C6 clone. Western blot analysis of total proteins from porcine and
      human bone marrow using polyclonal antibodies against cathelin revealed the
      presence of immunochemically related high molecular mass proteins of about 30 kDa
      in both samples, whereas low molecular mass proteins of approximately 12 kDa,
      corresponding to isolated cathelin, were not detected in human bone marrow.

PMID- 7576251
TI  - Rat and human glutamate transporter GLAST1 stable heterologous expression,
      biochemical and functional characterization.
AB  - Human embryonic kidney cell lines (HEK293) which express heterologously and
      permanently the human and rat GLAST1 (high affinity, Na(+)-dependent, CNS
      specific L-glutamate transporter) have been established by the transfer of the
      two minigenes under the control of the cytomegalovirus promoter by
      electroporation. The transfected HEKh GLAST1 (human) and HEKrGLAST1 (rat) cell
      lines strongly express the glutamate uptake system which exhibits all biochemical
      and electrophysiological properties determined so far in the transiently
      expressing Xenopus oocyte system except the K+ dependence. These cell lines are a
      valuable tool for further biochemical, physiological, and pharmacological studies
      on this uptake system of the most important excitatory neurotransmitter.

PMID- 7576252
TI  - Posttranslational mitochondrial protein import in a homologous yeast in vitro
      system.
AB  - Posttranslational import of preproteins into mitochondria has been reported to be
      inefficient in a homologous yeast in vitro system, suggesting a requirement for
      coupling of protein synthesis and import. We have characterized a homologous
      yeast in vitro system which allows posttranslational mitochondrial import of
      preproteins. The efficiency is comparable to that of the heterologous system with
      rabbit reticulocyte lysate and isolated yeast mitochondria. Import in the
      homologous system depends on mitochondrial surface receptors, a membrane
      potential and the matrix heat shock protein Hsp70. Import is not blocked by the
      protein synthesis inhibitor cycloheximide, but is impaired by induction of stable
      folding in preproteins. Our studies demonstrate a posttranslational translocation
      mechanism in the homologous system, strongly supporting the validity of
      conclusions drawn from the widely used heterologous import system.

PMID- 7576254
TI  - Effect of saponin from Quillaja saponaria (molina) on antibody, tumour necrosis
      factor and interferon-gamma production.
AB  - Saponin has been described to contain adjuvant activity in vaccination protocols,
      in protection against disease, and on humoral immune response. In this paper we
      describe the effect of a pure saponin from Quillaja saponaria (molina) on the
      immune response elicited in mice by two antigens, BSA and Crotalus durissus
      terrificus (South American rattlesnake) venom. Antibody production as measured by
      ELISA shows that saponin was able to increase antibody synthesis to both
      antigens. Moreover, mice immunized with verom plus saponin were completely
      protected against the lethal effects of the venom. The effect of saponin was also
      evaluated for cytokine production. Tumour necrosis factor activity about 2.9
      times higher than in control mice was detectable in sera from animals immunized
      with saponin. Interferon-gamma was produced only when BSA and saponin were
      injected together into the mice.

PMID- 7576253
TI  - Derivatives of colchicine preferentially taken up by the liver: an approach to
      the treatment of liver fibrosis.
AB  - The distribution in the mouse of colchicine and of two colchicine derivatives,
      namely formylcolchicine/formylated serum albumin (FC/FTSA) and
      formylcolchicine/lactosaminated serum albumin (FC/LASA), was studied. The
      presence of radioactivity after the intravenous injection of labelled colchicine
      or of its derivatives was determined in liver, small intestine, kidney and blood.
      The radioactivity of the derivatives was better retained than that of colchicine.
      The derivatives accumulated in the liver to a much greater extent than
      colchicine, but were scarcely present in the gut. Tropism towards the liver might
      be important for the use of FC/LASA and FC/FTSA to control liver fibrosis.

PMID- 7576255
TI  - Transforming growth factors beta: conformational stability and features of the
      denaturation of recombinant human transforming growth factors beta 2 and beta 3.
AB  - Transforming growth factors beta (TGF-beta) are cytokines with multiple
      biological activities. Their development as biopharmaceutical drugs targets the
      control of complex physiological processes such as osteogenesis and epithelial
      cell differentiation. We report here the first characterization of the
      recombinant human (rh) TGF-beta 2 and rhTGF-beta 3 isoforms in terms of their
      conformational stability and structural transitions induced by a chaotrope or
      temperature. The transitions detected by CD spectroscopy suggested that thermal
      denaturation of both TGF-beta isoforms apparently fitted a simple two-state
      (N<==>D) model. However, the ratios of calorimetric to van't Hoff enthalpies,
      significantly different from unity, indicated that these molecules most probably
      consist of independently denaturing subdomains. The complex transitions induced
      by guanidine hydrochloride, at pH 1.8 or 8.0, also suggested intermediately
      denatured structures. Thermodynamic stabilities under pH conditions useful for
      bioprocessing were derived from spectroscopic and calorimetric measurements.
      Treatment of thermal denaturation data by van't Hoff analysis yielded, for the
      beta 2 and beta 3 isoforms respectively, apparent delta G(25 degrees C, pH 1.8)
      of 20.4/17.2 kJ/mol and 17.5/18.6 kJ/mol (near-UV CD/far-UV CD data) in 20 mM
      hydrochloric acid, and apparent delta G (25 degrees C, pH 3.0) of 35.1 and 33.5
      kJ/mol in 0.25 M acetic acid (calorimetric data). Neither low-pH-induced
      denatured states nor soluble aggregates were detected in both acidic solvents.
      The spectroscopic and thermodynamic data should be useful for assessing the
      homogeneity and proper folding of these recombinant molecules.

PMID- 7576257
TI  - Radiolabelling of human haemoglobin using the 125I-Bolton-Hunter reagent is
      superior to oxidative iodination for conservation of the native structure of the
      labelled protein.
AB  - Both disruption of the native protein structure and oxidation of iron in the
      haem/iron(II)-proto-porphyrin-IX residues were observed using the Iodo-gen
      (1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycouril) method in 125I-labelling
      of haemoglobin. The reactions taking place affect the native structure of
      haemoglobin and result in a more acidic molecule. The detrimental effects were
      unaffected by the presence of iodine. Electrophoretic studies demonstrate that
      125I-labelling of haemoglobin using the Bolton-Hunter reagent is the method of
      choice in order to preserve the native protein.

PMID- 7576256
TI  - Proteolysis of fusion proteins: stabilization and destabilization of
      staphylococcal protein A and Escherichia coli beta-galactosidase.
AB  - The product yield of staphylococcal Protein A reached only 1.8% of the cell dry
      weight, while the corresponding value was 14% for a fusion protein composed of
      Protein A and Escherichia coli beta-galactosidase [1], when produced in the same
      E. coli host strain, with the same promoter and under identical process
      conditions. Measurement of the stability of Protein A in vivo showed that it was
      quickly degraded in the cell with a half-life of 30 min when the protein was
      expressed alone, but after fusion to beta-galactosidase, the Protein A part
      became considerably stabilized. In spite of the fast intracellular proteolysis of
      Protein A, few degradation products could be identified on Coomassie Brilliant
      Blue-stained SDS/PAGE gels after IgG purification, indicating an even faster
      degradation of the Protein A fragments. Such degradation products, however,
      accumulated during incubation of the disintegrated cells. Intracellular
      degradation intermediates could be demonstrated with the more sensitive Western
      blot technique. This technique also revealed that a slow degradation took place
      not only in the Protein A moiety of the fusion protein, but also in the beta
      galactosidase moiety. A control with native beta-galactosidase also showed a weak
      in vivo proteolysis of this molecule, but it was more stable in free form than in
      the fused form. This means that the proteolytically very sensitive Protein A was
      stabilized by fusion with beta-galactosidase, but the originally rather stable
      beta-galactosidase became slightly more susceptible to proteolysis after the
      fusion.

PMID- 7576260
TI  - The influence of enzyme concentration on the encapsulation of glutamate
      dehydrogenase and alcohol dehydrogenase in red blood cells.
AB  - Glutamate dehydrogenase (GDH) and alcohol dehydrogenase (ADH) have been
      encapsulated in sheep and human red blood cells (RBCs) by a hypotonic
      dialysis/isotonic resealing procedure. At a fixed enzyme level in the dialysis
      bag (100 units/ml of RBCs), a significant encapsulation yield was observed for
      ADH, both in human (17.2%) and sheep (47.9%) RBCs, whereas a very low entrapment
      of GDH was achieved (1-3%) in either species. Carrier cell recovery was 61-65% in
      humans and 30-34% in sheep. Because of the aggregation of GDH to large polymers
      at protein levels above 1 mg/ml, the yield of encapsulation and the specific
      activity in human carrier RBCs were compared at different enzyme concentrations.
      While entrapment was not affected by differences in ADH up to 13,000 units/ml of
      RBCs (38 mg/ml), the yield of GDH encapsulation significantly decreased as the
      enzyme level increased up to 750 units/ml of RBCs (15 mg/ml), thus demonstrating
      the importance of protein concentration in the encapsulation process for those
      enzymes that tend to aggregate.

PMID- 7576258
TI  - Enzyme thermostabilization by bovine serum albumin and other proteins: evidence
      for hydrophobic interactions.
AB  - BSA stabilizes Streptococcus thermophilus beta-galactosidase against thermal
      inactivation and binds to the active enzyme subunits formed on heating. The
      mechanism of interaction and stabilization, however, is unknown, and it was
      investigated using different proteins. The results show that several proteins
      increased the enzyme half-life (t 1/2) at 64 degrees C in the presence of the
      substrate lactose. The best stabilizers were BSA (9-fold) and casein (6-fold).
      There was a significant correlation between enzyme half-life (t 1/2) and surface
      hydrophobicity of the proteins (So), of the form t 1/2 varies; is directly
      proportional to S0.5o. The surface hydrophobicity of the enzyme increased upon
      heating, while that of BSA declined. Heating enzyme and BSA together caused a net
      loss in surface hydrophobicity, indicating hydrophobic interactions, but there
      was no change in the absence of heating. Stabilization of the enzyme by BSA was
      markedly affected by chaotropic and kosmotropic salts. Stabilization was
      increased by 1 M Na2SO4 and reduced by 1 M NaBr; 1 M NaCl had little effect. None
      of the three salts increased the stability of the enzyme itself, indicating that
      the effect was on the enzyme-protein interaction. The results indicate that BSA
      stabilized the enzyme by hydrophobic interactions with the heated enzyme and that
      surface hydrophobicity is a major determinant of the extent of stabilization by a
      protein.

PMID- 7576259
TI  - Improved isolation, stability and substrate specificity of cucumisin, a plant
      serine endopeptidase.
AB  - Cucumisin (EC 3.4.21.25), a serine endopeptidase, was isolated by a simple
      purification procedure from the prince melon (Cucumis melo ssp. melo, cv. 'Prince
      Melon'). The enzyme is stable over a wide pH range (4-11) and to heat, 80% of its
      initial activity remaining even at pH 11.1 and at 60 degrees C for 20 min. The
      enzyme was inactive at 72 degrees C and pH 8.0, but 38% of the activity remained
      in the presence of 10% (w/v) glycerol. Caseinolysis by cucumisin indicated full
      activity in 8 M urea at pH 9.1 and 50 degrees C. Cucumisin was inactivated by
      treatment with trypsin at 37 degrees C for 24 h, but was not affected by alpha
      chymotrypsin. The synthetic substrates benzyloxycarbonyltyrosine nitrophenyl
      ester (Z-Tyr-ONp) and benzoyltyrosine ethyl ester (Bz-Tyr-OEt) were cleaved, but
      Z-Lys-ONp and tosylarginine methyl ester (Tos-Arg-OMe) were not cleaved by
      cucumisin. Oxidized insulin B-chain was hydrolysed by cucumisin at 37 degrees C
      for 24 h, 21 cleavage sites being detected. Cucumisin could not cleave the C
      termini of all the valine residues in the oxidized insulin B-chain molecule.

PMID- 7576261
TI  - Effect of aerobic pretreatment with Aspergillus terreus on the anaerobic
      digestion of olive-mill wastewater.
AB  - A kinetic study was carried out on the anaerobic digestion of olive-mill
      wastewater (OMW) and OMW that was previously fermented with Aspergillus terreus.
      The bioreactors used were batch fed and contained saponite as support for the
      mediating bacteria. The anaerobic digestion process followed first-order
      kinetics, from which the kinetic constant A was calculated using a non-linear
      regression. This kinetic parameter was influenced by the pretreatment carried
      out, and was 3.7 times higher for pretreated OMW than for untreated OMW. The
      anaerobic processing of pretreated OMW seemingly involved no inhibition phenomena
      as the biotoxicity and the total phenolic compound content (analysed by HPLC)
      were reduced by 71.2% and 77.9% respectively as a result of the pretreatment.
      Finally, the yield coefficient of methane production was 0.345 litres of methane
      (at standard temperature and pressure)/g of chemical oxygen demand, that is, 23%
      higher than that provided by untreated wastewater.

PMID- 7576264
TI  - ACE inhibitors and impotence: a case series from the Spanish drug monitoring
      system.

PMID- 7576263
TI  - Sensitisation to corticosteroids. Consequences for anti-inflammatory therapy.
AB  - The frequency with which sensitisation to corticosteroids occurs is under
      recognised, and depends on factors such as the type and amount of corticosteroid
      used, the awareness of the need to test for corticosteroid sensitivity and the
      methods used to do so. Topically applied corticosteroids, in particular, but also
      inhalation and systemic corticosteroids may cause allergic reactions. The
      clinical picture as well as the patch test reactions can be deceptive. Moreover,
      concomitant and cross-reactions are common.

PMID- 7576262
TI  - Macrolide antibacterials. Drug interactions of clinical significance.
AB  - Macrolide antibiotics can interact adversely with commonly used drugs, usually by
      altering metabolism due to complex formation and inhibition of cytochrome P-450
      IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug
      interactions with macrolides can result from their antibiotic effect on
      microorganisms of the enteric flora, and through enhanced gastric emptying due to
      a motilin-like effect. Macrolides may be classified into 3 different groups
      according to their affinity for CYP3A4, and thus their propensity to cause
      pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs
      decrease drug metabolism and may produce drug interactions (group 1). Others,
      including clarithromycin, flurithromycin, midecamycin, midecamycin acetate
      (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause
      interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do
      not inactivate CYP3A4 and do not engender these adverse effects. Drug
      interactions with carbamazepine, cyclosporin, terfenadine, astemizole and
      theophylline represent the most frequently encountered interactions with
      macrolide antibiotics. If the combination of a macrolide and one of these
      compounds cannot be avoided, serum concentrations of concurrently administered
      drugs should be monitored and patients observed for signs of toxicity. Rare
      interactions and those of dubious clinical importance are those with alfentanil
      and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine,
      clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids,
      felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin,
      methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin
      (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and
      zidovudine.

PMID- 7576266
TI  - How safe is the readministration of streptokinase?
AB  - Streptokinase is an antigenic thrombolytic agent used for the treatment of acute
      myocardial infarction. It reduces mortality as effectively as the nonantigenic
      alteplase in most infarct patients while having the advantage of being much less
      expensive. This cost implication is important since myocardial reinfarction is
      common, with fibrinolytic therapy indicated in many patients with reinfarction.
      Following streptokinase, antistreptokinase antibodies and neutralisation titres
      can rise to significant levels from 4 days after the initial dose. These
      antibodies can presist for at least 4 years in up to 50% of patients. It is
      possible that these antibodies may cause allergic reactions or neutralisation of
      a further dose of streptokinase, rendering it ineffective for the treatment of
      myocardial reinfarction. To date, 2 small studies of patients without previous
      streptokinase exposure suggest that higher antibody titres are associated with a
      lower rate of coronary reperfusion, while a further study suggests that high
      titres are associated with hypersensitivity reactions. At present the
      readministration of streptokinase cannot be recommended from 4 days after a first
      dose. Further larger studies are needed to assess the effect of high
      neutralisation titres on coronary reperfusion.

PMID- 7576265
TI  - Long-term aspirin in the prevention of cardiovascular disorders. Recent
      developments and variations on a theme.

PMID- 7576269
TI  - Skull base surgery.

PMID- 7576270
TI  - Stereotactic multiple arc radiotherapy. I. Vascular malformations of the brain:
      an analysis of the first 108 patients.
AB  - Between March 1989 and December 1993, 101 patients with inoperable arteriovenous
      malformations (AVMs) and seven patients with inoperable angiographically occult
      malformations (AOVMs) have been treated with stereotactic multiple arc
      radiotherapy (SMART). All patients (excluding one patient with a brain stem AOVM)
      were treated with a uniform dose of 1750 cGy prescribed to the 90% isodose. Fifty
      two patients with AVMs have had follow-up angiographic studies performed 11-42
      months after SMART. The complete angiographic obliteration rates were 75-77% for
      AVMs < 10 cm3 and 40-75% for AVMs > 10 cm3, when studied 18-30 months after
      SMART. Four patients re-bled prior to complete obliteration representing an
      actuarial 2-year incidence of re-bleeding of 5.1%. Seven patients developed a new
      neurological deficit after SMART after a median latent interval of 17 months
      (range 6-32). The actuarial 2-year incidence of neurological complications was
      1.8% for lesions < 10 cm3. The actuarial 2-year incidence of neurological
      complications was 16% for lesions > 10 cm3 (10.5% for persisting deficit). Of
      seven patients with AOVM six have shown a reduction in size and degree of
      contrast enhancement, but in no patient has there been complete resolution shown
      by CT. Five patients with AOVMs developed symptomatic neurological deterioration
      at a median of 6 months after SMART (range 5-9). When viewed in the context of
      the natural history of conservatively managed inoperable AVMs, this series has
      demonstrated that our highly specialized irradiation technique is a safe and
      effective treatment for many patients.

PMID- 7576271
TI  - Hyperprolactinaemia in patients with pituitary adenomas. The pituitary stalk
      compression syndrome.
AB  - Hyperprolactinaemia, unexplained by prolactin-production of the tumour is
      occasionally found in patients with pituitary tumours. This secondary
      hyperprolactinaemia has been ascribed to a mass effect of the tumour upon the
      pituitary stalk, obstructing the normal inhibitory hypothalamic influence on the
      prolactin producing cells. In this study the adenoma volume, amount of
      suprasellar enlargement of the tumour and the intrasellar pressure were measured
      in 42 patients operated upon consecutively for pituitary tumours. Secondary
      hyperprolactinaemia was found in six (14%). There was no difference as regards
      adenoma volume, amount of suprasellar extension or intrasellar pressure between
      the group of patients with elevated p-prolactin versus the group with normal p
      prolactin. We conclude that mechanisms other than pituitary stalk compression
      must be considered as the cause of secondary hyperprolactinaemia.

PMID- 7576267
TI  - Health risks of herbal remedies.
AB  - Herbal remedies can result in indirect health risks when they delay or replace a
      more effective form of conventional treatment or when they compromise the
      efficacy of conventional medicines. Herbal remedies can also be associated with
      direct health risks. Long-standing traditional experience may tell much about
      striking and predictable symptoms of acute toxicity but it is a less reliable
      tool for the detection of reactions which are inconspicuous, develop gradually or
      have a prolonged latency period, or which occur uncommonly. Another reason why
      safety claims cannot always be based on traditional empiricism is that not all
      herbal remedies are firmly rooted in traditional medicine. The risk of a herbal
      remedy producing an adverse reaction depends not only on the remedy and its
      dosage but also on consumer-related parameters, such as age, genetics,
      concomitant diseases and concurrent use of other drugs. Another important
      determinant of the toxicity of herbal remedies is their quality. What is already
      known about the risks of herbal remedies must be systematically collected,
      disseminated and acted upon. What is yet unknown must be found out by herbal
      postmarketing surveillance and experimental research.

PMID- 7576272
TI  - Surgical management of spinal cord cavernoma.
AB  - Three cases of surgically verified intramedullary cavernous angioma (cavernoma)
      of the spinal cord are reported. Intramedullary cavernomas of the cord are quite
      uncommon and account for between 3 and 12% of all vascular lesions of the spinal
      cord. Little is known of their natural history, although their tendency to
      produce haemorrhage and episodic symptomatic worsening is recognized. Our series
      includes one male and two females whose ages ranged between 31 and 67 years. The
      most common presenting symptom was pain, which in all cases preceded weakness. In
      two of our cases, the typical progression of sudden paroxysmal worsening of
      symptoms accompanied by pain was noted. This was thought to be related to
      bleeding in the lesion. In this series, an average of 8 years had elapsed after
      the onset of symptoms before the patients came to surgery. Standard microsurgical
      technique facilitated removal of the lesions, following which all patients
      regained preoperative function.

PMID- 7576268
TI  - The serotonin syndrome. Implicated drugs, pathophysiology and management.
AB  - The serotonin syndrome has increasingly been recognised in patients who have
      received combined serotonergic drugs. This syndrome is characterised by a
      constellation of symptoms (confusion, fever, shivering, diaphoresis, ataxia,
      hyperelflexia, myoclonus or diarrhoea) in the setting of the recent addition of a
      serotonergic agent. The most common drug combinations causing the serotonin
      syndrome are monoamine oxidase inhibitors (MAOIs) and serotonin selective
      reuptake inhibitors (SSRIs), MAOIs and tricyclic antidepressants, MAOIs and
      tryptophan, and MAOIs and pethidine (meperidine). This syndrome is caused by
      excess serotonin (5-hydroxytryptamine; 5-HT) availability in the CNS at the 5
      HT1A-receptor. There may also be some interaction with dopamine and 5-HT2
      receptors. This syndrome probably has a low incidence, even among patients taking
      these drug combinations, and there is likely to be some other as yet unidentified
      inciting factor causing some patients to develop a full serotonin syndrome.
      Because fatalities and severe complications have accompanied the serotonin
      syndrome, the previously described drug combinations should be used cautiously or
      not at all. The serotonin syndrome is usually mild and, if managed with drug
      withdrawal and supportive therapy, generally improves within hours. Patients who
      develop hyperthermia should be treated aggressively with external cooling and
      paralysis. Methysergide and cyproheptadine appear to be useful adjuncts in
      treating the serotonin syndrome.

PMID- 7576275
TI  - Outcome after repeat lumbar microdiscectomy.
AB  - One of the standard treatments for herniation of lumbosacral disc material has
      become the microdiscectomy. Although multiple studies have assessed the outcome
      of microdiscectomy, only a few studies have evaluated the outcome of those
      patients who have undergone a second microdiscectomy at the same location as the
      original one. The purpose of this study was to review 55 patients who, over a 4
      year period, underwent a second microdiscectomy at the same location as their
      original operation and to evaluate those factors associated with improved
      outcomes. The results showed the overall outcome to include 86% with complete or
      partial relief of all pain symptoms; 88% with complete or partial relief of
      sciatica; 85% with complete or partial relief of back pain; 100% returning to
      work in an average of 7 weeks; and 89% were glad they had the second operation.
      Those factors without predictive value included age, sex, weight, height, level
      of operation, side of operation, surgeon at the first or second operation (e.g.
      consultant or junior staff), length of the first operation ( < or = 60 min or >
      60 min) and duration of symptoms before the first operation. The key features
      centred on preoperative job status, the interval between recurrence of symptoms
      and the second operation, and the duration of the second operation ( < or = 90
      min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576274
TI  - The preoperative assessment of stroke risk in lesions involving the internal
      carotid artery.
AB  - Patients with vascular or tumourous lesions involving the internal carotid artery
      are at risk of damage or occlusion of this vessel during surgical or endovascular
      procedures. To assess the stroke risk transcranial Doppler aided carotid
      compression tests were performed in 82 patients. Based on changes of blood flow
      velocity (BFV), pulsatility index, systolic/diastolic ratio and length of
      transient hyperaemic response three groups could be differentiated. Patients in
      group A (31%) showed only a slight reaction of BFV and were at minimal risk in
      case of carotid occlusion. Patients in group B (52%) underwent a distinct
      decrease of Doppler readings with partial improvement and were considered to have
      moderate to high stroke risk. In group C patients (17%) trial occlusion caused a
      dramatic reduction of BFV with no recovery (p < 0.01), which denotes a very high
      stroke risk. Transcranial Doppler aided carotid occlusion manoeuvres provide
      useful information on cerebrovascular collateral capacity and prognosis of stroke
      risk.

PMID- 7576273
TI  - Quality of life and cognitive deficits after subarachnoid haemorrhage.
AB  - In a retrospective study of 58 patients after subarachnoid haemorrhage (SAH) with
      a late result either good (GOS = I) or fair (GOS = II), patients were examined 1
      5 years after the acute event for their quality of life including a
      neuropsychological examination. Cognitive deficits were found in visual short
      term memory (46%) and in the three parameters of a reaction-time task ranging
      from 31 to 65%. Further deficits were found in verbal long-term memory (28%),
      concentration (5-13%) and language (11%). The quality of life was reduced in the
      SAH patients according to a self-rating scale in motivation (50%), interests
      (47%), mental capacity (47%), free-time activities (52%), social relationships
      (39%), concentration (70%), fine motor co-ordination (25%) and sleep (47%). A
      further 77% of the patients reported more frequent headaches since their SAH.
      Depression was found in 30% of the SAH patients. Life-satisfaction was
      significantly reduced in 37%, whereas 48% of the SAH patients suffered from
      increased emotional lability and in 41% motivation was significantly reduced.
      Negative job consequences like loss of job or demotion were reported by 16% of
      the patients investigated and an additional 15% had been retired.

PMID- 7576277
TI  - Stimulation of the globus pallidus in Parkinson's disease.
AB  - In 62 patients undergoing posteroventral pallidotomy (PVP) for the treatment of
      Parkinson's disease, we have demonstrated significant (p < 0.01) elimination of
      akinetic features and other symptoms during intraoperative stimulation trials in
      areas anterior to the PVP target (n = 30). Stimulation in anterior pallidal
      regions frequently resulted in an immediate reversal of akinetic states despite
      enforced abstinence of medications. The beneficial effects were achieved with as
      little as 0.25 V at 100 Hz. Stimulation at the PVP target site (n = 32) resulted
      in insignificant changes (p > 0.05).

PMID- 7576276
TI  - Magnetic resonance imaging: a cost-effective first line investigation in the
      detection of vestibular schwannomas.
AB  - Magnetic resonance imaging (MRI) is currently the 'gold-standard' investigation
      in patients with a unilateral sensorineural hearing loss. The procedure, however,
      is expensive and of limited availability. Instead, such patients often undergo a
      series of audiovestibular tests and computed tomography in an attempt to exclude
      or diagnose a vestibular schwannoma. We describe seven cases of unilateral
      vestibular schwannoma in which conventional assessment was either equivocal or
      failed to demonstrate a tumour subsequently diagnosed by magnetic resonance
      imaging. Two patients with neurofibromatosis type 2 are also reported to show how
      magnetic resonance imaging confirmed the presence of a second vestibular
      schwannoma despite CT that showed only a unilateral lesion. We also illustrate
      how limited protocol MRI of patients is slightly more expensive yet much more
      cost effective than the usual battery of tests and propose that it should be the
      first line investigation for patients in whom the clinical picture requires
      exclusion of a retrocochlear lesion. Not all of these early diagnosed tumours
      have been immediately removed. In some of the more elderly or infirm patients a
      'wait and rescan' policy has been adopted. Nevertheless, the early establishment
      of the correct diagnosis facilitates the subsequent management of these patients.

PMID- 7576278
TI  - Surgical treatment of fractures of the thoracic and lumbar spine via the
      transpedicular route.
AB  - Sixty-seven consecutive patients with burst or dislocation fractures of the
      thoracic or lumbar spine were submitted to early surgical reduction, via the
      transpedicular route, over a 5-year period. The first 22 patients received
      Harrington instrumentation, while transpedicular devices were applied in the last
      44 cases, at either the thoracic or the lumbar level. One patient did not receive
      any spinal instrumentation. This surgical approach was found to be reliable in
      achieving a near-anatomical reconstruction of the fractured spinal segment. The
      rate of post-operative complications was low. Placement of transpedicular devices
      proved to be a safe and effective procedure. The overall results were consistent
      with the thesis that the transpedicular approach compares favourably with
      alternative surgical methods.

PMID- 7576279
TI  - Transcranial Doppler ultrasonography in hydrocephalic children with tuberculous
      meningitis.
AB  - Studies have shown a close correlation between congenital hydrocephalus (CH) and
      the Gosling pulsatility index (PI) determined by transcranial Doppler
      ultrasonography (TCD). There have not previously been similar studies in children
      with hydrocephalus from tuberculous meningitis (TBM), and in particular where
      arteritis is a prominent feature. Fifteen children from each of these two groups
      were prospectively examined by TCD before and after CSF diversion. Fifteen
      children without hydrocephalus were similarly evaluated as controls. The fall in
      PI following surgery was compared. The mean fall in PI in the congenital
      hydrocephalic group was 0.723 (SD, 0.42) as compared with 0.089 (SD, 0.16) in the
      TBM group (p = 0.0001). Ten of the 15 children in the TBM group had infarcts
      revealed by CT. In these, the PI significantly postoperatively (p = 0.004),
      (0.014; SD, 0.12) when compared with values obtained (0.24; SD, 0.11) in five
      children without infarcts. These findings indicate that the clinically relevant
      fall in PI following CSF diversion in children with congenital hydrocephalus does
      not necessarily occur in children with hydrocephalus secondary to TBM, especially
      when complicated by cerebral infarcts.

PMID- 7576280
TI  - Laser-assisted flexible endoscopic fenestration of giant cyst of the septum
      pellucidum.
AB  - The use of the flexible neuroendoscope and laser fenestration in the surgical
      management of a symptomatic cyst of cavum septum pellucidum is reported.
      Successful communication was established between the cyst cavity and the lateral
      ventricles using this technique. Satisfactory clinical and radiological
      improvement as seen on MRI confirmed the operative success.

PMID- 7576283
TI  - Type I Chiari deformity presenting with profound sinus bradycardia: case report
      and literature review.
AB  - Type I Chiari deformity presents with diverse symptoms and signs which can be
      attributed to compression of structures at the foramen magnum. Bradycardia as a
      result of medullary compression has not been reported previously. A patient is
      described with type I Chiari deformity who presented with episodic profound sinus
      bradycardia for which a pacemaker was inserted before the diagnosis of cerebellar
      ectopia was finally made. Surgical decompression proved curative.

PMID- 7576281
TI  - Chronic simultaneous bilateral extradural haematomas.
AB  - Bilateral extradural haematomas are rare, usually acute, and generally associated
      with severe trauma and a high mortality. We report the case of a 39-year-old man
      who presented with chronic simultaneous bilateral extradural haematomas in whom
      the trauma appeared to be trivial and initially unrecognised and in whom a
      unilateral evacuation was curative.

PMID- 7576284
TI  - Acute intracranial subdural haematoma resulting from lumbar myelography.
AB  - We report a case of acute intracranial subdural haematoma after lumbar
      myelography with Iopamidol. The haematoma was successfully treated by emergency
      craniotomy. The bleeding came from cortical bridging veins as confirmed by
      surgery. This rare complication should be suspected in patients who complain of
      prolonged headache or develop a neurological deficit after myelography.

PMID- 7576282
TI  - Peripheral aneurysms of the anterior inferior cerebellar artery. Case report and
      review of literature.
AB  - Distal anterior inferior cerebellar artery aneurysms are rare. We recently
      treated one of these in a 46-year-old woman suffering from SAH and right facial
      and auditory deficit. The aneurysm was trapped 3 weeks after haemorrhage. Review
      of the pertinent literature revealed 36 similar cases which we analysed in
      detail. Guidelines for the proper management of these rare lesions are outlined.

PMID- 7576285
TI  - Sinus histiocytosis with massive lymphadenopathy localized to the sella.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) is a condition of unknown
      aetiology characterized by proliferation of histiocytes and lymphocytes, with the
      former phagocytosing the latter producing a typical histological appearance.
      Although first described in lymph nodes, cases have been reported in many
      extranodal sites, including the central nervous system. We report a case of SHML
      involving the sella turcica producing diabetes inspidus and pituitary
      dysfunction.

PMID- 7576286
TI  - Solitary intradural intracranial osteoma.
AB  - A 20-year-old woman presented with a 4-month history of persistent right
      frontotemporal headache. There were no features of raised intracranial pressure.
      Plain radiographs of the skull showed a dense calcified mass in the right frontal
      area. Computed tomography revealed the lesion to be uniformly hyperdense and non
      enhancing. Magnetic resonance imaging confirmed the dural origin of the lesion
      which was hyperintense and non-enhancing. At operation a bony hard intradural
      mass was confirmed and excised. Histology revealed it to be an osteoma.

PMID- 7576288
TI  - Midline approach to aneurysms: an unusual complication.

PMID- 7576287
TI  - A foreign body reaction to Surgicel(R) mimicking an abscess or tumour recurrence.

PMID- 7576289
TI  - Thoracic intradural lipoma.

PMID- 7576290
TI  - Malignant inverted papilloma of the urinary bladder: the histopathological aspect
      of malignant potential of inverted papilloma.
AB  - To investigate the histopathological characteristics of inverted papillomas of
      the urinary bladder, including the possibility of malignant transformation, we
      studied the indicators of cellular proliferation activity in 7 inverted
      papillomas of the bladder including two cases of malignant inverted papilloma of
      the bladder. PCNA expression rates in two cases of malignant inverted papilloma
      were higher than in benign inverted papillomas. Mean numbers of AgNORs per
      nucleus in malignant inverted papillomas were much more than in benign inverted
      papillomas. The c-erbB-2 oncoprotein was expressed only in malignant inverted
      papillomas. These results suggest that PCNA expression rate, mean number of
      AgNORs per nucleus and c-erB-2 oncoprotein expression may be merited as good
      indicators to detect the inverted papilloma with more proliferative and
      aggressive lesions, and with the potential of malignant transformation.

PMID- 7576291
TI  - Preoperative chemoradiotherapy for locoregional esophageal cancer: preliminary
      report.
AB  - Conventional treatment of esophageal cancer with surgery or radiation alone has
      afforded few long-term survivors. In order to improve outcome and determine the
      efficacy of a combined modality approach, this prospective study was performed.
      Between May 1993 and August 1994, 27 patients with loco-regional squamous cell
      carcinoma of the esophagus were treated with 2 courses of combined
      fluorouracil(1000mg per square meter of body-surface area daily for 5 days) and
      cisplatin(60mg per square meter on the first day)(D1 and D29) plus 48Gy of
      radiation therapy(RT) over 4 weeks. A transhiatal esophagectomy was planned 3-4
      weeks after chemoradiotherapy. Twenty-seven patients completed a full course of
      therapy. Clinical response was evaluable in 26 patients: 22 patients showed
      improvement and relief from dysphagia, 2 patients stable disease, and 2 patients
      progression. One patient died of sepsis 1 week after completion of
      chemoradiotherapy and was excluded from the analysis. Ten patients underwent
      operation after chemoradiation. Of them, 5 showed complete histologic response.
      One of the complete responders died of recurred disease 8.5months after
      operation, the other 2 patients died of sudden death, and sepsis from wound
      deheiscence 7 days after operation, respectively. Nine patients refused operation
      because of excellent relief of their dysphagia and 6 patients were denied because
      of disease progression(2), fear of operations(2), old age and family member's
      disapprovement(1), and underlying liver cirrhosis(1). The last one patient was
      awaiting for operation. Of 13 patients who refused or denied operation, 6
      patients finished further chemotherapy and radiatherapy(external radiation 1200
      cGy+intracavitary radiation 900 cGy, 2 cycles of 5FU+cisplatin). This intensive
      preoperative chemoradiotherapy is feasible, and allows for a high rate of
      resectability and a high rate of complete pathologic response in a locoregional
      esophageal cancer. Toxicity is considerable but manageable. This study warrants
      further investigation.

PMID- 7576292
TI  - Relation between ischemic preconditioning and the duration of sustained ischemia.
AB  - It has been reported that repetitive brief periods of ischemia and reperfusion
      (ischemic preconditioning, IP) cause a significant reduction in the extent of
      myocardial necrosis or in the incidence of reperfusion arrhythmias in rat heart.
      However, recent reports have stated that IP effect is diminished or lost in the
      canine or bovine heart if ischemia (mostly regional) is sustained for 40 min or
      longer. The main objective of this study is to assess whether IP provides
      myocardial protection in prolonged sustained ischemia under the condition of
      global ischemia in isolated rabbit heart. The hearts were subjected to 10-60 min
      sustained ischemia (SI) followed by 60 min reperfusion with (IP heart) or without
      IP (ISCH heart). IP was induced by 4 cycles of 5 min global ischemia and 5 min
      reperfusion. Left ventricular function (LVF), extent of infarction (EI) and
      ultrastructural changes were examined. As a whole, the LVF began to recover on
      reperfusion but there was no significant difference in the functional parameters.
      However, extracellular Ca2+ concentration was lower in the ISCH hearts (p < 0.05)
      and the EI was significantly different between the hearts which had received 60
      min SI (67% in the ISCH versus 32% in the IP heart, p < 0.01). Ultrastructural
      changes were homogeneous in the ISCH hearts and became irreversible in accordance
      with increase of the duration of ischemia, while these changes were heterogeneous
      and restricted in the IP heart. These results suggest that IP does not attenuate
      the postischemic dysfunction in prolonged ischemia but it can provide an infarct
      size-limiting effect and delay ultrastructural changes. This cardioprotective
      effect may be related to calcium homeostasis.

PMID- 7576294
TI  - Extensive colonic stricture due to pelvic actinomycosis.
AB  - A 36-year-old woman presented with a palpable tender mass at the left lower
      quadrant of the abdomen. She had suffered from constipation for five years and
      had a previous history of intrauterine device-use for one year. Preoperative
      barium enema and abdominopelvic CT showed a compatible finding of rectosigmoid
      colon cancer or left ovary cancer. She underwent segmental resection of the
      sigmoid colon along with the removal of left distal ureter, left ovary and
      salpinx. Pathologic examination revealed actinomycotic abscesses containing
      sulfur granules. Thereafter, she took parenteral ampicillin (50mg/kg/day) for one
      month and oral amoxicillin (250mg, tid) for 2 months consecutively. The patient
      has no specific problems for 6 months after surgical resection and long-term
      antibiotic therapy. This report may be the first of intrauterine device
      associated pelvic actinomycosis involving both sigmoid colon and rectum
      extensively.

PMID- 7576293
TI  - Bilateral renal cortical necrosis with the changes in clinical features over the
      past 15 years (1980-1995).
AB  - A rare case of bilateral renal cortical necrosis (BRCN) diagnosed only by the
      characteristic and specific findings of a contrast-enhanced CT scan during the
      acute initial phase of the disease is presented in this paper. Furthermore,
      twenty-eight patients of BRCN in the world literatures in English after 1980 were
      analyzed to investigate the changes in its clinical features over the past 15
      years in comparison with the reported data before 1980 from two large centers in
      France (F) and India (I). Obstetric causes decreased from 68% (F) and 71% (I)
      before 1980 to 28% after 1980, whereas nonobstetric causes increased from 32% (F)
      and 29% (I) to 72% after 1980. Among the nonobstetric causes of BRCN, the leading
      causes were sepsis in 4 out of 12 patients (F) and snake bite in 6 out of 14
      patients (I) before 1980, but, in contrast, drugs in 4 out of 21 patients after
      1980. As a definite diagnostic procedure for BRCN, 95 to 100% before 1980 but 86%
      after 1980 performed renal biopsy, of which renal biopsy while living was done in
      only 42% (F) and 16% (I) before 1980 and 67% after 1980. None showed renal
      calcification in abdominal X-ray, and only 25% (3/12) had nonspecific echo
      findings in renal ultrasonography, whereas the high sensitivity for BRCN was
      noted in renal arteriography in 100% (6/6) and contrast-enhanced CT scan in 88%
      (7/8). The mortality of BRCN decreased from 55% (F) and 86% (I) before 1980 to
      36% after 1980. This review of BRCN, in conclusion, revealed the distinctive
      changes over the past 15 years in the etiology with a higher incidence of non
      obstetric causes than obstetric ones, diagnostic procedures with less dependence
      on renal biopsy but new trials of non-invasive radioimagings including CT scan
      and even MRI, and a further declining mortality rate.

PMID- 7576295
TI  - A small cell osteosarcoma on the calcaneus--a case report.
AB  - Small cell osteosarcoma is rare, representing 1-4% of all osteosarcomas. We
      experienced a case of small cell osteosarcoma in an 8-year-old girl on her
      calcaneus. Histologically, the tumor consists of small round cells that resemble
      those of Ewing's sarcoma, and variable foci of lacy osteoid formation between
      tumor cells. The rare location, histologic characteristics and differential
      diagnostic points are discussed.

PMID- 7576296
TI  - Trauma-induced isomorphic lesions in morphea--a brief case report.
AB  - We describe a case of morphea which presented further typical lesions of the
      disease at the sites of mechanical trauma. It can be suggested that cutaneous
      lesions of morphea may be locally developed due to physical stimuli as an
      isomorphic response in patients or subclinical cases of the disease.

PMID- 7576298
TI  - 1991 cancer incidence in Seoul, Korea: results of the Implementation Study of the
      Seoul Cancer Registry.
AB  - This article presents the results of the Implementation Study of the Seoul Cancer
      Registry, which started in July, 1991 as a population based cancer registry in
      Seoul, Korea. The completeness and validity of the registered data were evaluated
      using Mortality/Incidence ratio (M/I ratio), Histologically Verified Cases (HV%),
      Primary Site Uncertain (PSU%), and Age Unknown (Age UNK%). Owing to the
      additional active surveillance, the completeness of the data turned out to be
      fairly acceptable, except for the aged over 75(Mortality/Incidence ratio was over
      100%). Eventhough the Seoul cancer registry(SCR) has further way to go in the
      completeness especially among elderly persons, the validity of SCR data was also
      acceptable in terms of HV%, PSU%, and Age UNK%. However, PSU% and Age UNK% might
      need to be further reduced to be comparable with other well established cancer
      registries. The age standardized incidence rates(ASR) of all cancers between July
      1, 1991 and June 30, 1992 were 232.4/100,000 in males and 147.9/100,000 in
      females. The top five major sites of cancers in Seoul were the stomach, liver,
      lung, colo-rectum, and bladder in order in males, and the uterine cervix,
      stomach, breast, colo-rectum, and liver in females. Those 5 cancer sites
      comprised 68.9% and 64.7% of the total cancer incidence in males and females,
      respectively.

PMID- 7576299
TI  - Oncogene interaction in basal cell carcinomas of human skin.
AB  - The expression of the p53 protein (p53) was compared with those of several
      oncogenes including c-fos (Fos), c-jun (Jun), and epidermal growth factor
      receptor (EGFR1) using immunohistochemistry in frozen and paraffin-embedded
      sections of 25 basal cell carcinomas (BCCs) to find out any correlation between
      p53 and oncogenes in the pathogenesis of human BCC. In normal skin, positive
      reactions were obtained for EGFR1 and Fos, while p53 and Jun were negative in all
      cases. In the lesions, EGFR1 was observed in all cases and p53 was positive in 9
      of 25 (36%). Fos was expressed in 21 of 25 (84%) and four negative cases were all
      p53-positive; this negative correlation between p53 and Fos staining was
      statistically significant (P < 0.01). Jun was detected in 14 of 20 (70%) and no
      significant relationship was observed between the expression of Jun and Fos or
      p53. These data suggest the possibility of down regulation of Fos expression by
      high levels of p53 protein. Further work is necessary to determine the mechanism
      of this interaction.

PMID- 7576297
TI  - Nationwide incidence estimation of lung cancer in Korea.
AB  - The aim of this paper is to estimate the nationwide incidence rate of lung cancer
      in Korea. The potential incident cases were identified by hospital visiting and
      mailing, based on the ICD-9 diagnostic codes on the claims as one of the
      following: ICD-9 162-165 (malignant neoplasms of the respiratory system), 212
      (benign neoplasm), 231 (carcinoma in situ), 511 (pleurisy), or 195-199 (malignant
      neoplasms with uncoded sites) in beneficiaries data of the Korea Medical
      Insurance Corporation from January, 1988 to December, 1989. Thereafter, the
      identified cases were confirmed by an oncologist (Dr. DS Heo). When adjusted with
      age distribution of the Korean population based on the 1985 Population Census,
      the incidence rate was 22.3 per 100,000 in males (95% CI: 21.70-23.01) and 8.37
      (95% CI: 7.97-8.78) in females in 1989. And the age-adjusted rate for the world
      population was 39.63 in males and 9.95 in females.

PMID- 7576300
TI  - Differentiation of malignant from benign pancreatic mass by Tl-201 abdominal
      SPECT.
AB  - The aim of the present study was to evaluate the ability of Tl-201 abdominal
      SPECT to differentiate between chronic focal pancreatitis and pancreatic
      malignancy. Seventeen patients (12 men, 5 women; mean age, 56 years; 9 pancreatic
      cancer, 8 chronic pancreatitis) with pancreatic mass were prospectively
      investigated with Tl-201 abdominal SPECT. In all patients, CT and/or US could not
      clarify the nature of the pancreatic mass. Focal hot uptake was present in 8 of 9
      patients with pancreatic cancer, while it was present in 2 of 8 patients with
      chronic pancreatitis. Therefore, the sensitivity and specificity of the present
      study were 89% and 75%, respectively. A significant difference of Tl-201 uptakes
      was noted between benign and malignant masses (p < 0.05). Therefore, we concluded
      that Tl-201 abdominal SPECT was a useful test in differentiation of malignant
      from benign pancreatic mass, especially when the differentiation could not be
      made by other imaging modalities.

PMID- 7576301
TI  - Expression of the nucleoside diphosphate kinase in human skin cancers: an
      immunohistochemical study.
AB  - Expression of nucleoside diphosphate(NDP) kinase, which is homologous to the nm23
      gene product in a variety of species, has been found to be inversely associated
      with metastatic potential. However, the relationship remains controversial
      according to the tumor cell types and experimental system, with conflicting
      results from different research groups. In order to determine whether NDP kinase
      expression serves as a marker for metastatic potential in human skin cancer, we
      assessed the levels of NDP kinase expression in 9 keratoacanthomas (KAs), 26
      squamous cell carcinomas (SCCs), and 25 basal cell carcinomas (BCCs) using
      immunohistochemistry. The expression of NDP kinase was intense in KA and SCC
      compared with BCC. However, the difference of NDP kinase expression between KA
      and SCC was not statistically significant. And there was no statistically
      significant difference in NDP kinase expression between SCC with metastasis and
      SCC without metastasis. Our results contradict the hypothesis concerning the
      possible role of nm23 gene as a metastatic suppressor gene in human skin cancer.
      The mechanism of overexpression in various tumor cell types and its biological
      significance in cutaneous carcinogenesis remain to be determined.

PMID- 7576302
TI  - Treatment of PC12 cells by nerve growth factor, dexamethasone, and forskolin.
      Effects on cell morphology and expression of neurotensin and tyrosine
      hydroxylase.
AB  - Several lines of anatomical, neurochemical, electrophysiological, and behavioral
      evidence suggest the existence of physiological interactions between neurotensin
      (NT) and the brain dopaminergic systems. Thus, NT has been shown to exert a
      neuroleptic-like action and could be implicated in the pathogenesis and treatment
      of schizophrenia. It is thus of particular importance to develop in vitro cell
      culture systems as models to study such interactions. Rat adrenal
      pheochromocytoma PC12 cells, which expressed high levels of tyrosine hydroxylase,
      were used in the present study. In contrast to rat brain cells in primary
      cultures, PC12 cells did not express functional NT receptors. However, they were
      able to express both NTmRNA and NT in response to NGF, forskolin, and
      dexamethasone. Those neurochemical modifications furthermore may be related to
      changes in the morphology of the PC12 cells in response to NGF, forskolin, and
      dexamethasone alone or in combination. These data suggest that PC12 cells may
      provide a useful model to study in vitro the regulation of both catecholamine and
      neurotensin phenotypes.

PMID- 7576303
TI  - VIP as a cell-growth and differentiation neuromodulator role in neurodevelopment.
AB  - In addition to its commonly recognized status as a neuromodulator of virtually
      all vital functions, including neurobiological, the neuropeptide VIP plays a role
      in the control of cell growth and differentiation and of neuronal survival.
      Through these actions, VIP, whose impact appears early in ontogeny, may possess
      developmental functions. VIP can be stimulatory or inhibitory on cell growth in
      function of the model considered. The growth regulatory actions of VIP, which are
      often independent of cAMP, are most likely significant when mitogenic or trophic
      factors, eventually released by nontarget cells, are simultaneously present in
      the extracellular medium. The intracellular mechanisms that mediate these actions
      of VIP may involve different transduction cascades triggered by subsets of VIP
      binding sites that may coexist in the same tissue.

PMID- 7576305
TI  - Maintaining the neuronal phenotype after injury in the adult CNS. Neurotrophic
      factors, axonal growth substrates, and gene therapy.
AB  - Multiple genetic and epigenetic events determine neuronal phenotype during
      nervous system development. After the mature mammalian neuronal phenotype has
      been determined it is usually static for the remainder of life, unless an injury
      or degenerative event occurs. Injured neurons may suffer one of three potential
      fates: death, persistent atrophy, or recovery. The ability of an injured adult
      neuron to recover from injury in adulthood may be determined by events that also
      influence neuronal phenotype during development, including expression of growth
      related genes and responsiveness to survival and growth signals in the
      environment. The latter signals include neurotrophic factors and substrate
      molecules that promote neurite growth. Several adult CNS regions exhibit
      neurotrophic-factor responsiveness, including the basal forebrain, entorhinal
      cortex, hippocampus, thalamus, brainstem, and spinal cord. The specificity of
      neurotrophic-factor responsiveness in these regions parallels patterns observed
      during development. In addition, neurons of several CNS regions extend neurites
      after injury when presented with growth-promoting substrates. When both
      neurotrophic factors and growth-promoting substrates are provided to adult rats
      that have undergone bilateral fimbria-fornix lesions, then partial morphological
      and behavioral recovery can be induced. Gene therapy is one useful tool for
      providing these substances. Thus, the mature CNS remains robustly responsive to
      signals that shape nervous system development, and is highly plastic when
      stimulated by appropriate cues.

PMID- 7576304
TI  - Regulation of neuropeptide expression in the brain by neurotrophins. Potential
      role in vivo.
AB  - Neurotrophins, which are structurally related to nerve growth factor, have been
      shown to promote survival of various neurons. Recently, we found a novel activity
      of a neurotrophin in the brain: Brain-derived neurotrophic factor (BDNF) enhances
      expression of various neuropeptides. The neuropeptide differentiation activity
      was then compared among neurotrophins both in vivo and in vitro. In cultured
      neocortical neurons, BDNF and neurotrophin-5 (NT-5) remarkably increased levels
      of neuropeptide Y and somatostatin, and neurotrophin-3 (NT-3) also increased
      these peptides but required higher concentrations. At elevating substance P,
      however, NT-3 was as potent as BDNF. In contrast, NGF had negligible or no
      effect. Neurotrophins administered into neonatal brain exhibited slightly
      different potencies for increasing these neuropeptides: The most marked increase
      in neuropeptide Y levels was obtained in the neocortex by NT-5, whereas in the
      striatum and hippocampus by BDNF, although all three neurotrophins increased
      somatostatin similarly in all the brain regions examined. Overall spatial
      patterns of the neuropeptide induction were similar among the neurotrophins.
      Neurons in adult rat brain can also react with the neurotrophins and alter
      neuropeptide expression in a slightly different fashion. Excitatory neuronal
      activity and hormones are known to change expression of neurotrophins. Therefore,
      neurotrophins, neuronal activity, and hormones influence each other and all
      regulate neurotransmitter/peptide expression in developing and mature brain.
      Physiological implication of the neurotransmitter/peptide differentiation
      activities is also discussed.

PMID- 7576307
TI  - Protein-DNA interactions during phenotypic differentiation.
AB  - We have been studying the molecular mechanism of neuronal differentiation through
      which the multipotent precursor becomes limited to the final transmitter
      phenotype. Here we focused on the role of the 5' proximal regulatory cassette (
      190; +53 bp) of the rat enkephalin (rENK) gene in the developmental regulation of
      the enkephalin phenotype. Several well characterized cis-elements, including AP2,
      CREB, NF1, and NFkB, reside on this region of the rENK gene. These motifs were
      sufficient to confer activity-dependent expression of the gene during
      neurodifferentiation when it was tested using transient transfection assays of
      primary developing spinal cord neurons treated with tetrodotoxin (TTX). This
      region was then used as a DNA probe in mobility shift assays, with nuclear
      proteins derived from phenotypically and ontogenetically distinct brain regions.
      Only a few low abundance protein-DNA complexes were detected and only with
      nuclear proteins derived from developing but not from adult brain. The
      spatiotemporal pattern of these complexes did not show correlation with
      enkephalin expression which was assessed by RT-PCR. We employed synthetic probes
      corresponding to consensus as well as ENK-specific sequences of the individual
      motifs to identify the nature of the observed bands. Although both consensus NF1
      and enkCRE1(NF1) formed complexes with nuclear proteins derived from the striatum
      and cortex at various ages, the appearance of the bands was not correlated with
      ENK expression. Surprisingly, no complexes were detected if other ENK-specific
      motifs were used as probes. We also tested nuclear extracts derived from
      forskolin-induced and control C6 glioma cells, again using the whole proximal
      regulatory cassette as well as individual motifs. These experiments showed the
      formation of elaborate protein-DNA bands. There was no direct correlation between
      the appearance of bands and forskolin-induced ENK expression. Unexpectedly, all
      ENK-specific motifs formed specific and highly abundant protein-DNA complexes
      when nuclear extracts from the human tumor cell line (HeLa), which does not
      express ENK, were used. Based on these observations, we concluded that: 1.
      Interactions between the proximal regulatory cassette and additional probably far
      distant regions of the rENK gene and their binding proteins may be necessary to
      confer developmentally regulated, cell-specific expression of the ENK gene; and
      2. Inducibility of the gene by common cis-elements can be governed by this
      region; however, the cell-specificity of the induction remains elusive.

PMID- 7576310
TI  - The Neuronal Phenotype; Molecular Biology, Cell Specification, and Therapeutic
      Frontiers. Proceedings of a symposium. Lozari, Corsica, France, August 19-20,
      1993.

PMID- 7576308
TI  - Transgenic targeting of neuroendocrine peptide genes in the hypothalamic
      pituitary axis.
AB  - A large number of neuroendocrine peptide genes have been tested for their ability
      to target expression to the hypothalamus and pituitary in transgenic mice. This
      has resulted in a number of powerful applications, for example, ablation or
      immortalization of specific cell types, and analysis of transcription regulatory
      sequences. The greatest amount of success in targeting cells of the
      neuroendocrine axis has been in the pituitary and has utilized regulatory
      sequences of genes that are normally expressed in pituitary. Greater difficulties
      have been encountered in directing expression to specific neurons in the
      hypothalamus. A primary goal of this review is to consider collectively the data
      obtained by a number of laboratories in order to draw conclusions about the
      general sequence requirements for achieving cell-specific expression. The data
      suggest that the mechanisms controlling cell-specific expression of neuropeptide
      genes in the hypothalamus are complex and involve multiple regulatory elements
      that may reside within the gene or many kilobases away from the promoter. These
      elements act positively and negatively in different cells to enhance or restrict
      expression, and may include sequences that shield a transgene from regulatory
      influences of other genes near the point of chromosomal insertion.

PMID- 7576306
TI  - Retinoic acid and retinoic acid receptors in development.
AB  - The vitamin A derivative retinoic acid (RA) and related compounds (retinoids) are
      utilized as signaling molecules in a diverse array of developmental and
      physiological regulatory processes, including many important in the developing
      and mature nervous system. Retinoids function by interaction with high affinity
      receptors of the nuclear receptor family, which also mediate the effects of
      steroid and thyroid hormones and which act in the nucleus as transcription
      factors. This review summarizes current knowledge of the molecular mechanisms of
      retinoid action, the complex role of retinoid receptors in a variety of hormonal
      signaling processes, and illustrates current efforts to more fully understand the
      biological functions of retinoid receptors through analysis of downstream gene
      regulatory networks and studies of mouse gene knockout systems.

PMID- 7576309
TI  - Brief overview of control of genetic expression by antisense oligonucleotides and
      in vivo applications. Prospects for neurobiology.
AB  - Over the past several years, the use of synthetic oligonucleotides and functional
      analogs thereof as a possibly general means of controlling genetic expression has
      received widespread attention. Following a brief overview of some of the basic
      principles and strategies for this approach, attention is focused here on
      summarizing some recent reports of in vitro and, in particular, in vivo
      investigations in various animal models using phosphorothioate analogs of 2'
      deoxyoligonucleotides. In view of these findings, which include studies related
      to neurobiology, this field should find significant utility in applications of
      the antisense method for controlling genetic expression.

PMID- 7576314
TI  - Calcium oxalate monohydrate renal calculi. Formation and development mechanism.
AB  - Available information relevant to stone genesis on both calcium oxalate
      monohydrate crystallization and fine inner structure of papillary calculi is
      reviewed. Integration of attained facts facilitated formulating a feasible
      mechanism of papillary calculi formation and development. Medical implications of
      this mechanism are assessed.

PMID- 7576313
TI  - Thermodynamics of micellar systems: comparison of mass action and phase
      equilibrium models for the calculation of standard Gibbs energies of micelle
      formation.
AB  - Micellar colloids are distinguished from other colloids by their association
      dissociation equilibrium in solution between monomers, counter-ions and micelles.
      According to classical thermodynamics, the standard Gibbs energy of formation of
      micelles at fixed temperature and pressure can be related to the critical micelle
      concentration. This relation is different for two models which are widely used to
      describe micelle formation, namely the Phase Separation and the Mass Action
      Models. These approaches and the assumptions upon which they are based are
      analysed in this paper. We show that the two models can be generalised to include
      surfactant salts having different stoichiometries.

PMID- 7576315
TI  - AIDS behind bars: preventing HIV spread among incarcerated drug injectors.

PMID- 7576311
TI  - Genetic mechanisms of early neurogenesis in Drosophila melanogaster.
AB  - The neurogenic ectoderm of Drosophila melanogaster consists of the ventral
      neuroectoderm and the procephalic neuroectoderm. It is hypothesized that
      epidermal and central neural progenitor cells separate from each other in three
      steps: conference on the neuroectodermal cells the capability of producing neural
      or epidermal progenies, separation of the two classes of progenitor cells, and
      specification of particular types of neuroblasts and epidermoblasts. Separation
      of neuroblasts and epidermoblasts is controlled by proneural and neurogenic
      genes. Delta and Notch serve as mediators of direct protein-protein interactions.
      E(SPL)-C inhibits neurogenesis, creating epidermal cells. The achaete-scute
      complex (AS-C) controls the commitment of nonoverlapping populations of
      neuroblasts and leads the development of neuroectodermal cells as neuroblasts.

PMID- 7576316
TI  - Encapsulation of foscarnet in liposomes modifies drug intracellular accumulation,
      in vitro anti-HIV-1 activity, tissue distribution and pharmacokinetics.
AB  - OBJECTIVE: To improve the in vitro anti-HIV-1 activity, intracellular
      accumulation in macrophages and in vivo pharmacokinetics and tissue distribution
      of foscarnet (trisodium phosphonoformate; PFA) by encapsulation in liposomes.
      METHODS: The accumulation of free and liposome-encapsulated PFA was determined in
      monocyte-macrophage RAW 264.7 cells and human premonocytoid U937 cells. The
      antiviral activity was evaluated in U937 cells infected with HIV-1IIIB. Tissue
      distribution and pharmacokinetics of free and liposomal PFA were determined in
      female Sprague-Dawley rats following the administration of an intravenous bolus
      dose (10 mg PFA/kg). RESULTS: The entrapment of PFA in liposomes resulted in a
      higher drug accumulation in both U937 and RAW 264.7 cells. A slightly greater
      efficacy against HIV-1IIIB replication into U937 cells was observed upon
      encapsulation of PFA into liposomes. Improved pharmacokinetics was observed upon
      entrapment of PFA in liposomes. Much higher drug levels were found in plasma for
      the liposomal formulation. The systemic clearance of the liposomal drug was 77
      times lower than that of free drug. The encapsulation of PFA in liposomes greatly
      enhanced the drug accumulation in organs of the reticuloendothelial system.
      CONCLUSION: The encapsulation of PFA in liposomes modified the tissue
      distribution and plasma pharmacokinetics of the antiviral agent, resulting in a
      marked improvement of drug accumulation in organs involved in HIV
      immunopathogenesis and in a greater PFA bioavailability. The antiviral activity
      of liposomal PFA was slightly greater than that of free drug in HIV-1IIIB
      infected U937 cells.

PMID- 7576312
TI  - Neuropeptide messenger plasticity in the CNS neurons following axotomy.
AB  - Neuronal peptides exert neurohormonal and neurotransmitter (neuromodulator)
      functions in the central nervous system (CNS). Besides these functions, a group
      of neuropeptides may have a capacity to create cell proliferation, growth, and
      survival. Axotomy induces transient (1-21 d) upregulation of synthesis and gene
      expression of neuropeptides, such as galanin, corticotropin releasing factor,
      dynorphin, calcitonin gene-related peptide, vasoactive intestinal polypeptide,
      cholecystokinin, angiotensin II, and neuropeptide Y. These neuropeptides are
      colocalized with "classic" neurotransmitters (acetylcholine, aspartate,
      glutamate) or neurohormones (vasopressin, oxytocin) that are downregulated by
      axotomy in the same neuronal cells. It is more likely that neuronal cells, in
      response to axotomy, increase expression of neuropeptides that promote their
      survival and regeneration, and may downregulate substances related to their
      transmitter or secretory activities.

PMID- 7576317
TI  - Determination of HIV-1 subtypes in injecting drug users in Bangkok, Thailand,
      using peptide-binding enzyme immunoassay and heteroduplex mobility assay:
      evidence of increasing infection with HIV-1 subtype E.
AB  - OBJECTIVES: To evaluate the sensitivity and specificity of peptide-binding enzyme
      immunoassay (PEIA) and heteroduplex mobility assay (HMA) for the determination of
      HIV-1 subtypes B and E; to determine the proportions of infections due to
      subtypes B and E over time; and to generate data on DNA sequences of the C2-V3
      region of the env genes. METHODS: HIV-1 subtyping was conducted by PEIA and HMA
      on blood specimens obtained from 97 injecting drug users (IDU) infected with HIV
      between 1988 and 1993. Genetic sequencing was performed on 84 specimens. RESULTS:
      Both laboratory methods were highly sensitive and specific for the determination
      of HIV-1 subtypes B and E. The two tests were complementary; samples which could
      not be typed by HMA were correctly typed by PEIA and vice versa. While subtype B
      accounted for 80.4% (78 out of 97) of infections overall, the proportion of new
      infections due to subtype E increased from 2.6% (one out of 38) in 1988-1989 to
      25.6% (11 out of 43) in 1990-1991, and to 43.8% (seven out of 16) in 1992-1993
      (chi 2 for linear trend, P < 0.001). CONCLUSIONS: HMA and PEIA are practical,
      sensitive and specific laboratory methods for the determination of HIV-1 subtypes
      in Thailand, and may be useful in other geographic areas to define the molecular
      epidemiology of the global HIV-1 pandemic. Data suggest that the proportion
      subtype E infections have increased among Bangkok IDU from 1988 through 1993.

PMID- 7576318
TI  - The evolving molecular epidemiology of HIV-1 envelope subtypes in injecting drug
      users in Bangkok, Thailand: implications for HIV vaccine trials.
AB  - OBJECTIVE: To genetically characterize HIV-1 strains in injecting drug users
      (IDU) in Bangkok, Thailand in 1994, and compare these with strains found earlier
      in Thai IDU; such information is essential for HIV-1 vaccine development and
      evaluation. METHODS: Peripheral blood mononuclear cells were collected from 84
      IDU attending 14 drug treatment clinics in Bangkok in 1994. DNA was amplified
      using a nested polymerase chain reaction (PCR) procedure and sequenced directly
      (without cloning) from the PCR products. The V3 and flanking regions (345
      nucleotides) of the env gene were analyzed using a neighbor-joining tree.
      RESULTS: Only one (1%) strain was a typical subtype B virus, 69 (82%) were
      genetically distinct subtype B' viruses (Thai B), and 14 (17%) were subtype E
      strains (Thai A). Persons with recently acquired infection were more likely to
      have subtype E viruses (P < 0.001) than those in our 1991 survey, who were more
      likely to have subtype B' viruses. Pairwise intra-subtype differences within
      subtypes E and B' were 5.3 and 4.3%, respectively, compared with 3.4 and 3.5%
      among strains collected in 1991 in Thailand. CONCLUSION: The genetic diversity
      within subtypes B' and E in Thailand and the proportion of new infections due to
      subtype E viruses among Bangkok IDU are increasing significantly. These data
      highlight the importance of monitoring the molecular epidemiology of HIV-1 in
      populations being considered for HIV-1 vaccine trials.

PMID- 7576319
TI  - Productive HIV-1 infection of normal human mammary epithelial cells.
AB  - OBJECTIVE AND DESIGN: To determine the susceptibility of mammary epithelial cells
      (MEC) to HIV-1 as breastfeeding is an established route of HIV transmission,
      although the origin of virus in breastmilk is unclear. METHODS: Primary
      epithelial cell cultures were derived from the mammary glands of healthy donors;
      immortalized MEC lines were also used. HIV infection was followed by detection of
      infectious particle production, p24 antigen and viral sequences. RESULTS: Seven
      out of 11 primary MEC cultures and two out of three MEC lines were productively
      infected by HIV-1. Virus replication significantly reduced cell proliferation,
      although cell viability was only slightly affected. Cytopathic changes were not
      observed. MEC cultures expressed low levels of surface CD4, galactosylceramide
      and CD26, but essentially no human leukocyte antigen (HLA)-DR. Infection of HIV
      permissive MEC cells was associated with the upregulation of surface HLA-DR and
      CD26. In contrast, the expression of CD4, tissue-specific markers, adhesion
      molecules and growth-factor receptors was downregulated. To a lesser extent,
      similar effects were also observed in non-permissive cells. Hormones
      (triiodothyronine plus beta-estradiol and prolactin) enhanced HIV replication,
      possibly through the stimulation of cellular DNA synthesis. CONCLUSIONS: We
      concluded that HIV-1 replication in ductal/alveolar MEC may be, in part,
      responsible for the presence of HIV-1 in milk; that hormones may stimulate virus
      replication; and that infection reduces the growth of epithelial cells. Although
      in vitro HIV is produced by MEC to a lesser extent than lymphoid cells, MEC
      derived HIV might have selective advantages for the infection of mucosal
      epithelial cells during breastfeeding.

PMID- 7576322
TI  - Campylobacter infections in HIV-infected patients: clinical and bacteriological
      features.
AB  - OBJECTIVE: To study the clinical and bacteriological features of Campylobacter
      infections in HIV-infected patients. DESIGN: A retrospective analysis (1989
      1992), followed by a prospective analysis (1992-1994). SETTING: Hospital HIV
      inpatient unit. PATIENTS AND METHODS: All patients with Campylobacter spp.
      identified by the laboratory of microbiology at Saint-Louis Hospital, Paris were
      studied, and their clinical features as well as their response to therapy
      recorded. RESULTS: During the study period, Campylobacter infection was
      documented in 38 HIV-infected patients, 76% of whom had AIDS. Campylobacter spp.
      was isolated from stools in 36 cases and from blood cultures in four cases.
      Species identification yielded C. jejuni (84%) and C. coli (16%). High-level
      resistance to quinolones was frequently observed (21%), but resistance to
      erythromycin (3%) and tetracycline (5%) was rare. Diarrhoea, fever and abdominal
      pain were the main clinical features of infection. Other intestinal pathogens
      were found in 42% of patients. Most patients had an acute illness with rapid
      resolution under appropriate antimicrobial therapy. However, eight patients
      (21%), experienced chronic diarrhoea with persistent isolation of Campylobacter
      and in vivo selection of resistant strains, requiring multiple courses of
      antibiotics. CONCLUSIONS: Campylobacter usually cause acute diarrhoea in patients
      with HIV infection. Antimicrobial therapy should be guided on in vitro
      susceptibility testing because of the prevalence of antibiotic resistance.
      Despite appropriate therapy, some patients will present with prolonged diarrhoea
      and in vivo selection of multiresistant isolates.

PMID- 7576321
TI  - Diagnosis and prognosis of AIDS-related cholangitis.
AB  - OBJECTIVE: To determine more precisely the clinical and biological
      characteristics of AIDS-related cholangitis, and to investigate prognostic
      variables of this disease. DESIGN: Retrospective clinical and prognostic study.
      SETTING: Biliary unit, Bicetre Hospital, France. PATIENTS: HIV-positive patients
      (n = 52) referred to the unit between December 1986 and June 1993 for biliary
      symptoms leading to the suspicion of AIDS-related cholangitis, (42 men; 10 women;
      mean age, 37 +/- 8 years). INTERVENTION: Endoscopic retrograde
      cholangiopancreatography (ERCP) was performed in order to determine the cause of
      the biliary symptoms. MAIN OUTCOME MEASURE: Clinical features and evolution of
      the cholangitis. RESULTS: Among the 52 patients, 45 met the ERCP criteria of AIDS
      related cholangitis (36 men; nine women). The diagnosis of cholangitis was
      strongly suggested by abdominal ultrasonography in 47% of the cases. ERCP showed
      papillary stenosis, diffuse cholangitis, extrahepatic cholangitis alone, and
      intrahepatic cholangitis alone in 60, 67, 7 and 27%, respectively. Endoscopic
      sphincterotomy was performed in 28 patients. Pain was relieved by sphincterotomy
      in nine patients, but the other clinical or biological features were not
      influenced. One-year and 2-year survival rates were 41 +/- 7% and 8 +/- 4%,
      respectively. Multidimensional analysis using a Cox model showed that a
      lymphocyte count > 500 x 10(6)/l was the only independent predictive factor of
      better survival. CONCLUSION: AIDS-related cholangitis is a disease which leads
      preferentially to papillary stenosis or diffuse abnormalities of the biliary
      tract. Prognostic factors depend on the stage of the HIV infection. Another
      diagnosis of cholestasis was found in approximately 15% of the patients who
      showed biliary symptoms.

PMID- 7576320
TI  - Neutralization of primary HIV-1 isolates by anti-envelope monoclonal antibodies.
AB  - OBJECTIVE: To evaluate human monoclonal antibodies (MAb) for neutralizing
      activity against primary HIV-1 isolates in peripheral blood mononuclear cells.
      DESIGN: Neutralization activity data were obtained from 11 laboratories on a
      coded panel consisting of six human MAb to HIV envelope V3, CD4-binding region or
      gp41. Hyperimmune globulin against HIV-1 and normal human immunoglobulin G were
      supplied as controls. Each laboratory received pre-titered virus for use in the
      studies. METHODS: Each laboratory measured neutralization of the MAb against
      laboratory strain HIVMN, genomic clone HIVJR-CSF, two subtype B and one subtype D
      primary isolates. RESULTS: The titers of the centrally supplied virus stocks as
      determined by re-titration or back-titration varied among laboratories and were
      generally 10-100-fold less than provided. The neutralizing activity of each MAb
      varied by as much as a 1000-fold among laboratories. These differences may result
      from varying sensitivity in neutralization assay protocols and the differing
      susceptibility of primary cells to infection with HIV-1. CONCLUSIONS: To
      consolidate the data from multiple laboratories, the neutralization titers were
      compared by classifying antibodies as neutralizing if the antibody concentration
      for 50% virus inhibition was < or = 10 micrograms/ml. By this criterion, the CD4
      binding region and gp41 MAb neutralized all four subtype B viruses and the
      subtype D isolate in a few of the laboratories. The V3 MAb neutralized only HIVMN
      and the closely related HIVJR-CSF viruses.

PMID- 7576323
TI  - Micronutrient levels in HIV-1-infected children.
AB  - OBJECTIVE: Micronutrients (zinc, copper, selenium, vitamin A, E, and carotenoids)
      are essential for the integrity of host defences. This study was designed to
      determine the prevalence of abnormalities of the micronutrient levels in HIV-1
      seropositive children. DESIGN: Prospective study. SETTING: The study was
      performed on HIV-1-infected children at the Paediatric Haematology and Oncology
      Unit of Toulouse Hospital, France. PATIENTS: Twenty-one children, suffering from
      HIV-1 infection and 21 control subjects of similar age (2-9 years) were included
      in the study. In the HIV-1-infected children, two subgroups were considered
      according to stage (non-AIDS or AIDS), based on the Centers for Disease Control
      and Prevention 1987 criteria. RESULTS: The first statistically significant
      deficiencies occurred at non-AIDS stage and were confirmed at AIDS stage: P <
      0.05 for lycopene, retinol, tocopherol and P < 0.001 for transthyretin and serum
      albumin. Levels of copper (40%) and long-chain polyunsaturated fatty acids (21%)
      were higher in the non-AIDS group than the controls. CONCLUSION: Biological
      impairing of the micronutrient levels was observed in the non-AIDS stage without
      clinical sign. This information is useful in delineating eventual and well
      considered nutritional intervention strategies that may improve the clinical
      status of HIV-1-infected children and perhaps alter the course of their disease.

PMID- 7576324
TI  - Nested polymerase chain reaction for diagnosis and monitoring treatment response
      in AIDS patients with tuberculous meningitis.
AB  - OBJECTIVE: To investigate the usefulness of polymerase chain reaction (PCR) from
      cerebrospinal fluid (CSF) for rapid diagnosis and assessing treatment response of
      tuberculous meningitis (TBM) in AIDS patients. PATIENTS: Forty-four CSF samples
      from 10 patients with TBM confirmed by autopsy or by a culture of CSF (41
      samples) and from two patients with highly probable TBM (three samples) were
      analysed. CSF specimens were collected before and during standard antituberculous
      treatment. CSF samples from 24 AIDS patients with autopsy evidence of other
      neurologic diseases were studied as controls. METHODS: A nested PCR amplifying a
      123 base-pair fragment of the IS6110 sequence was developed. Heating to 95
      degrees C for 15 min was used for pre-PCR treatment of samples. RESULTS:
      Detection limit was 10(2) colony-forming units per ml or 10 fg purified
      Mycobacterium tuberculosis DNA. M.tuberculosis DNA was detected in CSF from all
      the 12 confirmed or highly probable TBM cases. CSF was positive by nested PCR in
      17 of 17 (100%) and 18 of 27 (67%) samples collected before and during therapy,
      respectively. Clinical and microbiological follow-up > or = 2 weeks was available
      for seven patients. PCR-positive CSF converted to M. tuberculosis DNA negative in
      four patients that showed improvement during treatment, but it remained positive
      in three patients who died of disseminated tuberculosis. All the CSF samples from
      the non-TBM controls were negative by nested PCR. CONCLUSIONS: Nested PCR for
      detection of M. tuberculosis DNA is specific for diagnosis of TBM and more
      sensitive than conventional bacteriology. Moreover, nested PCR could be a useful
      method for assessing treatment response in AIDS patients with TBM.

PMID- 7576325
TI  - Effects of aerosolized pentamidine on glucose homeostasis and insulin secretion
      in HIV-positive patients: a controlled study.
AB  - OBJECTIVE: Intravenous pentamidine induces hypo- and hyperglycaemia (dose
      dependent toxicity on islet beta cells), pancreatitis and nephrotoxicity.
      Conversely, aerosolized pentamidine (AP) is usually devoid of systemic side
      effects: few reports of hypo- or hyperglycaemia have been published. Our study
      aimed to assess the influence on glucose homeostasis and insulin secretion of
      long-term exposure to AP used for prophylaxis of Pneumocystis carinii pneumonia
      in HIV-positive patients, and to compare the impact on insulin secretion of AP,
      whether administered for the first time or after prolonged monthly exposure.
      DESIGN: Retrospective cross-sectional controlled study (main objective) and non
      randomized prospective controlled study. PATIENTS: We compared glucose
      homeostasis and C peptide response to 1 mg intravenous glucagon in patients who
      had previously inhaled > or = 10 prophylactic aerosols (group 1, n = 21) and in
      HIV-positive controls (groups 2 and 3, n = 28) who had received none. Both groups
      were comparable for age and body-mass index, but CD4 T-lymphocyte counts and
      Karnofsky scores were both significantly higher in the control group. RESULTS:
      Fasting (T0) blood glucose, fructosamine and response to the first glucagon test
      were similar in both groups, but postprandial glucose, glycated haemoglobin and
      fasting C peptide were significantly higher (P < 0.05) in the pentamidine group.
      A second glucagon test was performed on the same day, 3 h (T3) after AP
      inhalation in 35 patients (in 21 after > or = 10 aerosols, group 1; in 14 after
      the first, group 2) and in 14 HIV-positive controls (group 3). The only
      significant difference between the three groups in C peptide response to this
      second test was a lower peak T3/peak T0 ratio in group 1. Plasma amylase and
      creatinine were not altered by the aerosol. CONCLUSION: Long-term prophylactic
      exposure to AP had minor but significant effects on glucose homeostasis and
      insulin secretion but did not modify pancreatic and renal function. The
      detrimental effects induced by long-term exposure to AP found in our study are
      probably not clinically relevant, but a more prolonged exposure to AP might
      conceivably induce more severe alterations.

PMID- 7576326
TI  - HIV infection and invasive cervical carcinoma in an Italian population: the need
      for closer screening programmes in seropositive patients.
AB  - OBJECTIVE: To evaluate in an Italian population the prevalence, characteristics
      at first diagnosis and outcome of HIV-seropositive individuals with cervical
      carcinoma referred to a tertiary-care institution. DESIGN: A retrospective
      evaluation of all patients referred for invasive cervical carcinoma from 1991 to
      1994. SETTING: The departments of obstetrics and gynaecology, and radiotherapy at
      San Gerardo Hospital, University of Milan, Italy. PATIENTS: A total of 340 women
      were treated over a 3-year period (186 aged < 50 years). Six patients were found
      to be HIV-seropositive. INTERVENTIONS: Seropositive patients were treated
      according to current institutional protocols, irrespective of HIV status. Four
      underwent radiotherapy and two radical hysterectomy as primary treatment.
      RESULTS: Although five HIV-seropositive patients were known to be infected 13-81
      months before diagnosis of cervical cancer, none had received a PAP smear in the
      last year and only one in the last 2 years. HIV patients were younger than
      general population (P = 0.02), with a significant history of intravenous drug use
      (P = 0.000001) and with more advanced disease (P = 0.04). Two HIV-positive
      patients also received polychemotherapy (one adjuvant and one salvage treatment)
      and both completed the planned treatment. Within 24 months two patients had died
      of cancer and one of AIDS; one is alive with AIDS and cancer and two are free of
      disease. CONCLUSIONS: This study confirms that in a southern European population,
      HIV-seropositive women present to tertiary-care institutions with more advanced
      disease and have a poorer prognosis than the general population. Strict screening
      programs for cervical dysplasia and cancer are warranted for HIV-seropositive
      patients.

PMID- 7576327
TI  - The incidence of complications after caesarean section in 156 HIV-positive women.
AB  - OBJECTIVE: To investigate the risks of post-operative complications in HIV
      positive mothers who undergo a caesarean section (CS) because the delivery cannot
      be safely accomplished by the vaginal route or to protect the infant from viral
      infection. DESIGN: In a multicentre study, we reviewed the incidence and type of
      post-operative complications in 156 HIV-positive women who underwent a CS. These
      results were compared with those observed in an equal number of HIV-uninfected
      women who matched for the indication requiring a caesarean delivery, the stage of
      labour, the integrity or rupture of membranes, and the use of antibiotic
      prophylaxis. SETTING: Seven teaching hospitals providing obstetrical care for
      mothers infected with HIV. RESULTS: We found that six HIV-infected mothers
      suffered a major complication (two cases of pneumonia, one pleural effusion, two
      severe anaemia and one sepsis) compared with only one HIV-negative woman who
      required blood transfusion after surgery. Minor complications like post-operative
      fever, endometritis, wound and urinary tract infections were significantly more
      frequent in HIV-positive women than controls. Multivariate analysis revealed that
      in HIV-infected women the only factor associated with a significant increase in
      the rate of complications was a CD4 lymphocyte count < 200 x 10(6)/l.
      CONCLUSIONS: The results of our study indicate that HIV-positive mothers are at
      an increased risk of post-operative complications when delivered by CS. The risk
      of post-operative complications is higher in HIV-infected women who are severely
      immunodepressed.

PMID- 7576331
TI  - Use of pooling and outpatient laboratory specimens in an anonymous seroprevalence
      survey of HIV infection in British Columbia, Canada.
AB  - OBJECTIVE: To conduct an anonymous HIV seroprevalence survey to establish a
      baseline estimate of HIV seroprevalence in a general population; to evaluate
      serum pooling and alternative testing strategies as cost-saving measures. DESIGN:
      Prospective anonymous HIV seroprevalence study using outpatient laboratory
      specimens. SETTING: Two large non-hospital-associated outpatient chemistry
      testing laboratories in the major population centers in British Columbia, Canada.
      PATIENTS AND SERA: Leftover sera received for chemistry screen testing in
      outpatient laboratories were provided to the study after chemistry testing was
      completed. Those from patients aged < 15 and > or = 55 years were excluded.
      METHODS: Patient identifiers were erased from samples. Sera were pooled 10:1 and
      tested by viral lysate enzyme-linked immunosorbent assay (ELISA). Sera from HIV
      positive pools were tested individually. All individual HIV-positive specimens
      were retested for verification of positivity using a recombinant protein ELISA.
      MAIN OUTCOME MEASURES: HIV seroprevalence rates were stratified by sex, age
      group, and geographic area; and costs of pooling and alternative algorithm
      strategy were compared with those of conventional methods. RESULTS: A total of
      80,238 sera were collected from 66,658 individuals (53% women, 47% men). Of
      these, 276 men (88.3 per 10,000) and 24 women (6.8 per 10,000) were HIV
      seropositive. The highest rates were in those aged 30-34 years, for both men and
      women. Using pooling and non-Western blot verification saved US$2.07 per
      specimen, or 80% of the cost for conventional testing. CONCLUSIONS: The anonymous
      outpatient laboratory setting is practicable to obtain a reasonable estimate of
      HIV seroprevalence rates in a general population. Such studies can be made cost
      effective by pooling sera and using alternative confirmatory strategies.

PMID- 7576329
TI  - A community trial of the impact of improved sexually transmitted disease
      treatment on the HIV epidemic in rural Tanzania: 2. Baseline survey results.
AB  - OBJECTIVES: To determine baseline HIV prevalence in a trial of improved sexually
      transmitted disease (STD) treatment, and to investigate risk factors for HIV. To
      assess comparability of intervention and comparison communities with respect to
      HIV/STD prevalence and risk factors. To assess adequacy of sample size. SETTING:
      Twelve communities in Mwanza Region, Tanzania: one matched pair of roadside
      communities, four pairs of rural communities, and one pair of island communities.
      One community from each pair was randomly allocated to receive the STD
      intervention following the baseline survey. METHODS: Approximately 1000 adults
      aged 15-54 years were randomly sampled from each community. Subjects were
      interviewed, and HIV and syphilis serology performed. Men with a positive
      leucocyte esterase dipstick test on urine, or reporting a current STD, were
      tested for urethral infections. RESULTS: A total of 12,534 adults were enrolled.
      Baseline HIV prevalences were 7.7% (roadside), 3.8% (rural) and 1.8% (islands).
      Associations were observed with marital status, injections, education, travel,
      history of STD and syphilis serology. Prevalence was higher in circumcised men,
      but not significantly after adjusting for confounders. Intervention and
      comparison communities were similar in the prevalence of HIV (3.8 versus 4.4%),
      active syphilis (8.7 versus 8.2%), and most recorded risk factors. Within-pair
      variability in HIV prevalence was close to the value assumed for sample size
      calculations. CONCLUSIONS: The trial cohort was successfully established.
      Comparability of intervention and comparison communities at baseline was
      confirmed for most factors. Matching appears to have achieved a trial of adequate
      sample size. The apparent lack of a protective effect of male circumcision
      contrasts with other studies in Africa.

PMID- 7576328
TI  - A community trial of the impact of improved sexually transmitted disease
      treatment on the HIV epidemic in rural Tanzania: 1. Design.
AB  - OBJECTIVE: To describe the rationale and design of a randomized trial of the
      impact of improved services for the treatment of sexually transmitted diseases
      (STD) on the incidence of HIV infection in Mwanza Region, Tanzania. METHODS: The
      likely impact of improved STD treatment services on HIV incidence, and the need
      for empirical information on the effectiveness of this intervention strategy, are
      discussed. The rationale and design of such an intervention programme in Mwanza
      Region, and of a community-randomized trial to measure the impact of the
      programme on HIV and other STD, are presented. Problems in the design and
      interpretation of the trial are reviewed. RESULTS: Results of the baseline survey
      of the cohort of over 12,000 adults in 12 communities are presented in a
      companion paper. CONCLUSION: There is an urgent need for effective preventive
      measures against the HIV epidemic in sub-Saharan Africa and other developing
      regions. Improved STD treatment has been promoted as a potentially effective
      strategy, but there is little empirical information on its impact. The trial in
      Mwanza Region is the first randomized study of this intervention and should
      provide valuable data for health policy makers.

PMID- 7576330
TI  - Couple communication, sexual coercion and HIV risk reduction in Kigali, Rwanda.
AB  - OBJECTIVE: To describe sexual interaction and HIV-related communication in
      Rwandan couples and to examine their relationship to HIV testing and condom use.
      STUDY DESIGN: Cross-sectional survey of a longitudinal cohort. METHODS: In 1988,
      women recruited for an epidemiological study of HIV, and interested male
      partners, received confidential HIV testing and counseling. Two years after
      enrollment, 876 women reporting one steady partner in the past year completed a
      questionnaire addressing sexual and HIV-related communication, sexual motivation
      and violence in the partnership. RESULTS: Men control sexual decision making, and
      coercive sex and violence between partners is not uncommon. HIV-positive women
      were more likely to report coercive sex and less likely to have discussed their
      test results with their partner. Women with HIV-positive partners were more
      likely to report being physically abused. Condom use was more common if the man
      had been previously tested, and if women reported discussing or negotiating
      condom use. HIV-negative women with untested or seronegative partners were the
      least likely to use condoms or to discuss or attempt to negotiate condom use.
      CONCLUSIONS: Participation of the male partner is crucial for successful HIV risk
      reduction in couples. HIV testing and counseling of couples has beneficial long
      term effects on condom use and HIV-related communication. Couple communication is
      associated with condom use, but only when the discussion is specific (sexually
      transmitted disease risks and using condoms). Seronegative women with untested
      partners are at increased risk for HIV as they are the least likely to discuss or
      attempt to negotiate condom use.

PMID- 7576332
TI  - HIV status of female sex partners of men reactive to HIV-1, HIV-2 or both viruses
      in Abidjan, Cote d'Ivoire.
AB  - OBJECTIVES: To compare rates of serologic concordance in the female sex partners
      of men with HIV-1 and HIV-2 infections, and to determine the serologic status of
      sex partners of men who reacted serologically to both viruses. DESIGN: Cross
      sectional study. SETTING: Infectious diseases service in a University Hospital in
      Abidjan, Cote d'Ivoire (West Africa). PARTICIPANTS: Hospitalized men reactive on
      synthetic peptide-based tests to HIV-1, HIV-2 or both viruses (dually reactive),
      and their spouses visiting them in hospital. OUTCOME MEASURES: Serologic status
      of female spouses of seropositive men. RESULTS: The serologic status of 540
      spouses of 490 HIV-1- and/or HIV-2-positive, hospitalized men was studied.
      Similar proportions of spouses of HIV-1-infected men (49%) and HIV-2-infected men
      (44%) were concordantly seropositive. The overall prevalence of infection in
      spouses of dually reactive men (72%) was significantly higher than in spouses of
      other men; 44% of these spouses were infected with HIV-1, 8% with HIV-2, and 20%
      were themselves dually reactive. Considering only the seropositive female spouses
      of men monotypically reactive to HIV-1 or HIV-2, and the male spouses of women
      monotypically infected, rates of serologic discordance were significantly greater
      in men (24%) than women (7%). CONCLUSIONS: Men were likely to have been infected
      earlier than women because of their HIV-associated illness; also, men more
      frequently had serologic profiles indicative of infection outside of the union.
      Rates of serologic concordance in spouses of men with advanced HIV-1 or HIV-2
      infection were similar (44-49%). Dually reactive hospitalized men frequently
      (72%) had seropositive sex partners, most of whom were HIV-1-positive. Dual
      reactivity was also frequent in these spouses, suggesting transmission of both
      HIV-1 and HIV-2, or of a cross-reactive strain, and a minority of partners were
      infected with HIV-2 alone. Prospective studies of discordant couples using
      quantitative molecular diagnostic techniques are required for better
      understanding of dual reactivity and transmission of HIV-1 and HIV-2.

PMID- 7576333
TI  - Dual seroreactivity to HIV-1 and HIV-2 in female sex workers in Abidjan, Cote
      d'Ivoire.
AB  - OBJECTIVE: To determine the absolute and proportional prevalence of dual
      seroreactivity to HIV-1 and HIV-2 in female sex workers in Abidjan, to determine
      risk determinants for this serologic profile, and to describe the associated
      clinical and immunological characteristics. DESIGN: Cross-sectional study.
      SETTING: Confidential clinic for female sex workers in Abidjan. PARTICIPANTS:
      Female sex workers. MAIN OUTCOME MEASURES: HIV serostatus, CD4+ counts, women
      with AIDS, behavioural and sociodemographic characteristics. RESULTS: Among 1209
      women tested, the overall HIV seroprevalence was 80%, while the prevalence of
      dual seroreactivity was 30%. Dual seroreactivity accounted for 38% of all HIV
      infections. Compared with women reacting to HIV-1 only, dually seroreactive women
      were significantly more likely to have been in sex work for a longer period, to
      be aged > or = 20 years, and to charge less money for intercourse. No difference
      in mean CD4+ count was noted between women with dual seroreactivity (561 x
      10(6)/l) and HIV-1-seropositive women (558 x 10(6)/l). CONCLUSIONS: Female sex
      workers in Abidjan had the highest absolute (30%) and proportional rate (38%) of
      dual seroreactivity yet described in any population. Increased sexual exposure is
      associated with an increased risk of dual seroreactivity. Although better
      molecular diagnostic techniques are required, a substantial proportion of female
      sex workers in Abidjan is likely to be infected with both HIV-1 and HIV-2.

PMID- 7576335
TI  - Decreasing prevalence hides a high HIV incidence: Miami.
AB  - OBJECTIVE: Study methods of assessing HIV trends in sexually transmitted disease
      (STD) clinics where blinded seroprevalence has been among the highest in the
      United States. DESIGN: Cross-sectional and retrospective cohort. METHODS:
      Reviewed computerized records of the four Miami STD clinics for 1987-1992.
      RESULTS: A total of 53,403 persons had 70,793 tests. When testing began, 13% were
      HIV-positive. By 1992, 35% of all tests were performed on previously HIV-negative
      persons. This caused a faster decline in overall seroprevalence (to 7%) compared
      with seroprevalence among persons tested for the first time (to 9%). The
      percentage of tests performed for previously HIV-negative persons varied among
      age, race and sex subgroups, causing confounding if overall seroprevalence was
      used to compare groups. Seroconversion occurred in 514 patients. Black women were
      most likely to be positive on retesting (4.3%). Incidence rates did not change
      much over time, remaining at 2.5% per year. CONCLUSIONS: When using a routine HIV
      testing data to analyze trends, separate analyses should be undertaken for
      patients who were (or were not) previously tested. In these patients, the
      prevalence decreased slightly but incidence remained high, particularly among
      black women.

PMID- 7576334
TI  - HIV risk behaviors but absence of infection among drug users in detoxification
      centers outside Yunnan province, China, 1993.
AB  - OBJECTIVES: To date, HIV spread in China has occurred principally among injecting
      drug users (IDU) in remote border regions of Yunnan province. We therefore sought
      to better understand the risks for and prevalence of HIV infection among drug
      users in parts of China outside Yunnan province. METHODS: A behavioral survey of
      drug use and AIDS-related knowledge was conducted among all consenting drug users
      who entered treatment from 1 November to 31 December 1993 in seven provincial
      drug detoxification centers outside Yunnan province. After giving verbal informed
      consent, all drug users were tested for HIV. RESULTS: Of the 1293 study
      participants, 207 (16%) reported injecting drugs. The proportion of IDU among all
      drug users varied widely by region, from 1% in Sha'anxi and Gansu provinces in
      the northwest region to 58% in Guangxi province in the south. IDU were more
      likely than non-IDU to be single and unemployed or self-employed, but did not
      differ in other demographic aspects. Among all drug users, 2% reported sharing
      needles without cleaning equipment, while 5% shared with some cleaning. Although
      1060 (82%) drug users had heard of AIDS and most knew about its sexual (79%),
      parenteral (77%), and perinatal (60%) modes of transmission, many had
      misconceptions about its spread by casual contact. Of the 207 IDU tested for HIV,
      none were HIV-positive (95% confidence interval, 0--1.4). CONCLUSION: The absence
      of HIV infections detected in this study suggests that the prevalence of HIV is
      currently low among IDU in China outside the Yunnan province. However, the
      behavior of these IDU puts them at high risk for HIV infection. Prevention
      efforts are needed to prevent the spread of HIV among IDU throughout China and to
      avoid the experience of neighboring countries in Asia.

PMID- 7576336
TI  - HIV transmission and Kaposi's sarcoma among European women.
AB  - OBJECTIVE: To assess the association between the presence of Kaposi's sarcoma
      (KS) as an AIDS-defining illness and HIV transmission categories among European
      women with AIDS. DESIGN: Comparison of the prevalence of KS as an AIDS-defining
      illness in different HIV transmission categories. METHODS: Odds ratios (OR) and
      95% confidence intervals (CI) for KS were computed by means of unconditional
      multiple logistic regression equations. RESULTS: KS was reported in 344 (2.2%)
      out of 15,809 women diagnosed with AIDS. Women who reported HIV infection via
      heterosexual intercourse had a > twofold increase of KS risk than intravenous
      drug users (OR, 2.4; 95% CI, 1.9-3.0). Particularly elevated OR were observed
      among women originating from African or Caribbean countries (OR, 4.9; 95% CI, 3.7
      -6.5), and in partners of bisexual men (OR, 4.8; 95% CI, 2.8--8.2). Such risk
      patterns for KS were consistent in different countries, age groups and year of
      AIDS diagnosis. CONCLUSIONS: These results are in agreement with similar analyses
      from the United States, and support the existence of some putative KS agent(s)
      which can be acquired via sexual intercourse with bisexual men, or earlier in
      life in countries where non-AIDS-associated KS is frequent.

PMID- 7576337
TI  - Microsporidiosis in patients with relatively preserved CD4 counts.

PMID- 7576338
TI  - First case of osteomyelitis due to Phialophora richardsiae in a patient with HIV
      infection.

PMID- 7576339
TI  - Plasma HIV-1 load and nosocomial transmission in Romanian children.

PMID- 7576340
TI  - HIV-1 group O sensitivity to antiretroviral drugs.

PMID- 7576341
TI  - Production of nitric oxide from peripheral blood mononuclear cells and
      polymorphonuclear leukocytes of patients with HIV-1.

PMID- 7576342
TI  - Endophthalmitis as a complication of intravitreal treatment for cytomegalovirus
      retinitis.

PMID- 7576343
TI  - Comment from the World Bank.

PMID- 7576345
TI  - New statements on the Gaia theory.
AB  - Gaia is the name the ancient Greeks gave to their goddess of the Earth and is the
      root of words like geography and geology. Gaia is also a straightforward
      scientific theory about the Earth and the organisms that inhabit it. Gaia theory
      is testable and has a proper mathematical basis in a set of closely coupled
      differential equations. We do not yet know if it is a good explanation of the way
      our planet works; the evidence is only partially gathered. Its main value at this
      stage is to provide a different way to look at the Earth. In science, Gaia theory
      has already led to significant discoveries but just as important it forces us to
      question whether the good of humankind is the only thing that matters. The true
      value of the journeys into space was to reveal the Earth as a live planet. They
      made us realise for the first time that humanism is not enough. The view from
      space teaches that we are part of a greater entity, the Earth, and that our
      survival and its good health are inextricably entwined. Perhaps in time we can
      expand our view to encompass the larger systems of the galaxy and the Universe.
      Now the Earth needs our full attention.

PMID- 7576344
TI  - [50 years of the Spanish Microbiology Society].

PMID- 7576346
TI  - Understanding the causes of aging and cancer.
AB  - Cancer, a disease typical of old age, is in large part of degenerative origin.
      Several factors leading to the development of cancer and other degenerative
      diseases are discussed. The results of cancer tests in animals have been
      misinterpreted; they are mainly carried out by using synthetic chemicals, whereas
      most carcinogenic substances are natural chemicals. Animals have defense systems
      which prevent them from the carcinogenic effects of both natural and synthetic
      chemicals.

PMID- 7576347
TI  - Formation and microbial utilization of amorphous aggregates in the sea:
      ecological significance.
AB  - Amorphous organic particles, ("marine snow"), are thought to play a vital role in
      the transfer of carbon and energy from the euphotic layers of the ocean to the
      deep sea bed. These particles are mainly derived from phytoplankton extracellular
      release. As 10 to 40% of the dissolved organic carbon consists of colloidal
      material, colloids may represent a prominent role in these transfer processes.
      These colloids adsorb charged molecules efficiently and can coagulate further to
      form the recently described transparent exopolymer particles and eventually the
      ubiquitous macroscopic marine snow. The other mechanism proposed leading
      ultimately to marine snow formation is inefficient top-down control of
      phytoplankton growth by zooplankton. In the senesce of the phytoplankton bloom
      the cell surface becomes sticky due to the release of polysaccharides, and single
      phytoplankton cells then aggregate. Subsequently these aggregates become densely
      colonized by auto- and heterotrophic microbes, but while the abundance of these
      microorganisms is from 2 to 4 orders of magnitude higher than in the ambient
      water, their growth rates are usually not significantly increased in the
      aggregates. In this review, the reasons for this conspicuous pattern are
      discussed and recently investigated novel types of particles and their
      significance in the light of oceanic carbon transfer are presented.

PMID- 7576348
TI  - Analysis of bacterial genomes by pulsed field gel electrophoresis.
AB  - The present article reviews the main achievements reached in bacterial genetics
      through the application of pulsed field gel electrophoresis. In particular, it
      summarizes the main subjects where the use of this technique has significant
      relevance for the analysis of bacterial genomes. With this purpose, it sums up
      some of the most relevant examples which illustrate the applicability of this
      technique in bacterial taxonomy, in epidemiological work and in the study of
      bacterial genome organization (including the assessment of the number of genomic
      elements and the size and topology of all of them). This technique, which makes
      it possible to make genomic comparisons in an easy, fast and repetitive way, has
      been demonstrated to be especially useful for those bacteria where the
      application of classical genetic techniques has not been possible.

PMID- 7576349
TI  - Effect of cultivation conditions on glycerophosphate oxidase production by a
      mutant strain of Aerococcus viridans.
AB  - The effect of different concentrations of carbon source (lactose) and inducer
      (glycerol) on biomass and glycerophosphate oxidase (GPO) production by mutant
      strain of Aerococcus viridans 1509 was tested. The best combination of lactose
      and glycerol concentrations for good enzyme productivity was 0.5% lactose and
      2.5% glycerol. Further improvement of GPO levels was achieved after scaling-up of
      the bioprocess and cultivation of the cells in a 3 liter laboratory bioreactor.
      Using 4.5 x 10(-5) m3 s-1 air flow rate during growth, GPO activity increased 20
      times in comparison with cultivation in flasks.

PMID- 7576350
TI  - Detection of Bacillus larvae spores in Argentinian honeys by using a semi
      selective medium.
AB  - A semi-selective medium for the detection in Argentinian honeys of spores of
      Bacillus larvae, a pathogen of American foulbrood, was developed. The technique
      involves dilution of samples (1:2) in phosphate buffer, concentration of spores
      by centrifugation and heat treatment prior to inoculation. Two media (JNxPa and
      JNxPb) were prepared from J-agar, to which nalidixic acid and pipemidic acid were
      added. Both JNxP media were reliable for the isolation of B. larvae colonies and,
      at the same time, prevented the development of other Bacillus species which
      normally develop on the plates before B. larvae spores can germinate.

PMID- 7576352
TI  - [Brief history of the Spanish Microbiology Society, I. From 1946 to 1971].

PMID- 7576351
TI  - Photosynthetic oxidation of MnS and FeS by Chlorobium spp.
AB  - The ability of two species of green phototrophic sulfur bacteria (Chlorobium
      limicola and Chlorobium phaeobacteroides) to photosynthetically oxidize several
      metal sulfides (MnS, FeS, NiS, CuS, ZnS, CdS and PbS) by has been tested in
      laboratory batch cultures. Both species only oxidized MnS and FeS, which are the
      ones having higher solubilities (pKs = 13.5 and 18.1, respectively). The specific
      oxidation rates were directly related to the solubility of the metal sulfide
      involved. C. limicola oxidized MnS and FeS at specific rates of 11.8 and 0.9
      mumol S2-h-1 mg protein-1, respectively. Specific oxidation rates of C.
      phaeobacteroides for MnS and FeS were 7.1 and 1.8 mumol S2-h-1 mg protein-1,
      respectively. The oxidation of both metal sulfides resulted in the release of the
      free-soluble metal ions in the culture media, but no toxic effect of these
      cations on the photosynthetic activity of the cells was observed. The anaerobic
      photosynthetical oxidation of MnS and FeS by Chlorobium reveals an adaptation of
      this bacterial species to sulfide-poor environments, and introduces a new process
      in the Mn, Fe, and S biogeochemical cycles to be considered.

PMID- 7576353
TI  - Plasmid transfer during growth and survival of Escherichia coli.

PMID- 7576354
TI  - Regulation mechanisms of the gene expression involved in ciliate cryptobiosis.

PMID- 7576355
TI  - Protein kinases and phosphatases during the developmental cycle of myxobacteria.

PMID- 7576356
TI  - Intraspecific diversity in Bacteria. The case of Escherichia coli.

PMID- 7576357
TI  - Genetic bases of the chromosomal polymorphism of industrial yeasts.

PMID- 7576358
TI  - The yeast Phaffia rhodozyma as an industrial source of astaxanthin.

PMID- 7576359
TI  - Survival strategies of enteric bacteria in aquatic systems.

PMID- 7576361
TI  - Bacterial survival mechanisms in microbial mats.

PMID- 7576360
TI  - The survival of enteric viruses in the water environment.

PMID- 7576362
TI  - Ciliated populations in activated sludge plants: structure, dynamic and indicator
      value.

PMID- 7576363
TI  - Molecular identification of pathogenic actinomycetes: a new approach.

PMID- 7576364
TI  - 4,5-Dihydrobenzo[a]pyrene-4,5-trans-(e,e)-diol.
AB  - The title compound, C20H14O2, is a metabolite of the chemical carcinogen
      benzo[a]pyrene. The crystal structure consists of groups of molecules in each of
      which both hydroxy groups donate and accept hydrogen bonds. Stacking of
      dihydrobenzo[a]pyrene ring systems occurs along the crystallographic c axis.

PMID- 7576365
TI  - [Mn6O2[O2C-3,5-(NO2)2-C6H3]10-(C5H5N)2[(CH3)2CO]2].2(CH3)2CO.- 2(C2H5)2O and
      [Mn6O2(O2CC6H5)10-(NCCH3)4].
AB  - The structures of di(acetone)tetrakis(mu 3,5-dinitrobenzoato-kappa 2 O:kappa
      O')hexakis(mu-3,5-dinitrobenzoato-kappa O:kappa O')-di-mu 4-oxo
      di(pyridine)tetramanganese(II)dimanganese (III)-acetone-diethyl ether (1/2/2),
      (1), and tetrakis(acetonitrile)tetrakis(mu 3-benzoato-kappa 2 O:kappa
      O')hexakis(mu-benzoato-kappa O:kappa O')-di-mu 4-oxo
      tetramanganese(II)dimanganese(III), (2), are reported. Both compounds contain six
      octahedrally coordinated Mn centres, arranged as two MnII2MnIII2 (mu 4-O)
      tetrahedra sharing the MnIII-MnIII edge.

PMID- 7576366
TI  - Diaqua(5,10,15,20-tetraphenylporphinato)iron(III) Perchlorate,
      [Fe(C44H28N4)(H2O)2]ClO4.
AB  - The crystal structure of a new crystal form of [Fe(TPP)(H2O)2]ClO4 has been
      determined. The asymmetric unit contains one molecule in a general position and a
      half molecule with required inversion symmetry. The two independent molecules
      have almost identical average values for the equatorial Fe-Np bond lengths [2.029
      (4) and 2.028 (6) A], and the axial Fe-O bond lengths are 2.140 (2) and 2.121 (3)
      A for molecule 1 (in a general position) and 2.126 (2) A for molecule 2 (in a
      special position). A brief comparison of the core structure and hydrogen-bonding
      environment of this molecule with two other crystal forms is described.

PMID- 7576367
TI  - Construction of the tetracyclic skeleton of leucothol A.
      1,2,4a,5,6,7,8,9,10,10a,11,11a-dodecahydro-11-hydroxy-11-methyl-7-
      phenylthiomethyl-5aH-5a,8-methano-cyclohepta[b] naphthalen-10-one.
AB  - The title compound, C24H30O2S, is a tetracyclic intermediate for the synthesis of
      leucothol A and the first example of an ethanoanthracene skeleton to be
      synthetized. The single-crystal X-ray structure of this compound is presented.

PMID- 7576368
TI  - An intermediate for chloroquine analogs: (E)-2-(4,7-dichloro-2-quinolinyl)-3
      (dimethylamino)-2-propenal.
AB  - The title compound C14H12C12N2O, has been shown to have an E configuration about
      the double bond in the propenal moiety. Significant delocalization of the lone
      pair on the N atom of the dimethylamino group into the pi system of this moiety
      is indicated by the planarity about this N atom.

PMID- 7576369
TI  - 2',3'-Dideoxy-3'-C,2'-N-[(3R,5R)-5-ethoxy-carbonyl-2-methyl-1, 2-isoxazolidine]
      ribothymidine.
AB  - The title compound, C15H21N3O7, is a thymidine derivative with a
      tetrahydroisoxazole (THI) ring fused to the sugar ring at the 2'- and 3'-C atoms.
      The thymine base is in an anti conformation [chi = -122.5 (3) degrees] while the
      ribose moiety has C2'-exo,C3'-endo (3T2) conformation with a highly flattened
      sugar ring [P = -5.8, tau m = 13.1 degrees]. The molecule contains a pseudo
      twofold axis on the C2'-C3' bond with the ethyl ester group acting as the base
      and the N-methyl group acting as the 5'-hydroxyl group in a nucleoside. The THI
      ring fused to the furanose has a C3'-endo,C4'-exo (3T4) conformation [P = 4.18,
      tau m = 19.3 degrees]. The ethyl ester moiety is disordered with respect to two
      conformations, the population of the major form being 87.4 (8)% and that of the
      minor form 12.6 (8)%.

PMID- 7576371
TI  - 2,6,6-Trimethyl-2-oxo-1,3-dioxa-6-azonia-2-phosphocyclooctane iodide.
AB  - The eight-membered ring in the title compound, C7H17NO3P+.I-, has a boat-chair
      conformation, with the local mirror plane passing through the cyclic O atom and
      methylene C atom adjacent to the N atom. The P = O bond is pseudo-axial and the P
      CH3 bond is pseudo-equatorial. The P-N distance is 3.821 (2) A.

PMID- 7576370
TI  - 4-(Acetylamino)-3-hydroxy-5-nitrobenzoic acid.
AB  - The 4-(acetylamino)-3-hydroxy-5-nitrobenzoic acid molecule, C9H8N2O6, a designed
      inhibitor for the influenza virus neuraminidase protein, crystallizes as hydrogen
      bonded dimers. The dihedral angles of the substituent groups with respect to the
      planar phenyl moiety are 5.0 (3) degrees for the carboxyl group, 45.0 (2) degrees
      for the nitro group and 37.3 (1) degrees for the acetylamino substituent. The
      crystal structure is stabilized by intermolecular hydrogen bonding.

PMID- 7576373
TI  - Computational studies of crystalline H3PO4.
AB  - A polarized split-valence wavefunction was computed for the H3PO4 molecule at its
      neutron crystallographic valence geometry, and the wavefunction was used to map
      the molecular electron-density distribution and to simulate X-ray crystal
      structure factors for both static, at-rest and dynamic thermally averaged
      structures. The thermal vibrational averaging was approximated using anisotropic
      mean-square atomic displacements from approximately 300 K neutron diffraction
      data. The simulated X-ray data were used to test pseudoatom multipole modeling of
      the valence electron-density distribution, in particular, radial modeling of the
      M valence shell of the P atom, and deconvolution of the nonspherical density
      features from anisotropic vibrational smearing.

PMID- 7576372
TI  - 3,4-di-O-acetyl-2,5-anhydro-1,6-di-O-(p-tolylsulfonyl)-D-mannitol.
AB  - The title compound, 2,5-bis(4-methylphenylsulfonyloxy-methyl)oxolane-3,4-diyl
      diacetate, C24H28O11S2, lies on a crystallographic twofold axis. It adopts a
      perfect twist 3(4)T conformation in the solid state. The puckering parameters of
      the tetrahydrofuran ring are q = 0.32 (8) A and rho = 92.3 (5) degrees. The
      acetyl groups are planar, with the non-H atoms deviating less than 0.002 (3) A
      from their mean plane. They have an (S)-cis conformation with the C-O and C = O
      bonds eclipsed, and each acetyl group is orientated with the C = O group
      syndiaxial to the C-H bond at the ring C atom to which the group is attached.

PMID- 7576374
TI  - Experimental electron density in crystalline H3PO4.
AB  - X-ray diffraction data for H3PO4 crystals have been measured to dmin = 0.46 A
      resolution, and used to model the electron-density distribution with the hydrogen
      structure of the crystals adopted from an earlier neutron diffraction analysis.
      The molecule is asymmetric in the crystal with site symmetry 1 (C1), but the
      local symmetries of the pseudoatomic densities are, within experimental error,
      equivalent as they would be under idealized 3m (C3v) molecular symmetry. Although
      the experimental analysis entailed substantial problems with absorption and
      extinction corrections, the static deformation density from the experiment agrees
      very well with that from a polarized split-valence molecular orbital wavefunction
      for an isolated molecule with the crystallographic molecular geometry. Hydrogen
      bonding in the crystal polarizes the molecule's P==O acceptor group towards P(+)-
      O-, and appears to relocalize the lone-pair density of the P--OH donor groups.
      Crystal data: anhydrous orthophosphoric acid, H3PO4, M(r) = 98.00, room
      temperature, P2(1)/c, a = 5.7572 (13), b = 4.8310 (17), c = 11.5743 (21) A, beta
      = 95.274 (12) degrees, V = 320.55 (25) A3, Z = 4, dx = 2.030 mg mm-3, mu = 0.660
      mm-1 for lambda(Mo K alpha) = 0.7107 A, F(000) = 200 e-, R(parallel F) = 0.026
      for 3512 unique reflections.

PMID- 7576376
TI  - Electrostatic potentials from charge-density studies of benzamide at 123 K.

PMID- 7576375
TI  - On the differences between X-ray and neutron thermal vibration parameters.
AB  - For crystal structures analyzed by both X-ray and neutron diffraction, the
      anisotropic mean-square displacement parameters of the non-H atoms are sometimes
      found to differ significantly. The differences can usually be adjusted by either:
      (1) an isotropic factor q, defined by UijX = qUijN, to correct for a temperature
      difference between the two experiments; (2) anisotropic factors qij, defined by
      UijX = qijUijN, to correct for a temperature difference and different anisotropic
      diffraction effects of absorption, extinction, thermal diffuse scattering,
      multiple reflection, or systematic measuring errors in the two experiments; (3)
      anisotropic diffraction correction terms delta Uij, defined by UijX = UijN +
      delta Uij; (4) the sum of an isotropic temperature correction and anisotropic
      diffraction corrections, defined by UijX = qUijN + delta Uij. Correction
      parameters q, qij and delta Uij are easily calculated by linear least-squares
      fit, and the corrections from (3) or (4) seem to be the most reliable.
      Corrections calculated from X-ray and neutron Uij's of the non-H atoms of a
      crystal can be useful for adjusting the neutron Uij's of the H atoms for
      adoption, along with the neutron coordinates of the H atoms, as fixed parameters
      in an X-ray analysis of the electron density distribution.

PMID- 7576377
TI  - Holographic methods in X-ray crystallography. IV. A fast algorithm and its
      application to macromolecular crystallography.
AB  - The holographic method makes use of partially modeled electron density and
      experimentally measured structure-factor amplitudes to recover electron density
      corresponding to the unmodeled part of a crystal structure. This paper describes
      a fast algorithm that makes it possible to apply the holographic method to
      sizable crystallographic problems. The algorithm uses positivity constraints on
      the electron density and can incorporate a 'target' electron density, making it
      similar to solvent flattening. The potential for applying the holographic method
      to macromolecular X-ray crystallography is assessed using both synthetic and
      experimental data.

PMID- 7576378
TI  - Solution of the phase problem in crystallography and application to dynamical
      electron diffraction.
AB  - Unitarity, a fundamental principle of scattering theory, leads to the prediction
      of an essentially unique set of phases for the scattering amplitude from a
      complete knowledge of the differential cross section or, in the case of a
      crystal, from the diffracted intensities. The Sayre equation and all the direct
      methods of phasing following there from are derived as a special case of
      unitarity for zero excitation error. Dynamical and kinematical scattering are
      considered, and the relationship between them, S = exp(i tau nzK), is obtained.
      Applications to the case of electron diffraction including for non-zero
      excitation error are discussed.

PMID- 7576380
TI  - Effect of acid etchant composition and etch duration on enamel loss and resin
      composite bonding.
AB  - PURPOSE: To investigate the effects of different acid etchants' ability to
      condition enamel as gently as possible to remove a minimum of substance only, to
      produce a highly retentive pattern, and finally to ensure frosty appearance of
      the etched enamel for clinical control of the procedure. MATERIALS AND METHODS:
      Two commercial uni-etch gels, Gluma 2000-1 and Scotchbond Multi-Purpose Etchant,
      were studied together with gels of 5, 10, 20 and 35% phosphoric acid and varying
      amounts of thickening agents in the 20% gel. Enamel loss was measured with a
      contact-free method by materials and etch duration, and the shortest etching
      times for dull frosty enamel appearance were determined. Shear bond strength
      (SBS) was measured after 24 hours' storage in water. RESULTS: Enamel loss was
      very low with the commercial agents and increased with H3PO4 concentrations and
      with etch duration. While the commercial compounds produced no frosty enamel even
      after 120-second etch duration, the phosphoric acids produced frosted enamel
      after 15, 30, 60 and 120-second application of 35, 20, 10 and 5% acids,
      respectively. All etchants and etch durations tested produced effective retentive
      patterns. No differences in SBS were noted, and the failure modes were
      consistently cohesive in resin.

PMID- 7576379
TI  - Wear resistance of dual-cured resin luting agents.
AB  - PURPOSE: To evaluate the three-body wear resistance of five commercially
      available dual-cured resin-based composite luting agents compared both in a dry
      state and after water storage. MATERIALS AND METHODS: Six specimens of each
      material were prepared and tested for three-body wear resistance in the ACTA wear
      machine for 250,000 cycles and the loss of material was measured with a
      profilometer. Material wear was measured under three conditions: dry storage, 6
      month water storage, and 12-month water storage. RESULTS: One-way and two-way
      ANOVA and Tukey's HSD test of multiple comparisons revealed significant
      differences in wear resistance. Water storage did not significantly affect the
      wear resistance of four of the five materials. The order of wear resistance was:
      Cosmedent Insure > Vivadent Dual-Cement > Kerr Porcelite Dual Cure >
      Jeneric/Pentron Optec Luting Cement > Chameleon Mirage FLC (P < or = 0.0001). The
      rank order of wear resistance could not be readily predicted when based solely on
      the manufacturers' reported physical specification data.

PMID- 7576382
TI  - Effect of particle variation on wear rates of posterior composites.
AB  - PURPOSE: To evaluate the relationship between filler size, shape, mechanical
      properties and wear resistance of posterior resin composite was evaluated.
      MATERIALS AND METHODS: Six UDMA/TEGDMA-based experimental resin composites
      consisting of different types of filler particles were investigated. These
      included four sized spherical fillers, (9.88 microns, 2.01 microns, 0.62 micron,
      0.20 micron) and two irregular, (9.46 microns, 1.97 microns). Property
      measurements consisted of hardness and compressive strength. Wear resistance was
      evaluated by a three-bodied in vitro wear test. RESULTS: The composites
      containing the smallest sized spherical particle exhibited maximum mechanical
      strength and maximum wear resistance. The composites containing the largest
      spherical particle exhibited minimum wear resistance. There were no significant
      differences amongst those containing similar sized fillers regardless of particle
      shape. However, differences between the 0.20 microns spherical filled composite
      and other composites were statistically significant. SEM analysis showed that
      only the larger sized filler exhibited some exfoliation after wear testing. The
      smaller size spherical filler exhibited better mechanical strength and
      substantially higher wear resistance.

PMID- 7576383
TI  - Color stability of light-cured and post-cured composites.
AB  - PURPOSE: To determine the color stability of five composites after light-curing
      and recommended post-curing using reflection spectrophotometry. MATERIALS AND
      METHODS: Samples of the composites were prepared as disks 10 mm in diameter and 1
      mm thick. The pre-cured samples were prepared with a clear plastic sheet on the
      top and bottom of disk, pressed between two glass slabs to the thickness of the
      mold, and then removed from between the glass slabs. The color of the samples was
      measured with the clear plastic sheets in place. The color of the composites
      before curing served as the control. RESULTS: Light-curing caused barely
      perceptible to perceptible color changes for all of the composites from the pre
      cured shade. Clearfil and TrueVitality changed color significantly more than
      Charisma, Conquest C&B and Herculite XRV. Once the composites were light-cured,
      post-curing caused no further perceptible changes in shade.

PMID- 7576381
TI  - Effect of Gluma desensitization on dentin bond strength.
AB  - PURPOSE: To determine whether the use of Gluma as a desensitizing agent on tooth
      preparations has any effect upon the bond strength of a resin composite
      restoration cemented to dentin. MATERIALS AND METHODS: Forty extracted human
      molars which were caries and restoration-free were occlusally reduced to remove
      enamel. Twenty of the teeth received a Gluma desensitization treatment and 20
      were untreated (controls). Following a 7-day storage period, simulated resin
      composite inlays were bonded to all of the dentin specimens, using either All
      Bond 2 with All-Bond Crown & Bridge Cement or OptiBond with Porcelite Dual Cure.
      Twenty-four hours later, the shear bond strength of the specimens was determined.
      RESULTS: Statistical analysis (paired t-tests) indicated no significant
      difference in bond strength for Gluma-treated specimens when compared to
      controls, for either bonding material.

PMID- 7576384
TI  - Effect of glass ionomer manipulation on early fluoride release.
AB  - PURPOSE: To determine the amount of fluoride released from several glass ionomer
      products [Fuji Cap II, Fuji Ionomer Type II, Ketac-Silver, Chelon-Silver, and
      Miracle Mix (hand-mixed and encapsulated)], and to compare them between
      triturated (5, 10, 15 seconds) encapsulated and hand-mixed glass ionomers.
      MATERIALS AND METHODS: The amount of fluoride released at 1, 2, 3, 7, 14, 21 and
      28 days after the start of immersion in deionized-distilled water at 37 degrees C
      was determined with a fluoride ion selective electrode. Rates of fluoride release
      and cumulative amounts of fluoride release were calculated. RESULTS: Each glass
      ionomer released the greatest amount of fluoride during the first 24-hour period.
      Although there was some variation between products, generally the hand-mixed
      specimens released significantly (P < 0.05) less fluoride than those prepared by
      mechanical trituration (10 and 15 seconds). The cumulative amounts of fluoride
      released from the mechanically triturated glass ionomers were significantly (P <
      0.05) greater than the amounts released from the hand-mixed glass ionomers. No
      significant differences in the cumulative amounts of fluoride released from
      triturated materials were found among the different trituration times.

PMID- 7576385
TI  - Dentin surface treatments and glass ionomer microleakage.
AB  - PURPOSE: To investigate the effect of various dentin treatments on the
      microleakage of Class V restorations restored with a resin-modified glass ionomer
      restorative cement. MATERIALS AND METHODS: Forty extracted noncarious molar teeth
      received Class V preparations with the occlusal margin in enamel and the gingival
      margin in dentin. Preparations were restored with Fuji II LC glass ionomer
      restorative material. Five dentin treatments were tested prior to restoration (n
      = 16): Group 1: without dentin pretreatment; Group 2: with GC Dentin Conditioner
      (10% polyacrylic acid solution); Group 3: with ProBond Dentin Primer; Group 4:
      with GC Dentin Conditioner and ProBond Dentin Primer; Group 5: with ProBond
      Dentin Primer followed by application of ProBond adhesive. Samples were
      thermocycled, stained with 0.5% basic fuchsin, and sectioned to evaluate
      microleakage. Data was analyzed using Kruskal-Wallis and Wilcoxon Signed-Rank
      Tests at a significance level of P < 0.05. SEM analysis was performed on selected
      samples to examine the dentin/glass ionomer interface. RESULTS: There was no
      statistically significant difference between any of the dentin pretreatments with
      regard to enamel or dentin microleakage. SEM analysis indicated excellent
      adaptation between glass ionomer and dentin for all treatment groups.

PMID- 7576386
TI  - Microleakage of dentin-amalgam bonding agents.
AB  - PURPOSE: To evaluate in vitro the microleakage of various dentin bond/resin liner
      systems when used with both a spherical and an admixture alloy. MATERIALS AND
      METHODS: Class V cavity preparations were prepared on 60 noncarious extracted
      human molar teeth with one margin in enamel and another in dentin and restored
      with either Dispersalloy or Tytin alloy. Treatment groups utilizing either no
      liner, Copalite varnish, Amalgambond Plus/HPA, Tenure with Panavia EX Dental
      Adhesive, Syntac with Dual Cem, and All-Bond 2 with Liner F were tested. Samples
      were thermocycled, stained, and sectioned to evaluate microleakage. RESULTS: A
      significant reduction in microleakage at the enamel and dentin margins was found
      in all dentin bond system/resin liner groups when compared to unlined and
      Copalite-lined alloys. There were no significant differences in total
      microleakage scores between the alloy types. Statistically significant
      differences in microleakage were detected between some systems. The Tenure with
      Panavia EX treatment group exhibited a significantly lower total microleakage
      when used with Tytin. The Syntac/Dual Cem treatment groups exhibited a
      significantly higher total microleakage when used with Dispersalloy.

PMID- 7576387
TI  - Bond strengths of glass ionomers using a dentin adhesive.
AB  - PURPOSE: To determine the effect of All-Bond 2 adhesive on the shear bond
      strengths to dentin of Fuji II LC, Photac-Fil, and Vitremer. MATERIALS AND
      METHODS: The occlusal surfaces of 60 extracted human third molars were ground
      flat to expose dentin and were polished to 600 grit. The teeth were randomly
      assigned to six groups (n = 10). In three groups, dentin was treated using the
      conditioner or primer recommended by the manufacturer. In the remaining groups,
      dentin was treated with All-Bond 2 etchant, primer, and adhesive. Restorative
      materials were applied to the treated surfaces in gelatin capsule matrices and
      were light-cured. Specimens were thermocycled, and shear bond strengths were
      determined using a materials testing machine. RESULTS: The use of All-Bond 2
      improved the mean bond strength of Photac-Fil from 1.7 to 8.7 MPa, but decreased
      the bond strength of Vitremer from 7.3 to 5.5 MPa. The bond strengths of Fuji II
      LC were 7.5 and 7.9 MPa, with and without the use of All-Bond 2, respectively.
      ANOVA and Duncan's multiple range test showed that only the difference for Photac
      Fil was statistically significant.

PMID- 7576388
TI  - Bonding of resin composites to resin-modified glass ionomers.
AB  - PURPOSE: To evaluate the bonding between resin composites and resin-modified
      glass ionomer restorative materials. MATERIALS AND METHODS: Bar-shaped specimens
      of Fuji II LC, Photac-Fil, and Vitremer were fabricated in a mold. After
      application of unfilled resin, resin composite (either Silux Plus or Restorative
      Z100) was condensed into the mold against the glass ionomer substrate and was
      light-cured. These bonded specimens, as well as intact specimens of each
      material, were placed on a three-point bending apparatus and were loaded until
      failure using a Zwick testing machine. The transverse strength of each specimen
      was calculated. RESULTS: Mean transverse strengths of bonded specimens ranged
      from 50% to 78% of the transverse strength of the intact glass ionomer materials.
      The lowest transverse strength was 18.1 MPa, for Photac-Fil/Z100, and the highest
      was 29.6 MPa, for Fuji II LC/Silux. Statistical analysis indicated that the type
      of composite used had no significant effect on transverse strength. However, the
      type of resin-modified glass ionomer used was significant. Although there was
      much overlap between materials, bonded specimens made with Fuji II LC had the
      highest absolute strength, and those made with Photac-Fil had the lowest absolute
      strength. Bonded Vitremer specimens had the highest transverse strength relative
      to the cohesive strength of the material.

PMID- 7576389
TI  - Anticalculus efficacy of three dentifrices.
AB  - PURPOSE: To evaluate the anticalculus effect of three commercial dentifrices.
      MATERIALS AND METHODS: A 12-week independent and double-blind clinical study was
      conducted on a population of calculus-forming adult male and female subjects in
      Budapest, Hungary to directly compare the anticalculus efficacy of three
      commercially-available dentifrices, as compared to a placebo dentifrice. The
      three commercially-available anticalculus dentifrices compared in this clinical
      study to a 0.243% sodium fluoride/silica placebo dentifrice were as follows: (1)
      A dentifrice containing 1.3% soluble pyrophosphate and 1.5% of a PVM/MA copolymer
      in a 0.243% sodium fluoride/silica base. (2) A dentifrice containing 0.3%
      triclosan and 2% of a PVM/MA copolymer in a 0.243% sodium fluoride/silica base.
      (3) A dentifrice containing 0.3% triclosan and 0.75% zinc citrate in a 1.14%
      sodium monofluorophosphate/silica base. RESULTS: All three anticalculus
      dentifrices provided statistically significant reductions in supragingival
      calculus formation, as compared to a placebo dentifrice, after 12 weeks of use.
      The reductions in supragingival calculus formation ranged from 39% to 55%, as
      compared to a placebo dentifrice, for the three commercially-available
      anticalculus dentifrices. There was no statistically significant difference among
      the three commercially-available dentifrices with regard to anticalculus
      efficacy.

PMID- 7576390
TI  - Effect of aqueous solutions of sucralose on plaque pH.
AB  - PURPOSE: To compare the effect on in vivo plaque pH of rinsing with an aqueous
      solution of sucralose (alone or in combination with maltodextrin or maltodextrin
      and dextrose) to the effect of rinsing with an aqueous solution of sucrose.
      MATERIALS AND METHODS: Each solution (four in total) had a sweetness equivalent
      to two teaspoons of sucrose in 6 oz. of water. The four test solutions were
      administered randomly over four test visits (one solution per visit) to 10
      subjects presenting 2-day resting plaque. Before, and at specified time intervals
      over 60 minutes following the rinse, in vivo plaque pH was monitored at six
      designated sites using a Beckman 3500 digital pH meter. Data were analyzed by
      ANOVA. RESULTS: The mean pH minimum for the sucralose rinse (6.56) was
      significantly higher than the sucralose/maltodextrin (SM),
      sucralose/maltodextrin/dextrose (SMD), and sucrose rinses (6.15, 5.84, and 5.29,
      respectively). The mean delta pH (difference between resting and minimum pH) for
      the sucralose rinse (0.45) was significantly lower when compared to the SM
      (0.79), SMD (1.14), and sucrose (1.69) rinses. The differences seen in mean pH
      minimum and mean delta pH for the SM and SMD groups vs. the sucrose group were
      also statistically significant. Mean areas under the pH vs. time curve for the
      sucralose, SM and SMD rinses were all significantly less compared to the sucrose
      rinse. Rinsing with aqueous solutions of sucralose, or of sucralose in
      combination with maltodextrin and/or dextrose (commercially available
      formulations, of sucralose) was less acidogenic than rinsing with a sucrose
      solution of equivalent sweetness.

PMID- 7576391
TI  - Resin-dentin interface of Scotchbond Multi-Purpose dentin adhesive.
AB  - PURPOSE: To evaluate the interface between dentin, Scotchbond Multi-Purpose
      (SMP), and resin composite (Z100) using confocal fluorescence microscopy.
      MATERIALS AND METHODS: Novel techniques were employed to view and record at video
      rate the application of the SMP primer and adhesive onto the dentin surface. The
      subsurface morphology of the dentin/restorative interface was also studied. To
      facilitate this study, the components of the adhesive system were labeled with
      fluorescent dyes. RESULTS: In an ideal situation, the primer and adhesive
      penetrated the dentin tubules, a distinct hybrid zone was formed and a thin layer
      of adhesive was observed at the interfacial region. However, the primed dentin
      surface was sensitive to disruption by the adhesive application brush during its
      placement, so that parts of the primer layer could be incorporated into the
      adhesive. This disruption could only be seen using confocal microscopy and a
      fluorescence labeling technique. Delamination of the primer layer was not
      observed when the adhesive film was thinned by air blowing. The application of an
      air stream to the cavity surface increased the penetration of the primer and
      adhesive along the dentin tubules, but also increased the thickness of the
      adhesive within irregularities on the cavity surface and at the cavity line
      angle. The cause of the problems in the handling properties of SMP may be the
      difference in viscosity between the two components (primer and adhesive) at the
      adhesive interface.

PMID- 7576392
TI  - De/remineralization from sodium fluoride dentifrices.
AB  - PURPOSE: To test the demineralization/remineralization effects of sodium fluoride
      dentifrices using an in situ single-section crown model system. MATERIALS AND
      METHODS: A fluoride dose response was evaluated using 0, 1100 and 2800 ppm F-,
      along with the effects of an enhanced fluoride delivery system (polyampholyte
      NaF). The single-section crown model was employed with supervised toothbrushing
      twice a day. At the end of each 1-month study leg, sections were removed and
      replaced with new sections for the next leg. Both before and after the double
      blind, crossover portion of the study, sections were evaluated by polarized light
      microscopy and microradiography. The change in mineral content of the enamel and
      root lesions was analyzed by ANOVA with a Waller-Duncan K-Ratio Test post hoc.
      RESULTS: The placebo dentifrice group showed a loss of mineral and was
      statistically different from all groups. The fluoride dentifrices showed
      increasing amounts of enamel mineral gain, with increasing fluoride
      concentration. The polyampholyte-NaF delivery system with 1100 ppm F- was
      equivalent to the 2800 ppm F- dentifrice. Root lesions gave similar rank-order
      results although all treatments showed demineralization or mineral loss.

PMID- 7576393
TI  - Disparate circadian variations of blood pressure and body temperature in
      bedridden elderly patients with cerebral atrophy.
AB  - Twenty bedridden elderly patients with normal sleep-wake cycles were studied to
      evaluate the circadian variations of blood pressure, pulse rate, body core
      temperature, cortisol, and catecholamines with a focus on their relation to
      cerebral atrophy. Twenty-four-hour blood pressure (BP) and pulse rate monitorings
      were done with simultaneous measurement of urinary bladder temperature. Urine was
      also collected every 4 h to measure 17-hydroxycorticosterone and catecholamines.
      Based on the brain CT, frontal horn index (FHI: maximal distance between
      bilateral frontal horns/the corresponding width of the skull) was calculated as
      an index of cerebral atrophy. Analysis by the cosinor method revealed that the
      significant circadian rhythm with nocturnal decline was observed in only 9
      patients (45%) for BP and in 13 patients (65%) for pulse rate. In contrast, 19 of
      20 patients (95%) showed significant circadian rhythms of bladder temperature,
      with the nadirs appearing between 00:06 and 06:54. In the subgroup of mild
      cerebral atrophy (FHI < 0.30, n = 11), BP and pulse rate fell modestly but
      significantly during nighttime, whereas they did not fall in the subgroup of
      moderate to severe cerebral atrophy (FHI > or = 0.30, n = 9). The possibility
      could not be excluded that the sleep disturbance might result in the relatively
      high BP during nighttime. Bladder temperature, 17-hydroxycorticosteroids, and
      catecholamines showed significant nocturnal falls in both groups. In conclusion,
      nocturnal fall of BP disappeared in the bedridden elderly patients with cerebral
      atrophy, which cannot be explained by the change in the circadian variation of
      the sympathetic nervous system, cortisol, or body core temperature.

PMID- 7576394
TI  - Autonomic function in type I diabetes mellitus complicated by nephropathy. A
      cross-sectional analysis in the presymptomatic phase.
AB  - The purpose of this study was to determine the prevalence of parasympathetic and
      sympathetic autonomic dysfunction in long-standing type I diabetics with
      established nephropathy and to correlate autonomic function with cardiac risk
      factors. We used prospective analysis of heart rate variations to standardized
      testing and 24-hour blood pressure control prior to enrollment in a study
      utilizing various methods of intense diabetic control to prevent deterioration of
      kidney function. The settings were outpatient clinical research units. The
      patients were 42 type I diabetics with proteinuria (total urinary protein > or =
      300 mg/day or urinary albumin > or = 100 mg/day) and creatinine clearance > or =
      30 mL/min. Heart rate variation during respiratory cycles with change in posture
      from supine to upright, and during the Valsalva maneuver was recorded by a
      computerized method. Mean arterial blood pressure was recorded for 24 h by a
      computerized method. Heart rate variations in this group were abnormal during
      timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in
      15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%)
      whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial
      pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men
      than in women (1.00 v 1.06, P < or = .05). Absence of deep tendon reflexes was
      associated with an increased incidence of both parasympathetic (respiratory rate
      variation) and sympathetic (postural rate variation) abnormalities (both P < or =
      .05). Loss of vibration sensation was not associated with autonomic functional
      abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576395
TI  - White coat hypertension and white coat effect. Similarities and differences.
AB  - The rise in blood pressure (BP) associated with clinical visit (white coat
      effect) may be one basic mechanism of white coat hypertension (persistently
      raised clinic BP together with a normal BP outside the clinic), but the relations
      between white coat hypertension, white coat effect, and target organ damage have
      not yet been assessed on large populations. Thus, we performed 24-h noninvasive
      ambulatory BP monitoring and 2D-guided M-mode echocardiography in 1,333 untreated
      subjects with essential hypertension and 178 control normotensive subjects. White
      coat hypertension was defined by an average daytime ambulatory BP < 131/86 mm Hg
      in women and < 136/87 mm Hg in men and its prevalence was 18.9% (n = 252). The
      white coat effect was calculated for systolic and diastolic BP as the difference
      between clinic BP and average daytime ambulatory BP. Echocardiographic left
      ventricular mass was slightly but not significantly greater in the group with
      white coat hypertension than in the normotensive group (93 v 87 g/m2, P = NS),
      and increased in the group with ambulatory hypertension (112 g/m2, P < .01). The
      prevalence of white coat hypertension markedly decreased from the first to the
      fourth Joint National Committee V (JNC V) stage of severity of hypertension
      (186/559 subjects (33%) in I; 59/501 (11%) in II; 7/230 (3%) in III; 0/43 (0%) in
      IV; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576396
TI  - Systemic hemodynamics and renal function during brain natriuretic peptide
      infusion in patients with essential hypertension.
AB  - We assessed the cardiovascular and renal effects of human brain natriuretic
      peptide (BNP) infused at a dose inducing an increase in plasma BNP to
      pathophysiologic levels, in eight hypertensive patients in a randomized, placebo
      controlled, cross-over study. Left ventricular performance, cardiac output
      (echocardiography), heart rate, arterial pressure, glomerular filtration rate
      (GFR; creatinine clearance), sodium excretion, intrarenal sodium handling
      (lithium clearance method), and urine flow rate were measured in the infusion and
      postinfusion periods (1 h each), together with plasma BNP and the urinary
      excretion rate of cGMP. Plasma BNP levels increased from 2.90 +/- 0.74 to 36.43
      +/- 5.51 pmol/L (P < .01) at the end of the infusion and were still elevated at
      the end of the postinfusion period (7.03 +/- 1.41 pmol/L, P < .05). The urinary
      excretion of cGMP was also significantly higher during BNP infusion. Left
      ventricular performance, cardiac output, arterial pressure, and peripheral
      vascular resistance were not affected by BNP. Peptide infusion induced a
      significant increase in GFR (placebo, 115 +/- 24; BNP, 147 +/- 19 mL/min), sodium
      excretion (placebo, 129 +/- 40; BNP, 243 +/- 60 mumol/min), and urine flow rate.
      All these effects were observed also in the postinfusion period. The natriuretic
      effect of BNP was attributable to both an increase in filtered sodium load and a
      reduction of distal sodium reabsorption. These results suggest that BNP may
      contribute to maintain renal function and sodium excretion in patients with
      essential hypertension.

PMID- 7576397
TI  - Quinapril reduces microalbuminuria in essential hypertensive and in diabetic
      hypertensive subjects.
AB  - To investigate the metabolic and renal effects of the nonsulfhydryl, tissue
      active ACE inhibitor quinapril in diabetes and in hypertension, we studied 30
      essential hypertensives and 24 non-insulin-dependent (type II) diabetic (NIDDM)
      subjects with hypertension. Systolic and diastolic blood pressures, plasma
      glucose, and insulin responses to an oral glucose load (75 g), lipid profile, and
      urinary albumin excretion were evaluated before and after 8 weeks' administration
      of quinapril (10 to 40 mg/day). Quinapril produced a significant and comparable
      reduction of arterial blood pressure in both groups. Mean arterial pressure
      decreased from 114.8 +/- 0.9 to 94.2 +/- 1.1 (-17.9 +/- 1.5%) in the essential
      hypertensive group and from 118.4 +/- 1.6 to 96.2 +/- 1.4 (-18.4 +/- 1.6%) in the
      diabetic hypertensive group. In both essential hypertensives and diabetic
      hypertensive subjects with microalbuminuria, quinapril significantly and
      comparably reduced the urinary albumin excretion rate (UAE); UAE decreased from
      32.5 +/- 5.5 micrograms/min to 14.7 +/- 3.7 micrograms/min (P < .05 v baseline)
      in the diabetic-hypertensive group and from 27.5 +/- 3.0 micrograms/min to 11.6
      +/- 2.7 micrograms/min (P < .05 v baseline) in the essential hypertensives.
      Altogether, a direct correlation was found between the initial level of UAE and
      the UAE reduction after quinapril (delta UAE) (r = 0.706, p < .05). Insulin and
      glucose responses to an oral glucose tolerance test and the lipid profiles were
      not modified by quinapril treatment. The results confirm that quinapril is an
      effective antihypertensive agent that additionally reduces microalbuminuria in
      both hypertensive diabetics and in patients with essential hypertension, without
      altering insulin sensitivity and lipid profiles.

PMID- 7576398
TI  - Quinapril decreases myocardial accumulation of extracellular matrix components in
      spontaneously hypertensive rats.
AB  - In genetic and acquired hypertension, a structural remodeling of the nonmyocyte
      compartment of myocardium, including the accumulation of fibrillar collagen and
      other components of the extracellular matrix (ECM) within the interstitium,
      represents a determinant of pathologic hypertrophy that leads to ventricular
      dysfunction. Therefore, to evaluate the potential benefit of the angiotensin
      converting enzyme (ACE) inhibitor quinapril in reversing the interstitial
      remodeling in spontaneously hypertensive rats (SHR) with established left
      ventricular hypertrophy (LVH), we treated 16-week-old male SHR with oral
      quinapril (average dose, 10 mg/kg body weight/day) for 20 weeks. Interstitial
      fibrosis was determined morphometrically using an automatic image analyzer. The
      amount of collagen was evaluated by measuring myocardial hydroxyproline
      concentration. Myocardial deposition of collagen molecules (types I, III, and IV)
      and other ECM components (fibronectin, laminin) was analyzed by
      immunohistochemical techniques using specific monoclonal antibodies. The activity
      of ACE was measured in left ventricular tissue by a fluorometric assay. In
      quinapril-treated SHR compared with 36-week-old untreated SHR and age- and sex
      matched Wistar-Kyoto (WKY) controls, we found 1) a lesser degree of LVH and a
      lesser level of blood pressure, 2) a lesser degree of interstitial fibrosis,
      represented by less interstitial collagen volume fraction (5.73 +/- 0.45% v 3.42
      +/- 0.28%, P < .05; WKY, 3.44 +/- 0.66%), 3) a lower hydroxyproline concentration
      (1.09 +/- 0.05 mumol/L/g dry weight/100 g body weight to 0.81 +/- 0.05 mumol/L/g
      dry weight/100 g body weight, P < .05; WKY, 0.96 +/- 0.06 mumol/L/g dry
      weight/100 g body weight), 4) a lesser presence of collagen fibers, and 5) a
      lesser presence of collagen IV, fibronectin, and laminin.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7576399
TI  - Glucocorticoid-induced hypertension in the elderly. Relation to serum calcium and
      family history of essential hypertension.
AB  - To explore the syndrome of glucocorticoid-induced hypertension in the elderly, we
      analyzed the clinical findings from 35 patients aged more than 65 years (12 men,
      23 women) who received glucocorticoid therapy. Resting blood pressures (BP) were
      less than 140/90 mm Hg before glucocorticoid therapy, and patients were
      apparently disease-free apart from the condition for which glucocorticoid therapy
      was prescribed. Glucocorticoid-induced hypertension is defined as systolic BP
      more than 160 mm Hg and/or diastolic BP more than 95 mm Hg after glucocorticoid
      administration. Glucocorticoid-induced hypertension was seen in 13 patients
      (37.1%); all patients with hypertension [steroid (glucocorticoid)-induced
      hypertension (SH(+)) group] received more than 20 mg of prednisolone daily, and
      BP rose rapidly within a week of commencing glucocorticoid administration. The
      SH(+) group did not differ significantly in terms of age, heart rate, blood
      count, plasma biochemistry, plasma renin activity, plasma aldosterone, routine
      urinalysis, or urinary electrolytes from patients who did not show hypertension
      [SH(-) group]. However, serum total calcium concentrations were significantly
      lower in the SH(+) group both before and after 2 weeks of glucocorticoid therapy
      than in the SH(-) group. Furthermore, the SH(+) group showed a significantly
      higher percentage of patients with a positive family history of essential
      hypertension than the SH(-) group. In conclusion, although the detailed
      mechanisms are as yet uncertain, glucocorticoid-induced hypertension occurs often
      in elderly patients, and is more common in patients with total serum calcium
      concentrations lower than the normal range, and/or in those with positive family
      history of essential hypertension.

PMID- 7576400
TI  - Age is a major determinant of the divergent blood pressure responses to varying
      salt intake in essential hypertension.
AB  - Blood pressure responses to 1 week of low (20 mmol sodium/day) and high (300 mmol
      sodium/day) salt intake were investigated in a double-blind, randomized study in
      46 white, nonobese subjects with essential hypertension (13 women, 33 men; mean
      age 45.3 +/- 2.2 years, age range 25 to 80 years). The individuals were
      classified as salt-sensitive when mean arterial blood pressure rose by at least 5
      mm Hg during high salt intake, as salt-resistant when mean arterial blood
      pressure changed by less than 5 mm Hg, and as "counter-regulators" when mean
      arterial blood pressure fell by at least 5 mm Hg during the high salt diet. Mean
      arterial blood pressure of all subjects taken together increased from 101.9 +/-
      1.4 mm Hg during salt restriction to 103.7 +/- 1.5 mm Hg (P < .05) during salt
      loading. Eleven subjects (23.9%) were classified as salt-sensitive, 27 (58.7%) as
      salt-resistant, and 8 (17.4%) as counter-regulators. Multiple regression analysis
      revealed that age, but not baseline blood pressure, sex, body mass index, or
      family history of hypertension contributed significantly to the change in blood
      pressure following the diets. Ten of the 11 salt-sensitive subjects were older
      than the median age of 45 years. In salt-sensitive, as compared to salt
      resistant, hypertensive subjects, creatinine clearance was lower and plasma renin
      activity was suppressed at baseline as well as during low and high salt intake.
      In contrast, plasma concentrations of norepinephrine and atrial natriuretic
      peptide were elevated in salt-sensitive subjects. These differences between the
      groups appeared, at least partially, to be age-related.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7576401
TI  - Left ventricular diastolic function in hypertensive patients with unstable angina
      and single coronary artery disease.
AB  - The present study was performed to investigate left ventricular diastolic (LVD)
      function in hypertensive patients with unstable angina. Three groups of 17
      patients each were studied. Group 1 consisted of hypertensives with unstable
      angina (HTU); group 2, normotensives with unstable angina (NTU); and group 3,
      untreated, uncomplicated hypertensives (HT). The LVD function was assessed
      echocardiographically by transmitral valve Doppler flow to measure the ratio
      between the early diastolic filling (E) and the atrial contraction phase (A). An
      E/A ratio of < 1 was suggestive of LVD dysfunction. Left ventricular mass (LVM),
      from an M-mode echocardiogram using the Penn-Cube formula, was corrected to body
      surface area (LVM/S) using a standard nomogram. Data are represented as median
      values and analyzed by Mann-Whitney test. P was significant at < .05. The HTU
      group had an E/A ratio of 0.8, and the NTU and HT groups had ratios of 1.17 and
      1.1, respectively. There was significant diastolic dysfunction in the HTU group
      compared with the NTU and HT groups (P = .037 and .049, respectively). Although
      the LVM/S was significantly higher in the HTU group when compared with the HT
      group (110.6 and 96.9, respectively, P = .017), there was no significant
      difference between the HTU and NTU groups (123.1), P = .67. Hypertensive patients
      with unstable angina have significant LVD dysfunction that seems to be
      independent of LVM and ischemia. This may be attributable to increased stiffness
      of the left ventricle or structural left ventricular abnormalities.

PMID- 7576402
TI  - Alterations of cytosolic calcium in platelets and erythrocytes of Lyon
      hypertensive rats.
AB  - Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH
      (pHi) (including their responses to thrombin), as well as erythrocyte [Ca2+]i and
      45Ca2+ influx, were studied in Lyon hypertensive (LH) and normotensive (LN) rats
      aged 3 months. Platelets of LH rats were characterized by substantially elevated
      basal [Ca2+]i values, higher [Ca2+]i levels after thrombin stimulation, and
      enhanced initial rate of thrombin-induced Mn2+ entry through receptor-operated
      Ca2+ channels. Basal platelet pHi values were not significantly different in LH
      and LN animals but thrombin elicited a significant alkalinization only in LH
      platelets. Erythrocytes of LH rats had an enhanced initial rate of 45Ca2+ and
      tended to elevated [Ca2+]i levels. Our data indicate profound alterations in cell
      Ca2+ handling in platelets and erythrocytes of LH rats, similar to those
      previously described in spontaneously hypertensive rats of the Okamoto-Aoki
      strain. The analysis of the relations between blood pressure, plasma lipids, and
      cell Ca2+ handling suggested that triglycerides, but not cholesterol, might be
      involved in altered platelet Ca2+ handling in LH rats.

PMID- 7576403
TI  - Alpha 1-adrenergic receptors in cardiac ventricles of Dahl rats.
AB  - This study was designed to examine the effects of sex, age, and a high-salt diet
      on cardiac alpha 1-adrenoceptors in an animal model of genetic hypertension, the
      Dahl salt-sensitive rat. Ventricular alpha 1-adrenoceptors were measured by
      radioligand binding with [3H]prazosin in membrane fractions in Dahl S and R rats
      of 7, 12, and 15 weeks of age. In both S and R rats, the maximal binding (Bmax)
      of alpha 1-adrenoceptor binding was greater in male than in female rats. The Bmax
      decreased with age in both the S and R strains; at 12 weeks of age, Bmax was
      approximately one-half of that observed at 7 weeks of age in both S and R
      strains. In the rats fed a high-salt diet, the Bmax tended to be greater in S
      rats than in R rats at 12 weeks of age and this difference became significant at
      15 weeks of age. A significant positive correlation was found between the Bmax
      and the heart-to-body weight ratio in the Dahl S and R rats. The dissociation
      constant (Kd) was not different between male S and R rats at each age. These
      results suggest that the ventricular alpha 1-adrenoceptor may be involved in
      cardiac hypertrophy in Dahl rats.

PMID- 7576404
TI  - Association between salt sensitivity and insulin concentrations in patients with
      hypertension.
AB  - This study was performed in 28 patients with mild to moderate hypertension,
      classified as being either salt sensitive or salt resistant on the basis of the
      percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily
      salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent
      decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance
      was defined as a percent decrease in MAP of < 3% and eight patients satisfied
      this criterion. Both plasma glucose and insulin concentrations following a 75-g
      oral glucose challenge were significantly higher after the high-salt diet in the
      salt-sensitive patients. Furthermore, there were correlations of marginal
      statistical significance between the decrease in MAP after the low-salt diet and
      the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses
      to oral glucose. These data are consistent with the view that there is an
      association between resistance to insulin-mediated glucose disposal and salt
      sensitivity in patients with high blood pressure.

PMID- 7576405
TI  - N-acetylcysteine potentiates the antihypertensive effect of angiotensin
      converting enzyme inhibitors.

PMID- 7576406
TI  - Accuracy and performance of the Terumo ES-H51, a new portable blood pressure
      monitor.

PMID- 7576407
TI  - The selling of pain.

PMID- 7576408
TI  - A reassessment of center-of-mass dynamics as a determinate of the metabolic
      inefficiency of above-knee amputee ambulation.
AB  - Above-knee (AK) amputation substantially increases the metabolic cost of
      ambulation. Although the biomechanical mechanisms contributing to the increase
      have not been well studied, it has been assumed that altered center-of-mass (COM)
      kinematics and increased mechanical work account for the adverse effect on oxygen
      consumption. To understand better the relationship between mechanical work and
      the metabolic cost, 8 normal subjects and 8 traumatic AK amputees were studied
      during overground ambulation. Using segmental energy and inverse dynamics
      analyses, trunk COM excursion, the mechanical work associated with movement of
      the COM, and the work done by the major lower limb sagittal plane muscle groups
      were determined. Oxygen consumption was measured using the Douglas bag technique.
      The metabolic cost was 27% higher in amputees compared with normal subjects (P >
      0.01), but no significant differences were noted in the excursion of or the work
      done on the trunk COM. The muscle work needed to complete a stride was
      significantly greater in normal subjects compared with amputees. These results
      indicate that the role of abnormal kinematics and their effect on the mechanical
      work of walking are complex and incompletely understood, but may be
      overemphasized as a cause of the increased metabolic cost. Alternative mechanisms
      for the metabolic inefficiency must be considered.

PMID- 7576409
TI  - Gut hormone release in patients after spinal cord injury.
AB  - Gastrointestinal disorders including abdominal pain, abdominal distention, ileus,
      and constipation are common after spinal cord injury. In physiologic studies of
      patients with spinal cord injury, slow gastric emptying, ileal dilation, and
      abnormal rectosigmoid motility have been found. However, it is not yet known
      whether abnormal gut hormone release is important in the development of these
      abnormalities. In healthy volunteers, there are postprandial increases in plasma
      peptide YY and motilin levels, which appear related to neural mechanisms. We
      hypothesized that abdominal sympathetic pathways provide tonic inhibition of
      peptide YY and motilin release and that postprandial increases in these gut
      hormones are mediated through spinal pathways. Fasting serum was obtained from
      normal volunteers, paraplegic patients, and tetraplegic patients. In studies in
      which patients were fed, serum was obtained from normal volunteers, paraplegic
      patients, and tetraplegic patients before and at 30-min intervals after a 280
      kcal meal. Serum motilin and peptide YY levels were measured by
      radioimmunoassays. In fasting studies, there was a trend (P = 0.23) toward
      increased fasting serum motilin in paraplegic patients, and this result did not
      support tonic inhibition of motilin release. Fasting peptide YY levels were not
      increased in spinal cord injury patients, which did not support tonic inhibition
      of peptide YY release. In fed studies, there were strong trends toward
      postprandial increases in serum peptide YY in volunteers and paraplegic patients
      and a significant postprandial rise in serum peptide YY in tetraplegic patients
      (P = 0.04). This was evidence against involvement of spinal pathways in
      postprandial release of peptide YY.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576411
TI  - Long-term effects of strokes on bone mass.
AB  - The purpose of the study was to determine the long-term effects of muscle
      weakness secondary to strokes on the bone mineral content of the hemiparetic
      limb. Patients who had experienced single recent strokes were studied. The bone
      mineral content of each limb was measured by Dual Energy X-ray Absorptiometry
      using the region of interest analysis program. Muscle strength of each muscle
      group was ranked using the Oxford scale, and the mean was calculated for each
      limb. Bone and muscle parameters were measured within seven days after the stroke
      and repeated thereafter at monthly intervals for up to 6 mo. A repeated measures
      analysis of variance, Newman-Keuls pair-wise comparisons, and orthogonal
      contrasts were done for each parameter. Significance levels were set at P < 0.05.
      Sixteen patients were included in this study. Demineralization was more
      pronounced in the upper than lower limbs. Demineralization of bones on the
      paralyzed side started during the first month after the stroke and gradually
      progressed. By the fourth month, the bone mineral content decreased by a mean of
      9.3% (P = 0.01) and 3.7% (P = 0.01) in the upper and lower limbs, respectively,
      for the 11 patients followed for 4 mo. In the patients we followed for more than
      4 mo, there was no further significant mineral loss. No change in bone mineral
      content was observed in the healthy nonparetic limbs. In conclusion, after a
      stroke, bone demineralization occurs in the paralyzed side and reaches its
      maximum within 3 to 4 mo. Arms are affected more than legs.

PMID- 7576410
TI  - A management trial for Duchenne cardiomyopathy.
AB  - The physiatrist can now be instrumental in prolonging the survival of individuals
      with neuromuscular disease by using respiratory muscle aids. As a result,
      morbidity and mortality from cardiomyopathy are likely to increase for patients
      with generalized myopathies. One hundred consecutive patients with dystrophin
      deficient muscular dystrophy and a mean age of 17.2 yr (range, 5-41) satisfied
      criteria for having dilated cardiomyopathy (DCM) and received digitalis and
      diuretics. Nine of the 14 patients were symptom-free, despite left ventricular
      ejection fractions (LVEFs) of 25-40%. The five patients with symptomatic heart
      failure had severe ventricular dilatation, with LVEFs < 25%. Two of the five
      patients died of heart failure within 1 yr. For the remaining three patients, we
      evaluated the addition of the angiotensin-converting enzyme (ACE) inhibitor
      enalapril and, subsequently, the use of beta-blockers to the therapeutic regimen.
      Addition of these medications, never before attempted in the management of
      cardiomyopathy associated with generalized myopathic disease, complemented each
      other in relieving symptoms and reversing signs of congestive heart failure and
      DCM. We conclude that the combination of ACE inhibitor and beta-blocker deserves
      further exploration for inclusion in any management regimen for the treatment of
      muscular dystrophy-associated cardiomyopathy.

PMID- 7576412
TI  - H-reflex recovery curve and reciprocal inhibition of H-reflex of the upper limbs
      in patients with spasticity secondary to stroke.
AB  - The H-reflex recovery curve of the lower limb is considered a useful test for the
      diagnosis of spasticity, and recently the reciprocal inhibition of the H-reflex
      has proven to be abnormal in patients affected with spasticity. We studied the H
      reflex recovery curve and the reciprocal inhibition of the H-reflex in the upper
      limb of a group of 33 patients with different degrees of spasticity secondary to
      stroke. Results were compared with those of 25 controls. The aim of this study
      was to investigate if the two tests showed any direct correlation with the degree
      of spasticity and, furthermore, with other clinical measures that are present in
      patients with spasticity as part of an upper motoneuron syndrome (i.e., changes
      in muscle tone, reflexes, force, etc.). The results showed an abnormality of both
      tests in most patients (decrease of the three phases of inhibition in the
      reciprocal inhibition test and increase of the late facilitation part of the H
      reflex recovery curve), and these abnormalities seem mostly to be related to
      muscle tone, most important being the degree of correlation between tone and
      changes in abnormality of the H-reflex recovery curve (P < 0.03).

PMID- 7576413
TI  - Isokinetic and isometric strength in osteoarthrosis of the knee. A comparative
      study with healthy women.
AB  - Dynamic stability of the knee joint depends on the appropriate strength ratio of
      quadriceps and hamstring muscles. The purpose of this investigation was to
      determine the maximum peak torque (MPT) and MPT ratios of hamstrings to
      quadriceps (H/Q) muscles in patients with knee osteoarthritis (OA). Two groups of
      patients were included in the study. The first group consisted of 30 patients
      (Group A) with the clinical and radiologic findings of knee OA. The second group
      consisted of 30 patients (Group B) exhibiting knee joint pain without
      roentgenologic findings of knee OA. The findings of two patient groups were
      compared with each other and also with 30 healthy subjects (Group C). Isokinetic
      (at 60 degrees/s and at 180 degrees/s) and isometric (at 30 degrees and at 60
      degrees of knee flexion) tests were performed by the rate-limiting isokinetic
      dynamometer system. Isokinetic and isometric MPT loss of knee flexors and
      extensors was found in both patient groups with respect to controls, but MPT
      ratios of H/Q muscles did not show a statistically significant difference
      compared with the control group. This may be related to the equal strength loss
      of knee flexors and knee extensors in patients with knee OA. It is concluded that
      strengthening exercises of hamstring muscles is as important as quadriceps
      strengthening in rehabilitation of knee OA.

PMID- 7576415
TI  - Neurologic recovery and functional improvement after vecuronium-induced
      quadriparesis.
AB  - Vecuronium bromide (Norcuron, Organon, Inc., West Orange, NJ) is a common
      neuromuscular blocking agent used to facilitate mechanical ventilation. Cases
      have been reported in which prolonged use of vecuronium resulted in severe motor
      neuropathy, with or without myopathy. However, the time course of recovery, the
      functional prognosis, and the use of inpatient rehabilitation is not well
      established. We are reporting the functional recovery of two cases with the
      diagnosis of severe vecuronium motor neuropathy and/or myopathy. The patients
      presented with pneumonia and meningococcemia, respectively, and received
      vecuronium during ventilatory support, which lead to quadriparesis. In one
      patient, vecuronium toxicity occurred while neuromuscular junction monitoring was
      in place. Significant improvement was noted during an average of 3 to 4 wk in a
      comprehensive inpatient rehabilitation program, documented by the improvement in
      total motor Functional Independence Measure scores for patient 1 (from 15 to 71)
      and for patient 2 (from 65 to 84). In addition, the distal compound motor
      amplitudes showed a 4-fold increase for the ulnar, a 7-fold increase for the
      median, an 11-fold increase for the peroneal, and a 3-fold increase for the
      tibial nerves on follow-up nerve conduction studies correlating with neurologic
      recovery. In summary, even when patients present with quadriparesis, the recovery
      after vecuronium toxicity appears to be favorable.

PMID- 7576414
TI  - Disability among the elderly of Taiwan.
AB  - A cross-sectional study on the correlates of elderly disability was conducted in
      Taiwan. A total of 400 subjects was randomly selected according to Barthel Index
      scores from among 2600 subjects, which was a sample of a previous community-based
      health survey of elderly aged 65 or over. After comprehensive interviews and
      examinations of the subjects, disability dimensions and its correlates were
      identified. Results showed elderly with lower Mini-Mental State Examination
      scores and chronic diseases (such as stroke, pressure sores, hypertension,
      fracture, etc.) were more physical-functionally and socially disabled. This
      suggests that prevention and treatment of chronic diseases should be pursued
      further and that further assessment of cognitive-mental status in the elderly is
      warranted. In addition, males were more disabled than females in a physical
      functional aspect, which may be the consequence of the traditional Chinese
      cultural effect.

PMID- 7576416
TI  - Managed care and its effect on residency training in physical medicine and
      rehabilitation. A commentary.

PMID- 7576417
TI  - Strong quasi-experimental designs for research on the effectiveness of
      rehabilitation.
AB  - Medical rehabilitation needs better understanding of the effectiveness of its
      treatments and of patient characteristics most responsive to alternative
      intervention strategies. The goal of this paper is to improve understanding of
      research design in medical rehabilitation. More specifically, it describes two
      potentially rigorous but infrequently used "quasi-experimental" research designs-
      the regression-discontinuity design and the multiple interrupted time-series
      design. These are contrasted with the strongest research design--the randomized
      experiment--and to weaker designs, such as the nonequivalent group designs. Pre
      experimental research, including qualitative, descriptive, and predictive
      studies, should not be confused with experimental research designs. More frequent
      use of randomized experimental and strong quasi-experimental designs can provide
      knowledge that will augment the effectiveness of rehabilitation practice.

PMID- 7576419
TI  - Profiles of neuromuscular diseases. Limb-girdle syndromes.
AB  - Sixty-six individuals with Limb-Girdle Syndrome (LGS) were evaluated over a 10-yr
      period and classified into three types: 19 severe autosomal recessive muscular
      dystrophy of childhood (ARMDC), alternatively referred to by some as SCARMD, 18
      autosomal dominant late onset (ADLO), and 29 pelvifemoral (PF) individuals. ARMDC
      subjects showed the greatest weakness, 2.5 +/- 1.0, mean Manual Muscle Test (MMT)
      grade for all muscles combined, and the only significant progression of loss of
      strength, -0.59 MMT unit decline per decade. Strength loss in ADLO and PF types
      was about the same, 3.7 +/- 0.7 and 4.0 +/- 0.7 grades, respectively.
      Quantitative strength measurements in ADLO and PF types were more sensitive than
      MMTs, showing losses of 30-40% strength in muscle groups with MMT grades of 4 or
      higher. All three types showed greater proximal and lower extremity weakness but
      usually no difference between flexor and extensor strength. There was a high
      percentage (44%) of mild very slowly progressive scoliosis in ARMDC, but spine
      deformity was unusual in ADLO and PF (11%) LGS. Contractures were few, slowly
      progressive, and usually mild in severity in all types, although more frequent in
      ARMDC. There also was a low frequency of severe restrictive lung disease in all
      types (10%) but a high percentage of electrocardiogram abnormalities (62-73%).
      The most common electrocardiogram abnormalities were increased R/S ratio in V1
      and infranodal conduction defects. Intellectual and cognitive functions were
      within normal limits. Mobility and extremity function reflected the strength
      differences between the ARMDC and other types of LGS. Eight-five percent of ARMDC
      individuals relied on a wheelchair for all or part of their mobility, and all
      were unable to complete timed motor performance tests within the 99th percentile
      range for controls.

PMID- 7576418
TI  - Profiles of neuromuscular diseases. Myotonic dystrophy.
AB  - Ninety-two individuals with myotonic dystrophy (MD) were evaluated prospectively
      over a 10-yr period and separated into two types, 75 noncongenital (NC-MD) and 17
      congenital (C-MD) MD. Muscle weakness was relatively mild and similar in both
      types, 4.0 +/- 0.7 manual muscle test (MMT) scores for NC-MD and 3.8 +/- 0.7 in C
      MD. However, weakness was progressive in the former, -0.36 MMT units per decade,
      and nonprogressive in C-MD. Weakness was usually generalized in both types, with
      no significant differences between upper and lower extremities or the proximal
      and distal muscles. Flexor and extensor differences were variable. Quantitative
      strength measurements showed a similar pattern but were more sensitive showing
      marked strength losses of 40-50% in muscle groups with MMT scores of four or
      more. There was a high frequency (47%) of relatively mild, nonprogressive
      scoliosis in C-MD, whereas spine deformity was unusual in NC-MD. Contractures,
      usually at the ankles, were also more common in C-MD. In NC-MD and C-MD,
      respectively, there was a low frequency of severe restrictive lung disease (14
      and 20%) but a high percentage of significant electrocardiographic (ECG)
      abnormalities (75 and 81%), including conduction defects. There was a marked
      difference between the two types of MD in intellectual and cognitive function.
      Seventy-five percent of C-MD subjects showed impairment, frequently severe,
      compared with 35% impairment, usually mild, for NC-MD individuals. Functional
      evaluation was not markedly affected, but timed motor performance showed
      significant disability especially for individuals with C-MD.

PMID- 7576420
TI  - Profiles of neuromuscular diseases. Facioscapulohumeral muscular dystrophy.
AB  - Data were collected prospectively over a 10-yr period from 53 subjects with
      facioscapulohumeral muscular dystrophy (FSHD) to provide a profile of impairment
      and disability. Manual muscle testing (MMT) indicated greater involvement of
      proximal musculature, although a subgroup demonstrated early weakness of the
      ankle dorsiflexors. Asymmetry of upper extremity musculature was noted, with
      greater weakness of selected dominant limb muscle groups. Weakness, in general,
      was relatively mild, with an overall mean MMT score of 3.7 units. The rate of
      strength loss was quite slowly progressive, a decline of only -0.22 MMT units per
      decade of age. An early age of onset was associated with greater likelihood of
      more severe and progressive weakness. Isometric and isokinetic quantitative
      strength testing revealed that all muscle groups were 36-68% weaker than a
      control population. Although nearly 50% of the subjects had vital capacity
      evidence of restrictive lung disease, only 13% had severe involvement, and only
      22% had a history of pulmonary complications. There was no age or disease
      duration effect on pulmonary function measurements or complications. As with the
      other neuromuscular diseases, maximal expiratory pressure measurements were more
      sensitive than other pulmonary function tests. Abnormal electrocardiogram
      findings were rare and minor and not related to overt cardiac disease.
      Contractures were rare and mild. Thirty-five percent of the patients had spine
      deformity; however, most had hyperlordosis. Intellectual function was normal, and
      there were few abnormalities on personality tests. Functional testing
      demonstrated wide variation in disability with FSHD, but motor weakness uniformly
      translated into impaired motor performance skills. This profile demonstrates the
      clinical heterogeneity of FSHD.

PMID- 7576421
TI  - Profiles of neuromuscular diseases. Hereditary motor and sensory neuropathy,
      types I and II.
AB  - Data were collected prospectively for an impairment and disability profile for 86
      hereditary motor and sensory neuropathy, types I and II (HMSN) subjects over a 10
      yr period. Our data confirm that HMSN is a slowly progressive disorder that has a
      very heterogeneous phenotypical expression. The disorder was characterized
      primarily by diffuse muscle weakness with prominent distal atrophy. The mean
      manual muscle test (MMT) strength grade for all muscle groups combined was 3.9 +/
      0.7 MMT units. There was a slowly progressive decline in strength, only -0.15
      MMT units per decade. Distal muscle groups were weaker than proximal muscles, and
      the decline in strength of the ankle muscles was greater than for the proximal
      muscles. There was no side dominance. Anthropometric data revealed that distal
      atrophy may be masked by subcutaneous fat in female subjects. On average, HMSN
      subjects produced 20-40% less force than normal controls, using quantitative
      isometric and isokinetic strength measures, even when MMT scores were normal.
      Pulmonary and cardiac abnormalities were uncommon, as were spine deformity and
      joint contractures. Only 1 individual had severe restrictive lung disease, and 12
      (14%) had a history of significant respiratory complications with no age or
      disease duration effect. As with the other neuromuscular diseases, maximum
      expiratory pressure was more affected than forced vital capacity. Fourteen
      individuals (30%) had abnormal electrocardiograms, and six (7%) had a history of
      significant cardiovascular complications with no age or disease duration effect.
      Kyphosis was the major spine deformity. Cardiopulmonary responses to exercise
      testing were markedly abnormal, showing reduced aerobic capacity. Functional
      evaluations and timed motor performance tests showed only mild disability in most
      individuals. With timed motor performance testing muscle weakness translated to
      impaired motor performance skills. Overall, mean scores on intellectual function
      and neuropsychologic profiles were normal.

PMID- 7576423
TI  - Profiles of neuromuscular diseases. Design of the protocol.
AB  - The purpose of this 10-yr investigation was to develop comprehensive impairment
      and disability profiles of the clinical characteristics of seven neuromuscular
      diseases: spinal muscular atrophy, hereditary motor sensory neuropathy, Duchenne
      muscular dystrophy, Becker's muscular dystrophy, facioscapulohumeral muscular
      dystrophy, limb-girdle syndrome, and myotonic dystrophy. Based on the World
      Health Organization's classification of disablement, as applied to neuromuscular
      diseases, impairment was evaluated by measurements of strength, range of motion,
      spine deformity, cardiac and pulmonary function, and intellectual capacity.
      Disability was evaluated by measures of mobility and upper extremity function,
      cardiopulmonary adaptations, cardiac and pulmonary complications, and
      psychosocial adjustment.

PMID- 7576424
TI  - Profiles of neuromuscular diseases. Duchenne muscular dystrophy.
AB  - One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were
      followed over a 10-yr period to provide a profile of impairment and disability.
      The median height and weight of DMD boys were normally distributed before ages 9
      10, but during the second decade height was markedly reduced, and weight was no
      longer normally distributed. Younger boys gained more weight than normals,
      whereas older individuals actually showed weight loss. Manual muscle test (MMT)
      measurements showed loss of strength in a fairly linear fashion from ages 5-13
      yr, -0.25 MMT units per year. Upper extremity muscles were stronger than lower
      extremity muscles, proximal muscle groups were weaker than distal muscle groups,
      and extensor muscles were weaker than flexor muscles. There was no side
      dominance. There was a change in the rate of strength loss at 14-15 yr, and the
      decline slowed to only -0.06 MMT units per year. Although MMT and quantitative
      strength measurement profiles were similar, the latter were far more sensitive.
      In general, by the time strength declined to MMT grade 4, isometrically measured
      strength was 40-50% of normal control values. Joint contractures were rare before
      age 9, increased in frequency and severity with age, and were present in most
      individuals older than 13. Lower extremity contractures were strongly related to
      onset of wheelchair reliance, but there was no association between muscle
      imbalance around a joint. The prevalence of scoliosis increased between ages 11
      and 16, with about 50% of the boys acquiring scoliosis between ages 12 and 15,
      corresponding to the onset of the adolescent growth spurt. Wheelchair reliance
      and scoliosis were both age-related. Percent predicted forced vital capacity
      declined at different yearly rates: ages 7-10, -0.3%; ages 10-20, -8.5%; after
      age 20, -6.2%. There was a direct relationship between percent predicted FVC and
      MMT scores. Decreased airway pressures, especially maximal expiratory pressure,
      appeared earlier than reductions in FVC but followed the same pattern. Thirty
      percent of the DMD boys had a history of respiratory complications, and the
      frequency increased with age. Spine deformity did not have a significant additive
      effect on the age-related decrement in pulmonary function. There was a high
      occurrence (79%) of abnormal electrocardiograms with age-related progression of
      some abnormalities, but only 30% of the patients had a history of cardiovascular
      complications. Functional level grades and timed motor performance measurements
      had a nonlinear relationship with strength and age.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7576422
TI  - Profiles of neuromuscular diseases. Spinal muscular atrophy.
AB  - Forty-five individuals with spinal muscular atrophy (SMA) types II and III were
      evaluated prospectively over a 10-yr period to develop an impairment and
      disability profile. SMA II subjects showed marked weakness and progressive
      decline of strength. Mean manual muscle test (MMT) score for all muscles combined
      was 2.3 +/- 0.6, with a decline in strength of -0.24 MMT units per decade. SMA
      III individuals had a relatively static or very slowly progressive course and
      were far stronger. Mean MMT score for all muscles combined was 3.8 +/- 0.7, and
      the decline in strength per decade was not significant. In both types proximal
      weakness was greater than distal, but there was greater involvement of the lower
      extremities and the extensor muscle groups only in SMA II. Contractures,
      progressive scoliosis, and restrictive lung disease (RLD) were present in most of
      the SMA II individuals, but these complications were rare in SMA III. Maximal
      expiratory pressures were affected earlier and to a greater degree than vital
      capacity. Seventy-eight percent of those with SMA II had scoliosis with a mean
      Cobb angle of the primary curve of 62 +/- 37 degrees. Forty-one percent had
      severe RLD, and 17% had moderate RLD. In both types, 63% had abnormal
      electrocardiograms although most had minor findings. Timed motor performance and
      functional evaluations indicated that muscle weakness translated to substantial
      disability in both SMA II and III, with more severe impairment noted in SMA II.
      Neither type was associated with abnormal means scores on intellectual and
      neuropsychologic test batteries.

PMID- 7576426
TI  - 13th Annual meeting of the International Society of Blood Purification. Kyongju,
      Korea, September 27-29, 1995. Abstracts.

PMID- 7576425
TI  - Profiles of neuromuscular diseases. Becker's muscular dystrophy.
AB  - Fifteen subjects with Becker's muscular dystrophy (BMD) were studied
      prospectively over a 10-yr period to provide a profile of impairment and
      disability. Proximal lower extremity musculature (particularly the hip and knee
      extensors), ankle dorsiflexors, and neck flexors showed significantly early
      weakness. Extensor muscle groups were weaker than flexor muscles at the elbow and
      knee. The mean manual muscle test (MMT) strength grade for all muscle groups
      combined was 3.7 +/- 0.8 MMT units. There was a slowly progressive decline in
      strength, only -0.31 MMT units per decade, and the decline was relatively equal
      in all muscle groups. There was not side dominance. Severe contractures did not
      appear to be a problem until after transition to a wheelchair, and scoliosis was
      rare. Restrictive lung disease occurred as a late complication in a small
      percentage of cases; however, maximal expiratory pressure was significantly
      reduced early in the disease. Only two individuals (19%) had severe restrictive
      lung disease and a history of significant respiratory complications. There was a
      slight but significant decline in forced vital capacity and maximal expiratory
      pressure with age and disease duration. The cardiomyopathy in BMD appeared to be
      disproportionately severe in some cases. Eleven individuals (73%) had abnormal
      electrocardiograms, and five (25%) had a history of significant cardiovascular
      complication, with no age or disease duration effect. Functional evaluations and
      timed motor performance tests showed only mild disability in most individuals.
      Mean intellectual and neuropsychologic function was within normal limits, but
      with a large variability in intelligence quotient scores. This report and others
      suggest a tremendous heterogeneity of severity among males with BMD.

PMID- 7576427
TI  - [Old wine in new bottles: the "promille-killer" Party Plus].
AB  - We report about the allegedly new sobering up preparation called PARTY-PLUS, the
      ingredients of which resemble very much those of the inefficient "drink with a
      sobering up effect NEUKAMM-lemonade". In a drinking experiment Verum vs. Placebo
      (a light mineral water) the inefficiency of the alcohol elimination kinetics is
      proved once again, especially with regards to the extent of success suggested in
      advertising. Official bodies of administration of justice and legislation are
      called upon to oppose such doings of manufacturers and distributors more firmly.
      This is necessary because expected side effects and health hazards due to the
      high fructose contents are deliberately played down or concealed altogether.

PMID- 7576428
TI  - [Revoking the right to drive--a blunt weapon against alcohol intoxicated drivers,
      hit-and-run drivers and speed limit and red light offenders?].
AB  - The differences of the driving ban are determined by the text of law and the type
      of offence (drink driving, hit-and-run driving) or minor infringement. "Levelling
      down" is inappropriate. Character defects can be compensated by re-training
      programmes for drivers, years of sound driving experience and economic
      difficulties (unemployment). In these cases--especially if it is a first offence-
      the best way out of the dilemma is an exemption from the driving ban. Despite
      years of good reputation the exemption from the driving ban is out of the
      question if alcohol abuse is reinforced by violence.

PMID- 7576429
TI  - [Experiences after 2 years observation of a chronic alcoholic].
AB  - Doctors of legal medicine often have to act as experts when it comes to
      determining the influence of alcohol or drugs. For this work it would be
      desirable to have many years of experience in dealing with alcoholics or
      occasional drinkers. Therefore, drinking experiments have always been part of the
      training of a doctor of legal medicine, as well as playing an important role in
      legal practice. It would be wrong if the experience in the legal sense were to be
      considered sufficient for standardising the judgement of legal responsibility.
      However, this is often attempted. Too much schematism should be avoided with the
      so called per mille graduation.

PMID- 7576430
TI  - [Dental prosthesis--residual alcohol content?].
AB  - The possible influence of complete or partial dental prosthesis when detecting
      breath alcohol by means of the breath alcohol analyser "Alcomat" was investigated
      in a study. During the study, volunteers were asked to rinse their mouths with
      different types of alcohol such as beer, wine, schnapps and sweets containing
      alcohol. No influence of the dental prosthesis on the results could be detected.
      A dental prosthesis neither prolongs the duration of residual alcohol detection,
      nor does it affect the period of false positive breath alcohol detection. In
      individual cases the waiting period of 15 minutes between the last alcohol
      consumption and the breath alcohol test--as legally enforced in Austria--has
      proved to be too short.

PMID- 7576431
TI  - [Initial experiences with the "0.8 promille regulation in Thuringen].
AB  - Blood samples sent in for analysis in 1992 and 1993 showed an increase in the BAC
      values of offenders in the "driving under the influence" category. At the same
      time it was found that, proportionally, the number of people whose BAC was below
      0.8% had dropped. The same trend could be observed in the "road accident"
      category. This trend continued throughout 1994. One can therefore assume that the
      introduction of the "0.8% law" in eastern Germany has brought with it an increase
      in the level of intoxication of people driving under the influence of alcohol.

PMID- 7576432
TI  - Biosensing with surface plasmon resonance--how it all started.
AB  - A subjective description is given of how the development of surface plasmon
      resonance for immunosensing began. The main differences between the initial
      experiments and a commercially available instrumentation are pointed out. For the
      practical use of surface oriented methods for biosensing it is noted that the
      arrangements around the optical system itself, such as the sensing chip or sample
      cell, are most important. It is concluded that the instrumentation developed can
      be used not only for immunosensing but also for "real time biospecific
      interaction analysis" in general. It is pointed out that the use of surface
      plasmon resonance for detection is only one possibility and that many new
      (optical) methods for real time biospecific interaction analysis have been and
      will be developed.

PMID- 7576433
TI  - Enzyme biosensor for urea based on a novel pH bulk optode membrane.
AB  - A new, absorbance-based enzymatic biosensor membrane for determination of urea is
      described. A lipophilic, fully LED- and diode laser-compatible pH sensitive dye
      was incorporated into a plasticized, carboxylated poly(vinyl chloride) membrane
      and served as the optical transducer of the sensor. Urease was covalently linked
      to the surface of the pH bulk optode membrane to form a very thin cover. The
      resulting biosensor membrane allows rapid determination of urea over the 0.3 to
      100 mM range. The reproducibility, stability, and effects of pH and buffer
      concentration on the response of sensor are reported. The preparation of the pH
      transducer and the immobilization of the enzyme are simple and may easily be
      adopted to other biosensor types.

PMID- 7576434
TI  - Tetracyanoquinodimethane mediated glucose sensor based on a self-assembling
      alkanethiol/phospholipid bilayer.
AB  - An amperometric tetracyanoquinodimethane (TCNQ) mediated biosensor for glucose is
      described, based on a self-assembling alkanethiol/phospholipid bilayer laid down
      onto a gold surface. Gold was sputter deposited onto chromium coated silicon
      wafers to a thickness of 200 nm. A monolayer of alkanethiol was allowed to self
      assemble from an ethanolic solution of dodecanethiol onto a freshly cleaned gold
      electrode in an overnight incubation. The monolayer was characterized by
      ellipsometric, impedance and cyclic voltammetry measurements (capacitance = 1.60
      +/- 0.06 microF/cm2, and thickness 1.34 +/- 0.15 nm). A mixture of phospholipid
      liposomes containing free amino groups was placed on the monolayer and allowed to
      incubate overnight. The self-assembly of a phospholipid monolayer and allowed to
      incubate overnight. The onto the alkanethiol monolayer, resulted in the formation
      of a bilayer. The formation of bilayer was again characterized by impedance and
      cyclic voltammetry measurements (capacitance = 0.98 +/- 0.09 microF/cm2, and
      thickness = 1.85 +/- 0.22 nm). TCNQ has been incorporated into the liposomes
      before the formation of the bilayer. Glucose oxidase was cross-linked with the
      amino-groups of the phospholipids using bis [2-(sulphosuccinimiidooxicarbonyloxy)
      ethyl] sulphone. TCNQ which was incorporated in the bilayer acted as an efficient
      mediator to regenerate glucose oxidase. Cyclic voltammetry of the modified
      electrode and a response curve for the glucose sensor are reported.

PMID- 7576435
TI  - Impedance based sensing of the specific binding reaction between Staphylococcus
      enterotoxin B and its antibody on an ultra-thin platinum film.
AB  - Immunobiosensing techniques to measure specific antigen-antibody binding
      reactions are important in the development of biosensor applications in
      biotechnology, in vitro diagnosis, medicine and food technology. An
      immunobiosensor was constructed to measure the specific binding reaction between
      Staphylococcus enterotoxin B (SEB) and anti-SEB antibodies. The biosensor
      comprised an anti-SEB bioactive layer covalently immobilized on an ultra-thin
      platinum (Pt) film sputtered onto a 100 nm thick silicon dioxide layer on a
      silicon chip. The Pt film was discontinuous with a normal thickness of 25 A. The
      impedance of the Pt film decreased during the binding of the anti-SEB to SEB in
      phosphate buffered saline (PBS) at room temperature. The impedance decreases were
      irreversible in PBS before saturation of the specific binding sites. When
      saturated, the impedance at 100 Hz was 14% of the value obtained for the fresh
      anti-SEB layer in PBS. The magnitude of the impedance (Z) decrease followed a
      simple relationship with SEB concentration in the range between 0.389 and 10.70
      ng/ml SEB. The specificity of the biosensor was demonstrated by showing that no
      irreversible impedance decreases occurred when the sensor was exposed to 100
      ng/ml kappa-casein, or alpha-lactalbumin, in PBS.

PMID- 7576436
TI  - Amperometric detection of alkaline phosphatase activity at a horseradish
      peroxidase enzyme electrode based on activated carbon: potential application to
      electrochemical immunoassay.
AB  - Amperometric detection of alkaline phosphatase activity has been achieved using 5
      bromo-4-chloro-3-indolyl phosphate (BCIP) as the enzyme substrate. The production
      of hydrogen peroxide from the dephosphorylation of BCIP was measured using an
      activated carbon electrode with horseradish peroxidase immobilised to its surface
      by simple passive adsorption. This method was easily capable of measuring 10(-12)
      M alkaline phosphatase and had a calculated detection limit of 2.2 x 10(-14) M.
      The horseradish peroxidase electrode system was investigated further as a method
      for non-competitive electrochemical enzyme immunoassay using thyrotropin (TSH) as
      the model analyte. This was realised by co-immobilization to the electrode
      surface of both horseradish peroxidase and an anti-thyrotropin monoclonal
      antibody. After addition of the analyte, a second biotinylated anti-thyrotropin
      monoclonal antibody and the substrate, streptavidin-labelled alkaline phosphatase
      was added and the current (generated by enzyme channelling of hydrogen peroxide)
      measured as a function of TSH concentration. Thus, the activated carbon electrode
      was used as a combined immunological capture phase and amperometric detection
      system.

PMID- 7576437
TI  - Amperometric thin film biosensors based on glucose dehydrogenase and Toluidine
      Blue O as catalyst for NADH electrooxidation.
AB  - Amperometric glucose sensors were constructed based on solid graphite electrodes,
      surface-modified with NAD+ dependent glucose dehydrogenase (GDH), Toluidine Blue
      O (TBO), and protective ionic polymers. The electrocatalytic oxidation of NADH
      was evaluated from cyclic voltammetry with TBO dissolved, adsorbed, and
      electrostatically or covalently bound to polymers. The NADH and glucose sensors
      constructed were investigated and operated at 0 mV vs. Ag/AgCl using single
      potential step chronoamperometry. The operational stability of the glucose
      sensors was limited by leakage of NAD+. A glucose sensitivity much higher than
      carbon paste electrode was found. A sensitivity as high as 25 microA cm-2 mM-1
      was achieved.

PMID- 7576438
TI  - Poly(binaphthyl-20-crown-6) as receptor based molecular selective potentiometric
      electrodes for catecholamines and other 1,2-dihydroxybenzene derivatives.
AB  - A novel type of poly(crown ether) electrode that is capable of selectively
      determining some 1,2-dihydroxybenzenes has been developed. A lipophilic
      macrocyclic crown ether, binaphthyl-20-crown-6, is electrochemically deposited on
      a platinum disc electrode. The film obtained is used as a sensory element for a
      potentiometric electrode for the determination of some neurotransmitters, namely,
      catecholamines. The new electrode is also capable of discriminating the steric
      shapes of 1,2-dihydroxybenzene moieties. The response of the new electrode is
      based on the principle of 'host-guest' chemistry. The potentiometric response is
      dependent on the pH of the solution and the nature of the buffer medium. The new
      sensor electrode has a useful analytical range of 1.5 x 10(-8) M-2 x 10(-5) M
      with a linear dynamic range between about 1 x 10(-7) M-5 x 10(-4) M with a 'super
      Nernstian' slope of 110-130 mV/decade. The detection limit in phosphate buffer
      (0.1 M, pH 9.4) is ca. 3 x 10(-8) M for catecholamine. The sensor electrode is
      virtually insensitive towards interference from most inorganic ions and
      circumvents the interference from ascorbic acid, which is often found using
      amperometric methods in biological samples. A partial response mechanism of the
      present electrode is discussed, supported by results of electron dispersive
      analysis by x-rays (EDAX).

PMID- 7576439
TI  - Biosensor based on an enzyme modified electrode for highly-sensitive measurement
      of polyphenols.
AB  - The use of glucose dehydrogenase from Acinetobacter calcoaceticus for highly
      sensitive measurement of polyphenols, based on bioelectrocatalytic analyte
      recycling, has been demonstrated. A polyphenol (analyte) is oxidized on the
      surface of a glassy carbon electrode at an anodic potential and is regenerated by
      immobilized glucose dehydrogenase (GDH) in the presence of glucose, resulting in
      an amplified response. The dynamic properties of the enzyme-modified glassy
      carbon electrode allow the convenient monitoring of subnanomolar analyte
      concentration. The detection limits for p-aminophenol and norepinephrine are 0.2
      nM and 0.5 nM, respectively.

PMID- 7576441
TI  - The design of enzyme sensors based on the enzyme structure.
AB  - The size of some of the reported electron mediators for glucose oxidase compared
      with the available space to penetrate the active site, implies that electrons
      have to move along the protein structure. Theoretical and experimental evidence
      predicts that it is possible to have electron transfer at the required rate used
      in biosensors (200 to 1840 electrons s-1) for the distances in glucose oxidase
      (20 to 25 A). Use of the program "Pathways" (together with the knowledge of the
      enzyme structure) allowed us to find an electron pathway within the enzyme. This
      pathway has a maximum electron coupling between the active site and the surface
      of the enzyme. The pathway reaches the surface near functional groups that can be
      used for oriented immobilization of the enzyme. Experimental confirmation of this
      particular pathway has been attempted but it is still elusive.

PMID- 7576440
TI  - A silicon-based biosensor for real-time toxicity testing in normal versus cancer
      liver cells.
AB  - The potentiometric alternating biosensor (PAB) system has been utilized to
      monitor the effects on normal versus cancer cells of Mitoxantrone, a potent
      inhibitor of nucleic acid synthesis commonly utilized in the clinical treatment
      of hepatocarcinomas. In this first series of toxicity tests, we have utilized a
      primary culture of rat hepatocytes and a stabilized line named HepG2 from a human
      hepatoma. Primary cultures of hepatocytes represent a unique tool in
      toxicology/pharmacology as shown in previous works. A suitable microvolume flow
      chamber has been designed and produced. The chamber is equipped with inlet and
      outlet circuits and with a fixed transducer (Si/SiO2/Si3N4 chip) facing a cover
      slip on which cells grow. The PAB system is here utilized only in the pH
      sensitive configuration with a single measuring spot, warranting an accurate
      determination of the change in the extracellular acidifcation rate resulting from
      drug administration. We have also observed the changes in the acidification rate
      of 3T6 mouse fibroblasts, induced by a treatment with Ara-C, a well-known DNA
      antimetabolite. New insights can be obtained from these studies into the drug
      response of normal versus cancer cells and into the feasibility of real-time PAB
      monitoring of drug toxicity and efficacy, towards effective human cancer
      treatment. The effect of increasing drug concentrations on cellular metabolism is
      here compared with the results obtained from conventional tests (optical
      microscopy, Neutral Red and Trypan Blue assays).

PMID- 7576442
TI  - [Gas sterilization with gas hydrogen peroxide: a new technology in the
      pharmaceutical industry].
AB  - This article shows the bactericidal capacity of hydrogen peroxide vapor,
      particularly if used through VHP vaporizer (Vaporizer Hydrogen Peroxide) which
      was recently developed and used in the pharmaceutical sector. After a short
      description technologies and of the characteristics of the chemical agents used
      in these technics, will illustrate the machine (VHP), its functioning and its
      possible application fields. The review ends with the illustration of a number of
      experiments, tests and validation trials which stand out from technical point of
      view.

PMID- 7576443
TI  - Effect of manufacturing technology on the dissolution of ampicillin tablets.
AB  - The effect of the manufacturing technology on the dissolution of ampicillin
      tablets have been analyzed. Several kinetic parameters were then calculated. The
      dissolution rate of ampicillin increases in tablets prepared by direct
      compression or dry granulation, with microcrystalline cellulose and colloidal
      silicon dioxide. Studies of in vitro bioequivalence of the pharmaceutical
      products available in the Argentine market were performed. We concluded that not
      all commercial products are equivalent.

PMID- 7576444
TI  - Synthesis of esters of aliphatic and aromatic carbamic acids. A comparative study
      of properties and local anesthetic activity of these compounds.
AB  - Four basic esters of cyclohexancarbamic acid and their salts with hydrochloride
      were synthesized and evaluated for local anesthetic activity. It was found that
      also aliphatic carbamates studied exhibit local anesthetic activity comparable
      with the activity of analogous esters of aromatic (2-methoxyphenyl) carbamic
      acid. Our comparative investigation shows that the presence of aromatic group in
      the ester of carbamic acid influences local anesthetic activity, however the
      occurrence of aromatic moiety is not necessary condition for their activity.

PMID- 7576445
TI  - Bioavailability of buserelin and gonadorelin in suspensions.
AB  - There have been determined parameters defining biological availability of
      gonadorelin and buserelin marked 125 J. Hormonal preparations were hypodermically
      administered to the rats in suspensions containing zinc ions of the molar ratio
      of the hormone: zinc 1:5. It has been stated that buserelin in suspension is
      better available to an organism than gonadorelin .

PMID- 7576447
TI  - Stability study of azlocillin sodium in glass bottles and PVC bags containing
      intravenous admixtures.
AB  - The kinetics of degradation of azlocillin sodium in four intravenous admixtures
      was investigated at different temperatures. The effect of temperature has been
      determined and from this data, by applying of Arrhenius-law, the stability of
      azlocillin sodium at 25 degrees C has been predicted and the t90 was determined.
      Admixtures containing azlocillin sodium (0.01 g ml-1) were prepared in 0.9%
      sodium chloride injection, in 5% dextrose solution, in 5% levulose solution and
      in Ringer's lactate solution. The admixtures were stored at 30 degrees, 40
      degrees and 50 degrees C in either polyvinyl chloride bags and glass bottles. The
      change in the initial azlocillin sodium concentration was related to the type of
      intravenous solution. No dependence with material of container was found. After
      24 hours, the change in the initial concentration of penicillin was less than 10%
      of the initial concentration in 0.9% sodium chloride and 5% levulose solution.
      However in Ringer's lactate and 5% glucose solution the t90 was lower. These
      results were found in agreement with experimental ones obtained at room
      temperature.

PMID- 7576446
TI  - Cytotoxic activity of diorganotin(IV) complexes of some xanthate derivatives.
AB  - The cytotoxic activities of diorganotin(IV) complexes of some xanthate
      derivatives; R2Sn(SSCOR'), where R = Me, Bu(n), Ph and R' = C6H11 - (CyX),
      CH3NHCHCH2 - (MAEX), (CH3)2NCH2CH2 - (DMAEX), (CH3)2NCH2CH(CH3) - (DMAIX) and
      (C2H5)2NCH2CH2 - (DEAEX), have been studied against Hep-2, Hela, RD, L20B and BGM
      cell lines using the MTT-colorimetric assay. The present results indicated that
      moderate activities were demonstrated by the xanthate complexes of Bu(n)2Sn(IV)
      against four cell lines, whereas no cytotoxic activities were exhibited by both
      Me2Sn(IV) and Ph2Sn(IV) complexes of the xanthates. These activities were
      compared with the cytotoxic activities of two reference standards; the cisplatin
      and paraplatin complexes. The significance of these results is discussed.

PMID- 7576448
TI  - Expanding the scope of applications for C-terminal sequencing.

PMID- 7576449
TI  - Endo-N-acetyl-beta-D-glucosaminidase and peptide-N4-(N-acetyl-glucosaminyl)
      asparagine amidase activities during germination of Raphanus sativus.
AB  - Endo-N-acetyl-beta-D-glucosaminidase (ENGase, EC 3.2.1.96) and peptide-N4-(N
      acetyl-beta-D-glucosaminyl) asparagine amidase (PNGase, EC 3.5.1.52) activities
      were monitored during germination and postgerminative development in Raphanus
      sativus. The PNGase activity was found in dry seeds and its level was constant
      during germination and postgermination. The ENGase activity was first detected
      about 18 hr after the start of imbibition (HAI) and displayed a maximum level at
      36 HAI. After 36 HAI the production of both enzymes was constant until days 4-5.
      Both enzymes displayed substrate specificities corresponding to the potential
      glycoprotein substrates found in plants. They are in agreement (i) with the
      hypothesis that ENGase and PNGase are at the origin of the production of
      'unconjugated N-glycans' and (ii) with the possibility that protein activity
      could be regulated by the removal of N-glycans.

PMID- 7576450
TI  - Purification and partial characterization of a Schizolobium parahyba chymotrypsin
      inhibitor.
AB  - Schizolobium parahyba seed chymotrypsin inhibitor (SPC) is a protein with M(r) of
      20,000 and four half-cystine residues and no free thiol group. SPC is stable at
      temperatures up to 75 degrees at pH 7 but gradually loses activity when kept at
      95 degrees for 1 hr and total inactivation occurs after 5 hr. Amino acid analysis
      shows a high content of glycine, aspartate, glutamate and alanine residues. A pI
      of 4.52 predicted from the amino acid content agrees with experimental results. A
      stable binary complex with M(r) of 45,000, Ki = 5.85 x 10(-8) M and molar ratio
      of 1:1 is formed between SPC and chymotrypsin. The determined single N-terminal
      sequence of SPC shows homology with Kunitz type soybean trypsin inhibitors.

PMID- 7576452
TI  - Dammarane glycosides from aerial part of Neoalsomitra integrifoliola.

PMID- 7576451
TI  - Specific competitive inhibitor of secreted phospholipase A2 from berries of
      Schinus terebinthifolius.
AB  - Two structurally related triterpenoids 1 and 2 from pink peppercorn (berries of
      Schinus terebinthifolius) are identified and characterized as active site
      directed specific competitive inhibitors of the three classes of secreted 14 kDa
      phospholipase A2. The inhibitors not only protect the active site histidine from
      alkylation but also inhibit the action of secreted phospholipase A2 from pig
      pancreas, human synovial fluid, and bee venom. Detailed X-ray crystallographic
      results on the structures of the inhibitors are provided. By physical methods and
      X-ray crystallography the triterpenoids were identified as masticadienoic acid
      and masticadienolic acid (schinol). Several other triterpenoids were ineffective
      as inhibitors of phospholipase A2; however certain ganoderic acid derivatives
      showed noticeable inhibition. Results show that the side chain of these acidic
      tetracyclic terpenoids can access the catalytic-site region of phospholipase A2,
      whereas the acyclic nucleus is at the interfacial recognition region. The
      selectivity of the assay protocol used here is demonstrated by the fact that the
      original screen of ethyl acetate extracts of 60 commercially available spices and
      herbs was carried out with phospholipase A2 from pig pancreas, and only one
      extract showed inhibitory action on the hydrolytic activity in the scooting mode.
      Under such assay conditions the enzyme remains tightly bound to the surface of
      the substrate vesicles. In this way, nonspecific effects of additives that
      promote desorption of the enzyme from the substrate vesicle surface, under
      conditions in which the binding of the enzyme to the vesicle is weak, are
      avoided. The assay protocol is useful for the kinetic characterization of the
      inhibitors of phospholipase A2, and it does not give false positive results with
      amphiphilic and hydrophobic compounds, as is the case with virtually all assay
      systems in use.

PMID- 7576453
TI  - Triterpenoid saponins from Phytolacca rivinoides and Phytolacca bogotensis.
AB  - Investigation of the ethanolic extracts from Phytolacca rivinoides and P.
      bogotensis has resulted in the isolation of five new triterpenoid glycosides of
      serjanic acid. Their structures have been established mainly by spectroscopic
      methods (FAB-MS, 1H, 13C NMR, COSY, NOESY, TOCSY, HETCOR and J-resolved 1H NMR)
      as 3-O-(O-beta-D-galactopyranosyl-(1-->3)-O-beta-D-glucopyranosyl)serjan ic acid
      28-O-beta-D-glucopyranosyl ester, 3-O-(O-beta-D-glucopyranosyl-(1-->3)-O-[beta-D
      galactopyranosyl-(1-->4)] -O- beta-D-glucopyranosyl)serjanic acid 28-O-beta-D
      glucopyranosyl ester, 3-O-(O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D
      glucopyranosyl-(1-->2)- O-beta-glucopyranosyl)serjanic acid 28-O-beta-D
      glucopyranosyl ester, 3-O-(O-beta-D-glucopyranosyl-(1-->3)-O-beta-D
      galactopyranosyl-(1-->4)- O-beta-D-glucopyranosyl)serjanic acid 28-O-beta-D
      glucopyranosyl ester and 3-O-(O-beta-D-galactopyranosyl-(1-->4)-O-[beta-D
      glucopyranosyl-(1-->3)] - O-beta-D-glucopyranosyl)serjanic acid.

PMID- 7576454
TI  - Saracin: a lectin from Saraca indica seed integument recognizes complex
      carbohydrates.
AB  - A lectin isolated from Saraca indica seed integument was purified by affinity
      chromatography on porcine thyroglobulin Sepharose followed by Sephadex G-50 and
      shown to be homogeneous by PAGE. It showed a single band on SDS-PAGE in the
      absence and presence of 2-mercaptoethanol corresponding to a M(r) of congruent to
      12,000, thus indicating it to be a monomer. The lectin agglutinated erythrocytes
      of human A, B, O and AB blood group, animal erythrocytes as well as Ehrlich
      ascites cells. It is a thermostable glycoprotein containing 11.6% carbohydrates
      and large proportions of acidic amino acids. In haemagglutination-inhibition
      assays, among the tested glycoproteins, porcine thyroglobulin having the NeuAc
      alpha (2-6)/(2-3)D-Gal beta (1-4)D-GlcNAc sequence was found to be the most
      potent; however, its asialo counterpart was non-inhibitory. The lectin is present
      solely in the seed integument even in the immature stage. During maturation of
      the seed the lectin activity declined and was completely absent when totally
      matured and dried. Studies in vitro showed that on incubation at 37 degrees the
      seed gradually lost its lectin activity which was completely absent after 62 days
      with 88.5% loss of water. Similar studies on scraped seed integument revealed
      that the lectin activity was lost in 22 days with 87.5% dehydration.

PMID- 7576455
TI  - Purification of a N-acetyl-D-galactosamine specific lectin from the orchid Laelia
      autumnalis.
AB  - From the pseudobulbs of the orchid L. autumnalis a lectin was purified on
      immobilized porcine mucin with A + H blood group substance. This lectin is a
      dimeric glycoprotein of M(r) 12,000 with an Sw,20 of 2.2, showing
      haemagglutinating activity directed mainly to human A1 desialylated erythrocytes.
      The lectin possesses sugar specificity for N-acetyl-D-galactosamine and also
      shows high specificity for glycoproteins containing the T (galactose beta
      1,3GA1NAc alpha 1,0 Ser/Thr) or the Tn antigen (GalNAc alpha 1,0 Ser/Thr).

PMID- 7576456
TI  - Acaricidal and insecticidal activities of cadina-4,10 (15)-dien-3-one.
AB  - The novel assignment of 13C and 1H NMR data for cadina-4,10(15)-dien-3-one
      obtained from Hyptis verticillata is presented. The study revealed that cadina
      4,10(15)-dien-3-one possesses chemosterilant activities against the economically
      important cattle tick, Boophilus microplus, and toxic action against adult Cylas
      formicarius the most destructive pest of sweet potato (I pomoea sp.).

PMID- 7576457
TI  - Dynamics of the biosynthesis of methylursubin in plant cells employing in vivo
      13CNMR without labelling.
AB  - In vivo NMR experiments with a digital 600 MHz instrument, exploiting the natural
      abundance of 13C, allowed us for the first time to follow the biosynthesis of the
      newly detected glycoside, methylursubin (4-methoxyphenyl-O-beta-D-primeveroside),
      from 4-methoxyphenol through the intermediate methylarbutin in cell suspensions
      of the Indian medical plant, Rauwolfia serpentina. The metabolic dynamics
      indicate that, within 48 hr, 4-methoxyphenol is almost completely converted into
      the primeveroside, methylursubin. Because of the higher sensitivity at 150.9 MHz
      compared to that at 100.6 MHz, measuring times could be reduced to 1.5 hr. This
      allows detailed monitoring of the conversion of 4-methoxyphenol with an excellent
      signal-to-noise ratio.

PMID- 7576459
TI  - Steroidal alkaloids of Fritillaria maximowiczii.
AB  - From the bulbs of Fritillaria maximowiczii, in addition to the known jerveratrin
      alkaloid, kuroyurinidine, three new steroidal alkaloids, 23-isokuroyurinidine,
      15,16-seco-22 alpha H, 25 beta H-solanida-5,14-dien-3 beta-ol O-beta-D
      glucopyranosyl-(1-->4)-beta-D-xylopyranoside and hapepunine 3-O-beta-cellobioside
      have been isolated and structurally elucidated.

PMID- 7576458
TI  - Hederagenin glycosides from Pometia eximia.
AB  - Seven new saponins, all glycosides of hederagenin (3 beta,23- dihydroxyolean-12
      en-28-oic acid), were isolated from the stem of Pometia eximia along with
      hederagenin and two known saponins. Their structures were established as 28-O
      beta-D-apiosyl(1-->2)-beta-D-glucopyranosyl-, 3-O-alpha-L- arabinofuranosyl(1-
      >3)[alpha-L-rhamnopyranosyl (1-->2)]-beta-D- xylopyranosyl-, 3-O-beta-D-apiosyl(1
      ->3)[alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-, 3-O-alpha-L
      arabinofuranosyl(1-->3)[alpha-L-rhamnopyranosyl- (1-->2)]-beta-L-arabinopyranosyl
      , 3-O-beta-D-xylopyranosyl(1-->3)[alpha-L- rhamnopyranosyl(1-->2)]-alpha-L
      arabinopyranosyl-, 3-O-beta-D-xylopyranosyl-(1-->3)[alpha-L-rhamnopyranosyl(1-
      >2)]-beta-D- glucopyranosyl-, 3-O-beta-D-galactopyranosyl(1-->3)[alpha-L
      rhamnopyranosyl(1-->2)]-beta- D- glucopyranosyl-hederagenins.

PMID- 7576460
TI  - An impedimetric method for rapid screening of cosmetic preservatives.
AB  - An efficient impedance method was developed for rapid evaluation of cosmetic
      preservatives. The method used decimal reduction time or D-value to assess
      preservative efficacies. The D-value, which was calculated from the plot of Log
      CFU ml-1 versus time by linear regression analysis, could be obtained within 48
      h. Thus, the time required for the challenge test was reduced from 4-8 weeks with
      the standard procedures (eg US Pharmacopeia), to 2 days with the current method.
      A calibration curve (r = -0.95) was established by plotting the Log CFU ml-1
      versus capacitance detection time (DT) of 108 samples. With the calibration, CFU
      can be estimated directly from the impedance test without plating. Two commercial
      biocides and several other chemicals were evaluated in a shampoo by the impedance
      procedure against Pseudomonas aeruginosa. The D-values obtained from the
      impedance test were not significantly different from those produced by the
      conventional plate count method. The technique was found to be particularly
      useful when screening a large number of compounds to find novel preservatives and
      synergistic preservative combinations.

PMID- 7576461
TI  - Microbial transformation of N-heptyl physostigmine, a semisynthetic alkaloid
      inhibitor of cholinesterase.
AB  - The microbiological transformation of N-heptyl physostigmine (L-693,487) (1), a
      semisynthetic physostigmine cholinesterase inhibitor, was investigated using
      Verticillium lecanii MF 5713 (ATCC 74148), Acremonium sp MF 5723 (ATCC 74164) and
      Actinoplanes sp MA 6559 (ATCC 53771). Nine microbial metabolites (2-10) of 1 were
      isolated and purified using reversed-phase HPLC. The structures of the
      metabolites were established using spectroscopic techniques including MS and NMR.
      Some of the microbial metabolites were identical to metabolites present in urine
      of a dog treated with 1.

PMID- 7576463
TI  - Effect of pH, aeration and sucrose feeding on the invertase activity of intact S.
      cerevisiae cells grown in sugarcane blackstrap molasses.
AB  - S. cerevisiae was grown in a blackstrap molasses containing medium in batch and
      fed-batch cultures. The following parameters were varied: pH (from 4.0 to 6.5),
      dissolved oxygen (DO) (from 0 to 5.0 mg O2 L-1) and sucrose feeding rate. When
      glucose concentration (S) was higher than 0.5 g L-1 a reduction in the specific
      invertase activity of intact cells (v) and an oscillatory behavior of v values
      during fermentation were observed. Both the invertase reduction and the
      oscillatory behavior of v values could be related to the glucose inhibitory
      effect on invertase biosynthesis. The best culture conditions for attaining S.
      cerevisiae cells suitable for invertase production were: temperature = 30 degrees
      C; pH = 5.0; DO = 3.3 mg O2 L-1; (S) = 0.5 g L-1 and sucrose added into the
      fermenter according to the equations: (V-Vo) = t2/16 or (V - Vo) = (Vf -
      Vo).(e0.6t-1)/10.

PMID- 7576462
TI  - Sequence of the gene encoding the 16S rRNA of the beer spoilage organism
      Megasphaera cerevisiae.
AB  - The 16S ribosomal RNA gene from the beer-spoilage organism, Megasphaera
      cerevisiae was polymerase chain reaction (PCR)-amplified and sequenced. Analysis
      confirmed the phylogenetic position of M. cerevisiae as a sister taxon of
      Megasphaera elsdenii, within the obligately anaerobic, Gram-negative cocci. The
      sequence obtained should facilitate the development of DNA probes for early
      detection of this spoilage organism.

PMID- 7576464
TI  - Rapid identification of elaiophylin and geldanamycin in Streptomyces fermentation
      broths using CPC coupled with a photodiode array detector and LC-MS
      methodologies.
AB  - During the course of screening microbial broth extracts in various high through
      put bioassays (eg receptor binding or enzyme inhibition), several actinomycete
      cultures were discovered to produce active metabolites. The natural products
      elaiophylin and/or geldanamycin are produced by several Streptomyces
      violaceusniger strains, and the bioactivity of the extracts from these cultures
      was frequently associated with the fractions containing these metabolites. CPC
      coupled to a photodiode array detector and LC-MS techniques were applied to these
      broth extracts to ascertain rapidly when these natural products were present.
      These methodologies allowed us to identify the metabolites quickly in the crude
      extract, and the application demonstrated further the utility of CPC-photodiode
      array detection and LC-MS as powerful, initial analytical tools in analyses of
      the complex metabolite profiles produced by microorganisms.

PMID- 7576466
TI  - Industrial yeast strain improvement: construction of a highly flocculent yeast
      with a killer character by protoplast fusion.
AB  - Conditions were optimized for rapid release and improved regeneration of
      protoplasts of Saccharomyces cerevisiae NCIM 3458. Rapid protoplast release was
      also obtained with representatives of several other yeast genera under the
      modified conditions of treatment. The application of the procedure in
      construction of a highly flocculent Saccharomyces cerevisiae with a killer
      character is described. Fusion was effected between UV-killed protoplasts of S.
      cerevisiae NCIM 3578 with a killer character and live protoplasts of the highly
      flocculent S. cerevisiae NCIM 3528 in the presence of polyethylene glycol (PEG)
      6000. Fusants were selected using benomyl resistance as marker, the killer toxin
      producer rather than the highly flocculent yeast being resistant to the fungicide
      at a concentration of 100 micrograms ml-1. Fusants were also characterized by
      their DNA contents, capacity for ethanolic fermentation of molasses sugar and
      levels of invertase, alcohol dehydrogenase and pyruvate decarboxylase activities.

PMID- 7576465
TI  - Use of polymerase chain reaction (PCR) fingerprinting to differentiate bacteria
      for microbial products screening.
AB  - PCR fingerprinting offers a practical molecular means to quickly and reliably
      differentiate bacteria for microbial products screening. A combination of low
      resolution and high resolution PCR fingerprinting provides a hierarchical system
      which allows the discrimination of bacteria at species and subspecies level
      within 7 h. DNA was extracted from cells by incubating them in water at 95
      degrees C for 30 min. A sample of 1 microliter of the cell-free aqueous extract
      then was used as a source of template DNA in the PCR. The PCR products were
      separated by electrophoresis on an acrylamide gel and visualized by ethidium
      bromide staining. The band patterns generated for each different culture were
      unique, reproducible, and independent of cultivation conditions. Band patterns
      may be compared visually or by using imaging and pattern matching software. In
      our laboratory, bacteria such as actinomycetes, Gram-negative and Gram-positive
      soil eubacteria, and photosynthetic non-sulfur bacteria have been differentiated
      using PCR fingerprinting.

PMID- 7576467
TI  - Blood transfusion as a risk factor for death in stage III and IV operative
      laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study
      Group.
AB  - OBJECTIVE: To evaluate the role of a blood transfusion in a patient population
      with head and neck cancer that was treated with combined therapy (surgery and
      radiation). DESIGN: Retrospective, nonrandomized end point study. Univariate and
      multivariate analysis of 24 variables, including transfusion status. SETTING: The
      Veterans Affairs Cooperative Study (Cooperative Studies Program 268). PATIENTS:
      Patients in the surgical arm of the study (166 patients) underwent surgery and
      postoperative radiation therapy for advanced (stage III and IV) laryngeal cancer.
      MAIN OUTCOME MEASURES: Identification of variables related to patient time to
      death. RESULTS: The univariate analysis identified age, clinical N (lymph node)
      class, primary tumor site, number of pathologically positive lymph nodes,
      extracapsular spread, pretreatment screening hematocrit, hematocrit and albumin
      level at 1 month after treatment, intraoperative fluids and units of blood, and
      total units of blood as significant (P < .05). The stepwise multivariate models
      identified independent significance in clinical and pathologic node status,
      hematocrits at both screening and 1 month, extracapsular spread, albumin level at
      1 month, age, and primary site. The position of each variable within the
      individual regression models varied. CONCLUSIONS: Clinical N class or pathologic
      node status occupied the first position of predictive significance in all models.
      Blood transfusion status never retained independent significance in any
      multivariate assessment.

PMID- 7576468
TI  - Patterns of recurrence after carbon dioxide laser excision of intraoral squamous
      cell carcinoma.
AB  - OBJECTIVE: To examine retrospectively consecutive patients treated with carbon
      dioxide laser excision of intraoral squamous cell carcinoma for the patterns of
      recurrence based on the location of the initial primary tumor and on the tumor
      stage. DESIGN: Retrospective chart review. SETTING: Tertiary care center
      including a university hospital and a Veterans Affairs Medical Center. PROCEDURES
      AND PATIENTS: Sixty-one procedures performed on 51 consecutive patients. The only
      patients not included were three who were unavailable for follow-up. The average
      follow-up was 32 months. If the patients whose follow-up was limited because of
      death are excluded, the average follow-up was 40 months. MAIN OUTCOME MEASURES:
      Incidence of recurrence, time to recurrence, development of second intraoral
      primary lesions or pulmonary metastases, and cause of death. RESULTS: A nearly
      equal incidence of recurrence irrespective of site of lesion (tongue, 42%; floor
      of mouth, 40%; and other oral cavity sites, 45%). Determinate survival differed
      by stage. Patients with T1 lesions showed a determinate survival rate of 80%;
      those with T2 or T3 lesions had a determinate survival rate of 57%; and those
      treated for recurrent disease had a determinate survival rate of 44%.
      CONCLUSIONS: Carbon dioxide laser excision of intraoral squamous cell carcinoma
      is a useful, advantageous method, but it appears to offer no advantage for
      recurrence over standard methods. Appropriate management of neck disease in
      patients with intraoral squamous cell carcinoma must be carefully considered.
      Patients with this potentially aggressive form of cancer deserve long-term follow
      up.

PMID- 7576469
TI  - Prognostic significance of skin involvement from mucosal tumors of the head and
      neck.
AB  - OBJECTIVE: To examine the hypothesis that skin involvement from mucosal squamous
      cell carcinoma of the head and neck is a prognostic indicator of a poor outcome.
      DESIGN: Retrospective review of cases and statistical assessment of median
      survival times. PATIENTS: Patients with mucosal squamous cell carcinoma of the
      head and neck. Fifteen patients had direct skin extension and 11 patients had
      intradermal lymphatic spread. SETTING: University medical center. RESULTS: Direct
      skin involvement was a prognostic sign of poor outcome but was less ominous than
      skin involvement by intradermal lymphatic spread. The patients with direct
      involvement had a 7-month median survival; those with lymphatic spread had a 3
      month median survival. At 3 years, all but one patient had died. Involvement of
      facial skin was better prognostically for duration of survival than was
      involvement of neck skin. Surgical resection of the involved skin in half of the
      patients extended palliation 20 months beyond the median survival of the other
      patients. CONCLUSIONS: Skin involvement from mucosal squamous cell carcinoma of
      the head and neck indicates a poor prognosis, but resection offers short-term
      palliation.

PMID- 7576470
TI  - Percutaneous endoscopic gastrostomy. A useful tool for the otolaryngologist-head
      and neck surgeon.
AB  - OBJECTIVE: To review our series of percutaneous endoscopic gastrostomy (PEG) tube
      placement by the Division of Otolaryngology. DESIGN: Charts from a total of 29
      patients were reviewed; 23 patients with head and neck cancer and six patients
      with chronic aspiration. INTERVENTIONS: Placement of a PEG tube and other
      associated procedures, including primary tumor resection, tracheostomy, and
      surgical endoscopy. MAIN OUTCOME MEASURES: The feasibility, morbidity, and
      mortality of PEGs performed at the time of the primary surgical procedure
      compared with those being performed with a minor procedure. RESULTS: In almost
      all cases, the PEG was performed in conjunction with another procedure requiring
      general anesthesia, thereby decreasing the total number of procedure days.
      Morbidity and mortality were absent for all patients in whom PEG was performed.
      CONCLUSIONS: When properly applied, PEG can be performed by the otolaryngologist
      head and neck surgeon with minimal or no morbidity at the time of staging or
      definitive procedure. Thus, the PEG can be of great benefit in patients with head
      and neck cancer.

PMID- 7576471
TI  - Outcome and complications of extended cranial-base resection requiring
      microvascular free-tissue transfer.
AB  - OBJECTIVES: To determine the complications of extensive cranial-base resection
      requiring free-tissue transfer (FTT) and the effect of these resections on local
      control and survival among patients with malignant neoplasms of the skull base.
      BACKGROUND: Before the advent of FTT, cranial-base surgery was often limited by
      our inability to adequately repair defects comprising communication between the
      central nervous system and upper aerodigestive tract. The use of FTT in cranial
      base resections was therefore assessed to determine whether the improved
      procedure (ie, extensive resections) would improve local control and prolong
      survival. DESIGN: A retrospective review of 39 consecutive craniofacial
      resections with FTT reconstruction in patients with malignant neoplasms involving
      the cranial base. PATIENTS: All 39 patients had malignant neoplasms, including 20
      squamous cell carcinomas, eight basal cell carcinomas, two melanomas, two
      neuroendocrine carcinomas, two adenoid cystic carcinomas, and various other
      malignant neoplasms. Resections involved the anterior, middle, or posterior
      cranial fossa in 19 patients (49%), 10 patients (26%), and three patients (8%) of
      cases, respectively. The remaining seven surgeries (18%) involved resection of
      more than one of these cranial base sites. RESULTS: Early (< 14 days after
      surgery) complications occurred in 14 (36%) of 39 patients. Major complications
      included failure of microvascular anastomosis (n = 1), pneumonitis (n = 3),
      perioperative myocardial infarction (n = 1), and cerebrovascular accident (n =
      1). The microvascular anastomosis failure was promptly treated with surgical
      intervention. Two patients (5%) experienced late postoperative complications; one
      had cellulitis at the donor site, and the other had pneumonitis. No perioperative
      deaths or complications such as meningitis, epidural abscess, or tension
      pneumocephalus occurred. The 2-year disease-specific survival rate was 55%, and
      the 2-year local control rate, 49%; both were determined by the Kaplan-Meier
      method. The nine patients who died of their disease had a median survival of 9
      months. Log-rank testing showed that pathologically positive margins and
      transdural pathology were the most significant predictors of local recurrence and
      death of disease. CONCLUSIONS: Contemporary surgical approaches provide an
      opportunity for wide surgical excision of dura and skull-base structures that
      normally separate the intracranial and extracranial cavities. These major skull
      base resections can be reconstructed safely and effectively with FTT. Patients
      with malignant neoplasms of the dura and skull base should be approached with the
      understanding that transdural disease portends an increased risk of local
      recurrence and death of disease.

PMID- 7576472
TI  - Thyroid carcinoma in children and adolescents.
AB  - OBJECTIVES: To categorize the clinical presentation of thyroid carcinoma in the
      pediatric and adolescent population and to present a philosophy of surgical
      management based on oncologic principles. RESULTS: Over half these children with
      thyroid carcinoma (55%) presented with an asymptomatic thyroid mass. Twelve of 26
      patients presented with lymphatic metastasis. There were no recurrences in any
      patient when the neck disease was treated with cervical lymphadenectomy or when
      the patient received postoperative radioablative therapy. CONCLUSIONS: The
      prognosis is excellent even with more extensive disease in children. Total
      thyroidectomy along with selective neck dissection for regional metastatic
      disease is recommended for thyroid carcinoma. This is followed by nuclear
      scintigraphy with subsequent radioablation for residual or recurrent disease and
      thyroid suppression and/or replacement.

PMID- 7576473
TI  - HER-2/neu oncogene characterization in head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To characterize the HER-2/neu oncogene in head and neck squamous cell
      carcinoma (HNSCC) cell lines and tumor tissue specimens. DESIGN: Molecular
      analysis of HER-2/neu oncogene amplification and expression in HNSCC cell lines
      by Southern, Northern, and Western blot techniques, and HER-2/neu oncoprotein
      expression in HNSCC tumor tissue sections by immunohistochemical analysis.
      SPECIMENS: Eleven HNSCC cell lines, eight paired samples of frozen HNSCC tumor
      tissue specimens and adjacent nonmalignant mucosa, and 38 paraffin-embedded
      slides derived from HNSCC tumor specimens (including those from which the cell
      lines were derived) were analyzed. RESULTS: Southern blot analysis showed twofold
      HER-2/neu gene amplification in two (18%) of the 11 HNSCC cell lines, MDA-1386
      and Tu-167. Northern blot analysis showed messenger RNA overexpression in the
      same two cell lines, and to a lesser degree in MDA-1483. Western blot analysis
      showed high levels of HER-2/neu oncoprotein expression in two (18%) of the 11
      cell lines (MDA-1386 and Tu-167), a moderate level of protein expression in one
      cell line (9%) (MDA-1483), and low levels of protein expression in eight cell
      lines (73%). Some HER-2/neu protein expression was seen in all of the HNSCC cell
      lines. Immunohistochemical analysis of the tumor tissue sections from which the
      cell lines were derived corroborated the Western blot results. Western blot
      analysis of frozen primary tumor specimens showed HER-2/neu oncoprotein
      overexpression in two (25%) of eight specimens. Immunohistochemical analysis
      showed high levels of protein expression in six (16%) of the 38 tumor tissue
      slides, moderate levels in 12 (31%), and low levels in 20 (53%). CONCLUSIONS: The
      HER-2/neu oncogene is overexpressed in a subset of HNSCC tumors and cell lines.
      The results from Western blot and immunohistochemical analyses underscore a
      variable HER2/neu oncoprotein expression in HNSCC. Gene amplification was
      observed in a few of the cell lines, suggesting a potential mechanism of
      oncoprotein overexpression. Messenger RNA overexpression, however, can be seen in
      the absence of gene amplification, indicating that transcriptional or
      posttranscriptional control mechanisms must be involved. Further studies are
      indicated to determine the biologic role of HER-2/neu expression in the clinical
      progression of these lesions and to further define the molecular basis regulating
      its expression.

PMID- 7576474
TI  - Interferon gamma enhances lymphokine-activated killer cell adhesion but not lysis
      of head and neck squamous cell carcinoma.
AB  - OBJECTIVES: To determine if treatment with recombinant human interferon gamma
      (rHuIFN-gamma) increases the adhesion to, and lysis of, head and neck squamous
      cell carcinoma (SCC) cells by lymphokine-activated killer (LAK) and peripheral
      blood mononuclear (PBM) effector cells in vitro and to evaluate the role of cell
      surface adhesion molecules in these processes. DESIGN: Two human SCC cell lines,
      JHU-020-SCC and JHU-022-SCC, were used. Lymphokine-activated killer cells were
      generated by interleukin-2 stimulation of PBM cells obtained from the
      hemapheresis blood donor packs of healthy individuals. Adhesion assays were
      performed to assess the level of binding of both effector populations to SCC
      cells, which were treated with either fresh media or rHuIFN-gamma (100 U/mL).
      Binding was measured by flow cytometric detection of effector cells labeled with
      fluorescein-conjugated anti-CD45 monoclonal antibody. Monoclonal antibodies to
      the cell adhesion molecules HLA-DR, lymphocyte function-associated antigen 1, and
      intercellular adhesion molecule 1 were used in blocking experiments to determine
      their contribution to the process of effector-SCC cell adhesion. Cytotoxicity
      experiments were performed using a colorimetric assay to determine the cytotoxic
      response generated by LAK and PBM cells against SCC cells, with and without prior
      rHuIFN-gamma treatment of the tumor cells. MAIN OUTCOME MEASURES: Effector cell
      binding level and percent cytotoxicity of SCC cells. RESULTS: Recombinant human
      interferon gamma treatment of JHU-020-SCC cells resulted in increased adhesion to
      both LAK cells and PBM cells (P < .001). The presence of anti-lymphocyte function
      associated antigen 1 antibody resulted in elimination of the enhanced adhesion
      seen with rHuIFN-gamma pretreatment of SCC cells (P =.03), but antibody to
      intercellular adhesion molecule 1 and HLA-DR did not reduce the level of effector
      binding. The greatest cytotoxic response against both JHU-020-SCC and JHU-022-SCC
      was seen with LAK cells (P < or = .001). Pretreatment of tumor targets by rHuIFN
      gamma (100 U/mL) resulted in no enhancement of cytotoxic response by either LAK
      or PBM cells; at the effector-target ratio of 30:1, there was a significant
      decrease in LAK cell-mediated cytotoxic response against rHuIFN-gamma-treated SCC
      cells (P < or = .02). CONCLUSIONS: Recombinant human interferon gamma treatment
      of head and neck SCC cells does increase binding of both LAK cells and PBM cells
      to tumor cells, in part via the lymphocyte function-associated antigen 1 ligand
      mechanism. The cytotoxic effect mediated by LAK cells against head and neck SCC
      cells is reduced after rHuIFN-gamma treatment, suggesting that the activity of
      this cytokine may be more important in regulating antigen-specific cytotoxic
      response mediated by cytotoxic T-lymphocytes.

PMID- 7576477
TI  - A reappraisal of the squamous cell carcinoma antigen as a tumor marker in head
      and neck cancer.
AB  - OBJECTIVE: To analyze serial measurements of squamous cell carcinoma antigen
      (SCCAg) to determine its prognostic significance in squamous cell carcinoma of
      the head and neck (SCCHN). DESIGN: Retrospective analysis of serial SCCAg
      measurements in 75 patients with squamous cell carcinoma of the head and neck.
      Serum samples were obtained preoperatively and at postoperative intervals ranging
      from 1 week to 36 months. Serum SCCAg levels were determined by radioimmunoassay.
      SETTING: Oncologic head and neck practice at a tertiary referral hospital.
      PATIENTS: Tumor Registry data of 75 consecutive patients with at least three
      postoperative SCCAg determinations were reviewed to provide equal numbers of
      patients with and without recurrent disease. All patients who remained disease
      free were followed up for at least 2 years. All patients were previously
      untreated and underwent surgical therapy. MAIN OUTCOME MEASURES: Association of
      postoperative SCCAg levels and 2-year disease-free survival. RESULTS: No
      differences in preoperative levels were noted, but SCCAg levels predicted 2-year
      disease-free survival at 6, 9, and 12 months after surgery. The ratio of post
      operative SCCAg levels to preoperative and early post-operative levels also
      provided prognostic information. CONCLUSIONS: Serial measurements of SCCAg
      postoperatively in patients with head and neck cancer predict outcome and may
      allow for earlier detection of recurrent disease. Further studies are needed to
      determine if earlier detection can be translated into improved survival.

PMID- 7576475
TI  - Adhesion of head and neck squamous cell carcinoma to endothelial cells. The
      missing links.
AB  - OBJECTIVES: To examine the direct adhesion of head and neck squamous cell
      carcinoma (HNSCC) cells to basal and cytokine-activated human endothelial cells
      and to determine the cell adhesion molecules (CAMs) that mediate binding under
      these two conditions. DESIGN: Using an established model of tumor metastasis, the
      adhesion of four HNSCC cell lines to human umbilical vein endothelial cell
      (HUVEC) monolayers was examined, with and without pretreatment of HUVEC with
      tumor necrosis factor alpha (TNF-alpha). Surface CAM expression of HNSCC and
      HUVEC was determined by flow cytometry, and the results were used to direct
      studies of adhesion blocking using monoclonal antibodies. The contribution of
      various CAM to HNSCC binding of basal and cytokine-activated human endothelial
      cells in vitro was established. MAIN OUTCOME MEASURES: Adhesion of HNSCC to HUVEC
      monolayers was determined by a sodium chromate Cr 51-labeling assay in the
      presence or absence of monoclonal antibodies directed against specific CAMs.
      RESULTS: Four HNSCC cell lines were shown by flow cytometry to constitutively
      express the following CAMs: intercellular CAM-1, CD44, lymphocyte function
      associated antigen-3, integrin chains alpha 6 and beta 1, and sialyl Lewis(x). No
      cell lines expressed lymphocyte function-associated antigen-1 or the integrin
      subunit alpha 4. Adhesion of JHU-011-SCC to TNF-alpha-activated HUVEC was
      enhanced above the untreated level in a time-dependent manner, with maximal
      adhesion at 12 hours. This increase correlated with endothelial-selectin
      expression by HUVEC and HNSCC expression of its ligand sialyl Lewis(x).
      Monoclonal antibody to sialyl Lewis(x) blocked the increased adhesion to TNF
      alpha-activated HUVEC in two of four HNSCC cell lines. Monoclonal antibody to the
      alpha 6 integrin reduced binding to TNF-alpha-activated and non-activated HUVEC
      and to subendothelial matrix, but not to fibronectin. CONCLUSIONS: Studies of
      four HNSCC cell lines disclosed a consistent and distinctive pattern of adhesion
      molecule expression. The alpha 6 integrin subunit may be involved in direct
      adhesion to nonactivate and cytokine-activated endothelial cells or to laminin
      present on the endothelial surface. Sialyl Lewis(x) was more specifically
      involved in the increased adhesion to cytokine-activated HUVEC. This suggests
      that the sialyl Lewis(x)-endothelial-selectin ligand interaction may be important
      in facilitating HNSCC adhesion during metastasis to sites of active or chronic
      inflammation in vivo.

PMID- 7576476
TI  - Native cellular fluorescence of neoplastic upper aerodigestive mucosa.
AB  - OBJECTIVE: To identify alterations in the biochemical composition and
      histoarchitectural structure of the lining epithelium that signal malignant
      transformation in carcinogen-exposed upper aerodigestive mucosa by quantitation
      of native cellular fluorescent properties. DESIGN: Case series. SETTING: Head and
      Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New
      York, NY. PATIENTS AND METHODS: Thirty-one patients with previously untreated
      mucosal neoplasias of the oral cavity and pharynx were studied by means of a hand
      held fiberoptic probe attached to a xenon lamp-based fluorescent spectrometer.
      Fluorescence analyses of the lesions and contralateral normal sites were
      performed in each patient on the basis of specific emission and excitation
      wavelengths. Differences between normal tissue and neoplastic mucosa were tested
      for statistical significance by paired t test and Hotelling's T2 test. RESULTS:
      The ratios of fluorescence intensities of neoplastic mucosa and contralateral
      normal sites were significantly different in three of the four fluorescence scans
      (excitation of 300 nm and emission of 320 to 580 nm; excitation of 340 nm and
      emission of 360 to 660 nm; and excitation of 200 to 360 nm and emission of 380
      nm) when analyzed individually (P < .05). The ratios in the scans with excitation
      of 240 to 430 nm and emission of 450 nm were not significantly different. All
      four scans, when analyzed together, demonstrated significant differences between
      normal and neoplastic tissues (P < .01). CONCLUSIONS: Neoplastic mucosa of the
      upper aerodigestive tract within an individual patient will express native
      cellular fluorescent properties in vivo that differ from those of normal upper
      aerodigestive epithelia. This may represent a noninvasive screening method for
      head and neck squamous cell cancers.

PMID- 7576478
TI  - Nasopharyngeal carcinoma with dermatomyositis. Analysis of 12 cases.
AB  - OBJECTIVES: To evaluate the incidence rate of nasopharyngeal carcinoma with
      dermatomyositis, the influence of dermatomyositis on clinical course, and
      complications and survival of patients with nasopharyngeal carcinoma after
      radiotherapy. DESIGN: A retrospective study of 12 patients with nasopharyngeal
      carcinoma associated with dermatomyositis, with a maximum follow-up of 228
      months. SETTING: Academic tertiary referral center. PATIENTS: There were 6441 new
      patients with nasopharyngeal carcinoma who were seen at the National Taiwan
      University Hospital, Taipei, during the period from 1970 through 1993. Twelve
      patients were found to have dermatomyositis. MAIN OUTCOME MEASURE: Clinical
      manifestations of nasopharyngeal carcinoma with dermatomyositis. RESULTS: Twenty
      seven (26%) of 104 patients with dermatomyositis had an associated malignancy.
      Twelve of these patients were diagnosed as having nasopharyngeal carcinoma. The
      typical skin manifestation of dermatomyositis was found in all 12 patients.
      Myopathy occurred in 10 patients. Three patients died of recurrence of
      nasopharyngeal carcinoma, one died of a second malignancy, one died of upper
      gastrointestinal bleeding, and one became unavailable for follow-up. The other
      six patients have had disease-free survival, with a mean follow-up period of
      100.5 months (range, 5 to 228 months). The 1-year survival rate was 83.8%, and
      the 5-year survival rate was 69.4%. CONCLUSIONS: In Taiwan, dermatomyositis is
      associated with an increased incidence rate of nasopharyngeal carcinoma. A search
      for nasopharyngeal carcinoma in patients with dermatomyositis should be performed
      in areas prevalent for nasopharyngeal carcinoma. If present, nasopharyngeal
      carcinoma can precede, occur concurrently with, or follow the diagnosis of
      dermatomyositis. Treatment of nasopharyngeal carcinoma may affect myositic or
      cutaneous disease. The prognosis and survival rates of nasopharyngeal carcinoma
      remained unaffected by dermatomyositis. No complications were noted owing to the
      radiotherapy used to treat dermatomyositis.

PMID- 7576479
TI  - Laryngeal oncocytic cystadenomas. Eight cases and a literature review.
AB  - OBJECTIVE: To describe an uncommon clinical entity, laryngeal oncocytic salivary
      adenomas. BACKGROUND: While the nomenclature of these lesions may differ
      depending on their histologic appearance, these tumors are all generally part of
      a spectrum of clinically benign cystic and papillary lesions derived from
      oncocytic metaplasia and hyperplasia of minor salivary ducts. DESIGN: Eight cases
      of laryngeal oncocytic lesions collected from two institutions. Further clinical
      background and follow-up data were obtained on five of eight patients. RESULTS:
      Patients were mostly in their seventh and eighth decades of life, and all who
      were questioned had smoking histories. Hoarseness was a common presenting
      complaint, and all patients had polypoid laryngeal masses. One patient presented
      with progressive upper airway obstruction, which was ultimately fatal; the
      laryngeal oncocytic cystadenoma was diagnosed in this case during postmortem
      examination. The laryngeal lesions were predominantly supraglottic.
      Histologically, they consisted of oncocytic metaplasia of the minor salivary
      ducts, cystic dilation, and papillary and microcystic hyperplasia. No recurrences
      were seen in those patients with follow-up (four of eight). CONCLUSIONS:
      Laryngeal oncocytic lesions usually present as supraglottic masses in older
      patients. While they are oncologically benign and nonrecurring after endoscopic
      removal, they may occasionally be the cause of significant upper airway
      obstruction.

PMID- 7576480
TI  - Expanded polytef for reconstructing postparotidectomy defects and preventing
      Frey's syndrome.
AB  - An expanded polytef (polytetrafluoroethylene [ePTFE]) soft-tissue patch was used
      in nine patients to reconstruct postparotidectomy defects and prevent Frey's
      syndrome. All nine cases were constructed primarily using either a 1- or 2-mm
      thick patch depending on the depth of the defect. All nine patients achieved
      excellent, nearly normal contour that approximates the uninvolved side. None
      complained of Frey's syndrome. Average follow-up to date is 12 months.

PMID- 7576483
TI  - Pathologic quiz case 1. Adenoid cystic carcinoma (ACC) of the ethmoid sinus.

PMID- 7576482
TI  - The risk of nasal osteotomies after ethmoid sinus surgery.
AB  - OBJECTIVE: To assess whether there is an increased risk of osteotomies causing
      fractures that extend into the orbit or cranial base in patients who undergo
      ethmoid sinus surgery. DESIGN: Anatomic investigation in a cadaver model.
      METHODS: Twenty-eight medial and lateral osteotomies were performed in 14 fresh
      frozen cadaver heads after bilateral sphenoethmoidectomies (endoscopic technique,
      n = 26; external technique, n = 2). Anatomic examination performed by inspection
      after removal of dorsal nasal skin followed by rigid endoscopic intranasal
      examination. RESULTS: Complete osteotomies were obtained in every case. There
      were no major comminutions along the osteotomies, but there was a 25% rate of
      minor comminutions. In no case did fractures extend into either the orbit or the
      base of the skull. In every case, the path of the osteotome was separated from
      the ethmoid surgical cavity by a relatively thick buttress of bone composed of
      the anterior lacrimal crest and the ascending process of the maxilla. The
      enlarged maxillary ostia created by the sinus surgery was not altered by the
      osteotomies or by dorsal narrowing. CONCLUSIONS: Nasal osteotomies can be
      performed with minimal risk of comminution or uncontrolled extension of the
      fracture lines following extensive ethmoid and sphenoid sinus surgery. These
      findings may not apply in patients with preexisting injuries or when osteotomies
      do not preserve the triangular nasal buttress.

PMID- 7576481
TI  - Suprahyoid and inferior constrictor release for laryngeal lowering.
AB  - OBJECTIVE: To quantify accurately the suprahyoid and inferior constrictor
      releases, which are used to decrease tension across a tracheal anastomosis
      performed after tracheal resection. DESIGN: Intraoperative tension measurements
      at 0.5-cm intervals of the released laryngotracheal unit were obtained using a
      spring balance after division of the trachea. SUBJECTS: A selected series of
      eight patients undergoing total laryngectomy for laryngeal carcinoma, excluding
      those with cervical soft-tissue involvement, tongue-base involvement, or a
      history of radiation therapy to the head and neck. RESULTS: The suprahyoid and
      inferior constrictor releases together permit a tension-free, inferior
      displacement of 2 cm. The suprahyoid release alone permits an inferior
      laryngotracheal displacement of 3.5 cm without exceeding the critical,
      anastomotic failure tension of 1700 g. Using the releasing techniques together
      permits inferior displacement of 4 cm without notably exceeding this critical
      tension. CONCLUSIONS: The closure of 2-cm defects without a releasing procedure
      is supported by this study. Larger defects of 3.5 cm, and occasionally 4 cm, can
      be closed safely without exceeding the critical tension level using a suprahyoid
      release. This study supports the use of the suprahyoid and inferior constrictor
      releases together for the uncomplicated closure of 4-cm defects.

PMID- 7576484
TI  - Pathologic quiz case 2. Ossifying fibromyxoid tumor.

PMID- 7576485
TI  - The Merck Frosst Award Lecture 1994/La conference Merck Frosst 1994. Calnexin: a
      molecular chaperone with a taste for carbohydrate.
AB  - Calnexin is an integral membrane protein of the endoplasmic reticulum (ER) that
      binds transiently to a wide array of newly synthesized membrane and secretory
      proteins. It also exhibits prolonged binding to misfolded or incompletely folded
      proteins. Recent studies have demonstrated that calnexin functions as a molecular
      chaperone to facilitate the folding and assembly of proteins in the ER. It is
      also a component of the quality control system that prevents proteins from
      progressing along the secretory pathway until they have acquired proper tertiary
      or quaternary structure. Most proteins that are translocated into the ER are
      glycosylated at Asn residues, and calnexin's interactions are almost exclusively
      restricted to proteins that possess this posttranslational modification. The
      preference for glycoproteins resides in calnexin's ability to function as a
      lectin with specificity for the Glc1Man9GlcNAc2 oligosaccharide, an early
      intermediate in the processing of Asn-linked oligosaccharides. Calnexin also has
      the capacity to bind to polypeptide segments of unfolded glycoproteins. Available
      evidence suggests that calnexin utilizes its lectin property during initial
      capture of a newly synthesized glycoprotein and that subsequent association (and
      chaperone function) is mediated through polypeptide interactions. Unlike other
      molecular chaperones that are soluble proteins, calnexin is an intrinsic
      component of the ER membrane. Its unique ability to capture unfolded
      glycoproteins through their large oligosaccharide moieties may have evolved as a
      means to overcome accessibility problems imposed by being constrained within a
      lipid bilayer.

PMID- 7576486
TI  - Signaling in new directions.
AB  - Many laboratories, using a variety of organisms, have contributed to deciphering
      the identity and the order of the components leading from ligand-bound receptor
      tyrosine kinases to various intracellular events, including changes in gene
      expression. The gaps have only been filled recently. This minireview summarizes
      the findings and points out the degree of conservation of the same pathway in
      distant organisms, both at the molecular level and in terms of the consecutive
      steps. The review also looks at points at which this pathway might be diverging
      and points onto which other pathways might be converging. These interactions are
      not always clear cut, and understanding them will be the challenge for the
      future.

PMID- 7576487
TI  - Two basic motifs of reovirus sigma 3 protein are involved in double-stranded RNA
      binding.
AB  - It has been reported that the sigma 3 protein of reovirus can exert an inhibitory
      effect on the cellular double-stranded RNA (dsRNA) activated protein kinase.
      Activation of this kinase is thought to be a general mechanism mediating a
      cellular antiviral response. This enzyme can also be activated upon transfection,
      resulting in translational inhibition of plasmid-encoded mRNAs. sigma 3 has an
      affinity for dsRNA postulated to be responsible for antikinase activity. In the
      present study, site-directed mutagenesis was performed on two basic regions
      previously suggested as dsRNA-binding motifs and the mutant sigma 3 proteins were
      then expressed in COS cells. These experiments revealed that both motifs are
      involved in sigma 3 attachment to RNA. Expression of the mutants lacking RNA
      binding capability is stimulated by coexpression of another dsRNA-binding
      protein, the E3L vaccinia virus protein. These results support a model in which
      the attachment to dsRNA is directly responsible for the trans-stimulating effect
      of sigma 3 on expression of cotransfected genes.

PMID- 7576488
TI  - Physiological role of GlpB of anaerobic glycerol-3-phosphate dehydrogenase of
      Escherichia coli.
AB  - Anaerobic sn-glycerol-3-phosphate dehydrogenase of Escherichia coli is encoded by
      an operon of three genes, glpACB. The promoter distal gene, glpB, encodes a 44
      kilodalton polypeptide that is not part of the purified soluble dehydrogenase. By
      recombinant plasmid complementation, in a strain harboring a chromosomal deletion
      of glpACB, we found that all three genes were essential for anaerobic growth on
      glycerol-3-phosphate (G3P). By isolation of inner membrane preparations we
      confirmed the cytoplasmic membrane localization of GlpB. GlpB displayed an
      electron paramagnetic resonance spectrum that suggested the presence of iron
      sulfur center(s) within GlpB. We used this spectrum to show that the center(s)
      were reduced by the artificial reductant dithionite and by the physiological
      substrate G3P but not by lactate or formate. The center(s) were oxidized by
      fumarate. These data indicated that GlpB mediates electron transfer from the
      soluble GlpAC dimer to the terminal electron acceptor fumarate via the membrane
      bound menaquinone pool.

PMID- 7576489
TI  - Platelet glutathione transport: characteristics and evidence for regulation by
      intraplatelet thiol status.
AB  - The present study demonstrates the carrier-mediated uptake of intact glutathione
      (GSH) by human platelets. Platelet GSH uptake was characterized as being Na+
      independent and saturable. The KM, apparent and Vmax, apparent for GSH uptake in
      platelet plasma membrane vesicles were 28.0 +/- 8.4 microM and 263.5 +/- 28.5
      pmol/min per mg protein, respectively. The transport was inhibited by GSH analogs
      and enhanced by KCl-induced membrane depolarization. GSH transport may be
      regulated by the intracellular thiol status, since the depletion of intraplatelet
      GSH with 100 microM 1-chloro-2,4-dinitrobenzene (CDNB) increased GSH uptake by
      approximately 40%. The KM, apparent and Vmax, apparent for GSH uptake in intact
      platelets changed from 99.5 +/- 15 microM and 42 +/- 7.5 pmol/min per 10(9)
      platelets, respectively, to 33.7 +/- 6.7 microM and 21.5 +/- 6.9 pmol/min per
      10(9) platelets, respectively, on reducing intraplatelet GSH with 100 microM
      CDNB.

PMID- 7576490
TI  - Enzymatic characterization of purified recombinant human renin.
AB  - Renin is a highly specific aspartyl protease of the renin-angiotensin system
      initially synthesized as preprorenin. Recombinant human prorenin was produced in
      cell factories from stably transfected DAMP cells, a dog epithelial cell line.
      The equivalent of 10-15 mg of recombinant human renin was secreted in the
      supernatant from each cell factory. Following a single affinity chromatography
      step using a renin inhibitor as the ligand, a 181-fold purification was achieved
      with 81% recovery of the renin activity. This highly pure recombinant enzyme
      having a specific activity of 3.44 mg angiotensin I.mg protein-1.h-1 was used for
      kinetic analysis. The kinetic parameters were determined with the natural
      substrate angiotensinogen and a tetradecapeptide substrate corresponding to the
      amino terminus of angiotensinogen, Asp1-Asn14, at their respective optimum pH of
      5.5 and 6.8. Although there was a six-fold increase in both Km and kcat values
      for the peptidic substrate (13.3 microM and 8.1 s-1, respectively), when compared
      with values for the natural substrate (2.04 microM and 1.41 s-1), the catalytic
      efficiency (0.69 microM-1.s-1) of the enzyme for both substrates was the same.
      However, the kcat/Km value with angiotensinogen at the physiological pH 7.4 was
      30% lower than that observed at the optimum pH 5.5. The recombinant human renin
      displayed similar optimum pH and kinetic parameters with angiotensinogen and the
      tetradecapeptide substrate when compared with human kidney renin.

PMID- 7576492
TI  - Hypothyroidism prolongs and increases mdx muscle precursor proliferation and
      delays myotube formation in normal and dystrophic limb muscle.
AB  - Hypothyroidism (induced by 8 weeks of oral 0.05% propylthiouracil) heightened the
      phenotype of mdx mouse dystrophin-deficient myopathy to more closely resemble
      human Duchenne muscular dystrophy. Muscle repair after crush injury to the
      tibialis anterior muscle (TA) in hypothyroid mdx mice showed decreased myotube
      formation and delayed debris removal. To investigate whether reduced muscle
      precursor cell proliferation can account for the effects of hypothyroidism on
      repair from injury, immunocytochemistry for neural cell adhesion molecule (NCAM)
      on muscle precursor cells and autoradiography to detect DNA synthesis were
      performed in control and mdx TA. The proportions of labelled polymorphonuclear
      leukocyte nuclei (PMN), myotube nuclei (MN), and total mononuclear cell nuclei
      (TLN, the majority being muscle precursors) were counted in defined areas of
      regenerating TA after 2 and 4 days recovery. MN and the numbers of activated
      satellite cell nuclei on intact fibers were counted in surviving areas. In the
      same muscle, earlier phases of regeneration were observed in areas distal than
      proximal to the injury. At 2 days of regeneration, labelled PMN were increased in
      treated compared with untreated mdx TA. In distal areas at 4 days, fewer muscle
      precursors had recently fused to myotubes in treated than in untreated mdx. In
      proximal areas 4 days (relatively late in repair), TLN data suggested that muscle
      precursor proliferation was greater in hypothyroid compared with untreated mdx
      TA. NCAM immunostaining was consistent with proliferation data and confirmed that
      there were more muscle precursors in mdx than in control regenerating muscle.
      These results suggest that hypothyroidism prolongs and increases the phase of
      replication by mdx muscle precursors and delays precursor fusion into myotubes in
      regeneration.

PMID- 7576491
TI  - Characteristics of exogenous lipid uptake by renal and intestinal brush-border
      membrane vesicles.
AB  - The transfer of radioactive phosphatidylcholine (PC*) from liposomes to rabbit
      jejunal and renal brush-border membrane vesicles (BBMVs) was measured with a fast
      sampling, rapid-filtration apparatus. PC* uptake by jejunal and renal BBMVs was
      favoured when liposomes were made from soybean phosphatidylcholine (azolectin,
      AZO), whereas PC* uptake could not be quantitatively assessed from egg yolk
      phosphatidylcholine (PC) liposomes even after a 22-h period of incubation. The
      increased turbidity of BBMV dispersion following the addition of CaCl2 or HCl to
      AZO-treated BBMVs suggested that negatively charged lipids and
      phosphatidylethanolamine are transferred during the process. These data and the
      analysis of PC*-uptake time measurements, using an algorithm simulating
      aggregation phenomena, indicated that the reaction mechanism involved liposome
      aggregation to BBMVs rather than specific lipid transfer. The constants of the
      dimerization reaction between AZO liposomes and BBMVs were evaluated to be 0.016
      +/- 0.006 min-1 for jejunal and 0.095 +/- 0.02 min-1 for renal preparations.
      IntraveSICULAR D-ASPartic acid accumulation in the presence of a NA+ gradient
      indicated that vesicles were still closed after coincubation with liposomes. In
      contrast, 70-85% of rabbit jejunal and renal Na(+)-D-glucose cotransporter
      activities were lost after overnight incubation with either AZO liposomes or
      buffered solution. Further, H(+)-ATPase activity in rabbit renal BBMVs largely
      decreased after coincubation with AZO liposomes, while brush-border membrane
      associated enzymes remained stable. These results demonstrate that coincubation
      of BBMV with liposomes of different composition may represent a useful approach
      to study the influence of lipidic environment on various membrane protein
      functions.

PMID- 7576494
TI  - Calmodulin-dependent protein kinase II is required for G1/S progression in HeLa
      cells.
AB  - Calmodulin (CaM) has been previously shown to be essential for cell cycle
      progression in eukaryotic cells, being required at the G1/S, G2/M, and metaphase
      anaphase transitions. Little is known about the the specific CaM-dependent
      enzymes that mediate Ca2+/CaM signaling to affect cell proliferation. In this
      study we show that inhibition of calmodulin kinase II (CaMKII) in HeLa cells
      using the CaMKII inhibitor KN-93 causes cell cycle arrest, demonstrating that
      CaMKII is required for cell cycle progression. Detailed analysis of arrest cells
      suggests that CaMKII is required for the initiation of DNA synthesis. Cells
      treated with KN-93 arrest with a G1 DNA content, but with elevated cyclin
      dependent histone H1 kinase activity, suggesting that CaMKII may act at a point
      very close to the onset of DNA synthesis in mammalian cells.

PMID- 7576495
TI  - Inhibition of food-borne pathogenic bacteria by bacteriocins from Lactobacillus
      gasseri.
AB  - Lactobacillus acidophilus group and a Lact. reuteri isolated from human faeces
      were examined for production of antimicrobial agents against 16 strains of six
      species of food-borne enteric pathogenic bacteria. Several strains of Lact.
      gasseri showed wide inhibitory activity against the tested bacteria. Gassericin A
      produced by Lact. gasseri LA39 was one of the most widely active bacteriocins. It
      was bactericidal without causing cell lysis.

PMID- 7576493
TI  - Vasopressin activates phospholipase D through pertussis toxin-insensitive GTP
      binding protein in aortic smooth muscle cells: function of Ca2+/calmodulin.
AB  - In the present study, we examined the effect of vasopressin (AVP) on
      phosphatidylcholine-hydrolyzing phospholipase D activity in primary cultured rat
      aortic smooth muscle cells. AVP stimulation of choline formation was dose
      dependent. The time-course was quite different from those of inositol phosphates.
      The effect of AVP on the formation of inositol phosphates (EC50 was 3 nM) was
      more potent than that on the formation of choline (EC50 was 30 nM). 12-O
      Tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC),
      stimulated the formation of choline. However, 4 alpha-phorbol 12,13-didecanoate,
      which is inactive for PKC, had little effect. Staurosporine, an inhibitor of
      protein kinases, which inhibited the TPA-induced formation of choline, had little
      effect on the AVP-induced formation of choline. Neither calphostin C, a highly
      specific PKC inhibitor, nor PKC down-regulation with TPA affected AVP-induced
      formation of choline. A combination of AVP and TPA additively stimulated the
      formation of choline. The depletion of extracellular Ca2+ by
      (ethylenebis(oxyethylenenitrilo)tetraacetic acid significantly reduced the AVP
      induced formation of choline. W-7, an antagonist of calmodulin, inhibited the AVP
      induced formation of choline in a dose-dependent manner. NaF, an activator for
      GTP-binding protein (G-protein), stimulated the formation of choline. However,
      the formation of choline by a combination of AVP and NaF was not additive.
      Pertussis toxin had little effect on the AVP-induced formation of
      choline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576496
TI  - Adhesion of different bifidobacteria strains to human enterocyte-like Caco-2
      cells and comparison with in vivo study.
AB  - The validity of the in vitro adhesion tests performed with cultured cell lines,
      was determined in this study by comparison with results obtained in vivo, in a
      previous study. To make this experiment the in vitro adhesion tests were
      performed during a long period by utilization of an appropriate medium, to
      determine the capacity of the adhered strain to colonize the intestinal tract. It
      was demonstrated that the ability of the strain to adhere and colonize the
      intestinal cell in vivo or the cultured intestinal cells in intro was similar.

PMID- 7576498
TI  - An evaluation of immunomagnetic separation for the detection of salmonellas in
      raw chicken carcasses.
AB  - Immunomagnetic separation techniques were used in the isolation of salmonella
      from raw chicken carcasses. Improved isolation rates were achieved with increased
      specificity and decreased processing time, although several technical
      difficulties remain to be addressed. Immunomagnetic separation offers significant
      potential for improvement on existing microbiological systems for the isolation
      of salmonella.

PMID- 7576499
TI  - Randomly amplified polymorphic DNA (RAPD) for rapid typing of Lactobacillus
      plantarum strains.
AB  - Randomly amplified polymorphic DNA (RAPD) has been used for rapid typing of
      Lactobacillus plantarum strains. RAPD was used with either purified chromosomal
      DNA serving as template in the polymerase chain reaction, or with crude cell
      extracts, and using a 9-mer primer with 80% G+C content. Amplified DNA was
      visualized by ethidium bromide staining after separation on agarose gels.
      Patterns from 20 Lact. plantarum strains and two Lact. pentosus strains were
      analysed using the Pearson products moment correlation coefficient (r) and the
      unweighted pair group method with arithmetic averages (UPGMA). With some
      exceptions, the two sources of template DNA gave the same clusters and
      subclusters of strains at the similarity level of 50%. About 50% of the strains
      could be individually separated from all the other tested strains. The buffer
      brand, the amount of primer and crude cell extract used in the PCR-step were
      crucial for the final pattern.

PMID- 7576500
TI  - Evaluation of the BBL Crystal Enteric/Nonfermenter kit for the identification of
      water-derived environmental Enterobacteriaceae.
AB  - The Crystal Enteric/Nonfermenter (E/NF) identification kit (Becton Dickinson
      Microbiology Systems, USA) was evaluated using water-derived bacterial isolates
      and results compared to those obtained by the API 20E system (BioMerieux, UK).
      Both the E/NF and 20E systems correctly identified 93% of the Enterobacteriaceae
      reference cultures. Both systems agreed in the identification of 64.9% of
      environmental isolates. The E/NF system gave a positive identification to 88.0%
      of isolates and the 20E to 79.5% of isolates. The principal tests which gave
      differing reactions between the two systems were arginine dihydrolase, lysine
      decarboxylase, urease and citrate utilization.

PMID- 7576501
TI  - Biogenic amine formation by poultry-associated spoilage and pathogenic bacteria.
AB  - The production of biogenic amines by 50 poultry-associated bacterial strains (25
      Pseudomonas, 13 Salmonella and 12 Listeria) was investigated on amine agar plates
      containing lysine, histidine, ornithine, phenylalanine, tryptophan and tyrosine.
      Seventy-four per cent of all the strains produced cadaverine and putrescine,
      while phenylethylamine, histamine, tyramine and tryptamine were produced by 72,
      56, 34 and 24% of strains, respectively. Different patterns of biogenic amine
      production amongst the three bacterial genera tested were apparent as well as
      amongst strains of the same genus. This study highlighted a high incidence of
      biogenic amine-producing bacterial strains associated with poultry.

PMID- 7576497
TI  - Effects of three strains of bifidobacteria on cholesterol.
AB  - To determine the validity of the hypothesis of assimilation or precipitation of
      cholesterol by Bifidobacterium species, resting cell assays and cultures were
      undertaken in TPY medium containing oxgall. With resting cell assays (pH 5),
      cholesterol was precipitated and redissolved in phosphate buffer (pH 7). At the
      end of the cultures, only part of the removed cholesterol from the culture medium
      was found in the phosphate buffer, while the missing cholesterol was in cell
      extracts. It appeared that removal of cholesterol during culturing was not solely
      due to its precipitation. It is concluded that growing bifidobacteria cells are
      able to remove cholesterol both by precipitation and assimilation.

PMID- 7576502
TI  - Quantification of the effect of substrate concentration on the conjugal transfer
      rate of the TOL plasmid in short-term batch mating experiments.
AB  - Batch mating experiments with Pseudomonas putida PAW 1 (TOL) as a donor and
      Pseudomonas aeruginosa PAO 1162 as a recipient strain were performed to quantify
      the effect of the substrate concentration in the mating medium on the observed
      plasmid transfer rate coefficient. The impact of the substrate concentration in
      the mating medium was highly correlated with the growth history of the donor
      strain. When the donor strain was harvested in exponential growth phase, no
      impact was observed; when the donor strain was taken from the stationary phase,
      however, a strong impact of the substrate concentration was measured: a 10-fold
      reduction in the substrate concentration decreased the observed plasmid transfer
      rate by 55%.

PMID- 7576504
TI  - Research note: detection of Salmonella in minced meat by the polymerase chain
      reaction method.
AB  - A specific PCR assay was used to detect Salmonella in enriched broths of 48
      natural samples of minced pork and 48 natural samples of minced beef. By
      comparison with a routine culture method, the sensitivity of the PCR method was
      estimated to be 92% and the specificity of the PCR method was estimated to be
      99%. The sensitivity of the culture method was estimated to be 50% in this study.

PMID- 7576503
TI  - Enhanced biodegradation and emulsification of crude oil and hyperproduction of
      biosurfactants by a gamma ray-induced mutant of Pseudomonas aeruginosa.
AB  - A gamma ray-induced mutant of Pseudomonas aeruginosa strain S8, capable of
      hyperproduction of biosurfactant from hydrocarbons, was isolated and named as EBN
      8. The mutant showed 3-4 times more hydrocarbon emulsification/conversion as
      compared to the parent when grown on Khaskheli crude oil in minimal medium.
      Enhanced biosurfactant production and hydrocarbon utilization by the mutant was
      also observed during growth on heptadecane in minimal medium as indicated by
      emulsion index and surface tension of cell-free culture broth. Using heptadecane
      as carbon and energy source, time course for the growth (cfu ml-1) and
      biosurfactant production were compared for both parent and mutant. These studies
      were carried out for 24 d at 30 +/- 2 degrees C and for 20 d at 37 degrees C.
      Growth of EBN-8 was much faster compared to the parent as well as being 2-3 times
      more hyperproductive.

PMID- 7576506
TI  - Electrophoretic karyotyping of the yeast genus Torulaspora.
AB  - Karyotypes of yeast strains in the genus Torulaspora were determined by pulse
      field gel electrophoresis and compared with those of the related genus
      Zygosaccharomyces. The DNA bands ranged from 800 to 1600 kb in T. delbrueckii and
      800 to 2000 kb in both T. globosa and T. pretoriensis and those numbers were
      about six in the three species. The chromosomes of Torulaspora strains comprised
      relatively smaller size of DNAs than Zygosaccharomyces strains.

PMID- 7576505
TI  - Expression of lactococcin A and pediocin PA-1 in heterologous hosts.
AB  - Pediocin PA-1 production, immunity and secretion are specified by a cluster of
      four genes in Pediococcus acidilactici PAC1.0. The production by, secretion of,
      and immunity to lactococcin A of Lactococcus lactis are also determined by four
      genes. Here, expression of the pediocin operon in Lactococcus lactis is reported,
      which could only be achieved by placing it under control of a lactococcal
      promoter. Expression of the lactococcin A operon in Pediococcus is also
      described: recombinant clones of Pediococcus were obtained that produced and
      secreted both active pediocin PA-1 and lactococcin A.

PMID- 7576507
TI  - Survival of Campylobacter jejuni in foods and comparison with a predictive model.
AB  - Campylobacter jejuni was inoculated into a range of raw and cooked foods and
      survival determined during storage at 2 degrees, 10 degrees and 20 degrees C for
      up to 56 d. To facilitate easy enumeration, two antibiotic-resistant strains of
      Camp. jejuni, which had similar survival characteristics to the parent strain,
      were used. Campylobacter jejuni survived for longer at lower temperatures in all
      foods and inactivation was most rapid in pate. There was generally good agreement
      between the survival data and predictions from a Camp. jejuni survival model
      (Food MicroModel).

PMID- 7576508
TI  - Rapid mitochondrial probes for analysis of polymorphisms in Fusarium oxysporum
      special forms.
AB  - A method is described for the production of simple mitochondrial DNA probes from
      filamentous fungi for the partial characterization of mitochondrial DNA without
      the need for cloning, gradient centrifugation or PCR amplification. A probe
      (P449) consisting of a 3.38 kb mitochondrial fragment from an isolate of Fusarium
      oxysporum special form cubense was used to determine RFLPs in restriction digests
      of total DNA from 28 isolates of F. oxysporum from a variety of hosts and
      locations. The probe showed mtDNA polymorphisms within and between different
      special forms.

PMID- 7576509
TI  - Cetobacterium ceti gen. nov., sp. nov., a new gram-negative obligate anaerobe
      from sea mammals.
AB  - Phenotypic and phylogenetic studies were performed on a Gram-negative obligately
      anaerobic rod-shaped bacterium isolated from two sea mammals. 16S rRNA gene
      sequence analysis demonstrated the bacterium represents a hitherto unknown line
      of descent peripherally associated to the fusobacteria and low G+C relatives.
      Based on the result of the phylogenetic analysis and phenotypic criteria, it is
      proposed that the bacterium should be assigned to a new genus, Cetobacterium ceti
      gen. nov., sp. nov. The type strain of Cetobacterium ceti sp. nov. is NCFB 3026.

PMID- 7576510
TI  - Detection of coliphages and enteroviruses in sewage and aerosol from an activated
      sludge wastewater treatment plant.
AB  - Coliphages and enteroviruses were monitored over 12 months in sewage and air
      adjacent to an activated sludge plant. Both showed temporal variation but the
      mean count of phages in enterovirus-positive samples was not significantly
      different from that in enterovirus-negative samples. Hence coliphages are not
      necessarily a good indicator of enteroviruses in sewage and aerosols.

PMID- 7576511
TI  - Antibacterial activity of flavanostilbenes against methicillin-resistant
      Staphylococcus aureus.
AB  - Three phytochemical compounds (alopecurone A-C), flavanostilbenes which are
      produced by condensation between a hydroxyflavanone and a hydroxystilbene, were
      isolated as major components from the root of Sophora alopecuroides. They
      uniformly inhibited the growth of 21 strains of methicillin-resistant
      Staphylococcus aureus with minimum inhibitory concentrations of 3.13-6.25
      micrograms ml-1.

PMID- 7576512
TI  - Sulphate-reducing bacteria in bovine faeces.
AB  - Sulphate-reducing bacteria (SRB) were found in all of 200 bovine faeces examined.
      The number of SRB in bovine faeces ranged from 5 x 10(2) to 6 x 10(8) bacteria g
      1. Of 50 isolates identified, all were assigned to the genus Desulfovibrio.

PMID- 7576513
TI  - The importance of methanogens associated with ciliate protozoa in ruminal methane
      production in vitro.
AB  - The importance of methanogenic bacteria associated with ciliate protozoa was
      estimated either by removing protozoa from whole rumen fluid (using defaunated
      rumen fluid to correct for the effects of centrifugation on bacteria) or by
      isolating the protozoa. Rumen fluid was withdrawn from sheep inoculated with
      either Polyplastron multivesiculatum, a co-culture of Isotricha prostoma plus
      Entodinium spp. or a mixed type B fauna of Entodinium, Eudiplodinium and
      Epidinium spp. Methanogenesis was highest in rumen fluid containing a mixed
      protozoal population of the following genera: Entodinium, Eudiplodinium and
      Epidinium, was lower in defaunated rumen fluid and lowest in rumen fluid
      containing either I. prostoma plus Entodinium or P. multivesiculatum.
      Methanogenic bacteria associated with rumen ciliates were apparently responsible
      for between 9 and 25% of methanogenesis in rumen fluid.

PMID- 7576515
TI  - Isolation and characterization of four polycyclic aromatic hydrocarbon degrading
      bacteria from soil near an oil refinery.
AB  - Four bacterial strains (I-IV) capable of optimum growth on 0.1% naphthalene,
      anthracene or a mixture of naphthalene and phenanthrene were isolated from soil
      near an oil refinery. Two isolates (I and II) were identified as belonging to the
      genus Micrococcus, while strains III and IV were identified as Pseudomonas and
      Alcaligenes respectively. All the isolates were found to bear high molecular
      weight plasmid DNA (isolate I and IV 89%, II 67.5% and III 92.1% of lambda DNA),
      which is presumed to aid in the metabolism of polycyclic aromatic hydrocarbons.
      The strains also showed appreciable growth at high concentrations of NaCl (up to
      7.5%).

PMID- 7576514
TI  - Antimicrobial effects of tea-tree oil and its major components on Staphylococcus
      aureus, Staph. epidermidis and Propionibacterium acnes.
AB  - Major components of two tea-tree oil samples were identified using thin layer and
      gas-liquid chromatography (TLC and GLC). Using a TLC-bioautographic technique,
      the tea-tree oils, terpinen-4-ol, alpha-terpineol and alpha-pinene were found to
      be active against Staphylococcus aureus, Staph. epidermidis and Propionibacterium
      acnes whereas cineole was inactive against these organisms. The MIC values of the
      three active compounds increased in the order alpha-terpineol < terpinen-4-ol <
      alpha-pinene for all three micro-organisms. MIC values of the tea-tree oils and
      terpinen-4-ol were lower for P. acnes than for the two staphylococci. This study
      supports the use of tea-tree oil in the treatment of acne, and demonstrates that
      terpinen-4-ol is not the sole active constituent of the oil.

PMID- 7576516
TI  - A comparison of immunomagnetic separation plus enrichment with conventional
      Salmonella culture in the examination of raw sausages.
AB  - Immunomagnetic separation with additional enrichment was used in conjunction with
      improved selective media to improve the isolation of salmonellae from raw
      sausages. The isolation rate achieved was almost double that of conventional
      culture with no increase in processing time. The selective media gave an overall
      specificity of approximately 74%; all false-positive pickoffs being identified as
      Citrobacter freundii. It is believed that this method represents a significant
      advance in the isolation of salmonellae from foods, although the ideal media both
      for enrichment and selection have yet to be found.

PMID- 7576517
TI  - Development of a selective plating technique for the recovery of Escherichia coli
      O157:H7 after heat stress.
AB  - The use of Sorbitol MacConkey Agar supplemented with 4-methylumbelliferyl beta-D
      glucuronide (MSMA), which is commonly used in the isolation of Escherichia coli
      O157:H7, has been shown to perform poorly when stressed cells of the pathogen are
      present. The incorporation of a resuscitation period (2 h at 25 degrees C) on
      Trypticase Soy Agar (TSA) before overlay with MSMA was found to significantly (P
      < or = 0.01) improve recovery of heat-stressed (52 degrees C/60 min) cells.
      Maximal recovery was, however, obtained by adding catalase (1000 U) to the TSA
      before overlaying with MSMA. This recovery protocol was shown not to result in
      the loss of the major known virulence factors of E. coli O157:H7 (genes encoding
      eae, VT1 and VT2).

PMID- 7576518
TI  - Effect of freezing of water samples on viable counts of environmental
      mycobacteria.
AB  - The effect of prolonged storage on mycobacteria and other heterotrophic bacteria
      in brook water samples was examined by determination of viable counts from fresh
      samples and again after water concentrates had been stored in nutrient broth at 
      75 degrees C for 15 months. The counts of mycobacteria were on average three
      times higher after storage (range of ratio 0.9-10.4). In contrast, the viable
      counts of other heterotrophic bacteria were reduced by 69%. The increase in
      mycobacterial counts was probably due to break-up of microcolonies or release of
      attached bacteria from particles. The possibility of cultivating mycobacteria
      from frozen samples is of practical help in large-scale field surveys.

PMID- 7576519
TI  - An improved Escherichia coli-Rhodococcus shuttle vector and plasmid
      transformation in Rhodococcus spp. using electroporation.
AB  - The genetic studies of metabolically diverse Rhodococcus spp. have been hampered
      by the lack of a system of introducing exogenous DNA. The authors improved an
      existing Escherichia coli-Rhodococcus shuttle vector (pMVS301) by removing much
      of the DNA not needed for replication and adding a multicloning site. This
      improved vector (pBS305) is 7.9 kb in length. Its ability to transform
      Rhodococcus was tested using electroporation parameters optimized for
      introduction of pMVS301 into Rhodococcus. Transformation efficiencies as high as
      10(5) cfu micrograms-1 DNA were obtained although efficiencies varied depending
      on the Rhodococcus strain tested. The improved vector pBS305 offers great utility
      for genetic studies of Rhodococcus because its small size enables movement of
      large inserts of DNA into Rhodococcus, it has multicloning sites, contains a
      highly selective thiostrepton marker, and can be replicated in both E. coli and
      Rhodococcus.

PMID- 7576520
TI  - Preliminary study of microbiological parameters in eight inland recreational
      waters. Public Health Laboratory Service Water Surveillance Group.
AB  - A pilot survey of the counts of total coliform bacteria, thermotolerant coliform
      bacteria, Escherichia coli and faecal streptococci was carried out at eight
      inland recreational waters at weekly intervals during July 1991. The aims were to
      assess the feasibility of determining candidate indicators of recreational water
      quality and to assess the possible scale of variability of these parameters. The
      numbers of total coliforms were difficult to determine reliably because of
      interference from the background bacterial flora. There was a strong correlation
      between thermotolerant coliforms and E. coli and faecal streptococci. The average
      counts of the indicator organisms varied between and within the eight
      recreational waters by up to 10,000-fold. The greatest variation was between the
      eight recreational waters. At any one water, the greatest source of variation was
      time but there was substantial variation between sample points at one time.
      Counts in samples collected 1 m apart exhibited greater than random variation.
      Counts from surface samples tended to be higher than those at 30 cm or 100 cm
      depth. The proportion of thermotolerant coliforms confirmed to be E. coli varied
      from water to water between 60% and 96%.

PMID- 7576522
TI  - Effect of polyols on heat inactivation of Aspergillus niger van Teighem
      inulinase.
AB  - The effect of polyols (ethylene glycol, glycerol, erythritol, xylitol and
      sorbitol) on partially purified inulinase from Aspergillus niger van Teighem
      mutant grown on Kuth (Saussurea lappa) root as source of inulin was determined.
      Seventy per cent of inulinase activity was retained in the presence of 4 mol l-1
      sorbitol at 75 degrees C.

PMID- 7576521
TI  - Fermentation of glucose and xylose in ruminal strains of Butyrivibrio
      fibrisolvens.
AB  - Metabolism of glucose and xylose and parameters of growth were investigated in
      strains of Butyrivibrio fibrisolvens ATCC 19171 and CE 51. In the strain ATCC
      19171, the composition of fermentation end-products was the same in cultures
      supplied with glucose and xylose. The strain CE 51 produced more volatile fatty
      acids and less lactate from xylose than from glucose. Cells of this strain grown
      on xylose possessed phosphoketolase activity (EC 4.1.2.9). In both strains the
      production of cell dry matter and growth rate were higher in cultures supplied
      with glucose. In xylose-grown cultures butyrivibrios tended to convert more
      substrate carbon into metabolites and less into cellular material than in
      cultures grown on glucose.

PMID- 7576523
TI  - A gene-targeting suicide vector for Streptococcus bovis.
AB  - A gene-targeting suicide vector for Streptococcus bovis has been constructed
      using the Escherichia coli/Streptococcus shuttle plasmid, pMU1328, and a region
      derived from the broad host-range, Gram-positive transposon, Tn916. This suicide
      plasmid replicates autonomously in E. coli, but not in Strep. bovis or Strep.
      bovis Tn916. Under positive selection, the plasmid was shown to integrate into
      Strep. bovis Tn916 chromosomal DNA at a frequency of 3 x 10(-8) cell-1 and was
      stably maintained for at least 100 generations in the absence of selection. This
      is the first report of a recombination system in ruminal bacteria. The ability to
      target genes, knock out specific functions or introduce novel genes into these
      micro-organisms will allow ruminal species to be manipulated and may eventually
      lead to improved animal production.

PMID- 7576524
TI  - Effect of water activity and temperature on growth and fumonisin B1 and B2
      production by Fusarium proliferatum and F. moniliforme on maize grain.
AB  - The effect of different water activities (aw, 0.968, 0.956, 0.944, 0.925) and
      temperature (25 degrees C and 30 degrees C) on colonization and production of
      fumonisin B1 (FB1) and B2 (FB2) on sterile layers of maize by Fusarium
      proliferatum and F. moniliforme isolates was determined over periods of 6 weeks.
      Generally, both F. moniliforme and F. proliferatum grew faster with increasing aw
      and best at 30 degrees C. All three isolates produced more FB1 than FB2
      regardless of aw or temperature. Very little FB1 and FB2 were produced at 0.925
      aw, with maximum produced at 0.956 and 0.968 aw at both temperatures tested. Most
      FB1 and FB2 were produced by F. moniliforme (25N), followed by F. proliferatum
      isolates (73N and 131N). At all aw levels and both temperatures there was an
      increase in FB1 and FB2 concentration with time. Statistical analyses of aw,
      temperature, time, two- and three-way interactions showed some significant
      differences between isolates and FB1 and FB2 production.

PMID- 7576525
TI  - Recovery of heat-injured spores of Clostridium perfringens types B, C and D by
      lysozyme and an initiation protein.
AB  - Heat-injured spores of several strains of Clostridium perfringens types B, C and
      D could be partially recovered if lysozyme was included in the recovery medium.
      As little as 25 ng ml-1 was effective. D90 degrees C values of 1.3-2.6 were
      obtained with an approximate 2-3-fold increase in the presence of 1 /microgram ml
      1 of lysozyme. In the absence of lysozyme, prolonged heating of spores resulted
      in the appearance of satellite colonies surrounding colonies of surviving spores.
      An initiation protein, previously reported in the case of type A strains, was
      also produced by type B, C and D strains. When added to the recovery medium it
      too promoted the recovery of spores from thermal injury though not as effectively
      as lysozyme.

PMID- 7576527
TI  - Bacillus thuringiensis serovar higo (flagellar serotype 44), a new serogroup with
      a larvicidal activity preferential for the anopheline mosquito.
AB  - Eight strains of Bacillus thuringiensis, isolated in Japan, formed spherical
      parasporal inclusions and exhibited low to moderate larvicidal activities for two
      mosquito species, Anopheles stephensi and Culex pipiens molestus, but not for
      another dipteran, Telmatoscopus albipunctatus, or two lepidopterans, Bombyx mori
      and Hyphantria cunea. The anopheline toxicity (LC50 = 6.3 micrograms ml-1) was >
      10 times greater than the activity on the Culex mosquito. These strains were
      assigned to a previously undescribed flagellar (H) antigenic group. On the basis
      of the representative strain, 92-KU-137-4, a serogroup with H antigen 44,
      Bacillus thuringiensis serovar higo was established as new.

PMID- 7576526
TI  - Aerobic degradation and dechlorination of 2-chlorophenol, 3-chlorophenol and 4
      chlorophenol by a Pseudomonas pickettii strain.
AB  - A Gram-negative aerobic bacterium capable of using 2-chlorophenol (2-CP), 3
      chlorophenol (3-CP) and 4-chlorophenol (4-CP) as sole carbon sources was isolated
      and characterized. The bacterium, designated LD1, was identified to be a
      Pseudomonas pickettii strain. LD1 was able to totally degrade and dechlorinate 2
      CP (initial concentration: 1.51 mmol l-1), 3-CP (initial concentration: 0.57 mmol
      l-1) and 4-CP (initial concentration: 0.75 mmol l-1) within 30, 30 and 40 h of
      incubation, respectively, under growing-cell batch conditions. LD1 was also found
      to be able to metabolize chlorocatechols in growing- and resting-cell conditions.
      This suggests that the bacterium degrades monochlorophenols through a
      chlorocatechol pathway. In addition, LD1 was found to be capable of readily
      metabolizing other organic compounds such as phenol, benzoic acid, hydroxybenzoic
      acids and hydroquinone. Because of the broad spectrum of monochlorophenols and
      organic compounds that LD1 can degrade, this bacterium appears to have the
      potential for being successfully used in the biotreatment of wastewaters and in
      soil decontamination.

PMID- 7576528
TI  - Lecithinase reaction of Staphylococcus aureus strains of different origin on
      Baird-Parker medium.
AB  - Staphylococcus aureus produces one or more enzymes with lipolytic activity, but
      differences between strains have been reported (Owens and John 1975; O'Toole
      1987; Rollof et al. 1987). The biological and biochemical properties of these
      enzymes have been investigated and results were recently reviewed (Kotting et al.
      1984). Baird-Parker medium (Baird-Parker 1962) is a selective medium commonly
      used for the isolation of Staph. aureus. The presence of egg yolk in this medium
      permits the detection of two reactions due to lipolytic activity of
      staphylococci: (1) Lecithinase reaction, a zone of precipitate in the medium
      surrounding the colonies; and (2) Lipase reaction or 'pearly layer', an
      iridescent film in and immediately surrounding colonies, visible by reflected
      light (iridescent sheen or 'oil in water'). In this study, human and bovine
      strains, previously biotyped according to the scheme of Devriese et al. (1984),
      were compared for production of a zone of precipitation, lecithinase reaction, on
      Baird-Parker medium. Bovine and human strains of Staph. aureus were compared for
      production of the egg yolk reaction (lecithinase reaction) on Baird-Parker medium
      and the results were related to their biotypes and site of origin of the sample.
      Human strains and strains biotyped as human biotypes had higher percentage of
      positive results than bovine isolates and/or biotypes. However, all strains
      isolated from body sites of heifers produced a positive reaction regardless of
      the biotype.

PMID- 7576529
TI  - Isolation of uracil auxotrophs from Burkholderia cepacia ATCC 25416.
AB  - Two uracil auxotrophs of the phytopathogen Burkolderia cepacia ATCC 25416, which
      is known to be involved in food spoilage, were isolated by a combination of
      ethylmethane sulphonate and D-cycloserine counterselection. One mutant exhibited
      depressed orotate phosphoribosyltransferase activity while the other mutant
      lacked orotidine 5'-monophosphate decarboxylase activity. Pyrimidine limitation
      of either auxotroph elevated aspartate transcarbamoylase and dihydroorotase
      activities by at least 1:5-fold indicating that these pathway enzymes may be
      repressible by a uracil-related compound in B. cepacia. Overall, regulation of de
      novo pyrimidine synthesis in the uracil auxotrophs of B. cepacia ATCC 25416 was
      observed.

PMID- 7576530
TI  - Pyrimidine synthesis in Burkholderia cepacia ATCC 25416.
AB  - Pyrimidine synthesis in the food spoilage agent Burkholderia cepacia ATCC 25416
      was investigated. The five de novo pathway enzymes of pyrimidine biosynthesis
      were found to be active in B. cepacia ATCC 25416 and growth of this strain on
      uracil had an effect on the de novo enzyme activities. The in vitro regulation of
      aspartate transcarbamoylase activity in B. cepacia ATCC 25416 was studies and its
      activity was inhibited by PP(i), ATP, GTP, CTP and UTP. The enzymes cytidine
      deaminase, uridine phosphorylase and cytosine deaminase were found to be active
      in the salvage of pyrimidines in ATCC 25416. Overall, de novo pyrimidine
      synthesis in B. cepacia ATCC 25416 was regulated at the level of enzyme activity
      and its pyrimidine salvage enzymes differed from those found in B. cepacia ATCC
      17759.

PMID- 7576531
TI  - Purification and partial characterization of a novel thermophilic
      carboxylesterase with high mesophilic specific activity.
AB  - An esterase activity obtained from a strain of Bacillus stearothermophilus was
      purified 5,133-fold to electrophoretic homogeneity with 26% recovery. The
      purified esterase had a specific activity of 2,032 mumol min-1 mg-1 based on the
      hydrolysis of p-nitrophenyl caproate at pH 7.0 and 30 degrees C. The apparent
      molecular mass was 50,000 +/- 2,000 daltons from sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and 45,000 +/- 3,000 daltons from gel
      filtration. Native polyacrylamide gels stained for esterase activity showed three
      bands. The isoelectric points were estimated to be 5.7, 5.8, and 6.0. Forty amino
      acid residues were sequenced at the N-terminus. The sequence showed no
      degeneracy, suggesting that the three esterases are functionally identical
      carboxylesterases differing by a limited number of amino acids. The enzyme showed
      maximum activity at pH 7.0 and was very stable at pH 6.0-8.9 with optimum
      stability at pH 6.0. At this pH and 60 degrees C the half-life was 170 h.
      Esterase activity was totally inhibited by phenylmethanesulfonyl fluoride,
      parahydroxymercuribenzoate, eserine, and tosyl-L-phenylalanine, but not by
      ethylendiaminetetra acetic acid. The esterase obeyed Michaelis-Menten kinetics in
      the hydrolysis of p-nitrophenyl esters, but both Vmax and KM were protein
      concentration-dependent. The esterase was able to hydrolyse a number of p
      nitrophenyl derivatives (amino acid derivatives and aliphatic acids with
      different chain lengths).

PMID- 7576532
TI  - Characterization of changes in the glycosylation pattern of recombinant proteins
      from BHK-21 cells due to different culture conditions.
AB  - The N-glycosylation patterns of a genetically engineered human interleukin-2
      variant glycoprotein (IL-Mu6), produced by BHK-21 cells from long-term suspension
      and microcarrier cultures in the presence and absence of fetal calf serum were
      compared. IL-Mu6 was used as a model protein in studying the effect of different
      controlled cell culture conditions on the expression of N-glycans in recombinant
      glycoproteins. IL-Mu6 contains a single amino acid substitution (Glu100<==>Asn)
      generating a potential N-glycosylation recognition site (Asn100-Xxx-Thr/Ser) in
      addition to the natural O-glycosylation at position Thr3. Parallel cell
      cultivations were carried out in two continuously perfused 2.5-liter stirred
      bioreactors under defined culture conditions. Major differences were found in the
      glycoprotein products obtained during these different cultivation conditions.
      Serum-free cultures resulted in a higher level of terminal sialylation and
      proximal alpha 1-6 fucosylation. The ratio of O- to N-glycans as well as the
      amount of nonglycosylated product and the antennarity of N-linked carbohydrates
      in the model protein exhibited major differences depending on the presence or
      absence of serum, the condition of growth and the cultivation procedure.

PMID- 7576533
TI  - Production in Escherichia coli of a functional murine and murine::human chimeric
      F(ab')2 fragment and mature antibody directed against human placental alkaline
      phosphatase.
AB  - We report the production in Escherichia coli of a murine antibody IgG2b, a
      murine::human chimeric antibody IgG3 and the corresponding F(ab')2 fragments, all
      directed against human placental alkaline phosphatase, a tumor marker. The cDNA
      of the heavy chain of the mature antibodies and their fragments were linked up to
      the bacterial alkaline phosphatase signal sequence and were placed under control
      of the inducible tac promoter. Coexpression with the murine kappa light chain
      resulted in production of functional dimeric, trimeric and tetrameric, mature
      antibodies and F(ab')2 fragments in the periplasm of E. coli in a yield of 200
      300 micrograms l-1. High amounts of light and heavy chains were present also in
      the insoluble fraction.

PMID- 7576534
TI  - Flux analysis of microbial metabolic pathways using a visual programming
      environment.
AB  - This paper describes the use of a visual programming environment (LabVIEW) for
      the flux analysis of metabolic pathways. Representations of metabolic pathways
      are constructed in software from individual reaction elements (icons) which are
      linked together to indicate potential flux routes. Off-line bioprocess data are
      then used to supply the inputs and outputs to the metabolic pathway and the
      pathway fluxes are calculated. The metabolic system can be modelled at different
      levels of complexity and new pathways can be inserted into existing models. To
      illustrate this, flux analyses are performed on three Escherichia coli mutants
      with metabolic pathway deletions and insertions. The first analysis looks at
      organic acid production and the second at the effect of the presence in E. coli
      of an engineered pathway for toluene degradation.

PMID- 7576536
TI  - Optimising the recovery of recombinant thermostable proteins expressed in
      mesophilic hosts.
AB  - The purification of a thermostable Caldocellum saccharolyticum beta-glucosidase
      expressed in Escherichia coli was investigated using heat precipitation of
      unclarified cell homogenates. Heat treatment at 70 degrees C was capable of
      purification with respect to cell debris, small particulates and the majority of
      cell protein, although E. coli proteins were even more efficiently removed at 80
      degrees C and above. For thermostable proteins expressed in E. coli, a
      precipitation temperature of 80 degrees C or greater is recommended for optimal
      removal of contaminant proteins. In small-scale heating trials, heating rate was
      found to influence enzyme yield significantly. Losses were minimised when 'flash
      heating' was employed. The successful single-step removal of particulates, labile
      protein and nucleic acids was achieved by simultaneous heat-treatment and
      polyethyleneimine addition, although the purification achieved was additive
      rather than synergistic.

PMID- 7576535
TI  - Specific growth rate as a parameter for tracing growth-limiting substances in
      animal cell cultures.
AB  - The specific growth rate (mu) reaches its maximum very early during culture (at
      20 h), but declines again thereafter so that no exponential growth phase occurs
      in batch cultures of hybridoma cells. This growth rate limitation depends neither
      on exhaustion of any of the macro-nutrients, nor on inhibition by metabolic
      byproducts (Ljunggren and Haggstrom, 1994). Intermittent additions of serum,
      after 20 and 40 h of culture, resulted in exponential growth throughout the
      growth phase. Insulin was found to be the main component responsible for the
      growth rate increasing effect. Intermittent additions of serum or insulin to a
      dual substrate (glucose and glutamine) limited fed batch culture increased the
      growth rate also here, and the results indicate the existence of a minimum growth
      rate (about 0.02 h-1) at a threshold glutamine level (0.005 mM). Serum and
      insulin additions markedly enhanced the glucose consumption and lactate formation
      rates, a metabolic effect that was not coupled to the increase in mu. The reduced
      concentrations of glucose and glutamine in substrate limited fed batch cultures
      suppressed substrate consumption rates and byproduct formation (lactate,
      ammonium, alanine, other amino acids) even in the serum and insulin stimulated
      cultures and rendered the energy metabolism much more efficient than in batch
      culture. Further, the serum and insulin stimulated cells growing in substrate
      limited fed batch culture produced almost 4-times more antibodies, from the same
      amount of nutrients as supplied to the batch grown cells.

PMID- 7576537
TI  - Continuous cultivation of Penicillium chrysogenum. Growth on glucose and
      penicillin production.
AB  - A series of constant-mass, continuous cultivations of the penicillin producing
      mold Penicillium chrysogenum was carried out using a chemically defined medium
      with glucose as the growth-limiting component. The stoichiometry for growth of P.
      chrysogenum on glucose was characterized in terms of mass-yield and maintenance
      coefficients. Saturation kinetics with respect to glucose was used to describe
      the glucose consumption rate at steady-state conditions. Transient data indicate
      that the maximum rate of glucose consumption at a particular set of operating
      conditions is correlated to the metabolic 'capacity' of the mold as reflected by
      its intracellular RNA content. A progressive loss in the penicillin productivity
      in glucose limited chemostat cultures was correlated to the formation of two
      mutants. The two mutants were characterized by their sporulation when grown as
      surface cultures and by Southern dot-tests for delta-(L-alpha-aminoadipyl)-L
      cysteinyl-D-valine synthetase (ACVS), isopenicillin-N synthase (IPNS) and acyl
      CoA:6-APA acyltransferase (AT). The loss of penicillin productivity was caused by
      an increasing fraction of mutants which had lost the genes encoding for all three
      enzymes needed in the penicillin synthesizing pathway.

PMID- 7576539
TI  - An acetylglucomannan esterase of Aspergillus oryzae; purification,
      characterization and role in the hydrolysis of O-acetyl-galactoglucomannan.
AB  - An acetyl glucomannan esterase (AGME) was purified to electrophoretic homogeneity
      from the culture supernatant of Aspergillus oryzae. This new enzyme had a
      molecular mass of 36 kDa and an isoelectric point of 4.6. It was most active in
      the pH range 5.0-5.5 and was stable for 24 h at 40 degrees C at pH 5.0-6.0. The
      purified esterase liberated acetic acid from O-acetyl-galactoglucomannan, O
      acetyl-4-O- methylglucuronoxylan and alpha-naphtyl acetate. The specific activity
      was 10-times higher for acetylated mannan than for acetylated xylan. The enzyme
      was able to act on polymeric substrate but activity was clearly enhanced by
      addition of mannanase from Trichoderma reesei and alpha-galactosidase from guar
      seeds. Presence of mannanase also increased the liberation of acetic acid in long
      term hydrolysis (24 h), while the addition of alpha-galactosidase had no effect.
      No significant synergism between these two glycanases and the previously
      characterized esterase of A. oryzae (FE), which is also able to deacetylate
      galactoglucomannan, was observed. Even though the AGME had 8-times higher
      specific galactomannan deacetylating activity than the FE, the maximum amount of
      acetic acid liberated from the polymeric galactoglucomannan by AGME was only 80%
      of that of FE. Both esterases clearly enhanced the action of mannanase and alpha
      galactosidase in the degradation of O-acetyl-galactoglucomannan isolated from
      Norway spruce.

PMID- 7576540
TI  - Hydrophobicity engineering to facilitate surface display of heterologous gene
      products on Staphylococcus xylosus.
AB  - Protein engineering has been employed to investigate the effect of specific amino
      acid changes on the targeting of heterologous proteins to the outer cell surface
      of the Gram-positive bacterium Staphylococcus xylosus. Three different variants,
      corresponding to a 101 amino acid region of the major glycoprotein (G protein) of
      human respiratory syncytial virus (RSV), were generated in which multiple
      hydrophobic phenylalanine residues were either substituted or deleted. The
      different G protein fragments were expressed as one part of recombinant receptors
      designed for surface display on S. xylosus cells. The engineered variants of the
      RSV G protein hybrid receptors were, in contrast to a non-engineered fragment,
      efficiently targeted to the outer cell surface of recombinant S. xylosus cells as
      determined by different methods, including fluorescence-activated cell sorting.
      In addition, immunization of mice with live recombinant S. xylosus demonstrated
      that surface exposure was required to generate receptor-specific antibodies. The
      present strategy of hydrophobic engineering should be of general interest in
      surface-display applications and for secretion of proteins otherwise difficult to
      translocate through host cell membranes.

PMID- 7576538
TI  - Purification and characterization of alpha 1-antitrypsin secreted by recombinant
      yeast Saccharomyces diastaticus.
AB  - The secreted human alpha 1-antitrypsin (alpha 1AT) produced by yeast was purified
      from the culture medium by ultrafiltration, ammonium sulfate fractionation (60
      75% saturation), protamine sulfate treatment, and ion-exchange chromatography.
      Molecular mass of the purified alpha 1AT was 52 kDa, which is similar to that of
      human plasma alpha 1AT. Yeast-produced alpha 1AT was fully functional as an
      inhibitor compared with the plasma form. Unlike plasma alpha 1AT, however,
      treatment of the yeast-produced alpha 1AT with endoglycosidase H decreased the
      molecular mass to that of recombinant alpha 1AT produced in Escherichia coli,
      indicating the high-mannose type N-linked glycosylation of the secreted alpha
      1AT. Glycosylation in yeast cells enhanced kinetic stability of alpha 1AT towards
      heat deactivation.

PMID- 7576542
TI  - Pilot-scale harvest of recombinant yeast employing microfiltration: a case study.
AB  - In order to develop a cost-effective recovery process for an intracellular
      product, crossflow microfiltration was studied for the harvest of a recombinant
      yeast under severe time constraint. It was required to process yeast broth in a
      short period of time to minimize the risk for product degradation. Preliminary
      microfiltration studies employing flat sheet membranes showed high throughout
      with initial fluxes on the order of water fluxes (> 1000 LMH, regime I, < 2 min),
      followed by a rapid decay towards a low pseudo-steady state flux (20 LMH, regime
      II, > 2 min). Exploitation of these high fluxes and control of their eventual
      decline were crucial in establishing a rapid crossflow filtration process. The
      effect of several parameters, such as initial cell concentration, shear rate,
      transmembrane pressure, membrane pore size and medium composition on filtration
      performance were investigated to better understand the flux decline mechanisms.
      We found that the major contributor to flux decay was reversible fouling by the
      cake formation on the membrane surface. Within the operating boundaries of our
      microfiltration system, large-pore membrane (0.65 micron) was much more desirable
      for harvesting our yeast (10 microns size) without cell leakage than smaller pore
      ones (0.22 micron and 0.45 micron). Among adjustable operating parameters, feed
      flow rate (i.e., shear rate) exerted significant impact on average flux, whereas
      manipulation of transmembrane pressure afforded little improvement. Although
      initial cell concentration affected adversely the permeation rates, growth medium
      components, especially soy-peptone, was deemed pivotal in determining the
      characteristics of cell cake, thus controlling yeast microfiltration.

PMID- 7576541
TI  - Production of the chimerical plasminogen activator K2tu-PA in CHO cells.
AB  - Development of a CHO cell-based production system for the hybrid plasminogen
      activator K2tu-PA is described. Using the major immediate-early promoter of mouse
      cytomegalovirus (MCMV) transient and stable expression levels were 3-10-fold
      higher than those obtained with several other strong promoters. Splicing and
      polyadenylation signals from the rabbit beta-globin gene were used downstream of
      the DNA segment coding for K2tu-PA. The strong enhancer moiety of the MCMV
      promoter also stimulated strongly the promoter of the dihydrofolate reductase
      (DHFR) gene, placed adjacently for selection/gene amplification purposes. One
      construct with opposing K2tu-PA and DHFR RNA transcripts yielded the highest
      expression level with a single copy of the plasmid, but K2tu-PA expression was
      consistently lost after amplification of such genes, possibly as a result of the
      formation of antisense RNA. With other constructs, K2tu-PA production leveled off
      at 6.5 micrograms per million cells per day despite a high gene copy number. This
      was due to a combination of inefficient mRNA translation and mRNA instability,
      caused by elements from the untranslated portions of tissue-type and urokinase
      type plasminogen activator cDNA which were included in the expression vector.
      After elimination of these inhibitory DNA segments, 4-5-times higher expression
      levels were reached.

PMID- 7576543
TI  - Population balance models of autonomous microbial oscillations.
AB  - Autonomous oscillations in continuous microbial cultures is well documented for
      the case of baker's yeast, Saccharomyces cerevisiae, for which it has been
      observed under a range of operating conditions. We have found that autonomous
      microbial oscillations can be modeled by unstructured population balance models
      in which a key cell cycle parameter is a function of the environmental
      conditions, e.g., the concentration of a substrate or product. Although these
      models are remarkably simple, they can display a wide range of dynamic behaviors.
      These behaviors include, for binary fission organisms, solutions containing a
      single synchronous population and, for budding yeasts, two synchronized
      subpopulations with a period of oscillation similar to that of the cell cycle
      length, a pattern that has been observed experimentally in S. cerevisiae.
      Numerical simulations of the model equations also show that complex periodic
      solutions with periods very different from the cell cycle length are possible.
      The ability of the population balance approach to accurately describe the
      available data of yeast culture dynamics will be discussed.

PMID- 7576544
TI  - Solution and properties of age population balance models which assume discrete
      division ages.
AB  - A solution procedure for models of the transient age distribution which employ
      the assumption of discrete, constant division ages is developed. The solutions
      for the final state of the age distribution, the solutions obtained in the limit
      as time goes to infinity, are found to have properties which do not make
      biological sense. In particular, the solutions will only approach the steady
      state solution for very special initial conditions. For most initial conditions,
      the solution for the final state will instead exhibit an oscillatory behavior. In
      addition, the oscillatory solutions are unstable with respect to changes in
      values of the model parameters and solutions with very different periods of
      oscillation are found arbitrarily close to each other in the parameter space.
      Models which assume discrete division ages must therefore be used with caution
      and may be unsuitable as models of autonomous microbial oscillations.

PMID- 7576545
TI  - Performance of a membrane-dialysis bioreactor with a radial-flow fixed bed for
      the cultivation of a hybridoma cell line.
AB  - A bioreactor system for the continuous cultivation of animal cells with a high
      potential for scale-up is presented. This reactor system consists of radial-flow
      fixed-bed units coupled with a dialysis module The dialysis membrane enables the
      supply of low-molecular-weight nutrients and removal of toxic metabolites, while
      high-molecular-weight nutrients and products (e.g., monoclonal antibodies) are
      retained and accumulated. This concept was investigated on the laboratory scale
      in a bioreactor with an integrated dialysis membrane. The efficiency of the
      reactor system and the reproducibility of the cell activity (hybridoma cells)
      under certain process conditions could be demonstrated in fermentations up to 77
      days. Based on model calculations, an optimized fermentation strategy was
      formulated and experimentally confirmed. Compared to chemostat cultures with
      suspended cells, a ten-times higher mAb concentration (383 mg1(-1)) could be
      obtained. The highest volumetric specific mAb production rate determined was 6.1
      mg mAb (1 fixed bed)-1h-1.

PMID- 7576546
TI  - Liquid-culture pH, temperature, and carbon (not nitrogen) source regulate
      phenazine productivity of the take-all biocontrol agent Pseudomonas fluorescens 2
      79.
AB  - Strain 2-79 is a biocontrol agent against take-all, an important disease of wheat
      caused by Gaeumannomyces graminis var. tritici. In the rhizosphere, it produces
      the antibiotic phenazine 1-carboxylic acid (PCA) as the primary means of disease
      suppression. One barrier to commercial use of phenazine-producing pseudomonads,
      like strain 2-79, is the lack of liquid-culture technology for mass production.
      For instance, there is little published research concerning the impact of liquid
      culture secondary metabolism on the biocontrol qualities of the cell harvest,
      i.e., efficacy, phytotoxicity, and storage survival. Yet it is important to know
      whether the fermentation process should be designed to enhance or eliminate
      secondary metabolite accumulation. To enable future exploration of this issue, we
      identified liquid-culture parameters that could be manipulated to control the
      phenazine productivity of strain 2-79. Our results indicated that PCA
      accumulation was very sensitive to the culture pH and temperature. It was
      possible to produce large cell populations with either high or low phenazine
      productivity by choosing to control culture pH at 7 and 8 respectively. Although
      high cell accumulations were achieved over the broad 25-34 degrees C range
      studied, high, moderate, or low PCA productivities were observed at 25-27 degrees
      C, 29-32.5 degrees C, or 34 degrees C respectively. When pH was controlled at 7,
      specific PCA productions at 25 degrees C could be modulated by the choice of
      carbon source supplied. PCA accumulation per unit biomass reached 0.31 g/g on
      glucose, 0.16 g/g on glycerol and xylose, and only 0.09 g/g on fructose.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576547
TI  - Production and properties of three pectinolytic activities produced by
      Aspergillus niger in submerged and solid-state fermentation.
AB  - Three extracellular pectinases were produced by Aspergillus niger CH4 by
      submerged and solid-state fermentation, and their physicochemical and kinetic
      properties were studied. The highest productivities of endo- and exo-pectinase
      and pectin lyase were obtained with solid-state fermentation. The kinetic and
      physicochemical properties of these enzymes were influenced by the type of
      culture method used. All activities were very different in terms of pH and
      temperature optima, stability at different pH and temperature values and affinity
      for the substrate (Km values). In solid-state fermentation, all pectinase
      activities were more stable at extreme pH and temperature values but the Km
      values of endo-pectinase and pectin lyase were higher with respect to those
      activities obtained by the submerged-culture technique. The pectin lyase activity
      obtained by the submerged-culture technique showed substrate inhibition but the
      enzyme obtained by solid-state fermentation did not. Electrophoresis, using
      sodium dodecyl sulphate/polyacrylamide gel with enzymatic extracts obtained for
      both culture methods, showed the same number of protein bands but some
      differences were found in their electrophoretic position. The results obtained in
      this work suggest that the culture method (submerged or solid-state) may be
      responsible for inducing changes in some of the pectinolytic enzymes produced by
      A. niger.

PMID- 7576549
TI  - Optimal dynamic experiments for bioreactor model discrimination.
AB  - This paper describes a general approach for dynamic model discrimination for
      continuous cultures and presents dynamic models for pure cultures of E. coli and
      C. utilis obtained using the method. For each pure culture system, four candidate
      models representing various levels of structure were considered. All models
      reduce to Monod growth kinetics at steady state. An optimized set of
      multivariable step inputs in selected manipulative variables was used to
      discriminate between candidate models. The models that best predicted the dynamic
      behavior were selected by comparison of model predictions with experimental data.
      Two discrimination functions were compared in terms of their ability to determine
      the optimal set of multivariable step inputs to discriminate between candidate
      models. Results indicate that model discrimination based on maximizing the
      minimum absolute difference between any two models for a given set of inputs
      possessed good potential for discrimination between candidate models. Models
      selected for E. coli and C. utilis from the model discrimination work are
      presented and compared with experimental data.

PMID- 7576548
TI  - Fermentation of whey and starch by transformed Saccharomyces cerevisiae cells.
AB  - Among the main agro-industrial wastes, whey and starch are of prime importance.
      In previous work we showed that strains of Saccharomyces cerevisiae transformed
      with the episomal plasmid pM1 allow production of yeast biomass and ethanol from
      whey/lactose. Ethanol production from whey and derivatives has been improved in
      computer-controlled bioreactors, while fermentation studies showed that the
      composition of the medium greatly modulates the productivity (g ethanol
      produced/l in 1 h of fermentation). A yeast strain for the simultaneous
      utilization of lactose and starch has also been developed. Biotechnological
      perspectives are discussed.

PMID- 7576550
TI  - Stable multicopy integration of vector sequences in Hansenula polymorpha.
AB  - Plasmids without an origin of replication, but bearing the URA3 gene of
      Saccharomyces cerevisiae as a selective marker for transformation, are shown to
      replicate autonomously in Hansenula polymorpha, indicating that parts of the S.
      cerevisiae URA3 gene can fulfil an autonomous replication and stabilization
      function in H. polymorpha. Such plasmids, replicated in low copy number in
      monomeric conformation, could be rescued in E. coli, and showed a low mitotic
      stability under selective and non-selective conditions. Selective propagation of
      such transformants, however, led to the integration of plasmid sequences into the
      H. polymorpha genome. The integration event usually occurred in high copy number
      (approx. 30-50) at a single non-homologous site of the genome. The plasmid
      sequences were found to be present in tandem array and stable under non-selective
      conditions. In contrast, the use of homologous URA3 gene under similar conditions
      led to low-copy-number transformants.

PMID- 7576551
TI  - Characterization of recombinant E. coli ATCC 11303 (pLOI 297) in the conversion
      of cellulose and xylose to ethanol.
AB  - This work describes the characterization of recombinant Escherichia coli ATCC
      11303 (pLOI 297) in the production of ethanol from cellulose and xylose. We have
      examined the fermentation of glucose and xylose, both individually and in
      mixtures, and the selectivity of ethanol production under various conditions of
      operation. Xylose metabolism was strongly inhibited by the presence of glucose.
      Ethanol was a strong inhibitor of both glucose and xylose fermentations; the
      maximum ethanol levels achieved at 37 degrees C and 42 degrees C were about 50
      g/l and 25 g/l respectively. Simultaneous saccharification and fermentation of
      cellulose with recombinant E. coli and exogenous cellulose showed a high ethanol
      yield (84% of theoretical) in the hydrolysis regime of pH 5.0 and 37 degrees C.
      The selectivity of organic acid formation relative to that of ethanol increased
      at extreme levels of initial glucose concentration; production of succinic and
      acetic acids increased at low levels of glucose (< 1 g/l), and lactic acid
      production increased when initial glucose was higher than 100 g/l.

PMID- 7576552
TI  - Debranching of arabinoxylan: properties of the thermoactive recombinant alpha-L
      arabinofuranosidase from Clostridium stercorarium (ArfB).
AB  - The gene arfB encoding alpha-L-arabinofuranosidase B of the cellulolytic
      thermophile Clostridium stercorarium was expressed in Escherichia coli from a 2.2
      kb EcoRI DNA fragment. The recombinant gene product ArfB was purified by fast
      performance liquid chromatography. It has a tetrameric structure with a monomeric
      relative molecular mass of 5200. The optima for temperature and pH are 70 degrees
      C and 5.0 respectively. The enzyme appears to have no metal cofactor requirement
      and is sensitive to sulfhydryl reagents. It hydrolyzes aryl and alkyl alpha-L
      arabinofuranosides and cleaves arabinosyl side-chains from arabinoxylan (oat
      spelt xylan) and from xylooligosaccharides produced by recombinant endoxylanase
      XynA from the same organism. The identify of the N-terminal amino acid sequences
      indicates that ArfB corresponds to the major alpha-arabinosidase activity present
      in the culture supernatant of C. stercorarium.

PMID- 7576553
TI  - Cloning, sequence and expression of the gene coding for rhamnogalacturonase of
      Aspergillus aculeatus; a novel pectinolytic enzyme.
AB  - Rhamnogalacturonase was purified from culture filtrate of Aspergillus aculeatus
      after growth in medium with sugar-beet pulp as carbon source. Purified protein
      was used to raise antibodies in mice and with the antiserum obtained a gene
      coding for rhamnogalacturonase (rhgA) was isolated from a lambda cDNA expression
      library. The cloned rhgA gene has an open-reading frame of 1320 base pairs
      encoding a protein of 440 amino acids with a predicted molecular mass of 45 962
      Da. The protein contains a potential signal peptidase cleavage site behind Gly-18
      and three potential sites for N-glycosylation. Limited homology with A. niger
      polygalacturonase amino acid sequences is found. A genomic clone of rhgA was
      isolated from a recombinant phage lambda genomic library. Comparison of the
      genomic and cDNA sequences revealed that the coding region of the gene is
      interrupted by three introns. Furthermore, amino acid sequences of four different
      peptides, derived from purified A. aculeatus rhamnogalacturonase, were also found
      in the deduced amino acid sequence of rhgA. A. aculeatus strains overexpressing
      rhamnogalacturonase were obtained by cotransformation using either the A. niger
      pyrA gene or the A. aculeatus pyrA gene as selection marker. For expression of
      rhamnogalacturonase in A. awamori the A. awamori pyrA gene was used as selection
      marker. Degradation patterns of modified hairy regions, determined by HPLC, show
      the recombinant rhamnogalacturonase to be active, and the enzyme was found to
      have a positive effect in the apple hot-mash liquefaction process.

PMID- 7576554
TI  - Purification of recombinant alpha-amylase by immunoaffinity chromatography with
      anti-peptide antibody.
AB  - Adsorption characteristics of an anti-peptide antibody, obtained by immunization
      of eight amino acids in the C-terminal region of chimeric alpha-amylase of rice
      alpha-amylase isozymes, were studied by use of the chimeric enzyme and the
      peptide used for immunization. This anti-peptide antibody adsorbed the enzyme, as
      well as the peptide antigen, with sufficient affinity for immunoaffinity
      purification and was used for purification of the enzyme secreted from yeast
      cells. Chimeric alpha-amylase was purified by immunoaffinity chromatography to
      high purity in one step from the fermentation broth. One-third of the secreted
      enzyme was not adsorbed by the column of anti-peptide antibody because of
      processing in the C-terminal region.

PMID- 7576555
TI  - CEN14 sequences cause slower proliferation, reduced cell size and asporogeny in
      Saccharomyces cerevisiae.
AB  - The introduction of CEN14-based plasmids into haploid strains of Saccharomyces
      cerevisiae resulted in reduced proliferation rates and significantly smaller
      (20%) cell size than in untransformed control cells. This could be useful to
      those yeast biotechnology processes that require high levels of gene expression
      but little or no yeast growth and proliferation. In diploids similar plasmids
      caused asporogeny, which was possibly a consequence of the reduced cell size.

PMID- 7576556
TI  - Alpha-(4-O-methyl)-D-glucuronidase activity produced by the rumen anaerobic
      fungus Piromonas communis: a study of selected properties.
AB  - The rumen anaerobic fungus Piromonas communis, unlike the rumen anaerobic fungi
      Neocallimastix frontalis and Neocallimastix patriciarum, produced extracellular
      alpha-(4-O-methyl)-D-glucuronidase when grown in cultures containing filter
      paper, barley straw, birchwood xylan or birchwood sawdust as carbon source. The
      highest concentration of enzyme was produced in cultures containing birchwood
      sawdust. The aldobiouronic acid O-alpha-(4-O-methyl-D-glucopyranosyluronic acid)
      (1-->2)-D-xylopyranose (MeGlcAXyl) was the best substrate of those tested: the
      aldotriouronic acid O-alpha-(4-O-methyl-D-glucopyranosyluronic acid (1-->2)-O
      beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (MeGlcAXyl2) and the aldotetraouronic
      acid O-alpha-(4-O-methyl-D-glucopyranosyluronic acid)-(1-->2)-O-beta-D-
      xylopyranosyl-(1-->4)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (MeGlcAXyl3)
      were also attacked but the rate fell as the degree of polymerisation increased.
      When the same substituted xylo-oligosaccharides were reduced to the corresponding
      alditols the enzyme activity disappeared. Similarly, p-nitrophenyl-alpha-D
      glucuronide was not a substrate. Remarkably, the relative rates of attack shown
      by the alpha-(4-O-methyl)-D-glucuronidase on the aldouronic acids and on xylans
      extracted from birchwood, oat spelts and oat straw differed according to the
      carbon source used to produce the enzyme. The alpha-(4-O-methyl)-D-glucuronidase
      had a pH optimum of 5.5 and a temperature optimum of 50 degrees C. On gel
      filtration the enzyme was shown to be associated with proteins covering the range
      100-300 kDa, but a major peak of activity in the column effluent appeared to have
      a molecular mass of 103 kDa.

PMID- 7576558
TI  - The influence of physicochemical effects on the microbial degradation of
      chlorinated biphenyls.
AB  - The influence of different forms of substrate administration (either through the
      vapour phase or the liquid phase) on growth of two bacterial strains on biphenyl,
      2-chlorobiphenyl, and 3,5-dichlorobiphenyl has been investigated. During growth
      with all three compounds, the availability of the substrate for the cells turned
      out to be the growth-limiting factor, even in liquid culture with excess
      substrate supplied to the medium. Growth on biphenyl and 2-chlorobiphenyl could
      be greatly enhanced if the substrate was distributed on a folded filter providing
      a large surface, which was placed in the vapour phase of the culture flask. This
      was not possible in the case of 3,5-dichlorobiphenyl. Here growth accelerated
      after accumulation of a yellow meta cleavage product. Through measurement of the
      surface tension it was shown that this yellow compound possessed detergent-like
      activities, increasing the amount of 3,5-dichlorobiphenyl dissolved in the
      medium.

PMID- 7576557
TI  - 3-Methylaspartate ammonia-lyase from a facultative anaerobe, strain YG-1002.
AB  - 3-Methylaspartase was purified 24-fold and crystallized from the crude extract of
      the cells of a facultative anaerobic bacterium from soil, strain YG-1002. The
      molecular mass of the native enzyme was about 84 kDa and that of the subunit was
      about 42 kDa. The pH optimum for the deamination reaction of (2S, 3S)-3
      methylaspartic acid and those for the amination reaction of mesaconic acid were
      9.7 and 8.5; its optimum temperature was 50 degrees C. The enzyme was stable at
      pH 5.5-11.0 and up to 50 degrees C. The enzyme required both divalent and
      monovalent cations such as Mg2+ and K+. The enzyme was inhibited by sulfhydryl
      reagents, metal-chelating reagents and some divalent cations. The enzyme
      catalyzed the reversible amination/deamination reactions between several 3
      substituted (S)-aspartic acids and their corresponding fumaric acid derivatives.
      The enzyme preferentially acted on (2S, 3S)-3-methylaspartic acid and mesaconic
      acid in the deamination and the amination reactions respectively. The enzyme
      showed high similarities in several enzymological properties and N-terminal amino
      acid sequence with 3-methylaspartase from an obligate anaerobic bacterium
      Clostridium tetanomorphum.

PMID- 7576559
TI  - Complete degradation of tetrachloroethene by combining anaerobic dechlorinating
      and aerobic methanotrophic enrichment cultures.
AB  - Degradation of tetrachloroethene (perchloroethylene, PCE) was investigated by
      combining the metabolic abilities of anaerobic bacteria, capable of reductive
      dechlorination of PCE, with those of aerobic methanotrophic bacteria, capable of
      co-metabolic degradation of the less-chlorinated ethenes formed by reductive
      dechlorination of PCE. Anaerobic communities reductively dechlorinating PCE,
      trichloroethene (TCE) and dichloroethenes were enriched from various sources. The
      maximum rates of dechlorination observed for various chloroethenes in these batch
      enrichments were: PCE to TCE (341 mumol l-1 day-1), TCE to cis-dichloroethene
      (159 mumol l-1 day-1), cis-dichloroethene to chloroethene (99 mumol l-1 day-1)
      and trans-dichloroethene to chloroethene (22 mumol l-1 day-1). A mixture of these
      enrichments was inoculated into an anoxic fixed-bed upflow column. In this column
      PCE was converted mainly into cis-1,2-dichloroethene, small amounts of TCE and
      chloroethene, and chloride. Enrichments of aerobic methanotrophic bacteria were
      grown in an oxic fixed-bed downflow column. Less-chlorinated ethenes, formed in
      the anoxic column, were further metabolized in this oxic methanotrophic column.
      On the basis of analysis of chloride production and the disappearance of
      chlorinated ethenes it was demonstrated that complete degradation of PCE was
      possible by combining these two columns. Operation of the two-column system under
      various process conditions indicated that the sensitivity of the methanotrophic
      bacteria to chlorinated intermediates represented the bottle-neck in the
      sequential anoxic/oxic degradation process of PCE.

PMID- 7576560
TI  - Diversity of anaerobic microbial processes in chlorobenzoate degradation:
      nitrate, iron, sulfate and carbonate as electron acceptors.
AB  - The utilization of monochlorobenzoate isomers (2-, 3- and 4-chlorobenzoate) by
      anaerobic microbial consortia in River Nile sediments was systematically
      evaluated under denitrifying, Fe-reducing, sulfidogenic and methanogenic
      conditions. Loss of all three chlorobenzoates was noted in denitrifying cultures;
      furthermore, the initial utilization of chlorobenzoates was fastest under
      denitrifying conditions. Loss of 3-chlorobenzoate was seen under all four
      reducing conditions and the degradation of chlorobenzoates was coupled
      stoichiometrically to NO3- loss, Fe2+ production, SO4(2-) loss or CH4 production,
      indicating that the chlorobenzoates were oxidized to CO2. To our knowledge, this
      is the first observation of halogenated aromatic degradation coupled to Fe
      reduction.

PMID- 7576561
TI  - Catabolism of 2,4,6-trinitrotoluene by Mycobacterium vaccae.
AB  - Mycobacterium vaccae strain JOB-5 cometabolized 2,4,6-trinitrotoluene (TNT) in
      the presence of propane as a carbon and energy source. Two novel oxidized
      metabolites, as well as several known reduced products, were generated during
      catabolism of TNT by M. vaccae. During the cometabolic process, there was
      transient production of a brown chromophore. This compound was identified as 4
      amino-2,6-dinitrobenzoic acid. When M. vaccae was incubated with [14C]TNT and
      propane, 50% of the added radiolabel was incorporated into the cellular lipid
      fraction. These results suggest that ring cleavage occurred prior to the
      incorporation of radiolabelled carbon into phosphatidyl-L-serine,
      phosphatidylethanolamine, cardiolipin, and other polar lipids.

PMID- 7576562
TI  - Nutrient-enhanced survival of and phenanthrene mineralization by alginate
      encapsulated and free Pseudomonas sp. UG14Lr cells in creosote-contaminated soil
      slurries.
AB  - The effects of nutrient amendment and alginate encapsulation on survival of and
      phenanthrene mineralization by the bioluminescent Pseudomonas sp. UG14Lr in
      creosote-contaminated soil slurries were examined. UG14Lr was inoculated into
      creosote-contaminated soil slurries either as a free cell suspension or
      encapsulated in alginate beads prepared with montmorillonite clay and skim milk.
      Additional treatments were free-cell-inoculated slurries amended with sterile
      alginate beads, free-cell-inoculated and uninoculated slurries amended with skim
      milk only, and uninoculated, unamended slurries. Mineralization was determined by
      measuring 14CO2 released from radiolabelled phenanthrene. Survival was measured
      by selective plating and bioluminescence. Inclusion of skim milk was found to
      enhance both survival of and phenanthrene mineralization by free and encapsulated
      UG14Lr cells.

PMID- 7576563
TI  - Substrate availability in phenanthrene biodegradation: transfer mechanism and
      influence on metabolism.
AB  - The mechanism of phenanthrene transfer to the bacteria during biodegradation by a
      Pseudomonas strain was investigated using a sensitive respirometric technique
      (Sapromat equipment) allowing the quasi-continuous acquisition of data on oxygen
      consumption. Several systems of phenanthrene supply, crystalline solid and
      solutions in non-water-miscible solvents (silicone oil and 2,2,4,4,6,8,8
      heptamethylnonane) were studied. In all cases, analysis of the kinetics of oxygen
      consumption demonstrated an initial phase of exponential growth with the same
      specific growth rate. In order to analyze the second phase of growth and
      phenanthrene degradation, a study of the kinetics of phenanthrene transfer to the
      aqueous phase was conducted by direct experimentation, with the crystal and
      silicone oil systems, in abiotic conditions. The data allowed the validation of a
      model based on phase-transfer laws, describing the variations, with substrate
      concentrations, of rates of phenanthrene transfer to the aqueous phase. Analysis
      of the biodegradation curves then showed that exponential growth ended in all
      cases when the rates of phenanthrene consumption reached the maximal transfer
      rates. Thereafter, the biodegradation rates closely obeyed, for all systems, the
      transfer rate values given by the model. These results unambiguously demonstrated
      that, in the present case, phenanthrene biodegradation required prior transfer to
      the aqueous phase. With the silicone oil system, which allowed high transfer and
      biodegradation rates, phenanthrene was directed towards higher metabolite
      production and lower mineralization, as shown by oxygen consumption and carbon
      balance determinations.

PMID- 7576564
TI  - Pathology of the thymus: changes induced by xenobiotics and gene targeting.
AB  - Studies on the thymus in pathologic conditions have been of great help in the
      elucidation of the function of the organ in T-cell development. The first
      examples come from congenital immunodeficiency states in man and laboratory
      animals. A number of toxic substances affect different components of the thymus
      already at exposure levels where there is no effect on the peripheral immune
      system. In some cases, this thymotoxic effect has been causally related to
      defects in the peripheral immune system (immunodeficiency and autoimmunity). In
      recent years immunodeficient states have been created in mouse by disruption of
      genes coding immunologically relevant molecules. Studies on such gene 'knock-out'
      mice have shown that a number of molecules are indispensable for appropriate T
      cell development at different stages in the thymus, whereas others are
      dispensable. It is concluded that the experimental approach combining gene
      targeting and exposure to thymotoxic xenobiotics will present interesting tools
      for further studies in thymus research.

PMID- 7576565
TI  - Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ.
AB  - Surgical specimens from 62 patients with vulvar dysplasia and carcinoma in situ
      were morphologically investigated. Lesions were classified according to WHO
      (mild, moderate, severe dysplasia and carcinoma in situ) and according to Toki et
      al. (1991) (warty, basaloid, combined warty/basaloid or basaloid/warty types or
      mixed (warty, basaloid and simple) forms). Following the WHO classification,
      moderate dysplasia was shown in 4 cases, severe dysplasia in 47 and carcinoma in
      situ in 11 cases. Pure warty type was shown in 2 cases (both biopsy specimens).
      One case revealed pure simple dysplasia whereas no case of pure basaloid type was
      found. Various combinations of warty and basaloid types were shown in 52 cases
      and mixed forms in 7 cases. The results indicate that pure forms of warty and
      basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases
      (88%) (45 with HPV type 16 and 6 with HPV type 33) evenly distributed in all age
      groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was
      detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33),
      nearly always in warty areas. All these cases were positive for the same virus
      type by PCR. No case revealed more than one type of HPV. HPV type 6, 11, 18, and
      31 were not detected by PCR. The results indicate a correlation between HPV type
      16 and 33 and dysplasia/carcinoma in situ in the vulva.

PMID- 7576566
TI  - Interobserver agreement for tumour type, grade of differentiation and stage in
      endometrial carcinomas.
AB  - The histopathologic evaluation plays a major role in subdividing endometrial
      carcinomas into treatment groups. We have evaluated the interobserver agreement
      regarding tumour type, grade of differentiation, stage and stage I low and high
      risk cases. A total of 177 cases of endometrial carcinoma in which a hysterectomy
      and a bilateral salpingo-oophorectomy were performed, were reviewed by three
      examiners. A variety of features including tumour type, architectural grade,
      nuclear grade, FIGO grade, and spread/metastases were recorded, and the FIGO
      stage was determined. Using two different definitions low and high risk groups in
      stage I tumours were separated. A kappa value was calculated for each of the
      various parameters. The current study showed a good strength of agreement for
      tumour type, myometrial invasion, spread/metastases, and FIGO stage (kappa 0.62
      1.00). For two of the examiners good agreement was found as to architectural
      grade (kappa 0.71) while the kappa value for nuclear grade was lower (0.56). As
      nuclear grading is included in the revised FIGO recommendation a precise
      definition of nuclear atypia is needed. In stage I tumours very good agreement
      was demonstrated as to the defined low and high risk group (Kappa 0.64-0.86).

PMID- 7576567
TI  - HLA antigens in ulcerative colitis and primary sclerosing cholangitis.
AB  - The aims of this study were to find out whether the alleles of the HLA class I or
      II region are associated with susceptibility to ulcerative colitis, and to show
      whether there is a difference or similarity in HLA associations between primary
      sclerosing cholangitis and ulcerative colitis. HLA-A, B, C and DR antigens were
      studied using the standard lymphocyte microcytotoxicity test in 24 Finnish
      patients with primary sclerosing cholangitis, 77 patients with ulcerative
      colitis, and 106 controls. HLA-B8 (54%) and DR3 (60%) were associated with
      primary sclerosing cholangitis. HLA-DR1 (46%) and DR6 (20%) seemed more common in
      ulcerative colitis than in controls. A positive association with Cw7 was common
      to both ulcerative colitis (25%) and primary sclerosing cholangitis (33%). Our
      results indicate that ulcerative colitis is more heterogeneous than primary
      sclerosing cholangitis in its HLA-DR associations.

PMID- 7576568
TI  - Six billion neurons lost in AIDS. A stereological study of the neocortex.
AB  - Human immunodeficiency virus type 1 (HIV1) is neurotropic. One of the
      morphological changes that is seen in patients with acquired immunodeficiency
      syndrome (AIDS) is cerebral atrophy affecting various structures including the
      neocortex. The cause of atrophy is not known. The total number of neocortical
      neurons was estimated in formalin fixed brains of 12 males with AIDS and 12 male
      controls matched for age and height. The mean number of neocortical neurons was
      16.0 x 10(9) (coefficient of variation = 0.11) in the AIDS patients compared with
      21.9 x 10(9) (coefficient of variation = 0.22) in the controls, a difference of
      approximately six billion (p < 0.005, 2-tailed). The global neuronal loss was
      37%, and affected all four neocortical lobes. Ten patients did not have a history
      of central nervous system symptoms; two patients had a history of dementia. The
      number of neurons in the AIDS cases was not associated with dementia. AIDS is the
      first disease in which a global loss of neocortical neurons has been demonstrated
      using unbiased stereological methods. The loss of more than one third of the
      neurons may partly explain the cortical atrophy. Focal neuron loss has been
      reported by several authors, but none have been based on unbiased methods. In
      this group of AIDS patients the severe loss of neurons did not correspond to
      neurological deficits.

PMID- 7576569
TI  - A time-related study of Brefeldin A effects in HSV-1 infected cultured human
      fibroblasts.
AB  - Glycoprotein D (gD-1) is an essential virion envelope component of herpes simplex
      virus type 1 (HSV-1) normally transported to the plasma membrane of the infected
      cells. In the present study, the intracellular transport of gD-1 was inhibited in
      cultured HSV-1 infected human fibroblasts by Brefeldin A (BFA) 1 microgram/ml
      medium added for 12 h after virus adsorption. Immunofluorescence light- and
      confocal microscopy revealed abolished transport of gD-1 to the plasma membrane,
      juxtanuclear accumulation of gD-1, and a disorderly arrangement of the tubulin
      fibres. Withdrawal of BFA influence for more than 60 min resulted in incomplete
      transport but increasing accumulation of gD-1 in the plasma membrane and in Golgi
      like areas close to the nuclei. The tubulin pattern was almost normalized 6 h
      after removal of BFA. The egress of infectious HSV-1 particles released 9 h post
      BFA treatment was not fully reestablished. The results indicate that BFA effects
      were not completely reversible and caused a sort of cytotoxic influence involving
      the structure of tubulin.

PMID- 7576570
TI  - Development of a peroxidase-antiperoxidase (PAP) technique for the identification
      of Haemophilus somnus in pneumonic calf lungs in Denmark.
AB  - A peroxidase-antiperoxidase (PAP) technique was developed for the identification
      of Haemophilus somnus bacteria in lung tissues of calves. Antisera raised against
      somatic and wall antigens of a Danish and American strain of H. somnus were
      produced. Experimentally infected murine tissues were used for the determination
      of the sensitivity and specificity of antiserum that had been heterologously
      absorbed with antigens of cross-reacting bacteria, i.e. Pasteurella haemolytica
      and Pasteurella multocida. None of the antisera reacted with Actinomyces
      pyogenes. An antiserum raised against somatic antigens of the Danish strain of H.
      somnus revealed the highest sensitivity in the PAP technique and became specific
      following absorption. Heterologous absorption also rendered this antiserum
      specific in crossed immunoelectrophoresis. Subsequently, the PAP technique was
      applied on formalin-fixed pneumonic lung tissues of 86 calves. An immunodiagnosis
      of H. somnus pneumonia was obtained in 15 of 17 lungs from which the bacterium
      had been isolated. Moreover, immunostained bacteria were also demonstrated in 20
      lungs from which H. somnus had not been isolated. Thus, application of
      immunohistochemistry significantly enhanced the diagnostic sensitivity of H.
      somnus pneumonia of calves and should be used as a potent supplementary tool for
      the routine screening of suspected lung tissues of calves from which bacterial
      isolation is negative.

PMID- 7576572
TI  - Beta 2-microglobulin expression of AIDS-related and classical Kaposi's sarcoma.
AB  - The expression of beta 2-microglobulin, the invariable light chain of HLA class I
      molecules, of Kaposi's sarcoma from 11 AIDS patients and from 11 patients without
      known immunodeficiency was studied by immunohistochemistry using a polyclonal
      antibody to beta 2-microglobulin. The staining intensity of spindle cells in
      these lesions was scored in a semiquantitative system. We found that the spindle
      cells of Kaposi's sarcomas from AIDS patients showed significantly increased
      staining intensity for beta 2-microglobulin compared to those of Kaposi's
      sarcomas from non-AIDS patients. The results may indicate that Kaposi's sarcomas
      developing in immunocompromised individuals, such as AIDS patients, are not
      subject to immune selection by T cells eliminating HLA class I high-expressing
      tumor cells, while this may be the case in non-AIDS patients. Alternatively, the
      results may be caused by differences in the activity of cytokines, which
      upregulate the expression of HLA class I molecules on the cell surface.

PMID- 7576571
TI  - Sertoli cells of intratubular germ cell neoplasia express beta 2 microglobulin.
AB  - The cells in intratubular germ cell neoplasia in the vicinity of 38 germ cell
      tumors of the testis, including 20 pure seminomas, were studied for the
      expression of beta 2-microglobulin (beta 2m), the constant component of all HLA
      class I molecules. Immunohistochemistry using antibodies towards beta 2m,
      vimentin, placental alkaline phosphatase, and ferritin was employed. Whereas the
      intratubular cells in normal testis are beta 2m negative, beta 2m positive cells
      were identified in intratubular germ cell neoplasia tubules in 55 per cent of all
      tumors and in 60 per cent of the seminomas. The tubules with beta 2m positive
      cells were located in areas with invasive tumor or in the vicinity of such areas.
      The beta 2m positive cells were identified as Sertoli cells by morphology and by
      their staining with anti-vimentin. Neoplastic germ cells, identified by
      morphology and staining with anti-placental alkaline phosphatase and anti
      ferritin were beta 2-microglobulin negative. The most intensely beta 2m-stained
      Sertoli cells were found in tubules with high concentrations of neoplastic germ
      cells. Intensely stained Sertoli cells were also found in 'Sertoli cell only'
      tubules inside invasive tumors and in areas without lymphocytic infiltration. The
      cells in adjacent normal tubules were beta 2m negative.

PMID- 7576574
TI  - Metallothionein expression in placental tissue in Menkes' disease. An
      immunohistochemical study.
AB  - Menkes' disease is a recessive X-linked disturbance of copper metabolism,
      resulting in accumulation of copper in several extra-hepatic tissues including
      the placenta. Metallothionein (MT) is a low-molecular weight protein with a high
      affinity for group II metal ions, such as copper. Its synthesis is induced by the
      presence of the ions. The aim of this study was to investigate the pattern of the
      MT immunoreactivity in placental tissue obtained from women at-risk of Menkes'
      disease in order to examine whether the MT occurrence and distribution may
      reflect the copper content. Placental tissue from six women with a family history
      of Menkes' disease, from 4 women without a family history, and from 2 hydatiform
      moles was studied. Positive MT immunostaining was found to be independent of the
      length of fixation, whether the tissue samples were fixed in 4% buffered
      formaldehyde or Bouin's fixative. The avidin-biotin-complex (ABC)-technique was
      used. The copper content was measured by neutron activation analysis (NAA). In
      all placental tissue sections positive MT immunostaining appeared only in the
      trophoblast and only in proliferating cells. In placental tissue sections
      obtained from foetuses and children affected by Menkes' disease an additional MT
      immunostaining appeared in the Hofbauer cells of the chorionic villi. This
      staining was associated with an increased content of copper as measured by NAA.
      We conclude that the immunohistochemical demonstration of MT reflects the copper
      content and may be useful in pre- and postnatal diagnosis of Menkes' disease.

PMID- 7576573
TI  - Thomsen-Friedenreich (T) antigen as marker of myoepithelial and basal cells in
      the parotid gland, pleomorphic adenomas and adenoid cystic carcinomas. An
      immunohistological comparison between T and sialosyl-T antigens, alpha-smooth
      muscle actin and cytokeratin 14.
AB  - Controversy centres on the role and identification of myoepithelial (MEC) and
      basal cells in salivary gland tumours, and recent studies suggest that both basal
      cells and myoepithelial cells participate in the formation of salivary gland
      tumours. We have correlated the expression of different well-known markers of
      normal MEC/basal cells (i.e. alpha-smooth muscle actin and cytokeratin 14) with T
      (Thomsen-Friedenreich) antigen and its sialylated derivative: sialosyl-T
      antigen,) in 17 normal parotid glands and in two tumour types with MEC
      participation (i.e pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC))
      using immunohistology with well-defined monoclonal antibodies (MAbs). Paraffin
      embedded/fresh frozen tissue sections were studied from 33/17 patients with PA
      and 15/7 patients with ACC. In normal parotid tissue coexpression of alpha-smooth
      muscle actin, cytokeratin 14, T and sialosyl-T antigens was found in all MEC and
      in some of the basal cells lining striated ducts. The remaining basal cells
      exclusively expressed cytokeratin 14, T and sialosyl-T antigens. In the tumours,
      cells believed to be modified myoepithelial cells showed two different staining
      patterns: 1) Coexpression of alpha-smooth muscle actin, cytokeratin 14, T and
      sialosyl-T antigens, and 2) Coexpression of cytokeratin 14, T and sialosyl-T
      antigens, but no alpha-smooth muscle actin. The epithelial ductular structures in
      the tumours showed aberrant expression of cytokeratin 14, T and sialosyl-T
      antigens, and cytokeratin 14 was the only marker of cells in solid
      undifferentiated areas of adenoid cystic carcinomas. Our study supports the view,
      that modified "myoepithelial" cells in the tumours consist of a mixture of basal
      cells and myoepithelial cells. None of the investigated structures was in itself
      an ideal marker in the identification of MEC/basal cells. The cells can be
      identified by a combination of markers (i.e. cytokeratin 14, alpha-smooth-muscle
      actin, T and sialosyl-T antigens).

PMID- 7576575
TI  - Postmortem axial skeletal radiography can reveal fetal CNS malformations.
AB  - The routinely performed autopsy of a macerated fetus will often be of dubious
      value, particularly as regards the examination of the central nervous system
      (CNS). Former studies have demonstrated a close relationship between certain CNS
      malformations and axial skeletal malformations revealed radiographically. In the
      present report a postmortem examination of a severely macerated fetus
      demonstrates a transsphenoidal encephalocele. A supplementary histological
      examination confirmed this condition and furthermore revealed absence of the
      pituitary gland. The findings were related to a strongly elevated serum
      alphafetoprotein level in the 18th gestational week. This report emphasizes the
      value of postmortem axial skeletal radiography of autolyzed fetuses suspected for
      CNS malformations.

PMID- 7576576
TI  - Dissemination in athymic nude mice of lacZ transfected small cell lung cancer
      cells identified by X-gal staining.
AB  - The small cell lung cancer cell lines GLC-2 and DMS 456 were genetically labeled
      with the lacZ gene and examined for invasive and metastatic potential in META/Bom
      nude mice. The lacZ gene encodes the enzyme beta-D- galactosidase, and cells
      expressing this enzyme were identified by staining with the chromogenic substrate
      X-gal. lacZ expressing cells were investigated after subcutaneous (s.c.)
      inoculation and intravenous (i.v.) injection. The X-gal detection of beta-D
      galactosidase activity proved to be a rapid and easy means for specific and
      highly sensitive identification of metastases. All primary s.c. tumors stained by
      X-gal. The primary tumors of GLC-2 regularly demonstrated local invasive growth
      and produced multiple metastases in several organs. In contrast, primary DMS 456
      tumors only occasionally demonstrated local invasion and very rarely generated
      secondary foci. No experimental metastases were found after i.v. injection of the
      examined tumor lines. The results indicate an intratumoral heterogeneity among
      individual SCLC tumors in the capacity for invasion and metastatic spread. The
      different metastatic pattern of GLC-2 after s.c. and i.v. inoculation supports
      the hypothesis that initial steps of the metastatic cascade occurring in the
      primary tumor are necessary for the subsequent production of growing metastases.

PMID- 7576578
TI  - Expression of the intercellular adhesion molecule-3 (ICAM-3) in human renal
      tissue with relation to kidney transplants and various inflammatory diseases.
AB  - Adhesion molecules are important for immune regulatory mechanisms concerning
      antigen presentation, lymphocyte activation, localisation and migration as well
      as effector-target cell interactions in inflammatory processes. The
      immunohistochemical expression of ICAM-3, a recently cloned new member of the
      immunoglobulin family which also binds leucocyte function antigen 1 (LFA-1), was
      examined in 80 needle core biopsies from 35 renal allografts, 7 patients with
      mesangioproliferative glomerulonephritis, 5 patients with extracapillary
      glomerulonephritis, 4 patients with interstitial nephritis and 5 patients with
      diabetic nephropathy and 20 normal kidneys. In all types of lesions ICAM-3 was
      constitutively expressed on the majority of infiltrating leucocytes without
      detectable upregulation or presentation on possible target structures during
      inflammation indicating its possible role to be mainly in initiation of the
      inflammatory response.

PMID- 7576577
TI  - Morphometric studies on treated and untreated heterotransplanted malignant
      tumours.
AB  - Short-term therapy effects on heterotransplanted tumours are important to know in
      order to study the action of anticancer treatment. They are, however, difficult
      to assess due to interference from such factors as edema, vascular swelling and
      necrosis. Non-invasive methods such as NMR can be of some use, but the
      applicability is limited since background noise from the host animal organism may
      confound measurements. We studied a series of Cisplatine-treated bladder
      carcinomas heterotransplanted to nude mice and their untreated controls in order
      to illustrate short-term chemotherapy effect. We applied simple unbiased
      morphometric methods on formalin-fixed and paraffin-embedded material in order to
      obtain an unbiased estimate of the volume of the whole tumour and the volume of
      vital tumour tissue on day 1 and day 3 after treatment, at which time no gross
      changes in tumour size were evident. Furthermore, we estimated the number of
      tumour cells in the tumours. The estimate was based on measurement of the mean
      nuclear volume and the nuclear volume fraction in combination with the measured
      volume of vital tissue in the tumour. The pronounced therapy effects seen in this
      experimental system may be of potential interest in monitoring effects at the
      clinic.

PMID- 7576579
TI  - Primary paraganglioma of the lung. Report of two cases and review of the
      literature.
AB  - Two cases of primary paragangliomas of the lung are presented. The first occurred
      in a 69-year-old woman and was a grossly and histologically benign tumour. The
      other case occurred in a 33-year-old woman who had metastases to the
      peribronchial lymph nodes. This seems to be the second malignant case reported.
      No evidence of recurrence nor metastatic disease was found at follow-up, 8 months
      for the first case and 7 years for the second, respectively. The morphological
      and immunohistochemical findings are discussed and the literature comprising 20
      cases is reviewed.

PMID- 7576580
TI  - A case of cerebral paragonimiasis in Denmark. Case report.
AB  - A case of cerebral paragonimiasis with severe neurological symptoms is presented.
      The patient, a 45-year-old woman, recovered completely after resection of a large
      cyst at the C3 level. The pathogenesis is discussed.

PMID- 7576581
TI  - Tonsillar carcinoma.
AB  - Carcinoma of the tonsil is the second most common malignancy of the head and
      neck. Various studies have attempted to define the presentation, diagnosis,
      treatment, and prognosis of these tumors. This report reviews the currently
      available information on tonsillar carcinoma and discusses treatment options.

PMID- 7576582
TI  - An analysis of the Adour-Swanson and House-Brackmann grading systems for facial
      nerve recovery.
AB  - Lack of uniformity in reporting facial nerve recovery in patients with facial
      nerve paralysis has been a major disadvantage in comparing treatment modalities.
      To remove subjectivity from the analysis, we devised a facial paralysis recovery
      profile as a system for measuring facial motion. This profile has been used since
      1968 at Kaiser Permanente Medical Center, Oakland, California. The House facial
      paralysis grading system was introduced in 1983 for clinical use and was modified
      by Brackmann in 1985. This latter system has since been accepted by the American
      Academy of Otolaryngology-Head and Neck Surgery in the United States as the
      standard used in reporting results. In a prospective study of 54 patients, we
      tested multiple parameters that affect accurate reporting. We tested reliability
      and accuracy of facial measurements by using 30 control subjects and 3
      independent examiners. We used Pearson correlation coefficients to statistically
      analyze results. To compare our system with the House-Brackmann grading system,
      we measured facial motions of 24 patients randomly selected from our data bank.
      All had incomplete returns of facial function and facial defects associated with
      faulty regeneration of a partially denervated facial nerve. Our overall results
      show defects in the House-Brackmann system which should be addressed. We offer
      the Adour-Swanson grading system as a reliable, easy-to-use, suitable alternative
      to the House-Brackmann system.

PMID- 7576583
TI  - Synaptic connections and putative functions of the dopaminergic innervation of
      the guinea pig cochlea.
AB  - We report our findings in the guinea pig involving dopamine in postsynaptic
      regulation of the activity of glutamatergic inner hair cells (IHCs) and in
      protection of primary auditory neurons during transient ischemia. Seven days
      after intracochlear perfusion of 6-hydroxydopamine, no immunoreactivity to
      tyrosine hydroxylase (TH) was demonstrable within the organ of Corti. TH and
      aromatic amino acid decarboxylase were immunolocalized at an ultrastructural
      level within lateral olivocochlear varicosities synapsing with radial auditory
      dendrites postsynaptic to the IHCs. The D2 agonist piribedil induced a dose
      dependent decrease in the amplitude of the compound action potential of the
      auditory nerve. Piribedil also prevented appearance of ischemia-induced swelling
      of the radial dendrites.

PMID- 7576584
TI  - Selecting the best tone-pip stimulus-envelope time for estimating an objective
      middle-latency response threshold for low- and middle-tone sensorineural hearing
      losses.
AB  - The effects of rise-fall and plateau times for the Pa component of the middle
      latency response (MLR) were investigated in normally hearing subjects, and an
      objective MLR threshold was measured in patients with low- and middle-tone
      hearing losses, using a selected stimulus-envelope time. Our results showed that
      the stimulus-envelope time (the rise-fall time and plateau time groups) affected
      the Pa component of the MLR (quality was determined by the (chi 2-test and
      amplitude by the F-test). The 4-2-4 tone-pips produced good Pa quality by visual
      inspection. However, our data revealed no statistically significant Na-Pa
      amplitude differences between the two subgroups studied when comparing the 2- and
      4-ms rise-fall times and the 0- and 2-ms plateau times. In contrast, Na-Pa became
      significantly smaller from the 4-ms to the 6-ms rise-fall time and from the 2-ms
      to the 4-ms plateau time (paired t-test). This result allowed us to select the 2-
      or 4-ms rise-fall time and the 0- or 2-ms plateau time without influencing
      amplitude. Analysis of the stimulus spectral characteristics demonstrated that a
      rise-fall time of at least 2ms could prevent spectral splatter and indicated that
      a stimulus with a 5-ms rise-fall time had a greater frequency-specificity than a
      stimulus of 2-ms rise-fall time. When considering the synchronous discharge and
      frequency-specificity of MLR, our findings show that a rise-fall time of four
      periods with a plateau of two periods is an acceptable compromise for estimating
      the objective MLR threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576585
TI  - Neuroendocrine neoplasms of the larynx. Importance of the correct diagnosis and
      differences between atypical carcinoid tumors and small-cell neuroendocrine
      carcinoma.
AB  - Findings in the present study have confirmed that the diagnosis of neuroendocrine
      tumors of the larynx (NETL) requires that a panel of neuroendocrine markers and
      electron microscopy be performed. This means that the clinician must be aware of
      the clinical presentations of such patients and should send fresh biopsy
      specimens to the clinical laboratory for optimal tissue studies. As shown in this
      study, the possibility of misdiagnosis of an atypical carcinoid tumor (ACT) is
      rather high. In establishing a diagnosis, a part of the material should be fixed
      for conventional histology, a part for immunohistochemistry and a part for
      electron microscopy. The correct diagnosis of NETL is obviously of great
      importance for subsequent treatment and prognosis. Patients with the diagnosis of
      ACT of the larynx require surgical treatment. Our findings also show that small
      cell neuroendocrine carcinomas of the larynx should be considered to be a
      disseminated disease at initial presentation. A metastatic workup is necessary,
      but radical surgical procedures should be avoided. The combination of
      radiotherapy and chemotherapy is always indicated.

PMID- 7576586
TI  - Expression of the c-fos transcription factor in the rat auditory pathway
      following postnatal auditory deprivation.
AB  - As an animal model for inborn hearing loss rat pups were reared in a sound-proof
      chamber from birth until age 21 days. In addition, pinnae were bilaterally
      sutured closed to reduce any influence of ambient sound. At the end of the sound
      deprivation, outer ear channels were reopened. Since previous studies failed to
      show any difference in the number or morphology of neurons in the auditory
      pathway in bilaterally sound-deprived animals, expression of c-fos protein was
      used as a functional marker to map trans-synaptic information transfer in the
      auditory pathway with cellular resolution. At day 21 sound-deprived rats and
      untreated controls were stimulated with pure tones of 8kHz for 5min at different
      sound pressure levels. Acoustic stimulation induced c-fos in both parts of the
      cochlear nucleus, superior olivary complex and inferior colliculus. Compared to
      untreated rats, deprivation reduced the number of c-fos labeled neurons in the
      dorsal and ventral part of the cochlear nucleus and inferior colliculus by 58%
      and 30%, respectively, following low sound pressure levels (90dB). In contrast,
      high sound pressure levels (120dB) increased the number of c-fos labeled neurons
      in these areas and evoked only minor differences in the number of labeled neurons
      in both untreated and sound deprived rats.

PMID- 7576588
TI  - Beta-adrenergic mechanisms in the nasal mucosa vascular bed.
AB  - In thiopentone-anesthetized mature pigs (n = 7), local intra-arterial infusion of
      the beta 2-adrenoceptor agonists terbutaline and salbutamol and the beta 3
      agonist BRL 37344 induced dose-dependent increases in nasal arterial blood flow
      (BF) and volume of the nasal mucosa (reflecting capacitance vessel function).
      Increases were also found in the laser Doppler flowmeter signal, reflecting
      superficial mucosal BF. In contrast to terbutaline and salbutamol, BRL 37344
      showed marked effects on volume. Pretreatment with the beta-adrenoceptor blocker
      propranolol significantly reduced the vasodilatory effects of terbutaline and
      salbutamol, whereas the BF increase evoked by BRL 37344 was not affected.
      Exogenous noradrenaline (NA) induced in vitro dose-dependent contractions of
      human nasal mucosa biopsies obtained from patients with non-allergic chronic
      rhinitis (n = 21) or non-allergic nasal polyposis (NANP, n = 16). On a molar
      basis, the contractile effect of NA was significantly greater in nasal mucosa
      samples without histological abnormalities when compared to biopsies with
      abundant inflammatory cells and edema within the submucosa. In the presence of
      propranolol, the vasoconstrictor effect of NA was significantly enhanced in
      biopsies with abundant inflammatory cells obtained from patients with NANP (P <
      0.01). This observation suggests the possible occurrence of a beta 2 hyper
      reactivity in the nasal mucosa of patients with NANP. After precontraction in a
      Krebs-Ringer solution with 50 nM K+, all nasal biopsies studied showed dose
      dependent relaxation to terbutaline, salbutamol and BRL 37344. This relaxant
      effect was markedly reduced after pretreatment with propranolol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576587
TI  - Characterization of sugar receptor expression by neoglycoproteins in oral and
      oropharyngeal squamous cell carcinomas.
AB  - Recognition of the carbohydrate part of cellular glycoconjugates by sugar
      receptors like lectins may contribute to biosignaling and interactions between
      normal and transformed cells. Such recognitions may be essential for establishing
      phenotypic characteristics in neoplastic cells, including metastasis-associated
      properties. To evaluate various glycoconjugates in tumor diagnosis and clinical
      therapy, a panel of 18 biotinylated neoglycoproteins was prepared. This included
      conjugates of a histochemically inert carrier protein and crucial sugar moieties
      such as D-glucuronic acid, alpha- and beta-N-acetyl-galactosamine, beta-N-acetyl
      glucosamine, melibiose, lactose, maltose, cellobiose, mannose, mannose-6
      phosphate, fucose, rhamnose, and xylose. In so doing the diazo derivative of the
      respective p-aminophenyl glycosides was coupled with galactose, beta-N-acetyl
      galactosamine or beta-N-acetyl-glucosamine via an epoxy group-containing
      aliphatic spacer. Other glycoconjugates used were the proteoglycan heparin and
      the sulfated fucan fucoidan. Labeling was effected with cyanogen bromide
      activation and aminoalkylation for specific detection of endogeneous sugar
      receptors, especially lectins. Tissues studied were paraformaldehyde-fixed,
      paraffin-embedded surgical biopsies from patients with different stages of
      squamous cell carcinomas (SCCs) of the oral cavity (n = 16) and oropharynx (n =
      17), including three lymph node metastases from oropharyngeal primary tumors.
      Semiquantitative binding differences of probes to tumor stages were evaluated
      statistically by the Mann-Whitney U-Wilcoxon rank sum W test. Specific binding of
      a probe to cytoplasmic and nuclear structures was detected with apparent
      quantitative differences. Overall, the cytoplasmic compartment revealed a higher
      intensity of histochemical reaction than did nuclear structures, indicating a
      comparatively higher density of specific carbohydrate receptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576589
TI  - Allergic rhinitis in laboratory workers caused by occupational exposure to guinea
      pigs: an immunological and clinical study.
AB  - Occupational exposure in laboratory workers to various animals can result in
      clinically significant respiratory allergies. We used clinical and immunological
      methods to study five laboratory workers who exhibited symptoms of nasal allergy
      upon occupational exposure to guinea pigs. As compared with a control group of
      ten nonallergic laboratory workers, the symptomatic workers generally had
      positive skin test reactions for allergens derived from the urine, saliva, and
      pelts of the guinea pigs. The study group with symptoms also showed high serum
      levels of specific IgE and demonstrated an immediate, positive reaction to nasal
      provocation testing with urine-derived antigen. However, specific IgG values in
      the sera of these patients did not differ significantly from control values.
      Overall results indicated that a type 1 allergy was involved.

PMID- 7576590
TI  - Autoregulation of cochlear blood flow in young and aged mice.
AB  - Autoregulation is the capacity of an organ system to maintain organ blood flow
      constant in response to changes in arterial blood pressure (BP). The current
      study was carried out to investigate the effect of age on autoregulation of
      cochlear blood flow (CBF) in mice. CBF was measured using a laser-Doppler
      flowmeter while BP was increased by angiotensin II injections and decreased by
      exsanguination in 2-month-old, 10-month-old and 18-month-old CBA mice.
      Autoregulation of CBF was significantly weaker in the 2-month-old mice when
      compared to the older mice. Although CBF autoregulation was weaker in the 18
      month-old mice compared to the 10-month-old mice, this difference was not
      statistically significant. These results suggest that autoregulation changes with
      maturation and age. Findings are discussed in relationship to the possible
      development of presbycusis.

PMID- 7576591
TI  - Expression of S-100 protein in the human fetal inner ear.
AB  - The expression of S-100 protein was analyzed in the human fetal inner ear using
      immunohistochemical methods. In the 11-week-old human fetus, the cochlea was
      almost negative for S-100 protein, whereas in the 14- and 15-week-old fetuses,
      the spiral ligament, Reissner's membrane and spiral limbus were positive for the
      protein. These results suggest that S-100 protein may be a reliable marker for
      determining functional maturation of the fetal cochlea and the inner ear. In the
      11-, 14- and 15-week fetuses, the epithelial cells of the endolymphatic sac were
      labelled with S-100 protein. These findings demonstrate that the endolymphatic
      sac, spiral limbus and spiral ligament in the fetal inner ear have a high
      activity of S-100 protein, with this presence possibly related to fluid and ion
      transport of endolymph.

PMID- 7576592
TI  - Thyroid spindle epithelial tumor with thymus-like differentiation (the "SETTLE"
      tumor). An immunohistochemical and electron microscopic study.
AB  - An intrathyroid primary epithelial spindle-cell tumor with mucous cysts is
      described in a 9-year-old child. Histologically, this well-circumscribed tumor
      exhibited a nodular pattern, a prominent spindle cell component with minimal
      pleomorphism, and well-differentiated mucinous glands within fibrous bands. The
      spindle cells demonstrated diffuse immunopositivity for cytokeratin and vimentin.
      Electron microscopy of tissue sections demonstrated that cells contained bundles
      of cytoplasmic tonofilaments and numerous desmosomes. The light and electron
      microscopic features and immunohistochemical profile of this tumor were similar
      to those of recently described thyroid tumors that have been called "SETTLE"
      tumors (i.e., spindle epithelial tumor with thymus-like differentiation). These
      uncommon tumors can be considered intrathyroid thymoblastomas and must be
      regarded as potentially malignant lesions.

PMID- 7576593
TI  - Muscle cell function during prolonged activity: cellular mechanisms of fatigue.
AB  - Muscle performance declines during prolonged and intense activity; important
      components are a reduction in force production and shortening velocity and a
      prolongation of relaxation. In this review we consider how the changes in
      metabolites (particularly H+, inorganic phosphate (Pi), ATP and ADP) and changes
      in sarcoplasmic reticulum Ca2+ release lead to the observed changes in force,
      shortening velocity and relaxation. The reduced force is caused by a combination
      of reduced maximum force-generating capacity, reduced myofibrillar Ca2+
      sensitivity and reduced Ca2+ release. The reduced maximum force and Ca2+
      sensitivity are largely explained by the effects of H+ and Pi that have been
      observed in skinned fibres. At least three different forms of reduced Ca2+
      release can be recognized but the mechanisms involved are incompletely
      understood. The reduced shortening velocity can be partly explained by the
      effects of H+ that have been observed in skinned fibres. In addition it is
      proposed that ADP, which depresses shortening velocity, increases during
      contractions to a level that is considerably higher than existing measurements
      suggest. Changes in Ca2+ release are probably unimportant for the reduced
      shortening velocity. The prolongation of relaxation can arise both from slowing
      of the rate of decline of myoplasmic calcium concentration and from slowing of
      cross-bridge detachment rates. A method of analysis which separates these
      components is described. The increase in H+ and the other metabolite changes
      during fatigue can independently affect both components. Finally we show that
      reduced force, shortening velocity and slowed relaxation all contribute to the
      decline in muscle performance during a working cycle in which the muscle first
      shortens actively and then is stretched passively by an antagonist muscle.

PMID- 7576595
TI  - Contractile activation and measurements of intracellular Ca2+ concentration in
      cane toad twitch fibres in the presence of 2,3-butanedione monoxime.
AB  - The effects of 2,3-butanedione monoxime (BDM, 0.5-20 mM) on Ca(2+)-activated
      force in skinned muscle fibres, and force and Ca2+ responses in aequorin-injected
      intact fibres from the iliofibularis muscle of the cane toad Bufo marinus were
      investigated. Peak twitch force responses progressively decreased to 3% of the
      control response with increasing [BDM] up to 20 mM. Peak twitch aequorin light
      responses decreased to 65% of the control response in 10 mM BDM, but increased
      again to control values in 20 mM BDM. The duration of the twitch aequorin light
      response increased by up to 60% above 5 mM BDM. Tetanic (170 Hz) force and
      aequorin light responses reversibly decreased in a dose-dependent fashion to
      about 50% of the control response in 10 mM BDM. Failure of tetanic (170 Hz)
      stimulation was observed in the presence of 20 mM BDM. Intracellular [Ca2+] could
      be modified by changing the frequency of tetanic stimulation in the presence of
      BDM, permitting a study of the dependence of isometric force on intracellular
      [Ca2+] at different concentrations of BDM. In 10 mM BDM, the rate of force
      development in intact fibres was slower by a factor of two at saturating [Ca2+],
      and was up to one order of magnitude slower at non-saturating [Ca2+], when
      compared with control responses. At a similar intracellular [Ca2+] steady-state
      isometric force was reduced to about 85 and 50% of the control responses in 2 and
      10 mM BDM, respectively. The effect of BDM on maximum Ca2+-activated force in
      skinned fibres paralleled the decrease in tetanic (170 Hz) force observed in
      intact fibres. The rate of force development in skinned fibres decreased with an
      increase in [BDM] at constant [Ca2+], and the sensitivity of the contractile
      apparatus to Ca2+ was shifted to a higher [Ca2+] by BDM. The results suggest that
      BDM reduces contractility in cane toad iliofibularis muscle by direct inhibition
      of the contractile apparatus, and reduction of the release of activator Ca2+ from
      the sarcoplasmic reticulum. Furthermore, BDM may be a useful tool to help study
      the relationship between force and [Ca2+] in intact muscle fibres.

PMID- 7576594
TI  - The effects of glibenclamide on tetanic force and intracellular calcium in normal
      and fatigued mouse skeletal muscle.
AB  - In this study the effects of ATP-sensitive K+ channel modulators were studied in
      intact single fibres dissected from mouse skeletal muscle. Indo-1 was used to
      measure [Ca2+]i simultaneously with force during normal and fatiguing
      stimulation. In control fibres, opening of ATP-sensitive K+ channels with BRL
      38227 produced a small reduction in tetanic force and [Ca2+]i. In contrast,
      glibenclamide, a selective blocker of the ATP-sensitive K+ channel, slightly
      increased tetanic force and [Ca2+]i in these fibres and also increased Ca2+
      sensitivity. Glibenclamide produced a more marked increase in tetanic force and
      [Ca2+]i during the later stages of fatiguing stimulation, although this effect
      was observed in only 50% of fibres examined. We conclude from this study that
      glibenclamide produces a partial reversal of the later stages of fatigue in a
      subpopulation of muscle fibres. Opening of ATP-sensitive K+ channels may
      therefore contribute to the decline in tetanic force and [Ca2+]i characteristic
      of skeletal muscle fatigue.

PMID- 7576596
TI  - Ca2+ release channels in rat denervated skeletal muscles.
AB  - Sarcoplasmic reticulum (SR) Ca2+ release channel-ryanodine receptors (RYR1) from
      rat fast-twitch skeletal muscle were studied by incorporating heavy sarcoplasmic
      reticulum membranes into a lipid bilayer. Channels from normal and denervated
      muscles had the same conductance as that reported for rabbits (about 500 pS) in
      250:250 mM cis:trans caesium methanesulphonate. Caffeine (0.1 mM) induced a
      larger increase in the open probability (Po) in denervated than in normal
      channels. The caffeine effect was caused by changes in mean open and burst time
      distributions. Longer opening and burst events were detected in the presence of
      caffeine. High caffeine concentrations (4 mM) gave similar results in channels
      from normal and denervated muscles. In denervated muscle, unlike intact muscle,
      the Ca2+ release channel was not activated at millimolar Ca2+ concentrations;
      this is similar to the cardiac isoform of the channel. Maximal channel activation
      was shifted to higher Ca2+ concentrations (pCa 4) and the channel remained
      activated at millimolar Ca2+ concentrations. The main effect of millimolar Ca2+
      concentrations upon Ca2+ release channels from denervated muscles was an increase
      in the mean open time, with a concomitant increment of the mean burst duration.
      Alterations in channel gating properties in calcium and caffeine account for
      changes in the mechanical response after skeletal muscle denervation.

PMID- 7576597
TI  - Muscarinic suppression of Ca2+ current in smooth muscle cells of the guinea-pig
      urinary bladder.
AB  - The suppressive action of carbachol (CCh) on the Ca2+ current (ICa) in smooth
      muscle cells of the guinea-pig urinary bladder was investigated using the whole
      cell patch clamp technique. Bath application of 10 microM CCh reduced the
      amplitude of ICa by 92 +/- 3.8% (n = 9). Adding 1 microM atropine to the bath
      completely blocked the action of CCh, indicating that the suppressive action of
      CCh on ICa is mediated by the activation of muscarinic receptors. Intracellular
      perfusion of the non-hydrolysable GTP analogue, guanosine 5'-O-(3
      thiotriphosphate) (GTP gamma S; 200 microM) mimicked the effects of CCh.
      Sustained suppression of ICa was observed when GTP gamma S was present in the
      cytoplasm. Intracellular perfusion of inositol 1,4,5-trisphosphate (InsP 3; 20
      microM) also suppressed ICa; its effect was not sustained but transient. The
      protein kinase C activator, phorbol 12,13-dibutyrate (PDBu), however, could not
      mimic the effects of CCh on ICa. When intracellular Ca2+ was strongly buffered by
      the Ca2+ chelator EGTA (20 mM) in the patch pipette, the sustained suppression of
      ICa was abolished. Inclusion of 3 mg/ml heparin, a blocker of InsP3-induced Ca2+
      release, in the patch pipette reduced the degree of sustained ICa suppression by
      43.2 +/- 1.9% (n = 7). Adding thapsigargin (TG), a sarcoplasmic reticulum Ca2+
      ATPase inhibitor, to a wash solution reduced the recovery of ICa by about 50%,
      suggesting that approximately half of the ICa suppression induced by CCh is due
      to Ca2+ release from TG-sensitive internal Ca2+ stores. From these results it
      appears that CCh suppresses ICa via two independent mechanisms: (1) Ca(2+)
      mediated inactivation of the Ca2+ channel, which is caused by Ca2+ release from
      InsP3- and TG-sensitive internal stores, and (2) a GTP-binding protein-mediated
      mechanism, which requires intracellular Ca2+.

PMID- 7576598
TI  - The secretion of parathyroid hormone-related protein in the saliva of sheep and
      its effects on the salivary clearance of phosphate, calcium, magnesium, potassium
      and sodium ions.
AB  - Parathyroid hormone-related protein (PTHrP(1-34)) was infused into five sheep,
      each fitted with a large rumen cannula. After infusion, significant increases
      were observed in the total and ionized calcium concentrations in plasma but not
      in saliva. In contrast, significant decreases in the plasma concentrations of
      phosphate and potassium and corresponding increases in their salivary
      concentrations and clearance rates were observed. The salivary concentration of
      endogenous PTH1P(1-34) was significantly greater than that in plasma sampled
      simultaneously, but during the infusion of PTHrP(1-34) both plasma and salivary
      concentrations of PTHrP(1-34) increased.

PMID- 7576599
TI  - Intestinal calcium transport in mole-rats (Cryptomys damarensis and
      Heterocephalus glaber) is independent of both genomic and non-genomic vitamin D
      mediation.
AB  - The role of vitamin D in mineral uptake in the gastrointestinal tract (GIT) of
      mole-rats (Heterocephalus glaber and Cryptomys damarensis; family Bathyergidae),
      animals with a naturally impoverished vitamin D status, was investigated. We
      measured relative rates of passage of radioactive markers, mode of calcium (Ca)
      uptake, paracellular movement and the opening of voltage-sensitive Ca channels
      (VSCCs) along the GIT with and without oral vitamin D3 supplementation. The ratio
      of relative absorption of labelled 45Ca to [14C]polyethylene glycol ([14C]PEG)
      indicated that within 24 h more than 88% of the Ca in the diet had been absorbed.
      Most absorption occurred in the duodenum within 12 h. The contribution of the
      hindgut (caecum and proximal and distal colon) to total Ca absorption was small
      (approximately 11%). Only passive uptake occurred in the duodenum (serosal (S):
      mucosal (M) ratios approximately 1). Active uptake occurred in the hindgut (S:M >
      2), although hindgut absorption appears to play a secondary role to passive
      uptake in the duodenum. Vitamin D3 supplementation had no effect on the mode of
      Ca uptake in either the small intestine or the hindgut. Although we found VSCCs
      in mole-rat intestinal epithelial cells, they occurred in very low
      concentrations. Calcium influx through VSCCs did not change following vitamin D
      stimulation. Furthermore, mole-rats pretreated with intraperitoneal (I.P.)
      1,25(OH)2D3 showed no enhancement of VSCC Ca uptake, indicating that active
      uptake plays a minor role, if any, in GIT mineral absorption. Our data support
      the hypothesis that intestinal Ca transport in mole-rats is independent of both
      genomic and non-genomic vitamin D mediation.

PMID- 7576600
TI  - The endothelial and non-endothelial mechanism responsible for attenuated
      vasoconstriction in cirrhotic rats.
AB  - The pathogenesis of the vasodilatation associated with liver cirrhosis is not
      fully understood, but it has recently been postulated that it may be related to
      an increase in nitric oxide production. The aim of this study was to compare the
      response of isolated aortic rings from normal and cirrhotic rats to two
      vasoconstrictors, phenylephrine and U46619, a thromboxane analogue. Biliary
      cirrhosis was induced by ligation of the common bile duct; a sham operation was
      performed in control animals. Five weeks later, the aorta was removed and
      dissected into rings for study in organ chambers. Concentration-response curves
      were obtained for the two vasoconstrictors from rings with intact endothelium and
      from rings denuded of endothelium. We found that the vasoconstriction produced by
      phenylephrine was decreased in cirrhotic vessels both with and without
      endothelium, but the response to U46619 was not modified by cirrhosis.
      Concentration-response curves for phenylephrine were also obtained from rings in
      which the synthesis of nitric oxide and prostaglandins was inhibited by NG
      monomethyl-L-arginine and indomethacin, respectively. Nitric oxide synthase
      inhibition restored normal contractility of the rings with and without
      endothelium. This beneficial effect was not observed when cyclo-oxygenase
      activity was blocked with indomethacin. This study suggests that cirrhotic
      vessels are hyporeactive to vasoconstrictors and that this effect is mediated
      through increased nitric oxide production. The improvement observed after
      inhibition of the nitric oxide pathway in denuded rings led us to suggest that
      cirrhosis also induces nitric oxide synthase in smooth muscle cells, as
      previously observed by others in septic animals.

PMID- 7576601
TI  - A micropuncture study of the renal response to haemorrhage in rats: assessment of
      the role of vasopressin.
AB  - The acute effects of haemorrhage (15 ml (kg body wt)-1) on renal function at
      whole-kidney and single-nephron levels were studied in Inactin-anaesthetized
      rats. In order to assess the role of vasopressin in mediating the haemodynamic
      effects, responses in untreated Long-Evans rats were compared with those in
      Brattleboro rats (which lack circulating vasopressin) and in Long-Evans rats
      treated with a V1 receptor antagonist. In time-control animals, there were no
      significant changes in mean arterial pressure (MAP), excretion rates, glomerular
      filtration rate (GFR), superficial-nephron GFR (SNGFR) or fluid reabsorption in
      the superficial proximal tubules during the course of the experiment. Following
      haemorrhage, the immediate reduction in MAP was followed in each group by partial
      recovery for 30 min; thereafter, MAP was stable. In untreated Long-Evans rats,
      haemorrhage was followed by a 26% reduction in GFR (P < 0.001, measured 60-150
      min post-haemorrhage) and a larger reduction (45%, P < 0.001) in SNGFR, so that
      the SNGFR/GFR ratio fell significantly ((27.9 +/- 1.9) x 10(-6), control period;
      (20.2 +/- 2.2) x 10(-6) post-haemorrhage, P < 0.01). Slightly greater reductions
      in GFR and SNGFR were seen in Brattleboro rats and V1 antagonist-treated Long
      Evans rats, which corresponded to slightly greater haemorrhage-induced reductions
      in blood pressure in these groups; the falls in the SNGFR/GFR ratio were similar
      to that in untreated Long-Evans rats. In all three groups of bled rats,
      fractional reabsorption by the proximal convoluted tubule increased slightly 30
      60 min after haemorrhage, but during the subsequent period (60-150 min) returned
      to values indistinguishable from those during the control period. The results
      suggest that the renal haemodynamic changes that follow moderate haemorrhage
      include a preferential reduction in the GFR of superficial nephrons. Vasopressin
      appears to play no role in this response. Increases in fractional reabsorption in
      the proximal tubules are seen only during the immediate post-haemorrhage period.

PMID- 7576602
TI  - Primary neural involvement in renal haemodynamic and functional responses to
      prolonged stimulation of atrial receptors in anaesthetized dogs.
AB  - To determine the precise contributory role of neural and humoral factors in the
      efferent mechanism of the atrial receptor-renal reflex, we have examined the
      effects of prolonged (45 min) stimulation of left atrial receptors on renal
      haemodynamics and function simultaneously in both kidneys (right kidney intact
      and left kidney denervated) of anaesthetized dogs. Aortic pressure in these dogs
      was held constant by means of an arterial reservoir connected to the aorta; heart
      rate changes were prevented by blocking beta 1-adrenoceptor activity with
      atenolol (2 mg kg-1 i.v.). Localized stimulation of atrial receptors in six dogs
      increased renal blood flow (6 +/- 2%), creatinine clearance (11 +/- 4%), urine
      flow (9 +/- 3%), sodium excretion (14 +/- 7%) and osmolal excretion (10 +/- 4%),
      and decreased free water clearance (14 +/- 7%) in intact kidneys, but led to no
      changes in denervated kidneys. In an additional four dogs, cooling the vagus
      nerves to 6-7 degrees C or cutting them in the neck abolished the renal responses
      to stimulation of atrial receptors in these stabilized preparations. These data
      clearly demonstrate that the renal responses to prolonged stimulation of atrial
      receptors are primarily mediated via myelinated vagal afferents and renal
      sympathetic efferents.

PMID- 7576603
TI  - The effects of pregnancy and parturition on the substance P content of the rat
      uterus: uterine growth is accompanied by hypertrophy of its afferent innervation.
AB  - The afferent innervation of the uterus might be expected to grow during pregnancy
      as the size of the uterus increases. Substance P-like immunoreactivity (SPLI) has
      been measured as a means of monitoring the changes in the afferent innervation of
      the urogenital tract of rats during pregnancy and following parturition. The
      great growth of uterine tissue during pregnancy causes an overall decrease in
      SPLI concentrations during pregnancy, but it has been found that the amount of
      SPLI present per uterine horn increases nearly 3-fold by the end of pregnancy.
      This increase is greater in uterine horns that contain more fetuses, suggesting
      that the SPLI innervation expands to a greater extent in uterine horns that
      undergo greater degrees of hypertrophy. There is a significant correlation
      between SPLI content and the number or total weight of fetuses throughout the
      latter two-thirds of pregnancy. There is a fall in SPLI content of uterine horns
      following parturition, but not to a statistically significant degree, and this
      may be related to the release of the peptide during parturition.

PMID- 7576604
TI  - Sympathoadrenal and other endocrine and metabolic responses to hypoglycaemia in
      the fetal foal during late gestation.
AB  - In the present study, ten insulin challenge tests were carried out on nine
      chronically catheterized fetal foals between 253 and 314 days gestation (term >
      320 days). Changes in fetal plasma concentrations of glucose, catecholamines,
      cortisol, ACTH, free fatty acid (FFA) and lactate were measured before and after
      a bolus dose of insulin (0.5-2.0 u/kg I.V.). Fetal blood gases, pH, haemoglobin
      levels and heart rate were measured throughout the 2-3h experimental period. The
      fetuses fell into two distinct groups on the basis of proximity to delivery and
      basal plasma cortisol and catecholamine levels. Those within 2-10 days of
      delivery after 300 days (group 2, number of experiments (n) = 4) had plasma
      cortisol and noradrenaline concentrations which were significantly higher (P <
      0.05) than the corresponding values in fetuses sampled earlier in gestation or at
      least 2 weeks before foaling (group 1, n = 6). Although insulin administration
      resulted in a 50% fall in plasma glucose in all animals, group 2 showed
      significantly greater increases in plasma noradrenaline than group 1. In neither
      group were there detectable changes in plasma adrenaline. In group 2, increases
      in plasma cortisol were seen following insulin, whereas no cortisol changes were
      observed in group 1, despite rises in plasma ACTH. Insulin administration also
      led to acidosis and increases in heart rate and plasma lactate and FFA levels in
      all fetuses studied. However, only group 2 became consistently hypoxic during the
      insulin challenge. No significant changes in plasma glucose or any of the other
      parameters were observed in the fetuses after saline administration (n = 5).
      These findings suggest that hypoglycaemia activates the sympathoadrenal system in
      the fetal foal from 75% of gestation but has relatively little effect on the
      fetal pituitary-adrenocortical axis until much closer to term.

PMID- 7576605
TI  - Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior
      pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal
      pig.
AB  - Prepubertal pigs (n = 8) treated with bacterial endotoxin (20 micrograms
      lipopolysaccharide; LPS) exhibited a sustained (4 h) hyperthermia, increased
      plasma concentrations of cortisol, prolactin, growth hormone and vasopressin, but
      no change in adrenaline or noradrenaline levels was observed. All these effects
      were prevented or attenuated when the animals were pretreated intravenously with
      the cyclo-oxygenase inhibitor indomethacin (IND; 2 mg/kg). Similarly, in pigs (n
      = 3 per treatment) given IND, LPS or IND + LPS, parallel changes in the neuronal
      expression of c-Fos were observed in hypothalamic regions concerned with
      thermoregulation, neurohypophysial secretion, and the control of pituitary
      adrenocortical function. The stimulatory action of LPS in the median preoptic,
      supraoptic and paraventricular nuclei was prevented by IND, whereas IND given
      alone was without effect. These findings suggest that inducible cyclo-oxygenase
      pathways are responsible for the febrile and neuroendocrine effects of endotoxin
      in this species.

PMID- 7576606
TI  - Penetration of small molecular weight substances through cultured bovine brain
      capillary endothelial cell monolayers: the early effects of cyclic adenosine
      3',5'-monophosphate.
AB  - Second messengers, such as cyclic adenosine 3',5'-monophosphate (cAMP), have been
      shown to take part in the regulation of blood-brain barrier permeability. In the
      present study, elevation of cAMP levels decreased sucrose (mol. wt, 342) and
      inulin (mol. wt, 5000) permeability across monolayers of bovine brain capillary
      endothelial cells as early as 1 h after exposure. Since both tracers use
      predominantly a paracellular pathway, we assume that cAMP may increase the
      tightness of the tight junctions through protein phosphorylation.

PMID- 7576607
TI  - Expression of whey acidic protein (WAP) genes in tissues other than the mammary
      gland in normal and transgenic mice expressing mWAP/hGH fusion gene.
AB  - Whey acidic protein (WAP) is a major whey protein secreted in rodents' milk.
      Murine WAP (mWAP) genes have been assumed to be expressed solely in the mammary
      gland. However, several heterologous genes fused with the mWAP promoter and
      artificially introduced into animal genomes as transgene were expressed not only
      in the mammary gland but also in other tissues as well. In the present study, we
      investigated, by means of the reverse transcription polymerase chain reaction (RT
      PCR), the patterns of expression of endogenous WAP genes in tissues of normal
      mice and in transgenic mice carrying hGH gene coupled to the mWAP promoter
      sequence. The results revealed that the genes driven by the mWAP promoter,
      regardless of whether they are endogenous genes or transgenes, were transcribed
      in a variety of tissues other than the mammary gland of lactating normal female
      mice, although the expression levels are generally low. The expression of WAP
      genes in the cerebrum and the liver is regulated, as in the mammary gland,
      according to the reproductive stages. However, the tissue distribution of
      endogenous WAP gene expression in mature virgin transgenic female mice was the
      same as that in lactating normal female mice.

PMID- 7576608
TI  - Murine polo like kinase 1 gene is expressed in meiotic testicular germ cells and
      oocytes.
AB  - To identify key molecules that regulate germ cell proliferation and
      differentiation, we have attempted to isolate protein kinase genes preferentially
      expressed in germ line cells. One such cDNA cloned from murine embryonic germ(EG)
      cells encodes a nonreceptor type serine/threonine kinase and is predominantly
      expressed in the testis, ovary, and spleen of adult mouse. The nucleotide
      sequence of the entire coding regions shows that this clone, designated Plk1(polo
      like kinase 1), is identical with STPK13 previously cloned from murine erythro
      leukemia cells. The protein encoded by Plk1 is closely related to the product of
      Drosophila polo that plays a role in mitosis and meiosis. To define the role of
      Plk1 in germ cell development, we have examined its expression in murine gonads
      by in situ hybridization. Here we show that the Plk1 gene is specifically
      expressed in spermatocytes of diplotene and diakinesis stage, in secondary
      spermatocytes, and in round spermatids in testes. It is also expressed in growing
      oocytes and ovulated eggs. The pattern of expression of the Plk1 gene suggests
      that the gene product is involved in completion of meiotic division, and like the
      Drosophila polo protein, is a maternal factor active in embryos at the early
      cleavage stage.

PMID- 7576609
TI  - Chromatin condensation activity and cortical activity during the first three cell
      cycles of a mouse embryo.
AB  - One-cell parthenogenetic haploid embryos and blastomeres of the 2- and 4-cell
      diploid mouse embryos were observed in vitro for the occurrence of two
      cytoplasmic activities: the cortical activity and the chromatin condensation
      activity. For this purpose anucleated halves (AHs) and nucleated halves (NHs)
      were produced by bisection of one-cell embryos and of blastomeres. The cortical
      activity (manifested by surface deformations) was observed only during the first
      cleavage cycle. In AHs the surface activity began at the same time as in NHs and
      disappeared before the time of the cleavage division of nucleated halves.
      Anucleate fragments of blastomeres from 2- and 4-cell embryos did not exhibit any
      cortical activity. In the absence of the native nucleus the chromatin
      condensation activity (assayed by premature chromatin condensation of interphase
      thymocyte nuclei introduced into cytoplasts by cell fusion) could also have been
      detected only in the first cleavage cycle. In AHs this activity appeared at the
      time when NHs started to cleave and disappeared after the NHs finished the first
      cleavage division. AHs obtained from 2-cell and 4-cell stage blastomeres did not
      reveal condensation activity.

PMID- 7576610
TI  - Different transmission rates of herpesvirus thymidine kinase reporter transgenes
      from founder male parents and male parents of subsequent generations.
AB  - Previously we demonstrated that lines of transgenic mice carrying the herpes
      simplex type 1 virus thymidine kinase (HSV1-tk) reporter gene are male-sterile.
      Ectopic transcription of the HSV1-tk reporter in the testis was initiated
      downstream of the normal translation initiation codon and truncated proteins
      consistent with translational initiation at the second and third ATG codons were
      synthesized. Here we describe the effects on fertility 1) of converting the
      second and third ATG codons of the HSV1-tk reporter to CTG codons and 2) of
      utilizing the HSV type 2 thymidine kinase (HSV2-tk) reporter gene, in which the
      second ATG codon is located downstream of the ATP-binding pocket of the enzyme.
      Both reporters were coupled to the bovine thyroglobulin promoter (bTG-tk1 alpha
      and bTG-tk2 transgenes). The level of ectopic expression of these transgenes in
      the testis, relative to expression in the thyroid, was one to two orders of
      magnitude less than that of bTG-tk1. Sixty percent of male founders carrying the
      bTG-tk1 alpha and bTG-tk2 transgenes were fertile but did not transmit the
      transgene. In contrast, most males from subsequent generations were fertile and
      transmitted the transgenes at the expected frequency. This difference between
      founder males and male descendants is also observed with certain constructs in
      which the HSV1-tk reporter is coupled to other promoters. We attribute the effect
      to mosaicism among male founders, leading to competition between transgenic and
      nontransgenic spermatozoa and/or spermatogenic precursor cells and resulting in a
      lack of fertilization by transgenic sperm that would successfully fertilize eggs
      in the absence of competition.

PMID- 7576611
TI  - Molecular interactions between fibronectin and integrins during mouse blastocyst
      outgrowth.
AB  - To investigate the mechanism of trophoblast adhesion to fibronectin, we cultured
      blastocysts in serum-free medium on proteolytic fibronectin fragments containing
      its major functional domains, and localized fibronectin-binding integrins in
      outgrowing trophoblast cells by immunofluorescent staining. Outgrowth comparable
      to that obtained with intact fibronectin was observed using a 120 kD chymotryptic
      fragment containing the central cell-binding domain (FN-120) and the Arg-Gly-Asp
      (RGD) recognition sequence. A 40 kD COOH-terminal chymotryptic fragment of
      fibronectin containing both a heparin-binding region and an alternate (non-RGD)
      cell-binding site was inactive in supporting trophoblast adhesion. Three
      synthetic peptides derived from the heparin-binding domain, including the CS1
      alternate cell-binding site, were also unable to promote trophoblast cell
      adhesion. A 75 kD recombinant protein, ProNectin F, containing 13 copies of the
      cell recognition epitope of fibronectin, Val-Thr-Gly-Arg-Gly-Asp-Ser-Pro-Ala-Ser,
      vigorously supported blastocyst outgrowth. Blastocyst outgrowth was not
      significantly different when surfaces were precoated with cellular fibronectin,
      which contains an alternatively spliced type III repeat and is the form actually
      encountered in vivo. Several putative fibronectin receptors were localized in
      trophoblast outgrowths by immunofluorescent labeling. Antibodies reactive with
      integrin subunits alpha 3, alpha 5, alpha IIb, alpha v, beta 1 and beta 3, but
      not alpha 4, all bound to trophoblast cells. Antibodies raised against either the
      beta 1 or beta 3 integrin subunits significantly inhibited fibronectin-mediated
      outgrowth. These findings demonstrate the key role of the central cell-binding
      domain of fibronectin in trophoblast adhesion, and suggest four RGD-binding
      integrins, alpha 3 beta 1, alpha 5 beta 1, alpha IIb beta 3, and alpha v beta 3,
      that could mediate trophoblast adhesion in vitro and may play an important role
      during implantation.

PMID- 7576612
TI  - Localization of nucleic acids in the nucleoli of oocytes and early embryos of
      mouse and hamster: an autoradiographic study.
AB  - Mouse preovulatory oocytes, zygotes, parthenogenetically activated pronuclear
      oocytes, and early embryos, as well as hamster zygotes, were analyzed, by
      autoradiography, for the distribution of either "maternal" or newly synthesized
      RNAs. Early mouse embryos were also examined for the distribution of newly
      replicated DNA. Special attention was attributed to NLBs in oocytes or to NPBs in
      early embryos. In mouse oocytes, [5-(3)H]uridine radioactivity accumulated (after
      a 2-hr pulse in vitro, in addition to other nuclear compartments, in the central
      compact material of the NLBs. There was no cytoplasmic labeling. In all
      parthenogenetic pronuclear embryos developed from similarly labeled oocytes, this
      label was distinctly detectable in the central compact material of the NPBs; less
      intensive labeling was seen in the nucleoplasm and cytoplasm. On the contrary,
      the central compact part of the mouse NPB did not show labeling in DNA after a
      continuous culture with [6-(3)H]thymidine. In mouse and hamster pronuclear
      zygotes, convincing evidence was obtained for a lack of any newly synthesized
      nucleic acids in the compact material of NPBs using 4- to 10-hr culture with [8
      (3)H]adenosine. Based on these data, it was shown that the NLBs of oocytes or
      NPBs of early embryos probably contain RNAs synthesized during the last stages of
      antral follicle oocyte differentiation. This unique pathway of RNAs in the oocyte
      embryo system may explain the specific morphology of both oocyte and early embryo
      "nucleoli".

PMID- 7576613
TI  - Distribution of the intermediate filament proteins vimentin, keratin, and desmin
      in the bovine ovary.
AB  - The distribution of the intermediate filament (IF) proteins desmin, keratin, and
      vimentin was studied immunohistochemically in bovine ovaries. Special attention
      was paid to granulosa cells to examine possible marked changes of IF distribution
      in relation to folliculogenesis during ovarian development. Therefore, ovaries
      were used from fetuses from 3 months of gestation onward, calves, heifers, and
      cows. In all ovaries, desmin immunoreactivity was restricted to smooth muscle
      cells in blood vessel walls. Keratin appeared a characteristic of the ovarian
      surface epithelium. Co-localization of keratin and vimentin was observed in the
      epithelium of rete ovarii tubules in fetuses and calves, and in cortical cord
      epithelium and pregranulosa cells of primordial follicles in fetuses at 3-7
      months of gestation. Vimentin was demonstrated in endothelium and in fibroblasts.
      In addition, vimentin immunoreactivity was present in granulosa cells of primary,
      secondary, and antral follicles. In antral follicles, these granulosa cells
      mainly had an elongated appearance and either contained an oblong or a round
      nucleus. Those with an oblong nucleus were characteristic for atretic antral
      follicles. In nonatretic follicles, numerous vimentin immunoreactive, elongated
      granulosa cells with a round nucleus were observed, especially in the peripheral
      granulosa layer and in small ( < 3 mm in diameter) antral follicles.
      Additionally, in antral follicles, protrusions of vimentin-positive corona
      radiata cells were observed, that penetrated the zona pellucida to contact the
      oocyte. The data show that the distribution of vimentin containing IFs is
      associated with various aspects of granulosa cell activity, as mitosis, atresia,
      and intercellular transport.

PMID- 7576614
TI  - Isolation, culture, and characterization of equine oviduct epithelial cells in
      vitro.
AB  - Oviduct epithelial cells (OEC) increasingly are used to support embryonic
      development and to study gamete interactions with the female reproductive tract
      in vitro. This series of experiments was designed to characterize monolayers
      derived from oviduct epithelium. Epithelial cells harvested from the isthmus and
      ampulla of the oviducts of five estrous mares were cultured with or without the
      basal lamina extract, Matrigel. Within each group OEC were cultured in the
      presence of either estradiol-17 beta or a carrier control. All groups were
      subcultured three times. Epithelial cell morphology and function were examined by
      microscopy, analysis of secreted proteins, and immunocytochemistry. Epithelial
      cells attached more rapidly and reached confluence sooner when cultured on
      Matrigel than in uncoated wells. Cells showed variable evidence of ciliary
      activity up to 12 days in primary culture. Cells grown on Matrigel had a more
      polarized appearance in primary culture than those in uncoated wells, although no
      morphologic difference between anatomic site of origin or between steroid treated
      groups was noted. Anatomic site of origin had no effect, and steroid treatment
      had minimal effects, on patterns of secreted proteins. However, some differences
      were noted in protein secretion between cells grown with or without Matrigel.
      These data suggest that culture substrate may affect structure and function of
      OEC monolayers.

PMID- 7576615
TI  - Chromatin organization during mouse oocyte growth.
AB  - We investigated the changes in the organization of oocyte nuclear chromatin and
      nucleolar-associated chromatin throughout folliculogenesis. Zona-free oocytes
      were isolated from ovaries, grouped into seven classes according to size and
      chromatin organization, and analyzed after staining with Hoechst 33342. We show
      that oocyte differentiation from the dictyate stage to the conclusion of
      maturation is associated with either of two chromatin configurations. Initially,
      all oocytes are in the NSN configuration (nonsurrounded nucleolus oocytes;
      characterized by a Hoechst positive-chromatin pattern of small clumps forming a
      network on the nuclear surface, with a nucleolus nonsurrounded by chromatin).
      While growing some of these NSN oocytes continue their development in the NSN
      configuration, whereas others shift (from class IV on) into the SN configuration
      (surrounded nucleolus oocytes; characterized by a threadlike chromatin
      organization that may partially surround the nucleolus or project towards the
      nuclear periphery). The percentage of SN oocytes increases both with increasing
      size of the oocyte (class I-III, 10-40 microns in diameter: 100% NSN vs. 0% SN;
      class VII 70-80 microns in diameter: 47.3% NSN vs. 52.3 SN, in 4-6-week-old
      females), and with aging (class VII: 94.1% NSN vs. 5.9% SN in 2-week-old females;
      11.8% NSN vs. 8.2% SN in 56-week-old females). Further, we suggest as a working
      hypothesis that those oocytes that switch to the SN chromatin organization early
      in maturation may not be ovulated, even though this particular chromatin
      structure normally occurs just prior to ovulation.

PMID- 7576616
TI  - Localization of microfilaments during oocyte maturation of golden hamster.
AB  - The localization and changes in microfilaments (MF) during golden hamster oocyte
      maturation were examined by an immunofluorescein method and confocal laser
      scanning microscopy (CLSM). We also studied the relationship between the changes
      in MF and oocyte nuclear and cytoplasmic maturation. During in vivo maturation,
      generalized submembranous MF were found initially which gradually became more
      prominent at the site of the first polar body extrusion. However, 43.7% of the in
      vitro matured metaphase 2 stage oocytes lacked the submembranous MF structure.
      This fact may partly account for the low fertilization rate of in vitro matured
      oocytes. MF were not found in the folicular oocytes cultured in cytochalasin D
      containing medium, and metaphase-like chromosomes were located at the center of
      the oocyte and first polar body extrusion did not occur. Twenty-five percent of
      the oocytes, which were arrested at meiosis by hypoxanthine, synthesized
      submembranous MF structure although the nuclear stage of these oocytes was
      germinal vesicle. These facts suggest that MF plays a role in nuclear behavior
      but there are some differences in the changes taking place within the nucleus and
      MF. MF may play a role in oocyte cytoplasmic maturation although the details of
      this have yet to be established.

PMID- 7576617
TI  - Structural features of the abalone egg extracellular matrix and its role in
      gamete interaction during fertilization.
AB  - Abalone eggs are surrounded by a complex extracellular coat that contains three
      distinct elements: the jelly layer, the vitelline envelope, and the egg surface
      coat. In this study we used light and electron microscopy to describe these three
      elements in the red abalone (Haliotis rufescens) and ascribe function to each
      based on their interactions with sperm. The jelly coat is a spongy matrix that
      lies at the outermost margin of the egg and consists of variably sized fibers.
      Sperm pass through this layer with their acrosomes intact and then go on to bind
      to the vitelline envelope. The vitelline envelope is a multilamellar fibrous
      layer that appears to trigger the acrosome reaction after the sperm binding.
      Next, sperm release lysin from their acrosomal granules, a nonenzymatic protein
      that dissolves a hole in the vitelline envelope through which the sperm swims.
      Sperm then contact the egg surface coat, a network of uniformly sized filaments
      lying directly above the egg plasma membrane. This layer mediates attachment of
      sperm, via their acrosomal process, to the egg surface.

PMID- 7576618
TI  - UV irradiation of chromosomal DNA and its effect upon MPF and meiosis in
      mammalian oocytes.
AB  - Bovine oocytes were irradiated at germinal vesicle (GV) or metaphase II (MII)
      stage, after Hoechst staining, with chromosomally focused UV-C (254 nm) or UV-A (
      > 330 nm). UV-C irradiation at GV stage did not inhibit germinal vesicle
      breakdown (GVBD) or chromosomal condensation; spindle formation was abolished and
      maturation promoting factor (MPF) levels failed to increase. UV-A irradiation at
      GV stage caused meiotic arrest at anaphase I; MPF levels were lower than control.
      UV-C irradiation at MII stage led to subsequent abnormal parthenogenetic
      activation when MPF levels failed to decrease. A normal male but no female
      pronucleus was formed at fertilization. UV-A irradiation at MII stage also caused
      abnormal activation; MPF levels declined normally. A normal male and abnormal
      female pronucleus formed at fertilization. UV-A irradiation results have
      implications for oocyte evaluation during development using Hoechst staining. UV
      C irradiation is a potential means for oocyte enucleation in nuclear transfer.

PMID- 7576619
TI  - Localization of intracellular calcium during the acrosome reaction in ram
      spermatozoa.
AB  - Calcium was identified by a pyroantimonate-osmium fixation technique in ram
      spermatozoa undergoing a spontaneous acrosome reaction induced by incubation of
      diluted semen at 39 degrees C. Intracellular calcium was only detected in diluted
      spermatozoa and increased in amount and distribution over 4 hr At 4 hr, the
      majority of the spermatozoa displayed ultrastructural evidence of an acrosome
      reaction. Calcium was initially evident on the outer acrosomal membrane in
      multiparticulate clusters, which were seen to be located on scalloped crests of
      acrosomal membrane as fusion developed; it was also located in the region of the
      acrosomal ridge beneath the outer acrosomal membrane. Vesiculation commenced just
      anterior to the equatorial segment and proceeded anteriorly. As vesiculation
      advanced, calcium particles became associated with the periphery of the vesicles
      attached in the region of the fusion between the two membranes, but were never
      seen inside the vesicles. The equatorial segment was not labelled until much
      later in the reaction, at which time calcium particles were also evident on the
      nuclear membrane; vesiculation of the equatorial segment was also noted at this
      time. Dense labelling of the postacrosomal dense lamina was seen in all incubated
      spermatozoa. At the anterior margin of this structure the labelling was seen to
      be in a "sawtooth" arrangement. The disposition of the calcium both temporally
      and spatially is discussed in relation to its possible mechanisms in bringing
      about membrane fusion.

PMID- 7576621
TI  - Positive and negative regulators of neural fate.

PMID- 7576620
TI  - F-actin is involved in control of bovine cumulus expansion.
AB  - Previously, we showed that the gonadotropin-induced expansion of bovine cumulus
      oophorus occurs concomitantly with the rearrangement of microfilaments (MFs)
      inside cumulus cell cytoplasm (Sutovsky et al., 1993: Biol Reprod 49:1277-1287;
      Sutovsky et al., 1994: Reprod Nutr Dev 34:415-425) and that cumulus expansion in
      cattle is accompanied by the increased expression of extracellular matrix (ECM)
      glycoproteins laminin and type IV collagen as well as of their actin-linked
      membrane receptors, integrin subunits alpha-6 and beta-1 (Sutovsky and Motlik:
      1994). The present study was undertaken to determine the spatial and temporal
      relationship between cytoskeletal rearrangement and ECM synthesis during cumulus
      expansion. Using electron microscopy and confocal (LSCM) and conventional
      fluorescence microscopy, we compared the expression of the above integrins and
      ECM proteins and the rearrangement of cytoskeleton in the gonadotropin-stimulated
      bovine oocyte cumulus complexes (OCCs) with those exposed to gonadotropin
      stimulation and to ECM synthesis inhibitor 6-diazo-5-oxo-L-norleucin (DON), or MF
      disorganizing drug cytochalasin B (CB). In control OCCs, the 24-hr culture in the
      presence of follicle stimulating hormone/luteinizing hormone (FSH/LH) caused the
      expansion of cumuli oophori and an extensive rearrangement of MFs in the
      cytoplasm of cumulus cells. Concomitantly, we observed an increased deposition of
      laminin and type IV collagen in the intercellular spaces among cumulus cells. The
      redistribution of microtubules (MTs), intermediate filaments (IFs), and integrin
      chains alpha-6 and beta-1 also occurred at this time. The addition of 20
      micrograms/ml of CB prevented cumulus expansion and accumulation of laminin and
      type IV collagen in the OCCs. Moreover, cytochalasin treatment blocked the
      redistribution of MTs and IFs, and caused the disorganization of MFs and
      dispersion of integrins in cumulus cells. In contrast, the distribution of
      integrins and cytoskeletal elements was not affected when we blocked cumulus
      expansion and ECM protein accumulation by DON. These data suggest that F-actin
      acts upstream of ECM synthesis in the cascade of events leading to the expansion
      of bovine cumulus ooophorus.

PMID- 7576622
TI  - Neuronal polarity: giving neurons heads and tails.

PMID- 7576623
TI  - Flies, genes, learning, and memory.

PMID- 7576624
TI  - Involvement of LTP in memory: are we "searching under the street light"?

PMID- 7576625
TI  - Confocal imaging and local photolysis of caged compounds: dual probes of synaptic
      function.
AB  - Chemical signals generated at synapses are highly limited in both spatial range
      and time course, so that experiments studying such signals must measure and
      manipulate them in both these dimensions. We describe an optical system that
      combines confocal laser scanning microscopy, to measure such signals, with focal
      photolysis of caged compounds. This system can elevate neurotransmitter and
      second messenger levels in femtoliter volumes of single dendrites within a
      millisecond. The method is readily combined with whole-cell patch-clamp
      measurements of electrical signals in brain slices. In cerebellar Purkinje cells,
      photolysis of caged IP3 causes spatially restricted intracellular release of
      Ca2+, and photolysis of a caged Ca2+ compound locally opens Ca(2+)-dependent K+
      channels. Furthermore, localized photolysis of the caged neurotransmitter GABA
      transiently activates GABA receptors. The use of focal uncaging can yield new
      information about the spatial range of signaling actions at synapses.

PMID- 7576626
TI  - Constructing the cerebral cortex: neurogenesis and fate determination.

PMID- 7576627
TI  - Developmental defects in brain segmentation caused by mutations of the homeobox
      genes orthodenticle and empty spiracles in Drosophila.
AB  - We have studied the roles of the homeobox genes orthodenticle (otd) and empty
      spiracles (ems) in embryonic brain development of Drosophila. The embryonic brain
      is composed of three segmental neuromeres. The otd gene is expressed
      predominantly in the anterior neuromere; expression of ems is restricted to the
      two posterior neuromeres. Mutation of otd eliminates the first (protocerebral)
      brain neuromere. Mutation of ems eliminates the second (deutocerebral) and third
      (tritocerebral) neuromeres. otd is also necessary for development of the dorsal
      protocerebrum of the adult brain. We conclude that these homeobox genes are
      required for the development of specific brain segments in Drosophila, and that
      the regionalized expression of their homologs in vertebrate brains suggests an
      evolutionarily conserved program for brain development.

PMID- 7576628
TI  - Target-independent pattern specification in the olfactory epithelium.
AB  - In mammals, odors are detected by approximately 1000 different types of odorant
      receptors (ORs), each expressed by a fraction of neurons in the olfactory
      epithelium. Neurons expressing a given OR are confined to one of four spatial
      zones but are distributed randomly throughout that zone. In the olfactory bulb,
      the axons of neurons expressing different ORs synapse at different sites, giving
      rise to a highly organized and stereotyped information map. An important issue is
      whether the epithelial and bulbar maps evolve independently or are linked, for
      example, by retrograde influences of the bulb on the epithelium. Here we examined
      the onset of expression and patterning of genes encoding ORs and sensory
      transduction molecules during mouse embryogenesis and in mice lacking olfactory
      bulbs. Our results argue for an independent development of epithelial and bulbar
      maps and an early functional development that may be pertinent to pattern
      development in the olfactory bulb.

PMID- 7576629
TI  - Neurotrophins regulate dendritic growth in developing visual cortex.
AB  - Although dendritic growth and differentiation are critical for the proper
      development and function of neocortex, the molecular signals that regulate these
      processes are largely unknown. The potential role of neurotrophins was tested by
      treating slices of developing visual cortex with NGF, BDNF, NT-3, or NT-4 and by
      subsequently visualizing the dendrites of pyramidal neurons using particle
      mediated gene transfer. Specific neurotrophins increased the length and
      complexity of dendrites of defined cell populations. Basal dendrites of neurons
      in each cortical layer responded most strongly to a single neurotrophin: neurons
      in layer 4 to BDNF and neurons in layers 5 and 6 to NT-4. In contrast, apical
      dendrites responded to a range of neurotrophins. On both apical and basal
      dendrites, the effects of the TrkB receptor ligands, BDNF and NT-4, were
      distinct. The spectrum of neurotrophic actions and the laminar specificity of
      these actions implicate endogenous neurotrophins as regulatory signals in the
      development of specific dendritic patterns in mammalian neocortex.

PMID- 7576630
TI  - Characterization of the signaling interactions that promote the survival and
      growth of developing retinal ganglion cells in culture.
AB  - The signaling mechanisms that control the survival of CNS neurons are poorly
      understood. Here we show that, in contrast to PNS neurons, the survival of
      purified postnatal rat retinal ganglion cells (RGCs) in vitro is not promoted by
      peptide trophic factors unless their intracellular cAMP is increased
      pharmacologically or they are depolarized by K+ or glutamate agonists. Long-term
      survival of most RGCs in culture can be promoted by a combination of trophic
      factors normally produced along the visual pathway, including BDNF, CNTF, IGF1,
      an oligodendrocyte-derived protein, and forskolin. These results suggest that
      neurotransmitter stimulation and electrical activity enhance the survival of
      developing RGCs and raise the question of whether the survival control mechanisms
      of PNS and CNS neurons are different.

PMID- 7576631
TI  - GDNF is an age-specific survival factor for sensory and autonomic neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of two
      populations of CNS neurons: motoneurons and midbrain dopaminergic neurons. To see
      whether GDNF promotes the survival of PNS neurons, we studied embryonic chicken
      autonomic and sensory neurons in culture. We show that GDNF promotes the survival
      of sympathetic, parasympathetic, proprioceptive, enteroceptive, and small and
      large cutaneous sensory neurons. Whereas sympathetic, parasympathetic, and
      proprioceptive neurons become less responsive to GDNF with age, enteroceptive and
      cutaneous sensory neurons become more responsive. GDNF mRNA is expressed in the
      tissues innervated by these neurons, and developmental changes in its expression
      in several tissues mirror the changing responses of the innervating neurons to
      GDNF. These results show that GDNF promotes the survival of multiple PNS and CNS
      neurons and suggest that GDNF may be important for regulating the survival of
      various populations of neurons at different stages of their development.

PMID- 7576632
TI  - Molecular cloning of linotte in Drosophila: a novel gene that functions in adults
      during associative learning.
AB  - The linotte (lio) gene was identified in a screen for mutations that disrupted 3
      hr memory after olfactory associative learning, without affecting the perception
      of odors or electroshock. The mutagenesis yielded a transposon-tagged gene
      disruption, which allowed rapid cloning of genomic DNA. The lio transcription
      unit was identified via rescue of the lio1 learning/memory defect by induced
      expression of a lio+ transgene in adults. The perception of odors or electroshock
      remained normal when the lio+ transgene was expressed in these lio1 flies.
      Learning/memory remained normal when the lio+ transgene was expressed in wild
      type (lio+) flies. The lio gene produces only one transcript, the level of
      expression of which varies throughout development. Sequence analysis indicates
      that lio encodes a novel protein.

PMID- 7576633
TI  - Improvement in visual sensitivity by changes in local context: parallel studies
      in human observers and in V1 of alert monkeys.
AB  - To explore the role of primary visual cortex in contour integration, we measured
      the contextual sensitivity of human contrast thresholds and of superficial layer
      complex cells in monkey V1. An observer's contrast detection was 40% improved by
      a second suprathreshold bar; the effect was decreased as the two bars were
      separated along their axis of orientation, were displaced from colinearity, and
      had their relative orientation changed. Recordings from V1 showed that 42% of
      complex cells demonstrated facilitation for a second bar outside their classical
      receptive fields with a similar dependency on relative location and orientation.
      Both effects were eliminated by an orthogonal line between the two iso-oriented
      lines. Multiple randomly placed and oriented lines in the receptive field
      surround often caused a reduction in a cell's response to an optimally oriented
      stimulus, but this inhibition could be eliminated by changing the orientation of
      a few of these elements to colinearity with the centrally located target.

PMID- 7576634
TI  - Activin A and follistatin expression in developing targets of ciliary ganglion
      neurons suggests a role in regulating neurotransmitter phenotype.
AB  - The avian ciliary ganglion contains choroid neurons that innervate choroid
      vasculature and express somatostatin as well as ciliary neurons that innervate
      iris/ciliary body but do not express somatostatin. We have previously shown in
      culture that activin A induces somatostatin immunoreactivity in both neuron
      populations. We now show in vivo that both targets contain activin A; however,
      choroid expressed higher levels of activin A mRNA. In contrast, follistatin, an
      activin A inhibitor, was higher in iris/ciliary body. Iris cell-conditioned
      medium also contained an activity that inhibited activin A and could be depleted
      with anti-follistatin antibodies. These results suggest that development of
      somatostatin is limited to choroid neurons by differential expression of activin
      A and follistatin in ciliary ganglion targets.

PMID- 7576636
TI  - Counting quanta: direct measurements of transmitter release at a central synapse.
AB  - Contradictory hypotheses regarding the nature of synaptic transmission in the CNS
      have arisen from indirect methods of quantal analysis. In this study, we directly
      count the quanta released following nerve stimulation to examine synaptic
      transmission at a fast glutamatergic synapse in the mammalian auditory brainstem.
      Our results demonstrate the relationship between spontaneous and nerve-evoked
      synaptic events, indicate that asynchronous transmitter release governs the time
      course of evoked transmission, and show that the stochastic quantal release
      process, as originally proposed at the neuromuscular junction, is highly
      conserved at this central synapse.

PMID- 7576637
TI  - Variation in GABA mini amplitude is the consequence of variation in transmitter
      concentration.
AB  - Miniature postsynaptic currents (minis) in cultured retinal amacrine cells, as in
      other central neurons, show large variations in amplitude. To understand the
      origin of this variability, we have exploited a novel form of synapse in which
      pre- and postsynaptic receptors sample the same quantum of transmitter. At these
      synapses, mini amplitudes measured simultaneously in the 2 cells show a strong
      correlation, accounting for, on average, more than half of the variance in
      amplitude. Two pieces of evidence support the conclusion that variations in the
      amount of transmitter in different quanta underlie this correlation. First,
      diazepam, which enhances GABA binding, increases mini amplitude, implying
      therefore that transmitter concentration is not saturating. Second, we show that
      amplitude distributions from all cells, even those with a small number of release
      sites, have the same shape, implying that most or all variance is intrinsic to
      each release site.

PMID- 7576635
TI  - Hippocampal long-term potentiation is normal in heme oxygenase-2 mutant mice.
AB  - We have generated mice deficient in HO-2, the major cerebral isoform of heme
      oxygenase, in order to assess the potential role of carbon monoxide as a
      retrograde messenger in hippocampal LTP. Cerebral HO catalytic activity was
      markedly reduced in the HO-2 mutant mice, yet no differences were found between
      wild types and mutants in gross neuroanatomical structure, in basal hippocampal
      synaptic transmission, or in the amount of potentiation produced by various LTP
      induction protocols. Furthermore, zinc protoporphyrin IX, an inhibitor of HO, had
      nearly identical inhibitory effects on LTP in wild-type and HO-2 mutant
      hippocampal slices. Our data indicate that carbon monoxide produced endogenously
      by HO is unlikely to be a neuromodulator required for LTP in the hippocampus.

PMID- 7576639
TI  - Purinergic inhibition of GABA and glutamate release in the thalamus: implications
      for thalamic network activity.
AB  - Adenosine is a CNS depressant with both pre- and postsynaptic actions.
      Presynaptically, adenosine decreases neurotransmitter release in the hippocampus
      but only at excitatory terminals. In the thalamus, however, we show that, in
      addition to its actions at excitatory synapses, adenosine strongly suppresses
      monosynaptic inhibitory currents both in relay cells of the thalamic ventrobasal
      complex (VB) and in inhibitory neurons of the nucleus reticularis thalami (nRt).
      A concomitant increase in transmission failures and results coefficient of
      variation analysis are both consistent with a presynaptic mechanism.
      Pharmacological manipulations support an A1 receptor-mediated process. Slow
      thalamic oscillations induced in vitro by extracellular stimulation and recorded
      with extracellular multiunit electrodes in VB and nRt are dampened by adenosine
      without affecting their periodicity. We conclude that adenosine can
      presynaptically down-regulate inhibitory postsynaptic responses in thalamus and
      exert robust antioscillatory effects, likely by synergistic depression of both
      excitatory and inhibitory neurotransmitter release.

PMID- 7576638
TI  - A novel G protein-coupled receptor mediating both vasopressin- and oxytocin-like
      functions of Lys-conopressin in Lymnaea stagnalis.
AB  - We have cloned a receptor, named LSCPR, for vasopressin-related Lys-conopressin
      in Lymnaea stagnalis. Lys-conopressin evokes Ca(2+)-dependent Cl- currents in
      Xenopus oocytes injected with LSCPR cRNA. Expression of LSCPR mRNA was detected
      in central neurons and peripheral muscles associated with reproduction. Upon
      application of Lys-conopressin, both neurons and muscle cells depolarize owing to
      an enhancement of voltage-dependent Ca2+ currents and start firing action
      potentials. Some neurons coexpress LSCPR and Lys-conopressin, suggesting an
      autotransmitter-like function for this peptide. Lys-conopressin also induces a
      depolarizing response in LSCPR-expressing neuroendocrine cells that control
      carbohydrate metabolism. Thus, in addition to oxytocin-like reproductive
      functions, LSCPR mediates vasopressin-like metabolic functions of Lys-conopressin
      as well.

PMID- 7576640
TI  - Gq alpha protein function in vivo: genetic dissection of its role in
      photoreceptor cell physiology.
AB  - Heterotrimeric G proteins mediate a variety of signaling processes by coupling
      seven-transmembrane receptors to intracellular effector molecules. The Drosophila
      phototransduction cascade is a G protein-coupled signaling cascade that utilizes
      a phospholipase C (PLC beta) effector. PLC beta has been shown to be activated by
      Gq alpha in reconstituted systems. To determine whether a Gq-like protein couples
      rhodopsin to PLC, and to study its function, we isolated a mutant defective in a
      photoreceptor-specific Gq protein, DGq. We now demonstrate that Gq is essential
      for the activation of the phototransduction cascade in vivo. We also generated
      transgenic flies expressing DGq under an inducible promoter and show that it is
      possible to manipulate the sensitivity of a photoreceptor cell by controlled
      expression of DGq. Characterization of quantum bumps in mutants expressing less
      that 1% of the levels of DGq revealed that the rhodopsin-G protein interaction
      does not determine the gain of the single photon responses. Together, these
      results provide significant insight into the role of Gq in regulating the output
      of a photoreceptor cell.

PMID- 7576641
TI  - Determinants of PKC-dependent modulation of a family of neuronal calcium
      channels.
AB  - The modulation of Ca2+ channel activity by protein kinases contributes to the
      dynamic regulation of neuronal physiology. Using the transient expression of a
      family of neuronal Ca2+ channels, we have identified several factors that
      contribute to the PKC-dependent modulation of Ca2+ channels. First, the nature of
      the Ca2+ channel alpha 1 subunit protein is critical. Both alpha 1B and alpha 1E
      channels exhibit a 30%-40% increase in peak currents after exposure to phorbol
      esters, whereas neither alpha 1A nor alpha 1C channels are significantly
      affected. This up-regulation can be mimicked for alpha 1E channels by stimulation
      of a coexpressed metabotropic glutamate receptor (type 1 alpha) through a PKC
      dependent pathway. Second, PKC-stimulated up-regulation is dependent upon
      coexpression with a Ca2+ channel beta subunit. Third, substitution of the
      cytoplasmic domain I-II linker from alpha 1B confers PKC sensitivity to alpha 1A
      channels. The results provide direct evidence for the modulation of a subset of
      neuronal Ca2+ channels by PKC and implicate alpha 1 and beta subunit interactions
      in regulating channel activity via second messenger pathways.

PMID- 7576642
TI  - An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean
      tarantula.
AB  - The Kv2.1 voltage-activated K+ channel, a Shab-related K+ channel isolated from
      rat brain, is insensitive to previously identified peptide inhibitors. We have
      isolated two peptides from the venom of a Chilean tarantula, G. spatulata, that
      inhibit the Kv2.1 K+ channel. The two peptides, hanatoxin1 (HaTx1) and hanatoxin2
      (HaTx2) are unrelated in primary sequence to other K+ channel inhibitors. The
      activity of HaTx was verified by synthesizing it in a bacterial expression
      system. The concentration dependence for both the degree of inhibition at
      equilibrium (Kd = 42 nM) and the kinetics of inhibition (kon = 3.7 x 10(4) M-1s
      1; koff = 1.3 x 10(-3) s-1), are consistent with a bimolecular reaction between
      HaTx and the Kv2.1 K+ channel. Shaker-related, Shaw-related, and eag K+ channels
      were relatively insensitive to HaTx, whereas a Shal-related K+ channel was
      sensitive. Regions outside the scorpion toxin binding site (S5-S6 linker)
      determine sensitivity to HaTx. HaTx introduces a new class of K+ channel
      inhibitors that will be useful probes for studying K+ channel structure and
      function.

PMID- 7576643
TI  - Modulation of K+ current by frequency and external [K+]: a tale of two
      inactivation mechanisms.
AB  - Voltage-activated K+ currents and their inactivation properties are important for
      controlling frequency-dependent signaling in neurons and other excitable cells.
      Two distinct molecular mechanisms for K+ channel inactivation have been
      described: N-type, which involves rapid occlusion of the open channel by an
      intracellular tethered blocker, and C-type, which involves a slower change at the
      extracellular mouth of the pore. We find that frequency-dependent cumulative
      inactivation of Shaker channels is very sensitive to changes of extracellular
      [K+] in the physiological range, with much more inactivation at low [K+]out, and
      that it results from the interaction of N- and C-type inactivation. N-type
      inactivation enhances C-type inactivation by two mechanisms. First, it inhibits
      outward K+ flux, which normally fills an external ion site and thus prevents C
      type inactivation. Second, it keeps the channel's activation gate open even after
      repolarization, allowing C-type inactivation to occur for a prolonged period.

PMID- 7576644
TI  - Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending
      on mitochondrial function.
AB  - During ischemic brain injury, glutamate accumulation leads to overstimulation of
      postsynaptic glutamate receptors with intracellular Ca2+ overload and neuronal
      cell death. Here we show that glutamate can induce either early necrosis or
      delayed apoptosis in cultures of cerebellar granule cells. During and shortly
      after exposure to glutamate, a subpopulation of neurons died by necrosis. In
      these cells, mitochondrial membrane potential collapsed, nuclei swelled, and
      intracellular debris were scattered in the incubation medium. Neurons surviving
      the early necrotic phase recovered mitochondrial potential and energy levels.
      Later, they underwent apoptosis, as shown by the formation of apoptotic nuclei
      and by chromatin degradation into high and low molecular weight fragments. These
      results suggest that mitochondrial function is a critical factor that determines
      the mode of neuronal death in excitotoxicity.

PMID- 7576645
TI  - Melatonin receptors are for the birds: molecular analysis of two receptor
      subtypes differentially expressed in chick brain.
AB  - Two receptors (CKA and CKB) of the G protein-coupled melatonin receptor family
      were cloned from chick brain. CKA encodes a protein that is 80% identical at the
      amino acid level to the human Mel1a melatonin receptor and is thus designated the
      chick Mel1a melatonin receptor. CKB encodes a protein that is 80% identical to
      the Xenopus melatonin receptor and defines a new receptor subtype, the Mel1c
      melatonin receptor, which is distinct from the Mel1a and Mel1b melatonin receptor
      subtypes. A melatonin receptor family consisting of three subtypes is supported
      by PCR cloning of distinct melatonin receptor fragments from Xenopus and
      zebrafish. Expression of CKA and CKB results in similar ligand binding and
      functional characteristics. The widespread distribution of CKA and CKB mRNA in
      brain provides a molecular substrate for the profound actions of melatonin in
      birds.

PMID- 7576647
TI  - Fear conditioning enhances short-latency auditory responses of lateral amygdala
      neurons: parallel recordings in the freely behaving rat.
AB  - The lateral nucleus of the amygdala (LA) is the first site in the amygdala where
      the plasticity underlying fear conditioning could occur. We simultaneously
      recorded from multiple LA neurons in freely moving rats during fear conditioning
      trials in which tones were paired with foot shocks. Conditioning significantly
      increased the magnitude of tone-elicited responses (often within the first
      several trials), converted unresponsive cells into tone-responsive ones, and
      altered functional couplings between LA neurons. The effects of conditioning were
      greatest on the shortest latency (less than 15 ms) components of the tone
      elicited responses, consistent with the hypothesis that direct projections from
      the auditory thalamus to LA are an important link in the circuitry through which
      rapid behavioral responses are controlled in the presence of conditioned fear
      stimuli.

PMID- 7576646
TI  - FGF signaling and target recognition in the developing Xenopus visual system.
AB  - We report that the growth cones of Xenopus retinal ganglion cells express
      fibroblast growth factor receptors (FGFRs) and that bFGF stimulates neurite
      extension from cultured retinal neurons. Furthermore, bFGF is abundant in the
      developing optic tract but is reduced in the optic tectum. To test whether FGF
      signaling plays a role in axonal guidance in vivo, bFGF was exogenously applied
      to the developing optic pathway in "exposed brain" preparations. FGF-treated
      retinal axons navigate normally through the optic tract, but the majority veer
      aberrantly at the tectal border and bypass the target. Our results implicate FGF
      signaling in target recognition and suggest that diminished levels of bFGF in the
      tectum cause arriving axons to slow their growth.

PMID- 7576648
TI  - huckebein specifies aspects of CNS precursor identity required for motoneuron
      axon pathfinding.
AB  - huckebein encodes a putative zinc finger protein expressed in a subset of
      Drosophila CNS precursors, including the NB 4-2/GMC 4-2a/RP2 cell lineage. In
      huckebein mutant embryos, GMC 4-2a does not express the cell fate marker EVEN
      SKIPPED; conversely, huckebein overexpression produces a duplicate EVEN-SKIPPED
      positive GMC 4-2a. We use Dil to trace the entire NB 4-2 lineage in wild-type and
      huckebein mutant embryos. Loss of huckebein does not affect the number, position,
      or type of neurons in the NB 4-2 lineage; however, all motoneurons show axon
      pathfinding defects and never terminate at the correct muscle. Thus, huckebein
      regulates aspects of GMC and neuronal identity required for proper motoneuron
      axon pathfinding in the NB 4-2 lineage.

PMID- 7576649
TI  - Bidirectional synaptic plasticity induced by a single burst during cholinergic
      theta oscillation in CA1 in vitro.
AB  - In standard protocols, the frequency of synaptic stimulation determines whether
      CA1 hippocampal synapses undergo long-term potentiation or depression. Here we
      show that during cholinergically induced theta oscillation (theta) synaptic
      plasticity is greatly sensitized and can be induced by a single burst (4 pulses,
      100 Hz). A burst given at the peak of theta induces homosynaptic LTP; the same
      burst at a trough induces homosynaptic LTD of previously potentiated synapses.
      Heterosynaptic LTD is produced at inactive synapses when others undergo LTP. The
      synaptic modifications during theta require NMDA receptors and muscarinic
      receptors. The enhancement is cooperative and occludes with standard LTP. These
      results suggest that the similar bursts observed during theta rhythm in vivo may
      be a natural stimulus for inducing LTP/LTD.

PMID- 7576650
TI  - Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal
      neurons.
AB  - Simultaneous somatic and dendritic recordings were made from the same neocortical
      layer V pyramidal neuron, and current injection via the dendritic recording
      pipette was used to simulate the voltage change that occurs during an EPSP. At
      the soma, these simulated EPSPs increased nonlinearly with the amplitude of the
      dendritic current injection and with depolarization of the membrane potential.
      Bath application of the sodium channel blocker TTX decreased large (> 5 mV) EPSPs
      and also blocked amplification of EPSPs at depolarized membrane potentials,
      whereas calcium channel blockers had little effect. Local application of TTX to
      the soma and axon blocked EPSP amplification, whereas dendritic application had
      little effect. Simultaneous somatic and axonal recordings demonstrated that EPSP
      amplification was largest in the axon. These results show that EPSPs are
      amplified by voltage-activated sodium channels located close to the soma and in
      the axon.

PMID- 7576651
TI  - Localization and functional significance of the Na+/Ca2+ exchanger in presynaptic
      boutons of hippocampal cells in culture.
AB  - Immunocytochemical evidence for localized distribution of the Na+/Ca2+ exchange
      protein in nerve terminals of cultured hippocampal cells is presented together
      with results on the functional relevance of the exchanger in the control of
      [Ca2+]i and of synaptic vesicle recycling. The monoclonal antibody R3F1, directed
      against an epitope on the intracellular loop of the protein, revealed higher
      densities of expression in synaptic regions than in other parts of the neurons.
      Removal of extracellular Na+ produced enhanced and prolonged elevation of [Ca2+]i
      in nerve terminals during and after electrical stimulation of the cells.
      Correspondingly, initial rates of exocytosis, measured by fluorescence changes of
      FM 1-43 during stimulation, were faster in LiCl-containing solution than in NaCl
      containing solution. By contrast, endocytosis at 20 s was the same in both
      solutions.

PMID- 7576652
TI  - Docked granules, the exocytic burst, and the need for ATP hydrolysis in endocrine
      cells.
AB  - Ca(2+)-triggered exocytosis was studied in single rat melanotrophs and bovine
      chromaffin cells by capacitance measurements. Sustained exocytosis required
      MgATP, but even in the absence of MgATP, Ca2+ could trigger exocytosis of 2700
      granules in a typical melanotroph and of 840 granules in a chromaffin cell.
      Granules undergoing ATP-independent exocytosis were similar in number to those
      appearing docked to the plasmalemma in quickly frozen unfixed sections (3300 in a
      melanotroph and 830 in a chromaffin cell). Most exocytosis required tens of
      seconds, but a small pool of granules was released in tens of milliseconds.
      Evidently, only a small subset of docked granules is rapidly releasable. We
      suggest that, temporally, the last ATP-dependent step in exocytosis is closely
      associated with docking and that docked granules reach fusion competence only
      after subsequent steps.

PMID- 7576653
TI  - Asynchronous release of synaptic vesicles determines the time course of the AMPA
      receptor-mediated EPSC.
AB  - The contribution of intersynaptic transmitter diffusion to the AMPA receptor EPSC
      time course was studied in cultured CA1 hippocampal neurons. Reducing release
      probability 20-fold with cadmium did not affect the time course of the averaged
      AMPA receptor EPSC, even when receptor desensitization was blocked by
      cyclothiazide, suggesting that individual synapses contribute independently to
      the AMPA receptor-mediated EPSC. Deconvolution of the averaged miniature EPSC
      from the evoked EPSC showed that release probability decays only slightly faster
      than the EPSC, suggesting that the AMPA receptor EPSC time course is determined
      primarily by the asynchrony of vesicle release. Further experiments demonstrated
      that cyclothiazide, previously thought to affect only AMPA receptor kinetics,
      also enhances synaptic release.

PMID- 7576654
TI  - Glycine-independent and subunit-specific potentiation of NMDA responses by
      extracellular Mg2+.
AB  - Extracellular Mg2+, which blocks NMDA channels in a voltage-dependent manner and
      increases the receptor's affinity for glycine, is shown here to potentiate NMDA
      responses at saturating glycine concentrations. This potentiation, induced by
      millimolar concentrations of Mg2+, is not mimicked by Ca2+ and Ba2+ and is
      voltage independent. The potentiation is variable in native receptors of cultured
      mouse central neurons; in recombinant receptors, it is "permitted" by the NR2B
      subunit and prevented by the NR1 splice variant containing an N-terminal insert.
      Mg2+ also induces a shift of the pH sensitivity of NMDA receptors. The similarity
      and nonadditivity of the effects of Mg2+ and spermine suggest that Mg2+ may be
      the physiological agonist acting at the subunit-specific spermine site.

PMID- 7576655
TI  - Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions.
AB  - Ca2+ channels display remarkable selectivity and permeability, traditionally
      attributed to multiple, discrete Ca2+ binding sites lining the pore. Each of the
      four pore-forming segments of Ca2+ channel alpha 1 subunits contains a glutamate
      residue that contributes to high-affinity Ca2+ interactions. Replacement of all
      four P-region glutamates with glutamine or alanine abolished micromolar Ca2+
      block of monovalent current without revealing any additional independent high
      affinity Ca2+ binding site. Pairwise replacements of the four glutamates excluded
      the hypothesis that they form two independent high-affinity sites. Systematic
      alterations of side-chain length, charge, and polarity by glutamate replacement
      with aspartate, glutamine, or alanine weakened the Ca2+ interaction, with
      considerable asymmetry from one repeat to another. The P-region glutamate in
      repeat I was unusual in its sensitivity to aspartate replacement but not
      glutamine substitution. While all four glutamates cooperate in supporting high
      affinity interactions with single Ca2+ ions, they also influence the interaction
      between multiple divalent cations.

PMID- 7576656
TI  - Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated
      inwardly rectifying K+ channel is important for channel activation.
AB  - Activation of G protein-gated K+ channels by G protein-coupled receptors
      contributes to parasympathetic regulation of heart rate in the atrium and
      inhibitory postsynaptic potentials in the peripheral and central nervous system.
      Having found that G beta gamma activates the cloned GIRK1 channel, we now report
      evidence for direct binding of G beta gamma to both the N-terminal hydrophilic
      domain and amino acids 273-462 of the C-terminal domain of GIRK1. These direct
      interactions are physiologically important because synthetic peptides derived
      from either domain reduce the G beta gamma binding as well as the G beta gamma
      activation of the channel. Moreover, the N-terminal domain may also bind trimeric
      G alpha beta gamma, raising the possibility that physical association of G
      protein-coupled receptors, G proteins, and K+ channels partially accounts for
      their compartmentalization and hence rapid and specific channel activation by
      receptors.

PMID- 7576657
TI  - Identification of structural elements involved in G protein gating of the GIRK1
      potassium channel.
AB  - Chimeras of GIRK1 and IRK1, a G protein-insensitive inward rectifier, are
      activated by coexpression of G beta gamma if they contain either the N-terminal
      or part of the C-terminal hydrophilic domain of GIRK1. The N-terminal domain of
      GIRK1 also facilitates the fast rates of activation and deactivation following m2
      muscarinic receptor stimulation. The hydrophobic core of GIRK1 (M1-H5-M2) is
      important for determining the brief single-channel open times typical of GIRK1
      but not important for determining G beta gamma sensitivity. Coexpression with CIR
      revealed that the gating properties associated with different GIRK1 domains could
      not have arisen from altered ability to form heteromultimers. These results
      implicate specific regions of GIRK1 in G protein activation and suggest that
      GIRK1 may be closely linked to the m2 muscarinic receptor-G protein complex.

PMID- 7576658
TI  - Identification and molecular localization of a pH-sensing domain for the inward
      rectifier potassium channel HIR.
AB  - Inward rectifier potassium channels are found in the heart and CNS, where they
      are critical for the modulation and maintenance of cellular excitability. We
      present evidence that the inward rectifier potassium channel HIR is modulated by
      extracellular pH in the physiological range. We show that proton-induced changes
      in HIR single-channel conductance underlie the HIR pH sensitivity seen on the
      macroscopic level. We used chimeric and mutant channels to localize the molecular
      determinant of HIR pH sensitivity to a single residue, H117, in the M1-to-H5
      linker region. This residue provides a molecular context that allows a titratable
      group to influence pore properties. We present evidence that this titratable
      group is one of two cysteines located in the M1-to-H5 and H5-to-M2 linkers.

PMID- 7576659
TI  - Topology of the pore-region of a K+ channel revealed by the NMR-derived
      structures of scorpion toxins.
AB  - The architecture of the pore-region of a voltage-gated K+ channel, Kv1.3, was
      probed using four high affinity scorpion toxins as molecular calipers. We
      established the structural relatedness of these toxins by solving the structures
      of kaliotoxin and margatoxin and comparing them with the published structure of
      charybdotoxin; a homology model of noxiustoxin was then developed. Complementary
      mutagenesis of Kv1.3 and these toxins, combined with electrostatic compliance and
      thermodynamic mutant cycle analyses, allowed us to identify multiple toxin
      channel interactions. Our analyses reveal the existence of a shallow vestibule at
      the external entrance to the pore. This vestibule is approximately 28-32 A wide
      at its outer margin, approximately 28-34 A wide at its base, and approximately 4
      8 A deep. The pore is 9-14 A wide at its external entrance and tapers to a width
      of 4-5 A at a depth of approximately 5-7 A from the vestibule. This structural
      information should directly aid in developing topological models of the pores of
      related ion channels and facilitate therapeutic drug design.

PMID- 7576660
TI  - Neuron-specific expression of a hamster prion protein minigene in transgenic mice
      induces susceptibility to hamster scrapie agent.
AB  - To study the effect of cell type-restricted hamster PrP expression on
      susceptibility to the hamster scrapie agent, we generated transgenic mice using a
      1 kb hamster cDNA clone containing the 0.76 kb HPrP open reading frame under
      control of the neuron-specific enolase promoter. In these mice, expression of
      HPrP was detected only in brain tissue, with highest levels found in neurons of
      the cerebellum, hippocampus, thalamus, and cerebral cortex. These transgenic mice
      were susceptible to infection by the 263K strain of hamster scrapie with an
      average incubation period of 93 days, compared to 72 days in normal hamsters. In
      contrast, nontransgenic mice were not susceptible to this agent. These results
      indicate that neuron-specific expression of the 1 kb HPrP minigene including the
      HPrP open-reading frame is sufficient to mediate susceptibility to hamster
      scrapie, and that HPrP expression in nonneuronal brain cells is not necessary to
      overcome the TSE species barrier.

PMID- 7576661
TI  - CAG expansion affects the expression of mutant Huntingtin in the Huntington's
      disease brain.
AB  - A trinucleotide repeat (CAG) expansion in the huntingtin gene causes Huntington's
      disease (HD). In brain tissue from HD heterozygotes with adult onset and more
      clinically severe juvenile onset, where the largest expansions occur, a mutant
      protein of equivalent intensity to wild-type huntingtin was detected in cortical
      synaptosomes, indicating that a mutant species is synthesized and transported
      with the normal protein to nerve endings. The increased size of mutant huntingtin
      relative to the wild type was highly correlated with CAG repeat expansion,
      thereby linking an altered electrophoretic mobility of the mutant protein to its
      abnormal function. Mutant huntingtin appeared in gray and white matter with no
      difference in expression in affected regions. The mutant protein was broader than
      the wild type and in 6 of 11 juvenile cases resolved as a complex of bands,
      consistent with evidence at the DNA level for somatic mosaicism. Thus, HD
      pathogenesis results from a gain of function by an aberrant protein that is
      widely expressed in brain and is harmful only to some neurons.

PMID- 7576662
TI  - Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing
      Alzheimer amyloid precursor proteins.
AB  - Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid
      precursor protein (APP695) die early and develop a CNS disorder that includes
      neophobia and impaired spatial alternation, with diminished glucose utilization
      and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at
      death decrease with increasing levels of brain APP. HuAPP transgenes induce death
      much earlier than MoAPP transgenes expressed at similar levels. No extracellular
      amyloid was detected, indicating that some deleterious processes related to APP
      overexpression are dissociated from formation of amyloid. A similar clinical
      syndrome occurs spontaneously in approximately 20% of nontransgenic mice when
      they reach mid- to late-adult life, suggesting that APP overexpression may
      accelerate a naturally occurring age-related CNS disorder in FVB/N mice.

PMID- 7576663
TI  - The genetics of brain development: conserved programs in flies and mice.

PMID- 7576664
TI  - Neurotrophic factors and synaptic plasticity.

PMID- 7576665
TI  - period and timeless tango: a dance of two clock genes.

PMID- 7576666
TI  - Molecular mechanisms controlling calcium entry through AMPA-type glutamate
      receptor channels.

PMID- 7576667
TI  - A collection of cortical crescents: asymmetric protein localization in CNS
      precursor cells.

PMID- 7576668
TI  - The site of expression of NMDA receptor-dependent LTP: new fuel for an old fire.

PMID- 7576669
TI  - Postoperative hemodynamic and thermoregulatory consequences of intraoperative
      core hypothermia.
AB  - STUDY OBJECTIVE: To evaluate the postoperative hemodynamic and thermoregulatory
      consequences of intraoperative core hypothermia. DESIGN: Prospective, randomized
      clinical trial. SETTING: Operating room and postanesthesia care unit of a
      university hospital. PATIENTS: 74 healthy, ASA status I, II, and III patients
      (average age 58 yrs) undergoing elective colon surgery. INTERVENTIONS: Patients
      were randomly assigned to be kept normothermic or approximately 2.5 degrees C
      hypothermic during surgery. Anesthesia was maintained with isoflurane, nitrous
      oxide, and fentanyl. Postoperatively, surgical pain was treated with patient
      controlled analgesia (PCA) opioid. MEASUREMENTS AND MAIN RESULTS: An observer
      blinded to group assignment and core temperatures evaluated shivering, thermal
      comfort, surgical pain, heart rates (HRs), and blood pressures (BPs) during the
      first six postoperative hours. Morphometric characteristics, oxygen saturation,
      fluid balance, PCA-administered opioid, and visual analog pain scores were
      comparable in the two groups. Hypothermic patients felt uncomfortably cold during
      recovery, and their postoperative core temperatures remained significantly less
      than in the normothermic patients for more than four hours. Peripheral
      vasoconstriction and shivering were common in the hypothermic patients but rare
      in those kept normothermic. HRs and BPs were comparable in the two groups.
      CONCLUSIONS: These data confirm that the effects of intraoperative hypothermia on
      postoperative HR and BP are modest in relatively young, generally healthy
      patients. In contrast, intraoperative hypothermia caused substantial
      postoperative thermal discomfort, and full recovery from hypothermia required
      many hours. Delayed return to care normothermia apparently resulted largely from
      postoperative thermoregulatory impairment.

PMID- 7576670
TI  - Use of esophageal or precordial stethoscopes by anesthesia providers: are we
      listening to our patients?
AB  - STUDY OBJECTIVE: To ascertain current anesthesia utilization of esophageal and
      precordial stethoscopes in U.S. anesthesia training programs. DESIGN:
      Prospective, single-blind, incidence study. SETTING: Operating rooms of three
      tertiary care hospitals with major academic anesthesiology departments. SUBJECTS:
      Anesthesia faculty [MD and certified registered nurse-anesthetist (CRNA) staff]
      and anesthesia trainees (anesthesiology residents and student nurse
      anesthetists). INTERVENTIONS: observe and record the placement (stethoscope
      device appropriately positioned) and utilization (stethoscope in place and
      connected to the ear piece of the anesthesia provider) of the esophageal or
      precordial stethoscope during general, regional, and monitored anesthesia care.
      MEASUREMENTS AND MAIN RESULTS: During 520 anesthetics, an esophageal stethoscope
      was inserted in 68% of subjects, a precordial stethoscope was positioned in 16%,
      and an anesthetic stethoscope was absent in 16% of cases. Utilization
      (stethoscope connected to earpiece) ranged from a low of 11% of cases to a high
      of 45%, depending on the institution. Overall, providers were listening via an
      anesthetic stethoscope in only 28% of anesthetics. CONCLUSIONS: Our data suggest
      infrequent utilization of esophageal and precordial stethoscopes in anesthesia
      training institutions. Thus, current anesthesia training may be fostering an
      environment where providers overlook a valuable minimally invasive, and cost
      effective continuous monitor of patients' dynamic vital organ function.

PMID- 7576671
TI  - A study of radiologic imaging techniques and airway grading to predict a
      difficult endotracheal intubation.
AB  - STUDY OBJECTIVES: To study whether a detailed radiographic examination of neck
      and upper airway can help identify normal looking patients in whom endotracheal
      intubation may be difficult; determine whether such parameters as identified by
      magnetic resonance imaging (MRI) can also be identified in a soft tissue
      radiograph; and to study the correlation between oropharyngeal appearance, based
      on Mallampati's classification, and laryngoscopic findings in a large number of
      patients requiring endotracheal intubation. DESIGN: Prospective. SETTING:
      University medical center. PATIENTS: 20 adult patients in whom an unanticipated
      difficult endotracheal intubation was encountered, and a control group of 20
      patients in whom endotracheal intubation was easily accomplished. INTERVENTIONS:
      Difficult-to-intubate patients were identified according to prospectively
      established criteria. Control subjects, in whom the trachea was easily intubated,
      were matched for age, gender, height, weight, and oropharyngeal appearance.
      MEASUREMENTS AND MAIN RESULTS: In all 40 study patients, a soft tissue radiograph
      and an MRI scan of the neck were obtained. We measured 21 parameters from both
      radiographic studies. There were no significant differences between the two
      groups in 20 of 21 measured parameters on MRI scans and soft tissue radiographs.
      Only one measurement--the distance between the uppermost visible part of the
      airway and the posterior pharyngeal wall (measured from MRI scans only)--between
      the two groups achieved statistical significance. The values recorded from MRI
      and soft tissue radiographs were not significantly different. Airway grading
      system first suggested by Mallampati had a fair correlation with laryngoscopy
      findings associated with a difficult endotracheal intubation. CONCLUSIONS: No
      significant difference between the two groups could be identified on soft tissue
      radiography or MRI scans.

PMID- 7576673
TI  - Pre-induction skin-surface warming minimizes intraoperative core hypothermia.
AB  - STUDY OBJECTIVE: To test the hypothesis that only one hour of preinduction skin
      surface warming decreases the rate at which core hypothermia develops during the
      first hour of anesthesia. DESIGN: Randomized, prospective study. SETTING:
      Operating theater of a university hospital. PATIENTS: 16 ASA status I and II
      adult patients scheduled for laparoscopic cholecystectomy under general
      anesthesia. INTERVENTIONS: Eight patients were assigned to receive forced-air
      warming for one hour before induction of anesthesia (prewarmed group); the other
      eight patients were covered only with a wool blanket during a similar
      preinduction period (control group). MEASUREMENTS AND MAIN RESULTS: Tympanic
      membrane (core) and mean skin-surface temperatures were measured at 15-minutes
      intervals, starting one hour before induction of anesthesia. Mean skin
      temperature increased from 34.0 +/- 0.1 C to 37.0 +/- 0.2 degrees C in the pre
      warmed group (p < 0.05), but remained unchanged at 34.7 +/- 0.3 degrees C in the
      control group. Core temperature during the preinduction period did not change
      significantly in either group. Following induction of anesthesia, core
      temperature decreased at a rate of 1.1 +/- 0.1 degrees C/hr in the control group,
      but only 0.6 +/- 0.1 degrees C/hr in the pre-warmed group (p < 0.05). After one
      hour of anesthesia, six of eight pre-warmed patients had core temperatures of at
      least 36.5 degrees C, whereas only one of the eight control patients did (p <
      0.05). CONCLUSIONS: A single hour of preoperative skin-surface warming reduced
      the rate at which core hypothermia developed during the first hour of anesthesia.
      Preoperative skin surface warming is particularly helpful during short procedures
      because redistribution hypothermia is otherwise difficult to treat.

PMID- 7576674
TI  - Spinal phobia: survey results of patient attitudes and preferences regarding
      anesthesia.
AB  - STUDY OBJECTIVE: To determine unbiased patient preferences for either spinal or
      general anesthesia for upcoming surgeries. DESIGN: Prior to contact with
      anesthesia personnel, a simple questionnaire was completed by surgical patients
      to determine their demographic characteristics and previous anesthetic
      experiences. Their concerns regarding a list of complications of general and
      spinal anesthesia and their preferences for general or spinal anesthesia if
      either method could be used were also determined. SETTING: University-affiliated
      suburban community hospital. MEASUREMENTS AND MAIN RESULTS: The survey was
      completed by 254 patients. A preference for general over spinal anesthesia was
      expressed by 80.2% of the patients responding. They expressed significantly more
      concerns regarding nausea/vomiting, sore throat, feeling sleepy, and death with
      general anesthesia than with spinal anesthesia. Concerns of back pain, nerve
      damage and paralysis were statistically related to spinal anesthesia.
      CONCLUSIONS: This survey shows a strong patient preference for general anesthesia
      and a phobia for spinal anesthesia.

PMID- 7576675
TI  - Saline soaked pledgets prevent carbon dioxide laser-induced endotracheal tube
      cuff ignition.
AB  - STUDY OBJECTIVE: To determine whether saline soaked pledgets would protect the
      cuffs of polyvinylchloride (PVC) endotracheal tubes from carbon dioxide (CO2)
      laser-induced combustion. DESIGN: 12 PVC endotracheal tubes were studied. The
      cuffed end of each was placed in a graduated cylinder and flushed with 5 L/min of
      oxygen for 5 minutes. The endotracheal tube's cuff was then inflated with air and
      the system pressure set to 20 cm H2O. SETTING: Research laboratory of a
      university hospital. INTERVENTIONS: Six of the endotracheal tube cuffs were
      protected with 1 inch by 3 inch saline soaked pledgets and six were left
      unprotected. A CO2 laser set to 40 watts was then fired at the cuffs.
      MEASUREMENTS AND MAIN RESULTS: All six unprotected cuffs were ignited in less
      than 1 second. No significant combustion occurred at the six pledget protected
      endotracheal tube cuffs after 1 minute of laser fire. CONCLUSIONS: Under the
      conditions of this experiment, saline soaked pledgets protected PVC endotracheal
      tube cuffs from the CO2 laser.

PMID- 7576672
TI  - Labor epidural catheter reactivation or spinal anesthesia for delayed postpartum
      tubal ligation: a cost comparison.
AB  - STUDY OBJECTIVES: To evaluate the costs and resource consumption associated with
      utilizing epidural catheters placed during labor versus spinal anesthesia for
      postpartum tubal ligation. To examine maternal demographics, anesthetic
      management variables, and time interval from delivery until surgery for
      association with epidural catheter reactivation success rate. DESIGN:
      Retrospective study. SETTING: University hospital labor and delivery center.
      PATIENTS: 120 consecutive postpartum patients with tubal ligations performed
      between June 1991 and December 1993. INTERVENTIONS: Postpartum women scheduled
      for tubal ligation with labor epidural catheters in place either had local
      anesthetic injected via the epidural catheter (n = 45) or had the catheter
      removed without reinjection and spinal anesthetic administered (n = 20). Patients
      with inadequate epidural anesthesia went on to receive spinal anesthesia. Women
      without a labor epidural catheter received spinal anesthesia (n = 55).
      MEASUREMENTS AND MAIN RESULTS: Adequate anesthesia for tubal ligation was
      achieved in 78% of women after reinjection of their epidural catheter. Operating
      room (OR) and anesthesia times were highest when epidural catheter reactivation
      was unsuccessful, intermediate when epidural catheter reactivation was
      successful, and lowest with initial spinal anesthesia (p < 0.05). The longer OR
      and anesthesia provider times associated with epidural catheter reactivation
      increased patient charges on average of $176 compared with the initial use of
      spinal anesthesia. CONCLUSIONS: Spinal anesthesia for postpartum tubal ligation
      was associated with lower anesthesia professional fees and OR charges compared
      with attempted reactivation of epidural catheters placed during labor.
      Anesthesiologists should weigh the cost advantages of spinal anesthesia against
      the small, but increased probability of headache after dural puncture.

PMID- 7576676
TI  - Comparison of sevoflurane and halothane anesthesia in children undergoing
      outpatient ear, nose, and throat surgery.
AB  - STUDY OBJECTIVE: To compare the induction, maintenance, and recovery
      characteristics of sevoflurane and halothane in pediatric ambulatory patients
      undergoing adenoidectomy with or without myringotomies (BMTs). To compare the
      hemodynamic effects of the two drugs. DESIGN: Open, randomized study. SETTING:
      University-affiliated pediatric hospital. PATIENTS: 39 ASA physical status I
      children aged 12 months to 12 years undergoing adenoidectomies with or without
      BMTs. INTERVENTIONS: Patients were randomized to receive sevoflurane or halothane
      in 60% nitrous oxide (N2O) for induction and maintenance of anesthesia. All
      patients received midazolam 0.5 mg/kg orally as premedication, as well as
      fentanyl 1 mcg/kg intravenously (i.v.) immediately following induction. Tracheal
      intubation was facilitated with mivacurium 0.2 mg/kg i.v. Anesthesia was
      maintained with an end-tidal concentration corresponding to 1 minimum alveolar
      concentration (MAC) of each drug until the end of surgery, at which time all
      anesthetic gases were discontinued simultaneously. Emergence (extubation),
      recovery (Steward score = 6), and discharge times were compared among patients in
      both groups. Heart rate (HR) and mean arterial pressure were compared at
      predetermined intervals. Additional fentanyl was administered after full recovery
      was documented for an objective pain score of at least 6. MEASUREMENTS AND MAIN
      RESULTS: Emergence from anesthesia was significantly faster (7.11 +/- 3.05
      minutes vs. 9.58 +/- 5.12 minutes) and recovery (19.89 +/- 10.07 minutes vs.
      31.08 +/- 9.81 minutes) more rapid in the sevoflurane group. However, there was
      no difference in the time to meet home discharge criteria (184 +/- 49 minutes vs.
      189 +/- 48 minutes). HR was consistently maintained at or above baseline in the
      sevoflurane group. Blood pressure was significantly more depressed after fentanyl
      administration in the halothane group. There were no significant differences in
      the incidence of postoperative vomiting between the two groups. CONCLUSION:
      Sevoflurane provides a faster anesthetic emergence and recovery than halothane in
      premedicated patients but it does not expedite meeting current home discharge
      criteria.

PMID- 7576678
TI  - Hemodynamic comparison of direct vision versus blind oral endotracheal
      intubation.
AB  - STUDY OBJECTIVE: To determine the hemodynamic response to airway manipulation and
      endotracheal intubation by comparing the direct oral method of the Macintosh
      laryngoscope to the blind oral method of the Augustine guide. DESIGN:
      Prospective, comparative, randomized study. SETTING: University medical center.
      PATIENTS: 24 ASA physical status I and II, nonpregnant female patients aged 18
      years or older, undergoing outpatient gynecologic surgery with general
      anesthesia. INTERVENTIONS: Patients were preoxygenated and received alfentanil 10
      mcg/kg five minutes prior to anesthesia induction with thiopental sodium 5 mg/kg
      and succinylcholine 1 mg/kg. Under random assignment, patients (n = 12 in each
      group) were intubated with the Macintosh laryngoscope or the Augustine guide.
      After intubation, 50% nitrous oxide and 50% oxygen and 1.5% inspired
      concentration of isoflurane were administered. MEASUREMENTS AND MAIN RESULTS:
      Oxygen saturation, heart rate (HR), and mean arterial pressure (MAP) were
      measured at baseline and at minutes 1 to 6 postinduction (time zero). Intubation
      time was defined as the interval between removal of the face mask from the
      patient's face and reconnection of the circle system airway connector after
      successful endotracheal intubation. The number of attempts and time to successful
      endotracheal intubation were noted. There was no difference between groups in
      age, weight, height, Mallampati airway class, oxygen saturation (at least 98%),
      or MAP. There was a significant difference (p < 0.01) between groups (percent
      change from baseline) in HR from minutes 1 to 4 postinduction. Time to successful
      endotracheal intubation was significantly longer (p < 0.05, mean +/- SEM) with
      the Augustine guide (91.0 +/- 15.9 seconds) than with the Macintosh laryngoscope
      (24.0 +/- 1.73 seconds). CONCLUSIONS: The Augustine guide, a new technique for
      orally intubating patients blindly and when head and neck manipulations are
      contraindicated, had less of an effect on HR compared with the Macintosh
      laryngoscope. Minimal lifting of the tongue and mandible required with the
      Augustine guide could account for the decreased HR response. The Augustine guide
      appears to be a promising new addition to the airway armamentarium and deserves
      further testing.

PMID- 7576677
TI  - Epidemiology of the adverse hemodynamic events occurring during "clonidine
      anesthesia": a prospective open trial of intraoperative intravenous clonidine.
AB  - STUDY OBJECTIVE: Determine the hemodynamic consequences of intraoperative
      clonidine during major abdominal surgery. DESIGN: Prospective open trial.
      SETTING: Teaching hospital. PATIENTS: 402 consecutive patients scheduled for
      major abdominal surgery. INTERVENTIONS: 350 consecutive patients received
      intravenous (IV) clonidine (loading dose of 4 micrograms/kg in 20 minutes at
      anesthesia induction, followed by a continuous infusion of 2 micrograms/kg/h
      until the end of surgery). Fifty-two additional patients served as controls.
      Anesthetic technique consisted of balanced anesthesia (isoflurane, fentanyl,
      atracurium). ECG, invasive arterial blood pressure (BP), expiratory PCO2 and
      pulse oximetry were continuously recorded. Hemodynamic events (HEs) were defined
      as moderate for a 20% reduction of the baseline systolic blood pressure (SBP) or
      a heart rate (HR) decreasing between 50 beats per minute (bpm) and 40 bpm. A 30%
      reduction of the baseline SBP or a HR below 40 bpm was considered an important
      HE. The rate and duration of these events were recorded from induction to
      recovery. HEs requiring a specific treatment were noted. Central venous pressure,
      volume of fluid infused, and urinary output were also recorded. MEASUREMENTS AND
      MAIN RESULTS: 21% of control patients and 31% of clonidine patients had no
      adverse HEs. A moderate reduction of the baseline BP was the most common episode
      in both groups. The incidence of the HEs (moderate and important) was similar in
      both groups but the duration HEs was significantly longer in the clonidine
      patients (p < 0.05). 40% of the control patients and 13% of the clonidine
      patients required specific management for their HEs (p < 0.05), the most common
      of which was hypotension without bradycardia. Neither coexisting pathology nor
      preoperative medications influenced the incidence of HEs. CONCLUSION: IV
      clonidine can be used routinely during anesthesia for major abdominal surgery.

PMID- 7576679
TI  - Anesthetic management of a patient with obstructive sleep apnea syndrome and
      difficult airway access.
AB  - Patients with the obstructive sleep apnea syndrome (OSAS) are predisposed to
      respiratory complications under the influence of sedative and anesthetic drugs
      because of these drugs' alternation of respiratory control with a tendency for
      upper airway collapse. Additional difficulties for airway management during
      anesthesia may arise if fixed anatomic obstacles block the upper airway. We
      present a case of a patient with OSAS scheduled for general anesthesia for nasal
      polypectomy and correction of a deviated septum. Preoperative evaluation revealed
      several factors known to be associated with difficult intubation and ventilation:
      nasal obstruction, maxillofacial malformation (micrognathia), reduced
      temporomandibular joint mobility, and obesity. An individualized strategy of
      airway management based on published standards was developed and successfully
      applied. It involved fiberoptic guided intubation through a laryngeal mask
      airway. This case illustrates the management of patients with OSAS and additional
      conditions that reduce upper airway patency.

PMID- 7576680
TI  - Local anesthesia infiltration as a cause of intraoperative tension pneumothorax
      in a young healthy woman undergoing breast augmentation with general anesthesia.
AB  - Pneumothorax may be a medical emergency. Iatrogenic pneumothorax is more common
      than all other forms of spontaneous pneumothorax, and surgical procedures
      involving the breast are a frequent setting for this. A 32-year-old, 60 kg, woman
      without any significant medical history underwent a bilateral breast augmentation
      and rhinoplasty. She underwent a routine general endotracheal anesthetic. Prior
      to surgical incision, the surgeon infiltrated the breast with lidocaine with
      epinephrine. Six hours into the surgical procedure, the patient developed
      hemodynamic compromise and was diagnosed with tension pneumothorax, which was
      treated emergently with a 14-gauge angiocatheter placed intrapleurally. The
      patient immediately returned to hemodynamic stability. This case report discusses
      iatrogenic pneumothoraces as well their most likely causes; which in this
      specific case was the injection of local anesthetic. Suggestions for prevention
      and treatment of the unusual complication are discussed.

PMID- 7576681
TI  - Antibiotic therapy and the anesthesiologist.
AB  - The anesthesiologist is frequently responsible for administering antibiotics in
      the immediate preoperative and intraoperative periods. Anesthesiologists often
      are not trained in the administration of antibiotics, which can be associated
      with both acute and long-term complications including potentiation of
      neuromuscular blocking agents, allergic reactions, and end-organ toxicity. The
      indications for perioperative antibiotics, proper method of administration, and
      occurrence and treatment of major side effects of the more commonly recommended
      prophylactic antibiotics are discussed.

PMID- 7576683
TI  - Positive end-expiratory pressure: effect on delivered tidal volume.

PMID- 7576684
TI  - A modified tracheal tube mount for sampling gases from the distal shaft of the
      laryngeal mask airway.

PMID- 7576682
TI  - Cost-effectiveness analysis of antiemetic therapy for ambulatory surgery.

PMID- 7576685
TI  - Efficiency and functional consequences of adenovirus-mediated in vivo gene
      transfer to normal and dystrophic (mdx) mouse diaphragm.
AB  - The protein dystrophin is absent in muscles of patients with Duchenne muscular
      dystrophy (DMD) as well as in mdx mice. The mdx mouse diaphragm closely resembles
      the human DMD phenotype and should serve as an appropriate model for future
      studies of dystrophin gene replacement. In this regard, recombinant adenovirus
      (AV) holds great promise as a vector for delivering a functional dystrophin gene
      to muscle. However, the use of AV is hampered by the development of an immune
      response against transduced cells, resulting in short-lived transgene expression
      as well as possible adverse effects on organ function. In the present study,
      sensitive reporter genes were employed to determine the efficiency and functional
      consequences of AV-mediated gene transfer to the diaphragm in both normal and mdx
      adult mice. One week after direct intramuscular injection of AV into the
      diaphragm, the level of transgene expression was significantly increased in mdx
      compared with normal diaphragms. In addition, small-caliber fibers (< 500
      microns2) demonstrated preferential transduction in both groups of mice. Normal
      diaphragms receiving AV exhibited a substantial reduction in maximal twitch and
      tetanic force generation, whereas no significant effect on diaphragm
      contractility was found in the mdx group at 1 wk after injection. At 1 mo after
      AV administration, however, there was a significant decrease in force production
      by both normal and mdx diaphragms. Immunosuppression with cyclosporine A over 1
      mo did not augment the level of transgene expression, but a beneficial effect on
      diaphragm force-generating capacity was observed in both groups of animals. We
      conclude the following: (1) short-term transduction of the diaphragm is more
      efficient in mdx than in normal mice; (2) AV leads to reduced force production by
      the diaphragm, with this effect being more pronounced in normal than in mdx in
      the early (but not the late) postinjection period; and (3) immunosuppressive
      therapy with cyclosporine has a partially protective effect on muscle function
      after AV administration, which is apparently unrelated to sparing of transduced
      fibers from elimination by the host immune system. These findings have important
      implications for the application of AV-mediated dystrophin gene transfer to the
      treatment of DMD.

PMID- 7576686
TI  - Innervation and function of the distal airways in the developing bronchial tree
      of fetal pig lung.
AB  - We investigated whether the airways of the lungs from 8 to 10 g fetal pigs (the
      pseudoglandular phase) have a nerve supply, are functionally innervated and
      narrow in response to electrical field stimulation and to agonists. Measurements
      of airway narrowing were made by real-time video imaging of intact isolated
      bronchial tree freed of associated parenchyma and vasculature. The distal (100 to
      300 microns lumen diameter) and terminal (approximately 25 to 50 microns lumen
      diameter) airways narrowed strongly to acetylcholine and histamine, to within 50
      to 80 microns of the base of the epithelial buds. Electrical field stimulation
      produced rapid narrowing followed by relaxation, and responses were blocked by
      atropine and tetrodotoxin, indicating a functional cholinergic innervation.
      Transient periods (3 to 5 min) of spontaneous narrowing were seen in localized
      regions of the bronchial tree which moved the lung liquid to and fro. An
      extensive nerve supply to the bronchial tree was seen after immunocytochemical
      staining of tissue whole mounts with anti-neurofilament. Nerves supplied the
      distal and terminal airways with fine branches penetrating the smooth muscle of
      the airway wall. A few fibers extended to the growing edge of the smooth muscle
      at the very base of the epithelial bud. The smooth muscle was cylindrically
      arranged around the airway wall all the way to the epithelial bud. We propose
      that onset of function of smooth muscle and its innervation occurs shortly after
      differentiation of the smooth muscle at the growing tips of the airways.

PMID- 7576688
TI  - Deformability and CD11/CD18 expression of sequestered neutrophils in normal and
      inflamed lungs.
AB  - Neutrophil (PMN) sequestration in the pulmonary microvasculature precedes the
      migration of these cells into the airspaces in inflamed lungs. Intratracheal
      instillation of the heat-killed organism Corynebacterium parvum in the rat
      induces an alveolitis in which PMN constitute 70 to 80% of the total cell count
      in the bronchoalveolar lavage (BAL). This acute alveolitis results in increased
      sequestration in the pulmonary microvasculature of 51Cr-labeled PMN when compared
      with control lungs. The aims of this study were to confirm this increased
      pulmonary PMN sequestration using unlabeled cells and to assess the function and
      adhesion molecule expression of such sequestered PMN. We counted the number of
      PMN and erythrocytes obtained by pulmonary vascular lavage (PVL) and compared the
      ratio of these two cell types in PVL and peripheral blood (PB) as a measure of
      the sequestration of PMN in the pulmonary vasculature. Compared with control
      animals, PVL in C. parvum-treated rats had higher PMN counts, which could not be
      accounted for by the PB leukocytosis. Sequestration of PMN in the pulmonary
      microvasculature depends on several factors, including the upregulation of
      adhesion molecules on both PMN and endothelial surfaces and the ability of the
      cells to deform when passing through the microcirculation. Cells obtained from
      the PVL were less deformable than PB cells in control but not in C. parvum
      treated animals. The expression of the CD18 integrin on PMN obtained from the PVL
      of C. parvum-treated animals was increased compared with cells from control
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576687
TI  - Hypersecretion of mucin in response to inflammatory mediators by guinea pig
      tracheal epithelial cells in vitro is blocked by inhibition of nitric oxide
      synthase.
AB  - Primary cultures of guinea pig tracheal epithelial cells in air/liquid interface
      were exposed to one of four agents associated with airway inflammation: the
      peptide histamine (100 microM), the lipid mediator platelet-activating factor (1
      microM), the cytokine tumor necrosis factor-alpha (15 ng/ml; specific activity
      2.86 x 10(7) U/mg), or enzymatically generated reactive oxygen species (purine
      [500 microM]+xanthine oxidase [20 mU/ml]). Effects of each of these substances on
      release of mucin by guinea pig tracheal epithelial (GPTE) cells were measured
      using a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Each
      secretagogue significantly enhanced release of mucin, but the stimulatory effect
      of each was inhibited by pre-(+)co-incubation of the cells with the competitive
      inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMA), but not by
      NG-monomethyl-D-arginine (D-NMA), the inactive stereoisomer that does not inhibit
      nitric oxide synthase. Neither L-NMA nor D-NMA affected mucin secretion by
      themselves. The results suggest that each of these inflammation-associated
      mediators provokes airway epithelial mucin secretion via a mechanism involving
      intracellular production of nitric oxide (NO) as a critical signaling molecule.

PMID- 7576689
TI  - Functional desensitization of beta agonist responses in human lung mast cells.
AB  - The beta adrenergic agonist isoprenaline inhibited the IgE-triggered release of
      the preformed mediator histamine from human lung mast cells (HLMC) in a dose
      dependent fashion. After prolonged (> or = 4 h) preexposure of HLMC to
      isoprenaline, there was a subsequent diminution in the effectiveness of a second
      exposure of isoprenaline to inhibit the release of histamine from activated HLMC.
      This induced hyporesponsiveness to isoprenaline was both concentration and time
      dependent. Although maximal levels of desensitization were obtained after an
      initial prolonged (14-h) preincubation with a high (10(-5) M) concentration of
      isoprenaline, exposure of HLMC for a shorter (4-h) time period with a lower (3 x
      10(-7) M) concentration of isoprenaline was also effective at inducing a
      functional desensitization to isoprenaline. The inhibitory activity of the beta 2
      agonist fenoterol was attenuated after a prolonged (14-h) pretreatment step with
      isoprenaline (10(-5)M), whereas the inhibitory properties of other adenylate
      cyclase activators, prostaglandin E2 and forskolin, were not affected
      appreciably. Prolonged (12-h) exposure of HLMC to the beta agonists fenoterol,
      salbutamol, and terbutaline also induced hyporesponsive states of beta agonists,
      qualitatively similar to that obtained with isoprenaline. The beta receptor
      antagonist propranolol, if coincubated with isoprenaline during the prolonged
      pretreatment step, protected against the subsequent refractoriness of the HLMC to
      isoprenaline. The glucocorticoid dexamethasone failed to prevent the isoprenaline
      induced functional desensitization. In total, these results indicate that
      prolonged exposure of HLMC to beta agonists induces a state of selective
      hyporesponsiveness to agonists that act at beta adrenoreceptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576691
TI  - Adhesion of activated eosinophils to respiratory epithelial cells is enhanced by
      tumor necrosis factor-alpha and interleukin-1 beta.
AB  - Eosinophilic infiltration and damage to airway epithelium are characteristic
      features of asthma. To assess possible interactions between eosinophils and
      airway epithelium, Percoll-purified human peripheral blood eosinophils were
      evaluated for their ability to adhere to respiratory epithelial cell (REC)
      cultures. REC (an immortalized cell line, A549, and primary bronchial epithelial
      cells) were grown in 96-well tissue culture plates, treated with proinflammatory
      cytokines (TNF-alpha or IL-1 beta), and eosinophil adhesion to these tissues was
      determined. Cytokine treatment of the REC cultures significantly increased
      expression of intercellular adhesion molecule-1 (ICAM-1) (P < 0.01). Eosinophils
      demonstrated a variable baseline adhesion to untreated REC which was then
      significantly increased following activation with phorbol myristate acetate (PMA)
      (P < 0.01). Furthermore, treatment of REC monolayers with TNF-alpha or IL-1 beta
      significantly increased adhesion of PMA-stimulated eosinophils (P < 0.01). To
      delineate the adhesion proteins involved in the cell-cell interactions, assays
      were performed in the presence of specific blocking monoclonal antibodies to
      eosinophil CD18, CD11a, or CD11b, and REC ICAM-1 molecules. Blocking antibodies
      to ICAM-1 had no significant effect on levels of eosinophil adhesion. In
      contrast, antibodies to CD18, CD11a, and CD11b significantly decreased (P < 0.01)
      eosinophil adhesion, thus demonstrating pivotal roles for the CD11/CD18 (beta 2)
      integrins, but not necessarily for ICAM-1, in interactions between the REC and
      eosinophils. These data demonstrate that TNF-alpha and IL-1 beta increase
      eosinophil adhesion to human respiratory epithelial cell cultures by induction of
      ligands recognized by eosinophil beta 2 integrins.

PMID- 7576690
TI  - Activation of murine macrophages by silica particles in vitro is a process
      independent of silica-induced cell death.
AB  - We have tested the murine macrophagic cell line RAW 264.7 for its ability to
      undergo activation after exposure to silica particles in vitro. When exposed to
      silica under controlled conditions (each cell having access to about 10 silica
      particles), RAW 264.7 cells were able to phagocytose the particles.
      Concomitantly, there was a significant increase in tumor necrosis factor alpha
      (TNF alpha) mRNA accumulation and TNF alpha secretion. The level of TNF alpha
      production by RAW 264.7 cells increased up to 5-fold 48 h after phagocytosis of
      silica particles with very low cell toxicity. The phagocytic stimulus did not
      induce nitric oxide production. When cells were exposed to a higher number of
      silica particles, cell activation was attained at shorter times but a substantial
      number of cells were damaged at 48 h. Interferon gamma (IFN gamma) alone induced
      an increased production of TNF alpha in RAW 264.7 cells, not further augmented by
      a subsequent exposure to silica of the IFN gamma-treated cells. Other macrophage
      like cell lines as well as primary peritoneal macrophages were able to
      phagocytose silica particles but showed different abilities to produce and
      secrete TNF alpha once phagocytosis took place. Therefore, RAW 264.7 cells were
      chosen as a model for in vitro studies of the long-term response of macrophages
      to silica.

PMID- 7576692
TI  - Expression of calcitonin gene-related peptide by cultured rat alveolar type II
      cells.
AB  - Calcitonin gene-related peptide (CGRP) immunoreactivity is found in the airways
      in terminals of primary sensory afferents, in neuroendocrine cells, and in
      tracheal serous cells. This study shows that rat alveolar epithelial cells
      express immunoreactive CGRP also. Freshly isolated cells contained 34 +/- 23 fmol
      CGRP/10(7) cells (n = 4). Cultured type II cells secreted CGRP at a stable rate
      for 3 days after cell isolation, averaging 206 +/- 14 fmol CGRP/well/day (750,000
      cells plated/well with approximately 30% efficiency). The extracellular CGRP
      immunoreactivity eluted in the same fraction as rat CGRP-beta on high performance
      liquid chromatography. Secretion of CGRP from type II cells was reversibly
      blocked by monensin, an inhibitor of secretory protein transport. CGRP secretion
      was stimulated in a concentration-dependent fashion by phorbol myristate acetate,
      but it was not affected by forskolin, capsaicin, bradykinin, or nicotine. CGRP
      was not detected in culture media from alveolar macrophages or fibroblasts,
      potential contaminants of primary type II cell cultures. Calcitonin is expressed
      by neuroendocrine cells, but it was not detected in conditioned media from type
      II cell cultures. Thus, type II alveolar epithelial cells express and secrete
      CGRP. Secretion occurs constitutively and is regulated by a protein kinase C
      dependent pathway. Secretion is unaffected by increases in cyclic adenosine
      monophosphate or by treatments that induce release of CGRP from sensory afferent
      nerve terminals in the airways.

PMID- 7576693
TI  - Role of recruited neutrophils in interleukin-8 production in dog trachea after
      stimulation with Pseudomonas in vivo.
AB  - Cell-free supernatant of Pseudomonas aeruginosa (PA) recruits neutrophils into
      the airways indirectly by inducing the production of chemotactic factors,
      including interleukin-8 (IL-8). PA products stimulate IL-8 expression selectively
      in surface airway epithelium, gland ducts, serous cells, and recruited
      neutrophils. To examine the relative contribution of neutrophils in IL-8 release
      in the airway lumen, we studied the effect of inhibition of neutrophil
      recruitment on IL-8 concentration in tracheal fluid after introduction of PA
      supernatant into the dog trachea in vivo. Tracheal superfusion with PA
      supernatant caused neutrophil recruitment and increased the IL-8 concentration in
      the tracheal lumen; NPC 15669 inhibited both effects. To study whether migration
      of neutrophils into the airway lumen per se induces their expression of IL-8, we
      compared effects of local introduction of IL-8 and of PA supernatant into the
      trachea on IL-8 expression in neutrophils recruited into the trachea. PA
      supernatant, but not exogenous IL-8 alone, induced IL-8 mRNA expression in
      neutrophils recruited into the trachea. To determine what product(s) of PA
      stimulate IL-8 expression in neutrophils, we examined neutrophils isolated from
      peripheral blood. PA supernatant induced IL-8 production in neutrophils, an
      effect reproduced by PA lipopolysaccharide and inhibited by polymyxin B. These
      results suggest that neutrophils recruited into the airway lumen play a major
      role in local IL-8 production in airways in response to bacteria such as PA,
      depending on the presence of stimuli such as lipopolysaccharide.

PMID- 7576694
TI  - Transforming growth factor-beta regulates the expression of fibronectin and
      tenascin in BEAS 2B human bronchial epithelial cells.
AB  - We used monoclonal antibodies to study expression and extracellular matrix (ECM)
      incorporation of tenascin (Tn) and isoforms of fibronectin (Fn) in BEAS 2B
      immortalized human bronchial epithelial cells and the regulation of their
      synthesis by transforming growth factor (TGF)-beta 1 and -beta 2. In
      immunofluorescence microscopy, the control cells appeared negative for Tn.
      Extradomain A (EDA)-Fn was mainly seen in association with ECM fibers and, in a
      few cells, in an intracellular location. Immunoreactivity for oncofetal (onc)-Fn
      and extradomain B (EDB)-Fn was only seen in a few cells. In TGF-beta 1- and -beta
      2-treated cells, a greatly enhanced immunostaining for Tn and three isoforms of
      Fn was seen both as to the number of positive cells and to the amount of
      immunoreactive material around them. In Western blotting of the untreated cells,
      EDA-Fn and onc-Fn were detected in the cell-free ECM and in the culture medium,
      whereas EDB-Fn was not detectable. An enhanced secretion and deposition of both
      EDA-Fn and onc-Fn and also secretion of EDB-Fn was seen upon treatment with TGF
      beta s. In TGF-beta-treated cells, Tn was found exclusively in the ECM and not in
      the culture medium as shown by Western blotting of cell-free ECM and culture
      medium, respectively. Accentuation of tenascin staining in TGF-beta-treated cells
      was due to a greatly enhanced production of M(r) 280,000 and M(r) 190,000
      isoforms of Tn.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576695
TI  - Susceptibility to platelet-activating factor-induced airway hyperreactivity and
      hyperpermeability: interstrain variation and genetic control.
AB  - Platelet-activating factor (PAF) is a proinflammatory mediator known to elicit
      changes in airway reactivity and vascular permeability, and it may also have a
      role in the development and progression of acute respiratory distress syndrome
      and asthma. We have developed a mouse model to test the hypothesis that these
      traits were controlled by a single gene and were mechanistically related. We
      further hypothesized that there was a relationship between PAF-induced
      hyperreactivity and baseline reactivity to acetylcholine (ACh). Among eight
      inbred strains of mice that exhibited significant interstrain variation in ACh
      reactivity, intravenous PAF induced 16 to 278% increases in reactivity to ACh (25
      micrograms/kg). PAF also elicited 95 to 307% increases in lung permeability as
      measured by Evans blue extravasation. Both reactivity and permeability changes
      induced by PAF were blocked by a PAF receptor antagonist (L-659,989). Strain
      distribution patterns for baseline reactivity to ACh and PAF-induced
      hyperreactivity and lung permeability were not significantly concordant, and
      suggest that the variables were not interdependent. Progeny derived from AKR/J
      (PAF hyperresponsive) and C3H/HeJ (PAF hyporesponsive) mice were characterized
      for their PAF responsiveness as determined by PAF-induced hyperreactivity and
      hyperpermeability. The ratios of hyperresponsive and hyporesponsive phenotypes in
      outcross progeny were compared to those predicted for Mendelian inheritance and
      assessed for relatedness by chi 2 and cosegregation analyses. Results suggested
      that PAF-induced hyperreactivity was controlled by a single gene, but PAF-induced
      hyperpermeability was controlled by a more complicated interaction of
      factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576696
TI  - Hemoglobin provides protection against lethal endotoxemia in rats: the role of
      heme oxygenase-1.
AB  - Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme
      to bilirubin. HO-1 is highly induced by heme, its major substrate, and nonheme
      products, including metal ions and hormones. Interest in HO-1 has been stimulated
      recently by observations that HO-1 is also highly induced in response to
      oxidative stress in vitro. The physiologic significance of HO-1 induction
      following oxidant injury in vivo, however, is poorly understood. In a rat model
      of lipopolysaccharide endotoxin (LPS)-induced lung injury and sepsis, we
      demonstrate that the lung responds to LPS by expressing high levels of HO-1 mRNA
      and enzyme activity. We hypothesize that this HO-1 induction could play a
      critical role in the lung's defense against LPS. Pretreatment of rats with
      hemoglobin, a potent inducer of HO-1, resulted in HO-1 induction and more
      importantly provided complete protection against subsequent lethal endotoxemia
      (100% survival). Tin protoporphyrin, a competitive inhibitor of HO, blocked this
      protective effect of hemoglobin and rendered the rats more susceptible to a
      lethal dose of LPS. Taken together, these data strongly implicate HO-1 in playing
      an important role in the defense against endotoxic shock, with potential
      therapeutic implications.

PMID- 7576697
TI  - Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion
      molecule-1 in pulmonary epithelial cells infected with respiratory syncytial
      virus.
AB  - The mechanisms of virus-induced enhancement of intercellular adhesion molecule-1
      (ICAM-1) expression in epithelial cells are unknown. In the present study, the
      effect of respiratory syncytial virus (RSV) infection on the expression of ICAM-1
      in human pulmonary type II-like epithelial (A549) cells was evaluated.
      Conditioned RSV media (cRSV) produced from growth of RSV in A549 cells induced a
      significant increase in the expression of ICAM-1. Treatment of the cells with
      noninfectious cRSV prepared by ultraviolet (UV) irradiation (UV-cRSV) or
      ribavirin treatment resulted in the expression of ICAM-1 to a similar extent as
      infectious cRSV. These results suggested that RSV induces the synthesis of a
      soluble mediator(s) that regulates the expression of ICAM-1. Cytokine analysis by
      immunoassay and polymerase chain reaction showed that RSV induces the synthesis
      of interleukin (IL)-1 alpha and -beta, and tumor necrosis factor alpha (TNF
      alpha). Preincubation of UV-cRSV with soluble IL-1 receptor (sIL-1r) almost
      completely blocked the enhancement of ICAM-1 expression. Furthermore,
      simultaneous incubation of infectious purified RSV with sIL-1r resulted in a
      significant reduction in enhancement of ICAM-1 expression. Preincubation with
      neutralizing antibodies to IL-1 alpha and -beta, and TNF-alpha showed that the
      predominant ICAM-1 enhancing soluble mediator in UV-cRSV was IL-1 alpha. These
      experiments provide direct evidence for an autocrine mechanism of enhanced ICAM-1
      expression in RSV-infected epithelial cells that is mediated primarily by IL-1
      alpha. Pulmonary epithelial cells may play an important immunoregulatory role in
      the microenvironment of the lower respiratory tract infected with RSV.

PMID- 7576698
TI  - Infection, apoptosis, and killing of mature human eosinophils by human
      immunodeficiency virus-1.
AB  - Although human eosinophils express low concentrations of CD4, the capacity of
      mature, non-replicating eosinophils to be infected with human immunodeficiency
      virus-1 (HIV-1) has not been established. Using peripheral blood eosinophils
      isolated free of contaminating lymphocytes and mononuclear leukocytes, we
      evaluated eosinophil infection with HIV-1. Eosinophils could be infected with
      strains of HIV-1 as evidenced by HIV-induced cytolytic effects, progressive
      release of p24 antigen in cultures of infected eosinophils, recovery of HIV from
      infected eosinophils by co-cultivation, and detection of HIV-1 gag viral DNA from
      infected eosinophils by polymerase chain reaction (PCR) amplification. Greater
      p24 antigen release from infected eosinophils was elicited by the phorbol ester,
      PMA; and eosinophil killing by HIV-1 was enhanced by the cytokine GM-CSF. By
      light and electron microscopy, HIV-infected eosinophils demonstrated apoptosis
      and necrosis. Apoptotic subdiploid nuclear staining was detected by flow
      cytometric analyses of propidium iodide-stained nuclei from HIV-infected
      eosinophils, and DNA isolated from HIV-infected eosinophils showed both
      nucleosomal fragmentation and diffuse degradation. Thus, mature eosinophils, non
      replicating terminally differentiated leukocytes, can be infected with HIV-1. HIV
      1 expression in eosinophils is promoted by increased granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and can cause eosinophils to undergo death due
      to apoptosis and necrosis.

PMID- 7576699
TI  - Effect of human lung allograft alveolar macrophages on IgG production:
      immunoregulatory role of interleukin-10, transforming growth factor-beta, and
      interleukin-6.
AB  - Alveolar macrophages (AM) are crucial to initiating and maintaining local immune
      responses. The increased susceptibility to pulmonary infections in lung allograft
      recipients may be due to impaired AM function resulting in diminished cellular
      and humoral immunity. We have previously reported that control AM were potent
      stimulators of IgG production from allogeneic peripheral blood mononuclear cells
      (PBM) in a manner that was dependent on gamma-interferon (gamma IFN). The ability
      of allograft AM to induce IgG production is unknown. The purpose of the current
      study was to compare the ability of allograft and control AM to induce IgG
      production from allogeneic PBM. In contrast to control AM which induced a dose
      dependent stimulation of IgG production from allogeneic PBM, allograft AM were
      highly suppressive of IgG production. The inhibition was not due to a lack of
      allograft AM stimulation of gamma IFN production from responding lymphocytes.
      Supernatants from allograft AM were highly suppressive of control AM-induced IgG
      production. Allograft AM produced greater quantities of interleukin (IL-10) than
      control AM while transforming growth factor-beta (TGF-beta) production from these
      cells was comparable. Blocking antibodies to IL-10 and TGF-beta reversed the
      inhibition of IgG production to 63% and 60% of control, respectively. In
      addition, the production of interleukin 6 (IL-6), a macrophage-derived cytokine
      crucial to the stimulation of IgG synthesis, was deficient in the allograft AM.
      Addition of IL-6 to allograft AM and allogeneic PBM co-cultures restored IgG
      synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576700
TI  - Hyperoxia alone causes changes in lung proteoglycans and hyaluronan in neonatal
      rat pups.
AB  - Specific changes in composition and content of lung extracellular matrix (ECM)
      proteoglycans (PGs) and hyaluronan (HA) have been observed during the acute
      response to damage in several forms of injury including infant respiratory
      distress syndrome (IRDS). These ECM components are thought to modulate the
      healing response. Hyperoxia, a contributing factor to IRDS, is known to damage
      both adult and developing lung, however, the extent and pattern of impairment
      depends on lung maturity. We hypothesized that exposing neonatal rats to
      hyperoxia alone might result in changes in lung HA, as well as in age-specific
      changes in lung PGs, similar to those shown to occur in IRDS. In control rats,
      lung HA decreased over the first 10 days of life, whereas rats exposed to
      hyperoxia exhibited a time-dependent, time-limited increase in both lung HA and
      lung wet weight. Histochemistry showed the HA in hyperoxia-exposed lungs to be
      accumulated in perivascular cuffs of medium sized arteries, and in the alveolar
      walls. Rats were then exposed to normoxia or hyperoxia for 7 days beginning at
      either 3 days of life (neonatal) or 21 days (adolescent), and lung tissue was
      cultured in the presence of [35S]-sulfate to label newly synthesized PGs.
      Proteoglycans were extracted, and analyzed by isopycnic CsCl gradient
      centrifugation, sequential enzymatic deglycosylation, size chromatography, and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). When
      controlled for total protein extracted, 63% more label was incorporated into
      large molecular weight material in the tissue exposed to hyperoxia, with a 95%
      increase in incorporation in the most dense fraction, D1. [35S]-Sulfate
      incorporation into chondroitin and dermatan sulfate in hyperoxic tissue
      specifically increased 116% (242% in the D1 fraction), while incorporation into
      heparan sulfate remained essentially unchanged. There was a nearly fivefold
      increase in [35S]-sulfate incorporation into chondroitin sulfate chains in the D1
      fraction. When the D1 fractions of extracts of treated and control rat lungs were
      compared on SDS-PAGE, a large chondroitin sulfate proteoglycan (CSPG; core
      protein of 195 kDa) was upregulated in the D1 fraction from hyperoxic tissue of
      neonatal rats, but was not detected in the lungs of adolescent animals exposed to
      hyperoxia. This CSPG and four additional large CSPGs were noted to be upregulated
      on western blotting by a polyclonal antibody directed against the G1 domain of
      the aggrecan protein core. We conclude that hyperoxia alone causes an increase in
      lung HA and lung water, and speculate that this contributes significantly to the
      clinical syndrome of IRDS. In addition, several large CSPGs are upregulated by
      hyperoxic exposure in a developmentally specific manner. We speculate that this
      increase in CSPGs may interfere with the normal developmental sequence of events,
      contributing to hypoalveolarization.

PMID- 7576701
TI  - Eosinophils as a potential source of platelet-derived growth factor B-chain (PDGF
      B) in nasal polyposis and bronchial asthma.
AB  - Tissue remodeling in bronchial tissues from asthmatics as well as in nasal polyp
      (NP) tissues includes sub-basement membrane deposition of collagen, stromal
      deposition of extracellular matrix protein, and hypertrophy/hyperplasia of airway
      smooth muscle cells, which are relevant to the cellular and molecular events
      induced by platelet-derived growth factor (PDGF). Therefore, we investigated the
      localization of mRNA and protein of PDGF-B chain (PDGF-B) in NP tissues and
      bronchial tissues from mild and severe asthmatics by in situ hybridization and
      immunohistochemistry, respectively. Cells expressing PDGF-B mRNA were found in
      all nine NP tissues and in bronchial tissues from 2 of 6 normal subjects, 2 of 5
      mild asthmatics, and all of 6 severe asthmatics examined. The vast majority of
      cells expressing PDGF-B mRNA were eosinophils in NP (99.7 +/- 0.2%, mean +/- SD)
      and asthmatic bronchial tissues (75.0 and 77.8% in mild asthma, and 92.7 +/- 8.1%
      in severe asthma), but no cells expressing PDGF-B mRNA were eosinophils in normal
      bronchial tissues. The number of cells expressing the gene in severe asthma
      tissues (122.3 +/- 32.2/mm2) was similar to that in NP tissues (152.8 +/-
      73.9/mm2) and greater than that in mild asthma tissues (4.7 +/- 7.6/mm2, P <
      0.01), which was not significantly greater than that in normal bronchial tissues
      (3.4 +/- 5.2/mm2). Furthermore, we detected immunolocalization of PDGF-B in NP
      tissues and in asthmatic bronchial tissues. The eosinophils purified from
      peripheral blood were demonstrated to express PDGF-B gene transcript and
      immunoreactivity after stimulation with A23187.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576702
TI  - Distinct expression patterns of CD44 isoforms during human lung development and
      in pulmonary fibrosis.
AB  - The transmembrane glycoprotein CD44 represents a family of molecules, all encoded
      by one gene. The variability of the isoforms is generated by alternative splicing
      of the nuclear RNA. Apart from the abundant standard form (CD44s), the variant
      isoforms (CD44v) are mostly restricted to epithelia. The present study
      demonstrates the expression of CD44s and CD44v isoforms in embryonic and fetal
      lungs and in normal and pathologically altered (pulmonary fibrosis after radio-
      or chemotherapy) human adult pulmonary tissues. Using double immunofluorescence
      and avidin biotin complex (ABC) techniques on paraffin sections, presence of
      CD44s and CD44v isoforms (CD44v4, CD44v6, CD44v9) has been analyzed. In normal
      lung tissue, CD44s is present at the cell surface of alveolar macrophages, in
      some interstitial cells and in epithelial cells. It is also present in epithelial
      and non-epithelial cells during lung development. CD44v isoforms containing exon
      v6 and v9 encoded epitopes are selectively detectable in normal epithelial cells
      with a strong basolateral distribution pattern in the entire population of type
      II pneumocytes and in basal cells of the bronchial epithelium. During development
      exon v9 encoded isoforms appear at the pseudoglandular stage, whereas CD44v6 has
      only been found at the saccular stage. Examination of 12 fibrotic lung samples
      has revealed major alterations in the CD44 expression in comparison to normal
      lung tissue. These changes include cytoplasmic deposits of CD44s in alveolar
      epithelial cells and reduced expression of the CD44v6 and CD44v9 isoforms in
      alveolar epithelial and bronchial epithelial cells. The results suggest that
      CD44v isoforms may be utilized by type II pneumocytes in epithelial-mesenchymal
      interactions and in the maintenance of the pulmonary histoarchitecture.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576703
TI  - CFTR-mediated chloride permeability is regulated by type III phosphodiesterases
      in airway epithelial cells.
AB  - Chloride channel activity of cystic fibrosis transmembrane conductance regulator
      (CFTR) requires activation of protein kinase A (PKA) by 3'-5'-cyclic adenosine
      monophosphate (cAMP). The level of cAMP is controlled by the balance between cAMP
      synthesis and hydrolysis by adenylate cyclase and phosphodiesterases (PDEs),
      respectively. CFTR channel activity appears to be most sensitive to the activity
      of type III cyclic nucleotide PDEs in Calu-3 and 16HBE cells, both derived from
      airway epithelium and expressing wild-type CFTR. Type III PDEs can be identified
      by their sensitivity to specific inhibitors such as milrinone and amrinone. In
      Calu-3 cells, specific inhibition of type III PDEs increased chloride efflux up
      to 13.7-fold, whereas neither rolipram nor Ro20-1724 (type IV PDE inhibitors) nor
      3-isobutyl-1-methylxanthine (IBMX, a nonspecific PDE inhibitor) elicited
      significant increases. None of these compounds had an appreciable effect on total
      cellular cAMP levels, yet the effects of milrinone and amrinone on chloride
      efflux were blocked by treatment of cells with Rp-cAMPS, a cAMP analog that
      inhibits PKA at the site of cAMP binding. Similarly, H-8, an inhibitor of PKA,
      reduced milrinone-stimulated chloride efflux, indicating that efflux is mediated
      through the cAMP/PKA pathway. Whole-cell patch clamp analysis revealed that
      milrinone generated chloride conductances with properties consistent with those
      of CFTR. Milrinone elicited chloride currents in a dose-dependent manner and
      induced CFTR activity in the absence of adenylate cyclase agonists. These data
      suggest that type III PDEs are specifically involved in CFTR activation in airway
      epithelial cells and that PDE regulation of CFTR may involve subcellular
      compartments of cAMP.

PMID- 7576704
TI  - Human lung mast cell IL-5 gene and protein expression: temporal analysis of
      upregulation following IgE-mediated activation.
AB  - The late-phase of allergic asthma is characterized by infiltration of the airway
      with eosinophils within 6 h of mast cell activation. Pro-eosinophilic/pro
      allergic (TH2) cytokines, originally described as T-lymphocyte products, have
      recently been ascribed to mast cells as well. To date, however, it is unknown if
      TH2 cytokine gene expression by the human mast cells is subject to receptor
      mediated regulation analogous to that of T-cells, and if messenger RNA (mRNA)
      expression results in protein secretion occurring in a temporal context
      consistent with the late-phase response. We examined interleukin-4 (IL-4), IL-5,
      and IL-6 mRNA expression induced by anti-IgE activation of human lung explants as
      assessed using reverse transcription/polymerase chain reaction (RT-PCR). Anti-IgE
      stimulation resulted in rapid and sustained upregulation of IL-5 message, but did
      not have analogous effects on IL-4 or IL-6. Using quantitative-competitive PCR,
      we demonstrated that 100 ng of total cellular RNA from human lung contained 1 fg
      of IL-5 mRNA; this increased to 100 fg 4 h after anti-IgE activation. The source
      of the anti-IgE-enhanced IL-5 mRNA is likely the mast cell itself, as anti-CD3
      activation of lung led to a dissimilar array of cytokine expression. In addition,
      human lung mast cells purified to near homogeneity expressed IL-5 mRNA after
      activation, as shown by both RT-PCR and in situ hybridization. In both lung
      fragments and purified human lung mast cells, the modulation of IL-5 mRNA
      expression preceded the secretion of IL-5 protein, detected as early as 4 h after
      activation. Neither isolated purified mast cells nor purified peripheral blood T
      cells could be induced to secrete detectable amounts of IL-5 protein when
      activated only with antibodies against IgE or CD3-T cell receptor complex,
      respectively. However, mast cells (n = 4) and T cells (n = 6) cultured at
      comparable concentrations (4 x 10(6)/ml) activated through their respective
      antigen receptors in the presence of phorbol ester yielded comparable IL-5
      production (253 +/- 126 pg/ml versus 183 +/- 75 pg/ml, mean +/- SE). We conclude
      that mast cells are analogous to T cells in the requirement of co-stimuli for the
      production of IL-5 protein. Moreover, the rapid kinetics of IgE-mediated IL-5
      transcription and protein elaboration are consistent with a primary role for mast
      cell activation directly leading to late-phase airway eosinophilia.

PMID- 7576705
TI  - Pulmonary endothelial nitric oxide synthase gene expression is decreased in a rat
      model of congenital diaphragmatic hernia.
AB  - Nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS) is
      critically involved in the cardiopulmonary transition from fetal to neonatal
      life. In congenital diaphragmatic hernia (CDH) this transition often does not
      occur normally, resulting in persistent pulmonary hypertension of the newborn
      (PPHN). We sought to determine if pulmonary NOS expression is altered in a rat
      model of CDH induced by maternal ingestion of the herbicide 2,4-dichlorophenyl-p
      nitrophenyl ether (Nitrofen) on day 9 of gestation (term = 22 days). Sixty-three
      percent of Nitrofen-exposed fetuses developed CDH. Endothelial NOS (eNOS) and
      neuronal NOS (nNOS) protein expression were assessed in ipsilateral CDH lungs and
      in control lungs (Nitrofen-treated, no hernia) at 20 d gestation using immunoblot
      analyses. eNOS and nNOS have been immunohistochemically localized to rat
      pulmonary endothelium and bronchiolar epithelium, respectively, and we have
      previously demonstrated that their expression normally increases during late
      gestation to be maximal near term. eNOS protein expression was decreased in CDH
      versus control lung (58 +/- 6 versus 100 +/- 6% of control, n = 5). In contrast,
      nNOS protein abundance was similar. Factor VIII-associated antigen expression was
      comparable in CDH and control lung, indicating that the change in eNOS is not
      related to differences in endothelial cell density. eNOS mRNA abundance was
      evaluated in semiquantitative reverse transcription-polymerase chain reaction
      assays. Paralleling the decline in eNOS protein expression, eNOS mRNA was
      decreased in CDH versus control lung (22 +/- 8 versus 100 +/- 31% of control, n =
      4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576706
TI  - Increased expression of heat shock protein 70 on airway cells in asthma and
      chronic bronchitis.
AB  - Heat shock proteins (HSPs) appear to be involved in inflammation. Because asthma
      is an inflammatory disease, HSPs may be expressed. We studied the expression of
      HSP-70 by immunohistochemistry using the alkaline-phosphatase anti-alkaline
      phosphatase technique on epithelial cells and alveolar macrophages (AMs) from 19
      patients with asthma, eight patients with chronic bronchitis (CB), and 13 control
      subjects and in bronchial biopsies from 15 asthmatics, 15 CB patients, and nine
      control subjects. The specificity of the antibody was confirmed by Western
      blotting on heated AM. The specificity of the immunostaining was confirmed by
      inhibition experiments. The expression of HSPs in the asthmatics in comparison
      with the CB patients and control subjects was significantly increased on
      epithelial cells (P < 0.002 and P < 0.007, respectively) and AMs (P < 0.0004 and
      P < 0.0002, respectively) and was significantly correlated with the severity of
      asthma (P < 0.005 for AMs) and the percentage of eosinophils in bronchoalveolar
      lavage fluid (P < 0.004). In biopsies from the asthmatics but not from the CB
      patients or control subjects, a positive staining for HSP-70 was observed on
      epithelium, mononuclear cells, and basement membrane and was correlated with the
      severity of asthma (P < 0.0005, P < 0.002, and P < 0.007, respectively). This
      study demonstrates that bronchial inflammation in asthma but not in CB may be
      linked to the production of HSPs.

PMID- 7576707
TI  - Effects of nonselective and isozyme selective cyclic nucleotide phosphodiesterase
      inhibitors on antigen-induced cytokine gene expression in peripheral blood
      mononuclear cells.
AB  - Cyclic nucleotide phosphodiesterase (PDE) enzymes may participate in regulation
      of the inflammatory response through their effects on second messengers. In the
      present study, we have investigated the role of nonselective and isozyme
      selective PDE inhibitors in altering the antigen-driven cytokine gene expression
      of peripheral blood mononuclear cells (PBMCs) from atopic individuals. Ragweed
      and tetanus toxoid were used as model antigens. The nonselective PDE inhibitor, 3
      isobutyl-1-methylxanthine (IBMX), and the selective PDE4 inhibitor, rolipram,
      markedly suppressed interleukin-5 (IL-5) and interferon gamma (IFN gamma) gene
      expression in both antigen-driven systems. Gene expression for IL-4 was
      unaffected by these agents in the ragweed-driven system. Message for IL-4 could
      not be detected in the tetanus toxoid-driven system, despite the use of a
      quantitative, competitive reverse transcription-polymerase chain reaction (RT
      PCR) assay sensitive to less than 10 fg of target template. The PDE3 inhibitor,
      siguazodan, was ineffective in downregulating gene expression for the
      proinflammatory cytokines assayed; when used in combination with the PDE4
      inhibitor, the PDE3 inhibitor provided no increase in efficacy over that seen
      with the PDE4 inhibitor alone. Gene expression for the A and B isoforms of the
      PDE4 in PBMCs was unaffected by antigen stimulation or treatment with the PDE4
      inhibitor; however, differences in expression of these two isoforms were apparent
      when a variety of immune cell lines were studied. These data support the
      hypothesis that the primary anti-inflammatory target for PDE inhibition in PBMCs
      is the PDE4. Furthermore, the expression of various isoforms of this enzyme may
      differ between immune cell types. Finally, PDE4 isoform expression in PBMCs is
      independent of treatment with an isozyme selective inhibitor.

PMID- 7576708
TI  - Accelerated binding of secretory leukoprotease inhibitor to human leukocyte
      elastase mediated by single-stranded sites in DNA from tracheobronchial mucus.
AB  - We have found that preparations of DNA isolated from purulent sputum possess a
      novel activity which accelerates and stabilizes the binding of human leukocyte
      elastase to secretory leukoprotease inhibitor, a major endogenous antielastase in
      the respiratory tract. DNA in sputum is derived from the nuclear debris of
      disintegrated inflammatory leukocytes, and can attain concentrations ranging from
      10(2) to 10(4) micrograms/ml, depending on the severity of pulmonary infection
      and inflammation. In the presence of 23 micrograms/ml DNA, a concentration lower
      than those found in most purulent sputa, the rate constant for association of
      secretory leukoprotease inhibitor with elastase is increased to 1.1 x 10(8) M-1s
      1, 44-fold greater than that in the absence of DNA. The equilibrium dissociation
      constant for the enzyme-inhibitor complex drops to 0.7 pM, two orders of
      magnitude lower than that in the absence of DNA. The accelerating effect of DNA
      is further increased by thermal denaturation or by modification with exonuclease
      III, while it is significantly reduced by digestion with S1 nuclease or by
      binding of Escherichia coli single-stranded DNA binding protein. The results from
      these experiments indicate that the structural elements in sputum DNA that are
      responsible for the accelerating effect have the characteristics of single
      stranded sites. Similar kinetic effects on elastase inhibition were also observed
      with human placental DNA and genomic DNAs from a variety of other species. These
      findings suggest that DNA in pulmonary secretions may participate in antielastase
      defense by promoting the binding of secretory leukoprotease inhibitor to
      leukocyte elastase. The results may have important implications for use of
      nuclease preparations in mucolytic therapy for cystic fibrosis.

PMID- 7576709
TI  - Surfactant incorporation markedly alters mechanical properties of a fibrin clot.
AB  - Intra-alveolar clot formation is a common finding in acute and chronic
      inflammatory lung diseases. Incorporation of lipophilic surfactant components
      into a growing fibrin clot has recently been reported (Am. J. Respir. Cell Mol.
      Biol. 1993; 9:213-220). In the present study, we investigated the influence of
      such surfactant incorporation on the elastic properties and water permeability of
      the fibrin polymer. Thrombelastography and compaction experiments were employed
      for assessment of the elastic properties, and the permeability characteristics of
      the clot material were addressed in fibrin-packed columns. Two calf lung
      surfactant extracts (CLSE and Alveofact), Curosurf, and a synthetic phospholipid
      mixture (dipalmitoylphosphatidylcholine, phosphatidylglycerol, and palmitic acid
      at a ratio of 68.5:22.5:9 [wt/wt]) were used. The presence of surfactant did not
      affect the cleavage of fibrinopeptide A upon incubation of fibrinogen with
      thrombin (enzyme-linked immunosorbent assay technique). Similarly, kinetics and
      extent of factor XIII-induced covalent crosslinkage of the fibrin network
      remained unchanged in the presence of surfactant (sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and D-Dimer quantification upon subsequent
      clot lysis). All surfactants, however, dose-dependently decreased the elastic
      modulus of the arising fibrin polymer. The maximal amplitude in
      thrombelastography was reduced, and the recovery of fluid after centrifugation of
      the fibrin clot increased. Fibrin clots embedding natural surfactant material
      displayed reduced permeability for saline as compared with control fibrin
      polymers. Subsequent washout of lipids from these clots with Triton X-100
      resulted in increased hydraulic conductivity. This was accompanied by an increase
      in pore size, suggesting altered architecture of the fibrin matrix generated in
      the presence of surfactant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576710
TI  - Effect of neutrophil mediators on epithelial permeability.
AB  - Inflammatory lung disease is associated with increased epithelial permeability,
      but it is unclear how inflammatory cells alter epithelial permeability.
      Neutrophils have azurophilic granules containing elastase, cathepsin G, and
      defensins which are released at sites of inflammation. Experiments using whole
      animals and cultured cells suggest that neutrophil elastase contributes to
      increased epithelial permeability. Using Madin-Darby canine kidney epithelial
      (MDCK) monolayers, a well-described epithelial model, we asked whether neutrophil
      elastase directly affects epithelial permeability independent of cell death or
      cell detachment from the substratum. We measured permeability using 3H-mannitol.
      We found that neutrophil elastase increased epithelial permeability in a time-
      and concentration-dependent fashion. Increased permeability required prolonged (>
      or = 6 h) exposure to elastase, but was not associated with cytolytic injury or
      cell detachment. These findings are potentially relevant to the lung because we
      found a similar time- and concentration-dependent effect when we added elastase
      to cultured human bronchial epithelial cells. In MDCK cells, permeability
      increased without alterations in cell actin at the light microscopic level.
      Interestingly, elastase-induced permeability was both prevented and reversed by
      serum, but not by serum albumin. Complete reversal occurred if serum was added up
      to 16 h after adding elastase. Proteolytic activity is important in HNE-induced
      epithelial permeability because soy bean trypsin inhibitor completely blocks the
      effect and alpha 1 proteinase inhibitor (alpha 1 PI) partially blocks the effect.
      Charge interactions also appear to be important because the polyanions heparin
      and sulfated dextran completely blocked increased permeability following elastase
      but only partially blocked elastolytic activity in isotonic solutions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576711
TI  - The effect of conditioned medium from cultured human bronchial epithelial cells
      on eosinophil and neutrophil chemotaxis and adherence in vitro.
AB  - Several studies have demonstrated that bronchial epithelial cells are capable of
      synthesizing proinflammatory cytokines that may influence eosinophil and
      neutrophil activity. We have cultured human bronchial epithelial cells to
      confluence, as explant cultures, and investigated the effect of conditioned
      medium from these cells on (1) the chemotaxis of eosinophils and neutrophils and
      (2) the adherence of these cells to cultured human endothelial cells. Analysis of
      cytokines, namely interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8), tumor
      necrosis factor alpha (TNF alpha), granulocyte/macrophage colony-stimulating
      factor (GM-CSF), and RANTES, which are thought to be involved in these processes,
      demonstrated that all these cytokines were synthesized and released
      constitutively from the bronchial epithelial cell cultures. Conditioned medium
      obtained after 24 h of incubation significantly increased the chemotaxis of
      eosinophils and neutrophils, from median values of 4.0 cells/per high power field
      (hpf) (range, 3.0 to 7.0) and 17 cells/hpf (range, 13.0 to 25.0), respectively,
      for medium 199, to median values of 11.0 cells/hpf (range, 9 to 12; P = 0.005)
      and 30 cells/hpf (range, 19 to 33; p = 0.01). Whereas anti-GM-CSF and anti-IL-8
      neutralizing monoclonal antibodies significantly attenuated the conditioned
      medium-induced chemotaxis of eosinophils and neutrophils, anti-RANTES
      neutralizing antibody significantly attenuated the chemotaxis of only
      eosinophils. Conditioned medium also significantly increased the percentage of
      eosinophils and neutrophils adhering to endothelial cells in a dose-dependent
      manner. Both anti-human TNF alpha and anti-human IL-1 beta neutralizing
      antibodies significantly attenuated the conditioned medium-induced adherence of
      eosinophils and neutrophils to the endothelial cells and were found to have an
      additive effect when studied together. Similarly, treatment of endothelial cells
      with either anti-ICAM-1 or anti-E-selectin, for 1 h before co-culture with
      eosinophils and neutrophils, significantly attenuated the conditioned medium
      induced adherence of both eosinophils and neutrophils to endothelial cells.
      Treatment of endothelial cells with anti-VCAM-1 attenuated the adherence of
      eosinophils but not neutrophils. These results suggest that human bronchial
      epithelial cells, through their ability to generate proinflammatory mediators,
      are likely to play a role in the pathogenesis of airway disease by influencing
      chemotaxis and adherence of eosinophils and neutrophils.

PMID- 7576712
TI  - Early identification of interleukin-16 (lymphocyte chemoattractant factor) and
      macrophage inflammatory protein 1 alpha (MIP1 alpha) in bronchoalveolar lavage
      fluid of antigen-challenged asthmatics.
AB  - Accumulation of CD4+ interleukin (IL)-2R+ lymphocytes in the airways of
      asthmatics is generally attributed to the presence of chemoattractant cytokines.
      The precise mechanism for the initiation of the earliest CD4+ lymphocyte
      infiltration and activation is unknown. In this study, we describe for the first
      time the presence of lymphocyte chemoattractant activity in the bronchoalveolar
      lavage (BAL) fluid obtained from asthmatics 6 h after antigen challenge. The
      majority of the chemoattractant activity at this early time point is represented
      by IL-16 (lymphocyte chemoattractant factor), a CD4+ cell-specific
      chemoattractant and growth factor. In addition to IL-16, macrophage inflammatory
      protein 1 alpha (MIP1 alpha) chemotactic bioactivity was detected in significant
      levels. While IL-16, MIP1 alpha, and IL-8 were all identified by enzyme-linked
      immunosorbent assay, the great majority of the lymphocyte chemoattractant
      activity in the BAL fluid after antigen challenge is attributable to IL-16 and
      MIP1 alpha. There were no detectable levels of IL-16 nor MIP1 alpha in BAL fluid
      of antigen-challenged normal subjects nor atopic nonasthmatics nor in saline
      challenged lobes from the asthmatics. The identification of multiple lymphocyte
      chemoattractants early after antigen challenge suggests a complex cellular, as
      well as chemoattractant cytokine, profile in initiating the CD4+ T cell-mediated
      inflammatory process that is specific for the atopic asthmatic phenotype.

PMID- 7576713
TI  - Analysis of respiratory mucus glycoproteins in asthma: a detailed study from a
      patient who died in status asthmaticus.
AB  - Airway mucus from asthmatics is often unusually solid. The death of a patient in
      status asthmaticus allowed the collection of 28 g of abnormal airway mucus at
      autopsy. Its chemical and physical properties were studied to reveal differences
      from more normal airway mucus. The gel plug taken from the airways could be
      dispersed in 6 M guanidinium chloride, but it took > 1 wk and 700 ml of
      extractant to disperse 3 g of exudate completely. In contrast, treatment with 10
      mM dithiothreitol, which reduces disulfide bonds, dispersed the gel within
      seconds. Mucins accounted for 25% of the non-dialyzable material in the gel,
      while DNA constituted < 1% and proteoglycans could not be detected. The mucins
      were similar in architecture and general composition to other respiratory mucins
      and were present at a high concentration (approximately 40 mg/ml). The majority
      of mucins were of extreme size (mean M(r) 30-40 x 10(6)) and slow to dissolve,
      but sequential extraction experiments on the gel exudate demonstrated a
      proportion of mucins (15%), the most readily extracted, which had a higher
      density, 1.45-1.55 g/ml, a lower M(r) (11.5 x 10(6)) and were markedly more
      acidic than the bulk of the mucins. Both major and minor mucin populations were
      extremely heterogeneous in mass distribution. Electron microscopy of the major
      mucin species demonstrated extensive networks of molecules many microns in
      length. The major mucin species was distinctly less acidic than mucins previously
      described from either normal or diseased airways. Amino acid analysis of
      fractions across the charge distribution suggested the presence of at least two
      different mucin proteins occurring as distinct glycoforms.

PMID- 7576714
TI  - T cell proliferation restricted by HLA class II molecules in patients with hen's
      egg allergy.
AB  - We investigated the synergistic effect of anti-HLA class II monoclonal antibodies
      on proliferative responses to ovalbumin (OA) of T cell line (TCL) cells from five
      hen's-egg-sensitive patients. Among the five patients, the proliferation of the
      TCL cells from two patients with AD who have a low immune reaction was restored
      by the anti-HLA-DQ monoclonal antibodies, and the proliferation of the TCL cells
      from the other three patients was inhibited by the anti-HLA-DP monoclonal
      antibodies. These results suggest that a component of the T cell repertoire
      reactive with OA in hen's-egg-sensitive patients may be restricted by HLA-DP
      molecules. Furthermore, in hen's-egg-sensitive patients with AD who have a low
      immune reaction, low responsiveness may be regulated by HLA-DQ molecules.

PMID- 7576715
TI  - Fluorescent detection of microsatellite polymorphisms: properdin deficiency
      linked to PFC microsatellite.
AB  - Microsatellite polymorphisms are widely used to map the genes responsible for
      inherited disorders. The most commonly used detection is based on radioactive
      labelling and autoradiography. We now present the successful detection of
      fluorescence-labelled allelic fragments on an automated DNA sequencer. This
      allows for safer and quicker detection as well as a potential for more efficient
      processing of the data, e.g. for linkage analysis. The system was tested in the
      mapping of properdin deficiency, an X-linked condition with increased risk for a
      severe infection in the affected.

PMID- 7576716
TI  - Complement C7 M/N allotyping in infectious diseases.
AB  - The allotypes of the C7 M/N polymorphism are determined by ELISA by comparing the
      reaction pattern of the allospecific monoclonal antibody WU 4-15 with that of
      polyclonal anti-C7 IgG. In order to find disease associations of the two alleles
      C7*M and C7*N we tested 528 hospitalised patients, most of them suffering from
      infectious diseases. No significant association of either of the two C7 M/N
      alleles to a particular disease was found, in particular refuting the hypothesis
      that Lyme borreliosis may be more frequent in homozygous carriers of the
      hypomorphic allele C7*N.

PMID- 7576718
TI  - Length polymorphism of the human complement component C4 gene is due to an
      ancient retroviral integration.
AB  - The fourth component of the complement system, C4, is encoded by two highly
      homologous MHC-linked genes expressing the two isotypes C4A and C4B. A gene size
      polymorphism (either 22.5 or 16 kb) has been described which depends on the
      presence or absence of a 6.5-kb insertion in intron 9 of the C4 gene. By
      sequencing a C4A-specific lambda clone from a human genomic library containing
      the long intron 9 as well as PCR-amplified DNA containing the short intron, the
      DNA sequences of both introns were determined. The long and short introns have
      lengths of 6,787 bp and 415 bp, respectively. The sequence of the short intron is
      almost identical (96%) to the corresponding parts of the long intron. At position
      282 of the short intron, a 6,372-bp insertion is present in the long intron which
      has all characteristics of a full-length endogenous retrovirus. The proviral DNA
      is flanked by two 6-bp target site repeats. The orientation of the proviral
      sequence is opposite to that of the C4 coding strand. Long terminal repeats
      (LTRs) of 548 bp were found at both ends of the provirus. A TATA box and an SV40
      enhancer core as well as a polyadenylation signal are present in the LTR. A 5'
      primer binding site for lysine tRNA was identified. The strongest sequence
      homologies were found in comparison to human endogenous retrovirus (HERV-K):
      between 65-88% for gag, pol and env genes. However, a search for open reading
      frames in these regions indicated the presence of multiple stop codons in all
      three reading frames.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576719
TI  - Complement factor H mRNA in Epstein-Barr virus-transformed B lymphocytes of a
      factor H-deficient patient: detection by polymerase chain reaction.
AB  - A Spanish family with a hereditary deficiency of factor H was identified in
      previous studies. The deficiency was subtotal as low amounts of a dysmorphic
      molecule with partial identity to factor H were detected in her serum. The aim of
      this study was to obtain further characterisation of her deficiency employing her
      immortalised lymphocytes. After purification of mRNA from her Epstein-Barr virus
      (EBV)-transformed lymphocytes and from Raji cells, and cDNA synthesis we
      succeeded in amplifying cDNA which codes for factor H domains 13-15 from both
      cell lines, using specific oligonucleotides. The amplified fragments were
      indistinguishable from the one which was amplified from the control cloned cDNA
      template. The failure to amplify the 3' end of the patient's factor H mRNA
      suggests that the mRNA is truncated, which is consistent with the characteristics
      of the dysmorphic protein. Thus, factor H mRNA was detectable in Raji cells and
      the patient's EBV-transformed lymphocytes. We suggest that immortalised B
      lymphocytes can be used for the study of a range of inherited complement
      deficiencies.

PMID- 7576720
TI  - Immunoglobulin allotype frequencies in responders and nonresponders to the Rh(D)
      antigen.
AB  - Immunoglobulin allotype frequencies were determined in well characterised groups
      of responders (n = 160) and non-responders (n = 32) to Rh(D) antigen
      immunisation. Allotype frequencies in these groups were compared with frequencies
      in a normal control population (n = 500). No significant differences in allotype
      frequencies were observed between the responder and non-responder groups, or when
      these two groups where compared with a normal control population. These results
      suggest that the immunoglobulin heavy-chain genes do not influence the anti-Rh(D)
      immune response.

PMID- 7576721
TI  - Synergistic interaction between ORM1 and C3 types in disease associations.
AB  - In previous studies of orosomucoid (ORM) types and disease the ORM1 1 type has
      been found to be associated with sarcoidosis and other immunogenetic diseases,
      and the ORM 1 2 type with different types of carcinomas. We report significant
      associations between ORM1 and C3 types in sarcoidosis and breast cancer, but not
      in healthy individuals. The ORM1 1 and C3S variants in combination increased the
      risk of sarcoidosis, and the ORM1 2 and C3F variants together gave an increased
      risk of breast cancer. A probable mechanism may be that the ORM1 and C3 molecules
      modify the immune response by interacting with the lymphoid cell surface.

PMID- 7576717
TI  - Serum concentrations of C4 isotypes and factor B in type I C2 deficiency suggest
      haplotype-dependent quantitative expression of MHC class III complement genes.
AB  - The complement protein C4 exists as two isotypes, C4A and C4B, encoded by genes
      in the major histocompatibility complex (MHC) class III region. The serum
      concentrations of C4A4 were lower than those of C4B2 in serum from 19 individuals
      homozygous for type I C2 deficiency (p < 0.0002). These individuals all had the
      S042 complotype and most of them were homozygous for the haplotype HLA
      B18,S042,DR2. In 14 individuals heterozygous for the C2Q0 gene and with the C4A4,
      C4B2 phenotype and in 51 individuals with the C4A3, C4B1 phenotype, the isotype
      concentrations were equal. Factor B concentrations in the C2-deficient
      individuals were lower than those in individuals with the C4A3, C4B1 phenotype (p
      < 0.0001). The findings strongly suggest that the quantitative expression of C4
      isotypes and factor B is MHC haplotype dependent. C4 null alleles cannot be
      accurately determined by measuring relative C4 isotype serum concentrations.

PMID- 7576722
TI  - Detection of a 67-kD glycoprotein in human tumor cell lines by a monoclonal
      antibody established against a recombinant human endogenous retrovirus-K envelope
      gene-encoded protein.
AB  - Endogenous retroviruses in humans are discussed as putative etiologic agents in
      tumorigenesis. Molecular mimicry of cellular epitopes by retroviruses may be of
      importance for the genesis of autoimmune diseases. A group of human endogenous
      retroviruses, HERV-K, which is related to the mouse mammary tumour virus, has
      been characterised previously and open reading frames have been found covering
      their gag, pol, prt and env genes. Transcription of HERV-K genomes at the mRNA
      level as well as antibodies in human sera directed against HERV-K env have been
      detected recently. We have generated a monoclonal antibody (mAb), anti-HERV1,
      against a recombinant HERV-K Env protein. This mAb is capable of
      immunoprecipitating a 67-kD glycoprotein from the human breast carcinoma cell
      line T47D, the amount of which is strongly enhanced after stimulation with
      estradiol followed by progesterone. The same band could be precipitated from
      other carcinoma cell lines (Hep2, MCF7 and HeLa), but not from the human B
      lymphoblastoid cell line Raji and from cultured human fibroblasts. Incubation of
      this antigen in the presence of endoglycosidase F indicates the presence of N
      linked carbohydrate moieties of at least 7-9 kD.

PMID- 7576723
TI  - [Remembering Rio del Rio Hortega on th 50th anniversary of his death].

PMID- 7576726
TI  - Etiologic study of stroke in 95 young adults.
AB  - The aim of this prospective study was to determine the etiologic factors leading
      to stroke in a group of young adults. We studied 95 patients aged 50 years or
      under who were admitted with the diagnosis of stroke over a 2-year period. These
      patients underwent complete clinical and laboratory assessment for stroke. The
      etiology was established in 73 (76.8%) out of 95 cases. Arterial hypertension,
      embolism and atherosclerosis were found to be the most frequent causes in
      patients with ischemic stroke, whereas hypertension and aneurysm rupture were the
      most prevailing etiologies in patients with hemorrhagic stroke. Miscellaneous
      causes represented one fourth of all cases of the series. Coagulation
      abnormalities occurred in some patients, but in these cases there were also other
      well established causes. Paradoxical embolism was not observed. This study
      corroborates the importance of thorough diagnostic evaluation to establish an
      accurate diagnosis.

PMID- 7576725
TI  - [Cerebral cavernoma. A retrospective analysis of 24 cases].
AB  - We retrospectively analyzed 24 patients with cerebral cavernomas diagnosed
      according to histological and/or radiological criteria; epidemiological data,
      complementary techniques, therapy and evolution are reviewed and the cases are
      compared to those of previously reported series. Diagnosis was based on
      histological data in 18 patients and on magnetic resonance imaging (MRI) in the
      remaining 6. Five patients had compatible clinical histories symptoms compatible
      with the diagnosis. Mean age of the patients was 37.7 years, the most frequent
      location was the parietal lobe (27%), and seizures were the most common clinical
      symptoms of presentation (62%). Surgery was performed on 75%, sequelae were
      reported in 37.5% and exitus in 11%; 54% were asymptomatic. Six patients did not
      undergo surgery: 4 had multiple cavernomata, 1 received drug treatment that
      controlled the seizures and in 1 the cavernoma was located in the protuberance.
      We recommend the use of cerebral MRI for initial diagnosis, along with follow-up
      and investigation into similar profiles among family members. The treatment of
      choice is surgery in patients with acute, progressive or recurring deficits, and
      when lesions are superficial. At present there is no consensus about the
      treatment to follow when cavernomas are located in the brain stem.

PMID- 7576727
TI  - Multimodal evoked potentials in multiple system and late onset cerebellar
      atrophies.
AB  - Forty subjects were clinically examined using scales for cerebellar, pyramidal,
      parkinsonian, and mental status and by quantitative evaluation of neuroimages.
      The patients were classified into two groups: cerebellar-plus and "pure"
      cerebellar syndromes. Patients with "pure" cerebellar syndrome were diagnosed as
      autosomal dominant cerebellar ataxia III (ADCA III) or "pure idiopathic" late
      onset cerebellar ataxia (ILOCA) in this series. Patients with cerebellar-plus
      syndrome were diagnosed as multiple system atrophy (MSA), subclassified as either
      ILOCA-plus, ADCA I, ADCA II or autosomal recessive LOCA. We have used visual
      (VEP), brainstem auditory (BAEP) and somatosensory (SEP) evoked potentials in
      order to establish their diagnostic validity. Cerebellar-plus syndrome and "pure"
      cerebellar syndrome showed overlapping VEP, BAEP and SEP abnormalities. VEP P100
      latency, however, shows a certain ability to differentiate between the two groups
      (p = 0.08) and appears useful in distinguishing between sporadic cerebellar-plus
      syndromes (MSA or ILOCA-plus) and "pure" cerebellar syndromes (p < 0.02). The
      incidence of prolonged N9-N13 latency was significantly higher in the latter
      subgroup (p < 0.04) as well. Within cerebellar-plus syndromes, VEP, BAEP and SEP
      abnormalities were more frequent in inherited cases (ADCA I and II, along with
      autosomal recessive LOCA) than in sporadic ones. The most apparent differences
      were a higher incidence of abnormal BAEPs at brainstem level (p < 0.002), and of
      both peripheral and possible central SEP impairment in hereditary cerebellar-plus
      syndrome than in sporadic cerebellar-plus syndrome (p < 0.03). EP investigation
      is useful to a certain extent in differentiating between some variants of LOCA.

PMID- 7576728
TI  - [Microglia: past and present].

PMID- 7576729
TI  - [Recurrent confusional states and periodic lateralized epileptiform discharges: a
      new type of non-convulsive status epilepticus?].
AB  - Periodic lateralized epileptiform discharges (PLEDs) in an EEG usually indicate
      the presence of an underlying structural lesion (of vascular origin in most
      cases). PLEDs are also sometimes observed in certain types of infections (mainly
      viral), in which they may even constitute a characteristic finding useful for
      diagnostic purposes. In recent years cases have been reported in which PLEDs are
      linked to recurring confusional states that do not fit in with established
      classifications and that may be epileptic in nature. We discuss the cases of 2
      patients who were repeatedly admitted to our hospital in confusional states, in
      whom PLEDs were observed in EEG readings. Clinical evolution in both cases
      paralleled EEG alterations. We were able to perform both critical and
      intercritical single proton emission tomography on 1 patient, finding,
      respectively, hyper- and hypoabsorption foci. Symptoms resolved with
      antiepileptic treatment.

PMID- 7576724
TI  - [Scientific contributions of Pio del Hortega to neurosciences].

PMID- 7576730
TI  - [Ischemic neuropathy with conduction blocks].
AB  - We present a patient with a clinical picture of multiple mononeuropathy in which
      muscle and sural nerve biopsy revealed the existence of vasculitis compatible
      with panarteritis nodosa. Along with classical axonal lesion signs, we observed
      multifocal conduction blocks (CB) in all the nerves explored
      electrophysiologically. Topographic evolution was atypical in that distal BC
      disappeared earlier, whereas proximal BC appeared later and in all cases
      persisted longer. Ischemia may play a pathogenic role in BC along with other more
      well-known factors such as compression and immunological processes. BC detection
      would probably be less exceptional if, when ischemic neuropathy is suspected,
      patients were subjected to early and follow-up electrophysiological exploration
      that included proximal nerve segments.

PMID- 7576731
TI  - Babinski's sign: statistical validity of a classic sign in medicine.

PMID- 7576732
TI  - [Hypersomnia after tegmental pontine hematoma].

PMID- 7576733
TI  - [Occult spinal dysraphism].

PMID- 7576734
TI  - [Heparin therapy in acute ischemic infarction of the vertebrobasilar area].

PMID- 7576735
TI  - Special issue in honour of Nina and Jersy Einhorn in celebration of their 70th
      birthdays.

PMID- 7576736
TI  - A cohort study with regard to the risk of haematological malignancies in patients
      treated with x-rays for benign lesions in the locomotor system. I.
      Epidemiological analyses.
AB  - Roentgen treatment for painful benign conditions in the locomotor system as
      arthrosis and spondylosis was in Sweden very common up to the beginning of the
      1960s. The mode of treatment differed from the British ankylosing spondylitis
      series as smaller parts of the red bone marrow were exposed and smaller doses
      were applied. A cohort of 20,024 such patients treated 1950-1964 at two hospitals
      in northern Sweden was analysed with regard to the risk of haematological
      malignancies. Average factors for conversion of prescribed skin doses to mean
      absorbed red bone marrow doses were estimated on random samples of the different
      treatment sites and then applied on the cohort in its whole. The standard
      incidence ratio (SIR) for leukaemia was 1.18 (95% CI: 0.98-1.42) and the standard
      mortality ratio (SMR) 1.25 (0.99-1.45). In the highest dose group (mean absorbed
      red bone marrow dose > 0.5 Gy) the corresponding values were 1.40 (1.00-1.92) and
      1.50 (1.08-2.04). In the mortality analysis also a slightly increased myeloma
      risk was noted with SMR = 1.20 (0.99-1.56). Extension of the cohort and nested
      case-control studies are under progress.

PMID- 7576738
TI  - Risk of solid tumors after irradiation in infancy.
AB  - Cancer incidence was studied in 14,351 subjects exposed to ionizing radiation for
      skin hemangioma at the Radiumhemmet, 1920-1959. Record-linkage was done with the
      Swedish Cancer Registry for the period 1958-1986. After a mean follow-up of 39
      years, 300 cancers were observed and the standardized incidence ratio (SIR) was
      1.11 (95% confidence interval (CI) 0.99-1.24). The absorbed dose to different
      organs varied from < 0.01 Gy to > 40 Gy. The thyroid cancer incidence was
      significantly increased (SIR = 2.28; 95% CI 1.33-3.65) and for cancer of the
      breast SIR was 1.24 (95% CI 0.98-1.54). Regarding pancreatic cancer and tumors of
      the endocrine glands the statistically significantly increased SIRs were based on
      a small number of cases and might therefore only be a coincidence. No confirmed
      increased incidence could be established for other cancer sites.

PMID- 7576737
TI  - A cohort study with regard to the risk of haematological malignancies in patients
      treated with x-rays for benign lesions in the locomotor system. II. Estimation of
      absorbed dose in the red bone marrow.
AB  - A cohort study with regard to the risk of haematological malignancies was
      performed on about 20,000 patients who in 1950-1964 received roentgen treatment
      for benign conditions in the locomotor system. In order to estimate the mean
      absorbed red bone marrow dose the treatments were classified as concerning 10
      sites (cervical spine, thoracic spine, lumbar spine, sacral region, shoulder,
      hip, elbow, wrist, knee and ankle). The four last-mentioned sites do not normally
      contain red bone marrow in adults and their contribution to the mean absorbed
      dose was regarded as zero. For the other 6 sites random samples consisting of 30
      patients for each site were drawn from the cohort. By use of the treatment
      records and data from the literature on some physical parameters and red bone
      marrow distribution in normal adult persons, average conversion factors were
      calculated by which the subscribed surface dose could be converted into mean
      absorbed dose in red bone marrow. These conversion factors were then applied on
      the whole cohort and used for stratification of it according to different levels
      of exposure.

PMID- 7576739
TI  - Cancer incidence after radiotherapy for skin haemangioma during infancy.
AB  - An infant cohort treated for skin haemangioma with 226Ra between 1930 and 1965 (n
      = 11,807) was studied. The median age at treatment was 5-months and 88% were
      treated before 12 months of age. This cohort was followed up in the Swedish
      Cancer Registry during the years 1958 to 1989, giving 370,517 person-years at
      risk. A total number of 248 malignancies have been observed and the standardized
      incidence ratio (SIR) was 1.21 (confidence interval (CI) 95%, 1.06-1.37).
      Significantly increased numbers of cancers were found in the central nervous
      system, 34 cases (SIR = 1.85, CI 95% 1.28-2.59), the thyroid, 15 cases (SIR =
      1.88, CI 95% 1.05-3.09) and other endocrine glands, 23 cases (SIR = 2.58, CI 95%
      1.64-3.87). The absorbed dose in 11 specified risk organs has been estimated
      using a phantom of the size of a 5-6-month-old child. The mean absorbed dose in
      the thyroid was 0.12 Gy and the excess relative risk (ERR) for thyroid cancer was
      7.5 per Gy (CI 95% 0.4-18.1). The mean dose in the central nervous system was
      0.077 Gy and the ERR for brain tumours was 10.9 per Gy (CI 95% 3.7-20.5). This
      cohort gives a unique opportunity to analyse long-term effects of low-dose
      irradiation during infancy.

PMID- 7576740
TI  - Acetaminophen, some other drugs, some diseases and the risk of transitional cell
      carcinoma. A population-based case-control study.
AB  - The purpose of this study was to investigate the risk of transitional cell
      carcinoma among subjects with an intake of acetaminophen, aspirin, some other
      drugs and with some intercurrent diseases. The source person-time ('study base')
      included subjects living in Stockholm in 1985-1987. The study included 325
      subjects with a transitional cell carcinoma of the urinary tract and 393 controls
      randomly selected from the source person-time. Data were obtained by a postal
      questionnaire supplemented by a telephone interview. A relative risk (with a 95%
      confidence interval) of 1.6 (1.1-2.3) was obtained after an intake of
      acetaminophen, adjusted for age, aspirin, gender and smoking. Conversely, a 30%
      decrease in risk was obtained after an intake of aspirin. No details in the
      exposure substantiated the finding for acetaminophen. The inherent validity
      problems of observational studies, and the weak evidence in this and previous
      studies of the association between acetaminophen and transitional cell carcinoma,
      makes available epidemiological evidence insufficient to regulate the use of this
      commonly ingested analgesic. Increased risks were, in addition, found for
      tetracyclines, nitrofurantoin and a history of allergic asthma and a decreased
      risk found for rheumatic symptoms. The findings stress the nonepidemiological
      data concerning the potential carcinogenicity of acetaminophen and may be a
      foundation for future research of some other drugs and diseases.

PMID- 7576741
TI  - Parenchymal-stromal interactions in neoplasia. Theoretical considerations and
      observations in melanocytic neoplasia.
AB  - The paper briefly reviews the reciprocal and continuous reciprocal interactions
      between epithelia, mesenchyme, and extracellular matrix in the development and
      maintenance of organismal form in multicellular organisms in the animal kingdom
      and describes the progressive changes in parenchymalstromal interactions in
      melanocytic neoplastic development and progression. In addition to the
      parenchymal stromal form in non-lesional skin seven different and unique stromal
      patterns are described. These have been termed: 1) The stroma (diff-regress) of
      programmed differentiation leading to lesional regression characteristic of
      common nevi; 2) concentric eosinophilic fibroplasia (cef), the hallmark of
      precursor nevi (dyplastic nevi) with and without melanocytic nuclear atypia; 3)
      Fibroplasia with angiogenesis (fa) commonly seen in superficial spreading
      melanoma without metastic competence (SSM); 4) Lamellar fibroplasia (lf) seen in
      precursor nevi and melanomas with and without metastatic competence; 5) Diffuse
      fibroplasia with angiogenesis (dfa), 6) Narrow, uniform concentric eosinophilic
      fibroplasia (nucef), 7) No parenchymal-stromal interaction (nopsi); the last
      three being seen in the heterogeneous stroma of melanomas of the superficial
      spreading type with metastatic competence. The changes in neoplastic stroma
      proceed in concert with the changes in the parenchyma characteristic of
      melanocytic tumor progression.

PMID- 7576742
TI  - Glutathione transferase P1-1 expression in human melanoma metastases: correlation
      to N-RAS mutations and expression.
AB  - Expression of the detoxication enzyme glutathione transferase P1-1 (GST P1-1) at
      elevated levels has been noted in many types of human tumors, including
      melanomas. The products of the human H-RAS, K-RAS and N-RAS genes play a key role
      in intracellular signal transduction leading to transcriptional activation of AP
      1 (Fos/Jun) responsive genes. The oncogenic mutated forms of the ras proteins are
      constitutively active and interfere with normal signal transduction. Mutated RAS
      genes as well as increased expression of wild-type ras proteins are common
      features in human tumors including melanoma. We have characterized 30 melanoma
      metastases from 23 melanoma patients with reference to N-RAS expression and
      mutation as well as to GST P1 expression (immunohistochemistry and genetic
      analysis). Twenty-three of 30 samples (70%) had high N-Ras p21 and/or N-RAS codon
      61 mutations and 18 of these 23 samples also had high GST P1-1 immunoreactivity.
      Seven of 30 (23%) samples had low N-Ras p21 immunoreactivity and no detectable N
      RAS codon 61 mutations. Six of these 7 samples (86%) also had low GST P1-1
      immunoreactivity. The results indicate a statistically significant correlation
      (Spearman correlation coefficient, r = 0.56, p = 0.001, 2-tailed test) and
      provide, for the first time, indirect evidence for a possible coregulation of N
      RAS and GST P1 in human malignant melanoma which should be further evaluated.

PMID- 7576743
TI  - p53 expression and the result of adjuvant therapy of breast cancer.
AB  - Functional p53 protein is essential for the cellular response to drug-induced DNA
      damage. We investigated p53 accumulation in tumour specimens from premenopausal
      breast cancer patients who were randomised to adjuvant chemotherapy (CMF) or
      postoperative radiotherapy. Of the tumours from 139 patients, 20 showed abnormal
      accumulation as judged with immunohistochemistry (> 10% positive tumour cells).
      The risk of distant recurrence was similar in the two treatment groups for
      patients whose primary tumours lacked p53 accumulation, whereas there was a
      significant benefit from CMF for patients showing abnormal accumulation (relative
      risk 0.18, 95% CI, 0.04-0.93). This result suggests that p53-dependent apoptosis
      is not a general mechanism by which breast cancer cells respond during CMF
      chemotherapy.

PMID- 7576744
TI  - Increased risk of second primary malignancies in patients with gynecological
      cancer. A Swedish record-linkage study.
AB  - The Stockholm-Gotland Cancer Register was used to study the risk of developing
      second primary malignancies (SPM) in women diagnosed with cancer of the uterine
      cervix, uterine corpus and ovaries during the period 1958-1992. Among 5,325
      patients with uterine cervix cancer, 619 developed SPM. Standardized incidence
      ratio (SIR) was 1.29 (95% confidence interval (CI) 1.19-1.39). Significantly
      increased risks were observed for cancer of the colon, rectum, lung, vulva,
      kidney and bladder. A total of 4,815 women with uterine corpus cancer were
      followed and 660 SPM were found. The overall SIR was 1.21 (95% CI 1.12-1.30) with
      significantly increased risk for cancer of the colon, ovary, vulva and bladder.
      The incidence of leukemia was also significantly elevated (SIR = 3.03; 95% CI
      1.70-5.00). Among 5,060 patients with ovarian cancer, 379 SPM were found (SIR
      1.49; 95% CI 1.34-1.64). Increased risks of cancer of the colon, rectum, breast,
      uterine corpus, bladder and leukemia were observed. All three primary sites
      showed elevated risks of cancer of the colon and bladder. For patients with a
      primary cancer of the corpus and ovary an elevated risk of leukemia was also
      noted. The conclusion from these findings is that SPM to some extent can be
      explained by previously known factors, i.e. treatment and common risk factors.
      However, further studies concerning the role of common etiology, for instance
      hereditary and hormonal factors, are needed to increase the knowledge on the
      etiology of second primary malignancies.

PMID- 7576746
TI  - The role of cul-de-sac aspiration cytology in the follow-up of ovarian cancer.
AB  - The methods most often used for follow-up of ovarian cancer are physical
      examination, CA-125 measurement and ultrasonography or computed tomography. In
      the present study the role of cul-de-sac aspiration cytology as a supplementary
      method was evaluated. We analyzed the records of 110 stage I-IV ovarian cancer
      patients who had undergone cul-de-sac aspiration as a part of their follow-up
      schedule after the primary treatment. During the median follow-up of 5 years
      altogether 577 cul-de-sac aspirations were performed with a median interval of 9
      months. Only in 2 cases the obtained sample was insufficient for evaluation.
      Twenty patients had cul-de-sac cytology > or = class III at some point during the
      follow-up. In 12 cases the preceding or subsequent CA-125 values taken within 3
      months were < 35 U/l. In 7 cases CA-125 values increased later, but in 5 cases
      the tumour marker values remained within normal range during the entire follow
      up. Nine out of these 12 patients had a clinical recurrence later on, but 3
      patients had no evidence of the disease. Twenty-seven recurrences were detected
      during the follow-up. Cul-de-sac aspiration cytology was the first or the only
      indication of recurrence in 9 cases (33%) and is a useful supplementary method in
      the follow-up of ovarian cancer.

PMID- 7576745
TI  - Value of uterine artery Doppler in endometrial cancer.
AB  - Twenty-seven women with endometrial cancer were studied with Doppler ultrasound
      coupled with a vaginal probe. Pulsatility index of the flow velocity of the
      uterine artery was recorded and compared to that of a control group. The subjects
      and the controls did not differ in blood flow measurements. There was no
      correlation between severity of disease and flow velocimetry values. Eleven of
      the patients underwent brachytherapy prior to surgery. Administration of
      brachytherapy resulted in a decrease of the peripheral resistance. The results of
      this study indicate that Doppler velocimetry of the uterine artery is not a
      valuable tool in discriminating between malignant and benign endometrium.

PMID- 7576747
TI  - Prognostic value of pretreatment factors in patients with locally advanced
      carcinoma of the uterine cervix treated by radiotherapy alone.
AB  - The prognostic effect of pretreatment patient- and tumor characteristics, and the
      influence of radiotherapy schedule on local control, distant metastases, and
      crude survival were analyzed in 424 consecutive patients with FIGO stage IIB (n =
      137), IIIA (n = 10), IIIB (n = 211) and IVA (n = 66) cancer of the uterine
      cervix. All patients were given radiotherapy alone. From 1974 and through 1977,
      the external and intracavitary combined radiotherapy was given continuously in 4
      to 6 weeks. From 1978 and through 1983, the treatment policy was changed to split
      course radiotherapy by introducing planned pauses, resulting in an overall
      treatment time of 10 to 12 weeks. The results were estimated by univariate
      actuarial- and Cox multivariate regression analyses. Multivariate analysis showed
      that significant adverse variables for local control were large lateral tumor
      diameter, young age, low hemoglobin at time of admission, many pregnancies, split
      course strategy, and high FIGO stage. Risk of metastases increased with
      decreasing hemoglobin, increasing malignancy grade and split-course treatment.
      Poor survival probability were related to large lateral tumor diameter, high
      malignancy grade and FIGO stage, low hemoglobin, split-course therapy, and
      adeno/adenosquamous tumor type.

PMID- 7576748
TI  - The prognostic significance of stage, tumor size, cellular atypia and DNA ploidy
      in uterine leiomyosarcoma.
AB  - To analyze the significance of DNA ploidy in uterine leiomyosarcoma, the
      traditional clinical and histopathological prognostic variables and DNA ploidy
      were studied in 70 patients with histologically verified uterine leiomyosarcoma.
      Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the
      tumor were obtained in 58 patients. In univariate analysis tumor diameter, FIGO
      stage and presence of residual disease after primary surgery were highly
      significant (p < 0.001) and also DNA ploidy (p = 0.043), age (p = 0.017), and
      menopause status (p = 0.028) obtained significance. Cellular atypia was almost
      significant (p = 0.056), while mitotic count, malignancy grade and vessel
      invasion were not. In Cox's multivariate analysis, FIGO-stage was found to be the
      most important prognostic factor (p < 0.001), followed by cellular atypia (p =
      0.007) and tumor diameter (p = 0.016). DNA ploidy did not obtain significance
      when categorized as diploid/non-diploid. Patients with tumors with multiple
      aneuploid cell populations had a very poor prognosis. When categorized as
      multiple aneuploidy versus all other ploidy groups, DNA ploidy obtained marginal
      significance in multivariate analysis (p = 0.054). Tumor diameter, stage and
      cellular atypia are important prognostic parameters in uterine leiomyosarcomas.

PMID- 7576749
TI  - The prognostic information of DNA ploidy and S-phase fraction may vary with
      histologic grade in endometrial carcinoma.
AB  - DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on
      paraffin-embedded tumor material from 243 patients treated during 1980-1985.
      Patients with well differentiated and moderately differentiated tumors without
      solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%).
      Twenty-four patients, dead of disease within 5 years, were compared with 52
      survivors. The estimated death risk was higher for those with SPF > or = 8.0%
      compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the
      only independent prognostic factor in a multivariate analysis also including age,
      clinical stage and grade of differentiation. Patients with moderately
      differentiated tumors with solid areas or poorly differentiated tumors (n = 208)
      were regarded as a high-risk group. There was a difference in survival according
      to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid
      tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a
      multivariate analysis DNA ploidy, age and clinical stage were independent
      prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and
      SPF have different prognostic values depending on histological grade of
      endometrial carcinoma.

PMID- 7576750
TI  - Experience with hormonal therapy in advanced epithelial ovarian cancer.
AB  - The experience from using different hormonal trials in 33 ovarian cancer
      patients, who were beyond the stage of standard therapies and experimental
      cytotoxic therapies in a single institution, are reported. Agents used were
      progestins, an antiestrogen (tamoxifen), an antiandrogen (flutamide) and a GnRH
      agonist (decapeptyl). Twenty-one patients completed at least 8 weeks of
      treatment. Two patients obtained an objective response (10%): one partial
      response on tamoxifen for 6 months and one complete response on decapeptyl for 38
      + months. Two further patients achieved disease stabilizations on tamoxifen and
      flutamide for 6 and 8 months respectively. Although the objective response rate
      with hormonal therapies is limited in these circumstances the absence of
      important toxicities favor their use. It is suggested to further study this in
      patients who do not reach a complete response after standard induction
      chemotherapy, particularly in those with well-differentiated tumors.

PMID- 7576751
TI  - Carboplatin in combination with epirubicin and cyclophosphamide in patients with
      advanced ovarian cancer. A phase II study.
AB  - Seventy-one patients with epithelial ovarian cancer stage III (n = 56) or IV (n =
      15) were treated with carboplatin 300 mg/m2, epirubicin 50 mg/m2 and
      cyclophosphamide 400 mg/m2 every fourth week. Patients clinically free of tumour
      after six courses (n = 58) underwent a second-look laparotomy. Seventeen patients
      were microscopically tumour-free (24% of all) and an additional 10 (14%) had only
      microscopic cancer. Median time to progression was 19 months. The median survival
      was 33 months and the estimated 5-year survival 27%. The toxicity was mainly
      haematological, with leukopenia WHO grade 3-4 seen in 88% and thrombocytopenia
      grade 3-4 in 42% of the patients. The gastrointestinal toxicity was mild and no
      renal toxicity was seen. This chemotherapy regimen was effective with acceptable
      toxicity and could be given on an out-patient basis. The possibility of
      increasing the efficacy and decreasing the toxicity was discussed.

PMID- 7576752
TI  - Quality assurance network in central Europe. External audit on output calibration
      for photon beams.
AB  - The EROPAQ project for TLD monitoring of photon beams started in June 1994 with
      the set-up of the TLD system: calibration, reading and evaluation procedures. The
      acceptance level of +/- 3% was set for the TLD intercomparisons. The policy of
      the project was to check all beams in 47 participating radiotherapy centres and
      to recheck all the beams in those centres, where a deviation exceeding +/- 3%
      occurred in one or more of the beams. Out of 129 beams checked, 100 beams (78%)
      were found within the +/- 3% limit. Eleven beams show deviations larger than +/-
      6%, and immediate corrective action was undertaken. Out of 47 centres checked, 22
      did not participate in any external audit in a preceding 5 years. In these
      centres 68% (34/50) of the total number of gamma and x-ray beams checked but only
      59% (20/34) of gamma beams were within the acceptance level, while in the 25
      centres, which participated in an external audit before, these figures were 84%
      (66/79) and 88% (35/40) respectively. The sources of discrepancies were
      thoroughly investigated, discussed with the participants and the errors
      corrected. Poor results were in several cases associated with very old design of
      radiotherapy units and old dosimetry systems, equipped with inadequate ionization
      chambers. In several centres, an insufficient training of the physicists in
      clinical dosimetry was observed. Thanks to the corrective action, a great
      improvement of calibration of the beams was achieved. Standard deviation of the
      distribution of the results for all x and gamma beams checked decreased from SD =
      7.4% at the first check to SD = 2.5% at the second check.

PMID- 7576753
TI  - The importance of local control in the conservative treatment of breast cancer.
AB  - The purpose of this study was to examine the meaning of local control, especially
      on survival, in breast cancer patients treated by lumpectomy with or without
      radiotherapy. We analyzed the survival results of four major published randomized
      trials that compare conservation surgery with or without radiation using three
      different statistical approaches: p-values, confidence intervals, and Bayesian
      techniques. All four trials report statistically significant increased local
      control and improved survival for the irradiated patients. Survival based on p
      values and confidence intervals shows statistical significance for long-term
      follow-up of the NSABP-B06 trial, but not for the other trials, probably because
      of small sample sizes and short follow-up. At 10 years, the overall survival
      rates for the NSABP-B06 were 65% and 71% for lumpectomy alone or with radiation
      respectively. Interpreted in a Bayesian framework, the expected advantage in 10
      year survival was 6% (the mean of NSABP-B06 10-year survival) with an 83%
      probability that the 10-year survival difference may lie between 2% and 10%. An
      85% probability that 3% of patients will survive at 10 years because of
      irradiation translates into a 30% reduction in annual odds of death several years
      after treatment in stage I good prognosis patients and 15% in stage I poor
      prognosis patients. Analysis of the randomized trials comparing lumpectomy with
      or without radiation indicate a clear improvement in survival for the irradiated
      patients associated with increased local control. Combination of improved
      survival with the reduced psychological and economic costs associated with local
      recurrence argues well for the inclusion of radiation for many breast cancer
      patients.

PMID- 7576754
TI  - Influence of radiation therapy on lung tissue in breast cancer patients. CT
      assessed density changes 4 years after completion of radiotherapy.
AB  - CT-assessed density changes in lung tissues were measured in 22 disease-free
      breast cancer patients 4 years after completion of radiation therapy. All
      patients had previously undergone similar CT-examinations before treatment, 3
      months, and 9 months after radiotherapy. In patients with visible areas of
      increased lung density at earlier CT-examinations a decrease of focal findings
      was observed at 4 years. In patients without focal findings, an increase in
      density relative to that before therapy was observed. The difference between the
      mean lung density values among those with visible radiological findings and those
      without was statistically significant both at 3 and 9 months after therapy.
      However, this difference did not persist at 4 years. These results may indicate a
      2-phase development of radiation-induced lung damages--an acute phase and a late
      phase; the late phase emerging slowly, and in this study detectable 4 years after
      completion of radiation therapy.

PMID- 7576755
TI  - Volume and heterogeneity dependence of the dose-response relationship for head
      and neck tumours.
AB  - Based on the Poisson statistics of cell kill a model for the response of
      heterogeneous tumours to non-uniform dose delivery have been developed. The five
      parameters required to characterize the response are the 50% response dose, D50,
      the normalized dose-response gradient, gamma, the tumour heterogeneity factor, h,
      the relative volume, v and the extra daily dose required to counteract the tumour
      cell proliferation, delta. The model has been fitted to data from a number of
      clinical investigations to allow the derivation of clinically relevant radiation
      response parameters for head and neck tumours. The D50 value for T2 larynx
      cancers is 59.9 Gy in 41 days with a relative standard deviation of 2.1 Gy and
      the gamma value is 2.9 with a relative standard deviation of 0.3. The value of
      delta, which is most consistent with the clinical data for laryngeal tumours, is
      0.35 Gy/day and this value should be used if the treatment time is changed from
      the 41 days normalization. The heterogeneity factor, h, is close to zero for
      laryngeal tumours which indicates that their response is basically governed by
      Poisson statistics. Nasopharyngeal tumours, on the other hand, exhibit h values
      around 0.2 which indicates that these tumours are more heterogeneous in their
      internal organization and so are their responses to radiation.

PMID- 7576756
TI  - Stereotactic high dose fraction radiation therapy of extracranial tumors using an
      accelerator. Clinical experience of the first thirty-one patients.
AB  - A stereotactic body frame with a fixation device has been developed for
      stereotactic radiation therapy of extracranial targets, a precision localization
      and positioning system in analogy with the stereotactic head frames used for
      intracranial targets. Results of the first 42 treated tumors in 31 patients are
      presented. Most of the patients had solitary tumors in liver, lung or
      retroperitoneal space. Clinical target volumes ranged from 2 to 622 cm3 (mean 78
      cm3) and minimum doses to the planning target volumes (PTV) of 7.7-30 Gy/fraction
      (mean 14.2 Gy) were given on 1-4 occasions to a total minimum dose to the PTVs of
      7.7-45 Gy (mean 30.2 Gy) to the periphery of the PTV and total mean doses to the
      PTVs of 8-66 Gy (mean 41 Gy). The central part of the tumor was usually given
      about 50% higher dose compared to that of the periphery of the PTV by a planned
      inhomogeneous dose distribution. Some of the patients received stereotactic
      radiation therapy concomitantly to more than one target, in others new metastases
      were also treated which appeared during the follow-up period. We observed a local
      rate of no progressive disease of 80% during a follow-up period of 1.5-38 months.
      Fifty percent of the tumors decreased in size or disappeared.

PMID- 7576757
TI  - Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity
      induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in
      vitro.
AB  - At cancer treatment, the use of antiemetics are often needed due to induction of
      nausea and vomiting. Some antiemetics have been shown to interact with the direct
      cytotoxic effects. The newly developed antiemetics have, as far as we know, not
      been studied in this respect. In the present study, the effects of the 5-HT3
      receptor antagonists ondansetron and granisetron were evaluated on the
      cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and
      cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro.
      Ondansetron or granisetron (10(-5) mol/l) had no effect on the survival of
      irradiated cells. Granisetron (10(-5) mol/l) significantly potentiated
      cytotoxicity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of
      granisetron (10(-7) mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and
      estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non
      interactive with the cytotoxicity induced by any of the anti-cancer drugs.
      Although the encountered observation with an enhancing effect of granisetron on
      the epirubicin-induced cytotoxicity is seen in a specific experimental situation
      in vitro, the fact that 5-HT3 receptor antagonists are routinely used during
      cancer treatment indicate that attention should be given to a possible
      interaction with the antineoplastic action of cancer treatment.

PMID- 7576759
TI  - [Tissue Doppler echocardiography].

PMID- 7576758
TI  - Long-term adjuvant interferon treatment of human osteosarcoma. A pilot study.
AB  - During the period from 1971 to 1990 all osteosarcoma patients referred to the
      Karolinska Hospital without signs of metastases received human leukocyte
      interferon (IFN) as adjuvant treatment. Patients referred between 1985 and 1990
      were given more intensive human leukocyte IFN treatment, i.e. a standard dose of
      3 MU s.c. daily for 3-5 years. These 19 patients, all followed for 5 years, were
      included in a pilot study which entailed patients with central localization where
      radical surgery was not feasible. Metastases developed in 9 patients, of whom 3
      had local recurrences. Sixty-three percent are free of disease at 5 years. Side
      effects were negligible and long-term toxicity practically non-existent. It is
      suggested that a randomized multicenter IFN trial should be instituted on
      patients with poor prognosis receiving chemotherapy and/or that IFN treatment
      should be combined with other therapeutic modalities--irradiation, chemotherapy
      or anti-angiogenic substances--in osteosarcoma.

PMID- 7576760
TI  - [Cardiac tissue Doppler. A new noninvasive technic for analysing myocardial wall
      function].

PMID- 7576761
TI  - [Tissue Doppler echocardiography: a new stage in the study of myocardial
      function].
AB  - Tissue Doppler echocardiography is a new technique that allows selective
      visualization and measurement of myocardial velocities, affording a new
      perspective on cardiac function. It has been showing promising and exciting
      preliminary results on coronary artery disease, hemodynamics, cardiomyopathies,
      right ventricular and aortic diseases and arrhythmias, opening a new era in the
      analysis of regional myocardial function.

PMID- 7576762
TI  - [The spectral analysis of heart rate variability. A comparative study between
      nonparametric and parametric spectral analysis in short series].
AB  - OBJECTIVE: to compare parametric (AR) and non parametric (FFT) spectral analysis
      results obtained in 512 beats series. INTERVENTIONS: 104 healthy subjects with
      normal physical examination and electrocardiogram were studied. The Ecg was
      recorded at rest, with controlled breathing at 15 cycles/min., and sampled at 300
      Hz. The spectral VLF, LF and HF were calculated with FFT algorithm. For the same
      series, an auto-regressive analysis (AR) with optimized choice of the order of
      the model (AIC criterion) have been computed, VLF, LF and HF components were
      identified by AR spectral decomposition. RESULTS: In both groups, athletes and
      sedentary, there were no statistically differences between VLF, LF, HF and LF/HF
      spectral indices computed by the two methods. CONCLUSION: the results suggest
      that with controlled breathing it does not seems to exist any advantage in the
      use of AR spectral analysis to compute spectral components of heart rate
      variability, which is much more laborious that fixed bands non parametric FFT
      analysis.

PMID- 7576763
TI  - [The evolution of the arterial pressure during a stress test in patients with
      hypertrophic myocardiopathy].
AB  - OBJECTIVES: To study the exercise blood pressure response in patients with
      hypertrophic cardiomyopathy (HC) and its relationship with sudden death. DESIGN:
      Retrospective study. POPULATION: We studied 51 patients (P) with HC: 18 women and
      33 men. Their average age was 45 +/- 14 years, with a mean follow-up of 55 +/- 37
      months. METHODS: Every patient had been subjected to a treadmill stress-test, a
      24-hour Holter monitoring and an echocardiographic examination. Particular
      emphasis was given to blood pressure increments (BPI) during stress-test, the
      existence of premature ventricular contractions with a frequency of 10 or more
      per hour (PVC > or = 10), the occurrence of couplets (C) and/or non-sustained
      ventricular tachycardia (NSVT) on a 24-hour Holter. Finally, the finding of
      systolic anterior motion (SAM) of the mitral valve, in the routine
      echocardiogram, was valued. RESULTS: Four patterns of BPI were identified: "1":
      normal evolution (27 P); "2": plateau type increment (16 P); "3": fall in blood
      pressure during exercise (6 P); "4": abnormal BPI during recovery (2 P). Two
      groups were considered: group N-normal BPI, group A-patients with abnormal blood
      pressure responses. There were no significant differences among therapeutic
      agents, between the two groups, when the stress-test was performed. SAM was found
      in 21 P. Only 8 P registered ventricular arrhythmias, half of them with NSVT. No
      statistical relations were found between BPI and P age, the presence of SAM, PVC
      > or = 10, C, or NSVT. We found 78% of P in group N in NYHA class I. In contrast,
      in group A only 46% were in class I (p = 0.04). Only one death, of non cardiac
      cause, occurred (group A). CONCLUSIONS: There is a large number of patients with
      HC and abnormal BPI. This is, seemingly, not influenced either by a dynamic left
      ventricular gradient or by ventricular ectopic beat occurrence. However, a
      relation appears to exist between the abnormal response and functional class, not
      explained by the usual (noninvasive) clinical tests.

PMID- 7576764
TI  - [Acute and chronic sequential atrioventricular pacing in patients with
      obstructive-type hypertrophic myocardiopathy resistant to medical therapy].
AB  - An evaluation was undertaken regarding two female patients suffering from
      obstructive hypertrophic cardiomyopathy, with high and strongly symptomatic
      gradients, as well as evidencing a resistance to medication with beta-blockers,
      verapamil and disopyramide when administered in maximal doses. These patients
      were provided with the implant of a definitive type DDD pacemaker, with an
      auricular electrocatheter placed on the right auricular appendix, and with a
      bipolar ventricular catheter placed on the apex of the right ventricle. The
      generator was programmed with a short AV so as to ensure that the ventricular
      stimulation would at any given time be the result of the ventricular contraction
      would be initiated at the apex portion of the right ventricle. With these
      therapeutics, we observed not only a reduction or even the gradient, but also the
      complete elimination of the existing symptoms--angor, dyspnea, dizziness,
      palpitations and fainting--with the resulting normalcy of the quality of life of
      the patients. All taken into account we are of the opinion that these
      therapeutics are, in the case of patients suffering from obstructive hypertrophic
      cardiomyopathy, a valid alternative for surgical treatment by means of myectomy
      or myotomy, but without the morbidity and mortality rates presented by such
      methods.

PMID- 7576765
TI  - [Acute juvenile myocardial infarct. A clinical case and review of the
      literature].
AB  - Authors report one case of myocardial infarction in a young man 23 years old.
      Prevalence of acute myocardial infarction under the age of 35-40 years is not
      negligible. Pathogenic mechanisms, risk factors, clinical presentation,
      prognosis, and findings in selective coronary angiography are reviewed.

PMID- 7576766
TI  - [Sudden death in hypertrophic myocardiopathy].
AB  - Sudden death is a very important event in the natural history of hypertrophic
      cardiomyopathy. Although its physiopathology is not still fully understood, there
      are several potential mechanisms to explain it, such as electrical, ischemic and
      hemodynamic events. It is thought that these mechanisms vary from patient to
      patient and that more than one mechanism may coexist in a specific patient. Risk
      factors for sudden death in hypertrophic cardiomyopathy are clinical, genetical
      and electrical. Risk stratification implies aggressive investigation
      (electrophysiological study and/or forearm plethysmography during exercise and/or
      tilt test) in order to identify the most probable mechanism involved in each case
      and to select individualized preventive measures (pharmacological, surgical,
      implantable cardioverter defibrillator). The role of amiodarone is still
      controversial because of contradictory results with this drug in this illness.

PMID- 7576768
TI  - Alcohol dehydrogenase: multiplicity and relatedness in the solvent-producing
      clostridia.
AB  - Alcohol dehydrogenase (ADH) is a key enzyme for the production of butanol,
      ethanol, and isopropanol by the solvent-producing clostridia. Initial studies of
      ADH in extracts of several strains of Clostridium acetobutylicum and C.
      beijerinckii gave conflicting molecular properties. A more coherent picture has
      emerged because of the following results: (i) identification of ADHs with
      different coenzyme specificities in these species; (ii) discovery of structurally
      conserved ADHs (type 3) in three solvent-producing species; (iii) isolation of
      mutants with deficiencies in butanol production and restoration of butanol
      production with a cloned alcohol/aldehyde dehydrogenase gene; and (iv) resolution
      of various 'C. acetobutylicum' cultures into four species. The three ADH isozymes
      of C. beijerinckii NRRL B592 have high sequence similarities to ADH-1 of
      Clostridium sp. NCP 262 (formerly C. acetobutylicum P262) and to the ADH domain
      of the alcohol/aldehyde dehydrogenase of C. acetobutylicum ATCC 824/DSM 792. The
      NADH-dependent activity of the ADHs from C. beijerinckii NRRL B592 and the BDHs
      from C. acetobutylicum ATCC 824 is profoundly affected by the pH of the assay,
      and the relative importance of NADH and NADPH to butanol production may be
      misappraised when NAD(P)H-dependent activities were measured at different pH
      values. The primary/secondary ADH of isopropanol-producing C. beijerinckii is a
      type-1 enzyme and is highly conserved in Thermoanaerobacter brockii (formerly
      Thermoanaerobium brockii) and Entamoeba histolytica. Several solvent-forming
      enzymes (primary ADH, aldehyde dehydrogenase, and 3-hydroxybutyryl-CoA
      dehydrogenase) are very similar between C. beijerinckii and the species
      represented by Clostridium sp. NCP 262 and NRRL B643. The realization of such
      relationships will facilitate the elucidation of the roles of different ADHs
      because each type of ADH can now be studied in an organism most amenable to
      experimental manipulations.

PMID- 7576767
TI  - Solventogenic enzymes of Clostridium acetobutylicum: catalytic properties,
      genetic organization, and transcriptional regulation.
AB  - The enzymes acetoacetate decarboxylase and coenzyme A transferase catalyse
      acetone production from acetoacetyl-CoA in Clostridium acetobutylicum. The adc
      gene encoding the former enzyme is organized in a monocistronic operon, while the
      ctf genes form a common transcription unit with the gene (adhE) encoding a
      probable polyfunctional aldehyde/alcohol dehydrogenase. This genetic arrangement
      could reflect physiological requirements at the onset of solventogenesis. In
      addition to AdhE, two butanol dehydrogenase isozymes and a thiolase are involved
      in butanol synthesis. RNA analyses showed a sequential order of induction for the
      different butanol dehydrogenase genes, indicating an in vivo function of BdhI in
      low level butanol formation. The physiological roles of AdhE and BdhII most
      likely involve high level butanol formation, with AdhE being responsible for the
      onset of solventogenesis and BdhII ensuring continued butanol production.
      Addition of methyl viologen results in artificially induced butanol synthesis
      which seems to be mediated by a still unknown set of enzymes. Although the signal
      that triggers the shift to solventogenesis has not yet been elucidated, recent
      investigations suggest a possible function of DNA supercoiling as a
      transcriptional sensor of the respective environmental stimuli.

PMID- 7576769
TI  - Molecular genetics and the initiation of solventogenesis in Clostridium
      beijerinckii (formerly Clostridium acetobutylicum) NCIMB 8052.
AB  - A physical map of the Clostridium beijerinckii (formerly Clostridium
      acetobutylicum) NCIMB 8052 chromosome has been constructed, encompassing about 90
      rare restriction sites. The 14 rrn operons together with about 40 genes have been
      assigned positions on the map. Genetic analysis and gene transfer have been
      developed in this organism to enable in vivo analysis of the roles of cloned
      genes using marker replacement technology. Experiments using the available
      genetic tools have shown that spo0A plays a cardinal role in controlling several
      aspects of the transition from exponential growth to stationary phase in C.
      beijerinckii. These include initiation of sporulation, accumulation of the
      storage polysaccharide, granulose, and production of acetone and butanol. Several
      C. beijerinckii and C. acetobutylicum genes concerned with fermentative
      metabolism, whose expression is modulated at the onset of solventogenesis,
      contain sequence motifs resembling 0A boxes in their 5' regulatory regions. This
      invites the speculation that they are under the direct control of Spo0A, and
      additional data are now required to test this prediction.

PMID- 7576771
TI  - Sigma factor and sporulation genes in Clostridium.
AB  - The genus Clostridium, represented by Gram-positive, anaerobic, spore-forming
      bacteria, is well known for its clinical importance and considerable
      biotechnological potential. Recently, evidence for a functional role of the
      transcription factors sigma A, sigma E, sigma G, and sigma K in this genus was
      provided by cloning and sequencing these genes from C. acetobutylicum. In C.
      kluyveri, a partially sequenced open reading frame was found to encode the N
      terminus of the putative sigma factor L with significant similarity to members of
      the sigma 54 family. The identification of sequences with high similarity to the
      Bacillus sigma F (C. acetobutylicum), sigma H (several clostridial species), and
      sigma D (C. thermocellum)-controlled consensus promoters renders the existence of
      these transcription factors in clostridia very likely. These data are in
      agreement with information obtained by RNA transcript mapping (sigma A, sigma H),
      heterologous DNA hybridization (sigma D, sigma H), and immuno characterization of
      purified proteins (sigma A) from various clostridial species. Thus, the picture
      emerges that a fundamental similarity exists at the genetic level between the
      regulation of various cellular responses, in particular sporulation, in the
      genera Bacillus and Clostridium. The different induction patterns of sporulation
      in Bacillus spp. (nutrient starvation) and many clostridial species (cessation of
      growth or exposure to oxygen in the presence of excess nutrients) are most
      interestingly not reflected in the general regulatory features of this
      developmental process.

PMID- 7576772
TI  - Expression of heat shock genes in Clostridium acetobutylicum.
AB  - Characterization of the heat shock response in Clostridium acetobutylicum has
      indicated that at least 15 proteins are induced by a temperature upshift from 30
      to 42 degrees C. These so-called heat shock proteins include DnaK and GroEL, two
      highly conserved molecular chaperones. Several genes encoding heat shock proteins
      of C. acetobutylicum have been cloned and analysed. The dnaK operon includes the
      genes orfA (a heat shock gene with an unknown function), grpE, dnaK, and dnaJ;
      and the groE operon the genes groES and groEL. The hsp18 gene coding for a member
      of the small heat shock protein family constitutes a monocistronic operon.
      Interestingly, the heat shock response in this bacterium is regulated by a
      mechanism, which is obviously different from that found in Escherichia coli. So
      far, no evidence for a heat shock-specific sigma factor of the RNA polymerase in
      C. acetobutylicum has been found. In this bacterium, like in many Gram-positive
      and several Gram-negative bacteria, a conserved inverted repeat is located
      upstream of chaperone/chaperonin-encoding stress genes such as dnaK and groEL and
      may be implicated as a cis-acting regulatory site. The inverted repeat is not
      present in the promoter region of hsp18. Therefore, in C. acetobutylicum there
      are at least two classes of heat shock genes with respect to the type of
      regulation. Evidence has been found that a repressor is involved in the
      regulation of the heat shock response in C. acetobutylicum. However, this
      regulation seems to be independent of the inverted repeat motif, and the
      mechanism by which the inverted repeat motif mediates regulation remains to be
      elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576773
TI  - Chemotherapeutic tumour targeting using clostridial spores.
AB  - The toxicity associated with conventional cancer chemotherapy is primarily due to
      a lack of specificity for tumour cells. In contrast, intravenously injected
      clostridial spores exhibit a remarkable specificity for tumours. This is because,
      following their administration, clostridial spores become exclusively localised
      to, and germinate in, the hypoxic/necrotic tissue of tumours. This unique
      property could be exploited to deliver therapeutic agents to tumours. In
      particular, genetic engineering could be used to endow a suitable clostridial
      host with the capacity to produce an enzyme within the tumour which can
      metabolise a systemically introduced, non-toxic prodrug into a toxic metabolite.
      The feasibility of this strategy (clostridial-directed enzyme prodrug therapy,
      CDEPT) has been demonstrated by cloning the Escherichia coli B gene encoding
      nitroreductase (an enzyme which converts the prodrug CB1954 to a highly toxic
      bifunctional alkylating agent) into a clostridial expression vector and
      introducing the resultant plasmid into Clostridium beijerinckii (formerly C.
      acetobutylicum) NCIMB 8052. The gene was efficiently expressed, with recombinant
      nitroreductase representing 8% of the cell soluble protein. Following the
      intravenous injection of the recombinant spores into mice, tumour lysates have
      been shown, by Western blots, to contain the E. coli-derived enzyme.

PMID- 7576770
TI  - Regulation of nitrogen metabolism, starch utilisation and the beta-hbd-adh1 gene
      cluster in Clostridium acetobutylicum.
AB  - The successful genetic manipulation of Clostridium acetobutylicum for the
      increased production of solvents will depend on an understanding of gene
      structure and regulation in the bacterium. The glutamine synthetase (glnA) gene
      is regulated by antisense RNA, transcribed from a downstream promoter, in the
      opposite direction to the glnA gene. An open reading frame (ORF) was detected
      downstream of the glnA gene, which has sequence homology to response regulators
      with anti-termination activity and may be involved in sensing nitrogen
      conditions. The expression of the linked beta-hbd, adh1 and fixB genes was
      investigated throughout the bacterial growth cycle by RNA hybridisation
      techniques. The adh1 gene was independently expressed as a 2.4-kb transcript
      which peaked at 12 h, immediately prior to the solventogenic phase. The beta-hbd
      and fixB genes were transcribed throughout the acidogenic and solventogenic
      phases. A regulator gene, regA, which complements a Bacillus subtilis ccpA
      mutant, has been identified and sequenced from C. acetobutylicum P262. The regA
      gene repressed the degradation of starch by an uncharacterised C. acetobutylicum
      gene, and may therefore play a role in the utilisation of carbohydrate substrates
      in this organism.

PMID- 7576774
TI  - Current concepts of imaging in patients with pituitary/hypothalamic dysfunction.
AB  - MRI has value in differentiating the normal anatomy and abnormalities of the
      hypothalamic and pituitary regions. The hypothalamus and the pituitary gland are
      contiguous structures. They are functionally and physiologically inseparable. The
      hypothalamus functions primarily as an integrating mechanism for various
      autonomic and neuroendocrine activities, including temperature regulation, water
      balance, behavior, and appetite. The adenohypophysis of the pituitary gland
      contains at least five histologically distinct cell types responsible for
      hormonal secretion. The characteristic locations of these functional cell types
      correlate well with the common sites of various pituitary adenomas. MRI can
      visualize the pituitary gland and the hypothalamus noninvasively in healthy
      people and in patients with diverse diseases.

PMID- 7576775
TI  - Thyroid and parathyroid imaging.
AB  - This article reviews the current roles of imaging in the diagnosis of thyroid and
      parathyroid disorders, with an emphasis on ultrasound evaluation. Imaging of the
      thyroid and parathyroid can be performed with nuclear medicine, ultrasound, CT,
      and MRI. Indications for thyroid and parathyroid imaging studies have recently
      changed. The availability of experienced endocrine surgeons, as well as the
      development of accurate laboratory tests, fine-needle aspiration (FNA) biopsy,
      and high-resolution ultrasound, have dramatically influenced the evaluation of
      thyroid and parathyroid disease. In patients with thyroid nodular disease, a
      clinical examination by an experienced clinician with appropriate lab values and
      palpation-guided FNA is the current diagnostic protocol of choice. Ultrasound
      evaluation of high-risk patients and ultrasound-guided FNA both augment this
      protocol when necessary. In patients with diffuse thyroid glandular disease,
      radionuclide imaging and color Doppler sonography both can be used for
      evaluation. When preoperative imaging is clinically necessary, sonography or
      scintigraphy can be used for parathyroid adenoma localization in patients with
      primary hyperparathyroidism. The recent development of technetium-99m sestamibi
      as a parathyroid imaging agent has improved the sensitivity of scintigraphy for
      parathyroid adenoma localization. Ultrasound and radionuclide imaging have also
      become valuable imaging techniques for parathyroid localization in patients with
      recurrent or persistent hyperparathyroidism.

PMID- 7576776
TI  - Imaging assessment of pubertal disorders.

PMID- 7576779
TI  - Imaging of gastrointestinal neuroendocrine tumors.
AB  - Gastrointestinal neuroendocrine tumors are rare neoplasms that cause classic
      clinical syndromes because of the excess secretion of specific gastrointestinal
      hormones. The two most important tumors clinically are insulinomas and
      gastrinomas. The clinical management of patients with these disorders usually
      involves the localization and surgical removal of the responsible tumor. Many
      radiological techniques can be used for tumor localization, including
      preoperative and intraoperative ultrasound, endoscopic ultrasound, CT, MRI,
      radionuclide scanning, angiography, and venous sampling. However, there are
      conflicting claims as to the relative accuracy of these procedures, and many of
      these investigations are difficult to justify because of their high cost, degree
      of invasiveness, or lack of precise anatomic information that is obtained. If
      surgical resection of a neuroendocrine tumor is planned, intraoperative
      sonography should always be used to detect occult nonpalpable tumors and to
      discern the relationship of the tumor to vital adjacent pancreatic ductal
      anatomy. The choice of preoperative imaging is more controversial, and depends on
      the clinical problem, local expertise, and availability of imaging techniques.
      Sonography and contrast-enhanced helical CT are the most commonly used
      preoperative imaging methods, because of their relatively low cost and widespread
      availability. Radionuclide scanning with a somatostatin analogue, which is a
      relatively new procedure, may be valuable in patients with symptoms of tumor
      recurrence.

PMID- 7576777
TI  - Radiological evaluation of infertility.
AB  - With unwanted infertility on the rise, the radiologist is becoming increasingly
      involved both in the diagnosis and treatment of these patients. Assessment of the
      six most common factors causing infertility should be performed during the
      initial clinical evaluation. These six factors include the cervical factor,
      endometrial-uterine factor, tubal factor, ovarian factor, peritoneal factor, and
      male factor. Each of these groups will be discussed in detail with special
      attention to optimal methods of diagnosis. Hysterosalpingography and ultrasound
      play the major roles in evaluation; however, there is an important emerging role
      for newer techniques such as MRI and selective fallopian tube catheterization.

PMID- 7576778
TI  - Adrenal imaging.
AB  - CT is the imaging procedure of choice for detecting adrenal masses. In patients
      with biochemical evidence of an adrenal endocrine syndrome, CT can detect or
      exclude an adrenal mass in a high percentage of cases. Radionuclide scintigraphy
      is a useful adjunct in selected cases to characterize an adrenal mass as
      functional cortical (NP-59) or medullary (MIBG) tissue. In this article, the
      spectrum of adrenal imaging findings in patients with Cushing's syndrome, Conn's
      syndrome (primary aldosteronism), and pheochromocytoma is described and
      illustrated. In patients without an adrenal endocrine syndrome, an adrenal mass
      is detected on CT as an incidental finding or during a search for metastatic
      disease. Although pathognomonic findings of adrenal hemorrhage or myelolipoma are
      occasionally demonstrated, most adrenal masses have nonspecific morphological CT
      features. Differentiation of common benign adenomas from nonadenomatous adrenal
      masses, including metastases, remains an important clinical problem. This article
      reviews the current status, advantages, and limitations of the following methods
      to characterize an adrenal mass: (1) percutaneous adrenal biopsy, (2) NP-59
      scintigraphy, (3) unenhanced CT densitometry, and (4) opposed-phase chemical
      shift MRI.

PMID- 7576781
TI  - [Sucking behavior of normal full-term and low-risk preterm infants].
AB  - The sucking behavior of infants was analyzed by taking pictures using a
      fiberscope. The pictures were taken from inside an artificial nipple when a baby
      was sucking. The recording was carried out on babies of between 38 and 40 weeks
      gestational age. The subjects were 20 normal full term infants and 20 low-risk
      preterm infants. Individual differences were found, but it was possible to
      abstract the common components of the sucking behavior. The main components
      studied were the degree of adhesiveness of the lips to the breast for forming an
      airtight closure, the degree to which the tongue wraps the nipple, the width of
      the peristaltic tongue movements, and 6 other components. Each component was
      measured on a 3 point scale, where 1 is poor, 2 is good and 3 is excellent. The
      total score for each subject was determined by adding the scores for all nine
      components. The overall score for each infant indicates a level of individual
      sucking behavior. After the scale was compiled, the level of the sucking behavior
      of normal full term infants and that of low-risk preterm infants were assessed.
      The result showed significant discrepancies between the two groups. Low-risk
      preterm infants had lower overall scores than normal full term infants, and this
      difference was seen in all nine components.

PMID- 7576780
TI  - [Administration of a single oral high-dose of diazepam at bedtime as therapy for
      intractable seizures].
AB  - Recently the usage of diazepam as an anticonvulsant has been reduced. But, in
      this report, the effect of diazepam in the treatment of infantile spasms and
      intractable epilepsies were reported. Single high-dose oral administration of
      diazepam at bedtime was tried to the patients with intractable seizures. There
      were good responses to the therapy of partial seizures and infantile spasms
      basically escaping from hypsarhythmia. The therapeutic range of blood
      concentration was not decided, but probably the following values are necessary;
      over 200 nl/ml for partial seizures and over 300 ng/ml for infantile spasms 2
      hours after the administration. Plasma level of diazepam during the daytime was
      very low, but the seizures were controlled sufficiently.

PMID- 7576782
TI  - [Increased gamma delta T cells in peripheral blood of patients with severe
      neurologic impairment].
AB  - We examined peripheral gamma delta T cells in patients with severe neurologic
      impairment. The gamma delta T cells in these patients significantly increased as
      compared with those in healthy adults (P < 0.0001). These cells expressed the V
      gamma 9/V delta 2 phenotype which was reported to proliferate by infections. When
      patients with severe neurologic impairment and patients with Duchenne muscular
      dystrophy (DMD) were divided into frequent and non-frequent infectious groups,
      the gamma delta T cells increased significantly in the frequent infectious group
      of DMD (P < 0.005), but not significantly in the frequent infectious group of
      patients with severe neurologic impairment. These results indicated that the
      gamma delta T cells of patients with severe neurologic impairment increased in
      frequent infections and other factor(s).

PMID- 7576783
TI  - [Short somatosensory evoked potentials in patients with Fukuyama type congenital
      muscular dystrophy--a comparison with CT and MRI findings].
AB  - Seven patients with Fukuyama type congenital muscular dystrophy were studied. Low
      density areas (LDs) in the cerebral white matter on cranial CT were present in
      all 4 patients younger than 13 years of age and in 1 of 3 adult patients. LDs
      corresponded to low signals on T1 weighted MRI image and high signals on T2
      weighted MRI image. The follow-up MRI showed a decreased tendency of the abnormal
      signals in 2 patients. Short somatosensory evoked potentials (SSEPs) in two
      infants, aged 4 months and 8 months, showed absent or depressed N1 amplitudes and
      delayed interpeak latencies from P3 to N1. N1 amplitudes increased on follow-up
      studies. SSEPs of five patients, who were older than 2 years of age, showed
      normal N1-P3 latencies. Amplitude of N1 was low in 2 patients with LD. Since the
      absent or depressed amplitude and delayed latency of N1 improved with the
      decrease of abnormal signals on MRI, we considered that N1 abnormalities show
      delayed myelination.

PMID- 7576784
TI  - [Effect of the ketogenic diet for West syndrome into which early infantile
      epileptic encephalopathy with suppression-burst was evolved].
AB  - A male infant with early infantile epileptic encephalopathy (EIEE) was reported.
      Tonic spasms in series appeared since 1 month after birth and EEG showed a
      typical suppression-burst pattern. The patient was treated with a high-dose
      pyridoxal phosphate and thyrotropin-releasing hormone (TRH), but seizures were
      not controlled. ACTH was administered and the seizures disappeared transiently.
      The seizures reappeared during tapering ACTH and apparent cerebral shrinkage
      followed the ACTH therapy. Then, the patient who evolved into West syndrome was
      treated with ketogenic diet. The seizures disappeared immediately and EEG
      findings were improved. It is suggested that the ketogenic diet should be tried
      early for the treatment of EIEE.

PMID- 7576786
TI  - [A specific disorder of Kanji writing observed in a learning-disabled child-
      cognitive-psychological and neuropsychological analysis].
AB  - We reported a learning-disabled child who demonstrated a specific disorder of
      Kanji writing. A right-handed 13-year-old boy had showed no abnormality in
      general intelligence (VIQ114 and PIQ 100 in WISC-R), but could write only 35% of
      Kanji, which he should have learned six years before. It was necessary to develop
      a new test battery to detect the symptom which had not been detected using
      current existing test batteries. In cognitive-psychology, this patient had a
      retrieval disorder of graphic forms of Kanji. In addition, he showed a disorder
      in reproduction of complex graphic forms which he was asked to remember.
      Therefore, it is likely that he had a disorder for both Kanji and complex graphic
      forms, which is similar to the syndrome of pure agraphia of Kanji in adults.

PMID- 7576785
TI  - [A case of absence of the left internal carotid artery].
AB  - A case of absence of the left internal carotid artery with epilepsy was reported.
      Only a few cases of absence of the internal carotid artery with epilepsy in
      childhood have been reported in Japan. A flow void image of the cavernous sinus
      portion of the left internal carotid artery was not obtained on MRI. MR
      angiography and digital subtraction angiography also did not reveal the left
      internal carotid artery. On thin slice, axial CT scanning of the skull base, the
      right carotid canal was normally observed, but the left carotid canal was
      hypoplastic. It was suggested that the epileptic focus was in the right
      hemisphere, judging from the fast waves dominant over the right hemisphere on
      ictal EEG, and the hyperfusion in the right parietal and occipital lobes seen on
      99mTc-HMPAO SPECT one hour after the seizure.

PMID- 7576787
TI  - [Melatonin treatment for sleep-wake disorder--an experience for a severely mental
      retarded patient with blindness].

PMID- 7576788
TI  - [Exacerbation of complex partial seizures by carbamazepine in a child with
      frontal lobe epilepsy].

PMID- 7576789
TI  - [Analysis of genetic expression of FMR-1 gene in male patients with fragile X
      syndrome using RT-PCR method].

PMID- 7576790
TI  - [Neuropathological findings in a case of Hutchinson-Gilford progeria syndrome].

PMID- 7576791
TI  - The biology of hairy cell leukemia. A study of the practical aspects of
      interferon-treatment, its mechanism of action and on the pathogenesis of anemia.

PMID- 7576792
TI  - 2020 vision.

PMID- 7576793
TI  - Challenges in the provision of mental health services: some cautionary lessons
      from US experience.

PMID- 7576794
TI  - Assessment and possible control of endemic measles in urban Nigeria.
AB  - BACKGROUND: Measles remains as a serious problem of infancy and childhood in the
      developing world, despite the availability of a vaccine. Increasing urbanization
      is changing patterns of endemicity. METHODS: A survey of measles in an urban area
      of Nigeria, using a rapid assessment approach, was carried out to characterize
      measles in this community. RESULTS: An annual incidence rate of 11.8% among under
      fives was found, associated with an acute case fatality rate of 3.3%. This level
      of endemicity was two orders of magnitude greater than that suggested by official
      case reports. An endemic, rather than epidemic, pattern was found over the six
      month period of the study. Vaccine efficacy was estimated at 26%. Risk factor
      analyses showed the major risks for measles to be clinic attendance in the month
      preceding disease, households with more than one mother, and having under-five
      siblings. Measles itself was the principal risk factor for malnutrition and
      against survival. CONCLUSIONS: Improved understanding of measles epidemiology and
      risk factors are prerequisites for effective control. Possible strategies should
      include vertical vaccination efforts in addition to routine programmes.

PMID- 7576795
TI  - Infection control in general practice: results of a questionnaire survey.
AB  - BACKGROUND: Infection control is an important aspect of quality of care. General
      practitioners (GPs) have a high throughput of patients, some attending because of
      a communicable disease, others for investigations or minor operations. This
      situation provides an opportunity for the spread of infections. This study looked
      at the development of practice policies on infection control and the need for
      further information and guidelines. METHODS: A postal questionnaire was sent to
      117 practices in a single Family Health Services Authority. The questionnaire
      contained sections to be completed by a GP and a practice nurse in each surgery.
      RESULTS: A response rate of 74.5 per cent was obtained. Of the practices
      replying, 85 per cent did not have a written infection control policy.
      Sterilization of instruments was carried out in over 90 per cent of surgeries.
      Autoclaves were used in almost four-fifths of these practices; most did not have
      any written procedures covering their use. Few practices provided information on
      procedures for infected patients or staff. A third of practices did not have a
      needlestick policy, and sharps incidents were not recorded in 42 per cent of
      surgeries. Three-quarters of practices said that they would welcome guidelines on
      infection control. Half of the practice nurses thought that more training on
      infection control was required. CONCLUSIONS: The need for more training and the
      implications of the information from the study on the development and
      implementation of guidelines are discussed. Recommendations are made which aim to
      increase the awareness of this issue by means of guidelines and training focused
      on practice nurses.

PMID- 7576797
TI  - Psychological morbidity and the availability of assisted conception: a group
      comparison study.
AB  - BACKGROUND: Given its limited availability, it is worth while to explore the
      relationship between the non-availability of assisted conception and
      psychological morbidity among subfertile women, to see if those denied the
      procedure experience poorer health. METHODS: A non-randomized group comparison
      study was carried out in Bradford Health Authority, England. Sixty-six women who
      had reached the point at which assisted conception was deemed appropriate, but
      for whom such treatments were not available, were compared with 49 parous women,
      and 73 newly diagnosed subfertile women. The General Wellbeing Index (GWI) was
      used to measure their psychological wellbeing. RESULTS: Cases and subfertile
      controls have similar levels of wellbeing, whereas parous controls have
      significantly higher average levels than cases. This pattern is seen in the
      simple unadjusted comparison and also when adjustments are made for the
      distributions of age, life event score and social class. CONCLUSIONS: Subfertile
      women experience poorer psychological health than similar parous women.
      Subfertile women, for whom assisted conception is an appropriate but unavailable
      treatment option, appear to have similar psychological health to those who are
      being investigated and treated by other means.

PMID- 7576796
TI  - Health promotion in primary care: modelling the impact of intervention on
      coronary heart disease and stroke.
AB  - BACKGROUND: Since the health promotion programme for general practice was
      introduced in 1993, there has been some controversy about the potential
      effectiveness and likely cost-effectiveness of health promotion in general
      practice. The aim of this study was to generate a model to estimate the potential
      impact of the new general practice health promotion programme on coronary heart
      disease (CHD) and stroke, in terms of absolute reductions in mortality, in
      Cambridge Health Authority, a district with relatively low mortality rates for
      these two diseases. METHODS: A model to estimate the impact of the programme was
      derived from local data for risk factor prevalence in men and women aged 45-74;
      local death rates for CHD and stroke; and published data on the effectiveness of
      general practice health promotion. RESULTS: The expected number of deaths in the
      ten years following screening was estimated at 3203 deaths for CHD and 1075 for
      stroke. The model estimates a 12% reduction in CHD deaths and 17% fewer stroke
      deaths following the implementation of the programme. CONCLUSIONS: Even in areas
      where risk factor prevalence is low and death rates are low, the health promotion
      programme has the potential to have a moderate impact on CHD and stroke
      mortality. The cost-effectiveness of the programme, however, has yet to be
      established.

PMID- 7576798
TI  - Can national surveys be funded successfully from local NHS resources? Evidence
      from the Regional Study of Care for the Dying.
AB  - In the current economic climate, obtaining funding for large-scale national
      health services research surveys can be very difficult. In this paper we describe
      how the funding for a national survey, in which a random sample of 3696 bereaved
      relatives were interviewed, was obtained through collaboration with health
      regions and districts, and we consider the advantages and disadvantages of this
      approach. Although researchers considering using joint funding with the NHS may
      have to make compromises between ideal study design and what is feasible given
      local needs and the geographical spread of participating districts or NHS units,
      we conclude that collaboration can benefit both parties.

PMID- 7576799
TI  - Major chemical incidents--a response, the role of the Consultant in Communicable
      Disease Control and the case of need for a national surveillance-resource centre.
AB  - BACKGROUND: The aim of this study is to discuss the adequacy of current
      arrangements for dealing with major chemical incidents through the offices of the
      Consultant in Communicable Disease Control (CCDC). METHOD: This paper describes
      the public health response to an explosion at a chemical works which was followed
      by illnesses of unknown aetiology in emergency service workers and other people.
      An outline of the circumstances as they presented themselves and a description of
      the lessons learned from the management of this disaster are presented alongside
      an overview of the prevailing infrastructure of advice, support and training
      available to CsCDC. Key issues relevant to these areas are discussed. RESULTS: A
      total of 181 potential cases were notified to the investigating team, of whom 115
      had an illness possibly associated with the explosion. Of these, 93 suffered a
      gastrointestinal illness and 68 had so-called 'toxic' symptoms (eye, skin and
      bronchopulmonary irritation). Forty-six people had both sets of symptoms at the
      same time. CONCLUSIONS: Current arrangements dictate that public health
      physicians have a role in incidents such as this, whether they seek such a
      position or not. The specialty would do well to consider developing formal
      disaster training schemes for those likely to have to manage major incidents
      (usually the CCDC), and would benefit from the setting up of a chemical
      environmental incident surveillance-resource centre. Such a centre should have a
      remit for teaching and training, information support, incident recording,
      coordination of expert resources, and liaison between interested bodies both
      nationally and internationally.

PMID- 7576800
TI  - The changing face of community and institutional care for the elderly.
AB  - BACKGROUND: The NHS and Community Care Act 1990, implemented from 1 April 1993,
      was expected to alter profoundly the provision of domiciliary services to old
      people. This change needs to be compared with what would have happened if no
      action had taken place. We sought to identify trends in community and residential
      care before and after 1993 to facilitate this comparison. METHODS: Statistics
      were collated from diverse government publications and other authoritative
      sources. RESULTS: Between 1985 and 1993 there was a progressive contraction of
      public community and residential services, as well as hospital beds available to
      the elderly. The concomitant huge increase in places publicly funded in private
      old people's and nursing homes appears to have been little affected by the
      implementation of the NHS and Community Care Act. CONCLUSIONS: The NHS and
      Community Care Act has had little effect in curbing the institutionalization of
      old people, which has reached now the highest percentage this century at 7 per
      cent. A considerable expansion of community services would be required to return
      to the per capita provision of the early 1980s.

PMID- 7576801
TI  - Clinical and epidemiological pattern of long-stay in-patients: an opportunity for
      the provision of out-reach community services in Saudi Arabia.
AB  - BACKGROUND: The aim of the present study was to find out the clinical and
      epidemiological pattern of long-stay in-patients. METHODS: A cross-sectional
      survey of long-stay patients in Ministry of Health general hospitals was
      conducted during the period January-June 1993. A trained research team which
      consisted of a physician, a nurse, social workers and medical record officers
      completed a pre-designed data form and interviewed treating teams, patients and
      their relatives. The data form consisted of sociodemographic data of patients,
      their duration of stay, and their clinical, social and psychological
      characteristics. The doctors', patients', their relatives' perceptions and their
      preferences about the place of care (hospital or home) plus the geographical
      location of the hospitals involved were also recorded. RESULTS: Of the 1194
      patients, 55 per cent came from either the central or southern regions. Male
      patients represent 65.2 per cent and the elderly (> 60 years of age) 41.6 per
      cent. Multiple pathologies were found in 50.9 per cent and special signs and
      symptoms, e.g. incontinence, were found in 59 per cent. The medical team felt
      that 54.1 per cent of all patients did not need nursing or required only routine
      nursing care. Treating doctors thought that 16.2 per cent of patients did not
      need admission and that a further 54.8 per cent could be cared for in the
      patient's home. However, 47.5 per cent of patients preferred to stay in hospital,
      and 60.6 per cent of their relatives preferred them to remain in hospital.
      CONCLUSIONS: There is a need to plan for more cost-effective facilities for these
      patients. Any proposed health services will have to be culturally acceptable so
      as to encourage patients and relatives to utilize them.

PMID- 7576803
TI  - Health visitors' knowledge, attitudes and practices in childhood accident
      prevention.
AB  - BACKGROUND: The importance of the health visitor's role in childhood accident
      prevention has long been recognized, although previous work suggests that many
      health visitors are unsure of that role, feel inadequately prepared for it and
      recognize significant constraints on their accident prevention activity. The
      Health of the nation suggested that specific accident prevention activities
      should be undertaken by health visitors. This study aims to assess whether those
      activities are currently part of routine health visiting practice, as well as the
      attitudes towards accident prevention and knowledge of childhood accidental
      injury epidemiology. METHOD: A postal questionnaire survey covering knowledge,
      attitudes and practices in accident prevention as well as personal
      characteristics was sent to all health visitors in Nottinghamshire, using the
      community unit trusts' list of employees as the sampling frame. RESULTS: A
      response rate of 88.5 per cent was obtained. The majority of health visitors were
      aware that accidental injuries are the most common cause of death in childhood
      above the age of one year. The majority of health visitors were also aware of the
      types of accident most likely to be fatal, and aware of the risk factors for
      childhood accidental injuries. Many health visitors held positive attitudes
      towards all accident prevention activities covered in the questionnaire. There
      was a positive correlation between attitude and knowledge scores (p < 0.01).
      There were some discrepancies between attitudes and current practices,
      particularly in the areas of teaching first aid to parents' groups and lobbying
      or campaigning on local safety issues. CONCLUSIONS: Although many health visitors
      hold positive attitudes towards, and currently undertake many of the accident
      prevention activities suggested in the Health of the nation, there are areas
      where practice could be improved, such as giving advice about stockists of safety
      equipment including local loan schemes, undertaking first aid sessions in
      parents' groups and lobbying or campaigning on local safety issues.

PMID- 7576802
TI  - Strategies for sampling black and ethnic minority populations.
AB  - BACKGROUND: The objective of the study was to describe the design and sampling
      methods used to carry out face-to-face interviews with a sample of the black and
      ethnic minority population of the area. This study was conducted in the city of
      Bristol, England (part of Bristol and District Health Authority). METHODS: The
      sample was based on up to 1000 interviews with black Caribbean/African, South
      Asian and Far-East Asian residents. The design of the study focuses on the
      problems of definition of the appropriate group to sample and the various
      sampling techniques that were necessary to procure the interviews. RESULTS: A
      total of 574 interviews were carried out by bilingual interviewers matched for
      sex and ethnicity of the respondent, thereby allowing analysis that would be
      beneficial to the Health Authority in its planning and decision-making.
      CONCLUSIONS: The use of name spotting and 'snowball' sampling proved the most
      productive. The Electoral Register was preferred to the Family Health Services
      Authority lists. Interviewers must be carefully selected and adequately trained
      to work in this difficult area. The questionnaire must be culturally and
      linguistically acceptable across all the ethnic groups.

PMID- 7576804
TI  - A review of hospital discharge rates in a population around Camelford in North
      Cornwall up to the fifth anniversary of an episode of aluminium sulphate
      absorption.
AB  - BACKGROUND: The aim of this study was to assess the impact of the pollution
      caused by the aluminium sulphate emptied into the water at the Lowermoor
      Treatment Works on the standardized hospital discharge ratios in the Camelford
      area, Cornwall. METHOD: Comparisons were made between the Camelford area and
      other localities in Cornwall of standardized hospital discharge ratios up to five
      years following the pollution incident. The diagnoses of discharges were defined
      by ICD 9 code and grouped in chapters. The figures for Camelford were compared
      with those for Cornwall. RESULTS: Since the pollution incident, the standardized
      discharge ratio has increased in the Camelford area compared with Cornwall. No
      similar increase was observed in other localities of Cornwall. No one diagnosis
      was found to cause this increase. CONCLUSIONS: The pollution of the water to the
      people of Camelford has raised hospital discharges. Monitoring of hospital
      discharges will continue.

PMID- 7576805
TI  - Factors relating to smoking and pregnancy in the North Western Region.
AB  - BACKGROUND: One of the targets for the Health of the nation is to increase the
      proportion of women smokers who give up smoking at the start of their pregnancy,
      from a quarter to at least one-third, by the year 2000. This study uses a
      regional lifestyle survey to look at the characteristics of pregnant women who
      smoke. METHODS: The lifestyle survey was based on a structured questionnaire
      which was sent by post to a systematic random sample of 60,000 adults across the
      North Western Region. A total of 513 respondents were pregnant; of these, 150 (29
      per cent) reported that they smoked. The responses of pregnant smokers and non
      smokers were compared to identify differences in age, demographic and social
      characteristics, mental distress and attitudes to lifestyle variables. RESULTS:
      Women in the North Western Region who smoked tended not to give up during
      pregnancy, but they did tend to smoke less. Smokers were more likely to be under
      25 than non-smokers, less likely to be home-owners, and less likely to be living
      with a husband or partner. There was no difference in mental distress between
      smokers and ex-smokers, but they both experienced significantly greater mental
      distress than those who had never smoked. The difference between smokers and ex
      smokers was in their type of occupation, housing tenure and whether they were
      living with a partner, ex-smokers being much more similar to non-smokers.
      CONCLUSIONS: More work needs to be done to improve the design of smoking
      cessation programmes, to make them more culturally appropriate for pregnant women
      who appear to be socially disadvantaged, have poor housing and lack a stable
      relationship.

PMID- 7576806
TI  - Market testing specialist health promotion services--a test case for an
      imaginative public health presence in purchasing.
AB  - This paper focuses on the current pressure being imposed upon health promotion
      services in the 'North West' Region in the form of 'market testing'. It suggests
      that this is not only of concern to those services themselves, but may also act
      as a 'test case' for the examination of the range of competing perspectives that
      inform a purchasing function. The tensions between the views that respectively
      support or question the application of market values is thus examined in relation
      to the role of public health specialists within purchasing organizations. The
      paper concludes that although there is some potential to 'sharpen up' services,
      caution is required in avoiding unrestricted market values leading to superficial
      and fragmented health promotion provision. It is admitted that there are
      consequences relating to health promotion specialists. However, because of the
      close affinity between promotion and public health, failure to protect health
      promotion from the harshness of the market and ensure a broad-based approach will
      not only be a set-back for health promotion but will also harm the status of
      'public health perspectives' in the broader purchasing context.

PMID- 7576807
TI  - A survey of notified travel-associated infections: implications for travel health
      advice.
AB  - BACKGROUND: Travel-associated illness affects at least 25 per cent of UK
      residents who travel abroad each year. Notified cases form only a small
      proportion of the total community burden of disease but nevertheless represent a
      substantial workload for community infection control services. The aim of the
      study was to describe the incidence of notified travel-associated infectious
      illness, the extent and sources of travel health advice, and the nature of risk
      avoiding behaviour in that population. METHOD: A questionnaire survey was carried
      out of 190 consecutive notifications of food poisoning and malaria over a nine
      month period where travel abroad was an identifiable factor. RESULTS: The
      incidence of notified travel-associated food poisoning during the study period
      was 204 per million resident population per year. Thirteen per cent of
      respondents reported taking no precautions against food poisoning, and up to 75
      per cent of the cases could have taken better precautions. Only 36 per cent of
      cases recalled advice from their travel agent. Half the cases did not visit their
      general practitioner before travel (20 per cent of travellers to high-risk
      destinations). There was a strong association between receiving advice before
      travelling and risk-avoiding behaviour. The source of advice did not appear to
      affect the extent of precautions taken. The cases clearly expressed a need for
      additional written travel health information in the appropriate style and
      language for their ethnic group. Ethnic minority cases utilized official travel
      health advice to the same extent as the Caucasian cases. CONCLUSION: In this case
      series, 75 per cent of travellers did not take sufficient basic precautions
      against infection. There was a need to improve advice about simple precautions to
      avoid infection. General practice was the commonest source of advice for the
      travellers in this study. The apparently low level of advice from travel agents
      needs to be addressed in any local initiative to improve the health of
      travellers.

PMID- 7576809
TI  - Quarterly communicable disease review October to December 1994. From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 7576810
TI  - Determinants of breastfeeding in Salisbury and Durham.

PMID- 7576808
TI  - Sunburn and tanning in a British population.
AB  - BACKGROUND: The prevalence of sunburn and tanning, and associated attitudes were
      investigated in a national sample of adults in Great Britain. METHODS: A randomly
      selected cross-sectional sample of 2025 adults aged 16 or over living in England,
      Scotland and Wales were interviewed in October 1993 in the Office of Population
      Censuses and Surveys Omnibus Survey. RESULTS: The response rate was 77 per cent.
      Thirty-seven per cent reported at least one episode of sunburn in the past 12
      months, the highest frequencies being found in young age groups, in those with
      skin that tans poorly (p < 0.001), and in those who specifically tried to tan in
      this period (p < 0.001). Sunbathing was the most frequent activity associated
      with most severe episodes of sunburn, and occurred most frequently at the
      beginning of the summer, 46 per cent of episodes occurring abroad. Thirty-three
      per cent had tried to tan in the past 12 months, the proportion being highest in
      younger age groups and women (p < 0.001). Among those with severe sunburn more
      men (34 per cent) expected to burn when trying to tan than women (17 per cent).
      CONCLUSIONS: The results provide background information with which to develop and
      evaluate primary prevention initiatives for skin cancer. These should take into
      account the strong association between sunburn and the desire to tan,
      particularly in young adults and men.

PMID- 7576811
TI  - Is hospital the right place?

PMID- 7576812
TI  - Is hospital the right place?

PMID- 7576813
TI  - Communicable disease control in England; recommendations from an American.

PMID- 7576814
TI  - Activation of alpha-human tumour necrosis factor (TNF-alpha) by human monocytes
      (THP-1) exposed to 2-chloroethyl ethyl sulphide (H-MG).
AB  - Tumour necrosis factor (TNF) is a monokine produced by monocytes and macrophages
      in response to different stimuli. To determine whether vesicant agents such as
      half-mustard gas (H-MG; chemical structure: ClCH2CH2SCH2CH3) may induce the
      release of TNF-alpha in human monocytes (THP-1), ELISA experiments were conducted
      at different post exposure times. The results indicate that: (1) Significant
      increases in the TNF-alpha (pg mL-1) concentration were observed as a function of
      time when THP-1 cells were exposed to 100 microL of 2 M H-MG. A specific serine
      type protease inhibitor, N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), led
      to partial but significant inhibition of TNF activation. (2) Furthermore, this
      laboratory detected the generation of spin adducts of 2-methyl-2-nitrosopropane
      (MNP) having a resemblance to MNP-adducts generated from hydrogen atom
      abstraction of protein constituents. The EPR/Spin Trapping data indicate the
      trapping of by-products of protein degradation after exposure to H-MG. TNF-alpha
      may play a role as a biochemical marker for pathophysiological changes induced by
      H-MG or related agents.

PMID- 7576815
TI  - Glucocorticoid amelioration of nephrotoxicity: a study of cephaloridine
      methylprednisolone interaction in the rat.
AB  - Groups of ten male rats were treated with a high challenge dose of cephaloridine
      (CPH, 3750 mg kg-1), with methylprednisolone (MP, 100 mg kg-1) or with
      cephaloridine and methylprednisolone (CPH + MP) by single subcutaneous injection.
      A control group received the injection vehicles only. Urine was collected from
      all animals daily over 18-h collection periods, up to 96 h after treatment. Blood
      was collected at 24, 48, 72 and 96 h after treatment. At necropsy, kidneys were
      weighed, processed and examined histopathologically. Results show that
      methylprednisolone significantly ameliorated the nephrotoxicity of the challenge
      dose of cephaloridine. CPH-only treated rats had severe toxic nephrosis
      characterised by acute tubular necrosis, and elevated blood urea and creatinine.
      By contrast, the majority of CPH + MP treated rats had only a slight or moderate
      toxic nephrosis, and had lower blood urea and creatinine levels compared with
      rats treated with CPH only, indicating preservation of kidney function.
      Interestingly, rats treated with CPH + MP had higher urinary enzymes (alkaline
      phosphatase, lactate dehydrogenase, gamma glutamyltransferase and N-acetyl-beta
      glucosaminidase) as well as protein and glucose, compared with rats treated with
      CPH only. This is taken to indicate that rats treated with CPH only had such
      marked kidney damage and necrosis that the population of cells able to produce
      these marker enzymes was significantly and rapidly depleted, but the protection
      afforded by methylprednisolone allowed CPH + MP treated rats to sustain urinary
      enzyme output. Effects on urinary glucose and other parameters such as body
      weight and kidney weight demonstrate interactions between glucocorticoid
      pharmacology and cephaloridine nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576816
TI  - A review of drug-induced Leydig cell hyperplasia and neoplasia in the rat and
      some comparisons with man.
AB  - This paper describes control of normal Leydig cell function and testosterone
      production. The macroscopic and histopathological appearances of spontaneous
      Leydig cell hyperplasias and tumors (LCT) in the rat are reviewed together with
      their incidence and hormonal status. Drugs which induce LCTs in chronic studies
      are discussed and include busereline, carbamazepine, cimetidine, finasteride,
      flutamide, gemfibrozil, histrelin, hydralazine, indomethacin, isradipine,
      lactitol, leuprolide, metronidazole, mesulergine, nafarelin, norprolac and
      vidarabine. The known mechanisms of LCT induction in the rat are reviewed
      together with other possible etiological factors. The incidence, clinical picture
      and etiological factors of LCTs in man are also surveyed. Hormone production in
      Leydig cells and LCTs in rats and man are compared. Differences between the two
      species are considered, particularly with regard to Leydig cell control
      mechanisms. The paper concludes that drug-induced LCTs in rats are most probably
      not predictive for man and their occurrence has little relevance in human safety
      assessment.

PMID- 7576817
TI  - Concentration-response relationships for three nonsteroidal anti-inflammatory
      drugs in the rat intestine.
AB  - 1. The effect of diclofenac, piroxicam and (S+)-ibuprofen upon the rat intestine
      has been measured at constant drug plasma concentrations in the rat, using (51Cr)
      EDTA intestinal permeation as a measure of damage. Initially disposition studies
      after sc administration of the three NSAIDs were carried out. From these studies
      it was found that constant-rate iv infusions were necessary to maintain plasma
      concentrations of diclofenac and (S+)-ibuprofen. Administration of piroxicam by
      sc bolus gave relatively constant plasma concentrations, thus iv infusions were
      not necessary to obtain concentration-response data for this drug. Relative
      potency was found by comparing the concentration-response profiles of the three
      NSAIDs and the rank order of potency obtained was: diclofenac > piroxicam > (S+)
      ibuprofen. 2. The effect of mode of administration upon intestinal damage was
      also investigated using diclofenac. Intestinal permeability was measured in rats
      given diclofenac either by sc bolus or iv infusion and dose-response data
      compared. It was found that for the same dose, administration by sc bolus gave a
      higher degree of damage than by iv infusion.

PMID- 7576818
TI  - The generation of a human dermal equivalent to assess the potential contribution
      of human dermal fibroblasts to the sulphur mustard-induced vesication response.
AB  - 1. A human dermal equivalent (HDE) gel was constructed from rat tail tendon
      collagen (type 1) and human dermal fibroblasts (HFs). Histological studies
      revealed that the HFs within the HDE gel matrix assumed the shape of
      differentiated dermal fibroblasts and were metabolically viable as determined by
      the MTT assay. 2. The HDE system was developed to determine if viable,
      differentiated HFs have the potential to contribute to tissue damage by releasing
      the proteolytic enzyme elastase following exposure to sulphur mustard (HD).
      Elastase was measured, using the substrate suc-ala-ala-val-p-nitroanilide
      (SAAVNA), because of its association with various human pathological bullous skin
      diseases. An additional elastase substrate (suc-ala-ala-ala-p-nitroanilide;
      SAAANA) was also used. A miniaturised assay was employed to measure lactate
      dehydrogenase (LDH), a cytosolic enzyme released following damage to the cell
      membrane. 3. Elastase levels (measured with SAAVNA) increased to over 740% of
      those in control culture medium at 24 h after exposure of the HDE to HD (2 mM)
      and may therefore be part of the mechanism associated with dermo-epidermal
      separation and blistering in humans following exposure of skin to HD. LDH was
      released from the HDE after exposure to HD in a time dependent fashion,
      suggesting a steady leakage of cytosolic constituents after the initial exposure.
      4. The results suggest that differentiated human dermal fibroblasts have the
      potential to contribute to the development of the vesication response by
      releasing proteases such as elastase extracellularly after HD exposure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7576819
TI  - Further evidence that the blood/brain barrier impedes paraquat entry into the
      brain.
AB  - The distribution of the non-selective herbicide paraquat was examined in the
      brain following subcutaneous administration of 20 mg kg-1 paraquat ion containing
      [14C]paraquat to male adult rats in order to determine whether paraquat crosses
      the blood/brain barrier. Following administration, [14C]paraquat reached a
      maximal concentration in the brain (0.05% of administered dose) within the first
      hour and then rapidly disappeared from the brain. However, 24 h after
      administration of the herbicide, about 13% of the maximal recorded concentration
      of paraquat remained in the brain (1.6 nmol g-1 wet weight) and could not be
      removed by intracardiac perfusion. Using measurements of [14C]paraquat in
      dissected brain regions and using quantitative autoradiography we demonstrated an
      asymmetrical distribution in and around the brain at 30 min (maximal
      concentration) and 24 h after administration. Most of the paraquat was associated
      with five structures, two of which, the pineal gland and linings of the cerebral
      ventricles lie outside the blood/brain barrier whilst the remaining three brain
      areas, the anterior portion of the olfactory bulb, hypothalamus and area postrema
      do not have a blood/brain barrier. Overall, the distribution of [14C]paraquat in
      the brain 24 h after systemic administration was highly correlated to the blood
      volume. These data indicate that any remaining paraquat in the brain 24 h after
      systemic administration is associated with elements of the cerebro-circulatory
      system, such as the endothelial cells that make up the capillary network and that
      there is a limited entry of paraquat into brain regions without a blood/brain
      barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576821
TI  - Extrapyramidal manifestations complicating organophosphorus insecticide
      poisoning.
AB  - Six patients who developed extrapyramidal manifestations following poisoning with
      the organophosphorus (OP) insecticide fenthion are reported. The extrapyramidal
      features, in order of frequency, were dystonia, rest tremor, cog-wheel rigidity,
      and choreo-athetosis. The delay in onset of these signs, following poisoning,
      varied from 4 to 40 days, and they disappeared spontaneously in about 1 to 4
      weeks in those who survived. The human extrapyramidal system is rich in
      cholinergic neurons and acetylcholinesterase (AChE). Inhibition of AChE by
      fenthion, which has ready access to central neurons on account of its lipid
      solubility, is postulated as the mechanism underlying the extrapyramidal
      manifestations.

PMID- 7576820
TI  - Inter-subject variability in the metabolism of aluminium following intravenous
      injection as citrate.
AB  - 1. Six healthy male volunteers received intravenous injections of 26Al as
      citrate. Accelerator mass spectrometry and gamma-ray spectrometry were used to
      determine levels of the tracer in blood and excreta at times up to 5-6 d. 2.
      There was a rapid clearance from blood (mean 2% of injection remaining after 1 d)
      and major loss in urine (59% up to 1 d), but 27 +/- 7 (s.d.)% was retained in the
      body at 5 d. Faecal excretion was negligible (1% up to 5 d). 3. The mean results
      accord with the early metabolic pattern in the single subject of a previous, more
      extensive study, who had retained 4% of the injection after 3 y. Together, the
      two studies point to the likelihood of large inter-subject differences in the
      long-term accumulation of dietary aluminium by populations receiving a given
      level of daily intake.

PMID- 7576822
TI  - Differences in amiodarone, digoxin, flecainide and sotalol concentrations between
      antemortem serum and femoral postmortem blood.
AB  - 1. The concentrations of amiodarone/desethylamiodarone, digoxin, flecainide and
      sotalol were measured in serum collected immediately prior to death and in
      postmortem blood collected from the femoral vein and artery of an 18-year-old
      male with congenital heart disease who developed a fatal arrhythmia. 2. The
      concentrations of all four drugs in the sample collected during life were
      consistent with the dosage given and in the range accepted for normal therapy. 3.
      There were no differences in amiodarone/desethylamiodarone, flecainide and
      sotalol concentrations in arterial or venous postmortem blood. 4. The
      concentrations of desethylamiodarone, digoxin, flecainide and sotalol but not
      amiodarone, were higher in postmortem blood than in antemortem serum. The
      flecainide concentration was significantly greater than the upper limit
      associated with toxicity in life. Without knowledge of the true concentration
      measured in life, this apparently high, toxic concentration would have suggested
      that death could have resulted from arrhythmogenic/proarrhythmic effects of the
      drug in excess. 5. These results further demonstrate the hazards in interpreting
      postmortem blood concentrations following suspected drug intoxication.

PMID- 7576823
TI  - Ochratoxin A in human blood in relation to nephropathy in Tunisia.
AB  - The determination of ochratoxin A (OTA) in human blood in Tunisian populations is
      underway. The range of contamination is between 0.7 to 7.8 ng ml-1 for the
      general population and 12 to 55 ng ml-1 for people suffering from chronic renal
      failure. It appears that 21 to 64% of people suffering from nephropathy are OTA
      positive with a detection limit of 1ng ml-1. This situation prompted us to search
      for possible association of OTA contamination and nephropathy resembling Balkan
      endemic nephropathy. The classification of the ill population into chronic
      interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic
      vascular nephropathy (CVN) and others, indicated that the largest is the CIN
      group which is significantly different from the other groups, and from the
      control (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to
      59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml
      1) according to the designated region in Tunisia. The rural population seems to
      be more exposed to ochratoxins in Tunisia, as has been previously reported in the
      Balkans and Western Europe. Altogether, these results emphasise that in Tunisia
      an endemic ochratoxin-related nephropathy is probably occurring.

PMID- 7576824
TI  - Cross talk between the immune system and the nervous system in response to
      injury: implications for regeneration.

PMID- 7576825
TI  - Spectrum of in vivo hprt mutations in T lymphocytes from atomic bomb survivors.
      I. Sequence alterations in cDNA.

PMID- 7576826
TI  - Tyrosine kinase inhibition: an approach to drug development.

PMID- 7576827
TI  - Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B1
      carcinogenicity.

PMID- 7576829
TI  - Pesticide incidents reported to the Health and Safety Executive 1989/90- 1991/92.
AB  - 1. Data concerning pesticide incidents investigated by the Field Operations
      Division (FOD) of the Health and Safety Executive (HSE) in Great Britain have
      been collated for the three year period April 1989 to March 1992. Over this
      period the HSE investigated 613 incidents concerning pesticides: 338 related to
      general or environmental complaints not involving human poisoning and 275 were
      suspected poisoning incidents. 2. The two hundred and seventy-five suspected
      poisoning incidents were assessed by the Pesticide Incidents Appraisal Panel
      (PIAP) as 'confirmed', 'likely', 'unlikely', 'not confirmed', or that there were
      'insufficient data' to make an assessment. Assessed data are unavailable for
      eight incidents reported in 1989. 3. Four hundred and eighteen members of the
      public were involved in 202 assessed incidents and 79 workers were exposed in 65
      assessed incidents. Overall, 129 (48%) incidents were assessed as 'confirmed' or
      'likely', 121 (45%) as 'unlikely' or 'not confirmed' and in 17 (6%) there were
      'insufficient data' to form a judgement. Incidents occurring in an occupational
      setting were assessed as 'confirmed' or 'likely' more frequently (62%) than those
      involving members of the public (44%). 5. Thirty-six per cent of those involved
      in a 'confirmed' poisoning incident were working with a pesticide or were in
      close proximity to the operator; 41% were on private property adjacent to a field
      being sprayed and a further 23% involved those walking, cycling or jogging past a
      sprayed field.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576830
TI  - Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun
      poisoning.
AB  - 1. The effect of pyridostigmine on cardiorespiratory function after oxime +
      atropine injection was investigated in tabun poisoned guinea-pigs and without
      tabun poisoning. 2. The trachea, a carotid artery and jugular vein were
      cannulated in female urethane-anaesthetised Pirbright-white guinea-pigs. After
      baseline measurements the animals received pyridostigmine (0.05 mumol kg-1) and
      30 min later atropine (29.5 mumol kg-1) plus obidoxime, HI 6 or HLo 7 (30 or 100
      mumol kg-1) or tabun (1.85 mumol kg-1 = 5 x LD50) followed by oxime + atropine
      treatment (all i.v.). Erythrocyte, brain and diaphragm acetylcholinesterase
      (AChE) activity were determined. Similar groups without pretreatment were
      included for comparison. 3. Pyridostigmine aggravated the oxime + atropine
      induced hypotension and prevented the increase in heart rate but not the
      respiratory stimulation. The pyridostigmine inhibited AChE recovered only in the
      100 mumol kg-1 kg oxime groups at the end of the experiment. 4. In tabun
      poisoning, pyridostigmine reduced the oxime + atropine induced circulatory
      recovery and decreased the survival time and rate. It did not affect the
      therapeutic oxime + atropine effect on respiratory function. 5. These results
      suggest that pyridostigmine enhances oxime + atropine related circulatory
      depression which may be the reason for the reduced efficacy of oxime + atropine
      treatment in tabun poisoning. The possible mechanisms are discussed.

PMID- 7576831
TI  - Estimating the magnitude of carcinogenic effects in long-term animal studies.
AB  - Carcinogenicity studies seek to compare the incidence of tumours in animals
      exposed to the substance under investigation and animals used as controls. The
      conventional method of analysis is the Peto test, which assumes that tumours are
      either instantly fatal or have no effect on mortality and requires a judgement to
      be made regarding the lethality of each tumour. Such an assumption seems
      unrealistic and the judgement is often difficult to make and unreliable. The need
      for such a judgement and the assumption of extreme lethality can be removed by
      using parametric multi-state models. In this modelling approach the transition of
      animals between the states 'alive without a tumour', 'alive with a tumour' and
      'dead' is modelled mathematically. This paper compares the Peto test with tests
      based on two parametric multi-state models in terms of the sensitivity of the
      tests to detect carcinogenicity. The sensitivity, or power, is shown to be low
      for commonly used numbers of animals, depending chiefly on the expected total
      number of animals with tumours. The Omar and Whitehead multi-state model is found
      to be slightly more powerful than the Dewanji et al. model and at least as
      powerful as the Peto test. Provided the parametric assumptions are appropriate,
      this method thus gives a test that is more sensitive than the Peto test and
      enables estimation of tumour onset and mortality rates without the requirement of
      tumour lethality judgements.

PMID- 7576828
TI  - Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR
      mice.
AB  - 1. The present study was undertaken to examine the effects of H2-receptor
      antagonists including newly developed mifentidine derivatives, IY-80843 and IY
      80845, on cytochrome P450(P450) in vitro and in vivo. 2. Initially, 3
      methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver
      microsomes were prepared from male ICR mice to study in vitro effects of above
      chemicals on ethoxyresorufin O-deethylase(EROD), pentoxyresorufin O
      dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethylase(ERDM)
      activities, respectively. It was found that histamine, cimetidine and famotidine
      were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly
      inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845
      strongly inhibited PROD, EROD and ERDM activities. 3. Prolongation of
      hexobarbital-induced sleeping time was determined in male ICR mice to confirm in
      vitro inhibitory effects of mifentidine and its derivatives in vivo. It was
      observed that cimetidine, mifentidine, IY-80843 and IY-80845 caused dose
      dependent increases in the sleeping time, indicating the inhibition of P450
      responsible for hexobarbital metabolism. 4. It was concluded that mifentidine and
      its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is
      most inhibitory. 5. The present results indicate that mifentidine and its
      derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes.

PMID- 7576834
TI  - Central neurotoxicity induced by subchronic exposure to 2,4-pentanedione vapour.
AB  - 1. Male and female Fischer 344 rats were exposed to 2,4-pentanedione (2,4-PD)
      vapour acutely (4 h) at 1265 or 1811 ppm, or for 6 h day-1, 5 days a week for 14
      weeks to 0, 101, 307 or 650 ppm. 2. Mortality occurred during or within a few
      hours of the acute exposures (10% at 1265 ppm; 70% at 1811 ppm). No animal had
      gross or microscopic brain lesions. 3. All female rats (20) and 10 of 30 male
      rats exposed to 650 ppm 2,4-PD vapour died by the 38th study day (29 exposures);
      there were no subsequent male deaths. Twenty-five of the 30 animals that died,
      and seven of the 15 males that survived, had light microscopical evidence of
      degenerative lesions, principally within the caudate/putamen nuclei, nuclei of
      the cerebellar medulla, and vestibular nuclei. Less frequently involved, in
      animals that died, were various regions of the cerebral cortex. The early
      histopathological lesions, seen from the 16th study day (12 exposures) to the
      38th study day (28 exposures) were characterised by malacia. When present,
      lesions in male rats surviving the 14-weeks of 650 ppm 2, 4-PD exposure were
      characterised by malacia and gliosis. No peripheral nerve lesions were seen by
      light or transmission electron microscopy. 4. Neither mortality nor
      neuropathology were seen in rats subchronically exposed to 101 or 307 ppm, 2,4-PD
      vapour.

PMID- 7576832
TI  - Fenoverine-induced rhabdomyolysis.
AB  - Fenoverine is a spasmolytic drug that inhibits calcium channel currents. We
      describe the clinicopathologic findings in two patients with fenoverine-induced
      rhabdomyolysis, of whom one died. A transient left-bundle-branch block was
      observed in both patients. In one case, pre-existing hepatic dysfunction may have
      induced accumulation of the drug. Concurrent treatment by fibrates, as observed
      in the second patient, may have been a predisposing factor for fenoverine-induced
      rhabdomyolysis. The incidence of muscular complications of fenoverine therapy
      could be reduced by avoidance of prescription of the drug in patients with
      hepatopathy or those being treated with cholesterol-lowering agents. Physicians
      should be aware of life-threatening adverse effects of apparently innocuous
      drugs.

PMID- 7576833
TI  - Intrapleural administration of vitreous high duty ceramic fibres and heated
      devitrified ceramic fibres does not give rise to pleural mesothelioma in rats.
AB  - In order to determine whether they are potentially carcinogenic to the pleural
      mesothelium, three samples of ceramic fibre have been administered to rats by the
      intrapleural route. These samples were a high-duty grade refractory ceramic fibre
      (manufactured by Thermal Ceramics Ltd) in the as-manufactured vitreous state and
      two devitrified samples produced by heating the same fibre for 2 weeks at 1200
      degrees C and for two weeks at 1400 degrees C. The mean lifespans of the groups
      of rats treated with vitrified and devitrified ceramic fibres were not
      significantly different from that of the control rats. In these studies none of
      the treated or control rats developed pleural mesothelioma, making it unlikely
      that ceramic fibres of this type, whether vitreous or devitrified, are
      potentially carcinogenic to the pleural mesothelium.

PMID- 7576835
TI  - Comparison of toxicity induced by T-2 toxin on human and rat granulo-monocytic
      progenitors with an in vitro model.
AB  - T-2 toxin is a trichothecene mycotoxin produced by various species of fungi.
      Trichothecenes are known as major contaminants of cereals and their derivatives.
      In man as well as in animals, T-2 toxin has been shown to induce alimentary
      intoxication and, among others, haematological symptoms. Granulo-monocytic
      progenitors from human umbilical cord blood on the one hand and granulo-monocytic
      progenitors from rat bone marrow on the other, were cultured in the presence of T
      2 toxin (from 10(-7) to 10(-10) M) for 14 days. A study of concentration and
      effect relationships showed a strong and rapid effect of T-2 toxin on rat colony
      forming unit-granulocyte and macrophage (CFU-GM) between 5 x 10(-9) M and 10(-9)
      M. On the other hand, human CFU-GM were able to grow in the presence of the same
      T-2 toxin concentrations. IC50 were determined on day 7, 10 and 14. They were,
      respectively, 1.6 x 10(-9) M; 3.6 x 10(-9) M; 1.4 x 10(-9) M for human cells, and
      2.2 x 10(-9) M; 3.3 x 10(-9) M; 2.6 x 10(-9) M for rat cells. The present study
      was prompted by the need to define precisely the cytotoxic and inhibitory T-2
      toxin concentrations for rat and human CFU-GM. It is particularly relevant for
      the investigation of cellular T-2 toxin targets and in order to elucidate the
      mechanism of trichothecene haematotoxicity.

PMID- 7576836
TI  - Metabolites beat adducts and monitors.

PMID- 7576838
TI  - Promoting apoptosis.

PMID- 7576837
TI  - A possible relationship between N-acetyltransferase and folate metabolism.

PMID- 7576839
TI  - Peroxisomes without catalase: more evidence for the active oxygen hypothesis?

PMID- 7576840
TI  - Diphtheria revisited.

PMID- 7576841
TI  - Aspirin and acute myocardial infarction: clarifying the message.

PMID- 7576842
TI  - Family practice in the United States of America--a new dawn?

PMID- 7576843
TI  - Use of general practitioner beds in Leicestershire community hospitals.
AB  - BACKGROUND: The shift in care from secondary to primary services is likely to
      place greater demands on community hospitals. Before changes in the provision of
      community hospitals can occur, baseline data are needed, outlining their current
      use. AIM: A study was undertaken to obtain baseline data describing the use of
      general practitioner beds in Leicestershire community hospitals. METHOD: A three
      month prospective, observational study was carried out between February and May
      1992 using data from a questionnaire completed by nurses and general
      practitioners and from patient hospital records. Study patients comprised all
      patients admitted to general practitioner beds in all eight Leicestershire
      community hospitals. RESULTS: A 100% questionnaire response rate was obtained
      giving data on 685 hospital admissions. Around 70% of admissions were of patients
      aged 75 years and over. Of admissions, 35% were for acute care, 31% for respite
      care, 22% for rehabilitation, 7% for terminal/palliative care and 5% for other
      reasons. Fifteen per cent of patients had been transferred from a consultant bed.
      Of those not transferred, 91% were admitted by their usual general practitioner
      or practice partner and for 96% of these patients this was the general
      practitioner's first choice for care. There was significant variation in both the
      age mix and care category mix of patients between individual hospitals. Medical
      deterioration in an underlying condition and family pressure on the general
      practitioner or carers' inability to cope each contributed to around half of all
      admissions. Of all admissions, 38% lived alone, and 18% of carers were disabled.
      Incontinence was reported for 35% of patients, and 26% of all patients were of a
      high nursing dependency. There was low utilization of community services before
      admission and 33% received none. There was variation between individual hospitals
      in use of local and district general hospital investigations, specialist referral
      and types of therapy. Of 685 admissions 11% died during their stay. Of those
      discharged, 76% went to their own or a relative's home, 10% to a residential or
      nursing home and 9% were transferred to an acute bed. Nine percent of discharges
      were postponed and 10% were brought forward. On discharge to non-residential
      care, 26% of patients received no community services. CONCLUSION: Shifting
      resources from secondary to primary care is a priority for purchasers. Both the
      introduction of the National Health Service and community care act 1990, and
      acute units having increasing incentives for earlier discharge, are likely to
      place greater demands on community hospital beds. Not all general practitioners
      have the option of community hospital beds. Before access to general practitioner
      beds can be broadened, existing beds should be used appropriately and shown to be
      cost-effective. Purchasers therefore require criteria for the appropriateness of
      admissions to general practitioner beds, and the results of a general
      practitioner bed cost-benefit analysis.

PMID- 7576844
TI  - Membership of the Royal College of General Practitioners by assessment: attitudes
      of members and non-members in one faculty area.
AB  - BACKGROUND: Fewer than half of the principals in general practice in the United
      Kingdom are members of the Royal College of General Practitioners. As the
      membership examination is closely linked to the endpoint of vocational training,
      a case can be made for another method of entry to the RCGP for established
      principals. Such a method could be membership by assessment. AIM: A study was
      undertaken to examine the attitudes of existing members and fellows of the RCGP
      to membership by assessment and to determine whether there was any demand from
      general practitioner principals who were not RCGP members to join by this route.
      METHOD: One questionnaire was sent to all RCGP members and fellows in the Vale of
      Trent faculty area and another questionnaire was sent to those principals in
      general practice in the Vale of Trent faculty area who were not RCGP members.
      RESULTS: In total, 396 (83%) of the 480 RCGP members and fellows responded, as
      did 543 (81%) of the 671 non-members in the faculty area. When asked if they were
      in favour of the concept of membership by assessment, 245 of the members and
      fellows replied yes (62%) and 138 replied no (35%). Of the non-members, 91 (17%)
      ahd previously been members of the RCGP; the main reason given by these general
      practitioners for relinquishing membership was that the annual subscription was
      too high (65% of 91 general practitioners). When the 451 general practitioners
      who had never been members were asked if they would be interested in joining the
      RCGP by an assessment method, 271 replied positively (60%). CONCLUSION: There was
      widespread support from the members and fellows of the Vale of Trent faculty of
      the RCGP for the concept of membership by assessment. Principals in general
      practice in this area who had never been members of the RCGP showed a high degree
      of interest in joining by this method. Despite the caveats that must be applied,
      for example, to ensure that the standards are set appropriately, these results
      indicate that membership by assessment should be explored by the RCGP, and indeed
      a working party on the meaning of membership of the RCGP has been convened.

PMID- 7576845
TI  - Women's knowledge of taking oral contraceptive pills correctly and of emergency
      contraception: effect of providing information leaflets in general practice.
AB  - BACKGROUND: About one third of all pregnancies are unplanned and 20% of all
      pregnancies end in abortion. More than 170,000 legal abortions are performed in
      the United Kingdom annually. Nearly all general practitioners provide
      contraceptive advice; the most commonly used form of reversible contraception is
      the oral contraceptive pill. AIM: The aim of this study was to determine factors
      associated with women's knowledge of taking the contraceptive pill correctly and
      of emergency contraception, and to investigate if their knowledge could be
      improved in general practice by providing women with Family Planning Association
      information leaflets. METHOD: An uncontrolled intervention study was performed in
      one rural and one urban English general practice, using a self-completion
      questionnaire that was initially administered to women attending their general
      practitioner for oral contraception over six months from 1 October 1992. The
      questionnaire asked for: sociodemographic information; knowledge of how late
      women can be taking an oral contraceptive pill and still be protected against
      unplanned pregnancy; for how many days after being late with a pill they need to
      use other precautions; sources and methods of emergency contraception; and for
      how long the methods are effective after the primary contraceptive failure. After
      completing the questionnaire women were given two leaflets: one about how to take
      their prescribed contraceptive pill correctly and one about emergency
      contraception. Three to 12 months later the same questionnaire was administered
      in the same manner. RESULTS: Of 449 women completing the first questionnaire, 233
      (52%) completed the second questionnaire. Initially 71% of 406 women taking an
      oestrogen/progestogen combined pill knew about the '12-hour rule' and 17% knew
      about the 'seven-day rule'; giving women information about the pill they were
      taking increased the extent of knowledge about these rules among 212 respondents
      to 82% (P < 0.01) and to 25% (P < 0.05), respectively. The proportion of
      respondents who knew that they could obtain emergency contraception from their
      own general practitioner, from any general practitioner and from family planning
      clinics all increased after they had received the leaflets (from 84% to 92%, from
      34% to 47% and from 82% to 90%, respectively, all P < 0.01). There were
      significant improvements in the proportion of women knowing the duration of
      effectiveness of emergency contraception. However, after receiving the leaflet on
      emergency contraception the majority of women still did not know for how long
      after unprotected intercourse the high-dose combined pill and the intrauterine
      contraceptive device were effective (80% and 93% of 233 women, respectively).
      Improvements in knowledge depended upon women's social class, previous use of
      emergency contraception and with which practice they were registered. CONCLUSION:
      Providing women with leaflets about taking the contraceptive pill correctly and
      about emergency contraception appears to improve significantly their extent of
      such knowledge. If such practice was adopted elsewhere this increased knowledge
      might reduce the number of unplanned pregnancies in the UK. The effect of general
      practitioners personally providing such leaflets, with or without verbal
      instruction, warrants further study.

PMID- 7576846
TI  - Practice nurses' workload and consultation patterns.
AB  - BACKGROUND: There are calls for the role of the practice nurse to be developed
      and extended. Before areas for further training and education can be identified,
      baseline data are needed on practice nurses' current activity and workload. AIM:
      A study was undertaken to analyse the activity of practice nurses in two large
      inner city general practices and to assess the skills mix of the nursing staff
      required to meet the needs of the practices. METHOD: The study practices had a
      combined list of 26,000 patients, 80% of patients attracting a deprivation
      allowance. Each practice employed three practice nurses. A nurse activity index
      with 45 codes was constructed to describe patient-nurse consultations. Activity
      codes were categorized into traditional treatment tasks, extended role tasks or
      diagnosis and management tasks. For eight months, practice nurses in practices Y
      and Z recorded activity index codes for each patient consultation. Practice Y
      also recorded the source of referral and the age and sex of the patient. RESULTS:
      There were 13,898 practice nurse consultations during the study period,
      equivalent to an annual nurse consultation rate of 0.8 per patient. Compared with
      the practice population as a whole, the patients attending the practice nurses in
      practice Y were older (mean age 43 years versus 37 years, P < 0.001). Those
      attending the practice nurses in practice Y were also more likely to be female
      (61% of consultations were with female patients compared with 50% of the practice
      population as a whole, P < 0.001). In practice Y, patients referred themselves to
      the practice nurse in 42% of consultations, 32% were follow-up consultations and
      in 25% of cases the patient had been referred by a doctor. The most common
      reasons for nurse consultation were blood tests (15% of procedures in practice Y
      and 18% in practice Z) and dressings (13% in both practices). Most procedures in
      practices Y and Z were in the traditional treatment category (61%), 26% were in
      the extended role category and 9% in the diagnosis and management category (3%
      coded 'other', 1% uncoded). Between practices, the greatest difference in
      recorded procedures was for asthma check ups (7% of procedures in practice Y
      compared with 2% in practice Z). CONCLUSION: This study describes the workload of
      practice nurses in two inner city practices over eight months. Other practices
      could use the activity index to make comparisons over time and between practices.
      Up to 60% of nurses' work in the study practices could be done by a nurse without
      extended training and up to 30% could be done by a health care assistant, but
      with some loss of quality. It is suggested that half the nursing hours available
      to a practice should be offered by a nurse with extended training in order to
      undertake and develop extended role tasks and diagnosis and management tasks.

PMID- 7576847
TI  - How complete is influenza immunization coverage? A study in 75 nursing and
      residential homes for elderly people.
AB  - BACKGROUND: Elderly people in residential accommodation are particularly
      susceptible to outbreaks of influenza. Up to 70% of residents can become ill and
      many will develop complications or die. Immunization can prevent such outbreaks
      and is cost-effective. AIM: A study was undertaken to measure influenza
      immunization coverage in residential accommodation for elderly people and to
      identify factors that might influence uptake. METHOD: In March 1992, a
      questionnaire survey was conducted of all 113 registered nursing and residential
      homes for elderly people, in South Glamorgan. It asked about the demographic
      characteristics of people resident on 1 October 1991, their influenza
      immunization history and the homes' arrangements for administering immunizations.
      RESULTS: Questionnaires were returned by respondents from 75 homes (66%). Mean
      influenza vaccine uptake was 67%. Uptake was higher in nursing homes (mean of 82%
      in eight nursing homes) than in homes registered as both nursing and residential
      homes (mean of 76% in six homes) or in residential homes (mean of 65% in 61
      homes). Nearly all of those immunized (94%) had been immunized by the end of
      November 1991. Residents who were reported to have underlying disease that
      increased their risk of complications if they contracted influenza were no more
      likely to have been immunized than those without risk factors. Immunization
      coverage varied considerably both between homes and between general practices.
      Most general practices in South Glamorgan had several elderly people in
      residential accommodation on their list, but only nine out of 64 practices had
      immunized all the elderly residents on their list and 12 practices had immunized
      fewer than half. Routine recording of immunization status in nursing and
      residential homes was variable, often as a consequence of poor communication
      between the primary health care team and staff at the home. Even where recorded,
      retrieval of the data was sometimes a problem. CONCLUSION: Influenza immunization
      coverage could be improved if general practices held a case register of all at
      risk patients including elderly residents, and if nursing and residential homes
      were encouraged to keep better immunization records. These measures would
      facilitate year-on-year monitoring of influenza immunization coverage and the
      targeting of homes with low immunization coverage.

PMID- 7576849
TI  - Bereavement: a protocol for primary care.
AB  - Bereavement is experiencing a loss, particularly of a loved one, which leads to a
      natural cycle of grief that has recognized psychological stages. Even though
      bereavement does not fit the criteria for the biomedical model of disease, it is
      a medical problem as there is a resultant morbidity and increased mortality
      associated with the surviving intimates. A bereavement protocol, which could
      minimize the effects of bereavement, is proposed for organized care by the
      primary health care team in this neglected area for health promotion.

PMID- 7576851
TI  - Depression screening instrument.

PMID- 7576848
TI  - Addressing the patient's agenda in the reorganization of antenatal and infant
      health care: experience in one general practice.
AB  - BACKGROUND: Antenatal care is outdated and largely unevaluated. The study
      practice is committed to involving patients in their own health care. It was
      decided to use the views of patients to guide a review of antenatal and infant
      health services. AIM: The study, carried out in 1993, was designed to find out
      what patients' priorities were, and what they thought were the strengths and
      weaknesses in the organization and delivery of antenatal and infant health care.
      METHOD: A total of 52 women attending antenatal appointments were interviewed at
      the practice using an interview topic guide within a qualitative research
      framework. Fourteen parents attending a day centre with their under five-year
      olds participated in two focus groups. The findings of the interviews and focus
      group discussions were compared. RESULTS: The interviews revealed a high level of
      satisfaction with midwife care, although some changes in the organization of
      antenatal bookings and classes were indicated. Parents expected to be seen
      switfly at home or at the surgery when their infant was ill, and these high
      expectations were not always met. There was some degree of confusion and
      frustration over the role of the health visitor. The views expressed in the focus
      groups were broadly similar to those expressed in the interviews. CONCLUSION: The
      findings suggested that there was considerable potential for developing the role
      of both the midwife and the health visitor, and integrating their work more
      closely in the primary health care team. Examples are given of how these findings
      have altered the organization and delivery of antenatal and infant health care in
      the practice. The study showed that finding out and acting upon the views of
      patients is a practical way forward in the reshaping of services.

PMID- 7576850
TI  - Primary care and the maelstrom of health care reform in the United States of
      America.
AB  - Recent reform in the National Health Service has moved general practice towards a
      more intense market and competition structure. Meanwhile in the United States of
      America there has been an attempt to modify the free enterprise approach to
      medical care towards a more socially responsive system. This discussion paper
      provides a family doctor's perspective of primary care and the maelstrom of
      health care reform in the USA. The cultural, economic and organizational issues
      underlying the need for reform are considered in turn, and the current situation
      with regard to health care provision, medical research, medical education and
      primary care are outlined. General practitioners in the United Kingdom would do
      well to pay attention to the effects of market reform occurring in general
      practice among their American counterparts.

PMID- 7576852
TI  - Paracetamol in childhood illness.

PMID- 7576853
TI  - Outcome measure for parkinsons disease.

PMID- 7576854
TI  - Clinician involvement in commissioning.

PMID- 7576855
TI  - Facilitation projects.

PMID- 7576856
TI  - Research and development in primary care.

PMID- 7576857
TI  - Records, law and paternalism.

PMID- 7576858
TI  - Audit in summative assessment.

PMID- 7576859
TI  - Preventing skin cancer.

PMID- 7576861
TI  - Warfarin in stroke prevention.

PMID- 7576860
TI  - Videotaped consultations.

PMID- 7576862
TI  - Acute myocardial infarction.

PMID- 7576863
TI  - Burnout.

PMID- 7576866
TI  - Apoptosis in the nervous system: morphological features, methods, pathology, and
      prevention.
AB  - For nearly 70 years apoptosis has been known to be a form of cell death distinct
      from necrosis as well as an important regressive event during the normal
      development of the nervous system. For example, in the chick, mouse, rat and
      human approximately 50% of postmitotic neurons die naturally during embryonic or
      fetal development. It is generally accepted that neurons die during this period
      by apoptosis. After the period of naturally occurring cell death, the surviving
      neurons may undergo degeneration and death due to injury or disease later either
      during development or in adulthood. Recently, apoptosis has been suggested to be
      involved in the abnormal neuronal death that occurs following axonal injury or in
      neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's.
      Although little is known about the etiology of these diseases, progress is
      steadily being made toward understanding their underlying mechanisms. For
      diseases of spinal motoneurons, during the past two years gene mutations have
      been identified in patients with familial amyotrophic lateral sclerosis or spinal
      muscular atrophy. Furthermore, a number of in vitro, in vivo, and mutant animal
      models have been developed in order to study the factors which control motoneuron
      survival and/or death. Here, we review the morphological differences between
      necrotic and apoptotic cell death and some of the methods used to differentiate
      the two pathways. We also discuss motoneuron cell death during development,
      following injury and in disease, and its prevention by different agents,
      including neurotrophic factors.

PMID- 7576865
TI  - Apoptosis: The history and trends of its studies.
AB  - Recent molecular studies have revealed genes which regulate cell death,
      especially apoptosis, or programmed cell death occurring in organogenesis during
      fetal life, for the maintenance of cell numbers in the body by balancing cell
      production with cell death, and in tumor cell turnover. As has been suggested,
      however, cell death is not a single entity, but is heterogeneous in morphological
      and metabolic mechanisms, circumstances of initiation and biological significance
      (Wyllie, 1981); it is at present difficult to understand the entire cascade of
      intracellular metabolism concerning apoptosis. The present review focuses on the
      description of precise morphological features characteristic of apoptosis with
      those of necrosis, particularly inward and outward blebbings of the cell membrane
      causing cell shrinkage. Special reference is given to inward blebbing, an event
      which has been shown in various physiological and pathological apoptotic cells.
      In this process, the blebs form numerous clear vesicles in the cytoplasm, which
      are degraded together with parts of the cytoplasm by autophagolysosomes. Analysis
      of the processes of the death of cells and the determination of whether it is
      apoptotic or necrotic in nature is important when considering the fact that the
      hindrance of apoptosis in embryogenesis may cause congenital disorders, whereas
      its prevention in pathological diseases may open the way to new therapies.

PMID- 7576867
TI  - The involvement of macrophages and lymphocytes in the apoptosis of enterocytes.
AB  - Epithelial cells of the gut are characterized by rapid, constant cell renewal.
      The death of epithelial cells at the villus tips occurs so regularly that it must
      be regarded as a well-controlled cell death, designated as apoptosis. However,
      only limited information has been available on the mechanism of this phenomenon,
      including the disposal of the effete cells. In the small intestine of the guinea
      pig and monkey, macrophages are densely aggregated at the lamina propria of the
      villus tips and vigorously engaged in the phagocytosis of effete epithelial
      cells. Intraepithelial lymphocytes possessing cytoplasmic granules, possibly
      intense in cytotoxicity, are topographically associated with the dying
      enterocytes, suggesting lymphocyte-mediated killing. After the engulfing of
      apoptotic enterocytes is left within the epithelium, maintaining the epithelial
      barrier until it is pinched off by the pushing of surrounding enterocytes. In the
      rat and mouse, on the other hand, effete enterocytes are exfoliated as a whole
      from the villus tips into the gut lumen. Macrophages, also numerous at the villus
      tips in these species, are less intense in phagocytotic activity. At the shoulder
      region of the villus, subepithelial macrophages extend thick processes deep into
      the epithelium; the processes appear to push out some enterocytes with typical
      apoptotic signs into the gut lumen. Lamina propria macrophages in the rat and
      mouse do not engulf enterocytes, but are believed to be involved in the induction
      of their apoptosis. The species difference in the mechanism of the apoptosis of
      enterocytes provides clues for understanding apoptosis.

PMID- 7576864
TI  - GPs' low morale.

PMID- 7576868
TI  - Differential staining of DNA strand breaks in dying cells by non-radioactive in
      situ nick translation.
AB  - Various lines of evidence indicate the involvement of DNA strand breaks (DSB) in
      the regulation of physiological states of cells, especially in cell death.
      Currently, cell death is divided into two categories, apoptosis and necrosis. As
      lysosomal integrity is maintained in apoptosis, while disrupted in necrosis, it
      is possible to assume that necrotic chromatin is exposed to digestion by various
      lysosomal enzymes. We have therefore investigated whether apoptotic DSB and
      necrotic DSB can be discriminated by in situ nick translation (INT) under various
      conditions of protease pretreatment. Used models of apoptosis and necrosis were
      the rat thymus with an intraperitoneal injection of hydrocortisone (10 mg/100 g
      body weight (b.w.)) and rat liver with an intraperitoneal injection of CCl4 (100
      microliters/g b.w.), respectively. As results, we found that necrotic DSB was
      readily detected by INT without protein digestion, whereas apoptotic ones were
      not. These results indicate that the environment around DSB and/or the nature of
      DSB in apoptosis differs from that of necrosis, and that INT is a convenient
      molecular histochemical tool to discriminate both types of cell death in frozen
      sections.

PMID- 7576869
TI  - The ultrastructure, kinetics and intralobular distribution of apoptotic
      hepatocytes after portal branch ligation with special reference to their
      relationship to necrotic hepatocytes.
AB  - Apoptosis was originally defined as shrinkage necrosis, as a distinct mode of
      cellular death from coagulative necrosis in the rat liver lobes after portal
      branch ligation. To reveal the functional role of the apoptosis of hepatocytes in
      the volume reduction and recovery of normal hepatic architecture in portal
      deprived liver lobes, we ligated the portal vein branch supplying the left and
      median liver lobes in Wistar rats. The liver lobes were perfusion-fixed with
      glutaraldehyde solution via the proximal site of the ligated portion of the
      portal vein on Days 1, 2, 4, 7 and 14 after operation and examined light and
      electron microscopically. On Day 2 after ligation, massive necrosis of
      hepatocytes occurred in the central to intermediate zones of the liver lobule,
      and apoptotic hepatocytes were observed in the boundary region between necrotic
      and normal areas. Such necrotic area-associated apoptosis of hepatocytes was most
      frequent on Day 2, declining thereafter. The sequential changes of the cell
      organelles in apoptotic hepatocytes were distinct from those in necrotic
      hepatocytes. On Day 7, when necrotic areas had almost disappeared the apoptosis
      of hepatocytes occurred mostly between intact hepatocytes in the "combined
      hepatic cell cords" which included no obvious sinusoidal lumen between hepatic
      cell cords. Such necrotic area-nonassociated apoptosis began to increase in
      frequency on Day 4, reached a peak on Day 7 and was gone by Day 14, when normal
      hepatic architecture was recovered. The present study suggests that both necrotic
      area-associated and non-associated apoptosis of hepatocytes may be induced by
      mild ischemia and contribute in part to the volume reduction of ligated liver
      lobes. It further reveals that the necrotic area-non-associated apoptosis of
      hepatocytes plays a role in reconstructing the architecture of hepatic cell cords
      after necrotic hepatocytes have undergone dissolution in the liver lobule.

PMID- 7576870
TI  - Apoptotic cells in the human endometrium and placental villi: pitfalls in
      applying the TUNEL method.
AB  - Apoptotic cells were histochemically demonstrated by the TdT-mediated
      biotinylated dUTP nick end-labeling (TUNEL) method in formalin-fixed and paraffin
      embedded sections of the human endometrium and placental villi. In 53 endometrial
      biopsy specimens, labeled nuclei were identified in 16 samples showing a
      desquamating change, associated with menstruation, functional bleeding or
      adenocarcinoma. Cells in the normal proliferative and secretory phases were
      unlabeled. The labeled nuclei in the gland and stroma corresponded well to the so
      called apoptotic bodies. Placental tissues at various stages of gestation were
      obtained by spontaneous abortion, intrauterine fetal death or normal delivery.
      Syncytiotrophoblastic cells in an early gestational stage (7-12 weeks) and in the
      term placenta were focally labeled, and the labeled cells possessed pyknotic
      nuclei and densely eosinophilic cytoplasm. In the early gestational chorionic
      villi with marked hydropic degeneration or in hydatidiform mole, the stromal
      cells were frequently labeled. Villous cells in coagulation necrosis (infarction)
      also revealed strong signals. The apoptotic bodies were not recognizable
      histologically in these labeled villi. The placenta at the 20th to 33rd week of
      gestation lacked labeling. From a technical point of view, it should be noted
      that cells in the foci showing ischemia or coagulation necrosis were labeled
      positively.

PMID- 7576871
TI  - Apoptosis and heterophagy of medial edge epithelial cells of the secondary
      palatine shelves during fusion.
AB  - Recent in vivo and in vitro studies have suggested that medial edge epithelial
      (MEE) cells covering the lateral palatine shelves do not undergo cell death, but
      migrate into the oral and nasal epithelium or transform into mesenchymal cells.
      We, therefore, reexamined the fate of MEE cells during palatal fusion in rat
      embryos by in situ 3' nick end labeling of dUTP (TUNEL), electron microscopy, and
      immunohisto/cytochemistry. TUNEL staining revealed positive nuclei in the medial
      edge epithelium immediately prior to contact, in epithelial triangles formed
      between the epithelial seam and nasal or oral epithelium, in epithelial pearls,
      and in mesenchymal tissue near the epithelium. However, these TUNEL-positive
      cells were rarely present in the epithelial seam. Electron microscopy revealed
      MEE cells showing nuclear chromatin condensation and cell shrinkage, and
      apoptotic bodies in the fusing epithelium; these often contained apoptotic body
      like structures as heterophagosomes. By double staining using a laser scanning
      microscope, TUNEL-positive nuclei were co-localized with lysosomal cysteine
      proteinases, cathepsin B or L in MEE and mesenchymal cells adjacent to the
      epithelium. These results suggest that MEE cells undergo apoptosis during the
      palatal formation, even though they migrate into epithelial triangles or
      transform into mesenchymal cells. Moreover, apoptotic bodies and cellular debris
      were phagocytosed by adjacent MEE cells or mesenchymal cells and digested by
      lysosomal enzymes.

PMID- 7576873
TI  - Apoptosis of mouse pancreatic acinar cells after duct ligation.
AB  - It has been established that pancreatic exocrine acinar cells disappear after
      pancreatic duct obstruction. This study aimed to examine the relationship between
      the disappearance of the acinar cells and apoptosis after pancreatic duct
      ligation of the splenic lobe in dd-mice, six weeks of age. In some mice, the
      ligature was removed after two or three days. In addition to general light and
      electron microscopic examinations on the pancreatic tissues, paraffin sections
      stained with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end labeling (TUNEL) method were observed to detect nuclear DNA fragmentation.
      Pancreatic acinar cells underwent apoptosis initiated with nuclear DNA damages
      three days after duct ligation and were completely deleted by seven days. Due to
      the elevation of the intraluminal pressure, the acinar cells showed interrupted
      secretion of their zymogen granules and disorganization of their rough
      endoplasmic reticulum, causing the cessation of granule formation before
      apoptosis started. These cytoplasmic changes prior to apoptosis are reversible,
      as observed after removal of the ligation. Apoptosis of the acinar cells was
      indentified by TUNEL-labeling of the nuclei, the condensation and margination of
      nuclear chromatin, and round fragmentation of cell bodies, all irreversible
      changes. Apoptosis of acinar cells seemed to stimulate the proliferation of duct
      cells, which comprised the main cell components in the exocrine pancreas after
      the disappearance of acinar cells.

PMID- 7576872
TI  - The fate of effete epithelial cells at the villus tips of the human small
      intestine.
AB  - Until recently, little has been known about the morphological features of dying
      enterocytes at the villus tips of the human small intestine. The present study
      aimed to show the exfoliating processes of effete enterocytes at the villus tips.
      Cellular elements of the duodenal lumen and jejunal tissue in humans were fixed
      and processed for DNA nick end labeling (TUNEL), and transmission and scanning
      electron microscopy (TEM and SEM). Most cellular elements in the duodenal lumen
      were enterocytes having TUNEL-positive nuclei. By SEM, protruding enterocytes
      were discerned at the villus tips. Using the SEM samples embedded in epoxy resin,
      protruding enterocytes were observed at the villus tips by TEM; they were shrunk
      by forming numerous clear and autophagic vacuoles, took dome-like profiles, and
      possessed nuclei with chromatin condensation. The intercellular spaces beneath
      these protruding or effete enterocytes were often occupied by large lymphocytes.
      By TUNEL reaction, positive stainings appeared in the epithelium not only at the
      tip of the villi but also around the site. The results suggest that effete
      enterocytes at the villus tips of human small intertine are first shrunk by
      forming clear and autophagic vacuoles, and showed that their nuclei exhibit
      chromatin condensation immediately before being exfoliated into the lumen.

PMID- 7576874
TI  - Multinucleated giant cells undergoing apoptosis in experimental autoimmune
      myocarditis.
AB  - This study used an experimentally induced myocarditis model in rats to
      demonstrate the formation and fate of multinucleated giant cells which are known
      to occur in different kinds of inflammatory lesions. Multinucleated giant cells
      were frequently recognized in the inflammatory foci, being intermingled with
      numerous ED1-positive inflammatory macrophages rich in phagosomes. The giant
      cells reacted with the ED1 antibody but not with ED2, and ultrastructurally
      resembled the inflammatory macrophages. Multinucleated giant cells possessing
      less than 5 nuclei in an ultrathin section were rich in phagosomes, whereas those
      with more nuclei contained numerous lipid droplets and only few phagosomes in
      their cytoplasm. Light microscopic observation of hematoxylin-eosin stained
      sections revealed that some multinucleated giant cells displayed variously sized
      dark bodies which likely corresponded to condensed and fragmented nuclear
      chromatin. Such multinucleated giant cells were positively stained with the TUNEL
      method. Under the electron microscope, all nuclei in one multinucleated giant
      cell showed an eccentric mass of homogeneously condensed chromatin. These
      observations suggest that multinucleated giant cells are formed by aggregation
      and also likely by fusion of inflammatory macrophages; gradually loosing the
      phagocytotic activity characteristic of the latter cells, they then die by
      apoptosis.

PMID- 7576877
TI  - The process of apoptosis in follicular epithelial cells in the rabbit ovary, with
      special reference to involvement by macrophages.
AB  - Using rabbit ovaries, this study investigated the fate of follicular epithelial
      cells undergoing apoptosis in follicle atresia, especially in atretic Graafian
      follicles. This is the first report to apply the TUNEL method and histochemistry
      for acid phosphatase in order to demonstrate macrophages immigrating into the
      follicles to eliminate the apoptotically dead epithelial cells. At initial stages
      of atresia, a few epithelial cells solitarily revealed the condensation of
      nuclear chromatin characteristic of apoptosis, simultaneously reacting positive
      to the TUNEL method. At advanced stages, chromatin condensation and separation as
      well as cytoplasmic fragmentation spread to the entire follicular epithelium. In
      such an advanced atretic follicle, large round cells appeared in the follicular
      lumen; these could be identified as macrophages by their morphologies and
      positive reactions for acid phosphatase. These macrophages were adhering to and
      internalizing apoptotic epithelial cells and their fragments until the lumen
      became completely free of dead cells and fragments.

PMID- 7576876
TI  - Most thymocytes die in the absence of DNA fragmentation.
AB  - Most thymocytes are known to be depleted from the thymus during T cell
      development, with the process of thymocyte death considered to be apoptosis. In
      this study we examined the mechanism of thymocyte death in the thymus of 6-week
      old mice by using terminal deoxynucleotidyl transferase to detect DNA
      fragmentation or double strand breaks (TUNEL method). The TUNEL positive
      thymocytes were scattered throughout the cortex. Double staining of the section
      with the TUNEL method and acid phosphatase (ACP) activity showed that all the
      TUNEL positive cells were phagocytosed by ACP positive macrophages. An ultra
      structural study revealed the presence of a substantial number of extremely
      small, unphagocytosed thymocytes throughout the cortex. These small
      unphagocytosed thymocytes were apparently dead cells, as based on several
      morphological features: 1) The majority were much smaller than red blood cells;
      2) the nuclei were also considerably small; and 3) the extent of chromatin
      condensation was enormous. Importantly, these unphagocytosed dead thymocytes were
      TUNEL negative. These results indicate that: 1) DNA fragmentation, which is
      detected by the TUNEL method, is not involved in the cell death process of small
      unphagocytosed dead thymocytes shown in the present study; and that 2) typical
      apoptosis, which is characterized by DNA fragmentation, is not the dominant type
      of cell death in the normal murine thymus. Processes of cell death other than
      typical apoptosis taking place in most thymocytes require further investigation.

PMID- 7576875
TI  - Expression of apogens and engulfens during programmed cell death in the nervous
      system of the chick embryo.
AB  - Two categories of cell death related to antigens, apogens and engulfens, have
      been reported to be expressed by apoptotic cells and the cells involved in their
      engulfment in the immune system, and in mesenchymal tissue in the limb of the
      chick embryo (ROTTELLO et al., 1994). To determine whether these antigens are
      also expressed during the process of neuronal death, the distribution of
      immunoreactivity to both anti-apogen and anti-engulfen antibodies was examined in
      the spinal cord and the dorsal root ganglia of the chick embryo. Anti-apogen
      antibodies labeled a sub-population of the profiles of dying cells in regions
      where cell death was occurring. The extent of labeling by anti-apogens varied
      from 3% to 70% of the total number of dying profiles depending on the specific
      antibody used and the neuronal region examined. Immunoreactive labeling by the
      anti-engulfen antibodies mainly involved large cells that contained debris of
      dead cells. These results indicate that at least some dying neuronal cells
      express common antigens that are shared by dying mesenchymal cells during
      programmed cell death, and that phagocytotic cells of the immune system are
      involved in the engulfment of neuronal cells that have undergone programmed cell
      death.

PMID- 7576878
TI  - Juvenile myoclonic epilepsy.
AB  - Juvenile myoclonic epilepsy is a relatively common, though under diagnosed, form
      of epilepsy that commences in adolescence. The distinguishing symptoms, diagnosis
      and medical management are discussed.

PMID- 7576879
TI  - Accidental death or sudden infant death syndrome?
AB  - OBJECTIVE: To describe the reasons why it is difficult to decide whether to
      attribute some infant deaths to accidents or to SIDS. METHODOLOGY: To extract
      from infant deaths data in South Australia those where the cause of death is
      debatable. RESULTS: The risks associated with rocking cradles, bed sharing,
      bedclothes, couch sleeping, unsafe cots or beds and the prone position are
      presented. CONCLUSIONS: Uniform worldwide death scene investigations for all
      infant deaths should help identify unsafe sleeping conditions for infants.

PMID- 7576880
TI  - Towards a better understanding of childhood asthma.
AB  - OBJECTIVE: To explore the ways asthma may be defined in childhood and consider
      the current evidence to support these possible definitions. METHODOLOGY: The
      relationship of symptoms, atopy, bronchial hyperresponsiveness (BHR) and airway
      inflammation in defining childhood asthma is reviewed. RESULTS: While none of the
      four proposed methods of defining asthma can stand alone as the 'gold standard',
      in childhood asthma, all four, namely clinical symptoms, atopy, BHR and airway
      inflammation, are intimately related. The degree of atopy and BHR, and the
      presence of airway inflammation, should be viewed as significant risk factors for
      persistent wheezing in childhood. CONCLUSION: At present the clinical diagnosis
      of asthma in childhood remains largely based on symptoms but it is likely that,
      with further research, the group of children who are now labelled as having
      asthma will be subdivided into different subgroups with implications for both
      treatment and outcome.

PMID- 7576881
TI  - Tongue-tie.
AB  - OBJECTIVE: To review the presenting features of tongue-tie in childhood and
      indications for frenulotomy, drawing conclusions from a retrospective study of
      patients encountered in paediatric surgical practice and from the literature.
      METHODOLOGY: A disease index was kept enabling histories to be selected for
      analysis. All patients were seen by the author and all operations performed by
      the author or a registrar under supervision in a standard manner. Patients were
      reviewed 2 weeks after operation. RESULTS: During 18 years of practice, 287
      patients with simple tongue-tie were encountered (two others with true
      ankyloglossia were not included in this study) and 158 frenulotomies were
      performed. The presenting symptoms were related to sucking or swallowing (13%),
      speech (32%), mechanical problems related to restricted tongue movements (14%)
      and to other problems (3%). In 38% the asymptomatic tongue-tie was noted
      incidentally. CONCLUSION: It is concluded that there is no place for division of
      tongue-tie without anaesthesia in the newborn. Speech difficulties related to
      tongue-tie are over-rated and mechanical problems are underestimated. The
      indications for frenulotomy include articulation difficulties confirmed by a
      speech pathologist, mechanical limitations such as inability to lick the lips, to
      perform internal oral toilet or play a wind instrument. There may be rare
      instances in infancy where problems with feeding and suction can be helped by
      frenulotomy but evidence for this is anecdotal. Operation requires general
      anaesthesia except in older, co-operative teenagers in whom local anaesthetic is
      appropriate.

PMID- 7576883
TI  - The origins of cerebral palsy. Australian and New Zealand Perinatal Societies.

PMID- 7576882
TI  - Neurometrics, dynamic brain imaging and attention deficit hyperactivity disorder.
AB  - OBJECTIVE: The literature on the development of frequency analysis of the
      electroencephalogram (neurometrics) and functional dynamic brain imaging
      techniques is reviewed. Clinical applications in the diagnosis and treatment of
      learning disorders of childhood are discussed. CONCLUSIONS: While questions
      remain about the sensitivity and specificity of the neurometric method in
      diagnosing attention deficit hyperactivity disorder (ADHD), if the technique
      proved predictive of medication response, its importance would be established.
      However, evoked-potential studies, cerebral blood flow and cerebral glucose
      metabolic studies promise a better understanding of underlying psychological
      processes in ADHD.

PMID- 7576885
TI  - High frequency oscillation in newborn infants with respiratory failure.
AB  - OBJECTIVE: To report ventilation strategies, survival and complications in 39
      outborn infants treated with high frequency oscillatory ventilation (HFOV).
      METHODOLOGY: Data were collected prospectively between 1 May 1992 and 31 December
      1993 on all infants treated with HFOV who had severe respiratory failure despite
      optimal conventional ventilation. RESULTS: Twenty-eight out of 39 (72%) survived.
      Of the 15 infants with birthweights < 1500 g, eight survived. Best survival rates
      were for infants with pulmonary interstitial emphysema with air leak (4/5) and
      for infants of birthweight > 1500 g with hyaline membrane disease (8/8), and
      meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and
      required extracorporeal membrane oxygenation. Complications were: (i) development
      of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3);
      (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight
      infants weighing < 1500 g who received HFOV in the first week of life developed
      periventricular haemorrhage. CONCLUSION: The initial results of HFOV for severe
      failure were encouraging although a learning curve was encountered with its
      introduction.

PMID- 7576886
TI  - High frequency oscillatory ventilation: initial experience in 22 patients.
AB  - OBJECTIVES: To report the outcome of a consecutive cohort of neonates treated
      with high frequency oscillatory ventilation (HFOV). METHODOLOGY: Prospective
      cohort study of 22 neonates failing conventional mechanical ventilation (CMV)
      between October 1992 and August 1993. Outcomes evaluated were in-hospital
      survival rate, comorbidities including patent ductus arteriosus (PDA),
      cerebroventricular haemorrhages (CVH), necrotizing enterocolitis (NEC),
      bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP), and acute
      changes in respiratory status. RESULTS: Eighteen of 22 (81.8%) survived. Of the
      four children who died, one did not respond to HFOV and died within 24 h of
      treatment. Two died of respiratory failure complicated by pulmonary haemorrhage.
      The remaining infant responded to HFOV but later developed severe NEC while on
      minimal CMV and died at 2 weeks of age. Three subjects were > or = 34 weeks'
      gestation; each responded well to HFOV with no substantial comorbidity. Of the
      remaining 19 infants < 34 weeks' gestation, six (31.6%) had a PDA, and seven
      (36.8%) had a CVH. One infant developed cystic periventricular leucomalacia.
      Three infants (15.8%) had NEC. Respiratory failure in the 15 survivors with
      gestational ages < 34 weeks improved dramatically with HFOV. Ten (66.7%)
      survivors < 34 weeks developed BPD and 10 (66.7%) ROP. CONCLUSION: High frequency
      oscillatory ventilation was associated with a survival rate of 81.8%, but with
      significant comorbidity.

PMID- 7576887
TI  - Technology seduction: lost opportunities in child health?
AB  - This report examines the extent to which illness-based individual care and
      expensive, often unevaluated, technologies in paediatrics have seduced
      practitioners away from more cost-effective, population-based child health
      activities and examples of new and unevaluated technologies in perinatology and
      paediatrics are given. The way in which these technologies are introduced and
      taken up, by 'creeping incrementalism', is described and a plea is made to
      implement only those aspects of paediatric care that have been demonstrated to be
      effective. This would result in only appropriate technologies being used, avoid
      harm being done to children and ensure that money is available for other
      effective population-based activities that improve child health.

PMID- 7576884
TI  - Inter-rater reliability in the medical diagnosis of child sexual abuse.
AB  - OBJECTIVE: To examine inter- and intra-rater reliability in the assessment of
      genital findings in cases of suspected child sexual abuse. METHODOLOGY:
      Colposcopic photographs of the external genitalia of 70 female children were
      independently assessed by child sexual abuse teams in Auckland and Sydney. For
      the Auckland centre, intra-rater reliability was assessed by making a second
      independent assessment 6 months following the first. Reliability was quantified
      using per cent of agreement and Cohen's Kappa statistic. RESULTS: There were high
      levels of inter- and intra-rater agreement. When photographs were classified as
      normal/non specific or strongly indicative of child sexual abuse, there was 93%
      agreement between the Auckland and Sydney teams with a kappa score of 0.70. For
      the two separate ratings made by the Auckland team there was 94% agreement with a
      kappa score of 0.75. CONCLUSIONS: The high levels of inter- and intra-rater
      agreement obtained in this study were reassuring. The results obtained compare
      favourably with the results of reliability studies in other areas of medical
      practice.

PMID- 7576889
TI  - Risk factors for sensorineural hearing loss in extremely premature infants.
AB  - OBJECTIVE: To identify potentially preventable risk factors for sensorineural
      hearing loss (SNHL) in extremely premature infants. METHODOLOGY: A case control
      study of survivors with gestational age (GA) < 28 weeks or birthweight (BW) <
      1000 g using data collected prospectively in our Neonatal Intensive Care Unit
      database. Each subject with bilateral SNHL > 40 dB was matched according to GA,
      BW and sex with two controls who had neither sensorineural nor conductive hearing
      loss. RESULTS: Infants with SNHL had increased mean (+/- s.d.) days ventilated
      (53 +/- 21 vs 37 +/- 23 days, P = 0.006) and in oxygen (107 +/- 44 vs 69 +/- 28
      days, P = 0.02) compared with controls. The risk for SNHL was increased for
      infants who spent > 90 days in oxygen (OR 4.0 [95% CI 1.1-15.6]), had maximum
      FiO2 > 0.90 (5.6 [1.2-26.9]), minimum plasma Na < 125 mmol/L (5.6 [1.1-27.8] or
      maximum pH > 7.60 (5.6 [1.1-89.0]). Neither maximum serum bilirubin nor exposure
      to ototoxic drugs was associated with SNHL. CONCLUSIONS: Avoidance of severe
      hyponatraemia and extreme alkalosis, as well as use of surfactant to minimize the
      severity of hyaline membrane disease, may result in a decreased incidence of SNHL
      in extremely premature infants.

PMID- 7576888
TI  - Neonatal herpes simplex infection: keys to early diagnosis.
AB  - OBJECTIVE: To highlight the clinical features of neonatal herpes simplex (HSV)
      infection that might facilitate earlier diagnosis. METHODOLOGY: Fifteen year
      retrospective review of proven neonatal HSV cases from a regional neonatal
      referral unit. RESULTS: Fifteen cases reviewed: 10 with central nervous system
      (CNS) disease, three with skin, eyes or mouth (SEM) disease and two with
      disseminated disease (DIS). A median 4 day delay occurred between symptom onset
      and hospital admission. All cases presented after maternity hospital discharge,
      most commonly with feeding problems and lethargy. Six patients presented with
      skin lesions; parental genital herpes was reported in three (20%) cases. Seven
      infants died, four without acyclovir treatment and three of 11 treated cases.
      Three of five CNS disease survivors and all infants with SEM disease were normal
      at follow up. CONCLUSIONS: Acyclovir improves outcome in neonatal HSV infection.
      To improve outcome further earlier recognition of the non-specific presenting
      features of the disease is required.

PMID- 7576890
TI  - Invasive pneumococcal infection in children, 1981-92: a hospital-based study.
AB  - OBJECTIVE: To document the pattern and sequelae of invasive pneumococcal
      infection in hospitalized children. METHODOLOGY: Retrospective review of
      Streptococcus pneumoniae (Sp) isolates from normally sterile sites from 1981 to
      1992 at three paediatric centres in Sydney for demographic data, spectrum of
      disease, predisposing conditions, mortality, and sequelae from meningitis.
      RESULTS: Four hundred and thirty-one episodes in 417 patients were identified.
      Foci of infection were: meningitis, 34%; pneumonia, 29%; bacteraemia without
      apparent focus, 30%; and other foci, 7%. Sixty-one per cent of all cases and 64%
      of cases with meningitis were less than 2 years old. Predisposing conditions were
      present in 37%, were significantly more common in patients over age 2 years and
      were more common with foci other than meningitis. Overall mortality was 6.6%
      whereas the mortality for those with meningitis was 8%. Neurological sequelae
      were identified in 34% of previously normal children, and severe hearing loss
      occurred in 11.5%. CONCLUSIONS: The high morbidity and mortality from invasive
      pneumococcal infection in children justifies further evaluation of preventive
      strategies.

PMID- 7576891
TI  - Follow-up validation study of the Victorian Congenital Malformations Register.
AB  - OBJECTIVE: To determine whether there has been an improvement in ascertainment of
      malformations in the Victorian Congenital Malformations Register (VCMR).
      METHODOLOGY: The medical records of 500 children under 4 years of age admitted
      consecutively to two paediatric teaching hospitals in Victoria in 1992 were
      viewed to determine whether these cases had been notified to the Register.
      RESULTS: Over three-quarters of the defects recorded had been notified to VCMR.
      There was 100% ascertainment of chromosomal anomalies and a high proportion of
      major structural malformations were notified. CONCLUSION: This study repeats the
      validation study completed in 1986 and shows marked improvement in ascertainment
      of malformations in the VCMR by 1992.

PMID- 7576892
TI  - The Fremantle Lead Study.
AB  - OBJECTIVE: To ascertain blood lead levels in a sample of preschool children from
      Framantle, Western Australia, and to correlate these with possible risk factors.
      METHODOLOGY: The study was a cross-sectional prevalence survey of 120 children
      from day-care centres and 44 hospital inpatients. Blood lead and ferritin levels
      were determined and a risk factor questionnaire was completed by parents.
      RESULTS: Of the 164 children 25.6% had lead levels above the NH&MRC goal (< 10
      micrograms/dL). Nine of 133 (6.7%) had ferritin levels below 10 micrograms/L
      suggesting iron deficiency. Excessive blood lead concentrations as defined by the
      NH & MRC (> 9 micrograms/dL) related to: child's presence during house renovation
      (OR 3.35, P = 0.007, 95% CI 1.39-8.81); Aboriginality (OR 6.4, P = 0.008, 95% CI
      1.6-24.9), and, in the 9-24 month age group, inversely to distance between home
      and a road carrying > 7000 vehicles/day (r -0.56, P = 0.009, n = 24).
      CONCLUSIONS: A group of Fremantle children with unacceptably high blood lead
      levels has been identified. Renovation of older housing and Aboriginality are
      important risk factors.

PMID- 7576893
TI  - Herpes simplex virus infections in the neonate.
AB  - OBJECTIVE: To review the experience of the Camperdown Children's Hospital with
      neonatal herpes simplex viral (HSV) infections between 1960 and 1992. DESIGN: A
      retrospective record review of all cases of HSV infection. RESULTS: Fifteen
      proven HSV infections were found. Only three cases had a definite history of HSV
      infection during pregnancy. Six were delivered at 36 weeks gestation or earlier.
      Seven weighed 2500 g or less. Forty-three per cent developed physical signs
      within 7 days of birth. Three cases were confined to skin, eyes and mouth, five
      were generalized, six had encephalitis with or without skin lesions, and one had
      pneumonitis. The mortality rate comprising the five with generalized infection
      was 47%, one with encephalitis and the one with pneumonitis. Four of the eight
      survivors have persisting neurological impairment. Those with disseminated
      infection and encephalitis did poorly regardless of antiviral treatment.
      CONCLUSION: A high index of suspicion of HSV infection is important so that
      antiviral treatment can be commenced early, particularly for those infections
      localized to skin, eye and mouth where there may be a good prognosis.

PMID- 7576894
TI  - Anti-neutrophil cytoplasmic antibodies in Japanese children with ulcerative
      colitis.
AB  - OBJECTIVE: To investigate the diagnostic value of anti-neutrophil cytoplasmic
      antibodies (ANCA) in the diagnosis of ulcerative colitis (UC) in Japanese
      children. METHODOLOGY: Serum samples from 23 children with UC (17 Japanese, 6 non
      Japanese), 27 children with Crohn's disease (CD) (10 Japanese, 17 non-Japanese),
      10 children with other diarrhoeal diseases, and 33 normal, healthy adult
      volunteers were assayed for ANCA using an indirect immunofluorescence technique.
      RESULTS: ANCA were detected in 6/17 (35%) UC patients and 0/10 (0%) CD patients
      in Japanese children, and in 3/6 (50%) UC patients and 3/17 (18%) CD patients in
      non-Japanese children. The difference in prevalence between Japanese and non
      Japanese children with UC was not statistically significant (P > 0.05). ANCA were
      not found in other diarrhoeal patients and volunteers. CONCLUSIONS: Although ANCA
      have been reported to be useful in the diagnosis of UC in adults, they may be of
      limited use in Japanese children. This might reflect the heterogeneity of UC.

PMID- 7576895
TI  - Selenium status of New Zealand infants fed either a selenium supplemented or a
      standard formula.
AB  - OBJECTIVE: New Zealand soils are deficient in the essential micronutrient,
      selenium. New Zealand infants have low selenium levels at birth and experience a
      further decline if fed cows milk based formula. This study examined the selenium
      status of infants fed with a new commercially available selenium supplemented
      formula. METHODOLOGY: Forty-four newborn infants, whose mothers wished to formula
      feed, were randomized in an open controlled trial to be fed a commercially
      available selenium supplemented cows milk formula (containing 17 micrograms Se/L)
      or an unsupplemented formula (containing 4.6 micrograms Se/L). Cord, 1 and 3
      month blood samples were obtained for selenium status (plasma and red cell
      selenium and glutathione peroxidase) and thyroid function. RESULTS: Mean plasma
      selenium and glutathione peroxidase values were significantly higher in
      supplemented than unsupplemented infants at 1 month (unpaired t-tests; P < 0.0001
      and P = 0.001 respectively) and 3 months (P < 0.0001 and P = 0.0005). Analysis
      within treatment groups between time points (paired t-tests) showed that selenium
      supplementation prevented the fall in plasma selenium from birth to 1 month seen
      in unsupplemented infants and was associated with a rise in levels between 1 and
      3 months (P = 0.002). CONCLUSIONS: Supplementing cows milk formula with selenium
      to replicate the levels found in breast milk is nutritionally sound. Feeding from
      a few days of age with a formula containing 17 micrograms Se/L in infants with
      low selenium status at birth is sufficient to cause a rise to 80% of adult levels
      at 3 months of age.

PMID- 7576896
TI  - Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated aboriginal
      and Torres Strait Island children.
AB  - OBJECTIVE: To determine the immunity to hepatitis B, poliomyelitis and measles in
      fully vaccinated Aboriginal and Torres Strait Island children in north
      Queensland. METHODOLOGY: A cross-sectional survey of immunity in a sample of
      children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with
      a median age of 24.5 months, from 10 communities in North Queensland participated
      in this study. The main outcome measures were the prevalence of adequate antibody
      levels against hepatitis B, poliomyelitis and measles. RESULTS: Only 54% (95% CI
      44-63%) of the children had adequate immunity (> or = 10 m iu/mL) to hepatitis B,
      and one child had been infected despite vaccination. Although all the children
      (95% CI 96-100%) had adequate immunity (i.e. neutralizing antibodies at a
      dilution of > or = 1:8) to poliovirus 2, only 93% (95% CI 86-96%) and 60% (95% CI
      50-69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all
      (96%; 95% CI 90-98%) of the children had adequate immunity (i.e. detectable IgG
      antibody) to measles. CONCLUSIONS: Although a relatively low proportion of the
      children had adequate antibody levels against hepatitis B the clinical
      significance of this observation is uncertain. Further studies are needed to
      determine whether fully vaccinated Torres Strait Island children have been
      adequately protected and whether they require a booster dose of hepatitis B
      vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres
      Strait Island children are inadequately protected against poliomyelitis, and
      therefore any such child with acute flaccid paralysis should be investigated
      fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children
      are well protected against measles, as are other Australian children.

PMID- 7576897
TI  - Effect of a postural support nappy on 'flattened posture' of the lower
      extremeties in very preterm infants.
AB  - OBJECTIVE: To determine whether the use of a postural support nappy (PSN) would
      reduce the features of 'flattened posture' in the lower extremities of infants <
      31 weeks gestation who are nursed prone. METHODOLOGY: Randomized, observer blind,
      controlled trial conducted at King Edward Memorial Hospital for Women, Perth,
      Western Australia. Infants were randomly assigned and stratified by gestational
      age to be nursed in a conventional nappy (n = 29) or a PSN (n = 31) when in the
      prone position. The features of 'flattened posture' were measured as angles and
      assessed by blinded observers prior to commencement of the intervention, 4 weeks
      post intervention, then bi-weekly until discharge. RESULTS: A significant
      reduction in the features of 'flattened posture' occurred in the PSN group after
      4-6 weeks of intervention and stabilized by 8 weeks until discharge. No changes
      were detected in the control group. No significant difference was observed
      between infants < 29 weeks gestation compared to infants of 29-30 weeks gestation
      in either treatment group. CONCLUSIONS: Use of the PSN in infants < 31 weeks
      gestation who are nursed in the prone position significantly reduces the features
      of 'flattened posture' in the lower extremities. This is of benefit in the short
      term, and follow up of these infants into childhood will demonstrate whether the
      long-term effects of 'flattened posture' can be prevented.

PMID- 7576898
TI  - Kawasaki disease associated with streptococcal infection within a family.
AB  - OBJECTIVE: To describe the illness occurring in four members of a family, which
      had clinical and laboratory features of Kawasaki disease and streptococcal
      infection. METHODOLOGY: A retrospective report of three siblings and an adult
      male living in one household. The children had serology, blood counts, cultures
      and echocardiography performed and were treated with antibiotics and
      gammaglobulin infusions. RESULTS: The patients developed clinical, and exhibited
      laboratory, features suggesting streptococcal infection and 4/5 criteria
      suggesting the diagnosis of Kawasaki disease. All made a good clinical recovery
      but the youngest developed a coronary artery aneurysm. CONCLUSIONS: It may be
      difficult to distinguish streptococcal infection and Kawasaki disease. It is
      possible that some cases of Kawasaki disease are precipitated by streptococcal
      infection.

PMID- 7576901
TI  - Survey on developmental-behavioural training experiences of Australian paediatric
      advanced trainees.

PMID- 7576899
TI  - Agnathia (severe micrognathia), aglossia and choanal atresia in an infant.
AB  - A neonate is reported here, who was born with severe mandibular hypoplasia,
      complete absence of the tongue, unilateral choanal atresia, contralateral choanal
      stenosis and developed severe airway obstruction at birth. Arrested development
      of the ventral first branchial arch most likely underlies the clinical deficits.
      Most reported cases of agnathia have been lethal but the infant reported here has
      survived into infancy with a tracheostomy and feeding gastrostomy. Her clinical
      features, assessment and management are discussed.

PMID- 7576900
TI  - Congenital heart disease: a 10 year cohort.

PMID- 7576902
TI  - Hib immunization.

PMID- 7576903
TI  - Plant sources of acid stable lipases.

PMID- 7576906
TI  - Therapy methods for cerebral palsy.

PMID- 7576904
TI  - Therapy methods for cerebral palsy.

PMID- 7576905
TI  - Therapy methods for cerebral palsy.

PMID- 7576907
TI  - Therapy methods for cerebral palsy.

PMID- 7576908
TI  - Expression and characterization of CD4-IgG2, a novel heterotetramer that
      neutralizes primary HIV type 1 isolates.
AB  - CD4-IgG2 is a novel fusion protein comprising human IgG2 in which the Fv portions
      of both heavy and light chains have been replaced by the V1 and V2 domains of
      human CD4. This tetrameric protein is being developed as an immunoprophylactic
      agent to reduce the probability of infection following HIV-1 exposure, in
      settings such as occupational or perinatal exposure to the virus. CD4-IgG2 has
      been expressed in Chinese hamster ovary cells and is secreted as a fully
      assembled heterotetramer. The protein binds with nanomolar affinity to purified
      gp120 from both a laboratory-adapted strain and a primary isolate of HIV-1.
      Pharmacokinetic studies in rabbits demonstrated that CD4-IgG2 has a plasma
      terminal half-life greater than 1 day, compared with 15 min for soluble CD4
      (sCD4). CD4-IgG2 does not bind to Fc receptors on the surface of U937
      monocyte/macrophage cells. Compared to molecules that incorporate the Fc portion
      of IgG1, CD4-IgG2 has less potential to mediate functions such as antibody
      dependent enhancement of infection or transplacental transmission of HIV-1. When
      tested in a virus-free HIV-1 envelope glycoprotein-mediated cell fusion assay,
      the tetrameric CD4-IgG2 molecule inhibited syncytium formation more effectively
      than monomeric sCD4 or a dimeric CD4-gamma 2 fusion protein. This suggests the
      protein will block cell-to-cell transmission of HIV-1. Moreover, CD4-IgG2
      effectively neutralized a panel of laboratory-adapted strains and primary
      isolates of HIV-1, including strains with different tropisms and isolated from
      different stages of the disease, at concentrations that should be readily
      achieved in vivo.

PMID- 7576909
TI  - Inhibition of HIV type 1 infection of mononuclear phagocytes by anti-CD44
      antibodies.
AB  - Cellular CD4 is the primary membrane molecule that binds HIV-1 through
      interaction with viral gp120. Membrane glycolipids and cell adhesion molecules
      have also been noted to be involved in the interaction of HIV-1 with cells and in
      syncytium formation in infected cells. The purpose of this study was to determine
      the role of the cell adhesion molecule CD44 in HIV-1 infection of cells. Both
      normal blood monocytes and lymphocytes expressed CD44 as determined by flow
      cytometry using the anti-CD44 antibody A3D8. Anti-CD44 monoclonal antibodies
      A3D8, A1G3, and 5F12 [ascites, purified IgG, and F(ab')2] inhibited infection of
      monocytes and peritoneal macrophages with HIV-1-BaL and HIV-1-ADA, but had no
      effect on HIV-1-IIIB infection of mitogen-stimulated lymphocytes, or cells of a T
      lymphocyte line. CD44 monoclonal antibodies were not toxic for monocytes, and the
      observed inhibitory effect of CD44 monoclonal antibodies was not dependent on
      complement. These results suggest that CD44 may be a determinant of HIV-1
      infection of mononuclear phagocytes in vitro.

PMID- 7576910
TI  - HIV type 1 grown on interferon gamma-treated U937 cells shows selective increase
      in virion-associated intercellular adhesion molecule 1 and HLA-DR and enhanced
      infectivity for CD4-negative cells.
AB  - Cellular adhesion molecules, such as ICAM-1, -2, and -3; LFA-1; and HLA class I
      and II are incorporated into HIV-1 virions during budding from infected cells.
      These virion-associated molecules can be involved in the adsorption to
      susceptible cells displaying the corresponding counterligands. A number of
      cytokines have been shown to upregulate the cellular expression of adhesion
      molecules, such as ICAM-1 and HLA-DR. In this study we investigated the effects
      of IFN-gamma on the incorporation of ICAM-1, LFA-1, and HLA-DR into mature HIV-1
      progeny from chronically infected cells. The ability of such virus progeny to
      infect either CD4-positive or -negative cells was also investigated. The results
      indicate that IFN-gamma stimulates the expression of ICAM-1 and of HLA-DR on HIV
      1-infected cells, whereas LFA-1 expression is unaffected. The same modifications
      were also observed on virus progeny, because specific MAbs to ICAM-1 and HLA-DR
      captured infectious HIV-1 from IFN-treated cells with higher efficiency as
      compared to virus from control cells, whereas virus binding to anti LFA-1 MAb was
      unchanged. Moreover, the HIV-1 progeny released from IFN-treated cells showed an
      increased ability to bind to and to infect CD4-negative cells, whereas the
      infectivity was basically unchanged for CD4-positive cells. Our results suggest
      that cytokines, as well as other soluble factors, may expand the host cell range
      of HIV-1, possibly through modifications of the cell-derived surface molecules on
      the virions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576911
TI  - Insulin-like growth factor 1 and insulin inhibit HIV type 1 replication in
      cultured cells.
AB  - Insulin-like growth factor 1 and insulin, considered primarily as metabolic and
      growth modulatory hormones, were found to inhibit the replication of HIV-1 in
      cultured cord blood mononuclear cells and chronically HIV-infected U937 cells.
      The effect of IGF-1 was seen at physiological concentrations or lower (1.7 x 10(
      10) M) while that of insulin was observed at supraphysiological concentrations (8
      x 10(-7) M). The EC50 for IGF-1 was found to be in the physiological range (2.5
      4.5 x 10(-9) M) while that for insulin was considerably higher (1.1-3.3 x 10(-6)
      M). Insulin-like growth factor 1 and insulin at the concentrations employed
      exhibited no toxicity on the cells used in these studies. Furthermore, neither
      IGF-1 nor insulin exhibited any inhibitory activity on purified reverse
      transcriptase in vitro. Epidermal growth factor from 1.6 x 10(-10) to 1.6 x 10(
      8) M demonstrated no inhibition of HIV-1 replication, while IGF-1 inhibited p24
      antigen production 49 and 42% at 1.3 x 10(-9) and 1.3 x 10(-8) M IGF-1,
      respectively. These results suggest that IGF-1 under certain conditions has
      significant inhibitory effects on HIV-1 replication at physiological
      concentrations. This may prove to be of therapeutic value in patients infected
      with HIV-1.

PMID- 7576912
TI  - Characterization of V3 loop-binding protein(s) of Molt-4 and U937 cells.
AB  - The V3 loop in gp120 of human immunodeficiency virus type 1 (HIV-1) is known as a
      principal neutralizing and cell-tropic determinant. Biotinylated synthetic V3
      loop peptides derived from three different HIV-1 strains were used as ligands to
      identify the cell surface counterreceptor, which may participate in the infection
      of HIV-1. Two different cell lines, Molt-4 and U937, and three V3 loop peptides
      derived from LAVELI, HTLV-IIIMN, and HTLV-IIIB strains were used. The binding of
      HTLV-IIIB-derived peptide to the cell surface was confirmed using 125I-labeled
      surface proteins of both cell lines. The relative molecular mass of the major
      radioactive band on the autoradiogram was 32-33 kDa in both cell lines. A protein
      was purified from the plasma membrane fraction of Molt-4 cells using affinity
      columns coupled with three different V3 loop peptides. Two major polypeptides (32
      and 33 kDa) were eluted from the affinity column. Size-exclusion chromatography
      showed that the protein migrated as a single peak with a molecular mass of 130
      kDa. These proteins were separated by reversed-phase chromatography, which
      indicated that the 32-kDa protein is more hydrophobic than the 33-kDa protein in
      Molt-4 cells. A similar but not identical 130-kDa protein with 32- and 33-kDa
      polypeptides were also purified from U937 cells. These findings indicate that HIV
      1 utilizes a tetrameric protein on the surface of Molt-4 and U937 cells on
      infection.

PMID- 7576913
TI  - Single basic amino acid substitutions at position 302 or 320 in the V3 domain of
      HIV type 1 are not sufficient to alter the antiviral activity of dextran sulfate
      and heparin.
AB  - The third variable domain (V3 domain) of the human immunodeficiency virus type 1
      (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively
      charged amino acid residues. We previously demonstrated that mutation of basic
      amino acid residues at position 303, 306, 309, 313, and 325 in the V3 domain of
      HIV-1 strain NL4-3 resulted in a dramatic elimination of both virus infectivity
      and syncytium-inducing ability. Mutations of arginine at position 302 to serine
      (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on
      infectivity for a panel of T cell lines tested. These mutations are located on
      opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the center of the V3
      domain. The R302S and K320Q mutations allowed us to determine if these basic
      residues are important for virus neutralization by polyanionic compounds. Dextran
      sulfate and heparin inhibited the cytopathogenicities of both mutants for MT-4
      cells, although their 50% antiviral effective doses were slightly higher than
      those required to achieve complete protection against wild-type HIV-1NL4-3
      replication. This result emphasizes that the basic amino acids of Arg302 and
      Lys320 are not essential for the inhibitory effect of dextran sulfate and heparin
      on HIV-1 infection.

PMID- 7576914
TI  - Direct interaction of complement factor H with the C1 domain of HIV type 1
      glycoprotein 120.
AB  - A protein that binds specifically to Env 105-119 (HEDIISLWDQSLKPC) was found in
      pools of normal human plasma when this peptide was used in affinity
      chromatography procedures. These samples represented the negative control in
      experiments aimed at the purification of putative human antibodies to the Env 105
      119 region from AIDS sera. In this article we describe the biochemical
      characterization of this protein, which turned out to be complement factor H
      (CFH). We propose a functional role for this protein in the complex, early steps
      of CD4-dependent HIV infection.

PMID- 7576916
TI  - Characterization of HIV type 1 from Romanian children: lack of correlation
      between V3 loop amino acid sequence and syncytium formation in MT-2 cells.
AB  - The biological properties and amino acid sequences of the third variable domain
      (V3 loop and flanking regions) of the env region of 34 HIV-1 isolates obtained
      from Romanian children were analyzed. Unambiguous nucleic acid sequences were
      obtained from 31 isolates. The derived V3 amino acid sequences were highly
      homologous (93-100%) and clustered with the HIV-1 subtype F Romanian consensus.
      Five of the 31 isolates presented a syncytium-inducing phenotype in MT-2 cells
      and established continuous viral replication in various CD4+ cell lines
      (rapid/high phenotype). The V3 sequence from one of these isolates showed a
      slightly lesser degree of homology with the consensus sequence. The presence of
      positively charged amino acids at positions 306 and 320 has been strongly
      associated with the ability to induce syncytia in MT-2 cells, whereas negatively
      or uncharged amino acids at these positions are present in non-syncytium-inducing
      isolates (slow/low phenotype). There was, however, no correlation between
      phenotype and amino acid sequence in the five syncytium-inducing isolates;
      negatively or uncharged amino acids were conserved at positions 306 and 320 for
      all 31 isolates in sequences obtained from PBMCs. A tendency toward a more
      positive net charge in the V3 loop of syncytium-inducing isolates was noted.
      These data confirm the recent observations that HIV-1 isolates from Romania not
      only cluster in subtype F, but also show a high degree of interpatient
      homogeneity in the V3 region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576915
TI  - Seroreactivity of analogous antigenic epitopes in glycoprotein 120 expressed in
      HIV-1 subtypes A, B, C, and D.
AB  - This article describes the impact of sequence variation on the distribution and
      seroreactivity of linear antigenic epitopes in gp120 encoded in new Ugandan HIV-1
      clones from subtypes A, C, and D, and in North American clones from the B
      subtype. A region of the env gene encoding the C2 to V5 domains was PCR amplified
      from the lysates of peripheral blood leukocytes or from short-term cultured
      isolates. Computer-assisted analyses were conducted on the amino acid sequences
      to determine the distribution of surface structures in gp120. Despite marked
      sequence diversity, eight analogous epitopes were predicted for all clades of the
      virus analyzed. Synthetic peptides comprising the putative principal neutralizing
      determinant E2[V3], and other B cell epitopes E3[V3-V4], E4[V3-V4], E7[C3], and
      E8[V5], from a seroprevalent Ugandan isolate, AUG06c, were tested in ELISA for
      antigenicity with sera from Uganda, New York, and Thailand. Variable magnitudes
      of seroreactivity were observed for all of the peptides tested. However, a
      significantly higher degree of serum cross-reactivity was detected with the V3
      loop peptide. ELISA reactivities of the same serum panel indicated that V3 loop
      peptides containing the apical residues GPGR (clones AUG06c and BRT3) or GPGQ
      (CUG045 and DUG044) were more antigenic and display extensive cross-reactivity as
      compared to analogous peptides comprising GLGQ (DUG23c), GQGQ (DUG042), or GPWG
      (BRT1). BETATURN analysis of the divergent V3 loop apical residues showed a good
      correlation of probable beta-turn occurrence with strong seroreactivity. These
      findings suggest that the major antigenic specificities in the divergent clades
      of HIV-1 are well conserved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7576917
TI  - Molecular characterization of human immunodeficiency virus type 1 isolates from
      Venezuela.
AB  - Eight HIV-1 isolates from Venezuela have been characterized by nucleotide
      sequencing of the entire reverse transcriptase (RT)- and surface glycoprotein (gp
      120)-coding regions. Average mutant frequencies were 2.5 x 10(-2) substitutions
      per nucleotide (s/nt) for the RT-coding region, and 10 x 10(-2) or 6.8 x 10(-2)
      s/nt for the gp120-coding region, depending on whether gaps introduced for
      optimal alignment were or were not, respectively, considered in the calculations.
      Phylogenetic trees were derived by maximum-likelihood, neighbor-joining, and
      maximum parsimony methods. In the trees derived from both RT- and gp120-coding
      regions, Venezuelan isolates cluster with subtype B viruses. However, the
      relative position of some of the isolates is considerably different in the two
      trees. Unique V3 loop amino acid sequences, not represented in the current
      database, have been identified among the Venezuelan isolates. In addition to
      representing the first molecular characterization of HIV-1 from Venezuela, the
      extensive genetic heterogeneity observed reinforces the interest in
      characterizing additional HIV-1 isolates worldwide for adequate vaccine design.

PMID- 7576918
TI  - Intrapatient variability of the human immunodeficiency virus type 2 envelope V3
      loop.
AB  - Studies of HIV-2 infection have shown lower rates of sexual and perinatal
      transmission and a prolonged incubation period to AIDS as compared to HIV-1. To
      evaluate the role of genetic variation in HIV pathogenesis, we studied
      intrapatient variability in the V3 loop of the HIV-2 envelope gene over time in
      five seropositive individuals. Proviral sequences derived from uncultured PBMC
      DNA (n = 102) demonstrated an average sequence heterogeneity within a sample of
      1.4% (0-4.1%). This was significantly lower than the V3 sequence heterogeneity
      observed in HIV-1, which can be as high as 6.1%. In HIV-2-seropositive healthy
      patients the average intrapatient nucleotide variability rate was 0.6% compared
      to 2.0% in patients with clinical AIDS. The lower rate of variability between HIV
      2 and HIV-1 is compatible with differences in transmission and pathogenesis of
      these two related viruses.

PMID- 7576920
TI  - Extraordinary high rate of HTLV type II seropositivity in intravenous drug
      abusers in south Vietnam.
AB  - Serum specimens (n = 1899) were assayed for infections with HTLV-I, HTLV-II, and
      HIV-1 in seven classified groups of normal healthy controls, children, pregnant
      women, prostitutes, intravenous drug abusers, patients under going hemodialysis,
      and hemophiliacs in South and North Vietnam. Surprisingly, 125 of 954 samples
      from South Vietnam exhibited seropositivity for HTLV-II and 119 of these belonged
      to the group of IVDAs (n = 200). The remaining six positives were a healthy
      control, a prostitute, two children, and two patients under going hemodialysis.
      Two IVDAs who were seropositive for HTLV-I and 10 of 15 seropositives for HIV-1
      were also positive for HTLV-II in this population. In contrast, no seropositives
      to any of the viruses were detected in the North Vietnamese samples (0 of 945).
      The HTLV-II-seropositive IVDAs exhibited increased seropositivity with age
      compared with HIV-1 seropositivity in the population, and there was no
      statistical relation between seropositivity for HTLV-II and HIV-1. The HTLV-IIs
      in South Vietnam IVDAs appeared, by subtype-specific peptide ELISA, to be a
      mixture of both subtypes a and b, with subtype a predominant. It seems possible
      that HTLV-II may have been introduced into this population from IVDAs from the
      United States during the Vietnam conflict, but in a period prior to, or early in,
      the introduction of HIV-1 to IVDAs.

PMID- 7576919
TI  - Nucleotide sequence and restriction fragment length polymorphism analysis of the
      long terminal repeat of human T cell leukemia virus type II.
AB  - Molecular studies have demonstrated the existence of two major subtypes of human
      T cell leukemia virus type II: HTLV-IIa and HTLV-IIb. In attempts to further
      classify this family of viruses we have carried out nucleotide sequence and
      restriction fragment length polymorphism (RFLP) analysis of the long terminal
      repeat (LTR), a region that has been shown in previous studies to have the
      greatest intra- and intersubtype genomic divergence. Analysis of the nucleotide
      sequences suggested the existence of distinct phylogenetic groups in each subtype
      and, on the basis of predicted differences in restriction endonuclease sites,
      RFLP analysis allowed the identification of four groups within the IIa subtype
      (a1-a4) and six within the IIb subtype (b1-b6). Nucleotide sequence analysis also
      suggested the possible existence of HTLV-II quasispecies. However, this appeared
      not to be significant, and preliminary studies suggest that these would not be
      expected to influence the results of RFLP analysis appreciably. The validity of
      the RFLP method was demonstrated in an analysis of 36 randomly chosen samples
      from HTLV-II seropositive blood donors from the New York City Blood Center, where
      it could be shown that all could be successfully classified. Moreover, the RFLP
      analysis correctly matched the viruses in donors and recipients of contaminated
      blood in four situations in which HTLV-II was inadvertently transmitted by
      transfusion. RFLP analysis of the LTR appears to be a rapid and reliable method
      by which to identify HTLV-II infection. This should prove useful in studies of
      the epidemiology and the characterization of viruses present both in
      nonindigenous and indigenous populations.

PMID- 7576921
TI  - Presence of the widespread subtype of HTLV-I in South Africa.

PMID- 7576922
TI  - Analysis of HTLV-I Env gene sequence from an Italian polytransfused patient:
      evidence for a Zairian HTLV-I in Sicily.

PMID- 7576923
TI  - HIV-1 gp120 sequences from a doubly infected drug user.

PMID- 7576924
TI  - Identification of HIV-1 subtype G from Uganda.

PMID- 7576925
TI  - Molecular cloning and characterization of a TAR-binding nuclear factor from T
      cells.
AB  - The TAt protein of the human immunodeficiency virus type 1 (HIV-1) activates the
      expression of viral mRNA through a cis-acting element in the LTR termed TAR. TAR
      RNA forms a stable stem-loop structure. Mutagenesis studies indicate that the
      stem structure, the primary sequence of the loop, and three unpaired bases in the
      stem (bulge) are important for Tat activation. Using the in vitro-transcribed TAR
      RNA as a probe, we have cloned a gene (TARBP-b) that encodes a TAR-binding
      protein from a cDNA expression library derived from Hut-78 cells. Expression of
      the 1.4-kb TARBP-b mRNA was observed in all mammalian cell lines tested. TARBP-b
      binds specifically to the bulge region of TAR RNA and trans-activates the HIV-1
      long terminal repeat in the presence of ptat and prev expression plasmids. These
      results suggest that TARBP-b contributes to tat-mediated trans-activation.

PMID- 7576926
TI  - Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959.
AB  - During replication of human immunodeficiency virus type 1 (HIV-1), proteolytic
      cleavage of Gag and Gag-Pol precursor proteins into different functional protein
      subunits is catalyzed by the viral proteinase, and this enzyme is the target of
      the antiviral proteinase inhibitor, Ro 31-8959. We investigated in vitro which
      HIV mutants with reduced sensitivity to Ro 31-8959 emerged during proteinase
      inhibition treatment; from three different HIV-1 strains, comparable progeny
      virus resistant to proteinase inhibitor were found, whereas the same experimental
      protocol detected no resistant HIV-2 mutants. Molecular analysis of the mutations
      underlying resistance revealed a multistep mechanism in which an amino acid
      exchange was common to all resistant isolates, and in all experiments preceded
      further exchanges at position 90 (leucine to methionine) and/or at position 54
      (isoleucine to valine). For wild-type strains the 90% inhibitory concentrations
      of Ro 31-8959 were close to 20 nM, whereas HIV-1 mutants with all 3 amino acid
      exchanges had more than 50-fold increased 90% inhibitory concentrations (above
      1000 nM). The primary event (Gly-48 to valine) occurs at the hinge of the flaps
      of the proteinase, thus hampering entry of the inhibitor to the active center and
      suggesting steric hindrance. Detailed knowledge of this stereotypic process could
      open inhibitor design, thus preventing conceivable escape of resistant virus on
      proteinase inhibitor action.

PMID- 7576928
TI  - Multifaceted consequences of anti-gp41 monoclonal antibody 2F5 binding to HIV
      type 1 virions.
AB  - A human monoclonal antibody (MAb) (2F5) neutralizing a variety of laboratory
      strains and clinical isolates of the human immunodeficiency virus type 1 (HIV-1)
      and binding to an epitope of the envelope glycoprotein gp41 encompassing the
      amino acid sequence ELDKWA has been described (Muster T et al., J Virol
      1993;67:6642-6647). It was suggested that an immunogen eliciting virus
      neutralizing antibodies having a specificity similar to that of MAb 2F5 should be
      considered as a component of HIV-1 vaccines. Efforts in this direction would
      benefit from understanding the mechanism whereby MAb 2F5 neutralizes the
      infectivity of HIV-1. The segment of gp41 encompassing residues ELDKWA has so far
      not been directly implicated in initiation of infection by HIV-1, suggesting that
      MAb 2F5 might affect other sites on HIV-1 envelope glycoproteins playing a role
      in virus entry into target cells. We provide here evidence that MAb 2F5 binding
      to HIV-1 virus particles decreases the accessibility or conformation of the gp41
      fusion domain and of gp120 domains, including the binding site for the CD4 cell
      receptor. These apparently indirect consequences of MAb 2F5 binding to HIV-1 are
      likely to account for or contribute to the virus-neutralizing activity of this
      MAb.

PMID- 7576927
TI  - Antivirals that target the amino-terminal domain of HIV type 1 glycoprotein 41.
AB  - Functional and structural studies were made to assess whether a class of
      antiviral agents targets the N-terminal domain of the glycoprotein 41,000 (gp41)
      of human immunodeficiency virus type 1 (HIV-1). Previous experiments have shown
      that the amino-terminal peptide (FP-I; 23 amino acids, residues 519-541) of HIV-1
      gp41 is cytolytic to both human erythrocytes (non-CD4+ cells) and Hut-78 cells
      (CD4+ lymphocytes). Accordingly, FP-I-induced hemolysis may be used as a
      surrogate assay for evaluating the role of the N-terminal gp41 domain in HIV-cell
      interactions. Here, we studied the blocking of FP-I-induced lysis of erythrocytes
      by the following anti-HIV agents: (1) IgG [i.e., anti-(518-541) IgG] raised to an
      immunoconjugate of Arg-FP-I, (2) apolipoprotein A-1 (apo A-1) and a peptide based
      on apo A-1, (3) dextran sulfate, (4) gp41 peptide (residues 637-666), and (5)
      anionic human serum albumins. Dose-response curves indicated that their relative
      potency in inhibiting FP-I-induced hemolysis was approximately correlated with
      their previously reported anti-HIV activity. Electron spin resonance (ESR)
      studies showed that FP-I spin labeled at the N-terminal alanine binds to anti
      (518-541) IgG, dextran sulfate, and anionic albumins. The high in vitro antiviral
      activity and low cytotoxicity of these agents suggest that blocking membrane-FP-I
      interactions offers a novel approach for AIDS therapy or prophylaxis.

PMID- 7576929
TI  - Syncytium formation in cultured human lymphoid tissue: fusion of implanted HIV
      glycoprotein 120/41-expressing cells with native CD4+ cells.
AB  - While glycoprotein gp120/41 clearly causes HIV-infected cells to form syncytia in
      monolayers and in suspension, there is unfortunately scant knowledge on syncytium
      formation in tissues. We implanted gp120/41-expressing cells labeled with
      fluorescent particles inside blocks of human lymphoid tissue kept in long-term
      histoculture. Observed by confocal microscopy, together with immunohistochemical
      and morphological analysis of implanted cells, more than one-third of these
      gp120/41-expressing cells fused with native CD4+ cells of the host tissue,
      yielding small (three to five nuclei) syncytia. Such widespread fusion of
      gp120/41-expressing cells in tissue in vitro, together with the finding of
      increased virulence of syncytium-inducing isolates of HIV, support the hypothesis
      that syncytium formation within lymph tissue of HIV-infected individuals
      contributes to AIDS pathogenesis. This system and the methods developed may
      provide a way to study HIV-infected cells inside the very tissue whose
      destruction may prevent immune system repopulation.

PMID- 7576931
TI  - Altered constitutive and stress-regulated heat shock protein 27 expression in HIV
      type 1-infected cell lines.

PMID- 7576930
TI  - Membrane-interactive phospholipids inhibit HIV type 1-induced cell fusion and
      surface gp160/gp120 binding to monoclonal antibody.
AB  - Membrane-interactive phospholipids (PLs), previously evaluated for activity
      against HIV-1 in vitro, are known to affect late steps in viral replication.
      Studies were done to determine the effects of PL analogs on post-translational
      processing of HIV-1 proteins, binding of viral surface gp160/gp120 to CD4
      receptor, and HIV-1-induced cell fusion. Results of this investigation indicated
      that PL alone (1-octadecanamido-2-ethoxypropyl-rac-3-phosphocholine, CP-51) and
      PL-AZT conjugate (1-octadecanamido-2-ethoxypropyl-rac-3-phospho-3'- azido-3'
      deoxythymidine, CP-92) have no effect on HIV-1-induced syntheses or processing of
      gp160/gp120, pr51, p24, or p17 (including myristoylation) in infected cells.
      Progeny HIV-1 particles made in CP-92-treated H9IIIB cells contained gp120, pr51,
      and p24; however, these virus particles had reduced capacity to bind to CD4+
      cells. Both CP-51 and CP-92 inhibited syncytium (cell fusion) formation between
      treated HIV-1-infected cells and uninfected CD4+ cells, and, they reduced HIV-1
      gp160/gp120 binding to CD4+ cells and monoclonal antibody. These results suggest
      that anti-HIV-1 activity of PL compounds involves alteration of cell surface
      membranes and viral envelopes. Phospholipid compounds are a novel class of
      membrane interactive compounds with potential use in blocking the spread of HIV-1
      infection and pathogenesis in AIDS.

PMID- 7576932
TI  - Local synthesis of IgG antibodies to HIV within the female and male genital
      tracts during asymptomatic and pre-AIDS stages of HIV infection.
AB  - Paired sera and cervicovaginal secretions or seminal fluids, obtained from HIV-1
      infected, clinically asymptomatic women (n = 41) and men (n = 12), were
      investigated in order to test the hypothesis of a local synthesis of IgG to HIV
      in the female and male reproductive tracts. Anti-gp41 + p24 IgG was evaluated by
      an IgG immunocapture assay, and anti-gp160 IgG by an indirect ELISA. Estimation
      of anti-HIV IgG-specific activities was carried out after ponderal determination
      of total IgG and evaluation of anti-HIV IgG activity. IgG to gp41 + p24, as well
      as IgG to gp160, were specifically detected in all sera, cervicovaginal
      secretions, and seminal fluid samples from all tested HIV-1-infected subjects.
      The mean specific activities of IgG to gp41 + p24 in cervicovaginal secretions
      and in seminal fluids were about 33-fold (in women) and 16-fold (in men) that of
      the corresponding sera; similarly, the mean specific activities of IgG to gp160
      in genital secretions were about 17-fold (in women) and 10-fold (in men) that of
      the corresponding sera. IgGs to HIV are constantly detected in genital secretions
      from HIV-1-infected subjects, and appear to be largely synthesized in situ within
      the genital tract of both genders.

PMID- 7576933
TI  - In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia.
AB  - OBJECTIVE: To determine the safety, tolerance, and hematological and virological
      effects of the recombinant hematopoietic growth factor interleukin 3 (IL-3) in
      HIV-1-infected individuals with cytopenia. DESIGN AND METHODS: A phase I single
      center trial was conducted with patients in cohorts of three receiving one of
      four dose levels of self-administered, subcutaneously injected IL-3 (0.5, 1.0,
      2.5, or 5.0 micrograms/kg/day). Toxicities, hematological effects, and
      virological effects were recorded. Viral studies included serum HIV p24 antigen
      levels, quantitative plasma and peripheral blood mononuclear cell cultures, and
      quantitative, competitive polymerase chain reaction of patient plasma. RESULTS:
      Increases in white blood cell counts (WBC) and absolute neutrophil counts (ANC)
      were noted at the higher dose levels while absolute eosinophil counts (AEC)
      increased in all patients. The percent changes in WBC from baseline ranged from
      52 to 309 and in ANC from 20 to 262 in the 2.5- and 5.0-micrograms/kg/day groups.
      The mean AEC change was 17-fold (range, 2- to 59-fold). Hemoglobin, hematocrit,
      platelets, and CD4 and CD8 counts were generally unaffected although individual
      patients demonstrated increases in hemoglobin and platelet levels. Toxicities
      were generally mild, but one patient developed a transient local erythematous
      rash at the sites of IL-3 injection which pathologically demonstrated
      hypersensitivity vasculitis. Of note, viral studies did not demonstrate any
      consistent changes in HIV-1 activity. CONCLUSION: These data demonstrate limited
      hematological effects of IL-3 monotherapy in HIV-1-infected patients with
      cytopenia. However, should IL-3 be incorporated into combination cytokine
      therapies for HIV disease, these data suggest that IL-3 does not enhance in vivo
      HIV-1 activity.

PMID- 7576934
TI  - T cell blastogenic responses to Toxoplasma gondii trophozoites among HIV-infected
      patients.
AB  - OBJECTIVE: To evaluate the cell-mediated immune response to Toxoplasma gondii (T.
      gondii) among HIV-infected patients. METHODS: Forty HIV-infected patients were
      studied. Of them, 35 had antibodies to T. gondii and 5 had not. Nine of 35
      patients with detectable serum Toxoplasma antibodies were classified as group A1
      (CDC 1993), 10 as group B2, 6 as group B3, and 10 as group C3. Peripheral blood
      mononuclear cells (PBMCs) were obtained by Ficoll-Hypaque gradient
      centrifugation. Living Toxoplasma gondii trophozoites, herpes simplex virus
      (HSV), tetanus toxoid, and phytohemoagglutinin (PHA) were used in standard
      proliferation assays. Toxoplasma-responding blasts were expanded and assayed for
      antigen specificity and HLA restriction by proliferation assays. T cell subsets
      were analyzed using two-color flow cytometry. RESULTS: Among patients with
      detectable Toxoplasma serum antibodies, significant PBMC proliferation in
      response to T. gondii trophozoites was observed in those classified in group A1
      or B2 but not in those in groups B3 and C3. Toxoplasma-induced blasts from five
      of six patients after 7 days of culture and from five patients after 15 days of
      culture proliferated in response to T. gondii in the presence of either
      autologous or allogeneic PBMCs as antigen-presenting cells (APCs) and/or also
      proliferated in response to HSV. The surface markers of T. gondii-induced blasts
      showed a variable percentage of CD4 and CD8 activated cells. CONCLUSIONS: T cell
      proliferative response to living trophozoites of T. gondii is lost only in
      patients with severe depletion of CD4 cells. PBMC proliferation was observed only
      in patients with previous T. gondii infection, but the T cell blasts generated
      showed a strong alloreactivity (proliferating in response to allogeneic
      irradiated PBMCs) and were apparently not antigen specific (proliferating also in
      response to HSV).

PMID- 7576936
TI  - Animal models recapitulate aspects of HIV/CNS disease.
AB  - Neurobehavioral and pathological data indicate that the central nervous system
      (CNS) becomes infected with HIV-1 soon after the virus enters the body. However,
      neuropathogenesis of HIV-1 infection is difficult to investigate because the
      brain parenchyma is not accessible to sampling during the course of AIDS. The
      second compartment of the CNS, cerebrospinal fluid (CSF), is accessible to
      sampling but how changes in the CSF relate to the changes in the parenchyma is
      poorly understood. Thus, knowledge of the neuropathogenesis of HIV-1 infection
      predominantly stems from either postmortem or in vitro studies. This raises the
      need for animal models of HIV infection of the CNS. Such models have been
      developed and are briefly reviewed here. The models faithfully recapitulate some
      aspects of the HIV/CNS disease. Appropriate neuropathological changes and
      neurobehavioral dysfunction (e.g., cognitive and motor deficits) occur in SIV
      infected macaques. Central sensory electrophysiological changes and sleep
      disturbances occur in FIV-infected cats. Infection of the brain and behavioral
      changes comparable to some of the changes seen in humans occur in mice infected
      with a mixture of murine leukemia viruses. Genetically immunodeficient mice
      (e.g., SCID) accept HIV-infected human organs and or cell grafts. Evidence
      summarized here indicates that these HuSCID animals undergo neuropathological
      changes similar to those observed in brains of individuals who died with AIDS.
      Thus, presently available animal models provide an opportunity to investigate
      HIV/CNS disease, and to develop and test therapeutic interventions to prevent or
      cure the disease.

PMID- 7576935
TI  - Defective natural killer cell cytotoxic activity in feline immunodeficiency virus
      infected cats.
AB  - Flow cytometry has been employed to study NK cell cytotoxic activity in cats
      infected with feline immunodeficiency virus. The results show that animals
      infected for 12 months or more have decreased levels of NK cell cytotoxic
      activity in their blood. The impairment could not be overcome by in vitro
      treatment of effector cells with interleukin 2. Additional results suggest that
      the NK cells of infected cats are defective, in that they are still able to bind
      to target cells but have a reduced ability to kill them.

PMID- 7576939
TI  - National Cancer Institute 1995 annual meeting, Laboratory of Tumor Cell Biology,
      Bethesda, Maryland, August 27-September 2, 1995. Abstracts.

PMID- 7576938
TI  - Partial nucleotide sequence analysis of the first case of human T lymphotropic
      virus type II from Australia.

PMID- 7576937
TI  - Multiple enhancer motifs in HIV type 1 strains from Ethiopia.

PMID- 7576940
TI  - Schwann cells in neuroblastoma.
AB  - Why should we consider Schwann cells when we are interested in the biology of
      neuroblastomas (NBs)? Although we are familiar with the term "stroma-rich" NB, we
      basically think of a favourable prognostic subgroup, histologically distinguished
      by the development of a prominent Schwann cell-stroma. According to current
      opinion on the maturation processes in NBs, the NB-associated Schwann cell is
      believed to represent a differentiation product of the NB cell, and we therefore
      do not envisage the Schwann cell as having any important role in NBs. However,
      our interest was raised after having realised that Schwann cells in NBs are
      normal cells, very likely attracted to the neoplastic neuroblasts. But what role
      does this cell play in these tumours? Can we still reduce the appearance of
      Schwann cells in NBs to an epi-phenomenon or is this cell population responsible
      for the differentiation of certain NBs? If so, will it be possible to use their
      strategies to induce differentiation of neuroblasts and so render them non
      aggressive, mature ganglionic cells? To shed light on the possible interactions
      between normal Schwann cells and NB cells, the maturation capacity of NBs and the
      genetic constitution of the two main cell populations in these tumours are
      briefly reviewed. Some data leading to the current view on the origin of the
      Schwann cells in NBs, and several physiological aspects of the Schwann cells,
      including normal neurone-Schwann cell interactions, are detailed.

PMID- 7576941
TI  - Biochemical evidence for a mature phenotype in morphologically poorly
      differentiated neuroblastomas with a favourable outcome.
AB  - Neuroblastoma is an embryonal tumour of the sympathetic nervous system with
      marked heterogeneity in terms of histological maturity and clinical course. A
      previous study revealed that high tumour levels of the csrc protein, particularly
      its neuronal isoform (pp60csrcN), correlated with favourable outcome. To test
      whether this feature reflects a higher degree of neuronal maturation in these
      tumours, an extended series (47 consecutive neuroblastomas and 10
      ganglioneuromas) were analysed for levels of csrc protein isoforms, neuron
      specific enolase, and synaptophysin. Immunoblotting and radioimmunoassay
      techniques were employed. The results were compared with conventional
      histological signs of neuronal maturation. High pp60csrcN levels were specific
      for prognostically favourable neuroblastomas and correlated with high neuronal
      marker levels. However, signs of histological maturation correlated poorly with
      these parameters. It is therefore concluded that low stage tumours are highly
      differentiated in biochemical terms despite their frequently immature histology.
      Furthermore, the clinical usefulness of these biochemical parameters as
      prognostic markers was compared with established parameters in a multivariate
      analysis. Stage 4 disease, MYCN amplification, and age above 18 months at
      diagnosis was the most powerful combination of variables found for predicting a
      poor outcome. As expected, none of the neuronal differentiation markers
      investigated could add to the prediction of aggressive disease when compared with
      this model. However, high expression of pp60csrcN appeared to be useful in
      predicting long-term survival in high stage infant neuroblastoma.

PMID- 7576942
TI  - Immunohistochemical detection of high-affinity nerve growth factor receptor in
      neuroblastoma.
AB  - High levels of mRNA (as assessed by northern blot) for the high-affinity nerve
      growth factor receptor (p140TRK) are predictive of favourable outcome in
      neuroblastoma. The feasibility of determining p140trk on frozen sections using a
      recently developed monoclonal antibody was evaluated, and immunohistochemical
      findings were compared to those obtained from northern blot analysis. Primary
      tumour samples from 28 untreated patients were quick frozen and an indirect
      immunofluorescence assay was performed on 4-microns acetone-fixed cryostat
      sections. 9 cases were positive with immunohistochemistry, and these were among
      the 15 cases also positive by northern blot. None of the cases negative by
      northern blot were positive with immunohistochemistry. The concordance rate was
      79% (P < 0.03), with a sensitivity of 60% and a specificity of 100%.
      Immunohistochemistry can thus be rather reliable for assessing p140trk
      expression, even when only very small amounts of tissue are available, such as
      with needle biopsy.

PMID- 7576943
TI  - Retinoic acid and cAMP differentially regulate human chromogranin A promoter
      activity during differentiation of neuroblastoma cells.
AB  - We report the first evidence that differential transcriptional regulation of
      human chromogranin A (CHGA) gene expression occurs during in vitro treatment of
      tumorigenic neuroblastoma (NB) cells with retinoic acid (5 microM) and/or
      dibutyryl-cAMP (1 mM). The CHGA gene encodes a tissue specific protein restricted
      to cells of the diffuse neuroendocrine system, but also widely expressed among NB
      tumours. We previously reported that CHGA as well as other neuroendocrine markers
      are modulated during NB differentiation in vitro. To investigate, at the
      molecular level, the mechanisms leading to NB tumour cell differentiation during
      the treatment with biologically active compounds, we sequenced and functionally
      characterised 2169 bp of a genomic DNA clone encompassing the 5' flanking region
      of the human CHGA gene. Computer-assisted analysis of the sequence revealed the
      presence of a cAMP responsive element at positions -56 to -49, and Sp1 binding
      sites at positions -181 to -176 and -216 to -210. Two novel 9 bp motifs, located
      at position -462 to -454 and -91 to -83 of the CHGA promoter were identified in
      the regulatory regions of two other neuroendocrine genes encoding for tyrosine
      hydroxylase and neuropeptide Y. In addition, in the first 1000 bp of the
      untranslated 5' region, we found the presence of several putative DNA binding
      sites of bHLH molecules, a protein family regulating tissue specific
      differentiation. Transient transfection experiments of chloramphenicol
      acetyltransferase (CAT) deletion constructs, showed the presence of an active
      promoter within the first 455 bp upstream from the start site. This region
      conferred tissue specific expression to a CAT reporter gene. In addition, the
      transcriptional activity of this fragment was modulated during the induction of
      differentiation of NB cells treated by retinoic acid and/or dibutyryl-cAMP. These
      observations provide preliminary data regarding CHGA transcriptional regulation
      in NB cells, and indicate that retinoic acid and cAMP activate distinct,
      apparently competitive, transcriptional pathways during NB cell differentiation.
      The molecular characterisation of the mechanisms regulating CHGA expression in
      tumour and normal neuroendocrine tissue could lead to the identification of novel
      molecules potentially relevant for future gene therapy of NB tumours.

PMID- 7576944
TI  - Differentiation and survival influences of growth factors in human neuroblastoma.
AB  - Human neuroblastoma cell lines are established from high-stage, highly malignant
      tumours. Despite this and the fact that these tumours are arrested at an early,
      immature stage, many cell lines have the capacity to undergo neuronal
      differentiation under proper growth conditions. One such cell line is the
      noradrenergic SH-SY5Y cell line. These cells can be induced to mature by a
      variety of modalities, resulting in different mature phenotypes. The use of this
      cell system as a model to study the stem cell character of neuroblastoma is
      reviewed and discussed. In particular, we focus on growth factor dependencies in
      the SH-SY5Y system, and compare that to the normal situation, i.e. growth factor
      control of sympathetic neuronal and neuroendocrine differentiation during human
      and rat embryogenesis.

PMID- 7576945
TI  - Proliferation and apoptosis in neuroblastoma: subdividing the mitosis
      karyorrhexis index.
AB  - The Shimada classification is a frequently used, histopathological classification
      system for neuroblastoma tumours. Tumours are classified as prognostically
      favourable or unfavourable based upon stroma content, degree of neuroblastic
      maturation and patient age at diagnosis. The mitosis-karyorrhexis index is
      introduced in this classification system, as the cellular density sum of mitotic
      and karyorrhectic cells in the tumour. The biological nature of karyorrhectic
      cells is uncertain, but a high mitosis-karyorrhexis index in stroma-poor tumours
      is an indicator of poor prognosis. In this study, neuroblastoma tumours were
      analysed for cell proliferation, using antiproliferating cell nuclear antigen
      (PCNA) immunohistochemistry, and apoptosis, by morphology and in situ end
      labelling of fragmented DNA. The karyorrhectic cells described in the Shimada
      classification were shown to be either proliferating or undergoing apoptosis. It
      is further shown that a high cellular density of proliferating cells correlates
      with poor prognosis, whereas a high density of apoptosis, in contrast, indicates
      favourable outcome.

PMID- 7576946
TI  - Cell death by oxidative stress and ascorbic acid regeneration in human
      neuroectodermal cell lines.
AB  - In this paper, we show that human neuroectodermal cells exposed to 1-5 mM
      hydrogen peroxide or 10 nM-1 mM ascorbate die by programmed cell death induced by
      oxidative stress. The cell death by peroxide occurs within 4 h and involves
      approximately 80% of B-mel melanoma cells, while ascorbate causes cell death of
      approximately 86% of B-mel cells within 24 h. SK-N-BE(2) neuroblastoma cells are
      more resistant, 32% and 43% cell death for peroxide and ascorbate, respectively.
      In all cases, cell death causes hypodiploic DNA staining, evaluated by flow
      cytometry. Both cell lines can efficiently metabolise ascorbate due to
      significant levels of NADH-dependent semidehydroascorbate reductase and
      glutathione-dependent dehydroascorbate reductase. The cell death observed
      suggests a pro-oxidant, rather than anti-oxidant, role for ascorbic acid at
      physiological concentrations under these experimental conditions.

PMID- 7576947
TI  - Effects of stem cell factor and other bone marrow-derived growth factors on the
      expression of adhesion molecules and proliferation of human neuroblastoma cells.
AB  - Metastasis in children with neuroblastoma (NB) is a poor prognostic factor
      despite intensive therapy. In the near future, stem cell factor (SCF) is likely
      to be used clinically to accelerate bone marrow (BM) recovery after high-dose
      chemotherapy in patients with advanced NB. The high frequency of BM metastases in
      NB could be secondary to BM-derived human growth factors (HGF) modulating the
      adhesion, secondary growth (or both) of circulating metastatic NB cells. To test
      this hypothesis, we studied the in vitro effects on NB cell lines grown in
      chemically defined medium of SCF, interleukin (IL)-1 beta, IL-3, IL-6, basic
      fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) used
      alone or in combination. The antigenic expression of NB-associated cell adhesion
      molecules (CAM) HLA class 1, intercellular CAM-1, neural-CAM and CD44 were
      assayed by monoclonal antibodies and flow cytometry, and DNA synthesis by 3H
      thymidine uptake. The expression of CAM was not modulated by SCF or other HGFs.
      An increase in thymidine uptake was induced by bFGF alone in IMR-32 cells, while
      SCF and other HGFs had no notable effect. Our results indicate that SCF and other
      BM-derived HGFs are unlikely to have a generalised effect on the expression of
      adhesion molecules by NB cells or proliferation. The clinical administration of
      recombinant human SCF to children with NB should be safe.

PMID- 7576949
TI  - Effect of retinoic acid on p21ras and regulators of its activity in
      neuroblastoma.
AB  - p21ras is a membrane-associated guanine nucleotide-binding protein with intrinsic
      GTPase activity. This protein is important in the regulation of cell growth and
      differentiation in a number of different cell types. Therefore, the aim of the
      present study was to examine the role of p21ras and regulators of its activity in
      the differentiation of neuroblastoma cells induced by retinoic acid (RA).
      Phosphorylation of p21ras is regulated by the GTPase activity of type I GAP120
      and neurofibromin. RA-induced differentiation of the two neuroblastoma cell lines
      SK-N-SH and IMR-32 was closely related to growth inhibition. Differentiation
      induced by RA resulted in an increase in both type I GAP120 and neurofibromin
      mRNAs. This increase was accompanied by a decrease in the activation of p21ras.
      These results suggest that, in neuroblastoma, activation of p21ras is not
      associated with RA-induced differentiation. However, the GTPase activating
      proteins type I GAP120 and neurofibromin may have effector functions in RA
      induced differentiation of neuroblastoma.

PMID- 7576948
TI  - CD44 expression and modulation on human neuroblastoma tumours and cell lines.
AB  - The human CD44 cell surface glycoprotein has been involved in a variety of
      functions including lymphocyte homing, extracellular cell matrix attachment and
      tumour metastasis. A large family of variants or isoforms, generated by
      alternative splicing of a single gene, has been reported to be involved in the
      malignant process, by conferring metastatic potential to non-metastatic cells.
      Neuroblastoma is a tumour characterised by an aggressive and metastatic behaviour
      in advanced stages, with amplification of the MYCN protooncogene. In this report,
      we show that the CD44 standard molecule was highly expressed in the majority of
      tumours of stages 1-3, in all stage 4s and ganglioneuromas, but only in a subset
      of stage 4 tumours. A lack of CD44 expression was observed in all MYCN amplified
      stage 4 tumours, thus demonstrating a highly significant inverse relationship
      between MYCN amplification and CD44 expression in neuroblastoma. In addition, the
      expression of 4 different CD44 isoforms was measured on all specimens and was
      always found to be negative. Using neuroblastoma cell lines and MYCN expressing
      transfectants, we show that CD44 expression by neuroblastoma cell lines is not
      directly related to MYCN amplification, but is associated to the stage of
      differentiation or lineage, and to the tumorigenic properties of the cells. In
      addition, CD44 expression can be upmodulated parallel to differentiation or
      maturation as induced by retinoic acid, bromodeoxyuridine or phorbol ester. In
      contrast, cytokines such as IFN gamma, TNF alpha, or growth factors such as bFGF,
      SCF and TGF beta were ineffective in modulating CD44 expression.

PMID- 7576950
TI  - Somatostatin and vasoactive intestinal peptide (VIP) in neuroblastoma and
      ganglioneuroma: chromatographic characterisation and release during surgery.
AB  - Neuroblastomas and ganglioneuromas frequently produce somatostatin (SOM) and
      vasoactive intestinal peptide (VIP), and elevated concentrations in tumour tissue
      are associated with favourable outcome. Both somatostatin and VIP have been shown
      to have an autocrine effect on tumour growth and differentiation in vitro, and
      VIP may cause clinical symptoms when released systemically. Using gel-permeation
      chromatography and specific radioimmunoassays, we further characterised
      somatostatin-like immunoreactivity (SOM-LI) and VIP-like immunoreactivity (VIP
      LI) in neuroblastoma and ganglioneuroma tumour tissue. The major part of SOM-LI
      and VIP-LI in both neuroblastoma and ganglioneuroma represents the biologically
      active forms SOM-28, SOM-14 and VIP-2, respectively. 21 children with
      neuroblastoma and ganglioneuroma were monitored with serial plasma samples during
      surgery. In 8 children with measurable concentrations of SOM-LI, all showed
      increased concentrations during tumour manipulation (P = 0.004) that subsequently
      decreased below preoperative levels in all but one case (P = 0.06). The only
      child presenting with diarrhoea showed the highest preoperative plasma VIP-LI in
      the study (54 pmol/l). 2 children with increased concentrations of VIP-LI
      preoperatively showed a rapid decrease after surgical tumour removal. These
      findings indicate a systemic release from the tumours. It is concluded that
      plasma and tumour tissue from children with neuroblastoma and ganglioneuroma
      contain biologically active molecular forms of somatostatin and vasoactive
      intestinal peptide. These peptides may bear significance both for specific
      symptoms in certain patients as well as influencing tumour growth and
      differentiation in vivo.

PMID- 7576951
TI  - Gene expression and neuroblastoma cell differentiation in response to retinoic
      acid: differential effects of 9-cis and all-trans retinoic acid.
AB  - Retinoic acid has considerable potential for the chemoprevention and chemotherapy
      of cancer. Neuroblastoma cells differentiate in response to retinoic acid in
      vitro, an observation that has led to clinical trials using either the 13-cis or
      all-trans isomers of retinoic acid. We review the effects of retinoic acid on
      neuroblastoma, and the potential involvement of nuclear retinoic acid receptors
      (RARs) and retinoid X receptors (RXRs). 9-cis retinoic acid is a ligand for RXRs,
      and we review recent data on the differential effects of 9-cis and all-trans
      retinoic acid on neuroblastoma differentiation and proliferation in vitro, and
      possible mechanisms of action via hetero- and homodimers of RARs and RXRs.
      Although there is uncertainty whether or not 9-cis retinoic acid produces its
      biological effects primarily via RXR homodimers, in vitro data suggest that this
      isomer of retinoic acid or stable analogues may have considerable potential for
      the treatment of resistant, disseminated neuroblastoma.

PMID- 7576952
TI  - Cytotoxicity of paclitaxel and docetaxel in human neuroblastoma cell lines.
AB  - Taxanes are an important new class of anticancer agents that inhibit cell
      division by the unique mechanism of increasing the rate of microtubule assembly
      and preventing microtubule depolymerisation. Using the colony inhibition assay,
      we compared the cytotoxicity of paclitaxel and docetaxel in three human
      neuroblastoma (NB) cell lines, SH-SY5Y, BE(2)M17 and CHP100. Different exposure
      times (3, 6, 12, 24, 48 and 72 h) and different concentrations ranging from 0.1
      nM to 10 microM were tested. Both paclitaxel and docetaxel show antineoplastic
      activity in human NB cell lines. Taxanes' antitumour activity varied among the
      different cell lines, CHP100 being the most sensitive and SH-SY5Y the least
      sensitive. Paclitaxel cytotoxicity appears schedule-dependent, with marked cell
      kill observed only for exposures of 24 h or longer. Docetaxel cytotoxicity was
      dependent upon prolonged exposure only in the SH-SY5Y cell line, while an
      exposure time of 3-6 h resulted in exponential cell kill in the other two cell
      lines. Docetaxel was more cytotoxic than paclitaxel with a mean ratio of
      (paclitaxel/docetaxel) IC50 values ranging from 2 to 11. For both taxanes, we
      observed good correlation between cytotoxic effect and percentage of cells
      blocked in G2/M phase. A cytotoxic effect occurred at concentrations comparable
      with those achieved in the plasma of patients treated with these agents in
      initial clinical trials. The full potential of prolonged infusion or repeated
      daily administrations of taxanes should be explored in clinical studies, and
      responses to taxanes in neuroblastoma should be assessed in paediatric phase II
      studies.

PMID- 7576954
TI  - Molecular basis for heterogeneity in human neuroblastomas.
AB  - Neuroblastomas demonstrate both clinical and biological heterogeneity. We have
      proposed that neuroblastomas may be classified in three genetically distinct
      subtypes, based on cytogenetic and molecular analysis. The first comprises those
      with hyperdiploid or triploid modal karyotypes (or compatible DNA content by flow
      cytometry), 1p LOH and MYCN amplification are absent, and TRKA expression is
      high. These patients are likely to be infants with low stages of disease (stages
      1, 2, or 4S by the International Neuroblastoma Staging System), and they have a
      very favourable outcome (> 90% cure). The second group consists of tumours that
      generally have a near diploid or tetraploid modal chromosome number or DNA
      content but lack MYCN amplification. They usually have 1p allelic loss, 14q
      allelic loss or other structural changes, and TRKA expression is usually low.
      These patients are generally older with advanced stages of disease (stages 3 or
      4), and they have a slowly progressive course, with a cure rate of 25-50%. The
      third group is characterised by tumours with MYCN amplification. These tumours
      are generally near diploid or tetraploid, with 1p allelic loss, and low or absent
      TRKA expression. The patients are usually between 1 and 5 years of age with
      advanced stages of disease, and they have a very poor prognosis (< 5%). It
      remains to be determined if tumours in one group ever evolve into a less
      unfavourable group, but current evidence suggests that they are distinct
      genetically. The identification of the oncogenes, suppressor genes and growth
      factor receptor pathways involved in neuroblastomas has provided great insight
      into the mechanisms of malignant transformation and progression, and ultimately
      they may provide the targets for future therapy.

PMID- 7576953
TI  - Gene expression and protein localisation of calcyclin, a calcium-binding protein
      of the S-100 family in fresh neuroblastomas.
AB  - Calcyclin gene, a Ca(2+)-binding protein with homology to S-100, has been found
      to be expressed at different levels in leukaemic cells and in other tumour cells.
      We recently reported the expression of the gene in human neuroblastoma (NB) cell
      lines, and suggested a possible role of calcyclin in cell differentiation. To
      extend our findings, we investigated the expression of the gene in NB cells
      induced to differentiate by retinoic acid (RA), using the reverse transcriptase
      polymerase chain reaction (RT-PCR) technique. Time-course experiments employing
      LA-N-5 cells showed that calcyclin mRNA appeared 2 h after RA treatment, long
      before the cells were blocked in the G1 cell-cycle phase and before the neurite
      like structures outgrew from the cell bodies. This suggests the involvement of
      the gene in the early phase of cell differentiation. Furthermore, we investigated
      mRNA expression in a series of fresh neuroblastomas. NB tumours showed a
      heterogeneous pattern of calcyclin expression, although calcyclin seemed to be
      expressed more frequently in cases with a favourable Shimada histology. We also
      studied the expression of the protein in formalin fixed and paraffin embedded
      tissues, by using a specific anticalcyclin antibody. The protein was detected in
      stromal cells which characterise a more mature histological type, and in nerve
      sheaths, whereas neuroblasts were negative. The tissue that expressed calcyclin
      protein showed a Schwann-like differentiation and, unlike S-100 protein,
      calcyclin was expressed in the perineurium.

PMID- 7576955
TI  - Regression and progression in neuroblastoma. Does genetics predict tumour
      behaviour?
AB  - Neuroblastoma (NB) is a heterogeneous disease. The clinical course may range from
      spontaneous regression and maturation to very aggressive behaviour. Stage 4s is a
      unique subcategory of NB, generally associated with good prognosis, despite skin
      and/or liver involvement and the frequent presence of tumour cells in the bone
      marrow. Another type of NB is the locally invasive tumour without bone and bone
      marrow involvement which can also have a good prognosis, irrespective of lymph
      node involvement. Unfortunately, there is only limited biological information on
      such tumours which have not been treated with cytotoxic therapy despite lymph
      node involvement, residual tumour mass after surgery and/or bone marrow
      infiltration. In order to find specific genetic changes common to NBs with a
      benign clinical course, we studied the genetic abnormalities of these tumours and
      compared them with highly aggressive tumours. We analysed a series of 54
      localised and stage 4s tumours by means of in situ hybridisation performed on
      fresh cells or on paraffin embedded tissues. In addition, we performed classical
      cytogenetics, Southern blotting and PCR analysis on fresh tumour tissue. The
      majority of patients had been treated with surgery alone, and in a number of
      patients tumour resection was incomplete. Deletions at 1p36 and amplifications of
      the MYCN oncogene were absent, and diploidy or tetraploidy were not seen in any
      case, with residual localised tumours possessing a favourable outcome.
      Unexpectedly, one patient with a tetraploid 4s tumour without any genetic
      structural changes not receiving any cytotoxic treatment, did well.
      Interestingly, this genetic spectrum contrasted with that of progressing tumours,
      in which most had genetic aberrations, the deletion at 1p36 being the most common
      event. These data, although limited, suggest that an intact 1p36 (recognised by
      D1Z2), the absence of MYCN amplification and near-triploidy (at least in
      localised tumours), represent prerequisites for spontaneous regression and/or
      maturation.

PMID- 7576960
TI  - Molecular cytogenetic analysis of 1;17 translocations in neuroblastoma.
AB  - Loss of chromosome 1 short arm material, resulting from terminal deletions or
      unbalanced translocations, is a frequent finding in advanced neuroblastoma. In
      translocations, often relatively small portions of a second chromosome are
      translocated to the chromosome 1 short arm. The chromosomal origin of this
      translocated material could often not be identified using banding analysis only.
      Recent studies, applying fluorescent in situ hybridisation, showed that in the
      majority of these translocations, chromosome 17 is involved. In this study, the
      nonrandom occurrence of unbalanced 1;17 translocations is further supported by
      their presence in 3/7 neuroblastoma cell lines. Analysis of the 1p breakpoints
      extends our earlier observation of breakpoint heterogeneity. A similar scattering
      of 17q breakpoints was observed. The 1p and 17q breakpoints of the constitutional
      1;17 translocation did not coincide with any of the 1;17 translocation
      breakpoints found in neuroblastoma cell lines. Cell lines, not containing 1;17
      translocations, contained other chromosome 17 rearrangements. As a result, extra
      copies of 17q are found in all cell lines, suggesting a role for genes on 17q in
      neuroblastoma development. The possible significance of 1;17 translocations in
      neuroblastoma is discussed.

PMID- 7576957
TI  - Cytogenetic evolution of MYCN and MDM2 amplification in the neuroblastoma LS
      tumour and its cell line.
AB  - Amplification of the MYCN gene is frequently seen either in extrachromosomal
      double minutes (DMs) or in homogeneously staining regions (HSRs) of aggressively
      growing neuroblastomas. Total genomic DNA from cell line LS, from early passages
      of the same line and from original tumour material was biotinylated and
      hybridised to metaphase chromosomes of normal human lymphocytes. The reverse
      genomic hybridisation revealed the amplified DNA to be derived both from
      chromosome 2p23-24, which is the position of MYCN, and from chromosome 12 band
      q13-14. The MDM2 gene, located at 12q13-14, was found amplified both in early and
      late passages of LS, in addition to amplified MYCN. Amplification units of MYCN
      and MDM2 appear first to develop within DMs, which then integrate into different
      chromosomes to develop to HSRs.

PMID- 7576959
TI  - Reciprocal translocation at 1p36.2/D1S160 in a neuroblastoma cell line: isolation
      of a YAC clone at the break.
AB  - Band 1p36.1-1p36.2 is frequently involved in chromosomal aberrations of
      neuroblastoma cells, and therefore thought to harbour genetic information which
      may be involved in tumorigenesis. To map this putative neuroblastoma locus, we
      screened neuroblastoma cell lines for reciprocal translocations at 1p36.1-2 which
      may signal the site of an affected gene. We identified a reciprocal 1;15
      translocation in cell line NGP by fluorescence in situ hybridisation (FISH). As a
      strategy to clone the translocation breakpoint, we isolated yeast artificial
      chromosomes (YACs) specific for loci at 1p36. Screening of cell line NGP by FISH
      identified a YAC, 1050 kbp in size, which hybridised to both derivative 1;15 and
      15;1 chromosomes. We conclude that this YAC, which maps to D1S160, covers the
      break. This chromosomal position is within the smallest region of overlap (SRO)
      found in neuroblastoma tumours and within the region of a constitutional
      interstitial deletion of a neuroblastoma patient. The YAC we describe here should
      serve as a DNA source for gene cloning approaches towards the isolation of
      candidates for the putative neuroblastoma suppressor gene.

PMID- 7576956
TI  - The mycN/max protein complex in neuroblastoma. Short review.
AB  - The oncogenic activation by amplification of the MYCN gene is frequently observed
      in human neuroblastomas and occasionally in other tumours with neuronal
      qualities. As a consequence of amplification, elevated levels of the mycN protein
      are expressed. mycN contains a C-terminal basic region (BR) that can bind to DNA,
      and a helix-loop-helix (HLH)-leucine zipper (Zip) domain, which is responsible
      for the physical interaction with another HLH-Zip protein, max. This principle
      structure is conserved among all members of the MYC gene family. The resulting
      dimers can bind to the DNA sequence CACGTG. The mycN protein, but not max,
      contains, near the N-terminus, a region conferring the ability to activate the
      transcription of genes. mycN/max heterodimers probably activate and max/max
      homodimers repress transcription of, as yet, unidentified target genes. In
      neuroblastoma cells, where mycN is deregulated, the balanced interaction of BR
      HLH-Zip proteins is probably perturbed, and, therefore, genes controlled by mycN
      might be abnormally expressed and thereby alter normal cell growth with the
      consequence of tumorigenesis.

PMID- 7576961
TI  - A multiplex PCR assay for routine evaluation of deletion of the short arm of
      chromosome 1 in neuroblastoma.
AB  - Deletions of the short arm of chromosome 1 (1p) are frequent alterations in
      neuroblastoma. Although a consensus region of deletion has been mapped to
      chromosome subband 1p36, recent studies suggest that several distinct loci on
      this chromosome may be involved in neuroblastoma. Moreover, different patterns of
      deletion might be associated with different clinical and biological
      characteristics of the tumours. These findings emphasise the importance of
      assessing the localisation and the extent of the deletions in neuroblastoma. We
      developed a technique which allows analysis of loss of heterozygosity at multiple
      loci on 1p in a single step, making use of a multiplex PCR method. Primers
      specific for six microsatellite loci mapped in the different regions of interest
      on 1p were used for simultaneous amplification of DNA, and loss of heterozygosity
      was determined after separation of the alleles by denaturing polyacrylamide gel
      electrophoresis. This technique enables a simple analysis of the position and
      extent of 1p deletions, and can be used for routine evaluation of 1p status in
      neuroblastoma.

PMID- 7576958
TI  - Characterisation of the chromosome breakpoints in a patient with a constitutional
      translocation t(1;17)(p36.31-p36.13;q11.2-q12) and neuroblastoma.
AB  - Cytogenetic and molecular studies in neuroblastoma suggest the presence of a
      tumour suppressor gene at the distal chromosome band 1p36. Previously, we
      hypothesised that a constitutional translocation involving the region 1p36
      [t(1;17)(p36;q12-q21)] in a patient with neuroblastoma predisposed him to tumour
      development. Here we report the molecular delineation of the translocation
      breakpoints. Somatic cell hybrids containing the derivative chromosomes were used
      to determine the position of chromosome 1p and 17q DNA probes respective to the
      breakpoints using fluorescence in situ hybridisation. The 1p breakpoint was
      localised between the PND and D1S56 loci. The chromosome 17q breakpoint is
      flanked by NF1 and SCYA7, as proximal and distal marker, respectively. We
      redefined the translocation as t(1;17)(p36.31-13;q11.2-q12). The identification
      of flanking markers of the breakpoints is a prerequisite for breakpoint cloning
      and identification of a putative neuroblastoma suppressor gene.

PMID- 7576962
TI  - 1p36: every subband a suppressor?

PMID- 7576963
TI  - Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and
      CD44 expression as prognostic factors in neuroblastoma.
AB  - A comparison of the prognostic impact of five molecular variables in a large
      series was made, including tests of their nonrandom association and multivariate
      analysis. Molecular data were available for 377 patients and MYCN amplification,
      cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA
      ploidy and CD44 expression were investigated. Their interdependence and influence
      on event-free survival was tested uni- and multivariately using Pearson's chi 2
      test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN
      amplification was present in 18% (58/322) of cases and predicted poorer prognosis
      in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease.
      CD44 expression was found in 86% (127/148) of cases, and was a marker for
      favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P
      = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and
      indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA
      ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value.
      Most factors of prognostic significance were associated with each other. By
      multivariate analysis, MYCN was selected as the only relevant factor. Risk
      estimation of high discriminating power is, therefore, possible for patients with
      localised and metastatic neuroblastoma using stage and MYCN.

PMID- 7576965
TI  - Differentiation and prognosis of neuroblastoma in correlation to the expression
      of CD44s.
AB  - Cell-cell and cell-extracellular matrix interactions mediated by cell adhesion
      molecules (for example CD44) play an important role in the cascade of metastasis
      and the progression of human malignant tumours. The most important aim of this
      review was, on the basis of our results and the literature, to show the
      correlation between the expression of CD44s and differentiation and prognosis of
      neuroblastoma. Surprisingly and in contrast to most other malignant tumours,
      neuroblastomas exhibited an inverse correlation between CD44s expression and
      tumour progression. It can be stated that CD44s is a prognostic marker in
      neuroblastoma which correlates significantly with the grade of tumour cell
      differentiation, but not with clinical stage. Moreover, there exists a
      statistically significant correlation between MYCN oncogene amplification and the
      lack of CD44s expression.

PMID- 7576966
TI  - Early clinical evaluation of neuroblastoma cell detection by reverse
      transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA.
AB  - Disseminating disease in neuroblastoma is of considerable clinical importance.
      Detection of circulating neuroblastoma cells using tyrosine hydroxylase (TH) as a
      tissue-specific target for reverse transcriptase-polymerase chain reaction has
      proved to be a sensitive and specific method for the detection of contaminating
      tumour cells in peripheral blood. The aim of this study was to report the early
      clinical observations made using this technology in neuroblastoma patient blood
      samples. A strong association was found between the detection of neuroblastoma
      cells in circulation with the detection of neuroblastoma in bone marrow. This
      method may be of use to monitor disease status and identify early signs of
      relapse in clinically disease-free patients. These results show that RT-PCR
      detection of TH mRNA is a relatively noninvasive, sensitive method for the
      detection of circulating tumour cells in neuroblastoma patients.

PMID- 7576964
TI  - Evaluation of CD44 prognostic value in neuroblastoma: comparison with the other
      prognostic factors.
AB  - CD44 gene products are potential markers of aggressiveness in different tumour
      models, a result which prompted us to study clinical neuroblastoma (NB)
      specimens. CD44 expression was determined by immunostaining of 52 tumour samples
      from newly diagnosed NB with a monoclonal antibody (J173) directed against an
      epitope common to all CD44 isoforms. CD44 immunoreactivity was detected in 37 of
      the tumours (71%). CD44 was expressed in all 22 NBs with favourable prognoses
      (stages 1, 2 or 4S), but only 50% (15/30) of advanced NB (stages 3 and 4) (P <
      10(-4)), suggesting that the absence, rather than the overexpression, of CD44 is
      a signal of tumour aggressiveness. The cumulative progression-free survival was
      significantly longer in patients with CD44 positive tumours compared with
      patients with CD44 negative tumours (P < 10(-5)). More importantly, progression
      free survival was also significantly higher in CD44 positive patients within the
      high-risk group (P < 0.01). In univariate analysis, we tested the prognostic
      value of tumour expression of CD44 in comparison with tumour stage, age, tumour
      histology, and presence or absence of amplification of the MYCN protooncogene.
      All five measures had significant prognostic value. The expression of CD44 and
      the absence of MYCN amplification were the most powerful predictors of a
      favourable outcome. In a multivariate analysis of these measures, CD44 expression
      and tumour stage were the only independent prognostic factors for the prediction
      of patient survival. NB is the first clinical model described in which tumour
      aggressiveness correlates with repression rather than stimulation of CD44
      expression. We recommend the use of CD44 as an additional biological marker in
      the initial staging of NB.

PMID- 7576968
TI  - Genetic alterations associated with metastatic dissemination and chemoresistance
      in neuroblastoma.
AB  - Knowledge about genetic alterations specific to the metastatic process and
      chemoresistance in neuroblastoma is progressing steadily. Low or no CD44
      expression, increased NM23 expression and specific mutations of the 5' coding
      regions of NM23 are distinct features of aggressive, metastatic neuroblastoma.
      MYCN down-regulates Class I HLA antigen expression in many neuroblastoma cell
      lines and, in turn, may be regulated by a suppressor gene. The MYCN amplified
      human neuroblastoma cell line, IGR-N-91, established in vitro, metastasises in
      the nude mouse and has exhibited co-activation of MYCN and PGY1, resulting from
      direct activation of the oncoprotein on the PGY1 promoter. In this model, the
      MYCN product activates angiogenesis, the dissemination process and
      chemoresistance via specific genes (PGY1 and GST3). MYCN, like the BCL-2 and TP53
      products, may also play a key role in apoptosis. The implication of these genes
      in the potential for metastasis and chemoresistance in neuroblastoma is
      discussed.

PMID- 7576967
TI  - Pancreastatin immunoreactivity in favourable childhood neuroblastoma and
      ganglioneuroma.
AB  - Neuroblastoma and its benign counterpart, ganglioneuroma, are tumours of the
      sympathetic nervous system, and known to produce and release various regulatory
      peptides. In this study, pancreastatin, a 52 amino acid regulatory peptide
      derived from chromogranin A, was analysed in plasma and tumour tissue from 15
      children with neuroblastoma and one with ganglioneuroma. Detectable pancreastatin
      immunoreactivity (> 1.9 pmol/l) was found in plasma in 13 of 15 children with
      highest concentrations in samples from children with favourable outcome (P <
      0.05). In tumour tissue, non-metastatic tumours showed higher concentrations of
      pancreastatin immunoreactivity (P < 0.05). However, the highest concentrations
      were detected in tumours from children with favourable prognosis, regardless of
      clinical stage at presentation (P < 0.01). Serial plasma samples from one child
      with neuroblastoma and one with ganglioneuroma were investigated and showed
      significant systemic release of pancreastatin immunoreactivity during surgical
      manipulation of tumours with high pancreastatin concentrations. It is concluded
      that pancreastatin immunoreactivity may be detected in plasma samples and tumour
      extracts from children with neuroblastoma and ganglioneuroma. Systemic release
      during surgery implied tumour origin of elevated plasma pancreastatin.
      Furthermore, higher pancreastatin concentrations correlate with tumour
      differentiation, localised clinical stage and a favourable outcome for children
      with these tumours. It is suggested that pancreastatin in plasma and tumour
      tissue may be utilised as a marker indicating favourable tumour behaviour.

PMID- 7576969
TI  - Neuroblastoma mass screening: the arguments for and against.
AB  - Neuroblastoma is the second commonest malignancy in childhood. The prognosis of
      the disease is largely dependent on the extension of the tumour at diagnosis. For
      disseminated disease the survival rate is very low. The question as to whether
      mass screening in infants can improve the prognosis of the disease was first
      addressed in Japan more than 20 years ago. Since then, more than 7 million
      children have been screened in Japan and over 650 cases of neuroblastoma have
      been detected. However, the available data are compromised by an inadequate
      cancer registry and conclude that screening at 6 months of age seems to double
      the incidence of neuroblastoma. This result has been verified by a Canadian study
      conducted from 1989 to 1994 in the province of Quebec. The incidence of
      neuroblastoma appeared to have tripled, and there was no decrease in the rate of
      advanced disease. Mass screening pilot studies have also been conducted in the
      U.K., France, Austria, Australia, U.S.A., Italy, Norway and Germany. Analysis of
      the results shows that neuroblastoma screening before the age of 6 months is
      feasible, but no significant reduction in mortality could be shown until now.
      Moreover, most of the cases diagnosed by screening have favourable biological
      markers. Only a few with unfavourable parameters, such as amplification of proto
      oncogene MYCN, diploidy and/or del 1p36 could be detected. A screening programme
      that includes 1.25-2 million screened and unscreened children at 1 year of age
      monitored by an almost complete national cancer registry should show whether mass
      screening for early detection of neuroblastoma is worthwhile.

PMID- 7576970
TI  - Clinical strategies for the treatment of neuroblastoma.
AB  - Neuroblastoma is the most common solid extracranial tumour in childhood. In spite
      of intensive efforts of clinicians and scientists the prognosis for advanced
      disease is still poor. This paper presents a short review of the state-of-the-art
      in conventional treatment including surgery, chemotherapy, and radiation. This is
      followed by a review of the treatment attempts with high dose chemotherapy
      followed by autologous bone marrow or stem cell transplantation. One of the main
      problems with this approach is the contaminating tumour cells. Finally the
      various immunotherapeutic strategies are summarised which are used to remove
      minimal residual disease. Later, our new approach, combining various treatment
      modalities, is described.

PMID- 7576972
TI  - Enhanced tumour uptake and in vitro radiotoxicity of no-carrier-added [131I]meta
      iodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma.
AB  - In vitro and in vivo neuroblastoma models were used to determine whether
      improvements in tumour targeting in vivo and therapeutic efficacy in vitro could
      result from the use of no-carrier-added (n.c.a.) [131I]MIBG. Results were
      compared with use of the conventional therapy MIBG preparation (ex. [131I]MIBG)
      of lower specific activity which is produced by iodide exchange reaction. The
      efficacy of n.c.a. [131I]MIBG was compared with that of [131I]MIBG over a range
      of specific activities by the assessment of neuroblastoma spheroid growth delay.
      Whereas n.c.a. [131I]MIBG at a radioactivity concentration of 2 MBq/ml prevented
      the regrowth of 84% of spheroids, toxicity was significantly reduced by the
      addition of non-radiolabelled MIBG to the incubation medium. The time-dependent
      biodistribution of n.c.a. [131I]MIBG in nude mice bearing human neuroblastoma
      xenografts was compared with that of the conventional therapy
      radiopharmaceutical. The n.c.a. agent gave improved tumour uptake but also
      significantly greater accumulation in normal tissues known to accumulate MIBG
      such as heart, adrenal and skin. However, uptake and retention in the blood was
      unaltered. For all tissues examined, the 3-day calculations were undertaken to
      predict organ to tumour dose ratios which would result in human neuroblastoma
      patients with each of the [131I]MIBG preparations. These results suggest that
      significant therapeutic gain may be achieved by the use of n.c.a. [131I]MIBG as a
      treatment agent in neuroblastoma. neuroblastoma.

PMID- 7576971
TI  - Role of myeloablative therapy in improved outcome for high risk neuroblastoma:
      review of recent Children's Cancer Group results.
AB  - The use of new strategies for dose intensification using peripheral blood stem
      cell or autologous purged bone marrow rescue has raised expectations for cure in
      advanced neuroblastoma, although conflicting reports exist regarding the efficacy
      of these approaches. Using risk groups based on both biological and clinical
      staging, the Children's Cancer Group (CCG) has conducted a series of pilot
      studies to test new induction, consolidation and myeloablative regimens to
      attempt to improve outcome. We summarise below the outcome and prognostic factor
      analysis for the pilot chemotherapy trial, CCG-(CCG-321P2), and the use of high
      dose myeloablative chemoradiotherapy with allogeneic (CCG-321P1) or autologous
      purged bone marrow rescue (CCG-321P3) for high risk neuroblastoma patients who
      were progression-free at the end of induction chemotherapy. After autologous bone
      marrow transplantation (ABMT), progression-free survival (PFS) at 4 years was 38%
      (median follow-up 4 years). Prognostic factors for relapse after ABMT included
      pre-BMT disease status, bone marrow tumour content at harvest, extent of primary
      resection at diagnosis, and time to ABMT. MYCN amplification, age, stage, and pre
      BMT myeloablative regimen were not significant. Allogeneic BMT did not have a
      better outcome than ABMT. In a retrospective, non-randomised comparison of ABMT
      and chemotherapy, there was a significant difference in PFS for stage IV
      patients. High risk subgroups possibly benefiting from ABMT could be identified,
      including those with tumour MYCN amplification, over 2 years at diagnosis, and
      those not in complete remission at the end of induction. A randomised prospective
      trial comparing myeloablative therapy with ABMT to continuous infusion
      consolidation chemotherapy is currently underway in CCG to determine the relative
      benefit.

PMID- 7576974
TI  - Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine
      transporters in neuroblastoma cell lines: correlations to meta
      iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression.
AB  - Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in
      scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently,
      it has been demonstrated that MIBG is incorporated into neuroblastoma cells by
      the noradrenaline transporter. In vitro experiments on SK-N-SH human
      neuroblastoma cells performed in the present study showed that uptake of MIBG is
      inhibited by noradrenaline, more so by dopamine and to a lesser extent, by
      serotonin, indicating that the respective transporters may also contribute to
      MIBG uptake. However, neither dopamine nor serotonin transporter gene expression
      was detected. Noradrenaline transporter gene expression was found in 4 of 6
      investigated cell lines, which correlated with specific MIBG uptake. Furthermore,
      an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene
      expression, the key regulatory enzyme of catecholamine synthesis, was observed.
      These data show that MIBG is specifically incorporated only in neuroblastoma
      cells in which there is noradrenaline transporter gene expression. Furthermore,
      the catecholamine status in neuroblastoma cells is regulated by a coordinate
      expression of the key elements of catecholamine synthesis and reuptake systems.

PMID- 7576973
TI  - Meta-iodobenzylguanidine (MIBG) inhibits malate and succinate driven
      mitochondrial ATP synthesis in the human neuroblastoma cell line SK-N-BE(2c).
AB  - In this paper, we report on our studies of the effects of MIBG, a structural
      analogue of norepinephrine, on SK-N-BE(2c) cells. In micromolar concentrations,
      MIBG caused almost complete inhibition of the proliferation of SK-N-BE(2c) cells.
      In intact SK-N-BE(2c) cells, addition of MIBG led to a decrease of the ATP to ADP
      ratio. A progressive increase of the lactate to pyruvate ratio (due to increased
      lactate production) was observed after incubation of the cells with glucose and
      increasing concentrations of MIBG. In cells treated with digitonin, MIBG
      inhibited malate driven ATP synthesis. Comparable inhibition of ATP synthesis
      with succinate as a substrate required higher concentrations of MIBG. These
      results indicate that, apart from inhibition of complex I, MIBG was capable of
      inhibiting at least one other complex of the respiratory chain. Although maximal
      inhibition of ATP synthesis was observed at a concentration of 10 microM, optimal
      inhibition of cell proliferation occurred at a MIBG concentration > 25 microM.
      This suggests that MIBG also influences other cellular processes apart from
      mitochondrial ATP synthesis, resulting in additional inhibition of cell
      proliferation.

PMID- 7576975
TI  - Release mechanisms of [125I]meta-iodobenzylguanidine in neuroblastoma cells:
      evidence of a carrier-mediated efflux.
AB  - [131I]metaiodobenzylguanidine ([131I]MIBG) is selectively taken up and stored by
      tumours derived from the neural crest, and is used for diagnosis and treatment of
      neuroblastoma (NB). The antitumoral effect of [131I]MIBG is closely related to
      the intracellular level of the radiopharmaceutical compound, which is dependent
      on uptake and storage/release mechanisms. While MIBG uptake is well
      characterised, storage and release mechanisms are still controversial. In order
      to better characterise [125I]MIBG release mechanisms, we studied the basal and
      stimulated efflux of [125I]MIBG in the human NB cell line, SH-SY5Y, preloaded
      with 0.1 microM [125I]MIBG for 1 h. We found that [125I]MIBG basal efflux is
      highly temperature-dependent, that [125I]MIBG release, induced by cell
      depolarisation with high potassium, is mainly calcium-independent, and induced by
      exchange with cold MIBG or noradrenaline, inversion of the sodium gradient across
      the cell membrane by veratridine by substitution of sodium chloride with
      equimolar concentration of lithium chloride. The exposure of NB cells to
      imipramine, an Uptake-1 inhibitor, also produces a net stimulatory effect on
      [125I]MIBG release. However, when used in association with other releasing
      stimuli, such as higher levels of intracellular sodium or external agonists,
      imipramine abolishes the consequent increase of [125I]MIBG release. Our findings
      suggest that stimulated [125I]MIBG release is mediated by a carrier, most
      probably the uptake carrier working in a reverse mode, while a minimal fraction
      of [125I]MIBG is released by an exocytotic mechanism.

PMID- 7576976
TI  - Clinical experience with radiation enhancement by hyperbaric oxygen in children
      with recurrent neuroblastoma stage IV.
AB  - The high risk group of patients with neuroblastoma are children over 1 year with
      stage IV disease. Most series report a maximum of 20% survival at 5 years. For
      recurrent neuroblastoma stage IV, cure rates are not reported in the literature,
      but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a
      therapeutic dilemma. The outcome of radiation therapy is variable. A very
      important factor in tumour treatment remains tumour hypoxia, and others, such as
      metabolic factors, also play a role. Combined application of radiation modifiers
      may influence the final survival rate. In an attempt to improve the survival of
      recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta
      Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may
      not be used as a determinant of the usefulness of a treatment for stage IV
      neuroblastoma disease, a better one is not available. In this study, at 28
      months, a cumulative probability of survival of 32% was recorded for patients
      treated with [131I]MIBG and hyperbaric oxygen compared to 12% for [131I]MIBG
      treatment alone. These preliminary results are promising but further studies are
      needed to reveal substantial therapeutic gain.

PMID- 7576977
TI  - First line targeted radiotherapy, a new concept in the treatment of advanced
      stage neuroblastoma.
AB  - 33 previously untreated advanced stage neuroblastoma patients were treated with
      [131I]meta-iodobenzylguanidine (MIBG). The number of treatments varied between 2
      and 7 per patient (mean 3). Toxicity was seldom severe. Only thrombocytopenia WHO
      grade 4 was noticed. Response was documented before surgery for the primary
      tumour was performed. There was one complete response (CR), 18 partial responses
      (PR), 11 had stable disease (SD) and 3 had progressive disease (PD). After MIBG
      therapy and surgery, 12 of 33 patients achieved a CR. This approach is feasible,
      comparable to multidrug chemotherapy in efficacy and less toxic. Long term
      results are not known yet.

PMID- 7576978
TI  - Meta-iodobenzylguanidine uptake in platelets, megakaryoblastic leukaemia cell
      lines MKPL-1 and CHRF-28-11 and erythroleukaemic cell line HEL.
AB  - The major toxicity encountered with [131I]-Meta-iodobenzylguanidine (MIBG)
      therapy in neuroblastoma patients is an often isolated thrombocytopenia. We
      believe that this results from MIBG-induced radiotoxicity of the megakaryocytes.
      Since it is difficult to obtain enough human megakaryocytes for uptake studies,
      we investigated whether the megakaryocytic cell lines, MKPL-1, CHRF-288-11 and
      HEL, are good models to study serotonin and MIBG accumulation in human
      megakaryocytes. Compared with platelets, low levels of specific MIBG accumulation
      (imipramine-sensitive) were shown in all cell lines, but that of serotonin was
      negligible in MKPL-1 and CHRF-288-11. Furthermore, the proportion of specific
      uptake of both MIBG and serotonin appeared greatest in the HEL cells. Although
      these cells seem to be good candidates to study serotonin and MIBG uptake, they
      are not a good model to investigate MIBG and serotonin accumulation in human
      megakaryocytes since they have no functional storage granules.

PMID- 7576979
TI  - A new approach in the treatment of stage IV neuroblastoma using a combination of
      [131I]meta-iodobenzylguanidine (MIBG) and cisplatin.
AB  - The outlook for disseminated neuroblastoma (NB) continues to be dismal. NB is a
      radiosensitive tumour. Owing to its high concentration in NB lesions, [131I]meta
      iodobenzylguanidine [131I]MIBG has the potential for specifically delivering very
      large radiation doses to the malignant cells. Encouraging results have been
      reported with [131I]MIBG used alone in patients resistant to conventional therapy
      and at diagnosis. We report the first attempt to explore the integration of this
      new treatment modality with chemotherapy. Among the drugs effective in NB,
      cisplatin was chosen because of its high degree of activity against NB, its mild
      haematological toxicity and the known synergism between cisplatin and radiation.
      4 patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and 1
      with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were
      investigated with combined therapy (CO-TH). Two complete remissions and one
      partial remission were observed in these patients 4-6 weeks following only a
      single course of both cisplatin and [131I]MIBG at "standard" dosage. The only
      toxicity was haematological, which was significant and relatively long-lasting,
      but was not associated with any serious infections or bleeding tendency. The
      general condition of these patients during the entire study period was excellent.
      The fourth patient, investigated at diagnosis with a modified less intensive
      treatment, obtained a partial remission with mild haematological toxicity. During
      the subsequent courses of intensive multidrug chemotherapy, this patient showed
      haematological toxicity comparable with that experienced by patients treated with
      an identical drug combination, but without previous treatment with CO-TH. The
      provisional conclusion of this ongoing study is that this new form of CO-TH
      appears most effective in obtaining a rapid and excellent response in heavily
      pretreated relapsed patients with progressive disease, and should be further
      investigated in earlier stages of the disease.

PMID- 7576982
TI  - Exposure and schedule dependency of etoposide in neuroblastoma and leukaemia
      cells in vitro.
AB  - Using an in vitro clonogenic assay system, we examined the relationship between
      concentration, duration and schedule of exposure to etoposide and cytotoxicity in
      three cell lines. Two cell lines (SK-N-SH and IMR32) were derived from human
      neuroblastomas, and one (L1210) was the original murine leukaemia cell line used
      to define schedule dependency of etoposide in vivo. Cytotoxicity was found to be
      determined by the product of concentration and duration of exposure over a 120
      fold range of durations and a 100-fold range of concentrations. No difference in
      cytotoxicity was seen following equivalent exposure either continuously or in two
      separate intervals. In one cell line, exposure to etoposide when at confluence
      led to a highly resistant subpopulation comprising 10-15% of the entire cell
      number. This did not seem to be associated with any difference in the rate of
      etoposide efflux from cells preloaded with 3H-etoposide. We conclude that
      etoposide does not show schedule dependency in vitro, but cytotoxicity is related
      to total exposure to etoposide. The schedule dependency seen in vivo may possibly
      arise from host pharmacokinetic factors.

PMID- 7576981
TI  - Antiproliferative potential of cytostatic drugs on neuroblastoma cells in vitro.
AB  - The role of single drugs in the treatment of neuroblastoma is poorly defined. We,
      therefore, tested neuroblastoma cell survival after a 72 h exposure to one of 19
      cytostatic drugs by monolayer proliferation assay. 6 cell lines (IMR-5, Kelly, SK
      N-SH, GI-CA-N, CHP-100, CHP-134) were selected on the basis of MYCN amplification
      and PGY1 overexpression. ED50 drug concentrations were related to plasma levels
      achievable in patients during chemotherapy. More effective substances were
      mitoxantrone, doxorubicin, hydroxyurea, bleomycin, dactinomycin, cisplatinum,
      thiotepa, melphalan, carboplatinum, etoposide, vincristine, cytarabine, 6
      thioguanine, cyclophosphamide, ifosfamide and zilascorb. Parental drugs
      (cyclophosphamide, cisplatinum) appeared more cytotoxic on a molar basis than
      derived drugs (ifosfamide, carboplatinum). Less effective drugs included 5
      fluorouracil, 6-mercaptopurine, CCNU and procarbazine. Fractional application of
      a given dose was more efficient than a single dose of cyclophosphamide,
      ifosfamide and cisplatinum. The tested neuroblastoma cell lines showed distinct
      sensitivities to cytostatic drugs. Cell lines with MYCN amplification appeared
      more sensitive than PGY1 overexpressing cells. In conclusion, comparative in
      vitro testing of cytostatic drugs may provide a rationale for their clinical
      evaluation. Investigation of drug combinations and application of the monolayer
      proliferation assay to tumour biopsy material for preclinical chemosensitivity
      testing are clearly warranted.

PMID- 7576980
TI  - Deferoxamine followed by cyclophosphamide, etoposide, carboplatin, thiotepa,
      induction regimen in advanced neuroblastoma: preliminary results. Italian
      Neuroblastoma Cooperative Group.
AB  - Based upon phase I and II studies of deferoxamine alone and in combination with
      cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D
      CECaT), we initiated a single arm multicentre trial in 1992 for advanced
      neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following
      4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was
      moderate and mainly reversible myelosuppression. The post-surgically defined
      responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk
      patients included 24 complete responses, 26 partial responses, and 3 minor
      responses, and 4 patients had progressive disease. These patients are being
      followed to determine the impact of this programme on their overall survival.

PMID- 7576984
TI  - In vivo targeting of human neuroblastoma xenograft by anti-GD2/anti-Fc gamma RI
      (CD64) bispecific antibody.
AB  - Antidisialoganglioside (GD2) monoclonal antibodies can target in vitro and in
      vivo neuroblastoma cells. However, their in vivo use is limited by the presence
      of high levels of circulating IgG which hamper the recruitment of effector cells
      through the high affinity Fc gamma RI (CD64). A bispecific Fab' x Fab'
      antiGD2/antiFc gamma RI antibody (7A4 bis 22), which binds outside the IgG
      binding site of Fc gamma RI, was therefore developed. This antibody binds both
      human GD2+ neuroblastoma and Fc gamma RI+ activated macrophages in vitro. It can
      localise a GD2 positive neuroblastoma xenografted on Nu/Nu mice. Scintigraphy
      tumour/muscle ratios showed that targeting with this antibody has an excellent
      selectivity for the tumour over normal tissues. Furthermore, although its whole
      body clearance is more rapid than that of the 7A4 parental antibody over the
      first 48 h, its selective tumour uptake is similar, as shown by
      immunoscintigraphy imaging. Thus, such a bispecific antibody may represent an
      efficient tool for in vivo therapy of neuroblastoma through its ability to
      recruit Fc gamma RI+ effector cells even in presence of circulating IgG and to
      bind concomitantly GD2+ tumour cells.

PMID- 7576983
TI  - Cyclopentenyl cytosine and neuroblastoma SK-N-BE(2)-C cell line cells.
AB  - We studied the effect of cyclopentenyl cytosine (CPEC) on human neuroblastoma SK
      N-BE(2)-C cell line cells. CPEC had an IC50 value of 100 nM for non-synchronised
      SK-N-BE(2)-C cells. These cells were arrested in G0/G1-phase or early S-phase of
      the cell cycle upon treatment with CPEC. After treatment of synchronised S-phase
      cells with 1 microM CPEC, the number of cells present after 3 days was less than
      10% of that observed for the untreated cells. S-phase synchronised cells treated
      with CPEC and deoxycytidine showed an increased viability in comparison with
      cells treated with CPEC alone. Approximately 15% of the cells treated with CPEC
      and deoxycytidine traversed through one cell cycle. The amount of CTP declined to
      undetectable levels within 3 h after addition of 1 microM CPEC. The presence of
      cytidine prevented, to a large extent, the cytostatic effect of CPEC.

PMID- 7576985
TI  - First experience with prognostic factors in unselected neuroblastoma patients.
      The Austrian Neuroblastoma 87 Study.
AB  - Between January 1987 and December 1993, 117 patients were registered in the
      Austrian A-NB87 study. The male/female ratio was 1.18, with 50 patients below the
      age of 1 year at diagnosis. Patients were assigned to stage according to the
      result of primary surgery in localised disease. Age, ferritin and neuron specific
      enolase were used in addition in stage III disease for risk-adapted treatment.
      Adrenal or pelvic primary tumour sites were mainly associated (81%) with advanced
      disease. The median observation time of the study is 3.5 years. The overall
      survival at 3 years was excellent in low stage disease and IVs patients, i.e.
      100% for stage I and IIA (20 patients), 92% in stage IVs (13 patients), 81% in
      stage IIIA (18 patients) and 69% in stage IIB (8 patients). Stage IV (38
      patients) showed a survival rate of 51%, whereas stage IIB (10 patients) had the
      worst outcome in this study, i.e. 20%, due to treatment-related toxicity.
      Significant unfavourable prognostic factors were neuron specific enolase (NSE) >
      100 ng/ml, ferritin > 300 micrograms/ml and amplified MYCN. This study achieved a
      better survival rate in stage IV patients and a subgroup of stage III in
      comparison to our previous study (Padiatrie und Padologie 1986, 21, 269) and
      gives the basis to further reduce treatment intensity in low-risk disease based
      on biological factors. However, prognosis for high-risk cases was still poor in
      spite of a very aggressive treatment concept.

PMID- 7576986
TI  - The treatment of advanced neuroblastoma. Results of the Spanish Neuroblastoma
      Study Group (SNSG) studies.
AB  - The Spanish Neuroblastoma Study Group has conducted a study on advanced
      neuroblastoma (N-I-87), which included 33 stage III and 60 stage IV neuroblastoma
      children more than 1 year of age, enrolled between October 1987 and April 1992.
      They were staged according to Evans and treated with induction chemotherapy (IC)
      consisting of 3 courses of cyclophosphamide-doxorubicin alternating with 3 of
      high-dose cisplatin-teniposide. Evaluation after IC and surgery demonstrated an
      overall response rate of 88% for stage III and 69% for stage IV. In the latter,
      complete responses and good partial responses were 33 and 14%, respectively.
      After surgery, children received maintenance chemotherapy (all stage III except 2
      and 30 stage IV) or autologous bone marrow transplantation (ABMT) (11 stage IV),
      the distribution was not randomised. Probability of survival at 5 years was 0.60
      +/- 0.12 for stage III and 0.24 +/- 0.07 for stage IV. A significant difference
      in survival at 5 years was found between "good responders" and "non-responders"
      to initial chemotherapy.

PMID- 7576987
TI  - Risk factors for colon neoplasia--epidemiology and biology.
AB  - Epidemiological, physiological and molecular models of colon carcinogenesis have
      been proposed. Consistent epidemiological risk factors include reduced plant-food
      intake (increased risk); elevated meat intake (increased risk); higher physical
      activity (reduced risk); and increased alcohol intake (increased risk). At the
      physiological level, these lifestyle variables may trigger processes that provide
      explanations for the associations: higher meat, fat and alcohol means more
      heterocyclic amines and higher levels of bile acids; higher plant food means
      higher intake of several anticarcinogens and fibre fermentation that produces
      volatile fatty acids; exercise has a variety of beneficial effects. This
      complexity is elaborated further in the context of the colonic milieu where
      interactions among digesta, bacteria and epithelial cells occur. The long-term
      likelihood of cancer is the summation of moment-to-moment changes in the colonic
      milieu brought about by this interaction. Possible relationships between
      established epidemiological risk factors, genetic susceptibility and somatic
      genetic changes are outlined.

PMID- 7576988
TI  - Update on the differential diagnosis, surveillance and management of hereditary
      non-polyposis colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is the most common hereditary
      form of colorectal cancer (CRC), accounting for approximately 10% of the total
      CRC burden. HNPCC lacks premonitory physical stigmata, thereby making the family
      history crucial for diagnosis. Advances in molecular genetics during the past 2
      years have led to the cloning of four HNPCC genes (MHS2, MLH1, PMS1 and PMS2). It
      is now possible to provide presymptomatic DNA testing followed by genetic
      counselling for gene carriers. Some studies have shown that adenomas in HNPCC are
      larger, more villous, and have more high grade dysplasia than sporadic cases,
      suggesting an accelerated adenoma-carcinoma sequence. Given the early age of
      onset and proximal predominance of CRC, we initiate colonoscopy at age 20-25
      years and we recommend that it be performed every 1-2 years. The wealth of
      clinical and molecular genetic knowledge currently available to physicians about
      HNPCC can be used effectively for cancer control.

PMID- 7576989
TI  - Genetic epidemiology of colorectal cancer.
AB  - Genetic epidemiological methods have played an integral role in the
      characterisation of the genetic susceptibilities to colorectal cancer. Classic
      epidemiological approaches, such as case-control and prospective cohort studies,
      that utilise family history information have laid the foundation for the more
      specialised family-based genetic methods, segregation analysis and linkage
      analysis. The genetic epidemiology of colorectal cancer can be characterised by
      several themes: the consistently increased risk of colorectal cancer in first
      degree relatives of patients with colorectal cancer; genetic predisposition to
      some, if not the majority of colorectal neoplasms; and genetic heterogeneity of
      the inherited colorectal cancer syndromes. With the rapid development of
      molecular genetic techniques, new opportunities for further research include
      studies to estimate the proportion of colorectal cancer that is accounted for by
      genetic susceptibility, the number of loci that may be involved, and most
      importantly, gene-environment interaction studies, not only of the inherited
      syndromes, but of common colorectal cancer.

PMID- 7576991
TI  - DCC: linking tumour suppressor genes and altered cell surface interactions in
      cancer?
AB  - The Deleted in Colorectal Cancer (DCC) gene is a candidate tumour suppressor gene
      encoding a neural cell adhesion molecule-like transmembrane protein. Over the
      last year, data supporting DCC inactivation in multiple tumour types have
      continued to accumulate. Functional studies suggest that DCC may participate in
      signalling pathways that regulate cell proliferation and/or differentiation, two
      cellular processes that often go awry during tumorigenesis.

PMID- 7576990
TI  - p21ras: an oncoprotein functioning in growth factor-induced signal transduction.
AB  - p21ras is a small GTPase that functions as a molecular switch in intracellular
      signal transduction pathways activated by a large variety of growth factors. In
      50% of colorectal tumours, one of the genes for p21ras is mutated resulting in a
      constitutive active protein. Recently, progress has been made in the elucidation
      of the signalling pathways in which p21ras is involved. After a ligand binds to
      growth factor receptors, in particular receptor tyrosine kinases, a guanine
      nucleotide exchange factor is activated, which results in p21ras in the GTP-bound
      form. This GTP-bound form of p21ras interacts with the protein kinase raf1 and
      induces the activation of a kinase cascade, resulting in various cellular
      responses. This kinase cascade is part of an integrated network of both positive
      and negative signalling events.

PMID- 7576992
TI  - ApcMin: a mouse model for intestinal and mammary tumorigenesis.
AB  - Min (multiple intestinal neoplasia) is a mutant allele of the murine Apc
      (adenomatous polyposis coli) locus, encoding a nonsense mutation at codon 850.
      Like humans with germline mutations in APC, Min/+ mice are predisposed to
      intestinal adenoma formation. The number of adenomas is influenced by modifier
      loci carried by different inbred strains. One modifier locus, Mom-1 (modifier of
      Min-1), maps to distal chromosome 4. Intestinal tumours from both B6 (C57BL/6J)
      and hybrid Min/+ mice show extensive loss of the wild-type allele at Apc. B6
      Min/+ female mice are predisposed to spontaneous mammary tumours. The incidence
      of both intestinal and mammary tumours can be increased in an age-specific manner
      by treatment with ethylnitrosourea (ENU). Min mice provide a good animal model
      for studying the role of Apc and interacting genes in the initiation and
      progression of intestinal and mammary tumorigenesis.

PMID- 7576995
TI  - Role of short-chain fatty acids in the prevention of colorectal cancer.
AB  - Short-chain fatty acids (SCFAs: acetate, propionate, n-butyrate) arising in the
      large bowel during bacterial fermentation of dietary fibre and starch have
      paradoxical effects on colonic epithelial proliferation. While the three major
      SCFAs stimulate proliferation of normal crypt cells, n-butyrate and, to a lesser
      degree, propionate inhibit growth of colon cancer cell lines. At the molecular
      level, n-butyrate causes histone acetylation, favours differentiation, induces
      apoptosis and regulates the expression of various oncogenes. To understand the
      complex effects of SCFAs on carcinogenesis, it is important to study the
      intermediate stages of the adenoma-carcinoma sequence where a "switch" from
      stimulation to suppression of cell proliferation must occur.

PMID- 7576994
TI  - The role of nonsteroidal anti-inflammatory drugs in colorectal cancer prevention.
AB  - Colorectal cancer is the second leading cause of cancer death in the U.S.A.
      Recent research suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) are
      effective in the prevention of colorectal neoplasia. This review summarises the
      results of research in animals and humans of these compounds in preventing
      tumours of the colorectum.

PMID- 7576993
TI  - Role of bile acids in colorectal carcinogenesis.
AB  - Dietary factors are considered important environmental risk determinants for
      colorectal cancer development. Epidemiological studies have shown that a high fat
      (or meat) intake is associated positively and a high starch, fibre (non-starch
      polysaccharide), vegetable and fruit intake negatively with colorectal cancer
      incidence. One mechanism by which these effects are possibly exerted is through
      the metabolism of secondary bile acids. Secondary bile acids are formed after
      enzymatic deconjugation and dehydroxylation of primary bile acids in the large
      bowel by anaerobic bacteria. It has been shown that these compounds can have
      tumour-promoting capacities in animal experiments. In epidemiological studies,
      colonic cancer risk is related to the faecal bile acid concentration. In serum
      and bile of patients with colonic adenomas, more deoxycholic acid was detected
      than in healthy controls. Secondary bile acids are toxic to several cell systems
      at physiological concentrations. The exact mechanism by which these amphiphilic
      molecules exert their action is not well understood. It might act through
      membrane damage, intracellular mitochondrial action or genotoxic effects. So far
      the evidence that bile acids are involved in colonic carcinogenesis is largely
      circumstantial. It is, however, well accepted that environmental factors, such as
      dietary habits influence genetic susceptibility. Bile acids could play a
      promoting role in this process.

PMID- 7576996
TI  - Calcium and vitamin D: possible protective agents against colorectal cancer?
AB  - Nutritional factors are important determinants of colorectal cancer risk. Diets
      high in fat and/or low in fibre are especially recognised to increase risk.
      Dietary calcium and vitamin D have been suggested to be protective against
      colorectal cancer. With respect to calcium, its possible effect is thought to be
      mediated at least in part through intraluminal precipitation of hydrophobic,
      cytotoxic substances, in particular fatty and bile acids, which can promote
      colorectal cancer development. Data from studies in vitro and in animals support
      a protective effect of calcium, but studies in humans, both epidemiological and
      interventional, have given inconclusive results. With respect to vitamin D, data
      from only a small number of studies are available. Results suggest a protective
      effect by inhibition of cell proliferation, mediated through specific receptors.
      It is concluded that there are currently insufficient reasons to supplement
      subjects at increased colon cancer risk with calcium or vitamin D, especially
      when dietary intake of these substances is in agreement with general guidelines.

PMID- 7576997
TI  - Phenotype and cancer risk of various polyposis syndromes.
AB  - The gastrointestinal polyposis syndromes are disorders with multiple intestinal
      polyps. Three of these disorders, familial adenomatous polyposis, Peutz-Jeghers
      syndrome and juvenile polyposis are associated with increased risk of colorectal
      as well as extracolonic cancers. A description of the phenotype and associated
      cancer risk is provided for each.

PMID- 7576999
TI  - The potential roles of nm23 in cancer metastasis and cellular differentiation.
AB  - The majority of cancer patients succumb to the consequences of metastatic
      disease. A correlation of increased nm23 expression to low metastatic potential
      has been established in several malignancies, based on published prognostic
      studies with tumour cohorts and transfection studies. Transfection of highly
      metastatic MDA-MB-435 human breast carcinoma cells with nm23-H1 cDNA resulted in
      a significant reduction in the metastatic potential in vivo. These transfections
      also showed inhibition of colonisation and motility, as well as morphological and
      biosynthetic differentiation in vitro. The biochemical mechanism of Nm23-H1
      action, as well as the identity of proteins involved in its functional
      biochemical pathway, are still unknown. We summarise published and recent
      research concerning the role of the nm23 gene in metastasis and normal cellular
      differentiation.

PMID- 7577000
TI  - Significance of angiogenesis in tumour progression and metastasis.
AB  - Angiogenesis is defined as a vascular neoformation usually of capillary origin.
      This phenomenon is important during development and under several physiological
      and or pathological conditions. In recent years, progress has been made to
      understand this phenomenon at the molecular level. This includes the
      identification of potent angiogenic factors, the appreciation of the role of
      proteases, the importance of the extracellular matrix, and the emerging
      characterisation of signal transduction pathways in endothelial cells. Two
      important participants in angiogenesis are molecules from the fibroblast growth
      factor (FGF) and the transforming growth factor-beta (TGF-beta) family. In our
      laboratory, we have extensively studied the roles and mechanisms of action of the
      major FGF prototype, FGF-2 and of the TGF-beta member, TGF-beta 1. Different
      isoforms of FGF-2 have been previously described, a high molecular weight (HMW)
      form associated with the nucleus and 18 kDa bFGF that is cytoplasmic. These two
      forms of FGF-2 also exhibit different functions when expressed endogenously. TGF
      beta is formed from a latent complex by plasmin-dependent and plasmin-independent
      pathways. With the exception of macrophages, the plasmin-dependent pathway
      requires coculture conditions, urokinase, and the concentration of TGF-beta on
      the cell surface by the mannose-6-phosphate receptor and transglutaminase. Other
      important angiogenic modulators include vascular endothelial growth factor (VEGF)
      and angiostatin. The nature of the tumour angiogenesis factor is not yet known
      with certainty, but several identified and not yet identified angiogenic factors
      may act in concert. It is hoped that an angiostatic treatment for cancer will be
      derived from these molecular studies.

PMID- 7576998
TI  - Molecular mechanisms for organ-specific colon carcinoma metastasis.
AB  - The mechanistic basis of a metastatic cell's ability to proliferate in the
      parenchyma of certain organs and develop organ-specific metastases remains
      largely unknown. Signals from paracrine and/or autocrine pathways may regulate
      tumour cell proliferation, with the eventual outcome dependent on the net balance
      of stimulatory and inhibitory factors. Recent data demonstrate that organ
      microenvironments can modulate gene expression of tumour cells, including
      regulation of growth at the organ-specific metastatic site. Analyses of highly
      metastatic human colon carcinoma (hCC) cells selected in nude mice as well as in
      situ mRNA hybridisation analyses of archival colon carcinoma specimens correlated
      high levels of epidermal growth factor receptor with the malignant hCC cell's
      ability to grow in the liver parenchyma. These same metastatic cells can also
      respond to specific mitogens produced by tissue undergoing repair, demonstrating
      that physiological signals can be utilised by neoplastic cells. This article will
      address experimental evidence supporting the premise that organ-derived,
      paracrine growth factors regulate the growth of malignant cells that express the
      appropriate receptors.

PMID- 7577001
TI  - Prognostic value of plasminogen activators and their inhibitors in colorectal
      cancer.
AB  - Colorectal tumorigenesis is associated with remarkable changes in the plasminogen
      activation system at the tissue level. The sequence of normal mucosa-adenomatous
      polyp-adenocarcinoma-metastasis is accompanied by an increase in the urokinase
      type of plasminogen activator, the urokinase receptor and the inhibitors type-1
      and type-2, with a concurrent decrease in the tissue-type plasminogen activator.
      Overall survival analysis of colorectal cancer patients, with a follow-up of more
      than 5 years, revealed that several of these components, in both the carcinomas
      and their corresponding normal mucosa, are of prognostic value independent of
      major clinicopathological parameters. Therefore, the plasminogen activation
      cascade not only contributes to the invasive and metastatic growth of colorectal
      tumours, but might also have a clinical impact with respect to adjuvant and
      intervention therapy.

PMID- 7577002
TI  - CD44 in colon cancer.
AB  - Alternative splicing of ten different variant exons (v1-v10) is responsible for
      the creation of a large number of different CD44 surface proteins. Some of these
      proteins play decisive roles in the metastatic spread of rat tumours. Also in
      human cancers, CD44 splice variants are frequently expressed in advanced states
      of tumorigenesis. In breast cancer and in non-Hodgkin's lymphomas expression of
      exon v6 is correlated with poor prognosis of patient survival. In colorectal
      carcinogenesis, expression of exon v5 is an early tumour marker since it is
      already detectable on small dysplastic polyps (but not on normal colon
      epithelium). In contrast, exon v6 expression occurred with increased frequency
      with tumour progression, and its expression on colorectal tumours indicated
      reduced survival probability. Most likely, tumours carrying the CD44 v6 epitope
      acquire selective advantage during tumour progression and metastasis formation.
      This could be a proliferative advantage since mice transgenic for the CD44
      isoform CD44v4-v7 on T lymphocytes show an accelerated T-dependent immune
      response as compared with non-transgenic siblings.

PMID- 7577003
TI  - Interference with the adenoma-carcinoma sequence.
AB  - Epidemiological, pathological, and genetic studies indicate that most colorectal
      cancers arise in benign neoplastic polyps (adenomas). The likelihood of malignant
      change increases with adenoma size and volume of villous tissue. Adenomas are
      monoclonal products of a single stem cell mutation. Acquired genetic mutations
      and chromosomal deletions that occur late in the polyp-cancer sequence have been
      well described, although the initiating events leading to micro-adenoma formation
      are still unknown. Both inherited and environmental factors are implicated.
      Although the evidence in support of the adenoma-carcinoma sequence is indirect,
      it is compelling. Chemoprevention trials have not yet identified effective
      methods of primary prevention. Colonoscopic resection of adenomas (secondary
      prevention) plus post-polypectomy surveillance markedly decreases the incidence
      of colorectal cancer.

PMID- 7577004
TI  - The problem of de novo colorectal carcinoma.
AB  - From April 1985 to March 1995, colonoscopy was carried out at our institution in
      24,059 patients, 31,800 times in symptomatic and/or asymptomatic average risk
      persons. 184 submucosal invasive carcinomas were detected. Unlike protruding-type
      lesion, the depressed-type invades the submucosal layer, even though the size is
      within 10 mm. The depressed type of invasive carcinoma accounted for 20 lesions,
      and represented 10.9% (20 of 184) of all the invasive carcinomas. The pit pattern
      of depressed-type lesions shows a small round pit (type IIIs pit pattern) and
      that of carcinoma lesions shows the irregular pit and non-structure (type V pit
      pattern).

PMID- 7577005
TI  - Radiology in the detection and prevention of colorectal cancer.
AB  - Imaging techniques available for detection of colorectal cancer include barium
      enema, endoscopy, computed tomography (CT), ultrasound, magnetic resonance (MR)
      and immunoscintigraphy. Technical advances continue rapidly and prompt frequent
      re-evaluation of the optimal approach to management of these patients. Barium
      enema and colonoscopy are the main techniques for evaluation of symptomatic
      patients, although CT may well assume the predominant role within a few years.
      Variation in quality of barium enemas and colonoscopy poses a challenge for
      continuing medical education (CME) activities. Screening of asymptomatic
      individuals has to be considered separately for high, moderate and low risk
      population. Recommendations have to be made at present in the absence of evidence
      of effectiveness. Staging of disease pre-operatively is of limited value. Follow
      up after surgery should be primarily clinical although endoscopy, CT, MR,
      ultrasound and immunoscintigraphy all have specific roles in the evaluation of
      patients suspected of harbouring recurrent disease.

PMID- 7577006
TI  - Screening for clonal genetic alterations.
AB  - Clonality is a fundamental characteristic of all human cancers. One cancer cell
      gives rise to daughter cells, all of which exhibit the same change that initially
      provided a growth advantage to the parent cell. Accumulation of further genetic
      changes in subsequent daughter cells, each providing an additional growth
      advantage, has been well documented in human cancer. Correlation of these clonal
      genetic changes with histopathological progression has led to development of a
      molecular progression model for colorectal cancer. The identification of genetic
      markers able to identify the clonal outgrowth of neoplastic cells has proven
      useful in the detection of a variety of primary neoplasms.

PMID- 7577007
TI  - Pitfalls in polypectomy: from gene to cure.
AB  - Unsuspected problems are commonly encountered during colonoscopic polypectomy.
      This paper identifies the most frequent difficulties and describes solutions to
      them. One of the most important pitfalls is overlooking a lesion or tumour in the
      colon; this can only be solved by better training, experience and care, although
      it may happen in the best of hands with the most knowledgeable colonoscopist.
      Other pitfalls addressed include the stuck snare, use of a gastroscope for the
      difficult sigmoid polyp, and methods to aid discovery and retrieval of the
      polypectomy specimen.

PMID- 7577008
TI  - Polyps and polypectomy surveillance--role of the histopathologist.
AB  - The traditional roles of the pathologist are those of diagnostician, and being
      able to communicate these diagnoses back to the clinician in a clear unambiguous
      form so that subsequent therapy can be planned. Important findings may require
      more direct communication, particularly when the implications involve a choice
      between therapeutic options. Some diagnoses have implications that require an
      educational role for the pathologist; these in turn may evolve into a research
      role, based on clinico-pathological correlation, active basic science research or
      simply supplying tissue for research. Clinicians must also be aware that the same
      biopsy can be interpreted in numerous ways, depending upon the clinical
      situation.

PMID- 7577009
TI  - Follow-up after polypectomy: consensus?
AB  - Patients who have had a colorectal adenoma resected have an increased risk of
      subsequent cancer and may benefit from follow-up surveillance. Surveillance
      strategies should be tailored to the assessed risk of each individual patient. A
      number of long-term follow-up studies indicate that the risk of metachronous
      neoplasia is higher if on index colonoscopy there were multiple (> or = 2)
      adenomas, or if any adenoma was large (> or = 1 cm), contained villous tissue or
      severe dysplasia, or if the patient had a family history of colorectal neoplasia.
      Data from the U.S. National Polyp Study indicate that polyp resection and follow
      up surveillance greatly reduces the incidence of metachronous cancer, and that
      the first follow-up colonoscopy does not need to be performed for 3 years.
      Current data have been incorporated into a comprehensive consensus practice
      guideline.

PMID- 7577011
TI  - Upper intestinal surveillance in familial adenomatous polyposis.
AB  - Our understanding of the natural history of upper gastrointestinal (GI)
      involvement in familial adenomatous polyposis (FAP) is still evolving, although
      we know that the main cause of death after colectomy in FAP is upper GI
      malignancy, affecting 5% of patients. The aim of duodenal surveillance is to
      target high risk individuals and identify cancers early. We have screened 200
      patients prospectively and have observed that duodenal polyposis progresses
      slowly, but there are some young people who have severe disease who merit close
      observation. We pay particular attention to endoscopic technique and histological
      detail, and use a duodenal staging system. Patients are offered randomisation to
      studies of chemopreventive agents, and those with advanced disease are considered
      for surgery. Successful management is inhibited by our deficient knowledge of the
      natural history of upper gastrointestinal polyposis, and by our inability to
      identify high risk individuals with histological markers rather than because of
      any technological deficiencies in endoscopic equipment.

PMID- 7577010
TI  - Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in
      50 families.
AB  - A surveillance programme comprising either colonoscopy of sigmoidoscopy plus
      barium enema every 2-3 years was instituted in 50 hereditary nonpolyposis
      colorectal cancer (HNPCC) families. The families included 238 patients with
      colorectal cancer (CRC) (mean age at diagnosis: 43.7 years; range: 16-86 years).
      These patients had 597 first-degree relatives of whom 493 could be traced and 388
      (79%) accepted the invitation for screening. The control group were relatives
      (index patients) with symptomatic CRC. The average follow-up duration was 5 years
      (1-20 years). Screening led to the detection of adenomas in 33 patients and CRC
      in 11 patients. Pathological examination revealed 1 Dukes' A, 7 Dukes' B and 3
      Dukes' C cancers. In contrast, among the control group 47% had advanced CRC
      (Dukes' C or distant metastases). The 5-year survival of the screen-detected
      cases was 87% versus 63% in the control group. Of the 11 CRC cases in the
      screening group, 4 were detected within 1-4 years after a negative colonic
      examination. A large proportion of the polyps found in the screening and control
      groups showed a villous growth pattern and/or a high degree of dysplasia. We
      conclude that periodic examination of HNPCC families allows the detection of
      cancer at an earlier stage than in patients not under surveillance. Because of
      the possibly more aggressive nature of polyps associated with HNPCC, we recommend
      a screening interval of 1-2 years.

PMID- 7577012
TI  - Recurrent polyps in the ileo-anal pouch or rectum in familial adenomatous
      polyposis.
AB  - Most small bowel polyps in familial adenomatous polyposis (FAP) occur in the peri
      ampullary region, and distal small bowel adenomas and carcinomas are
      comparatively less common. As standard therapy in FAP consists of proctocolectomy
      with ileal pouch anal anastomosis, or ileorectal anastomosis, it is essential to
      be aware of the potential for adenomatous polyp formation in the terminal ileum
      and rectum. Ileal adenomas are found in 9-20% of patients with FAP, and new
      polyps may develop after colectomy. Ileal lymphoid hyperplasia and polyps are 2-4
      times more common than adenomas, may be indistinguishable from adenomas on
      examination (requiring biopsy for diagnosis), and tend to regress after
      colectomy. Adenomas may arise in pouches, usually after an interval of several
      years, and have been documented to occur in the terminal ileum up to 25 years
      after colectomy. At pouch construction, rectal mucosectomy may theoretically fail
      to remove all mucosa at risk. Small islets of rectal mucosa may remain after this
      technically difficult operation, and the late development of cancer, up to 20
      years postoperation has been noted. A stapled anastomosis may arguably have a
      better physiological result, but a greater amount of residual rectal mucosa may
      increase late cancer risk. Annual endoscopic follow-up of pouches is recommended.
      All polyps or suspicious lesions should be biopsied, excised or destroyed,
      preserving a sample for histology. After ileorectal anastomosis, cancer risk in
      the rectal stump increases with chronological age, with risk ranging from 5-10%
      at age 50 years, to 14-29% at age 60 years. Surveillance of the rectal stump in
      FAP is recommended every 4-6 months. There may be a role for prostaglandin
      synthesis inhibitors in some patients.

PMID- 7577014
TI  - Grading of dysplasia.
AB  - Lethal carcinomas are still found inadvertently in patients under surveillance;
      some may not be preceded by conventional dysplasia. However, there is a survival
      advantage for cancers detected endoscopically rather than symptomatically, and,
      therefore, by preventing them by colectomy when dysplasia first becomes apparent.
      It may, therefore, be unnecessary to grade dysplasia when found, for if
      unequivocally present, then immediate consideration of colectomy is appropriate.
      It is unreasonable to expect colonoscopists to rebiopsy what might be a minute
      patch of dysplasia that has no distinguishing features endoscopically. Aneuploidy
      deserves consideration as a potential marker of patients at particular risk of
      developing dysplasia, who might undergo more frequent colonoscopy and biopsies
      than those without the presence of aneuploidy. There is still considerable
      interobserver variability in the grading of dysplasia by pathologists; part of
      this may be because grading occurs around a mean, the width of the tails of this
      distribution curve determining interobserver variation.

PMID- 7577013
TI  - Photodynamic therapy for polyps in familial adenomatous polyposis--a pilot study.
AB  - Photodynamic therapy (PDT) produces localised necrosis with light after prior
      administration of a photosensitising drug. As PDT lesions in the gastrointestinal
      tract heal so well, the technique is suitable for repeated endoscopic use. In
      this study, PDT was used to treat large polyps (four duodenal and two colorectal)
      unsuitable for surgery in 6 patients with familial adenomatous polyposis (FAP).
      Patients were sensitised with 60 mg/kg 5-aminolaevulinic acid (ALA) orally or
      intravenous (i.v.) 2.0 mg/kg Photofrin. Laser treatment was performed 6 h after
      ALA or 48 h after Photofrin using a gold vapour laser. Necrosis was only
      superficial (up to 1.8 mm) using ALA but much deeper using Photofrin. The one
      malignant polyp (8 mm diameter in the colon) showed a complete response using
      Photofrin. All healed safely with no complications. Photofrin worked better, but
      caused cutaneous photosensitivity lasting up to 3 months. ALA cleared within 2
      days, but its use is limited by the superficial effect. Better results with ALA
      may be obtained using higher drug doses or modified light dosimetry. Fluorescence
      microscopy showed no evidence of selectivity of photosensitisation between
      neoplastic and normal tissue. PDT is a promising treatment for inoperable polyps
      in patients with FAP, but further work is required to optimise the treatment
      conditions.

PMID- 7577015
TI  - Molecular genetics of dysplasia in ulcerative colitis.
AB  - Numerous molecular genetic events occurring in the development of sporadic
      colorectal neoplasia have been previously defined. The most frequent genetic
      alterations are mutations of the APC, KRAS, and TP53 genes, as well as loss of
      the DCC gene and of the second TP53 allele. The data from several groups indicate
      that these genes play an important role in ulcerative colitis-associated
      dysplasias and cancer, as they do in sporadic colorectal adenomas and carcinomas.
      KRAS and TP53 mutations were detected in dysplasia, but also in villous
      regeneration and active colitis, and affect a subpopulation of the cells
      composing these lesions. We conclude that in histologically defined dysplasia,
      clones can be found that genetically represent precancerous lesions in ulcerative
      colitis. Seen in this way, part of the active colitis and villous regeneration
      lesions might be considered as preneoplastic. When present, KRAS mutation is an
      excellent genetic marker to map populations of preneoplastic cells.

PMID- 7577017
TI  - Is colonoscopic cancer surveillance in ulcerative colitis essential for every
      patient?
AB  - Surveillance aims to diagnose precancer or cancer at a surgically curable stage.
      Cancer complicating ulcerative colitis affects only 1-2 per million of the
      general population annually. The risk is low within 10 years of disease onset,
      and in proctitis or left-sided colitis. It is approximately one in 120 per year
      for those with extensive disease after 10 years from onset. Results of
      surveillance programmes from regional hospitals among 423 patients led to surgery
      for precancer or cancer once every 123 colonoscopies; there were no cancer deaths
      during surveillance and all 4 cancers were Dukes' stage A or B. At referral
      centres, many patients have dysplasia at the first colonoscopy. Two-thirds of
      cancers in colitis develop in the recto-sigmoid; flexible sigmoidoscopy has a
      role in surveillance which is untested. Colonoscopic surveillance is not
      appropriate for most patients with colitis; it is worthwhile but not essential
      for those with long-standing extensive disease.

PMID- 7577018
TI  - Colonic cancer surveillance in ulcerative colitis is not essential for every
      patient.
AB  - It is generally recognised that there is an increased risk of colonic cancer in
      patients with long-standing extensive colitis, and regular annual or biennial
      colonoscopic surveillance protocols have been recommended in order to detect
      early cancer. There is, however, little evidence to suggest that these protocols
      are of value. There have been no properly conducted controlled trials in this
      area, and the studies that have been reported are flawed by selection bias, the
      inclusion of patients with "pseudo disease" and protocol violators. Many studies
      have not distinguished between "screening colonoscopy" and "colonoscopic
      surveillance". Some have not drawn attention to the failures in the surveillance,
      i.e. patients with Dukes' grade C or worse, and overall the conclusions drawn
      have been unrealistically optimistic. The diagnosis of low grade dysplasia which
      has been accorded importance is insensitive, non-specific and is subject to gross
      interobserver error. It is of little clinical value. Colonoscopic surveillance
      using currently available techniques is of only marginal benefit to patients
      included within the protocol. It is not cost-effective and cannot be made to be
      so.

PMID- 7577016
TI  - Endoscopic appearance of dysplasia and cancer in inflammatory bowel disease.
AB  - Dysplastic alteration of mucosa may occur in flat or raised mucosal lesions. Over
      95% of dysplastic foci occur in flat mucosa. Flat dysplasia is occasionally
      visible macroscopically as areas of discolouration, velvety-villous appearance,
      or peculiar fine nodular thickening. The prevalence of macroscopically visible
      flat dysplasia is unknown. Raised dysplasia or DALM (dysplasia associated lesion
      or mass) occurs in less than 5% of patients with dysplasia. DALMs are polypoid
      structures of firm consistency, discoloured mucosa and irregular nodularity.
      DALMs cannot be distinguished endoscopically from early malignancy. The presence
      of DALMs has an ominous significance.

PMID- 7577019
TI  - Rectal cancer: the surgical options.
AB  - The hypothesis is considered that the tissue block relevant to optimal cure
      encompasses the integral visceral mesentery of the hind gut, or mesorectum.
      Surgical technique can recreate the tissue planes around an intact globular
      specimen which must not be torn or the margin compromised. This emphasis on the
      "perfect tumour package" has reduced the local recurrence rates in a consecutive
      personal series of 333 rectal cancer operations to 4% in those operated upon for
      cure. If patients with metastases or residual disease at presentation are
      included, the figure increases to 7%. Introduction of selective pre-operative
      high dose radiotherapy (DXT) for locally unfavourable cancers has combined with
      further attention to surgical detail to achieve a 5-year follow-up period
      (January 1990-January 1995) without a single case of locally recurrent disease.
      Problems remain with healing of the ultra-low anastomosis.

PMID- 7577020
TI  - Current chemotherapeutic possibilities in the treatment of colorectal cancer.
AB  - To date, the best treatment modality for colorectal cancer is a surgical excision
      of the primary tumour. Adjuvant therapy can be added to the surgical treatment
      and can consist of adjuvant chemo-, immuno- or radiotherapy. In the U.S.A.,
      adjuvant chemotherapy with 5-fluorouracil (5FU) and levamisole is advocated as
      standard treatment for patients with localised poor risk (Dukes stage C) colon
      cancer. Not every clinician is convinced of the usefulness of adjuvant
      chemotherapy. Therefore, confirmatory clinical trials are still ongoing to
      compare no adjuvant treatment with 5FU/levamisole adjuvant treatment. Treatment
      with 5FU/leucovorin has been shown to be effective as adjuvant therapy. In rectal
      cancer, radiotherapy can be added to the primary surgical treatment. It is still
      unproven whether radiotherapy should be given pre-, peri, or postoperatively, and
      whether chemotherapy should be added to this multimodality regimen. If
      chemotherapy is applied as a radio-sensitiser, a continuous infusion is
      preferable to daily bolus injection. Much effort has been put into the
      improvement of the response rate of 10-15% 5FU, used as a single agent in the
      treatment of advanced colorectal cancer. Biochemical modulation of 5FU with
      leucovorin and interferon, different schedules of 5FU administration and hepatic
      arterial therapy have all been attempted. Higher response rates have been
      reported with these treatment modalities, unfortunately without improvement of
      survival, except for the intra-arterial approach. Recently, two new drugs have
      shown efficacy in the treatment of advanced colorectal cancer. A phase II trial
      with Tomudex (ZD1694), a new antifolate thymidiylate synthase inhibitor, produced
      a response rate of 25% in patients with advanced colorectal cancer.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577021
TI  - Chemo- and dietary prevention of colorectal cancer.
AB  - Because of the substantial morbidity and mortality associated with colorectal
      cancer, and the limitations and costs of treating this disease, prevention
      remains a desirable (if elusive) goal. In this paper, we discuss both chemo- and
      dietary prevention strategies for colorectal cancer, recognising the overlap and
      cross-fertilisation between these two approaches. Chemopreventive compounds are
      drugs and are developed for clinical use like other pharmaceuticals. A formal
      sequential multi-phase programme for development of chemopreventive agents has
      been instituted by the National Cancer Institute, U.S.A. This involves both
      preclinical efficacy and clinical studies. Such studies increasingly employ
      preneoplastic intermediate markers (such as proliferation measures) as well as
      neoplastic adenomas as endpoints. Promising chemopreventive agents include
      calcium, aspirin and other non-steroidal anti-inflammatory drugs, vitamins (such
      as vitamin E and folate), 2-dimethylfluorornithine (DFMO), oltipraz and
      ursodeoxycholic acid. Several lines of evidence implicate diet in colorectal
      carcinogenesis. Key hypotheses in diet and colorectal cancer (which are amenable
      to prevention, research and action), in addition to those pertaining to the
      micronutrient chemopreventives, include dietary fat and fibre, food mutagens, red
      meat, and overall low-fat, high-fibre, high fruit and vegetable dietary patterns
      and cuisines. Several adenomatous polyp recurrence studies with fibre supplement,
      macronutrient or dietary pattern interventions have been undertaken
      internationally. We review early findings from this new generation of studies,
      and anticipate the future results from these investigations and the ambitious
      Women's Health initiative in the U.S.A. Results from these studies may convert
      the promise of colorectal cancer prevention into reality.

PMID- 7577022
TI  - The use of prognostic markers in surgery for colorectal cancer.
AB  - The basis for prognostic prediction after surgery for colorectal cancer remains
      the various pathological staging systems based on that of Dukes. Serum prognostic
      markers have not shown significant independent prognostic power compared with
      these predictive tools. Much energy has been expended in examining the ability of
      serum markers to predict recurrent tumour prior to the onset of symptoms.
      Carcinoembryonic antigen (CEA) has been a particular subject of attention, and
      has been widely, though variably, advocated as a useful predictor in these
      circumstances. It has been estimated that around half a million Americans are
      presently undergoing regular postoperative CEA monitoring to this end.
      Controversy continues regarding the therapeutic utility of such monitoring. This
      may be resolved when the results of the only randomised trial in the field are
      published in the near future. No other serum marker, nor any combination of
      markers, has been shown clearly to be superior to CEA as a predictor of recurrent
      tumour.

PMID- 7577023
TI  - Intra-operative ultrasound in detection of liver metastases.
AB  - Intra-operative ultrasonography (IOUS) combined with palpation of the liver is
      significantly more accurate than either computer tomography (CT) or percutaneous
      ultrasonography employed pre-operatively. Accurate staging of colorectal cancer
      is essential for appropriate treatment strategy. There is a large impact of IOUS
      on tumour staging and treatment especially in patients with suspected liver
      lesions at pre-operative imaging.

PMID- 7577024
TI  - Planning of liver surgery using three dimensional imaging techniques.
AB  - In the simplified Couinaud classification, in which the liver is divided into
      eight segments, each supplied by a central vasculo-biliary sheath, little
      attention is given to the high prevalence of anatomical variations which occur,
      especially in the right hemiliver. Using volumetric acquisition techniques, such
      as magnetic resonance imaging or spiral computed tomography scanning, detailed
      insight into the individual segmental anatomy can now be obtained in a non
      invasive manner. The significance of this anatomical insight lies in the planning
      of anatomical resections, whereby the relationship between tumour and individual
      segmental anatomy can be depicted in a three-dimensional format. As such, three
      dimensional (3D) liver imaging helps to design an individualised resection,
      tailored to the topographical relationship between individual segmental anatomy
      and tumour tissue present. Three dimensional liver imaging is of most practical
      value if a resection of one or more segments or sectors is considered, especially
      in the right hemiliver. In these cases, 3D liver imaging can demonstrate the
      precise location of the scissuras to the surgeon pre-operatively.

PMID- 7577026
TI  - Detection of recurrence after surgery for colorectal cancer.
AB  - Of all patients operated for colorectal cancer, 1 in 3 will suffer from cancer
      recurrence, and most of these patients will die from disseminated disease.
      Postoperative follow-up aims at improving these grim figures. This sound idea has
      not been supported by any empirical data. In the current article, we discuss some
      theoretical issues concerning colorectal cancer follow-up, and present results of
      a cost-effectiveness analysis, used to model the natural history of colorectal
      cancer recurrence and the costs and effects of follow-up and re-operation. The
      expected results of three policies were calculated: no follow-up, selective
      follow-up and intensive follow-up. For most patients, follow-up will only lead to
      a significant increase in costs, without increase in (quality-adjusted) life
      expectancy. Colorectal cancer follow-up is not "evidence-based medicine".

PMID- 7577025
TI  - Prognostic value of pathological characteristics of colorectal cancer.
AB  - The overall cure rate of colon cancer has not improved dramatically in the last
      decade, remaining at approximately 60% 5-year survival. The main reason for this
      lack of progress is that at the moment the primary tumour is resected, a
      significant proportion of the patients with seemingly localised disease already
      has (undetectable) micrometastases, mostly in the liver. The most important
      prognostic indicators have been extension of the tumour into the bowel wall and
      the presence of lymph node metastasis, as expressed in the Dukes classification.
      However, in the Dukes B and C categories, these parameters are poor predictors of
      final outcome. For improvement of the prognosis, in addition to earlier
      detection, more aggressive (adjuvant) treatment of high risk patients would be a
      rational strategy. This requires development of new therapeutic modalities, but
      also reliable stratification of patients according to high risk or low risk for
      recurrent disease. In recent years, many attempts have been made to improve the
      prediction of final outcome. Parameters studied include inflammatory response to
      the primary tumour, tumour cell growth fraction, tumour cell differentiation,
      genetic abnormalities and expression of genes involved in invasion and
      metastasis. Although some of these newer parameters have significant predictive
      value, in multivariant analyses, most appear to have limited independent value.
      Recent studies indicate that genetic abnormalities might be important new
      prognostic indicators. One of the most promising findings in this area is an
      allelic loss of chromosome 18q, which allows division of Dukes B patients into
      subgroups with low risk and high risk for recurrent disease.

PMID- 7577028
TI  - Nerve-sparing surgery with lateral node dissection for advanced lower rectal
      cancer.
AB  - 133 patients who underwent nerve-sparing surgery with lateral dissection for
      lower rectal cancer were analysed for survival and functional results, operative
      burdens, and modes of recurrence. In 84% of patients an acceptable urinary
      function was preserved. Operative time averaged 334 min, and blood loss averaged
      935 ml. The 5-year survival rate was 67% in all patients, and 88% for Dukes' A,
      74% for Dukes' B and 59% for Dukes' C. According to the number of positive nodes,
      the 5-year survival rate comprised 83% of patients with up to three nodes, and
      34% of those with more than four nodes. Local recurrent rates were 2.7% in
      patients with Dukes' B and 13% with Dukes' C. At present, pelvic nerve-sparing
      procedures with lateral dissection is the most promising surgery, guaranteeing
      both adequate lymphadenectomy and preservation of urinary function.

PMID- 7577027
TI  - The effect of blood transfusions on survival after surgery for colorectal cancer.
AB  - The immunosuppressive effect of allogeneic blood transfusions can be associated
      with a poor prognosis for cancer patients. Predeposit autologous blood
      transfusions could be a solution to overcome this putative deleterious effect. We
      performed a randomised clinical study to compare the effects of autologous with
      allogeneic blood transfusions in colorectal cancer patients. There was no
      significant difference in disease-free survival between both randomisation arms.
      However, the transfused patients had a significantly shorter disease-free
      interval as compared with the non-transfused patients. This association of
      transfusions with recurrent disease was only the case for local recurrences,
      whereas the incidence of distant metastases was unaffected. We conclude that the
      use of a predeposit autologous blood transfusion programme does not improve the
      prognosis in colorectal cancer patients. The negative association between blood
      transfusions and cancer recurrence is only true for local recurrences, which
      suggests that not the blood transfusions themselves but rather the circumstances
      necessitating them are the real predictors of prognosis.

PMID- 7577029
TI  - Local surgical treatment of rectal cancer.
AB  - Local surgical treatment of rectal cancer as a curative procedure is only
      indicated in early rectal cancers. Our indication is T1 low risk cancer according
      to Hermanek. Conventional transanal procedures are limited to tumours located in
      the lower rectum and the precision of the excision is restricted by the
      limitation of the surgeon's visualisation during the procedure. Dorsal approaches
      show a high rate of complications and should no longer be performed. Transanal
      endoscopic microsurgery is a technique which has been in clinical use since 1983.
      By the use of complex technology, precise surgical dissection under a magnified
      stereoscopic view is possible. With the use of up to three instruments and new
      instrument technologies, full thickness excision up to segmental resection is
      possible. The resulting defect is routinely closed at the end of the procedure by
      a continuous endoscopic suture. The latest results based on 265 tumour resections
      at the University of Tubingen and 1900 operations based on a German review show
      positive results. The recurrence rate as a sign of precision of procedure is low
      and the postoperative complication rate is lower than with conventional
      procedures.

PMID- 7577030
TI  - Treatment of colorectal cancer metastases confined to the liver.
AB  - Hepatic metastases are a major cause of death in patients with disseminated
      colorectal cancer. The prognosis of patients with hepatic metastases is very poor
      and mainly determined by the extent of hepatic disease at presentation. In these
      patients, the goal of any treatment is to obtain a complete tumour remission in
      the liver; this is the only way to obtain a significant survival benefit. In this
      overview, we summarise data from (i) studies comparing survival of patients after
      primary resection of liver metastases with survival after repeat liver
      resections, (ii) studies comparing hepatic arterial infusion of fluoropyrimidines
      with systemic delivery of these anticancer drugs, and (iii) phase I/II studies on
      isolated liver perfusion (ILP) with alkylating compounds. Furthermore, we discuss
      alternative strategies to combat liver metastases, including those taking
      advantage of an ILP setting.

PMID- 7577032
TI  - Double dynamic graciloplasty and coloperineal pull-through after abdominoperineal
      resection.
AB  - In patients with a very low rectal carcinoma, an abdominoperineal resection with
      the creation of a permanent colostomy is the surgical treatment of choice.
      Creation of a colostomy can be avoided without compromise to oncological safety.
      The distal colon is pulled through to the perineum and both gracilis muscles are
      used to create a new sphincter and pelvic floor. These muscles are electrically
      stimulated by an implanted neurostimulator. Contraction is then no longer
      dependent upon volition and, due to fibre transformation, the muscle will become
      fatigue-resistant. The outcome in 11 patients was assessed. After a mean follow
      up of 1.3 years, continence was achieved in 7 patients, and 2 patients are
      awaiting completion of the therapy. In 2 patients, necrosis of the distal colon
      led to failure of the technique. There was no local recurrence, but 2 patients
      had distant metastasis. Double dynamic graciloplasty after abdominoperineal
      resection proves to be an oncologically safe procedure with a reasonable chance
      of continence and a life without a stoma in the majority of patients.

PMID- 7577031
TI  - Radio-immunotargeting in colorectal carcinoma.
AB  - Colorectal cancer is one of the most frequently studied diseases for
      investigating cancer detection using radiolabelled monoclonal antibodies. From
      many clinical studies it has become clear that with radio-immunotargeting (RIT)
      it is possible to visualise approximately 70% of known sites of colorectal cancer
      and to find otherwise occult tumour deposits in approximately 10% of patients.
      The intra-operative use of a gamma detection probe increases the detection rate
      of clinical occult intra-abdominal tumour sites to 30-40%. However, this clinical
      experience has also disclosed the many difficulties and pitfalls connected with
      this technique, with respect to antibody-, tumour-, patient- and isotope-related
      factors. Upstaging or early disclosure of disseminated disease by RIT has not
      proven to be beneficial in terms of improved survival, but might be of use in the
      management of an individual patient. The laborious and costly RIT technique,
      difficult scan interpretation and the lack of proven survival benefit precludes
      its routine use in clinical practice. However, the promising results warrant
      further study to improve the technique, and to validate the clinical usefulness
      of radio-immunotargeting.

PMID- 7577033
TI  - An overview of adjuvant therapy for colorectal cancer.
AB  - Adjuvant therapy of colorectal cancer is one of the most active areas of clinical
      oncology research. Although the data for the benefits from early trials of
      adjuvant therapy were inconclusive, these trials suffered from inadequate sample
      sizes, poor staging, potentially suboptimal treatment regimens and ill-defined
      prognostic subgroups. More recently, larger trials of higher scientific quality
      have demonstrated that regimens of fluorouracil plus levamisole in stage III
      colon cancer and fluorouracil with postoperative radiation in stages II and III
      rectal cancer can reduce mortality. Such regimens have now become standard
      practice in settings in which treatment is believed to be both efficacious and
      tolerable, and when the overall impact of therapy is considered to be clinically
      relevant. More recent advances in adjuvant treatment of colorectal cancer further
      support the role of fluorouracil-based regimens. Peri-operative portal vein
      infusions of fluorouracil demonstrate improved relapse-free and overall survival,
      and infusional fluorouracil administered with radiation for rectal primaries
      appears superior to less intensive bolus fluorouracil regimens. Completed trials
      of fluorouracil plus leucovorin combinations are awaiting maturation, with
      expectations for superior adjuvant activity based on demonstrated improved
      response rates for biochemically modulated fluorouracil in advanced metastatic
      colorectal cancer. New systemic agents are also entering large-scale adjuvant
      trials, including monoclonal antibody 17-1a, given alone and in conjunction with
      standard fluorouracil regimens. Additional cytotoxic drugs, including CPT-11 and
      Tomudex, offer new opportunities for alternative adjuvant regimens for the large,
      heterogeneous population of patients with resected colorectal cancer.

PMID- 7577034
TI  - Chronomodulation of chemotherapy against metastatic colorectal cancer.
      International Organization for Cancer Chronotherapy.
AB  - Toxic effects of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), two active drugs
      against metastatic colorectal cancer, varied by 50% or more according to
      circadian dosing time in mice or rats. Adaptation of chemotherapy delivery to
      circadian rhythms (chronotherapy) was assessed in fully ambulatory outpatients,
      using multichannel programmable pumps. These devices allowed us to reliably test
      the clinical relevance of such a chronotherapy principle. First, single agent 5
      day chronomodulated schedules were devised and assessed in Phase I and II trials
      with 5-fluorouracil (5-FU, peak delivery at 4:00 h) or oxaliplatin (L-OHP, peak
      at 16:00 h). Both schedules were then combined, folinic acid (FA) being added,
      synchronous with 5-FU infusion. This three-drug chronomodulated regimen (chrono
      FFL) produced a 58% response rate (95% C.I.: 48-68%) in 93 patients with
      metastatic colorectal cancer, 46 of whom had previously received chemotherapy. In
      the first European randomised trial in 92 previously untreated patients,
      chronomodulated three-drug delivery achieved 53% response, as compared to 32% in
      those patients receiving flat infusion (P = 0.038). These respective figures were
      confirmed in a subsequent multicentre randomised trial involving 186 additional
      patients. Since the most active schedule was also the least toxic one by 2- to 10
      fold, chrono-FFL was further intensified in three consecutive Phase II trials
      involving a total of 200 additional patients. Results suggest that both response
      rate and quality were further improved with such treatment intensification. Thus,
      chrono-FFL more than doubled the activity of chemotherapy against metastatic
      colorectal cancer in a multicentre European setting.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577035
TI  - Regional chemotherapy of colorectal cancer.
AB  - Hepatic metastases are a major cause of mortality in patients with colorectal
      carcinoma. The rationale for hepatic arterial chemotherapy has an anatomical and
      pharmacological basis as presented below. The randomised studies are reviewed and
      demonstrate a significantly higher response rate with hepatic arterial therapy
      versus systemic therapy. Survival information is difficult to evaluate because
      some of the studies are small, and some had a crossover design, but two studies
      demonstrate a significant improvement in 2-year survival after hepatic arterial
      therapy compared with systemic therapy. New combinations of 5-fluoro-2
      deoxyuridine with dexamethasone and/or leucovorin have produced response rates as
      high as 72%, median survivals of 22-27 months, and a 2-year survival of 66%. More
      recent studies on patients who have failed previous systemic chemotherapy have
      produced response rates around 50%. Hepatic toxicity, especially biliary
      sclerosis, is the dose limiting toxicity, occurring in 6-25% of patients. To
      truly define the role of regional therapy, a more accurate randomised study will
      have to be conducted, to determine if hepatic arterial infusion improves the
      quality of life and, or survival in patients with hepatic metastases from
      colorectal cancer.

PMID- 7577036
TI  - ZD1694 (Tomudex): a new thymidylate synthase inhibitor with activity in
      colorectal cancer.
AB  - ZD1694 (Tomudex) is a new antifolate which is a specific inhibitor of thymidylate
      synthase (TS). Evidence suggests that ZD1694 has a spectrum of activity that only
      partially overlaps with 5-fluorouracil (modulated with leucovorin) against colon
      tumours in vitro. Potent cytotoxic activity is dependent upon active uptake into
      cells via the reduced folate/methotrexate cell membrane carrier (RFC) and
      subsequent metabolism to polyglutamated forms (tri, tetra and pentaglutamates).
      These polyglutamates are approximately 60-fold more active as TS inhibitors and
      are not effluxed readily from cells. Extensive polyglutamation also occurs in
      various mouse tissues (e.g. small intestinal epithelium, liver and kidney),
      resulting in high tissue/plasma drug ratios which persist for a prolonged period.
      ZD1694 has antitumour activity in mice, although the high plasma thymidine in
      this species complicates: (1) the interpretation of therapeutic index; (2) tumour
      types in which activity is likely to be observed; and (3) translation of doses
      and schedules for clinical evaluation. ZD1694 entered clinical study and has
      completed Phase I and II evaluation, with activity observed in several tumour
      types. Appreciable activity in the Phase II colorectal study (29% objective
      response rate on interim analysis) led to the current Phase III study, randomised
      against 5-fluorouracil/leucovorin.

PMID- 7577037
TI  - CPT-11 (irinotecan) in the treatment of colorectal cancer.
AB  - Colorectal cancer is one of the most common cancers in the Western World.
      Although 50% of patients are cured by surgery alone, the outcome is poor in high
      risk patients (Dukes stages B2 and C) despite adjuvant chemotherapy with 5
      fluorouracil (5-FU)-based regimens. CPT-11 (irinotecan) is a promising new agent
      for the treatment of colorectal cancer with a unique mechanism of action. CPT-11
      is a DNA topoisomerase I inhibitor, which has not demonstrated susceptibility to
      the P-glycoprotein-mediated multidrug-resistant phenotype. Phase II studies with
      CPT-11 have demonstrated definite activity against colorectal cancer in both
      chemotherapy-naive and pretreated patients (response rates of 15-32% observed)
      even with clinical evidence of resistance to 5-FU. The response rate appears to
      be consistent, reproducible and equivalent to that achieved with 5-FU plus
      folinic acid in chemotherapy-naive patients.

PMID- 7577038
TI  - MDR1/P-glycoprotein expression in colorectal cancer.
AB  - Drug resistance to multiple chemotherapeutic agents is considered a major cause
      of chemotherapy failure. An extensively studied and relatively well understood
      type of cellular drug resistance is P-glycoprotein (Pgp)-mediated multidrug
      resistance (MDR). Pgp acts as an energy-dependent drug efflux pump, thereby
      decreasing the intracellular drug concentration and causing drug resistance, in
      in vitro experiments. Colorectal cancer and colorectal mucosa generally express
      high levels of Pgp, and this may contribute to the general unresponsiveness of
      colorectal cancer to natural product, anticancer drugs. The controversies
      concerning the prognostic role of Pgp expression and its contribution to tumour
      aggressiveness, and possible reasons for the disappointing results of clinical
      MDR reversal trials in colorectal cancer are discussed.

PMID- 7577039
TI  - Multidrug resistance and the role of P-glycoprotein knockout mice.
AB  - Drug resistance, be it intrinsic or acquired, is a major problem in cancer
      chemotherapy. In vitro, one well characterised form of resistance against many
      different cytotoxic drugs is caused by the MDR1 P-glycoprotein, a large plasma
      membrane protein that protects the cell by actively pumping substrate drugs out.
      Available evidence suggests that this protein may cause drug resistance in at
      least some clinical tumours. Drugs inhibiting the MDR1 P-glycoprotein activity
      are, therefore, co-administered during chemotherapy of these tumours. To predict
      the biological and pharmacological effects of the blocking of this protein, we
      have generated mice with a genetic disruption of the drug-transporting mdr1a P
      glycoprotein. These mice are overall healthy, but they accumulate much higher
      levels of substrate drugs in the brain, and have markedly slower elimination of
      these drugs from the circulation. For some drugs, this leads to dramatically
      increased toxicity, indicating that P-glycoprotein inhibitors should be used with
      caution in patients.

PMID- 7577040
TI  - Thymidylate synthase and drug resistance.
AB  - Thymidylate synthase is an important target for both fluorinated pyrimidines and
      for new folate analogues. Resistance to 5-fluorouracil (5FU) can be related to
      insufficient inhibition of thymidylate synthase. The 5FU-nucleotide FdUMP induces
      inhibition of thymidylate synthase which is enhanced and retained for longer in
      the presence of increased folate pools, for which leucovorin is a precursor. In a
      murine model system, 5FU treatment caused a 4-fold induction of thymidylate
      synthase levels which may have contributed to resistance. Addition of leucovorin
      to this treatment prevented this induction and increased the antitumour effect 2
      3-fold. In the clinical setting, 5FU administration to patients resulted in
      approximately 50% inhibition of TS after 48 h. The combination with leucovorin
      resulted in a more pronounced inhibition after 48 h (approximately 70%). A
      significant relationship was observed with outcome of treatment; when thymidylate
      synthase levels were high and inhibition was low, no response was observed. A
      separate study showed that low thymidylate synthase levels appeared to be an
      independent prognostic factor for adjuvant therapy.

PMID- 7577042
TI  - Role of leucovorin dosing and administration schedule.
AB  - Leucovorin (LV) is commonly administered in association with 5-fluorouracil (5
      FU) to enhance its cytotoxic effects. In this paper, the cellular and clinical
      pharmacology of 5-FU potentiation by LV are reviewed, and the dosing and
      administration schedules are discussed in relation to reported clinical trials.
      In vitro experimental data suggest that prolonged cellular exposures to
      relatively low LV concentrations simultaneously with prolonged 5-FU
      administration are the optimal conditions to enhance 5-FU efficacy. Clinical
      studies of 5-FU/LV in metastatic colorectal carcinoma have established that 5-day
      bolus 5-FU with low-dose bolus LV injections yield therapeutic benefits
      equivalent to those obtained with intravenous bolus schedules using higher doses
      of LV. It remains to be determined, however, if bolus administration schedules
      are the optimal clinical treatment regimens. Infusional 5-FU/LV regimens appear
      to be a strategy worthy of further clinical investigation.

PMID- 7577041
TI  - Quantitation of intratumoral thymidylate synthase expression predicts for
      resistance to protracted infusion of 5-fluorouracil and weekly leucovorin in
      disseminated colorectal cancers: preliminary report from an ongoing trial.
AB  - A clinical trial for patients with measurable, disseminated colorectal cancer is
      being conducted to determine: (1) if intratumoral expression of thymidylate
      synthase (TS) affects response to protracted-infusion 5-fluorouracil (5FU); and
      (2) whether intratumoral expression of TS increases when clinical resistance is
      found after response to 5-FU. Polymerase chain reaction technology is employed to
      determine TS expression. Using beta-actin as an internal standard, TS expressions
      for 26 patients range from 0.5 x 10(-3) to 22.6 x 10(-3). Currently, 22 patients
      are evaluable for response and TS quantitation of their measurable tumour. 8
      patients (36%) have had partial responses; 3 responding patients had been
      previously treated with 5-FU. A strong statistical association between TS
      expression and resistance to therapy has been found (P = 0.004). No patient with
      TS expression of 4.0 x 10(-3) or greater has responded. On average, patients
      previously treated with 5-FU have slightly higher levels of TS expression in
      their measurable tumours (P = 0.4). Whether responding patients will develop
      increased expressions of TS upon clinical progression of their cancer remains to
      be determined. Confirmation of these results in a larger cohort could lead to a
      scientific rationale for deciding upon specific therapy for patients with
      disseminated colorectal cancers.

PMID- 7577043
TI  - The role of interferon-alpha as a modulator of fluorouracil and leucovorin.
AB  - Several preclinical studies have demonstrated that interferon-alpha (IFN-alpha)
      may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive
      manner in a variety of human cancer cell lines. The underlying mechanism(s) have
      varied in different cancer cell lines, and include increased fluorouracil
      anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate
      synthase, stimulation of thymidine and uridine phosphorylase activities, greater
      DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets.
      These preclinical studies stimulated clinical evaluation of IFN-alpha in
      combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the
      initial clinical results appeared promising. We summarise preclinical research
      concerning the interaction of 5-FU and IFN-alpha. The rationale for combining 5
      FU with IFN-alpha and LV is discussed, and we describe our clinical experience
      with the combination of 5-FU, LV and IFN-alpha-2a. The insights and unresolved
      questions concerning the clinical application of this combination are also
      discussed.

PMID- 7577044
TI  - The role of biological response modifiers in the management of patients with
      colorectal cancer.
AB  - Biological response modifiers are agents which exert their antitumour effects
      indirectly via modulation of the host's response to the tumour. Immunotherapeutic
      approaches which fall into this category can be divided into specific and non
      specific. An example of the latter is the combination of 5-fluorouracil (5-FU)
      with levamisole which improves survival of patients with colorectal carcinoma
      when utilised in an adjuvant setting. Specific immunotherapy using active
      specific immunisation is attracting much attention. This is in part due to
      improvements in survival seen in one randomised clinical trial in an adjuvant
      setting, and also to exciting advances in the fields of tumour immunity and
      vaccine development. The development of more effective vaccines promises much for
      patients with early colorectal carcinomas.

PMID- 7577045
TI  - Prevention of manifest metastasis with monoclonal antibodies: a novel approach to
      immunotherapy of solid tumours.
AB  - Until now, surgery, chemotherapy and radiotherapy have remained the mainstay of
      current cancer therapy. The major limitation of chemo- and radiotherapy is their
      narrow therapeutic index between cancer and normal cells. In the search for less
      toxic and more specific therapies, various modalities of immunotherapy have been
      tried. It is now increasingly recognised that patients presenting with minimal
      cancer burden or micrometastatic disease will experience the greatest benefit
      from treatment with monoclonal antibodies (mAbs). The first proof of efficacy of
      a monoclonal antibody in minimal residual disease has recently been published,
      with mAb 17-1A in patients with colorectal cancer stage III after complete
      resection of the primary tumour. After a median follow-up of 5 years, antibody
      therapy reduced the overall death rate by 30% and decreased the recurrence rate
      by 27%. This result is similar to the benefit obtained in (radio)chemotherapy
      trials, however, with notably lesser toxicity. It is clear from past experience
      that all currently available treatment modalities for cancer are far from
      perfect. However, because the mechanism of action or target cells of different
      treatment modalities may be complementary in the control of tumour growth, the
      next logical step is to rationally design clinical trials that combine
      conventional chemo-, hormonal or radiation therapy with immuno- or biotherapy.

PMID- 7577046
TI  - The current role of radiotherapy in colorectal cancer.
AB  - During the last two decades, radiotherapy has become an integral part of the
      multidisciplinary approach in the treatment of patients with colorectal cancer.
      Currently, radiotherapy is seen mainly as an adjuvant therapy, sometimes in
      combination with chemotherapy, in a pre- or postoperative setting. Adjuvant
      radiotherapy alone leads to a significant reduction of local recurrence rates,
      but an impact on survival is seen only in subset analyses. Combined modality
      treatment can reduce local recurrence rates even further, and can also reduce the
      rate of distant relapses and increase survival. The acute toxicity of combined
      modality is considerably higher. Local radiation can also be use as a component
      of organ conserving local treatment for selected early lesions. Radiotherapy has
      been an important palliative treatment modality, diminishing symptoms in cases of
      inoperable primary rectal cancers or pelvic recurrences. The timing of radiation,
      surgery and chemotherapy has been under evaluation for years. For patients with
      locally advanced primary or recurrent malignancies (unresectable due to
      fixation), the preferred sequence is pre-operative irradiation with or without
      chemotherapy, followed by surgical resection. For mobile resectable lesions,
      sequencing issues are being tested in phase III randomised trials.

PMID- 7577047
TI  - Conservative and curative management of rectal adenocarcinomas by local
      radiotherapy alone.
AB  - Two hundred patients with well-differentiated adenocarcinomas of the rectum
      stages T1, T2 (113 T1, 87 T2) were accrued in two French institutions (Lyon-Sud
      and Dijon). Treatment consisted of intracavitary 50 kV X-rays (90-120 Gy in 3-4
      fractions and 4-6 weeks). A 20-30 Gy interstitial brachytherapy boost was given
      after 2-3 fractions when a limited infiltration of the rectal wall was present.
      Local failure occurred in 4.4% of T1, 19.5% of T2; nodal failure in 0.9% of T1,
      9.2% of T2. Ultimate local control after salvage of failures is 94.5%. A
      functional sphincter was preserved in 95% of patients with local control.

PMID- 7577048
TI  - Conservative treatment of rectal cancer with local excision and postoperative
      radiation therapy.
AB  - The conventional surgical treatment for patients with potentially curable
      transmural and/or node positive rectal cancer is a low anterior resection or
      abdominoperineal resection. Recently, there has been increasing interest in the
      use of local excision and postoperative radiation therapy as primary therapy for
      selected rectal cancers. The limited data suggest that the approach of local
      excision and postoperative radiation therapy should be limited to patients with
      either T1 tumours with adverse pathological factors or T2 tumours. Transmural
      tumours, which have a 24% local failure rate, are treated more effectively with
      standard surgery and pre- or postoperative therapy. The results of local excision
      and postoperative radiation therapy are encouraging, but more experience is
      needed to determine if this approach ultimately has similar local control and
      survival rates as standard surgery.

PMID- 7577049
TI  - The value of adjuvant radio(chemo)therapy for rectal cancer.
AB  - Radiotherapy has been used extensively as an adjuvant treatment with surgery for
      patients with rectal cancer. Present knowledge indicates that preoperative
      radiotherapy is more dose-efficient than postoperative radiotherapy in reducing
      local recurrence rate. Provided the dose is sufficiently high, the reduction
      exceeds 50% in all Dukes' stages and after both abdominal perineal excision and
      anterior resection. The effect on survival has not yet been proven but there are
      indications that survival may be slightly improved using preoperative
      radiotherapy, although the magnitude of this improvement is probably less than
      with postoperative chemotherapy. Of concern with all adjuvant treatments are the
      potential side-effects, and it appears that postoperative radiotherapy has more
      side-effects than preoperative radiotherapy, even if the reduction of local
      recurrences is less and proper radiation techniques are utilised.

PMID- 7577050
TI  - Radiotherapy and hyperthermia.
AB  - 72 patients with either unresectable or pelvic recurrence of colorectal cancer
      were treated with combined radiotherapy and locoregional hyperthermia. Radiation
      doses were 50 Gy or more in patients not previously treated with radiotherapy,
      and 32 Gy (8 x 4 Gy) in patients who had previously received radiotherapy.
      Hyperthermia was administered within 30 min of irradiation, and the aim was to
      give four to six sessions once or twice a week, intending to reach temperatures
      of at least 41 degrees C over 30 min. The mean of all the minimum (TMIN), maximum
      (TMAX) and median (TMED) intratumoral temperatures were 39.6, 41.1 and 40.2
      degrees C, respectively. Toxicity during hyperthermia treatment consisted mainly
      of local pain within the heated field (33%) and general discomfort (17%). In 17%
      of the patients, the hyperthermic treatment was prematurely stopped. Palliation
      was achieved in 75% of patients with a mean duration of 12 months. The percentage
      of palliated patients was higher when higher radiation doses were administered.
      No correlation between palliative effect and thermal parameters was found. A
      computed tomography scan proved objective remission was obtained in 11 patients
      (15%). Median survival was 11 months, and 17% of the patients were alive at 3
      years. The literature on combined radiotherapy and hyperthermia in colorectal
      cancer is reviewed. From this review and our own data, it is concluded that
      thermoradiotherapy is feasible. Acute and late toxicity are not major problems,
      although pain and general discomfort hamper hyperthermic treatment. The most
      disappointing fact is that, with the available hyperthermia equipment, the
      increase in intratumoral temperature does not reach, in general, the therapeutic
      range.

PMID- 7577051
TI  - A pilot study of a new therapeutic approach in the treatment of locally advanced
      stages of rectal cancer: neoadjuvant radiation, chemotherapy and regional
      hyperthermia.
AB  - The synergistic effects of hyperthermia (temperatures > or = 41 degrees C) when
      combined with radiotherapy or cytotoxic drugs, as well as a modulation of tumour
      related immunological phenomena have been demonstrated preclinically. Local or
      regional hyperthermia in combination with radiation or chemotherapy has been
      studied in patients during recent years, and has convincingly demonstrated that
      hyperthermia is feasible and tolerated by patients. Furthermore, there is strong
      evidence that hyperthermia may provide an improvement in local control as
      compared with radiotherapy or chemotherapy alone. Systems based on radiowave
      irradiation allow sufficiently tolerable and effective regional hyperthermic
      therapy in patients with rectal carcinomas. Used as part of curative pre
      operative and postoperative multimodal therapeutic strategies in high-risk
      patients with locally advanced rectal carcinomas, hyperthermia may result in
      improved local control and a higher rate of sphincter-sparing procedures. 20
      patients with non-resectable, locally advanced primary or recurring rectal
      carcinoma T3/4 entered a phase I/II study of pre-operative
      radiochemothermotherapy with folinic acid and 5-fluorouracil, radiation (45 Gy
      HD), as well as regional hyperthermia once a week followed by chemotherapy after
      surgery. The regimen proved to be sufficiently tolerable. Acute grade III or IV
      toxicities did not occur after hyperthermia. Tumour resections were performed on
      14 of the 20 patients, with 13 being complete. In 9 of the carcinomas,
      downstaging compared with the pretherapeutic stage was achieved. In 3 of 6
      patients with persistent non-resectable tumours, local control has now been
      maintained for more than 12 months. One patient progressed locally during
      neoadjuvant combination therapy. These results prompted the initiation of a
      prospective randomised study to evaluate the relative importance of regional
      hyperthermia in this setting.

PMID- 7577052
TI  - The prevention of radiation-induced small bowel complications.
AB  - Moderate dose pelvic radiotherapy is associated with a 5% severe complication
      risk related to the small bowel. Strictures and/or fistulation can occur many
      years after treatment. These complications are difficult to treat, and surgical
      treatment (excision, bypass) bears a significant morbidity risk. The risk of
      chronic diarrhoea or malabsorption may increase to 40%, depending on the
      irradiated small bowel volume. Late small bowel complications are generally
      irreversible due to vascular aetiology. Prevention of these complications can be
      achieved by limiting the volume of small bowel treated. Consequences for
      radiotherapeutic techniques in treatment for rectal cancer are multiple beam set
      up, customised blocking based on visualisation of the small bowel in the
      treatment position, and the use of a special open table-top device that results
      in a small bowel shift from the treatment field.

PMID- 7577053
TI  - Colorectal cancer: future population screening for early colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most frequent cancers in Western countries.
      The identification of individuals at risk and the early diagnosis of CRC are of
      critical importance since a large proportion can be prevented or cured by
      surgical removal before metastasis has occurred. With increasing understanding of
      the genetic basis of hereditary and sporadic (non-hereditary) CRC, it becomes
      feasible to detect genetic alterations by molecular techniques. Familial
      adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC),
      as well as early stages of spontaneous CRC, can be diagnosed by molecular
      characterisation of the adenomatous polyposis coli (APC) gene, the RAS oncogene
      and other genes in DNA from peripheral blood, stool or intestinal biopsies. With
      a better understanding of the genetic events leading to malignant transformation,
      molecular population screening should allow us to identify individuals at risk as
      well as patients with an early and potentially curable CRC. At present, careful
      patient and family history, physical examination and testing for occult blood as
      well as colonoscopy are still the key elements for clinical patient management.
      Molecular diagnosis will hopefully soon complement these analyses and should
      result in a reduction of morbidity and mortality from CRC.

PMID- 7577055
TI  - Developments in colorectal cancer surgery.
AB  - The developments in colorectal cancer since the 19th century are reviewed. Local
      recurrence of colorectal cancer after curative surgery is a major problem and may
      occur because of inadequate removal of the primary tumour and lymph node
      metastases, or intra-operative spill of tumour cells. Colorectal surgeons differ
      with regard to postoperative mortality. The best surgical technique has not yet
      been determined; there have been only two prospective randomised trials on
      surgical technique. However, it is predicted that laparoscopic surgery will have
      an important place in colorectal surgery.

PMID- 7577054
TI  - The chemotherapy of colon cancer.
AB  - Despite extensive clinical trials, mortality from colon cancer has remained
      essentially unchanged since the 1950s. However, the increasing numbers of
      complete and partial responses seen in clinical trials suggest that colon cancer
      can be successfully treated by chemotherapy, but only if the antitumour
      selectivity can be increased by a substantial amount. This will be possible by
      the introduction of new drugs with more precise mechanisms of action, such as
      those acting specifically on signalling or cell cycle control pathways shown to
      be aberrant in colon cancer. Alternatively, the selectivity of present day agents
      may be increased considerably by the selective activation of prodrugs in tumours
      (ADEPT) or by targeting them to tumours using polymers. Other new approaches
      using vaccines or some form of gene therapy will potentiate present chemotherapy,
      while the introduction of positron emission tomography (PET) scanning will allow
      the rapid detection of agents with activity that would have been missed by
      conventional measurements of response.

PMID- 7577056
TI  - Improvement of the curative management of rectal cancers by better use of
      radiotherapy.

PMID- 7577057
TI  - The protocol for a European double-blind trial of aspirin and resistant starch in
      familial adenomatous polyposis: the CAPP study. Concerted Action Polyposis
      Prevention.

PMID- 7577058
TI  - Economics in cancer care.

PMID- 7577059
TI  - Is Hodgkin's disease infectious?

PMID- 7577060
TI  - Possible effect of histamine-2 receptor blockade on the antitumour response to
      interleukin-2.

PMID- 7577061
TI  - Combined seminoma/non-seminoma should be considered as intermediate grade germ
      cell cancer (GCC).

PMID- 7577062
TI  - European School of Oncology Advisory report to the European Commission for the
      "Europe Against Cancer Programme" European Code Against Cancer.
AB  - A European School of Oncology Advisory Group has reviewed the European Code
      Against Cancer after its initial use over a 6-year period. With minor
      modifications, the original ten recommendations were found to be adequate,
      although it was agreed that an Annex was necessary to explain the scientific
      evidence supporting each point, and is presented herewith. Tobacco smoking
      clearly remains the most important cause of cancer, and now it can be quantified
      better than ever before. It is also clear that it is never too late to stop
      smoking: stopping even in middle age, prior to the onset of serious illness has a
      beneficial effect on life expectancy. Alcohol drinking is an important cause of
      cancer, and yet modest consumption levels protect against cardiovascular disease
      mortality. The optimal strategy seems to be a consumption not exceeding 2-3
      drinks per day, although this limit may be lower for women. Increased consumption
      of fruits and vegetables, reduction in consumption of fatty foods, reduction of
      obesity and increased physical activity can all be recommended to reduce cancer
      risk. Exposure to excessive sunlight remains a problem which should be limited.
      Control of occupational cancer is a three-way partnership: legislation identifies
      and limits exposure to known carcinogens, employers enact the legislation and
      workers should respect the measures introduced. There are a number of signs and
      symptoms which may lead to cancer being diagnosed earlier, and patients with
      these should be referred to a doctor. For women, participation in organised
      programmes of cervical cancer and breast cancer (after 50 years of age) should
      lead to a reduction in mortality from these forms of cancer. The key element is
      organised programmes, where quality control and quality assurance are in force.
      These revised recommendations are the result of an agreement following advice,
      review and dialogue with cancer experts throughout Europe. They were approved by
      the European Community Cancer Experts at their meeting in Bonn on 28-29 November
      1994. Their implementation by the European population should greatly reduce
      cancer incidence and mortality.

PMID- 7577063
TI  - The economics of reimbursement and technological change in cancer care.

PMID- 7577064
TI  - European School of Oncology Advisory report to the Commission of the European
      Communities for the "Europe Against Cancer Programme" cost-effectiveness in
      cancer care.

PMID- 7577065
TI  - Ten-year results comparing mastectomy to excision and radiation therapy for
      ductal carcinoma in situ of the breast.
AB  - The 10-year results of 300 patients with ductal carcinoma in situ (DCIS) without
      microinvasion are reported; 167 treated with mastectomy and 133 treated with
      excision and radiation therapy. There was a significant difference in disease
      free survival at 10 years, in favour of those treated with mastectomy, 98% versus
      81% (P = 0.0004). Multivariate analysis confirmed nuclear grade as the only
      significant predictor of local recurrence (P = 0.02) or invasive local recurrence
      (P = 0.03) in patients with DCIS treated with excision and radiation therapy.
      There was no difference in breast cancer-specific survival or overall survival
      between the two treatment groups.

PMID- 7577066
TI  - Locally advanced non-metastatic breast cancer: analysis of prognostic factors in
      125 patients homogeneously treated with a combined modality approach.
AB  - 125 stage III breast cancer patients, including 51 cases of inflammatory
      carcinoma, were treated with the following combined modality approach: three
      courses of primary 5-fluorouracil, doxorubicin, cyclophosphamide (FAC)
      chemotherapy followed by locoregional treatment and subsequent adjuvant
      chemotherapy consisting of three courses of FAC alternating with three courses of
      cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Clinical response to
      primary FAC was 65% (complete 10%). Residual tumour mass in the mastectomy
      specimen was > 1 and < or = 1 cm in 82 and 18% of cases, respectively. Complete
      pathological response following primary chemotherapy was achieved in only 3.5% of
      cases. After primary FAC and local treatment, 97% of patients were disease-free.
      Overall survival (S) and progression-free survival (PFS) at 5 years were 56 and
      34%, respectively. Univariate analysis showed that age, receptor status and
      clinical and pathological response to primary chemotherapy did not appear to
      influence treatment outcome significantly, whereas stage, presence of
      inflammatory disease and number of involved nodes had a significant impact on
      both S and PFS.

PMID- 7577067
TI  - Early alternating chemotherapy and radiotherapy schedule in limited disease stage
      small cell lung cancer.
AB  - 44 patients with limited small cell lung cancer were treated with six cycles of
      chemotherapy (cisplatinum 60 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, etoposide
      100 mg/m2 days 1-3) alternating with three courses of mediastinal irradiation,
      the first one starting 7 days after the first day of chemotherapy. A total dose
      of 55 Gy was delivered. Prophylactic cranial irradiation (30 Gy after the third
      cycle of chemotherapy) was left to the physician's discretion. 4 patients had
      radical surgery before combined modality treatment. 29 patients finished the
      scheduled program. The complete response rate (bronchoscopically confirmed) was
      25.6% after two cycles of chemotherapy and 41% at the end of treatment. Median
      survival time was 17.2 months, with an estimated survival of 32% at 2 years. Main
      toxicity was haematological with one early toxic death and six premature
      interruptions of treatment. We conclude that this treatment modality is feasible
      and efficacious. Prospective studies comparing chemotherapy with alternating or
      concurrent early radiotherapy schedules in limited disease small cell lung cancer
      are needed to determine the best treatment modality.

PMID- 7577068
TI  - Serum YKL-40: a new potential marker of prognosis and location of metastases of
      patients with recurrent breast cancer.
AB  - YKL-40 is a recently discovered glycoprotein which is related in amino acid
      sequence to the chitinase protein family, but has no chitinase activity. Although
      the function of YKL-40 is presently unknown, the pattern of its expression by
      some tissues suggests that YKL-40 could function in tissue remodelling. The
      diagnostic features and relation to survival of serum YKL-40 have not been
      examined previously in human malignancies. In the present study YKL-40 was
      measured in serum obtained from 60 patients at the time that breast cancer
      recurrence was suspected. The median serum YKL-40 in patients with visceral or
      bone metastases was 328 and 157 micrograms/l, respectively and significantly
      higher compared to controls (99 micrograms/l, P < 0.001). Kaplan-Meier survival
      curves demonstrated that survival rates after 18 months were 24% for patients
      with high serum YKL-40 (> 207 micrograms/l = the 95 percentile of controls) and
      60% for patients with normal serum YKL-40. The significance of the difference
      between the shorter survival of patients with high serum YKL-40 and the longer
      survival of patients with normal serum YKL-40 was high (P < 0.0009). When
      evaluated with other prognostic factors of survival after recurrence of breast
      cancer, serum YKL-40 and serum lactate dehydrogenase (LDH) were the most
      significant independent factors. The results indicate that determination of serum
      YKL-40 can be used as a prognostic marker related to the extent of disease and
      survival of patients with recurrence of breast cancer. In addition, the serum YKL
      40 level may be of value in the follow-up of patients with breast cancer and in
      evaluating potential metastatic spread.

PMID- 7577069
TI  - Expression of insulin-like growth factor I (IGF-I) in female breast cancer as
      related to established prognostic factors and long-term prognosis.
AB  - The expression of insulin-like growth factor I (IGF-I) was analysed
      immunohistochemically in a series of 211 breast cancers with special emphasis on
      its relationship to conventional prognostic factors and long-term prognosis.
      Altogether, IGF-I was expressed by the tumour cells in 91% of the breast
      carcinomas, and by stromal cells in 29%. The expression of IGF-I in cancer cells
      was weakly related to a high proportion of intraductal growth (P = 0.032),
      distinct tumour margins (P = 0.048) and high S-phase fraction (P = 0.074). In a
      univariate analysis, IGF-I expression in cancer cells was significantly related
      to a high survival probability in the entire cohort (P = 0.0144) as well as in
      the axillary lymph node positive tumours (P = 0.0286). Alternatively, expression
      of IGF-I in the stromal cells was related to metastasis at the time of diagnosis
      (P = 0.05), tumour diameter (P = 0.04), DNA ploidy (P = 0.07) and nuclear
      pleomorphism (P = 0.025), but it was without prognostic significance in a
      univariate analysis (P > 0.1). In a multivariate analysis, the conventional
      prognostic factors were superior to IGF-I expression in predicting the disease
      outcome, albeit expression of IGF-I in tumour stroma showed some independent
      prognostic significance in axillary lymph node negative tumours. The results
      suggest that IGF-I expression is related to malignant histopathological features
      in breast cancer, and expression of IGF-I has independent prognostic significance
      in the early phases of the disease.

PMID- 7577070
TI  - Significance of cathepsin-D expression in uterine tumours.
AB  - Cathepsin-D (Cath-D) expression was evaluated by an immunoradiometric assay in 67
      primary endometrial carcinomas and 70 cervical cancers. In the endometrial
      tumours, an inverse correlation was observed between Cath-D levels and stage (P =
      0.027) and myometrial invasion (P = 0.046). A significant correlation between
      Cath-D levels and hormone receptor status was demonstrated (P < 0.05). In
      cervical cancer, no differences in the distribution of Cath-D levels according to
      clinicopathological parameters and hormone receptors were observed. However,
      patients not responding to neoadjuvant chemotherapy had significantly lower Cath
      D values than those showing complete or partial response (P = 0.011). As far as
      prognostic significance is concerned, it appears that Cath-D expression might
      have a different role in the two uterine neoplasias. While our preliminary data
      in endometrial cancer suggest that high Cath-D levels may be a favourable
      prognostic indicator, cervical cancer patients with Cath-D+ tumours had a shorter
      disease-free survival than those with Cath-D- tumors (P = 0.017).

PMID- 7577071
TI  - Insulin-like growth factor (IGF) and IGF binding proteins in growth hormone
      dysregulation and abnormal glucose tolerance in small cell lung cancer patients.
AB  - Growth hormone (GH) regulation, glucose tolerance and serum concentrations of
      insulin-like growth factor (IGF) and IGF binding proteins (IGFBP) have been
      investigated in small cell lung cancer (SCLC) patients. Elevated serum GH was
      observed in the patient and smoking control groups but not in non-smoking control
      subjects. Glucose suppression of GH was observed in the few SCLC patients with
      raised basal GH but most SCLC patients exhibited a paradoxical increase in GH
      following oral glucose. Abnormal glucose tolerance and insulin resistance with
      respect to plasma glucose was observed in most patients. Patients showing GH
      dysregulation exhibited higher serum concentrations of IGFBP-2 than those showing
      no increase in GH. Abnormal glucose tolerance was associated with decreased serum
      concentrations of IGF-I. Given reports of elevated IGFBP secretion in SCLC and
      inhibition of IGF-I bioactivity by IGFBPs, these findings may indicate that
      increased serum IGFBPs disrupt IGF-I regulation of GH secretion and glucose
      homeostasis.

PMID- 7577073
TI  - Intermittent continuous infusion of 5-fluorouracil and low dose oral leucovorin
      in patients with gastrointestinal cancer: relationship between plasma
      concentrations and clinical parameters.
AB  - Modulation of 5-fluorouracil (5-FU) by leucovorin and continuous infusion of 5-FU
      can both result in enhanced therapeutic efficacy. The main objective of this
      study was to determine the maximum tolerated dose (MTD) of oral leucovorin in
      combination with continuous infusion of 5-FU for 14 days every 4 weeks at a dose
      of 300 mg/m2/day in 30 patients with gastrointestinal cancer. The MTD of oral
      leucovorin was established at 10 mg/day. Dose-limiting toxicities were mucositis,
      diarrhoea and hand-foot syndrome. Plasma leucovorin concentrations were below the
      detection limit of the assay (< 0.5 microM). Plasma 5-FU concentrations varied
      considerably from 0.06 to 11.3 microM. A relation between toxicity, response and
      plasma concentration of 5-FU could not be established. Our data may indicate that
      even very low plasma concentrations of leucovorin are able to modulate 5-FU. In
      17 patients with colorectal cancer the response rate was 24% (95% CI: 7-50%),
      which is comparable to other treatment schedules with leucovorin or to continuous
      infusion of 5-FU alone.

PMID- 7577072
TI  - Nausea and vomiting in fractionated radiotherapy: a prospective on-demand trial
      of tropisetron rescue for non-responders to metoclopramide.
AB  - A prospective trial was performed to better assess the risk of nausea and
      vomiting and the rescue value of tropisetron (TRO), a 5-HT3 receptor antagonist,
      in 88 patients undergoing fractionated radiotherapy to the abdomen or to large
      supradiaphragmatic fields and failing a first anti-emetic trial with
      metoclopramide (MET). Nausea was graded 0 (absent), 1 (mild), 2 (moderate) and 3
      (severe). Nausea requiring anti-emetics (> or = grade 2) was present in 64% of
      the patients. MET was able to control nausea (< or = grade 1) in 26 of 58
      patients (45%) who developed > or = grade 2 nausea during radiation treatment (2
      patients vomiting without nausea included). 34 patients required TRO, and 31
      experienced immediate relief. However, nausea (> or = grade 2) recurred in 7
      patients from 1 to 3 weeks after starting TRO. Sex, age, field type and field
      size (cm2) did not influence the incidence and severity of nausea and vomiting.
      Only 24/88 patients vomited after starting radiotherapy. MET helped to eliminate
      emesis in one third of these patients. TRO helped to control vomiting in 73% of
      the salvaged patients. Constipation was observed in 8 patients on TRO and was a
      reason to stop the medication in 4 cases.

PMID- 7577074
TI  - The Tygerberg Hospital Children's Tumour Registry 1983-1993.
AB  - This study records the disease profile and outcome of all 492 children with
      confirmed cancer below the age of 15 who were admitted to Tygerberg Hospital,
      South Africa, from 1983 to 1993. The black (48.3%), so-called coloured (30.3%)
      and caucasian (21.3%) children did not represent a confined geographical area.
      Leukaemia (22.8%), brain tumours (20.5%), lymphomas (15.2%), nephroblastomas
      (10%), neuroblastomas (8.5%) and retinoblastomas (5.7%) were the most common
      tumours. All children were treated with standard protocols and included in the
      Kaplan-Meier survival analyses. 14 patients were lost to follow-up. Projected
      survival in (acute lymphoblastic leukaemia) ALL was 63% in white children, but
      only 17% in black children. Survival was 65% in stage 1 and 2 Wilms' tumour, and
      exceeded 50% in medulloblastoma and astrocytoma. So-called African Burkitt's
      lymphoma occurred in all population groups. Overall, 5-year survival in Hodgkin's
      disease was 70%. Black and coloured children with neuroblastoma presented mainly
      with stage 3 and 4 disease. All 26 black and coloured children with
      retinoblastoma had a negative family history and advanced disease which needed
      enucleation.

PMID- 7577075
TI  - Haemopoietic growth factors and childhood cancer.

PMID- 7577076
TI  - Case clustering, Epstein-Barr virus Reed-Sternberg cell status and herpes virus
      serology in Hodgkin's disease: results of a case-control study.
AB  - The Leukaemia Research Fund Data Collection Study (DCS) is a specialist registry
      of leukaemias and lymphomas. The present study involves 494 cases of Hodgkin's
      disease (HD) registered with the DCS between 1985 and 1989. This entire data set
      has been tested for localised spatial clustering using an established nearest
      neighbour method with 18% of all cases in young people classified as clustered (P
      < 0.05). No clustering was found in older cases. Subsamples were selected from
      the registered cases for a pilot study in which case clustering, herpes virus
      antibody titres and Epstein-Barr virus (EBV) presence within the Reed-Sternberg
      (RS) cells (EBV-RS status) were investigated together. Firstly, a case-control
      study of HD in young people or nodular sclerosing (NS) subtype (39 HD cases and
      26 healthy controls) found significant elevation of antibody titres to EBV-viral
      capsid antigen (VCA), EBV-early antigen (EA) and human herpes virus 6 (HHV-6) in
      HD cases compared with controls. EBV viral genome was present in 5 cases and 4 of
      these were in clusters of HD in young people. Elevation of antibody titres to the
      EBV antigens was not associated with case clustering or EBV-RS status. Antibody
      titres to HHV-6 differed significantly between EBV-RS+ and EBV-RS- cases (P =
      0.04). Geometric mean titres for HHV-6 for EBV-RS+ and EBV-RS- cases were 11.5
      and 73.7, respectively, with the former lower than the control value of 20.5.
      Secondly, a cluster study included all other cases (n = 14) in clusters
      containing known EBV-RS+ cases. 3 further cases were EBV-RS+ positive but no
      cluster consisted entirely of positive cases. Overall, 5/16 clustered, 2/12
      peripheral and 1/25 random cases in these studies were EBV-RS+ (P = 0.017). The
      interpretation of these results in terms of shared aetiological exposures of
      cases within clusters and the roles of EBV and HHV-6 is discussed, and hypotheses
      for testing in future studies proposed.

PMID- 7577077
TI  - Changes in the incidence and mortality of testicular cancer in Scotland with
      particular reference to the outcome of older patients treated for non
      seminomatous germ cell tumours.
AB  - This paper describes the temporal pattern of germ cell testicular cancer in
      Scotland between 1960 and 1990. The effect of age on the prognosis of patients
      with non-seminomatous germ cell tumours (NSGCT) has been assessed by studying all
      patients presenting in the West of Scotland between 1975 and 1989. Between 1960
      and 1990, the number of testicular germ cell tumours registered has increased
      more than 2-fold; mortality rates have declined equally dramatically. Univariate
      and multivariate analysis of the data obtained on 440 patients with NSGCT showed
      age was not a prognostic factor influencing survival. 52 were patients over 40
      years at presentation; their 5 years survival was 71% compared with 79% in the
      younger patients (n = 388). This small survival difference is probably explained
      by the higher proportion of older patients treated before 1980. Treatment for
      this older group should be approached with the same curative intent as for
      younger patients and the same expectation of success.

PMID- 7577078
TI  - Epidermal growth factor receptor expression by northern analysis and
      immunohistochemistry in benign and malignant prostatic tumours.
AB  - Epidermal growth factor receptor (EGFR) expression in 44 benign prostatic
      hyperplasia (BPH) and 55 prostatic carcinoma specimens has been investigated
      using Northern blot analysis and immunohistochemistry. The values obtained for
      the EGFR mRNA in the BPH and carcinoma specimens were not significantly different
      and in the latter there was no correlation with grade. In the immunohistochemical
      assays, two antibodies to the external and one to the internal domain of EGFR
      were used. The former ones stained the basal cell membranes intensely whilst
      cytoplasmic staining of secretory epithelium was seen in BPH specimens with the
      latter. In the carcinoma specimens, the intensity of membrane staining correlated
      with the two external domain antibodies, r = 0.640, P < 0.001, but neither of
      these correlated with the EGFR mRNA results. All three antibodies demonstrated a
      trend towards elevated expression of EGFR with dedifferentiation which reached
      significance only with the internal domain antibody results, P < 0.02. No
      correlation was observed with tumour EGFR mRNA values and the EGFR
      immunohistochemical results. The EGFR immunoreaction with the external domain
      antibody in 14 treated high-grade tumours was comparable to that obtained in 15
      untreated anaplastic prostatic tumours. In 5 patients, both pre- and post
      treatment samples were available and these exhibited little or no difference in
      EGFR expression with therapy.

PMID- 7577079
TI  - Inhibition of mucin synthesis by benzyl-alpha-GalNAc in KATO III gastric cancer
      and Caco-2 colon cancer cells.
AB  - Previous studies from our laboratory have shown that benzyl-alpha-GalNAc inhibits
      the glycosylation of mucin in colon cancer cells. In this study, we determined
      whether benzyl-alpha-GalNAc inhibits mucin glycosylation in KATO III gastric
      cancer cells. We also examined its effects on expression of mucin antigens, and
      compared the mucins made by KATO III with those of a colonic cancer cell line,
      Caco-2. Results of these experiments suggest that benzyl-alpha-GalNAc (2 mM)
      inhibited [3H]glucosamine labelling of mucins by 82% in KATO III and by 70% in
      Caco-2. For both cell lines, the mucin secreted in the presence of benzyl-alpha
      GalNAc was less acidic. Both cell lines secreted benzyl-oligosaccharides, but
      those from KATO III (8-9 sugars) were larger than those from Caco-2 (6-7 sugars).
      In mucins purified from the medium of treated cells, peripheral carbohydrate
      antigens (sialyl Lex in KATO III and terminal fucose in Caco-2) were decreased
      (compared with control), while core carbohydrate antigens (T antigen in both cell
      lines and sialyl Tn in Caco-2) were increased. Western blots of cell homogenates
      showed differences between KATO III and Caco-2 in MUC 1 apomucin protein
      antigens, in sialyl Lex and in sialyl Tn antigens. We conclude that benzyl-alpha
      GalNAc does inhibit the glycosylation of mucin in KATO III gastric cancer cells
      as in human colon cancer cells, but that alterations in mucin antigens occur in a
      cell line-specific manner.

PMID- 7577080
TI  - Normal genetic response to gamma irradiation in familial adenomatous polyposis.
AB  - The present study, a co-operative project between three European institutes, was
      aimed at elucidating whether the APC gene in carriers of familial adenomatous
      polyposis coli (FAP) also causes some genetic sensitivity revealed by DNA damage
      and the yield of chromosome aberrations in peripheral blood lymphocytes exposed
      to gamma rays. In addition, it seemed of interest to study whether DNA repair is
      modified after irradiation of lymphocytes from FAP patients compared to controls.
      To this end, we have used the inhibition of the poly(ADP-ribose) polymerase
      (ADPRP) by 3-aminobenzamide (3ABA) and studied the effect of 3ABA on the
      frequency of DNA strand breaks and chromosome aberrations. The data indicate that
      FAP is not associated with an increased chromosomal sensitivity towards ionising
      radiation.

PMID- 7577081
TI  - High incidence of human papillomavirus in 146 cervical carcinomas. A study using
      three different pairs of consensus primers, and detecting viral genomes with
      putative deletions.
AB  - Polymerase chain reaction (PCR) primer sets and probe-cocktails were used for
      human papillomavirus (HPV) detection and typing of 146 fresh frozen biopsies of
      cervical carcinoma. We obtained a high detection rate (96%) by using three sets
      of consensus primer pairs directed at the L1 and E1 regions of HPV and by probing
      with a cocktail of random-labelled consensus and type-specific PCR products
      derived from HPV plasmids. In addition, we performed type-specific PCR
      amplification with E6-E7 primers. The procedure was designed to detect all HPV
      positive cases in a rapid, sensitive and specific way. In addition, by using
      different regions for amplification, we detected cases with putative genomic
      deletions in HPV. All the negative PCR and DNA isolation controls were negative.
      The six negative samples were negative with all probe-cocktails and type-specific
      primers and three of these negative samples were clear cell carcinomas. The
      detection rate was similar in squamous carcinomas and in adenocarcinomas and type
      16 was most common (65%) in both types of carcinoma. There were no double
      infections of human papillomavirus 16 and 18.

PMID- 7577082
TI  - Antitumour activity, toxicity and inhibition of thymidylate synthase of prolonged
      administration of 5-fluorouracil in mice.
AB  - Continuous infusions of 5-fluorouracil (5-FU) are increasingly used in the
      treatment of cancer. Their optimal use, however, has still to be determined since
      the availability of suitable animal models is limited. We studied continuous
      infusions in mice using subcutaneously implanted pellets that release 5-FU over a
      period of 3 weeks. At the maximum tolerated dose (MTD) (based on the systemic
      toxicity in healthy animals) we assessed the antitumour activity, haematological
      toxicity, inhibition of thymidylate synthase (TS) in tumours and the
      concentration of 5-FU in plasma during the 3-week period. We also studied the
      addition of leucovorin in different schedules. The dose-limiting toxicity was
      weight loss, and at the MTD of 10 mg of 5-FU released in 21 days per mouse
      myelosuppression was tolerable (nadir for leucocytes and thrombocytes was
      approximately 40% of pretreatment levels). In several independent experiments
      using the 5-FU-resistant Colon 26 tumour, a good antitumour activity was observed
      during the first part of the infusion, but thereafter the growth of the tumours
      resumed; the overall effect of continuous infusions was thus comparable to that
      of bolus injections. Coadministration of leucovorin did not enhance the
      therapeutic results; depending on the schedule used, it proved ineffective or
      only increased toxicity. Similar results were obtained with head and neck
      squamous cell carcinomas and with the 5-FU-sensitive tumour Colon 38. In Colon 26
      tumours the TS activity (FdUMP-binding assay) initially decreased to 20-30% of
      controls and returned to normal after 11 days. In the catalytic TS assay a slight
      inhibition was observed for the continuous infusion, followed after 11 days by a
      marked (4-fold) increase in activity. 5-FU plasma levels varied from 0.1 to 1
      microM following a circadian rhythm (with a peak at 6 h after light onset), and
      were maintained during the entire period. Subcutaneously implanted pellets
      represent a suitable model to study prolonged administration of 5-FU in mice and
      to evaluate the effect of modulating agents in laboratory animals before
      transferring data obtained in vitro to the clinic.

PMID- 7577083
TI  - Antitumour activity and retinotoxicity of ethyldeshydroxy-sparsomycin in mice.
AB  - The colony formation in agar of human tumour xenografts was used as a test system
      to study the cytostatic activity of ethyldeshydroxy-sparsomycin (EdSm) at the
      cellular level. EdSm was additionally studied in vivo in human tumour xenografts
      and murine tumour models. EdSm showed a clear dose-response effect in vitro. At
      continuous exposure with 0.01 micrograms/ml, 2 out of 11 of the tumours responded
      (a gastric and a small cell lung carcinoma). At 0.1 mu/ml EdSm, the tumour
      response was 5/11 tumours and at 1 microgram/ml the compound was active in all
      tumours. The maximal tolerable doses of EdSm in vivo have been determined in non
      tumour bearing CDF1 mice. In the intraperitoneally (i.p.) given multiple dose
      schedules the respective LD10 doses indicated that the tolerable cumulative dose
      increases when lower doses are given more frequently. This also enhances the
      antitumour activity in L1210 leukaemia to 172% T/C. On the other hand, continuous
      infusion strongly diminished the tolerable dose as well as the antitumour
      activity. EdSm was also active against i.p. inoculated P388 leukaemia (150% T/C),
      B16 melanoma (156% T/C), and RC carcinoma (197% T/C), and the subcutaneously
      (s.c.) inoculated L1210 (139% T/C) and RC (138% T/C). Absence of tumour responses
      was found in the following s.c. implanted murine tumours: M5076 sarcoma,
      osteosarcomas C22LR and CP369, and the LL carcinoma, as well as in the human
      tumour xenografts: LXFG 529, a non-small cell lung carcinoma; GXF 251, a gastric
      carcinoma; and FMa, an ovary carcinoma. Possible long-range retinotoxic effects
      of EdSm were investigated in tumour-bearing mice, cured after surviving treatment
      with LD50 doses of EdSm, by assaying the protein biosynthetic capacity of the
      retinal by assaying the ocular rhodopsin and opsin levels as parameters. In none
      of these cases could a significant reduction in either opsin or rhodopsin levels
      be measured and no changes were seen histologically.

PMID- 7577084
TI  - European School of Oncology position paper. Gene therapy for the medical
      oncologist.

PMID- 7577085
TI  - Spinal stabilisation in plasma cell disorders.
AB  - Five patients with plasma cell disorders and vertebral body lesions who presented
      with severe localised back pain associated with spinal instability are described.
      They underwent a total of six surgical spinal stabilisation procedures with
      excellent symptomatic relief. Spinal stabilisation was performed at presentation
      in 1 patient with a cervical spine lesion, and at sites of previously irradiated
      disease or recurrent disease in the other 4 patients. Stabilisation was achieved
      using various internal fixation techniques, and in 2 cases external fixation was
      obtained with a halo brace. The procedures were performed with minimal operative
      morbidity, and resulted in good symptom control. Spinal instability should be
      considered as a cause of severe localised back pain exacerbated by movement in
      patients with plasma cell disorders and vertebral body lesions. Operative spinal
      stabilisation should be considered as part of their management.

PMID- 7577086
TI  - Increased arterial inflow demonstrated by Doppler ultrasound in arm swelling
      following breast cancer treatment by Svensson et al., Volume 30, pp. 661-664,
      1994.

PMID- 7577087
TI  - Extra-ocular sebaceous gland carcinoma.

PMID- 7577088
TI  - Evaluation of Ki-67 expression as a prognostic feature in hepatocellular
      carcinoma in cirrhosis.

PMID- 7577089
TI  - Patterns of gastric cancer care by age. A registry-based study in Romagna, Italy.

PMID- 7577090
TI  - Different doses of epirubicin associated with fixed doses of cyclophosphamide and
      5-fluorouracil: a randomised study in advanced breast cancer.

PMID- 7577091
TI  - Non-cytotoxic CD4 tumour-infiltrating lymphocytes induce responses in patients
      with metastatic renal cell carcinoma previously treated with interleukin-2.

PMID- 7577092
TI  - Feasibility and compliance of epirubicin plus ambulatory continuous infusion
      ifosfamide at escalating doses in advanced soft tissue sarcomas: a phase I study.

PMID- 7577093
TI  - Protection of normal tissues from the cytotoxic effects of chemotherapy and
      radiation by amifostine (WR-2721): preclinical aspects.
AB  - Amifostine is a radioprotective agent that prevents radiation- and chemotherapy
      induced cellular injury through free-radical scavenging, hydrogen donation, and
      inhibition of DNA damage. Amifostine is metabolised and accumulated to a much
      greater extent in normal cells than in tumour cells. As a result, it exerts a
      protective effect from toxicity on normal tissues induced by chemo- or
      radiotherapy without reducing the antitumour effects of cancer therapy. Extensive
      preclinical studies have shown that amifostine protects against radiation damage
      and against the myelotoxic, nephrotoxic and neurotoxic effects of
      chemotherapeutic agents such as alkylating agents and platinum compounds. In some
      cases, the antitumour effects of these agents have been potentiated by
      amifostine. Amifostine has also been shown to protect against radiation- and
      chemotherapy-induced mutagenesis and, as a result, carcinogenesis. Use of
      amifostine allows for safer and more effective administration of radio- and
      anticancer therapy.

PMID- 7577094
TI  - Amifostine (WR-2721) protects normal haematopoietic stem cells against
      cyclophosphamide derivatives' toxicity without compromising their antileukaemic
      effects.
AB  - We compared the effects of amifostine (WR-2721) on the cytotoxicity of
      mafosfamide or 4-hydroperoxycyclophosphamide (4-HC) in normal marrow progenitor
      cells (CFU-GM) and leukaemic progenitor cells (CFU-L) during ex vivo purging for
      autologous bone marrow transplantation (ABMT). Mononuclear cells (MNC) were
      incubated with amifostine 3 mg/ml for 15 min, washed, and subsequently tested for
      their sensitivity to mafosfamide or 4-HC (20-200 micrograms/ 10(7) MNC/ml). The
      LD95 was significantly higher among amifostine-treated cells for PCM-CFU-GM in 6
      of 13 patients and for 5R-CFU-GM in 4 of 10 patients (P < 0.05). In contrast,
      amifostine exhibited no protective effects upon CFU-L. The results of this study
      will show that amifostine protects normal late and early progenitor cells for the
      toxic effects of cyclophosphamide derivatives while preserving their
      antileukaemic effects. These results suggest that amifostine has therapeutic
      value as a protective agent for normal marrow progenitor cells during ex-vivo
      purging of bone marrow for ABMT.

PMID- 7577095
TI  - Amifostine plus granulocyte colony-stimulating factor therapy enhances recovery
      from supralethal radiation exposures: preclinical experience in animals models.
AB  - A murine model was used to explore whether the cytoprotective agent amifostine
      (WR-2721) can be used to protect a critical fraction of haemopoietic stem cells
      against radiation, and whether granulocyte colony-stimulating factor (G-CSF) can
      then be used to stimulate the protected cells to proliferate and reconstitute the
      haematopoietic system. Groups of C3H/HeN mice treated with 200 mg/kg amifostine
      i.p. 30 min before 60Co irradiation and/or 125 micrograms/kg G-CSF subcutaneously
      from days 1-16 post irradiation were compared. The dose reduction factor (DRF) of
      the combination of amifostine and G-CSF from LD50/30 values was greater than the
      sum of the DRFs for amifostine and G-CSF individually. Acceleration of recovery
      bone marrow and splenic multipotent stem cells (CFU-s) and granulocyte-macrophage
      progenitor cells (GM-CFC), as well as of peripheral blood red and white cells and
      platelets, was greatest in mice treated with amifostine plus G-CSF. These studies
      suggest that amifostine and recombinant haematopoietic growth factors can be used
      in combination to reduce myelosuppression and lethality associated with radiation
      or radiomimetic drugs

PMID- 7577096
TI  - Protection of normal tissue from the cytotoxic effects of chemotherapy and
      radiation by amifostine: clinical experiences.
AB  - The clinical trials described in this review indicate that amifostine protects
      normal tissues from the toxicities of various antitumour regimens. In a
      controlled trial, pretreatment with amifostine reduced the frequency of
      cyclophosphamide-induced neutropenia. Comparisons of the effects of cisplatin
      with and without pretreatment with amifostine indicated that patients pretreated
      with amifostine had fewer nephrotoxic and neurotoxic effects and tolerated higher
      doses of cisplatin before the onset of neurotoxic effects. In a randomised trial,
      patients who received amifostine prior to treatment with cyclophosphamide and
      cisplatin discontinued chemotherapy because of haemato, nephro- or ototoxicity
      less frequently than patients treated with cyclophosphamide and cisplatin alone.
      Tumour response rates and survival were comparable in both groups indicating that
      amifostine selectively protects only normal tissues. A regimen of amifostine plus
      cisplatin and vinblastine followed by amifostine plus radiation in patients with
      non-small cell lung cancer revealed a 73% response to treatment. Other studies
      showed that amifostine protected against late radiation toxicity to pelvic organs
      without interfering with the antitumour effect of radiotherapy, and decreased the
      haematological and mucosal toxicity of combined treatment with cisplatin and
      radiation therapy.

PMID- 7577097
TI  - Preclinical pharmacology of docetaxel.
AB  - Docetaxel is a taxoid cytotoxic agent which promotes tubulin assembly into
      microtubles and inhibits their depolymerisation. In vitro, docetaxel reduces
      murine and human tumour cell survival by 50% at concentrations of 4-35 ng/ml,
      with a greater cytotoxic effect on proliferating than on non-proliferating cells.
      In vivo, docetaxel is schedule-independent. Over 80% of murine transplantable
      tumours were found to be very docetaxel sensitive, with complete regression of
      advanced stage tumours. Activity was also observed in > 90% of advanced stage
      human tumour xenografts in mice. In combination therapy studies, synergism with 5
      fluorouracil, cyclophosphamide and etoposide was observed in vivo. Docetaxel
      exhibited linear pharmacokinetics and long tumour retention in tumour-bearing
      mice; plasma protein binding ranged from 76 to 89%. In toxicological studies in
      mice and dogs, docetaxel produced haematological, gastrointestinal and neuromotor
      toxicity. The dog was found to be the most sensitive species to the toxic effects
      of docetaxel.

PMID- 7577098
TI  - An overview of phase II studies of docetaxel in patients with metastatic breast
      cancer.
AB  - Docetaxel is a new taxoid drug with good activity against human breast cancer
      cells in vitro; a number of partial and minor responses have been obtained during
      phase I studies in patients with advanced breast cancer. In phase II trials,
      first-line use of docetaxel has produced an overall response rate (OR) of up to
      73%. In addition, docetaxel has shown good activity when given as second-line
      therapy (OR 38%), particularly in patients with disease refractory to
      anthracyclines (OR 55%). Indeed, the high response rate in this latter group of
      patients clearly warrants further investigation of docetaxel in this setting.
      Neutropenia is the major dose-limiting toxicity of docetaxel, but other
      haematological effects are rare. Hypersensitivity and cutaneous reactions are
      ameliorated by premedication with corticosteroids and histamine antagonists;
      fluid retention may improve with longer use of prophylactic premedication.
      Docetaxel is mildly emetogenic, but no other premedication is necessary. In
      summary, docetaxel is an active new drug in the treatment of advanced breast
      cancer. Its role in the management of early stage disease awaits the results of
      prospective randomised trials.

PMID- 7577099
TI  - Docetaxel in advanced ovarian cancer: preliminary results from three phase II
      trials. EORTC Early Clinical Trials Group and Clinical Screening Group, and the
      MD Anderson Cancer Center.
AB  - Docetaxel has been evaluated in 293 patients with advanced ovarian cancer in
      three phase II trials. All patients had previously received cisplatin and/or
      carboplatin as first-line treatment. In all three studies, treatment comprised
      docetaxel 100 mg/m2 as a 1 h intravenous infusion every 3 weeks, without
      premedication for hypersensitivity reactions or emesis. To date, 200 patients are
      evaluable for response. Of these, 63 patients achieved complete or partial
      response, giving an overall response rate of 31.5% (95% confidence interval 24
      39%) for all evaluable patients, or 21.5% for all patients entered in the
      studies. Of the 57 patients whose disease had progressed either during previous
      therapy or within 4 months of discontinuing previous therapy, 13 (23%) responded
      to docetaxel (EORTC data). Major adverse effects of docetaxel observed in
      approximately half the patients (particularly those who received more than four
      courses) included skin reactions and fluid retention. Grade III or IV neutropenia
      was common but short-lived. Severe acute hypersensitivity reactions occurred in
      approximately 5% of patients. Docetaxel now warrants evaluation as part of first
      line therapy. Studies aimed at reducing the incidence of fluid retention and skin
      reactions with docetaxel are ongoing.

PMID- 7577100
TI  - Docetaxel in stage III and IV non-small cell lung cancer.
AB  - Phase II studies have been conducted to evaluate the efficacy and tolerability of
      docetaxel in the treatment of patients with advanced non-small cell lung cancer
      (NSCLC). Docetaxel was administered to patients with stage III and IV NSCLC at a
      dose of 100 mg/m2 intravenously over 1 h every 3 weeks. Patients included in
      these four phase II studies had received either no prior chemotherapy (n = 114)
      or treatment with cisplatin- or carboplatin-containing regimens (n = 57). Major
      objective response rates were reported in 33-38% of previously untreated
      evaluable patients and in 21-27% of previously treated evaluable patients.
      Neutropenia was the most common adverse event. Non-haematological adverse events
      included hypersensitivity reactions, skin rash, alopecia and fluid retention.
      Docetaxel demonstrates significant antitumour activity in patients with advanced
      NSCLC. Further investigations of this agent with corticosteroid premedication,
      colony-stimulating factors and other agents active in NSCLC are indicated.

PMID- 7577101
TI  - Phase II studies of docetaxel in the treatment of various solid tumours. EORTC
      Early Clinical Trials Group and the EORTC Soft Tissue and Bone Sarcoma Group.
AB  - Docetaxel has been evaluated in six tumour types in a total of 189 patients
      entered into phase II studies. Treatment consisted of a 1 h intravenous infusion
      of docetaxel 100 mg/m2 repeated every 3 weeks. No premedication was administered
      for possible hypersensitivity reactions. Docetaxel was found to be effective as
      first-line chemotherapy for head and neck cancer (response rate 44%) gastric
      cancer (23%) and melanoma (14%) and as second-line chemotherapy for soft tissue
      sarcomas (21%; 95% confidence interval: 7.5%-43.7%). The results in colorectal
      and renal cancer were disappointing, with response rates of less than 10%. The
      most frequent adverse effects were alopecia (81%), grade III-IV leukocytopenia of
      short duration (66%) and skin reactions (52%). Hypersensitivity reactions were
      mild and occurred in 26% of patients. Docetaxel is an important new drug in the
      treatment of solid tumours.

PMID- 7577103
TI  - [Anatomopathologic changes in the distal esophagus following proximal gastric
      vagotomy. Experimental study].
AB  - In order to determine the causes of postvagotomy dysphagia, we examined
      microscopic changes in the lower esophagus after a proximal gastric vagotomy.
      Forty dogs were divided into 4 groups (n = 10). Group I was used as control. In
      group II, the effect of denervation was studied by means of transthoracic
      vagotomy. In group III, the effect of mechanical traction of the lower esophagus
      was studied, without denervation or surgical manoeuvres. In group IV, the effect
      of denervation, esophageal traction and the surgical manoeuvres, of proximal
      gastric vagotomy was examined. No periesophageal hematomas or fibrosis was found.
      Degenerative nerve phenomena were found with no significant differences in the
      three groups. In groups III and IV, lesions of the esophageal muscular layer were
      observed, without significant differences. Chronic inflammatory changes and
      fibrosis were also encountered being more intense and significantly more frequent
      in group IV. We conclude that the surgical manoeuvers necessary to obtain
      denervation of the cardioesophageal function during proximal gastric vagotomy,
      could be responsible for the appearance of post-vagotomy dysphagia.

PMID- 7577102
TI  - Early clinical studies with docetaxel. Docetaxel Investigators Group.
AB  - Docetaxel has been evaluated in six phase I studies involving a total of 234
      patients with a wide variety of tumour types (50% had breast or ovarian cancer).
      The aims of these studies were to determine the optimal dosage schedule of
      docetaxel for use in subsequent phase II studies, and to characterise the
      pharmacokinetic and tolerability profiles of docetaxel. Intravenous (i.v.) doses
      of docetaxel (5-115 mg/m2) were administered in various treatment schedules for a
      total of 790 courses. Cycles were repeated every 2-3 weeks. Dose-dependent
      neutropenia was the major dose-limiting adverse effect of docetaxel. Other
      adverse events reported included hypersensitivity, fluid retention, skin
      reactions, asthenia and alopecia. Anaphylactoid reactions occurred rarely. No
      abnormal cardiac activity was detected, and neurological adverse events were
      mild. Docetaxel 100 mg/m2 administered as a 1 h i.v. infusion every 3 weeks
      combined acceptable tolerability with complete neutropenic recovery. This dosage
      schedule was thus considered to be optimal for further investigation in phase II
      studies.

PMID- 7577104
TI  - [Value of endoscopy in the diagnosis of postoperative gastritis caused by
      alkaline reflux].
AB  - OBJECTIVE: A long term retrospective study comparing endoscopic lesions and their
      relationship with symptoms and histological lesions of postoperative Alkaline
      Reflux Gastritis (ARG) between partial gastrectomy Billroth II (n = 25) and the
      Roux-en-Y (n = 36) is presented. PATIENTS AND METHODS: In patients operated on
      with both techniques the clinical, endoscopic and histological aspects are
      studied. RESULTS: The patients operated on with the Billroth II technique present
      a higher frequency of bile in the gastric remnant and mucosal lesions in the
      endoscopic study (p < 0.001) compared with the Roux-en-Y group. Bile and mucosal
      lesions on the gastric stump are more common with symptoms and histological
      lesions of postoperative ARG. CONCLUSIONS: The endoscopic evaluation is a valid
      and reliable examination in the diagnosis and follow up of postoperative ARG.

PMID- 7577105
TI  - [Somatostatin and growth hormone in post-colectomy intestinal hyperplasia in
      rats].
AB  - AIM: Somatostatin exerts significant effects on gastrointestinal function that
      may include mucosal growth regulation, probably through its action on growth
      hormone release. The aim of this work was to correlate somatostatin and growth
      hormone plasma levels and the hyperproliferative status of intestinal mucosa
      after colectomy. EXPERIMENTAL DESIGN: Adult Wistar rats were divided into two
      groups: control sham operated (n = 8) and large bowel resection (n = 8). Seven
      days post-colectomy, the animals were killed. Ileal mucosal samples were assayed
      for proliferative status (morphometry, and proliferating cell nuclear antigen
      labeling) and blood samples for plasmatic somatostatin and growth hormone
      measurement. RESULTS: A hyperproliferative status was observed with significant
      increases in villous length and crypt proliferating cell nuclear antigen
      labeling. Plasma somatostatin showed a 95% significant decrease while growth
      hormone levels increased significantly. CONCLUSION: The intestinal adaptation
      seen after colectomy is associated with lower somatostatin and higher growth
      hormone plasma level, possibly by regulating the intestinal adaptative process.

PMID- 7577106
TI  - [Treatment with sulindac of adenomatous polyps in familial polyposis].
AB  - BACKGROUND: The effect of sulindac, a nonsteroid antiinflammatory drug, has been
      reported to cause both regression and suppression of colon polyps in patients
      with familial adenomatous polyposis and Gardner's syndrome. We report our
      experience with seven patients with diffuse colonic polyposis treated with
      sulindac. PATIENTS AND METHODS: Seven patients with familiar adenomatous
      polyposis, four men and three women (mean age, 30 years; range 16 to 41 years)
      were included in this study. Two patients that underwent prior colectoctomy with
      ileorectal anastomosis and had polyps in the rectum were also included. The
      polyps ranged in size from 0.2 to 2.5 cm; most of them were less than 1 cm.
      Sulindac was given 150 mg. twice a day. Further colonoscopic examination was done
      at 6-month intervals during follow-up in all patients. RESULTS: A disappearance
      or a marked reduction in the number and size of polyps was observed in all
      patients after 24 months of treatment with sulindac. The drug was well tolerated
      and no side effects were observed during treatment. CONCLUSION: The authors
      conclude that sulindac is effective in inducing the regression of rectal polyps
      in familial, adenomatous polyposis.

PMID- 7577107
TI  - [Prevalence and clinical significance of autoantibodies in chronic hepatitis C
      treated with interferon alfa].
AB  - Autoantibodies against non organ-specific may be induced by IFN treatment in HCV
      liver chronic disease. In order to assess this issue and its clinical
      significance, 44 patients with chronic hepatitis C (anti HCV and RNA-HCV +)
      treated with IFN were evaluated. In 13 patients (29.5%) the following
      autoantibodies were detected during the treatment: AAML (5), AAN (9), ALK-M (4).
      Only in the A-LKM + patients there was a slight increase in aminotransferases
      with a reappearance of the viremia. Moreover 2 of these patients showed a flare
      of their liver disease without systemic findings. During the follow up (28)
      months one of the patients normalized the aminotransferases with clearance of
      serum HCV RNA. There were no statistical differences in the sustained response
      rate between patients with (2/13) or without (4/31) autoantibodies. The
      development of AAN, AAML and ALKM at low titer during IFN treatment in CH-C is
      without clinical relevance. However, ALKM detection is occasionally associated
      with the "breakthrough" phenomenon with HCV eradication, suggesting an immuno
      modulatory activity of IFN.

PMID- 7577108
TI  - [Biomaterials and hernia surgery. Rationale for using them].
AB  - A study was made of the distinct biomaterials used in surgery and the
      requirements to be fulfilled and principles applied for their use in the repair
      of abdominal wall hernias. The biomaterials most frequently used in hernia
      surgery are: politetrafluorethylene (PTFE) sheet (Gore-Tex), the multifilament
      PTFE mesh (Teflon), the multifilament polypropylene mesh (Surgipro), the mono
      filament polypropylene mesh (Marlex), the double filament polypropylene mesh
      (Prolene) and the multi-filament polyester mesh (Mersilene). Requirements for use
      in hernia surgery: the material must be inert, permanent and non-reabsorbable,
      resistant to infection, becomes rapidly fixed and incorporated into the host
      tissues, and not adhere to abdominal viscera. Principles for use: based on the
      overlapping of the mesh with the aponeurotic plane such that abdominal pressure
      aids fixation to this plane; contact with abdominal viscera must be avoided.
      CONCLUSIONS: based on the published experimental and clinical experience of the
      authors and other researchers, polypropylene is judged to be the most appropriate
      material for the repair of abdominal hernias.

PMID- 7577109
TI  - [Deep cystic enteritis in Peutz-Jeghers syndrome (pseudoinfiltrating lesions in a
      patient with enteric polyps)].
AB  - We report a case of enteritis cystica profunda observed in a patient who, owing
      to both his personal and familial history, had been diagnosed and suffering from
      Peutz-Jeghers syndrome. The patient was operated because of a clinical picture of
      intestinal invagination. Together with hamartomatous polyps, anatomopathological
      study of the segment of the small intestine removed revealed the presence of
      lesions typical of Enteritis cystica profunda consisting in the presence of
      benign encysted glands and pools of mucous in the deep layers of the intestinal
      wall. The main characteristics of this interesting and rare entity are briefly
      commented.

PMID- 7577110
TI  - [Hepatic actinomycosis: radiologic findings and percutaneous drainage].
AB  - We report a case of hepatic actinomycosis in a woman with previous duodenal
      ulcer. The findings of ultrasound, computed tomography and abscess imaging are
      presented. The diagnosis was made by thin needle aspiration biopsy under computed
      tomography guidance. The treatment consisted in percutaneous drainage and
      intravenous antibiotic therapy.

PMID- 7577111
TI  - [Acalculous cholecystitis and intestinal cryptosporidiosis: frequent association
      in HIV patients].
AB  - Five cases of acalculous cholecystitis associated with Cryptosporidium intestinal
      infection in HIV infected patients are reported. Clinical, Biological and
      Microbiological features as well as imaging studies are described. All the
      patients were males. Risk factors for HIV infection included previous I.V. drug
      abuse (3), homosexuality (1) and unknown (1). On admission a similar history of
      weight loss, fever, abdominal pain, diarrhea, anorexia and asthenia, together
      with biological data of cholestasis, was present in all patients. Ultrasound
      studies showed a distended gallbladder without calculi and a thickened wall, the
      bile duct being dilated in four of five cases. Cryptosporidium were found in
      stool specimens of all patients as well as histologically in one of two patients
      who underwent surgery while CMV was shown in the other one. Endoscopic retrograde
      cholangiography was performed in four cases showing a congestive, edematous and
      protruded papila in three patients, being normal in the fourth with a choledocal
      stenosis.

PMID- 7577114
TI  - [Desmoid tumor: a simple problem with severe sequelae].
AB  - Desmoid tumours are rare benign lesions with an important local invasive
      potential and high risk of recurrence. The reported incidence is low, and the
      diagnosis is made in young women with an abdominal mass. Estrogen levels, a
      history of trauma and Gardner's syndrome have been incriminated. The defect of
      the entire thickness of the abdominal wall was reconstructed with a graft of
      marlex in three cases. The aggressive behavior of these three cases, and
      diagnosis of eight extraperitoneal cases in a short period of two years prompted
      us to review the features of the disease.

PMID- 7577112
TI  - [Acute pancreatitis associated with hepatotoxicity induced by amoxicillin
      clavulanic acid].
AB  - A 25-year old man suffered from acute pancreatitis and cholestatic acute
      hepatitis simultaneously after 4 weeks of an antibiotic treatment withdrawal
      (amoxicillin plus clavulanic acid) which was given for pharyngitis. Other
      potential etiological causes of both acute pancreatitis and liver disease, were
      excluded. The causal relationship between amoxicillin plus clavulanic acid and
      cholestatic hepatitis is well know, but no data has been reported regarding acute
      pancreatitis. The medical literature is reviewed and the mechanisms of toxicity
      are discussed.

PMID- 7577115
TI  - [Vaccination against hepatitis A virus. Is it worthwhile?].

PMID- 7577116
TI  - [Dysphagia caused by Forestier disease and periosteophytic hematoma].

PMID- 7577113
TI  - [Digestive hemorrhage and hemoperitoneum as complications of visceral aneurysms].
AB  - Two cases of visceral aneurysm are reported, one of the splenic artery and
      another of the gastroepiploic artery. The reason for the publication is the
      rarity, especially of aneurysms of the gastroepiploic artery, and because of the
      unusual presentations as upper gastrointestinal hemorrhage and hemoperitoneum
      respectively. The splenic artery aneurysm was diagnosed by CAT scan and the
      gastroepiploic one during emergency laparotomy because of the hemodynamic
      disturbance.

PMID- 7577117
TI  - [Bleeding duodenal varices].

PMID- 7577118
TI  - [Treatment of recurrent Isospora belli diarrhea].

PMID- 7577119
TI  - [Changed hepatic vein flow in patients with cirrhosis. A Doppler study of hepatic
      veins in patients with cirrhosis].
AB  - OBJECTIVE: To evaluate the changes in the Doppler waveform of the hepatic veins
      in patients with cirrhosis. DESIGN: We analyzed prospectively with Doppler
      ultrasound the flow of the hepatic veins and we compared the different Doppler
      waveform patterns with the degree of liver failure according to the Child-Pugh
      score. PATIENTS: Forty three patients with cirrhosis and 60 normal individuals
      with similar age and sex. RESULTS: Abnormal hepatic vein waveforms were found in
      40 of 43 patients with cirrhosis and in none of the 50 controls subjects. No
      statistically significant differences were detected between the different Doppler
      waveform patterns and the Child-Pugh score (p = 0.063). CONCLUSIONS: Our findings
      indicate that an alteration of the Doppler waveform pattern of hepatic veins
      suggest the presence of cirrhosis and that there is no association between the
      degree of the liver failure and the waveform patterns.

PMID- 7577120
TI  - [Neoplastic obstructive jaundice: palliative treatment with self-expandable
      metallic prosthesis].
AB  - PURPOSE: Study of the effectiveness and morbidity of palliative treatment of
      malignant obstructive jaundice with metallic biliary endoprosthesis compared to
      surgical palliation. DESIGN: Retrospective review. PATIENTS: 35 patients with non
      resectable neoplasms causing jaundice were treated with percutaneous stent
      (pancreatic carcinoma, n = 11; cholangiocarcinoma, n = 11; gallbladder carcinoma,
      n = 4; extrahepatic metastases of various malignancies, n = 8). CONTROL GROUP: 23
      patients with malignant jaundice treated with palliative surgery. RESULTS: Most
      frequent complications were cholangitis and stent obstruction. The mean hospital
      stay after the stent placement was 6.8 days, longer in patients with
      complications (p = 0.035). Recurrence of jaundice was seen in 22.9% of the
      patients and the rate of readmission was 42.9%. The mean survival was 163.33 days
      (range 19-522). Reduction in serum bilirubin after BE was significant (215 vs. 82
      mmol/l, p < 0.001). CONCLUSIONS: Comparing to our previous experience with
      surgical palliative treatment, there was no significant difference neither in
      morbidity-mortality, nor recurrence or readmission. Patients with pancreatic
      cancer and cholangiocarcinoma benefit from a shorter hospital stay.

PMID- 7577122
TI  - [Early bile drainage in acute cholangitis].
AB  - OBJECTIVE: We have studied the impact of early biliary drainage (surgical or
      endoscopical) on morbidity-mortality of acute cholangitis. PATIENTS AND METHODS:
      During a five-year period (1988-1992) 106 patients were diagnosed of acute
      cholangitis (clinically, echographically and microbiologically). RESULTS:
      Surgical intervention was performed in 78% of the patients, endoscopic biliary
      drainage in 18% and in 4% medical treatment alone. In 65% of cases, biliary
      drainage was performed during the eight hours after diagnosis. Overall mortality
      rate was 3, 7% (4 patients). CONCLUSIONS: Our results suggest that early biliary
      drainage of acute cholangitis is the most important factor in order to achieve a
      low mortality rate.

PMID- 7577123
TI  - Clinical value of an automated granulocyte elastase assay in predicting severity
      of acute pancreatitis.
AB  - OBJECTIVE: Quantification of circulating levels of granulocyte elastase has been
      shown to be a reliable method to predict severity of acute pancreatitis. The
      ELISA method until now available is, however, not easily applicable to the
      clinical routine. MATERIAL AND METHODS: In the present study we analyzed,
      retrospectively the clinical usefulness of an automated granulocyte elastase
      assay, the immunoactivation (IMAC) procedure, in predicting the course of acute
      pancreatitis, and we compared it with the ELISA method. PATIENTS: Plasma samples
      from 39 patients with acute pancreatitis, 18 with mild episodes and 21 with
      severe disease, were analyzed for granulocyte elastase concentration by both
      automated and manual ELISA procedures, on admission and on days 1, 2, 3, 5, 7 and
      10. RESULTS: Automated elastase values did not differ statistically (Mann-Whitney
      test) from manual granuloma elastase values obtained by ELISA. Higher plasma
      elastase concentration was invariably found in severe pancreatitis when compared
      to mild cases. The optimal discriminating (severe vs mild illness) cutoff values
      were 200 micrograms/L on admission and 250 micrograms/L at 24 hours. Both assays
      showed similar prognostic reliability upper 90 per cent. CONCLUSIONS: Automated
      procedures enable faster and simpler granulocyte elastase determinations and
      exploit the benefits of this early and efficient prognostic marker.

PMID- 7577121
TI  - [Development of spontaneous bacterial peritonitis in an experimental model in
      cirrhotic rats. Relationship with intestinal bacterial translocation].
AB  - Spontaneous bacterial peritonitis (SBP) is one of the most important complication
      in cirrhotic patients with ascites, but is pathogenesis is not well known. It is
      thought that the impaired host defences and the passage of enteric bacteria into
      the mesenteric lymph nodes, named bacterial translocation, may be two important
      mechanisms in the pathogenesis of SBP. We have studied this phenomenon in an
      experimental model with oral CC14 induced cirrhotic rats. SBP occurred in 36% of
      ascitic rats, all cases being produced by enteric Gram (-) bacteria. Bacterial
      translocation was observed in 100% of rats with SBP but in 53% of rats without
      SBP (p < 0.05). In all cases the same organism was isolated in ascitic fluid and
      in mesenteric lymph nodes. These results suggest that bacterial translocation
      could play an important role in the pathogenesis of SBP.

PMID- 7577124
TI  - [Epidemiology of exocrine pancreatic cancer in the Principality of Asturias, 1973
      1992].
AB  - Pancreatic adenocarcinoma continues increasing in frequency, its diagnosis is
      usually realized very late and the results of the surgery, that is the only
      possibility of cure, gives often a feeling of frustration. During the period
      between 1973 and 1992, 1032 patients were diagnosed of pancreatic carcinoma at
      the different hospital institutions of our region. The incidence has increased
      from 1.28 to 6.42 cases/100,000. The proportion male/female was 1.5/1. Mean age
      of the patients was 67.5 +/- 11.35 and the median age was 65 years. In relation
      with the sex, the women age was higher: 70.2 +/- 11.81 (p < 0.01). The best
      diagnostic test was the CAT scan with 87.5 sensitivity. The overall resectability
      rate was low (11%), but there is a large difference between the beginning and the
      end of the period (6.8% and 14.1% respectively). Staging of the disease was stage
      IV in 36.4% of the cases. The 66.5% of the patients underwent palliative surgery.
      Cholecystojejunostomy was the most frequent operation. It wasn't possible any
      surgical management at the 3.5% of the cases cause of the disease was very
      extended; laparotomy was the only method used in 18.7%. The average survival rate
      with exeresis surgery was 18 months; with palliative surgery, it was only of
      eight months. The natural history of pancreatic carcinoma was situated at 5.57 +/
      2.63.

PMID- 7577125
TI  - [Mesenteric lipodystrophy].
AB  - Mesenteric lipodystrophy is a rare disorder characterized by either focal or
      diffuse thickening of the mesentery due to chronic inflammation and fibrosis. The
      etiology and pathogenesis is obscure. Roentgenologic findings help in
      differential diagnosis with other diseases but they rarely establish the
      diagnosis. This is made in most cases by laparotomy.

PMID- 7577126
TI  - [Esophageal intramural pseudodiverticulosis].
AB  - Esophageal intramural pseudodiverticulosis is an uncommon and benign primary
      disease of the esophagus. Less than 150 cases have been reported. We report a new
      case diagnosed by endoscopy during the investigation of an upper gastrointestinal
      bleeding, in a 48-year-old man who was assymptomatic from the esophageal point of
      view. We discuss the clinical, pathogenic, diagnostic and therapeutic aspects of
      this disease.

PMID- 7577127
TI  - [Tracheoesophageal fistula secondary to endoscopic sclerotherapy of esophageal
      varices].
AB  - Over the past 15 years, endoscopic variceal sclerotherapy (EVS) has become the
      main therapy for patients with bleeding esophageal varices. EVS has the advantage
      of a low associated mortality and morbidity, but may lead to serious
      complications. We report a case of esophagotracheal fistula complicating
      sclerotherapy that resolved with nonsurgical management.

PMID- 7577131
TI  - [Peritoneal pseudomyxoma and liver metastasis].

PMID- 7577130
TI  - [Acute hepatitis due to ingestion of Ecstasy].
AB  - "Ecstasy" or 3,4-methylenedioxymethylamphetamine, is a synthetic amphetamine
      which is increasingly consumed in Spain as a "recreational" drug. It has been
      associated with serious medical and psychiatric side effects, though, it is
      popularly considered, as a non dangerous drug. The development of acute hepatitis
      associated with the use of "ecstasy" has been reported by other authors from
      areas where its use is widely spread. We report the development of acute
      hepatitis associated with use of "ecstasy" in a young man with successful
      recovery and spontaneous resolution. In other cases the acute hepatitis may have
      a torpid evolution with slow resolution, fulminant liver failure, and death with
      hepatic encephalopathy, disseminated intravascular coagulation and adult distress
      syndrome. An idiosyncratic toxic hepatitis might be due to either 3,4
      methylenedioxymethylamphetamine or a metabolite, a contaminant in 3,4
      methylenedioxymethylamphetamine manufacture, or to an additive in tablet or
      capsule formulation.

PMID- 7577129
TI  - [Mucinous adenocarcinoma of the anal region. Study of 4 cases].
AB  - OBJECTIVE: We report 4 cases of a special anal tumor featuring a long history of
      inflammatory signs and fistulas in that area. DESIGN: A retrospective study from
      the histologic diagnosis back to the first symptom and up to the last follow-up
      or death. PATIENTS: We studied all patients with a histologic diagnosis of
      mucinous adenocarcinoma of the anus admitted to our hospital. RESULTS: All of
      them showed a long history of anal inflammatory signs and/or fistula before
      diagnosis. In all cases, the tumors were mucinous adenocarcinomas with minimal
      cytologic atypia. Of the 4 patients, one is dead, and we have lost the follow-up
      of another one 13 months after surgery when he had no evidence of recurrence.
      CONCLUSIONS: In every patient with a long-standing anal fistula or a recurrent
      anal abscess, a biopsy is mandatory to rule out an underlying low grade mucinous
      carcinoma and if it shows a low grade mucinous adenocarcinoma, the treatment of
      choice will be local resection if it is available. If not, an abdominal perineal
      resection showed be done without hesitation.

PMID- 7577128
TI  - [Synchronous intestinal, tonsillar and pulmonary tuberculosis].
AB  - OBJECTIVES: To emphasize the unusual synchronous presentation of intestinal,
      pulmonary and tonsillar tuberculosis in the same patient. CLINICAL CASE: A 43
      years old male consults for abdominal pain and alternating episodes of diarrhoea
      constipation. Based on radiologic, endoscopic and pathologic studies the
      diagnosis of Crohn's ileo-cecal disease is achieved and a treatment with
      salazosulphapyridine and corticosteroid is started. Two months later the patient
      presents with a tonsilar ulceration that is diagnosed as tuberculosis on biopsy
      material. At the same time, chest x-rays film reveal active tuberculous lesions,
      and tuberculous bacili are seen in the sputum. Simultaneously the intestinal
      disease worsens and complicates with incomplete occlusion that requires a right
      hemicolectomy. Pathologic study of the specimen shows evident tuberculous
      lesions. Specific treatment for tuberculosis is started, and the patient remains
      free of disease one year later. CONCLUSIONS: Due to the increase in the
      prevalence of tuberculous diseases, we must keep it in mind in the differential
      diagnosis of intestinal strictures, even though they are suggestive of Crohn's
      disease, and a radical surgical procedure must also be evaluated.

PMID- 7577133
TI  - [Giant diverticulum of the sigmoid colon].

PMID- 7577134
TI  - [Colonic carcinoma with epidermoid differentiation].

PMID- 7577135
TI  - [A case of systemic lupus erythematosus associated with cerebral infarction and
      cerebral hemorrhage].
AB  - This is a report of cerebral infarction and cerebral hemorrhage derived from
      systemic lupus erythematosus. A 49-year-old male was admitted to our hospital due
      to dysarthria and supranuclear facial palsy. He had been suffering from SLE and
      medicated incompletely since 9 years prior to admission. A CT scan showed a small
      infarction in the left parietal area. An angiography revealed a tapering stenosis
      of the left carotid siphon and an occlusion of the left vertebral artery at the
      cisternal portion. On the 13 days after the admission, he complained of a high
      fever and right hemiparesis. The CT scan disclosed newly multiple small
      infarctions in the left parietal area. The angiography showed the progressing of
      the tapering stenosis at the left carotid siphon, and demonstrated the narrowing
      of the left superior temporal artery and ophthalmic artery in addition to the
      disappearance of a left posterior communicating artery. High dose of steroid was
      given to him, but cerebral hemorrhage and huge left cerebral infarction were
      complicated. On the 26 days after the admission, his general condition was
      worsened and died. It was considered that the cerebral infarction and hemorrhage
      might be derived from the vasculitis of SLE.

PMID- 7577136
TI  - [A 78-year-old woman who had an onset of seizure and right hemiparesis at the age
      77].
AB  - We report a 78-year-old woman who had an onset of convulsion and right
      hemiparesis at the age 77. She had been well until October 28th of 1990 when she
      suddenly developed a seizure starting in her right face with secondary
      generalization. She was admitted to Saitama Kyodo Hospital where neurologic
      examination revealed confusion with slight right hemiparesis; deep reflexes were
      exaggerated on the right side; otherwise neurologic examination was unremarkable.
      Cranial CT scan revealed an iso-density mass in the left motor area with
      extensive edema extending into left anterior frontal as well as parietal regions;
      by contrast enhancement, a homogeneous enhancement of the tumor was noted. She
      was treated with glycerol and phenytoin, and she became alert two days after her
      admission. The diagnosis of metastatic brain tumor was entertained; extensive
      malignancy survey was performed, however, no primary tumor was found. As
      neurosurgical procedure was refused, she was discharged on December 16th of 1990.
      She noted worsening of her right hemiparesis in the end of February, 1991, and
      she was admitted again on March 18th of 1991. On neurologic examination, she was
      disoriented to time and place; she was apparently demented. Her right hemiparesis
      was more advanced and she was unable to walk. Her hospital course was complicated
      by disturbance of consciousness and pneumonia, and she died on August 22nd of
      1991. The patient was discussed in a neurological CPC. Opinions were divided
      between meningioma and a metastatic brain tumor. Other possibilities raised
      included malignant lymphoma and glioblastoma multiforme. As edema was very
      extensive on CT, many participants thought that it might be a metastatic brain
      tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577137
TI  - [Clinical picture of DRPLA].

PMID- 7577132
TI  - [Erythromycin: an alternative in conservative management of Ogilvie syndrome].

PMID- 7577138
TI  - [Machado-Joseph disease].

PMID- 7577139
TI  - [Neuropathology of dentatorubral-pallidoluysian atrophy and Machado-Joseph
      disease].

PMID- 7577140
TI  - [Molecular genetics of hereditary spinocerebellar ataxia].

PMID- 7577141
TI  - [Effects of the nitric oxide donor SIN-1 on the membrane potential of mouse
      neuroblastoma-rat glioma hybrid cells].
AB  - The effect of the nitric oxide donor SIN-1 on the membrane potential of cultured
      mouse neuroblastoma-rat glioma hybrid NG108-15 cells was investigated using the
      whole cell patch method. It has been reported that neurite formation can be
      induced in NG108-15 cells by adding of dibutyryl cyclic AMP to the culture
      medium. Using this system we found that SIN-1 has a selective inhibitory effect
      on the membrane potential of the calcium current which is concentration-dependent
      in the 1 mu M-100 microM range. This effect was transient and reversible, the
      same as seen with the calcium channel blocker nilvadipine at concentrations of 10
      microM to 10 microM. At higher concentrations, ranging from 500 microM to 1 mM,
      however, SIN-1 also caused prolonged inhibition of the membrane potential of the
      sodium current. However, this effect was also reversible. These findings suggest
      that SIN-1 has a reversible inhibitory action on the membrane potentials of
      neurons.

PMID- 7577142
TI  - [Antitumor effect of MX2, a new morpholino anthracycline against C6 glioma cells
      and its combination effect with photodynamic therapy in vitro].
AB  - MX2, a new lipophilic morpholino anthracycline, has been reported to have
      superior chemotherapeutic effects to adriamycin against murine and human tumor
      cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells
      was examined as well as the photocytotoxicity of MX2 and the combination effect
      of MX2 and photodynamic therapy (PDT) in vitro. Colony formation is inhibited
      even with only 2 hour treatment with MX2 in a dose-dependent manner. In this
      colony forming efficiency assay the drug concentration required for 50%
      inhibition of colony formation for C6 glioma cells was 24.0 +/- 4.5 ng/ml. Mild
      photocytotoxicity of MX2 against C6 glioma cells was observed at a high
      concentration (100 ng/ml) of MX2 following exposure to white light but not red
      light. In combination, MX2 and the photosensitizer haematoporphyrin derivative
      (HpD) exhibited an additive cytotoxic effect against C6 glioma cells when the
      cells were treated with MX2 either immediately after red light illumination
      following incubation with HpD or at an interval of 24 hours before incubation
      with HpD. We conclude that MX2 may be clinically useful against malignant glioma
      alone, and in combination with other therapies such as PDT.

PMID- 7577143
TI  - [Cerebral blood flow increase and P300 latency prolongation by intravenous
      injection of acetazolamide--investigation in lacunar cerebral infarction and
      healthy subjects].
AB  - The cerebral blood flow and the P300 were measured before and 20 minutes after
      intravenous injection of 17 mg/kg acetazolamide in 15 cases of lacunar cerebral
      infarction and 10 healthy subjects. In cerebral infarction, the study was
      performed within 2 weeks after the onset. The cerebral blood flow except the
      infarcted area was increased significantly by the intravenous injection of
      acetazolamide in the lacunar cerebral infarction group and the healthy subject
      group. The blood flow decrease around the infarcted area (intracerebral steal
      phenomenon) by the intravenous injection of acetazolamide was not observed in any
      case. The N200 latency and the P300 latency were prolonged significantly by the
      intravenous injection of acetazolamide in the lacunar cerebral infarction group
      and in the healthy subject group but the N100 latency and the P200 latency did
      not show any significant changes. Despite the increase in cerebral blood flow,
      cerebral function may be decreased by intravenous injection of acetazolamide.

PMID- 7577144
TI  - [Kinetics of glucose metabolism in central neurocytomas].
AB  - To estimate proliferating activity of central neurocytoma, we measured kinetic
      rate constants and glucose metabolic rate (kinetic-rCMRGI) using dynamic positron
      emission tomography (PET), as well as autoradiographic rCMRG1 (arg-rCMRG1), in
      patients with histologically verified central neurocytoma. The subject included
      five patients, four males and one female, aged from 23 to 53 years with a mean
      age of 41 years old. All tumors were located in the lateral ventricle and two
      extended into the third ventricle through the forearm of Monro. Tumor lesion on
      the PET images was determined using CT or MRI, which was performed at levels
      equivalent to those for the PET scans. The kinetic rate constants of tracer
      transport from blood to brain (k1), reverse transport from brain to blood (k2),
      and phosphorylation (k3) were analyzed according to the three compartment 18F
      fluorodeoxyglucose (FDG) model. For quantitative analysis, regions of interest
      (ROI) on PET images were delineated on the tumor and the contralateral gray
      matter. Tumor k1 and k2 values were similar to or higher than those of the
      contralateral gray matter, suggesting high permeability due to lack of blood
      brain barrier. Tumor k3 value, an indicator of hexokinase activity, and kinetic
      rCMRG1 were exceedingly lower in three of five patients. These three patients
      have been free from tumor recurrence or regrowth, postoperatively. The other two
      patients, tumor kinetic-rCMRG1 was similar to or higher than that of the
      contralateral gray matter. One patient suffered from tumor regrowth shortly after
      resection, and the other has been followed up postoperatively. Thus, k3 and
      kinetic-rCMRG1 are indicative parameters of proliferative activity in central
      neurocytoma.

PMID- 7577145
TI  - [Interhemispheric differences of the middle latency auditory evoked magnetic
      fields revealed by a whole head magnetoencephalography system].
AB  - It is known that the auditory evoked N100m response appears faster in the
      contralateral hemisphere than in the ipsilateral hemisphere to the stimulated
      ear. For the middle latency response named P50m, however, there have been only
      few studies with controversial findings. In the present study, auditory evoked
      responses to the unilateral tone stimuli were measured in 36 right-handed normal
      subjects, using a helmet-shaped whole head magnetoencephalography system. In a
      total of 72 hemispheres of 36 subjects, P50m dipolar patterns were observed
      statistically (p > 0.02) frequently in the contralateral hemispheres (63.9%)
      compared to the ipsilateral hemispheres (43.0%). N100m dipolar patterns were
      observed over both left and right hemispheres either by left or right ear
      stimuli. Peak latency of the P50m was statistically (p < 0.02) shorter in the
      contralateral hemisphere (45.0 +/- 8.5ms, mean +/- s.d.) compared to the
      ipsilateral hemisphere (54.4 +/- 11.5ms). Peak latency of the N100m was also
      statistically (p < 0.001) shorter in the contralateral hemisphere. Moreover, when
      compared between contralateral responses, the left-ear stimulated right
      hemispheric response (84.6 +/- 8.4) was statistically (p < 0.05) faster than the
      right-ear stimulated left-hemispheric response (89.3 +/- 10.2ms). These results
      indicate that contralateral auditory cortex dominates the ipsilateral cortex at
      the middle as well as the long latency components. Moreover, at least for pure
      tone stimuli, right hemispheric dominance was indicated for the N100m responses.
      The whole-head MEG system is suitable to analyze small but significant
      interhemispheric difference of auditory function.

PMID- 7577147
TI  - The role of nurses in restructuring the Japanese health system for the benefit of
      consumers.

PMID- 7577146
TI  - [Primary intracranial malignant epidermoid--case report].
AB  - Intracranial malignant epidermoid is uncommon. We report a case of a 74-year-old
      woman with a primary intracranial malignant epidermoid in the parapontine region.
      The tumor was visualized as two components (a low-density benign prepontine
      lesion and a malignant enhanced cerebellopontine angle lesion) on CT scan. On
      MRI, the benign portion demonstrated low-signal intensity on T1 weighted images
      and markedly increased heterogeneous signal intensity on T2 weighted images,
      while the malignant portion showed iso-signal intensity on T1 weighted images
      that was markedly enhanced and heterogeneous signal intensity on T2 weighted
      images. Lack of contrast enhancement is a typical finding in benign epidermoid,
      although rim enhancement has been described in a few cases. In our patient, the
      contrast enhancement on CT scan in the otherwise typical epidermoid cyst
      suggested malignant degeneration. Using MR imaging, we could distinguish
      malignant epidermoid from benign epidermoid cyst more precisely.

PMID- 7577148
TI  - Almost misdiagnosed: utilization of Romhilt-Estes electrocardiographic criteria
      for left ventricular hypertrophy.
AB  - The diagnosis of hypertension is based on explicit guidelines presented by the
      Joint National Committee on Hypertension, but the methodology one uses to obtain
      the necessary data is up to the individual practitioner. The following case study
      demonstrates the necessity for the use of the most accurate and precise equipment
      and criteria to ensure a correct diagnosis of hypertension.

PMID- 7577149
TI  - Over-the-counter medication recommendation practices among nurse practitioners in
      Connecticut.

PMID- 7577150
TI  - Secondary amenorrhea.

PMID- 7577151
TI  - Expression of prostaglandin E receptor subtypes in bone: expression of EP2 in
      bone development.
AB  - Prostaglandin (PG) E2 displays physiological and pharmacological action in
      various tissues including bone. It increases intracellular Ca, and stimulates or
      inhibits cAMP production through the PGE receptor subtypes EP1, EP2, and EP3,
      respectively. These receptor subtypes have been recently cloned. In the present
      study, we investigate the expression of these receptor subtypes in bone tissue.
      RT-PCR revealed that EP1, EP2, and EP3 were expressed in rat calvariae and that
      osteoblastic cells (MC3T3-E1) expressed EP1 and EP2. In situ hybridization
      analysis using cryosection of neonatal calvariae revealed that EP2 was expressed
      by osteoblasts and cells not in contact with bone, probably including
      preosteoblasts. EP2 expression was observed at an early stage in calvarial
      development, at 14 days prenatal. EP2 expression was also observed at day 3 in
      rat bone marrow cell culture in which bone-like mineralized nodules are formed at
      day 8. It has been established that PGE2 response accompanying cAMP production is
      one of the characteristics of osteoblasts. The present results indicate that this
      phenotype appears at an early stage of osteoblastic differentiation and bone
      development.

PMID- 7577152
TI  - Origin of a negative calcium response element in an ALU-repeat: implications for
      regulation of gene expression by extracellular calcium.
AB  - The negative calcium response element type 2 (nCARE) is a regulatory DNA sequence
      consisting of a palindromic core sequence and several upstream T residues, which
      was originally described in the 5' flank of the human PTH gene. The nCARE
      functions in an orientation-specific manner to inhibit PTH transcription in
      response to raised extracellular calcium levels. Here we report that the PTH
      nCARE lies within a hitherto unrecognized ALU-like element situated approximately
      3.6 kB upstream of the human PTH gene transcriptional start site. Since ALU
      elements are repetitive DNA sequences, which are widely distributed throughout
      the human genome, we hypothesized that other nCARE elements might also exist. A
      search of the GenBank/EMBL databases with the nCARE core sequence confirmed this
      to be the case showing the presence of 111 copies of the nCARE in human/primate
      sequences. Analysis of the 7SL RNA sequence from which ALU elements derive also
      showed the presence of an nCARE "core" sequence immediately upstream of the poly
      A+ tail. These data suggest that the nCARE is derived from retrotransposition of
      7SL RNA and forms an integral part of many ALU elements; reverse transcription of
      the poly-A+ tail of 7SL RNA adds T residues, which on retrotransposition into
      genomic DNA with the core sequence, forms an ALU element containing a functional
      nCARE. Some of the genes associated with nCARE elements express products which
      are affected by extracellular calcium concentrations and work is in progress to
      determine the functional effects of nCARE at these sites.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7577153
TI  - Carboxylation of osteocalcin in post-menopausal osteoporotic women following
      vitamin K and D supplementation.
AB  - The effect of vitamin supplements on bone metabolism indices in patients with
      osteoporosis has received scant attention in the literature. Over a 2-week
      period, vitamin supplements of K and K+D were given to 20 post-menopausal
      osteoporotic women with previous Colles fractures. Osteoporosis was confirmed by
      bone mass measurements that demonstrated that broadband ultrasound attenuation
      (os calcis) was almost as discriminatory as dual energy X-ray absorptiometry
      (spine and hip) in Colles fracture patients compared with matched controls.
      Vitamin K corrected the carboxylation defect in osteocalcin and while less marked
      4 weeks later, the improvement was still detectable. The result after K+D was
      similar. The level of carboxylation became the same as in premenopausal women.
      Total osteocalcin level (bound) osteocalcin. While there was vitamin K
      correctable undercarboxylation of osteocalcin, simultaneously there was no
      evidence of undercarboxylation of prothrombin.

PMID- 7577154
TI  - Progesterone antagonist RU 486 has bone-sparing effects in ovariectomized rats.
AB  - We demonstrated previously that progesterone prevents ovariectomy-induced bone
      loss. RU 486 is a synthetic steroid with antiprogesterone activities in
      reproductive tissue. We used 12-week-old rats to evaluate effects of RU 486 in
      sham-operated rats and to compare medroxyprogesterone (MPA), RU 486, and
      medroxyprogesterone plus RU 486 combined treatment in ovariectomized rats.
      Ovariectomized rats were treated with MPA (60 mg/kg intramuscularly), RU 486 (10
      mg/kg/day subcutaneously every 4 days), both, or vehicle. Sham-operated rats were
      treated with similar doses of RU 486 or vehicle. After 4 weeks of treatment the
      rats were sacrificed and bone histomorphometry was performed on proximal tibial
      metaphysis. Trabecular bone volume was lower (33.9 +/- 1.5% vs. 46.3 +/- 1.4%)
      and bone turnover was higher in ovariectomized than in sham-operated rats. The
      fraction of trabecular bone in OVX rats treated with MPA, RU 486, or both were
      41.6 +/- 2.5%, 44.8 +/- 2.8%, and 38.4 +/- 1.4%, respectively.
      Medroxyprogesterone treatment tended to preserve bone mass by inhibiting the
      increased resorption indices while maintaining higher formation rates seen in
      ovariectomized rats. The effects of RU 486 were similar to those of
      medroxyprogesterone, suggesting an agonist-like effect. Medroxyprogesterone
      effects were attenuated when it was combined with RU 486, suggesting that RU 486
      acted as a partial antagonist in the presence of exogenous progesterone. Bone
      parameters were less affected in sham-operated RU 486-treated rats, and there was
      no significant change in bone volume (43.2 +/- 1.7%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577155
TI  - Trabecular microstructure in the medial condyle of the proximal tibia of patients
      with knee osteoarthritis.
AB  - The microstructural characteristics of osteoarthritic subchondral bone in the
      medial tibial condyle are clearly different from normal age-matched bone.
      Subchondral sclerosis in osteoarthritis indicates not only an increase in bone
      volume fraction but also alteration in other microstructural characteristics.
      Eleven medial tibial condyles were collected from ten subjects during
      arthroplastic surgery for knee oseoarthritis. They were compared to four medial
      tibial condyles from four age-matched controls with no history of any bone or
      joint disorder. Six sections from anterior to posterior and three levels from
      proximal to distal were evaluated in each medial condyle. Five histomorphometric
      parameters were measured: bone volume fraction (BVf), trabecular thickness
      (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.S), and trabecular
      connectivity (Tb.C). In general, the osteoarthritic subchondral bone had a higher
      bone volume fraction than control bone but the microstructure was characterized
      by fewer, widely spaced, thicker than normal trabeculae. There were also highly
      localized regional differences by depth from the articular surface and from
      anterior to posterior across the medial condyle. These variations in OA
      subchondral bone microstructure may significantly affect biomechanical competence
      of bone in a way not predictable by bone volume fraction measurements alone.

PMID- 7577157
TI  - Generation of multinucleated osteoclast-like cells from canine bone marrow:
      effects of canine distemper virus.
AB  - Recent evidence has implicated canine distemper virus (CDV) as a possible
      aetiologic agent in Paget's disease of bone and the canine bone disorder,
      metaphyseal osteopathy. We have therefore examined the effects of CDV on the
      formation of multinucleated osteoclast-like cells in cultures of canine bone
      marrow mononuclear cells. Marrow cells from a distemper-infected dog and from
      five uninfected dogs were cultured in the presence of 1 alpha, 25-(OH)2 vitamin
      D3 and the number of tartrate resistant acid phosphatase positive multinucleated
      cells (MNCs) was determined. The presence of calcitonin (CT) receptors was
      confirmed by autoradiography with 125I-labeled human CT. Cultures from the
      distemper-infected dog contained a higher level of MNCs than those from the
      normal dogs. The in vitro addition of CDV to the cultures from all the dogs
      produced a dose-dependent increase in the number of MNCs, and an increase in size
      of these cells in the cultures from the infected dog. Cells infected with CDV
      were hyperresponsive to 1 alpha,25-(OH)2 vitamin D3. The presence of the virus in
      the relevant samples was confirmed using molecular techniques. In situ
      hybridization studies also revealed a significant increase in the level of
      infection following in vitro addition of the virus to the culture from the
      distemper-infected dog, suggesting that further infection had taken place.
      Resorption pits were formed on bone slices, although the number of pits was not
      significantly altered by viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577156
TI  - Calbindin-D28K and -D9K and 1,25(OH)2 vitamin D3 receptor immunolocalization and
      mineralization induction in long-term primary cultures of rat epiphyseal
      chondrocytes.
AB  - Rat epiphyseal plat chondrocytes were grown on glass slides, as nonadhering
      monolayer cultures for up to 6 weeks. Chondrocyte growth, differentiation and
      maturation, matrix formation and mineralization, and the temporospatial
      distribution of the vitamin D-dependent calcium-binding proteins, calbindin-D9K
      and -D28K, and the 1,25(OH)2D3 receptor (VDR), were all monitored. Chondrocytes
      became confluent in 2.5 weeks, differentiated to acquire a chondrocyte
      (polygonal) morphology, produced extracellular matrix, and finally formed a true
      monolayer mineralizing cartilaginous tissue, with all the stages of chondrocyte
      development within a single culture. beta-Glycerophosphate promoted initial
      matrix mineralization in 4 weeks and accelerated cell differentiation. High
      nominal calcium and ascorbic acid were needed for abundant matrix formation. VDR
      occurred at all differentiation stages, in the nuclei and nucleoli and in the
      cytoplasm. Calbindin-D28K and -D9K were not coexpressed. Calbindin-D28K was found
      in prechondroblasts, chondroblasts, and in newly differentiated chondrocytes. It
      was cytoplasmic in prechondroblasts and subsequently also in the perinuclear
      region and in nuclei, suggesting migration to the nuclear chromatin. Calbindin
      D28K was nuclear only in newly differentiated chondrocytes in vitro and was not
      found in mature chondrocytes. In contrast, calbindin-D9K was present in the
      cytoplasm of mature and hypertrophic chondrocytes only. It was first in the cell
      body and eventually migrated within and to the far end of long cell processes
      with a decreasing cytoplasmic concentration showed by decreased immunostaining
      intensity, and ultimately hypertrophy of chondrocytes in culture. These in vitro
      patterns of calbindins-D and VDR accurately reflect their in vivo distributions.
      The genomic action of vitamin D, in vitro, resulted in the synthesis of nuclear
      VDR and calbindins-D.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577159
TI  - Changes in urinary deoxypyridinoline level and vertebral bone mass in the
      development of adjuvant-induced arthritis in rats.
AB  - This study was designed to determine the effect of bone resorption on the
      development of generalized osteopenia in adjuvant-induced arthritic rats. Thirty
      of a total of sixty male SD rats, 6 weeks of age, were injected with killed
      mycobacterium butyricum suspended in mineral oil into the right hind paw and
      assigned to six groups of 5 animals each. The other thirty animals served as the
      age-matched noninjected controls. Animals were sacrificed at 4, 7, 10, 14, 21,
      and 28 days post-injection after measuring the bilateral hind-paw volumes. Twenty
      four-hour urinary samples were obtained before sacrifice and the levels of
      deoxypyridinoline (D-Pyr) and creatinine (CR) were measured. Plasma intact
      osteocalcin levels were measured by a sandwich enzyme immunoassay at the start,
      14 and 28 days after injection. Bone mineral measurement and histomorphometrical
      analyses were performed on specimens of the third lumbar vertebral body. On the
      seventh day after injection, arthritic rats showed significant decreases in the
      values of bone mineral content (BMC) and density (BMD) when compared to controls.
      Urinary D-Pyr/Cr ratios, however, did not increase on the seventh day, showing a
      significant increase on the tenth day after injection. The serum osteocalcin
      level was significantly reduced on the fourteenth day. The trabecular bone volume
      (BV/TV) in the arthritic rats showed a significant decrease from the seventh day.
      The trabecular thickness (Tb.Th) value significantly decreased on the seventh day
      after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577158
TI  - Cytokine production by calvariae of osteopetrotic mice.
AB  - In the osteopetrotic op/op mouse, the absence of macrophage colony-stimulating
      factor (M-CSF) prevents the growth of macrophages and osteoclasts and,
      consequently, bone resorption. In the present study, we investigated whether this
      deficiency in M-CSF production alters the production of cytokines in op/op bones.
      Calvariae of phenotypically normal (+/?) and op/op mice were stimulated in vitro
      with lipopolysaccharide or Pasteurella multocida toxin to produce cytokines.
      Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) synthesis was the same both in calvaria from osteopetrotic and
      phenotypically normal animals. However, the production of granulocyte colony
      stimulating factor (G-CSF), interleukin-6 (IL-6), and tumor necrosis factor-alpha
      (TNF alpha) was lower in calvaria from op/op animals than was the case in +/?
      calvaria. Thus, the lack of biologically active M-CSF causes defects which are
      not compensated by cells independent of M-CSF.

PMID- 7577161
TI  - Radiographic absorptiometry of the phalanges in healthy children and in girls
      with Turner syndrome.
AB  - Although bone mineral status in children has been measured with various
      techniques, information about development of the actual bone mass density during
      childhood and adolescent growth is scarce. Our modified radiographic
      absorptiometry (RA) determines bone mass density (BMaD) three dimensionally at
      the diaphyseal and metaphyseal site of the middle phalanx of the left second
      digit, representing predominantly cortical (50% site) and trabecular bone
      compartments (25% site), respectively. The objectives of this study were to
      establish reference curves with 95% prediction intervals of BMaD in relation to
      bone age (BA) during childhood and adolescence (N = 303) determined by RA. The
      specific effects of female puberty on BMaD were studied comparing the values of
      110 untreated girls with Turner syndrome (TS) with those of the female reference
      group. For either sex, a piecewise linear model with one inflection point (IP)
      was postulated for the relationship of both the 25% and 50% site with BA. The IPs
      appeared at exactly the same BA (11.5 "years") for both the 25% and 50% site in
      boys and for the 25% site in girls. However, in girls the 50% site IP appeared
      0.25 "years" later. All BMaD values to the left of the IPs showed little increase
      with age. In contrast, the slopes to the right of the IPs showed in both genders
      regression coefficients of approximately 0.05 for the 25% site. For the 50% site,
      the regression coefficient in girls was markedly higher (0.075) than in boys
      (0.058), resulting only in girls in a significant difference between the 25% and
      the 50% site to the right of the IP (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577160
TI  - Effects of experimental conditions on the release of 45calcium from prelabeled
      fetal mouse long bones.
AB  - Embryonic/neonatal bones in culture are commonly used for the study of
      osteoclastic resorption in vitro. For this purpose, the release of 45calcium
      (45Ca) from prelabeled bones is measured as an index of resorption. We studied
      45Ca release from two types of long bone explants after different preparation
      methods: 17-day-old fetal mouse radii/ulnae with and without cartilage ends
      (intact radii/ulnae and shafts, respectively), and intact 18-day old
      metacarpals/metatarsals. In addition, we examined the effect of different culture
      conditions, such as cultures performed under the surface of the medium or at the
      interphase of medium and air, on 45Ca release and histology. When intact
      radii/ulnae were cultured under the surface of the medium, there was always a
      significant amount (10%) of net basal 45Ca release (corrected for physicochemical
      exchange) that was not due to osteoclastic resorption, as it could not be
      suppressed by inhibitors of resorption even at high concentrations. Moreover,
      histologically TRAcP-positive cells were almost absent after culture and the bone
      marrow/stromal cells in the center of the bone appeared necrotic, possibly due to
      a lack of oxygen. Under these culture conditions, osteoclasts could survive in
      shafts as well as in PTH-stimulated intact radii/ulnae, but a constant amount of
      10% 45Ca, not due to resorption, was still released in the medium. When these
      explants were cultured at the interphase of medium and air, basal and stimulated
      45Ca release originated from osteoclastic resorption. In contrast, in 18-day-old
      fetal mouse metacarpals/metatarsals, the experimental conditions applied did not
      affect 45Ca release, which was always due to resorption of the explants by
      osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577162
TI  - Diurnal rhythm of prostanoid secretion from bone/marrow organ in the rat.
AB  - The secretion of prostanoids from an adult diaphysial rat bone organ was assessed
      throughout a 24 h period at 4 h intervals as well as the 24 h activities of bone
      alkaline phosphatase isoenzyme and serum corticosterone levels. Femurs were
      removed from 16 rats at each interval and incubated in the absence or presence of
      indomethacin (100 micrograms). The levels of prostaglandin E2 (PGE2)
      prostaglandin F2 alpha (PGF2 alpha), and the stable metabolites of thromboxane
      and prostacyclin, thromboxane B2 (TxB2), and 6-keto prostaglandin F1 alpha (6
      keto PGF1 alpha) were measured by radioimmunoassay (RIA). The patterns for each
      of the variables was subjected to cosinor analysis for predetermined various
      periods. The chronograms obtained indicated that PGF2 alpha, PGE2, and TxB2
      showed 24 h rhythms with computed peak hour acrophases at 1700, 1800, and 2200 h,
      respectively, and prostacyclin demonstrated a 19 h rhythm with a peak secretion
      at 1100 h. Corticosterone levels and bone alkaline phosphatase isoenzyme activity
      in the serum were at peak at 1630 and 2200 h, and at nadir at 0500 and 1000 h,
      respectively, both exhibiting 24 h rhythms similar to those of PGF2 alpha, PGE2,
      and TxB2. Bone alkaline phosphatase isoenzyme activity in the femurs' incubation
      media showed a 12 h diurnal rhythm with peaks at 1230 and 2330 h and nadirs at
      0600 and 2330 h (p < 0.01). In summary, this study demonstrated for the first
      time a 24 h rhythm of prostanoid secretion from diaphysial bone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577163
TI  - The anisotropy of osteonal bone and its ultrastructural implications.
AB  - The anisotropic elastic symmetry of osteonal bone reflects the ultrastructural
      organization of collagen fibrils and mineral crystals within the osteons as well
      as the lamellar microstructure. Until recently, reported values for bone's
      anisotropic elastic properties were limited in their interpretation by poor
      precision and resolution of measurement techniques. Here, we report measurements
      of bone anisotropy using high precision acoustic microscopy. The elastic
      properties of canine femoral bone specimens, taken from 23 femora, were measured
      at 10 degrees increments from the long axis of the bone. Half of the bone
      specimens subsequently were demineralized in EDTA solution, the other half were
      decollagenized in sodium hypochlorite solution, and the acoustic measurements
      were repeated. We found the elastic symmetry of osteonal bone deviates
      significantly from orthotropic theory supporting the hypothesis that the lamellar
      microstructure forms a "rotated plywood" (Weiner and Traub, FASEB J 6:879-885;
      1992). The principal orientation of bone mineral was along the long axis of the
      bone, while bone collagen appeared to be aligned at a 30 degrees angle to the
      long axis. The misalignment between the mineral and the collagen suggests that
      (1) a substantial percentage of the mineral is extrafibrillar, and (2) the
      alignment of extrafibrillar mineral is governed by external influences, e.g.,
      mechanical stresses.

PMID- 7577165
TI  - Dental sponsorship.

PMID- 7577164
TI  - Changes in the carboxyl-terminal propeptide of type I procollagen and other
      markers of bone formation upon five days of bed rest.
AB  - This study was performed in order to investigate the influence of skeletal
      unloading on the serum concentration of the carboxyl-terminal propeptide of type
      I procollagen (sPICP) and other markers of bone formation. Blood samples were
      taken every third hour from nine healthy premenopausal women (22-29 years) in two
      24 h studies, before and at the end of five days of bed rest. Furthermore, a set
      of samples were taken 12 h apart after three days of bed rest. We measured sPICP,
      the serum concentration of intact and N-terminal-Mid fragment osteocalcin (sOC),
      and the serum concentration of alkaline phosphatase (sAP). During the five days
      of bed rest a gradual increase in sOC was observed, while sPICP gradually
      decreased. sAP was unchanged. Five days of best rest resulted in the following
      overall changes in the 24 h mean values: sPICP: -14% (p = 0.002); sOC: +9% (p =
      0.009); sAP: -1% (not significant). The circadian patterns did not change
      significantly after bed rest. It is puzzling that the changes in the bone
      formation markers are of different magnitude, and for sPICP and sOC even in
      opposite directions. The increase in sOC may be caused by an increase in OC
      secretion by the osteoblasts or a release of bone-incorporated OC from resorbing
      sites; the accompanying decrease in sPICP may indicate that bone formation is
      actually transiently decreased after short term bed rest.

PMID- 7577166
TI  - MRI update.
AB  - The Management Research Initiative is successfully attracting interest from the
      business and management world in a drive to see dentistry recognised as a key
      area for management research. This issue's MRI update reports on the reception
      the initiative received at this year's British Academy of Management conference,
      and how dental practitioners can assess and improve their strategy planning by
      participating in research to be carried out at the Sheffield Business School.

PMID- 7577168
TI  - Infection control in general dental practice.

PMID- 7577167
TI  - Child dental health survey.

PMID- 7577169
TI  - The provision of orthodontic treatment.

PMID- 7577170
TI  - Dental anaesthesia report.

PMID- 7577171
TI  - Future funding for dentistry.

PMID- 7577172
TI  - Left handed GDPs and dental nurses.

PMID- 7577173
TI  - Toxic effects of materials used in dental restorations.

PMID- 7577174
TI  - Further thoughts on the sugar dust caries.

PMID- 7577176
TI  - Specialist dental training.

PMID- 7577175
TI  - Further thoughts on the sugar dust caries.

PMID- 7577177
TI  - Student debt.

PMID- 7577178
TI  - Issues of latex safety in dentistry.
AB  - The prevalence of reported reactions to natural rubber latex products in both the
      general population and in dental personnel appears to parallel the rise in glove
      wearing by health professionals. This paper reviews the irritant and allergic
      reactions which may be associated with latex products, particularly gloves. The
      aetiology, pathogenesis, diagnosis and management of immediate Type I (IgE
      mediated) responses to latex are described in some detail. The paper provides the
      reader with an insight into factors that may lead to latex allergy and outlines
      measures for handling 'latex sensitised' individuals in the dental surgery.

PMID- 7577179
TI  - The impact of quality control on radiography in general dental practice.
AB  - The aim of this study was to assess the impact of two quality control measures
      upon the quality of periapical radiographs in general dental practices. Five
      general dental practitioners took part in the study. Periapical radiographic
      quality was assessed before and after the introduction of film holders and
      quality control measures for processing. Prior to the introduction of the quality
      control measures, 49% of radiographs were assessed as being 'unacceptable', 49%
      exhibited faults but were 'acceptable' for diagnostic purposes, while only 2% of
      radiographs were 'excellent' being entirely free of faults. After the
      introduction of film holders and processing quality control procedures 39% were
      'unacceptable' (P < 0.05), 56% were 'acceptable' and 5% of radiographs were
      classified as 'excellent'. It is concluded that current recommendations to
      dentists to use film holders and to carry out processing quality control are
      justified in terms of an improvement in the diagnostic quality of radiographs.
      However, improvements in undergraduate and continuing education for all members
      of the dental team, with emphasis on practical 'hands-on' instruction, may
      improve the effectiveness of these recommendations.

PMID- 7577181
TI  - World War II: the Army Dental Corps in the Far East.
AB  - This final part of the series on The Army Dental Corps during the Second World
      War continues with the stories of dental personnel who were captured and
      incarcerated in the prisoner of war camps in the Far East. What is remarkable
      about all of these stories is the evident spirit to survive and determination to
      keep life, which was often hellish, as near to normality as was conceivably
      possible.

PMID- 7577180
TI  - Oral mucosal screening as an integral part of routine dental care.
AB  - The principal aim of this study was to assess the feasibility of conducting a
      systematic examination of the oral mucosa, as an integral part of the routine
      dental check-up and in conditions comparable with those in NHS dental practice. A
      total of 1949 individuals, who were already registered as patients with an
      industrial dental clinic, were invited to attend for an oral screen as part of
      their dental examination. Of these, 1947 patients agreed to participate and were
      also asked to complete a 'habits' questionnaire relating to their tobacco and
      alcohol use. A systematic examination of the oral mucosa was undertaken as part
      of the routine dental inspection and mucosal lesions were recorded as either a
      positive or negative screening result. Lesions included as a positive result were
      those which may be associated with early cancer or precancer. Four patients
      (0.2%) were considered to have a positive screening result and these were
      referred for specialist evaluation. Of these, two had tobacco-related
      leukoplakia, one had oral lichen planus and the other had an early squamous cell
      carcinoma. This study has confirmed that a systematic and thorough examination of
      the oral mucosa can realistically be carried out as part of the routine dental
      inspection in NHS dental practice.

PMID- 7577182
TI  - Evidence based dentistry.
AB  - We live in an age of information, innovation and change. Clinical decision making
      based on good quality evidence should lead to more effective and efficient
      treatments. Each practitioner has a role in assessing this information. This
      paper outlines this role, together with the advantages and problems of
      introducing an evidence based approach to dentistry.

PMID- 7577183
TI  - Continuing professional development.

PMID- 7577184
TI  - Is school screening just a paper exercise?

PMID- 7577185
TI  - Undergraduate dental education: re-inventing the wheel?
AB  - Education for dental students has long been a subject for debate but as this
      article suggests, the arguments often just take us round in a perpetual circle.
      If any valuable progress is to occur, the profession needs to rethink its long
      established opinions on this issue and consider where change is actually
      realised.

PMID- 7577186
TI  - Fluoride dentifrices.

PMID- 7577189
TI  - Maintaining the quality of dental undergraduates for general dental practice: a
      performance management study.
AB  - An investigation and survey explored the effect of the display of dental
      undergraduates clinical performance by a process termed silent monitoring. The
      study measured the effect of silent monitoring on the quality of patients'
      treatment and the frequency of non-attendance at appointments for patients
      arranged by undergraduates. A cross-sectional study also estimated the impact of
      silent monitoring on undergraduates' clinic time use. Both enquiries revealed
      that silent monitoring motivated students. It significantly increased the number
      of patients treated and reduced the non-attendance of appointments. However,
      there was an increase in the incidence of patients informing undergraduates that
      they could not attend appointments. This phenomenon allowed the rescheduling of
      appointments and better use of clinic time. Silent monitoring increased the time
      undergraduates spent preparing for the patients' treatment. it also improved the
      patients punctuality. Evaluation of the procedure by questionnaires showed
      approval of the method, although some undergraduates felt that aspects of their
      assessment were unfair. A survey revealed that other United Kingdom dental
      schools do not use silent monitoring. If they adopted such a method, it could
      have similar positive influences on their undergraduates' management of clinical
      practice and improve the quality for dental practice.

PMID- 7577187
TI  - Inferior dental block.

PMID- 7577188
TI  - Patient decision-making.

PMID- 7577190
TI  - The development of a behavioural science course into the dental curriculum at
      Liverpool Dental School.
AB  - The behavioural science course for the undergraduate dental curriculum at
      Liverpool university Dental School is designed to be integrated into the basic
      science and clinical teaching. The course is taught by a clinical psychologist
      and social anthropologist. The course has an input to each of the 5 years of the
      student's training. This paper presents three examples (community dental visits,
      communication skills training and special symposia) of how the course is being
      developed, illustrating the strengths and some shortcomings requiring further
      development.

PMID- 7577191
TI  - Pilot study of an orthodontic treatment need learning package for general dental
      practitioners.
AB  - This pilot study evaluated an Index of Orthodontic Treatment Need Learning
      Package which was developed for use by general dental practitioners. Fifty-seven
      dentists participated in a randomised controlled trial which involved assessing
      the need for orthodontic treatment among two representative samples of 16 study
      casts. All the dentists assessed the first set of study casts without any aids or
      assistance. During the assessment of the second set of study casts one group of
      dentists used an IOTN Learning Package in the form of a poster, another group
      used an IOTN Learning Package in the form of a booklet, and the remaining group
      acted as a control and did not use any Learning Package. The results reveal that
      compared with the control dentists, the dentists using the IOTN poster and the
      IOTN booklet had, respectively, 1.8 and 2.6 fewer errors when assessing aesthetic
      need and 2.0 and 2.1 fewer errors when assessing dental health need.

PMID- 7577193
TI  - Second year general professional training for dentists: the West Midlands
      regional scheme one year on.
AB  - the West Midlands regional scheme offers new dental graduates the opportunity to
      undertake a 2-year period of general professional training prior to embarking on
      their chosen career pathway. Ideally experience should be gained in primary and
      secondary care. This paper describes the second year of the West Midlands scheme
      introduced a year ago, which combines house officer and general practice
      experience.

PMID- 7577192
TI  - Policies and practices of European dental schools in relation to smoking: the
      place of tobacco education in the undergraduate dental curriculum.
AB  - A postal questionnaire was used to ascertain policies and practices of European
      dental schools in relation to smoking and the teaching of the relationship of
      smoking to the aetiology and primary prevention or oral cancer. A majority of
      responding schools taught the role of smoking in the aetiology of oral cancer. A
      majority expected students to take smoking histories from patients. Half of
      schools taught anti-smoking advice to students and half expected students to
      impart such advice to patients. A majority banned smoking in clinical and non
      clinical teaching facilities and associated public access areas. There is scope
      for considerable improvement in curricula in relation to anti-smoking counselling
      and in the practices of schools in expecting students to act as tobacco
      counsellors.

PMID- 7577194
TI  - VT2--a trainee's point of view.
AB  - A pilot scheme for a second year of vocational training started in January 1994
      in the West Midlands region. The position involved working part time as an
      associate dental surgeon in an approved general dental practice and part time as
      a house officer rotating around the various departments at the Birmingham Dental
      Hospital. Throughout the year there were 15 days termed 'study days' when
      lectures and courses on topics requested by those involved were arranged. At the
      end of the year those involved in the scheme were eligible to take the DGDP
      examination. This paper outlines my own thoughts of the year.

PMID- 7577196
TI  - Introduction to clinical economics: assessment of cancer therapies.
AB  - Recent changes in the health care environment have led to the assessment of the
      costs and benefits of cancer treatment as criteria for the evaluation of new
      cancer therapies. The methodological framework for these assessments is provided
      by the field of clinical economics, a discipline that combines the techniques
      from clinical medicine, economics, epidemiology, and biostatistics. This article
      reviews the concepts of clinical economics and issues related to economic
      analysis of new therapies. This type of information is increasingly important to
      patients, clinicians, and health policy decision makers to help assure patients'
      access to effective cancer therapies.

PMID- 7577195
TI  - Synthesis, analysis and toxicity of three compounds formed during the synthesis
      of iodixanol.
AB  - The origin of 4-acetyl-2-[N-acetyl-3,5-bis(2,3-dihydroxypropylcarbamoyl)- 2,4,6
      triiodoanilinomethyl]-5,7-diiodo-3,4-dihydro-2H-benzo[1,4]ox azine- 6,8
      dicarboxylic acid bis(2,3-dihydroxypropylamide) = N-acetyl cyclized iodixanol, 2
      [N-acetyl-3,5-bis-(2,3-dihydroxypropylcarbamoyl)-2,4,6- triiodoanilinomethyl]-5,7
      diiodo-3,4-dihydro-2H-benzo[1,4]oxazine- 6,8-dicarboxylic acid bis(2,3
      dihydroxypropylamide) = cyclized iodixanol and 5,5'-(N-acetyl-2-hydroxypropane
      1,3-diyldiamino)bis[N,N'-bis(2,3- dihydroxypropyl)-2,4,6-triiodoisophthalamide] =
      deacetyl iodixanol in the manufacturing process of the X-ray contrast agent
      3,3',5,5'-tetrakis(2,3-dihydroxypropylcarbamoyl)-2,2',4,4',6,6'-++ +hexaiodo-
      N,N'-(2-hydroxypropane-1,3-diyl)diacetanilide = iodixanol is discussed and their
      synthesis and purification are described. Their physical and toxicological
      properties, and analytical and spectroscopic data are summarized.

PMID- 7577197
TI  - Special issues that arise in applying techniques of economic analysis to
      evaluation of cancer therapies.
AB  - The papers presented at this conference and reprinted in this monograph provide
      an opportunity to begin the process of establishing a shared language, set of
      goals, and "methods tool chest" for clinical researchers and economists to use in
      approaching the integration of economic analysis into cancer clinical trials. The
      first step in this process should be to recognize that there are several special
      issues that arise in applying the techniques of economic analysis to the
      evaluation of cancer therapies. These issues include the following: 1) The
      clinical course of cancer is complex, 2) clinical research and clinical trials
      are in the mainstream of cancer care, 3) cancer therapy is multidisciplinary, and
      4) "best supportive care" is a rarely studied alternative.

PMID- 7577198
TI  - Whole abdominal radiotherapy versus combination chemotherapy with doxorubicin and
      cisplatin in advanced endometrial carcinoma (phase III): Gynecologic Oncology
      Group Study No. 122.
AB  - Although localized endometrial cancer is effectively treated with surgery and
      radiation therapy, the treatment of advanced disease remains problematic. With
      increasing utilization of primary surgical staging and therapy, the early
      identification of patients with tumor spread beyond the uterus is becoming
      routine. The impact of adjuvant radiotherapy and/or chemotherapy in these
      patients remains to be demonstrated. In several institutions, whole abdominal
      radiation therapy has been used with some success as adjuvant treatment in
      selected patients with advanced disease. The Gynecologic Oncology Group (GOG) has
      completed a phase II trial of the whole abdominal radiotherapy in this patient
      population. Although data analysis is not complete, the regimen employed appears
      to be tolerable and shows some evidence of efficacy. In previous GOG trials,
      cisplatin and doxorubicin have shown single-agent activity in patients with
      measurable, advanced endometrial cancer. Subsequently, the response rate with the
      combination of cisplatin and doxorubicin was found to be superior to that with
      doxorubicin alone. Because approximately 30%-50% of patients with extrauterine
      disease have systemic failure, the evaluation of combination chemotherapy with
      doxorubicin and cisplatin in the adjuvant setting seemed warranted. The current
      ongoing prospective, randomized trial (GOG No. 122) compares the survival and the
      progression-free interval and treatment failure patterns in patients with
      endometrial carcinoma of stage III or IV with up to 2 cm of residual disease when
      treated with either whole abdominal radiotherapy or a combination of doxorubicin
      and cisplatin. The incidence and type of acute and late adverse events observed
      with the two treatment regimens were determined and compared.

PMID- 7577199
TI  - Economic considerations in comparing whole abdominal radiotherapy with
      combination doxorubicin-cisplatin chemotherapy in advanced endometrial carcinoma:
      how much economic data should be collected?
AB  - The key features of this study from the perspective of designing an economic
      analysis are that the resources consumed and the expected toxic effects are
      likely to be quite different in the two study arms, median survival will be
      measured in years, and the initial treatment assignment may affect the clinical
      course and resource consumption of the terminal phases of illness. Collecting
      complete data on all the costs associated with treatment, short-term toxic
      effects, long-term toxic effects, and treatment of recurrent disease as well as
      tracking the complex clinical course of patients over many years of follow-up
      would be an enormous undertaking. However, "phase II" or historical data on the
      costs and outcomes of care associated with each of these two treatment regimens
      would allow for a more tailored approach. But perhaps the first question that
      should be answered in designing an economic analysis to accompany a clinical
      trial is whether the resulting data are likely to be important. This study does
      not fulfill one of the main criteria for judging the appropriateness of including
      an economic analysis--large resource consequences. Fewer than 6000 cases of stage
      III or IV endometrial cancer occur annually in the United States, of which only a
      portion would be appropriate for the alternative treatment strategies evaluated
      in this protocol. Therefore, although the clinical question posed by this
      protocol is appropriate and important, the aggregate economic consequences of
      choosing one treatment approach over the other may not be of sufficient magnitude
      to justify the investment in a prospective economic analysis conducted alongside
      the clinical trial.

PMID- 7577200
TI  - Relationship between dose schedule and charges for treatment on National Wilms'
      Tumor Study-4. A report from the National Wilms' Tumor Study Group.
AB  - National Wilms' Tumor Study-4 was designed to evaluate the efficacy, toxicity,
      and cost of administration of different regimens for the treatment of Wilms'
      tumor. The charges for treatment with dactinomycin and doxorubicin administered
      by two different schedules were calculated using current charges in Buffalo, N.Y.
      An annual savings of approximately $779,259 could be achieved by the use of the
      short, pulse-intensive (i.e., single-dose) treatment regimens for all children
      with Wilms' tumor of stages I-IV/favorable histology. The pulse-intensive
      administration schedule for the treatment of children with Wilms' tumor permits
      administration of chemotherapy at a substantially lower total treatment cost.

PMID- 7577201
TI  - National Wilms' Tumor Study: economic perspective.
AB  - The National Wilms' Tumor Study poses a question of an essentially economic
      nature: Can the socioeconomic impact of therapy for Wilms' tumor on the patient's
      family and society be lessened without compromising the efficacy of therapy? But
      the only proposed measure of socioeconomic impact appears to be the extent of
      hospitalization. From an economic perspective, more information is ideally needed
      from the trial to establish the magnitude of any difference in effectiveness and
      the magnitude of the difference in costs, so that any trade-off between the two
      can be assessed. In practice, the extent of the economic data needed at the end
      of the study will depend on the clinical outcome results and, hence, the nature
      of the trade-off that will have to be made. If the less extensive treatment is
      found to be ineffective, economic issues will not come into play. Similarly, if
      the less extensive treatment is clearly superior in every clinical aspect, the
      argument for it will probably be persuasive. The interesting situation of a trade
      off arises if the less extensive treatment offers clear socioeconomic advantages
      but has some small clinical disadvantage. In that case, the extent and nature of
      an array of socioeconomic factors will need to have been measured, not just
      presumed. There are, of course, many problems associated with collecting and
      analyzing more comprehensive socioeconomic data in a long trial. This article
      considers a number of these problems and focuses on six important issues in
      designing the necessary economic components of future trials.

PMID- 7577202
TI  - Design and conduct of a double-blind, placebo-controlled trial of daunorubicin
      and cytarabine with or without granulocyte colony-stimulating factor in elderly
      patients with acute myeloid leukemia: a Southwest Oncology Group study.
AB  - From the public health standpoint, acute myeloid leukemia (AML) is an important
      problem for both young and older adults. AML is the leading cause of cancer death
      in men aged 15-34 years and the second leading cause of cancer death in women in
      this age group. This clearly has an impact on loss of life in the productive
      years. But in terms of the population most affected and of the biology of the
      disease, the impact is even greater for the elderly patient. Age has been
      established in many AML treatment trials as a poor prognosis factor. Although
      ther is no consensus as to what age defines an elderly AML patient, those older
      than 45 years have a lower complete remission (CR) rate than those who are
      younger. In patients younger than 50 years, the average CR rate is 60%-75%; in
      contrast, in patients older than 70 years, the CR rate is 35%-40%. Long-term
      disease-free survival ranges from 25% to 50% in adult AML, depending on the post
      remission therapy used and the age of the patient. In November 1991, the
      Southwest Oncology Group began a study to address the problems of treating AML in
      the elderly. Many previous treatment trials of AML have included elderly patients
      as a subgroup of the study analysis, with a larger proportion of young patients.
      This trial was designed to test the hypothesis that a myeloid growth factor used
      as supportive care could improve the outcomes in elderly patients with
      AML.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577203
TI  - Double-blind, placebo-controlled trial of daunorubicin and cytarabine with or
      without recombinant human granulocyte colony-stimulating factor in elderly
      patients with acute myeloid leukemia: economic evaluation with attention to
      inpatient and outpatient resource utilization.

PMID- 7577206
TI  - Proposed phase III trial comparing laparoscopic-assisted colectomy versus open
      colectomy for colon cancer.
AB  - Despite many important medical advances, surgery remains the primary treatment
      modality for most of the 109,000 individuals who are newly diagnosed with colon
      cancer each year. Surgery not only provides extirpation of the primary tumor that
      relieves symptoms and prevents complications but also provides important staging
      information. Although oncologic results from open colectomy are well established,
      these traditional resective and staging techniques are challenged by the
      introduction of minimal-access surgery. Laparoscopic cholecystectomy, which
      shortens postoperative recovery and decreases disabilities and cost, has become
      the preferred surgical approach to cholelithiasis. Many propose that minimal
      access surgery of the colon may offer similar advantages. Laparoscopic-assisted
      segmental resections of the colon can be performed using laparoscopic techniques
      to ligate vasculature and mobilize and exteriorize bowel and extracorporal
      techniques to resect and anastomose bowel. Collective preliminary data from a
      consortium of experienced laparoscopic surgeons support that laparoscopic
      assisted colectomy is safe, feasible, and reduces recovery times and
      disabilities. Since differences between laparoscopic-assisted and open colectomy
      have not been rigorously tested, and concern has been raised regarding the
      adequacy of this technique for staging and treating colon cancer, a prospective
      randomized multi-institutional trial is proposed. The primary aim of such a trial
      will be to test the hypothesis that disease-free survival and overall survival
      are equivalent, regardless of whether patients receive laparoscopic-assisted or
      open colectomy. The secondary aim of the trial will be to determine the safety of
      of laparoscopic-assisted colectomy compared with open colectomy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577205
TI  - Economic evaluation of high-dose chemotherapy and bone marrow transplantation for
      patients with breast cancer of stage II or IIIA with more than 10 positive lymph
      nodes at surgical excision.
AB  - Several issues related to the design of a multi-year study of the outcome of high
      dose chemotherapy with bone marrow transplant for patients with metastatic breast
      cancer have been discussed. Important considerations include an understanding of
      the types of data that would be collected through the study period, an assessment
      of treatment benefits and complications, an understanding of the valuation of
      differences in resource consumption across treatment arms, and an informed
      definition of the study population to include in the economic assessment. The
      resulting analysis will help patients and policy makers better understand the
      impact of aggressive treatment options for breast cancer patients.

PMID- 7577204
TI  - Randomized, comparative study of high-dose (with autologous bone marrow support)
      versus low-dose cyclophosphamide, cisplatin, and carmustine as consolidation to
      adjuvant cyclophosphamide, doxorubicin, and fluorouracil for patients with
      operable stage II or III breast cancer involving 10 or more axillary lymph nodes
      (CALGB Protocol 9082). Cancer and Leukemia Group B.
AB  - The prognosis for patients with primary breast cancer involving multiple axillary
      lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years
      from diagnosis despite surgery, conventional-dose chemotherapy, and radiation
      therapy. In nonrandomized studies, the use of high-dose chemotherapy as
      consolidation therapy after standard-dose induction chemotherapy has resulted in
      an apparent improvement in disease-free survival rates to over 70%. These results
      have prompted the National Cancer Institute to sponsor large-scale, multicenter,
      randomized comparative trials of this strategy. This Intergroup Study (Cancer and
      Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer
      Institute of Canada MA13) compares two treatment strategies in women with primary
      breast cancer involving 10 or more axillary lymph nodes. Arms A and B are
      identical in the use of four cycles of conventional therapy with cyclophosphamide
      and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only
      difference between the two arms is the dose intensity of the cyclophosphamide,
      cisplatin, and carmustine given following conventional adjuvant treatment. Arm A
      dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor
      support and frequently requires a prolonged hospital stay with high resource
      utilization. Arm B, with its less dose-intensive therapy, requires considerably
      less support to apply the treatment. Because of the high cost of this therapy and
      the requirement for technology-intensive support, there has been considerable
      interest in economic outcome assessments.

PMID- 7577207
TI  - Clinical and economic assessment of new surgical technologies.

PMID- 7577208
TI  - Phase III trial (E5592) comparing cisplatin plus etoposide with cisplatin plus
      paclitaxel at two dose levels for treatment of advanced non-small-cell lung
      cancer. Eastern Cooperative Oncology Group.
AB  - Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related
      death in the United States. Only about 30% of patients present with surgically
      resectable (and thus curable) disease. Because existing chemotherapeutic regimens
      are never curative in advanced NSCLC and because the median survival time is only
      modestly increased, the Eastern Cooperative Oncology Group (ECOG) has
      concentrated on a broad phase II testing program designed to identify new agents
      with activity against the disease. Of the more than one dozen drugs that have
      been thus evaluated during the past 10 years, only paclitaxel (Taxol) has been
      shown to result in an objective response rate of more than 20%. To determine if
      the paclitaxel-containing regimen can increase survival, ECOG has, therefore,
      embarked on a phase III trial (E5592) in which patients with stage IV NSCLC are
      randomly assigned to receive either cisplatin plus etoposide (the current
      standard chemotherapy) or cisplatin plus paclitaxel. The trial design should also
      help to determine the appropriate dose of paclitaxel in this clinical setting.

PMID- 7577209
TI  - Potential evaluation of the incremental cost-effectiveness of paclitaxel in
      advanced non-small-cell lung cancer (Eastern Cooperative Oncology Group 5592).

PMID- 7577211
TI  - Prostate Cancer Intervention Versus Observation Trial: economic analysis in study
      design and conditions of uncertainty.
AB  - The Prostate Cancer Intervention Versus Observation Trial (PIVOT) compares
      radical prostatectomy with palliative expectant management of patients with
      clinically localized prostate disease. As with all clinical trials, several of
      the assumptions underlying PIVOT are characterized by uncertainty. Economic
      analysis has the potential to clarify some of these important issues, thereby
      guiding study design and interpretation and enhancing the clinical usefulness of
      the findings. One important uncertainty about the trial relates to the true
      clinical state of potentially eligible patients. While clinical examination is an
      insensitive method by which to stage prostate cancer, several diagnostic tests,
      such as bone scanning and magnetic resonance imaging with rectal coil, are more
      accurate but more expensive. Another issue is whether to start the trial with the
      screening of patients or at the time of prostate cancer diagnosis. Economic
      analysis can assess these trade-offs between study cost and validity. A second
      potential role for health economics is in dealing with the considerable
      uncertainty surrounding the study's findings and conclusions and their
      interpretation. While the stated primary outcome of the trial is survival, a
      multidimensional outcome (particularly one that incorporates factors of survival,
      quality of life, and cost) is likely to be more clinically relevant in the
      prostate cancer population, given the only modest improvements in survival
      hypothesized for radical prostatectomy. To develop such a measure, quantitative
      assessment of patient preferences is required, in addition to the measures
      currently included in the study. Assessment of costs of care are important, given
      the large and growing size of the study's target population.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7577210
TI  - Prostate Intervention Versus Observation Trial (PIVOT): a randomized trial
      comparing radical prostatectomy with palliative expectant management for
      treatment of clinically localized prostate cancer. PIVOT Planning Committee.

PMID- 7577212
TI  - Long-term results of intertrochanteric varus osteotomy for arthrosis of the
      dysplastic hip (over 10 years' follow-up).
AB  - We performed a retrospective clinical and radiographic review of the long-term
      results of 64 hips in 53 patients who underwent intertrochanteric varus osteotomy
      for arthrosis of the hip at the pre- or early stage with acetabular dysplasia.
      Their average age at operation was 26 years. The average duration of follow-up
      was 18 years and 10 months. The mean Harris hip score was 77 +/- 9 points pre
      operatively, and improved significantly to 84 +/- 13 points at the final follow
      up. The acetabular coverage influenced the final outcome, and the postoperative
      prognosis was predictable from the acetabular head index (AHI) on a pre
      operatively done hip maximum abduction radiograph (abd XP). We conclude that
      varus osteotomy for a dysplastic hip should be considered when the acetabular
      coverage is sufficient, and that a good prognosis can be expected when AHI on abd
      XP is greater than 60%.

PMID- 7577214
TI  - Autoarthroplasty of knee cartilage defects by osteoperiosteal grafts.
AB  - Five fresh osteochondral fractures of the knee, which could not be fixed because
      of extensive fragmentation, were treated by excision of the fragments and
      reconstruction of the joint surface defect by an autogenous osteoperiosteal
      graft. The procedure was also used for joint surface reconstruction in sclerotic
      osteochondritis of the femoral condyle (nine knees) and grave patellofemoral
      chondromalacia (three knees). Plaster cast immobilization for 3 weeks was used in
      the two early cases. In all other cases, we employed a passive motion apparatus
      for 2 days postoperatively, followed by active mobilization in a knee brace with
      extension-flexion 30 to 90 degrees (femoral condyle reconstruction) or 0 to 45
      degrees (patellar reconstruction). Gradual free movements were started 3 weeks
      postoperatively. The results after 1.5 to 6.5 years were satisfactory in all but
      one case. One arthroscopic removal of the loose graft was performed, as were two
      arthroscopic graft margin shavings. Three other reoperations were unrelated to
      the osteoperiosteal reconstruction. It appears that periosteal reconstruction
      should be considered in local osteochondral lesions, where excision of the
      injured cartilage is mandatory. The results were best in fresh trauma cases and
      younger people.

PMID- 7577213
TI  - Proliferating cell nuclear antigen staining as a prognostic indicator in soft
      tissue malignant fibrous histiocytoma.
AB  - To determine the value of proliferating cell nuclear antigen (PCNA) staining as a
      prognostic indicator in soft-tissue malignant fibrous histiocytoma (MFH), we
      studied 27 patients who underwent resection including an adequately wide margin
      but without chemotherapy. The survival rate of patients with a lesion in which
      less than 70% of the cells was positively stained was significantly higher (P <
      0.01) than of those with more than 70% positive staining. Twenty-two patients
      (81.5%) evidenced disease-free survival (mean follow-up period 4.6 years), 1
      patient was alive with disease, and 4 (14.8%) died of the disease with lung or
      lymph node metastasis. In all 4 patients who died, PCNA staining was over 70%
      positive. In 2 of them, an increase in the number of PCNA-positive cells was
      observed after repeated recurrence. We conclude that PCNA is a useful prognostic
      indicator which provides a quantitative measure of the grade of malignancy in MFH
      patients who receive operative treatment without chemotherapy.

PMID- 7577215
TI  - Prognostic significance of posterior subtalar joint arthrography following
      fractures of the calcaneus.
AB  - Nineteen patients with 22 intra-articular fractures of the calcaneus were
      investigated by posterior subtalar joint arthrography after 6 (2-15) months
      following injury, and their clinical symptoms were compared with the
      arthrographic findings. The arthrograms were classified into four types based on
      the findings of the joint space of the posterior subtalar joint in Anthonsen's
      view. The classification correlated significantly (P = 0.03) with the clinical
      results which were assessed after 23 (9-41) months following injury. We conclude
      that posterior subtalar joint arthrography has prognostic value in assessing
      patients with fractures of the calcaneus.

PMID- 7577217
TI  - Osteolysis, wear and failure of a migrating acetabular component. A roentgen
      stereophotogram case report.
AB  - The migration of an acetabular component, revised 12 years postoperatively, was
      clearly detectable within the first year after operation by roentgen
      stereophotogram analysis. The failure was probably the result of an early
      initiated prosthetic loosening.

PMID- 7577216
TI  - Allogeneic deep frozen meniscal graft for repair of osteochondral defects in the
      knee joint.
AB  - Osteochondral defects in the knee joints of five patients caused by trauma or
      osteochondritis dissecans were repaired using deep-frozen allogeneic meniscal
      grafts. Three patients were male and two were female, with a mean age of 26.4
      years. The mean follow-up period was 31 months. Postoperative magnetic resonance
      imaging (MRI) at all periods clearly showed a smooth and congruous articular
      surface, although the signal intensity of the grafted meniscus was not the same
      as that of the articular cartilage. Second-look arthroscopy performed
      approximately 1 year after surgery demonstrated that the grafted meniscus was
      well bonded to the grafted site, not sunken; there was no gap between the grafted
      meniscus and the surrounding articular cartilage, indicating that the grafted
      meniscus functions as a part of the articular surface. Histologic examination
      revealed that host cells had infiltrated into the meniscus and that cells
      surrounded by thin collagen fibrils were morphologically similar to
      fibrochondrocytes. Thus, the acellular grafted meniscus regenerated as meniscal
      tissue and formed an articular surface, although hyalinization did not occur. Our
      results suggest that deep-frozen allogeneic meniscal grafting is a useful method
      to repair osteochondral defects in the knee joint.

PMID- 7577219
TI  - False-positive sonographic hip examinations in newborns with congenital varus
      deformity of the proximal femur.
AB  - In cases of congenital varus deformity of the proximal femur, the screening of
      hip dysplasia can lead to misinterpretations. The false-positive ultrasound
      result is caused by the superiorly displaced greater trochanter in hips with coxa
      vara, which narrows the scan window. In this paper three typical patients are
      presented to demonstrate that the use of additional non-standard views cannot
      exclude hip dysplasia in all cases. Hence, such patients with femoral
      abnormalities and doubtful sonographic findings should be further evaluated by
      arthrography or magnetic resonance imaging to rule out additional hip dysplasia.

PMID- 7577218
TI  - Femoral head bone grafting for reconstruction of the acetabular wall in
      dysplastic hip replacement.
AB  - From 1980 through 1991 we screwed a preshaped cortico-cancellous bone graft onto
      the ileum wall to compensate acetabular deficiency in 94 consecutive total hip
      replacements. We report the results of 87 hips (79 patients) with an average
      follow-up of 30 months (12-75 months) postoperatively. Pain in dysplasia
      coxarthrosis and congenital dislocation of the hip, destructive coxitis in
      rheumatoid arthritis and cup loosening was the main indication for surgery.
      According to the Merle d'Aubigne score the postoperative clinical evaluation
      demonstrated 77% very good and 18% good results. Due to component loosening the
      results had to be classified as unsatisfactory in 4 hips (2 cups and 2 stems). At
      the time of evaluation 90% of the arthroplasties was osseously consolidated as
      evidenced by trabecular bridging and structural integrity with host bone.
      Resorptions of the graft were noted in 32 hips. One cup was removed because of
      complete resorption and consecutive loosening, a further one was considered
      clinically and radiologically loose because of partial graft resorption. Two
      further complete resorptions and 28 partial lateral resorptions had no influence
      on the secondary stability of the implant. We are aware that these are short-term
      results. Nevertheless, we recommend the described method as a valuable addition
      to arthroplasties for acetabular rim defects both in osteoarthritis and in
      revision surgery.

PMID- 7577221
TI  - Comparison of low-field (0.2 Tesla) and high-field (1.5 Tesla) magnetic resonance
      imaging of the knee joint.
AB  - In order to evaluate the reliability of low-field magnetic resonance imaging
      (MRI), we examined 22 patients using a 0.2-Tesla magnet unit in comparison with a
      1.5-Tesla system. The MRI findings were compared with the intraoperative
      findings. Concerning the diagnosis of meniscal tears, the gradings of both
      systems differed only in three cases. The specificity was 97% (both systems), the
      sensitivity 83% (1.5 T) versus 75% (0.2 T). The sensitivity and specificity for
      detection of tears of the anterior cruciate ligament were 100% and 75%,
      respectively, for both systems. The gradings differed only in two cases. In our
      series we found 6 full-thickness cartilage defects that were all detected with
      the high-field imaging system. They were missed by the low-field imaging system
      in 5 cases. The results suggest that both systems are reliable in diagnosing
      meniscal tears and ruptures of the anterior cruciate ligament.

PMID- 7577222
TI  - Computer-assisted assembly and correction simulation for complex axis deviations
      using the Ilizarov fixator.
AB  - In axis correction with the Ilizarov ring fixator, the correction results are
      often insufficient or there are unexpected translation effects, which can be
      causally attributed to wrong preoperative planning or inaccurate assembly. To
      avoid such results, computerised simulation was developed. Via digitalisation of
      the bone outlines traced from X-radiographs with an additional scale,
      preoperative correction planning can be performed, simulated with normal
      software. This can be used while constructing the apparatus and positioning the
      joints. In addition, the translation effect of the bone fragments can be
      simulated by arbitrarily choosing the pivot of the correction. In transferring
      the X-radiograph true to scale, one can compare the ring planes before and after
      correction. It is possible to estimate the necessary distraction as well as
      compression and thus the postoperative distraction mode. Using computerised
      planning, the apparatus construction can be optimised and complications caused by
      misplanning avoided. Not only the inexperienced user can benefit from this aid.

PMID- 7577220
TI  - Anterior cruciate ligament suture in comparison with plasty. A 5-year follow-up
      study.
AB  - In this retrospective study we analyse the results of primary anterior cruciate
      ligament (ACL) sutures, primary ACL plasties and secondary ACL plasties 5 years
      after operation. All operations were performed with an additional PDS
      augmentation. Follow-ups of 100 of 130 patients could be done (80 male and 20
      female). The average age at time of operation was 29.2 years. ACL rupture in 81
      patients occurred due to a sport accident. In 26 patients a primary ACL suture
      was performed, in 59 patients a primary ACL plasty and in 15 patients an ACL
      plasty due to instability. There was no difference between the primary and
      secondary plasty groups, but there was between the suture and the plasty groups.
      In all, 92% of the suture group and 69% of the plasty group were satisfied with
      the surgical results. The pivot shift, Lachman and anterior drawer sign were less
      frequent in the ACL suture group, and the Lysholm score was higher. Primary
      suture combined with a PDS augmentation seems to represent an adequate treatment
      of acute proximal ACL ruptures.

PMID- 7577223
TI  - Fascia lata plasty in recurrent posterior dislocation after total hip
      arthroplasty.
AB  - With a soft-tissue plasty, stability could be obtained in 17 of 22 patients with
      unstable hips after total hip arthroplasty. While in 16 of 18 patients with a
      posterior instability stability was achieved, only 1 of 3 patients with a
      unstable hip for dislocation in all directions was successfully treated. No
      stability could be achieved in one patient with a hip which dislocated
      anteriorly. The method described should only be used for posterior recurrent
      dislocations after total hip arthroplasty.

PMID- 7577224
TI  - Pharmacokinetic study of fibrin clot-ciprofloxacin complex: an in vitro and in
      vivo experimental investigation.
AB  - We prepared a composite of fibrin clot and ciprofloxacin for use as a
      biodegradable antibiotic delivery system with sustained effect for the treatment
      of chronic osteomyelitis. In vitro, ten experiments were performed in which 10 mg
      of ciprofloxacin were incorporated into 4 ml of fibrin clot. The clots were
      preserved in nutrient broth and incubated at 37 degrees C for a total of 60 days.
      Every 24 h a broth specimen was obtained, and the ciprofloxacin concentration was
      determined by microbiological assay. The maximum level of antibiotic was noted on
      the first day (49.9 +/- 5.1 mg/l). The ciprofloxacin-fibrin clot complexes
      usually disintegrated after 60 days. In vivo, the fibrin-ciprofloxacin clots were
      made as previously described. The composite was implanted in the medullary canal
      of rabbit tibiae, and the antibiotic concentration was measured in bone, muscle,
      skin and serum. In all tissues around the implant, the concentration of
      antibiotic exceeded the minimum inhibitory concentration against the common
      causative organisms of osteomyelitis for 10 days. The implant caused no systemic
      side-effects, and it is likely to prove clinically useful as a drug delivery
      system for treating chronic osteomyelitis.

PMID- 7577225
TI  - Reactivation of a tuberculous coxitis due to loosening of a total hip
      endoprosthesis.
AB  - A 45-year-old woman who suffered from juvenile tuberculous coxitis at the age of
      4 is presented. Her hip joint replacement lasted for 18 years and then needed
      replacing. Intraoperatively removed caseous soft tissue and an opalescent
      secretion histologically resembled a tuberculous focus, and bacteriological
      culture grew a Mycobacterium tuberculosis strain. Four months after the
      replacement, the patient suffered from a tuberculosis-induced septic loosening of
      the newly replaced hip joint endoprosthesis. The tuberculosis relapse was
      probably due to aseptic loosening of the first hip joint endoprosthesis.

PMID- 7577226
TI  - Architecture and polymorphism of fibrillar supramolecular assemblies produced by
      in vitro aggregation of human calcitonin.
AB  - The human calcitonin (hCT) peptide hormone has a marked tendency to aggregate in
      aqueous solutions and to form long, thin fibrillar aggregates resulting in
      viscous and turbid dispersions. In this study, the in vitro aggregation products
      of hCT were systematically investigated using conventional transmission electron
      microscopy (CTEM) and in-lens field emission scanning electron microscopy. The
      mass per length of unstained/air-dried specimens was determined by scanning
      transmission electron microscopy. Irrespective of the sample preparation method
      and electron microscopic (EM) imaging mode employed, similar supramolecular
      assemblies were observed. Based on these EM data, it is proposed that hCT
      aggregation begins with the formation of approximately 4-nm-thick protofibrils.
      These protofibrils further interact via lateral association and coiling to form
      higher-order fibrillar assemblies, i.e., protofibril-ribbons, fibrils, fibril
      ribbons, tubes, and multistranded cables. The concentration and history of the
      aggregated hCT solutions strongly influenced the relative frequency of the
      various hCT assemblies depicted. The supramolecular assemblies of hCT revealed
      distinct helical symmetries at their different levels of aggregation. A
      hypothetical mechanism assumed for aggregating solutions to form polymorphic
      fibrillar hCT assemblies is presented in a schematic model, and the
      supramolecular arrangement of hCT within the various polymorphic fibrillar
      aggregates is delineated.

PMID- 7577227
TI  - Human erythrocyte catalase: 2-D crystal nucleation and production of multiple
      crystal forms.
AB  - Negatively stained electron microscope images are presented, showing the
      nucleation of two-dimensional (2-D) crystals of human erythrocyte catalase
      produced on mica by the negative staining-carbon film technique. Examples of the
      formation of partially ordered 2-D arrays and more ordered 2-D crystals are shown
      and the conditions required for the production of large well-ordered 2-D crystals
      discussed. The structural transformation of one flexuous 2-D paracrystal into a
      p2 2-D crystal is considered. The crystallographic 2-D image average of this p2
      crystal form is presented (lattice parameters a = 9.0 nm, b = 18.6 nm, gamma =
      90.8 degrees). It is shown that transmission electron microscopy provides the
      possibility of defining 2-D crystal nucleation, growth of intermediate forms, and
      low-resolution crystallographic structural analysis of 2-D crystals of human
      erythrocyte catalase. Comparison of the various electron microscopical negatively
      stained images with the peptide backbone of the X-ray structure of bovine liver
      catalase at different tilt and rotation positions correlates with and emphasizes
      the multiple intermolecular contacts and orientations that can be adopted by
      human erythrocyte catalase, leading to various 2-D arrays and 2-D crystals.
      Alignment of the surface groups involved in the protein-protein interactions that
      occur during 2-D crystal nucleation and crystal growth may ultimately be
      determined. From this approach, when taken together with detailed consideration
      of protein-solvent and protein-solute electrostatic interactions in solution, and
      at the fluid-air interface, it is considered that a more general theory of
      crystal nucleation and growth may eventually emerge.

PMID- 7577229
TI  - Three-dimensional reconstruction of Androctonus australis hemocyanin labeled with
      a monoclonal Fab fragment.
AB  - An immunocomplex formed by the 4 x 6 meric hemocyanin of the scorpion Androctonus
      australis with the monoclonal antibody L104 was studied by cryoelectron
      microscopy and subjected to three-dimensional (3D) reconstruction. The
      reconstructed particle reflects the structure of the immunocomplex in its
      hydrated state and is devoid of the flattening that was previously observed with
      a negatively stained preparation. A 3D fitting of the X-ray data of the Panulirus
      interruptus hemocyanin and of the Fab R19.9 to the reconstruction volume allowed
      the first quantitative measurement of the structural parameters of the antigen,
      and the localization of the epitope at the surface of subunit Aa6. The
      independent alignment of the Fabs and the hexamers provides a direct verification
      for the accuracy of the fit and allows the building of the most detailed model of
      a cheliceratan 4 x 6meric complex and its attached monoclonal antibodies.

PMID- 7577230
TI  - Mechanism of the activation of proteinase inhibitor synthesis by systemin
      involves beta-sheet structure, a specific DNA-binding protein domain.
AB  - We analyzed a tertiary structure of systemin, the first identified polypeptide
      plant hormone, using two-dimensional NMR spectroscopy. From these data and
      molecular dynamics calculations we concluded that the peptide can adopt a Z-like
      beta-sheet structure, which has previously been found in many specific DNA
      binding proteins. Using DNA-cellulose affinity chromatography, we showed that
      systemin binds strongly to DNA. We suggest that the specific systemin-DNA
      interaction, particularly in a promoter region of the proteinase inhibitors,
      could effect gene expression and thus explain the biological activity of
      systemin.

PMID- 7577228
TI  - Crystallization and preliminary X-ray crystallographic studies on the adenovirus
      ssDNA binding protein in complex with ssDNA.
AB  - Crystals of the C-terminal domain of the adenovirus single-stranded DNA binding
      protein (DBP) in complex with the single-stranded oligonucleotide (dT)16 have
      been obtained by a batch method from material obtained by chymotryptic digest of
      full-length DBP. The colorless crystals grow as hexagonal prisms to a maximal
      size of approximately 0.85 x 0.55 x 0.55 mm. The spacegroup is P3(1)21 with unit
      cell constants a = 151.5 A and c = 124.0 A. There are either three or four
      molecules of DBP per asymmetrical unit. To improve the reproducibility of
      crystallization, recombinant protein has been produced using a baculovirus
      expression system and shown to crystallize under the same conditions.

PMID- 7577233
TI  - Theories of muscle contraction.
AB  - A survey of the mainstream theories in the modern study of the mechanism of
      muscle contraction is made, with particular emphasis placed on the experimental
      results which most influenced the progression of ideas. Starting with early
      elastic and viscoelastic theories of muscle contraction, a chronological
      organization is used to present, in detail, the results leading up to the
      swinging crossbridge model. A brief review is made of the experimental results
      modifying the original crossbridge model such as transient-state mechanics, in
      vitro kinetics, and kinetic measurements performed on demembranated muscle
      fibers. Following a brief synopsis of three of the more prevalent alternative
      models, a summary of the more relevant structural studies is presented. Finally,
      recent results pertaining to the mechanism of muscle contraction are presented
      and their promise for the future is discussed.

PMID- 7577232
TI  - The covalent structure of factor XIIIa crosslinked fibrinogen fibrils.
AB  - When factor XIIIa-mediated crosslinking of fibrin or fibrinogen occurs,
      reciprocal intermolecular isopeptide bonds form first between paired carboxy
      terminal gamma chain donor-acceptor sites in outer molecular D domains, resulting
      in gamma chain dimers. Their location in the fibrin polymer is not certain, but
      some evidence suggests they are situated at the outermost ends of the D domains
      of linearly aligned molecules comprising each strand of double-stranded fibrils
      ("DD-long"). Other experiments indicate that gamma chain bonds are located
      between D domains in opposing fibril strands ("transverse"). To distinguish
      between these possible arrangements, we evaluated the ultrastructure of fibrils
      and fibers found in factor XIIIa-fibrinogen crosslinking mixtures, based on this
      reasoning: if DD-long bonding occurs, single-stranded fibrils should result,
      whereas transverse positioning will result in double-stranded fibrils. Fibrils
      formed in partially cross-linked fibrinogen solutions consisted of two parallel
      strands, as discerned visually from scanning transmission electron microscopic
      images and confirmed by mass per unit length fibril measurements. Neighboring
      fibrinogen D domains in each fibril strand were aligned end-to-end and were in
      register with a fibrinogen E domain in the opposite strand, creating a half
      staggered molecular arrangement with approximately 22.5-nm periodicity
      corresponding to half the length of fibrinogen. Ribbon-like fibrinogen fibers,
      like fibrils, displayed 22.5-nm periodicity, as expected from laterally
      associated double-stranded fibrils with D domains in register. Taken together,
      these results indicate that carboxy terminal gamma chain bonds are positioned
      transversely between strands and are represented by thin filamentous structures
      bridging the D domains of opposing fibril strands--it follows that the same gamma
      chain crosslink arrangement occurs in fibrin.

PMID- 7577231
TI  - Evidence for amelogenin "nanospheres" as functional components of secretory-stage
      enamel matrix.
AB  - Amelogenins are the principal proteins of the extracellular matrix of developing
      dental enamel and are postulated to function in the processes of
      biomineralization of the developing tooth although the molecular mechanisms
      concerned are poorly understood. Recent imaging studies, employing dynamic light
      scattering, atomic force, and transmission electron microscopy (TEM) have shown
      that a recombinant amelogenin (M(r) approximately 20,000 Da) spontaneously forms
      supramolecular quasi-spherical aggregates ("nanospheres") of 15-20 nm in
      diameter. By comparison with in vitro experiments employing the recombinant
      amelogenin we show that the nanospheres appear as electron-lucent structures when
      treated with conventional electron microscopy contrast reagents (phosphotungstate
      or uranyl acetate) and we speculate that this property derives from the
      hydrophobic nature of the amelogenin protein. Employing TEM preparations of
      developing enamel from mouse, bovine, and hamster we demonstrate that the
      amelogenin nanospheres occur as beaded rows of electron-lucent structures aligned
      with, and separating, the enamel mineral crystallites. We postulate that the
      amelogenin monomers self-assemble to form nanospheres which function to space the
      initial crystallites, control crystal habit, inhibit intercrystalline fusions,
      and, through the apposition of their surfaces, create anionic channels which
      facilitate ion transport within the mineralizing matrix.

PMID- 7577234
TI  - Molecular model of an actin filament capped by a severing protein.
AB  - Gelsolin is a six-domain protein with a wide array of actin regulating
      activities. Despite the growing body of structural data on this protein, little
      is known about how it binds F-actin during severing and capping. In this paper we
      have combined data from X-ray crystallography, NMR, and electron microscopy to
      develop a model of an actin filament capped by a severing protein. The protein
      which we have modeled is G1/alpha A1-2, a genetically engineered molecule
      containing domains from both gelsolin and alpha-actinin. In the capped filament,
      domains G1 and alpha A1-2 of the hybrid severing protein bind two adjacent
      monomers along the long-pitch F-actin helix. The distance spanning these domains
      suggests the need for a flexible linker between them. By analogy, this implies
      that the gelsolin deletion mutant G1-3 contacts the same two monomers in the
      capped filament and suggests that the linker between G1 and G2 plays a crucial
      role in severing and capping.

PMID- 7577235
TI  - Solving the structure of macromolecular complexes with the help of X-ray fiber
      diffraction diagrams.

PMID- 7577236
TI  - Allostery, cooperativity, and different structural states in F-actin.
AB  - Electron microscopy and three-dimensional reconstructions have been used to show
      that F-actin can exist in multiple states. We have also been able to visualize
      large allosteric effects involving the C-terminus, the nucleotide binding site,
      the high-affinity metal-binding site, and the DNase I-binding loop. Further,
      there exists a large degree of cooper-activity in F-actin, such that
      conformational changes at one end of a filament may be transmitted to the other,
      distant, end. While many of these allosteric and cooperative effects have been
      previously suggested to exist based upon biochemical observations, we have been
      able to observe that these effects probably involve the movement of a large
      number of residues over significant distances. In systems such as muscle some of
      these conformational changes in F-actin may play an important role.

PMID- 7577237
TI  - Preliminary three-dimensional model for nematode thick filament core.
AB  - Understanding the structure and the mechanism of assembly of thick filaments have
      been long-standing problems in the field of muscle biology. Cores which represent
      the backbones of thick filaments and consist of paramyosin and associated
      proteins were isolated from the nematode Caenorhabditis elegans. Electron
      microscopy of negatively stained and frozen hydrated cores was performed. The
      resulting images were analyzed by computing their Fourier transforms, three
      dimensional reconstruction, and by modeling. A preliminary three-dimensional
      model is proposed in which the paramyosin constitutes an outer sheath of seven
      subfilaments about a set of inner 54-nm-long tubules which repeat every 72 nm.
      The subfilaments are not closely packed but require cross-linking by the internal
      tubules. Each subfilament consists of two strands of paramyosin molecules which
      are staggered by 72 nm with respect to one another. This stagger introduces a 22
      nm gap between consecutive paramyosin molecules in each strand. An offset of the
      center of the inner tubules relative to the center of the gap of 6 nm was
      consistent with the images and their transforms. This model suggests that the
      nonhelical ends of paramyosin and the unpaired gap between adjacent paramyosin
      molecules contain sites for the interaction with the inner tubular proteins. The
      molecular interactions at this locus would appear to be critical in the assembly
      of thick filaments and their regulation.

PMID- 7577239
TI  - A discourse on modeling F-actin.

PMID- 7577238
TI  - Fluorescence resonance energy transfer spectroscopy is a reliable "ruler" for
      measuring structural changes in proteins. Dispelling the problem of the unknown
      orientation factor.
AB  - Fluorescence resonance energy transfer (FRET) spectroscopy has been widely used
      to "measure" dimensions either within or between molecules over distances of 10
      100A, a range that is well suited to probing protein structure. The resolution of
      FRET spectroscopy is substantially lower than X-ray diffraction (XRD) but the
      technique makes up for this deficit by being particularly good at measuring
      structural changes in proteins. However, absolute distances measured by FRET
      spectroscopy remain problematical because of what appears to be an unjustified
      assumption, namely that calculations of FRET distances assume that the probes are
      able to undergo free, isotropic motion. This uncertainty may be ascribed to an
      unknown value for the orientation factor, but other factors may also be
      important. Common sense suggests that a large (300-500 Da) hydrophobic FRET probe
      covalently bound to an amino acid side chain of a protein can not undergo true
      rotational freedom. If this is so, the calculated distances would at best be
      flawed and at worst be meaningless. In this paper we argue that the orientation
      parameter is no longer an important issue in the determination of distances
      determined by FRET using peptides and proteins. Furthermore, we suggest that FRET
      may be a good form of spectroscopy for testing models of F-actin.

PMID- 7577240
TI  - Preservation of 2-D crystals of tubulin for electron crystallography.
AB  - Zinc-induced sheets of tubulin are two-dimensional crystalline polymers that
      constitute an ideal sample for high resolution studies of tubulin by electron
      crystallography. We show that these 2-dimensional tubulin crystals can be
      stabilized by taxol against low-temperature depolymerization and degradation with
      time, easing the way for the preparation of electron microscopy samples. The
      preservation of the crystals to high resolution has been tested with different
      embedding media. While glucose-embedded samples diffract poorly, samples embedded
      in tannin consistently diffract to a resolution of at least 3.5 A. Even better
      results are obtained by embedding with a combination of tannin and glucose, which
      improves the flatness of the crystals and allows the collection of isotropic high
      resolution data from tilted specimens.

PMID- 7577242
TI  - Results of the CANNT technical survey.

PMID- 7577245
TI  - Decreasing hypotensive episodes on hemodialysis.

PMID- 7577241
TI  - A 7-A projection map of frozen, hydrated acrosomal bundle from Limulus sperm.
AB  - The acrosomal bundle from Limulus sperm has been imaged to 7 A in a 400-kV
      electron cryomicroscope using the spot-scan technique. These images have been
      processed by Fourier averaging, corrected for the contrast transfer function, and
      merged to that resolution. The reconstructed density map of this projection shows
      features consistent with the 13-A projection map from a helical reconstruction
      and with the X-ray-derived model for F-actin, and regions of possible scruin
      scruin contacts.

PMID- 7577244
TI  - Acute paediatric hemodialysis.

PMID- 7577243
TI  - CANNT standards for nephrology technical practice.

PMID- 7577246
TI  - Inflammatory mediators of pain.
AB  - While sensory fibres normally respond to a range of physical and chemical stimuli
      their activity and metabolism are profoundly altered by a variety of mediators
      generated by tissue injury and inflammation. These include substances produced by
      damaged tissue, substances of vascular origin as well as substances released by
      afferent fibres themselves, sympathetic fibres and various immune cells. The
      effects of inflammatory mediators, to activate or sensitize afferent fibres, are
      produced by changing membrane ion channels which are coupled directly via
      receptors or more commonly are regulated through receptor-coupled second
      messenger cascades. These latter processes also have the potential to alter gene
      transcription and thereby induce long-term alterations in the biochemistry of
      sensory neurones. This can have far-reaching consequences as the expression of
      novel proteins for ion channels (Na channels) and receptors (capsaicin, NPY) as
      well as the induction of novel enzymes (i-NOS) can profoundly affect the
      properties of nociceptors and their ability to transmit pain signals. However,
      such changes may be targeted successfully for the development of new analgesic
      and anti-inflammatory agents.

PMID- 7577247
TI  - Visceral pain.

PMID- 7577248
TI  - New molecules in analgesia.

PMID- 7577250
TI  - Somatic pain--pathogenesis and prevention.

PMID- 7577249
TI  - Capsaicin and pain mechanisms.

PMID- 7577251
TI  - Developmental biology of inflammatory pain.

PMID- 7577252
TI  - Molecular biology of pain.
AB  - We have attempted to define some of the patterns of expression of the IEG Fos in
      pain-related states. On one level, Fos may be used simply as marker of afferent
      stimulation and disease state, and in this respect Fos activation may be a useful
      tool after nociceptive stimulation to examine the effectiveness of different
      analgesic regimens. For example, certain analgesics such as opioids, alpha 2
      agonists and local anaesthetics are more effective when given pre-emptively or
      early in the injury rather than later on. Furthermore, the persistent expression
      of Fos in the presence of high dose pre-emptive opioids is disturbing and yet it
      may explain variable success of studies attempting to show pre-emptive analgesia
      with opioid-based analgesic regimens. We suggest that Fos expression, as well as
      defining the magnitude and the duration of insult to the spinal cord seems also
      to signal the adaptive responses of the nervous system to nociceptive insult.
      Though we have focused on only one IEG, c-fos, and attempted to relate appearance
      to known functional changes within the spinal cord, there are in fact many more
      genes known to be upregulated with the same or slower kinetics (e.g. Fos B, FRA
      1, FRA-2, Jun B, Jun D, NGFI-A). Increased understanding of the role of these
      genes is likely to lead to many novel targets in the search for normalization or
      restoration of spinal cord function in pain states and after nerve injury.

PMID- 7577253
TI  - Spinal cord pharmacology of pain.

PMID- 7577254
TI  - Nerve growth factor regulates nociception in human health and disease.

PMID- 7577255
TI  - Imaging pain in humans.

PMID- 7577256
TI  - Descending control of pain.
AB  - Thanks largely to the study of the brainstem nuclei that mediate stimulation
      analgesia, the involvement of the monoamines in the descending control of pain is
      now well established. The periaqueductal grey, the raphe nuclei (NRM and DRN) and
      the locus coeruleus are all key brainstem sites for the control of nociceptive
      transmission in the spinal cord. Although the initial emphasis was on 5-HT as the
      transmitter mediating this control at spinal levels, it is clear from more recent
      work that NA has an equally important part to play. How (or even if) the two
      amines differ in their roles and actions in analgesia is, however, still an open
      question. The small size and complexity of the brainstem areas from which
      analgesia may be elicited by electrical stimulation complicates the
      interpretation of the data. Stimulating currents may spread to surrounding
      regions mediating opposite effects to that of the main region stimulated. Opiates
      and GABA are clearly involved in descending control at both brainstem and spinal
      levels, although the relative roles of the different types of amino-acid and
      opiate receptors is still hotly debated. Despite the fact that the first report
      on stimulation analgesia appeared more than a quarter of a century ago in 1969,
      the precise connections and cord synaptology are still the basis of ongoing
      research. It is perhaps ironic, in an issue dedicated to new molecules and
      mechanisms, that those transmitters most involved in descending inhibition should
      be such old and familiar friends.

PMID- 7577257
TI  - Subarachnoid spread of isobaric tetracaine in adolescents.

PMID- 7577259
TI  - Comparison of ropivacaine and bupivacaine for extradural analgesia.

PMID- 7577258
TI  - Aprotinin therapy.

PMID- 7577260
TI  - Animal toxins: Scorpaenidae and stingrays.

PMID- 7577261
TI  - Detection of accidental oesophageal intubation.

PMID- 7577262
TI  - Ambulatory extradural analgesia.

PMID- 7577263
TI  - Gastric mucosal pH and splanchnic blood flow.

PMID- 7577265
TI  - Optimum opioid for extradural administration.

PMID- 7577264
TI  - Positive pressure ventilation and the laryngeal mask airway in ophthalmic
      anaesthesia.

PMID- 7577266
TI  - Cannabis as a medicine.

PMID- 7577267
TI  - Cardiac arrest after unrecognized dynamic inflation.

PMID- 7577268
TI  - General anaesthesia for day-case cataract surgery.

PMID- 7577269
TI  - Design of nitric oxide delivery systems.

PMID- 7577270
TI  - Maternal sequelae of childbirth.

PMID- 7577271
TI  - Ensuring adequate cerebral perfusion during aneurysm surgery.

PMID- 7577272
TI  - The risk of extradural abscess.

PMID- 7577274
TI  - Effects of changes in mean arterial pressure on SjO2 during cerebral aneurysm
      surgery.
AB  - Twenty-six patients requiring clipping of cerebral aneurysms were anaesthetized
      with propofol, alfentanil and atracurium infusions and their lungs ventilated
      mechanically to hypocapnia (3.4-4.5 kPa). SjO2 was measured continuously with an
      Oximetrix fibreoptic oximetry catheter. Normovolaemia was maintained by observing
      the response of mean arterial pressure (MAP) and central venous pressure (CVP) to
      fluid administration. The response of SjO2 to increased MAP was noted and the
      lactate oxygen index (LOI) calculated at regular intervals. SjO2 measurements
      indicated a critical MAP of between 80 and 110 mm Hg in nine patients, and one
      patient had a persistently low SjO2 value despite an MAP of 110 mm Hg. An
      increase in MAP was associated with an increase in SjO2 in 19 patients (P <
      0.001). When the effects of changes in PaCO2 were eliminated, this change was
      still significant (P = 0.004) (n = 9). Patients with an LOI > 0.08 at any time
      during the procedure had a worse initial outcome (within the first day) (P <
      0.02) than patients who had a normal LOI throughout. Long-term outcome was
      similar to those with a normal LOI. Increasing MAP did not have a consistent
      effect on LOI. Jugular bulb cannulation to assess hypoperfusion in conjunction
      with lactate measurements and calculation of LOI provide useful information on
      which to base the intra- and postoperative management of patients with
      subarachnoid haemorrhage.

PMID- 7577273
TI  - Neurological complications associated with pregnancy.
AB  - Prospective multidisciplinary audit from both hospital and community has
      identified neurological complications persisting for more than 6 weeks in
      association with pregnancy and delivery. They occurred at a frequency of 1 in
      2530 deliveries in the North West Thames Region. Extradural analgesia was
      considered contributory to a neurological disorder in one of 13,007 patients. The
      woman had prolonged paraesthesiae along a nerve root. The types of sensory, motor
      and sympathetic neurological problems presented ranged from transient problems to
      more serious disorders resulting in death in one case. Seven of 19 patients had a
      continuing neurological disability for more than 1 yr. Although obstetrics may be
      associated with lumbar and sacral neurological disorders, problems occurred with
      the same frequency in the upper as in the lower half of the body. Significant
      morbidity is not being recognized in hospitals where women are being delivered
      and it is within the community that these disorders are recognized. This has
      implications for training, audit and risk assessment.

PMID- 7577276
TI  - Extradural anaesthesia for repeated surgical treatment in the presence of
      infection.
AB  - The use of extradural catheters in patients with systemic or localized infection
      is controversial. The catheter may act as a focus for secondary infection
      resulting in an extradural abscess. in this study we have examined the use of
      extradural catheters for anaesthesia over the past 7 yr in patients with
      localized infections. The records of 69 patients were reviewed and patients
      interviewed (letter/phone). These patients had a total of 120 extradural
      catheters placed and received, on average, four anaesthetics, with the extradural
      catheter remaining in place for a mean of 9 days. On 12 occasions (eight
      patients) the catheter was removed because of signs or symptoms of local
      infection. Specific antibiotic therapy was not initiated, but ongoing therapy was
      continued. A single case of spondylitis was the only serious complication found
      but was not related to the extradural technique. We conclude that extradural
      anaesthesia for patients who require repeated surgical treatments for abscesses
      or infected wound is a relatively safe procedure.

PMID- 7577277
TI  - Extradural, paravertebral and intercostal nerve blocks for post-thoracotomy pain.
AB  - Forty-five patients were allocated randomly to receive either a single
      intrathoracic block of four intercostal nerves, a continuous thoracic extradural
      infusion or a continuous paravertebral infusion of bupivacaine. Patients were
      allowed additional i.v. boluses of morphine via a PCA device. Segmental spread of
      pinprick analgesia was comparable in the groups for up to 20 h. Up to 2 h after
      the block, plasma concentrations of bupivacaine were greater in the intercostal
      group and there was large interindividual variation. There were no significant
      differences between the groups in pain, morphine consumption, respiratory
      function or adverse events. Moderate to severe respiratory depression was
      detected in 14 patients more than 2 h after operation.

PMID- 7577275
TI  - Effect of crystalloid and colloid preloading on uteroplacental and maternal
      haemodynamic state during spinal anaesthesia for caesarean section.
AB  - We have studied the effects of crystalloid 1 litre (lactated Ringer's) or colloid
      0.5 litre (hydroxyethyl starch) preloading in 26 healthy parturients undergoing
      elective Caesarean section under spinal anaesthesia. Maternal placental uterine
      artery circulation was measured using a pulsed colour Doppler technique with
      simultaneous measurement of maternal haemodynamics. A high incidence of maternal
      hypotension was observed during spinal anaesthesia in the crystalloid group (62%)
      but the incidence was lower in the colloid group (38%). Central venous pressure
      was increased significantly in both groups after preload but decreased shortly
      after induction of spinal anaesthesia to baseline values. The mean pulsatility
      index (PI) in the uterine arteries did not change during preload or spinal block.
      A surprising finding was the widespread variation and some high values for the
      uterine artery PI after spinal anaesthesia. These individual increases in PI were
      transient and always returned to baseline values within 2 min. These results
      suggest that preloading with either solution is ineffective in preventing
      maternal hypotension and that changes in maternal heart rate, systolic arterial
      pressure and central venous pressure during spinal anaesthesia were not
      associated with rapid individual increases in uteroplacental vascular resistance.
      These changes seemed not to have any major effect, however, on the clinical
      condition of the newborn, as assessed by Apgar scores and umbilical artery pH
      values.

PMID- 7577278
TI  - Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and
      mepivacaine-butorphanol mixtures for postoperative analgesia.
AB  - We have reported recently that continuous administration of butorphanol into the
      brachial plexus sheath provided analgesia of a quality superior to that of
      continuous i.v. administration. In the present study, we have compared
      postoperative pain relief produced by continuous infusion of one of three types
      of solution into the axillary sheath: opioid alone, local anaesthetic alone or a
      mixture of local anaesthetic and opioid. In patients undergoing upper extremity
      surgery with continuous axillary brachial plexus block, we injected one of the
      three solutions into the axillary neurovascular sheath: butorphanol 2 mg (group
      B), 0.5% mepivacaine alone (group M) and 0.5% mepivacaine-butorphanol (group MB);
      the volume of each solution was 50 ml, administered at a rate of 50 ml per 24 h.
      At 3 h after operation, visual analogue scale (VAS) scores were significantly
      higher in group M than in group MB (P < 0.01), and higher in group B than in
      group MB (P < 0.05).

PMID- 7577280
TI  - Prevention of vomiting after paediatric strabismus surgery: a systematic review
      using the numbers-needed-to-treat method.
AB  - Randomized controlled studies were reviewed to assess the effectiveness and
      safety of antiemetics used for prophylaxis in paediatric strabismus surgery.
      Early and late vomiting (6 and 48 h after operation, respectively), and adverse
      effects were evaluated using the numbers-needed-to-treat method. In 27 reports
      with information on 2033 children, the mean incidence of early vomiting was 54%
      and of late vomiting 59%, without prophylaxis. Only three drugs were studied
      sufficiently for firm conclusions to be drawn. In the best documented regimen
      (droperidol 75 micrograms kg-1), four children have to be given the drug to
      prevent one vomiting; of the three others, one may vomit and two would not have
      vomited anyway; fewer than one child in 100 may have an extrapyramidal reaction
      and 16 may have minor adverse effects. Metoclopramide 0.15 and 0.25 mg kg-1 was
      significantly better than control only for early vomiting. Propofol had a high
      incidence of oculocardiac reflex without conferring any significant antiemetic
      effect: it should not be used. The benefits of prophylactic antiemetic therapy
      are not proven.

PMID- 7577279
TI  - Intra-articular analgesia for arthroscopic meniscectomy.
AB  - Intra-articular morphine has been shown to provide prolonged analgesia after
      arthroscopic knee surgery; the addition of local anaesthetic agents has been
      reported to improve this analgesic effect. Pethidine possesses local anaesthetic
      properties, and therefore this study was designed to evaluate its analgesic
      efficacy after arthroscopic meniscectomy. Sixty patients were allocated randomly
      to receive intra-articular injections of pethidine 50 mg, morphine 5 mg or saline
      after elective arthroscopic meniscectomy. Postoperative pain was assessed using
      an interval visual analogue scale and measuring analgesic requirements. Both
      treatment groups had significantly lower pain scores compared with the control
      group. Patients in the pethidine group had lower pain scores than those in the
      morphine group at 0.5, 1 and 2 h, but significantly higher scores at 12 and 24 h.
      These observations suggest that the local anaesthetic effect of pethidine may be
      responsible for the improved early analgesia, but its duration of action appears
      to be less than that of morphine.

PMID- 7577282
TI  - Conventional pneumoperitoneum compared with abdominal wall lift for laparoscopic
      cholecystectomy.
AB  - We have compared, in a randomized study, conventional carbon dioxide
      pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic
      cholecystectomy. Intra-abdominal pressure (IAP) (11 (SD 2) mm Hg vs 2.7 (9) mm
      Hg) (P < 0.01) and total amount of carbon dioxide used (40 (23) litre vs 9 (7)
      litre) (P < 0.001) were significantly less with abdominal wall lift. Pulmonary
      compliance was significantly greater (P < 0.01) in the abdominal wall lift group
      throughout operation. During the first 15 min of insufflation, arterial pressures
      were lower with abdominal wall lift (P < 0.05). In the conventional
      pneumoperitoneum group, femoral vein pressure increased (P < 0.01) and remained
      elevated for 3 h in the recovery room. Postoperative drowsiness was of
      significantly longer duration in the conventional pneumoperitoneum group than in
      the abdominal wall lift group (98 (46) min vs 13 (34) min) (P < 0.01).
      Postoperative nausea and vomiting and right shoulder pain occurred more often in
      patients with conventional pneumoperitoneum (P < 0.05). We conclude that the
      benefits of abdominal wall lift may be attributed to avoiding excessive carbon
      dioxide and high IAP.

PMID- 7577283
TI  - Effect of i.v. lignocaine on the breathing of patients anaesthetized with
      propofol.
AB  - Local anaesthetics are ventilatory depressants, but previous investigators have
      not commented on the effects on ventilatory timing. There is concern about the
      possible ventilatory depression caused by systemic absorption of local
      anaesthetics injected extradurally. We have studied ASA grade I patients
      anaesthetized with a propofol infusion and breathing spontaneously; they were
      given in random order lignocaine 1.5 mg kg-1 i.v. and an equivalent volume of
      0.9% saline. Breathing was analysed using respiratory inductance plethysmography
      in 30-s periods for 4 min after injection, each period scaled to the 30-s period
      preceding injection. Lignocaine reduced minute ventilation. The greatest mean
      reduction in the 4 min was to 85%, occurring 2.5-3 min after injection; the
      greatest individual reduction was to 60-65%, which occurred by 30-60 s.
      Lignocaine decreased tidal volume and ventilatory rate by prolonging expiratory
      time. Lignocaine had no effect on or promoted bimodality of expiratory time. End
      tidal carbon dioxide increased by a mean of 0.1%; the largest individual change
      was 0.3%. This suggests that lignocaine may have reduced the metabolic rate,
      affecting ventilation indirectly, but we conclude that lignocaine in a normal
      extradural dose should not be an important ventilatory depressant.

PMID- 7577281
TI  - Manual compared with target-controlled infusion of propofol.
AB  - We studied 160 ASA I-II patients, anaesthetized with propofol by infusion, using
      either a manually controlled or target-controlled infusion system. Patients were
      anaesthetized by eight consultant anaesthetists who had little or no previous
      experience of the use of propofol by infusion. In addition to propofol, patients
      received temazepam premedication, a single dose of fentanyl and 67% nitrous oxide
      in oxygen. Each consultant anaesthetized 10 patients in sequential fashion with
      each system. Use of the target-controlled infusion resulted in more rapid
      induction of anaesthesia and allowed earlier insertion of a laryngeal mask
      airway. There was a tendency towards less movement in response to the initial
      surgical stimulus and significantly less movement during the remainder of
      surgery. Significantly more propofol was administered during both induction and
      maintenance of anaesthesia with the target-controlled system. This was associated
      with significantly increased end-tidal carbon dioxide measurements during the
      middle period of maintenance only, but recovery from anaesthesia was not
      significantly prolonged in the target-controlled group. With the exception of a
      clinically insignificant difference in heart rate, haemodynamic variables were
      similar in the two groups. Six of the eight anaesthetists found the target
      controlled system easier to use, and seven would use the target-controlled system
      in preference to a manually controlled infusion. Anaesthetists without prior
      experience of propofol infusion anaesthesia quickly became familiar with both
      manual and target-controlled techniques, and expressed a clear preference for the
      target-controlled system.

PMID- 7577284
TI  - Comparison of the effects of propofol and isoflurane anaesthesia on right
      ventricular function and shunt fraction during thoracic surgery.
AB  - I.v. anaesthetic agents, including propofol, have not been shown to inhibit
      hypoxic pulmonary vasoconstriction (HPV). This may encourage the use of propofol
      in thoracic surgery where one lung ventilation (OLV) is required. We have
      compared the effects of maintaining anaesthesia with either isoflurane or
      propofol infusion on right ventricular function and shunt fraction. We studied 10
      patients who received isoflurane and 12 who received propofol. When OLV commenced
      there was a greater reduction in both mean cardiac index (3.2 (SEM 0.2) to 2.4
      (0.1) litre min-1 m-2 for propofol, and 3.4 (0.2) to 3.3 (0.4) litre min-1 m-2
      for isoflurane) and right ventricular ejection fraction (0.45 (0.03) to 0.37
      (0.02) for propofol, and 0.48 (0.02) to 0.42 (0.02) for isoflurane) in patients
      who received propofol. Furthermore, these reductions were sustained for longer in
      the propofol group. However, propofol was not associated with a significant
      increase in shunt fraction during OLV, which increased threefold in patients who
      received isoflurane.

PMID- 7577287
TI  - Effects of clonidine premedication on the pressor response to alpha-adrenergic
      agonists.
AB  - It has been suggested that postjunctional alpha 1-adrenoceptor mediated
      vasoconstriction is enhanced by clonidine. We have examined in humans if the
      pressor responses to noradrenaline and phenylephrine are enhanced by clonidine
      premedication. Seventy-seven patients were allocated randomly to either clonidine
      (n = 38) or control (n = 39) groups. Patients in the clonidine group received
      approximately 5 micrograms kg-1 with famotidine 20 mg, while the control group
      received famotidine 20 mg alone orally, 90 min before induction of general
      anaesthesia with thiamylal. In all patients the lungs were ventilated
      mechanically via tracheal tubes and anaesthesia maintained with 1% end-tidal
      enflurane and 67% nitrous oxide in oxygen. When a stable haemodynamic state was
      obtained, either noradrenaline 0.5 microgram kg-1 (n = 40) or phenylephrine 2
      micrograms kg-1 (n = 37) was administered randomly i.v. as a bolus, while
      arterial pressure and heart rate were measured noninvasively at 1-min intervals
      for 10 min. Although noradrenaline caused significantly greater increases in mean
      arterial pressure (MAP) in the clonidine group (from 2 to 4 min after i.v.
      injection) compared with the control group, there were no significant differences
      in the mean maximal increment in MAP or area under the MAP curve between the two
      groups. However, i.v. phenylephrine produced a significantly greater increase in
      MAP from 2 to 7 min (P < 0.05), and greater mean maximal increase in MAP from the
      baseline value (21 (9) vs 14 (7) mm Hg; P < 0.05) in the clonidine than in the
      control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577290
TI  - Haemodynamic response to simulated haemorrhage in the rabbit: interaction of i.v.
      anaesthesia and hypoxia.
AB  - We have studied in eight rabbits the cardiovascular effects of midazolam,
      propofol and alfentanil with graded hypoxia. Central blood volume was reduced
      progressively by gradual inflation of a thoracic vena cava cuff so that cardiac
      index (CI) decreased at a constant rate. Under control conditions the
      haemodynamic response was biphasic. During phase I, mean arterial pressure (MAP)
      was maintained by a progressive decrease in systemic vascular conductance (SVCI).
      When CI had declined to a critical level, phase II occurred with an abrupt
      increase in SVCI and decrease in MAP. Phase I was prolonged by hypoxia,
      alfentanil and midazolam, but the effects were not additive. Phase I was
      shortened by propofol and this effect increased with hypoxia. The gradient of the
      SVCI response in phase I was also reduced by propofol > midazolam, but not by
      alfentanil. The occurrence of phase II was less frequent during alfentanil
      infusion than midazolam and propofol with all of the inspired gas mixtures. Thus
      the opioid was protective against circulatory collapse with hypoxia and simulated
      hypovalaemia.

PMID- 7577286
TI  - Histamine-release haemodynamic changes produced by rocuronium, vecuronium,
      mivacurium, atracurium and tubocurarine.
AB  - We have examined the effects of different benzyl-isoquinolinium and steroidal
      neuromuscular blocking compounds on plasma concentrations of histamine, heart
      rate and arterial pressure in surgical patients. A single, rapid (5-s) bolus of
      mivacurium 0.2 mg kg-1, atracurium 0.6 mg kg-1, tubocurarine 0.5 mg kg-1,
      vecuronium 0.1 mg kg-1 or rocuronium 0.6 mg kg-1 was administered to 75 patients
      (n = 15 in each group). Anaesthesia was induced with thiopentone 6 mg kg-1 i.v.
      and maintained with isoflurane and 70% nitrous oxide in oxygen. Venous blood
      samples were obtained before induction, 1 min after thiopentone and 1, 3 and 5
      min after administration of the neuromuscular blocking drug. Mivacurium,
      atracurium and tubocurarine caused 370%, 234% and 252% increases in plasma
      histamine concentrations at 1 min, respectively. Corresponding values at 3 min
      were 223%, 148% and 157%, respectively. These changes were significant (P < 0.01)
      at 1 and 3 min. In contrast, the rocuronium and vecuronium groups had no
      significant changes in either plasma histamine concentrations or haemodynamic
      variables.

PMID- 7577285
TI  - Assessment of changes in left ventricular wall stress from the end-systolic
      pressure-area product.
AB  - We have measured the left ventricular (LV) end-systolic (ES) pressure-area
      product in 30 patients under general anaesthesia. We multiplied systolic arterial
      pressure with the ES cavity area obtained by transoesophageal echocardiography,
      and compared the product with M-mode derived ES wall stress before and during
      cardiovascular treatment. To attain appropriate mean arterial pressure during
      major non-cardiac surgery, 10 hypertensive patients required treatment with
      nitroglycerin, 10 septic patients received noradrenaline and 10 patients with
      intraoperative cardiac failure were given adrenaline. Baseline values and
      relative changes in the ES pressure-area product correlated well (r = 0.85 and r
      = 0.87; P < 0.05) with those of ES wall stress. Changes in the ES pressure-area
      product by more than 10% reflected ES wall stress changes with a sensitivity of
      88% and a specificity of 94%. With adrenaline, the ES pressure-area product and
      ES wall stress did not change significantly, while systemic vascular resistance
      increased by 20%. The ES pressure-area product seems suitable for the detection
      of intraoperative LV wall stress changes.

PMID- 7577289
TI  - Dependence of pulmonary venous admixture on inspired oxygen fraction and time
      during regional hypoxia in the rabbit.
AB  - In order to examine the value of assuming constant pulmonary venous admixture
      with respect to changes in inspired oxygen fraction (FIO2) and time during
      sustained unilateral hypoxia, we studied venous admixture for 6 h in 27
      anaesthetized rabbits in which the left lung was filled with liquid, isosmotic
      with plasma. In one group of 10 rabbits the right lung was ventilated for 6 h
      with FIO2 = 1; in a second group of 10 the right lung was ventilated with FIO2 =
      1 for 2.5 h and then with FIO2 = 0.3 for 3.5 h. A third group was similarly
      studied by changing from FIO2 = 1 to FIO2 = 0.5. We found that hypoxic pulmonary
      vasoconstriction continued to intensify over 3 h. At 3-6 h, with FIO2 = 0.3,
      venous admixture (0.32 (SEM 0.03)) was higher than baseline (0.13 (0.01), t = 0
      min during bilateral oxygenation) by twice the elevation above baseline of the
      venous admixture (0.22 (0.01)) in the group with FIO2 = 1. The finding of a
      marked increase in venous admixture with decreasing FIO2 is discussed in relation
      to current models of hypoxic pulmonary vasoconstriction.

PMID- 7577288
TI  - Surgical stimulation increases median nerve somatosensory evoked responses during
      isoflurane-nitrous oxide anaesthesia.
AB  - Median nerve somatosensory evoked responses (MnSSER) were recorded in 15 healthy
      adult patients, ASA I-II, before and during orthopaedic surgery. After induction
      of anaesthesia with fentanyl 0.1-0.15 mg, etomidate 0.3 mg kg-1 and vecuronium
      0.1 mg kg-1, anaesthesia was maintained with 0.6% isoflurane (end-tidal) and 66%
      nitrous oxide in oxygen. MnSSER were recorded after establishment of steady-state
      anaesthesia at baseline, during preparation (n = 11) and continuously after the
      start of surgery. For the last measurement period, four patients were excluded
      from analysis because additional fentanyl was required. MnSSER were recorded at
      Erb's point, at C6 (neck) and at the respective contralateral primary
      somatosensory projection area (C3' or C4'). All MnSSER waveform components
      remained recordable and easily identifiable during anaesthesia. During intense
      surgical stimulation (e.g. periosteal stimulation) the peak-to-peak amplitude
      N20P25 increased significantly by more than 45% (P < 0.05), whereas latencies of
      all components did not change over time. These data indicate that MnSSER may be
      reliably monitored in the intraoperative period during steady-state isoflurane
      nitrous oxide anaesthesia. In addition, concurrent changes in haemodynamic
      variables during nociceptive stimulation support the hypothesis that reversal of
      isoflurane-nitrous oxide-induced suppression of MnSSER may indicate increased
      nociceptive input when depth of anaesthesia is inadequate.

PMID- 7577292
TI  - Prevention of postoperative venous thromboembolism.

PMID- 7577294
TI  - Temporal summation during extradural anaesthesia.
AB  - We have investigated in 10 patients the effect of extradural anaesthesia on
      temporal summation by comparing pain thresholds to single and repeated (five
      impulses at 2 Hz) electrical stimuli and compared these tests with pinprick and
      cold stimulation. Bupivacaine 0.5% (20 ml) was injected at L2-3. After extradural
      anaesthesia the threshold to repeated stimuli was significantly lower than the
      threshold to single stimuli (P = 0.0007). Nine patients lost cold sensation and
      10 patients pinprick sensation. Pain to single electrical stimulation disappeared
      in six patients and pain to repeated electrical stimulation in one. Pain may be
      evoked by temporal summation of repeated electrical stimuli even when pinprick
      sensation, cold sensation and pain to single electrical stimuli are inhibited.
      Thus temporal summation should be taken into consideration when extradural
      analgesia is assessed.

PMID- 7577293
TI  - Effect of nebulized lignocaine on airway irritation and haemodynamic changes
      during induction of anaesthesia with desflurane.
AB  - This study was designed to assess the effect of nebulized lignocaine or saline
      given before induction on the quality of induction of anaesthesia with desflurane
      in unpremedicated, young, adult males. Of the first six patients, five developed
      laryngospasm, breath-holding, coughing and increased secretions. In four patients
      oxygen saturation decreased to 92% or less. Significant tachycardia and
      hypertension occurred in four patients, and bradyarrhythmia after induction
      occurred in three patients. Hiccups and bronchospasm occurred in one patient.
      Because of the unacceptably high incidence of complications, the study was
      discontinued. The incidence and severity of complications were not decreased by
      administration of nebulized lignocaine and were higher than those reported by
      other workers. We conclude that in unpremedicated, young, adult males, induction
      of anaesthesia with desflurane and nitrous oxide in oxygen was associated with a
      high incidence of respiratory irritant effects, tachycardia, hypertension and
      post-induction bradyarrhythmia. We also found that lignocaine, as used in this
      study, did not appear to obtund the cardiovascular and respiratory complications
      during inhalation induction using desflurane.

PMID- 7577291
TI  - Effects of graded infusion rates of propofol on cardiovascular haemodynamics,
      coronary circulation and myocardial metabolism in dogs.
AB  - We have studied the effects of a 30-min infusion of propofol 6, 9, 12, 15, 18 and
      21 mg kg-1 h-1 on cardiovascular haemodynamics, coronary circulation and
      myocardial metabolism in 12 mongrel dogs. Mean plasma concentrations of propofol
      after infusion of 6 and 21 mg kg-1 h-1 increased from 2.9 (SEM 0.3) to 11.5 (0.1)
      micrograms ml-1. Propofol produced a progressive decrease in arterial pressure.
      Heart rate tended to decrease at 15, 18 and 21 mg kg-1 h-1 and cardiac index
      decreased significantly at infusion rates > or = 9 mg kg-1 h-1. Systemic vascular
      resistance tended to increase except at 21 mg kg-1 h-1 and left ventricular
      systolic and diastolic function were depressed. Both coronary sinus blood flow
      and myocardial oxygen consumption decreased in parallel with a decrease in left
      ventricular minute work index without producing lactate. Propofol produced
      progressive decreases in coronary blood flow and myocardial oxygen consumption
      but did not exert adverse effects on the coronary circulation.

PMID- 7577296
TI  - Anaesthetic management of caesarean section in a patient with active recurrent
      genital herpes and AIDS-related dementia.
AB  - We report the anaesthetic management of a pregnant patient with multiple
      manifestations of HIV infection who underwent Caesarean section. A 30-yr-old, HIV
      positive, Haitian woman presented with acute psychosis at 28 weeks' gestation. A
      diagnosis of HIV dementia complex was made and haloperidol therapy was started.
      Five days after admission the patient was found to be in labour and tocolytic
      therapy with terbutaline was commenced. A vaginal lesion compatible with herpes
      simplex virus was observed which was treated with acyclovir. After 3 days of
      tocolytic therapy there were no further signs of preterm labour. Two weeks later,
      at 30 weeks' gestation, the patient's membranes ruptured spontaneously. The
      herpes labialis lesion was still present and urgent Caesarean section was begun
      using subarachnoid 0.75% bupivacaine 1.5 ml. The patient had no intraoperative
      problems and a 1700-g healthy male child was delivered.

PMID- 7577295
TI  - Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces
      the minimum alveolar anaesthetic concentration of isoflurane in rats.
AB  - We have studied the effect of intrathecal administration of N-methyl-D-aspartate
      (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration
      (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal
      catheters, we determined the MAC of isoflurane after administration of a
      competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 micrograms), a
      non-competitive NMDA receptor antagonist, MK801 (0.1, 1.0, 10, 30 micrograms).
      NMDA (0.01, 0.1, 1.0, 10, 30 micrograms) and saline. APV at all doses except 0.01
      micrograms decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801
      at 10 and 30 micrograms reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001),
      lower doses did not affect MAC. Intrathecal administration of NMDA reversed these
      decreases in MAC, but not to control values with APV 10 and 30 micrograms and
      MK801 30 micrograms. We suspect that NMDA and NMDA receptor antagonists play
      important roles in the spinal cord in determining the MAC of isoflurane.

PMID- 7577297
TI  - Postoperative brachial plexus neuropathy after total knee replacement under
      spinal anaesthesia.
AB  - We describe a case of idiopathic postoperative brachial plexus neuropathy. A 68
      yr-old man underwent elective total knee replacement under spinal anaesthesia.
      Two days after surgery, there was sensory loss and weakness in the right forearm
      and hand, which suggested an ulnar nerve neuropathy. Two weeks later the patient
      complained of a dull ache between the scapulae, followed by a burning sensation
      in the forearm and severe pain in the elbow. A diagnosis of brachial plexus
      neuropathy was made based on clinical examination and nerve conduction studies.
      The pain disappeared after a few months, although weakness of the right arm
      persisted 9 months later. The differential diagnosis between brachial plexus
      neuropathy and ulnar nerve neuropathy is important, as the prognosis of brachial
      plexus neuropathy is generally good.

PMID- 7577299
TI  - NSAID for caesarean section.

PMID- 7577298
TI  - Evaluation of the Pneupac Ventipac portable ventilator: comparison of performance
      in a mechanical lung and anaesthetized patients.
AB  - The performance of the Pneupac Ventipac portable gas-powered ventilator was
      evaluated in two stages. The accuracy of delivery of the ventilator was assessed
      using a mechanical lung model at different combinations of compliance and airway
      resistance to simulate normal and diseased lungs. The performance of the
      ventilator was then assessed in 20 anaesthetized patients. The tidal volume
      delivered by the ventilator in airmix mode (nominal inspiratory oxygen fraction
      (FIO2) 0.45) was between -20 and +30% of the preset tidal volume with the
      mechanical lung model adjusted to normal adult values of compliance and airway
      resistance. The corresponding value with the ventilator set to deliver 100%
      oxygen was between -22 and -7% of the preset tidal volume. The performance of the
      ventilator decreased when either compliance was reduced or airway resistance was
      increased in the mechanical lung model; this effect was greater in airmix mode.
      Delivered tidal volume was between -19 and +12% of the present tidal volume in
      the group of anaesthetized patients using the ventilator in airmix mode. The
      ventilator was reliable and simple to use, and performance was within acceptable
      limits in the anaesthetized patients. However, we recommend that a means of
      verifying the adequacy of ventilation should always be used when transporting
      critically ill or anaesthetized patients with any portable ventilator,
      particularly when lung compliance or airway resistance may be abnormal.

PMID- 7577302
TI  - A subtle cause of circle system failure.

PMID- 7577300
TI  - Removal of lumbar extradural catheters.

PMID- 7577303
TI  - Single medial injection peribulbar anaesthesia.

PMID- 7577301
TI  - Fires and explosions.

PMID- 7577304
TI  - The world of Null-A.

PMID- 7577305
TI  - HIV-related knowledge and risk behaviors of street youth in Belo Horizonte,
      Brazil. The Street Youth Study Group.
AB  - Individual interviews were conducted with 379 youth who work and/or live on the
      streets of a large Brazilian city to assess HIV-related knowledge, sources of
      information, risk behaviors, and prevention beliefs and strategies. Respondents
      demonstrated high levels of factual knowledge about HIV transmission (84%
      correct) coupled with high levels of misconceptions about casual transmission
      (53% correct) and intermediate levels of knowledge about prevention (64%
      correct). Only 54% of the respondents had heard about AIDS recently, and 37.5%
      said they talked to someone about AIDS. The most common sources of information
      about HIV/AIDS were the mass-media and friends. Over half the sample reported
      taking precautions to reduce their risk of HIV infection; however, the proportion
      of youth taking effective precautions was low. Among the 247 youth (65% of the
      sample) who had initiated sexual activity, lifetime condom use was reported by
      18%, and condom use at last intercourse by 10%. Youth with higher levels of
      knowledge were more likely to report behavior changes to avoid HIV infection.
      These findings underscore the urgent need for prevention programs tailored to
      street youth in developing countries.

PMID- 7577306
TI  - The perceived social context of AIDS: study of inner-city sexually transmitted
      disease clinic patients.
AB  - The present study investigated perceptions of AIDS as a social problem relative
      to 10 other problems in a sample of 194 inner-city sexually transmitted disease
      (STD) clinic patients. Within-subjects analyses showed that AIDS was viewed as a
      more serious problem than housing, alcoholism, and child care, while AIDS was
      less of a problem than employment, drug abuse, crime, discrimination, and teen
      pregnancy, and no different from transportation and health care. Factor analysis
      was used to identify the interrelationships among social problems as perceived by
      STD patients. For men, factor analysis showed that AIDS was most closely related
      to crime, drug abuse, teen pregnancy, and discrimination, with these problems
      constituting the first factor and accounting for most of the variance in the
      analysis. Men also placed AIDS with alcoholism and child care on the third factor
      accounting for little variance. For women, however, AIDS clustered most closely
      with alcoholism and child care, accounting for a minimal amount of variance in
      the analysis. Results further showed that perceptions of social problems among
      women correlated with HIV-risk-related behaviors. The structural context of
      social problems, within which AIDS is embedded, is discussed with reference to
      HIV-AIDS-prevention interventions.

PMID- 7577307
TI  - Reducing HIV needle risk behaviors among injection-drug users in the Midwest: an
      evaluation of the efficacy of standard and enhanced interventions.
AB  - This study compares the impact of a standard and an enhanced intervention on the
      needle-use behaviors reported by injection-drug users (IDUs) living in a low
      seroprevalence area in the Midwest. Data on the drug- and needle-use practices of
      381 IDUs completing a standard (n = 232) or an enhanced (n = 149) intervention
      who were followed-up five to nine months after a baseline interview were analyzed
      using bivariate and multivariate techniques. The results indicate that IDUs who
      participated in the enhanced intervention reported safer needle practices than
      standard intervention IDUs at follow-up. In addition, less frequent injectors
      were much more likely to adopt safer needle-use practices than were daily drug
      injectors, regardless of intervention track. The results suggest that more
      intensive interventions have advantages over minimalist efforts--in specific
      contexts. This finding has important implications for the HIV needle risk
      reduction efforts targeting IDUs.

PMID- 7577308
TI  - AIDS prevention with adolescents.
AB  - Prevention of human immunodeficiency virus (HIV) and acquired immunodeficiency
      syndrome (AIDS) among adolescents is increasingly recognized as an important
      public health priority. Sexual risk acts associated with HIV/AIDS transmission
      (unprotected sexual intercourse with multiple partners of unknown serostatus) are
      typically initiated by late adolescence, with many youths engaging in sexual
      relations earlier. Despite being well informed about HIV/AIDS and having positive
      attitudes toward HIV/AIDS prevention, adolescents have not changed their behavior
      in response to the pandemic. AIDS-prevention programs must be tailored to
      consider stereotypic sex roles, gay youths' sexual orientation, and substance
      abuse. Intensive prevention programs focusing on helping youths perceive HIV as a
      problem, motivate them to act safely, and implement safe acts by acquiring coping
      skills, access to condoms and health care, and identifying individual barriers to
      implementing safe acts have successfully reduced adolescents' risk acts. However,
      avenues for broad-scale dissemination of such programs or alternative models to
      change youths' behaviors must be identified.

PMID- 7577310
TI  - HIV/AIDS knowledge among the U.S. population.
AB  - This analysis examines knowledge of HIV and AIDS among 71,370 persons interviewed
      in a national sample of the U.S. population. Factor analysis of 26 questions
      about HIV infection and AIDS identified four distinct dimensions of AIDS
      knowledge: 1) transmission mechanisms; 2) commonly known nontechnical
      information; 3) definitions of AIDS; and 4) technical information. Significant
      differences across racial, ethnic, socioeconomic, and demographic groups exist
      for each dimension of AIDS knowledge. In general, racial minorities and those
      with lower socioeconomic status are shown to have lower knowledge levels.
      Exposure to mass media about AIDS, and knowing a person with HIV or AIDS, are
      also strong predictors of increased knowledge. Multivariate analysis demonstrates
      1) that socioeconomic status is a better predictor of knowledge of AIDS than race
      or ethnicity; and 2) exposure to AIDS mass media has the strongest effect on all
      dimensions of AIDS knowledge except for knowledge of technical issues about AIDS.
      Policy implications of these results are discussed.

PMID- 7577309
TI  - Early childhood differentials in mother-child AIDS-information interaction.
AB  - To date there have been no systematic inquiries into 1) the extent of parent
      child AIDS interaction; or 2) the factors that influence whether young children
      and their parents talk about AIDS. In our sample, from a medium-sized Southern
      metropolitan area, 70 percent of mothers of children in the first, third, and
      fifth grades said they had talked to their child about AIDS, but only 41 percent
      of the mothers said their child had asked them questions about AIDS. Fourteen
      hypotheses about factors which might influence mother-child AIDS interaction are
      derived from the health/sex socialization literature. In the process of testing
      these bivariate hypotheses it is shown that, although sons and daughters are
      equally likely to ask their mother questions about AIDS, mothers are more likely
      to talk to their daughters than their sons about AIDS. This pattern maintains
      even after controls are introduced. It is suggested that discussing AIDS with
      young children as a health issue rather than waiting until adolescence and
      discussing it as a sex issue may be a more effective socialization route. Mothers
      may be able to do this with young daughters in the context of women's health, but
      because most AIDS education for adults generally is sex- rather than health
      oriented they may lack the knowledge and framework to do this with their sons.

PMID- 7577312
TI  - [The determinants of bone mineral density in hemiplegic patients. Preliminary
      data].
AB  - We studied a group of hemiplegic patients to determine the amount of bone loss of
      the paretic versus the normal limb and to evaluate the importance of several
      variables in determining this difference. Thirty consecutive subjects with
      hemiplegia caused by a cerebral vascular accident were studied: 15 postmenopausal
      women (average age 65.1 years) and 15 men (average age 58.3 years) (average age
      of entire group, 63.2 years; age range of entire group, 27-84 years). The mean
      duration of immobilization was 7.7 months for women (range 1-40 months) and 10.5
      months for men (range 1-48 months). All subjects had a complete physical
      examination, underwent bilateral femoral neck DEXA, and filled out a
      questionnaire. The percent difference (delta) between the paretic and normal limb
      was 6.1% in the women and 3.8% in the men. Logistic regression analysis, after
      control for age and sex, indicated that the degree of demineralization depended
      significantly and directly on the duration of immobilization and depended
      inversely on the time elapsed since menopause. Our data evidence the importance
      of immobilization osteoporosis and point to the role of hormonal factors in its
      pathogenesis.

PMID- 7577311
TI  - [The extremely low incidence of proximal femoral fractures due to osteoporosis in
      the population on the island of Ischia].
AB  - We present the raw data from a study done on the incidence of osteoporotic hip
      fractures on Ischia, an island facing the Bay of Naples. Its 43,975 inhabitants
      form a well-defined, stable and homogeneous population. Since no air
      transportation to the mainland is available for residents, acute health care is
      provided by the sole local hospital. We carried out a discharge data survey by
      reviewing the hospital medical records from 1980-1989. During that decade, 148
      residents (111 women, 37 men) had new hip fractures. The age-sex adjusted
      incidence for the population aged 50 years or more was 170.3 cases/100,000/year
      [95% confidence interval (CI) = 144.8-195.9] (women = 241.4 with 95% CI = 211.0
      271.9; men = 79.4 with 95% CI = 62.0-96.9). Age-specific rates increased with age
      and were higher among women only over 60 years old. On the basis of the 1981
      census and comparison of age-adjusted rates, we determined that incidence rates
      of these fractures for men and women on Ischia are among the lowest in the world:
      Ischian men have a hip fracture incidence second only to that of South African
      Bantu males. The female/male ratio on the island, one of the highest reported, is
      3.05:1. Our data suggest that further studies on Ischia may provide important
      clues regarding risk and/or protective factors for hip fracture.

PMID- 7577315
TI  - [ACE inhibitors in the treatment of patients with acute myocardial infarct].
AB  - In this review, we evaluate the efficacy of ACE-inhibitors for the treatment of
      acute myocardial infarction (AMI). Our information is based on published material
      and personal experience derived from extensive revision of the SMILE study. All
      trials with a randomized experimental design, irrespective of their primary
      research objective, have been included. Results are presented in terms of either
      hemodynamic or clinical benefit. The available evidence indicates that the
      mortality rate of AMI patients who undergo short- and long-term treatment with
      ACE-inhibitors is significantly reduced. This reduction is more evident in high
      risk patients, such as subjects with asymptomatic left ventricular dysfunction,
      congestive heart failure on admission, anterior location of the infarction. ACE
      inhibitors also limit the development and progression of congestive heart failure
      after myocardial infarction, the onset of clinical manifestations of coronary
      artery disease (reinfarction, need for revascularization) and the occurrence of
      ventricular arrhythmias, probably by means of mechanisms involving a specific
      effect of these compounds. In conclusion, the available data indicate that
      administration of ACE-inhibitors to patients with AMI is associated with
      significant clinical benefit.

PMID- 7577313
TI  - [Physical training exercise reduces the plasma levels of fibrinogen in subjects
      with mild hypertension].
AB  - We evaluated the behaviour of plasma fibrinogen in subjects undergoing physical
      training in a prospective non-controlled open study, carried out in 14 sedentary,
      mildly hypertensive individuals (mean age 52 +/- 5 years). Subjects underwent 3
      months of controlled physical training (3 times a week) tailored to reach, at
      each session, 80-90% of maximal heart rate based upon a baseline test. Before and
      after the period of training, resting systolic and diastolic blood pressure, 24
      hour systolic and diastolic blood pressure, plasma fibrinogen, body mass index
      (BMI), maximum oxygen consumption (VO2max), serum cholesterol and triglycerides
      were evaluated. After training VO2 max increased (24 +/- 5 vs 30 +/- 5 mL/Kg/min,
      p < 0.01); there were no variations in BMI (24 +/- 2 vs 23 +/- 2 Kg/m2, p =
      0.35), cholesterol (220 +/- 30 vs 213 +/- 36 mg/dL, p = 0.41) or triglycerides
      (117 +/- 51 vs 118 +/- 37 mg/dL, p = 0.58). Resting systolic (148 +/- 10 vs 133
      +/- 10 mmHg, p < 0.01) and diastolic blood pressure (97 +/- 5 vs 85 +/- 6 mmHg, p
      < 0.01) and 24-hour systolic (135 +/- 6 vs 129 +/- 5 mmHg, p < 0.01) and
      diastolic blood pressure (86 +/- 7 vs 81 +/- 6 mmHg, p < 0.01) decreased; plasma
      fibrinogen also decreased (324 +/- 60 vs 278 +/- 53 mg/dL, p < 0.01). Eight
      individuals tested 5 months after cessation of training, showed a return of
      fibrinogen, blood pressure and VO2 max to baseline values.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7577314
TI  - [Allelic variations of DPB1, DQA1, DQB1 and DRB1 and rheumatoid arthritis:
      further genetic and statistical considerations].
AB  - We used polymerase chain reaction amplification and hybridization with specific
      oligonucleotides to analyze the distribution of DPB1, DQA1, DQB1, and DRB1
      allelic variants in 48 patients with rheumatoid arthritis (RA) and compared our
      results with those from 109 randomly chosen, healthy control subjects. Our work
      confirms a previously reported increase in DR4 specificity in RA: in particular,
      we found a statistically significant positive association of the DRB1*0401 and
      DRB1*0404 alleles with RA. When we compared the DR4 groups, however, none of the
      DRB1*04 alleles were increased in the RA group. Molecular analysis of the other
      DRB1 polymorphic variants disclosed the trend of a positive association of
      DRB1*0101 (DR1) in DR4 negative patients vs DR4 negative healthy control
      subjects, and an increase in DRw6 (DRB1*13,*14) in the DR4 and/or DR1 negative
      patient group. Moreover, analysis of the association between RA and a
      heptapeptide motif (positions 67-74) in the third hypervariable region confirmed
      that this epitope confers enhanced risk for the development of RA with respect to
      the allele DRB1*0404 (etiologic fraction = 0.53 vs 0.12). We also observed a
      statistically significant increase in DQA1*0301 and DQB1*0302 accompanied by a
      significant decrease in DQA1*0202, DQA1*0501 and DQB1*0201 in RA patients.
      Analysis of DPB1 alleles disclosed no significant differences between RA patients
      and healthy control subjects.

PMID- 7577316
TI  - [Idiopathic CD4+ lymphocytopenia: a case report].
AB  - We present the case of a 47-year-old patient who was seen for recurrent
      opportunistic infections. Immunophenotypic analyses disclosed severe reduction of
      CD4+ T cells. Repeated Elisa, Western blot and polymerase chain reaction tests
      for HIV were negative. The low CD4+ T lymphocyte count unaccompanied by increased
      CD8+ T lymphocytes and hypergammaglobulinemia, along with negativity for HIV
      infection, suggested the diagnosis of idiopathic CD4+ lymphocytopenia (ICL). The
      patient's clinical manifestations and laboratory results conformed with the case
      definition of ICL established in 1992 by the Centers for Disease Control of
      Atlanta, i.e., CD4+ T cells < 300/mm3 on two occasions and no evidence of HIV
      infection. In vitro analyses evidenced depressed lymphoproliferative responses to
      mitogens such as concanavalin A and pokeweed mitogen, while the expression of Fas
      antigen on peripheral lymphocytes and the percentage of apoptotic cells after
      propidium iodide staining were increased. Since in vitro concanavalin A
      stimulation inhibits T cell proliferation and induces apoptosis, these results
      suggest that the patient's lymphocytes are susceptible, in vivo, to an apoptotic
      signal.

PMID- 7577317
TI  - Interferon or hepatitis C virus induced autoimmune aplastic anemia and severe
      thrombocytopenia? A case report.
AB  - We describe a case of aplastic anemia with severe thrombocytopenia in a patient
      affected by chronic active hepatitis C treated with interferon. The hematologic
      alterations did not disappear after suspension of interferon or after the ensuing
      steroid treatment. Administration of cyclosporin markedly improved the
      hematologic parameters and serum transaminase levels.

PMID- 7577318
TI  - Effect of selenium on malignant tumor cells of brain.
AB  - Some reports have demonstrated that selenium can inhibit tumorigenesis in some
      tissues of animal. However, little is known about the inhibitory effect on
      malignant tumor cells of brain. The purpose of our study was to determine the
      biological effect of selenium on growth of rat glioma and human glioblastoma cell
      lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research
      Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified
      Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a
      humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium
      were evaluated using growth rate assay quantifying cell number by MTT assay. An
      antiproliferative effect of selenium was found in two cell lines, which was more
      effective on human A172 glioblastoma and less effective on rat C6 glioma.

PMID- 7577319
TI  - Mitochondrial selenium-75 uptake and regulation revealed by kinetic analysis.
AB  - Uptake of Na2(75)SeO3 by mitochondria of the larvae of the insect C. cephalonica
      reared at different dietary selenium (Se) levels revealed: 1. A proportional
      increase in the uptake with externally added Na2(75)SeO3 in concentrations upto
      25.32 microM; and 2. At each added selenite concentration, an increase up to 60
      min, with linearity up to 15-30 min. A differential affinity for Na2(75)SeO3 was
      elicited in the mitochondrial protein fractions of different dietary Se groups
      and correlated well with the pattern and the ratio of distribution of
      incorporated 75Se in protein to nonprotein fractions. Kinetic studies on 75Se
      uptake by whole mitochondria negated passive diffusion of selenite and revealed a
      trend of negative cooperativity, confirmed by Hill and Scatchard plots. Half
      saturation value was estimated to be approx 13 nmole Se/mg mitochondrial protein.
      Scatchard plot for 75Se uptake was biphasic and the high affinity binding sites
      were estimated to be around 5 nmole/mg mitochondrial protein. Calculated
      dissociation constants revealed maximal affinity for 75Se in the 1.5 ppm group
      (KSe 0.0034 nM) and minimal in the basal group (KSe 0.007 nM). In the
      mitochondria of all the three dietary Se groups, the estimated low affinity sites
      amounted to be 15-19 nmole/mg mitochondrial protein. Inherent Se in the
      mitochondria of the high Se group positively enhanced the incorporation of 75Se
      in the mitochondrial protein fraction. About 20-30% of the total uptake was
      indicated to be energy linked as revealed by studies with respiratory inhibitors.
      Addition of sulfite and sulfate (5-25 microM) in the medium, inhibited 75Se
      uptake by 35-55%, suggestive of the involvement of the dicarboxylate port. Thiol
      interactive 75Se uptake was confirmed by the inhibition mediated by mersalyl and
      NEM up to 50-70%. The study revealed thiol-selenite interactions of metabolic
      significance during selenite uptake.

PMID- 7577320
TI  - Distribution of various nickel compounds in rat organs after oral administration.
AB  - In this study, eight kinds of nickel (Ni) compounds were orally administered to
      Wistar male rats and the distribution of each compound was investigated 24 h
      after the administration. The Ni compounds used in this experiment were nickel
      metal [Ni-M], nickel oxide (green) [NiO(G)], nickel oxide (black) [NiO(B)],
      nickel subsulfide [Ni3S2], nickel sulfide [NiS], nickel sulfate [NiSO4], nickel
      chloride [NiCl2], and nickel nitrate [Ni(NO3)2]. The solubilities of the nickel
      compounds in saline solution were in the following order; [Ni(NO3)2 > NiCl2 >
      NiSO4] >> [NiS > Ni3S2] > [NiO(B) > Ni-M > NiO(G)]. The Ni level in the visceral
      organs was higher in the rats given soluble Ni compounds; Ni(NO3)2, NiCl2, NiSO4,
      than that in the rats receiving other compounds. In the rats to which soluble Ni
      compounds were administered, 80-90% of the recovered Ni amounts in the examined
      organs was detected in the kidneys. On the other hand, the Ni concentration in
      organs administered scarcely soluble Ni compounds; NiO(B), NiO(G), and Ni-M were
      very low. The estimated absorbed fraction of each Ni compounds was increased with
      the increase of the solubility. These results suggest that the kinetic behavior
      of Ni compounds administered orally is closely related with the solubility of Ni
      compounds, and that the solubility of Ni compounds is one of the important
      factors for determining the health effect of Ni compounds.

PMID- 7577322
TI  - Accumulation of hydroxyapatite in the kidney of streptozotocin-induced diabetic
      rat fed a low-zinc diet.
AB  - Calcification occurred in the kidney of streptozotocin (STZ)-induced diabetic
      rats fed a low-zinc diet. The deposits were stained by the von Kossa method and
      were detected intracellularly in the tubular cells, mainly in the cortico
      medullar region. The deposits were found to be a heterogenous substance on
      electron microscopy. There were various sizes of deposits, and the surfactant was
      very much distorted. Many deposits grew up to bind small particles, and the core
      like substance was observed in the center of the deposit. The component of the
      deposit was analyzed by an X-ray microanalyzer, and was found to be calcium and
      phosphorus. The ratio of calcium to phosphorus was 2.159, which coincided with
      the ratio of standard hydroxyapatite. From these observations, the deposit is
      believed to be hydroxyapatite. It is thought that the core is formed at first,
      many particles are then bound to the core, and deposits grow up.

PMID- 7577321
TI  - Zinc and manganese bioavailability from human milk and infant formula used for
      very low birthweight infants, evaluated in a rat pup model.
AB  - The bioavailability of zinc and manganese from diets used for very low
      birthweight infants was investigated in a rat pup model using radioisotopes. The
      effect of protein source and content and of pasteurization was evaluated, and two
      different approaches for evaluation of zinc and manganese bioavailability from
      the studied human milk and infant formula for very low birthweight infants was
      high. Liver uptake of 65Zn from labeled premature infant diets in sucklings rat
      pups was 26-29%, and absorption calculated as the difference between administered
      dose and nonabsorbed activity 6 h after oral intubation was 93-95%. Retention of
      manganese calculated as the sum of 54Mn retained by organs and carcass was 85-95%
      from human milk and premature infant formula, and absorption calculated from
      nonabsorbed activity was 83-88% after 6 h. Fortification of early human milk
      significantly increased the bioavailability of zinc. No effect of pasteurization
      of human milk was found on zinc or manganese bioavailability. Liver zinc uptake
      was found to be a more sensitive parameter than absorption for evaluation of
      diets with a high zinc bioavailability. Measurement of retained activity of
      manganese in carcass and organs was judged to be the preferred parameter for
      evaluation of diets with high manganese availability.

PMID- 7577323
TI  - Iron, zinc, and copper levels in different tissues of clinically vitamin A
      deficient rats.
AB  - To clarify the effect of vitamin A deficiency on iron, zinc, and copper status in
      different tissues, three groups of rats were fed two types of synthetic diets for
      52 d. Group one, which was fed a vitamin A-deficient diet, showed severe signs of
      vitamin A deficiency. Groups two (fed restricted amount, pair-fed with group
      one), and three (fed diet ad libitum) were fed a control diet. After said period
      of feeding, iron, zinc, and copper were measured in different tissues.
      Significant changes observed when the groups were compared are summarized below:
      1. Iron and copper in testes were increased significantly, whereas zinc was
      strikingly decreased in group one when compared with the other groups; 2. Copper
      (in lung and kidney) and iron (in the spleen) were increased significantly in
      group one compared with the other groups; 3. In the liver, iron, zinc, and copper
      were significantly different between group one and group two; 4. In muscle, iron
      was significantly higher in group one than group two; 5. In tibia and blood, iron
      levels (but not zinc and copper) in groups one and two were significantly higher
      than group three. These results suggest that vitamin A deficiency affects iron,
      zinc, and copper status in rats.

PMID- 7577324
TI  - Different tissue responses for iodine and iodide in rat thyroid and mammary
      glands.
AB  - This research describes the effects of short-term elemental iodine (I2) and
      iodide (I-) replacement on thyroid glands and mammary glands of iodine-deficient
      (ID) Sprague-Dawley female rats. Iodine deficiency causes atypical tissue and
      physiologic changes in both glands. Tissue histopathology and the endocrine
      metabolic parameters, such as serum TT4, tissue and body weights, and vaginal
      smears, are compared. A moderate reduction in thyroid size from the ID control
      (IDC) was noted with both I- and I2, whereas serum total thyroxine approached the
      normal control with both I- and I2, but was lower in IDC. Thyroid gland IDC
      hyperplasia was reduced modestly with I2, but eliminated with I-. Lobular
      hyperplasia of the mammary glands decreased with I2 and increased with I- when
      compared with the IDC; extraductal secretions remained the same as IDC with I2,
      but increased with I-; and periductal fibrosis was markedly reduced with I2, but
      remained severe with I-. Thus, orally administered I2 or I- in trace doses with
      similar iodine availability caused different histopathological and endocrine
      patterns in thyroid and mammary glands of ID rats. The significance of this is
      that replacement therapy with various forms of iodine are tissue-specific.

PMID- 7577325
TI  - The separation of overlapping neuromagnetic sources in first and second
      somatosensory cortices.
AB  - In response to a somatosensory stimulus, two cortical centers in each hemisphere
      produce neural mass activity large enough to be detected with electric (EEG) or
      magnetic (MEG) measurements. Both the primary somatosensory cortex (S-I), located
      in the postcentral sulcus and in the depths of the central sulcus, as well as the
      secondary somatic sensory cortex (S-II), lying in the upper bank of the Sylvian
      fissure, respond within the first 100 ms such that the two activities overlap in
      time. We demonstrate that this overlap can be disentangled using a MUSIC-type
      approach, as suggested by Oppelt and Scholz. It needs no a priori information
      about the sources. As the results show, there are several instances in time in
      which only one of the two centers (SI, SII) is active. It is only for these time
      segments that a single moving dipole yields meaningful results. Such time
      intervals occur during the upstroke of the late component around 60 ms (only SI
      activity) and during the down-stroke around 120 ms (only SII activity). In these
      time intervals the activity of one of the somatosensory areas is still large
      enough, while the other center is not yet or is no longer active.

PMID- 7577326
TI  - Functional localization based on measurements with a whole-head magnetometer
      system.
AB  - Whole-cortex magnetometers represent a significant methodological breakthrough in
      noninvasive studies of the brain's electrical activity. This paper describes our
      122-channel instrument with planar gradiometers, methods to interpret its data,
      and gives a few examples of neuromagnetic studies.

PMID- 7577327
TI  - Neuromagnetic source analysis using magnetic resonance images for the
      construction of source and volume conductor model.
AB  - Sources of the somatosensory evoked fields (SEF) for one subject were estimated
      using constraints from the magnetic resonance images (MRI) of the same subject. A
      realistic volume conductor model was shaped corresponding to the inside of the
      skull. Sources were restricted to a dipole patch riding on the surface of the
      cortex, reconstructed from the individual MRI. Such a patch can be considered as
      a uniformly activated cortical area giving rise to distributed currents which
      flow perpendicular to the cortical surface. Source locations obtained for the SEF
      in response to separate stimulations of lower lip, first and fifth digit, and
      collarbone followed the course of the contralateral central sulcus. The order of
      the estimated source locations was in agreement with the somatosensory homunculus
      of Penfield and Rasmussen. Similar results were obtained with the simple model of
      a current dipole in a homogeneous sphere. In contrast, combining a current dipole
      model with a realistic volume conductor model was rather problematic as it
      overestimates the radial dipole component by an order of magnitude.

PMID- 7577328
TI  - Exploring memory functions by means of brain electrical topography: a review.
AB  - A series of experiments is reviewed which explored whether the functional brain
      state of long-term memory retrieval is correlated with specific changes in slow,
      DC-like event-related brain potentials. The main results are: (1) Retrieving
      associations from long-term memory is accompanied by a slow negative shift of 5
      10 microV which prevails about as long as the retrieval process lasts, i.e., in
      our experiments, for a period of several seconds: (2) When different types of
      representations have to be reactivated in memory the slow negative wave shows a
      clearly distinct topography. The maximum was found in a verbal condition over the
      left frontal, in a spatial condition over the parietal, and in a color condition
      over the right occipital to temporal cortex. All these conditions were completely
      equivalent with respect to the established associative structure, the learning
      procedure, and the performance criterion. (3) The amplitude of the topographic
      maximum increases with the number of representations which have to be
      reactivated. This effect is not due to a non-specific increase of effort but
      specifically related to the number of activated episodic memory contents which
      had been experimentally established. In contrast, the reactivation of a priori
      given semantic association did not become manifest in a specific slow wave
      effect. These findings are compatible with the idea that memory retrieval implies
      a reactivation of those cortical cell assemblies in the cortex in which the
      constituting features of a mnestic entity had originally been processed during
      perception and learning. The results are also discussed with respect to the
      possible advantages of EEG and MEG recordings for a cognitive psychophysiology in
      comparison to other brain imaging techniques as PET or fMRI.

PMID- 7577330
TI  - Evoked and induced gamma-band activity of the human cortex.
AB  - The evoked gamma-band activity is an event related rhythmic response which
      persists within the first 100 ms after the stimulus onset. It shows spectral
      peaks between 30 and 40 Hz in the auditory, between 45 and 55 Hz in the
      somatosensory and between 100 and 110 Hz in the visual system. After separation
      of the wide-band activity in slow and gamma-band activity, a moving single
      equivalent current dipole model accounts for each activity almost completely. The
      induced gamma-band activity is not phase-locked to the stimulus or it is strongly
      gittering and thus it cannot be extracted in time domain. In this case we are
      using signal analysis methods in frequency domain. The evaluation of the induced
      brain gamma-band activity around 30 Hz shows differences to word and nonword
      stimuli. It was supposed that the induced gamma-band activity represents the
      synchronized activity of Hebbian cell assemblies correlated to words.

PMID- 7577331
TI  - 5th International Symposium of the International Society for Brain
      Electromagnetic Topography. Munster, Germany, August 2-6, 1994. Abstracts.

PMID- 7577332
TI  - Marrow transplantation for chronic myeloid leukemia.

PMID- 7577329
TI  - Generators of electrical and magnetic mismatch responses in humans.
AB  - Studies bearing on generators of the electric and magnetic mismatch responses in
      humans to change in a repetitive sound are reviewed. It was concluded that the
      main contribution of the mismatch negativity (MMN) and of its magnetic equivalent
      MMNm, elicited even in the absence of attention, originates from auditory cortex
      on the supratemporal plane. In addition, those responses probably have one or two
      sources on the right lateral temporal cortex and, at least the MMN, a source also
      in the right frontal cortex. The activation caused by stimulus change in the
      sensory-specific cortex is, presumably, a manifestation of preperceptual change
      detection, whereas the frontal activation might be associated with conscious
      perception of, attention switch to, stimulus change.

PMID- 7577334
TI  - Peripheral blood stem cell transplantation.

PMID- 7577333
TI  - Marrow transplantation from unrelated volunteer donors.

PMID- 7577335
TI  - Umbilical cord blood stem cell transplantation.

PMID- 7577336
TI  - In vitro expansion of hematopoietic cells for clinical application.

PMID- 7577337
TI  - Recombinant hematopoietic growth factors in bone marrow transplantation.

PMID- 7577339
TI  - Genetic therapy using bone marrow transplantation.

PMID- 7577340
TI  - Myeloablative radiolabeled antibody therapy with autologous bone marrow
      transplantation for relapsed B cell lymphomas.

PMID- 7577338
TI  - Detection of minimal residual disease.

PMID- 7577341
TI  - Graft versus leukemia in humans.

PMID- 7577342
TI  - Interleukin-2 in bone marrow transplantation.

PMID- 7577343
TI  - Cellular adoptive immunotherapy after bone marrow transplantation.

PMID- 7577346
TI  - Bone marrow transplantation for metabolic diseases.

PMID- 7577344
TI  - Bone marrow transplantation in thalassemia.

PMID- 7577347
TI  - Cytomegalovirus infection in marrow transplantation.

PMID- 7577345
TI  - High-dose chemotherapy and autologous stem cell transplantation for breast
      cancer.

PMID- 7577349
TI  - Rapid chiral separation methods development by cyclodextrin-mediated capillary
      electrophoresis for acidic and basic compounds.
AB  - Chiral separation methods development using conventional techniques such as GC or
      HPLC requires a lot of experience, effort, and expense, due to the wide diversity
      of the optically active solutes and their possible chiral selectors. Capillary
      electrophoresis has received increased attention as an alternative technique for
      chiral separation due to its inherent high efficiencies and ease of methods
      development. However, due to the wide variety of chiral selectors available in
      CE, the benefits of this technique might be diminished without an appropriate
      methods development scheme. In this paper detailed examples are shown for fast,
      efficient, and predictable chiral capillary electrophoresis separation methods
      development based on a new and systematic theory. Optimized separations and their
      parameters are presented for several enantiomeric acids and bases. All the three
      possible cases, such as the use of low and high pH, as well as pH = pK buffer
      systems are thoroughly discussed.

PMID- 7577348
TI  - Determination of the enantiomers of citalopram, its demethylated and propionic
      acid metabolites in human plasma by chiral HPLC.
AB  - A stereoselective HPLC assay has been developed to analyze the enantiomers of
      citalopram and of its three main metabolites in plasma after their separation on
      a Chiracel OD column. Using a fluorescence detector, the limit of quantification
      in plasma samples was 15, 4, 5 and 2 ng/ml for the enantiomers of citalopram
      (CIT), desmethylcitalopram (DCIT), didesmethylcitalopram (DDCIT), and for the
      citalopram propionic acid derivative (CIT-PROP), respectively. Except for CIT,
      all metabolites were derivatized with achiral reagents. Identification of the
      enantiomers was realized with an optical rotation detector which showed that the
      enantiomers invert their rotation depending on the polarity and nature of the
      solvent. Under varying conditions, a racemization study has shown that the pure
      enantiomers of CIT and its demethylated metabolites are configurationally stable.
      Preliminary results obtained with five patients treated with CIT show a mean S/R
      ratio of 0.7 for both CIT and its active metabolite DCIT and of 3.6 for CIT-PROP
      in plasma. This suggests that the pharmacologically relevant (+)-(S)-isomers of
      CIT and DCIT could be preferentially and stereoselectively metabolized to CIT
      PROP.

PMID- 7577350
TI  - GABAA agonists: resolution and pharmacology of (+)- and (-)-isoguvacine oxide.
AB  - (3SR,4RS)-3,4-Epoxypiperidine-4-carboxylic acid (isoguvacine oxide) is a potent
      and specific GABAA receptor agonist. Isoguvacine oxide, originally designed as a
      potentially alkylating agonist, turned out to interact with the GABAA receptor in
      a fully reversible manner. The protected form of isoguvacine oxide, benzyl
      (3SR,4RS)-1-(benzyl-oxycarbonyl)-3,4-epoxypiperidin e-4-carboxylate (1) (Scheme
      1), has now been resolved by chiral chromatography using cellulose triacetate as
      a chiral stationary phase. The enantiomers of 1 (ee > or = 98.8%) were
      subsequently deprotected by hydrogenolysis. Whereas both enantiomers of
      isoguvacine oxide were inactive as inhibitors of the binding of [3H]GABA to GABAB
      receptor sites (IC50 > 100 microM), (+)-isoguvacine oxide (IC50 = 0.20 +/- 0.03
      microM) and (-)-isoguvacine oxide (IC50 = 0.32 +/- 0.05 microM) showed comparable
      potencies as inhibitors of the binding of [3H]GABA to GABAA receptor sites.
      Furthermore, (+)-isoguvacine oxide (EC50 = 6 microM; 33% relative efficacy) and (
      )-isoguvacine oxide (EC50 = 5 microM; 38% efficacy relative to 10 microM
      muscimol) were approximately equipotent and equiefficacious as stimulators of the
      binding of [3H]diazepam to the GABAA receptor-associated benzodiazepine site.
      This latter effect is an in vitro estimate of GABAA agonist efficacy. These
      pharmacological data for isoguvacine oxide and its enantiomers do not seem to
      support our earlier conception of the topography of the GABAA recognition
      site(s), derived from extensive structure-activity studies on GABAA
      agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577351
TI  - Circular dichroism of ketoprofen complexed to serum albumins: conformational
      selection by the protein: a novel optical purity determination technique.
AB  - Complexation of 2-(3'-benzoylphenyl)propionic acid (ketoprofen), 1, to bovine
      serum albumin (BSA) results in an intense negative circular dichroism in the
      ketonic n-->pi* band of the benzoylphenyl moiety. This high CD contrasts with the
      weak CD of 1-enantiomers dissolved in common solvents. Furthermore, a number of
      chiral and achiral molecules containing the benzophenone moiety are easily
      complexed to BSA: all these complexes show an intense CD at the same transition.
      To account for the observed CD intensities of the above molecules, it appears
      that BSA complexation markedly shifts the equilibrium between strongly
      asymmetric, antipodic conformers. Dissymmetry of these conformers is connected to
      the instability of a structure with phenyl rings coplanar to the carbonyl
      chromophore, as also indicated by molecular mechanics calculations. The
      magnification of the Cotton effects of the 1-antipodes, due to the protein, can
      be used to measure the optical purity of 1-samples with excellent precision. In
      contrast with BSA, human SA is unable to recognize the chirality of 1-antipodes;
      oleic acid cocomplexation modifies this fact as well as other features of the
      binding.

PMID- 7577352
TI  - Synthesis of (+)-(R)- and (-)-(S)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'
      propenyl)] aminotetralin: new 5-HT1A receptor ligands.
AB  - (R,S)-trans-8-Hydroxy-2-[N-n-propyl-N-(3'-iodo-2'- propenyl)amino]tetralin 7, a
      new radioiodinated ligand based on 8-OH-DPAT, was reported as a potential ligand
      for 5-HT1A receptors. The optically active (+)-(R)- and (-)-(S)-7 were prepared
      to investigate the stereoselectivity of (R,S)-7. Racemic intermediate 8-methoxy-2
      N-n-propyltetralin was reacted with the acyl chloride of (-)-(R)-O-methylmandelic
      acid to form a mixture of (S,R)- and (R,R)-diastereoisomers, which were separated
      by flash column chromatography. After removing the N-acyl group from the
      diastereoisomers, the desired (+)-(R)- or (-)-(S)-7 was obtained by adding an N
      iodopropenyl group. In vitro homogenate binding studies showed the
      stereoselectivity of this new compound for 5-HT1A receptors. (+)-(R)-7 isomer
      displayed 100-fold higher affinity than the (-)-(S)-7 isomer. Biochemical study
      indicated that (+)-(R)-7 potently inhibited forskolin-stimulated adenylyl cyclase
      activity in hippocampal membranes (Emax and EC50 were 24.5% and 5.4 nM,
      respectively), while (-)-(S)-7 showed no effect at 1 microM. The radioiodinated
      (+)-(R)- and (-)-(S)-[125I]7 were confirmed by coelution with the resolved
      unlabeled compound on HPLC (reverse phase column PRP-1, acetonitrile/pH 7.0
      buffer, 80/20). The active isomer, (+)-(R)-[125I]7, displayed high binding
      affinity to 5-HT1A receptors (Kd = 0.09 +/- 0.02 nM). In contrast, the (-)-(S)-7
      isomer displayed a significantly lower affinity to the 5-HT1A receptor (Kd > 10
      nM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577353
TI  - Partial characterisation of pediocin PO2 and comparison with nisin for
      biopreservation of meat products.
AB  - A plasmid associated bacteriocin (pediocin PO2) was isolated by ammonium sulphate
      precipitation from cell-free growth media and subsequent studies showed that the
      partially purified pediocin PO2 was most likely identical (molecular mass
      approximately 3200 daltons in size by SDS-PAGE, stable to low pH and heat at 121
      degrees C for 15 min, inactivated by various proteolytic enzymes and resistant to
      treatment with a range of solvents, except 10% formaldehyde) to other pediocins
      (PA-1 and AcH) previously reported. The antagonistic spectrum of activity of
      pediocin PO2 was compared with nisin and showed a narrower host-range, but a much
      greater activity against Listeria species including strains of Listeria
      monocytogences, than did nisin. A rapid method of reflectance colorimetry was
      used to quantitate growth and acid production (as determined by the colour change
      in bromcresol purple) of Lactobacillus curvatus, added to a meat product model
      system. The combined effects of refrigeration temperature, microbial load and
      bacteriocin concentration were determined in the model over 15 days storage. Both
      nisin and pediocin demonstrated inhibitory activity against Lactobacillus
      curvatus in the model system. However, when bacteriocins were incorporated into a
      manufactured cooked meat product only low nisin activity and no pediocin activity
      was detected, after challenge of vacuum packaged slices of product with
      Lactobacillus curvatus, over a 21 day storage trial under refrigeration
      temperatures.

PMID- 7577354
TI  - Influence of culture conditions on biofilm formation by Escherichia coli O157:H7.
AB  - Biofilms of Escherichia coli O157:H7 were developed on stainless steel chips in
      trypticase soy broth (TSB), 1/5 dilution of TSB, 0.1% Bacto peptone (BP) and a
      minimal salts medium (MSM) supplemented with 0.04% of one of the following carbon
      sources: glucose, glycerol, lactose, mannose, succinic acid, sodium pyruvate or
      lactic acid. It was found that biofilms developed faster and a higher number of
      adherent cells (ca. 10(6) CFU/cm2) were recovered when the organisms were grown
      in the low nutrient media. Regardless of the carbon source, biofilms developed in
      MSM consisted of shorter bacterial cells and thicker extracellular matrix (ECM),
      with glucose as the best substrate for stable biofilm formation. Fewer bacteria
      in initial attachment, non-hydrophobicity of bacterial cells, lack of ECM
      formation and easy detachment of the biofilm bacteria may contribute to poor
      biofilm formation in TSB. ECM is probably important for the stability of
      biofilms; however, at 10 degrees C and under anaerobic conditions, ECM seems to
      be unnecessary.

PMID- 7577356
TI  - Factors affecting results obtained with European Community tests for pasteurized
      milk sampled at the heat treatment establishment.
AB  - A total of 3000 samples of pasteurized milk taken at the heat treatment
      establishment over a 1-year period were examined for the presence of phosphatase
      and by a plate count at 30 degrees C, a coliform count at 30 degrees C, and a
      plate count at 21 degrees C after pre-incubation of the sample for 5 days at 6
      degrees C, performed as prescribed in EC Directive 85/397/EEC. Samples were also
      examined for presence of Listeria species. Of 2690 samples (1713 from small
      dairies and 977 from large commercial premises) received at 4 degrees C or less,
      96 (3.6%) has a plate count at 30 degrees C exceeding 30,000 organisms per ml,
      608 (22.6%) contained 1 or more coliforms per ml, and in 1327 (49.3%) the pre
      incubated count exceeded 100,000 organisms per ml. Thirty two samples from 23
      dairies contained phosphatase. Listeria species were detected in 25 samples; only
      three of these strains were identified as Listeria monocytogenes. Results were
      analysed to determine relationships between factors which might affect test
      results. Samples from small dairies showed significantly higher coliform counts
      and pre-incubated plate counts than did those from large commercial premises.
      They were also more likely to contain phosphatase or Listeria species. Samples
      were significantly more likely to contain coliforms when taken in the July
      September quarter or if received in glass containers.

PMID- 7577355
TI  - Enrichment in Fraser broth supplemented with catalase or Oxyrase, combined with
      the microcolony immunoblot technique, for detecting heat-injured Listeria
      monocytogenes in foods.
AB  - The microcolony immunoblot technique using monoclonal antibodies to Listeria
      monocytogenes was evaluated for its suitability to detect heat-injured cells.
      Pasteurized milk and filtrates of homogenized raw ground beef slurry and cabbage
      were inoculated with L. monocytogenes Scott A, heated, diluted, inoculated into
      Fraser broth (FB) supplemented with 400 micrograms of catalase ml-1 or 0.01 unit
      of Oxyrase ml-1, and incubated at 30 degrees C for 6 h. Three inoculum
      populations (high, medium, and low) were used. The extent of injury was dependent
      on the heating menstruum. Forty percent of the cells were injured in beef slurry
      filtrate, whereas 79 and 94% were injured in milk and cabbage filtrate,
      respectively, when foods were heated at 52 degrees C for 20 min. Populations of
      viable cells were determined using the immunoblot technique and by surface
      plating on modified Oxford (mMOX) agar. Recovery of cells from heated foods was
      enhanced in FB supplemented with catalase or Oxyrase compared to recovery in
      control broth. Essentially all unheated (control) cells could be detected within
      about 30 h using enrichment and the immunoblot technique; 54 h were required to
      easily detect colonies on mMOX. In most cases, the number of cells detected in
      heated milk or filtrates of homogenized beef after enrichment in FB supplemented
      with catalase or Oxyrase was significantly higher than populations detected using
      unsupplemented FB; however, enrichment in FB supplemented with catalase or
      Oxyrase did not significantly increase cell populations in heated cabbage
      filtrate. Within each heat treatment and level of inoculum, cell populations
      detected on mMOX agar after incubating plates for 48 h or on immunoblots after 24
      h were not significantly different. Results indicate that the immunoblot
      technique in conjunction with enrichment in FB containing either catalase or
      Oxyrase can be successfully used to detect healthy and heat-injured cells of L.
      monocytogenes in diverse types of foods within 34 h.

PMID- 7577357
TI  - Identification of Enterococcus species isolated from foods of animal origin.
AB  - Enterococci isolated from a large variety of fresh and prepared foods of animal
      origin during routine microbiologic control tests in a distribution firm, were
      identified to species level using API 20 STREP galleries supplemented with
      conventional tests, rapid ID32 STREP galleries and SDS-PAGE analysis. API 20
      STREP tests correctly identified 77% of the strains, mainly Enterococcus faecium
      and E. faecalis. A simple presumptive identification scheme based on
      pigmentation, tetrazolium reduction and acid production from mannitol and
      raffinose identified 90% of the strains. More complex procedures were necessary
      to identify the remaining strains. Nearly all strains isolated from hard cheeses
      and prepared cheese-meat combinations were identified as E. faecium while E.
      faecalis was the most frequent species in crustaceans. In meat and in prepared
      meat products E. faecium, E. faecalis and less frequently E. hirae/E. durans were
      found. Three of four E. gallinarum strains were isolated from products containing
      turkey meat.

PMID- 7577358
TI  - Mathematics of predictive food microbiology.
AB  - Commonly encountered problems related to modelling bacterial growth in food are
      analysed from a mathematical point of view. Modelling techniques and terms, some
      misused, are discussed and an attempt is made to clarify how, and under what
      conditions, they may be used. A theoretical framework is given to provide a basis
      in which mathematical models having been used in predictive microbiology can be
      embedded. By using several simplifying idealizations as a compromise between the
      complexity of the biological system and the available data, a practically usable
      model becomes available.

PMID- 7577359
TI  - Degradation of sinigrin by Lactobacillus agilis strain R16.
AB  - Forty-two lactobacilli were screened for their potential to degrade glucosinolate
      sinigrin. One of them, strain R16, demonstrated a high level of sinigrin
      degradation; it was identified as Lactobacillus agilis. The sinigrin degrading
      activity of L. agilis R16 could only be demonstrated when intact cells were used.
      The products of sinigrin degradation are allyl-isothiocyanate (AITC) and glucose
      (which is further fermented to DL-lactic acid), suggesting that myrosinase
      activity is involved. The activity was induced by the presence of sinigrin.
      Glucose inhibited the myrosinase activity, even in induced cells. Lactobacillus
      agilis R16 was able to grow on an extract of brown mustard seed and caused
      glucosinolate degradation.

PMID- 7577361
TI  - Occurrence of Listeria monocytogenes in soft and semi-soft cheeses in retail
      outlets in Sweden.
AB  - Samples of 333 retail cheeses produced in or imported into Sweden were examined
      for the presence of Listeria monocytogenes. Listeria monocytogenes was isolated
      from 6% of the cheese samples. Cheeses made from raw milk were more frequently
      contaminated with L. monocytogenes (42%) than cheeses made from heat-treated milk
      (2%). The incidence of the organism in whole cheeses and pre-cut wedges was
      similar (6%). L. monocytogenes was only found in imported cheeses (18 from
      France, and one from Germany and Italy, respectively). The numbers of L.
      monocytogenes varied from < 1 x 10(2) to 1 x 10(5) cfu/g. All L. monocytogenes
      strains belonged to serogroup 1/2, except isolates from two samples that belonged
      to serogroup 4.

PMID- 7577360
TI  - Effect of growth of selected lactic acid bacteria on storage life of beef stored
      under vacuum and in air.
AB  - The effect of growth of different types of lactic acid bacteria (LAB) on the
      storage life of normal pH beef was determined anaerobically (under vacuum) and
      aerobically. Four LAB from meat were inoculated separately onto sterile slices of
      lean beef. Inoculated samples were stored anaerobically at 2 degrees C for 10
      weeks or stored aerobically in an oxygen permeable film at 7 degrees C for 10
      days, with and without previous storage under vacuum at 2 degrees C. The LAB
      strains used were Carnobacterium maltaromicus (previously C. piscicola) LV17 and
      UAL26, Leuconostoc gelidum UAL187-22 and Lactobacillus sake Lb706. Storage life
      was determined by sensory panel evaluation of colour and odour. Under anaerobic
      conditions Lb. sake Lb706, inoculated at log 2 CFU/cm2, grew rapidly to reach
      maximum population within three weeks of storage. L. gelidum UAL187-22 also grew
      on the meat but at a slower rate. In contrast, growth of C. maltaromicus LV17 and
      UAL26 was unpredictable, achieving maximum population after 2 to 8 weeks. None of
      the test strains caused spoilage of the meat within the 10-week storage period
      under vacuum. When the test organisms were inoculated at an initial level of log
      4 CFU/cm2, C. maltaromicus LV17 and UAL26 produced off-odours after 8 weeks of
      storage under vacuum at 2 degrees C. Under aerobic conditions at 7 degrees C, all
      four of the strains grew well on the beef samples. C. maltaromicus LV17 and UAL26
      and Lb. sake Lb706 all caused off-odours and discoloration. The rate of aerobic
      deterioration in meat quality was faster with increased time of storage under
      vacuum. L. gelidum UAL187-22 could be a suitable antagonistic strain with the
      potential to extend the storage life of beef, stored anaerobically and packaged
      aerobically for retail sale, without producing undesirable sensory changes.

PMID- 7577362
TI  - Contribution of selected fungi to the reduction of cyanogen levels during solid
      substrate fermentation of cassava.
AB  - The effect of six individual strains of the dominant microflora in solid
      substrate fermenting cassava on cyanogen levels was examined. Six out of eight
      batches of disinfected cassava root pieces were incubated for 72 h after
      inoculation with either of the fungi Geotrichum candidum, Mucor racemosus,
      Neurospora sitophila, Rhizopus oryzae and Rhizopus stolonifer, or a Bacillus sp.,
      isolated from on-farm fermented cassava flours from Uganda. One non-inoculated
      batch was incubated as a reference. Levels of initial and final moisture and
      cyanogens were assayed. The experiment was done in quadruplicate. Incubation of
      disinfected root pieces reduced cyanogenic glucoside levels significantly to
      62.7% (SD 2.8) of the initial value. Microbial growth resulted in significant
      additional reduction of the cyanogenic glucoside levels to 29.8% (SD 18.9) of the
      levels which were obtained after non-inoculated incubation. Among the tested
      strains, N. sitophila reduced cyanogenic glucoside levels most effectively,
      followed by R. stolonifer and R. oryzae. Of all fermented samples, both Rhizopus
      spp. showed highest proportion of residual cyanogens in the cyanohydrin form.
      Flours showed similar patterns of cyanogens as the batches they were prepared
      from. Cyanogenic glucoside level reduction was significantly correlated (r =
      0.86) with the extent of root softening. It is concluded that both incubation and
      microbial activity are instrumental in reducing the potential toxicity of cassava
      during the solid substrate fermentation and that effectiveness varies
      considerably between the species of microorganisms applied.

PMID- 7577363
TI  - Production of staphylococcal enterotoxin A in cream-filled cake.
AB  - Cakes were baked with normal ingredients and filled with cream, inoculated with
      different size enterotoxigenic-staphylococcal inocula. Samples of the cakes were
      incubated at room temperature and put in the refrigerator. Samples of cake and
      filling were taken at different times and analyzed for staphylococcal count and
      presence of enterotoxin. The smaller the inoculum, the longer the time required
      for sufficient growth (10(6)) to occur for production of detectable enterotoxin.
      Enterotoxin added to the cake dough before baking (210 degrees C, 45 min) did not
      survive the baking. The presence of enterotoxin in the contaminated cream filling
      indicated this as the cause of staphylococcal food poisoning from cream-filled
      cakes. Refrigeration of the cakes prevented the growth of the staphylococci.

PMID- 7577364
TI  - Transmembrane topology of the glutamate receptors. A tale of novel twists and
      turns.
AB  - The glutamate receptor subunits were first thought to cross the cell membrane
      four times in a manner analogous to the neuronal nicotinic acetylcholine, GABAA,
      and glycine receptors. This model led the field for nearly five years, although
      it was frequently in conflict with the data. Recently, comparisons with bacterial
      proteins, epitope tagging experiments, and the construction of chimeras has
      produced a new model of glutamate receptor topology that is novel and quite
      unlike any of the other receptors.

PMID- 7577365
TI  - Inducible nitric oxide synthase in the central nervous system.
AB  - There is an accumulation of evidence indicating that induction of the calcium
      independent isoform of nitric oxide synthase (iNOS) in glial cells can contribute
      to nitric oxide-mediated neural-cell damage. Elucidation of iNOS inducing signals
      and mechanisms regulating its augmentation and suppression may have implications
      for our understanding of basic processes underlying some forms of central nervous
      system disease.

PMID- 7577366
TI  - Inhibition of human neuroblastoma growth by a specific VIP antagonist.
AB  - The 28-amino-acid neuropeptide, vasoactive intestinal peptide (VIP), is a potent
      mitogen during embryonic development and plays a vital role in brain growth. VIP
      is also mitogenic for tumor cells, including the human neuroblastoma (NMB).
      Northern blot analysis has revealed VIP mRNA transcripts in NMB. We now report
      VIP-like immunoreactivity within these neuroblastoma cells that increased during
      logarithmic growth and decreased after attaining confluency. About 10(6) seeded
      cells secreted 5-40 pg of VIP-like immunoreactivity into the medium. These
      results suggest an autocrine role for VIP in the regulation of neuroblastoma
      growth. A VIP hybrid antagonist (neurotensin6-11 VIP7-28) that has been shown to
      inhibit lung cancer proliferation was now tested for inhibition of neuroblastoma
      growth. Receptor binding studies indicated that the hybrid antagonist displaced
      [125I]-VIP binding in the neuroblastoma cells (EC50 = 5 x 10(-6)M). Furthermore,
      as measured by thymidine incorporation and by cell counts, the potent VIP hybrid
      antagonist inhibited neuroblastoma multiplication in a dose-dependent manner. In
      conclusion, VIP may be an important regulator of growth of nerve cell progenitors
      and of tumors derived from neuronal origin and intervening with VIP function may
      lead to improved treatment of cancer.

PMID- 7577370
TI  - Sociobiology and cervical cancer.

PMID- 7577368
TI  - Characterization and regulation of the protein binding to a cis-acting element,
      RET 1, in the rat opsin promoter.
AB  - RET 1 is a binding site for retinal nuclear proteins located at -136 to -110 bp
      in the rat opsin promoter, as defined by DNase protection assays. A similar
      sequence is found in the upstream flanking regions of many other photoreceptor
      genes in mammals and other species, including Drosophila. A 7-base consensus
      sequence, CAATTAG, is found in these genes and has the binding activity of the
      longer RET 1 element. A 40-kDa protein that binds to RET 1 has been purified over
      2 x 10(5)-fold to apparent homogeneity by affinity chromatography. The RET 1
      binding activity is first detectable at E18 and increases during the first two
      postnatal weels, At embryonic ages the retarded bands show an altered mobility
      and at early postnatal ages two bands are detected, with the adult band
      increasing and the embryonic band decreasing in intensity. Treatment of early
      postnatal retinas with bFGF increased the binding activity in nuclear extracts
      and caused a shift in migration of the retarded band to a position characteristic
      of the embryonic form of the complex. The results support the hypothesis that RET
      1-like elements play an important role in rod photoreceptor development.

PMID- 7577367
TI  - NF-kappa B site-mediated negative regulation of the HIV-1 promoter by
      CCAAT/enhancer binding proteins in brain-derived cells.
AB  - Several transcription regulatory elements that interact with cellular DNA-binding
      proteins have been identified in the HIV-1 long terminal repeat (LTR). We have
      identified two sequence motifs in the U3 region of the LTR that are similar to
      the consensus 9-bp DNA-binding element of the CCAAT/enhancer-binding protein
      (C/EBP) family of transcription factors. One of the sequences (promoter-proximal)
      mapped immediately upstream of the NF-kappa B element, whereas the other
      (promoter-distal) completely overlapped the upstream stimulatory factor (USF)
      binding site. In this study, we investigated the role of the enhancer-proximal
      consensus C/EBP binding sequence in the expression of the HIV-1 LTR. In
      cotransfection assays we found that although this sequence is a functional C/EBP
      responsive element, the regulation of the HIV promoter by C/EBP is very complex.
      C/EBP isoforms inhibited the phorbol 12-myristate 13-acetate (PMA)-stimulated HIV
      1 promoter activity in human glioblastoma U138MG and neuroblastoma SHSY5Y cells,
      but not in HeLa epithelial cells, and this inhibition required the NF-kappa B
      element. C/EBP also downregulated the HIV NF-kappa B element-containing SV40
      early promoter activity, regardless of the presence of the flanking C/EBP-binding
      sequences, in the two brain-derived cells. In electrophoretic mobility shift
      assays with nuclear extracts from HeLa and U138MG cells, purified C/EBP markedly
      increased the complex formation between endogenous proteins and the NF-kappa B
      DNA probe without detectable association with the complex. However, with extracts
      from U138MG cells but not from HeLa cells, a slow migrating complex was observed.
      Our data suggest that the C/EBP family of transcription factors can downregulate
      the HIV-1 promoter activity in CNS-derived cells through the NF-kappa B binding
      elements.

PMID- 7577371
TI  - Current status of radiation sensitization by fluoropyrimidines.
AB  - Numerous clinical studies suggest that the combination of the fluoropyridimine
      fluorouracil and radiation is a more effective treatment for many cancers,
      especially gastrointestinal tumors, than is either modality alone. Also, the
      combination of fluorouracil and radiation has greatly expanded the possibilities
      for organ-preserving treatments, for example, in patients with bladder cancer.
      Another fluoropyridimine, floxuridine, administered via the hepatic artery, has
      been used in combination with irradiation in the treatment of patients with
      intrahepatic cancers and may prolong survival in patients with unresectable
      hepatobiliary malignancies. The beneficial effects of combining fluoropyrimidines
      and radiation are thought to be due to radiosensitization. More studies are
      needed to clarify the mechanism(s) of radiosensitization so as to optimize
      regimens in which the fluoropyrimidines are used.

PMID- 7577373
TI  - Clinical trials referral resource. Clinical trials with 9-aminocamptothecin.

PMID- 7577369
TI  - Both upstream and intragenic sequences of the human neurofilament light gene
      direct expression of lacZ in neurons of transgenic mouse embryos.
AB  - Initial expression of the neurofilament light gene coincides with the appearance
      of postmitotic neurons. To investigate the molecular mechanisms involved in
      neuron-specific gene expression during embryogenesis, we generated transgenic
      mice carrying various regions of the human neurofilament light gene (hNF-L) fused
      to the lacZ reporter gene. We found that 2.3 or 0.3 kb of the hNF-L promoter
      region directs expression of lacZ in neurons of transgenic embryos. Addition of
      1.8 kb hNF-L intragenic sequences (IS) enlarges the neuronal pattern of transgene
      expression. The 2.3-kb hNF-L promote lacZ-IS construct contains all regulatory
      elements essential for both spatial and temporal expression of the hNF-L gene
      during embryogenesis and in the adult. The use of a heterologous promoter
      demonstrated that the 1.8-kb hNF-L intragenic sequences are sufficient to direct
      the expression of lacZ in a NF-L-specific manner both temporally and spatially
      during development and in the adult. We conclude that these hNF-L intragenic
      sequences contain cis-acting DNA regulatory elements that specify neuronal
      expression. Taken together, these results show that the neurofilament light gene
      contains separate upstream and intragenic elements, each of which directs lacZ
      expression in embryonic neurons.

PMID- 7577372
TI  - New lymphatic mapping may avoid many axillary dissections.

PMID- 7577374
TI  - High-dose-rate intraoperative radiation therapy for colorectal cancer.
AB  - Last month, the authors presented the principles of high-dose-rate intraoperative
      radiation therapy (HDR-IORT), a new approach to intraoperative radiation
      delivery, as well as their criteria for patient selection, the goals of surgery,
      and their approach to minimizing surgical morbidity. This month, the authors
      present the technical aspects of delivering HDR intraoperative brachytherapy,
      their dosimetry atlas, and their results using HDR-IORT in the treatment of
      patients with colorectal cancer.

PMID- 7577375
TI  - Diagnosis and management of brachial plexus lesions in cancer patients.
AB  - Brachial plexus dysfunction is a well-known complication of cancer. Metastatic
      brachial plexus (RBP) are the most common causes. The distinction between MBP and
      RBP is very important but is not easy to make. This article presents in detail
      the distinguishing features of these types of brachial dysfunction. In regard to
      treatment, radiation, chemotherapy, narcotic analgesics, paravertebral nerve
      blocks, dorsal rhizotomy, dorsal root entry zone procedure, and high
      contralateral cordotomy are helpful in managing the symptoms of MBP. Transdermal
      electrical nerve stimulation, dorsal column stimulators, neurolysis, and
      neurolysis with omentoplasty have been tried in RBP. Good physical therapy,
      tricyclics, antiarrhythmics, anti-convulsants, nonsteroidal anti-inflammatory
      drugs and steroids are helpful in both conditions.

PMID- 7577376
TI  - Current status of vinorelbine for breast cancer.
AB  - Vinorelbine tartrate (Navelbine) is a new semisynthetic vinca alkaloid with
      efficacy against a variety of solid tumors, including non-small-cell lung cancer,
      breast cancer, head and neck cancer, and Hodgkin's lymphoma. Recently approved by
      the FDA for the first-line treatment of advanced non-small-cell lung cancer,
      vinorelbine is also under review by the FDA for use in patients with metastatic
      breast cancer. There is now extensive data confirming the activity of vinorelbine
      in metastatic breast cancer, with second-line response rates of 17% to 36% and
      first-line response rates of 40% to 44%. Investigators have combined vinorelbine
      with other active drugs against breast cancer to produce response rates exceeding
      50% for first-line therapy. Numerous centers are now conducting randomized trials
      comparing vinorelbine to established second-line therapies for advanced breast
      cancer, such as paclitaxel (Taxol). Future research is needed to further define
      the precise role of vinorelbine as a component of combination therapy for
      metastatic breast cancer.

PMID- 7577377
TI  - Many factors prevent women with breast cancer symptoms from seeking medical help
      quickly.

PMID- 7577378
TI  - Navelbine promising as a radiosensitizer in non-small-cell lung cancer.

PMID- 7577379
TI  - Phase II study shows that significantly fewer rhIL-11 treated patients require
      platelet transfusions.

PMID- 7577381
TI  - Tumor necrosis factor-alpha in children with human immunodeficiency virus
      infection.

PMID- 7577380
TI  - Computers in medicine.

PMID- 7577382
TI  - Family-based oncology care: a necessary clinical and research partnership.

PMID- 7577383
TI  - Pediatric oncohematology in Bulgaria.

PMID- 7577384
TI  - History and present organization of pediatric oncology in Germany.

PMID- 7577386
TI  - Influence of treatment modalities on prepubertal growth in children with acute
      lymphoblastic leukemia.
AB  - The statural growth of 85 prepubertal children treated for acute lymphoblastic
      leukemia was evaluated in a longitudinal study over 4.5 years. Patients were
      divided into three groups according to central nervous system prophylaxis: 37
      patients received cranial irradiation with a dose of 24 Gy, 15 received a dose of
      18 Gy, and 33 were not irradiated. According to the risk of leukemia, patients
      were divided into normal-risk (n = 74) and high-risk (n = 11) groups. The
      duration of treatment was 2 years, during which all patients showed growth
      retardation. The relative standard deviation score for height declined from 0 to 
      0.7 for the irradiated patients and from 0 to -0.2 for the non-irradiated group
      (P = 0.0001). There was no difference in growth pattern between cranial
      irradiation with 18 versus 24 Gy and chemotherapeutic treatment according to high
      risk versus normal-risk protocols. However, a negative synergistic effect of more
      intensive chemotherapy and cranial irradiation on growth was demonstrated.

PMID- 7577385
TI  - Hybrid (COPP/ABV) therapy in childhood Hodgkin's disease: a study of 53 cases
      during 1989-1993 at the Cancer Institute, Madras.
AB  - The optimal therapy for children with Hodgkin's disease is controversial. Between
      1989 and 1993, 53 children under 14 years of age with Hodgkin's disease were
      treated with COPP/ABV (cyclophosphamide, vincristine, procarbazine,
      prednisolone/adriamycin, bleomycin, vinblastine) hybrid chemotherapy. The results
      were analyzed with the Kaplan-Meier product limit method for survival and the
      Logrank test for predicting statistical significance. Ten patients (18.87%) had
      early-stage disease (I to IIA) and 43 (81.13%) had advanced disease. Lymphocyte
      predominant histology was seen in 20 (37.5%) patients, nodular sclerosis in 8
      (15%), mixed cellularity in 21 (39.6%), and lymphocyte depletion in 4 (7.56%).
      The male:female ratio was 3.82:1. Complete responses were seen in 51 (96.22%)
      patients, with 47 (92.15%) of them in sustained first remission. The event-free
      survival rate is 90.3% to date. COPP/ABV hybrid chemotherapy is an effective
      primary therapy for all stages of Hodgkin's disease in children.

PMID- 7577387
TI  - Abdominal sonographic findings at primary diagnosis of acute lymphoblastic
      leukemia in children: a comparison with different clinical risk factors.
AB  - We evaluated the presence of abdominal organomegaly and lymphadenopathy with
      ultrasound in 92 children with acute lymphoblastic leukemia (ALL) prior to
      chemotherapy, and compared these findings with the different immunophenotypes,
      age groups, and white blood cell (WBC) counts as well as the survival of the
      patients and the clinical findings of organomegaly. All the patients (n = 13)
      with a WBC higher than 50/microL showed intra-abdominal pathology compared with
      the patients with a low WBC, of whom 37% (n = 18) had normal scans. The children
      with a high WBC count also had hepatomegaly (P = 0.003) and splenomegaly (P =
      0.06) significantly more often, and showed high echogenicity of the kidneys (P =
      0.001). Lymphadenopathy was found significantly more often in children with T
      cell leukemia (P = 0.005). The younger age groups (0 to 2 and 2 to 5 years of
      age) had hepatomegaly significantly more often (P = 0.02), and the youngest age
      group (0 to 2 years) showed increased echogenicity of the kidneys more often (P =
      0.04). Ultrasound showed hepatomegaly in 14 patients and splenomegaly in 23
      patients who were assessed clinically as normal. According to our results,
      abdominal ultrasound is a useful tool for evaluating abdominal organomegaly and
      the extramedullary leukemic burden and can give information that is not available
      in clinical examination. There was no statistical association between the primary
      ultrasonographic findings and the patients' later survival.

PMID- 7577389
TI  - Social activities in the families of children with acute lymphoblastic leukemia.
AB  - The social activities of 15 children with acute lymphoblastic leukemia (ALL) and
      their families (index families) were compared during chemotherapy with those of
      control families matched for the numbers, ages, and sex of the children. Data
      concerning the day care arrangements for the children of all the index and
      control families were obtained by a questionnaire. The children under school age
      in the index families were more frequently cared for at home or in a family than
      were those in the control families (14/14 vs 13/26, P < 0.01). All visits made,
      visitors received, and gatherings of 12 index and 12 control families were
      recorded by means of diaries during two 4-week periods in May and September 1989.
      The adults and children in the ALL families made an average of 5.5 and 3.4 visits
      per person, respectively, during each 4-week period, with the corresponding
      figures for the control families being 5.4 and 4.4. The mean number of adult and
      child guests in the index and the control families and the corresponding figures
      for visits were similar. The mean numbers of adults and children present at
      places visited by an index and control family did not differ statistically
      significantly, and the mean number of gatherings attended per adult and child
      during a period of 4 weeks was also similar in both groups of families. The
      differences were found in day care arrangements, but social activities as
      recorded by visits and gatherings were similar in the families of the children
      with ALL and the controls.

PMID- 7577388
TI  - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in children
      undergoing high-dose chemotherapy and autologous peripheral blood stem cell
      transplantation.
AB  - The incidence of SIADH (the syndrome of inappropriate antidiuretic hormone
      secretion) was analyzed retrospectively in 43 children who received marrow
      ablative chemotherapy before autografts with peripheral blood stem cells for
      lymphoid malignancies. SIADH was documented in three children (ages 3, 13, and 13
      years) who received chemotherapy, which included high-dose methyl 6-[3
      (chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) and
      cyclophosphamide, under a concomitant overhydration protocol. SIADH was
      manifested as frequent vomiting in two patients and as generalized seizure in
      one. Hyponatremia (< 125 mEq/L), hypo-osmolality (< 260 mOsm/kgH2O), and
      continued urinary excretion of sodium (> 30 mEq/L) were used to diagnose SIADH in
      these three patients. All signs and symptoms subsided within 24 hours either by
      fluid restriction alone (n = 1) or by supportive care including anticonvulsant
      and D-mannitol, or hyperhydration with saline plus 5% glucose and diuretic. None
      of the patients died. Careful monitoring of the serum sodium level, as well as
      the osmolality of plasma and urine, should be incorporated into the patient
      management protocol for this type of high-dose chemotherapy.

PMID- 7577390
TI  - Intrathecal chemotherapy-related myeloencephalopathy in a young child with acute
      lymphoblastic leukemia.
AB  - Since the mid-1960s intrathecal chemotherapy (methotrexate [MTX], cytarabine [Ara
      C], or both, plus hydrocortisone) has constituted the standard approach to
      prophylaxis and treatment of central nervous system (CNS) leukemia and lymphoma.
      Intrathecal chemotherapy-related neurotoxicity has been described in a variable
      proportion of patients. At least 35 cases of subacute myeloencephalopathy with
      transient or permanent paraplegia/quadriplegia after intrathecal chemotherapy
      have been reported. Different factors have been cited: high cumulative MTX dose,
      meningeal leukemia, cranial irradiation, and preservatives in MTX and Ara-C. A
      direct toxic effect of the intrathecal chemotherapy seems the most likely
      mechanism. Early imaging studies are usually normal. We describe a nonfatal case
      of permanent flaccid quadriplegia after the fourth triple intrathecal
      chemotherapy in a 6-year-old girl with acute lymphoblastic leukemia and no
      evidence of meningeal involvement. Six months after intrathecal chemotherapy, CNS
      magnetic resonance imaging showed severe atrophy of spine, cerebellum, and
      cerebral hemispheres. The outcome of reported cases is diverse. No treatment has
      been shown to reverse neurotoxicity. Among the cases reported in the literature,
      complete recovery of neurologic deficits was observed in 9 patients, partial
      recovery with variable sequelae in 6, no recovery in 8, and 13 patients died from
      the initial oncologic disease or neurotoxicity progression.

PMID- 7577391
TI  - High-dose cytosine arabinoside and viridans streptococcus sepsis in children with
      leukemia.
AB  - We report three cases of fulminant sepsis due to viridans streptococci in
      leukemic children treated with high-dose cytosine arabinoside (Ara-C). The major
      predisposing factors to this occurrence are the presence of oropharingeal
      mucositis, which is the entry of streptococci into the bloodstream, and the use
      of antibiotic prophylactic regimens against gram-negative bacteria. In order to
      avoid fatal events during viridans streptococci sepsis, specific measures such as
      penicillin prophylaxis or early antibiotic treatment are needed. We suggest that
      the prompt empiric use of a glycopeptide antibiotic in addition to the
      conventional association of a beta-lactam plus an aminoglycoside may
      significantly decrease the mortality rate due to fulminant streptococci sepsis
      while the patient is severely neutropenic. In this regard, our current policy
      considers the addition of an anti-gram-positive antibiotic to the first-choice
      fever treatment in neutropenic patients who have received high-dose Ara-C.

PMID- 7577392
TI  - Comparative effect of 100 versus 250 micrograms/m2/day of G-CSF in pediatric
      patients with neutropenia induced by chemotherapy.
AB  - In pediatric patients with various malignancies, the effect of two different
      doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on
      chemotherapy-induced neutropenia was examined. Each patient was treated with two
      courses of the same chemotherapeutic regimen. Following each course, either 100
      micrograms/m2 or 250 micrograms/m2 of rhG-CSF was infused daily starting 48 hours
      after the cessation of chemotherapy and continuing for 14 consecutive days. A
      total of 29 patients (34 cycles of therapy) were eligible for the study. Both the
      duration of neutropenia (< 0.5 x 10(9)/l) and median days from the nadir of
      neutrophils to recovery, > 0.5 x 10(9)/l, were significantly shorter when 250
      micrograms/m2 was given. Moreover, the nadir counts of neutrophils and the
      duration of fever with neutropenia were, although not significant, in favor of
      250 micrograms/m2 administration. No differences were observed in the frequency
      and severity of side effects.

PMID- 7577393
TI  - Natural killer cell activity in a patient with Chediak-Higashi syndrome submitted
      to bone marrow transplantation.

PMID- 7577394
TI  - A case of mucoepidermoid carcinoma of the parotid gland developing in a child
      after the treatment of acute lymphoblastic leukemia.

PMID- 7577395
TI  - Treatment of chronic ITP.

PMID- 7577397
TI  - How would you treat a 4-year-old boy with nephrotic syndrome in relapse with
      ascites developed peritonitis and abdominal pain?

PMID- 7577396
TI  - Neonatal Fanconi syndrome due to deficiency of complex III of the respiratory
      chain.
AB  - Fanconi syndrome is an important presentation of respiratory chain disease. We
      report three patients who presented in the neonatal period with Fanconi syndrome,
      lactic acidosis and intrauterine growth retardation. In all three patients the
      major biochemical defect was in complex III of the mitochondrial respiratory
      chain, a relatively uncommon defect. The diagnosis could only be made by muscle
      biopsy as the defect was not expressed in cultured skin fibroblasts. Treatment
      with vitamins C and K3 and ubiquinone did not alter the course of the disease and
      all patients died before the age of 4 months.

PMID- 7577400
TI  - Who is likely to benefit from dialysis or from a kidney transplant?

PMID- 7577399
TI  - Urinary excretion of adenosine deaminase binding protein in neonates treated with
      tobramycin.
AB  - The potential tubulotoxicity of tobramycin and cefotaxim were assessed in
      neonates by measuring the urinary level of adenosine deaminase binding protein
      (ABP) and urinary alpha 1-microglobulin and beta 2-microglobulin. In a
      prospective study, 33 neonates who received tobramycin and cefotaxim for
      suspected neonatal sepsis were compared with 48 untreated newborns during the
      first 10 days of life. The urinary concentrations of ABP and its excretion rates,
      corrected for body weight and body surface area, were significantly increased
      from the 1st day of treatment. Urinary alpha 1-microglobulin and beta 2
      microglobulin were not elevated under tobramycin and cefotaxim during the first 2
      days of treatment. We conclude that ABP may be a sensitive marker for the
      detection of proximal renal tubular injury during tobramycin and cefotaxim
      treatments of neonates. The increase in urinary ABP which occurs before an
      elevation of urinary alpha 1-microglobulin and beta 2-microglobulin may reflect
      earlier structural than functional alterations. However, since none of the
      treated infants had signs of electrolyte disorders or glomerular dysfunction, the
      clinical relevance of ABP measurement should be reevaluated.

PMID- 7577401
TI  - Magnesium homeostasis in premature and full-term neonates.
AB  - Renal handling of magnesium (Mg) has not been comprehensively studied in the
      newborn period due to the difficulty, until recently, of measuring the diffusible
      fraction of plasma Mg (UfMg). In the present study this methodology was used to
      assess Mg homeostasis in 84 newborn infants of different postconceptional age (26
      42 weeks), weight (720-4,830 g) and postnatal age (1-72 days). Very premature
      infants (postconceptional age less than 35 weeks) had significantly higher values
      of plasma Mg than mature newborn infants. Plasma Mg related inversely to
      postconceptional age, weight, plasma total protein and plasma calcium, and
      directly to plasma potassium. Stepwise multiple regression analysis revealed that
      postconceptional age was the unique factor contributing to variations in plasma
      Mg. Plasma values of UfMg were the same in preterm as in term infants but, when
      expressed as a fraction of total plasma Mg (UfMg/Mg), they were significantly
      lower in very preterm infants. Fractional excretion of Mg and the ratio of urine
      Mg to urine creatinine did not vary as a function of postconceptional age. These
      results indicate that plasma UfMg is kept constant at different gestational ages
      despite variations in total plasma Mg; furthermore, no functional immaturity is
      present for renal tubular reabsorption of Mg, even in very low birth weight
      infants.

PMID- 7577402
TI  - Urinary albumin excretion in Spanish children. Nino Jesus Group.
AB  - We measured urinary albumin excretion in 2,224 school-children (1,168 boys, 1,056
      girls) aged 2-18 years, between 1989 and 1990 to establish reference values. We
      recorded all pathological antecedents and findings from physical examination,
      including anthropometric parameters and arterial blood pressure. The analytical
      study included serum total protein, albumin and creatinine. The second-morning
      urine and the nightly (rest) 10-h urine sample were collected and we determined
      the concentration of albumin and creatinine. We found a positive statistically
      significant correlation between the urinary albumin excretion (micrograms/10 h)
      and age, height, weight and body surface area. We suggest that it would be useful
      to relate the urinary albumin excretion to body surface area. The mean value for
      albumin excretion was 3.49 micrograms/ml in boys and 3.63 micrograms/ml in girls.
      The urinary albumin/creatinine ratio showed a high correlation with the albumin
      excretion (r = 0.958).

PMID- 7577398
TI  - Medullary nephrocalcinosis in nephropathic cystinosis.
AB  - Children with nephropathic cystinosis excrete large amounts of calcium and
      phosphate due to renal tubular Fanconi syndrome, and also receive substantial
      supplements of phosphate and alkalinizing agents. Since these constitute risk
      factors for nephrocalcinosis, we evaluated 41 children age 2 months to 15 years
      with nephropathic cystinosis and good renal function by performing
      retroperitoneal ultrasound examinations in a blinded fashion. We also
      retrospectively analyzed parameters of calcium and phosphate metabolism
      representing 216 person-years of data on these children. Fifteen children had no
      evidence of medullary nephrocalcinosis, while 18 had mild nephrocalcinosis, and 8
      severe nephrocalcinosis; 5 had renal stones. Mean urine calcium and phosphate
      concentrations increased from 1.47 mM and 5.30 mM, respectively, in children
      without nephrocalcinosis to 1.60 mM and 5.69 mM in children with mild
      nephrocalcinosis to 1.66 mM and 6.19 mM in children with severe nephrocalcinosis.
      Mean urine pH ranged from 7.5 to 8.1. The mean (+/- SD) age of the 26 patients
      with nephrocalcinosis was 9.4 +/- 3.8 years compared with 5.1 +/- 3.8 years for
      those without nephrocalcinosis (P < 0.005). Serum calcium, phosphate, vitamin D,
      and parathyroid hormone did not correlate with frequency or degree of
      nephrocalcinosis. We conclude that nephrocalcinosis frequently accompanies
      nephropathic cystinosis, can be detected by ultrasound examination, and might be
      managed by reducing oral replacement of phosphate, calcium, vitamin D, and
      citrate. Consideration should be given to truncating phosphate replacement once
      bone growth ceases.

PMID- 7577403
TI  - Spectrum of infections in Indian children with nephrotic syndrome.
AB  - We conducted a retrospective analysis of infections in 154 children (114 boys, 40
      girls) with nephrotic syndrome who satisfied the International Study of Kidney
      Disease in Children criteria. Their mean age at onset of symptoms was 6.2 years
      (range 6 months to 16 years) and the mean duration of follow-up was 32 months
      (range 6-55 months). One or more infectious complications were observed in 59 of
      the 154 children (38%), with urinary tract infection being the commonest (13.7%),
      followed by pulmonary tuberculosis (10.4%), peritonitis (9.1%), skin infections
      (5.2%), upper respiratory infections (5.2%), lower respiratory tract infections
      (3.9%) and pyomeningitis (0.6%). There were 3 deaths, the mortality in 2 patients
      being attributable to infections. There was no significant difference between
      children who developed infection and those who didn't in terms of age of onset,
      sex, duration of disease, serum creatinine, blood urea nitrogen and 24-h
      proteinuria. However, the children who developed infectious complications had
      significantly higher serum cholesterol levels (P < 0.01) and lower serum albumin
      levels (P < 0.02). The frequency of infections was higher in children who were
      frequent relapsers, steroid dependent and subsequent non-responders (28/60)
      compared with infrequent relapsers and initial non-responders (29/94).

PMID- 7577404
TI  - Validity of G1-cells in the differentiation between glomerular and non-glomerular
      haematuria in children.
AB  - Urine samples from 100 children and adolescents with micro- or macrohaematuria
      were investigated using phase contrast microscopy to establish the percentage of
      G1-cells that could differentiate glomerular from non-glomerular haematuria. The
      G1-cell is a special form of dysmorphic erythrocyte which seems to be specific
      for glomerular haematuria. Glomerular haematuria, defined by clinical criteria
      from biopsy, physical examination, standard laboratory evaluation and family
      history, was observed in 51 patients (group 1). Non-glomerular haematuria was
      found in 49 patients (group 2). The latter group had urinary tract infections,
      urolithiasis, hypercalciuria or haematuria caused by urological operation or
      diagnostic procedure. The percentage of dysmorphic erythrocytes differed
      significantly between the two groups studied (42 +/- 3% in group 1 vs. 6 +/- 1%
      in group 2, mean +/- SEM, P < 0.01); there was also a significant difference in
      G1-cells (19.4 +/- 1.7% in group 1 vs. 0.6 +/- 0.2% in group 2, mean +/- SEM, P <
      0.01). When glomerular haematuria was defined on the basis of > or = 30%
      dysmorphic erythrocytes by phase contrast microscopy, sensitivity, specificity
      and efficiency were 71%, 100% and 85%, respectively. When glomerular haematuria
      was defined on the basis of > or = 5% G1-cells, sensitivity, specificity and
      efficiency were 100%, 100% and 100%, respectively. The differentiation of
      glomerular and non-glomerular haematuria in children by determination of G1-cells
      appears to be more sensitive and efficient than the determination of the
      percentage of dysmorphic erythrocytes by phase contrast microscopy.

PMID- 7577406
TI  - Ureteral obstruction in the neonatal guinea pig: interaction of sympathetic
      nerves and angiotensin.
AB  - The contribution of sympathetic nerves to the hemodynamic effects of unilateral
      ureteral obstruction (UUO) was investigated in the neonatal guinea pig. The left
      ureter was partially constricted (or sham-operated) at birth, and sympathetic
      innervation was inhibited by guanethidine and compared with saline vehicle
      treated animals. At 15-20 days of age, blood pressure, cardiac output, total
      vascular resistance (TVR), renal blood flow, and renal vascular resistance (RVR)
      were determined before and after infusion of enalapril. UUO reduced cardiac
      output, increased TVR, and increased RVR of the ipsilateral kidney, whereas
      guanethidine treatment had no additional effects. Enalapril decreased RVR only in
      obstructed kidneys and not in intact opposite kidneys of animals with UUO. This
      was not affected by guanethidine administration. In contrast, enalapril decreased
      RVR only in guanethidine-treated (but not saline-treated) sham-operated guinea
      pigs. Therefore, UUO increases angiotensin-dependent vascular tone of the
      ipsilateral kidney independent of renal innervation. However, UUO decreases
      angiotensin-mediated vascular tone of the contralateral kidney, an effect
      unmasked by sympathectomy.

PMID- 7577405
TI  - A comparison of amitriptyline, vasopressin and amitriptyline with vasopressin in
      nocturnal enuresis.
AB  - Forty-five children aged 6-14 years with primary nocturnal enuresis were
      randomised to determine whether desmopressin is more effective than amitriptyline
      and whether the combination of amitriptyline/desmopressin is more effective than
      amitriptyline or desmopressin alone. Amitriptyline dosage was 25 mg for children
      6-10 years and 50 mg for children aged 10-14 years. Desmopressin (20 micrograms)
      was given in the same dosage for all age groups. After a run-in period of 2
      weeks, children were treated for 16 weeks and then observed for 12 weeks. In the
      amitriptyline group mean wet nights per week decreased from 5.8 +/- 0.9 to 3.3 +/
      1.9 (P < 0.0005); in the desmopressin group mean wet nights per week decreased
      from 6.0 +/- 0.9 to 4.7 +/- 1.7 (P < 0.02); in the amitriptyline/desmopressin
      group mean wet nights per week decreased from 6.3 +/- 0.9 to 3.3 +/- 2.5 (P <
      0.0006). When comparing the groups, amitriptyline/desmopressin and amitriptyline
      were statistically more effective than desmopressin in week 6 (P < 0.009), week 8
      (P < 0.03) and week 10 (P < 0.04). No significant side effects occurred. At this
      dose amitriptyline was more effective than desmopressin and the combination of
      desmopressin and amitriptyline did not confer any additional benefit.

PMID- 7577408
TI  - Recombinant human growth hormone in infants and young children with chronic renal
      insufficiency. Genentech Collaborative Study Group.
AB  - Children with chronic renal insufficiency (CRI) secondary to congenital
      structural abnormalities frequently have significant growth retardation by 2
      years of age. In a multicenter placebo-controlled study of the use of recombinant
      human growth hormone (rhGH), 30 of 125 (24%) participants were < 2.5 years of age
      at enrollment. Since the treatment arms of the study were balanced for age at
      randomization, data for these patients were examined for efficacy and safety.
      During the first 2 years of the study, approximately two-thirds of the patients
      (n = 19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n = 11)
      received placebo injections. At entry into the study, the mean (+/- SD)
      calculated creatinine clearance was 29.2 +/- 14.3 (range 12.0-63.7) ml/min per
      1.73 m2 in the rhGH-treated group and 23.3 +/- 15.1 (range 8.0-59.4) ml/min per
      1.73 m2 in the placebo-treated group. The 1st year growth rate was 14.1 +/- 2.6
      cm/year for the rhGH-treated group and 9.3 +/- 1.5 cm/year in the placebo-treated
      group (P < 0.00005). During the 2nd year of the study, the growth rate was 8.6 +/
      1.2 cm/year in the rhGH-treated group compared with 6.9 +/- 1.0 in the placebo
      group (P = 0.025). The delta height standard deviation score was +2.0 +/- 0.7 for
      the rhGH-treated group compared with -0.2 +/- 1.1 in the placebo-treated group (P
      < 0.00005) during the 2 years of the study. Minor adverse events occurred with
      similar frequency in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577407
TI  - Ureteral obstruction in the neonatal rat: renal nerves modulate hemodynamic
      effects.
AB  - In the neonate, chronic unilateral ureteral obstruction (UUO) reduces renal blood
      flow (RBF) of the ipsilateral kidney and increases RBF of the opposite kidney. To
      determine whether renal nerves mediate or modulate these responses, complete left
      UUO in the neonatal rat was used as a model of severe obstructive uropathy, and
      was compared with sham-operated controls. At 24-28 days of age, animals underwent
      left or right mechanical renal denervation or left sham renal denervation. One
      week after denervation, animals were anesthetized and blood pressure and heart
      rate were measured. Cardiac output and RBF were determined by the radioactive
      microsphere technique. UUO increased blood pressure and heart rate, and decreased
      RBF in the obstructed kidney, regardless of denervation. While left UUO increased
      RBF to the intact opposite kidney in rats with left renal denervation, this was
      attenuated by right renal denervation. Thus, in the neonatal rat, UUO modulates
      systemic renal hemodynamics, possibly through activation of the renin-angiotensin
      system. While renal nerves do not mediate the vasoconstriction of the obstructed
      kidney, renal nerves modulate vascular tone of the kidney contralateral to UUO.

PMID- 7577411
TI  - Azathioprine-induced pulmonary haemorrhage in a child after renal
      transplantation.
AB  - We report a case of azathioprine-induced haemorrhagic alveolitis, in a 14-year
      old boy, after renal transplantation. On day 25 the patient developed
      haemoptysis, fever and hypoxaemia. Chest X-ray showed diffuse reticulo-nodular
      shadows in both lung fields. Bronchoalveolar lavage samples were haemorrhagic and
      demonstrated a relative neutrophilia and a mild lymphocytosis, with a normal
      CD4/CD8 ratio. Azathioprine was discontinued on day 26. The patient required
      mechanical ventilation for 4 days. A positive leucocyte migration inhibition test
      and the recurrence of the symptoms after a second short course of azathioprine
      therapy suggested a cell-mediated mechanism. This patient is, to our knowledge,
      the first child to suffer from azathioprine-induced pulmonary haemorrhage.

PMID- 7577409
TI  - Differential effects of recombinant human growth hormone on glomerular filtration
      rate and renal plasma flow in chronic renal failure.
AB  - In normal subjects recombinant human growth hormone (rhGH) increases glomerular
      filtration rate (GFR) and effective renal plasma flow (ERPF) through the action
      of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and
      para-aminohippuric acid in 18 children with chronic renal failure (CRF) during
      their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term
      (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age
      was 9.1 (4.9-13.9) years, GFR 19 (9-58) and ERPF 77 (34-271) ml/min per 1.73 m2.
      During treatment height velocity increased from 4.5 (1.7-6.5) to 9.5 (4.8-12.7)
      cm/year (P < 0.0001). Two children required dialysis after 0.75 years and 1 child
      was electively transplanted after 0.5 years. There were no other serious adverse
      events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained
      constant on day 8, 22 (6-56) and after 1 year, 20 (9-59) ml/min per 1.73 m2. ERPF
      increased to 96 (33-276) ml/min per 1.73 m2 on day 8 (P = 0.005), and remained
      elevated, but not significantly so, at 99 (24-428) ml/min per 1.73 m2 at 1 year.
      Fasting IGF-I increased from 147 (46-315) ng/ml to 291 (61-673) by day 8 (P <
      0.003), and to 341 (101-786) ng/ml at 1 year. There was no correlation between
      the change in IGF-I and renal function. Blood pressure, albumin excretion and
      dietary protein intake were unchanged by treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577412
TI  - Aetiology of nephrolithiasis in north Indian children.
AB  - The aetiology of nephrolithiasis was investigated in 32 north Indian children (25
      boys, 7 girls, mean age 7.9 +/- 3.3 years). An underlying disorder was detected
      in 16 (50%) patients and included idiopathic hypercalciuria (8 patients),
      hyperoxaluria (3 patients) and renal tubular acidosis, primary
      hyperparathyroidism and hyperuricosuria (1 patient each). Magnesium ammonium
      phosphate calculi were found in 2 patients with recurrent urinary tract
      infections, 1 of whom had a duplex pelvic collecting system. In 16 patients (50%)
      a cause for renal calculi was not identified. Our findings suggest that an
      underlying disorder is present in a large proportion of children with
      nephrolithiasis where appropriate treatment may be beneficial.

PMID- 7577413
TI  - Acute renal failure due to xanthine stones.
AB  - A 9-month-old child with the skeletal abnormalities of Fuhrmann's syndrome
      presented with acute renal failure secondary to bilateral renal calculi.
      Hereditary xanthinuria was shown to be the underlying metabolic defect. Treatment
      with allopurinol was unsuccessful at reducing the xanthine excretion.

PMID- 7577414
TI  - Nephrotic syndrome related to systemic lupus erythematosus after griseofulvin
      therapy.
AB  - We report a 16-year-old male who developed nephrotic syndrome related to
      membranous glomerulopathy with clinical and serological evidence of systemic
      lupus erythematosus after treatment with griseofulvin. To our knowledge, this is
      the first case of griseofulvin-exacerbated lupus in which nephrotic syndrome has
      been observed.

PMID- 7577410
TI  - The cognitive development of pre-school children treated for chronic renal
      failure.
AB  - Chronic renal failure in young children is associated with impaired cognitive
      development, but recent studies present a more optimistic perspective. An
      important question is whether the earlier initiation of renal replacement therapy
      (RRT) might prevent the reported developmental retardation. The cognitive
      development of 31 patients (age < 5 years with a serum creatinine clearance of <
      20% of normal) undergoing different treatment modalities was monitored by
      repeated measurements during a prospective 3-year study. Fifteen patients
      received conservative treatment and 16 patients were on dialysis treatment at the
      start of the project. We were able to evaluate the effect of the onset of RRT on
      12 patients who were transferred from conservative treatment to dialysis. At the
      beginning of the study, the cognitive development of the total group was
      significantly delayed (mean developmental index = 78.5, SD = 19.5) compared with
      a normal population. Patients undergoing conservative treatment scored
      significantly higher (P < 0.01) than those on dialysis. The effect of starting
      dialysis treatment appeared to be positive, but only a significant short-term
      improvement was observed. Follow-up evaluation of 7 patients on conservative
      treatment and of 9 dialysis patients over a 2-year period did not show any
      significant change in a positive or negative direction. The present study
      revealed that pre-school dialysis patients are at risk with respect to their
      cognitive development. This is particularly true for the group with concomitant
      disorders. Less severe disease in the group on conservative treatment may be
      assumed to be a positive contributing factor to the more normal performance of
      these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577416
TI  - Early-onset chronic renal failure as a presentation of infantile nephropathic
      cystinosis.
AB  - We report an 18-month-old girl who presented in chronic renal failure after an
      illness characterised by protracted diarrhoea, poor weight gain and anaemia.
      There were no symptoms and signs suggestive of a renal Fanconi syndrome, but a
      diagnosis of nephropathic cystinosis was suggested by renal biopsy and confirmed
      by an elevated leucocyte cystine concentration. We suggest that the diagnosis of
      cystinosis should be considered in any child with chronic renal failure of
      unknown aetiology.

PMID- 7577417
TI  - Tuberculous osteomyelitis: an unusual case of tuberculous infection in a child
      undergoing continuous ambulatory peritoneal dialysis.
AB  - A 10-year-old boy on continuous ambulatory peritoneal dialysis had low-grade
      fever, pain and tenderness of the right shoulder; he had no history of infection
      or exposure to tuberculosis. The underlying granulomatous infection was diagnosed
      by histological examination of bone and the polymerase chain reaction with primer
      sequences specific for Mycobacterium tuberculosis. Special stains and cultures
      were negative. The initiation of antituberculous therapy was followed by a sharp
      improvement in the fever, malaise and shoulder pain within several weeks.
      Extrapulmonary tuberculosis is common in patients with chronic renal failure on
      dialysis and the diagnosis is difficult. The clinician must recognise the high
      and early mortality rate in order to initiate an aggressive diagnostic approach
      and early therapy.

PMID- 7577415
TI  - Acute renal failure associated with Candida albicans infection.
AB  - A 16-year-old male with a long history of steroid-responsive nephrotic syndrome
      developed fever, abdominal pain, thrombocytopenia and acute renal failure. The
      clinical course and renal histology were similar to, but not typical of,
      haemolytic uremic syndrome. Positive cultures (throat, oesophagus, stool), an
      elevation in serum levels of specific antibody and fungal polysaccharide (1,3)
      beta-D-glucan and response to the antifungal therapy indicated an association
      between this syndrome and infection with Candida albicans.

PMID- 7577418
TI  - Clinical use of tacrolimus (FK-506) in infants and children with renal
      transplants.
AB  - Although cyclosporine (CsA)-based immunosuppressive regimens have been highly
      successful in renal transplantation in infants and children, their adverse
      influence on somatic growth, general appearance, and blood pressure are of
      particular importance in this population. Over the past 4 years, we have utilized
      tacrolimus (formerly FK-506) as the primary immunosuppressive agent in 43
      unselected children and achieved 1-year and 3-year allograft survival rates of
      96% and 85%, respectively. We have also used tacrolimus to rescue 14 of 19 (74%)
      renal allografts from CsA-resistant rejection. Corticosteroids were discontinued
      in 62% of non-rescue patients without increasing the risk of rejection or renal
      dysfunction over a mean follow-up time of 25 months. Tacrolimus monotherapy has
      been associated with improved body growth and less obesity, while tacrolimus
      alone or in combination with prednisone was virtually free of hirsutism or
      gingival hypertrophy, and posed a low risk for hypertension. A major disadvantage
      of this regimen may be an increased risk for viral infections and a benign form
      of posttransplant lymphoproliferative disease. This article describes the
      tacrolimus protocol utilized in our center and focuses on practical clinical
      issues including therapeutic monitoring, benefits, and major toxicity in children
      with renal allografts.

PMID- 7577419
TI  - Role of platelets in progressive glomerular diseases.
AB  - There is increasing evidence that platelets are involved in the pathogenesis of
      glomerulonephritis. Intraglomerular platelets or their degradation products are
      observed in biopsies from patients with lupus nephritis, mesangioproliferative,
      membranous or IgA nephropathy. Moreover shortened platelet survival in patients
      with various glomerular diseases has also been described. In models of
      experimental glomerulonephritis, platelets may participate in glomerular injury,
      together with other mediators, by complex mechanisms. As extensively documented,
      platelets release within the glomerulus vasoactive, chemotactic and mitogenic
      substance that interact with a number of soluble mediators generated by renal
      resident or inflammatory cells and contribute to amplify glomerular injury. Thus
      platelet-activating factor and other platelet secretory products, polycationic
      macromolecules, platelet factor 4 and beta-thromboglobulin, alter glomerular
      permeability to proteins and enhance immune-mediated glomerular injury. Platelet
      derived factors, like platelet-derived growth factor (PDGF) and transforming
      growth factor beta (TGF beta) mediate renal disease progression in experimental
      and human glomerulonephritis via their chemotactic activity for infiltrating
      leucocytes and their effect of promoting extracellular matrix synthesis by
      resident renal cells. In these settings increased renal expression of PDGF and
      TGF beta has correlated with clinical features. Specific PDGF and TGF beta
      inhibitors ameliorated experimental glomerular disease. A wide variety of
      therapies to inhibit platelet function have been employed over the years, however
      the results of clinical studies are controversial and do not allow conclusions to
      be drawn about the efficacy of anti-platelet agents in progressive renal disease.
      Identification of specific platelet inhibitors or interventions specific for
      platelet secretory products and their target cells will be crucial for
      understanding the exact role of platelets and their products in glomerular
      disease.

PMID- 7577420
TI  - Neonatal hydronephrosis--the controversy and the management.
AB  - Neonatal hydronephrosis is being detected with increasing frequency. The majority
      of these cases have a tendency to resolve during infancy. Hydronephrosis is an
      anatomical entity that is not synonymous with obstruction. Review of the
      pathoembryology, the pathophysiology, the diagnostic techniques currently used
      and the natural history of hydronephrosis is given. The management and the
      controversies involved are discussed.

PMID- 7577421
TI  - The role of H(+)-ATPases in urinary acidification.

PMID- 7577423
TI  - Clinical quiz. Haemorrhagic fever with renal syndrome (HFRS) Korean haemorrhagic
      fever.

PMID- 7577425
TI  - Bone mineral content in children with nephrotic syndrome.

PMID- 7577424
TI  - Interferon treatment in hepatitis B virus-associated membranous glomerulopathy.

PMID- 7577426
TI  - Paediatric nephrology in poor countries: an educational and cultural outlook.

PMID- 7577427
TI  - Malaria. Local transmission of Plasmodium vivax malaria, Houston, Texas, 1994.

PMID- 7577428
TI  - Expanded programme on immunization (EPI). Lot Quality Assurance survey to assess
      immunization coverage.

PMID- 7577422
TI  - Transmembrane signaling in kidney health and disease.
AB  - Transmembrane signal transduction is the process whereby a ligand binds to the
      external surface of the cell membrane and elicits a physiological response
      specific for that ligand and cell type. It is now appreciated that numerous
      disease states represent disturbances in normal transmembrane signaling
      mechanisms. In the current paper, we focus our attention on the mesangial cell of
      the glomerular microcirculation as a prototypical model system for understanding
      normal and abnormal transmembrane signaling processes. Among the major receptor
      and effector mechanisms for transmembrane signal transduction in the mesangial
      cell, this paper emphasizes the phospholipase effector response to growth factors
      and vasoactive hormones. The post-translational and transcriptional pathways for
      regulation of phospholipase C and phospholipase A2 are described, including
      consideration of perturbations in these systems that characterize two disease
      models, namely: acute cyclosporine nephrotoxicity and early diabetic
      glomerulopathy.

PMID- 7577429
TI  - Veterinary public health. Human rabies in the Americas.

PMID- 7577430
TI  - Leprosy disabilities: magnitude of the problem.

PMID- 7577432
TI  - Schistosomiasis eradication.

PMID- 7577431
TI  - Influenza.

PMID- 7577433
TI  - The embryonic development of Pleurodeles waltl (Michah). Reappraisal of the
      Gallien-Durocher stage series.

PMID- 7577434
TI  - The chronological development of the urodele amphibian Pleurodeles waltl
      (Michah).

PMID- 7577435
TI  - What can be learned from intermediate filament gene regulation in the mouse
      embryo.
AB  - In recent years, intermediate filaments (IFs) have attracted much interest,
      largely because their constitutive polypeptide units are specifically expressed
      in various cell types and thus represent excellent differentiation markers. Data
      obtained through biochemical studies and molecular cloning have allowed the
      classification of IFs into five types according to their protein structure. The
      expression of most IF types is characteristic of a given cell type: cytokeratins
      (IF types I and II) are produced in epithelia, neurofilaments and alpha
      internexin (type IV) in neurons and nestin (type IV) in neuroblast and myoblast.
      On the other hand the four type III IFs are highly related proteins which are
      expressed in different cell types. Thus the study of type III IF gene regulation
      provides an excellent approach towards the analysis of cell-specific
      transcription. This review focuses on type III IF gene regulation during mouse
      embryogenesis and describes the latest data obtained through the combination of
      both in vitro (in cell lines) and in vivo (in transgenic mice) approaches. It
      appears that, while intragenic sequences play a major role in the regulation of
      the expression of the genes encoding other types of IFs, a major contribution to
      the transcriptional regulation of type III IF genes is brought by 5' upstream
      sequences. However, recent evidence obtained through the use of transgenic mice
      indicate that upstream sequences must cooperate with intragenic elements to
      establish the complex and dynamic expression pattern characteristic of type III
      IF genes. The very high similarity between the coding sequences of type III IF
      genes raises the question of the significance of the occurrence of four members
      of this class. We propose a model for the amplification of this small gene family
      based on the increasing complexity of expression patterns in higher organisms.
      This could have led first to the requirement for a highly sophisticated control
      region in an ancestral type III IF gene, followed by two successive gene
      duplications, thus leading to the appearance of four different regulatory regions
      directing the cell-specific transcription of nearly identical genes in different
      cell types.

PMID- 7577436
TI  - Comparison of expression of the msx-1, msx-2, BMP-2 and BMP-4 genes in the mouse
      upper diastemal and molar tooth primordia.
AB  - The existence of transient putative tooth anlagen in the prospective mouse upper
      diastema region has been documented previously in morphological studies. By in
      situ hybridization we investigated the expression patterns of the msx-1, msx-2,
      BMP-2 and BMP-4 genes, supposed to regulate early tooth development, in day 10-14
      mouse embryonic upper diastema and molar regions, using 49 series of frontal
      sections. On the basis of comparison of the temporo-spatial expression patterns
      in both diastemal and molar tooth primordia we conclude that each of the four
      genes was expressed at least for some period simultaneously and at a comparable
      developmental stage in the transient and persisting dental primordia. BMP-2 and
      BMP-4 expression was downregulated in the diastemal dental primordia during their
      regression starting at day 13. The temporo-spatial pattern of BMPs expression may
      be associated with the disappearance of diastemal rudiments. Contrary to the
      molar anlage, we did not detect msx-2 gene expression in the diastemal dental
      rudiments after the stage of epithelial thickening. The deficiency of the msx-2
      gene products may play a role in the growth retardation of diastemal dental
      primordia resulting in their subsequent involution.

PMID- 7577437
TI  - Desmin transgene expression in mouse somites requires the presence of the neural
      tube.
AB  - Transgenic mice were used to study the effect of the neural tube on somite
      myogenesis. These mice express a transgene in which the 1 kb DNA 5' regulatory
      sequence of the desmin gene is linked to a reporter gene which codes for E. coli
      beta-galactosidase. In order to determine whether the developmental fate of
      cells, specifically the prospective myogenic population, in newly developed
      somites was pre-determined, newly formed somites were isolated from the caudal
      region of day 9.5 transgenic embryos and transplanted into 8.5 day non-transgenic
      host embryos. Even though the implanted somites were not oriented in the host
      embryos, all the specimens examined developed normally at the graft site forming
      a dermatome, myotome and sclerotome in the correct anatomical positions. The
      myotome even expressed the desmin transgene. In addition, we isolated the 3 most
      caudal somites, that is, the most recently developed somites, from day 9.5
      transgenic embryos and maintained them on gelatin-coated coverslips in culture
      for up to 4 days. While these somite explants did not develop myoblasts, it was
      possible to induce myogenesis by introducing pieces of neural tube into the
      explant cultures. These results suggest that the developmental fate of cells
      within the newly formed somite is not predetermined, but is dependent on the
      microenvironment surrounding the developing somite.

PMID- 7577438
TI  - Alpha-tubulin marker gene of neural territory of sea urchin embryos detected by
      whole-mount in situ hybridization.
AB  - We have used Northern blot and whole-mount in situ hybridizations to analyze the
      temporal and spatial expression pattern of the Pl alpha 2 alpha-tubulin gene in
      Paracentrotus lividus sea urchin embryos. The Pl alpha 2 transcript is first
      detectable at 14 h post-fertilization (blastula stage) and it is only expressed
      in the oral ectoderm. The amount of transcripts of this gene increases throughout
      development and accumulates up to the pluteus stage. In this stage the Pl alpha 2
      transcript is localized in the neural structures of the embryo. We conclude that
      the Pl alpha 2 gene is an early neurogenic territory marker. Furthermore we have
      observed the same localization of the Pl alpha 2 transcript in the Zn(++)- or
      phenytoin-treated embryos, confirming the animal localization of the Pl alpha 2
      transcript and its specific relation to neurogenic territory, whose
      differentiation starts from few founder cells present at blastula stage.

PMID- 7577439
TI  - 4-aminopyridine acts as a weak base and a Ca2+ mobilizing agent in triggering
      oocyte meiosis reinitiation and activation in the Japanese clam Ruditapes
      philippinarum.
AB  - Ovarian oocytes of the prosobranch mollusc Patella vulgata and the pelecypod
      Ruditapes philippinarum are arrested during prophase of the first maturation
      division. Release from this blockade, which is revealed by germinal vesicle
      breakdown, drives these oocytes to a second arrest in metaphase I, at which time
      the oocytes become fertilizable. The respective roles of Ca2+ and H+ ion
      movements during this early step in meiosis reinitiation has not been fully
      established yet. In this work we reveal the presence of acidic vesicles and
      report that bafilomycin A1 and N,N'-dicyclohexylcarbodiimide, two inhibitors of
      the vacuolar-type H(+)-ATPase, applied to Ruditapes oocytes, produce a
      significant inhibition of their response to the natural neurohormone serotonin.
      Since sodium deprivation did not affect this response, this suggests that a v
      type ATPase pump, possibly located in the membrane of these acidic vesicles, may
      play a subtle role in the cascade of events that releases oocytes from their
      prophase block. We then describe how 4-aminopyridine, a drug reputed to be a K+
      channel antagonist, triggers both meiosis reinitiation and activation of Patella
      and Ruditapes oocytes. This agent acts as a weak base, its effect depending on
      external pH. Moreover, using the fluorescent probes BCECF and Fluo-3/AM, we
      observe that this drug both alkalinizes the endoplasm and promotes an
      intracellular Ca2+ surge. This dual effect may explain why Ruditapes oocytes no
      longer stop in metaphase under these conditions and behave like other bivalve
      species which are directly fertilizable at the germinal vesicle stage.

PMID- 7577440
TI  - The secretory material of the subcommissural organ of the chick embryo.
      Characterization of a specific polypeptide by two-dimensional electrophoresis.
AB  - The subcommissural organ (SCO) is a cerebral gland that releases into the
      cerebrospinal fluid a carbohydrate-rich glycoprotein which condenses to form
      Reissner's fiber (RF). Western blots from two-dimensional gel electrophoresis
      were stained with lectins (Concanavalin-A, wheat germ agglutinin) and anti-bovine
      RF serum to identify the secretory products of the chick embryo SCO.
      Immunohistochemical investigations showed that the anti-bovine RF serum reacted
      exclusively with the secretion of the SCO. Comparative protein patterns of SCO,
      pineal organ and cerebral hemisphere extracts allowed us to characterize a
      specific polypeptide in the SCO electrophoretic profiles. The polypeptide was a
      highly acid compound (isoelectric point of 4.7) with a high molecular weight (390
      kDa). On Western blots only this component was immunoreactive with the RF
      antiserum and it exhibited an affinity for the two lectins. On the basis of these
      results, this polypeptide may be considered as a specific component of the
      secretory material synthesized by the SCO cells of the chick embryo.

PMID- 7577441
TI  - Analysis of polysulfate-binding domains in porcine proacrosin, a putative zona
      adhesion protein from mammalian spermatozoa.
AB  - Proacrosin is one of the major proteins found within the acrosomal vesicle of
      mammalian spermatozoa. Previous work has shown that it binds non-enzymatically
      and with high affinity to polysulfate groups on zona pellucida glycoproteins
      (ZPGPs) thereby leading to the hypothesis that at fertilization it functions as a
      secondary ligand molecule to retain acrosome-reacted spermatozoa on the surface
      of the egg. In the present work we have investigated the nature and extent of the
      polysulfate binding domain on boar sperm proacrosin using a combination of group
      specific modifying reagents, fragmentation analysis, peptide synthesis and
      expression of deletion recombinants in E. coli bacteria. Taken overall, our
      results show that arginine, lysine and histidine residues located between Gly 93
      and Ala 275, together with the participation of His 47 and Arg 50, are necessary
      for maximum polysulfate binding activity. The secondary and tertiary structure of
      this central peptide domain is also important to ensure correct alignment of
      basic residues with complementary sulfate groups on ZPGPs. Proacrosin, therefore,
      has many properties in common with other polysulfate binding proteins, such as
      antithrombin III and sea urchin sperm binding, in having a conformation-dependent
      domain containing basic amino acids that mediates specific protein-protein
      interactions. These observations strengthen the hypothesis that proacrosin is a
      multifunctional protein with a major role as a ligand molecule at fertilization.

PMID- 7577442
TI  - Expression of paternal and maternal mitochondrial HSP70 family, hsc74, in
      preimplantation mouse embryos.
AB  - We have investigated the regulation of gene expression of a novel mitochondrial
      HSP70 family, hsc74 in preimplantation mouse embryos. We used a monoclonal
      antibody, anti-CSA, which reacts with only one of strain variants of the hsc74.
      By immunostaining with anti-CSA antibody, the hsc74 protein was constitutively
      detected in C3H embryos from 1-cell to blastocyst stage, but no signals were
      detectable in C57BL/6 embryos. To know the timing of paternal genome expression,
      we examined the expression of hsc74 in (C57BL/6 x C3H)F1 embryos. No positive
      signals were detectable in embryos before 8-cell stage. In early 8-cell stage
      weakly positive signals appeared in the peripheral region of the blastomeres.
      From late 8-cell stage, the protein was intensively detectable and was
      persistently expressed in all types of cells. We have also applied a sensitive
      methodology to distinguish genetic variants of hsc74 from C3H and C57BL/6 by
      reverse transcription polymerase chain reaction followed by single strand
      conformation polymorphism analysis. In (C57BL/6 x C3H)F1 embryos, the paternal
      transcripts were first detected in 4-cell embryos, while the maternal transcripts
      were constantly detectable. These results indicate that the transcripts and
      proteins of hsc74 were derived only from the maternal gene from 1-cell to 4-cell
      stages, and that from 4-cell stage the paternal gene is also transcribed, and the
      significant increase of the paternally derived protein occurred around late 8
      cell stage.

PMID- 7577443
TI  - Differential expression of neural cell adhesion molecule (NCAM) during
      osteogenesis and secondary chondrogenesis in the embryonic chick.
AB  - Progenitor cells in the periosteum-perichondrium of the posterior hook of the
      quadratojugal (QJ, a membrane bone) in the embryonic chick are bipotential for
      osteogenesis and chondrogenesis. These cells switch from osteogenesis to
      chondrogenesis between 10 to 11 days in normal (mobile) embryos but not in
      paralyzed (immobile) embryos. Expression of neural cell adhesion molecule (NCAM)
      was studied using a monoclonal antibody in QJ hooks from normal and paralyzed
      chick embryos between 10 and 21 days of incubation. NCAM is expressed in
      osteoprogenitor cells and osteoblasts but not in chondroprogenitor cells,
      chondroblasts, or chondrocytes. The switch of progenitor cell differentiation
      from an osteogenic to a chondrogenic pathway between 10 and 11 days of incubation
      coincides with down-regulation of NCAM expression. Both initiation of secondary
      chondrogenesis and down-regulation of NCAM depend on biomechanical stimulation.
      In embryos paralyzed at 9 days, secondary cartilage fails to form and progenitor
      cells remain positive for NCAM. Furthermore, paralysis influences NCAM expression
      in progenitor cells before secondary chondrogenesis morphologically begins,
      indicating that NCAM may play a role in the initiation of secondary
      chondrogenesis. In 15-day normal embryos, NCAM-positive cells accumulate between
      the perichondrium and secondary cartilage in a position that prevents further
      cartilage formation in the hook. In 19-day embryos, these cells lose their NCAM
      expression and restart chondrogenesis in a second phase of differentiation,
      forming an articular cartilage. Loss of NCAM expression in this cell layer and re
      commencement of chondrogenesis do not occur in embryos paralyzed at 13 days, and
      therefore also require biomechanical stimulation. Hence, down-regulation of NCAM
      expression correlates with two phases of secondary chondrogenesis in embryonic
      life, both of which are dependent upon embryonic movement.

PMID- 7577445
TI  - The role of vertical and planar signals during the early steps of neural
      induction.
AB  - The classical Einsteck-test (Spemann and Mangold, Roux Arch. Dev. Biol. 100: 599
      638, 1924) and data from total exogastrulae (Holtfreter, 1933) suggest that
      vertical signals are transmitted between the chordamesoderm (organizer) and
      reacting ectoderm in the early phase of neural induction. In contrast to these
      results with Axoloti (urodeles), several authors observed the expression of
      neural specific genes in Xenopus exogastrulae, isolated dorsal blastopore lip
      with adjacent ectoderm (open-face explants) and Keller-sandwiches. Our data with
      Xenopus (anurans) also show that the expression of neural specific genes takes
      place in exogastrulae. However, when we prepared open face explants and
      exogastrula-like structures by microdissection at very early gastrula stage, the
      signal of a class II beta-tubulin, characteristic of terminal neural
      differentiation, is not found in the ectoderm. These results suggest that planar
      signals transmitted from the chordamesoderm into the ectodermal part can fairly
      be excluded under these experimental conditions. In similar experiments with
      Triturus alpestris we could not observe either the differentiation of neural
      structures in the ectodermal part of exogastrulae. These results confirm earlier
      experiments of Holtfreter performed with Ambystoma mexicanum (Axoltl) embryos. On
      the basis of the published data of different authors and our results, we cannot
      exclude the existence of planar signals for early and/or transient expressed
      genes before the onset of gastrulation in Xenopus, which make the neuroectoderm
      susceptible for the response to vertical signals during gastrulation. On the
      other hand our experiments with Triturus alpestris suggest that planar neural
      signals are unlikely in this species. These differences between Triturus and
      Xenopus embryos are discussed in the context of the peculiarities in
      morphological structure, competence and speed of development of the two species.

PMID- 7577444
TI  - In vivo localization of the insulin-like growth factors I and II (IGF I and IGF
      II) gene expression during human lung development.
AB  - The insulin-like growth factors I and II (IGF I and IGF II) are synthesized in
      many organs during human development and are involved in the growth and
      differentiation of tissues. Correlations between lung growth and maturation and
      the local production of IGFs have been poorly explored in humans. Using in situ
      hybridization we localized the synthesis of IGFs in the human fetal respiratory
      tract over an extended period of the gestation and we demonstrated time dependent
      changes. IGF mRNAs were expressed throughout gestation with a clear predominance
      of IGF II and a decreasing expression of both IGFs after the 20th week of
      gestation. They were mainly detected in the mesodermal-derived components of the
      respiratory tract, especially in the undifferentiated mesenchyme of the lung buds
      up to 20 weeks of gestation. At this time the local production of collagen and
      the proliferation of adjacent epithelial cells were predominant features. Later,
      mesenchymal hybridization decreased. Weak epithelial hybridization was observed
      during the first stages of growth and progressively decreased when the epithelium
      underwent maturation: early in the trachea, later in the distal lung buds. A
      consistent expression of IGF II, but not IGF I, in the endothelium, throughout
      gestation, was also observed. The IGFs may act on the near epithelial cell
      proliferation in both autocrine and paracrine ways. They may also stimulate the
      maturation of the connective tissue. This endogenous production of growth factors
      may play a role in the somatic growth during prenatal life.

PMID- 7577446
TI  - Sexual differentiation of reproductive tissue in bivalve molluscs: identification
      of male associated polypeptide in the mantle of Mytilus galloprovincialis Lmk.
AB  - We have addressed the question of sexual reproductive tissue dimorphism in
      bivalve molluscs, Mytilus galloprovincialis Lmk, which is a stable gonochoric
      species although with no apparent differences in gonad morphology of both sexes.
      At all periods of the annual cycle the proteins specific of male/female gonads
      were identified. One of these proteins, "male-associated polypeptide" with
      apparent MW 39 kDa (MAP-39), has been biochemically and immunochemically
      characterized. MAP-39 concentration in male mature gonads achieved up to 10% of
      the total soluble protein while in female ones only traces of this protein could
      be detected. In male mantle, MAP-39 expression was associated with the process of
      gonad development and maturation as well as gamete spawning, although this
      polypeptide has been localized in fibroblast-like cells, membrane of follicles
      and connective tissue matrix of the mantle but not in germinal cells.

PMID- 7577447
TI  - Insulin-like growth factors: the unrecognised oncogenes.

PMID- 7577448
TI  - Cell cycle-dependent cytotoxicity and induction of apoptosis by liposomal N4
      hexadecyl-1-beta-D-arabinofuranosylcytosine.
AB  - The clonogenic growth inhibition, the cell cycle dependence of N4-hexadecyl-1
      beta-D-arabinofuranosylcytosine (NHAC) cytotoxicity and the capability to induce
      apoptosis in ara-C-sensitive and -resistant HL-60 cells were investigated and
      compared with arabinofuranosylcytosine (ara-C). In the clonogenic assay with
      sensitive HL-60 cells, ara-C was slightly more effective than a liposomal
      preparation of NHAC, whereas in the resistant cells, NHAC revealed its potency to
      overcome ara-C resistance, resulting in a 23-fold lower 50% inhibitory
      concentration compared with ara-C. Cell cycle dependent cytotoxicity and
      induction of apoptosis were studied by flow cytometry, using the
      bromodeoxyuridine-propidium iodide and terminal transferase method respectively.
      In contrast to ara-C, NHAC exerted no phase-specific toxicity at low
      concentrations (< 40 microM). At higher concentrations the S-phase-specific
      toxicity increased, probably resulting from ara-C formed from NHAC. NHAC induced
      apoptosis at higher drug concentrations than ara-C, however apoptosis appeared
      not to be limited to the S-phase cells. Apoptosis occurred in both cell lines
      within 2-4 h after drug exposure. These results give further evidence that NHAC
      exerts its cytotoxicity by different mechanisms of action than ara-C and might
      therefore be active in ara-C-resistant tumours.

PMID- 7577449
TI  - Prevention of metastasis from mouse mammary carcinomas with liposomes carrying
      doxorubicin.
AB  - Weekly treatments with doxorubicin encapsulated in long circulating, sterically
      stabilised liposomes (DOX-SL) reduced the incidence of metastases from primary
      mammary carcinoma from 24 of 47 untreated mice to 3 of 23 treated mice. Toxic
      side-effects were limited to minor, transient weight losses.

PMID- 7577451
TI  - Anti-tumour effects of an antibody-carboxypeptidase G2 conjugate in combination
      with phenol mustard prodrugs.
AB  - ADEPT is an antibody-based targeting strategy for the treatment of cancer. We
      have developed two new prodrugs, 4-[N,N-bis(2-chloroethyl)amino]-phenoxycarbonyl
      L- glutamic acid (PGP) and (S)-2-[N-[4-[N,N-bis(2-chloroethyl)amino]-
      phenoxycarbonyl]amino]-4-(5-tetrazoyl)butyric acid (PTP), which are cleaved by
      the bacterial enzyme CPG2 to release the 4-[N,N-bis(2-chloroethyl)amino] phenol
      drug. In vitro, both prodrugs are approximately 100- to 200-fold less potent than
      the parent drug (1 h IC50 = 1.4 microM) in LoVo colorectal tumour cells. These
      prodrugs have been evaluated for utility in ADEPT when used in combination with a
      conjugate of CPG2 and the F(ab')2 fragment of the anti-CEA monoclonal antibody,
      A5B7. The conjugate was shown to localise specifically to established LoVo tumour
      xenografts growing in nude mice and optimal tumour-normal tissue ratios were
      achieved after 72 h. Administration of either prodrug, at doses which cause 6-8%
      body weight loss, 72 h after administration of the A5B7-CPG2 conjugate to the
      LoVo tumour-bearing mice resulted in tumour regressions and growth delays of 14
      28 days. The PTP prodrug in combination with a high dose of conjugate (10 mg kg
      1) gave the best anti-tumour activity despite being a 10-fold worse substrate for
      CPG2 than PGP. Prodrug alone, active drug alone or prodrug in combination with a
      non-specific conjugate had minimal anti-tumour activity in this tumour model.

PMID- 7577450
TI  - Monoclonal antibody Po66 uptake by human lung tumours implanted in nude mice:
      effect of co-administration with doxorubicin.
AB  - The efficacy of radioimmunotherapy of tumours with radiolabelled monoclonal
      antibodies (MAbs) depends on the amount of antibody taken up by the tumour and on
      its intratumoral distribution. In the case of MAbs directed against intracellular
      antigens, increasing the permeability of the cytoplasmic membrane may augment the
      bioavailability of the antigen for the antibody. This raises the question whether
      the induction of tumour necrosis by chemotherapy can enhance the tumour uptake of
      radiolabelled monoclonal antibodies. In this work, the effect of doxorubicin on
      the biodistribution of Po66, an MAb directed against an intracellular antigen,
      was studied in nude mice grafted with the human non-small-cell lung carcinoma
      cell line SK-MES-1. After injection on day 0 of 125I-labelled Po66, tumour
      radioactivity increased up to days 3-5, and then remained unchanged to day 14.
      The combined administration of 125I-labelled Po66 with 8 mg kg-1 doxorubicin, in
      two doses separated by 7 days, doubled the radioactivity retained by the tumour.
      Histological and historadiographic analysis showed, however, that the drug
      induced cellular damage. In the absence of doxorubicin, the accumulation of Po66
      was restricted to some necrotic areas, whereas with doxorubicin the necrosis was
      more extensive and the antibody more evenly distributed. These results suggest
      that chemotherapy and immunoradiotherapy combined would enhance tumour uptake of
      radioisotope and promote more homogenous distribution of the radiolabelled MAb.
      This would promote eradication of the remaining drug-resistant cells in tumours.

PMID- 7577453
TI  - Induction of p53 protein by gamma radiation in lymphocyte lines from breast
      cancer and ataxia telangiectasia patients.
AB  - Exposure of human cells to gamma-radiation causes levels of the tumour-suppressor
      nuclear protein p53 to increase in temporal association with the decrease in
      replicative DNA synthesis. Cells from patients with the radiosensitive and cancer
      prone disease ataxia telangiectasia (AT) exhibit radioresistant DNA synthesis and
      show a reduced or delayed gamma-radiation-induced increase in p53 protein levels.
      We have used Western immunoblotting with semiquantitative densitometry to examine
      the gamma-radiation-induced levels of p53 protein in 57 lymphoblastoid cell lines
      (LCLs) derived from patients with AT, carriers of the AT gene, breast cancer
      patients and normal donors. We confirm the previously reported reduced induction
      in AT homozygote LCLs (n = 8) compared with normal donor LCLs (n = 17, P = 0.01).
      We report that AT heterozygote LCLs (n = 5) also have a significantly reduced p53
      induction when compared with LCLs from normal donors (n = 17, P = 0.02). The
      response of breast cancer patient cells was not significantly different from
      normal donor cells but 18% (5/27) had a p53 response in the AT heterozygote range
      (95% confidence interval) compared with only 6% (1/17) of the normal donor cells.
      We found no significant correlation between p53 induction and cellular
      radiosensitivity in LCLs from breast cancer patients. These methods may be useful
      in identifying individuals at greater risk of the DNA-damaging effects of
      ionising radiation.

PMID- 7577455
TI  - The effect of aminolaevulinic acid-induced, protoporphyrin IX-mediated
      photodynamic therapy on the cremaster muscle microcirculation in vivo.
AB  - The effect of photodynamic therapy on normal striated muscle was investigated
      using 30 adult male rats. Animals were divided into six groups. Three control
      groups received phosphate-buffered saline by gavage and violet light at 105, 178
      and 300 mW cm-2 respectively. Three experimental groups received aminolaevulinic
      acid (ALA; 200 mg kg-1) and violet light at 105, 178 and 300 mW cm-2
      respectively. After exposure of the cremaster muscle animals were allowed to
      equilibrate and vessel diameters and bloodflow assessed. Following
      photoactivation measurements were taken every 10 min over a 2 h period.
      Photoactivation of experimental groups at the two higher power densities resulted
      in an initial decrease in both arteriolar and venular diameters, and a
      concomitant decrease in blood flow. The magnitude of these changes and the degree
      of recovery by the end of the observation period was related to power density. No
      effects were observed in the control groups. These results suggest that
      microcirculatory damage may contribute to the mechanism of action of photodynamic
      therapy with ALA.

PMID- 7577452
TI  - Glutathione determination by the Tietze enzymatic recycling assay and its
      relationship to cellular radiation response.
AB  - Large fluctuations in glutathione content were observed on a daily basis using
      the Tietze enzyme recycling assay in a panel of six human cell lines of varying
      radiosensitivity. Glutathione content tended to increase to a maximum during
      exponential cell proliferation, and then decreased at different rates as the
      cells approached plateau phase. By reference to high-performance liquid
      chromatography and flow cytometry of the fluorescent bimane derivative we were
      able to verify that these changes were real. However, the Tietze assay was
      occasionally unable to detect glutathione in two of our cell lines (MGH-U1 and
      AT5BIVA), although the other methods indicated its presence. The existence of an
      inhibitory activity responsible for these anomalies was confirmed through spiking
      our samples with known amounts of glutathione. We were unable to detect a direct
      relationship between cellular glutathione concentration and aerobic
      radiosensitivity in our panel of cell lines.

PMID- 7577454
TI  - Metabolic imaging in tumours by means of bioluminescence.
AB  - A bioluminescence technique involving single photon imaging was used to quantify
      the spatial distribution of the metabolites ATP, glucose and lactate in
      cryosections of various solid tumours and normal tissue. Each section was covered
      with an enzyme cocktail linking the metabolite in question to luciferase with
      light emission proportional to the metabolite concentration. The photons emitted
      are imaged directly through a microscope and an imaging photon counting system.
      In some cases, good agreement was observed between the distribution of relatively
      high concentrations of ATP and glucose in viable cell regions of the periphery,
      while the reverse was seen in more necrotic tumour centres with comparatively
      high lactate levels. In general, lactate was distributed more diffusely over the
      sections while ATP was more highly localised and glucose assumed an intermediate
      pattern. In contrast to the large degree of heterogeneity seen in tumours,
      distribution patterns of metabolites were much more homogeneous in normal tissue,
      such as heart muscle. Mean values for metabolite levels in cryosections using
      bioluminescence are in good agreement with those obtained from the same tumour by
      conventional methods.

PMID- 7577456
TI  - The mechanisms by which hyperbaric oxygen and carbogen improve tumour
      oxygenation.
AB  - Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing
      the amount of dissolved oxygen in the plasma. That this actually occurs has not
      been verified experimentally. This study was performed to explore changes in
      tumour oxygenation induced by treatment with normobaric and hyperbaric oxygen and
      carbogen. R3230Ac mammary adenocarcinomas were implanted into Fisher 344 rats.
      Arterial blood gases, blood pressure and heart rate were monitored. Tumour
      oxygenation was measured polarographically in five sets of animals. They received
      either normobaric 100% oxygen, hyperbaric (3 atmospheres; atm) 100% oxygen,
      normobaric carbogen or hyperbaric (3 atm) carbogen (HBC) +/- bretylium. HBO
      reduced the mean level of low pO2 values (< 5 mmHg) from 0.49 to 0.07 (P =
      0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001).
      HBC reduced the level of low pO2 values from 0.82 to 0.51 (P = 0.002) an
      increased median pO2 from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and
      carbogen did not change tumour oxygenation significantly. Sympathetic blockade
      with bretylium before HBC exposure improved oxygenation significantly more than
      HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen
      improved tumour oxygenation in this model, while normobaric oxygen or carbogen
      had no effect. Sympathetic-mediated vasoconstriction during hyperbaric carbogen
      caused it to be less effective than HBO. This mechanism also appeared to operate
      during normobaric carbogen breathing.

PMID- 7577457
TI  - Effects of photodynamic therapy on leucocyte-endothelium interaction: differences
      between normal and tumour tissue.
AB  - An inflammatory reaction is regularly noticed in irradiated tissues following
      photodynamic therapy (PDT). This observation is potentially associated with
      leucocyte-mediated tissue damage, which might further contribute to the
      tumoricidal effect of this therapy. The objective of our study was to investigate
      the effects of PDT on leucocyte-endothelium interaction in the microvasculature
      of tumours and normal tissue. Experiments were performed in the dorsal skinfold
      chamber preparation of Syrian golden hamsters bearing amelanotic melanoma A-Mel
      3. The photosensitiser. Photofrin (5 mg kg-1 i.v.) was injected 24 h before laser
      irradiation (630 nm, 100 mW cm-2, 10 J cm-2 or 100 J cm-2). Post-capillary
      confluent venules (diameter 15-40 microns) of subcutaneous (s.c.) tissue or the
      amelanotic melanoma A-Mel-3 were observed by intravital microscopy before, 5, 30,
      60 and 180 min after laser irradiation and recorded for off-line analysis. Before
      treatment, the number of adherent leucocytes in tumour vessels was only 22% of
      the number observed in vessels of s.c. tissue (P < 0.01). The maximum increase in
      adhering leucocytes was observed in post-capillary venules of s.c. tissue 1 h
      after PDT (P < 0.01). In contrast, enhanced leucocyte-endothelium interaction was
      missing in tumour vessels and in control groups. These results indicate that the
      tumour destruction observed after PDT is not mediated by leucocyte-endothelium
      interaction in the tumour. Induction of leucocyte adhesion in the PDT-treated
      normal tissue suggests a contribution to the peritumoral inflammatory response.
      Different maturational status or biochemical properties of tumour microvascular
      endothelium may explain the lack of leucocyte adherence upon PDT.

PMID- 7577458
TI  - Anti-metastatic therapy by urinary trypsin inhibitor in combination with an anti
      cancer agent.
AB  - We have demonstrated that urinary trypsin inhibitor (UTI) purified from human
      urine is able to inhibit lung metastasis of mouse Lewis lung carcinoma (3LL)
      cells in experimental and spontaneous metastasis models. In this study, we have
      investigated whether UTI in combination with an anti-cancer drug, etoposide, can
      prevent tumour metastasis and show an enhanced therapeutic effect. Subcutaneous
      (s.c.) implantation of 3LL cells (1 x 10(6) cells) in the abdominal wall of
      C57BL/6 female mice resulted in macroscopic lung metastasis within 21 days.
      Microscopic lung metastasis was established by day 14 after tumour cell
      inoculation, and surgical treatment alone after this time resulted in no
      inhibition of lung metastasis. The number of lung tumour colonies in the group of
      mice which received surgery at day 21 was greater than in mice which had tumours
      left in situ (P = 0.0017). Surgical treatment on day 7, followed by UTI
      administration (s.c.) for 7 days, led to a decrease in lung metastasis compared
      with untreated animals. A significant inhibition of the formation of pulmonary
      metastasis was obtained with daily s.c. injections of UTI for 7 days immediately
      after tumour cell inoculation. UTI administration did not affect the primary
      tumour size at the time of operation. In addition, etoposide treatment alone led
      to a smaller primary tumours and yielded reduction of the formation of lung
      metastasis in the group of mice which received surgery at day 14 (P = 0.0026).
      Even in mice which received surgical treatment on day 14, followed by the
      combination of UTI (500 micrograms per mouse, days 14, 15, 16, 17, 18, 19 and 20)
      with etoposide (40 mg kg-1, days 14, 18 and 22), there was significant reduction
      of the formation of lung metastasis (P = 0.0001). Thus, the combination of an
      anti-metastatic agent with an anti-cancer drug, etoposide, might provide a
      therapeutically promising basis for anti-metastatic therapy.

PMID- 7577459
TI  - Perturbations of triglycerides but not of cholesterol metabolism are prevented by
      anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma
      (Yoshida AH-130).
AB  - Rats transplanted with the ascites hepatoma Yoshida AH-130 developed a severely
      progressive cachexia, characterised by marked alterations in protein and lipid
      metabolism. In particular, high levels of serum triglycerides and free fatty
      acids were associated with altered levels and distribution of plasma cholesterol,
      with increased total and very low-density lipoprotein-low-density lipoprotein
      (VLDL-LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol.
      The tumour cells showed high rates of cholesterol synthesis and elevated content
      of free and esterified cholesterol, whereas total cholesterol synthesis was
      reduced in the host liver. To determine whether these perturbations could be
      related to the elevation of tumour necrosis factor alpha (TNF-alpha) previously
      shown in the AH-130 bearers (Tessitore L, Costelli P, Baccino FM 1993, Br J
      Cancer, 67, 15-23), either anti-TNF polyclonal antibodies or non-immune IgGs were
      injected daily after tumour transplantation. The anti-TNF treatment neither
      affected tumour growth nor prevented the serum cholesterol changes, while
      attenuating the hypertriglyceridaemia and the elevated serum free fatty acid
      levels. These data indicate that TNF does not appear to be directly involved in
      the altered cholesterol metabolism in AH-130 hosts, thus supporting the view that
      cholesterol metabolism and lipid metabolism are regulated differently during
      tumour growth.

PMID- 7577460
TI  - Importance of P450 reductase activity in determining sensitivity of breast tumour
      cells to the bioreductive drug, tirapazamine (SR 4233).
AB  - P450 reductase (NADPH:cytochrome P450 reductase, EC 1.6.2.4) is known to be
      important in the reductive activation of the benzotriazene-di-N-oxide
      tirapazamine (SR 4233). Using a panel of six human breast adenocarcinoma cell
      lines we have examined the relationship between P450 reductase activity and
      sensitivity to tirapazamine. The toxicity of tirapazamine was found to correlate
      strongly with P450 reductase activity following an acute (3 h) exposure under
      hypoxic conditions, the drug being most toxic in the cell lines with the highest
      P450 reductase activity. A similar correlation was also observed following a
      chronic (96 h) exposure to the drug in air but not following acute (3 h) exposure
      in air. We have also determined the ability of lysates prepared from the cell
      lines to metabolise tirapazamine to its two-electron reduced product, SR 4317,
      under hypoxic conditions using NADPH as an electron donor. The rate of SR 4317
      formation was found to correlate both with P450 reductase activity and with
      sensitivity to tirapazamine, the highest rates of SR 4317 formation being
      associated with the highest levels of P450 reductase activity and the greatest
      sensitivity to the drug. These findings indicate a major role for P450 reductase
      in determining the hypoxic toxicity of tirapazamine in breast tumour cell lines.

PMID- 7577462
TI  - Overexpression of mutant p53 and c-erbB-2 proteins and breast tumour take in
      mice.
AB  - We established a panel of 17 xenografts from primary human breast carcinomas. We
      examined which characteristics of the original tumours and the xenografts
      facilitate growth in animals. Tumours expressing medium or strong
      immunoreactivity for p53 protein had significantly (P < 0.05) higher incidence
      (92%) of in vivo tumour take than those showing weak or negative immunoreactivity
      (9.1%). No such association was observed between either c-erbB-2 or epidermal
      growth factor receptor (EGFR) expression in the original tumours and their in
      vivo tumour take. Following subcutaneous (s.c.) transplantation of original
      breast tumours or established xenografts, 7/17 tumours showed metastatic disease
      spread to distant sites (mainly lungs). This study suggests that selective growth
      of highly aggressive tumours occurs during in vivo propagation of malignant
      tumours, and these tumours will be of particular interest in evaluating various
      chemotherapeutic agents for breast cancer management.

PMID- 7577461
TI  - 8-Chloro-cAMP induces apoptotic cell death in a human mammary carcinoma cell (MCF
      7) line.
AB  - 8-Cl-cAMP and 8-NH2-cAMP induced MCF-7 cell death. The type(s) of cell death were
      studied in more detail and compared with the cell death type (apoptosis) induced
      by okadaic acid, an inhibitor of serine/threonine phosphatases. By morphological
      criteria dying cells showed loss of cell-cell interactions and microvilli,
      condensation of nuclear chromatin and segregation of cytoplasmic organelles. By
      in situ nick end-labelling, using digoxigenin-conjugated dUTP as probe, a large
      fraction of 8-Cl-cAMP, 8-NH2-cAMP and 8-Cl-adenosine-exposed cells stained
      positively in the advanced stages of death. In the early phase of chromatin
      condensation the cells stained negatively. Specific (internucleosomal) DNA
      fragmentation was not observed. The MCF-7 cell death induced by 8-Cl-cAMP and 8
      NH2-cAMP was not mediated by activation of the cAMP kinase since more stable cAMP
      analogues (8-CPT-cAMP and N6-benzoyl-cAMP) or forskolin failed to induce death.
      Furthermore, 8-Cl-cAMP action was counteracted by adenosine deaminase and 3
      isobutyl-1-methylxanthine, and mimicked by 8-Cl-adenosine, a major metabolite of
      8-Cl-cAMP. It is concluded that 8-Cl- and 8-NH2-cAMP can induce morphological and
      biochemical effects resembling apoptotic cell death in MCF-7 cells through their
      conversion into potent cytotoxic metabolite(s).

PMID- 7577464
TI  - Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of
      cachexia and septic shock.
AB  - Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid
      oxidation and muscle protein wasting are common in patients with sepsis, cancer
      or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we
      anticipated that carnitine might promote FA oxidation, thus ameliorating
      metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene
      induced sarcoma models of wasting in rats. In the LPS model, rats were injected
      with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16,
      -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory
      cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the
      sarcoma model, rats were implanted subcutaneously with tumour, and treated
      continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps.
      Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine
      treatment significantly lowered the tumour-induced rise in TG (% rise) in the
      sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine
      groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL
      6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by
      carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs
      222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma
      models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF
      alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups
      respectively. We conclude that carnitine has a therapeutic effect on morbidity
      and lipid metabolism in these disease models, and that these effects could be the
      result of down-regulation of cytokine production and/or increased clearance of
      cytokines.

PMID- 7577463
TI  - Changes in endogenous cytokines, adhesion molecules and platelets during cytokine
      induced tumour necrosis.
AB  - The aim of this study was to investigate mechanisms of anti-tumour activity and
      necrosis induced by combinations of tumour necrosis factor alpha (TNF-alpha) and
      interferon gamma (IFN-gamma). In a breast cancer xenograft model, locally
      injected recombinant human TNF-alpha arrested growth of established tumours in
      the absence of overt necrosis. Macroscopic necrosis occurred when rat IFN-gamma,
      which had no anti-tumour activity as a single agent, was given systemically.
      Treatment with TNF-alpha and IFN-gamma caused focal engorgement of tumour
      capillaries with erythrocytes, intravascular recruitment of polymorphonuclear
      cells and platelet adherence to the tumour vascular endothelium 4 h after the
      combined treatment. This was followed by destruction of tumour vascular
      endothelium and both necrosis and apoptosis of tumour cells. Concomitant with
      these changes, semiquantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) analysis revealed the increase of stromal (murine) mRNA levels for TNF
      alpha, TNF receptor 55 kDa, TNF receptor 75 kDa, intracellular adhesion molecule
      1, vascular cell adhesion molecule 1, P-selectin and interleukin 6 (IL-6). Thus,
      the effect of the combined TNF-alpha and IFN-gamma therapy involved the selective
      destruction of the tumour vasculature, death of tumour cells and increased
      expression of a series of stromal cytokines, cytokine receptors and adhesion
      molecules, which could be implicated in the observed events.

PMID- 7577465
TI  - Allelotype of squamous cell carcinoma of the head and neck: fractional allele
      loss correlates with survival.
AB  - Allelic imbalance or loss of heterozygosity (LOH) studies have been used
      extensively to identify regions on chromosomes that may contain putative tumour
      suppressor genes. We have undertaken an extensive allelotype of 80 specimens of
      squamous cell carcinoma of the head and neck (SCCHN) using 145 polymorphic
      microsatellite markers on 39 chromosome arms. Allelic imbalances were found most
      frequently on chromosome arms 3p, 9p, 17p and 18q with over 45% LOH and
      imbalances on 1p, 1q, 2p, 5q, 6p, 6q, 8p, 8q, 9q, 11q, 13q, 17q and 19q were
      found in more than 20% of SCCHN. These LOH data were analysed against a range of
      clinicopathological parameters which included previously untreated and previously
      treated tumours; correlations were found between LOH on 9q and nodes at pathology
      (P = 0.02) and between histopathological grade and LOH on 12q (P = 0.02) and 13q
      (P = 0.01). In the group of previously untreated tumours, a correlation was found
      between site of tumour and LOH on 3p (P = 0.019), and 8p (P = 0.029), while TNM
      staging correlated with LOH on 3p (P = 0.019) and 17p (P = 0.016). Fractional
      allele loss (FAL) was calculated for 52 tumours with LOH data on nine or more
      chromosomal arms and found to have a median value of 0.22 (range 0.0-0.80).
      Correlations were found between FAL > median value and nodes at pathology (P =
      0.01) and tumour grade (P = 0.06), demonstrating that advanced tumours with lymph
      node metastasis often had LOH at multiple sites. FAL > median value was found to
      correlate with a poor survival (P < 0.03) and, furthermore, FAL > median value
      correlated with poor survival in the previously untreated patients (P < 0.019).
      These results indicate that assessment of the accumulation of genetic damage, as
      provided by allelotype data, provides a useful molecular indicator of the tumour
      behaviour and clinical outcome.

PMID- 7577467
TI  - Evaluation of the significance of polyamines and their oxidases in the aetiology
      of human cervical carcinoma.
AB  - The risk of cancer of the cervix is linked with sexual behaviour. Although
      infectious agents such as human papillomaviruses (HPVs) are implicated, these
      alone may be insufficient to induce the disease. We have investigated the
      potential role of oxidation products of the polyamines spermine and spermidine
      and the diamine putrescine in seminal plasma (SP) as co-factors in the
      development of cervical cancer. These amines are oxidised by polyamine oxidase
      (PAO) and diamine oxidase (DAO) to generate oxygen radicals and hydrogen
      peroxide, reactive aldehydes and acrolein, which are likely to exert local
      mutagenic, cytotoxic and immunosuppressive effects in vivo. Using a
      chemiluminescence assay, we determined the levels of these amines in 187 samples
      of SP. Spermine plus spermidine, as substrates for PAO, were present in a range
      equivalent to 0-4.8 mg ml-1 spermine. Putrescine, as a substrate for DAO, was
      detectable in only 4 of 40 samples assayed (range 0-168 micrograms ml-1) and
      constitutes a minor component of the oxidisable content of SP. Cervical mucus
      (126 samples) was assayed for the presence of PAO and DAO. Both enzymes were
      present in 14.3% of the samples, PAO only in 21.4%, DAO only in 15.1% and neither
      enzyme in 49.2%. PAO levels ranged from 0 to 0.828 pmol peroxide generated min-1
      mg-1 mucus and DAO levels ranged from 0 to 7.0 pmol peroxide generated min-1 mg-1
      mucus. These results suggest that sexual activity in the absence of physical
      barrier contraception may lead to the generation of mutagenic and
      immunosuppressive polyamine oxidation products within the female genital tract.
      We thus propose that women with high levels of PAO and/or DAO in their cervical
      mucus may be at increased risk of cervical cancer, especially if the male
      partner's SP shows high polyamine levels. HPV infection may synergise with the
      effects of polyamine oxidation by suppressing apoptosis in keratinocytes carrying
      potentially oncogenic mutations, leading to the survival and proliferation of
      transformed cells in the cervix.

PMID- 7577466
TI  - Mammary cancer in transgenic mice expressing insulin-like growth factor II (IGF
      II)
AB  - The effect of insulin-like growth factor II (IGF-II) on tumour development in the
      mouse mammary gland was studied. To promote extra IGF-II expression in the
      mammary gland, sheep beta-lactoglobulin regulatory elements were attached to the
      coding regions of the mouse Igf-2 gene and injected into the pronuclei of mouse
      zygotes. Mammary tumours developed in each of the four independent lines of mice
      which expressed transgene IGF-II in the gland. Tumours from two of the lines grew
      after transplantation to both male and female hosts. Primary tumours contained
      stromal and epithelial regions, but the tumours were dominated by mammary
      adenocarcinoma after transplantation. The tumours expressed high levels of Igf-2
      mRNA transcribed from the integrated transgenes.

PMID- 7577468
TI  - Establishment of two new scirrhous gastric cancer cell lines: analysis of factors
      associated with disseminated metastasis.
AB  - Determination of the differences between cell lines which are derived from a
      primary tumour and a disseminated metastatic lesion from the same patient may aid
      in elucidating the factors associated with disseminated metastases. We report on
      the establishment and characterisation of two new scirrhous gastric cancer cell
      lines, designated OCUM-2M and OCUM-2D, derived from a 49-year-old female. OCUM-2M
      was derived from a primary gastric tumour, and OCUM-2D was derived from a sample
      of disseminated metastasis. The two cell lines were derived from the same
      patient. We investigated biological differences between the two cell lines to
      study mechanisms involved in disseminated metastasis. The growth activity of OCUM
      2D cells as determined by doubling time and tumorigenicity was greater than that
      of OCUM-2M cells. The level of epidermal growth factor receptor (EGFR) expression
      in OCUM-2D cells was about twice that of OCUM-2M cells and the growth of OCUM-2D
      cells was stimulated more by epidermal growth factor (EGF) than that of OCUM-2M
      cells. The invasive activity of OCUM-2D cells was higher than that of OCUM-2M
      cells and was increased after addition of transforming growth factor-beta 1 (TGF
      beta 1). An increase in the number of attached and spreading cells was found
      following the addition of 10 ng ml-1 TGF-beta 1. These findings suggest that high
      growth and invasive activity may play an important role in disseminated
      metastasis and that EGF and TGF-beta 1, which affect the growth and invasive
      activity of OCUM-2D cells, might be factors associated with metastasis in
      scirrhous gastric carcinoma. The two cell lines OCUM-2M and OCUM-2D should be
      beneficial for analysing mechanisms of tumour progression.

PMID- 7577469
TI  - Molecular and immunohistochemical analysis of P53 in phaeochromocytoma.
AB  - We searched for mutations of the p53 gene in 25 phaeochromocytomas using
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      analysis of the entire conserved region of the gene, encompassing exons 4-8;
      expression of the p53 protein was assessed by immunohistochemistry. No mutations
      were found, while a polymorphism in codon 72 was observed. Immunohistochemistry
      revealed nuclear p53 overexpression in one tumour sample. We conclude that
      mutations of the 'hotspot' region of the p53 gene do not seem to play a role in
      the pathogenesis of phaeochromocytoma.

PMID- 7577471
TI  - A novel styryl diphenylamine derivative reverts the transformed phenotype of
      human fibrosarcoma HT1080 cells.
AB  - Revertant cells, which can be isolated from transformed cells, are flat, non
      transformed variants that have contributed to the elucidation of mechanisms
      involved in cell transformation. We have discovered that a novel styryl
      diphenylamine derivative converts human fibrosarcoma HT1080 cells into revertant
      cells. This compound induces flat cell morphology and causes a decrease in
      proliferative rate. The flat revertant cells not only exhibit a reduction in
      saturation density at confluence, but also lose the ability to proliferate in
      soft agar. Furthermore, their tumorigenicity is reduced when injected s.c. into
      athymic nude mice. The compound alters morphology in three out of seven cancer
      cell lines and has a potent growth inhibitory effect in six of these lines. In
      contrast, it has only low levels of cytotoxicity for three normal diploid cell
      lines. These findings indicate that this styryl diphenylamine derivative has the
      potential to suppress the malignant phenotype of cancer cells without profound
      cytotoxicity in non-transformed cells.

PMID- 7577472
TI  - Redundancy of autocrine loops in human rhabdomyosarcoma cells: induction of
      differentiation by suramin.
AB  - Three human rhabdomyosarcoma cell lines were used to investigate the presence of
      autocrine loops based on the production of insulin-like growth factor (IGF)-II,
      basic fibroblast growth factor (bFGF) and epidermal growth factor
      (EGF)/transforming growth factor (TGF)-alpha and of their corresponding
      receptors, and whether these loops affect cell proliferation and myogenic
      differentiation. Two cell lines, RD/18 and CCA, deriving from tumours of the
      embryonal histotype, showed the presence of both growth factors and receptors
      which make possible three different autocrine loops, while the alveolar RMZ-RC2
      cell line lacked that based on the EGF receptor. Culture of rhabdomyosarcoma
      cells in the presence of specific blocking antibodies, directed to a component of
      single autocrine loops, inhibited cell proliferation (up to 50%), without
      inducing myogenic differentiation. Suramin, a drug which non-selectively
      interferes with the binding of growth factors to their cellular receptors, was
      used to block all the autocrine loops simultaneously. In CCA and RMZ-RC2 cells
      suramin was able to induce a significant increase (up to 3-fold) in the
      proportion of myosin-positive cells over control cultures. Therefore
      rhabdomyosarcoma cells of embryonal and alveolar histotype can show a redundancy
      of growth-sustaining autocrine loops. Suramin could interfere with them by acting
      on both growth inhibition and induction of myogenic differentiation.

PMID- 7577470
TI  - Loss of cyclin-dependent kinase inhibitor genes and chromosome 9 karyotypic
      abnormalities in human bladder cancer cell lines.
AB  - Loss of cell cycle control through the structural or functional aberration of
      checkpoint genes and their products is a potentially important process in
      carcinogenesis. In this study, a panel of well-characterised established human
      bladder cancer cell lines was screened by the polymerase chain reaction for
      homozygous loss of the cyclin-dependent kinase inhibitor genes p15, p16 and p27.
      The results demonstrate that, whereas there was no genetic loss of p27,
      homozygous deletion of both p15 and p16 genes occurred in seven of 13 (54%)
      independent bladder cell lines tested. Differential loss of either the p15 or p16
      gene was not seen. The p15 and p16 genes are known to be juxtaposed on chromosome
      9p21 at the locus of a putative tumour-suppressor gene involved in the initiation
      of bladder cancer. Cytogenetic analysis of the cell lines revealed karyotypes
      ranging from near diploid to near pentaploid with complex rearrangements of some
      chromosomes and a high prevalence of chromosome 9p rearrangements, although all
      cell lines contained at least one cytogenetically normal 9p21 region. These
      observations support a role for p15/p16 gene inactivation in bladder
      carcinogenesis and/or the promotion of cell growth in vitro and lend support to
      the hypothesis that homozygous deletion centred on 9p21 is a mechanism by which
      both p15 and p16 genes are co-inactivated.

PMID- 7577473
TI  - Multiple polymorphisms, but no mutations, in the WAF1/CIP1 gene in human brain
      tumours.
AB  - The cyclin kinase inhibitor WAF1/CIP1, also termed CDKN1, mediates p53-induced
      cell cycle arrest in response to DNA damage. This property makes it an attractive
      tumour-suppressor candidate for a p53-associated tumour-suppressor gene. In order
      to investigate the role of WAF1/CIP1 in the pathogenesis of primary human brain
      tumours we performed single-stranded conformation polymorphism (SSCP) analysis
      and direct sequencing of exon 2 of the gene in a representative series of 158
      brain tumours and corresponding blood samples. In addition, all tumours were
      examined for mutations in exons 5-8 of the p53 gene. Analysis of WAF1/CIP1
      revealed multiple polymorphisms, the most abundant being AGC-->AGA (Ser-->Arg) at
      codon 31 with an allele frequency of 8.5%. Less common polymorphisms included GTG
      ->GGG (Val-->Gly) at codon 25, GCC-->ACC (Ala-->Thr) at codon 64, CGC-->CTC (Arg-
      >Leu) at codon 32, GGC-->AGC (Gly-->Ser) at codon 14 and GCG-->GTG (Ala-->Val) at
      codon 39 each with an allele frequency of 0.3%. These polymorphisms were all
      located in a conserved region of exon 2. Two of the polymorphisms were also seen
      in a group of 157 healthy controls indicating that WAF1/CIP1 polymorphisms do not
      predispose to cancer. None of the tumours included in our series showed a somatic
      mutation in WAF1/CIP1. All samples were also analysed for loss of heterozygosity
      on the short arm of chromosome 6 in the region of the WAF1/CIP1 locus. Allelic
      loss was observed in only one patient with a glioblastoma. Mutations in the p53
      gene were found in 22 of 158 tumours. No association was found between any
      polymorphism of the WAF1/CIP1 gene, p53 mutations and histopathological tumour
      type. Our data indicate that WAF1/CIP1 mutations are probably not involved in the
      formation of primary human brain tumours.

PMID- 7577475
TI  - Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on
      chromosome 13q12-q13.
AB  - Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of breast tumours.
      This may reflect the inactivation of the retinoblastoma susceptibility gene RB1.
      However, recently another candidate tumour-suppressor gene has been identified on
      chromosome 13 by linkage analysis, the breast cancer susceptibility gene BRCA2.
      To investigate the involvement of BRCA2 in sporadic breast cancer 200 breast
      tumours were tested for LOH on chromosome band 13q12-q14, using 11 highly
      polymorphic microsatellite markers. LOH was found in 65 tumours, which all showed
      simultaneously loss of BRCA2 and RB1. Of 12 breast tumour cell lines tested with
      polymorphic microsatellite markers, seven showed a contiguous region of
      homozygosity on 13q12-q14, suggesting LOH in the tumour from which the cell line
      had been derived. One cell line showed homozygosity in the BRCA2 region and
      heterozygosity at RB1. This is the only indication that BRCA2 is a distinct
      target for LOH on chromosome 13 in addition to RB1.

PMID- 7577474
TI  - Hprt mutants in a transplantable murine tumour arise more frequently in vivo than
      in vitro.
AB  - A model system was developed to allow investigation of the frequency at which
      clastogenic and/or mutagenic events occur in situ in a transplantable murine
      fibrosarcoma tumour (MC1A-C1) compared with in vitro culture. The marker selected
      for detecting these events was the X-linked hprt (hypoxanthine-guanine
      phosphoribosyltransferase) gene. We found that the hprt gene in MC1A-C1 was not
      suitable for this purpose, most likely because multiple active copies were
      present. To circumvent the problem, HPRT- [6-thioguanine (6-TG)-resistant] clones
      were isolated by inactivating all hprt genes with methylnitrosourea. Spontaneous
      revertants to hypoxanthine/aminopterin/thymidine resistance (HATR) were isolated
      and found to be approximately 1000 times more sensitive than the parental tumour
      to induction of 6-TGR mutants by cobalt-60 gamma-rays. This sensitivity is
      expected for a heterozygous marker, these revertants may therefore possess only
      one functional hprt locus but two or more active X chromosomes. A clone with a
      stable hprt gene was identified and a neo gene was introduced. The resulting cell
      line (MN-11) could be grown as a subcutaneous tumour in syngeneic C57BL/6
      animals. The frequency of mutations arising in vivo in the marker hprt gene could
      be estimated by culturing explanted tumour cells in the presence of 6-TG, using
      G418 selection to distinguish tumour from host cells. The frequency of mutants in
      MN-11 cells grown as tumours was found to be 3.4-fold higher than in tissue
      culture for an equivalent period of time. These data provide the first direct
      evidence for the existence of mutagenic factors in a tumour environment that
      might contribute to tumour progression.

PMID- 7577476
TI  - Laevofolinic acid, 5-fluorouracil, cyclophosphamide and escalating doses of
      epirubicin with granulocyte colony-stimulating factor support in locally advanced
      and/or metastatic breast carcinoma: a phase I-II study of the Southern Italy
      Oncology Group (GOIM).
AB  - Sixty-four consecutive patients with locally advanced (n = 7) or metastatic
      breast cancer (n = 57), were treated with a combination of laevofolinic acid 100
      mg m-2 plus 5-fluorouracil 340 mg m-2 i.v. on days 1-3, cyclophosphamide 600 mg m
      2 i.v. on day 1 and epirubicin 90 mg m-2 i.v. on day 1. Epirubicin dose was
      progressively escalated by 10 mg m-2 per cycle up to 120 mg m-2 in the absence of
      dose-limiting toxicities. Granulocyte colony-stimulating factor (G-CSF) was given
      subcutaneously in order to prevent neutropenia. Epirubicin dosage could be
      increased to 100 mg m-2 in 53 patients (87%), to 110 mg m-2 in 31 patients (51%)
      and to 120 mg m-2 in 18 cases (30%). In most patients the dose-limiting toxicity
      was represented by myelosuppression. A statistically significant correlation was
      found between median white blood count (WBC) or absolute neutrophil count (ANC)
      nadir and epirubicin dose level (P = 0.009; P = 0.008). Moreover, a statistically
      significant correlation was observed between the number of chemotherapeutic
      cycles, nadir ANC and WBC and the occurrence of anaemia and thrombocytopenia of
      increasing severity. These data suggest the occurrence of progressive cumulative
      bone marrow toxicity. Although patients who reached different epirubicin levels
      showed differences in mean dose intensity, such differences were not
      statistically significant. No correlation was found between the increase in dose
      intensity and type, rate or duration of objective responses. In patients with
      metastatic breast cancer the overall response rate was 72% (95% CL 66-78%) with a
      25% complete response rate. Median duration of response was 10 and 13 months
      respectively for complete and partial responses. All patients with locally
      advanced breast cancer had an objective response and underwent radical
      mastectomy. Projected median survival of the whole series of patients with
      metastatic breast cancer was 20 + months. These data demonstrate that the
      combination of 5-fluorouracil with laevofolinic acid, cyclophosphamide and
      epirubicin is very active against metastatic breast cancer. Use of G-CSF allows
      epirubicin dosage to be increased up to 120 mg m-2 cycle-1, but its use may be
      linked to the occurrence of sometimes severe cumulative haematological toxicity.

PMID- 7577477
TI  - Long-term follow-up of elderly patients with operable breast cancer treated with
      surgery without axillary dissection plus adjuvant tamoxifen.
AB  - Between 1982 and 1990, 321 elderly patients (range 70-92 years, median age 77)
      with operable breast cancer (T1 in 219, T2 in 77, T3 in one and T4b in 24
      patients) and clinically uninvolved axillary nodes underwent surgery without
      axillary dissection and received adjuvant tamoxifen. All patients had surgery
      performed under local anaesthesia. Tamoxifen was given after surgery at the dose
      of 20 mg daily, indefinitely. With a median follow-up of 67 months (range 42
      141), 17 patients developed local relapse, 14 ipsilateral axillary recurrence,
      five ipsilateral breast cancer, five contralateral breast cancer, 13 second
      primary and 23 developed distant metastases. The cumulative probability of
      developing a local, axillary and distant recurrence at 72 months was estimated to
      be 5.4%, 4.3% and 6.2%, respectively. Out of 244 patients who did not develop any
      relapse, 83 (25.8%) died from intercurrent disease. The 72 month relapse-free
      survival rate was 76%. This experience suggests that elderly patients with small
      tumours without clinical axillary involvement may be satisfactorily treated with
      conservative surgery and tamoxifen. The importance of axillary dissection is
      controversial owing to a high response rate to hormonal therapy and an increased
      death rate due to concomitant diseases.

PMID- 7577478
TI  - A phase II study of carboplatin and vinorelbine as second-line treatment for
      advanced breast cancer.
AB  - Forty-one patients with advanced breast cancer were given carboplatin and
      vinorelbine as second-line therapy. Overall objective response rate was 46% (95%
      confidence interval 26-56%). Myelotoxicity was the most frequently observed toxic
      effect; grade III-IV leucopenia occurred in 46% of the patients. Our regimen is
      active as second-line chemotherapy for advanced breast cancer and warrants
      further evaluation.

PMID- 7577480
TI  - Phase II trials of rhizoxin in advanced ovarian, colorectal and renal cancer.
AB  - Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of
      murine tumour models. The recommended schedule, of intravenous (i.v.) bolus
      administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three
      phase II trials of ovarian, renal and colorectal cancer. In general terms the
      drug was fairly well tolerated, but the response rate was disappointing: 0/18,
      colorectal cancer; 0/18, renal cancer; 1 partial response (PR)/17, ovarian
      cancer.

PMID- 7577481
TI  - Diagnostic and therapeutic approaches to lung cancer in Canada and their costs.
AB  - Escalating health care costs have made it imperative to evaluate the resources
      required to diagnose and treat major illnesses in Canadians. For Canadian men,
      lung cancer is not only the most common malignancy, but also the major cancer
      killer. As of 1994, lung cancer is expected to overtake breast cancer as the
      leading cause of cancer deaths in women. This paper presents a detailed
      description of the methodology used to determine the direct health care costs
      associated with 'standard' diagnostic and therapeutic approaches for lung cancer
      in Canada in 1988. Clinical algorithms were developed for each stage of non-small
      cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The algorithms were
      designed to take the form of decision trees for each clinical stage of lung
      cancer. The proportion of patients assigned to each branch was based upon
      questionnaire responses obtained from thoracic surgeons and radiation oncologists
      when presented with clinical scenarios, and information from provincial cancer
      registries. Direct care costs were derived primarily from one provincial fee
      schedule (Ontario), and costing information obtained during the conduct of
      several Canadian clinical trials in lung cancer. Direct costs for diagnosis and
      initial treatment of NSCLC (excluding relapse and terminal care costs) ranged
      from $17,889 for the surgery/post-operative radiotherapy arm of stages I and II
      to $6,333 for the supportive care arm (stage IV). The cost of determining relapse
      for NSCLC was estimated to be $1,528, and terminal care costs, which included
      palliative radiotherapy and hospitalisation, were $10,331. Direct costs for
      diagnosis and initial treatment of SCLC ranged from $18,691 for limited stage
      disease to $4,739 for the supportive care arm of extensive disease. The cost of
      diagnosing relapse for SCLC was estimated to be $1,590, and terminal care costs
      averaged $9,966. This report provides an estimate of the Canadian costs of
      managing lung cancer by stage and treatment modality. Because the actual costs of
      all components of care are not available from any combination of sources, these
      cost estimates must be viewed as an idealised estimate of the cost of lung cancer
      management. However, we believe that the lung cancer costing model that we have
      developed provides a level of sophistication which gives a reasonable estimate of
      the cost per case of treating NSCLC and SCLC.

PMID- 7577479
TI  - Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to
      first line hormonal therapy.
AB  - Several oncogenes and tumour-suppressor genes have been identified that may have
      an important role in the development of human breast carcinoma. Furthermore, some
      of these gene alterations may be linked to the development of invasion and
      subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2
      have all been linked to tumours with rapid cellular proliferation, but the
      evidence that they are of prognostic importance in patients with breast cancer is
      conflicting. This study explores the relationship between expression of these
      oncoproteins and clinical outcome in 92 patients with either locally advanced or
      metastatic breast cancer treated with primary endocrine therapy. Specimens of the
      primary carcinoma were available for analysis of hormone receptor, Ki67 labelling
      index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21.
      Clinical response was measured according to UICC criteria after 6 months of
      treatment and all patients were followed for time to progression and overall
      survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67
      labelling index and EGFR overexpression were associated with a shorter time to
      progression and overall survival. However, no statistically significant
      relationship existed between expression of ras p21, p53 or c-erbB-2 and response
      to treatment, time to progression or overall survival. We conclude that staining
      for these three oncoproteins has no role in therapeutic decision-making in
      patients with advanced breast cancer. The negative finding implies that while
      abnormal expression of these genes may have an important role in the development
      of breast cancer, the variations in growth characteristics of advanced breast
      cancer may be influenced by other factors.

PMID- 7577482
TI  - Differences in treatment and survival rates of non-small-cell lung cancer in
      three regions of France.
AB  - Treatment and survival rates of patients with non-small-cell lung cancer (NSCLC)
      were compared between three French Cancer Registries (Calvados, Doubs, Tarn). The
      methodological issues in such comparisons are discussed. The treatments for NSCLC
      differed between the regions: radiotherapy tended to be preferred in Calvados
      (73% vs 21.3% surgery), whereas surgery was more frequently employed in Doubs and
      Tarn (27.7% and 37% respectively). The percentage of cases receiving no
      therapeutic treatment ranged from 7.8% (Calvados) to 26% (Tarn). Despite the
      differences in treatment, the overall survival rates were similar in the three
      regions. Adjustment for treatment in such a descriptive study may be misleading
      since different therapeutic strategies in different regions may lead to selection
      of patients of systematically better or poorer prognosis in the various treatment
      groups.

PMID- 7577484
TI  - A randomised double-blind comparison of intravenous pamidronate and clodronate in
      the hypercalcaemia of malignancy.
AB  - In conjunction with rehydration, the bisphosphonates are the treatment of choice
      for hypercalcaemia of malignancy. Single infusions of either pamidronate or
      clodronate are usually effective, but a direct comparison of the two agents given
      at the highest doses commonly used has not been performed. Forty-one patients (15
      breast, 12 squamous carcinomas, four lymphomas, four bladder, two prostate and
      four others) with hypercalcaemia of malignancy (corrected serum calcium > 2.7
      mmol l-1) persisting after 48 h of saline rehydration were randomly allocated to
      receive a 4 h intravenous (i.v.) infusion of either pamidronate 90 mg or
      clodronate 1500 mg. No other systemic anti-cancer treatment was prescribed. There
      were no significant differences in the post-hydration serum calcium values (mean
      3.17 mmol l-1 for pamidronate and 3.06 mmol l-1 for clodronate), tumour type or
      frequency of bone metastases between the two treatments. One patient on each
      treatment died within 2 days and was not assessable for response. A total of
      19/19 (100%) patients achieved normocalcaemia following pamidronate and 16/20
      (80%) with clodronate. The median time to achieve normocalcaemia was 4 days
      (range 2-14) for pamidronate and 3 days (range 2-6) with clodronate. The median
      duration of normocalcaemia was 28 days (range 10-28+ days) after pamidronate and
      14 days after clodronate (range 7-21 days) (P < 0.01). Two patients who failed to
      respond to clodronate were successfully treated with pamidronate and achieved
      normocalcaemia for 14 and > 28 days respectively. Two patients experienced fever
      after pamidronate but no significant toxicity was observed with either treatment.
      We conclude that both agents are effective in the management of hypercalcaemia of
      malignancy. At the doses studied, the effects of pamidronate are more complete
      and longer lasting than those of clodronate.

PMID- 7577486
TI  - Referral patterns within Scotland to specialist oncology centres for patients
      with testicular germ cell tumours. The Scottish Radiological Society and the
      Scottish Standing Committee of the Royal College of Radiologists.
AB  - Details of 1123 patients registered in Scotland between 1983 and 1990 for
      testicular cancer under the Scottish Cancer Registration Scheme were obtained and
      compared with registrations within the five Scottish oncology centres. Some
      registration discrepancies were identified. Twenty-eight cancer registrations
      (2.5%) were coded to the wrong site, 29 patients seen at oncology centres had no
      cancer registration and 14 cancer registrations had the wrong histology. Five
      hundred and twenty-seven patients with testicular non-seminomatous germ cell
      tumours (NSGCT) and 567 with testicular seminoma were identified. Referral rates
      to specialist oncology centres for testicular germ cell tumours were measured by
      period and health board area of residence. For the whole study period 92% of
      NSGCT and 93% of seminoma patients were referred to specialist centres for
      treatment. Referral rates for different health board areas of residence were not
      significantly different. This study shows that within Scotland the majority of
      patients with testicular NSGCT and seminoma are referred to specialist centres,
      and suggests referral rates of around 92% are underestimates. Access is not
      related to area of residence.

PMID- 7577483
TI  - Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I
      II study.
AB  - Twenty-three patients with pleural mesothelioma stage I-IIA were entered in a
      study of continuous daily intrapleural infusion of interleukin 2 (IL-2) for 14
      days, repeated every 4 weeks. IL-2 was administered according to a groupwise dose
      escalation schedule (group A, 3 x 10(4); group B, 3 x 10(5); group C, 3 x 10(6);
      group D, 6 x 10(6); group E, 18 x 10(6); and group F, 36 x 10(6) IU day-1). Each
      group consisted of at least three patients. Intrapleural administration of IL-2
      was associated with acceptable toxicity. All patients were treated on an
      outpatient basis except for the patients at dose levels E and F. Dose-limiting
      toxicity was observed at level F, 36 x 10(6) IU daily, and consisted of catheter
      infection, fever and flu-like symptoms. Intrapleural IL-2 levels were high (>
      20,000 IU ml-1) at levels E and F, while serum levels in most patients were not
      or barely detectable (< 3-30 IU ml-1). Intrapleural IL-2 levels were up to 6000
      fold higher than systemic levels. Intrapleural tumour necrosis factor alpha (TNF
      alpha) levels varied greatly and did not correlate with IL-2 dosage. Intrapleural
      mononuclear cells (MNCs) displayed IL-2-induced lymphokine-activated killer (LAK)
      activity in all patients. Two patients were not evaluable for response owing to
      catheter-related problems which precluded the delivery of IL-2. Partial response
      (PR) occurred in 4 of 21 evaluable patients (19%; 95% confidence interval 5-42%)
      with a median time to progression of 12 months (range 5-37). Stable disease (SD)
      occurred in seven patients with a median time to progression of 5 months (range 2
      7). There were no complete responses (CRs). The median overall survival was 15.6
      months (range 3.0-43). No relationship between the dose of IL-2 and response rate
      was observed. We conclude that IL-2 given intrapleurally is accompanied with
      acceptable toxicity and has anti-tumour activity against mesothelioma. In view of
      the refractory nature of the disease IL-2 may be a treatment option for
      mesothelioma. A formal phase II study is warranted. Based on the observed
      toxicity, the lack of dose-response relationship and the immunomodulatory effects
      seen at relatively low-dose IL-2, the recommended dose for a phase II study is 3
      x 10(6) IU day-1 using the present treatment schedule.

PMID- 7577488
TI  - A Scottish national mortality study assessing cause of death, quality of and
      variation in management of patients with testicular non-seminomatous germ-cell
      tumours. The Scottish Radiological Society and the Scottish Standing Committee of
      the Royal College of Radiologists.
AB  - A detailed casenote review was performed on 55 patients registered with
      testicular non-seminomatous germ cell tumours (NSGCT) between 1983 and 1988 under
      the Scottish Cancer Registration Scheme and who had died by 1992. Details of all
      aspects of clinical management relating to their NSGCT and death details were
      extracted and summarised. An assessment was made on whether the patients'
      management had been optimal. An analysis of 5 year survival rates by the five
      Scottish oncology centres demonstrated significant differences between centres
      (range 70.4-94.2; chi 2 = 14.46, d.f. = 4, P = 0.006). Some patients in all
      centres were assessed as having received suboptimal treatment, but two centres
      performed less well than the other three. There is a suggestion that the number
      of patients treated suboptimally decreases with increasing number of patients
      seen, but this does not reach statistical significance.

PMID- 7577487
TI  - A Scottish national audit of current patterns of management for patients with
      testicular non-seminomatous germ-cell tumours. The Scottish Radiological Society
      and the Scottish Committee of the Royal College of Radiologists.
AB  - A detailed casenote review was performed on all 65 patients registered with
      testicular non-seminomatous germ cell tumours (NSGCT) during 1989 under the
      Scottish Cancer Registration Scheme. Details of management at presentation and 2
      years following diagnosis were recorded and analysed. In a small number of
      patients an unacceptable delay in diagnosis was noted. Variation was found in the
      frequency and type of investigations performed on patients placed on
      surveillance, types of chemotherapy regimens used and numbers of patients entered
      into trials. Three per cent of patients had a biopsy of the contralateral testis
      and 27% of patients defaulted from clinic attendance. Considerable variation in
      the management of testicular NSGCT in Scotland has been identified. The
      introduction of management guidelines should result in a more consistent approach
      to the care of these patients. Support, both financial and psychological, may
      reduce the unacceptable rate of default.

PMID- 7577485
TI  - Cyclosporin A and doxorubicin-ifosfamide in resistant solid tumours: a phase I
      and an immunological study.
AB  - In order to test whether circumvention of clinical resistance can be obtained in
      common solid tumours by targeting different drug resistance mechanisms, a phase I
      clinical and immunological study was designed. The purpose of the study was to
      determine the dose of cyclosporin A (CsA), in combination with doxorubicin (DOX)
      and ifosfamide (IFX), needed to achieve steady-state whole-blood levels of 2000
      ng ml-1 and the associated toxicity of this combination. Treatment consisted of
      CsA 5 mg kg-1 as a 2 h loading infusion, followed by a CsA 3 day continuous
      infusion (c.i.) (days 1-3) at doses that were escalated from 10 to 18 mg kg-1 day
      1. Chemotherapy consisted of DOX 55 mg m-2 by i.v. 24 h c.i. (day 2) and IFX 2 g
      m-2 i.v. over 1 h on days 1 and 3. Treatments were repeated every 4 weeks.
      Eighteen patients with previously treated resistant solid tumours received 39
      cycles. Mean steady-state CsA levels > or = 2000 ng ml-1 were reached at 5 mg kg
      1 loading dose followed by a 3 day c.i. of 16 mg kg-1 day-1 or greater.
      Haematological toxicity was greater than expected for the same chemotherapy
      alone. One patient died of intracranial haemorrhage due to severe thrombopenia.
      Other observed toxicities were: asymptomatic hyperbilirubinaemia (46% cycles),
      mild nephrotoxicity (20% cycles), hypomagnesaemia (72% cycles), mild increase in
      body weight (100% cycles), hypertension (15% cycles) and headache (15% cycles).
      Overall the toxicity was acceptable and manageable. No alterations in absolute
      lymphocyte number, the lymphocyte subsets studied (CD3, CD4, CD8, CD19) or
      CD4/CD8 ratio were observed in patients receiving more than one treatment cycle,
      although there were significant and non-uniform variations in the values of the
      different lymphocyte subsets studied when pre- and post-treatment values were
      compared. There was also a significant increase in the CD4/CD8 ratio. Tumour
      regressions were observed in two patients (epidermoid carcinoma of the cervix and
      Ewing's sarcoma). The CsA dose recommended for phase II trials is a 5 mg kg-1
      loading dose followed by a 3-day c.i. of 16 mg kg-1 day-1 simultaneously with DOX
      and IFX at the doses administered in this study.

PMID- 7577489
TI  - Cancer mortality in Indian and British ethnic immigrants from the Indian
      subcontinent to England and Wales.
AB  - Risk of cancer mortality from 1973 to 1985 in persons born in the Indian
      subcontinent who migrated to England and Wales was analysed by ethnicity, and
      compared with cancer mortality in the England and Wales native population, using
      data from England and Wales death certificates. There were substantial highly
      significant raised risks in Indian ethnic migrants for cancers of the mouth and
      pharynx, gall bladder, and liver in each sex, larynx and thyroid in males, and
      oesophagus in females. There were also substantial raised risks in these migrants
      of each sex for non-Hodgkin's lymphoma and myeloma. For the mouth and pharynx,
      and liver in each sex, and gall bladder in females, there were also raised risks
      of lesser magnitude in British ethnic migrants. For colon and rectal cancer and
      cutaneous melanoma in each sex, ovarian cancer in women and bladder cancer in
      men, there were appreciable significantly reduced risks in the Indian ethnic
      migrants not shared by those of British ethnicity. Appreciable raised risks in
      British ethnic migrants not shared by those of Indian ethnicity occurred for
      nasopharyngeal cancer in males, soft tissue malignancy in both sexes and non
      melanoma skin cancer in males. In migrants of both ethnicities there were
      appreciable significantly raised risks in each sex for leukaemia and decreased
      risks in each sex for gastric cancer, for lung cancer except in females of
      British ethnicity and in males for testicular cancer. The results suggest the
      need for public health measures to combat the high risks of oral and pharyngeal
      cancers and liver cancer in the Indian ethnic immigrant population of England and
      Wales, by prevention of betel quid chewing and hepatitis transmission
      respectively. The data also imply that early exposures or early acquired
      behaviours in India, or exposures during migration, may increase the risk of
      leukaemia and reduce the risks of gastric and testicular cancers in the migrants
      irrespective of their ethnicity. Aetiological studies would be worthwhile to
      investigate the reasons for the sizeable decreased risk of colon and rectal
      cancer and increased risk of gall bladder cancer in each sex and the increased
      risk of thyroid and laryngeal cancer in males and oesophageal cancer in females
      of Indian ethnicity but not of British ethnicity who have migrated from the
      Indian subcontinent.

PMID- 7577490
TI  - The effect of family size on estimates of the frequency of hereditary non
      polyposis colorectal cancer.
AB  - Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is currently
      based on phenotypical analysis of an expanded pedigree. Diagnostic guidelines
      ('Amsterdam criteria') proposed by the International Collaborative Group on HNPCC
      are often too stringent for use with small families. There is also the
      possibility of false-positive diagnosis in large pedigrees that may contain
      chance clusters of tumours. This study was conducted to determine the effect of
      family size on the probability of diagnosing HNPCC according to the Amsterdam
      criteria. A total of 1052 patients with colorectal cancer were classified as
      HNPCC or non-HNPCC according to the Amsterdam criteria. Associations between this
      diagnosis and the size of the first-degree pedigree were evaluated in logistic
      regression and linear discriminant analyses. Logistic regression showed a
      significant association for family size with the Amsterdam-criteria-based HNPCC
      diagnosis. Linear discriminant analysis showed that HNPCC diagnosis was most
      likely to occur when first-degree pedigrees contained more than seven relatives.
      Failure to consider family size in phenotypic diagnosis of HNPCC can lead to both
      under- and overestimation of the frequency of this disease. Small pedigrees must
      be expanded to reliably exclude HNPCC. Positive diagnoses based on assessment of
      eight or more first-degree relatives should be supported by other clinical
      features.

PMID- 7577493
TI  - p53 mutations in human papillomavirus-associated oesophageal squamous cell
      carcinoma.

PMID- 7577491
TI  - Expression and prognostic significance of Bcl-2 in ovarian tumours.
AB  - The expression of bcl-2 was studied in normal ovaries and in ovarian tumours by
      immunohistochemical analysis. Normal epithelium was strongly stained in all nine
      examined ovaries. In comparison, all tumour groups showed a substantially
      decreased tumour cell expression of the same order of magnitude. Thus, benign
      tumour cells were weakly stained in two and unstained in two samples, while the
      remaining eight showed strong expression. Of ten borderline samples, one was
      unstained and five had weakly and four strongly bcl-2 positive tumour cells.
      Finally, 24 of 50 malignant tumours showed strong staining, while weak or no
      expression in tumour cells was found in 16 and 10 samples respectively. The
      reduced staining deviated significantly from normal ovary for both borderline (P
      = 0.02) and malignant groups (P = 0.01). Tumour cell staining with the bcl-2
      antibody was significantly reduced when tumour mass had to be left behind
      compared with those with no visible remaining tumour (P = 0.03 and 0.003 for
      weakly and strongly stained tumours respectively). The expression of bcl-2 in
      malignant tumour cells was inversely correlated with the expression of p53. Bcl-2
      expression was correlated with survival with significantly reduced survival in
      weakly (P = 0.02) and unstained (P < 0.001) groups compared with those patients
      having strongly stained malignant tumour cells. This correlation between the
      presence of bcl-2 and survival was maintained in the subgroups of patients with
      advanced disease or with residual tumour bulk and was also the case in patients
      having p53-positive tumours. Our results indicate an inhibitory role of bcl-2 in
      development and progression of ovarian tumours.

PMID- 7577494
TI  - New era for education.

PMID- 7577492
TI  - Molecular genetic evidence for unifocal origin of advanced epithelial ovarian
      cancer and for minor clonal divergence.
AB  - Detection of loss of heterozygosity (LOH) and DNA flow cytometry (FCM) were used
      to trace the origin of bilateral ovarian cancer from 16 patients. From each
      tumour the DNA index (DI) and LOH patterns for chromosomes 1, 3, 6, 11, 17, 18,
      22 and X were determined with 36 microsatellite markers. Formalin-fixed, paraffin
      embedded as well as frozen specimens were used. Flow cytometric cell sorting was
      used to enrich tumour cells for polymerase chain reaction (PCR)-driven LOH
      analysis. Analysis of the LOH data showed that in 12 of the 16 cases concordance
      was observed for all informative markers, namely retention of heterozygosity
      (ROH) or loss of identical alleles in both tumour samples. In four cases
      discordant LOH patterns were observed. In two cases the discordant LOH was found
      for one of the chromosomes tested while other LOH patterns clearly indicated a
      unifocal origin. This suggests limited clonal divergence. In the other two cases
      all LOH patterns were discordant, most likely indicating an independent origin.
      The number of chromosomes showing LOH ranged from 0 to 6. Comparison of DNA FCM
      and the LOH data showed that the latter technique has a higher sensitivity for
      the detection of a unifocal origin. In 14/16 cases evidence was found for a
      unifocal origin, while in two cases clonal divergence was found at LOH level and
      in two other cases clonal divergence at DNA ploidy level. In 12 cases the
      complete observed allelotype had developed before the formation of metastases,
      including the two cases showing a large DNA ploidy difference.

PMID- 7577495
TI  - Market testing still on a small scale.

PMID- 7577496
TI  - Lowest morale ever.

PMID- 7577497
TI  - Assessing neonatal pain.

PMID- 7577499
TI  - Mind your language.

PMID- 7577498
TI  - Living in interesting times.

PMID- 7577500
TI  - Care of urinary catheters.

PMID- 7577501
TI  - The NHS and its future.

PMID- 7577502
TI  - Helping children with challenging behaviour.
AB  - Last year's reports from the Audit Commission and Mental Health Foundation (1, 2)
      have highlighted the extreme vulnerability of children with learning disabilities
      who also present severe challenging behaviour. The author outlines the findings
      of the latter report and emphasises the role nurses can play in protecting and
      caring for such children.

PMID- 7577503
TI  - Quality assurance in a nursing home.
AB  - The private nursing home sector must be accountable to its consumers and staff.
      This article describes an initiative to canvas the views of residents' next of
      kin and care staff as a basis for quality assurance mechanisms. The authors
      describe the process, its results and the changes in care provision which have
      been brought about.

PMID- 7577505
TI  - Mental illness can damage your career.

PMID- 7577506
TI  - An exhausting route to a large overdraft.

PMID- 7577504
TI  - One minute wisdom.

PMID- 7577508
TI  - AIDS focus. Food for thought.

PMID- 7577507
TI  - AIDS focus. The great dilemma.

PMID- 7577510
TI  - Education on eczema.

PMID- 7577509
TI  - Danger in local authority commissioning.

PMID- 7577511
TI  - Ready for government?. Interview by John Naish.

PMID- 7577513
TI  - The personal touch.

PMID- 7577512
TI  - Caring for special clients.

PMID- 7577514
TI  - Occupational health: dealing with stress.
AB  - This article describes the role of the occupational health nurse in identifying
      and managing employee health problems caused by stress. The author emphasis the
      need for collaboration between employer and employee in a relationship mediated
      by the nurse.

PMID- 7577517
TI  - Bionursing: diabetes in elderly patients.
AB  - Bionursing is a series of 12 articles looking at how biological theories should
      integrate with practice. In the fourth article, the authors describe the case
      study of an elderly, bereaved woman suffering from incontinence and lack of
      motivation. They argue that with a physical assessment, the woman's underlying
      problem of diabetes mellitus would have been diagnosed earlier.

PMID- 7577518
TI  - The changing role of the nurse teacher.
AB  - The training of nurses has changed significantly in recent years, as have the
      role and expectations of nurse teachers and lecturers. In this article, the
      author suggests the development of a new role which could satisfy the
      requirements of educators, clinicians and students.

PMID- 7577515
TI  - Do nurses care for patients any more?

PMID- 7577516
TI  - In vitro fertilisation: a study of clients waiting for pregnancy test results.
AB  - The aim of this study was to obtain a descriptive account of clients' perceptions
      of the delay between embryo transfer and pregnancy test. The clients' responses
      were collected using a structured interview. The study sample comprised 15
      couples, and the interviews took place on day 28 (or 13 days after embryo
      transfer) of the in vitro fertilisation (IVF) cycle, before the outcome of
      treatment was known. The study identified the 'wait at home' interlude between
      embryo transfer and pregnancy test as the most stressful aspect of treatment.
      Clients' responses indicated that adequate provision of information, contact with
      the IVF team and a specified nurse responsible for their care, may have benefited
      some couples during this time. The conclusion was that although the sample size
      was small, it comprised a pilot study which could be replicated in several
      centres. The recommendations made on the basis of the results include an advice
      sheet pertinent to this waiting time, the adoption of primary nursing and the
      development of nursing intervention to provide emotional support. This may help
      to ameliorate the isolation felt by couples during this delay.

PMID- 7577519
TI  - A necessity not a choice.

PMID- 7577520
TI  - Training to empower people.

PMID- 7577521
TI  - Reinforcing an autumn ritual.

PMID- 7577523
TI  - Spot the difference.

PMID- 7577522
TI  - Watching for change: being breast aware.

PMID- 7577524
TI  - Call to involve nurses in reorganisation.

PMID- 7577525
TI  - No support for students.

PMID- 7577526
TI  - Hoping the worst storms are over.

PMID- 7577527
TI  - A service second to none.

PMID- 7577529
TI  - Voluntary service. Capital calls.

PMID- 7577528
TI  - Contraceptive services. An enhanced role and a better service.

PMID- 7577530
TI  - Practice development units: progress update.
AB  - Following a previous Nursing Standard article about the Seacroft Hospital
      practice development unit (1), this article describes the progress which has been
      made since. The author describes some of the problems the unit has encountered,
      explains how staff have managed change and analyses the implications for the PDU
      model which have arisen from those developments.

PMID- 7577531
TI  - Social psychology in group therapy practice.
AB  - This article describes a social psychology approach to group therapy. Using a
      short case study, the author suggest the options for treatment which are
      available to the therapist and reasons why treatment based on social psychology
      offers a unique therapeutic potential.

PMID- 7577532
TI  - There is a new and healthy drive in the NHS to ensure that research underpins all
      activity.

PMID- 7577534
TI  - The role of CPNS. Piggy in the middle.

PMID- 7577536
TI  - Standards can help morale.

PMID- 7577533
TI  - Epilepsy.

PMID- 7577535
TI  - Damaging drugs.

PMID- 7577539
TI  - Assisting the surgeon: the dilemma for nurses.

PMID- 7577537
TI  - Theatre nursing. Looking to the future.

PMID- 7577538
TI  - Agent for change.

PMID- 7577541
TI  - Making a stand for nurses.

PMID- 7577542
TI  - Finding a path to improved services.

PMID- 7577543
TI  - Ready for the challenge. Interview by Jean Gray.

PMID- 7577544
TI  - A break with tradition.

PMID- 7577545
TI  - Comparable work, unequal earnings.

PMID- 7577540
TI  - Imaging the liver.

PMID- 7577546
TI  - Pharmacology in the bionursing model.
AB  - In the third article in our series on bionursing, the authors again focus on the
      integration of theory and practice. In this case, they emphasise the need for
      nurses to understand the pharmacology of medications as a facet of bionursing.

PMID- 7577547
TI  - Achieving a 3 per cent pay award.

PMID- 7577548
TI  - Putting vocational training into practice.

PMID- 7577549
TI  - The patient handover: a study of its form, function and efficiency.
AB  - This study investigates the nature of the ward handover report. It was undertaken
      following observations that student nurses seemed not to receive enough knowledge
      to care for patients in an informed way. Data were gathered through participant
      observation on two busy medical wards over a period of two weeks. The data
      revealed a complex system of communication was necessary to allow nurses to
      provide continuity of care for patients in a safe manner. The handover was seen
      as working effectively but with scope for improvement. It was often long, lasting
      up to 60 minutes, and its information so comprehensive that it was difficult to
      assimilate in one session. It was found to be a process of variable quality due
      to the lack of supporting framework. The findings are discussed and
      recommendations are made to improve the handover's quality and effectiveness.

PMID- 7577550
TI  - Uniting services in tissue viability care.
AB  - This article shows how two new NHS trusts are striving to provide a seamless
      service to their populations while maintaining their own identities. With the
      appointment of a clinical nurse specialist in tissue viability, the trusts are
      providing a more cost-effective and efficient service and are more willing to
      communicate and co-operate with each other.

PMID- 7577551
TI  - Emily's last days.

PMID- 7577552
TI  - Using memories.

PMID- 7577554
TI  - Occupational hazards.

PMID- 7577553
TI  - Making their minds up.

PMID- 7577555
TI  - The long and the short of it.

PMID- 7577556
TI  - Coming home?

PMID- 7577557
TI  - Challenging depression.

PMID- 7577558
TI  - Iron: keeping in the red.

PMID- 7577559
TI  - Prediction and qualitative assessment of five- and six-year-old children's
      reading: a longitudinal study.
AB  - This paper describes a longitudinal study comparing the power of two screening
      batteries (that of Clay, 1979, and that of a set of tests of phonological
      awareness and sound-to-letter correspondence knowledge) to identify, in the first
      term at school, children at risk of failing to learn to read successfully. A
      single test from one of the batteries is shown to provide an adequate screening
      procedure. There is no significant gain in predictive power if screening is
      delayed until the end of the first year at school. Regarding processes of the
      screened children are investigated at the end of their first year in school, and
      again seven months later. Almost all the best readers can use some phonological
      recoding processes by the end of their first year at school. Seven months later,
      this is true of all the best readers, with children who had now learned to use
      phonological recoding processes showing greater gains in reading age than those
      who had not.

PMID- 7577560
TI  - Cognitive and motivational determinants of academic achievement and behaviour in
      third and fourth grade disadvantaged children.
AB  - While most studies on the determinants of learning deal with either cognition or
      motivation, there is a growing awareness that both should be considered. Our
      purpose was to examine the relative roles of cognitive and motivational factors
      for the scholastic achievement and behaviour of disadvantaged children. Cognition
      was conceptualised in terms of the psychosemantic theory that assesses cognitive
      processes by characteristics of the individual's meaning assignment (Kreitler &
      Kreitler, 1987a). Motivation was conceptualised in terms of the cognitive
      orientation (CO) theory which assumes that cognitive contents guide behaviour
      (Kreitler & Kreitler, 1982). Participants were 57 third and fourth graders of
      both genders, recommended for a remedial summer programme. They were administered
      the Meaning Test assessing cognitive abilities; the CO Questionnaire of
      Motivation for Learning assessing the disposition to learn; and the Metropolitan
      Achievement Test and the IOWA tests assessing verbal, mathematical and working
      skills. Teachers completed the Teacher-Child Rating Scale assessing six
      scholastic behaviours. Regression analyses showed that all dependent variables
      were predicted by the cognitive and motivational variables, better by specific
      than global predictors. Cognitive variables contributed more to the predictions,
      especially of academic achievements, and more in the case of verbal than
      mathematical abilities. In girls, motivational factors played a larger role than
      cognitive factors, absolutely and relative to boys. Implications for promoting
      scholastic achievements are discussed.

PMID- 7577561
TI  - Development of scales to measure perceived physical education class climate: a
      cross-national project.
AB  - Motivational research in the classroom has adopted a social cognitive perspective
      but has mainly been restricted to the study of individual achievement cognitions.
      In addition to this, there is a need to study and assess the perception children
      have of the class climate. Using social cognitive theory as a base, this research
      reports the development of class climate scales in French and English for use in
      physical education classes. Psychometric development with the French scale was
      shown to be satisfactory, including adequate factorial structure assessed by
      exploratory and confirmatory factor analysis (CFA), and good internal and test
      retest reliability. A parallel English scale demonstrated a less adequate fit to
      the proposed model when using CFA, but shortened scales assessing just mastery
      and performance dimensions of climate were shown to predict important
      motivational measures in a structural equation modelling analysis.

PMID- 7577562
TI  - [Growth determination in the premature using knemometry].

PMID- 7577563
TI  - [Dying and death--how to deal with it? Theme of a seminar].

PMID- 7577564
TI  - [Ambulatory pediatric surgery--characteristics, concept and results after 25.000
      interventions].

PMID- 7577565
TI  - [Ambulatory surgery--from the viewpoint of the day-care nurse].

PMID- 7577566
TI  - [Help in adjustment to an oncologic pediatric department].

PMID- 7577567
TI  - [Psychosocial attendance from the viewpoint of the hospital chaplain].

PMID- 7577568
TI  - [Poisonous and less poisonous plants. 19].

PMID- 7577569
TI  - [Obligation of nursing insurance].

PMID- 7577570
TI  - [Federal Work Group Child and Hospital--results of a statewide study].

PMID- 7577571
TI  - [Personal contact meeting of the continuing education course "Nursing
      administration in the Hospital"--restructuring of ambulatory and inpatient
      nursing].

PMID- 7577572
TI  - [Bottle feeding for infants--comments to the article "Bottle Feeding for Infants"
      by Wiltrud Martin in issue 6/95, page 251 of "Kinderkrankenschwester"].

PMID- 7577573
TI  - [Nutrition during the 1. Year of life. Requested comment on the letter by Marlene
      Schmidt and on the article by Wiltrud Martin, issue 6/1995, page 251 in
      Kinderkrankenschwester].

PMID- 7577574
TI  - The 9th annual North American Cystic Fibrosis Conference. Dallas, Texas, October
      12-15, 1995. Abstracts.

PMID- 7577575
TI  - Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis
      in vivo and in vitro.
AB  - Keratinocyte differentiation in psoriasis was examined using a panel of
      monospecific monoclonal antibodies to keratins (K), including two recently
      developed monoclonal antibodies raised to carboxy terminal peptides of K6 (LL020)
      and K16 (LL025). Keratinocytes from normal skin, untreated psoriatic plaques and
      non-lesional psoriatic skin, were cultured using multiple in vitro systems. Time
      lapse cinephotography was used to measure the intermitotic time of normal and
      psoriatic keratinocytes in both low calcium-defined and serum-containing media.
      The intermitotic time did not differ significantly between psoriatic and normal
      keratinocytes. Keratin expression of psoriatic and normal keratinocytes in vitro
      was examined by both gel electrophoresis and immunocytochemistry. K6, K16 and K17
      were detected suprabasally in all culture systems in vitro, but only in
      interfollicular psoriatic epidermis in vivo, and not in normal skin. Small
      subpopulations of keratinocytes expressed simple epithelial keratins K7, K8, K18
      and K19 in cultures on plastic substrates, but these keratins were absent in skin
      equivalents of normal or psoriatic skin. No psoriasis-specific pattern of
      differentiation was found in vitro. As the K6 peptide antibody reacted with basal
      cells of normal skin, probably due to K5 cross-reactivity, K16 expression
      determined by LL025 was found to be the most sensitive indicator of the psoriatic
      state of differentiation, and this antibody is recommended for future work on
      psoriasis. K17 had a distinct pattern of tissue distribution in normal skin: K17,
      but not K16, was present in basal myoepithelial cells in sweat glands, and the
      deep outer root sheath, but K17 distribution paralleled that of K16 in suprabasal
      psoriatic epidermis. As keratins K6, K16 and K17 are expressed in keratinocyte
      hyperproliferation, when high levels of certain cytokines are also expressed, the
      role of growth factors and regulatory nuclear transcription factors in the
      control of K6, K16 and K17 expression in psoriasis requires further study, in
      order to provide insight into the relationship between proliferation and
      differentiation.

PMID- 7577577
TI  - Demonstration of antibodies to bovine desmocollin isoforms in certain pemphigus
      sera.
AB  - We have shown previously that IgG antibodies in certain pemphigus sera,
      particularly endemic Brazilian pemphigus foliaceus (BPF) sera, react with bovine
      desmocollins (Dsc), which are transmembranous glycoproteins of desmosome
      junctions. Desmocollins occur as three different isoforms (Dsc 1, 2 and 3), all
      of which are represented in the epidermis. In this study, we examined sera of
      various pemphigus types by immunoblotting purified bovine desmosomes and bovine
      Dsc 1, 2 and 3 fusion proteins, expressed in pGEX expression vectors. Six of 15
      (40.0%) BPF sera, two of 18 (11.1%) non-endemic pemphigus foliaceus sera, eight
      of 39 (20.5%) pemphigus vulgaris (PV) sera, and two of 11 (18.2%) normal sera,
      showed reactivity with Dsc from desmosomes. Experiments with fusion proteins
      showed that no Dsc isoform was specifically recognized by sera of any individual
      pemphigus type. Our results indicate that the pathogenesis of pemphigus might be
      more complex than previously believed.

PMID- 7577578
TI  - The in vivo melanocytotoxicity and depigmenting potency of N-2,4-acetoxyphenyl
      thioethyl acetamide in the skin and hair.
AB  - It has been shown previously that N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP)
      is a tyrosinase substrate and a potent depigmenting agent of dark skin and black
      hair. The present study evaluated the depigmenting potency of an acetyl
      derivative of N-Ac-4-S-CAP, N-2,4-acetoxyphenyl thioethyl acetamide (NAP-TEA) in
      the skin and hair. We tested for (i) in vitro metabolites in the skin after
      topical application, and (ii) in vivo depigmenting potency in the skin and hair.
      We found that NAP-TEA was stable in water, but was converted to N-Ac-4-S-CAP
      after topical application to human skin. Therefore, although NAP-TEA was not a
      tyrosinase substrate, it could react with tyrosinase after being converted to N
      Ac-4-S-CAP by O-deacetylation in vivo. NAP-TEA produced marked depigmentation of
      dark skin (Yucatan pig) after daily topical application. When given by
      intraperitoneal injection, it resulted in complete loss of hair colour (white)
      grown at the epilated site in adult C57 black mice after daily administration for
      10 days, and incomplete loss of coat colour (silver grey) in newborn C57 black
      mice after a single administration. The depigmentation of the skin and hair was
      reversible. Split-dopa preparation and electron microscopy indicated that this
      depigmentation is primarily related to (i) a marked decrease in the number of
      functioning melanocytes and melanized melanosomes, (ii) a decrease in the number
      of melanosomes transferred to keratinocytes, and (iii) selective
      degeneration/inactivation of melanocytes, and deposition of melanin-like material
      in the Golgi cisternae, coated vesicles and melanosomes, where tyrosinase is
      reported to be located. We propose the NAP-TEA is converted in vivo to N-Ac-4-S
      CAP which, via interaction with tyrosinase, causes reversible depigmentation of
      the skin and hair.

PMID- 7577579
TI  - Adherence of Malassezia isolates to human keratinocytes in vitro--a study of HIV
      positive patients with seborrhoeic dermatitis.
AB  - Adherence of Malassezia yeast cells to human keratinocytes was assessed by a
      novel technique using double-sided Sellotape. Although adherence using double
      sided Sellotape is still merely a model for in vivo adherence, it approximates to
      the conditions found on the skin surface. There were no differences in adhesive
      properties to human keratinocytes between Malassezia strains originating from HIV
      positive and HIV-negative patients with seborrhoeic dermatitis, nor was there a
      relationship between the severity of seborrhoeic dermatitis and in vitro
      adherence to human keratinocytes.

PMID- 7577576
TI  - Abnormalities of serum type III procollagen aminoterminal peptide in methotrexate
      treated psoriatic patients with normal liver histology do not correlate with
      hepatic ultrastructural changes.
AB  - In a previous study, it was shown that the serum levels of type III procollagen
      aminoterminal peptide (P3NP) were significantly greater in patients receiving
      methotrexate (MTX) treatment for psoriasis than in untreated control patients
      with psoriasis. Although levels were highest in patients with hepatic fibrosis
      and cirrhosis, serum P3NP concentrations in those patients with normal liver
      histology on light microscopy were also shown to be significantly higher than in
      controls. In the present study, liver biopsies from 22 such 'normal' patients
      were examined by electron microscopy, in order to determine whether P3NP levels
      correlated with ultrastructurally demonstrable fibrosis. Fibrosis in the
      perisinusoidal space of Disse was present in as many as 82% of biopsies. Although
      the prevalence of such fibrosis in psoriasis patients who have not received MTX
      is unknown, the high prevalence of Disse space fibrosis and of raised P3NP in MTX
      treated patients suggests that MTX causes subtle liver damage in a majority of
      treated patients. However, we were unable to show a statistical correlation
      between P3NP and the degree of Disse space fibrosis.

PMID- 7577580
TI  - Detection of Epstein-Barr virus in cutaneous and lymph nodal anaplastic large
      cell lymphomas (Ki-1+).
AB  - Epstein-Barr virus (EBV) is a gamma DNA herpes virus which is thought to play a
      part in the pathogenesis of some non-Hodgkin's lymphomas in individuals with or
      without immunodeficiency. We investigated 16 lymph nodal and 12 cutaneous
      anaplastic large cell lymphomas (ALCLs) (Ki-1+), all of which were in patients
      without immunodeficiency, for the presence of EBV genomes. The highly sensitive
      polymerase chain reaction (PCR) technique was employed for detection of viral DNA
      in extracts from formalin-fixed, paraffin-embedded tissue sections. In addition,
      we performed radioactive and non-radioactive in situ hybridization (ISH) for
      localization of EBV at the single cell level. EBV-DNA was demonstrated by PCR in
      five cases of nodal ALCLs (31%). All cutaneous ALCLs were negative. EBV-encoded
      small nuclear RNAs (EBERs) could be identified by ISH in the tumour cells of one
      of the five EBV-DNA-positive patients. Our results further support the concept
      that EBV may be involved in the development of a proportion of nodal ALCLs, but
      not in cutaneous ALCLs.

PMID- 7577581
TI  - Two novel mast cell phenotypic markers, monoclonal antibodies Ki-MC1 and Ki-M1P,
      identify distinct mast cell subtypes.
AB  - In order to identify more specific or selective mast cell markers, the reactivity
      of two monoclonal antibodies, Ki-MC1 and Ki-M1P, was studied by
      immunohistochemistry in two human cell lines (mast cell line HMC-1, basophilic
      cell line KU812), in mast cells cultured from blood precursors, in adherent
      mononuclear cells from peripheral blood, and in mast cells of tissue sections
      from 13 urticaria pigmentosa lesions, five mastocytomas and five normal skin
      specimens. Toluidine blue staining, fluorescence staining with FITC-conjugated
      avidin, and immunohistochemical staining (APAAP) with other mast cell reactive
      monoclonal antibodies, was performed for comparison. Double staining with the
      APAAP method, using the Ki-antibodies and toluidine blue, was also carried out.
      Both Ki-antibodies showed reactivity for skin mast cells, but with a different
      staining pattern. In addition, the Ki-MC1 antibody did not react with the cell
      lines, and reacted only with a few peripheral blood mononuclear cells and
      cultured mast cells. In contrast, the Ki-M1P antibody reacted with almost all
      cultured mast cells and blood mononuclear cells, but stained only about one-half
      of lesional and one-fifth of normal skin mast cells. Ki-M1P also reacted with
      many toluidine blue-negative dermal cells, particularly in urticaria pigmentosa.
      Ki-MC1 antibody can thus be considered as a useful additional marker for normal
      skin mast cells. In contrast, the Ki-M1P antibody primarily identifies immature
      mast cells and monocytes/macrophages, suggesting that these cell types probably
      originate from the same bone marrow precursor.

PMID- 7577582
TI  - Merkel cells do not require trophic maintenance from the nerves in adult human
      skin.
AB  - A 34-year-old Japanese man with hereditary sensory neuropathy was examined to
      evaluate the distribution, density and inter-relationship between Merkel cells
      and peripheral nerves in the skin. An epidermal sheet of affected plantar skin
      showed numerous CAM 5.2-reactive Merkel cells, whereas PGP 9.5-reactive
      peripheral nerves were completely absent in the epidermis and dermis. These
      findings strongly suggest that Merkel cells do not require trophic maintenance
      from nerves in adult human skin.

PMID- 7577583
TI  - Aneuploidy in actinic keratosis and Bowen's disease--increased risk for invasive
      squamous cell carcinoma?
AB  - The value of DNA single cell cytometry for the detection of aneuploidy was
      assessed in 100 specimens of actinic keratoses and 39 specimens of Bowen's
      disease. Ten seborrhoeic keratoses and 10 samples of normal epidermis served as
      negative control groups. Monolayer smears, prepared from formalin-fixed, paraffin
      embedded tissues, were Feulgen-stained and used for interactive DNA-cytometry. In
      each specimen, the DNA content of 150 randomly chosen squamous epithelial cells
      was measured, using a TV-image analysis system (TAS-plus, Leica, Germany).
      Aneuploidy was diagnosed if at least three nuclei with a DNA content above 5c
      (5cEE > or = 3) were found. The aneuploidy rate in actinic keratosis was 69% (69
      of 100) and in Bowen's disease was 95% (37 of 39). Another 20 specimens of
      actinic keratoses and the remaining two specimens of Bowen's disease were
      diagnosed as suspicious for aneuploidy (0 < 5cEE < 3). The 20 specimens of
      seborrhoeic keratoses and normal epidermis did not show any nuclei above the 5c
      level, and were classified as non-aneuploid. This indicates a sensitivity of 76%
      (106 of 139) and a specificity of 100% (20 of 20). The frequent occurrence of
      aneuploidy in actinic keratoses and Bowen's disease underlines the character of
      the lesions as epidermal carcinomas in situ, but does not explain the long-term
      low incidence of invasive growth.

PMID- 7577584
TI  - Sweat secretion, stratum corneum hydration, small nerve function and pruritus in
      patients with advanced chronic renal failure.
AB  - Sweat secretion, stratum corneum hydration and small nerve fibre function were
      measured in 40 patients with advanced chronic renal failure (CRF), using
      pilocarpine iontophoresis, electrical capacitance and a thermal sensory analyser
      which measures the thresholds of warm and heat pain sensation. Correlations were
      sought between these parameters, and the presence and severity of pruritus and
      skin xerosis were compared with 45 healthy control subjects. The mean sweat
      secretion and stratum corneum hydration of CRF patients were significantly lower
      than in controls. Thirteen patients had pathological thresholds to warm sensation
      on the foot, and eight on the hand. None had pathological thresholds to heat
      pain. The presence of pruritus did not correlate with any of the following:
      xerosis, stratum corneum hydration, sweat secretion or the results of thermal
      testing.

PMID- 7577585
TI  - The use of video image analysis for the measurement of venous ulcers.
AB  - The accurate measurement of the size of skin wounds and ulceration is important
      for comparing the efficiency of treatment modalities and for monitoring progress
      in the individual patient. Although various methods of differing sophistication
      are in use, many of the common simpler techniques lack accuracy and reliability.
      We describe a new technique of ulcer measurement which uses video image
      recording, capture and computer analysis. A method of correcting for limb
      convexity in a two-dimensional image is presented. The method has an overall
      accuracy of 1.82% and a clinical precision of 3.41%, both of which are
      significantly better than acetate tracings or photographic methods. The technique
      is simple and rapid, and once established it incurs minimal ongoing costs.

PMID- 7577586
TI  - Venous leg ulcers and squamous cell carcinoma: a large-scale epidemiological
      study.
AB  - In order to obtain a precise estimate of the relative risk of squamous cell
      carcinoma (SCC) in venous leg ulcers, we matched 10,913 patients with the
      diagnosis venous leg ulcer from the Swedish Inpatient Registry with registrations
      of SCC of the lower limb recorded by the Swedish Cancer Registry, and found 33
      cases of non-melanoma skin cancer. After scrutinizing the pathology and case
      records, 17 cases of SCC were considered as being certainly secondary to venous
      leg ulcers, whereas in six cases of remitting/relapsing ulcers the connection was
      probable. The relative risk calculated on 17 cases was 5.80 (95% confidence
      interval = 3.08-9.29). The median duration of the ulcer before the diagnosis of
      cancer was 25 years. The mean follow-up time of the cohort was 8.5 years. We
      conclude that SCC is a complication of chronic venous leg ulcers, although the
      absolute risk is very small.

PMID- 7577587
TI  - Dermatology in-patient management greatly improves life quality.
AB  - The aim of this study was to measure the effect of in-patient management on the
      quality of life of adult dermatology patients, and to identify the diagnostic
      categories which show the greatest improvement. Over a 6-month period, all 230
      patients admitted to the dermatology ward of the University Hospital of Wales
      were invited to complete a Dermatology Life Quality Index (DLQI) questionnaire on
      admission, and again 4 weeks after discharge. Two hundred and seventeen (93%) of
      these patients entered the study, and 181 (83.4%) returned both questionnaires.
      The mean DLQI on admission was 13.2 (standard deviation [SD] 7.6; n = 181), and 4
      weeks after discharge it was 7.7 (SD 6.8; P < 0.001). Seventy-three per cent of
      the 181 patients showed improvement, 5.5% remained unchanged, and 21.5% worsened.
      Patients with psoriasis improved from 13.7 (SD 6.5) to 6.7 (SD 5.6; n = 63; P <
      0.001), and those with eczema improved from 16.2 (SD 6.3) to 9.6 (SD 7.6; n = 56;
      P < 0.001). Patients with pruritus showed little improvement, as did those
      admitted for liver biopsy. Patients with psoriasis and severe eczema showed,
      overall, a significant decrease in impairment of life quality following in
      patient treatment. Severe eczema has a greater adverse impact on the quality of
      life than severe psoriasis. The parameters for which most improvement was seen
      were those which were of most concern to the patients, i.e. their symptoms (score
      after discharge = 1.2; DS 0.9; P < 0.001) and their embarrassment (0.9; SD 1.0; P
      < 0.001).

PMID- 7577588
TI  - Correlation of the clinical manifestations and gene mutations of Japanese
      xeroderma pigmentosum group A patients.
AB  - The gene responsible for xeroderma pigmentosum (XP) group A has recently been
      cloned and designated XPA gene. Previous studies have shown that most Japanese
      XPA patients have homozygous mutations for the splicing site of intron 3 of the
      XPA gene, which was recognized by restriction endonuclease (RE) AlwNI (AlwNI
      mutation). Other mutations found to date have been the nonsense mutation at codon
      228 in exon 6, recognized by RE HphI (HphI mutation), and at codon 116 in exon 3,
      recognized by RE MseI (MseI mutation). Using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis, we examined the
      point mutations of the XPA gene in 16 XPA patients, their parents, and their four
      asymptomatic siblings. We found that eight patients were homozygous for the AlwNI
      mutation, two were compound heterozygotes for the AlwNI mutation and the HphI
      mutation, one was a compound heterozygote for the AlwNI mutation and the MseI
      mutation, three were compound heterozygotes for the AlwNI mutation and an
      unidentified mutation, and two were compound heterozygotes for the HphI mutation
      and an unidentified mutation. Investigation of their clinical features suggested
      that the four patients who were heterozygous for the HphI mutation and the AlwNI
      or an unidentified mutation had milder clinical manifestations such as later
      development of skin cancers and milder neurological deterioration, than those
      patients who were either homozygous for the AlwNI mutation or heterozygous for
      the AlwNI mutation and MseI mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577589
TI  - Atopic retinal detachment. Report of four cases and a review of the literature.
AB  - Ocular complications of atopic dermatitis include cataract, blepharitis,
      keratoconjunctivitis, keratoconus, iritis and retinal detachment. The aim of this
      study was to evaluate the characteristics of retinal detachment in atopic
      dermatitis patients. We examined four patients with atopic dermatitis and retinal
      detachment, and performed an extensive review of the literature. There have been
      about 130 reported cases of retinal detachment in patients with atopic dermatitis
      from Japan, in comparison with only a few reports from Europe and the U.S.A. An
      extensive review of the literature revealed that retinal detachment occurs at a
      young age in atopic dermatitis patients, and that often both eyes are involved.
      As retinal detachment is not a rare complication of atopic dermatitis, we propose
      that this type of retinal detachment is designated 'atopic retinal detachment'.
      Dermatologists should be aware of this potential complication of atopic
      dermatitis.

PMID- 7577590
TI  - Fluticasone propionate 0.05% cream in the treatment of atopic eczema: a
      multicentre study comparing once-daily treatment and once-daily vehicle cream
      application versus twice-daily treatment.
AB  - The aim of this study was to compare the efficacy and safety of once-daily with
      twice-daily application of a 0.05% cream formulation of fluticasone propionate in
      the treatment of atopic eczema in adults and children. Two hundred and seventy
      patients with moderate to severe atopic eczema were enrolled in the study, and
      randomized to receive either once-daily or twice-daily fluticasone propionate
      0.05% cream for 4 weeks. Patients randomized to the once-daily group also
      received the vehicle cream to ensure that the study remained blinded. The
      clinical response of a preselected target area of affected skin was assessed by
      investigators at weekly intervals and compared with the baseline. Analysis of the
      investigators' overall assessment of the response of the target area for both the
      'intent-to-treat' population and the per protocol population showed that 79-85%
      of patients were judged a clinical success. For both populations, there was no
      statistically significant difference between the response to once-daily and twice
      daily active treatment (intent-to-treat; P = 0.35; 95% confidence interval for
      difference -14.2 to +5.0 percentage points: per protocol; P = 0.42; 95%
      confidence interval for difference -14.7 to +6.2 percentage points.) The
      improvement in the signs and symptoms was judged a success in 95-97% of patients.
      There was an equal reduction in severity scores for disease activity in both
      groups, and the speed of symptom relief was similar.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577591
TI  - Solitary giant xanthogranuloma and benign cephalic histiocytosis--variants of
      juvenile xanthogranuloma.
AB  - Sequential biopsies taken from a patient with a solitary giant xanthogranuloma,
      an exaggerated macronodular (> 5 cm in diameter) variant of juvenile
      xanthogranuloma, and from a patient with benign cephalic histiocytosis, revealed
      a characteristic time sequence of histopathological findings. Early stages of the
      diseases showed a monomorphous infiltrate of mononuclear vacuolated histiocytes
      positive for KiM1p, HAM56 and factor XIIIa and were characterized by clusters of
      comma-shaped bodies. This was followed by a polymorphous mixture of various
      mononuclear and multinucleate histiocytes additionally labelling with KP1 (CD68)
      and, in occasional cells, for the adherence of peanut agglutinin. A variety of
      ultrastructural changes were found, including dense and regularly laminated
      bodies or lipid droplets. Our findings indicate that both entities are variants
      of a xanthogranulomatous reaction.

PMID- 7577593
TI  - Cutaneous metastatic angiosarcoma with a lethal outcome, following radiotherapy
      for a cervical carcinoma.
AB  - A cutaneous metastatic angiosarcoma was diagnosed in a 79-year-old woman 19 years
      after radiotherapy for a carcinoma of the uterine cervix. The diagnosis was
      confirmed by immunohistochemical staining (factor VIII-related antigen and BMA
      120) and electron microscopic examination. Surgical treatment of the large
      tumour, which was situated in the gluteal region, was not feasible, but electron
      beam therapy resulted in complete remission. However, a further metastasis
      occurred in the inguinal region, and management by total excision, radiotherapy,
      and interferon-alpha treatment was unsuccessful. The patient died 28 months after
      the initial diagnosis of the neoplasm.

PMID- 7577592
TI  - Treatment of severe localized scleroderma by plasmapheresis--report of three
      cases.
AB  - We report three patients with severe, localized scleroderma, and with elevated
      titres of antinuclear antibodies, who were treated by plasmapheresis in
      combination with systemic steroid therapy. The therapeutic effectiveness of
      plasmapheresis was assessed on the basis of improvement in cutaneous and joint
      lesions. In all cases, significant improvement occurred after 2 months of
      therapy. Thus, in addition to treating systemic sclerosis, plasmapheresis can
      also be recommended for treatment of severe cases of localized scleroderma with
      elevated titres of antinuclear antibodies and antibodies to ss-DNA.

PMID- 7577594
TI  - Childhood bullous pemphigoid--report of a case with dermal fluorescence on salt
      split skin.
AB  - Bullous pemphigoid (BP) is an acquired bullous disorder which predominantly
      affects the elderly. It is rare in children, and may be clinically
      indistinguishable from other immunobullous disorders. As routine histology may be
      non-specific, a definitive diagnosis of childhood BP usually depends on the
      results of direct and indirect immunofluorescence investigations. We report a 5
      year-old girl who developed bullous pemphigoid, associated with atypical
      immunofluorescence findings. Indirect immunofluorescence on split-skin showed a
      pure dermal pattern of IgG binding. This is usually suggestive of epidermolysis
      bullosa acquisita, but Western immunoblotting was positive with epidermal
      extracts, confirming a diagnosis of BP. Dermal binding on split-skin occurs in
      about 5% of adult cases of BP, and has not been reported previously in childhood
      BP.

PMID- 7577595
TI  - Spontaneous disappearance of intraepidermal type VII collagen in a patient with
      dystrophic epidermolysis bullosa.
AB  - Recently, a peculiar self-healing neonatal blistering disease has been reported,
      which is characterized by perinuclear stellate inclusions within basilar
      keratinocytes, representing abnormal retention of type VII collagen. We report a
      Japanese patient with this condition, in whom we studied the expression of a
      variety of basement membrane zone (BMZ)-related antigens. Skin biopsy specimens
      at 3 days of age showed abundant accumulation of both the NC-1 domain and the
      collagenous part of type VII collagen within the basal and suprabasal
      keratinocytes, in addition to patchy and weak staining along the BMZ. In
      contrast, at 4 years of age, when the disease activity was markedly attenuated, a
      second biopsy showed complete linear staining of type VII collagen along the BMZ,
      with no detectable intracytoplasmic deposits. Expression of other BMZ-related
      antigens, including laminin 5, alpha 6 and beta 4 integrins, bullous pemphigoid
      antigens 1 and 2, and type IV collagen, was normal in both the biopsy specimens.
      Our observations further confirm that the perinuclear stellate bodies seen in
      this peculiar condition are composed of both collagenous and non-collagenous
      domains of type VII collagen retained within the epidermis, and that these bodies
      disappear when the disease activity remits.

PMID- 7577596
TI  - Protracted cutaneous disorders in association with low CD4+ lymphocyte counts.
AB  - We report two patients with skin disorders usually associated with severe
      immunosuppression, who had low CD4+ lymphocyte counts but normal immunoglobulin
      levels. The patients were HIV negative, and had CD4+ lymphocyte counts just above
      300/mm3, but they presented with cutaneous manifestations of profound
      immunodeficiency. Idiopathic CD4+ lymphocyte deficiency is a recently described
      syndrome which may present with dermatological disease. We discuss the symptom
      complex of our patients in relationship to the diagnosis of idiopathic CD4+
      lymphocyte deficiency.

PMID- 7577597
TI  - Recall phenomenon with the unusual presence of eccrine squamous
      syringometaplasia.
AB  - The recall phenomenon is an inflammatory reaction limited to a previously X
      irradiated field when the patient is treated months or years later with certain
      drugs. Only a few cases have been reported in dermatological journals. We report
      a patient with lymphoma who was treated with low-dose abdominal irradiation and
      high-dose irradiation to the knees and who, 2 months later, when chemotherapy was
      started, developed a pronounced inflammatory reaction limited to the areas
      treated with high-dose irradiation. A skin biopsy specimen showed features of
      radiation damage, marked epidermal changes and extensive eccrine squamous
      syringometaplasia. This case of the recall phenomenon is of interest because we
      have found that there is apparently a radiation dose threshold for this event,
      and because this is the first report of its association with eccrine squamous
      syringometaplasia.

PMID- 7577598
TI  - Systemic corticosteroids are important in the treatment of Fournier's gangrene: a
      case report.
AB  - Fournier's gangrene represents an acute severe necrotizing inflammatory process
      affecting the scrotum and penis. It has an associated mortality of 30-50%. In
      most cases, aetiological factors can be identified, such as diabetes mellitus,
      chronic alcoholism and perianal, perirectal or periurethral infection. The
      disease is characterized by a polybacterial infection, and the classic treatment
      includes surgical removal of the necrotic tissue and the use of broad-spectrum
      antibiotics. We report a case of Fournier's gangrene, histologically
      characterized by a necrotizing vasculitis, in which surgical resection of the
      necrotic tissue and antibiotic treatment failed to halt progression of the
      disease, whereas complete remission was achieved by high-dose corticosteroid
      therapy. This suggests that Fournier's gangrene is related to some form of
      localized vasculitis, and represents a local Shwartzman phenomenon.

PMID- 7577600
TI  - Palmoplantar keratoderma with an unusual composition of stratum corneum and serum
      sterol derivatives: a new entity?
AB  - Little is known about the aetiology and pathogenesis of the different types of
      inherited and acquired palmoplantar keratodermas. We describe a condition of
      painful palmoplantar keratoderma with an altered stratum corneum lipid pattern
      which may be responsible for the excessive cornification. Plantar stratum corneum
      lipids were analysed by quantitative thin-layer chromatography. Serum lipids, and
      the activities and gene loci of the enzymes serum steroid sulphatase and
      arylsulphatase C were also determined. Examination revealed that both the stratum
      corneum and the serum cholesterol sulphate (CS) content were significantly
      elevated in comparison with the stratum corneum cholesterol ester content. The
      cholesterol content was unchanged compared with controls. Serum activities of
      steroid sulphatase and arylsulphatase C were decreased, but not to the extent
      found in recessive X-linked ichthyosis. Their gene loci did not show any
      deletions. This unique distribution of stratum corneum sterol derivatives,
      reflected by the elevated serum CS concentration, may contribute to the altered
      structural and functional properties of intercellular lipid lamellae within the
      stratum corneum of this type of keratoderma.

PMID- 7577599
TI  - Keratoderma, hypotrichosis and leukonychia totalis: a new syndrome?
AB  - We report three members of a family with congenital hypotrichosis, characterized
      by trichorrhexis nodosa and trichoptilosis, dry skin, keratosis pilaris and
      leukonychia totalis. They also developed a progressive transgrediens type of
      palmoplantar keratoderma, and hyperkeratotic lesions on the knees, elbows and
      perianal region. As far as we are aware, this combination of clinical features
      has not been described previously.

PMID- 7577601
TI  - Multiple superficial basal cell carcinomas (basalomatosis) following cobalt
      irradiation.
AB  - Basalomatosis is an uncommon skin condition characterized by the occurrence of
      multiple basal cell carcinomas. Many cases reported in the literature have been
      attributed to arsenic treatment in psoriasis patients. We report a patient with
      basalomatosis caused by cobalt-60 (60Co) irradiation. A 55-year-old farmer
      developed 43 basal cell carcinomas 20 years after treatment of an immunoblastoma
      with 60Co irradiation. All the tumours were located within the radiation fields.
      Other possible causes of basalomatosis, such as arsenic intoxication and basal
      cell naevus syndrome, were excluded. The patient's multiple superficial basal
      cell carcinomas probably represent a late adverse effect of the 60Co irradiation.

PMID- 7577602
TI  - Salivary gland swelling following naproxen therapy.
AB  - We report allergic sialadenitis as a novel side-effect of naproxen, a non
      steroidal anti-inflammatory drug (NSAID). Bilateral swelling of the major
      salivary glands and a rash occurred a few days after the patient had taken the
      drug. High-dose systemic corticosteroid therapy was required to control the
      disorder. Because the salivary gland swelling was not initially recognized as an
      adverse drug reaction, further doses of naproxen were given on two occasions,
      with similar results.

PMID- 7577604
TI  - Narrowband (TL-01) UVB air-conditioned phototherapy for atopic eczema in
      children.

PMID- 7577603
TI  - Primary cutaneous cryptococcosis in an immunocompromized pigeon keeper.

PMID- 7577605
TI  - Methotrexate for the treatment of discoid lupus erythematosus.

PMID- 7577606
TI  - Transglutaminase-positive cells in psoriatic epidermis during treatment with
      calcitriol (1alpha,25 dihydroxy vitamin D3) and tacalcitol (1alpha,24 dihydroxy
      vitamin D3)

PMID- 7577607
TI  - Treatment of recurrent aphthous stomatitis with pentoxifylline.

PMID- 7577608
TI  - Effects of chronic sunlight exposure on the immunological function of the human
      epidermis.

PMID- 7577609
TI  - Basal cell carcinoma associated with a giant comedone.

PMID- 7577610
TI  - Alopecia universalis in liver transplant patients treated with cyclosporin.

PMID- 7577611
TI  - Multiple subepidermal calcified nodules on the eyelids.

PMID- 7577612
TI  - Laser therapy of lichenoid red tattoo reaction.

PMID- 7577613
TI  - Lichen planus and hepatitis C virus (HCV)-related chronic hepatitis: evaluation
      of HCV genotypes.

PMID- 7577614
TI  - Bcl6/Laz3 rearrangements in post-transplant lymphoproliferative disorders.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are well-known complications
      of iatrogenic immune deficiency and are thought to result from the proliferation
      of B cells infected by the Epstein-Barr virus (EBV). Some large cell lymphomas
      occurring in the general population carry a rearrangement of the Bcl6/Laz3 zinc
      finger-encoding gene. 15 EBV-associated PTLD were tested for the presence of
      Bcl6/Laz3 rearrangements by Southern blot analysis using two specific probes
      (F370, F372). One out of 15 cases displayed a rearranged band independent of the
      germline one. In contrast, 10 lymphoblastoid cell lines and one lymphoblastoid
      cell line passaged in an SCID mouse carried only germline alleles of Bcl6/Laz3
      after Southern blot hybridization. This indicates that genetic abnormalities may
      also play an important role in the development of some PTLD.

PMID- 7577615
TI  - Detection of CBFB/MYH11 transcripts in patients with inversion and other
      abnormalities of chromosome 16 at presentation and remission.
AB  - The pericentric inversion of chromosome 16 [inv(16)(p13q22)] and
      t(16;16)(p13;q22) are chromosomal rearrangements frequently associated with AML
      FAB type M4Eo resulting in the production of a fusion gene CBFB/MYH11. We studied
      17 patients with a chromosome 16 abnormality (eight M4Eo, two M1, one M2, three
      M4 without abnormal eosinophils, three MDS) for the presence of CBFB/MYH11
      transcripts using an RT-PCR technique. 10 AML patients with inv(16) tested RT-PCR
      positive (eight at presentation, one in remission, one in remission and relapse).
      Three of these patients were originally reported by cytogenetic analysis to have
      del(16q22) but the positive RT-PCR results prompted a cytogenetic re-examination,
      resulting in the correction of the reports to inv(16). We show that although
      inv(16) is closely associated with AML M4Eo, it can also be detected in cases of
      AML M4 without abnormal eosinophils. Three cases of MDS with inv(16) were also RT
      PCR positive. Four patients with other chromosome 16 abnormalities were RT-PCR
      negative. Four AML patients with inv(16) were studied in remission. All were RT
      PCR positive, including one patient in remission for 108 months and one 22 months
      post allogeneic bone marrow transplant. In the latter two remission patients, RT
      PCR evaluation was positive in bone marrow (BM) but not in peripheral blood,
      suggesting that BM may be the more informative. We conclude that this technique
      is valuable in the accurate molecular classification of AML, particularly as
      treatment options may be influenced by such information. Though RT-PCR is highly
      sensitive in detecting CBFB/MYH11 fusion transcripts during remission, monitoring
      of minimal residual disease in patients with inv(16) remains to be established.

PMID- 7577616
TI  - Patient accrual and quality of participation in a multicentre study on myeloma: a
      comparison between major and minor participating centres.
AB  - The participation of minor centres in randomized trials has been questioned
      because of inferior quality of participation. We have studied this issue in a
      multicentre trial on myeloma, in which 574 patients were included from 99
      participating centres in Sweden, Norway and Denmark from 1 June 1990 until 4
      November 1992. Two hundred and eight patients were entered from university
      hospitals (n = 13), 172 from major county hospitals (n = 25), defined by a
      population base of > or = 100,000 inhabitants, and 194 from minor county
      hospitals (n = 61) with a population base of < 100,000 inhabitants. The accrual
      rate was similar for the three hospital categories, averaging 54% of all reported
      cases, corresponding to 38% of the expected number of newly diagnosed cases. The
      adherence to the study protocol from an administrative point of view was judged
      by the completeness of follow-up forms and the delay in the notification of
      deaths, and from a clinical point of view by the dose intensity for the principal
      drugs of the study, melphalan and interferon. For all studied measures of
      quality, the values were similar for the three hospital categories. We conclude
      that with due informative and educational support, minor centres can make a
      considerable contribution to the patient material of a large randomized trial
      without impairing the quality of the study.

PMID- 7577617
TI  - Clinical significance of elevated soluble interleukin-6 receptor levels in the
      sera of patients with plasma cell dyscrasias.
AB  - We investigated the clinical significance of the serum soluble interleukin-6
      receptor (sIL-6R) in 42 patients with plasma cell dyscrasias (27 with multiple
      myeloma (MM), 13 with monoclonal gammopathy of undetermined significance (MGUS),
      and two with plasma cell leukaemia (PCL)). Serum levels of sIL-6R in normal
      individuals were 77 +/- 21 ng/ml (mean +/- SD, n = 18); those in patients with
      MGUS and with MM were elevated (102 +/- 33 ng/ml, mean +/- SD, P < 0.05 and 126
      +/- 60 ng/ml, mean +/- SD, P < 0.01, respectively). Significant correlations were
      not found between the serum levels of sIL-6R and known prognostic factors (C
      reactive protein, haemoglobin levels, calcium, creatinine, beta 2-microglobulin,
      amounts of M-protein, or percentages of plasma cells in bone marrow). Elevated
      serum sIL-6R did not affect the survival of the patients with MM. Serial
      measurements of sIL-6R together with the clinical course of patients with plasma
      cell neoplasias revealed a good correlation between the sIL-6R level and disease
      activity. We conclude that sIL-6R can be used as a clinical factor correlated
      with the disease activity, at least in some patients with plasma cell neoplasias.

PMID- 7577618
TI  - Malignant transformation of monoclonal gammopathy of undetermined significance
      among out-patients of a community hospital in southeastern Netherlands.
AB  - Patients with a monoclonal gammopathy without evidence of lymphoproliferative or
      plasma cell malignancy within a year are still at risk for malignant
      transformation to multiple myeloma, Waldenstrom's macroglobulinaemia or non
      Hodgkin's lymphoma. In a prospective study performed at the Mayo Clinic, the
      cumulative incidence of malignant transformation was 29% in 14 years. We
      conducted a retrospective study to determine the frequency of malignant
      transformation among 334 unselected out-patients with monoclonal gammopathy of
      undetermined significance (MGUS) from a community hospital in Southeastern
      Netherlands. The cumulative incidence of malignant transformation was 11% in 14
      years (95% confidence interval 6-17%). The long-term survival of patients with
      MGUS was slightly lower than that of the average regional population. In a nested
      case-control study, presence of a kappa light chain was found to be a risk factor
      for malignant transformation (70% of patients who developed malignant
      transformation compared to 30% of the control group, P < 0.01). Likewise, an
      initial high gamma globulin level was also found to be a risk factor (18.7 g/l v
      13.7 g/l in the control group, P < 0.01). As neither risk factor has been
      described before, the significance of these factors for definition of a high-risk
      group among patients with monoclonal gammopathy remains to be determined.

PMID- 7577619
TI  - Variable numbers of BCR-ABL transcripts persist in CML patients who achieve
      complete cytogenetic remission with interferon-alpha.
AB  - A substantial minority of patients with chronic myeloid leukaemia (CML) achieve a
      complete response to treatment with interferon-alpha (IFN-alpha), defined as the
      disappearance of Philadelphia chromosome positive metaphases or, for patients who
      are Philadelphia chromosome negative but BCR-ABL positive, the disappearance of
      the leukaemic clone as assayed by Southern blot. We have measured the levels of
      BCR-ABL transcripts in 20 such patients by quantitative PCR. Results were
      standardized for both quality and quantity of cDNA by quantification of ABL as an
      internal control. All 20 patients had evidence of residual disease; the median
      number of transcripts was 750/micrograms RNA (range 10-22,000) and the median BCR
      ABL/ABL ratio was 0.17% (range 0.0008-3.6%). Our findings show that CML has not
      been eradicated in any patient and that the quantity of residual disease in
      complete responders may vary by as much as four orders of magnitude.

PMID- 7577620
TI  - Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell
      harvests from patients with t(8;21) acute myelogenous leukaemia.
AB  - Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic
      reconstitution after marrow-ablative chemotherapy in patients with acute
      leukaemia because of the possibility that there is a lower risk of leukaemic
      contamination. We have developed a titration assay using a competitive reverse
      transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the
      number of AML1/ETO transcripts so that minimal residual disease (MRD) can be
      monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia
      (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected
      in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained
      from 15 patients with t(8;21) AML. With our competitive RT-PCR assay, the number
      of AML1/ETO transcripts was found to be lower in the second PBSC harvest than
      that in the first in every individual. Furthermore, MRD in PBSC harvests was less
      than that in the corresponding bone marrow obtained on the day of PBSC collection
      in the individual patients studied. In 10 patients who received autologous blood
      stem cell transplantation (ABSCT), we could not find a relationship between the
      number of AML1/ETO transcripts in the infused PBSC harvests and the clinical
      outcome after ABSCT. The present study clearly indicates that although PBSC
      harvests collected after consolidation chemotherapy are contaminated by leukaemic
      cells, the degree of leukaemic contamination may decrease as chemotherapy is
      repeated. The mobilization of PBSC by repeated chemotherapy may provide an
      advantageous source of haemopoietic stem cells for ABSCT.

PMID- 7577622
TI  - Erythroid development of the FDCP-Mix A4 multipotent cell line is governed by the
      relative concentrations of erythropoietin and interleukin 3.
AB  - Conditions are described which promote the erythroid development of the FDCP-Mix
      A4 (A4) cell line with accompanying proliferation of the cells. The requirements
      for this development are low concentrations of interleukin 3 (IL-3) plus the
      presence of erythropoietin (epo) and haemin. When high concentrations of IL-3 are
      added with erythropoietin and haemin the cells do not differentiate and maintain
      their blast cell morphology. Addition of haemin, in the absence of
      erythropoietin, does not promote erythroid development, but the presence of
      haemin with erythropoietin promotes increased proliferation and maturation. The
      morphological maturation of A4 cells along the erythroid lineage is accompanied
      by a gradual loss of clonogenic potential, loss of A4 cell multipotency,
      increased erythropoietin receptor expression, and an increased expression of the
      beta-globin gene. An initial increase in mitogenic responsiveness to
      erythropoietin is followed by a decrease as the cells become refractory to all
      mitogenic stimuli with the acquisition of a postmitotic, mature erythroid cell
      phenotype.

PMID- 7577621
TI  - Structural integrity of the cyclin-dependent kinase inhibitor genes, p15, p16 and
      p18 in myeloid leukaemias.
AB  - The cyclin-dependent kinase inhibitors known as p15, p16 and p18 have been
      suggested as candidates for tumour suppressor genes. We examined these genes for
      their alterations in 46 myeloid leukaemias and 15 myeloid leukaemia cell lines.
      p16 mRNA expression was studied in 41 myeloid leukaemias. The p15 and p16 genes
      were either deleted or mutated in myeloid leukaemia lines at a high frequency
      [6/15 (40%) for p15; 8/15 (53%) for p16] but alterations in primary myeloid
      leukaemias are much less frequent [2/46 (4%) for p15; 3/46 (6%) for p16].
      Alterations of p18 were not found in any of the samples. 13 primary myeloid
      leukaemia samples had negligible levels of p16 mRNA. In summary, the deletions of
      p15 and p16 genes identified in the myeloid leukaemia cell lines probably
      occurred during their in vitro immortalization. Alterations of the p16 or p15
      gene only occurred in primary acute myeloid leukaemia samples that were of mixed
      myeloid/lymphoid lineage (CD19/CD20-positive acute myeloid leukaemia [AML],
      CD2/CD19-positive AML, and lymphoid blastic crisis of chronic myeloid leukaemia).
      Further studies are required to determine if the absence of mRNA expression
      results from inactivation of the p16 gene.

PMID- 7577623
TI  - Kostmann's disease, recombinant HuG-CSF, monosomy 7 and MDS/AML.
AB  - Monosomy 7 (Mo7) and leukaemia predisposition are associated with Kostmann's
      disease (KD). The recent introduction of long-term recombinant HuG-CSF treatment
      in patients with KD, whilst showing significant reductions in infectious
      complications and improved quality of life, might also be associated with an
      increased risk of developing karyotypic abnormalities, myelodysplasia (MDS) and
      acute myeloid leukaemia (AML). We describe a case of an identical twin with
      probable autosomal dominant KD who developed anaemia, Mo7/MDS and AML at 18, 30
      and 50 months respectively from starting r-metHuG-CSF (filgrastim) treatment.
      Further patient analyses are required to establish the natural history of KD and
      to determine what role, if any, filgrastim plays in altering the pathobiology of
      this disorder.

PMID- 7577624
TI  - Hairy cell leukaemia, occupation, and smoking.
AB  - The roles of farm practices, occupational exposures to organic solvents, and
      ionizing radiation in the risk of hairy cell leukaemia (HCL) were examined in a
      French hospital-based multicentre case-control study including 291 cases (229 men
      and 62 women) and 541 controls (425 men and 116 women). No positive association
      was observed with occupations involving exposure to organic solvents or with self
      declared exposures to solvents, but a significant association with self-reported
      exposure to petrol or diesel was found for men (OR = 1.5 CI95% [1.0-2.1]). No
      association with ionizing radiation was detected. Agriculture employment gave an
      odds ratio of 1.7 (CI95% [1.1-2.4]) for men and 2.7 (CI95% [1.1-6.7]) for women.
      Among men, the association seems to affect farmers rather than agricultural
      workers. Self-declared exposure to pesticides or bovine cattle breeding was
      related to HCL risk in both genders. Finally, a significant negative association
      with smoking was observed in men, with an inverse exposure-risk relationship odds
      ratios of 0.6, 0.5 and 0.2, respectively, for cumulative consumptions of < 10, 10
      23 and > or = 24 pack-years), contrasting with an odds ratios clearly > 1 in
      women.

PMID- 7577625
TI  - Large-cell anaplastic non-Hodgkin's lymphoma originating in donor cells after
      allogenic bone marrow transplantation.
AB  - Second neoplasms after allogenic bone marrow transplantation (BMT) occur in donor
      cells; however, host origin generally cannot be excluded. Using fluorescence in
      situ hybridization (FISH) the origin of the malignant population can be proven
      indisputably. In a female patient with CD30+ large-cell anaplastic non-Hodgkin's
      lymphoma (LCAL) after BMT with an HLA-identical brother donor, FISH using anti
      CD30 immunocytochemistry in combination with anti-Y- and anti-EBV RNA probes was
      applied. In pathological lymph nodes the majority of cells were of donor type
      (Y). CD30-positive cells were Y-positive; these cells were also EBV-positive.
      Using FISH and immunocytochemistry we have demonstrated convincingly that this,
      possibly EBV-induced, LCAC originated in donor cells.

PMID- 7577626
TI  - A solitary plasmacytoma of donor origin arising 14 years after kidney
      allotransplantation.
AB  - Allotransplantation of solid organs transfers passenger leucocytes which may give
      rise to a state of persistent microchimaerism. In this report we describe the
      case of a patient who developed a solitary plasmacytoma in a transplanted kidney
      more than 10 years after allografting. The diagnosis was established on the basis
      of the presence of a monoclonal IgG kappa peak in the serum, and light chain
      proteinuria, the plasmacytoid features of tumour cells including cell surface
      expression of IgG, kappa light chains, CD20, CD38 and CD56, the absence of lytic
      bone lesions and a normal bone marrow biopsy, and the disappearance of the
      monoclonal IgG peak after graft nephrectomy. A donor origin of the tumour was
      established by HLA DNA typing of tumour, tumour-free kidney tissue, and
      peripheral blood leucocytes, respectively.

PMID- 7577627
TI  - Expression of interleukin-5 receptors on acute myeloid leukaemia cells:
      association with immunophenotype and karyotype.
AB  - Eosinophilia sometimes occurs in acute myeloid leukaemia (AML) and several
      laboratories have reported that cells with the t(8;21) or structural
      abnormalities of chromosome 16 can proliferate and differentiate to eosinophils
      in the presence of IL-5 in vitro. However, cases without these chromosomal
      abnormalities can also have eosinophilia. We investigated the association between
      the expression of IL-5 receptor (IL-5R) gene, karyotype and phenotype in 35
      patients with AML. All cases expressed the IL-3R but the IL-5R gene was expressed
      predominantly in leukaemic cells with either t(8;21) or CD4-positive
      immunophenotype and was associated with the presence of eosinophilia.

PMID- 7577628
TI  - Heparin-induced thrombocytopenia: an improved method of detection based on lumi
      aggregometry.
AB  - Heparin-induced thrombocytopenia (HIT) is a recognized complication of heparin
      administration. Early detection of this syndrome is essential in the prevention
      of immune-mediated thromboembolic sequelae. The 14C-serotonin release assay (SRA)
      has been used in reference laboratories to identify sera from patients on heparin
      therapy capable of inducing platelet dense granule release. In an attempt to
      improve existing methodologies, we employed luminographic detection of platelet
      dense granule ATP release as an endpoint of HIT antibody-mediated platelet
      activation. Sera tested included 10 SRA confirmed positive and five SRA confirmed
      negative samples (to establish the assay), five samples from patients with
      thrombocytopenia not on heparin therapy and 34 patients suspected of HIT
      syndrome. All SRA confirmed positive sera (n = 19) were positive by the
      luminographic procedure. 24/26 SRA confirmed negative sera and five sera from
      thrombocytopenic patients not on heparin therapy were negative using
      luminography. Two of four sera yielding equivocal SRA results were found to be
      positive by the luminographic technique. The data suggest that the use of a
      lumiaggregometer in the coagulation laboratory to detect HIT antibody-induced
      platelet activation is a reliable alternative to the SRA. The luminographic
      procedure is both rapid and sensitive, and does not require the use of
      biohazardous radio-isotopes.

PMID- 7577629
TI  - Reactivity of autoantibodies from chronic ITP patients with recombinant
      glycoprotein IIIa peptides.
AB  - Chronic immune thrombocytopenia is an autoimmune disorder characterized by
      destructive thrombocytopenia due to the formation of autoantibodies against
      platelet-associated antigens. Most antiplatelet autoantibodies react with either
      the platelet glycoprotein IIb/IIIa or Ib/IX complex, whereas some plasma
      autoantibodies react with glycoprotein IIIa. Previous studies from our laboratory
      suggested that most platelet-associated autoantibodies to platelet GPIIb/IIIa,
      which bind to the intact complex, bind much less avidly to the EDTA-dissociated
      complex, suggesting that the epitopes were complex-dependent. To evaluate this
      further we have studied the binding of platelet-associated autoantibody and
      plasma auto- and alloantibody eluates to large recombinant GPIIIa peptides:
      peptide 1 (GPIIIa Gly1-Val200); peptide 2 (GPIIIa Arg150-Glu400); peptide 3
      (GPIIIa Lys350-Asp550); peptide 4 (GPIIIa Asn450-Val700) and peptide 5 (GPIIIa
      Trp715-Thr762, cytoplasmic fragment). Of the 33 platelet-associated antibody
      eluates tested, all bound avidly to the GPIIb/IIIa complex, but only one showed
      significant binding (>3 SD above control values) to one of the immobilized
      peptides (peptide 3). Conversely, antibodies known to bind to specific regions of
      GPIIIa (murine monoclonal antibody, anti-LIBS2; plasma autoantibody against the
      GPIIIa cytoplasmic fragment and anti-P1A1 antibody) all bound avidly to the
      GPIIIa peptide containing the appropriate epitope. Based on these and our
      previous results, we conclude that platelet-associated antibodies from chronic
      ITP patients rarely bind to epitopes localized to GPIIIa alone.

PMID- 7577630
TI  - Megakaryopoiesis in patients with cyclic thrombocytopenia.
AB  - Megakaryopoiesis was examined in 10 patients (eight females and two males) with
      cyclic thrombocytopenia (CT) to investigate the underlying pathogenesis. Numbers
      of CFU-Meg and megakaryocytes and the mean cytoplasmic area (mean area) of
      megakaryocytes at the peak, nadir, ascent mid phase, and descent mid phase of the
      platelet cycle were determined. The patients were classified as female cases
      group I (cases 1-4; previously diagnosed as ITP and CT occurred during
      remission), female cases group II (cases 5-8; persistent CT from initial
      diagnosis), and male CT (cases 9 and 10). In three of the four female cases in
      group I, numbers of CFU-Meg and megakaryocytes were normal or increased
      persistently during the platelet cycle, whereas the mean area fluctuated in
      synchrony with the platelet cycle, suggesting failure of cyclic production rather
      than platelet destruction. In the female cases in group II and one female case in
      group I, numbers of CFU-Meg and megakaryocytes were also normal or increased at
      four phases of the cycle, but the mean area did not fluctuate, remaining large
      during the cycle, suggesting cyclic destruction or platelet clearance. In
      contrast, in the male patients values for numbers of CFU-Meg, megakaryocytes and
      mean cytoplasmic area fluctuated during the platelet cycle, indicating that
      cyclic changes in megakaryopoiesis generated the platelet cycle. These findings
      indicate that the measurement of cytoplasmic area is useful for distinguishing
      cyclic platelet production from cyclic destruction or clearance in CT.

PMID- 7577631
TI  - Association of changes in monocyte antigen presentation and cytokine production
      in haemophilic boys with treatment and blood-borne virus infection.
AB  - Aspects of monocyte function (antigen presentation and cytokine production (e.g.
      IL-1, IL-6) have been studied in a normal control population and three groups of
      haemophilic boys: group 1 HIV and HCV seronegative and treated only with a single
      heat-treated factor VIII (FVIII) concentrate; group 2 HIV seronegative but HCV
      seropositive; group 3 all HIV and HCV seropositive. Groups 2 and 3 have been
      previously treated with unheated and heated FVIII concentrate. Group 1 boys
      (HIV/HCV uninfected) showed no significant reduction in monocyte antigen
      presentation function nor IL-1 or IL-6 production when compared with a control
      population. Group 2 boys (HCV infected) showed a reduced monocyte antigen
      presentation activity (P < 0.05), but no significant reduction in IL-1 or IL-6
      production. Group 3 boys (HIV and HCV infected) showed a significantly reduced
      monocyte antigen presentation activity (P < 0.001) and an impairment of IL-1 and
      IL-6 production (P < 0.05). A significant reduction of IL-1 and IL-6 production
      was only seen in the HIV and HCV infected haemophilic boys, implicating HIV as an
      aetiological agent. In contrast, reduced monocyte antigen presentation activity
      was seen in haemophilic boys with both HIV and HCV infection or HCV alone. The
      HIV and HCV seronegative boys had normal antigen presentation. The absence of
      immune modulation in haemophilic boys that have not acquired HIV and HCV
      infection suggests that chronic blood-borne virus infections as contributory to
      immune modulation seen in haemophiliacs with virus infections.

PMID- 7577633
TI  - Options for therapy in chronic myeloid leukaemia.

PMID- 7577634
TI  - Use of central venous catheters in children with severe congenital coagulopathy.
AB  - From two U.K. centres 23 children with severe congenital coagulopathy had a total
      of 27 port-a-cath devices inserted to facilitate factor VIII or IX prophylaxis
      (eight patients), domiciliary therapy (seven patients), immunotolerance (four
      patients), or a combination thereof (four patients). Six children had a factor
      VIII inhibitor at the time of insertion. The mean age at operation was 30 months,
      with a range of 9-76 months. The cumulative length of follow-up is 639 months
      with a mean of 27.8 months and a range of 5-79 months. Haemostasis was achieved
      peri- and post-operatively with high-purity concentrate in the majority of
      patients without an inhibitor. All those with an inhibitor had porcine factor
      VIII, except one who had recombinant factor VIIa. The post-operative complication
      rate was 27% (6/23): three had a port-site haematoma (one required removal and
      replacement), two had post-operative infection, and one had swelling caused by
      extravasation. To date there have been 13 documented infections in 10/23 patients
      (five with inhibitor): a rate of 0.24 per follow-up year or 0.67 per 1000 patient
      days. Six were caused by Gram-positive and seven by Gram-negative organisms. Six
      infections could not be eradicated by antibiotics and the port-a-cath system had
      to be removed; in three it was replaced by a second port-a-cath. Although there
      are risks involved in the use of port-a-caths in this population, both clinicians
      and parents involved in the care of these children believe that the benefits are
      considerable and the potential hazards are acceptable.

PMID- 7577632
TI  - Evidence for the aetiological role of blood-borne virus infections in causing
      reduced lectin-induced T-cell proliferation in haemophilic boys.
AB  - T-lymphocyte function, as expressed by polyclonal proliferation to lectin
      mitogens phytohaemagglutinin and concanavalin A, has been studied in a normal
      control population and three groups of haemophilic boys: group 1, HIV and HCV
      seronegative and treated only with a single heat-treated factor VIII (FVIII)
      concentrate; group 2, HIV seronegative but HCV seropositive; group 3, all HIV and
      HCV seropositive. Groups 2 and 3 have been previously treated with unheated and
      heated FVIII concentrate. Group 1 boys (HIV/HCV uninfected) showed no significant
      reduction in lymphocyte proliferation when compared with a control population.
      Group 2 and 3 boys showed an impaired response to these mitogens compared to
      group 1 boys and the control group. There was no relationship between FVIII
      concentrate received and proliferative response. The absence of immune modulation
      in haemophilic boys who have not acquired HIV and HCV infection implicates
      chronic blood-borne virus infections as the major contributory factors to
      impaired lymphocyte proliferative responses seen in haemophiliacs treated with
      large-pool concentrates. The presence of virus infections, such as HCV, may
      account for similar lymphocyte function abnormalities observed in previously
      described cohorts.

PMID- 7577636
TI  - In vitro platelet ageing at 22 degrees C is reduced compared to in vivo ageing at
      37 degrees C.
AB  - In these studies, platelet ageing during in vitro at 22 degrees C was compared
      with in vivo ageing using isotope labelling. Paired fresh and 5-d-stored
      platelets had a mean residual life-span (MRL) of 4.8 +/- 0.7 d and 3.2 +/- 0.9 d,
      respectively. After 2.1 +/- 0.4 d in vivo circulation, the MRL of the fresh
      platelets was equivalent to that of the 5-d-stored in vitro platelets. This
      suggests that platelet ageing for 5 d in vitro at 22 degrees C corresponds to 2.1
      d in vivo ageing at 37 degrees C. Thus, the relative ageing at 22 degrees C in
      vitro was (2.1 d/5 d) = 0.42 of that at 37 degrees C in vivo. A similar ageing
      ratio (0.44) was obtained by measurement of the decrease in MRL during storage at
      22 degrees C of platelets stored for 1, 5, 7, 10 and 14 d relative to the
      decrease in MRL of fresh platelets in vivo. ATP turnover rate at 22 degrees C was
      compared to the rate of 37 degrees C by measurement of the rates of platelet
      oxygen consumption and lactate production in vitro. In vitro ATP turnover at 22
      degrees C versus 37 degrees C, was found to be 10.5 +/- 1.0 versus 21.6 +/- 1.4
      mumol/10(12) plts/min, respectively. Thus, the ATP turnover ratio (0.48) at these
      two temperatures suggests that the relative decrease in ageing at 22 degrees C
      compared to 37 degrees C is similar to the relative decrease in metabolic rate at
      this temperature.

PMID- 7577635
TI  - Splenic irradiation for chronic autoimmune thrombocytopenic purpura in patients
      with contra-indications to splenectomy.
AB  - We treated by splenic irradiation eight patients with chronic idiopathic
      thrombocytopenic purpura (ITP, seven cases) or secondary autoimmune
      thrombocytopenic purpura (one case) who had contra-indications to splenectomy. A
      total dose of 15 Gy was delivered to the spleen, with left kidney protection. One
      patient had a good durable response (> 1 year); two patients had a good transient
      response (of 3 months duration) but they responded again to a second course of
      irradiation; two patients had only partial response, but have required no other
      treatments for 2 years; the three remaining patients had no response. Side
      effects were minor. Therefore splenic irradiation appears to be a therapeutic
      option in patients with chronic ITP who have contra-indications to splenectomy.

PMID- 7577637
TI  - Prevention of donor-specific T-cell unresponsiveness after buffy-coat-depleted
      blood transfusion.
AB  - The immunosuppressive effect of blood transfusions has been demonstrated in
      several clinical studies. The effect is probably mediated by HLA-class-II-bearing
      donor leucocytes, because results from laboratory tests show specific down
      regulation of the recipient's T-Cell response after administration of blood from
      donors sharing one HLA haplotype with the recipient. In the present study we
      evaluated the immunosuppressive potential of buffy-coat-depleted red cell
      transfusions in patients waiting for renal transplantation, by measuring the
      frequency of cytotoxic precursor T cells before and after transfusion. The buffy
      coat was removed from whole blood by the Optipress system and resulted in > 97%
      depletion of lymphocytes and monocytes. A single transfusion of HLA-haplotype
      matched buffy-coat-depleted red cells induced donor-specific down-regulation of T
      cell responses in only two of 14 patients. Since HLA-class-II-bearing cells are
      also involved in the induction of anti-HLA antibodies, we evaluated
      retrospectively the incident of HLA alloimmunization after a single transfusion
      of buffy-coat-depleted red cells. No anti-HLA antibodies were found in 140
      patients at risk for primary immunization. We conclude that the poor
      immunological responses found after a single transfusion of HLA-haplotype-matched
      buffy-coat-depleted red cells is due to the small number of residual HLA-class-II
      bearing donor cells. This blood component should not be used for induction of
      immunosuppression.

PMID- 7577638
TI  - Results of long-term deferiprone (L1) therapy: a report by the International
      Study Group on Oral Iron Chelators.
AB  - This report updates the combined experience of four centres involved in the long
      term treatment of transfusional iron overload in 84 patients with the oral iron
      chelator deferiprone (L1) over 167 patient-years. The source of L1 was variable,
      including two university research laboratories and three pharmaceutical firms.
      Compliance was rated as excellent in 48%, intermediate in 36%, and poor in 16% of
      patients. On a mean L1 dose of 73-81 mg/kg/d, urinary iron excretion was stable,
      at around 0.5 mg/kg/d, with no indication of a diminishing response with time.
      Serum ferritin showed a very steady decrease with time from an initial mean +/- 1
      SD of 4207 +/- 3118 to 1779 +/- 1154 micrograms/l after 48 months (P < 0.001). 17
      patients abandoned L1 therapy. Major complications of L1 requiring permanent
      discontinuation of treatment included agranulocytosis (three), severe nausea
      (four), arthritis (two) and persistent liver dysfunction (one). The remaining
      patients abandoned treatment because of low compliance (three) and conditions
      unrelated to L1 toxicity (four). Lesser complications permitting continued L1
      treatment included transient mild neutropenia (four), zinc deficiency (12),
      transient increase in liver enzymes (37), moderate nausea (three) and arthropathy
      (17). There was no treatment-related mortality. Although the complications
      associated with L1 treatment are significant and require close monitoring, they
      do not preclude effective long-term therapy in the vast majority of patients.
      Further well-controlled prospective studies of L1 are required in order to enable
      proper judgement of its suitability for general long-term clinical use.

PMID- 7577639
TI  - Soluble c-kit molecule in serum from healthy individuals and patients with
      haemopoietic disorders.
AB  - The proto-oncogene, c-kit, encodes a transmembrane tyrosine kinase receptor (KIT)
      and plays an important role in haemopoiesis. We have identified a 95 kD soluble
      form of KIT (S-KIT) in culture supernatant of human megakaryoblastic cell line,
      CMK. To study the physiological significance of S-KIT, we have established a
      sensitive sandwich ELISA system. Serum samples from healthy individuals contained
      detectable amounts of S-KIT. Next, we determined a total of 220 samples from 134
      patients with haemopoietic disorders. A considerable number of patients with
      acute myeloid leukaemia (AML), especially those with more immature phenotypes
      (M0, M1 or M2) had elevated levels of serum S-KIT. Those levels decreased to the
      normal range after effective chemotherapy. In chronic myeloid leukaemia, patients
      with myeloid blastic crisis showed markedly elevated levels of serum S-KIT. In
      contrast, S-KIT levels decreased in cases with either acute or chronic lymphoid
      leukaemia. There was a tendency for patients with severe aplastic anaemia to show
      decreased levels, but it was not significant. In myelodysplastic syndrome, S-KIT
      levels appeared to vary by subsets, with higher concentration in more advanced
      forms of the disease. Although the functional role of S-KIT is not yet
      elucidated, these results suggest that the serum S-KIT levels may reflect the
      pathological states of various haematological disorders.

PMID- 7577640
TI  - Interleukin-11 enhances gastrointestinal absorption of iron in rats.
AB  - The effect of parenteral administration of IL-11 on gastrointestinal iron
      absorption was evaluated. A significant increase in the absorption of 59Fe-tagged
      food iron fed to fasting rats was observed when two subcutaneous injections of IL
      11 were given 48 and 24 h prior to testing. Relatively similar increases of 25%
      were observed with IL-11 doses of 300, 600 and 1000 micrograms/kg for each
      injection. The increase in absorption did not appear to be related to changes in
      erythropoiesis. These findings raise the possibility that the enhanced absorption
      of iron which occurs with ineffective erythropoiesis may in part be mediated by
      multifunctional haemopoietic growth factors.

PMID- 7577641
TI  - Interleukin-3 priming in acute myeloid leukaemia patients.
AB  - Several studies have demonstrated that G-CSF, GM-CSF and, in particular, IL-3 can
      effectively recruit acute myeloid leukaemia (AML) blasts into the cell cycle,
      resulting in a significant increase in cytosine-arabinoside (Ara-C) mediated
      cytotoxicity in vitro. Since IL-3 has shown biological and clinical activity, we
      investigated the cell kinetic effects of rIL-3 and high-dose Ara-C/idarubicin in
      three patients with refractory AML selected for the presence of chromosome 7
      monosomy; this enabled differentiation between the effects of IL-3 on leukaemic
      and on normal cells. The in vivo administration of rhIL-3 (250 micrograms/m2d
      s.c. for 6-10d) recruited AML blasts into the cell cycle in two of the three
      patients, and this effect resulted in an increase in in vitro growth of
      clonogenic cells (CFU-L) and of their S-phase fraction. The percentage of
      leukaemic cells with monosomy 7 increased only in the two cases who showed a
      proliferative response. Normal cells were not recruited, even when rhIL-3 was
      administered for up to 10 d. In vitro studies showed an increased Ara-C
      cytotoxicity on clonogenic AML cells, in particular with IL-3 plus GM-CSF, thus
      confirming the priming effects of IL-3 in the two responding cases. The results
      of this study suggest that rhIL-3 can selectively recruit leukaemic cells into
      the cell cycle. Although leukaemic blasts can be sensitized to Ara-C, other
      mechanisms of primary blast resistance may limit the clinical benefit of kinetic
      based approaches.

PMID- 7577642
TI  - Increased expression of Fas antigen on bone marrow CD34+ cells of patients with
      aplastic anaemia.
AB  - Fas antigen, a receptor molecule that mediates signals for programmed cell death,
      is involved in T-cell-mediated killing of malignant, virus-infected or allogeneic
      target cells. Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF
      alpha), potent inhibitors of haemopoiesis, enhance Fas receptor expression on
      bone marrow (BM) CD34+ cells, and both cytokines render haemopoietic progenitor
      cells susceptible to Fas-mediated inhibition of colony formation due to the
      induction of apoptosis. Haemopoietic suppression in aplastic anaemia (AA) has
      been associated with aberrant IFN-gamma, increased TNF-beta expression, and
      elevated numbers of activated cytotoxic T-cells in marrow. We have now examined
      Fas antigen expression in fresh AA BM samples. In normal individuals few CD34+
      cells expressed Fas antigen and normal marrow cells had low sensitivity to Fas
      mediated inhibition of colony formation. In contrast, in early AA, BM CD34+ cells
      showed markedly increased percentages of Fas receptor-expressing CD34+ cells,
      which correlated with increased sensitivity of AA marrow cells to anti-Fas
      antibody-mediated inhibition of colony formation. The proportion of Fas antigen
      bearing cells was lower in recovered patients' BM. Fas antigen was also detected
      in the marrow of some patients with myelodysplasia, especially the hypocellular
      variant. These results are consistent with the hypothesis that AA CD34+ cells,
      probably including haemopoietic progenitor cells, express high levels of Fas
      receptor due to in vivo exposure to IFN-gamma and/or TNF-alpha and are suitable
      targets for T-cell-mediated killing. Our results suggest that the Fas
      receptor/Fas ligand system are involved in the pathophysiology of BM failure.

PMID- 7577644
TI  - Erythropoietin in the myelodysplastic syndromes: meta-analytical study.

PMID- 7577645
TI  - Fatal haemoptysis in filamentous mycosis.

PMID- 7577643
TI  - Persistent lymphocytosis of natural killer cells after splenectomy.

PMID- 7577646
TI  - Instability of a variable number tandem repeat in intron 40 of the human von
      Willebrand factor gene.

PMID- 7577647
TI  - Recombinant erythropoietin for myelodysplastic syndromes.

PMID- 7577648
TI  - Changes in c-Kit expression and effects of SCF during differentiation of human
      erythroid progenitor cells.
AB  - We analysed c-Kit expression during erythroid differentiation using
      immunocytochemical staining and flow cytometric analysis. Burst-forming units
      erythroid (BFU-E)-derived cell aggregates were identified in methylcellulose
      cultures containing human umbilical cord blood CD34+ cells and were stained by
      the indirect immunoalkaline phosphatase method. To investigate the changes in
      levels of cell-surface c-Kit expression, we subjected progenitor cells in liquid
      culture to flow cytometric analysis. In addition, the effects of stem cell factor
      (SCF) on cell-surface c-Kit expression were analysed in these two culture systems
      and the effects of SCF on erythroid colony formation were studied in a
      methylcellulose culture. c-Kit was expressed on the cell surface from BFU-E to
      erythroid precursors recognized morphologically as basophilic erythroblasts. Flow
      cytometric analysis showed that c-Kit expression increased until 6 d in liquid
      culture, and that decreased expression of c-Kit was associated with the increased
      expression of glycophorin A. Moreover, SCF increased the size of erythroid
      colonies when added at days 0, 4 and 8 in methylcellulose cultures. These results
      indicate that the c-Kit/SCF system still plays in proliferation of erythroid
      progenitor cells at the colony-forming units-erythroid stage. Finally, expression
      of c-Kit in erythroid progenitor cells cultured without SCF showed a diffuse
      pattern on the cell surface, whereas we observed positive c-Kit immunoreactivity
      in the region of the Golgi apparatus of these cells cultured with SCF. Flow
      cytometric analysis also showed that the levels of cell-surface c-Kit expression
      decreased in the presence of SCF. These results suggest that SCF induced down
      modulation of cell-surface c-Kit expression, despite continuous synthesis of c
      Kit protein.

PMID- 7577649
TI  - Quantitation of soluble and membrane-bound Fc gamma RIIA (CD32A) mRNA in
      platelets and megakaryoblastic cell line (Meg-01).
AB  - Fc gamma receptors (Fc gamma Rs) are glycoproteins on platelet surface that bind
      IgG-containing immune complexes. However, excessive binding of immune complexes
      leads to platelet activation and thrombosis or increased platelet clearance and
      thrombocytopenia. In this study, Fc gamma R transcripts in platelets and
      megakaryoblastic cell line (Meg-01) were investigated using specifically designed
      oligonucleotides and a new quantitative in situ hybridization assay. Platelets
      and Meg-01 cells were found to express only Fc gamma RII transcripts. Of Fc gamma
      RIIA mRNA isoforms (Fc gamma RIIA, B and C), Fc gamma RIIA mRNA predominates in
      these cells. Platelets and Meg-01 cells contain both alternative spliced forms of
      Fc gamma RIIA mRNA, those with and without the transmembrane (TM) exon and both
      forms were present in near equal amounts. In contrast, Fc gamma RIIA transcript
      with the TM exon predominates in neutrophils and monocytes, suggesting that the
      splicing of the TM exon is under lineage-specific control.

PMID- 7577650
TI  - Severe congenital neutropenia unresponsive to G-CSF.
AB  - Severe congenital neutropenia (SCN) is an inherited disorder characterized by
      severe neutropenia and recurrent infections from an early age, with bone marrow
      showing a maturational arrest of granulopoiesis at the promyelocyte stage. Since
      the introduction of G-CSF therapy the prognosis for affected children has
      improved dramatically. We describe two patients with SCN who were clinically
      unresponsive to G-CSF therapy. The results of in-vitro colony assays from these
      two patients are presented together with the results from the mother of one of
      these patients who also has a chronic neutropenia, and a further child with SCN
      who responded to treatment with G-CSF.

PMID- 7577651
TI  - Degradation of platelet glycoprotein Ib by elastase released from primed
      neutrophils.
AB  - Mutual interactions between neutrophils (PMN) and platelets are recognized to be
      important in modulating the respective functions of these two cell types. Here we
      show that primary granule secretion from appropriately-stimulated PMN can lead to
      complete proteolytic removal of GPIb from the platelet surface. Thus, when the
      PMN in PMN/platelet mixtures were stimulated by FMLP, platelets lost GPIb as
      measured by ristocetin-induced aggregation, flow cytometry and SDS-PAGE analysis.
      This loss was most marked when PMN were primed by GM-CSF, and could be inhibited
      by a specific elastase inhibitor. As expected, the alpha 1-antiproteinase in
      plasma inhibited GPIb loss, but when PMN were strongly stimulated by FMLP and GM
      CSF in the presence of platelets this inhibition was incomplete or absent. It is
      concluded that joint priming of PMN with GM-CSF and platelets can cause a
      previously unrecognized degree of primary granule secretion which, via elastase,
      leads to platelet GPIb loss. We suggest that this loss is likely to be of
      physiological and pathophysiological importance.

PMID- 7577652
TI  - A simple and sensitive method for determining plasma cell isotype and
      monoclonality in bone marrow using flowcytometry.
AB  - In this paper we describe a new, rapid and sensitive method to determine plasma
      cell isotype and clonality in bone marrow using flowcytometry. With the use of a
      new fixation and permeabilization reagent (Permeafix), which preserves cell
      structure and morphology, and a monoclonal antibody (Mab) specific for plasma
      cells (B-B4), it has become possible to specifically select plasma cells and to
      determine the cytoplasmatic immunoglobulins by flowcytometry. Thirty successive
      bone marrow aspirates from multiple myeloma patients and patients with MGUS were
      studied as well as 10 bone marrow samples from patients with reactive
      plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin
      smears and FACS analysis. There were no discrepancies between plasma cell isotype
      as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow
      detection of very low numbers of plasma cells and to determine whether these
      plasma cells are mono- or polyclonal. Possible applications are discussed.

PMID- 7577653
TI  - Molecular defect of a phosphoglycerate kinase variant associated with haemolytic
      anaemia and neurological disorders in a large kindred.
AB  - The X-chromosome-linked phosphoglycerate kinase (PGK) deficiency associated with
      severe chronic and acute haemolytic anaemia and mental disorders was first
      described in a large Chinese kindred in 1969. The molecular abnormality of this
      original variant remained to be identified. The red cell PGK activity was only
      about 5%, but the activity of the patients' lymphoblastoid cells was about 15% of
      normal. The PGK mRNA content of the patients' lymphoblastoid cells were normal.
      Analysis of the patients' mRNA showed the existence of a nucleotide transversion
      A-->T at position 491 (counting from adenine of the initiation codon). The
      mutation should cause an amino acid substitution Asp-->Val at position 163 of the
      enzyme. The replacement of the acidic aspartic acid by a hydrophobic valine is
      expected to induce drastic structural instability resulting in severe enzyme
      deficiency in the patients' tissues. The genotypes of two affected males, their
      mothers and 22 females of the family were identified by the PCR-mediated method
      using their genomic DNA samples. 13/24 females examined were found to be variant
      heterozygous. In this large family, affected males over three generations have
      died at a pre-adult age. Post- and pre-natal genotyping of the family members may
      prevent future problems.

PMID- 7577654
TI  - Molecular genetics of glucose-6-phosphate dehydrogenase (G6PD) deficiency in
      Spain: identification of two new point mutations in the G6PD gene.
AB  - In order to explore the nature of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency in Spain, we have analysed the G6PD gene in 11 unrelated Spanish G6PD
      deficient males and their relatives by using the polymerase chain reaction and
      single-strand conformation polymorphism (PCR-SSCP) analysis combined with a
      direct PCR-sequencing procedure and PCR-restriction enzyme (RE) analysis. We have
      identified eight different missense mutations, six of which have been reported in
      previously described G6PD variants. In nine patients who had presented with acute
      favism we found the following mutations: G6PD A-376G-202A (four cases), G6PD
      Union1360T (two cases), G6PD Mediterranean563T (one case) and G6PD Aures143C (one
      case). In the remaining patient a novel A to G transition was found at nucleotide
      position 209 which has not been reported in any other ethnic group. This mutation
      results in a (70) Tyr to Cys substitution and the resulting G6PD variant was
      biochemically characterized and designated as G6PD Murcia. This new mutation
      creates a Bsp 1286I recognition site which enabled us to rapidly detect it by PCR
      RE analysis. In two patients with chronic non-spherocytic haemolytic anaemia
      (CNSHA) we found the underlying genetic defects, as had been noted previously, to
      be located within a cluster of mutations in exon 10. One of them had the T to C
      transition at nucleotide 1153, causing a (385) Cys to Arg substitution,
      previously described in G6PD Tomah. The other, previously reported as having a
      variant called G6PD Clinic, has a G to A transition at nucleotide 1215 that
      produces a (405) Met to Ile substitution, thus confirming that G6PD Clinic is a
      new class I variant.

PMID- 7577655
TI  - Glucosamine 6-phosphate deaminase in normal human erythrocytes.
AB  - In the course of an investigation of hexosamine catabolism in the human malaria
      parasite, Plasmodium falciparum, it became apparent that a basic understanding of
      the relevant enzymatic reactions in the host erythrocyte is lacking. To acquire
      the necessary basic knowledge, we have determined the activities of several
      enzymes involved in hexosamine metabolism in normal human red blood cells. In the
      present communication we report the results of studies of glucosamine 6-phosphate
      deaminase (GlcN6-P) using a newly developed sensitive radiometric assay. The mean
      specific activity in extracts of fresh erythrocytes assayed within 4h of
      collection was 14.7 nmol/h/mg protein, whereas preparations from older
      erythrocytes that had been stored at 4 degrees C for up to 4 weeks had a mean
      specific activity of 6.2 nmol/h/mg. Characterization of the deaminase by
      chromatofocusing gave a pI of 8.55. The enzyme was optimally active at pH 9.0 and
      had a Km of 41 microM. The metal chelators EDTA and EGTA were non-inhibitory;
      however, inhibition was observed in the presence of metal ions, especially Cu2+,
      Ni2+ and Zn2+. In addition, the deaminase was also inhibited by several sugar
      phosphates including the reaction product, fructose 6-phosphate.

PMID- 7577656
TI  - Interferon-alpha (IFN-alpha) inhibits granulocyte-macrophage colony-stimulating
      factor (GM-CSF) expression at the post-transcriptional level in murine bone
      marrow stromal cells.
AB  - Recently it has been shown that IFN-alpha inhibits expression of GM-CSF in
      adherent cells of human long-term bone marrow cultures (LTBMC) stimulated with
      interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) or endotoxin. The
      murine bone marrow stromal cell line +/+(-1).LDA11 was used to further define
      regulatory mechanisms of IFN-alpha inhibition on GM-CSF expression. This cell
      line originated from a murine Dexter type culture and exhibits a preadipocytic
      phenotype. As in human LTBMC, we could demonstrate a inhibitory effect of IFN
      alpha co-incubation on GM-CSF activity in serum-free supernatants of +/+(
      1).LDA11 stromal cell cultures stimulated with IL-1 or TNF-alpha or the
      combination of IL-1 plus TNF-alpha. IFN-alpha inhibitory effect on GM-CSF
      expression was shown to be dose dependent with minimal response at 10 U/ml and
      maximal inhibition at a dose of 500 U/ml. Northern blot analysis confirmed these
      data at the mRNA level. Reprobing of Northern blots for interleukin-6 (IL-6) mRNA
      showed increased expression after IFN-alpha incubation, demonstrating specific
      and differential regulatory effects of IFN-alpha on cytokine production in bone
      marrow stromal cells. Inhibition of GM-CSF mRNA by IFN-alpha was time dependent,
      starting at about 90-120 min post-treatment. Cycloheximide (CHX) incubation
      abolished the inhibitory effect of IFN-alpha on GM-CSF expression, suggesting the
      requirement of a labile protein. Reporter gene studies were used in order to
      evaluate the effect of IFN-alpha incubation on GM-CSF mRNA transcription in
      stromal cells. For this purpose, GM-CSF promoter fragments were subcloned into a
      luciferase expression vector. Neither constitutive nor TNF-alpha stimulated GM
      CSF transcription was inhibited by IFN-alpha coincubation. On the other hand,
      actinomycin-D chase experiments revealed a reduced GM-CSF mRNA stability after
      IFN-alpha incubation. The induction of a RNAase, possibly a 2-5A-dependent
      RNAase, by IFN-alpha may be a possible cause for the increased GM-CSF mRNA decay.
      These results show a regulatory role for IFN-alpha in the bone marrow
      microenvironment possibly involved in the myelosuppressive effect of IFN-alpha
      therapy or viral infections.

PMID- 7577657
TI  - An association of aplastic anaemia in Thailand with low socioeconomic status.
      Aplastic Anemia Study Group.
AB  - The relationship of socioeconomic status to the risk of aplastic anaemia was
      evaluated in a case-control study conducted in Bangkok and two rural regions of
      Thailand (Khonkaen and Songkla). Among 152 cases and 921 controls there were
      significant trends of increasing risk with decreasing years of education (P =
      0.01) and total household income (P = 0.0001), after control for confounding. The
      relative risk estimate for those with monthly incomes of < 1500 baht (about $60
      U.S.) was 3.9 (95% confidence interval 2.1-7.3) compared to those with monthly
      incomes of at least 5000 baht (about $200). The pattern of increasing risk with
      decreasing income was observed in all three regions, with significant trends in
      Bangkok (P = 0.004) and Khonkaen (P = 0.003). This finding may partly explain the
      high incidence of aplastic anaemia in Thailand. Low socioeconomic status may be a
      surrogate for one or more environmental factors that could cause aplastic
      anaemia, such as infectious pathogens or toxic exposures.

PMID- 7577658
TI  - Beta-thalassaemia unlinked to the beta-globin gene interacts with sickle-cell
      trait in a Portuguese family.
AB  - An autosomally transmitted hypochromic microcytic mild anaemia with elevated
      haemoglobin (Hb) A2 and globin chain imbalance has been observed in a three
      generation family of Portuguese origin. Extensive DNA analysis of the beta-globin
      gene cluster, including the complete sequencing of the beta-globin gene and
      flanking regions, failed to reveal any genetic alteration. The co-segregation of
      sickle-cell trait in this family enabled us to postulate a defective erythroid
      trans-acting factor was playing a role in the down-regulation of both beta A- and
      beta S-globin genes. Among the transcription factors that could possibly have
      caused the reported phenotype, NF-E2 is unlikely to be implicated, whereas Nrf1
      and Nrf2 cannot be ruled out. Thus, this family carries a novel beta-thalassaemia
      autosomal determinant unlinked to the beta-globin gene. This observation
      reinforces the notion of the haemoglobinopathies as single gene disorders under
      polygenic regulation.

PMID- 7577659
TI  - Management of persistent B19 parvovirus infection in AIDS.
AB  - An HIV+ 26-year-old white man with a CD4 count of 0.06 x 10(9)/l was found to
      have red blood cell aplasia secondary to B19 parvovirus infection. Regular
      infusions of intravenous immunoglobulin (IVIG) were begun and resulted in marked
      reticulocytosis and correction of anaemia. The patient has been followed for over
      4 years and has become anaemic and reticulocytopenic whenever IVIG was
      interrupted. Serial dot blot analysis of the patient's sera for B19 parvovirus
      DNA showed absence of DNA immediately following IVIG treatments but reappearance
      within 3-6 weeks. Regular IVIG was effective in controlling but not eradicating
      B19 parvovirus infection in this HIV+ patient.

PMID- 7577660
TI  - Corticosteroid resistance is increased in lymphoblasts from adults compared with
      children: preliminary results of in vitro drug sensitivity study in adults with
      acute lymphoblastic leukaemia.
AB  - The prognosis of acute lymphoblastic leukaemia (ALL) in adults is poor compared
      with children in terms of complete remission (CR) and leukaemia-free survival. In
      children in vitro resistance of leukaemic cells to various cytotoxic agents is an
      independent poor prognostic marker, but the relevance of in vitro drug resistance
      in adults to poor prognosis has not been described. Lymphoblasts from 16 adults
      and 32 children with ALL at initial presentation were assayed for in vitro drug
      sensitivity in a short-term culture system using the reduction of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of
      cell viability. The following drugs were tested: prednisolone, daunorubicin,
      mitozantrone, etoposide, melphalan and 6-thioguanine. At initial presentation,
      lymphoblasts from adults demonstrated a significantly higher degree of in vitro
      resistance to prednisolone than those from children (P < 0.01). Glucocorticoid
      resistance may be a fundamental difference between adult and childhood ALL which
      may underlie different biological aspects and also explain the difference in
      prognosis. Lymphoblasts from adults who achieved CR were more sensitive in vitro
      to prednisolone (P = 0.07), daunorubicin (P < 0.05), mitozantrone (P < 0.01) and
      melphalan (P < 0.05) than cells from those who did not. The MTT assay can predict
      response to induction chemotherapy in adults and therefore discriminate between
      standard- and high-risk patients. The assay, however, is not suitable for
      selection of the most effective agent for treatment because of in vitro cross
      resistance of lymphoblasts to various drugs tested.

PMID- 7577661
TI  - The efficacy of tamoxifen as an antiproliferative agent in vitro for benign and
      malignant pediatric glial tumors.
AB  - Recent studies have suggested that the triphenylethylene antiestrogen tamoxifen
      inhibits the proliferation in vitro of a substantial percentage of cell lines
      derived from adult high-grade gliomas, potentially acting through inhibition of
      the second messenger protein kinase C. These findings have formed the impetus for
      clinical trials of this agent in adults with malignant gliomas. However, it has
      previously remained uncertain whether tamoxifen has a similar inhibitory effect
      on the proliferation of pediatric high-grade gliomas, and whether low-grade
      gliomas, which constitute the majority of glial neoplasms in children, are also
      inhibited by this agent. To address these issues, the present study examined the
      effect of tamoxifen on proliferation and viability in a series of low-passage
      cell lines derived both from low-grade and high-grade pediatric gliomas. This
      agent was tested in three malignant gliomas, two pilocytic astrocytomas, two non
      pilocytic low-grade astrocytomas, 1 mixed glioma, and 1 oligodendroglioma.
      Tamoxifen produced a dose-dependent inhibition of proliferation in two of the
      three malignant glioma cell lines and in each of the low-grade glioma cell lines
      with a 50% effective dose of approximately 3 micrograms/ml (5.4 microM), which is
      comparable to the IC50 for inhibition of PKC activity by this agent. No
      significant cytotoxicity was encountered at this concentration. However, complete
      elimination of proliferation was achieved with a dose of 10 micrograms/ml (17.8
      microM), which produced a direct cytotoxic effect. We conclude that tamoxifen
      inhibits proliferation of cell lines derived from both low-grade and high-grade
      pediatric glial tumors in vitro at concentrations that may be achievable
      clinically with high-dose oral therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577664
TI  - Hypothalamic hamartoma and the Pallister-Hall syndrome.
AB  - The Pallister-Hall syndrome (PHS) was initially described as the congenital
      hypothalamic 'hamartoblastoma' syndrome in 1980. Cardinal manifestations of the
      syndrome consist of a hypothalamic hamartoma and extracranial abnormalities,
      initially thought to be fatal in the perinatal period. The original pathologic
      description of these hypothalamic lesions were from infants who died in the
      perinatal period and revealed small cells of variable density which resembled
      primitive undifferentiated germinal cells and appeared to invade the hypothalamic
      nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been
      removed from older infants and children with this syndrome and reveal a more
      mature histologic appearance typical of a hypothalamic hamartoma. We present 2
      new cases of PHS who underwent surgery and demonstrate the maturational nature of
      the hypothalamic lesion and the phenotypic variability of the syndrome.

PMID- 7577663
TI  - De novo Chiari-I malformation in infants demonstrated by sequential magnetic
      resonance imaging scans. Report of two cases.
AB  - In this report we demonstrate the de novo development of Chiari-I malformation
      with hydrosyringomyelia in 2 toddlers on serial brain magnetic resonance imaging
      scans. We speculate that a mismatch in bony and neural development is the
      underlying mechanism of these de novo Chiari malformations.

PMID- 7577662
TI  - High-activity 125I interstitial irradiation in the treatment of pediatric central
      nervous system tumors: a pilot study.
AB  - Malignant pediatric tumors of the central nervous system (CNS) have a poor
      prognosis, with local failure rates as high as 50%. In an attempt to improve
      local tumor control, we used stereotactic interstitial therapy with 125I implants
      in patients with recurrent/secondary or newly diagnosed CNS malignancies.
      Catheters were placed using computed tomography (CT) guidance; computerized
      dosimetry was completed with the aid of orthogonal films. Implants delivered
      1,000 cGy/day to the tumor periphery (0.5 cm beyond the boundary of enhancement
      on CT scans), to a total dose of 60 Gy. Hyperfractionated external beam
      irradiation (HEBI), started 2-4 weeks after removal of implants, delivered total
      doses of 66-70.4 Gy in 110-cGy fractions twice daily to a 3-cm margin around the
      implant volume. Eight of the 11 patients with newly diagnosed tumors also
      received 48.4 Gy HEBI to the craniospinal axis. Tumor regression was noted at 2
      months after implantation in the 4 patients treated for recurrent/secondary
      tumors; local progression was subsequently documented in 2 cases at 6 and 20
      months after implantation, while a third patient died 6 months after implantation
      with no evidence of local recurrence. The remaining recurrent/secondary tumor
      patient has no evidence of active recurrence 15 months after implantation. Local
      control was maintained in 9 of the 11 patients treated for primary tumors for a
      median of 27 months (range 15 to 48+ months). The two local failures occurred at
      5 and 7 months after implantation. Six patients are alive without evidence of
      progressive disease (median = 23 months after implantation). There were no severe
      acute toxicities, but 7 patients later developed histologically confirmed tumor
      necrosis. Quality of life assessment (QLA) following initial primary therapy with
      implantation was evaluated utilizing an established criteria and found to be
      excellent with only one child showing marked QLA score decrease which was related
      to neurosurgical intervention for radiation-induced necrosis and dysfunctional
      family social situation. This small series suggests that stereotactic 125I
      implantation followed by HEBI merits further evaluation in selected children with
      supratentorial malignant lesions.

PMID- 7577666
TI  - Intraventricular hemorrhage complicating ventricular catheter revision: incidence
      and effect on shunt survival.
AB  - A retrospective study was conducted on 105 pediatric patients who underwent shunt
      revision between 1986 and 1993 at the Alberta Childrens Hospital (Calgary) to
      determine the frequency of intraventricular hemorrhage (IVH) with ventricular
      catheter revision. Ventricular catheter revision was performed 143 times in 74
      patients. Intraventricular hemorrhage was noted intra-operatively or on post
      operative computed tomographic (CT) scans on 45 occasions for an overall
      incidence of 31%. IVH was associated with a significantly shorter time (p <
      0.0002) to subsequent shunt revision (227.33 +/- 392.24 days) compared to
      catheter survival when no hemorrhage was noted (735.02 +/- 1,001.11 days). This
      study raises several important questions about the prevention and management of
      IVH during shunt revision. It also provides the first published report on the
      incidence of IVH during shunt revision, thereby setting a standard to which
      future studies can be compared.

PMID- 7577665
TI  - Complications of fourth-ventricular shunts.
AB  - Fourth-ventricular shunting is commonly used to treat symptomatic posterior fossa
      cysts of the Dandy-Walker malformation and trapped fourth ventricle. Although the
      benefits of this procedure have been widely reported, there is a paucity of data
      on the pitfalls of posterior fossa shunting in the neurosurgical literature.
      During the 4-year period from July 1989 to June 1993, we placed fourth
      ventricular shunts in 12 patients. Remarkably, 5 patients suffered complications
      related to posterior fossa catheter placement (42% rate). Three of these patients
      developed new cranial nerve dysfunction caused by direct injury to the floor of
      the fourth ventricle, 1 patient suffered an intracystic hemorrhage and acute
      shunt malfunction, and 1 patient had the catheter tip in the brainstem on
      postoperative studies without new neurological deficit. We conclude that
      placement of fourth-ventricular shunts can be fraught with complications which we
      believe is related to technique. We propose that altering the trajectory of the
      ventricular catheter from our usual midline technique to a more lateral position
      will lessen the chances for injury to the floor of the fourth ventricle. In this
      manner we hope to decrease our incidence of complications for this procedure.

PMID- 7577667
TI  - Association of infantile neuroaxonal dystrophy and osteopetrosis: a rare
      autosomal recessive disorder.
AB  - The association of neuroaxonal dystrophy and osteopetrosis is reported in 2
      siblings born to non-consanguineous parents. The 1st child was diagnosed as
      having infantile osteopetrosis shortly after delivery. A computed tomography scan
      of the head revealed agenesis of the corpus callosum. She died at the age of 9
      months. Post-mortem examination showed pneumonia and bony sclerosis.
      Neuropathological examination revealed cerebral atrophy, ventricular dilation,
      absence of the corpus callosum, and a small hippocampus. Neuroaxonal spheroids
      were found in hippocampus, basal ganglia, pons, medulla, spinal cord, cranial
      nerves, cerebellum, and peripheral nerves. Ultrastructural examination revealed
      membranous cytoplasmic bodies and electron-dense granular deposits within the
      neuroaxonal spheroids as well as the soma of neurons. The 2nd child was delivered
      at 36 weeks of gestation because of intrauterine fetal distress. The diagnosis of
      osteopetrosis and partial agenesis of the corpus callosum was made shortly after
      delivery. The child died at 1 month without an autopsy. There are rare cases
      reported previously with the association of neuroaxonal dystrophy and
      osteopetrosis. We review these cases and compare them with ours.

PMID- 7577668
TI  - Klippel-Trenaunay-Weber syndrome with hydrocephalus: an unusual association.
AB  - Macrocephaly is an associated finding with Klippel-Trenaunay-Weber syndrome, the
      cause of which remains to be determined. Association of this syndrome with
      hydrocephalus due to aqueductal stenosis has not been reported previously in
      world literature and is presented in this clinical brief.

PMID- 7577669
TI  - Expression of type I and type IB receptors for activin in midgestation mouse
      embryos suggests distinct functions in organogenesis.
AB  - Activins exert their effects by inducing heteromeric complexes of either of two
      different type I receptors, ActR-I or ActR-IB, and either of two type II
      receptors, ActR-II or ActR-IIB. We describe the cDNA cloning of the mouse
      homologue of human ActR-IB and analyze binding of radio-iodinated activin on type
      I/type II combinations of mouse receptors expressed from cDNA. We studied the
      distribution of ActR-I and ActR-IB mRNAs in postimplantation mouse embryos by in
      situ hybridization. In the 12.5-day postcoitum embryo, both mRNAs are found in
      the brain, spinal cord, some ganglia, vibrissae, lungs, body wall, stomach,
      gonads, ribs, limbs and shoulders. ActR-I mRNA, but not ActR-IB, is expressed in
      blood vessels, the heart, tongue, intervertebral discs and diaphragm. Conversely,
      only ActR-IB mRNA is detected in the olfactory region, eye, tooth primordium,
      esophagus, mesonephros, dorsal root ganglia and is strongly expressed in the
      spinal cord. Our results demonstrate similarities, but also differences and
      complementarities (mesenchymal versus epithelial expression) between the
      expression patterns of these type I receptors. Moreover, their expression
      patterns overlap with at least one of the type II activin receptors and/or one of
      activin subunits in some regions of the embryo, such as the brain, spinal cord,
      pituitary, whisker follicles, and the inner nuclear neuroblastic layer of the
      eye.

PMID- 7577670
TI  - The expression of tyrosine hydroxylase and the transcription factors cPhox-2 and
      Cash-1: evidence for distinct inductive steps in the differentiation of chick
      sympathetic precursor cells.
AB  - The adrenergic differentiation of sympathetic neurons is controlled by complex
      interactions with the embryonic environment. To provide a basis for the
      experimental analysis of these interactions, the expression of the adrenergic
      marker enzyme tyrosine hydroxylase (TH) was analyzed by immunohistochemistry and
      in situ hybridization in sympathetic ganglia and the adrenal medulla of chick
      embryos. In parallel, the developmental expression of the transcription factors
      cPhox-2 and Cash-1 was analyzed by in situ hybridization. TH protein was first
      detectable during the third day of development (stage 19) in cells of the primary
      sympathetic strands. A few hours earlier (stage 18), TH mRNA could be found by in
      situ hybridization. At the very same time and location, mRNA for the
      transcription factor cPhox-2 was first observed. In contrast, mRNA for the
      transcription factor Cash-1 was detected much earlier, at stage 15, dorsal to the
      aorta where the primary sympathetic ganglia form. High TH mRNA levels are
      maintained during later embryonic development (stage 35) in both sympathetic
      ganglia and adrenal chromaffin cells. In contrast, cPhox-2 and Cash-1 mRNA are
      selectively reduced in chromaffin cells and sympathetic ganglia, respectively.
      The results show that TH and cPhox-2 are early markers expressed in sympathetic
      ganglia. Their coordinated expression points towards an inductive event possibly
      occurring close to the aorta and leading to the expression of an adrenergic
      phenotype. Cash-1 is detected significantly earlier, suggesting that its
      expression is induced by a separate event.

PMID- 7577671
TI  - The Drosophila cubitus interruptus protein and its role in the wingless and
      hedgehog signal transduction pathways.
AB  - The segment polarity gene cubitus interruptus (ci) is required to maintain
      expression of the wingless gene and to specify naked cuticle within each
      epidermal segment. Antibodies were generated against the ci protein and used to
      analyze its pattern of expression. By stage 11, post-transcriptional regulation
      of ci is observed. ci transcript levels are uniform across the anterior
      compartment, but protein levels are higher next to the compartment boundaries.
      The distribution of the ci protein is altered in fused, hedgehog and wingless
      mutants suggesting cell-cell signaling may regulate ci protein levels. The role
      of ci in cell-cell signaling and pattern formation was examined in double mutants
      of ci with patched and zeste-white3/shaggy.

PMID- 7577672
TI  - The expression pattern of Xenopus Mox-2 implies a role in initial mesodermal
      differentiation.
AB  - We have isolated a Xenopus homolog of the murine Mox-2 gene. As is the case for
      the mouse homolog, mesoderm specific expression of Xenopus Mox-2 (X. Mox-2)
      expression begins during gastrulation. Using whole mount in situ hybridization,
      we show that X. Mox-2 is expressed in undifferentiated dorsal, lateral and
      ventral mesoderm in the posterior of neurula/tailbud embryos, with expression
      more anteriorly detected in the dermatomes. In the tailbud tadpole, X. Mox-2 is
      expressed in tissues of the tailbud itself that represent a site of continued
      gastrulation-like processes resulting in mesoderm formation. X. Mox-2 is not
      expressed in the marginal zone of blastula, nor in the dorsal lip of gastrula,
      nor midline tissues (i.e. prospective notochord). Treatments that affect
      mesodermal patterning during embryonic development, including LiCl and
      ultraviolet light, and injection of mRNAs encoding BMP-4, or dominant negative
      activin and FGF receptors, produce changes in X. Mox-2 expression consistent with
      the types of tissues affected by these manipulations. X. Mox-2 expression is
      induced more in animal caps treated with FGF than those treated with activin.
      Together with the fact that X. Mox-2 activation in animal caps requires protein
      synthesis, our data suggest that X. Mox-2 is involved in initial mesodermal
      differentiation, downstream of molecules affecting mesoderm induction and
      determination such as Brachyury and goosecoid, and upstream of factors
      controlling terminal differentiation such as MyoD and myf5. X. Mox-2, therefore,
      is another useful marker for understanding the formation of mesoderm in amphibian
      development.

PMID- 7577673
TI  - Pax-2 expression in the murine neural plate precedes and encompasses the
      expression domains of Wnt-1 and En-1.
AB  - In the Drosophila embryo, activation of wingless and engrailed in the parasegment
      requires paired, a member of the Pax family of transcription factors. We have
      explored the possible conservation of this regulatory hierarchy in the developing
      mouse brain. We find that Pax-2 is expressed prior to somite formation in the
      presumptive mid/hindbrain region. Shortly thereafter, Wnt-1 (the wingless
      orthologue) and Engrailed-1 are expressed in overlapping regions within the Pax-2
      domain. Pax-5 expression commences later, at the 3-somite stage. Thus, the
      spatial and temporal expression of Pax-2 is consistent with a possible regulatory
      role in the activation of Wnt-1 and En-1.

PMID- 7577674
TI  - Inhibition of Xhox1A gene expression in Xenopus embryos by antisense RNA produced
      from an expression vector read by RNA polymerase III.
AB  - Antisense inhibition of gene expression during Xenopus development was obtained
      by injecting, into the zygote, an expression vector carrying the adenovirus VAI
      gene read by RNA polymerase III. This vector yields high levels of antisense RNA
      in most embryonic cells between mid-blastula transition and tailbud stage. As a
      target we chose the Xenopus homeobox gene Xhox1A. A 26 bp long oligonucleotide,
      including the initiation codon of this gene, was inserted in opposite polarity
      into the vector. Antisense treatment reduces Xhox1A mRNA in embryos up to stage
      22 and Xhox1A protein expression up to stage 30. Half of the antisense-treated
      embryos develop a characteristic phenotype with disorganized somites in the
      anterior trunk and delayed development of the intestinal tract.

PMID- 7577675
TI  - Expression patterns of the paired-related homeobox genes MHox/Prx1 and S8/Prx2
      suggest roles in development of the heart and the forebrain.
AB  - Prx1 and Prx2 (previously called MHox and S8, respectively) are the members of a
      small subfamily of vertebrate homeobox genes expressed during embryogenesis from
      gastrulation onwards. We directly compared the expression domains of the Prx
      genes in detail in mouse and in addition some aspects of these patterns in
      chicken. In addition to the superficially similar expression patterns of Prx1 and
      Prx2 in cranial mesenchyme, limb buds, axial mesoderm, and branchial arches and
      their derivatives, we detect major differences at many sites particularly in
      heart and brain. Our analysis indicated in several cases a correlation with
      regions developing into connective tissues. From at least day 8.5, Prx-1
      expression was observed in the heart, initially in the endocardial cushions and
      later in the developing semilunar and atrioventricular valves. Prx2 develops
      early on a diffuse myocardial expression pattern and is later higher expressed in
      the ventricular septum and in particular in the ductus arteriosus. Prx2 is never
      expressed in the brain, whereas Prx1 is expressed, from at least day 9.5 onwards,
      in a unique distinct domain in the ventral part of the hypothalamus, as well as
      in a broader region of the telencephalon.

PMID- 7577676
TI  - Two otu transcripts are selectively localised in Drosophila oogenesis by a
      mechanism that requires a function of the otu protein.
AB  - The ovarian tumour gene (otu) is required for several processes during Drosophila
      oogenesis. The locus encodes two protein isoforms that have been proposed to act
      during different stages of oogenesis. Here we show that the corresponding otu
      mRNAs display a dynamic pattern of expression during oogenesis. The 4.1 kb mRNA
      encoding the 104 kDa isoform is expressed throughout adult oogenesis, but is
      mainly restricted to nurse cells. The 3.2 kb mRNA encoding the 98 kDa protein
      isoform is selectively localised in the oocyte up to stage 9. Both mRNAs are
      expressed abundantly in nurse cells at stages 10-11. We propose that the oocyte
      specific function of otu is realised by the 98 kDa isoform. We show that the
      export of the 3.2 kb mRNA from the nurse cell nuclei requires a functional otu
      protein. The otu protein is also required for the correct distribution of the
      pumilio and oskar mRNAs, while the Bic-D, K10 and staufen mRNAs are localised in
      wild type fashion in otu mutants. Furthermore, we have observed a region of
      homology between the carboxy-terminal part of the otu protein and the mammalian
      microtubule associated proteins. The more severe the mutation in this region of
      homology, the more disturbed mRNA distribution is observed in otu mutants.

PMID- 7577677
TI  - The Drosophila extra sex combs protein contains WD motifs essential for its
      function as a repressor of homeotic genes.
AB  - Extra sex combs is a member of the Polycomb Group genes, whose products are
      required for stable long term transcriptional repression of the homeotic genes of
      the Bithorax and Antennapedia complexes. The Pc-G proteins are required to
      maintain the spatially restricted domains of homeotic gene expression established
      by the transiently expressed repressors, e.g., hunchback, but are not required
      for the functioning of these early repressors. This implies two distinct modes of
      repression and raises the question: how does the transition from early transient
      repression to stable Pc-G-mediated repression occur? While other Pc-G proteins
      are required continuously throughout development, the esc RNA is only present
      transiently in early embryos, suggesting that esc may play a role in mediating
      this transition to stable long term Pc-G-mediated repression. The predicted esc
      protein contains multiple copies of the WD motif, found in G-protein beta
      subunits as well as non-G proteins involved in diverse cellular functions,
      including transcriptional repression. The sequence alterations of a number of esc
      mutations cause amino acid substitutions within the WD repeats, identifying them
      as essential for the function of the esc protein as a repressor of homeotic gene
      expression. Other WD proteins are components of reversible macromolecular
      assemblies and the WD motif has recently been directly implicated in mediating
      interactions with other proteins in such complexes. We propose that the esc
      protein is similarly involved in the initial recruitment of Pc-G repressors to
      the homeotic genes to establish their stable long term repression.

PMID- 7577678
TI  - Trithorax is required to maintain engrailed expression in a subset of engrailed
      expressing cells.
AB  - We show that maintenance but not initiation of engrailed (en) gene expression in
      the Drosophila embryo requires trithorax (trx), which is also required to
      maintain stable long-term expression of the homeotic genes throughout the
      development. Like the homeotic genes, en expression is dependent on trx in only a
      subset of embryonic cells normally expressing en, including specific cells in the
      nervous system and the dorsal fat body cells surrounding the gonad. Loss of en
      expression in the dorsal fat body is correlated with the sterility of en females
      which also carry trx mutations. In addition, trx is required for normal en
      expression in the posterior compartment of the developing wing, reflected in
      enhancement of en phenotypes in en adults which also carry trx mutations. trx
      appears to be dispensable for maintenance of en expression in other embryonic
      cells. The trx protein binds to the region of the polytene chromosomes which
      contains the en gene, suggesting that trx regulates en expression directly by
      binding to the en regulatory region.

PMID- 7577679
TI  - Wnt expression patterns in chick embryo nervous system.
AB  - Several lines of evidence suggest that Wnt genes play a critical role in
      regulating development of the vertebrate embryo. To address the role that this
      family may play in the development of the chicken central nervous system (CNS),
      we have used a PCR based strategy to clone partial sequences for Wnt genes. At
      least six different Wnt genes are expressed in the developing CNS of the chick
      embryo. The domains of expression overlap either partially or completely, and are
      expressed in spatial domains that prefigure morphological subunits of the
      embryonic neural tube. Wnt-1 and Wnt-4 are first expressed in the open neural
      plate in the region of the presumptive mesencephalon. Wnt-3a expression is first
      observed in the rhombencephalic regions of the open neural plate. After neural
      tube closure, when the embryonic subdivisions of the neural tube became apparent,
      Wnt-1, Wnt-3a and Wnt-4 are all broadly expressed in partially overlapping
      domains in the mesencephalon and caudal diencephalon, as well as in the
      rhombencephalon and spinal cord. The mesencephalic expression patterns are
      subsequently modified such that Wnt-1 and Wnt-4 are expressed in a characteristic
      ring just rostral to the isthmus, at the mesencephalic/metencephalic junction;
      and Wnt-1 and Wnt-3a expression become restricted to the dorsal midline. Wnt-1,
      Wnt-3a, Wnt-4, Wnt-5a and Wnt-8b are expressed in one or two caudal subdivisions
      of the developing diencephalon, the synencephalon and posterior parencephalon,
      but do not extend ventral to the zona limitans interparencephalica. In contrast,
      Wnt-7b is expressed in the anterior parencephalon. Both Wnt-7b and Wnt-8b are
      expressed in telencephalic portions of the secondary prosencephalon. The timing
      and spatial distribution of Wnt-gene expression in the chick embryo further
      support the general hypothesis that Wnt genes play key roles in patterning the
      developing vertebrate nervous system.

PMID- 7577680
TI  - Hox gene products modulate the DNA binding activity of Pbx1 and Pbx2.
AB  - A new family of homeodomain proteins has recently been identified that includes
      extradenticle, ceh-20 and three mammalian proteins Pbx1, Pbx2 and Pbx3. We show
      here that two members of this family, Pbx1 and Pbx2 bind cooperatively to DNA
      with both Hoxb-7 and Hoxb-8. Engrailed-2 modulates the DNA binding activity of
      the Pbx proteins to a different target site. E2A-Pbx1, a chimeric Pbx1 gene
      product involved in pre-B acute lymphoblastoid leukemia, has retained its ability
      to interact with the Hox proteins. These data show that vertebrate Hox and Pbx
      gene products have the ability to bind cooperatively to DNA.

PMID- 7577681
TI  - Oscillation in physiological regulation.

PMID- 7577682
TI  - Discrete, patterned and purposeful adaptive physiological adjustments integrated
      by forebrain influences.

PMID- 7577683
TI  - Spectral indices of cardiovascular adaptations to short-term simulated
      microgravity exposure.
AB  - We investigated the effects of exposure to microgravity on the baseline autonomic
      balance in cardiovascular regulation using spectral analysis of cardiovascular
      variables measured during supine rest. Heart rate, arterial pressure, radial
      flow, thoracic fluid impedance and central venous pressure were recorded from
      nine volunteers before and after simulated microgravity, produced by 20 hours of
      6 degrees head down bedrest plus furosemide. Spectral powers increased after
      simulated microgravity in the low frequency region (centered at about 0.03 Hz) in
      arterial pressure, heart rate and radial flow, and decreased in the respiratory
      frequency region (centered at about 0.25 Hz) in heart rate. Reduced heart rate
      power in the respiratory frequency region indicates reduced parasympathetic
      influence on the heart. A concurrent increase in the low frequency power in
      arterial pressure, heart rate, and radial flow indicates increased sympathetic
      influence. These results suggest that the baseline autonomic balance in
      cardiovascular regulation is shifted towards increased sympathetic and decreased
      parasympathetic influence after exposure to short-term simulated microgravity.

PMID- 7577685
TI  - The Pavlovian "principle of strength".
AB  - The Pavlovian principle of strength assumed that the magnitude of the conditional
      response is a linear function of the intensity of the external conditional
      stimulus. But experiments failed to provide evidence for the universality of the
      principle. The Pavlovians tried to identify conditions that distorted the
      linearity of this relationship. Some of the disturbing conditions were external
      and some were internal intervening variables. It is possible that the relation
      between the strength of the conditional stimulus and the magnitude of the
      conditional response is not linear but logarithmic. Pavlov acknowledged the lack
      of experimental evidence to support the principle of strength in its original
      form.

PMID- 7577684
TI  - Forebrain involvement in fatal cardiac arrhythmia.

PMID- 7577686
TI  - W. Horsley Gantt--a legend in his time.

PMID- 7577687
TI  - The social sciences and medicine.

PMID- 7577688
TI  - Odontological identification of the victims of flight AI. IT 5148 air disaster
      Lyon-Strasbourg 20.01.1992.
AB  - The authors report on the contribution of odontological identification of the
      flight AI. IT 5148 air disaster victims, which occurred on 20th January 1992. The
      identification procedure was difficult due to large numbers of bodies and
      mutilations and required the involvement of multidisciplinary teams composed of
      odontologists, forensic pathologists, radiologists and biologists. The authors
      set up a simple, discriminant classification which was easy to handle by a
      multidisciplinary team. Four groups were defined according to the matching
      characteristics between ante and post mortem data. Perfect matching
      characteristics between ante and post mortem data were achieved in only 44 cases
      (Group A). Partial matching characteristics between ante and post mortem data
      were achieved in 12 cases (Group B). In 29 cases, the insufficiency or absence of
      odontological data (Group C and D) did not enable the victim to be identified.
      The results of the investigations showed that the dental examination alone
      enabled 17 victims to be identified and by including a morphological examination
      the figure reached 33. By the end of the investigations, 85 of the 87 victims
      were positively identified. Odontological identification is an essential,
      accurate and rapid method with allows a body to be identified from its dental
      characteristics. This anthropometrical method of identification is included with
      the descriptive and the biological methods. The authors present their experience
      in performing a formal identification of 44 victims in less than 15 days.

PMID- 7577689
TI  - Detection of T to G mutation at position 59 in the Lewis gene by mismatch
      polymerase chain reaction.
AB  - Recently, we discovered the missense mutations of T to G at position 59 and of G
      to A at position 508 in one of the Lewis-negative (le) genes (Koda et al. 1993).
      In the present study, we report a method to detect the mutation at position 59
      using mismatch PCR amplification and endonuclease MspI digestion. For this
      mutation, we found that 7 out of 12 Lewis-negative, and none of 15 Lewis-positive
      individuals were homozygous, while 4 out of 12 Lewis-negative, and 4 out of 15
      Lewis-positive individuals were heterozygous. These results indicate that the
      mutation at position 59 is a common mutation in the le genes.

PMID- 7577691
TI  - CMV-DNA detection in parenchymatous organs in cases of SIDS.
AB  - A nested PCR approach has been developed especially for the detection of small
      amounts of cytomegalovirus (CMV) DNA in autopsy samples. Lung tissue and
      submandibular glands in 118 cases of infant death (92 SIDS cases, 13 natural
      deaths due to other defined causes and 13 unnatural deaths) were investigated by
      this technique and compared to the results obtained by other CMV detection
      methods (histology, immunohistochemistry, in situ hybridization and PCR). CMV-DNA
      could be detected in the lung tissue in 7 cases of SIDS using nested PCR.
      Compared to conventional PCR (3 positive cases in lung tissue) the nested
      approach always gave glear results and showed less additional bands. In all cases
      where CMV could be detected in the lungs, positive results were also obtained in
      the submandibular glands. The nested PCR method proved to be a more sensitive
      technique than the other detection methods including PCR and hot start, and even
      minimal amounts of target DNA could be detected in the presence of human and
      bacterial background DNA.

PMID- 7577690
TI  - The use of the STRs HUMTH01, HUMVWA31/A, HUMF13A1, HUMFES/FPS, HUMLPL in forensic
      application: validation studies and population data for Galicia (NW Spain).
AB  - The 5 tetranucleotide short tandem repeats, HUMTH01, HUMVWA31/A, HUMF13A1,
      HUMFES/FPS and HUMLPL were studied using different electrophoretic methods and
      PCR amplification conditions in order to optimize the typing conditions. A
      genetic population study in the population of Galicia was carried out and the
      allele and genotype frequencies are given. Compliance with the Hardy-Weinberg
      equilibrium was tested using different statistical parameters, with clear
      advantages resulting in favor of using the exact test (Guo-Thompson method)
      instead of conventional chi-square methods. Some statistical parameters of
      forensic interest (PD, CE, h) were also calculated. There were no mutations found
      in a total of 73 paternal meioses and 101 maternal meioses. Abnormal
      electrophoretic mobility was found in the AT-rich STR HUMF13A1 under non
      denaturing conditions and, therefore, the use of denaturing conditions is
      absolutely necessary. No "stutter" bands were found, although double peaks in the
      HUMFES/FPS system were observed in some samples. The advantage of using automated
      sequencers with fluorescent technology is also reported.

PMID- 7577692
TI  - Diagnosis of HIV infection from bloodstains by PCR. A further marker for
      identification.
AB  - The forensic usefulness of the detection of HIV infection in bloodstains is
      linked to the increasing spread of HIV infection and the consequent rise in the
      number of forensic cases involving HIV-positive subjects. This study was designed
      to detect HIV infection in bloodstains of various ages obtained from HIV-positive
      patients treated with zidovudine (3'-azido-3'-deoxythymidine, AZT) using PCR
      methods. Of the 3 kinds of extraction and amplification methods checked, only a
      nested PCR method for the amplification of a sequence located in the HIV Reverse
      Transcriptase (RT) region was successful. This method, involving 2 amplification
      steps (1: fragment of 768 bp; 2: codons 41-67-70-215-219), encompasses the
      mutations commonly observed during AZT therapy and overcomes the limitations
      inherent in serological testing. The discriminatory power of the method can
      detect specific mutation patterns in the RT gene linked to drug resistance and
      compares the specific pattern of the blood-stain with fresh blood or other
      specimens from the subject in question.

PMID- 7577693
TI  - Ultrastructural alterations and environmental exposure influence the opiate
      concentrations in hair of drug addicts.
AB  - Hair samples were taken at autopsy from the head of 1 male and 1 female subject
      both known as drug abusers. Some of the strands were bleached by in-vitro
      cosmetic treatment. The bleached hair as well as the original hair samples were
      partly exposed to water or soil prior to further investigations and drug
      monitoring. The exposure times were 4 weeks or 6 months for water and 6 months
      for soil. The hair fibers were examined by transmission electron microscope (TEM)
      and by scanning electron microscope (SEM) investigations. The electron microscope
      studies confirmed that all experimental conditions had produced morphological
      alterations in the hair fibers. After exposure to water or to soil for 6 months
      as well as after storage of the clipped bleached hair in tap water at room
      temperature for 4 weeks, drug monitoring of formerly positive hair samples gave
      negative results. After storage of natural hair in soil or in water for 4 weeks
      the opiate levels had dramatically decreased. The samples were screened by
      fluorescence polarization immunoassay after enzymatic digestion. The results were
      confirmed by GC/MS.

PMID- 7577694
TI  - Use of the National Register of medico-legal autopsies in epidemiological suicide
      research.
AB  - Finnish forensic pathologists have been keeping their own National Register of
      medicolegal autopsies (NRMA) since 1985. The aims of this work were to determine
      the reliability of this register by comparing the data with the cause-of-death
      statistics published by the Central Statistical Office of Finland (CSO) and to
      assess its usefulness for epidemiological forensic research. The
      comprehensiveness of the register over the period 1986-1991 was studied in
      general terms and tested by checking the inclusion of known suicides by
      physicians during that period. Coverage of the NRMA concerning definite suicides
      was 97% as compared with the cause-of-death statistics of the CSO. The conclusion
      is that the NRMA is reliable enough to allow changes in causes and manners of
      death to be examined in the relatively small homogeneous population of Finland.
      One of the NRMA's advantages is it's direct and rapid accessibility to different
      mortality data.

PMID- 7577695
TI  - A simple analysis of 5 thinner components in human body fluids by headspace solid
      phase microextraction (SPME).
AB  - A simple method for the extraction of 5 thinner components from human whole blood
      and urine, using the headspace solid-phase microextraction (SPME) method is
      presented. After heating a vial containing the samples with 5 compounds (toluene,
      benzene, n-butyl acetate, n-butanol and n-isoamyl acetate) at 80 degrees C, a
      polydimethylsiloxane-coated SPME fiber was exposed to the headspace of the vial
      to allow adsorption of the compounds. The fiber needle was then injected into a
      capillary gas chromatography (GC) port. The headspace SPME-GC gave intense peaks
      for each compound and a low level of background noise was seen only for whole
      blood. Recovery rates of the 5 compounds by use of the headspace SPME-GC were 50
      70%. Reproducibility for headspace SPME-GC data were excellent for both body
      fluids. The calibration curves showed linearity in the range 2-100 ng/0.5 ml
      whole blood or urine. The detection limits of each compound were 1.1-2.4 ng/0.5
      ml sample. The present results on the analysis of 5 thinner components by
      headspace SPME-GC suggest its applicability to a number of other volatile
      compounds in forensic toxicology.

PMID- 7577697
TI  - Suicide with a signal pen gun.
AB  - A man committed suicide with a modified signal pen gun and a .22 lr HV HP bullet.
      The contact shot to the left chest led to a conventional entrance wound. The
      projectile from the unconventional weapon caused a penetrating wound and was not
      deformed instead of the expected perforation and deformation. The smooth-bore
      barrel did not leave characteristic firing marks on the bullet.

PMID- 7577696
TI  - Phenotype differences of STRs in 7 human populations.
AB  - A maximum of 6 STR systems (TH01, VWA, ACTBP2, FES, F13B, D21S11) was
      investigated in 7 human populations (Germans, Turks, Moroccans, Japanese,
      Chinese, Papuans, Ovambos). In each population no deviations from Hardy-Weinberg
      equilibrium were observed. Out of each population the phenotypes of 50
      individuals (comprising 3 to 6 STRs) were randomly selected. Based on the
      phenotype frequencies interpopulation comparisons were carried out using the
      frequencies of each other population. Within major ethnic groups only minor
      differences in phenotype frequencies were found. Between major ethnic groups
      differences of up to several orders of magnitude could be observed. The most
      discriminative STRs for interpopulation comparisons were TH01, FES and F13B.

PMID- 7577698
TI  - Traumatic origin of a meningioma?
AB  - The case of a 41-year-old pregnant woman is reported who was found dead in her
      apartment 5 months after she had suffered a severe head injury due to a car
      accident. An autopsy, a meningioma (4 cm in diameter) was found localized in the
      right parieto-temporal region which had probably caused an epileptic seizure
      leading to central dysfunction and to death. The criteria concerning the
      diagnosis of a traumatic meningioma are discussed. In the present case, a causal
      connection between a former head trauma and the development of the tumor had to
      be refuted.

PMID- 7577699
TI  - A study of the short tandem repeat systems HUMVWA and HUMTH01 in an Austrian
      population sample.
AB  - The genotype distributions for the short tandem repeat systems (STRs) HUMVWA and
      HUMTH01 have been studied in 128 unrelated Caucasians fromeAustria. The allelic
      distributions were in accordance with Hardy-Weinberg expectations. The
      heterozygosities were 0.82 and 0.81, whereas the mean exclusion chance was 0.62
      and 0.55, respectively. In one person, a VWA-allele consisting of 11 repeats was
      found.

PMID- 7577700
TI  - Differentiation of the expression of aldosterone synthase and 11 beta-hydroxylase
      mRNA in the rat adrenal cortex by reverse transcriptase-polymerase chain
      reaction.
AB  - The adrenocortical enzymes of the steroidogenic late pathway in the rat are
      aldosterone synthase (P450aldo), which catalyzes the production of aldosterone,
      and 11 beta-hydroxylase (P45011 beta), which catalyzes the production of
      corticosterone throughout the cortex. These two enzymes are highly homologous and
      are encoded by the genes CYP11B2 and CYP11B1, respectively. The purpose of the
      present study is to describe the development of two sets of primers and the
      reverse transcription-polymerase chain reaction (RT-PCR) conditions that are
      capable of discriminating between rat P450aldo and P45011 beta mRNAs. The
      P450aldo primer set did not amplify full length cDNA P45011 beta plasmid and the
      P45011 beta primer set did not amplify full length cDNA P450aldo plasmid
      indicating minimal crosstalk. The fidelity of the PCR primers and method was
      further established by sequencing the PCR products and demonstration of virtual
      identity with the published sequences of P450aldo and P45011 beta. RT-PCR of mRNA
      from adrenal capsules (zona glomerulosa) and subcapsules (zona
      reticularis/fasciculata) from rats demonstrated no effect of sodium diet on the
      expression of P45011 beta mRNA but an approximately 8-fold greater expresison in
      P450aldo mRNA on low vs high sodium intake. Similar results were found when
      single hemicapsules were subjected to RT-PCR, demonstrating the sensitivity of
      the method. We conclude that the two sets of PCR primers and the RT-PCR method
      described are capable of evaluating the expression of the highly homologous mRNAs
      for P450aldo and P45011 beta with great precision and sensitivity.

PMID- 7577701
TI  - Relationship between estrogen structure and conformational changes in estrogen
      receptor/DNA complexes.
AB  - The effect of estrogen structure on the conformation of the complex formed with
      estrogen receptor (ER) and the consensus estrogen response element (EREc) has
      been examined with gel mobility shift assay. Proteins in MCF-7 cell extracts
      formed three distinct complexes with ERE. Only the slowest moving complex
      contained ER as indicated by binding with anti-ER antibodies H222 and D547. This
      ER-ERE complex displayed increased electrophoretic mobility when formed in the
      presence of estradiol (E2) and bound radiolabeled 16 alpha-iodoestradiol. The
      antiestrogen ICI 164,384 decreased the mobility of the ER-ERE complex and blocked
      the effect of E2. The results reported here indicate that the position and
      location of hydroxyl groups on the estratriene nucleus is an important factor in
      determining the mobility of ER-EREc (or a variant ERE) in gel shift assays. The
      ability of E2 analogs to cause conformational changes detectable as altered
      mobility was not directly related either to their binding affinity for ER or to
      their ability to activate E2 responsive genes. Although several
      dihydroxyestrogens (estradiol-16 alpha, 1- and 2-hydroxyestratrien-17 beta-ol)
      caused an increase in the mobility of the ER-EREc, other ligands (estradiol-17
      alpha, 4-hydroxyestratriene-17 beta-ol, 3-hydroxy estratriene, estratrien-17 beta
      ol and 5-androsten-3 beta, 17 beta-diol) with a capacity for activating at least
      some E2 responsive genes in MCF-7 cells had little or no effect. On the basis of
      these and previously published results, it can be concluded that specific
      structure features of estrogens are responsible for conformational changes of ER
      ERE complexes detectable in gel-shift assays. Furthermore, the identified
      structural characteristics of the ligand which are required for gel-shift are not
      the same as those previously reported to be essential for stimulation of
      transcriptional activity of ER.

PMID- 7577702
TI  - Alteration of the expression of human estrogen receptor gene by distamycin.
AB  - The effects of distamycin on the expression of the estrogen receptor gene were
      determined in the MCF7 human breast cancer cell line. Estrogen receptor (ER) RNA
      transcripts were analyzed by Northern blotting and RT-PCR using specific
      oligonucleotides for the 5' upstream region and for ER cDNA. After ex vivo
      distamycin treatment of the cells the expression of the canonical ER mRNA isoform
      of 6.3 kb is strongly inhibited, without appreciable alteration of the
      accumulation of 5' upstream ER mRNA isoforms. These results suggest that
      distamycin alters the transcriptional activity of the ER gene causing a change in
      the ratio between the canonical transcript and other isoforms containing 5'
      upstream regions.

PMID- 7577703
TI  - Tandem immunoaffinity chromatography for plasma 1 alpha,25-dihydroxyvitamin D3
      utilizing two antibodies having different specificities: a novel and powerful
      pretreatment tool for 1 alpha,25-dihydroxyvitamin D3 radioreceptor assays.
AB  - We report here a novel and powerful pretreatment method for radioreceptor assays
      (RRAs) for human plasma 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) based on
      "Tandem" immunoaffinity chromatography (Tandem IAC). Two antibodies having
      different specificities were each immobilized on agarose gel with cyanogen
      bromide to produce immunosorbents which were stable and repeatedly usable. An
      ethyl ether extract of plasma was applied to the first affinity column, from
      which 1,25(OH)2D3 could be preferentially eluted and separated from 1 alpha-deoxy
      type metabolites. The effluent was then submitted to the second column, and the
      1,25(OH)2D3 retained was eluted after non- or weakly-absorbed interfering
      substances were washed out. This procedure allowed efficient purification without
      careful handling or strict time-management in the entire operation and enabled
      avoiding preparative high-performance liquid chromatography (HPLC) from RRA even
      with a conventional chick intestinal vitamin D receptor. Mean (+/- SD) plasma
      1,25(OH)2D3 values of 56 normal subjects and 10 patients with chronic renal
      failure, obtained with this Tandem IAC/RRA system, were 36.4 (8.7) and 11.2 (4.0)
      pg/ml, respectively. The Tandem IAC will also be useful for developing
      immunoassays or gas chromatography-mass spectrometry of 1,25(OH)2D3.

PMID- 7577704
TI  - Transport of dehydroepiandrosterone and dehydroepiandrosterone sulphate into rat
      hepatocytes.
AB  - The purpose of the present study was to characterize the transport of
      dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) into
      hepatocytes at physiological and pharmacological concentrations. Hepatocytes were
      isolated from female Sprague-Dawley rats by collagenase perfusion. Uptake of
      [3H]DHEA and [3H]DHEAS at increasing concentrations (3.5 nM-100 microM) was
      measured by the rapid filtration technique at 30 s intervals up to 120 s. The
      uptake of DHEAS by hepatocytes was saturable (Km = 17.0 microM; Vmax = 3.7
      nmol/min/mg cell protein). In contrast, a specific saturable transport system for
      DHEA could not be detected in rat hepatocytes. It is suggested that DHEA enters
      the cell by diffusion. The uptake of DHEAS could be inhibited by antimycin A,
      carbonylcyanide-m-chlorophenylhydrazone, and dinitrophenol (inhibitors of the
      mitochondrial respiratory chain), by dinitrofluorobenzene and p
      hydroxymercuribenzoate (NH2- and SH-blockers, respectively), and by monensin
      (Na(+)-specific ionophore). No inhibition was seen in the presence of ouabain
      (inhibitor of Na(+)-K(+)-ATPase) and phalloidin (inhibitor of cholate transport
      and actin-blocker). Interestingly, DHEAS uptake was inhibited by bile acids
      (cholate, taurocholate and glycocholate). Conversely, [3H]cholate uptake was
      strongly inhibited by DHEAS, which indicates a competition for the same carrier.
      Replacement of sodium ion with choline markedly decreased uptake velocity at
      pharmacological DHEAS concentrations. The results suggest that DHEAS uptake is a
      saturable, energy-dependent, carrier-mediated, partially Na(+)-dependent process,
      and that DHEAS may be taken up via the multispecific bile acid transport system.

PMID- 7577706
TI  - Requirement for heparan sulphate proteoglycans to mediate basic fibroblast growth
      factor (FGF-2)-induced stimulation of Leydig cell steroidogenesis.
AB  - This study reports that, in contrast to previous findings, basic fibroblast
      growth factor (FGF-2) stimulates immature Leydig cell steroidogenesis in the
      absence of luteinizing hormone (LH). Heparan sulphate proteoglycans (HSPGs) are
      essential for this action of FGF-2 and the data suggest that HSPG/FGF-2
      interactions have a significant role in the maintenance of immature Leydig cell
      steroidogenesis. Culture conditions were established for the maintenance of
      immature rat Leydig cells steroidogenesis in vitro for at least 2 days. Under
      these conditions the effect of exposure to FGF-2 at doses ranging from 0.1-10
      ng/ml was shown to cause a significant stimulation of basal, but not LH
      stimulated, 5 alpha-androstane 3 alpha,17 beta-diol production over 24h in
      culture. This stimulatory action on basal steroidogenesis is mediated through
      HSPG, as it was blocked by the addition of heparin (100 micrograms/ml), sodium
      chlorate (25mM) and protamine sulphate (5 micrograms/ml). These data demonstrate
      the involvement of HSPG in regulating FGF-2 action on Leydig cells and a
      potential role for Leydig cell HSPG in mediating paracrine regulatory actions of
      other heparin binding growth factors.

PMID- 7577705
TI  - Differential dynamics of receptor down-regulation and tyrosine aminotransferase
      induction following glucocorticoid treatment.
AB  - Autoregulation of glucocorticoid receptor (GR) concentration in vivo may be an
      important determinant of steroid sensitivity. The dynamics of GR regulation were
      assessed and compared to regulation of tyrosine aminotransferase (TAT) expression
      in liver tissue taken from rats treated with a single 50 mg/kg i.v. dose of
      methylprednisolone. Plasma methylprednisolone concentrations were determined by
      HPLC analysis. Receptor and TAT message levels were determined by quantitative
      Northern hybridization. Methylprednisolone plasma kinetics showed a half-life of
      0.6 h. Receptor occupancy occurred rapidly and cytosolic GR reappeared over 2-12
      h. TAT activity rose between 2 and 6 h and then dissipated. Reduction in receptor
      mRNA levels occurred very rapidly, being detectable by 30 min following steroid
      administration. A down-regulated steady-state in GR message expression was
      reached by 2 h post-injection, and was maintained throughout the 18 h examined in
      this study. Comparison of methylprednisolone kinetics demonstrated that down
      regulation was maintained long after drug was eliminated. In contrast, TAT
      message induction occurred with a sharp peak; maximal induction occurred between
      5-6 h and return to baseline at approx. 8-10 h post-induction. This study shows
      that unlike TAT induction, GR message repression in vivo does not require
      continual presence of hormone.

PMID- 7577708
TI  - Direct expression of pig testicular 3 alpha/beta (20 beta)-hydroxysteroid
      dehydrogenase in Escherichia coli.
AB  - The cDNA coding for pig testicular 3 alpha/beta (20 beta)-hydroxysteroid
      dehydrogenase was expressed in Escherichia coli by placing it under the control
      of an isopropylthiogalactoside (IPTG) inducible tac promoter. Production of 3
      alpha/beta (20 beta)-HSD was demonstrated by Western blotting and by catalytic
      activity with 5 alpha-dihydrotestosterone as a substrate for 3 alpha/beta-HSD,
      and progesterone and 17 alpha-hydroxyprogesterone as substrates for 20 beta-HSD
      in the presence of NADPH. The 3 alpha/beta (20 beta)-HSD enzyme was detected in a
      soluble fraction of the lysate of E. coli added to IPTG to induce the synthesis
      of the protein. Its molecular weight was estimated to be 30.5 kDa by SDS
      polyacrylamide gel electrophoresis (SDS-PAGE). Recombinant 3 alpha/beta (20 beta)
      HSD was purified to apparent homogeneity as determined by SDS-PAGE by column
      chromatography using DEAE-cellulose. The purified enzyme reduced not only
      steroids but also prostaglandins and other carbonyl compounds including
      aldehydes, ketones and quinones as demonstrated in native enzymes purified from
      pig testes. The amino terminus of the purified enzyme was serine which was coded
      next to the ATG start codon, and the sequence of the amino terminal 24 residues
      was identical with the coding amino acid in the cDNA; whereas, the amino terminus
      of the native 3 alpha/beta (20 beta)-HSD was not detected suggesting that the N
      terminal amino acid was blocked.

PMID- 7577707
TI  - Corticotropin releasing factor decidualizes human endometrial stromal cells in
      vitro. Interaction with progestin.
AB  - Decidualization of endometrial cells is a hormone-dependent process of
      differentiation which occurs during the menstrual cycle and pregnancy. Recent in
      vitro studies have revealed that cAMP and its generators induce decidualization
      of stromal cells isolated from proliferative endometrium and that progestins
      enhance the effect of cAMP. Since corticotropin releasing factor (CRF) generates
      cAMP and prostaglandins in other organs, in the present study the effect of CRF,
      a hypothalamic factor also produced by decidua and fetal membranes, on in vitro
      decidualization of endometrial stromal cells was evaluated. The addition of CRF
      to a culture medium of stromal cells induced in vitro decidualization, as
      indicated by morphologic changes from elongated fibroblast-like cells into larger
      and round cells and by the release of prolactin in the medium. The effect of CRF
      on stromal cells and on prolactin release was significantly augmented by the
      coincubation in the presence of medroxyprogesterone acetate. This observation
      indicates CRF as a novel factor of decidualization and confirms that progestins
      act as enhancers of the expression of decidual products.

PMID- 7577710
TI  - Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of
      selective inhibitors.
AB  - The present study describes the independent expression of the type 1 and 2
      isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell
      expression system and the selectivity of their inhibition. The catalytic
      properties and kinetic parameters of the recombinant isozymes were consistent
      with published data. The type 1 isoform displayed a neutral (range 6-8) pH
      optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had
      higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9
      microM, respectively). Finasteride and turosteride were selective inhibitors of
      the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108
      and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens
      (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2
      micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml,
      respectively). The three azasteroids were competitive inhibitors vs substrate,
      whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and
      uncompetitive inhibition of the type 2 isozyme. These observations suggest that
      the lipid component of LSESr might be responsible for its inhibitory effect by
      modulating the membrane environment of 5 alpha-reductase. Partially purified
      recombinant 5 alpha-reductase type 1 activity was preserved by the presence of
      lipids indicating that lipids can exert either stimulatory or inhibitory effects
      on human 5 alpha-reductase.

PMID- 7577709
TI  - The potent and selective inhibition of estrogen production by non-steroidal
      aromatase inhibitor, YM511.
AB  - YM511 inhibited aromatase activities in microsomes from rat ovary and human
      placenta competitively (IC50s: 0.4 and 0.12 nM, respectively). YM511 was about 3
      times more potent than other aromatase inhibitors, such as CGS 16949A, CGS 20267
      and R 76713. YM511 decreased the contents of estradiol stimulated by pregnant
      mare's serum gonadotropin in rat ovary with an ED50 of 0.002 mg/kg, indicating
      that YM511 was equipotent to CGS 20267 and 3 times more potent than the other two
      inhibitors. Serum estradiol levels in female rats were reduced by YM511 at 0.01
      mg/kg into the ovariectomized range. YM511 at 1 mg/kg for 2 weeks decreased rat
      uterine weight to levels comparable to ovariectomy, showing it was 10 times more
      potent than other inhibitors. But the maximal inhibitory effect of tamoxifen
      failed to reach ovariectomized level. YM511 slightly inhibited production of
      other steroid hormones in vitro and in vivo. The IC50s of YM511 for aldosterone
      and cortisol production from adrenal cells were from 5500 to 9800 times higher
      than that for rat ovarian aromatase and 130,000 times higher for testosterone
      production, indicating that YM511 is a highly specific aromatase inhibitor. The
      data suggest that YM511 may be a potent and selective agent for suppressing
      estrogen-dependent action without affecting serum levels of other steroid
      hormones.

PMID- 7577711
TI  - Inhibition of adrenal steroid metabolism by administration of 1
      aminobenzotriazole to guinea pigs.
AB  - Prior in vitro investigations demonstrated that the P450 suicide substrate, 1
      aminobenzotriazole (ABT), was a potent inhibitor of xenobiotic metabolism but had
      no effect on steroidogenic enzymes in the guinea pig adrenal cortex. Studies were
      done to determine if ABT administration of guinea pigs in vivo also selectively
      inhibited adrenal xenobiotic metabolism. At single doses of 25 or 50 mg/kg, ABT
      effected rapid decreases in spectrally detectable adrenal P450 concentrations.
      The higher dose caused approx. 75% decreases in microsomal and mitochondrial P450
      levels within 2 h. The decreases in P450 were sustained for 24 h but
      concentrations returned to control levels within 72 h. Accompanying the ABT
      induced decreases in adrenal P450 content were proportionately similar decreases
      in P450-mediated xenobiotic and steroid metabolism. Microsomal benzo(a)pyrene
      hydroxylase, benzphetamine N-demethylase, 17 alpha-hydroxylase and 21-hydroxylase
      activities were decreased to 20-25% of control values by the higher dose of ABT.
      Mitochondrial 11 beta-hydroxylase and cholesterol sidechain cleavage activities
      were similarly diminished by ABT treatment. Adrenal 3 beta-hydroxysteroid
      dehydrogenase activity, by contrast, was not affected by ABT, indicating
      specificity for P450-catalyzed reactions. The results demonstrate that ABT in
      vivo is a non-selective inhibitor of adrenal steroid- and xenobiotic-metabolizing
      P450 isozymes. The absence of ABT effects on steroid metabolism in vitro suggests
      that an extra-adrenal metabolite may mediate the in vivo inhibition of
      steroidogenesis.

PMID- 7577712
TI  - Contrasting effects of tamoxifen and ICI 182 780 on estrogen-induced calbindin-D
      9k gene expression in the uterus and in primary culture of myometrial cells.
AB  - Antiestrogens have a large range of tissue- and promoter-specific actions, many
      of which still remain unclear, particularly in the uterus. Thus, we have analyzed
      the effects of two antiestrogens, tamoxifen (TAM) and ICI 182 780 (ICI) on the
      uterine estrogen-responsive gene calbindin-D9k (CaBP9k), in the ovariectomized
      rat uterus, and in primary cultures of myometrial cells. In the ovariectomized
      rat uterus, estradiol (E2) or E2 plus TAM induced CaBP9k mRNA to the same levels
      in 6h. Rats given TAM alone had the same mRNA concentration, but maximal
      induction was obtained later, 12h after injection. ICI alone did not induce
      CaBP9k gene expression. Rats given E2 plus ICI had low uterine CaBP9k mRNA levels
      at 6-12h that became undetectable at 24h. Thus ICI has a full antagonistic effect
      on E2-induced CaBP9k gene. Estradiol receptor (ER) assays showed that TAM had a
      partial antagonist effect, while ICI had a full antagonist effect on the ER. We
      also analyzed the effect of TAM and ICI on CaBP9k gene expression in primary
      cultures of myometrial cells. The effects were similar to those observed in whole
      uterus. Thus, TAM has mixed effects, being an agonist for CaBP9k gene induction,
      and an antagonist for ER. ICI antagonizes the effects of E2 on the CaBP9k gene in
      myometrial cells and in the intact uterus, but in a way that does not involve a
      decrease in the cellular content of ER. Instead, it interferes with at least one
      of the events leading to transcriptional activation.

PMID- 7577713
TI  - The measurement of oestrone-3-glucuronide in urine by non-competitive idiometric
      assay.
AB  - We report a novel non-competitive idiometric assay for the measurement of
      oestrone-3-glucuronide (EG) in diluted urine. The method is based on the use of
      two types of anti-idiotypic antibody, the beta-type and alpha-type, that
      recognize different epitopes within the hypervariable region of the primary anti
      EG antibody (Ab1). The beta-type anti-idiotypic antibody is analyte sensitive and
      competes with the analyte for an epitope of the primary antibody at the binding
      site. On the other hand, the alpha-type is analyte insensitive, but does not bind
      the Ab1 in the presence of the beta-type due to epitope proximity. In the present
      format, reaction mixtures containing the europium labelled Ab1 are reacted
      sequentially with EG standards or diluted urine samples, with the beta-type anti
      idiotypic antibody and biotinylated alpha-type anti-idiotypic antibody on
      immobilized streptavidin coated microtiter plates. After 1 h incubation, the
      fluorescence of europium is measured by a time-resolved fluorescence and is
      proportional to the concentration of EG over a range of 0-10 nmol/l. The method
      demonstrates good sensitivity, precision and comparability with an alternative
      competitive fluorescent immunoassay. The idiometric assay for EG may be applied
      for the monitoring of ovarian function in women and is suitable for dipstick
      technology.

PMID- 7577714
TI  - Cytochrome P450 CYP27-catalyzed oxidation of C27-steroid into C27-acid.
AB  - Rabbit liver cytochrome P450 CYP27 has been previously shown to catalyze the
      complete conversion of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol into 3
      alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. This study compares
      some properties of the reactions involved, the 27-hydroxylation of 5 beta
      cholestane-3 alpha,7 alpha,12 alpha-triol and the further oxidation of 5 beta
      cholestane-3 alpha,7 alpha,12 alpha,27-tetrol. The Km was the same for the two
      substrates, whereas the Vmax was three times higher for 27-hydroxylation than for
      the oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol.
      Ketoconazole inhibited both reactions, whereas disulfiram did not. Carbon
      monoxide inhibited the 27-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha,12
      alpha-triol but not the further oxidation of 5 beta-cholestane-3 alpha,7 alpha,12
      alpha,27-tetrol. There was no difference in sensitivity to varying oxygen
      concentrations between the two reactions. The present study shows that CYP27 also
      converts, although less efficiently, 5 beta-cholestane-3 alpha,7 alpha-diol into
      3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid and cholesterol into 3 beta
      hydroxy-5-cholestanoic acid. The rate of oxidation of cholesterol into C27-acid
      was very low--less than 1% of that with the other C27-steroids.

PMID- 7577715
TI  - Serum and urinary markers of exogenous testosterone administration.
AB  - In an attempt to find optimal markers of exogenous testosterone (T)
      administration in male athletes, a number of compounds were measured in 11
      healthy men before and after 3, 6 and 9 months of weekly administration of 250 mg
      i.m. T enanthate and in age-matched untreated controls. The following variables
      were measured in serum: T, 17 alpha-hydroxyprogesterone (17-OHP), sex hormone
      binding globulin (SHBG), estradiol-17 beta, estrone (free + conjugated) and
      luteinizing hormone (LH). The following variables were measured in urine: T
      glucuronide (urinary T), epitestosterone glucuronide (urinary epiT), estrone
      (free + conjugated) and LH. Serum T, serum T/17-OHP ratio, serum T/LH ratio,
      serum T/SHBG ratio, serum and urinary estrogens, urinary T/creatinine-, T/epiT-
      and T/LH ratios increased whereas serum 17-OHP, SHBG and LH and urinary
      epiT/creatinine- and LH/creatinine-ratios decreased significantly during
      treatment. Levels above the upper reference limit were found in all subjects at
      3, 6 and 9 months for serum T/17-OHP and serum and urinary T/LH ratios and at 6
      months for the urinary T/epiT ratio. Levels below the lower reference limit were
      found in all subjects at 3, 6 and 9 months for serum LH and the urinary
      LH/creatinine ratio, at 3 months for the urinary epiT/creatinine ratio and at 9
      months for serum 17-OHP. No other variable showed abnormal values in all subjects
      at the same occasion. Despite significant changes during treatment, steroid
      concentrations as such are poor indicators of T doping. Serum and urinary LH
      levels, T/LH ratios and serum T/17-OHP ratios seem to be the most reliable
      markers of exogenous T administration in males.

PMID- 7577716
TI  - Urinary excretion of 6 beta-hydroxycortisol in women during treatment with
      different oral contraceptive formulations.
AB  - The measurement of the urinary excretion ratio of 6 beta-hydroxycortisol (6 beta
      OHC)/cortisol was used as a non-invasive method to investigate possible changes
      in the activity of drug-metabolizing enzymes in women receiving different oral
      contraceptive formulations for 1 up to 3 treatment cycles. The contraceptive
      preparations were either levonorgestrel, gestodene or cyproterone acetate, each
      in combination with ethinyl estradiol, or only the progestogens levonorgestrel or
      gestodene. There was either no or only a small decrease in the 6 beta
      OHC/cortisol ratio. Thus, only a minor inhibitory effect, if any, can be ascribed
      to the investigated contraceptive steroids in vivo. Previously observed
      differences between selected contraceptive steroids in vitro were not observed in
      the same way in vivo. This may be due either to the absence of a marked
      inhibitory activity in vivo or to the insufficient sensitivity of the marker 6
      beta-OHC/cortisol to detect these changes. Another possible reason may be the
      considerably higher drug concentrations used in the in vitro studies as compared
      to those present in the serum of women under oral contraceptive therapy.

PMID- 7577717
TI  - Analysis of the expression and the first exon of aromatase mRNA in monkey brain.
AB  - To elucidate the mechanism of the region-specific expression of the aromatase in
      the primate brain, we investigated the distribution and level of the total
      aromatase mRNA and the aromatase mRNA with the exon 1-f, which was reported to be
      the brain-specific exon 1 of the human aromatase gene, in male Japanese monkeys.
      Total RNAs extracted from the hypothalamus-preoptic area (HPOA), amygdala (AMY),
      cerebellum, hippocampus, brainstem, five regions of cerebral cortex and four
      peripheral tissues: liver, kidney, adipose tissue and testis were subjected to a
      semi-quantitative reverse transcription-polymerase chain reaction-Southern
      blotting (RT-PCR-SB) assay. The levels of the total aromatase mRNA was high in
      the HPOA, AMY and testis with a low level of message in the other regions. These
      results roughly paralleled the distribution of aromatase activity of the monkey
      brain previously reported. The level of the aromatase mRNA with the exon 1-f was
      high in the HPOA and AMY, and low in the other regions of the brain and the
      testis with an undetectable level of the messenger in the other peripheral
      tissues. Furthermore, the ratio of the aromatase mRNA with the exon 1-f to the
      total aromatase mRNA was different among various regions of the monkey brain, for
      example, the ratio in the AMY was distinctly higher than that in the HPOA. These
      results indicated that the level of the aromatase mRNA mainly regulated the level
      of aromatase protein and aromatase activity in a region-specific manner, and that
      the exon 1-f was used in most of the monkey brain regions. Moreover, the ratio of
      the aromatase mRNA with the exon 1-f to the total aromatase mRNA varied in the
      brain regions. It was implied that the aromatase mRNA using the other first exons
      was also expressed in the brain and was involved in the region-specific
      expression of the brain aromatase.

PMID- 7577719
TI  - Ubiquitous expression of the androgen receptor and testis-specific expression of
      the FSH receptor in the cynomolgus monkey (Macaca fascicularis) revealed by a
      ribonuclease protection assay.
AB  - Androgens are known to exert a variety of effects on an organism while follicle
      stimulating hormone (FSH) seems to act specifically on the gonads. To investigate
      whether these effects are reflected by the expression pattern of the androgen
      receptor (AR) or the FSH receptor (FSHR) we screened 38 different tissues and
      organs of one intact and one castrated male non-human primate (Macaca
      fascicularis). By means of a highly sensitive ribonuclease protection assay (RPA)
      we demonstrated AR mRNA expression in all tissues of the intact monkey
      investigated. Immunohistochemistry of selected organs from this monkey revealed a
      good correlation between AR mRNA and protein expression. In the castrated monkey,
      the overall AR mRNA expression was markedly lower compared with the intact
      monkey, although higher expression was present in the pituitary, thyroid and
      prostate glands. FSHR mRNA was only detected in testicular tissue. This study has
      revealed, for the first time, ubiquitious expression of the AR mRNA in a non
      human primate. The testis-specific expression of the FSHR highlights the
      importance of FSH for spermatogenesis with the testis being apparently the only
      target organ.

PMID- 7577718
TI  - Estrogen induces c-Ha-ras expression via activation of tyrosine kinase in uterine
      endometrial fibroblasts and cancer cells.
AB  - Endometrial fibroblasts derived from uterine endometrium as controls and
      endometrial cancer cells (Ishikawa and HHUA cells) were used to analyze the
      manner of induction of c-Ha-ras transcripts in endometrial cancers, some of which
      are estrogen-dependent in growth. Estrogen increased c-Ha-ras expression and
      tyrosine kinase (TK) activity in fibroblast and Ishikawa cells, but not in HHUA
      cells. Progesterone diminished c-Ha-ras expression and tyrosine kinase (TK)
      activity induced by estradiol in the fibroblasts, but not in Ishikawa cells,
      which persistently overexpressed c-Ha-ras. In these cells, epidermal growth
      factor (EGF) increased c-Ha-ras expression as did estradiol. Pretreatment with
      tyrphostin, an inhibitor of TK, abolished estrogen-inducible overexpression of c
      Ha-ras. The combination of both estradiol and EGF at maximum effective
      concentration exerted no additive or synergistic effect on induction of c-Ha-ras
      expression. In conclusion, persistent activation of TK might lead to
      overexpression of c-Ha-ras in some endometrial cancer cells under estrogen
      predominant milieu, which might be associated with the transformation or growth
      potential.

PMID- 7577720
TI  - The mitochondrion as a primary site of action of glucocorticoids: the interaction
      of the glucocorticoid receptor with mitochondrial DNA sequences showing partial
      similarity to the nuclear glucocorticoid responsive elements.
AB  - Six mitochondrial genome sequences, showing strong similarity to the
      glucocorticoid responsive element consensus sequence (GRE), four localized within
      the cytochrome c oxidase (COX) subunit I and II genes (GREs I-IV) and two within
      the D-loop region (GREs a and b) have been examined as binding sites of
      glucocorticoid receptor (GR) from rat liver cytosol. Purified GR from rat liver
      cytosol binds with high specificity to all potential mitochondrial GREs, as shown
      by filter retention and gel shift assays. Specific binding of protein(s), present
      in a mitochondrial extract from dexamethasone-induced mice, to all six putative
      mitochondrial GREs was also documented by the same methodology. Both purified GR
      and protein(s) from mitochondrial extract give the same band in the gel
      retardation assay. Using monospecific anti-glucocorticoid receptor polyclonal
      antibody (EP), a supershift of the gel retarded protein-DNA band was obtained.
      These results demonstrate that the mitochondrial genome sequences examined have
      characteristics of GREs, since they show the capacity to specifically bind the
      respective receptor protein. These findings support the hypothesis that the
      mitochondrial genome is a primary site of action of steroid and thyroid hormones
      (Sekeris C.E.: The mitochondrial genome: a possible primary site of action of
      steroid hormones, In vivo 4 (1990) 317-320).

PMID- 7577722
TI  - Androgens inhibit the proliferation of a variant of the human prostate cancer
      cell line LNCaP.
AB  - The paradoxical androgen response of R2, a subline of the human prostate cancer
      cell line LNCaP, is described here. Two androgens (DHT and R1881) decreased, in a
      dose-dependent manner, R2 cell proliferation and [3H]thymidine incorporation.
      These ligand and cell specific effects were accompanied by an increase in the
      metabolism of the vital dye MTT and in cell protein content. Both androgens
      increased the doubling time and the percentage of G0-G1 cells. No evidence of
      androgen-induced apoptosis was found. Cloning allowed the selection of two cell
      populations on the basis of the response to 10 nM of R1881. Long term culture of
      uncloned R2 cells with R1881 modified reversibly the pattern of androgen
      response. R2 was compared to the androgen-stimulated LNCaP-FGC subline to
      investigate the causes of their different androgen responsiveness. The androgen
      receptor (number, affinity for hormones and antihormones, sedimentation constant
      and molecular weight) and androgen receptor genes (exon size and exon 8 sequence)
      were found to be identical in the two sublines. EGF stimulated LNCaP-FGC but not
      R2. Both cells were slightly stimulated by basic FGF but were insensitive to IGF
      I and TGF beta 1. IN CONCLUSION: (1) androgens inhibit the proliferation of R2
      cells possibly by introducing a G0-G1 block; (2) this inhibition is incomplete
      because, at least in part, the R2 cell population is heterogeneous; (3) chronic
      androgen treatment induces reversible cell adaptation; and (4) there is no
      evidence that the loss of the classical stimulatory effect of androgen on cell
      proliferation and the gain of inhibitory effect are due to androgen receptor
      alteration or to a specific action of one of the four growth factors tested.

PMID- 7577721
TI  - Glucocorticoids enhance the cholesterol side-chain cleavage activity of ovine
      adrenocortical mitochondria.
AB  - We have shown previously that a chronic treatment with glucocorticoids enhances
      cAMP- or ACTH-induced steroidogenesis of cultured ovine adrenocortical cells.
      This effect appears to involve a greater amount of cholesterol in mitochondria.
      Hence, the present study aimed to define the role of glucocorticoids in
      cholesterol metabolism by these cells. 2-day-old cultures were exposed to
      different hormones or inhibitors (10(-6) M ACTH, 10(-5) M metyrapone) for 28-48
      h. At the end of the treatment period, the cells were stimulated for 2 h with 10(
      3) M 8Br-cAMP, in the presence of 10(-3) M aminoglutethimide (in order to load
      mitochondria with cholesterol). Mitochondria were then isolated and incubated
      without or with 100 microM cholesterol either in the presence or absence of 10(
      3) M CaCl2, or with 25 microM 22R-hydroxycholesterol. Mitochondria isolated from
      dexamethasone-treated cells produced consistently more pregnenolone than
      mitochondria from control cells, suggesting that at least part of the additional
      cholesterol present in these mitochondria was available for steroidogenesis.
      However, similar differences were obtained when mitochondria were incubated in
      the presence of exogenous cholesterol, both with or without calcium, or in the
      presence of 22R-hydroxycholesterol. Pregnenolone production under these latter
      conditions was much higher than when endogenous cholesterol was the only
      substrate. Conversely, metyrapone treatment of the cells resulted in lower
      production of pregnenolone from 22R-hydroxycholesterol by their mitochondria.
      Likewise ACTH treatment enhanced pregnenolone production by isolated mitochondria
      irrespective of the incubation conditions. These effects of dexamethasone and
      ACTH were not related to higher amounts of adrenodoxin, adrenodoxin reductase or
      cytochrome P450scc. These results indicate that exposure of ovine adrenocortical
      cells to glucocorticoids or ACTH enhances their steroidogenic potency not only by
      increasing the amount of cholesterol available for steroidogenesis but also by
      enhancing some step(s) involved in the transformation of cholesterol into
      pregnenolone.

PMID- 7577723
TI  - Lack of estrogenic potential of progesterone- or 19-nor-progesterone-derived
      progestins as opposed to testosterone or 19-nor-testosterone derivatives on
      endometrial Ishikawa cells.
AB  - Estrogen receptors of human endometrial cancer Ishikawa cells were found to be
      present in moderate amounts (160-200 fmol/mg protein), and to specifically bind
      moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM,
      when measured under equilibrium conditions. The binding specificity respected a
      decreasing order as follows: estradiol (E2: 100%) > 4-hydroxy-tamoxifen (4OHTAM:
      52.7%) > estriol (E3: 5.7%) > estrone (E1: 2.1%) > TAM (0.2%). The induction of
      alkaline phosphatase activity (APase) used as an estrogen-specific response,
      confirmed the intrinsic estrogenicity of progestins derived from 19-nor
      testosterone (19NT): norethindrone (NOR), norethynodrel and levonorgestrel, at
      concentrations ranging from 10(-8) to 10(-6) M. The effect of NOR was partially
      blocked by the antiestrogen 4OHTAM, which was also partially agonistic in this
      model, but neither by the antiprogestin mifepristone (RU486) nor by the aromatase
      inhibitor aminoglutethimide. A simulatory effect was also detected at 10(-7) or
      10(-6) M with ethindrone, the testosterone- (T) derived progestin homologous to
      NOR, and with both androgenic parent-compounds, i.e. T and 19NT themselves. In
      contrast, progesterone (P) derivatives like medroxyprogesterone acetate (MPA) and
      chlormadinone acetate (CMA) remained totally inactive, as well as 19-nor
      progesterone (19NP) itself or its progestagenic derivatives: ORG 2058 and
      nomegestrol acetate (NOM). Structure-activity relationships deduced from these
      studies suggest that it is not the absence of the 19-methyl group which can
      account for the estrogenic potential of the so-called "19-norprogestins", but
      rather their steroid structure derived from T in a broad sense (including the
      19NT derivatives), as opposed to the non-estrogenic therapeutic progestins
      derived from P like MPA or CMA, or from 19NP like NOM.

PMID- 7577724
TI  - Time-dependent effects of dexamethasone on glutamate binding, ornithine
      decarboxylase activity and polyamine levels in the transected spinal cord.
AB  - Evidence exists that the spinal cord is a glucocorticoid-responsive tissue, and
      glucocorticoids have beneficial effects in cases of spinal cord injury. Using
      sham-operated rats, spinal cord transected (TRX) rats, and TRX animals receiving
      dexamethasone (DEX) 5 min or 24 h post-lesion, we have examined the following GC
      sensitive parameters 6 h after DEX treatment: (1) binding of glutamate to NMDA
      sensitive receptors; (2) the activity of ornithine decarboxylase (ODC); and (3)
      levels of polyamines. We found that glutamate binding in the dorsal horn (Laminae
      1-2) and central canal were upregulated in TRX rats, whereas DEX had an
      additional stimulatory effect. 24 h post-lesion, glutamate binding was unmodified
      in TRX or TRX+DEX rats. ODC activity was increased 10-fold in rats killed on the
      day of transection but only 2-fold 24 h post-lesion. DEX reduced ODC activity on
      transection day but highly increased it when given 24 h after surgery. The
      content of the polyamines spermidine and spermine were unchanged after TRX or DEX
      treatment, in contrast to putrescine which increased in TRX rats and further
      increased in TRX+DEX rats when measured the day post-lesion. Thus, parallel
      increases in ODC and putrescine 1 day after the lesion, suggest that
      glucocorticoid effects on growth responses due to polyamines may develop at a
      late period. The changes of glutamate binding in the dorsal horn and central
      canal due to early glucocorticoid treatment, further suggest hormonal modulation
      of neurotransmission in sensitive areas of the deafferented spinal cord.

PMID- 7577725
TI  - Dexamethasone attenuates the estradiol-induced increase of IGF-I mRNA in the rat
      uterus.
AB  - In recent years growth factors, e.g. insulin-like growth factor-I (IGF-I),
      transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF),
      have been considered as mediators of estradiol-stimulated growth in the uterus.
      In the liver, dexamethasone (Dex) has been shown to inhibit the IGF-I mRNA
      increase induced by growth hormone (GH). In the present study the influence of
      Dex on estradiol-stimulated induction of uterine IGF-I mRNA was examined. The
      concentration of IGF-I mRNA in the uterus and liver was monitored, as well as the
      levels of ER mRNA and estrogen receptor (ER). Since it has been previously shown
      that the maximal induction of uterine IGF-I mRNA after estradiol (E2) stimulation
      occurs after 21-24 h, Dex was administered to ovariectomized (ovx) rats 3 h
      before an E2 injection and 24 h before sacrifice. There was a significant
      decrease in IGF-I mRNA in the Dex+E2 treated rats compared to the rats given E2
      only. In both groups an increase was seen compared to the level in the ovx
      control group. The uterine ER mRNA levels in E2 and Dex+E2 treated animals were
      significantly elevated compared to the ovx control. There were no significant
      changes in uterine ER content after hormone treatment compared to the level in
      ovx control rats. In the liver no effects on IGF-I mRNA were detected. Hepatic ER
      mRNA was significantly increased in the E2 treated group, compared to both the
      ovx control group and the animals that received Dex+E2. The hepatic ER level was
      also increased in the E2 treated group compared to the ovx control and the group
      which received Dex+E2. In conclusion, Dex does attenuate the estrogen-induced
      uterine IGF-I mRNA increase in ovx rats. In addition to this, Dex was found to
      inhibit the estrogen-induced increase in ER and ER mRNA in the liver of ovx rats.

PMID- 7577726
TI  - Reptilian (Chrysemys picta) hepatic progesterone receptors: relationship to
      plasma steroids and the vitellogenic cycle.
AB  - In non-mammals, estrogen-induced yolk precursors produced by the adult female
      liver are the main nutritional source for development. Evidence exists that
      progesterone exerts counter-regulatory effects on estrogen-induced
      vitellogenesis, and we have used the turtle model (Chrysemys picta) to study
      changes in hepatic progesterone receptor during the vitellogenic cycle. Using
      radioligand methods, we show that high and lower affinity binding sites are
      present in the cytosolic but not nuclear extracts. The lower affinity site is
      detectable at all times of the year; the high affinity site is mainly observed
      during non-vitellogenic periods and does not correlate with plasma estrogen. DNA
      cellulose chromatography shows that PR-A is present in spring, summer, and
      winter, and that PR-B is down-regulated except in animals which recently laid
      eggs. Western blots confirm the presence of PR in all months, but PR-A (88 kDa)
      is the dominant isoform. PR-B (125 kDa) is well correlated with the luteal phase,
      winter and fall. Immunocytochemical studies show that PR is nuclear in location,
      and nuclear heat shock protein 90 (hsp90) is present. Competitive binding studies
      of both sites reveal that progesterone is the most effective ligand for both,
      followed by pregnenolone, deoxycorticosterone, and R5020. RU 486 does not bind to
      the high affinity site but binds moderately well to the lower affinity site. This
      study suggests that progesterone receptor isoforms are differentially expressed
      and may be involved as transcriptional regulators of hepatic function outside the
      periods of active vitellogenesis in the turtle.

PMID- 7577728
TI  - Microbiological assessment of dentin stained with a caries detector dye.
AB  - The purpose of this study was to assess microbiologically the efficacy of 1% acid
      red in propylene glycol dye to stain carious dentin. Thirty teeth with primary
      carious lesions involving dentin were chosen. Cavity preparation using the
      conventional visual and tactile criteria was done and the dye was applied to the
      prepared cavity. Dentin samples were collected, from carious dentin prior to
      cavity preparation, dye stained areas and unstained areas. The total colony
      forming units (CFU) in each sample were then assessed microbiologically. The
      results showed a highly significant difference in the total colony forming units
      in dye stained and dye unstained dentin samples. The 1% acid red dye in propylene
      glycol dye was found to be effective as an adjunctive aid in the diagnosis of
      carious dentin.

PMID- 7577727
TI  - Acidulated phosphate fluoride treatment and formation of caries-like lesions in
      enamel: effect of application time.
AB  - The aim of this study was to evaluate the effect of acidulated phosphate fluoride
      (APF) application time (1 and 4 minutes) on caries-like lesion formation in
      enamel. Following a fluoride-free prophylaxis, the specimens (10 extracted human
      molars) were divided into tooth quarters and assigned to treatment groups: 1)
      Distobuccal and Distolingual Quarters--1 minute APF; 2) Mesiobuccal and
      Mesiolingual Quarters--4 minute APF. Acid-resistant varnish was applied to the
      tooth quarters, leaving sound enamel windows exposed on buccal and lingual
      surfaces. Following treatment, the APF gel (Oral-B Minute Gel) was removed by air
      water spray rinsing, followed by a 24-hour water rinse. Sound enamel windows
      protected from APF treatment by acid-resistant varnish were created adjacent to
      APF-treated sound enamel windows and served as paired controls. Lesions were
      created in APF-treated and paired control sound enamel windows with an acidified
      gel. After lesion formation, sections were obtained and imbibed with water for
      polarized light study. Body of the lesion depths were measured and compared
      statistically. Mean body of the lesion depths were: 186 +/- 28 microns for
      control lesions, 117 +/- 12 microns for APF-1min; and 111 +/- 14 microns for APF
      4min. Significant differences (p < 0.05) were found between paired control and
      APF groups. No difference (p > 0.05) was found between APF-1min and APF-4min
      groups. APF treatment prior to lesion formation resulted in a significant
      reduction in lesion depth, regardless of whether a 1 or 4 minute APF treatment
      period was used. The 1 minute APF treatment provided the same degree of caries
      protection as the longer treatment period.

PMID- 7577729
TI  - Slime production by coagulase-negative staphylococci in the infected pulps.
AB  - In this study; slime factor which is produced by coagulase negative Staphylococci
      was investigated in infected pulps of 145 primary and permanent teeth.
      Staphylococci were isolated in 27% of the cultures and all of the isolated
      Staphylococci were coagulase negative (CNS) in permanent teeth whereas 75% of
      isolated Staphylococci were coagulase negative in primary teeth. Slime production
      rate was the same for both groups and 22% of CNS were found slime positive. It is
      thought that slime production is important not only in endodontic microbiology,
      but also in other fields of dentistry for the explanation of the pathogenesis of
      infection.

PMID- 7577732
TI  - Posterior bite raising effects on a primary anterior crossbite case.
AB  - Stainless steel crowns were cemented on the mandibular primary molars to make
      bite raising for an anterior reversed bite case. Chewing force and MKG were
      recorded before and after bite raising. Data from MKG revealed that co-ordination
      pattern of muscle activities after bite raising became higher in masseter muscles
      than those before anterior reversed bite was corrected easily without any incisal
      interferences by using this treatment method.

PMID- 7577730
TI  - Laser vs visible-light cured composite resin: an in vitro shear bond study.
AB  - This study was conducted to compare the shear bond strength of composite resin to
      enamel surface, etched by 37% phosphoric acid for 30 and 60 sec respectively,
      after achieving the polymerization of composite resin by a conventional visible
      light and argon laser curing system in permanent and primary teeth. Results
      demonstrated higher shear bond strength with laser polymerization exposed for 10
      sec compared to conventional visible-light exposed for 40 sec polymerization.
      This increased bond strength was statistically significant in primary teeth,
      whereas, in permanent teeth it was insignificant. The different etching times
      used in the present study showed no statistically significant difference in bond
      strengths for either of the curing systems.

PMID- 7577731
TI  - Retention of orthodontic bands with three different cements.
AB  - In 1878, zinc phosphate cement was introduced as a dental material and used to
      cement orthodontic bands. The prevalence of enamel decalcification beneath
      orthodontic bands has indicated the need for a fluoride-releasing orthodontic
      luting cement. The purpose of this study was to compare the retentive bond
      strengths of orthodontic bands cemented individually with zinc polycarboxylate,
      glass ionomer and zinc phosphate cement adhesives. Forty-eight extracted human
      molar teeth were embedded in resin blocks and each was randomly assigned to one
      of the three cement groups. Adapted bands were cemented by using hand pressure
      and a band seater. The cemented teeth were then put in synthetic saliva at 37
      degrees C for twenty-four hours. The force required to fracture the cement bond
      was used as a measure of cement retention. Using an Instron universal testing
      machine, a tensile load was applied to each cemented band. The Kruskal-Wallis one
      way analysis of variance test revealed no significant differences (p > 0.05)
      among the retentive strengths of the three cements. Both the zinc polycarboxylate
      and the glass ionomer cements tested were found to be suitable as orthodontic
      luting agents. In addition, the ability to bond to enamel and stainless steel and
      to leach fluoride make the glass ionomer cement an ideal orthodontic cement.

PMID- 7577733
TI  - CT display of multiple dentigerous cysts of the mandible: a case report.
AB  - Computerized tomographic (CT) display of a case with multiple dentigerous cysts
      in the mandible is presented and benefits of the CT in such cases are discussed.
      CT images provides 3 dimensional accurate details of the cystic lesions without
      any distortion and superposition. It shows the exact size, location and possible
      origin of the cysts as well as the extent of the bone destruction. It is
      considered that CT could be used as a guide in presurgical evaluation of the
      complex cystic lesions of the jaws.

PMID- 7577734
TI  - Peripheral adenomatoid odontogenic tumor: birth of a term.
AB  - The terminology of adenomatoid odontogenic tumor had been reviewed and the
      different names for this lesion used over the course of time have been listed. A
      case of peripheral adenomatoid odontogenic tumor which occurred on the gingiva of
      the right maxillary central incisor of a 4-year-old girl is reported.

PMID- 7577735
TI  - XXXXY syndrome: report of case.
AB  - XXXXY Syndrome is a rare disorder characterized by multiple anomalies including
      growth deficiency, hypogenitalism, craniofacial anomalies and dental problems.
      Some experts feel this syndrome is a derivative of Klinefelter's Syndrome and may
      be associated with advanced maternal age. The case of a seven year old male with
      XXXXY syndrome is presented. A dental rehabilitation involving outpatient surgery
      is described.

PMID- 7577736
TI  - Actisite (tetracycline hydrochloride periodontal fiber) not a product for the
      pediatric dentist.

PMID- 7577738
TI  - Orthodontic goniometry: detection and measurement of apical movement: Part 1.
AB  - The possibility of apical expansion has been a matter of debate for a long time
      in orthodontics. Measure of expansion is easily obtained at the level of the
      crowns, but is coronal expansion a significant measure for apical expansion? This
      question received an answer as early as 1948 with the practical use of a method,
      "orthodontic goniometry" created by M. Chateau measuring the angular changes of
      incline of teeth (gonio = angle; metry = measurement).

PMID- 7577737
TI  - Occlusal plane: a clinical evaluation.
AB  - The observation of the evolutionary characteristics of Hominid, of the
      ontogenesis of the occlusal biologic system and of the architectural influence of
      the occlusal field on the craniofacial morphology brings the evidence of the need
      for a clinical evaluation of the occlusal plane as an alternative approach to
      diagnosis in each treatment of the child, adolescent, adult or elder person. The
      purpose of this paper is to specify some indicators on the occlusal plane with
      regards to its inclination, length, continuity that facilitate the differential
      diagnosis especially during development, including those related to orofacial
      pain and TMJ disturbances.

PMID- 7577739
TI  - Orthodontic goniometry: results: Part 2.
AB  - This article provides the essential from Dr. Chateau's earlier research (1948)
      published in Rev. Mensuelle Suisse d'Odontologie. This research revealed the
      various steps of adaptation and stabilization after expansion through the help of
      Orthodontic Goniometry.

PMID- 7577740
TI  - Intraoperative and postoperative physiological monitoring practices by pediatric
      dentists.
AB  - The medical and dental literature has described successful sedations and those
      which have resulted in injury and death. Physiologic monitoring of patients is
      essential in assuring the success and safety of sedations in the dental office.
      The purpose of this study was to investigate the utilization and preferences of
      various physiologic monitoring methods and utilization of dentist
      anesthesiologists by pediatric dentists during sedations. Pediatric dentists in
      California were surveyed [n = 261] regarding monitoring methods in five different
      case scenarios. The most frequently utilized methods were clinical observation,
      pulse oximeter, and precordial stethoscope. Eighty seven percent of the pediatric
      dentists who use sedation do so without the involvement of a dentist
      anesthesiologist. Eighteen percent of pediatric dentists do not use any sedative
      agents in their practice. In the five case scenarios described in the survey,
      clinical observation was the most frequently utilized monitoring method during
      intra- and postoperative periods, followed by the pulse oximeter and precordial
      stethoscope. Intra- and postoperative monitoring varied with the complexity of
      the case scenario and most respondents monitored continuously. The trends
      observed from this study indicate that recent graduates use more sedative agents
      and find the pulse oximeter to be useful for physiologic monitoring during
      sedation.

PMID- 7577741
TI  - Early loss of pit and fissure sealant: a clinical and SEM study.
AB  - The rate of early loss of preventive resin restoration and single application of
      pit and fissure sealant was determined by a clinical survey. The rate of partial
      and complete sealant loss on the observed surfaces was 14.4% (43/299) at the 3
      month recall, with a further loss of 7.0% (12/171) between the 3- and 6-month
      recalls. Typically, a complete loss of sealant was observed on maxillary molars
      and on the buccal surface of mandibular molars, while partial loss caused on the
      occlusal surface of mandibular molars. Scanning electron microscopic observation
      of in vivo tooth replicas revealed partial gap formations and small fractures of
      sealant indicating failure or degradation of adhesion. The presence of unetched
      areas after routine cleaning and acid etching, especially in and around pits and
      fissures could be a major cause of early sealant loss.

PMID- 7577742
TI  - Assessment and significance of diploid-range epithelial populations in DNA
      aneuploid breast carcinomas using multi-parametric flow cytometry.
AB  - A 2-color (PI, cytokeratin--FITC) multi-parametric analysis of intact cells was
      used to reveal diploid-range epithelial populations by flow cytometry in 108
      consecutive DNA aneuploid breast carcinomas. Thirty-eight tumors (35%) contained
      a significant diploid range epithelial population, defined as cytokeratin
      positive cells having a DNA content indistinguishable from that of endogenous
      lymphocytes and comprising at least 20% of all cytokeratin-positive cells. An
      additional 23 cases (21%) contained a minor diploid range epithelial population
      having a normal DNA content and comprising only 5-20% of all cytokeratin-positive
      cells. Multiple DNA aneuploid stemlines were present in 24 cases (22%). Diploid
      range populations were more frequent (91%) in tetraploid cases than in
      hyperdiploid (32%), hypodiploid (17%) or hypertetraploid cases (20%). The
      presence of diploid epithelial populations and/or multiple aneuploid stemlines
      correlated with histologic parameters, including an extensive intraductal
      component (unimodal--4% vs. multi-modal--57%, P = 0.001), heterogeneous
      differentiation (unimodal--0% vs. multi-modal--52%, P = 0.001), and multi-focal
      growth with residual interspersed benign tissue (unimodal--8% vs. multimodal-
      57%, P = 0.01). These data show that diploid-range epithelial cells are frequent
      in aneuploid breast carcinomas analyzed by flow cytometry. In some tumors, these
      populations undoubtedly reflect the presence of residual benign epithelium. The
      numerical dominance of other histograms by near-diploid measurements suggests the
      presence of diploid-range neoplastic stemlines which would be 'hidden' by
      contaminating host-derived cells in single parameter DNA histograms. Finally, the
      correlation of DNA content heterogeneity with distinctive histologic patterns of
      breast neoplasia implies that co-existing stemlines may have biological
      significance in the progression of some tumors.

PMID- 7577743
TI  - Morphometry of experimental lung contusion: an improved quantitative method.
AB  - Alterations of lung tissue following pulmonary contusion are mainly assessed
      qualitatively. Quantitative examinations were limited up to now, to
      investigations in X-ray and computer tomography images, since morphometry of
      contused and normal biotic lung tissues seemed to be methodologically unfeasible.
      In order to overcome this shortcoming, the lungs of pigs were examined after
      unilateral lung contusion. In semithin sections, the thickness distribution of
      the interstitium and the volume distribution of the alveolar cavities were
      studied. Using an image analysis system a sequence of detection, erosion and
      skeletonisation steps were used to recognize the septal tissue correctly. The
      percent distributions were calculated from chord measurements after a sequence of
      erosion steps. It turned out that this technically simple procedure enabled
      highly reliable and valid results to be obtained, concerning the morphometric
      analysis of the alterations in the contused, as well as in the non-injured lungs.

PMID- 7577745
TI  - Abnormalities of esterase and glycogen in developing macrophages in non-Hodgkin's
      lymphoma: a quantitative cytochemical study.
AB  - Integrating microdensitometry has been used to quantitate changes in 4
      cytoplasmic enzymes (NADH dehydrogenase, succinate dehydrogenase, acid
      phosphatase and alpha-naphthyl butyrate esterase), DNA, RNA and glycogen in
      developing macrophages from 17 patients with non-Hodgkin's lymphoma and 19 normal
      subjects. Cytochemical measurements were made at intervals over 6 days of
      suspension culture; over 16 000 individual cells were examined in total and the
      results subjected to analysis of variance. While the levels of enzymes and RNA of
      both groups showed increases over the period of culture, the levels of alpha
      naphthyl butyrate esterase in the patients' cells were consistently lower than
      the corresponding values for the normal cells and glycogen levels were higher,
      these differences satisfying the pre-determined requirements for statistical
      significance. It is concluded that (a) maturational changes take place in
      cytochemical constituents of developing macrophages of non-Hodgkin's lymphoma (b)
      there are disturbances affecting the amounts of the specific enzyme alpha
      naphthyl butyrate esterase and glycogen (c) these abnormalities may be part of a
      compromise of host defense mechanisms by the disease, although a pre-existing
      defect in esterase increasing the susceptibility to malignancy is another
      possibility, and (d) the methods used may be of value in future investigations of
      the cause of the disturbances and their correction.

PMID- 7577744
TI  - DNA content in colorectal carcinoma: a flow cytometric study of the epithelial
      fraction.
AB  - The aim of this study was to estimate the proliferative activity of the
      epithelial fraction in human colorectal carcinomas. Cell suspensions from 27
      human colorectal carcinomas were simultaneously selected for epithelial cells and
      analyzed for DNA content. The staining procedure we employed, after dispersing
      the tumour sample into a single-cell suspension, included propidium iodide and a
      monoclonal antibody to the intermediate filament cytokeratin specific for
      secretory epithelia of normal human tissue and cells of epithelial origin in
      adenocarcinomas. This technique made it possible to distinguish the epithelial
      cell population from non-epithelial cells in the tumour. Flow cytometry was used
      for DNA analysis and the results obtained after epithelial selection were
      compared with conventional DNA analysis of crude tumour tissue. No difference in
      S-phase values of diploid and aneuploid cytokeratin positive cells were seen,
      whereas analysis of crude tumour cell suspensions showed lower S-phase values in
      diploid tumours compared to aneuploid ones. When cytokeratin-positive cells in
      the tumour were selected, we found presence of diploid tumour cells in almost all
      aneuploid tumours.

PMID- 7577746
TI  - Primary gastric lymphomas (MALTomas): a nuclear image analysis comparison with
      lymph node monocytoid B-cells and marginal zones of spleen and Peyer's patches.
AB  - Centrocyte-like cells of marginal zones of follicles of gastrointestinal lymphoid
      tissue, which have their analogous in marginal zone of splenic white pulp and in
      lymph node monocytoid B-lymphocytes, are thought to be the normal counterpart of
      lymphomas of MALT (MALTomas). However, the cell population of MALTomas is often
      polymorphic and also contains cells morphologically different from centrocytes.
      Since conventional morphologic analysis may not be accurate enough and the
      phenotype may change in different stages of B-cell lineage, the marginal zone of
      Peyer's patches (PMZ) and splenic white pulp (SMZ), the lymph node monocytoid B
      lymphocytes (ML), 3 nodal monocytoid B-cell lymphomas (L) and 16 gastric MALTomas
      (M) were studied by means of automated nuclear image analysis for area,
      irregularity, and chromatin texture assessment. Immunophenotyping on paraffin
      sections and polymerase chain reaction (PCR) for detecting monoclonality and t(14
      18) chromosome breakpoints at DNA levels, on paraffin section extractions, were
      also done. In 14 MALTomas, clonal Ig heavy chain rearrangement was detected and
      in none of these were found t(14-18) chromosome breakpoints. The nuclei of the
      control group (PMZ, SMZ and ML) showed the same morphologic characteristics, ie.
      size, irregularity, chromatin texture. MALTomas and nodal lymphomas were
      distributed into 3 clusters: (1) with larger nuclei, light chromatin (euchromatin
      richer) (5 MALTomas, 2 nodal lymphomas together with the control group); (2)
      nuclei with the same area size, but darker (eterochromatin-richer) (6 MALTomas
      and 1 nodal lymphoma); (3) with smaller and darker nuclei (5 MALTomas). Chromatin
      textural differences were maintained in the same nuclear size class in the 3
      clusters. Only a few MALTomas had nuclear features not significantly different
      from controls, inter-case and intra-case variability being evident.

PMID- 7577747
TI  - Intratumoral regional heterogeneity of DNA ploidy patterns in colorectal
      carcinomas.
AB  - There is no agreement on the evaluation of intratumoral DNA ploidy heterogeneity,
      and its clinical significance remains controversial. We categorized intratumoral
      ploidy heterogeneity in an effort to avoid confusion and misunderstanding among
      investigators. We classified the heterogeneity into 3 major types (Types A, B and
      C) and a combined type (Type D), based on the intratumoral distribution profiles
      of DNA aneuploid lines identified by flow cytometry in 52 cases of colorectal
      cancer with intratumoral DNA ploidy heterogeneity selected from a consecutive
      series. Every carcinoma examined in this study fell into one of the 4 categories:
      Twenty-six tumors (50%) were classified as Type A, 6 (11%) as Type B, 2 (3%) as
      Type C, and 18 (36%) as Type D. We discussed the mechanisms of DNA ploidy
      heterogeneity evolution within a tumor, and also proposed a pathway to these
      types of DNA ploidy heterogeneity as an aid to understanding the relationship
      between tumor progression and DNA ploidy changes.

PMID- 7577748
TI  - Immunohistochemical analysis of dendritic/Langerhans cells in thyroid carcinomas.
AB  - Recent immunohistochemical investigations of thyroid carcinomas have revealed
      that dense infiltration by dendritic cells (DCs) is correlated with a favorable
      prognosis. The present study was done to clarify the frequency and
      characteristics of DC infiltration in thyroid carcinomas, and also cytokines
      associated with DC maturation and migration. Compared with follicular carcinomas,
      papillary carcinomas contained significantly higher numbers of DCs, interleukin
      (IL)-1 alpha- and tumor necrosis factor (TNF)-alpha-positive cells, and cells
      positive for two TNF-alpha receptors (p60 and p80). The centers of cancer nodules
      had large numbers of CD1a- and CD1c-positive DCs suggesting that they were
      Langerhans cells, whereas the periphery of cancer nodules and inflamed
      surrounding thyroid tissues had numerous CD1b-, L-M2- and X-12-positive DCs
      suggesting that they were interdigitating cells, as well as many CD1a- and CD1c
      positive DCs. Neoplastic cells of papillary carcinomas were more frequently
      reactive with antibodies against IL-1 alpha and TNF-alpha than those of
      follicular carcinomas, and a good correlation between their immunoreactivity and
      the frequency of DCs was found. These data suggest that cytokines such as IL-1
      alpha and TNF-alpha released from carcinoma cells and cells in the cancer stroma
      may regulate the infiltration and maturation of dendritic/Langerhans cells, and
      that this process may be better preserved in papillary than in follicular
      carcinomas.

PMID- 7577749
TI  - A simple and rapid flow cytometric method to measure lymphocyte activation in
      HIV+ subjects. Diminished response to pokeweed mitogen in early disease.
AB  - It was our objective to investigate the effect of asymptomatic infection with HIV
      on the expression of lymphocyte activation markers after stimulation with
      mitogens. Whole blood cultures were made of HIV+ and HIV- subjects (29
      asymptomatic HIV-1-infected subjects and 33 apparently healthy normal
      volunteers). At various times after stimulation with concanavalin A (Con A), anti
      CD3 and pokeweed mitogen (PWM), the expression of activation markers (CD25 and
      HLA-DR) and the blastogenesis were quantified by flow cytometry. The flow
      cytometric quantification of the expression of activation markers and
      blastogenesis in whole blood cultures provided an easy and safe alternative to
      thymidine incorporation to assess lymphocyte responses in HIV+ subjects.
      Activation showed a tendency to be lower in the HIV+ subjects with all three
      stimulants. This difference with HIV- subjects was statistically significant only
      for stimulation with PWM after 4 days. Further investigations should be
      undertaken to show whether this functional impairment is related to disease
      progression and whether it can be influenced by effective therapy.

PMID- 7577750
TI  - Increase of precision and accuracy of DNA cytometry by correcting diffraction and
      glare errors.
AB  - In recent TV-based image cytometers considerable disproportionalities exist
      between the IOD values of reference cells, as well as diploid, tetraploid, and
      octoploid analysis cells compared with their theoretical IOD ratios. An important
      source of these deviations is the limited spatial resolution of the microscopic
      objectives, based on the effects of diffraction. Compared to these influences the
      glare is less important. A correcting method is given for reducing both effects
      on the DNA measurements, which considers a narrow region along the nuclear
      contour to be optically disturbed. The correction of this mean optical density
      (MOD)- and size-dependent geometric resolution error is applicable to any cell
      type. The method was tested on 25 rat liver imprints and 29 fine needle aspirates
      from breast cancers. The resulting stemline ratios are close to the theoretical
      ones. A further improvement was then reached by a glare correction. The slide-by
      slide variations of stemline ratios, remaining after the corrections, were
      considered in a test statistic for defining the aneuploidy of a given stemline.
      Statistically based clear-cut decision rules were obtained for DNA histogram
      interpretation.

PMID- 7577751
TI  - Fluorescence image analysis of the MCF-7 cycle related changes in chromatin
      texture. Differences between AT- and GC-rich chromatin.
AB  - This paper reports on quantitative in situ changes in chromatin structure that
      occur throughout the cell cycle of the human breast cancer epithelial cell line,
      MCF-7. Texture parameters were measured by image cytometry on nuclei stained by
      DNA specific fluorochromes. These parameters calculated from the co-occurrence
      and run length matrices of grey level images were previously shown to be related
      to condensation, organization and distribution of DNA. In some experiments, cells
      were triple stained for DNA/Ki-67/PCNA, and compartmentalization in the cycle was
      ascertained from the Ki-67/PCNA pattern expression. In these experiments, Hoechst
      dye was used to stain DNA. Chromatin of cells traversing G1 phase progressively
      decondensed and became homogeneously distributed. In addition, these G1 cells had
      more condensed chromatin than cells in G0 phase (as determined by Ki-67 negative
      staining). During the S and G2 phases, chromatin condensation took place and an
      increasing reticulated organization was quantified. Similar profile of changes in
      chromatin texture was found in experiments done with cells double stained by AT
      specific Hoechst dye and the GC-specific mithramycin dye. GC-rich chromatin
      texture-associated parameters greatly varied comparing to those of AT-rich
      chromatin during the G0/G1 phase as well as in the first mid-S phase. Conversely,
      variation of the AT-associated parameters was much greater in the second half of
      S phase as compared to the GC-associated parameters that barely varied during
      this period. This study well establishes the correlation between in situ
      chromatin texture and proliferation state because the latter is assessed by
      proliferation-associated antigens. Moreover, changes in chromatin texture are
      independently ascribed to the AT- and GC-rich regions suggesting that these 2
      types of chromatin are involved to different extents in transcriptional and
      replicational tasks.

PMID- 7577752
TI  - How thick is your section? The influence of section thickness on DNA-cytometry on
      histological sections.
AB  - The exact determination of the thickness of paraffin sections used for DNA
      cytometry on histological slides is an inevitable prerequisite to obtain reliable
      and reproducible results. Although section thickness can be measured with great
      precision and accuracy using highly specialized equipment (e.g. confocal laser
      microscope, microinterferometer), their cost restricts availability for many
      laboratories. This paper describes a simple method to determine the actual
      thickness of routinely processed paraffin sections used for DNA cytometry
      employing standard laboratory equipment. To achieve this goal the given section
      is divided into two parts. One part is used for DNA quantitation whereas the
      other is re-embedded and resectioned orthogonally through its original thickness.
      The thickness of the re-embedded section can now easily be determined with any
      standard length measurement device available in light microscopy. Recalculation
      of the genuine DNA-content out of the measured fractioned nuclei with commercial
      software based on the section thickness determined by this method generated
      histograms with a 2c equivalent peak, whereas correction based on the microtome
      settings resulted in significant deviations as demonstrated on rat liver tissue.

PMID- 7577753
TI  - Re-evaluating the AgNOR staining response in Triton X-100-treated liver cells by
      image analysis.
AB  - The response of liver cell nuclei to a variant of the AgNOR method, which
      includes a treatment with Triton X-100 prior to staining assumed to improve the
      quality of the AgNOR-positive images, was compared to that of the usual method by
      image analysis procedures. The objective was to determine whether Triton X-100
      removes proteins from the nuclei to the point of affecting the AgNOR response.
      Statistically significant differences were not found in comparisons of a nuclear
      area/AgNOR-stained area ratio nor in the number of AgNOR-positive
      dots/aggregates. It was thus assumed that the Triton X-100 treatment did not
      remove nuclear proteins likely to affect the AgNOR response, though it induced a
      cleaner background and, consequently, a clearer contrast between the stained
      areas and the background.

PMID- 7577754
TI  - Optimization of immunohistochemical staining of proliferating cells in paraffin
      sections of breast carcinoma using antibodies to proliferating cell nuclear
      antigen and the Ki-67 antigen.
AB  - Antibodies to proliferating cell nuclear antigen (PCNA) and the MIB-1 antibody to
      the Ki-67 antigen were titrated to optimize identification of proliferating cells
      in formalin-fixed paraffin-embedded tissue from a series of 40 human breast
      carcinomas. Cell culture studies have previously demonstrated that immunostaining
      for both PCNA and the Ki-67 antigen produces strong granular nuclear staining
      during S phase. PC10, other anti-PCNA antibodies (PC2, PC5, PC8 and 19F4) and MIB
      1 were used at the minimum dilution which allowed a clear distinction between
      cells with strong and weak staining. With the anti-PCNA antibodies, nickel-cobalt
      enhancement of the reaction product was found to augment the granular nature of
      nuclear staining, corresponding more closely to patterns observed in cell culture
      studies. No enhancement was found to be necessary for MIB-1. The labelling
      indices of all these antibodies were compared with S phase fraction (SPF)
      obtained by DNA flow cytometry in the same cases. The PC10 labelling indices
      which included only strongly stained cells correlated well with SPF, but counting
      all strongly and weakly stained cells showed a poor correlation. With MIB-1,
      counting strongly stained as well as all stained cells produced labelling indices
      which correlated well with SPF, the former tending to be lower and the latter
      higher. None of the other anti-PCNA antibodies showed any advantage in
      application over PC10. Thus, PC10 and MIB-1, applied with care, can be correlated
      with S phase fraction in paraffin processed tissue sections of breast carcinomas.

PMID- 7577756
TI  - False positive cervical smears: a cytometric and histological study.
AB  - The evidence of exfoliative cytology of the cervix uteri depends on various
      factors. The rate of false positive cervical smears is on average 8.8%. We have
      reviewed 170 false positive routinely Papanicolaou-stained cervical smears and
      the corresponding histological specimens. The aim was to look for non-neoplasic
      changes explaining the cytological over-interpretation. In addition, nuclear
      Feulgen-DNA measurements of the smears were made to look for changes in DNA
      pattern. In 50% of all cases, a cause was found for the false positive
      cytological diagnosis by means of histological reexamination: non-neoplastic
      nuclear and cellular polymorphia, severe purulent-erosive inflammation, a higher
      reclassification or a positive presurgical biopsy. In 51.9% of these cases, there
      were signs of an infection with human papilloma virus (HPV). In cases without
      histological explanation of the cytological findings, DNA measurements were made
      on the suspicious cells. By means of single cell algorithm (5c/9c exceeding
      events), a general rate of 62.7% of aneuploid specimens was detected. The number
      of aneuploid single cells ranged between 5 and 63 per slide. Of these cases,
      23.1% showed signs of HPV infection. As a result of the study, the number of real
      'false positive' cytological diagnoses decreased from 170 to 97 as a result of
      histological reexamination and DNA measurement. In doubtful cases, DNA
      measurement of suspicious smears should be made.

PMID- 7577755
TI  - Expert consultation by use of telepathology--the Heidelberg experiences.
AB  - The benefits and constraint using visual telecommunication in pathology
      (telepathology) are described based upon the experiences of the authors for more
      than 4 years. The experiences include first trials in visual telecommunication to
      analyze image quality, transfer rates, handling of commercially available
      equipment, and need for routinely diagnostic work followed by routinely expert
      consultations in frozen sections. A quality control study on diagnostic
      reliability of bronchial carcinomas was performed later, and the diagnosticly
      different cases were reclassified by a panel of pathologists using visual
      telecommunication. The latest experiences are based upon routinely expert
      consultations in morphologically difficult cases by ISDN-based telecommunication.
      As a result, image quality and transfer rates are sufficient to permit efficient
      expert contribution to diagnostically difficult cases in 30-50% of transmitted
      cases in both common telephone lines and ISDN connections. No influence of
      various staining procedures, immunohistology, or in situ hybridization on image
      quality or transfer rates were observed. The area of transmitted images is still
      too small, and the reliability of ISDN lines is still not sufficient for remote
      control service in Germany. The handling of commercially available equipment
      needs to be improved; however, as a general result, telepathology will probably
      improve the diagnostic quality and access in histopathology within the coming
      years.

PMID- 7577757
TI  - A simple and accurate method for 3-D measurements in microcorrosion casts
      illustrated with tumour vascularization.
AB  - Microvascular corrosion casting is an established method to investigate vascular
      patterns of nearly all organs. Trying to evaluate these specimens quantitatively
      using native scanning electron microscope (SEM) pictures always implied a big
      error, because the information of depth cannot be taken into account. However,
      SEM stereo pairs allow for exact measurements. Tumour microcorrosion casts were
      used to demonstrate the feasibility of this 3-D quantification method. The
      information of depth was calculated for each measuring point using the parallax.
      From the resulting coordinates the intervascular distances, the interbranching
      distances as well as the interbranching angles were determined. We found
      significant differences between all investigated tumours. Reproducibility tests
      and tests for the greatest error possibilities resulted in a maximum deviation of
      2.5% to be expected. Consequently this method is suitable for all application
      ranges of microvascular corrosion casting as a quantitative determination method.

PMID- 7577758
TI  - Family violence and police utilization.
AB  - This study examines the utilization of police service for domestic incidents.
      Contrary to the popular image of serious violence perpetrated upon a spouse, the
      data show that most calls involve less serious incidents that are almost as
      likely to involve cohabitants as married couples. This finding assumes
      significance because of the small proportion of the cohabiting population to the
      married population. Other types of relationships that generate calls to the
      police include, although to a lesser extent, parent-child, boyfriend-girlfriend,
      and siblings. Explanation for these findings focuses on relationship issues and
      provides implications for service utilization.

PMID- 7577759
TI  - Relationship between alcohol consumption and victim behaviors immediately
      preceding sexual aggression by an acquaintance.
AB  - A survey of 942 female college students (85% return rate) from four New England
      colleges and universities indicated that 25% had been victims of sexual
      aggression by an acquaintance since the age of 16. Fifty-five percent of the
      victims indicated they were at least somewhat drunk at the time of the sexual
      aggression. Those who felt they were at least somewhat drunk reported engaging in
      higher levels of consensual sexual activity with the aggressor immediately prior
      to the assault and reported lower levels of resistance than those who were not at
      all drunk. The implications these results may have for increased vulnerability to
      sexual aggression are discussed.

PMID- 7577760
TI  - Culture and domestic violence: the ecology of abused Latinas.
AB  - This study examined the predictors of domestic violence within a sample of 60
      immigrant Latinas, of whom 30 had sought assistance for abuse and 30 had sought
      other family services. Hypotheses were derived from several frameworks relevant
      to understanding abuse--intrapsychic (learned helplessness), interpersonal
      (family violence), and feminist theory. Findings related to the specific
      formulations were subsequently combined into a model of abuse in which the
      mutuality of communication within the couple mediates the effects of husband's
      intoxication and environmental stressors on the occurrence/severity of abuse. The
      study points out the inadequacy of relying on any one existing theory and
      supports the idea of taking an ecological approach to the study of abuse in
      specific populations.

PMID- 7577761
TI  - Abusive behavior in the workplace: a preliminary investigation.
AB  - Dealing with hostile interpersonal relationships at work has been the topic of
      many popular books and workshops. Yet, with the exception of sexual harassment,
      there is surprisingly little mention in the organizational research literature on
      the nature, extent, and costs of abusive work interactions. These more frequent,
      more tolerated, and, thus, more damaging interpersonal interactions involve
      hostile verbal and nonverbal nonphysical behaviors directed by one or more
      persons towards another. The primary aim is to undermine the other to ensure
      compliance. In this study, we examined the extent to which students experienced
      nonsexual nonphysical abusive behavior on their jobs, the impact of this
      experience on job satisfaction, the characteristics of the actor and target, and
      responses to these behaviors, particularly turnover. The results indicate that
      although most of the students had very positive interactions at work, exposure to
      abusive behavior was familiar, was relatively frequent, and had a negative impact
      on the targets. The actors tended to be bosses and older than the targets. The
      quality of the interpersonal relationships at work was related to job
      satisfaction and intention to leave. The implications of these results are
      discussed with respect to individual, situational, and organizational factors
      that may be related to the presence and impact of abusive interpersonal
      interactions. Avenues for research on the nature, extent, and impact of these
      behaviors at both the individual and organizational levels are identified.

PMID- 7577762
TI  - Domestic abuse by male alcohol and drug addicts.
AB  - Sixty-three male inpatient alcohol and drug addicts and 34 of their female
      partners participated in a study of variables associated with physical and
      nonphysical abuse of women. Results suggest that domestic abuse by male addicts
      is not directly related to experience of violence or addiction in the family of
      origin, external locus of control, or severity of alcohol abuse. Correlates of
      domestic abuse were an early onset of drug/alcohol-related problems; low income;
      a history of nonalcohol drug use, particularly cocaine; and a history of arrest
      and outpatient counseling.

PMID- 7577763
TI  - Constitutional challenges to child witness protection legislation: an update.
AB  - The Supreme Court's landmark decision in Maryland v. Craig created some
      uncertainty about the state constitutionality of child witness protection
      legislation. This article briefly discusses the current status of child witness
      protection legislation in light of recent litigation, focusing on Illinois.
      Conclusions are drawn concerning the likely future course of litigation affecting
      child witness protection legislation in other jurisdictions.

PMID- 7577765
TI  - Developmental abnormalities and cortical sulcal enlargement in psychosis.
AB  - Neurodevelopmental abnormalities and cortical sulcal enlargement both occur in
      schizophrenia. To test the hypothesis that these abnormalities were related, CT
      scans from 164 psychotic patients (80 with schizophrenia) were reviewed.
      Neurodevelopmental abnormalities were observed in 11%. Abnormalities were equally
      prevalent in schizophrenia and other psychotic disorders. Cortical sulcal
      enlargement was observed in 39% of patients with schizophrenia, and was not
      associated with developmental abnormalities. Different mechanisms may contribute
      to distinct structural abnormalities.

PMID- 7577764
TI  - Childhood behavioral precursors of adult symptom dimensions in schizophrenia.
AB  - The present investigation tested the hypothesis that childhood behavioral
      problems are differentially associated with clinical symptoms in adult-onset
      schizophrenia. Parents of 29 schizophrenic patients completed questionnaires
      concerning (1) the childhood behaviors of all their offspring from birth through
      15 years of age, and (2) the symptomatology of their schizophrenic offspring. The
      childhood behavior scale was a modified version of Achenbach's Child Behavior
      Checklist (1991). Scores were derived for six childhood behavior problem factors:
      Withdrawal, Anxiety/Depression, Social Problems, Thought Problems, Attention
      Problems, and Aggression/Delinquency. Ratings of symptoms were based on parental
      versions of Andreasen's Scale for the Assessment of Positive Symptoms (SAPS;
      1983) and Scale for the Assessment of Negative Symptoms (SANS; 1981).
      Symptomatology scores were computed from the SANS and SAPS following Malla et
      al.'s (1993) and Liddle's (1987b) tri-dimensional concept of schizophrenia:
      Reality Distortion, Psychomotor Poverty and Cognitive Disorganization. Regression
      analyses were conducted to examine the relation between childhood behavior and
      adult symptomatology in the schizophrenic patients. The results indicated that
      the Psychomotor Poverty and Cognitive Disorganization dimensions in adult
      patients are positively associated with Withdrawn behavior and inversely
      associated with Anxious/Depressed characteristics in childhood. The results are
      discussed in light of the distinction between primary and secondary negative
      symptoms, and the three dimension concept of schizophrenia.

PMID- 7577767
TI  - The effects of cognitive complexity on a social sequencing task in schizophrenia.
AB  - Information processing research has suggested that the schizophrenia patient's
      performance on cognitive tasks is significantly diminished by the complexity of
      that task. The effects of cognitive complexity on a social cognitive task
      sequencing actions that describe a social situation-were examined in this study.
      A task comprising short and long temporal sequences was administered to 26
      subjects with DSM III-R diagnosis of schizophrenia. Differences in discriminating
      power across the short and long sequences in this task were diminished using
      standardization and cross-validation samples of normal control subjects. Results
      showed that schizophrenia patients earned significantly lower scores on the
      longer sequences. Additional analyses showed that the differential deficit was
      significantly associated with negative symptoms of social withdrawal and
      retardation but not with thinking disturbances associated with positive symptoms.
      Understanding deficits in processing situational schemata may lead to better
      models of the cognitive underpinnings of social functioning in schizophrenia.

PMID- 7577766
TI  - Posterior superior temporal gyrus in schizophrenia: grey matter changes and
      clinical correlates.
AB  - We report an MRI morphometric study of the posterior segment of the superior
      temporal gyrus (STG) in twenty young male schizophrenics and their individually
      matched normal controls. In particular the more posterior segment of STG was
      examined, since it has been identified as the approximate site of Wernicke's
      language area and is a marker for the planum temporale, a region believed to be
      abnormal in schizophrenia. Total volumes and grey and white matter volumes were
      measured in middle and posterior STG in each hemisphere. STG grey matter volumes
      and percentages were significantly reduced bilaterally in both regions in
      schizophrenic subjects. No significant differences between patients and controls
      were noted in STG white matter volumes. A significant correlation was detected
      between delusion scores in schizophrenics and the total volume of the left
      dominant posterior STG. Replicating the findings of a recent study (Shenton et
      al., 1992), we found an inverse correlation between thought disorder scores and
      grey matter reduction in the left posterior STG in schizophrenia.

PMID- 7577769
TI  - The development and reliability of the Mental Health Research Institute Unusual
      Perceptions Schedule (MUPS): an instrument to record auditory hallucinatory
      experience.
AB  - The Mental Health Research Institute Unusual Perceptions Schedule (MUPS) is a
      comprehensive instrument developed to record subjects' experiences of auditory
      hallucinations as completely as possible. The Schedule comprises a semi
      structured interview and documents the physical characteristics of auditory
      hallucinations such as their onset and course, number, volume, tone, location, as
      well as other phenomena associated with them such as delusions. In addition,
      other aspects of hallucinations, such as coping strategies, contributing factors
      and subjects' personal views and reactions are also explored. In a sample of 100
      subjects drawn primarily from the in-patient wards at Royal Park Hospital the
      MUPS was found to be an acceptable instrument to subjects in the field.
      Interrater reliability assessed in a subsample of 30 subjects was found to be
      high at the level of the individual items. Whether used in whole or part, the
      MUPS provides a reliable and acceptable method of assessing patients' experience
      of auditory hallucinations.

PMID- 7577768
TI  - Information processing during eye tracking as revealed by event-related
      potentials in schizophrenics, alcoholics, and healthy controls.
AB  - To further explore the hypothesis that schizophrenics are more distractable
      and/or have reduced processing resources available, event-related potentials
      (ERPs) and smooth pursuit eye movements (SPEM) were investigated in 20 medicated
      schizophrenics, 19 detoxified chronic alcoholics, and in a control group of 20
      healthy subjects. Groups were matched for age and education. Eye tracking tasks
      and auditory oddball tasks were performed separately as well as simultaneously.
      In addition, an eye tracking condition with a task-irrelevant tone sequence was
      used to assess the effect of distraction. Schizophrenics showed a trend for
      poorer SPEM performance; alcoholics had no dysfunction in this task. Tracking
      accuracy did not change in either group when additional auditory stimuli were
      presented. P300 latency was delayed in both schizophrenics and alcoholics. P300
      amplitude showed no overall group difference but it increased during the dual
      task in normals whereas it remained constant in patients. N100 amplitude was
      generally larger during the more complex conditions indicating heightened
      unspecific arousal. It is suggested that normals use increased arousal to
      mobilize additional resources and to allocate them to stimulus evaluation but
      schizophrenics and alcoholics are unable to do so. Results are more conform to a
      limited resources concept than to a filter deficit model of cognitive
      disturbances in schizophrenia and alcoholism.

PMID- 7577771
TI  - Morphological changes associated with scraping procedures in cultured cells from
      schizophrenic and control skin donors.

PMID- 7577770
TI  - Prevalence of psychosis among the Hutterites: a reanalysis of the 1950-53 study.
AB  - Psychiatric case records from Eaton and Weil's 1950-53 study of the Hutterites
      were rediagnosed using DSM-III-R criteria. The results confirmed that the
      Hutterites have a very low prevalence of both schizophrenia (0.9 per 1000) and
      bipolar disorder (0.6 per 1000). Genetic and/or environmental explanations are
      both possible. Because of their unusual genetics and lifestyle, the Hutterites
      are an invaluable potential research resource.

PMID- 7577772
TI  - Multiple rape trauma followed by delusional parasitosis. A case report from the
      Bosnian war.

PMID- 7577773
TI  - Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for
      common ground.
AB  - Two of the favorite hypotheses of schizophrenia research-maldevelopment of
      cerebral cortex and malfunction of brain dopamine systems-have often seemed
      difficult to reconcile. This article reviews recent research that suggests a
      heuristically useful reconciliation centered on the functional neuroanatomical
      concept of prefrontal-temporolimbic cortical connectivity. Anatomical findings
      from postmortem studies and neuropsychological and neuroimaging studies of brain
      function in patients with schizophrenia have implicated a developmental
      'dysconnection' of temporolimbic-prefrontal cortices. The possibility that such
      dysconnection can account for the principal phenomenology of the illness,
      including its delayed onset and its treatment, is suggested by neurologic disease
      analogies such as metachromatic leukodystrophy and by recent studies in animals
      with developmental cortical lesions. Studies mapping neuronal gene expression
      indicate that all antipsychotic drugs modulate DNA transcription in a region of
      the nucleus accumbens that receives converging inputs from prefrontal and
      temporolimbic cortices, suggesting that indirect compensation for dysfunctional
      communication between prefrontal and temporolimbic cortices is a therapeutic
      mechanism of these drugs. Treatments aimed at direct cortical compensation may be
      more effective.

PMID- 7577775
TI  - Histopathologic changes in primate spinal cord after single and repeated epidural
      phenol administration.
AB  - BACKGROUND AND OBJECTIVES: Epidural phenol for control of pain and spasticity has
      been advocated for clinical use. This study determined the histopathologic
      changes that follow single and repeated epidural administration of phenol in
      saline in nonhuman primates. METHODS: Nine primates received 0.5 mL of either 3%
      phenol in saline (n = 4) or 6% phenol in saline (n = 5) via lumbar epidural
      injection. Two additional primates received three consecutive daily epidural
      doses of 0.5 mL of 3% phenol in saline. Finally, 5 unoperated primates and 5
      primates that received only 2 mL of radiographic contrast material served as
      control subjects. Two weeks after the epidural injection, spinal cords were
      removed and processed for histopathologic study by a neuropathologist blinded to
      the solution administered. RESULTS: None of the control animals demonstrated
      histopathologic changes. One animal that received 6% phenol died 3 days after
      injection. All phenol-treated animals demonstrated predominantly posterior root
      damage. Spinal cord damage was seen in all animals receiving 6% phenol, in 2
      animals receiving 3% phenol single doses, and in neither animal receiving 3%
      phenol multiple doses. Anterior root damage occurred in all phenol-treated
      animals except the 4 that received single 3% phenol injections. Animals that
      received 6% phenol demonstrated greater lower extremity motor weakness than those
      in the other groups, but no clear correlation existed between extent of
      histopathologic changes and motor weakness. CONCLUSIONS: Motor weakness, anterior
      root damage, and direct cord injury were noted in primates following epidural
      administration of phenol in concentrations below what has been reported for
      clinical use in humans. Since it is more difficult to control the spread of
      epidural versus subarachnoid phenol, the risks of epidural phenol may outweigh
      the benefits relative to subarachnoid administration.

PMID- 7577774
TI  - 1994 John J. Bonica Lecture. The clinical effects of morphine pharmacology.
AB  - BACKGROUND AND OBJECTIVES: The literature is replete with studies of morphine. It
      is not surprising that some viewpoints expressed tend to be often repeated
      without critical analysis. The goal of this lecture is to probe some commonly
      held viewpoints about the pharmacology of morphine. This involves retracing some
      of its history, re-examining its physicochemical nature, re-evaluating its
      physiologic disposition and the pharmacologic activity of its metabolites.
      METHODS: The background material selected for inclusion consists of historic
      pharmacologic secondary sources, selections from the recent primary literature on
      morphine pharmacokinetics and metabolism, and vignettes from the author's
      personal research in progress with colleagues in Australia. RESULTS: The author's
      perspective is that of a chemical pharmacologist with more than a passing
      interest in pharmacokinetics. The synthesis evaluates the therapeutic
      consequences of the pharmacologic aspects chosen. CONCLUSIONS: Morphine in
      various forms has been used successfully in the alleviation of pain for at least
      several millenia but it is only relatively recently that a rationale for its
      action has been found. Morphine is a relatively poorly lipophilic opioid but
      equilibrates with tissue of the brain relatively easily. While the metabolism of
      morphine occurs in the liver, it is metabolized in the kidneys and brain as well.
      The clearance of morphine is not notably decreased by renal dysfunction, but
      clearance of its glucuronide metabolites is decreased markedly. While the
      metabolites produced may be shown to be pharmacologically active in particular
      experimental preparations, it is not yet certain that they contribute
      pharmacologically after systemic administration of morphine in experimental
      animals or humans with generally normal physiology.

PMID- 7577776
TI  - The effect of pre-emptive fentanyl on formalin pain in mice.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to determine if pre-emptive
      systemic fentanyl administration would decrease the amount of formalin pain in
      mice. METHODS: Under halothane anesthesia, formalin was injected in the hindpaw
      of mice. The animals were randomly assigned to receive no systemic fentanyl
      (group 1; n = 20); subcutaneous fentanyl, 50 micrograms/kg 5 minutes prior to
      formalin injection (group 2; n = 20); or subcutaneous fentanyl, 50 micrograms/kg
      5 minutes after formalin injection (group 3; n = 20). After recovery from
      anesthesia, the formalin-induced paw-licking response was observed for 1 hour.
      The time to first paw lick, the number of paw licks, and the duration of paw
      licking were compared among the groups with an analysis of variance. RESULTS: The
      fentanyl-treated mice in groups 2 and 3 had a significantly longer time to first
      paw lick, had a lower number of paw licks, and had a shorter duration of paw
      licking compared to the control mice in group 1. There was no significant
      difference in formalin pain behavior between the mice receiving fentanyl before
      or after formalin injection. CONCLUSIONS: Pre-emptive administration of
      subcutaneous fentanyl does not decrease the severity of acute pain in mice.

PMID- 7577778
TI  - Effects of epidural bupivacaine after thoracotomy.
AB  - BACKGROUND AND OBJECTIVES: Combinations of bupivacaine and fentanyl are popular
      for postoperative epidural analgesia. However, there are little data from which
      to select a rational dose of bupivacaine. The study examined the effects of
      increasing amounts of epidural bupivacaine on postoperative analgesia, epidural
      fentanyl consumption, and side effects after thoracotomy. METHODS: Twenty-four
      patients were randomized in a double-blind manner to receive intra- and
      postoperative epidural infusions of either saline, 0.01% bupivacaine, 0.05%
      bupivacaine, or 0.1% bupivacaine at 10 mL/h. All patients received a standardized
      combined epidural (120 mg lidocaine and 1.5 micrograms/kg of fentanyl) and
      general anesthesia. Further postoperative analgesia was provided with fentanyl
      patient-controlled epidural analgesia (PCEA) only. RESULTS: There were no
      differences between groups in visual analog scale (VAS) pain scores at rest or
      cough, but 10 and 5 mg/h of bupivacaine provided better analgesia during
      physiotherapy (P < .05). The use of 10 and 5 mg/h of bupivacaine led to
      significant opioid sparing (50% decrease) when compared to saline and 1 mg/h
      bupivacaine (P < .03). There was a trend toward a greater incidence of
      orthostasis with the use of bupivacaine at 10 mg/h (P = .09). Incidences of
      opioid side effects were not different between groups. CONCLUSIONS: The results
      demonstrate improved analgesia with physiotherapy and significant opioid sparing
      when 10 and 5 mg/h doses of bupivacaine are used. However, the incidence of
      orthostasis may be increased with the use of 10 mg/h. Thus, 5 mg/h of epidural
      bupivacaine (.05% at 10 mL/h) improved analgesia, decreased opioid requirements,
      and did not have detectable hemodynamic effects.

PMID- 7577777
TI  - Can pre-emptive interpleural block reduce perioperative anesthetic and analgesic
      requirements?
AB  - BACKGROUND AND OBJECTIVES: The hypothesis that preoperative interpleural block
      might reduce intraoperative anesthetic and analgesic requirements and modify the
      intensity of postoperative pain was examined in this double-blind, randomized,
      saline-controlled study. METHODS: Thirty women undergoing cholecystectomy with
      subcostal incision were included. All patients received a background isoflurane
      anesthetic in 40% O2 and air. Interpleural catheters were inserted after
      induction of anesthesia and 20-25 minutes before surgical incision. Patients were
      randomly allocated to one of two groups. Group 1 received a bolus of 0.5% plain
      bupivacaine followed by a continuous infusion of 7 mL/h 0.25% bupivacaine. Group
      2 received similar bolus volume and infusion of 0.9% saline. The attending
      anesthesiologist was blinded to patient groups. Intraoperative analgesia was
      assessed by the hemodynamic responses to surgery and by the anesthetic and
      analgesic requirements. Postoperative analgesia was accomplished by 20 mL
      bupivacaine 0.5% in group 2 patients followed by an infusion of bupivacaine 0.25%
      in the two groups. Postoperative analgesia was assessed by visual analog scale (0
      10), hourly bupivacaine requirements, peak expiratory flow rate, and the request
      for additional intramuscular morphine. RESULTS: Preoperative interpleural block
      produced a significant decrease in mean arterial pressure and heart rate. These
      hemodynamic changes were partly corrected by surgical incision and reduction of
      isoflurane concentration. The mean intraoperative isoflurane requirements in
      group 1 and 2 were, respectively, 0.59 +/- 0.02% and 1.2 +/- 0.12% (P < .001).
      Preoperative instillation of bupivacaine in the pleural space resulted in about
      50% reduction in isoflurane requirements. Intraoperative alfentanil requirements
      were 13.6 +/- 6 and 29.2 +/- 11 micrograms/kg in the bupivacaine and saline
      groups, respectively (P < .001). After the operation, both study groups had
      comparable visual analog scale peak expiratory flow rate, bupivacaine infusion
      rate, and intramuscular morphine supplements. CONCLUSIONS: Preoperative
      interpleural block, during a background isoflurane anesthetic, reduces the
      hemodynamic response to surgery and the intraoperative anesthetic and analgesic
      requirements. Preoperative interpleural block with plain bupivacaine results in
      significant reductions in mean arterial pressure and heart rate, probably related
      to unilateral sympathetic block and the concomitant use of isoflurane. The timing
      of interpleural block, that is, pre-emptive versus postoperative, does affect the
      intensity of postoperative pain or the request for supplementary analgesia.

PMID- 7577779
TI  - Effects of brachial plexus fentanyl on supraclavicular block. A randomized,
      double-blind study.
AB  - BACKGROUND AND OBJECTIVES: The study examined the effects of adding fentanyl to
      mepivacaine supraclavicular blocks on block characteristics and postoperative
      analgesia. METHODS: Twenty patients undergoing upper extremity surgery with
      supraclavicular blocks were prospectively randomized to receive 75 micrograms
      fentanyl either added to the local anesthetic (30 mL mepivacaine 1.5% with
      epinephrine 5 micrograms/mL) or given intramuscularly. An equivalent volume of
      normal saline was given in one of the two sites as a control in a double-blind
      fashion. Sensory and motor block onset, time to completion, and duration were
      measured. After the operation, patient-controlled analgesia with morphine was
      administered and the total dose used over 24 hours recorded. Visual analog pain
      scale (VAS: 0 = no pain, 10 cm = worst pain) was measured at 0, 1, 2, 3, 4, and
      12 hours after the operation. RESULTS: There was no statistically significant
      difference between the two groups in sensory or motor block characteristics.
      There was a significantly lower VAS score among the patients with fentanyl added
      to their blocks within the first hour after the operation (1.3 +/- 1.5 cm versus
      3.8 +/- 3.1 cm; P < .05), but subsequent VAS scores and total 24-hour patient
      controlled analgesia requirements were no different. CONCLUSIONS: Adding fentanyl
      75 micrograms to mepivacaine supraclavicular blocks has no significant effects on
      block characteristics. It may enhance postoperative analgesia, but the duration
      of this effect is too brief to be clinically useful.

PMID- 7577780
TI  - The response of umbilical vessels, with and without vascular endothelium, to
      local anesthesia in low PO2 and hypercarbia.
AB  - BACKGROUND AND OBJECTIVES: Human umbilical vessels are sensitive to local
      anesthetic agents as well as to a variety of other exogenous and endogenous
      substances. Changes in blood gases such as hypoxia and hypercarbia may alter
      these responses. This study examined the effects of local anesthetic agents under
      these conditions and how the effects are related to the vascular endothelium.
      METHODS: Veins and arteries, dissected from umbilical cords of healthy newborns,
      were cross-sectioned to form rings. The rings were mounted in a muscle chamber
      containing Krebs-Ringer bicarbonate solution that was gassed to approximate
      control, low PO2 or hypercarbic conditions. Changes in isometric tension were
      recorded in response to increasing concentrations of bupivacaine (B), lidocaine
      (L), or 2-chloroprocaine (2-CP). In half the experiments, intimal rubbing was
      used to remove the endothelium of rings for the purpose of disclosing the role of
      endothelial-derived factors. RESULTS: The normal contracting (increasing baseline
      tone) or relaxing (decreasing baseline tone) responses to local anesthesia were
      unchanged by hypercarbia, but low PO2 suppressed the relaxing effect of 2-CP on
      arteries. Removal of endothelium enhanced the relaxing effect of 2-CP on
      arteries, and unmasked a contracting effect of L on arteries. Rubbed vessels,
      while exposed to low PO2 or hypercarbia, became less responsive to 2-CP.
      CONCLUSIONS: Changes in the internal environment are capable of altering the
      response of umbilical vascular smooth muscle to local anesthesia. Additionally,
      the vascular endothelium appears to influence the degree of response to
      anesthesia.

PMID- 7577781
TI  - Ultrasound imaging for stellate ganglion block: direct visualization of puncture
      site and local anesthetic spread. A pilot study.
AB  - BACKGROUND AND OBJECTIVES: Stellate ganglion block (SGB) inhibits sympathetic
      innervation and is a common treatment for reflex sympathetic dystrophy. During
      the positioning of the needle, there is a risk of injury to the adjacent
      structures. The aim of the study was to develop an ultrasonographic imaging
      technique for the performance of SGB. METHODS: Twelve patients (ASA I-II)
      underwent SGB first by using the blind standard technique (group A: 8 mL
      bupivacaine 0.25%) and a second time by using an ultrasonographic imaging
      technique (group B: 5 mL bupivacaine 0.25%). In group B a 10 MHz ultrasound
      scanning probe was used to identify the anatomic structures and to guide the
      needle toward the transverse process of C6. RESULTS: Stellate ganglion block was
      satisfactory in 11 of 12 attempts by the blind technique. Ultrasonographic
      guidance (group B) resulted in a complete block in all patients. Onset of block
      was observed within 10 minutes in only 10 of 12 group A patients, while all
      patients in group B exhibited an adequate block after 10 minutes. During the
      imaging technique, the needle was inserted to an average depth of 22 +/- 3 mm and
      the injection of 5 mL bupivacaine resulted in an anesthetic depot with a mean
      diameter of 14 +/- 3 mm. Distance from the depot to the vagal nerve was 5 +/- 3
      mm and 5 +/- 4 mm to the root of C6. All patients (n = 4) with a distance of < 1
      mm between anesthetic depot and the root of C6 developed paresthesia within the
      corresponding cutaneous segment. Blind technique resulted in hematoma formation
      in three study patients, with no hematoma occurring during imaging technique.
      CONCLUSIONS: Ultrasonographic guided SGB may improve safety and allows the
      visualization of the local anesthetic depot. Studying the local anesthetic spread
      might allow the avoidance of side effects as well as typical complications of
      SGB.

PMID- 7577782
TI  - Postulated mechanisms for postdural puncture headache and review of laboratory
      models. Clinical experience.

PMID- 7577783
TI  - Topography of peribulbar anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Peribulbar anesthesia has fewer complications than
      retrobulbar anesthesia, but ocular perforation has also been described in
      peribulbar anesthesia. This study aims to verify by computed tomography that the
      recommended points for performing peribulbar anesthesia are safe. METHODS: Three
      human corpses were used. The puncture points were position A (superior internal
      orbital angle and inferior external orbital angle), position B (superior and
      inferior orbital median line), and position C (superior external and inferior
      internal orbital angle). Contrast diffusion was studied in each position at 3, 4,
      5, and 10 minutes after contrast injection. RESULTS: Among upper eyelid
      punctures, the only one anatomically safe is the internal angle puncture, given
      that either in the median line or the external angle there is a chance of eye
      globe perforation. Lower eyelid positions are a safe distance from the optic
      nerve and ocular globe. Contrast diffusion was satisfactory in positions A and B.
      There was little diffusion in position C. CONCLUSIONS: The median or external
      superior angle eyelid puncture may cause eye globe perforation.

PMID- 7577785
TI  - Rectus syndrome. Another cause of upper abdominal pain.
AB  - BACKGROUND AND OBJECTIVES: Rectus syndrome is somatic pain originating from the
      rectus abdominis musculature of the abdomen. However, pain with its associated
      somatovisceral symptoms such as nausea, vomiting, and anorexia, is called
      pseudovisceral pain syndrome. It commonly mimics abdominal visceral pain and
      misleads medical practitioners into establishing a wrong diagnosis and giving
      inadequate pain management. Owing to its primary somatic origin, a regional
      rectus nerve block is an efficacious modality for use in differentiating the
      diagnosis and providing longlasting optimal pain relief. METHODS: Two cases, a 48
      year-old man and a 41-year-old woman, were referred for the management of chronic
      upper abdominal pain consistent with chronic pancreatitis. They underwent rectus
      block, first to differentiate the diagnosis and then to relieve intractable pain
      problems with multidisciplinary pain management. RESULTS: Rectus block was
      performed successfully, and a diagnosis of rectus syndrome was established. These
      two patients responded to the rectus block immediately and received long-lasting
      pain relief after repeated rectus blocks in conjunction with pharmacologic and
      psychological treatment and physiotherapy. CONCLUSION: Rectus syndrome could be
      another potential cause of chronic intractable upper abdominal pain problem;
      rectus block provides a simple diagnostic and therapeutic technique to
      differentiate the diagnosis and treat it adequately.

PMID- 7577784
TI  - Suprascapular nerve block by catheter for breakthrough shoulder cancer pain.
AB  - BACKGROUND AND OBJECTIVES: Incidental shoulder pain due to movement renders pain
      control difficult because it requires high basal dosages or additional doses of
      opioids. Shoulder pain can be alleviated by suprascapular nerve block, and the
      placement of a catheter can permit the injection of local anesthesia as needed.
      METHODS: In a patient with lung cancer and continuous chest pain well controlled
      by opioids but with shoulder breakthrough pain necessitating extra doses of
      opioids, a suprascapular nerve block was performed via an indwelling catheter.
      RESULTS: The breakthrough events due to scapular involvement were treated with
      local injections of 5 mL bupivacaine 0.5% until death (4 weeks later) without any
      complications. CONCLUSIONS: Continuous suprascapular nerve block is safe and
      simple and has proven to be useful in avoiding extra doses of opioids.

PMID- 7577787
TI  - Computed tomography-guided intercostal cryoanalgesia: a new technique.

PMID- 7577786
TI  - Transient paraplegia following alcohol celiac plexus block.
AB  - BACKGROUND AND OBJECTIVES: A pancreatic cancer patient developing transient
      paraplegia compatible with spinal cord ischemia, following alcohol celiac plexus
      neurolysis, is described. METHODS: A 58-year-old man with metastatic pancreatic
      cancer underwent celiac (deep splanchnic) alcohol neurolysis for management of
      severe epigastric and midback pain. In spite of apparently adequate needle
      position, he developed transient paraplegia consistent with anterior spinal
      artery syndrome. RESULTS: The clinical findings suggest ischemia of the anterior
      spinal cord with complete motor and sensory paralysis to a T8 spinal cord level
      resulting from an anterior spinal artery syndrome. CONCLUSIONS: The cause of the
      limited bilateral transient paralysis following celiac plexus block in this
      patient may involve ischemia of the spinal cord associated with reversible
      arterial spasm following the injection of ethanol solution.

PMID- 7577788
TI  - A regional anesthetic technique for ankle arthroscopy.

PMID- 7577789
TI  - Correct dose of tetracaine in infants.

PMID- 7577790
TI  - A new look at lumbar epidural space pressure.

PMID- 7577791
TI  - Treatment of supraventricular tachycardia under spinal anesthesia.

PMID- 7577792
TI  - Comment on anesthesia technique described by Eldor.

PMID- 7577793
TI  - Aseptic meningitis due to metallic particles in the needle-through-needle
      technique.

PMID- 7577794
TI  - alpha beta and gamma delta T cells in the immune response to the erythrocytic
      stages of malaria in mice.
AB  - Mice lacking T cells with alpha beta TCR (TCR beta-/-) or gamma delta TCR (TCR
      delta-/-) were infected with the erythrocytic stages of the malaria parasite,
      Plasmodium chabaudi chabaudi (AS). Mice without gamma delta T cells could control
      and reduce a primary infection of P. chabaudi with a slight delay in the time of
      clearance of the acute phase of infection and significantly higher recrudescent
      parasitaemias compared with control intact mice. TCR delta -/- mice had higher
      levels of both serum Ig and malaria-specific antibodies of the isotypes IgG3 and
      IgG1 compared with control mice. TCR beta -/- mice, despite a striking increase
      in NK1.1+ cells and the presence of gamma delta T cells, were unable to clear
      their infection. Although the plasma of TCR beta -/- mice contained all Ig
      isotypes before and during a primary infection, they were unable to produce
      significant levels of malaria-specific IgG antibodies, suggesting that in the
      absence of alpha beta T cells gamma delta T cells are not able to provide
      efficient help for antibody production.

PMID- 7577795
TI  - The status of Ig loci rearrangements in single cells from different stages of B
      cell development.
AB  - Differential expression of c-kit, CD25 (TAC), surrogate L chain and cytoplasmic
      muH chain, and surface expression of IgM and IgD allows the separation of B220
      (CD45+) B cell subpopulations. PCR analyses with DNA of single cells developed by
      others and by us have been used to monitor the conformation of the Ig H and L
      chain gene loci in these different B lineage subpopulations. The results of these
      analyses indicate that B220+/c-kit+/CD25- cells are the precursors of large
      B220+/CD25+/sIgM- which, in turn, are the precursors of small B220+/CD25+/sIgM-
      cells. The majority of B220+/c-kit+/CD25- cells are DHJH-rearranged, with L chain
      loci in germline configuration and are thus pre-B I cells. More than 90% of all
      large B220+/CD25+/sIgM- cells have at least one H chain locus VHDHJH rearranged;
      half of them have also the second locus VHDHJH rearranged and are thus large pre
      B II cells. Rearrangements of at least one allele of the kappa L chain loci
      become detectable in 65% of the small B220+/CD25+/sIgM- cells, 67% of the
      immature B and > 75% of the mature B cells. The ratio of kappa L to lambda L gene
      rearrangements in all three subpopulations is approximately 10:1, indicating that
      the kappa L/lambda L ratio is established as soon as rearrangements are made.

PMID- 7577796
TI  - Th1 and Th2 help for B cells: differential capacity for induction of autonomous
      responsiveness to IL-2.
AB  - Sustained interaction with Th1 cells has been shown to induce IL-2 responsiveness
      by murine B cells. This is equivalently dependent on CD40, CD54/ICAM-1 and MHC II
      ligation, and co-cross-linking of CD54 and MHC II in the presence of IL-5 up
      regulates a functional IL-2R on B cells. We now show that IL-5 (125 U/ml)
      synergizes with Th1 cells to induce B cell responses to IL-2, that are maintained
      following T-cell removal, e.g. autonomous. Th1 help in the absence of IL-5
      resulted in weak or undetectable responses following T cell removal. The
      mechanism of IL-5 synergy involved persistence of IL-2R beta expression following
      T cell removal, as opposed to enhancement of IL-2R induction or function. The
      level of contact-induced IL-2R expression on B cells was not itself modified by
      IL-5. The effects of IL-5 did not overcome the requirement for T contact signals
      and treatment of B cells with soluble anti-Ig did not circumvent the need for IL
      5 for autonomous IL-2 responses. Consistent with the above, interaction with an
      IL-5-producing Th2 clone induced strong autonomous B cell responses to IL-2.
      Qualitative differences of Th2 help over that of Th1 may thus be attributable to
      their differential ability to induce autonomous B cell responsiveness to
      cytokines. This may be representative of events in which maintenance of cell
      cycle is important, as is the case in germinal centers.

PMID- 7577797
TI  - CD28 ligands CD80 (B7-1) and CD86 (B7-2) induce long-term autocrine growth of
      CD4+ T cells and induce similar patterns of cytokine secretion in vitro.
AB  - The interaction of CD28 and its ligands is critical for antigen-induced T cell
      activation. Recent studies have demonstrated the existence of at least two
      members of the B7 receptor family. In this report, the co-stimulatory signals
      provided by CD80 (B7-1) or CD86 (B7-2) were compared to CD28 ligation by mAb. We
      demonstrate that the kinetics of induction of T cell proliferation after anti-CD3
      stimulation was similar regardless of the form of co-stimulation. Similarly, B7-1
      and B7-2 could both maintain long-term expansion of CD4 cells. The co-stimulatory
      effects of both B7-1 and B7-2 were dependent on CD28 cross-linking, based on
      complete inhibition of proliferation by CD28 antibody Fab fragments. Co
      stimulation with B7-1 and B7-2 induced high levels of cytokine secretion by
      resting T cells, and the effects of B7-1 and B7-2 could not be distinguished.
      This conclusion is based on analysis of the initial activation of CD28+ T cells,
      as well as T cell subpopulations consisting of CD4+ and CD8+ T cells. Both B7-1
      and B7-2 could elicit IL-4 secretion from CD4+ T cells while anti-CD28 antibody
      induced substantially less IL-4 secretion. Furthermore, both B7-1 and B7-2 could
      stimulate high levels of IFN-gamma and IL-4 from CD4+CD45RO+ cells, while neither
      B7 receptor could co-stimulate IFN-gamma and IL-4 secretion from CD4+CD45RA+ T
      cells. B7-1 and B7-2 could, however, co-stimulate CD4+CD45RA+ T cells to secrete
      IL-2. By contrast, when previously activated T cells were tested, re-stimulation
      of CD4+ T cell blasts with B7-1 or B7-2 resulted in higher secretion of IL-4 and
      IL-5 than anti-CD28, while re-stimulation with anti-CD28 antibody maintained a
      higher level of secretion of IL-2 and IFN-gamma than B7-1 or B7-2. These
      observations may have important implications because they suggest that the manner
      of CD28 ligation can be a critical determinant in the development of cytokine
      secretion that corresponds to Th1- and Th2-like patterns of differentiation.
      Together these observations suggest that there are no intrinsic differences
      between B7-1 and B7-2 in their ability to co-stimulate the populations of cells
      that we have tested.

PMID- 7577798
TI  - Isolation of a human allo-peptide presented by HLA-B51 molecules.
AB  - Recent studies have demonstrated directly that alloreactive mouse CTL recognize
      peptides presented by MHC class I molecules. However, there is no direct evidence
      that human alloreactive CTL recognize peptides presented by HLA class I
      molecules. We have isolated an HLA-B51 alloreactive CTL clone, 2B3, that did not
      kill the TAP defective cell lines T2 and .174, whereas it killed the TAP-positive
      cell line T1 and .174 cells transfected with TAP genes. These findings suggested
      that this clone recognizes a TAP-dependent allo-peptide. We attempted to isolate
      the human allo-peptide recognized by the 2B3 clone from HLA-B51 molecules. A
      naturally occurring HLA-B*5101 binding peptide isolated from T1 cells was
      recognized by the 2B3 clone. The peptide was also isolated from HLA-B*5101
      molecules purified from C1R-B*5101 cells. In the present study, we directly
      demonstrated that a human alloreactive CTL clone recognizes peptide presented by
      HLA class I molecules.

PMID- 7577799
TI  - Role of maternal antibody in the induction of virus specific and bystander IgA
      responses in Peyer's patches of suckling mice.
AB  - Reciprocal crossings of C.B17 scid/scid and congenic BALB/c (+/+) mice generate
      genetically identical, immunocompetent F1 scid/+ mice that develop in either the
      absence or influence of passively transferred maternal immunity. By exchanging F1
      scid/+ litters at birth among scid/scid, non-immune or reovirus immune BALB/c
      mothers we examined the relative ability of placental or colostral/milk transfer
      of virus specific maternal antibodies to interfere with reovirus immunization of
      the neonatal gut associated lymphoid tissues (GALT). Our data demonstrate that
      the Peyer's patches (PP) in 10-day-old mice are competent to support thymus
      dependent responses to acute reovirus stimulation that include the rapid (within
      3 days) development of specific IgA plasma cells and the subsequent initiation of
      PP germinal center reactions. These neonatal mucosal immune responses occur
      independently of coincident specific maternal immune responses as evidenced by
      the identity of the reovirus specific responses engendered in F1 scid/+ pups of
      scid/scid versus +/+ mothers. However, transfer of pre-existing reovirus specific
      maternal antibody in milk via nursing on a reovirus immune (foster) mother
      completely abrogated reovirus specific neonatal IgA responses; while placental
      transfer of specific maternal antibody alone did not interfere with the
      immunization of the neonatal GALT with enteric reovirus. Reovirus challenge of 10
      day-old mice was associated with a substantial bystander IgA response. Possible
      mechanisms responsible for the induction of the observed bystander IgA responses
      are discussed.

PMID- 7577800
TI  - Dominant and cryptic antigens in the MHC class I restricted T cell response
      across a complex minor histocompatibility barrier: analysis and mapping by
      elution of cellular peptides.
AB  - T cell responses against complex antigens are often directed against a limited
      set of immunodominant determinants. We have studied this phenomenon at the level
      of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor
      histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti
      BALB.B CTL always recognized three reverse phase HPLC fractions in BALB.B
      eluates, whether the latter were obtained from cell lysates or immunoaffinity
      purified class I molecules. One of these immunodominant epitopes (termed IDE-1)
      was H-2Db restricted, and two (termed IDE-2 and IDE-3) were H-2Kb restricted. B6
      mice were immunized with spleen cells from B6 congenic mice carrying single minor
      H loci from BALB.B with the aim to assign IDE to given minor H loci and to
      investigate whether additional epitopes could be identified in the absence of the
      immunodominant ones. IDE-3 was found to be associated to the locus H-28; in
      addition five so called cryptic epitopes were defined. Induction of CTL against
      these epitopes required immunization with cells of the congenic strain; BALB.B
      spleen cells failed to immunize. One subgroup of these epitopes (those associated
      to H-8, H-19 and H-25) were nevertheless found to be processed and loaded in
      class I molecules of BALB.B cells, while there was no evidence for this for H-35
      and H-36. For 10 additional congenic strains, no CTL response was detected. The
      results are discussed in relation to the genetic and molecular basis of minor H
      antigens, and mechanisms for epitope dominance operating at the level of the APC
      or responding T cells.

PMID- 7577801
TI  - Dysregulation of the humoral immune response in old mice.
AB  - The increase in autoantibodies with age of both experimental animals and humans
      has been thought to reflect a shift in the antibody repertoire from foreign to
      self antigens. In mice, before immunization, the age-associated increase in
      antibodies reactive with a prototypic autoantigen, bromelain-treated autologous
      erythrocytes (BrMRBC), reflected a 3-fold increase in serum IgM and the number of
      IgM-secreting spleen cells in old compared with young mice. However, the
      percentage of the IgM-secreting spleen cell repertoire reactive with BrMRBC in
      old mice was actually approximately 50% that in young mice. In contrast, after
      immunization with sheep erythrocytes (SRBC), old mice showed a 5-fold increase in
      the percentage of IgM-secreting cells reactive with BrMRBC while young mice
      showed no significant increase. The converse is true for the percentage of IgM
      secreting spleen cells in old mice specific for SBRC, which is 10% the number
      generated by young mice. The increased autoantibody response of old mice is not,
      however, linked to their poor response to the nominal antigen. Thus, immunization
      with phosphorylcholine (PC) conjugated keyhole limpet hemocyanin, an antigen that
      induces a comparable anti-PC response in old and young mice, also induced more
      autoantibody forming cells in old than young mice. The increased autoantibody
      response of old mice after immunization can be accounted for by both an increased
      number of Ig-secreting spleen cells as well as an increased percentage of the
      expressed repertoire of IgM-secreting spleen cells that react with
      autoantigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577802
TI  - Low avidity recognition of a class II-restricted neo-self peptide by virus
      specific T cells.
AB  - The specificity with which CD4+ T cells recognize self peptides in vivo was
      examined in transgenic mice that express an influenza virus PR8 hemagglutinin
      (HA) polypeptide in many tissues, including the thymus (HA Tg mice). HA Tg and
      non-Tg mice were analyzed for their T cell responses to the major PR8 HA I-E(d)
      restricted CD4+ T cell determinant S1. Negative selection eliminated S1-specific
      T cells from HA Tg mice. Nevertheless, HA Tg mice retained the ability to mount a
      T cell response to a closely related analog of the S1 determinant [S1(K113)], and
      some S1(K113)-specific TCRs displayed a partial reactivity with S1 as indicated
      by their ability to transmit signals for IL-3 but not IL-2 secretion in response
      to the neo-self peptide. Moreover, the neo-self S1 peptide antagonized the
      ability of these TCRs to signal IL-2 secretion in response to the foreign
      S1(K113) determinant. Thus, TCRs that exhibit a partial reactivity with a self
      peptide are present in the peripheral T cell repertoire and can be activated by a
      virus containing an analog of the self peptide. These findings provide a model
      for the induction of autoimmunity by viruses that are close homologs of self
      peptides, and suggest a way in which TCRs could react with self peptides during
      positive selection of developing thymocytes.

PMID- 7577803
TI  - A bispecific antibody prolongs survival in mice bearing lung metastases of
      syngeneic mammary adenocarcinoma.
AB  - In the present study we tested whether T cells retargeted with a bispecific
      antibody (bsAb) could block the growth of lung metastases of syngeneic mammary
      adenocarcinoma in immunocompetent mice. BALB/c mice were injected i.v. with tumor
      and i.p. with a genetically engineered bispecific F(ab')2 [bs(Fab')2] having
      specificity for murine CD3 epsilon chain and for the gp52 mouse mammary tumor
      viral glycoprotein, which is expressed on the tumor cells. The bs(Fab')2 was
      physically stable in blood and serum, was removed from the body with a half-time
      of 12-15 h, and accumulated in lymphoid tissue where it bound to T cells. We show
      that treatment of tumor bearing mice with the bs(Fab')2 significantly prolonged
      their survival relative to untreated controls. Two other genetically engineered
      bs(Fab')2s having specificity for murine CD3 epsilon chain and irrelevant
      antigens did not inhibit tumor growth. In addition, survival was not affected by
      bsAb therapy using a variant tumor cell line that expressed low levels of the
      gp52 target antigen. Inhibition of tumor growth was even more evident by
      histologic analysis. Treatment with the relevant bs(Fab')2 resulted in a marked
      reduction of tumor burden in lung sections taken on days 7, 9 and 11. This is the
      first report demonstrating that a bsAb can inhibit the growth of syngeneic solid
      tumor metastases in mice without addition of T cell activators.

PMID- 7577804
TI  - Both CD28 ligands CD80 (B7-1) and CD86 (B7-2) activate phosphatidylinositol 3
      kinase, and wortmannin reveals heterogeneity in the regulation of T cell IL-2
      secretion.
AB  - In this report, the co-stimulatory signals provided by CD80 (B7-1) or CD86 (B7-2)
      were compared to CD28 ligation by mAb. We demonstrate that while both anti-CD3
      and anti-CD28 antibodies induced activation of phosphoinositide (PI) 3-kinase,
      the kinetics of activation differed. Anti-CD28 produced a sustained activation of
      PI 3-kinase while anti-CD3 induced activation was transient. Both B7-1 and B7-2
      could induce prolonged activation of PI 3-kinase. The co-stimulatory effects of
      B7-1 and B7-2 were dependent on CD28 cross-linking, based on complete inhibition
      of PI 3-kinase activation by CD28 antibody Fab fragments. While Jurkat T cells co
      stimulated with anti-CD3 and B7-1 or B7-2 secreted high levels of IL-2, there
      were distinct effects of anti-CD28 mAb and B7-1 or B7-2 on IL-2 secretion in
      conjunction with protein kinase C activation. To assess functional effects of
      CD28 ligation, pharmacologic inhibitors of PI 3-kinase were evaluated. In Jurkat
      cells, efficient inhibition of PI 3-kinase activation after B7-2 stimulation was
      achieved using wortmannin; however, we observed a surprising increase in IL-2
      secretion after B7 or anti-CD28 stimulation. The effect of wortmannin was
      concentration dependent. Moreover, the effect was specific for receptor-mediated
      activation as wortmannin did not enhance phorbol ester plus ionomycin-induced IL
      2 secretion. Another inhibitor of PI 3-kinase, LY294002, also resulted in
      augmentation of anti-CD28-induced IL-2 secretion by Jurkat cells. The effects of
      wortmannin on IL-2 secretion were also examined in primary T cells. In marked
      contrast, wortmannin resulted in a potent inhibition of anti-CD3 plus B7-1 or
      anti-CD28-induced IL-2 secretion while phorbol ester plus ionomycin-induced IL-2
      secretion was wortmannin resistant. Together these observations demonstrate that
      signal transduction by both B7-1 and B7-2 involves PI 3-kinase, and that PI 3
      kinase or other wortmannin-sensitive targets are important for IL-2 secretion.
      Finally, treatment of Jurkat cells with PI 3-kinase inhibitors alone was
      sufficient to induce low levels of IL-2 secretion. This is consistent with the
      notion that a wortmannin-sensitive target such as PI 3-kinase may down-regulate
      IL-2 secretion in Jurkat cells.

PMID- 7577805
TI  - Antigen-specific down-regulation of myelin basic protein-reactive T cells during
      spontaneous recovery from experimental autoimmune encephalomyelitis: further
      evidence of apoptotic deletion of autoreactive T cells in the central nervous
      system.
AB  - Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by the
      i.v. injection of 10(7) cloned V beta 8.2+ T cells specific for the 72-89 peptide
      of guinea pig myelin basic protein (MBP). Some animals were injected
      simultaneously with 10(7) cloned T cells specific for ovalbumin (OVA).
      Lymphocytes were isolated from the spinal cord and from the peripheral lymphoid
      organs of these rats and the frequencies of MBP-peptide-specific or OVA-specific
      proliferating cells were estimated by limiting dilution analysis at different
      times after cell transfer. The frequencies of cells specific for MBP72-89 or OVA
      in the spinal cord were highest 5 days after cell transfer (MBP72-89, 1 in 1149;
      OVA, 1 in 1116). On day 7, when the rats were recovering, the frequency of cells
      specific for MBP72-89 in the spinal cord fell dramatically to < 1 in 10(5), while
      that of OVA-specific cells decreased to a much lesser extent (1 in 7001). The
      frequencies of MBP72-89-specific cells in the peripheral lymphoid organs during
      and after recovery were also much lower than those of OVA-specific cells. A
      similar pattern of down-regulation of the MBP-peptide-specific, but not the OVA
      specific, T cell response was observed in the spleen and mesenteric lymph nodes
      (MLN) of rats 38 days after the active induction of EAE by immunization with
      equal amounts of MBP and OVA in adjuvants. In the passively transferred model,
      cells isolated from the spinal cord and MLN on day 7 did not regain
      responsiveness to MBP72-89 after incubation with high levels of IL-2, indicating
      that the unresponsiveness was not due to T cell anergy. Thus this study
      demonstrates that there is a specific down-regulation of the MBP72-89-specific T
      cell response during spontaneous recovery from EAE.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577806
TI  - MHC class I expression and CD8+ T cell development in TAP1/beta 2-microglobulin
      double mutant mice.
AB  - We have bred to homozygosity gene disruptions for the transporter associated with
      antigen processing 1 (TAP1) and beta 2-microglobulin (beta 2m), each of which
      plays a distinct role in providing class I MHC subunits. Surface expression of H
      2Kb or Db on cells derived from TAP1/beta 2m -/- mice was undetectable by
      immunofluorescence or immunoprecipitation, unlike the situation observed for TAP1
      -/- and beta 2m -/- single mutant mice. Yet, TAP1/beta 2m -/- cells were able to
      elicit a CD8+ cytotoxic T cell (CTL) response in mice of different H-2 haplotypes
      and could be killed by anti-H-2b specific CTL. Furthermore, TAP1/beta 2m -/- skin
      grafts were rejected by bm1 mutant mice. This suggests that very low levels of
      conformed class I heavy chains can reach the cell surface even in the complete
      absence of TAP1 and beta 2m gene products, and that these molecules may select a
      functional CD8+ T cell repertoire. Indeed, CD4-CD8+ T cells were detected in
      TAP1/beta 2m -/- mice, but in numbers lower than in either of the single mutant
      mice. Nonetheless, it was possible to elicit a CD8+ allospecific and H-2b
      reactive CTL response in TAP1/beta 2m -/- mice. In line with this, TAP1/beta 2m 
      /- mice rapidly rejected TAP1/beta 2m +/- skin grafts. Our results suggest that
      some MHC class I heavy chains in TAP1/beta 2m -/- cells can reach the cell
      surface in a form that allows recognition by allospecific CTL and positive
      selection of CD8+ T cells.

PMID- 7577808
TI  - CD8-dependent CTL require co-engagement of CD8 and the TCR for
      phosphatidylinositol hydrolysis, but CD8-independent CTL do not and can kill in
      the absence of phosphatidylinositol hydrolysis.
AB  - Most instances of MHC class I recognition and target cell killing by CD8+ CTL
      require the involvement of CD8. The role of CD8 in these events may be both for
      adhesion of the CTL with the APC, as well as for signal transduction through the
      TCR. The precise mechanism by which CD8 mediates signal transduction remains
      enigmatic. Similarly, it is unclear whether only the CD8 molecules which bind to
      the same class I molecule as the TCR contribute to signaling in the T cell
      responding to antigen. We have investigated the requirement for co-engagement of
      CD8 and the TCR in the induction of the hydrolysis of phosphatidylinositol-4,5
      bisphosphate (PIP2) during the interaction of CTL and APC transfected with either
      wild-type or mutant (CD8 non-binding) class I molecules. Our results show that
      for conventional CD8-dependent killing co-engagement of both CD8 and the TCR is
      required to initiate PIP2 hydrolysis. This requirement for co-engagement,
      however, can be overcome by a high density of ligand, such as that provided by
      high concentrations of exogenous peptide. In such situations, the binding of CD8
      to non-antigenic class I molecules can elicit PIP2 hydrolysis. Therefore, during
      interactions between CTL and APC, which generally occur at low concentrations of
      antigenic peptide, triggering of PIP2 hydrolysis requires TCR and CD8 co
      engagement, and the binding of CD8 to non-antigenic class I molecules does not
      contribute significantly to signaling within the T cell.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7577807
TI  - Suppression of adult T cell leukemia-derived factor/human thioredoxin induction
      by FK506 and cyclosporin A: a new mechanism of immune modulation via redox
      control.
AB  - Adult T cell leukemia-derived factor (ADF), which is identical to a disulfide
      reducing enzyme human thioredoxin (TRX), is produced and released by activated or
      virus-infected lymphocytes. Here we report that, in peripheral blood mononuclear
      cells (PBMC) stimulated with phytohemagglutinin (PHA), ADF/TRX mRNA was induced
      within 8 h after stimulation as detected by in situ hybridization study. To
      analyze the mechanism of ADF/TRX induction during T cell activation, the effects
      of immunosuppressants including FK506, rapamycin (Rap) and cyclosporin A (CsA) on
      ADF/TRX expression were investigated by immunoblot analysis. ADF/TRX induction in
      PBMC by PHA, Con A or OKT3 mAb was almost completely suppressed by FK506. Whereas
      CsA also inhibited ADF/TRX expression in OKT3 mAb-stimulated PBMC, Rap failed to
      affect it in spite of exhibiting growth inhibition. In addition, exogenous IL-2
      could not increase ADF/TRX production in FK506-treated PBMC or in PHA blasts.
      These results indicate that ADF/TRX induction in T cell activation depends on
      calcineurin-dependent events in the early phase and that IL-2 production is not
      directly involved in ADF/TRX induction. Furthermore, when recombinant ADF (rADF)
      was added to a culture of PBMC 1 h before the addition of PHA and FK506, the
      action of FK506 was partially reversed as determined by [3H]thymidine
      incorporation and viable cell counts. These results suggest that ADF/TRX produced
      and released from PBMC may be a crucial event in lymphocyte activation, and that
      FK506 and CsA may exert the immune suppression partly through inhibiting the
      induction of the endogenous reducing factor ADF/TRX.

PMID- 7577809
TI  - The 3rd International Satellite Symposium on the Conformational Analysis of
      Carbohydrates and Protein/Carbohydrate Interactions. Val Morin, Quebec, Canada,
      24-28 July 1994. Proceedings.

PMID- 7577810
TI  - Application of two-dimensional NMR spectroscopy and molecular dynamics
      simulations to the conformational analysis of oligosaccharides corresponding to
      the cell-wall polysaccharide of Streptococcus group A.
AB  - This paper describes the use of a protocol for conformational analysis of
      oligosaccharide structures related to the cell-wall polysaccharide of
      Streptococcus group A. The polysaccharide features a branched structure with an L
      rhamnopyranose (Rhap) backbone consisting of alternating alpha-(1-->2) and alpha
      (1-->3) links and D-N-acetylglucosamine (GlcpNAc) residues beta-(1-->3)-connected
      to alternating rhamnose rings: [formula: see text] Oligomers consisting of three
      to six residues have been synthesized and nuclear magnetic resonance (NMR)
      assignments have been made. The protocol for conformational analysis of the
      solution structure of these oligosaccharides involves experimental and
      theoretical methods. Two-dimensional NMR spectroscopy methods (TOCSY, ROESY and
      NOESY) are utilized to obtain chemical shift data and proton-proton distances.
      These distances are used as constraints in 100 ps molecular dynamics simulations
      in water using QUANTA and CHARMm. In addition, the dynamics simulations are
      performed without constraints. ROE build-up curves are computed from the averaged
      structures of the molecular dynamics simulations using the CROSREL program and
      compared with the experimental curves. Thus, a refinement of the initial
      structure may be obtained. The alpha-(1-->2) and the beta-(1-->3) links are
      unambiguously defined by the observed ROE cross peaks between the A-B',A'-B and C
      B,C'-B' residues, respectively. The branch-point of the trisaccharide CBA' is
      conformationally well-defined. Assignment of the conformation of the B-A linkage
      (alpha-(1-->3)) was problematic due to TOCSY relay, but could be solved by NOESY
      and T-ROESY techniques. A conformational model for the polysaccharide is
      proposed.

PMID- 7577811
TI  - Treatment of ionic species in force-field calculations: sulfate and carboxylate
      groups in carbohydrates.
AB  - Ab initio computations with different basis sets (up to 6-31 + G* *) on
      methylsulfate and N-methylsulfate anions and on the ionic and neutral forms of
      acetic acid are presented. The atomic charges for the O-sulfo group, computed
      using the Merz-Kollman method at the highest level of theory, were inserted in a
      MM2-derived force-field; its current parametrization affords a 0.22 A root-mean
      square deviation with respect to five crystal structures of sulfated
      monosaccharides.

PMID- 7577812
TI  - The use of CVFF and CFF91 force fields in conformational analysis of carbohydrate
      molecules. Comparison with AMBER molecular mechanics and dynamics calculations
      for methyl alpha-lactoside.
AB  - The solution conformation of methyl alpha-lactoside has been studied through
      molecular mechanics calculations using the AMBER/Homans, CVFF and CFF91 force
      fields, and compared to NMR nuclear Overhauser data. Steady-state and transient
      nuclear Overhauser effects (NOEs) have been interpreted in terms of the ensemble
      average distribution of conformers. The NOEs have been analysed using the
      complete relaxation matrix approach for a rigid and isotropic motion model. The
      molecular mechanics calculations have been performed at two dielectric constants
      (i.e. epsilon = 1 and 80 debyes, or epsilon = r and 80 debyes) in an exhaustive
      way, and, in some cases, have been complemented by specific calculations at
      intermediate epsilon values. Relaxed energy maps and adiabatic surfaces have been
      generated for the different dielectric constants. The probability distribution of
      conformers has been estimated from these steric energy maps. Molecular dynamics
      simulations in vacuo have also been performed. Our results indicate that the beta
      (1-->4) glycosidic linkage shows some fluctuations between three low-energy
      regions, although it spends about 90% of its time in the region close to the
      global minimum. The observed conformation of methyl alpha-lactoside seems to be
      closer to that predicted by CVFF, although the AMBER/Homans results are also in
      qualitative agreement with the experimental data.

PMID- 7577813
TI  - Conformational analysis of the disaccharide alpha-L-Rhap-(1-->2)-alpha-L-Rhap
      OMe: comparison of dynamics simulations with NMR experiments.
AB  - The conformational behaviour of the disaccharide alpha-L-Rhap-(1-->2)-alpha-L
      Rhap-(1-->OMe) has been examined using molecular dynamics (MD) and Langevin
      dynamics simulations and nuclear magnetic resonance (NMR) spectroscopy; an 800 ps
      MD trajectory with the explicit inclusion of water was also determined. The
      results of the MD simulations were found to be sensitive to the choice of
      dielectric constant and force-field parameters. NOE build-up curves were
      constructed from the water and vacuum dynamics trajectories and compared with
      experimental values. Calculation of NOE data sets from the simulations was
      problematic for several reasons, including the similarity in time scales for the
      internal and overall motions.

PMID- 7577814
TI  - Computer modelling of sulfated carbohydrates: applications to carrageenans.
AB  - In this study, X-ray crystallographic data of sulfated monosaccharides have been
      used to derive appropriate parameters for sulfate groups in the Tripos force
      field, previously parameterized for carbohydrates. A database of nine sulfated
      monosaccharides occurring as building blocks of sulfated polysaccharides such as
      carrageenans and sulfated glycosaminoglycans has been built. These tools have
      then been used to evaluate the conformational energies of the repeating units of
      the kappa-, iota- and lambda-carrageenan polymers, taking into account the
      rotation around the sulfate groups. In a third step, helical conformations of
      carrageenans have been explored and the results compared with the experimental
      data obtained by X-ray fibre diffraction. Stable, single, right-handed helices,
      with geometric and helical parameters in close correspondence with the best
      models derived from X-ray diffraction data, have been generated. Finally, the
      configurational statistics of random-coil carrageenan chains have been
      investigated and compared with experimental data currently available on these
      polymers. A highly flexible character is predicted for kappa- and iota
      carrageenans, with lambda-carrageenan showing slightly more extension.

PMID- 7577815
TI  - Conformational analysis of disaccharides using molecular dynamics and NMR
      methods.
AB  - The internal dynamics of four disaccharides, a galacturonic acid dimer, beta
      ethyl-lactoside, sucralose and arabinobiose, have been studied using molecular
      dynamics and nuclear magnetic resonance methods. Theoretical motion models, which
      include order parameters and correlation times for internal motions, were
      extracted from dynamics trajectories in vacuo. In parallel, theoretical NOESY
      volumes were calculated from averaged distance matrices using 'model-free'
      spectral densities. These data were least-squares fitted to the normalized
      experimental NOESY volumes using the order parameters and internal motion
      correlation times as adjustable parameters. The resulting 'experimental' motional
      models were in good agreement with the theoretical ones with the exception of the
      galacturonic acid dimer which was best described by the rigid molecule
      approximation.

PMID- 7577816
TI  - Conformational analysis of segments of oxidized cellulose. Part I: Molecular
      modelling of glucuronic acid dimers considering the effect of counter-ions and a
      polar environment.
AB  - Conformational analysis of various forms of glucuronic acid dimers as the model
      structures of oxidized cellulose has been performed using molecular mechanics
      with a CVFF force field. The effects of ionization of carboxyl groups, ion
      pairing with explicit consideration of counter-ions (Na+, Mg2+) and the implicit
      inclusion of a solvent effect via the dielectric constant, epsilon, have been
      simulated. The non-ionized glucuronic acid dimer shows conformational behaviour
      similar to that of unoxidized cellobiose. The ionization of COOH groups leads to
      strong destabilization of C and D conformers (with both COO- groups on the same
      side of the molecule), while complexation with counter-ions leads to strong
      stabilization of these forms which yield highly wound low-pitch helices. An
      increase in the solvent polarity has an attenuating effect on the behaviour
      described above.

PMID- 7577817
TI  - Conformation and dynamics of a cyclic (1-->2)-beta-D-glucan.
AB  - A molecular modelling and nuclear magnetic resonance spectroscopic study was
      performed in order to gain insight into the conformational preferences of
      cyclosophoroheptadecaose. MM3 molecular mechanics calculations predicted a non
      symmetric conformer with a small cavity of 3.7 A diameter as the lowest energy
      form. Molecular dynamics simulations gave insight into the dynamics of the free
      cyclosophoroheptadecaose and also supported the results of molecular mechanics
      calculations. A fair agreement was found between experimental data and
      corresponding average values predicted by molecular modelling.

PMID- 7577818
TI  - Modelling of the interaction of verotoxin-1 (VT1) with its glycolipid receptor,
      globotriaosylceramide (Gb3).
AB  - Possible binding sites for the glycolipid globotriaosylceramide (Gal alpha 1-
      >4Gal beta 1-->4Glc beta 1-->1 Cer; Gb3) on the B-subunits of verotoxin-1 (VT1)
      were explored using binding data for specifically mutated verotoxins and by
      computational docking of favoured conformers of Gb3 with the crystal structure of
      VT1. Calculations using the GRID program suggested a site with favourable
      hydrophobic interactions at the exposed side chain of Phe30. One of the favoured
      conformers of Gb3 was docked into this site, with the hydrophobic face of the
      internal Gal beta residue in contact with the side chain of Phe30. After energy
      minimization, the two terminal saccharide residues of Gb3 (Gal alpha and Gal
      beta) showed favourable interactions with the toxin. In the proposed model of the
      complex, the terminal Gal alpha of Gb3 is located in proximity to aspartates 16
      18 of VT1. The model is in agreement with available experimental binding data for
      the interaction of globoglycolipids with different naturally occurring and
      mutated verotoxins.

PMID- 7577819
TI  - Conformational features of galacturonans. I. Structure and energy minimization of
      charged and uncharged galacturonan dimeric units.
AB  - Structural parameters (e.g. the geometry, partial charges and dipole moment) of
      the alpha-D-galacturonic residue have been calculated by using semi-empirical
      quantum mechanical methods on several combinations of either the uncharged or
      charged forms, GalAH and GalA-, respectively. Three residue types have been
      explored: (i) the isolated residue, termed GEO1 and GEO1C for GalAH and GalA-,
      respectively; (ii) the residue with a methyl group attached to the O4 and O1
      positions (GEO2 and GEO2C); and (iii) the internal residue in a trimer, e.g.
      GalAH-GalAH-GalAH or the corresponding fully charged version (GEO3 and GEO3C).
      The presence of a charged group in the galacturonate residue and the distribution
      of the excess negative charge on the molecule lead to significant differences in
      the structural parameters in comparison with those of the uncharged galacturonic
      residue. These perceptible differences in internal coordinates of GalAH and GalA-
      residues appear to play a major role in the delimitation of the conformational
      space that is accessible to the dimers, as clearly seen by inspection of the
      conformational maps. Although the overall features seem alike, the maps show that
      the position of the minimum and the shape of the lower energy region
      significantly change if one or both residues in the dimer are charged. The
      relevance of these results for the conformational properties of polygalacturonate
      chains is discussed elsewhere (Ruggiero et al. Int. J. Biol. Macromol. 1995, 17,
      213-218).

PMID- 7577820
TI  - Conformational features of galacturonans. II. Configurational statistics of
      pectic polymers.
AB  - The unperturbed dimensions of poly-alpha-D-galacturonic acid (PGA) as a function
      of the degree of polymerization (n) and degree of ionization (%GalA-) have been
      determined by molecular mechanics and Monte Carlo methods. Chain extensions
      appear to depend substantially on contributions arising from local
      redistributions of charge on charged and uncharged galacturonic acid residues.
      Inclusion of methyl-esterified galacturonic acid units results in increased chain
      extensions. Incorporation of alpha-(1-->2)-L-rhamnose units causes abrupt changes
      in chain propagation and a reduction in calculated chain extension.

PMID- 7577821
TI  - The crystal and molecular structure of 2-sulfamino-2-deoxy-alpha-D-glucopyranose
      sodium salt.2H2O (glucosamine 2-sulfate).
AB  - The crystal and molecular structure of 2-sulfamino-2-deoxy-alpha-D-glucopyranose
      has been determined by direct methods. The crystal belongs to the space group
      P2(1)2(1)2(1) and has unit cell dimensions a = 7.713 A, b = 9.390 A and c =
      17.222 A. The sugar ring has the expected conformation (4C1) and the geometry of
      the N-sulfate moiety is comparable with that found in previous investigations of
      monosaccharide O-sulfates. The sodium ion is octahedrally coordinated involving
      one ring oxygen, two hydroxyls, one sulfate oxygen and two water oxygens.

PMID- 7577822
TI  - Structural fluctuation of methyl N,N'-diacetyl-beta-D-chitobioside in vacuo and
      in aqueous solution: molecular dynamics simulations and proton NMR spectroscopy.
AB  - Molecular dynamics (MD) simulations of methyl N,N'-diacetyl-beta-D-chitobioside
      (GlcNAc beta-(1-->4)GlcNAc beta-OMe) have been performed both in vacuo and in
      aqueous solution with the explicit inclusion of the solvent water molecules. The
      beta-(1-->4) glycosidic linkage fluctuates considerably, over a range of +/- 10
      degrees, in each of the MD simulations in vacuo and in aqueous solution. The
      intra- and inter-residue hydrogen bonds in vacuo are replaced by intermolecular
      hydrogen bonds with the solvent water molecules in aqueous solution. Multiple
      conformations (gg and gt) exist for the exocyclic hydroxymethyl groups. The
      results of the MD simulations are compared with those of 1H-1H nuclear Overhauser
      effect measurements.

PMID- 7577823
TI  - Stedim 6 and Clearflex, two new multilayer materials for infusion containers.
      Comparative study of their compatibility with five drugs versus glass flasks and
      polyvinyl chloride bags.
AB  - Stedim 6 and Clearflex, two new polyethylene-lined materials for infusion bags,
      were studied for their compatibility with disodium clodronate, chlorpromazine and
      maprotiline hydrochlorides, diazepam, and clorazepate dipotassium salt,
      comparatively with borosilicate glass flasks and polyvinyl chloride bags.
      Diazepam, the only drug to exhibit a marked sorption in PVC bags (the loss
      reached 25% of the initial concentration after a contact duration of 72 h),
      showed lower sorption in Stedim 6 bags (loss about 11% under the same conditions)
      and none in Clearflex bags. No significant difference was observed between the
      infusion solutions used as vehicles of the drugs (5% dextrose and 0.9% sodium
      chloride isotonic solutions). The results are discussed in terms of lipophilicity
      of the drugs and crystallinity of the polymers.

PMID- 7577824
TI  - Hydrolytic degradation of benzylated poly(beta-malic acid): influence of sample
      size, sample shape, and polymer composition.
AB  - In order to investigate the effects of sample size, sample shape, and polymer
      composition on the hydrolytic degradation of water-insoluble benzylated poly(beta
      malic acid) derivatives, three polymers were synthesized, namely PMLABe100,
      PMLABe90H10 and PMLABe80H20, containing 100, 90, and 80% of benzyl units
      respectively. For each polymer, 4-mm-thick compression molded pellets, 0.3-mm
      thick casted films and 250-500 microns ground particles were made and allowed to
      age in 0.13 M, pH 7.4 sodium phosphate buffer at 37 degrees C. Degradation was
      monitored by measuring weight changes, variations of polymer composition,
      formation of benzyl alcohol, and molecular weight decreases. It was shown that
      degradation of particles and films depended initially on polymer composition due
      primarily to fast degradation of acid-rich segments present or formed by benzyl
      ester cleavages which led more or less rapidly to similar compositions for the
      three polymers. The higher the content in acid groups, the faster the degradation
      rate and the characteristic changes. It was also found that pellets made of
      PMLABe90H10 or PMLABe80H20 degraded heterogeneously and much faster than
      corresponding films and particles.

PMID- 7577825
TI  - In vivo chondrogenesis in collagen sponge sandwiched by perichondrium.
AB  - In order to increase the cartilage synthesis of the perichondrium, we combined
      auricular perichondrium with a collagen sponge as a template (perichondrium
      sandwiched collagen sponge) and implanted the assembly as an autograft into the
      back of rabbits. Microscopic examination revealed that cartilaginous tissue was
      produced in the collagen sponge and chondrosynthesis was accelerated in the
      collagen sponge implants in comparison with that in materials containing
      perichondrium alone.

PMID- 7577826
TI  - Coadsorption of IgG and BSA onto sulfonated polystyrene latex: I. Sequential and
      competitive coadsorption isotherms.
AB  - In this work the sequential and competitive coadsorption of IgG and BSA proteins
      on a sulfonate polystyrene latex with high surface charge density have been
      studied. For sequential coadsorption the IgG/a-CRP was first adsorbed and then
      the free surface of the particle was saturated by redispersion of the pellet in a
      solution with a high concentration of monomeric BSA (m-BSA). The competitive
      coadsorption experiments were carried out in two separate experiments by changing
      the initial concentration of one protein when the concentration of other protein
      was high and constant. During the incubation the pH was 5 or 6, and the ionic
      strength 2 mM, as in previous studies the adsorption of BSA was very low at
      neutral or basic pH regardless of the amount of adsorbed IgG. From these
      coadsorption experiments it was possible to obtain latex-protein complexes with a
      similar degree of coverage by each protein, high adsorption of IgG and different
      amounts of BSA, or high adsorption of BSA and a low, but significant, amount of
      IgG. The latex-protein complexes were electrokinetically characterized by
      measuring the electrophoretic mobility of each complex vs the pH of redispersion.
      In that way we can detect the i.e.p. of the complexes and the pH range in which
      the electrostatic repulsion can make them colloidally stable.

PMID- 7577827
TI  - Coadsorption of IgG and BSA onto sulfonated polystyrene latex: II. Colloidal
      stability and immunoreactivity.
AB  - The present work deals with the study of the colloidal stability and
      immunoreactivity of sulfonated polystyrene latex particles covered by different
      amounts of m-BSA and IgG/a-CRP. These proteins have been previously adsorbed onto
      a sulfonated latex by sequential and competitive coadsorption experiments and it
      was possible to obtain latex-protein particles with different degrees of coverage
      by each protein. The latex particles, fully or partially covered by each protein
      (termed latex-protein complexes), were resuspended under several conditions
      (different pH and ionic strength values) and their colloidal stability, vs the
      addition of the electrolyte was studied using turbidity measurements. This
      stability appeared at a high degree of coverage by BSA and at a pH in which the
      BSA was negatively charged. At a high degree of coverage by IgG, the latex
      particles were unstable at all pHs. As a final part of this work, the
      immunoreactivity of several complexes was studied following the changes in the
      turbidity after the addition of CRP antigen. Only the complexes which were
      colloidally stable gave detectable reactivity. However, the complexes with a
      relatively low degree of coverage by IgG/a-CRP gave good immunoreactivity.
      Therefore, the latex-protein complex properties depended on the percentage of BSA
      or IgG adsorbed and on the electric state of the proteins at the redispersion pH.
      Under specific incubation conditions, sulfonated latex covered by significant
      IgG/BSA percentages was obtained, which showed a high colloidal stability and
      good immunoreactivity.

PMID- 7577828
TI  - Cytoplasmic calcium level and membrane fluidity of platelets contacting
      poly(acrylamide-co-methacrylic acid) particles with different surface properties.
AB  - Changes in cytoplasmic free calcium levels and membrane fluidity of platelets in
      contact with poly(acrylamide-co-methacrylic acid) (PAAmMAc) particles were
      examined to analyze the mechanistic aspect of regulating platelet function. Our
      previous studies demonstrated interesting features of PAAmMAc particles during
      interaction with platelets: (1) PAAmMAc particles induce no calcium increase but
      enhance membrane fluidity of platelets: (2) thrombin induces no calcium increase
      in platelets when the platelets were mixed previously with PAAmMAc particles; and
      (3) PAAmMAc particles induce a calcium increase in platelets when they were
      treated previously with sodium azide (NaN3). These results suggest the
      possibility that PAAmMAc surfaces may regulate the calcium level by influencing
      platelet metabolism. In this study, non-cross-linked PAAmMAc solution with the
      same chemical composition as the particles showed a suppressive effect on
      thrombin-induced calcium increase, but, no influence on membrane fluidity. This
      result indicates that aggregated macromolecular surface assemblies of PAAmMAc may
      dominate the increase in membrane fluidity of platelets although the calcium
      change is induced by discrete molecular level interaction between the PAAmMAc and
      platelet membranes. It was also revealed that the suppression of thrombin-induced
      calcium increase and the membrane fluidity increase in platelets by PAAmMAc
      particles were reduced by albumin-treatment of the particles. This result
      suggests that such phenomena may be due to a decrease in any physicochemical
      interaction of PAAmMAc surfaces with albumin, rather than platelet metabolic
      change. PAAmMAc particle surfaces with higher carboxyl groups exhibited a more
      suppressive effect on thrombin-induced calcium increase, whereas those with lower
      carboxyl groups derived a higher calcium increase when the platelets were treated
      previously with NaN3. These results suggest the importance of electrostatic and
      any other physicochemical interaction of PAAmMAc chains on regulating cytoplasmic
      calcium levels.

PMID- 7577829
TI  - Silicone derivatives for contact lenses: functionalization, chemical
      characterization, and cell compatibility assessment.
AB  - Epoxy ring-opening functionalization of polymers at random sites along chains
      with various chemical groups has been demonstrated. The reaction is performed in
      an aqueous solution under mild conditions in order to minimize degradation of the
      macromolecular chains. Silicone lenses made of copolymers with epoxy side chains
      were functionalized with 4-hydroxybutyric acid, sodium salt. The carboxylated
      silicone derivatives were characterized by ESCA and radiotracers. A mean value of
      30% reaction yield was concluded, based upon data from both methods;
      nevertheless, the latter can be improved up to 50% or more if the conditions of
      preparation of the epoxydized silicone lenses are optimized. Derivatized
      silicones were coated in the wells of culture plates to evaluate the cell
      compatibility of these new polymers with a fibroblast cell line (McCoy's). No
      cellular toxicity was observed.

PMID- 7577830
TI  - Immobilization of heparin on polylactide for application to degradable
      biomaterials in contact with blood.
AB  - The poly-(D, L-lactide) RESOMER R208 (Boehringer-Ingelheim, Germany) was modified
      with heparin to improve the blood contacting properties of the material. The
      immobilization of herapin was carried out by covalent binding with glutaraldehyde
      as the coupling agent. The reaction conditions, such as temperature and time,
      were varied to optimize the binding of heparin. The efficiency of the
      immobilization was monitored with respect to the total amount of coupled herapin
      with a toluidine blue assay and the anticoagulant activity of immobilized heparin
      with a factor Xa assay. The hemocompatibility of the modified polylactide was
      estimated after blood-material contact by the activation of platelets measured
      with an enzyme immuno assay for GMP140. Immobilization at ambient temperature and
      a reaction time of 2 h resulted in maximal heparin binding, high anticoagulant
      activity, and low thrombogenicity. Since the remaining unsaturated aldehyde
      groups of the coupling agent may cause a low hemocompatibility of the material,
      washing of the heparinized polylactide was carried out with ethanol. However, it
      was shown that washing diminished the anticoagulant activity of heparin and
      increased the thrombogenicity. The prolonged storage of heparinized polylactide
      in phosphate buffered saline for 8 days demonstrated that small quantities of
      heparin were released but the hemocompatibility was further improved, indicated
      by an increasing anticoagulant potential and a decrease in platelet activation
      with incubation time. A comparison of polylactide, heparinized polylactide,
      polypropylene, and Pellethane with respect to platelet activation by GMP140 assay
      and scanning electron microscopy, revealed that the heparinization of polylactide
      substantially improved the hemocompatibility of RESOMER R208, making the material
      comparable to Pellethane.

PMID- 7577831
TI  - Polyethylene glycol-modified avidin: a novel agent for the selective extraction
      of biotinylated immune-complex in an aqueous two-phase system.
AB  - Chicken avidin was chemically modified with 2,4-bis[O-methoxypoly(ethylene
      glycol)]-6-chloro-s-triazine (activated PEG2) to form PEG-avidin. The PEG-avidin,
      in which 78% of the amino groups were modified, retained 49% of the active biotin
      binding sites. The modified avidin was partitioned preferentially into the PEG
      phase in an aqueous two-phase system (PEG/dextran). Using PEG-avidin, the immune
      complex formed between biotinylated anti-mouse IgG and its antigen IgG (mouse)
      molecules, was successfully transferred into the PEG-phase in an aqueous two
      phase system. This finding leads to the effective isolation of a specific antigen
      among various kinds of antigens by partitioning with a two-phase system using PEG
      avidin.

PMID- 7577832
TI  - Fibroblast spreading and proliferation on hydrophilic and hydrophobic surfaces is
      related to tyrosine phosphorylation in focal contacts.
AB  - Fibroblasts adhesion, spreading, and proliferation was investigated in this study
      using glass and octadecyl glass (ODS) as models for hydrophobic substrata in the
      absence or presence of preadsorbed fibronectin (FN). To learn more about the
      underlying mechanism of the biocompatibility of materials, the organization of
      the beta 1 integrin and the phosphorylation of tyrosine residues in focal
      contacts was investigated by immunofluorescence microscopy. The diminished
      adhesion and spreading of fibroblasts on hydrophobic ODS in comparison to clean
      glass was indicated by a diffuse presence of actin and by the absence of focal
      contacts and phosphotyrosine activity. In contrast, on hydrophilic glass, initial
      stress fibres and focal adhesions appeared accompanied by a moderate
      phosphotyrosine activity. The preadsorption of FN improved the interaction of
      fibroblast with both surfaces as indicated by the formation of prominent actin
      stress fibres and the clusterization of beta 1 integrins in the focal contacts
      which was co-localized with an increased phosphotyrosine activity. The
      proliferation of fibroblasts measured after 72 h was inhibited on ODS in
      comparison to glass. Preadsorption of FN, however, increased the cell
      proliferation index on both surfaces, which was higher than on pure glass. The
      improved cell adhesion, spreading, and proliferation of fibroblasts run in
      parallel with an increased total tyrosine phosphorylation activity measured by an
      enzyme immuno assay (EIA). It was concluded that the signalling via integrins
      might be a decisive event during the cell-biomaterial interaction.

PMID- 7577834
TI  - Flow cytometric analysis of pig epidermal keratinocytes: effects of ultraviolet B
      irradiation (UVB) and topical PUVA treatment.
AB  - The effects of a single application of ultraviolet B irradiation (UVB) and
      topical PUVA treatment on pig epidermal cell kinetics were studied by DNA-flow
      cytometry (FCM), 3H-thymidine uptake, mitotic counts and 2-3H-deoxy-D-glucose
      uptake. Following UVB irradiation (2MED: 250 mJ/cm2) and PUVA (0.9, 1.4 J/cm2)
      treatment, thymidine uptake and mitosis were markedly decreased. This was
      followed by a transient increase in all of these parameters. The maximal increase
      was observed at 96 h following the UVB irradiation and at 168 h following the
      PUVA treatment (0.9 J/cm2), respectively. The suppression of DNA synthesis and
      mitosis persisted for a longer period in PUVA-treated than in UVB-treated
      epidermis. At 48-72 h after the UVB irradiation and 72-144 h after the PUVA
      treatment, an increase in the cells of the G2/M fraction was observed. This was
      associated with the decreased mitotic counts, suggesting accumulation of G2
      blocked cells. Histologically, PUVA-treated epidermis showed a considerable
      degenerative change. Mild acanthosis was noted at 72-96 h in UVB-treated
      epidermis and at 168 h in PUVA-treated epidermis. These results indicate that the
      inhibition of DNA synthesis and increase in G2-phase cells are associated with
      the UVB and PUVA induced suppression of epidermal cell proliferation. These
      suppressive effects that persisted longer in PUVA-treated, than in UVB-treated
      epidermis, were followed by an increased epidermal keratinocyte proliferation of
      pig skin in vivo.

PMID- 7577833
TI  - Influence of free residual chlorine on cultured human epidermal keratinocytes
      from normal skin and hypertrophic scars.
AB  - In Japan, public health regulations state that the water in rinsing pools used
      before swimming should contain 50-100 mg/l of chlorine. We examined the influence
      of chlorination at high concentrations in rinsing pools on the skin using
      cultured human epidermal keratinocytes from normal skin and hypertrophic scars.
      Chlorination of cell culture for 15 min with 200 mg/l of free residual chlorine
      proved cytotoxic to both types of keratinocytes as did 100 mg/l of free residual
      chlorine for 1 or 3 consecutive days. Keratinocytes from hypertrophic scars, when
      cultivated in 100 mg/l of free residual chlorine, were more vulnerable to
      chlorine than those from normal skin. Cell characteristics of cultured
      keratinocytes from hypertrophic scars may be somewhat different from those of
      normal skin. The phenomena observed in this experimental model of the skin
      suggest that people exposed to chlorine in rinsing pools at concentrations in
      excess of 200 mg/l for about 15 min before swimming are at risk of developing
      cutaneous disorders, especially at sites of injury, e.g. scars.

PMID- 7577835
TI  - Protective activity of hamamelitannin on cell damage of murine skin fibroblasts
      induced by UVB irradiation.
AB  - The protective activities of hamamelitannin (2',5-di-O-galloyl-hamamelose) in
      Hamamelis virginiana L. and its related compound, gallic acid, on damaged murine
      skin fibroblasts induced by UVB irradiation were investigated. In order to
      exclude the UV absorbing effect of the compounds, the protection study was
      performed such that the fibroblasts were pretreated with hamamelitannin or gallic
      acid for 24 h before UVB irradiation. At 200 microM concentration, hamamelitannin
      gave the higher survival of 72.6 +/- 0.4% in comparison with that of gallic acid
      (35.5 +/- 1.0%), while UVB absorbers such as 2-ethylhexyl p-methoxycinnamate and
      hexylbenzoate did not show such protection. The scavenging activities of
      hamamelitannin and gallic acid against active oxygens such as superoxide anion
      radicals, hydroxyl radicals and singlet oxygens were evaluated using electron
      spin resonance (ESR-spin trapping method). Hamamelitannin and gallic acid showed
      potent scavenging activities against all active oxygens tested. Furthermore, the
      association of hamamelitannin to fibroblasts was examined by comparing it with
      that of gallic acid, and the following results were obtained: (1) hamamelitannin
      reduces the reaction rate of liposome entrapped-nitroblue tetrazolium (NBT) with
      external superoxide anions, and (2) several glycosides associate with
      fibroblasts. From these results, it was concluded that hamamelitannin protects
      murine fibroblasts against external active oxygens by associating with the cell
      surface through its sugar moiety.

PMID- 7577838
TI  - Immunohistochemical demonstration of non-muscle myosin in the developing porcine
      epidermis.
AB  - Using an immunohistochemical technique, the study demonstrates for the first time
      non-muscle myosin stress fibres in fetal mammalian epidermis, with special regard
      to cellular development during integumentary ontogenesis in the sparsely haired
      domesticated pig. The results obtained are discussed in view of possible
      cytoskeletal functions of the cytofilaments.

PMID- 7577836
TI  - Histopathological and capillaroscopical features of the cuticles and bleeding
      clots in ring or middle fingers of systemic scleroderma patients.
AB  - Sixty-three patients with systemic scleroderma (SSc) (Barnett I, 41; Barnett II,
      17; Barnett III, 5), 14 with systemic lupus erythematosus (SLE), 9 with
      dermatomyositis (DM) and 10 healthy controls (HC) were subjected to
      histopathological examinations of the cuticles of ring or middle fingers. The sex
      ratios (male/female) in the patients with SSc, SLE, DM and HC were 7:56, 5:9, 5:4
      and 5:5, and the ages were 22-74, 19-78, 45-70 and 13-78 years old, respectively.
      Biopsy samples were taken from the central portion of the cuticles, which showed
      the most severe change of elongation with or without bleeding clots of cuticle
      proximal nailfolds (BC). Histopathologically, 61 (96.8%) cuticles of SSc patients
      consisted of the upper (U), middle (M) and lower (L) layers, which represent
      obliquely stacked, parabolic, and parallel stacked layers, respectively. The
      middle parabolic layer appeared to discharge homogenous eosinophilic globular
      deposits (ED). On the other hand, this typical three-layer-nail pattern was seen
      only in 9 (64.3%) of SLE, 3 (33.3%) of DM and none of HC, in total 12 (36.4%) of
      the non-SSc group, which included SLE, DM and HC. In SSc, there were statistical
      correlations (R2) between ED and BC, ED and cuticle-elongation, cuticle-layer and
      cuticle-elongation, ED and cuticle-layer, BC and cuticle-elongation.
      Capillaroscopically, bleeding clots located in the middle layer with ED of the
      cuticles in eight patients with SSc were transported rapidly within 1-2
      weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577837
TI  - The enhancement of cellular infiltration and vascularisation of a collagenous
      dermal implant in the rat by platelet-derived growth factor BB.
AB  - The implantation of collagen-based dermal substitutes offers one means of
      management of full-thickness skin lesions. We have examined the effect of the
      recombinant BB homodimer of platelet-derived growth factor (rPDGF-BB) on the
      extent of cellular infiltration and vascularisation of collagen sponges implanted
      into full-thickness excision wounds in rats. Histological examination of sponges
      excised 14 and 21 days post-implantation in dose-response studies in which 0-4
      micrograms rPDGF-BB were applied to the undersurface of each sponge, immediately
      prior to its implantation, demonstrated a progressively increased infiltration of
      host cells, especially fibroblasts, and enhanced capillary formation. With 4
      micrograms rPDGF-BB, an enhanced infiltration of fibroblasts into sponges was
      already apparent 3 days post-implantation, and enhanced capillary formation was
      noticeable after 7 days. This neovascularisation was noted to be associated with
      improved survival of autologous split-thickness skin grafts applied to the
      sponges immediately following their implantation.

PMID- 7577839
TI  - Increased spontaneous production of IL-8 in peripheral blood monocytes from the
      psoriatic patient: relation to focal infection and response to treatments.
AB  - To evaluate the contribution of peripheral blood monocytes (PBMC) to
      epidermotropic inflammatory reactions in psoriasis, using an enzyme-linked
      immunosorbent assay we measured spontaneous interleukin-8 (IL-8) production in
      PBMC obtained from patients with psoriasis. IL-8 production in the psoriatic PBMC
      was significantly higher than that in normal control PBMC. Plasma IL-8 levels in
      psoriatic patients were also moderately increased compared to normal control
      levels. IL-8 production in PBMC was closely related to the clinical severity of
      psoriasis and to the response to treatment, including systemic methotrexate (MTX)
      treatment and tonsillectomy. IL-8 production in PBMC was also positively related
      to the production of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha) in these cells. We speculate that the
      chemotactic cytokine IL-8 contributes to the development of psoriatic skin
      lesions, and mediates inflammatory reactions from the inflammatory focus to the
      psoriatic lesions.

PMID- 7577840
TI  - Representing and understanding geometric features of one-dimensional tunnel
      structures in solid inclusion compounds.
AB  - A computational method is presented for probing geometric, topological, and
      structural characteristics of one-dimensional tunnel structures in solid
      inclusion compounds. The method is illustrated for the urea and thiourea
      inclusion compounds, highlighting important structural differences between the
      urea and thiourea tunnel structures, and potential areas of application of the
      methodology are discussed.

PMID- 7577842
TI  - Annotating PDB files with scene information.
AB  - We have implemented extensions to the Brookhaven Protein Data Bank (PDB) file
      format for incorporating scene information such as viewing parameters, additional
      molecular information (e.g., van der Waals radii and atom colors), and user
      defined graphics. These extensions were made in conformance with the PDB standard
      and provide sufficient information to render the scene in various styles such as
      space-filling images and ribbon diagrams. For the past 5 years these extensions
      have been used in the MidasPlus molecular modeling system and have proved both
      powerful and sufficient for generating complex molecular images. We propose that
      the extensions to the PDB presented here be adopted by the molecular modeling
      community for incorporation into visualization programs.

PMID- 7577843
TI  - Systematic representation of protein folding patterns.
AB  - A tabular representation of protein folding patterns is described, which
      comprises information about the order along the chain of helices and strands of
      sheet, identifies the elements of secondary structure that interact, and
      indicates their relative orientation. These tableaux are intelligible to both
      people and computers, and support the application of algorithms for
      identification of proteins with similar folding patterns. Their inclusion in a
      database of protein structures would support investigations of structural
      relationships at the topological level.

PMID- 7577841
TI  - Methods for displaying macromolecular structural uncertainty: application to the
      globins.
AB  - Most molecular graphics programs ignore any uncertainty in the atomic coordinates
      being displayed. Structures are displayed in terms of perfect points, spheres,
      and lines with no uncertainty. However, all experimental methods for defining
      structures, and many methods for predicting and comparing structures, associate
      uncertainties with each atomic coordinate. We have developed graphical
      representations that highlight these uncertainties. These representations are
      encapsulated in a new interactive display program, PROTEAND. PROTEAND represents
      structural uncertainty in three ways: (1) The traditional way: The program shows
      a collection of structures as superposed and overlapped stick-figure models. (2)
      Ellipsoids: At each atom position, the program shows an ellipsoid derived from a
      three-dimensional Gaussian model of uncertainty. This probabilistic model
      provides additional information about the relationship between atoms that can be
      displayed as a correlation matrix. (3) Rigid-body volumes: Using clouds of dots,
      the program can show the range of rigid-body motion of selected substructures,
      such as individual alpha helices. We illustrate the utility of these display
      modalities by the applying PROTEAND to the globin family of proteins, and show
      that certain types of structural variation are best illustrated with different
      methods of display.

PMID- 7577845
TI  - Feed-forward neural networks for secondary structure prediction.
AB  - A feed-forward neural network has been employed for protein secondary structure
      prediction. Attempts were made to improve on previous prediction accuracies using
      a hierarchical mixture of experts (HME). In this method input data are clustered
      and used to train a series of different networks. Application of an HME to the
      prediction of protein secondary structure is shown to provide no advantages over
      a single network. We have also tried various new input representations, chosen to
      incorporate the effect of residues a long distance away in the one-dimensional
      amino acid chain. Prediction accuracy using these methods is comparable to that
      achieved by other neural networks.

PMID- 7577844
TI  - Molecular surface comparison. 2. Similarity of electrostatic vector fields in
      drug design.
AB  - In the first article of this series a real-time graphics method was described for
      molecular similarity of scalar properties. This has now been extended for the
      comparison of molecular vector properties, most notably electrostatic field. A
      comparison of the various techniques of calculating fields is presented that
      includes a new method based on natural orbital fitted point charges. In the two
      examples described, namely, a series of benzodiazepine agonists and a set of
      serotonin 5-HT3 antagonists, the program has been shown to produce useful
      pharmacophoric overlaps that can be used in the design of novel therapeutic
      agents.

PMID- 7577846
TI  - MOLGEN: personal computer-based modeling system.
AB  - MOLGEN is a comprehensive molecular modeling package that runs on personal
      computers and allows building, drawing, storing, and comparison of molecular
      structures. The system contains modules for geometry optimization and
      conformational analysis, and modules for calculation and description of
      lipophilicity and electrostatic potentials and for their three-dimensional
      matching based on gnomonic projection. Described here are a systematic
      conformation search running on PCs and a new approach to 3D similarity analysis
      of lipophilic potentials. The drug design applicability of the program is further
      enhanced by database facilities for retrieving and storing any structure data
      sets. The program features and examples of its applications are presented.

PMID- 7577847
TI  - Discriminating D1 and D2 agonists with a hydrophobic similarity index.
AB  - Currently, methods for calculating molecular similarity indices have been
      developed for comparing steric, charge density, and molecular electrostatic
      potential (MEP) properties. Much of the existing technology may, however, be
      applied to the quantitative comparison of molecular hydrophobicities. In this
      article we present an empirical hydrophobic similarity index. We utilize atomic
      hydrophobic parameters derived from a quantum mechanical semiempirical
      wavefunction. Hydrophobicity at points on a grid is computed with a recently
      introduced "molecular lipophilicity potential." The overlap of pairs of molecules
      is calculated with the metric introduced by Carbo. This approach is applied to a
      case in which steric and electrostatic criteria have already been shown to be
      inadequate in rationalizing selectivity, namely, requirements for recognition at
      the dopamine D1 and D2 receptors. We demonstrate that, for a set of dopamine
      agonists, D1 ligands show higher similarity in this property that D2 analogs.
      This indicator of similarity is more successful at accounting for D1 selectivity
      than previous methods.

PMID- 7577848
TI  - ANTHEPROT 2.0: a three-dimensional module fully coupled with protein sequence
      analysis methods.
AB  - ANTHEPROT is a fully interactive graphics program devoted to the analysis of the
      sequences and structures of proteins. This program, originally developed to
      facilitate the protein sequence analysis coupled with multiple alignments and
      predicted secondary structures of proteins, now comprises a powerful 3D module to
      display and handle macromolecular structures. All the methods that were
      previously integrated into ANTHEPROT are now directly coupled with a 3D window
      that provides the user all the classic features of a molecular modeling package.
      Indeed, it allows real-time rotation and translation of 3D structures with many
      kinds of models in depth-cueing mode (space filling, backbone, wire models, main
      chain, and ribbons), selections (atom type, residue type, segments, and chain),
      color-coding systems (amino acid properties, predicted or observed secondary
      structures, temperature B factor, and subunits), geometric calculations
      (Ramachandran plot, distances, and angles), and fitting molecules. Stereo views
      are possible as well as HPGL standard files. A module specifically devoted to the
      determination of 3D structures using nuclear magnetic resonance is also
      available. This major release of our program for IBM rs6000 workstations is
      available by anonymous ftp to ibcp.fr for academic institutions.

PMID- 7577849
TI  - Updating the clinical experience in endometriosis--the European perspective.
AB  - In a large, double-blind, multicentre study, 269 patients with confirmed
      endometriosis were randomly allocated to receive either danazol (200 mg twice
      daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The
      two groups were comparable in terms of the staging of endometriosis by the
      American Fertility Society (1979) score. After the sixth month of treatment,
      repeat laparoscopy was performed. Clinical assessment, haematological and
      biochemical investigations were carried out during the 6 months of treatment and
      for a further 12 months' follow-up and are compared between the two groups. A
      total of 15 patients from the gestrinone group, including four patients with
      hirsutism, and 17 patients from the danazol group, including six patients with
      headache, withdrew because of adverse symptoms. An additional 22 patients,
      including 10 from the gestrinone group and 12 from the danazol group withdrew
      because of lack of efficacy, pregnancy, elevated hepatic function tests or for
      reasons unrelated to the trial. Total American Fertility Society scoring showed
      an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99
      patients receiving danazol. The results showed a significant reduction in the
      severity of dysmenorrhoea by the third month in the danazol group and at 6 months
      in both groups. There was a significant (P < 0.001) increase in weight observed
      in both groups during treatment. Overall, the tolerability of danazol and
      gestrinone was good; however, significantly more patients with gestrinone
      complained of hirsutism while significantly more with danazol complained of leg
      cramps. During the 12 months of follow-up, mild, moderate or severe degrees of
      lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no
      statistically significant increase in frequency in either group.

PMID- 7577850
TI  - Updating the clinical experience in endometriosis--the Brazilian perspective.
AB  - In an open-label, multicentre, randomized, parallel group study, 164 women with
      endometriosis were assigned to treatment. Out of these women, 81 received danazol
      (600 mg daily for 8 weeks, then 400 mg for 16 weeks) and 83 were given gestrinone
      (2.5 mg twice a week for 24 weeks). Five weeks before the start of treatment
      clinical evaluation and diagnostic laparoscopy were performed during the
      screening visit. Drug assignment and laboratory data assessment were carried out
      within 3 days of the estimated onset of the menstrual cycle at baseline visit.
      The response to treatment was assessed during visits at weeks 2, 4, 8, 12, 16, 20
      and 24; at the last visit a second laparoscopy was performed. Therapeutic
      efficacy was evaluated by analysis of the laparoscopic scores assessed according
      to the revised American Fertility Society classification. Symptomatic response
      was measured by clinical scores and laboratory data. In one centre, bone mineral
      density was also recorded. One patient in the danazol group discontinued
      treatment due to a cutaneous rash as a probable adverse reaction at the beginning
      of the study. The therapeutic efficacy of danazol and gestrinone did not differ
      significantly when the revised American Fertility Society scores were compared.
      The symptomatic response also showed no statistical difference when clinical
      examination scores were analysed. There was no significant difference between the
      drugs in laboratory data, including bone mineral density, with respect to adverse
      events. Analysis of clinical scores showed that danazol was superior to
      gestrinone with respect to acne and irregular bleeding. Based on these data, we
      conclude that both danazol and gestrinone are reliable in the treatment of
      endometriosis and offer similar results.

PMID- 7577851
TI  - Pain and infertility--a rationale for different treatment approaches.
AB  - Endometriosis may result in pain and/or infertility in some patients, while
      others may remain asymptomatic. The disease appears to progress and regress
      somewhat unpredictably, making it difficult to determine the appropriate
      treatment. Progression of the disease can be altered by medical and surgical
      treatments used according to general guidelines but selected for the individual.
      Coagulation, medical suppression and observation are frequently the first
      approaches to infertility or pain resulting from endometriosis. Deep dissection
      and excision may be indicated with deep disease, persistent pain or persistent
      tenderness.

PMID- 7577854
TI  - Peritoneal pseudocyst--ventriculo-peritoneal shunt complications.
AB  - Pseudocyst formation is a rare complication of ventriculo-peritoneal shunt,
      occurring in only 22 cases of 1300 shunts from 1968 to 1992. The most common
      presentation is that of abdominal signs rather than neurological or infectious
      signs. The diagnosis is easy with ultrasonography. The difficulty is to evocate
      the cyst and to correlate symptoms and cyst. Treatment of the cyst was by
      aspiration (21 cases) and excision in 7 cases. The therapeutic choice is made
      according to the ultrasound findings. When the cyst was infected, an external
      ventricular shunt was used temporary, but this type of shunt must be avoided
      where possible. Three patients died.

PMID- 7577852
TI  - Immune dysfunction--a potential target for treatment in endometriosis.
AB  - The treatment approach towards endometriosis has been traditionally either
      surgical or hormonal in nature. Since endometriosis is, to a large extent, a
      microscopic disease, a surgical approach cannot be expected to eradicate the
      disease. Treatment is, therefore, generally attempted by hormonal manipulation,
      an approach based on the known oestrogen sensitivity of endometriosis. Hormonal
      manipulation can only temporarily affect endometriosis, and quite clearly does
      not address the underlying aetiology and/or pathophysiology of the disease. Since
      neither is, at present, well understood, one can only speculate as to the
      treatment approach that would, in fact, affect the pathophysiology of the
      condition. Endometriosis has, in recent years, been characterized by a large
      number of immunological abnormalities in the host. It is, therefore, very
      tempting to speculate that an immunological defect represents the basic
      abnormality which later leads to the occurrence of the disease. This assumption
      is supported by the observation that those immunological defects are already
      present in the mildest forms of the disease. In fact, if one believes that many
      cases of unexplained infertility represent undiagnosed microscopic endometriosis,
      then evidence suggests that this precursor stage of the disease is basically
      characterized by an identical immunological profile to that of endometriosis. An
      immunological aetiology and/or pathophysiology of endometriosis should lead to an
      immunological treatment approach toward the disease. Specifically, a number of
      non-specific immunomodulators, presently utilized in a variety of medical
      conditions with immunological aetiologies, would seem to represent promising new
      therapeutic strategies to conquer endometriosis at its roots. A new treatment
      approach to endometriosis appears urgently needed since, at least with regard to
      the effects of endometriosis on fertility and pregnancy loss, present approaches
      have proven ineffective.

PMID- 7577853
TI  - Histological impact of medical therapy--clinical implications.
AB  - The medium- and long-term effects of gestrinone and danazol on the endometrium
      were examined in 36 patients with endometriosis. Endometrial biopsies were taken
      from each patient before treatment and after 3 and 6 months of treatment with 600
      mg danazol daily (n = 17) or with 2.5 mg gestrinone twice weekly (n = 19).
      Endometrial samples were analysed by light, scanning and transmission electron
      microscopy. At 3 months' treatment the endometria of patients treated with
      danazol appeared more atrophic than those of the women treated with gestrinone;
      some cell organelle involution was evident in all patients. After 6 months of
      treatment a marked atrophy was observed in patients of both treatment groups. A
      complete involution of cytoplasmic organelles with cytoplasmic collapse and a
      shift of nucleoplasmic ratio in favour of the nucleus occurred in patients
      treated with danazol; the cytoplasmic organelle involution was less marked in
      patients treated with gestrinone. Compared with gestrinone, danazol induces more
      rapid endometrial atrophy, with greater impairment of the cytoplasm and cell
      secretory activity.

PMID- 7577855
TI  - Neural tube defects: an experimental model in the foetal rat.
AB  - We report on our experience in the experimental induction of Neural Tube Defects
      (NTD) in the foetal rat by maternal administration of retinoic acid. The
      teratogen diluted in olive oil was administered in a single intragastric dose
      (125 mg/kg body weight) to pregnant rats (n = 31) on the 10th day of gestation.
      Pure olive oil was given to control rats (n = 9). The foetuses were recovered by
      caesarian section on the 20th day and prepared for morphological investigation.
      We have studied 201 experimental and 82 control animals. There were NTD in 36.3%
      of experimental foetuses and none in the control ones. Sacral dysraphism was the
      most frequent defect but we also observed Arnold Chiari malformations and
      crowding of the bony limits by an enlarged neural axis. Other associated
      malformations found were: craneofacial (78.1%), caudal (80%), anorectal (31.4%),
      and limb defects (89.5%). This simple and inexpensive model may allow us to gain
      a better knowledge of the biology in the foetus with NTD.

PMID- 7577856
TI  - Gastroesophageal reflux in association with the Sandifer syndrome.
AB  - Eight children presenting with the Sandifer syndrome (with neck contorsion,
      radiologic studies of the cervical spine and normal neurologic exploration) have
      been studied in relation to gastro-esophageal reflux (GER). In the eight cases
      barium swallow, 24 h pH-metering, manometry, endoscopy and biopsy were made,
      presenting pathological GER. The barium swallow was pathologic in 62% of them.
      The pH-metering in 37%. The lower esophageal sphincter pressures were decreased
      in 37%, with esophageal motility alteration in 75%. Signs of macro and/or
      microscopic esophagitis were found in 62%. Three patients received surgical
      treatment and the rest medical treatment, with improvement of the neck contorsion
      in all cases. We have attempted to evaluate which one of the functional
      explorations for the GER diagnosis is better in this kind of patients, and we
      have demonstrated that the most frequently found alteration is the esophageal
      dysmotility.

PMID- 7577858
TI  - TIPS: a new therapy for esophageal variceal bleeding caused by EHBA.
AB  - Clinical and procedural experience using transjugylar intrahepatic portosystemic
      shunt (TIPS) on 7 children with recurrent hemorrhage of esophageal varices is
      reported. Recurrent hemorrhage from esophageal varices following repeated
      paravasal sclerosing of the varices as well as severe-grade hypersplenism are
      proposed as the indication for its use. The technical details of TIPS, observed
      and possible early and late complications, the demand for a decrease in the
      portosystemic pressure gradient to less than 15 mmHg and the influence of TIPS on
      improvement of the varices, hypersplenism and the frequently observed
      malabsorption are described.

PMID- 7577857
TI  - Long-term functional results and quality of life after colon interposition for
      long-gap oesophageal atresia.
AB  - Out of a series of 146 patients with oesophageal atresia 9 (6.2%) underwent colon
      interposition from 1963 to 1971. All eight surviving patients were seen at follow
      up after a mean of 22 years. Three patients were free of specific symptoms
      according to the criteria of DeMeester, two had moderate and three severe
      distress. The mean time for consuming a standardized test meal was 15 minutes,
      compared to 8 minutes in healthy controls. Patients required 1-9 minutes to
      transport liquid barium through the transplant, compared to < 10 seconds in
      control subjects. Histological evaluation revealed a normal architecture of the
      colonic and ileal epithelium in three patients who underwent endoscopy. In none
      of these patients were contractions in the colon graft related to the act of
      swallowing recorded on manometry. Unimpaired quality of life was indicated by the
      Spitzer index which scored a mean of nine out of ten points. However, on a
      100point visual analogue scale patients scored their global quality of life 66
      and the mean Gastrointestinal Quality of Life Index was 92.2, compared to 107.6
      in healthy control subjects (p < 0.05). This impairment was exclusively due to
      specific symptoms which scored 49.3 in patients and 59 in healthy individuals (p
      < 0.05). Physical and social functions, emotions, and inconvenience of a medical
      treatment were similar to control subjects. We conclude that colon interposition
      for long-gap oesophageal atresia achieves acceptable long-term functional
      results. However, specific symptoms lead to a considerable impairment in quality
      of life.

PMID- 7577859
TI  - Fertility rates after successful correction of varicocele in adolescence and
      adulthood.
AB  - Vast epidemiologic studies have shown that varicocele becomes manifest at the
      beginning of sexual maturation and its incidence gradually increases in patients
      between 10-16 years. This percentage is 16-18% in adolescents and is comparable
      to that of the adult male population. Since varicocele first appears in early
      adolescence and its gonadotoxic effect increases with age, the possibility of
      improved fertility rate with early varicocelectomy has been suggested. We report
      the results of a comparative follow-up study to value the efficacy of surgical
      correction in two groups of adolescent and adult patients. Our study shows that
      early recognition and treatment of a severe varicocele provide a higher fertility
      rate and can prevent the reduced fertility rate associated with delayed
      varicocelectomy.

PMID- 7577860
TI  - Adolescent varicocele: operative anatomy and tricks for successful correction.
AB  - Conventional varicocelectomy is often complicated by high recurrence rate,
      ranging from 6 to 25% and the persistence usually is due to residual venous
      communications. We report our experience of 21 years in varicocele correction
      using 3 different operative techniques on 389 adolescents. In the first 12 years
      (120 patients) a typical ivanissevich operation was carried out with a recurrence
      rate of 18%. In the following 4 years (63 patients) a preoperative venography was
      always carried out and a surgical procedure via an inguinal approach was
      performed with high retroperitoneal and inguinal ligations of the internal
      spermatic vein(s) and cremasteric vein(s) as indicated by venography; the
      recurrence rate was still 8%. In the last 5 years we have been using a personally
      modified technique characterized by: 1) unique access to all venous areas both in
      the retroperitoneum and in the inguinal canal with a systematic ligation of the
      internal and external spermatic veins and the deferential vein when dilated; 2)
      intraoperative identification of the residual collaterals after venous ligations
      by injecting some milliliters of a blue-methylene solution. This procedure
      allowed a varicocele recurrence in only 2 out of 206 consecutive patients (1%).
      Our results suggest that it may be possible to lessen significantly the
      postoperative recurrence rate using some simple operative tricks.

PMID- 7577861
TI  - Peno-scrotal transposition.
AB  - Peno-scrotal transposition is an infrequent genital malposition due to a defect
      in the caudal migration of the inchoate scrotum during intrauterine life. It is
      frequently associated with urogenital and/or gastrointestinal malformations.
      Glenn and Anderson (1973) have classified the abnormality into the following
      categories, according to severity: Bifid scrotum Incomplete or partial peno
      scrotal transposition Complete peno-scrotal transposition or pre-penile scrotum
      Ectopic scrotum We analyse corrective surgical techniques for this malposition
      and we present our experience.

PMID- 7577862
TI  - Growth hormone effects on wound healing in malnourished animals: a histological
      study.
AB  - Systemic growth hormone (GH) markedly improves celiotomy wound strength in
      protein malnourished (PM) animals. This study was undertaken to analyze the
      effect of GH as a basis for anatomically understanding. Adult female Spraque
      Dawley rats were divided into normally nourished controls, PM and GH-treated PM
      groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow
      every other day for eight weeks before surgery. Controls were fed 23.4% protein
      chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was
      injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five
      days after 5 cm midline celiotomy. Bursting strength of the wound was measured at
      3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and
      eosin) were obtained from each group. Wound strength of malnourished rats was
      significantly less than that of normal controls at six days after operation (p <
      0.001). With administration of growth hormone, the wound strength was
      significantly improved. Histologically, there was no difference between groups on
      day 3. On day 6 the normal control group showed a decrease in the early
      inflammatory cell infiltrate with concurrent development of granulation tissue
      and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration,
      a very narrow band of poorly formed granulation tissue and a sparse fibroblastic
      proliferation. The GH-treated PM group showed a combination of histologic
      findings. Fatty infiltration, similar to that in malnourished non-treated
      animals, was still evident but there was also a dense proliferation of capillary
      channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577863
TI  - New biofeedback therapy in children with encopresis.
AB  - Biofeedback therapy was performed in 13 patients with encopresis using newly
      devised computerized equipment. The patients were children, aged 6 to 11 years,
      who had not responded to trials of conventional therapy with a mean follow-up
      period of three years and two months. The biofeedback therapy was effective in 12
      of the 13 patients after one course of therapy. This positive results was
      attributed to the computerized equipment. The patients could more easily
      recognize how to squeeze their anal sphincters after seeing a colored ellipse
      representing sphincter pressure on a monitor. The results of anorectal manometry
      and electromyography (EMG) showed that biofeedback therapy improved the voluntary
      sphincter function and rectal sensation. Therefore, biofeedback therapy might be
      effective in patients with encopresis whose sphincter functions are intact.

PMID- 7577864
TI  - Extra-lobar pulmonary sequestration with prenatal diagnosis. A report of 5 cases
      and review of the literature.
AB  - THE PURPOSE of this work was to study the pre- and postnatal features of extra
      lobar pulmonary sequestration (ELPS) and consider their diagnosis and treatment.
      METHODS: Five ELPS diagnosed prenatally (1986-1992) were reviewed
      retrospectively. RESULTS: In 2 cases, prenatal diagnosis was based on the
      presence of a left suprarenal mass for which tumor markers proved negative
      postnatally. These 2 infants underwent surgery at 3 weeks of age for supposed
      neuroblastoma or teratoma. In the other 3 cases, diagnosis was based on the
      presence of a solid mass at the left base of the thorax. The systemic vessel was
      visualized in 2 of these cases; mediastinal displacement was noted in one case
      and hydrothorax (which recurred after puncture) in the other. The latter infant
      was born at 34 weeks of amenorrhea, and hydrothorax disappeared postnatally after
      excision of the ELPS. The other two infants were asymptomatic at birth and
      underwent surgery respectively on the 8th day and during the 6th month of life.
      CONCLUSION: ELPS can take the form of a mass in the abdomen or at the base of the
      thorax. For subdiaphragmatic ELPS, surgical excision (possibly preceded by
      percutaneous puncture) is required if the diagnosis is uncertain.
      Supradiaphragmatic ELPS can be complicated prenatally by hydrothorax or even
      hydrops, requiring drainage in utero. If the infant is asymptomatic postnatally,
      systematic surgical excision should be considered. Extra-lobar pulmonary
      sequestrations (ELPS) are masses of nonfunctional lung tissue vascularized by an
      abnormal systemic artery and covered with a pleural layer isolating them from the
      rest of the parenchyma. The diagnosis of these malformations is based
      increasingly on obstetrical ultrasonography. The purpose of this study was to
      specify the prenatal features of these malformations and define the diagnostic
      approach and therapeutic strategy.

PMID- 7577865
TI  - Traumatic rupture of mesenteric cyst: a life-threatening complication of a rare
      lesion.
AB  - Mesenteric cysts are very rare. Most of the cases are asymptomatic except when
      complicated. A mesenteric cyst ruptured due to trauma in a 3-year-old boy is
      described. It was diagnosed intraoperatively and treated surgically.

PMID- 7577866
TI  - Intestinal atresia following intraamniotic use of dyes.
AB  - Since 1990 avoidance of methylene blue as a dye in diagnostic amniocentesis is
      recommended. This is a result of the observation that a high incidence of
      jejunoileal atresia appeared in twin pregnancies following intraamniotic
      injection of methylene blue. We report four further cases of jejunoileal atresia
      in twins after intraamniotic injection of dyes since 1991. We describe the
      clinical course, discuss possible teratogenic mechanisms and emphasize again that
      synthetic dyes should not be used in second trimester amniocentesis.

PMID- 7577868
TI  - Juvenile xanthogranuloma of the pelvic origin: a case report.
AB  - A case of juvenile xanthogranuloma (JXG) originating from the pelvic cavity is
      reported. The patient, a 4-month-old girl, was referred to our department for the
      examination and treatment of her left abdominal mass. As radiological studies
      strongly suggested the possibility of a malignant tumor of muscular origin, tumor
      extirpation was performed. The tumor was buried in the left psoas muscle.
      Histological examination showed the tumor consisted of polygonal cells containing
      small vacuoles with scattered Touton giant cells, and the diagnosis of JXG was
      made. To our knowledge, this is the first case of a pelvic JXG.

PMID- 7577867
TI  - Congenital extra-hepatic portocaval shunt. Concerning a case of antenatal
      diagnosis.
AB  - The authors report a case of congenital extra-hepatic portocaval shunt in a two
      year-old girl. While pointed out antenatally by ultrasound and suspected by a
      follow-up ultrasound at the age of two years, this anomaly could be confirmed
      only by coupled ultrasound scanning and color Doppler, which allows for dynamic
      anatomic and morphologic evaluation. Comments concern mainly the embryologic
      hypothesis and the clinical tolerance of this malformation (because no
      therapeutic measures were adopted).

PMID- 7577870
TI  - Accessory diaphragm--review of 31 cases in the literature.

PMID- 7577869
TI  - Urinary fungal bezoars in children--report of two cases.
AB  - We report two cases of urinary obstruction by fungal bezoars in full-term
      neonates who presented a uropathy detected antenatally. Early percutaneous
      urinary diversion was performed to relieve renal impairment secondary to a
      primary megaureter in the first case and to bilateral pelvi-ureteral obstruction
      in the second. Acute fungal obstruction occurred first on the side of the primary
      megaureter and then on the healthy side in the first patient. Symptoms of
      infection and impaired renal function led to a diagnosis of fungal bezoar. In the
      second patient the development of the bezoar was more insidious and occurred
      after surgical correction of the obstructive pelvi-ureteral junction on the left
      side. Candiduria was the first sign in both cases. Ultrasonography is the best
      method to visualize fungal masses within the collecting system. In most cases,
      percutaneous nephrostomy allows relief of the obstruction, sampling of urine for
      culture and irrigation with amphotericin B. However, additional surgical
      intervention may be necessary. Systemic antifungal treatment using mainly 5
      flucytosine is also given.

PMID- 7577871
TI  - Location of the centre of resistance for the nasomaxillary complex studied in a
      three-dimensional finite element model.
AB  - The purpose of this study was to investigate the location of the centre of
      resistance (CRe) for the nasomaxillary complex by the use of finite element
      analysis. A three-dimensional finite element model of the craniofacial complex,
      consisting of 2918 nodes and 1776 elements, was used for displacement analyses.
      Anteriorly and inferiorly directed forces of 9.8 N were applied at five different
      levels, parallel and perpendicular to the functional occlusal plane,
      respectively. For each loading condition, horizontal and vertical displacements
      of eight anatomic points in the complex and on the maxillary dentition were
      analysed. The complex exhibited an almost translatory displacement of
      approximately 1.0 microns in the forward direction when the horizontal force was
      applied at a point on the horizontal plane, passing through the superior ridge of
      the pterygomaxillary fissure, whereas the complex experienced clockwise or
      counter clockwise rotation when the forces were applied at the remaining levels.
      Furthermore, the downward forces produced anteriorly upward, or posteriorly
      upward rotation. However, the force applied at a point on the vertical plane
      passing through the posterior wall of the pterygomaxillary fissure, produced
      almost equal displacements of approximately 6.0 microns in an inferior direction
      for all the anatomic points. It is suggested that CRe of the nasomaxillary
      complex is located on the posterosuperior ridge of the pterygomaxillary fissure,
      registered on the median sagittal plane.

PMID- 7577872
TI  - Ex vivo bond strength of adhesive precoated metallic and ceramic brackets.
AB  - Compared with conventional adhesive systems, adhesive precoated (APC) are
      reported to have advantages in clinical use. The ex vivo bond strength to human
      premolar teeth of metallic and ceramic APC brackets was compared with that of
      identical brackets bonded with Transbond (3M Unitek) light cured orthodontic
      adhesive, and patterns of failure were examined. There was no significant
      difference (P > 0.05) in mean bond strength between metallic brackets bonded with
      the two systems. Ceramic brackets bonded with Transbond had significantly higher
      (P < 0.05) mean bond strength and failure more normally occurred at the
      composite/enamel interface when compared with APC ceramic brackets and metallic
      brackets. Following debonding no enamel damage was observed with either APC or
      conventionally bonded ceramic brackets.

PMID- 7577873
TI  - Shear bond strength of orthodontic brackets treated with Sebond.
AB  - Previous studies have shown that due to poor adhesion between bonding resins and
      stainless steel orthodontic brackets, this interface remains a weak link in
      clinical orthodontic practice. A paste-like substance, Sebond, has been developed
      in order to strengthen the weak link between metal and resin. The present study
      was carried out to determine the effect on the shear bond strength, of
      pretreating the bracket base with Sebond. Two composite resins, Concise
      Orthodontic Bonding System and Nimetic-Grip were tested, using 40 orthodontic
      brackets for each resin; 20 brackets were pretreated with Sebond and the
      remaining 20 acted as controls. Of the Sebond brackets 10 were sandblasted prior
      to Sebond application. The bonded brackets were stored in water at 37 degrees C
      for 14 days after which they were tested to failure in the shear mode. Analysis
      of the results, using a general linear models analysis, showed that pretreating
      the brackets with Sebond significantly reduced shear bond strength (P < 0.001).

PMID- 7577874
TI  - A clinical investigation of the effects of omission of pumice prophylaxis on band
      and bond failure.
AB  - One hundred and twelve first molar bands and 614 directly bonded brackets on
      incisor, canine, and premolar teeth were included in a clinical trail to
      investigate the importance of omission of pumice prophylaxis at the time of
      banding and bonding, on their possible subsequent failure. Half of the sample
      were selected for the non-pumiced test groups using a random number allocation
      method, the remaining pumiced teeth acting as control groups. Two etch times were
      used for the direct bonding part of the study, 15 and 60 seconds, with non
      pumiced test and pumiced control groups included within both etch-time groups.
      Results showed no statistical difference in the failure rate of attachments in
      either test or control groups during the course of treatment. The different etch
      times had no significant effects in the direct bonding part of the study.

PMID- 7577875
TI  - Post-retention crowding and incisor irregularity: a long-term follow-up
      evaluation of stability and relapse.
AB  - The aim of the present long-term follow-up study of orthodontically-treated
      patients (mean: 15.7 years) was to analyse post-retention changes and to reveal
      factors which may play a role as predictors for long-term prognosis.
      Pretreatment, end-of-treatment, and post-retention models of 226 cases with all
      types of anomaly were used to measure intercanine and intermolar width, arch
      length, and sum of the mesiodistal dimension of the incisors, Irregularity Index,
      crowding, molar and canine relationship, overjet, and overbite. In order to
      assess the influence of sex, initial and end-of-treatment alignment, type of
      therapy, amount of tooth movement, and presence of third molars on the extent of
      post-retention changes, the total sample was divided into subgroups. Findings
      indicated that post-retention crowding and incisor irregularity increased more
      frequently in the mandible than in the maxilla. Pretreatment variables such as
      increased mesiodistal incisor dimension, severe crowding and incisor
      irregularity, arch length deficiency, arch constriction, and increased overbite
      as well as post-treatment spacing, arch expansion, increased arch length, and
      residual Class II or III molar relationships were found to be associated factors
      in the process of post-retention increase of crowding and incisor irregularity.
      'Overexpansion' was found to be a factor in mandibular incisor relapse.

PMID- 7577876
TI  - The ranking of dental aesthetics.
AB  - This study examined the effectiveness of three different aesthetic ranking
      systems. The Aesthetic Component of the Index of Orthodontic Treatment Need (10
      photographs), a numerical scale illustrated with three photographs and a
      numerical scale with only two photographs were assessed. Ten general dental
      practitioners ranked the attractiveness of dentitions using each aesthetic scale.
      A greater tendency to underscore was detected when the dentists used the two
      photograph scale. Reducing the number of photographs in the aesthetic scale did
      not significantly improve the dentists ability to rank dental aesthetics.

PMID- 7577878
TI  - A technique for the computerized identification of orthodontic instruments.
AB  - Increasingly, orthodontic instruments must leave the chairside or even the clinic
      in order to facilitate adequate sterilization. The tray system employed in an
      orthodontic clinic is outlined. Inevitably, there are problems with instruments
      being lost from these trays and finding some method for individual 'tagging',
      which is also resistant to autoclaving, would be a useful facility. To address
      this problem a robust procedure of automatic instrument identification, similar
      to bar coding, has been deployed. This system, termed matrix coding, not only
      facilitates easy instrument identification, but also allows every episode of
      clinical use and sterilization to be recorded. By such a method it could become
      possible to quickly establish when instruments are likely to require servicing,
      sharpening or replacement.

PMID- 7577877
TI  - Discontinued orthodontic treatment in the general dental services of England and
      Wales (1990-1991).
AB  - Relevant feature of a sample of discontinued treatments were investigated,
      including status at the start and at the time of discontinuation. In a comparison
      between two discontinued groups, those patients who simply failed to return
      tended to have lower pretreatment PAR scores, and were more likely to have
      received non-extraction treatments in which removable appliances were employed.
      However, when discontinued treatments were compared to completed treatments
      undertaken in 1987/8, the completed cases were only reduced by two further PAR
      points.

PMID- 7577879
TI  - Direct bonding to unerupted teeth using light-cured adhesive.
AB  - A technique is described for bonding gold traction chain directly to the enamel
      surface of unerupted teeth using a visible light-cured adhesive. This method
      obviates the need for a bracket and relies on direct, rather than transmitted
      illumination.

PMID- 7577881
TI  - Dilaceration of a permanent mandibular incisor. A case report.
AB  - A case is described where a permanent mandibular incisor was found to be
      dilacerated. Histological examination of the extracted tooth was consistent with
      trauma, although there was no supporting history. These findings are discussed
      and the orthodontic implications are considered.

PMID- 7577880
TI  - Displacement of maxillary canines: a twist in the root.
AB  - This report describes two cases in which the possible aetiology of displacement
      of a maxillary canine was the presence of a deviated root on the adjacent
      maxillary first premolar.

PMID- 7577882
TI  - Mouthguards and orthodontic treatment.

PMID- 7577883
TI  - GTCO lightmaster translucent digitizing system GTLM-1111A.

PMID- 7577884
TI  - The Dental Practice Board. Orthodontics--the current status.

PMID- 7577885
TI  - Physical activity, body composition and bone density in ballet dancers.
AB  - The main purpose of the present study was to examine factors that affect bone
      mineral density (BMD) in female ballet dancers. Training history, Ca intake, body
      composition, total body BMD (TBMD) and site-specific BMD, and bone mineral
      content were described in twenty-four female ballet dancers (mean age 22.6 (SD
      4.5) years). Training history was determined by questionnaires, Ca intake by 7 d
      dietary record, BMD and bone mineral content by dual-energy X-ray absorptiometry
      (DXA), total body water by 2H dilution, extracellular water by bromide dilution,
      body fat by underwater weighing (UWW; two-component model), DXA, and the four
      component (4C) model. Dancers had a significantly lower body mass index (BMI 18.9
      (SD 1.0) kg/m2) than controls (21.3 (SD 1.9) kg/m2), with significantly lower
      percentage body fat (17.4 (SD 3.9) v. 24.4 (SD 5.1)) but comparable fat-free
      mass. Mean TBMD (1.147 (SD 0.069) g/cm2) was significantly higher (6%) compared
      with that of a reference population. These high values could be attributed to the
      high BMD of legs and pelvis, the weight-bearing sites of the dancer's body. No
      relationship was found between age, start of ballet classes, period (years) of
      dancing, Ca intake, and BMD (total and site-specific). However, TBMD was
      positively related to BMI, and negatively related to the age of menarche. BMD of
      the legs was significantly related to BMI, and negatively related to the age of
      menarche. BMD of the legs was significantly related to daily period (h) of
      training. Depending on the method used the percentage body fat ranged from 16.4
      (by DXA) to 18.3 by the 4C model. These differences were significantly related to
      the TBMD. Percentage body fat by the different methods was not significantly
      different, except for DXA and 4C model. The present study showed that, despite
      the factors that have a negative effect on BMD, such as low body mass and late
      menarche, BMD in female ballet dancers was relatively high. These high values
      were probably caused by high levels of weight-bearing physical activity.

PMID- 7577886
TI  - Nutrient intake and biochemical status of non-instutionalized elderly subjects in
      Norwich: comparison with younger adults and adolescents from the same general
      community.
AB  - The Department of Health (1992) has recently stated that 'Nutritional reviews
      concerning elderly people are especially constrained by lack of data', and that
      much of the emphasis in the nutritional literature has been placed on the study
      of institutionalized, and often chronically ill, elderly subjects rather than the
      non-institutionalized elderly who form the majority of this population. The
      present study presents information on the dietary intake and biochemical status
      of non-institutionalized elderly subjects (68-73 and 74-90 years) and compares
      such data with those obtained for adult (20-64 years) and adolescent (13-14
      years) populations living within the same community. Nutrient intakes and
      appropriate biochemical measurements of nutrient status, performed on fasting
      blood samples, were statistically examined and have been discussed in relation to
      potential age-related influences. The nutrient intake of elderly subjects was on
      a par with adolescents of corresponding sex but generally lower than that of
      adult counterparts. There were several significant differences in biochemical
      measurements of nutrient status between age groups. In general these did not
      suggest progressive age-related trends. However, there were significant
      suggestions of age-related increases in whole-blood glutathione peroxidase (EC
      1.11.1.9) activity, serum ferritin, plasma cholesterol, LDL and triacylglycerol
      concentrations and decreases in plasma HDL and ascorbic acid concentrations. The
      significance of these differences is discussed. An age-related difference
      (suggestive of a decline) in vitamin C status together with a difference
      (suggestive of an increase) in glutathione peroxidase activity may indicate an
      imbalance in the regulation of O2-derived free-radicals with ageing. These
      observations are worthy of a further study in the light of current thinking which
      relates the induction of a number of diseases to oxidative damage.

PMID- 7577888
TI  - Measurement of protein turnover in normal man using the end-product method with
      oral [15N]glycine: comparison of single-dose and intermittent-dose regimens.
AB  - The 'single-dose end-product' approach for the measurement of protein turnover is
      the only method suited for application to free-living individuals and for field
      studies. However, the method has never been widely accepted because the results
      obtained appear to vary from one situation to another. There is the need for a
      formal comparison of the different approaches that have been used and the
      assumptions on which they are based in order to be able to understand the extent
      to which the variation in the results obtained is real or might be attributed to
      methodological differences. The present study used the 'prime/intermittent-dose
      end-product' approach over 18 h as a reference with which to compare the 'single
      dose end-product' approach, with urine being collected for periods of 9 to 48 h.
      N flux was derived in a total of thirteen normal men using oral [15N]glycine and
      measurement of 15N enrichment in urinary NH3 or urea, with isotope being given
      either as prime/intermittent doses or a single dose in separate studies. The
      pattern of results was similar to those reported in the literature. In all
      studies the rates of N flux derived from urea were higher than those derived from
      NH3, under equivalent conditions, by about 25-30%. The single-dose approach, with
      urine collection over 9 h, gave results which were consistently higher than the
      prime/intermittent-dose approach. The extent of the difference was influenced by
      the duration of time over which the cumulative excretion of isotope in urine was
      determined, and with NH3 as the end-product the most consistent estimates of N
      flux could be obtained with a urine collection of at least 12 h and no greater
      than 24 h. With urea as the end-product, correction for the label retained in the
      body pool at 9 h gave similar results for N flux to those derived from the total
      excretion of label in urea over 24 h. The derivation of values for protein
      synthesis and protein degradation from measures of flux requires care to ensure
      that the time periods over which N intake and excretion are measured accord with
      those for which the measurement of flux apply. It is concluded that measurements
      of protein turnover similar to those obtained with the prime/intermittent-dose
      approach can be obtained with the single-dose approach in the fed state during
      the daytime, either from the excretion of label in urinary NH3 over a period of
      12 h or with the excretion of label in urinary urea over a period of 24 h. The
      suitability of the method for use in the fasted state or at night time remains to
      be determined.

PMID- 7577887
TI  - The effects of fasting on the thermogenic, metabolic and cardiovascular responses
      to infused adrenaline.
AB  - The effects of fasting on the thermogenic, lipolytic and cardiovascular responses
      to adrenaline were examined in nine normal, young, non-obese subjects. Each
      subject attended for study after 12, 36 and 72 h fasting. After basal
      measurements adrenaline was infused at 25 ng/min per kg ideal body weight for 90
      min. Fasting increased the thermogenic effect of the adrenaline (mean 14.6 (SE
      1.7), 16.6 (SE 1.8), 22.6 (SE 1.6) J/min per kg fat-free mass after 12, 36 and 72
      h fasting respectively; P < 0.001, ANOVA). Basal plasma palmitate turnover
      increased with duration of fasting (1.48 (SE 0.22), 1.95 (SE 0.34) and 2.26 (SE
      0.33) mumol/min per kg body weight; P < 0.001, ANOVA), but the response to
      adrenaline was unaffected by fasting. The percentage values for basal plasma
      palmitate turnover oxidized were 44 (SE 2; 12 h), 46 (SE 5; 36 h) and 42 (SE 4)%
      (72 h). In response to adrenaline this percentage fell, suggesting that
      adrenaline infusion may favour intra-tissue lipid oxidation.

PMID- 7577889
TI  - Replacement of dietary saturated fat with monounsaturated fat: effect on
      atherogenesis in cholesterol-fed rabbits clamped at the same plasma cholesterol
      level.
AB  - The aim was to compare the effect on atherogenesis of dietary monounsaturated and
      saturated fatty acids in cholesterol-clamped rabbits. To obtain an average plasma
      cholesterol concentration of 20 mmol/l in each rabbit during the 13-week
      cholesterol-feeding period, dietary cholesterol was adjusted weekly. The amount
      of fat fed daily was 10 g per rabbit in Expts A (n 23), C (n 36), and D (n 58)
      and 5 g per rabbit in Expt B (n 24). The source of monounsaturated fatty acids
      was olive oil in all four experiments. The source of saturated fatty acids was
      butter in Expt A, lard in Expt B, coconut oil in Expt C, and butter or lard in
      Expt D. Generally, olive oil-fed groups received more cholesterol and tended to
      have more cholesterol in VLDL and less in LDL compared with groups receiving
      saturated fat. Analysis of variance of the combined results of all four
      experiments showed that, in comparison with saturated fat, olive oil lowered
      aortic cholesterol by 13 (-9-30, 95% confidence interval) % in the aortic arch,
      and by 10 (-10-26) % in the thoracic aorta, which was not significant. In the
      comparison with olive oil, no differences in effects on aortic cholesterol
      content were detected between butter, lard and coconut oil. These findings do not
      support the view that replacement of dietary saturated fat with olive oil has a
      major impact on the development of atherosclerosis in addition to that accounted
      for by changes in plasma cholesterol levels.

PMID- 7577891
TI  - Measurement of starch digestion of naturally 13C-enriched weaning foods, before
      and after partial digestion with amylase-rich flour, using a 13C breath test.
AB  - Malnutrition in infancy is a global problem which leads to retardation of
      childhood growth and development. There is a pressing need to improve weaning
      strategies for infants of the developing world. Traditional Gambian weaning foods
      are watery and of low energy density, but addition of energy in the form of fat
      and carbohydrate leads to thick, viscous gruels which are difficult to ingest.
      Partial digestion with amylase (EC 3.2.1.1)-rich flour reduces their viscosity
      while retaining their energy density. The aim of the present study was to measure
      the digestibility of a maize-based weaning food, before and after amylase
      digestion, in malnourished children using a 13C breath test. Ten children (aged 7
      16 months; mean weight-for-age Z score -0.8) received isovolumetric and
      isoenergetic quantities of a maize-based weaning food naturally abundant with
      13C. Breath samples were collected at intervals of 30 min for 5 h thereafter and
      13CO2 enrichment was measured by isotope-ratio mass spectrometry. Percentage dose
      of 13C recovered increased from a mean 13.7 (SD 3.7)% before, to 18.3 (SD 5.6)%
      after ingestion of amylase-treated weaning foods (P < 0.1). There was a
      significant inverse relation between age and weight, and percentage dose of 13C
      recovered in children receiving amylase-treated feeds. There were no differences
      in concentrations of amylase in saliva of infants or breast milk of their
      mothers. Partial digestion of supplementary foods may improve the nutrition of
      undernourished weaning children, not only by reducing their viscosity, thereby
      increasing ingestion, but also by improving their digestion and thereby their
      absorption.

PMID- 7577890
TI  - Effect of dried Bacillus subtilis culture on growth, body composition and hepatic
      lipogenic enzyme activity in female broiler chicks.
AB  - To investigate the effect of dried Bacillus subtilis culture on growth, body
      composition and hepatic lipogenic enzyme activity, female broiler chicks were fed
      on either no additive (control) or dried B. subtilis-culture-supplemented
      commercial diets (215 g crude protein/kg, 12.85 MJ metabolizable energy/kg) at 10
      or 20 g/kg diet for 28 d from 14 to 42 d of age. Body weight, and moisture, fat,
      protein and ash contents of the body were not influenced by the B. subtilis
      culture. Feed efficiency, N utilization, the ratio of abdominal fat or liver to
      body weight, acetyl-coenzyme A carboxylase (EC 6.4.1.2) activity, liver and serum
      cholesterol contents were significantly lower in treatment groups, while fatty
      acid synthetase activity and serum cholesterol concentration were not
      significantly different, compared with the control group. Liver triacylglycerol
      concentration was decreased in chicks given 20 g culture/kg diet, while serum and
      carcass triacylglycerol concentrations were significantly lower in treatment
      groups than in the control group. Serum phospholipid concentration was increased
      but carcass phospholipid concentration was decreased in chicks given 20 g B.
      subtilis/kg diet, while liver phospholipid concentration was not significantly
      influenced. The advantages of inclusion of B. subtilis to the broiler diet
      included improved feed efficiency, less abdominal fat, reduced triacylglycerol
      concentrations in the liver, serum and carcass and reduced cholesterol
      concentrations in the liver and carcass.

PMID- 7577892
TI  - The effect of high-molecular-weight guar gum on net apparent glucose absorption
      and net apparent insulin and gastric inhibitory polypeptide production in the
      growing pig: relationship to rheological changes in jejunal digesta.
AB  - The present study was designed to determine the quantitative effects of starchy
      meals containing guar gum on rates of net apparent glucose absorption and net
      apparent insulin and gastric inhibitory polypeptide (GIP) production in growing
      pigs. The effects of these meals on the viscosity of jejunal digesta were also
      examined and correlated to changes in glucose absorption. Four growing pigs were
      each given either a low-fat semi-purified diet (control) or the same diet
      supplemented with a high-molecular-weight guar gum at concentrations in the diet
      of 20 or 40 g/kg. Blood samples were removed simultaneously via indwelling
      catheters from the mesenteric artery and the hepatic portal vein. Samples of
      jejunal digesta were removed via a T-piece cannula and used immediately for
      viscosity measurements at 39 degrees. The 'zero-shear' viscosity of each sample
      was then calculated. Blood-flow measurements were made using an ultrasonic flow
      probe fitted to the hepatic portal vein. All measurements were made at intervals
      of 10 or 30 min during a 4 h postprandial period. Meals containing guar gum
      significantly increased (P < 0.05) the viscosity of jejunal digesta, an effect
      that was strongly dependent on the concentration of guar gum in the original
      diet. No significant differences in blood-flow rates were found between the
      control and guar-containing diets. Both concentrations of guar gum significantly
      reduced (P < 0.05) glucose absorption and insulin and GIP secretion rates over
      the 4 h postprandial period. An inverse relationship between the rate of glucose
      absorption and the 'zero-shear' viscosity of jejunal digesta was found. This
      study also provides direct evidence for the important role played by the
      enteroinsular axis in modifying the glycaemic response to a meal containing guar
      gum.

PMID- 7577893
TI  - Long-term oral refeeding of patients with cirrhosis of the liver.
AB  - A previous study has shown that malnourished, clinically stable patients with
      liver cirrhosis are in protein and energy balance at their spontaneous dietary
      intake and that an improvement in nutritional status cannot be anticipated at
      this intake (Nielsen et al. 1993). In the present study we examined to what
      extent oral intake could be increased by nutritional support, and to what extent
      dietary protein would be retained with increased intake. The techniques used for
      balance studies were also validated since this information is not available for
      patients with liver cirrhosis. Fifteen malnourished patients with alcoholic liver
      cirrhosis were given increasing amounts of a balanced ordinary diet for 38 (SE 3)
      d. Intakes of protein and energy were recorded by weighing servings and leftovers
      on food trays. Protein intake was calculated from food tables. Total N disposal
      was calculated after measurement of urinary N excretion, and protein balance was
      calculated from the N balance. A validation study of protein balance in a
      subgroup of patients (analysis of N in food by the duplicate portion technique,
      correction for incomplete recovery of urine by measurement of urinary para
      aminobenzoic acid (PABA) after administration of PABA tablets, and measurement of
      faecal N) did not change protein balance values. Protein intake increased from
      1.0 (SE 0.1) g/kg per d to 1.8 (SE 0.1) g/kg per d. With increasing protein
      intake, 84 (SE 8)% of the increase in intake was retained. The rate of protein
      retention was not saturated at the intakes obtained in this study. Protein
      intolerance was only encountered in one patient. Available evidence indicates
      that the requirement for achieving N balance is increased in these patients but
      protein retention is highly efficient with increased intake. Protein retention is
      dependent on energy balance. Energy intake was calculated from food tables and
      total energy expenditure was calculated by the factorial method. A validation
      study was performed in a subgroup of patients. The energy contents of food
      sampled by the duplicate portion technique, and of urine and faeces were measured
      by bomb calorimetry. Resting energy expenditure (REE) was measured by indirect
      calorimetry before and at the end of the study, and O2 uptake during bicycle
      exercise was measured before and at the end of the study. The measured intake of
      metabolizable energy was on average 13% lower than the value given in food
      tables. Calculated energy expenditure was not changed by the validation
      study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577894
TI  - Short-term satiating effect of the fat replacer sucrose polyester (SPE) in man.
AB  - The effects of different amounts of the non-absorbable fat replacer sucrose
      polyester (SPE), water, and fat added to six warm preload lunches on feelings of
      appetite and food intake were investigated in two studies that were replicates of
      each other. In the first study thirty-nine subjects consumed rice preloads; in
      the second study thirty-five subjects consumed macaroni preloads. The six
      preloads were fixed on three energy levels: 1.8, 2.7, or 3.7 MJ. At 2 h after
      preload consumption a test-meal buffet of thirty-one products was presented. Food
      intake was recorded on the study day, and the day after the study day. For women
      no energy compensation occurred in either study. Men showed a tendency to
      compensate for the energy differences between the preloads. However, when the fat
      of the preloads was replaced by SPE, energy compensation was less than 50% and
      non-significant. Statistically significant energy compensation (66%) was found
      when fat was replaced by water. No macronutrient-specific compensation occurred
      in men or women in either study. Lower total fat and energy intakes were found
      with the preloads where fat was replaced by SPE compared with the preloads
      containing fat. The appetite ratings were in line with the energy intake values,
      with no differences in women, and higher appetite ratings after the lower energy
      preloads in men. This short-term study indicates that SPE may be a useful aid to
      reduce fat and energy intakes.

PMID- 7577896
TI  - [Tonography: myth or reality].

PMID- 7577895
TI  - Biological effects of isoflavones in young women: importance of the chemical
      composition of soyabean products.
AB  - To examine the hormonal effects of isoflavones, of which soyabean is a rich
      source, fifteen healthy nonvegetarian premenopausal women were studied over 9
      months. They lived in a metabolic suite for between 4 and 6 months where their
      diet and activity levels were kept constant and their hormonal status was
      measured over two or three menstrual cycles. During one (control) menstrual cycle
      a normal but constant diet containing no soyabean products was fed. Then, over a
      second complete cycle six subjects consumed a similar diet into which 60 g
      textured vegetable protein (TVP)/d, containing 45 mg conjugated isoflavones, had
      been incorporated. Three participants had 50 g miso (a fermented soyabean paste),
      containing 25 mg unconjugated isoflavones, added daily to their diet over a
      menstrual cycle, and six others consumed 28 g TVP/d, containing 23 mg conjugated
      isoflavones. Five participants completed a third diet period where they were
      randomly assigned to consume either the control diet over a cycle, or a similar
      diet incorporating 60 g of a soyabean product which had had the isoflavones
      chemically extracted (Arcon F). Follicular phase length was significantly (P <
      0.01) increased and peak progesterone concentrations were delayed with 60 g TVP
      but no effects were observed with Arcon F. The increase in menstrual cycle length
      did not reach statistical significance in the three three subject who ate 50 g
      miso/d, but peak progesterone levels were significantly (P < 0.05) delayed. Mid
      cycle peaks of luteinizing hormone (LH) and follicle stimulating hormone (FSH)
      were suppressed with 45 mg conjugated isoflavones as 60 g TVP (P < 0.05 and P <
      0.01 respectively). No other changes in sex-steroid hormone levels were observed
      on any of the other diets. A significant reduction in total cholesterol was found
      with 45 mg conjugated isoflavones (P < 0.05), but not with 23 mg conjugated
      isoflavone-free Arcon F. There was no effect of menstrual cycle phase on transit
      time.

PMID- 7577897
TI  - [The theoretical bases of functional optometry].
AB  - The visual function is based on: focalization, binocularization, identification,
      which are all related processes and integrated into the whole of human body. The
      behavioural through three main phases: structural, functional and operational.
      Each phase involves in turn three aspects: static, dynamic and control. This
      analytical method allows a better understanding of this complex phenomenon which
      is the visual function.

PMID- 7577898
TI  - [The physiopathology of primary cataract].
AB  - The alteration of the lens with the age are mainly due to the diminishing of the
      energetic metabolism, whose consequence is the diminishing of the synthesis of
      poliphosphate nucleotides and RNA, decreasing also the protein synthesis. From a
      biomolecular point of view alterations of the DNA appear, because of the increase
      in the activity of ADP-ribosyl transferasis with the age. The progress of the
      cellular biology and the knowledge of the physiopathological mechanisms implied
      in the opacification of the lens, opens new prospects in the prevention of this
      form of cataract.

PMID- 7577899
TI  - [Colobomatous fossette of the optic papilla and juxtapapillary choroidal
      malignant melanoma].
AB  - The paper presents a clinical case of colobomatous fossette of the optic nerve
      papilla complicated with macular decolation, in association with the malignant
      melanoma of the choroid. Some aspects of the pathogeny of the retinal
      decoloration are discussed in this context. Some possible corrections between the
      two border retinal decolorations--the serous interpapillary macular decoloration
      and the retinal decoloration secondary to the melanoma of the choroid--are also
      proposed.

PMID- 7577900
TI  - [The classification of secondary glaucomas].
AB  - After the presentation of the most important types of secondary glaucomas, the
      author classified these glaucomas used the same aspect known at the primary
      glaucomas classification the aspect of the iridocorneal angle. In this
      classification the open angle secondary glaucoma has three clinical forms: with
      pretrabecular, trabecular and post-trabecular obstacle. The closed angle
      secondary glaucoma has also three forms: anterior, posterior and congenital.

PMID- 7577901
TI  - [Cerebro-oculofacial dysplasia associated with vertebral changes].
AB  - A clinical case of craniofacial dysplasia, with multiple and complex congenital
      anomalies, is presented. The clinical modifications noticed are systematized in
      four groups: cerebral, ocular, facial and vertebral. The case is a form of
      cerebrofacial display, associated with anophthalmos, orbitopalpebral chist and
      vertebral modifications. There are discussed problems of differential diagnosis,
      pathogeny and therapeutical attitude.

PMID- 7577903
TI  - [Late congenital glaucoma and pigmentary retinopathy].
AB  - Two clinical observations of pigmentary retinopathy associated with late
      congenital glaucoma are presented. This associations is rarely emphasized in the
      literature, the most frequent association being of the pigmentary retinopathy and
      open angle glaucoma. In the former observation a genetical filiation could not
      been established. In the latter the heredity was autosomal recessive, with two
      existent distinct pathological genes. The genetic defect in pigmentary
      retinopathy with dominant autosomal transmission is supposed to be localized on
      the codon 216 Ser-->Pro or at the level of the codon 296 by the substitution Lys-
      >Glu and Lys-->Met for the some determination, but done in vitro. In the
      recessive form the abnormal alleles are localized in the interval D11 5861 and
      D11 5899.

PMID- 7577902
TI  - [The efficacy of a microtrabecular prosthesis in the surgery of refractory
      glaucomas].
AB  - A new model of intermediate artificial drainage system (called
      microtrabeculoprosthesis--MTP) in the surgery of refractory glaucoma is
      suggested. The prospective study includes 37 operated cases followed up for an
      average interval of 18.2 months (ranges 11 and 72 months). Surgery is not
      difficult, and MTP is very well tolerated. A relief of elevated intraocular
      pressure (IOP < or = 20 mm Hg) was obtained in 73% of the cases (with or without
      additional antiglaucoma drugs); the irritative phenomena have disappeared in
      preterminal and absolute glaucoma; the overall therapeutic success rate was
      86.5%. The results obtained with MTP are definitely superior to those by
      conventional surgery but inferior to modern posterior artificial drainage systems
      (with ameliorative techniques); the rate of postoperative complications is small,
      and their severity is minimal. In the absence of modern posterior artificial
      drainage systems. MTP is an efficient solution for the treatment of refractory
      glaucoma.

PMID- 7577904
TI  - [Persistence of the primordial vitreous body and buphthalmos].
AB  - Persistence of the hyperplasic primordial vitreous body is determined by a
      deletion of embryonal development of the vitreous body and of the hyaloid
      vascular system. Infant aged 3.5 years presents persistence of primordial
      vitreous body with crystalline dislocation in the camera aquosa and secondary
      buphthalmos of the left eye and microphthalmos with dislocation of the
      crystalline in the vitreous body of the right eye. At the back of the right eye
      we noticed a whitish mass, richly vascularized with vestiges from the hyaloid
      artery, but the posterior half of the vitreous cavity is filled with microscopic
      blood; the fibrovascular membrane is made of conjunctive tissue set in parallel
      layers and vessels with macrolipophagic degeneration. Microscopic investigation
      of retina reveals glial hyperplasia zones in the neighbourhood of the vitreous
      body. In the present paper the authors show the persistence of the primordial
      vitreous body in the left eye and bilateral dislocation of the crystalline,
      revealing multiple ocular malformations.

PMID- 7577905
TI  - [Corneal edema, a complication of cataract surgery].
AB  - The paper presents data from the literature regarding the physiology and
      physiopathology of the corneal oedema and also some clinical and therapeutical
      aspects about corneal oedema secondary to the cataract operation. The physiology
      and physiopathology of the corneal oedema is discussed with respect to the
      enzymatic support, development processes of the corneal oedema, and also the
      operation stress produced by the cataract surgery. The corneal oedema following
      the cataract operation is presented with its clinical aspects (early and late) of
      the paraclinical determination (pachymetric, microspecular) and also of the
      therapeutical indications (transfixiante keratoplasty).

PMID- 7577906
TI  - [Juvenile hemorrhagic macular choroidopathy].
AB  - A clinical case of juvenile macular hemorrhagic choroidopathy is presented. The
      affection is distinguished by the appearance to a young adult of a placard of
      neuroepithelium serous decoloration, and also by macular hemorrhages and the
      absence of other local or general inflammatory implications. This clinical case
      is interesting because of the very young age limit at which the illness appeared.
      Other elements of diagnosis, pathogeny and treatment are also discussed.

PMID- 7577908
TI  - [The cicatrization of corneal wounds].
AB  - The tissular mending of the corneal surface is the result of a complex series of
      various physiopathological responses. This structural regeneration involves a
      primary reconstruction and a secondary one. The primary reconstruction of the
      barrier function provides the restoring of the normal equilibrium of osmotic,
      thermal and metabolic exchanges. The primary cicatricial response's goal is the
      fast coating of the corneal plague and mainly involves an inflammatory response.
      The major stages of this initial sequence are: the migration of the polynuclear
      neutrophils into the plaque, the establishment of a fibrinous cork, the
      collapsing and then the migration of the epithelial cork, and the contraction of
      the keratocyte mesh.

PMID- 7577907
TI  - [The atypical ophthalmologic onset of acute Devic neuromyelitis].
AB  - A case of Devic's acute neuromyelitis with an atypical ophthalmic debut is
      presented. Usually, the Devic's neuromyelitis starts by concomitant alteration of
      both eyes. In the described case, the condition debut has been monocular (OD), as
      a juxtabulbar optic neuritis, after a respiratory viral infection. The
      neurological syndrome (paraplegia) and the acute renal failure appeared one week
      after the viral debut, the patient having been transferred to the neurology
      department, where, under cortisone treatment the ophthalmological phenomena
      disappeared completely, remaining only the neurological condition (tetraplegia).

PMID- 7577909
TI  - [The indications for vitrectomy in retinal detachment].
AB  - The modern vitreous surgery has rapidly developed during the last 2 decades,
      becoming an effective part of the treatment, in most retinal detachments that
      cannot be treated by the classical means. This study points out the main types of
      retinal detachment in which vitrectomy is indicated, as its place in the complex
      therapeutical sequence. It is based on the studies of ophthalmologists with
      experience in vitrectomy is indicated, as its place in the complex therapeutical
      sequence. It is based on the studies of ophthalmologists with experience in
      vitreous surgery. If there continue to be controversies on vitrectomy's
      indications and moment, the fact that vitrectomy has radically changed the
      prognosis and therapeutical attitude in severe retinal detachments, is
      unanimously admitted. Most retinal detachments (the rhegmatogenous, uncomplicated
      one) continue to be treated by the classical means: scleral buckling+Rupture's
      blockage.

PMID- 7577910
TI  - Measuring the strength of side-chain hydrogen bonds in peptide helices: the
      Gln.Asp (i, i + 4) interaction.
AB  - Whether hydrogen bonds between side chains are energetically significant in
      proteins and peptides has been controversial. A method is given here for
      measuring these interactions in peptide helices by comparing the helix contents
      of peptides with 1, 2, or 3 interactions. Results are given for the glutamine-
      aspartate (i, i + 4) hydrogen-bond interaction. The Gibbs energy of the
      interaction is -1.0 kcal/mol when aspartate is charged and -0.4(4) kcal/mol when
      it is protonated. Magnetic resonance experiments show that the aspartate
      carboxylate group interacts specifically with the trans amide proton (HE) of
      glutamine. The interaction is observed only when the glutamine residue is N
      terminal to the aspartate and when the spacing is (i, i + 4). The same
      stereochemistry is found in protein structures, where the (i, i + 4) glutamine
      aspartate interaction occurs much more frequently than other possible
      arrangements.

PMID- 7577911
TI  - Fructose-1,6-bisphosphatase: arginine-22 is involved in stabilization of the T
      allosteric state.
AB  - A comparison of the X-ray crystallographic structures of the R and T allosteric
      states [Ke, H. M., Liang, J.-Y., Zhang, Y., & Lipscomb, W. N. (1991) Biochemistry
      30, 4412-4420] of the pig kidney fructose-1,6-bisphosphatase (EC 3.1.3.11)
      reveals major changes in the quaternary structure of the enzyme upon the binding
      of the allosteric inhibitor AMP. This change in quaternary structure involves the
      breaking of one set of interactions that stabilize the R state and the formation
      of another set of interactions that stabilize the T state of the enzyme. In
      particular, the interactions of Arg-22 with nearby amino acid residues are quite
      different in the R and T states of the enzyme. Although the crystallographic data
      suggest that intersubunit interactions such as those involving Arg-22 are
      important for stabilization of the R and/or T states, the X-ray structures do not
      provide direct evidence concerning the functional role of specific amino acid
      residues. Therefore, site-specific mutagenesis has been used to probe the
      function of Arg-22 in pig kidney fructose-1,6-bisphosphatase. The replacement of
      Arg-22 by Ala results in a mutant enzyme with enhanced catalytic efficiency
      compared to the wild-type, as indicated by a kinetic analysis showing a slightly
      lower Km and increased Vmax compared to the wild-type enzyme. In addition, the
      substitution enhances both substrate inhibition and the affinity of the inhibitor
      fructose 2,6-bisphosphate. Moreover, the replacement of Arg-22 by Ala results in
      a more than 10-fold loss of the ability of AMP to inhibit the enzyme.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577912
TI  - Catalytic strategy of citrate synthase: subunit interactions revealed as a
      consequence of a single amino acid change in the oxaloacetate binding site.
AB  - The active site of pig heart citrate synthase contains a histidine residue (H320)
      which interacts with the carbonyl oxygen of oxaloacetate and is implicated in
      substrate activation through carbonyl bond polarization, a major catalytic
      strategy of the enzyme. We report here the effects on the catalytic mechanism of
      changing this important residue to glycine. H320G shows modest impairment in
      substrate Michaelis constants [(7-16)-fold] and a large decrease in catalysis
      (600-fold). For the native enzyme, the chemical intermediate, citryl-CoA, is both
      hydrolyzed and converted back to reactants, oxaloacetate and acetyl-CoA. In the
      mutant, citryl-CoA is only hydrolyzed, indicating a major defect in the
      condensation reaction. As monitored by the carbonyl carbon's chemical shift, the
      extent of oxaloacetate carbonyl polarization is decreased in all binary and
      ternary complexes. As indicated by the lack of rapid H320G--oxaloacetate
      catalysis of the exchange of the methyl protons of acetyl-CoA or the pro-S
      methylene proton of propionyl-CoA, the activation of acetyl-CoA is also faulty.
      Reflecting this defect in acetyl-CoA activation, the carboxyl chemical shift of
      H320G-bound carboxymethyl-CoA (a transition-state analog of the neutral enol
      intermediate) fails to decrease on formation of the H3020G-oxaloacetate
      carboxymethyl-CoA ternary complex. Progress curves and steady-state data with
      H320G using citryl-CoA as substrate show unusual properties: substrate inhibition
      and accelerating progress curves. Either one of two models with subunit
      cooperativity [Monod, J., Wyman, J., & Changeux, J.-P. (1965) J. Mol. Biol. 12,
      88; Koshland, D. E., Jr., Nemethy, G., & Filmer, D. (1966) Biochemistry 5, 365]
      quantitatively accounts for both the initial velocity data and the individual
      progress curves. The concentrations of all enzyme forms and complexes are assumed
      to rapidly reach their equilibrium values compared to the rate of substrate
      turnover. The native enzyme also behaves according to models for subunit
      cooperativity with citryl-CoA as substrate. However, the rates of
      formation/dissociation and reaction of complexes are kinetically significant.
      Comparisons of the values of kinetic constants between the native and mutants
      enzymes lead us to conclude that the mutant less readily undergoes a conformation
      change required for efficient activation of substrates.

PMID- 7577914
TI  - Structural investigation of the antibiotic and ATP-binding sites in kanamycin
      nucleotidyltransferase.
AB  - Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme responsible
      for some types of bacterial resistance to aminoglycosides. The enzyme deactivates
      various antibiotics by transferring a nucleoside monophosphate group from ATP to
      the 4'-hydroxyl group of the drug. Detailed knowledge of the interactions between
      the protein and the substrates may lead to the design of aminoglycosides less
      susceptible to bacterial deactivation. Here we describe the structure of KNTase
      complexed with both the nonhydrolyzable nucleotide analog AMPCPP and kanamycin.
      Crystals employed in the investigation were grown from poly(ethylene glycol)
      solutions and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions
      of a = 57.3 A, b = 102.2 A, c = 101.8 A, and one dimer in the asymmetric unit.
      Least-squares refinement of the model at 2.5 A resolution reduced the
      crystallographic R factor to 16.8%. The binding pockets for both the nucleotide
      and the antibiotic are extensively exposed to the solvent and are composed of
      amino acid residues contributed by both subunits in the dimer. There are few
      specific interactions between the protein and the adenine ring of the nucleotide;
      rather the AMPCPP molecule is locked into position by extensive hydrogen bonding
      between the alpha-, beta-, and gamma-phosphates and protein side chains. This, in
      part, may explain the observation that the enzyme can utilize other nucleotides
      such as GTP and UTP. The 4'-hydroxyl group of the antibiotic is approximately 5 A
      from the alpha-phosphorus of the nucleotide and is in the proper orientation for
      a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577913
TI  - Solution structure of the DNA-binding protein Sac7d from the hyperthermophile
      Sulfolobus acidocaldarius.
AB  - The Sac7 proteins from the hyperthermophile Sulfolobus acidocaldarius are a
      heterogeneous mixture of small, thermostable, nonspecific DNA-binding proteins.
      One of these proteins, Sac7d, has been overexpressed in Escherichia coli to
      provide a homogeneous preparation for structure, stability, and function studies.
      We present here essentially complete sequence-specific 1H NMR assignments for
      Sac7d, a delineation of secondary structural elements, and the high-resolution
      solution structure obtained from a full relaxation matrix refinement. The final
      structure provides an excellent fit to the NMR data with an NOE R-factor of 0.27
      for backbone NOEs. The structure has a compact globular fold with 82% of the
      sequence involved in regular secondary structure: an antiparallel two-stranded
      beta-ribbon with a tight turn, followed by a short 3(10) helix, an antiparallel
      three-stranded beta-sheet, another short 3(10) helix, and finally four turns of
      alpha-helix. The amphipathic alpha-helix packs across the hydrophobic face of the
      three-stranded beta-sheet in an open-faced sandwich arrangement with at least one
      turn of the helix exposed beyond the sheet. The hydrophobic face of the beta
      ribbon packs against a corner of the twisted beta-sheet. The single tryptophan
      responsible for the 88% fluorescence quenching upon DNA binding is exposed on the
      surface of the three-stranded beta-sheet. Lysines 5 and 7, whose monomethylation
      may be associated with enhanced thermostability, are highly solvent exposed along
      the inner edge of the two-stranded ribbon. The structure of Sac7d differs in many
      respects from that reported for the homologous native Sso7d [Baumann et al.
      (1994) Nature Struct. Biol. 1, 808] with a backbone RMSD greater than 3.0 A,
      largely due to the packing and length of the C-terminal alpha-helix which may be
      important in Sac7d DNA binding.

PMID- 7577915
TI  - Designing subtilisin BPN' to cleave substrates containing dibasic residues.
AB  - The bacterial serine protease, subtilisin BPN', has been mutated so that it will
      efficiently and selectively cleave substrates containing two consecutive basic
      (dibasic) residues. Mutants were designed on the basis of both the structure of
      subtilisin BPN' and considerations of sequence differences between it and
      eukaryotic homologs, Kex2, PC2, and furin, which are known to cleave dibasic
      substrates. These eukaryotic proteases have high sequence homology to one another
      but differ substantially from subtilisin BPN' in loops that interact with the
      substrate. When these loops were grafted into subtilisin BPN', the mutated enzyme
      could not be expressed, presumably due to destabilization of the folded enzyme.
      We noted that several neutral residues in subtilisin BPN' (Gly 166, Ser 33, and
      Asn 62) that are positioned to interact with a dibasic substrate are acidic
      residues at analogous positions in Kex2. Mutating these residues individually to
      either Glu or Asp in subtilisin BPN' resulted in systematic shifts in substrate
      specificity (kcat/Km) toward basic residues and away from the natural preference
      for hydrophobic substrates. A combination mutant, where Asn 62 was changed to Asp
      and Gly 166 was changed to Asp (N62D/G166D), had a larger than additive shift in
      specificity toward dibasic substrates. This unexpectedly large change was
      confirmed by detailed analysis with a variety of synthetic substrates. Additional
      substrate determinants were revealed by sorting a library of phage particles
      (substrate phage) containing five contiguous randomized residues. This method
      identified a particularly good substrate (Asn-Leu-Met-Arg-Lys) that was
      selectively cleaved in the context of a fusion protein by the N62D/G166D
      subtilisin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577916
TI  - Stoichiometry and thermodynamics of the interaction between the Fc fragment of
      human IgG1 and its low-affinity receptor Fc gamma RIII.
AB  - IgG-Fc receptors, cell surface glycoproteins binding the Fc region of antibodies,
      play a crucial role in the immune system. To better understand the nature of the
      recognition process, we have examined the interaction between huIgG1-Fc and a
      soluble fragment of huFc gamma RIII (sCD16). Analytical ultracentrifugation
      experiments clearly demonstrate that IgG1-Fc and sCD16 interact weakly to form a
      1:1 complex with an association constant of 1.7 x 10(5) M-1 in PBS at 22.0
      degrees C. The thermodynamic parameters, obtained from the temperature dependence
      of the equilibrium binding constants, exhibit an enthalpy-entropy compensation
      with a favorable enthalpy at physiological temperatures. The value of -360 cal
      mol-1 K-1 for delta Cp zero possibly identifies the process as one in which local
      folding/rearrangement is coupled to complex formation. The 1:1 stoichiometry and
      thermodynamic parameters provide a basis for understanding the nature of the Fc
      gamma R-IgG interactions.

PMID- 7577917
TI  - Divalent cation selectivity in a cyclic nucleotide-gated ion channel.
AB  - Divalent metal cation selectivity was studied in guanosine 3',5'-cyclic
      monophosphate-gated ion channels. Channels from bovine retina were expressed in
      Xenopus laevis oocytes, and currents were measured using tight-seal patch
      recording methods. The ability of divalent cations to block Na+ currents was used
      to determine the occupancy of divalent cations in the ion conduction pore. At
      positive membrane voltages, where extracellular divalent cations are near
      equilibrium with their binding site, the occupancy reflects the affinity of the
      blocking ion. The selectivity sequence based on relative affinity was Ca2+ > Mg2+
      = Sr2+ = Ba2+. In addition to its higher affinity, Ca2+ was more permeant and
      blocked with a weaker voltage dependence. Ca2+ was the only ion that blocked with
      a high Hill coefficient (n = 2.7), suggesting the presence of multiple binding
      sites. When Glu 363, located in the pore-forming region, was mutated to Asp, the
      affinity of all four ions increased and the selectivity sequence became Ca2+ >
      Sr2+ > Ba2+ > Mg2+. These results show that the channel is highly selective for
      Ca2+ and that Glu 363 mediates divalent cation selectivity of the channel.

PMID- 7577920
TI  - Multiple binding with identical linkage: a mechanism that explains the effect of
      lipoprotein(a) on fibrinolysis.
AB  - We have previously shown that both recombinant apo(a) and native Lp(a) inhibit
      the binding of Glu-plasminogen to fibrin surfaces [Fleury & Angles-Cano (1991)
      Biochemistry 30, 7630-7638; Rouy et al. (1992) Biochemistry 31, 6332-6339]. The
      aim of the present study was to characterize the mechanism of this inhibition and
      to define the parameters governing binding when two different Lp(a) species
      compete with plasminogen for fibrin, a situation that may be found in vivo in
      subjects heterozygous for the apo(a) trait. The Kd for the binding of plasminogen
      to fibrin was 660 nM whereas the affinity of Lp(a) was inversely related to
      apo(a) size (Kd range: 50 to > 500 nM). To determine the effect of plasminogen on
      Lp(a) binding and reciprocally, competition experiments were performed. The Kd of
      either Lp(a) or plasminogen for fibrin remained unchanged in the presence of the
      other competitor whereas Bmax, the maximal amount bound, was importantly
      decreased. In a similar fashion, competition for fibrin binding among Lp(a)
      isoforms was shown with the use of Lp(a) density fractions containing varying
      proportions of isoforms B (approximately 460 kDa) and S3 (approximately 640 kDa);
      variations in Kd values (from 141 nM to 460 nM) as a function of the relative
      content in isoform S3 were observed. Altogether, these results are indicative of
      multiple binding by ligands that bind with different affinities to equivalent but
      independent sites. Thus, in plasma from heterozygous subjects, the influence of
      each Lp(a) isoform on fibrinolysis will depend on their affinity for fibrin and
      on their concentration relative to each other and to plasminogen.

PMID- 7577919
TI  - Cardiac troponin I induced conformational changes in cardiac troponin C as
      monitored by NMR using site-directed spin and isotope labeling.
AB  - Conformational changes in both free cardiac troponin C (cTnC) and in complex with
      a recombinant troponin I protein [cTnI(33-211), cTnI(33-80), or cTnI (86-211)]
      were observed by means of a combination of selective carbon-13 and spin labeling.
      The paramagnetic effect from the nitroxide spin label, MTSSL, attached to
      cTnC(C35S) at Cys 84 allowed measurement of the relative distances to the 13C
      methyl groups of the 10 methionines of cTnC in the monomer or complex. All 10 1H
      13C correlations in the heteronuclear single- and multiple-quantum coherence
      (HSMQC) spectrum of [13C-methyl] Met cTnC in the complex with cTnI(33-211) were
      previously assigned [Krudy, G. A., Kleerekoper, Q., Guo, X., Howarth, J. W.,
      Solaro, R. J., & Rosevear, P. R. (1994) J. Biol. Chem. 269, 23731-23735]. In the
      presence of oxidized spin label, nine of the 10 Met methyl 1H-13C correlations of
      cTnC were significantly broadened in the cTnC(C35S) monomer. This suggests
      flexibility within the central helix, or interdomain D/E helical linker, bringing
      the N- and C-terminal domains in closer proximity than predicted from the
      crystallographic structure of TnC. In the spin-labeled cTnC(C35S). cTnI(33-211)
      complex only N-terminal Met methyl 1H-13C correlations of cTnC(C35S) were
      paramagnetically broadened beyond detection, whereas correlations for Met
      residues (103, 120, 137, and 157) in the C-terminal domain were not. Thus,
      complex formation with cTnI decreases interdomain flexibility and maintains cTnC
      in an extended conformation. This agrees with the recently published study
      suggesting that sTnC is extended when bound to sTnI [Olah, G. A., & Trewhella, J.
      (1994) Biochemistry 33, 12800-12806]. The recombinant N-terminal domain of cTnI,
      cTnI(33-80), gave similar results as observed with cTnI(33-211) when complexed
      with spin-labeled cTnC(C35S). However, complex formation with the C-terminal
      fragment, cTnI(86-211), which contains the inhibitory sequence, is insufficient
      to maintain cTnC extended to the amount observed with either cTnI(33-211) or
      cTnI(33-80); although compared to that observed in free cTnC, it does cause
      decreased flexibility in the interdomain linker. In the absence of the N-terminal
      domain of cTnI, there is a decrease in flexibility within the N-terminal domain
      of cTnC. Interestingly, the N-terminal domain of cTnC in the reduced spin-labeled
      complex with cTnI(86-211), in the presence of ascorbate, showed two distinct
      conformations which were not seen in the complex with cTnI(33-211).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7577918
TI  - Phospholipid binding and lecithin-cholesterol acyltransferase activation
      properties of apolipoprotein A-I mutants.
AB  - Recombinant human apolipoprotein A-I (apo A-I) and three deletion mutants: apo A
      I(delta Leu44-Leu126), apo A-I(delta Glu139-Leu170), and apo A-I(delta Ala190
      Gln243), purified from the periplasmic space of Escherichia coli, were studied.
      The rate of turbidity decrease following mixing of apo A-I(delta Ala190-Gln243)
      with dimyristoylphosphatidylcholine (DMPC) vesicles at 23 degrees C was 10-fold
      lower than that of the other apo A-I proteins, confirming that the carboxy
      terminal region of apo A-I plays a role in rapid lipid binding. The Stokes radii
      of reconstituted high-density lipoproteins (rHDL), containing
      dipalmitoylphosphatidylcholine and cholesterol, were larger for the three apo A-I
      mutants [6.3 nm for apo A-I(delta Leu44-Leu126), 6.1 nm for apo A-I(delta Glu139
      Leu170), and 6.5 nm for apo A-I(delta Ala190-Gln243)] than for intact apo A-I
      (5.0 nm). The mutant rHDL all contained 4 apo A-I molecules per particle as
      compared to 2 for intact apo A-I. Circular dichroism measurements revealed 8
      alpha-helices per apo A-I molecule, 5 per apo A-I(delta Leu44-Leu126), 6 per apo
      A-I(delta Glu139-Leu170), and 4 per apo A-I(delta Ala190-Gln243) molecule as
      compared to predicted values of 8, 5, 6, and 6 alpha-helices,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577921
TI  - Characterization of a cytosolic activity that induces the formation of Golgi
      membrane tubules in a cell-free reconstitution system.
AB  - Using a cell-free reconstitution system, we have characterized a cytosol- and ATP
      dependent process that leads to the formation of membrane tubules from isolated
      Golgi complexes. These membrane tubules are uniform in diameter (50-70 nm) and
      morphologically identical to ones normally seen in cells and to those which are
      enhanced following brefeldin A treatment. Tubulation was strictly dependent on an
      activity present in an organelle-free extract of bovine brain cytosol and
      hydrolyzable ATP. Tubule formation was saturable with respect to both cytosol and
      ATP with half-maximal induction occurring at approximately 0.5 mg/mL cytosol and
      10-20 microM ATP. Mild proteolytic treatment of Golgi membranes significantly
      reduced the extent of tubulation to subsequently added cytosol, suggesting that
      the tubulation activity interacts with Golgi-associated membrane proteins. The
      cytosolic tubulation activity was heat-labile, nondialyzable, and precipitated in
      ammonium sulfate. This activity could be followed through various chromatographic
      steps to yield fractions enriched in a major 40 kDa protein and several other
      minor proteins of approximately 80, 60, and 30 kDa. Monospecific antibodies
      against the 40K protein inhibited the cytosol-dependent tubulation of Golgi
      membranes in the cell-free system. Gel filtration chromatography suggests that
      the tubulation activity has a native molecular weight of approximately 125,000
      140,000. These results establish the existence of cytosolic protein factors that
      regulate the formation of Golgi membrane tubules, and will provide the means for
      a biochemical dissection of membrane tubulation.

PMID- 7577922
TI  - Aging of tubulin monomers using 5,5'-bis(8-anilino-1-naphthalenesulfonate) as a
      probe.
AB  - The fluorescent probe bis(8-anilino-1-naphthalenesulfonate) (bis-ANS) has been
      used to monitor the time- and temperature-dependent aging of tubulin, whereby new
      hydrophobic binding sites of lower affinity are generated on the protein [Prasad,
      A. R. S., et al. (1986a) Biochemistry 25, 739-742]. We carried out a detailed
      analysis of this phenomenon and found that, in addition to antimitotic drugs like
      colchicine or vinblastine, other parameters, viz., low temperature and protein
      stabilizers (e.g., glycerol and sucrose), inhibit the extent of enhanced binding
      of bis-ANS. Moreover, the generation of additional bis-ANS binding sites are also
      suppressed at high concentrations of tubulin. Cleavage of the carboxy-termini of
      tubulin (bound to bis-ANS) by subtilisin causes a significant reduction in the
      enhanced fluorescence, but has no effect on the high-affinity binding site of bis
      ANS. All of these observations can be explained by the correlation of the
      presence of additional binding with the dissociation of heterodimeric tubulin
      into monomers. Enhanced binding of bis-ANS is due to tubulin dimers that have
      undergone dissociation, resulting in a loosening of its tertiary structure with
      the generation of a plethora of hydrophobic sites.

PMID- 7577923
TI  - Microtubule-associated proteins and the flexibility of microtubules.
AB  - Experiments were conducted to learn whether the binding of microtubule-associated
      proteins (MAPs) to microtubules alters the flexibility of the microtubules.
      Flexibility was measured in vitro by two established techniques. The first
      employed measurement of the bending of the microtubule in a flow of buffer; the
      second involved repeated measurement of random thermal fluctuations in the
      microtubule's shape. Similar values were obtained from microtubules prepared from
      purified tubulin and those prepared from microtubule protein containing
      saturating concentrations of MAPs isolated from bovine brain. When measured by
      the flow technique at 37 degrees C and pH 6.9, the persistence length of pure
      tubulin microtubules was found to be 8.4 +/- 2.2 mm and that of MAP-containing
      microtubules was 9.4 +/- 2.7 mm, not significantly different from each other.
      When measured by the thermal fluctuation technique under identical conditions,
      values of 6.2 +/- 0.8 and 6.5 +/- 0.8 mm were obtained, again not significantly
      different from each other. The results show that the binding of MAPs to native
      microtubules in vitro has little or no effect on their flexibility. MAP-induced
      effects on the cytoskeleton observed in vivo are likely to be due to other
      causes, such as formation of microtubule bundles.

PMID- 7577924
TI  - Efficient modulation of glucolipid enzyme activities in membranes of Acholeplasma
      laidlawii by the type of lipids in the bilayer matrix.
AB  - It is generally anticipated, but so far not fully shown, that the physical
      properties of membrane lipid bilayers are governed by the concerted actions of
      the lipid-synthesizing enzymes. In the membrane of Acholeplasma laidlawii a
      constant surface charge density, similar phase equilibria, and a nearly constant
      spontaneous curvature are maintained for the polar lipids. Important for these
      properties are monoglucosyldiacylglycerol (MGlcDAG) and diglucosyldiacylglycerol
      (DGlcDAG), forming mainly reversed nonlamellar and lamellar phases, respectively.
      The syntheses of these lipids (from 1,2-DAG and MGlcDAG) by two consecutively
      acting, membrane-bound glucosyltransferases have been analyzed in synthetic lipid
      bilayers of selected physical properties. Both enzymes demanded the presence of
      activator lipids; for MGlcDAG synthesis a critical fraction of anionic lipids was
      important, whereas for the DGlcDAG synthesis substantial amounts of a liquid
      crystalline phosphatidylglycerol (PG) with a certain chain length were essential.
      The rates of the syntheses for the two glucolipids increased with decreasing
      chain length of the DAG and MGlcDAG substrates. The enzymatic formation of
      DGlcDAG (bilayer-forming) was influenced in a dose-dependent manner by the
      nonbilayer (curvature) propensities of several amphiphilic and hydrophobic lipids
      in two different bilayer matrixes. However, the preceding synthesis of the
      nonlamellar MGlcDAG was only affected to a minor extent by such additives. The
      mechanism for modulation involved an enhancement of the activating potencies of
      PG in a cooperative fashion at physiological concentrations for PG.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577925
TI  - A peptide from the heptad repeat of human immunodeficiency virus gp41 shows both
      membrane binding and coiled-coil formation.
AB  - The envelope glycoprotein gp41 from human immunodeficiency virus type 1 (HIV-1)
      is involved in membrane fusion and virus entry. It contains a functionally
      important leucine zipper-like heptad repeat region (residues 553-590). To
      investigate the solution structure and membrane-binding properties of this
      region, cysteine-substituted variants of a 38-residue peptide derived from the
      heptad repeat were synthesized and modified with nitroxide spin labels.
      Analytical equilibrium ultracentrifugation studies indicated it is primarily
      tetrameric in solution, in contrast to the protein gp160 which is a mixture of
      trimers and tetramers. Electron paramagnetic resonance (EPR) measurements
      indicated that the peptide was bound to vesicles containing 10 mol % negatively
      charged lipids. The peptides were bound parallel to the membrane surface, near
      the water-membrane interface, in a structure different from the solution
      structure, most likely as monomers. When Asp, Pro, or Ser was substituted for Ile
      at the core "a" position of the heptad repeat in the middle of the peptide, the
      coiled coil was destabilized. In addition, these peptides showed reduced membrane
      binding affinities. Thus, mutations that destabilized coiled-coil formation also
      decreased membrane-binding propensity. These experimental results, taken with
      previous evidence, suggest two functions for the heptad repeat of gp41 after CD4
      binding: (1) to form an extended coiled coil; (2) to provide a hydrophobic face
      that binds to the host-cell membrane, bringing the viral and cellular membranes
      closer and facilitating fusion.

PMID- 7577926
TI  - Purification, characterization, and cloning of a heme-binding protein (23 kDa) in
      rat liver cytosol.
AB  - A heme-binding protein (designated HBP23) has been purified from rat liver
      cytosol using heme-affinity chromatography and either reverse-phase high
      performance liquid chromatography or sequential ion-exchange chromatography. The
      protein (23 kDa) binds heme with an affinity (Kd = 55 nM) higher than that of the
      abundant cytosolic heme-binding proteins, heme-binding protein (HBP)/liver fatty
      acid-binding protein (L-FABP) and the glutathione S-transferases (GSTs) (Kd = 100
      200 nM). HBP23 is present in the cytosol of liver, kidney, spleen, small
      intestine, and heart, with the liver showing the highest content. A cDNA coding
      the 23-kDa protein was cloned using reverse transcription polymerase chain
      reaction with degenerative oligonucleotides derived from partial amino acid
      sequences. The cloned cDNA encoded 199 amino acids, and its amino acid sequence
      showed no homology to HBP/L-FABP, GSTs, or any other heme-binding proteins or
      hemeproteins. Homology search showed that HBP23 is highly homologous to mouse
      macrophage 23-kDa stress protein, which is inducible by oxidant stress in
      peritoneal macrophages [Ishii, T., Yamada, M., Sato, H., Matsue, M., Taketani,
      S., Nakayama, K., Sugita, Y., and Bannai, S. (1993) J. Biol. Chem. 268, 18633
      18636]. Thioredoxin peroxidase as well as HBP23 and the mouse macrophage 23-kDa
      stress protein are members of the peroxiredoxin family, a recently recognized
      class of antioxidant proteins [Chae, H. Z., Chung, S. J., & Rhee, S. G. (1994) J.
      Biol. Chem. 269, 27670-27678]. An increase in HBP23 mRNA was observed in Hepa 1-6
      cells after treatment with heme and cadmium and during liver regeneration after
      partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577927
TI  - Expression of the mRNA of heme-binding protein 23 is coordinated with that of
      heme oxygenase-1 by heme and heavy metals in primary rat hepatocytes and hepatoma
      cells.
AB  - A 23-kDa protein with high affinity for heme (KD = 55 nM), therefore termed heme
      binding protein 23 kDa (HBP23), was purified from rat liver cytosol [Iwahara, S.,
      et al. (1995) Biochemistry 34, 13398-13406]. Homology search of the cloned HBP23
      cDNA revealed that this protein belongs to a recently recognized class of thiol
      peroxidases, the antioxidant peroxiredoxin family. Since HBP23 gene expression
      was highest in the liver, HBP23 mRNA regulation by heme and heavy metals was
      investigated in cultures of primary rat hepatocytes and mouse hepatoma Hepa 1-6
      cells. In both cell cultures HBP23 mRNA levels were upregulated in a time- and
      dose-dependent manner by heme. Heme-dependent induction of HBP23 mRNA occurred
      coordinately with that of the heme-metabolizing enzyme heme oxygenase-1, which
      was recently identified as inducible by oxidative stress. Treatment of primary
      rat hepatocyte or hepatoma cell cultures with the heavy metals CdCl2 (10 microM)
      and CoCl2 (300 microM) induced in parallel HBP23 and HO-1 mRNA levels, in the
      case of CdCl2 to even higher levels than heme. By contrast, mRNA expression of
      another heme binding protein, hemopexin, was not induced in hepatocyte cell
      cultures by heme or heavy metals. The data suggest that the expression of HBP23
      and HO-1 mRNA is regulated by (a) similar mechanism(s) in liver and that both
      genes could play a common physiological role as antioxidants and/or in heme
      metabolism.

PMID- 7577928
TI  - Identification of Asn289 as a ligand binding site in the rat thyrotropin
      releasing hormone (THR) receptor as determined by complementary modifications in
      the ligand and receptor: a new model for THR binding.
AB  - To test the hypothesis that pGlu of the thyrotropin-releasing hormone (TRH, pGlu
      His-ProNH2) binds to Asn289 in the third extracellular loop (EL3) of its receptor
      through a hydrogen bonding interaction, we converted Asn289 to Asp (N289D mutant)
      and measured the potencies of TRH and Pro1TRH for the wild-type and mutant
      receptors. TRH was 100 times less potent for the N289D receptor than for the wild
      type. In contrast, Pro1TRH, which has a protonated proline in place of the pGlu
      of TRH, was 10 times more potent for the N289D receptor than for the wild-type. A
      similar result was obtained when Asn289 was converted to Glu, while the potency
      of Pro1TRH did not change when Asn289 was converted to Ala, confirming that the
      increased potency of Pro1TRH for the N289D receptor was due to a charge
      interaction between Pro1TRH and the mutant receptor. These findings are
      inconsistent with a previous model indicating a direct interaction of the pGlu of
      TRH with Asn110 in the third transmembrane helix of the receptor (Perlman et al.
      (1994) J. Biol. Chem. 269, 23383-23386). When Asn110 was converted to Asp (N110D
      mutant), unlike the N289D receptor, the potency of Pro1TRH for the N110D receptor
      was decreased by > 10-fold rather than increased. Therefore, a direct interaction
      of Asn110 with the pGlu of TRH could not be supported by our experiments. We
      propose a new model in which the pGlu of TRH binds to Asn289 in EL3 and conclude
      that, unlike catecholamines which bind completely within the transmembrane domain
      of their receptors, this tripeptide binds, at least in part, to the extracellular
      domain of its receptor.

PMID- 7577929
TI  - Role of the carboxyl terminal MATEE sequence of spermidine/spermine N1
      acetyltransferase in the activity and stabilization by the polyamine analog
      N1,N12-bis(ethyl)spermine.
AB  - Purified recombinant spermidine/spermine N1-acetyltransferase (SSAT) was found to
      be unstable in the absence of polyamines, but the loss of activity could be
      prevented or reversed by the addition of the polyamine analog and potential
      antitumor agent N1,N12-bis(ethyl)spermine (BE-3-4-3), which is known to be a
      potent inducer of SSAT in mammalian cells. Addition of BE-3-4-3 prevented the
      loss of SSAT activity and the digestion of the protein by the proteases trypsin,
      Lys-C, or Glu-C. In the absence of BE-3-4-3, this digestion occurred at the
      sequence Lys141Arg142Arg143 for trypsin or Lys-C and at the sequence Glu151Glu152
      for Glu-C. When these sites were altered by mutation to residues which are not
      substrates for these proteases, cleavage in the absence of BE-3-4-3 occurred at
      residues Lys161, Lys166, and Glu162. These results indicate that the structure of
      SSAT contains a region that binds to the polyamine analog, BE-3-4-3, and that
      binding alters the configuration of the protein to prevent protease access to the
      region from amino acid residue 141 to the carboxyl terminal end (residue 171) of
      the SSAT. In order to determine the nature of the regulatory sites, specific
      mutations were made in the SSAT amino acid sequence, and the activity of the
      resulting SSAT protein and the sensitivity to proteases in the presence and
      absence of BE-3-4-3 was determined. The results indicate that the carboxyl
      terminal domain, MATEE, is critical for activity and for protection by BE-3-4
      3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577930
TI  - Domain organization and a protease-sensitive loop in eukaryotic ornithine
      decarboxylase.
AB  - Trypanosoma brucei ornithine decarboxylase was reconstituted by coexpression of
      two polypeptides corresponding to residues 1-305 and residues 306-425 in
      Escherichia coli. The two peptides were coexpressed, at wild-type levels, from a
      single transcriptional unit that was separated by a 15-nucleotide untranslated
      region containing a ribosome binding site. The fragmented enzyme was purified and
      analyzed. The N- and C-terminal peptides are tightly associated into a fully
      active tetramer which has the same molecular weight as the native dimer. The
      kinetic constants (Km and kcat) measured for the decarboxylation of ornithine are
      identical to those obtained for the wild-type enzyme. These results suggest that
      the enzyme is organized into two structural domains, with a domain boundary in
      the region of amino acid 305. In contrast, the individual N- and C-terminal
      peptides are expressed primarily as inclusion bodies. Small quantities of soluble
      N-terminal peptide could be purified. This truncated protein is capable of
      inhibiting the wild-type enzyme, suggesting that it is folded into a native-like
      structure. Limited proteolysis with trypsin or chymotrypsin identifies a likely
      surface loop at amino acids 160-170, present in both the mouse and T. brucei
      enzyme, which positions one or more functionally important active site residues
      (e.g., Lys169). Kinetic analysis of a chimeric enzyme composed of T. brucei and
      mouse ornithine decarboxylase suggests that the substrate carboxylate binding
      determinant is located between residues 1 and 170.

PMID- 7577931
TI  - E461H-beta-galactosidase (Escherichia coli): altered divalent metal specificity
      and slow but reversible metal inactivation.
AB  - beta-galactosidase (Escherichia coli) with a His substituted for Glu-461 retained
      about 10% of its normal activity in the absence of divalent metals but was
      inactivated rather than activated by Mg2+, Mn2+, Zn2+, Ni2+, Cu2+, and Co2+.
      Since Zn2+, Ni2+, Cu2+, and Co2+ do not interact with wild type beta
      galactosidase while Mg2+ and Mn2+ activate and Ca2+ binds but has no effect on
      wild type beta-galactosidase activity, the substituted enzyme has very different
      divalent metal interactions. A much larger amount of Mg2+ than of the other
      divalent metal ions was needed to inactivate the substituted enzyme at pH 7 (half
      maximal activity was at 12.5 mM Mg2+ while the half-maximal activities with the
      other metals were at micromolar levels) compared to the amount of Mg2+ needed to
      activate the wild type enzyme. The inactivation of E461H-beta-galactosidase
      caused by Mg2+ took about 20 min. Reactivation by removal of the divalent metal
      took about 60 min. Interaction with Mg2+ was about 10(7)-fold stronger at pH 9
      than at pH 7, and inactivation occurred in less than 2 min at higher pH values.
      "Galactosylation" (k2, cleavage of the glycosidic bond) seemed to be rate
      limiting for E461H-beta-galactosidase at pH values above 6 with both o
      nitrophenyl beta-D-galactopyranoside and p-nitrophenyl beta-D-galactopyranoside
      in both the presence and absence of Mg2+. Mg2+ caused decreases (about 50-fold)
      of the k2 values of E461H-beta-galactosidase (apparent pKa was about
      6.8).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577932
TI  - Thiol dependence of nitric oxide synthase.
AB  - Nitric oxide synthases (NOS) require NADPH and tetrahydrobiopterin (H4biopterin)
      to convert L-arginine to L-citrulline. The additional requirement and effects of
      thiols during purification and activity assays of NOS are unclear; for example,
      glutathione (GSH) has been reported to stimulate or, in the presence of catalase,
      to inhibit enzyme activity. We therefore studied the effects of different thiols,
      thiol reagents, antioxidants, and H4biopterin-regenerating systems on purified
      porcine cerebellum NOS. GSH in the presence of catalase did not inhibit NOS. In
      contrast, GSH and, to a lesser degree, several other thiols consistently
      stimulated total L-arginine turnover up to 4-fold. In the presence of GSH, Vmax
      of NOS was increased, the usually observed loss of activity during the 15 min
      assay was less dramatic, and the apparent S0.5 value for H4biopterin decreased.
      Stabilization of NOS activity by GSH was augmented by protein disulfide isomerase
      (PDI), indicating that, at least in part, GSH acted by reductive protection of
      NOS protein thiols. Consistent with this, four different protein thiol reagents
      abolished NOS activity. In other experiments, specific allosteric binding was
      excluded as a potential mechanism of GSH regulation of NOS. In addition, GSH may
      affect NOS kinetics by recycling or preventing the autoxidation of H4biopterin.
      In support of this, the non-thiol reductant ascorbate and dihydropteridine
      reductase mimicked the effects of GSH on NOS kinetics, but not on NOS stability.
      Thus, NOS activity depends on both H4biopterin and the reduced state of essential
      protein thiols.

PMID- 7577933
TI  - Mechanism of time-dependent inhibition of 5 alpha-reductases by delta 1-4
      azasteroids: toward perfection of rates of time-dependent inhibition by using
      ligand-binding energies.
AB  - Finasteride (17 beta-N-tert-butylcarbamoyl-4-aza-5 alpha-androstan-1-en-3- one)
      is a time-dependent, apparently irreversible inhibitor of 5 alpha-reductases, but
      does not fully inhibit the activity of 5 alpha-reductase in vivo. This limited
      efficacy has been attributed to its slow rate of inhibition against the type-1
      isozyme [Tian, G. (1995) J. Pharm. Sci. (in press)]. Here the feasibility of
      increasing the rate of inhibition of 5 alpha-reductases by providing binding
      energies with the inhibitor at a site remote from the center of chemical
      transformation was explored. Substitution of N-(2,5-bis(trifluoromethyl)phenyl)
      group, which had been shown to benefit 6-azasteroids in the binding to 5 alpha
      reductases [Frye, S., Haffner, C. D., Maloney, P. R., Hiner, R. N., Unwalla, R.
      J., Batchelor, K. W., Bramson, H. N., Stuart, J. D., Schweiker, S. L., Van
      Arnold, J., Bickett, D. M., Moss, M. L., Tian, G., Lee, F. W., Tippin, T. K.,
      James, M. K., Grizzle, M. K., Long, J. E., & Croom, D. K. (1995) J. Med. Chem.
      38, 2621-2627], for the N-tert-butyl substituent at C-17 of finasteride did not
      perturb the mechanism of inhibition but significantly increased the rate of
      inhibition of type-1 5 alpha-reductase. The rate of inhibition was too fast to
      determine accurately when the normal substrate testosterone was used in the
      progress curve analysis as this inhibition rate is approaching the value of
      kcat/Km for the enzyme reaction.

PMID- 7577934
TI  - Preparation and characterization of a truncated form of phthalate dioxygenase
      reductase that lacks an iron-sulfur domain.
AB  - Phthalate dioxygenase reductase (PDR) is the electron transferase component of
      the phthalate dioxygenase system. It is a modular enzyme consisting of distinct
      iron-sulfur, flavin mononucleotide (FMN) and pyridine nucleotide binding domains.
      We have taken advantage of this modularity and removed the 10-kDa iron-sulfur
      domain by selective proteolytic cleavage between residues N229 and T230 in a
      solvent-accessible peptide that links the iron-sulfur and pyridine nucleotide
      binding domains. The resulting PDR(-FeS) has a molecular weight of 25,792 +/- 10
      and the same amino terminus as the native PDR. It has spectral features that are
      very similar to the flavin component of the PDR absorbance spectrum. Remarkably,
      despite the magnitude of this structural modification, the kinetic, redox, and
      pyridine nucleotide binding properties of PDR(-FeS) are very similar to those
      reported for PDR [Gassner, G., et al. (1994) Biochemistry 33, 12184-12193]. The
      principal mechanistic feature distinguishing PDR(-FeS) from PDR is the inability
      of the attenuated enzyme to carry out intramolecular electron transfer. The
      reaction of PDR(-FeS) with NADH consists of binding and the formation of an
      initial Michaelis complex (MC-1') (Kd approximately 25 microM), isomerization of
      the enzyme (120 s-1) to form a charge-transfer complex with FMN (CT-1'), hydride
      transfer to the FMN (76 s-1) with formation of a second charge-transfer complex
      (CT*'), and finally release of nicotinamide adenine dinucleotide (NAD) (58 s-1)
      from the reduced enzyme. The rate of NAD release from PDR(-FeS) is nearly the
      same as the rate of NAD release and intramolecular electron transfer in the
      reductive half-reaction of PDR, which supports the idea that the release of NAD
      triggers intramolecular electron transfer in PDR. The midpoint potential of the
      oxidized/semiquinone couple of PDR(-FeS) (-170 mV) is the same as the value
      measured for PDR. A value of -235 mV is measured for the midpoint potential of
      the semiquinone/hydroquinone couple of PDR(-FeS), which is approximately 50 mV
      more positive than the PDR2e-/PDR3e- redox couple at pH 7. NAD binds to PDR(-FeS)
      about 20-fold more weakly than does NADH; the enzyme redox state has no
      significant influence on pyridine nucleotide binding affinity.

PMID- 7577935
TI  - Identification of an essential cysteinyl residue in the ArsC arsenate reductase
      of plasmid R773.
AB  - The ArsC protein encoded by the arsenical resistance operon of plasmid R773
      catalyzes the reduction of arsenate to arsenite in Escherichia coli. The
      reductase has been shown to require glutathione and glutaredoxin, suggesting that
      thiol chemistry might be involved in the reaction mechanism. The ArsC arsenate
      reductase has two cysteinyl residues, Cys12 and Cys106. By a combination of
      random and site-specific mutagenesis, Cys12 was altered to four other amino acid
      residues. Cells expressing any of those arsC genes were sensitive to arsenate.
      The ArsCC12S protein was purified and found to be catalytically inactive. Cys106
      was altered separately to seryl, glycyl, and valyl residues. Cells expressing
      arsCC106S, arsCC106G, and arsCC106V genes retained arsenate resistance, and the
      purified C106S and C106G proteins had reductase activity. Both wild-type ArsC and
      C106S proteins were inactivated by iodoacetate. In the native enzyme only Cys12
      was alkylate by iodoacetate; Cys106 was alkylated only if the enzyme was first
      denatured. In the presence of the substrate, arsenate, or competitive inhibitors,
      phosphate or sulfate, the rate of alkylation was reduced. Reductase activity was
      inhibited by N-ethylmaleimide and could be protected by arsenate. These results
      suggest Cys12 is an active-site residue essential for catalysis by the arsenate
      reductase.

PMID- 7577936
TI  - Identification of residues in the aromatic substrate binding site of horseradish
      peroxidase by 1H NMR studies on isozymes.
AB  - The cyanide-inhibited complexes of two horseradish peroxidase acidic isozymes, A1
      (HRPA1, unsequenced) and A2 (HRPA2, sequenced), have been examined by solution
      two-dimensional 1H NMR methods, and the active site molecular and electronic
      structure compared to that of the well-characterized isozyme C (HRPC) (Chen, Z.,
      de Ropp, J.S., Hernandez, G., & La Mar, G.N. (1994) J. Am. Chem. Soc. 116, 8772
      8783), as well as to that of cytochrome c peroxidase. The identity and alignment
      of catalytically relevant residues near the active site for HRPA1-CN and HRPA2-CN
      are determined, and key residue replacements implicated in the differential
      catalytic properties of the acidic vs C isozymes are identified. Heme and axial
      His contact shift patterns, as well as dipolar contacts of residues with the heme
      and with each other, confirm a highly conserved structure among the three
      isozymes, including for the distal pocket residues involved in the activation of
      the enzyme. The remarkable dynamic stability of the heme pocket, as reflected in
      NH exchange with solvent, is also conserved for the three isozymes. An additional
      heme contact, Ile 148, is identified in HRPC-CN. Four residues in contact with
      the heme in HRPC-CN are replaced in HRPA2-CN, two of which are likely
      functionally neutral, Gly 169-->Ala and Ile 148-->Leu. However, two substitutions
      in the acidic isozymes in the aromatic substrate binding pocket on the heme edge,
      Ile 244-->Leu and Phe 179 or 221-->aliphatic residue, could well account for the
      dramatic decrease (approximately 10(3) in aromatic substrate binding in the A1
      and A2 isozymes vs the C isozyme of HRP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577937
TI  - Effect of the His175-->Glu mutation on the heme pocket architecture of cytochrome
      c peroxidase.
AB  - Resonance Raman (RR) and electronic absorption spectra of the ferric and ferrous
      forms of the His175Glu mutant of cytochrome c peroxidase are reported. At 296 K,
      the FeIII form is five-coordinate high spin and the resonance Reman spectra are
      very similar to those obtained for the wild type enzyme, even though in the
      mutant the Fe atom is bound to an oxygen atom of the Glu residue. The only
      difference is that the bands due to the out-of-plane modes are very weak,
      indicating a less distorted heme plane compared to CCP. The absorption spectrum
      is similar to that of CCP, as far as the Soret and alpha, beta bands are
      concerned, but the charge-transfer band due to the a2u(pi)-->eg(d pi) transition
      is 8 nm blue-shifted relative to that of the wild type enzyme, indicating that a
      more negative ligand is bound to the heme iron. As the temperature is lowered,
      the five-coordinate heme converts to a six-coordinate high-spin form. The
      conversion is readily reversible. A temperature effect on the protein structure
      is proposed that permits the Fe atom to approach the heme plane and to bind the
      distal water molecule. The results are discussed in terms of the X-ray structure,
      which shows a different disposition of the distal water molecules in the Glu175
      mutant. The RR spectra also show that the heme is more contracted and distorted
      at 19 K than at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577938
TI  - Methionine-393 is an axial ligand of the heme b558 component of the cytochrome bd
      ubiquinol oxidase from Escherichia coli.
AB  - The cytochrome bd oxidase is one of two terminal oxidases in the aerobic
      respiratory chain of Escherichia coli. The complex is composed of two subunits (I
      and II) and three heme prosthetic groups (heme b558, heme b595, and a chlorin,
      called heme d). Both subunits are located within the bacterial cytoplasmic
      membrane, and each has multiple putative transmembrane helices. Heme b558 is a
      six-coordinate, low-spin heme component of the oxidase which has been shown to be
      contained within subunit I and has been implicated in the oxidation of the
      substrate, ubiquinol-8, in the cytoplasmic membrane. Previous site-directed
      mutagenesis studies identified His186, predicted to be near the periplasmic side
      of transmembrane helix D of subunit I, as one of the axial ligands of heme b558.
      Since mutagenesis of none of the other histidines in subunit I perturbs heme
      b558, it was concluded that this heme cannot have bis(histidine) ligation. In
      this work, the properties of 14 mutants are reported, including substitutions for
      each of 10 methionine residues within subunit I. Among this set of mutants, only
      the replacement of M393 perturbs heme b558. Replacement of M393 by leucine
      results in the conversion of heme b558 to a high-spin state. Surprisingly, the
      M393L mutation does not eliminate enzymatic activity, and the mutant oxidase has
      sufficient turnover to support aerobic growth of the cells. The addition of
      imidazole to the purified M393L oxidase converts heme b558 back to a low-spin
      configuration. The data strongly suggest that the sixth axial ligand of heme b558
      is methionine-393, and that this heme, therefore, has histidine-methionine
      ligation. The results are consistent with recent cryogenic near-infrared magnetic
      circular dichroism spectra that also indicate histidine-methionine ligation of
      heme b558.

PMID- 7577939
TI  - Influence of the 9-methyl group of the retinal on the photocycle of
      bacteriorhodopsin studied by time-resolved rapid-scan and static low-temperature
      Fourier transform infrared difference spectroscopy.
AB  - The photocycle of bacteriorhodopsin (BR) regenerated with all-trans-9
      demethylretinal was investigated by time-resolved rapid-scan Fourier transform
      infrared difference spectroscopy, by static low-temperature difference
      spectroscopy at 80, 170, and 213 K and by static steady-state difference
      spectroscopy at 278 K. In addition, the formation and decay of M intermediate was
      monitored at 412 nm with conventional flash photolysis experiments. Our data show
      that the removal of the 9-methyl group strongly changes the photocycle of BR. The
      reaction cycle is slowed down about 250-fold. The photoreaction is characterized
      by a slow rise of the M intermediate and by a very long-lived N intermediate. No
      O intermediate could be observed. The low-temperature spectra indicate that
      already at 80 K a KL-like photoproduct is formed. L can be obtained as in native
      BR at 170 K, but its decay appears to be inhibited, since it can still be
      observed at 213 K and high pH, in addition to the M intermediate. As in native
      BR, the 15-hydrogen out-of-plane modes of the L and N intermediates (observed in
      2H2O) are very similar. Evidence for the existence of three N substates which
      differ in the protonation state of Asp96 and in the amide I bands is presented.
      This is explained by the extremely slowed-down reisomerization of the
      chromophore. The results are discussed with respect to alterations in the
      chromophore-protein interaction, caused by the removal of the 9-methyl group.

PMID- 7577940
TI  - Calcium modulates the photoassembly of photosystem II (Mn)4-clusters by
      preventing ligation of nonfunctional high-valency states of manganese.
AB  - The requirement for Ca2+ in the Mn(2+)-dependent photoactivation of oxygen
      evolution was re-evaluated using 17 kDa/24 kDa-less photosystem II (PSII)
      membranes depleted of (Mn)4-clusters by NH2OH extraction. At optimum conditions
      (1 mM Mn2+/10 microM 2,6-dichlorphenolindophenol (DCIP)/20 mM Ca2+), the light
      induced increase of oxygen-evolution activity, the increase of membrane-bound Mn,
      and the B-band thermoluminescence emission intensity occurred in parallel. The
      extent of recovery of the oxygen-evolution activity was equivalent to 88% and 66%
      of the activity shown by parent NaCl-extracted PSII membranes and by PSII
      membranes, respectively. Neither photodamage of primary electron transport nor
      photoligation of nonfunctional Mn > or = 3+ occurred. Analyses of the Ca2+
      concentration dependence for the maximum recovery of oxygen evolution activity
      gave evidence for Ca(2+)-binding site(s) having Km values of approximately 38 and
      approximately 1300 microM. Illumination of membranes in the strict absence of
      Ca2+ resulted in large increases (up to 18 Mn/200 chlorophyll) of EDTA
      nonextractable, EPR silent, nonfunctional membrane-bound Mn > or = 3+ and small
      increases of oxygen-evolution capability, dependent on pH and concentrations of
      Mn2+ and DCIP. No photodamage of primary electron transport and only
      approximately 17% decrease of AT-band thermoluminescence occurred during the
      photoligation of the Mn > or = 3%. In the strict absence of Ca2+, significant
      recovery of oxygen-evolution activity was obtained under a limited set of
      conditions permitting photoligation of a limited abundance of the nonfunctional
      Mn > or = 3+. Small (NH2-OH, H2O2) as well as bulky external reductants readily
      reduced and dissociated the Mn > or = 3+ from the membranes. Reillumination of
      these membranes under optimal conditions for photoactivation (plus Ca2+) gave a
      high yield of (Mn)4-clusters and oxygen-evolution capability. Similarly, simple
      addition of Ca2+ to membranes containing nonfunctional Mn > or = 3+ followed by
      reillumination resulted in the conversion of Mn > or = 3+ to (Mn)4-clusters. It
      is argued that Ca2+ promotes the conformational change involved in the conversion
      of the Mn2+ mononuclear intermediate to the Mn(3+)-Mn2+ binuclear intermediate in
      the photoactivation mechanism, thereby permitting photoassembly of (Mn)4-clusters
      and preventing photo-inactivation by Mn > or = 3+ ions.

PMID- 7577941
TI  - Comparison of lethal and nonlethal transthyretin variants and their relationship
      to amyloid disease.
AB  - The role that transthyretin (TTR) mutations play in the amyloid disease familial
      amyloid polyneuropathy (FAP) has been probed by comparing the biophysical
      properties of several TTR variants as a function of pH. We have previously
      demonstrated that the partial acid denaturation of TTR is sufficient to effect
      amyloid fibril formation by self-assembly of a denaturation intermediate which
      appears to be monomeric. Earlier studies on the most pathogenic FAP variant
      known, Leu-55-Pro, revealed that this variant is much less stable toward acid
      denaturation than wild-type TTR, apparently explaining why this variant can form
      amyloid fibrils under mildly acidic conditions where wild-type TTR remains
      nonamyloidogenic. The hypothesis that FAP mutations destabilize the TTR tetramer
      in favor of a monomeric amyloidogenic intermediate under lysosomal (acidic)
      conditions is further supported by the data described here. We compare the acid
      stability and amyloidogenicity of the most prevalent FAP variant, Val-30-Met,
      along with the double mutant, Val-30-Met/Thr-119-Met, which serves to model the
      effects of these mutations in heterozygous patients where the mutations are in
      different subunits. In addition, we have characterized the Thr-119-Met TTR
      variant, which is a common nonpathogenic variant in the Portuguese population, to
      further investigate the role that this mutation plays in protecting individuals
      who also carry the Val-30-Met mutation against the classically severe FAP
      pathology. This biophysical study demonstrates that Val-30-Met TTR is
      significantly less stable toward acid denaturation and more amyloidogenic than
      wild-type TTR, which in turn is less stable and more amyloidogenic than Thr-119
      Met TTR. Interestingly, the double mutant Val-30-Met/Thr-119-Met is very similar
      to wild-type TTR in terms of its stability toward acid denaturation and its
      amyloidogenicity. The data suggest that the Thr-119-Met mutation confers
      decreased amyloidogenicity by stabilizing tetrameric TTR toward acid
      denaturation. In addition, fluorescence studies monitoring the acid-mediated
      denaturation pathways of several TTR variants reveal that the majority exhibit a
      plateau in the relative fluorescence intensity over the amyloid-forming pH range,
      i.e., ca. pH 4.3-3.3. This intensity plateau suggests that the amyloidogenic
      intermediate(s) is (are) being observed over this pH range. The Thr-119-Met
      variant does not exhibit this plateau presumably because the amyloidogenic
      intermediate(s) do(es) not build up in concentration in this variant. The
      intermediate is undoubtedly forming in the Thr-119-Met variant, as it will form
      amyloid fibrils at high concentrations; however, the intermediate is only present
      at a low steady-state concentration which makes it difficult to detect.

PMID- 7577942
TI  - A novel series of amphiphilic imidazolinium compounds for in vitro and in vivo
      gene delivery.
AB  - We have developed three catioinic amphiphiles based on the structure 1-[2
      (acyloxy)ethyl]-2-alkyl(alkenyl)-3-(2-hydroxyethyl)imidazolinium chloride.
      Although these three compounds differ only in the structure of the hydrophobic
      acyl chains, they differ greatly in their ability to mediate in vivo and in vitro
      gene delivery. Moreover, in vitro efficiency is not predictive of in vivo
      efficiency. The myristoyl form is the most effective compound in vitro, and the
      oleoyl form is the most effective compound in vivo. The compounds readily form
      suspensions in aqueous media, both in the pure form and as mixtures with either
      cholesterol or dioleoylphosphatidylethanolamine. These suspensions can be
      sonicated to produce smaller particles. Particle size, electron microscopy, and
      the ability to capture glucose suggest that these lipids form liposomes on
      suspension in aqueous media. When mixed with plasmid DNA, the lipid particles
      appear to fuse and form larger particles. Fusion is maximal at the critical
      DNA:lipid ratio where extensive aggregation and precipitation are observed.
      Therefore, these compounds behave similarly to other cationic liposome-forming
      lipids upon interaction with DNA.

PMID- 7577943
TI  - The major, N2-Gua adduct of the (+)-anti-benzo[a]pyrene diol epoxide is capable
      of inducing G-->A and G-->C, in addition to G-->T, mutations.
AB  - Mutations induced by the (+)-anti-diol epoxide of benzo[a]pyrene [(+)-anti
      B[a]PDE] were collected in the supF gene of the Escherichia coli plasmid pUB3.
      pUB3 was reacted with (+)-anti-B[a]-PDE and then either (1) transformed
      immediately into E. coli or (2) heated at 80 degrees C for 10 min and then cooled
      prior to transformation--the latter to probe mechanism [Rodriguez & Loechler
      (1993) Biochemistry 32, 1759]. Qualitatively, heating did not affect the
      mutagenic pattern, except at the major base substitution hotspot in supF, G115,
      where principally G-->T mutations were obtained prior to heating, while after
      heating, G-->A and G-->C mutations became statistically significantly more
      prevalent. Several studies have suggested that a heat-induced chemical
      transformation of a (+)-anti-B[a]PDE adduct at G115 (e.g., into an apurinic site)
      is not likely to explain the change in mutational pattern. The most likely model
      is that (+)-anti-B[a]P-N2-Gua is initially trapped in a metastable conformation
      giving principally G-->T mutations, while heating induces a change to a stable
      conformation(s) resulting in G-->T, A, and C mutations. This suggests that adduct
      conformational complexity is at the root of adduct mutational complexity. To
      investigate this model, a plasmid (B[a]P-G115-pRE1) with (+)-anti-B[a]P-N2-Gua in
      the G115 sequence context is constructed using adduct site-specific
      techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577944
TI  - The leucine zippers of the HLH-LZ proteins Max and c-Myc preferentially form
      heterodimers.
AB  - c-Myc and Max are members of a subfamily of the helix-loop-helix transcription
      regulating proteins. Their function is mediated by switches in the dimerization
      partners; c-Myc does not homodimerize in vivo but competes with Mad, another
      member of the subfamily, to form heterodimers with Max, leading to either
      activation or repression of transcription. Max is also able to form homodimers.
      In an attempt to identify which regions of the proteins carry the information to
      determine specific recognition of the dimerization partner, we have investigated
      the dimerization properties of synthetic peptides corresponding to the leucine
      zipper sequence of Max and c-Myc using circular dichroism and nuclear magnetic
      resonance techniques. We show that the heterodimer is obtained readily by simply
      mixing the peptides and that at neutral pH it is more stable than the homodimer
      of the Max leucine zipper. We have shown in a previous paper [Muhle-Goll, C. et
      al. (1994) Biochemistry 33, 11296-11306] that the leucine zipper of c-Myc does
      not form stable homodimers under these conditions. Thus, the leucine zipper
      regions of these two proteins by themselves display the same behavior as the
      entire proteins. However, even the heterodimer is less stable than dimers of
      leucine zippers of the basic leucine zipper family such as GCN4 and Fos-Jun. The
      specificity of the interaction between different monomers can be explained by
      polar interactions. We investigate the structural role of the polar and charged
      residues in the hydrophobic interface by molecular-modeling studies.

PMID- 7577945
TI  - Subunit III of cytochrome c oxidase influences the conformation of subunits I and
      II: an infrared study.
AB  - The secondary structure of wild-type Paracoccus denitrificans cytochrome c
      oxidase obtained by decomposition of the infrared amide I band contains 44% alpha
      helix, 18% beta-sheet, 14% beta-turns, 18% loops, and 6% nonordered segments. The
      mutant lacking subunit III presents a small but significant increase (from 18% to
      24%) in the percentage of loops and slight differences in the other components.
      Using band/area ratios and tyrosine side chain absorption as an inner standard,
      it is shown that in the absence of subunit III the structure of subunits I and II
      is altered although no changes in their alpha-helix or beta-sheet content are
      observed. In the bacterial oxidase, thermal infrared studies show a complex
      denaturation pattern characterized by the presence of a partially denatured
      intermediate state. Of the seven predicted subunit III alpha-helices, only four
      are resistant toward the thermal challenge and behave as expected for typical
      transmembrane helices. The observation that the absence of subunit III influences
      the conformation of loop regions in the two other subunits suggests that part of
      the interaction surface between subunit III and the catalytic subunits might be
      located outside the lipid bilayer.

PMID- 7577946
TI  - NMR solution structure of a nonanucleotide duplex with a dG mismatch opposite a
      10S adduct derived from trans addition of a deoxyadenosine N6-amino group to (+)
      (7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene: an
      unusual syn glycosidic torsion angle at the modified dA.
AB  - A nonanucleotide, d(G1G2T3C4[BaP]A5C6G7A8G9), in which (+)-(7R,8S,9S,10R)-7,8
      dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (7-hydroxyl group and
      epoxide oxygen are trans) is covalently bonded to the exocyclic N6-amino group of
      deoxyadenosine (dA5) through trans addition at C10 of the epoxide (to give a 10S
      adduct) has been synthesized. The solution structure of the duplex,
      d(G1G2T3C4[BaP]A5C6G7A8G9).d(C10T11C12G13G14G15A16C17C18+ ++), containing a dG
      mismatch opposite the modified dA (designated 10S-[BaP]dA.dG 9-mer duplex) has
      been investigated using a combination of 1D and 2D (including COSY, PECOSY,
      TOCSY, NOESY, and indirect detection of 1H-31P HETCOR) NMR spectroscopies. The
      NMR results together with restrained molecular dynamics/energy minimization
      calculations show that the modified dA5 adopts a syn glycosidic torsion angle
      whereas all other nucleotide residues adopt anti glycosidic torsion angles. The
      sugar ring of dA5 is in the C3'-endo conformation, and the sugar rings of the
      other residues are in the C2'-endo conformation. The hydrocarbon attached at dA5
      orients toward the 3' end of the modified strand (i.e., dC6 direction) and
      intercalates between and parallel to bases of dG13 and dG14 of the complementary
      strand directly opposite dC6 and dA5, respectively. The edge of the hydrocarbon
      bearing H11 and H12 is positioned between the imino protons of dG13 and dG14 in
      the interior of the duplex, whereas H4 and H5 at the opposite edge are positioned
      near the sugar H1' and H2" protons of dG13 and facing the exterior of the duplex.
      The mismatched AG base pair is stabilized by dAsyn-dGanti base pairing in which
      the imino proton and the O6 of dG14 are hydrogen bonded to N7- and the single N6
      amino proton, respectively, of the modified dA5. The modified DNA duplex remains
      in a right-handed helix, which bends at the site of intercalation about 20 to 30
      degrees away from the helical axis and toward the direction of the modified
      strand.

PMID- 7577947
TI  - Interaction of the UvrABC nuclease system with a DNA duplex containing a single
      stereoisomer of dG-(+)- or dG-(-)-anti-BPDE.
AB  - Oligonucleotides containing site-specifically-modified N2-guanine (+)-trans-, (-)
      trans-, (+)-cis-, and (-)-cis-BPDE adducts were ligated into 50-base-pair DNA
      fragments. These substrates were used in reactions with the Escherichia coli
      UvrABC nuclease system. The interaction of the UvrA2 and UvrA2B complexes with
      these four stereoisomers was probed using DNase I footprinting and gel mobility
      shift assays. DNase I digestion of substrates containing each stereoisomer of
      BPDE displayed a unique pattern which was consistent with the known structure of
      these DNA adducts. UvrA and UvrA2B appeared to interact very similarly with all
      four substrates. Binding of UvrA2 to these substrates produced a 33-bp footprint,
      and the UvrB--DNA complex resulted in footprint of 24 bp. The UvrABC nuclease
      system produced bimodal incisions at the eighth phosphate 5' and the fifth,
      sixth, or seventh phosphate 3' to the modified guanine. The variation of the 3'
      incision site was linked to the stereochemistry and orientation of the BPDE
      adduct. For example, the 3' incision of the 50-bp duplex containing (-)-trans
      BPDE-N2-guanine was inhibited at the fifth phosphate. UvrABC nuclease incision
      kinetics revealed a hierarchy of specificity. The intercalative cis isomers were
      incised more efficiently than the corresponding trans isomers which lie in the
      minor groove. The (+) enantiomers were incised more efficiently than the (-) form
      for both cis and trans isomers. These observations reveal that UvrABC nuclease
      recognition and incision are directly influenced by the conformation of the DNA
      adduct.

PMID- 7577948
TI  - Kinetic analysis of cyclophilin-catalyzed prolyl cis/trans isomerization by
      dynamic NMR spectroscopy.
AB  - To investigate the kinetics of the prolyl peptide bond cis/trans isomerization of
      N-succinyl-Ala-Phe-Pro-Phe-(4)-nitroanilide catalyzed by peptidyl prolyl
      cis/trans isomerases (PPIases), one-dimensional dynamic 1H NMR spectroscopy was
      employed. To this end line shape analyses of proton signals were performed at
      various concentrations of both cytosolic porcine kidney cyclophilin (Cyp18) and
      peptide substrate. Catalysis of the cis/trans isomerization by Cyp18 is best
      described by a four-site exchange model, where the four sites represent the cis
      and trans isomers free in solution and bound to the enzyme. Combination of
      dynamic NMR spectroscopy with the classical protease-coupled PPIase assay allowed
      determination of the complete set of the microscopic rate constants describing
      the four site exchange model. The comparison of the rate constants of cis-->trans
      isomerization of the peptide free in solution and bound to cyclophilin yields an
      acceleration factor of 3.5 x 10(5). Dissociation of the Michaelis complexes are
      of the same order of magnitude as the isomerization rates on the enzyme.
      Therefore, all microscopic rate constants contribute to the steady state
      parameters. For the first time, the kcat (620 s-1) and KM (220 microM) value for
      the trans isomer in addition to the values of the cis isomer (kcat = 680 s-1, KM
      = 80 microM) could be determined under reversible conditions at pH 6.0 and 10
      degrees C. The affinity of Cyp18 for the cis isomer is 4 times higher than for
      the trans isomer. This results in a shift of the cis/trans equilibrium toward the
      cis isomer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577950
TI  - The structural basis for pseudoreversion of the E165D lesion by the secondary
      S96P mutation in triosephosphate isomerase depends on the positions of active
      site water molecules.
AB  - The structural basis for the improvement in catalytic efficiency of the mutant
      E165D chicken triosephosphate isomerase by the secondary mutation, S96P, has been
      analyzed using a combination of X-ray crystallography and Fourier transform
      infrared spectroscopy. All X-ray structures were of the complex of
      phosphoglycolohydroxamate (PGH), an intermediate analog, with the isomerase, and
      each was solved to a resolution of 1.9 A. Comparison of the structure of the
      double mutant, E165D.S96P, with that of the single mutant, E165D, as well as with
      the wild-type isomerase shows only insignificant differences in the positions of
      the side chains in all of the mutants when compared with the wild-type isomerase,
      except that in both the E165D and E165D.S96P mutants, the aspartate side chain
      was approximately 0.7 A further away from the substrate analog than the glutamate
      side chain. Significant differences were observed in the crystal structure of the
      E165D.S96P double mutant in the positions of ordered water molecules bound at the
      active site. The loss of two water molecules located near the side chain at
      position 165 was observed in isomerases containing the S96P mutation. The
      resulting increase in hydrophobicity of the pocket probably causes an increase in
      the pKa of the catalytic base, D165, thereby improving its basicity. A new
      ordered water molecule was observed underneath the bound PGH in the E165D.S96P
      structure, which likely decreases the pKa's of the substrate protons, thereby
      increasing their acidity. An enzyme derived carbonyl stretch at 1746 cm-1 that is
      only observed in the IR spectrum of the E165D.S96P double mutant isomerase with
      bound substrates has been assigned to a stable ground state protonated D165
      enediol(ate) intermediate complex. Thus, the gain in activity resulting from the
      S96P second site change probably results from a combination of improving the
      basicity of the enzyme, improving the acidity of the substrate protons, and
      stabilization of a reaction intermediate. All three of these effects seem to be
      caused by changes in bound water molecules.

PMID- 7577949
TI  - Characterization of the arachidonate and ATP binding sites of human 5
      lipoxygenase using photoaffinity labeling and enzyme immobilization.
AB  - The arachidonic acid and the ATP binding sites of human 5-lipoxygenase were
      characterized using photoaffinity labeling and immobilization of the enzyme on
      ATP-agarose. Photoaffinity labeling of the active site of 5-lipoxygenase was
      achieved with a novel thiopyranoindole inhibitor containing a 4-azido-3
      iodobenzenesulfonyl moiety (L-708,714). This probe was found to inhibit the
      activity of 5-lipoxygenase (IC50 = 0.3 microM) and to covalently label the enzyme
      after UV light irradiation. The labeling was inhibited by arachidonic acid, N
      hydroxyurea, and dihydrobenzofuranol inhibitors which have been shown to reduce
      the non-heme iron center of 5-lipoxygenase. Photoaffinity labeling of 5
      lipoxygenase by L-708,714 was dependent on the presence of both Ca2+ ions and
      phospholipids and was independent of ATP. It occurred at similar levels using
      native (Fe2+), oxidized (Fe3+), or H2O2-inactivated enzyme, but was abolished by
      heat inactivation of the enzyme. Competition of the labeling by various
      thiopyranoindoles and other inhibitors such as L-697,198,ZD-2138, and zileuton
      was found to be related to their inhibitory potency. Immobilized 5-lipoxygenase
      on ATP-agarose was found to be selectively eluted by adenine nucleotides (ATP >
      ADP > AMP) but not by solutions containing high salt concentrations, mild
      detergents, arachidonic acid, or inhibitors. 5-Lipoxygenase inhibitors were
      selectively retained on the immobilized enzyme and eluted by buffer containing
      arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577951
TI  - Interaction of substrate and effector binding sites in the ArsA ATPase.
AB  - The ars operon of plasmid R773 confers resistance to antimonials and arsenicals
      in Escherichia coli by encoding an ATP-dependent extrusion system for the
      oxyanions. The catalytic subunit, the ArsA protein, is an ATPase with two
      nucleotide binding consensus sequences, one in the N-terminal half and one in the
      C-terminal half of the protein. The ArsA ATPase is allosterically activated by
      tricoordinate binding of As(3+) or Sb(3+) to three cysteine thiolates. Previous
      measurements suggested that the intrinsic fluorescence of tryptophans might be
      useful for examining binding of Mg2+ ATP and antimonite. In the present study an
      increase in intrinsic tryptophan fluorescence was observed upon addition of Mg2+
      ATP. This enhancement was reversed by addition of antimonite. The ArsA protein
      contains four tryptophan residues: Trp159, Trp253, Trp522, and Trp524. The first
      two were altered to tyrosine residues by site-directed mutagenesis. Cells
      expressing both the arsAW159Y and arsAW253Y mutations retained resistance to
      arsenite, and the purified W159Y and W253Y proteins retained ATPase activity.
      While the intrinsic tryptophan fluorescence of the W253Y protein responded to
      addition of Mg2+ ATP, intrinsic tryptophan fluorescence in the purified W159Y
      protein was no longer enhanced by substrate. These results suggest that Trp159 is
      conformationally coupled to one or both of the nucleotide binding sites and
      provides a useful probe for the interaction of effector and substrate binding
      sites.

PMID- 7577952
TI  - [125I]margatoxin, an extraordinarily high affinity ligand for voltage-gated
      potassium channels in mammalian brain.
AB  - Monoiodotyrosine margatoxin ([125I]MgTX) specifically and reversibly labels a
      maximum of 0.8 pmol of sites/mg of protein in purified rat brain synaptic plasma
      membrane vesicles with a dissociation constant of 0.1 pM under equilibrium
      binding conditions. This Kd value was confirmed by kinetic experiments (Kd of
      0.07 pM), competition assays employing native margatoxin (MgTX) (Ki of 0.15 pM),
      and receptor saturation studies (Kd of 0.18 pM). Thus, this toxin represents the
      highest affinity, reversible radioligand for any membrane-bound receptor or ion
      channel described to date. [125I]MgTX binding in this system is modulated by
      charybdotoxin (Ki of 5 pM), kaliotoxin (Ki of 1.5 pM), and the agitoxins I and II
      (Ki's of 0.1 and 0.3 pM, respectively), in a noncompetitive manner. Moreover,
      alpha-dendrotoxin displayed a Ki value of 0.5 pM. Iberiotoxin was without any
      effect, suggesting that the receptor site is likely to be associated with a
      voltage-gated K+ channel complex. [125I]MgTX binding is inhibited by cations that
      are established blockers of voltage-dependent K+ channels (Ba2+, Ca2+, Cs+). The
      monovalent cations Na+ and K+ stimulate binding at low concentrations before
      producing complete inhibition as their concentrations are increased. Stimulation
      of binding results from an allosteric interaction that decreases Kd, whereas
      inhibition is due to an ionic strength effect. Affinity labeling of the binding
      site in rat brain synaptic plasma membranes employing [125I]MgTX and the
      bifunctional cross-linking reagent, disuccinimidyl suberate, causes specific and
      covalent incorporation of toxin into a glycoprotein of an apparent molecular
      weight (M(r)) of 74,000. Deglycosylation studies reveal an M(r) for the core
      polypeptide of the MgTX receptor of 63,000.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577953
TI  - pH dependence of ligand binding to D2 dopamine receptors.
AB  - The binding of a range of ligands to D2 dopamine receptors in bovine caudate
      nucleus and recombinant CHO cells expressing the receptor has been determined at
      different pH values between 4.5 and 8.5. The maximum number of D2 dopamine
      receptor binding sites in each tissue was not affected by the change in pH, but
      the affinity of ligands for binding to the receptors was decreased as the pH was
      decreased. For classical dopamine antagonists, e.g. spiperone and haloperidol,
      the data on pH dependence of the dissociation constant for receptor binding
      indicated that the protonation of a single ionizing group on the receptor (pKa
      approximately 6) influenced the binding process. For antagonists of the
      substituted benzamide class, the data indicated that the protonation of two
      ionizing groups (pKa between 6 and 7) influenced the ligand binding process.
      These ionizing residues may correspond to Asp 114 for the classical antagonists
      and Asp 114 and Asp 80 for the substituted benzamide antagonists. Further
      evidence for the participation of carboxyl residues in the ligand binding process
      was obtained from the inhibition by N,N'-dicyclohexylcarbodiimide of the binding
      of [3H]spiperone and [3H]YM 09151-2 to D2 receptors in the recombinant CHO cells.

PMID- 7577954
TI  - Oxidation of kinetically trapped thiols by protein disulfide isomerase.
AB  - The formation of a stabilized structure during oxidative protein folding can
      severely retard disulfide formation if the structure must be disrupted to gain
      access to buried cysteines. These kinetic traps can slow protein folding and
      disulfide bond formation to the extent that unassisted folding is too slow to be
      kinetically competent in the cell. Protein disulfide isomerase (PDI) facilitates
      the oxidation of a kinetically trapped state of RTEM-1 beta-lactamase in which
      two cysteines that form the single disulfide bond in the native protein are
      buried and approximately 500-fold less reactive than exposed cysteines. Under
      second-order conditions, PDI-dependent oxidation of reduced, folded beta
      lactamase is 500-fold faster than GSSG-dependent oxidation. The rate difference
      observed between PDI and GSSG can be accounted for by the 520-fold higher kinetic
      reactivity of PDI as an oxidant. Noncovalent interactions between PDI (35 microM)
      and beta-lactamase increase the reactivity or unfolding of beta-lactamase in the
      steady-state by less than 3-fold. At high concentrations of PDI or alkylating
      agents, the reaction of beta-lactamase cysteines approaches a constant rate,
      limited by the spontaneous unfolding of the protein (kunfold = 0.024 +/- 0.005
      min-1). PDI does not substantially increase the rate of beta-lactamase unfolding;
      however, once beta-lactamase spontaneously unfolds, PDI at concentrations greater
      than 44 +/- 4 microM, oxidizes the unfolded substrate before it can refold (kfold
      = 1.5 +/- 0.2 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577955
TI  - Ribonuclease A revisited: infrared spectroscopic evidence for lack of native-like
      secondary structures in the thermally denatured state.
AB  - To address a number of conflicting reports in the literature, we undertook an
      infrared spectroscopic study to test for the presence of native-like secondary
      structures in thermally denatured ribonuclease A. Ribonuclease A does not
      aggregate at high temperatures, and the infrared spectrum shows a completely
      featureless amide I band contour. Using 13C-labeled urea, we were also able to
      obtain the infrared spectrum of the chemically denatured protein, which is
      practically identical with that of the heat-denatured protein. To the best of our
      knowledge, this is the first study that uses 13C-labeled urea as a chemical
      denaturant which circumvents the problem encountered with the strong absorption
      of urea in the conformation-sensitive amide I region of proteins; it opens up the
      possibility of investigating protein folding/unfolding processes in the presence
      of high concentrations of chemical denaturants. From an analysis of the amide I
      region of the infrared spectra of thermally and chemically denatured RNase A, it
      was concluded that heat-denatured ribonuclease A does not contain any significant
      amount of authentic hydrogen-bonded secondary structures. Furthermore, a
      comparison of the infrared spectra of ribonuclease A with those of ribonuclease
      T1 demonstrates that in spite of major differences between their native
      structures there are practically no differences between their heat-denatured
      states. This would not be expected if there were residual native-like secondary
      structures in the thermally denatured state of one or both of these proteins.

PMID- 7577956
TI  - Movement of the position of the transition state in protein folding.
AB  - Hammond behavior, in which two neighboring states move closer to each other along
      the reaction coordinate as the energy difference between them becomes smaller,
      has previously been observed for the transition state of unfolding of barnase.
      Here, we report Hammond behavior for the small protein chymotrypsin inhibitor 2
      (CI2), which folds and unfolds via a single rate-determining transition state and
      simple two-state kinetics. Mutants have been generated along the entire sequence
      of the protein and the kinetics of folding and unfolding measured as a function
      of concentration of denaturant. The transition state was found to move
      progressively closer to the folded state on destabilization of the protein by
      mutation. Different regions of CI2 all show a similar sensitivity to changes in
      the energy of the transition state. This is in contrast to the behavior of
      barnase on mutation for which the position of the transition state for its
      unfolding is sensitive to mutation in some regions, especially in its major alpha
      helix, but not in others. The transition state for the folding and unfolding of
      CI2 resembles an expanded version of the folded state and is formed in a
      concerted manner, in contrast to that for barnase, in which some regions of
      structure are fully formed and others fully unfolded. The reason for the general
      sensitivity of the position of the transition state of CI2 to mutation is
      presumably the relatively uniform degree of structure formation in the transition
      state and the concerted nature of its formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577957
TI  - Solution structure of bovine neutrophil beta-defensin-12: the peptide fold of the
      beta-defensins is identical to that of the classical defensins.
AB  - The solution structure is reported for bovine neutrophil beta-defensin-12 (BNBD
      12), a member of the beta-defensin family of antimicrobial peptides. Structural
      constraints in the form of proton-proton distances, dihedral angles, and hydrogen
      bond constraints were derived from two-dimensional, homonuclear magnetic
      resonance spectroscopy experiments. The three-dimensional structure of BNBD-12
      was calculated using distance geometry and restrained molecular dynamics. An
      ensemble of structures with low NOE constraint violation energies revealed a
      precisely defined triple-stranded, antiparallel beta-sheet as the structural core
      of the peptide. The N-terminal beta-strand and three locally well-defined tight
      turns form a hydrophobic face. Conserved isoleucine and glycine residues form a
      beta-bulge structure which initiates a beta-hairpin secondary structure motif
      composed of the second and C-terminal beta-strands. The beta-hairpin contains
      numerous charged residues and forms the cationic face of BNBD-12. The N-terminal
      residues were found to be disordered, due to an absence of tertiary NOEs. The
      triple-stranded beta-sheet, the beta-bulge preceding the hairpin, and the
      cationic/hydrophobic amphiphilic character are definitive features of all
      defensin structures determined to date. Further, we predict that the tracheal
      antimicrobial peptide (TAP) and the recently described gallinacins will have
      tertiary structures similar to that of BNBD-12.

PMID- 7577958
TI  - Transferred nuclear Overhauser enhancement experiments show that the monoclonal
      antibody strep 9 selects a local minimum conformation of a Streptococcus group A
      trisaccharide-hapten.
AB  - Transferred nuclear Overhauser enhancement (TRNOE) experiments have been
      performed to investigate the bound conformation of the trisaccharide repeating
      unit of the Streptococcus Group A cell-wall polysaccharide. Thus, the
      conformations of propyl 3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-O
      (alpha-L-rhamnopyran osyl)- alpha-L-rhamnopyranoside [C(A')B] (1) as a free
      ligand and when complexed to the monoclonal antibody Strep 9 were examined.
      Improved insights about the conformational preferences of the glycosidic linkages
      of the trisaccharide ligand showed that the free ligand populates various
      conformations in aqueous solution, thus displaying relatively flexible behavior.
      The NOE HNAc-H2A', which was not detected in previous work, accounts for a
      conformation at the beta-(1-->3) linkage with a phi angle of approximately 180
      degrees. Observed TRNOEs for the complex are weak, and their analysis was further
      complicated by spin diffusion. With the use of transferred rotating-frame
      Overhauser enhancement (TRROE) experiments, the amount of spin diffusion was
      assessed experimentally, proving that all of the observed long-range TRNOEs arose
      through spin diffusion. Four interglycosidic distances, derived from the
      remaining TRNOEs and TRROEs, together with repulsive constraints, derived from
      the absence of TRROE effects, were used as input parameters in simulated
      annealing and molecular mechanics calculations to determine the bound
      conformation of the trisaccharide. Complexation by the antibody results in the
      selection of one defined conformation of the carbohydrate hapten. This bound
      conformation, which is a local energy minimum on the energy maps calculated for
      the trisaccharide ligand, shows only a change from a +gauche to a -gauche
      orientation at the psi angle of the alpha-(1-->2) linkage when compared to the
      global minimum conformation. The results infer that the bound conformation of the
      Streptococcus Group A cell-wall polysaccharide is different from its previously
      proposed solution structure (Kreis et al., 1995).

PMID- 7577959
TI  - Interactions of acridine antitumor agents with DNA: binding energies and groove
      preferences.
AB  - Absorbance spectroscopy is used to examine the thermodynamic properties
      associated with the interaction of the experimental antitumor agents N-[2
      (dimethylamino)ethyl]-9-aminoacridine-4-carboxamide (AAC) and N-[2
      (dimethylamino)ethyl]acridine-4-carboxamide (DACA) with nucleic acids. Placement
      of the amino substituent at the C9 position on the acridine ring results in
      marked changes to the acridine chromophore's electronic properties, with the
      overall charge of AAC increasing to +2 in comparison to DACA's charge of +1 at
      neutral pH. In comparative DNA binding studies, we examine the influence that the
      electrostatic properties of these ligands have on the binding energies as well as
      their effects on enthalpy and entropy contributions. These studies show that
      placement of the amino moiety at C9 results in 6 times greater DNA binding
      affinity as compared the deamino analog (DACA). Comparisons of ionic strength
      dependence for these two analogs reveal a difference in the binding energies of
      the compounds which can be attributed to electrostatic effects. Further
      dissection of the enthalpy and entropy components of the binding energy reveals
      the enhanced electrostatic effects are related to an increased entropy
      contribution upon formation of the AAC-DNA complex. Groove selectivity of these
      acridine analogs was probed by examining the binding profiles to native and
      groove-modified DNAs which included glycosylated T4 DNA and the distamycin-DNA
      complex. These studies are indicative of minor groove interactions for both
      compounds with DNA.

PMID- 7577960
TI  - Structure and stability of protein H and the M1 protein from Streptococcus
      pyogenes. Implications for other surface proteins of gram-positive bacteria.
AB  - M proteins and other members of the M protein family, expressed on the surface of
      Streptococcus pyogenes, bind host proteins such as immunoglobulins, albumin, and
      fibrinogen. Protein H and the M1 protein are expressed by adjacent genes and both
      belong to the M protein family. In this work, the structure and stability of
      these two proteins have been investigated. As judged from sequence analysis and
      circular dichroism spectroscopy, the proteins are almost entirely in an alpha
      helix conformation. The amino acids are arranged in a seven-residue (heptad)
      repeat pattern along the greater part of the proteins. These observations support
      the previously accepted model of M proteins as coiled-coil dimers. However, it
      was also found that the structures of both proteins were thermally unstable;
      i.e., the content of helix conformation was greatly reduced at 37 degrees C as
      compared to 25 degrees C or below. Together with previous findings that these
      proteins appear as monomers at 37 degrees C and dimers at low temperatures, the
      results suggest that the coiled-coil dimers are unfolded at 37 degrees C. The
      heptad patterns of protein H and the M1 protein showed a nonoptimal distribution
      of residues expected for a coiled-coil conformation. This is a possible
      explanation for the low thermal stability of the proteins. It was also
      demonstrated that the proteins were stabilized in the presence of the ligands IgG
      and/or albumin. Protein H and M1 protein show a high degree of sequence
      similarity in their C-terminal regions, and a fragment from this region displayed
      a high content of helix conformation, whereas fragments from the nonsimilar N
      terminal parts did not adopt any stable folded structure. Thus, the C-terminal
      parts, which are conserved within the M protein family, may constitute a
      framework for the formation of the parallel helical coiled-coil structure, and we
      propose that the less stable N-terminal part may also participate in antiparallel
      interaction with M proteins on adjacent bacteria. The results suggest that
      temperature fluctuations in the environment could change the properties of
      bacterial surface proteins, thereby affecting the molecular interactions between
      the bacterium and its host.

PMID- 7577961
TI  - Inhibition of prothrombinase at macroscopic lipid membranes: competition between
      antithrombin and prothrombin.
AB  - The kinetics of inhibition of prothrombinase during prothrombin conversion by
      antithrombin and antithrombin-heparin complexes was studied in a tubular flow
      reactor. Prothrombinase was assembled at a macroscopic phospholipid membrane,
      composed of 25 mol % phosphatidylserine and 75 mol % phosphatidylcholine,
      deposited on the inner wall of a glass capillary, by perfusion with a factor Xa
      factor Va mixture. Measurement of thrombin production allowed estimation of the
      amount of prothrombinase present at the capillary wall. Perfusion with a mixture
      of prothrombin and antithrombin or antithrombin-heparin complexes caused a
      progressive decline of the prothrombinase activity. The rate of inactivation
      steeply decreased with increasing prothrombin concentrations, indicating
      competitive inhibition. Analysis of competitive inhibition data requires
      estimation of the time-dependent substrate concentration, Co, near the
      prothrombin converting surface using earlier developed transport theory [Billy,
      D., et al. (1995) J. Biol. Chem. 270, 1029-1034]. It appears that the inhibition
      rate is proportional to the fraction of enzyme, Km/(Km+Co), not occupied by
      substrate. The value of Km of prothrombinase estimated from the dependence of the
      inhibition rate on the prothrombin concentration (Km = 2-3 nM) is in excellent
      agreement with the value estimated from the substrate conversion rate (Km = 3
      nM). Therefore inhibition of prothrombinase by antithrombin and antithrombin
      heparin complexes is fully competitive with the substrate: prothrombin. Our
      results show that prothrombinase assembled on macroscopic lipid surfaces by
      virtue of its low Km value is protected for inhibition due to highly effective
      competition of prothrombin with antithrombin for the active site of factor Xa.

PMID- 7577962
TI  - Aggregation of acidic lipid vesicles by myelin basic protein: dependence on
      potassium concentration.
AB  - In the compacted multilayered myelin sheath of the central nervous system, myelin
      basic protein (MBP) is thought to be responsible for adhesion of the
      intracellular surfaces by electrostatic interactions with acidic lipids.
      Noncompacted regions of myelin containing cytosol exist and can take up potassium
      released into the extracellular fluid after the axonal action potential.
      Therefore, the effect of K+ concentration on the ability of MBP to aggregate
      large unilamellar vesicles (LUVs) containing phosphatidylcholine (PC) and 10-20%
      acidic lipid was investigated. At MBP to lipid ratios where there was an excess
      of acidic lipid, physiological increases in K+ concentration up to about 100 mM
      greatly increased MBP-mediated aggregation of the LUVs by shielding the negative
      charge on the vesicle surface. Thus, changes in K+ concentration during the
      axonal action potential could regulate MBP-mediated adhesion of the intracellular
      myelin surfaces of noncompacted regions of myelin such as the paranodal loops. It
      could thus regulate the volume of these cytosolic regions, allowing MBP to have a
      dynamic function in myelin. Concentrations of K+ above 150 mM caused dissociation
      of MBP from LUVs containing PC and a single acidic lipid. LUVs containing the
      lipid composition estimated to be characteristic of the cytoplasmic leaflet of
      myelin (Cyt.-LUVs) were found to interact uniquely with MBP, resulting in greater
      aggregation, greater sensitivity to K+ concentration, and resistance to
      dissociation at high K+ concentrations. The latter suggested that electrostatic
      interactions were not the only force involved in binding of MBP to the Cyt.-LUVs.
      Hydrogen bonding of the protein to the lipid head groups and hydrophobic
      interactions due to penetration of hydrophobic amino acid side chains into the
      bilayer could also occur. The greater involvement of hydrophobic interactions of
      MBP with Cyt.-LUVs compared to PC/acidic lipid LUVs was confirmed from greater
      labeling of MBP bound to Cyt.-LUVs by the hydrophobic photolabeled TID.
      Cholesterol and phosphatidylethanolamine together were found to be responsible
      for the greater MBP-mediated aggregation of Cyt.-LUVs and the greater TID
      labeling of MBP bound to Cyt.-LUVs compared to PC/acidic lipid LUVs. Thus, the
      lipid composition of the intracellular surface of myelin is well suited to allow
      MBP to mediate adhesion of apposing intracellular membranes and to respond in a
      dynamic way in some regions of myelin, such as the paranodal loops, to changes in
      K+ concentration resulting from nerve conduction.

PMID- 7577963
TI  - Role of ligand in retinoid signaling. 9-cis-retinoic acid modulates the
      oligomeric state of the retinoid X receptor.
AB  - Many of the effects of retinoids on cells are mediated by the transcription
      factors known as retinoid nuclear receptors, but the mechanisms by which
      retinoids regulate the activity of the receptors are not known. It was previously
      shown that the retinoid X receptor (RXR) forms tetramers with a high affinity. In
      the present work it is demonstrated that binding of 9-cis-retinoic acid to RXR
      leads to rapid dissociation of receptor tetramers. In addition, fluorescence
      anisotropy studies indicate that ligand-binding results in a significant
      conformational change such that holo-RXR is more compactly folded as compared to
      the apo-protein. These findings suggest that the initial event in signaling by 9
      cis-retinoic acid is a change in the oligomeric state of RXR. The data also imply
      that tetramer formation is a regulatory feature of the pathway by which RXR
      mediates the effects of retinoids on gene transcription.

PMID- 7577964
TI  - Reduced albumin binding promotes the stability and activity of topotecan in human
      blood.
AB  - Topotecan, a semisynthetic water-soluble analogue of camptothecin, is the first
      topoisomerase I targeting anticancer agent to enter comparative phase III
      clinical trials. Here we elucidate the biophysical factors underlying the
      markedly improved bloodstream stability and cytotoxic activity of topotecan
      relative to camptothecin. Each agent contains an alpha-hydroxy-delta-lactone ring
      that hydrolyzes under physiological pH to yield a biologically-inactive
      carboxylate form. In human plasma, camptothecin lactone converts rapidly and
      completely to its carboxylate form due to a 200-fold binding preference by serum
      albumin (HSA) for the latter [Mi, Z., & Burke, T.G. (1994) Biochemistry 33, 10540
      12545]. Time-resolved fluorescence anisotropy measurements reveal that neither
      topotecan lactone nor carboxylate associates with HSA, thereby resulting in a
      significantly higher level of lactone stability in plasma for topotecan (t1/2 =
      23.1 min, percent lactone at equilibrium of 17.6) relative to camptothecin (t1/2
      = 10.6 min, percent lactone at equilibrium of < 0.2). Moreover, studies with HL
      60 human promyelocytic leukemia cells reveal that a physiologically-relevant
      level (40 mg/mL) of HSA dramatically attenuates the cytotoxic activity of
      camptothecin in excess of 2600-fold (for a 72 h exposure, the IC50 value of 1.5
      nM in the absence of HSA increased to 4 microM in the presence of HSA). The
      activities of other clinically relevant anticancer analogues, 9-aminocamptothecin
      and SN-38, were also strongly modulated by the presence of 40 mg/mL HSA. In
      marked contrast, the presence of HSA effected no change on the cytotoxic activity
      of topotecan (IC50 = 12 nM both in the absence and in presence of HSA).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577965
TI  - Localization of a transcription promoter within the second exon of the cytochrome
      P-450c27/25 gene for the expression of the major species of two-kilobase mRNA.
AB  - The rat P-450c27/25 (CYP27) gene is expressed as two distinctly sized mRNAs of 2
      and 2.3 kb (kilobase). The 2 kb mRNA is the predominant form in the liver with
      negligible 2.3 kb species. Rat kidney and hepatoma, on the other hand, contain
      significant levels of the 2.3 kb species. Rat CYP27 gene contains 11 exons of 80
      415 nucleotides that are separated by 10 introns of 83 bases to approximately 10
      kb. S1 nuclease protection and primer extension analyses using liver RNA showed a
      prominent 5' terminus 86 nucleotides downstream from the start of exon 2. This
      site, designated as +1, is the start site for the 2 kb mRNA. 5' RACE analysis of
      rat kidney and hepatoma RNAs showed the presence of a 5' extended mRNA with a
      sequence complementary to the Spi2 mRNA. A cryptic TATA box (TTTAAA) is located
      24 nucleotides upstream of the 2 kb mRNA transcription initiation site at +1. A
      106 bp DNA fragment (sequence -83 to +23) that houses the putative TATA motif
      forms three differently migrating complexes with nuclear extract from the murine
      3T3 cells. DNAse I footprinting and competition with synthetic DNA showed that
      complex A represents the bound Sp1 factor and complexes B and C are due to
      unknown factors binding to the -83 to -71 and -20 to -12 sequences, respectively.
      In vivo transcription analysis using -840/+23 DNA and its 5' deletions cloned in
      a CAT reporter plasmid suggests that the basal promoter elements are located
      within sequence -45 to +23 of the gene. Finally, in vitro transcription analysis
      in HeLa cell nuclear extract showed that intact TTTAAA motif and complex C
      forming sequence from this region are essential for transcription initiation at
      the +1 position of the promoter. Our results demonstrate that the 2 kb mRNA is
      transcribed as an independent transcript driven by an immediate upstream promoter
      located within exon 2.

PMID- 7577966
TI  - Protein-protein interactions in colicin E9 DNase-immunity protein complexes. 1.
      Diffusion-controlled association and femtomolar binding for the cognate complex.
AB  - The cytotoxic activity of the secreted bacterial toxin colicin E9 is due to a
      nonspecific DNase housed in the C-terminus of the protein. A kinetic and
      thermodynamic analysis of complex formation for both the holotoxin and the
      isolated DNase domain with the cytoplasmic inhibitor of this enzyme, the immunity
      protein Im9, is presented. The dissociation constant for each complex was
      calculated from the ratio of the association and dissociation rate constants.
      Association was monitored by stopped-flow fluorescence and comprises at least two
      steps for both complexes, an initial fluorescence enhancement followed by a
      fluorescence quench. The data are consistent with a two-step binding mechanism in
      which the rate of formation of an encounter complex (k1) is rate determining and
      essentially diffusion controlled (4.0 x 10(9) M-1 s-1 for colicin E9) in buffer
      of low ionic strength. This encounter complex then rearranges to the final stable
      complex. Sequential stopped-flow experiments using 5-hydroxy-L-tryptophan labeled
      DNase domain support the two-step mechanism and further show that the rate of
      encounter complex rearrangement is significantly faster than its dissociation.
      The overall rate of dissociation of the colicin E9-Im9 complex (k(off)) was
      determined by radioactive subunit exchange to be 3.7 x 10(-7) s-1. Thus, the Kd
      for the complex (k(off)/k1) is 9.3 x 10(-17) M, which corresponds to a change in
      free energy on binding of -21.9 kcal mol-1 at 25 degrees C.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7577967
TI  - Protein-protein interactions in colicin E9 DNase-immunity protein complexes. 2.
      Cognate and noncognate interactions that span the millimolar to femtomolar
      affinity range.
AB  - The in vivo and in vitro cross-binding of the colicin endonuclease-specific
      immunity proteins toward the DNase domain of colicin E9 is described. In vivo
      cross-protection was tested by toxin plate assays in which bacterial cells
      overexpressing each immunity (Im2, Im7, Im8, and Im9) were challenged with the
      ColE9 toxin. Im9, the cognate immunity protein, renders cells completely
      resistant toward very high concentrations of the toxin (> 1 mg/mL), whereas the
      noncognate immunities display a spectrum of weaker cross-reactivities (< 0.01
      mg/mL). The order of biological protection in this assay was Im9 >> Im2 > Im8,
      with Im7 providing no colicin E9 resistance. In vitro binding between the
      immunity proteins and the E9 DNase was analyzed by determining the dissociation
      constants for E9 DNase-Im protein complexes at pH 7.0 in the presence of 200 mM
      salt and at 25 degrees C. Stopped-flow fluorescence experiments suggest that both
      Im2 and Im8 associate with the E9 DNase by a two-step mechanism, in which the
      rate constants for both the bimolecular association (k1 = approximately 6 x 10(7)
      M-1 s-1) and the subsequent conformational change (k2 + k-2 = 4-5 s-1) are very
      similar to Im9 binding under the same conditions. Fluorescence chase experiments
      defined the dissociation rate constants for Im2 and Im8. The estimated values are
      10(6)- and 10(8)-fold, respectively, faster than the off-rate for the Im9
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577968
TI  - Melanoma growth stimulatory activity signaling through the class II interleukin-8
      receptor enhances the tyrosine phosphorylation of Crk-associated substrate, p130,
      and a 70-kilodalton protein.
AB  - Binding of the CXC chemokine, melanoma growth stimulatory activity (MGSA), to the
      class II IL-8 receptor on cells which overexpress this G-protein coupled receptor
      results in enhanced phosphorylation on serine residues. In experiments described
      herein, it is demonstrated that MGSA also enhances the tyrosine phosphorylation
      of two endogenously tyrosine phosphorylated proteins approximately 130 and 70 kDa
      in size. MGSA treatment (5 nM) of the clonally selected, stably transfected
      placental cell line, 3ASubE P-3, which overexpresses the class II IL-8 receptor,
      results in the maximal tyrosine phosphorylation of the 130 kDa protein before 2
      min. This enhanced phosphorylation of the 130 kDa protein returns to basal level
      after a 5 min treatment. Based upon cell fractionation studies, the 130 kDa
      protein is concentrated in the membrane fraction of the cells. The 70 kDa protein
      which also shows tyrosine phosphorylation is predominantly cytosolic. The
      identity of the 130 kDa tyrosine phosphorylated protein was determined by
      immunoprecipitation and Western blot analyses. In these experiments, the 130 kDa
      tyrosine phosphorylated protein was shown to immunoprecipitate with antibody to
      the cas antigen (crk-associated substrate) and with antibody to the p130 tyrosine
      phosphorylated protein described as undergoing tyrosine phosphorylation in src
      transformed cells. The data suggest that MGSA binding to the class II IL-8
      receptor is associated with tyrosine phosphorylation of p130/cas. The data also
      suggest that p130 and the cas antigen are the same protein.

PMID- 7577969
TI  - Transglutaminase-catalyzed cross-linking of fibrils of collagen V/XI in A204
      rhabdomyosarcoma cells.
AB  - Collagens V and XI are thought to form a core around which the major interstitial
      collagens, I and II, respectively, are organized during fibrillogenesis. We
      previously reported the presence of a heterotypic form of collagens V and XI,
      [alpha 1(XI)]2 alpha 2(V), in cultures of A204 rhabdomyosarcoma cells [Kleman, J.
      P., Hartmann, D. J., Ramirez, F., & van der Rest, M. (1992) Eur. J. Biochem. 210,
      329-335]. This collagen forms a matrix which remains highly insoluble, even when
      cells were cultured in the presence of beta-aminopropionitrile, an inhibitor of
      lysyl oxidase and thereby of "classical" collagen cross-linking. When the cells
      were cultured in the presence of putrescine, a competitive inhibitor of
      transglutaminase-catalyzed protein cross-linking, a drastic increase in collagen
      solubility was observed. This result indicates that a transglutaminase
      contributes to the covalent stabilization of the collagen matrix of these cells.
      A204 rhabdomyosarcoma cells express tissue transglutaminase as revealed by
      specific antibodies, and enzyme activity was detected in the cell layer during
      culture and in cell extracts. Both collagens V and XI are specific glutaminyl
      substrates for tissue transglutaminase in vitro, as shown by incorporation of
      [3H]putrescine. The highly homologous alpha 1 chains of collagens V and XI were
      the major targets for the cross-linking. Trypsin cleaved the [3H] label from the
      alpha 1 chain of collagen V, demonstrating that the cross-linking occurs in the
      non triple helical propeptide domains.

PMID- 7577970
TI  - Properties and regulation of the catalytic domain of Ira2p, a Saccharomyces
      cerevisiae GTPase-activating protein of Ras2p.
AB  - This work describes the biochemical characterization of the catalytic domain of
      Ira2p, a Saccharomyces cerevisiae GTPase-activating protein (GAP) regulating the
      RAS gene products. A fragment of 383 residues (amino acids 1644-2026) was
      produced in Escherichia coli as glutathione S-transferase fusion protein (GST
      Ira2p-383) and highly purified (> 90%) by affinity chromatography. The affinity
      of Ras2p for the GST-fused Ira2p-383 was 18 microM and the maximal stimulation of
      the Ras2p GTPase activity 6,000 times. The Ira2p activity was confirmed to be
      strictly specific for Ras2p, no stimulatory effect on human c-H-ras p21 GTPase
      being detectable. Comparison with the GAP-like domain of mammalian p120-GAP and
      neurofibromin using yeast Ras2p as substrate showed that Ira2p-383 has an
      affinity and turnover intermediary between GAP-334 and NF1-414. The activity of
      Ira2p-383 was strongly inhibited by monovalent and divalent salts. The
      simultaneous presence of the catalytic domains of Ira2p and the yeast GDP/GTP
      exchange factor Cdc25p induced on Ras2p a multiple-round reaction of GTP
      hydrolysis and GDP/GTP exchange, showing that it is possible to reconstitute in
      vitro a S. cerevisiae system suitable for the study of the regulation of the
      Ras2p GDP/GTP cycle. The tubulin partially inhibited (25%) the GAP activity of
      the Ira2p-383. A larger Ira2p catalytic fragment, Ira2p-505 (amino acids 1549
      2053), that showed the same Km for Ras2p as Ira2p-383, was also inhibited by
      tubulin to the same extent but with a higher affinity than Ira2p-383.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577971
TI  - Alteration of the myometrial plasma membrane cholesterol content with beta
      cyclodextrin modulates the binding affinity of the oxytocin receptor.
AB  - To investigate the effect of cholesterol on the oxytocin receptor function in
      myometrial membranes, we developed a new method to alter the membrane cholesterol
      content. Using a methyl-substituted beta-cyclodextrin, we were able to
      selectively deplete the myometrial plasma membrane of cholesterol. Vice versa,
      incubating cholesterol-depleted membranes with a preformed soluble cholesterol
      methyl-beta-cyclodextrin complex restored the cholesterol content of the plasma
      membrane. Binding experiments showed that, with the removal of cholesterol from
      the membrane, the dissociation constant for [3H]oxytocin is enhanced 87-fold
      (from Kd = 1.5 nM to Kd = 131 nM), therefore shifting the oxytocin receptor from
      high to low affinity. Increasing the cholesterol content of the cholesterol
      depleted membrane again restored the high-affinity binding (Kd = 1.2 nM). The
      presence of 0.1 mM GTP gamma S did not significantly change the number of high
      affinity binding sites for [3H]oxytocin in native plasma membranes, in membranes
      depleted of cholesterol, and in plasma membranes with restored cholesterol
      content. The number of high-affinity binding sites for the oxytocin antagonist
      [3H]PrOTA was dependent in the same way on the cholesterol content as for
      [3H]oxytocin. Substitution of the membrane cholesterol with other steroids showed
      a strong dependence of the oxytocin receptor function on the structure of the
      cholesterol molecule. The detergent-solubilized oxytocin receptor was not
      saturable with [3H]oxytocin even at concentrations up to 10(-6) M of radioligand.
      Addition of the cholesterol-methyl-beta-cyclodextrin complex to the detergent
      solubilized oxytocin receptor induced a saturation of the solubilized binding
      sites (Bmax = 0.98 pmol/mg) for oxytocin (Kd = 16 nM).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577972
TI  - Expression of the human oxytocin receptor in baculovirus-infected insect cells:
      high-affinity binding is induced by a cholesterol-cyclodextrin complex.
AB  - We have expressed a c-myc epitope-tagged human oxytocin receptor in the
      baculovirus/Sf9 cell system. The receptor was identified by SDS-PAGE and
      subsequent immunoblot as a approximately 50 kDa protein which decreased to about
      44 kDa upon treatment with tunicamycin. Binding studies showed that the human
      oxytocin receptor was expressed in a low-affinity state (Kd = 215 nM; Bmax = 1.66
      pmol/mg). After addition of cholesterol in the form of a soluble cholesterol
      methyl-beta-cyclodextrin complex to the membranes, we obtained part of the human
      oxytocin receptor in its high-affinity state for oxytocin (Kd = 0.96 nM and Bmax
      = 318 fmol/mg of protein). In subsequent studies, we added the cholesterol-methyl
      beta-cyclodextrin complex to the Sf9 cell culture medium at various times post
      infection. Binding analysis showed that this results in a more than 3-fold
      further increase in functional receptor binding sites of high-affinity state
      (Bmax = 1.08 pmol/mg). The cholesterol effect was dose-dependent, with an EC50 of
      about 50 microM cholesterol. Due to these findings, we determined the cholesterol
      and phospholipid content in purified Sf9 plasma membranes. The untreated
      naturally cholesterol auxotroph insect cells grown in medium with 2% fetal calf
      serum had a molar cholesterol/phospholipid ratio of about 0.04, which is
      approximately 20-fold lower than normally found in plasma membranes of higher
      eukaryotic cells. The high-affinity binding of the oxytocin receptor increased in
      parallel with the cholesterol levels present in the corresponding plasma
      membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577973
TI  - The interaction of cytochrome oxidase with hydrogen peroxide: the relationship of
      compounds P and F.
AB  - Upon reaction of cytochrome oxidase with hydrogen peroxide, the spectral changes
      are complete, with slightly less than 1 equiv of hydrogen peroxide per cytochrome
      oxidase. At pH 8 the product is a mixture of the P and F forms, while at pH 6 the
      product is exclusively the F form. These data are inconsistent with current
      interpretations of the structure of compounds P and F. Two stable radical species
      are detected by EPR; the relative amounts of these species are pH dependent. The
      MCD spectra of pure P and F are reported. It is suggested that compound F is a
      hydrogen peroxide adduct of cytochrome oxidase with cytochrome a3 in the low-spin
      state and that compound P is an oxyferryl state of cytochrome alpha 3 in support
      of the recent Raman data of Proshlyakov et al. [(1994) J. Biol. Chem. 269, 29385
      29388]. We also suggest that copper B is in the trivalent state in compound P.

PMID- 7577974
TI  - Quantitation of the phase preferences of the major lipids of the Acholeplasma
      laidlawii B membrane.
AB  - We have quantitated the phase preferences of all of the quantitatively
      significant lipids of fatty acid-homogeneous Acholeplasma laidlawii membranes by
      determining the effect of small amounts of each lipid on the lamellar/reversed
      hexagonal phase transition temperature of a phosphatidylethanolamine matrix of
      identical fatty acid composition using differential scanning calorimetry. We find
      that the incorporation of small amounts of these lipids produce effects ranging
      from a moderate depression to a marked elevation of the lamellar/reversed
      hexagonal phase transition temperature of the corresponding
      phosphatidylethanolamine. Thus, although the total membrane lipids from this
      organism form only lamellar phases under physiological conditions, the individual
      membrane lipids appear to exhibit a wide range of phase preferences.
      Phosphatidylglycerol and diglucosyldiacylglycerol seem to have relatively strong
      and weak preferences for the lamellar liquid-crystalline phase, respectively,
      while monoglucosyldiacylglycerol, and especially acyl polyprenyl glucoside,
      strongly prefers the reversed hexagonal phase. Most notable in this regard is the
      phase preference of glycerylphosphoryldiglucosyldiacylglycerol, which strongly
      destabilizes the reversed hexagonal phase and which we show in the accompanying
      paper [Lewis, R. N. A. H., & McElhaney, R. N. (1995) Biochemistry 34, 13818
      13824] actually prefers the normal micellar phase in isolation. The presence of
      normal, lamellar, and reversed phase-preferring lipids in a single membrane has
      important implications for understanding the physical basis of lipid organization
      and biosynthetic regulation in this and possibly in other organisms. We also show
      that the characteristic effect of the individual A. laidlawii membrane lipids on
      the lamellar/reversed hexagonal phase transition temperature of the
      phosphatidylethanolamine matrix is not well correlated with their polar headgroup
      intrinsic volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577975
TI  - Acholeplasma laidlawii B membranes contain a lipid
      (glycerylphosphoryldiglucosyldiacylglycerol) which forms micelles rather than
      lamellar or reversed phases when dispersed in water.
AB  - It has been proposed that each of the lipids from the Acholeplasma laidlawii
      membrane prefers to form either a lamellar or a reversed cubic or hexagonal phase
      when dispersed in excess water at physiologically relevant temperatures and ionic
      strengths. In this study, we have reinvestigated the thermotropic phase behavior
      of all the major membrane lipids from A. laidlawii B membranes derived from cells
      grown in equimolar palmitic and elaidic acids. We confirm that
      phosphatidylglycerol (PG) and diglucosyldiacylglycerol (DGDG) from such membranes
      do indeed form only lamellar phases over the temperature range 5-80 degrees C. We
      also confirm that the monoglucosyldiacylglycerol (MGDG) and acyl polyprenyl
      glucoside (APG) exist in lamellar phases at lower temperatures but do form
      reversed phases at higher temperatures. However, we present here optical,
      differential scanning calorimetric, quasielastic light scattering, and 2H- and
      31P-nuclear magnetic resonance spectroscopic evidence indicating that one lipid
      component of the A. laidlawii B membrane, namely,
      glycerylphosphoryldiglucosyldiacylglycerol (GPDGDG), actually forms normal
      micellar rather than lamellar or reversed phases when dispersed in excess water
      at physiological temperatures. To the best of our knowledge, this is the first
      demonstration of the existence of a micellar phase-preferring lipid in a
      prokaryotic cell membrane, and only the second demonstration of the existence of
      a micellar phase-forming lipid in any biological membrane. We also show that
      GPDGDG levels change greatly depending on the fatty acid composition of the
      membrane lipids of this organism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577976
TI  - Analysis of the ion binding sites of calmodulin by electrospray ionization mass
      spectrometry.
AB  - The binding of Ca2+ and Mg2+ to four calmodulins (SynCaM 1, SynCaM 8, SynCaM 12A,
      and SynCaM 18A) has been studied by ESI-MS. The mass spectra were recorded by
      dissolving the apoproteins in methanol/water (20/80, v/v) containing 1 mM CaCl2
      or 1 mM MgCl2 and the pH adjusted to 6.0 with ammonia. The carrier solvent was
      methanol/water (20/80, v/v). In the case of Ca2+ complexation, ESI-MS reveals the
      presence of three kinds of sites: the first of high affinity corresponding to
      those determined using flow and equilibrium dialysis techniques and two others
      with lower affinities. These results clearly confirm the conclusion of Milos et
      al. [Milos, M., Comte, M., Schaer, J. J., & Cox, J. A. (1989) J. Inorg. Biochem.
      36, 11-25] that there should exist between four and six auxiliary sites for Ca2+.
      Concerning the complexation of magnesium, the four proteins are able to bind two
      Mg2+ almost certainly on auxiliary cationic sites.

PMID- 7577977
TI  - Time-resolved polarized fluorescence spectroscopy studies of plasminogen
      activator inhibitor type 1: conformational changes of the reactive center upon
      interactions with target proteases, vitronectin and heparin.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) is an important physiological
      inhibitor of the plasminogen activator system. To investigate the structure
      functional aspects of this inhibitor, we have taken advantage of the lack of
      cysteine residues in the PAI-1 molecule and substituted Ser344 (P3) and Met347
      (P1'), in the reactive center loop, with cysteines, thereby creating unique
      attachment sites for extrinsic fluorescent probe. Both cysteine mutants were
      purified and labeled with a sulfhydryl specific fluorophore, N-(4,4-difluoro-5,7
      dimethyl-4-bora-3a,4a-diaza-s-indacen yl-3-propionyl)-N-
      (iodoacetyl)ethylenediamine (BDYIA). The labeled mutants were found to reveal
      biochemical characteristics very similar to those of wild type PAI-1. Time
      resolved fluorescence spectroscopy was used to examine orientational freedom of
      BDYIA in the reactive center loop of PAI-1. The orientational freedom of the
      probe was found to be greater in the latent form than in the active form of PAI
      1, suggesting that the reactive center has a more relaxed conformation in the
      latent form than in the active form. Complex formation with target proteases,
      tissue type plasminogen activator (tPA) and urokinase type plasminogen activator
      (uPA), caused decreased orientational freedom of BDYIA in the P3 position, while
      the orientational freedom of BDYIA in position P1' increased to a level similar
      to that of BDYIA in reactive center-cleaved PAI-1. In contrast, complex formation
      with modified anhydro-uPA, which is unable to cleave its substrate, largely
      restricted the orientational freedom of BDYIA probe in the P1' position.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577979
TI  - Phosphorescence lifetime of tryptophan in proteins.
AB  - This investigation enquires into the factors that are responsible for the wide
      range of room-temperature Trp phosphorescence lifetimes (tau) in proteins. By
      exploiting the enhanced sensitivity and time resolution of phosphorescence
      measurements, experiments were conducted to evaluate the triplet quenching
      potential of each amino acid side chain. From the magnitude of the Stern-Volmer
      rate constant it is concluded that, among the amino acids, quenching reactions at
      20 degrees C are quite effective with His, Tyr, Trp, cysteine, and cystine, with
      rate enhancements of 20 and 50 times when the side chains of Tyr and His,
      respectively, are in the ionized form. The distance dependence of the quenching
      interaction, estimated from the quenching of internal Trp residues in proteins
      separated from the amino acid in solution by a protein spacer of various
      thickness, emphasizes the very short-range nature of the process. The importance
      of these side chains, and to some extent that of the peptide linkage, as
      intrinsic quenchers of Trp phosphorescence in proteins was also confirmed with
      short synthetic peptides prepared appositely with only one type of these
      residues. Finally, very short (microseconds) phosphorescence lifetimes of Trp
      residues in proteins were shown to be invariably associated with the presence of
      Tyr or Cys in the immediate neighborhood of the chromophore. From a survey of the
      amino acids that are nearest neighbors to Trp in proteins and the corresponding
      value of tau it was established that, in the absence of His, Tyr, Trp, and Cys,
      tau is > or = 1 ms and appears to reflect mainly the local fluidity of the
      protein structure. Otherwise, tau can be much shorter, and for bulky His, Tyr,
      and Trp side chains it seems to depend dramatically on the mutual chromophore
      quencher orientation. In these cases the triplet decay kinetics is shown to be a
      complex function of temperature, pH, and flexibility of the protein site.

PMID- 7577978
TI  - Binding of Co(III) to a DNA oligomer via reaction of [Co(NH3)5(OH2)]3+ with
      (5medC-dG)4.
AB  - The interaction specificities of cobalt(III) ammines with the self-complementary
      eight-base pair DNA oligomer (5medC-dG)4 have been investigated. Standard
      protocol for preparing DNA samples calls for heat annealing the DNA oligomer in
      phosphate buffer in the absence or presence of cobalt(III) ammine complex for 2
      min at 80 degrees C, followed by slow cooling to 25 degrees C. An alternative
      method for DNA preparation is incubation of the oligomer in the presence of the
      cobalt(III) complex at 37 degrees C followed by exhaustive dialysis. The
      conformational properties of the thus-treated DNA oligomer were determined by
      inspection of the UV and CD spectra at 25 and 95 degrees C and thermal
      denaturation studies. With heat annealing in the absence of any cobalt(III)
      complex, (5medC-dG)4 assumes a double-stranded, right-handed B conformation at 25
      degrees C. Upon heat annealing in the presence of 200 microM [Co(NH3)6]3+, (5medC
      dG)4 assumes a double-stranded, left-handed Z conformation at 25 degrees C. In
      contrast, the CD and UV spectra of (5medC-dG)4 heat annealed in the presence of
      200 microM [Co(NH3)5(OH2)]3+ are consistent with a distorted B-like conformation
      at 25 degrees C. Incubation of the oligomer in the presence of [Co(NH3)5(OH2)]3+
      results in modification of the conformational properties of the oligomer at both
      25 and 95 degrees C relative to the untreated oligomer. The extent of
      modification depends upon the incubation concentration of [Co(NH3)5-(OH2)]3+ and
      the reaction time. Atomic absorption (AA) analyses of these treated DNA samples
      indicate a high degree of cobalt association to the oligomer.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7577980
TI  - NMR studies of the phosphotransfer domain of the histidine kinase CheA from
      Escherichia coli: assignments, secondary structure, general fold, and backbone
      dynamics.
AB  - Multidimensional heteronuclear NMR techniques were applied to study the
      phosphotransfer domain, residues 1-134, of the histidine kinase CheA, from
      Escherichia coli, which contains the site of autophosphorylation, His48.
      Assignments of the backbone amide groups and side chain protons are nearly
      complete. Our studies show that this protein fragment consists of five alpha
      helices (A-E) connected by turns. Analysis of NOE distance restraints provided by
      two-dimensional (2D) 1H-1H and three-dimensional (3D) 15N-edited NOESY spectra
      using model building and structure calculations indicates that the five helices
      form an antiparallel helix bundle with near-neighbor connectivity. The amino
      terminal four helices are proposed to be arranged in a right-handed manner with
      helix E packing against helices C and D. From ideal hydrophobic helical packing
      and structure calculations, the site of autophosphorylation, His48, is nearly
      fully exposed to the solvent. We measured the NMR relaxation properties of the
      backbone 15N nuclei using inverse detected two-dimensional NMR spectroscopy. The
      protein backbone dynamics studies show that CheA1-134 is formed into a tight and
      compact structure with very limited flexibilities both in helices and turns.
      Structural implications of titration and phosphorylation experiments are briefly
      discussed.

PMID- 7577981
TI  - Nuclear magnetic resonance assignments and global fold of a CheY-binding domain
      in CheA, the chemotaxis-specific kinase of Escherichia coli.
AB  - CheA is the histidine autokinase in the Escherichia coli chemotaxis signal
      transduction pathway responsible for coupling of signals received by
      transmembrane receptors to the response regulators CheY and CheB. Here NMR
      spectroscopy is used to study a 14 kDa fragment of CheA, residues 124-257, that
      binds the response regulator CheY. Backbone atom resonance assignments were
      obtained by analysis of 3D HNCACB, 3D CBCA(CO)NH, and HNCO spectra, whereas side
      chain assignments were obtained primarily by analysis of 3D H(CCO)NH, 3D C(CO)NH,
      3D HCCH-TOCSY, and 3D 1H, 15N TOCSY-HSMQC spectra. NOE cross peak patterns and
      intensities as well as torsion angle restraints were used to determine the
      secondary structure, and a low-resolution structure was calculated by hybrid
      distance-geometry simulated annealing methods. The CheA124-257 fragment consists
      of four antiparallel beta strands and two helices, arranged in an "open-faced
      beta-sandwich" motif, as well as two unstructured ends that correspond to domain
      linkers in the full-length protein. The 15N-1H correlation spectrum of 15N
      labeled CheA124-257 bound to unlabeled CheY shows specific localized changes that
      may correspond to a CheY-binding face on CheA.

PMID- 7577983
TI  - Identification of the IMP binding site in the IMP dehydrogenase from
      Tritrichomonas foetus.
AB  - The IMP dehydrogenase from Tritrichomonas foetus has been identified as a
      potential target for antitritrichomonial chemotherapy. The gene encoding this
      enzyme was expressed in transformed Escherichia coli, and the recombinant protein
      was purified to homogeneity with an average yield of 3 mg of protein per liter of
      bacterial culture. Kinetic characterizations verified that the recombinant enzyme
      is in the authentic native state. 6-Cl-IMP, an irreversible inhibitor of the
      enzyme, was found to protect cysteine residue 319 of the enzyme against
      carboxymethylation by iodoacetamide. Radiolabeled IMP was covalently bound to the
      enzyme during the enzyme-catalyzed reaction via the formation of a specific
      adduct with cysteine residue 319. It is thus postulated that the conversion of
      IMP to XMP catalyzed by the IMP dehydrogenase from T. foetus is mediated by a
      nucleophilic attack of cysteine-319 in the enzyme protein to IMP at, most likely,
      its 2-position to facilitate a hydride transfer to NAD, resulting in the
      formation of a covalent intermediate between substrate and enzyme.

PMID- 7577982
TI  - Evidence for electrophilic catalysis in the 4-chlorobenzoyl-CoA dehalogenase
      reaction: UV, Raman, and 13C-NMR spectral studies of dehalogenase complexes of
      benzoyl-CoA adducts.
AB  - This paper reports on the mechanism of substrate activation by the enzyme 4
      chlorobenzoyl coenzyme A dehalogenase. This enzyme catalyzes the hydrolytic
      dehalogenation of 4-chlorobenzoyl coenzyme A (4-CBA-CoA) to form 4-hydroxybenzoyl
      coenzyme A (4-HBA-CoA). The mechanism of this reaction is known to involve attack
      of an active site carboxylate (Asp or Glu side chain) at C(4) of the substrate
      benzoyl ring to form a Meisenheimer complex. Loss of chloride ion from this
      intermediate results in the formation of an arylated enzyme intermediate. The
      arylated enzyme is hydrolyzed to free enzyme plus 4-HBA-CoA by the addition of
      water at the acyl carbon [Yang, G., Liang, P.-H., & Dunaway-Mariano, D. (1994)
      Biochemistry 33, 8527]. The present studies have focused on the activation of the
      4-CBA-CoA for nucleophilic attack by the active site carboxylate group. UV
      visible, 13C-NMR, and Raman spectroscopic techniques were used to monitor changes
      in the distribution of the pi electrons of the benzoyl moiety of benzoyl-CoA
      adducts [substituted at C(4) with methyl (4-MeBA-CoA), methoxy (4-MeOBA-CoA), or
      hydroxyl (4-HBA-CoA) groups or at C(2) or C(3) with a hydroxyl group (2-HBA-CoA
      and 3-HBA-CoA)] resulting from the binding of these ligands to the dehalogenase
      active site. The UV-visible spectra measured for 4-HBA-CoA in aqueous buffer at
      pH 7.5 and in the dehalogenase active site revealed that a large red shift (from
      292 to 373 nm) in the lambda max of the benzoyl moiety occurs upon
      binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577984
TI  - pH, electrolyte, and substrate-linked variation in active site structure of the
      Trp51Ala variant of cytochrome c peroxidase.
AB  - Electronic absorption, MCD, and 1H NMR spectroscopy have been used to
      characterize the structures and linkage relationships of three active site
      states, LS1, HS, and LS2, of the Trp51Ala variant of yeast cytochrome c
      peroxidase (CcP) in the Fe(III) state. In addition, the binding of three
      substrates (styrene, catechol, and guaiacol) to the Fe(III) variant has been
      studied by 1H NMR spectroscopy, and the paramagnetically shifted resonances of
      the cyanide adduct of the variant have been assigned. The heme iron is
      hexacoordinated in all three pH-dependent states of the enzyme. LS1, the dominant
      acidic species, exhibits electronic and MCD spectra indicative of low-spin, bis
      histidine coordination environment for the heme iron. The HS form, which
      dominates at intermediate pH, exhibits electronic, MCD, and 1H NMR spectra
      characteristic of high-spin heme Fe(III) with axial histidyl and water ligands.
      The LS2 species exhibits spectroscopic properties indicative of a bis-histidine,
      low-spin Fe(III) derivative. The equilibrium constants for interconversion of
      these forms of the variant enzyme are highly dependent on ionic strength,
      specific anions, and temperature of the solution, with the HS form stabilized
      relative to the other forms in the presence of several noncoordinating, anionic
      species. Aromatic substrates such as styrene, catechol, and guaiacol affect the
      chemical shifts of the heme substituents of the HS species but not of the LS2
      species. Based on these results, a model is proposed that accounts to a large
      extent for the electrostatic origin of the three forms of the active site of the
      Trp51Ala variant and the mechanisms by which they are differentially stabilized
      in solution.

PMID- 7577986
TI  - P22 Arc repressor: transition state properties inferred from mutational effects
      on the rates of protein unfolding and refolding.
AB  - The kinetics of unfolding and refolding have been measured for a set of Arc
      repressor mutants bearing single amino acid substitutions at 44 of the 53 residue
      positions. Roughly half of the mutations cause significant changes in the
      unfolding and/or refolding rate constants. These substitutions alter the
      hydrophobic core, tertiary hydrogen bonds and salt bridges, and glycines with
      restricted backbone conformations. Overall, the mutations cause larger changes in
      the unfolding rates than the refolding rates, indicating that significantly less
      side-chain information is used between the denatured state and transition state
      than between the transition state and native state. The set of mutants displays
      reasonable Bronsted behavior, suggesting that many native interactions are
      partially formed in the transition state. Taken together, these observations
      suggest that the overall structure of most of the protein must be somewhat native
      like in the transition state but without close, complementary packing of the
      hydrophobic core or good hydrogen bond geometry. Such a transition state is
      inconsistent with a model in which monomers fold to their correct conformations
      and then dock to form the dimer but supports a model in which folding and
      dimerization are concurrent processes.

PMID- 7577985
TI  - The environment of [2Fe-2S] clusters in ferredoxins: the role of residue 45
      probed by site-directed mutagenesis.
AB  - The biochemical and biophysical properties of the Ala45Ser mutant of the [2Fe-2S]
      ferredoxin from vegetative cells of the cyanobacterium Anabaena sp. 7120 are
      described. This novel protein, which incorporates the residue present in many
      higher plant ferredoxins into the analogous position of a typical cyanobacterial
      ferredoxin, was prepared to probe the origin of the characteristic
      spectrochemical and functional differences between the ferredoxins from these two
      sources. The variant protein was produced by site-directed mutagenesis and was
      expressed as the holoprotein in Escherichia coli. Although the UV-vis spectrum of
      the Ala45Ser mutant was indistinguishable from that of the wild-type (WT)
      protein, the circular dichroism (CD) spectrum of the mutant was distinct and
      similar in appearance to that of spinach ferredoxin, which possesses a Ser
      residue at the analogous position. The values of the principal g factors of the
      EPR spectrum of the dithionite-reduced mutant protein differed from those of the
      WT spectrum and resembled those of plant ferredoxins containing serine at
      position 45. Analysis of the mutant EPR spectrum according to the method of
      Blumberg indicated greater covalent interactions between the localized ferrous
      site of the cluster and the protein matrix relative to the WT protein. The
      resonance Raman spectrum of Ala45Ser Anabaena ferredoxin was distinct from the
      spectrum of the WT protein and showed exceptional similarity to the spectrum of
      higher plant ferredoxins, such as spinach ferredoxin. The mutant protein spectrum
      displayed considerably greater deuterium dependent isotope shifts for bands
      ascribed to terminal Fe-S stretching modes than did the WT spectrum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577987
TI  - Regulatory changes in the control of carbamoyl phosphate synthetase induced by
      truncation and mutagenesis of the allosteric binding domain.
AB  - Carbamoyl phosphate synthetase from Escherichia coli catalyzes the synthesis of
      carbamoyl phosphate from bicarbonate, ammonia, and two molecules of MgATP. The
      enzyme is composed of two nonidentical subunits. The small subunit catalyzes the
      hydrolysis of glutamine to glutamate and ammonia. The large subunit catalyzes the
      formation of carbamoyl phosphate and has the binding sites for bicarbonate,
      ammonia, MgATP, and the allosteric ligands IMP, UMP, and ornithine. The
      allosteric ligands are believed to bind to the extreme C-terminal portion of the
      large subunit. Truncation mutants were constructed to investigate the allosteric
      binding domain. Stop codons were introduced at various locations along the carB
      gene in order to delete amino acids from the carboxy-terminal end of the large
      subunit. Removal of 14-119 amino acids from the carboxy-terminal end of the large
      subunit resulted in significant decreases in all of the enzymatic activities
      catalyzed by the enzyme. A 40-fold decrease in the glutamine-dependent ATPase
      activity was observed for the delta 14 truncation. Similar losses in activity
      were also observed for the delta 50, delta 65, delta 91, and delta 119 mutant
      proteins. However, formation of carbamoyl phosphate was detected even after the
      deletion of 119 amino acids from the carboxy-terminal end of the large subunit.
      No allosteric effects were observed for UMP with either the delta 91 or delta 119
      truncation mutants, but alterations in the catalytic activity were observed in
      the presence of ornithine even after the removal of the last 119 amino acids from
      the large subunit of CPS. Six conserved amino acids within the allosteric domain
      were mutated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577988
TI  - Residual structure in urea-denatured chaperonin GroEL.
AB  - The urea denaturation of the chaperonin GroEL has been studied by circular
      dichroism, intrinsic tyrosine fluorescence and fluorescence of the hydrophobic
      probe, 1,1'-bis(4-anilino)naphthalene-5,5'-disulfonic acid (bisANS). It is shown
      that GroEL denaturation, monitored by CD and intrinsic fluorescence measurements,
      can be well described by a two-state transition that is complete by 3-3.1 M urea.
      The beginning of this transition overlaps the urea concentrations where the
      oligomeric protein starts to dissociate into individual monomers. Subsequent
      addition of the denaturant leads to complete unfolding of the monomers. Monomers
      unfolded at urea concentrations higher than 3.1 M are not competent to form their
      native conformations under the conditions employed here, and they are not able to
      reassemble to oligomers upon dilution of urea. In contrast to the CD and
      intrinsic fluorescence measurements, bisANS bound to GroEL exhibits considerable
      fluorescence intensity under conditions where the CD and intrinsic fluorescence
      signals have already reached their minimum values (> 3.1 M urea). This binding of
      bisANS, under conditions where the majority of the secondary structure of GroEL
      has already unfolded, indicates the existence of hydrophobic residual structure.
      This structure cannot be detected by CD measurements, but it can be unfolded by
      raising further the urea concentration. The existence of this structure does not
      depend on the source or method of the protein preparation. Intrinsic fluorescence
      and trypsin digestion demonstrate no difference between the bisANS-bound form of
      GroEL and the free form of the protein, showing that the GroEL structure is not
      greatly affected by the interaction with bisANS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577989
TI  - Probing intradomain and interdomain conformational changes during equilibrium
      unfolding of phosphoglycerate kinase: fluorescence and circular dichroism study
      of tryptophan mutants.
AB  - Phosphoglycerate kinase is a monomeric protein composed of two globular domains
      of the alpha/beta type. Extensive domain-domain interactions involve three
      segments of the polypeptide chain that are distant from one another in the
      primary sequence: the N-terminus, the C-terminus, and a centrally located alpha
      helix. In order to monitor spectroscopically the conformational changes that
      occur in the individual domains and at the interdomain interface during the
      unfolding process, we have constructed a series of single-tryptophan mutants. In
      addition to two previously described mutants, each with single tryptophans in the
      C-terminal domain (W308 and W333) [Szpikowska, B. K., Beechem, J. M., Sherman, M.
      A., & Mas, M. T. (1994) Biochemistry 33, 2217-2225], four new single-tryptophan
      mutants have been constructed: two with tryptophans located in the interdomain
      region (W194 and W399) and two with tryptophans in the N-terminal domain (W48 and
      W122). The equilibrium unfolding transitions induced by guanidine hydrochloride
      were monitored using far-UV CD, near-UV CD, steady-state, and time-resolved
      fluorescence. These studies reveal two unfolding transitions and suggest a
      sequential unfolding process for the mutants described in this paper. During the
      first transition (Cm approximately 0.5 M) the interdomain region and C-terminal
      domain unfold; the N-terminal domain remains relatively compact but lacks much of
      the tertiary structure that characterizes the native state. A hyperfluorescent
      intermediate is detected during this transition by tryptophan probes placed
      within the N-terminal domain. Complete unfolding of the N-terminal domain occurs
      during the second transition (Cm approximately 0.9 M).

PMID- 7577990
TI  - Sequential domain unfolding in phosphoglycerate kinase: fluorescence intensity
      and anisotropy stopped-flow kinetics of several tryptophan mutants.
AB  - Stopped-flow total intensity and anisotropy experiments on single tryptophan
      containing mutants of yeast phosphoglycerate kinase (PGK) located in either the
      carboxy-terminal domain (W308 and W333), amino-terminal domain (W48 and W122), or
      "hinge" region (W194 and W399) were performed. The results obtained for single
      tryptophans in individual domains suggest that the unfolding of PGK by
      guanidinium hydrochloride is a sequential process in which unfolding of the
      carboxy-terminal domain is followed by the unfolding of the amino-terminal
      domain. A kinetic intermediate has been detected which consists of an unfolded
      carboxy-terminal domain and an altered amino-terminal domain, identical in
      hydrodynamic properties with the native state, but hyperfluorescent. In contrast
      to the C-terminal tryptophans, which exhibit concurrent total intensity and
      anisotropy changes in the entire denaturant concentration range (0-->2 M), the N
      terminal tryptophans experience a large increase in fluorescence intensity and a
      constant anisotropic environment at low concentrations of denaturant,
      corresponding to the first transition region of the equilibrium unfolding
      profile. Anisotropy changes for the N-terminal probes are observed above 1 M Gdn
      HCl, the region corresponding to the second equilibrium unfolding transition.
      Stopped-flow experiments performed on PGK mutants with two tryptophans (i.e.,
      with a single tryptophan in each domain) confirm that each domain unfolds
      independently, and that the individual site-specific mutations do not
      significantly alter the unfolding pathway. Unfolding kinetics experiments with
      tryptophans situated in the hinge reveal that the region sensed by W399 unfolds
      before the carboxy-terminal domain, whereas W194 senses unfolding of both
      domains.

PMID- 7577992
TI  - Binding modes for substrate and a proposed transition-state analogue of protozoan
      nucleoside hydrolase.
AB  - The transition-state structure for inosine-uridine nucleoside hydrolase (IU
      nucleoside hydrolase) from Crithidia fasciculata is characterized by oxycarbonium
      character in the ribosyl and weak bonds to the departing hypoxanthine and
      incipient water nucleophile [Horenstein, B. A., Parkin, D. W., Estupinan, B., &
      Schramm, V. L. (1991) Biochemistry 30, 10788-10795]. Inhibitors designed to
      resemble the transition state are slow-onset, tight-binding inhibitors with
      observed Km/Ki values up to 2 x 10(5) [Schramm, V. L., Horenstein, B. H., &
      Kline, P. C. (1994) J. Biol. Chem. 269, 18259-18262]. Although slow-onset, tight
      binding is consistent with transition-state stabilization, more direct evidence
      can be obtained by comparing the groups which interact with the substrate to
      provide binding and catalysis with those which interact with the putative
      transition-state inhibitor. The Km value for inosine binding to IU-nucleoside
      hydrolase is independent of pH over the range 5.6-10.5. Dependencies of Vmax and
      Vmax/Km on pH result in pH optima near 8.0. A single group with pK of 9.1 must be
      protonated for catalytic activity, and protonation of a second group with a pK of
      7.1 results in loss of activity. 1-(S)-Phenyl-1,4-dideoxy-1,4-imino-D-ribitol
      (phenyliminoribitol) binds with an equilibrium Kd of 30 nM and has been proposed
      to be a transition-state inhibitor. The pH dependence for the competitive
      inhibition by phenyliminoribitol resembles the Vmax profile with the protonation
      of a single group, pK 7.5, required for inhibitor binding and the protonation of
      a subsequent group, pK 6.6, causing loss of binding.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577991
TI  - Energetic contribution of side chain hydrogen bonding to the stability of
      staphylococcal nuclease.
AB  - Hydrogen bonds are a ubiquitous feature of protein structures, yet there is great
      uncertainty about the energetic contribution of hydrogen bonding to protein
      stability. This study addresses this question by making a series of single
      substitution mutations in the model protein staphylococcal nuclease. These
      mutants have had a residue capable of participating in hydrogen bonding either
      removed or introduced. The variants we have investigated are as follows: nine
      valines substituted with threonine and serine; eight threonines converted to
      valine, serine, and cysteine; and seven tyrosines replaced by phenylalanine and
      leucine. The stabilities of these 56 mutant proteins were determined by titration
      with guanidine hydrochloride using fluorescence as a probe of structure. In
      general, it was found that the stability effects of removing a hydrogen bonding
      residue and replacing it with a nonbonding residue were relatively small. This
      was true even in the case of buried residues participating in hydrogen bonds,
      where the substituted residue leaves an unfulfilled hydrogen bond in the
      hydrophobic core. In contrast, introducing a hydrogen bonding residue in place of
      a nonbonding residue was generally more costly energetically. A wide variability
      in the cost of burying a hydroxyl was observed, but this does not seem to be due
      to differences in hydrogen bonding. The overall energetic contribution of various
      wild-type hydrogen bonding interactions was evaluated as being favorable. A range
      of energies from approximately 1.5 to 4.0 kcal/mol was estimated for the
      contribution of these interactions to the stability of the native state.

PMID- 7577993
TI  - Crystallographic analysis of reversible metal binding observed in a mutant
      (Asp153-->Gly) of Escherichia coli alkaline phosphatase.
AB  - Here we present the refined crystal structures of three different conformational
      states of the Asp153-->Gly mutant (D153G) of alkaline phosphatase (AP), a
      metalloenzyme from Escherichia coli. The apo state is induced in the crystal over
      a 3 month period by metal depletion of the holoenzyme crystals. Subsequently, the
      metals are reintroduced in the crystalline state in a time-dependent reversible
      manner without physically damaging the crystals. Two structural intermediates of
      the holo form based on data from a 2 week (intermediate I) and a 2 month soak
      (intermediate II) of the apo crystals with Mg2+ and Zn2+ have been identified.
      The three-dimensional crystal structures of the apo (R = 18.1%), intermediate I
      (R = 19.5%), and intermediate II (R = 19.9%) of the D153G enzyme have been
      refined and the corresponding structures analyzed and compared. Large
      conformational changes that extend from the mutant active site to surface loops,
      located 20 A away, are observed in the apo structure with respect to the holo
      structure. The structure of intermediate I shows the recovery of the entire
      enzyme to an almost native-like conformation, with the exception of residues Asp
      51 and Asp 369 in the active site and the surface loop (406-410) which remains
      partially disordered. In the three-dimensional structure of intermediate II, both
      Asp 51 and Asp 369 are essentially in a native-like conformation, but the main
      chain of residues 406-408 within the loop is still not fully ordered. The D153G
      mutant protein exhibits weak, reversible, time dependent metal binding in
      solution and in the crystalline state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577994
TI  - Extensive nonrandom structure in reduced and unfolded bovine pancreatic trypsin
      inhibitor.
AB  - Two-dimensional 1H NMR spectra of an analog of reduced BPTI at pH 4.5, 1 degrees
      C, have been assigned. Spectra indicate considerable conformational averaging, as
      expected for a flexible, unfolded protein. The presence of extensive nonrandom
      structure is detected by the presence of NHi-NHi + 1 and aromatic-aliphatic NOEs.
      Sequential amide-amide NOEs indicate that turn-like conformations are
      significantly populated at 18 pairs of residues along the chain. Many of these
      are located in a turn, loop, or helix in native BPTI, but six are observed for
      contiguous pairs in the segment composed of residues 29-35, which in native BPTI
      constitute a strand of extended sheet. A novel finding for unfolded proteins is
      our observation of NOEs implying non-native hydrophobic interactions. Multiple
      aromatic-aliphatic NOEs are observed for pairs of residues that are within 1-3
      residues of each other. Most are non-native and involve residues in both strands
      of the central antiparallel strand-turn-strand of native BPTI comprised of
      residues 18-35. All NOEs reported for oligopeptides spanning the BPTI sequence
      [Kemmink, J., & Creighton, T. (1993) J. Mol. Biol. 234, 861-878] are observed in
      reduced BPTI, but many others are present as well. Similar spectra are obtained
      for naturally occurring BPTI reduced by dithiothreitol, BPTI with cysteines
      replaced by alpha-amino-n-butyric acid, and BPTI mutant F45A reduced by
      dithiothreitol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7577995
TI  - Nature of the transition state of the protein-tyrosine phosphatase-catalyzed
      reaction.
AB  - The dephosphorylation of p-nitrophenyl phosphate by Yersinia protein-tyrosine
      phosphatase (PTPase) and by the rat PTP1 has been examined by measurement of
      heavy-atom isotope effects at the nonbridge oxygen atoms [18(V/K)nonbridge], at
      the bridging oxygen atom [18(V/K)bridge], and the nitrogen atom in the leaving
      group 15(V/K). The effects were measured using an isotope ratio mass spectrometer
      by the competitive method and thus are effects on V/K. The results for the
      Yersinia PTPase and rat PTP1, respectively, are 1.0142 +/- 0.0004 and 1.0152 +/-
      0.0006 for 18(V/K)bridge; 0.9981 +/- 0.0015 and 0.9998 +/- 0.0013 for
      18(V/K)nonbridge; and 1.0001 +/- 0.0002 and 0.9999 +/- 0.0003 for 15(V/K). The
      magnitudes of the isotope effects are similar to the intrinsic values measured in
      solution, indicating that the chemical step is rate-limiting for V/K. The
      transition state for phosphorylation of the enzyme is dissociative in character,
      as is the case in solution. Binding of the substrate is rapid and reversible, as
      is the binding-induced conformational change which brings the catalytic general
      acid into the active site. Cleavage of the P-O bond and proton transfer from the
      general acid Asp to the leaving group are both far advanced in the transition
      state, and there is no development of negative charge on the departing leaving
      group. Experiments with several general acid mutants give values for
      18(V/K)bridge of around 1.0280, 15(V/K) of about 1.002, and 18(V/K)nonbridge
      effects of from 1.0007 to 1.0022. These data indicate a dissociative transition
      state with the leaving group departing as the nitrophenolate anion but suggest
      more nucleophilic participation than in the solution reaction.

PMID- 7577996
TI  - Phosphatidylethanolamine augments factor VIIa-tissue factor activity: enhancement
      of sensitivity to phosphatidylserine.
AB  - The effect of phosphatidylethanolamine (PE) on the activity of the factor VIIa
      tissue factor complex (fVIIa-TF) has been examined with respect to plasma
      clotting activity and activation of factor X (fX) in a purified system. Vesicles
      prepared by relipidating membrane-anchored TF (dcTF; TF1-244, lacking the C
      terminal cytoplasmic tail) into phospholipid vesicles containing 6 mol %
      phosphatidylserine (PS) and increasing levels of PE up to 40 mol % (the balance
      consisting of phosphatidylcholine) were found to progressively shorten TF
      initiated clotting in normal human plasma to levels comparable to those observed
      using dcTF relipidated with cephalin. The shortened clotting times were at least
      in part due to the ability of PE-containing membranes to better support the
      activation of fX by the fVIIa.TF complex, as vesicles with increased PE content
      yielded progressively higher initial rates of fX activation. Surprisingly, PE
      substantially altered the sensitivity of fX activation to low levels of PS,
      yielding near-maximal rates of activation at only 3 mol % PS compared to 15-20
      mol % PS required in the absence of PE. The effect of PE was not synergistic with
      that of PS since PE did not increase fX activation rates at high levels of PS (20
      mol %). Examination of the kinetic parameters for fX activation revealed that the
      majority of the effect of PE was in decreasing the apparent Km for fX.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7577997
TI  - Distribution of the thiamin diphosphate C(2)-proton during catalysis of
      acetaldehyde formation by brewers' yeast pyruvate decarboxylase.
AB  - The distribution of tritium derived from enzyme-bound [thiazole-2-T]thiamin
      diphosphate (TDP) during the reaction of pyruvate to form acetaldehyde catalyzed
      by pyruvate decarboxylase isozymes (PDC; EC 4.1.1.1) from Saccharomyces
      carlsbergensis was determined under single-turnover conditions ([E] > [S]) in the
      presence of the nonsubstrate allosteric effector pyruvamide. The specific
      radioactivity of the [1-L]acetaldehyde product and solvent ([L]H2O) was 43 +/- 4%
      and 54 +/- 2%, respectively, of the initial specific radioactivity of PDC-bound
      [thiazole-2-T]TDP and was independent of the extent of the single-turnover
      reaction. There is little (< or = 3%) or no return of the abstracted C(2)-hydron
      to the C(2) position of PDC-bound TDP. This provides evidence that the abstracted
      C(2)-hydron is involved in the specific protonation of the C(alpha) position of
      the PDC-bound intermediate 2-(1-hydroxyethyl)thiamin diphosphate (HETDP), which
      is cleaved to form [1-L]acetaldehyde and PDC-bound [thiazole-2-H]TDP. The partial
      exchange of C(2)-derived tritium into solvent requires that (1) hydron transfer
      from C(2) occurs to a catalytic-base in which the conjugate catalytic acid is
      partially shielded from hydron exchange with the solvent, (2) the conjugate
      catalytic acid transfers the C(2)-derived hydron to the C(alpha) position of
      HETDP, and (3) hydron transfer to C(2) to regenerate the coenzyme occurs either
      from solvent directly or from a second catalytic acid of the enzyme that
      undergoes rapid hydron exchange with the solvent.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7577999
TI  - Structure determination and analysis of human neutrophil collagenase complexed
      with a hydroxamate inhibitor.
AB  - Matrix metalloproteinases are a family of zinc endopeptidases involved in tissue
      remodeling. They have been implicated in various disease processes including
      metastasis, joint destruction, and neurodegeneration. Human neutrophil
      collagenase (HNC, MMP-8) represents one of the three "interstitial" collagenases
      that cleave triple-helical collagens types I, II, and III. Its 163-residue
      catalytic domain (Met80 to Gly242) has been expressed in Escherichia coli and
      crystallized as a noncovalent complex with the hydroxamate inhibitor batimastat.
      The crystal structure, refined to 2.1 A, demonstrates that batimastat binds to
      the S1-S2' sites and coordinates to the catalytic zinc in a bidentate manner via
      the hydroxyl and carbonyl oxygens of the hydroxamate group. The batimastat
      collagenase complex is described in detail, and the activities of batimastat
      analogues are discussed in the light of the protein-inhibitor interactions
      revealed by the crystallography studies.

PMID- 7577998
TI  - Solvent-derived protons in catalysis by brewers' yeast pyruvate decarboxylase.
AB  - Catalysis of proton transfer to thiamin diphosphate (TDP) and 2-(1
      hydroxyethyl)thiamin diphosphate (HETDP) by pyruvate decarboxylase isozymes (PDC;
      EC 4.1.1.1) from Saccharomyces carlsbergensis was investigated by determining the
      solvent discrimination tritium isotope effect, (kH/kT)disc, on the reaction of
      pyruvate to form acetaldehyde in the presence of the nonsubstrate allosteric
      effector pyruvamide. The fractionation factors for TDP C(2)-L (phi C(2) = 0.98 +/
      0.06) and HETDP C(alpha)-L (phi C(alpha) = 1.01 +/- 0.07) (L = H or D) do not
      contribute significantly to observed enzymic isotopic discrimination. The value
      of (kH/kT)disc = 1.0 for reprotonation of TDP C(2)-L under single-turnover
      conditions ([E] > [S]) is consistent with C(2)-hydron transfer via a catalytic
      group (phi = 1) equilibrated with solvent. [1-L]Acetaldehyde formation under
      transient steady-state ([E] < [S]) conditions shows solvent discrimination
      tritium isotope effects that increase over the range (kH/kT)disc = 0.39 (single
      turnover) to 0.86 (ten turnovers). The 2-fold increase in the value of
      (kH/kT)disc for the [1-L]acetaldehyde product under steady-state compared to
      single-turnover conditions is attributed to a fractionation factor of phi 1 =
      0.88 +/- 0.06 for the residue(s) involved in C(alpha)-hydron transfer to form
      HETDP. This provides evidence that catalysis of acetaldehyde formation by PDC
      involves specific protonation of both HETDP C(alpha)-L and TDP C(2)-L (phi 2 =
      1.0 +/- 0.1) and requires at least two catalytic groups. Values of phi < or = 1
      for protonation of TDP C(2)-L and HETDP C(alpha)-L provide no evidence that the
      exocyclic 4'-amino or -imino group (phi > or = 1.2) provides significant
      intramolecular catalysis in the enzyme-bound coenzyme.

PMID- 7578000
TI  - Major groove (R)-alpha-(N6-adenyl)styrene oxide adducts in an
      oligodeoxynucleotide containing the human N-ras codon 61 sequence: conformations
      of the R(61,2) and R(61,3) sequence isomers from 1H NMR.
AB  - Conformations of (R)-alpha-(N6-adenyl)styrene oxide adducts at positions X6 in
      d(CGGACXAGAAG).d(CTTCTTGTCCG) and X7 in d(CGGACAXGAAG).d(CTTCTTGTCCG),
      incorporating codons 60, 61 (underlined), and 62 of the human n-ras
      protooncogene, were refined from 1H NMR data. These were the R(61,2) and R(61,3)
      adducts. Chemical shift perturbations were in the 5'-direction from the sites of
      adduction; large changes were observed for C5 H5 and H6 in the R(61,2) adduct.
      The styrene moieties were only partially defined by NOE data. Spectral overlap,
      particularly for the R(61,2) adduct, prevented complete assignments of the
      aromatic resonances; likewise, there were insufficient data to orient the CH2OH
      moieties. Ring flips were slow on the NMR time scale. For the R(61,2) adduct 260
      restraints were obtained from NOE data at three mixing times using relaxation
      matrix analysis; for the R(61,3) adduct 230 restraints were obtained. Structures
      emergent from molecular dynamics/simulated annealing for the R(61,2) adduct
      converged to average and maximum pairwise rms differences of 1.3 and 1.7 A,
      respectively, while those for the R(61,3) adduct converged to average and maximum
      pairwise rms differences of 1.2 and 1.6 A. Sixth root residual indices of 7.5 and
      6.8 x 10(-2) were measured between the refined structures and NOE intensities
      using relaxation matrix calculations for the R(61,2) and R(61,3) adducts,
      respectively. The styrene rings were in the 5'-direction from the lesion sites in
      the major groove. The preferred orientation calculated for the R(61,2) adduct
      placed the styrene ring edgewise and approximately orthogonal to C5, while that
      calculated for the R(61,3) duplex had the styrene ring approximately orthogonal
      to the major groove edges of base pairs A6.T17 and R-SOA7.T16.

PMID- 7578001
TI  - Refined solution structure of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1
      opposite CpA in the complementary strand of an oligodeoxynucleotide duplex as
      determined by 1H NMR.
AB  - The solution structure of d(CCATCAFBGATCC).d(GGATCAGATGG), containing the 8,9
      dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 adduct, was refined using molecular
      dynamics restrained by NOE data obtained from 1H NMR. The modified guanosine was
      positioned opposite cytosine, while the aflatoxin moiety was positioned opposite
      adenosine in the complementary strand. Sequential 1H NOEs were interrupted
      between C5 and AFBG6, but intrastrand NOEs were traced through the aflatoxin
      moiety, via H6a of aflatoxin and H8 of the modified guanine. Opposite the lesion,
      the NOE between A16 H1' and G17 H8 was weak. A total of 43 NOEs were observed
      between DNA protons and aflatoxin protons. Molecular dynamics calculations
      restrained with 259 experimental and empirical distances, and using sp2
      hybridization at AFBG6 N7, refined structures with pairwise rms differences <
      0.85 A, excluding terminal base pairs. Relaxation matrix calculations yielded a
      sixth root rms difference between refined structures and NOE intensity data of
      7.3 x 10(-2). The aflatoxin moiety intercalated on the 5'-face of the modified
      guanine. The extra adenine A16 was inserted between base pair AFBG6.C15 and the
      aflatoxin moiety. A 36 degree bending between the plane of base pair AFBG6.C15
      and the plane of the aflatoxin moiety was predicted. The aflatoxin moiety stacked
      below the top domain of the oligodeoxynucleotide, which consisted of base pairs
      C1.G21, C2.G20, A3.T19, T4.A18, and C5.G17. The bottom domain consisted of base
      pairs AFBG6.C15, A7.T14, T8.A13, C9.G12, and C10.G11. The average winding angle
      between base pair C5.G17, the intercalated aflatoxin moiety, A16, and base pair
      AFBG6.C15 was reduced to 10 degrees. The preponderance of base pair substitutions
      in the aflatoxin B1 mutational spectrum, particularly G-->T transversions,
      suggests that the stability of this modified oligodeoxynucleotide, which models a
      templated +1 addition mutation, does not reliably predict the frequency of frame
      shifts.

PMID- 7578002
TI  - Sequence-directed single strand cleavage of DNA by a netropsin-flavin hybrid
      molecule.
AB  - In an attempt to obtain sequence specific DNA-cleaving molecules, we have
      synthesized a series of hybrid minor groove binders composed of a photoactiveable
      isoalloxazine (flavin) chromophore linked through a polymethylenic chain to a bis
      pyrrolecarboxamide moiety related to netropsin. Like netropsin, the hybrid
      derivatives preferentially bind to A+T-rich sequences. Activation of the flavin
      chromophore by visible light results in the appearance of single strand breaks in
      the vicinity of the DNA binding site. We have further investigated the cleavage
      affinity properties of one of these compounds referred to as netropsin-flavin
      (Net-Fla) and considered as representative of the series. Net-Fla cleaves only
      one strand at a specific locus downstream of 5'-AAAT-3', upstream of 5'-TAAA-3'
      and on either side of a 5'-AAAA-3' sequence. Net-Fla cleaves both strands
      downstream to 5'-AATT-3'. This makes the properties of Net-Fla similar to that of
      a restriction endonuclease and provides additional insight into establishing the
      rules for the readout of B-DNA helix by non-nucleotidic compounds. Using
      molecular modeling, we show that Net-Fla binds to an asymmetric site in one
      orientation. The values of the energetic minima lie in the same order as expected
      from the cleavage patterns, which suggests that the oriented cleavage is a
      consequence of a sequence-oriented binding of Net-Fla in the DNA minor groove.

PMID- 7578003
TI  - Chiral recognition of deoxyoligonucleotides by delta- and lambda
      tris(ethylenediamine)cobalt(III).
AB  - 59Co NMR and CD measurements show for both stereoisomers of Co(en)3(3+) a similar
      trend in the sequence dependence of DNA recognition, as was reported previously
      for Co(NH3)6(3+). In particular, specific binding is evident to DNA molecules
      possessing runs of two or more same-strand guanine residues. The binding of
      either isomer to such sequences induces structural transitions toward A-DNA
      characteristics. Such measurements also show significant differences between the
      two stereoisomers in terms of how they recognize specific duplex DNA sequences.
      delta-Co(en)3(3+) binds more tightly than lambda-Co(en)3(3+) to right-handed,
      guanine-rich DNA, whereas lambda-Co(en)3(3+) binds more tightly than delta
      Co(en)3(3+) to left-handed DNA. The two stereoisomers bind in an
      indistinguishable manner to AT-rich DNA.

PMID- 7578004
TI  - Purification and characterization of toluene 2-monooxygenase from Burkholderia
      cepacia G4.
AB  - Recent in vivo studies indicate that ring monooxygenation is a widespread
      mechanism by which bacteria metabolize aromatic hydrocarbons and obtain carbon
      and energy. In this study, toluene 2-monooxygenase from Burkholderia (formerly
      Pseudomonas) cepacia G4 was purified to homogeneity and found to be a three
      component enzyme system. The reconstituted enzyme system oxidized toluene to o
      cresol and o-cresol to 3-methylcatechol, an important intermediate for growth of
      the bacterium on toluene. Steady-state kinetic parameters measured for the water
      soluble substrate o-cresol were a Km of 0.8 microM and a Vmax of 131 nmol min-1
      (mg of hydroxylase protein)-1. The three protein components were (1) a 40 kDa
      polypeptide containing one FAD and a [2Fe2S] cluster, (2) a 10.4 kDa polypeptide
      that contained no identifiable metals or organic cofactors, and (3) a 211 kDa
      alpha 2 beta 2 gamma 2 component containing five to six iron atoms. The 40 kDa
      flavo-iron-sulfur protein oxidized NADH and transferred electrons to cytochrome
      c, dyes, and the alpha 2 beta 2 gamma 2 component. It is analogous to other NADH
      oxidoreductase components found in a wide range of bacterial mono- and
      dioxygenases. The 10.4 kDa component, added to the other two components and NADH,
      increased toluene oxidation rates 10-fold. The alpha 2 beta 2 gamma 2 component
      was indicated to contain the site for toluene binding and hydroxylation by the
      following observations: (1) tight binding to a toluene affinity column; (2)
      oxidation of toluene after reduction of the protein with dithionite and adding
      O2; (3) H2O2-dependent toluene oxidation and catalase activity; and (4)
      spectroscopic studies of the iron atoms in the component. The alpha 2 beta 2
      gamma 2 component had no significant absorbance in the visible region. EPR
      spectroscopy yielded a signal at g = 16 upon addition of > 2 equiv of electrons
      per 2 Fe atoms. Taken with the quantitation of five to six iron atoms, the data
      suggest that the alpha 2 beta 2 gamma 2 component contains two binuclear iron
      centers. In total, the structural, spectroscopic, and catalytic features of
      toluene 2-monooxygenase are reminiscent of soluble methane monooxygenase obtained
      from methanotrophic bacteria. The two enzyme systems also differ in many subtle
      ways; for example, they oxidize toluene with completely different
      regiospecificity.

PMID- 7578005
TI  - Nature of rate-limiting steps in the soybean lipoxygenase-1 reaction.
AB  - A series of kinetic isotope effect experiments were performed with the goal of
      understanding the nature of rate-limiting steps in the soybean lipoxygenase-1
      (SBL-1) reaction. SBL-1 was reacted with linoleic acid (LA) and deuterated
      linoleic acid (D-LA) under a variety of experimental conditions involving changes
      in temperature, pH, viscosity, and replacement of H2O with D2O. The extrapolated
      intrinsic primary H/D isotope effect can be estimated to be possibly as large as
      80. This value is probably the largest isotope effect published for an enzymatic
      reaction, and much larger than that predicted from semiclassical models. Due to
      this large primary isotope effect, the C-D bond cleavage fully limits the rate of
      reaction under all conditions tested. In the case of protonated linoleic acid, a
      number of steps are partially rate-limiting at room temperature; three distinct
      mechanistic steps which include substrate binding, an H2O/D2O sensitive step, and
      C-H bond cleavage have been characterized. Use of glucose as a solvent viscosogen
      demonstrates that substrate binding is approximately 48% rate-limiting for LA at
      20 degrees C. SBL-1 is one of the few enzymes that fit the definition of a
      "perfect enzyme", in the sense that further optimization of any single step at
      room temperature will not significantly increase the overall rate. At lower
      temperatures, the step sensitive to solvent deuteration begins to dominate the
      reaction, whereas at higher temperatures, the hydrogen abstraction step is rate
      limiting. The pH dependence of kcat/Km for SBL-1 can be explained as arising from
      two pKa's, one controlling substrate binding and the other substrate release.
      Below pH 7.8, the rate of substrate release increases, thus decreasing the
      commitment to catalysis and unmasking the large intrinsic isotope effect on the
      subsequent hydrogen abstraction. An abnormally high pKa, in the range of 7-8, has
      been determined for LA in the concentration range employed in these studies. We
      propose that the negatively charged form of LA, predominating above pH 7.8, is
      the preferred substrate with larger commitments to catalysis.

PMID- 7578006
TI  - Electron transfer properties of the R2 protein of ribonucleotide reductase from
      Escherichia coli.
AB  - The enzyme ribonucleotide reductase from Escherichia coli consists of two
      proteins, R1 and R2. The active R2 protein contains two dinuclear iron centers
      and the catalytically essential tyrosyl radical. We have explored the redox
      properties of the tyrosyl radical and estimate an apparent redox potential of
      +1000 +/- 100 mV (vs SHE) on the basis of the behavior of numerous mediators. The
      inability of most of these mediators to equilibrate with the tyrosyl radical
      supports the notion that the radical exists in an extremely protected hydrophobic
      pocket that prevents most radical scavengers from interacting with the radical,
      resulting in its unusual stability. The formal midpoint potential of the diiron
      clusters of the R2 protein was determined to be -115 +/- 2 mV at pH 7.6 and 4
      degrees C. This reduction is a two-electron transfer process, making the R2
      protein the first of the nonheme diiron proteins not to stabilize a mixed valence
      intermediate at ambient temperature. The formal midpoint potential of the
      dinuclear iron centers is pH dependent, exhibiting a 30 mV/pH unit variance,
      which indicates that one proton is accepted from the solvent per two electrons
      transferred to the dinuclear iron center upon reduction. The midpoint potential
      of the site-directed mutant Y122F R2 protein was also investigated under the same
      conditions, and this midpoint potential was determined to be -178 mV, providing
      the first direct evidence that the presence of the Y122 residue modulates the
      redox properties of the diiron clusters. The redox potentials of both the wild
      type and Y122F proteins experience cathodic shifts when measured in the presence
      of azide or the R1 protein. For the latter, the midpoint potentials were
      determined to be -226 mV for the wild type protein and -281 mV for the Y122F
      mutant protein, representing a negative shift of over 100 mV for both proteins.
      These results indicate that the presence of the Y122 residue does not influence
      the effect of R1 binding, that the R1 protein preferentially binds the oxidized
      form of R2, and that the binding of R1 acts as a regulatory control mechanism to
      prevent unnecessary turnover of the dinuclear iron centers.

PMID- 7578007
TI  - Mechanistic kinship between hydroxylation and desaturation reactions: acyl-carbon
      bond cleavage promoted by pig and human CYP17 (P-450(17)alpha; 17 alpha
      hydroxylase-17,20-lyase).
AB  - Using homogeneous pig and recombinant human CYP17, the mechanism of the acyl
      carbon bond fission involved in the direct cleavage of pregnenolone was studied.
      It was found that the formation of androsta-5,16-dien-3 beta-ol (5,16-diene) and
      androst-5-ene-3 beta,17 alpha-diol (17 alpha-hydroxyandrogen) from pregnenolone
      was catalyzed by both the isoforms and that the two conversions were dependent on
      the presence of cytochrome b5 (cyt b5). 3 beta-Hydroxyandrost-5-ene-17 beta
      carbaldehyde (aldehyde), an analogue of the physiological substrate pregnenolone,
      was handled as a substrate by both isoforms of CYP17. The aldehyde underwent
      cleavage to produce the 5,16-diene plus the 17 alpha-hydroxyandrogen, at rates
      approximately 8- and 3-fold higher than any physiological reaction catalyzed, in
      the absence of cytochrome b5, by the pig and human CYP17 isoforms, respectively.
      The stereochemistry of the reaction was studied using the aldehyde labeled with
      2H at three strategic positions, 16 alpha, 16 beta, and 17 alpha, with
      incubations performed under both 16O2 and 18O2. The results showed that the
      formation of the 5,16-diene is attended by the removal of the 16 alpha-hydrogen
      atom; all three 2H atoms are retained in the formation of 17 alpha
      hydroxyandrogen and its 17 alpha-hydroxyl oxygen originates from O2. Irrespective
      of the nature of the substrate, or the enzymic conditions used, the 5,16-diene
      and 17 alpha-hydroxyandrogen were produced in similar ratios, suggesting that
      their genesis is closely linked. Both the compounds may be envisaged to arise
      from a peroxy adduct that fragments to give a carbon radical that then undergoes
      either a disproportionation or an oxygen-rebound reaction. The conclusion was
      supported by isotope-partitioning experiments when the conversion of a mixture of
      the unlabeled aldehyde and its isotopomer, containing 2H at 16 alpha as well as
      16 beta, led to the enrichment of 2H in 17 alpha-hydroxyandrogen. It is suggested
      that the mechanistic kinship between hydroxylation and olefin formation, revealed
      by the present study, also applies to conventional hydroxylation and desaturation
      reactions.

PMID- 7578008
TI  - Analysis of the kinetic mechanism of enterococcal NADH peroxidase reveals
      catalytic roles for NADH complexes with both oxidized and two-electron-reduced
      enzyme forms.
AB  - Anaerobic titrations of the two-electron-reduced NADH peroxidase (EH2) with NADH
      and 3-acetylpyridine adenine dinucleotide (AcPyADH) yield the respective
      complexes without significant formation of the four-electron-reduced enzyme
      (EH4). Further analysis of the EH2/EH4 redox couple, however, yields a midpoint
      potential of -312 mV for the free enzyme at pH 7. The catalytic mechanism of the
      peroxidase has been evaluated with a combination of kinetic and spectroscopic
      approaches, including initial velocity and enzyme-monitored turnover
      measurements, anaerobic stopped-flow studies of the reactions of both oxidized
      enzyme (E) and EH2 with NADH and AcPyADH, and diode-array spectral analyses of
      both the reduction of E-->EH2 by NADH and the formation of EH2.NADH. Overall,
      these results are consistent with rapid formation of an E.NADH complex with
      distinct spectral properties and a rate-limiting hydride transfer step that
      yields EH2, with no direct evidence for intermediate FADH2 formation. The
      EH2.NADH complex described previously [Poole, L. B., & Claiborne, A. (1986) J.
      Biol. Chem. 261, 14525-14533] is not catalytically competent and reacts
      relatively slowly with H2O2. Stopped-flow analyses do, however, support the very
      rapid formation of an EH2.NADH* intermediate, with spectral properties that
      distinguish it from the static EH2.NADH form, and yield a first-order rate
      constant for the conversion between the two species that is smaller than kcat.
      The combined rapid-reaction and steady-state data are best accommodated by a
      limiting type of ternary complex mechanism very similar to that proposed
      previously [Parsonage, D., Miller, H., Ross, R.P., & Claiborne, A. (1993) J.
      Biol. Chem. 268, 3161-3167].

PMID- 7578010
TI  - Influence of the extent of branching on solution conformations of complex
      oligosaccharides: a molecular dynamics and NMR study of a penta-antennary
      "bisected" N-glycan.
AB  - The solution conformation of an agalactosyl penta-antennary "bisected" N-linked
      glycan from hen ovomucoid has been determined using a combination of 1H-NMR NOE
      measurements and restrained molecular dynamics (MD) simulations. The majority of
      glycosidic linkages exhibited restricted torsional fluctuations about the global
      minimum energy configuration, of an extent which was generally less than that
      observed in N-linked glycans with a smaller number of antennae. The locations of
      terminal galactose residues in the native glycan, which exhibit branch
      specificity, could not readily be rationalized in terms of relative accessibility
      by the relevant galactosyltransferase of the various nonreducing terminal 2
      acetamido-2-deoxy-D-glucopyranose (GlcNAc) residues in the agalactosyl glycan,
      suggesting either that the parent protein exhibits substantial control over
      glycosylation or that more than one transferase is responsible for
      galactosylation.

PMID- 7578009
TI  - Structural and electronic similarity but functional difference in methylmalonyl
      CoA mutase between coenzyme B12 and the analog 2',5'-dideoxyadenosylcobalamin.
AB  - The cofactor analog 2',5'-dideoxyadenosylcobalamin (ddAdoCbl) differs from the
      natural cofactor coenzyme B12 [5'-deoxyadenosylcobalamin (dAdoCbl)] by lacking
      only one oxygen atom. The 1H and 13C NMR spectra of ddAdoCbl have been assigned
      unambiguously by homonuclear and heteronuclear 2D NMR techniques. The 1H, 13C,
      and 31P chemical shift values for ddAdoCbl were compared with those of another
      organocobalamin, namely dAdoCbl. This assessment shows that the analog is very
      similar both electronically and structurally to the natural cofactor. The
      effectiveness of ddAdoCbl as a cofactor for both the human and Propionibacterium
      shermanii methylmalonyl-CoA mutases was compared with that of the natural
      cofactor. ddAdoCbl was found to be a competitive inhibitor with respect to
      dAdoCbl. Similar binding affinities to both enzymes were found for both the
      ddAdoCbl analog and the natural cofactor. However, in the presence of ddAdoCbl,
      the rate of conversion of methylmalonyl-CoA to succinyl-CoA was only 1-2% of that
      seen with the natural cofactor. There were no changes with time in the visible
      absorption spectrum of the bound cofactor analog in the presence of substrate,
      suggesting that the Co-C bond was not cleaved. The CD (circular dichroism)
      spectra of dAdoCbl and ddAdoCbl are very similar, consistent with the NMR
      results. The CD spectral changes upon binding to P. shermanii methylmalonyl-CoA
      mutase are large compared to those reported on the binding of dAdoCbl to
      ethanolamine ammonia lyase. Furthermore, the CD spectra of both enzyme-bound
      cobalamins are very similar, suggesting that similar changes in the conformation
      or structure in these cobalamins occur on binding to the enzyme.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578011
TI  - Tryptophan dynamics and structural refinement in a lipid bilayer environment:
      solid state NMR of the gramicidin channel.
AB  - Tryptophans in the gramicidin channel are important for defining the conformation
      and the orientation with respect to the bilayer normal and for facilitating
      cation conductance. Here, high-resolution structure and dynamics of these rings
      are characterized by solid state NMR. Both oriented and unoriented lipid bilayer
      preparations are used. Fast frozen lipid bilayer preparations of unoriented
      samples have been used to obtain static characterizations of nuclear spin
      interaction tensors. The temperature dependence of these unoriented samples and
      the spectral features of fast frozen oriented samples were used to experimentally
      define the local motions of the individual indole rings. Local motions were shown
      to have amplitudes as high as +/- 29 degrees, and the motions were dominated by
      libration about the chi 2 axis. The high-resolution structure has been achieved
      by interpreting seven precise (+/- 0.3 degree) orientational constraints from 2H
      and 15N NMR for each indole ring in light of the motionally averaged interaction
      tensors. Each of the four indoles is restricted to a unique orientation of the
      ring with respect to the bilayer normal and one of two possible rotameric states.
      The side chain torsion angles for each residue are very similar, generating
      similar electric dipole moment orientations with respect to the channel.

PMID- 7578012
TI  - Tryptophan hydrogen bonding and electric dipole moments: functional roles in the
      gramicidin channel and implications for membrane proteins.
AB  - The known high-resolution structure and dynamics characterization of the lipid
      bilayer-bound polypeptide gramicidin A provides a unique opportunity to study
      structure-function and dynamics-function correlations in a model membrane
      protein. In particular, the indoles have a variety of very important functional
      roles in this cation channel that will undoubtedly be recognized in membrane
      proteins. That indoles and phenols are oriented at the hydrophobic-hydrophilic
      interface of lipid bilayers is already well-recognized in membrane proteins. The
      most buried indole of the gramicidin channel, Trp9, is shown by 15N solid state
      NMR to be exposed to the hydrophilic surface through hydrogen exchange. Here the
      importance of the indole dipole moments is described for cation conductance.
      Preparation of samples with high concentrations of Na+ is shown by high
      resolution orientational constraints derived from 2H NMR to have no structural
      effect on the indole side chain conformations. These dipoles stabilize cations in
      the binding sites near the channel entrance and substantially reduce the
      potential energy barrier at the bilayer center. This latter finding conclusively
      documents that the rate-limiting step in cation conductance by this channel
      involves the barrier at the bilayer center. Furthermore, dynamics of the indole
      rings cause significant fluctuations in the energy of stabilization at the
      binding site that may result in a rapid mechanism for gating the channel.

PMID- 7578013
TI  - Bacterial expression of the linker region of human MDR1 P-glycoprotein and
      mutational analysis of phosphorylation sites.
AB  - Phosphorylation may play a role in modulating multidrug resistance by P
      glycoprotein (P-gp). The linker region between the two homologous halves of human
      P-gp harbors several serine residues which are phosphorylated by protein kinase C
      (PKC) in vitro. We used the glutathione S-transferase gene fusion system to
      express and purify a series of fusion proteins containing the relevant portion
      (residues 644-689) of the linker region of the human MDR1 gene product. The
      fusion proteins were subjected to in vitro phosphorylation and phosphopeptide
      mapping analysis to identify specific phosphorylation sites. On the basis of a
      mutational strategy in which individual serine residues were systematically
      replaced with nonphosphorylatable alanine residues, Ser-661 and Ser-667 were
      identified as major PKC sites and Ser-683 was identified as a minor PKC site. Ser
      661 and Ser-667 were also found to be the primary sites of phosphorylation for a
      novel membrane-associated P-gp specific kinase isolated from the multidrug
      resistant KB-V1 cell line. Individual phosphorylation sites were recognized
      independently of each other. These data show that the linker region of P-gp
      represents a target for multisite phosphorylation not only for PKC but also for
      the P-gp specific V1 kinase. Specific serine phosphorylation sites are
      identified, and evidence is presented that the V1 kinase has a specificity which
      overlaps, but is more restricted than, that of PKC. In addition, these studies
      also suggest that the use of GST fusion peptides may be applicable for the
      analysis of multisite and ordered protein phosphorylation in other systems.

PMID- 7578014
TI  - Cysteines 638 and 665 in the hormone binding domain of human glucocorticoid
      receptor define the specificity to glucocorticoids.
AB  - To understand the function of cysteines, we have substituted cysteines 638, 643,
      and 665 by serine in the hormone-binding domain (HBD) of the human glucocorticoid
      receptor (hGR). In hormone-binding assays using [3H]dexamethasone, hGR C643S and
      hGR C665S exhibited wild type receptor Kd of 2.5 nM and hGR C665SM666L displayed
      a Kd of 3.7 nM, while hGR C638S exhibited a Kd of 162 pM, a 15-fold higher
      affinity. The affinity of hGR C638S for RU486 was 10-fold higher, and the mutants
      C643S and C665S bound RU486 with a 10-fold lower affinity when compared to wild
      type GR. While C665S bound aldosterone with very high relative affinity, the
      double mutant C665SM666L failed to bind aldosterone. The expression of wild type,
      mutant, and truncated hGRs in vitro showed an identical level of expression of
      the cloned receptors. Similar levels of expression of the receptors were observed
      in transfected cells, both by immunoprecipitation and by Western blotting.
      Transcription activation of the chimeric reporter gene mouse mammary tumor virus
      chloramphenicol acetyltransferase (MMTV-CAT) with hGR C638S was 4-fold higher
      than the level observed with wild type hGR in the presence of dexamethasone. In
      the presence of RU486, hGR C638S induced MMTV-CAT 25-fold compared to the highest
      levels observed with wild type hGR and RU486. Even though the hGR C665S
      stimulated transcription with aldosterone, hGR C665SM666L did not. DNA-receptor
      interaction analyses by gel mobility shift assay demonstrated that the increased
      transactivation potential of hGR C638S was due to its intense interaction with
      DNA. These findings suggest that C638 and C665 are involved in maintaining
      specificity to glucocorticoids.

PMID- 7578015
TI  - A multinuclear solid-state NMR study of phospholipid-cholesterol interactions.
      Dipalmitoylphosphatidylcholine-cholesterol binary system.
AB  - Multinuclear (1H, 13C, 31P) MASNMR and static solid-state 31P NMR were used to
      study the molecular interactions between dipalmitoylphosphatidylcholine (DPPC)
      and free cholesterol (CHOL) in multilayers of DPPC containing 0-65 mol % CHOL
      with respect to total lipid at temperatures between 25 and 55 degrees C. 13C
      chemical shifts and line shapes for DPPC and CHOL resonances were measured in 13C
      MASNMR spectra. The apparent chemical shift anisotropy (CSA) of the DPPC acyl
      methylene resonances [(CH2)n] was calculated from the 1H MASNMR spectra. CSA and
      line shape changes were recorded as a function of CHOL content by 31P static
      solids and MASNMR. The presence of CHOL significantly changed the 13C chemical
      shifts and line shapes of DPPC carbonyl carbons below or above the main
      transition temperature of pure DPPC. Chemical shift changes were also observed
      for CHOL carbons as a function of the mixing ratio, signifying a changing local
      environment of CHOL. For mixtures with CHOL > 50 mol %, 13C MASNMR detected
      crystalline CHOL in the monohydrate form. When the excess CHOL was in a
      submicroscopic crystalline form that was not readily detected by differential
      scanning calorimetry, or optical microscopy (but readily observed by 13C MASNMR),
      the 31P powder pattern was affected, suggesting interaction of the excess CHOL
      with the aqueous interface of the bilayer. These results suggest the potential of
      13C MASNMR for detection of crystalline CHOL in biological samples.

PMID- 7578016
TI  - Candidate gamma-secretases in the generation of the carboxyl terminus of the
      Alzheimer's disease beta A4 amyloid: possible involvement of cathepsin D.
AB  - beta A4 amyloid peptide, the main constituent of amyloid plaques and
      cerebrovascular amyloid deposits associated with Alzheimer's disease, derives
      from a large precursor protein (APP) by the action of beta- and gamma-secretases,
      the unidentified endoproteases which release the amino and carboxyl termini of
      beta A4, respectively. Several gamma-secretase cleavage sites exist which yield
      the more soluble (1-39/40) forms of beta A4 and the longer forms (1-42/43) which
      have a greater tendency to aggregate into amyloid plaques. gamma-Secretase
      activity may therefore be critical in amyloid formation. In this study, a
      synthetic peptide which encompasses the various gamma-secretase cleavage sites
      was used as a substrate to probe proteases of various classes and specificities.
      Elastase, collagenase, and cathepsin D cleaved at the amyloidogenic sites (after
      Ala42 or after Thr43) to release the carboxyl termini of the aggregating forms.
      In addition, collagenase and pepsin released the carboxyl terminus of the more
      soluble forms. Human brain fractions enriched in lysosomes contained a
      proteolytic activity that cleaved the substrate at the amyloidogenic site(s).
      This activity was more active at acidic pH and was inhibited by pepstatin, two
      characteristics of the lysosomal aspartyl proteinase cathepsin D. The same
      lysosomal fractions were found to contain APP carboxyl-terminal fragments which
      are potentially amyloidogenic. These were degraded, only in acidic conditions, by
      an endogenous protease activity inhibited by pepstatin. Thus, a cathepsin D-like
      activity from human brain is a candidate for APP gamma-secretase(s).

PMID- 7578017
TI  - Regulation of human interleukin-8 receptor A: identification of a phosphorylation
      site involved in modulating receptor functions.
AB  - The human type A interleukin-8 receptor (IL-8RA) was modified to express an amino
      terminal epitope tag and stably overexpressed in a rat basophilic leukemia cell
      line (RBL-2H3). This receptor (ET-IL-8RA) displayed functional properties similar
      to those of the native receptor in neutrophils in that exposure to IL-8
      stimulated GTPase activity, phosphoinositide (PI) hydrolysis, intracellular
      calcium mobilization, and degranulation in a pertussis toxin (PTx) susceptible
      fashion. IL-8 induced dose- and time-dependent phosphorylation of ET-IL-8RA.
      Phorbol 12-myristate 13-acetate (PMA) treatment also resulted in phosphorylation
      of the receptor although to a lesser extent. Staurosporine totally blocked PMA
      induced phosphorylation but only partially inhibited IL-8-mediated
      phosphorylation. Phosphorylation of ET-IL-8RA correlated with its desensitization
      as measured by GTPase activation and calcium mobilization. To determine the role
      of phosphorylation in IL-8RA signal transduction, three mutants lacking specific
      serine and threonine residues located at the C-terminal of this receptor were
      constructed by site-directed mutagenesis (M1, M2, and M3). The mutated receptors
      expressed in RBL-2H3 cells displayed pharmacological properties (Kd approximately
      2-2.8 nM and Bmax approximately 3-3.5 pmol/mg of protein) similar to those of the
      wild-type ET-IL-8RA. M2 and M3, but not M1, showed a marked decrease in IL-8
      induced phosphorylation compared to the wild-type receptor. M2 and M3 but not M1
      were resistant to PMA-mediated phosphorylation and desensitization and were also
      more resistant to homologous desensitization than M1 or ET-IL-8RA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578018
TI  - Liposome fusion induced by a M(r) 18,000 protein localized to the acrosomal
      region of acrosome-reacted abalone spermatozoa.
AB  - A M(r) 18,000 protein is secreted by abalone spermatozoa during the acrosome
      reaction. Immunofluorescence of acrosome-reacted sperm localizes the protein as a
      coating on the spent acrosomal granule hull and on the surface of the acrosomal
      process. The membrane of the acrosomal process fuses with the egg plasma membrane
      at fertilization. The M(r) 18,000 acrosomal protein aggregates negatively charged
      (but not neutral) large unilamellar liposomes and renders them permeable to
      internal probe. The M(r) 18,000 proteins from two abalone species are potent
      inducers of intervesicular lipid mixing in the resonance energy transfer assay,
      suggesting that they mediate the fusion of lipid bilayers. Predicted secondary
      structures of these proteins show the presence of strongly amphipathic alpha
      helices that may be active in the perturbation of phospholipid bilayers. The M(r)
      18,000 protein may mediate sperm-egg fusion during fertilization.

PMID- 7578019
TI  - The nature of the thermal equilibrium affecting the iron coordination of ferric
      cytochrome c.
AB  - In cytochrome c, ligation of the heme iron by the methionine-80 sulfur plays a
      major role in determining the structure and the thermodynamic stability of the
      protein. In the ferric state, this bond is reversibly broken by moderately acid
      or alkaline pH's (pK's 2.5 and 9.4, respectively) and by exogenous ligands. NMR
      studies of horse ferricytochrome c in which the Met-65 and Met-80 methyl groups
      were chemically enriched with 13C demonstrate that, at 59 degrees C, a
      temperature at which the protein is still folded, the sulfur-iron bond is already
      partially broken. This structural change corresponds to the reversible
      disappearance upon moderate heating of the 695 nm band, characteristic of the
      sulfur-iron coordination of this protein. The thermal effect results from a shift
      in the alkaline pK from 9.4 at 25 degrees C to 8.2 at 59 degrees C. The exchange
      rate from iron-bound to free methionine-80 at 59 degrees C is 1.8 s-1, as
      measured by saturation transfer experiments. The free and bound methionine-80
      epsilon-methyl groups in the 1H spectrum are assigned as (1.87, 2.25) and -21.43,
      respectively; in the 13C spectrum they are assigned as 15.6 and 12.8,
      respectively (all these values are in ppm from 3-(trimethylsilyl)propionic
      2,2,3,3-d4 acid, sodium salt).

PMID- 7578020
TI  - Heterologous expression of photoreceptor peripherin/rds and Rom-1 in COS-1 cells:
      assembly, interactions, and localization of multisubunit complexes.
AB  - Peripherin/rds is a 39 kDa integral membrane glycoprotein essential for normal
      photoreceptor cell development in vertebrates. It has been implicated in several
      human retinal degenerative diseases including retinitis pigmentosa and macular
      degeneration and is thought to play a structural role at photoreceptor outer
      segment disk rims, where it forms a tightly-associated complex with rom-1, a
      nonglycosylated 37 kDa homologue. Western blot analysis of COS-1 cells
      transiently transfected with full-length cDNA coding for either peripherin/rds or
      rom-1 indicates that each protein is expressed primarily as a disulfide-linked
      homodimer; recombinant peripherin/rds is glycosylated while recombinant rom-1 is
      not--akin to their counterparts in rod photoreceptor disk membranes. Upon
      cotransfection of the two cDNAs, the specific assembly of a stable peripherin/rds
      -rom-1 complex is observed. Immunofluorescence microscopy studies demonstrate
      that both singly and coexpressed peripherin/rds and rom-1 complexes are localized
      primarily within internal membranes of transfected cells. Velocity sedimentation
      data indicate that the recombinant complexes (4.9 S) are assembled with a subunit
      stoichiometry similar to those extracted from ROS membranes (4.5 S) and are most
      consistent with a tetrameric arrangement of polypeptides. Sedimentation analyses
      of individually expressed peripherin/rds (5.1 S) and rom-1 (4.3 S) suggest that
      each polypeptide can also assemble into a tetrameric form in the absence of its
      homologue partner. Subunit assembly and interactions are discussed in terms of
      their potential role in hereditary retinal diseases.

PMID- 7578021
TI  - FTIR spectroscopy reveals microscopic structural changes of the protein around
      the rhodopsin chromophore upon photoisomerization.
AB  - Fourier transform infrared spectroscopy was used to investigate the local
      structure around the chromophore of rhodopsin and its change upon
      photoisomerization. A hydrated film of bovine rod outer segments was cooled at 80
      K, and difference infrared spectra were obtained between bathorhodopsin and
      rhodopsin or between bathorhodopsin and isorhodopsin under suitable irradiation
      conditions. The spectra in a higher-frequency region (4000-1800 cm-1) revealed
      protein structural change by probing the O-H, N-H, and S-H stretching vibrational
      modes. The structural change of bound water molecules occurred upon formation of
      bathorhodopsin, where three water O-H increased the strength of their H-bonding.
      The water structure is identical in rhodopsin and isorhodopsin. These results
      suggest that the protein in the close proximity of the Schiff base of the
      chromophore is perturbed upon photoisomerization and causes rearrangement of the
      water molecules in bathorhodopsin. Upon the isomerization, the 3463 cm-1 band of
      the 11-cis form (rhodopsin) shifts to 3487 cm-1 for the all-trans form
      (bathorhodopsin) or to 3481 cm-1 for the 9-cis form (isorhodopsin). An N-H bond,
      possibly of an indole of tryptophan residue, is responsible for these bands. It
      is present in a hydrophobic environment around the beta-ionone ring and/or
      polyene chain of the retinal, and changes its geometrical alignment depending on
      the isomeric state. It is the only band distinct in frequency between rhodopsin
      and isorhodopsin in the high-frequency region, suggesting that the specific
      interaction between the N-H and the chromophore contributes to the more efficient
      isomerization in rhodopsin than isorhodopsin. The stretching vibrations of the
      water O-H, cysteine S-H, and amide N-H of the peptide backbone decrease in
      frequency upon formation of bathorhodopsin, indicating that H-bonding around the
      chromophore becomes stronger in bathorhodopsin. This shows that at least a part
      of the energy absorbed in the chromophore is already transferred to the protein
      in bathorhodopsin by strengthened H-bonding. The chromophore-protein interaction
      as a suitable reaction field in rhodopsin is discussed on the basis of these
      observations.

PMID- 7578023
TI  - Role of an N-ethylmaleimide-sensitive factor in the selective cellular uptake of
      low-density lipoprotein free cholesterol.
AB  - Low-density lipoprotein (LDL) was the major contributor to an influx of free
      sterol from plasma which balances high-density lipoprotein (HDL)-mediated efflux
      from cultured skin fibroblasts. When HDL was absent, the uptake of LDL free
      cholesterol was associated with an increase in total cell cholesterol, due in
      part to accumulation of esterified cholesterol. This influx was mediated by a
      high-capacity, low-affinity pathway whose magnitude was similar in normal and LDL
      receptor-deficient cells. In the presence of HDL, some of the interiorized
      labeled LDL free cholesterol became available for HDL-mediated efflux and some
      was interiorized, as a result of a transport mechanism which was sensitive to N
      ethylmaleimide (NEM) and nitrate ion but resistant to progesterone, azide, or
      vanadate. We suggest that normal free cholesterol homeostasis in these cells
      includes the initial binding of LDL followed by the selective transfer of free
      cholesterol to a compartment from which it is either returned to the membrane for
      efflux or internalized for storage or further metabolism within the cell. In the
      presence of NEM, LDL-derived free cholesterol remained mostly accessible for
      efflux from the cell surface. This free cholesterol pathway may function
      physiologically to stabilize plasma membrane cholesterol levels against the
      effect of varying concentrations of HDL and LDL.

PMID- 7578022
TI  - Denaturant unfolding of the ferric enterobactin receptor and ligand-induced
      stabilization studied by site-directed spin labeling.
AB  - FepA is an integral outer membrane protein that is the specific receptor for the
      siderophore, ferric enterobactin, and is thus primarily responsible for iron
      uptake in many Gram-negative bacteria. A site-specific mutant of FepA, containing
      a single introduced cysteine in the ligand-binding domain, was spin labeled and
      used to examine the denaturant-induced unfolding of this receptor with guanidine
      hydrochloride (Gdn-HCl) and urea. Electron spin resonance (ESR) spectra showed
      conversion of the spin label from a motionally-restricted, immobilized
      environment to a freely-accessible, rotationally-mobile state upon denaturation.
      Unfolding was also followed by nondenaturing polyacrylamide gel electrophoresis
      (PAGE), which is sensitive to loss of the putative transmembrane beta-structure,
      and displayed a similar concentration dependence. Unfolding occurred over
      relatively narrow ranges of denaturant concentration, indicating a high degree of
      cooperativity. Unfolding was fully reversible under the conditions employed.
      Rapid, spontaneous refolding occurred in the presence of Triton X-100 and did not
      require exogenous lipids. Refolding could be induced by either dialysis, dilution
      to low denaturant concentration, or ethanol precipitation. At ambient temperature
      the free energy of unfolding extrapolated to zero denaturant concentration (delta
      GU zero) was 6.24 +/- 0.63 kcal/mol. Values of delta GU zero obtained with Gdn
      HCl and urea were in good agreement, as were values obtained from linear
      extrapolation and nonlinear regression fitting to a two-state equilibrium. This
      is the first report of a quantitative evaluation of the free energy of unfolding
      for an integral membrane protein.

PMID- 7578024
TI  - Insights into the catalytic mechanism and active-site environment of Comamonas
      testosteroni delta 5-3-ketosteroid isomerase as revealed by site-directed
      mutagenesis of the catalytic base aspartate-38.
AB  - Delta 5-3-Ketosteroid isomerase (KSI) of Comamonas testosteroni catalyzes the
      isomerization of a wide variety of delta 5(6) and delta 5(10) steroids through
      the formation of an enzyme bound dienol(ate) intermediate. Asp-38 has been
      strongly implicated in catalysis, apparently serving as a proton shuttle. In this
      paper the results of a detailed kinetic characterization of the KSI mutants D38E
      and D38H are presented. Both mutants retain significant activity, with kcat and
      kcat/Km values 10(3)-10(4) times greater than the D38N mutant. The results allow
      for a qualitative assessment of the sensitivity of the enzymes catalytic
      capability to the positioning and chemical nature of the catalytic base. The near
      identity of the ratios of kcat5-AND/kcat5,10-EST is most easily explained by a
      mechanism in which the second chemical step, reketonization of the intermediate
      dienol(ate), is not significantly rate determining. The pH dependence of the rate
      constants for the D38E and D38H mutants is found to be consistent with earlier
      proposals that an as yet unidentified titrating functional group is present in
      the active site and indicates that the electrostatic environment of residue 38 is
      hydrophobic and positively charged.

PMID- 7578025
TI  - Interfacial catalysis by phosphoinositide 3'-hydroxykinase.
AB  - Phosphorylation of phosphoinositides by phosphoinositide 3'-hydroxykinase (PI3K)
      occurs at a lipid/water interface. We have determined that highly purified
      recombinant human P13K binds tightly to vesicle interfaces composed primarily of
      phosphatidylinositol (PI) or 1,2-dimyristoyl-sn-glycero-3-phosphomethanol (DMPM).
      The rate of desorption of PI3K from the vesicle interface is slow and does not
      significantly affect the observed product formation kinetics. Observations which
      demonstrate that PI3K is tightly bound to the vesicle lipid/water interface
      include the following: (1) product formation plateaus rapidly, even in the
      presence of active enzyme and excess substrate; (2) total product formation is
      proportional to the amount of PI3K; (3) initial product formation rates are
      unaffected by bulk lipid concentration but are dependent on the interfacial
      substrate concentration; and (4) PI3K partitions with lipid vesicles in
      sedimentation gradients. This enzymatic profile has been referred to as catalysis
      in the "scooting" mode (Berg et al., 1991). A kinetic analysis of PI3K catalysis
      in the scooting mode is presented. The interfacial Km,app for PI was determined
      to be approximately 6.0 mol % in PI/DMPM vesicles. The ratio of specificity
      constants (kcat/Km) for PI, phosphatidylinositol 4-monophosphate (PIP), and
      phosphatidylinositol 4,5-diphosphate (PIP2) utilization was determined to be near
      unity. These results provide a rigorous enzymological framework for the kinetic
      analysis of PI3K inhibitors.

PMID- 7578026
TI  - On the role of ligand in retinoid signaling: positive cooperativity in the
      interactions of 9-cis retinoic acid with tetramers of the retinoid X receptor.
AB  - Previously, we have shown that the retinoid X receptor (RXR) forms tetramers with
      a high affinity and that interactions of the receptor with its ligand, 9-cis
      retinoic acid (9cRA), result in dissociation of protein tetramers. Here it is
      shown by fluorescence anisotropy studies that ligand-induced tetramer
      dissociation displays a pronounced positive cooperativity. The binding affinity
      of RXR for 9cRA at low saturation levels of the receptor with ligand was found to
      be significantly weaker than the affinity observed at higher levels of
      saturation. In addition, the rate of dissociation of 9cRA from RXR was found to
      be faster at low vs. high saturation levels of the receptor. These data suggest
      that the observed positive cooperativity of the ligand-induced dissociation of
      RXR tetramers stems from positive cooperativity in binding of 9cRA by the
      receptor. Kinetic studies showed that dissociation of RXR tetramers upon ligand
      binding is a rapid reaction characterized by a t1/2 of 80 ms, which is about 5
      orders of magnitude faster than the rate of dissociation in the absence of
      ligand. The data indicate that the oligomeric state of RXR is tightly regulated
      by the precise concentrations of 9cRA and that it rapidly responds to changes in
      the ligand's concentrations. These findings further substantiate the hypothesis
      that modulation of the oligomeric state of RXR by 9cRA is an important regulatory
      step in the pathway by which retinoids affect gene transcription.

PMID- 7578027
TI  - Regulatory mechanism of human factor IX gene: protein binding at the Leyden
      specific region.

PMID- 7578028
TI  - Sulfated disaccharide inhibitors of L-selectin: deriving structural leads from a
      physiological selectin ligand.
AB  - The selectins are a family of three adhesion molecules (L-, P-, and E-) that
      direct the interaction of circulating leukocytes with endothelial cells during
      the first step in recruitment to tissue sites. Their involvement in inflammatory
      disease makes the selectins attractive targets for anti-inflammatory therapy. The
      sialyl Lewis x tetrasaccharide binds weakly to all three selectins and has
      demonstrated anti-inflammatory activity in vivo. However, the synthetic
      difficulties inherent to sialylated and fucosylated oligosaccharides motivate the
      search for alternative antagonists. Here we demonstrate that information gained
      from the biochemical analysis of a physiological selectin ligand can provide new
      leads for small molecule design. Previous structural analysis of the
      oligosaccharide chains on GlyCAM-1, an endothelial-derived ligand for L-selectin,
      revealed two novel structures: 6'-sulfo sialyl Lewis x and 6-sulfo sialyl Lewis
      x. The sulfate esters on these structures are thought to be essential for high
      affinity binding to L-selectin. By incorporating sulfate esters on the analogous
      positions of the disaccharide lactose, we generated a simple small molecule
      (lactose 6',6-disulfate) with greater inhibitory potency for L-selectin than
      sialyl Lewis x.

PMID- 7578029
TI  - A novel calcium-dependent activator of retinal rod outer segment membrane
      guanylate cyclase.
AB  - The membrane guanylate cyclase in retinal rod outer segments (ROS-GC) is known to
      be negatively regulated by calcium; when the calcium concentration is reduced
      below the dark-adapted level of about 500 nM, the enzyme is activated by a
      soluble protein. We now report that the enzyme is also positively regulated by
      calcium; a novel soluble protein is identified and purified from bovine retina
      which activates ROS-GC, with half-maximal activation occurring at 2-5 microM
      calcium. The activation is dose-dependent, and at its maximum, cyclase is
      stimulated up to 25-fold. The activator has a molecular mass of about 40 kDa and
      is a multimer of a 6-7 kDa peptide.

PMID- 7578030
TI  - Folding of an enzyme into an active conformation while bound as peptidyl-tRNA to
      the ribosome.
AB  - Rhodanese bound to bacterial ribosomes as peptidyl-tRNA can be folded into an
      enzymatically active conformation by generating C-terminal extensions of the wild
      type enzyme. Rhodanese was synthesized by coupled transcription/translation in a
      cell-free Escherichia coli system from plasmids containing the coding sequences
      for the wild-type enzyme or its C-terminally extended mutants. Two proteins with
      extensions of 23 amino acids or longer were enzymatically active while bound to
      the ribosomes whereas wild-type protein and a 13-amino acid extension were not.
      All forms of the enzyme were active after termination and release of the full
      length protein from the ribosomes. All five of the bacterial chaperones were
      required to substantially increase the specific enzymatic activity of the
      extended rhodanese while the nascent protein was bound to ribosomes. The results
      provide direct support for the hypothesis that proteins acquire tertiary
      structure as they are formed in ribosomes.

PMID- 7578031
TI  - Plasma membrane caveolae mediate the efflux of cellular free cholesterol.
AB  - Caveolae are clathrin-free cell-surface organelles implicated in transmembrane
      transport. A fibroblast caveolar membrane fraction was isolated by sucrose
      density gradient ultracentrifugation and its identity confirmed by protein
      markers (caveolin, annexin II). When 3H-labeled free cholesterol was selectively
      transferred to the cells from labeled low density lipoprotein to increase cell
      free cholesterol approximately 15%, there was a 6-fold increase in label in the
      caveolar fraction above baseline levels. Subsequent incubation of these cells
      with unlabeled native plasma or plasma high density lipoprotein selectively
      unloaded caveolar free cholesterol into the medium. Okadaic acid, which decreased
      caveolar activity as measured by cholera toxin binding and uptake, decreased
      cholesterol efflux in parallel. Cholesterol newly synthesized from [3H]mevalonate
      was also preferentially incorporated into the caveolar fraction and selectively
      released by plasma into the medium. Together these data indicate that caveolae
      represent a major site of efflux of both newly synthesized and low density
      lipoprotein-derived free cholesterol in these cells.

PMID- 7578032
TI  - Alpha-DNA, a single-stranded secondary structure stabilized by ionic and hydrogen
      bonds: d(A(+)-G)n.
AB  - A novel nucleic acid secondary structure, exemplified by d(A(+)-G)10, is formed
      by an intramolecular, cooperative, acid-induced, coil-->helix transition. The
      helix is apparently left-handed, lacks base stacking and pairing, and is
      maintained by hydrogen and ionic bonds between dA+ "side-chain" residues (with
      electropositive hydrogens -N6H2, -N1+H) and the phosphodiester backbone. Modeling
      indicates that those dA+ residues lie approximately parallel to the helix axis,
      interacting with the n-1 backbone phosphates (with electronegative oxygens),
      somewhat like the -C=O...H-N- longitudinal interactions in a protein alpha-helix.
      Moreover, the intervening dG side-chain residues are extrahelical, as are amino
      acid side chains of an alpha-helix.

PMID- 7578034
TI  - Structures of a series of 6-kDa trypsin inhibitors isolated from the stigma of
      Nicotiana alata.
AB  - The three-dimensional structures of a series of 6-kDa trypsin inhibitors isolated
      from the stigma of the ornamental tobacco Nicotiana alata have been determined by
      1H NMR spectroscopy combined with simulated annealing calculations. The proteins,
      T1-T4, are proteolytically cleaved from a 40.3-kDa precursor protein, NA-proPI,
      together with a chymotrypsin inhibitor, C1, the structure of which was reported
      recently [Nielsen, K.J., Heath, R.L., Anderson, M.A., & Craik, D.J. (1994) J.
      Mol. Biol. 242, 231-243]. Each of the proteinase inhibitors comprises 53 amino
      acids, including 8 cysteine residues which are linked to form 4 disulfide
      bridges. The proteins have a high degree of sequence identity and differ mainly
      in residues around the putative reactive sites. The structure of T1 was
      determined using a set of 533 interproton distance restraints derived from NOESY
      spectra, combined with 33 dihedral restraints derived from 3JNH-H alpha coupling
      constants and 16 hydrogen bonds. The structures of the remaining inhibitors (T2
      T4) were deduced to be almost identical to T1, on the basis of their similar
      chemical shifts and 2D spectra. The current study demonstrates that the
      structures of the trypsin inhibitors (T1-T4) are similar to that previously found
      for the chymotrypsin inhibitor, C1. Despite differences in sequence, there is
      conservation in backbone geometry between the reactive site loops of the two
      classes of inhibitors. From this, it is clear that the nature of the side chain
      on the primary binding residue, rather than the backbone fold, is the main
      determinant of the enzyme specificities of these proteinase inhibitors.

PMID- 7578033
TI  - A UV resonance Raman study of d(A(+)-G)10, a single-stranded helix without
      stacked or paired bases.
AB  - UV resonance Raman spectroscopy has been utilized to directly observe structural
      features of the recently described nucleic acid single-stranded helix d(A(+)
      G)10. An absence of base stacking is confirmed by invariant hypochromic ratios of
      dominant vibrational modes for the oligomer relative to its constituent monomers
      as the structure is thermally denatured. The N1 of dA residues is protonated, as
      determined by similarity to the ring-stretching vibrations for protonated adenine
      and its derivatives. Selective resonance enhancement of Raman vibrational modes
      from dA and dG residues shows frequency shifts upon thermal denaturation that
      confirm the participation of the exocyclic amino of dA but not dG residues in H
      bonding. Conformationally sensitive glycosyl bond modes suggest anti residue
      conformations.

PMID- 7578035
TI  - Site-directed mutagenesis as a tool for molecular modeling of cytochrome P450
      2B1.
AB  - Prompted by our previous homology model of cytochrome P450 2B1 based on the 3-D
      structure of P450cam [Szklarz, G. D., Ornstein, R. L., & Halpert, J. R. (1994) J.
      Biomol. Struct. Dyn. 12, 61-78], we constructed 11 new site-directed mutants at
      positions 100, 111, 205, 209, 291, 477, and 480 and expressed the enzymes in
      Escherichia coli. The mutations at positions 209, 477, and 480 affected
      androstenedione and progesterone hydroxylation as predicted by the model. For
      example, the Ile-477-->Ala and Ile-480-->Ala mutants retained < or = 5% activity
      with androstenedione and progesterone but were active with benzphetamine, whereas
      the Leu-209-->Ala mutant catalyzed 21-hydroxylation of progesterone. Mutations at
      the other positions, i.e., 100, 111, 205, and 291, did not change enzyme
      activity, contrary to predictions. Therefore, an improved molecular model of
      cytochrome P450 2B1 was constructed. An alignment of the P450 2B1 sequence with
      P450 BM-3, P450cam, and P450terp was optimized using data from site-directed
      mutagenesis at 27 positions in various cytochromes P450 2B and docking of
      androstenedione into the active site of the known crystal structures. Because all
      three structures were found to be suitable templates for P450 2B1, the new model
      was formulated on the basis of the crystallographic coordinates of the three
      proteins using a consensus strategy, a modeling method based on distance geometry
      calculations. The new model provides a means to explain alterations in regio- and
      stereospecificity of steroid hydroxylation upon residue substitution at key amino
      acid positions, including positions 114, 206, 209, 290, 302, 363, 367, 477, 478,
      and 480 in P450 2B1.

PMID- 7578036
TI  - 1.7 A structure of FR-1, a fibroblast growth factor-induced member of the aldo
      keto reductase family, complexed with coenzyme and inhibitor.
AB  - Murine FR-1 is a protein that is induced by fibroblast growth factor-1 and,
      therefore, may play a role in the regulation of the cell cycle. Sequence
      comparison indicates that it is a member of the NADPH-dependent aldo-keto
      reductase family. It bears 70% identity to human aldose reductase, an enzyme
      implicated in diabetic complications and a target for drug design. We have
      determined the 1.7 A resolution structure of the FR-1 in a ternary complex with
      NADPH and zopolrestat, a potent aldose reductase inhibitor. FR-1 folds into a
      (beta/alpha)8 barrel with an active site characterized by a preponderance of
      hydrophobic residues residing in a deep oblong cavity at the C-terminal end of
      the beta-barrel. The nicotinamide moiety of the coenzyme sits in the base of the
      cavity. Zopolrestat occupies the active site cavity and makes numerous contacts
      with several hydrophobic residues. The FR-1 ternary complex structure indicates
      that it uses the same general catalytic mechanism as aldose reductase and other
      members of the family whose structures have been determined. The protein exhibits
      reductase activity with DL-glyceraldehyde as a substrate and is strongly
      inhibited by zopolrestat. When compared with the structure of a similar ternary
      complex of aldose reductase, the binding site retains many of the interactions
      with the coenzyme and inhibitor from the conserved residues. Some differences in
      sequence, however, create a larger binding site that contains six more water
      molecules than in the aldose reductase ternary complex structure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578037
TI  - Mechanism of inhibition of human leucocyte elastase by beta-lactams. 2.
      Stability, reactivation kinetics, and products of beta-lactam-derived E-I
      complexes.
AB  - The monocyclic beta-lactams reported by Knight et al. [Knight, W. B., et al.
      (1992) Biochemistry 31, 8160; Chabin, R., et al. (1993) Biochemistry 32, 8970] as
      inhibitors of human leucocyte elastase (HLE) produce stable HLE-inhibitor
      complexes that slowly reactivate with half-lives ranging from less than 1 to 15 h
      at 37 degrees C. The complexes produced between PPE and two C-3 dimethyl
      substituted beta-lactams are less stable than those produced between HLE and
      analogous C-3 diethyl-substituted lactams. The stability of the HLE-I complexes
      is governed primarily by the structure of the substituted urea portion of the
      inhibitors and not by the identity or presence of a leaving group at C-4 of the
      lactam ring. In some cases substitutions on the urea portion of the inhibitors
      yielded complexes that displayed biphasic reactivation kinetics. This suggests
      the presence of at least two different complexes. The stereochemistry of the
      leaving group at C-4 has a small effect on the stability of the final complex
      (1.3-2-fold); therefore, the identity of the final complex is dependent upon the
      initial stereochemistry at that position. The stability of the complexes was
      relatively insensitive to hydroxylamine, which suggests that the acyl-enzymes are
      protected from nucleophilic "rescue". The rate of reactivation of the complex
      derived from L-680,833,[S-R*,S*)]-4-[(1-(((1-(4-
      methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-oxo-4-azetidinyl)ben zeneacetic
      acid, was pH independent, while the L-684,481, (R)-(1-(((1-(4
      methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-azeti din one generated complex
      displayed a pH-dependent reactivation rate. In the latter case, the increase in
      reactivation rate with pH displayed a pKa of 7.2. This is consistent with the
      requirement for base catalysis by the active site histidine to regenerate
      enzymatic activity. Reactivation of the L-680,833-derived complex produced
      different products as a function of pH, suggesting two different pH-dependent
      routes of reactivation. At low pH a route that produced primarily the substituted
      urea is favored, while at higher pH production of two six-membered ring
      diastereomers competes with urea generation. Thus, the apparent pH independence
      of the return of activity is the result of two offsetting pathways. Other
      compounds such as L-670,258, (S)-4-[((((2-naphthylmethyl)amino)carbonyl)-3,3
      diethyl-4-oxo-2- azetidinyl)oxy]benzoic acid, reactivate by these two routes as
      well as by aminolysis by the other urea nitrogen to produce an additional
      regioisomer. The temperature dependence of the reactivation of the complexes
      derived from L-684,481 and L-680,833 suggests different mechanisms.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7578038
TI  - Mechanism of inhibition of human leucocyte elastase by beta-lactams. 3. Use of
      electrospray ionization mass spectrometry and two-dimensional NMR techniques to
      identify beta-lactam-derived E-I complexes.
AB  - A combination of NMR spectroscopy and electrospray ionization mass spectrometry
      (ESI-MS) was used to probe the identity of beta-lactam-derived complexes with
      serine proteases. The carbon and proton NMR chemical shifts of the human
      leucocyte elastase (HLE)-inhibitor complex derived from [4-13C]-L-680,833, [S
      (R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-oxo-4-
      azetidinyl)oxy]benzeneacetic acid, were consistent with an sp3 hybridized carbon.
      The ESI-MS spectrum of the L-680,833-derived HLE-I complex indicated an increase
      of 333 Da over the mass of the free enzyme. The data are consistent with
      acylation of the active site serine, loss of p-hydroxybenzeneacetic acid, and
      formation of a carbinolamine at the carbon deriving from C-4 of the lactam ring.
      The complexes produced from HLE and the diastereomers of L-680,833 display
      identical masses. Since the 4R-isomers produce more stable complexes [Green et
      al. (1995) Biochemistry 34, 14331-14343], these data suggest that these complexes
      differ in their stereochemistry or conformation. The structural model of the HLE
      I complexes derived from the diastereomers predicts that the hydroxyl of the
      carbinolamine derives from a structurally observed water molecule yielding S
      stereochemistry in all cases. In this model, the 4S- and 4R-diastereomers produce
      complexes that differ by the location of the side chain of a phenylalanine
      residue. The mass of HLE was increased by that of L-684,481, (R)-1-(((1-(4
      methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-azetidino ne, which lacks a
      leaving group at C-4 in the complex derived from this compound. L-691,886, [S
      (R*,S*)]-4-[(1-(((1-(4-ethoxyphenyl)butyl)amino)carbonyl)- 3,3-diethyl-4-oxo-2
      azetidinyl)-oxy]benzeneacetic acid, produces two complexes of different mass that
      reactivate with different rates. The mass of the less stable complex is
      consistent with the acyl-enzyme of 2,2-ethyl-3-oxopropanoic acid while the mass
      of the more stable complex is analogous to the carbinolamine observed during L
      680,833 inactivation. Porcine pancreatic elastase (PPE) produces a complex with a
      mass consistent with replacement of the C-4 leaving group by water to produce a
      carbinolamine from L-684,248, [S-(R*,S*)]-4-[(1-(((1-(4
      methylphenyl)butyl)amino)carbonyl)-3,3-dimethy l - 2-oxo-4-azetidinyl)oxy]benzoic
      acid. The C-4 diastereomer, L-684,249, produces two PPE-I complexes with
      different masses. One of these complexes has a mass identical to the mass of the
      complex derived from L-684,248 while the mass of the other complex indicates the
      presence of the entire inhibitor molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7578039
TI  - Human aldose reductase: rate constants for a mechanism including interconversion
      of ternary complexes by recombinant wild-type enzyme.
AB  - We have used transient kinetic data for partial reactions of recombinant human
      aldose reductase and simulations of progress curves for D-xylose reduction with
      NADPH and for xylitol oxidation with NADP+ to estimate rate constants for the
      following mechanism at pH 8.0: E<-->E.NADPH<-->*E.NADPH<-->*E.NADPH.RCHO<-
      >*E.NADP+.RCH2OH <-->*E.NADP+<--> E.NADP+<-->E. The mechanism includes
      kinetically significant conformational changes of the two binary E.nucleotide
      complexes which correspond to the movement of a crystallographically identified
      nucleotide-clamping loop involved in nucleotide exchange. The magnitude of this
      conformational clamping is substantial and results in a 100- and 650-fold
      lowering of the nucleotide dissociation constant in the productive *E.NADPH and
      *E.NADP+ complexes, respectively. The transient reduction of D-xylose displays
      burst kinetics consistent with the conformational change preceding NADP+ release
      (*E.NADP+-->E.NADP+) as the rate-limiting step in the forward direction. The
      maximum burst rate also displays a large deuterium isotope effect (Dkburst = 3.6
      4.1), indicating that hydride transfer contributes significantly to rate
      limitation of the sequence of steps up to and including release of xylitol. In
      the reverse reaction, no burst of NADPH production is observed because the
      hydride transfer step is overall 85% rate-limiting. Even so, the conformational
      change preceding NADPH release (*E.NADPH-->E.NADPH) still contributes 15% to the
      rate limitation for reaction in this direction. The estimated rate constant for
      hydride transfer from NADPH to the aldehyde of D-xylose (130 s-1) is only 5- to
      10-fold lower than the corresponding rate constant determined for NADH-dependent
      carbonyl reduction catalyzed by lactate or liver alcohol dehydrogenase. Hydride
      transfer from alcohol to NADP+ (0.6 s-1), however, is at least 100- to 1000-fold
      slower than NAD(+)-dependent alcohol oxidation mediated by these two enzymes,
      resulting in a bound-state equilibrium constant for aldose reductase which
      greatly favors the forward reaction. The proposed kinetic model provides a basic
      set of rate constants for interpretation of kinetic results obtained with aldose
      reductase mutants generated for the purpose of examining structure-function
      relationships of different components of the native enzyme.

PMID- 7578040
TI  - Human aldose reductase: subtle effects revealed by rapid kinetic studies of the
      C298A mutant enzyme.
AB  - Transient kinetic data for D-xylose reduction with NADPH and NADPD and for
      xylitol oxidation with NADP+ catalyzed by recombinant C298A mutant human aldose
      reductase at pH 8 have been used to obtain estimates for each of the rate
      constants in the complete reaction mechanism as outlined for the wild-type enzyme
      in the preceding paper (Grimshaw et al., 1995a). Analysis of the resulting
      kinetic model shows that the nearly 9-fold increase in Vxylose/Et for C298A
      mutant enzyme relative to wild-type human aldose reductase is due entirely to an
      8.7-fold increase in the rate constant for the conformational change that
      converts the tight (Ki NADP+ = 0.14 microM) binary *E.NADP+ complex to the weak
      (Kd NADP+ = 6.8 microM) E.NADP+ complex from which NADP+ is released. Evaluation
      of the rate expressions derived from the kinetic model for the various steady
      state kinetic parameters reveals that the 37-fold increase in Kxylose seen for
      C298A relative to wild-type aldose reductase is largely due to this same increase
      in the net rate of NADP+ release; the rate constant for xylose binding accounts
      for only a factor of 5.5. A similar 17-fold increase in the rate constant for the
      conformational change preceding NADPH release does not, however, result in any
      increase in Vxylitol/Et, because hydride transfer is largely rate-limiting for
      reaction in this direction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578041
TI  - Human aldose reductase: pK of tyrosine 48 reveals the preferred ionization state
      for catalysis and inhibition.
AB  - Detailed analyses of the pH variation of kinetic parameters for the forward
      aldehyde reduction and reverse alcohol oxidation reactions mediated by
      recombinant human aldose reductase, for inhibitor binding, and for kinetic
      isotope effects on aldehyde reduction have revealed that the pK value for the
      active site acid-base catalyst group Tyr48 is quite sensitive to the oxidation
      state of the bound nucleotide (NADPH or NADP+) and to the presence or absence of
      the Cys298 sulfhydryl moiety. Thus, the Tyr48 residue of C298A mutant enzyme
      displays a pK value that ranges from 7.6 in the productive *E.NADP+ complex that
      binds and reacts with alcohols to 8.7 in the productive *E.NADPH complex that
      binds and reacts with aldehyde substrates. For wild-type enzyme, Tyr48 in the
      latter complex displays a lower pK value of about 8.25. Assignment of the pK
      values was facilitated by the recognition and quantitation of the degree of
      stickiness of several aldehyde substrates in the forward reaction. The unusual pH
      dependence for Valdehyde/Et and DValdehyde, which decrease roughly 20-fold
      through a wave and remain constant at high pH, respectively, is shown to arise
      from the pH-dependent decrease in the net rate of NADP+ release. The results
      described are fully consistent with the chemical mechanism for aldose reductase
      catalysis proposed previously (Bohren et al., 1994) and, furthermore, establish
      that binding of the spirohydantoin class of aldose reductase inhibitors, e.g.,
      sorbinil, occurs via a reverse protonation scheme in which the ionized inhibitor
      binds preferentially to the *E.NADP+ complex with Tyr48 present as the protonated
      hydroxyl form. The latter finding allows us to propose a unified model for high
      affinity aldose reductase inhibitor binding that focuses on the transition state
      like nature of the *E-Tyr48-OH.NADP+.inhibitor- complex.

PMID- 7578042
TI  - Interactions of dihydroxybenzenes with the Ca(2+)-ATPase: separate binding sites
      for dihydroxybenzenes and sesquiterpene lactones.
AB  - The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is inhibited by 2,5
      di-tert-butyl-1,4-dihydroxybenzene (BHQ) and other hydrophobic 1,4
      dihydroxybenzenes. Inhibitory potency increases on increasing substituent chain
      length from 2,5-dipropyl-1,4-dihydroxybenzene to 2,5-di-tert-amyl-1,4
      dihydroxybenzene, the most potent inhibitor, but then decreases for 2,5-bis(7
      methylheptyl)-1,4-dihydroxybenzene. Kinetic measurements are consistent with
      isomerization following the initial binding of BHQ to the ATPase to give a
      modified E2 conformation, E2AI, as for the binding of sesquiterpene lactones,
      such as thapsigargin. Binding of BHQ to the ATPase shifts the E1-E2 equilibrium
      toward E2 because of the formation of E2AI. Measurements of Ca2+ binding as a
      function of BHQ concentration suggest that BHQ can bind to the E1 conformation of
      the ATPase (but without the subsequent conformational change observed on binding
      to E2) and that the binding constants of E1 for Ca2+ are unaffected by binding of
      BHQ. Binding of BHQ to the ATPase in the presence of substoichiometric amounts of
      thapsivillosin A and effects of mixtures of BHQ and thapsivillosin A show that
      these two inhibitors have separate binding sites on the ATPase.

PMID- 7578043
TI  - Thermodynamic and activation parameters for binding of a pyrene-labeled substrate
      by the Tetrahymena ribozyme: docking is not diffusion-controlled and is driven by
      a favorable entropy change.
AB  - Association and dissociation rates for the pyrene-(pyr)-labeled
      oligoribonucleotide substrate pyrCUCU binding to the L-21 ScaI group I ribozyme
      are reported as a function of temperature. Combined with thermodynamic parameters
      for binding of pyrCUCU to rGGAGAA, the results allow calculation of the
      activation and thermodynamic parameters for docking of pyrCUCU into the catalytic
      core of the ribozyme. The activation enthalpy for docking is 22 kcal/mol, much
      larger than the approximately 4 kcal/mol expected for a diffusion-controlled
      process. Thus, docking is not diffusion-controlled. The activation and
      equilibrium entropies for docking are favorable at 21 and 37 eu, respectively.
      The results suggest the rate-limiting step and the driving force for docking may
      involve desolvation of RNA functional groups or of Mg2+ ions.

PMID- 7578044
TI  - The B form to Z form transition of poly(dG-m5dC) is sensitive to neutral solutes
      through an osmotic stress.
AB  - Several neutral solutes, ranging in size from methanol to a tetrasaccharide,
      stachyose, are shown to stabilize the left-handed Z form of the methylated
      polynucleotide poly(dG-m5dC). The action of these solutes is consistent with an
      osmotic stress, that is, with their effect on water chemical potentials coupled
      to a difference in the number of associated water molecules between the B and Z
      conformations. The apparent difference in hydration between the two forms is,
      however, dependent on the particular solute used to probe the reaction. The
      effect of solutes is not consistent either with a direct binding of solute or
      with an indirect effect on electrostatics or ion binding through changes in the
      solution dielectric constant. The interplay of NaCl and neutral solute in
      modulating the B-Z transition suggests that salt also could be stabilizing the Z
      form through an osmotic stress.

PMID- 7578045
TI  - Divalent zinc cations induce the formation of two distinct homoduplexes of a
      d(GA)20 DNA sequence.
AB  - Homopurine DNA sequences are highly structurally polymorphic. In particular,
      d(GA)n DNA sequences are known to be capable of forming intramolecular foldbacks,
      bimolecular homoduplexes, and tetrastranded complexes. Counterions play a
      determinant role on the equilibria between the different structural conformers of
      d(GA)n sequences. In this paper, the effect of divalent zinc cations on the
      structure of a d(GA)20 oligonucleotide has been analyzed by CD spectroscopy and
      polyacrylamide gel electrophoresis. Depending on the precise experimental
      conditions at which zinc is added, two distinct conformations of the d(GA)20
      oligonucleotide are stabilized. At neutral pH in the absence of zinc, d(GA)20 is
      partially organized into intramolecular foldbacks and bimolecular homoduplexes
      [Casasnovas et al. (1993) J. Mol. Biol. 233, 671-681]. Under these conditions,
      addition of zinc results in the stabilization of the bimolecular homoduplex which
      is nonspecific for zinc since it is also stabilized by divalent magnesium
      cations, increasing ionic strength, or decreasing pH. Its CD spectrum is
      identical to that reported earlier for parallel-stranded d(GA)n homoduplexes
      [Rippe et al. (1992) EMBO J. 11, 3777-3786]. On the other hand, if zinc is added
      under conditions where the d(GA)20 oligonucleotide is exclusively single
      stranded, a different bimolecular homoduplex appears which is only observed in
      the presence of zinc. The zinc-specific duplex melts cooperatively, and, in
      contrast to the nonspecific duplex, its thermostability is high. Transition from
      the nonspecific to the zinc-specific duplex is observed at high zinc
      concentrations or at high temperatures. The transition is cooperative. These
      results are discussed in the context of the specific cation effects on the
      formation of intramolecular R.R.Y triplexes at d(GA.TC)n DNA sequences.

PMID- 7578046
TI  - Solution structure of the CUUG hairpin loop: a novel RNA tetraloop motif.
AB  - The solution structure of a uniformly 13C/15N-labeled CUUG RNA hairpin loop has
      been determined by multidimensional heteronuclear magnetic resonance spectroscopy
      in combination with distance geometry and restrained molecular dynamics
      calculations. The structure of this CUUG tetraloop represents a novel RNA loop
      motif where the first and last loop nucleotides form a standard Watson-Crick C-G
      base pair and the second loop nucleotide interacts directly with the closing base
      pair of the stem by folding into the minor groove. This structure helps explain
      why the closing base pair is phylogenetically conserved and indicates a six
      nucleotide G(CUNG)C motif for the CUUG RNA tetraloop. Implications for the
      function of this CUUG tetraloop in ribosomal RNA and in RNA tertiary interactions
      are discussed.

PMID- 7578047
TI  - Iron release from recombinant N-lobe and mutants of human transferrin.
AB  - Mutations of kinetically active residues in the recombinant N-lobe of human
      transferrin may accelerate or retard release of iron from the protein to
      pyrophosphate, thereby providing means for exploring the individual roles of such
      residues in the concerted mechanisms of release. Using an established
      spectrofluorometric method and pyrophosphate as the required iron-sequestering
      agent, we have compared release from unaltered native transferrin and recombinant
      N-lobe half-transferrin to release from six N-lobe mutants, R124S, R124K, K206R,
      H207E, H249Y, and Y95H. Mutation of R124, which serves as a principal anchor for
      the synergistic carbonate anion ordinarily required for iron binding by
      transferrin, accelerates release. This effect is most marked at endosomal pH,
      5.6, and is also evident at extracellular pH, 7.4, pointing to a critical and
      perhaps initiating role of carbonate in the release process. Mutation of K206 to
      arginine, or of H207 to glutamine, each lying in the interdomain cleft of the N
      lobe, gives products mimicking the arrangements in lactoferrin. Release of iron
      from these two mutants, as from lactoferrin, is substantially slower than from
      unaltered recombinant N-lobe. Interdomain residues not directly involved in iron
      or anion binding may therefore participate in the control of iron release within
      the endosome. The H249Y mutant releases iron much more rapidly than its wild-type
      parent or any other mutant, possibly because of steric effects of the additional
      phenolic ring in the binding site. No simple explanation is available to account
      for a stabilizing effect of the Y95H mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578048
TI  - Divalent metal ions and the internal equilibrium of the hammerhead ribozyme.
AB  - Thermodynamics of RNA cleavage/ligation were measured for a self-cleaving
      hammerhead ribozyme in the presence of Ca2+, Co2+, Mg2+, and Mn2+. The internal
      equilibrium, the ratio of cleaved to ligated RNA, decreases with increasing
      concentrations of each of the four divalent metal ions in a hyperbolic dependence
      that shows saturation. The metal ion dependence is not due to changes in ionic
      strength, and the value of the equilibrium constant at saturation is different
      for each metal ion. The concentration required to achieve half-saturation of the
      equilibrium is also different for each metal ion, and the order of apparent metal
      ion dissociation constants correlates with those measured for dissociation of the
      same metal ions complexed with tRNA and nucleotides. We interpret the divalent
      metal ion dependence of the equilibrium in terms of a thermodynamic model
      invoking noncooperative metal ion dissociation from the cleaved RNA. Thus, at 10
      mM Mg2+, a commonly employed condition for hammerhead kinetic studies, metal ion
      dissociation contributes substantially to the free energy of the equilibrium and
      drives the hammerhead reaction toward cleaved RNA. Temperature dependencies of
      the equilibrium reveal that while the entropy and enthalpy changes of the
      equilibrium depend on the identity of the divalent metal ion, in each case a
      large entropic driving force overcomes an unfavorable change in enthalpy. This
      agrees with thermodynamics previously measured for an intermolecular hammerhead
      in the presence of Mg2+ [Hertel, K. J., & Uhlenbeck, O. C. (1995) Biochemistry
      34, 1744-1749].

PMID- 7578049
TI  - Heparinase I from Flavobacterium heparinum: the role of the cysteine residue in
      catalysis as probed by chemical modification and site-directed mutagenesis.
AB  - Heparinase I (heparin lyase I, EC 4.2.2.7), a heparin-degrading enzyme produced
      by Flavobacterium heparinum, is used to deheparinize blood following
      extracorporeal procedures in surgery and in other applications. The present study
      of mapping and characterization of the cysteines of heparinase I represents the
      first structural characterization of a heparinase. [3H]Iodoacetic acid labeling
      demonstrated that heparinase I has two free cysteines. One of the two cysteines
      is surface accessible and lies in a hydrophilic environment while the other is in
      a hydrophobic environment. Chemical modification of the cysteines, both in the
      presence and in the absence of heparin, suggests that the surface-accessible
      cysteine lies in or near the active site of heparinase I. Preferential reactivity
      of this cysteine with negatively charged sulfhydryl-modifying reagents and the
      cysteines' high reactivity to iodoacetic acid at pH 6.5 indicate that the surface
      accessible cysteine is in a positively charged region. The surface-accessible
      cysteine (cysteine-135) was mapped as the active-site cysteine by radiolabeling
      with [3H]iodoacetic acid and by tryptic digestion and peptide sequencing. Site
      directed mutagenesis of cysteine-135 to a serine or an alanine in r-heparinase I
      demonstrates that this cysteine is essential for enzymatic activity. However,
      replacement of the surface-inaccessible cysteine by a serine or alanine has no
      effect.

PMID- 7578050
TI  - Bent domain structure of recombinant human IgE-Fc in solution by X-ray and
      neutron scattering in conjunction with an automated curve fitting procedure.
AB  - Human immunoglobulin E (IgE) consists of 14 domains, each with the characteristic
      immunoglobulin fold structure. Compared with the 12-domain structure of
      immunoglobulin G (IgG), IgE has an additional pair of domains (C epsilon 2) in
      the Fc region in place of the hinge of IgG. The crystal structure of the 4-domain
      Fc fragment of IgG is known, but not that of the 6-domain Fc fragment of IgE (IgE
      Fc). In order to elucidate the position of the C epsilon 2 domains in the domain
      structure of IgE-Fc, IgE-Fc was studied by synchrotron X-ray and pulsed neutron
      scattering. The upper limit on the X-ray radius of gyration RG which determines
      macromolecular elongation was determined to be 3.52 +/- 0.14 nm. That for the
      neutron RG (measured in 100% 2H2O buffers) was 3.53 +/- 0.05 nm. The X-ray and
      neutron cross-sectional radii of gyration were 1.89 +/- 0.05 and 1.56 +/- 0.09
      nm, respectively. The scattering curves were modeled on the basis of a previously
      predicted model for IgE-Fc (Helm, B. A., Ling, Y., Teale, C., Padlan, E. A., &
      Bruggemann, M. (1991) Eur. J. Immunol. 21, 1543-1548). The extended arrangement
      of domains in that model resulted in poor agreement with experimental data.
      Interactive and automated procedures for the fitting of crystallographically
      derived domain models to scattering data were developed. Each pair of C epsilon
      2, C epsilon 3, and C epsilon 4 domains was translated and rotated relative to
      the remaining structure in a comprehensive five-parameter search of more than
      37,000 models. Substantially improved agreement between the experimental and
      calculated scattering curves was obtained. Bent models for IgE-Fc in which the C
      epsilon 2 domain pair is rotated by at least 40-50 degrees from its position in
      the previously predicted linear IgE model consistently gave the best agreement
      with the X-ray and neutron scattering curves. Such a structure for the Fc
      fragment accounts in part for the bent structure previously proposed for intact
      human IgE, which is important for understanding the interaction between IgE and
      its receptors.

PMID- 7578051
TI  - 1H and 15N NMR sequential assignment, secondary structure, and tertiary fold of
      [2Fe-2S] ferredoxin from Synechocystis sp. PCC 6803.
AB  - The [2Fe-2S] ferredoxin extracted from Synechocystis sp. PCC 6803 was studied by
      1H and 15N nuclear magnetic resonance. Sequence-specific 1H and 15N assignment of
      amino acid residues far from the paramagnetic cluster (distance higher than 8 A)
      was performed. Interresidue NOE constraints have allowed the identification of
      several secondary structure elements: one beta sheet composed of four beta
      strands, one alpha helix, and two alpha helix turns. The analysis of interresidue
      NOEs suggests the existence of a disulfide bridge between the cysteine residues
      18 and 85. Such a disulfide bridge has never been observed in plant-type
      ferredoxins. Structure modeling using the X-PLOR program was performed with or
      without assuming the existence of a disulfide bridge. As a result, two structure
      families were obtained with rms deviations of 2.2 A. Due to the lack of NOE
      connectivities resulting from the paramagnetic effect from the [2Fe-2S] cluster,
      the structures were not well resolved in the region surrounding the [2Fe-2S]
      cluster, at both extremities of the alpha helix and the C and N terminus
      segments. In contrast, when taken separately, the beta sheet and the alpha helix
      were well defined. This work is the first report of a structure model of a plant
      type [2Fe-2S] Fd in solution.

PMID- 7578052
TI  - Three-dimensional structure of the second cysteine-rich repeat from the human low
      density lipoprotein receptor.
AB  - The ligand-binding domain of the low-density lipoprotein receptor comprises seven
      cysteine-rich repeats, which have been highly conserved through evolution. This
      domain mediates interactions of the receptor with two lipoprotein apoproteins,
      apo E and apo B-100, putatively through a calcium-dependent association of the
      ligands with a cluster of acidic residues on the receptor. The second repeat
      (rLB2) of the receptor binding domain has been expressed as a thrombin-cleavable
      GST fusion protein, cleaved, and purified. On oxidation the protein refolded to
      give a single peak on reverse-phase HPLC. The aqueous solution structure of rLB2
      has been determined using two-dimensional 1H NMR spectroscopy. In contrast to the
      amino-terminal repeat, rLB1, rLB2 has a very flexible structure in water.
      However, the conformation of rLB2 is markedly more ordered in the presence of a 4
      fold molar excess of calcium chloride; the proton resonance dispersion and the
      number of NOESY cross-peaks are greatly enhanced. The three-dimensional structure
      of rLB2, obtained from the NMR data by molecular geometry and restrained
      molecular dynamics methods, parallels that of rLB1, with an amino-terminal
      hairpin structure followed by a succession of turns. However, there are clear
      differences in the backbone topology and structural flexibility. As for rLB1, the
      acidic residues are clustered on one face of the module. The side chain of Asp
      37, which is part of a completely conserved SDE sequence thought to be involved
      in ligand binding, is buried, as is its counterpart (Asp 36) in rLB1. These
      results provide the first experimental support for the hypothesis that each of
      the repeats in the ligand-binding domain has a similar global fold but also
      highlight significant differences in structure and internal dynamics.

PMID- 7578054
TI  - Light-driven chloride ion transport by halorhodopsin from Natronobacterium
      pharaonis. 1. The photochemical cycle.
AB  - The photochemical cycle of the light-driven chloride pump, halorhodopsin from N.
      pharaonis, is described by transient optical multichannel and single-wavelength
      spectroscopy in the visible, and in the infrared. Titration of a blue-shift of
      the absorption maximum upon addition of chloride describes a binding site with a
      KD of 1 mM. The reaction sequence after the all-trans to 13-cis
      photoisomerization of the retinal in this chloride binding form is itself
      dependent on chloride. At 2 M chloride it is described by the scheme: HR-
      >K<==>L<==>N-->HR that relaxes in a few milliseconds, and is very similar to the
      photocycle of bacteriorhodopsin under conditions where the retinal Schiff base
      cannot deprotonate. At lower chloride concentrations, e.g., 0.1 M, however, a red
      shifted state termed O appears between N and HR, in equilibrium with N. The
      absorption spectra of K, L, N, and O are very similar to their counterparts in
      the bacteriorhodopsin photocycle. As in their equivalents in bacteriorhodopsin,
      in the N state the retinal is still 13-cis, but it is reisomerized in the O state
      to all-trans.

PMID- 7578055
TI  - Light-driven chloride ion transport by halorhodopsin from Natronobacterium
      pharaonis. 2. Chloride release and uptake, protein conformation change, and
      thermodynamics.
AB  - The photocycle of the light-driven chloride pump, N. pharaonis halorhodopsin, is
      described by the scheme HR-->K--><==>L<==>N<==>O<==>HR'-->HR. From the chloride
      dependencies of the rate constants in this model we identify the N-->O and O-
      >HR' reactions as the steps where chloride release and uptake occur,
      respectively, during the transport. The dependencies of the rate constants on
      temperature describe a thermodynamic cycle in which enthalpy-entropy conversion
      occurs in the O-->HR' reaction. The dependencies of the rate constants on
      hydrostatic pressure indicate that a substantial volume decrease occurs at the L-
      >N reaction, a result of a large-scale conformational change. This is the
      opposite of the volume increase in the photocycle of the proton pump,
      bacteriorhodopsin, that is implicated in the access change of the active site
      during the transport and the passage of a proton from the cytoplasmic surface to
      the active site. The results together suggest a chloride transport mechanism, in
      which the equivalents of all the ion transfer steps in bacteriorhodopsin occur
      but in the reverse sense, so as to cause the extracellular-to-cytoplasmic
      translocation of a chloride ion instead of the cytoplasmic-to-extracellular
      transport of a proton.

PMID- 7578053
TI  - Two tight binding sites for ADP and their interactions during nucleotide exchange
      in chloroplast coupling factor 1.
AB  - Chloroplast coupling factor 1 (CF1) deficient in its epsilon subunit was loaded
      with 2'(3')-O-trinitrophenyl-ADP (TNP-ADP), and the release of tightly bound TNP
      ADP was followed as a decrease in fluorescence. TNP-ADP could be exchanged for
      medium ADP, ATP, MgADP, and MgATP. The preferred substrate for exchange was
      MgADP, particularly in the presence of P(i). One nucleotide binding site
      contained ADP which was not displaced during TNP-ADP loading. When Mg2+ was bound
      at this site, complete exchange of bound TNP-ADP for medium nucleotide was
      prevented. This tightly bound MgADP was removed by incubation of the enzyme with
      EDTA. Tightly bound TNP-ADP was removed by high concentrations of sulfite,
      sulfate, or P(i) in the absence of medium nucleotide and free Mg2+, regardless of
      the bound Mg2+ content of the enzyme. Sulfite and P(i), in the presence of medium
      nucleotide and Mg2+, enabled complete exchange of tightly bound TNP-ADP. The
      combination of Mg2+ and sulfite, or Mg2+ and P(i), caused exchange of tightly
      bound ADP from two different sites. These results suggest that both sites
      exchange when the enzyme is fully active, and that at least three sites are
      likely to participate in catalysis.

PMID- 7578056
TI  - The interaction of epidermal growth factor with its receptor in A431 cell
      membranes: a stopped-flow fluorescence anisotropy study.
AB  - We describe a quantitative examination of the interaction of epidermal growth
      factor (EGF) with the EGF receptor using A431 cell membrane vesicles as a
      receptor source. Using T-format steady-state fluorescence anisotropy detection
      coupled with stopped-flow mixing, we measured the association and EGF-induced
      dissociation kinetics of fluorescein 5-isothiocyanate-labeled mEGF (FITC-EGF)
      with the EGF receptor over a wide range of FITC-EGF concentrations, membrane
      dilutions, and time scales (milliseconds to minutes). Fluorescence anisotropy
      based equilibrium binding titrations were also performed. All studies utilized
      the same receptor preparation, ligand preparation, and detection system. The
      entire data surface (approximately 78,000 data points) was simultaneously
      analyzed using global analysis techniques with a variety of kinetic models. Our
      analysis identified with a high level of confidence receptor populations with two
      association rate constants (k(on) = 1.2 x 10(6) M-1 s-1, 7.2 x 10(6) M-1 s-1) and
      three dissociation rate constants (k(off0 = 0.95 x 10(-2) s-1, 0.13 x 10(-2) s-1,
      0.32 x 10(-3) s-1), which reflect the presence of at least two distinct receptor
      populations in A431 cell membranes. Analysis of the kinetic data was found to be
      much more sensitive to the presence of multiple receptor populations than was the
      analysis of the equilibrium binding data.

PMID- 7578057
TI  - alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel
      selectivity.
AB  - We report the isolation and characterization of a novel nicotinic acetylcholine
      receptor (nAChR) ligand. The toxin is an 18 amino acid peptide and is the first
      reported alpha-conotoxin from an Atlantic fish-hunting Conus. The peptide was
      purified from the venom of Conus ermineus and is called alpha-conotoxin EI. The
      sequence diverges from that of previously isolated alpha-conotoxins. We
      demonstrate that this structural divergence has functional consequences. In
      Torpedo nAChRs, alpha-conotoxin EI selectively binds the agonist site near the
      alpha/delta subunit interface in contrast to alpha-conotoxin MI which selectively
      targets the alpha/gamma agonist binding site. In mammalian nAChRs alpha-conotoxin
      EI shows high affinity for both the alpha/delta and alpha/gamma subunit
      interfaces (with some preference for the alpha/delta site), whereas alpha
      conotoxin MI is highly selective for the alpha/delta ligand binding site. The
      sequence of the peptide is: Arg-Asp-Hyp-Cys-Cys-Tyr-His-Pro-Thr-Cys-Asn-Met-Ser
      Asn-Pro-Gln-Ile-Cys- NH2, with disulfide bridging between Cys4-Cys10 and Cys5
      Cys18, analogous to those of previously described alpha-conotoxins. This sequence
      has been verified by total chemical synthesis. Thus, alpha-conotoxin EI is a
      newly-available tool with unique structure and function for characterization of
      nAChRs.

PMID- 7578058
TI  - Modulation of annexin II tetramer by tyrosine phosphorylation.
AB  - Annexin II tetramer (AIIt) is a Ca(2+)-dependent phospholipid-binding
      phosphoprotein. In cells either expressing transforming protein tyrosine kinases
      or treated with growth factors such as PDGF, AIIt has been shown to contain
      increased levels of phosphotyrosine. Therefore, we have examined the effects of
      the in vitro phosphorylation of AIIt by pp60c-src on several activities of the
      protein. AIIt was phosphorylated by pp60c-src to 0.91 +/- 0.07 mol of
      phosphate/mol of AIIt (mean +/- SD). The protein tyrosine phosphorylation of AIIt
      completely inhibited the ability of the protein to bind to and bundle F-actin. In
      contrast, the phosphoprotein and native protein bound to purified adrenal medulla
      chromaffin granules with similar affinity; however, the chromaffin granule
      bridging activity of the phosphoprotein was abolished. The inhibition of the
      chromaffin granule bridging activity of the phosphoprotein could be partially
      reversed by the addition of millimolar Ca2+. Furthermore, the phosphorylation of
      AIIt by pp60c-src inhibited the in vitro ability of this annexin to form a
      complex consisting of plasma membrane, chromaffin granules, and AIIt. In addition
      to binding to biological membranes, some annexin proteins have been shown to
      possess carbohydrate-binding activity. Although native AIIt bound to a heparin
      affinity column, tyrosine phosphorylation of AIIt blocked the ability of the
      protein to bind to the heparin affinity column. These results suggest that the
      tyrosine phosphorylation of AIIt is a negative modulator of AIIt and that the
      dephosphorylation of AIIt might be necessary for activation of the protein.

PMID- 7578059
TI  - Metabolism of the polyubiquitin degradation signal: structure, mechanism, and
      role of isopeptidase T.
AB  - A necessary step in ubiquitin-dependent proteolysis is the addition of a
      polyubiquitin chain to the target protein. This ubiquitinated protein is degraded
      by a multisubunit complex known as the 26S proteasome. The polyubiquitin chain is
      probably not released until a late stage in the proteolysis by the proteasome. It
      is subsequently disassembled to yield functional ubiquitin monomers. Here we
      present evidence that a 93 kDa protein, isopeptidase T, has the properties
      expected for the enzyme which disassembles these branched polyubiquitin chains.
      Protein and cDNA sequencing revealed that isopeptidase T is a member of the
      ubiquitin specific protease family (UBP). Isopeptidase T disassembles branched
      polyubiquitin chains (linked by the G76-K48 isopeptide bond) by a sequential exo
      mechanism, starting at the proximal end of the chain (the proximal ubiquitin
      contains a free carboxyl-terminus). Isopeptidase T prefers to disassemble chains
      in which there is an intact and unblocked RGG sequence at the C-terminus of the
      proximal subunit. Rates of disassembly are reduced when G76 of the proximal
      ubiquitin is modified, for example, by ligation to substrate protein, by
      esterification, by replacement of the proximal glycine with alanine (G76A), or by
      truncation. Linear proubiquitin is only a poor substrate. Observed rates and
      specificity are consistent with isopeptidase T playing a major role in
      disassembly of polyubiquitin chains. The high discrimination against chains that
      are blocked or modified at the proximal end indicates that the enzyme acts after
      release of the chains from conjugated proteins or degradation intermediates.
      Thus, the proteolytic degradation signal is not disassembled by isopeptidase T
      before the ubiquitinated protein is degraded. These (and earlier) results suggest
      that UBP isozymes may exhibit significant substrate specificity, consistent with
      a role in the regulated catabolism of the polymeric ubiquitin, including the
      polyubiquitin protein degradation signal.

PMID- 7578060
TI  - Substrate-induced inactivation of a crippled beta-glucosidase mutant:
      identification of the labeled amino acid and mutagenic analysis of its role.
AB  - The beta-glucosidase from Agrobacterium sp. catalyzes the hydrolysis of beta
      glucosides via a covalent alpha-D-glucopyranosyl-enzyme intermediate involving
      Glu358. Hydrolysis of 2,4-dinitrophenyl beta-D-glucopyranoside by the low
      activity Glu358Asp mutant of Agrobacterium beta-glucosidase is accompanied by
      time-dependent inactivation of the enzyme. Through kinetic studies, labeling, and
      sequence analysis, inactivation is shown to be a consequence of the occasional (1
      time in 1100) attack of Tyr298 on the anomeric center of the substrate, in place
      of the catalytic nucleophile, with formation of a stable alpha-D-glucopyranosyl
      tyrosine residue. Tyr298 is conserved throughout family 1 of glycoside
      hydrolases, an indication of a possible role in catalysis. Results of a kinetic
      analysis of the Tyr298Phe mutant are consistent with a function of Tyr298 in both
      orienting the nearby nucleophile Glu358 and stabilizing its deprotonated state in
      the free enzyme.

PMID- 7578061
TI  - Identification of the acid/base catalyst in Agrobacterium faecalis beta
      glucosidase by kinetic analysis of mutants.
AB  - The catalytic mechanism of the retaining beta-glucosidase (Abg) from
      Agrobacterium faecalis involves a double-displacement process in which an alpha
      glucosyl-enzyme intermediate is formed with general acid catalytic assistance and
      then hydrolyzed with general base assistance. Glu170 was identified as an
      important residue, possibly the acid/base catalyst, on the basis of sequence
      alignments. This glutamate is conserved in almost all enzymes in family 1 of
      glycoside hydrolases. Detailed pre-steady-state and steady-state kinetic analyses
      of the mutant E170G suggested very strongly that Glu170 is the acid/base
      catalyst. First, kcat values were invariant with pH over the range of 5.0-9.0.
      Secondly, rates of formation of the glycosyl-enzyme, calculated from kcat/Km and
      k2, were similar to those of wild-type enzyme for substrates not requiring
      protonic assistance but dramatically reduced for those needing acid catalysis.
      Thirdly, addition of azide as a competitive nucleophile increased kcat values 100
      300-fold for substrates whose rate-limiting step is deglycosylation, yielding
      beta-glucosyl azide, but had no effect on the wild-type enzyme. Other anionic
      nucleophiles had similar, but less dramatic effects. Previous results [Gebler,
      J.C., et al. (1995) 34, 14547-14553] had indicated that Tyr298F is important for
      catalysis. The kinetic consequences of the mutations in the double mutant E170G
      Y298F are additive, resulting in a 10(6)-fold reduction in kcat values and
      allowing the accumulation of a stable (t1/2 > 7 h) glucosyl-enzyme intermediate.
      Thus, Glu170 and Tyr298 function independently, and a possible role for Tyr298 in
      modulating the pKa of the catalytic nucleophile is proposed.

PMID- 7578063
TI  - Characterization of the slow folding reactions of trp aporepressor from
      Escherichia coli by mutational analysis of prolines and catalysis by a peptidyl
      prolyl isomerase.
AB  - Escherichia coli trp aporepressor (TR) is a highly helical, dimeric protein whose
      folding has been shown to involve three phases whose relaxation times range from
      200 ms to 50 s at 25 degrees C and pH 7.6 [Gittelman, M. S., & Matthews, C. R.
      (1990) Biochemistry 29, 7011-7021]. All three phases are urea and protein
      concentration independent below 3 M urea, suggesting that cis/trans proline
      isomerization might limit the folding of TR under these conditions. This
      hypothesis was tested by measuring the sensitivity of the folding reaction to
      site-directed mutagenesis and to cyclophilin, a peptidyl-prolyl isomerase. Each
      of the four proline residues in TR was replaced singly as well as simultaneously,
      and the effects on the folding mechanism were assessed. All of these mutants,
      including the version lacking prolines (des-Pro TR), retain three slow,
      denaturant-independent folding phases similar to those observed for wild-type TR.
      However, the pattern of catalysis of the two slower folding phases in wild-type
      and mutant TRs by cyclophilin shows that cis/trans isomerization of the
      Thr44/Pro45 peptide bond can limit folding in proteins containing Pro45. The
      observation of three urea-independent, slow folding phases in des-Pro TR
      demonstrates that proline isomerization is not solely responsible for this
      complex folding behavior. Other types of isomerization or conformational
      rearrangement reactions appear to limit the folding of this dimeric protein under
      strongly folding conditions.

PMID- 7578062
TI  - Truncation and alanine-scanning mutants of type I adenylyl cyclase.
AB  - A variety of truncated constructs of type I and type II adenylyl cyclase have
      been synthesized in Sf9 cells using recombinant baculoviruses, as have a number
      of type I adenylyl cyclases with point mutations. Truncations indicate that the
      nonconserved C1b and C2b domains of adenylyl cyclase are not necessary for
      regulation of enzymatic activity by Gs alpha and forskolin. Point mutations
      demonstrate the requirement for both of the conserved (and homologous) domains of
      adenylyl cyclase (C1a and C2a) and the nonequivalence of these domains. Linkage
      of certain effects of mutations on the Km for substrate with alterations of the
      characteristics of P-site inhibition suggest that ATP and P-site inhibitors may
      bind to different conformations of the same site. However, other mutations
      affected only P-site inhibition. Although the mutations studied have not
      permitted assignment of unique functions to the two homologous domains, they have
      revealed novel phenotypes that appear to reflect the regulatory complexity of
      mammalian membrane-bound adenylyl cyclases, including the possibility of
      oligomerization of the enzymes.

PMID- 7578064
TI  - Nature and consequences of GroEL-protein interactions.
AB  - The importance of chaperonin-protein interactions has been investigated by
      analyzing the refolding of the barley chymotrypsin inhibitor 2 in the presence of
      GroEL. The chaperonin retards the rate of refolding of wild type and 32
      representative point mutants. The retardation of the rate drops to a finite level
      at saturating concentrations of GroEL, being lowered by a factor of 3-100,
      depending on the mutation. It is seen qualitatively that truncation of large
      hydrophobic side chains to smaller side chains weakens binding. Analysis of the
      magnitude of the rates of retardation shows further that hydrophobic and
      positively charged side chains tend to interact favorably with GroEL whereas
      negatively charged side chains tend to repel. There is an inverse correlation
      between the strength of hydrophobic interactions and the rate constant for
      refolding of the GroEL-complexed protein: the better the binding, the slower the
      folding. This shows directly that hydrophobic (and other favorable) interactions
      between the chaperonin and substrate are weakened during the refolding process
      and implies that unfolding can be catalyzed by the gain of such interactions.

PMID- 7578065
TI  - Effect of pH and insulin on fibrillogenesis of islet amyloid polypeptide in
      vitro.
AB  - Islet amyloid polypeptide (IAPP) is the constituent of amyloid deposits in
      pancreatic islets of type 2 diabetes in man, monkeys, and cats. This 37 amino
      acid peptide aggregates in vitro to form beta-pleated sheet fibrils. Rodent IAPP
      has a different amino acid sequence and does not form amyloid either in vitro or
      in vivo. Fibrillogenic properties of human IAPP (hIAPP) were determined in vitro.
      The effect of pH and time course of fibril formation was studied by light
      scattering spectroscopy. Aggregation of hIAPP1-37NH2 and hIAPPTyr20-29 (0.25
      mg/mL) was maximal at neutral/basic and acidic pH, respectively. The
      ultrastructure of hIAPP1-37NH2 fibrils (0.2 mg/mL) was examined using negative
      staining for electron microscopy. Short fibrils composed of 2 or more filaments
      were observed at pH 3-9 after 30 min incubation. At pH 7-9, IAPP fibrils formed a
      gel. After 6 months at pH 3, large sheets of parallel fibrils were seen. Specific
      binding of 125I-hIAPP1-37NH2 to preformed IAPP fibrils detected by quantitative
      autoradiography and radioassay was maximal at pH 3. Binding was enhanced by
      insulin (3.7 nmol/L) and unaffected by glucose, calcium, glucagon, and
      apolipoprotein E. 125I-hIAPP1-37NH2 bound specifically to islet amyloid in
      pancreatic tissue sections from type 2 diabetic patients. CONCLUSIONS: Binding to
      preformed IAPP fibrils is maximal at acid pH when hIAPP is largely in soluble
      form. IAPP is secreted together with insulin from the acidic secretory granules
      (pH 5.5) to the neutral pH of the extracellular space under normal conditions.
      These changes in pH together with increased accumulation of extracellular hIAPP
      in diabetes may promote amyloid formation.

PMID- 7578066
TI  - Preferred sites of glycosylphosphatidylinositol modification in folate receptors
      and constraints in the primary structure of the hydrophobic portion of the
      signal.
AB  - The divergent carboxyl-terminal signal peptides for glycosylphosphatidylinositol
      (GPI) membrane anchor attachment in folate receptor (FR) types alpha and beta
      were characterized. All of the candidate amino acid residues for GPI modification
      were identified and tested by substituting individually and in combination with
      amino acids that cannot be modified by GPI. Thus the GPI modification in FR-alpha
      was decreased to 22% by mutation of Ser234 to Thr but unaltered by changing the
      other candidate, Gly235, to Met. However, the double mutant FR-alpha Ser234
      Thr,Gly235-Met showed half of the GPI modification seen in FR-alpha Ser234-Thr.
      This result suggests that Ser234 is the preferred GPI modification site, while
      Gly235 is a minor, alternate GPI modification site. Similarly, in FR-beta,
      mutation of Asn230 to Gln decreased GPI modification to 32%, while mutation of
      the other candidate site, Gly237, to Met had no effect. However, mutation at both
      sites further reduced the GPI modification by a half. A five amino acid carboxyl
      terminal deletion (FR-beta delta 5) caused no decrease in the extent of GPI
      modification. However, the same deletion in FR beta Asn230-Gln decreased the
      residual GPI modification by 66%. These results suggest that Asn230 is the
      preferred GPI modification site in FR-beta, while Gly235 offers a minor alternate
      modification site; consistent with this conclusion is the fact that modification
      at the downstream site is hindered by its proximity to the carboxyl terminus in
      FR-beta delta 5. Further, the suggestion that the hydrophobic portion of the GPI
      signal is a random sequence of neutral amino acids with overall moderate
      hydrophobicity was tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578067
TI  - Specificity of minor-groove and major-groove interactions in a homeodomain-DNA
      complex.
AB  - To assess the importance of minor-groove and major-groove interactions in
      homeodomain-DNA recognition, the binding properties of variants of the altered
      specificity engrailed homeodomain, containing Lys50, and its DNA site TAATCC were
      determined. This homeodomain contacts bases in the minor groove of the DNA using
      Arg3 and Arg5 from its N-terminal arm and contacts bases in the major groove of
      the DNA using Ile47, Lys50, and Asn51 from its third alpha-helix. Mutation of
      Arg3 or Ile47 to alanine reduces binding affinity 10-20-fold while mutation of
      Arg5, Asn51, or Lys50 to alanine reduces binding affinity > 100-fold, indicating
      that both minor-groove and major-groove interactions contribute to the overall
      binding energy. Binding site selections and affinity measurements show that the
      homeodomain can also discriminate among different base pairs in the minor groove
      and the major groove. However, the interactions between Lys50 of the recognition
      helix and the major-groove edges of base pairs 5 and 6 are more specific than
      interactions mediated by Arg3 and Arg5 in the N-terminal arm and the minor-groove
      edges of base pairs 1 and 2.

PMID- 7578068
TI  - Design of lipoxin A4 stable analogs that block transmigration and adhesion of
      human neutrophils.
AB  - Lipoxins (LX) are bioactive eicosanoids that carry a tetraene structure and serve
      as regulators of inflammation, in part by inhibiting neutrophil migration and
      adhesion. Lipoxin A4 is rapidly regulated by conversion to inactive LX
      metabolites via local metabolism that involves dehydrogenation as the predominant
      route. Here, several LXA4 analogs were designed that resisted rapid conversion by
      both differentiated HL-60 cells and recombinant 15-hydroxyprostaglandin
      dehydrogenase, systems where native LXA4 is degraded within minutes. The rank
      order of conversion by recombinant dehydrogenase was LXA4 methyl ester > PGE2
      approximately PGE2 methyl ester > LXA4 >>> the novel LXA4 analogs. In addition,
      15(R/S)-methyl-LXA4, 15-cyclohexyl-LXA4, and 16-phenoxy-LXA4 proved to retain
      LXA4 bioactivity and inhibited neutrophil transmigration across polarized
      epithelial cell monolayers as well as adhesion to vascular endothelial cells.
      These results indicate that LXA4 analogs can be designed using these criteria to
      resist rapid transformation and to retain biological actions of native LXA4.
      Moreover, the results suggest that LXA4 stable analogs can be useful tools both
      in vitro and in vivo to evaluate LXA4 actions and therapeutic potential.

PMID- 7578069
TI  - Inhibition of herpes simplex virus replication by antisense oligo-2'-O
      methylribonucleoside methylphosphonates.
AB  - Antisense oligonucleoside methylphosphonates complementary to the 12 nucleotides
      found at the intron/exon junction of the splice acceptor site of herpes simplex
      virus type 1 (HSV-1) immediate early mRNAs 4 and 5 were synthesized. The
      methylphosphonate oligomers contained either 2'-deoxyribose nucleosides, d-OMPs,
      or 2'O-methylribose nucleosides, mr-OMPs. At 37 degrees C, the affinity of the mr
      OMP for a complementary 12-mer RNA target was approximately four times higher
      than that of the corresponding d-OMP as measured by a constant activity gel
      electrophoresis mobility shift assay. An mr-OMP whose sequence contained two
      mismatched bases did not bind to the RNA target under these conditions. The mr
      OMP also showed improved ability to inhibit HSV-1 replication in HSV-1 infected
      Vero cells in culture. Thus the IC50 of the mr-OMP was five times less than that
      of the d-OMP. No inhibition was observed by the mismatched mr-OMP, and no
      inhibition of herpes simplex virus type 2 (HSV-2) replication was observed with
      any of the oligomers. These results demonstrate a direct correlation between
      oligomer binding affinity and antisense activity in cell culture and suggest that
      oligo-2'-O-methylribonucleoside methylphosphonates are promising candidates for
      development of effective antisense reagents.

PMID- 7578070
TI  - Structure of the third cytoplasmic loop of bovine rhodopsin.
AB  - The three-dimensional high-resolution structure of rhodopsin is unknown, as is
      the case for almost all integral membrane patients. As part of an alternative
      approach to determine of membrane protein structure, we are pursuing the
      structure of cytoplasmic domains of this G-protein receptor. A peptide, rhoIII,
      with the sequence of the third cytoplasmic loop of bovine rhodopsin was
      synthesized. This soluble peptide was biologically active, inhibiting the light
      stimulated activation of the rod cell phosphodiesterase by rhodopsin in rod outer
      segment disks. Therefore rhoIII likely contains structural elements
      characteristic of native rhodopsin. The structure of rhoIII was determined by H
      nuclear magnetic resonance. A defined structure was obtained for about 70% of
      rhoIII. A model of a turn-helix-turn motif could then be proposed for the third
      cytoplasmic loop of rhodopsin, which suggested a molecular switch for activation
      of the G-protein by the receptor.

PMID- 7578071
TI  - The response regulators CheB and CheY exhibit competitive binding to the kinase
      CheA.
AB  - The autophosphorylating kinase CheA of the bacterial chemosensory signaling
      pathway donates a phosphoryl group to either of two regulator proteins, CheY or
      the receptor methylesterase (CheB). With isothermal titration calorimetry, it was
      demonstrated that CheA and CheA fragment composed of amino acid residues 1-233
      (CheA1-233) bound to CheY with similar dissociation constants of 2.0 and 1.2
      microM at 298 K, respectively, indicating that the CheY binding site is wholly
      within the 1-233 amino acid locus. CheB bound to CheA1-233 with a KD of 3.2
      microM, and also bound to intact CheA with the same affinity. CheY was found to
      complete with CheB for binding to CheA1-233, in spite of the low level of
      sequence identity between CheY and the regulatory domain of CheB. The competitive
      nature of CheY and CheB binding was determined in two independent sets of
      experiments: titration experiments in which either a CheB-CheA1-233 complex was
      titrated with CheY or CheB was titrated with a CheY-CheA1-233 complex, and
      competitive affinity chromatography experiments that used a Ni-NTA-chelating
      resin as an affinity matrix for complexes of the histidine-tagged CheA1-233
      fragment and CheY or CheB. The effects of phosphorylation, binding-site
      mutations, and active-site mutations were also studied to probe the influence of
      conformational changes in CheY as a regulatory mechanism of CheY-CheA
      Interactions. Phosphorylated CheY, in the presence of excess EDTA, was found to
      have a 2-fold lower affinity for CheA1-233, and 6 mM Mg2+ further reduced the
      affinity of phosphorylated CheY for CheA1-233 (ca. 3-fold), although Mg2+ on its
      own had no effect on the interactions of either CheB or CheY with CheA1-233. The
      data thus indicate that phosphorylated CheY has a significantly lower affinity
      for CheA under physiological conditions. The idea that phosphorylation may induce
      a significant conformational change, reducing the strength of the CheY-CheA
      interaction, is supported by the relative values of the association constants
      measured for CheY active-site and binding-site mutants. A binding-site mutation
      (A103V) in CheY, which is remote from the site of phosphorylation produced a 10
      fold reduction in Ka, whereas active-site mutations produced a modest (2-fold)
      reduction.

PMID- 7578072
TI  - Solution structure of a human cystatin A variant, cystatin A2-98 M65L, by NMR
      spectroscopy. A possible role of the interactions between the N- and C-termini to
      maintain the inhibitory active form of cystatin A.
AB  - The solution structure of a human cystatin A variant, cystatin A2-98 M65L, which
      maintains the full inhibitory activity of the wild-type protein, was determined
      at pH 3.8 by sD/3D heteronuclear double- and triple-resonance NMR spectroscopy.
      The structure is based on a total of 1343 experimental restraints, comprising
      1139 distance, 154 phi and chi 1 torsion angle restraints, and 50 distance
      constraints for 25 backbone hydrogen bonds. A total of 15 structures was
      calculated using the YASAP protocol with X-PLOR, and the atomic rms distribution
      about the mean coordinate positions for residues 8-93 was 0.55 +/- 0.10 A for the
      backbone atoms and 1.05 +/- 0.11 A for all heavy atoms. The structure consists of
      five antiparallel beta-sheets and two short alpha-helices. Comparison with the X
      ray structure of cystatin B in the papain complex shows that the conformation of
      the first binding loop is quite similar to that of cystatin A, with an rms
      deviation of 0.78 A for the backbone atoms in the 43-53 region (cystatin A
      numbering). The second binding loop, however, is significantly different in the
      two structures, with an rms deviation greater than 2 A. There are some other
      significant differences, especially for the N-terminal and alpha-helix regions.
      The overall structure of cystatin A is also compared with the recently reported
      NMR structure of the wild-type cystatin A (stefin A) at pH 5.5 (Martin et al.,
      1995) and reveals the following features. that differ in our structure from the
      previous one: (1) the N-terminal segment, which was unstructured in the previous
      report, folds over in close vicinity to the C-terminus, as revealed by the
      distinctive NOEs between those segments; (2) two discrete short alpha-helices
      linked by a type II reverse turn were found, instead of the continuous single
      alpha-helix with a slight kink shown in the previous structure; (3) the second
      binding loop, which was not well converged in the previous study at pH 5.5, is
      determined very well in our structure. The effect of the N-terminal truncation on
      the cystatin A structure was examined by comparing the 1H-15N HSQC spectrum of
      cystatin A2-98 with that of the cystatin A5-98 variant, which lacks the anti
      papain activity, revealing significant chemical shift differences in the residual
      N-terminal segment and the first binding loop, together with small shifts in the
      other parts.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7578073
TI  - Mechanism of ligand binding to Ni(II)-Fe(II) hybrid hemoglobins.
AB  - The geminate and bimolecular binding of CO, O2 and NO to [alpha-Ni(II)]2-[beta
      Fe(II)]2 and [alpha-Fe(II)]2-[beta-Ni(II)2] hybrid hemoglobins has been studied.
      Biomolecular reactions: At pH 6.6 and 20 degrees both hybrids bind CO at 0.15 x
      10(6) M-1 s-1. Reactions with oxygen: At pH 6.6 the on rates are 4.8 and 7.5 x
      10(6) M-1 S-1 for alpha- and beta-hybrids, respectively; the off rate is
      approximately 2 x 10(3) S-1 for both. At pH 8 the alpha-Fe shows cooperativity
      whereas the beta-hybrid does not. Nanosecond geminate reactions: Faster
      bimolecular rates correlate with larger geminate amplitudes; thus alpha-Fe
      hybrids have larger amplitudes, and O2 geminate amplitudes are larger than those
      with CO. At pH 8.50% of O2 recombines with the alpha-hybrid. With NO, nanosecond
      geminate recombination is observable only with the beta-hybrid. Picosecond
      reactions: alpha-Hybrids show picosecond recombination of O2. With NO, alpha
      hybrids recombine at 30 ns-1, beta-hybrids at 0.3 ns-1. The NO picosecond rates
      correlate with the molecular dynamics which shows ligands leaving the beta-Fe
      atom early and regularly, but remaining near the alpha-Fe atom. The results may
      be explained by assuming an interaction between the alpha-subunits giving rise to
      a high-affinity faster-reacting form, whereas the beta-subunits only become fast
      reacting when an R-T conformation change analogous to that of hemoglobin A takes
      place. A third allosteric state is postulated to explain the results.

PMID- 7578074
TI  - Heme stoichiometry of heterodimeric soluble guanylate cyclase.
AB  - The soluble form of guanylate cyclase (sGC) is to date the only definitive
      receptor for the novel signaling agent nitric oxide (.NO). .NO increases the Vmax
      of sGC by 100-200-fold, and it has been proposed that this activation occurs
      subsequent to the binding of .NO to a heme moiety on the enzyme. It has
      previously been demonstrated that the enzyme can be purified in a state
      containing as much as 1 heme per heterodimer. However, since the two subunits of
      the heterodimer display considerable homology, and the enzyme routinely loses
      heme upon purification, it has been unclear whether the native heme stoichiometry
      is 1 per heterodimer or 2 per heterodimer. Using a novel procedure, the enzyme
      has been purified to homogeneity from bovine lung in a state containing 1.52 +/-
      0.10 equiv of heme per heterodimer, indicating that the native heme stoichiometry
      is 2 per heterodimer. The .NO-activated specific activity of this enzyme is
      increased by 50% over that of enzyme containing 1 heme per heterodimer and is the
      highest specific activity ever observed for sGC. Spectrally only one type of heme
      is observed, indicating that both hemes in the heterodimer are in similar
      environments. It is concluded that each subunit of the heterodimer binds 1 equiv
      of heme at a site conserved between the two subunits. Alignment of the nine
      published cDNA sequences for sGC indicates that the heme binding domain is the
      central portion of each subunit, corresponding to residues 213-370 in the bovine
      beta 1 sequence.

PMID- 7578075
TI  - Influence of charge and polarity on the redox potentials of high-potential iron
      sulfur proteins: evidence for the existence of two groups.
AB  - We have investigated the HiPIPs from Ectothiorhodospira vacuolata (iso-1 and iso
      2), Chromatium vinosum, Rhodocyclus gelatinosus, Rhodocyclus tenuis (strain
      2761), Rhodopila globiformis, and Rhodospirillum salinarum (iso-2) by direct
      electrochemistry. Using a glassy carbon electrode with a negatively charged
      surface, direct, unpromoted electrochemistry is possible with the positively
      charged HiPIPs. With the negatively charged HiPIPs, the positively charged and
      flexible bridging promoter poly(L-lysine) is required. The stability of the
      response can be improved by morpholin, aspartate, tryptophan, or 4,4'-dipyridyl.
      These "stabilizers" prevent the blocking of the electrode by denatured protein.
      The redox potential of 500 mV found for R. salinarum iso-2 is the highest HiPIP
      potential reported. The presence of histidines in the sequence does not per se
      predict a pH-dependent redox potential. Only C. vinosum and R. gelatinosus HiPIPs
      show a weak but significant pH dependence with a difference of 35 mV between the
      low- and the high-pH form and maximum slopes of -20 mV/unit. The dependence of
      the midpoint potential on temperature and on ionic strength varies over the
      different HiPIPs. The dependence of the potentials on square root of I cannot be
      fully explained by the Debye-Huckel theory because the linearity exceeds the
      limiting concentration and only small negative slopes are observed (o to -28
      mV/square root of M) Combination of the sequences, the optical spectra, the
      overall charges, and the redox thermodynamics suggests that existence of two
      groups of HiPIPs. One group consists of Chromatium-like HiPIPs with redox
      potentials between 300 and 350 mV, modulated only by the solvation of the
      cluster. The second group is formed by Ectothiorhodospira-like HiPIPS with
      potentials between 50 and 500 mV, modulated by the overall charge of the peptide
      (25 mV/unit) and by the solvation of the cluster.

PMID- 7578076
TI  - Laser photolysis behavior of ferrous horseradish peroxidase with carbon monoxide
      and cyanide: effects of mutations in the distal heme pocket.
AB  - Native horseradish peroxidase and several forms with mutations in the distal heme
      pocket (His42Leu, His42Arg, and Arg38Leu) have been expressed in Escherichia
      coli. These enzymes have been purified and analyzed in terms of the room
      temperature recombination rate of carbon monoxide and cyanide after photolysis of
      the reduced forms. The recombinant wild-type ferrous form exhibited monophasic
      recombination of carbon monoxide with an observed bimolecular rate constant at pH
      8.5 of 4.4 x 10(3) M-1 s-1 which is essentially the same as the natural
      glycosylated form. This recombination rate constant increases in the mutants in
      the order WT < H42R < H42L << R38L. The value for R38L (5 x 10(6) M-1 s-1) is
      increased by 3 orders of magnitude relative to the wild-type and is similar to
      that for human hemoglobin [Mims et al. (1983) J. Biol. Chem. 258, 14219-14232].
      Cyanide recombination with the wild-type ferrous form at room temperature is
      biphasic at pH 6.5 but becomes more monophasic at pH 8.5, again similar to the
      behavior of the natural glycosylated form, although the Fe(2+)-cyano form of the
      recombinant enzyme appears to be more unstable at high pH. None of the mutant
      forms were able to bind cyanide in the ferrous state to any significant extent
      (Kdiss > 250 mM) when cyanide was added at a concentration (10-20 mM) sufficient
      to almost saturate the wild-type form (Kdiss approximately equal to 1 mM at pH
      7). This behavior contrasts with that of the oxidized forms of the mutants where
      increases in cyanide dissociation constants are smaller ( < 25 times).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578077
TI  - Isolation and structural characterization of different isoforms of the hypusine
      containing protein eIF-5A from HeLa cells.
AB  - Posttranslational modification of a specific lysine residue in eukaryotic
      initiation factor 5A (eIF-5A) is essential for cell viability and proliferation.
      The product of this modification is hypusine, an amino acid unique to eIF-5A. We
      have purified and characterized one major and three minor isoforms of human eIF
      5A from HeLa cells. The main form, which accounts for approximately 95% of the
      total eIF-5A, carries hypusine at position 50 and is amino-terminally acetylated
      as determined by amino acid composition analysis and electrospray ionization mass
      spectrometry. Analytical gel filtration indicates that this protein variant
      possesses a native apparent molecular weight that lies between that expected for
      a monomeric and dimeric form. Nevertheless, several experiments confirm this
      protein to be monomeric. It is further shown that eIF-5A have well-defined
      secondary structure. Both the far-UV circular dichroism spectrum as well as
      secondary structure predictions using different algorithms suggest this protein
      to have predominantly beta-sheet structure. Two plausible models for the packing
      of the secondary structure elements are presented. In contrast to the main form,
      all three minor isoforms of eIF-5A are characterized by acetylation of the
      epsilon-amino group of lysine at position 47. The minor isoforms are
      distinguishable by their state of modification of the lysine residue at position
      50. Whereas the main form occurs in both the cytoplasmic and the nuclear fraction
      of HeLa cells, the minor isoforms were not detectable in the preparation of the
      nuclear fraction. Therefore, acetylation of lysine at position 47 might play a
      controlling role in the distribution of the minor isoforms to the nucleus.

PMID- 7578078
TI  - The polypeptide chain of eukaryotic initiation factor 5A occurs in two distinct
      conformations in the absence of the hypusine modification.
AB  - Eukaryotic initiation factor 5A (eIF-5A) requires posttranslational modification
      of lysine at position 50 to hypusine for its biological activity. We have
      expressed an unmodified variant of eIF-5A in Escherichia coli and show that it
      has structural properties different from those of the native protein in terms of
      its near- and far-UV circular dichroism spectra and its equilibrium unfolding
      transition with guanidinium chloride. In contrast to the hypusine-modified
      protein, which unfolds in a two-state process, the complex unfolding transition
      of unmodified eIF-5A suggests that this variant occurs in two differently folded
      conformations, F1 and F2. Both conformations are populated under near
      physiological conditions at a ration of 60 to 40, respectively. Equilibrium
      unfolding consists of parallel events: unfolding of F1 to one or several
      intermediate states (I), and unfolding of F2 to the unfolded state (U). Although
      the establishment of each of these individual equilibria is fast, the
      interconversion is slow at guanidinium chloride concentrations between 0 M and 3
      M. Kinetic analysis reveals activation energies of 24.3 kcal mol-1 for the
      reaction of F1 and F2 and 24.1 kcal mol-1 for the reaction of F2 to F1. Both F1
      and F2 possess well-defined secondary and tertiary structure. However, the
      tertiary structures of the two conformations differ as indicated by their
      distinct near-UV circular dichroism spectra. These differences may be restricted
      to the C-terminal part of the protein as 2-dimensional 1H-NMR spectra of
      unmodified eIF-5A reveal no doubled set of proton resonances for aromatic amino
      acid and histidine residues, of which almost all are located in the N-terminal
      region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578080
TI  - Fourier transforms infrared difference spectroscopy of secondary quinone acceptor
      photoreduction in proton transfer mutants of Rhodobacter sphaeroides.
AB  - In order to investigate the changes of protonation or environment of carboxylic
      residues occurring upon photoreduction of the secondary quinone acceptor (QB) in
      the reaction center (RC) of the photosynthetic bacteria Rhodobacter sphaeroides
      2.4.1., we have performed light-induced Fourier transform infrared (FTIR)
      spectroscopy on RCs from wild-type (Wt) and several site-directed mutants. The
      FTIR QB-/QB spectra have been obtained at pH 7 upon single-saturating flash
      excitation for native RCs and RC mutants containing either a single-site
      mutation, with Gln at L212 (EQ L212), Asn at L213 (DN L213), or Asn at L210 (DN
      L210), or a double-site mutation with both Gln at L212 and Asn at L213 (EQ L212 +
      DN L213). The assignment of an IR band to the protonation/deprotonation of a
      particular carboxylic side chain was analyzed by combining the effects of site
      directed mutagenesis and 1H/2H isotope exchange. A positive band at 1728 cm-1 in
      the QB-/QB spectra was observed in Wt, DN L213, and DN L210 and was absent in the
      mutants EQ L212 and EQ L212 + DN L213. The intensity of the 1728 cm-1 band was
      significantly reduced in 2H2O, and a new feature appears at 1717 +/- 1 cm-1.
      Furthermore, the amplitude of the 1728 cm-1 band was similar in native and DN
      L210 RCs but was increased in DN L213. This band is attributed to partial proton
      uptake by Glu L212 estimated to be 0.3-0.4 H+/QB- in native and DN L210 RCs and
      O.5-0.6 H+/QB- in DN L213 RCs. In contrast, the FTIR QB-/QB spectra show no
      evidence for change of protonation or environment of Asp L213 upon QB- formation.
      The increased protonation of Glu L212 in DN L213 RCs is explained by a decreased
      Glu L212 pKa value due to the loss of a negatively charged Asp L213. Part of a
      small differential signal at 1732 (+)/1740 (-) cm-1 that is affected by 1H/2H
      exchange is tentatively assigned to an environmental shift of the protonated Asp
      L210. A negative signal at 1685 cm-1 is propose to arise from the absorption
      change of the amide I carbonyl mode of Glu L212.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7578081
TI  - The role of Thr268 in oxygen activation of cytochrome P450BM-3.
AB  - Cytochrome P450BM-3, a catalytically self-sufficient monooxygenase from Bacillus
      megaterium, catalyzes the omega-n (n = 1-3) hydroxylation of fatty acids in the
      presence of O2 and NADPH. Like most other P450s, cytochrome P450BM-3 contains a
      threonine residue (Thr268) in the distal I helix thought to be important for O2
      binding and activation. Thr268 has been converted to alanine and the enzymatic
      properties and heme domain crystal structure determined. Using sodium laurate as
      the substrate, the mutant exhibited slower rates of O2 and NADPH consumption. In
      addition, electron transfer is uncoupled from substrate hydroxylation as
      evidenced by the greater production of water and peroxide in the mutant compared
      to the wild-type enzyme. The crystal structure of the mutant reveals that the
      only changes in structure are confined to the site of mutation. These data
      indicate an important role for Thr268 in O2 binding and activation in the
      metabolism of sodium laurate by cytochrome P450BM-3.

PMID- 7578079
TI  - Time-resolved and steady-state spectroscopic analysis of membrane-bound reaction
      centers from Rhodobacter sphaeroides: comparisons with detergent-solubilized
      complexes.
AB  - The spectroscopic analysis of the antenna-deficient Rhodobacter sphaeroides
      strain RCO1 has been extended to an investigation of the kinetics and
      spectroscopy of primary charge separation. Global analysis of time-resolved
      difference spectra demonstrated that the rate of charge separation in membrane
      bound reaction centers is slightly slower than in detergent-solubilized reaction
      centers from the same strain. A kinetic analysis of the decay of the primary
      donor excited state at single wavelengths was carried out using a high repetition
      rate laser system, with the reaction centers being maintained in the open state
      using a combination of phenazine methosulfate and horse heart cytochrome c. The
      kinetics of primary charge separation in both membrane-bound and solubilized
      reaction centers were found to be non-monoexponential, with two exponential decay
      components required for a satisfactory description of the decay of the primary
      donor excited state. The overall rate of charge separation in membrane-bound
      reaction centers was slowed if the primary acceptor quinone was reduced using
      sodium ascorbate. This slowing was caused, in part, by an increase in the
      relative amplitude of the slower of the two exponential components. The
      acceleration in the rate of charge separation observed on removal of the reaction
      center from the membrane did not appear to be caused by a significant change in
      the electrochemical properties of the primary donor. The influence of the
      environment of the reaction center on primary charge separation is discussed
      together with the origins of the non-monoexponential decay of the primary donor
      excited state.

PMID- 7578082
TI  - Large complexes of beta-poly(L-malate) with DNA polymerase alpha, histones, and
      other proteins in nuclei of growing plasmodia of Physarum polycephalum.
AB  - Of the various cell types in the life cycle of Physarum polycephalum, only the
      growing plasmodium contains the unusual polyester beta-poly(L-malate). The nuclei
      exhibit large complexes of this polymer with nuclear proteins, among them DNA
      polymerase alpha, histones, and HMG-like proteins. The complexes are indicated by
      the results of size exclusion chromatography and chemical cross-linking with 1
      ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDC). After
      hydroxylaminolysis of the cross-linked polyester, the proteins are liberated and
      visualized on Western blots. The complexes of 1200-1400 kDa molecular mass exceed
      by far the size of free beta-poly(L-malate) and proteins. The observed variation
      in mass appears to be mainly a function of the kind and stoichiometry of the
      protein constituents and may explain the relatively high molecular mass in S
      phase and the low molecular mass during G2 phase of the mitotic cycle. The
      complexes are considerably stable at moderate ionic strength (100 mM KCl). Also,
      endogenous beta-poly(L-malate) does not exchange with added beta-[14C]poly(L
      malate) during the lysis of the nuclei and the sample preparation. The complexes
      are dissociated at elevated concentrations of KCl, in the presence of spermine
      hydrochloride, or by treatment with DEAE/cellulose. Available evidence indicates
      that beta-poly(L-malate) may be involved in the maintenance of the plasmodial
      state of P. polycephalum.

PMID- 7578083
TI  - A cytosine methyltransferase converts 5-methylcytosine in DNA to thymine.
AB  - Sites of cytosine methylation are known to be hot spots for C.G to T.A mutations
      in a number of systems, including human cells. Traditionally, spontaneous
      hydrolytic deamination of 5-methylcytosine to thymine has been invoked as the
      cause of this phenomenon. We show here that a bacterial cytosine
      methyltransferase can convert 5-methylcytosine in DNA to thymine and that this
      reaction creates a mutational hot spot at a site of DNA methylation. The reaction
      is fairly insensitive to the methyl donor in the reaction, S-adenosylmethionine.
      In many cancers, the most frequent class of mutations is C to T changes within CG
      dinucleotides of the tumor suppressor gene p53. Because of the similarities of
      the reaction mechanisms of mammalian and bacterial enzymes and the physiology of
      the cancer cells, this reaction is expected to contribute to mutations at CG
      dinucleotides in precancerous cells.

PMID- 7578084
TI  - Oxidation of thymine to 5-formyluracil in DNA: mechanisms of formation,
      structural implications, and base excision by human cell free extracts.
AB  - Oxidative agents produce several different types of base modifications in DNA,
      and only a few of these have been properly characterized with respect to
      mechanisms of formation and biological implications. We have established a
      procedure using neutral thermal hydrolysis and reverse phase high-performance
      liquid chromatography to determine the content of the oxidation product 5
      formyluracil (5-foU) in DNA. With this method, it is shown that 5-foU residues
      are formed with high frequency from thymine by quinone-sensitized UV-A
      photooxidation. Since 5-foU is also induced by ionizing radiation, it appears to
      be formed under conditions where thymidine radical cations are generated and
      react with molecular oxygen. It was previously shown that 5-foU is formed
      directly from [methyl-3H]thymine residues in radioactively labeled DNA by two
      consecutive transmutations of 3H to 3He. The theoretical basis for the kinetics
      of such conversion is presented in this paper, and the calculated yields are
      confirmed experimentally by measuring the content of 5-foU in [methyl-3H]thymine
      labeled DNA aged for different time periods. Such DNA contains virtually only 5
      (hydroxymethyl)uracil and 5-foU, apart from normal bases, and is therefore very
      useful for the investigation of repair enzyme activities involved in the repair
      of 5-foU-containing DNA. Using this substrate, a DNA glycosylase activity was
      identified in human cell extracts for the removal of 5-foU.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7578085
TI  - Template recognition by an RNA-dependent RNA polymerase: identification and
      characterization of two RNA binding sites on Q beta replicase.
AB  - Two different SELEX protocols were used to generate two classes of RNA ligands
      that bound Q beta replicase with nanomolar equilibrium dissociation constants.
      One set of RNAs appeared to exist as pseudoknots with conserved loop sequences.
      These ligands bound Q beta replicase and ribosomal protein S1 with equal
      affinities, indicating that the RNAs bind the replicase through its S1 subunit.
      The second class of ligands bound the replicase via a pyrimidine rich region. The
      two sets of ligands did not compete for binding to Q beta replicase,
      demonstrating that the two RNA families bind unique sites on the phage
      polymerase. Because the second class of ligands bound ribosomal protein S1 very
      poorly, it is likely that the second RNA binding site is located on one of the
      three remaining replicase subunits. Published sequences of RNAs replicated by Q
      beta replicase possess similarities to the two classes of RNA ligands, providing
      a possible solution to the question of template recognition by the phage
      polymerase.

PMID- 7578086
TI  - Selection and characterization of RNAs replicated by Q beta replicase.
AB  - RNAs replicated by Q beta replicase were isolated from two random sequence RNA
      populations (one 56 nucleotides in length, the second 83) using a
      replication/dilution protocol. The selected molecules were cloned and sequenced,
      generating data set of 54 replicatable RNAs bound with higher affinity to Q beta
      replicase than did the random populations from which they were selected. Deletion
      analyses on two of the molecules indicated that internal regions of the RNAs were
      responsible for the specific binding of Q beta replicase. Truncated molecules
      representing the minimized RNA binding sites could inhibit replication of the
      full-length molecules, apparently by obstructing their binding to the replicase.
      The binding regions of the two RNAs were dominated by extended runs of
      pyrimidines. Similar C/U-rich regions existed in 85% of the sequences in the data
      set as well as in all of the previously published replicatable sequences.
      Mutation of the polypyrimidine domain of one of the replicatable sequences
      reduced the affinity of the molecule for Q beta replicase by 10-fold and
      completely abolished its ability to be replicated.

PMID- 7578087
TI  - DNA adducts of cis-diamminedichloroplatinum(II) and its trans isomer inhibit RNA
      polymerase II differentially in vivo.
AB  - The effects of cis-diamminedichloroplatinum(II) (cis-DDP) and trans-DDP adducts
      on mammalian transcription in vivo have been investigated. A plasmid containing
      the beta-galactosidase (beta-gal) reporter gene was modified with either of the
      two platinum compounds and transfected into human or hamster cell lines. A 2-3
      fold higher level of transcription was observed in both cell lines from plasmids
      containing trans-DDP adducts as compared to plasmids modified by cis-DDP. This
      difference in transcriptional activity was not decreased in human and rodent
      nucleotide excision repair deficient cell lines, indicating that more efficient
      excision repair of the trans-DDP adducts was not the cause of its lower ability
      to block transcription in this assay. For this conclusion to be valid, it is
      assumed that trans-DDP adducts are repaired primarily by the nucleotide excision
      repair pathway, as is the case with the adducts of cis-DDP. The possibility that
      trans-DDP adducts are preferentially bypassed by RNA polymerase was examined by
      monitoring the elongation of beta-gal mRNA on damaged templates in vivo. Nascent
      beta-gal mRNA transcripts were recovered from excision repair deficient xeroderma
      pigmentosum A cells transfected with platinated plasmids, and the extent of RNA
      synthesis was measured by using ribonuclease protection. Fourfold more trans-DDP
      than cis-DDP adducts were required to inhibit transcription elongation by 63%.
      RNA polymerase II bypassed cis- and trans-DDP DNA adducts with efficiencies of 0
      16% and 60-70%, respectively. These data provide insight into the differential
      toxicity of the two platinum isomers.

PMID- 7578088
TI  - Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site
      solvent structure and binding mode of L-leucinal, a gem-diolate transition state
      analogue, by X-ray crystallography.
AB  - The three-dimensional structures of bovine lens leucine aminopeptidase (blLAP)
      complexed with L-leucinal and of the unliganded enzyme have been determined at
      crystallographic resolutions of 1.9 and 1.6 A, respectively. Leucinal binds as a
      hydrated gem-diol to the active site of b1LAP), resembling the presumed gem
      diolated intermediate in the catalytic pathway. One hydroxyl group bridges the
      two active site metal ions, and the other OH group is coordinated to Zn1. The
      high-resolution structure of the unliganded enzyme reveals one metal-bound water
      ligand, which is bridging both zinc ions. Together, these structures support a
      mechanism in which the bridging water ligand is the attacking hydroxide ion
      nucleophile. The gem-diolate intermediate is probably stabilized by four
      coordinating bonds to the dizinc center and by interaction with Lys-262 and Arg
      336. In the mechanism, Lys-262 polarizes the peptide carbonyl group, which is
      also coordinated to Zn1. The Arg-336 side chain interacts with the substrate and
      the gem-diolate intermediate via water molecules. Near Arg-336 in the b1LAP
      leucinal structure, an unusually short hydrogen bond is found between two active
      site water molecules.

PMID- 7578089
TI  - Spin-labeled psoralen probes for the study of DNA dynamics.
AB  - Six nitroxide spin-labeled psoralen derivative have been synthesized and
      evaluated as probes for structural and dynamic studies. Sequence specific
      photoaddition of these derivatives to DNA oligonucleotides resulted in site
      specifically cross-linked and spin-labeled oligomers. Comparison of the general
      line shape features of the observed electron paramagnetic resonance (EPR) spectra
      of several duplexes ranging in size from 8 to 46 base pairs with simulated EPR
      spectra indicate that the nitroxide spin-label probe reports the global tumbling
      motion of the oligomers. While there is no apparent large amplitude motion of the
      psoralen other than the overall tumbling of the DNA on the time scales
      investigated, there are some indications of bending and other residual motions.
      The (A)BC excinuclease DNA repair system detects structural or dynamic features
      of the DNA that distinguish between damaged and undamaged DNA and are independent
      of the intrinsic structure of the lesion. NMR studies have shown that psoralen
      cross-linked DNA has altered backbone dynamics and conformational populations in
      the immediate vicinity of the adduct [Emsley et al. (1993) J. Am. Chem. Soc. 115,
      7765-7771; Spielmann et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 2345-2349].
      We suggested that the signal for recognition of a lesion to be repaired is in the
      sugar--phosphate backbone and not in the damaged base(s).

PMID- 7578090
TI  - FTIR study of a nonclassical dT10*dA10-dT10 intramolecular triple helix.
AB  - Many early investigations on triple helices have been devoted to the study of the
      triplex formed by dT*dA-dT base triplets in which the third strand is oriented
      parallel to the dA strand. We now describe an intramolecular triple helix with
      dT*dA-dT base triplets in which the pyrimidine third strand is oriented
      antiparallel, formed by folding back twice the tridecamer dT10-linker-dA10-linker
      dT10 (linker = pO(CH2CH2O)3p). Third-strand base pairing to the target strand,
      sugar conformation, and thermal denaturation of the triplex have been studied by
      Fourier transform infrared spectroscopy. Our results confirm than when the third
      strand orientation is reversed from parallel to antiparallel with respect to the
      target strand, the third-strand hydrogen-bonding scheme is changed from Hoogsteen
      to reverse Hoogsteen. The sugar conformation in this triple helix is of the S
      type (C2'endo/anti, B family form) from all strands. Our results are discussed
      with respect to models for triplexes proposed as intermediates in homologous
      recombination [Zhurkin, V.B., Raghunathan, G., Ulyanov, N.B., Camerini-Otero,
      R.D., & Jernigan, R.L. (1994) J. Mol. Biol. 239, 181-200].

PMID- 7578092
TI  - Binding of heavy-chain and essential light-chain 1 of S1 to actin depends on the
      degree of saturation of F-actin filaments with S1.
AB  - The interaction of heavy-chain isoforms of myosin subfragment-1 with actin was
      examined by cross-linking with carbodiimide (EDC). The heavy chain of S1 could be
      cross-linked to a single actin molecule through sites on either 20 or 50 kDa
      proteolytic domains, resulting in complexes which migrated in an 8%
      polyacrylamide gel in the presence of Tricine buffer with an apparent molecular
      mass (M(app)) of 150 or 160 kDa, respectively. Cross-linking of S1 through both
      sites to two actins produced a complex migrating with an M(app) of 210 kDa. Cross
      linking of the S1(A1) isoform [but not S1(A2)] to F-actin produced four
      additional peptides with M(app) values of 64, 160, 185, 210, and 235 kDa
      complexes was almost inhibited at a high degree of saturation while the
      inhibition of the 150 kDa product was relatively small. At a low degree of
      saturation, the ratio of 150 to 160 kDa complexes was 1. Cross-linking between
      the S1 isoforms and regulated F-actin was not affected by Ca2+. These data show
      that contact of the S1 to one actin protomer is through a site on the 20 kDa
      fragment and to the second actin protomer through the sites located on the 50 kDa
      fragment and on the essential light-chain 1. At nonphysiological conditions of
      full saturation of actin filaments with myosin heads, the binding of heavy chain
      at S1 and of A1 to the second actin could be almost abolished.

PMID- 7578091
TI  - Modulation of phospholipase A2: identification of an inactive membrane-bound
      state.
AB  - Phospholipase A2-catalyzed hydrolysis of vesicular phospholipid has been used to
      model the modulation of an enzyme's function by membrane properties.
      Phospholipase A2's (PLA2) kinetics toward large unilamellar vesicles (LUV)
      composed of dipalmitoylphosphatidylcholine (DPPC) are anomalous; these is a slow
      initial phase of catalysis (a lag) which ends abruptly with a sudden increase in
      the catalytic rate (a burst). The sudden increase in activity due to the
      accumulation of a critical mole fraction of reaction products and substrate
      undergoes compositional phase separation. In this work, we address the molecular
      details of the coupling between compositional phase separation and activation of
      PLA2. A prominent model for this coupling is that compositional phase separation
      leads to a surface for which PLA2 has increased affinity, resulting in the
      recruitment of PLA2 from solution to the surface. Here, we show that the bulk of
      PLA2 is associated with the membrane at a time well before the abrupt increase in
      catalytic rate. This finding indicates that there must be a relatively inactive,
      membrane-bound state. Furthermore, PLA2's kinetics are anomalous even when the
      substrate comprises a surface to which PLA2 is bound throughout the time course.
      With DPPC LUV as the substrate, detailed time courses show that the description
      of the time course as a lag and a burst is inadequate. Instead, the time course
      consists of multiple phases of acceleration and deceleration. The data presented
      here suggest that all these various changes in catalytic rate may be due to
      product-induced changes in membrane properties. In particular, we suggest that
      nonequilibrium, microheterogeneities of lipid composition may underlie these very
      complicated kinetics.

PMID- 7578093
TI  - Purification and characterization of subtilisin cleaved actin lacking the segment
      of residues 43-47 in the DNase I binding loop.
AB  - The protease subtilisin has been reported to cleave skeletal muscle G-actin
      between Met 47 and Gly 48 generating a core fragment of 33 kDa and a small N
      terminal peptide, which remains attached to the core fragment [Schwyter, D.
      Phillips, M., & Reisler, E. (1989) Biochemistry 28, 5889-5895]. However, amino
      acid sequencing and mass spectroscopy of subtilisin cleaved-actin revealed two
      cleavage sites, one between Met 47 and Gly 48 and a second between Gly 42 and Val
      43, generating an actin core of 37 kDa and a nicked 4.4 kDa N-terminal peptide.
      Here we describe a procedure for purifying the actin core fragment and the
      attached N-terminal peptide from the linking pentapeptide comprising amino acid
      residues 43-47 under native conditions by anion exchange chromatography. After
      removal of the pentapeptide, the salt-induced polymerization of actin was
      abolished. However, the purified fragments could be polymerized by addition of
      salt plus myosin subfragment 1 or salt plus phalloidin as shown by sedimentation
      and fluorescence increase using N-(1-pyrenyl)iodoacetamide labeled actin. These
      results confirm earlier reports proposing that cleavage in the DNase I binding
      loop is affecting the ion induced polymerization of actin [Higashi-Fujime, S., et
      al. (1992) J. Biochem. (Tokyo) 112, 568-572; and Khaitlina, S., et al. (1993)
      Eur. J. Biochem. 218, 911-920]. Monomeric and filamentous subactin exhibited
      reduced abilities to inhibit deoxyribonuclease I (DNase I) and to stimulate the
      myosin subfragment 1 ATPase activity. Direct binding of subactin to DNase I was
      verified by gel filtration and to myosin subfragment 1 by affinity
      chromatography, chemical cross-linking, and electron microscopy.

PMID- 7578094
TI  - Characterization of pp60c-src tyrosine kinase activities using a continuous
      assay: autoactivation of the enzyme is an intermolecular autophosphorylation
      process.
AB  - A continuous assay for pp60c-src tyrosine kinase (srcTK) was developed. A lag in
      phosphorylation of the peptide RRLIEDAEYAARG was observed that could be
      eliminated by preincubation with MgATP. The induction time for this lag was
      dependent upon MgATP and srcTK concentrations. When autophosphorylation was
      monitored by 32P incorporation from [gamma-32P]ATP, a lag in the time course was
      also observed. These results demonstrate that autoactivation is an intermolecular
      process. The electrospray ionization mass spectrum of the enzyme before and after
      activation demonstrated an increase in the phosphorylation state of the enzyme
      after incubation with MgATP. The delta 85-N-terminal mutant protein and a full
      length G2A pp60c-src mutant, which removes the myristylation site, used in these
      studies were partially phosphorylated on Y338 and Y530 as isolated. This is the
      first report of phosphorylation on Y338, but the significance of this site of
      phosphorylation is unknown. These phosphorylations were insufficient to active
      the enzyme for transfer of the gamma-phosphoryl of MgATP to the peptides. The
      unphosphorylated enzyme initially present was converted to a monophosphorylated
      species upon treatment with MgATP. Y-419 phosphorylation was evident only after
      treatment with MgATP. These data are consistent with autophosphorylation on Y-419
      as predicted. Intermolecular autophosphorylation is consistent with the ability
      of srcTK to dimerize, which is analogous to activation of receptor tyrosine
      kinases such as the EGF receptor kinase in response to growth factors. These
      results indicate that dimerization leading to activation does not require binding
      to the membrane or a hydrophobic N-terminus in the case of srcTK.

PMID- 7578095
TI  - Examination of the dephosphorylation reactions catalyzed by pp60c-src tyrosine
      kinase explores the roles of autophosphorylation and SH2 ligand binding.
AB  - pp60c-src tyrosine kinase (srcTK) catalyzes the dephosphorylation of
      phosphotyrosine-containing peptides, including phosphopeptides that bind with
      high affinity to the src SH2 domain. The mechanism for these dephosphorylation
      reactions was investigated. Dephosphorylation was inhibited by a competitive
      inhibitor for the ATP binding site. In the presence of ADP, dephosphorylation of
      phosphopeptide substrates is primarily due to the reversal of the kinase
      reaction. Autoactivated and unactivated srcTK both catalyzed the reverse of the
      kinase reaction; however, autoactivated srcTK displayed an increase in kcat of
      approximately 4-11-fold relative to unactivated srcTK, depending on the reaction
      conditions. Autoactivation of srcTK does not affect the Km's for MgADP or
      phosphopeptide (FGE)3-pY-(GEF)2GD. Unphosphorylated srcTK becomes phosphorylated
      during the reverse of the kinase reaction upon accumulation of free MgATP. In the
      presence of MgATP, srcTK also dephosphorylates peptide substrates, by first
      hydrolyzing MgATP to MgADP. Binding of phosphotyrosine peptide ligands to the src
      SH2 domain stimulated the rate of MgATP hydrolysis approximately 2-fold, but had
      not effect on the Km for MgATP. These data suggest that autophosphorylation of
      tyrosine 419 is not required for nucleotide or peptide binding, or catalysis
      involving small peptide substrates. In addition, these results suggest that both
      the forward and the reverse src tyrosine kinase reactions may be important in
      regulating the intracellular levels of protein tyrosine phosphorylation.

PMID- 7578096
TI  - A suggested mechanism for the catalytic cycle of cytochrome bd terminal oxidase
      based on kinetic analysis.
AB  - The apparent oxygen affinity of cytochrome bd from Escherichia coli and
      Azotobacter vinelandii has been measured using oxymyoglobin as a sensitive
      monitor of oxygen concentration. In membrane preparations, the Km(O2) and
      respiratory rate varied with the nature of the primary substrate used (malate,
      lactate, reduced nicotinamide adenine dinucleotide (NADH), or ubiquinol-1). At
      maximum respiratory rates, the Km(O2) for cytochrome bd from A. vinelandii was
      4.1 microM, approximately 2 times higher than the corresponding value for the E.
      coli enzyme. There were no significant differences between the Km(O2) values for
      membrane-bound and purified cytochrome bd from A. vinelandii when ubiquinol-1 was
      used as primary substrate. The kinetic parameters Km(O2) and Vmax provide a value
      of 2.8 x 10(8) M-1 s-1 for the bimolecular rate constant for oxygen reaction with
      the enzyme, suggesting that this reaction is diffusion-controlled. Kinetic
      analysis indicates a mechanism involving a ternary complex. A scheme for the
      reaction mechanism of cytochrome bd is proposed.

PMID- 7578097
TI  - Catalysis sensitive conformational changes in soybean lipoxygenase revealed by
      limited proteolysis and monoclonal antibody experiments.
AB  - Soybean lipoxygenases catalyze lipid hydroperoxidation of polyunsaturated fatty
      acids. Putative ligand mediated conformational changes in soybean lipoxygenase 3
      (L3) were studied by a combination of limited proteolysis and a series of
      monoclonal antibodies that recognize discontinuous epitopes and alter catalysis
      (inhibition and activation). Trypsin cleaved L3 (97 kDa) into C-terminal 60 kDa
      and N-terminal 37 kDa fragments. The 37 kDa fragment was obtained from a 38 kDa
      fragment formed initially. Using protein footprinting, the epitopes of the
      antibodies were mapped to the 37 kDa fragment. Proteolysis in the presence of a
      substrate analog inhibitor, oleic acid, generated the 60 and the 38 kDa fragments
      only. No further proteolysis of the 38 kDa fragment was seen even after prolonged
      incubation. This was not a detergent effect since the altered proteolysis was not
      obtained in the presence of SDS or Tween 20. Binding of a monoclonal antibody to
      L3 in the presence of oleic acid was substantially reduced providing additional
      evidence for a conformational change induced by the oleic acid-lipoxygenase
      interaction. These observations are interpreted using the recently solved three
      dimensional structure of L3. It is apparent that while the protein is composed of
      a small N-terminal beta-barrel domain and a large principally alpha-helical C
      terminal domain, proteolysis does not take place at a linking region between the
      two domains. The proteolysis results makes it clear that the smaller domain is
      connected across the entire length of the larger domain to a narrow, tongue-like
      projection that extends into the vicinity of the entrance to the proposed
      substrate binding channel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578098
TI  - Kinetics of the reaction of a myelin basic protein peptide with soluble IAu.
AB  - The kinetics of formation and dissociation of IAu-peptide complexes have been
      examined in the absence of detergent, using a glycosylphosphatidylinositol (GPI)
      linked form of IAu. The GPI-linked form contains a lipid membrane anchor which
      can be specifically cleaved by phosphatidylinositol-specific phospholipase C to
      yield a water-soluble form of IAu. We find rapid binding of the myelin basic
      protein (MBP) peptide analogue Ac(1-14)A4C15 to IAu, as well as rapid
      dissociation of IAu-MBP peptide complexes at neutral pH in the absence of
      detergent. The reaction kinetics of the water-soluble and detergent-solubilized
      complexes are the same to within experiment error. In the presence of this MBP
      peptide, Ac(1-14)A4C15, cells transfected with native IAu as well as cells
      transfected with a GPI-linked form of IAu are functional in stimulating T-helper
      hybridoma cells.

PMID- 7578099
TI  - pH dependence of specific divalent anion binding to the N-lobe of recombinant
      human transferrin.
AB  - The binding of the two synergistic anion mimics, phosphate and sulfate, and of
      the synergistic anions, malonate and oxalate, to the N-lobe of recombinant human
      serum transferrin (hTF/2N) wild-type and H207E mutant protein was assessed by
      difference ultraviolet (UV) spectroscopy at 246 nm as a function of pH. The
      absolute values of both the maximum delta epsilon 246 and the Kd decreased with
      decreasing pH. A plot of -log Kd vs pH gave a straight line with a slope of -1.0.
      Furthermore, the sum of -log Kd and pH is a constant for each anion binding to
      each protein. We interpret these data to mean that each anion binds in divalent
      form along with an H+. The binding equilibrium then appears to be H+ + hTF/2N +
      X2- reversible K' H-hTF/2N(X) and log K' = -log Kd + pH. A plot of delta epsilon
      246 vs pH was sigmoidal with a pKa = 7.4 for both proteins with phosphate and
      sulfate. When synergistic anions were used with hTF/2N, malonate and oxalate gave
      pKas of ca. 6.9 and 7.1 for dependence of delta epsilon 246 on pH, but values of
      7.3 and 7.6 for the H207E mutant protein. In an attempt to locate the anion
      binding site in hTF/2N, the binding of sulfate to the single point mutants of the
      N-lobe of human transferrin, K296E, K296Q, and K206Q, was carried out by
      difference UV spectroscopy at pH 7.4. In the case of K296E, sulfate binding gave
      delta epsilon 246 = 0, while for K296Q, it gave a slightly positive delta epsilon
      246.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578100
TI  - Stabilization of triple-helical nucleic acids by basic oligopeptides.
AB  - Intermolecular triplex DNA is stabilized by metal cations and polyamines which
      reduce repulsion between the negatively charged phosphates of the three nucleic
      acid strands. We use a quantitative chemical-probing assay involving protection
      of duplex guanines in a homopyrimidine.homopurine (Py.Pu) sequence from dimethyl
      sulfate modification to study effects of basic oligopeptides on the stability of
      triplex DNA. An intermolecular protonated pyrimidine.purine.pyrimidine (Py.Pu*Py)
      triplex formed readily between a duplex DNA region and a 14-mer pyrimidine
      triplex-forming oligonucleotide (TFO) at pH 5. The triplex was stabilized at pH
      by the addition of magnesium ions. In the presence of spermine and lysine-rich
      peptides, the intermolecular triplex was stabilized up to pH 6.5-7.0. The
      effective peptide concentration required for stabilization was 10(-5)-10(-2) M.
      Of the basic peptides studied, pentalysine (Lys-Lys-Lys-Lys-Lys) was the most
      effective triplex stabilizer. It was effective at concentrations which are lower
      than those required for Lys-Gly-Lys-Gly-Lys and Lys-Ala-Lys-Ala-Lys and are
      similar to active concentrations of spermine. Basic peptides were more effective
      at stabilizing a Py.Pu*Py triplex than a pyrimidine.purine.purine (Py.Pu*Pu)
      triplex. At 1 mM, Lys-Lys-Lys-Lys-Lys stabilized the Py.Pu*Pu triplex at a level
      comparable to stabilization by Mn2+ and spermine, whereas Lys-Gly-Lys-Gly-Lys and
      Lys-Ala-Lys-Ala-Lys resulted in weaker TFO binding. The concentration of TFOs
      required to form triplex DNA were significantly reduced in the presence of
      peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578101
TI  - Binding sites of monoclonal antibodies and dihydropyridine receptor alpha 1
      subunit cytoplasmic II-III loop on skeletal muscle triadin fusion peptides.
AB  - Triadin binds to the dihydropyridine receptor (DHPr) and the junction foot
      protein (JFP) in Western blot protein overlay experiments. Fusion peptides were
      synthesized using an expression system, pGSTag, which includes a protein kinase A
      phosphorylation site. Expressed peptides are DHPr664-799 encoding rabbit skeletal
      DHPr alpha1 subunit amino acids 664-799, triadin 1 (1-49), triadin 2 (68-389),
      triadin 2' (110-389), triadin 2a (68-278), triadin 2a1 (67-163), triadin 2a2 (165
      240), triadin 2b (242-389), triadin 2b1 (242-299), triadin 3 (370-706), triadin
      3a (370-562), triadin 3b (551-706), triadin 3b1 (551-672), and triadin 3b2 (673
      706) (the numbers in parentheses correspond to the amino acid sequence of
      triadin). The triadin monoclonal antibodies, GE4.90 and AE8.91, bind to intact
      triadic vesicles as well as to vesicle fragments prepared after treatment with
      Triton X-100, indicating that they have cytoplasmic epitopes. MAb AE8.91 binds to
      triadin 2, 2', 2a, and 2a1, while mAb GE4.90 binds to triadin 3, 3b, and 3b2
      indicating that residues 110-163 and the C-terminal 34 amino acids contain
      cytoplasmic domains. Radiolabeled DHPr664-799 binds to triadin in intact vesicles
      under nonreducing and reducing conditions. It binds to triadin fusion peptides,
      triadin 2, 2a, 3, 3b, and 3b1, but no to triadin 1 or triadin 3b2. The binding to
      triadin 2a is the most prominent. Direct binding between DHPr-644-799 and JFP was
      not seen. These experimental findings indicate that triadin contains an extensive
      cytoplasmic domain that binds to the domain of DHPr which is considered critical
      for signal transmission during skeletal muscle excitation-contraction sampling.

PMID- 7578102
TI  - Disulfide bonds, N-glycosylation and transmembrane topology of skeletal muscle
      triadin.
AB  - Native triadin is a disulfide linked homopolymer of variable subunit number. Two
      monoclonal antibodies (mAbs), AE8.91 and GE4.90, recognize cytoplasmic regions of
      triadin between amino acids 110 and 163 and at the C-terminal 34 amino acids,
      respectively. Triadin in intact triads is largely unaffected by trypsin, while
      triads whose membrane has been disrupted by hypotonicity or by treatment with the
      detergent Triton X-100 yield both soluble and membrane bound fragments. Soluble
      fragments monitored by mAb GE4.90 appear to be formed sequentially during the
      course of proteolysis at 28, 16, 10 and 7 kDa in the presence of mercaptoethanol.
      Higher molecular weight bands are observed under nonreducing conditions. A two
      dimensional electrophoresis immunoblot (first nonreducing; second reducing) of
      the soluble fragments developed with mAb GE4.90 shows the presence of several
      bands which can be interpreted as containing a dimer formed by a combination of
      any two of the fragments of 16, 10, or 7 kDa present in the digest. MAb AE8.91
      does not detect these fragments. This observation indicates that one of the
      intermolecular disulfide bonds is formed between the identical domains of two
      triadin molecules at cysteine 671. Immunoblots performed with and without
      mercaptoethanol of the insoluble fragments using mAb AE8.91 indicate the presence
      of a dimer formed between identical domains of two triadin intermolecular
      disulfide linkage at cysteine 270. The glycosidase endo F/N-glycosidase F changed
      the mobility of intact triadin in TC/triads and its proteolytic fragments
      detected by mAb GE4.90.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578103
TI  - Membrane topology of helices VII and XI in the lactose permease of Escherichia
      coli studied by lacY-phoA fusion analysis and site-directed spectroscopy.
AB  - The use of lactose permease-alkaline phosphatase fusions (lacY-phoA) demonstrates
      that the lactose permease of Escherichia coli contains 12 transmembrane domains
      and that approximately half of a transmembrane domain is required to translocate
      alkaline phosphatase to the periplasmic surface of the membrane [Calamia, J., &
      Manoil, C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4937-4941]. We have now used
      fusion analysis in combination with site-directed spectroscopy to examine more
      precisely the topology of putative helices VII and XI which contain the
      interacting residues Asp237 and Lys358, respectively. For this purpose, alkaline
      phosphatase was fused to alternate amino acid residues in transmembrane domains
      VII and XI. A sharp increase in alkaline phosphatase activity is observed as the
      fusion junction proceeds from Try228 to Ile230 in helix VII and from Phe354 to
      Phe356 in helix XI, suggesting that these residues approximate the middle of the
      corresponding transmembrane helices. Analysis of fluorescence quenching of the
      pyrene-labeled single-Cys mutants Asp237 --> Cys or Lys358 --> Cys, as well as
      measurement of collision frequencies between freely diffusing paramagnetic probes
      and a nitroxide spin-label at these sites, also indicates that Asp237 and also
      Asp240, which interacts with Lys319 (helix X), are located in transmembrane
      domains. However, Asp237 and Asp240 are accessible both from the aqueous phase
      and from within the membrane. The results provide more direct evidence that the
      three residues are located within transmembrane helices and suggest that Asp237
      and Asp240 are either located near the periplasmic surface of the membrane or
      exposed within a solvent-filled cleft in the permease.

PMID- 7578104
TI  - Complexes between chaperonin GroEL and the capsid protein of bacteriophage HK97.
AB  - The 42 kDa capsid protein of bacteriophage HK97 requires the GroEL and GroES
      chaperonin proteins of its Escherichia coli host to facilitate correct folding,
      both in vivo and in vitro. In the absence of GroES and ATP, denatured gp5 forms a
      stable complex with the 14 subunit GroEL molecule. We characterized the
      electrophoretic and biochemical properties of this complex. In electrophoresis on
      a native (nondenaturing) gel, the band of the gp5-GroEL complex shifts to a
      slower migrating position relative to uncomplexed GroEL. The results show that
      there is only one subunit of gp5 bound to each GroEL 14-mer and that the shift in
      band position is due primarily to a change in the overall charge of the complex
      relative to uncomplexed GroEL, and not to a change in size or shape. GroEL forms
      similar complexes with proteolytic fragments of gp5, with a series of sequence
      duplication derivatives of gp5, and with other proteins. Electrophoretic
      examination of these complexes shows that a band shift occurs with proteins
      larger than 31-33 kDa but not with smaller proteins. For those proteins that
      cause a band shift upon complex formation, the magnitude of the shift is
      correlated with the predicted if the charge of the complex were simply the sum of
      the charge of GroEL and the charge of the substrate protein. We suggest that
      binding of a substrate protein to GroEL is accompanied by a net binding of
      solution cations to the complex, but only in the case of proteins above a minimum
      size of 31-33 kDa. The gp5-GroEL complex is in an association/dissociation
      equilibrium, with a binding constant measured in the range of 11-17 microM-1.

PMID- 7578105
TI  - The single-ring Thermoanaerobacter brockii chaperonin 60 (Tbr-EL7) dimerizes to
      Tbr-EL14.Tbr-ES7 under protein folding conditions.
AB  - Chaperone proteins assist in the folding of some newly synthesized proteins and
      inhibit protein aggregation. The Thermoanaerobacter brockii chaperonin proteins
      (Tbr-EL and Tbr-ES) have recently been purified and characterized [Truscott,
      W.N., Hoj, P. B., & Scopes, R. K. (1994) Eur. J. Biochem. 222, 277-284]; Tbr-EL
      was a single seven-membered toroid, unlike most GroELs which exist as double
      toroids. Using high-resolution gel filtration chromatography, we have resolved
      the purified Tbr-EL into single ringed (Tbr-EL7) and double ringed (Tbr-EL14)
      species. The latter contained tightly bound Tbr-ES co-chaperonin (Tbr-EL14.Tbr
      ES7). In the presence of Mg.ATP and either Escherichia coli GroES (Eco-ES) or Tbr
      ES (i.e., under protein folding conditions), the isolated Tbr-EL7 rapidly
      dimerized to the Tbr-EL14.Eco-ES7 or Tbr-EL14.Tbr-ES7 complexes. The doubly
      toroidal species thus formed contained > or = 6 molecules tightly bound ADP and
      one GroES7 and are similar to the asymmetric chaperonin complex isolated from
      Thermus thermophilus [Taguch, H., Konishi, J., Ishii, N., & Yoshida, M. (1991) J.
      Biol. Chem. 266, 22411-22418]. The isolated Tbr-EL7 and Tbr-EL14.Tbr-ES7
      hydrolyzed ATP at approximate to 2 and 1 min-1, respectively. Addition of a molar
      excess of Eco-ES7 to the isolated Tbr-EL7 reduced the ATPase activity to 1 min-1,
      consistent with the formation of Tbr-EL14.Eco-ES7. Eco-ES7 failed to inhibit the
      Tbr-El14.Tbr-ES7 complex. The isolated Tbr-EL14.Tbr-ES7 complex did not support
      the folding of Rubisco under nonpermissive conditions. Only when the complex was
      supplemental with additional GroES was folding of Rubisco observed; i.e., one
      molar equivalent of GroES was not sufficient for folding. Both Tbr-EL7 and Tbr
      EL14.Tbr-ES7 bound on unfolded [35S] Rhodospirillum rubrum Rubisco per mole
      particle. In contrast, Eco-EL14 bound 2 mol of protein per mole particle,
      consistent with each toroid having a peptide binding site. Eco-EL14.Eco-ES7
      complex only bound one unfolded protein, thus GroES binding blocks one GroEL
      peptide binding site. Addition of Eco-ES7 to a Eco-EL14.Rubisco2 complex did not
      result in the displacement of one molecule of Rubisco but in the formation of a
      ternary Eco-EL14.Rubisco2.Eco-ES7 complex.

PMID- 7578106
TI  - Recombinant human liver medium-chain acyl-CoA dehydrogenase: purification,
      characterization, and the mechanism of interactions with functionally diverse C8
      CoA molecules.
AB  - We offer a large scale purification procedure for the recombinant human liver
      medium-chain acyl-CoA dehydrogenase (HMCAD). This procedure routinely yield 100
      150 mg of homogeneous preparation of the enzyme from 80 L of the Escherichia coli
      host cells. A comparative investigation of kinetic properties of the human liver
      and pig kidney enzymes revealed that, except for a few minor differences, both of
      these enzymes are nearly identical. We undertook detailed kinetic and
      thermodynamic investigations for the interaction of HMCAD-FAD with three C8-CoA
      molecules (viz., octanoyl-CoA, 2-octenoyl-CoA, and 2-octynoyl-CoA), which differ
      with respect to the extent of unsaturation of the alpha-beta carbon center;
      octanoyl-CoA and 2-octenoyl-CoA serve as the substrate and product of the enzyme,
      respectively, whereas 2-octynoyl-CoA is known to inactivate the enzyme. Our
      experimental results demonstrate that all three C8-CoA molecules first interact
      with HMCAD-FAD to form corresponding Michaelis complexes, followed by two
      subsequent isomerization reactions. The latter accompany either subtle changes in
      the electronic structures of the individual components (in case of 2-octenoyl-CoA
      and 2-octynoyl-CoA ligands), or a near-complete reduction of the enzyme-bound
      flavin (in case of octanoyl-CoA). The rate and equilibrium constants intrinsic to
      the above microscopic steps exhibit marked similarity with different C8-CoA
      molecules. However, the electronic structural changes accompanying the 2-octynoyl
      CoA-dependent inactivation of enzyme is 3-4 orders of magnitude slower than the
      above isomerization reactions. Hence, the octanoyl-CoA-dependent reductive half
      reaction and the 2-octynoyl-CoA-dependent covalent modification of the enzyme
      occur during entirely different microscopic steps. Arguments are presented that
      the origin of the above difference lies in the protein conformation-dependent
      orientation of Glu-376 in the vicinity of the C8-CoA binding site.

PMID- 7578107
TI  - Analysis of the pH dependence of the neonatal Fc receptor/immunoglobulin G
      interaction using antibody and receptor variants.
AB  - The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) from
      ingested milk in the gut (pH 6.0-6.5) and delivers it to the bloodstream of the
      newborn (pH 7.0-7.5). A soluble version of FcRn reproduces the physiological pH
      dependent interaction with IgG, showing high-affinity binding at pH 6.0-6.5 but
      weak or no binding at pH 7.0-7.5. We have studied the pH dependence of the
      FcRn/IgG interaction using a surface plasmon resonance assay to measure kinetic
      and equilibrium constants. We show that the affinity of FcRn for IgG is reduced
      about 2 orders of magnitude as the pH is raised from 6.0 to 7.0. A hill put
      analysis suggests that several titrating residues participate in the pH-dependent
      affinity transition. Histidine side chains are likely candidate for residues that
      titrate between pH 6.0 and 7.0, and previous biochemical and structural work
      identified several histidines on the Fc portion of IgG that are located at the
      FcRn binding site. Using mutant IgG molecules and IgG subtype variants that
      differ in the number of histidines at the IgG/FcRn interface, we demonstrate that
      IgG histidines located at the junction between the CH2 and CH3 domains (residues
      310 and 433) contribute to the pH-dependent affinity transition. Experiments with
      a mutant FcRn molecule show that two histidines on the FcRn heavy chain (residues
      250 and 251) also contribute to the pH dependence of the FcRn/IgG interaction.
      There results are interpreted using the crystal structures of FcRn and an FcRn/Fc
      complex.

PMID- 7578108
TI  - A trimeric subdomain of the simian immunodeficiency virus envelope glycoprotein.
AB  - Previous attempts to define the oligomeric state of the HIV and SIV envelope
      glycoproteins have yielded conflicting results. We have produced in Escherichia
      coli a recombinant model for the ectodomain of the SIV envelope protein gp41 and
      have identified a small, trimeric subdomain by proteolytic digestion of this gp41
      fragment. The subdomain assembles from two peptide fragments, spanning residues
      28-80 (N28-80) and residues 107-149 (C107-149) of SIV gp41. Each of these
      peptides contains a 4,3-hydrophobic repeat, the hallmark of coiled-coil
      sequences. Upon mixing, the peptides form a highly helical, trimeric complex
      [3(N+C)] that resists proteolysis and has a melting temperature (Tm) above 90
      degrees C in physiological buffer. The N- and C-terminal fragments are
      antiparallel to each other in the complex, as judged by the observation that
      digestion of a variant recombinant protein truncated at the amino terminus yields
      a C-terminal fragment shortened at its carboxy terminus. The N28-80 peptide
      contains more positions within the heptad repeat than C107-149 that are
      predominantly hydrophobic, suggesting that N28-80 is buried in the interior of
      the complex. We propose that the complex consists of a parallel, trimeric coiled
      coil of the N-terminal peptide, encircled by three C-terminal peptide helices
      arranged in an antiparallel fashion, and that this complex forms a core within
      the gp41 extracellular domain.

PMID- 7578109
TI  - A general method for mapping tertiary contacts between amino acid residues in
      membrane-embedded proteins.
AB  - A general method for mapping tertiary interactions in membrane proteins using the
      visual pigment rhodopsin as a model is presented. In this approach, the protein
      is first assembled from two separately expressed gene fragments encoding
      nonoverlapping segments of the full-length polypeptide. Cys residues are then
      introduced into each of the two fragments such that juxtaposed residues are able
      to form disulfide cross-links in the protein either spontaneously or with the
      assistance of a Cu(2+)-(phenanthroline)3 oxidant. The cross-linked polypeptides
      are identified from a characteristic mobility shift on sodium dodecyl sulfate
      (SDS) gels as detected by Western blot analysis where the covalently bound
      heterodimer migrates with a mobility essentially identical to that of the native,
      full-length protein. Three different split rhodopsin mutants were prepared: one
      with a split in the loop connecting helices 3 and 4 (the 3/4 loop), one with a
      split in the 4/5 loop, and one with a split in the 5/6 loop. Each of these
      proteins when purified from transfected COS cells bound 11-cis-retinal, had a
      native absorption maximum at 500 nm, and activated transducin in a light
      dependent manner. The cross-linking assay was tested with the rhodopsin mutant
      split in the 5/6 loop using the rho-1D4 antibody (which recognizes the carboxy
      terminal eight amino acids of rhodopsin) to detect the proteins on Western blots
      of SDS gels. Cys residues were substituted for Val-204 in the amino terminal
      fragment and Phe-276 in the carboxy terminal fragment of the rhodopsin mutant
      because Schwartz and co-workers [Elling et al.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578111
TI  - Crystal structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from
      Leishmania mexicana: implications for structure-based drug design and a new
      position for the inorganic phosphate binding site.
AB  - The structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from
      the trypanosomatid parasite Leishmania mexicana has been determined by X-ray
      crystallography. The protein crystallizes in space group P2(1)2(1)2(1) with unit
      cell parameters a = 99.0 A, b = 126.5 A, and c = 138.9 A. There is one 156,000 Da
      protein tetramer per asymmetric unit. The model of the protein with bound NAD+s
      and phosphates has been refined against 86% complete data from 10.0 to 2.8 A to a
      crystallographic Rfactor of 0.198. Density modification by noncrystallographic
      symmetry averaging was used during model building. The final model of the L.
      mexicana GAPDH tetramer shows small deviations of less than 0.5 degrees from
      ideal 222 molecular symmetry. The structure of L. mexicana GAPDH is very similar
      to that of glycosomal GAPDH from the related trypanosomatid Trypanosoma brucei. A
      significant structural difference between L. mexicana GAPDH and most previously
      determined GAPDH structures occurs in a loop region located at the active site.
      This unusual loop conformation in L. mexicana GAPDH occludes the inorganic
      phosphate binding site which has been seen in previous GAPDH structures. A new
      inorganic phosphate position is observed in the L. mexicana GAPDH structure.
      Model building studies indicate that this new anion binding site is well situated
      for nucleophilic attack of the inorganic phosphate on the thioester intermediate
      in the GAPDH-catalyzed reaction. Since crystals of L. mexicana GAPDH can be grown
      reproducibly and diffract much better than those of T. brucei GAPDH, L. mexicana
      GAPDH will be used as a basis for structure-based drug design targeted against
      trypanosomatid GAPDHs.

PMID- 7578110
TI  - Formation of a porphyrin pi-cation radical in the fluoride complex of horseradish
      peroxidase.
AB  - Horseradish peroxidase (HRP) was oxidized by IrCl6(2-) to a mixture of compounds
      I and II, the rate of oxidation and the ratio of the mixture being greatly
      affected by pH (Hayashi & Yamazaki, 1979). Oxidation of HRP by IrCl6(2-) in the
      presence of fluoride was significantly accelerated. This resulted in the
      formation of a new compound which is a ferric fluoride complex containing a
      porphyrin pi-cation radical. The spectrum of the new compound showed a decreased
      absorption band in the Soret region and a broad band at 570 nm; which was
      converted to that of the original ferric fluoride complex by addition of
      ascorbate or hydroquinone. Addition of cyanide slowed down the oxidation of HRP
      by IrCl6(2-), and the oxidation product was the same as that obtained in the
      absence of cyanide. Compound I was formed when H2O2 was added to HRP in the
      presence of fluoride or cyanide. The one-electron reduction potential (Eo') of
      the oxidized HRP-fluoride complex was measured at several pH values, the Eo'
      value at pH 7 being 861 +/- 4 mV. The ratio of delta Eo' to delta pH was 49 mV/pH
      unit.

PMID- 7578112
TI  - Identification of the active sites of human and schistosomal hypoxanthine-guanine
      phosphoribosyltransferases by GMP-2',3'-dialdehyde affinity labeling.
AB  - Labeling of human and schistosomal hypoxanthine-guanine
      phosphoribosyltransferases (HGPRTases) with GMP-2',3'-dialdehyde (ox-GMP) results
      in nearly complete inactivation of the enzymes. Digestion of the [3H]ox-GMP
      modified HGPRTases with trypsin followed by high-performance liquid
      chromatographic fractionation, partial amino acid sequencing, and mass spectral
      analysis of the labeled peptides revealed that four peptides from each of the two
      HGPRTases were labeled with ox-GMP. The conclusion from these studies indicates
      that two segments of the human enzyme protein, Ser 4-Arg 47 and Ser 91-Arg 100,
      and one region in the schistosomal enzyme, Gly 95-Lys 133, were labeled by ox
      GMP. Since the ox-GMP labeling of human HGPRTase was effectively blocked by
      either GMP or PRibPP, whereas that of schistosomal HGPRTase was inhibited only by
      GMP [Kanaaneh, J., Craig, S. P., III, & Wang, C. C. (1994) Eur. J. Biochem. 223,
      595-601], the two labeled peptides in human enzyme may be involved in binding to
      both GMP and PRibPP while the one peptide in schistosomal enzyme may be
      implicated only in GMP binding. We have also confirmed a previous observation
      [Keough, D. T., Emmerson, B. T., & de Jersey, J. (1991) Biochim. Biophys. Acta
      1096, 95-100] that carboxymethylation of Cys 22 in the human HGPRTase by
      iodoacetate was inhibited by PRibPP. We also demonstrated that the
      carboxymethylation of Cys 25 in schistosomal HGPRTase by iodoacetate was
      specifically blocked by PRibPP. Apparently, the N-terminal regions in both
      enzymes are involved in PRibPP binding. The fact that ox-GMP labels the N
      terminal region in human enzyme but not in schistosomal enzyme and that PRibPP
      protects against ox-GMP labeling in human enzyme but not in schistosomal enzyme
      both suggest that the amino-terminal PRibPP-binding site may be in close
      proximity to the GMP-binding site in human HGPRTase but not in schistosomal
      HGPRTase. This clear distinction between the active sites of human and
      schistosomal HGPRTases could be further exploited for potential opportunities for
      antischistosomal chemotherapy.

PMID- 7578113
TI  - Solution structure of the MutT enzyme, a nucleoside triphosphate
      pyrophosphohydrolase.
AB  - The MutT enzyme (129 residues) catalyzes the hydrolysis of normal and mutagenic
      nucleoside triphosphates, such as 8-oxo-dGTP, by substitution at the rarely
      attacked beta-P, to yield NMP and pyrophosphate. Previous heteronuclear NMR
      studies of MutT have shown the secondary structure to consist of a five-stranded
      mixed beta-sheet connected by the loop I-alpha-helix I--loop II motif, by two
      tight turns, and by loop III, and terminated by loop IV--alpha-helix II
      [Abeygunawardana et al. (1993) Biochemistry 32, 13071-13080; Weber et al. (1993)
      Biochemistry 32, 13081-13087). Complete side-chain assignments of 1H and 13C
      resonances have now been made by 3D C(CO)NH and HCCH-TOCSY experiments. A total
      of 1461 interproton proximities (11 per residue), obtained by 3D 15N-resolved
      NOESY-HSQC and 3D 13C-resolved NOESY-HSQC spectra, including 372 long-range NOEs,
      as well as 65 dihedral angle (phi) restraints and 34 backbone hydrogen bond
      restraints were used to determine the tertiary structure of MutT by distance
      geometry, simulated annealing, and energy minimization with the program X-PLOR.
      The structure is globular and compact with the parallel portion of the beta-sheet
      sandwiched between the two alpha-helices, forming an alpha+beta fold. The
      essential divalent cation has previously been shown to bind near residues Gly-37,
      Gly-38, Lys-39, and Glu-57, and nucleotides have been shown to bind near residues
      Leu-54 and Val-58 by NMR relaxation methods [Frick et al. (1995) Biochemistry 34,
      5577-5586].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578114
TI  - How allosteric effectors can bind to the same protein residue and produce
      opposite shifts in the allosteric equilibrium.
AB  - Monoaldehyde allosteric effectors of hemoglobin were designed, using molecular
      modeling software (GRID), to form a Schiff base adduct with the Val 1 alpha N
      terminal nitrogens and interact via a salt bridge with Arg 141 alpha of the
      opposite subunit. The designed molecules were synthesized if not available. It
      was envisioned that the molecules, which are aldehyde acids, would produce a high
      affinity hemoglobin with potential interest as antisickling agents similar to
      other aldehyde acids reported earlier. X-ray crystallographic analysis indicated
      that the aldehyde acids did bind as modeled de novo in symmetry-related pairs to
      the alpha subunit N-terminal nitrogens. However, oxygen equilibrium curves run on
      solutions obtained from T- (tense) state hemoglobin crystals of reacted effector
      molecules produced low-affinity hemoglobins. The shift in the allosteric
      equilibrium was opposite to that expected. We conclude that the observed shift in
      allosteric equilibrium was due to the acid group on the monoaldehyde aromatic
      ring that forms a salt bridge with the guanidinium ion of Arg 141 alpha on the
      opposite subunit. This added constraint to the T-state structure that ties two
      subunits across the molecular symmetry axis shifts the equilibrium further toward
      the T-state. We tested this idea by comparing aldehydes that form Schiff base
      interactions with the same Val 1 alpha residues but do not interact across the
      dimer subunit symmetry axis (a new one in this study with no acid group and
      others that have had determined crystal structures). The latter aldehydes shift
      the allosteric equilibrium toward the R-state. A hypothesis to predict the
      direction in shift of the allosteric equilibrium is made and indicates that it is
      not exclusively where the molecule binds but how it interacts with the protein to
      stabilize or destabilize the T- (tense) allosteric state.

PMID- 7578115
TI  - Bisaldehyde allosteric effectors as molecular ratchets and probes.
AB  - Four new series of monoaldehyde bisacids and bisaldehyde bisacids with varying
      chain lengths have been synthesized and evaluated as allosteric effectors of
      hemoglobin. Molecular modeling, oxygen equilibrium, and crystallographic studies
      were combined for structure/function studies. Crystallographic analyses of the
      bisaldehydes reveal that Schiff base interaction occurred exclusively between Val
      1 alpha and Lys 99 alpha of the opposite alpha chain even though the two terminal
      Val 1 alpha nitrogens are ideally spaced to also form cross-links. The reason for
      the observed mode of binding appears to be the influence of chain direction set
      by key substitutions on the bisaldehyde molecule. Even longer chain derivatives
      that could overcome the direction set by the key functional groups bind in the
      same manner. These studies support the general conclusion that long flexible
      molecules prefer to bind along cavity walls, like double-sided molecular sticky
      tape, rather than span large open spaces with few chances for interaction. The
      cross-linked bisaldehydes bind at the same site when incubated under both
      allosteric states and exhibit reduced cooperativity with a significant decrease
      in oxygen affinity. The chain length acts as a molecular ratchet and dictates the
      degree of allosteric effect observed. The tighter the cross-link, the greater the
      constraint on the tense- (T-) state and the stronger the allosteric effect that
      is produced. The monoaldehyde bisacids bind in the same fashion with Schiff base
      formation at Val 1 alpha while the acid that replaces the second aldehyde moiety
      forms a salt bridge with Lys 99 alpha of the opposite subunit. This class of
      molecules has weaker allosteric effector activity as would be expected with
      replacement of one covalent bond by a salt bridge. The importance of Lys 99 alpha
      on the allosteric equilibrium is confirmed.

PMID- 7578116
TI  - Sequence-selective DNA recognition and photocleavage: a comparison of enantiomers
      of Rh(en)2phi3+.
AB  - The recognition and photoinduced cleavage of DNA by the enantiomers of
      bis(ethylenediamine)-(9,10-phenanthrenequinone diimine)Rh(III) [Rh(en)2phi3+]
      have been characterized and the basis for enantioselective differences
      delineated. Rh(en)2phi3+ isomers bind strongly to DNA via intercalation and, upon
      photoactivation with near-UV light, produce direct strand cleavage. On the basis
      of product analysis, the photoinduced DNA cleavage appears to proceed by a
      mechanism consistent with that observed for the parent Rh(phen)2phi3+, involving
      direct abstraction of the 3'-hydrogen atom of the deoxyribose by the activated,
      intercalated phi. Quantitative photocleavage titrations indicate tight binding by
      both enantiomers to the DNA duplex. For delta-Rh(en)2phi3+, DNA site affinities
      range from 0.3 x 10(6) to 8.0 x 10(6) M-1, and a distinct preference for GC sites
      is evident. lambda-Rh(en)2phi3+ is found to be sequence neutral with an average
      site affinity of 2 x 10(6) M-1. The basis for sequence selectivity of the
      enantiomers has been examined through comparison of photocleavage patterns to
      those of several phi complexes of rhodium(III) containing or lacking axial
      amines; those complexes containing the axial amines are found to target GC sites.
      DNA photocleavage studies on oligonucleotides containing the modified bases O6
      methylguanine, 7-deazaguanine, and deoxyuracil have been utilized to determine
      points of interaction on the DNA helix. These results establish binding by both
      complexes in the major groove of DNA. Differences in site recognition between
      enantiomers are attributed to the different hydrogen bonding and van der Waals
      contacts available in the major groove for the ancillary ethylenediamine ligands
      which differ in disposition in the two isomers.

PMID- 7578117
TI  - Structural examination of enantioselective intercalation: 1H NMR of Rh(en)2phi3+
      isomers bound to d(GTGCAC)2.
AB  - The enantioselective recognition of d(GTGCAC)2 by delta- and lambda-Rh(en)2phi3+
      (en = ethylenediamine; phi = 9,10-phenanthrenequinone diimine) has been examined
      in a series of one-dimensional (1D) and two-dimensional (2D) 500 MHz 1H NMR
      experiments both to extend our understanding of the basis for the
      enantioselective DNA binding and to gain structural information concerning
      intercalation by the octahedral metal complexes. delta-Rh(en)2phi3+ forms a
      symmetric 1:1 complex with d(GTGCAC)2, and the metal complex is in slow exchange
      with the oligodeoxynucleotide bound form at 295 K. The strong upfield shifts of
      the phi ligand's aromatic protons (0.6-1.3 ppm) are consistent with full
      intercalation of the phi ligand into the DNA base stack. 2D-NOESY experiments
      reveal a loss in internucleotide connectivity between G3 and C4 bases, while new
      NOE cross peaks are observed between the phi ligand and the G3 deoxyribose sugar.
      In contrast to binding by delta-Rh(en)2phi3+, the 1:1 lambda-Rh(en)2phi(3+)
      d(GTGCAC)2 complex shows much broader resonances, and both metal complex and DNA
      protons appear to be in the intermediate exchange regime. The loss of C2 symmetry
      in the 1:1 complex is consistent with binding by lambda-Rh(en)2phi3+ at the T2G3
      step. Although the enantiomeric metal complexes display different sequence
      selectivities and exchange characteristics, lambda- and delta-Rh(en)2phi3+
      interact with the oligonucleotide duplex in a fundamentally similar manner,
      through the full intercalation of the phi ligand. Upfield movements in chemical
      shifts of phi protons are nearly identical for the two enantiomers, and both
      lambda- and delta-Rh(en)2phi3+ stabilize the duplex to melting by 5-10 degrees
      C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578118
TI  - Exploring the role of the solvent in the denaturation of a protein: a molecular
      dynamics study of the DNA binding domain of the 434 repressor.
AB  - Molecular dynamics simulations of the DNA binding domain of 434 repressor are
      presented which aim at unraveling the role of solvent in protein denaturation.
      Four altered solvent models, each mimicking various possible aspects of the
      addition of a denaturant to the aqueous solvent, were used in the simulations to
      analyze their effects on the stability of the protein. The solvent was altered by
      selectively changing the Coulombic interaction between water and protein atoms
      and between different water molecules. The use of a modified solvent model has
      the advantage of mimicking the presence of denaturant without having denaturant
      molecules present in the simulation, which would require much longer simulations.
      In these simulations, only an increase in the solvent-protein Coulombic
      interaction causes initiation of protein unfolding in a manner consistent with
      NMR data. The altered solvent thus provides a model of a denaturing environment
      for studying protein unfolding.

PMID- 7578119
TI  - Utility of a novel spin-labeled nucleotide in investigation of the substrate and
      effector sites of phosphoribulokinase.
AB  - The activated spin-label 3-(2-bromoacetamido)proxyl modifies the sulfur atom of
      phosphorothioate-containing AMP, ADP, and ATP analogs in a facile reaction that
      produces a new series of spin-labeled nucleotides. One of these products,
      adenosine 5'-O-(S-acetamidoproxyl 3-thiotriphosphate) (ATP gamma SAP), has been
      evaluated as a structural probe for Rhodobacter sphaeroides phosphoribulokinase
      (PRK). When incubated with affinity-purified enzyme that contains tightly bound
      substrate ATP, ATP gamma SAP binds noncooperatively to the allosteric site (n =
      1; KD = 8 microM). Probe bound in this site is displaced (K1/2 = 100 microM) by
      the allosteric effector, NADH, at concentrations comparable to those required for
      enzyme activation (Ka = 133 microM). In the presence of NADH, when PRK's
      substrate site is vacant, ATP gamma SAP binds in a cooperative mode (Hill
      coefficient approximately 2.9; KD = 20 microM). In the absence of NADH, ATP gamma
      SAP mimics ATP by exhibiting nonequilibrium binding to PRK. The observations with
      phosphoribulokinase, together with the straightforward nature of the methodology
      documented for synthesis and isolation of this class of spin-labeled nucleotides,
      suggest that these analogs have potentially wide application as structural
      probes.

PMID- 7578120
TI  - Mechanistic studies of the methyltransferase from Clostridium thermoaceticum:
      origin of the pH dependence of the methyl group transfer from
      methyltetrahydrofolate to the corrinoid/iron-sulfur protein.
AB  - A methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase (MeTr)
      from Clostridium thermoaceticum catalyzes the transfer of the N5 methyl group
      from (6S)-methyltetrahydrofolate (CH3-H4folate) to the cobalt center of a
      corrinoid/iron-sulfur protein (C/Fe-SP). The methylcobamide product is the first
      in a series of enzyme-bound organometallic intermediates in the acetyl-CoA
      pathway of anaerobic CO2 fixation. The mechanisms of the forward and reverse
      reactions with CH3-H4folate and either the C/Fe-SP or vitamin B12 as substrates
      were studied by steady-state and pre-steady-state kinetics. This ability to
      effectively utilize free cobalamin as well as the C/Fe-SP in the transmethylation
      appears to explain why [14C]methylcobyric acid was found as a product of labeling
      C. thermoaceticum cells with 14CO2 [Ljungdahl, L. G., Irion, E., & Wood, H. G.
      (1965) Biochemistry 4, 2771-2780]. Stopped-flow experiments indicate that the
      Co(I)-C/Fe-SP performs a direct SN2 displacement of the methyl group of CH3
      H4folate to form H4folate and methyl-Co(III). The pre-steady-state rate constants
      in the forward and reverse reactions increased as the pH was lowered (pKa
      approximately 5.5). Similar pH profiles were obtained by steady-state kinetics.
      The kcat/Km values for the C/Fe-SP and CH3-H4folate in the forward direction and
      for the methylated C/Fe-SP and H4folate in the reverse direction increased as the
      pH was lowered (pKa approximately 5.3). A different pH profile was obtained with
      free cobalamin as the substrate; the kcat/Km for CH3-H4folate and cobalamin
      (forward reaction) increased (pKa approximately 7.0) and the kcat/Km for H4folate
      and methylcobalamin (reverse reaction) decreased (pKa approximately 5.3) as the
      pH was lowered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578121
TI  - Tryptophan 250 on the alpha subunit plays an important role in flavin and
      aldehyde binding to bacterial luciferase. Effects of W-->Y mutations on catalytic
      function.
AB  - Bacterial luciferase is a heterodimer (alpha beta) that catalyzes the oxidation
      of FMNH2 and a fatty aldehyde, resulting in light emission. To explore the nature
      of the flavin binding site with respect to the role of tryptophan residues, the
      catalytic and binding properties of single-point mutants of Xenorhabdus
      luminescens luciferase with one of the eight tryptophans converted to a tyrosine
      residue were investigated by luminescence and fluorescence measurements.
      Conversion of tryptophans 194 and 250 on the alpha subunit to tyrosine had
      relatively large effects on the properties of luciferase with only minor changes
      in the properties on mutation of the other four tryptophans on alpha and the two
      on the beta subunit. Mutation of alpha W250 decreased the binding to FMNH2, FMN,
      aldehyde, and fatty acid, causing major changes in luminescence emission and
      decay. The results are consistent with alpha W250 interacting with flavin which
      in turn affects aldehyde binding. Mutation of alpha W194 did not affect the
      interaction with flavin or aldehyde but did change the relative rate of decay of
      light emission with aldehydes of different chain lengths as well as the
      activation energy for this process. Moreover, these results provide evidence for
      alpha W250, and to a lesser extent alpha W194, being in contact with the
      isoalloxazine ring of flavin, a proposal that has been recently made based on a
      model with flavin bound to the alpha subunit and anchored at a binding site for
      the phosphate moiety of FMN(H2) identified in the crystal structure of Vibrio
      harveyi luciferase [Fisher, A. J. Raushel, F. M., Baldwin, T. O., & Rayment, I.
      (1995) Biochemistry 34, 6581-6586].

PMID- 7578122
TI  - Inhibition of nitric oxide synthase activity by Zn2+ ion.
AB  - We have found neural nitric oxide synthase (nNOS) activity to be completely and
      reversibly inhibited by Zn2+ ion with an apparent Ki of 30 microM. Zn2+ blocks
      NADPH-dependent reduction of heme iron in nNOS and also blocks the calmodulin
      dependent superoxide-mediated cytochrome c reductase activity exhibited by nNOS.
      However, Zn2+ ion has no apparent effect on the calmodulin-independent direct
      reduction of cytochrome c by nNOS. Zn2+ ion induces perturbation difference
      spectra in nNOS characterized by the appearance of a peak at approximately 430 nm
      and a trough at approximately 395 nm, with an apparent spectral binding constant
      of 50 microM. These spectral changes are consistent with a Zn(2+)-dependent
      change in the spin-state equilibrium of the heme iron in nNOS. The spectral
      binding constant for L-arginine binding to nNOS (approximately 1.5 microM) is not
      significantly affected by the presence of 50 microM Zn2+, indicating that Zn(2+)
      dependent inhibition of nNOS activity is not due to interference with substrate
      binding. The estimated maximal change in nNOS absorbance at approximately 418 nm
      caused by the L-arginine-dependent conversion of the ferric heme iron from
      hexacoordinate low-spin to pentacoordinate high-spin is increased by 50% in the
      presence of 50 microM Zn2+, which reflects the increased initial amount of low
      spin ferric heme iron present. These data indicate that Zn(2+)-dependent
      inhibition of nNOS activity is due to binding of Zn2+ to the hemoprotein domain
      in the enzyme and that inhibition is associated with perturbations in the
      environment of the heme iron that appear to block its ability to mediate oxygen
      reduction.

PMID- 7578123
TI  - Effects of a naturally occurring compatible osmolyte on the internal dynamics of
      ribonuclease A.
AB  - Osmolytes are small organic solutes accumulated intracellularly by many organisms
      as they adapt to environmental stresses. Compatible osmolytes, a functional class
      of osmolytes, increase protein stability while having little or no effect on
      protein function. To investigate the interrelationships between protein
      stability, function, and internal dynamics, a hydrogen exchange (HX) quench
      method was established and used to study the effects of sucrose (a typical
      compatible osmolyte) on the structural fluctuations of ribonuclease A. It was
      found that the HX rates of the amide protons with intermediate rates are not
      affected by 1 M sucrose, but the slow-exchanging amide protons exchange even
      slower in 1 M sucrose. The protection factors of the slow-exchanging protons fall
      into a comparatively narrow range while those of the intermediate-exchanging
      protons vary widely. In agreement with the two-process model [Woodward, C.K., &
      Hilton, B. D. (1980) Biophys. J. 32, 561-575], we conclude that for those slow
      exchanging amide protons, the exchange occurs mainly from the compact unfolded
      state ensemble of the protein. The internal dynamics leading to slow exchange
      involve exposure of large protein surface areas, similar to that which occurs
      upon the unfolding of protein. Because sucrose opposes such an increase in
      protein surface area exposure, both the slow HX rates and the protein stability
      are affected by sucrose. For those amide protons with fast and intermediate HX
      rates, the exchange occurs mainly from the native state ensemble of the protein.
      The internal dynamics involved in the exchange are localized without much surface
      area change, and functionally important structural fluctuations are likely to
      occur within this dynamic range.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578124
TI  - Evidence for a two-state transition in the folding process of the activation
      domain of human procarboxypeptidase A2.
AB  - The activation domain of human procarboxypeptidase A2 (ADA2h), a globular open
      sandwich alpha + beta domain with 80 residues and no disulfide bridges, has been
      studied by thermodynamic and kinetic analysis. Equilibrium denaturation by urea
      or temperature is fully reversible at pH 7.0 and fits to a two-state transition.
      The Gibbs energy of unfolding extrapolated to null concentration of chemical
      denaturant, delta GH2O, at pH 7.0 and 298 K, is calculated to be 17.0 +/- 1 kJ
      mol-1, which is within experimental error of the value determined by differential
      scanning calorimetry, 15.1 +/- 2 kJ mol-1. Kinetics of unfolding and refolding
      followed by fluorescence do not show the presence of any kinetic intermediate
      accumulating in the folding reaction. A value for delta GH2O of 17.9 +/- 0.7 kJ
      mol-1 can be extrapolated from the kinetic data. All these data indicate that the
      folding pathway of this domain is consistent with a two-state model (with the
      exception of the cis-Pro intermediates). More importantly, the analysis of this
      and several other small domains or proteins supports the hypothesis that stable
      kinetic folding intermediates are not necessary for a protein to fold. There
      seems to be a relationship between the size of a protein and the presence of
      stable kinetic intermediates. Globular proteins with less than 80 residues and no
      disulfide bonds follow a two-state transition, while proteins larger than 100
      residues present stable kinetic folding intermediates.

PMID- 7578125
TI  - Effects of tyrphostins, protein kinase inhibitors, on human immunodeficiency
      virus type 1 integrase.
AB  - Efficient replication of HIV-1 requires establishment of the proviral state,
      i.e., the integration of a DNA copy of the viral genome, synthesized by reverse
      transcriptase, into a chromosome of the host cell. Integration is catalyzed by
      the viral integrase protein. We have previously reported that phenolic moieties
      in compounds such as napthoquinones, flavones, caffeic acid phenethyl ester
      (CAPE), and curcumin confer inhibitory activity against HIV-1 integrase. We have
      extended these findings by examining the effects of tryphostins, tyrosine kinase
      inhibitors. The catalytic activities of HIV-1 integrase and the formation of
      enzyme-DNA complexes using photocross-linking were examined. Both steps of the
      integration reaction, 3'-processing and strand transfer, were inhibited by
      tyrphostins at micromolar concentrations. The DNA binding activity of integrase
      was inhibited at higher concentrations of tryphostins. Disintegration, an
      apparent reversal of the strand transfer reaction, catalyzed by an integrase
      mutant lacking the N-terminal zinc finger and C-terminal DNA binding domains is
      also inhibited by tyrphostins, indicating that the binding site for these
      compounds resides in the central catalytic core of HIV-1 integrase. Binding of
      tyrphostins at or near the integrase catalytic site was also suggested by
      experiments showing a global inhibition of the choice of attacking nucleophile in
      the 3'-processing reaction. None of the tryphostins tested inhibited eukaryotic
      topoisomerase I, even at 100 microM, suggesting selectivity for integrase
      inhibition. Molecular-modeling studies have revealed that, after energy
      minimization, several tyrphostins may adopt folded conformations. The similarity
      of the tyrphostin family to other families of inhibitors is discussed.
      Tyrphostins may provide lead compounds for development of novel antiviral agents
      for the treatment of acquired immunodeficiency syndrome based upon inhibition of
      HIV-1 integrase.

PMID- 7578127
TI  - Pathways of formation of glycoxidation products during glycation of collagen.
AB  - Glycoxidation products (GOPs), such as N epsilon-(carboxymethyl)lysine (CML) and
      pentosidine, are formed during reaction of glucose with protein under oxidative
      conditions in vitro. It is uncertain whether these GOPs are derived from
      oxidation of Amadori adducts on protein or from oxidation of glucose or
      intermediates formed prior to the Amadori rearrangement. To address this
      question, we reacted collagen with 250 mM glucose in 200 mM phosphate buffer, pH
      7.4, under antioxidative conditions, yielding a protein rich in Amadori adducts,
      but with only traces of GOPs. This "preglycated" collagen was then exposed to
      [13C6]glucose under oxidative conditions, producing both natural and [13C2]-CML.
      At 200 mM phosphate buffer, [13C2]-CML was the major product, even at low (5 mM)
      [13C6]glucose concentration, indicating a limited role for Amadori compounds in
      formation of CML in high phosphate. The relative yields of natural and [13C2]-CML
      varied with phosphate concentration, becoming similar at more physiological (10
      mM) phosphate. We conclude that during glycation of proteins at high phosphate
      concentrations in vitro, GOPs are formed primarily by oxidation of free glucose
      or rapidly-formed intermediates preceding the Amadori rearrangement, such as
      carbinolamine or Schiff base adducts. In contrast, at lower phosphate and glucose
      concentrations in vivo, the Amadori adduct may be the more significant precursor
      of GOPs. The fact that glycoxidation reactions proceed by multiple routes must be
      considered in the development of therapeutic approaches for inhibiting the
      Maillard reaction in diabetes.

PMID- 7578126
TI  - Inhibition of trypsin with active-site-directed enzyme-activated nitrosoamide
      substrates.
AB  - A series of active-site-directed enzyme-activated nitrosoamide inhibitors of
      trypsin has been designed, synthesized, and tested. The inhibitors contain an N
      nitrosoamide group that can generate an alkylating agent and a positively charged
      ammonium ion group at the end of an aliphatic carbon chain that provides
      specificity. The half-lives of inhibition under normal conditions were 0.6 to 2
      min for compounds in series 1. One of the compounds, N-(4-amino-1-butyl)-N
      nitrosobenzamide (1b), is a very efficient inhibitor; its partition ratio,
      k2/kinact, is zero suggesting that it may be a useful titrant for trypsin and
      related enzymes. The extent of inhibition is substantially decreased by the
      competitive inhibitor benzamidine, indicating that the inhibitors were operating
      in the active site. Two modes of inhibition were noted: reversible and
      irreversible. The N-nitrosoamide inhibitors bind to the trypsin binding pocket
      guided by the primary specificity. They then acylate the enzyme (at Ser-195),
      producing a leaving group that generates diazonium ions (or) carbocations in the
      active site; these react with a proximal carboxylic acid side chain of the enzyme
      to form a carboxylic acid ester, presumably that of Asp-194. If primary amino
      groups are present on the alkyl group, the ester (13C NMR delta 67.2 ppm for
      R1COO13CH2-(CH2)nNH2) rearranges into the amide form (13C NMR delta 62.9 ppm for
      R1CONH(CH2)n13CH2OH) through an O-->N acyl migration; an irreversibly inhibited
      enzyme results. A model based on the orientation of the site-specific group of N
      (4-amino-1-butyl)-N-nitroso-N'-isobutyryl-D-alaninamide (D2a) and its L antipode
      in the active site of trypsin is proposed to explain the preferential inhibition
      of trypsin by the D-isomer. Analysis of the structure--inhibition relationship
      revealed four factors that determine the inhibition modes of the inhibitors: 1,
      length of the alkyl group; 2, stability of the acyl-enzyme; 3, the option O--N
      acyl migration; and 4, chirality.

PMID- 7578128
TI  - Structure of both the ligand- and lipid-dependent channel-inactive states of the
      nicotinic acetylcholine receptor probed by FTIR spectroscopy and hydrogen
      exchange.
AB  - FTIR spectra have been recorded both as a function of time and after prolonged
      exposure to 2H2O buffer in order to study the structural changes that lead to
      both the ligand- and lipid-dependent channel-inactive states of the nicotinic
      acetylcholine receptor (nAChR). The hydrogen/deuterium exchange spectra provide
      insight into both the overall rates and extent of peptide 1H/2H exchange and the
      individual rates and extent to which peptide hydrogens in alpha-helix and beta
      sheet conformations exchange for deuterium. The spectra are also sensitive to the
      conformation of the polypeptide backbone and thus the secondary structure of the
      nAChR. The various spectral features monitored in the presence and absence of
      carbamylcholine and tetracaine are essentially identical, indicating that there
      are no large net changes in secondary structure in the channel-inactive
      desensitized state. The various spectral features monitored for the nAChR
      reconstituted into lipid membranes either with or without cholesterol are very
      similar, indicating that cholesterol is not a major structural regulator of the
      nAChR. However, in the absence of both cholesterol and anionic lipids, there is a
      slightly enhanced rate of exchange of alpha-helical peptide hydrogens for
      deuterium that occurs as a result of either an increase in nAChR dynamics or an
      increase in the accessibility of transmembrane peptide hydrogens to 2H2O. The
      latter may simply be due to an increase in the "fluidity" and thus permeability
      of the lipid bilayers to aqueous solvent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578129
TI  - Solution conformation of the extracellular domain of the human tumor necrosis
      factor receptor probed by Raman and UV-resonance Raman spectroscopy: structural
      effects of an engineered PEG linker.
AB  - The solution structure of the Escherichia coli-expressed extracellular domain,
      residues 12-172, of the human 55 kDa type I tumor necrosis factor receptor (TNFR)
      has been probed by Raman (514.5 nm) and ultraviolet-resonance Raman (244 nm)
      excitations. The Raman spectra have been collected from both the free TNFR domain
      and an engineered "dumbbell-like" derivative, consisting of two mutant receptor
      moieties linked by a 20 kDa polyethylene glycol (PEG) tether. The results
      demonstrate a TNFR secondary structure which is rich in beta-sheet and deficient
      in alpha-helix, consistent with the reported X-ray crystal structure of
      baculovirus expressed receptor complexed with factor beta [Banner, D. W., D'Arcy,
      A., Janes, W., Gentz, R., Schoenfeld, H.-J., Broger, C., Loetscher, H., &
      Lesslauer, W. (1993) Cell 73, 431-445]. Conversely, the solution structure of
      TNFR differs from the crystal structure in its distribution of disulfide rotamers
      and in the orientation of its unique indole side chain (tryptophan-107). These
      differences are attributed, respectively, to N-terminal truncation and factor
      binding in the TNFR crystal structure. The tryptophan configuration, which is
      easily monitored in both Raman and UVRR spectra, is proposed as a potential
      signal of receptor/factor recognition and binding. Application of the Raman
      probes to the engineered TNFR dumbbell, which is of interest as a potential
      therapeutic, shows that TNFR moieties of the dumbbell exhibit secondary
      structures and side chain environments which are indistinguishable from those of
      the native, wild-type moiety. The results suggest that the PEGylated dumbbell may
      function as an effective TNFR drug delivery system without the consequence of a
      deleterious antigenic response.

PMID- 7578130
TI  - Endogenous K+/H+ exchange activity in the Sf9 insect cell line.
AB  - The fluorescent pH indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein
      (BCECF) was used to investigate changes in the intracellular pH (pHi) of
      individual Sf9 cells in response to changes in the composition of the external
      medium. Under standard conditions, the resting pHi was 0.2-0.3 unit lower than
      the extracellular pH (6.5). The extracellular concentration of K+ had a major
      influence on pHi. Removal of K+ from the medium resulted in a rapid but
      reversible acidification of the cells. The buffer capacity of the cells was a U
      shaped function of pHi with a minimum at about pHi = 6.2. In the presence of K+,
      a change in the pH of the medium was followed by an equivalent change in pHi. In
      its absence, however, changes in the external pH had little effect on the pH of
      the cells. Following removal of K+ from the medium, the cells realkalinized at an
      initial rate which increased with increasing concentration of added K+. This
      cation was about 30 times more effective in promoting realkalinization of the
      cells than Li+ Na+, Rb+, and Cs+. The apparent Km for K(+)-dependent H+ efflux
      was about 12 mM and was slightly modulated by extracellular pH. These results
      strongly suggest that, in Sf9 cells, a K+/H+ antiporter plays a key role in the
      movement of protons across the cell membrane.

PMID- 7578131
TI  - Cooperativity and binding in the mechanism of cytosolic phospholipase A2.
AB  - Cytosolic phospholipase A2 (cPLA2) hydrolyzes the sn-2 ester of phospholipids and
      is believed to be responsible for the receptor-regulated release of arachidonic
      acid from phospholipid pools. The enzyme was assayed using vesicles containing
      arachidonate-containing phospholipid substrate, such as 1-palmitoyl-2
      arachidonoylphosphatidylcholine (PAPC) or 1-stearoyl-2
      arachidonoylphosphatidylinositol (SAPI), dispersed within vesicles of 1,2
      dimyristoylphosphatidylmethanol (DMPM). We report here that the enzyme shows an
      apparent cooperative effect with respect to the mole fraction of arachidonate
      containing phospholipids within these covesicles. The data can be fit to a
      modified Hill equation yielding Hill coefficients, n, of 2-3. This effect is
      unusual in that it is dependent on the nature of the sn-2 ester as opposed to the
      phosphoglycerol head group. This cooperativity is independent of both the
      concentration of glycerol, which greatly increases enzyme activity and stability,
      and the concentration of calcium, which facilitates the fusion of the covesicles.
      Surprisingly, 1-palmitoyl-2-arachidonoylphosphatidylethanolamine (PAPE) does not
      show the same cooperative effect, although the rate at which it is hydrolyzed is
      much greater when PAPC is present. Moreover, PAPE has a dissociation constant
      from the active site (KD* = 0.7 mol %) which is comparable to that of PAPC and
      SAPI (KD* values of 0.3 and 0.3 mol %, respectively). These results are
      consistent with the presence of an allosteric site that, when occupied, induces a
      change in the enzyme which facilitates enzymatic hydrolysis. If so, PAPC and
      SAPI, but not PAPE, must be able to bind to this allosteric site. Alternatively,
      this effect may result from changes in the physical nature of the bilayer which
      result upon increasing the bilayer concentration of arachidonate-containing
      phospholipids. This previously unobserved effect may represent another mechanism
      by which cells can regulate the activity of cPLA2.

PMID- 7578132
TI  - Expression and purification of the light chain of botulinum neurotoxin A: a
      single mutation abolishes its cleavage of SNAP-25 and neurotoxicity after
      reconstitution with the heavy chain.
AB  - Botulinum neurotoxin type A (BoNT/A) selectively and irreversibly inhibits
      acetylcholine release from peripheral nerve endings. While the toxin's heavy (H)
      chain contributes to neuronal binding and internalization, its light (L) chain is
      a Zn(2+)-dependent endoprotease that intracellularly cleaves synaptosomal
      associated protein of M(r) = 25 kDa (SNAP-25). For research and clinical
      exploitation of this uniquely-acting neurotoxin, recombinant wild-type L chain
      was produced together with a mutant in which His227 in the Zn(2+)-binding motif
      was substituted by Tyr. The PCR-amplified wild-type and mutant L chain genes were
      cloned, fused to the gene for maltose-binding protein, and expressed at high
      levels in Escherichia coli. The soluble fusion proteins were purified using
      amylose affinity chromatography, and, after factor Xa cleavage, the free L chains
      were isolated. The wild-type was shown to proteolyze SNAP-25 at a rate
      approaching that of the native chain while the mutant was inactive.
      Reconstitution of the pure wild-type L chain with native homogeneous H chain
      yielded a disulfide-linked dichain form that inhibited neuromuscular transmission
      in vitro and produced the symptoms of botulism in vivo. After reconstitution with
      the H chain, the Tyr227 mutant L chain failed to show any neuroparalytic activity
      in either of these assays. This methodology allows, for the first time, routine
      preparation of recombinant forms of the L chain that are needed to decipher the
      molecular details of its interaction with substrate and, thereby, assist the
      design of effective inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578133
TI  - The actin-binding protein hisactophilin binds in vitro to partially charged
      membranes and mediates actin coupling to membranes.
AB  - The interaction of the actin-binding protein hisactophilin from Dictyostelium
      discoideum amoebae to partially charged lipid membranes composed of mixtures of L
      alpha-dimyristoylphosphatidylcholine (DMPC) with L-alpha
      dimyristoylphosphatidylglycerol (DMPG) and L-alpha-phosphatidylinositol 4,5
      bisphosphate (PIP2) is studied by film balance experiments, microfluorescence,
      and lateral diffusion measurements at low ionic strengths (approximately 20 mM).
      Excess surface concentrations and adhesion energies of the protein are evaluated
      by the application of Gibbs law of surface excess as a function of charged lipid
      content. Protein expressed in E. coli lacking a myristic acid chain (EC-HIS) and
      natural protein with a fatty acid (DIC-HIS) isolated from Dictyostelium cells are
      compared. For mixtures of DMPG and DMPC, protein binding leads to an increase in
      lateral pressure of the monolayer (at constant area) and causes strong lipid
      immobilization pointing to partial penetration of the protein into the lipid
      layer. The natural protein causes a much stronger immobilization than does EC
      HIS. For a given bulk concentration, the adsorbed protein/lipid molar ratio
      increases with the molar fraction chi PG of charged lipid but saturates at about
      50 mol% of DMPG. Natural hisactophilin (DIC-HIS) binding to PIP2-containing
      monolayers is purely electrostatic at low bulk concentration cb, and protein
      penetration dominates only at cb > 68 nM. Fluorescence experiments demonstrate
      that the natural protein (DIC-HIS) can mediate the binding of monomeric actin or
      very small oligomers to membranes, showing that the adsorbed protein remains
      functional. In contrast, the recombinant hisactophilin (EC-HIS) can mediate only
      the membrane coupling of larger actin structures.

PMID- 7578134
TI  - Conversion of cytochrome b562 to c-type cytochromes.
AB  - Cytochrome b562 from the periplasm of Escherichia coli is the only member of a
      family of cytochromes sharing the 4-alpha-helical bundle structural motif that
      does not have a covalently bound heme. We have introduced cysteine residues into
      the amino acid sequence of cytochrome b562 in positions homologous to those found
      in the other members of the family, generating the ubiquitous heme-binding
      peptide (-C-X-Y-C-H-) found in virtually all c-type cytochromes. The resulting
      single-cysteine-containing mutants, R98C and Y101C, together with the double
      mutant combining both of these mutations have been expressed into the periplasm
      of E. coli. The apo- and holoprotein products of each mutation have been
      isolated, and all the mutants produce multiple species with covalently attached
      heme. Results from ion exchange chromatograph, optical spectroscopy, SDS gel
      electrophoresis, and electrospray mass spectrometry identified those species that
      appear to be cytochrome b562 holoprotein with thioether covalent linkages to the
      heme as the only difference in chemical composition between them and the wild
      type protein. Results from 1H-NMR experiments prove the existence of the expected
      c-type covalent bonds in each of these proteins and show that the structure of
      the heme pocket is not significantly perturbed by the covalent modification(s).
      These proteins all have perturbed optical spectra, compared with those of the
      wild-type protein, that are consistent with the modifications but are still
      characteristic of six-coordinate, low-spin cytochromes with Met-His ligation to
      the heme iron in both oxidation states.

PMID- 7578135
TI  - Iron(II) oxidation by H chain ferritin: evidence from site-directed mutagenesis
      that a transient blue species is formed at the dinuclear iron center.
AB  - The iron storage molecule, ferritin, consists of an iron core surrounded by a
      shell of 24 protein subunits, which, in mammals, are of two types, H and L. Prior
      to storage of iron as a hydrous ferric oxide within the protein shell, Fe(II) is
      catalytically oxidized at dinuclear centers within H chains. When 48 Fe(II)
      atoms/molecule were added to 1 microM recombinant human H chain apoferritin (apo
      HuHF), in 0.1 M Mes (pH 6.5), oxidation was 80% complete within about 0.2 s while
      99% of the Fe(II) was oxidized within 10 s. A broad visible absorption band (400
      800 nm, with a maximum at 650 nm) appeared during the fast phase of Fe(II)
      oxidation. It reached a plateau at 0.2-0.3 s and then declined while Fe(II)
      oxidation proceeded to completion and absorbance in the near-UV (300-400 nm)
      increased. The transient visible species was not observed when Tyr-34 was
      replaced by phenylalanine or when other conserved amino acids at the ferroxidase
      centers were substituted by residues which are unable to bind iron or which alter
      the charge balance. When a second increment of 48 iron atoms was added, 10 min
      after the first, the visible absorbance was absent and the rate of oxidation
      slower. Restoration of full oxidative activity took over 24 h. The data indicate
      that the fast oxidation of Fe(II) by apo-HuHF and the transient visible
      absorbance associated with it are due to Fe(II) oxidation at the ferroxidase
      centers.

PMID- 7578136
TI  - Pigment content of D1-D2-cytochrome b559 reaction center preparations after
      removal of CP47 contamination: an immunological study.
AB  - Isolated D1-D2-cytochrome b559 photosystem II reaction center preparations with
      pigment stoichiometry higher than 4 chlorophylls per 2 pheophytins can be
      contaminated with CP47 proximal antenna complex. Reaction center prepared by a
      modification of the Nanba-Satoh procedure and containing about 6 chlorophylls per
      2 pheophytins showed immuno-cross-reactivity when probed with a monoclonal
      antibody raised against the CP47 polypeptide. Furthermore, they could be
      fractionated successfully by Superose-12 sieve chromatography into two different
      populations. The first few fractions off the column contained a more definitive
      435 nm shoulder corresponding to increased chlorophyll content, and showed strong
      immuno-cross-reactivity with the CP47 antibody. The peak fractions off the column
      displayed a less prominent 435 nm shoulder, and did not cross-react with the
      antibody. Moreover, when a 6-chlorophyll preparation was mixed with Sepharose
      beads coupled to CP47 antibody, the eluted material corresponded to a preparation
      of about 4 chlorophylls per 2 pheophytins and did not show any cross-reaction
      with the antibody against CP47. The amount of CP47 protein in the 6-chlorophyll
      preparation as quantitated using Coomassie Blue staining or from gel blots was
      sufficient to account for most of the extra 2 chlorophylls. We conclude that D1
      D2-cytochrome b559 preparations containing more than 4 chlorophylls per 2
      pheophytins can be contaminated with small amounts of CP47-D1-D2-Cyt b559 complex
      and that native photosystem II reaction centers contain 4 core chlorophylls per 2
      pheophytins.

PMID- 7578138
TI  - The asymmetry of P+ in bacterial reaction centers revealed by circular dichroism
      spectroscopy.
AB  - The circular dichroism anisotropy, (AL-AR)/A, has been measured for the far-red
      absorption band of P+ in reaction centers of two purple bacteria
      (Rhodopseudomonas viridis and Rhodobacter sphaerides) and one green sulfur
      bacterium (Chlorobium tepidum). The anisotropy values for P960+ (Rps. virdis) at
      1310 nm was found to be +(13 +/- 2) x 10(-4). The corresponding for P870+ (Rb.
      sphaeroides) at 1250 nm was +(11 +/- 1) x 10(-4), but for P840+ (C. tepdium) at
      1160 nm the value was negative: -(27 +/- 2) x 10(-4). These results show that the
      configuration of the special pair in P840 is significantly different from the
      configuration in P870 and P960.

PMID- 7578137
TI  - Structure and kinetics of formation of catechol complexes of ferric soybean
      lipoxygenase-1.
AB  - Ferric soybean lipoxygenase forms stable complexes with 4-substituted catechols.
      The structure of the complex between the enzyme and 3,4-dihydroxybenzonitrile has
      been studied by resonance Raman, electron paramagnetic resonance, visible, and X
      ray spectroscopies. It is a bidentate iron-catecholate complex with at least one
      water ligand. The kinetics of formation of complexes between lipoxygenase and 3,4
      dihydroxybenzonitrile and 3,4-dihydroxyacetophenone have been studied by stopped
      flow spectroscopy. The data are consistent with two kinetically distinct,
      reversible steps. The pH dependence of the first step suggests that the substrate
      for the reaction is the catechol monoanion. When these results are combined,
      plausible mechanisms for the complexation reaction are suggested.

PMID- 7578139
TI  - Role of PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 1. PufX
      is required for efficient light-driven electron transfer and photophosphorylation
      under anaerobic conditions.
AB  - The pufX gene is essential for photoheterotrophic growth of the purple bacterium
      Rhodobacter sphaeroides. In order to analyze the molecular function of the PufX
      membrane protein, we constructed a chromosomal pufX deletion mutant and
      phenotypically compared it to a pufX+ control strain and to two suppressor
      mutants which are able to grow photosynthetically in the absence of pufX. Using
      this genetic background, we confirmed that PufX is required for
      photoheterotrophic growth under anaerobic conditions, although all components of
      the photosynthetic apparatus were present in similar amounts in all strains
      investigated. We show that the deletion of PufX is not lethal for illuminated
      pufX- cells, suggesting that PufX is required for photosynthetic cell division.
      Since chromatophores isolated from the pufX- mutant were found to be unsealed
      vesicles, the role of PufX in photosynthetic energy transduction was studied in
      vivo. We show that PufX is essential for light-induced ATP synthesis
      (photophosphorylation) in anaerobically incubated cells. Measurements of
      absorption changes induced by a single turnover flash demonstrated that PufX is
      not required for electron flow through the reaction center and the cytochrome bc1
      complex under anaerobic conditions. During prolonged illumination, however, PufX
      is essential for the generation of a sufficiently large membrane potential to
      allow photosynthetic growth. These in vivo results demonstrate that under
      anaerobic conditions PufX plays an essential role in facilitating effective
      interaction of the components of the photosynthetic apparatus.

PMID- 7578141
TI  - CP-MAS 13C-NMR dipolar correlation spectroscopy of 13C-enriched chlorosomes and
      isolated bacteriochlorophyll c aggregates of Chlorobium tepidum: the self
      organization of pigments is the main structural feature of chlorosomes.
AB  - Magic angle spinning (MAS) NMR dipolar correlation spectroscopy was applied for
      the first time to a biologically intact system, the light-harvesting chlorosomes
      of the green photosynthetic bacterium Chlorobium tepidum. The MAS spectra provide
      evidence that the self-organization of many thousands of bacteriochlorophyll c
      (BChl c) molecules is the predominant structural feature of the chlorosome. 13C
      Enriched chlorosomes were prepared from nonuniformly labeled cultures grown with
      NaH13CO3 as the main carbon source and from a uniformly 13C-labeled culture grown
      with NaH13CO3 as the sole carbon source. For the nonuniformly labeled samples,
      the positions of the chlorin macrocycle originating from C-4 and C-5 of 5
      aminolevulinic acid contained > 95% 13C while the remaining positions, which
      could have originated also from unlabeled acetate, were labeled to approximately
      60% with 13C. The 1-D and 2-D MAS data of the labeled chlorosomes, when compared
      with data on the isolated labeled BChl c aggregated in n-hexane, show that the
      major component of the MAS signals in the chlorosomes is from BChl c, and only
      minor signal contributions arise from lipids and proteins. The 13C MAS signals of
      the BChl c aggregates were fully assigned by MAS 2-D dipolar correlation
      spectroscopy, using data on monomeric BChl c in CDCl3/CD3OD as reference. The
      2(1)-, 3-, 3(2-), 5-, 12(1)-, 13-, and 13(1)-carbons are shifted by 2.5 ppm or
      more upfield with respect to the solution data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578140
TI  - Role of the PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 2.
      PufX is required for efficient ubiquinone/ubiquinol exchange between the reaction
      center QB site and the cytochrome bc1 complex.
AB  - The PufX membrane protein is essential for photosynthetic growth of Rhodobacter
      sphaeroides because it is required for multiple-turnover electron transfer under
      anaerobic conditions [see accompanying article; Barz, W. P., Francia, F.,
      Venturoli, G., Melandri, B. A., Vermeglio, A., & Oesterhelt, D. (1995)
      Biochemistry 34, 15235-15247]. In order to understand the molecular role of PufX,
      light-induced absorption spectroscopy was performed using a pufX- mutant, a pufX+
      strain, and two suppressor mutants. We show that the reaction center (RC)
      requires PufX for its functionality under different redox conditions than the
      cytochrome bc1 complex: When the kinetics of flash-induced reduction of
      cytochrome b561 were monitored in chromatophores, we observed a requirement of
      PufX for turnover of the cytochrome bc1 complex only at high redox potential (Eh
      > 140 mV), suggesting a function of PufX in lateral ubiquinol transfer from the
      RC. In contrast, PufX is required for multiple turnover of the RC only under
      reducing conditions: When the Q pool was partially oxidized in vivo using oxygen
      or electron acceptors like dimethyl sulfoxide or trimethylamine N-oxide, the
      deletion of PufX had no effect on light-driven electron flow through the RC.
      Flash train experiments under anaerobic in vivo conditions revealed that RC
      photochemistry does not depend on PufX for the first two flash excitations.
      Following the third and subsequent flashes, however, efficient charge separation
      requires PufX, indicating an important role of PufX for fast Q/QH2 exchange at
      the QB site of the RC. We show that the Q/QH2 exchange rate is reduced
      approximately 500-fold by the deletion of PufX when the Q pool is nearly
      completely reduced, demonstrating an essential role of PufX for the access of
      ubiquinone to the QB site. The fast ubiquinone/ubiquinol exchange is partially
      restored by suppressor mutations altering the macromolecular antenna structure.
      These results suggest an indirect role of PufX in structurally organizing a
      functional photosynthetic apparatus.

PMID- 7578142
TI  - A thermal broadening analysis of absorption spectra of the D1/D2/cytochrome b-559
      complex in terms of Gaussian decomposition sub-bands.
AB  - Absorption spectra of the isolated D1/D2/cytochrome b-559 complex have been
      measured in the temperature range 80-300 K. All spectra were analyzed in terms of
      a linear combination of Gaussian bands and the thermal broadening data
      interpreted in terms of a model in which the spectrum of each pigment site is
      broadened by (a) a homogeneous component due to linear electron-phonon coupling
      to a low-frequency protein vibration and (b) an inhomogeneous component
      associated with stochastic fluctuations at each pigment site. In order to obtain
      a numerically adequate description of the absorption spectra, a minimum number of
      five sub-bands is required. Further refinement of this sub-band description was
      achieved by taking into account published data from hole burning and absorption
      difference spectroscopy. In this way, both a six sub-band description and a seven
      sub-band description were generated. In arriving at the seven sub-band
      description, the original five sub-band wavelength positions were essentially
      unchanged. Thermal broadening analysis of the seven sub-band description yielded
      data which displayed the closest correspondence with the literature observations.
      The wavelength positions of the sub-bands were near 661, 667, 670, and 675 nm,
      with two bands near 680 and 684 nm. The two almost isoenergetic sub-bands near
      680 nm, identified as P680 and pheophytin, have optical reorganization energies
      around 40 and 16 cm-1, respectively. All other sub-bands, identified as accessory
      pigments, have optical reorganization energies close to 16 cm-1.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578143
TI  - Use of fluorescence resonance energy transfer to estimate intramolecular
      distances in the Msx-1 homeodomain.
AB  - We have utilized fluorescence resonance energy transfer (FRET) to investigate the
      spatial proximities of segments in the Msx-1 homeodomain (Msx). This strategy
      makes use of a single, invariant tryptophan (Trp-48) in helix III as the donor
      for FRET. The acceptor molecule, 5-[[[(iodoacetyl)amino]-ethyl]amino]naphthalene
      1-sulfonic acid (AEDANS), was incorporated into Msx at positions 6, 10, or 27
      which are within the N-terminal arm, and helices I and II since these segments
      have been implicated in interactions with helix III. Specific incorporation of
      AEDANS was achieved by using a two-step strategy consisting of site-directed
      mutagenesis for introducing unique cysteine residues at the selected positions
      followed by covalent modification of these cysteine residues with AEDANS. Using
      this approach, we demonstrated energy transfer between Trp-48 and the AEDANS
      labeled cysteines at positions 6, 10, and 27 and estimated the distances between
      the Trp-48 and AEDANS pairs to be 19, 23, and 16 A, respectively. We further
      demonstrated that FRET provides a strategy for detecting subtle alterations in
      protein conformation that result from replacement of specific residues in helix
      III and the N-terminal arm. Together, these findings show that FRET provides a
      useful approach for estimating intramolecular distances and for examining the
      conformation of Msx. Moreover, given the fact that Trp-48 is invariant among all
      homeodomain sequences, we propose that FRET will provide a general approach for
      facilitating comparative analyses of homeodomain conformations.

PMID- 7578145
TI  - Assessment of stability differences in the protein G B1 and B2 domains from
      hydrogen-deuterium exchange: comparison with calorimetric data.
AB  - Hydrogen-deuterium (H-D) exchange experiments have been used to measure exchange
      rates for almost all of the main-chain amide protons (NHs) in the B1 and B2 IgG
      binding domains of protein G. For H-bonded NHs, exchange rates were also measured
      as a function of temperature from 25 to 65 degrees C for B1 and from 25 to 60
      degrees C for B2. A number of NHs exchange by a mechanism consistent with global
      unfolding. For these residues, the free energy required for transient opening of
      a H-bonded NH (delta Gop) from H-D exchange approximates the extrapolated free
      energy of thermal unfolding (delta Gu) from calorimetry in B1 and B2. The
      difference in exchange rates between B1 and B2 for these residues reflects the 1
      kcal mol-1 difference in stability from calorimetry. The more stable B1 domain
      appears to have a slightly larger core of residues which exchange by global
      unfolding than B2. The delta Gop values for slow exchange H-bonded NHs and
      calorimetric delta Gu provide highly complementary information on the delta G
      versus temperature stability profiles of B1 and B2. Furthermore, NH exchange
      rates provide a very sensitive measure of local stability differences between B1
      and B2. In both domains, the beta 2-strand is the least stable of the beta-sheet
      although it is more stable in B1 than B2. The largest local stability differences
      occur at residues Y3 and T18 which exchange 40-fold and 100-fold slower in B1,
      respectively. These residues form a H-bond donor-acceptor pair at one end of the
      beta 1-beta 2 region. Local stability differences are also evident near the beta
      1-beta 2 turn. These stability differences are, at least in part, due to subtle
      differences in hydrophobic packing effects. They are not obvious from inspection
      of the B1 and B2 structures but are manifested as readily measurable changes in
      NH exchange rates for individual residues. Knowledge of these local stability
      differences in the beta 1-beta 2 region provides potential approaches for
      designing new stability mutants in protein G. Most non-H-bonded NHs have exchange
      rates that are < 15 times slower than their intrinsic rates. In marked contrast,
      the NHs of K10, T11, and L12 in the beta 1-beta 2 turn and V21 have exchange
      rates which are five to > or = 24 times faster than their intrinsic rates,
      probably due to local electrostatic effects.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7578144
TI  - Self-association of the molecular chaperone HSC70.
AB  - The self-association properties of the molecular chaperone HSC70 have been
      analyzed by a wide range of biochemical and biophysical techniques. Nondenaturing
      gel electrophoresis and cross-linking studies show the presence of multiple
      species going from monomer to at least trimer. Size-exclusion chromatography
      gives two overlapping peaks, a major one corresponding to species having the
      molecular mass of monomer (70 kDa) and a minor broad one corresponding to species
      with a molecular mass range of 150-300 kDa. Progressive dilution of the protein
      leads to an increase in the size of the monomer peak at the expense of that of
      the oligomeric peak, thus indicating a concentration-dependent chemical
      equilibrium. Sedimentation velocity reveals the presence of three species, whose
      proportions were dependent on concentration, but whose sedimentation
      coefficients, s20,w, of 4.3, 6.6, and 8.5 S did not vary with concentration,
      indicative of a slowly equilibrating system. Sedimentation equilibrium studies
      confirmed these results and showed a dissociation into monomers at low
      concentrations and an association into dimers and trimers at high concentrations.
      The multiple sedimentation equilibrium datasets, obtained at various initial
      loading concentrations as well as different rotor speeds, were fitted to a single
      set of equilibrium constants by a monomer-dimer-trimer association model in which
      the association constants for the monomer-dimer and dimer-trimer equilibrium were
      respectively K1-2 = 1.1 x 10(5) M-1 and K2-3 = 0.9 x 10(5) M-1. Interestingly, an
      isodesmic, indefinite type of association describes the data almost equally well
      with a single constant of 1.2 x 10(5) M-1. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578148
TI  - Kinetic and thermodynamic characterization of the reaction catalyzed by a
      polynucleotide kinase ribozyme.
AB  - We have previously isolated a series of ribozymes with polynucleotide kinase
      activity [Lorsch, J.R., & Szostak, J.W. (1994) Nature 371, 31-36]. In order to
      learn how such newly evolved RNAs effect catalysis, we have determined a number
      of the kinetic and thermodynamic parameters for the reaction catalyzed by one of
      these ribozymes. This ribozyme, a class I polynucleotide kinase, catalyzes the
      transfer of the gamma-(thio)phosphate from ATP(-gamma S) to the 5'-hydroxyl of a
      7-mer oligoribonucleotide. The kcat for the reaction with ATP-gamma S is 0.17 min
      1 with a Km of approximately 3 mM. The Km for the oligoribonucleotide substrate
      5'-HO-GGAACCU-3' is 2 microM, the same as the Kd for this substrate in the
      presence or absence of ATP-gamma S. Neither the binding of substrates nor the
      release of products is the rate-limiting step of the reaction. The binding of
      substrates and release of products appear to occur in a random fashion, with no
      synergy of binding between the ATP(-gamma S) and oligoribonucleotide substrates.
      The ribozyme binds the oligoribonucleotide substrate no more strongly than would
      be expected for the formation of a simple RNA-RNA duplex, suggesting that there
      are no tertiary contacts between the ribozyme and the RNA substrate. The
      oligoribonucleotide substrate binding site has been located, and the sequence
      specificity of the ribozyme could be altered by mutating this binding site. The
      ribozyme is specific for adenosine triphosphate substrates; GTP-gamma S reacts
      approximately 650-fold slower than ATP-gamma S. With ATP as the substrate, the
      Kms remain unchanged, but kcat decreases by a factor of 50, consistent with a
      rate-limiting chemical step occurring through a dissociative transition state.
      The pH independence (from pH 5.5 to 8.5) of kcat/Km and of the rate constant for
      the conversion of the ternary substrate complex into the ternary products complex
      is also consistent with a dissociative phosphoryl transfer mechanism. These
      results suggest that this newly evolved catalyst operates in a relatively simple
      manner, with independent substrate binding sites and without changing the
      mechanism of the underlying chemical reaction.

PMID- 7578147
TI  - Phospholipase A2 engineering. The roles of disulfide bonds in structure,
      conformational stability, and catalytic function.
AB  - Site-directed mutagenesis was used to probe the contribution of each of the seven
      disulfide bonds of bovine pancreatic phospholipase A2 (PLA2, overexpressed in
      Escherichia coli) to the structure, conformational stability, and catalytic
      function of the enzyme. Each of the seven disulfide bonds, C11-C77, C27-C123, C29
      C45, C44-C105, C51-C98, C61-C91, and C84-C96, was deleted separately by changing
      both cysteine (C) residues to alanine (A). The structural properties of the
      mutants were analyzed by 1D and 2D proton NMR, the conformational stability by
      guanidine hydrochloride-induced denaturation, and the catalytic property by
      measuring kinetic parameters toward DC8PC (1,2-dioctanoyl-sn-glycero-3
      phosphocholine) micelles. The results led to the following significant findings:
      (i) All but one (C84A-C96A) mutants have been refolded and purified by use of the
      same procedure for wild-type PLA2. Thus, the disulfide bonds are generally not
      important to the folding pathway of PLA2. (ii) The disulfide bond C11-C77 is most
      important to the conformation and conformational stability of the enzyme since
      deletion of this disulfide bond resulted in greatly perturbed NMR properties and
      in a decrease of 6.2 kcal/mol in conformational stability. However, the C11A-C77A
      mutant displayed little change in catalytic function. (iii) The effects of
      deleting disulfide bonds on the catalytic function of PLA2 are small, except the
      disulfide bond C29-C45 which connects the calcium binding loop with the helix C.
      However, the conformation and conformational stability of the C29A-C45A mutant
      was found to decrease by a factor of 10 or greater. (ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7578149
TI  - A peptide derived from a tissue factor loop region functions as a tissue factor-
      factor VIIa antagonist.
AB  - Tissue factor (TF) is a transmembrane protein that functions in the initiation of
      blood coagulation in vivo. At sites of vascular injury, TF serves as a cell
      surface receptor for the serine protease factor VIIa (FVIIa), forming an enzyme-
      cofactor complex and enhancing the catalytic activity of FVIIa. Tissue factor,
      along with the receptors for alpha- and gamma-interferons, is a member of the
      class 2 cytokine receptor superfamily. Crystallographic analysis demonstrated
      that the extracellular domain of TF consists of two immunoglobulin-like domains
      joined by a linker region. Each domain is comprised of two antiparallel beta
      sheets containing seven conserved beta-strands separated by more variable loop
      regions. Extensive mutagenesis has been performed in order to map the FVIIa
      binding site on TF. Results indicated that the discontinuous binding site for
      FVIIa lies at the domain--domain interface and includes residues from extended
      loops and beta-strands within both the N- and C-terminal domains. Our previous
      study provided evidence that three consecutive residues (D44, W45, K46) within
      the TF loop region between beta-strands C and C' of the N-terminal domain were
      important for interactions with FVIIa. We have presently extended our alanine
      scanning mutagenesis to include the residues within the flanking beta-strands.
      Thirteen sTF mutants were screened for their ability to enhance FVIIa activity.
      Three residues within strand C (Y34, Q37, I38) and two residues within C' (K48,
      Y51) were shown to be important for TF cofactor function.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7578146
TI  - Analysis of i,i+5 and i,i+8 hydrophobic interactions in a helical model peptide
      bearing the hydrophobic staple motif.
AB  - In this work we have analyzed by far-UV circular dichroism the contribution to
      alpha-helix stability of pairwise hydrophobic interactions in the hydrophobic
      staple motif [Munoz et al. (1995) Nat. Struct. Biol. 2, 380-385]. For this, we
      have used a new series of alanine-based model peptides having a capping-box motif
      (Ser-X-X-Glu) and no other charged residues to facilitate the determination of
      the interaction energies with a helix/coil transition algorithm. Our results show
      that the favorable i,i+5 interaction between a hydrophobic residue (Leu, Met,
      Ile, Val, Phe) at position N' (before the N-cap) and a Leu at position N+4
      (inside the helix) contributes up to -1.48 +/- 0.18 kcal/mol to alpha-helix
      stability at 278 and pH 7. More interestingly, the same hydrophobic residues at
      position N' interact favorably with an Ala at position N+4, although the
      interaction is weaker than that with Leu (up to -0.8 +/- 0.14 kcal/mol at 278 K
      and pH 7). To our knowledge, this is the first example in which a strong pairwise
      interaction with Ala is described and suggests that Ala could be less neutral in
      terms of side chain-side chain interactions than normally assumed. We observe a
      strong stereospecificity for the position N' which could be explained based on
      the extreme rigidity imposed by the formation in phase of the hydrophobic staple
      and capping-box motifs, as is seen in the protein structure database. We have
      also investigated the contribution to alpha-helix stability of a geometrically
      feasible i,i+8 hydrophobic interaction between residues N' and N+7.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578150
TI  - Structural alignments of (+)- and (-)-trans-anti-benzo[a]pyrene-dG adducts
      positioned at a DNA template-primer junction.
AB  - The structural features of a chemically modified DNA template strand may promote
      error-prone DNA synthesis during replication. The resulting higher incidence of
      mutations, in turn, can eventually lead to tumor initiation. Structural insights
      into this process can be monitored by studying chemically modified base adducts
      of defined stereochemistry positioned site-specifically at a single strand-
      duplex template--primer junction. We have used a NMR-molecular mechanics approach
      to obtain the solution conformations of the covalent adducts derived from trans
      additions at the [BP]C10 position of the highly tumorigenic (+)-anti
      benzo[a]pyrene diol epoxide [(+)-anti-BPDE] and nontumorigenic (-)-anti-benzo
      [a]pyrene diol epoxide [(-)-anti-BPDE] to the N2 position of guanine [(+) and (-)
      trans-anti-[BP]dG, respectively] in the d(A1-A2-C3-[BP]G4-C5-T6-A7-C8-C9-A10-T11
      C12-C13).d (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer DNA sequence. The
      modified 13-mer strand constitutes the template strand, while the complementary 9
      mer strand constitutes a primer which has been synthesized from the 3'-end of the
      template toward the 5'-end up to the base preceding, but not including, the
      modified guanine. The modified guanine (denoted by [BP]dG4) is positioned at the
      junction site between the single-stranded and duplex segments. Structural
      features of the (+)-trans-anti-[BP]dG 13/9-mer have been determined by
      incorporating proton--proton distances defined by lower and upper bounds deduced
      from NOESY spectra as restraints in molecular mechanics computations in torsion
      angle space. The 3'-side duplex segment retains a minimally perturbed B-DNA
      conformation with all nine base pairs in Watson--Crick hydrogen-bonded
      alignments. Conformational heterogeneity is detected at the single-stranded d(A1
      A2-C3) segment located 5' to the modified (+)-trans-anti-[BP]dG lesion which
      contrasts with an unperturbed alignment of these same residues in the unmodified
      control 13/9-mer. The modified guanine adopts a syn glycosidic torsion angle, is
      displaced into the major groove, and no longer stacks over the adjacent dC5.dG22
      base pair. Such a base displacement is accompanied by stacking of one face of the
      pyrenyl ring with the dC5.dG22 base pair located on the duplex segment proximate
      to the modified guanine, while the other face of BP is exposed to
      solvent.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7578151
TI  - Catalytic activity of the SH2 domain of human pp60c-src; evidence from NMR, mass
      spectrometry, site-directed mutagenesis and kinetic studies for an inherent
      phosphatase activity.
AB  - During solution structural studies it was apparent that the human recombinant
      pp60c-src SH2 domain (srcSH2, residues 144-249) possessed an inherent phosphatase
      (Pase) activity. Complexes of U[13C,15N]srcSH2 with unlabeled Ac-pYEEIE (I) were
      examined using 31P and 1H-detected isotope filtered NMR methods. The presence of
      a high-affinity complex in equimolar solutions of I and U[13C, 15N]-srcSH2 was
      demonstrated by chemical shift perturbations, line broadening, and the
      observation of intermolecular nuclear Overhauser effects from the pY and Ile side
      chain protons of I to protons on amino acid residues present in the binding
      pocket of srcSH2. Solutions containing excess I relative to srcSH2 revealed a
      slow hydrolysis of I to produce Ac-YEEIE and inorganic phosphate. The hydrolysis
      rate determined from NMR and HPLC-electrospray ionization mass spectrometry data
      at 30 degrees C for solutions containing excess I was 0.002-0.003 h-1. srcSH2
      also catalyzed the hydrolysis of p-nitrophenyl phosphate (pNPP). Isoelectric
      focusing gels of a number of mutant srcSH2s demonstrated that this activity
      comigrated with srcSH2. Km, kcat, and kcat/Km were 3.7 +/- 0.4 mM, 3.1 +/- 0.2 x
      10(-2) min-1, and 8.4 +/- 0.4 M-1 min-1, respectively, toward pNPP. The C188A
      mutant of the srcSH2 domain displayed 15% of the activity displayed by wild-type
      srcSH2, demonstrating that this residue is not absolutely required for activity.
      Two additional mutations in the known pY binding site, R178K and R158K, also
      resulted in decreased pNPPase activity, suggesting that the activity resides in
      or near this site. The inhibitor profile and pH dependence suggest that this is a
      novel protein Pase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578152
TI  - Probing the structure of long single-stranded DNA fragments with neocarzinostatin
      chromophore. Extension of the base-catalyzed bulge-specific reaction.
AB  - The base-catalyzed (bc) thiol-independent cleavage reaction of neocarzinostatin
      chromophore (NCS chrom) has been characterized with long single-stranded (ss) DNA
      in order to use this reaction as a selective probe for the tertiary structure of
      naturally occurring ss nucleic acids. The ss circular phi chi 174 phage and
      M13mp18 phage DNAs (approximately 5000 and 7500 bases, respectively) were shown
      to be bc NCS chrom reaction substrates, exhibiting the expected pH dependence.
      The ss DNA fragments (150-450 bases) were cleaved at six major sites; the lesions
      occurred at T-rich non-double-stranded sequences, as predicted from comparison
      with the minimal energy secondary structures. These sites exhibited the expected
      pH and drug: DNA ratio dependence shown to be required for this reaction.
      Optimization of the shortest sequence, which gave the highest cleavage yield,
      identified the minimal sequence requirements for the site (19-mer of the sequence
      3'TACTGAGTCTCCTTTTGTA5', attacked residue in bold). Folding pattern analysis
      predicted that the oligonucleotide contained a two-base bulge at the cleavage
      site; this result was consistent with the observation that removing features
      which destabilize the bulged structure increased the cleavage yield. Furthermore,
      the derived 19-mer was shown to generate maximal amounts of the final drug
      product of the bc DNA cleavage reaction. Reaction of an RNA 339-mer containing
      the same sequence as one of the long ss DNA fragments showed it not to be a
      substrate for the bc reaction, while similar results were obtained for the RNA
      analog of shorter oligodeoxyribonucleotides identified in this and earlier
      studies. Through a combination of thermodynamic and kinetic assays, the observed
      difference in reactivity was shown to be the result of the low binding of the
      cleaving species to RNA.

PMID- 7578153
TI  - Alanine-scanning mutagenesis of human transcript elongation factor TFIIS.
AB  - TFIIS is a transcription elongation factor that binds to RNA polymerase II and
      allows it to transcribe through a variety of transcriptional blockages by
      inducing cleavage near the 3' end of the nascent transcript. Although this
      cleavage reaction plays a key role in the process of reactivation of
      transcription by TFIIS, the exact mechanism by which TFIIS promotes readthrough
      by RNA polymerase II is not completely understood. We therefore undertook a
      systematic mutagenesis of the C-terminal half of TFIIS (delta TFIIS) to evaluate
      the contribution of charged residues in this region to induce transcript cleavage
      and promote readthrough in vitro. Twenty-two delta TFIIS alanine-scanning mutants
      were constructed by substitution of alanine for each amino acid in clusters of
      charged residues in the C-terminal half of HeLa TFIIS. The ability to induce
      transcript cleavage and readthrough of these mutants was tested in vitro using
      RNA polymerase II ternary elongation complexes arrested at a block to elongation.
      This alanine-scanning mutagenesis analysis allowed the identification of regions
      or residues important for the activity of TFIIS. Many of the mutants were reduced
      alike in both cleavage and readthrough activities. However, in several cases
      there was no simple correlation between these activity reductions.

PMID- 7578155
TI  - Moving on: who is on-board?

PMID- 7578154
TI  - tRNA-guanine transglycosylase from Escherichia coli: structure-activity studies
      investigating the role of the aminomethyl substituent of the heterocyclic
      substrate PreQ1.
AB  - A series of 5-substituted 2-aminopyrrolo[2,3-d]pyrimidin-4(3H)-ones have been
      synthesized in order to study the substrate specificity of the tRNA-guanine
      transglycosylase (TGT) from Escherichia coli. A number of these compounds were
      initially examined as inhibitors of radiolabeled guanine incorporation into tRNA
      catalyzed by TGT [Hoops, G. C., Garcia, G. A., & Townsend, L. B. (1992) 204th
      National Meeting of the American Chemical Society, Washington, DC, August 23-28,
      1992, Division of Medicinal Chemistry, Abstract 113]. The kinetic parameters of
      these analogues as substrates in the TGT reaction have been determined by
      monitoring the loss of radiolabeled guanine from 8-[14C]G34-tRNA. This study
      reveals that the tRNA-guanine transglycosylase from E. coli will tolerate a wide
      variety of substituents at the 5-position. The role of the 5-substituent appears
      to be entirely in binding/recognition with no apparent effects upon catalysis. A
      correlation between N7 pKa and Vmax suggests the deprotonation of N7 during the
      reaction, which must occur prior to subsequent glycosidic bond formation, appears
      to be partially rate-determining for the natural substrate. Comparison of the Kis
      of 7-methyl-substituted competitive inhibitors to the Kms of their corresponding
      substrates suggests that some substrates (including preQ1) are kinetically
      "sticky" (i.e., Km is equivalent to Kd) and other substrates have Kms that
      reflect catalytic rates as well as binding.

PMID- 7578156
TI  - Between two worlds: bridging the cultures of child health and adult medicine.

PMID- 7578157
TI  - Global trends of young people with chronic and disabling conditions.

PMID- 7578159
TI  - Transition to adult health care: setting the stage.

PMID- 7578158
TI  - Transition health services for youth with disabilities: a global perspective.

PMID- 7578160
TI  - The primary care provider's role in caring for young people with chronic illness.

PMID- 7578161
TI  - Strategies for health education for adolescent patients: a preliminary
      investigation.
AB  - OBJECTIVE: To determine the effect of unidirectional and bidirectional health
      education strategies on the amount of patient participation in the discourse
      between adolescent patients and physicians. METHODS: Videotapes of medical
      interviews between physician and adolescent patients that had been made in an
      earlier study of the efficacy of a self-report questionnaire were reviewed. An
      inductive method of content analysis from a small sample of videotapes was used
      to develop mutually exclusive categories of health education communication
      strategies from the variety of strategies employed by physicians. Seven different
      strategies were identified and grouped into two categories, unidirectional and
      bidirectional. Thirty videotapes were randomly selected (from the 79 available
      videotapes) and health education segments were identified, categorized, and coded
      for the amount of time the patient and physician spent talking. Paired student's
      t-tests were used to compare the time spent talking by patients and physicians in
      the two health education strategy categories. RESULTS: The patients consisted of
      17 females and 13 males (mean age = 19.3). Two hundred thirty five individual
      health education strategies were identified, of which 183 (78%) were
      unidirectional and 52 (22%) were bidirectional. Physicians spent an average of
      44.4 seconds talking in the unidirectional strategies, and 11.4 seconds in the
      bidirectional strategies (p = 0.0001). Patients spent 10.9 seconds and 26.1
      seconds talking, respectively, in response to these strategies, (p = 0.07). The
      ratio of the time spent talking by patients to physicians was 0.14 for the
      unidirectional strategies and 1.06 for the bidirectional strategies (p = 0.004).
      CONCLUSIONS: Bidirectional health education communication strategies increase the
      amount of participation of adolescent patients in physician-patient discourse
      when compared to unidirectional strategies. The implications of these data for
      health education with adolescent patients are discussed.

PMID- 7578162
TI  - Validity of self-assessment of sexual maturation in adolescent male patients with
      cystic fibrosis.
AB  - PURPOSE: Self-assessment of sexual maturity by healthy male adolescents has been
      found to correlate closely with physician ratings. Data are lacking, however, in
      adolescents with cystic fibrosis (CF), where an altered body image may affect
      self-assessment. Delayed sexual maturation occurs in many patients with CF,
      particularly those with severe disease. We hypothesized that self-assessment of
      sexual maturation by adolescents with CF would agree with physician ratings.
      METHODS: Using Tanner's standard photographs for pubic hair (PH) and genital (G)
      development, we compared self-assessment of sexual maturation to physician rating
      in 34 adolescent male patients with CF and 27 healthy male controls (C). RESULTS:
      The two groups did not differ in age. All subjects were initially examined and
      Tanner-staged by a physician (SRB), and instructed in self-assessment using the
      Tanner photographs; they then performed a self-assessment. Scores by physician
      and subjects were assessed for inter-observer agreement by Kappa analysis. For
      the CF group, 29 of 34 PH assessments and 21 of 34 G assessments demonstrated
      exact inter-observer agreement between physician and subject ratings. The Kappa
      coefficient, kappa, (weighted for the degree of closeness between two observers)
      was 0.946 for PH and 0.840 for G and the C group, kappa was 0.905 for PH and
      0.737 for G. Repeat analysis combining stages 3 and 4 PH and G development
      yielded higher inter-observer agreement in the CF group (33 of 34 PH assessments
      and 26 of 34 G assessments) and in the C group (24 of 27 PH assessments and 18 of
      27 G assessments). CONCLUSIONS: Self-assessment is a valid method to assess
      sexual maturity in clinical evaluation and as a research tool in the study of
      patients with CF.

PMID- 7578163
TI  - Reproductive health in young women with cystic fibrosis: knowledge, behavior and
      attitudes.
AB  - PURPOSE: The improved life-expectancy in cystic fibrosis (CF) results in the fact
      that the majority of affected young women now survive to face the same
      reproductive health decisions as other women, in addition to those that
      specifically relate to CF. The aim of this study was to assess the reproductive
      health knowledge of women with CF, to investigate the range of their reproductive
      health problems, and to review their reproductive health attitudes and behaviors.
      METHODS: Women aged 18 years and over attending CF services in the state of
      Victoria, Australia were invited to complete a reproductive health questionnaire.
      Comparison subjects (n = 76) were enrolled from 2 primary care practices.
      RESULTS: Fifty-five women participated (89%), with a median age of 22 years
      (range 18-50). There was no significant difference in marital status between the
      two groups and a similar proportion were sexually active, yet women with CF were
      less likely to use contraception. A majority of women with CF believed that
      fertility was reduced, and there was poor knowledge of the potentially
      deleterious effect of pregnancy. A relatively high proportion were planning to
      become pregnant in the near future. Twenty-two percent had tried to conceive,
      with a success rate of 67%. CONCLUSIONS: Women with CF are currently lacking
      important information about reproductive health that potentially has a major
      impact on their health and their lives.

PMID- 7578165
TI  - Fellowships in adolescent medicine-1996.

PMID- 7578164
TI  - Concerns and risk behaviors and the association between them among high-school
      students in Jerusalem.
AB  - PURPOSE: To study the distribution, prevalence, determinants, and association
      between the health, social, and environmental concerns and risk behaviors of high
      school students in Jerusalem in order to provide a better basis for preventive
      and health promotion services. METHODS: 1078 tenth grade high school students, 15
      16 years old answered an anonymous questionnaire including, perceived concerns
      and risk behaviors, (e.g., smoking, alcohol, drugs, and sexual activity).
      Concerns were grouped into six domains. RESULTS: The most frequently reported
      concerns related to school, weight, coping with aggression, fatigue, war,
      enlistment into army, and relationships with peers. Girls had more concerns in
      the domains of self-image, anxiety, and relationships with peers (p < .05).
      Adolescents with mothers who had less education had significantly more concerns
      in the domains of anxiety and relationships with peers and adults (p < .05).
      Forty-seven percent engaged in at least one risk behavior (boys 63% and girls
      34%). The Guttman scalogram indicated the following sequence of risk behaviors:
      alcohol, cigarettes, sex, and drugs. There were statistically significant
      associations between concerns and risk behaviors in the domains of anxiety, sex,
      and relationships with adults and peers. CONCLUSION: Many adolescent concerns are
      universal, although the ranking and prevalence may vary based on different
      regional and population characteristics (e.g., in this population a high rate of
      concerns relating to aggression and war were identified). The results support the
      need to develop prevention and health promotion programs relating to the concerns
      and risk behaviors in the school and community, and individual counseling
      programs in primary care settings.

PMID- 7578166
TI  - Cholesterol-lowering therapy after heart transplantation: a 12-month randomized
      trial.
AB  - BACKGROUND: Hypercholesterolemia, a common problem after heart transplantation,
      may be important in the genesis and progression of allograft coronary artery
      disease. The current study was performed to compare the efficacy of gemfibrozil,
      simvastatin, and cholestyramine for cholesterol lowering in heart transplant
      recipients. METHODS: In this prospective 1-year study, 48 heart transplant
      recipients with moderate hypercholesterolemia were randomized to therapy with
      gemfibrozil 600 mg twice daily (n = 17), simvastatin 10 mg daily (n = 13), and
      cholestyramine 4 gm twice daily (n = 18). Detailed lipoprotein analysis was
      performed at baseline and after 3, 6, and 12 months of treatment. RESULTS: Total
      cholesterol and low-density lipoprotein cholesterol were reduced 19% and 29%,
      respectively, after 3 months of simvastatin therapy (p < 0.0001) with a sustained
      reduction in total cholesterol (25%) and low-density lipoprotein cholesterol
      (39%) at 1 year. Gemfibrozil and cholestyramine treatment did not result in a
      reduction in cholesterol levels. Apolipoprotein B levels were reduced by 29% at
      the end of 1 year with simvastatin but not with the other treatments. Serum
      triglyceride levels were reduced significantly by treatment with gemfibrozil (up
      to 36%, p < 0.01) but not by the other treatments. High-density lipoprotein
      cholesterol initially rose in patients treated with simvastatin and gemfibrozil;
      however, this effect did not persist to 12 months. However, the ratio of low
      density lipoprotein/high-density lipoprotein was favorably affected by
      simvastatin, with a 38% reduction by 12 months (p < 0.0001) but not by the other
      treatments. Over the course of 1 year, 14 patients dropped out of the study: four
      from the gemfibrozil arm and ten from the cholestyramine arm. Gastrointestinal
      intolerance was the most common reason for study termination (8 of 14). All
      patients in the simvastatin treatment arm completed 12 months of therapy. No
      biochemical abnormalities resulted from any therapy, and no therapy caused
      significant alteration in cyclosporine blood levels. CONCLUSIONS: Of the three
      therapies studied, simvastatin was found to be the most efficacious and well
      tolerated for cholesterol lowering in patients after heart transplantation.

PMID- 7578168
TI  - Presence of severe intimal thickening by intravascular ultrasonography predicts
      cardiac events in cardiac allograft vasculopathy.
AB  - BACKGROUND: The clinical utility of intimal hyperplasia detected by intravascular
      ultrasonography in predicting cardiac events in heart transplant recipients with
      cardiac allograft vasculopathy has not been previously investigated. METHODS:
      Intravascular ultrasonographic examination of 74 consecutive heart transplant
      recipients, including 62 men and 12 women with a mean age of 51 +/- 10 years
      (range 22 to 68 years), was performed at the time of annual angiography. Two
      groups of study patients were identified: group I consisted of patients with
      minimal, mild, or moderate intimal thickness by intravascular ultrasonography,
      whereas group II patients had severe intimal thickness. RESULTS: Patient
      characteristics were similar in both groups except for higher serum triglycerides
      (220 +/- 95 versus 165 +/- 79 mg/dl), more advanced donor age (28 +/- 11 versus
      23 +/- 6 years) and greater duration of follow-up after transplantation (3.3 +/-
      1.4 versus 1.8 +/- 1.2 years) in group II patients with severe intimal thickening
      (p < 0.01). Cardiac events were defined as the occurrence of sudden death,
      myocardial infarction, or the need for coronary revascularization via
      percutaneous or surgical intervention. One cardiac event occurred in group I
      patients (sudden death), whereas seven events were noted in the group II patients
      (p = 0.006). Cardiac events in the group of patients with severe intimal
      thickening included four patients with sudden cardiac death and three patients
      who underwent percutaneous revascularization procedures involving directional
      coronary atherectomy. Angiograms were normal in 62% of patients who had cardiac
      events. CONCLUSIONS: This study represents one of the first reports that provides
      evidence that severe intimal hyperplasia predicts the development of cardiac
      events even in the presence of a normal coronary angiogram.

PMID- 7578167
TI  - Management of biliary complications after heart transplantation.
AB  - BACKGROUND: Immunosuppression increases the risk of biliary complications in
      heart transplant recipients. METHODS: Patients undergoing heart transplantation
      since 1986 who were at risk for cholelithiasis (n = 60) were retrospectively
      studied. RESULTS: Cholestatic jaundice developed in all patients after the
      operation because of biliary obstruction from cholelithiasis, cyclosporine
      toxicity, Imuran toxicity, or Gilbert's disease. The incidence of cholelithiasis
      or sludge was 42% (n = 25 of 60). Gallstones developed within 1.8 +/- 1.1 years
      in 17% of patients (n = 8 of 48) with a normal pretransplantation ultrasonogram.
      Biliary colic or gallstone pancreatitis developed 2 +/- 1.2 years after
      transplantation in 58% of patients (n = 7 of 12) with asymptomatic gallstones
      diagnosed before transplantation. The overall incidence of cholecystectomy or
      cholecystectomy with Roux-en-Y cystojejunostomy was 40% (n = 24). Both open
      cholecystectomy (n = 5) and laparoscopic cholecystectomy (n = 19) were performed
      without significant complications. Recovery is significantly more rapid (p <
      0.05) after laparoscopic cholecystectomy versus open cholecystectomy (1 week
      versus 3 weeks). CONCLUSIONS: This analysis indicates that transplant candidates
      who have gallstones on pretransplantation evaluation or in whom gallstones
      develop after transplantation should undergo laparoscopic cholecystectomy at the
      earliest time in their posttransplantation course (i.e., 3 months) regardless of
      their symptomatic status. Removal of the diseased gallbladder not only simplifies
      the evaluation of cholestatic jaundice by eliminating the need for multiple
      ultrasonograms to exclude acute cholecystitis or choledocholithiasis but also
      safely minimizes the risk of the development of severe biliary complications.

PMID- 7578169
TI  - Epstein-Barr virus infection in heart and heart-lung transplant recipients:
      incidence and clinical impact.
AB  - BACKGROUND: A retrospective serologic study was made of 67 heart-lung and 295
      heart transplant recipients (with transplantations at Papworth Hospital,
      Cambridge, England) to determine the incidence and clinical impact of Epstein
      Barr virus infection. METHODS: Epstein-Barr virus capsid antigen
      immunofluorescence tests were performed, and the antibody avidity was determined
      by modifying the washing procedure to include a mild reducing agent (8M urea).
      RESULTS: This testing showed that 6.0% of the patients had primary Epstein-Barr
      virus infections, whereas 17.4% had the reactivation of a past infection. Primary
      infections were only detected in patients who were Epstein-Barr virus antibody
      negative before transplantation, who had received an organ from an Epstein-Barr
      virus antibody-positive donor. Of the patients with serologically proven Epstein
      Barr virus infections, 52.9% had symptoms. Although these were generally mild,
      five heart and two heart-lung transplant recipients had malignant lymphoma and
      one heart and one heart-lung transplant recipient had lymphoproliferative disease
      after Epstein-Barr virus infection. Additional four heart transplant recipients
      had lymphoma after transplantation. None of these four patients had evidence of
      active Epstein-Barr virus infection; one was Epstein-Barr virus antibody-negative
      during the study period and three had stable Epstein-Barr virus virus capsid
      antigen immunoglobulin G titers throughout. CONCLUSIONS: Epstein-Barr virus
      infection in organ transplant recipients may lead on to life-threatening
      lymphoproliferative disease or lymphoma. For this reason it may be beneficial to
      monitor patients after transplantation for evidence of Epstein-Barr virus
      infection and to follow the progress of those affected.

PMID- 7578170
TI  - Impaired left atrial function after heart transplantation: disparate contribution
      of donor and recipient atrial components studied on-line with quantitative
      echocardiography.
AB  - BACKGROUND: Because of a lack of noninvasive techniques, left atrial function
      after orthotopic heart transplantation has not been well characterized. METHODS:
      Global left atrial performance and the relative contributions of donor and
      recipient atrial components were assessed with transthoracic echocardiography
      with on-line automated border detection in 20 patients with normal left
      ventricular systolic function 1 to 6 years (mean 3.5 +/- 0.3 years [standard
      error]) after heart transplantation. RESULTS: The mean left atrial area at
      ventricular end-systole was 22.9 +/- 1.5 cm2, the mean left atrial emptying
      fraction ([left atrial area at ventricular end-systole--left atrial area at
      ventricular end-diastole]/left atrial area at ventricular end-systole) was 29.7%
      +/- 2.6%, and the fractional area change caused by active contraction was 27.8%
      +/- 3.1%. Compared with controls, patients had larger atria, depressed emptying,
      and reduced fractional active contraction. Although the recipient to donor area
      ratio was 3:2, the proportion of atrial emptying (change in area from mid-to-late
      ventricular diastole divided by the total left atrial change during ventricular
      diastole) contributed by the recipient component was greatly diminished when
      compared with that of the donor component (1.4% +/- 3.5% versus 31% +/- 2.7%) (p
      = 0.0001). CONCLUSIONS: Despite being anatomically smaller, the functional
      contractile contribution of the donor component dominated atrial emptying. Thus,
      after heart transplantation, global left atrial function is depressed,
      predominantly because of dysfunction of the recipient atrial component.

PMID- 7578171
TI  - Changing patterns in donor and recipient risk: a 10-year evolution in one heart
      transplant center.
AB  - BACKGROUND: Expansion of the donor pool and liberalization of recipient criteria
      have occurred since the introduction of cyclosporine for heart transplantation.
      METHODS: We sought to evaluate the impact of these changes on outcome during a 10
      year period in one program. A total of 251 transplantations were retrospectively
      reviewed and divided into two periods (1984 to 1989 and 1990 to 1994). RESULTS:
      In the latter period, there were increases in donor and recipient age, degree of
      weight mismatch, ischemic time, bypass time, and severity of illness in the
      recipient before transplantation as judged by status at the time of
      transplantation and preoperative requirements for pharmacologic or mechanical
      support. Despite these changes, time to hospital discharge decreased and a trend
      to improved survival was seen with the use of Kaplan-Meier analysis. CONCLUSIONS:
      These findings suggest that improvements in perioperative and posttransplantation
      care have permitted a safe expansion of both the donor pool and recipient
      criteria for transplantation.

PMID- 7578173
TI  - Creatine kinase MB isoforms: a potential predictor of acute cardiac allograft
      rejection.
AB  - BACKGROUND: Noninvasive studies to detect or predict acute allograft rejection
      after heart transplantation have failed to be sufficiently reliable to substitute
      for endomyocardial biopsy. Isoforms of creatine kinase MB isoenzyme (MB2 and MB1)
      are extremely sensitive markers of ischemic myocardial damage and, in theory, may
      be elevated in cardiac allograft rejection when myocardial necrosis is visible on
      microscopy (International Society for Heart and Lung Transplantation grade 2 or
      greater). METHODS: We examined, prospectively, the endomyocardial biopsy
      specimens (n = 256) of 50 consecutive patients undergoing orthotopic heart
      transplantation. Blood samples for creatine kinase MB isoforms (n = 527) were
      taken immediately before endomyocardial biopsy and at intervals between biopsies.
      RESULTS: The median ratio of MB2/MB1 in plasma samples taken at the time of
      biopsy for grades 2 and 3 was not significantly different from the ratio from
      biopsy specimens graded 0 and 1 (1.65 versus 1.33; p = Not significant). The
      sensitivity for diagnosing a moderately severe rejection was 47% with a
      specificity of 58%. However, in patients with significant acute rejection (grades
      2 and 3) in whom consecutive samples were collected, the MB2/MB1 ratio was
      significantly increased before histologic changes seen on biopsy in 13 of 16
      rejection episodes by a mean of 14 days. The sensitivity for predicting rejection
      (grade 2 or 3) before endomyocardial biopsy was 60% with a specificity of 71%
      (positive predictive value 43%, negative predictive value 86%). CONCLUSIONS:
      Creatine kinase MB isoforms may predict the occurrence of acute rejection before
      histologic evidence seen on endomyocardial biopsy.

PMID- 7578172
TI  - Combined antiviral and immunoglobulin therapy as prophylaxis against
      cytomegalovirus infection after heart transplantation.
AB  - BACKGROUND: Cytomegalovirus is a frequent cause of infection and morbidity after
      heart transplantation, especially in patients treated with antilymphocytic drugs
      where the incidence may be as high as 50%. METHODS: To determine the efficacy of
      combined antiviral and intravenous immune globulin therapy for prevention of
      cytomegalovirus disease in transplant recipients receiving OKT3 and to compare
      two different antiviral drug regimens, we reviewed 115 transplant recipients from
      December 1988 to December 1993 who survived for more than 30 days. Of these, 29
      received oral acyclovir for 3 months (group A) and 86 received intravenous
      ganciclovir for 2 weeks followed by oral acyclovir up to 3 months (group G); all
      received six infusions of 5% intravenous immune globulin over 2 months. All
      patients had OKT3 for 10 to 14 days and triple-drug immunosuppression. RESULTS:
      Cytomegalovirus disease (pneumonitis, gastroenteritis, or leukopenia with fever)
      occurred in 10% of patients (12 of 115 patients) and was confirmed by positive
      culture, typical microscopic inclusions, or polymerase chain reaction. In 91
      seropositive recipients, there was a trend to less cytomegalovirus disease in
      group G (3.0%, 2 of 67 patients) than in group A (12.5%, 3 of 24 patients) (p =
      0.11), which was more apparent in recipients with seropositive donors where the
      incidence was reduced from 16.7% (group A) to 2.4% (group G; p = 0.08). In 24
      seronegative recipients, cytomegalovirus disease incidence was higher overall and
      not significantly less in group G (26%, 5 of 19 patients) than in group A (40%,
      two of five patients) (p = Not significant). CONCLUSIONS: Prophylaxis with
      combined antiviral and immune globulin therapy produces a low (10%) incidence of
      cytomegalovirus disease in OKT3-treated heart transplant recipients. In
      seropositive recipients treated with combined therapy, ganciclovir may be more
      effective than acyclovir. Larger trials and more aggressive prophylactic
      strategies are needed in seronegative patients who receive hearts from
      seropositive donors.

PMID- 7578174
TI  - Optimal size matching in single lung transplantation.
AB  - BACKGROUND: Single lung transplantation for patients with end-stage obstructive
      lung disease has been highly effective in providing symptomatic relief, and it
      has been performed at a much increased frequency since 1983. However, there still
      lacks a convincing study showing the effect of size match and other preoperative
      variables in predicting functional outcome of patients after transplantation.
      METHODS: We evaluated 23 single lung transplantations performed for obstructive
      lung disease over a 34-month period. Multiple physiologic variables and size
      match criteria were evaluated for their contribution in determining the
      postoperative forced expiratory volume in 1 second at 3 months after
      transplantation. RESULTS: The size match ratio that was based on inframammary
      chest wall circumference was the most useful criterion to adopt, and the optimal
      donor/recipient size match ratio was 0.89. Furthermore, forced expiratory volume
      in 1 second at 3 months after transplantation could be predicted with a simple
      mathematical model that was based on the size match ratio and the recipient's
      calculated vital capacity of the transplanted hemithorax. CONCLUSIONS: This model
      could be applied in a clinical setting to maximize functional outcome of the
      recipients undergoing single lung transplantation.

PMID- 7578175
TI  - Amelioration of reperfusion injury by pentoxifylline after lung transplantation.
      The Universite Paris-Sud Lung Transplant Group.
AB  - BACKGROUND: Pentoxifylline attenuates neutrophil-mediated lung injury in several
      models of acute lung inflammation. METHODS: Because pulmonary neutrophil
      sequestration is the main determinant of lung reperfusion injury, we sought to
      determine whether pentoxifylline prevented reperfusion injury in isolated
      perfused rat lung (4-hour cold ischemia, 1-hour reperfusion; pentoxifylline
      intravenously 40 mg) and in pigs after left lung allotransplantation (24-hour
      cold ischemia, 4-hour reperfusion; pentoxifylline 1.5 mg/kg/hr intravenously). In
      the pigs, inflatable cuffs placed around each pulmonary artery enabled us to
      evaluate each lung separately. RESULTS: In rat lungs, the coefficient of lung
      permeability increased by 75% +/- 10% in controls and by 3% +/- 2% (p < 0.01) in
      pentoxifylline-treated lungs. In the pigs, with blood flow to the transplanted
      lung alone and ventilation with an inspired oxygen fraction of 1, the arterial
      oxygen tension was greater in the pentoxifylline group than in the control group
      (423 +/- 49 versus 265 +/- 43 mm Hg, p < 0.05), whereas the total pulmonary
      vascular resistance was lower (15 +/- 1 versus 30 +/- 9 mm Hg/L/min, p < 0.02).
      After reperfusion, the decrease in circulating leukocyte count fell by 35% +/- 3%
      in the control group and remained unchanged in the pentoxifylline group, and the
      leukocytes count per microscopic field in the transplanted lung was lower in the
      pentoxifylline group than in the control group (15 +/- 2 versus 140 +/- 50, p <
      0.02). CONCLUSIONS: These data suggest that pentoxifylline prevented reperfusion
      injury by decreasing neutrophil lung sequestration.

PMID- 7578176
TI  - Incidence of phrenic neuropathy after isolated lung transplantation. The Loyola
      University Lung Transplant Group.
AB  - BACKGROUND: Isolated lung transplantation is a viable therapeutic option for many
      patients with end-stage pulmonary disease. Other intrathoracic surgical
      procedures have a well documented incidence of phrenic nerve dysfunction,
      although the incidence after lung transplantation has not been studied. METHODS:
      Thirty-one patients who underwent lung transplantation were evaluated for
      evidence of phrenic nerve dysfunction and subsequent recovery. Risk factors
      contributing to the incidence of injury were examined. Phrenic nerve injury was
      defined by two separate diagnostic tests (Transcutaneous Phrenic Nerve Conduction
      Studies and Fluoroscopic evaluation of diaphragmatic movement) used in
      combination. RESULTS: Of the 27 patients who were completely evaluated after the
      operation, eight had defining criteria for nerve injury--an incidence of 29.6%.
      Of those affected, the majority of injuries (89%) resulted in complete paralysis
      of the affected hemidiaphragm. The highest incidence of injury occurred in
      patients who underwent bilateral single lung transplantation (41%), with the
      right phrenic nerve being injured most often (78%). Fortunately, no significant
      postoperative morbidity was attributable to the occurrence of phrenic nerve
      injury when compared with those patients who did not sustain injury. CONCLUSIONS:
      The analysis of possible risk factors resulted in the hypothesis that the likely
      mechanism of injury in these patients was due to stretching or direct
      instrumentation of the nerve, and thus measures should be instituted to minimize
      the possibility of injury.

PMID- 7578177
TI  - Comparison of outcomes after single and bilateral lung transplantation for
      obstructive lung disease.
AB  - BACKGROUND AND METHODS: To determine the long-term functional outcome for single
      versus bilateral lung transplant for nonseptic obstructive lung disease, we
      compared the results from 39 single and nine bilateral lung transplant
      procedures. The nine bilateral lung transplants included three en bloc double
      lung and six bilateral sequential lung transplants. RESULTS: Early deaths within
      30 days of transplantation occurred in two of nine (22%) bilateral and 4 of 39
      (10%) single lung transplants (p = Not significant). Compared with pretransplant
      values, pulmonary function as assessed by the spirometric indexes of the percent
      predicted forced vital capacity, forced expiratory volume in one second, forced
      expiratory volume in one second/forced vital capacity, and forced expiratory flow
      at 25% and 75% of forced vital capacity improved significantly up to at least 12
      months after transplantation for both single and bilateral lung transplant
      recipients. The degree of pulmonary function improvement was better in single as
      compared with bilateral lung recipients. By 6 months after transplantation, all
      but one single and all bilateral lung recipients were in New York Heart
      Association class I or II (p = Not significant). One-year survival was
      significantly better after single (77%) compared with after bilateral lung
      transplantation (35%) (p < 0.05). CONCLUSIONS: These results suggest that single
      lung transplantation is the procedure of choice for patients with nonseptic
      obstructive lung disease.

PMID- 7578179
TI  - Proposal of a working left heart model with a heterotopic transplantation
      technique in rats.
AB  - BACKGROUND: A heterotopically transplanted rat heart model described by Ono and
      Lindsey in 1969 has been widely used as a fundamental animal model of heart
      transplantation. However this "nonworking" model is greatly different from the
      orthotopic heart in view of left ventricular work, in which the experimental
      results obtained may not always reflect the clinical setting with an orthotopic
      transplanted "working" heart. We herein propose a new "working" left heart model
      in rats using a heterotopic abdominal transplantation technique by modifying the
      method of Ono and Lindsey. METHODS: First, a donor heart graft and a recipient
      were prepared in the conventional fashion. Second, the donor heart was tailored
      by the ligation of main pulmonary artery and the removal of tricuspid valve and
      interatrial septum. Third, the ascending aorta and right atrium of the donor
      heart were anastomosed to the infrarenal abdominal aorta and to the inferior vena
      cava of the recipient, respectively. Consequently, the left atrium and ventricle
      of heart graft were loaded with the blood from the right atrium through the
      interatrial communication. RESULTS: This surgical procedure required an average
      of 58 minutes and had negligible operative risk. The donor left ventricle
      produced a systolic blood pressure almost equal to the recipient's aortic
      pressure and maintained vigorous beat. CONCLUSIONS: This model is easily
      reproducible and would be useful for various studies on heart transplantation.

PMID- 7578178
TI  - Beneficial effect of initial warm crystalloid reperfusion in 6-hour lung
      preservation.
AB  - BACKGROUND: To achieve successful lung transplantation, it is essential to
      minimize reperfusion injury occurring as a result of metabolite accumulation
      during the preservation period or at the time of initial interaction of blood
      with constricted pulmonary vasculature. Initial reperfusion with warm crystalloid
      solution may be advantageous in preventing this injury. METHODS: This study was
      designed to evaluate the effect of low-potassium (4 mmol/L) dextran (1%) solution
      as the initial warming solution after 6 hours of hypothermic storage. In 23 New
      Zealand White rabbits the lungs were flushed with low-potassium dextran solution
      (10 degrees C, 40 ml/kg, 600 cm H2O), excised, inflated with room air, and stored
      in a low-potassium dextran solution (10 degrees C) for 6 hours. After storage,
      the lungs were divided into two groups. Group 1 (n = 8) was reperfused with warm
      low potassium dextran for 4 minutes, at 37 degrees C followed by blood
      reperfusion for 30 minutes at 37 degrees C. Group II (n = 15) was reperfused only
      with blood for 30 minutes at 37 C. The mean pulmonary vascular resistance
      measured during cold flush and prior to storage was similar in both groups (group
      I = 20.0 +/- 5.9 mm Hg.sec/ml, group II = 19.3 +/- 1.9 mm Hg.sec/ml). RESULTS:
      During reperfusion, only 4 of the 15 lungs in group II maintained an acceptable
      (< 80 mm Hg) mean pulmonary artery pressure; six failed immediately. All eight
      lungs in group I completed the 30-minute reperfusion (p < 0.005). The mean
      pulmonary artery pressure was significantly less, and effluent oxygen tension was
      significantly greater in group I during reperfusion. CONCLUSIONS: In this
      experimental model, initial warm reperfusion with low-potassium dextran
      ameliorated the deleterious effects of reperfusion, thus providing an environment
      to improve lung preservation.

PMID- 7578180
TI  - Orthotopic transplantation for total anomalous pulmonary venous connection
      associated with complex congenital heart disease.
AB  - BACKGROUND: When total anomalous pulmonary venous connection is associated with
      other complex cardiac malformations, early and late postsurgical morbidity and
      mortality are excessive. METHODS: In an attempt to modify this outcome, twelve
      children (4 days to 6.8 years of age) with total anomalous pulmonary venous
      connection and various congenital cardiac defects were treated with orthotopic
      heart transplantation. Associated cardiac diagnoses included the following:
      hypoplastic left heart syndrome (n = 2), unbalanced atrioventricular canal with
      pulmonary atresia (n = 2), and single ventricle with severe pulmonary stenosis (n
      = 3) or atresia (n = 5). Two patients had situs inversus, and two had
      dextrocardia with situs ambiguous. Eight patients had asplenia and one had
      polysplenia. Palliative pretransplantation procedures in five patients included
      the following: systemic to pulmonary artery shunt (n = 5), atrioventricular valve
      annuloplasty (n = 1) and classical Glenn shunt (n = 1). The donor left atrium was
      anastomosed directly to a common pulmonary venous pool in nine patients; whereas
      three children required complex reconstruction to baffle the pulmonary venous
      flow to the donor left atrium. RESULTS: There was one operative death related to
      an oversized heart and vena caval thrombosis. Follow-up ranged from 16 months to
      4.5 years (average 3 years). In two patients (18%) pulmonary venous obstruction
      developed 3 and 4 months after transplantation. Reoperation to relieve the
      obstruction was successful in one patient. The second patient underwent three
      such reoperations and died of sepsis 10 months after orthotopic heart
      transplantation. CONCLUSION: Orthotopic transplantation is a viable option for
      children with complex total anomalous pulmonary venous connection that precludes
      a biventricular repair. Transplantation may improve the dismal prognosis of those
      children, but it does not eliminate the potential for late pulmonary venous
      obstruction.

PMID- 7578181
TI  - Congenital heart disease with ductal-dependent systemic perfusion: Doppler
      ultrasonography flow velocities are altered by changes in the fraction of
      inspired oxygen.
AB  - BACKGROUND: An unfavorable balance in systemic and pulmonary perfusion may occur
      in neonates with ductal-dependent systemic perfusion while being treated with
      prostaglandin E1 before surgical palliation or transplantation. At our
      institution, we adjust the fraction of inspired oxygen, with supplemental
      nitrogen if needed, to control pulmonary vascular tone and maintain systemic
      oxygen saturations near 75%. METHODS: We performed a noninvasive Doppler
      ultrasound study in 10 patients to determine whether velocity time integrals in
      the descending aorta and middle cerebral arteries and the peak velocity at the
      foramen ovale were acutely altered by changes in the fraction of inspired oxygen.
      Measurements were performed after 10- to 15-minute intervals of breathing 14% to
      19%, 21%, and 35% oxygen. RESULTS: Antegrade descending aortic velocity time
      integrals did not change significantly when these patients breathed different
      amounts of oxygen; however, the retrograde velocity time integral in the
      descending aorta and the peak velocity of left-to-right shunt at the foramen
      ovale increased with increasing amounts of inspired oxygen. The ratio of
      antegrade to retrograde velocity time integrals in the descending aorta was
      greater with supplemental nitrogen than with supplemental oxygen. Middle cerebral
      arterial velocity time integrals were not significantly greater with supplemental
      nitrogen than with supplemental oxygen (p = 0.061). CONCLUSIONS: Systemic and
      interatrial Doppler velocities are acutely influenced by the fraction of inspired
      oxygen in neonates with ductal-dependent systemic perfusion.

PMID- 7578182
TI  - Methotrexate therapy for complex graft rejection in pediatric heart transplant
      recipients. The Pediatric Heart Transplant Team--Loma Linda.
AB  - BACKGROUND: We retrospectively reviewed all pediatric heart transplant recipients
      at Loma Linda University Medical Center between January 1990 and September 1993
      to evaluate the efficacy and safety of methotrexate when it is used for the
      treatment of graft rejection. METHODS: Twenty-eight of 156 patients (18%)
      received methotrexate therapy. The dose used for recurrent rejection was 10
      mg/m2/week given every 12 hours for three doses. Rejection history, complete
      blood counts, liver function tests, and infectious complications were reviewed.
      RESULTS: Eighteen patients were treated for recurrent rejection. Methotrexate was
      begun at a median of 115 days (13 to 1093 days). Older patients were more likely
      to receive methotrexate (p < 0.01). Efficacy was assessed as rejection episodes
      (mean +/- standard deviation) occurring in the 2 months before methotrexate
      administration compared with the 2 months after methotrexate administration and
      fell from 2.0 +/- 0.2 to 0.6 +/- 0.2 episodes (p < 0.001). The rejection rate
      (rejections per patient-month) fell in treated patients to a rate similar to
      patients who did not receive methotrexate. Two patients (11%) died while
      receiving methotrexate. An additional nine patients were treated for acute
      rejection with hemodynamic compromise, and one was treated for graft-versus-host
      disease. The incidence of significant infections was 50% (but no deaths were due
      to infection) during methotrexate therapy in all patients treated (n = 28). The
      minimum white blood cell count in the first month of methotrexate therapy
      occurred at 2 weeks (median of 2700 to 3500 x 10(6) cells/L). Only one patient
      had elevated transaminase levels. CONCLUSION: Methotrexate is an effective and
      safe adjunct in the management of chronic pediatric cardiac graft rejection.

PMID- 7578183
TI  - Transforming the "unacceptable" donor: outcomes from the adoption of a
      standardized donor management technique.
AB  - BACKGROUND: Donor management remains one of the most neglected areas of
      transplantation. A comprehensive donor management regimen has been developed. The
      results of the application of this strategy form the basis of this report.
      METHODS: Full hemodynamic data were collected from 150 multiorgan donors between
      October 1990 and August 1993. The data were collected at the time of donor team
      arrival, after insertion of a pulmonary artery floatation catheter and
      immediately before cardiac excision. RESULTS: Fifty-two donors (35%) fell well
      outside our minimum acceptance criteria on arrival. Twenty-one of fifty-two had a
      mean arterial pressure less than 55 mm Hg (mean 47 mm Hg) despite inotropic
      support in most cases; 10 of 52 had a central venous pressure greater than 15 mm
      Hg (mean 18.0 mm Hg); 2 of 52 had a high inotrope requirement greater than 20
      micrograms/kg/min (mean 25 micrograms/kg/min). After the insertion of a pulmonary
      artery floatation catheter, an additional 13 of 52 donors were found to have a
      pulmonary capillary wedge pressure greater than 15 mm Hg (mean 19.8 mm Hg), and
      the final 6 of 52 had a low left ventricular stroke work index, less than 15 gm
      (mean 12.8 gm). After optimal management, including hormone replacement 44 of 52
      donors yielded transplantable organs (29 hearts, 15 heart and lung blocks).
      Thirty-seven of forty-four patients (84%) were alive and well from 13 to 48
      months after transplantation. There were five early deaths (11%) caused by
      infection (heart), adult respiratory distress syndrome (heart), arrhythmia
      (heart), cerebrovascular event (heart and lung), and infection (heart, lung, and
      liver). Two late deaths (5%) occurred as a result of tamponade (3 months, heart)
      and infection (14 months, heart and lung). Eight of fifty-two organs were still
      unsuitable for transplantation after optimum management during the splanchnic
      dissection as a result of inotrope dependency (n = 4), left ventricular
      hypertrophy (n = 2), and coronary artery disease (n = 2). CONCLUSIONS: The data
      indicate that, of the organs which initially fall outside our transplant
      acceptance criteria, 92% are capable of functional resuscitation. Conversely,
      superficial assessment may not show compromised function. Optimizing
      cardiovascular performance also has important implications for the viability of
      all transplantable organs. This aggressive approach to donor management has
      resulted in the transplantation of 44 donor hearts that may otherwise have been
      turned down or inappropriately managed.

PMID- 7578185
TI  - Natural antipig xenoantibody is absent in neonatal human serum.
AB  - BACKGROUND: Discordant xenotransplantation represents an attractive alternative
      to allotransplantation in light of the current shortage of donor organs suitable
      for heart allotransplantation. Unfortunately, discordant xenotransplantation is
      still limited by hyperacute rejection, a process thought to be mediated by
      natural antixenodonor antibodies. On the basis of our previous findings that
      cytotoxic natural xenoantibodies are immunoglobulin M in nature and that natural
      immunoglobulin M xenoantibodies are barely detectable in neonatal baboon serum,
      we postulated that immunoglobulin M xenoantibodies may be absent from newborn
      human serum. METHODS: Neonatal human sera were obtained from the cord blood of
      normal term infants and pooled. Pooled adult human sera were used as a control. A
      whole cell enzyme-linked immunosorbent assay and a complement-mediated
      cytotoxicity assay were performed to determine the binding and cytotoxicity of
      these xenoantibodies to pig aortic endothelial cells and pig lymphocytes.
      RESULTS: Neonatal human sera did not show binding of immunoglobulin M
      xenoantibodies to pig aortic endothelial cells or lymphocytes. However, low level
      binding of immunoglobulin G xenoantibodies was detected to pig endothelial cells
      and lymphocytes. In contrast, adult human sera showed significant binding of both
      natural immunoglobulin M and G xenoantibodies to pig aortic endothelial cells and
      lymphocytes. In addition, adult human immunoglobulin M xenoantibodies bound with
      similar avidity to both cultured adult and neonatal pig aortic endothelial cells.
      Although neonatal human sera were not cytotoxic to target cells, adult sera were
      cytotoxic to both pig aortic endothelial cells and pig lymphocytes. Our findings
      indicate that neonatal human sera lack natural antipig immunoglobulin M
      xenoantibodies, and therefore, neonatal human serum is not cytotoxic to pig
      endothelial cells or lymphocytes. Like adult pig endothelial cells, neonatal pig
      endothelial cells may also express similar membrane xenoantigens recognized by
      natural immunoglobulin M xenoantibodies. CONCLUSIONS: The absence of cytotoxic
      natural immunoglobulin M xenoantibodies in the neonate suggests that discordant
      xenotransplantation may be feasible in the neonate.

PMID- 7578184
TI  - Increased incidence of chronotropic incompetence in older donor hearts.
AB  - BACKGROUND: Previous Registry studies have reported that heart transplantation
      with older donor hearts is associated with a more than twofold increase in early
      mortality. METHODS: An analysis of 77 consecutive patients undergoing heart
      transplantations at our institution between June 1988 and July 1994 was performed
      to assess the effect of donor age on mortality and morbidity. Recipients were
      grouped into those receiving hearts from younger donors (aged < 40 years, n = 60)
      and those receiving hearts from older donors (aged > 40 years, n = 17). RESULTS:
      There were two deaths within the first 30 days in the younger donor group and no
      deaths in the other group. One-year survival rate was 95% and 100% for the
      "younger" and "older" groups, respectively. The mean recipient age of the younger
      donor group was lower (46 +/- 14 years) compared with the older donor group (57
      +/- 7 years). Morbidity was compared between the two groups; the length of
      hospital stay (22.6 +/- 15.8 days versus 21.3 +/- 9.4 days), the graft ejection
      fraction at 1 week (64% +/- 5% versus 62% +/- 7%), and the mean number of
      rejection episodes within the first 3 months (0.79 versus 0.65) were not
      statistically different between the two groups. However, the incidence of
      chronotropic incompetence requiring permanent pacemaker implantation was
      significantly greater in the group who received older donor hearts (41.2% versus
      10.3%, p < 0.05), independent of the ischemic time. CONCLUSIONS: This study shows
      that older donor hearts may be used safely in selected patients with excellent
      outcome, although there is an increased incidence of chronotropic incompetence
      requiring implantation of permanent pacemakers.

PMID- 7578186
TI  - Eosinophilic explant carditis with eosinophilia: ?Hypersensitivity to dobutamine
      infusion.
AB  - BACKGROUND: Eosinophilic carditis with peripheral eosinophilia has been observed
      in a number of clinical situations. This report describes this association in
      patients undergoing heart transplantation and offers a possible explanation.
      METHODS: The clinical records and explanted hearts of 31 consecutive patients who
      received primary orthotopic heart transplants were reviewed. Clinical features
      particularly analyzed included the following: age, cardiac status and assistance
      devices, catheterizations, medical or surgical disorders including parasites,
      tryptophane exposure, medications, and peripheral blood counts. Pathologic
      features particularly studied included the following: dilatation and hypertrophy,
      fibrosis, mural thrombi, carditis, eosinophils, myocardial necrosis, vasculitis,
      valvular disease, and coronary artery disease. Prior endomyocardial biopsy
      specimens were also reviewed. RESULTS: Seven patients had eosinophilic carditis
      compatible with hypersensitivity carditis. Eight had eosinophilia. All patients
      with carditis received intravenous dobutamine (Dobutrex solution) continuously
      for more than 1 month immediately preceding transplantation. All patients with
      eosinophilia received intravenous dobutamine continuously for 15 days or longer
      and exhibited eosinophilia only during dobutamine therapy with the exception of
      one patient in whom eosinophilia was observed 8 days after cessation of 8 days of
      therapy. Among 13 patients who received dobutamine for more than a month
      immediately before transplantation, nine had eosinophilic carditis, peripheral
      eosinophilia, or both. CONCLUSIONS: Prolonged continuous intravenous
      administration of dobutamine was associated with eosinophilic carditis and
      eosinophilia. No other clinical factor with a relationship to either eosinophilia
      or carditis was identified. The responsible agent may have been a preservative in
      the dobutamine solution, sodium bisulfite.

PMID- 7578187
TI  - Transbronchial biopsy in heart and lung transplantation: clinicopathologic
      correlations.
AB  - BACKGROUND AND METHODS: We reviewed and correlated the histologic and clinical
      records for the 1027 transbronchial biopsies performed, as clinically indicated,
      in 313 heart and lung transplant recipients in the Harefield Transplant Unit from
      1988 through 1991. Three pieces of lower lobe or radiologically abnormal lung
      were routinely sent for histologic diagnosis. Clinical diagnoses of rejection and
      infection were based on symptomatologic, radiologic, and bacteriologic findings
      and response to appropriate therapy. Standard histopathologic technology and
      diagnostic criteria were used, including the Working Formulation for the
      standardization of nomenclature in the diagnosis of heart and lung rejection
      grading. RESULTS: Rejection was the most common finding (22.2%) and showed good
      clinicopathologic correlation. With unequivocal histologic features of rejection
      (Working Formulation grade A1 or above), specificity (clinical agreement with
      biopsy diagnosis) was 93.1% and sensitivity (clinical rejection confirmed by
      transbronchial biopsy) was 61%. Sensitivity increased to 77% if unsatisfactory
      specimens were excluded. Possible/probable rejection only was reported in 83
      specimens; there were technically unsatisfactory, showed only minimal
      perivascular infiltrates, or had infiltrates limited to one vessel; 71% of these
      did have clinical rejection. Infection, excluding opportunistic, was reported in
      18.5% of biopsy specimens; specificity was 70.5% and sensitivity 51.3% (both
      rising by 9%), with unsatisfactory specimens excluded. Histologic features of
      both rejection and infection were seen in 47 transbronchial biopsy specimens
      (4.7%). Where both components appeared definite specificity was 66.7%, but where
      either had been doubtful the clinical diagnosis was most often rejection.
      Sensitivity was also 66.7%. Cytomegalovirus inclusions were identified in 12.1%
      of biopsy specimens, with specificity of 91% and sensitivity of 83.5%.
      Sensitivity (88%) and specificity (100%) were both high for the 17 cases with
      pneumocystis infections. Sensitivity for the 25 transbronchial biopsy specimens
      from fungal infections was only 20%. Sensitivity was also poor (27.7%) in
      obliterative bronchiolitis, although specificity was 75%. Almost a third of
      transbronchial biopsy specimens from patients with obliterative bronchiolitis
      were unsatisfactory. Pneumonitis was the only change noted in 68 biopsy
      specimens. Most correlated with clinical status, but 26.5% were from patients
      with active rejection. Nonspecific changes or no significant pathologic condition
      was seen in 278 transbronchial biopsy specimens; over a third of these were from
      patients with clinical rejection (17.7%) or infection (18%) and 6.5% were from
      obliterative bronchiolitis cases. Excluding 78 technically unsatisfactory
      specimens reduced the proportion of false negative findings in rejection and
      infection by 6% and 4%, respectively. CONCLUSIONS: We found that transbronchial
      biopsies consisting of three adequate pieces of lung parenchyma correlated well
      with clinical rejections and infections other than fungal but was of limited
      value in confirming a diagnosis of obliterative bronchiolitis or fungal
      infection.

PMID- 7578188
TI  - Persistence of interstitial inflammation after episodes of cardiac rejection
      associated with systemic infection.
AB  - BACKGROUND: To determine whether systemic infection has an effect on cardiac
      allografts, we compared heart transplant biopsy specimens showing acute cardiac
      rejection in patients with and without associated systemic infection. METHODS:
      Systemic infection was defined as positive bacterial, viral, or fungal cultures
      with systemic symptoms such as sepsis, fever, or malaise. Patients were
      identified by chart review to verify the presence or absence of infection and the
      cardiac biopsy specimens were examined for evidence of rejection. Eight patients
      (eight episodes of treated acute rejection) with evidence of systemic infection
      and 11 patients (14 episodes of treated acute rejection) without evidence of
      systemic infection were identified. RESULTS: Patients with rejection and
      infection showed persistent interstitial inflammation longer than patients with
      only rejection and was most often represented by International Society for Heart
      and Lung Transplantation rejection grade 1B. Days to resolution or last biopsy
      was 20 to 602 days (mean 196 days) for patients with rejection and infection
      versus 15 to 133 days (mean 60 days) for patients with rejection alone. Results
      of two-tailed, unpaired t-test comparing the number of days of persistent
      inflammatory infiltrates in the patients with and without infection were
      statistically significant (p = 0.0192). CONCLUSIONS: Heart transplant recipients
      with treated acute rejection and systemic infection more frequently have
      persistent interstitial inflammatory infiltrates than do heart cardiac transplant
      recipients with treated acute rejection and no associated infection. No impact of
      acute rejection or associated infection on the incidence of allograft coronary
      artery disease was apparent. Although further evaluation of these findings is
      necessary, we speculate that heart transplant recipients with systemic infection
      and acute rejection have greater immunologic activity leading to persistent
      interstitial inflammation and may possibly be associated with a higher incidence
      of chronic rejection.

PMID- 7578189
TI  - Liposomal amphotericin B in three lung transplant recipients. The Groningen Lung
      Transplantation Group.
AB  - BACKGROUND: Opportunistic fungal infections are an important cause of morbidity
      and mortality in solid organ transplant recipients. Conventional therapy with
      amphotericin B is often restricted by toxicity. However, side effects and
      toxicity of liposomal amphotericin B are reported to be limited. METHODS: Three
      lung transplant recipients with proven infections with Aspergillus fumigatus were
      treated with liposomal amphotericin B. RESULTS: Therapy with liposomal
      amphotericin B in our patients showed more side effects and (nephro)toxicity than
      suggested by previous reports. However, it did not result in cessation of
      treatment prematurely, and patients were able to complete the antifungal therapy
      with good clinical success. CONCLUSIONS: Treatment with liposomal amphotericin B
      represents an advance from conventional amphotericin B therapy.

PMID- 7578190
TI  - Refractory immune thrombocytopenia after heart transplantation: a case report.
AB  - Chronic immune thrombocytopenia responds to steroids and splenectomy in
      approximately 80% of the patients. Intravenous immunoglobulin, plasmapheresis,
      combination chemotherapy, and androgens may help in refractory cases. This report
      describes the course and management of refractory immune thrombocytopenia after
      heart transplantation.

PMID- 7578192
TI  - Transesophageal echocardiographic identification of a malpositioned
      extracorporeal membrane oxygenation cannula.
AB  - Transesophageal echocardiography identified malposition of an extracorporeal
      membrane oxygenation venous cannula across the interatrial septum into the left
      atrium and the presence of a clot within the cannula's lumen. Transesophageal
      echocardiography also guided the withdrawal of the cannula into the inferior vena
      cava.

PMID- 7578191
TI  - Prosthetic abdominal fascial closure after ventricular assist device insertion.
AB  - The requirement for adequate abdominal domain does not allow placement of left
      ventricular assist devices into patients with body surface areas less than 1.5
      m2. We describe a technique for prosthetic abdominal wall closure that may allow
      placement of devices into smaller recipients, primarily children and women.

PMID- 7578193
TI  - Extracorporeal photochemotherapy treatment for acute lung rejection episode.
AB  - BACKGROUND AND METHODS: We investigated extracorporeal photochemotherapy--which
      consists of the collection of blood mononuclear cells by means of a cell
      separator, their exposure to ultraviolet A light in the presence of a
      photoactivatable molecule such as 8-methoxypsoralen, and their intravenous
      reinjection into the patient--for the treatment of an acute lung rejection
      episode in a severely infected patient, assuming that its mechanism of action is
      an immunomodulation rather than an actual immunosuppression. RESULTS: Three weeks
      after the simultaneous beginning of antiinfectious and extracorporeal
      photochemotherapy treatments, the patient improved clinically. Acute lung
      rejection was no longer detectable histologically 4 weeks after the beginning of
      extracorporeal photochemotherapy. Twenty-two months after the beginning of
      extracorporeal photochemotherapy (47 months after transplantation), the patient
      was living a normal life. CONCLUSIONS: We believe this treatment may be
      considered for further studies not only in acute lung rejection therapy when
      intensive immunosuppression is contraindicated but also as a means of rejection
      prevention.

PMID- 7578194
TI  - Successful transplantation of a donor heart with prior non-Q-wave myocardial
      infarction.

PMID- 7578198
TI  - The team approach to cleft and craniofacial disorders--the down side.

PMID- 7578197
TI  - Grade 2 cellular heart rejection: does it exist?: Yes!

PMID- 7578196
TI  - Effects of deoxyspergualin on bronchial anastomosis healing in canine pulmonary
      allografts.

PMID- 7578195
TI  - Flow-volume loop contours after single lung transplantation.

PMID- 7578199
TI  - Wound healing in beagle dogs after palatal repair without denudation of bone.
AB  - The connection of scar tissue to palatal bone by Sharpey's fibers, after cleft
      palate surgery, might lead to maxillary growth inhibition. The aim of this study,
      in beagle dogs, was to investigate the possibility of preventing the development
      of Sharpey's fibers by means of a modified surgical technique. In group 1,
      palatal repair according to von Langenbeck, was simulated. In group 2, palatal
      surgery was performed using a new partially split flap technique. The palates
      were histologically evaluated 12 weeks after surgery and compared with a control
      group. In group 1, the scar tissue was firmly attached to bundle bone by means of
      Sharpey's fibers. In group 2 and in the control group, this kind of attachment
      was not found; the bone was of the lamellar type. The partially split flap
      technique had led to the development of vaguely demarcated scar tissue and it had
      prevented, to a large extent, development of Sharpey's fibers.

PMID- 7578200
TI  - Effects of gravity on velopharyngeal muscle activity during speech.
AB  - Assessment of the role of gravitational forces in the motor control of the
      velopharyngeal mechanism was the focus of this study. Specifically, the effect of
      gravity on activation levels of the levator veli palatini and palatoglossus
      muscles was assessed. Nineteen volunteers repeated a CV syllable in upright and
      supine body positions. Overall, lower peak activation levels of levator veli
      palatini were observed in the supine body position. The results suggest that less
      muscle activity was seen in the levator veli palatini in the supine body posture,
      where gravitational effects worked in the same direction (i.e., toward closure).
      No statistically significant group effects were seen in muscle activation levels
      of palatoglossus across the two body postures, although clear gravity effects
      were observed in some subjects. The implications of these findings from a speech
      motor control perspective are discussed in relation to normal and disordered
      velopharyngeal function.

PMID- 7578201
TI  - Levator veli palatini muscle activity in relation to intraoral air pressure
      variation in cleft palate subjects.
AB  - A comparison of the ranges of levator veli palatini EMG activity for speech
      versus a nonspeech task for subjects with cleft palate was the focus of this
      study. EMG values are also compared with subjects without cleft palate obtained
      in a previous study. Hooked-wire electrodes were inserted into the levator muscle
      of five adult subjects with cleft palate exhibiting mild hypernasality. Intraoral
      air pressure was measured concurrently. A blowing task was used to determine the
      subject's operating range for the levator muscle. Both the nonspeech and speech
      tasks were designed to sample the widest possible ranges of levator EMG activity.
      It was found that the subjects with cleft palate used a relatively high
      activation level for the levator muscle during speech, in relation to their total
      activation range, compared with the subjects without cleft palate. Implications
      are discussed in relation to possible anatomic and physiologic differences for
      cleft palate subjects compared to normal.

PMID- 7578203
TI  - Monitoring nasal and oral airway patency.
AB  - The hypothesis that upper airway breathing behaviors generally follow the rules
      of a physiologic regulating system implies the existence of sensors that monitor
      the airway environment. The purpose of this study was to assess the sensitivity
      of the monitoring system to sudden changes in airway patency in healthy, adult
      subjects. An instrument capable of changing airway dimensions in about 10 ms was
      used to assess psychophysical recognition and physiologic responses to sudden
      changes in airway size. Our results indicate that psychophysical recognition of
      change in patency occurred at a mean constriction area of 0.31 cm2. These
      findings suggest that recognition of change in airway size occurs well before the
      airway becomes flow-limiting or severely obstructed.

PMID- 7578202
TI  - Oral air pressure and nasal air flow rate on levator veli palatini muscle
      activity in patients wearing a speech appliance.
AB  - This study was designed to determine if levator veli palatini muscle activity can
      be elicited by simultaneous changes in oral air pressure and nasal air flow when
      a speech appliance is in place. The speech appliances routinely worn by 15
      subjects were each modified experimentally by drilling a hole in the vertical
      center of the pharyngeal bulb. The air flow rate into the nasal cavity through
      the opening in the bulb was altered by changing the circular area of the opening
      in the bulb from the occluded condition (Condition I), to circular area of 12.6
      mm2 (4 mm in diameter; Condition II), and then to 38.5 mm2 (7 mm in diameter;
      Condition III). Electromyographic activity was measured from the levator veli
      palatini muscle with changes in nasal air flow rate and oral air pressure.
      Levator veli palatini muscle activity was correlated with changes in nasal air
      flow and oral air pressure. Increases in levator veli palatini muscle activity
      were associated with increases in nasal air flow rate compared to oral air
      pressure changes. The results indicated that aerodynamic variables of nasal air
      flow and oral air pressure might be involved in the neural control of speech
      production in individuals wearing a speech appliance, even if the subjects
      exhibit velopharyngeal incompetence without using a speech appliance. Also, the
      stimulating effect of bulb reduction therapy on velopharyngeal function might be
      achieved through the change in aerodynamic variables in association with the bulb
      reduction.

PMID- 7578204
TI  - Quantitative evaluation of craniofacial growth in the third trimester human.
AB  - A detailed understanding of fetal craniofacial growth is necessary for
      understanding the mechanisms underlying the growth process and how altered growth
      patterns may give rise to specific craniofacial anomalies. Although descriptive
      studies of human fetal craniofacial growth are abundant, quantitative studies are
      less common; most employ only lateral cephalograms or tracings of sectioned
      specimens. In this study, we compared growth rates in the individual bones of the
      facial and basicranial regions in a large sample of spontaneously aborted, third
      trimester fetuses. Growth in the individual dimensions of most bones is not
      significantly different from isometry when compared with body weight, but
      comparisons of dimensions within bones show clear changes in shape. In
      particular, the mandible is characterized by a deepening of the corpus, probably
      in association with development of the teeth. The maxilla also shows a relatively
      rapid height increase associated with dental development. The temporal bone grows
      faster in superoinferior height as opposed to anteroposterior width. The lateral
      and inferior margins of the zygomatic bone grow faster than the orbital margin.
      The basioccipital bone, cited in radiographic studies as growing substantially
      slower than the facial region, actually changes in shape more rapidly than any
      other skeletal component examined in this study, with widths growing much faster
      than lengths. Our findings demonstrate that craniofacial development in the third
      trimester is characterized by localized variation in the rate of growth within
      and between individual skeletal components, and that gross characterizations of
      regional rates of growth inadequately characterize craniofacial development.

PMID- 7578205
TI  - OMENS-Plus: analysis of craniofacial and extracraniofacial anomalies in
      hemifacial microsomia.
AB  - This review of 121 patients with hemifacial microsomia (HFM) revealed that 67
      (55.4%) had extracraniofacial anomalies. Sixteen patients (13%) had one
      extracraniofacial anomaly and 51 patients (42.4%) had anomalies of multiple organ
      systems. There was no gender or side predominance in the cohort with the HFM
      "expanded spectrum." Central nervous system (CNS), cardiac, and skeletal
      anomalies were "associated" (i.e., had frequencies of 10% or more). Pulmonary,
      gastrointestinal, and renal deformities were equivocally associated. Statistical
      analysis indicated significant associations between several orbital, mandibular,
      ear, neural, and soft tissue (OMENS) variables and extracraniofacial anomalies.
      Patients with extracraniofacial structural defects had higher OMENS grades for
      individual craniofacial anatomic categories. Furthermore, patients with expanded
      spectrum had higher total OMENS scores. The frequency of cardiac anomalies (26%)
      supports the model of neural crest involvement in the pathogenesis of both
      hemifacial microsomia and conotruncal defects. The majority of the heart defects
      in this study were of either the outflow or septal type. We propose that the
      OMENS classification system for craniofacial anomalies of HFM be expanded to
      OMENS-Plus (+) to designate the presence of associated extracraniofacial
      anomalies.

PMID- 7578206
TI  - Skull morphology affected by different sleep positions in infancy.
AB  - In infancy, prior to cranial suture and fontanel calcification, the craniofacial
      skeleton can be easily deformed by an externally exerted force. In this study,
      the relationship between the sleep position and skull morphology was
      investigated. A group of 81 cleft lip and/or palate infants without other
      systemic anomalies was first seen in the craniofacial center at approximately 1
      month of age. The sleep position of each infant was recorded as supine, prone, or
      mixed type. The body and skull growth were longitudinally measured at 1, 3, and 6
      months of age. Infants sleeping in the supine sleep position tended to have a
      wider head width, shorter head length, and a larger cephalic index by 6 months of
      age. The opposite phenomena were observed in the prone sleep group. The mixed
      sleep group tended to have head width, head length, and cephalic index between
      those of the supine sleep group and the prone sleep group. During the first 3
      months of life, the sleep position could mold the skull primarily in the
      dimension of head width. In conclusion, the supine sleep position may promote
      brachycephaly and the prone sleep position dolichocephaly.

PMID- 7578207
TI  - Cleft width and secondary alveolar bone graft success.
AB  - Fifty-six cleft sites were reviewed prior to alveolar bone grafting and
      subsequently evaluated for graft success using study models, periapical and
      occlusal radiographs from the Lancaster Cleft Palate Clinic. All patients in this
      sample had presurgical orthodontics to expand and align the maxillary arch prior
      to alveolar bone grafting. Ninety-five percent of the grafts were done using
      iliac crest, the remaining 5% were cranial grafts. The alveolar bone grafting
      technique used was as described by Boyne and Sands (1972, 1976). Cleft width was
      measured on a radiograph taken no more than 1 month preoperatively, following the
      completion of all orthodontic expansion. Cleft width was determined by inspection
      at its narrowest point. A distortion correction was attempted by determining the
      ratio of the radiographic width of the maxillary central incisor adjacent to the
      cleft compared with the actual width of this tooth measured on study models. The
      radiographic cleft width was then multiplied by this factor to approximate true
      cleft width. Alveolar contour was measured at least 6 months postoperatively
      using ratios of actual bone heights measured at the mesial, middle, and distal
      margin of the previous cleft compared with root length of adjacent teeth. This
      was to eliminate the radiographic distortion factors of foreshortening and
      elongation. Regression analysis was carried out to see if there was a correlation
      between preoperative cleft width and eventual success of the graft as measured on
      postsurgical radiographs. The success rate for achieving a bony bridge across the
      cleft was 91%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578208
TI  - Skeletal asymmetries of the nasomaxillary complex in noncleft and postsurgical
      unilateral cleft lip and palate individuals.
AB  - Asymmetries in the nasomaxillary skeleton are very common in individuals with
      unilateral cleft lip and palate. The purpose of this study was to retrospectively
      evaluate postsurgical asymmetries of the nasomaxillary skeleton in unilateral
      cleft lip and palate patients. Included in this study were 36 complete cleft lip
      and palate subjects, along with 36 noncleft (control) subjects. Skeletal
      asymmetry, deviations of the anterior nasal spine, and the premaxillary area were
      compared by chronologic age and skeletal maturation in cleft subjects and
      controls. Comparison between cleft and control cases was assessed. Results
      indicated that skeletal asymmetry in unilateral clefts and controls peaks during
      the pubertal growth spurt. The anterior nasal spine and nasal septum always tend
      to deviate toward the noncleft side of the nasal cavity, although individual
      variation exists. Cleft subjects were found to be more asymmetric than noncleft
      subjects to a statistically significant degree.

PMID- 7578209
TI  - Landmark positioning on maxilla of cleft lip and palate infant--a reality?
AB  - In this study, we tested the precision of landmark positioning for a set of
      landmarks that can be used for the edentulous cleft lip and palate maxilla of the
      infant, by analyzing intraobserver and interobserver repositioning and measuring
      on a series of 121 (unilateral and bilateral) study casts. To date, no data on
      interobserver and only minimal data on intraobserver reproducibility are
      available. We found intraobserver reproducibility acceptable with total
      measurement errors ranging from 0.51 to 1.54 mm. Interobserver reproducibility
      was only slightly less with total measurement errors ranging from 0.63 to 1.57
      mm. Total measurement errors were found to be relatively high for some variables.
      Both the intra- and interobserver analyses show insight into expected precision
      of landmark positioning during placement of these points on casts. A learning
      effect for precise positioning has been demonstrated in both analyses. The points
      with the highest precision overall are Q and Q', followed by the linear
      measurements PL and P'L'. Quality of regular study casts (impressions) is an
      important factor, with room for improvement. Reproducible landmark positioning on
      the cleft lip and palate infant's maxilla, can only be a reality if the quality
      of the cast is optimal and the investigator is experienced. Intraobserver and
      interobserver reproducibility are in the same range, which justifies the
      comparison of results from different studies and relieves future investigators of
      the need to have all measurements within a study conducted by the same
      investigator. Aspects of the biologic meaning of landmarks are also discussed.

PMID- 7578210
TI  - Prosthodontic abutment in four patients with unilateral cleft lip and palate.
AB  - An examination of the relation between the number of teeth used as the abutment
      of a fixed prosthesis and the increase of the functional loading capacity of the
      upper jaw was conducted in four male patients with unilateral cleft lip and
      palate (age range, 19 to 21 years). This was measured at the maximum biting force
      at each two teeth adjacent to the cleft under various splint extension conditions
      and compared with that in the nonsplint condition. In all subjects, the maximum
      biting force under every splinted condition was significantly increased compared
      with the nonsplint condition. The increase was proportional to the number of
      teeth included in the splinting. Results indicated that two teeth should be used
      in each segment in the abutment of the splint across the cleft in order to
      increase the functional loading capability of the upper jaw comparable to that of
      the lower jaw. The results also indicated that inclusion of more than two teeth
      has no further advantageous effect on the functional loading capability.

PMID- 7578212
TI  - Molecular cloning and sequencing of cytochrome c' from the phototrophic purple
      sulfur bacterium Chromatium vinosum.
AB  - The gene for cytochrome c' from Chromatium vinosum was cloned from a HindIII-SalI
      digest of genomic DNA. A 1.4 kbp fragment containing the gene was sequenced in
      both directions using the Sanger dideoxy method. The cytochrome c' gene codes for
      a 154-residue peptide, of which the last 131 amino acids match the previously
      determined sequence of the protein. The remaining 23 residues represent a signal
      sequence that is cleaved from the polypeptide upon translocation to the
      periplasmic space. An additional open reading frame on the other strand of the
      fragment codes for a peptide that contains four regions that are homologous to
      corresponding regions of the cytochrome b-type subunit of several Ni-Fe
      hydrogenases.

PMID- 7578211
TI  - Cytochrome b-558 alpha-subunit cloning and expression in rat aortic smooth muscle
      cells.
AB  - Recent studies have shown that the NADPH oxidase participates in the generation
      of superoxide anion in non-phagocytic cells. Here we report the isolation and
      nucleotide sequence of a cDNA for the cytochrome b-558 alpha-subunit of the NADPH
      oxidase in rat vascular smooth muscle cells (VSMCs). The coding region of the
      cDNA was 93% homologous to mouse and 81% to human in nucleotide sequence and 96%
      homologous to mouse and 89% to human in the deduced amino acid sequence. Our
      results provide a tool with which to explore the mechanism of superoxide anion
      generation in rat VSMCs and other non-phagocytic cells.

PMID- 7578213
TI  - Reconstitution of membrane proteins into liposomes: application to energy
      transducing membrane proteins.

PMID- 7578214
TI  - NADPH oxidase activity of cytochrome P-450 BM3 and its constituent reductase
      domain.
AB  - Cytochrome P-450 BM3 from Bacillus megaterium catalyses NADPH oxidation in the
      absence of added substrate. This activity is also associated with the
      independently expressed flavin-containing reductase domain of the protein. The
      rates of these activities are more than two orders of magnitude lower than those
      in the presence of fatty acid P-450 substrates or artificial electron acceptors.
      Electrons derived from NADPH in this fashion are transferred onto oxygen,
      generating superoxide (O2-) anions. The formation of these active oxygen species
      is detectable by luminometry and the chemiluminescence can be inhibited through
      the addition of superoxide dismutase (but not catalase). This activity is
      reminiscent of the microbicidal NADPH oxidase activity associated with
      neutrophils and other leukocyte blood cell types. Diphenyliodonium, a potent
      inhibitor of the neutrophil NADPH oxidase, effectively inhibits fatty acid
      hydroxylase and electron transferase activities catalysed by P-450 BM3 and its
      reductase domain. CD studies on the native and NADPH-reduced P-450 BM3 and BM3
      reductase indicate that no secondary structural alteration is caused by pre
      incubation with the reductant. Therefore, the previously recognised reversible
      time-dependent inactivation of P-450 BM3 by NADPH may be attributed to the NADPH
      oxidase activity associated with the reductase domain of the enzyme.

PMID- 7578215
TI  - Analysis of time-dependent change of Escherichia coli F1-ATPase activity and its
      relationship with apparent negative cooperativity.
AB  - Except for the case of gradual activation of EF1 (F1-ATPase from Escherichia
      coli) caused by the dissociation of the epsilon subunit [Laget, P. P. and Smith,
      J. B. (1979) Arch. Biochem. Biophys. 197, 83-89], EF1 has long been thought not
      to show a time-dependent change in activity [Senior, A.E. et al. (1992) Arch.
      Biochem. Biophys. 297, 340-344]. Here, we report the time-dependent inactivation
      and activation of EF1, which are apparently similar to those of mitochondrial F1
      ATPases [Vasilyeva, E.A. et al. (1982) Biochem. J. 202, 15-23]. Analysis of these
      changes as a function of ATP concentrations in relation to negative cooperativity
      revealed that the initial inactivation phase was attributable to the decrease in
      the Vmax associated with the low Km (around 10 microM), and the following
      activation, probably due to the dissociation of the epsilon subunit, corresponded
      to the increase in the Vmax associated with the high Km (in the order of 100
      microM). Thus, the time-dependent change in EF1 activity is closely related to
      the apparent negative cooperativity (multiple Km values) of ATP hydrolysis.

PMID- 7578217
TI  - The mechanism of hydride transfer between NADH and 3-acetylpyridine adenine
      dinucleotide by the pyridine nucleotide transhydrogenase of Escherichia coli.
AB  - The pyridine nucleotide transhydrogenase of Escherichia coli catalyzes the
      reversible transfer of hydride ion equivalents between NAD+ and NADP+ coupled to
      translocation of protons across the cytoplasmic membrane. Recently,
      transhydrogenation of 3-acetylpyridine adenine dinucleotide (AcPyAD+), an analog
      of NAD+, by NADH has been described using a solubilized preparation of E. coli
      transhydrogenase [Hutton, M., Day, J.M., Bizouarn, T., and Jackson, J.B. (1994)
      Eur. J. Biochem. 219, 1041-1051]. This reaction depended on the presence of
      NADP(H). We show that (a) this reaction did not require NADP(H) at pH 6 in
      contrast to pH 8; (b) the reaction occurred at pH 8 in the absence of NADP(H) in
      the mutant beta H91K and in a mutant in which six amino acids of the carboxy
      terminus of the alpha subunit had been deleted; (c) the mutant transhydrogenases
      contained bound NADP+ and were in a conformation in which the beta subunit was
      digestible by trypsin; (d) the conformation of the beta subunit of the wild-type
      enzyme was made susceptible to trypsin digestion by NADP(H) or by placing the
      enzyme at pH 6 in the absence of NADP(H). It is concluded that reduction of
      AcPyAD+ by NADH does not involve NADPH as an intermediate and that the role of
      NADP(H) in this reaction at pH 8 is to cause the transhydrogenase to adopt a
      conformation favouring transhydrogenation between NADH and AcPyAD+.

PMID- 7578216
TI  - Stimulation of oxidative phosphorylation by electrophoretic K+ entry associated
      to electroneutral K+/H+ exchange in yeast mitochondria.
AB  - The effect of the addition of KCl, at constant osmolarity, was investigated on
      oxidative phosphorylation in isolated yeast mitochondria. KCl stimulated both
      respiration and ATP synthesis rates without changing the ATP/O ratio. KCl did not
      change the relationships between respiration rates and the protonmotive force.
      Since the K+/H+ exchange activity was active under these conditions, the
      stimulatory effect of respiration could be explained by the net proton entry
      caused by the electrophoretic K+ entry/electroneutral K+/H+ exchange cycle. On
      the other hand, K+ entry stimulated phosphate accumulation and transport under
      non-phosphorylating conditions and decreased the kinetic control by phosphate
      transport under phosphorylating conditions. Additionally, the stimulation of ATP
      synthesis strongly depended on the activity of phosphate transport. Taken
      together, these data showed that electrophoretic K(+)-entry and electroneutral
      K+/H+ exchange occurred in phosphorylating yeast mitochondria but did not promote
      any uncoupling between respiration and ATP synthesis.

PMID- 7578218
TI  - Cyclic reactions catalysed by detergent-dispersed and reconstituted
      transhydrogenase from beef-heart mitochondria; implications for the mechanism of
      proton translocation.
AB  - Transhydrogenase from beef-heart mitochondria was solubilised with Triton X-100
      and purified by column chromatography. The detergent-dispersed enzyme catalysed
      the reduction of acetylpyridine adenine dinucleotide (AcPdAD+) by NADH, but only
      in the presence of NADP+. Experiments showed that this reaction was cyclic;
      NADP(H), whilst remaining bound to the enzyme, was alternately reduced by NADH
      and oxidised by AcPdAD+. A period of incubation of the enzyme with NADPH at pH
      6.0 led to inhibition of the simple transhydrogenation reaction between AcPdAD+
      and NADPH. However, after such treatment, transhydrogenase acquired the ability
      to catalyse the (NADPH-dependent) reduction of AcPdAD+ by NADH. It is suggested
      that this is a similar cycle to the one described above. Evidently, the binding
      affinity for NADP+ increases as a consequence of the inhibition process resulting
      from prolonged incubation with NADPH. The pH dependences of simple and cyclic
      transhydrogenation reactions are described. Though more complex than those in
      Escherichia coli transhydrogenase, they are consistent with the view [Hutton, M.,
      Day, J.M., Bizouarn, T. and Jackson, J.B. (1994) Eur. J. Biochem. 219, 1041-1051]
      that, also in the mitochondrial enzyme, binding and release of NADP+ and NADPH
      are accompanied by binding and release of a proton. The enzyme was successfully
      reconstituted into liposomes by a cholate dilution procedure. The proteoliposomes
      catalysed cyclic NADPH-dependent reduction of AcPdAD+ by NADH only when they were
      tightly coupled. However, they catalysed cyclic NADP(+)-dependent reduction of
      AcPdAD+ by NADH only when they were uncoupled eg. by addition of carbonylcyanide
      p-trifluoromethoxyphenyl hydrazone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578219
TI  - The 2Fe2S centres of the 2-oxo-1,2-dihydroquinoline 8-monooxygenase from
      Pseudomonas putida 86 studied by EPR spectroscopy.
AB  - The 2-oxo-1,2-dihydroquinoline 8-monooxygenase from Pseudomonas putida 86
      comprises two components with four redox active sites necessary for activity. We
      present an EPR characterization of the iron-sulfur centres in the purified
      reductase and oxygenase component of this novel enzyme system. The oxygenase
      component was identified as a Rieske [2Fe2S] protein on the basis of its
      characteristic EPR spectrum with gz,y,x = 2.01, 1.91, 1.76 and gav = 1.893. The
      reductase component, an iron-sulfur flavoprotein, contained a [2Fe2S] cluster
      with gz,y,x = 2.03, 1.94, 1.89 and the average g-value (gav) of 1.953, typical of
      a ferredoxin-type centre. In redox titrations at pH 7, the midpoint potentials
      were determined to be -180 mV +/- 30 mV and -100 mV +/- 10 mV for the reductase
      and oxygenase component, respectively. A detailed comparison to other
      multicomponent enzyme systems is presented pointing out the EPR and redox
      properties of the FeS centres involved.

PMID- 7578220
TI  - Does the sulfhydryl or the adenine moiety of CoA enhance firefly luciferase
      activity?
AB  - Light production by firefly luciferase is limited by product release resulting in
      flash kinetics. Several compounds (CoA, PPi, and nucleotides) transform the flash
      form of light production into continuous light production. The sulfhydryl group
      of CoA is required; however, since nucleotides are also active, at least two
      mechanisms (sites) must exist.

PMID- 7578221
TI  - Amino-acid sequence of rat liver kynureninase.
AB  - Amino-acid sequence of kynureninase purified from rat liver cytosol was
      determined by an amino-acid sequencer. The enzyme was degraded to small peptides
      with cyanogen bromide, TPCK-trypsin, endoproteinase Glu-C, lysyl endoprotease and
      alpha-chymotrypsin. The enzyme subunit consisted of 464 amino acids, and the
      molecular weight of subunit was determined to be 52,510. The coenzyme pyridoxal
      phosphate-binding residue was lysine of which position was 276, and the N
      terminal residue was N-acetylmethionine. The homology search between this enzyme
      and the other pyridoxal phosphate-dependent enzymes showed that kynureninase was
      similar to mitochondrial aspartate aminotransferase, and also to cystathionine
      gamma-synthase and gamma-lyase to a lesser extent.

PMID- 7578222
TI  - Primary structure of a constituent polypeptide chain of the chlorocruorin from
      Sabellastarte indica.
AB  - A 16 kDa polypeptide chain (chain E) was isolated from the giant extracellular
      chlorocruorin from the polychaete Sabellastarte indica by reverse-phase
      chromatography, and the N-terminal 19 amino-acid residues was determined by an
      automated protein sequencer. The cDNA of Sabellastarte chain E was amplified by
      polymerase chain reaction (PCR), and the complete nucleotide sequence of 1205 bp
      was determined. The open reading frame is 498 nucleotides in length and encodes a
      protein with 165 amino-acid residues. Comparison of the cDNA-derived amino-acid
      sequence with the protein sequence shows that Sabellastarte chain E has a signal
      peptide of 16 residues at the N-terminus, the mature protein consisting of 149
      amino-acid residues with a calculated molecular mass of 16636 Da. The amino-acid
      sequence of Sabellastarte chain E shows 42-49% sequence identity with the
      corresponding chains of the giant hemoglobins from Tylorrhynchus (polychaete,
      Annelida), Lumbricus (oligochaete, Annelida), Lamellibrachia (Vestimentifera) and
      Oligobrachia (Pogonophora). Thus, we conclude that chlorocruorin with
      chlorocruorohaem falls into the 'hemoglobin/myoglobin family'. This is the first
      complete sequence of a globin polypeptide chain of a chlorocruorin.

PMID- 7578223
TI  - The removal of 2-oxoacyl residues from the N-terminus of peptides and cystatin in
      non-denaturing conditions.
AB  - The N-terminal residue of a protein or peptide may be converted into a 2-oxoacyl
      group by non-enzymic transamination. This group may then be removed, to obtain
      the peptide chain shortened by one residue, by treatment with phenylene-1,2
      diamine. Hitherto this scission has required a pH of 4-5, but we find that the
      reaction will proceed well at pH 7 in the presence of concentrated phosphate
      buffer. We describe a method using reverse-phase HPLC for determining the extent
      of scission in model peptides; this method also allows products to be isolated
      and identified. The new scission conditions have been tested by removing the N
      terminal residue from cystatin, an inhibitor of cysteine peptidases; electrospray
      mass spectrometry was used to assess how this protein reacted.

PMID- 7578224
TI  - Arginine-239 in the beta subunit is at or near the active site of bovine pyruvate
      dehydrogenase.
AB  - We have modified bovine pyruvate dehydrogenase (E1), the first catalytic
      component of the pyruvate dehydrogenase complex, with pyreneglyoxal. Treatment of
      E1 with pyreneglyoxal resulted in the loss of enzyme activity. Pyruvate plus
      thiamin pyrophosphate (TPP) afforded approximately 80% protection against this
      inactivation and protected two arginine residues per mol of E1 tetramer (alpha 2
      beta 2) from modification. Circular dichroism spectral analysis indicated absence
      of any gross structural changes in the enzyme as a result of modification.
      Comparison of the peptide maps, monitored at 345 nm of unprotected and pyruvate
      plus TPP protected E1s after V8 digestion revealed that a peptide in the
      protected enzyme was labeled by pyreneglyoxal to a lesser extent than its
      counterpart in the unprotected enzyme. Sequence analysis of the peptide
      demonstrated that it corresponded precisely to amino-acid residues 235 to 246 in
      the human E1 beta sequence, with arginine residues at positions 239 and 242.
      Since Arg-239 is conserved in the beta-subunit of all presently known sequences
      of the pyruvate dehydrogenase complex and branched-chain alpha-keto acid
      dehydrogenase complex, it is strongly suggested that Arg-239 in the human E1 beta
      sequence is at or near the active site of bovine E1.

PMID- 7578225
TI  - Structural study of the glycosylated and unglycosylated forms of a genetic
      variant of human serum albumin (63 Asp-->Asn).
AB  - A genetic variant of human serum albumin (alloalbumin) exhibited atypical
      electrophoretic mobility and chromatographic behavior apparently because of the
      effect of a point substitution on the molecular conformation. Three forms of
      albumin were isolated by DEAE HPLC chromatography: normal albumin, and two
      variant forms V1 and V2. The point substitution (Asp-63-->Asn) generated a
      canonical tripeptide acceptor sequence for glycosylation with an N-linked
      oligosaccharide (Asn-Lys-Ser). Neuraminidase digestion followed by
      electrophoresis showed that the V2 variant form was glycosylated and the V1 form
      was not. Time-of-flight mass spectrometry yielded a molecular weight of about
      2000 for the carbohydrate. Structural analysis of the carbohydrate was done by
      chromatographic comparison of the pyridylaminated derivatives with standards and
      was confirmed by proton NMR of the three pronase glycopeptides and of the
      pyridylaminated oligosaccharide. The oligosaccharide had a complex biantennary
      structure with two sialic acid residues. In normal albumin Asp-63 is exposed and
      is adjacent to the first disulfide bond, Cys-62-->Cys-53. The apparent effect on
      molecular conformation resulting in incomplete glycosylation and atypical
      electrophoretic mobility suggests that glycosylation may interfere with disulfide
      bond formation at this site.

PMID- 7578226
TI  - Biochemical characterization of the melanogenic system in the eye of adult
      rodents.
AB  - The melanogenic activities in the eye of the adult gerbil (Meriones unguiculatus)
      have been investigated and compared to those found in the B16 mouse melanoma
      model. Eye extracts contain tyrosine hydroxylase, DOPA oxidase, DOPAchrome
      tautomerase and DHICA oxidase activities. The subcellular distribution of these
      activities was investigated by differential centrifugation and detergent
      solubilization of the particulate fractions. The distribution pattern closely
      resembled the one found for mouse melanoma, with a higher percentage of activity
      associated to the particulate fractions but a substantial proportion in the
      cytosolic fraction. The tyrosine hydroxylase activity was characterized by a KM
      of 62 microM for L-tyrosine and a stringent requirement for the co-factor L-DOPA
      (Ka 10.3 microM). The KM for L-DOPA was 0.41 mM. The sensitivity of the eye and
      mouse melanoma tyrosinase activity to a variety of substrate analogs and metal
      chelators was found to be identical. In keeping with these kinetic similarities,
      eye tyrosinase displayed some structural properties resembling those of the
      melanoma enzyme. The molecular weight of the enzyme, determined by SDS-PAGE and
      DOPA oxidase activity stain, was 75 kDa for the eye enzyme and 66.2 kDa for
      melanoma tyrosinase, and both enzymes were apparently dimeric in non ionic
      detergent solution. Immunoprecipitation with specific antibodies proved that at
      least 80% of the total tyrosinase activity could be immunoprecipitated with the
      specific anti-tyrosinase antibody alpha PEP7, while the anti-TRP-1 monoclonal
      antibody TMH-1 precipitated little, if any, tyrosinase activity. Taken together,
      these observations provide the first vis-a-vis comparison of an extracutaneous
      melanogenic system and the melanogenic system of melanoma. Our results prove
      that, at least in rodents, the melanogenic system in the eye is similar, but not
      identical, to the melanin biosynthesis machinery of epidermal melanocytes.

PMID- 7578227
TI  - NMR studies of the alpha-chymotrypsin-(R)-1-acetamido-2-(4-fluorophenyl)ethane-1
      boronic acid complex at pH 7.
AB  - The interaction of (R)-1-acetamido-2-(4-fluorophenyl)ethane-1-boronic acid with
      alpha-chymotrypsin at pH 7 was studied by a variety of fluorine and proton NMR
      experiments and the results compared to observations made at pH 4. It was
      demonstrated that this compound forms a complex with a 1:1 stoichiometry at pH 7;
      proton NMR indicates that the boronic acid likely is coordinated to the serine
      195 residue at the active site. Analysis of fluorine T1 relaxation behavior and
      19F(1H) NOE data shows that the rate constant for dissociation of the complex is
      4.7 s-1, somewhat faster than is observed at pH 4. The data analysis and the
      results of two-dimensional 19F(1H) NOE experiments show that interactions between
      the fluoroaromatic ring of the inhibitor and the enzyme are weaker at the higher
      pH value, although the motion of the fluoroaromatic ring within the complex
      appears to be just as restricted as is the case at pH 4.

PMID- 7578228
TI  - The C-terminal region, Arg201-Gln209, of glutathione S-transferase P contributes
      to stability of the active-site conformation.
AB  - The C-terminal region of rat glutathione S-transferase P (GST-P) was deleted by
      either carboxypeptidase (CPase) A and B or site-specific truncation to evaluate
      the role of the region in the catalytic mechanism. The C-terminal sequence from
      the 201st to 209th amino-acid residues is Arg-Pro-Ile-Asn-Gly-Asn-Gly-Lys-Gln.
      When seven of the C-terminal amino-acid residues from the C-terminus were removed
      by the CPases, the catalytic activity decreased in parallel with the amino-acid
      removal, amounting to less than 5% of that of the wild-type GST-P. On the other
      hand, a decrease of the catalytic activity was observed in a different manner
      when the C-terminal sequence was site-specifically truncated. The VmaxGSH/KmGSH
      values of the mutants withthree (GSTd207-209), four (GSTd206-209) and seven
      (GSTd203-209) C-terminal amino-acid residues deleted, were comparable or similar
      to that of the wild-type GST-P, whereas those of five (GSTd205-209), six (GSTd204
      209), and eight (GSTd202-209) amino-acid residue-truncated mutants decreased to
      43%, 40%, and 19% of that of the wild-type GST-P, respectively. Similar results
      were obtained as for VmaxCDNB/KmCDNB. The nine amino-acid residue-truncated
      mutant showed no catalytic activity. Heat treatment at 50 degrees C for 5 min had
      little effect on the catalytic activities of the wild-type GST-P and GSTd204-209,
      whereas those of GSTd207-209, GSTd206-209, GSTd203-209 and GSTd202-209 decreased
      to 22%, 27%, 18% and 10%, respectively, compared to the catalytic activity of the
      non-treated enzymes. Considering these results, it is concluded that the C
      terminal region, Arg201-Gln209, has an important role in stabilizing the active
      site conformation.

PMID- 7578229
TI  - Modification with tetranitromethane of an essential tyrosine residue in uridine
      phosphorylase from Escherichia coli.
AB  - Treatment with tetranitromethane (TNM) rapidly and irreversibly inactivates
      uridine phosphorylase (UPase) from E. coli under mildly alkaline conditions.
      Modification of one of the four tyrosine residues decreases enzyme activity to
      10%, while modification of all tyrosines decreases it to 8%. The second-order
      rate constant for the inactivation is 1250 +/- 50 M-1 min-1 at pH 8.0. Phosphate
      (0.1 M) does not affect the inactivation rate, while 5 mM uridine, or uridine
      plus phosphate nearly completely protect the enzyme against inactivation. Free
      sulfhydryl groups of UPase are not oxidized by TNM. A single modified peptide was
      isolated from tryptic digest by reverse-phase HPLC. The mass to charge ratio and
      the sequence determined are consisted with modification of Tyr-169, which
      corresponds to tryptic peptide 169Tyr-Asp-Thr-Tyr-Ser-Gly-Arg175. Tyrosine
      nitration leads to a significant decrease in the pKa of the phenolic hydroxy
      group without significantly affecting enzyme structure. Comparison of the pH
      dependence of activity and inactivation by diethylpyrocarbonate for the native
      and modified UPase reveals interaction between the modified tyrosine residue and
      an essential histidine residue (Drabikowska, A.K. and Wozniak, G (1990) Biochem.
      J. 270, 319-323). It is suggested that Tyr-169 takes part in the stabilization of
      the imidazole ring of the essential histidine in UPase.

PMID- 7578230
TI  - Marked detergents effects on safranine T-mediated photo-induced electron transfer
      in cytochrome P-450 1A2.
AB  - Cytochrome P-450 accepts electrons from electron transfer proteins to facilitate
      monooxidation reactions. It is suggested that basic amino acids such as Lys and
      Arg on the P-450 molecular surface interact with acidic amino acids such as Glu
      and Asp of the electron transfer protein. Safranine T is a basic compound which
      mediates electron transfer with illumination. It was found with flash photolysis
      that an electron from photo-reduced safranine T quickly reaches the heme iron of
      cytochrome P-450 1A2 (P-450 1A2). The photo-induced reduction kinetics of P-450
      1A2 were analyzed by the Runge-Kutta method on the second order assumption. The
      electron-transfer rate constant from safranine T to P-450 1A2 was 2.1 x 10(6) M
      1s-1. The rate constant was remarkably increased up to 3.1 x 10(8) M-1s-1 by
      adding cholic acid, while that was drastically reduced down to 3.5 x 10(4) M-1s-1
      by adding Emulgen 913. The electron-transfer rate of a His163-Glu mutant, which
      has a 40 mV lower redox potential than that of the wild type, was the same as
      that of the wild type in the absence of the detergents, although the reduced
      fraction of the mutant was 30% lower than that of the wild type. The electron
      transfer rate of the mutant also changed significantly by adding the detergents
      in the same way as the wild type. Based on these results, together with optical
      absorbance and fluorescence data, we discuss the inter- and intramolecular
      electron-transfer mechanism of P-450 1A2.

PMID- 7578231
TI  - On the interaction of alpha-crystallin with unfolded proteins.
AB  - alpha-Crystallin, a major protein component of the lens, has chaperone-like
      properties whereby it prevents destabilised proteins from precipitating out of
      solution. It does so by forming a soluble high-molecular-weight (HMW) complex. A
      spectroscopic investigation of the HMW complex formed between a variety of
      unfolded proteins and bovine alpha-crystallin is presented in this paper. As
      monitored by fluorescence spectroscopy, a large amount of the hydrophobic probe,
      8-anilino-1-naphthalene sulfonate (ANS) binds to the HMW complex implying that
      the complexed proteins (alcohol dehydrogenase (ADH), gamma-crystallin and
      rhodanese) are bound in an unfolded, possibly molten-globule state. The
      interaction between the anionic surfactant, sodium dodecyl sulfate (SDS) and ADH
      at high temperatures gives rise to a similar large increase in ANS fluorescence
      to that for the complex between alpha-crystallin and ADH. SDS, like alpha
      crystallin, therefore complexes to proteins in their unfolded state leaving a
      large hydrophobic surface exposed to solvent. Unlike other chaperones (e.g.,
      GroEL, DnaK and SecB), alpha-crystallin does not interact with unfolded,
      hydrophobic but stable proteins (e.g., reduced and carboxymethylated alpha
      lactalbumin and alpha-casein). It is concluded that alpha-crystallin will only
      complex with proteins that are about to precipitate out of solution, i.e., ones
      that are severely compromised. 1H-NMR spectroscopy of the HMW complex formed
      between alpha-crystallin and gamma-crystallin indicates that the short C-terminal
      extension of alpha B-crystallin, but not that of alpha A-crystallin, has lost its
      flexibility in the complex implying that the former is involved in interactions
      with the unfolded gamma-crystallin molecule, possibly electrostatically via its
      two C-terminal lysine residues.

PMID- 7578232
TI  - Inactivation of a subtilisin in colloidal systems.
AB  - The aim of the present study is to establish the relation between the
      inactivation of the proteolytic enzyme Savinase and its adsorption at different
      types of solid-liquid interfaces. The loss of activity has been determined both
      in solution and in the presence of colloidal particles, which provide a surface
      area for adsorption of 25% of the enzyme population. Analysis of the remaining
      solution at different periods of incubation of the various systems shows that the
      intact protein is converted into autolytic degradation products at the expense of
      biological activity. The different particles, however, deactivate the enzymes to
      a different extent. Under the experimental conditions the half-life of the
      enzymatic activity in solution is 3.5 hours. In the presence of particles that
      have hydrophobic surface properties (teflon- or polystyrene latex) the half-life
      is reduced to 0.7 hours. On the contrary, hydrophilic silica particles stabilize
      the enzyme against autolysis as compared to the inactivation in solution.
      Polystyrene latex particles which are chemically grafted with short poly(ethylene
      oxide) chains ([EO]8) are, for steric reasons, also mild with respect to the
      reduction of enzymatic stability. It is thus concluded that the type of surface
      determines the mode in which the enzyme is adsorbed on a particle which, in turn,
      affects the autocatalytic rate.

PMID- 7578233
TI  - Stopped-flow kinetic and biophysical studies of membrane-associated D-lactate
      dehydrogenase of Escherichia coli.
AB  - The enzyme kinetics of the FAD-containing membrane-associated D-lactate
      dehydrogenase (D-LDH) of Escherichia coli have been investigated by stopped-flow
      spectroscopy. The reduction of D-LDH by the substrate, D-lactate, exhibits a two
      stage behavior as observed by the absorbance change for the enzyme-bound FAD. The
      fast stage with a maximum rate of 400 s-1 represents the rapid formation of the
      enzyme-substrate complex and the formation of the equilibrium between the
      oxidized and the reduced enzyme-substrate complexes. The slow stage, which occurs
      on the order of 0.36 s-1, represents the slow release of the product, pyruvate,
      from the reduced enzyme. The formation of a D-LDH semiquinone radical was not
      observed during the oxidation of D-lactate by D-LDH at 25 degrees C. However,
      during the subsequent electron transfer from the reduced enzyme to a nitroxide
      spin-label, a one-electron acceptor, an enzyme intermediate has been observed and
      identified by both optical and EPR spectroscopies as an anionic semiquinone.
      Results from 1H-NMR spectroscopic studies suggest the possible formation of a
      substrate carbanion when D-lactate is bound at the active site of D-LDH.

PMID- 7578234
TI  - Nature and environment of the sulfhydryls of membrane-associated D-lactate
      dehydrogenase of Escherichia coli.
AB  - Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoic acid), has been used to titrate D
      lactate dehydrogenase (D-LDH), a respiratory flavoenzyme of Escherichia coli. All
      six of the possible sulfhydryls titrate in the presence of 2% sodium
      dodecylsulfate, showing that D-lactate dehydrogenase does not contain any -S-S-
      bridges. In the native state, only two sulfhydryls are accessible in buffer and
      only one in the presence of lipid. Single-site mutations of each of the six
      cysteines of D-lactate dehydrogenase have been prepared. Each of the purified
      mutant proteins has full activity, demonstrating that an -SH group is not
      essential to the FAD-driven redox reaction. Ellman's titrations of the mutant
      proteins have led to the identification of cysteines 65, 146, 156, and 256 in the
      amino-terminal end as those containing the sulfhydryls that are not accessible in
      buffer or in buffer plus lipid. The cysteine at 422 is titrated only partially in
      buffer, while in buffer containing lipid, a necessary factor for full enzymatic
      activity, its sulfhydryl is inaccessible to the reagent. Cysteine 492 has been
      identified as containing the sulfhydryl that is accessible to the reagent under
      both conditions.

PMID- 7578235
TI  - Friction analysis of kinetic schemes: the friction coefficient.
AB  - Friction analysis is proposed as the application of general control analysis to
      single enzymes to describe the control of elementary kinetic steps on the overall
      catalytic rate. For each transition, a friction coefficient is defined that
      measures the sensitivity of the turnover rate to the free energy of the
      transition state complex of the transition. The latter is captured in a single
      property of the transition, termed friction, as the geometrical mean of the
      inverse of the forward and backward rate constants. By definition, the friction
      coefficient measures the relative change in the turnover rate in response to a
      small change in the friction. The friction coefficient is the sum of the flux
      control coefficients of the forward and backward rate constants from general
      control theory and measures the extent to which an elementary step is rate
      determining. Two basic rules apply to the friction coefficients: (i) the
      summation theorem states that summation of the friction coefficients over all the
      steps in a scheme results in a value of 1, and (ii) the group rule states that
      grouping of rate constants of similar transitions results in a friction
      coefficient for the group that is the sum of the friction coefficients of the
      individual steps in the group. The friction coefficients are derived for a number
      a kinetic schemes taking the rate equations as the starting point and both rules
      are demonstrated. In fully coupled systems the friction coefficients of
      individual steps lie between 0 and 1. In partially uncoupled systems the
      summation theorem applies to all the rates in the system, however, the summation
      of subsets of friction coefficients may exceed the value of one, implying
      negative values for other steps in the scheme. The values of individual friction
      coefficients lie between -1 and 1. The friction coefficient is redefined in a
      numerical treatment of the steady state of more complex enzymatic schemes.

PMID- 7578236
TI  - Variable-temperature study of the heme-reorientation process in equine myoglobin.
AB  - The redistribution of the initially-formed myoglobin heme-insertion isomers from
      the initially formed 50/50 mixture to the equilibrium ratio of 90/10 has long
      been assumed to occur by one of two mechanisms, both of which require the rupture
      of the heme iron-protein bond (La Mar, G.N., Toi, H. and Krishnamoorthi, K.
      (1984) J. Am. Chem. Soc. 106, 6395-6401). In this study we compared the use of
      nuclear magnetic resonance and optical spectroscopic techniques as methods for
      studying the reorientation of heme within myoglobin. We found that kinetics
      determinations of the heme insertion isomer redistribution process in Mb by
      optical spectroscopy are quantitatively compatible with the results obtained by
      nuclear magnetic resonance spectroscopy. A variable-temperature analysis for
      horse myoglobin using the optical method at pH 8.4 +/- 0.1 yielded the following
      activation energy parameters: delta H++ = 31 kcal/mol, delta S++ = 34 cal/mol per
      K, and delta G++21 degrees C = 21 kcal/mol. The value of delta G++ expected for
      complete dissociation of the heme from myoglobin can be estimated, from its
      dissociation constant and insertion rate, to be on the order of 23-27 kcal/mol
      under the same conditions as our determination. Therefore, although the mechanism
      for heme reorientation in Mb is likely non-dissociative, it has an activation
      energy which is not far from the lower bound expected for a complete
      dissociation/recombination mechanism. Our measured entropy of activation is not
      especially large, perhaps owing to a large contribution by the solvent.

PMID- 7578237
TI  - Resonance Raman study on the iron-sulfur centers of Desulfovibrio gigas aldehyde
      oxidoreductase.
AB  - Resonance Raman spectra of the molybdenum containing aldehyde oxidoreductase from
      Desulfovibrio gigas were recorded at liquid nitrogen temperature with various
      excitation wavelengths. The spectra indicate that all the iron atoms are
      organised in [2Fe-2S] type centers consistent with cysteine ligations. No
      vibrational modes involving molybdenum could be clearly identified. The features
      between 280 and 420 cm-1 are similar but different from those of typical plant
      ferredoxin-like [2Fe-2S] cluster. The data are consistent with the presence of a
      plant ferredoxin-like cluster (center I) and a unique [2Fe-2S] cluster (center
      II), as suggested by other spectroscopic studies. The Raman features of center II
      are different from those of other [2Fe-2S] clusters in proteins. In addition, a
      strong peak at ca. 683 cm-1, which is not present in other [2Fe-2S] clusters in
      proteins, was observed with purple excitation (406.7-413.1 nm). The peak is
      assigned to enhanced cysteinyl C-S stretching in center II, suggesting a novel
      geometry for this center.

PMID- 7578238
TI  - Molecular characterization of a Galactomyces geotrichum lipase, another member of
      the cholinesterase/lipase family.
AB  - Geotrichum candidum secretes several lipase isoenzymes, differing in their
      selectively towards esters of long chain fatty acids with a cis-9 double bond.
      One group shows an absolute selectively towards these fatty acid esters, the
      other group has a more relaxed specificity and will also hydrolyze other long
      chain fatty acid esters. Galactomyces geotrichum secrets a lipase that has the
      same specificity as the latter group. The corresponding lipase gene was cloned
      from Galactomyces geotrichum. From an alignment of our enzymes' primary structure
      with those of different strains of Geotrichum candidum, remarkable conservation
      is evident and it is not yet possible to identify residues/structures responsible
      for differences in fatty acid specificity. Comparison of the GCL/GGL family with
      a variety of lipases from other sources, indicated that they are more related to
      mammalian than microbial lipases.

PMID- 7578239
TI  - Conformation of polymyxin B analogs in DMSO from NMR spectra and molecular
      modeling.
AB  - The tertiary structures of two polymyxin analogues: [formula: see text] and
      [formula: see text] in DMSO, from solid-phase peptide synthesis and aerobic
      oxidation were determined from two-dimensional NMR spectra and distance geometry
      calculations followed by restrained molecular dynamics simulation. The backbone
      of peptide I had a rectangular shape stabilized by at least two hydrogen bonds
      and the hydrophilic side chains of five lysine residues, and the hydrophobic side
      chains of Phe and Leu resided at both sides to form an amphiphilic molecule. This
      amphiphilic structure of I is likely to interact with lipid A mainly via a
      hydrophobic interaction. Compared with I, peptide II, which lacks three N
      terminal amino-acid residues, exhibits neither amphiphilic property nor binding
      ability with lipid A.

PMID- 7578240
TI  - Purification and molecular characterization of lamb pregastric lipase.
AB  - Lamb pregastric lipase (LPGL) was purified from pharyngeal tissues. The
      purification procedure was based on an aqueous extract containing 0.7% Tween 80
      which was chromatographed on DEAE-cellulose anion-exchanger and adsorbed on HA
      Ultrogel followed by gel filtration on Ultrogel AcA-54. The final enzymatic
      preparation, where the overall activity recovery was 3%, showed a single protein
      band on SDS-PAGE with a molecular mass of 50 kDa. LPGL is a glycoprotein
      containing approx. 14% (w/w) of carbohydrate. Extensive deglycosylation using
      peptide N-glycosidase F yielded a protein with an apparent molecular mass of 43
      kDa. An uncontrolled proteolysis of LPGL during the purification lead to a 45 kDa
      form which was previously observed in human lysosomal acid lipase (HLAL) and
      rabbit gastric lipase (RGL). The labile bond X54-Leu55 was identified.
      Isoelectric focusing of LPGL reveals a major band corresponding to an isoelectric
      point of 4.8. The pure enzyme displayed specific activities of 950 U mg-1, 300 U
      mg-1 and 30 U mg-1 at pH 6.0, using tributyroylglycerol, trioctanoylglycerol and
      trioleoylglycerol as substrates, respectively. Using Western blot analysis, a
      cross-immunoreactivity of LPGL was observed with purified anti-human gastric
      lipase polyclonal antibodies. Determination of the amino-acid sequence of 62
      residues revealed a high degree of homology with other known preduodenal lipases.

PMID- 7578241
TI  - Characterization of multiple prohormone convertase PC1/3 transcripts in porcine
      ovary.
AB  - Overlapping cDNAs encoding porcine prohormone convertase, PC1/3, have been
      isolated from a pregnant sow ovary cDNA library using a mouse PC1/3 cDNA as a
      probe. Nucleotide sequence analysis of these cDNAs predicts a PC1/3 precursor
      protein of 753 amino acid residues, which shares an overall sequence homology of
      96, 92, and 92% with the human, rat, and mouse counterparts, respectively.
      Furthermore, five different polyadenylation sites have been observed. The
      utilization of these polyadenylation sites results in a length difference of 40
      440 bp in the 3' untranslated regions of the transcripts.

PMID- 7578242
TI  - Intragenic matrix attachment and DNA-protein interactions in the human X-linked
      Hprt gene.
AB  - To investigate the possible contribution of intragenic differentially methylated
      cytosines to X-linked gene expression, we examined DNA-protein interactions in a
      region in intron 3 of the human hypoxanthine phosphoribosyltransferase gene which
      contains at least one HpaII site methylated specifically on the active X. In
      vitro DNase I footprinting experiments using unmethylated DNA and HeLa nuclear
      extract identified three footprints (I-III). Footprints I and III flank an Alu
      repeat containing the HpaII site(s), one of which is contained within footprint
      II. Although methylation of the HpaII site had no effect on footprint II binding
      interactions, methylation of nearby CpGs substantially reduced the formation of
      three of the specific DNA-protein complexes binding to footprint II in mobility
      shift assays. Additionally, an A+T rich region immediately 5' to the HpaII
      containing Alu repeat was found to bind specifically to nuclear matrices in
      vitro. We suggest that differential methylation of CpGs may affect the binding of
      regulatory proteins in vivo, and that interactions between the footprint proteins
      and those binding to the matrix attachment region may be involved in controlling
      X-linked Hprt expression.

PMID- 7578243
TI  - Conserved sequence patterns in phages Mu and lambda DNA.
AB  - The genetic maps of bacteriophages Mu and lambda can be aligned with respect to
      the functions of their genes. We were interested to ascertain whether the
      congruence of gene order is reflected at the nucleotide sequence level. A sliding
      window analysis of sequences from the early regions of both phages revealed a
      substantial degree of similarity. Equally high scores, however, were found when
      the early region of Mu was compared to the late region of lambda and in self
      comparisons of either Mu or lambda. Hence, the similarity is due to a common
      pattern of nucleotides rather than to sequence similarities between functionally
      related genes. Employing degenerated scoring matrices we could show that
      primarily adenine and thymine residues contribute to the high scores and that a
      specific clustering of these residues is the basis for the conserved pattern.
      Since such a similarity was not observed with control sequences of other phages.
      Escherichia coli or eukaryotic viruses, the data support the notion that Mu and
      lambda have diverged from a common phage module. In general, our approach could
      offer a simple and sensitive way to trace distant relationships.

PMID- 7578244
TI  - A cDNA encoding the human type I hair keratin hHal.
AB  - A full-length cDNA of a human type I hair keratin was isolated that encodes a
      protein of 416 amino acids. Northern blot analysis shows that the mRNA is present
      in human scalp but not in hairless skin. Based on sequence homology comparisons
      with the four known mouse type I hair keratins mHal-4 the keratin could be
      identified as the human hair keratin hHal.

PMID- 7578246
TI  - Binding of RecA to anti-parallel poly(dA).2poly(dT) triple helix DNA.
AB  - Binding of RecA protein to conventional anti-parallel poly(dA).2poly(dT) triplex
      DNA has been studied using flow linear dichroism spectroscopy. The association
      requires the presence of cofactor analog adenosine 5'-O-3-thiotriphosphate (ATP
      gamma S) and occurs with a rate similar to that for the association of RecA to
      double-stranded poly(dA).poly(dT) DNA. The binding of RecA to DNA stiffens the
      nucleotide chain, as evidenced from high orientation already at low shear rates,
      and the complex with triplex DNA appears to be at least as stiff as that with the
      duplex DNA. Therefore, the observation of a lower magnitude of the LD spectrum at
      260 nm, in the triplex-RecA compared to the duplex-RecA complex, but retained
      magnitude of protein LD at 280 nm, indicates a markedly impaired orientation of
      nucleo-bases, possibly reflecting a perturbation by RecA on the third strand
      making its bases deviate strongly from perpendicularity. The circular dichroism
      spectrum, appearing immediately after dissociation of RecA by SDS, suggests an
      intact triplex structure, meaning that complexation with RecA has not dissociated
      the third strand. In conclusion, binding of RecA to triplex DNA does not modify
      the main organisation of the strands, but could affect the base-base interactions
      between them. Tilted bases could reflect a conformational change that RecA
      imposes also on the biological intermediate triplex structure to relax the base
      base hydrogen bonding between the DNA strands.

PMID- 7578245
TI  - Down-regulation of ornithine decarboxylase by an increased degradation of the
      enzyme during gastrulation of Xenopus laevis.
AB  - The present study was designed to analyze the regulation of the levels of the
      polyamines and their biosynthetic enzymes during embryonic development of Xenopus
      laevis. The activity of ornithine decarboxylase (ODC), a rate-controlling enzyme
      in polyamine biosynthesis, is elevated until, during gastrulation, there is a
      precipitous drop in activity. This is not attributable to a decrease in ODC mRNA
      content and polysome profiles reveal no apparent decrease in ODC message
      associated with polysomes. ODC synthesis seems to be maintained at a low,
      relatively constant rate until neurulation whereupon ribosome loading of ODC mRNA
      increases. During gastrulation the rate of ODC degradation increases
      dramatically, which can account for the decrease in ODC. S-Adenosylmethionine
      decarboxylase (AdoMetDC), another rate-controlling enzyme in polyamine
      biosynthesis, shows a low and constant activity from cleavage to neurulation.
      Subsequently, the AdoMetDC activity increases dramatically. The changes in
      AdoMetDC activity parallel the changes in AdoMetDC mRNA levels, suggesting a
      transcriptional control of AdoMetDC expression during this development period.
      The activities of ODC and AdoMetDC produce a steady increase in putrescine and
      spermidine content of the embryo. The spermine content also increases until
      gastrulation, but then decreases until the tailbud stage.

PMID- 7578247
TI  - Differences in DNA sequence recognition by the heat-shock factors of Drosophila
      melanogaster and the parasitic helminth Schistosoma mansoni.
AB  - It was recently shown that schistosome extracts contain heat-shock factor (HSF)
      activity that correlates with the pattern of hsp70 mRNA levels at different
      developmental stages of the parasite (Levy-Holtzman and Schechter (1994)
      Parasitology 108, 35-42). To extend our understanding of the HSF activity
      revealed in extracts of Schistosoma mansoni (Sm), it was further analyzed by
      competition experiments and compared with the well characterized HSF of
      Drosophila melanogaster (Dm). The interactions of HSF in Sm extracts (SmHSF) and
      HSF of Dm (DmHSF) with 32P-labeled heat shock element (HSE) probes, with and
      without unlabeled competitor DNA probes (HSE-related oligos), were analyzed by
      gel retardation assay. The binding and inhibition studies demonstrated that SmHSF
      and DmHSF differ in HSE sequence recognition: an array of three nGAAn inverted
      repeats according to the ideal consensus sequence (nGAAnnTTCnnGAAn) is recognized
      by DmHSF, but not by SmHSF. In the schistosome, binding is attained only when the
      third pentamer is a variant, composed of nGTAn instead of nGAAn. The presence of
      this variant in the promoter of the hsp70 gene of the parasite suggests
      coevolution of the variant sequence together with the SmHSF which interacts
      efficiently with the variant, but not with the ideal HSE sequence. Further
      inhibition studies revealed additional differences between SmHSF and DmHSF in
      recognition of the first and second nGAAn pentamers of HSE. In analogy to other
      systems of ligand-protein interactions, we propose that the complementarity
      between the HSE ligand and the HSF protein is higher in SmHSF, as compared to
      DmHSF.

PMID- 7578248
TI  - Bile salt-dependent lipase transcripts in human fetal tissues.
AB  - In human fetal pancreas, we identified two cDNA transcripts of the bile salt
      dependent lipase (BSDL) using reverse transcription followed by polymerase chain
      reaction (RT-PCR). The sequence of four overlapping segments obtained by RT-PCR
      matched the sequence of the 2.2 kb cDNA cloned from human adult pancreas (Reue et
      al. (1991) J. Lipid Res. 32, 267-276). A second RT-PCR product of approx. 1.1 kb
      was evidenced, the sequence of which corresponds to that of the BSDL-pseudogene
      transcript (Nilsson et al. (1993) Genomics, 17, 416-422). The short transcript is
      present in all tissues examined whereas the former one (2.2 kb) is either poorly
      (in liver and kidney) or not at all expressed in adult tissues, excepted in the
      pancreas. On the other hand, the 2.2 kb transcript specific of the BSDL gene was
      detected in all fetal tissues examined as early as the 6th week of gestation.
      Results also suggested that the fetal pancreas contains more 2.2 kb transcript
      than its adult counterpart. Therewith, BSDL was immuno-precipitated from fetal
      liver. The role of BSDL-gene expression during the fetal life is discussed.

PMID- 7578249
TI  - Cloning and sequence analysis of the TcP2 beta cDNA variants of Trypanosoma
      cruzi.
AB  - P2 beta acidic ribosomal protein is a relevant antigen in Chagas' disease. cDNA
      cloning demonstrated that Trypanosoma cruzi expresses at least six types of TcP2
      beta transcripts that differed by point nucleotides substitutions. The
      distribution and type of mutations seemed to follow the typical structural
      organization of eukaryotic acidic ribosomal proteins. Most of the synonymous
      changes clustered in the amino-terminus, suggesting that conservation of this
      domain was crucial for an equivalent functional ability of each TcP2 beta variant
      to bind to the ribosome. Interestingly, most amino acid changes in the central
      globular and hinge domains caused polymorphism in putative phosphorylatable
      sites.

PMID- 7578250
TI  - Cloning a cDNA from human NK/T cells which codes for a protein with high proline
      content.
AB  - A cDNA clone, B4-2, was isolated from a natural killer (NK) minus T cell
      subtractive library. The B4-2 clone coded for an mRNA of 2061 bp in length. It
      encodes a deduced 327 aa protein with a calculated molecular mass of 35.2 kDa.
      Searching of B4-2 DNA and protein sequences against various databases revealed no
      high homology to other sequences. However, B4-2 has an unusually high proline
      content (13%), contains a putative nuclear targeting sequence, and has several
      SPXX motifs which are frequently found in gene regulatory proteins. One of the
      stretches of prolines in B4-2 closely resembles the ligand for proteins with SH3
      domains. Northern hybridization data showed that B4-2 is not a lymphoid specific
      gene and is expressed in a hepatoma cell line and also weakly transcribed or
      absent in a variety of other cells. A polyclonal antiserum raised against
      recombinant B4-2 recognizes a 32-34 kDa protein in lymphocytes.

PMID- 7578251
TI  - Molecular cloning of cDNAs encoding precursors of frog skin antimicrobial
      peptides from Rana rugosa.
AB  - Gaegurins, a family of peptide antibiotics with sizes ranging from 24 to 37 amino
      acids, have recently been purified from Rana rugosa skin (Park, J.M., Jung, J.-E.
      and Lee, B.J. (1994) Biochem. Biophys. Res. Commun. 205, 948-954). Two complete
      cDNAs encoding gaegurins 4 and 5 were isolated from a library constructed with
      the frog skin mRNAs. Each clone contained a single open reading frame that
      encodes a gaegurin precursor polypeptide. The deduced amino acid sequences
      revealed that the precursors have a unique tripartite structure: a putative
      signal sequence at the NH2-terminus followed by an acidic spacer region rich in
      glutamic and aspartic acids, and a mature gaegurin peptide at the COOH-terminus.
      Similar modes of organization were also found in antimicrobial or opioid peptide
      precursors of other frog species, although their mature peptides show little
      sequence homology. The family of peptides with this characteristic now expands.
      Northern analysis revealed that gaegurins are extensively expressed in the skin
      tissue, but not in liver and muscle.

PMID- 7578252
TI  - Molecular cloning of 25-hydroxyvitamin D-3 24-hydroxylase (Cyp-24) from mouse
      kidney: its inducibility by vitamin D-3.
AB  - A cDNA encoding a 25-hydroxyvitamin D-3 24-hydroxylase, Cyp-24, has been isolated
      from mouse kidney cDNA library by hybridization screening. Mouse Cyp-24, coding
      for 514 amino acid residues, shared 82.1 and 94.7% amino acid identity with human
      and rat CYP24s, respectively. Among mouse organs examined, Cyp-24 mRNA could be
      detected in the kidney. When mice were treated with vitamin D-3, Cyp-24 mRNA was
      induced in the kidney.

PMID- 7578253
TI  - Possible involvement of a ubiquitous and several distinct elements in the
      transcription regulation of the chicken H3 histone gene family.
AB  - We have studied possible modes of transcription regulation of four members (H3
      II, H3-III, H3-IV and H3-V) of the twelve chicken H3 genes. Results of transient
      CAT assays using 5'-truncated mutants of H3-IV, together with those reported
      previously for H3-II and H3-III, indicated that all these four H3 genes possessed
      a ubiquitous element, the CCAAT sequence, in addition to several distinct
      elements. Transient CAT assays using the 5'-extended mutants of these four H3
      genes showed that the promoter activities decreased with increasing lengths of
      the 5'-extended fragments, and that the effects were strong for H3-IV and H3-V,
      but only moderate for H3-II and H3-III.

PMID- 7578254
TI  - Analysis of cis-acting regions upstream of the rat Na+/K(+)-ATPase alpha 1
      subunit gene by in vivo footprinting.
AB  - By means of in vivo footprinting, we examined the putative cis-acting DNA
      elements located between -50 and -122 of rat Na+/K(+)-ATPase alpha 1 subunit gene
      ATP1A1. Proximal and distal GC box sequences and a consensus sequence for the
      active transcription factor (ATF) were protected for all the tissues examined
      (kidney, brain and liver). Putative cooperation between two binding factors on
      the ATF site and the proximal GC box was observed. The overall in vivo
      footprinting profiles of the three tissues did not exhibit any marked differences
      that could account for the variation in the extent of tissue-specific
      transcription. The alpha 1 regulatory element (ARE) found by Suzuki-Yagawa et al.
      does not appear to be an element responsible for tissue-specific regulation of
      the gene.

PMID- 7578255
TI  - Identification of a recognition element for CAAT-enhancer binding proteins
      (C/EBPs) in the elastin promoter.
AB  - DNase I footprinting experiments with a DNA fragment of the human elastin
      promoter have revealed a protected segment comprised between -156 and -172
      nucleotides from the translation start site. Various types of gel retardation
      experiments indicate that the protected element binds different members of the
      C/EBP family of transcription factors. CAT (chloramphenicol acetyltransferase)
      fusion constructs carrying the wild type or a mutated promoter sequence were
      transfected into NIH3T3 and chick embryo aorta cells. The mutation significantly
      lowered CAT expression in NIH3T3 cells, but was ineffective in aorta cells.
      Cotransfection of the CAT promoter constructs with eucaryotic vectors expressing
      C/EBPs, did not affect the production of the reporter gene in NIH3T3 cells; on
      the contrary a several-fold increase of CAT activity was observed in aortic
      cells. This increase, however, was identical for the wild type and the mutated
      constructs. Taken together the data indicate that the elastin promoter contains a
      recognition site for proteins of the C/EBP family and that the function of this
      cis-acting element on basal elastin transcription varies with the cell type.

PMID- 7578256
TI  - Molecular cloning of two types of cDNA encoding subunit RC6-I of rat proteasomes.
AB  - A new subunit, named RC6-I, of the rat 20 S proteasome was purified and the
      partial amino acid sequences of several peptide fragments obtained by digestion
      with lysyl-endopeptidase were determined by Edman degradation. Amplification of
      cDNAs encoding RC6-I by the polymerase chain reaction (PCR) technique revealed
      two types of cDNA, tentatively designated as RC6-IL and RC6-IS in order of size.
      The nucleotide sequences of the two cDNAs are identical except that RC6-IL
      contains an insertion of 18 nucleotides in the coding region compared with RC6
      IS. The polypeptide predicted from the open reading frame of RC6-IS cDNA consists
      of 248 amino acid residues with a calculated molecular weight of 27,783. These
      values are consistent with those obtained by protein chemical analyses. Computer
      assisted homology analysis showed that RC6-I belongs to the alpha-type subfamily
      of the proteasome gene family, which shows similarity to the alpha-subunit of the
      archaebacterium Thermoplasma acidophilum proteasome, and that the 18 nucleotide
      insert, encoding six amino acid residues, VVASVS, appears to be unique to RC6-IL,
      because this motif has not been conserved in any other alpha-type subunit. By
      reverse transcription (RT)-PCR analysis, the mRNAs for both RC6-IL and RC6-IS
      were found in all the rat tissues examined. These results suggest that
      proteasomes are present as a heterogeneous population, possibly for acquisition
      of diversity of functions.

PMID- 7578257
TI  - Structure and evolution of Paramecium hemoglobin genes.
AB  - Hemoglobin (Hb) genes have been cloned from three different species of ciliated
      protists, P. multimicronucleatum, P. triaurelia and P. jenningsi. Southern
      blotting of the genomic DNAs using the P. caudatum Hb cDNA showed both
      intraspecies variation in different stocks of P. caudatum and interspecies
      variation within the genus Paramecium. The isolated Hb genes were composed of
      118, 117 and 117 codons, and interrupted by a short intron with 27, 29 and 29 bp
      at the same position, in P. multimicronucleatum, P. triaurelia and P. jenningsi,
      respectively. This suggests that the one-intron and two-exon structure has been
      conserved in the Hb genes in this genus. The amino acid sequences of the
      Paramecium Hbs were more than 87% identical to one another and homologous to
      those from the other ciliated protists Tetrahymena thermophila and T. pyriformis,
      the green alga Chlamydomonas eugametos, and the cyanobacterium Nostoc commune
      Hbs, all of which consist of about 120 amino acid residues (120-aa group). In
      particular, the amino acid sequences of the P. triaurelia and P. jenningsi Hbs
      were the same, although there were 20 nucleotide differences between the coding
      regions in the two genes. A maximum likelihood inference as to the phylogenetic
      relationships among these genes suggests that the Paramecium Hbs genes have
      evolved more rapidly than the other genes in the 120-aa group, and that P.
      triaurelia and P. genningsi are sibling species and the P. aurelia complex became
      a small cell after it separated from P. jenningsi.

PMID- 7578258
TI  - Detection, simultaneous display and direct sequencing of multiple nuclear hormone
      receptor genes using bilaterally targeted RNA fingerprinting.
AB  - We have developed a PCR-based method to detect, display and directly sequence
      multiple members of the nuclear hormone receptor (NHR) gene family. Our approach
      employs the basic concepts of RNA fingerprinting (Welsh et al. (1992) Nucleic
      Acids Res. 20, 4965-4970; Stone, B. and Wharton, W. (1994) Nucleic Acids Res. 22,
      2612-2618) and differential display PCR (Liang, P. and Pardee, A.B. (1992)
      Science 257, 967-971), with modifications. In contrast to the previous methods,
      two conserved regions within the gene family were targeted to derive primers for
      PCR amplification. One of the conserved sites was used to deduce primers for cDNA
      synthesis. We believe that this strategy led to increased specificity. The use of
      degenerate primers with low redundancy in both reverse transcription and PCR
      steps also contributed to enhanced signal-to-noise ratio. The ability to directly
      sequence the amplified fragments constitutes a vast improvement over the previous
      methods. This method permitted the successful identification and simultaneous
      display of six different NHR genes, which included the previously unreported rat
      homolog of COUP-TFI and a recently described orphan receptor. We believe that
      this approach provides a convenient and rapid screening method for detecting and
      characterizing members of a gene family.

PMID- 7578259
TI  - Cloning and expression of a myc family member from the pituitary gland of the
      Rainbow trout, Oncorhynchus mykiss.
AB  - A myc gene cloned from a Rainbow trout pituitary gland cDNA library is described.
      This clone (Tmyc2) shows extensive homology to Rainbow trout C-myc, which is
      expressed in the liver. Tmyc2 does not appear in the liver but is expressed in
      the pituitary gland (1.9 kb transcript), brain (2.0 kb transcript) and, at very
      low levels, in the heart (2.0 kb transcript). Tmyc2 contains three highly
      modified areas within the coding sequence, one of which shows an extensive loss
      of acidic residues that is uncommon in C-myc family members and may be important
      in determining the function of Tmyc2 in the pituitary gland and brain.

PMID- 7578260
TI  - Hypoxia induces AP-1-regulated genes and AP-1 transcription factor binding in
      human endothelial and other cell types.
AB  - Hypoxia results in differential expression of specific genes in certain cell
      types. In endothelial cells, hypoxia activates several genes that are known to be
      inducible by transcription factor AP-1, including endothelin-1 and platelet
      derived growth factor-B (PDGF-B). In this study we demonstrated that other AP-1
      inducible genes are activated by hypoxia in these cells, including collagenase IV
      and c-jun, and sought to correlate the activation of genes by hypoxia with the
      activation of transcription factor AP-1. Depending upon the type of cell studied,
      hypoxic exposure resulted in the induction of AP-1 transcription factor DNA
      binding activity with wide variations in levels of binding. The magnitude of
      activation of transcription factor AP-1 by hypoxia did not always strictly
      correlate with the level of induction of AP-1-inducible genes. This finding
      indicates a requirement for additional mechanisms of controlling transcription
      beyond the simple activation of AP-1 factor DNA-binding activity for the
      activation of AP-1-inducible genes during hypoxia. Hypoxia has been reported to
      lower the intracellular redox potential. The effect of redox state changes on AP
      1 transcription factor activity and on the activation of AP-1-inducible genes was
      also studied. PDTC, a potent reducing agent, activated the AP-1 transcription
      factor in HeLa cells, and also resulted in increased accumulation of c-jun mRNA
      in these cells. In contrast to PDTC-mediated activation of the AP-1 transcription
      factor and the subsequent induction of the AP-1-regulated c-jun gene, hypoxic
      activation of AP-1 transcription factor binding to its cognate DNA sequence did
      not activate the c-jun gene in HeLa cells, thus documenting distinct differences
      in signals generated by the reducing intracellular microenvironments created by
      hypoxia and PDTC. These results demonstrate the induction of AP-1 transcription
      factor activity by hypoxic environments, but suggest that additional factors or
      cell-specific signals are involved in the regulation of hypoxia-induced genes.

PMID- 7578261
TI  - Expression of genes encoding peroxisomal proteins in Saccharomyces cerevisiae is
      regulated by different circuits of transcriptional control.
AB  - In Saccharomyces cerevisiae induction of the FOX3 gene, encoding peroxisomal 3
      oxoacyl-CoA thiolase, by growth on oleate as sole carbon source, is exerted via
      the cis-acting DNA element designated oleate response element (ORE) (Einerhand et
      al. (1991) Eur. J. Biochem. 200, 113-122). The transcription factor(s) binding to
      this upstream activation site (UAS) are still unknown, however. Induction of
      another peroxisomal enzyme, citrate synthase (CIT2) is dependent on the products
      of two genes called RTG1 and RTG2 (Liao and Butow (1993) Cell 72, 61-71). In the
      present study we have investigated whether RTG1 controls other genes coding for
      peroxisomal proteins, and whether such control takes place via the ORE. A number
      of genes coding for a variety of peroxisomal proteins such as: thiolase and
      catalase (peroxisomal matrix proteins), PAS3p (a peroxisomal membrane protein)
      and PAS10p (a protein involved in the import of peroxisomal proteins) were
      studied in their response to RTG1. Although the RTG1 and 2 products proved to be
      required for the increase in number and volume of peroxisomes upon induction by
      oleate, the single promoter output of the chosen set of genes remained
      practically unchanged in a rtg1 mutant strain. In addition gel retardation
      experiments indicated that RTG1 does not bind to the ORE. The behavior of genes
      coding for the various proteins also varied during repression, derepression and
      induction, indicating that probably a number of proteins are involved in tuning
      the output of each gene to cellular demand.

PMID- 7578262
TI  - Mutations of Arabidopsis thaliana pre-tRNA(Tyr) affecting pseudouridylation of
      U35.
AB  - The structural and sequence requirements for the biosynthesis of tRNA(Tyr)
      pseudouridine (psi 35) have been studied. Nucleotide substitution at the 32nd
      position slightly reduced modification efficiency in the case of transition (C32
      to U32) while transversion (C32 to G32) had no effect on the modification process
      in wheat germ extract. Insertion of one nucleotide into the anticodon stem caused
      a 2-fold reduction of modification efficiency. Mutants with a partially deleted
      12 nt long intron of pre-tRNA(Tyr) exhibited different effects: deletion of 5 nt
      (7 nt long intron) gave only a reduction in pseudouridylation while deletion of 7
      nt (5 nt long intron) almost completely abolished the reaction. The generated
      mini-substrate consisting of pre-tRNA(Tyr) anticodon stem and intron sequence was
      partially modified which proved that the crucial elements for recognition of psi
      35 introduction had to present in this construct.

PMID- 7578263
TI  - Rat lysyl hydroxylase: molecular cloning, mRNA distribution and expression in a
      baculovirus system.
AB  - A cDNA library from rat lung was screened with a chicken lysyl hydroxylase cDNA,
      and several overlapping rat lysyl hydroxylase cDNAs were isolated. The complete
      cDNA was 91 and 77% identical, respectively, to the human and chicken lysyl
      hydroxylase cDNAs at the protein level. By Northern blot, the rat lysyl
      hydroxylase cDNA recognized a single 3.2 kb mRNA that was present in a wide
      variety of rat tissues. In order to further confirm the identity of this cDNA,
      the cDNA was expressed in insect cells via a baculovirus vector. These cells
      produced an 85 kDa protein with lysyl hydroxylase activity. The recombinant lysyl
      hydroxylase had a specific activity and Km values for its substrates that were
      similar to those of the enzyme isolated from chick embryos. The fact that this
      single lysyl hydroxylase cDNA encodes a protein sufficient for lysyl hydroxylase
      activity is consistent with previous biochemical findings that lysyl hydroxylase
      only requires a single type of subunit for its activity.

PMID- 7578264
TI  - Cloning and structural analysis of the gene for cAMP-dependent protein kinase
      catalytic subunit from Plasmodium yoelii.
AB  - We isolated the gene encoding the cAMP-dependent protein kinase catalytic subunit
      (cAPK[C]) from Plasmodium yoelii by screening a genomic library for the DNA
      fragment as produced by the polymerase chain reaction. The deduced protein of 341
      amino acids conserves residues that are important for the function of
      serine/threonine protein kinases and shows the highest homology to cAPK[C]s of
      other organisms. However, P. yoelii cAPK[C] has 8 residues, which are perfectly
      conserved in cAPK[C]s of other organisms, radically replaced with residues having
      different side-chain properties. It is stressed that two radical replacements
      occur in regions for the binding with a regulatory subunit and/or a heat-stable
      inhibitor protein.

PMID- 7578265
TI  - Purification and characterization of an endothelial cell-viability maintaining
      factor from fetal bovine serum.
AB  - Serum is an essential requirement for the growth and long-term survival of human
      endothelial cells, even in the presence of such defined elements such as
      polypeptide growth factors and hormones. A polypeptide from fetal bovine serum
      was isolated and characterized on the basis of long-term survival of human
      endothelial cells in serum-free culture. The endothelial cell viability
      maintaining factor has been purified to homogeneity by a combination of
      polyethylene glycol precipitation, hydroxylapatite, gel permeation and reverse
      phase high performance liquid chromatography. The final purified endothelial cell
      viability maintaining factor has a molecular weight of 65,000 (reduced) and has
      been identified as bovine apolipoprotein H by amino-terminal amino acid sequence
      analysis and Western blot analysis. Endothelial cell viability maintaining factor
      improved a long-term viability of human endothelial cells at maximal
      concentrations of 2.5-5 micrograms protein/ml in serum-free medium.

PMID- 7578266
TI  - The influence of antioxidants and cycloheximide on the level of nitric oxide in
      the livers of mice in vivo.
AB  - When injected into mice prior to the NO generation increase induced with
      lipopolysaccharide (LPS) from Escherichia coli, exogenous antioxidants
      diethyldithiocarbamate (DETC) or phenazan (sodium 3.5-di-tert-butyl-4
      oxiphenylpropionate) as well as the inhibitor of protein biosynthesis,
      cycloheximide (CHI) attenuated the NO production in mouse liver in vivo. These
      data demonstrated the key role of free radicals, which were likely, active oxygen
      species, in the synthesis of inducible NO-synthase (iNOS) responsible for the NO
      production in this organ. Similar effects of phenazan and CHI were observed in
      livers of mice treated with gamma-irradiation or LPS + Fe(2+)-citrate, which
      suggested that these treatments also induced 1NOS synthesis through initiating
      the action of active oxygen species. The rate of NO synthesis was estimated by
      accumulation of paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC)
      detected using the EPR method. The formation of MNIC-DETC complexes was found in
      the brain of mice pre-treated with LPS + Fe(2+)-citrate which seemed to be due to
      iNOS synthesis stimulated by this treatment.

PMID- 7578267
TI  - Cooperative effects of interferon-gamma on the induction of NADPH oxidase by
      retinoic acid or 1,25(OH)2-vitamin D3 in monocytic U937 cells.
AB  - The effect of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25-D3) or human
      recombinant interferon-gamma (IFN-gamma) on the induction of NADPH oxidase was
      studied in premonocytic U937 cells. Differentiation with the combination of
      either RA (1 microM) or 1,25-D3 (10 nM) with IFN-gamma (100 IU/ml) induced NADPH
      oxidase activity as demonstrated by increased superoxide anion (O2-) generation
      in response to stimulation with phorbol myristate acetate (PMA, 100 nM).
      Induction of NADPH oxidase activity was preceded by increases in mRNA levels of
      p47-phox, p67-phox and gp91-phox, which encode three subunits of the enzyme, and
      immunoblot analysis of the p47-phox and p67-phox proteins revealed that the
      increases in mRNA levels were equally reflected by increases in protein levels.
      In contrast, RA, 1,25-D3 or IFN-gamma alone did not induce NADPH oxidase activity
      which correlated with their failure to increase p67-phox and gp91-phox mRNA
      levels. The mRNA of p21 rac1, a GTP-binding protein that regulates NADPH oxidase
      activity in macrophages, was constitutively expressed in undifferentiated cells
      and was not affected by differentiation. These data indicate that induction of a
      functional NADPH oxidase in premonocytic U937 cells requires the cooperative
      actions of IFN-gamma plus RA or 1,25-D3 and is reflected in the increased
      expression of p67-phox and gp91-phox.

PMID- 7578268
TI  - Lymphoma cells selected for resistance against the cytotoxic effect of oxygenated
      sterols are also resistant to nonsteroidal antiestrogens.
AB  - Oxygenated derivatives of cholesterol and related compounds (oxysterols) have
      long been known to be cytotoxic to many different cell types. The mechanism of
      this cytotoxic effect is not fully understood. Our laboratory has earlier
      reported that oxysterol cytotoxicity resembles that of nonsteroidal antiestrogens
      in some aspects: (i) the cytotoxic action of both types of compounds is blocked
      by inhibitors of protein or RNA synthesis, and (ii) both classes of compounds
      bind with high affinity to the microsomal antiestrogen binding site, a protein
      which may mediate the cytotoxicity of its ligands. We have now extended these
      studies by developing cell lines which are resistant to the cytotoxic action of
      oxysterols. Oxysterol-resistant cells were isolated by exposing two murine
      lymphoma cell lines, K36 and EL4, to incremental concentrations of 7
      ketocholestanol. Intriguingly, the resistant cells thus obtained also exhibited
      considerable resistance to the cytotoxic effects of nonsteroidal antiestrogens
      such as tamoxifen and clomiphene, having LD50 values which were 10-100-times
      higher than that of the parental cells. The resistance appeared to be selective
      for oxysterols and antiestrogens and did not extend to non-specific toxic agents
      such as azide, ethanol, Triton-X100, or heat. The biochemical basis of the
      resistance is not clear but is not due to diminished cellular uptake or increased
      metabolism of the cytotoxic agents or to changes in the antiestrogen binding
      protein. The availability of the resistant cell lines should facilitate further
      studies on the mechanism of oxysterol- and antiestrogen-induced cell death.

PMID- 7578270
TI  - Mitogenic stimulation of human lymphocytes mediated by a cell surface elastase.
AB  - A ca. 45-kDa protein which was recently identified and purified to homogeneity
      from a solid tumor cell line as a T-cell mitogen was found to have significant
      sequence similarities with human monocyte/neutrophil elastase inhibitor (EI) [1].
      Since EI is a known substrate for elastase, a determination of whether a cell
      surface expressed elastase-like molecule might be the binding protein for this 45
      kDa factor and mediate mitogenic signal transduction was undertaken. First, the
      surface of tumor infiltrating lymphocytes, TIL 660, the indicator cell line used
      for the purification of this mitogen, was shown to stain positively with an anti
      elastase antibody using flow cytofluorometry for quantitation. Then, after
      observing an inverse correlation between cell surface staining and the
      proliferative status of the TILs, behavior which might be expected of a growth
      factor receptor upon activation, mitogenic signal transduction was attempted
      through the elastase-like molecules of the lymphocytes' plasma membrane with the
      anti-elastase antibody in the role of mitogen. A greater than 4-fold mitogenic
      stimulation was observed when this antibody was covalently linked to latex beads;
      in contrast, addition of the soluble form of the same antibody did not result in
      any increase in [3H]thymidine incorporation into the cells' DNA. Hence, these
      data support induced clustering of an elastase-like molecule on the lymphocyte
      surface as a mediator of mitogenesis and suggest that the binding protein for
      mitogenic signal transduction induced by the 45-kDa protein, a member of the
      serine protease inhibitor (serpin) superfamily of proteins, is a molecule with
      structure similar to a serine protease.

PMID- 7578269
TI  - A serpin from human tumor cells with direct lymphoid immunomodulatory activity:
      mitogenic stimulation of human tumor-infiltrating lymphocytes.
AB  - A serum-free supernatant from an epidermal carcinoma cell line has previously
      been shown to contain mitogenic activity for human tumor infiltrating lymphocytes
      in culture [1]. From this conditioned medium we have now purified to homogeneity,
      as determined by SDS-PAGE analysis, a ca. 45 kDa protein which stimulates
      [3H]thymidine incorporation into the DNA of these human T-lymphocytes. Amino acid
      composition data and immunoreactivity of the purified protein as well as sequence
      analyses of 7 tryptic fragments obtained therefrom suggest a strong similarity
      with human monocyte/neutrophil elastase inhibitor, which is a member of the
      serine protease inhibitor (serpin) superfamily. We have previously identified and
      purified from the same conditioned medium a 36 kDa protein with myeloid
      immunomodulatory activity [2]. Taken together, these two reports support the role
      of tumor-derived soluble factors in tumor immunosurveillance.

PMID- 7578271
TI  - Src-transformation of mouse fibroblasts induces a Ca(2+)-activated K+, current
      without changing the T-type Ca2+ current.
AB  - Membrane currents of src-transformed NIH3T3 mouse fibroblasts were analyzed in
      comparison with their non-transformed counterparts using the patch-clamp
      technique. Normal NIH3T3 cells exhibit two types of Ca2+ currents and a membrane
      current of ohmic behaviour (current amplitude 135 pA at +30 mV) that can
      partially be blocked by Cd2+. Src-transformed NIH3T3 cells show an additional
      membrane current that becomes activated after the establishment of the whole-cell
      configuration with a maximum amplitude of 1040 pA at +30 mV within 30-60 s. This
      current then inactivates irreversibly within 5-10 min. The additional current is
      highly K(+)-selective and Ca(2+)-dependent but voltage-independent. It can be
      blocked by charybdotoxin (IC50 = 20 nM) and by internal tetraethylammonium (TEA;
      IC50 = 2.9 mM), but it is not sensitive to external TEA (up to 30 mM). Single
      channel analysis revealed only one K+ channel type with a conductance of 37 pS at
      negative potentials and 18 pS at positive potentials (in symmetrical 145 mM K+
      solutions), a voltage-independent open-state probability of 0.6 and the same
      pharmacological properties as the macroscopic KCa current. The properties of the
      KCa current and the underlying channels of src-transformed NIH3T3 cells are
      identical to those observed in ras-transformed NIH3T3 cells. In contrast, src- or
      ras-transformation affects differently the voltage-dependent, transient (T-type)
      Ca2+ current. While ras-transformation of NIH3T3 cells suppresses their T-type
      Ca2+ current, this current remains unchanged in src-transformed NIH3T3 cells.

PMID- 7578272
TI  - Metabolism of homocysteine, its relation to the other cellular thiols and its
      mechanism of cell damage in a cell culture line (human histiocytic cell line U
      937).
AB  - This study shows that the intracellular concentration of homocysteine in cultured
      cells is kept low due to an accumulation in the medium. The intracellular level
      of homocysteine was decreased when its precursor, methionine, was omitted from
      the culture medium. Intracellular glutathione and cysteine were lowered in
      cystine-deficient medium. Intracellular glutathione was also lowered when copper
      ions were added to the culture medium. It is evident from this study that the
      intracellular concentration of homocysteine was not influenced by the lowered
      level of glutathione and/or cysteine. High amounts of homocysteine added to the
      medium give rise to an increase of intracellular reduced homocysteine, which
      participates in the transsulfuration pathway and can replace cysteine in the
      synthesis of glutathione. The addition of relatively high amounts of reduced
      homocysteine (500 mumol/l) in the presence of copper ions (100 mumol/l) to the
      culture medium can be directly toxic to the cells, possibly due to oxygen
      radicals formed by thiol auto-oxidation. Whilst the level of homocysteine in this
      study using short-time cell culture experiment is much higher than the mild
      hyperhomocysteinemia thought to be atherogenic in humans, it is conceivable that
      over a longer time course these levels of homocysteine could be sufficient to
      induce endothelial dysfunction, eventually leading to atherosclerosis.

PMID- 7578273
TI  - Bacillus amyloliquefaciens possesses a second type I signal peptidase with
      extensive sequence similarity to other Bacillus SPases.
AB  - A second sipS2(BA) gene was PCR cloned from Bacillus amyloliquefaciens. The
      deduced aa sequence is similar to those of the SPases of B. subtilis, B.
      amyloliquefaciens, and B. licheniformis and the domain structure of the gene has
      been preserved. A low level of monocistronic gene transcription could be shown
      using Northern analysis. The sipS2(BA) gene was mapped to a region downstream of
      an E. coli fruA gene homologue and shown to express a 21 kDa protein in
      Escherichia coli.

PMID- 7578275
TI  - Gangliosides enhance IgE receptor-dependent histamine and LTC4 release from human
      mast cells.
AB  - Releasability of mast cells and basophils to an IgE-dependent stimulus is
      regulated by extra- and intracellular factors which are only partly understood.
      As gangliosides are known to modulate receptor-dependent processes in various
      cell types, we have evaluated the effect of these molecules on mast cell mediator
      release. Human skin mast cells and the human mast cell line HMC1 were pretreated
      with the gangliosides GM2, GM3 and GD1a as well as with asialo-GM3, heparin and
      buffer alone (controls). After washing, the cells were stimulated with anti-IgE,
      calcium ionophore A 23187, N-FMLP or substance P. All gangliosides but not asialo
      GM3 and heparin augmented anti-IgE-induced mediator release in a dose-dependent
      fashion, whereas the release to A 23187, N-FMLP and substance P remained
      unaffected. Only sequential but not simultaneous addition of ganglioside and anti
      IgE showed an enhancement in mediator release compared to controls. Mediator
      release in both ganglioside-pretreated cells and controls was calcium-dependent
      and could be inhibited by pretreatment of cells with staurosporine or dibutyryl
      cAMP, indicating an unchanged signal transduction. Gangliosides appear to
      specifically optimize IgE-receptor-ligand interaction and alterations in cellular
      gangliosides could thus induce enhanced releasability as observed in atopics.

PMID- 7578274
TI  - The protein kinase from mitotic human cells that phosphorylates Ser-209 on the
      casein kinase II beta-subunit is p34cdc2.
AB  - Casein kinase II is a highly conserved enzyme that is essential for viability. In
      cells, the casein kinase II beta-subunit is phosphorylated at an
      autophosphorylation site and at a site (Ser-209) that is maximally phosphorylated
      in mitotic cells. To identify protein kinase activities that phosphorylate Ser
      209, we fractionated extracts from mitosis-arrested human Burkitt lymphoma MANCA
      cells. A single Ser-209 kinase activity was detected following each fractionation
      step. The Ser-209 kinase was purified to a specific activity of approx. 250
      nmol/min per mg and efficiently phosphorylated histone H1, a synthetic peptide
      containing Ser-209 (Ser-209 peptide), myelin basic protein and casein. Immunoblot
      analysis demonstrated that all fractions containing Ser-209 kinase activity
      contained p34cdc2. Furthermore, depletion of the Ser-209 kinase activity with
      p13suc1-Sepharose and anti-p34cdc2 antiserum demonstrated conclusively that the
      isolated Ser-209 kinase is p34cdc2. These studies provide strong biochemical
      evidence that p34cdc2 is the enzyme that phosphorylates Ser-209 on the beta
      subunit of CKII in mitotic cells. In addition, these results indicate that the
      Ser-209 peptide can be utilized as a specific reagent for the assay of p34cdc2
      activity in mitotic extracts, since no other Ser-209 peptide kinase activities
      were detected.

PMID- 7578276
TI  - Oversulfated fucoidan and heparin suppress endotoxin induction of plasminogen
      activator inhibitor-1 in cultured human endothelial cells: their possible
      mechanism of action.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a primary endogenous inhibitor of
      tissue-type plasminogen activator (t-PA). In this study, we examined the effects
      of oversulfated fucoidan (OSF) derivatives and heparin on lipopolysaccharide
      (LPS)-induced release of PAI-1 antigen from cultured human umbilical vein
      endothelial cells (HUVEC). Addition of LPS (10 micrograms/ml) enhanced the
      release of PAI-1 by HUVEC but not of t-PA antigen. At 18 h, a 2.4-fold increase
      in the extracellular PAI-1 level was observed. The increased PAI-1 level was
      reduced to control level by the simultaneous addition of 10 micrograms/ml of OSF
      or heparin. The suppressive effect of native fucoidan was negligible. We also
      examined the molecular size effect of OSF, using 10-20, 20-40, and 40-60 kDa
      fragments. The result indicated that these fragments were effective as well as
      the 100-130 kDa form of OSF, hence suggesting an important role of the degree of
      sulfation. Interleukin-1 beta (IL-1 beta) is a potent inducer of PAI-1 in
      cultured HUVEC. Heparin, OSF, and its fragments did not suppress the IL-1 beta
      induced release of PAI-1 antigen. Treatment of HUVEC with heparitinase or
      monoclonal antibody against heparin sulfate proteoglycan (HSPG) resulted in a
      complete loss of its ability to enhance PAI-1 release in response to LPS
      stimulation, while the chondroitinase ABC treatment hardly affected the PAI-1
      production. These results suggest that HSPG is involved in the initial binding of
      LPS to HUVEC. The suppressive effects of OSF and heparin on LPS-induced PAI-1
      release may result from the inhibition of LPS binding to the cell surface HSPG.

PMID- 7578277
TI  - Modulation by 1,25(OH)2-vitamin D3 of the adenylyl cyclase/cyclic AMP pathway in
      rat and chick myoblasts.
AB  - We have previously reported that the calciotropic hormone 1,25(OH)2-vitamin D3
      stimulates influx of Ca2+ into cultured rat and embryonic chick myoblasts via
      voltage sensitive Ca(2+)-channels. In the present study, we show that this effect
      of 1,25(OH)2D3 requires the mediation of the adenylylcyclase signalling system
      since the hormone-dependent Ca2+ influx is abolished by specific inhibitors of
      adenylylcyclase and protein kinase A and mimicked by forskolin and dibutyryl
      cAMP. 1,25(OH)2D3-stimulated elevations in cellular cAMP paralleled increases in
      Ca2+ uptake, further suggesting a coupling of adenylylcyclase activation and
      calcium influx. Fluoride and GTP gamma S mimicked 1,25(OH)2D3-stimulation of
      calcium influx while GDP beta S suppressed the effect of the hormone. Cholera
      toxin and Bordetella pertussis toxin both increased 45Ca2+ uptake in rat and
      chick myoblasts. The hormone further increased cholera toxin actions, but was
      unable to modify pertussis toxin-induced 45Ca2+ uptake, suggesting a similar
      target of action for pertussis toxin and 1,25(OH)2D3. Incubation of microsomal
      membranes with the sterol (10 nM, 2 min) markedly displaces (-32%) [35S]GTP gamma
      S binding to the membranes. ADP-ribosylation of the pertussis toxin-sensitive 41
      kDa substrate was significantly increased (+40%) in 1,25(OH)2D3-pretreated cells.
      These results suggest that 1,25(OH)2D3-stimulated influx of Ca2+ into rat and
      embryonic chick cultured myoblasts sequentially requires inhibition of a
      pertussis toxin-sensitive G protein, accumulation of cAMP and activation of
      dihydropyridine-sensitive Ca(2+)-channels through PKA-mediated phosphorylation
      events.

PMID- 7578279
TI  - Kraepelin's legacy: paradigm or pitfall for modern psychiatry?

PMID- 7578278
TI  - Hydrogen peroxide-and fetal bovine serum-induced DNA synthesis in vascular smooth
      muscle cells: positive and negative regulation by protein kinase C isoforms.
AB  - Hydrogen peroxide and fetal bovine serum stimulate DNA synthesis in growth
      arrested smooth muscle cells with remarkably similar kinetics and cell density
      dependence. However, while stimulation with fetal bovine serum results in cell
      proliferation, that by H2O2 is followed by cell death. Depletion of conventional
      and novel protein kinase C isoforms, resulting from a long treatment with phorbol
      12-myristate-13-acetate, further increases H2O2-induced DNA synthesis. On the
      other hand, the specific protein kinase C inhibitor calphostin C abolished the
      increased DNA synthesis promoted by fetal bovine serum or H2O2. H2O2 increases
      protein kinase C activity in smooth muscle cells. This effect is markedly
      reduced, but not abolished, by down-regulation of the alpha, delta and epsilon
      protein kinase C isoforms. Thus, the zeta isoform of protein kinase C, which is
      not down-regulated, may be responsible for the residual H2O2 stimulation of
      protein kinase C. In conclusion, the results obtained show that H2O2 stimulates
      protein kinase C activity and DNA synthesis in growth-arrested smooth muscle
      cells: these events are not followed by cell proliferation but rather by cell
      death. This H2O2 stimulated DNA synthesis appears to be negatively controlled by
      alpha, delta and epsilon isoforms and positively controlled by the zeta isoform
      of protein kinase C.

PMID- 7578280
TI  - Kraepelin and modern psychiatry.
AB  - A summarised account is given of Emil Kraepelin's research in the field of mental
      disorder, underlining his emphasis on objectivity and natural science and the
      need for a multi-disciplinary approach. At the same time attention is drawn to
      the limitations of his general outlook and to his political views, which in their
      historical context carry disturbing overtones of proto-fascism. It does not
      detract from the value of his work as a clinical scientist to conclude that his
      philosophical amblyopia, allied to an ineradicable chauvinism that was shared by
      many Germans of his class and status, resulted in a failure to demarcate the
      boundaries of his professional expertise and distorted his judgment on the wider
      implications of his own achievements. The lessons for the theory and practice of
      psychological medicine are briefly discussed.

PMID- 7578281
TI  - The neo-Kraepelinian revolution in psychiatric diagnosis.
AB  - New revisions of diagnostic categories have produced the most recent
      classification systems, namely DSM-IV and ICD-10. The diagnostic approaches
      exemplified by these two nomenclatures are very similar to one another and
      represent a return to descriptive psychiatry in which careful observation of
      symptoms, signs, and course of mental diseases become the diagnostic criteria
      themselves. In many ways, these newest classification schemata can be considered
      a return to phenomenological psychiatry perhaps best exemplified at the start of
      this century by Emil Kraepelin. Thus, recent developments in psychiatric
      diagnosis can be thought of as "neo-Kraepelinian". Because they represent a
      relatively radical change from psychodynamic approaches to evaluation and
      diagnosis, they can also be called "revolutionary." This paper traces the roots
      of current diagnostic systems and compares and contrasts these systems to the
      classification schema described by Kraepelin. Diagnostic criteria for
      schizophrenia are used as an example of how diagnostic conventions have changed
      dramatically over the past 50 years. Discussion of the implications of this neo
      Kraepelinian revolution in psychiatric diagnosis is included.

PMID- 7578282
TI  - Dementia praecox and manic-depressive insanity in 1908: a Grade of Membership
      analysis of the Kraepelinian dichotomy.
AB  - Grade of Membership (GoM) analysis, a multivariate classification technique based
      on fuzzy-set mathematics, was applied to the demographic, history, and mental
      state data on 53 dementia praecox cases and 134 manic-depressive insanity cases
      admitted to Kraepelin's University Psychiatric Clinic in Munich in 1908. The
      original data recorded by Kraepelin and his collaborators on special Zahlkarten
      (counting cards) were rated and coded in terms of the Present State Examination
      (PSE) Syndrome Check List. The statistical analysis resulted in a high degree of
      replication of Kraepelin's clinical entities. However, the dichotomy of dementia
      praecox and manic-depressive insanity was not fully supported. The catatonic
      syndrome tended to occupy an intermediate position between the two major
      psychoses. The possibility is discussed that catatonia in Kraepelin's time shared
      certain clinical features with the later diagnostic groupings of schizoaffective
      disorder, cycloid psychoses, and other "atypical" forms of psychotic illnesses.

PMID- 7578283
TI  - Inner connections within domain of dementia praecox: role of supervisory mental
      processes in schizophrenia.
AB  - Kraepelin's conclusion that there were underlying common features justifying the
      amalgamation of catatonia, hebephrenia and paranoia hallucinatoria to form a
      single illness is confirmed by factor analytic studies delineating the various
      dimensions of schizophrenic psychopathology. Neuropsychological studies reveal
      that the three cardinal dimensions reflect disorder of the supervisory mental
      processes responsible for initiation, selection and monitoring of self-generated
      mental activity. Brain-imaging studies indicate that the underlying
      neuropathology entails disordered functional connectivity within the neural
      networks in multimodal association cortex that are the substrate of the
      supervisory mental processes, consistent with Kraepelin's own speculation about
      the essential nature of the condition.

PMID- 7578284
TI  - Neuropsychology of schizophrenia according to Kraepelin: disorders of volition
      and executive functioning.
AB  - Emil Kraepelin was the first to identify schizophrenia as a distinct disease in
      1896. The purpose of this paper is to rediscover and reexamine the
      neuropsychology of schizophrenia according to Kraepelin. Kraepelin thought that
      the "dementia" of dementia praecox was primarily a disorder of volition, rather
      than one of intellect. "Volition" or "will" referred to the ability to make
      conscious decisions and to carry them out. By quoting relevant passages in his
      classic textbook, Dementia Praecox and Paraphrenia, the case is made that
      Kraepelin's detailed description of volitional deficits in patients with dementia
      praecox clearly documents impairments in executive functioning in schizophrenia
      patients during the preneuroleptic era. To a large extent, these deficits may be
      responsible for the "dementia" of dementia praecox and the "chronicity" of
      chronic schizophrenia. If this hypothesis is correct, the long-range prognosis of
      patients with schizophrenia may be considerably improved by treatment programs
      designed to facilitate executive functioning.

PMID- 7578285
TI  - Are mental diseases brain diseases? The contribution of neuropathology to
      understanding of schizophrenic psychoses.
AB  - Nearly a century after the seminal contributions of Emil Kraepelin, the search
      for neuropathologic correlates of schizophrenic psychoses continues. A multitude
      of neuroanatomic and neurochemical findings has emerged in recent years, but many
      of these findings are not replicated or are difficult to interpret in light of
      methodologic problems. In this review replicated neuropathologic and neuroimaging
      studies are discussed. The hypothesis that emerges from these studies is that
      schizophrenia is a developmental abnormality affecting the connectivity of the
      prefrontal and medial temporal cortices.

PMID- 7578286
TI  - Emil Kraepelin and comparative sociocultural psychiatry.
AB  - Emil Kraepelin, well known as the principal designer of modern psychiatric
      nosology, is less well known for his pioneering work in comparative sociocultural
      psychiatry. This paper is trying to document Kraepelin's role as the inaugurator
      of systematic investigations into culture-dependent differences in
      psychopathology. Despite his many responsibilities as clinician, teacher,
      hospital administrator and scientific author, Kraepelin considered cross-cultural
      comparison of such importance that he spent considerable time on the preparation
      of then very cumbersome overseas expeditions. His first research journey in 1904
      to Southeast Asia led to the programmatic formulation of comparative psychiatry
      as a scientific endeavour designed to contribute to the better understanding of
      psychopathological processes and to a comprehensive comparative ethnopsychology
      ("Voelkerpsychologie"). Kraepelin's main cross-cultural research project, planned
      to extend to seven non-European countries and to involve many foreign colleagues,
      was prevented by World War I and postwar complications. One year before his
      unexpected death, Kraepelin conducted comparative studies with American Indian,
      Afro-American and Latin American patients at psychiatric institutions in the
      United States, Mexico and Cuba in 1925. In his writings Kraepelin commented on
      certain differences in the incidence and presentation of psychopathological
      phenomena that he considered to be due to ethnic-cultural characteristics or
      social conditions. This paper discusses in detail Kraepelin's observations on the
      pathoplastic and pathogenic effects of cultural and social factors, and
      demonstrates the influence of his ideas on the development of modern social and
      transcultural psychiatry.

PMID- 7578287
TI  - Personality antecedents of alcoholism in a national area probability sample.
AB  - Kraepelin viewed alcoholism as a symptom complex caused by heritable individual
      differences in emotional predisposition and volitional control. Recent clinical
      and genetic research has distinguished subtypes of alcoholics with different
      personality traits, symptoms, course, mode of inheritance, and response to
      treatment. The heritable personality traits that influence the initiation,
      continuation, and severity of alcoholism were examined by interview of a national
      area probability sample of 1019 non-institutionalized adults across the
      continental United States of America. We found that harm avoidance inhibits the
      initiation and frequency of drinking, but increases the risk of developing
      problems once frequent drinking has begun. Novelty seeking increases the
      initiation of drinking and the probabilities of frequent and problem drinking.
      This supports Kraepelin's description of the etiology and course of alcoholism as
      a symptom complex related to individual differences in emotional predisposition.

PMID- 7578288
TI  - Partners in adversity. V: Support, personality and coping behaviour at the time
      of crisis.
AB  - This paper presents further results from a study of married women in Edinburgh
      who had just suffered an adverse experience: either their husband's non-fatal
      myocardial infarction, their husband's death or their own arrival in a Women's
      Aid refuge for battered women. Interviews were carried out 4-6 weeks following
      the adverse experience and, where possible, again approximately 3 months later.
      Symptoms were assessed using the 30-item General Health Questionnaire and
      criterion-based measures of depression and anxiety derived from it. The extent
      and nature of crisis support from household members and from groups of people
      outside the household, and also of failures in expected support, was measured at
      first interview. A modified version of Tyrer and Alexander's (1979) personality
      schedule was administered at the follow-up interview, and the resulting
      personality data were then reduced to six factors using principal components
      analysis. An interviewer assessment of how well the subject was coping was made
      at both interviews. The vast majority of the sample received extensive practical
      and emotional support from family and friends, and perhaps because such positive
      support was so prevalent, variations in it seemed to have little effect on
      symptoms. However, subjects who were unexpectedly 'let down' or criticised by
      friends or family tended to show higher symptom levels, although, surprisingly,
      this was less true for the bereaved wives than for the others. The six
      personality factors that emerged were labelled nervousness (similar to
      neuroticism) impulsivity, social withdrawal, helplessness, inferiority and
      aggressiveness. There was evidence that subjects high on nervousness remained
      symptomatic longer following the adverse experience. The aggressiveness factor
      showed a curvilinear trend with high and low aggressives showing higher symptom
      levels than middle aggressives. However, for the coronary wives the trend was
      linear with low aggressives having high symptoms. Subjects low on impulsivity
      were more affected by being 'let down' by friends and family. The interviewer
      assessed coping measure was linearly related to nervousness and showed a
      curvilinear relationship with aggressiveness.

PMID- 7578289
TI  - Prenatal exposure to influenza epidemics and risk of mental retardation.
AB  - This study was undertaken to determine whether prenatal exposure to influenza
      epidemics increases the risk of mental handicap. The monthly birth frequencies of
      827 first-admission individuals (mean age at admission 13 years) with a primary
      diagnosis of non-specific mental retardation, discharged from psychiatric
      hospitals in England and Wales, were examined in relation to the monthly death
      rates from influenza over the period 1953-1980. The relative risk of developing
      mental handicap when exposed to influenza epidemics during mid-gestation was
      assessed by a generalized linear model. Increased death rates from influenza, a
      measure of prevalence of the infection, were significantly associated with an
      increase in births of mentally handicapped individuals 6 months later. For every
      1000 female deaths from influenza there was a 17% increase in births of mentally
      handicapped individuals 6 months later. Maternal exposure to influenza at
      approximately the third to fourth month of gestation may be risk factor for
      developing mental handicap.

PMID- 7578291
TI  - Comments on Takei et al.: Prenatal exposure to influenza epidemics and the risk
      of mental retardation.

PMID- 7578290
TI  - Comments on Takei et al.: Prenatal exposure to influenza epidemics and the risk
      of mental retardation.

PMID- 7578292
TI  - Comments on Takei et al.: Prenatal exposure to influenza epidemics and the risk
      of mental retardation.

PMID- 7578293
TI  - A second case of schizophrenia in the family: is it observed differently?
AB  - Comparing reports on emerging symptomatology of schizophrenia by families with
      and without a prior case of the disorder shows that experienced families are more
      sensitive to delusions and hallucinations; however, they observe unspecific,
      affective, negative, and social/behavioral symptoms less adequately than
      relatives who have no previous case of schizophrenia in their families. The
      results only partly support the hypothesis that already-affected families tend to
      deny a second case. A contrast effect of the first psychosis over the second case
      (as long as it is prepsychotic) appears to be plausible also.

PMID- 7578295
TI  - Gastric antral vascular ectasia (watermelon stomach)
AB  - With the invention of fiberoptic endoscopy and now video endoscopy, evaluation of
      gastrointestinal bleeding has dramatically changed the understanding and
      treatment of vascular malformations. Gastric Antral Vascular Ectasia is one such
      rare entity that is known to cause acute or chronic blood loss. The term
      "watermelon stomach" represents the endoscopic appearance of bright red
      longitudinal stripes localized in the gastric antrum, thus, resembling the skin
      of a ripened watermelon. Definitive treatment of watermelon stomach is
      antrectomy. However, endoscopic modalities offer an effective, relatively safe,
      and clearly less invasive treatment option for patients who experience acute,
      recurrent or chronic gastrointestinal bleeding from these lesions. In this
      article, the author describes the characteristics, diagnosis, and treatment of
      this uncommon disorder.

PMID- 7578296
TI  - Reusable biopsy forceps: a cost-effective measure for the endoscopy suite.
AB  - Some healthcare practitioners have recommended the use of disposable medical
      accessories as standard practice. Advantages of using disposable medical
      equipment include the potential for infection prevention, convenience, and
      decreased reprocessing and storage costs. Disadvantages of reusable accessories
      include the initial cost, "down time" required for repair and, most importantly,
      the potential for spreading infection. In this study, the investigators provide a
      cost analysis of reusable biopsy forceps for a 12-month period from April 1993
      through March 1994. This prospective, descriptive study evaluated purchase price,
      number of uses, repair history, and cleaning costs for reusable biopsy forceps
      used in the endoscopy unit of a large multi-specialty clinic. Results of the
      study revealed that the reusable biopsy forceps became cost-effective after seven
      uses.

PMID- 7578297
TI  - Low profile gastrostomy devices.
AB  - Many styles of gastrostomy tubes have been developed and used over the years by
      patients requiring long-term enteral feedings. As an alternative to the use of
      the traditional gastrostomy tube, the low profile gastrostomy device (LPGD) was
      introduced in the mid-1980s. The purpose of this article is to provide an
      historical overview of gastrostomy tubes and the LPGD. The authors will highlight
      advantages and limitations of the two main types of LPGDs. Teaching guidelines
      are included. Nurses who possess a strong knowledge base on the latest trends in
      low profile gastrostomy devices will be better prepared to educate patients,
      family members, and caregivers.

PMID- 7578294
TI  - Future of AHCPR threatened.

PMID- 7578298
TI  - Enterococcal nosocomial infection: epidemiology and practice.
AB  - Caring for patients susceptible to enterococcal infections is a part of practice
      for nurses working in today's hospital units. While enterococci are not
      particularly virulent organisms, they are well suited to causing infection in
      hospitalized patients, especially in the very old, the seriously ill, and the
      immunosuppressed. Despite increased understanding of the clinical threat posed by
      multiresistant strains of enterococci, the incidence of nosocomial enterococcal
      infection is growing. In this article the author examines the epidemiology and
      risk factors for colonization and infection with enterococcal bacteria and
      provides a brief review of antibiotic sensitivities for the organisms. A case
      study illustrates the course and consequence of infection with multiresistant
      enterococcus for the seriously ill patient. The importance of education of health
      professionals in prevention and control of enterococcal infection and
      superinfection is discussed.

PMID- 7578299
TI  - A clinical pathway for endoscopy.
AB  - The purpose of this article is to describe the development and use of a clinical
      pathway in an endoscopy setting. The goal was to incorporate all of the
      established practices of each discipline--nursing, medicine, admissions,
      laboratory, radiology, and others--without changing their practice models. The
      clinical pathway is the framework for all the activities in the management and
      practice of the unit, including the nursing standard of care, nursing competency
      based practice, hospital policy and procedures, quality improvement, risk
      management, and physician preference.

PMID- 7578300
TI  - A case history of my most interesting patient.

PMID- 7578301
TI  - Just a droplet in the bucket.

PMID- 7578302
TI  - Pharmaceutical intervention in diabetes management.
AB  - Insulins and oral agents should be prescribed based on the assessed needs and
      physical status of the patient. They are most effective when combined with a
      diabetes management plan which will include 1) an individualized nutrition plan,
      2) an exercise plan based on the assessed physical need and capabilities of the
      patient, 3) consistent self-blood glucose testing, and 4) patient understanding
      of correct medication/insulin administration, effect, and side effects. All
      aspects of communication between the health team and the patient need to be clear
      and concise if the patient is to reach self actualization in diabetes management.

PMID- 7578303
TI  - Female prostitutes in south London: use of heroin, cocaine and alcohol, and their
      relationship to health risk behaviours.
AB  - The present study looks at the association between drug and alcohol use and
      sexual risk behaviours in a sample of 51 women who were currently working as
      prostitutes and also currently using opiates and/or stimulants. Most women
      reported regularly using condoms with clients but a substantial minority
      sometimes had unprotected sex with clients. There was no overall association
      between any of the drug use variables (including the use of crack cocaine) and
      the likelihood of unprotected sex. The use of drugs appears to have affected the
      sexual practices of different women in different ways: a substantial minority
      (just under a quarter of the sample) reported that for them, drug use did reduce
      the chances that they would use a condom. There was a link between willingness to
      have unprotected sex for more money and drinking larger amounts and drinking more
      often. The results also indicate that these women were exposed to a variety of
      health risks, including sharing injecting equipment and having unprotected sex
      with their regular partner who was often a current or former drug injector. A sub
      sample (n = 34) completed a confidential questionnaire which showed that one
      third had previously had at least one sexually transmitted disease and 15% of
      them had been infected during the previous year. These findings about rates of
      STD infection raise questions about the extent to which self-reported condom use
      by prostitutes can be used as an indicator of actual levels of infection risk.

PMID- 7578304
TI  - Unconventional conceptions and HIV.
AB  - The condom is widely recommended as the principal method for preventing HIV
      transmission, but such advice obviously does not apply to women who are seeking
      to become pregnant. In this sense, 'safer sex' is incompatible with reproduction.
      Existing research into HIV transmission has examined the choices made by those
      wishing to conceive within a sexual relationship; such research shows that HIV is
      not a highly significant factor in their decision-making processes. This study
      aims to extend the debate by exploring the decision-making processes of women
      seeking to become pregnant with donated sperm. In particular, we focus on women
      outside the fertility clinic system who do not have access to sperm screened for
      HIV to see whether HIV is a significant factor in these women's decisions. The
      study involved in-depth interviews with 20 women (14 lesbians, one bisexual and
      five heterosexuals) recruited through informal networking and snowball sampling.
      HIV was a salient concern for our sample, largely because of their contacts with
      gay men, but nonetheless most of these women took some risks. On the one hand,
      the conscious deliberations necessary to conceive through self-insemination
      facilitated risk reduction, as did factors such as 'stranger-danger'. On the
      other hand, factors such as the scarcity of suitable sperm donors and the women's
      own feelings of gratitude and loyalty to their donors mitigated against their
      requesting that their donor take an HIV test. This study highlights the need to
      provide information for women seeking self-insemination, and to remove
      restrictions on access to fertility clinics, in order to reduce their risk of HIV
      infection and subsequent vertical transmission.

PMID- 7578305
TI  - Risky heterosexual practices amongst women over 30: gender, power and long term
      relationships.
AB  - Statistics suggest that older and younger people are about equally at risk for
      HIV infection, yet existing research on heterosexuality and safer sexual
      practices has tended to focus on people under the age of 25. The present
      qualitative study investigates risk behaviours and the practice of safer sex in
      older populations. Group discussions comprising women over the age of 30 (n = 23)
      targeted two issues: the gendered power dimension of heterosexuality and safer
      sex in long term relationships. Cohort issues were also discussed. The discussion
      groups revealed that the imbalance of power between men and women which has been
      shown by previous research to constrain younger women's choices with regard to
      safer sex, continues to affect older women's decisions. Many of the group
      participants still found it difficult to assert themselves in sexual
      relationships and even those who were able to challenge overt pressures to engage
      in unsafe sex were still susceptible to internalized social pressures. In
      addition, it seems that risks for older age groups are increased by difficulties
      in continuing to use condoms in long term relationships where monogamy cannot be
      taken for granted. It was also apparent that there are difficulties in changing
      sexual behaviours which were established before HIV became an issue.

PMID- 7578306
TI  - Perceived function of and barriers to condom use in Arusha and Kilimanjaro
      regions of Tanzania.
AB  - This paper presents data from a population-based survey which assessed perceived
      function of and barriers to condom use among the adult population aged 15-54
      years in the Arusha and Kilimanjaro regions in northern Tanzania. A structured
      questionnaire was used in data collection. A total of 1081 people participated in
      the study, representing a response rate of 67% of the eligible population from
      two urban and two semi-urban communities. Of the 1081 respondents, 69.9% knew
      what condoms were and of these 55.3% stated that condoms are used for
      contraception while 24.2% reported that condoms are used for prevention of
      AIDS/STD. Among those who knew about condoms, 11.2% stated that they disliked
      using condoms during sexual intercourse while 18.7% felt that condoms reduced
      sexual enjoyment. Furthermore, 34.1% of the respondents reported that they would
      not supply condoms to their sexually active children. Respondents who reported
      that condoms reduced sexual enjoyment as well as those who stated that they
      disliked using condoms were significantly less likely to use condoms than those
      who stated otherwise. These data indicated the underlying psychosocial barriers
      to condom use among the respondents and hence the need for further research and
      specific health education strategies to overcome them. Priority areas for
      intervention research are suggested.

PMID- 7578308
TI  - In-patient care for symptomatic, HIV-infected persons: a longitudinal study of
      hospitalizations, in-patient drug use, and related costs.
AB  - Patterns in the costs of hospital in-patient care and in-patient drug treatment
      of 121 symptomatic, HIV-infected patients are described for a university hospital
      between 1987 and 1991. Trend analyses have been performed on quarterly and yearly
      data using parametric and non-parametric statistical techniques. During the 5
      year study period the demand for hospital beds almost quadrupled despite a
      constant number of admissions per person-year and a 40% decrease in the average
      length of stay. The demand for beds was highest in the autumn and winter months.
      The impact of female and/or heterosexual subgroups on the yearly utilization of
      resources increased and reasons for hospitalization became more diverse; there
      were fewer hospitalizations for Pneumocystis carinii pneumonia infection.
      Antimicrobial drug treatment accounted for the increased drug treatment costs.
      The implications for AIDS-treating specialists, hospital managers, and scenario
      analysts are discussed.

PMID- 7578307
TI  - Reliance by gay men and intravenous drug users on friends and family for AIDS
      related care.
AB  - A group of gay-identified men (n = 81) and intravenous drug users (n = 88)
      diagnosed with AIDS in San Francisco were interviewed regarding their use of
      friends and family to meet their care needs. Analytic of quantitative data
      revealed that gay men relied more than did IDUs on friends for care. Neither
      group relied primarily on their families for care. Analysis of the qualitative
      data identified five primary barriers to care. First, many people with AIDS are
      not accustomed to asking for help and often avoid it when possible. Second, the
      social stigma surrounding AIDS sometimes leads to isolation. Third, some people
      with AIDS have kin with health problems of their own, thereby sometimes
      compromising this potential source of care. Fourth, the AIDS epidemic has
      devastated identifiable sub-populations, leaving surviving members of these
      groups emotionally exhausted and sometimes unable to provide as much help as they
      might have liked. Finally, some respondents choose to voluntarily cut themselves
      off from 'supportive' relationships that they perceive to be destructive now that
      they have been diagnosed with a fatal illness. Professional care providers and
      health care planners should be aware of dynamics within informal care networks of
      people with AIDS that may leave patients without necessary care.

PMID- 7578309
TI  - Friends and lovers: needle sharing in young people in Western Australia.
AB  - The Youth AIDS and Drugs (YAD) Study is a study of young people who inject drugs,
      and their risk of the transmission of HIV through needle sharing and/or unsafe
      sex. One hundred and five people, aged less than 21, 75% of whom were current or
      recent injectors, undertook in-depth interviews which were tape recorded,
      transcribed and analysed qualitatively. This paper focuses on the ways in which
      the young people in the group attempted to manage the risk of needle sharing.
      Needle sharing in the study group was not common behaviour. Almost all injectors
      employed one of four major Risk Management Strategies some of which included the
      possibility of sharing unbleached needles with a friend or a lover. These
      strategies were strongly related to beliefs that such friends and lovers were
      well enough known by the individual for there to be very little risk. The
      implications of these findings for health promotion with young people who inject
      drugs in Perth, a city of low IDU seroprevalence, are outlined.

PMID- 7578310
TI  - Unmet needs for help among persons with AIDS.
AB  - Current trends in AIDS care in the United States, including dehospitalization and
      improved outpatient treatment, may place many persons with AIDS (PWAs) at
      increased risk for having unmet need for help with daily living demands. Using
      interviews with 224 PWAs, we examined the prevalence and correlates of unmet need
      for assistance across six functional domains: personal care, instrumental
      activities of daily living (e.g. home chores, using transportation), social
      functioning, role performance, taking care of one's health and negotiating
      systems. Overall, 74.1% of respondents reported having either a partially or
      completely unmet need for help in one or more areas of functioning. Unmet need
      for help was highest for instrumental activities of daily living (46.4%). Unmet
      need was associated with illness severity (i.e. more symptoms and
      hospitalizations), minority status and support network characteristics
      (proximity, size and type of supporters). Implications of unmet needs data for
      improving the clinical care of PWAs are discussed.

PMID- 7578312
TI  - Somatic care wanted by HIV-infected intravenous drug abusers: the patients'
      opinions and experiences.
AB  - The somatic care of HIV-infected intravenous drug abusers (IVDUs) is often
      combined with many problems. The addict is often an unpopular patient, but
      society must assume responsibility for him or her and it is important to solve
      care problems in an appropriate way. This study was undertaken in order to
      investigate what kind of care addicts want when they become somatically ill. A
      questionnaire was given to patients who acquired HIV infection due to intravenous
      drug abuse, who visited an outpatient clinic for HIV-infected patients at the
      Department of Infectious Disease, Huddinge Hospital, Stockholm, Sweden. A total
      of 72 of the original 78 questionnaires could be evaluated. Thirty respondents
      took part in the Stockholm Methadone Programme. The patients were asked to rank
      the importance of professional competence among the staff. The patients ranked
      competence in pain treatment highest followed by competence in somatic medical
      care. Lower ranked, but still perceived as important, was competence in
      psychiatric medical care and social welfare work. Experience in treatment of
      addiction was ranked as less important. It can be concluded that it is fruitful
      to ask IVDUs about their preferences concerning care.

PMID- 7578314
TI  - WHO Global AIDS Statistics.

PMID- 7578311
TI  - Women and AIDS in Zambia: a review of the psychosocial factors implicated in the
      transmission of HIV.
AB  - Women are at high risk for HIV infection in Zambia. There are several
      interrelated factors to account for this including the economic, cultural and
      educational status of women. This paper explores these factors and suggests that
      these factors need to be thoroughly understood before preventive strategies are
      designed and implemented.

PMID- 7578313
TI  - Guidelines for counselling adolescents with haemophilia and HIV infection and
      their families.
AB  - Adolescents, poised between childhood and adulthood, and their families have many
      challenges. It is timely to review what these are for those with haemophilia, HIV
      and HCV (hepatitis C) infection in the 1990s. All three conditions are life long,
      life threatening and incurable. The main dilemmas facing these families are how,
      when and who should tell the adolescent about HIV and HCV; getting the right
      balance between the realities of the infections, the best interests of the
      adolescent and the risks of transmission of infection to others. HIV interrupts
      the adolescent's normal life stage expectations and development. How health
      carers relate to the adolescent is influenced by the split responsibilities to
      the adolescent and his parents as well as to others who might be at risk of
      infection. Clarity about the issues related to medical treatment and care,
      disease progression, and enhancing skills in dealing with families and young
      people are ways of helping to maintain hope in the face of life threatening
      illnesses for all concerned.

PMID- 7578316
TI  - [Thermodynamic basis for the water-bridge structure of collagen].
AB  - A solution of the problem of topology of hydrogen bond net in a triple-helix of
      collagen is suggested on the basis of thermodynamic data on denaturation of
      phylogenetically different collagen, as well as on that of the earlier evaluation
      of the energy of OH-group 4-hydroxyproline bond. It is shown that only water
      bridged collagen structure in the variant of Ramachandran school can explain both
      the change of thermal stability upon the extent of proline hydroxylation and the
      phylogenetic change of thermostability.

PMID- 7578315
TI  - [Global optimization of the conformational energy of oligopeptides using a tunnel
      algorithm].
AB  - The tunneling algorithm has been suggested as a method for the searching of the
      low energy conformations of the oligopeptides. The efficiency of the method has
      been compared with other global energy minimization methods such as grid search
      and molecular dynamics. It has been shown that tunneling algorithm reached global
      minimum of potential energy of the molecule of 3-4 residues more effectively than
      other methods. Experiments with oligopeptides of more than 4 residues showed that
      although during reasonable time tunneling algorithm does not reach the global
      minimum it can very effectively find the low energy minimum.

PMID- 7578317
TI  - [Molecular mobility and electrical properties of keratin].
AB  - The samples made from the horn of Saiga tatarica were investigated by PMR method.
      It was shown that an increase of mobility of adsorbed molecules correlated with
      the appearance of the peaks of thermally stimulated currents of depolarization in
      the region of 370 K-390 K. The activation energies of molecular mobility in
      keratin were found.

PMID- 7578318
TI  - [Classical and pulsed gel electrophoresis of biopolymers. Theory and
      applications].
AB  - The work is devoted to the modern theory of gel electrophoresis in stationary and
      alternating electric fields, and it brings together results of numerous
      theoretical and experimental studies hitherto conducted. Main attention is drawn
      to the approximation definitions used in theory and to cases of divergences
      between theory and experimentation. Basic methods of gel electrophoresis and
      electrotransfer are principally analysed that appeared not long ago and showed to
      be greatly perspective. The resolution ability, advantages and disadvantages of
      pulsed methods are analysed, methods and instrumentation used in laboratory
      practice are described. Quantitative assessment of most important dependencies of
      applied significance are shown.

PMID- 7578319
TI  - [Effect of temperature on polarity of an annular and bilayer synaptic membrane
      lipid].
AB  - Using fluorescent probe pyrene a study was carried out of temperature dependence
      of the annular and lipid bilayer polarity in synaptic membranes. Polarity of
      microenvironment was evaluated by a ratio of intensities of vibronic bands in
      pyrene fluorescence spectra at direct excitation of probe or through energy
      transfer from protein molecules. At the temperature range 10-50 degrees C the
      polarity of bilayer was shown to increase while that of annular lipid underwent
      biphasic changes. Above 20 degrees C polarity of the bilayer was higher than of
      the annular zone. From experiments on pyrene fluorescence quenching with
      potassium iodide the conclusion has been made that changes in polarity correlate
      with pyrene accessibility to water.

PMID- 7578321
TI  - [Mathematical modeling of the mechanism of cilia motion: an internal hydrodynamic
      drive].
AB  - A physical approach to the description of the motion mechanism of cilia based on
      the importance of hydrodynamical interactions between the intraciliary
      microstructures is proposed. The motion of the cilium model was investigated
      theoretically. A mechanism of synchronization of cilia beating in metachronal
      waves is proposed.

PMID- 7578320
TI  - [Interconnection between the two-stage kinetics of actomyosin Mg2+-ATPase and
      breaks in Arrhenius plots].
AB  - It has been shown that breaks in Arrhenius plots take place only when the two
      stage mechanism of actomyosin ATPase is realized. Removal of two-stage behavior
      of ATPase leads to the strengthening of Arrhenius plots. It can be achieved by
      decomposition of two-stage kinetic curves into two one-stage (higher and lower
      temperature) constituent curves, or by "switching off" ATPase reaction over one
      of the two one-stage mechanisms by changing KC1 or ATP concentrations. In both
      cases Arrhenius plots are linear and Ea values, as well as maximal ATPase
      activity for higher temperature mechanism are twice as much as those for the
      lower temperature mechanism. On the contrary, non-linear Arrhenius plots show the
      lowering of Ea with an increase of temperature. We conclude that the breaks in
      Arrhenius plots can be due to the shift of equilibrium between two one-stage
      mechanisms of actomyosin ATPase, whose simultaneous course leads to the two-stage
      kinetics of this reaction.

PMID- 7578323
TI  - [A computer model of "sense of humor". I. General algorithm].
AB  - A computer model of "a sense of humor" is formulated. The humorous effect is
      treated as a specific malfunction in the processing of information conditioned by
      the necessity of a quick deletion from consciousness of a false version. The
      biological function of a sense of humor consists in quickening the transmission
      of processed information into consciousness and in a more effective use of brain
      resources.

PMID- 7578325
TI  - [The rule of Roux and microvascular bifurcations].
AB  - The article deals with an attempt to explain the non-observance of Roux's role
      for configurations of microvascular bifurcations with the help of the hypothesis
      on quantum character (partial) of haemodynamics through a bifurcation. Influence
      of low preservation impulse and viscosity of the blood movement was shown on the
      configurations of the vascular bifurcations.

PMID- 7578324
TI  - [A computer model of "sense of humor". II. Realization in neuronal nets].
AB  - The Hopfield model of neural networks can be adapted for solving the "linguistic
      problems", i.e. the processing of a continuous succession of polysemantic images.
      The realization of "a sense of humor" in such a model is possible.

PMID- 7578322
TI  - [Structural changes in erythrocyte membranes in diabetes mellitus using spin
      labelled fatty acids].
AB  - Microviscosity and polarity of erythrocyte membranes of the blood of patients
      suffering from diabetes were studied by ESR using spin-labeled fatty acids.
      Structural changes were discovered 0.6-0.8 nm from the membrane surface in the
      lipid bilayer of erythrocytes obtained from patients' blood. No essential
      immobilization of the acyl chains of phospholipids was found in deeper layers as
      compared with the control. The bilayer polarity at different depth was not
      essentially changed either.

PMID- 7578327
TI  - [Generation of a nerve impulse as a process in plasma. I. Volt-ampere
      characteristics of membrane contact].
AB  - A theory of the nervous impulse generation is proposed. It is based on the plasma
      (electrolyte) properties near the half-penetrated contact of the regions with
      different ions concentration. The main processes considered in this theory are
      following: a change of K+ ions concentration and diffusion of these ions near the
      outward membrane surface. A correlation between the electric current flux through
      the contact and the potential difference on this contact is obtained from the
      solution of the steady-state diffusion equation.

PMID- 7578326
TI  - [Assessment of the possibility of using the photodynamic effect in rheumatology].
AB  - Results of the analysis of a number of parameters which determine the efficiency
      of using the photodynamic action for treating rheumatoid arthritis are reported.
      The investigations are based on determining the character of sensitizer
      stabilization in the joint tissue and evaluating its stability. As the sensitizer
      chlorin e6 was chosen. We have established the fact of contrast accumulation of
      chlorin e6 in the synovial membrane and cartilage, developed the system of
      intrajoint introduction of the pigment, studied the kinetics of sensitizer
      destruction under irradiation.

PMID- 7578329
TI  - [A new model describing the isolation of fluorocarbons from an organism:
      dissolution of fluorocarbons in the lipid components of blood].
AB  - Perfluorodecalin (PFD), intravenously administrated to rabbits in the form of
      submicron emulsion, quickly disappears from the blood stream and accumulates in
      the liver, spleen and bone marrow. The expiration rate of PFD from the body can
      be significantly enhanced by intravenous administration of sunflower oil
      emulsion. It is supposed that the limit stage of PFD excretion is a fluorocarbon
      transport from accumulatory organs to the lungs by lipid carriers (lipoproteins,
      chylomicrons and cell membranes) in which fluorocarbons are physically dissolved.

PMID- 7578328
TI  - [Generation of a nerve impulse as a process in plasma. II. Stability of volt
      ampere characteristics of membrane contact].
AB  - Fluctuative changes of K+ ions concentration near the outward membrane surface
      are considered. Conditions of the excitement initiation on the membrane contact
      are determined from the solution of the unsteady-state diffusion equation. The
      values of the threshold potential and characteristic time of the nervous impulse
      development are obtained. The theory fits well with the experimental results.

PMID- 7578332
TI  - [Biotics of human blood after applying microcurrents].
AB  - By affecting man's acupuncture points by microcurrents the release of
      biologically active substances into the blood is stimulated which in its turn
      must be accompanied by a change in microelements composition. Concentrations of a
      number of microelements of the blood are determined by different biophysical
      methods before and after electropuncture. Concentration of elements with
      alternating valency decreases, while that of alkaline ones somewhat increases in
      the same blood samples of a healthy man. Thus the electropuncture stimulation
      regulates homeostasis of microelements in the blood.

PMID- 7578330
TI  - [Effect of ionizing radiation on cell membrane proteins].
AB  - The effect of ionizing radiation on the meat cattle thymocytes plasma membranes
      was studied. Using fluorescence quenching technique the effect of irradiation on
      proteins conformation was investigated. The influence of ionizing radiation on
      the plasma membranes was shown to be followed by changes of the protein structure
      dynamic organization.

PMID- 7578334
TI  - [X-ray fluorescent study of the ionic composition of lysozyme crystals].
AB  - The method of the studying of the ionic content in the protein crystals by X-ray
      fluorescence spectroscopy is proposed. The ionic content of the tetragonal
      glutaraldehyde--cross-linked lysozyme crystals in the 2- 11 pH range and upon the
      low and high ionic strengths is studied. The acid-base titration of the lysozyme
      crystals is carried out for determination of the pH-dependence of the net charge
      of the lysozyme molecule within protein crystal. It has been shown that ionic
      content in the protein crystal channels is determined mainly by the Donnan
      potential. The specific binding of the bromide-ions with lysozyme molecules is
      revealed and possible binding sites are discussed.

PMID- 7578331
TI  - [Oscillation of hemoglobin forms during blood storage].

PMID- 7578335
TI  - [Self-association of deoxytetraribonucleoside triphosphates d(TpGpCpA) in an
      aqueous solution by 1H NMR spectroscopy].
AB  - Self-association of deoxytetraribonucleoside triphosphate 5'-d(TpGpCpA) molecules
      in aqueous solution has been studied by one-dimensional and two-dimensional 1H
      NMR spectroscopy (500 MHz). Two-dimensional homonuclear PMR spectroscopy (2D-COSY
      and 2D-NOESY) was used for complete assignments of tetranucleotide proton
      signals. Concentration and temperature dependences of d(TpGpCpA) proton chemical
      shifts have been measured. Experimental results have been analyzed using dimer
      model of molecules association. Equilibrium association constant, values of
      limiting chemical shifts of tetranucleotide protons in the associate and
      thermodynamic parameters delta H and delta S of the association reaction have
      been determined. Comparative analysis of self-association characteristics for
      d(TpGpCpA) and its isomeric deoxytetranucleotide d(ApGpCpT) has been made.

PMID- 7578333
TI  - [Surface potential energy of peptides and conformation of amino acid residues in
      proteins. Preliminary results of processing using databank protein structures].
AB  - The fact of enzymatic synthesis of a protein polypeptide chain have been
      mentioned. The potential energy surfaces of peptides have been analysed. Based on
      the obtained results and characteristic peculiarity of the enzymatic reactions
      have been concluded that the non-glycine residues in a three-dimensional (3-D)
      protein structure most likely should be in the negative conformations. The
      analysis of the amino acid residue conformations have been performed on the 185 3
      D protein structures obtained by the X-ray crystallography at high resolution. It
      has been shown that the changes in the protein surrounding environment, in
      crystalline forms and functional state of protein, bindings of the ligands and
      inhibitors do not lead to the changes in the polarity of non-glycine residues
      conformational angles phi, and in the polarity of the conformational angles omega
      of all residues. Based on the results, 81 independent protein structures have
      been selected. The preliminary results of analysis of glycine and non-glycine
      residue conformations occurring in these structures have been presented.

PMID- 7578336
TI  - [The role of disulfide bridges of the residual protein in chromosomal DNA
      organization].
AB  - The review of literature data and our investigation on the role of disulfide
      bridges of residual protein (RP) in structural organization of chromosomal DNA is
      presented. It was studied the action of several S-S cleaving agents (2
      mercaptoethanol, dithiothreitol, NaBH4, glutathione reductase) on native DNA-RP
      complexes, isolating from the different eukaryotic and prokaryotic cells. It was
      shown, that the thiols result the fragmentation of DNA-RP complex in double
      strand subunits of several size (5 x 10(5), (18-20) x 10(6), 70 x 10(6) Da) on
      dependence of the incubate condition (concentration of thiols, pH, time). It was
      observed, that specific S-S bonds (thiol-sensitivity at neutral or acid
      conditions, glutathione reductase-sensitivity) are present in DNA-RP complexes,
      which may control of different structural levels of DNA into chromosome (gen
      transcription-replicon-domain). The possible quasisubunit structure of
      chromosomal DNA with participation of polypeptide S-S bonds and complementary
      "sticky" ends of subunits is discussed.

PMID- 7578337
TI  - [Intensification of the ionophoric effect of polymyxin M by free fatty acids.
      Dependence of the length of the fatty acid chain].
AB  - Mechanisms of potentiation of ionophoric effect of polymyxin M by free fatty
      acids was studied using measurement of electrical properties of bilayer lipid
      membranes. Among used unsaturated fatty acids the palmitic acid appeared to be
      the most effective. The obtained dependence of ionophoric effect of membrane
      antibiotic on the chain length of the fatty acid may be explained by the
      existence of the complex of special size appropriate to the membrane thickness.
      We suppose that free fatty acid and polymyxin M form the ion-conducting structure
      in lipid bilayer.

PMID- 7578338
TI  - [Chemiluminescence of low density lipoproteins activated by coumarin in the
      presence of divalent iron ions].
AB  - Physical-chemical properties of low-density human blood plasma lipoproteins have
      been studied using the chemiluminescence activated by the coumarin. The
      difference in the activated chemiluminescence of the native and oxidated
      lipoproteins can be seen in the fact that the amplitude of the quick flash is
      larger for the oxidated lipoproteins.

PMID- 7578341
TI  - [X-ray structural study of the effect of light on isolated bovine photoreceptor
      membranes].
AB  - The structure of multilamellar films prepared by air-drying of bovine retinal rod
      photoreceptor membrane suspension has been studied by means of small-angle X-ray
      diffraction methods. No reliable photoreceptor membrane structure modifications
      were observed with 100 s temporal resolution after the illumination of the film
      consisting of dark-adopted membranes. The comparative study of air-dried films
      prepared from dark-adopted and bleached photoreceptor membranes revealed no
      difference in their structures too. The structure alterations of photoreceptor
      membranes were recorded in the case of high (damaging) doses of visible light
      acting on photoreceptor membranes in suspension.

PMID- 7578339
TI  - [Kinetics of Fe2+-induced lipid peroxidation in liposomes in the presence of
      ascorbic acid. Concentrated effects of Fe2+ ions].
AB  - In order to study the kinetics of lipid peroxidation (LPO) at the stationary Fe2+
      concentration the measurement of 2-thiobarbituric acid-reactive substances
      (TBARS) accumulation along with chemiluminescence (CL) in liposomes in the
      presence of ascorbic acid was used. It was shown that at 1 mM concentration of
      ascorbic acid the constant rate of LPO development occurred. In this system the
      direct determination of LPO rates at different Fe2+ concentrations were
      performed. The dependence of LPO rate on Fe2+ concentration was bell-shaped with
      a maximum at 50 microM. Probably, this value corresponds the "critical" ferrous
      ions concentration in a system. At 500 microM Fe2+ the LPO development was
      completely inhibited, but the addition of inorganic phosphate was found to start
      TBARS accumulation and CL development. The increase of phosphate concentration up
      to 500 microM produced the increase of LPO rate, however, at a higher phosphate
      concentrations LPO rate decreased. The biphasic effect of phosphate was
      completely similar to the decrease of Fe2+ concentration from the initial level
      (500 microM). It was proposed that the effect of phosphate is due to Fe2+ ion
      chelation in water solution leading to the remove some part of membrane-bound
      ferrous ions participating in LPO reactions, rather than changing of Fe2+
      reactivity.

PMID- 7578340
TI  - [Formation and photosensitizing activity of protein tryptophanile photochemical
      breakdown products in isolated erythrocyte membranes].
AB  - Modification of photochemical processes in protein tryptophaniles of isolated
      erythrocyte membranes by chloroform was shown. It is established that formed in
      the presence of chloroform photoproducts are able to act as "internal"
      sensitizers of oxidation of membrane proteins and lipids when illuminated by UV
      light of ecological range.

PMID- 7578342
TI  - [Response of the rat erythrocyte glycolytic system to hyperosmotic shrinkage].
AB  - Hyperosmotic shrinkage (adding 300 microM sucrose to isotonic medium) stimulates
      lactate and ATP accumulation in rat but not human erythrocytes in which ATP pool
      was preliminary depleted. Inhibitors of Na(+)-K(+)-2Cl(-)-cotransport, Na+/H(+)-
      exchange and Na(+)- pump known to be activated by hypertonic medium had no
      influence on volume-induced effect. EGTA (1 microM), Ca(2+)-ATPase inhibitor
      vanadate (200 microM) and antagonist of calmodulin R24571 (10 microM) suppressed
      the stimulation of glycolysis by 80 and 30%, respectively. Addition of 1 microM
      Ca2+ and 1 mM Ca(2+)-ionophore A23187 in Ca2+ free medium stimulated glycolysis
      by 20% at isotonic conditions while additional hyperosmotic shrinkage resulted in
      a two-fold activation. It is suggested that shrinkage regulates activity of
      glycolytic enzymes through the mechanism of intracellular signaling involving
      Ca2+.

PMID- 7578343
TI  - [Change in certain physical characteristics of cells at various stages of the
      cell cycle].
AB  - Experiments on semisynchronized cultures of animal and plant cells, performed in
      our laboratory approximately 30 years ago, have demonstrated that there exist
      regular changes of certain physical parameters of the cells during the cell
      cycle. In particular on yeast cultures there has been observed the appearance of
      specific electron paramagnetic resonance (EPR) signals with simultaneous change
      of the static magnetic susceptibility of the cultures in the period immediately
      preceding the beginning of the intensive budding. On chlorella cultures grown at
      certain regimes of light and darkness it is possible to observe characteristic
      changes of the kinetics of the photoconduction signal at the frequency of 10 HHz
      (SHR-photoconduction). It can be conjectured that these effects are of a similar
      nature linked to some changes of the intracellular structures at certain stages
      of the cell cycle. The work performed much later makes it possible to link these
      changes to the appearance of spin, glass-like structures in macromolecular
      intracellular bodies.

PMID- 7578344
TI  - [Effect of radiation on erythrocyte membrane protein structure].
AB  - Influence of the 5 MeV electron beam on the structural dynamic organization of
      the protein phase of erythrocyte shadows has been studied by suppression of the
      tryptophane fluorescence of proteins by acrylamide. It has been observed that the
      irradiation leads to conformation changes and increase of the structural rigidity
      of the protein molecules.

PMID- 7578345
TI  - [Specificity of the effect of a super high frequency pulse-modulated
      electromagnetic field on evoked potentials of the cat visual, auditory,and
      sensomotor cortex upon stimulation with light and sound].
AB  - Effects of a pulsed-modulated superhigh frequency field (950 MHz, peak power of
      300 mkW/cm2 and 1.5 mW/cm2, pulse duration of 1 ms, single pulse irradiation
      mode, a pause between an electromagnetic pulse and an optic or auditory stimulus-
      20 ms) on the cat's brain evoked potentials were investigated in the optic,
      auditory and sensomotor cortex using acoustic and visual stimulation. It was
      established that during an exposure to electromagnetic waves with peak power of
      300 mkW/cm2 there were no reliable changes of the amplitude characteristics; but
      the amplitude of the auditory evoked potentials was reliably higher and the
      amplitude of the optic evoked potentials was reliably lower when they were
      affected by an electromagnetic field with peak power of 1.5 mW/cm2.

PMID- 7578348
TI  - [A simulated mathematical model of the blood coagulation system intrinsic
      pathway].
AB  - A mathematical model of the blood coagulation system intrinsic pathway is
      developed based on a reaction cascade scheme with two positive feedbacks. The
      model describes quantitatively well-known experimental data on blood plasma
      coagulation kinetics for various levels of activation and varying calcium
      concentrations. In the limit of experimental variety of the values of the rate
      for individual stages of coagulation cascade, obtained in [5-12], a good
      agreement with experimental data was shown for two discrete sets of the
      constants. The model relates unambiguously the threshold properties in
      coagulation activation by calcium with existence of the activation threshold. The
      model allows numerical estimates of the threshold activation values for various
      calcium concentrations. At calcium concentration of 0.2 mM, corresponding to
      normal calcium content in blood, the activation threshold is equal to 0.00016 nM
      and 0.0019 nM of Factor XIa for the first and the second sets of the system
      parameters, respectively.

PMID- 7578346
TI  - [Changes in the level, structure, and charges of rat serum lipoproteins during
      lengthy exposure to the cold].
AB  - The paper shows the results of complex investigation with the fluorescence
      techniques, electrophoresis a.o. methods of rat plasma lipoproteins in various
      terms (1 day-49 days) of cold exposure (+5 degrees C). There was the quantitative
      increase of the common fractions of VLDL and LDL to the 15 days of cold
      acclimation. The variations in percentage composition of LP occurred already on
      the first day. The changes of physico-chemical features of LP (surface charge and
      surface area, lipid viscosity and protein-lipid interactions did not always
      correspond to their quantitative changes and were not connected with lipid
      peroxidation. The decrease of the charges and the diminution of the surface area
      of VLDL, LDL and HDL were revealed on the first day. At 28-49 days the charges of
      VLDL and LDL were higher than in control, but LDL' one was lower. The occurred at
      this term decrease of efficiency of fluorescence energy transfer from LP'
      proteins to lipids, different variations of lipid viscosity demonstrated the less
      dip of proteins into lipids and/or the forming the aggregates of protein
      molecules. These in vivo LP modifications undoubtedly can induce the changes of
      their receptive and regulatory abilities.

PMID- 7578347
TI  - [Activation of Fe2+-induced chemiluminescence in human blood low density
      lipoproteins by the fluorescent dye C-525].
AB  - The effect of the fluorescent dye 2,3,5,6-1H,4H-tetrahydro-9-(2'-
      benzoimidazolyl)-quinolizin-(9,9a,1-gh)coumarin (C-525) on the chemiluminescence
      (CL) flash kinetics accompanying Fe(2+)-induced free radical lipid hydroperoxide
      decomposition in low density lipoproteins (LDL) have been studied. C-525 was
      found to increase CL flash intensity by a factor of more than 2000 at the
      concentration of 4 mkM without any influence on the CL kinetics. The mechanism of
      the CL amplification is apparently energy transfer from the primary excited
      product of lipid peroxyl radical recombination to fluorescent level of the C-525.
      A concentration dependencies of CL amplification degree by C-525 on the LDL
      concentration were revealed to be bell-shaped, so that for 0.01 mg/ml of LDL
      protein the maximum amplification degree was observed at 4 mkM of C-525, whereas
      for 0.02 mg/ml of LDL--at 8 mkM. For the elucidation of these effects the
      properties of C-525 as hydrophobic fluorescent probe have been used. The
      concentration dependencies of C-525 fluorescence in the LDL suspension were found
      to be similar to that of CL amplification by C-525. These data pointed to the
      fact that concentration dependencies of the CL amplification by C-525 was
      conditioned by its accumulation in a hydrophobic phase of lipoproteins, so that
      the effective dye concentration was determined by both the amount of C-525 added
      to the suspension and the concentration of LDL.

PMID- 7578350
TI  - [On the article by A.A. Smirnov "Hypothesis on the theory of the function of
      olfactory receptor cells"].

PMID- 7578349
TI  - [Hypothesis on the function of olfactory receptor cells].
AB  - The scientific studies of sensory systems (including olfactory organs) are
      carried out during a century. Usually a preliminary theory of object is suggested
      and detailed in accordance with the new data. However only the strong criticized
      theories of smell reception more than thirty) are now in the theoretical part of
      the olfactory organ physiology. The theory is necessary for planning the further
      investigations of olfactory organ; revealing the mystery of the biological
      sensors to improve the artificial ones; the improvement of the methods to obtain
      new biological active substances (perfume, drugs, insecticides). These
      circumstances justify the attempt to suggest the theory of the olfactory receptor
      cell functioning.

PMID- 7578351
TI  - Synthesis, hybridization properties, nuclease stability, and cellular uptake of
      the oligonucleotide--amino-beta-cyclodextrins and adamantane conjugates.
AB  - Synthesis of the oligonucleotides conjugated with amino derivatives of beta
      cyclodextrin and adamantane, at the 3'-end of host oligonucleotide, has been
      described. The oligonucleotide conjugates were examined for their nuclease
      stability, hybridization properties, and cellular uptake. The oligonucleotide
      conjugates had increased nuclease resistance compared to their parent
      oligonucleotides. Conjugation of adamantane to the oligonucleotides did not
      adversely affect the ability of the oligonucleotides to hybridize with their
      complementary RNA. Conjugation with amino derivatives of beta-cyclodextrin,
      however, significantly destabilized the duplex formation. In the cellular uptake
      studies, we found that amino derivatives of beta-cyclodextrin attached at 3'-end
      of the oligonucleotides did not help to increase the uptake by cells. Cellular
      uptake of oligonucleotide-adamantane conjugates in association with 2
      (hydroxypropyl)-beta-cyclodextrin (HPCD) as a "carrier" was significantly higher
      than that of control oligonucleotides.

PMID- 7578352
TI  - Biodegradable polymers for protein and peptide drug delivery.
AB  - We have reviewed a large cross-section of degradable polymeric delivery systems
      for protein and peptide pharmaceuticals. These systems include monolithic type
      devices in which the drug is dispersed throughout the polymer and protein-polymer
      conjugates where the drug is covalently bound to the polymer. These delivery
      systems have unique challenges associated with their development that are related
      to both protein stability and protein release kinetics. Despite numerous reports
      in the scientific literature which include many encouraging results in
      preclinical models, very few of these systems have been developed into viable
      products. The products that have made it to market, however, have proven to be
      very successful and demonstrate the significant advantages that these systems can
      provide. The continuous advances in biotechnology will produce more proteins and
      peptides that will be difficult to administer by conventional means, and an
      increased demand for controlled or site-specific delivery systems is anticipated.

PMID- 7578353
TI  - Synthesis and characterization of (d)NTP derivatives substituted with residues of
      different photoreagents.
AB  - Chemical cross-linking agents having a photoactivable azido group are promising
      for the study of the spatial organization of biopolymers. We describe here a
      variety of (d)NTPs derivatives (6a, 6b, 7, 11, 12, 14, and 16) bearing the
      residues of three different photoreagents containing an aromatic azido group (1a,
      2a, and 3a). These conjugates provide a wide choice of instruments to investigate
      nucleic acid-nucleic acid and nucleic acid-protein interaction. The synthesis of
      new photoreagent 2a has been also fulfilled. This compound is the most attractive
      for affinity modification of the nucleic acids.

PMID- 7578354
TI  - Galactose-containing amphiphiles prepared with a lipophilic radical initiator:
      association processes between liposomes triggered by enzymatic reaction.
AB  - A galactose-containing monomer (2-(methacryloyloxy)ethyl beta-D
      galactopyranoside, MEGal) was polymerized by using a lipophilic radical
      initiator. The amphiphile obtained formed a liposome by mixing with
      bis(trans,trans-2,4-dioctadecadienoyl)phosphatidylcholine (DDPC), and the
      liposome obtained was physically stabilized by the polymerization of DDPC by UV
      irradiation. The enzymatic treatment of the galactose-containing liposomes with
      galactose oxidase resulted in the formation of aldehyde groups on the liposome
      surface. By the subsequent mixing of the liposome suspension with the amino group
      containing liposome suspension, a rapid increase in turbidity was observed due to
      the formation of Schiff bases between the aldehyde groups and the amino groups at
      the interface of the liposomes. The rate of turbidity change strongly depended on
      the degree of polymerization of MEGal, the surface densities of galactose and
      amino groups on the liposome, the distance from the liposome surface to amino end
      groups, and the flexibility and deformability of the liposomes.

PMID- 7578355
TI  - Cobra venom factor immunoconjugates: effects of carbohydrate-directed versus
      amino group-directed conjugation.
AB  - Human IgM monoclonal antibody 16-88, derived from patients immunized with
      autologous colon carcinoma cells, was derivatized with two different cross
      linkers, S-(2-thiopyridyl)-L-cysteine hydrazide (TPCH), which is carbohydrate
      directed, and N-succinimidyl-3-(2- pyridyldithio)propionate (SPDP), which is
      amino group-directed. Two antibody functions, antigen binding and complement
      activation, were assayed upon derivatization with TPCH and SPDP. TPCH allowed for
      extensive modification (up to 17 TPCH molecules per antibody) without impairment
      of antigen binding activity, while this function was significantly compromised
      upon derivatization with SPDP. Antibody molecules derivatized with 16 SPDP
      residues showed almost complete loss of their antigen binding function. The
      complement activating ability of antibody 16-88 was significantly decreased after
      derivatization with TPCH or SPDP. In the case of SPDP derivatization, this
      decrease of the complement activating ability is predominantly a consequence of
      the impaired binding function. Upon conjugation of cobra venom factor (CVF), a
      nontoxic 137-kDa glycoprotein which is capable of activating the alternative
      pathway of complement, the antigen binding activity of SPDP-derivatized antibody
      was further compromised, whereas that of TPCH-derivatized antibody remained
      unaffected even after attachment of three or four CVF molecules per antibody. In
      both conjugates CVF retained good functional activity. CVF was slightly more
      active when attached to SPDP-derivatized antibody, suggesting a better
      accessibility of amino group-coupled CVF for its interaction with other
      complement proteins. These results indicate that carbohydrate-directed
      conjugation compromises the antibody function of complement activation, but
      allows for the generation of immunoconjugates with unimpaired antigen binding
      capability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578356
TI  - Preliminary study of the metal binding site of an anti-DTPA-indium antibody by
      equilibrium binding immunoassays and immobilized metal ion affinity
      chromatography.
AB  - Creating metal coordination sites by modifying an existing enzyme or by eliciting
      antibodies against metal chelate haptens is of great interest in biotechnology to
      create enzyme catalysts with novel specificities. Here, we investigate the metal
      binding potential of a monoclonal antibody raised against a DTPA-In(III) hapten
      (mAb 734). We study its relative binding efficiency to metals of biological
      relevance by equilibrium binding immunoassays and immobilized metal ion affinity
      chromatography, two approaches which can give complementary information regarding
      composition and/or structure of the metal binding site(s). Fe(III), Fe(II),
      Cu(II), Mg(II), Ca(II), and Zn(II) binding was compared to In(III). All of them
      were shown to displace indium, but their affinity for mAb 734 decreased by 100
      fold compared to indium. Competitive metal binding immunoassays between Zn(II)
      and In(III) revealed an unusual behavior by Zn(II) which remains to be explained.
      Moreover, IMAC allowed us to predict the metal binding amino acids involved in
      the antibody paratope. The antibody metal binding site was shown to contain at
      least two histidine residues in a cluster, and the presence of aspartic and
      glutamic acid as well as cysteine residues could not be excluded. Thus, simple
      competition studies allows us to obtain some partial information on the metal
      binding structural features of this anti-metal chelate antibody and to guide our
      screening of its catalytic potential.

PMID- 7578357
TI  - Synthesis and physicochemical properties of protein conjugates with water-soluble
      poly(alkylene oxides).
AB  - Conjugates of proteins (bovine serum albumin (BSA) and alpha-chymotrypsin (CHT)
      with poly(ethylene glycol) and amphiphilic block copolymers of ethylene oxide and
      propylene oxide (proxanols) were synthesized, using monoaldehyde polymer
      derivatives as the amino group modifying reagents. Four types of conjugates
      varying in the placement of hydrophobic block and type of polymer chain
      distribution were obtained. Methods of purification and characterization of
      proteins conjugated with proxanols were developed. It was shown that conjugates
      based on CHT retain high enzymatic activity toward both substrates investigated-
      N-benzoyl-L-tyrosine and casein-up to high degrees of modification (11 polymer
      chains per protein molecule). At the same time, CHT--proxanol conjugates were
      characterized by higher thermostability, the stabilizing effect increasing in
      parallel with the degree of modification. It was shown that the alteration of
      sedimentation coefficients of proteins caused by modification was negligible. On
      the basis of data obtained by the methods of hydrophobic chromatography,
      sedimentation, and differential scanning calorimetry, conformational models of
      protein-proxanol conjugates were suggested. It was supposed that conjugates form
      compact structures in aqueous solutions, which resemble intramolecular micelles,
      stabilized by hydrophobic interactions between poly(propylene oxide) blocks of
      proxanols.

PMID- 7578359
TI  - Tethered benzophenone reagents for the synthesis of photoactivatable ligands.
AB  - A new radiolabeled, bifunctional photoaffinity cross-linking reagent, N
      succinimidyl p-benzoyl-[2,3-3H2]dihydrocinnamate, has been synthesized in high
      yield and with high specific activity. This reagent can be used to append the
      benzophenone photophore to amino groups of small molecules, such as O
      aminoalkylinositol polyphosphates and polypeptides. The resulting tritiated
      photoaffinity labels can be purified and manipulated in ambient light and can be
      activated at 360 nm.

PMID- 7578358
TI  - Poly(ethylene glycol)-doxorubicin conjugates containing beta-lactamase-sensitive
      linkers.
AB  - 7-Aminocephalosporin doxorubicin (AC-Dox) was condensed with
      monomethoxypoly(ethylene glycol)-propionic acid N-hydroxysuccinimide ester (5
      kDa) or with a branched form of poly(ethylene glycol)-propionic acid N
      hydroxysuccinimide ester (10 kDa), forming M-PEG-AC-Dox and B-PEG-AC-Dox,
      respectively. These polymer drug derivatives were designed such that doxorubicin
      would be released upon Enterobacter cloacae beta-lactamase (bL)-catalyzed
      hydrolysis. Both M-PEG-AC-Dox (IC50 = 80 microM) and B-PEG-AC-Dox (IC50 = 8
      microM) were less toxic to H2981 human lung adenocarcinoma cells than doxorubicin
      (IC50 = 0.1-0.2 microM) and could be activated in an immunologically specific
      manner by L6-bL, a monoclonal antibody-bL conjugate that bound to H2981 cell
      surface antigens. In addition, the polymers were relatively stable in mouse
      plasma (< 26% hydrolysis after 24 h at 37 degrees C) and were less toxic to mice
      (maximum tolerated dose > 52 mumol/kg) than doxorubicin (maximum tolerated dose =
      13.8 mumol/kg). Pharmacokientic studies were performed in mice bearing
      subcutaneous 3677 melanoma tumors. B-PEG-AC-Dox cleared from the blood more
      slowly than M-PEG-AC-Dox and was retained to a 2.1-fold greater extent in human
      3677 melanoma tumor xenografts over a 4 h period. The intratumoral concentrations
      of both polymers far exceeded that of doxorubicin. Thus, the PEG-AC-Dox polymers
      offer the possibility of generating large intratumoral doxorubicin concentrations
      owing to their reduced toxicities, the amounts that accumulate in tumors, and the
      fact that doxorubicin is released upon beta-lactam ring hydrolysis.

PMID- 7578361
TI  - Photoimmobilization of a bioactive laminin fragment and pattern-guided selective
      neuronal cell attachment.
AB  - To attain light-dependent functionalization of biocompatible materials, a
      photolabel-derivatized, bioactive laminin fragment has been synthesized,
      chemically characterized, and photoimmobilized. Covalent high-resolution
      patterning of the laminin fragment CDPGYIGSR to hydroxylated fluorinated ethylene
      propylene (FEP-OH), poly(vinyl alcohol), and glycophase glass has been achieved.
      The synthetic peptide CDPGYIGSR was thermochemically coupled to either N-[m-[3
      (trifluoromethyl)-diazirin-3-yl]phenyl]-4-maleimidobuty ramide or 4
      maleimidobenzophenone. Photolabel-derivatized peptides were radiolabeled, and 20
      and 300 microns-sized patterns were visualized by autoradiography. The
      biospecific interaction of photoimmobilized laminin fragments with cells was
      investigated by analyzing the selective attachment of NG 108-15 neuroblastoma x
      glioma cells which bear CDPGYIGSR-specific cell surface receptors. On
      photopatterned FEP-OH membranes NG 108-15 cells differentiated in serum
      supplemented media within 1 day. Specific attachment to the immobilized
      oligopeptide CDPGYIGSR was assessed in serum-free media with competitive binding
      studies, showing an 82% decrease in cell adherence after the cell receptors were
      blocked with soluble CDPGYIGSR.

PMID- 7578360
TI  - Glycosylated polylysine/DNA complexes: gene transfer efficiency in relation with
      the size and the sugar substitution level of glycosylated polylysines and with
      the plasmid size.
AB  - A DNA delivery system based on the use of polylysine substituted with small
      recognition signals, such as carbohydrate moieties specifically recognized by
      membrane lectins present in a given cell line, has been developed [Midoux et al.
      (1993) Nucleic Acids Res. 21, 871-878]. Human hepatoma (HepG2) cells which
      express a galactose-specific membrane lectin are efficiently transfected in the
      presence of chloroquine with pSV2Luc plasmid complexed with a lactosylated
      polylysine. The optimization of the parameters involved in the formation of
      DNA/glycosylated polylysine complexes leads to the following conclusions: a high
      gene transfer efficiency is reached when (i) DNA/glycosylated polylysine
      complexes are completely retarded when subjected to electrophoresis and when (ii)
      31 +/- 4% or 40 +/- 8% of the amino groups of a polylysine having a degree of
      polymerization (DP) of 190 are substituted with lactosyl or beta-D-galactosyl
      residues, respectively. In addition, carbohydrate residues bound to polylysine
      decrease the electrostatic strength between plasmid DNA and glycosylated
      polylysine, suggesting that the strength of the electrostatic interactions
      between the plasmid and the glycosylated polylysine plays an important role in
      the efficiency of the gene expression. The optimal lactosylated polylysine
      conjugate (polylysine DP 190 substituted with 60 lactosyl residues) transfers a 5
      kb and a 12 kb plasmid with a similar efficiency.

PMID- 7578362
TI  - Oligodeoxyribonucleotides with conjugated dihydropyrroloindole oligopeptides:
      preparation and hybridization properties.
AB  - Synthesis of a new class of conjugates between oligodeoxyribonucleotides (ODNs)
      and minor groove binders (MGBs) is described. The MGBs are analogs of the potent
      antibiotic CC-1065 and consist of repeating 1,2-dihydro-3H-pyrrolo[3,2-e]indole-7
      carboxylate (DPI) subunits with N-3 carbamoyl or tert-butyloxycarbonyl groups
      (CDPI or BocDPI subunits, respectively). The ODN-MGB conjugates were obtained by
      postsynthetic modification of 5'- or 3'-amino-tailed ODNs with the 2,3,5,6
      tetrafluorophenyl (TFP) esters of CDPI1-3 or BocDPI1-2 or by ODN synthesis using
      a CDPI3-modified controlled pore glass (CPG) support. The hybridization
      properties of MGB-tailed octathymidylates were determined; they varied with
      respect to the site of conjugation (3' or 5'), the nature of the linker, the
      length of the DPI oligopeptide, and the type of N-3 substitution. Optical melting
      studies showed that the linkage of CDPI1-3 residues to (dTp)8 significantly
      increased the stability of hybrids formed by the latter with poly(dA). The extent
      of stabilization increased with the length of the peptide. When CDPI3 was
      conjugated to either end of (dTp)8, the melting temperature (Tm) of the hybrid
      formed with poly(dA) was increased by 43-44 degrees C. Free CDPI3 stabilized the
      (dTp)8-poly(dA) hybrid by only 2 degrees C, thus demonstrating the importance of
      conjugation. (dTp)8-CDPI1-3 conjugates also formed stabilized duplexes with
      poly(rA). The extent of stabilization was half that observed with poly(dA).

PMID- 7578363
TI  - Improved cytotoxicity of antitumor compounds deliverable by the LDL pathway.
AB  - The concept of LDL-based chemotherapy of cancer is based on the fact that many
      tumors have high LDL requirements. A series of compounds has been synthesized,
      some of which meet all criteria for such therapy, i.e., they can be reconstituted
      with LDL, they do not leak out of the reconstituted LDL (rLDL), and they are
      potent enough to kill cells exclusively via the LDL receptor pathway. Two of
      these compounds are significantly superior to the best one from our earlier study
      [Firestone et al. (1984) J. Med. Chem. 27, 1037-1043], being cytotoxic in rLDL at
      concentrations reasonably attainable in vivo.

PMID- 7578366
TI  - Vitamin B12 mediated oral delivery systems for granulocyte-colony stimulating
      factor and erythropoietin.
AB  - As a prelude to the development of orally active erythropoietin (EPO) and
      granulocyte-colony stimulating factor (G-CSF), conjugates have been formed
      between these molecules and vitamin B12. During the formation of these conjugates
      intramolecular cross-linking of the proteins was avoided by the use of hydrazidyl
      derivatives of vitamin B12. A potentially biodegradable linkage was formed
      between vitamin B12 and G-CSF by reaction of the buried thiol in G-CSF with a
      long chain dithiopyridyl derivative of vitamin B12. In vitro and in vivo testing
      of the conjugates showed that their bioactivity was substantially maintained and
      that they were actively transported in an intrinsic factor dependent fashion
      across CaCo-2 cells and from the intestine to the circulation in a biologically
      active form.

PMID- 7578367
TI  - Preparation and nuclease activity of hybrid
      "metallotris(methylpyridinium)porphyrin oligonucleotide" molecules having a 3'
      loop for protection against 3'-exonucleases.
AB  - A 5'-GCGAAAGC minihairpin structure was added to the 3'-end of an oligonucleotide
      substituted at the 5'-end by a manganese cationic porphyrin in order to enhance
      the 3'-exonuclease resistance of these cleaver-antisense molecules. The influence
      of this minihairpin on the 3'-exonuclease resistance, the binding affinity to a
      target ssDNA, and the cleaving efficiency of Mn-cationic porphyrin
      oligonucleotide conjugates was compared to that of the parent molecule without
      the 3'-hairpin. The results showed that the 3'-hairpin slightly decreased the
      binding affinity and consequently the cleaving efficiency of the conjugated
      molecule toward a target sequence, but the much higher nuclease resistance makes
      3'-minihairpin-protected metalloporphyrin oligonucleotides good candidates as
      reactive antisense oligonucleotides for studies on cells.

PMID- 7578365
TI  - Comparison of three common amine reactive fluorescent probes used for conjugation
      to biomolecules by capillary zone electrophoresis.
AB  - The conjugation of three amine reactive fluorescent probes, each containing the
      fluorophore fluorescein but different reactive moieties, was compared using the
      protein myoglobin and the amino acid L-lysine as reagents. The three different
      reactive moieties were an isothiocyanate group (FITC), a succinimidyl ester group
      (CFSE), and a dichlorotriazine group (DTAF). The relative performance was based
      on the degree of conjugation to myoglobin, the rate of reaction, freedom from
      hydrolysis, and the stability of a conjugate with lysine. Performance was
      evaluated by separating the conjugation reaction reagents and products on-line,
      using capillary zone electrophoresis, and assessing relative amounts by
      absorbance detection. Each of the reactive probes demonstrated the ability to
      achieve a similar degree of conjugation, which depended mostly on allowed
      conjugated reaction time, and a rate of conjugation that rendered hydrolysis of
      the reactive moiety insignificant. For the relative rate of conjugation between
      probes and stability of the resulting conjugate, CFSE demonstrated superior
      performance, followed by DTAF and then FITC, for both the protein myoglobin and
      the amino acid L-lysine. The FITC conjugation reaction was much easier to
      control, however, which may be significant for applications that require a
      precise degree of conjugation. With regard to conjugate-bond stability, the FITC
      conjugate demonstrated inferior performance when subjected to incubation at 37
      degrees C.

PMID- 7578368
TI  - Synthesis of novel phosphoramidite reagents for the attachment of antisense
      oligonucleotides to various regions of the benzophenanthridine ring system.
AB  - Four benzophenanthridine phosphoramidite reagents have been prepared in which the
      linker chain between the benzophenanthridine and the phosphoramidite moiety is
      attached to C-2, C-6, C-9, and C-12 of the benzophenanthridine ring system. These
      benzophenanthridine phosphoramidites should prove to be useful in the syntheses
      of antisense oligonucleotide-intercalator conjugates in which the linker chain is
      attached to various regions of the benzophenanthridine intercalator. One of the
      new benzophenanthridine phosphoramidite reagents was used to prepare an antisense
      oligonucleotide-intercalator conjugate in which the oligonucleotide TCAGTGGTp was
      connected at its 5'-hydroxyl group through a linker chain to the C-2 hydroxyl
      group of a benzophenanthridine.

PMID- 7578364
TI  - Site-specific prodrug activation by antibody-beta-lactamase conjugates:
      preclinical investigation of the efficacy and toxicity of doxorubicin delivered
      by antibody directed catalysis.
AB  - Antibody directed catalysis (ADC), the catalytic conversion of prodrugs to drugs
      by enzymes localized at disease targets by appropriate monoclonal antibodies, has
      shown promise in the treatment of cancer in nude mouse xenograft models. We
      investigated this concept using antibody enzyme conjugates constructed from beta
      lactamase and Fab's reactive with carcinoembryonic antigen, CEA, and tumor
      associated glycoprotein, TAG-72, to convert prodrugs that are cephalosporin
      sulfoxide derivatives into oncolytic drugs. Previous work focused on ADC delivery
      of the potent vinca alkaloid derivative desacetylvinblastine carboxhydrazide
      (DAVLBHYD). In the current study the ability of the system to deliver doxorubicin
      was tested in MCF7 breast carcinoma xenografts and OVCAR3 ovarian carcinoma
      xenografts, and in T380 and LS174T colon tumor xenografts for comparison with
      previous DAVLBHYD results. ADC enhanced the delivery of doxorubicin in the model
      systems investigated. Tumor growth suppression was equivalent to or greater than
      that observed with free doxorubicin at its maximum tolerated dose (MTD). In
      contrast to the DAVLBHYD results, ADC delivery of doxorubicin did not regress
      tumors, but did result in a substantial increase in the MTD.

PMID- 7578372
TI  - Bibliography of the current world literature: Supportive care.

PMID- 7578373
TI  - Bibliography of world literature: Sarcomas.

PMID- 7578374
TI  - Bibliography of world literature: Gastrointestinal tract.

PMID- 7578370
TI  - Catabolism of radioiodinated murine monoclonal antibody F(ab')2 fragment labeled
      using N-succinimidyl 3-iodobenzoate and Iodogen methods.
AB  - The F(ab')2 fragment of monoclonal antibody (MAb) Me1-14 was labeled with 125I
      using the Iodogen method and by reaction with N-succinimidyl 3-[125I]iodobenzoate
      (SIB). The labeled catabolites generated after exposure to tissue homogenates in
      vitro and following administration of labeled F(ab')2 into normal mice were
      investigated by size-exclusion HPLC, gel electrophoresis, and reverse-phase HPLC.
      Rapid conversion of F(ab')2 to Fab was observed with both labeling methods. With
      F(ab')2 labeled using the Iodogen method, the primary low molecular weight
      catabolites appeared to be [125I]iodide and, to a lesser extent,
      mono[125I]iodotyrosine. With SIB, [125I]iodide and [125I]iodobenzoic acid (IBA)
      as well as the glycine and lysine conjugates of IBA were all observed.
      Differences in low molecular weight catabolic products could explain the more
      rapid normal tissue clearance with MAbs and MAb fragments labeled with SIB
      compared with those labeled using iodogen.

PMID- 7578375
TI  - Supportive care: what for?

PMID- 7578369
TI  - Enantioselective release of 5-fluorouracil from N-(2-hydroxypropyl)methacrylamide
      based copolymers via lysosomal enzymes.
AB  - Water soluble copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA)
      containing oligopeptide side chains terminated in an alpha-substituted glycine
      derivative of the anticancer compound 5-fluorouracil (5-FU) were synthesized by a
      new facilitated synthetic route and studied for their ability to release free 5
      FU in the presence of lysosomal enzyme preparations. In addition, the properties
      of the low molecular weight alpha-substituted glycine derivatives were studied in
      the presence of lysosomal enzyme preparations and leucine aminopeptidase. The
      results revealed that (1) the stereochemistry (L vs D) of the alpha-substituted
      glycine derivative, (2) the hydrophobicity (Ala vs Leu) of the penultimate amino
      acid residue relative to the alpha-substituted glycine derivative, and (3) the
      total length of the oligopeptide sequence spacer (tetrapeptide vs hexapeptide)
      terminated in the alpha-substituted glycine derivative and the polymer carrier
      all directly influence the enzymatically catalyzed release of free 5-FU.

PMID- 7578371
TI  - Quantitation of triple-helix formation using a photo-cross-linkable aryl
      azide/biotin/oligonucleotide conjugate.
AB  - DNA triple-helix formation has potential applications in gene mapping and as the
      basis of "antigene" pharmaceuticals; however, the methods for quantitation of
      triple-helix formation are limited, especially for purine(purine-pyrimidine)
      based triplexes. We present a novel method for detection and quantitation of
      triple-helix formation by triple-helix-forming oligonucleotides. The
      oligonucleotide is conjugated to a photoactivatable cross-linker,
      sulfosuccinimidyl 3-[[2-[6-(biotinamido)-2-(p-azidobenzamido)hexanamido]
      ethyl]dithio] propionate. After incubation with the target DNA, exposure to light
      labels the target with biotin. The labeled target can be quantified by a
      chemiluminescent assay. A 26-mer oligonucleotide previously reported to form a
      purine(purine-pyrimidine) triplex with the upstream region of the c-myc gene was
      studied and found to bind to its target with Kd of approximately 100 nM at 37
      degrees C, 10 mM MgCl2, pH 7.5, consistent with previous reports. This new
      technique can be used under a variety of conditions and in kinetic experiments
      and may be extendible to use in living cells.

PMID- 7578376
TI  - Cardiotoxicity and cardioprotection during chemotherapy.
AB  - Chemotherapy drugs have been reported to cause cardiac side effects including
      cardiomyopathy, ischemia, arrhythmias, and myocardial necrosis. Most important in
      terms of daily practice is anthracycline-induced cardiomyopathy. The
      bisdioxopiperazine compound, dexrazoxane (ICRF-187, ADR-529), has been shown to
      prevent this cumulative side effect of the anthracyclines. Recent randomized
      trials performed in breast cancer and in pediatric sarcoma patients have
      demonstrated the efficacy of this approach, which permits the administration of
      anthracyclines to greater cumulative doses and thus leads to a substantial
      reduction in the incidence of decreased left-ventricular ejection fraction or
      congestive heart failure. Response rates were not significantly different with
      the use of dexrazoxane in these trials. The risk ratio for a cardiac event was
      decreased by two to threefold in randomized breast studies involving more than
      700 women. Paclitaxel also has been reported to cause arrhythmias and possibly
      ischemia. In a large data base, National Cancer Institute investigators found a
      0.29% incidence of grade 4 or 5 cardiac toxicities, including heart block,
      ventricular tachycardia, and ischemic events. Other important chemotherapy
      related cardiac toxicities discussed include fluorouracil-induced angina and
      arrhythmias, interleukin-4 induced-cardiomyopathy, and cardiotoxicity associated
      with autologous bone marrow transplantation procedures.

PMID- 7578377
TI  - Strategies to prevent nephrotoxicity of anticancer drugs.
AB  - Nephrotoxicity is a relatively common and potentially serious adverse effect of
      treatment with certain cytotoxic drugs (especially ifosfamide). The patient may
      develop severe chronic proximal tubular toxicity. It is therefore very important
      to attempt to reduce the frequency and severity of acute and chronic
      nephrotoxicity resulting from chemotherapy. A logical approach is described, with
      particular reference to ifosfamide and cisplatin, involving improved evaluation
      of the important clinical features of nephrotoxicity and a greater understanding
      of its pathogenesis. This approach will facilitate the development of logical
      preventive strategies, or less toxic analogues, or both. The methods used may
      also enable prediction of the potential nephrotoxicity of newly developed
      cytotoxic agents.

PMID- 7578379
TI  - Oral complications of local and systemic cancer treatment.
AB  - Acute and chronic complications of oral tissues and changes in physiologic
      process frequently accompany cancer therapies. Mucositis is a common dose
      limiting complication in patients receiving systemic cancer chemotherapy, bone
      marrow transplantation, and local irradiation for tumors in the head and neck
      area. In addition, mucosal ulcerations may become portals for the invasion of
      pathogens that in turn may be life threatening. Oral environment changes and
      salivary gland dysfunction cause an increase in dental caries and periodontal
      disease in dentulous patients who receive radiation therapy in and around the
      oral cavity. Some of these therapy-related oral complications can be controlled
      by pretherapy modification of the oral environment, such as elimination of acute
      and potential dental and periodontal foci of pathoses, patient participation in
      oral care, and awareness by dentists and oncologists that cancer patients require
      specific oral care. Prevention and management of oral mucositis, as well as
      prevention and control of dental pathoses, are still problems that need further
      investigation.

PMID- 7578378
TI  - Management of chemotherapy-induced anemia.
AB  - Chronic anemia associated with cancer often causes poor quality of life and is
      often exacerbated by intensive treatment. In recent controlled trials,
      recombinant human erythropoietin (rhEpo) proved to be well tolerated and
      effective in amelioration and reduction of transfusion requirements of cancer
      associated anemia. Double-blind placebo-controlled trials of rhEpo in patients
      undergoing allogenic, but not autologous, bone marrow transplantation showed
      significant acceleration of the reconstitution of erythropoiesis. Multivariate
      analysis revealed that serum erythropoietin levels of 100 mU/mL or greater and an
      increase in hemoglobin by at least 0.5 g/dL was a probable response; conversely,
      a serum ferritin level of 400 ng/mL or greater after 2 weeks indicated a poor
      response to rhEpo therapy. Further studies are needed to define patient
      populations in whom cost-effective rhEpo therapy is justified.

PMID- 7578380
TI  - Management of diarrhea induced by tumors or cancer therapy.
AB  - Diarrhea is a common event in the clinical history of cancer patients. It can be
      caused by the presence of tumor or it can be a side effect of treatment. The
      latter problem is occurring more often because new drugs (CPT-11) or drug
      combinations (fluorouracil plus interferon or leucovorin) have diarrhea as the
      dose-limiting toxicity. The clinical use of octreotide, a long-acting
      somatostatin analogue, seemed to demonstrate an improvement in most diarrheal
      states induced by tumors (endocrine tumors) or by treatments (short bowel
      syndrome; chemotherapy-induced diarrhea).

PMID- 7578382
TI  - Diagnosis and treatment of soft tissue sarcomas in adults.
AB  - The optimal treatment of soft tissue sarcoma remains a challenge for the
      multidisciplinary approach in modern oncology. Only when a team of experienced
      clinicians, oncologists, radiotherapists, and oncologic orthopedic surgeons
      cooperates with the radiologist and the pathologist can optimal treatment be
      guaranteed. Recent advances in our knowledge of sarcomas have resulted from more
      detailed analysis of the cytogenetic and molecular changes in the different types
      of sarcoma. The prognostic significance of many biologic markers is still the
      subject of ongoing investigations, with sometimes conflicting results. The
      usefulness of adjuvant radiotherapy in the combined approach for optimal local
      control of both extremity and trunk sarcomas is confirmed in different studies.
      the discovery of antitumor activity of taxoids in this disease brings new
      chemotherapeutic combinations within reach.

PMID- 7578381
TI  - Cytogenetics and experimental models of sarcomas.
AB  - Bone and soft tissue sarcomas are diagnostically challenging. Recognition of
      specific cytogenetic abnormalities in these neoplasms has significantly reduced
      some of the associated difficulties and has provided valuable information on
      histopathogenesis. Commonly, translocations involving an exchange of chromosomal
      material and creation of novel chimeric genes are detected. These fusion genes
      frequently function as aberrant transcription factors that contribute to
      sarcomagenesis. New studies indicate that less commonly occurring variant fusion
      genes are also present in some tumors, eg, Ewing's sarcoma and alveolar
      rhabdomyosarcoma. The clinical consequences, if any, of these variant hybrids are
      not yet known. Reverse transcriptase polymerase chain reaction and are useful
      approaches in detecting these transcripts. In addition to translocations,
      supernumerary ring chromosomes are often encountered in sarcomas, particularly
      those of intermediate or borderline malignancy. Traditional fluorescence in situ
      hybridization, and recently, comparative genomic hybridization have uncovered the
      chromosomal composition of these rings as well as some associated gene
      amplifications in well-differentiated liposarcoma and dermatofibrosarcoma
      protuberans.

PMID- 7578384
TI  - Ewing's sarcoma and extracranial peripheral neuroectodermal tumors.
AB  - Ewing's sarcoma and extracranial primitive neuroectodermal tumors of bone and
      soft tissue are small round-cell tumors that comprise a family of neoplasms
      distinguished by a cytogenetic marker that can be detected by reverse
      transcription and polymerase chain reaction. Based on molecular and
      immunohistochemical studies, it is generally acknowledged that this is a family
      of neuroectodermal tumors. Molecular methods allow accurate diagnosis with
      minimally invasive surgical options, provide a manner to detect minimal residual
      disease, and begin to shed light on the pathogenesis of these entities. Combined
      modality treatment regimens continue to improve the outlook for nonmetastatic
      Ewing's sarcoma and primitive neuroectodermal tumors patients. Patients who
      present with metastatic disease may benefit from intensive therapy as facilitated
      by peripheral stem cell and autologous bone marrow rescue programs.

PMID- 7578383
TI  - Osteosarcoma and other tumors of bone.
AB  - Although no major advances in local or systemic therapy have been reported,
      further progress has been made in the identification of genetic alterations and
      prognostic factors in primary as well as recurrent osteosarcoma. Further reports
      on the use of a variety of imaging techniques in the quantification of tumor
      response to neoadjuvant chemotherapy have also appeared. Publications describing
      high-dose methotrexate pharmacokinetics, the impact of this therapy on patient
      outcome, and a report of a pilot study evaluating the feasibility of higher dose
      intensity cisplatin and doxorubicin may lead to new and important randomized
      clinical trials in the future.

PMID- 7578385
TI  - Rhabdomyosarcoma and other soft tissue sarcomas of childhood.
AB  - This review of the past year's literature summarizes the most relevant advances
      in the biology and therapy of rhabdomyosarcoma and other pediatric soft tissue
      sarcomas. The results of the third Intergroup Rhabdomyosarcoma Study clearly show
      that therapy based on specific risk factors offers the best chance of cure for
      children with rhabdomyosarcoma. The recent identification of nonrandom
      chromosomal translocations within distinct histologic subtypes of
      rhabdomyosarcoma and nonrhabdomyosarcoma soft tissue sarcomas offers a unique
      opportunity to improve our ability to diagnose, stage, and monitor these
      patients. Finally, identification of the genetic features that characterize these
      tumors will help us better understand the mechanisms involved in tumorigenesis
      and will facilitate the development of novel specific therapies.

PMID- 7578386
TI  - Interventional radiology in gastrointestinal neoplasms.
AB  - Interventional radiology plays a significant role in different fields of
      gastrointestinal oncology. Percutaneous techniques can be used to diagnose and
      stage bile duct and pancreatic cancer. Palliation of esophageal tumors and
      malignant biliary obstruction may be achieved with interventional techniques,
      whereas curative attempts are directed mainly towards primary and secondary liver
      tumors. The therapeutic potential of interventional radiology is still expanding,
      as are all other forms of minimally invasive therapy. This article reviews the
      relevant contributions on this subject that have appeared in the past year. The
      introduction of new techniques is described, and the results of clinical studies
      are discussed.

PMID- 7578387
TI  - Screening for gastrointestinal cancer.
AB  - No new sound evidence pointing to the effectiveness of screening for any
      gastrointestinal cancer has become available in the past year. Although
      recommended in Japan, screening for gastric cancer is expensive, and in a study
      in Venezuela it was found to be ineffective. The sensitivity of the standard
      hemoccult test for fecal occult blood is low; variants have improved sensitivity
      but relatively poor specificity remains. A major review of the evidence on
      colorectal cancer screening concluded that it was not recommended as part of the
      periodic health examination. Colorectal cancer mortality is falling in North
      America, possibly due to prevention (dietary modification) rather than screening.
      As dietary modification has benefits on other cancers and diseases, it is
      preferable as a colorectal cancer control strategy. Screening for other
      gastrointestinal cancers cannot be recommended.

PMID- 7578388
TI  - The role of dietary factors and chemoprevention in gastrointestinal malignancy.
AB  - Environmental factors, particularly pertaining to the diet, are of importance in
      the pathogenesis of gastrointestinal neoplasia. Increasingly sophisticated
      studies have begun to elucidate some of the mechanisms responsible for both the
      deleterious and protective effects of compounds ingested or smoked (such as
      tobacco). The new and developing field of chemoprevention holds great promise for
      the possibility of averting neoplasia by interfering with the metabolism of
      carcinogens, reducing their binding to the target cell, or even by suppressing
      the initiated cell.

PMID- 7578389
TI  - Esophageal cancer.
AB  - Esophageal cancer is a disease of the developing nations worldwide, and it is
      associated with nutritional deficiencies and exposure to tobacco and alcohol. In
      the West, the epidemiology is changing with an unexplained increase in
      adenocarcinoma of the distal esophagus and gastroesophageal junction, whereas
      rates for squamous cell carcinoma remain stable. Advances in our understanding of
      the epidemiology and molecular biology of this disease are being translated into
      clinical applications in screening and prognosis. Combined-modality therapy with
      chemotherapy, radiation therapy, and surgery appears promising for improving long
      term and disease-free survival. The optimum combinations of modalities and best
      surgical procedures await to be defined in controlled clinical trials. This
      article uses the recent literature to illustrate our evolving knowledge of the
      basic biology and clinical management of esophageal cancer.

PMID- 7578390
TI  - Primary liver cancers.
AB  - A review of the recent literature about liver cancers shows the increasing role
      of hepatitis C as a risk factor for the development of hepatocellular carcinoma.
      A new discussion has arisen with regard to the association between the use of
      oral contraceptives and hepatocellular carcinoma. Patients at risk for developing
      liver cancer can be identified and should undergo thorough follow-up to detect
      cancer at an early stage. Surgical resection remains the treatment of choice
      whenever feasible. Because of disappointing results and limited availability of
      donor organs, liver transplantation must be considered only in selected patients
      with unresectable tumors. There are also arguments recommending transplantation
      in early resectable hepatocellular carcinoma in patients with cirrhosis to cure
      the underlying cancer-bearing disease. Improvement of survival can be expected by
      promising multimodality treatment protocols that have been started during the
      past few years. Further studies should also investigate the role of
      immunosuppression in the treatment of tumor recurrence. For patients excluded
      from resection and transplantation, the most effective treatment options are
      transarterial chemoembolization and, in small lesions, percutaneous ethanol
      injection therapy. In small tumors, combination therapy seems to be even more
      appropriate.

PMID- 7578391
TI  - Preclinical pharmacokinetics, manufacturing, and safety studies supporting a
      multicenter cancer gene therapy trial.

PMID- 7578392
TI  - Assessing risk.

PMID- 7578393
TI  - Cancer gene therapy using plasmid DNA: pharmacokinetic study of DNA following
      injection in mice.
AB  - The fate of plasmid DNA complexed with cationic lipids delivered intravenously in
      mice was evaluated at selected timepoints up to 6 months postinjection. Blood
      half-life and tissue distribution of plasmid DNA and potential expression in
      tissues were examined. Southern blot analyses of blood indicated that intact
      plasmid DNA was rapidly degraded, with a half-life of less than 5 min for intact
      plasmid, and was no longer detectable at 1 hr postinjection. Southern analyses of
      tissue demonstrated that intact DNA was differentially retained in the lung,
      spleen, liver, heart, kidney, marrow, and muscle up to 24 hr postinjection. After
      7 days, no intact plasmid DNA was detectable by Southern blot analysis; however,
      the plasmid was detectable by the polymerase chain reaction (PCR) in all tissues
      examined at 7 and 28 days postinjection. At 6 months postinjection, femtogram
      levels of plasmid were detected only in muscle. Immunohistochemical analyses did
      not detect encoded protein in the tissues harboring residual plasmid at 1 or 7
      days postinjection.

PMID- 7578394
TI  - Cancer gene therapy using plasmid DNA: purification of DNA for human clinical
      trials.
AB  - A production method has been developed for the purification of pharmaceutical
      grade plasmid DNA for in vivo gene therapy. This method has been applied to the
      purification of VCL-1005, which is a eukaryotic plasmid expression vector that
      codes for the production of the HLA-B7 protein. Purified VCL-1005 is formulated
      with a cationic lipid and injected directly into established tumors of HLA-B7
      negative patients with advanced cancers to heighten the patient's immune response
      against the cancer. The purification of pharmaceutical-grade plasmid DNA requires
      the development of highly reproducible and scaleable processing methods that meet
      regulatory standards similar to those required for the manufacture of recombinant
      protein pharmaceuticals. Defined pharmaceutical standards of purity, potency,
      efficacy, and safety are routinely met by the process described in this study.
      The scaleable purification method described here is a combination of highly
      reproducible unit operations; alkaline lysis, precipitation, and size-exclusion
      chromatography. The advantages over existing DNA purification methods include
      improved plasmid purity and the elimination of undesirable process additives such
      as toxic organic extractants and animal-derived enzymes. The overall process
      yield of purified plasmid DNA from fermentation through final column purified
      product is greater than 50%. Contaminating Escherichia coli DNA levels are
      reproducibly below 1% as measured by Southern analysis. Endotoxin levels are less
      than 0.03 endotoxin units/micrograms plasmid DNA and residual protein is
      undetectable. This process was used to produce 100 mg of VCL-1005 for use in an
      active clinical protocol.

PMID- 7578395
TI  - Cancer gene therapy using plasmid DNA: safety evaluation in rodents and non-human
      primates.
AB  - To evaluate the safety of a plasmid DNA-lipid complex, a series of good
      laboratory practice (GLP) safety studies were conducted with VCL-1005, a plasmid
      DNA expression vector containing both the human class I MHC HLA-B7 heavy-chain
      and the beta 2-microglobulin (beta 2m) light-chain genes formulated with the
      cationic lipid, DMRIE/DOPE. In mice, the repeated intravenous injection of VCL
      1005 at plasmid DNA doses of 0.1, 1.0, or 10 micrograms for 14 days had only
      incidental effects on clinical chemistry and hematology, and did not result in
      any organ pathology. Repeated intrahepatic injections of VCL-1005 in mice did not
      result in significant liver histopathology or significant alterations in liver
      enzymes. In cynomolgus monkeys, the repeated intravenous administration of VCL
      1005 at a cumulative dose of 720 micrograms of DNA had no effects on clinical
      chemistry, hematology, or organ pathology. Thus, systemic administration of a
      plasmid DNA expression vector containing the coding sequence for a foreign MHC
      class I molecule did not result in significant toxicity or a pathological immune
      response in animals. These results suggest that the direct transfer of VCL-1005,
      a plasmid DNA-lipid complex, could be used for the safe in vivo delivery of
      recombinant DNA for a cancer gene therapy trial.

PMID- 7578396
TI  - Cytokine gene therapy with interleukin-2-transduced fibroblasts: effects of IL-2
      dose on anti-tumor immunity.
AB  - We evaluated the effects of different doses of interleukin-2 (IL-2)-transduced
      fibroblasts in the treatment of colorectal carcinoma in the CT-26 murine tumor
      model. Immunization with a mixture of irradiated tumor cells and IL-2-transduced
      fibroblasts (100 units of IL-2/24 hr) induced significantly greater protection
      against a live tumor challenge compared to irradiated tumor cells alone (22/35,
      65% vs. 10/30, 33%, p < 0.02). Protective effects were observed with doses of IL
      2-transduced fibroblasts secreting from 5 to 100 units of IL-2/24 hr. Parallel
      experiments in nude mice produced no protection, indicating that the effects of
      immunization were mediated by a T-cell-dependent mechanism. In animals with
      established tumors, complete tumor remissions were observed following
      immunization with a mixture of irradiated tumor cells and IL-2-transduced
      fibroblasts secreting 100 units of IL-2/24 hr, but not after immunization with
      irradiated tumor cells alone (7/16 vs. 0/11 complete remissions, p < 0.02).
      Fibroblasts secreting higher doses of IL-2 were ineffective in generating
      systemic immunity, but were required to prevent tumor implantation. A
      statistically significant difference in the prevention of tumor implantation was
      observed between groups inoculated with a mixture of live tumor cells and IL-2
      transduced fibroblasts (1,750 units of IL-2/24 hr) compared to control
      fibroblasts (6/8 vs. 0/12, p < 0.001). Similar results were observed in nude
      mice, suggesting that the implantation rejection response is mediated in part by
      cells other than thymus-derived T cells. Our data support the utility of IL-2
      transduced fibroblasts and indicate that the level of IL-2 expression is an
      important variable in activating different effector components of antitumor
      immune responses in IL-2 gene therapy.

PMID- 7578397
TI  - Gene transfer to synovial cells by intra-articular administration of plasmid DNA.
AB  - We studied reporter gene expression in synovial tissue after intra-articular
      administration of an expression plasmid into the knees of rabbits and rats. In
      both species, administration of a plasmid encoding beta-galactosidase led to gene
      expression in the synovial cells lining the joint. Expression correlated with the
      presence of plasmid DNA in synovial tissue extracts. Studies with a plasmid
      encoding chloramphenicol acetyltransferase demonstrated that gene expression
      persists for 2-5 days after administration. Southern blotting demonstrated that
      the administered plasmid was taken up rapidly by synovial tissue and degraded. By
      24 hr after administration, no intact plasmid could be detected by Southern
      blotting, although small amounts of plasmid could be amplified by PCR up to 7
      days. Administration of a plasmid encoding human growth hormone demonstrated that
      this product could be expressed from synovial cells and secreted into the
      synovial fluid. The histological distribution of gene expression in synovium
      resembles the known distribution of particulate materials injected into the joint
      and suggests that plasmid DNA is taken up by nonspecific endocytosis like other
      particulate materials during the remodeling of synovial fluid.

PMID- 7578398
TI  - Retrovirus-mediated transduction of an engineered intron-containing purine
      nucleoside phosphorylase gene.
AB  - We constructed and tested several retroviral vectors containing abbreviated
      purine nucleoside phosphorylase (PNP) genes in the reverse orientation, a
      strategy compatible with transduction of intron-containing genes. We observed two
      types of deletions in these vectors after one round of replication: (i) Deletions
      flanked by direct repeats with one copy of the repeat retained in the provirus,
      presumably resulting from reverse transcriptase slippage during (-) strand DNA
      synthesis. (ii) Deletions due to fortuitous splice sites in the PNP complementary
      strand. Two splice donor sites and three splice acceptor sites were identified in
      a 3.0-kb PNP minigene. We found that the splice donor sites (but not the splice
      acceptor sites) could be predicted by sequence analysis of the PNP complementary
      strand. To increase the frequency of intact PNP gene transduction, we introduced
      sequence modifications: The putative PNP polyadenylation signal and a truncated
      117-bp 3' flank were recovered from a rearranged provirus and inserted in place
      of a 1.2-kb genomic 3' flank. Sequences associated with deletions were eliminated
      from the PNP 5' untranslated region, and two fortuitous splice donor signals in
      the complementary strand were inactivated. A retroviral vector LN-PMG11,
      containing the engineered 2.9-kb PNP minigene in the reverse orientation, was
      transduced intact in 23% (5/22) of clones after one round of replication and in
      87% (20/23) of clones after a second round of replication from two primary virus
      producer clones. Directed mutagenesis of sequences preventing intact retroviral
      transduction thus provided a 2.9-kb PNP gene that was transduced intact and
      expressed at a high level.

PMID- 7578399
TI  - RevM10-mediated inhibition of HIV-1 replication in chronically infected T cells.
AB  - Two clinical regimens have been proposed for gene therapies of acquired
      immunodeficiency syndrome (AIDS): (i) Genetic modification of differentiated
      peripheral mononuclear cells ex vivo and (ii) gene delivery into hematopoietic
      stem/progenitor cells ex vivo. Various antiviral strategies targeted at different
      molecular processes in the human immunodeficiency virus type 1 (HIV-1) life cycle
      are currently being pursued, all with the goal of reducing HIV-1 replication.
      Until now, all successful studies have reported inhibition in acutely HIV
      infected cells that had been genetically modified prior to infection. These
      promising results do not address a clinically relevant question: What is the
      contribution of already infected peripheral mononuclear and hematopoietic
      stem/progenitor cells to disease progression? In this report, we demonstrate
      inhibition of both HIV-1 replication and production of infectious particles in
      chronically infected human T leukemia cell lines. The antiviral effect on the
      transduced cell population correlates with the expression of the dominant
      negative RevM10 protein. This is the first demonstration that a gene therapy
      based treatment can achieve antiviral efficacy in human T leukemia cells
      chronically infected with HIV-1.

PMID- 7578400
TI  - The effects of human serum and cerebrospinal fluid on retroviral vectors and
      packaging cell lines.
AB  - Human serum is known to inactivate many retroviruses, including murine leukemia
      viruses (MLV). Exposure of vectors based on MLV to human serum components would
      presumably decrease the efficiency of gene transfer in vivo. Human serum also
      lyses xenogeneic cells, which would affect the survival of retroviral vector
      packaging cells in vivo. The effects of other body fluids, such as cerebrospinal
      fluid (CSF), on MLV vectors and packaging lines have not been studied. We have
      found that retroviral vectors packaged in ecotropic, amphotropic, and gibbon ape
      leukemia virus (GALV) envelope proteins were all inactivated by human sera, and
      human sera also lysed mouse NIH-3T3 cells and the retroviral vector packaging
      cells derived from them. Human fibroblasts producing amphotropic vector particles
      were resistant to lysis, but the particles produced by them were inactivated. In
      contrast, CSF did not inactivate MLV vectors, nor did it lyse murine retrovirus
      packaging cells. Our results suggest that exposure to human serum may prevent in
      vivo gene transfer by MLV vectors and xenogeneic packaging lines, but gene
      transfer within the central nervous system should be more successful.

PMID- 7578401
TI  - A phase 1 study, in cystic fibrosis patients, of the safety, toxicity, and
      biological efficacy of a single administration of a replication deficient,
      recombinant adenovirus carrying the cDNA of the normal cystic fibrosis
      transmembrane conductance regulator gene in the lung.

PMID- 7578402
TI  - Evaluation of repeat administration of a replication deficient, recombinant
      adenovirus containing the normal cystic fibrosis transmembrane conductance
      regulator cDNA to the airways of individuals with cystic fibrosis.

PMID- 7578404
TI  - Retroviral-mediated gene transfer and expression of human lipoprotein lipase in
      somatic cells.
AB  - Lipoprotein lipase (LPL) is an enzyme responsible for the hydrolysis of
      triglyceride-rich circulating lipoproteins. Humans with complete defects in LPL
      activity present from infancy with failure to thrive, eruptive xanthomas,
      pancreatitis, and lactescent plasma. In addition, heterozygous carriers for this
      disorder may be at increased risk for the development of coronary artery disease.
      In view of a potential strategy for correcting complete or partial LPL
      deficiency, a 1.56-kb human LPL cDNA was inserted into a series of recombinant
      myeloproliferative sarcoma virus (MPSV)-based retroviral vectors under
      transcriptional control of the constitutive MPSV long terminal repeat (LTR).
      Stable gene transfer and enhanced expression of human LPL was observed at both
      the RNA and protein level in a variety of somatic cell types in vitro.
      Genetically modified cell populations included mouse NIH-3T3 fibroblasts and
      C2C12 myoblasts, primary human fibroblasts, and established human hematopoietic
      cell lines of erythroid (K562), myelocytic (HL60), and monocytic (U937,THP-1)
      type. The achieved levels of bioactive human LPL were found to vary widely
      between the different transduced cell lines, which may be critical to an approach
      to gene therapy. Transduced primary human fibroblasts yielded maximal elevation
      of LPL immunoreactive mass and activity of at least 24- and 50-fold,
      respectively, above constitutively expressed levels for this cell type. Human
      fibroblasts, therefore, appear to accommodate in vitro the complex processes
      readily leading to the maturation and secretion of bioactive human LPL and may
      serve as an effective cellular vehicle for LPL gene delivery and expression in
      human LPL deficiency.

PMID- 7578405
TI  - High-efficiency retroviral gene transfer into murine high-proliferative-potential
      cells cycle-activated by cytosine arabinoside.
AB  - We investigated cytosine arabinoside (Ara-C) as a potential agent for in vivo
      cycle activation of hematopoietic progenitors for the purpose of retroviral
      mediated gene transfer. C57Bl mice were treated intraperitoneally with one of
      three regimens of Ara-C: a single 1,750 mg/kg dose (regimen 1), a 1,750 mg/kg
      dose on day 0, and a 1,500 mg/kg dose on day 2 (LD50) (regimen 2), or a 1,750
      mg/kg dose on day 0 and a 1,500 mg/kg dose on day 3 (regimen 3). The high
      proliferative-potential cells (HPPC)/10(5) cells were 47.0 +/- 7.5 pretreatment.
      The post-treatment HPPC cloning efficiencies were 40.6 +/- 3.4, 83.6 +/- 6.1, and
      20.4 +/- 3.2 HPPC/10(5) cells on days 1, 2, and 4, respectively, with regimen 1;
      60.0 +/- 7.9, 194.0 +/- 9.6, and 103.0 +/- 11.0 HPPC/10(5) cells 1, 2, and 4 days
      after the second Ara-C dose, respectively, with regimen 2; and 266 +/- 13.4, 132
      +/- 23.9, and 118.0 +/- 5.7/10(5) cells 1, 2, and 4 days after the second Ara-C
      dose, respectively, with regimen 3. The transduction efficiency of HPPC from
      untreated animals with N2 viral supernatant was 4.9 +/- 5.8%.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7578403
TI  - Transfer of the CFTR gene to the lung of nonhuman primates with E1-deleted, E2a
      defective recombinant adenoviruses: a preclinical toxicology study.
AB  - This paper describes a preclinical toxicology study designed to investigate the
      biological efficacy and safety profile of second-generation adenovirus for CFTR
      gene transfer into the baboon lung. This second-generation virus is deleted of E1
      and contains a temperature-sensitive mutation in the E2a gene, which encodes a
      defective DNA-binding protein. Two distinct projects were undertaken. Group A
      animals received a first-generation adenovirus (i.e., deleted of E1) in an upper
      lobe at the time a second-generation virus was instilled into the contralateral
      upper lobe. The goal of study A was to compare the biology of each construct
      directly and to determine if an immune response to the first-generation virus
      affected the performance of the second-generation virus. Group B animals received
      a lacZ second-generation virus in an upper lobe at the same time the CFTR second
      generation virus was instilled in the other upper lobe. Necropsies were performed
      4 or 21 days after gene transfer and tissues were evaluated for recombinant gene
      expression and histopathology. Using a second-generation adenovirus, recombinant
      gene stability was prolonged and associated with a diminished level of
      perivascular inflammation as compared to first-generation vectors. Markedly
      diminished levels of hexon protein were present in tissues infected with second
      generation as compared to first-generation virus. No evidence of viral shedding
      was evident. Furthermore, coadministration of first- and second-generation
      adenovirus did not affect the stability of transgene expression from the second
      generation virus. These data suggest that second-generation adenoviral vectors
      provide an improved gene delivery vehicle, and thus may be useful in gene therapy
      for cystic fibrosis.

PMID- 7578406
TI  - Expression of biologically active human factor IX in human hematopoietic cells
      after retroviral vector-mediated gene transduction.
AB  - Gene therapy is a potential treatment for hemophilia, wherein cells transduced
      with a normal factor IX gene could provide a continuous in vivo source of
      circulating factor IX. In this study, we examined the potential use of
      hematopoietic cells as a target for factor IX gene therapy. Human myeloid
      leukemia cells (HL-60) were transduced by retroviral vectors carrying a normal
      human factor IX cDNA under control of either the Moloney murine leukemia virus
      long terminal repeat (MoMuLV LTR) (LIXSN), the SV40 promoter (LNSVIX), or a
      cytomegalovirus (CMV) promoter (LNCIX). Factor IX production was measured in the
      transduced cells both in the uninduced state and after induction of granulocytic
      differentiation [with dimethylsulfoxide (DMSO)] or monocytoid differentiation
      [with phorbol myristic acetate (PMA)]. Transcription of factor IX from the MoMuLV
      LTR was seen in all cells, with a two-fold increase upon differentiation.
      Induction with PMA led to an 8- to 15-fold increase in factor IX transcripts from
      an internal CMV promoter. No factor IX transcripts from the internal SV40
      promoter were detected. Immunoreactive factor IX protein was identified by
      Western blot from induced HL-60 cells transduced by either LIXSN or LNCIX. Factor
      IX production by HL-60 cells transduced by LNCIX ranged from 38-93 ng/10(6)
      cells/24 hr following induction of monocytic differentiation. The factor IX
      antigen titer was directly related to factor IX coagulant titer (r = 0.98; p <
      0.001). These data indicate that human myelomonocytic cells are capable of
      performing the necessary post-translational modifications to produce functional
      factor IX.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578407
TI  - Transcriptional regulatory sequences of carcinoembryonic antigen: identification
      and use with cytosine deaminase for tumor-specific gene therapy.
AB  - The 5' sequences from the human carcinoembryonic antigen gene (CEA) were analyzed
      using luciferase reporter gene assays. This analysis identified important cis
      acting sequences needed for selective expression in CEA-positive cells. Over 50
      CEA/luciferase reporter clones were constructed and analyzed in two CEA-positive
      and two CEA-negative cell lines. The CEA sequences analyzed extended from the
      translational start to 14.5 kb 5' of the CEA gene. A 408-bp region from the CEA
      3' untranslated region was also examined for its effect on reporter gene
      activity. The CEA promoter was located between bases -90 and +69 of the
      transcriptional start site. Sequences between -41 and -18 were essential for
      expression from the CEA promoter. Multimerization of sequences between -89 and 
      40 resulted in copy number-related increases in both expression level and
      selectivity for CEA-positive cells. Two upstream regions of CEA, -13.6 to -10.7
      kb or -6.1 to -4.0 kb, when linked to the multimerized promoter led to high
      level, selective expression in CEA-positive cell lines. Several CEA/luciferase
      constructs demonstrated 80- to 120-fold higher expression in CEA-positive cell
      lines compared to expression in CEA-negative Hep3B cells. The expression from
      these constructs was quite strong in CEA-positive cells, being two- to four-fold
      higher than an SV40 enhancer/promoter construct. The most promising CEA
      transcriptional regulatory sequences were used to regulate the expression of
      cytosine deaminase (CD) in stable cell lines. The expression of CD was assessed
      directly by an enzymatic assay and indirectly by determining the in vitro IC50 to
      5-fluorocytosine (5FC). The chimeric gene pCEA/CD-145 displayed the desired
      expression spectrum--high-level expression in the CEA-positive cells and low
      level expression in CEA-negative cells. CD expression from this chimera
      correlated well with the expression of the endogenous CEA gene. Treatment of mice
      bearing NCI H508 pCEA/CD-145 tumor xenografts with 5FC lead to significant
      antitumor effects in vivo. The CEA/CD chimeric gene should be useful for tumor
      specific suicide gene therapy of CEA-positive tumors.

PMID- 7578410
TI  - Long-term expression of the biologically active growth hormone in genetically
      modified fibroblasts after implantation into a hypophysectomized rat.
AB  - We employed the hypophysectomized rats as an animal model to explore the
      feasibility of using genetically engineered fibroblast cells for growth hormone
      gene therapy. An internal ribosome entry site (IRES)-directed bicistronic
      retroviral vector, PSN, which contained a porcine growth hormone (pGH) cDNA at
      the first cistron and a Neo(r) gene at the second cistron was used to infect
      primary rat embryo fibroblast (REF) cells. The infected cells (5 x 10(6)
      cells/rat) were injected directly into the peritoneum of syngeneic
      hypophysectomized rats. We demonstrate that the implanted PSN-infected REF cells
      could secrete biologically active pGH in vivo, leading to significant growth of
      the tibia at day 15 and day 57 post-implantation. We also treated the PSN
      infected REF cells with collagen to form a tissue-like structure. The skin-like
      discs were grafted underneath the skin on the back of rats and cells were
      retrieved at different times. Using two criteria, semiquantitative reverse
      transcription-polymerase chain reaction on the pGH RNA extracted from the
      explants and G418 resistance conferred from the explanted cells, we demonstrate
      that pGH was expressed in the implanted fibroblasts up to 70 days. Despite the
      fact that the total pGH RNA level was reduced in the explants of long-time post
      implantation, which was probably due to the reduction of transduced cells
      retained in the explants, the specific efficiencies of pGH RNA expression from
      these explants were maintained as high as the primary PSN-infected REF prior
      implantation. These results suggest that fibroblast cells are capable of
      expressing the foreign genes persistently in vivo.

PMID- 7578409
TI  - Retroviral coexpression of a multidrug resistance gene (MDR1) and human alpha
      galactosidase A for gene therapy of Fabry disease.
AB  - Human alpha-galactosidase A (alpha-Gal A; EC.3.2.1.22) is a lysosomal
      exoglycosidase encoded by a gene on Xq22. Deficiencies of this enzyme result in
      Fabry disease, an X-chromosome-linked recessive disorder that leads to premature
      death in affected males. For treatment of genetic diseases, we have developed a
      retroviral vector system, pSXLC/pHa, that enables coexpression of drug-selectable
      markers with a second nonselectable gene as part of a bicistronic message using
      the promoter from the Harvey murine sarcoma virus and an internal ribosomal entry
      site (IRES) from encephalomyocarditis virus. Retroviral vectors based on this
      system that carry the human alpha-Gal A cDNA either upstream (pHa-alpha Gal-IRES
      MDR) or downstream (pHa-MDR-IRES-alpha Gal) from the IRES relative to the drug
      selectable MDR1 (P-glycoprotein) cDNA were constructed. Each of eight independent
      vincristine-resistant, pHa-alpha Gal-IRES-MDR-transfected clones and all four
      vincristine-resistant, pHa-alpha Gal-IRES-MDR retrovirus-transduced clones showed
      significantly higher activity of alpha-Gal A than the parental cells. More than
      50% of the vincristine-resistant, pHa-MDR-IRES-alpha Gal-transfected clones and
      all four vincristine-resistant, pHa-MDR-IRES-alpha Gal retrovirus-transduced
      clones showed significantly higher activity of alpha-Gal A than the parental
      cells. In these bicistronic vectors, the cDNA whose translation was cap-dependent
      (upstream) was expressed at higher levels than when the same cDNA was translated
      in an IRES-dependent manner (downstream). These vectors may prove useful in the
      gene therapy of Fabry disease.

PMID- 7578411
TI  - The treatment of ovarian cancer with a gene modified cancer vaccine: a phase I
      study.

PMID- 7578408
TI  - Intratracheal gene delivery with adenoviral vector induces elevated systemic IgG
      and mucosal IgA antibodies to adenovirus and beta-galactosidase.
AB  - One major concern about using adenoviral vectors for repetitive gene delivery to
      lung epithelial cells is the induction of an immune response to the vector, thus,
      impeding effective gene transduction. To assess the immune response to the
      adenoviral vector, repetitive intratracheal (i.t.) gene dosing was performed in
      CD-1 mice using the replication-deficient adenovirus 5 (Ade5) vector carrying the
      lacZ gene, and compared to the antibody responses induced by conventional
      intranasal (i.n.) and intraperitoneal (i.p.) routes of immunization. Kinetics of
      serum IgG, IgA, and IgM antibody responses to the adenoviral vector and to beta
      galactosidase (beta-Gal) were evaluated. Two or three adenoviral vector doses
      given by i.t., i.n., or i.p. routes resulted in serum IgG titers in excess of
      1:200,000, whereas serum IgM and IgA were moderately induced. Analysis of the
      predominant murine IgG subclass was determined to be IgG2b and IgG2a. To
      determine the localization of this antibody response, the ELISPOT assay was
      employed. Lymphocytes were isolated from the lung, the lower respiratory lymph
      nodes (LRLN), the nasal passages (NP), and the spleen. For i.t- and i.n.
      administered mice, the highest IgA spot-forming cell (SFC) response to Ade5 and
      beta-Gal was located in the NP and in the lung. Both the lung and the LRLN showed
      elevated numbers of IgG SFCs (4- to 12-fold greater than splenic IgG SFC
      response) for Ade5 and beta-Gal. This evidence suggests that the lung and
      associated lymphoid tissues were the source for serum antibodies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578412
TI  - An open label, phase I/II clinical trial to evaluate the safety and biological
      activity of HIV-IT (V) (HIV-1IIIBenv/rev retroviral vector) in HIV-1-infected
      subjects.

PMID- 7578413
TI  - Tap-1 and Tap-2 gene therapy selectively restores conformationally dependent HLA
      Class I expression in type I diabetic cells.
AB  - Genetic susceptibility to many autoimmune diseases, including insulin-dependent
      diabetes mellitus (IDDM) is statistically linked to the HLA class II region of
      chromosome 6. However, a distinguishing feature of patients with HLA class II
      linked autoimmune disease is an abnormally low density of conformationally
      correct, self-peptide filled HLA class I molecules on the lymphocyte cell
      surface. The transporters associated with antigen processing (Tap-1 and Tap-2)
      are essential for normal class I expression and presentation of intracellular
      peptides, and these genes are located within the HLA class II region. The aims of
      this project were to determine if Tap genes could be implicated in the defective
      class I expression associated with IDDM by using a novel Epstein-Barr virus (EBV)
      mediated gene transfer system to introduce a cloned, normal Tap-2 or Tap-1 gene
      into B cell lines from normal and IDDM patients and analyzing the effect on
      conformationally dependent class I expression. The results show that Tap-2 gene
      transfer in B cells from 40% of randomly selected IDDM patients increased
      expression of conformationally correct, cell-surface class I molecules to levels
      comparable with similarly treated B cells from normal control individuals. B
      cells from another 40% of IDDM patients responded to Tap-1 gene transfer. These
      effects were specific because B cells from normal individuals did not respond to
      Tap-1 or Tap-2 gene transfer with increased class I expression, and B cells from
      IDDM patients responding to Tap-2 gene transfer did not respond to Tap-1 gene
      transfer and vice versa. Thus, these complementation studies identify distinct,
      non-overlapping subsets of IDDM patients whose class I defect in B cells can be
      reversed by Tap-1 or Tap-2 gene transfer. The increase in class I expression
      induced by Tap gene transfer is associated with a reduction in the number of
      peptide-empty class I molecules as demonstrated by the response to exogenous
      peptide loading. Furthermore, the increase in self-peptide filled class I
      molecules induced by Tap gene transfer into B cells from IDDM patients is
      associated with restored antigen presentation to autologous T cells. These
      studies conclude that Tap gene dysfunctions may contribute to the defect in class
      I phenotype and antigen presentation demonstrated by IDDM patients. Defective
      presentation of self-peptides by antigen presenting cells can lead to the failed
      T cell education and tolerance to self antigens evident in IDDM. These studies
      functionally identify HLA class II region genes that contribute to an immunologic
      defect in IDDM.

PMID- 7578414
TI  - Adenovirus-mediated gene transfer to the respiratory tract of fetal sheep in
      utero.
AB  - Many human genetic diseases, such as congenital surfactant protein B deficiency,
      manifest in the perinatal period. Prenatal gene therapy may be necessary to
      minimize morbidity in these diseases. We hypothesized that bacterial beta
      galactosidase (beta-Gal) gene could be transferred to and expressed in the
      pulmonary epithelium of fetal sheep in utero using a replication-deficient
      adenovirus (Av1LacZ4). We instilled Av1LacZ4 (1.5 x 10(11) plaque-forming units,
      n = 10) or saline (n = 2) intratracheally to chronically instrumented fetal sheep
      at 112-134 days gestation (term = 145 days). Lung fluid was collected before and
      after Av1LacZ4 administration for cytological analysis. Lung tissue was examined
      for transgenic beta-Gal activity and evidence of toxicity. Transgenic beta-Gal
      activity was visualized as blue nuclear staining of tissue treated with X-Gal and
      was detected in the lungs of 5 animals for up to 14 days after administration.
      Transgenic beta-Gal activity was not detected in the lungs of animals analyzed
      beyond 14 days after treatment. Pulmonary histopathology was detected in most
      Av1LacZ4-treated animals and manifested as a mixed cellular infiltrate consisting
      of neutrophils, macrophages, and lymphocytes. Fetal lung fluid analysis revealed
      a predominantly lymphocytic response in most Av1LacZ4-treated animals within 3
      days (2.88 x 10(6) vs. 4 x 10(3) total cells/ml in control animals). We have
      demonstrated that adenovirus vectors can direct gene transfer to the lungs of
      fetal sheep in utero. The transferred gene expression was transient and possibly
      limited by the induced inflammatory response.

PMID- 7578415
TI  - A modified urokinase plasminogen activator induces liver regeneration without
      bleeding.
AB  - Direct retrovirus-mediated hepatic gene transfer results in permanent gene
      expression; however, gene transfer requires surgical hepatectomy (to stimulate
      cell division) and has been inefficient. We recently used recombinant adenovirus
      vectors that transiently expressed urokinase from mouse hepatocytes to induce
      hepatocellular regeneration in place of a partial hepatectomy. The adenovirus
      method allowed for five-fold more efficient retrovirus transduction in vivo
      compared to the conventional partial hepatectomy approach. The major problem with
      the urokinase-mediated hepatic regeneration was the transient secretion of
      urokinase into the bloodstream that led to hypocoagulation. To circumvent this
      side-effect, the urokinase protein was modified by adding amino-terminal and
      carboxy-terminal endoplasmic reticulum retention signals. The recombinant
      urokinase molecules expressed from adenoviral vectors remained in hepatocytes,
      were enzymatically active, and resulted in similar rates of hepatic regeneration
      as found with the secreted urokinase. Modified urokinase-mediated liver
      regeneration was equally capable of allowing retrovirus-mediated gene transfer in
      vivo. Thus, the method of direct retrovirus transduction of hepatocytes becomes
      clinically relevant as the technology becomes safer.

PMID- 7578416
TI  - Gene therapy for hemophilia B: host immunosuppression prolongs the therapeutic
      effect of adenovirus-mediated factor IX expression.
AB  - Hemophilia B is caused by a deficiency of blood clotting factor IX (FIX).
      Previous studies have shown that the delivery of a recombinant adenoviral vector
      expressing canine FIX (cFIX) resulted in a complete correction of hemophilia B in
      FIX-deficient dogs, but that cFIX expression decreased to only about 1-2% of
      normal levels 3 weeks after treatment. In the present study, therapeutic levels
      of cFIX expression capable of producing a partial correction of hemophilia B were
      maintained for at least 6 months after the coadministration of the cFIX
      expressing adenovirus and the immunosuppressive agent cyclosporin A (CsA). These
      findings support a recent report (Yang et al., 1994) that host T-cell-mediated
      immunity against virally transduced cells is a major contributing factor to the
      transient nature of adenovirus-mediated gene expression in immunocompetent
      animals. Although a second administration of the cFIX-expressing adenovirus 6
      months after the first infusion had only a minimal effect on plasma FIX levels in
      a dog that had been continuously treated with CsA, the prolonged expression of
      the transgene indicates that immunosuppression may be applicable in attaining
      long-term treatment of clinically relevant disorders.

PMID- 7578417
TI  - Effect of adenoviral vector infection on cell proliferation in cultured primary
      human airway epithelial cells.
AB  - Although recombinant adenoviruses are used as vectors for delivering therapeutic
      genes to the airways of cystic fibrosis (CF) patients, the effects of these
      vectors on the kinetics of airway epithelial cell growth have not been
      investigated. We tested whether E1, E3-deleted Ad vectors (Ad5-CMV-lacZ) affect
      the kinetics of cell proliferation of human airway epithelial cells in primary
      culture. There was a dose-dependent relationship between the vector multiplicity
      of infection (moi) and the efficiency of Ad-mediated lacZ gene transfer. Growth
      curves of cells exposed to vector were shifted to the right as compared to
      vehicle in a dose-dependent manner. The vector-induced slowing of cell
      proliferation resulted from both (i) increased apoptotic cell death and (ii)
      lower recruitment into S phase. UV inactivation of the vector genes abolished the
      effects on cell proliferation. These data demonstrate that as the moi of vectors
      is increased to achieve effective gene transfer, apoptosis and slowing of the
      cell cycle of infected cells increases concomitantly. The identification and
      inactivation of these vector effects on human airway cells may be important for
      reducing the toxicity of adenovirus vectors for gene therapy of CF airways.

PMID- 7578418
TI  - In vivo adenovirus-mediated gene transfer of the Escherichia coli cytosine
      deaminase gene to human colon carcinoma-derived tumors induces chemosensitivity
      to 5-fluorocytosine.
AB  - To evaluate the concept that in vivo transfer of the Escherichia coli cytosine
      deaminase gene will confer sensitivity of a solid tumor to the prodrug 5
      fluorocytosine (5FC), we constructed an adenovirus vector (AdCMV.CD) carrying the
      cytosine deaminase gene driven by the cytomegalovirus (CMV) promoter, infected
      HT29 colon carcinoma cells in vitro and in vivo, and evaluated cell growth over
      time. AdCMV.CD produced a functional cytosine deaminase protein in HT29 cells in
      vitro as evidenced by the ability of lysates from the infected cells to convert
      [3H]5FC to its active metabolite 5-fluorouracil (5FU). The AdCMV.CD vector
      effectively suppressed HT29 cell growth in vitro in the presence of 5FC in a dose
      dependent manner. Infection with AdCMV.CD, when as few as 10% of cells expressed
      the cytosine deaminase gene, was associated with a bystander effect when combined
      with 5FC in cell mixing studies. Further, this bystander effect was not dependent
      on cell-to-cell contact as demonstrated by suppression of [3H]thymidine
      incorporation in HT29 cells when supernatant from AdCMV.CD-infected cells treated
      with 5FC was transferred cells. Consistent with these in vitro observations, when
      AdCMV.CD was directly injected into established subcutaneous HT29 tumors in nude
      mice receiving 5FC, there was a four-fold reduction in tumor size at day 15
      compared to controls, and a five-fold reduction at day 28. These observations
      suggest that adenovirus-mediated gene transfer of the E. coli cytosine deaminase
      gene and concomitant administration of 5FC may have potential as a strategy for
      local control of the growth of tumor cells susceptible to 5FU.

PMID- 7578419
TI  - Fluorescence-based selection of retrovirally transduced cells in the absence of a
      marker gene: direct selection of transduced type B Niemann-Pick disease cells and
      evidence for bystander correction.
AB  - Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders
      resulting from the deficient activity of acid sphingomyelinase (ASM). Type A NPD
      is characterized by the absence of residual ASM activity, massive accumulation of
      sphingomyelin and cholesterol within lysosomes, and a rapid, neurodegenerative
      course that leads to death by 3 years of age. In contrast, type B NPD patients
      have low, but detectable, levels of residual ASM activity and little or no
      neurologic disease. Thus, individuals with type B NPD may survive into late
      adolescence or adulthood and are considered excellent candidates for somatic cell
      gene therapy. To facilitate the development of gene therapy for this disorder, a
      novel procedure was devised to isolate metabolically corrected type B NPD cells
      in the absence of marker gene expression. Type B NPD cells were transduced with
      retroviral vectors expressing ASM, labeled with lissamine rhodamine sphingomyelin
      (LR-SPM), and subjected to preparative fluorescence-activated cell sorting
      (FACS). Two non-overlapping cell populations were isolated, corresponding to
      enzymatically corrected (i.e., low fluorescence) and noncorrected (i.e., high
      fluorescence) cells. Quantitative PCR analysis demonstrated that the
      enzymatically corrected cells were enriched for vector sequences. Moreover, the
      corrected cells could be regrown and continued to express high levels of ASM
      activity after numerous passages, consistent with the fact that they were stably
      transduced. Notably, coculture of FACS-sorted, overexpressing cells with
      untreated type B NPD fibroblasts resulted in a homogeneous cell population with
      low fluorescence whose FACS distribution overlapped that of the corrected cells.
      Computerized fluorescence microscopy confirmed that nearly all of these
      cocultured cells expressed ASM activity and could hydrolyze LR-SPM.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578420
TI  - Aerosol delivery of a beta-galactosidase adenoviral vector to the lungs of
      rodents.
AB  - Aerosol delivery of adenoviral vectors is of particular interest in regard to
      gene therapy for cystic fibrosis (CF), with potential advantages of more uniform
      respiratory delivery, a less invasive approach, and ease of repetition. The
      AdHCMVsp1LacZ (AdLacZ) adenoviral vector was used to evaluate the feasibility of
      aerosol delivery to the respiratory epithelium in rodents. The adenoviral vector
      tolerated aerosol generation as measured by recovery in an all-glass impinger.
      Using an Andersen sampler to mimic the human respiratory tract, aerosol particles
      were found to have an average mass mean aerodynamic diameter of 1.6 microns and a
      geometric standard deviation of 1.7 microns. Cotton rats and mice exposed to
      viral aerosols demonstrated beta-galactosidase expression in up to 10-30% of the
      epithelial surface of the small and large airways, whereas expression in Sprague
      Dawley rats was largely limited to the alveolar epithelium. Transgene expression
      was distributed uniformly through both lungs in animals treated by aerosol. The
      variables for aerosol delivery are complex and include viral titer, aerosol
      device, duration of exposure, species of recipient, and respiratory behavior
      among other factors. Species differences in expression in airways as compared to
      alveolar epithelium have important implications for clinical application.

PMID- 7578421
TI  - Genetic modification of human peripheral blood lymphocytes with a transdominant
      negative form of Rev: safety and toxicity.
AB  - A transdominant mutant form of the rev gene, M10, confers resistance to infection
      by the human immunodeficiency virus (HIV) in vitro and is currently under
      investigation as a potential intervention in acquired immunodeficiency syndrome
      (AIDS). In this report, we examine three issues relevant to the safety of
      autologous transfer of human T cells genetically modified with Rev M10. First,
      the potential for malignant transformation was assessed in vitro using
      interleukin-2 (IL-2) dependence and fibroblast transformation assays, and
      tumorigenicity was evaluated in severe combined immunodeficient (SCID) mice.
      Possible toxicity was evaluated by pathologic analysis following adoptive
      transfer of genetically modified human T cells into SCID mice. Second, methods
      were developed that permit T cell activation required for gene transfer but do
      not allow replication of endogenous HIV. Third, T cell function was evaluated in
      peripheral blood lymphocytes (PBL) of HIV-seropositive donors transduced with Rev
      M10 and compared to a negative control mutant, delta Rev M10. By all criteria, no
      oncogenicity or toxicity was observed. Human T cells transduced with these
      vectors did not grow in the absence of IL-2 in vitro, and no tumors were observed
      following transplantation of genetically modified human cells into recipient SCID
      mice. Histopathological analysis of heart, lung, liver, spleen, and kidney of
      animals 1-21 weeks following adoptive transfer of gene-modified human T cells
      revealed no significant abnormalities. Additionally, no differences were observed
      in the pattern of cytokine secretion in enriched human PBL expressing Rev M10
      compared to delta Rev M10. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578422
TI  - Dissection of ADP-ribose polymer synthesis into individual steps of initiation,
      elongation, and branching.
AB  - We have studied the automodification reaction of poly(ADP-ribose)polymerase
      (PARP) (EC 2.4.2.30). The individual reactions of initiation, elongation, and
      branching catalyzed by this enzyme have been dissected out by manipulating the
      concentration of beta NAD, the ADP-ribosylation substrate. While PARP-mono(ADP
      ribose) conjugates were the predominant products of automodification at 200 nM
      NAD (initiation), highly branched and complex polymers were synthesized at 200
      microM NAD (polymerization). Initial rates of automodification increased with
      second order kinetics as a function of the enzyme concentration at both 200 nM
      and 200 microM NAD. These results are consistent with the conclusion that two
      molecules of PARP are required for ADP-ribose polymer synthesis during enzyme
      automodification. Thus, the auto-poly(ADP-ribosyl)ation reaction of PARP is
      intermolecular. In agreement with this notion, we observed that initial rates of
      the initiation reaction with 3'-deoxyNAD as a substrate also increased with the
      square of the enzyme concentration. In addition, the auto-poly(ADP-ribosyl)ation
      reaction of PARP increased with second order kinetics as a function of the NAD
      concentration at nanomolar levels (0.2-106 microM). Therefore, the dimeric
      structure of PARP also requires two molecules of bound NAD for efficient ADP
      ribose polymerization.

PMID- 7578424
TI  - Interactions of poly(ADP-ribose) with nuclear proteins.
AB  - The molecular mechanisms whereby poly(ADP-ribosyl)ation primes chromatin proteins
      for an active role in DNA excision repair are not understood. The prevalent view
      is that the covalent linkage of ADP-ribose polymers is essential for the
      modification of target protein function. By contrast, we have focused on the
      possibility that ADP-ribose polymers interact non-covalently with nuclear
      proteins and thereby modulate their function. The results show that ADP-ribose
      polymers engage in highly specific and strong non-covalent interactions with a
      small number of nuclear proteins, predominantly histones, and among these only
      with specific polypeptide domains. The binding affinities were largely determined
      by two factors, ie the polymer sizes and the presence of branches. This provides
      an explanation for the target specificity of the histone shuttle mechanism that
      was previously reported by our laboratory. Interestingly, the polymer molecules
      being most effective in protein targeting in vitro, are strictly regulated in
      mammalian cells during DNA repair in vivo.

PMID- 7578425
TI  - Biochemical properties and function of poly(ADP-ribose) glycohydrolase.
AB  - We describe here the latest observations on poly(ADP-ribose) glycohydrolase.
      There is now extensive evidence that this nuclear enzyme is an endo
      exoglycosidase which has a key role to perform in the removal of polymers which
      interact with proteins through covalent and non-covalent interactions. Also, we
      have developed a zymogram which will permit the isolation of the various isoforms
      of the glycohydrolase and the eventual cloning of this enzyme. Finally, we have
      evidence that very short oligomers and even monomers of ADP-ribose covalently
      bound to proteins can be removed by poly(ADP-ribose) glycohydrolase.

PMID- 7578423
TI  - The role of inhibitors of poly(ADP-ribose) polymerase as resistance-modifying
      agents in cancer therapy.
AB  - Poly(ADP-ribose) polymerase (PARP) plays an important role in a number of
      cellular processes including DNA repair. Since poly(ADP-ribosyl)ation occurs in
      response to radiation- or drug-induced DNA damage, inhibitors of the enzyme may
      enhance the antitumour activity of radiotherapy or cytotoxic drug treatment. In
      this review the development of PARP inhibitors is discussed, and structure
      activity relationships amongst inhibitors of the enzyme are presented. Studies to
      date regarding the in vitro and in vivo activity of PARP inhibitors, as
      resistance modifying agents in cancer therapy, are also overviewed.

PMID- 7578426
TI  - Model systems for the study of the role of PADPRP in essential biological
      processes.
AB  - The nuclear enzyme poly(ADP-ribose) polymerase (PADPRP) is implicated in a number
      of cellular processes, including DNA repair, replication, and differentiation. We
      have been using several model systems to examine these potential roles of PADPRP.
      A human keratinocyte model system has been developed in which stable lines of
      epidermal cells contain an inducible construct harboring the antisense cDNA to
      PADPRP. When PADPRP antisense RNA is induced in culture, endogenous PADPRP mRNA,
      protein, and enzymatic activity is lowered, and the pattern of poly(ADP)
      ribosylation in response to alkylating agents is altered. When keratinocyte
      clones containing the antisense construct or empty vector alone were grafted onto
      nude mice, they formed histologically normal human skin. The PADPRP antisense
      construct was also inducible in vivo by the topical application of dexamethasone
      to the reconstituted epidermis, as determined by in situ hybridization. In
      addition, poly(ADP-ribose) polymer could be induced and detected in vivo
      following the topical application of a DNA alkylating agent to the grafted
      transfected skin layers. Thus, a model system has been developed in which the
      levels of PADPRP can be selectively manipulated in human keratinocytes in cell
      culture, and potentially in reconstituted epidermis as these keratinocyte lines
      can be grafted to nude mice, whereupon they form a histologically and
      immunocytochemically normal human epidermis. Another system that we have been
      utilizing to examine the role of PADPRP in proliferation and differentiation is
      stable lines of mouse preadipocytes that contain an inducible antisense PADPRP
      RNA. Similar to the keratinocyte system, these cells can inducibly express
      antisense PADPRP RNA, and subsequently lower levels of endogenous
      PADPRP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578427
TI  - On the biological role of the nuclear polymerizing NAD+: protein(ADP-ribosyl)
      transferase (ADPRT): ADPRT from Dictyostelium discoideum and inactivation of the
      ADPRT gene in the mouse.
AB  - Two approaches have been used to elucidate the role of the nuclear polymerizing
      NAD+:protein(ADP-ribosyl)-transferase (ADPRT): i) comparison of the primary
      structure of Dictyostelium discoideum ADPRT derived from a 2 kb, partial cDNA
      sequence with the mammalian, fish, amphibian and insect counterparts revealed an
      overall homology of 25%. Whereas the automodification domain was not conserved at
      all, the NAD+ binding domain (aa 859-908) showed more than 70% identical amino
      acids in all species. Together with the similar enzymatic properties of the
      ADPRTs the genetic conservation underlined the notion that ADPRT plays a major
      role in various cellular processes; and ii) inactivation of the ADPRT gene in
      murine embryonic stem cells by homologous recombination led to mouse strains with
      a complete lack of nuclear poly(ADP-ribosyl)ation. These ADPRT mutant mice were
      viable and fertile indicating that ADPRT is dispensable in mouse development.
      Moreover, repair of UV and MNNG induced DNA damage was not affected in ADPRT/3T3
      like fibroblasts, as measured by reactivation of in vitro damaged reporter
      plasmids and unscheduled DNA synthesis. However, about 30% of the ADPRT mutant
      mice developed pathological skin aberrations on a mixed 129/Sv x C57B1/6 genetic
      background. These mice will be extremely useful to define the precise biological
      role of poly(ADP-ribosyl)ation.

PMID- 7578428
TI  - Molecular genetic systems to study the role of poly(ADP-ribosyl)ation in the
      cellular response to DNA damage.
AB  - To study biological functions of poly(ADP-ribose) polymerase (PARP), low
      molecular-mass inhibitors have been used extensively, and the experimental
      results obtained led to the view that PARP plays a role in DNA repair as well as
      in other cellular processes, eg DNA replication, cell proliferation, and
      differentiation. Accumulating evidence that these inhibitors have side effects on
      other metabolic pathways prompted us to develop two molecular genetic systems for
      the modulation of poly(ADP-ribosyl)ation in living cells: i) the first approach
      is centered on the DNA-binding domain (DBD) of PARP, which recognizes DNA strand
      breaks through its zinc fingers, leading to enzyme activation. We have
      established stable cell culture systems for either constitutive or inducible
      overexpression of the DBD. In these cells we observe a drastic trans-dominant
      inhibition of poly(ADP-ribosyl)ation which is associated with sensitization of
      cells to gamma-irradiation; and ii) in an attempt to specifically increase the
      poly(ADP-ribose) formation capacity in living cells, the hamster cell line CO60
      was stably transfected to obtain constitutive overexpression of full-length human
      PARP. These molecular genetic systems may be useful for the elucidation of the
      precise role of poly(ADP-ribosyl)ation in the biological response to DNA damage.

PMID- 7578429
TI  - Poly(ADP-ribose) polymerase: structure-function relationship.
AB  - Dissection of the human poly(ADP-ribose) polymerase (PARP) molecule in terms of
      its structure-function relationship has proved to be an essential step towards
      understanding the biological role of poly(ADP-ribosylation) as a cellular
      response to DNA damage in eukaryotes. Current approaches aimed at elucidating the
      implication of this multifunctional enzyme in the maintenance of the genomic
      integrity will be presented.

PMID- 7578430
TI  - Role of poly(ADP-ribose) polymerase in cell-cycle checkpoint mechanisms following
      gamma-irradiation.
AB  - A nuclear poly(ADP-ribose) polymerase (PARP) is activated by gamma-irradiation
      and consequently synthesizes poly(ADP-ribose) by binding to DNA strand-breaks.
      This property suggests that PARP is a DNA strand-break-signal generator.
      Meanwhile, the cell-cycle arrest occurs in G1 and G2 phases following gamma
      irradiation. We found that PARP inhibitors including 3-aminobenzamide (3-AB)
      suppressed G1 arrest and enhanced G2 arrest following gamma-irradiation. These
      observations suggested that PARP is critical for the induction of G1 arrest and
      is also involved in the regulation of G2 arrest. Furthermore, the effects of 3-AB
      on the G1-arrest signal-transduction pathway were also studied. We found that p53
      stabilization following gamma-irradiation was not inhibited but the p53
      responsive transient increases of WAF1/CIP1/p21 and MDM-2 mRNA were suppressed by
      3-AB. Therefore, it is suggested that PARP participates in G1-arrest signal
      transduction pathway through the modulation of WAF1/CIP1/p21 and MDM-2 mRNA
      expression.

PMID- 7578432
TI  - Effect of poly(ADP-ribose) synthetase on the expression of major
      histocompatibility complex (MHC) class II genes.
AB  - We have studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma
      (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class
      II molecules. We constructed an expression plasmid capable of expressing either a
      sense RNA (MT-ARS) or an antisense RNA (pAS-FL or pAS-5') for poly(ADP-ribose)
      synthetase. We transfected the plasmid into mouse or human macrophage tumor cells
      and examined the effect on the expression of MHC class II molecules. The IFN
      gamma-inducible expression of MHC class II gene was considerably reduced in
      transformant clones (A-2, B-2), in which the synthetase was highly expressed,
      whereas the depletion of the synthetase due to the expression of antisense RNA
      for the synthetase amplified the expression of MHC class II molecules. The
      results indicate that the level of the synthetase critically regulates the IFN
      gamma-inducible MHC class II molecules. Next, we analyzed DNase I hypersensitive
      sites (DHS) of mouse MHC class II, I-A beta gene and found two sites, one in the
      promoter region and the other one in the first intron. The DHS in first intron
      was less sensitive towards DNase I attack in transformant clones (A-2, B-2) in
      which the synthetase was synthesized in a large quantity. Thus we constructed two
      beta-galactosidase reporter genes, one (A beta 2.0kb-lac z) containing the
      promoter region to a part of the second exon of the class II gene, and the other
      (A beta pro-lac z) containing the promoter region of the class II gene alone. The
      expression of the reporter gene was analyzed by reverse transcriptase-polymerase
      chain reaction (RT-PCR) and found that the expression of A beta 2.0kb-lac z was
      suppressed in the transformant clones (A-2, B-2) relevant to control cells but
      the expression of A beta pro-lac z was the same level among those cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578435
TI  - [VII Scientific meeting of the Faculty of Medicine, VIII Congress of the Academy
      of Medicine of Zulia, III anniversary meeting of the Medical Genetics Department.
      Maracaibo, Venezuela, 23-27 July 1995. Abstracts].

PMID- 7578433
TI  - Regulation of the human poly(ADP-ribosyl) transferase promoter via alternative
      DNA racket structures.
AB  - Human nuclear poly(ADP-ribosyl) transferase (ADPRT) protein content in cells
      suggests that ADPRT expression is stringently controlled. Analysis of the 3 kb
      promoter sequence, which is required for high level expression, revealed an
      extraordinary architecture: several Sp1 motifs are located in the vicinity of the
      first exon but the closest CCAAT/TATA boxes are several hundred basepairs away.
      Four Alu type repetitive sequences are in the promoter structure. Within these
      Alu sequences there exist inverted repeat elements, which could form two mutually
      exclusive types of DNA tertiary structure consisting of quadruplex DNA and loops
      resembling rackets. Thereby, a CCAAT/TATA element would be moved to spatial
      vicinity of the Sp1 site activating the promoter. Deletion analysis showed the
      functional significance of these racket elements. We also obtained evidence for
      DNA racket structures when we studied mutational mechanisms in a human adenine
      phosphoribosyltransferase (APRT) deficient patient. One of his alleles harbours a
      novel complex type of deletion/insertion mutation. Based on several highly
      informative sequence features in this genomic region a model is proposed for the
      generation of this unusual type of mutation involving two steps: an initial
      targeting step and a subsequent complex rearrangement. This process includes the
      formation of a DNA racket structure, which resembles that of the ADPRT promoter.
      Thus we conclude that DNA racket structures seem to be of general importance in
      nature.

PMID- 7578436
TI  - Behavioural consequences of frontal cortex grafts and enriched environments after
      sensorimotor cortex lesions.
AB  - Past studies have experienced difficulty in achieving graft survival and
      behavioural recovery after sensorimotor cortex lesions. In the present work,
      adult female rats trained preoperatively to cross a narrow beam for food reward
      were maintained in standard group cages or an enriched environment, commencing
      one week after a unilateral lesion. One month post-lesion, half of these rats
      received multiple suspension grafts of (E20) fetal frontal cortex, placed
      adjacent to the lesion cavity, and 8 days later recovery of beam-walking skills
      was examined for a six-week period. The grafts survived in all cases with an
      appropriate lesion, a notable result given the one month lesion-graft delay, but
      graft volume was not influenced by postoperative environment. The substantial
      lesion-induced deficits evident just prior to differential housing showed a
      marked reduction by the start of post-graft testing, but relative to intact
      controls a persistent deficit in foot slip errors occurred in all lesion groups.
      Irrespective of graft status, postoperative enrichment prevented the occurrence
      of severe foot slips, especially early in retraining. The frontal grafts,
      however, enhanced beam-walking recovery by reducing the overall frequency of foot
      slips on early post-grafting sessions, an effect we suggest is related to graft
      derived trophic influences, but this measure was not significantly improved by
      postoperative enrichment.

PMID- 7578434
TI  - ADP-ribosylation reactions in plants.
AB  - Poly ADP-ribosylation is a post-translational modification of protein structure
      and function that occurs in the nucleus of most eukaryotic cells. Although its
      function has not been fully elucidated it is thought to have a role in the
      processing DNA strand breaks. Poly(ADP-ribose) polymerase, a highly conserved
      enzyme, is well studied in animal cell systems but is less well characterised in
      plants. Our present understanding of mono and poly ADP-ribosylation reactions in
      plants is reviewed in this article.

PMID- 7578431
TI  - Analysis of biological function of poly(ADP-ribosyl)ation in Drosophila
      melanogaster.
AB  - To understand the biological function of poly(ADP-ribosyl)ation of proteins, we
      have isolated and characterized the gene for poly(ADP-ribose) polymerase from
      Drosophila melanogaster. Two approaches were taken to analyze the function of the
      poly(ADP-ribosyl)ation reaction. The first is analysis of the homology of the
      amino acid sequences of poly(ADP-ribose) polymerase from phylogenetically
      different eukaryotes, namely human, mouse, bovine, chicken, Xenopus laevis and
      Drosophila melanogaster and elucidation of the conserved amino acid sequences
      that appear to be important for the function of poly(ADP-ribose) polymerase.
      Analysis of the recombinant poly(ADP-ribose) polymerase which had truncated or
      mutated motifs expressed in E coli would confirm the importance of the conserved
      amino acid sequence. The interaction of poly(ADP-ribose) polymerase with other
      proteins involved in DNA repair, replication, recombination and transcription
      will clarify the function of poly(ADP-ribosyl)ation. The second approach is to
      get the mutants which have disruption in the poly(ADP-ribose) polymerase gene and
      to analyse the phenotypes of these mutants. The characterization of these mutants
      will be discussed.

PMID- 7578437
TI  - Neuropathological sequelae of long-term allogeneic and syngeneic neural
      transplantation into the hippocampus.
AB  - The long-term fate of multiple intrahippocampal allogeneic transplants of fetal
      basal forebrain tissue was studied in neonatally tolerised and immunised groups
      of rats with lesions of the fimbria-fornix. Despite the good survival of the
      allografts in all groups, unexpected transplant-associated host hippocampal
      neuropathology was discovered 12 months after transplantation, which consisted of
      (i) CA1 cell degeneration and (ii) abnormal accumulations of phosphorylated
      neurofilaments in neuronal perikarya and axonal swellings only within the host
      hippocampal neuropil and not of the transplanted tissue. This neurofilament
      abnormality, identified by RT97 immunohistochemistry, was significantly greater
      in the transplanted rats compared to the non-grafted lesion-only and sham
      lesioned rats (p < 0.01). The same type of neurofilament abnormality was again
      observed in a second, separate experiment using unilateral and bilateral
      syngeneic and allogeneic transplants. The neuropathology was significantly (p <
      0.05) greater in the transplanted side of the unilateral transplanted rats
      compared to the non-transplanted lesion-only control side of the same animals,
      showing that transplantation per se was a major factor involved in the
      pathogenesis of this neuropathology, irrespective of the type of transplant
      (syngeneic or allogeneic). In addition, a small degree of neurofilament
      abnormality was also found within the transplants in the second experiment, but
      not in the first. The results show that, under certain conditions, specific local
      neuropathological damage to the surrounding host neural tissue can develop in
      long-surviving allografted and syngrafted animals.

PMID- 7578438
TI  - Isolation of enteric ganglia from the myenteric plexus of adult rats.
AB  - Enteric neurons and glia cells were isolated from adult Sprague Dawley rats. A
      procedure is described using a combination of microdissection and mechanical
      dissociation after enzyme treatment which yields large numbers of cell clusters
      suitable for tissue culture and grafting into the injured spinal cord.
      Differentiated enteric ganglia remained viable for at least 5 days in vitro.
      Cultured neurons expressed histochemical reactivity for acetylcholinesterase and
      nicotinamide adenine dinucleotide phosphate diaphorase. Nestin positive glia,
      which represented a population of non-myelinating enteric Schwann cells, could
      also be identified in cultures maintained 5 days or longer in vitro. The
      myenteric plexus of adult rats can provide a readily available source of neurons
      and Schwann cells for grafting to the central nervous system.

PMID- 7578439
TI  - Fibrin glue used as an adhesive agent in CNS tissues.
AB  - One of the limitations of many bridging experiments in neural transplantation is
      that the CNS tissues cannot be sutured. Fibrin glue is a two-component system
      derived from whole blood which, when mixed, reproduces the final stage of blood
      coagulation and solidifies. Many experimental studies of humans and animals show
      that fibrin glue repair of peripheral nerves is almost equivalent to
      microsurgical sutures. In this study, we attempted to extend its use to CNS
      tissues and transplants. Two techniques were tried: (1) Bilateral parietal knife
      cuts were performed by stereotaxic technique in six rats. Fibrin glue was applied
      in the right-side cortical lesion. Immunohistochemistry using antisera to
      tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), laminin and
      neurofilament (NF) was essentially similar between the control and treatment
      groups. The immunoreactivity of each marker revealed no significant differences
      between the two groups on days 1, 7 and 30. There was no difference in terms of
      gliosis or microvascular proliferation. (2) Embryonic day 16 fetal locus
      coeruleus was grafted together with E16 cortex to the anterior chamber of
      sympathectomized eyes. In the six eyes of the glue treatment group, the parietal
      cortical piece and the locus coeruleus piece were joined together before grafting
      by immersing them in the solution of fibrin glue. In the eight eyes of the
      control group, pieces of parietal cortex and locus coeruleus were introduced
      individually and approximated by gently pressing the cornea. The sizes of double
      grafts showed no significant difference between group during six weeks
      postgrafting. The immunohistochemical pictures using antisera against TH, GFAP
      and laminin were similar in both groups. Catecholaminergic fibers from the
      grafted locus coeruleus were found bridging over into the parietal cortical piece
      in both the control and treatment groups. There was no significant difference in
      TH-positive nerve fiber density between tissue glue-joined and control double
      intraocular grafts. In conclusion, fibrin glue can be used as an adhesive agent
      in CNS tissues without hampering the outgrowth of neurites or causing adverse
      tissue reactions in fetal or adult nervous tissues.

PMID- 7578440
TI  - Intracerebral implantation of hydrogel-coupled adhesion peptides: tissue
      reaction.
AB  - Arg-Gly-Asp peptides (RGD) were synthesized and chemically coupled to the bulk of
      N-(2-hydroxypropyl) methacrylamide-based polymer hydrogels. Fourier Transform
      Infrared Spectroscopy (FTIR) and amino acid analysis confirmed the peptide
      coupling to the polymer. Activated and control (unmodified) polymer matrices were
      stereotaxically implanted in the striata of rat brains, and two months later the
      brains were processed for immunohistochemistry using antibodies for glial acidic
      fibrillary protein (GFAP), laminin and neurofilaments. RGD-containing polymer
      matrices promoted stronger adhesion to the host tissue than the unmodified
      polymer matrices. In addition, the RGD-grafted polymer implants promoted and
      supported the growth and spread of GFAP-positive glial tissue onto and into the
      hydrogels. Neurofilament-positive fibers were also seen running along the surface
      of the polymer and, in some instances, penetrating the matrix. These findings are
      discussed in the context of using bioactive polymers as a new approach for
      promoting tissue repair and axonal regeneration of damaged structures of the
      central nervous system.

PMID- 7578441
TI  - Expression of nerve growth factor, brain-derived neurotrophic factor and
      neurotrophin-3 mRNAs in human cortical xenografts.
AB  - Trophic factors play an important role in the development of neurons and glia. In
      order to study the involvement of neurotrophins in human cortical development,
      human fetal parietal cortical tissue, obtained after early elective abortions,
      was transplanted to cortical cavities in immunosuppressed rats. Using in situ
      hybridization it was demonstrated that nerve growth factor, brain-derived
      neurotrophic factor and neurotrophin-3 mRNAs are expressed in developing human
      cortical xenografts. We conclude that neurotrophins may play a role in human
      cortical development and rat-derived astroglial cells could be involved in
      establishing reciprocal "permissive sites".

PMID- 7578442
TI  - Evaluation of shell vial cell culture technique for the detection of bovine
      coronavirus.
AB  - The effect of blind passage and centrifugation on the isolation of bovine
      coronavirus in human rectal tumor cells cultured in shell vials was investigated.
      A total of 68 fecal samples known to be positive for bovine coronavirus by
      transmission electron microscopic (TEM) examination were used. The samples were
      centrifuged onto human rectal tumor cell monolayers and incubated in the presence
      of trypsin. The growth of bovine coronavirus in infected cells was demonstrated
      by fluorescent antibody staining, and the extracellular virus was detected and
      confirmed by hemagglutination and hemagglutination-inhibition tests,
      respectively. Of the 68 TEM-positive samples, 51 (75%), 58 (85%), and 61 (90%)
      grew in shell vial cell cultures at first, second, and third passages,
      respectively. Of the 51 cultures positive on first passage, 19 were examined by
      TEM; 18 of these were positive for bovine coronavirus. The shell vial technique
      was also compared with direct detection of bovine coronavirus by staining
      cryostat sections of infected tissues in a direct fluorescent antibody assay. The
      results of direct fluorescent antibody assay were available for 54 of the 68
      samples, of which 53 (98%) and 43 (80%) were positive by shell vial technique and
      direct fluorescent antibody assay, respectively. For identification of bovine
      coronavirus, shell vials using human rectal tumor cells in the presence of
      trypsin is more sensitive than direct fluorescent antibody assay but is
      relatively less sensitive than transmission electron microscopy.

PMID- 7578443
TI  - Characterization of the humoral immune response to porcine reproductive and
      respiratory syndrome (PRRS) virus infection.
AB  - The development of the humoral immune response against porcine reproductive and
      respiratory syndrome (PRRS) virus was monitored by an indirect fluorescent
      antibody (IFA) test, immunoperoxidase monolayer assay (IPMA), enzyme-linked
      immunosorbent assay (ELISA), and serum virus neutralization (SVN) test over a 105
      day period in 8 pigs experimentally infected with ATCC strain VR-2402. Specific
      antibodies against PRRS virus were first detected by the IFA test, IPMA, ELISA,
      and the SVN test 9-11, 5-9, 9-13, and 9-28 days postinoculation (PI),
      respectively, and reached their maximum values by 4-5, 5-6, 4-6, and 10-11 weeks
      PI, respectively, thereafter. After reaching maximum value, all assays showed a
      decline in antibody levels. Assuming a constant rate of antibody decay, it was
      estimated by regression analysis that the ELISA, IFA, IPMA, and SVN antibody
      titers would approach the lower limits of detection by approximately days 137,
      158, 324, and 356 PI, respectively. In this study, the immunoperoxidase monolayer
      assay appeared to offer slightly better performance relative to the IFA test,
      ELISA, and SVN test in terms of earlier detection and slower rate of decline in
      antibody titers. Western immunoblot analysis revealed that antibody specific for
      the 15-kD viral protein was present in all pigs by 7 days PI and persisted
      throughout the 105-day observation period. Initial detection of antibodies to the
      19-, 23-, and 26-kD proteins varied among pigs, ranging from 9 to 35 days PI.
      Thereafter, the antibody responses to these 3 viral proteins of PRRS virus
      continued to be detected throughout the 105-day study period.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7578444
TI  - Porcine reproductive and respiratory syndrome: NEB-1 PRRSV infection did not
      potentiate bacterial pathogens.
AB  - A 2-phase study was conducted to evaluate the ability of the NEB-1 strain of
      porcine reproductive and respiratory syndrome virus (PRRSV) to potentiate common
      bacterial pathogens of swine. In phase I, 25 of 50 4-5-week-old specific-pathogen
      free (SPF) pigs were exposed to NEB-1 PRRSV (day 0). Seven days after virus
      inoculation, 8 groups received 1 of 4 bacterial pathogens: Haemophilus parasuis,
      Streptococcus suis, Salmonella cholerasuis, and Pasteurella multocida. The
      ability of NEB-1 PRRSV to produce clinical disease, viremia, neutralizing
      antibody, gross and microscopic lesions and to potentiate bacterial pathogens was
      assessed. Response to NEB-1 PRRSV was similar among inoculated pigs; prolonged
      hyperthermia, lethargy, mild to moderate dyspnea, and cutaneous erythema were
      consistent clinical signs. No clinical differences were observed in groups after
      bacterial challenge. Virus was isolated from serum at weekly intervals through
      the end of the study, and all PRRSV-inoculated pigs had seroconverted by study
      termination. Two of 5 pigs died in non-PRRSV-inoculated groups challenged with H.
      parasuis and Streptococcus suis. Mortality in PRRSV-infected pigs was limited to
      1 of 5 pigs from the Salmonella cholerasuis-challenged group. Gross lesions were
      seen in pigs dying after inoculation in H. parasuis- and Streptococcus suis
      inoculated groups, in Salmonella cholerasuis- and P. multocida-challenged pigs,
      and in 1 non-PRRSV-inoculated control pig. Microscopic lesions consisted of mild
      to moderate proliferative interstitial pneumonia, nonsuppurative myocarditis,
      lymphoid hyperplasia, and nonsuppurative encephalitis in PRRSV-inoculated pigs.
      Findings in phase I indicated that NEB-1 PRRSV does not potentiate bacterial
      disease while inducing consistent clinical signs, viremia, seroconversion, and
      microscopic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578445
TI  - Prevalence of cattle persistently infected with bovine viral diarrhea virus in 20
      dairy herds in two counties in central Michigan and comparison of prevalence of
      antibody-positive cattle among herds with different infection and vaccination
      status.
AB  - All cattle in 20 dairy herds randomly selected from herds participating in the
      Dairy Herd Improvement Association program in 2 counties in central Michigan were
      tested for the presence of bovine viral diarrhea virus (BVDV). Virus-positive
      animals were retested to ascertain persistent infection with the virus. A total
      of 5,481 animals were tested for presence of BVDV. In 9 of the herds, all animals
      were also tested for virus neutralizing antibody titer. Based on infection and
      vaccination status, these 9 herds were divided into 3 different herd categories:
      A, 5 herds with currently no cattle persistently infected (PI) with BVDV and
      without any vaccination program against BVDV in recent years; B, 2 herds with no
      current PI cattle but using killed BVDV vaccines; and C, 2 herds with PI cattle.
      PI cattle were detected in 3 out of 20 herds (15%). A total of 7 of 5,481 animals
      (0.13%) were PI. The mean prevalences of antibody carriers in herd categories A,
      B, and C were 28.8%, 76.4% and 90.6%, respectively. For one herd in category A,
      antibody analyses indicated that mostly young stock was seropositive, suggested
      recent BVDV infection in a previously closed and naive herd. Cattle in category B
      herds were vaccinated with killed vaccine from the age of 15 months. These herds
      had several antibody negative animals among the younger cows, suggesting
      incomplete protection against BVDV infection. In the 3 herds in which PI animals
      were detected, all cattle had been vaccinated with killed vaccine. The antibody
      positive animals had antibody titers that were significantly different both among
      herds and among herd categories.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578446
TI  - Application of antibody titers against bovine viral diarrhea virus (BVDV) as a
      measure to detect herds with cattle persistently infected with BVDV.
AB  - Based on the distribution of antibody titers against bovine viral diarrhea virus
      (BVDV) in 10 Michigan dairy herds, it was calculated that screening of 5 young
      stock for BVDV antibody titer could be used to distinguish herds with
      persistently infected (PI) animals from herds without such animals. The herds
      were selected to represent 3 different herd categories: A, herds without use of
      vaccination and without PI animals (5 herds); B, herds with use of killed vaccine
      but no PI animals (2 herds); C, herds with use of killed vaccine and presence of
      PI animals (3 herds). The animals were described as having high antibody titers
      (> or = 128) or low antibody titers (< or = 64). For animals from 9 to 18 months
      of age, the probability of obtaining at least 3 animals with high titers among a
      screening sample of 5 animals was calculated as < 0.001 for all herds in category
      A, < 0.01 for the 2 herds in category B, and > 0.99 for all herds in category C.
      Thus, among herds in this study, by categorizing 9-18-month-old animals as having
      high titers (> or = 128) or low titers (< or = 64), herds with PI cattle could be
      distinguished from other herds by testing only 5 animals.

PMID- 7578447
TI  - Immunohistochemical and pathological study of Mycoplasma bovis-associated lung
      abscesses in calves.
AB  - Out of 45 cases of fatal chronic pneumonia in calves examined for Mycoplasma
      bovis infection from February to July 1994, 11 cases with pulmonary abscesses
      that were culture positive for M. bovis were encountered. The cases were studied
      in detail using a recently developed monoclonal antibody-based immunoperoxidase
      technique. Mycoplasma bovis organisms were detected in specific locations at all
      stages of abscessation observed. In bronchioles or terminal airways within which
      abscesses developed, M. bovis was located at the epithelial surface and in close
      association with infiltrating neutrophils and macrophages. Abscessed airways that
      had lost the epithelium were encapsulated and were seen as coagulative necrotic
      foci that stained intensely for M. bovis, especially at the periphery. Some foci
      stained weakly and such might have been resolving lesions. Mycoplasma bovis was
      also demonstrated at sites of mild mononuclear cell infiltration in the livers
      and kidneys of 2 calves. The mycoplasma was detected within bile ducts in the
      liver and in the tubular epithelium of the kidney. Abscesses not staining for M.
      bovis, presumably caused by other pathogens, were seen concurrently with M. bovis
      associated abscesses in some lungs. Thirteen other M. bovis-positive cases showed
      no abscesses, possibly indicating heterogeneity among M. bovis strains. Three
      other cases with abscesses were negative for M. bovis by culture and
      immunoperoxidase staining. The monoclonal antibody-based immunohistochemical
      technique is efficient for specific detection of M. bovis in cases of enzootic
      pneumonia of calves with or without abscessation. Mycoplasma bovis is implicated
      in the pathogenesis of lung abscesses in some calves.

PMID- 7578449
TI  - Apparent outbreaks of Clostridium difficile-associated diarrhea in horses in a
      veterinary medical teaching hospital.
AB  - Intestinal colonization with toxigenic strains of Clostridium difficile was
      documented in 9 of 10 horses with acute onset diarrhea in a veterinary medical
      teaching hospital, whereas a similar isolate was detected in only 1 of 23 other
      horses without diarrhea in the hospital. One horse with diarrhea was infected
      simultaneously with both C. difficile and Salmonella krefeld. Clostridium
      difficile was detected by fecal culture on selective medium, confirmed with a
      latex particle agglutination test, and identified as toxigenic by polymerase
      chain reaction amplification of toxin A and toxin B gene sequences. Using an
      arbitrarily-primed polymerase chain reaction, 6 distinct C. difficile isolates
      were detected in the feces of the 9 affected horses at the time of the outbreak
      of diarrhea.

PMID- 7578448
TI  - Colonization of the tracheal epithelium of pigs by filamentous bacteria
      resembling cilia-associated respiratory bacillus.
AB  - Warthin Starry staining revealed filamentous bacteria colonizing the tracheal
      epithelium of 41 of 88 (46.6%) pigs submitted for necropsy at 2 midwestern
      veterinary diagnostic laboratories. The bacteria were interspersed between and
      oriented parallel to the cilia. In 4 of 4 colonized pig tracheas, filamentous
      bacteria were demonstrated by transmission electron microscopy. The bacteria were
      approximately the same length and diameter as cilia, and in areas of heavy
      colonization the bacteria outnumbered cilia. The filamentous bacteria were
      similar in location and morphologic characteristics to cilia-associated
      respiratory (CAR) bacilli of rats, mice, rabbits, and cattle. Results of
      immunoperoxidase staining and polymerase chain reaction analysis indicated that
      the pig CAR bacillus is a different bacterium than the rat CAR bacillus. Rat CAR
      bacillus causes chronic respiratory disease in rats and mice. The association, if
      any, between pig CAR bacillus and swine respiratory disease is unknown.

PMID- 7578450
TI  - Evaluation of an enzyme-linked immunosorbent assay licensed by the USDA for use
      in cattle for diagnosis of ovine paratuberculosis.
AB  - A commercially available Mycobacterium phlei-absorbed enzyme-linked immunosorbent
      assay (ELISA) approved to detect antibodies to Mycobacterium paratuberculosis in
      cattle was evaluated for its applicability in sheep. The potential for
      interference with ELISA results from cross-reacting antibodies to Corynebacterium
      pseudotuberculosis was also investigated. Serum samples were randomly selected
      from a collection of samples obtained in 1986-1991 from 6 infected and 5
      noninfected sheep flocks varying in breed, age, and geographic origin. Tests were
      performed on sera from 27 paratuberculous sheep, confirmed by histopathology,
      bacteriologic culture, and/or acid-fast staining of ileal mucosal smears, and on
      sera from 246 noninfected sheep. The optical density of each sample was expressed
      as a percentage of the optical density of a known positive sheep serum sample
      tested on the same plate. These values were log-transformed to achieve normality
      of distribution, and sensitivity and specificity estimates were calculated based
      on 2 and 3 standard deviations above the mean of the percent positive value (PPV)
      of the noninfected sheep. A cutoff value of PPV > or = 55.74 resulted in an
      estimated sensitivity of 0.48 and a specificity of 0.95. Sera from 10 noninfected
      sheep with PPV above the cutoff level of 55.74% were absorbed with heat-treated
      C. pseudotuberculosis organisms in addition to M. phlei antigens. Sera from 14
      ELISA-positive paratuberculous sheep and 23 ELISA-negative noninfected sheep were
      similarly treated, and results were compared. Absorption with C.
      pseudotuberculosis resulted in a significant decrease in PPV in all 3 groups of
      sheep sera, but a greater decrease was observed in the noninfected sheep with PPV
      above the cutoff level when compared with noninfected sheep with PPV below that
      level. Results of this study suggest that ELISA may be of value in screening
      sheep flocks for paratuberculosis, but further experimentation is needed to
      optimize the sensitivity and specificity of the assay. Exposure to C.
      pseudotuberculosis may confound results obtained by M. phlei-absorbed ELISA for
      paratuberculosis.

PMID- 7578451
TI  - An enzyme-linked immunosorbent assay (ELISA) for serological diagnosis of
      Neospora sp. infection in cattle.
AB  - A kinetic enzyme-linked immunosorbent assay (ELISA) was developed and optimized
      for detection of antibodies to Neospora sp. in cattle. Sonicated tachyzoites of
      Neospora sp. isolated from an aborted bovine fetus were used as antigen.
      Variability in immunoblot patterns among positive sera, and the fact that all
      life stages of the parasites are unknown, justified use of a multiple-antigen
      ELISA to allow for maximum sensitivity. Immunoblot analysis revealed negligible
      cross-reactions between Toxoplasma gondii antigen and Neospora sp. antisera and
      between Neospora sp. antigen and antisera from various apicomplexan parasites.
      The maximum positive-to-negative Vmax (average maximum slope of the optical
      density over time) ratio was obtained using 200 ng/well of sonicated tachyzoite
      antigen and a 1:200 serum dilution. Using logistic regression to determine the
      optimal cutoff point between known infected and noninfected cattle, a sample-to
      positive control Vmax ratio of 0.45 was found to maximize the percent correct
      classification, with an estimated sensitivity of 88.6% and specificity of 96.5%.
      Use of Neospora caninum antigen following the same protocol demonstrated no
      difference in ELISA interpretation. Comparison with an existing indirect
      immunofluorescent antibody (IFA) test showed the ELISA to be the more sensitive
      and specific test for serodiagnosis of Neospora infection in cattle.

PMID- 7578452
TI  - The occurrence of mast cell tumors in young Shar-Peis.
AB  - During 1991 and 1992, 802 case submissions diagnosed as canine mast cell tumors
      were submitted to the Athens Veterinary Diagnostic Laboratory. Eighteen of these
      submissions were from dogs of the Shar-Pei breed. Of these 18 cases, 5 occurred
      in Shar-Peis less than 2 years of age, 4 of these were poorly differentiated, and
      4 out of 5 occurred in the inguinal or preputial area. Three mast cell tumors
      (grade I) occurred in Boxer/Boxer cross dogs, and 2 tumors (grade II) occurred in
      Cocker Spaniels younger than 2 years of age. Of the 23,315 histopathology
      submissions, only 164 were from Shar-Peis and 57 of these dogs were under 2 years
      of age.

PMID- 7578453
TI  - Pathology of experimentally induced chronic selenosis (alkali disease) in
      yearling cattle.
AB  - Prolonged oral exposure of cattle to elevated dietary selenium (Se) in forage and
      seleniferous plants in seleniferous areas of the western United States is
      associated historically with 2 clinical syndromes: alkali disease and "blind
      staggers." The potential for Se-induced disease in cattle and other species is
      considerable in areas with seleniferous shales, Se-accumulating plants, arid
      climates, and alkaline soils. These 2 Se-associated conditions were defined in
      the 1930s and 1940s, and the nosology of blind staggers is questionable.
      Seventeen yearling steers fed 0.15, 0.28, and 0.8 mg Se/kg body weight as
      selenomethionine or selenite for 120 days were euthanized and examined
      postmortem. Significant lesions were confined to 4 steers in the medium- and high
      dose selenomethionine group and to 1 steer in the high-dose selenite group.
      Grossly, dystrophic hoof lesions developed in 2 steers, 1 of which had extensive
      separation of horn from lamellar and coronary epidermis and also lost hair from
      the tail switch. Histologically, tubules in the stratum medium of hooves from
      these 5 steers were replaced by islands of parakeratotic cellular debris,
      separated by more normal hoof matrix. Two of the 5 steers also had hyperplasia,
      acanthosis, parakeratosis, and disorganized germinal epithelium of varying
      severity in hoof epithelium, particularly at the tips of epidermal lamellae.
      These changes may distinguish the hoof lesions of chronic selenosis from those of
      chronic laminitis in cattle, in which dermal (chorial) changes predominate. In
      skin from the distal part of the tail of the animal that lost its switch, most
      follicles were atrophic and devoid of hairshafts and displayed dyskeratosis and
      mild superficial follicular keratosis. No significant lesions developed in
      tissues other than integument. Autometallographic staining for catalytic Se bonds
      in various tissues, including skin, liver, and kidney, revealed no positive
      staining of hair shafts; the correlation between stain intensity and dose group
      was poor. These findings indicate that dietary exposure for 4 months to 0.28 and
      0.8 mg Se/kg in the form of selenomethionine and to 0.8 mg Se/kg in the form of
      sodium selenite reproduces in some cattle mild (subclinical) to severe (clinical)
      forms of alkali disease. No significant neurological, renal, or hepatic lesions
      developed, supporting the contention that blind staggers is caused by factors
      other than excessive dietary selenium.

PMID- 7578454
TI  - Influence of the antibiotics lincomycin and tylosin on aflatoxicosis when added
      to aflatoxin-contaminated diets of growing swine.
AB  - Effects of dietary aflatoxin (AF) and the antibiotics lincomycin (L) and tylosin
      (T) were evaluated in growing crossbred pigs. Six barrows (3 replicates of 2
      each, mean body weight 14.0 kg) per group were assigned to 1 of 6 treatment
      groups (for a total of 36): 0 mg L, 0 mg T, and 0 mg AF/kg of feed (control); 220
      mg L/kg of feed (200 g/ton); 110 mg T/kg of feed (100 g/ton); 2.5 mg AF/kg of
      feed; 2.5 mg AF plus 220 mg L/kg of feed; 2.5 mg AF plus 110 mg T/kg of feed.
      Barrows were administered their respective diets for 28 days. Body weight, body
      weight gain, and feed consumption were reduced by the AF alone, the AF plus L,
      and the AF plus T treatments, compared with control, L, and T treatments. Altered
      serum biochemical or hematologic measurements induced by AF treatments included
      increased serum activities of alkaline phosphatase and gamma-glutamyltransferase,
      increased hematocrit, hemoglobin, RBC count, WBC count, and mean cell hemoglobin,
      decreased serum concentrations of albumin, cholesterol, inorganic phosphorus,
      unsaturated iron binding capacity, total protein, and urea nitrogen, and
      decreased lymphoblastogenic response. Liver weight was increased, and microscopic
      lesions were consistent with those observed in cases of aflatoxicosis. With some
      other minor exceptions for hematologic and immunologic variables, these data
      indicate that the feed antibiotics lincomycin and tylosin, when added to
      aflatoxin-contaminated diets, do not have beneficial or detrimental effects on
      aflatoxicosis in growing swine.

PMID- 7578456
TI  - Failure to consider the antigenic diversity of porcine reproductive and
      respiratory syndrome (PRRS) virus isolates may lead to misdiagnosis.

PMID- 7578455
TI  - Hemostatic indices in healthy foals from birth to one month of age.
AB  - Hemostatic indices were determined in 45 healthy light breed foals, from birth to
      1 month of age, and in 20 healthy adult (> 2 years of age) light breed horses.
      Blood samples were obtained from each foal at 4 ages: 1) < 24 hours, 2) 4-7 days,
      3) 10-14 days, and 4) 25-30 days. The following hemostatic indices were
      determined: platelet count; prothrombin and activated partial thromboplastin
      times; activity concentrations of protein C, antithrombin III, plasminogen, alpha
      2 antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor
      1; plasma protein C antigen and fibrinogen concentrations; and serum fibrin
      degradation products concentration. Prothrombin and activated partial
      thromboplastin times were significantly longer at birth than in older foals. The
      plasma concentrations of the following were significantly lower at birth than in
      older foals: antithrombin III, plasminogen and tissue plasminogen activator
      activities, protein C antigen, and fibrinogen. Concentrations of the following
      were significantly higher at birth than in older foals: protein C and plasminogen
      activator inhibitor-1 activities and fibrin degradation products. These results
      indicate that hemostatic indices of neonatal foals differ significantly from
      those of older foals and adults. With the exceptions of antithrombin III and
      tissue plasminogen activator activities, all hemostatic indices measured in foals
      at 1 month of age were equivalent to adult values.

PMID- 7578458
TI  - Low prevalence of antibodies to bluetongue and epizootic hemorrhagic disease
      viruses in dogs from southern Georgia.

PMID- 7578457
TI  - Application of PCR for specific identification of epizootic hemorrhagic disease
      virus serotype 2.

PMID- 7578459
TI  - Effect of cytopathic bovine viral diarrhea virus (BVDV) superinfection on viral
      antigen association with platelets, viremia, and specific antibody levels in two
      heifers persistently infected with noncytopathic BVDV.

PMID- 7578460
TI  - Disseminated chlamydial infection in antelope.

PMID- 7578461
TI  - Comparison of the Gimenez staining method and antigen detection ELISA with
      culture for detecting chlamydiae in birds.

PMID- 7578462
TI  - Bordetella avium phase-shift markers: characterization of whole cell, cell
      envelope, and outer membrane proteins.

PMID- 7578463
TI  - Description of six new capsular types (29-34) of Streptococcus suis.

PMID- 7578466
TI  - Adrenal gland adenomas in raccoons (Procyon lotor) from the eastern United
      States.

PMID- 7578464
TI  - Fibrinohemorrhagic pneumonia in pigs naturally infected with Streptococcus suis.

PMID- 7578465
TI  - Tissue-invasive Tritrichomonas foetus in four aborted bovine fetuses.

PMID- 7578468
TI  - Acute salinomycin toxicosis of pigs.

PMID- 7578467
TI  - Serum vitamin A (retinol) reduction in broiler chicks on feed amended with
      Fusarium proliferatum culture material or fumonisin B1 and moniliformin.

PMID- 7578469
TI  - Dicoumarol (moldy sweet clover) toxicosis in a group of Holstein calves.

PMID- 7578470
TI  - Estimation of dynamic joint torques and trajectory formation from surface
      electromyography signals using a neural network model.
AB  - In this study, human arm movement was reconstructed from electromyography (EMG)
      signals using a forward dynamics model acquired by an artificial neural network
      within a modular architecture. Dynamic joint torques at the elbow and shoulder
      were estimated for movements in the horizontal plane from the surface EMG signals
      of 10 flexor and extensor muscles. Using only the initial conditions of the arm
      and the EMG time course as input, the network reliably reconstructed a variety of
      movement trajectories. The results demonstrate that posture maintenance and
      multijoint movements, entailing complex via-point specification and co
      contraction of muscles, can be accurately computed from multiple surface EMG
      signals. In addition to the model's empirical uses, such as calculation of arm
      stiffness during motion, it allows evaluation of hypothesized computational
      mechanisms of the central nervous system such as virtual trajectory control and
      optimal trajectory planning.

PMID- 7578471
TI  - Frequency-induced phase transitions in bimanual tapping.
AB  - The stability of bimanual performance of the frequency ratios 3:8 and 5:8 was
      examined from the perspective of the sine circle map and the associated Farey
      mode-locking hierarchy. By gradually increasing movement frequency, abrupt
      transitions from the initial frequency ratios to other frequency ratios were
      induced. In general, transitions occurred to frequency ratios that were near the
      initial frequency ratio but lower in the Farey ordering, and, hence, of higher
      stability in the sine circle map. A fair percentage of these transitions were to
      unimodularly related ratios. The transition routes from 3:8 and 5:8 remained
      largely unaffected by extensive practice of the lower-order ratios 2:5 and 3:5.
      Collectively, these results suggest that (i) bimanual tapping occurs in a domain
      in which frequency-locked states either overlap or are located sufficiently close
      to each other to make stochastic switching possible (coupling parameter K > 1 or
      close to 1); (ii) the overall stability of these frequency-locked states
      decreases as movement frequency increases (due to a decrease in K); and,
      consequently, (iii) the probability of transitions to nearby frequency ratios
      increases as movement frequency increases, due to the differential stability of
      the frequency locks.

PMID- 7578472
TI  - Analysis of kinematic invariances of multijoint reaching movement.
AB  - There is a no unique relationship between the trajectory of the hand, represented
      in cartesian or extrinsic space, and its trajectory in joint angle or intrinsic
      space in the general condition of joint redundancy. The goal of this work is to
      analyze the relation between planning the trajectory of a multijoint movement in
      these two coordinate systems. We show that the cartesian trajectory can be
      planned based on the task parameters (target coordinates, etc.) prior to and
      independently of angular trajectories. Angular time profiles are calculated from
      the cartesian trajectory to serve as a basis for muscle control commands. A
      unified differential equation that allows planning trajectories in cartesian and
      angular spaces simultaneously is proposed. Due to joint redundancy, each
      cartesian trajectory corresponds to a family of angular trajectories which can
      account for the substantial variability of the latter. A set of strategies for
      multijoint motor control following from this model is considered; one of them
      coincides with the frog wiping reflex model and resolves the kinematic inverse
      problem without inversion. The model trajectories exhibit certain properties
      observed in human multijoint reaching movements such as movement equifinality,
      straight end-point paths, bell-shaped tangential velocity profiles, speed
      sensitive and speed-insensitive movement strategies, peculiarities of the
      response to double-step targets, and variations of angular trajectory without
      variations of the limb end-point trajectory in cartesian space. In humans, those
      properties are almost independent of limb configuration, target location,
      movement duration, and load. In the model, these properties are invariant to an
      affine transform of cartesian space. This implies that these properties are not a
      special goal of the motor control system but emerge from movement kinematics that
      reflect limb geometry, dynamics, and elementary principles of motor control used
      in planning. All the results are given analytically and, in order to compare the
      model with experimental results, by computer simulations.

PMID- 7578473
TI  - Evolution of biological regulation networks under complex environmental
      constraints.
AB  - This work investigates the influence of environmental inducers on the
      organization of cell regulation networks, using a connectionist approach. Protein
      interactions are modeled by an asymmetrical recurrent network, the units of which
      take continuous values. In contrast to classical models, we explicitly introduce
      a genome to encode the architecture of the system. This feature enables us to
      introduce an evolution model, in which a genetic algorithm that mimics the
      effects of evolution on proteins mutual interactions is used. We assume an
      efficient system to respond to persistent environmental stimuli, independently of
      their amplitude. Results are presented that show a structuration of the network
      with the emergence of specialized hierarchal structures. These structures seem to
      drive the system at the edge of chaos, so that it can present adapted responses
      to significant environmental changes.

PMID- 7578474
TI  - Generalized motor programs for rapid bimanual tasks: a two-level multiplicative
      rate model.
AB  - A model is proposed for the timing of rapid bimanual movements. It combines (a)
      the notion of a generalized motor program (GMP) with invariant relative timing,
      (b) the two-level concept of timing control with a central level of control and a
      peripheral level where the observations are made, and (c) the hypothesis that a
      single GMP simultaneously controls both limbs. Our method is based on the
      analysis of temporal intervals measured among landmarks taken from the bimanual
      kinematic traces. We show that sets of tetrad ratios--each composed of two pairs
      of covariances among four temporal intervals in the actions--should be equal to
      1.0 if the hypothesis is correct. In addition, we show that these tetrad ratios
      should deviate systematically from 1.0 under certain, biologically realizable
      violations of the model. Data from human subjects show that the results generally
      conform to the basic model. Simulations are used to illustrate other violations
      of the model and to explore characteristics of the sampling distribution of the
      tetrad ratios under the model.

PMID- 7578475
TI  - Electroencephalogram and visual evoked potential generation in a mathematical
      model of coupled cortical columns.
AB  - This study deals with neurophysiologically based models simulating electrical
      brain activity (i.e., the electroencephalogram or EEG, and evoked potentials or
      EPs). A previously developed lumped-parameter model of a single cortical column
      was implemented using a more accurate computational procedure. Anatomically
      acceptable values for the various model parameters were determined, and a multi
      dimensional exploration of the model parameter-space was conducted. It was found
      that the model could produce a large variety of EEG-like waveforms and rhythms.
      Coupling two models, with delays in the interconnections to simulate the synaptic
      connections within and between cortical areas, made it possible to replicate the
      spatial distribution of alpha and beta activity. EPs were simulated by presenting
      pulses to the input of the coupled models. In general, the responses were more
      realistic than those produced using a single model. Our simulations also suggest
      that the scalp-recorded EP is at least partially due to a phase reordering of the
      ongoing activity.

PMID- 7578477
TI  - Self-organization of the velocity selectivity of a directionally selective neural
      network.
AB  - We first present a mathematical analysis of the relation between the parameters
      and the behavior of the basic module in the proposed neural network model for
      visual motion detection. Based on the analytical results, a learning rule is put
      forth that can develop velocity selectivity of directionally selective cells in
      the basic module. The learning rule is furthermore introduced into the total
      model called a 'mass model', which is constructed with many basic modules.
      Numerical simulation results showed that each basic module in the mass model
      learned in a self-organizing manner to acquire selectivity for the velocity of an
      input stimulus. The proposed learning rule would be plausible in the actual
      nervous system in that it is simple and can be described with only local
      information.

PMID- 7578478
TI  - Fundamental patterns of bilateral muscle activity in human locomotion.
AB  - Human gait is characterized by smooth, regular and repeating movements but the
      control system is complex: there are many more actuators (i.e. muscles) than
      degrees of freedom in the system. Statistical pattern-recognition techniques have
      been applied to examine muscle activity signals, but these have all concentrated
      exclusively on unilateral gait. We report here the application of factor analysis
      to the electromyographic patterns of 16 muscles (eight bilateral pairs) in ten
      normal subjects. Consistent with our prior work, we have established two factors,
      named loading response and propulsion, which correspond with important phases in
      the gait cycle. In addition, we have also discovered a third factor, which we
      have named the coordinating factor, that maintains the phase shift between the
      left and right sides. These findings suggest that the central nervous system
      solves the problem of high dimensionality by generating a few fundamental signals
      which control the major muscle groups in both legs.

PMID- 7578476
TI  - Bistability in cerebellar Purkinje cell dendrites modelled with high-threshold
      calcium and delayed-rectifier potassium channels.
AB  - Phase-plane analysis of the ionic currents underlying dendritic plateau
      potentials was carried out to study the nonlinear dynamics and steady-state
      transfer properties of the dendritic tree in cerebellar Purkinje cells. The
      results of an analysis of the P-type calcium and delayed rectifier potassium
      channel system are presented in this study. These channels constitute a simple
      system that can support bistability and plateau potentials. By requiring both the
      steady-state current-voltage curve and nullclines to mimic basic plateau
      potential properties, we obtained well-defined ranges of specific conductance
      that can support bistability. Hysteresis was found to be surprisingly prevalent
      in this simple ion-channel system. Using the steady-state current voltage
      relationship, we derive concise, algebraic expressions for the voltage and
      current thresholds of state transitions as functions of specific conductance. The
      significance of bistability in this ion-channel system is discussed with respect
      to the generation of plateau potentials in Purkinje cells dendrites and the role
      of the cerebellum in motor control.

PMID- 7578479
TI  - Nonlinear neuronal mode analysis of action potential encoding in the cockroach
      tactile spine neuron.
AB  - Neuronal mode analysis is a recently developed technique for modelling the
      behavior of nonlinear systems whose outputs consist of action potentials. The
      system is modelled as a set of parallel linear filters, or modes, which feed into
      a multi-input threshold. The characteristics of the principal modes and the multi
      input threshold device can be derived from Laguerre function expansions of the
      computed first- and second-order Volterra kernels when the system is stimulated
      with a randomly varying input. Neuronal mode analysis was used to model the
      encoder properties of the cockroach tactile spine neuron, a nonlinear, rapidly
      adapting, sensory neuron with reliable behavior. The analysis found two principal
      modes, one rapid and excitatory, the other slower and inhibitory. The two modes
      have analogies to two of the pathways in a block-structured model of the encoder
      that was developed from previous physiological investigations of the neuron.
      These results support the block-structured model and offer a new approach to
      identifying the components responsible for the nonlinear dynamic properties of
      this neuronal encoder.

PMID- 7578480
TI  - On the comparison of Feller and Ornstein-Uhlenbeck models for neural activity.
AB  - Diffusion processes have been extensively used to describe membrane potential
      behavior. In this approach the interspike interval has a theoretical counterpart
      in the first-passage-time of the diffusion model employed. Since the mathematical
      complexity of the first-passage-time problem increases with attempts to make the
      models more realistic it seems useful to compare the features of different models
      in order to highlight their relative performance. In this paper we compare the
      Feller and Ornstein-Uhlenbeck models under three different criteria derived from
      the level of information available about their parameters. We conclude that the
      Feller model is preferable when complete knowledge of the characterizing
      parameters is assumed. On the other hand, when only limited information about the
      parameters is available, such as the mean firing time and the histogram shape, no
      advantage arises from using this more complex model.

PMID- 7578481
TI  - A neural model of basal ganglia-thalamocortical relations in normal and
      parkinsonian movement.
AB  - Anatomical, neurophysiological, and neurochemical evidence supports the notion of
      parallel basal ganglia-thalamocortical motor systems. We developed a neural
      network model for the functioning of these systems during normal and parkinsonian
      movement. Parkinson's disease (PD), which results predominantly from
      nigrostriatal pathway damage, is used as a window to examine basal ganglia
      function. Simulations of dopamine depletion produce motor impairments consistent
      with motor deficits observed in PD that suggest the basal ganglia play a role in
      motor initiation and execution, and sequencing of motor programs. Stereotaxic
      lesions in the model's globus pallidus and subthalamic nucleus suggest that these
      lesions, although reducing some PD symptoms, may constrain the repertoire of
      available movements. It is proposed that paradoxical observations of basal
      ganglia responses reported in the literature may result from regional functional
      neuronal specialization, and the non-uniform distributions of neurochemicals in
      the basal ganglia. It is hypothesized that dopamine depletion produces smaller
      than-normal pallidothalamic gating signals that prevent rescalability of these
      signals to control variable movement speed, and that in PD can produce smaller
      than-normal movement amplitudes.

PMID- 7578482
TI  - Fractal dimension of electroencephalographic time series and underlying brain
      processes.
AB  - Fractal dimension has been proposed as a useful measure for the characterization
      of electrophysiological time series. This paper investigates what the pointwise
      dimension of electroencephalographic (EEG) time series can reveal about
      underlying neuronal generators. The following theoretical assumptions concerning
      brain function were made (i) within the cortex, strongly coupled neural
      assemblies exist which oscillate at certain frequencies when they are active,
      (ii) several such assemblies can oscillate at a time, and (iii) activity flow
      between assemblies is minimal. If these assumptions are made, cortical activity
      can be considered as the weighted sum of a finite number of oscillations (plus
      noise). It is shown that the correlation dimension of finite time series
      generated by multiple oscillators increases monotonically with the number of
      oscillators. Furthermore, it is shown that a reliable estimate of the pointwise
      dimension of the raw EEG signal can be calculated from a time series as short as
      a few seconds. These results indicate that (i) The pointwise dimension of the EEG
      allows conclusions regarding the number of independently oscillating networks in
      the cortex, and (ii) a reliable estimate of the pointwise dimension of the EEG is
      possible on the basis of short raw signals.

PMID- 7578483
TI  - Nutritional Markers as predictors of survival in patients on CAPD.

PMID- 7578484
TI  - Effect of peritoneal dialysis prescription and peritoneal membrane transport
      characteristics on nutritional status.
AB  - These data suggest that dialysis dose is one of the major determinants of protein
      and energy intake in PD patients and that higher doses of dialysis tend to
      improve outcome. The data also suggest that with a long time on PD the peritoneal
      membrane probably has some underlying histological changes that preclude it from
      optimally responding to injury and may predispose it to irreversible damage. A
      possible early finding in this case is an increase in peritoneal transport in
      patients whose transport was initially stable. Peritoneal membrane transport
      properties are an important determinant of not only dialysis dose, but also
      nutritional status via both direct and indirect means. It is therefore important
      to identify the individual patient's peritoneal membrane transport
      characteristics. These transport characteristics may change over time. High
      transporters on CAPD represent a unique challenge. They have ultrafiltration
      problems and a tendency toward protein malnutrition presumably due to increased
      dialysate protein losses while on CAPD. One must consider that malnutrition in a
      rapid transporter may be due to the fact that the patient is on the wrong PD
      therapy. A change to NIPD may rectify some of the biochemical parameters, but
      these patients may not always improve. Reasons for this occasional lack of
      improvement are multifactorial, but emphasize our need to look at each patient as
      an individual and not focus only on laboratory parameters.

PMID- 7578485
TI  - Metabolic acidosis and uremia.

PMID- 7578487
TI  - The effect of KT/V(urea) on nitrogen appearance and appetite in peritoneal
      dialysis.

PMID- 7578486
TI  - Nutrition and dialysis adequacy.

PMID- 7578489
TI  - Bioelectrical impedance analysis and dual energy x-ray absorptiometry to monitor
      nutritional status.
AB  - There exists an imperative to monitor changes in body composition in all dialysis
      patients on a regular basis to avoid overt malnutrition. In this regard, the
      absolute measurement of the fat-free mass assessment may not be as crucial as the
      serial measurement of fat-free mass with the same modality. A significant
      difference in measured fat and fat-free mass should be expected if different
      techniques are employed. Therefore, when attempting to monitor patients over time
      or to assess the effects of changes in therapeutic regimens, a single methodology
      should be employed. Our data validate the use of BIA in the stable PD patient,
      indicating that BIA can predict the DXA results. Considering the ease with which
      BIA measurements can be obtained and the lack of dependency on operator
      interpretation, BIA is an ideal technique for use in the clinical setting. The
      applicability of this technique for use in monitoring longitudinal changes in
      body composition has, in fact, been well established (25, 30, 31). BIA appears to
      be an excellent method for routine fat-free mass measurement in dialysis
      patients. In as much as malnutrition continues to remain a significant problem in
      PD patients, measuring and monitoring body composition is strongly recommended.

PMID- 7578488
TI  - Prescription planning for peritoneal dialysis: a practice challenge.

PMID- 7578490
TI  - Malnutrition in peritoneal dialysis patients: etiologic factors and treatment
      options.
AB  - It is clear that malnutrition is common in chronic dialysis patients and is
      associated with increased morbidity and mortality. Evidence is accumulating that
      several measures can be taken to improve the nutritional status of these
      patients. An early start of dialysis, an increase in dialysis dose, the use of
      biocompatible membranes or dialysis solutions, and intensive nutritional
      counseling should be applied when necessary. If these measures fail, additional
      interventions, such as parenteral or enteral nutritional supplements, rhGH, and
      rhIGF-1, alone or in combination, should be tried.

PMID- 7578491
TI  - Intraperitoneal amino acids: a therapy whose time has come?
AB  - In regard to the question posed in the title of this review, the answer is mixed.
      IPN is possible today but only on a limited basis and at high cost with uncertain
      benefit. A 1.1% amino acid dialysis solution for IPAA therapy is available in
      several European countries but has not yet been approved for use in the United
      States. When it becomes more widely available, IPAA should become an important
      tool, along with other types of therapy, for use in the maintenance of good
      nutritional status in PD patients.

PMID- 7578492
TI  - What is our impact?

PMID- 7578493
TI  - Treatment of peritonitis: how are we doing?

PMID- 7578495
TI  - What is the ideal technique for testing the biocompatibility of peritoneal
      dialysis solutions?

PMID- 7578496
TI  - Growth hormone and malnutrition in dialysis patients.
AB  - OBJECTIVE: To review the normal function of the growth hormone (GH) insulin-like
      growth factor (IGF) axis, how it is altered in end-stage renal failure, how this
      may contribute to malnutrition in dialysis patients, and how therapy with
      recombinant human growth hormone (rHuGH) and recombinant human IGF-I (rHuIGF-1)
      might be used to treat malnutrition in these patients. DATA SOURCES: Studies in
      the literature dealing with the GH-IGF endocrine axis and its role in uremic
      malnutrition. STUDY SELECTION: Eight studies in which uremic adults were treated
      with either rHuGH or rHuIGF-I. DATA EXTRACTION: Data were abstracted from all of
      these studies. RESULTS: The review shows that there are marked abnormalities of
      the GH-IGF axis in uremic patients and that these lead to a state of GH
      resistance, which can be overcome by pharmacological doses of rHuGH. A small
      number of clinical studies in uremic adults suggests that both rHuGH and rHuIGF-I
      have dramatic beneficial effects on nutritional status in these patients.
      CONCLUSIONS: rHuGH and rHuIGF-I have both been shown to have a beneficial effect
      on nutritional status in short-term studies on small numbers of patients. Further
      studies need to be done for longer periods in larger groups of patients. Areas
      for additional research are suggested.

PMID- 7578494
TI  - Is lymphatic absorption important for ultrafiltration?

PMID- 7578497
TI  - Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD.
AB  - OBJECTIVE: To investigate whether dialysate concentrations of substances that are
      locally produced within the peritoneal cavity can be used to study the effects of
      inflammation on peritoneal tissue. DESIGN: We followed the appearance rates (AR)
      of concentrations of cancer antigen (CA) 125, phospholipids (PHL), hyaluronan
      (HA), and the procollagen peptides PICP (procollagen 1 C-terminal) and PIIINP
      (procollagen 3 N-terminal) in dialysate during peritonitis (8 consecutive days)
      and after recovery. Data were compared with the stable situation. SETTING: CAPD
      (continuous ambulatory peritoneal dialysis) unit in the Academic Medical Center
      in Amsterdam. PATIENTS: Twelve CAPD patients with a total of 16 episodes of
      peritonitis and 10 clinically stable CAPD patients were studied. RESULTS: All
      substances showed temporal increments in dialysate during peritonitis compared to
      control. No difference was found between the control day of peritonitis and the
      stable patients. Maximum AR were reached in the acute phase of peritonitis for
      CA125, PHL, and HA and on day 4 for both PICP and PIIINP. A second increment in
      CA125 occurred on days 4 to 6. These findings indicate acute damage to the
      mesothelium (CA125) and other cells (PHL) by the infection. HA may reflect
      stromal changes. Subsequently, peritoneal healing (PICP,PIIINP) and
      remesothelialization (second peak CA125) are likely to occur. CONCLUSIONS:
      Dialysate concentrations of these substances can be used as markers for the
      effects of peritonitis on the peritoneum of CAPD patients in vivo. The similarity
      between the marker concentrations in the effluent after recovery from peritonitis
      and those in stable CAPD patients implies that complete peritoneal healing is
      likely to occur after uncomplicated peritonitis.

PMID- 7578498
TI  - Peritonitis occurrence in a multicenter study of icodextrin and glucose in CAPD.
      MIDAS Study Group. Multicenter Investigation of Icodextrin in Ambulatory
      Dialysis.
AB  - OBJECTIVE: To compare peritonitis occurrence and outcome in a large U.K. study
      Multicentre Investigation of Icodextrin in Ambulatory Dialysis (MIDAS). DESIGN:
      Prospective, randomized, controlled 6-month comparison of icodextrin with glucose
      for the long dwell in continuous ambulatory peritoneal dialysis (CAPD) patients.
      SETTING: Eleven CAPD units in U.K. teaching hospital. PATIENTS: A total of 209
      patients established on CAPD for at least 3 months (103 control, 106 icodextrin).
      Twenty-three control (C) and 22 icodextrin (I) patients experienced peritonitis
      during the study. INTERVENTION: Patients who had peritonitis remained on
      treatment (unless CAPD was withdrawn, temporarily or permanently). MAIN OUTCOME
      MEASURES: The main outcome measures were the rate of peritonitis and duration of
      CAPD treatment prestudy; the rate of peritonitis episodes and their outcome
      during study; the effect of peritonitis on laboratory variables, serum icodextrin
      metabolites, and ultrafiltration efficacy. RESULTS: Prestudy: Nine (39%) of C but
      14 (64%) of I patients had suffered previous peritonitis episode(s), with overall
      rates of 0.58 and 0.78 episodes per patient-year, respectively. DURING STUDY:
      There were 31 C episodes and 35 I episodes, with overall rates of 0.76 and 0.93
      per patient-year, respectively. The increase in the C and I groups was 31% and
      19%, respectively. Serum osmolality and sodium levels were unaffected by
      peritonitis, and there was no increase in serum icodextrin metabolites during
      peritonitis. Overnight ultrafiltration volume during peritonitis (mean +/- SD)
      declined slightly from 218 +/- 354 mL to 185 +/- 299 mL (NS) in the control
      group, but increased in the icodextrin group from 570 +/- 146 mL to 723 +/- 218
      mL (p < 0.01). CONCLUSIONS: Using icodextrin for the long dwell in CAPD does not
      increase the rate of peritonitis, nor does it alter the outcome of peritonitis.
      Peritonitis does not affect uptake of icodextrin from the peritoneum.

PMID- 7578499
TI  - Increased response to subcutaneous erythropoietin on type I diabetic patients on
      CAPD: is there a synergistic effect with insulin?
AB  - OBJECTIVE: To evaluate the effect of subcutaneous erythropoietin (SC EPO) on the
      treatment of anemia in diabetic and nondiabetic continuous ambulatory peritoneal
      dialysis (CAPD) patients. DESIGN: A resistance index was designed for measuring
      the relative EPO response, dividing EPO dose (U/kg/week) by the hemoglobin (Hb)
      increment with respect to the basal level. PATIENTS: Eleven nonselected type I
      diabetic patients using subcutaneous insulin compared with 16 nondiabetic
      controls, all on CAPD therapy. RESULTS: The two groups showed similar mean
      baseline hemoglobin levels (7.4 D-I and 7.7 non-D, g/dL). There was a
      statistically significant lower resistance index for diabetics (13.8 +/- 9.7
      U/kg/g Hb increment) compared to nondiabetic (55.8 +/- 128, p < 0.001).
      Multivariate analysis confirmed an independent association between diabetes and
      resistance index. The response to EPO was slightly better among those diabetic
      patients with lower levels of serum parathyroid hormone (iPTH) (PTH-resistance
      index, correlation coefficient, r = 0.7, p < 0.05). No other differences, apart
      from the use of subcutaneous insulin, were found between diabetics and controls.
      Although diabetic patients had an increased response to EPO, they had no more
      frequent side effects than nondiabetics. CONCLUSIONS: According to our results,
      we suggest that factors related to insulin-dependent diabetes seem to be involved
      in a favorable response to SC EPO. Hyperinsulinemia derived from subcutaneous use
      of insulin might act as a comitogen with the induced increments of serum
      erythropoietin.

PMID- 7578501
TI  - Comparison of three different tests for assessment of hepatitis C virus in
      dialysis patients.
AB  - OBJECTIVE: To evaluate the relationship between hepatitis C virus antibodies (HCV
      Ab) and viremia and to compare the prevalence of HCV-Ab and HCV viremia in
      hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients.
      DESIGN: Cross-sectional study. SETTING: Dialysis unit of a nephrology division in
      a public university hospital. PATIENTS: All dialysis patients who came for
      routine clinic visits during the study period. None denied informed consent.
      Forty-eight patients on HD and 79 on CAPD were examined. INTERVENTION: Blood
      samples were tested by second-generation enzyme-linked immunosorbent assay (ELISA
      II) and recombinant immunoblot assay (RIBA II) to look for HCV-Ab and by the
      polymerase chain reaction (PCR) to look for HCV viremia. RESULTS: ELISA II was
      positive in 52% of HD patients and in 14% of CAPD patients. RIBA II was positive
      in 48% of HD patients and in 11% of CAPD patients. HCV viremia was positive by
      PCR in 41.6% of HD patients and in 12% of CAPD patients. Two of these PCR
      positive patients did not show HCV-Ab by ELISA II and RIBA II. The sensitivity
      and specificity of ELISA II were 93% and 92%, the sensitivity and specificity of
      RIBA II were 86% and 94%. CONCLUSIONS: Our data confirm a higher prevalence of
      HCV viremia in HD than in CAPD patients. The absence of Ab against virus C in 2
      patients positive with PCR might be due to recent HCV infection or to weak virus
      replication or to a poor immune response.

PMID- 7578500
TI  - Continuous ambulatory peritoneal dialysis in end-stage renal disease due to
      multiple myeloma.
AB  - OBJECTIVE: To evaluate (1) the disease course, (2) the response to recombinant
      human erythropoietin (rHuEPO), and (3) the morbidity and mortality of patients
      with end-stage renal disease (ESRD) due to multiple myeloma (MM) who were treated
      with continuous ambulatory peritoneal dialysis (CAPD) DESIGN: Retrospective
      study. SETTING: Tertiary teaching hospital--The Toronto Hospital, Toronto,
      Ontario, Canada. PATIENTS: Seven patients with ESRD due to MM who were treated
      with CAPD. RESULTS: Mean age of the patients was 77.2 years (median 80 years,
      range 65-88 years). Two were in stage IB, 1 was in stage IIB, and the remaining 4
      were in stage IIIB, according to Durie and Salmon's staging. Three patients
      received rHuEPO; 2 of these also were receiving chemotherapy for myeloma. The
      mean rHuEPO requirement was 277 U/kg/wk, which was more than other ESRD patients'
      requirements. Mean duration of CAPD was 20.6 months (6-58 months). The
      peritonitis rate was one episode in 14.4 months. The frequency of hospitalization
      was once in 5.6 months, and the mean number of days spent in hospital was 20 days
      per year. Quality of life did not get worse and, if anything, improved marginally
      while they were on CAPD. Three patients died after a mean survival of 32.7
      months, and the remaining 4 patients are still alive. CONCLUSIONS: Myeloma
      patients with ESRD do fairly well on CAPD without deterioration in their quality
      of life and with an acceptable peritonitis rate.

PMID- 7578502
TI  - Correlations between plasminogen activator inhibitor-1 and peritoneal transport
      in pediatric CCPD patients.
AB  - OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of
      plasminogen activators and has been shown to be involved in the accumulation of
      extracellular matrix (ECM) in various tissues. Since peritoneal ECM is a
      resistance site for peritoneal transport, the production and release of PAI-1 in
      the peritoneum may affect the peritoneal transport of water and small solutes.
      DESIGN: The linear correlations between the dialysate PAI-1 levels and the
      variables of peritoneal transport during peritoneal equilibration tests (PET)
      were examined. SETTING: A tertiary university hospital. PATIENTS: Six stable
      pediatric patients (age 10.8 +/- 4 years) undergoing continuous cycler-assisted
      peritoneal dialysis were included. INTERVENTIONS: None. RESULTS: All data are
      mean +/- SD. There was a positive correlation between the infused volume and the
      net ultrafiltration (UF, 198 +/- 127 mL, r = 0.82, p < 0.05). The dialysate PAI-1
      levels increased during the dwell time (2.44 +/- 2.23 ng/mL or 2.46 +/- 1.72
      micrograms at 4 hours vs 0.04 +/- 0.1 ng/mL or 0.04 +/- 0.09 micrograms at 0
      hour, p < 0.05). The saturation indices (dialysate/plasma ratio) of PAI-1 and
      albumin at 4 hours were 1.05 +/- 1.21 and 0.028 +/- 0.004, respectively. The
      changes from 0 hour dwell to 4 hour dwell in the dialysate PAI-1 concentration
      (PAI4-0, 2.4 +/- 2.2 ng/mL) or amount corrected to body surface area (APAI4
      0/BSA, 2.61 +/- 2.11 micrograms/m2) negatively correlated with UF or UF/body
      surface area and positively correlated with the number of episodes of
      peritonitis. There was no correlation between PAI4-0,APAI4-0/BSA, or plasma PAI-1
      concentration and the mass transfer coefficient and clearance of either urea or
      creatinine. CONCLUSIONS: The elevated PAI-1 level during the PET was likely from
      the local production and release of PAI-1. It had an inverse relationship with
      the amount of ultrafiltration. Repeated inflammation of the peritoneum was
      associated with an increased production and release of PAI-1 into the peritoneum.

PMID- 7578503
TI  - A usual peritoneal dialysis patient with an unusual skin disease.

PMID- 7578504
TI  - Urea kinetics and nitrogen appearance rates in diabetic patients on peritoneal
      dialysis.
AB  - OBJECTIVE: We compared the relationship of protein intake (as measured by protein
      nitrogen appearance) and dialysis delivery in insulin-dependent diabetic (IDDM)
      and nondiabetic patients. DESIGN: One to two 24-hour dialysate and urine
      collections were obtained in 20 diabetic patients and 42 nondiabetic patients.
      The protein equivalent of nitrogen appearance (PNA) was calculated by the
      Randerson formula. KT/V was determined using V obtained by the Watson formula.
      PNA was normalized using three different methods to determine body weight: first,
      by normal or ideal body weight according to the Metropolitan Table (nPNA);
      second, by standard body weight according to the NHANES Table (sPNA); and third,
      by V/0.58 (vPNA). RESULTS: The mean PNA was not different in diabetics and
      nondiabetics (53 +/- 21 g/day vs 60 +/- 14 g/day), nor was weekly KT/V (2.1 +/-
      0.6 vs 2.1 +/- 0.6). Mean normalized PNA was not different in IDDM versus non-DM
      regardless of the method. KT/V correlated with nPNA in IDDM (r = 0.54, p = 0.002
      and non-DM, r = 0.31, p = 0.03), and with vPNA in IDDM (r = 0.73, p < 0.00001,
      and non-DM, r = 0.45, p = 0.0009). KT/V also correlated with sPNA in IDDM (r =
      0.57, p = 0.001), but not in non-DM (r = 0.25, p = 0.08). The slope for
      normalized PNA versus KT/V was steeper for IDDM than for non-DM. CONCLUSION: KT/V
      and PNA are more closely correlated in IDDM patients than in non-DM patients.
      Thus it is extremely important that IDDM patients receive an adequate level of
      dialysis.

PMID- 7578505
TI  - Outcome of pancreatitis in CAPD and HD patients.

PMID- 7578506
TI  - Thyroid hormone losses in CAPD.

PMID- 7578507
TI  - Effectiveness of once-weekly vancomycin and once-daily gentamicin,
      intraperitoneally, for CAPD peritonitis.

PMID- 7578508
TI  - The peritoneal equilibration test cannot predict the mass transfer area
      coefficients.

PMID- 7578509
TI  - A positive correlation of PCRN to KT/V in cross-sectional studies is not proof of
      a causal relationship.

PMID- 7578510
TI  - Predisposing and prognostic factors of fungal peritonitis in peritoneal dialysis.

PMID- 7578511
TI  - Inflow obstruction due to kinking of coiled catheters during placement.

PMID- 7578512
TI  - Reversible catheter obstruction by omental wrapping in a CAPD patient.

PMID- 7578513
TI  - Interleukin, endotoxin, and tumor necrosis factor in CAPD dialysate.

PMID- 7578514
TI  - Symptomatic peripheral eosinophilia associated with peritoneal eosinophilia in a
      CAPD patient.

PMID- 7578515
TI  - Effect of hematocrit on D/P ratio in peritoneal dialysis.

PMID- 7578516
TI  - Constipation occurs less frequently in CAPD patients than in HD patients.

PMID- 7578517
TI  - Intraperitoneal antibiotics effectively treat non-dialysis-related infections.

PMID- 7578518
TI  - Body surface area and anthropometric body water in patients on CPD.

PMID- 7578519
TI  - Literature. April-June 1995.

PMID- 7578520
TI  - Kinetics of minimal residual disease during induction/consolidation therapy in
      standard-risk adult B-lineage acute lymphoblastic leukemia.
AB  - We have compared the kinetics of minimal residual disease (MRD) by simultaneous
      polymerase chain reaction (PCR) monitoring with oligonucleotides for the
      immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and
      the T-cell receptor gamma chain gene (TCR gamma), as well as clone-specific CDR3
      sequences in adult patients (aged 17-51 years) with acute lymphoblastic leukemia
      (ALL) who entered a complete hematological remission (CR) after chemotherapy with
      the German multicenter ALL (GMALL) protocol. The sensitivities were one in 10(2
      3) for the CDR3- and TCR gamma-PCR and one in 10(5-6) for a two-step, seminested
      CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four
      were TCR gamma positive in their bone marrow (BM). At the end of induction
      therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCR gamma, and 5/6
      for clone-specific rearrangements. At the end of consolidation treatment (after 7
      months) only 1/7 remained positive for CDR3, 2/7 for TCR gamma, and 5/7 for clone
      specific rearrangements. After an observation period of 18-36 months, 4/7
      patients were still in CR and all were PCR negative by the clone-specific method
      during or after maintenance therapy. Two patients died in leukemic relapse; one
      patient relapsed but is still alive. All three of these patients remained PCR
      positive throughout the course of their disease. Clonal evolution in the IgH
      locus was found in one of these patients. We conclude that the molecular response
      to chemotherapy in adult B-lineage ALL is slow, even in patients without risk
      factors other than age. As in childhood ALL, most patients with long-term CR
      convert to PCR negativity approximately 18 months after the start of
      chemotherapy. The data also suggest the existence of early clone-specific PCR
      negativity in a small proportion of long-term survivors. The predictive value of
      this observation will now have to be confirmed in a larger study.

PMID- 7578522
TI  - Autologous platelet transfusion in alloimmunized patients with acute leukemia.
AB  - Seventy-eight transfusions of autologous platelets were given to eight
      alloimmunized patients receiving curative chemotherapy for acute leukemia.
      Platelets were collected at regeneration of hematopoiesis after a chemotherapy
      cycle, cryopreserved with 5% dimethylsulfoxide in liquid nitrogen, and
      retransfused during bone marrow aplasia following the next treatment cycle. The
      in vitro platelet recovery after freezing, thawing, and washing was 85 +/- 4%.
      The in vivo corrected count increment 1 h after autologous platelet transfusions
      was 11 +/- 5 x 10(9)/l. With the exception of moderate urticaria and slight
      nausea each after one transfusion, no immediate or chronic side effects occurred.
      The bleeding time was shortened and hemorrhage during bone marrow aplasia was
      prevented in all alloimmunized patients by autologous platelet transfusions.

PMID- 7578521
TI  - Plasma levels of IL-1, TNF alpha, IL-6, IL-8, G-CSF, and IL1-RA during febrile
      neutropenia: results of a prospective study in patients undergoing chemotherapy
      for acute myelogenous leukemia.
AB  - Plasma levels of IL-1, IL-6, IL-8, IL1-RA, TNF alpha, and G-CSF were
      prospectively studied during 23 chemotherapy cycles of 20 patients suffering from
      acute myelogenous leukemia. Increased plasma levels of IL-6, IL-8, and G-CSF were
      observed in patients with febrile neutropenia and/or major infection. Plasma
      levels of IL-6, IL-1, TNF alpha and IL-1-RA measured 1 day before and 1 day after
      the onset of febrile episodes did not accurately predict the development of major
      infection. In contrast, IL-8 plasma levels were significantly higher in those
      patients who subsequently developed major infection. The question whether IL-8
      plasma levels identify high risk or low risk patients with sufficient specificity
      and sensitivity has to be answered in large scale clinical trials.

PMID- 7578525
TI  - Hemoglobin variants recently detected in Austria.
AB  - Measurement of glycated hemoglobin (HbAtc) is used for routine management of
      diabetic patients. Glucose linkage to HbAtc reflects mean blood glucose levels
      during the last 3 months before examination. Various methods for HbA1c
      determination show abnormal values with hemoglobin variants. In some diabetic
      patients excessively high HbA1c values with high-performance liquid
      chromatography (HPLC) led to the detection of Hb Graz. In addition to Hb Graz,
      other silent hemoglobin variants have been found in Austria. Here we review Hb
      Graz, Hb Sherwood Forest, and Hb Okayama detected while using HPLC for the
      measurement of HbA1c in diabetic patients.

PMID- 7578524
TI  - Acquired pure red cell aplasia: a study of six cases.
AB  - Persistent infection by parvovirus B19 associated with pure red cell aplasia
      (PRCA) has been documented in immunocompromised patients. Bone marrow failure is
      associated with conditions in which immune surveillance is impaired, and in these
      instances occult parvovirus infection may be suspected. In this study we have
      assessed by serological and molecular methods whether parvovirus B19 infection
      may be a more frequent cause of PRCA than hitherto suspected and whether it may
      be present in the absence of a typical bone marrow picture. Six patients with
      PRCA--two with isolated PRCA and no apparent underlying disease, two with a
      lymphoproliferative disease, one with thymoma, and one with chronic
      myelomonocytic leukemia--have been studied. Four of the six patients had overt
      PCRA and were clearly immunocompromised. Parvovirus B19 was not detected in any
      of the six patients by PCR analysis and serology investigating the presence of
      IgM or IgG antibodies. Although parvovirus B19 infection needs to be ruled out in
      PRCA it represents only one, and probably not the most frequent, etiological
      factor of PRCA.

PMID- 7578523
TI  - Low doses of rIL2 after autologous bone marrow transplantation induce a
      "prolonged" immunostimulation of NK compartment in high-grade non-Hodgkin's
      lymphomas.
AB  - Ten patients with high-grade non-Hodgkin's lymphoma (HG-NHL) entered a
      subcutaneous (s.c.) recombinant interleukin 2 (rIL2) trial within 2 months of
      undergoing autologous bone marrow transplantation (ABMT). Immunological studies,
      consisting in T- and natural killer (NK)-cell subset assessment, together with
      functional assays, such as NK activity and CD16-mediated redirected killing
      assay, were performed before therapy, after 2 weeks, and then monthly. Phenotypic
      analysis showed a significant increase (p = 0.01) of CD16 and CD56 NK cells, from
      12% to 28% and from 17% to 37%, respectively. In particular, the CD56bright NK
      cell population showed a tenfold increase, while CD56dim NK cells remained
      unmodified compared with pretreatment values. The expression of IL2 receptors was
      also studied and a significant increase (p = 0.01) of CD122 (p75)-positive cells
      from 8% to 30% was found, while no significant increase was observed in CD25
      (p55)-positive cells. Furthermore, rIL2 administration led to an increase of NK
      activity even at the lowest effectors:target ratio and to an increase of CD16
      mediated redirected killing assay. These phenotypic and functional modifications
      lasted throughout the duration of rIL2 therapy and remained after completion of
      therapy. In addition, none of the ten patients relapsed, and two of them who
      started IL2 treatment while still showing residual disease experienced a complete
      disappearance of the disease after 10 and 7 months of therapy, respectively. Our
      data suggest that infusion of rIL2 s.c. after ABMT is safe, can selectively
      increase NK cell number and function, and may have a beneficial effect on the
      minimal residual disease.

PMID- 7578526
TI  - Different organization of von Willebrand factor oligomers in type-2A and -2B von
      Willebrand disease variants: effects of DDAVP infusion and protease inhibitors.
AB  - Plasma von Willebrand factor (vWf) displays a complex pattern of repeating
      multimers, whose heterogeneous size distribution seems to depend on the
      proteolytic cleavage of the constituent vWf subunit. Smaller vWf multimers are
      thought to derive by proteolytic cleavage of the larger forms. To clarify the
      relationship between large multimer representation and the structure of small vWf
      oligomers, DDAVP was infused in patients with type-2A and -2B von Willebrand
      disease (vWd) variants which lack circulating high vWf forms. Before infusion,
      high-resolution multimer analysis demonstrated a more pronounced representation
      of the satellite bands of each oligomer, mainly concerning fast-moving
      components, especially in type 2B vWd. After DDAVP, in type-2A vWd each oligomer
      displayed a different organization depending on whether restoration of large vWf
      multimers occurred. The lack of large vWf multimer restoration, as shown in
      citrated samples, was associated with the fast band being significantly more
      represented than the slower, and almost similar to the central component. In
      contrast, when the high-molecular-weight vWf forms were restored, as occurred in
      the samples collected in the presence of protease inhibitors, the relative
      representation of the fast- and slow-moving bands was similar to that of normal
      samples. In type-2B vWd, regardless of the anticoagulant used, DDAVP infusion did
      not restore large vWf multimers, and each oligomer displayed a significant
      increase in both the central band and fast-moving satellite, the fast being even
      more highly represented. These findings suggest that, regardless of the origin,
      the disappearance of large circulating multimers in type-2A and -2B vWd induces
      an increased representation of the fast-moving satellite of the low-molecular
      weight multimers. Moreover, the time course of large and low/intermediate
      multimer decrease and increase provides a further demonstration that low vWf
      multimers derive from the larger ones, and that mainly the fast-moving band of
      the oligomer is involved.

PMID- 7578527
TI  - Anticardiolipin antibodies do not seem to be associated with APC resistance in
      vivo or in vitro.
AB  - Anticardiolipin antibodies (aCL) or lupus anticoagulants (LA) have been found to
      exert an inhibitory action upon the activation and function of protein C, a
      natural coagulation inhibitor. Recently an in vitro phenomenon called resistance
      to activated protein C (APC resistance) has been described as the most frequent
      cause of hereditary thrombophilia. In order to see whether a positive association
      of APC resistance with aCL exists we examined plasma of 162 consecutive
      outpatients referred for thrombophilia screening. Further, the IgG fraction was
      isolated from plasma of two aCL-positive and LA-negative patients and of two aCL
      negative healthy subjects by means of protein A affinity chromatography. Each of
      these isolates was mixed with normal plasma, and the APC resistance was assayed;
      25/162 (15.4%) patients had confirmed abnormal APC resistance. Only 1/25 (4.0%)
      APC resistance-positive patients and 11/137 (8.0%) APC resistance-negative
      patients had positive IgG- and/or IgM-aCL (p = 0.5, nonsignificant). In the in
      vitro test system the APC resistance ratio remained unaffected after addition of
      normal IgG or aCL-IgG fraction in the tested normal plasma and did not deviate
      from the range of buffer controls. These data do not suggest any association of
      aCL with abnormal APC resistance. aCL-IgG fractions from aCL-positive and LA
      negative plasmas do not interfere with the APC resistance test system in vitro in
      low concentration.

PMID- 7578529
TI  - Risks to health, risk management and environmental health impact assessment.

PMID- 7578528
TI  - Rapid elimination of a high-titer spontaneous factor V antibody by extracorporeal
      antibody-based immunoadsorption and immunosuppression.
AB  - We report on the rapid elimination of a potent spontaneous factor V antibody of
      undetermined etiology by extracorporeal immunoadsorption on sepharose-bound
      polyclonal sheep antibodies to human immunoglobulins (Ig-Therasorb, Baxter) in
      combination with immunosuppressive treatment. A 68-year-old woman presented with
      severe hematuria. Severe factor V deficiency (< 1%) caused by an antibody to
      factor V (26 BU/ml) was found. Extracorporeal immunoadsorption (8.245 +/- 553 ml
      plasma processed per session) led to an average reduction of the antibody titer
      by 75% per session. The procedure was well tolerated without any side effects.
      Hematuria ceased after three immunoadsorptions and complete elimination of the
      antibody was achieved after seven sessions (day 15), followed by a rapid increase
      of the factor V activity to normal levels. Treatment with cyclophosphamide and
      prednisone was started on day 6 and continued for 2 months. The patient remains
      in remission at 6 months. Extracorporeal immunoadsorption is a highly effective
      method for eliminating antibodies to factor V (or other clotting factors) in
      selected cases, i.e., in patients with severe bleeding tendency, high antibody
      titer, and low probability of a rapid spontaneous remission.

PMID- 7578530
TI  - Health outcomes, health promotion and improved public health in Australia.

PMID- 7578531
TI  - Tuberculosis, Australia and the global emergency.

PMID- 7578532
TI  - Efficiency in health care: just health gains?

PMID- 7578533
TI  - Cost-effectiveness of alternative interventions for the prevention and treatment
      of coronary heart disease.
AB  - Although mortality from coronary heart disease (CHD) in Australia has fallen
      dramatically since the 1960s, it still remains the major cause of death in
      Australia and poses a significant burden on the economy. Even though a number of
      studies have concluded that prevention has been the main determinant of the
      declines in CHD, a disproportionate amount of health-care expenditure is devoted
      to treatment rather than prevention. This paper reviews the international
      literature on the economic appraisal (costs and benefits) of alternative
      interventions for the treatment and prevention of CHD with the view of assessing
      whether there is sufficient evidence to justify a reallocation of resources away
      from treatment to prevention. First, few studies on the economic evaluation of
      CHD prevention and treatment programs have been undertaken in Australia, with
      most being from the United States and Europe. Second, assumptions about the
      specification, measurement and valuation of costs, and the epidemiological
      evidence on program effectiveness have varied. Third, health promotion and
      prevention programs are not necessarily more cost-effective than drug or surgical
      treatments for CHD. Individual interventions must be judged on their own merits.
      There is a need for a systematic evaluation of interventions for CHD using
      primary Australian data to better inform decision making on resource-allocation
      priorities. Such an evaluation should incorporate economic evaluation techniques.

PMID- 7578534
TI  - Assessment of the future impact on health of a proposed freeway development.
AB  - This paper estimates the effect on health of traffic injury and air and noise
      pollution from a proposed inner-suburban freeway in Melbourne. We estimated
      levels of these health problems for the year 2001 using traffic flow projections
      for the presence and absence of the freeway. For noise and air pollution, it was
      necessary to use pollutant levels as proxies for levels of associated diseases
      and health states. In 2001, there will be an increase in all traffic movements in
      the study area but a decrease of 100,000 vehicle-kilometers per day on major
      roads, excluding the bypass. This is associated with a projected reduction in the
      study area of about 100 to 110 injuries of all types. The major air pollution
      problems associated with motor vehicle emissions are ozone and respirable
      particulates; sulphur dioxide, nitrogen dioxide and carbon monoxide are unlikely
      to pose a health hazard. Levels of respirable particulates, lead and polycylic
      aromatic hydrocarbons are generally low. There should be no detectable increase
      in average or maximum noise levels adjacent to the freeway if attenuation
      measures are employed. A reduction in average and maximum noise levels should
      occur on some main roads in the affected area. The effects of the freeway on the
      area should be favourable to health, with reduction in traffic injury and noise
      related health problems outweighing any risk of a small deterioration in
      respiratory health associated with atmospheric pollution.

PMID- 7578535
TI  - Exposure to pesticides in ambient air.
AB  - Ambient air was monitored for pesticides at four sites in Coffs Harbour, a
      coastal town (population about 50,000) surrounded by banana plantations. Air was
      sampled continuously for five consecutive months during the peak agricultural
      spraying period using vacuum pumps set to sample one litre per minute through
      ORBO-42 absorption tubes. Six pesticides were detected: three organochlorines and
      three organophosphates. The most commonly detected pesticide (14 per cent of all
      samples) was chlorpyrifos (maximum detected level 208.0 ng/m3, mean 3.6 ng/m3).
      Heptachlor was detected in 7.1 per cent of all samples (maximum detected level
      133 ng/m3, mean 2.7 ng/m3). Other pesticides were only rarely detected. The only
      pesticide applied by air in the district (propiconazole) was not detected. If
      international health guidelines are used as a yardstick, these levels of exposure
      appear unlikely to present an appreciable health risk. Chlorpyrifos detection was
      associated with low wind speed (P = 0.012) and high temperature (P = 0.015), and
      detection at one site was associated with detection at another (P < 0.001).
      Chlorpyrifos detection was also associated with domestic applications within the
      town area as reported by pesticide applicators (P = 0.045). Peak agricultural use
      of chlorpyrifos did not coincide with peak detection periods. None of the
      detected organochlorines is registered for agricultural use, although at the
      time, heptachlor was permitted for use as a domestic termiticide. Even in a
      semirural town with nearby widespread use of agricultural chemicals, community
      exposures to pesticides in ambient air may largely relate to their
      nonagricultural use.

PMID- 7578536
TI  - Readmissions to hospital: the contribution of morbidity data to the evaluation of
      asthma management.
AB  - We evaluated hospital readmission as an indicator of the quality of management of
      asthma patients, between July 1989 and June 1990. Using hospital separation data,
      we constructed a matched data set to identify early (within two weeks of
      discharge) readmissions. Of over 14,000 admissions for asthma in the 1-to-44-year
      age group, 2.8 per cent were classified as early readmissions. Admissions and
      readmissions were more common in rural than metropolitan areas. Admissions were
      most common during autumn, but early readmissions occurred most often during
      spring. Patients staying more than one day were 0.5 times (95 per cent confidence
      interval (CI) 0.37 to 0.68) as likely to have an early readmission than patients
      staying less than one day. Using the same data set, we identified patients who
      had the potential for readmission within a six-month period. Of the 5052
      patients, 17.8 per cent were readmitted at least once during the period; 3.7 per
      cent had at least one early readmission, and 15.8 per cent had at least one late
      readmission (more than two weeks following discharge). A length of stay of more
      than one day was associated with 0.41 times (CI 0.24 to 0.70) the risk of early
      readmission in this cohort. A length of stay of more than one day was associated
      with a higher risk of late readmission (1.52, CI 1.09 to 2.12), which was less
      likely to occur in rural than metropolitan areas (0.45, CI 0.37 to
      0.55).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578537
TI  - Recall, retention, utilisation and acceptability of written health education
      materials.
AB  - The effects of two distribution strategies on the recall of receipt, retention,
      utilisation and perceived acceptability of written health education materials
      were investigated in two semirural communities. We randomly selected 512 people,
      212 from general practitioners' surgeries, who received the materials from their
      general practitioners at the end of a routine consultation, and 300 from the
      electoral register, who received it through the mail in a personally addressed
      envelope. Of all those who received the materials, 55 (10.7 per cent) were not
      contactable and 386 (84.5 per cent) of those contacted consented to the survey.
      Structured interviews were conducted with consenting individuals two weeks after
      distribution to assess recall of receipt, retention, utilisation and perceived
      acceptability. Of those receiving the material by mail, 77.4 per cent recalled
      receiving it, 75.4 per cent reported keeping the booklet and 66.7 per cent
      reported reading it. Of those receiving it from a general practitioner, 90.9 per
      cent recalled receiving it, 93.3 per cent reported keeping the booklet and 56 per
      cent reported reading it. Perceived acceptability of the material was high, with
      over 80 per cent of respondents finding it very or fairly eye-catching,
      believable, interesting and easy to read. Although general practitioner
      distribution led to higher rates of receipt and retention, mail-out distribution
      led to higher utilisation rates and allowed access to a larger proportion of the
      population, resulting in more people being exposed to the education message.

PMID- 7578538
TI  - Age and secular trends in risk factors for cardiovascular disease in Busselton.
AB  - Mortality rates from heart disease and stroke in Australia have been falling for
      more than 20 years. No completely satisfactory explanations for this trend exist.
      However, it is believed to be due, at least in part, to changes in the incidence
      of cardiovascular disease arising from changes in the prevalence and severity of
      risk factors for cardiovascular disease. The adult community of Busselton in
      Western Australia participated in cross-sectional health surveys every three
      years from 1966 to 1981. This paper describes secular trends from 1966 to 1981
      and age trends from 25 to 80 years for cardiovascular risk factors in Busselton
      men and women. Downwards secular trends were observed for mean blood pressure and
      smoking for men and women, upwards trends were observed for body mass index in
      men, and mean cholesterol was approximately constant over this period. The age
      and secular trends were consistent with other Australian studies conducted in the
      1980s and with overseas studies. An estimated 67 per cent of the decline in
      cardiovascular mortality rates among Busselton men and 22 per cent of the decline
      among Busselton women may be attributed to changes in the prevalence of risk
      factors for cardiovascular disease.

PMID- 7578539
TI  - Sun damage in teenagers' skin.
AB  - A noninvasive method of assessing the degree of sun-induced skin damage was used
      to estimate the prevalence of skin damage in teenagers in four cities in
      Australia and one in Scotland. Information about age, sex and complexion
      characteristics was obtained from 1307 students aged 13 to 15 years. Silicone
      rubber casts were taken of the skin of the students' hands and classified as
      showing either no or mild skin damage. Between 40 and 70 per cent of the
      Australian students had detectable skin damage, compared with about a third of
      Scottish students of the same age. In a multivariate analysis, the risk of having
      sun-damaged skin in the teenage years was up to seven times higher for Australian
      residents than for Scottish residents. Other risk factors were male sex (odds
      ratio (OR) 4.3), blistering on exposure to sun (OR 2.6), and having blond hair
      (OR 2.0), red hair (OR 5.3) or freckles (OR 2.7). The high prevalence of sun
      induced skin damage at such a young age reinforces the need to encourage sun
      protection behaviour in Australian children and teenagers.

PMID- 7578540
TI  - Use of hormone replacement therapy by Melbourne women.
AB  - Hormone replacement therapy (HRT) is used for relief of symptoms related to the
      menopause and for the prevention of postmenopausal osteoporosis and
      cardiovascular disease. Patterns of use of HRT are thought to be changing
      rapidly, but little is known about who is using the therapy, for what purpose or
      for what period of time. Telephone interviews were conducted in May 1991 with a
      randomly selected sample of 2001 Australian-born women aged 45 to 55 years living
      in Melbourne, as part of the Melbourne Women's Midlife Health Project. Questions
      related to use of HRT, health status, use of health services, sexual functioning,
      attitudes to menopause and aging, and sociodemographic characteristics. Twenty
      one per cent of the sample were using HRT. Use was more prevalent among women 50
      years and over (28 per cent) than those under 50 (15 per cent). Seventeen per
      cent of nonhysterectomised women, 31 per cent of hysterectomised women and 49 per
      cent of women who had undergone hysterectomy and bilateral oophorectomy were
      current users. Almost 60 per cent had been using the therapy for two years or
      less, and 34 per cent for one year or less. Just over half reported control of
      hot flushes as a benefit, and 10 per cent mentioned prevention of bone loss as a
      benefit. Logistic regression analysis identified differences between users and
      nonusers in experience of hot flushes, health status, use of preventive and
      treatment services, sexual functioning, wellbeing, attitudes to menopause and
      aging, and sociodemographic characteristics. These differences may relate to risk
      of later cardiovascular disease.

PMID- 7578542
TI  - Community attitudes to bans on smoking in licensed premises.
AB  - Information about public attitudes to the restriction of smoking in licensed
      premises could provide an impetus for a campaign to address the failure of the
      industry to improve the health of its employees and the public. A probability
      sample of 816 people was surveyed to determine community attitudes to the
      introduction of bans on smoking in licensed premises. A total ban on smoking was
      supported by 20 per cent and provision of special smoking areas by 65 per cent,
      and 15 per cent wanted no bans. More-educated people, white-collar workers,
      nonsmokers and those who went to licensed premises less than weekly were more
      likely to support bans than were the less educated, blue-collar workers, smokers,
      and those who went to licensed premises at least weekly. The less educated,
      smokers and those who went to licensed premises at least weekly were most likely
      to perceive that the introduction of smoking bands would reduce their patronage
      of licensed premises. Nonsmokers and those with more than 12 years of education
      were more likely to report that their patronage would increase if bands were
      introduced than were smokers and the less educated. The introduction of bans on
      smoking in licensed premises would result in only a small loss of patronage after
      accounting for potential increases from supporters of bans. The effect of the
      bans is likely to be felt most strongly among the less educated, smokers and
      regular patrons.

PMID- 7578541
TI  - Patterns of common drug use in teenagers.
AB  - To ascertain current levels of drug use among teenagers and to examine
      interrelationships in use, a two-stage cluster sample of Victorian secondary
      school students in years 7 (aged 12 to 13 years), 9 (14 to 15 years) and 11 (16
      to 17 years) were surveyed using a questionnaire on computer. Tobacco use and
      alcohol consumption were evaluated by self-reported frequency of use and seven
      day retrospective diaries. Marijuana and coffee consumption were assessed by self
      reported frequency of recent use. The questionnaire was completed by 2525, a
      participation rate of 83 per cent. Tobacco use rose with year, with 24 per cent
      of young women and 16 per cent of young men in year 11 being regular smokers.
      Trends across year level for heavier alcohol consumption were also observed, with
      just under 10 per cent of year 11 students reporting a weekly consumption higher
      than the current recommended guidelines for adults. Strong interrelationships in
      drug use were found, with a pattern of association between smoking and drinking
      consistent with a mutual elevation of risk. Frequent use of tobacco and alcohol
      had a high risk for associated marijuana use. Coffee consumption carried a
      significant independent association with regular smoking. Teenage substance use
      is common and most occurs at low level and frequency. However, for a substantial
      and increasing minority across the teenage years, high levels of tobacco and
      alcohol consumption potentially compromise health. Frequent alcohol or tobacco
      use rather than heavy intermittent consumption is most likely to be associated
      with concurrent substance use potentially damaging to health.

PMID- 7578543
TI  - Mental health services in Sydney nursing homes.
AB  - Senior nursing staff of the 58 nursing homes in one health area of Sydney were
      interviewed concerning mental health services and staff education. One or more
      psychiatrically trained staff were employed in 45 per cent of the nursing homes.
      Most nursing homes received services from a psychiatrist or another mental health
      professional, but the average time per month provided by them to see residents
      was less than one hour in 18 (31 per cent), one to two hours in 16 (28 per cent),
      and three hours or more in only 11 (19 per cent). Forty-four (76 per cent) wanted
      more mental health services to be provided, especially for advice on management
      of disturbed behaviour. A substantial number of the nursing homes (at least 28
      per cent) provided no ongoing education to their staff about dementia or other
      psychiatric problems. There is good reason to encourage greater use of mental
      health professionals in Sydney nursing homes; enhanced funding of area
      psychiatric services for elderly people is desirable to allow these services to
      be more readily available.

PMID- 7578544
TI  - The syringe in the machine.
AB  - This paper is a report on focus-group discussions with Western Australian and
      South Australian injecting drug users and South Australian drug workers, about
      the feasibility of and issues surrounding the introduction of needle-and-syringe
      vending machines in Australia. Injecting drug users and workers supported the
      idea of introducing vending machines in Australia to complement existing services
      that provide sterile injecting equipment. The participants emphasised that the
      machines should be provided in addition to existing services. Possible adverse
      effects of their introduction included concerns for the safety of minors who are
      not drug users. The potential benefits to public health includes further reducing
      that proportion of the sharing of injecting equipment that is related to
      unavailability of sterile equipment (usually at times when other services do not
      operate).

PMID- 7578545
TI  - Collecting food-related data from low socioeconomic groups: how adequate are our
      current research designs?
AB  - Australian researchers examining the relationship between socioeconomic status
      and food-related behaviour have often selected their samples from the electoral
      roll and then collected their data using a mail-survey method. These studies have
      generally found statistically significant associations between socioeconomic
      status and behaviour, although these relationships are usually only weak-to
      moderate in strength. Given the consistent and strong pattern of association
      between socioeconomic status and mortality, and diet and mortality, there is a
      possibility that these studies may have used a research design that
      underestimates the magnitude of the association. To assess this possibility,
      results obtained using an electoral-roll sample and mail-survey method were
      compared with findings obtained by administering the same questionnaire directly
      to a sample of indigent clients contacted through a welfare agency. The
      comparison suggests that studies that draw their samples from electoral rolls and
      then collect data using a mail-survey questionnaire may greatly understate the
      level of socioeconomic inequality in food-related behaviour in the wider
      community.

PMID- 7578546
TI  - Socioeconomic indices and suicide rate in Queensland.
AB  - Suicides identified from a suicide register were classified according to
      socioeconomic indices of statistical local areas. Suicide rates were correlated
      with socioeconomic disadvantage, as measured by the proportion of persons of low
      income, low education and high unemployment living in an area. Suicide rates were
      inversely related to the proportion of families on high income, who owned their
      homes and who had large houses. Suicide rates of older people (55 years and over)
      were least influenced by these factors. For females, only the most disadvantaged
      areas had higher suicide rates. In other age and sex groupings, relationships
      were mostly linear.

PMID- 7578547
TI  - Hepatitis C and young drug users: are they about to join the epidemic?
AB  - This study investigated what some high-risk youth in Perth knew about, believed
      about and did about hepatitis C, and the extent to which they had been exposed to
      the virus, by surveying 234 12-to-20-year-old users of injectable drugs. About
      half of the respondents (108) gave a blood sample for anonymous hepatitis C virus
      antibody testing. All respondents had used at least one illicit drug other than
      marijuana in the previous 12 months and most (75 per cent) reported injecting
      drugs at least once in the past 12 months. The study group was obtained through
      drug treatment agencies and interviewer networks. Although more than 80 per cent
      of the study group had heard of hepatitis C, only 50 per cent considered the
      infection to be a serious problem. Eighty per cent of respondents were at risk of
      infection from unsafe injecting practices, and their relevant knowledge of
      hepatitis C was at best, barely adequate. Of those tested, 5.5 per cent were
      seropositive. A pool of infection, albeit small, already exists among this group
      of users of illicit drugs. Given the low average duration of illicit drug use
      among this group (less than 2 years) and the fact that many of the users are part
      of a hidden population that will probably never be in treatment, that there is
      any infection present is of concern. Appropriate, well-aimed education and peer
      outreach programs are desperately needed if the transmission of hepatitis C among
      young users of injectable drugs is to be kept to a minimum.

PMID- 7578548
TI  - Public health aspects of tattooing among Australian adults.
AB  - Medical, criminological and psychiatric literatures have pointed to risks
      associated with tattooing, but most of this work has been conducted with samples
      which have other known risk factors or disturbances. This paper investigates the
      reasons, experiences, methods, and perceived consequences of obtaining tattoos
      among a sample of Australian adults. The findings complement, extend and in some
      respects contrast with earlier research. Like other researchers, we found that
      most people acquire tattoos when they are relatively young. Unlike earlier
      research, we did not find widespread dissatisfaction and regret. Sex differences
      emerged in location and design of tattoos. A majority of tattooed people report
      awareness of others' negative stereotypes of them.

PMID- 7578549
TI  - Food consumption of parents on low incomes.
AB  - In the Redfern area in metropolitan Sydney, there are many people on low incomes
      living in public housing. To investigate their nutritional status, a sample of 60
      parents in this area was interviewed; 51 participants completed a food frequency
      questionnaire. Participants also completed weighed food records. The weighed food
      records showed energy intakes lower than expenditure calculated as necessary to
      maintain body weight (as estimated by the Schofield equation and activity
      factor). Therefore, the data are unlikely to be accurate and are not reported
      here. The food-frequency questionnaire indicated energy intakes close to those
      required to maintain body weight. Recorded nutrient intakes were similar to those
      recorded in other Australian studies. Fat supplied 35.6 per cent of the energy in
      the diets of the sample, compared to 37.3 per cent in the National Dietary
      Survey. Although the results were obtained by convenience sampling and may not be
      representative, the results do suggest that some parents on low incomes are able
      to maintain nutrient intake similar to that of the wider community.

PMID- 7578550
TI  - Poststructuralism and other 'species' in public health--a 'Darwinian' view.
AB  - The concepts and methods of poststructuralism are emerging as useful tools to
      increase our understanding of public health. This paper discusses
      poststructuralism within the context of a metaphoric 'evolutionary ecology' of
      knowledge (an epistemecology). It argues that claims for the importance of any
      programs (such as poststructuralism) are problematic. Using evolutionary and
      ecological metaphors, it suggests that public health may benefit from its
      advocates fostering the recombination of elements of knowledge to produce
      epistemes which adapt us congruently to the general and specific goals of public
      health, which should include a primary aim of minimising suffering. Choosing to
      act in an ethical way in regard to our construction and use of knowledge may be
      one way of achieving those aims. The term 'ethical fitness' is a way of
      conceptualising an evolving epistemic ethic.

PMID- 7578551
TI  - How much alcohol in Western Australia is consumed in a 'hazardous' or 'harmful'
      way?

PMID- 7578552
TI  - Canuck Place: the tradition continues. Interview by Rosette Cannata.

PMID- 7578555
TI  - Agency consultation program. A framework for all facilities.

PMID- 7578553
TI  - Child health 2000. Practicing our research. Researching our practice.

PMID- 7578554
TI  - A nurse is a nurse?

PMID- 7578556
TI  - Bike helmet legislation. A lesson in patience and persistence.

PMID- 7578557
TI  - Cope, choose or change.

PMID- 7578558
TI  - Nurse practitioners: expanding the role of nursing.

PMID- 7578559
TI  - [Antigenic structure of the Bordetella pertussis pertactin Pro-rich segment 536
      566. I. Preparation and analysis of antisera to synthetic peptides].
AB  - Rabbit antibodies to four synthetic peptides from the Pro-rich sequence of B.
      pertussis P.69 have been obtained. Prior to immunization, peptides
      KAPPAPKPAPQPGPQPP (17P), QPPQPQPEAPAPQP (14P), GPQPPQPPQP (10P) and PGPQPP (6P)
      were conjugated with keyhole limpet hemocyanin (KLH). Immunoenzymatic analysis
      revealed the following antibody titers: 1:4,000,000 (17P), 1:64,000 (14P) and
      1:256,000 (10P). Serum antibodies to KLH-6P did not react with 6P-coated plates
      but interacted with the hexapeptide in the ovalbumin-6P conjugate. The sera to
      KLH-14P effectively recognized glutaraldehyde-formed epitopes. Using indirect
      immunoassay and competitive assay, it was shown that antisera to KLH-17P, KLH
      14P, KLH-10P and KLH-6P did not react with unrelated antigens. Sera and affinity
      purified antibodies to peptides 10P, 14P and 17P recognized native pertactin with
      variable efficiency.

PMID- 7578560
TI  - [Regulation of the supramolecular structure and catalytic activity of D
      glyceraldehyde-3-phosphate dehydrogenase in systems of reversed Aerosol OT
      micelles in octane].
AB  - Reversible formation of various oligomeric forms of rabbit skeletal muscle D
      glyceraldehyde-3-phosphate dehydrogenase (GAPD) in reversed micelles of Aerosol
      OT in octane at variable degrees of hydration (size) of the micelles, has been
      demonstrated. All the oligomeric forms of the enzyme possess a catalytic activity
      in the reversed micelle system. Data from the sedimentation analysis provide
      evidence for the formation of a monomer, a dimer and a tetramer of GAPD. The
      peculiarities of the structure of oligomeric forms of the enzyme revealed in
      fluorescence studied are discussed.

PMID- 7578561
TI  - [Interaction of 2Fe-2S-ferredoxins from plants and adrenal cortex with
      detergents].
AB  - The interactions of 2Fe-2S ferredoxins from bovine adrenal cortex, blue-green
      algae and leaves of three plant species with some positively and negatively
      charged as well as with uncharged detergents, have been studied. These
      interactions generally resulted in the destruction of active centers of
      ferredoxins represented by the 2Fe-2S cluster. The role of oxidants (oxygen and
      potassium ferricyanide) in cluster destruction by detergents has been
      established. The opposite sensitivity of plant and animal ferredoxins to anionic
      and nonionic detergents was revealed.

PMID- 7578563
TI  - [Thermoinactivation of NAD-kinase from rabbit liver].
AB  - Thermal inactivation of homogeneous NAD-kinase and its partially purified
      preparation containing NAD-kinase in complex with glutamate dehydrogenase has
      been studied. The complex is more resistant to thermal inactivation in comparison
      with isolated NAD-kinase; its inactivation consists in irreversible dissociation
      preceded by a period of constant activity. No period of constant activity is
      observed when homogenous NAD-kinase is subjected to thermal inactivation, which
      represents a two-step process. At the first stage tetramers reversibly dissociate
      into dimer, while at the second stage the dimers are denatured. The values of
      activation energy of dissociation and denaturation are equal to 40 and 52
      kcal/mol, respectively.

PMID- 7578562
TI  - [Equilibrium and kinetic parameters of the interaction of strophanthin K and its
      peroxidase conjugates with soluble and immobilized specific antibodies].
AB  - Using solid phase enzyme-linked immunoassay (ELISA), rate constants for the
      formation and dissociation as well as equilibrium dissociation constants for
      strophanthin complexes interaction with specific antibodies (both soluble and
      immobilized on activated polystyrene beads and polyamide membranes) have been
      determined. A satisfactory correlation was found between dissociation constants
      for immune complexes determined by ELISA (both soluble and immobilized ones) and
      associations constants for these complexes determined by the Scatchard method.
      The experimental values of kinetic and equilibrium constants for strophanthin K
      and its peroxidase complexes interaction reflect the difference in the nature of
      interacting particles and their environment. Strophanthin complexes with
      antibodies appeared to be more stable when formed on adsorbents (in comparison
      with those formed in solution). Strophanthin interaction with immobilized
      antibodies occurred at a slower rate than that with soluble antibodies.
      Strophanthin reacts with antibodies more readily than its complexes both in
      solution and on solid matrices of various polymeric nature.

PMID- 7578564
TI  - [Some properties of multiple forms of transketolase from baker's yeast].
AB  - It has been shown that transketolase A does not differ from the enzyme earlier
      described in the literature by a number of properties (lack of intersubunit
      disulfide bonds, identical number of sulfhydryl groups, two values of Km for
      thiamine pyrophosphate and identity of their absolute values). Transketolase C
      subunits are linked together by disulfide bonds; their total number in the enzyme
      molecule is five (transketolase C-1) or six (transketolase C-2). The Km values of
      transketolase C-1 for thiamine pyrophosphate are commensurate with those of
      transketolase A. Transketolase C-2 has only one Km value for thiamine
      pyrophosphate which is close to one of the two Km values for transketolase A. The
      maximal rate values for transketolases C-1 and C-2 with dihydroxyacetone as
      substrate differ by more than one order of magnitude.

PMID- 7578565
TI  - [Enzymatic synthesis of dihydroxyethylthiamine pyrophosphate, its optical
      characteristics, and quantitative determination].
AB  - Modification of the method of Holzer et al. for the synthesis and purification of
      dihydroxyethylthiamine pyrophosphate, an intermediate of the transketolase
      reaction, is described. Absorption and circular dichroism spectra as well as the
      molar coefficient of circular dichroism absorption at 273 nm are presented. A
      convenient and rapid procedure for quantitative determination of
      dihydroxyethylthiamine pyrophosphate in solution where it is present as the only
      component or as a mixture with thiamine pyrophosphate (or other optically
      inactive compounds), is proposed.

PMID- 7578566
TI  - [The effect of modifying the lysine-83 residue on the thermal stability of myosin
      subfragment 1 and changes in it caused by nucleotide binding].
AB  - The effects of trinitrophenylation of lysyl residues of rabbit skeletal myosin
      subfragment 1 (S1) on thermal denaturation of S1 in the absence of nucleotides,
      in the presence of ADP and within S1 complexes with ADP and Pi analogues,
      orthovanadate (Vi) or beryllium fluoride (BeFx), have been studied by
      differential scanning calorimetry. It has been shown that lysyl
      trinitrophenylation significantly affects the thermal stability of S1, changes
      its domain structure, promotes the decomposition of S1.ADP.Vi and S1.ADP.BeFx
      complexes, and strongly prevents the structural changes in the S1 molecule
      induced by the formation of the S1.ADP.Vi complex without any effect on the
      thermal stability of S1 within S1.ADP and S1.ADP.BeFx complexes. It has been
      demonstrated that the effects of trinitrophenylation on the S1 structure are
      mainly due to specific modification of the epsilon-amino group of the Lys-83
      residue.

PMID- 7578567
TI  - [Study of squirrel myoglobin. Oxidation-reduction reaction between squirrel
      oxymyoglobin and ferricytochrome c].
AB  - Metmyoglobin (met-Mb) of Yakutian ground squirrel (Citellus undulatus) was
      isolated from skeletal muscles and fractionated using gel and ion-exchange
      chromatography. An electrophoretically homogeneous major fraction of met-Mb (pI
      7.05) was obtained with a 90% yield. The rates of the redox reaction between
      ground squirrel oxy-Mb and horse and ground squirrel ferri-Cyt c were studied in
      the pH range of 5-8 at ionic strengths ranging from 0.01 to 1. The experimental
      results were compared to the earlier obtained data for sperm whale and pig Mbs
      whose three-dimensional structures and physico-chemical properties are well
      studied. It was shown that the properties of ground squirrel Mb are very similar
      to those of pig Mb but differ from those of whale Mb. The amino acid sequences of
      about 50 Mbs from various mammals as well as from some avian and chordate species
      (Protein Data Bank) were compared. It was found that rodent myoglobins can be
      divided into two distinct groups. Myoglobins of animals living in water are
      identical with those of sperm whale and other cetaceans, while myoglobins of
      ground rodents closely resemble pig Mb. The number of non-homologous amino acid
      substitutes in each of the two groups (1-2 positions) is much less compared to
      all rodent myoglobins (8 positions). The charge structure of the Mb contact site
      interacting with Cyt c in the course of the electron transfer reaction is
      strictly conservative for all mammalian Mbs tested in this study (but not for
      birds and chordates). It is assumed that under certain extreme conditions oxy-Mb
      can directly interact with cell organelles, such as mitochondria.

PMID- 7578568
TI  - [Effect of protein inhibitors of mitochondrial ATPase in intact rat thymocytes
      and Ehrlich ascites carcinoma cells].
AB  - It has been found that inhibition of mitochondrial ATPase in living thymocytes
      and Ehrlich ascites carcinoma (EAC) cells after incubation of cells with
      uncoupler, rotenone or cumene hydroperoxide, depends, in a large measure, on the
      inhibitor protein (IF1) action. Maximum inhibition (up to 70% of the oligomycin
      sensitive ATPase activity) was found in the presence of the uncoupler in the
      incubation medium. Even when IF1 action was maximum, the residual ATPase activity
      caused marked ATP depletion in thymocytes, while in EAC cells other ATP-consuming
      processes prevailed. No inactive ATPase-IF1 complexes were found in intact
      thymocytes and EAC cells. The extent of inhibition of mitochondrial ATPase under
      oxidative stress was higher in thymocytes than in EAC cells and depended on
      cumene hydroperoxide concentration and duration of cell cellular ATP depletion.
      It is suggested that under certain experimental conditions IF1 can prevent cell
      death by slowing down the hydrolysis of cellular ATP.

PMID- 7578569
TI  - [Anomalous transport of cations upon stimulation of a Ca-dependent K-channel in
      rehydrated erythrocytes].
AB  - The Ca(2+)-dependent potassium transport in human erythrocytes dehydrated into
      hypertonic sucrose solutions and further rehydrated into isotonic media of NaCl
      and KCl, has been studied. Analysis of controversies between potassium release
      and volume changes showed that a new transport mechanism for monovalent cations
      might be activated in rehydrated cells which is silent in normal cells.

PMID- 7578570
TI  - [Permeability of the Escherichia coli outer membrane for ethidium ions and
      periplasmic alkaline phosphatase during increased synthesis of it].
AB  - During augmented synthesis of periplasmic alkaline phosphatase by various strains
      of Escherichia coli, the outer membrane of bacterial cells becomes permeable for
      both the enzyme and ethidium ions which do not generally penetrate inside the
      cells of gram-negative bacteria. In the absence of the lipoprotein in the outer
      membrane, its permeability for these compounds as well as its sensitivity to
      membranotropic agents increases, thus testifying to the influence of the
      lipoprotein upon certain properties of the outer membrane. A competitive
      interaction was found between the lipoprotein and lipopolysaccharide content in
      the outer membrane and their content and alkaline phosphatase secretion into the
      external medium. It is suggested that increased permeability of the E. coli outer
      membrane during augmented synthesis of the secreted protein is due to impaired
      biogenesis of membrane components.

PMID- 7578571
TI  - [Effect of ligands on rotational mobility of Na,K-ATPase].
AB  - Phosphorescence anisotropy of eosin-5'-isothiocyanate labelled Na,K-ATPase
      purified from duck salt glands has been studied. The initial anisotropy value is
      0.235 +/- 0.015 (room temperature) and does not depend on the enzyme conformation
      (sodium or potassium). The experimental curve is fitted into a two-exponential
      curve with residual term, the fast component corresponds to the rotational
      mobility of the functional unit of Na,K-ATPase (promoter), while the slow one--to
      that of larger associates. In the presence of ligands modifying the
      conformational state of Na,K-ATPase (sodium, potassium, ATP) the rotational
      mobility of the fast component does not change in contrast with the slow one. A
      comparison of the enzyme rotational mobility in the presence of ligands
      simulating different steps of hydrolytic cycle suggests that interprotomer
      interactions are changed in the course of hydrolytic cycle: the fraction of
      larger associates increases at the step of the enzyme interactions with potassium
      ions, whereas their mobility in the bilayer enhances sharply after interaction
      with ATP. In the presence of the 2% non-ionic detergent, C12E9, the initial
      anisotropy value decreases down to 0.1; the residual term disappears thereby,
      while the curve is still two-exponential. However, the difference in the
      rotational mobility of sodium and potassium conformers diminishes. At the same
      time, the ratios between protomers and oligomers in the presence of sodium and
      potassium become approximated. This indicates that in the presence of the
      detergent high molecular weight associates are solubilized, the mobility of the
      both protomers and oligomers of Na,K-ATPase increases, while the difference
      between the mobilities of sodium and potassium conformers is disappeared.

PMID- 7578572
TI  - [Import of a modified form of a cytochrome P450scc precursor into mitochondria
      from various sources].
AB  - An Escherichia coli strain providing hypersynthesis of a recombinant cytochrome
      P450scc precursor supplemented with the extra MetArgGlySerHis6GlyIleArg sequence
      at the NH2-terminus (6His-pP450scc) has been constructed. A procedure for
      isolation and purification of 6His-pP450scc from the cell homogenate has been
      elaborated. It has been found that the recombinant precursor is imported into
      isolated rat liver and rat heart mitochondria as well as into yeast mitochondria.
      The import is coupled with proteolytic processing resulting in the mature size
      form of cytochrome P450scc. Modification of the targeting P450scc presequence
      resulting in its increased positive charge is supposed to relieve tissue-specific
      restrictions on the P450scc import into mitochondria.

PMID- 7578573
TI  - [Do glycoproteins IIb/IIIa participate in activation of human platelet s by low
      density lipoproteins?].
AB  - Low density lipoproteins (LDL) enhance the entry of Ca2+ and other bivalent
      cations via receptor-operated channels. The use of a synthetic peptide and
      antibodies blocking the glycoproteins IIb and IIIa interaction with ligands
      revealed that fibrinogen receptor antagonists prevent platelet aggregation
      without any effect on the ability of LDL to increase the cytoplasmic Ca2+ level.
      These data indicate that glycoproteins IIb-IIIa are not involved in the
      activation of the second messenger system by LDL but play a role in the
      proaggregant effect of LDL by providing cell-to-cell interactions.

PMID- 7578574
TI  - [Lack of serum causes apoptosis of thymocytes not requiring protein synthesis and
      ATP generation].
AB  - Incubation of rat thymocytes in serum-free media was found to result in their
      apoptotic death characterized by internucleosomal DNA fragmentation, nuclear
      pyknosis and subsequent irreversible plasma membrane damage. As in the case of
      glucocorticoid (hydrocortisone)-induced apoptosis, DNA fragmentation under serum
      withdrawal was suppressed by endonuclease inhibitors (Zn2+ and spermine). At the
      same time, protein synthesis inhibitors (cycloheximide and puromycin) failed to
      block the apoptosis induced by serum withdrawal but inhibited the hydrocortisone
      induced apoptosis. Various inhibitors of oxidative phosphorylation (uncoupler,
      rotenone, oligomycin), causing sharp decrease in cellular ATP did not suppress
      DNA fragmentation, whereas thymocyte plasma membrane damage accelerated under
      their effect. The results obtained indicate that intact thymocytes contain all
      the components of the apoptotic system; however, in the absence of apoptotic
      stimuli (e.g., hydrocortisone) the system is blocked by some growth factors of
      serum origin. Serum withdrawal is sufficient by itself to induce apoptosis and
      does not require the synthesis of special proteins.

PMID- 7578575
TI  - [Endogenous cellular reverse transcriptase in the rat brain. A comparative
      analysis of the authentic enzyme and recombinant reverse transcriptase coded by a
      mobile genetic element of the LINE class].
AB  - A purified preparation of endogenous RNA-dependent DNA-polymerase (reverse
      transcriptase) earlier identified in rat brain (Ivanov, V.A., Pakhotin, P.I.,
      Bobkova, N.V., and Ilyin, Yu.V. parallel Dokl. RAN (1992). V. 323, P. 173-177)
      has been obtained. A comparative analysis of the enzyme and recombinant reverse
      transcriptase coded by the mobile genome element jockey earlier expressed in a
      heterological cell system (Ivanov V.V., Melnikov A.A., Siunov A.V., Fodor I.I.,
      Ilyin, Yu.V. parallel EMBO J. (1991), V. 10, P. 2489-2495) has been carried out.
      Like retroviral RNA-dependent DNA-polymerases, these enzymes show preference for
      polyribonucleotides and can use poly(rCm) as template. Besides they are inhibited
      by SH-reagents and require bivalent cations (Mg2+ or Mn2+) and detergent and/or
      KCl as ionic strength carrier. The enzymes differ drastically from retrovirus
      reverse transcriptases by a number of catalytic properties (low optima of
      concentration of requisite cations and ionic strength, strong preference for
      Mn2+, highly efficiency in using poly(rCm), lack of associated RNase H activity)
      but exhibit a high degree of similarity among themselves with regard to the above
      properties. It is suggested that endogenous reverse transcriptase from rat brain
      is a product of expression of the mobile genome element of the LINE family.

PMID- 7578576
TI  - [Thermodynamic parameters of complex formation of blood plasma fibronectin and
      myeloperoxidase].
AB  - Previous studies have demonstrated that fibronectin immobilized on BrCN-activated
      agarose forms a complex with soluble myeloperoxidase. The affinity of such
      interaction increases after preliminary absorption of fibronectin on a column
      with immobilized gelatin, one of its natural ligands. The thermodynamic
      characteristics of the myeloperoxidase interaction with fibronectin-gelatin
      agarose have been established. The role of fibronectin-myeloperoxidase
      interaction in the inflammation focus is discussed in terms of the mode of the
      phagocyte loading with the enzyme and as a way of protecting intrinsic body
      tissues from injury by oxidants generated by extracellular myeloperoxidase.

PMID- 7578577
TI  - [GeneBee-NET: An Internet based server for biopolymer structure analysis].
AB  - A network server providing biopolymer structure databank retrieval as well as
      some other biocomputing procedures for Internet users is described. Its basic
      procedures consist in looking for sequence and 3D homologies (similarities).
      Found homologies are used for constructing multiple alignment, for predicting RNA
      and protein secondary structures as well as for constructing phylogenetic trees.
      Alongside traditional methods of sequence homology retrieval, a "matrix-free"
      (correlation) method is proposed. A similar procedure is used to locate protein
      3D similarities. For novel procedures algorithm ideas and their possible
      applications are discussed. The service ideology is based on the interaction of
      server and client programs. The client program (GeneBee for IBM PC) can be used
      to form queries to the server as well as to manipulate a treatment result. In the
      absence of the client program the interaction with the server can be in the text
      mode. The E-mail and WWW addresses for the server are as follows:
      SERVE/INDY.GENEBEE.MSU.SU and WWW.GENEBEE.MSU.SU.

PMID- 7578579
TI  - [Halophilic archaea flagella: biochemical and genetic analysis].
AB  - The protein compositions of archaebacteria (Halobacterium salinarium,
      Halobacterium volcanii, Halobacterium saccharovorum and Natronobacterium
      pharaonis 12) flagella have been studied. It was found that flagella of these
      archaebacterial species are made up of flagellins. The flagellins of H.
      salinarium, H. volcanii and H. saccharovorum are glycosylated. Based on the known
      primary sequences of Halobacterium halobium R1M1 flagellin genes,
      oligonucleotides to the 5'- and 3'-ends of locus A containing two out of five
      such genes have been synthesized. The amplified by primers fragment of
      chromosomal DNA coding for H. halobium flagellins A1 and A2 was used as a probe
      for detecting homologous sites in archaebacterial DNA. Southern blotting
      hybridization revealed that the DNA of all archaebacterial species tested in this
      study contains sequences that are homologous to genes flg A1 and flg A2 of H.
      halobium.

PMID- 7578580
TI  - [Correlation of cytotoxic activity of mutant forms of tumor necrosis factor alpha
      with changes in the level of free sphingosine in murine liver].
AB  - Sphingosine, the product of enzymatic degradation of sphingomyelin, displays a
      high cytotoxic activity and is accumulated in animal organs under the action of
      the tumour necrosis factor (TNF alpha). To elucidate the role of sphingosine in
      the realization of TNF cytotoxicity, TNF mutants were obtained which differed in
      their cytotoxic action on L929 cells. The wild strain of TNF and the mutant
      having a deletion in position 67-71 displayed the highest toxicity and sharply
      stimulated sphingosine accumulation in mouse hepatocytes. A moderate increase in
      the sphingosine content was induced by mutants with point and double mutations in
      positions E127Q, I155L and V150I displaying a much lower toxicity in comparison
      with the wild strain. The toxic, mutagenic and antimutagenic activities of
      sphingosine were investigated. Despite the high degree of cytotoxicity,
      sphingosine did not display any mutagenic activity but had a pronounced
      antimutagenic effect on E. coli cells. The role of phospholipid enzymatic
      degradation products in activation of sphingomyelin cycle enzymes stimulating of
      sphingosine accumulation in animal cells under the action of TNF alpha is
      discussed.

PMID- 7578578
TI  - [Modification of the ortho-route in Pseudomonas putida strain 87: purification
      and properties of dienlactone hydrolase].
AB  - Dienelactone hydrolase (DLH) was purified to electrophoretic homogeneity from the
      biomass of the Pseudomonas putida strain 87 grown on 3-chlorobenzoate. The
      specific activity of the purified enzyme is 50.5 U./mg of protein. The enzyme is
      a monomer with a molecular mass of 22 kDa, has a pH optimum at 7.6 and is active
      within a broad temperature range (20-45 degrees C). The enzyme activity is
      inhibited by pCMB (which requires up to two equivalents of the reagent) but not
      by EDTA. The Vmax values of DLH for trans-dienelactone and 2-chlorodienelactone
      are practically identical (247.9 and 247 u./mg, respectively) and exceeded two
      fold that for cis-dienelactone. However, the Km for 2-chlorodienelactone is two
      times as high as that for trans-dienelactone (6.9 and 14.2 microM, respectively).
      A comparison of physico-chemical and kinetic properties of P. putida 87 DLH with
      those of the enzymes responsible for the decomposition of chlorinated and
      fluorinated compounds revealed that the enzyme can be assigned to the third
      group, i.e., the DLH-modified ortho-cleavage path way characteristic of gram
      negative bacteria.

PMID- 7578581
TI  - [Interaction of a monoclonal antibody to P-selectin with activated platelets and
      endothelial cells. Heterogeneity of expressing P-selectin in human aorta
      endothelial cells].
AB  - Monoclonal antibody (MAb) CRC81 against P-selectin, a membrane cell adhesion
      protein of platelets and endothelial cells (EC), has been obtained and
      characterized. The antibody selectively interacted with the surface of activated
      platelets and EC due to the redistribution of P-selectin from intracellular
      organelles onto the surface by activation. MAb CRC81 could recognize not only
      human but also rabbit and dog P-selectins. MAb CRC81 was used to establish the
      heterogeneity of human aorta EC with regard to the P-selectin content. Some of
      the cells in culture did not contain this protein but were nevertheless
      positively stained for von Willebrand factor, a specific marker for EC which,
      similar to P-selectin, is localized in Weibel-Palade's bodies. The proportion of
      P-selectin negative EC increased dramatically in the course of cell passaging: in
      primary cultures of aortic EC their content was about 15%, while after the 6th
      passage it exceeded 90%.

PMID- 7578582
TI  - [Human ovarian ceramides and gangliosides in aging].
AB  - The age dependence of the ceramide and ganglioside content in human ovaries has
      been studied. It has been found that the ganglioside content does not change upon
      ageing, while the ceramide content alters with age, showing initial increase
      around the age of 45-47 years but then drops drastically. The composition of
      gangliosides undergoes drastic changes in the course of time, GM3 and GD3 being
      the major gangliosides in human ovaries. The amount of GD3 increases with age
      with a subsequent reduction of the Cer/GD3 molar ratio. It is suggested that the
      reduction of the Cer/GD3 molar ratio is a "risk factor" in tumour development
      upon ageing.

PMID- 7578584
TI  - [Kinetics of action of phosphorylase kinase in a cascade enzymatic system. III.
      Hysteretic properties of phosphorylase kinase from skeletal muscles].
AB  - The kinetic behaviour of rabbit skeletal muscle phosphorylase kinase at variable
      concentrations of the enzyme and the substrate (glycogen phosphorylase b) has
      been studied. The kinetic curves reveal a lag period whose duration decreases
      with a rise in the phosphorylase kinase concentration (when the reaction is
      initiated by an addition of the ATP + MgCl2 mixture to the enzyme preincubated
      with phosphorylase b, CaCl2, glycogen and glucose-1-phosphate or inorganic
      phosphate). A decrease of the phosphorylase b concentration eliminates the lag
      period. Under these conditions the specific activity of phosphorylase kinase
      decreases with a rise in the enzyme concentration. The kinetic behaviour of
      phosphorylase kinase is interpreted in terms of a model of a linearly associating
      system, such as M reversible M2 reversible M3 reversible ...Mi, where M is the
      dexadecameric molecule of phosphorylase kinase. Acceleration of the phosphorylase
      kinase-catalyzed reaction in the course of the enzymatic process seems to be due
      to the breakdown of inactive enzyme associates (Mi) caused by phosphorylase b.
      The short gamma-subunit of phosphorylase kinase devoid of the calmodulin-binding
      domain does not display any hysteretic properties.

PMID- 7578585
TI  - [Redistribution of Ca2+ ions in Ehrlich ascites carcinoma cells under the action
      of deoxyglucose and inhibitors of the intracellular Ca2+- transporting system].
AB  - Changes in free cytoplasmic Ca2+ ([Ca2+]i) in Ehrlich ascites tumour cells were
      studied under the effect of deoxyglucose and agents which modify transmembrane
      Ca2+ fluxes. It was shown that the reason for deoxyglucose-induced [Ca2+]i
      increase in Ca2+ release from internal stores and the influx from the external
      medium. Mitochondrial metabolic inhibitors (oligomycin+KCN,
      oligomycin++uncouplers of oxidative phosphorylation) induce themselves some rise
      in [Ca2+]i and increase the deoxyglucose effect on [Ca2+]i significantly. The
      conclusion was made that mitochondria can participate in cytosolic Ca2+
      regulation and Ca2+ redistribution in tumour cells.

PMID- 7578583
TI  - [Site-specific endonuclease BspKT8 from the thermophilic strain KT8 of Bacillus
      species].
AB  - A site-specific endonuclease capable of recognizing the sequence 5'-AAGCTT-3' was
      detected and purified to homogeneity from the thermophilic strain of Bacillus
      species KT8. The endonuclease has a molecular mass of 34 kDa and is found in
      solution in a monomeric form. The activity of BspKT8 does not depend on ATP and
      is not stimulated by S-adenosyl-L-methionine. The enzyme displays the highest
      activity with a broad range of temperatures (37 degrees-48 degrees C). Since DNA
      cleavage occurs in accordance with the scheme: [formula: see text] the enzyme can
      be assigned to the class-II of restriction endonucleases and represents an
      isoschizomer of HindIII.

PMID- 7578586
TI  - [Quantitative determination of cattle angiogenin].
AB  - Polyclonal antibodies to a milk antigen were obtained by a standard immunization
      procedure. The possibility was demonstrated to use the peroxidase-antibody
      conjugate in a competitive immunoenzymatic test. The minimal amount of the
      antigen determined by this method is 10 ng/ml.

PMID- 7578588
TI  - Staining etched epoxy resin sections for light microscopy.
AB  - Staining of etched sections for light microscopy is described. Azan staining was
      successful after treatment with potassium dichromate and the use of concentrated
      dye solutions. To remove osmium for hematoxylin-eosin staining, removal by
      reduction with ferrocene was used instead of oxidation. Highly selective
      differentiation after hematoxylin staining was achieved using p-toluenesulfonic
      acid-DMSO. To enhance eosin staining, a 2-bromoethylamine link between eosin and
      the tissue was used. Ferrocene also facilitated counterstaining of nuclei with
      hematoxylin after the PAS reaction. Periodic acid-methenamine silver staining was
      carried out without modification.

PMID- 7578587
TI  - [Participation of the ADP/ATP-antiporter in the uncoupling action of fatty acids
      in liver mitochondria].
AB  - The controversial data on the involvement of the ATP/ADP-antiporter in the
      uncoupling effect of fatty acids in liver mitochondria as well as on the
      sensitivity of the uncoupling process to the ATP/ADP-antiporter inhibitor,
      carboxyatractylate, have been analyzed. It has been shown that in liver
      mitochondria uncoupled by palmitic acid, pyridoxal-5-phosphate, diethyl
      pyrocarbonate and glutamate produce an additional recoupling action against the
      background of carboxyatractylate. No such effect is observed during mitochondrial
      uncoupling by FCCP. Micromolar concentrations of ADP added prior to palmitic acid
      produce a far more potent coupling action; the subsequent recoupling effect of
      carboxyatractylate diminishes thereby. This finding suggests that the reduction
      of endogenous ADP is responsible for the increased sensitivity of the uncoupling
      action of fatty acids to carboxyatractylate. It is concluded that the ATP/ADP
      antiporter and other membrane carriers play a role in the uncoupling action of
      fatty acids on liver mitochondria.

PMID- 7578589
TI  - Vital fluorochromes as tracers for fungal growth studies.
AB  - Eight fluorescent dyes were tested for staining the spores or mycelia of six
      fungi and for their translocation into new growth when the preloaded spores or
      mycelia were incubated on agar coated coverslips. The dyes studied were
      Cellufluor, Nile red, fluorescein diacetate (FDA), carboxyfluorescein diacetate
      (CFDA), chloromethylfluorescein diacetate (CMFDA), aminochloromethyl coumarin
      (CMAC), and the carbocyamines DiIC18(3) and DiOC18(3). The fungi on which the
      dyes were tested included Botrytis cinerea, Fusarium oxysporum f.sp. lycopersici,
      Idriella bolleyi, Pythium oligandrum, Sclerotium cepivorum and Trichoderma
      harzianum. Most of the fluorochromes gave good initial staining of mycelia or
      spores; however, FDA fluorescence faded rapidly during excitation, making it
      impractical for use. Also, the spores and mycelia of B. cinerea and T. harzianum
      sometimes gave weak fluorescence with Nile red, and the spores and mycelia of I.
      bolleyi gave unusually weak fluorescence with Cellufluor. There were other
      variations of staining among the different dye/fungus combinations, but each
      fungus showed strong fluorescence at least one dye. Cellufluor, CMFDA, CMAC and,
      to a lesser extent, CFDA and Nile red, were efficiently translocated into new
      growth from preloaded spores or mycelia, whereas FDA, DiIC18(3) and DiOC18(3)
      were not. The extent of translocation ranged from 0.1 to 1.2 mm in germ tubes
      arising from spores, and from 0.9 to 9.2 mm in mycelia extending from dye-loaded
      agar blocks. The findings suggest that fluorescent dyes could be used as markers
      or tracers in studies of fungal growth and differentiation.

PMID- 7578590
TI  - Histological observations of dental tissues using the confocal laser scanning
      microscope.
AB  - To investigate the time course of mineralization in undecalcified dental tissues,
      calcein- and tetracycline-labeled rat maxillary molar sections were stained with
      Villanueva bone stain en bloc, embedded in methyl-methacrylate (MMA), ground to
      50 microns thickness, and observed by confocal laser scanning microscopy (CLSM).
      This method allowed observation of dental structures including odontoblasts, pulp
      cells and periodontal ligament, and dentinal tubules and enamel rods at high
      resolution; labeled enamel, dentine, and cementum could be observed
      simultaneously regardless of section thickness. CLSM permitted simultaneous
      observation of both the components of calcified tissue and the cellular
      components of dental tissues, and assessment of the mineralization time course of
      hard tissues labeled by tetracycline or calcein. The technique is useful for both
      assessing the elements composing dental structure and observing the histological
      dynamics by which dental structure develops.

PMID- 7578591
TI  - A thionin stain for visualizing bone cells, mineralizing fronts and cement lines
      in undecalcified bone sections.
AB  - A staining method is described using thionin, for undecalcified deacrylated bone
      sections. RNA is stained purplish violet, allowing still active osteoblasts to be
      distinguished from lining cells. Staining intensity of mineralized bone is
      related to the degree of mineralization. Mineralizing fronts and cement lines are
      visualized clearly. Lamellae show an alternate pattern. Histomorphometric
      parameters such as osteon thickness and interstitial bone thickness can be
      measured without using polarized light. The mineralizing front can be assessed
      and expressed as a percentage of the osteoblast-covered interface between osteoid
      and mineralized bone. The stain is also useful for qualitative assessment of
      metabolic bone disease. Thionin stained sections can be kept for at least one
      year when stored in the dark at 7 C.

PMID- 7578592
TI  - A simple and rapid staining technique for plastic embedded cartilage and bone.
AB  - In this report we describe a simple and rapid staining technique for cartilage
      and bone embedded in Araldite. Semithin sections of embryonic vertebrae obtained
      from 15 to 17 day mouse fetuses were stained using an aqueous solution 0.25% with
      respect to methylene blue, 0.25% with respect to azure A, and 0.5% with respect
      to Na2 CO3, then counterstained with 1% aqueous pararosaniline chloride (MAP).
      Results were compared with toluidine blue stained sections. MAP permitted good
      discrimination of developmental stages of both cells and extracellular matrix
      within vertebral ossification centers during endochondral ossification. The
      technique is simple, rapid and applicable to plastic embedded sections, and can
      be used prior to ultrastructural examination.

PMID- 7578593
TI  - Ultrastructural distribution of calcium in cutaneous electroreceptor organs of
      teleost fish.
AB  - The calcium distribution in the ampullary electroreceptor and the type B
      electroreceptor organ (gymnarchomast) of Gymnarchus niloticus (Glymnarchidae) and
      in the tuberous organ of Apteronotus leptorhynchus (gymnotidae) was studied.
      Endogenous calcium appeared as electron-dense precipitates when the cutaneous
      organs were pre-fixed with phosphate-buffered glutaraldehyde and postfixed with
      osmium tetroxide plus potassium bichromate. Calcium precipitates were localized
      in both intracellular compartments of sensory cells, and afferent nerve fibers.
      In contrast to sensory cells, small amounts of calcium precipitates were found in
      the cytoplasm of accessory cells. In sensory cells, electron-dense deposits were
      apparent mainly in synaptic vesicles near synaptic ribbons, inside vacuoles of
      the endoplasmic reticulum, and between the layers of the nuclear membrane. Very
      few deposits were found in mitochondria. Precipitates were also observed within
      the axons of afferent nerves and between the layers of the myelin sheath. The
      synaptic cleft was devoid of calcium. Calcium deposits have a specific cellular
      distribution in electroreceptor organs of teleost fish.

PMID- 7578594
TI  - K-ras gene mutation related to histological atypias in human colorectal adenomas.
AB  - To investigate the relationship of oncogene analysis to morphology, we analyzed K
      ras gene mutations by dot-blot hybridization with and without consideration of
      histological atypias in individual colorectal adenomas. Each of 54 colon polyps
      were divided into two parts after fixation. One part was used as a mass to assess
      point mutations; the remaining portion of each polyp was paraffin-embedded,
      stained with hematoxylin and eosin, and examined for point mutations related to
      histological atypias. In the first part of our study, K-ras gene mutations at
      codon 12 were detected in 13 cases (24%). In the second part of our study, 12
      cases had distinctly different histological atypias. From each of these 12 cases,
      two areas, one with higher or one with lower grade atypia in the same polyp were
      excised to analyze for K-ras gene mutation. Two of these 12 cases (17%) had the
      mutation in different areas of the same tumor. These two cases contained the
      mutation only in the areas with higher grade atypia, and only one case added
      information regarding ras mutation upon microdissection when compared to the
      entire biopsy. These results suggest that oligonucleotide hybridization can
      identify the majority of cases containing ras mutations despite regional
      morphologic variation. Individual cases, however, may contain clonal
      subpopulations within adenomas with different ras sequences from other regions
      within the same adenoma.

PMID- 7578595
TI  - Use of DAPI for anastomosis group typing of strains of the fungus Rhizoctonia
      solani.
AB  - Strains of Rhizoctonia solani, a common soil-borne, pathogenic fungus of plants,
      are assigned to one of 11 anastomosis groups (AGs) based on the occurrence of
      imperfect fusions (anastomoses) between hyphae of a non-typed strain and a tester
      strain of one of the 11 AG's. Imperfect fusion is characterized by the death of
      one or more cells in each of the hyphae involved in the fusion. Although hyphae
      from branches of the same strain of R. solani may fuse with each other (self
      fusion), cell death does not occur. Cell death is accompanied by nuclear
      degradation and granulation, or plasmolysis of the cytoplasm, which often is not
      visible using brightfield microscopy. When the DNA-binding fluorochrome DAPI
      (4',6-diamidino-2-phenylindole) is used and the hyphal fusions viewed under
      fluorescence microscopy, no nuclei are observed in fused hyphal cells from two
      strains of the same AG of R. solani. Because DAPI reacts only with living nuclei,
      lack of staining is presumptive evidence that the fused cells are dead as a
      result of imperfect fusion. The use of DAPI reduces the time required for making
      AG determinations compared to standard methods because it eliminates the need to
      assess cell wall dissolution and cytoplasmic fusion. Also, it is not necessary to
      trace the hyphae involved in the fusion to their respective origins to ensure
      that self-fusion has not occurred.

PMID- 7578596
TI  - Basic blue 148: a rapid stain for T helper cells.
AB  - After brief exposure to an aqueous solution of the oxazine textile dye C.I. basic
      blue 148 following fixation in 37% formalin, 95% ethanol and glacial acetic acid,
      T helper cell nuclei and cytoplasm in specimens of peripheral blood displayed a
      deep red-violet color. No other cell in normal blood or bone marrow specimens
      showed intense staining of this type. The total staining time is 1 min. Basic
      blue 148 stain is a promising technique for hematology and immunology
      laboratories as a rapid screening test for T helper cells in blood specimens
      using a microscopic slide and ordinary incandescent illumination.

PMID- 7578597
TI  - Argyrophilic nucleolar organizer regions and bromodeoxyuridine and 3[H]-thymidine
      labelling indices in colorectal cancer.
AB  - The count of argyrophilic nucleolar organizer regions (AgNORs) has been proposed
      as a useful method for evaluating cell replication in human tumours. The current
      study was undertaken to compare AgNOR values in colorectal cancers with two
      better established methods for investigating cell proliferation such as
      bromodeoxyuridine (BrdUrd) and 3[H]-thymidine (3[H]dT) labelling indices (LIs).
      Because some concern still exists regarding accuracy and reproducibility of AgNOR
      quantifying methods, we carried out a control study by independently repeating
      the same measurements (number, area and area per silver-stained NOR particle) in
      two centres with different operators and computer-assisted image analysers on 40
      colorectal carcinomas. AgNOR values recorded in the two centres were strictly
      correlated (r = 0.75; P < 0.001 for number; r = 0.62, P < 0.01 for area; r =
      0.63, P < 0.001 for area per silver-stained NOR particle) and the range of values
      were almost identical. Then, AgNOR values were compared with BrdUrd and 3[H]dT
      LIs, respectively obtained by in vivo incorporation and in vitro incubation in
      the same series of colorectal carcinomas. No correlation was found between AgNOR
      values and BrdUrd or 3[H]dT LIs. BrdUrd and 3[H]dT LIs were instead reciprocally
      significantly correlated. No evident correlation was seen between LIs or AgNOR
      values and clinico-pathological parameters of the tumour. In conclusion, in
      colorectal neoplasms, AgNOR values did not appear to relate with more direct
      parameters of cell proliferation. It follows that AgNOR reliability as a
      biomarker of cell proliferation remains questionable.

PMID- 7578599
TI  - In vivo labelling with halogenated pyrimidines of squamous cell carcinomas and
      adjacent non-involved mucosa of head and neck region.
AB  - The frequency and distribution of labelled cells were studied
      immunohistochemically in 37 squamous cell carcinomas (SCC) of head and neck after
      in vivo infusion of IdUrd and BrdUrd. Tumours were classified according to their
      labelling patterns. Low and moderate grade SCC consisted of tumour islands
      separated by interstitial tissue. In some tumours labelled cells only appeared
      near the basal layer while in others proliferative cells were evenly distributed
      within the neoplastic island. In anaplastic carcinomas labelled cells were
      distributed either randomly or around blood vessels (cord structures). While the
      basal layer in adjacent normal epithelium contained very few labelled cells (LI =
      1.6 +/- 0.2%), the LI of basal cells in tumour islands were much higher than the
      average LI of the tumour (47.2 +/- 2.8% and 23.8 +/- 1.6%, respectively). In
      patients who had received cytotoxic therapy up to two months before the biopsy,
      the LI in the basal layer of normal epithelium was 19.0 +/- 3.5%. In sequential
      biopsies obtained 1-2 weeks after the infusion of IdUrd and BrdUrd some labelled
      tumour cells were found in necrotic foci and in pearl structures. Additionally,
      in six tumours, we found areas of cells labelled with IdUrd alone, even though
      the IdUrd infusion had been followed by a BrdUrd infusion 1 h later. This is in
      agreement with the phenomenon of intermittent tumour blood flow described earlier
      in experimental tumours.

PMID- 7578600
TI  - Regulation of NIH-3T3 cell G1 phase transit by serum during exponential growth.
AB  - The proliferation rate of mammalian cells is regulated normally in the G1 phase
      of the cell cycle. During this phase, it is convenient to assign positive and
      negative roles to the molecular programs that regulate the duration of G1 and the
      phase transition from G1 to S phase. Density-dependent inhibition of cellular
      proliferation results in an increase in the duration of G1. This form of
      regulation is due to both secreted factors and cell-cell contact. Serum is
      mitogenic to a variety of mammalian cell types. Because quiescent cells enter S
      phase as a result of serum addition to culture media, serum is usually regarded
      as a source of positive regulatory growth factors. We have measured the length of
      the G1, S and G2+M phases of NIH 3T3 cells during exponential growth as a
      function of cell density and serum concentration. The G1 length increases during
      exponential growth as a function of density while S and G2+M are relatively
      constant. Further, this increase in G1 phase time, or density mediated negative
      regulation, is inhibited by increasing serum concentration. This phenotype is
      saturable between 10% to 20% serum. Serum concentrations above 2.5% are able to
      increase the rate of cell cycling (decrease the G1 phase time) by inhibiting
      density dependent negative regulation of NIH 3T3.

PMID- 7578598
TI  - Impaired chromosome segregation in plant anaphase after moderate hypomethylation
      of DNA.
AB  - 10(-6) M and 10(-5) M 5-azacytidine, demethylated around 9% and 17% of the 5
      methylcytosine residues found in Allium cepa L. native DNA, respectively. Both
      treatments stimulated RNA synthesis in the cells of root meristems. On the other
      hand, the 10(-5) M treatment gave rise to multiple chromosomal anomalies in
      mitosis before any fall in the mitotic index was detectable, but no chromosomal
      breaks were ever seen. Serious lesions involved in chromatids and segregation in
      anaphase were preferentially found after hypomethylation of DNA sequences
      replicated in the second half of the previous S period: (i) sister telomeres
      remained unresolved at the cell equator while kinetochores had reached the poles,
      (ii) whole unsegregated chromosomes were pulled to one of the poles by obviously
      disfunctional kinetochores, resulting in an unbalanced distribution of
      chromatids, (iii) unsegregated chromosomes in other cells remained at the spindle
      equator as if kinetochores were nonfunctional, while cytoplasmic division took
      place before their migration to the poles. Frequently, a growing cytokinetic
      plate randomly cut the unsegregated chromosomes, giving rise to aneuploid nuclei.
      These anaphase failures are a firm basis to explain why the 10(-5) M treatment
      selectively depressed the rate of cell proliferation in these cells in the long
      run. On the other hand, if hypomethylation occurred at the first half of the
      previous S period, enlarged chromosomal segments were evident in most metaphases,
      while chromosome laggards and bridges were recorded in anaphase at rather similar
      frequencies after the different 5-azacytidine treatments. These data were
      consistently obtained both in the native mononucleate cells of meristems and in
      one subpopulation of synchronous cells labelled as binucleate by 5 mM caffeine.

PMID- 7578601
TI  - Effect of ethanol on the protein secondary structure of the human gastric mucosa,
      in vitro.
AB  - The effect of ethanol on the secondary conformational structure of proteins of
      the human gastric mucosa was investigated by attenuated total reflection/Fourier
      transform infrared (ATR/FT-IR) spectroscopy. The IR peak intensity and position
      of each structural component of gastric mucosa was found to change significantly
      with the ethanol concentration and length of exposure. The peak intensity due to
      the beta-sheet and/or beta-turn conformational structure in amide I and II bands
      of gastric mucosa clearly increased after treatment with ethanol. Moreover, the
      peak at 1635 cm-1 shifted to 1630 cm-1 after treatment with 40% ethanol for 3 h,
      or 80% ethanol for 1 h, and a distinct shoulder also appeared at 1643 cm-1. This
      shift occurred more rapidly and was more pronounced after exposure of mucosa to
      80% ethanol, compared with the effect of 40% ethanol, but the alpha-helical
      structure at the amide I and II bands was not influenced by either concentration
      of ethanol. Ethanol treatment might also transform the secondary structure of
      amide III in gastric mucosa from an alpha-helix to a mainly random coil with
      extensive unfolding. The absorption between 1180 and 980 cm-1, which is assigned
      to glycoprotein structure, was also reduced after treatment with ethanol. This
      strongly indicates that ethanol influences the conformation of the lipids and
      proteins of human gastric mucosa, leading to their deformation.

PMID- 7578602
TI  - The reticulocyte count and its subfractions in smoking and non-smoking pregnant
      women.
AB  - Our objective was to compare the reticulocyte count and its subfractions in
      smoking and non-smoking women at different stages of normal pregnancy. STUDY
      DESIGN: In 247 non-smoking and 123 smoking healthy pregnant women the
      reticulocyte count and its subfractions were compared at four different stages of
      pregnancy: 0-10, 11-20, 21-30 and 31-40 weeks. Exclusion criteria were a
      diastolic blood pressure > or = 90 mmHg, an endocrine disease or a coagulation
      disorder. Women in the smokers group smoked more than 4 cigarettes a day. Non
      smokers were defined as women reporting no smoking at all. Blood samples were run
      on the Sysmex R-3000 reticulocyte counter. RESULTS: The absolute reticulocyte
      count was lower in the smoking group throughout pregnancy, but this was only
      significant in the last ten weeks of gestation (71.9 x 10(9)/l versus 78.8 x
      10(9)/l). There was no difference between the low fluorescence, the medium
      fluorescence and the high fluorescence proportions in the non-smoking and the
      smoking group. Both groups behaved similarly during pregnancy; there was a
      decrease of mature reticulocytes and a significant increase of more immature
      reticulocytes. CONCLUSION: These data show a moderate measurable effect of
      cigarette smoking on the reticulocyte count and the absence of an effect on the
      reticulocyte subsets.

PMID- 7578603
TI  - Platelet count and platelet indices at various stages of normal pregnancy in
      smoking and non-smoking women.
AB  - Our objective was to compare the platelet count and platelet indices of smoking
      and non-smoking women at different stages of normal pregnancy. STUDY DESIGN: In
      247 non-smoking and 123 smoking healthy pregnant women the platelet count, the
      mean platelet volume, the platelet distribution width and the plateletcrit were
      compared at 0-10, 11-20, 21-30 and 31-40 weeks of pregnancy. Exclusion criteria
      were a diastolic pressure > or = 90 mmHg, an endocrine disease, a coagulation
      disorder, acetylsalicylic acid or phenprocoumon use. A women was considered a
      smoker if she smoked more than 4 cigarettes a day. Non-smokers were defined as
      women reporting no smoking at all. Blood samples were run on the Sysmex NE-8000.
      RESULTS: There was no significant difference between the platelet count in the
      two groups. In the non-smoking group, the platelet count showed a significant
      decrease with gestational age (287 x 10(9)/l to 258 x 10(9)/l). This was not the
      case in the smokers group. The mean platelet volume of the smokers was
      significantly lower than that of the non-smokers in the last ten weeks of
      pregnancy (10.4 fl versus 10.7 fl). The platelet distribution width and the
      plateletcrit did not change under the influence of cigarette smoking. CONCLUSION:
      Smoking during pregnancy does not significantly affect platelet count or platelet
      indices.

PMID- 7578604
TI  - Serum phospholipases A2 after aortobifemoral reconstruction.
AB  - Phospholipase A2 has been implicated in the pathogenesis of local and distant
      tissue injury after ischaemia and reperfusion. A common operation inducing
      ischaemia and reperfusion is aortobifemoral reconstruction, during which the
      aorta is clamped and the blood supply via the inferior mesenteric artery and
      iliac arteries is interrupted. The purpose of the present work was to study the
      catalytic activity concentration of phospholipase A2 and the mass concentrations
      of group I and group II phospholipases A2 in the sera of patients undergoing
      aortobifemoral reconstruction. Both the catalytic activity concentration of
      phospholipase A2 and the mass concentrations of group I and group II
      phospholipases A2 increased in serum samples after the operation. The catalytic
      activity concentration of phospholipase A2 correlated well with group II
      phospholipase A2 mass values (r = 0.81, p < 0.001), whereas no correlation was
      found between the catalytic activity concentration of phospholipase A2 and group
      I phospholipase A2 mass values (r = 0.12, p = 0.54). The results emphasize the
      role of group II phospholipase A2 in tissue injury after ischaemia and
      reperfusion.

PMID- 7578606
TI  - Determination of alkaline phosphatase isozymes in amniotic fluid.
AB  - A simple method for the determination of the three isozymes of alkaline
      phosphatase (EC 3.1.3.1) contained in amniotic fluid (fetal intestinal,
      placental, and liver-bone-kidney) is presented. Total alkaline phosphatase
      activity was assayed in 10,000 g supernatants of amniotic fluid from 30 normal
      women between the 16th and 20th week of pregnancy. Electrophoretic patterns and
      inhibition by L-phenylalanine and L-homoarginine studies showed that all the
      fetal intestinal isozyme was precipitated in the pellet after centrifugation at
      100,000 g for 90 min. Thus, the difference between total alkaline phosphatase
      activity and activity in the 100,000 g supernatant corresponds to fetal
      intestinal alkaline phosphatase. Placental isozyme can be determined by assaying
      alkaline phosphatase in the 100,000 g supernatant after heating at 56 degrees C
      for 90 min. Liver-bone-kidney isozyme activity is obtained by subtracting
      placental alkaline phosphatase activity from that of the 100,000 g supernatant.
      Mean percentages of the total alkaline phosphatase for each of the isozymes in
      amniotic fluid were 81% for fetal intestinal alkaline phosphatase, 7.5% for
      placental alkaline phosphatase and 12.0% for liver-bone-kidney alkaline
      phosphatase. Determination of fetal intestinal alkaline phosphatase by this
      method could be applied to the diagnosis of cystic fibrosis in fetuses having a
      1:4 risk of being affected.

PMID- 7578605
TI  - Identification of apolipoproteins A-I and B using high resolution electrophoresis
      on supported cellulose acetate.
AB  - A simple modification of high resolution electrophoresis on supported cellulose
      acetate is described. This modification is made by adding the surfactant Tween 20
      to the buffer and permits the identification of apolipoproteins A-I and B as well
      as the usually detected serum proteins. The procedure is reproducible using
      various supported cellulose acetate plates with manual and automated procedures.
      Furthermore, this improved high resolution electrophoresis allows the
      semiquantitative evaluation of these apolipoproteins both on freshly collected
      and on -20 degrees C stored serum samples.

PMID- 7578607
TI  - Evaluation of a first-line spectrophotometric screening test for increased faecal
      porphyrin concentration.
AB  - We compared a spectrophotometric screening test measuring faecal porphyrin
      concentration with an HPLC method. There was a good overall correlation between
      both methods although some scatter was observed. ROC plot analysis of the
      screening test leads to a cut-off value of 35 nmol porphyrin per g faeces, wet
      weight with a sensitivity of 97% and a specificity of 96%. These results indicate
      that the screening test is quite useful for detection of increased total faecal
      porphyrin concentration, but less useful in accurate measurement of increased
      total faecal porphyrin concentration.

PMID- 7578608
TI  - The influence of pH and various anions on the distribution of NH4+ in human
      blood.
AB  - The pH-dependent distribution of ammonia between blood cells and plasma was
      investigated with oxygenated blood samples from healthy subjects at 37 degrees C.
      Blood pH was varied between 6.95 and 7.65 by equilibration with different CO2
      mixtures. Plasma ammonia concentrations were measured directly with a specific
      enzymatic method. Ammonia concentrations within blood cells were calculated from
      a) the concentration changes of ammonia in plasma after addition of 87.7 mumol/l
      NH4Cl to whole blood and b) the pH-dependent haematocrit. The pH-dependency of
      the distribution ratio(ammonia) = P-ammonia/cell ammonia (substance
      concentrations in water spaces) is described by the equation distribution
      ratio(ammonia) = 3.095 - 0.342 x pHplasma (r = 0.928, n = 36) in good agreement
      with available literature data on the distribution of H+. A quantitative figure
      to describe the actual NH4+ concentration in oxygenated whole blood at defined
      values of P-NH4+, P-pH and haematocrit is given. Values of distribution
      ratio(ammonia) at pH 7.4 (0.57 or 0.75, ammonia concentrations corrected/not
      corrected for water content) are higher than those assumed so far in the
      literature. Addition of non-permeating anions (citrate, EDTA) to whole blood
      results in a shift of NH4+ from the intra- to the extracellular compartment. In
      contrast, chaotropic anions like iodide or thiocyanate lower distribution
      ratio(ammonia). To avoid medically important bias in the measurement of plasma
      ammonia concentration, the changes in pH or in the ionic composition of the blood
      sample following pretreatment with anticoagulants or preservatives should not
      exceed certain limits. Citrate is not a suitable anticoagulant.

PMID- 7578609
TI  - Evaluation of performance characteristics of automated measurement systems for
      allergy testing.
AB  - Reliability of test results, convenient handling and flexibility are major
      requirements on automated immunoassays systems. To investigate to what extent
      these requirements were met by the Pharmacia CAP and DPC IMMULITE and DPC
      Microplate Systems, we evaluated several performance characteristics of assays of
      specific IgE against some common inhalant allergens as well as the atopy tests
      Phadiatop (Pharmacia CAP System) and AlaTOP (DPC IMMULITE and Microplate System).
      Comparing Phadiatop and AlaTOP results (n = 95) to clinical data, the sensitivity
      was found to be 97% in the Pharmacia CAP System and 82% in the AlaTOP-DPC
      Microplate System and 88% with AlaTOP-IMMULITE. Specificity was in all cases
      higher than 90%. The pooled total variation was more than twice as high with the
      DPC Microplate System as compared to the Pharmacia CAP System in our first
      investigation. A second investigation showed similar values. The investigation of
      systematic differences showed that the error contribution of sample related
      differences between the systems was even larger and far exceeded the analytical
      variation. Thus the two methods do not seem to be measuring the same specific IgE
      antibodies. In 8 out of 8 cases with the Pharmacia CAP System positive and DPC
      negative results and in 2 out of 2 cases with DPC positive and Pharmacia CAP
      System negative results, the presence of IgE antibodies could be confirmed by IgE
      immunoblotting. Serum dilutions showed very irregular O/E patterns for the DPC
      Microplate System. There was no effect when adding non-specific IgE to serum
      samples. Addition of competing IgG antibodies showed a moderate decrease in
      binding of specific IgE in the Pharmacia CAP System when increasing amounts of
      IgG were added. The effect in the DPC Microplate System was more pronounced with
      large decreases, or increases of measured values even at lower concentration of
      the competing antibody. The results may indicate insufficient allergen
      concentration in the DPC assay and draw attention to the risk for undesirable
      complex formation between allergen and antibody in solution. The combination of
      the two DPC systems did not offer any advantages over Pharmacia CAP System from
      the handling or work flow point of view.

PMID- 7578610
TI  - Performance characteristics of different immunoassays for determination of
      parathyrin (1-84) in human plasma samples.
AB  - The performance characteristics of four radioisotopically and non
      radioisotopically labelled two-site immunoassays for the determination of
      'intact' parathyrin in plasma samples are reported. Within-run as well as between
      assay imprecision was characterized by coefficients of variation usually < 10%.
      Assessment of the linearity of dilution in plasma samples from patients with
      severe secondary hyperparathyroidism (obtained from patients with chronic renal
      failure prior to dialysis) revealed that an assay with N-terminal capture
      antibodies showed an increase of the values after dilution (p < 0.05) whereas
      another assay with C-terminal capture antibodies was characterized by a decrease
      of the values after dilution (p < 0.05). Correlation between the data obtained by
      the four assays and our currently used routine method (N-tact PTH from INCSTAR)
      revealed correlation coefficients of r > + 0.96 and slope values between 0.83 and
      1.34. Determination of the analytical recovery of parathyrin (1-84) from two
      reference materials [First International Reference Preparation 79/500 and
      synthetic human parathyrin (1-84)] revealed that the recovery rates were strongly
      influenced by (a) the assay employed for determination of parathyrin
      concentrations, (b) the matrix of the diluent and (c) the reference material
      used. These results as well as systematic differences between the assays we
      examined (employing plasma samples from unselected nephrological patients)
      require further efforts towards a more rigorous standardization of 'intact'
      parathyrin assays.

PMID- 7578611
TI  - Evaluation of the Hitachi 911 for routine urine analysis and for measurement of
      various special serum analytes.
AB  - The Boehringer Mannheim Hitachi 911 is a selective analyzer for 35 different
      methods including 3 ion-selective electrode (ISE) methods. We have evaluated this
      analyzer primarily to obtain objective information on its applicability for
      routine urine analyses in our laboratory. We also implemented appropriate assays
      for various special serum- and whole blood-tests, some for the first time on the
      Hitachi 911 and some with modified settings. Analytical evaluation involved NCCLS
      EP5-T2 (imprecision), NCCLS EP6-P (linearity), Krouwer 27 (multifactor) and
      Passing & Bablok (method comparison) evaluation protocols. With the exception of
      evidence of systematic erroneous sample predilution, overall results were
      favourable. Practicability of the Hitachi 911 was judged by simulating daily
      routine. During a period of two weeks, daily urine samples were rerun on the
      Hitachi 911, leading to a gain of about 50% in total processing time. It was
      concluded that the Hitachi 911 meets the requirements in terms of analytical
      performance, reliability, versatility and speed for an analyzer to be used in a
      routine (urine) setting, while having a distinct role in special (serum/whole
      blood) measurements.

PMID- 7578614
TI  - Reference limits of apolipoprotein A-I and apolipoprotein B using an IFCC
      standardized immunonephelometric method.
AB  - An important collaborative study organized by the IFCC enabled the selection of
      international reference materials and the standardization of commercially
      available methods by the use of common calibrators. In this paper, we report the
      reference limits of apolipoprotein A-I and apolipoprotein B in a selected healthy
      French population. The apolipoprotein measurements were performed on BNA Behring
      using reagents and protocols supplied by the manufacturer: the standard sera were
      calibrated using the IFCC-WHO reference preparations (SP1 and SP3). In addition,
      the apolipoprotein B protocol was modified by the addition of a supplementary
      reagent to reduce the interference by lipaemic samples on immunonephelometric
      measurement. In a sample of 115 random serum samples, there was a decrease in
      mean concentration between non-standardized and standardized methods: -4.8% for
      apolipoprotein A-I and -4.7% for apolipoprotein B. The reference limits for
      apolipoprotein A-I are unaffected by gender between 4 and 14 years, thereafter
      vary with age and gender until 40 years and with gender alone between 40 and 60
      years. For apolipoprotein B, the variation with gender is only significant
      between 30 and 49 years.

PMID- 7578613
TI  - Cyclic AMP-related and cation-affected human platelet chloride transport
      regulation.
AB  - Cystic fibrosis has been characterized as a defect in the regulation of cyclic
      AMP-dependent transepithelial chloride transport. The activation of cyclic AMP
      dependent protein kinase A by cyclic AMP occurs normally in cystic fibrosis
      cells, but they fail to transport chloride ions in response to protein kinase A
      stimulation. Defective chloride secretion and abnormal electrolyte transport
      occurs in several organs including the lung, sweat glands, intestine and
      pancreas. The present work was aimed at exploring whether the same or similar
      regulatory systems are functional in platelets, and if they are altered or
      deficient in individuals with cystic fibrosis. Chloride transport in platelets
      from normal subjects and from cystic fibrosis patients was measured by cell
      sizing techniques where chloride permeability is the limiting factor. In
      platelets from healthy volunteers, the chloride channel blocker, 5-nitro-2-(3
      phenylpropylamino) benzoic acid, inhibits the transport in a dose-dependent
      manner. The preservation of chloride transport capability is shown to be
      dependent upon the presence of either Ca2+ or two divalent cation substitutes,
      Cd2+ or Cu2+. It is also shown that in normal subjects 0.1 mumol/l prostaglandin
      E1, which elevates cyclic AMP 6 times and abolishes platelet aggregation,
      significantly enhances the rate constant of the transport. Furthermore, in five
      out of nine cystic fibrosis patients studied, platelet chloride transport did not
      respond to stimulation by prostaglandin E1.

PMID- 7578615
TI  - An improved method for determination of thiocyanate in plasma and urine.
AB  - An improved spectrophotometric method is described for the determination of
      thiocyanate in plasma and urine. Thiocyanate is adsorbed on a weak anion-exchange
      resin with strong affinity for chaotropic ions, and eluted with perchlorate.
      Thiocyanate is then chlorinated by hypochlorite and quantified according to the
      Konig (J Prakt Chem 1904; 69:105-37) reaction by use of isonicotinic acid and 1,3
      dimethyl-barbituric acid. The method affords a simple, rapid and sensitive assay
      for thiocyanate and has a detection limit of 0.93 mumol/l. At thiocyanate
      concentrations of 107.1 and 167.4 mumol/l in plasma and urine the within-day CVs
      were 0.69% and 1.1% respectively, and the total imprecision measured for a period
      of 65 days was 0.98%. Analytical recoveries were quantitative both with urine and
      plasma samples.

PMID- 7578612
TI  - Skin burn injury and oxidative stress in liver and lung tissues of rabbit models.
AB  - The effects of burn injury (30% of total body surface area) on the levels of
      oxidized and reduced glutathione, malondialdehyde, and on the activities of
      certain glutathione-dependent enzymes, have been determined in tissues of rabbit
      models. Thus, the malondialdehyde, glutathione (GSH), glutathione disulfide
      (GSSG) concentrations and the specific activities of glutathione peroxidase,
      glutathione S-transferase, and glutathione reductase were measured in liver and
      lung of 24-h burn rabbit models and compared to the corresponding values in 24-h
      sham burn (medicated, anesthetic/analgesic) rabbit models. It was found that the
      concentrations of malondialdehyde in liver and lung of burn models were increased
      by 17% and 29% respectively. Glutathione concentrations were decreased by 29% in
      liver and 13% in lung, and glutathione disulfide concentrations were increased by
      35% in liver and 33% in lung, in burn versus sham burn models. It was also found
      that the specific activities of glutathione peroxidase decreased significantly,
      resultant to burn injury, by an average of 35% and 27% in liver and lung,
      respectively. Burn injury also decreased glutathione S-transferase specific
      activities by 14% in liver and 23% in lung tissues. In contrast, glutathione
      reductase specific activity was increased in liver tissues (22%), but was
      decreased (19%), as with the other enzymes studied, in lung tissues of burn
      models. Control model studies (no medication, no sham burn) show that these
      effects of burn injury are additional to effects elicited by medication
      associated with sham burn models. The data of this study are indicative of a
      major oxidative stress in liver and lung tissues due to burn injury at a remote
      site.

PMID- 7578617
TI  - Measurement of free magnesium in blood, serum and plasma with an ion-sensitive
      electrode.
AB  - The fraction of total magnesium bound to protein and other substances depends
      upon the pH. pH-dependency of ionized free magnesium (iMg2+) in serum is
      expressed by the Siggaard-Andersen equation: iMg2+ (pH) = iMg2+ (7.4) x 10x(7.4 -
      pH). During preparation of serum or plasma, considerable pH changes occur which
      have to be corrected on the basis of the above mentioned equation. For pH
      correction of iMg2+, x < 0.1 has so far been used. However, this is correct only
      for new Mg(2+)-sensitive electrodes. During the lifetime of Mg2+ electrodes used
      in the "Microlyte Magnesium" (Kone Instruments, Finland) x increases and x = 0.2
      was found to be a suitable approximation for most of the lifetime. By
      instantaneous iMg2+ measurements in whole blood samples pH changes and the
      uncertainty of x can be avoided. Dilution of blood by intravenous infusions
      decreases x nearly proportionally to the decrease of protein concentration in
      blood. Various methodological influences such as temperature and delay time
      before centrifugation, storage of serum and venous occlusion were studied. The
      circadian rhythm of iMg2+ was found to be considerably more pronounced than that
      of total Mg and was negatively correlated to changes of free fatty acids. To
      avoid variations of iMg2+ due to circadian changes, blood collection should be
      carried out between 6 and 10 a.m. The normal range of iMg2+ in blood of 179
      healthy subjects was found to be between 0.46 and 0.60 mmol/l and the quotient of
      free and total Mg between 0.59 and 0.71. The accuracy of "Microlyte Magnesium"
      (Kone Instruments, Finland) is sufficient in a wide range of iMg2+.

PMID- 7578616
TI  - Exclusion of acute myocardial infarction. The value of measuring creatine kinase
      slope.
AB  - For the exclusion (and diagnosis) of acute myocardial infarction, we studied
      timed sequential (slope) measurements of creatine kinase and creatine kinase-MB
      catalytic activity concentration, creatine kinase-MB mass concentration, troponin
      T and myoglobin, using data from 242 patients consecutively admitted for
      evaluation of suspected acute myocardial infarction in the 12 hours before
      admission. Three biochemical strategies based on measurements in two consecutive
      samples obtained within 12 hours after admission were evaluated. The highest
      sensitivities were encountered for a biochemical strategy based on the sole
      measurement of creatine kinase mass concentration (98%) or troponin T (96%) and a
      strategy based on measurements of creatine kinase activity concentrations, which
      includes creatine kinase slope calculation and measurement of creatine kinase
      mass concentration (95%). Both strategies were applied in subgroups of patients
      based on the electrocardiographic findings. In patients with a normal
      electrocardiogram, the sensitivity of the strategy using sole measurements of
      creatine kinase mass concentration was 100%, but this was true for the strategy
      based on creatine kinase slope measurements, which is the cheaper and therefore
      preferred procedure for excluding myocardial infarction. This approach, however,
      does not account for detecting minor myocardial cell damage in patients not yet
      fulfilling the criteria of the World Health Organization for diagnosing acute
      myocardial infarction.

PMID- 7578619
TI  - The analytical and clinical performance of the new Boehringer Mannheim Enzymun
      Test PSA assay for prostate-specific antigen.
AB  - A combined evaluation effort of the Boehringer Mannheim Research and Development
      and Evaluation Departments and the University Hospital Rotterdam is described
      regarding the new, fully automated Enzymun-Test PSA assay for prostate-specific
      antigen. The study consisted of an analytical and a clinical part. At both sites,
      the vast majority of intra-assay coefficients of variation ranged from 2 to 3%
      above prostate-specific antigen = 1 microgram/l. Below that concentration higher
      coefficients of variation were measured. Comparable results were obtained for the
      interassay imprecision. The analytical sensitivity (lower limit of detection) was
      found to be 0.02 microgram/l at both sites. Regarding the linearity of the assay
      no systematic drift to either elevated or lower values which increasing dilution
      was found. Deviations remained well in the range between 100 +/- 10%. The
      correlation with the Abbot IMx PSA assay as performed with a large set of
      clinical specimens revealed: y (= Enzymun) = 1.16x (= IMx) + 0.0; r = 0.985; n =
      245. In this comparison study small differences between benign prostatic
      hyperplasia patients and prostate cancer patients were detected, perhaps partly
      based on the differences in recognition patterns of various molecular prostate
      specific antigen forms in both assays. A follow-up after radical prostatectomy
      with 17 patients (50 serum samples) also showed a good comparability between the
      Enzymun-Test and the IMx assay. The limited check of the reference range resulted
      in data comparable to what can be found in the literature: out of 100 samples
      originating from healthy males, aged 20-60 years, 99 had prostate-specific
      antigen values lower than 4 micrograms/l. Based on our findings it can be
      concluded that the new Enzymun-Test PSA assay meets the current state-of-the-art
      criteria in prostate-specific antigen methodology.

PMID- 7578618
TI  - Multicentre evaluation of a non-wipe system for the rapid determination of total
      cholesterol in capillary blood, Accutrend Cholesterol on Accutrend GC.
AB  - Accutrend Cholesterol, a non-wipe test for the determination of total cholesterol
      in capillary blood, was evaluated at four clinical centres. Cholesterol
      determinations with the Accutrend system using capillary blood were compared with
      results obtained with the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method
      using the respective capillary sera. Triacylglycerols, uric acid and haematocrit
      were determined to evaluate potential interference. Imprecision measurements were
      performed with venous blood. To examine the reproducibility of results from lot
      to lot, three different lots of test strips were included in these
      investigations. Results with Accutrend Cholesterol agree with those of the
      comparison method within systematic differences of +2.5% to -3.2%, depending on
      the lot. There was no interference by triacylglycerols up to 10.28 mmol/l (900
      mg/dl), by uric acid 60 to 400 mumol/l (1 mg/dl to 7 mg/dl), or by haematocrits
      between 0.35 and 0.54. Impression data show coefficients of variation of
      generally less than 5%. Thus Accutrend Cholesterol proved to be a reliable system
      for the determination of total cholesterol.

PMID- 7578620
TI  - Quality and accreditation systems in clinical biochemistry in the European Union.
AB  - The European Community Confederation of Clinical Chemistry (EC4) formed in Nice
      in April 1993 has established a working group on laboratory accreditation. The
      aim of the group is to explore the possibilities for harmonisation of
      accreditation and quality systems in clinical laboratories in the European
      Community (EC). It is felt essential that professions should play a key role in
      the process, and that the principle of subsidiarity should be observed in
      relation to implementation and organisation in individual member states. The
      first task has been to collect information concerning such systems. In September
      1993 a questionnaire was distributed to the twelve IFCC related societies for
      clinical chemistry in the EC. By December 1994 eleven societies had responded.
      The questionnaire related to the existence or planned introduction of quality and
      accreditation systems, the basis of the standards used and requirements for
      analytical aspects and qualifications of staff as well as professional aspects.
      Questions also addressed the way in which inspection were organised, the
      selection and training of inspectors, the organisation of systems and what
      interest there was in harmonisation. The results of this study are presented in
      this paper.

PMID- 7578621
TI  - International Federation of Clinical Chemistry (IFCC), Committee on pH, Blood
      Gases and Electrolytes: approved IFCC recommendation on definitions of quantities
      and conventions related to blood gases and pH.
AB  - Terminology in blood pH and gas analysis can be confusing, both because more than
      one name has been used for the same quantity, and because the same name has been
      used for more than one quantity. In addition, several calculated quantities are
      commonly used, but in some cases many different algorithms have been published
      for a single quantity. This document contains definitions of the most useful
      quantities in blood pH and gas analysis, and presents algorithms for the most
      useful calculated quantities. Use of these should lessen confusion among users
      and should also result in data that are more comparable among laboratories.

PMID- 7578622
TI  - Cooperation between transcription factors regulates liver development.
AB  - Characterization and cloning of liver-enriched transcription factors have
      provided the tools to study the regulation of liver differentiation.
      Characterization of the temporal and spatial expression of these factors have
      shown a sequential order of appearance, in coordination with the expression of
      their target genes, during liver development. Evidence has accumulated showing
      cooperation between distinct factors in regulating liver-specific gene
      expression. Since each of these factors is not uniquely expressed in the liver,
      yet, the liver is the only tissue that expresses all of these factors, the
      cooperation between the coexisting liver-enriched factors could constitute the
      basis for the regulation of liver-specific gene expression.

PMID- 7578624
TI  - Monoamine neurotransmitters and metabolites in the cerebrospinal fluid following
      perinatal asphyxia.
AB  - While the release of neurotransmitters is involved in the pathophysiology of
      brain damage following birth asphyxia, it also plays a role in endogenous defense
      against such damage. Levels of monoamines and the main cerebral monoamine
      metabolites in the cerebrospinal fluid (CSF) were measured in asphyxiated and
      control infants within 24 h after birth. The results indicate an increased
      turnover of noradrenaline (NA) and dopamine following asphyxia. Furthermore, the
      NA stores in the brain seem to be exhausted in some cases. We conclude that this
      increase in catecholamine turnover to some extent explains the clinical symptoms
      of hypoxic-ischemic encephalopathy and that it may reflect an intrinsic adaptive
      capacity to perinatal distress.

PMID- 7578623
TI  - Responsiveness to the odour of amniotic fluid in the human neonate.
AB  - Two-day-old newborns were videotaped during a double-choice test contrasting the
      odours of their amniotic fluid (AF) and of a control stimulus. To control for
      early motor asymmetries, the lateral position of both stimuli was balanced both
      between and within subjects. On average, neonates oriented their nose for a
      significantly longer duration toward the odour of AF. Regardless of the nature of
      the stimulus, neonates also evinced a marked head-turning bias to the right side.
      The nature of the odour stimulus and side of presentation interacted so that
      infants turned their nose longer to the AF odour when it was presented from the
      right side. These data indicate that newborns can detect the AF odour, and that
      they remain attracted towards it for at least 2 days after birth.

PMID- 7578625
TI  - Influence of early feeding mode on body composition of infants.
AB  - To determine the effect of infant feeding mode on body composition, a cross
      sectional study was designed in which 10 breast-fed and 10 formula-fed infants
      were studied at 1 month of age, and another 10 breast-fed and 10 formula-fed
      infants at 4 months of age. Anthropometric measurements included body weights,
      lengths, selected diameters, circumferences and skinfold thicknesses. Total body
      water (TBWO) was measured by 18O dilution. A dose equivalent to 300 mg 18O/kg
      body weight was administered orally to the infants. Fat-free mass (FFMO) was
      calculated from TBWO using reference hydration constants of 0.805 and 0.798 at 1
      and 4 months, respectively. Body fatO was taken as the difference between weight
      and FFMO. Total-body electrical conductivity (TOBEC) measurements were used to
      estimate FFMT and FATT. ANOVA was used to analyze the anthropometric and body
      composition data using feeding mode and age as grouping factors. Anthropometric
      measurements did not differ by feeding mode. TBW (kg) and FFM (kg) and body fat
      (kg) derived from 18O dilution or TOBEC did not differ by feeding mode. TBWO,T
      (%wt), FFMO,T (%wt), and body fatO,T (%wt) derived from 18O dilution and TOBEC
      differed significantly between the breast-fed and formula-fed infants at 4 months
      of age (p < 0.05). Expressed as a percentage of body weight, TBWO and FFMO,T were
      higher and body fatO,T was lower among the 4-month formula-fed infants.

PMID- 7578627
TI  - Ethanol, morphine and barbiturate alter the hemodynamic and cerebral response to
      cocaine in newborn pigs.
AB  - Newborns delivered to cocaine-abusing mothers are often exposed to other
      concurrently consumed illicit drugs, which may alter the hemodynamic and cerebral
      response to cocaine. This study examined the interaction of ethanol, morphine or
      barbiturate with cocaine on mean arterial pressure (MAP), cerebral blood flow
      (CBF) and cerebral metabolic rate of oxygen (CMRO2) in newborn pigs. CBF, CMRO2
      and cerebral O2 extraction (CEO2) were measured before and 4 and 10 min after
      cocaine (1.5 mg/kg i.v.) was administered in piglets that were awake, or
      pretreated with morphine, ethanol or pentobarbital. In awake piglets, cocaine
      increased CMRO2 and CEO2 while it had no significant effect on CBF. Conversely,
      in morphine- and ethanol-pretreated piglets, cocaine decreased CMRO2, decreased
      CBF and had not effect on CEO2. In awake piglets, cocaine increased MAP, whereas
      in morphine- or ethanol-pretreated piglets, cocaine decreased MAP. In the
      pentobarbital group, cocaine had no effect. These data demonstrate that other
      drugs of abuse alter the hemodynamic and cerebral effects of cocaine in the
      immature animal and may contribute to the central nervous system abnormalities in
      'crack babies'.

PMID- 7578626
TI  - Effect of nordihydroguaiaretic acid on cerebral blood flow and metabolism during
      hypoxia in newborn piglets.
AB  - Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was investigated for
      its effect on cerebral blood flow (CBF) and cortical oxygen consumption during
      hypoxia in 9 anesthetized, ventilated newborn piglets. CBF was measured by
      radioactive microspheres while brain cortical metabolism was evaluated by
      continuous 31P-NMR spectroscopy. Five piglets were treated with NDGA (3 mg/kg
      i.v. in 50% ethanol as vehicle) prior to hypoxia and had CBF measured before NDGA
      (control), 15 min after NDGA (baseline) and then after 15 and 45 min of hypoxia
      following NDGA. Another 4 piglets were treated with vehicle (2 ml/kg 50% ethanol)
      under the same protocol. In the NDGA-treated piglets, cerebral cortical O2
      consumption for a given PCr/Pi was significantly increased (p < 0.05) compared to
      non-NDGA. Since NDGA inhibits production of vasoconstricting leukotrienes during
      hypoxia, cortical capillary beds otherwise constricted may be perfused following
      NDGA, thus increasing the O2-consuming tissue area.

PMID- 7578629
TI  - Failure of immunoglobulins to prevent neonatal thrombocytopenia in mothers with
      immunothrombocytopenic purpura.
AB  - We report the case of a full-term (gestational age: 39 weeks) female newborn of a
      mother affected by immunothrombocytopenic purpura, treated with a high total dose
      (2 g/kg) of intravenous IgG, administered over a 3-day period starting 3 days
      before delivery. Infant platelet count at birth was 20,000/mm3 and she showed a
      great number of petechiae on the first day of life. After a random donor platelet
      transfusion and treatment with intravenous high-dose IgG (400 mg/kg for 5 days),
      platelet count began to increase. We conclude that exogenous IgG, even at high
      concentrations, apparently does not significantly cross the placenta, despite
      adequate maternal blood levels.

PMID- 7578630
TI  - Ascorbic acid concentrations in umbilical cord veins and arteries of preterm and
      term newborns.
AB  - Ascorbic acid (AA) is a powerful antioxidant required for the defense against
      oxidative stress. At present it is not known whether AA may play a role in the
      developmental process of the fetus. We therefore determined the relationship of
      AA levels between the umbilical cord vein (UCV) and umbilical cord artery (UCA)
      of preterm ( < 37 weeks of gestation) and term ( > or = 37 weeks of gestation)
      infants and compared those levels to matched maternal venous AA levels. We also
      assessed the association between UCV plasma AA levels with birth weight and
      gestational age by measuring AA in 88 UCV plasma samples and 58 UCA plasma
      samples obtained from newborn infants ranging in gestational age from 24 to 42
      weeks and birth weight from 675 to 5,020 g, by high pressure liquid
      chromatography. Maternal venous samples were collected at the time of delivery.
      The mean UCV plasma AA levels (mg/dl) were significantly lower in the preterm
      group than in the term group (0.43 +/- 0.59 and 1.16 +/- 0.97, respectively; p <
      0.002); however, the mean UCA plasma AA levels did not differ between the groups.
      In contrast, mean maternal venous plasma AA levels of the preterm group (1.33 +/-
      0.62) were significantly higher than those of the mothers in the term group (0.72
      +/- 0.69; p < 0.01). A direct correlation was found between UCV levels and birth
      weight (r = 0.23, p < 0.05), and UCV levels and gestational age (r = 0.23, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578628
TI  - Signaling pathways regulating ornithine decarboxylase activity in the embryonic
      chicken.
AB  - The pathways regulating ornithine decarboxylase (ODC) activity in the chick
      embryo were studied to determine which kinase-signaling pathways regulate ODC
      activity levels during development. Insulin-dependent tyrosine kinase, protein
      kinase C and cAMP-dependent protein kinase were activated by the addition of
      insulin, tetradecanoylphorbol-12,13-acetate, and forskolin, respectively. All
      three drugs increased ODC activity and forskolin combined with insulin increased
      ODC activity above the increase caused by either drug alone. These results
      suggest that all three signaling pathways regulate ODC activity during
      development and that common intermediates exist among the pathways downstream of
      the kinases.

PMID- 7578632
TI  - Phagocytosis-promoting factor in human colostrum.
AB  - The effect of colostrum of mothers of preterm and full-term newborns on the
      phagocytic activity for latex particles by normal peripheral blood
      polymorphonuclear cells was examined. The results showed that human colostrum
      contains a phagocytosis-promoting factor(s), which not only increases the number
      of phagocytic cells, but also stimulates the phagocytic activity of the
      individual cell. This factor(s) was more active in preterm colostrum. Thus, while
      term colostrum increased the number of phagocytic cells by 95% in comparison with
      the control, preterm colostrum enhanced the number of phagocytic cells by 300%.
      Similarly, term colostrum increased the phagocytic capacity of the individual
      cell by 51%, whereas preterm colostrum by 137%. The difference between the
      results in all experimental points was statistically highly significant.

PMID- 7578633
TI  - Hepatic biotransformation capacity in low-birth-weight infants as measured with
      the [15N]methacetin urine test: influences of gestational age, postnatal age, and
      intrauterine growth retardation.
AB  - The influences of the gestational age (range: 28-36 weeks) and the postnatal age
      (range: 6-100 days) on the biotransformation capacity of the liver were studied
      in 51 preterm appropriate-for-gestational-age infants and in 20 preterm small-for
      gestational-age infants using the [15N]methacetin urine test. Methacetin is a
      test drug assessing a two-step pathway of biotransformation including
      monooxygenation and conjugation. After oral administration of 3 mg
      [15N]methacetin/kg body-weight, the cumulative 15N excretion in urine during the
      consecutive 9 h was measured and used as a marker of microsomal biotransformation
      capacity. In preterm appropriate-for-gestational-age infants, the
      biotransformation capacity increases with gestational age as well as with
      postnatal age, but the strongest correlation could be found between cumulative
      [15N] excretion and postmenstrual age. Intrauterine growth retardation results in
      lower biotransformation capacity (26.3 +/- 11.3 vs. 36.1 +/- 9.6% [15N]
      excretion, expressed as percentage of intake) and disturbed postnatal development
      of this hepatic function. The data indicate that normal intrauterine development
      is a prerequisite for normal postnatal development of the biotransformation
      capacity, which might have consequences for the metabolism and efficacy of
      certain drugs in small-for-gestational-age infants.

PMID- 7578631
TI  - Maternal and neonatal plasma transthyretin (prealbumin) concentrations and birth
      weight of newborn infants.
AB  - Animal studies have shown that maternal protein deficiency during pregnancy
      affects fetal birth weight. This study has examined whether or not the fetal
      birth weight of full-term newborns has any relationship with the acute protein
      nutrition status of the mother. Protein nutrition status was assessed by
      measuring the plasma transthyretin (prealbumin) concentrations. Plasma
      transthyretin concentrations (mean +/- SE) from the cord blood of 20 newborns
      (10.9 +/- 0.5 mg/dl) were significantly lower (p < 0.000000001) compared with
      respective maternal concentrations (17.8 +/- 0.8). There was a significant
      correlation of transthyretin concentrations between mother and newborns (r =
      0.61, p < 0.005), and of newborn birth weight with plasma transthyretin
      concentrations of newborns (r = 0.57, p < 0.01) and mothers (r = 0.51, p < 0.03).
      This study documents a relationship of fetal birth weight with maternal and
      newborn plasma transthyretin concentrations.

PMID- 7578634
TI  - Effects of epidermal growth factor on glucose metabolism in neonatal rats.
AB  - Epidermal growth factor (EGF) may play a key role in fetal growth. We have
      investigated the effects of EGF on glucose metabolism, the main source of energy
      during the early neonatal period. When compared to control, EGF treatment
      increased hepatic glycogen, plasma insulin, and the proportion of B cells in the
      islets of Langerhans, but decreased the concentration of plasma glucagon. Thus,
      the insulin-to-glucagon molar ratio in plasma was increased in the EGF-treated
      group. These data suggest that EGF shifts glucose metabolism from catabolism
      towards anabolism during the early neonatal period by controlling the pancreatic
      endocrine system. This effect may help the neonate in adapting to the
      extrauterine environment after birth.

PMID- 7578635
TI  - Effects of methamphetamine on rat embryos cultured in vitro.
AB  - Wistar rat embryos were explanted on day 10.5 of gestation and exposed in vitro
      to methamphetamine (MAMP) at a concentration of 0.1, 0.2, 0.4, 0.6, or 0.8 mM for
      24 h, and the direct teratogenic effects of the drug on rat embryos were
      examined. The viability of cultured embryos was not affected by the MAMP
      treatment. The yolk sac diameter was reduced at MAMP concentrations of 0.6 and
      0.8 mM. The crown-rump length and the somite number of the embryos decreased
      significantly and dependently on the MAMP concentrations at 0.4-0.8 mM. The
      protein content was also significantly reduced at 0.4-0.8 mM. The developmental
      score was decreased in a concentration-dependent manner. The frequency of
      malformed embryos significantly increased at 0.6 and 0.8 mM. The malformations
      induced in treated embryos included microcephaly, neural tube defects, incomplete
      rotation of the body axis, and tortuous spinal cord. Abnormal histological
      changes such as derangement and necrosis in the neuroepithelial tissue were
      observed in embryos exposed to high concentration of the drug. Our results
      revealed the direct embryotoxic and teratogenic effects of MAMP in the rat.

PMID- 7578636
TI  - Effects of maternal administration of dexamethasone and thyrotropin-releasing
      hormone on fetal rat pulmonary surfactant synthesis.
AB  - To determine the effects of maternal administration of dexamethasone (DEX) and
      thyrotropin-releasing hormone (TRH) on fetal lung maturation, 16 pregnant rats
      were divided into the following four groups: 20 micrograms/kg TRH twice a day was
      given intraperitoneally to the TRH group rats, 0.5 mg/kg/day DEX to the DEX group
      and both DEX and TRH to the DEX + TRH group for 3 consecutive days from
      gestational day 17. The control rats were given an equivalent volume of saline.
      The pregnant rats were sacrificed on gestational day 20 and the fetal lungs were
      removed. The relative amounts of surfactant protein A (SP-A), B (SP-B) and C (SP
      C) mRNAs were analyzed by Northern blotting and the total lung disaturated
      phosphatidylcholine (DSPC) contents were determined using an enzymatic method.
      The SP-B and -C mRNA and DSPC contents in the DEX and DEX + TRH groups were
      significantly higher than those in the control group, whereas the SP-A mRNA
      levels did not differ significantly among the four groups. The SP-B and -C mRNA
      and DSPC contents in the DEX and DEX + TRH groups did not differ significantly.
      These findings suggest that TRH has no effects on the regulation of surfactant
      protein mRNAs or DSPC contents in the fetal rat lung and has no additive effects
      when combined with DEX.

PMID- 7578637
TI  - Dendritic branching of claustral neurons in neonatally undernourished rats.
AB  - Golgi-Cox-impregnated neurons of the claustrum were studied in control and
      undernourished Wistar strain rats at 12, 20, and 40 days of age. A reduced cross
      sectional somatic area was observed in the 20-day-old undernourished rats and a
      significant reduction in the dendritic area was observed in the three ages
      studied. Dendritic arbor alteration was mainly observed in the number of high
      order and in the total number of dendritic branches of undernourished rats
      throughout the study. The data suggest vulnerability of the dendritic claustral
      growth process during the postnatal period to neonatal undernutrition. These
      alterations may be associated with telencephalic integrative impairments
      described in perinatal undernourished rats.

PMID- 7578639
TI  - Effects of porcine growth hormone on pregnancy and fetal/neonatal development in
      the rat.
AB  - Porcine growth hormone was given subcutaneously twice daily to two groups of 20
      females at dose levels of 0.5 and 2.5 IU/kg (1 and 5 IU/kg/day). A control group
      of 20 females was similarly treated with vehicle. The females were given either
      vehicle or porcine growth hormone from gestation day (GD) 6 through GD 21, for 10
      females that were cesarean sectioned, or through lactation day (LD) 21, for 10
      females scheduled for natural delivery. There were no deaths, abortions, or drug
      related physical signs in any treatment group. Drug-related effects during
      gestation were limited to significant (p < or = 0.05) pharmacologically mediated
      increases in F0 maternal body weight gain during GD 6-20 in the 2.5-IU/kg group,
      approximately 24% above controls. During LD 0-21, there were significant (p < or
      = 0.05) dose-related increases in average maternal body weight gain in the 0.5-
      and 2.5IU/kg groups (72 and 200% above controls, respectively). Consistent with
      these findings, there were dose-dependent increases in maternal serum growth
      hormone and IGF-1 levels noted on GD 21 and LD 21 in both drug-treated groups.
      There were no drug-related effects on embryonal/fetal survival, GD 21 fetal body
      weight, placental weight, fetal femur length and width, or fetal morphology as
      determined by external, visceral, and skeletal examinations. There were no drug
      related effects on F1 pup mortality, physical signs, body weight, biparietal
      diameter, liver weight, and femur length or width. These data suggest that
      subcutaneous administration of growth hormone to pregnant and lactating rats, at
      a dose that produces significant (p < or = 0.05) increases in maternal body
      weight gain and serum IGF-1 levels, has no apparent effect on embryonal/fetal
      development or preweaning growth.

PMID- 7578638
TI  - Serum amino acid concentrations in growing rats fed intact protein versus
      enzymatic protein hydrolysate-based diets.
AB  - The aim of this study was to evaluate the effect of the molecular form of dietary
      protein (native or enzymatically hydrolyzed) on the total serum protein
      concentrations and the serum amino acid profile of growing rats at weaning.
      Wistar male rats at weaning were randomly assigned to one of the four isocaloric
      and isonitrogenous (12% protein equivalent content) diets and fed for 7 days. The
      protein sources of the diets were: whey protein, casein and their respective
      hydrolysates. Differences in the serum amino acid profiles exclusively related to
      the amino acid composition of the protein (casein or whey proteins) were
      observed, but differences due to their molecular form were not observed. It is
      concluded that the use of enzymatic hydrolysates of whey proteins and casein has
      the same effects as their native proteins on nitrogen intake, body weight gain
      and serum amino acid profile of growing rats at weaning.

PMID- 7578640
TI  - The piglet as a model for cerebral circulation: an angiographic study.
AB  - The aim of this study was to further investigate the possibilities and
      limitations of the newborn piglet as a model for neonatal cerebral circulation
      and injury. The precerebral and cerebral circulation was visualized by aortic
      arch contrast injection and selective injections into internal carotid and
      vertebral arteries. Due to the well-developed collateral circulation, it is not
      possible to produce severe focal cerebral ischemia in the piglet by ligation of
      extracranial arteries. It is possible to produce a modified common carotid artery
      which supplies mainly intracerebral tissues and is accessible for continuous
      measurements of cerebral blood flow.

PMID- 7578642
TI  - Decreased dopamine uptake into platelet storage granules in Gilles de la Tourette
      disease.
AB  - The movement disorder of Gilles de la Tourette (GdlT) disease may reflect
      hyperactivity of the basal ganglionic dopamine system. Since platelets have been
      suggested as peripheral models for the study of catecholamine neurons, we
      developed a method to measure the uptake of [3H]-DA into platelet storage
      granules (PSG). In the present report, PSG were incubated with [3H] DA, and Vmax
      and Km values were calculated by linear regression analysis (Lineweaver Burke
      plot). The uptake of DA (0.5-5 microM) by PSG from 18 GdlT patients was
      significantly lower (p < .0001) compared to 15 controls (Vmax mean +/- SD, 107.5
      +/- 42.5 and 265.3 +/- 66.5 fmole/mg protein resp.). The decrease of DA uptake in
      GdlT may reflect compensatory presynaptic changes that reduce DA activity.

PMID- 7578641
TI  - Modifiability of neuropsychological dysfunction in schizophrenia.
AB  - Schizophrenia is often characterized by compromised neuropsychological
      functioning, especially on tasks sensitive to frontal and temporohippocampal
      functions but the extent to which cognitive dysfunction can be modified in
      schizophrenics remains unclear. Twenty-four inpatient schizophrenics and 24
      intellectually and demographically matched, inpatient mood-disordered controls
      were randomly assigned to one of two conditions. Subjects assigned to the cued
      condition received instructional cues on measures of visual and semantic memory,
      executive function, and constructional ability. Subjects in the standard
      condition performed the same neuropsychological measures without cues. The
      present study revealed some degree of plasticity of neurobehavioral function in
      schizophrenia.

PMID- 7578643
TI  - A case of bipolar disorder with balanced chromosomal translocation.

PMID- 7578644
TI  - Melatonin treatment of a non-24-hour sleep-wake cycle in a blind retarded child.

PMID- 7578645
TI  - Drug screening in "normal" controls.

PMID- 7578646
TI  - Acute effect of exercise on human blood platelet serotonin uptake and monoamine
      oxidase activity.

PMID- 7578647
TI  - Serial dexamethasone suppression tests by measuring urinary cortisol among
      rapidly cycling patients.

PMID- 7578648
TI  - Osteoporosis and schizophrenia: can we limit known risk factors?

PMID- 7578649
TI  - Phasic asymmetries in phasic affective disorders.

PMID- 7578650
TI  - Magnetic resonance imaging evaluation of brain iron levels.

PMID- 7578652
TI  - Elmer Ernest Southard 1876-1920.

PMID- 7578654
TI  - White matter signal hyperintensities in the brains of patients with late
      paraphrenia and the normal, community-living elderly.
AB  - We determined the prevalence and anatomical location of areas of white matter
      hyperintensity visualized by magnetic resonance imaging in the brains of 38 late
      paraphrenic patients with an onset of psychotic illness after the age of 60 and
      31 healthy aged community volunteers. All degrees of white matter signal
      hyperintensity were very common in both groups, and there was no excess of such
      changes in the brain of patients. Periventricular white matter and subcortical
      grey matter hyperintensities were significantly associated with both measured
      diastolic and systolic blood pressure in patients and control subjects.
      Periventricular and deep white matter, together with subcortical grey matter
      hyperintensities, were significantly associated with increased age. The excess of
      such presumed brain-imaging abnormalities previously reported in patients with an
      onset of psychosis late in life may be a consequence of earlier authors' failure
      to include examination of appropriate community control populations and to
      carefully exclude patients with evidence of stroke.

PMID- 7578651
TI  - Buprenorphine for human immunovirus-positive opiate-dependent patients.

PMID- 7578655
TI  - Human oculomotor function: reliability and diurnal variation.
AB  - To provide information on test-retest reliability for seven oculomotor paradigms
      currently used in studies of schizophrenia and other neuropsychiatric conditions,
      we tested eight controls at four weekly intervals, twice in the morning (8-10 AM)
      and twice in the afternoon (3-5 PM). Intraclass correlation coefficients were
      significant (p < .05) for both AM and PM pairs of measures as well as for mean AM
      and PM pairs for closed-loop pursuit gain, open-loop pursuit gain (using velocity
      as the measure), saccadic frequency during pursuit and fixation, visually and
      nonvisually guided saccadic latency and velocity, antisaccadic latency, and
      premature reflexive saccades during the memory-guided saccade task. Acceleration
      as a measure of open-loop gain (for slower targets) and accuracy of saccades to a
      moving target were only reliable at PM testing time. Nonvisually guided saccadic
      accuracy and inappropriate reflexive saccades during the antisaccade task were
      not reliable, possibly due to the narrow range of values for these measures.
      Except for approximately 10% fewer saccades during pursuit and fixation in the
      morning, there were no consistent diurnal differences. These findings suggest
      that, in a small sample of subjects, most measures of oculomotor function are
      stable across time and may reflect underlying neurophysiologic traits.

PMID- 7578656
TI  - All-night EEG spectral analysis as a tool for the prediction of clinical response
      to antidepressant treatment.
AB  - Earlier investigations have suggested that variables derived from quantified
      electroencephalographic (EEG) sleep analysis might predict good clinical response
      in an early phase of antidepressant treatment. In this report we evaluate the
      predictive value of all-night sleep EEG spectral analysis during the washout
      period before treatment. We compared the spectral EEG sleep profiles of major
      depressed inpatients divided into two groups according to an improvement > or =
      50% on the Hamilton Rating Scale for Depression. Findings in this population
      demonstrate the presence of specific characteristics of the responder group
      compared with the nonresponder group. Delta band relative power was increased in
      the former group, while theta, alpha, and beta relative power were decreased. All
      the bands showed decrease in absolute power in the responder group. These results
      can be interpreted as enhanced sleep intensity in the responder group. All-night
      sleep EEG spectral variables are valid baseline markers of the functional
      differences between treatment responders and nonresponders and thus might permit
      prediction of clinical outcome.

PMID- 7578653
TI  - Effects of tryptophan depletion on responses to yohimbine in healthy human
      subjects.
AB  - There is considerable evidence that both the norepinephrine (NE) and serotonin (5
      HT) systems are involved in the regulation of human anxiety and fear responses.
      To assess the modulating effects of central 5-HT levels on NE function, 11
      healthy human subjects were studied with placebo-controlled challenge tests
      involving tryptophan depletion followed by administration of the alpha-2
      adrenergic antagonist yohimbine 0.4 mg/kg IV. Five of the 11 subjects reported a
      marked increase in feelings of nervousness (> or = 25 mm on a 100 mm analog
      scale) following the combination test, while 1/11 had this response to yohimbine
      alone. No subjects had an increase in nervousness during other control tests. The
      increase in nervousness after the tryptophan depletion-yohimbine test was
      statistically significant for the whole group, but there were no other unique
      changes in behavioral, physiologic or biochemical (MHPG, cortisol) variables with
      this test. These data are discussed in terms of possible functional interactions
      between the 5-HT and NE neurotransmitter systems.

PMID- 7578657
TI  - m-Chlorophenylpiperazine in patients with obsessive-compulsive disorder: absence
      of symptom exacerbation.
AB  - Oral administration of the serotonin mixed agonist-antagonist meta
      chlorophenylpiperazine (mCPP) at 0.5 mg/kg has been reported to exacerbate
      symptoms of obsessive-compulsive disorder (OCD). In an attempt to replicate these
      findings, double-blind behavioral and biochemical measures were obtained in 12
      drug-free patients (9 men, 3 women) with OCD who received either oral mCPP (0.5
      mg/kg), intravenous (IV) mCPP (0.1 mg/kg over 20 min), or placebo in random order
      on 3 separate test days. Neither oral nor IV mCPP had significant effects on the
      severity of OCD symptoms. The magnitude of the mCPP-induced plasma prolactin
      response and plasma mCPP levels were similar to those values obtained in other
      published studies in which mCPP exacerbated OCD symptoms. In contrast, both oral
      and IV mCPP were associated with significant increases in ratings of anxiety.
      These findings suggest that mCPP, whether administered by an oral or intravenous
      route (as a slow infusion), may not be a reliable probe for investigating
      obsessive-compulsive symptoms. It is possible, however, that more reproducible
      behavioral findings might be obtained by identifying susceptible subgroups of OCD
      or by including a behavioral exposure condition.

PMID- 7578658
TI  - Auditory event-related brain potentials in autistic children and three different
      control groups.
AB  - ERPs to auditory stimuli, generated during an oddball task, were obtained in a
      group of autistic children and three control groups (normal, ADDH, and dyslectic
      children, respectively). The task included the presentation of standards,
      deviants, and novels and had a (between-group) passive vs. active (counting)
      condition. It was examined whether 1) it was possible to replicate several
      earlier findings, 2) autistics manifest an abnormal lateralization pattern of
      ERPs, 3) autistics have an abnormal mismatch negativity (MMN), and 4) differences
      between autistics and normals are really specific to the autistic group. The only
      finding that could be replicated was that autistics have a smaller A/Pcz/300.
      There was no evidence for abnormal lateralization or abnormal MMN; however, there
      was an unexpected effect of the task manipulation on the amplitude of the P3: in
      autistics, the occipital P3 to deviant stimuli was significantly larger in the
      active than in the passive condition, a finding, like the replication of the
      smaller A/Pcz/300, specific to the autistic group. It was suggested that the
      auditory occipital task effect is related to understimulation of the occipital
      lobe by visual stimuli in autistic children.

PMID- 7578659
TI  - Plasma neurotransmitters, blood pressure, and heart rate during supine-resting,
      orthostasis, and moderate exercise conditions in major depressed patients.
AB  - Major depressed patients showed greater heart rate, noradrenaline, and free
      serotonin values than normal. Conversely, platelet-serotonin values in major
      depressed patients were significantly lower than normal. Patients registered the
      normal differential blood pressure reduction during orthostasis. They also
      revealed progressive and significantly higher heart rate rises during orthostasis
      and exercise periods, when compared to normals. Whereas noradrenaline showed
      maximal rises during the two last periods, adrenaline only showed small but
      significant increase during exercise. The analysis of correlations, together with
      the above data, suggests that major depressed patients register maximal neural
      sympathetic activity as well as adrenal glands sympathetic hypoactivity. In
      addition, these patients show hyperparasympathetic activity, as reflected by the
      free-serotonin profile. Finally, the fact that both the Hamilton Depression
      Rating Scale and the self-rating Beck Depression Inventory correlated positively
      with noradrenaline/adrenaline ratio and free-serotonin values strongly suggests
      that both neural sympathetic and cholinergic mechanisms are involved in major
      depression.

PMID- 7578660
TI  - Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD.
AB  - Prominent heightened arousal symptoms and clinical/laboratory findings implicate
      the central noradrenergic system in posttraumatic stress disorder (PTSD).
      Heightened arousal frequently manifests in relation to sleep in PTSD. Central
      noradrenergic systems have a role in regulating arousal levels during sleep. We
      therefore evaluated noradrenergic production via urinary excretion in relation to
      sleep/wake activity in PTSD patients and controls. Twenty patients--all Vietnam
      veterans diagnosed with combat-related PTSD--and eight non-ill, non-combat
      exposed controls had overnight sleep studies under medication and substance-free
      conditions. In association with sleep recording, subjects saved their urine for
      24 hours in three 8-hour collections in order to obtain "daytime" (8:00 AM to
      4:00 PM, 4:00 PM to MN) and "nocturnal" (MN to 8:00 AM) catecholamine measures.
      PTSD patients had decreased sleep efficiency relative to controls and increased
      REM density; 24-hour norepinephrine and MHPG (the more centrally derived
      metabolite) did not differ between patients and controls. "Nocturnal" excretion
      of MHPG minus the average of the two "daytime" values was negative in the
      controls, slightly positive in the patients, and differed significantly between
      the two groups. "Nocturnal minus daytime" MHPG also correlated negatively with
      total sleep time in the PTSD patients (R = -.45, p < .05). Our data support a
      relationship of nondiminished central noradrenergic activity at night, and sleep
      disturbance, in chronic, combat-related PTSD.

PMID- 7578663
TI  - Recurrent absence status epilepticus and hyponatremia in a patient with
      polydipsia.

PMID- 7578661
TI  - Reduced echogenicity of brainstem raphe specific to unipolar depression: a
      transcranial color-coded real-time sonography study.
AB  - Echogenicity of the brainstem raphe was assessed in patients with major
      depression, bipolar affective disorders, and schizophrenia and compared with
      healthy adults employing transcranial color-coded real-time sonography. Forty
      probands were enrolled in each group. A highly significant reduction in raphe
      echogenicity was detected only in patients suffering from major depression.
      Echogenicity of the raphe was independent of age or sex and did not correlate
      with severity of the depressive syndrome or patient state. These findings are
      suggestive of structural desintegration of the brainstem raphe in unipolar
      depression, an anatomical region assumed to be a biological focus in the
      pathogenesis of depressive syndromes.

PMID- 7578664
TI  - Tricyclic-induced musical hallucinations and states of relative sensory
      deprivation.

PMID- 7578662
TI  - Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and clinical symptoms in
      Alzheimer's disease.
AB  - Postmortem findings point to significant abnormalities in central noradrenergic
      function in Alzheimer's disease (AD) which may be associated with changes in
      peripheral markers. In this study, the relationship between the peripheral
      noradrenergic marker, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), and clinical
      symptoms was examined in 23 patients with probable AD. Basal MHPG levels
      correlated significantly with increased cognitive impairment (r = .58, p = .005),
      controlling for age, age at onset, gender, and time interval between plasma MHPG
      determination and cognitive testing. These results suggest that plasma MHPG
      increases as cognitive function in AD deteriorates, further supporting
      preliminary evidence for increases in noradrenergic indices in association with
      disease severity in AD.

PMID- 7578665
TI  - Neuroleptic-induced emesis: a new indication for clozapine?

PMID- 7578667
TI  - Negative correlation between alpha-1-acid-glycoprotein plasma level and response
      to haloperidol in the acute treatment of schizophrenia.

PMID- 7578669
TI  - Progesterone concentrations in serum, follicular fluid, and oviductal fluid of
      the golden hamster during the periovulatory period.
AB  - In vitro, progesterone induces capacitation, hyperactivated motility, and
      acrosome reactions in sperm, possibly acting through a non-genomic plasma
      membrane receptor, but neither progesterone functions nor concentration within
      the mammalian oviduct during the periovulatory period is well characterized. The
      objectives of this study were to determine the physiological concentrations of
      progesterone in serum, follicular fluid, and oviductal fluid of golden hamsters
      during the period of the reproductive cycle in which capacitation and
      fertilization occur. Fluids were collected from different groups of animals for
      each of four time points: the normal time for mating (5-6 h post-LH surge [post
      LH]), early in capacitation (8-9 h post-LH), immediately preovulation (11-12 h
      post-LH), and after ovulation near the beginning of fertilization (14-15 h post
      LH). Oviductal fluid was collected by 1-h cannulation followed by cardiac
      puncture for serum collection and follicle aspiration for follicular fluid.
      Within each time period, the three types of fluid differed significantly in
      progesterone concentration. Over time, concentrations of progesterone did not
      change in either serum (range: 5.64-12.85 ng/ml) or follicular fluid (range: 4.2
      7.4 micrograms/ml), but the concentration of progesterone in oviductal fluid
      decreased from 175.06 ng/ml at the first period to 44.01 ng/ml at the fourth (p <
      0.05), while the volume of oviductal secretions collected by the same sampling
      procedure increased from 1.6 to 2.9 microliters (p < 0.05). With this information
      concerning in vivo concentrations of progesterone during capacitation and
      fertilization, the physiological role of progesterone in sperm-egg interactions
      can be addressed.

PMID- 7578668
TI  - Growth hormone response to clonidine in nondepressed patients with a history of
      suicide attempts.

PMID- 7578670
TI  - Effects of progesterone on in vitro sperm capacitation and egg penetration in the
      golden hamster.
AB  - Progesterone (P) is postulated to have a physiological role in vivo during sperm
      capacitation and/or during sperm-egg interaction as a cofactor for induction of
      the acrosome reaction. Effects on in vitro fertilization were tested by adding P
      (0.01-2 micrograms/ml) to sperm during capacitation (4-6 h) or after capacitation
      during sperm-egg interaction for 1 h. Additionally, to test for acceleration of
      the onset of capacitation by P, eggs were inseminated with sperm that were
      incubated with P for 3.5 and 5 h. Neither the solvent dimethyl sulfoxide nor P
      affected the motility or vigor of treated sperm. The effects of P on egg
      penetration were dependent on the dose, the temporal sequence of its addition to
      sperm (i.e., before or after capacitation), and the duration of sperm exposure.
      Capacitation of sperm with 20 ng/ml P for 5 h, but not 3.5 h, increased the
      percentage of eggs penetrated by sperm over controls (52.65 +/- 4.01% vs. 39.30
      +/- 5.18%, p < 0.05). But P (0.01-2 micrograms/ml), either added after
      capacitation (4.5 h) during sperm-egg coincubation (1 h) only, or present (1
      micrograms/ml) throughout capacitation (4-6 h) and sperm-egg coincubation (1 h),
      did not increase egg penetration over control levels. In conclusion, the best
      results occurred with a protocol that mimicked in vivo conditions of capacitation
      time (5 h) and preovulatory oviductal levels of P (20 ng/ml).

PMID- 7578666
TI  - Clozapine in tardive Tourette syndrome.

PMID- 7578672
TI  - Haploid gene expression: temporal onset and storage patterns of 13 novel
      transcripts during rat and mouse spermiogenesis.
AB  - The temporal and spatial expression of thirteen novel spermatid-specific genes
      corresponding to cDNA clones isolated from an adult mouse testis library was
      analyzed. Northern analysis of RNA from seminiferous tubules at defined stages of
      the rat and mouse seminiferous epithelial cycle and in situ hybridization of
      testis sections revealed that these mRNAs were expressed in a stage-specific
      manner. The expression of all mRNAs was first detected in early round spermatids,
      and it increased to abundance during stages VII-VIII of the epithelial cycle.
      Twelve out of thirteen mRNAs were found not only in round spermatids but also in
      transcriptionally inactive elongated spermatids, suggesting that they are stored
      and regulated at the translational level. The variation in the length of the
      poly(A) tail was detected for four of the transcripts, represented by cDNA clones
      MTEST70, MTEST627, MTEST641, and MTEST643 at defined stages of the cycle.
      Similarity in the stage-specific expression pattern displayed by this group of
      haploid-specific genes strongly suggests the presence of common regulatory
      mechanisms that act during spermiogenesis, and these genes also provide a means
      for further studies of these mechanisms.

PMID- 7578671
TI  - Polymeric immunoglobin (Ig) receptor production and IgA transcytosis in polarized
      primary cultures of mature rat uterine epithelial cells.
AB  - These studies were conducted to more fully understand the role of uterine
      epithelial cells (UEC) in immunoglobin (Ig)A movement from tissue into secretions
      in the female reproductive tract. Indirect immunofluorescence and image analysis
      showed that the polymeric Ig receptor (pIgR), which is responsible for
      transporting polymeric IgA (pIgA) across epithelial cells, was expressed in
      uterine tissues from rats throughout the estrous cycle. UEC pIgR levels were
      higher at estrus than at either proestrus or diestrus. When UEC were isolated
      from the uteri of adult rats and grown on cell culture inserts, cells grew to
      confluence, formed tight junctions, and released secretory component (SC), the
      external domain of the pIgR, into the apical medium. Irrespective of whether UEC
      were isolated from the uteri of rats at the diestrous, proestrous, or estrous
      stages of the reproductive cycle, cells produced SC, indicating that they are
      capable of IgA transport. 125I-IgA was preferentially transcytosed from the
      basolateral to the apical surface, demonstrating that dimeric IgA (dIgA) could be
      transported by UEC in culture. In contrast, the fluid phase marker [3H]inulin
      moved at a comparable rate in both directions across the cell monolayer. 125I-IgA
      transport through UEC was saturable and specific for pIgA in that unlabeled pIgA,
      but not IgG, inhibited 125I-dIgA transcytosis from the basolateral to the apical
      surface. Immunoprecipitation of 125I-IgA in the apical chamber with rabbit anti
      SC antibody indicated that after transepithelial movement, IgA was bound to SC.
      Northern blot analysis of RNA extracted from UEC demonstrated that cells
      continued to synthesize pIgR mRNA in culture. Our results suggest that in the
      uterus, epithelial cells play a key regulatory role in the control of IgA
      transcytosis from tissue into secretions.

PMID- 7578673
TI  - Development of immortalized endometrial epithelial and stromal cell lines from
      the mink (Mustela vison) uterus and their effects on the survival in vitro of
      mink blastocysts in obligate diapause.
AB  - Mink endometrial cell lines were established by stable transfection of a plasmid
      vector encoding the SV40 large T antigen driven by the human beta-actin promoter.
      A second plasmid vector, pSV2neo, was employed for selection of transfected
      cells. Specificity and homogeneity of consequent cell lines were evaluated by
      immunocytochemistry employing antibodies against cytokeratin, desmin, and
      vimentin. Cytokeratin was found exclusively in epithelial cells, whereas vimentin
      appeared primarily in stromal cells. Neither cell line showed detectable desmin
      activity. These cell lines along with Buffalo rat liver (BRL) cells were employed
      in coculture with mink embryos in obligate diapause. Mink stromal and BRL cell
      lines were most effective in enhancing embryo survival in vitro. The percentages
      of cocultured embryos that survived for 72 h or more were 65% with epithelial
      cells, 75% with stromal cells, 68% with the combination of stromal and epithelial
      cells, and 93% with BRL cells. Only 23% of the embryos cultured without cells
      survived beyond 48 h. Embryo growth was also observed; some embryos in coculture
      showed trophoblastic outgrowth and adhesion to the cell surfaces. These results
      demonstrate that mink embryos in obligate delay can survive and develop in
      culture and that coculture with uterine or BRL cells increases the length and
      frequency of survival.

PMID- 7578674
TI  - Parturition in the rabbit is compromised by daytime nursing: the role of
      oxytocin.
AB  - Rabbits nurse briefly only once each night and are frequently both pregnant and
      lactating. To investigate the influence of the daily timing of nursing on
      parturition, does (n = 10 per group) were remated after giving birth and were
      allowed to nurse under one of three schedules: group 1 every 24 h in the light,
      group 2 every 24 h in the dark, and group 3 at any time. Whereas does from groups
      2 and 3 nursed and gave birth normally, does of group 1, forced to nurse out of
      phase with the normal schedule, showed disturbed nursing behavior and prolonged
      gestation followed by many stillbirths. In a second experiment, pregnant does (n
      = 10 per group) were treated daily either with oxytocin (OT) in the light (group
      4), with OT in the dark (group 5), or with progesterone (P; group 6) or saline
      (group 7) in the light. All does gave birth normally except those of group 4,
      which responded similarly to group 1 does. These findings demonstrate that in the
      rabbit, parturition may be seriously compromised if does nurse out of phase with
      the normal schedule and suggest that a shift in the daily timing of OT release
      may underlie this.

PMID- 7578676
TI  - Expression of genes encoding antioxidant enzymes in preimplantation mouse and cow
      embryos and primary bovine oviduct cultures employed for embryo coculture.
AB  - Preimplantation embryos from a variety of mammalian species contrast markedly in
      their response to culture in vitro. Murine preimplantation embryos display a
      wider tolerance than other mammalian species to culture environments, and this
      has contributed to the development of several effective defined culture media.
      Embryo coculture on somatic cells remains the most effective method of supporting
      reasonable rates of bovine preimplantation development in vitro. The patterns of
      gene expression for several antioxidant enzymes during preimplantation murine and
      bovine development were examined by use of the reverse transcription-polymerase
      chain reaction technique to determine whether the differential developmental
      capacity of mammalian preimplantation embryos in culture may reflect variations
      in the patterns of expression for a series of antioxidant enzymes. Transcripts
      for catalase, CuZn-containing superoxide dismutase (CuZn-SOD), Mn-SOD,
      glutathione peroxidase (GPX), and glutamylcysteine synthetase (GCS) were detected
      in mouse embryos at all stages of development regardless of in vivo or in vitro
      development. Preimplantation cow embryos produced by in vitro procedures
      expressed mRNAs for catalase, CuZn-SOD and GPX, whereas transcripts for Mn-SOD
      were not detected at any stage. GCS transcripts, although present in stages up to
      the morula, were not detected in cow blastocysts. Analysis of antioxidant gene
      expression in both bovine primary oviductal cell monolayer cultures and
      nonattached, ciliated oviductal cell vesicle cultures revealed a constitutive
      pattern of expression of all five enzymes for the 8-day culture interval. These
      experiments suggest that differences in gene expression may contribute to the
      variation in the ability of embryos to develop in vitro with respect to levels of
      oxygen and dependence on coculture.

PMID- 7578677
TI  - Gonadotropin-releasing hormone increases cleavage rates of bovine oocytes
      fertilized in vitro.
AB  - Because a direct effect of GnRH on spermatozoa has been implied in clinical
      studies with subfertile bulls and stallions, we added GnRH to in vitro
      fertilization media to study effects on cleavage rates of bovine oocytes obtained
      from slaughterhouse ovaries. Cleavage rates were higher (p < 0.01) in media
      containing 0.8 microgram/ml GnRH (68%) than in controls (59%) and were consistent
      across three bulls. In a second experiment two GnRH agonists also increased
      cleavage rates. A dose response for GnRH was demonstrated in a third experiment
      with a low-fertility bull (p < 0.09): cleavage rates were 37, 36, 43, 48, and 47%
      for 0, 0.16, 0.8, 4, and 20 micrograms/ml GnRH, respectively. A GnRH antagonist
      was also shown to abolish the enhancing effect of GnRH on cleavage rates. No
      significant (p > 0.10) effect on percentage blastocysts per cleaved ovum was
      detected in any experiment. No specific binding of a GnRH analog to sperm was
      detected in radioreceptor assays. However, mRNA for the GnRH receptor was
      detected in matured cumulus-oocyte complexes by means of reverse transcription
      polymerase chain reaction and was verified by Southern hybridization with cDNA
      for the ovine GnRH receptor. In summary, GnRH and GnRH agonists enhance bovine in
      vitro fertilization, and detection of mRNA for the GnRH receptor in cumulus
      oocyte complexes is suggestive that GnRH may act through its receptor.

PMID- 7578675
TI  - Evidence for follicle-stimulating hormone mediation in the hemiorchidectomy
      induced compensatory increase in the function of the remaining testis of the
      adult male bonnet monkey (Macaca radiata).
AB  - Hemiorchidectomy (HO) in the adult male bonnet monkey results in a selective
      increase in circulating concentrations of FSH and testosterone, and this is
      accompanied by compensatory increase in sperm production by the remaining testis.
      We investigated the possible role of increased FSH concentration that occurs
      after HO in the compensatory increase in the activity of the remaining testis. Of
      eight adult male bonnet monkeys that underwent HO, four received i.v. injections
      every other day for 30 days of a well-characterized ovine FSH antiserum (a/s)
      that cross-reacts with monkey FSH. The remaining four males received normal
      monkey serum (NMS) as control treatment in a protocol similar to that employed
      for a/s-treated males. Blood samples were collected between 2100 and 2200 h
      before and 1/2, 1, 3, 5, 7, 14, 22, and 29 days after HO. Testicular weight,
      number of 3 beta-hydroxy steroid dehydrogenase-positive (3 beta-HSD+) cells, and
      DNA flow cytometric analysis of germ cell populations were obtained for testes
      collected before and at the termination of NMS or a/s treatment. In NMS-treated
      males, circulating serum FSH concentrations progressively increased to reach a
      maximal level by Day 7 after HO (1.95 +/- 0.3 vs. 5.6 +/- 0.7 ng/ml on Days -1
      and 7, respectively). Within 30 min of a/s injection, FSH antibodies were
      detected in circulation, and the antibody level was maintained at a constant
      level between Day 7 and end of treatment (exhibiting 50-60% binding to 125I
      hFSH).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578678
TI  - Influence of tumor necrosis factor alpha on intracellular Ca2+ in hen granulosa
      cells in vitro during follicular development.
AB  - In the present study, we have determined the influence of tumor necrosis factor
      alpha (TNF alpha) on both basal and carbamylcholine chloride (Cch)-induced
      [Ca2+]i in granulosa cells from the largest (F1) and smallest (F5,6) preovulatory
      follicles. TNF alpha (10 ng/ml) induced a small (51-63 nM) and delayed
      (approximately 1 min) transient increase in [Ca2+]i. The percentage of cells that
      responded to the cytokine was greater in F5,6 granulosa cells (48%; n = 48) than
      F1 granulosa cells (24%; n = 41). These responses were completely abolished in
      Ca(2+)-free media containing 5 mM EGTA and 2.5 mM Mg2+ or 1 mM Mn2+. Cch induced
      large increases (> 250 nM) in [Ca2+]i via mobilization of Ca2+ from intracellular
      stores in approximately 50% of Cch-responsive F1 granulosa cells but only about
      15% of Cch-responsive F5,6 cells. Pretreatment with TNF alpha (4-5 min) increased
      the magnitude of the Cch response in both F1 and F5,6 granulosa cells previously
      incapable of producing large Cch-induced changes in [Ca2+]i. In F1 cells, the
      effects of TNF alpha on Cch-induced [Ca2+]i were far more extensive, such that
      the Cch response in the presence of TNF alpha was indistinguishable from the fast
      Cch-induced Ca2+ transient reported previously. Furthermore, the TNF alpha effect
      was reversible, as subsequent challenge with Cch in the absence of TNF alpha
      failed to produce the large Ca(2+)-transients observed earlier with the cytokine
      present. In conclusion, TNF alpha induces transient increases in [Ca2+]i by
      transmembrane Ca2+ flux, which are suppressed during cytodifferentiation. In
      addition, TNF alpha appeared to enhance Cch-induced mobilization of Ca2+ from
      intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578679
TI  - Oxytocin and oxytocin receptor gene expression in the reproductive tract of the
      pregnant cow: rescue of luteal oxytocin production at term.
AB  - The peptide hormone oxytocin is produced both in the hypothalamus and in certain
      peripheral organs. The extent of extra-hypothalamic hormone synthesis in the
      pregnant cow has not previously been examined. In this study we have analyzed
      different tissues from the pregnant bovine reproductive tract and corpus luteum
      for the presence of mRNA encoding the oxytocin peptide as well as the oxytocin
      receptor. In uterine tissues oxytocin mRNA could only be detected sporadically
      with the help of a reverse transcription-polymerase chain reaction method,
      implying only very low levels of expression. The caruncles showed a consistently
      low level of oxytocin gene expression, which appeared up-regulated at term.
      However, in the corpus luteum there was a significant level of oxytocin gene
      expression at term, particularly following the onset of labor. The transcript
      levels were sufficiently high to be measurable by both RNase protection assay and
      by Northern hybridization; these levels imply a rescue of the oxytocin gene
      expression seen in the corpora lutea of cyclic and early pregnant cows. At the
      peptide level this expression was confirmed by immunohistochemistry. A sensitive
      RNase protection assay was developed to detect transcripts encoding the oxytocin
      receptor. Transcripts were detected in most uterine tissues, including the
      caruncles, with highest levels in the endometrium and myometrium at term. No
      transcripts could be detected in the corpus luteum at any stage of pregnancy, nor
      in the amnion. The results suggest the possibility of local, paracrine effects of
      oxytocin within the uterus of the pregnant cow. The rescue of luteal oxytocin at
      term could act to supplement the circulating hormone of pituitary origin.

PMID- 7578680
TI  - Regulated synthesis and localization of DNA methyltransferase during
      spermatogenesis.
AB  - Differences in the methylation patterns of male and female gamete DNA are likely
      to be involved in genomic imprinting. However, little is known of the mechanisms
      that regulate de novo methylation and demethylation during gametogenesis. We
      report here that the well-characterized M(r) 190,000 form of DNA
      methyltransferase (the only known form) is present in isolated mitotic, meiotic,
      and postmeiotic male germ cells, with the exception of meiotic pachytene
      spermatocytes, where the protein is undetectable by immunoblot analysis and a
      novel 6.2-kb DNA methyltransferase transcript is present. Whereas replication and
      methylation are coupled in somatic cells, the presence of DNA methyltransferase
      in postreplicative male germ cells is consistent with previously observed de novo
      methylation events in these cells. Immunofluorescence experiments revealed that
      DNA methyltransferase is localized to the nuclei of male germ cells, with a
      subset of spermatogonia and postreplicative leptotene/zygotene spermatocytes
      displaying prominent nuclear foci that are strongly enriched in DNA
      methyltransferase. The data suggest that down-regulation of DNA methyltransferase
      expression during the pachytene stage of meiosis utilizes an mechanism that is
      associated with the production of a larger mRNA, and that de novo methylation in
      leptotene/zygotene spermatocytes may take place in spatially restricted nuclear
      domains that are enriched in DNA methyltransferase.

PMID- 7578681
TI  - Characteristics of A spermatogonia and preleptotene spermatocytes in the vitamin
      A-deficient rat testis.
AB  - The proliferative activity and other characteristics of germ cells in the vitamin
      A-deficient (VAD) rat testis were investigated. In the VAD testis, A
      spermatogonia and preleptotene spermatocytes were found. The A spermatogonia in
      the VAD testis showed a bromodeoxyuridine (BrdU) labeling index of 6.6 +/- 1.1%
      and a mitotic index of 2.8 +/- 0.5%. After continuous labeling with BrdU for up
      to four days, the ultimate labeling index of A spermatogonia was 11.6 +/- 2.5%,
      which is less than expected. It is concluded that in the VAD rat testis, many of
      the proliferating A spermatogonia degenerate. During the first 18 h after
      administration of vitamin A, no increase was observed in either the labeling
      index or the mitotic index of the A spermatogonia. However, after 24 h the first
      wave of A spermatogonia in S phase was found, and the first wave in mitosis was
      found after 48 h. Furthermore, in the VAD testis the DNA content of most of the A
      spermatogonia was similar to that of Sertoli cells, i.e., 2n. It is concluded
      that in the VAD situation, nearly all A spermatogonia are arrested before the S
      phase of the A1 spermatogonia. The hypothesis is put forward that in the VAD
      testis, the remaining A spermatogonia are the undifferentiated spermatogonia that
      are unable to differentiate into A1 spermatogonia. The preleptotene spermatocytes
      in the VAD testis showed a BrdU labeling index of 20.3 +/- 3.5%, while the DNA
      content of most of these cells was between 3n and 4n.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7578682
TI  - Sequence and localization of the mouse sperm autoantigenic protein, Sp17.
AB  - The present study characterizes the sperm protein Sp17 in the mouse. Sp17 is a
      mammalian testis- and sperm-specific protein that has been isolated, sequenced,
      and characterized from rabbit testis and spermatozoa. In this study, a rabbit
      Sp17 cDNA probe representing the entire protein coding region was used to screen
      a mouse testis cDNA library to obtain the mouse Sp17 sequence. The mouse mRNa for
      Sp17 encodes a 149-amino acid protein with a predicted molecular weight of
      17,296. The mouse Sp17 (MSp17) cDNA sequence is 82% identical to the rabbit Sp17
      cDNA sequence while the MSp17 protein sequence is 74% identical to the rabbit
      protein sequence. The presence of native Sp17 in mouse spermatozoa and testis was
      demonstrated by Western blot analysis, immunoprecipitation, and
      immunolocalization. After SDS-PAGE, the native Sp17 has an apparent molecular
      mass of 24 kDa. The sequence of the native Sp17 was confirmed by Western blots of
      mouse testis and spermatozoa probed with two anti-peptide antibodies--one, anti
      G22C, made against amino acids 61-82 in the rabbit sequence (61-83 in the mouse),
      and a second, anti-K18C, made against amino acids 120-136 in the C-terminal
      region in the human sequence (118-134 in the mouse sequence). In the absence of
      proteolytic inhibitors, part of the C-terminal of native MSp17 is cleaved, giving
      rise to an 18-kDa band. Sp17 is present in spermatocytes and spermatids in the
      testis. In spermatozoa, Sp17 is not available to bind antibody on the surface of
      live, acrosome-intact spermatozoa, but it is present on the equatorial surface of
      live, acrosome-reacted spermatozoa. In fixed spermatozoa, staining is observed
      along the length of the principal piece, weakly along the midpiece, and over the
      acrosomal region of the head. When the acrosome reaction begins, acrosomal
      staining is seen throughout the equatorial region of the acrosome. Using mimotope
      analysis, this study has also demonstrated that native Sp17 is a sperm
      autoantigen and that recombinant mouse Sp17 is immunogenic in males with a highly
      restricted linear epitope.

PMID- 7578683
TI  - Decreased expression of functional human chorionic gonadotropin/luteinizing
      hormone receptor gene in human uterine leiomyomas.
AB  - Human myometrium contains functional hCG/LH receptors. The purpose of this study
      was to determine whether or not leiomyomas that arise from myometrium also
      contain these receptors. Northern blotting demonstrated that leiomyomas and
      normal adjacent myometria contained hCG/LH receptor mRNA transcripts. Western
      immunoblotting showed that leiomyomas and corresponding normal myometria also
      contained 60- and 50-kDa receptor proteins. Ligand blotting revealed that only
      the 50-kDa receptor protein in leiomyomas and corresponding normal myometria
      could bind 125I-hCG and that this binding inhibited by excess unlabeled hCG. In
      situ hybridization and immunocytochemistry revealed that smooth muscle cells in
      leiomyomas and corresponding normal myometria contained the hCG/LH receptor mRNA
      transcripts and receptor proteins. The receptor levels were lower in leiomyomas
      than in corresponding normal myometria. However, the receptors were functional,
      as treatment with hCG resulted in a decrease of connexin-43 protein levels in
      leiomyomas as in normal myometria. In summary, human uterine leiomyomas express a
      functional hCG/LH receptor gene at a reduced level compared with that for normal
      corresponding myometria. This finding could be relevant to an understanding of
      the growth control mechanisms in leiomyomas and the manner in which medical
      therapy for leiomyomas might work.

PMID- 7578684
TI  - Smooth muscle myosin II and alpha smooth muscle actin expression in the baboon
      (Papio anubis) uterus is associated with glandular secretory activity and stromal
      cell transformation.
AB  - The objective of this study was to investigate the localization and hormonal
      regulation of smooth muscle myosin II (SMM II) and alpha smooth muscle actin
      (alpha SMA) in the baboon uterus, since cytoskeletal proteins are involved in
      secretory function and morphological transformation. Uterine tissue was obtained
      from baboons 1) during the menstrual cycle, 2) following steroid treatment of
      ovariectomized baboons, 3) during pregnancy (Days 14-60 postovulation [PO]), and
      4) during simulated pregnancy (Days 18-32 PO). Tissues were processed for
      immunocytochemical localization of SMM II or alpha SMA with specific polyclonal
      or monoclonal antibodies, respectively. SMM II stained all smooth muscle cells of
      blood vessels and myometrium regardless of treatment. Glandular epithelial
      staining was present only in endometrium obtained during the luteal phase or
      following estrogen and progesterone treatment. Staining intensity was greater in
      the basalis than in the functionalis. The number of glands staining positive for
      SMM II on Days 18-32 of pregnancy and simulated pregnancy was variable. Glandular
      stain was absent after Day 32 PO. These immunocytochemical data were confirmed by
      immunoblot analysis of glandular cytosolic extracts. Stromal staining for SMM II
      was present under the luminal epithelium during simulated pregnancy (Days 18-32),
      on Day 25 of steroid treatment in the simulated-pregnant controls, and in
      nonimplantation sites during pregnancy. In contrast, alpha SMA staining was low
      or absent in all uterine cell types in ovariectomized baboons. Under estrogen
      dominated conditions (follicular phase and estrogen treatment), alpha SMA
      staining was present in smooth muscle cells, and this staining persisted
      throughout the remaining treatment periods. Glandular epithelial staining for
      alpha SMA was absent in all treatment groups. However, alpha SMA staining in
      stromal fibroblasts underneath the luminal epithelium was evident as early as Day
      14 of pregnancy and Day 18 of simulated pregnancy. The number of stromal
      fibroblasts that stained positive increased in the surface region of the
      functionalis between Days 18 and 32 PO, and the staining extended throughout the
      upper functionalis region. There was a decrease in the number of positively
      stained stromal fibroblasts, particularly at the implantation site, between Days
      32 and 40 of pregnancy. By Days 50-60 of pregnancy, this staining was almost
      absent. The induction of alpha SMA in stromal fibroblasts in the functionalis
      region in pregnant baboons was confirmed by immunoblot analysis of stromal cell
      cytosol extracts. We conclude that the progesterone-induced glandular expression
      of SMM II may be involved in uterine secretory function and that alpha SMA
      expression in stromal fibroblasts during pregnancy and after long-term steroid
      treatment is associated with the decidualization process.

PMID- 7578685
TI  - Autologous regulation of androgen receptor messenger ribonucleic acid in the
      separate lobes of the rat prostate gland.
AB  - Differential autoregulation of androgen receptors (AR) has been previously
      described for the separate lobes of the rat prostate gland. While AR are up
      regulated by testosterone in the ventral, dorsal, and LP1 lateral lobes, the
      epithelial cells of the LP2 lateral ducts show continued expression of the AR
      protein following androgen withdrawal. To determine the mechanism of this
      differential autologous regulation, the present study examined the autoregulation
      of AR mRNA in the separate regions of the rat prostate gland. Northern blot
      analysis revealed that AR mRNA levels are down-regulated by androgens in all
      prostate lobes, since their levels increase following castration and decrease
      upon testosterone replacement. In situ hybridization confirmed that the increase
      in AR mRNA levels immediately following androgen withdrawal is due to increased
      transcripts per cell. When normalized to DNA content, the AR mRNA elevation upon
      androgen withdrawal was transient, and the value returned to control levels in
      the ventral and dorsal lobes within three days, while the elevation of AR message
      in the lateral lobe was prolonged. Quantitative reverse transcriptase-polymerase
      chain reaction studies revealed that elevated AR mRNA levels in the prolonged
      absence of androgens were confined to the LP2 ducts of the lateral lobe. Nuclear
      run-on experiments showed no alteration in AR gene transcription two days after
      castration in the ventral, dorsal, or LP1 lateral lobes when compared to the
      values in intact rats, indicating that posttranscriptional mechanisms are
      involved in AR mRNA autoregulation. In contrast, the AR gene transcription rate
      doubled in the lateral LP2 ducts. The elevated AR mRNA levels in the LP2 ducts
      due to increased AR gene transcription following castration may, in part, explain
      the continued expression of AR protein in that region in the absence of
      testosterone. However, the mechanism whereby AR translation becomes uncoupled
      from its AR mRNA levels in the ventral and dorsal lobes after hormone withdrawal
      remains unclear. In summary, the present data demonstrate that differences exist
      in AR mRNA regulation within the different regions of the rat prostate gland.
      These differences may begin to explain differential autoregulation of the AR
      protein in the separate prostate lobes.

PMID- 7578687
TI  - Estradiol-17 beta, insulin-like growth factor-I, and luteinizing hormone inhibit
      secretion of transforming growth factor beta by rat ovarian theca-interstitial
      cells.
AB  - Theca cells have been shown to secrete transforming growth factor beta (TGF
      beta), but little is known regarding the regulation of thecal TGF beta secretion.
      To investigate the regulation of thecal TGF beta secretion and activation, rat
      theca-interstitial cells (TIC) isolated by Percoll gradient centrifugation were
      cultured with LH (0.01-10 ng/ml), androstenedione, androsterone, testosterone, or
      5 alpha-dihydrotestosterone (DHT) (all 1 x 10(-9)-1 x 10(-5) M), estradiol (E2),
      estrone (both 1 x 10(-11)-1 x 10(-7) M), or IGF-I (30 ng/ml). Active TGF beta and
      total TGF beta in the conditioned medium were measured by bioassay. TIC
      spontaneously produced TGF beta, of which approximately 45% was in the active
      form. LH inhibited total TGF beta secretion (45% at 0.1 ng/ml of LH) and active
      TGF beta concentrations (40% at 0.3 ng/ml of LH). IGF-I inhibited active but not
      total TGF beta. Addition of LH did not cause any additional change in active or
      total TGF beta. Neither androstenedione, androsterone, testosterone, nor DHT had
      any effect on either active or total TGF beta secretion in the presence or
      absence of LH. In contrast, E2 inhibited both active (57%) and total (37%) TGF
      beta secretion. In the presence of LH, no additional effect of E2 was observed.
      ICI 182,780, a pure estrogen antagonist, reversed the E2 inhibition, suggesting
      that the E2 effect is mediated by estrogen receptors. We next investigated the
      role of E2 on TGF beta production by granulosa cells (GC).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7578686
TI  - Corticotropin-releasing hormone stimulates steroidogenesis in mouse Leydig cells.
AB  - The actions of corticotropin-releasing hormone (CRH) on steroidogenesis in
      enriched preparations of mouse and rat Leydig cells were investigated. Primary
      cultures of purified Leydig cells as well as a Leydig tumor cell line were used
      in these studies. CRH had a stimulatory effect on steroid production in both
      isolated preparations of mouse Leydig cells (80-90% Leydig cells) and MA-10 cells
      (a mouse Leydig tumor cell line). In primary cultures of mouse Leydig cells, CRH
      was effective over a range of 1 nM-100 nM, while MA-10 cells were responsive over
      a wider range (10 nM-100 microM). When a submaximal dosage of CRH was given
      together with a maximal dosage of hCG, steroid production was stimulated even
      more highly in MA-10 cells. However, when primary cultures of mouse Leydig cells
      were treated with CRH and hCG, no similar response was observed. In addition, a
      CRH antagonist, alpha-helical CRH9-41, reversed the CRH stimulatory effect on
      steroidogenesis in both mouse Leydig cells and MA-10 cells. The accumulation of
      intracellular cAMP after CRH treatment was dose-responsive to CRH in both cell
      types, a finding similar to the results described above for steroid production.
      CRH had no effect on steroidogenesis in rat Leydig cells (60-80% Leydig cells) in
      the present study. These results indicate that mouse Leydig cells respond to CRH
      through specific receptors with increased production of cAMP and steroids.

PMID- 7578688
TI  - Isolation and characterization of heparin-binding growth factors in human
      leiomyomas and normal myometrium.
AB  - Uterine leiomyomas (fibroids) are benign, smooth muscle cell (SMC) tumors of the
      myometrium containing abundant extracellular matrix (ECM). Heparin-binding growth
      factors present in leiomyoma and normal myometrial fresh tissue were isolated
      using heparin-affinity fast protein liquid chromatography. Purification of these
      growth factors was monitored by the stimulation of [3H]thymidine incorporation
      into BALBc-3T3 cells and myometrial SMC. Western blot analysis confirmed that two
      consistent peaks of growth factor activity (eluting at 0.5 M NaCl and 1.7 M NaCl)
      were platelet-derived growth factor (PDGF), 31 kDa, and basic fibroblast growth
      factor (bFGF), 18 kDa, respectively. Northern blot analysis of leiomyoma and
      myometrial tissue revealed three RNA transcripts (2.8, 2.3, and 1.9 kb) for PDGF
      A chain, one RNA transcript (4.0 kb) for PDGF-B chain, and two RNA transcripts
      (3.7 and 3.5 kb) for bFGF. RNase protection assay showed elevated expression of
      the bFGF mRNA transcript in leiomyomas in 3 out of 5 patients. Immunoperoxidase
      staining of paraffin-embedded tissue showed that PDGF was predominantly
      intracellular in both vascular and myometrial SMC. Basic FGF, by contrast, was
      found primarily bound to the ECM of myometrium and fibroids. Leiomyomas showed
      much stronger staining for bFGF due to the large areas of ECM in these tumors. A
      third mitogenic peak eluting at 1.1 M NaCl was also seen in both myometrial and
      leiomyoma tissue. This peak was not definitively identified by Western blotting.
      However, Northern analysis for heparin binding-epidermal growth factor (HBEGF),
      which also elutes at 1.1 M NaCl, detected one RNA transcript for HBEGF (2.5 kb)
      in normal myometrium but little or no expression in the corresponding leiomyoma
      tissue. Immunoperoxidase staining showed that HBEGF was a cell-membrane
      associated protein in both normal myometrial and leiomyoma SMC with more intense
      staining in normal myometrium. These results show that both leiomyomas and
      myometrium synthesize a number of heparin-binding growth factors. The enhanced
      growth of leiomyomas may be due, in part, to the presence of large quantities of
      bFGF that are stored in the ECM of these tumors. In addition, the level of HBEGF
      mRNA declines during the transformation of myometrial SMC into leiomyomas.

PMID- 7578690
TI  - Epithelial lining of the sheep ampulla oviduct undergoes pregnancy-associated
      morphological changes in secretory status and cell height.
AB  - The biosynthetic activity of the sheep ampulla oviduct changes during the first
      few days of pregnancy. An estrogen (E2)-dependent glycoprotein (M(r) 90,000
      92,000) is expressed, synthesized, and released when fertilization and embryo
      development occur in the oviduct. The objective of the present study was to
      determine whether the secretory epithelial lining of the ampulla, the cellular
      source of the E2-dependent protein, undergoes morphological alterations during
      early pregnancy is a contemporaneous manner. Ampulla oviducts obtained from
      ovariectomized (ovx), estrous (Day 0), and pregnant (Days 1.5, 2, 3, 4, 6, and
      16) ewes were analyzed with light and electron microscopy. The mean cell height
      of epithelial cells from estrus and from Days 1.5, 2, and 3 of pregnancy was
      significantly (p < 0.05) higher than in ovx animals. A significant reduction in
      cell height was observed at Day 4 of pregnancy, and this value remained unchanged
      at Day 6 and Day 16. Ciliated and nonciliated cells were present in the ampulla
      at all stages examined, with ciliated cells constituting the major cell type.
      Consistent with previous results, the nonciliated cells obtained from ovx ewes
      were synthetically inactive and at estrus were characterized by well-developed
      secretory organelles, including abundant amounts of secretory granules containing
      the E2-dependent glycoprotein. Extensive microvilli and cytoplasmic blebs
      protruding into the oviduct lumen distinguished the apical surface of secretory
      epithelial cells until Day 3. At Day 1.5 the secretory cells contained dilated
      cisternae of rough endoplasmic reticulum and enlarged Golgi, which were
      progressively diminished with increasing stages of pregnancy. Exocytosis, fusion
      of secretory granules, and a reduction in their electron density were seen until
      Days 3-4. By Day 4 and Day 6, fewer granules were observed in the ampulla
      cytoplasm and few, if any, were present by Day 16. Increases in the amount of
      heterochromatin were seen in nuclei at Day 6 and Day 16. Extrusion of epithelial
      cells into the oviduct-lumen was evident at Day 16 of pregnancy. These data show
      that 1) the secretory epithelium of the sheep ampulla oviduct undergoes
      morphological alterations in protein-synthesizing organelles and apical
      specializations that vary with the stage of pregnancy, 2) the secretory product
      contained in lamellar granules is released by the process of exocytosis until
      Days 3-4, and 3) cell death appears to occur at Day 16 by shedding of epithelial
      cells into the oviduct lumen.

PMID- 7578689
TI  - Rotational dynamics of luteinizing hormone receptors on bovine and ovine luteal
      cell plasma membranes.
AB  - To determine whether LH receptor rotational diffusion is similar in closely
      related species, we compared the rotational correlation times of LH receptors on
      bovine CL membranes with those of LH receptors on sheep small luteal cells and
      luteal cell plasma membranes using time-resolved phosphorescence anisotropy
      techniques. After binding of erythrosin isothiocyanate (ErITC)-derived bovine LH
      (bLH), ErITC-ovine LH (oLH), or ErITC-hCG, there was no difference in the initial
      and final anisotropy at 4 degrees C, 15 degrees C, 25 degrees C, and 37 degrees
      C, indicating that the bLH receptor was rotationally immobile on the time scale
      of our experiments. On these same membrane preparations, the epidermal growth
      factor (EGF) receptor occupied by ErITC-murine EGF exhibited temperature
      dependent rotational correlation times of 80 +/- 5 microseconds, 111 +/- 7
      microseconds, 254 +/- 4 microseconds, and > 1000 microseconds at 4 degrees C, 15
      degrees C, 25 degrees C, and 37 degrees C, respectively. Slower rotational times
      for EGF receptor observed at higher temperatures suggested the occurrence of
      temperature-dependent receptor aggregation. Like the bLH receptor, the oLH
      receptor on intact cells and on CL plasma membranes was rotationally immobile on
      the time scale of our experiments when occupied by ErITC-hCG. However, the oLH
      occupied receptors on small luteal cells and on luteal cell membranes had
      comparable rotational correlation times at 37 degrees C. These results suggest
      that bLH receptors are present in large, rotationally immobile structures,
      whereas the receptor-containing structure formed on ovine luteal cells depends on
      whether that receptor is occupied by hCG or oLH. Also, despite the similarities
      between reproductive function in these species, the LH-occupied receptor appears
      to be organized differently in the plasma membranes of these hormone-responsive
      luteal cells.

PMID- 7578692
TI  - Regulation of cumulus cell steroidogenesis by the porcine oocyte and preliminary
      characterization of oocyte-produced factor(s).
AB  - This study was designed to investigate whether porcine oocytes produce a
      factor(s) that influences cumulus and mural granulosa cell steroid production and
      to characterize the biochemical nature and mode of action of a such factor(s).
      Porcine cumulus-oocyte complexes (COC) were collected from 2-5 mm follicles and
      cultured either intact or after oocytectomy for 48 h. Steroid levels were then
      measured in the culture media. Conditioned media, obtained by culturing denuded
      oocytes for 48 h, were subjected to heat treatment of charcoal extraction and
      utilized to culture intact and oocytectomized COC. FSH-stimulated progesterone,
      20 alpha-OH-progesterone, and estradiol were significantly higher in
      oocytectomized vs. intact COC cultures. Denuded oocytes cultured with granulosa
      cells significantly inhibited progesterone production compared to control. Also,
      media conditioned with different numbers of denuded oocytes (0 to 300)
      significantly inhibited progesterone production by oocytectomized COC in a manner
      dependent on oocyte number. Charcoal extraction, but not heat treatment,
      significantly removed the inhibitory effect of the conditioned media on
      progesterone production by oocytectomized COC. Increased progesterone production
      by oocytectomized COC was not accompanied by a similar increase in cAMP
      formation. Heptanol, a gap junction blocker, did not alter progesterone
      production by intact COC. In conclusion, porcine oocytes secrete a factor(s) that
      inhibits cumulus and mural granulosa cell steroidogenesis. This factor(s) is heat
      stable but extractable by charcoal. The factor(s) appears not to be transferred
      to somatic cells via gap junctions, and its effect is downstream of cAMP
      formation.

PMID- 7578691
TI  - Effect of in vivo gonadotropin treatment on the ability of progesterone,
      estrogen, and cyclic adenosine 5'-monophosphate to inhibit insulin-dependent
      granulosa cell mitosis in vitro.
AB  - The ability of progesterone (P4), estradiol-17 beta (E2), and 8-bromo (br)-cAMP
      to inhibit small granulosa cells (GCs) from undergoing insulin-dependent mitosis
      was examined. Small GCs were isolated from immature and eCG-primed rats and
      separated by Percoll fractionation. Small GCs were cultured for 24 h with various
      combinations of insulin, steroids, steroid receptor antagonists, and 8-br-cAMP.
      Before and after culture, the number of GCs was counted. Small GC proliferation
      was expressed as a percentage increase over the initial value P4 inhibited
      insulin-dependent mitosis of small GCs isolated from both immature and eCG-primed
      rats. The effects of P4 were dose-dependent, steroid-specific, and reversed by
      the progesterone antagonist RU486. E2 inhibited insulin-dependent mitosis of
      small GCs isolated from immature but not eCG-primed rats. The action of E2 was
      dose-dependent and inhibited by the estrogen antagonist tamoxifen. Additional
      studies were conducted in which small GCs from immature rats were cultured with
      insulin in the presence of both P4 and E2 and their respective antagonist. Both
      antagonists were required for insulin to induce GC mitosis in the presence of P4
      and E2. Further, the ability of P4 to suppress insulin-dependent mitosis was
      reduced if it was not present during the first 6 h of culture. In contrast, E2
      could be added up to 12 h after insulin exposure and still completely prevent GC
      mitosis. 8-br-cAMP also prevented insulin-dependent GC proliferation. The actions
      of 8-br-cAMP could not be reversed by aminoglutethimide or RU486.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578694
TI  - Expression and activity of ovarian tissue inhibitors of metalloproteinases during
      pseudopregnancy in the rat.
AB  - The present study examined the role of tissue inhibitors of metalloproteinases
      (TIMPs) in tissue remodeling that occurs during luteal development and regression
      throughout pseudopregnancy in the rat. Pseudopregnancy was induced in immature
      female rats by eCG/hCG priming. Animals (n = 4 per time point) were killed on
      Days 1, 2, 4, 8, 12, 14, and 16 of pseudopregnancy (post hCG administration), and
      ovaries were removed and analyzed for metalloproteinase inhibitor activity or
      TIMP-1, TIMP-2, and TIMP-3 mRNA expression. Inhibitory activity was highest in
      Day-1 samples (41.35 +/- 6.50 inhibitory units), and inhibitor activity
      significantly decreased (p < 0.05) thereafter to minimal values at Day 12 (8.14
      +/- 2.71 inhibitory units). Methylamine hydrochloride treatment, which
      inactivates macroglobulin-type inhibitors, revealed that the majority of the
      inhibitor activity in the Day-1 samples (82.6%) and the Day-16 samples (77.3%)
      could be attributed to TIMPs. To further distinguish the contribution of each
      TIMP to this activity, Northern analysis for TIMP-1, -2, and -3 was performed.
      Analysis of TIMP mRNA expression revealed that TIMP-1 transcript expression was
      highest (p = 0.00009) at Day 1, decreased approximately 3- to 20-fold from Days 2
      to 12, respectively, and again increased at Days 14-16. However, TIMP-2
      expression did not change (p > 0.05) over any of the time points studied. In
      contrast to TIMP-1 and TIMP-2 expression, TIMP-3 mRNA expression was lowest
      during Days 1 and 2 of pseudopregnancy, increased approximately 4-fold at Day 4,
      peaked at Day 8, and remained elevated throughout the remainder of
      pseudopregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578693
TI  - Studies of porcine and human sperm suggesting a role for a sperm glycine
      receptor/Cl- channel in the zona pellucida-initiated acrosome reaction.
AB  - It is known that Cl- is required for the zona pellucida (zona)- and progesterone
      initiated mammalian sperm acrosome reaction (AR). Recent evidence indicates the
      involvement of a unique progesterone receptor resembling a GABAA receptor/Cl-
      channel in the latter event. In the study reported here, we investigated whether
      the in vitro porcine sperm AR initiated by heat-solubilized porcine zonae
      involves a different receptor/Cl- channel than does the progesterone-initiated
      AR. Capacitated porcine sperm failed to undergo the zona- and progesterone
      initiated AR when suspended in a medium deficient in Cl-. We then employed 1)
      strychnine, an antagonist of neuronal glycine receptor/Cl- channels at nanomolar
      concentrations and of GABAA receptor/Cl- channels at micromolar concentrations
      and 2) (+)-bicuculline, an antagonist of neuronal GABAA receptor/Cl- channels
      that inhibits glycine receptor/Cl- channels only at higher concentrations. We
      report here that the zona-initiated AR was inhibited by 50 nM strychnine, but the
      progesterone-initiated AR required 1 microM for inhibition. Moreover, 1 microM
      (+)-bicuculline inhibited the progesterone-initiated AR, but the zona-initiated
      AR required 50 microM for inhibition. In addition, glycine initiated the porcine
      sperm AR, and that event was inhibited by strychnine and (+)-bicuculline with the
      same order of potency observed for the zona-initiated AR. Finally, glycine
      initiated the AR in human sperm, and that initiation was inhibited by 50 nM
      strychnine. This work provides the first evidence suggesting that a glycine
      receptor/Cl- channel is involved in the zona-initiated mammalian sperm AR.

PMID- 7578697
TI  - Testis-brain RNA-binding protein, a testicular translational regulatory RNA
      binding protein, is present in the brain and binds to the 3' untranslated regions
      of transported brain mRNAs.
AB  - Previous studies have demonstrated that a phosphoprotein in testis binds to
      transcript c, a sequence containing two highly conserved elements, Y and H, in
      the 3' untranslated region (UTR) of mouse protamine 2 mRNA (mP2) and represses
      its translation in vitro. When gel-retardation assays were performed with
      cytoplasmic extracts prepared from seven different mouse tissues, we found that
      brain in addition to testis contains a protein that binds to transcript c. Both
      the testis and brain proteins are found exclusively in the nonpolysomal fractions
      of their postmitochondrial extracts. The testis and brain proteins appear to be
      identical according to numerous criteria: the complexes they form with transcript
      c have identical mobility in native gels, identical optimal pH, identical
      lability to increased salt concentrations, identical chromatographic properties,
      identical molecular sizes as judged from UV crosslinking, and identical peptide
      mapping as revealed by V8 digestion of the UV crosslinked protein-RNA complexes.
      In addition to binding to the same conserved sequence in the 3'UTR of mP2, the
      phosphoprotein from testis and brain, hereafter called testis-brain RNA-binding
      protein (TB-RBP), also specifically binds to a similar sequence in the 3'UTR of
      brain Tau mRNA. Since TB-RBP binds to the 3'UTRs of several translationally
      regulated mRNAs in testis and since numerous transported brain mRNAs also contain
      the same conserved binding elements, we propose that TB-RBP plays a role in mRNA
      storage, translocation, and/or localization in brain and testis.

PMID- 7578695
TI  - Potential role of mitogen-activated protein kinase in pronuclear envelope
      assembly and disassembly following fertilization of mouse eggs.
AB  - Changes in the activities of the p34cdc2/cyclin B complex and mitogen-activated
      protein (MAP) kinase were analyzed after insemination of mouse eggs in vitro.
      Whereas histone H1 kinase activity (p34cdc2/cyclin B) fell to negligible levels
      by 90 min postinsemination, a decrease to negligible levels of myelin basic
      protein kinase activity (i.e., MAP kinase) was not observed until about 7 h
      postinsemination. The decrease in MAP kinase activity appeared to be linked to
      the prior decline in p34cdc2/cyclin B kinase activity, since inhibiting the
      fertilization-induced destruction of cyclin B by treating eggs with the
      microtubule inhibitor nocodazole prevented the decrease in each of these protein
      kinases; an intact spindle is required for cyclin destruction. Moreover,
      experimental elevation of MAP kinase activity by okadaic acid treatment under
      conditions that maintain negligible levels of p34cdc2/cyclin B kinase activity
      suggested that MAP kinase could be involved in pronuclear envelope dynamics.
      Specifically, preventing the fertilization-induced decrease in MAP kinase
      activity was correlated with inhibiting pronucleus formation, and elevating MAP
      kinase activity subsequent to pronucleus formation resulted in precocious
      pronuclear envelope breakdown prior to entry into M phase.

PMID- 7578696
TI  - Urinary 3 alpha,17 beta-androstanediol glucuronide is a measure of androgenic
      status in Eld's deer stags (Cervus eldi thamin).
AB  - To determine the primary excretory by-products of testosterone (T), 85 microCi
      [3H]T was administered i.v. to two adult Eld's deer stags. Blood (10 ml) was
      collected by jugular venipuncture at 0, 5, 10, 15, 30, 45, 60, 90, 120, 150, 180,
      240, and 480 min after isotope infusion, and all urine and feces were collected
      for 96 h after injection. Seventy percent of labeled circulating steroid was
      conjugated by 30 min postinfusion. The majority (80.4 +/- 3.2%) of T metabolites
      were excreted into urine, and 95.0 +/- 0.9% of these were conjugated, 95.8 +/-
      0.2% being hydrolyzable with glucuronidase. Seven urinary androgen metabolites,
      including androstanediol (5 alpha-androstan-3 alpha-17 beta-diol and 5 beta
      androstan-3 alpha-17 beta-diol), were identified in glucoronidase-hydrolyzed,
      ether-extracted Eld's deer urine pools after gas chromatography/mass
      spectrometry. A double-antibody 125I RIA for 5 alpha-androstanediol-3 alpha, 17
      beta-diol,17-glucuronide (3 alpha-diol-G) was validated for unprocessed urine.
      Longitudinal assessments of urine samples collected from 13 stages for 3 yr
      revealed biological concordance between fluctuations in urinary 3 alpha-diol-G
      and serum T, as well as seasonal changes in secondary sexual characteristics.
      Overall correlation between "same-day" matched serum T and urinary 3 alpha-diol-G
      was 0.58, (n = 6; p < 0.001). Thus, monitoring urinary 3 alpha-diol-G provides a
      noninvasive, alternative method for characterizing male endocrine
      interrelationships in an endangered ungulate species.

PMID- 7578699
TI  - Blockade of singular follicle-stimulating hormone secretion and testicular
      development in photostimulated Djungarian hamsters (Phodopus sungorus) by a
      gonadotropin-releasing hormone antagonist.
AB  - Photostimulated male Djungarian hamsters following placement in a long-day
      photoperiod exhibit a characteristic rise in serum FSH levels that occurs in the
      absence of a simultaneous rise in LH levels. It is not known whether this
      singular FSH secretion is dependent upon a differential responsiveness of the
      gonadotrophs to the pattern of pulsatile GnRH release or is instead driven by a
      GnRH-independent mechanism. We have assessed the GnRH dependence of this singular
      FSH secretion by testing the ability of a potent GnRH antagonist (GnRHa: WY
      45760) to block FSH and testicular responses to photostimulation. Photoinhibited
      hamsters were transferred from a short-day (6L:18D) to a long-day photoperiod
      (16L:8D). Hamsters received two daily injections of a GnRH antagonist or vehicle
      (VEH). After 0 (short day), 3, 5, 10, 30, or 40 days the hamsters were killed;
      plasma was assayed for FSH, LH, and testosterone (T), and testes weights were
      recorded. Testes were sectioned and analyzed for tubular development. In VEH
      treated animals, testicular weights increased after photostimulation, reaching
      mean values of 514 mg by 30 days. Treatment with GnRHa resulted in a significant
      (p < 0.01) attenuation of testicular growth after 30 days of photostimulation
      (mean testes weight = 110.1 mg). In VEH-treated hamsters there was a rapid
      increase in FSH levels after photostimulation that became significant by 5 days
      and peaked at 10 days. In the GnRHa-treated group, however, these FSH increments
      were completely blocked at 5 days and significantly reduced at 10 days compared
      to the values in the corresponding VEH-treated groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7578701
TI  - [Social representation of labels associated to mental illness].
AB  - The social context linked to deinstitutionalization brought the authors to study
      the impact of labels placed on people having undergone psychiatry. The objective
      of this research is to better understand the subtleties made by the public
      concerning the following terms: the mentally ill person (malade mental), the ex
      psychiatric patient (ex-patient psychiatrique) and the person suffering from a
      mental health problem (personne souffrant d'un probleme de sante mentale). Data
      collected from 255 francophone residents from the Montreal area show that the
      expression "ex-psychiatric patient" is less stigmatizing than the expressions
      "mentally ill person" or "person suffering from a mental health problem" (PSMHP),
      as it refers to a past event that is over and done with. The expression "mentally
      ill person" emphasizes the chronic nature of the health problem suffered by the
      individual, where as the PSMHP focuses on the person's potential for recovery.
      The expression "ex-psychiatric patient" points to the capacity to function
      normally in society.

PMID- 7578698
TI  - Estrogen uncouples steroidogenesis from 3',5'-cyclic adenosine monophosphate
      regulation in the rabbit corpus luteum.
AB  - The hypothesis was investigated that estradiol, the luteotrophic hormone in the
      rabbit, uncouples luteal progesterone production from regulation by LH/cyclic
      AMP. Progesterone production by corpus luteum (CL) incubated with vehicle, 3
      isobutyl-1-methyl-xanthine (IBMX), hCG, or hCG+IBMX was compared in
      pseudopregnant rabbits treated continuously with estradiol (estradiol
      maintained), withdrawn from estradiol for 24-48 h (estradiol-withdrawn), or
      withdrawn and then replaced with estradiol for 6 or 24 h (estradiol-replaced).
      Progesterone production in estradiol-maintained rabbits was not altered by hCG
      and/or IBMX, but was stimulated significantly in estradiol-withdrawn rabbits.
      This response was reversed (i.e., abolished) in estradiol-replaced (24 h)
      rabbits. The loss of responsiveness to hCG was not attributable to impaired
      accumulation of cyclic AMP: basal and hCG-stimulated cyclic AMP concentrations
      were similar in luteal tissues of estradiol-maintained and estradiol-withdrawn
      rabbits. The loss of responsiveness to hCG was also not a consequence of maximal
      progesterone production: CL of estradiol-replaced (6 h) rabbits were also
      insensitive to hCG, and this occurred before progesterone production attained a
      maximal rate. We conclude that a striking feature of the luteotrophic action of
      estrogen is to uncouple the regulation of progesterone production from cyclic
      AMP.

PMID- 7578700
TI  - Ovine interferon-tau regulates expression of endometrial receptors for estrogen
      and oxytocin but not progesterone.
AB  - Ovine interferon-tau (oIFN-tau) may stabilize endometrial progesterone receptor
      (PR) and/or inhibit estrogen receptor (ER) gene expression during pregnancy
      recognition to suppress endometrial oxytocin receptor (OTR) formation and
      production of luteolytic prostaglandin (PG) F2 alpha pulses. This study
      determined whether or not oIFN-tau stabilized PR expression in the endometrium
      during PR down-regulation by continuous exposure to progesterone. Twenty cyclic
      ewes were bilaterally ovariectomized and fitted with uterine catheters on Day 2
      of the estrous cycle (Day 0 = estrus). Ewes were then assigned randomly to be
      treated, in a 2 x 2 factorial arrangement, with recombinant oIFN-tau (roIFN-tau;
      2 x 10(7) antiviral units per ewe per day) or control proteins (6 mg/day) by
      intrauterine injection from Days 10 to 14, and with daily i.m. injections of 20
      mg progesterone from Days 2 to 14 (P) or progesterone from Days 2 to 14 plus 50
      micrograms estradiol-17 beta from Days 12 to 14 (P+E). All ewes were
      hysterectomized on Day 15. Endometrial PR mRNA (p < 0.01) and protein (p < 0.03)
      were higher in ewes receiving P+E than in those receiving P alone. However, the
      increase in PR mRNA and protein was not as great in the endometrium of roIFN-tau
      treated ewes as compared to controls (p < 0.08, treatment x steroid). In ewes
      receiving P alone, PR mRNA and immunoreactive PR were localized to stroma and
      deep glandular epithelium and were not present in endometrial luminal and shallow
      glandular epithelium. Values for endometrial ER mRNA (p < 0.02) and ER protein (p
      < 0.01) were greater in controls than in roIFN-tau-treated ewes regardless of
      steroid treatment. Among controls, ER mRNA and immunoreactive ER protein were
      present in the luminal and glandular epithelium and were increased in the
      epithelium and stroma in ewes receiving estrogen. In contrast, endometrial ER
      mRNA and immunoreactive ER protein were very low or absent in the endometrium of
      roIFN-tau-treated ewes and were not increased by estrogen. Among controls,
      endometrial OTR density was greater (p < 0.09) in ewes treated with P+E than in
      those treated with P alone. In roIFN-tau-treated ewes, endometrial OTR density
      was lower (p < 0.01) than in the controls. Results indicate that roIFN-tau did
      not stabilize or prevent autologous down-regulation of PR mRNA or protein
      expression in the endometrium. However, roIFN-tau did suppress endometrial ER
      expression and OTR formation in ewes regardless of steroid treatment. The results
      support the hypothesis that the antiluteolytic effects of oIFN-tau are to
      suppress endometrial ER gene expression in the endometrial epithelium, thereby
      inhibiting formation of OTR and production of luteolytic PGF2 alpha pulses.

PMID- 7578704
TI  - [The place of emotions in psychology and their role in conversational exchanges].

PMID- 7578702
TI  - [Psychological distress of recent university graduates who are victims of
      prolonged unemployment].

PMID- 7578703
TI  - [Mental health policies and the transfer of services to the community].
AB  - In this article, the mental health policy is viewed as a pivotal element of the
      "psychiatric services" reform which began in Quebec in the seventies. The authors
      advance the hypothesis that the community approach has played a fundamental role
      in developing the reform and that it has itself undergone deep changes. As a
      result, the policy's and the reform's effects are discussed from two angles,
      namely that of the communitization of services and that of the direction taken by
      the community approach during the reform process.

PMID- 7578705
TI  - [Social rehabilitation of psychiatric patients in the province of Parma, Italy].

PMID- 7578706
TI  - [The "Entreparents" program: furnishing parents the means to help their children
      to adapt to their separation].

PMID- 7578707
TI  - [From one ear to the other ... words, an alternative practice to psychiatry].

PMID- 7578708
TI  - [Prolonged action neuroleptics and the relationship between physician, patient
      and family].

PMID- 7578709
TI  - [Developing services for patients who need long-term care].
AB  - Attempts at regional planning in the Outaouais have shown that it is difficult to
      open up mental health services for underprivileged clienteles that are more
      vulnerable. Nonetheless, services can be offered by developing partnerships
      between institutions and community groups, while ensuring that individual
      expertise and local differences are respected. However, the healthcare and social
      services network must learn how to build intersectorial mechanisms that can
      change the socio-economic conditions which explain the conditions of patients and
      their exclusion. With budget cuts in the background, the participation of
      citizens could make all the difference.

PMID- 7578710
TI  - [Mental health policy: regional activities. Considerations by someone involved].
AB  - Based on experiences at the local, regional and central level, the author
      provides a number of personal observations concerning regional initiatives
      brought on by Quebec's mental health policy.

PMID- 7578711
TI  - [The institutional policy concerning sexuality: the necessary transformation of
      the sexology paradigm].
AB  - An increasing number of hospitals and rehabilitation centres include sexuality in
      their mandate. Some of these establishments have developed a policy in this
      matter or would like to. Based on a study of recorded policies, the author
      discusses various aspects of these policies, including legitimacy, necessity,
      content and implementation. Most policies under study are built around the notion
      that sexuality is a problem. The policy is therefore designed as an instrument
      for normalization and social control. The author proposes another paradigm: that
      which envisions sexuality positively by emphasizing the need to improve one's
      quality of sex life. As a result, policies would be more attuned to the meaning
      of sexuality rather than to sexual norms and rules. The author argues that such a
      concept widens the scope of institutional policy, from sexuality-as-a-problem to
      sexuality-as-a-health-issue.

PMID- 7578712
TI  - [The mirage of technological innovation].

PMID- 7578713
TI  - [Changes in French mental health policy].
AB  - Following psychiatry's turning point in 1960, as well as very slow progress in
      the establishment of a sectorial policy, these last few years have been
      characterized by the increased production of reports that aim to organize
      France's mental health policy in a coherent fashion. Meanwhile, thought on the
      issue has taken on a broader scope. The mental health issue is no longer limited
      to the structural modernization of the field of psychiatry, in the sense of
      remaining within traditional boundaries. From this approach arise two strategic
      orientations designed to let go patients and arise two strategic orientations
      designed to let go patients and find therapeutic responses from an institutional
      environment that has long kept to itself. The first orientation deals with
      mechanisms that are based in social support interventions, while the second
      focuses on integrating psychiatry in general hospitals. Faced with this
      bipolarization, how will psychiatric institutions fit in the overall scheme of
      things?

PMID- 7578715
TI  - Leptospirosis.

PMID- 7578714
TI  - [Mothers of psychotic patients and their difficulties with the health care
      system].
AB  - This article describes the difficulties perceived by mothers of people suffering
      from psychotic problems when coping with the healthcare system. The 99
      interviewees were recruited through mutual help groups and hospitals. In addition
      to feeling left to themselves to care for their child, their main grievances
      relate to the fact that their child does not have access to workforce integration
      resources, that therapeutic follow-up (non-drug related) is inadequate and that
      they do not receive updates on the state of health of their child. Mothers
      belonging to mutual help groups are significantly more upset about the
      difficulties they encounter when coping with the healthcare system, in comparison
      to mothers who do not belong to such groups. In light of comments by experts and
      the interviewees, the authors make suggestions designed to improve existing
      services, as well as collaboration between healthcare teams and the families
      concerned.

PMID- 7578716
TI  - Blastocystis hominis and traveler's diarrhea.

PMID- 7578717
TI  - Is there any reason to continue treating Blastocystis infections?

PMID- 7578718
TI  - Factors associated with the development of Pneumocystis carinii pneumonia in
      5,025 European patients with AIDS. AIDS in Europe Study Group.
AB  - This study examined the factors associated with the development of a first
      episode of Pneumocystis carinii pneumonia (PCP) in 5,025 patients with AIDS,
      including 1,976 patients with primary PCP at the time of AIDS diagnosis and 635
      with primary PCP occurring subsequently. Compared with untreated patients,
      patients treated with zidovudine were at similar risk of developing PCP during
      the first year of therapy but were at greater risk after longer intervals of
      treatment. The following factors were associated with an increased risk of PCP
      (either at the time of AIDS diagnosis or thereafter): lack of primary PCP
      prophylaxis, male homosexuality/bisexuality, diagnosis of AIDS in northern
      Europe, and CD4 cell count below 200 x 10(6)/L at the time of AIDS diagnosis.
      Patients with severe weight loss had a 60% higher risk of developing PCP during
      follow-up than those without such weight loss. Thus, the occurrence of PCP
      depended on geographic location, mode of acquisition of human immunodeficiency
      virus and AIDS, degree of immunodeficiency, and use of various treatment
      regimens.

PMID- 7578719
TI  - A prospective study of daily measurement of C-reactive protein in serum of adults
      with neutropenia.
AB  - A total of 1,622 daily measurements of the level of C-reactive protein (CRP) in
      the serum of 40 hospitalized patients with neutropenia were made during 55 study
      periods from October 1990 through February 1993 (mean, 29.5 measurements per
      period). Clinical events were categorized into four groups: group I (bloodstream
      infection), group II (significant bacterial or fungal infection without
      bloodstream infection), group III (fever without an obvious source), and group IV
      (drug-related fever). There was a strong association between baseline elevation
      of the CRP level (> or = 100 mg/L) and tumor-associated fever (P = .0005); the
      resolution of such fever coincided with a decrease in the CRP level following
      chemotherapy. Levels of CRP increased by > or = 40 mg/L in 10 (31%) of 32 cases
      during the 48-72 hours preceding the clinical diagnosis of a subsequently
      demonstrable infection--often pneumonia without bloodstream infection. CRP values
      on day 2 (1 day after the diagnosis of a clinical event) were significantly
      higher for events in groups I and II than for those in group III (P < .01) but
      not those in group IV. With regard to significant infections, a day-2 CRP value
      of > or = 40 mg/L was 100% sensitive and an increase in CRP level of > or = 50
      mg/L from day 1 to day 2 had a positive predictive value of 95%. We conclude that
      serial measurements of serum CRP levels may be helpful in determining the extent
      of evaluation required for a newly febrile neutropenic patient and possibly in
      accelerating the detection of an otherwise unsuspected infection.

PMID- 7578720
TI  - Failure of culture and polymerase chain reaction to detect human immunodeficiency
      virus (HIV) in seronegative steady sexual partners of HIV-infected individuals.
AB  - Because of concern that steady sexual partners of patients infected with human
      immunodeficiency virus (HIV) may be infected despite negative results in tests
      for antibody to HIV, we studied 50 sexually active couples with discordant
      antibody results, assessing the agreement between these serological results and
      those obtained by p24 antigen testing, the polymerase chain reaction (PCR), and
      culture. Forty-nine of 50 seropositive sexual partners were also positive for HIV
      by PCR; the remaining seropositive partner was positive by culture. All
      seronegative partners also had negative results in the other three tests.
      Moreover, seronegative partners continued to have negative results in all tests
      for a mean follow-up period of 17 months despite ongoing sexual relations with
      their seropositive partners. Seronegative infection was not documented in these
      partners at risk for sexual transmission of HIV. HIV-negative individuals in
      stable, monogamous sexual relationships with HIV-infected partners apparently do
      not have a high incidence of infection despite continued sexual exposure.

PMID- 7578721
TI  - Clinical significance of nontuberculous mycobacteria isolates in a Canadian
      tertiary care center.
AB  - To determine the epidemiology and clinical features of disease due to
      nontuberculous mycobacteria (NTM) in our institution, we reviewed the medical
      records of all patients from whom NTM isolates were recovered from 1988 to 1990
      to extract selected clinical and laboratory data. On the basis of the likelihood
      of infection, patients were classified as having definite, probable, or unlikely
      NTM disease as defined by published guidelines. Of 80 patients who met the
      inclusion criteria, 17 had definite NTM disease, and 23 had probable NTM disease.
      No differences in age, sex, presence of underlying pulmonary or nonpulmonary
      disease, or chest radiographic abnormalities were noted between patients with and
      without NTM disease. More than 85% of all definite or probable cases were caused
      by Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium
      fortuitum complex. The diagnosis of NTM disease was often delayed or missed,
      which resulted in unsatisfactory management of patients. There is a need to
      educate physicians about the diagnosis and management of NTM infections.

PMID- 7578722
TI  - Prosthetic joint infection due to Mycobacterium tuberculosis: report of three
      cases.
AB  - Prosthetic joint infection due to Mycobacterium tuberculosis is uncommon. We
      describe three patients with delayed tuberculous prosthetic joint infection and
      review the eight other cases reported in the English-language literature.
      Infection results from local reactivation, which can occur up to 40 years after
      the initial infection, or from hematogenous spread. The diagnosis is often
      delayed because it is not considered in the initial evaluation, because it is
      difficult to confirm microbiologically, or because other bacteria may be isolated
      from the synovial fluid and thus be considered the etiology of the infection.
      Treatment usually consists of removal of the prosthesis in addition to
      administration of antituberculous agents.

PMID- 7578724
TI  - Return to the past: the case for antibody-based therapies in infectious diseases.
AB  - In the preantibiotic era, passive antibody administration (serum therapy) was
      useful for the treatment of many infectious diseases. The introduction of
      antimicrobial chemotherapy in the 1940s led to the rapid abandonment of many
      forms of passive antibody therapy. Chemotherapy was more effective and less toxic
      than antibody therapy. In this last decade of the 20th century the efficacy of
      antimicrobial chemotherapy is diminishing because of the rapidly escalating
      number of immunocompromised individuals, the emergence of new pathogens, the
      reemergence of old pathogens, and widespread development of resistance to
      antimicrobial drugs. This diminishment in the effectiveness of chemotherapy has
      been paralleled by advances in monoclonal antibody technology that have made
      feasible the generation of human antibodies. This combination of factors makes
      passive antibody therapy an option worthy of serious consideration. We propose
      that for every pathogen there exists an antibody that will modify the infection
      to the benefit of the host. Such antibodies are potential antimicrobial agents.
      Antibody-based therapies have significant advantages and disadvantages relative
      to standard chemotherapy. The reintroduction of antibody-based therapy would
      require major changes in the practices of infectious disease specialists.

PMID- 7578725
TI  - Pyoderma fistulans sinifica (fox den disease): a distinctive soft-tissue
      infection.
AB  - Pyoderma fistulans sinifica (PFS, also referred to as fox den disease because its
      multiple fistulae and sinuses resemble the structure of a fox den) is a distinct
      chronic infectious disease in which epithelialized tracts form within the
      subdermal fatty tissue. PFS, which has not been previously described in the
      English-language literature, must be differentiated from hidradenitis
      suppurativa, pilonidal sinus, and perianal fistula. The fistulous tracts of PFS
      are always lined by stratified squamous-cell epithelium but, unlike those of
      hidradenitis, reach deep into the subcutaneous fat, run epifascially for long
      distances, and have no relation to skin appendices. We report on 10 men (mean age
      +/- SD, 36 +/- 5 years) with PFS (mean duration +/- SD, 11 +/- 7 years).
      Bacterial cultures of affected tissue from these patients yielded a total of 14
      facultative and 31 obligate anaerobic species. Treatment consisted of wide en
      bloc excision down to the fascia, including all fistulae. Antibiotic therapy
      temporarily reduced purulent discharge but did not eradicate the infection. Two
      patients who underwent fistulotomy without wide en-bloc excision developed
      recurrences.

PMID- 7578723
TI  - Sinonasal non-Hodgkin's lymphoma in patients infected with human immunodeficiency
      virus: report of three cases and review.
AB  - Non-Hodgkin's lymphoma (NHL) is a frequent complication of human immunodeficiency
      virus (HIV) infection, but involvement of the sinonasal region has only rarely
      been reported. We report three cases of AIDS-associated sinonasal NHL that
      occurred at our institution and review eight cases that were reported in the
      literature. The epidemiological and clinicopathologic features of these cases are
      described and compared with those of three other groups of patients: non-HIV
      infected patients with sinonasal NHL, HIV-infected patients with NHL of any
      anatomic site, and HIV-infected patients with infectious sinusitis. Patients with
      AIDS-associated sinonasal NHL more frequently developed bony erosion and
      presented with signs and symptoms referable to adjacent structures, such as the
      orbit, than did HIV-infected patients with sinusitis, and patients with AIDS and
      NHL less frequently had typical sinus symptoms and diffuse sinus involvement than
      did patients with sinusitis. However, the clinical manifestations of these
      conditions overlap; thus a high index of suspicion for NHL is imperative for
      prompt diagnosis. These lymphomas typically are high-grade and disseminate early,
      and the prognosis is generally poor.

PMID- 7578726
TI  - Changes in the core tonsillar bacteriology of recurrent tonsillitis: 1977-1993.
AB  - Microbiological studies of the core of tonsils removed from children with
      recurrent tonsillitis due to group A beta-hemolytic streptococci were conducted
      during three periods, with 50 patients in each period: 1977-1978 (period 1), 1984
      1985 (period 2), and 1992-1993 (period 3). Mixed flora were present in all
      tonsils, with 8.1 organisms per tonsil (3.8 aerobes and 4.3 anaerobes). The
      predominant isolates in each period were Staphylococcus aureus, Moraxella
      catarrhalis, Peptostreptococcus species, pigmented Prevotella species,
      Porphyromonas species, and Fusobacterium species. The rate of recovery of
      Haemophilus influenzae type b increased from 24% in period 1 to 76% in period 2
      (P < .001); a decline to 12% in period 3 correlated with a concomitant increase
      in the frequency of recovery of non-type b strains of H. influenzae from 4% and
      10% in periods 1 and 2, respectively, to 64% in period 3 (P < .001). Both the
      rate of recovery of beta-lactamase-producing bacteria and the number of these
      organisms per tonsil increased over time. Specifically, beta-lactamase-producing
      strains were detected in 37 tonsils (74%) during period 1, in 46 tonsils (92%)
      during period 2, and in 47 tonsils (94%) during period 3, and the number of such
      strains per tonsil increased from 1.1 in period 1 to 2.9 and 3.3 in periods 2 and
      3, respectively.

PMID- 7578727
TI  - Incidence and pathogenicity of Arcanobacterium haemolyticum during a 2-year study
      in Ottawa.
AB  - Arcanobacterium haemolyticum has been described as a rare cause of systemic
      invasive disease and is occasionally isolated from throat swabs. We describe a 2
      year study of the incidence and clinical features of A. haemolyticus infection in
      a pediatric and adolescent population. A total of 11,620 throat swabs were
      examined for A. haemolyticum with use of a locally developed selective medium.
      Controls (2,241) were healthy students who were recruited from a separate study.
      A. haemolyticum was isolated from 42 patients, with the maximum incidence in the
      15 to 18-year-old age group; in this subset the incidence was 2.5%. There were no
      isolates of A. haemolyticum found in the healthy controls, and the difference in
      incidence between patients and controls in the 15 to 18-year-old age group was
      highly significant (P < .01). Approximately half of the patients infected with A.
      haemolyticum had a rash. In 5 patients, A. haemolyticum was associated with a
      positive monospot test. The organism was highly susceptible to erythromycin and
      less susceptible to penicillin. The evidence from this study suggests that A.
      haemolyticum may be a pathogen with maximum incidence in the 15 to 18-year-old
      age group.

PMID- 7578728
TI  - Purulent pericarditis caused by Candida species: case report and review.
AB  - Purulent pericarditis caused by Candida species is a rare and often undiagnosed
      disease. We recently treated a patient in whom purulent pericarditis due to
      Candida albicans developed following thoracic surgery. The patient survived after
      receiving a combination of surgical and medical therapy. A literature review
      revealed 24 additional cases of purulent pericarditis caused by Candida species.
      Twenty-one of the patients either had undergone thoracic surgery or had had
      disseminated candidiasis. None of the 12 patients described before 1980 survived,
      whereas six (46%) of the 13 patients described after 1980 survived. No patient
      survived without pericardiectomy (five of six survivors) or at least
      pericardiocentesis (one survivor). All survivors received full courses of
      amphotericin B therapy. An increased utilization of echocardiography, along with
      an increased recognition of the patient populations at risk, has been
      instrumental in early detection and improved outcome of purulent pericarditis. A
      combination of prolonged amphotericin B therapy and pericardiectomy appears to be
      the best approach for achieving a cure.

PMID- 7578730
TI  - Oral ciprofloxacin for treatment of infection following nail puncture wounds of
      the foot.
AB  - From January 1990 to December 1993, 23 adults were hospitalized at our
      institution for treatment of foot infections that occurred following nail
      puncture wounds. All 23 patients had cellulitis, and 14 had signs of
      osteochondritis on a roentgenogram or a 99mTc bone scan. After undergoing
      surgical intervention that consisted of debridement, drainage of the pus, and
      exploration of the bones, patients received intravenous ciprofloxacin (400 mg
      b.i.d.) for 24 hours, followed by an oral regimen (750 mg b.i.d.). Nine patients
      with cellulitis received oral therapy for 7 days, and the 14 patients with
      osteochondritis received oral therapy for 14 days. Isolates that were recovered
      included Pseudomonas aeruginosa (18 patients) and Staphylococcus aureus (2
      patients); one patient had a mixed infection, and in two cases no pathogens were
      recovered. All of the isolates were susceptible to ciprofloxacin. All patients
      were cured, and none had reinfection. Our results show that foot infection
      following a nail puncture wound may be treated with oral ciprofloxacin (750 mg
      b.i.d.) for 7-14 days, provided that surgery is performed first.

PMID- 7578729
TI  - Liposomal amphotericin B (AmBisome) in the treatment of complicated kala-azar
      under field conditions.
AB  - An open trial of liposomal amphotericin B (AmBisome [L-AmB]; Vestar, San Dimas,
      CA) for treatment of complicated visceral leishmaniasis was performed in Sudan.
      Forty-nine patients were treated, and there were six deaths (12% mortality);
      these were not attributed to therapy. Thirty-seven patients were selected for the
      trial because of (1) relapse after treatment with a combination of pentavalent
      antimony (Sbv) and aminosidine, (2) incomplete parasitological response to Sbv
      and aminosidine, or (3) severe illness. Drug regimen 1 (3 doses of 3-5 mg/kg, on
      days 0, 3, and 10) cured 8 (50%) of 16 patients; regimen 2 (6 doses of 3-5 mg/kg,
      on days 0, 3, 6, 8, 10, and 13) cured 14 (88%) of 16. For four of 10 partial
      responders, "rescue" therapy with L-AmB alone (3 mg/kg daily for 10 days)
      resulted in cure. Twelve less-unwell patients received regimen 3 (4 doses of 4-5
      mg/kg, on days 0, 2, 5, and 7); seven of 11 patients evaluated (64%) were cured.
      The optimal regimen of L-AmB in these circumstances is administration of 4 mg/kg
      on days 0, 3, 6, 8, 10, and 13.

PMID- 7578731
TI  - Mesangioproliferative glomerulonephritis and antibodies to phospholipids in a
      patient with acute Q fever: case report.
AB  - Glomerulonephritis is a rare complication of Q fever and is usually associated
      with the chronic form of disease, i.e., infectious endocarditis. We describe a 31
      year-old man with a self-limited acute febrile illness due to Coxiella burnetii
      infection who had acute renal failure secondary to mesangioproliferative
      glomerulonephritis. Antibodies to phospholipids were detected and suggested the
      diagnosis of Q fever in this case.

PMID- 7578732
TI  - Diagnosis of Legionella pneumophila infection by polymerase chain reaction.
AB  - We examined the application of the polymerase chain reaction (PCR) for the
      diagnosis of legionellosis. Eight intratracheal aspirates were collected from a
      patient with pneumonia caused by Legionella pneumophila serogroup 2, and serial
      10-fold dilutions of the samples were obtained. Two samples were positive for L.
      pneumophila by the direct fluorescent antibody (DFA) method down to a 10(-2)
      concentration, and one was positive down to a 10(-4) concentration. PCR was
      positive for all eight samples, and the sensitivity was greater than that of the
      DFA method. Only one of the eight samples yielded organisms in culture: the L.
      pneumophila serogroup 2 strain was isolated on buffered charcoal yeast extract
      alpha agar as an atypical white, papillate colony.

PMID- 7578733
TI  - Candidal brain abscess associated with vascular invasion: a devastating
      complication of vascular catheter-related candidemia.
AB  - We describe a patient who developed Candida albicans brain abscess associated
      with prominent vascular invasion following an episode of central venous catheter
      related fungemia. The increasing population of immunosuppressed patients and the
      frequent use of broad-spectrum antimicrobials, corticosteroids,
      chemotherapeutics, organ transplantation, and prolonged supportive measures are
      responsible for an increasing incidence of candidal infections. Brain abscess is
      a rare complication of candidemia but may be expected to become more common as
      venous catheter-related fungemia is encountered more frequently.

PMID- 7578734
TI  - Severe respiratory insufficiency complicating Epstein-Barr virus infection: case
      report and review.
AB  - We report a case involving a young adult who had life-threatening bilateral
      pneumonitis in the course of an acute Epstein-Barr virus (EBV) infection. Because
      of severe hypoxemia, the patient required mechanical ventilation and additional
      oxygenation by an intravascular oxygenator. The patient was treated with
      corticosteroids and survived without sequelae. Severe pulmonary involvement
      associated with EBV infection is a rare but potentially fatal complication of
      infectious mononucleosis. Similar cases reported in the literature are reviewed,
      and the therapeutic options for this particular complication are discussed.

PMID- 7578736
TI  - Bacteremia due to Haemophilus infections: a retrospective study with emphasis on
      the elderly.
AB  - We performed a retrospective study of all patients in a large health maintenance
      organization in Southern California who were identified as having positive blood
      cultures for Haemophilus organisms during a 20-month period (September 1990 to
      May 1992) to assess the incidence, presentation, and predisposing conditions of
      bacteremia due to these organisms and to examine some of the features of these
      infections in the elderly. Thirty-eight patients with bacteremia due to
      haemophilus infections were identified. Ten (26.3%) patients were 65 years of age
      or older. The incidence of bacteremic haemophilus infections in the elderly group
      was estimated at 2.7 per 100,000 individuals per year, which was almost three
      times greater than that for the younger age groups studied. When analyzed
      statistically, the presenting feature of the infection did not differ among age
      groups. Six patients died, four of whom were elderly. All six deaths were due to
      nontypable Haemophilus influenzae strains. Cancer was the only chronic underlying
      condition frequently found among the elderly patients. Three of 10 elderly
      patients lived in nursing homes; all three were infected with nontypable H.
      influenzae strains, and all three died.

PMID- 7578735
TI  - Renal aspergilloma due to Aspergillus flavus.
AB  - Renal aspergillomas have been reported only rarely. We report a case of
      Aspergillus flavus colonization of the renal pelvis and upper ureter of a patient
      with concomitant urinary schistosomiasis. The diagnosis was based on the
      demonstration of characteristic hyphal elements on direct microscopy and
      isolation of the fungus in culture. The patient was successfully treated with
      liposomal amphotericin B. This case emphasizes the importance of direct
      microscopic examination of urine specimens for prompt diagnosis of fungal
      infections of the urogenital system. Renal aspergilloma should be considered in
      the differential diagnosis of filling defects of the urinary tract, especially in
      patients who are immunocompromised.

PMID- 7578737
TI  - Granulomatous tophaceous gout mimicking tuberculous tenosynovitis: report of two
      cases.
AB  - Granulomatous inflammation in a tissue specimen raises concern about infection
      with Mycobacterium tuberculosis, atypical mycobacteria, certain fungi, Brucella
      species, and other infectious agents. Inflammatory disorders, such as
      sarcoidosis, crystal-associated arthritis, or foreign body reactions also are
      considered when granulomatous changes are seen on histological examination of a
      tissue specimen. We describe two cases of granulomatous tenosynovitis due to
      tophaceous deposits in patients with gout. In one case, tuberculous synovitis was
      considered the primary diagnosis until the diagnosis of gout was confirmed by
      examination of a tissue specimen with polarized light. In the second case, gout
      and tuberculosis were found in the patient's wrist joint. After antituberculous
      therapy was discontinued, he continued to have wrist synovitis and chronic
      drainage due to granulomatous tophaceous gout. The findings in this report
      suggest that gouty tenosynovitis can mimic tuberculous tenosynovitis and that
      gout should be considered in the differential diagnosis of granulomatous
      tenosynovitis, especially when acid-fast stains and cultures are negative for
      mycobacteria.

PMID- 7578738
TI  - High levels of interleukin 10 and tumor necrosis factor alpha in cerebrospinal
      fluid during the onset of bacterial meningitis.
AB  - Since interleukin-10 (IL-10) controls the production of tumor necrosis factor
      alpha (TNF-alpha) and this latter cytokine has a deleterious effect on neuronal
      cells, we determined the levels of both cytokines in cerebrospinal fluid (CSF)
      from children with bacterial meningitis. High levels of IL-10 (1,164 pg/mL) and
      TNF-alpha (3,158 pg/mL) were detected in CSF from 10 children with meningitis,
      but these cytokines were not detectable in CSF from 12 controls. In vitro
      neutralization of IL-10 demonstrated that endogenously formed IL-10 is important
      for limiting the production of TNF-alpha by leukocytes. We assume that IL-10 in
      CSF will decrease the inflammatory reaction associated with meningitis and will
      result in the development of fewer sequelae because of its inhibitory effect on
      the production of TNF-alpha.

PMID- 7578739
TI  - Use of vancomycin for the treatment of Corynebacterium xerosis pneumonia.

PMID- 7578741
TI  - Pulmonary infection due to Leuconostoc species in a patient with AIDS.

PMID- 7578740
TI  - Miliary liver abscesses and skin infection due to Yersinia enterocolitica in a
      patient with unsuspected hemochromatosis.

PMID- 7578742
TI  - Use of fluconazole is not associated with a higher incidence of Candida krusei
      and other non-albicans Candida species.

PMID- 7578743
TI  - Isolated gummatous splenitis.

PMID- 7578744
TI  - Esophageal leishmaniasis in a patient infected with the human immunodeficiency
      virus.

PMID- 7578745
TI  - Recurrent Streptococcus pyogenes pharyngitis due to an inadequately cleaned
      orthodontic appliance.

PMID- 7578746
TI  - Six cases in which mesenteric lymphadenitis due to non-typhi Salmonella caused an
      appendicitis-like syndrome.

PMID- 7578747
TI  - Septic shock due to Pasteurella multocida subspecies multocida in a previously
      healthy woman.

PMID- 7578748
TI  - Failure of cefotaxime treatment in a patient with penicillin-resistant
      pneumococcal meningitis and confirmation of nosocomial spread by random amplified
      polymorphic DNA analysis.

PMID- 7578749
TI  - Sepsis due to Clostridium perfringens after second-trimester amniocentesis.

PMID- 7578750
TI  - Bacteremia and suppurative lymphadenitis due to Yersinia enterocolitica in a
      neutropenic patient who prepared chitterlings.

PMID- 7578751
TI  - Diarrhea associated with Vibrio fluvialis infection in a patient with AIDS.

PMID- 7578753
TI  - Fatal toxic epidermal necrolysis in patients with AIDS.

PMID- 7578752
TI  - Liver abscess due to pyridoxal-dependent Streptococcus mitis.

PMID- 7578754
TI  - Cholera gravis caused by Vibrio cholerae O139, a novel, imported pathogen.

PMID- 7578755
TI  - Pitfalls of computerized literature searches.

PMID- 7578756
TI  - Clinical and host differences between infections with the two varieties of
      Cryptococcus neoformans.
AB  - A population-based register of cases of cryptococcosis in patients treated in
      Victoria, Australia, over a 10-year period was established for studying the
      epidemiologic and clinical features of infection with Cryptococcus neoformans and
      its two varieties, gattii and neoformans. One hundred thirty-three cases of
      cryptococcosis were entered on the register; the incidence was 3.0 cases per 1
      million population per year, a rate that increased to 5.0 cases per 1 million
      population per year over the decade as a result of the AIDS epidemic. There was a
      distinct association between immune status and C. neoformans variety: all C.
      neoformans variety gattii infections occurred in healthy hosts and 90% of C.
      neoformans variety neoformans infections occurred in immunosuppressed hosts.
      Meningitis was the commonest manifestation, with focal CNS and pulmonary lesions
      occurring primarily in healthy hosts with C. neoformans variety gattii infection;
      isolation of C. neoformans from blood and urine was associated with
      immunosuppression and C. neoformans variety neoformans infection. The mortality
      among patients with C. neoformans variety neoformans infection was high, while
      none of those patients with C. neoformans variety gattii died but often had
      neurological sequelae that required surgery and prolonged therapy. These findings
      appear to be related to variety-specific interactions between host and parasite
      and warrant further epidemiologic and immunologic study.

PMID- 7578757
TI  - Multiorgan microsporidiosis: report of five cases and review.
AB  - We describe five cases and review 34 reported cases of multiorgan
      microsporidiosis. Most of the patients with multiorgan involvement have been
      adults with AIDS. Organs most commonly infected include the small intestine,
      urinary tract, biliary tree, and eye; involvement of the respiratory tract, nasal
      sinuses, and central nervous system is also described but appears to be less
      frequent. Although patients with multiorgan disease may be asymptomatic, clinical
      presentation usually relates to the involved organs. Enterocytozoon bieneusi and
      Septata intestinalis are the most frequently identified species of pathogens. An
      affinity for certain tissues is observed among different microsporidial species.
      In all but one case of E. bieneusi infection, infection was limited to intestinal
      and hepatobiliary tracts, a finding suggestive of local extension. In contrast,
      the patients infected with S. intestinalis had widespread involvement, suggesting
      true hematogenous or lymphatic dissemination. Treatment may have to be based on
      findings regarding which organs and specific microsporidial species are involved.
      Further investigation of the pathogenic tendencies and route of acquisition of
      these organisms and the therapeutic agents active against them is needed.

PMID- 7578758
TI  - Stool carriage, clinical isolation, and mortality during an outbreak of
      vancomycin-resistant enterococci in hospitalized medical and/or surgical
      patients.
AB  - During a nosocomial outbreak of infection due to vancomycin-resistant enterococci
      (VRE), rectal swabs that were collected weekly were used to identify and isolate
      VRE carriers. Over 6 months, 1,458 stool specimens from 724 high-risk patients
      were cultured, and 187 VRE isolates were recovered from 61 patients; 96% of the
      isolates were Enterococcus faecium. VRE tended to be isolated from clinical
      specimens from patients identified as VRE carriers by stool surveillance (P <
      .01). However, isolation of VRE from surveillance cultures preceded clinical
      isolation for only approximately 50% of the patients from whom a clinical VRE
      isolate was recovered. Mortality was greater (P < .05) among patients from whom a
      clinical VRE isolate was recovered than among patients from whom VRE was isolated
      only by stool surveillance. The mortality (1[17%] of 6) among patients for whom
      VRE was isolated from blood was similar to that (10 [27%] of 37) among patients
      for whom vancomycin-susceptible enterococcus was isolated from blood (P = .97).
      Despite prompt initiation of contact precautions for VRE carriers, the incidence
      of fecal carriage of VRE remained approximately 8% among this patient population
      for the 6-month period of the study.

PMID- 7578760
TI  - Massive outbreak of waterborne cryptosporidium infection in Milwaukee, Wisconsin:
      recurrence of illness and risk of secondary transmission.
AB  - Contamination of the public water supply in Milwaukee during March and April 1993
      resulted in a massive outbreak of cryptosporidium infection. We investigated the
      clinical and epidemiological features of visitors to the Milwaukee area in whom
      cryptosporidiosis developed, and we conducted a telephone survey of Milwaukee
      County households to evaluate the risk of recurrent illness and secondary
      transmission. Cryptosporidium infection during this outbreak generally seemed
      more severe than cases described in previous reports of large case series. The
      risk of secondary transmission within a household was low (5%) when the index
      case involved an adult. The recurrence of watery diarrhea after apparent recovery
      was a frequent occurrence among visitors with laboratory-confirmed
      cryptosporidium infection (39%) and among visitors and Milwaukee County residents
      with clinical infection (21%). The interval between the initial recovery and the
      onset of recurrence was prolonged (> or = 5 days) in 6%-8% of persons. This
      pattern of recurrence and its impact on transmission and our understanding of the
      pathophysiological mechanisms of cryptosporidium infection merit further
      investigation.

PMID- 7578761
TI  - Waterborne cryptosporidiosis--setting the stage for control of an emerging
      pathogen.

PMID- 7578759
TI  - Cervical necrotizing fasciitis: clinical manifestations and management.
AB  - Forty-five cases of cervical necrotizing fasciitis are reported, and their
      clinical, bacteriologic, and therapeutic implications are considered. Fasciitis
      was of dental origin in 78% of cases, pharyngeal in 16%, and surgical or
      posttraumatic in 6%. The condition extended to the face in 22% of cases, to the
      lower part of the neck in 56%, and to the mediastinum in 40%. Soft-tissue
      cultures were positive in 78% of cases. Anaerobes were isolated along with
      aerobes in 49% of cases (mean, 2.2 isolates per patient) and in pure culture in
      22%. Treatment included surgical debridement and drainage and the administration
      of antibiotics active against both anaerobic and gram-negative aerobic bacteria.
      Hyperbaric oxygen was used for adjunctive treatment. The bacteria involved did
      not affect clinical manifestations, extension, or mortality. The survival rate
      among our patients was 78%. Mortality was significantly higher among cases with
      mediastinal extension (44% vs. 7%; P < .01); thus the prompt recognition and
      drainage of sites of mediastinal extension are of critical importance. Other risk
      factors for death were an age of > 70 years, underlying diabetes, the development
      of septic shock within 24 hours after admission, and prolonged prothrombin time.

PMID- 7578762
TI  - Localized soft-tissue infections with Mycobacterium avium/Mycobacterium
      intracellulare complex in immunocompetent patients: granulomatous tenosynovitis
      of the hand or wrist.
AB  - In immunocompetent patients, Mycobacterium avium/Mycobacterium intracellulare
      complex (MAC) has been associated with pulmonary infection in adults, cervical
      lymphadenitis in children, and disseminated infection in children and adults. MAC
      rarely has been recognized as a cause of localized soft-tissue infection in
      immunocompetent hosts. Six cases of granulomatous tenosynovitis due to MAC are
      reported; five cases occurred after local surgical procedures, trauma, or
      corticosteroid injection. In four cases, cure was achieved with combined medical
      and surgical intervention. In these six cases and 11 previously reported cases,
      both males and females were affected equally, usually in the fifth to seventh
      decades of life, and the distal upper extremity was predominantly involved.
      Surgical debridement with appropriate culture was critical for diagnosis and
      management. Antimycobacterial chemotherapy seemed to be a beneficial adjunctive
      measure in most cases but was clearly necessary for cure in only a few cases.

PMID- 7578763
TI  - Disseminated microsporidiosis due to Septata intestinalis in nine patients
      infected with the human immunodeficiency virus: response to therapy with
      albendazole.
AB  - Disseminated microsporidiosis due to the newly described species Septata
      intestinalis in nine patients infected with human immunodeficiency virus is
      described. All patients were male homosexuals; the mean age was 41 years (range,
      35-58 years). They were all severely immunocompromised, with a mean CD4
      lymphocyte count of 15/mm3 (range, 0-32/mm3). Infection by S. intestinalis was
      seen in duodenal biopsy specimens from all patients, and dissemination was
      demonstrated by the presence of microsporidial spores in urine (9 of 9 patients),
      sinonasal secretions and/or nasal mucosal biopsy specimens (6 of 6), and sputum
      (6 of 6). Seven patients were treated with albendazole (400 mg twice daily),
      resulting in significant dissipation or complete resolution of diarrhea for six
      patients and abatement of symptoms for the six patients with chronic
      rhinosinusitis. There was a parallel parasitological response, with clearance of
      S. intestinalis infection from almost all sites.

PMID- 7578764
TI  - Clinical manifestations and implications of coinfection with Mycobacterium
      kansasii and human immunodeficiency virus type 1.
AB  - We conducted a retrospective study to further elucidate the clinical
      presentations and prognosis of disease due to Mycobacterium kansasii in patients
      infected with human immunodeficiency virus (HIV). Forty-nine HIV-infected
      patients first had M. kansasii isolated at a mean CD4 cell count of 62/mm3 and at
      a mean interval of 17 months after the diagnosis of AIDS. Seventeen of the 49
      patients had disseminated disease caused by M. kansasii. Twenty-nine patients had
      a positive acid-fast smear of sputum, and 35 were known to be cigarette smokers.
      At the time of initial isolation of M. kansasii, 13 patients had other concurrent
      pulmonary isolates and 15 had another mycobacterial species concurrently isolated
      (the Mycobacterium avium complex in 13 instances). Patients who received
      antimycobacterial treatment survived longer than those who did not. Only one of
      the 49 patients was definitively determined to be colonized with M. kansasii
      without disease; therefore, it appears that pulmonary isolates of M. kansasii in
      HIV-infected patients are almost always associated with disease. The increase in
      rates of M. kansasii disease among HIV-infected patients has paralleled the rise
      of AIDS in Louisiana. So far, this state has recorded more coinfections with M.
      kansasii and HIV than any other.

PMID- 7578765
TI  - A multicenter comparative study of meropenem and imipenem/cilastatin in the
      treatment of complicated urinary tract infections in hospitalized patients.
AB  - The safety and efficacy of meropenem and imipenem/cilastatin were compared in the
      treatment of hospitalized patients with complicated urinary tract infections
      (UTIs) in a prospective, multicenter, open, parallel-group trial. Patients were
      randomized to receive 500-mg intravenous doses of either meropenem every 8 hours
      (n = 116) or imipenem/cilastatin every 6 hours (n = 119). Data from 95 patients
      given meropenem and 82 patients given imipenem/cilastatin were included in the
      evaluation of efficacy. Meropenem produced satisfactory clinical and
      bacteriologic responses in 99% and 90% of cases, respectively. These results were
      similar to those obtained with imipenem/cilastatin, which produced clinical
      improvement in 99% of cases and bacteriologic improvement in 81%. Two patients
      given meropenem and five patients given imipenem/cilastatin developed
      superinfections. The rate of relapse was similar in the two groups. Patients who
      received meropenem had fewer drug-related adverse reactions than did recipients
      of imipenem/cilastatin (8% vs. 19%). The results of this study demonstrate that
      meropenem is a safe and effective alternative to imipenem/cilastatin in the
      treatment of hospitalized patients with complicated UTIs.

PMID- 7578766
TI  - Invasive staphylococcal infections complicating percutaneous transluminal
      coronary angioplasty: three cases and review.
AB  - Infectious complications infrequently occur after percutaneous transluminal
      coronary angioplasty (PTCA) is performed. We recently treated three patients with
      invasive staphylococcal infections that developed after PTCA. Two patients had
      septic arthritis of the knee joint secondary to probable femoral endarteritis,
      and the third patient had an infected hematoma of the groin. Early reuse of the
      initial puncture site, prolonged retention of the femoral sheath, bleeding or
      hematoma at the femoral sheath insertion site and vascular complications such as
      pseudoaneurysm may predispose to infectious sequelae after PTCA. The clinician
      should be aware of these risks and the possibility that a patient may develop
      these potentially serious complications after PTCA.

PMID- 7578769
TI  - Mechanical behaviour of composite artificial tendons and ligaments.
AB  - The mechanical behaviour of a soft composite material based on a hydrogel polymer
      matrix reinforced with bundles of poly(ethylene terephthalate) (PET) fibres is
      analysed. The composite reproduces the typical J-shaped stress-strain curves
      displayed by natural tendons and ligaments. The lamination composite theory was
      used to investigate the role of the fibres and the matrix properties, as well as
      the role of the winding angle and the volumetric fraction of fibres, on the
      mechanical response of this system. The results suggested that large variations
      in the mechanical behaviour can be obtained by changing the winding angle of the
      fibres in the composite which determines the extent of the 'toe' region and the
      sensitivity of the system to the rigidity of the fibres.

PMID- 7578768
TI  - Temperature-modulated platelet and lymphocyte interactions with poly(N
      isopropylacrylamide)-grafted surfaces.
AB  - Temperature-responsive semitelechelic poly(N-isopropylacrylamide) (PIPAAm)
      bearing a carboxyl end group has been chemically immobilized on aminated
      polystyrene particle surfaces via condensation reaction. PIPAAm-grafted particles
      were uniformly suspended in aqueous media at lower temperatures. With increasing
      temperature, PIPAAm-grafted particles aggregated and precipitated. Such
      reversible changes in particle colloidal behaviour was correlated to temperature
      modulated hydrophilic/hydrophobic changes of particle surfaces modified by PIPAAm
      hydration/dehydration with temperature changes. Interactions between platelets
      and PIPAAm-grafted surfaces were studied by monitoring cytoplasmic free Ca2+
      concentration ([Ca2+]i) changes in platelets using intracellularly-trapped Ca2+
      indicator dye, Fura 2, at various temperatures. Although changes in [Ca2+]i in
      platelets in contact with PIPAAm-grafted particles were not observed below the
      critical temperature of PIPAAm, significant changes in [Ca2+]i in platelets were
      induced by contact with particles above this critical temperature. Furthermore,
      temperature-modulated cell adsorption/desorption control by PIPAAm-grafted
      particles was investigated using a particle aggregation assay in the presence of
      lymphocytes. Below the critical temperature of PIPAAm, mixed suspensions were
      completely homogeneous due to minimal interaction between lymphocytes and
      hydrated particles. In contrast, aggregated precipitates were observed by
      increasing the suspension temperature above the critical temperature of PIPAAm
      resulting from strong hydrophobic interactions between particles with
      lymphocytes. These precipitates are reversibly resuspended in cold buffer. The
      feasibility of cell activation/inactivation or cell attachment/detachment control
      by temperature-modulated surface changes is attractive for suspension cell
      culture and drug delivery at targeted sites in vivo.

PMID- 7578767
TI  - Is Blastocystis hominis a cause of diarrhea in travelers? A prospective
      controlled study in Nepal.
AB  - Although the pathogenicity of Blastocystis hominis has been extensively debated
      in the medical literature, controlled studies of the association between B.
      hominis and diarrhea are lacking. We conducted a case-control study among
      expatriates and tourists in Kathmandu, Nepal, in which we compared the prevalence
      of the organism among patients with diarrhea to that among a control group
      without diarrhea. B. hominis was detected in 56 (30%) of 189 patients with
      diarrhea, compared with 40 (36%) of 112 asymptomatic controls. Patients with
      diarrhea were significantly more likely to have > or = 10 B. hominis organisms
      per high-power (400x) field than were controls. However, among the 25 patients
      with this concentration of organisms, other enteric pathogens were detected in 17
      (68%). Only 8 (4%) of 189 patients with diarrhea had > or = 10 B. hominis
      organisms per high-power field detected in the absence of other pathogens,
      compared with 5 (5%) of 112 asymptomatic controls. Thus, B. hominis in higher
      concentrations was not associated with diarrhea. There were no specific symptoms
      associated with B. hominis infection, and the presence of higher concentrations
      of the organism in stool was not associated with more-severe symptoms. Despite
      the high prevalence of the organism among travelers and expatriates in Nepal, the
      results of this study suggest that B. hominis does not cause diarrhea in this
      population.

PMID- 7578770
TI  - Seven surgical silicones retain Staphylococcus aureus differently in vitro.
AB  - In an in vitro study, we have quantitatively evaluated the capability of seven
      different types of silicone to retain a Staphylococcus aureus strain, isolated
      from a surgical wound. All the silicone specimens were taken from prostheses
      already used in plastic or ophthalmological surgery. Two polymers were used as
      controls: polystyrene, because of its known capability to favour in vitro
      bacterial recovery, and nylon, for its bacterial repellence. The results show
      that all silicones are suitable substrata for Staphylococcus aureus. However,
      there are some differences among silicone types. The amounts of bacteria retained
      from silicone oils are greater than or equal to those obtained from the positive
      control material.

PMID- 7578771
TI  - Disposable contact lenses and bacterial adhesion. In vitro comparison between
      ionic/high-water-content and non-ionic/low-water-content lenses.
AB  - An in vitro quantitative study of the adhesion of a Staphylococcus aureus strain
      to two types of disposable contact lenses has been carried out. The first type
      was an ionic/high-water-content (I-HWC) lens (42% Etafilcon A, 58% water) and the
      second was a non-ionic/low-water-content (Nl-LWC) lens (61.4% poly(2-hydroxyethyl
      methacrylate), 38.6% water). Adhesion to the two lens types was evaluated both in
      basic conditions and after treatment with lysozyme. The results showed that I-HWC
      lenses are more prone to Staphylococcus aureus adhesion than NI-LWC lenses, both
      untreated (+15.4%) and treated with lysozyme (+20.5%). Lysozyme increased
      bacterial adhesion by 30.5% on the lenses with lower water content, and by 36.3%
      on those with higher water content.

PMID- 7578773
TI  - Adsorption of bovine serum albumin onto hydroxyapatite.
AB  - The adsorption of bovine serum albumin (BSA) onto hydroxyapatite (HA) has been
      studied as a function of protein concentration, pH and ionic strength. Isotherm
      data (adsorption being a reversible process) have been analysed using the
      Langmuir model, the adsorption parameters AT (maximum amount of protein adsorbed,
      mg m-2) and K (affinity constant, L g-1) being calculated for each solution
      condition (except NaF). For the pH dependence of adsorption, both AT and K
      increase with decreasing pH, indicating that both electrostatic and hydration
      effects are important. For the ionic strength dependence, increasing NaCI
      concentrations result in a slight increase in AT, but K decreases. With
      increasing CaCI2 concentrations the AT and K values increase, the opposite being
      true for increasing concentrations of Na2HPO4. NaF both enhances and inhibits
      adsorption depending on the concentration. Possible reasons for these results are
      discussed.

PMID- 7578772
TI  - Crystallite orientation and anisotropic strains in thermally sprayed
      hydroxyapatite coatings.
AB  - Thermally sprayed hydroxyapatite powders and coatings have been studied using X
      ray powder diffraction and scanning electron microscopy. Preferred orientation of
      the crystallites has been found on a number of coated plates using X-ray powder
      diffraction, and full profile fitting of the patterns from the extracted powders
      indicates anisotropically thermally strained crystallites. This is a result of
      rapid crystal regrowth and associated thermal gradients on deposition. Electron
      micrographs of some coatings show a consistent picture of columnar crystallites
      orientated perpendicular to the substrate surface.

PMID- 7578774
TI  - Crystallographic properties of heterogeneous Mg-containing fluoridated apatites
      synthesized with a two-step supply system.
AB  - Mg-containing fluoridated hydroxyapatites (Mg-MgFAp and MgF-MgAp) were
      synthesized heterogeneously with two different modes of fluoride supply. The
      expanded (300) reflections of the X-ray diffraction of both apatites were broader
      than and different from those of the mechanical mixture of the homogeneous
      apatites (MgAp and MgFAp). Scanning electron microscopy (SEM) showed that the
      crystal size and shape of Mg-MgFAp and MgF-MgAp were different. Energy dispersive
      spectroscopy (EDS) indicated that the fluoride intensity of Mg-MgFAp synthesized
      with the fluoride supply in the latter half of the experimental period was higher
      than that of MgF-MgAp. The apparent solubility of Mg-MgFAp was lower than that of
      MgF-MgAp. These results suggested that two different types of Mg-containing
      fluoridated hydroxyapatites might be formed: surface fluoride-rich apatites (Mg
      MgFAp) and inner fluoride-rich apatites (MgF-MgAp).

PMID- 7578775
TI  - Development of calcium phosphate based functional gradient bioceramics.
AB  - A functional gradient bioceramic that can function gradually with respect to body
      tissue was studied by changing the composition of calcium phosphate gradually
      from the surface to the inside. Diamond powder was spread on the surface of
      compact hydroxyapatite (HA) powder and fired at 1280 degrees C under reduced
      pressure, followed by firing under atmospheric conditions. The sintered body thus
      prepared was dense and alpha-tricalcium phosphate (alpha-TCP: alpha-Ca3(PO4)2)
      was found on its surface. The content of alpha-TCP gradually decreased with
      increasing depth from the surface. In contrast, the content of HA increased with
      increasing depth from the surface. The gradient ratio of alpha-TCP and HA depends
      on the firing time for each condition, i.e. reduced or atmospheric pressure. The
      alpha-TCP formation was ascribed to the decomposition of HA due to the
      spontaneous combustion of diamond powder.

PMID- 7578776
TI  - Effect of sintering temperature on silica gels and their bone bonding ability.
AB  - Silica gels gave rise to apatite precipitation onto their surface depending on
      the sintering temperature. Silica gels prepared at different sintering
      temperatures were studied in vivo in cortical bone for their bone bonding ability
      in relation to their apatite precipitation. From the results we conclude that the
      sintering temperature influenced the stability of the material. Sintering at the
      lower temperatures of 400 and 600 degrees C allow the silica gels to be degraded
      more easily, while gels treated at 900 and 1000 degrees C were more stable. The
      more stable gels showed some bone bonding, while the degraded gels evoked a high
      cellular reaction of giant cells and lymphocytes.

PMID- 7578777
TI  - Corrosion of intra-oral magnets in the presence and absence of biofilms of
      Streptococcus sanguis.
AB  - Intra-oral magnets are used in dentistry for a variety of purposes, and their
      susceptibility to corrosion is of great clinical importance. Although a number of
      in vitro models have been developed to study corrosion of intra-oral magnets,
      none have attempted to determine the possible contribution to corrosion made by
      oral bacteria, which are known to form a biofilm on intra-oral appliances. We
      have exposed demagnetized neodymium/iron/boron (Nd2Fe14B) magnets to an
      artificial saliva in the presence and absence of a biofilm of Streptococcus
      sanguils, one of the predominant organisms in the oral cavity. Over a 21-d
      period, a 3.2% decrease in the mass of the magnets was observed when S. sanguis
      was present, while in the absence of the organism the decrease in mass was 1.4%.
      We also examined the ability of poly(para-xylylene), a commonly-used coating, to
      protect the magnets against corrosion. No decrease in the mass of magnets coated
      with poly(para-xylylene) was detected over a 21-d period in the presence of S.
      sanguis. This study has shown that biofilms of S. sanguis cause appreciable
      corrosion of Nd2Fe14B magnets which is greater than that occurring in the absence
      of the organism, and that a coating of poly(para-xylylene) provides protection
      against such corrosion.

PMID- 7578778
TI  - Effect of constant and modulated electrical charges applied to the culture
      material on PGI2 and TXA2 secretion by endothelial cells.
AB  - Electrical stimulation of an endothelial cell culture applied through the culture
      support biomaterial induced strong secretion of prostaglandin I2 (PGI2) and, to a
      lesser extent, thromboxane A2 (TXA2), which varied with time, the sign of the
      stationary electrical charge and the amplitude and frequency of a superimposed
      sine wave. In stationary conditions, the response is more rapid at positive
      electrical charges (+ some tens of microC cm-2) than at negative ones (-some tens
      of microC cm-2). In sine wave conditions, the ratio [PGI2]/[TXA2] is strongly
      increased and is maximum for an amplitude of 50 mV and a frequency of 1 Hz. These
      results suggest that the extracellular matrix is not only involved in cellular
      anchoring but also participates actively in secretion of thrombomodulatory
      substances, an effect apparently related to the piezoelectric properties of its
      components.

PMID- 7578779
TI  - Electrochemical impedance spectroscopy of preoxidized MA 956 superalloy during in
      vitro experiments.
AB  - Preoxidation treatment of MA 956 superalloy at 1100 degrees C produces a fine and
      tightly adherent alpha-alumina layer at the surface, which provides the alloy
      with an excellent barrier against a great variety of aggressive environments. In
      this work the protective capacity of the alumina/alloy system is evaluated in a
      physiological medium by means of electrochemical impedance spectroscopy. The
      electrochemical response of the material is modelled by equivalent circuits which
      provide the most relevant corrosion and protection parameters applicable to MA
      956 in both preoxidized and as-received conditions (passivated state). The high
      protective capacity of preoxidized MA 956 superalloy holds for long-term tests,
      which indicates that the corrosion phenomena, if any, would be characterized by
      very slow kinetics. The corrosion resistance of the preoxidized material is at
      least two orders of magnitude higher than that of the non-treated alloy.

PMID- 7578780
TI  - X-ray microanalytical and morphological observations of the interface region
      between ceramic implant and bone.
AB  - In 8 monkeys both the maxillary lateral incisors were extracted. In the 16
      extraction sites an Al2O3-ceramic dental implant (Frialit) was immediately
      inserted. Eight implants were submerged under the oral mucosa and the other 8
      were allowed to penetrate through the mucosa during the observation period. None
      of the implants was loaded during the observation periods. After experimental
      periods of 1, 2, 4 and 8 months, the interface region between the implant and
      bone was examined using scanning-electron microscopy, X-ray microanalysis, back
      scatter, microradiography and light microscopy. The results showed that
      osseointegration of Al2O3-ceramic dental implant was obtained. The newly formed
      bone around the implant filled exactly the contours of the implant. Newly formed
      bone had a mineral content and a phosphorus-to-calcium ratio similar to that of
      the adjacent older mature jaw bone. There were no differences in the
      osseointegration rate between the submerged and the nonsubmerged implants. No
      leakage of aluminium from the implant could be detected in the bone.

PMID- 7578782
TI  - Osseointegration of Branemark fixtures using a single-step operating technique. A
      preliminary prospective one-year study in the edentulous mandible.
AB  - The aim of the present prospective clinical study was to analyze the feasibility
      of inserting Branemark fixtures according to a one-stage procedure including
      transmucosal healing and to subsequently evaluate the predictability of
      osseointegration as well as the potential of such implants for stabilizing
      complete overdentures in the edentulous mandible. Five patients (2 women, 3 men),
      completely edentulous in the mandible and with a mean age of 60 years,
      volunteered for this study. Two fixtures of various length (10-20 mm) and 3.75 mm
      in diameter were inserted in the lower canine regions. A standard surgical
      procedure including a midcrestal incision was used. After the placement of the
      fixtures, healing abutments, which are normally used during second-stage surgery,
      were inserted instead of the usual cover screws. Three months after implant
      placement a clinical and radiographic examination was performed to confirm the
      presence or absence of osseointegration of the fixtures prior to exchanging the
      healing abutments with the spherical attachments. Finally, different clinical
      (Plaque Index, Bleeding Index, probing depth, Periotest mobility) and
      radiographic (bone loss, peri-implant radiolucency) parameters were recorded 9
      months after loading of the fixtures by means of a complete mandibular
      overdenture, retained by two ball attachments in the canine regions. All fixtures
      were perfectly stable (mean Periotest values of -2) and presented favorable peri
      mplant soft tissue conditions, and no patient was complaining about any
      particular symptom. As far as retention and stability of their implant supported
      overdenture was concerned, the participants without exception considered the
      therapeutic result as being perfectly adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578781
TI  - Bridges supported by free-standing implants versus bridges supported by tooth and
      implant. A five-year prospective study.
AB  - The clinical question at issue, whether it is possible to combine implants and
      natural teeth via fixed bridges, is of current interest. The treatment of the
      subjects of this prospective study was performed between June 1984 and December
      1986. This article presents the 5-year results of the study. The consecutive
      patient material comprised 23 patients with Applegate Kennedy Class I residual
      dentition in the mandible and a complete maxillary denture. All 23 patients were
      provided with implants ad modum Branemark in each mandibular quadrant. One side
      was randomized to rehabilitation with fixed bridge between the distal tooth of
      the residual dentition and an implant; the other side received a free-standang
      bridge on 2 implants. The fixture survival rate was 88%. No difference was found
      between the two sides. Bridge stability was 89% for the implant bridges and 91%
      for the combination bridges. The change in marginal bone level at the implants
      was small during the 5-year follow up period (on average 0.1-0.3 mm) and with no
      difference between the two sides. In conclusion, it was not possible to
      demonstrate any higher risk of implant or prosthetic failure for tooth-implant
      fixed bridges compared with implant-supported bridges.

PMID- 7578783
TI  - Augmentation of intramembraneous bone beyond the skeletal envelope using an
      occlusive titanium barrier. An experimental study in the rabbit.
AB  - The aim of this investigation was to evaluate whether augmentation of
      intramembraneous bone beyond the skeletal envelope can be predictably achieved by
      placing a completely occlusive barrier on the skull bone of rabbits, hereby
      creating a secluded space with bone tissue being the only adjoining tissue. The
      experiment was carried out in 3 New Zealand white rabbits. In each animal, a
      midline incision was made down to the bone surface of the skull and a skin
      periosteal flap was raised to expose the skull bone on both sides of the midline.
      Two prefabricated titanium domes with an inner diameter of 4.5 mm and an inner
      height of 3.0 mm were installed on each side. The domes were supplied with a
      horizontal, peripheral flange and a vertical edge, fitting tightly into a
      circular slit, prepared by a trephine into the skull bone. This arrangement
      ensured a stable anchorage of the dome and a reliable peripheral sealing of the
      space. The skin-periosteal flaps were relocated to cover the domes and sutured.
      After a healing period of 3 months, the animals were killed and the experimental
      areas excised and prepared for histological transversal ground sections with each
      dome in situ. The results demonstrated complete bone fill of all domes, with no
      signs of ingrowth of other types of tissues, indicating that the use of a barrier
      with total occlusiveness, sufficient stiffness and stability and reliable
      peripheral sealing will result in predictable bone augmentation of spaces also
      beyond the skeletal envelope.

PMID- 7578785
TI  - Threshold of tactile sensitivity perceived with dental endosseous implants and
      natural teeth.
AB  - The aim of this study was to determine the threshold of tactile perception of
      endosseous dental implants and to assess the relative difference of that
      threshold between implants and teeth. Twenty-two subjects with implants of the
      ITI Dental Implant System were included in the study. All implants served as
      abutments for single tooth crowns and had been in function for a minimum of 1
      year. A strain gauge glued to the shaft of an amalgam plugger served as a force
      sensor. It transformed the elastic deformation exerted onto the shaft into an
      electronic signal for recording. By use of the amalgam plugger, a continuously
      increasing force was exercised on the implants or teeth until the first sensation
      of touch was indicated by the patient. Statistical analysis revealed threshold
      values for the implants ranging from 13.2 to 189.4 g (1 g = 0.01 N) (mean 100.6;
      SD 47.7), while a range of 1.2 to 26.2 g (mean 11.5; SD 11.5) was found for
      control teeth. Thus, the mean threshold values for implants were 8.75 times
      higher than for teeth. This difference was highly statistically significant. A
      general linear models procedure was applied to determine the influence of patient
      age, jaw, implant position and the threshold values of teeth on the measurements
      obtained for implants. Only gender and the threshold values for contralateral
      teeth had a significant influence. These 2 parameters together explained 27% of
      the variability in threshold measurements. It is concluded that a more than 8
      fold higher threshold value for tactile perception exists for implants compared
      with teeth.

PMID- 7578784
TI  - Periotest measurements and osseointegration of mandibular ITI implants supporting
      overdentures. A one-year longitudinal study.
AB  - The Periotest values of mandibular implants, registered before and after loading
      by overdentures, were compared. Thirty edentulous patients with 60 Bonefit ITI
      implants were selected with an average age of 69 years. The Periotest values were
      measured 1) after a healing period of 3 months and 2) after the overdentures had
      been worn for a period of 12 months. Periodontal parameters were recorded at both
      examinations. Furthermore, 17 biopsies of mandibular bone taken from the implant
      sites during implant surgery were analyzed to assess the bone density. The
      histomorphometric evaluation was done using a point count method. At the end of
      the healing period, all registered Periotest values were negative, ranging from 
      1 to -8 with an average of 4.08. One year later, all measurements showed negative
      values again, ranging from -2 to -8 with an average of 4.97. The difference was
      statistically significant. Seventeen biopsies of mandibular bone were evaluated
      to determine the density. The range of bone density was from 22.4% and 90.9%.
      There was no correlation found between bone density and Periotest values.
      However, a significant correlation could be observed between mandibular atrophy
      and bone density.

PMID- 7578786
TI  - A new method to obtain bone biopsies at implant sites peri-operatively: technique
      and bone structure.
AB  - This study aims at evaluating an objective method for the description of bone
      structure in the human mandible. Human bone biopsies were harvested at mandibular
      implant sites prior to insertion of self-tapping Mark II fixtures. Altogether 15
      biopsies were taken from 12 patients. Three patients donated 2 biopsies each, one
      proximally and one distally taken. Ground sections of about 100 microns thickness
      were prepared prior to microradiography. These sections were ground to a final
      thickness of about 10 microns followed by histological staining.
      Histomorphometrical analyses were performed on the microradiographed plates and
      on the ground sections. On average there was a bone area of about 54% calculated
      on the microradiographed plates (the 100-microns sections) versus a mean bone
      area of 62% light microscopically (the 10-microns sections). Bone lengths were
      calculated on the 10-microns sections in the central part (mid-line) and on each
      side of the mid-line, revealing a mean of 58% in the former case and a mean of
      61% in the latter case. The amount of bone varied between individuals and in
      different locations of the same jaw. The postoperative healing period following
      fixture installation is standardized regardless of bone structure. It may in the
      future be appropriate to more individualize this healing period based on an
      objective bone quality score.

PMID- 7578787
TI  - Measurements of distances related to the mandibular canal in radiographs.
AB  - Before implant surgery in the mandibular side segment, it is of utmost interest
      to locate the mandibular canal in radiographs to avoid interference with the
      neurovascular bundle during surgery. Six mandibular specimens were
      radiographically examined with 2 panoramic and 3 tomographic techniques. The
      distances between the superior border of the canal and the alveolar crest and
      between the mandibular base and the inferior border of the canal were measured.
      In addition, the height of the canal was measured. The measurements were
      performed by 3 or 4 observers and compared with measurements on contact
      radiographs of the same areas. Tomography gave more accurate values of the above
      distances than panoramic techniques. The variation between observers in detecting
      the mandibular canal was large.

PMID- 7578788
TI  - Plaque-induced peri-implantitis in the presence or absence of keratinized mucosa.
      An experimental study in monkeys.
AB  - In 5 monkeys a total of 30 transmucosal endosseous dental implants were inserted
      in edentulous areas of the mandible with presence or absence of keratinized
      mucosa. After a healing period of 3 months with optimal plaque control, all
      implants were exposed to plaque accumulation for periods up to 9 months. To
      secure abundant plaque accumulation on half the number of the implants, cotton
      wool ligatures were placed around the implants at the entrance to the peri
      implant sulcus. Attachment loss was measured clinically and histometrically, and
      tissue recession was measured clinically. Ligated implants without keratinized
      mucosa demonstrated significantly more recession and slightly more attachment
      loss than the other implants. The results of this study suggest that the absence
      of keratinized mucosa around dental endosseous implants increases the
      susceptibility of the peri-implant region to plaque-induced tissue destruction.

PMID- 7578789
TI  - Influence of the suprastructure on the peri-implant tissues in beagle dogs.
AB  - The purpose of this study was to compare clinical, radiographic and histological
      differences around titanium oral implants loaded with either acrylic-veneered
      metal or ceramo-metal fixed prostheses. Five beagle dogs were used in this
      investigation. At the beginning of the study, all mandibular premolars and first
      molars were extracted. After 3 months of healing, 2 Branemark implants were
      installed on each side of the mandibles. Three months later, abutments were
      inserted on each implant and a daily oral hygiene regime was initiated. One month
      after abutment connection, the implants on one side of the mandible were restored
      with an acrylic-veneered metal fixed prosthesis, whereas, on the other side a
      ceramo-metal fixed prosthesis was inserted. The prostheses were constructed in
      occlusion with the maxillary first molars. The following clinical parameters were
      measured around each implant at this time (i.e., baseline), and thereafter, at
      monthly intervals up to 5 months: Plaque Index; Gingival Index; implant mobility
      (using the Periotest); probing depth and clinical attachment level (using the
      Florida Probe). In addition, standardized radiographs were taken at baseline and
      5 months after insertion of the prostheses and evaluated by subtraction
      radiography. Another Branemark fixture was installed on each side of the
      mandibles 3 months before the end of the study. These implants remained unloaded
      and submerged for the entire study period. Five months after prosthesis
      insertion, the animals were killed, and implants with their supporting peri
      implant tissues were processed for histological evaluation. Analyses of the
      clinical, radiographic and histometric parameters revealed no significant
      differences between the acrylic-veneered and ceramometal loaded
      implants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578790
TI  - Osseointegration of subperiosteal implant via guided tissue regeneration. A pilot
      study.
AB  - The principle of guided tissue regeneration was applied in an attempt to generate
      bone to cover a subperiosteal implant. Titanium frame works, casted on individual
      impressions of the anterior surface of the tibia of 4 Copenhagen White rabbits,
      were stabilized to the tibia by microscrews, and half of them were covered by an
      expanded polytetrafluoroethylene augmentation membrane. The observation period
      was 12 weeks. Guided bone regeneration partly covering the implants was seen at
      all experimental sides; on the control sides the implants were mainly embedded in
      fibrous tissue. Studies are in progress with the aim of reducing marked marrow
      space formation observed in all the regenerated areas.

PMID- 7578791
TI  - Bone apposition onto oral implants in the sinus area filled with different
      grafting materials. A histological study in beagle dogs.
AB  - The placement of oral implants into jaw bone has a high predictability provided
      an adequate bone volume surrounding the implant is present to ensure primary
      stability and resistance to functional loading forces after completion of
      osseointegration. In the distal area of the maxilla, an adequate bone volume is
      often lacking because of the proximity of the sinus cavities. The aim of this
      study was to evaluate histologically the simultaneous placement of endosseous
      implants into the sinus cavity and the surgical elevation of the sinus floor
      including filling the cavity with different grafting materials. In 9 sinus areas
      of 5 beagle dogs, 9 titanium implants (ITI Dental Implant System) were placed,
      and the void space of the sinus cavity was filled simultaneously with either
      demineralized freeze-dried human cortical bone (Musculoskeletal Transplant
      Foundation), resorbable hydroxyapatite (Osteogen) or natural cancelleous bovine
      bone mineral (Bio-Oss). To study bone formation, fluorochrome markers
      (tetracycline HCl and calcein green) were used at 2 and 8 weeks. Clinically, all
      implants healed uneventfully, and 5 months after implant placement the dogs were
      killed for histologic evaluation. All implants exhibited osseointegration within
      the pre-existing cortical bone of the sinus floor. The implants surrounded by
      freeze-dried bone xenografts yielded no formation of new bone, whereas the sites
      with hydroxyapatite or natural bovine bone mineral demonstrated newly formed bone
      with direct contact at the implant surface. The average extent of bone to implant
      contact was 25% (SD = 10.6%) and 27% (SD = 8.8%), respectively in relation to the
      length of the originally denuded implant surface.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7578792
TI  - Evaluation of bone density using cutting resistance measurements and
      microradiography: an in vitro study in pig ribs.
AB  - A method using cutting resistance measurements during low-speed threading for
      identification of various bone densities has been evaluated with regard to its
      precision and potential. Pig ribs were used as test samples. Differing hand
      pressure, minor deviation (5 degrees) from a vertical tapping direction and
      individual threading did not reveal any significant differences in cutting
      resistance values. After implants were inserted into the threaded canals, the
      total bone as well as trabecular and compact bone areas surrounding the implants
      were calculated via a computer program and using microradiographs of the bone
      test samples. The outcome of the cutting resistance measurements was compared
      with that of the microradiographic technique, and good agreement was observed
      between the two procedures in the ability to identify bone density. Therefore,
      cutting resistance measurements may in the future also be used to clinically
      identify bone qualities in jaws.

PMID- 7578793
TI  - Accuracy of implant-supported prostheses in the edentulous jaw: analysis of
      precision of fit between cast gold-alloy frameworks and master casts by means of
      a three-dimensional photogrammetric technique.
AB  - Distortions of 15 routine implant-supported prostheses were measured in relation
      to the master casts after completion by means of a 3-dimensional (3-D)
      photogrammetric technique. All prostheses were designed as one-piece gold-alloy
      castings with resin teeth. Five of the prostheses were placed in the edentulous
      maxilla, and the remaining were placed in the lower jaw. Distortion of the
      cylinders was mostly observed in the horizontal plane (x- and y-axis) while the
      vertical aspect seemed to be more stable. The mean 3-D center point distortion
      was 42 (SD 15) and 74 (SD 38) microns for the upper and lower jaws, respectively.
      The measurements revealed a range of 3-D center point distortion from 16 to 80
      and 15 to 165 microns for the different jaws, respectively. The corresponding 3-D
      mean angular distortion of the cylinders was 51 (SD 35) microns in lower and 70
      (SD 75) microns in the upper jaws. A correlation was found between 3-D center
      point distortion and the width as well as the curvature of the implant arch,
      indicating more displacement the wider and the more curved the arch was. The 3-D
      center point distortion was also significantly higher in the upper jaws which
      could possibly be explained by the curvature of the implant arch and higher
      numbers of implants in the upper jaws. Further problems with the fit of upper jaw
      castings could be related to more alloy in the castings and poor alignment of
      implants.

PMID- 7578794
TI  - Mandibular single crystal sapphire implants: changes in crestal bone levels over
      three years.
AB  - A total of 190 single crystal sapphire implants, 85 short (4S9S) and 105 long
      (4S9L), were monitored with panoramic and intraoral radiographs for 3 years. The
      implants were used as abutments for overdentures in edentulous mandibles in 51
      patients. Within the first year, 2 patients lost one implant each due to pain and
      lack of osseointegration. Neither was replaced and the superstructures remained
      stable. At baseline registration, i.e., immediately after the prosthetic
      installation, the bone height relative to the length of the implant was
      calculated. The mean bone implant score (BIS) was 63.55 +/- 1.34% (mean +/- SE).
      BIS decreased during the first year 62.18 +/- 1.51%. At the 2- and 3-year
      recordings, the mean BIS were 61.81 +/- 1.58% and 61.73 +/- 1.63%, respectively.
      There were no statistically significant differences in BIS changes over the 3
      year period or between men and women. The decrease in mean BIS was greater for
      implants in the premolar region than in the incisor region and for short implants
      than for long implants.

PMID- 7578795
TI  - Clinical evaluation of guided bone regeneration at exposed parts of Branemark
      dental implants with and without bone allograft.
AB  - This investigation evaluated guided bone regeneration with a
      polytetrafluoroethylene barrier membrane at exposed parts of Branemark dental
      implants with and without concomitant use of decalcified freeze-dried bone
      allograft. Density of the regenerated tissue was also determined using a No. 23
      probe at a pressure of 25 g and was graded from 1 to 5. The higher index was
      associated with a higher resistance of newly formed tissue to the pressure of the
      probe. In 19 patients, 23 defects were treated by barrier membrane alone and 11
      defects by bone allograft with barrier membrane. The width and the depth of the
      defects were determined at the time of the implant placement and at the second
      stage implant surgery. When success was defined as 0 mm of residual defect, the
      mean success rate was 68% for the membrane group and 90% for the membrane group
      with bone allograft, with no statistically significant difference between the two
      treatment groups. The two groups did not demonstrate a significant difference in
      median density index. There was a significant positive relationship between time
      of membrane coverage and density index. A density index of 4 was only recorded
      after 7 months of membrane coverage. The present findings suggest beneficial
      clinical effect with the use of membrane alone and freeze-dried bone allograft
      with membrane for guided bone regeneration. This study proposed the use of a
      novel density index for clinical evaluation of regenerated tissue.

PMID- 7578796
TI  - Mechanotransduction by vascular smooth muscle.
AB  - Mechanotransduction by vascular smooth muscle (VSM) is defined as a cellular
      response (contraction, secretion, growth, division) to transmural pressure or
      stretch. This review includes an overview of the physical forces VSM cells
      experience in vivo, consideration of experimental techniques used to study VSM
      mechanotransduction, and a discussion of the scientific literature pertinent to
      the individual cellular components that have been implicated in the transduction
      of physical forces. These include: the extracellular matrix, integrins, ion
      channels, the sarcoplasmic reticulum, second messenger systems, contractile
      proteins, and the cytoskeleton.

PMID- 7578798
TI  - Three-dimensional collagen organization of human brain arteries at different
      transmural pressures.
AB  - Measurements on the directional organization of collagen are necessary for
      relating the structure and mechanical function of blood vessels. The birefringent
      optical property of collagen has enabled us to assess the collagen architecture
      for brain arteries, which are prone to spasm and aneurysm formation. Using the
      universal stage and polarizing microscope, we measured the three-dimensional
      organization of the collagen of the main layers of the artery wall, and examined
      the effect of distending pressure on that organization. Adult arteries obtained
      from autopsy were fixed at one of three distending pressures, 30, 120 and 200 mm
      Hg; they were embedded in paraffin and sectioned parallel to the vessel axis at 4
      microns thickness. Sections were stained with picrosirius red, a birefringent
      enhancement stain specific for collagen. Orientation data were obtained from
      tangential sections from thirteen arteries. We chose to use tangential sections
      that graze the curving surface of individual layers, to permit measurements that
      are equally sensitive to fibres in the mechanically meaningful range of
      directions including longitudinal, helical and circumferential. Each measurement
      was from a single fibre or group of fibres at a specific location; the mean
      direction and its variation of alignment within each artery layer were
      calculated. In some arteries, the adventitia and subendothelium measurements were
      separated into sublayers, distinguishable by the birefringent optical appearance.
      Main findings included a substantial component of longitudinal fibres in the
      adventitia and subendothelium, highly varied in coherence and mean direction, and
      a thin collagen layer of the adventitia, radially outside the medial muscle
      cells, that was highly organized circumferentially (circular standard deviation
      of 9 degrees). At higher pressures, the collagen fabric of all the layers was
      increasingly coherent and more circumferential in direction.

PMID- 7578799
TI  - Decreased PO2 and rabbit aortic smooth muscle mechanics.
AB  - Rabbit thoracic aorta was used to determine the effects of decreasing PO2 on the
      mechanical properties of contractions in response to norepinephrine (NE) and KCl.
      Aortae were aerated with 45% O2/5% CO2/50% N2 and stimulated with 10 microM NE or
      50 mM KCl. At 5 min of stimulation, 5% CO2/95% N2 aeration was introduced for 15
      min, defined as hypoxia. This time period was previously shown to produce similar
      decrease in [ATP] in either stimulation condition. Force, stiffness and isotonic
      shortening velocity were monitored during the initial stimulation, during hypoxia
      and during re-oxygenation. Hypoxia produced a substantial and rapid decrease in
      force and a concomitant decrease in stiffness during NE stimulation; delayed and
      smaller decreases in force and stiffness were observed during KCl stimulation.
      The force-stiffness relationship was steeper during KCl than NE stimulation, and
      hypoxia did not affect these relationships. Isotonic shortening velocity was
      significantly depressed by hypoxia during both stimulations although the decrease
      during KCl stimulation required a longer time. These data demonstrate that
      relaxation of an agonist-induced contraction in response to hypoxia results from
      a decrease in the number of activated crossbridges and not formation of rigor
      bridges.

PMID- 7578797
TI  - Vascular smooth muscle glycogen metabolism studied by 13C-NMR.
AB  - Vascular smooth muscle glycogen stores are traditionally thought to be small
      compared to other glycogen-containing tissues such as striated muscle or liver.
      However, glycogen has been thought to be an important carbon substrate for
      oxidative metabolism in support of contraction in vascular smooth muscle. We
      examined the synthesis and degradation of glycogen in isometrically mounted hog
      carotid artery using 13C-NMR spectroscopy. The rate of net glycogen synthesis
      from 1-13C-glucose was found to be constant during the first 8 h of incubation of
      carotid arteries with 10 mM glucose at 37 degrees C and then decreased towards a
      rate of zero by 14 h of incubation. During 8 h of incubation in the presence of 5
      mM glucose, the content of glycogen increased from 1.5 to 8.1 mumol/g blot weight
      in the absence of insulin and to 11.4 mumol/g blot weight in the presence of 0.5
      U/ml insulin. During prolonged glycogen loading, there was a simultaneous
      degradation of previously synthesized 6-13C-glycogen during synthesis of 1-13C
      glycogen from 1-13C-glucose indicating substrate cycling of glycogen metabolism.
      This substrate cycling results in a pattern of glycogen utilization in which the
      most recently synthesized glucosyl units of glycogen are utilized only slightly
      more readily than the previously synthesized glucosyl units of glycogen. We
      conclude that glycogen stores are larger and more dynamic than previously thought
      in vascular smooth muscle consistent with an important role for glycogen as a
      carbon source for smooth muscle energy metabolism.

PMID- 7578800
TI  - Long-term sensory denervation does not modify endothelial function or endothelial
      substance P and nitric oxide synthase in rat mesenteric arteries.
AB  - Mesenteric endothelial cell function and immunoreactivity for substance P and
      nitric oxide synthase (NOS) were examined in control rats and rats treated with
      capsaicin as neonates to destroy primary afferent nerves. Endothelial vasodilator
      function was examined pharmacologically in the methoxamine raised-tone isolated
      perfused mesenteric arterial bed. Endothelial immunoreactivity for substance P
      and NOS was examined at the ultrastructural level by electron-microscopic
      immunocytochemistry. The endothelium-dependent vasodilators acetylcholine and
      adenosine 5'-triphosphate elicited dose-dependent relaxations which were not
      different between control and capsaicin-treated rats. Dose-dependent relaxations
      to endothelium-independent vasodilators, calcitonin gene-related peptide and
      sodium nitroprusside, were also unchanged by capsaicin treatment. Positive
      staining for substance P was detected in 25% of endothelial cells in both control
      and capsaicin-treated rats. Positive staining for NOS was detected in 50% of
      endothelial cells in control rats, and this was not changed by capsaicin
      treatment. These results confirm that endothelial substance P is independent of
      substance P contained in sensory nerves. Long-term sensory denervation does not
      produce changes in endothelium-dependent or -independent relaxation, or in the
      number of endothelial cells showing positive labelling for substance P and NOS in
      rat mesenteric arteries.

PMID- 7578801
TI  - Low- and high-density lipoproteins as mitogenic factors for vascular smooth
      muscle cells: individual, additive and synergistic effects.
AB  - The mitogenic activities of low (LDL)- and high (HDL)-density lipoproteins have
      been examined in cultures of human vascular smooth muscle cells (VSMC). LDL and
      HDL3 dose-dependently (EC50 values approximately 50 micrograms/ml) stimulated DNA
      and protein synthesis ([3H]-thymidine and [3H]-leucine incorporation,
      respectively) in the absence of exogenously added mitogens. The synthetic
      responses of VSMC to combinations of LDL and HDL3 were additive, indicating that
      each lipoprotein mediates discrete effects. LDL or HDL3 promoted VSMC
      proliferation under strict mitogen-free conditions, but this growth response was
      not sustained. VSMC exposed to combinations of lipoproteins (either LDL or HDL3)
      and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited synergistic DNA
      synthesis responses. In the combined presence of PDGF-BB and either LDL or HDL3,
      VSMC proliferation was sustained. Anionized lipoprotein preparations (oxidized,
      acetylated, carbamylated or malonimylated) also stimulated DNA and protein
      synthesis. Since the antioxidant beta-hydroxylated toluene did not block the
      effect of native LDL on DNA synthesis, and fucoidin, a specific competitor for
      the 'scavenger' receptor, did not inhibit oxidized LDL-induced DNA synthesis,
      activation of mitogenic signals by lipoproteins does not depend on lipid
      peroxidation. Rather, the apparent intrinsic mitogenic potential of lipoproteins
      may depend upon their direct activation of replication-coupled signal
      transduction systems.

PMID- 7578802
TI  - Heterogeneity of endothelium-dependent mechanisms in different rabbit arteries.
AB  - The possible endothelial factors involved in endothelium-dependent relaxations
      induced by acetylcholine (ACh) in aorta, mesenteric and femoral arteries of
      rabbit were analyzed. In thoracic aorta precontracted with noradrenaline, NG
      nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB), inhibitors of
      nitric oxide (NO) synthase and guanylate cyclase, practically abolished ACh
      relaxation. This relaxation was reduced by the Na+ pump inhibition with ouabain
      and K(+)-free solution, and by the blockade of Ca(2+)-dependent K+ channels with
      tetraethylammonium (TEA). Ouabain reduced the relaxation produced by the NO
      donor, sodium nitroprusside (SNP). In the mesenteric artery, L-NAME and MB
      produced a small reduction of ACh relaxation. However, ouabain, K(+)-free medium
      and TEA markedly decreased this relaxation. SNP induced a relaxation which was
      diminished by ouabain. In segments precontracted with high K+, ACh relaxation was
      abolished by L-NAME and MB. In femoral arteries, L-NAME and MB reduced ACh
      relaxation. The stimulated cGMP concentrations caused by ACh or SNP were less in
      the aorta than in mesenteric and femoral arteries. These results suggest that ACh
      relaxation is mediated: in aorta by endothelial NO which may hyperpolarize to
      some extent the smooth muscle cells through the sodium pump activation, in
      mesenteric artery by endothelium-derived hyperpolarizing factor and NO, the
      latter being clearly expressed in segments contracted with high K+, and in
      femoral artery essentially by endothelial NO release.

PMID- 7578804
TI  - Molecular dynamics simulations of thrombin inhibitors at the S' subsites of
      thrombin.
AB  - Molecular dynamics were carried out to simulate binding interactions between S'
      subsites of thrombin and hirudin-based thrombin inhibitors. These inhibitors
      include three segments: an active-site segment, N alpha-acetyl-(D-Phe)-Pro-Arg
      Pro-; a fibrinogen-recognition exo-site segment, hirudin 55-65; and a 13-atom
      long linker. These linkers have been reported (Szewczuk et al. (1993)
      Biochemistry 32, 3396) to influence the binding potency while keeping the same
      active and exo-site segments. The study found that, by combining different omega
      amino acids, the potency could be increased 8-fold or decreased 4-fold compared
      to the native hirudin linker, -Gln-Ser-His-Asn-Asp-Gly-. Five typical linkers
      were simulated and compared. Analyzing the trajectory files led to the
      classification of three different dynamic behaviours for the linkers. The
      flexible linkers had no influence on the antithrombin activity. Other linkers
      formed hydrogen bonds with the thrombin S' subsite residues Glu39, leu40, and Gln
      151. Formations of some hydrogen bonds enhanced the potency of the inhibitor. In
      other cases, the hydrogen bonds caused the distortion of the inhibitor
      conformation while affected the binding potency. Based on these observations, a
      general binding mode in the S' subsites of thrombin is proposed and potential
      applications are discussed.

PMID- 7578803
TI  - Effect of captopril on acetylcholine-induced relaxation in the presence of
      nitroglycerin tolerance in isolated rabbit aorta.
AB  - We investigated the effects of angiotensin converting enzyme inhibitors on
      acetylcholine-induced endothelium-dependent vasodilation in the presence of
      nitroglycerin tolerance in rings of rabbit thoracic aorta mounted in tissue baths
      and precontracted with 10(-6) M norepinephrine. The vasorelaxant effects of
      acetylcholine were measured before and after 1 h treatment with 5 x 10(-4) M
      nitroglycerin. The acetylcholine dose-response curve shifted to the right after
      the induction of nitroglycerin tolerance. Pretreatment with captopril (a
      sulfhydryl angiotensin converting enzyme inhibitor), but not with M-1 (a
      metabolite of delapril and a nonsulfhydryl angiotensin converting enzyme
      inhibitor) restored acetylcholine-induced relaxation. Pretreatment with N
      acetylcysteine also restored reduced acetylcholine-induced relaxation. These
      results suggest that the sulfhydryl group plays a major role in restoration of
      reduced acetylcholine-induced vasodilation in the presence of nitroglycerin
      tolerance.

PMID- 7578805
TI  - Cytotoxic evaluation of some N-acyl and N-acyloxy analogues of 3,5-bis(arylidene)
      4-piperidones.
AB  - The preparation of thirteen N-acyl and N-acyloxy analogues of two 3,5
      bis(arylidene)-4-piperidones were prepared as potential prodrugs of the parent
      ketones. Approximately half of the compounds demonstrated antileukemic properties
      when evaluated against murine L1210 lymphoid leukemia cells. Three of the
      derivatives were more active than or equipotent with the reference drug
      melphalan. All of the compounds were examined against approximately 55 human
      tumours representing eight different neoplastic diseases. Not only were most of
      the compounds more cytotoxic than melphalan but 60% of the derivatives displayed
      selective toxicity to leukemia. A stability study of six of the candidate
      prodrugs using 1H NMR spectroscopy revealed that while some decomposition in
      solution occurred, the parent amine was not liberated.

PMID- 7578806
TI  - 3D-QSAR of human immunodeficiency virus (I) protease inhibitors. III.
      Interpretation of CoMFA results.
AB  - Comparative Molecular Field Analysis (CoMFA), a three-dimensional quantitative
      structure-activity relationship (3D-QSAR) paradigm (Cramer, R.D.; et al. (1988),
      J. Am. Chem. Soc., 110, 5959-5967), correlates variations in the (experimental)
      biological activity with 3D variance in the steric and electrostatic field of
      modeled compounds. Of general interest to the drug design area is the
      interpretation of CoMFA results, in order to gain maximum benefit from an
      established 3D-QSAR model. CoMFA studies report results using the standard
      deviation (stdev) times(*) coefficient (beta) field and its contributions to make
      SAR statements. This field is the scalar product of the absolute stdev of the
      CoMFA field at a lattice point and the QSAR equation coefficient (beta) at the
      same point. Negative beta values yield detrimental contributions, while positive
      beta values are considered beneficial. The QSAR equation is based on actual field
      values, therefore both positive and negative field values can have beneficial
      effect to the target property (Y), depending on the sign of beta. The results of
      a CoMFA model on 59 HIV-1 protease (HIV-PR) inhibitors (Waller, C.L.; et al.
      (1993), J. Med. Chem., 36, 4152-4160) were compared with the HIV-PR crystal
      structure to analyze the correspondence between CoMFA fields and ligand binding
      regions in the enzyme. Local steric and electrostatic interactions were analyzed
      in terms of various field values and beta coefficients. While redundant for some
      regions, other field contours besides stdev* beta bring additional information.
      Using this method, we observed a unique region with negative beta values for the
      electrostatic field (based on a -1 charged probe) located opposite of the
      scissile bond, between P1 and P1', where steric stdev* beta values are positive.
      Four hydrophobic residues in the HIV-PR crystal delimit the region, which is
      suggested as a new potential hydrophobic binding site for the inhibitors. The
      same region was confirmed using the stdev* beta contours of a HINT (Kellogg, G.;
      et al. (1991), J. Comput.-Aided Mol. Design, 5, 545-552) calculation on the same
      model. The steric, electrostatic and lipophilic fields of the CoMFA and HINT
      models are presented in various forms, and the information extracted is detailed.

PMID- 7578807
TI  - Synthesis and biodistribution of [4-14C]-5-bromo-6-methoxy-5,6-dihydro-prodrug
      derivatives of 5-ethyl-2'-deoxyuridine.
AB  - The radiochemical syntheses of the [4-14C]-(-)-trans-(5S,6S)-5-bromo-5- ethyl-6
      methoxy-5,6-dihydro-2'-deoxyuridine [2,(5S,6S)-BMEDU] and (+)-trans-(5R,6R)-5
      bromo-5-ethyl-6- methoxy-5,6-dihydro-2'-deoxyuridine [3,(5R,6R)-BMEDU] are
      reported. These BMEDU diastereomers were synthesized in 21 and 25% radiochemical
      yield, respectively, by direct addition of methyl hypobromite to the 5,6-olefinic
      bond of [4-14C]-5-ethyl-2'-deoxyuridine (EDU). The biodistributions of [4-14C]
      labelled diastereomers of 2 and 3, and EDU were determined in male Balb-C mice.
      The uptake of radioactivity in brain after injection of [4-14C]-BMEDU
      diastereomers of 2 and 3 was not significantly different than that of [4-14C]-EDU
      (P > 0.05). However, clearance of radioactivity from blood was substantially
      faster after injection of [4-14C]-EDU relative to the [4-14C]-BMEDU
      diastereomers. Liver samples, obtained after injection of the [4-14C]-BMEDU
      diastereomers, showed a higher percentage uptake of the injected dose per gram of
      tissue relative to liver samples obtained after injection of [4-14C]-EDU.

PMID- 7578809
TI  - Molecular modelling of known non-steroidal inhibitors of 17 alpha
      hydroxylase/17,20-lyase using antimycotic compounds.
AB  - A molecular modelling study is described for the binding of non-steroidal anti
      mycotic inhibitors of 17 alpha-Hydroxylase/17,20-Lyase (P450(17)alpha) to the
      enzyme active site. The study suggests that, after an initial binding of the
      nitrogen ligand with the Fe3+ haem of the P-450 cytochrome, the inhibitors
      containing hetero atom-substituted phenyl rings probably utilise a common binding
      site with ring A of the steroidal substrates, whereas for inhibitors devoid of
      hetero atoms, hydrophobic interactions become important.

PMID- 7578808
TI  - 'Peptoid' design.

PMID- 7578810
TI  - [Helicobacter pylori and non-ulcerous dyspepsia++].

PMID- 7578811
TI  - [Chronic gastritis and Helicobacter pylori in patients with non-ulcerous
      dyspepsia. Role and significance of age].
AB  - Patients with recurrent upper abdominal complaints and without peptic ulcer or
      definite evidence of organic disease have been labelled as suffering from
      nonulcer dyspepsia and included in the study. A total of 125 patients were
      studied and upper gastrointestinal endoscopy performed. Histology, urease rapid
      test and ELISA serology were done in order to detect Helicobacter pylori
      infection. Age groups were done. The most frequent endoscopic and histological
      finding was chronic gastritis in all age groups of patients. In patients under 30
      years old, the highest rate of normal endoscopy was found. Chronic gastritis was
      associated with Helicobacter pylori infection in 89.8% of all patients. The
      highest rate of chronic gastritis non associated with Helicobacter pylori
      infection was found in the age group of patients younger than 30 years old. Other
      factors as biliary reflux, gastroduodenal dismotility, decreased pain tolerance
      or stress have been proposed to be the etiology of chronic gastritis in young
      patients.

PMID- 7578812
TI  - [Antral biopsy in the prevention of gastric disease].
AB  - Approximately 1% of the gastric neoplasies are nowadays associated with the
      infection of the gastric mucus by Helicobacter pylori. In view of the fact that
      its prevalency is very high and that it does not exist any objective and
      universal estimator in its diagnosis but the digestive endoscopy and biopsy, it
      is proposed, in candidate patients for a digestive endoscopy, although the
      explorer observes an endoscopic normality, to carry out, systematically, and
      antral biopsy for its subsequent diagnosis, treatment and prevention both of the
      gastric pathology and the infection by Helicobacter pylori.

PMID- 7578814
TI  - [Geriatrics seen from the primary care perspective].
AB  - PURPOSE: To know the Primary Care Physicians opinion related to their own praxis,
      background, and needs for a specific medical support in geriatric medicine.
      METHODS: A closed mailed questionnaire, with 22 items. Descriptive analysis of
      the results. PEOPLE SAMPLE: 559 answers. 77% men. Age: main group (44%) between
      35 and 39 years old. 80% of the sample worked in health centers as primary care
      physicians. RESULTS: a) Praxis: 50% of the physicians attend more than 20 elderly
      patients every day. 38% of them have specific aged oriented protocols. 74% of
      them take age into account when decide the appropriate doses of drugs. b)
      Geriatric background: None at the undergraduate period: 96%. Some sort of
      postgraduate formation: 42%. Are able to identify at less a geriatric book: 34%.
      A score of 4.5 (over 10) was the result of their own assessment about their level
      of geriatric knowledge. 95% of the answers miss a better formation in geriatrics,
      and 93% of them think that this formation would change their clinical approach to
      the elderly patient. c) Needs of specialized geriatric support: It would be
      helpful to them according to a 84% of the answers. It could be as a "Geriatric
      Inhospital Service" in the opinion of a 44% of the cases (this question had a 18%
      of abstentions); and with geriatricians working as extrahospitalary consultants
      according to the answers of the 79% (6% of abstentions). CONCLUSIONS: Primary
      care physicians have: 1. Many elderly patients, with an acceptable level of
      attention to them. 2. A poor geriatric formation and awareness of their needs. 3.
      Need of a specialized support in their daily work.

PMID- 7578813
TI  - [The ASA index as an indicator of nosocomial infection risk in non-surgical
      patients].
AB  - OBJECTIVE: To determine the relation between health status of patients from a non
      surgical unit, measured with the ASA score, and the presence on nosocomial
      infection (NI). MATERIAL AND METHOD: Our ability to measure the health status
      with the ASA score was done with a sample of 150 surgical patients, using the
      Kappa test for interobserver agreement. We assigned the ASA score both cases
      (patients with NI) and controls to evaluate health status ad admission in the
      Internal Medicine Unit of our hospital. Statistical analysis was performed with
      the Mantel-Haenszel chi-square test, odds ratio (OR) and its 95% confidence
      interval (95%OR(CI)), and the chi-square test for linear association. RESULTS: We
      observed a global kappa value of 0.81 (p < 0.1), that meant high agreement in ASA
      score assignation, and statistical association between health status and the
      presence of NI (Weighted MH(OR) = 4.88; 95%OR(CI): 2.34-10.19). CONCLUSION:
      Health status, measured with the ASA score is statistically related with the
      presence of NI in non-surgical patients and could be useful as a comparison
      indicator of different levels of NI.

PMID- 7578815
TI  - [Diffuse lung hemorrhage and necrotizing glomerulonephritis in a case of
      Wegener's granulomatosis. Diagnostic and therapeutic approach].
AB  - We present the case of a 59 years old male with Wegener's Granulomatosis with
      uncommon manifestations such as diffuse pulmonary hemorrhage and acute renal
      failure due to necrotizing glomerulonephritis. Neutrophil anticytoplasmic
      antibodies determination was negative. Conventional and high resolution thoracic
      computed tomography showed cavitated lung nodules with small peripheral vessels.
      These lesions, that are characteristic of this type of vasculitis, were not
      appreciated on the routine chest roetgenogram. Definitive diagnosis was made by
      the histological study of open lung and renal biopsies. Favourable response to
      corticosteroids, immunosuppressive drugs and hemodialysis was obtained. Diffuse
      pulmonary hemorrhage is an uncommon manifestation of Wegener's Granulomatosis,
      and must be considered as a vital emergency that justify the use of aggressive
      diagnostic and therapeutic methods.

PMID- 7578816
TI  - [Eosinophilic fasciitis: its relationship with L-tryptophan ingestion].
AB  - The tryptophan ingestion has recently been involved in the etiology of the
      eosinophilia-myalgia syndrome. The common findings shared by eosinophilic
      fasciitis (EF) and that syndrome has suggested a possible role of tryptophan
      consumption in the development of both diseases. We report two cases of EF whose
      onset was likely attributed to tryptophan ingestion. Healing was achieved in both
      patients: the first one had a spontaneous remission and the second patient
      received glucocorticoid treatment. The EF pathogenesis is yet unknown as the
      tryptophan role involved in its development. It is likely that tryptophan could
      release some metabolic factor that support the patient propensity to this
      illness. It is remarkable to search for the possible tryptophan ingestion in
      every patient who presents a sclerodermiform syndrome, particularly in EF
      patients.

PMID- 7578817
TI  - [Splenic abscess following gynecologic infection with complete response to
      antibiotic treatment].
AB  - A 37 year old woman is presented with solitary splenic abscess, without
      involvement of other organs, in the context of septic abortion. Splenic abscess
      were effectively treated with 21 days of antibiotic administration, not was
      necessitated splenectomy and percutaneous drainage. Emphasis is laid on its
      rarity of solitary splenic abscess in the course of gynecologic infection, and
      complete response to antibiotic treatment.

PMID- 7578818
TI  - [Severe heart failure and skin lesions caused by Salmonella virchow. Report of a
      case].
AB  - We describe a case of congestive heart failure caused by a Salmonella virchow
      sepsis. Concurrent with this there were considerable skin lesions. The diagnosis
      was made as result of stool and skin biopsy culture. There was a good response to
      treatment.

PMID- 7578819
TI  - [Skin metastases, unusual presentation of lung cancer].
AB  - The existence of metastasis by lymphatic or hematogenous dissemination, is a
      regular fact during the course of bronchogenic carcinoma; they were described in
      different parts of the organism, those regular parts of metastasis are:
      suprarenals glands, liver, brain, contralateral lung and bone; however the
      presentation of cutaneous metastasis as first manifestation of lung cancer is
      infrequent. We revise the literature and we present two cases, remitted from the
      Service of Surgery in which the were studied for subcutaneous tumor of new
      appearance.

PMID- 7578821
TI  - [Quality of life (EuroQol)].

PMID- 7578822
TI  - [Psoriatic glomerulonephritis].

PMID- 7578820
TI  - [Nitric oxide in the lower respiratory tract].
AB  - The aim of this work is to review of the role of nitric oxide (NO) in the lower
      respiratory tract. This review mainly focuses on the generation of nitric oxide
      by alveolar macrophages. In the first part of the paper, we summarize the
      literature on nitric oxide synthesis by different cell types and the effects of
      this mediator on target cells. Methods for measuring nitric oxide are also
      analyzed. The core of the paper is a review of the role of nitric oxide in
      diffuse interstitial lung diseases (both human and experimental models). We
      include data about the concentration of this mediator in bronchoalveolar lavage
      fluid and then summarize the knowledge about the regulation of nitric oxide
      synthesis by animal or human alveolar macrophages. Finally, we review the
      biological effects of nitric oxide in the lower respiratory tract.

PMID- 7578823
TI  - [Endoscopic exploration of the entire bronchial tree in patients with unilateral
      radiologic lesion].

PMID- 7578824
TI  - [Nephrotic syndrome resolved following excision of epidermoid carcinoma of the
      lung].

PMID- 7578825
TI  - [Rhabdomyolysis secondary to moderate physical exercise].

PMID- 7578826
TI  - [Tetany caused by foscarnet in a female patient with acquired immunodeficiency
      syndrome].

PMID- 7578827
TI  - [Spontaneous retroperitoneal hemorrhage].

PMID- 7578828
TI  - [Treatment of idiopathic thrombopenic purpura with danazol].

PMID- 7578829
TI  - [Meningitis caused by Listeria in immunocompetent patients].

PMID- 7578830
TI  - [Training of the family physician in the rational use of drugs].

PMID- 7578831
TI  - [Promotion of mother-infant health: a comparative study of legislation of
      pregnancy protection].
AB  - OBJECTIVE: To describe the legislative measures aimed at protecting working women
      during pregnancy, which exist in France, Italy, the United Kingdom and Spain.
      DESIGN: The aspects studied were employment protection and modifications in work
      conditions for the pregnant woman. Existing Spanish legislation, the third
      Programme of Community Action for Equal Opportunities and some relevant
      scientific articles were reviewed. MEASUREMENTS AND MAIN RESULTS: Regarding
      protection of pregnant women from dismissal, legislation is more explicit in
      France and Italy, where protection covers the whole of the pregnancy, extending
      in France until 4 weeks after the end of the period off-work for the birth and in
      Italy until the child is one year old. Likewise, both in France and Italy, there
      is a long list of jobs which a pregnant woman is not allowed to do, with the
      possibility of a change of post if necessary. In Spain there is a Health at Work
      draft law, where measures relating to this question have been assembled.
      CONCLUSION: In general, the legislation referring to the protection of pregnant
      women at work is not widely known and leaves without protection those women in a
      more vulnerable work situation. Health professionals could support the equality
      and health of working women by informing them adequately of their rights.

PMID- 7578832
TI  - [Importance of HDL cholesterol determination in the evaluation of coronary risk
      in clinical practice].
AB  - OBJECTIVE: To validate to what extent the isolated determination of total
      Cholesterol (TC) is effective when seeking to predict coronary risk. DESIGN: An
      observational crossover study of the analytic determinations of the clinics which
      systematically request TC and HDL-Cholesterol (HDL)--case-finding method.
      SETTING: Health Centre. PARTICIPANTS: 631 analytic determinations, with samples
      from people who attended a Health Centre between May and November 1992, were
      studied. MEASUREMENTS AND MAIN RESULTS: As proof of certainty the Atherogenic
      Index (AI) was used for the relative risks (RR) of suffering a coronary event in
      line with the Framingham study. The confidence limits (CL) were calculated to 95%
      in order to quantify random error and permit comparison. On varying the cut-off
      points of TC the indicators changed, being more sensitive (S) and less specific
      (E) with the lower figures: 180 mg/dl, RR > 1, S = 97.5% (CL: 100-94.7) and E =
      30.5% (36.8-24.2); RR > 2, S = 100%, E = 22.1% (26.9-17.3) and RR > 3, S = 100%,
      E = 20.8% (25.3-16.3). As values of TC increase, S diminishes and E increases:
      250 mg/dl, RR > 1, S = 48.3% (57.2-39.4), E = 87.2% (91.8-82.6); RR > 2, S =
      58.6% (76.5-40.7), E = 77.2% (82-72.4) and RR > 3, S = 63.6% (92-35.2), E = 75.3%
      (80.1-70.5). CONCLUSIONS: HDL must be determined if TC is -200 mg/dl. If everyone
      with RR > 2 is to be detected, HDL-cholesterol from TC > or = 180 mg/dl must be
      measured.

PMID- 7578833
TI  - [Winter epidemic of carbon monoxide poisoning in Badia].
AB  - OBJECTIVE: To find the incidence, morbidity and possible causes of the acute
      carbon monoxide poisonings (ACMP) which occurred in Badia between january 1992
      and june 1993. DESIGN: A longitudinal, retrospective study. PATIENTS: Every Badia
      resident discharged from the Hospital Consortium of Parc Tauli, Sabadell with a
      diagnosis of ACMP and/or from Barcelona's Red Cross Hospital (RCH) after
      hyperbaric treatment was considered. MEASUREMENTS AND RESULTS: Cases were
      identified using the hospital discharge records from Parc Tauli and the RCH. A
      systematic review of the primary care clinical records was undertaken. The causes
      of the poisoning were investigated by a technical committee and through the gas
      company carrying out inspections of dwellings in 1993. The incidence of ACMP was
      76.5 per 100,000 inhabitants in 1992 and 109.4 per 100,000 in the first half of
      1993. 94% of the 34 cases occurred in December, January, February and March. 50%
      of those affected were under 17. The number of cases per household varied between
      2 and 5 people. The most common underlying cause was the existence of defects in
      the conduits taking fumes away from gas heaters. The gas review detected defects
      in installation in 54% of dwellings. CONCLUSIONS: ACMP is a common and serious
      problem in our environment. The underlying causes and the high number of
      dwellings at risk have suggested a need for information campaigns in the
      community.

PMID- 7578834
TI  - [Analysis of hypercholesterolemia care costs in primary health care].
AB  - OBJECTIVES: 1) To calculate the care costs of Hypercholesterolaemia in Primary
      Care in terms of the number of visits to the doctor, analyses and drugs. 2) To
      calculate the effectiveness of the intervention. DESIGN: A retrospective study.
      SETTING: Primary Care Centre. PATIENTS: 97 histories of patients diagnosed as
      having Hypercholesterolaemia, obtained by systematic sampling from the Centre's
      morbidity register, were analysed. A control with the same age, sex and risk
      factors was chosen for each one of them. MEASUREMENTS: The study period was 12
      months. For those patients diagnosed as having Hypercholesterolaemia after the
      opening of the centre, the initial figures and those at the end of the study for
      total Cholesterol, LDL Cholesterol (cLDL) and HDL cholesterol (cHDL) were
      analysed. RESULTS: There were no differences between the demographic
      characteristics and the risk factors of the cases and controls. An excess of
      attendances (average of 9.0 against 6.0, p = 0.01), of hypolipaemic and non
      hypolipaemic drugs (average of 4.0 against 3.0, p = 0.006) and of analyses
      (average of 2.0 against 0.0, p = 0.0001) were detected for the cases. The
      following variations were found between the initial and final figures: for total
      Cholesterol (-7.2%, p = 0.001), for cLDL (-11.6%, p = 0.006) and cHDL (+18.2%, p
      < 0.0001). CONCLUSIONS: 1) Hypercholesterolaemia care in a mainly selective
      manner for people at high risk was shown to be reasonably effective and
      affordable. 2) Before starting other strategies for detecting
      Hypercholesterolaemia, adequate prioritisation and evaluation of their impact on
      health-care delivery are required.

PMID- 7578835
TI  - [Insomnia in general practice: the opinion of the patient and the professional].
AB  - OBJECTIVES: Although insomnia is a common complaint in Primary Care, the
      patient's perception of the problem and the variables which affect his/her visit
      to the doctor have been little studied. In this study the Subjective Complaint of
      Insomnia (SCI) was evaluated. These data were then compared with those found in
      the clinical records and those contributed by the doctors at a Health Centre.
      DESIGN: An observational crossover study, using a structured personal interview
      based on Goldberg's Clinical Interview Schedule, was carried out. The clinical
      records of those interviewed were reviewed and a questionnaire aimed at the
      doctors was designed to determine their perception of insomnia from their
      consultations. RESULTS: The prevalence of SCI in the preceding week was 45.45%.
      45.7% of patients with SCI attended for this reason. Those patients who did not
      declare SCI to their doctor often lacked psychiatric antecedents, attended
      because of acute (rather than chronic) pathology and scored lower on the
      subjective evaluation scale of the intensity of the insomnia. Quality of sleep
      was recorded in 58.7% of the clinical records, with 20.6% prevalence of insomnia.
      All the doctors interviewed thought that the prevalence of insomnia among their
      patients was below 40%. CONCLUSIONS: The prevalence of insomnia in Primary Care
      is greater than doctors believe and than that recorded in the clinical notes.
      Patients who do not mention their problems are those who are less seriously ill.

PMID- 7578836
TI  - [Treatment of pain and anxiety in terminal oncologic patients in the Castilla-La
      Mancha community].
AB  - OBJECTIVE: To find what palliative treatment, in particular for pain and anxiety,
      terminal cancer patients in the Community of Castilla La Mancha receive. DESIGN:
      A descriptive, retrospective study by means of a questionnaire. SETTING: Primary
      Care. Autonomous Community of Castilla La Mancha. PATIENTS AND OTHER
      PARTICIPANTS: A survey of 157 doctors with data referring to their last cancer
      patient deceased in the period from January to August, 1994. MEASUREMENTS AND
      MAIN RESULTS: Data on 157 patients were received. Of all the tumours, lung cancer
      was the most common (22.93%). Pain was the symptom most often mentioned (92.91%);
      anxiety appeared in 70.06%. The most commonly used non-opiate analgesic was
      Paracetamol (58.22%). Morphine was used in 46.48%, for an average period of 2.35
      months (SD = 2.21). Side-effects due to morphine appeared in 22.06%.
      Complementary drugs to treat pain were used in 13.01% of cases. 12% were referred
      to specialists for analgesic control. Doctors used pain measurement tables in
      5.48% of cases. 19.09% of patients suffering anxiety received no type of
      treatment. CONCLUSIONS: We think that analgesic tables to monitor the treatment
      should be used. Attention should be paid to the appearance of side-effects of
      morphine, the circulation of pain graduation tables and the evaluation of anxiety
      in this category of patient.

PMID- 7578838
TI  - [Computerization: equipment, attitudes and aptitudes at health centers of the
      Autonomous Basque Community].
AB  - OBJECTIVE: To find the material complement, skills and attitudes towards
      computers of professionals working in the Primary Care field in the Basque
      Autonomous Community. DESIGN: A descriptive study based on a personal
      questionnaire. SETTING: Primary Care Centre of Osakidetza-Basque Health service.
      MAIN RESULTS: Overall reply rate was 83.5%. The actual hardware complement was
      only 8% of that required. Hardware needs were calculated as 89 regular and 6
      occasional outlets for each 100 professionals. A minimum of 27% of the network's
      professionals already used a computer. About 2,000 people needed first-contact
      training. Proficiency training needs oscillated between 25 and 50% of the staff
      in function of the type of software. CONCLUSIONS: There is a significant
      equipment deficit. Professionals are highly sensitised to the reality of
      computerisation, as both the high rate of reply and the desire to acquire
      computer literacy confirm.

PMID- 7578837
TI  - [Analysis of prescriptions of antibiotics for acute respiratory infections at a
      health center].
AB  - OBJECTIVE: To analyse the prescription of antibiotics for acute respiratory
      infections (ARI) at our Health Centre. DESIGN: An observational crossover study.
      SETTING: Primary Health care. San Gregorio de Telde Health Centre, Gran Canaria.
      PATIENTS AND PARTICIPANTS: Systematic random sampling of 368 clinical cases with
      ARI. 196 women (53.26%) and 172 men (46.73%), with an average age of 33.26 +/-
      1.97. MEASUREMENTS AND MAIN RESULTS: Antibiotics were prescribed for 42.66% of
      ARI. Family doctors used them less than general ones (38.67% against 63.04%, p <
      0.0001), and on the afternoon lists they were used less than in the morning
      (33.82% against 52.35%, p < 0.001). In chronically ill patients they were used
      less than symptomatic treatment (42.16% against 57.83%, p < 0.001). There were no
      significant differences found between their use and the appearance of
      complications (37.5% with Antibiotherapy against 62.5% without it) or successive
      consultations (45.16% with antibiotics against 54.83% without them). They were
      used more in those aged over 60 (48.97%) and in those who attended less (51.56%).
      Average cost per patient treated with Antibiotherapy was 2,508.48 +/- 258.80
      pesetas against 694.28 +/- 78.67 pesetas for the patient treated symptomatically
      (p < 0.0005). CONCLUSIONS: We are using Antibiotherapy inadequately in our field.
      We propose that quality control studies to detect and correct problems of this
      type should be undertaken. In our case corrective measures with a later
      reevaluation should be applied.

PMID- 7578839
TI  - [Training of nurses in primary health care: international experience in community
      health].

PMID- 7578840
TI  - [Bioethics and terminal illness].

PMID- 7578842
TI  - [Usefulness of maximal expiratory flow in the diagnosis of occupational asthma].

PMID- 7578841
TI  - [Amoxicillin: choice in the treatment of acute otitis media].

PMID- 7578843
TI  - [Evaluation of blood pressure monitors].

PMID- 7578844
TI  - [Serum sickness type reaction to citiolone].

PMID- 7578847
TI  - [Library records].

PMID- 7578845
TI  - [Computers and quality: a practical example].

PMID- 7578848
TI  - Influence of deletion of T cell receptor V beta genes on the Theiler's virus
      model of multiple sclerosis.
AB  - To determine the role of TCR V beta genes in a model of multiple sclerosis (MS),
      we studied Theiler's virus infection in congenic mice with deletion of TCR V beta
      chromosome. Congenic mice expressing the V beta a [50% deletion of TCR V beta] or
      V beta c 70% deletion of TCR V beta] haplotype were generated in mice resistant
      [B10 (H-2b)], intermediate [B10.K (H-2k), B10.RIII (H-2r)] or susceptible [B10.S
      (H-2s), and B10.Q (H-2q)] to Theiler's virus induced demyelination. Deletion of
      TCR V beta genes (V beta a or V beta c) did not convert B10 or B10.K congenic
      mice to susceptibility. In contrast, congenic B10.RIII-V beta c developed
      prominent demyelination and 10- to 100-fold increase in virus-antigen expression
      in spinal cord compared to B10.RIII mice. No effect on the extent of
      demyelination was observed in B10.S-V beta a, B10.S-V beta c or B10.Q-V beta c
      mice. These experiments illustrate the critical interactions between MHC, TCR,
      and background genes in susceptibility to immune-mediated disease.

PMID- 7578846
TI  - [Prognostic value of AFP in chronic carriers of HBsAg with Down's syndrome].

PMID- 7578850
TI  - Nitric oxide production is not involved in the effects of interleukin-1 beta on
      cAMP, thyroglobulin and interleukin-6 in TSH-stimulated human thyroid cells.
AB  - Interleukin (IL)-1 inhibits the function of insulin-producing rat pancreatic beta
      cells in vitro and in vivo, and it has been postulated that the IL-1 effect is
      mediated through the cytokine inducible nitric oxide (NO) synthase. IL-1 inhibits
      the function of cultured human thyroid cells too, and in this study human thyroid
      cell production of NO in response to the TSH-stimulated influence of IL-1 beta
      (10(5) U/l) and TNF-alpha (10(6) U/l), alone or in combination was measured. IL-1
      beta, but not TNF-alpha, induced an increase in nitrite production, which was
      significantly reduced by the competitive inhibitor of nitric oxide synthase L-NG
      monomethyl-arginine (L-NMMA) (0.1 mmol/L and 0.5 mmol/L). However, the nitrite
      production was unrelated to the IL-1 beta-induced inhibition of thyroglobulin
      (Tg) and cyclic AMP (cAMP) and the IL-1 beta-induced IL-6 production. Thus, it is
      unlikely that NO is a second mediator of the demonstrated effects of IL-1 beta
      and TNF-alpha on human thyroid cells in culture.

PMID- 7578849
TI  - Association between antibodies to the MR 67,000 isoform of glutamate
      decarboxylase (GAD) and type 1 (insulin-dependent) diabetes mellitus with
      coexisting autoimmune polyendocrine syndrome type II.
AB  - By using an immunoprecipitation assay, we analysed reactivity of autoantibodies
      to human recombinant GAD65 and GAD67 in sera from patients with autoimmune
      polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin
      dependent) diabetes mellitus (IDDM) compared to patients with organ-specific
      autoimmunity. Overall antibodies to GAD65 were correlated with IDDM in all study
      groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists.
      Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29
      APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II
      patients without IDDM, respectively (p < 0.05). In short-standing IDDM (< 1
      year), antibodies to GAD67 were significantly more frequent in patients with APS
      II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without
      coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). The levels of
      GAD65 (142 +/- 90 AU) and GAD67 antibodies (178 +/- 95 AU) were significantly
      higher in patients with polyglandular disease than in patients with isolated IDDM
      (91 +/- 85 AU and 93 +/- 57 AU) (p < 0.02). Interestingly, all 11 GAD67 antibody
      positive subjects also had GAD65 antibodies (p < 0.0001), and in 10 of 11 anti
      GAD67 positive sera the GAD67 antibodies could be blocked by either GAD67 or
      GAD65, suggesting the presence of cross-reactive autoantibodies. No correlation
      was observed between GAD antibodies and age, sex or any particular associated
      autoimmune disease, besides IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578852
TI  - Regulation of ornithine decarboxylase in the kidney of autoimmune mice with the
      lpr gene.
AB  - The lymphoproliferative lpr gene confers a lupus-like disease with
      lymphadenopathy, antinuclear antibody production, and glomerulonephritis in MRL
      lpr/lpr mice. Upregulation of ornithine decarboxylase (ODC) activity and
      polyamine levels have been observed in the kidney and lymphoid organs of this
      strain. Inhibition of ODC with 0.5-1.5% (w/v) difluoromethylornithine (DFMO) in
      drinking water prolonged life-span and ameliorated renal disease.
      Glomerulonephritis is a major cause of morbidity and mortality in human and
      murine lupus. In order to elucidate the mechanism(s) of ODC regulation in lupus
      nephritis, we characterized ODC at the protein and mRNA levels in 3 strains of
      autoimmune mice with the lpr genetic background (MRL-lpr/lpr, C3H-lpr/lpr and
      C57BL/6J-lpr/lpr) using Western blotting, enzyme kinetics, turnover rate
      measurements, Northern blot hybridization, and reverse transcription-polymerase
      chain reaction (RT-PCR). Normal BALB/c mice were used as a control. We found that
      ODC activity in the kidney of lpr strains was 4- to 6-fold higher than that of
      BALB/c mice. The intensity of the major ODC protein band at 54 kD in Western blot
      was 4-fold higher in MRL-lpr/lpr and C3H-lpr/lpr kidney compared to that of
      BALB/c kidney. Putrescine levels were 2- to 4-fold higher in kidney of lpr
      strains than that of BALB/c and DFMO-treated MRL-lpr/lpr mice. DFMO treatment
      significantly reduced ODC activity and polyamine levels. The half-life of ODC
      enzyme in MRL-lpr/lpr, C3H-lpr/lpr, B6-lpr/lpr and BALB/c mouse kidneys was 15,
      5, 8 and 23 min, respectively. There was no significant difference in the Km
      values of different strains, whereas Vmax values differed significantly. There
      was no difference in the level of SAMDC, another enzyme involved in the polyamine
      biosynthetic pathway, in various strain. Steady-state levels of ODC mRNA were
      lower in lpr strains compared to that of BALB/c mouse. Our results suggest that
      the basis for up-regulation of ODC is not at the transcriptional level, but may
      involve post-transcriptional modification(s) in lpr strains. The link between
      aberrant regulation of ODC and the immunopathogenesis of murine lupus nephritis
      indicates novel targets for lupus therapy.

PMID- 7578851
TI  - T-cell receptor polymorphisms in Tlingit Indians with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) develops as a result of the interaction of both genetic
      and environmental factors. Among the genes in humans that have been suggested as
      candidate susceptibility genes in RA are those encoding the T cell receptor for
      antigen (TCR). A high prevalence and early age of onset of RA has previously been
      reported in Alaskan Tlingit Indians. In this study, the frequency of seven
      different restriction fragment length polymorphisms (RFLPs) in the TCR alpha and
      beta gene complexes were measured in a population of Alaskan Tlingit Indians. No
      statistically significant differences were noted when the frequencies of these
      RFLPs were compared between Tlingits with RA and healthy controls (p > 0.05).
      These results do not support the hypothesis of an RA-susceptibility allele in the
      vicinity of these TCR alpha or beta genes. Since TCR RFLPs have not been
      extensively studied in native American populations, TCR polymorphism frequencies
      in the Tlingits were also compared to the frequencies observed in a second
      control group of healthy Caucasians. Statistically significant differences were
      observed in these comparisons implying a different distribution of individuals in
      these populations with different TCR repertoires.

PMID- 7578853
TI  - Autoantibody associations with MHC class II antigens in scleroderma and
      autoimmune vasculitis.
AB  - HLA-DR haplotypes in patients with scleroderma and vasculitis were compared with
      those in healthy controls from the Scottish population to investigate whether any
      associations exist between MHC antigens and development of specific
      autoantibodies. In patients with systemic vasculitis the presence of any
      antibodies against neutrophil cytoplasmic antigens (ANCA) was associated with an
      increased frequency of DR8 [p < 0.004], and no patients expressed the DR5
      antigen. However, no significant differences were observed when these patients
      were subdivided into those with anti-myeloperoxidase (MPO) antibodies or anti
      proteinase-3 (PR3) antibodies. Scleroderma patients as a whole showed a lower
      frequency of DR7 than controls [5.1% cf 28% in control population, p < 0.002].
      Following subdivision by autoantibody profile, patients with circulating anti
      centromere antibody (ACA) showed an increased frequency of DR1 compared to the
      control population [p < 0.001]. No scleroderma patient without ACA expressed this
      haplotype. Associations between MHC and some autoantibodies suggest that antigen
      presentation could lead to their production.

PMID- 7578855
TI  - Longitudinal changes of serum insulin concentration and insulin antibody features
      in persistent insulin autoimmune syndrome (Hirata's disease).
AB  - In a 56-year-old woman with granulomas of gold thioglucose in her hips, who
      developed insulin autoimmune syndrome, the relationships among the frequency or
      severity of hypoglycemic attacks, serum insulin (IRI) concentration, and
      characteristics of insulin antibodies were investigated during the clinical
      course with steroid treatment and two resection operations for the gold
      thioglucose granulomas. When hypoglycemia was severe, the total IRI level was
      elevated, and Scatchard analysis showed that a high-affinity (k1), low-capacity
      (b1) population of antibodies had a relatively low affinity constant and very
      high binding capacity compared with the same population of antibodies in insulin
      treated diabetic patients. When the attacks were relieved by steroid treatment
      and/or granuloma resection operation, the total IRI level was decreased and the
      high-affinity (k1), low-capacity (b1) population of antibodies showed a higher
      affinity constant and a lower binding capacity than those during the attacks.
      This indicated that the antibodies changed their characteristics to release
      insulin into the serum. The k1/b1 population of insulin antibodies with the lower
      affinity constant and higher binding capacity may easily release human insulin
      into the serum, leading to hypoglycemia. The longitudinal change of the k1/b1
      population suggests a clonal change of the B cells producing the insulin antibody
      in insulin autoimmune syndrome.

PMID- 7578856
TI  - Clinical significance of anticardiolipin antibodies in patients with systemic
      sclerosis.
AB  - One hundred and three patients suffering from systemic sclerosis (SSc), with
      different extent of skin involvement, were retrospectively examined to
      investigate the correlations between clinical manifestations and anticardiolipin
      antibodies (aCL). aCL of IgG, IgA, and IgM classes were measured in the patients'
      sera by enzyme linked immunosorbent assay. aCL were found in 26 patients (25.2%).
      A significant association was found between aCL and myocardial ischaemia or
      necrosis (p = 0.011). No patient showed the clinical picture of the
      antiphospholipid syndrome. On the basis of clinical manifestations, a protocol
      for disease score was drawn. Patients with IgG-aCL and with IgA-aCL showed a
      disease score higher than aCL negative patients (p = 0.008 and p = 0.022
      respectively). Thus, the finding of aCL can be considered a useful serological
      index for the most severe forms of SSc.

PMID- 7578854
TI  - Graves' disease thyroid tissue transplants in scid mice: persistent selectivity
      in hTcR Va gene family use.
AB  - We have analyzed the human T-cell receptor (hTcR) V alpha gene repertoire in
      thyroid tissue transplants of a patient with hyperthyroid Graves' disease. Blocks
      of thyroid tissue were transplanted subcutaneously into 10 mice with severe
      immunodeficiency (scid) and 4 weeks later 5 of the mice were injected
      intraperitoneally with autologous peripheral blood mononuclear cells (PBMC)
      (10(7) cells per mouse). After a further 3 weeks, mice were sacrificed and total
      cellular RNA and cDNA prepared from each of the explants. We used specific
      olingonucleotides in polymerase chain reactions (PCR) to amplify 18 different
      human hTcR V alpha gene families and the identity of the PCR fragments was
      confirmed by Southern blot analysis. Different samples of the donor thyroid
      tissue consistently expressed 9-10 of the 18 hTcR V alpha gene families screened
      (V alpha 1-7, 11, 12 & 15). A more marked bias in hTcR V gene family use was seen
      in each of the explants with a mean of only 2.8 V alpha gene families detected.
      After 7 weeks of transplantation, the thyroid explants largely reflected some of
      the same genes seen in the hTcR V gene repertoire of the donor tissue with
      particularly pronounced expression of V alpha 2 and V alpha 3 gene families. The
      transplantation of PBMC into the scid mice showed evidence for their accumulation
      within the transplanted thyroid tissues as judged by the appearance of additional
      hTcR V gene families expressed in these samples although the specificity of such
      accumulation remains unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578857
TI  - Beta cell-specific expression of retroviral mRNAs and group-specific antigen and
      the development of beta cell-specific autoimmunity in non-obese diabetic mice.
AB  - Non-obese diabetic (NOD) mice spontaneously develop autoimmune type 1 diabetes.
      Earlier studies have shown that retroviruses appear to be associated with the
      development of the disease in these animals. This investigation was initiated to
      determine whether any retroviral genes are specifically expressed in pancreatic
      beta cells from NOD mice, in contrast to their non-diabetic, parental strain, ICR
      mice. Host chromosomal DNAs from pancreatic islets, kidneys, hearts, and stomachs
      of NOD and ICR mice contained an equal amount of A-type retroviral genome (DNA);
      however, A-type retroviral gag, pol, and env mRNAs were detected in only the
      pancreatic islets from NOD mice. Furthermore, group-specific retroviral antigen
      (p73 of A-type--gag gene product) was found by immunofluorescent staining using
      anti-p73 antibody in only pancreatic beta cells from NOD mice. On the basis of
      these observations, we suggest that tissue and strain differences in
      transcription of the retroviral genome and beta cell-specific expression of A
      type retroviral group-specific antigen p73 in NOD mice may be involved in the
      initiation of beta cell-specific autoimmunity leading to type 1 diabetes in these
      animals.

PMID- 7578858
TI  - Serological abnormalities induced by engraftment of viable motheaten
      hematopoietic cells in nude beige recipients.
AB  - C57BL/6J (B6) mice homozygous for the viable motheaten (mev) mutation are short
      lived and display severe immunodeficiency, autoimmunity and inflammatory disease.
      B6 mice doubly homozygous for the nude (nu) and beige (bg) mutations (nubg mice)
      are also short-lived and immunodeficient. Nevertheless, grafts of mev lympho
      hematopoietic cells increased life expectancy of nubg recipients. Such [mev -->
      nubg] chimeras did not develop any mev-like inflammatory pathology but showed
      autoimmunity features, particularly hyperglobulinemia which, unlike the mev one,
      was due to IgG rather than IgM. Serological studies of [mev IgHb --> nubg Igha]
      chimeras surprisingly revealed the exclusive host B-cell origin of the IgG2a
      overproduced by these chimeras. Yet, about half of such chimera serum IgM being
      IgMb, mev B cells had actually engrafted the nubg hosts. Together with the lack
      of transfer of the inflammatory pathology, this suggests that a non-mev
      environment might succeed acting as a regulator of some mev-induced dysfunctions.

PMID- 7578859
TI  - Anti-neutrophil cytoplasm antibodies in patients with ACR criteria for
      polyarteritis nodosa: help for systemic vasculitis classification?
AB  - The american college of rheumatology (ACR) proposed in 1990 revised clinical
      criteria for systemic vasculitis classification to define homogeneous group of
      patients for clinical trials. However, microscopic polyarteritis (MPA) was not
      clearly identified from polyarteritis nodosa (PAN). Since anti-neutrophil
      cytoplasm antibodies (ANCA) are markers of disease activity of small vessel
      vasculitides including MPA, we tested the clinical significance of ANCA in 24
      patients with PAN according to the ACR 1990 criteria. Two of 24 patients had
      ANCA, as defined by indirect immunofluorescence on normal human neutrophils,
      antigen-specific ELISA and Western blot analysis. However, they exhibited
      histologically proven small vessel but not medium vessel vasculitis. Furthermore,
      they had neither artery microaneurysms nor large organ injury consequent upon
      large vessel occlusion. Although they satisfied ACR criteria for PAN, they
      probably were misclassified and should be considered as MPA. We conclude that:
      (i) ANCA are not found in patients with classical PAN in the absence of MPA
      features; (ii) caution should be exercised when defining PAN according to the ACR
      1990 criteria; (iii) ANCA may help systemic vasculitis classification.

PMID- 7578861
TI  - Altered development of collagen induced arthritis in T cell receptor V beta
      congenic B10.RIII mice.
AB  - Analysis of the mouse T cell receptor (TCR) V beta genome has revealed the
      existence of two distinct genotypes which bear deletions of certain V beta genes.
      Mice bearing the V beta a genotype lack approximately 50% of the V beta genome
      while V beta c mice lack 70% of the known V beta genes. Studies of the
      experimental model collagen induced arthritis (CIA) have indirectly suggested
      that the presence of truncated V beta genotypes may influence susceptibility to
      this autoimmune disease. In order to confirm the influence of V beta a and V beta
      c genotypes on CIA, we derived mice congenic for the known V beta haplotypes in
      the CIA susceptible B10.RIII (H-2r) background. Flow cytometric analysis of
      splenic lymphocytes revealed normal T cell levels in both B10.RIII-V beta
      congenic lines. Expectedly, a generalized increase in the expression of some non
      deleted V beta genes was detected. In addition, the mice were immunized with
      porcine type II collagen and monitored for CIA. B10.RIII-V beta a mice showed
      little difference in arthritis incidence or severity versus B10.RIII, but a
      significant delay in the onset of CIA was seen. In contrast, B10.RIII-V beta c
      mice showed a marked decrease in arthritis incidence versus B10.RIII and the
      severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus,
      in the B10.RIII strain, the presence of truncated TCR V beta genotypes alters the
      development of CIA. These findings may shed light on the influence of TCR
      genotypes in the induction and development of human rheumatoid arthritis.

PMID- 7578860
TI  - Identification of a cyanogen bromide fragment of porcine type II collagen capable
      of modulating collagen arthritis in B10.RIII (H-2r) mice.
AB  - Previous studies directed towards identifying epitopes on type II collagen (CII)
      important in collagen induced arthritis (CIA) in mice have focused primarily on
      responses mounted in susceptible H-2q strains. However, the nature of T and B
      cell responses against CII in susceptible H-2r strains remains ill-defined. In an
      effort to identify regions on CII important in CIA in H-2r mice, we examined the
      cellular and humoral response of susceptible B10.RIII (H-2r) mice against
      cyanogen bromide (CB)-cleaved fragments of porcine CII. Following immunization
      with native porcine CII, LNC from B10.RIII mice mounted proliferative responses
      predominantly to peptide CB10, while negligible proliferation was detected
      against fragment CB9, 7, CB8, CB11 or CB12. In contrast, sera from arthritic
      B10.RIII mice displayed a heterogeneous pattern of reactivity against porcine
      CII, with strong antibody binding measured against the major fragments CB11, CB8
      and CB10. To determine the in vivo significance of the dominant cellular response
      to CB10, B10.RIII mice received an i.v. injection of soluble CB10 seven days
      before immunization with native porcine CII. Mice pretreated with CB10 were
      highly resistant to CIA compared to control animals. Interestingly, B10.RIII mice
      pretreated with fragment CB11, a region of CII implicated in H-2q restricted CIA,
      remained susceptible to arthritis induction. Collectively, our findings indicate
      that the CB10 region of porcine C11 bears determinants which may be important in
      the induction and/or regulation of CIA in the H-2r haplotype.

PMID- 7578862
TI  - The relationship of anti-endothelial cell antibodies to anti-phospholipid
      antibodies in patients with giant cell arteritis and/or polymyalgia rheumatica.
AB  - Sera from patients with giant cell arteritis and/or polymyalgia rheumatica were
      tested for the presence of IgG, IgM and IgA antibody to endothelial cells (AEC),
      cardiolipin (ACL) and phosphatidylethanolamine (APE) using enzyme-linked
      immunosorbent assays. There were strong correlations between ACL and APE, but
      also between AEC and ACL IgM (p < 0.02) and between AEC and APE IgA (p < 0.003).
      Inhibition of AEC binding was achieved by absorption onto EC, but ACL and APE
      binding was also significantly reduced. In contrast, the binding of AEC antibody
      could not be inhibited by incubation with CL. Our data suggest that AEC
      constitute a heterogeneous population of autoantibodies.

PMID- 7578863
TI  - Alternative splicing and cDNA sequence of myelin basic protein gene of the Lewis
      rat.

PMID- 7578864
TI  - Inhibition of nitric oxide formation and prevention of type 1 diabetes.

PMID- 7578865
TI  - Interactions of B6 wild and B6 gld cells engrafted within athymic nude beige
      recipients.
AB  - The murine gld mutation is targetted to the gene coding for the ligand of the Fas
      receptor for apoptosis. Gld mice display a lymphoproliferative and autoimmune
      syndrome that can be transferred in both irradiated euthymic wild and athymic
      beige (nubg) recipients. In order to test whether a supply of normal wild cells
      could correct the development of the gld syndrome, nubg mice were grafted with
      mixtures of gld and wild spleen cells from congenic donors which differed for the
      allotypes of the T-cell Thy1 membrane glycoprotein and/or of the B-cell Ig heavy
      chain. In the nubg chimeras, the wild spleen cells could down-regulate the
      hyperactivation of the B cells and the proliferation of the gld T cells, but this
      was not due to total eradication of the gld T-cell subset. Since this occurred in
      an athymic recipient, the correction of the gld syndrome did not require wild
      stem cell differentiation within a thymic environment, but should only depend on
      a sufficient Fas ligand supply by normal wild cells. Since the gld cells could
      proliferate in the nubg environment, the nubg environment could not provide
      sufficient Fas ligand to regulate the gld cell proliferation. Thus, the nubg B
      cells might lack Fas ligand expression, or express it but to a lower extent that
      T cells.

PMID- 7578866
TI  - IgA antihistone antibodies in isoniazid-treated tuberculosis patients.
AB  - A retrospective study of tuberculosis patients treated with isoniazid was
      undertaken in order to establish the prevalence and specificity of antibodies
      against histones, chromatin and denatured DNA. Each patient had an average of 2.7
      +/- 0.4 antibody activities out of the 8 tested antigens using ELISA. These
      reactivities tended to be higher for non-native forms of the antigens such as
      denatured histones and DNA with essentially no reactivity to the (H2A-H2B)-DNA
      subunit of chromatin. Greater than half of the patients were isotype restricted
      to only IgA or IgM antihistone antibodies, and IgA antihistone antibodies were
      the most common and reactive. Thirty-five percent of the patients had elevated
      levels of one or more immunoglobulin classes, and the IgA level was strongly
      correlated with IgA antihistone activity. These results suggest that isoniazid
      treatment results in modest increases in antihistone antibodies of the
      specificities and class typical of drug-induced autoimmunity in the absence of
      lupus-like disease. The IgA antihistone predominance suggests that serum
      antoantibodies may be the consequence of stimulation by isoniazid of lymphocytes
      in the gut-associated Peyer's patches or intestinal lymphoid follicles.

PMID- 7578867
TI  - Study of self reactive antibodies in kappa-light chain deficient mice.
AB  - The kappa chain deficient mouse strain represents an excellent experimental
      system for studying the contribution of lambda light chains to the antibody
      repertoire. Here, we have studied the contribution of lambda chains to the
      generation of self reactive antibodies including RFs in kappa deficient mice with
      129/sv background. These mutant mice produce rheumatoid factors similar to 129/sv
      mice and these antibodies are primarily encoded by lambda 2. This may be due to
      the production of RF by peritoneal B lymphocytes which belong to Ly1 B subset.
      Peritoneal B cell selectively produce lambda 2 and lambda 3 isotypes. Though
      lambda 1 positive RF is not detectable in the sera, lambda 1 positive specific
      precursor B cells are present in these mice and they can be activated by T
      independent antigens. Our studies show that these mice also spontaneously produce
      anti-dsDNA antibodies bearing lambda 1 light chain but do not produce self
      reactive antibodies specific for eight different autoantigens. However, B cell
      precursors expressing lambda chains specific for autoantigens like collagen II,
      III, IV and histone 2A are present in the B cell repertoire of kappa-deficient
      mice. Thus, our results demonstrate that lambda light chain can compensate, to
      some extent, the lack of kappa chain repertoire, not only against foreign
      antigens, as observed previously, but also against a number of autoantigens.

PMID- 7578868
TI  - Recipient-derived T cells participate in autoimmune-like hepatic lesions induced
      by graft-versus-host reaction.
AB  - Autoimmune-like hepatic lesions were induced by injection of CD4+ T cells from
      B10.Thy-1.1 mice into MHC class II-disparate (B10.Thy-1.1 x bm12)F1 mice. Hepatic
      lesions characterized by mononuclear cell accumulation in the portal area of the
      central vein and around interlobular bile ducts were observed in these
      recipients. The morphologic features of the lesions resembled primary biliary
      cirrhosis. The origin of T cells invading at the site of the hepatic lesions was
      immunohistochemically analyzed. It was shown that many recipient-derived T cells
      were present at the lesions and that some of them infiltrated the bile duct
      epithelia. Furthermore, the lesions were weakened when recipient-type T cells
      were depleted by thymectomy and the administration of anti-Thy-1.2 monoclonal
      antibody. Recipient-derived T cells were observed to take part in the formation
      of autoimmune hepatic lesions. These findings suggest the possibility that the
      tolerance of self-reactive T cells is abrogated by the graft-versus-host
      reaction.

PMID- 7578869
TI  - The CD5+ B cells and myasthenia gravis.
AB  - A high frequency of CD5+ B lymphocytes in the peripheral blood of patients with
      myasthenia gravis (MG) has been reported recently. These results seem to indicate
      an attractive linkage between CD5+ B lymphocytes and autoantibodies against
      Acetylcholine receptor in MG. We examined the frequency of CD5+ B cells in 20
      patients with MG and 21 normal healthy controls by two-color flow cytometry.
      However, there were no significant differences in the percentages of CD5+ B
      lymphocytes between the two groups. We also examined the frequency of CD5+ B
      lymphocytes in the resected thymus of patients. The frequency of CD5+ B
      lymphocytes in the thymus was low and similar pattern to that in the peripheral
      blood. We checked the antibody (Ab) production against the human acetylcholine
      receptor in either CD5+ B or CD5- B lymphocytes using B lymphoblastoid cell line
      generated from the lymphocytes of 11 patients with anti-AChR Abs in the sera. Abs
      against the AChR in the human were mostly produced by CD5- B, not CD5+ B
      lymphocytes. The anti-AChR Abs (IgG) production of CD5+ B cells and CD5- B cells
      (mean +/- SD) were 6.8 +/- 2.4 fmol/ml and 18.5 +/- 17.6 fmol/ml, respectively.
      These results suggest that in MG, the frequencies of the CD5+ B lymphocytes in
      PBL may be genetic background and that there may be no strong linages between
      AChR Ab production and CD5+ B lymphocytes.

PMID- 7578870
TI  - Evidence for a retroviral trigger in Graves' disease.
AB  - An apparently high frequency of Graves' disease encountered in New Orleans,
      Louisiana, prompted an investigation for a possible infectious agent that might
      be triggering the disease in genetically susceptible individuals. We studied 40
      patients with Graves' disease, and compared them to the following groups of
      controls: age and gender matched healthy subjects; patients with multinodular
      goiter (non-autoimmune thyroid controls); patients with chronic lymphocytic
      thyroiditis (autoimmune thyroid disease controls) and additional organ or tissue
      specific autoimmune controls exclusive of thyroid autoimmunity, including
      patients with Type I diabetes and other endocrine autoimmune complex disorders.
      Serum antibodies against a prototypic strain of a human intracisternal A-type
      retroviral particle type 1 (HIAP-1) were detected by a sensitive and specific
      immunoblotting assay. In 87.5% (35/40) of the Graves' disease patients there was
      a positive reaction against several HIAP-1-associated proteins, predominantly 97
      Kd and 80 Kd, with only 5 showing no reactivity to any. In contrast, 2% (2/105)
      of sera from normal controls showed positive reactivity. Furthermore, only 10%
      (1/10) of sera from multinodular goiter control patients and 10% (1/10) of
      Hashimoto's patients showed reactivity (p < 0.0005). Sera from 3 of 20 (15%) of
      Type I diabetic patients none of whom had Graves' disease, showed reactivity but
      there was no reactivity in 9 other patients with one or more of the endocrine
      autoimmune complex disorders, including Addison's disease, vitiligo, myasthenia
      gravis and pernicious anemia. In addition we studied two individuals with Graves'
      disease from each of two families residing outside Louisiana, all of whom were
      positive for these antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578871
TI  - Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in
      thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.
AB  - We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid
      tissues obtained from patients with autoimmune diseases or neoplastic thyroid
      disorders employing immunohistochemistry in sections from paraffin embedded
      tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells
      (TFEC) from papillary carcinomas (four of five patients) but not in follicular
      carcinomas (five patients). Interleukin-6 was also detected in non-toxic
      multinodular goiters (four of seven patients), in patients with Graves' disease
      who did not have an early recurrence of hyperthyroidism after surgery (three of
      four patients), in follicular adenomas (five of nine patients), in Hashimoto's
      thyroiditis (two out of six patients, both belonging to a group of three with an
      early stage of the disease), and in paraadenomatous tissues (in three of nine
      patients). Interleukin-1 alpha positive TFEC were found less frequently than
      interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few
      interleukin-6 and interleukin-1 alpha positive interstitial cells were found,
      even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant
      disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be
      demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or
      papillary carcinoma, whereas follicular cancer tissues were without interleukin-6
      and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and
      interleukin-1 alpha were demonstrated in TFEC from patients with both Graves'
      disease and Hashimoto's thyroiditis, and the presence of these cytokines was
      related to the stage of the autoimmune process.

PMID- 7578872
TI  - Low dose streptozotocin causes diabetes in severe combined immunodeficient (SCID)
      mice without immune cell infiltration of the pancreatic islets.
AB  - Streptozotocin (stz) given in low doses (40 mg/kg body weight) on 5 consecutive
      days to susceptible strains of mice causes diabetes. Previous studies have shown
      that the induction of diabetes is associated with inflammatory infiltrates within
      the pancreatic islets. However, it is unclear whether stz causes limited beta
      cell destruction followed by insulitis or whether the diabetogen promotes immune
      cell influx into the pancreatic islets, followed by immune-mediated beta-cell
      destruction. It is also unclear whether stz given in sub-diabetogenic doses is
      capable of causing diabetes independent of cell-mediated processes. Here we have
      examined these possibilities in CB.17 Scid mice which lack functional T and B
      cells but have immunocompetent macrophages and NK cells. Low dose stz given to
      Scid mice caused diabetes in approximately 50% of mice of both sexes by 21 days
      (14/24 males; 10/18 females). Sections of pancreas were examined
      immunohistochemically for the presence of MAC-1 positive cells (macrophages and
      natural killer cells) in the exocrine, peri- and intra-islet regions at different
      time points following the administration of stz. There were no statistically
      significant differences in the number of immunoreactive cells in the three
      locations between tissues obtained from stz-injected mice (3, 7, 14 and 21 days
      after stz injection and at onset of diabetes) and buffer-injected Scid mice.
      Although diabetic Scid mice showed a reduced number of insulin immunoreactive
      cells and peri- and intra-islet distributed glucagon cells, no insulitis was seen
      histochemically. In parallel studies, normal Swiss male mice given stz at a
      similar dose developed diabetes (10/10) associated with insulitis which consisted
      predominantly of CD4, CD8 and MAC-1 cells. Balb/c mice given stz similarly, also
      developed diabetes (5/8) without showing insulitis, although a moderate increase
      in the number of macrophages were observed within several islets. These studies
      demonstrate that stz administered in multiple low doses to Scid mice can cause
      beta cell destruction and diabetes in the absence of immune cell infiltrate
      within the pancreatic islets.

PMID- 7578873
TI  - Cytotoxicity towards neonatal versus adult BB rat pancreatic islet cells.
AB  - Cell-mediated autoimmunity is believed to influence the development of diabetes
      in BB rats. It has been suggested that the autoimmune destruction is due to lack
      of tolerance induction in early neonatal life caused by delayed maturation of the
      pancreatic beta cells. The present experiment has been initiated to investigate
      if there is any difference in in vitro cytotoxicity, and therefore antigenicity,
      to islet cells from neonatal, young and adult diabetes prone BB rats, and to
      establish the possible developmental difference in these rats compared to non
      diabetes prone Wistar Furth rats. Islets from rats of different ages were
      isolated, dispersed and 51C-labeled. In vitro cytotoxicity mediated by
      mononuclear spleen cells from newly diabetic BB rats was measured by counting
      gamma-ray emission from the culture supernatant after 16 h coincubation. We found
      that full adult-like islet cell maturation in BB rats--as evidenced by
      sensitivity to cytotoxicity--is not seen before the age of 8 to 21 days after
      birth. In contrast adult-like cytotoxicity to neonatal islets cells from Wistar
      Furth rats is seen already at the age of 8 days. Thus delayed islet cell
      maturation is a fact observed in BB rats.

PMID- 7578874
TI  - Titin antibodies in patients with late onset myasthenia gravis: clinical
      correlations.
AB  - We have tested sera from 21 thymectomized patients with onset of MG after 40
      years of age and without thymoma for antibodies against titin, using ELISA with
      the titin peptide MGT-30. Titin is a myofibrillar protein unique to striated
      muscle and important for the elastic recoil of muscle cells. Titin antibodies
      were detected in 9 of the 21 sera. MG symptoms as assessed by a 6 point
      disability score (0-5) were significantly more severe in the titin antibody
      positive patients both at peak of illness; 3.7 vs. 3.1 (p < 0.02) and at latest
      follow up; 2.1 vs. 0.8 (p < 0.01). All titin antibody positive patients were on
      immunosuppressive drug treatment at least follow-up, whereas only 3 of 12
      patients without titin antibodies used immunosuppressive drugs. The presence of
      circulating titin antibodies in late-onset non-thymoma MG patients indicates a
      more severe disease.

PMID- 7578875
TI  - Glycolipids as the major autoantigens of cytoplasmatic islet cell antibodies.
AB  - It has been recently suggested that pancreatic glycolipidic extracts and acidic
      glycolipid fractions are able to block the binding of ICA to frozen sections of
      human pancreas. We study the prevalence of blocking effect by the upper-phase
      from human pancreatic glycolipid extracts (PGE) in thirty-eight sera ICA positive
      from seventeen IDDM patients and twenty-one first relatives of type 1 diabetics.
      Total inhibition was found in 82% and 76% insulin dependent diabetes mellitus
      patients and first relatives of type 1 diabetics respectively. Partial and no
      inhibition of ICA+ sera was seen in 6%, 12% of type 1 diabetics and 19%, 5% of
      the first degree relatives of type 1 diabetics respectively. Our study suggests
      that there is heterogeneity of cytoplasmatic islet cell antibodies and that
      glycolipids are the major autoantigen of ICA.

PMID- 7578876
TI  - Type XI and II collagen-induced arthritis in rats: characterization of inbred
      strains of rats for arthritis-susceptibility and immune-responsiveness to type XI
      and II collagen.
AB  - To determine the relationship between susceptibility to bovine type XI and II
      (BXI and BII) collagen-induced arthritis, we immunized 14 inbred and one outbred
      strains of rats with BXI and BII. Susceptibility to BXI-arthritis corresponded
      largely with susceptibility, or resistance, to BII-arthritis. LEW, BB, WF, DA,
      and WKY were readily susceptible to BXI- and BII-arthritis. Likewise, BII
      resistant F344 and BN rats were BXI-resistant. Some strains responded differently
      to BXI and BII. BUF and COP, which are moderately susceptible to BII, were BXI
      resistant, whereas the BII-resistant rats, DA.1N and WF.1N, were partially
      susceptible to BXI. (F344 x BN) F1 hybrids responded to both collagens suggesting
      gene complementation. Arthritis occurred in all strains producing the highest
      titer antisera (LEW, WF and BB). Antibody responses to BXI and BII were generally
      commensurate within individual strains. DA were susceptible to arthritis but
      produced low levels of antibody comparable to BN rats which were arthritis
      resistant. BXI and BII-susceptibility was variable in rats producing intermediate
      antibody responses. Antibodies to RXI were detected in all BXI-immunized rats,
      whereas antibodies to RV and RII were uniformly weaker. DTH to RXI and RII was
      strong in both groups of rats, correlating poorly with arthritis and antibody
      responses. These studies show that phenotypic susceptibility to BXI- and BII
      arthritis are largely concordant among inbred rat strains but clear differences
      exist in certain strains; multiple genes are likely involved.

PMID- 7578878
TI  - Molecular characterization of monoclonal IgM derived from human B cell lines
      expressing the 4C9 rheumatoid factor associated idiotype.
AB  - Ten human monoclonal B cell lines that express the RF associated Id 4C9 were
      analyzed using an immunogenetic approach. Five of eight tested lines were also
      strongly positive for the 6B6.6 Id. We found that all the 4C9/6B6.6 positive
      lines expressed VkIIIa light chain genes. In contrast, 4C9 reactivity was also
      found on a cell line expressing a VkIIIb light chain gene and on a line
      expressing a V light chain gene. The two anti-Ids recognized a linear light chain
      determinant on Humkv328 encoded light chains but also a conformational
      determinant on Vg encoded light chains that appeared to be dependent on the
      presence of a heavy chain. Idiotypic reactivity occurred on both RF positive and
      RF negative antibodies. Within this idiotypic system, the basis for idiotypic
      reactivity and RF reactivity is complex, subject to both heavy and light chain
      gene usage and sensitive to small numbers of somatic mutations.

PMID- 7578877
TI  - Restricted expression of T cell receptor V beta and lymphokine genes in arthritic
      joints of a TCR V beta a (H-2q) mouse strain-BUB/BnJ-with collagen-induced
      arthritis.
AB  - Type II collagen-induced arthritis (CIA) is an animal model of inflammatory
      polyarthritis with clinical and pathological features resembling rheumatoid
      arthritis (RA). We compared the expression of T cell receptor (TCR) V beta genes
      in T cells isolated from the inflamed joints, draining lymph nodes and the
      spleens of BUB/BnJ (H-2q) mice (BUB) during the early phase of CIA. We also
      investigated the profiles of cytokine gene expression in T cells obtained from
      the same tissues. We found that the expression of TCR V beta s, in arthritic
      joints of mice, during the early phase of the disease was limited to TCR V beta 3
      and 10 gene families. In contrast, TCR V beta 4, 7, and 15 were predominant in
      the draining lymph nodes (LNs) and TCR V beta 2, 6, and 14 were predominant in
      the spleens of arthritic mice. Molecular cloning and sequence analysis revealed
      that the T cell populations in the arthritic joints were oligoclonal as
      determined by the limited N-D-N region diversity observed in the sequenced
      clones. These results demonstrate, for the first time, that (1) joint
      infiltrating T cells in TCR V beta a genotype mice use a restricted repertoire of
      TCR V beta genes; (2) there was oligoclonal expansion of infiltrating T cells in
      arthritic joints in mice with collagen-induced arthritis. Our results on cytokine
      gene expression in the arthritic joints of BUB mice indicate that Th-1-like T
      cell derived cytokines may be the predominant cytokines in the arthritic joints
      as illustrated by the presence of transcripts for IL-2 and IFN-gamma but not IL
      4. In summary, our results provide evidence that T cells with restricted
      specificities, and more specificially, Th-1 type T cells, are crucial in the
      early phase of collagen induced arthritis in mice.

PMID- 7578879
TI  - Effects of prolonged exposure in vitro to interferon-gamma and tumour necrosis
      factor-alpha on nitric oxide and insulin production of rat pancreatic islets.
AB  - It has been postulated that cytokines may mediate the beta-cell destructive
      process causing insulin-dependent diabetes mellitus. The aim of this
      investigation was to study cytokine effects on pancreatic islet functions in
      vitro. For this purpose 5-7 days precultured (medium RPMI 1640 +/- 10% fetal calf
      serum) rat pancreatic islets were exposed for another 48 h to either culture
      medium alone or with addition of rat interferon-gamma (IFN-gamma; 1000 U/ml), or
      human tumor necrosis factor-alpha (TNF-alpha; 1000 U/ml) or a combination of the
      cytokines. After the culture period the islets were subjected to short-term
      experiments in the absence of cytokines. Neither the DNA nor the insulin content
      of the islets were affected by the cytokines alone or by the combination. The
      combination IFN-gamma + TNF-alpha caused a 5-fold increase in the medium nitrite
      accumulation, indicating induction of nitric oxide formation. It was found that
      IFN-gamma reduced medium insulin accumulation and basal insulin secretion at 1.7
      mM glucose, without affecting the medium nitrite level. On the other hand, the
      islet glucose oxidation rate at 16.7 mM glucose and the insulin secretory
      response to 16.7 mM glucose was normal or even increased when examined after 48
      h. TNF-alpha alone had no significant effects. In conclusion, a combination of
      the cytokines can induce nitric oxide formation and inhibition of insulin
      production in rat pancreatic islets. However, this effect appears not to be
      sustained. Moreover, IFN-gamma alone seems to induce changes not related to
      nitric oxide.

PMID- 7578880
TI  - A subgroup of human VH3 germline genes that encode a high-avidity synovial
      rheumatoid factor.
AB  - We have previously derived and identified a highly avid monoclonal IgM rheumatoid
      factor (mRF), C6, from unstimulated rheumatoid synovial cells (RSC). At the time,
      the closet VH germline gene, VH26, demonstrated only 88% homology with C6. To
      identify the germline counterpart of C6, genomic DNA from the same rheumatoid
      arthritis (RA) patient from whom C6 was derived was used in the polymerase chain
      reaction (PCR). Four of the six closely related germline genes that we sequenced
      had exonic regions that were identical with the VH region of C6 cDNA. These six
      germline sequences differed in their intronic regions, suggesting that they were
      distinct, but closely related genomic sequences. To further evaluate the extent
      of these related genes we identified nine additional germline genes having VH
      encoding exons that were 86-97% identical to the C6 cDNA sequence. Furthermore,
      we examined the polymorphic nature of the C6 VH gene using single strand
      conformation polymorphism (SSCP), and identified two peaks, confirming the
      existence of highly homologous genes. The sequence and polymorphism data suggest
      that: (1) the VH region of the high avidity mRF C6 was derived from an unmutated
      germline gene; (2) C6 was encoded by a VH gene belonging to a set of homologous
      genes within the larger VH3 family; and (3) in addition to somatic rearrangements
      of B-cell genes and antigen-driven somatic mutation, gene duplication and
      conversion events of germline genes could be important in generating diversity
      and polyclonality among high-affinity pathogenic autoantibodies.

PMID- 7578881
TI  - Excess iodine induces the expression of thyroid solid cell nests in lymphocytic
      thyroiditis-prone BB/W rats.
AB  - Previous epidemiological studies have suggested that lymphocytic thyroiditis
      and/or an increased iodine intake may be risk factors for the development of
      thyroid cancer. We previously reported that excess iodine accelerated the
      development of thyroid lymphocytic infiltration (LI) in the autoimmune BB/W rat
      model. We also found that excess iodine increased thyroid cell proliferation in a
      disordered manner. The present study was designed to further explore these
      observations and to address the question as to whether excess iodine under
      certain conditions predisposes the thyroid gland to neoplasia. To test this
      hypothesis, the lymphocytic thyroiditis-prone BB/W rat was exposed to excess
      iodine in drinking water. Ten BB/W rats at 4 weeks of age were given iodine water
      (NaI 0.05%) for 10 weeks, whilst another 10 BB/W rats were given tap water and
      served as controls. Eighteen normal Wistar rats were also divided into excess
      iodine and control groups, served as a comparison to the BB/W rats. We found that
      an excess iodine intake accelerated the development of LI in the BB/W rat. Severe
      LI was usually accompanied by prominent thyroid cell proliferation, evident as
      numerous microfollicles and cell masses, not forming normal thyroid follicles.
      Numerous lymphocytes and plasma cells often encroached on these areas of
      increased cellular proliferation. The surprising feature, and a possible
      indicator of activated thyroid cell proliferation, was the high incidence of
      thyroid solid cell nest-like lesions (SCN) in the iodine treated BB/W
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578882
TI  - A novel concept of type VII hypersensitivity introduced by insulin autoimmune
      syndrome (Hirata's disease)

PMID- 7578883
TI  - Target antigen(s) in endometrial autoimmunity of endometriosis.
AB  - OBJECTIVE: To obtain the molecular weights (MW) of endometrial antigens eliciting
      immunoglobulin (Ig) G auto-antibodies in all endometriosis patients irrespective
      of their place of origin or race, and to verify their specificity and
      immunogenicity. STUDY DESIGN AND RESULTS: We tested the serum and peritoneal
      fluid (P.F.) of 76 endometriosis patients and 24 controls from 4 cities against
      endometrial and implant antigens by Western blot analysis. Endometrial and
      implant antigens with MW of 34, 46/48, 64, 84, 94 and 120 kDa bound with IgG in
      serum and PF of most patients, but not the controls. Antigen(s) with MW of 64 kDa
      was reactive against serum or P.F. IgG of patients from all cities. Specificity:
      Endometrial and implant extracts did not react with monoclonal antibodies to WBC
      subsets and 5 sera with nuclear antibodies. Also, the presence of nuclear and
      endometrial antibodies did not correlate in 20 other patients with endometriosis.
      Immunogenicity: We immunized rabbits with the native and eluted (MW 29 to 68 kDa
      and > or = 68 kDa) endometrial and implant proteins. The antiserum had specific
      IgG binding to the same glandular epithelial antigens as those bound by the
      patient's serum. CONCLUSIONS: Endometrial antigens with MW of 34, 46/48, 64, 94
      and 120 kDa, especially 64 kDa appear to be specific, immunogenic and relevant to
      endometrial autoimmunity in all patients with endometriosis.

PMID- 7578884
TI  - Cytokine gene and CD25 antigen expression by peripheral blood T cells from
      patients with primary Sjogren's syndrome.
AB  - We studied mononuclear cell subsets in 17 patients with primary Sjogren's
      syndrome (PSS) and in 11 normal controls by flow cytometry. We found a decreased
      percentage of CD4+ cells (p = 0.027) and a higher percentage of CD8+ cells in
      patients as compared to controls. In both, CD4+ cells and CD8+ cells, CD25
      antigen was overexpressed (p = 0.005 and p = 0.025, respectively as compared to
      controls). We then measured spontaneous mRNA cytokine expression by T cells from
      7 PSS patients and 5 normal controls by coupled reverse transcription-polymerase
      chain reaction. We found spontaneous mRNA expression for IFN-gamma, IL-10, IL-13
      as well as for CD25. Our results suggest an overall T cell activation in PSS
      patients and provides evidence of a T cell cytokine regulatory imbalance which
      may play a role in the pathogenesis of this disease.

PMID- 7578885
TI  - Apoptosis in thyroid tissue from patients with Hashimoto's thyroiditis.
AB  - To clarify whether apoptosis of thyroid follicular epithelial cells occurs at the
      tissue level in autoimmune thyroiditis, 17 specimens of thyroid tissues with
      Hashimoto's thyroiditis were stained for fragmented DNA. Almost all nuclei of
      follicular epithelial cells forming atrophic thyroid follicles surrounded by
      mononuclear cell infiltration and fibrosis showed positive staining. With
      increasing distance from lymphoid cell follicles, the percentage of follicular
      epithelial cells with DNA fragmentation-positive nuclei decreased (30-80%).
      Electron microscopic study revealed the existence of epithelial cells with shrunk
      and condensed nuclei. The frequency of those cells in different areas was almost
      compatible with that of cells with fragmentation-positive nuclei. These findings
      suggest that apoptosis plays an important role in the thyroid tissue injury in
      autoimmune thyroiditis.

PMID- 7578886
TI  - Characterization of a novel human IgG antibody reactive with a Ca(2+)-sensitive
      cell-cell adhesion epitope of PtK2 epithelial cells.
AB  - We have characterized a human IgG antibody present in the serum of a patient with
      an autoimmune undifferentiated connective tissue disease and reactive with PtK2
      epithelial cell-cell adhesions. The fluorescent staining pattern is observed only
      at cell-cell contacts whether cells are permeabilized or not. The serum reacts
      with polypeptides of 90, 48 and 45 kD by immunoblotting. IgG affinity-purified
      from these bands failed to reproduce the original immunofluorescence staining
      pattern. Treatment with cycloheximide did not abolish the staining pattern
      suggesting that the recognized antigen is not a newly expressed protein. However,
      when EGTA was used for chelating calcium ions in the culture medium the original
      staining pattern observed at cell-cell adhesions was affected although some
      fluorescence was still present at cell periphery. This was reversible when cells
      were reincubated with fresh medium containing Ca2+. The recognized antigen
      colocalizes at cell-cell adhesions with actin, the microfilament-associated
      proteins vinculin, alpha-actinin and myosin light chain, and with Triton
      insoluble uvomorulin (E-cadherin) material. We conclude that the antibody reacts
      with, at least, an extracellular portion of a Ca(2+)-dependent PtK2 antigen. The
      characterization of this antibody based on (1) its localization at cell-cell
      adhesions, (2) its sensitivity to EGTA-treatment and (3) its colocalization with
      the epithelial cellular adhesion molecule (CAM) uvomorulin, strongly suggest that
      the recognized Ag is a CAM or a CAM-associated protein.

PMID- 7578887
TI  - Association of an androgen-responsive T cell phenotype with murine diabetes and
      Idd2.
AB  - T cells are involved in the induction and suppression of autoimmune diabetes in
      nonobese diabetic (NOD) mice. Because the incidence of diabetes is 13-fold
      greater in NOD/Smrf females, we searched for T cell phenotypes that showed sexual
      dimorphism and associated with diabetes in backcross segregants. The percentage
      of CD4+PBL was higher in NOD/Smrf females than males, was intermediate in [NOD X
      NON] F1 mice and approximated a 1:1 distribution in F1 mice backcrossed to either
      NOD or NON parental strains, suggesting primary control of the phenotype by an
      incompletely dominant gene, but not excluding additional effects by other genes.
      We term this primary gene Tlf(T lymphocyte frequency) because it also influenced
      the percentage of CD8+ T cells, although to lesser extent and independently from
      the MHC previously shown to lower the CD8+ T cell fraction in NON mice. Tlf
      segregated with diabetes in BC1 females, suggesting linkage with at least one
      diabetic locus. Genotyping of markers for Idd1, Idd2, and Idd3/10 revealed that
      Tlf mapped with Idd2 on chromosome 9. Dihydrotestosterone simultaneously lowered
      CD4+ PBL levels and prevented diabetes in NOD females while, in vitro, it had a
      differential effect on Con A elicited cytokines, increasing IL-2 22% and
      decreasing IL-4 39% (p < 0.0001). Thus the Tlf phenotype in NOD females, like
      diabetes, can be modulated by androgens.

PMID- 7578888
TI  - Analysis of the V kappa I family: germline genes from an SLE patient and
      expressed autoantibodies.
AB  - Our studies of anti-DNA antibodies in systemic lupus erythematosus have
      demonstrated a preferential use of the V kappa I family to encode light chains of
      antibodies that express the anti-DNA associated 3I idiotype. This idiotype is
      present on a high percentage of anti-DNA antibodies in approximately 80% of SLE
      patients1,2. In this study, we employed PCR to obtain V kappa I germline genes
      from a lupus patient in order to address the following questions: Do the V kappa
      I germline genes of an individual with autoimmune disease differ from those of
      healthy individuals? What V kappa I genes are used to encode autoantibodies and
      are they used to encode protective antibodies also? Does the V kappa I gene
      family display peculiarities in V gene segment rearrangement or somatic mutation?
      Our analysis shows that the coding region sequences of germline genes of an
      autoimmune individual are highly homologous to those of non-autoimmune
      individuals. In addition, the same germline genes can be utilized to encode
      antibodies to both exogenous and self antigens. While rearranged V kappa genes
      are ordinarily derived from the J kappa proximal region of the V kappa locus, V
      kappa I genes encoding autoantibodies derive primarily from the J kappa distal
      region. It is not yet clear if this applies equally to V kappa I encoded
      antibodies directed to foreign antigen.

PMID- 7578890
TI  - Risk factors for cerebrovascular disease and the role of coagulation and
      fibrinolysis.
AB  - Cerebrovascular disease is one of the major causes of morbidity and mortality in
      the developed world. A number of important risk factors have been identified with
      the occurrence of stroke, including advancing age, hypertension, smoking and
      diabetes mellitus, but the mechanisms that link these risk factors to the
      development of cerebrovascular disease are unclear. The pathogenesis of
      cerebrovascular disease includes syndromes of atherothrombotic brain infarction
      and intracerebral hemorrhage. The role of abnormalities of the coagulation and
      fibrinolytic systems in these processes has not been properly evaluated with
      regard to clinical outcome, although there is evidence that raised concentrations
      of fibrinogen are associated with an increased risk of stroke. Smaller studies
      have identified increases in FVIII/vWF in association with acute stroke and
      raised levels of tissue plasminogen activator. Although factor VII is considered
      a risk factor for coronary artery disease, little is known regarding its role in
      the development of cerebrovascular disease. Improved understanding of the
      pathogenesis of stroke and the potential to predict patients at risk of stroke
      should herald the beginning of new approaches in stroke management.

PMID- 7578889
TI  - Increased natural autoantibody activity to cytoskeleton proteins in sera from
      patients with necrobiosis lipoidica, with or without insulin-dependent diabetes
      mellitus.
AB  - Necrobiosis lipoidica (NL), a skin disease, is associated with insulin-dependent
      diabetes mellitus (IDDM). Natural autoantibody (NAb) activity in sera from 16
      patients suffering from NL, with or without IDDM, was compared to that in sera
      from 41 patients with IDDM and 43 healthy controls. Isotype-specific enzyme
      linked immunosorbent assays (ELISAs) were used to detect NAbs against actin,
      myosin, keratin, desmin, troponin, tropomyosin, thyroglobulin, insulin, single
      stranded DNA and the hapten trinitrophenyl. NAb activity was significantly higher
      in sera from patients with NL (either with or without IDDM), compared with that
      detected in sera from patients with IDDM which was similar to that of healthy
      individuals. High proportion of NL sera exhibited increased IgG anti-tropomyosin
      (69%), anti-troponin, anti-desmin and anti-keratin (50% each), anti-insulin (44%)
      and anti-trinitrophenyl (31%) activities, as well as increased IgA and IgM anti
      keratin activities (26% and 31%, respectively). The great majority (88%) of
      positive sera were polyreactive and contained NAbs, polyspecific and monospecific
      (as demonstrated by immunoadsorption studies), belonging to more than one
      isotype; there was no predominant serological reactivity pattern. In conclusion,
      increased NAb activity to cytoskeleton proteins is associated with the
      dermatological disease NL and not to the overlapping autoimmune disease (IDDM).
      The origin and significance of these NAbs is discussed.

PMID- 7578891
TI  - Challenges in the development of orally bioavailable thrombin active site
      inhibitors.
AB  - Activated thrombin plays a central role thrombosis and in hemostasis, both by
      controlling the coagulation process, and by activating receptors on platelets and
      various cell types. A safe and effective inhibitor of thrombin active site could
      be a useful tool in the treatment of venous thrombosis, atrial fibrillation,
      restenosis, arterial thrombosis, and in the prevention of myocardial infarction.
      Because of this, the modulation of thrombin by direct, small molecule inhibitors
      is a widely sought goal in the pharmaceutical industry. However, this search has
      thus far proved elusive. Criteria for a pharmaceutically acceptable thrombin
      inhibitor include high and reproducible bioavailability, selectivity, and a long
      duration of action. The profile of currently researched thrombin active site
      inhibitors is discussed in relation to these goals.

PMID- 7578892
TI  - An enzyme immunoassay for the simultaneous determination of active type-1
      plasminogen activator inhibitor (PAI-1), and t-PA/PAI-1 complexes.
AB  - An assay has been developed which enables the simultaneous determination of
      active free PAI-1 and t-PA/PAI-1 complexes in plasma samples. Test plasma is
      divided into two subsamples in which (a) active PAI-1 is quantitatively converted
      to t-PA/PAI-1 complexes, and (b) conversion of PAI-1 to t-PA/PAI-1 complexes is
      prevented. The amounts of t-PA/PAI-1 complex in the two subsamples are then
      assessed in a one-step enzyme immunoassay (EIA) consisting of a monoclonal anti
      PA antibody, and a HRP conjugate of polyclonal anti-PAI-1 antibodies. The amounts
      of t-PA/PAI-1 complexes in the two subsamples are the t-PA/PAI-1 complex
      concentrations at the time of sampling (b); whereas the difference between the
      two values (a)-(b) equals the amount of active PAI-1. The assay has a high
      sensitivity, specificity, accuracy and precision. The time-to-result is 4.5 h. It
      meets the criteria set by the Scientific and Standardization Committee (SSC) of
      the International Society of Thrombosis and Haemostasis (ISTH) for a candidate
      reference method.

PMID- 7578893
TI  - Influence of heparin thromboprophylaxis on plasma leucocyte elastase levels
      following lobectomy for lung carcinoma.
AB  - Recent in vitro studies and animal investigation indicate that plasma leucocyte
      elastase (PLE) can dissolve pulmonary structural proteins, such as elastin, and
      produce lesions in the lung similar to that seen in adult respiratory distress
      syndrome (ARDS) and emphysema. In contrast, heparin strongly inhibits PLE and
      protects elastin from elastolysis. On the basis of these findings, PLE levels
      were monitored in 24 patients with non-small cell lung carcinoma (NSCLC)
      undergoing lobectomy. Ten patients from Killingbeck Hospital (Group 1) received
      5000 IU subcutaneous (s.c.) heparin commenced 2 h prior to surgery and continued
      at 8 h intervals until the patient was fully ambulatory. Fourteen patients from
      Bradford Royal Infirmary (Group 2) received no heparin as standard policy. There
      was no significant difference in pre-operative PLE levels between groups. The
      post operative PLE levels in both groups increased significantly (P < 0.02) on
      the first post operation day (POD). However, PLE levels of Group 2 were 2.5 to
      5.3 times higher than those of Group 1 at each postoperative interval (first,
      third, and seventh POD) respectively (0.002 < P < 0.02). There was no difference
      in blood loss between groups (P = 0.17). These results indicate that post
      operative PLE activity is elevated in NSCLC patients following lobectomy and s.c.
      heparin administration as thromboprophylaxis may inhibit PLE activity post
      operatively without increasing blood loss. Therefore, heparin may have a role to
      play in protecting lung tissue against the pulmonary lesions caused by
      proteolytic activity of PLE, and theoretically reduce post-operative
      complications, such as ARDS or emphysema.

PMID- 7578894
TI  - Ectopic transcript analysis in human antithrombin deficiency.
AB  - Reverse transcription and amplification of total cellular RNA isolated from
      peripheral blood mononuclear cells has been used to identify correctly spliced
      transcripts for human antithrombin. We have explored the potential of this
      technique for identifying the underlying mutation in five individuals with a Type
      I deficiency and one individual with a Type II deficiency. In each case correctly
      spliced transcripts of the correct size were obtained, direct sequencing of which
      clearly demonstrated the mutation. This method simplifies the detection of
      mutations in cases of antithrombin deficiency and further extends the use of
      ectopic transcript analysis.

PMID- 7578895
TI  - Ethnic variations in the haemostatic system: comparison between Arabs, Westerners
      (Europeans and Americans), Asians and Africans.
AB  - A wide variety of haemostatic variables were measured in healthy male subjects
      predominantly blood donors residing in Riyadh, the capital city of Saudi Arabia.
      Subjects were divided according to ethnic origin: Saudi Arabs n = 487, Westerners
      (Europeans and Americans) n = 300, South East Asians (Koreans and Filipinos) n =
      360, and West Africans n = 82. There were no significant differences in
      prothrombin time, partial thromboplastin time, thrombin time, reptilase time,
      plasma fibrinogen, antithrombin, plasminogen and platelet count between Saudis,
      Westerners and Asians. Africans exhibited significantly lower plasma levels of
      fibrinogen, platelet count and plasminogen than other ethnic groups. Arabs and
      Africans had higher levels of FVIII:C and vWF:ristocetin cofactor than
      Westerners. On the other hand, FX was significantly higher in Westerners than in
      other ethnic groups. Smokers had higher fibrinogen levels than non-smokers. These
      variations, which could not be related to blood group distribution, physical
      parameters of height and weight, may be due to genetic and/or dietary habits. In
      conclusion, this study established the existence of racially determined
      variations in haemostatic variables, with Black Africans showing changes
      consistent with a lesser tendency towards atherosclerosis and cardiovascular
      disease than other ethnic groups. These variations should be taken into account
      when investigating the haemostatic system in patients.

PMID- 7578896
TI  - Improvement of fibrinolysis and plasma lipoprotein levels induced by gemfibrozil
      in hypertriglyceridemia.
AB  - A randomized double-blind study was carried out with gemfibrozil (600 mg b.i.d.)
      vs placebo in 20 patients (twelve males and eight females, age 52 +/- 3 years,
      BMI 24.2 +/- 0.4) suffering from primary hypertriglyceridemia (Fredrickson's type
      IV). Each group was treated for a 12 week period with gemfibrozil (n = 10) or
      placebo (n = 10) patients) in a double-blind fashion. Total cholesterol, HDL
      cholesterol (HDL-C) and its subfractions (HDL2-C and HDL3-C), blood glucose,
      Apolipoproteins A1 and B, fibrinogen, plasminogen, factor VII, t-PA:Ag and PAI
      activity pre- and post-venous occlusion (VO) were determined. In the gemfibrozil
      treated group a significant decrease of total cholesterol and triglycerides and a
      significant increase of HDL-C and HDL2-C were found. During gemfibrozil treatment
      a significant reduction of factor VII, fibrinogen and plasminogen levels was also
      observed. After 12 weeks of treatment in the gemfibrozil group the release of t
      PA:Ag in response to venous occlusion was significantly higher and plasma PAI
      activity was significantly lower than in placebo group. Moreover positive
      correlations between HDL cholesterol and t-PA:Ag post-VO (r = 0.56, P < 0.01) and
      between HDL2-C cholesterol and t-PA:Ag post-VO (r = 0.59, P < 0.01) and a
      negative correlation between triglycerides and t-PA:Ag post-VO (r = -0.65, P <
      0.01) were found. The data obtained suggest that gemfibrozil, in addition to the
      well established lipid-regulating effect, appears to have a positive role in the
      regulation of reverse cholesterol transport and fibrinolytic system.

PMID- 7578897
TI  - Severe hypofibrinogenemia associated with bilateral ischemic necrosis of toes and
      fingers.
AB  - Severe hypofibrinogenemia was found in an Algerian woman who, since the age of 37
      years, suffered three different episodes of ischemic necrosis of the toes and
      fingers leading to amputation of the toes and surgical removal of necrotic tissue
      (necretomy). No anti-fibrinogen antibody was present. The deficiency appeared to
      be due to severe congenital hypofibrinogenemia since the fibrinogen level
      remained at the same low level over a long period, without any abnormality of
      other coagulation proteins. The thrombotic events may be explained by the
      increased thrombin generation observed in the patient's plasma, due to the lack
      of thrombin adsorption onto a fibrin net.

PMID- 7578898
TI  - Inhibition of extrinsic and intrinsic thrombin generation by a novel synthetic
      thrombin inhibitor (Ro 46-6240), recombinant hirudin and heparin in human plasma.
AB  - To further define the anticoagulant activity of Ro 46-6240, a novel, synthetic,
      thrombin inhibitor, we compared its effect on extrinsic and intrinsic thrombin
      generation in human platelet-poor plasma with that of recombinant hirudin and
      standard heparin. The time course of thrombin generation was followed with a
      chromogenic substrate assay. The total amount of active thrombin formed was
      quantified by calculating the area under the thrombin generation curve. Ro 46
      6240 and r-hirudin delayed thrombin formation in a concentration-dependent manner
      in both activation systems whereas heparin showed this effect only in the
      intrinsic system. Heparin was the most potent inhibitor of extrinsic and
      intrinsic thrombin generation with IC50 values of 20 and 27 nM, respectively. Ro
      46-6240 was nearly as potent as r-hirudin for inhibiting extrinsic thrombin
      generation (IC50 418 vs 229 nM) and intrinsic thrombin generation (IC50 463 vs
      343 nM) despite a much lower affinity of Ro 46-6240 for thrombin (Ki apparent:
      0.3 nM) in a purified buffer system. The similar potency of the small active-site
      thrombin inhibitor compared to the larger hirudin may be explained by different
      kinetic mechanisms for inhibition of thrombin and by a higher accessibility to
      the phospholipid surface where thrombin generation takes place. In conclusion,
      our results show that a specific small thrombin inhibitor efficiently inhibits
      and delays thrombin generation in human coagulating plasma. This reduced thrombin
      generation might be caused by inhibition of thrombin-mediated feedback reactions
      during blood coagulation.

PMID- 7578900
TI  - Effect of fibrin structure on plasmin-mediated dissolution of plasma clots.
AB  - Previous studies in purified systems have demonstrated that fibrin structure
      influences the rate of conversion of plasminogen to plasmin by t-PA as well as
      the rate of plasmin-mediated clot digestion. The present study extended these
      observations to a plasma system in which fibrin structure was altered by varying
      the thrombin concentration, varying the plasma ionic strength, or by adding
      dextran 40. The effect of fibrin structure on the rate of fibrinolysis was
      assessed by adding plasminogen activators (t-PA or urokinase (UK)) either before
      or after clot formation. Gel formation and dissolution were monitored optically
      (turbidity) and isotopically (125I-fibrinogen). Clots formed under conditions of
      high ionic strength and/or high thrombin concentration were composed of thin
      fibrin fibres that dissolved slowly. Clots formed at lower ionic strengths, at
      lower thrombin concentrations or in the presence of dextran were composed of
      thicker fibres and dissolved more rapidly. The difference in fibrinolytic rate
      between thin and thick fibres was noted when t-PA or UK was added before or after
      clot formation. These data indicate that even in a plasma milieu fibre diameter
      is a factor in determining fibrinolytic rate induced by either UK or t-PA. The
      method by which fibre diameter is altered does not influence the conclusion that
      fibrinolytic rate is increased with increasing diameter.

PMID- 7578901
TI  - Demonstration that venous occlusion fails to release von Willebrand factor
      multimers.
AB  - The acute simultaneous release of tissue plasminogen activator (t-PA) and von
      Willebrand factor (vWF) from endothelial cells in response to a variety of
      agonists including thrombin, DDAVP, histamine and adrenalin has been described.
      In the present study we investigated the effect of venous occlusion on the
      circulating levels of t-PA and vWF, as well as the molecular organization of vWF
      in 20 normal subjects. After occlusion a significant increase in plasma t-PA
      levels was observed even after the values were corrected for haemoconcentration.
      Venous occlusion also enhanced plasma vWF values, but the increase was abolished
      when the correction for haemoconcentration was introduced. Following venous
      occlusion, no circulating abnormally large vWF multimers were detected in the
      subjects studied. These forms are normally not present in the circulation and are
      released from endothelial cells through the regulated vWF pathway; their absence
      therefore seems to demonstrate that this pathway is not activated after venous
      occlusion. Since occlusion does not enhance vWF synthesis, the increase in vWF
      observed in the subjects investigated may be fully attributed to
      haemoconcentration.

PMID- 7578902
TI  - Differential effects of staphylokinase, streptokinase and tissue-type plasminogen
      activator on the lysis of retracted human plasma clots and fibrinolytic plasma
      parameters in vitro.
AB  - A novel plasma clot lysis system was used to compare the fibrinolytic
      characteristics of staphylokinase, streptokinase and tissue-type plasminogen
      activator. 125I-fibrinogen-labelled human plasma clots were formed on needles and
      mechanically compressed after spontaneous retraction. This model is relatively
      resistant to lysis and differentiates between fibrin-specific and non-fibrin
      specific plasminogen activators. The novel plasminogen activator, recombinant
      staphylokinase, produced high rates of clot lysis without markedly influencing
      fibrinogen, plasminogen and alpha 2-antiplasmin in the plasma containing the
      clots. At equimolar concentrations, streptokinase markedly depleted these
      parameters in plasma despite low clot lysis rates. Tissue-type plasminogen
      activator showed relatively high lysis rates at low concentrations, but at higher
      concentrations, plasminogen depletion caused a decrease in clot lysis.
      Staphylokinase can be characterised as a fibrin-specific and plasminogen-saving
      fibrinolytic agent with a high clot lysis potential.

PMID- 7578899
TI  - Acquired von Willebrand disease associated with multiple myeloma;
      characterization of an inhibitor to von Willebrand factor.
AB  - Acquired von Willebrand disease (vWD) has been described in a few patients with
      multiple myeloma. The present study characterizes an inhibitor of von Willebrand
      factor (vWF) isolated from a patient with multiple myeloma (IgG-kappa).
      Multimeric analysis of vWF from this patient's plasma showed a reduction in
      multimers of all sizes. The inhibitor (IgG) detected only the vWF subunit from
      plasma of normal individuals. It reacted with intact vWF subunit and a 39/34kDa
      dispase-digested fragment of vWF (residues; Leu480/Val481-Gly718), but did not
      react with platelet membrane glycoproteins (GPs) or adhesive proteins. The
      binding of vWF to GPIb mediated by ristocetin and by botrocetin was inhibited by
      the patient's IgG with an IC50s of 0.3 mg/ml and 0.48 mg/ml, respectively. The
      platelet aggregation induced by ristocetin or botrocetin was also inhibited by
      the IgG. These results indicate that this inhibitor may recognize the binding
      region of vWF to GPIb. Therefore, the antibody to vWF appears to represent the
      likely pathophysiological mechanism responsible for the acquired vWD in this
      patient.

PMID- 7578903
TI  - Sequences of actin implicated in the polymerization process: a simplified
      mathematical approach to probe the role of these segments.
AB  - Regulation of actin polymerization and depolymerization is essential for the
      functions of actin in non-muscle cells and is mediated by a large number of
      heterologous actin-binding proteins which questions their true impact on the
      polymerization process. As a model, we report here the modulating effect of
      monospecific antibody fragments (Fab) as in vitro effectors on actin
      polymerization kinetics. Polymerization curves were obtained through fluorescence
      measurements. They were fitted using analytical equations derived from classical
      models describing the actin polymerization process with the aim of identifying
      kinetic steps potentially altered by the effectors. The study was limited to
      three short segments bore by the 300-328 sequence which is located in actin
      subdomain 3 and implicated in one of the monomer-monomer interfaces. We observed
      that antibodies which inhibited actin polymerization reacted with both G- and F
      actins, modulated both nucleation and elongation steps, enhanced actin monomer
      dissociation from the filament and apparently did not act as capping or
      sequestering proteins. Among the antibody populations specific for a restricted
      and selected sequence in subdomain 3 of actin (sequence 300-326), only those
      directed to epitopes located near Met 305 and 325 were effective. In contrast,
      antibodies directed towards the alpha-helix located between the two preceding
      epitopes had no effect. All the results analyzed here emphasize the important
      role of some discrete regions and their conformational state in regulation of the
      interconversion between monomeric and polymeric actins which could be controlled
      in different ways by the various actin-binding proteins.

PMID- 7578905
TI  - Conformational studies of the (+)-trans, (-)-trans, (+)-cis, and (-)-cis adducts
      of anti-benzo[a]pyrene diolepoxide to N2-dG in duplex oligonucleotides using
      polyacrylamide gel electrophoresis and low-temperature fluorescence spectroscopy.
AB  - Using polyacrylamide gel electrophoresis (PAGE) and low-temperature, laser
      induced fluorescence line narrowing (FLN) and non-line narrowing (NLN)
      spectroscopic methods, the conformational characteristics of stereochemically
      defined and site-specific adducts derived from the binding of 7 beta,8 alpha
      dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (anti-BPDE, a
      metabolite of the environmental carcinogen benzo[a]pyrene), to DNA were studied.
      The focus of these studies was on the four stereochemically distinct anti-BPDE
      modified duplexes 5'-d(CCATCGCTACC).(GGTAGCGATGG), where G denotes the lesion
      site derived from trans or cis addition of the exocyclic amino group of guanine
      to the C10 position of either (+) or (-)-anti-BPDE. PAGE experiments under non
      denaturing conditions showed that the (+)-trans adduct causes a significantly
      greater retardation in the electrophoretic mobility than the other three adducts,
      probably the result of important adduct-induced distortions of the duplex
      structure. Low-temperature fluorescence studies in frozen aqueous buffer matrices
      showed that the (+)-trans adduct adopts primarily an external conformation with
      only minor interactions with the helix, but a smaller fraction (approximately
      25%) appears to exists in a partially base-stacked conformation. The (-)-trans
      adduct exists almost exclusively (approximately 97%) in an external conformation.
      Both cis adducts were found to be intercalated; strong electron-phonon coupling
      observed in their FLN spectra provided additional evidence for significant pi-pi
      stacking interactions between the pyrenyl residues and the bases. FLN
      spectroscopy is shown to be suitable for distinguishing between trans and cis
      adducts, but lesions with either (+)- or (-)-trans, or (+)- or (-)-cis
      stereochemical characteristics showed very similar vibrational patterns.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578904
TI  - Fluorescence anisotropy of tyrosine using one-and two-photon excitation.
AB  - We examined the emission spectra and steady-state anisotropy of tyrosyl
      fluorescence with two-photon excitation from 565 to 578 nm. The emission spectra
      of phenol and N-acetyl-L-tyrosinamide (NATyrA) were all the same for one-photon
      excitation (OPE) and two-photon excitation (TPE), and the tyrosine emission from
      ribonuclease A showed 10-nm shift to longer wavelengths with TPE. Surprisingly,
      the anisotropy of tyrosine, NATyrA and Leu5-enkephalin in frozen solution were
      near zero for TPE as compared to near 0.3 for OPE. Low values of the anisotropy
      near 0.05 were also found for phenol and ribonuclease A. A low anisotropy appears
      to be a basic characteristic of tyrosine or tyrosyl residues with two-photon
      excitation.

PMID- 7578907
TI  - Incorporation of cholesterol oxidation products into cell lipids and their
      influence on the proliferation of cultured cardiomyocytes.
AB  - We have investigated the incorporation of cholesterol oxidation products into
      cardiomyocyte lipids and related this to changes in cell proliferation, evaluated
      by measuring cellular protein content. Primary cultures of neonatal rat
      ventricular cells were supplemented with scalar concentrations of several
      cholesterol oxidation products (cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol, 5
      alpha-cholestane-3 beta, 5, 6 beta-triol, 5-cholesten-3 beta, 4 beta-diol, 5
      cholesten-3 beta-ol-7-one, and 5-cholesten-3-one). Although all the cholesterol
      oxidation products were incorporated into the cardiomyocyte lipids when added to
      the medium at a concentration higher than 0.5 microM, the extent of the
      incorporation of the different cholesterol oxidation products differed, depending
      on the concentration in the culture medium and on the chemical structure of the
      compound. The effects of the cholesterol oxidation products on the cellular
      protein content were also different: 5 alpha-cholestane-3 beta, 5, 6 beta-triol
      was shown to be the most potent inhibitor of cell proliferation, followed by
      cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol, 5-cholesten-3 beta, 4 beta-diol and 5
      cholesten-3 beta-ol-7-one. 5-Cholesten-3-one did not affect the cellular protein
      content. The ability of cholesterol oxidation products to inhibit cell
      proliferation, and their capacity to increase the permeability of the plasma
      membrane to calcium, could be deleterious for cardiac cells.

PMID- 7578908
TI  - Assessment of subrenal banding of the abdominal aorta as a method of inducing
      cardiac hypertrophy in the guinea pig.
AB  - The aims of this study were to develop a model of left ventricular hypertrophy in
      the guinea pig using the technique of aortic banding below the level of the renal
      arteries, and to characterize any cardiac electrophysiological changes induced.
      Female guinea-pigs were either sham operated or the abdominal aorta was partially
      occluded by banding around a 23 or 25 G needle. Following recovery, animals were
      monitored for 10 weeks. The left ventricular dry weight to body weight ratio was
      similar in sham (0.326 +/- 0.01 mg/g, n = 12) and aortic banded guinea pigs
      (0.308 +/- 0.1 mg/g, n = 11). Conscious mean arterial blood pressure was also not
      modified by the aortic banding 10 weeks after operation (72 +/- 16 (sham) vs 71
      +/- 1 mmHg). The action potential characteristics measured in isolated superfused
      left papillary muscle stimulated at 1 Hz were similar in sham and aortic banded
      groups. The action potential duration measured at 50 and 90% of repolarization
      tended to be longer in muscle from aortic banded (122.4 +/- 10 ms ADP50 and 155.2
      +/- 9.5 ms APD90) than sham operated animals (105.8 +/- 8.4 and 142.2 +/- 6.2 ms)
      but these differences were not statistically significant. Hypoxia abbreviated the
      cardiac action potential to a similar degree in muscle from sham and aortic
      banded animals. It is concluded that sub-renal aortic banding with a 23 or 25G
      needle fails to develop left ventricular hypertrophy in the guinea pig 10 weeks
      after operation.

PMID- 7578906
TI  - Cellular basis of ventricular remodeling after myocardial infarction in rats.
AB  - The remodeling of the spared non-ischemic left ventricular myocardium after
      different time intervals from the occlusion of the left coronary artery was
      examined in rats. In the presence of large infarcts, ventricular failure
      developed two to three days after surgery, because of chamber dilation and
      thinning of the wall, resulting in an average 7.5-fold increase in diastolic
      stress on the surviving myocardium. Mural thinning of the ventricular wall remote
      from and bordering the infarction occurred through side-to-side slippage of
      myocytes and capillaries within the wall. Although an average hypertrophic growth
      of 22% of the spared myocytes has been found, this amount of hypertrophy was
      insufficient to restore normal myocardial function. Long-term cardiac
      restructuring after infarction was characterized by the persistence of chamber
      dilatation and thinning of the ventricular wall. In addition to the side-to-side
      slippage, lengthening of the myocytes was an important cause of ventricular
      changes. As the reactive hypertrophy of the unaffected ventricle was insufficient
      to re-establish the ratio of ventricular mass to chamber volume, the diastolic
      stress remained elevated and decompensated eccentric ventricular hypertrophy
      developed. The anatomical remodeling of the spared left ventricular myocardium is
      an important conditioning factor in the short- and long-term outcome of ischemic
      cardiomyopathy.

PMID- 7578909
TI  - The effects of distension of the stomach and the descending colon on phasic
      coronary blood flow in the anesthetized pig.
AB  - Previous studies in anesthetized animals showed that distension of the stomach or
      the descending colon primarily caused decreases in mean coronary blood flow.
      Whether these responses occurred during systole or diastole was not investigated.
      The present work was planned to study the primary effects of the distension of
      the two viscera on phasic coronary blood flow in the anesthetized pig. In ten
      animals, the stomach and the descending colon were distended at constant volume
      by injecting warm Ringer solution into intravisceral balloons (0.8 and 0.25 l
      respectively) while preventing changes in heart rate and arterial blood pressure.
      Distensions of the stomach or the descending colon caused a decrease in mean
      coronary blood flow in each pig. However, the decrease elicited by gastric
      distension occurred only during diastole, while the decrease caused by descending
      colon distension involved both systolic and diastolic coronary blood flows. The
      same effects on phasic coronary blood flow were observed during experiments in
      which the decreases in mean coronary blood flow elicited by distension of the
      stomach or the descending colon were further augmented by adding the distension
      of the second viscerum. The results indicate that the coronary vasoconstriction
      caused by gastric distension mainly involves the vessels which supply the
      subendocardial layers of the myocardium, while that caused by descending colon
      distension also involves the vessels which supply the subepicardial layers. The
      vasoconstrictor effect on the subendocardial coronary circulation is enhanced by
      the combined distension of the two viscera.

PMID- 7578914
TI  - Exercises in (col)lateral thinking.

PMID- 7578913
TI  - A subpopulation of intracardiac neurons from the guinea pig heart expresses
      substance P binding sites.
AB  - The distribution of binding sites for substance P labeled with [125I]-Bolton
      Hunter-reagent was studied in a mixed cell culture preparation from newborn
      guinea-pig atria and interatrial septum. A relatively small subpopulation of
      intracardiac neurons expressed substance P binding sites. These neurons exhibited
      a range of densities of labeling and could be heavily, moderately or lightly
      labeled with autoradiographic grains. In most cases, the autoradiographic grains
      were restricted to the neuronal cell body and more proximal regions of the
      neurites in culture. Intracardiac neurons expressing substance P binding sites
      were seen in close association with unlabeled neurons. The density of labeling
      and the distribution of autoradiographic grains over individual intracardiac
      neurons did not appear to be related to whether they were mono- or binucleate or
      their associated cell types. The possibility that the substance P binding sites
      demonstrated here represent functional receptors on intracardiac neurons and
      their potential role in the heart is discussed.

PMID- 7578911
TI  - Effects of an early treatment with lisinopril and isosorbide-5-mononitrate on
      hemodynamics and late ventricular remodelling in rats with 9-week myocardial
      infarction.
AB  - This study was undertaken to assess whether the converting enzyme inhibitor
      lisinopril, and the long-acting nitrate, isosorbide-5-mononitrate, affect left
      ventricle dysfunction and anatomical remodelling in rats with myocardial
      infarction. Lisinopril, isosorbide-5-mononitrate or vehicle were given to rats (n
      = 10-14 per group) immediately after coronary artery occlusion (by an intravenous
      bolus) and then for nine weeks (in drinking water). At the end of the study, left
      ventricular pressures were measured, the heart arrested in diastole, and infarct
      size, left ventricular chamber volume and wall thicknesses measured. Lisinopril
      significantly lowered systemic blood pressure and left ventricular systolic
      pressure in rats with small (< 15% scarred tissue of the left ventricle) and
      large (> 15%) infarcts; the weight of the left ventricle (including the septum)
      was reduced by 24% and 28% in animals with small and large infarcts,
      respectively. Lisinopril lowered left ventricular end-diastolic pressure (by 33%
      and 39%) and chamber volume (by 4% and 34%) in rats with small and large
      infarcts, respectively, compared with controls (NS). The combined anatomical and
      hemodynamic changes led to a reduction of the circumferential wall stress by 20%
      and 44% in lisinopril-treated rats with small and large infarcts, respectively
      (NS). No significant changes were seen in the nitrate-treated hearts compared
      with controls. Lisinopril, given early after myocardial infarction and continued
      for nine weeks, significantly affected cardiac hemodynamics and ventricular
      weights in rats with infarcts of different sizes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7578910
TI  - The functional and metabolic responses of the heart to catecholamines are
      attenuated in diabetic rats.
AB  - Many studies have shown that the contractile response of the rat left ventricle
      is impaired in diabetes mellitus. Few studies have examined the acute in vivo
      effects of catecholamines on the right ventricle of diabetic rats. The present
      study investigates the acute in vivo effects of norepinephrine (100 micrograms.kg
      1.h-1 continuous intravenous infusion for 15 minutes) on the function of the
      right and left ventricle of diabetic rats. The effects of isoproterenol (25 mg.kg
      1, subcutaneously) on the activity of glucose-6-phosphate dehydrogenase, the
      first and rate limiting enzyme of the oxidative pentose phosphate pathway, and on
      adenine nucleotide biosynthesis of the diabetic heart were also examined.
      Diabetes mellitus was induced by a single intravenous injection of streptozotocin
      (60 mg.kg-1) 4 weeks before measurements. The hemodynamic measurements were made
      on intact, anesthetized rats with Millard ultraminiature pressure tip catheters.
      The basal hemodynamic measurements (left ventricular systolic pressure, diastolic
      aortic pressure, left ventricular dP/dtmax, right ventricular systolic pressure
      and right ventricular dP/dtmax) as well as glucose-6-phosphate dehydrogenase
      activity and adenine nucleotide biosynthesis were the same in the diabetic
      animals as in the controls. Heart rate was slower in the diabetics.
      Norepinephrine, after 15 minutes of intravenous infusion, induced a marked
      increase in heart rate, left ventricular dP/dtmax, right ventricular systolic
      pressure and right ventricular dP/dtmax; whereas left ventricular systolic
      pressure and diastolic aortic pressure remained unchanged. Isoproterenol caused a
      pronounced stimulation of both cardiac glucose-6-phosphate dehydrogenase activity
      (after 24 hours) and adenine nucleotide biosynthesis (after 5 hours).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578912
TI  - Left ventricular dysfunction induced by occlusion of coronary arteries in
      conscious dogs.
AB  - The aim of the present study was to investigate stable left ventricular
      dysfunction resulting from severe myocardial ischemia in conscious dogs, in order
      to evaluate the action of cardiotonic agents under pathological conditions
      mimicking moderate cardiac failure. Mongrel dogs with a catheter implanted in the
      left ventricle were trained on a treadmill and subjected to a standardized
      exercise before and after a Harris-type ligation of the anterior descending
      branch of the left coronary artery in two stages. Two weeks later the lower third
      of the left circumflex coronary branch was also occluded, and the exercise test
      repeated for at least two additional weeks to evaluate the changes in the left
      ventricular function indicated by left ventricular systolic pressure, end
      diastolic pressure, heart rate, positive and negative dP/dtmax and dP/dt/P.
      Noninvasive radionuclide investigations of the left ventricular function and
      myocardial perfusion were done before and after the development of cardiac
      failure. Following occlusion of the anterior descending and circumflex coronary
      arteries, the baseline end-diastolic pressure increased from 7.6 +/- 2.3 mmHg to
      23.3 +/- 3.0 mmHg (p < 0.05) and increased even further during exercise (to 49.2
      +/- 3.5 mmHg, p < 0.05). After the development of cardiac failure, no substantial
      change occurred in the end-diastolic pressure, either during rest or repeated
      exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578915
TI  - Ventricular remodeling in global ischemia.
AB  - To determine the effects of chronic constriction of the left coronary artery on
      the function and structure of the heart, coronary artery narrowing was surgically
      induced in rats and ventricular pump performance, extent and distribution of
      myocardial damage, and the hypertrophic and hyperplastic response of myocytes
      were examined. Alterations in cardiac hemodynamics were found in all rats, but
      the characteristics of the physiological properties of the heart allowed a
      separation of the animals into two groups which exhibited left ventricular
      dysfunction and failure, respectively. Left ventricular hypertrophy occurred in
      both groups and was characterized by ventricular dilatation and wall thinning
      which were more severe in the failing animals. Multiple foci of myocardial damage
      across the wall were seen in all animals but tissue injury was more prominent in
      the endomyocardium and in failing rats. The anatomical and hemodynamic changes
      resulted in a significant increase in diastolic wall stress which paralleled the
      depression in ventricular performance. Myocyte cell loss and myocyte cellular
      hypertrophy were more severe with ventricular failure than with dysfunction.
      Finally, diastolic overload appeared to be coupled with activation of the DNA
      synthetic machinery of myocytes and nuclear mitotic division. In conclusion, a
      fixed lesion of the left coronary artery leads to abnormalities in cardiac
      dynamics with marked increases in diastolic wall stress and extensive ventricular
      remodeling in spite of compensatory myocyte cellular hypertrophy and hyperplasia
      in the remaining viable tissue.

PMID- 7578917
TI  - Aflatoxin M1 8,9-epoxide: preparation and mutagenic activity.
AB  - Treatment of aflatoxin M1 (AFM1) with dimethyldioxirane in an anhydrous mixture
      of CH2-Cl2 and acetone afforded the corresponding aflatoxin M1 8,9-epoxide (AFM1
      E) in practically quantitative yield. This highly reactive intermediate was
      identified by 1H NMR and characterized by its neat conversion into the
      corresponding trans-methoxyhydrin derivative 1. The analysis of the 1H NMR
      spectrum of the above epoxide revealed that one stereoisomer, which should be
      that with the exo configuration, was present as major component. The
      mutagenicities of AFM1-E, the parent mycotoxin (AFM1), aflatoxin B1 (AFB1), and
      its epoxide (AFB1-E) were assessed by using a sensitive improved Ames test with
      the Salmonella typhimurium strain TA-100. AFM1 and AFB1 had specific mutagenic
      activities (SMA) of 13 and 121 revertants/ng, respectively, with S9 metabolic
      activation. AFM1-E was mutagenic with and without metabolic activation showing
      SMA of 13 and 12 revertants/ng, respectively. AFB1-E had a SMA of 42 and 29
      revertants/ng, with and without S9 metabolic enzymes, respectively. These results
      suggest that the epoxidation of AFM1 can constitute a major route accounting for
      the cytotoxic effects elicited by this mycotoxin and that AFM1-E is not as active
      as AFB1-E in reacting with the constituents of the mutagenicity assay.

PMID- 7578918
TI  - Synthesis of [4,5,6,8-(13)C4]guanine, a reagent for the production of internal
      standards of guanyl DNA adducts.
AB  - Using readily available labeled compounds, [4,5,6,8-(13)C4]guanine was
      synthesized in high overall yield. Intermediates as well as the final product
      were characterized by 1H NMR, 13C NMR, and high resolution mass spectrometry. The
      labeled guanine was used to generate [13C4]-labeled analogs of the guanine
      adducts, N2,3-ethenoguanine and 7-(2-hydroxyethyl)guanine. The application of
      such adducts in isotope dilution mass spectrometry was illustrated with DNA
      samples from rats exposed to two different mutagenic compounds, vinyl chloride
      and ethylene oxide.

PMID- 7578916
TI  - o-Methoxy-4-alkylphenols that form quinone methides of intermediate reactivity
      are the most toxic in rat liver slices.
AB  - The effects of p-alkyl substituents on the relative cytotoxicity of 4-alkyl-2
      methoxyphenols were investigated in isolated rat liver slices. The derivatives of
      4-alkyl-2-methoxyphenol studied were 4-methyl- (creosol), 4-ethyl-, 4-propyl-, 4
      isopropyl-, 4-allyl-2-methoxyphenol (eugenol), as well as 4-allyl-2,6
      dimethoxyphenol. The data were correlated with previous microsomal experiments
      which showed that all of the 4-alkyl-2-methoxyphenols were converted to quinone
      methides (QMs; 4-methylene-2,5-cyclohexadien-1-ones) via a cytochrome P450
      catalyzed process [Bolton, J. L. Comeau, E., and Vukomanovic, V. (1995) Chem.
      Biol. Interact., in press]. The present investigation showed little correlation
      between the rate of QM formation in microsomes and the relative toxicities of the
      alkylphenols, unless the QMs formed were of similar reactivity. In contrast, a
      plot of alkylphenol toxicity versus the relative hydrolysis rates of QMs derived
      from these phenols fit a parabolic equation with a minimum at the data for 4
      isopropyl-2-methoxyphenol. These data suggest that in vivo oxidation of phenols
      to QMs which have lifetimes in the 10 s-10 min range results in cytotoxicity. QMs
      with reactivities outside this window are less toxic since the electrophile is
      either too stable for reaction with cellular nucleophiles or too reactive for
      nucleophilic cellular macromolecules to compete with solvent. These data suggest
      that a reactivity window exists for QMs which is a primary determinant of the
      extent of cytotoxic injury caused by these reactive electrophiles.

PMID- 7578920
TI  - Peroxidase-catalyzed oxidation of pentachlorophenol.
AB  - Pentachlorophenol (PCP) was shown to function as a reducing substrate for
      horseradish peroxidase (HRP) and to stimulate the HRP-catalyzed reduction of 5
      phenyl-4-penten-1-yl hydroperoxide (PPHP) to 5-phenyl-4-penten-1-ol. HRP
      catalyzed the hydroperoxide-dependent oxidation of PCP, using H2O2, PPHP, or
      ethyl hydroperoxide as substrates, as evidenced by UV spectroscopic and reverse
      phase HPLC analysis of reaction mixtures. The major oxidation product was
      tetrachloro-1,4-benzoquinone which was identified on the basis of electronic
      absorption spectroscopy, mass spectrometry, and cochromatography with authentic
      standard. HRP-catalyzed oxidation of PCP yielded relatively stable, ESR
      detectable pentachlorophenoxyl radical intermediates whose ESR spectra consisted
      of a symmetrical single line without hyperfine structure. Substitution of natural
      abundance isotopically-labeled PCP with 13C-labeled PCP resulted in broadening of
      the ESR signal line width from 6.1 G to 13.5 G. ESR spin trapping studies, with
      alpha-(1-oxy-4-pyridyl)-N tert-butylnitrone (4-POBN) as the spin trap
      demonstrated identical spectra using natural abundance isotopically-labeled PCP
      versus 13C-labeled PCP, suggesting oxyl addition, rather than carbon-centered
      radical addition to 4-POBN. The computer simulation of the observed spectra is
      consistent with two distinct 4-POBN adducts, with relative abundances of
      approximately 3:1, and hyperfine coupling constants of alpha N = (14.61 G)/alpha
      H = 1.83 G and alpha N = (14.76 G)/alpha H = 5.21 G, respectively. Mechanisms for
      the hydroperoxide-dependent, HRP-catalyzed oxidation of PCP are presented that
      are consistent with these results.

PMID- 7578922
TI  - Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Involvement of
      reactive oxygen species during the interaction with oxyhemoglobin.
AB  - Ferrihemoglobin formation by 4-(dimethylamino)phenol (DMAP), a potent cyanide
      antidote, is influenced by GSH under formation of various glutathione S
      conjugates. Two of these were shown to be still reactive and able to produce
      ferrihemoglobin. The mechanism of ferrihemoglobin formation is fundamentally
      different from that found with the parent compound. First of all, induction
      periods of ferrihemoglobin formation were observed when 4-(dimethylamino)-2
      (glutathion-S-yl)-phenol (2-GS-DMAP) and 4-(dimethylamino)-2,6-bis(glutathion-S
      yl)phenol (2,6-bis-GS-DMAP) reacted with oxyhemoglobin at 100% and 20% oxygen,
      but not at 2% oxygen. This behavior points to thioether activation by
      autoxidation. Autoxidation proceeded in an autocatalytic manner, and the process
      was markedly modified by reducing agents, e.g., ferrihemoglobin and GSH, and by
      nucleophiles like GSH. Superoxide dismutase extended the lag phase of
      autoxidation and ferrihemoglobin formation. Catalase diminished markedly
      ferrihemoglobin formation, particularly at low oxygen pressure. The extent of
      this effect was much higher than expected if H2O2 had formed ferrihemoglobin
      directly. Conceivably, H2O2 might react with the thioethers or their oxidation
      products to give hitherto unidentified compounds of high catalytic activity in
      ferrihemoglobin formation. The results indicate that ferrihemoglobin formation by
      reactive glutathione conjugates of DMAP is essentially not a co-oxidation process
      as found with the parent DMAP and other aminophenols, but is mainly caused by an
      autocatalytic autoxidation process with formation of various reactive
      intermediates including superoxide radical anions and hydrogen peroxide. It
      appears that glutathione conjugation of autoxidizable aromatics does not
      necessarily lead to inactive phase II metabolites but opens new avenues of
      toxication reactions that may be a broader toxicological significance.

PMID- 7578921
TI  - DNA base and deoxyribose modification by the carbon-centered radical generated
      from 4-(hydroxymethyl)benzenediazonium salt, a carcinogen in mushroom.
AB  - Modification of the base and the sugar moieties of DNA with 4
      (hydroxymethyl)benzenediazonium salt (HMBD), a carcinogen in the mushroom
      Agaricus bisporus, was investigated. When deoxyribonucleosides dGuo, dAdo, dThd,
      and dCyd were incubated with HMBD at pH 7.4 and 37 degrees C, the levels of all
      the nucleosides were decreased. The decrease was inhibited by ethanol or Cys.
      When deoxyribose was incubated with HMBD, malonaldehyde was released as assessed
      by the thiobarbituric acid reactivity. The release was inhibited by ethanol.
      Major products of the reaction of dGuo and dAdo with HMBD were isolated, and
      their structures were established to be 8-[4-(hydroxymethyl)phenyl]dGuo (8-HMP
      dGuo) and 8-[4-(hydroxymethyl)phenyl]dAdo), respectively. Calf thymus DNA treated
      with HMBD was enzymatically digested into nucleosides, in which 8-HMP-dGuo and 8
      HMP-dAdo were detected. Formation of the modified nucleosides in DNA was
      inhibited by ethanol or 2-mercaptoethanol. Malonaldehyde was released from DNA
      treated with HMBD, which indicated that the deoxyribose moiety of DNA had been
      damaged. The results indicate that the 4-(hydroxymethyl)phenyl radical generated
      from HMBD can directly modify the base and the sugar moieties of DNA under the
      mild conditions. Inhibitory effect of ethanol was ascribable to its scavenging
      activity for the carbon-centered radical. The inhibitory effect of Cys and 2
      mercaptoethanol was found to be due to the formation of the reversible adducts
      between HMBD and the SH compounds.

PMID- 7578919
TI  - Multiple fluorescence lifetimes for oligonucleotides containing single, site
      specific modifications at guanine and adenine corresponding to trans addition of
      exocyclic amino groups to (+)-(7R,8S,9S,10R)- and (+)-(7S,8R,9R,10S) -7,8
      dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
AB  - Fluorescence decay profiles of four oligonucleotide duplexes, [table: see text]
      ((+)- and (-)-trans-1) and [table: see text] ((+)- and (-)-trans-2), in which an
      exocyclic amino group of deoxyadenosine (A*) or deoxyguanosine (G*) has been
      alkylated by trans opening at C-10 of the epoxide group of either the (+)
      (R,S,S,R)- or (-)-(S,R,R,S)-enantiomer of (+/-)-7 beta,8 alpha-dihydroxy-9
      alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE in which the
      benzylic 7-hydroxy group and the epoxide oxygen are trans), exhibit more than one
      fluorescence lifetime. Decay profiles of the oligomers, measured at 15 degrees C
      with excitation and emission wavelengths of 335 and 400 nm, respectively, have
      been analyzed using a triple-exponential decay law. Results for (+)- and (-)
      trans-1 and -2 have been compared with results for the modified, single-stranded
      oligonucleotides ((+)- and (-)-trans-SS-1, and (+)- and (-)-trans-SS-2) and for
      the cis and trans opened products formed on alkylation at the 6-amino group of 2'
      deoxyadenosine 5'-phosphate by (+)-(R,S,S,R)-BPDE ((+)-trans- and (+)-cis-A). The
      profiles of (+)-trans- and (+)-cis-A are well represented by single-exponential
      decay laws with lifetimes of 86 and 110 +/- 3 ns, respectively. For the single-
      and double-stranded oligomer adducts, which exhibit at least three fluorescence
      lifetimes, two of the lifetimes are short (0.5-14 +/- 1 ns) and one is long (35
      59 +/- 3 ns). The fluorescence lifetimes and the amplitudes of the long-lived
      components in the decay profiles of the double-stranded oligomer adducts are
      generally smaller than those for the corresponding single-stranded adducts. The
      data provide evidence that the double-stranded oligomer adducts exist as multiple
      conformations. Previously reported NMR results suggest that the short lifetime
      fluorescence components are due to major adduct conformations in which the
      pyrenyl group is intercalated ((+)- and (-)-trans-1) or lies in the minor groove
      ((+)- and (-)-trans-2). The observation of long lifetime fluorescence species for
      the double-stranded oligomers is consistent with the presence of minor
      conformations (approximately 1-5%) in which the double-stranded oligomer either
      is locally denatured or is a mixture of locally denatured double-stranded
      conformations and equilibrium concentrations of single-stranded oligomers.

PMID- 7578924
TI  - Reaction of singlet oxygen with 2'-deoxyguanosine and DNA. Isolation and
      characterization of the main oxidation products.
AB  - The reaction of singlet molecular oxygen with 2'-deoxyguanosine and DNA was
      studied. Emphasis was placed on the identification and characterization of the
      main methylene blue mediated type II (singlet oxygen) oxidation products of 2'
      deoxyguanosine and its corresponding 3',5'-di-O-acetylated derivative. Two major
      oxidation products of 2'-deoxyguanosine were isolated and characterized by mass
      spectrometry analysis and extensive 1H and 13C NMR measurements as the two 4R*
      and 4S* diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine. The
      addition of 1O2 was also found to occur to the base moiety of the corresponding
      3',5'-di-O-acetylated derivative. Methylene blue mediated photosensitization of
      2'-deoxyguanosine led also to the production of 7,8-dihydro-8-oxo-2'
      deoxyguanosine, but in a relatively lower yield with respect to the two above
      diastereomers. The participation of singlet oxygen in the mechanism of formation
      of these oxidation products was confirmed. A reasonable mechanism involving the
      transient formation of an unstable endoperoxide produced through a Diels-Alder
      1,4-cycloaddition of singlet oxygen to the purine ring is suggested. Quantitative
      analysis allowed us to demonstrate that the two diastereomers of 4,8-dihydro-4
      hydroxy-8-oxo-2'-deoxyguanosine are the main singlet oxygen oxidation products of
      the guanine moiety within nucleosides, whereas 7,8-dihydro-8-oxoguanine was found
      to be the major 1O2 oxidation product of guanine in double-stranded DNA.

PMID- 7578923
TI  - Solution conformation of the N-(deoxyguanosin-8-yl)aminofluorene adduct opposite
      deoxyinosine and deoxyguanosine in DNA by NMR and computational characterization.
AB  - Two-dimensional proton NMR and energy minimization computations have been
      employed to characterize the conformations of the N-(deoxyguanosin-8
      yl)aminofluorene adduct [(AF)G] positioned opposite deoxyguanosine in one, and
      opposite deoxyinosine in another DNA undecamer duplex in aqueous solution. The
      two oligomer duplexes used in this study are d[C1-C2-A3-T4-C5-(AF)G6-C7-T8-A9-C10
      C11].[G12-G13-T14 -A15-G16-X17-G18- A19-T20-G21-G22], where X17 was deoxyinosine
      in one duplex and deoxyguanosine in another. The exchangeable and nonexchangeable
      protons of the DNA are well resolved and narrow in the NMR spectra of the
      duplexes, and the base and sugar nucleic acid protons were assigned by NOESY and
      COSY data sets. All nine of the nonexchangeable aminofluorene ring protons were
      also assigned for the duplex that has deoxyinosine across from the modification
      site, and the (AF)G-I structure was employed to model the (AF)G-G one. The NOE
      distance restraints establish that the glycosidic torsion angle at (AF)G6 is syn.
      All other glycosidic torsion angles are anti, Watson-Crick type A.T and G-C base
      pairing is intact throughout the duplex except at the site of modification, and
      the helix maintains an overall B-DNA conformation. The syn orientation at the
      (AF)G6 places the aminofluorene ring in the B-DNA minor groove in a conformation
      similar to that found previously when the (AF)G was positioned opposite
      deoxyadenosine [Norman et al. (1989) Biochemistry 28, 7462-7476].

PMID- 7578925
TI  - Different mechanisms of aralkylation of adenosine at the 1- and N6-positions.
AB  - The eight products resulting from opening of either enantiomer of styrene oxide
      at the alpha- or beta-carbon by the 1- or N6-positions of adenosine were prepared
      and their configurations assigned. These markers allowed the mechanism of
      aralkylation of adenosine by styrene oxide to be investigated. It was found that
      formation of alpha-substituted products at the 1-position of adenosine involved
      total inversion of stereochemistry, whereas at the N6-position inversion:
      retention was approximately 6:1. These differences in stereochemistry suggest
      that a more ionic form of styrene oxide is involved in N6-aralkylation than in 1
      aralkylation of adenosine. In the course of these studies, it was found that 1
      substituted adenosines at the alpha- and beta-carbon of styrene oxide undergo
      Dimroth rearrangement at neutral pH and 37 degrees C and that the former compound
      also deaminates fairly readily under these conditions.

PMID- 7578926
TI  - Laser pulse-induced photochemical strand cleavage of site-specifically and
      covalently modified (+)-anti-benzo[a]pyrene diol epoxide-oligonucleotide adducts.
AB  - The specificity of the laser pulse-induced photocleavage method [Boles, T. C.,
      and Hogan, M. E. (1986) Biochemistry 25, 3039] for detecting the sites of
      covalent binding of benzo[a]pyrene diol epoxide in DNA was investigated using
      site-specifically modified oligonucleotide duplexes
      d(CTCACAT[G*]TACACTCT).d(GAGAGTGTACATGTGA), where [G*] is the adducted guanine
      residue (+)-trans-anti-BPDE-N2-dG (anti-BPDE = 7 beta,8 alpha- dihydroxy-9
      alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). The appropriate
      oligonucleotide strands were 32P-end-labeled, and the duplexes were irradiated
      with a pulse train of 355 nm Nd:YAG laser pulses (approximately 300 mW/cm2). The
      products of the photocleavage reaction were analyzed by denaturing gel
      electrophoresis. The major observed products included the intact oligonucleotide
      strand that had lost the BPDE residue, and shorter oligonucleotide fragments
      arising from strand scission at the BPDE-modified guanine residue and at nearby
      flanking bases. Photocleavage at the BPDE-modified G is dominant (approximately
      50 +/- 5% of the sum of all of the shorter oligonucleotide fragments), and
      cleavage extends to at least 4 bases on the 5'-side, and 7 bases on the 3'-side
      of the BPDE-modified G residue; the probability of cleavage diminishes with
      increasing distance from the modified G residue. On the unmodified complementary
      strand, nonspecific strand cleavage is also observed, but the probability of
      cleavage is > or = 20 times smaller than at the BPDE-modified G residue on the
      modified strand. The photocleavage method thus preferentially causes strand
      scission at the sites of BPDE modification, but the occurrence of strand cleavage
      with lower probabilities at neighboring sites is also significant.

PMID- 7578928
TI  - Alkylation of oxytocin by S-(2-chloroethyl)glutathione and characterization of
      adducts by tandem mass spectrometry and Edman degradation.
AB  - S-(2-Chloroethyl)glutathione (CEG), an alkylating agent formed by glutathione
      conjugation with 1,2-dichloroethane (DCE), is able to alkylate DNA and proteins.
      As a prelude to identification of specific protein alkylation sites, the peptide
      oxytocin was alkylated by CEG, and tandem mass spectrometry was used to identify
      the alkylation sites. It was found that mono-, bis-, and tris-adducts can result
      from alkylation of reduced oxytocin and that tandem mass spectrometry
      differentiated (S-[2-(Cys1)ethyl]glutathione)oxytocin (mono-adduct Cys-1) from (S
      [2-(Cys1,6)ethyl]glutathione)oxytocin (mono-adduct Cys-6). Manual Edman
      degradation was used to eliminate the possibility that alkylation has occurred at
      Tyr-2 rather than at Cys-1 in the case of (S-[2
      (Cys1,6)ethyl]glutathione)oxytocin (bis-adduct) and mono-adduct Cys-1. A mono
      adduct homodimer resulting from alkylation at Cys-6 and disulfide bridge
      formation through Cys-1 was also identified. Oxidized oxytocin formed two minor
      adducts, representing less than 5% of the oxytocin present in the reaction
      mixture. These findings demonstrate that alkylation of oxytocin by the
      episulfonium ion of CEG did occur, as evidenced by tandem mass spectrometry, and
      that characterization of these adducts will aid in the identification of
      alkylated amino acids in proteins exposed to CEG.

PMID- 7578927
TI  - A comparative study of mouse liver proteins arylated by reactive metabolites of
      acetaminophen and its nonhepatotoxic regioisomer, 3'-hydroxyacetanilide.
AB  - Acetaminophen (4'-hydroxyacetanilide), a widely used analgesic/antipyretic drug,
      is hepatotoxic in large doses, whereas the m-hydroxy isomer of acetaminophen, 3'
      hydroxyacetanilide, is not hepatotoxic. Both are oxidized by mouse liver
      cytochromes P-450 to reactive metabolites that bind covalently to hepatic
      proteins. Because previous studies have shown that peak levels of liver protein
      adducts formed after the administration of each of these compounds to mice are
      nearly equivalent, and because liver protein adduct formation correlates with
      hepatotoxicity caused by acetaminophen in mice, we investigated the abundance and
      patterns of protein adducts formed by acetaminophen and its regioisomer for
      significant differences. Hepatotoxic doses of acetaminophen to mice significantly
      altered the abundances of several liver proteins 2 h after dosing as revealed by
      densitometric analysis of two-dimensional electrophoretic patterns of these
      proteins. The same analysis after the administration to mice of 3'
      hydroxyacetanilide indicated that this nonhepatotoxic regioisomer of
      acetaminophen caused several similar changes in protein patterns, but also
      revealed some significant differences. Binding of radiolabeled acetaminophen and
      3'-hydroxyacetanilide to hepatic proteins corroborated and extended these
      results. Two hours after the administration of 14C-labeled analogs of these two
      compounds to mice, at a time when their extent of total covalent binding to
      hepatic proteins is approximately equivalent, there are many similarities but
      also some differences in selectivity of proteins that are adducted, as revealed
      by both one-dimensional and two-dimensional gel electrophoresis followed by
      phosphorimage analysis of radiolabel bound to protein bands. Moreover, protein
      adducts formed from 3'-hydroxyacetanilide were found to be less stable than those
      formed from acetaminophen under the conditions of electrophoretic analysis.
      Furthermore, a comparison of radiodetection and immunodetection of protein
      adducts formed from acetaminophen with an antibody specific for acetaminophen
      protein adducts indicates that the antibody detects most of the same proteins
      that are radiolabeled and that the relative quantitative contribution of various
      adducts to the overall covalent binding of acetaminophen to proteins is
      approximately the same by both methods. Thus, 3'-hydroxyacetanilide should prove
      to be a useful tool to aid in the discrimination of hepatic acetaminophen protein
      adducts that may be critical or noncritical to survival of hepatocytes.

PMID- 7578929
TI  - The efficiency of translesion synthesis past single styrene oxide DNA adducts in
      vitro is polymerase-specific.
AB  - In order to examine the effect of adenine N6 adducts of styrene oxide (SO) on DNA
      replication, 33-mer templates were constructed bearing site-specific and
      stereospecific SO modifications. Both R- and S-SO adducts were introduced at four
      different base positions within a sequence containing codons 60-62 from the human
      N-ras gene. The resulting eight templates were replicated in primer extension
      assays using the Klenow fragment, Sequenase 2.0, T4 polymerase holoenzyme,
      polymerase alpha, and polymerase beta. Replication of the damaged templates was
      analyzed under conditions defining single and/or multiple encounters between the
      polymerase and the substrate. Polymerization by all five enzymes was sensitive to
      both the local sequence context and the chirality of the SO adduct. For example,
      R-SO lesions placed at the third position of N-ras codon 61 were readily
      bypassed, whereas stereochemically-identical lesions in other sequence contexts
      were often poor substrates for replication. Similarly, R- and S-SO adducts
      introduced within identical sequences were often bypassed nonequivalently.
      Significantly, the degree of adduct-directed termination and translesion
      synthesis during replication was also dependent on the choice of polymerase.
      Although SO adducts directed termination either opposite the lesion or 1 base 3'
      to the damage using all five polymerases, templates that were poor substrates for
      bypass synthesis with one enzyme were often read-through much more efficiently
      when a different polymerase was used. Thus, the activities of these enzymes on
      the SO-modified substrates produced replication profiles, or "fingerprints", that
      were unique to each polymerase.

PMID- 7578930
TI  - Enzyme induction by L-buthionine (S,R)-sulfoximine in cultured mouse hepatoma
      cells.
AB  - Induction of Phase II enzymes of the [Ah] gene battery by L-buthionine (S,R)
      sulfoximine (BSO) and other agents was examined in mouse hepatoma Hepa-1c1c7
      cells. BSO, a nonelectrophilic inhibitor of gamma-glutamylcysteine synthetase
      (GCS), is routinely used to examine the toxicological implications of GSH
      depletion. Exposure to BSO for 24 h produced a 75-85% depletion of GSH levels,
      proportional to the inhibition of GCS activity, as well as small increases in the
      UDP-glucuronosyltransferase (UGT, 60%) and glutathione transferase (GST, 30%)
      enzyme activities in Hepa-1 wild-type (wt) cells. However, for the
      NAD(P)H:menadione oxidoreductase (NMO1) and cytosolic aldehyde dehydrogenase
      class 3 (AHD4) enzyme activities, BSO produced larger increases (110% and 170%,
      respectively). The mechanisms of NMO1 and AHD4 induction were examined further.
      In Hepa-1 wt cells, NMO1 and AHD4 activities were increased by the aromatic
      hydrocarbon inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and by the
      electrophile tert-butylhydroquinone (tBHQ), known inducing agents for these
      enzymes. However, NMO1 and AHD4 were induced in Ah receptor nuclear translocation
      defective mutant (c4) cells by BSO and tBHQ, but not by TCDD, suggesting that the
      induction by BSO and tBHQ is not Ah receptor-mediated. In wt cells, N
      acetylcysteine produced a concentration-dependent increase in intracellular
      cysteine levels, but not GSH levels, in the absence or presence of BSO.
      Furthermore, N-acetylcysteine had no effect on NMO1 activity under any conditions
      examined, suggesting that GSH levels per se, rather than change in overall thiol
      status, might be mediating increased NMO1 activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7578931
TI  - Metabolite predictions for para-substituted anisoles based on ab initio complete
      active space self-consistent field calculations.
AB  - The cytochrome P450 mediated oxidative metabolism of a series of para-substituted
      anisoles has been examined using ab initio CASSCF (complete active space self
      consistent field) calculations. On the basis of these calculations, oxidative
      metabolites were rationalized using the concept of hydrogen atom abstraction,
      spin delocalization, and hydroxyl radical recombination, which is believed to
      govern part of the oxidation and oxygenation reactions catalyzed by cytochrome
      P450. Spin distributions and energy differences between substrates, metabolic
      intermediates, and products were calculated. A comparison of the predictions with
      recent experimental findings from other laboratories supports the applicability
      of the currently used computational model for predicting qualitatively the
      oxidative metabolism by cytochrome P450.

PMID- 7578932
TI  - Direct synthesis and characterization of site-specific adenosyl adducts derived
      from the binding of a 3,4-dihydroxy-1,2-epoxybenzo[c]phenanthrene stereoisomer to
      an 11-mer oligodeoxyribonucleotide.
AB  - Site-specifically modified oligonucleotides were obtained in milligram quantities
      by reacting racemic 3t,4r-dihydroxy-1,2t-epoxy-1,2,3,4
      tetrahydrobenzo[c]phenanthrene (B[c]PhDE-2, or anti-B[c]PhDE) with the single
      deoxyadenosine (dA) residue in the oligodeoxynucleotide d(CTCTCACTTCC). Enzyme
      digestion of the covalently modified oligonucleotides with the exonuclease spleen
      phosphodiesterase yielded covalently linked B[ca]PhDE-N6-deoxyadenosyl
      monophosphate (dAMP) adducts. Comparisons of the reverse phase HPLC retention
      times and CD spectra of these B[c]PhDE-3'-dAMP mononucleotide adducts, with those
      of standards derived from the reaction of the enantiomers (+)- and (-)-anti
      B[c]PhDE with 3'-dAMP, show that two major oligonucleotide adducts (I and II)
      were obtained upon reacting racemic anti-B[c]PhDE with d(CTCTCACTTCC). In
      oligonucleotide adduct I, the lesion is a (+)-trans-anti-B[c]PhDE-N6-dA residue,
      and in oligonucleotide adduct II it is a (-)-trans-anti-B[c]PhDE-N6-dA residue.
      These assignments were further confirmed using a standard 32P postlabeling assay
      of B[c]PhDE-3'-dAMP mononucleotide adducts obtained from the digestion of
      oligonucleotides I and II by spleen phosphodiesterase. The melting points (Tm) of
      duplexes of modified oligonucleotides I and II and their natural complementary
      strands are not affected significantly by the presence of the covalently bound
      benzo[c]phenanthrenyl residues. Opposite stereoselective resistance to enzyme
      digestion by the exonucleases snake venom phosphodiesterase and spleen
      phosphodiesterase is exhibited by the stereoisomeric (+)-trans- and (-)-trans
      anti-B[c]PhDE-modified oligonucleotide adducts I and II; these results are
      consistent with the intercalative insertion of the benzo[c]phenanthrenyl residues
      on the 5'-side of the modified dA residue in adduct I, and its insertion on the
      3'-side of the dA residue in adduct II, as observed in the duplexes by high
      resolution NMR techniques [Cosman et al. (1993) Biochemistry 32, 12488-12497, and
      Cosman et all, Biochemistry, in press.

PMID- 7578933
TI  - Diaziquone-glutathione conjugates: characterization and mechanisms of formation.
AB  - The antitumor agent diaziquone (AZQ) reacts with reduced glutathione (GSH) in
      aqueous solutions and under aerobic conditions to give rise to the glutathionyl
      and hydroxyl free radicals, as well as the AZQ semiquinone. Under anaerobic
      conditions, the only radical observed was the glutathionyl radical. These
      radicals are quickly abrogated when superoxide dismutase and catalase are
      coincubated. Separately, superoxide dismutase favors the formation of thiyl
      radicals while catalase favors the formation of hydroxyl radicals and AZQ
      semiquinone. The metal chelator diethylenetriaminepentaacetic acid favors the
      production of hydroxyl radicals and AZQ semiquinone. The reaction of AZQ with GSH
      at pH 7.2 and 5.5 results in a variety of conjugates. These conjugates include
      addition of glutathione to both aziridines, displacement of the aziridines by
      GSH, and a combination of both. The majority of the conjugates are formed by
      nucleophilic attack of GSH to the AZQ aziridines or by 1,4-Michael addition to
      the AZQ quinone or a combination of both. There may be a small free radical
      component in conjugate formation, but the majority of the free radicals observed
      are from redox reactions that involve the oxidation of glutathione and the
      reduction and autoxidation of AZQ to produce oxygen radicals and hydrogen
      peroxide, a process that is enhanced by trace metal ions.

PMID- 7578935
TI  - Nitric oxide induces oxidative damage in addition to deamination in macrophage
      DNA.
AB  - Inflammatory cells such as phagocytes, neutrophils, and macrophages have been
      implicated in the pathogenesis of several forms of clinical and experimental
      tumor development. It is hypothesized that this process is mediated by the
      production of reactive species including NO., O2.-, H2O2, and ONOO- which inflict
      DNA damage. In this study, the role of NO. in combination with oxygen radicals in
      DNA damage was investigated. DNA deamination (xanthine) and oxidation [5
      (hydroxymethyl)uracil (5HMU), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPY
      G), and 8-oxoguanine (8oxoG)] products were identified in the DNA of macrophages
      (RAW264.7) activated with Escherichia coli lipopolysaccharide (LPS) and mouse
      gamma-interferon (INF-gamma). The formation of these products was inhibited by N
      methyl-L-arginine (NMA), a nitric oxide synthase inhibitor. NMA inhibited only
      the production of nitric oxide and had no effect on superoxide production. These
      results demonstrate that NO. plays a dual role in damaging the DNA of activated
      macrophages. Autoxidation of NO. leads to nitrosating species which cause
      deamination of bases. Reaction of NO. with O2.- leads to DNA oxidative damage due
      to the formation of peroxynitrite which may have HO.-like oxidizing potential.
      Another possible mechanism of oxidative damage by NO. could be the mobilization
      of free iron by NO. which could ultimately cause Fenton-type reactions.
      Therefore, nitric oxide not only leads to deamination of DNA bases but is also an
      obligatory factor in oxidative damage to DNA.

PMID- 7578936
TI  - Proceedings of the 4th Naples Workshop on Bioactive Peptides. Capri, Italy, May
      22-25, 1994.

PMID- 7578934
TI  - Enhancement of bacterial mutagenicity of bifunctional alkylating agents by
      expression of mammalian glutathione S-transferase.
AB  - Recently, we inserted the plasmid vector pKK233-2 containing rat GSH S
      transferase (GST) 5-5 cDNA into Salmonella typhimurium TA1535 and found that
      these bacteria [GST 5-5(+)] expressed the protein and produced mutations when
      ethylene or methylene dihalides were added [Thier, R., Taylor, J. B., Pemble, S.
      E., Ketterer, B., Persmark, M., Humphreys, W. G., and Guengerich, F. P. (1993)
      Proc. Natl. Acad. Sci. U.S.A. 90, 8576-8580]. After exposure to the known GST 5-5
      substrate 1,2-epoxy-3-(4'-nitrophenoxy)propane, the GST 5-5(+) strain showed
      fewer mutants than the bacteria transfected with the cDNA clone in a reverse
      orientation [GST 5-5(-)], suggesting a protective role of GST 5-5. However,
      mutations were considerably enhanced in the GST 5-5(+) strain [as compared to GST
      5-5(-)] when 1,2,3,4-diepoxybutane (butadiene diepoxide) or 1,2-epoxy-4
      bromobutane was added. The GST 5-5(+) and GST 5-5(-) bacterial stains showed
      similar responses to 1,2-epoxypropane, 3,4-epoxy-1-butene, and 1,4-dibromobutane.
      The results suggest that some bifunctional activated butanes are transformed to
      mutagenic products through GSH conjugation. We also found that the GST 5-5(+)
      strain showed enhanced mutagenicity with 1,4-dibromo-2,3-epoxybutane, 1,2-epoxy-3
      bromopropane (epibromohydrin), and (+/-)-1,4-dibromo-2,3
      dihydroxybutane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578937
TI  - Conformational studies of heterochiral peptides with diastereoisomeric residues:
      crystal and molecular structures of linear dipeptides derived from leucine,
      isoleucine, and allo-isoleucine.
AB  - The x-ray diffraction analyses of three N- and C-terminally blocked L,D
      dipeptides, namely t-Boc-D-Leu-L-Leu-OMe (1), t-Boc-L-Ile-D-aIle-OMe (2), and t
      Boc-D-aIle-L-Ile-OMe (3) containing enantiomeric or diastereomeric amino acid
      residues have been carried out. The structures were determined by direct methods
      and refined anisotropically to final Rf actors of 0.077, 0.058, and 0.072 for
      (1), (2), and (3), respectively. Peptides 1-3 all assume a similar U-shaped
      structure with phi and psi torsion angles corresponding to one of the possible
      calculated minimum energy regions (regions E and G for L residues, and F*, D* and
      H* for D residues). The peptide backbones of 1-3 are almost superimposable
      [provided that the appropriate inversion of the chiral centers of (2) is made].
      Side-chain conformations of Leu residues in peptide (1) are g- (tg-) for the L
      Leu residue and the mirrored g+ (tg+) for the D-Leu residue; however, in peptides
      (2) and (3) the conformations of the isoconfigurational side chains of the Ile or
      allo-Ile residues are (g-t) t and (tg+) t for the L-Ile and the D-allo-Ile
      moieties, respectively. In all cases, these conformations correspond to the more
      populated conformers of beta-branched residues statistically found in crystal
      structures of small peptides. The results seem to indicate that, at least in
      short peptides with enantiomeric or diastereoisomeric residues, the change in
      chirality in the main-chain atoms perturbs the backbone conformation to a lesser
      extent and the side chain conformation to a greater extent.

PMID- 7578940
TI  - Bioactive peptides: conformational studies of [Tyr4] cyclolinopeptide A.
AB  - The solid state conformational analysis of [Tyr4] cyclolinopeptide A has been
      carried out by x-ray diffraction studies. The crystal structure of the monoclinic
      form, grown from a dioxane-water mixture [alpha = 9.849 (5) A, b = 20.752 (4) A,
      c = 16.728 (5) A, beta = 98.83 (3) degrees, space group P21, Z = 2], shows the
      presence of five intramolecular N-H...O = C hydrogen bonds, with formation of one
      C17 ring structure, one alpha-turn (C13), one inverse gamma-turn (C7), and two
      beta-turns (C10, one of type III and one of type I). The Pro1-Pro2 peptide unit
      is cis (omega = 5 degrees), all others are trans. The structure is almost
      superimposable with that of cyclolinopeptide A. The rms deviation for the atoms
      of the backbones is on the average 0.33 A.

PMID- 7578938
TI  - Synthesis and biological activity of tripeptide FR113680 analogues containing
      unconventional amino acids.
AB  - In order to further develop structure-activity relationships and to get
      information about the biological active conformations we synthetized analogues
      tripeptide to the FR 113680 [Ac-Thr-D-Trp(CHO)-PheNMeBzl; Ac: acethyl], in which
      the phenylalanine residue was replaced by unconventional amino acids [1,2,3,4
      tetrahydroisoquinoline-3-carboxylic acid (Tic); (3aS, 7aS)-octahydroindole-2
      carboxylic acid (Oic); (S,S,S)-2-azabiciclo[3.3.0]octane-3-carboxylic acid (Aoc);
      3-(1'-naphthyl)alanine (Nap); phenylglicine (Phg); thienylalanine (Thi)]. The
      biological activity of the peptides was performed on guinea pig ileum for
      neurokinin 1 (NK-1) and on rat colon for neurokinin 2 (NK-2). In particular, the
      replacement of the Phe3 by the Oic (8a) gave an higher antagonist activity in
      both NK-1 and NK-2 receptors, but no improvement in selectivity with respect to
      reference tripeptide (FR113680). The compound (8a) represent the first example of
      highly potent peptides that do not contain an aromatic amino acid of the third
      position as had been previously considered essential.

PMID- 7578941
TI  - Conformation of cyclobradykinin by NMR and distance geometry calculations.
AB  - The conformation of the head-to-tail cyclic analogue of bradykinin in DMSO was
      investigated by nmr. Three sets of resonances were detected and fully assigned.
      These were attributed to the presence of three stable conformers, two of which
      were exchanging on the nmr time scale. A fourth, incomplete set of resonances was
      detected but not assigned. The three major conformers differ in the conformation
      at the three X-Pro bonds present. From nuclear Overhauser effect spectroscopy
      (NOESY) spectra, three sets of interproton distances were derived and used in NOE
      restrained distance geometry calculations. The resulting structures were refined
      by energy minimization to yield families of structures. Conformer I is
      characterized by the presence of two type VIb beta-turns between Arg1 and Gly4
      and between Phe5 and Phe8. The first beta-turn is present also in conformer II,
      while an inverse gamma-turn bridging Pro3 is the most pronounced structural
      feature of conformer III.

PMID- 7578939
TI  - Conformationally readdressed CCK-B/delta-opioid peptide ligands.
AB  - The sequence of a cholecystokinin (CCK) related peptide was modified to obtain
      analogues, which interact selectively either with CCK-B, or with delta-opioid
      receptors. Two kinds of peptides were designed, namely, the cyclic peptides of
      the H-Tyr-cyclo (D-Pen-Gly-Trp-L/D-3-transmercaptoproline)-Asp-Phe-NH2 sequence
      (compounds 1a and 1b, respectively), and the linear peptides of the H-Tyr-D-Val
      Gly-Trp-L/D-3-trans-methylmercaptoproline-Asp-Phe- NH2 sequence (compounds 2a and
      2b, respectively). The only difference between the chemical structures of the
      linear analogues compared to the cyclic ones is that one covalent bond has been
      eliminated and a sulfur atom is replaced by a methyl group. Molecular modeling
      showed that, among low-energy conformers of cyclic compounds 1, there are three
      dimensional structures compatible to the model for delta-receptor-bound
      conformer, suggested earlier [G. V. Nikiforovich, V.J. Hruby, O. Prakash, and
      C.A. Gehrig (1991) Biopolymers, vol. 31, pp. 941-955]. Results of binding assays
      fully supported the rationale for the design of compounds 1 and 2. The cyclic
      analogue 1a has Ki values of 4.5 and > 5000 nM at delta- and mu-opioid receptors,
      respectively; and IC50 values of 1.6 and > 10,000 nM for CCK-A and CCK-B
      receptors, respectively. The results of this study demonstrate a possibility to
      redirect a peptide sequence that interacts with one type of receptors (CCK-B
      receptors) toward interaction with another type (delta-opioid receptors)
      belonging to a different physiological system. This redirection could be
      performed by changing the conformational properties of the peptide with very
      minimal changes in its chemical structure.

PMID- 7578942
TI  - Conformation and interactions of bombolitin I analogues with SDS micelles and
      phospholipid vesicles: CD, fluorescence, two-dimensional NMR and computer
      simulations.
AB  - Bombolitins are five structurally related heptadecapeptides acting at the
      membrane level able to lyse erythrocytes and liposomes and to enhance the
      activity of phospholipase A2 (PLA2). In the presence of SDS or phospholipid
      vesicles bombolitins are able to form amphiphilic alpha-helical structures and
      this property seems to be the major determinant of bioactivity. In order to test
      the model of interaction between bombolitin I and membranes, an analogue was
      synthesized in which all the lysines were replaced by arginines: Ile-Arg-Ile-Thr
      Thr-Met-Leu-Ala-Arg-Ile-Gly-Arg-Val-Leu-Ala-His-Val-NH2 ([Arg2,9,12,
      Ile10]bombolitin I). The design of this sequence allowed the synthesis of a
      second analogue through a specific postsynthetic dansylation at the epsilon-amino
      group of a lysine residue replacing the original leucine residue at position 7.
      The first analogue was fully characterized by CD and two-dimensional nmr in the
      presence of SDS or phospholipid vesicles. The peptide folds into an amphiphilic
      alpha-helical conformation with the helical segment spanning the central part of
      the sequence from Ile3 to His16. This behavior is identical to that observed for
      the native sequence. The replacement of lysine residues by arginine has no
      detectable effect on the conformational preference of the peptide chain. By CD
      and fluorescence spectroscopy measurements, the fluorophore-containing analogue
      [Arg2,9,12, Lys7 (epsilon-dansyl)] bombolitin I also folded into the alpha
      helical conformation in the presence of SDS micelles or phospholipid vesicles. In
      particular, the dansyl fluorophore, which is located approximately in the middle
      of the apolar surface of the amphiphilic helix, is clearly buried in a
      hydrophobic environment when the peptide is bound to phospholipid vesicles. These
      findings support the hypothesis that the peptide helices are oriented parallel to
      the vesicle surface.

PMID- 7578944
TI  - Intramolecular electronic energy transfer in peptides carrying naphthalene and
      protoporphyrin molecules: a spectroscopic and conformational statistics
      investigation.
AB  - Short linear peptides, carrying an AA spacer in the backbone chain (AA = Aib or
      Ala), and naphthalene (N) and protoporphyrin IX (P) covalently bound to epsilon
      amino groups of lysine side chains, were synthesized. The general formula is Boc
      Leu-Leu-Lys(P)-(AA)n-Leu-Leu-Lys(N)-OtBu, with n = 0-2. The photophysical
      behavior of these compounds was investigated in water/methanol 75/25 (v/v)
      solution by steady-state and time-resolved fluorescence experiments. Quenching of
      excited naphthyl chromophore takes place by electronic energy transfer to the
      porphyrin ground state, and proceeds on a time scale of 3-8 ns, while a minor and
      slower (approximately 45 ns) fluorescence lifetime measures the decay of the
      exciplexes. The results were compared with those earlier obtained with the
      P(Ala)nN peptides (n = 0-4) in methanol solution, showing that addition of water
      does not significantly alter the dynamic relaxation behavior of the systems
      investigated, but affects the dissipation mechanism of the energy transferred to
      P. Quenching efficiencies from both fluorescence intensity and fluorescence
      lifetime measurements follow a different trend as the number of AA units
      increases, depending on whether AA = Aib or Ala, indicating that there are
      differences in the structural features of the two series of peptides.
      Consistently, CD spectral results suggest that the former compounds attain
      ordered conformations, possibly of the 3(10)-helical type, while the latter
      populate alpha-helical structures to an extent depending on the chain length. The
      ir data in dilute CD3OD or CDCl3 solution confirm this conclusion in that there
      is an increased percentage of intramolecular H bonds in the P(Aib)nN as compared
      to the corresponding P(Ala)nN peptides. The photophysical results can be well
      described by a long-range dipole-dipole interaction model, provided the
      separation distances distribution and mutual orientation of N and P groups are
      taken into account. The need of using the angular relationships between the
      probes implies that interconversion among conformational substates of
      chromophores linkages is slow on the time scale of the transfer process, very
      likely because of both the amide bond in the linkages and the bulkiness of the
      donor-acceptor pair.

PMID- 7578947
TI  - Molecular dynamics in sodium poly (L-glutamate) aqueous solutions analyzed by
      means of the stretched exponential decay of the Williams-Watts function.
AB  - The high-frequency dielectric dispersions of the sodium salt of poly(L-glutamic
      acid) aqueous solutions in the frequency range from 1 to 1,000 MHz have been
      analyzed by means of the Cole-Davidson relaxation function in the frequency
      domain and by means of the Williams-Watts relaxation function in the time domain.
      The analogies between the two descriptions are discussed on the basis of the
      analysis carried out by Lindsey and Patterson and the connections between the
      dipole-dipole correlation function based on the kinetic model for polyion
      dynamics proposed by Skinner and the Williams-Watts nonexponential decay function
      are briefly discussed.

PMID- 7578946
TI  - Conformational analysis of dolastatin 10: an NMR and theoretical approach.
AB  - A solution conformational analysis of dolastatin 10, a powerful antineoplastic
      agent, has been carried out by means of nmr techniques and theoretical
      calculations. 1H mono- and bidimensional nmr experiments, as well as 1H-13C
      heterocorrelated spectra, have been performed on CD2Cl2 solutions. The most
      interesting nmr data is a huge shielding of the aCH(25) proton of the Dov
      residue, suggesting the presence of an interaction between the N-terminal and the
      aromatic C-terminal ends of the molecule. The possibility of a head-to-tail
      intermolecular association having been discarded, the presence of a series of
      preferred folded conformation has been hypothesized. Conformational theoretical
      analysis supports the nmr hypothesis of a folded peptide-like molecule, and a
      series of possible conformers in good agreement with the experimental data have
      been analyzed.

PMID- 7578943
TI  - Conformation of parathyroid hormone antagonists by CD, NMR, and molecular
      dynamics simulations.
AB  - The conformation of two highly potent parathyroid hormone (PTH) antagonists was
      investigated in water/2,2,2-trifluoroethanol mixtures. The two peptides are
      derived from the sequence (7-34) of PTH and of PTH-related protein (PTHrP) and
      have a D-Trp replacing Gly in position 12. In the analogue derived from PTHrP,
      Lys11 was replaced by Leu to remove the residual agonist activity. The study was
      conducted by CD and two-dimensional proton magnetic resonance spectroscopy, and
      the nuclear Overhauser effects found were utilized in restrained distance
      geometry and molecular dynamics simulations. Both peptides adopt a helical C
      terminal conformation, which seems more stable in the case of the PTHrP analogue.
      A type II' beta-turn centered around D-Trp12 and Lys13 is present in both
      structures.

PMID- 7578948
TI  - Influence of proline-14 substitution on the secondary structure in a synthetic
      analogue of alamethicin.
AB  - Due to the bend introduced by proline 14 in the conformation of alamethicin
      (AcUPUAUAQUVUGLUPV UUEQFol), the role of this residue was assumed essential in
      the barrel-stave model for voltage-gated ion channels. Taking advantage of a
      previous synthetic alamethicin analogue (L2), in which all eight alpha
      aminoisobutyric (U) were replaced by leucines (AcLPLALAQLV LGLLPV LLEQFol),
      another analogue (L5) was synthesized in order to test the effects of proline-14
      substitution by an alanine (AcLPLALAQLVLGLLPVLLEQFol). Previous conductance
      experiments showed that both high voltage dependence and multistate behavior were
      conserved. In order to complement these functional results, a conformational
      study of L5 has been undertaken and compared to L2 using CD, high field nmr, and
      molecular dynamics. Results show that L5 presents a better ordered structure than
      L2 particularly in the region of the substitution and in the C-terminal part.
      These results are discussed as regards the previous hypothesis of the
      nonessential character of helix bending for the gating of voltage-dependent ion
      channels.

PMID- 7578945
TI  - Synthesis and biological evaluation of novel NK-1 tachykinin receptor
      antagonists: the use of cycloalkyl amino acids as a template.
AB  - In the course of a program aimed at synthesizing novel, potent NK-1 tachykinin
      receptor antagonists, we developed upon a bioactive model by comparing the low
      energy structures of a series of peptide and nonpeptide Substance P antagonists.
      The comparison was based on the superimposition of the aromatic rings, assuming
      that the rest of the molecule behaves predominantly as a template to arrange the
      key aromatic groups in the right spatial position. A series of 2-aminocyclohexane
      carboxylic acid analogues were then selected as the best templates for
      reproducing the postulated bioactive structure, leading to several pseudo
      peptides with interesting biological activity. According to the molecular
      modeling, these compounds exhibit a neat parallel facing of the indolyl and
      naphthyl groups at about 3 A distance. Ultraviolet absorption and steady state
      fluorescence measurements support this conclusion, showing a linear correlation
      between the spectral properties and the binding affinity of these analogues.
      Stacking of the indole ring with naphthalene gives rise to a complex
      characterized by a well-defined molar extinction coefficient. Consistently,
      steady state and lifetime fluorescence measurements suggest that the quenching
      process is ascribable to ground-state interactions between the chromophores.
      Implications of the pi stacking propensity of aromatic groups in the biological
      activity of the compounds examined are briefly discussed.

PMID- 7578949
TI  - Structural properties and thermal stability of human liver and heart fatty acid
      binding proteins: a Fourier transform IR spectroscopy study.
AB  - The secondary structure and the thermal stability of human liver (L-FABP) and
      heart (H-FABP) fatty acid-binding proteins were analyzed, in the absence and in
      the presence of oleic acid, by Fourier transform ir spectroscopy. The study was
      done in order to gain information on the secondary as well three-dimensional
      structure of L-FABP and to check the possible H-FABP self-association that has
      been found to occur in rat and pig H-FABP. Comparison of human L-FABP and H-FABP
      ir spectra reveals that, in spite of the low sequence homology, the two proteins
      have similar secondary and probably tertiary structures. The ir data indicates
      that a larger amount of beta-strands are exposed to the solvent in H-FABP as
      compared to L-FABP, suggesting minor differences in the three-dimensional
      structures of these proteins. The binding of oleic acid to L-FABP and H-FABP
      stabilizes their structures and does not modify their secondary structure. The ir
      spectra neither confirm nor exclude self-association of human H-FABP.

PMID- 7578950
TI  - Exploration of compact protein conformations using the guided replication Monte
      Carlo method.
AB  - We have studied the use of a new Monte Carlo (MC) chain generation algorithm,
      introduced by T. Garel and H. Orland [(1990) Journal of Physics A, Vol. 23, pp.
      L621-L626], for examining the thermodynamics of protein folding transitions and
      for generating candidate C(alpha) backbone structures as starting points for a de
      novo protein structure paradigm. This algorithm, termed the guided replication
      Monte Carlo method, allows a rational approach to the introduction of known
      "native" folded characteristics as constraints in the chain generation process .
      We have shown this algorithm to be computationally very efficient in generating
      large ensembles of candidate C(alpha) chains on the face centered cubic lattice,
      and illustrate its use by calculating a number of thermodynamic quantities
      related to protein folding characteristics. In particular, we have used this
      static MC algorithm to compare such temperature-dependent quantities as the
      ensemble mean energy, ensemble mean free energy, the heat capacity, and the mean
      square radius of gyration. We also demonstrate the use of several simple "guide
      fields" for introducing protein-specific constraints into the ensemble generation
      process. Several extensions to our current model are suggested, and applications
      of the method to other folding related problems are discussed.

PMID- 7578951
TI  - Applicability of a continuum solvation model to the octanol water transfer: CFF91
      based model for amino acids.
AB  - A continuum hydration model based upon the atomic charges provided with the CFF91
      force field [A. B. Schmidt and R. M. Fine (1994) Molecular Simulation, 13, 347
      365] has been extended to the octanol-water transfer. The electrostatic component
      of the transfer free energy is calculated using the finite-difference solution to
      the Poisson-Boltzmann equation while the nonpolar contributions are assumed to be
      proportional to the solute-excluded volume in water. All atomic charges and radii
      besides the aromatic carbon radius are equal in both solvents. The octanol
      dielectric constant and the probe radius are the main fitting parameters defining
      the octanol phase. The model has been tested for 38 organic molecules related to
      the amino acid residues and generally provides a high accuracy. In particular,
      the mean unsigned error for N-acetyl amino acid amides is 0.5 kcal/mol.

PMID- 7578952
TI  - Crystal structure and a twisted beta-sheet conformation of the tripeptide L
      leucyl-L-leucyl-L-leucine monohydrate trimethanol solvate: conformation analysis
      of tripeptides.
AB  - In order to test the helical preference of short oligo-L-leucines, we
      crystallized the tripeptide L-leucyl-L-leucyl-L-leucine (LLL) and carried out x
      ray diffraction studies of it (L-leucyl-L-leucyl-Lleucine)2. 3CH3OH. H2O,
      (C39H84N6O12), crystallized in the monoclinic system, space group P2(1), cell
      parameters: a = 12.031(2), b = 15.578(3), c = 14.087(2) A, alpha = 90 degrees,
      beta = 97.29(1) degrees, gamma = 90 degrees, V = 2618.6 A3, MW = 829.1, Dc =
      1.051 g cm-3, R index of 0.057 for 4213 reflections (lambda CuK alpha = 1.5418 A)
      > 2 sigma. LLL takes up the beta-sheet rather than a helical conformation in the
      crystalline state. The three methanol molecules and the water molecule that
      constitute the solvent of crystallization form a network of hydrogen bonds to the
      LLL molecules and to one another. It is rather remarkable that though A and L
      have stronger helical preferences than G, neither AAA nor LLL form the
      crystalline helix but GAL does, indicating that the helical preferences depend on
      the sequence context. The residue L2 in molecule A and the residues L1 and L3 of
      molecule B do not show the preferred conformation for forming helices. Further,
      very remarkably, LLL exhibits a unique supersecondary feature of the protein
      folding topology, namely the twisted beta-sheet, whereas most short peptides show
      only the classical beta-sheet conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578953
TI  - Crystal and molecular structure of the centrosymmetric meso-valinomycin analogue-
      cyclo (D-Val-D-Hyi-D-Val-L-Hyi-L-Val-D-Hyi-L-Val-L-Hyi-L-Val-D-Hyi-D-Val-L-Hy i)
      (C60H102N6O18).
AB  - The crystal structure of cyclo (D-Val-D-Hyi-D-Val-L-Hyi-L-Val-D-Hyi-L-Val-L-Hyi 
      L-Val-D-Hyi-D-Val-L-Hyi).2H2O has been solved by x-ray direct methods. The
      crystals (grown from a mixture of octane/CH2Cl2) are an orthorhombic,
      centrosymmetric space group Pbca, cell parameters a = 11.458 (2), b = 25.613 (3),
      c = 23.691 (3) A, Z = 4; therefore the molecule lies on a center of inversion in
      the cell. The atomic coordinates for the C, N, and O atoms were refined in the
      anisotropic thermal motion approximation (allowing for H-atom contribution to
      Fcal) to a standard R-factor value of 0.081. In contrast to meso-valinomycin, the
      analogue under study does not adopt an octahedral cage bracelet conformation. It
      has an unusual centrosymmetric elongated form with two type II terminal beta
      bends formed by N-H ... C=O 4-->1 type intramolecular H bonds. Two symmetry
      related water molecules reside in the elongated molecular cavity of the
      centrosymmetric depsipeptide ring.

PMID- 7578955
TI  - Effect of anisotropy of the bending rigidity on the supercoiling free energy of
      small circular DNAs.
AB  - In principle, the supercoiling free energy of a small circular DNA will be
      enhanced by increasing the anisotropy of its bending potential at constant
      persistence length. The magnitude of this effect is investigated by Monte Carlo
      simulation using an extension of a previously proposed algorithm. The
      supercoiling free energy at 298 K is simulated for circular DNAs containing N =
      bp with torsion constant alpha = 5.8 X 10(-12) dyne cm, persistence lengths P =
      500 A and 10,000 A, and a range of anisotropies of the bending potential from rho
      = 1.0 to 16.0. The apparent torsion constants, reckoned from these supercoiling
      free energies by assuming an isotropic bending potential, are found to increase
      by less than 3% as the input anisotropy increases from 1.0 to 16.0 When P = 500
      A, the apparent torsion constant never rises significantly above the input value
      over the entire range of input anisotropies. When P = 10,000 A, the apparent
      torsion constant rises only about 3% above the input value for anisotropies rho =
      8.0 and 16.0. Evidently, anisotropy of the bending potential cannot account for
      the fact that the torsion constants reported for small circular DNAs exceed those
      reported for long linear DNAs by a factor of 1.6 or more.

PMID- 7578956
TI  - Conformational studies of retro-inverso peptides: the crystal and molecular
      structure of the hydantoin from H-Ala-g-Ala-mGly-OBzl.
AB  - The crystal structure of the hydantoin 1-[(S)-1'-aminoethylmalonyl benzyl ester]
      (S)-4-methylimidazolidin-2,5-dione (1) derived from the peptide H-Ala-gAla-mGly
      OBzl, having the retro-inverso modification of the Ala-Gly bond, has been
      determined by x-ray diffraction analysis. The crystals are orthorhombic, space
      group P2(1)2(1)2(1) with a = 6.539, b = 14.721, c = 17.101 A, z = 4. The
      structure was solved by direct methods and refined with anisotropic thermal
      factors to a final R value of 0.067 for the 947 observed reflections. Reversal of
      the Ala-Gly amide bond perturbs the folding tendency of the backbone shown by the
      parent peptide t-BuCO-Ala-Gly-NHiPr. The gem-diamino residue, gAla, and the
      malonyl moieties are found in the helical and the extended conformations,
      respectively. Intramolecular hydrogen bonding is not observed. The molecules in
      the crystal are held together by the formation of two intermolecular hydrogen
      bonds of the N-H ... O=C type with N ... O distances of 2.86 and 3.17 A,
      respectively.

PMID- 7578957
TI  - A study of Na-DNA films containing NaCl via scanning electron and tunneling
      microscopies.
AB  - Unoriented films of Na-DNA were prepared by dessicating a gel with different
      amounts of NaCl. For low salt concentrations, the resulting films were smooth and
      patternless. For high salt concentrations, the resulting films had visible
      patterns that were very similar to those recently reported by Sclavi et al.
      [(1994) Biopolymers, Vol. 34, pp. 1105-1113]. Scanning electron and tunneling
      microscopies and electron dispersive spectroscopy studies were used to study the
      spatial distribution of NaCl throughout these films. Two main conclusions were
      reached about the NaCl: (1) some NaCl is distributed throughout every film, and
      (2) the visible patterns observed in films with a large amount of NaCl were
      caused by the growth of NaCl crystals during the dehydration process.

PMID- 7578954
TI  - Conformational study of linear alternating and mixed D- and L-proline oligomers
      using electronic and vibrational CD and Fourier transform IR.
AB  - Vibrational CD (VCD) spectra of a series of blocked linear, alternating D- and L
      proline containing oligopeptides, dissolved in D2O and in CDCl3, are reported.
      For the Boc-LDL-Pro3 to Boc-DLDLDLDL-Pro8 oligomers, the VCD spectra in the amide
      I band is a positive couplet, opposite in sense to that obtained for (L-Pro)n
      oligomers. While this admits the possibility of their favoring a right-handed
      helical chain conformation, the amide I ir spectra for these DL oligomers in D2O
      indicate a mixed, apparently alternate, cis-trans conformation that prevents a
      simple conclusion. Their VCD in D2O evidence no narrowing and has a progressive
      loss in intensity (measured as delta A/A) with an increase in chain length. In
      CDCl3 a similar pattern of positive VCD couplets decreasing in intensity with
      length was seen, but the ir spectra are narrower. Their electronic CD (ECD), in
      the uv, also indicates a loss in intensity with increasing length. Oligomers with
      odd or even numbers of Pro residues have different ECD patterns, indicating that
      those spectra are strongly influenced by local contributions arising in the N
      terminal groups. The VCD arises from dipolar and vibrational coupling of the
      amides in the helical structure. All the spectra are consistent with the chiral
      end groups leading to formation of an excess of one helical handedness. With an
      increase in length, the influence of this selectiveness is less and the overall
      CD measured decreases.

PMID- 7578959
TI  - Implantation and the endometrium.
AB  - Our knowledge relating implantation and the endometrium is largely descriptive at
      present. In the absence of a unifying hypothesis, I describe endometrial
      receptivity for implantation. Tissue component data are described, first relating
      to whole tissue, then isolated glands and stroma, vessels, the luminal
      epithelium, and infiltrating leukocytes. Finally, I consider trophoblast
      endometrial interaction. Stimulatory and inhibitory factors impinging on a
      proteolytic cascade must be related to the process of invasion of the
      trophoblast. Only early data are available, as the description of this
      fascinating process unfolds.

PMID- 7578958
TI  - Mapping epitopes on protein surfaces.

PMID- 7578960
TI  - Laparoscopic surgery: a real step forward, or tempting simply because possible
      and new?

PMID- 7578961
TI  - Endoscopy or the surgical revolution for women.

PMID- 7578964
TI  - Anaesthesiology.
AB  - Because of the extension of laparoscopic surgery to older patients with more
      complicated medical histories, anaesthetists increasingly have to face the
      problem of haemodynamic and respiratory tolerance of the technique. The
      management of such problems requires the understanding of the mechanisms
      involved, and their implications in terms of patient selection. Protocols where
      the maintenance of anaesthesia is provided using halogenated agents like
      isoflurane or desflurane have been shown to blunt the increase in systemic
      vascular resistances induced by CO2 insufflation and therefore enhance the
      haemodynamic tolerance of this procedure.

PMID- 7578962
TI  - Power sources in endoscopic surgery.
AB  - The power sources used in endoscopic surgery are varied and numerous, and will
      continue to improve as technology progresses. Early attempts at operative
      laparoscopy were crude, limited by the available instrumentation, and tended to
      be frustrating: scissors that had to be frequently sharpened and endocoagulators
      that took a seemingly interminable time to achieve their tissue effect. New
      developements in ultrasonic energy and different wavelengths of laser energy are
      used alongside increasingly sophisticated electrosurgical tools, employing both
      monopolar and bipolar systems, and innovative delivery systems such as the argon
      beam coagulator and the Helica Thermal Coagulator. All of these systems have
      their advocates and their detractors, but in the end the choice of power source
      is determined by the type of equipment that the operator feels most comfortable
      with. The surgeon must have a detailed knowledge of the physical concepts
      required to generate the power source, and be able to understand the
      complications that can be created by the energy, how to avoid them, how and to
      deal with them if they occur. Although there are subtle differences in the
      reaction of the different energy sources with human tissue, the clinical outcome
      appears to be much the same, and depends more on the skill of the individual
      surgeon than the power source employed.

PMID- 7578963
TI  - Complications of gynecologic laparoscopic surgery.
AB  - The growing impact of laparoscopic surgery must not make us underestimate the
      existence of complications, some of them severe, with medical-legal implications.
      Several surveys and case reports of complications following modern gynecologic
      laparoscopic surgery, some reporting laparoscopic management of visceral
      injuries, have been published recently. The complication rate depends on the
      complexity of the surgical procedure; serious complications still arise during
      performance of laparoscopy. Patients must be informed of the hazards of so-called
      'minimally' invasive surgery.

PMID- 7578965
TI  - The role of endoscopy in the management of the infertile patient.
AB  - As newer technologies are incorporated into the field of gynecologic surgery, we
      must know their limitations, and be able to ascertain their true efficacy with
      certainty. This is especially important when we make decisions with and for our
      patients, which may affect their future fertility. This review was written with
      this important goal in mind.

PMID- 7578966
TI  - Laparoscopic management of polycystic ovarian disease.
AB  - Laparoscopic treatment of polycystic ovary syndrome has its roots in bilateral
      wedge resection. Although it is still unclear why surgery is effective in
      treating this syndrome, more than 600 cases of patients treated laparoscopically
      have been reported in the literature. Recent publications enhance our
      understanding of appropriate patient selection as well as the effectiveness of,
      and the complications associated with, this procedure.

PMID- 7578967
TI  - Laparoscopic management of ectopic pregnancy.
AB  - Management of ectopic pregnancy includes a high index of suspicion coupled with
      established algorithms of diagnosis using serum beta-human chorionic gonadotropin
      and transvaginal ultrasound. Early diagnosis and intervention usually leads to
      conservation of the involved tube. Careful follow up for persistent ectopic
      pregnancy leads to appropriate medical or surgical management. The use of
      methotrexate, either systemically or by local injection, may provide an
      alternative to surgery in selected patients with ectopic pregnancy.

PMID- 7578968
TI  - Laparoscopic hysterectomy.
AB  - We describe the use of laparoscopic techniques in hysterectomy, and the
      epidemiology of hysterectomy. We review the advantages and complications of total
      laparoscopic hysterectomy and subtotal laparoscopic hysterectomy. Finally, we
      discuss long-term outcomes and the cost of these techniques.

PMID- 7578969
TI  - Endometrial ablation and resection.
AB  - Many hysterectomies for abnormal uterine bleeding can be avoided by the use of
      endometrial ablation or resection. Their role in older and postmenopausal
      patients has recently been emphasized. Complications, although infrequent, relate
      primarily to fluid intravasation or the inexperience of the surgeon. This cost
      effective technique should be offered to all appropriate patients.

PMID- 7578970
TI  - Laparoscopic oophorectomy.
AB  - Laparoscopic oophorectomy is one of the most controversial and challenging areas
      of endoscopic surgery. Judicious preoperative evaluation along with careful
      patient selection can reduce the risk of operating on an unsuspected ovarian
      malignancy. Appropriate patient consent and planning should be obtained before
      the procedure, in case an ovarian neoplasia should be encountered. Although
      endoscopic pelvic biopsy, treatment and staging has been reported recently, the
      standard of care still appears to be by a laparoscopy. The removal of benign
      cystic teratomas of all sizes can be handled laparoscopically with the assistance
      of a retrieval bag or pouch. Reports of endoscopic treatment of ovarian remnant
      syndrome, androgen insensitivity syndrome, and even prophylactic oophorectomy are
      appearing in the literature. They have major benefits to patients including
      reduced cost, decreased hospitalization and time away from work, and with similar
      or lower complication rates compared with other modes of treatment. Pelviscopy or
      operative laparoscopy is gaining in popularity and acceptance as our experience
      and training improves.

PMID- 7578971
TI  - Severe endometriosis and operative laparoscopy.
AB  - Laparoscopic surgery offers the most effective form of treatment for women with
      severe endometriosis. The development of advanced laparoscopic techniques allows
      complete removal of deeply infiltrating lesions. Implants can be laparoscopically
      dissected from all anatomical locations, including severe involvement of the
      ureter, bladder, and colon. When the endometriosis penetrates through the entire
      depth of the organ wall, complete resection and reanastomosis of the ureter or
      bowel can be safely performed laparoscopically by the experienced surgeon.
      However, optimal laparoscopic treatment requires not only surgical skill, but
      also comprehensive knowledge of pelvic anatomy and a good understanding of
      endometriosis and its progression.

PMID- 7578972
TI  - Laparoscopic lymphadenectomy.
AB  - Technical advances in operative laparoscopy are increasing its role in the
      management of gynecologic malignancies. The feasibility of both para-aortic and
      pelvic lymphadenectomies, as demonstrated in recent studies, have suggested that
      complete surgical staging of pelvic malignancies is not far away. We present a
      review of the progress made to date, and a view of where we need to go.

PMID- 7578973
TI  - Hysteroscopic myomectomy.
AB  - Transhysteroscopic myomectomy has proved to be safe and effective with
      experienced operators. The use of the continuous flow hysteroscope and
      preoperative monitoring of intrauterine pressure has contributed to the
      prevention of fluid intravasion accidents. Effectiveness has been demonstrated in
      a number of recently published long-term studies.

PMID- 7578974
TI  - Laparoscopic procedures for stress incontinence and prolapse.
AB  - Laparoscopic treatment of urinary stress incontinence and urogenital prolapse is
      a recent development. We describe the progress of the ideas and techniques, in
      this field. However, the literature lacks prospective randomized studies with
      sufficient follow up. So there is a need for these techniques, which seem
      attractive at first glance, to be fully assessed before they can be adopted as
      standard practice.

PMID- 7578975
TI  - Effects of calcium and exercise on bone mineral density in premenopausal women
      with osteoporosis.

PMID- 7578978
TI  - The modulation of IL-6 and TNF-alpha release by nitric oxide following
      stimulation of J774 cells with LPS and IFN-gamma.
AB  - Lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) induced nitric oxide
      synthase (NOS) activity, tumour necrosis factor-alpha (TNF-alpha), interleukin
      (IL)-6 and prostaglandin (PG)E2 release in J774 cells, a murine macrophage cell
      line. The role of endogenous NO in modulating TNF-alpha and IL-6 release was
      investigated using N-iminoethyl-L-ornithine (L-NIO), a specific inhibitor of NOS.
      L-NIO (10-1000 microM) produced a concentration-dependent potentiation of LPS and
      IFN-gamma induced IL-6 release. Time-course studies demonstrated a significant
      potentiation of IL-6 release at 12 h with a maximum effect at 48 h. By contrast
      to its effects on IL-6, L-NIO significantly attenuated TNF-alpha release, and at
      48 h reduced PGE2 release. The NO-donor S-nitroso-N-acetyl-penicillamine
      (SNAP,300 microM), significantly inhibited LPS and IFN-gamma induced IL-6
      release, but potentiated TNF-alpha release. In addition, SNAP prevented the
      potentiation of IL-6 and the inhibition of TNF-alpha release by L-NIO.
      Stimulation of J774 cells with a combination of LPS and IFN-gamma for 24 h or 48
      h reduced cell viability which was prevented by L-NIO. Furthermore, SNAP also
      reduced cell viability determined after 24 h incubation. These results indicate
      that NO can differentially modulate LPS and IFN-gamma-induced cytokine release
      from J774 cells, up-regulating TNF-alpha but down-regulating IL-6, and that NO is
      cytotoxic to these cells.

PMID- 7578976
TI  - Characterization of recombinant soluble human transforming growth factor-beta
      receptor type II (rhTGF-beta sRII).
AB  - Recombinant human transforming growth factor soluble receptor Type II (rhTGF-beta
      sRII) corresponding to the 159 amino acid extracellular domain of hTGF-beta RII
      has been expressed in insect cells using the baculovirus expression system or in
      a mouse myeloma cell line. N-terminal sequence analysis of the purified protein
      revealed the removal of the 23 amino acid signal peptide. In SDS-PAGE, the rhTGF
      beta sRII resolves into multiple bands due to N-linked glycosylation. Recombinant
      hTGF-beta sRII is a TGF-beta antagonist and will inhibit the biological
      activities of TGF-beta 1, TGF-beta 3, and TGF-beta 5 on TGF-beta-responsive cell
      lines, such as murine HT-2 or human TF-1 with an ED50 of approximately 0.3
      micrograms/mL. However, hTGF-beta sRII does not inhibit TGF-beta 2 bioactivities
      in these cell lines, suggesting that hTGF-beta RII has low affinity for TGF-beta
      2. Polyclonal antibodies to hTGF-beta sRII have been produced in goats and
      purified on Protein-G affinity columns. This antibody can inhibit TGF-beta
      1,2,3,5-dependent bioactivities on human cell lines such as TF-1. Additionally,
      this antibody has species cross-reactivity and will also inhibit TGF-beta
      dependent bioactivities on murine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578979
TI  - Interleukin 1 induces prostacyclin-dependent increases in cyclic AMP production
      and does not affect cyclic GMP production in human vascular smooth muscle cells.
AB  - Interleukin 1 (IL-1) is a pro-inflammatory cytokine which has direct vasorelaxant
      effects on vascular smooth muscle cells (VSMC). In the present study, IL-1
      markedly increased intracellular levels of the vasodilatory mediator, cAMP, in
      human saphenous and human aortic VSMC. IL-1-induced cAMP was associated with a
      marked increase in prostacyclin (PGI2) production, and was reversed by
      indomethacin and tranylcypromine, inhibitors of cyclooxygenase and PGI2
      synthetase respectively. Furthermore, PGI2, but not PGE2, was a potent inducer of
      cAMP production in HSVSMC, implicating a role for PGI2 in mediating IL-1-induced
      cAMP production. In previous studies, IL-1 increased immunoreactive cGMP
      production in human saphenous VSMC through a pathway inhibitable by soluble
      guanylate cyclase inhibitors, methylene blue and LY83583, but not by nitric oxide
      (NO) synthase inhibitors, suggesting a role of NO-independent activation of
      soluble guanylate cyclase. However, in the present study, it was found that cAMP
      cross-reacted significantly in cGMP radioimmunoassays employing three out of four
      commercial antisera, that IL-1 did not affect cGMP production in human saphenous
      or human aortic VSMC as determined by an RIA having low cAMP cross-reactivity,
      and that both LY83583 and methylene blue inhibited IL-1-induced increases in
      cAMP. The results implicate prostacyclin-dependent cAMP production as a mediator
      of the vasodilatory effects of IL-1 in humans.

PMID- 7578981
TI  - Changes in the expression of MCP-1 receptors on monocytic THP-1 cells following
      differentiation to macrophages with phorbol myristate acetate.
AB  - Human monocytic THP-1 cells were differentiated to macrophages by incubation with
      1.0 microM phorbol myristate acetate (PMA) for 1 to 18 h; cells were then assayed
      for the ability to migrate to MCP-1. In comparison to undifferentiated monocytes,
      the chemotactic response of PMA-differentiated cells to MCP-1 decreased with
      treatment time. This loss of the chemotactic response to MCP-1 correlated with
      increased in cellular enzymes characteristic of differentiated macrophages.
      Receptors binding assays demonstrated a parallel decrease in specific binding of
      MCP-1 with increased incubation with PMA. Undifferentiated monocytes had 1175 +/-
      387 receptors per cell with a Kd of 1.53 +/- 0.35 nM. Cells differentiated to
      macrophages with PMA rapidly lost the ability to bind MCP-1, with a significant
      decrease apparent following 3 h incubation with PMA. The reduction in specific
      binding of MCP-1 by M phi-THP-1 cells was due to a decrease in both receptor
      number and affinity; receptor number was reduced to 481 +/- 106 receptors/cells
      with a Kd of 3.16 +/- 0.7 nM on cells treated for 3 h with PMA. The demonstrated
      changes in receptor affinity and expression with differentiation may be a
      mechanism of controlling macrophage responsiveness to chemokines in inflammatory
      foci.

PMID- 7578980
TI  - IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting
      both transcription and MRNA stability.
AB  - The induction of cytokine expression in monocytes/macrophages by bacterial
      endotoxin or lipopolysaccharide is a critical, highly regulated host defence
      response. The augmentation of LPS responses by interferon gamma (IFN-gamma),
      referred to as priming, is well established. However, the mechanism(s) by which
      priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as
      a model, experiments were designed to analyse in detail the priming effect on the
      LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at
      the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the
      magnitude rather than the sensitivity of the LPS response. Priming occurred after
      several hours of treatment, and the primed state was induced by either IFN-gamma
      or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate
      than freshly isolated monocytes upon activation with LPS. The increased
      transcriptional rate correlated with a marked increase in nuclear factor-kappa B
      activity in these cells as determined by electrophoretic mobility shift assay
      using a consensus NF-kappa B oligonucleotide. An additional significant finding
      was than TNF mRNA induced in primed cells was much more stable than in unprimed
      cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability,
      the duration of mRNA accumulation was longer following LPS stimulation in primed
      monocytes, in addition to being of greater magnitude. Finally, primed and
      unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89.
      H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed
      cells, but had no effect on primed monocytes following LPS stimulation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7578977
TI  - Functional distinction of two regions of human interleukin 6 important for signal
      transduction via gp130.
AB  - Mutagenesis of a region of human interleukin (IL)-6 which is important for
      triggering signal transduction via the IL-6 receptor beta-chain (gp130) has lead
      to the isolation of a variant of human IL-6 (IL-6.Q160E/T163P), which could
      antagonize the biological activity of wild type IL-6 on the human EBV transformed
      B cell line CESS and the human hepatoma cell line HepG2. Surprisingly this
      antagonistic IL-6 variant had an agonistic effect on the human myeloma cell line
      XG-1, albeit at a 1000-fold higher concentration than wild type IL-6. This
      residual activity of the mutant arose from triggering gp130, because it could be
      inhibited by a gp130 specific mAb. Extensive mutagenesis of residues between Q153
      and H165 of human IL-6, a region which is partly homologous in cytokines which
      also signal via gp130 (oncostatin M, ciliary neurotrophic factor, leukaemia
      inhibitory factor, IL-11), did result in the isolation of a second antagonist for
      IL-6 activity on CESS and HepG2 cells. However on XG-1 cells this variant was
      active as well. These results suggest that (an) additional region(s) of the IL-6
      molecule might be involved in gp130 triggering. Recently we indeed found that
      residues Lys42-Ala57 are also important for gp130 triggering. Inhibition
      experiments with neutralizing IL-6R alpha-chain specific mAb show that this
      region can be functionally separated from the Q153-H165 region. These findings
      have important implications for the development of receptor antagonists of IL-6
      and IL-6 family members.

PMID- 7578982
TI  - Tumour necrosis factor-alpha induces morphological and functional alterations of
      intestinal HT29 cl.19A cell monolayers.
AB  - TNF-alpha is a widely distributed proinflammatory cytokine, involved in many
      disease states. Although it has widely distributed effects, a precise mechanism
      of action has never been described, in particular at the epithelial level. Morpho
      functional changes of the intestinal epithelial monolayer HT29 cl.19A exposed to
      TNF-alpha were therefore assessed, using electron microscopy (including freeze
      fracture replica analysis), as well as measurement of mannitol, Na+ and
      horseradish peroxidase fluxes across intestinal HT29 cl.19A cell monolayers using
      Ussing chambers. TNF-alpha receptors were induced on HT29 cl.19A cells by a small
      non-toxic dose of IFN-gamma (5 U/ml). After 4 h of the combined presence of TNF
      alpha (10 ng/ml) and IFN-gamma (5 U/ml), the tight junction structure was altered
      as shown by a significant decrease in the average strand number measured in the
      apico-basal direction (5.50 +/- 2.70 vs 3.73 +/- 1.39 in control and treated
      cells respectively, P < 0.0001) and by a significant decrease in junctional depth
      (0.27 +/- 0.14 and 0.17 +/- 0.10 microns in control and treated cells
      respectively, P < 0.0001). These results are in agreement with a decrease in
      number of 'kiss' sites between contiguous membranes of TNF-alpha treated cells
      observed in ultrathin sections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7578983
TI  - Transcriptional upregulation of TGF-alpha by phenylacetate and phenylbutyrate is
      associated with differentiation of human melanoma cells.
AB  - The aromatic fatty acids phenylacetate (PA) and phenylbutyrate (PB) induce tumour
      cell differentiation in experimental models and both are currently in clinical
      trials. The purpose of this study was to determine the effect of these antitumour
      agents on the expression of transforming growth factor-alpha (TGF-alpha) in
      neoplastic cells. Treatment of human melanoma 1011 cultures with either PA or PB
      caused over 40-fold increase in TGF-alpha biosynthesis and secretion into the
      media. Whereas elevation in TGF-alpha mRNA steady-state levels became evident
      within 6-12 h and reached peak quantities the following day, the amounts of its
      coded protein increased gradually over a period of 5 days of treatment. Further
      molecular analysis revealed that regulation of TGF-alpha expression occurred at
      the transcriptional level. In contrast to TGF-alpha, expression of its receptor
      remained below detectable levels, indicating that an autocrine loop involving
      this growth factor is unlikely. Interestingly, the increase in TGF-alpha
      production paralleled drug-induced cytostasis and differentiation defined by
      morphological changes and increased melanogenesis. Like PA and PB, other
      differentiation inducers such as all-trans-retinoic acid, dimethyl sulfoxide, and
      5-aza-2'-deoxycytidine, all induced TGF-alpha expression in the melanoma cells.
      The close association between enhanced TGF-alpha production and melanoma cell
      differentiation suggests that this growth factor, often linked to mitogenesis,
      may play a novel role in tumour differentiation by PA and PB.

PMID- 7578984
TI  - Evidence for exclusive role in signalling of tumour necrosis factor p55 receptor
      and a potentiating function of p75 receptor on human endothelial cells.
AB  - The current study was undertaken to investigate the role of TNF-R75 in regulation
      of E-selectin and ICAM-1 expression by TNF on HUVEC. To this end, we used
      agonistic anti-TNF-R75 antibodies, being mAb MR2-1 and polyclonal antibodies anti
      TNF-R75 (pAb75). The agonistic properties of these antibodies were ascertained by
      the costimulatory capacity in a T-cell proliferation assay. These anti-TNF-R75
      antibodies bound effectively to HUVEC, as evidenced in binding studies using 125I
      TNF, but they did not induce or enhance E-selectin or ICAM-1 expression as did
      agonistic anti-TNF-R55 antibodies. In contrast, both MR2-1 and pAb75 inhibited
      specifically TNF-induced E-selectin and ICAM-1 expression, but not activation by
      IL-1 or LPS. These results support the hypothesis, that in cells responding to
      TNF via the signalling pathway of the TNF-R55, the extracellular part of TNF-R75
      captures TNF and delivers it to TNF-R55, resulting in an enhanced response to
      TNF.

PMID- 7578985
TI  - Cytotoxicity in L929 murine fibrosarcoma cells after triggering of transfected
      human p75 tumour necrosis factor (TNF) receptor is mediated by endogenous murine
      TNF.
AB  - We compared the biological function of the human tumor necrosis factor receptors
      p55 (hTNF-R55) and p75 (hTNF-R75) expressed in the murine (m) fibrosarcoma cell
      line L929. Receptor-specific triggering of hTNF-R55 in transfected L929 cells by
      agonistic monoclonal antibodies or hTNF-R32WS86T, a hTNF-R55-specific mutant of
      hTNF, resulted in cytotoxicity. Specific clustering of hTNF-R75 in transfected
      L929 cells by agonistic monoclonal antibodies or hTNF-D143F, a hTNF-R75-specific
      mutant of hTNF also induced cytotoxicity, albeit at low level. In both cases, the
      cytotoxic activity of receptor clustering could be synergized by addition of 20
      mM LiCl. Remarkably, cytotoxicity induced after R75 triggering in transfected
      L929 cells could be completely abolished by addition of neutralizing anti-mTNF
      antibodies, in contrast to cell killing seen after specific R55 clustering. No
      soluble mTNF could be demonstrated using a sensitive biological assay, although
      L929 cells were expressing low levels of mTNF-specific mRNA as shown by PCR.
      These data clearly demonstrate that minute amounts of endogenously produced TNF
      can be a key mediator in R75-mediated cytotoxicity. Presumably, the latter
      efficiently traps the ligand and transfers it to TNF-R55, and/or by binding it,
      protects the endogenously made TNF from inactivation.

PMID- 7578986
TI  - Evaluation of GM-CSF mouthwash for prevention of chemotherapy-induced mucositis:
      a randomized, double-blind, dose-ranging study.
AB  - Uncontrolled clinical trials have shown that parenteral administration of GM-CSF
      reduces the frequency of chemotherapy-induced mucositis. The mechanism of this
      effect could be related to acceleration of haematopoiesis and/or increase in
      functional activation of WBC. We conducted a double-blind, placebo-controlled,
      dose ranging study of GM-CSF (mol-gramostim) mouthwash in patients with breast
      cancer during the first treatment cycle of a combination chemotherapy regimen
      which has historically produced dose-limiting (grade > or = 3) mucositis in
      approximately 39% of patients. Subjects were randomized to receive either placebo
      mouthwash (0.1 percent albumin) or one of four concentrations of GM-CSF mouthwash
      (0.01, 0.1, 1.0 or 10 mcg/ml). The primary endpoint was to evaluate the
      relationship between dose of GM-CSF mouthwash received and probability of grade >
      or = 3 mucositis using a logistic model. Solutions were administered four times
      daily starting within 24 hours of chemotherapy initiation and continuing until
      the end of the cycle (day 21). Mucositis was assessed on days 1-6, 10, 15 and 21.
      Day 6 plasma samples were assayed for GM-CSF. Forty-five patients were evaluable
      for response (nine per dosing group). A 42% risk (15/36) of mucositis grade > or
      = 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9
      patients on the placebo arm. No evidence of dose response was found by logistic
      regression. Five patients had a detectable plasma concentration of GM-CSF (56-209
      pg/ml). A positive correlation between GM-CSF dose and leukocyte recovery was
      noted (P = 0.04).

PMID- 7578987
TI  - PCR analysis of interleukin-1 receptor gene in the nonobese diabetic mouse.
AB  - Insulin-dependent diabetes mellitus (IDDM) is characterized by a progressive
      autoimmune destruction of pancreatic beta cells. Many data suggest that
      interleukin 1 (IL-1) plays a fundamental role in the pathogenesis of the disease.
      In the nonobese diabetic (NOD) mouse, a spontaneous model of IDDM, it was put
      forward that the disease is linked to a susceptibility locus, called idd5, which
      contains the IL-1 receptor (IL-1R) gene. The polymerase chain reaction (PCR) was
      used to characterize the IL-1R gene in our NOD mouse colony and in two mouse
      strains taken as controls. Using primers to amplify the IL-1R gene between bp-106
      and +378, a 580 bp fragment was obtained from C57BL/6 DNA but not from DBA/2 and
      NOD DNA. However, amplification of the IL-1R gene region between bp +1 and +378
      in the three strains yielded amplicons 480 bp long. The specificity of the
      amplification was confirmed by restriction analysis. Our results suggest,
      depending on the strain, the presence of one or two introns: one (480 bp) in the
      5'-untranslated region and the other (100 bp) in the region coding for amino
      acids between 69 and 126, and an exon-intron organization of the mouse IL-1R gene
      different than that described in the human genome.

PMID- 7578988
TI  - Hemozoin differentially modulates the production of interleukin 6 and tumor
      necrosis factor in murine malaria.
AB  - When murine peritoneal macrophages were loaded in vitro with Plasmodium vinckei
      hemozoin and stimulated for 24 hours with interferon-gamma and/or Escherichia
      coli lipopolysaccharide, the production of interleukin 6 (IL-6) was drastically
      reduced, whereas the secretion of tumor necrosis factor (TNF) was increased. In
      addition, non-radioactive in situ hybridizations in spleen sections of P. vinckei
      infected mice showed more TNF than IL-6 gene expression in the red pulp around
      hemozoin accumulation. These results provide evidence that IL-6 and TNF are
      differentially modulated by hemozoin and that subsequently, the secretion of IL-6
      seems to be independent of the TNF production during murine malaria.

PMID- 7578989
TI  - Effects of pentoxifylline on human polymorphonuclear neutrophil responses to TNF
      in whole blood.
AB  - We used flow cytometry to study the effects of pentoxifylline (PTX) on the
      expression of adhesion molecules and fMLP receptors on whole-blood
      polymorphonuclear neutrophils (PMN) in response to TNF, together with the
      oxidative burst and actin polymerisation. This technique analyses cells
      individually and avoids PMN activation related to isolation procedures. PTX
      reduced CD11b upregulation induced by TNF. Moreover, PTX reduced both TNF-induced
      binding of bacterial formyl peptides (fMLP) by human PMN and TNF priming of the
      PMN oxidative burst in response to these peptides. PTX also reduced TNF-induced
      actin polymerisation, which has been reported to participate in receptor cycling.
      This phenomenon could account in part for the ability of PTX to reduce fMLP
      binding to the PMN surface and subsequently to inhibit the PMN oxidative burst in
      response to fMLP. In addition to the PTX-induced decrease of TNF production,
      these effects on PMN could be beneficial in pathological conditions where high
      TNF production may induce excessive PMN activation, leading to vascular damage
      and tissue injury.

PMID- 7578991
TI  - The impact of cytokines on high dose chemotherapy followed by transplantation of
      purified and ex vivo expanded peripheral blood stem cells: achieving a state of
      minimal residual disease for tumor immunotherapy with cytokine gene transfected
      cells.

PMID- 7578990
TI  - Ubiquitous interleukin-1 alpha in fetal bovine serum may mislead the experimental
      results in vitro.
AB  - Fetal bovine sera (FBS) from several commercial suppliers were fractionated by
      gel filtration. Interleukin-1 (IL-1) activity was bioassayed using the IL-1
      specific murine T cell line D10(N4)M. All the sera examined contained IL-1-like
      activity, with molecular weights (M(r)) of 30 kDa and 15-10 kDa. Under
      isoelectric focusing (IEF), the majority of IL-1 activity in either 30 kDa or 15
      10 kDa fractions was focused into a position of pl 5. The activity recovered from
      either IEF or gel filtration was inhibited by either recombinant human IL-1
      receptor antagonist (rhlL-1ra) or by the antibody against human IL-1 alpha. These
      biological and physicochemical properties strongly suggest that the active
      molecules were bovine IL-1 alpha and its precursor. There was no correlation
      between the amount of endotoxin and IL-1 activity. Quantification of the
      fractionated IL-1 indicated its presence in concentrations of 200-5000 pg/ml
      equivalent to human IL-1. However, high levels of IL-1 were not apparent in
      unfractionated FBS. Proliferation of T cells in the presence of FBS absorbed with
      protein A-Sepharose was greater than that of cells in original FBS. Therefore,
      the activity in FBS as a whole appeared to result from the balance between IL-1
      and the inhibitory molecule(s). These results suggest that data obtained from
      experiments conducted in the presence of FBS may be influenced by the effect of
      bovine IL-1.

PMID- 7578994
TI  - Trends in mortality and hospital morbidity due to abdominal aortic aneurysms.
AB  - This article examines national and regional trends in mortality and morbidity due
      to abdominal aortic aneurysms from 1969 to 1991. Annual age-adjusted mortality
      and hospital separation rates were calculated for men and women aged 55 and older
      whose underlying cause of death was abdominal aortic aneurysm, or who were
      hospitalized with a primary diagnosis of abdominal aortic aneurysm. In recent
      decades, abdominal aortic aneurysm mortality rates remained stable, in contrast
      to substantial declines in mortality rates for cerebrovascular disease and
      cardiovascular disease. The pattern was similar for both sexes, although rates
      were four to five times higher among men than among women. In 1991, age-adjusted
      rates were around 31.0 per 100,000 men aged 55 and over and 8.5 per 100,000 women
      aged 55 and over. Over the 1969 to 1991 period, mortality rates in all regions
      tended to converge. Although mortality rates were stable, hospital separation
      rates for abdominal aortic aneurysms increased sharply, particularly for
      unruptured aneurysms. Screening programs have been able to detect asymptomatic
      abdominal aortic aneurysms, and surgical intervention can substantially reduce
      mortality. However, the costs and benefits of screening programs should be
      assessed. If current mortality rates persist, as the baby boom ages there will be
      an absolute increase in the number of deaths from abdominal aortic aneurysms.

PMID- 7578992
TI  - Mechanisms of action of the tumor necrosis factor and lymphotoxin ligand-receptor
      system.
AB  - In the past few years, a number of experimental observations have provided more
      insight into the mechanisms of action of tumor necrosis factor (TNF)/lymphotoxin
      (LT) ligand-receptor system. This system consists of three ligands, TNF, LT alpha
      (LT alpha) and LT beta (LT beta), and three membrane-associated receptors, p55,
      p75 and LT beta-receptor (LT beta-R). Like TNF, LT alpha is a secreted protein
      which in solution forms a homotrimer molecule, with a conformation similar to
      that of TNF. LT beta is a transmembrane protein that provides the membrane anchor
      for the attachment to the cell surface of the heteromeric complex of LT alpha and
      LT beta. This complex retains a structure related to TNF and LT alpha
      homotrimers, with the homology regions interacting in a heterotypic fashion. The
      LT alpha 1:LT beta 2 heteromer has been found to be a predominant form of surface
      LT. The biological effects of TNF and LT alpha homotrimers are mediated by p55
      and p75 receptors, while the heteromeric complex of LT alpha/LT beta transduces
      its cellular signal via LT beta-R. Membrane-associated receptor affinities as
      well as final biological effects of TNF/LT can be modulated by the influence of
      naturally occurring soluble receptors, derived from the cell surface by
      proteolytic cleavage. The multimerization of receptor cytoplasmic domains upon
      TNF/LT ligation is postulated to activate the intracellular signal-transduction
      pathways. One of them is the activation of phospholipase A2 (PL-A2) resulting in
      the production of arachidonic acid (AA) and other metabolites, including
      leukotriens, phosphatidycholine-specific phospholipase C (PC-PLC) with subsequent
      production of diacylglycerol (DAG) and activation of protein kinase C (PKC). As a
      third signaling pathway, TNF/LT employ the sphingomyelinase (SMase)-mediated
      hydrolysis of membrane sphingomyelin (SM) to ceramide. The final link in the
      TNF/LT signaling is activation of nuclear transcription factors, such as NF-kappa
      B, AP-1, interferon regulatory factors-1 and -2 (IRF-1, IRF-2), and NF-GMa. Since
      induction of AP-1, IRF-1 and IRF-2 as well as NF-GMa proceeds through
      translational event, the posttranslational TNF/LT-driven activation of NF-kappa B
      remains the only cellular event identified so far that serves as a direct target
      in their signaling cascade.

PMID- 7578996
TI  - Trends in hospital utilization, 1982-83 to 1992-93.

PMID- 7578993
TI  - Regulation of T cell receptor gamma gene expression by cytokines in murine
      hematopoietic cells.
AB  - Murine IL-3-dependent myeloid cell lines express transcripts from non-rearranged
      TCR gamma genes and this expression is dependent upon IL-3. To investigate this
      observation in general terms we examined various IL-3 dependent cell lines for
      TCR gamma gene expression. We also examined various cytokines to test their
      potential to induce TCR gamma gene expression. All IL-3 dependent cell lines
      expressed TCR gamma transcripts. The IL-3 induced expression was sensitive to
      protein synthesis inhibitors. This demonstrated that the TCR gamma genes belong
      to the early growth factor response class. IL-3, IL-4, GM-CSF and Erytropoietin
      (EPO), but not G-CSF, induced TCR gene expression. 32D cells transfected with the
      IL-2 beta chain receptor became responsive to IL-2 as a growth factor and induced
      TCR gamma gene expression. The induction of TCR gamma gene expression by the
      cytokines was not correlated to their growth promoting activity. This indicated
      different signaling pathways.

PMID- 7578997
TI  - Deaths 1993.

PMID- 7578998
TI  - Impact of new population estimates on health and vital statistics.
AB  - Changes in Statistics Canada's annual population estimates, introduced in 1993,
      have an impact on a wide range of social, economic and demographic indicators.
      Any indicator that relies on population estimates will be affected by the new
      figures. This article describes the adjustment and examines its impact on health
      and vital statistics rates. With rare exceptions, all rates decrease as the
      denominators are adjusted upward. For example, accident rates, suicide rates, and
      age-specific fertility rates based on the adjusted population are lower than
      those previously calculated. The extent of the adjustment, however, depends on
      the geographic and demographic characteristics of the population at risk.
      Analysts whose work concentrates on special subgroups for whom the adjustment is
      particularly great (such as young adult men) may wish to pay closer attention to
      the new population figures. Although the new rates are lower than before,
      underlying trends and patterns over time or across subcategories are quite
      similar. The revised series incorporates estimates of net census undercoverage,
      and for the first time, includes non-permanent residents. In 1991, net census
      undercoverage and non-permanent residents together amounted to about one million
      persons, or 3.6% of the revised Canadian population of 28,120,100.

PMID- 7578999
TI  - Relations of hormones and growth factors at the crossroad of pathogenesis and
      pharmacotherapeutics. The case of diabetes mellitus.

PMID- 7578995
TI  - Sample design of the national population health survey.
AB  - In 1994, Statistics Canada began data collection for the National Population
      Health Survey (NPHS), a household survey designed to measure the health status of
      Canadians and to expand knowledge of health determinants. The survey is
      longitudinal, with data being collected on selected panel members every second
      year. This article focuses on the NPHS sample design and its rationale. Topics
      include sample allocation, representativeness, and selection; modifications in
      Quebec and the territories; and integration of the NPHS with the National
      Longitudinal Survey of Children. The final section considers some methodological
      issues to be addressed in future waves of the survey.

PMID- 7579000
TI  - Antipyrine, coumarin and glipizide affect n-acetylation measured by caffeine
      test.
AB  - The effect of various treatments on acetylation status measured by caffeine
      metabolites was investigated in 17 subjects with non-insulin dependent diabetes
      mellitus (NIDDM). The test drugs, caffeine (200 mg), antipyrine (20 mg/kg) and
      coumarin (5 mg), were given simultaneously, and urinary 5-acetylamino-6-formyl
      amino-3-methyluracil/1-methylxanthine (AFMU/1X) molar ratio was measured before
      and after 8 weeks of therapy. The urinary AFMU/1X molar ratio decreased (p <
      0.05) after 8 weeks of therapy with glipizide (2.5 mg), but remained unaltered in
      those treated with placebo or those who self-monitored blood glucose (SMBG) by
      glucometer. Antipyrine and coumarin decreased (p < 0.05) the AFMU/1X molar ratio
      both in diabetics and healthy volunteers. Our data demonstrate that glipizide,
      antipyrine and coumarin may interfere with the classification of acetylator
      status measured by caffeine metabolites.

PMID- 7579002
TI  - New approaches for treatment in diabetes: aldose reductase inhibitors.

PMID- 7579001
TI  - A decreased metabolic clearance of glucose is involved in the hyperglycemic
      effect of a serum temperature induced factor (TIF).
AB  - We have studied the effects of a hyperglycemic temperature induced factor (TIF)
      on glucose metabolism, in 3 groups of Wistar rats: 10 rats injected with non
      heated serum, 10 rats injected with heated serum and 10 rats injected with semi
      purified TIF. Seric levels of insulin and glucagon were not modified in rats
      injected with heated serum. The injection of heated serum induced hyperglycemia
      (p < 0.0001), a decrease of lactate (p < 0.001) and pyruvate (p < 0.05) levels,
      and an increase of acetoacetate level (p < 0.001). The levels of beta
      hydroxybutyrate and amino acids (alanine and glutamine) were not changed. Glucose
      turn over rate (12.3 +/- 1.3 g/min/kg) and metabolic clearance of glucose (10.0
      +/- 0.8 ml/min/kg) were significantly lower in rats treated with heated serum and
      purified TIF than in controls (respectively, p < 0.05 and p < 0.001). These data
      suggested that the hyperglycemic effect of heated serum and isolated TIF could
      correspond to an impaired metabolic clearance of glucose and to an increased
      gluconeogenesis.

PMID- 7579003
TI  - Deantigenation of human type B erythrocytes with Glycine max alpha-D
      galactosidase.
AB  - Conversion of erythrocyte membrane B antigen to H antigen produces blood type O
      which is universally transfusable. If efficient large-scale production of
      enzymatically converted red blood cells is to be achieved, then optimal
      conditions for deantigenation must be determined. Cell suspension assays were
      used to study the blood group B activity of Glycine max (soybean) alpha-D
      galactosidase on native human erythrocytes. The enzyme readily hydrolyzed the
      terminal alpha-D-galactosyl residue of the B antigen, converting it to H antigen.
      Optimal conditions for the enzymatic conversion of red cells with the Glycine
      enzyme are described. Normal cell morphology and function were maintained under
      optimal conditions.

PMID- 7579004
TI  - The cytotoxicity of N-Pyridinyl and N-quinolinyl substituted derivatives of
      phthalimide and succinimide.
AB  - The N-pyridinyl and N-quinolinyl substituted derivatives of phthalimides and
      succinimides demonstrated cytotoxicity against the growth of a number of cultured
      cell lines. The substituted succinimides were more effective than the
      unsubstituted succinimide derivative in reducing cell growth. On the other hand,
      phthalimide demonstrated more potent cytotoxicity than its N-substituted
      derivatives. Three representative examples N-[2-pyridinyl-1-oxide) methyl]
      phthalimide 8, 1-[N-2-phthalimidoethyl]-3,4-dihydroiso-quinoline 12, and 1-[N-(2
      (1,2,3,4-tetrahydro-2-quinolinyl)] ethylphthalimide 14 were shown to inhibit
      L1210 leukemia DNA synthesis whereas RNA synthesis was not inhibited at 25-100
      uM. All three agents inhibited the activities of DNA polymerase alpha, PRPP-amido
      transferase, nucleoside kinases, and dihydrofolate reductase. The cellular pool
      levels of d[GTP], d[CTP], and d[TTP] were reduced after 60 minutes incubation at
      100 uM. The DNA molecule itself was not a target of these agents.

PMID- 7579005
TI  - Comparison of serum total sialic acid, C-reactive protein, alpha 1-acid
      glycoprotein and beta 2-microglobulin in patients with non-malignant bowel
      diseases.
AB  - Total sialic acid (TSA), C-reactive protein (CRP); alpha 1 acid glycoprotein
      (alpha 1-AG), and beta 2-microglobulin were determined in 84 patients affected by
      non-malignant intestinal diseases, Crohn's disease (CD) and ulcerative colitis
      (UC), active and in remission; non-ulcerative proctosigmoiditis; diverticulosis;
      diverticulitis (ie, inflammatory complication of diverticulosis). Only in
      patients with acute phase CD, TSA was statistically higher than those in
      remission, as well as in controls. In patients with acute CD and in those with
      diverticulitis, CRP was significantly higher than in the controls. alpha 1-AG was
      found significantly increased in acute UC and CD patients versus the respective
      groups in remission, as well as versus controls. Moreover, alpha 1-AG was higher
      in patients with diverticulitis. beta 2-microglobulin did not differ in any group
      of patients. In five patients with CD in acute phase, investigated before and
      during the pharmacological treatment (5-aminosalycilic acid and steroids), CRP
      values fell into the normal range after the second week of therapy, whereas TSA
      values reached the higher limit of the normal range after the third week, except
      for two CD patients with a larger location (ileocolonic) of the disease. The
      results are briefly discussed.

PMID- 7579006
TI  - Whole body hyperthermia associated with beta-carotene supplementation in patients
      with AIDS.
AB  - The objective of this work was to check possible additive beneficial effects of
      whole body hyperthermia (WBH) associated with beta-carotene (BC) supplementation
      in patients with AIDS. In a pilot study, 10 HIV positive patients, (8 with AIDS
      and 2 with AIDS related complex, ARC), after AZT or DDI discontinuation, were
      first treated with one single session of WBH applied with a non-invasive
      procedure at 42 degrees C core temperature for one hour, and subsequently
      supplemented with BC 120 mg daily continuously. All patients well tolerated the
      non-invasive WBH as well as the high dose BC supplementation. Apart from one
      patient who died after 4 months, all the others underwent an HIV burden
      diminution, clinical improvement and amelioration of laboratory data, along with
      an subjective improvement of their life quality. With reference to control
      groups, namely (a) only WBH applied with extracorporeal procedure to 31 AIDS
      patients, and (b) only BC supplementation at high dosage applied to 64 ARC
      patients, the combined physical and BC supplemental treatments clearly showed a
      better and longer lasting response.

PMID- 7579007
TI  - Effects of an aldose reductase inhibitor, epalrestat, on diabetic neuropathy.
      Clinical benefit and indication for the drug assessed from the results of a
      placebo-controlled double-blind study.
AB  - The clinical efficacy of epalrestat (150 mg/day, 50 mg tid, po; A group), an
      aldose reductase inhibitor, was evaluated in 196 patients with diabetic
      neuropathy by a double-blind study using placebo (9 mg/day, 3 mg tid, po; P
      group) as a control for 12 weeks. The disappearance rates of upper limb
      spontaneous pain were 42.9% and 12.0% in the A and P groups, respectively, and
      those of lower limb spontaneous pain 48.6% and 22.6%, thus being significantly
      higher in the A group (p < 0.05, logrank-test). The motor nerve conduction
      velocity of the peroneal nerve significantly increased only in the A group (delta
      1.6 +/- 0.6 m/sec, p < 0.01, paired t-test), and the extent of increase in that
      of the median nerve was significantly greater in the A group than in the P group
      (p < 0.05). Thresholds of vibratory sensation and autonomic nerve function were
      also significantly improved in the A group (p < 0.05). The data were reanalyzed
      by dividing patients into two groups according to their HbA1c values. The
      improvement ratings of subjective symptoms and of nerve function tests for cases
      with HbA1c > or = 7.5% were both significantly different between the A and P
      groups, with the improvement rate being higher in the A group, and also higher as
      compared to the analysis for cases with HbA1c < 7.5%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579008
TI  - Intensive insulin therapy in insulin-dependent diabetes mellitus, the results of
      the diabetes control and complications trial.
AB  - Long term complications are the first causes of mortality and morbidity in
      diabetic patients. In Europe, many diabetologists speculated for a long time that
      a tight blood glucose control was the best way to avoid these complications, but
      without any complete evidence. In 1993, the results of the Diabetes Control and
      Complications Trial (DCCT), the first controlled, randomized, long term trial
      designed to study the link between metabolic control and complications in a large
      cohort of patients, has confirmed this hypothesis: in insulin-dependent diabetes
      mellitus, intensive insulin-therapy, as compared with conventional therapy,
      significantly reduces the risk of developing microvascular and neuropathic
      complications. Nevertheless, in some patients, the risk of hypoglycemia may
      outweight the benefit of intensive insulin therapy, and the results of the DCCT
      raises some questions about indications, the risk/benefit ratio and the
      cost/benefit ratio of intensive treatment.

PMID- 7579009
TI  - Plasma beta-endorphin levels and glucose tolerance in patients with chronic renal
      failure.
AB  - In order to examine the role of endogenous opioid peptides on glucose metabolism
      in uraemic patients, plasma concentrations of beta-endorphin, glucose, insulin
      and C-peptide were determined before and during an oral glucose tolerance test
      (OGTT) in nine non-dialysed patients with chronic renal failure (CRF). The
      results are compared with those obtained in a group of age-matched normal
      subjects. In CRF patients, plasma beta-endorphin fasting values (16.0 +/- 1.9
      pmol/l) were significantly higher than those of the controls (6.6 +/- 0.6 pmol/l)
      and significantly correlated with the degree of renal function impairment. After
      glucose load, plasma beta-endorphin in CRF patients tended to decline, whereas in
      normal subjects increased. The fasting and the mean OGTT plasma beta-endorphin
      values negatively correlated with insulin initial response to glucose, insulin
      and C-peptide mean OGTT values, but not with glucose OGTT mean values. Data
      indicate that chronic uraemia induces a significant increase in circulating
      plasma beta-endorphin levels, with a loss of opioid system responsiveness to
      glucose. The possibility that this hyper-endorphinism may have a biological
      importance at least as a contributory factor of impaired glucose tolerance in
      uraemia may be suggested.

PMID- 7579010
TI  - Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile
      autism.
AB  - The serum tryptophan to large neutral amino acids ratio (Try/LNAA) is considered
      a reliable marker of tryptophan availability for brain serotonin synthesis. A
      dysfunction of brain serotonergic activity has been postulated to exist in
      autistic disorder and supported by recent studies. On this basis, we determined
      the serum amino acids levels in 40 children with idiopathic infantile autism as
      well as in 46 control children. A significantly lower serum Try/LNAA ratio was
      observed in the autistic subjects compared to the normal controls. In 14 autistic
      children (35%) this ratio was 2 SD below the mean value obtained in the control
      group. These results suggest that a low brain tryptophan availability due to a
      low serum Try/LNAA ratio could be one of the possible mechanisms involved in the
      alteration of serotonergic function in autism.

PMID- 7579011
TI  - Bone marrow cells as cytostatic effectors responsible for suppressing leukemia
      growth in vitro.
AB  - When bone marrow (BM) cells, isolated from normal (C57BL/6 x DBA/2)F1 mice (H
      2b/H-2d), were cultured with leukemic cells for 24 hours, a significant tumor
      growth suppression, without noticeable tumor cell killing, was found. The level
      of BM cell-mediated cytostasis of both P815 mastocytoma (H-2d) and L1210 lymphoma
      (H-2d) cells was dependent on BM-to-tumor cell ratio; 100% growth inhibition was
      obtained at a ratio of 480/1. In addition, BM cells were found to be able to
      synergize in suppressing P815 cell growth with lymphoid cells. The synergistic
      suppressive effects on tumor cell proliferation were observed in BM-spleen, BM
      thymus and BM-lymphnode cell co-cultures. The analysis of cytostatic activity of
      the cell culture supernatants showed that the synergistic leukemia growth
      suppression could be mediated, at least in part, by cell-derived soluble
      cytostatic molecules. The data presented herein also indicated that culturing BM
      cells with either crude supernatant (25%) from allogeneic mixed lymphocyte
      culture (MLC) or recombinant human interleukin(IL)-2 (20 U/ml) for 20 hours led
      to a 2-fold increase in their cytostatic activity against both P815 and L1210
      cells. Taken together, the results suggest that although normal BM cells are
      ineffective in tumor cell killing, they may play an important role in cell
      mediated effector mechanisms responsible for suppressing leukemia development;
      and that activated T lymphocytes, through producing cytokine(s), may rapidly
      upregulate leukemia growth inhibitory activity of BM cells.

PMID- 7579012
TI  - Lymphocyte ultrastructure in patients with multiple sclerosis.
AB  - The present study was undertaken to examine the ultrastructure of the lymphocytes
      of patients with relapsing-remitting multiple sclerosis (RRMS) and to compare it
      to that of the lymphocytes of multiple sclerosis (MS) patients treated with
      intravenously administered immunoglobulin 0.4 mg/kg of body weight for 5
      consecutive days followed by booster doses of immunoglobulin 0.4 mg/kg every two
      months for a total of 12 months. Peripheral blood lymphocytes of healthy
      volunteers served as control. The results indicate that lymphocytes of untreated
      patients differ markedly by both ultrastructure, as well as the number and size
      of their mitochondria. Since most of these changes disappeared following
      treatment, it is suggested that they are an expression of lymphocyte activation
      in this disease.

PMID- 7579013
TI  - Proteolytic activity in extracts of invasive cervical carcinoma and precursor
      lesions.
AB  - In this preliminary report, we showed that proteolytic activity of extracts from
      85 cervical samples of patients with normal cervix, low and high-grade squamous
      intra-epithelial lesions and invasive carcinoma, increased according to the
      natural history of the cervical cancer when measured with three different
      substrates. Inhibitor assays for four different catalytic classes of
      endopeptidases indicated that the predominant catalytic class in extracts of all
      groups was that of metalloproteinases. Substrate gel electrophoresis revealed
      that invasive carcinoma extracts had two bands with proteolytic activity (with
      M(r) of 72 and 52 kDa) which were not present in normal tissue or biopsies with
      precursor lesions. Immunological and molecular characterization of these bands
      may provide information relevant to cervical cancer biology and clinical
      applications.

PMID- 7579014
TI  - What provision is made by practicing physicians for psychogeriatric patients in
      western Germany?
AB  - This study examined some aspects of psychogeriatric care in Munster, Germany. The
      diagnostic and therapeutic attitudes of 94 general practitioners/internists and
      neurologists/psychiatrists toward demented patients were investigated by
      questionnaire. This figure represents a return rate of approximately 55% on the
      questionnaires. As is typical in Germany, no physicians were specializing in
      geriatric patients, and fewer general practitioners/internists than
      neurologists/psychiatrists had undergone supplementary psychogeriatric training.
      A higher percentage of the latter group estimated more than 10% of their elderly
      patients were demented. Both estimated Alzheimer's disease as less frequent than
      multi-infarct dementia. Physicians with training in psychogeriatrics claimed to
      treat more elderly patients than physicians without it. With regard to
      therapeutic procedure, physicians with psychogeriatric training prescribed
      nootropics more guardedly. The data from this pilot study suggest that there are
      no eminent discrepancies between the different medical groups with regard to
      psychogeriatric care, but there is a great need for supplementary training.

PMID- 7579016
TI  - Patients with dementia in group living: experiences 4 years after admission.
AB  - Sixteen patients with dementia were studied 4 years after admission to group
      living (GL) units, an intermediate level of dementia care. Of eight patients who
      were still alive, four lived in the GL units and four had been institutionalized.
      The eight patients who had died had spent 89% of their survival time in GL.
      Aggression was the most frequent cause of institutionalization.

PMID- 7579018
TI  - Dimensions of social support and social conflict as predictors of caregiver
      depression.
AB  - The goal of this research was to examine the relationship of family social
      support and social conflict to stressors and depression. Fifty-seven caregiving
      women were interviewed regarding caregiving stressors, social support, and social
      conflict. Three dimensions of social support and social conflict were assessed:
      instrumental, informational, and affective. The findings supported the importance
      of distinguishing between social support and social conflict, and among the three
      dimensions of support and conflict. Respondents reported higher levels of support
      than of conflict, but consistent with earlier research, social support was not
      related as strongly to outcomes as social conflict was. Although instrumental
      support was related significantly to depression, informational and emotional
      support was not. Social conflict, however, was significantly related to
      depression. Both emotional conflict and informational conflict were significant
      predictors of depression. Implications for future research and interventions are
      discussed.

PMID- 7579019
TI  - The international classification of impairments, disabilities, and handicaps: a
      mental health perspective.

PMID- 7579015
TI  - Economic analysis of Alzheimer's disease in outpatients: impact of symptom
      severity.
AB  - To assess the economic burden of Alzheimer's disease (AD), we carried out a cross
      sectional prevalence cost-of-illness study in France. Fifty-one probable AD
      patients (NINCDS-ADRDA) actually treated in ambulatory care were recruited in two
      university outpatient centers. Demographic, clinical (including actual Mini
      Mental State Examination scores), and economic data were collected by clinical
      investigators and trained interviewers. Total costs included actual expenditures
      such as direct medical costs and direct nonmedical costs, as well as indirect
      costs (loss of earnings due to loss of productivity). Cost valuation was based on
      the societal perspective using an opportunity costing approach. We found that
      indirect costs represented a significant portion of total costs (36%-40%). In
      terms of expenditures, patients and caregivers were found to bear the major part
      of AD total costs. We found a positive and significant correlation between
      disease severity and costs. Our findings support the hypothesis of a relationship
      between disease evolution and healthcare costs.

PMID- 7579017
TI  - Usefulness of the Clinical Dementia Rating scale in screening for dementia.
AB  - The Clinical Dementia Rating (CDR) scale is a qualitative staging instrument that
      has traditionally been used for assessing the severity of dementia. We used it
      for screening dementia in a population study of 75-, 80-, and 85-year-old people.
      The modified CDR scale was easy to establish and it proved to be useful in
      screening dementia. A more thorough examination is needed in the second phase to
      identify the false positives. The sensitivity of the CDR scale was 95% and the
      specificity 94%.

PMID- 7579020
TI  - Ecological measures of cognitive functioning: a validation study.
AB  - Observed cognitive decline in the elderly has been widely reported in the
      literature. The relation of experimental cognitive ability measures to real-world
      cognitive competence has been questioned. This research examines the validity of
      English-language versions of two measures of everyday competency: the Memory in
      Reality test involving object placement recall and the Coin Test, a money-sorting
      task. The measures were developed as part of a Swedish epidemiologic study.
      Validity was evaluated by comparison of these tasks with standard cognitive tests
      and with a measure of metamemory. It was expected that the ecological measures
      would have a stronger association with metamemory than the standard tests.
      Subjects were 93 community-dwelling women, aged 75 and older. The ecological
      tasks correlated positively with the standard tests, but there were inconsistent
      relations of both standard and ecological measures with metamemory. The results
      partly support use of these measures for evaluating everyday functioning.

PMID- 7579021
TI  - Effect of staff turnover and the social environment on depressive symptoms in
      nursing home residents.
AB  - Although one would expect a relationship on the basis of anecdotal evidence,
      there is little objective evidence for a hypothesized relationship between the
      social environment provided in institutional settings and the psychological well
      being of the residents. In an attempt to operationalize this hypothesis, the
      present study examined the effect of nursing staff turnover, frequency of
      visitors, and the presence or absence of close friends on depressive symptoms
      among nursing home residents. Once physical dependency and past history of
      depression were taken into account, there was no demonstrable relationship
      between staff turnover and depressive symptoms among the residents of this sample
      of nursing homes. There was, however, a significant relationship between absence
      of close friends among other residents and depressive symptoms, although only 13%
      of the total variance was explained.

PMID- 7579023
TI  - One year on tacrine (THA): clinical and biochemical effects in patients with
      dementia of the Alzheimer type.
AB  - Fourteen patients suffering from dementia of the Alzheimer type were treated with
      tacrine (tetrahydroaminoacridine, THA) for 1 year in an open trial. Clinical
      results were evaluated every third month with neuropsychological tests and rating
      scales. During the dose-finding, two patients were temporarily withdrawn from
      medication and one patient was excluded because of elevated levels of liver
      enzymes. With individualized doses the treatment caused few side effects. Plasma
      levels of THA varied substantially among patients and correlated with elevation
      of liver enzymes but not with clinical response. Two patients showed a gradual
      increase in plasma levels of THA despite unchanged doses. Although results of the
      neuropsychological tests and clinical ratings were mostly negative, the study
      indicates that THA can be administered safely for prolonged periods of time.
      Clinical observations and dose-titration strategy in relation to side effects are
      discussed.

PMID- 7579022
TI  - Age of onset and medical illness in older depressed inpatients.
AB  - Age of onset of depressive episodes may serve as a useful marker of pathogenetic
      heterogeneity in late-life depression. Medical illness may play an important role
      in the pathogenesis of depression in the elderly, but its relationship to age of
      onset has not been carefully examined. We prospectively studied 110 older
      inpatients with DSM-III-R major depression. Using multiple regression techniques,
      we found that medical illness was not independently associated with age of onset.
      Independent predictors of older age of onset were age, male sex, absence of
      substance abuse history, and absence of melancholia. Our discussion reconsiders
      the usefulness of age of onset as a primary research variable for elucidating
      heterogeneity in late-life depression.

PMID- 7579024
TI  - Vitamin B12 deficiency and dementia.
AB  - We set out to investigate the possible beneficial effects on cognitive function
      of demented patients with cobalamin deficiency after cobalamin replacement. A
      total of 181 consecutive, demented (DSM-III or DSM-III-R criteria and score below
      24 on the Mini-Mental State Examination [MMSE]) outpatients (mean age 77.5 years)
      were prospectively evaluated and had their vitamin B12 level measured by
      radioimmunoassay. The frequency of vitamin B12 deficiency (less than 200
      pg/mliter) was 25% (46 patients). Treatment outcome was obtained in 19 patients
      (19 of 46). Despite cobalamin replacement, 16 of 19 patients persisted in showing
      progressive decline during follow-up visits (3 to 24 months). The nonresponse to
      vitamin B12 replacement in most cases seems to reflect the presence of associated
      irreversible dementia or a follow-up of shorter duration in a few patients. All
      of the patients who showed some improvement (MMSE returned to normal values) had
      mild dementia with a history of less than 2 years. Thus, screening for B12
      deficiency should be considered in patients with recent onset of mild mental
      status changes.

PMID- 7579025
TI  - A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric
      patients with major depression. The Fluoxetine Collaborative Study Group.
AB  - Depression in the geriatric population is a frequent, serious, and potentially
      reversible disorder, yet relatively few blinded, controlled, antidepressant
      trials have been reported. A number of age related issues complicate safe and
      effective pharmacotherapy. In a 6-week, double-blind trial in moderately to
      severely depressed (nonpsychotic) outpatients over age 60, fluoxetine (N = 335)
      was statistically significantly more efficacious than placebo (N = 336) in
      overall response (43.9% vs. 31.6%, p = .002) and remission (31.6% vs. 18.6%, p <
      .001) rates. Analyses of early discontinuations because of an adverse drug event
      revealed no statistically significantly greater rate with fluoxetine (n = 39;
      11.6) than was seen with placebo (n = 29; 8.6%). These results corroborate that
      major depression in an older population is responsive to antidepressant
      pharmacotherapy. Specifically, fluoxetine, at a conventional 20-mg dose, was both
      safe and effective relative to placebo in this special population.

PMID- 7579026
TI  - Ability of a trained primary healthcare nurse to discriminate dementia from other
      psychogeriatric disorders.
AB  - The aim of this study was to evaluate the ability of a trained primary health
      care (PHC) nurse to discriminate dementia, by systematic assessments, from other
      psychogeriatric diseases. The reported study emanates from a dementia prevalence
      survey in an elderly (65+) population (n = 851). Forty-two frail elderly people
      (mean age 77.8 years) referred to a psychogeriatric hospital for further clinical
      investigation were tested. Dementia rating scales were used by the trained nurse,
      who noted her clinical observations systematically as well. The instrument
      results of the testing procedures, evaluated in combination with the clinical
      picture of the patients, were correlated to the DSM-III-R criteria of dementia.
      Thereafter, the nurse's judgements were compared with the clinical diagnoses
      based on thorough geropsychiatric investigations. The nurse's diagnoses of
      moderate and severe dementia had a sensitivity of 80% and a specificity of 82%.
      The predictive value of a positive test for moderate and severe dementia was 87%.
      When the mildly demented patients were included, sensitivity was 93%, specificity
      was 75%, positive predictive value was 90%, and kappa value was .70.

PMID- 7579028
TI  - Pharmacokinetics of amphotericin B in rats as a function of dose following
      constant-rate intravenous infusion.
AB  - Amphotericin B (AmB) is widely used for the treatment of systemic mycoses. The
      current therapeutic regimens for this drug are complex and somewhat empirical, in
      part because of very limited information about the disposition kinetics of this
      agent. In this study, we examined the disposition kinetics of AmB as a function
      of dose and estimated clearance values using a steady state study design in an
      animal model. Groups of male Sprague-Dawley rats were given different two-step
      infusion regimens to achieve three different steady state concentrations (i.e.,
      three different total infused doses). We observed no significant differences in
      systemic clearance among the three AmB doses studied. Similarly, only small
      differences were seen in volumes of distribution as a function of dose. However,
      renal clearance decreased significantly as the total infused dose was increased
      (0.76 +/- 0.33, 0.86 +/- 0.24, and 0.37 +/- 0.04 mL min-1 kg-1 for the low-medium
      and high-dose groups, respectively; p < 0.05). Signs of renal impairment were
      observed in the high-dose group, as documented by decreased creatinine clearance.
      Dose-dependent renal clearance may have been due either to nephrotoxicity
      associated with the high dose of AmB and/or to saturation of an active secretion
      process. Furthermore, clearance values estimated from steady state conditions
      were similar to those from time-averaged values (based on the estimation of area
      under the plasma concentration-time profile). This suggests that clearance
      calculations from time-averaged concentrations provide reasonable estimates,
      since steady state plasma concentrations could be reliably determined. However,
      the possibility that a true tissue steady state condition was not achieved with
      our study design cannot be ruled out. Further investigation is necessary to
      identify the renal excretion mechanisms of AmB and to reach steady state tissue
      concentration to confirm the estimation of systemic clearance.

PMID- 7579027
TI  - Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses,
      linearity and plasma protein binding.
AB  - The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be
      close to linear in a crossover study comparing administration of single 2, 3, 4,
      and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the
      capsules were bioequivalent to the proposed therapeutic tablet formulation (4
      mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine
      collected up to 72 h after each administration. Plasma levels indicated a rapid
      absorption (tmax approximately equal to 2 h) and an elimination half-life of
      about 13 h. Clearance and volume of distribution were modest (ratios to
      bioavailability: CL/F approximately equal to 29 mL min-1; Vz/F approximately
      equal to 32 L); urinary excretion was approximately 9% of dose, corresponding to
      a renal clearance of only 3 mL min-1 (a value consistent with the rate of
      glomerular filtration of unbound drug). In vitro, binding to plasma proteins,
      estimated from radioactivity levels following dialysis of 14C-labelled
      reboxetine, appeared to be dominated by alpha 1-acid glycoprotein without marked
      saturation up to plasma concentrations of over 500 ng mL-1 (2.8-3.1% unbound with
      human plasma from three additional volunteers; 1.8-2.0% for 2 gL-1 orosomucoid
      alpha 1-acid glycoprotein, and 46.4-47.4% for 40 g L-1 albumin), whilst the mean
      Cmax in the current study was much lower (164 ng mL-1 after a 5mg dose).

PMID- 7579030
TI  - The effect of caffeine on the pharmacokinetics of acetaminophen in man.
AB  - The influence of caffeine (60 mg) was studied on the pharmacokinetic
      characteristics of acetaminophen (500 mg single dose) in ten healthy male human
      volunteers in a complete cross-over design. A high-performance liquid
      chromatography (HPLC) method was used to analyse serum drug concentrations.
      Caffeine caused a highly significant (p < 0.01) increase in AUC and AUMC, a
      significant (p < 0.05) increase in Cmax, and a significant (p < 0.05) decrease in
      clearance (C1/F) of acetaminophen. We conclude that caffeine taken in doses
      commonly available commercially or in a cup of coffee can significantly
      potentiate the therapeutic potential of acetaminophen in man.

PMID- 7579029
TI  - Selective adherence of a sucralfate-tetracycline complex to gastric ulcers:
      implications for the treatment of Helicobacter pylori.
AB  - The adherence of a sucralfate-tetracycline complex to gastric ulcers and to
      nearby non-ulcer sites was determined in the rabbit antrum. Persistent gastric
      ulcers were produced by a previously described method. The presence of the
      complex was assessed 1 and 4 h after dosing. Drug adherence was determined by
      quantitation of aluminum in stomach wall biopsies. Significantly more aluminum
      adhered to ulcer sites than to nearby non-ulcer sites. Adherence of the complex
      did not significantly decrease from 1 to 4 h. The complexation of tetracycline to
      sucralfate did not alter the selective adherence of sucralfate to gastric ulcers,
      providing a mechanism of ulcer site-selective drug delivery in the treatment of
      Helicobacter pylori gastric ulcer disease.

PMID- 7579031
TI  - Pharmacokinetics and antitumour activity of a new anthracycline, DA-125, after
      intravenous administration to subcutaneously implanted Lewis-lung-carcinoma
      bearing mice.
AB  - The pharmacokinetics and tissue distribution of M1-M4 were compared after
      intravenous (i.v.) administration of DA-125, 25 mg kg-1, to BDF1 mice (n = 5 at
      each sampling time) and subcutaneously implanted Lewis-lung-carcinoma-bearing
      BDF1 mice (n = 10 at each sampling time. The mean plasma concentrations of M1-M4
      were not significantly different between the two groups of mice, and hence
      similar pharmacokinetic parameters for M1-M4 were obtained. The amount of M1 in
      the lung was significantly greater in the tumour-bearing mice than in the control
      mice, resulting in a greater AUAt in the tumour-bearing mice (18,600 against 8940
      micrograms min g-1), and vice versa in the liver (962 against 3840 micrograms min
      g-1). However, the corresponding values for other tissues were comparable between
      the control and tumour-bearing mice. The amount of M1 was greatest in the lung
      for up to 2 h in the tumour-bearing mice. M2 was the predominant metabolite among
      M1-M4 excreted in 24 h urine by both groups of mice; 8.36 and 10.7% of the i.v.
      dose were excreted in 24 h urine as M2--expressed in terms of DA-125--by the
      control and tumour-bearing mice, respectively. The amount of M1 in the tumour
      mass reached a mean Cmax of 3.75 micrograms g-1 immediately after i.v.
      administration of DA-125 to the tumour-bearing mice, then declined very slowly to
      an amount that remained almost constant for up to 24 h. This suggested that M1
      has high affinity for the subcutaneously implanted Lewis lung carcinoma. The
      antitumour activity, such as the increase in life span (ILS) and tumour growth
      inhibition (TGI) of DA-125, 6-48 mg kg-1, and adriamycin (ADM), 3-18 mg kg-1,
      were also compared in subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1
      mice after four weekly i.v. administration of the drugs on days 1,8,15, and 22
      following tumour implantation. More than three out of six mice survived as tumour
      free for longer than 70 d at a DA-125 dose range of 6-24 mg kg-1, but there were
      no tumour-free mice at any dose of ADM. Assuming ILS values higher than 30% to be
      effective, DA-125 doses ranging from 6 to 24 mg kg-1 were effective in increasing
      the life span, which ADM does only within the dose range of 6-12 mg kg-1.

PMID- 7579032
TI  - Pharmacokinetics of epidurally administered nicomorphine with its metabolites and
      glucuronide conjugates in patients undergoing pulmonary surgery during combined
      epidural local anaesthetic block and general anaesthesia.
AB  - After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nicomorphine)
      in 10 patients undergoing pulmonary surgery, the parent compound was quickly
      metabolized into the metabolites 6-mononicotinoylmorphine and morphine. The mean
      apparent half-lives (+/- SD) of elimination were 10 min (0.165 h +/- 0.053 h) for
      3,6-dinicotinoylmorphine and 1.77 h +/- 1.23 h for 6-mononicotinoylmorphine.
      Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6
      glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and
      morphine-6-glucuronide are similar: 3.63 h +/- 1.63 h, 4.10 h +/- 0.57 h, and
      4.20 h +/- 1.64 h respectively. The possible glucuronide conjugate of 6
      mononicotinoylmorphine was not detected. The prodrug 3,6-dinicotinoylmorphine was
      biotransformed into three active compounds: 6-mononicotinoylmorphine, morphine,
      and morphine-6-glucuronide.

PMID- 7579033
TI  - Measurement of free concentration of SDZ ICM 567 in blood and muscle using
      microdialysis sampling.

PMID- 7579036
TI  - Nobel Lecture. G proteins and regulation of adenylyl cyclase.

PMID- 7579034
TI  - Comments concerning 'The penetration of amphotericin B from an Intralipid
      formulation into fibrin loci in a rabbit model of candidiasis'.

PMID- 7579037
TI  - Carrier-mediated lactate entry into isolated hepatocytes from fed and starved
      rats: zonal distribution and temperature dependence.
AB  - We examined the possibility of quantitative differences in lactate entry into
      periportal and perivenous hepatocytes under different nutritional states. The
      rate of 14C-L(+)-lactate uptake was determined after 15-second incubations with
      freshly isolated zonally separated hepatocytes using a centrifuge stop technique
      at 37 degrees C and 4 degrees C, in the presence or absence of either differing
      amounts of unlabelled lactate or of a hepatocyte lactate transport inhibitor,
      alpha-cyano-3-hydroxycinnamate. Total entry as well as carrier mediated entry of
      14C-L(+)-lactate into the isolated cell populations was found to be similar in
      periportal and perivenous hepatocytes, irrespective of the nutritional state of
      the animal. Periportal and perivenous hepatocytes showed a greater tendency to
      transport lactate when isolated from starved animals, in agreement with
      previously reported data from non-zonally separated isolated hepatocytes. The
      activity of the hepatocyte plasma-membrane lactate transporter was diminished
      between fourfold and eightfold in transport studies conducted at 4 degrees C;
      similar results were obtained in unseparated and zonally separated suspensions.
      Temperature dependence of the hepatocyte transporter is markedly less than that
      reported for the erythrocyte transporter.

PMID- 7579038
TI  - Nobel Lecture. Signal transduction: evolution of an idea.

PMID- 7579035
TI  - Amino acid composition of rat and human liver microsomes in normal and
      pathological conditions.
AB  - The amino acid composition of proteins from liver microsomes has been studied in
      rats and in human subjects with normal liver, with obstructive jaundice or liver
      cirrhosis. The pattern of the amino acid composition of microsomes appeared to be
      species-specific. Phenylalanine, threonine, serine, proline, histidine and
      [aspartic acid plus asparagine] were increased, while alanine, tyrosine, glycine
      and arginine were decreased in the human compared to the rat microsomes. In
      patients with obstructive jaundice of short duration (less than two months) only
      a slight decrease in leucine and phenylalanine could be noticed, while in the
      case of liver cirrhosis amino acid composition was markedly changed.

PMID- 7579039
TI  - Direct effects of vitamin D3 analogues on G-protein mediated signalling systems
      in rat osteosarcoma cells and rat pituitary adenoma cells.
AB  - In normal rats treated with 1,25(OH)2D3 or 24,25(OH)2D3, serum Ca2+, ALP, PRL and
      GH are significantly altered. In order to study the primary effect of vitamin D3
      analogues on target organ function, rat UMR 106 osteosarcoma and GH3 pituitary
      adenoma cells in monolayer culture were exposed accordingly. Surprisingly,
      prolonged exposure of these cell lines to physiological levels of either
      1,25(OH)2D3 or 24,25(OH)2D3 did not significantly affect the secretory parameters
      (ALP, PRL or GH) tested. However, 1,25(OH)2D3 exposure significantly reduced PTH-
      and Gpp(NH)p-elicited AC as well as Gpp(NH)p-stimulated PLC activities in the UMR
      106 cells. These changes were accompanied by an increase and decrease in the
      membrane contents of the G-protein subunits G36 beta and Gq/11 alpha,
      respectively. In contrast, 24,25(OH)2D3 remained without significant biological
      effect on these signalling systems despite concomitantly augmented levels of G36
      beta. TRH- and Gpp(NH)p-elicited PLC activities in the GH3 cells were
      significantly reduced by 1,25(OH)2D3 with a concurrent reduction in cellular
      amounts of Gq/11 alpha, however, 24,25(OH)2D3 did not significantly alter any
      signalling systems nor G-proteins analyzed. It is concluded that the osteoblastic
      and pituitary cell secretion of ALP, PRL and GH remain unaffected by the presence
      of 1,25(OH)2D3 and 24,25(OH)2D3, despite distinct alterations in components of G
      protein mediated signalling pathways. Hence, other factors like ambient Ca2+ may
      be responsible for the perturbed secretory patterns of ALP and PRL seen in
      vitamin D3 treated rats.

PMID- 7579040
TI  - Mechanism of liposome destabilization by polycationic amino acids.
AB  - Polycationic amino acids induce the leakage and fusion of liposomes containing
      anionic lipids. We have investigated the nature and extent of the changes in
      membrane physical properties caused by these polypeptides which could result in
      the observed membrane destabilization. We found that in the range of pH 5 to pH 7
      both poly-L-histidine and poly-L-lysine were ineffective in shifting the bilayer
      to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine,
      either in the presence of absence of 1-palmitoyl-2-oleoylphosphatidylserine. We
      also studied the gel to liquid crystalline phase transition properties of 1:1
      mixtures of phosphatidylserine and phosphatidylethanolamine, both in dimyristoyl
      forms as well as the 1-palmitoyl-2-oleoyl forms, as a function of pH and in the
      presence and absence of polycationic amino acids. We observed that these two
      lipids were largely miscible at all pH values and in the presence and absence of
      the polypeptides. However, there was some increased tendency for phase separation
      at higher pH and in the absence of polypeptide. Thus neither changes in curvature
      strain nor lateral phase separation induced by the polycationic amino acids could
      account for their marked ability to induce leakage and fusion.
      Phosphatidylethanolamine labelled with pyrene on one of the acyl chains gives
      rise to fluorescent emission from both monomer and excimer forms. The ratio of
      emission intensity from these two forms is indicative of lateral phase separation
      and the degree of lateral mobility of this probe. In equimolar mixtures of the 1
      palmitoyl-2-oleoyl forms of phosphatidylserine and phosphatidylethanolamine in
      the liquid crystalline phase at 30 degrees C we find little effect of pH on the
      ratio of excimer to monomer emission intensity. However poly-L-lysine markedly
      lowers the fraction of excimer emission from these liposomes through the pH range
      from 5 to 7. Poly-L-histidine lowers the excimer to monomer emission ratio at pH
      5 but not at pH 7. This is opposite to what one would expect for lateral phase
      separation and is interpreted at being the consequence of the polypeptide
      lowering the rate of lateral diffusion of the lipids. This effect of poly-L
      histidine is observed over a range of temperatures from 0 to 40 degrees C in both
      gel and liquid crystalline phases. There is no evidence from the behaviour of the
      pyrene fluorescent probe for lipid interdigitation.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7579041
TI  - Characterisation of protein structure/function relationship by sequence analysis
      without previous alignment: distinction between sub-groups of protein kinases.
AB  - Using an approach for protein comparison by computer analysis based on signal
      treatment methods without previous alignment of the sequence, we have analysed
      the structure/function relationship of related proteins. The aim was to
      demonstrate that from a few members of related proteins, specific parameters can
      be obtained and used for the characterisation of newly sequenced proteins
      obtained by molecular biology techniques. The analysis was performed on protein
      kinases, which comprise the largest known family of proteins, and therefore
      allows valid estimations to be made. We show that using only a dozen defined
      proteins, the specific parameters extracted from their sequences classified the
      protein kinase family into two sub-groups: the protein serine/threonine kinases
      (PSKs) and the protein tyrosine kinases (PTKs). The analysis, largely involving
      computation, appears applicable to large scale data-bank analysis and prediction
      of protein functions.

PMID- 7579042
TI  - Special issue in honor of Homer William Smith, D.Sc., on the occasion of the
      100th anniversary of his birth.

PMID- 7579043
TI  - Homer William Smith: a remembrance.

PMID- 7579044
TI  - Homer Smith: his contribution to physiology.

PMID- 7579045
TI  - Homer Smith: his contribution to the practice of nephrology.

PMID- 7579046
TI  - Homer Smith Award recipient--Peter Aronson.

PMID- 7579047
TI  - 1994 Homer W. Smith Award. From flies to physiology--accidental findings along
      the trail of renal NaCl transport.

PMID- 7579048
TI  - Isolated renal mucormycosis: case report and review.
AB  - The 15th reported case of isolated renal mucormycosis (infection of the kidney
      with fungus of the order Mucorales, in the absence of infection elsewhere in the
      body) is presented. The patient was a 36-year-old human immunodeficiency virus
      infected man, actively using iv drugs, who suffered 6 wk of flank pain and fever
      before diagnosis was made by percutaneous renal biopsy. He received 4 months of
      amphotericin B treatment, then no therapy for 6 months before dying with no
      evidence of mucormycosis. Isolated renal mucormycosis should be suspected in
      those with an underlying immunocompromising illness or history of iv drug use who
      have persistent flank pain and fever, but sterile urine cultures. Computed
      tomographic scanning with contrast should then be performed; findings of severe
      inflammation or bacterial infection, despite an indolent clinical course with
      sterile or nondiagnostic urine and blood cultures, are suggestive of isolated
      renal mucormycosis, and renal biopsy under computed tomographic guidance should
      be performed, despite the potential risk of disseminated infection. Although our
      patient was treated with amphotericin B alone, nephrectomy with or without
      amphotericin B therapy appears to be more likely to cure infection and relieve
      pain and constitutional symptoms.

PMID- 7579049
TI  - Exercise-induced acute renal failure associated with ibuprofen,
      hydrochlorothiazide, and triamterene.
AB  - Nonsteroidal anti-inflammatory drugs predispose to acute renal failure in
      conditions associated with decreased RBF. Such conditions include advanced age,
      hypertension, chronic renal insufficiency, diuretic use, and any condition
      decreasing effective circulating volume. Strenuous exercise also causes marked
      reductions in RBF. The patient discussed developed severe acute renal failure
      after strenuous exercise and therapeutic doses of ibuprofen and
      hydrochlorothiazide-triamterene. Urinalysis showed a nephritic sediment with red
      blood cell casts. Renal biopsy showed acute tubular necrosis and arteriolar
      nephrosclerosis. Although exercise-associated acute renal failure is uncommon,
      susceptible patients with exercise-induced renal ischemia and prostaglandin
      inhibition may develop this complication.

PMID- 7579050
TI  - The prognostic importance of left ventricular geometry in uremic cardiomyopathy.
AB  - The objective of this study was to determine the effect of left ventricular (LV)
      mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients.
      The Design was a multicenter, prospective inception cohort study with a median
      follow-up of 41 months. The Setting was three university-affiliated nephrology
      units. A total of 433 patients who (1) survived > 6 months from the start of ESRD
      therapy and (2) had a technically satisfactory baseline echocardiogram were
      studied. Measurements included a baseline clinical, laboratory and
      echocardiographic assessment. LV hypertrophy was present in 74% and LV dilation
      was present in 36% of patients. In patients with normal cavity volume (< or = 90
      mL/m2) and normal systolic function, high LV mass index (> 120 g/m2) and mass-to
      volume ratios (> 2.2 g/mL) were independently associated with late mortality (> 2
      yr after starting dialysis therapy). After adjusting for baseline age, diabetes,
      and ischemic heart disease, the relative risk for the former was 3.29 and for the
      latter was 2.24. Cavity volume was of no prognostic significance in this group.
      In patients with LV dilation and normal systolic function, high cavity volume (>
      120 mL/m2) and low mass-to-volume ratio (< 1.8 mL/m2) were independently
      associated with late mortality, the relative risk in the former being 17.14 and
      the latter being 4.27. LV mass index was of no prognostic significance in this
      group. The baseline echocardiographic classification, based on LV mass and cavity
      volume, was the strongest predictor of late mortality, after adjusting for age,
      gender, diabetes mellitus, coronary artery disease, angina pectoris, chronic
      hypertension, and hemoglobin and serum albumin levels.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579051
TI  - Cardiovascular abnormalities in children with autosomal dominant polycystic
      kidney disease.
AB  - It is known that adults with autosomal dominant polycystic kidney disease (ADPKD)
      have an increased incidence of cardiovascular abnormalities, including mitral
      valve prolapse. The cardiac manifestations of ADPKD in the pediatric population
      have not been well established. To determine the cardiac manifestations of
      children with ADPKD, echocardiography was performed in 154 children of 66
      families in which one parent has ADPKD. Eighty-six affected children and 68
      unaffected children were evaluated in a prospective, single-blinded manner by
      echocardiography. Affected children were defined as those with any cysts on a
      concurrent renal ultrasound or those predicted to be gene carriers by gene
      linkage analysis. A 12% incidence of mitral valve prolapse was found in the
      affected children compared with only 3% of the unaffected children (P < 0.05).
      ADPKD children, but not their unaffected siblings, demonstrate a significant
      correlation between left ventricular mass index and systolic blood pressure.
      Moreover, hypertensive ADPKD children have significantly larger left ventricular
      mass index than do normotensive ADPKD children. A 3.5% incidence of congenital
      heart disease was found in the affected group, whereas 2.9% of the unaffected
      children had congenital heart disease. It was concluded that systemic
      manifestations of ADPKD, particularly cardiovascular abnormalities, are present
      even in childhood and these warrant the clinician's attention.

PMID- 7579052
TI  - Dietary protein restriction, blood pressure control, and the progression of
      polycystic kidney disease. Modification of Diet in Renal Disease Study Group.
AB  - In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of
      200 study participants with autosomal dominant polycystic kidney disease (ADPKD)
      was conducted to determine the effect of lowering protein intake and blood
      pressure on the rate of decline in GFR. The rate of decline was faster in
      participants with ADPKD than in persons with other diagnoses, reflecting, in
      part, faster disease progression in the ADPKD group. Baseline characteristics
      that predicted a faster rate of decline in GFR in persons with ADPKD were greater
      serum creatinine (independent of GFR), greater urinary protein excretion, higher
      mean arterial pressure (MAP), and younger age. In patients with initial GFR
      values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein
      diet group nor assignment to a low blood pressure group significantly reduced the
      rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was
      not related to achieved protein intake or MAP. In participants with GFR values
      between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a
      somewhat more rapid decline in GFR. However, the more rapid decline in GFR did
      not appear to be due to a detrimental effect of low blood pressure or the
      antihypertensive agents used to reach the low blood pressure goal. Lower protein
      intake, but not prescription of the keto acid-amino acid supplement, was
      marginally associated with a slower progression of renal disease.

PMID- 7579053
TI  - Causes of death in autosomal dominant polycystic kidney disease.
AB  - To determine the causes of death in autosomal dominant polycystic kidney disease
      (ADPKD) patients and to examine whether the extrarenal manifestations of ADPKD
      influence the causes of death, the medical records of 129 patients who died
      between 1956 and 1993 were reviewed; 58% of the 129 patients had an autopsy
      performed. Seventy-seven percent died after reaching ESRD. The mean age at death
      increased from 51 yr for those who died before 1975 to 59 yr for those who died
      after 1975, reflecting the introduction of renal replacement therapies. The most
      common cause of death before 1975 was infection (30%), followed by uremia (28%)
      and cardiac disease (21%); after 1975, these were cardiac disease (36%) and
      infection (24%). Infection was equally prevalent before and after 1975,
      presenting as sepsis in 94% and directly relating to ADPKD in 47% of these
      patients. Underlying factors for cardiac death were cardiac hypertrophy, seen in
      89% of all autopsied patients, and coronary artery disease, seen in 81%. A
      neurologic event was the cause of death in 12% of patients; these were ruptured
      intracranial aneurysm in 6%, hypertensive intracranial hemorrhage in 5%, and
      ischemic stroke in 1%. The mean age of those who died of ruptured intracranial
      aneurysm was 37 yr. No patient died of renal cancer. Liver cysts were the most
      common extrarenal manifestation, seen in 70% of the autopsied cases; cysts in
      other organs were very rare. Colonic diverticula were found in 21%. Thus, the
      renal and extrarenal manifestations of ADPKD are important contributors to
      morbidity and mortality.

PMID- 7579054
TI  - Effect of atrial natriuretic peptide on renal and vascular permeability in
      diabetes mellitus.
AB  - Synthetic human atrial natriuretic peptide (ANP) (102-126) 0.01 microgram/kg per
      minute or vehicle was intravenously infused for 2 h in 10 patients with insulin
      dependent diabetes mellitus and microalbuminuria (albumin excretion, 20 to 200
      micrograms/min) and in 10 healthy subjects. In the diabetic group, the
      immunoglobulin G clearance was higher, but both size index and charge index as
      calculated from albumin and immunoglobulin clearances were equal compared with
      normal values. The fractional clearances of small dextrans (< 3.6 nm) were lower
      in diabetics, which was compatible with a depressed hydraulic permeability (Kf).
      During ANP infusion, the excretion of albumin and immunoglobulin G increased in
      the diabetic subjects (189 +/- 12 to 521 +/- 84 and 7.1 +/- 3.5 to 21 +/- 8.1
      micrograms/min, respectively; both P < 0.05) only. In the diabetics, the
      clearance of dextrans > 54 A increased and our calculations indicated an increase
      in "shut-flow" (omega o). The transcapillary escape rate of albumin, which was
      elevated in the diabetics at baseline, increased in the diabetic group only.
      Thus, ANP uncovers altered size selectivity of the filtration barrier in a phase
      that is otherwise characterized by charge-selective changes only. Moreover, the
      increased susceptibility of the glomerular capillaries in diabetics to ANP seems
      to be part of a more generalized capillary abnormality, because ANP also
      increases the transcapillary escape of albumin.

PMID- 7579055
TI  - Expression and preferential inhibition of inducible nitric oxide synthase in
      aortas of endotoxemic rats.
AB  - Septic shock is associated with high mortality. There is in vitro evidence that
      the induction of nitric oxide synthase (iNOS) in vascular smooth muscle cells may
      be an important mediator of the systemic vasodilation and hypotension associated
      with sepsis. In this study, an in vivo murine model of sepsis was used to further
      examine this important question. Lipopolysaccharide (LPS), the major wall
      component of gram-negative bacteria, was administered to rats. By the use of a
      selective cDNA probe for iNOS, mRNA for iNOS was demonstrated in the aortas of
      these rats. The functional significance of this iNOS was then examined with
      aminoguanidine, a preferential inhibitor of iNOS. Aminoguanidine reversed the
      blunted phenylephrine-evoked contraction of endothelium-denuded aortic rings from
      LPS-treated rats or rings exposed to LPS in vitro. Aminoguanidine did not impair
      the relaxation of aortic rings with endothelium to acetylcholine, a known
      stimulator of endothelial NOS. The reversal of LPS-induced vascular
      hyporesponsiveness by aminoguanidine therefore strongly supports the functional
      importance of iNOS mRNA expression in the aorta of endotoxemic rats. Future
      clinical trials in treating septic shock should therefore consider the
      preferential inhibition of iNOS while maintaining the integrity of endothelial
      NOS.

PMID- 7579057
TI  - Cardiopulmonary baroreflex function in nephrotic rats.
AB  - Efferent renal sympathetic nerve activity is increased in experimental nephrotic
      syndrome and exhibits attenuated cardiopulmonary baroreflex inhibition during
      volume expansion in anesthetized rats. Additional studies were performed in
      conscious rats to avoid the potentially confounding influences of anesthesia;
      these studies used another more specific standardized stimulus for
      cardiopulmonary baroreflex activation. Sprague Dawley rats were studied 3 to 4 wk
      after adriamycin injection (3.5 mg/kg iv); all rats developed proteinuria. In
      sinoaortic denervated rats (anesthetized), graded frequency stimulation of the
      central end of the cut right vagus nerve produced frequency-dependent decreases
      in mean arterial pressure, heart rate, and efferent renal sympathetic nerve
      activity. The decreases in mean arterial pressure and heart rate were similar in
      control and nephrotic rats, but efferent renal sympathetic nerve activity
      decreased significantly less in nephrotic than control rats over the entire
      frequency range (P < 0.02). In sinoaortic denervated rats (conscious), 10% body
      weight isotonic saline volume expansion decreased mean arterial pressure, heart
      rate, and efferent renal sympathetic nerve activity. The decreases in mean
      arterial pressure and heart rate were similar in control and nephrotic rats, but
      efferent renal sympathetic nerve activity decreased significantly less in
      nephrotic than control rats over the entire period of volume expansion (P <
      0.04). In nephrotic syndrome, the cardiopulmonary baroreflex inhibition of
      efferent renal sympathetic nerve activity is decreased; the defect lies in the
      central portion of the reflex. This may contribute to the observed increase in
      efferent renal sympathetic nerve activity in nephrotic syndrome.

PMID- 7579056
TI  - The effects of cyclosporine and prednisone on serum lipid and (apo)lipoprotein
      levels in renal transplant recipients.
AB  - Disturbances of lipid metabolism are frequently encountered after renal
      transplantation and have been ascribed to the use of cyclosporine (CsA) and
      corticosteroids, but the individual contribution of each of these drugs remains
      uncertain. The individual effects of CsA and prednisone (Pred) on serum lipid and
      (apo)lipoprotein levels were compared in a prospective randomized trial. All
      patients received CsA and Pred during the first 3 months after transplantation.
      Subsequently, they were allocated to either withdrawal of Pred or conversion from
      CsA to azathioprine (Aza). Serum lipids and (apo)lipoproteins, including
      lipoprotein(a) (Lp(a)), were measured at regular intervals during the first year
      after renal transplantation. Analysis of variance for repeated measures of the
      first year results showed higher values for serum triglycerides (P < 0.001) and
      lower high-density lipoprotein (HDL) cholesterol levels (P < 0.05) in the CsA
      monotherapy group (N = 59) as compared with the AzaPred group (N = 63). At 1 yr
      after transplantation, CsA-treated patients had significantly higher Lp(a) levels
      (CsA: median, 105 (interquartile range 42 to 340) mg/L; Aza-Pred: 46 (25 to 176)
      mg/L; P < 0.05). The withdrawal of Pred in the CsA group resulted in a large fall
      in HDL cholesterol (27 +/- 30% at 5 months after transplantation) and an increase
      in triglycerides (49 +/- 73% at 6 months). A reversion of these changes was
      observed in patients who were retreated with Pred. Multiple linear regression
      analysis showed an independent correlation between the use of Pred and HDL
      cholesterol level, whereas the use of CsA was independently associated with the
      concentration of Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579058
TI  - Fibronectin mRNA in the developing glomerular crescent in rabbit antiglomerular
      basement membrane disease.
AB  - Fibronectin is a multifunctional matrix protein important in wound healing that
      is markedly increased in glomerular crescents. A previous report established two
      phases of fibronectin metabolism in crescent formation in an anti-glomerular
      basement membrane model of crescentic nephritis in the rabbit. Phase I was
      associated with increased glomerular fibronectin content from plasma. Phase II
      was associated with increased fibronectin mRNA in glomeruli. To examine the
      hypothesis that fibronectin is synthesized in the developing crescent, rabbit
      fibronectin cDNA was cloned, sense and antisense riboprobes were prepared and
      their specificity under the conditions to be used was validated and in situ
      hybridization studies were performed in the model. The results showed that the
      cells in the developing glomerular crescent express an intense fibronectin mRNA
      signal at Day 7 and that this signal persisted in cells of the crescent at Day
      14. This result shows that fibronectin synthesis does indeed take place in cells
      of the developing crescent in this model and supports the hypothesis that
      fibronectin may be an important agent regulating crescent formation and fibrosis.

PMID- 7579060
TI  - Translumbar inferior vena cava catheter for long-term hemodialysis.
AB  - Vascular access failure is a major cause of morbidity and even mortality in
      patients on chronic hemodialysis. The failure of conventional vascular access and
      thrombosis of the superior vena cava in a patient with ESRD was successfully
      treated by the percutaneous insertion of a hemodialysis catheter directly into
      the inferior vena cava. The translumbar access to the inferior vena cava has been
      used successfully in bone marrow transplant recipients and may also be used as a
      last choice for long-term hemodialysis when conventional access is difficult.

PMID- 7579059
TI  - Regulation of macrophage growth responses to colony-stimulating factor-1 by 1,25
      dihydroxyvitamin D3.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has previously been shown to affect the
      biology of a variety of immune cells, including the functions of macrophages. The
      effect of the vitamin D metabolite on the proliferative responses of macrophages
      to the cytokine colony-stimulating factor-1 (CSF-1) has been studied. It was
      found that this substance was able to suppress the growth responses of
      macrophages to CSF-1 as assessed by macrophage-tritiated thymidine uptake and
      also by cell counts. The effect was specific to this vitamin D metabolite because
      another vitamin D analogue, 25 hydroxyvitamin D3, did not have a similar effect
      on the responses of such cells to CSF-1. The results yield information on the
      regulatory role of 1,25(OH)2D3 on macrophage growth. It would appear that this
      vitamin D metabolite may act as a negative autoregulatory cytokine because it is
      produced by the macrophage when it is activated. A schema can be envisaged where
      CSF-1 is delivered to the macrophage to activate it and to cause it to
      proliferate. In the process, it also secretes 1,25(OH)2D3, which exerts a
      suppressive action to dampen this response.

PMID- 7579061
TI  - The evaluation of renal transplant candidates: clinical practice guidelines.
      Patient Care and Education Committee of the American Society of Transplant
      Physicians.

PMID- 7579062
TI  - Elevated superoxide generation in mononuclear phagocytes by treatment with 1
      alpha hydroxyvitamin D3: changes in kinetics and in oxidase cytosolic factor p47.
AB  - The effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) treatment on the
      superoxide production of phagocytic cells in patients undergoing continuous
      ambulatory peritoneal dialysis (CAPD) was studied. A 3-day treatment of CAPD
      patients with 3 micrograms per day of 1 alpha OHD3 (high-dose treatment)
      significantly increased NADPH oxidase and killing activities in peritoneal
      macrophages and peripheral blood monocytes (P < 0.001) as compared with low-dose
      (0.25 microgram/day of 1 alpha OHD3) treatment or nontreatment. The high oxidase
      activity observed in macrophages and monocytes after the treatment with 1 alpha
      OHD3, correlated significantly to the increase in the amount of the cytosolic
      factor p47 of the NADPH oxidase as detected by western blotting analysis.
      Superoxide production by the peripheral blood neutrophils of these patients only
      slightly increased with 1 alpha OHD3 treatment, and the amount of p47 was not
      affected by 1 alpha OHD3 administration. In order to evaluate the significance of
      the oxidase cytosolic factor in dictating oxidase activity, a reconstitution of
      NADPH oxidase was conducted by mixing macrophage cytosols and membranes in a cell
      free system. The addition of macrophage cytosol from patients on high-dose
      treatment to macrophage membranes from patients in all of the categories of
      treatment resulted in significantly higher (P < 0.001) superoxide production as
      opposed to the macrophage cytosol from nontreated patients. These results suggest
      that 1,25(OH)2D3 causes an increase in NADPH oxidase activity in the peritoneal
      macrophages and monocytes of CAPD patients by inducing synthesis and elevating
      the amount of the cytosolic factor p47.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579064
TI  - Hyperhomocysteinemia and the risk for vascular disease in hemodialysis patients.
AB  - The objective of this study was to examine if hyperhomocysteinemia is associated
      with occlusive vascular disease in hemodialysis patients. The study design
      included risk factor analysis and determination of serum homocysteine in
      hemodialysis patients. Fifty chronic uremic patients on regular hemodialysis
      treatment were studied. Twenty-four patients had coronary, cerebral, or
      peripheral signs of occlusive vascular disease. Cerebral vascular disease was
      diagnosed by computed tomography, arterial angiography, or Doppler sonography of
      the carotid and vertebral arteries. Coronary vascular disease was diagnosed by
      documented history of myocardial infarction or by coronary angiography. The
      diagnosis of peripheral vascular disease was established by angiography of the
      lower limb arteries. In all control patients, Doppler sonography of the carotid,
      vertebral, and lower limb arteries and thallium-201 exercise imaging were without
      pathologic results. Measurements included blood pressure, body mass index,
      smoking behavior, serum homocysteine (measured by gas chromatography/mass
      spectrometry), serum total, low-density lipoprotein, and high-density lipoprotein
      cholesterol, lipoprotein (a), triglycerides, and plasma fibrinogen. In a stepwise
      multiple logistic regression analysis, high serum homocysteine was significantly
      associated with occlusive arterial disease (R = 0.23; P = 0.031). Furthermore,
      hypertension (R = 0.18; P = 0.058), but not serum total, low-density lipoprotein,
      and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides,
      diabetes mellitus, body mass index, plasma fibrinogen, and smoking behavior, was
      significantly associated with atherosclerosis. Our results support the hypothesis
      that hyperhomocysteinemia is an independent risk factor for vascular disease in
      hemodialysis patients.

PMID- 7579063
TI  - Multicenter study of lipoprotein(a) and apolipoprotein(a) phenotypes in patients
      with end-stage renal disease treated by hemodialysis or continuous ambulatory
      peritoneal dialysis.
AB  - Numerous studies have investigated lipoprotein(a) (Lp(a)) plasma concentrations
      in patients with ESRD, a patient group with an enormous risk for atherosclerosis.
      The reported differences in Lp(a) between controls and patients vary from a
      decrease of 49% to an increase of more than 1,000%. However, data are not
      consistent, mostly because of problems with statistical analysis, and only
      limited data are available for patients treated by continuous ambulatory
      peritoneal dialysis (CAPD). To estimate the significance of Lp(a) in ESRD and to
      demonstrate the statistical pitfalls concerning Lp(a) in case-control studies, a
      large multicenter study including 702 patients treated by either hemodialysis
      (HD) (N = 534) or CAPD (N = 168) was conducted, and results were compared with
      results from 256 healthy controls. Both patient groups showed significantly
      elevated Lp(a) levels in comparison with controls: 23.4 +/- 25.0 mg/dL (P <
      0.005; HD) and 34.6 +/- 38.4 mg/dL (P < 0.0001; CAPD) versus 18.4 +/- 22.8 mg/dL
      (controls). CAPD patients showed significantly higher Lp(a) values than did
      patients treated by HD (P < 0.001). The difference between the two treatment
      groups possibly reflects an overproduction of Lp(a) to compensate for protein
      losses in CAPD patients. Both treatment groups included significantly more
      patients with Lp(a) values greater than the 75th percentile (25.6 mg/dL) of the
      control group (33.9 and 41.7% for HD and CAPD, respectively; P < 0.005). The
      higher Lp(a) values in patients were not explained by differences in isoform
      frequencies and the increase in Lp(a) was apolipoprotein(a) type specific: only
      patients with high-molecular-weight apolipoprotein(a) isoforms showed a
      significant elevation in Lp(a) levels. The increased plasma concentrations of
      Lp(a) may contribute to the high risk for atherosclerosis in ESRD, especially in
      patients treated by CAPD. Finally, it is believed that small sample sizes are
      responsible for the diverging results in Lp(a) literature.

PMID- 7579065
TI  - The relationship between calcium, phosphorus, and sodium intake, race, and blood
      pressure in children with renal insufficiency: a report of the Growth Failure in
      Children with Renal Diseases (GFRD) Study.
AB  - Nutritional data compiled during the Growth Failure in Children with Renal
      Diseases Clinical Trial were analyzed to determine the relationship between the
      dietary intake of divalent minerals and sodium, nutritional status, and serum
      calcium, phosphorus, and parathyroid hormone (PTH) concentrations and blood
      pressure in black versus white children. One hundred eighteen patients are
      included in this report; 25 were black (21%) and 93 were white (79%). Although
      more of the blacks were male, the age distribution, midarm circumference, midarm
      muscle circumference, blood pressure, and serum calcium, phosphorus, and PTH
      concentrations were comparable in the two groups. Phosphorus intake was within
      the recommended daily allowance in both groups; in contrast, calcium intake was
      inadequate in all patients: 81% of the recommended daily allowance in whites, and
      74% in blacks. Sixteen children were noted to be hypertensive during the
      observation period; six patients were receiving a variety of antihypertensive
      medications, including diuretics in two children. Linear regression analysis
      revealed that systolic and diastolic blood pressures were directly related to
      calcium and phosphorus intake in black patients. In white children, only dietary
      phosphorus intake and diastolic blood pressure were directly related. There was
      no relationship between sodium intake or GFR and blood pressure in the white or
      black children. PTH levels were directly correlated with systolic and diastolic
      blood pressure in all children. The correlations between PTH and blood pressure
      were stronger in white versus black patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579066
TI  - Low-calcium dialysate stimulates parathormone secretion and its long-term use
      worsens secondary hyperparathyroidism.
AB  - The long-term clinical effects of the use of a low calcium concentration in the
      dialysate are largely unknown. For this reason, the influence of low-calcium
      dialysate on parathyroid hormone (PTH) secretion in hemodialysis patients and its
      long-term effect on the severity of secondary hyperparathyroidism were studied.
      In 35 hemodialysis patients, the dialysate calcium concentration was lowered from
      1.75 to 1.25 mmol/L. Twelve months later, serum iPTH levels increased
      significantly from 18.6 to 33.2 pmol/L and so did alkaline phosphatase levels,
      from 210 to 330 IU/L, without significant changes in serum calcium or phosphorus
      levels. Hemodialysis with low-calcium dialysate (1.25 mmol/L) induced a net
      calcium loss in 10 patients, without modifications in ionized serum calcium
      levels. In addition, mean serum iPTH increased 20% over baseline levels, reaching
      the maximal level at 30 min after the start of hemodialysis with low-calcium
      dialysate. In contrast, mean serum iPTH levels drop dramatically at 30 min of
      hemodialysis with high-calcium dialysate (1.75 mmol/L). It was concluded that low
      calcium dialysate worsens secondary hyperparathyroidism in hemodialysis patients,
      probably by inducing a negative calcium balance and causing repetitive
      stimulation of PTH secretion in each dialysis. The maintenance of normal serum
      calcium levels could be due to PTH-induced calcium mobilization from bone.

PMID- 7579067
TI  - Therapy of membranous nephropathy: use of low-protein diet.

PMID- 7579068
TI  - The Heymann nephritis antigenic complex: megalin (gp330) and RAP.
AB  - Heymann nephritis (HN) has been extensively studied as a model of human
      membranous nephropathy since it was first described by Heymann in 1959. HN was
      induced in active form by the immunization of rats with antigens derived from the
      proximal tubule brush border, resulting in subepithelial glomerular immune
      deposits. HN was also induced passively by the injection of antibrush border
      antibodies into normal rats. A breakthrough in the understanding of the
      pathogenesis of HN was made in the 1970s, when it was established that the
      disease was due to the binding of circulating antibodies to glomerular
      components. This in turn led to a search to identify the endogenous antigen(s).
      In 1982, gp330 (now called megalin), a glycoprotein located in clathrin-coated
      pits of glomerular and proximal tubular epithelia, was identified as a target
      antigen. In 1990, a second protein (44 kd), now known as RAP (for receptor
      associated protein), that binds to megalin was also shown to be a target antigen.
      Both molecules have been cloned and sequenced, and their role in normal
      epithelial cells has been explored. It has come to light that megalin (gp330) is
      a member of the low-density lipoprotein receptor gene family and functions as a
      multiligand receptor for the uptake of a variety of macromolecules (plasminogen,
      protease: protease inhibitor complexes, apolipoprotein E-enriched very low
      density lipoproteins, lactoferrin, among others). RAP associates with megalin and
      appears to function as a chaperone assisting in the folding of megalin in the
      endoplasmic reticulum and its transport to the cell surface. This review
      considers what is now known about the structure, function, and trafficking of
      megalin and RAP and the role of these two molecules in the pathogenesis of HN.

PMID- 7579069
TI  - Acute renal failure due to acetaminophen ingestion: a case report and review of
      the literature.
AB  - Acetaminophen is the most commonly reported drug overdose in the United States.
      Acute renal failure occurs in less than 2% of all acetaminophen poisonings and
      10% of severely poisoned patients. At the therapeutic dosages, acetaminophen can
      be toxic to the kidneys in patients who are glutathione depleted (chronic alcohol
      ingestion, starvation, or fasting) or who take drugs that stimulate the P-450
      microsomal oxidase enzymes (anticonvulsants). Acute renal failure due to
      acetaminophen manifests as acute tubular necrosis (ATN). ATN can occur alone or
      in combination with hepatic necrosis. The azotemia of acetaminophen toxicity is
      typically reversible, although it may worsen over 7 to 10 days before the
      recovery of renal function occurs. In severe overdoses, renal failure coincides
      with hepatic encephalopathy and dialysis may be required. Recognition of
      acetaminophen nephropathy requires the following: (1) a thorough drug history,
      including over-the-counter medications such as Tylenol or Nyquil; (2) knowledge
      of the risk factors that lessen its margin of safety at therapeutic ingestions,
      i.e., alcoholism; and (3) consideration of acetaminophen in the differential
      diagnosis of patients who present with combined hepatic dysfunction and ATN.

PMID- 7579070
TI  - Transmission of cancer with cadaveric donor organs.
AB  - A case is presented in which each of the recipients of a pair of cadaveric
      kidneys developed metastatic carcinoma. One of the recipients died, and the other
      demonstrated involution of metastatic deposits after graft nephrectomy and
      withdrawal of immunosuppression. By the use of polymerase chain reaction of
      minisatellite regions of donor and recipient DNA, the donor origin of the tumor
      was conclusively demonstrated. Although a relatively uncommon complication of
      cadaveric renal transplantation, the transmission of cancer with cadaveric organs
      may become more frequent as older donors are accepted for organ donation.

PMID- 7579071
TI  - Megalin (gp330) possesses an antigenic epitope capable of inducing passive
      Heymann nephritis independent of the nephritogenic epitope in receptor-associated
      protein.
AB  - The Heymann nephritis antigenic complex (HNAC) consists of two glycoproteins,
      megalin (gp330), and the receptor-associated protein (RAP). HNAC is expressed on
      the surface of the glomerular epithelium where it plays a primary role in the
      pathogenesis of Heymann nephritis (HN). Several models were previously proposed
      describing how antibody binding epitopes in HNAC may contribute to the initiation
      and progression of HN. Although these models suggest that nephritogenic epitopes
      capable of initiating HN are present in both megalin and RAP, the structural
      relationship between these epitopes has not been established. Previously a
      nephritogenic epitope was identified and characterized in RAP that initiates
      immune complex formation in HN. In this report, the immunologic relationship
      between nephritogenic epitopes in megalin and RAP were examined to determine
      whether these epitopes are immunologically distinct or antigenically related. To
      this end, a polyclonal antibody to megalin was generated that does not recognize
      RAP by immunoblotting or immunoprecipitation and whether this antibody is capable
      of inducing passive HN was determined. It was found that antimegalin antibodies
      devoid of RAP cross-reactivity induced the formation of subepithelial immune
      deposits (passive HN) when injected into rats. Antibodies eluted from glomeruli
      of the injected rats recognized only megalin by immunoblotting a cortical extract
      and did not recognize a RAP fusion protein or any other renal protein. In
      addition, the eluted antibodies immunoprecipitated two proteolytic fragments of
      megalin (140 and 75 kd) identifying a pathogenic epitope within a smaller
      fragment of megalin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579072
TI  - Effects of chronic renal failure on enzymes of energy metabolism in individual
      human muscle fibers.
AB  - In order to improve knowledge about the mechanisms underlying the alterations of
      energy metabolism recently observed in the skeletal muscle of patients suffering
      from chronic renal failure, this study was designed to test (1) whether changes
      in the activity of key enzymes of energy metabolism occur in the muscle of these
      patients, and if so (2) whether the different muscle fiber types are equally
      altered in their metabolic machinery. For this, the maximum activities of 14
      enzymes were measured in individual muscle fibers microdissected from biopsies of
      rectus abdominis muscle obtained from seven normal subjects and seven patients
      with end-stage renal failure before renal replacement therapy. A large decrease
      in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of
      the beta-oxidation pathway, of citrate synthase, which initiates the
      tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes
      to the synthesis of glycogen from lactate, was observed in the three fiber types
      (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch
      glycolytic). A smaller reduction of the activities of phosphofructokinase and/or
      pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch
      oxidative and/or fast-twitch oxidative-glycolytic fibers. These results
      demonstrate that the abnormalities of muscle energy metabolism observed in
      patients with chronic renal failure are due, at least in part, to intrinsic
      changes in the key enzymes of major energy-providing pathways; they also offer a
      satisfactory explanation for the defect of oxidative metabolism recently
      demonstrated in the muscle of these patients.

PMID- 7579073
TI  - Nutritional assessment with bioelectrical impedance analysis in maintenance
      hemodialysis patients.
AB  - Protein energy malnutrition is common among persons with ESRD and contributes
      substantially to morbidity and mortality. The usual methods of nutritional
      assessment, such as anthropometry, can be misleading because of altered tissue
      hydration. Bioelectrical impedance analysis (BIA) has been recommended by some as
      a practical nutritional assessment tool but has not been validated in patients
      with ESRD. Thirty-three stable patients on maintenance hemodialysis were
      evaluated in an ambulatory clinical research center with simultaneous BIA, dual
      energy x-ray absorptiometry, and deuterium oxide (D2O) and sodium bromide (NaBr)
      isotope dilution studies. Standard determinations of total body water (TBW) and
      body cell mass (BCM) were obtained and compared with values estimated by BIA. Two
      separate outpatient BIA measurements were also obtained approximately 2 wk before
      and after the clinical research center evaluation. BCM estimated by BIA was
      directly correlated (r = 0.92, P < 0.0001) with BCM determined by DEXA and NaBr.
      TBW estimated by BIA was directly correlated (r = 0.96, P < 0.0001) with TBW
      determined by deuterium oxide dilution. The reactance to resistance ratio (Xc/R)
      derived from BIA was inversely correlated (r = -0.73, P < 0.0001) with the
      extracellular water/TBW ratio determined by NaBr/D2O. Bland-Altman analyses
      showed that for TBW, BIA was in excellent agreement with D2O dilution. BCM was
      modestly underestimated by BIA compared with the dual-energy x-ray
      absorptiometry/NaBr standard and was adjusted by linear regression. The
      coefficients of variation on repeated BIA measurements were below 4%,
      demonstrating test-retest reliability. BIA is a valid and reliable method of
      nutritional assessment in maintenance hemodialysis patients.

PMID- 7579074
TI  - Total body nitrogen as a prognostic marker in maintenance dialysis.
AB  - In order to assess long-term nutritional adequacy, 154 patients on maintenance
      dialysis (78 on hemodialysis (HD), 76 on continuous ambulatory peritoneal
      dialysis (CAPD)) underwent measurement of total body nitrogen (TBN) with
      concurrent recording of dietary history, anthropometrics, and serum albumin.
      Seventy-one patients were reassessed 23.3 +/- 2.2 (5 to 76) months later. In
      cross-sectional analyses, anthropometric measurements and dietary intake remained
      stable over time in all patients. However, a significant fall in TBN occurred in
      the HD population with increasing time on dialysis (P < 0.05). In the prospective
      analyses, CAPD patients (N = 26) had a significant increase in TBN (P < 0.02). In
      contrast, longitudinal measurements of TBN in HD patients (N = 36) tended to fall
      but did not reach significance (P = 0.18). TBN correlated with total caloric
      intake estimated from the dietary history (P < 0.05), but not with estimated
      protein intake. During follow-up, 38 patients died. These patients were older (P
      < 0.05), and in the CAPD population, they had been on dialysis for a longer time
      (P < 0.05). Those who died had a lower TBN expressed both as grams per kilogram
      lean body mass (P < 0.005) and as the nitrogen index (P < 0.05). The probability
      of death within 12 months in the patients with a nitrogen index (ratio of the
      measured nitrogen to the predicted nitrogen for a sex-, age-, and height-matched
      control) less than 80% of the predicted normal value was 48%. The relative risk
      of death in this population was 4.1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579075
TI  - Nitric oxide inhibits sodium reabsorption in the isolated perfused cortical
      collecting duct.
AB  - Indirect evidence suggests that nitric oxide inhibits sodium reabsorption by the
      collecting duct; however, direct evidence is lacking. It was hypothesized that
      endothelium-derived nitric oxide inhibits sodium flux in the cortical collecting
      duct by blocking amiloride-sensitive sodium channels. Tubules were obtained from
      Sprague-Dawley rats pretreated with deoxycorticosterone acetate (5 mg/rat i.m.) 5
      to 9 days before the experiment. Nitric oxide was added to the system by either
      the addition of endothelial cells and the induction of the release of nitric
      oxide via acetylcholine (10(-7) M) or by the addition of nitric oxide donors.
      Acetylcholine-induced nitric oxide release from endothelial cells decreased lumen
      to-bath sodium flux by 24 +/- 7% (N = 3; P < 0.05). The addition of the nitric
      oxide donor, spermine NONOate (10(-5) M), decreased net sodium flux 68% from 10.1
      +/- 2.0 to 3.6 +/- 2 pmol/mm.min (N = 5; P < 0.025). To assure that the
      inhibition of sodium flux was due to nitric oxide, another donor, nitroglycerin
      (2 x 10(-5) M), was used, which decreased sodium flux by 43%. Luminal amiloride
      (10 microM) decreased net sodium flux by 83% (from 14.8 +/- 1.2 to 2.4 +/- 0.7
      pmol/mm.min; N = 5; P < 0.025). The addition of nitric oxide via spermine NONOate
      to tubules decreased intracellular sodium levels by 26% (N = 6; P < 0.005). The
      Na(+)-K+ATPase activity of spermine NONOate-treated tubules was 14.7 +/- 3.2
      pmol/mm.min compared with the control value of 10.2 +/- 2.0 pmol/mm.min.
      Nitroglycerin did not significantly affect pump activity either.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579077
TI  - Continuous ambulatory peritoneal dialysis--quo vadis?

PMID- 7579076
TI  - Angiotensin II stimulates interleukin-6 release from cultured mouse mesangial
      cells.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine exerting a wide variety of
      biologic responses, including cell proliferation. Recently, IL-6 has been known
      to play a role in the pathogenesis of mesangial proliferative glomerulonephritis.
      IL-6 is now recognized as an autocrine growth factor for glomerular mesangial
      cells, and various inflammatory mediators have been shown to promote IL-6 release
      from mesangial cells. However, little is known about the noninflammatory stimuli
      of IL-6 release from mesangial cells. In this study, it was hypothesized that
      angiotensin II (AngII) is one of the noninflammatory mediators of IL-6 release in
      mesangial cells, and the effects of AngII on IL-6 release and mRNA expression in
      cultured mouse mesangial cells (CMMC) were investigated. It was demonstrated that
      AngII (10(-7) M or higher) caused IL-6 release and mRNA accumulation in CMMC. IL
      6 release was detected at 4 h and reached a plateau at 8 h after the addition of
      AngII, whereas IL-6 mRNA expression peaked at 4 h. The effects of AngII on IL-6
      release and gene expression were completely blocked by the AngII receptor type 1
      (AT1 receptor) antagonist CV-11974. AngII and IL-6 were both shown to stimulate
      DNA synthesis in CMMC, and the blockade of IL-6 signaling with anti-IL-6 receptor
      antibody abolished the enhanced DNA synthesis induced by AngII. These results
      raise a possibility that the growth-promoting effect of AngII on mesangial cells
      is at least partially mediated by IL-6 released from mesangial cells.

PMID- 7579078
TI  - The elderly patient with acute renal failure.
AB  - Structural and functional changes observed in the aging kidney predispose the
      elderly patient to acute renal failure. Up to 36% of the patients with acute
      renal failure from this institution were over 70 yr, and the literature is full
      of similar experiences. The elderly patient with abrupt cessation of adequate
      renal function requires a special work-up in diagnosis and treatment. Prerenal
      and obstructive causes are of particular interest. Although the question of
      whether or not age has an independent prognostic importance during an episode of
      acute renal failure remains debated; when these and other authors compared the
      outcome of young and old populations with these disorders, a similar evolution
      was always observed. Age should not be used as a discriminant factor in
      therapeutic decisions concerning acute renal failure.

PMID- 7579080
TI  - Cholesterol emboli presenting as acute allograft dysfunction after renal
      transplantation.
AB  - Cholesterol emboli are a common complication of atherosclerotic vascular disease.
      A 40-yr-old renal transplant recipient who developed acute allograft dysfunction
      1 day after the initiation of cyclosporine therapy and 6 days after
      transplantation is described. A renal allograft biopsy revealed cholesterol
      emboli in interlobular arteries and in glomeruli. Four previously reported cases
      of cholesterol emboli in renal allografts are described, and the cause and
      pathogenesis of atheroembolic disease are reviewed. Atheroemboli causing injury
      to the renal allograft may arise from either donor or recipient vessels.
      Vigilance for the occurrence of these emboli needs to be maintained when donor or
      recipient vessels demonstrate evidence of significant atherosclerotic vascular
      disease.

PMID- 7579081
TI  - Glomerulonephritis with associated hypocomplementemia and crescents: an unusual
      case of fibrillary glomerulonephritis.
AB  - Fibrillary glomerulonephritis is an unusual, but not rare cause of
      glomerulonephritis. Hypocomplementemia in association with fibrillary
      glomerulonephritis has been reported only once previously. A patient with
      hypocomplementemia and fibrillary deposits as demonstrated by electronmicroscopy
      is reported. The clinical and pathologic features of fibrillary
      glomerulonephritis and immunotactoid glomerulopathy are reviewed.

PMID- 7579079
TI  - Amphotericin B nephrotoxicity: the adverse consequences of altered membrane
      properties.
AB  - Amphotericin B (AmB) has been in clinical use for more than 30 yr but has
      remained the most effective drug for treatment of serious fungal infections. Its
      use has increased in recent years, as the result of increases in aggressive
      intensive care support and increased numbers of immunocompromised patients.
      Nephrotoxic manifestations are common, and this is the major factor limiting the
      clinical use of the drug. A number of recent studies have contributed to a better
      understanding of the mechanism by which AmB exerts its nephrotoxic effect. AmB
      alters cell membrane permeability and probably as a consequence alters tubular
      and vascular smooth muscle cell function, leading to various tubular transport
      defects and vasoconstriction. Decreased RBF appears to play a major role in AmB
      induced reduction GFR, and recurrent ischemia may be the basis of permanent
      structural nephrotoxic effects. Salt loading is the only measure proven by
      controlled prospective study to ameliorate AmB nephrotoxicity in humans.
      Liposomal AmB and the formulation of an emulsion of AmB in lipid may provide a
      protective effect based on altering the affinity of AmB for mammalian cell
      membranes, while preserving high efficacy against fungal cells. However, further
      studies are needed to evaluate the efficacy and safety of these new AmB
      formulations.

PMID- 7579082
TI  - A comparison of mortality between patients treated with hemodialysis and
      peritoneal dialysis.
AB  - Patients with ESRD treated with dialysis have a high mortality rate. Controversy
      exists as to whether this high mortality rate is affected by modality choice. The
      purpose of this epidemiologic study was to compare mortality in prevalent
      hemodialysis-treated (HD) and peritoneal dialysis-treated (PD) patients in a
      large national sample, adjusting for demographic characteristics. Data were
      obtained from the U.S. Renal Data System for patients prevalent on January 1 of
      the years 1987, 1988, and 1989, each with 1 yr of follow-up. Patients were
      censored at transplantation. Death rates per 100 patient years were compared
      between HD and PD, adjusting for age, race, gender, cause of ESRD (diabetes
      versus nondiabetes) and < 1 yr or > 1 yr of prior ESRD, by the use of Poisson
      regression. There were 42,372 deaths occurring over 170,700 patient years at
      risk. On average, prevalent patients treated with PD had a 19% higher adjusted
      mortality risk (relative risk (RR) = 1.19; P < 0.001) than did those treated with
      HD. This risk was found to be insignificant (P > 0.05) and small for ages < 55
      and increasingly large and significant for ages > 55 yr. It was accentuated in
      diabetics (RR = 1.38; P < 0.001) but was also present in nondiabetics (RR = 1.11;
      P < 0.001). Although present in both males and females, this risk was accentuated
      in females (RR = 1.30 versus 1.11; both P < 0.001). In this national study of
      prevalent U.S. dialysis patients, treatment assignment to PD was associated with
      a 19% higher all-cause mortality rate than HD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579083
TI  - A comparison of cause of death between patients treated with hemodialysis and
      peritoneal dialysis.
AB  - Mortality rates associated with peritoneal dialysis (PD) have been found to be
      higher than those associated with hemodialysis (HD) among prevalent U.S. patients
      over the age of 55 in the preceding study. Given the substantial technical
      differences between PD and HD, causes of death might also be expected to differ
      between these dialytic modalities. In order to help elucidate the relative
      contributions of these technical differences and to further the understanding of
      the excess mortality observed among PD-treated dialysis patients, this
      epidemiologic study compared cause of death in prevalent HD- and PD-treated
      patients in a large national sample, adjusting for demographic characteristics.
      Data for patients prevalent on January 1 of the years 1987, 1988, and 1989, each
      with 1 yr of follow-up, were obtained from the U.S. Renal Data System. Patients
      were censored at transplantation. Death rates per 100 patient years for seven
      cause-of-death categories were compared between HD and PD, adjusting for age,
      race, gender, cause of ESRD (diabetes versus nondiabetes), and < 1 yr or > 1 yr
      of prior ESRD, by use of the Poisson regression. There were 42,372 deaths
      occurring over 170,700 patient years at risk. There was a significantly increased
      mortality risk for PD compared with HD for all cause-of-death categories, except
      malignancy, for which there was a higher mortality risk for HD. The excess all
      cause mortality observed in PD-treated patients can be accounted for, in
      decreasing order, by infection (35%), acute myocardial infarction (24%), other
      cardiac causes (16%), cerebrovascular disease (8%), withdrawal (8%), and
      malignancy (-6%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579085
TI  - Symptomatic fluid retention in patients on continuous peritoneal dialysis.
AB  - The clinical features, pathogenesis, management, prognosis, and predictors of
      symptomatic fluid gain (SFR) were analyzed for 71 episodes occurring in 66
      patients on continuous peritoneal dialysis, 94.4% on continuous ambulatory
      peritoneal dialysis (CAPD) and 5.6% on continuous cycling peritoneal dialysis.
      Compared with a control group of 149 CAPD patients, the SFR group had a higher
      percentage of diabetics (64 versus 46%) and a higher frequency of noncompliance
      with fluid restriction (76 versus 22%), salt restriction (74 versus 23%), and
      performance of dialysis (30 versus 7%) (all at P < or = 0.015). Peripheral edema
      (100%), pulmonary congestion (80%), pleural effusions (76%), and systolic (83%)
      and diastolic (66%) hypertension were the most common manifestations of SFR. The
      annual hospitalization rate for SFR was 4.1 +/- 5.8 days per patient. SFR
      resulted in the discontinuation of CAPD in 10 patients and death in 1 patient.
      Serum sodium concentration was not different between dry and maximal weight in
      the SFR group. Thirty-eight (58%) of SFR and 61 (41%) of control patients were
      evaluated by peritoneal equilibration tests (PET). SFR patients had lower PET
      drain volume (2.08 +/- 0.47 versus 2.54 +/- 0.23 L) and a higher frequency of
      high peritoneal solute transport (32.2 versus 2.4%). In this group, logistic
      regression identified dietary noncompliance, low PET drain volume, and young age
      as independent predictors of SFR. Response to management and preventive measures
      was inconsistent. The best results were obtained by the use of short dwell
      exchanges with hypertonic dialysate in compliant patients with high peritoneal
      solute transport. SFR has serious consequences in CAPD. (ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7579086
TI  - Intracellular acidification mediates the inhibitory effect of peritoneal
      dialysate on peritoneal macrophages.
AB  - Commercial peritoneal dialysis solution (CDS) is known to have a detrimental
      effect on the capacity of peritoneal macrophages (PM phi) to kill bacteria and
      produce acute phase cytokines. This cytotoxic effect is largely caused by the low
      pH of CDS. Because the cytoplasmic pH (pHi) is an important determinant of
      cellular function, the effect of CDS on the pHi of PM phi from continuous
      ambulatory peritoneal dialysis patients was studied. The pHi of PM phi was
      measured fluorometrically in N-hydroxyethylpiperazine-N'-2-ethanesulfonic acid
      (HEPES)-buffered salt solution (HBSS) or CDS at pH values of 5.3, 6.5, and 7.0,
      values that represent the pH existing in dialysate during the first 30 min of
      dwell time. For any given pH of the experimental medium, the pHi was always more
      acidic in CDS than in HBSS. When PM phi were incubated with a lactate-containing
      HBSS, a cellular acidification was observed that was similar to that attained by
      exposure to CDS at the same pH. This supports the hypothesis that the decrease in
      pHi was due to the influx of lactic acid from the CDS into the PM phi. In order
      to demonstrate a causal association between the CDS-induced cellular
      acidification and a defect in phagocytosis and cytokine production, these
      functions were studied after pHi clamping by means of K+/nigericin. It was found
      that clamping pHi to values below 6.5 led to a markedly reduced tumor necrosis
      factor-alpha production and phagocytosis. However, at values of pHi > 6.5, these
      functions were normal. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579087
TI  - Determination of circulating blood volume by continuously monitoring hematocrit
      during hemodialysis.
AB  - Dialysis-induced hypovolemia occurs because the rate of extracorporeal
      ultrafiltration exceeds the rate of refilling of the blood compartment. The
      purpose of this study was to evaluate a method for calculating circulating blood
      volume (BV) during hemodialysis (HD) from changes in hematocrit (Hct) shortly (2
      to 10 min) before and after ultrafiltration (UF) was abruptly stopped. Hct was
      monitored continuously during 93 HD treatment sessions in 16 patients by an
      optical technique and at selected times by centrifugation of blood samples. Total
      plasma protein and albumin concentrations were also measured at selected times.
      Continuously monitored Hct correlated with Hct determined by centrifugation (R =
      0.89, N = 579). Relative changes in BV determined by continuously monitored Hct
      were not different from those determined by total plasma protein concentration (P
      = 0.05; N = 273). Calculated BV at the start of dialysis (4.1 +/- 1.3 L) was not
      different (P = 0.18, N = 12) from that derived anthropometrically from the
      patient's dry weight (4.6 +/- 0.8 L), and calculated BV when UF was stopped was
      3.2 +/- 0.5 L (46 +/- 7 ml/kg body wt). These latter estimates of BV are
      consistent with those determined previously by dilution techniques in HD
      patients. It was concluded that (1) relative changes in BV assessed by
      continuously monitored Hct were unbiased and (2) BV can be determined
      noninvasively during HD by continuously monitoring Hct and temporarily stopping
      UF.

PMID- 7579084
TI  - Sleep disorders in patients on continuous ambulatory peritoneal dialysis.
AB  - Sleep complaints, habits, and medical history were surveyed in 81 patients
      chronically receiving continuous ambulatory peritoneal dialysis. Seventy-three
      percent of the sample reported insomnia, and 52% reported unintentional napping
      during the day. Behavioral factors (such as caffeine or alcohol use) or the
      severity of concurrent medical disease did not account for the sleep problems.
      Eighteen of these patients subsequently underwent polysomnography and objective
      measurement of daytime sleepiness. Clinically significant sleep apnea syndrome
      was present in 11. The presence of sleep apnea was associated with increased
      levels of psychological distress and daytime sleepiness. Periodic leg movements
      during sleep were also frequently observed but had minimal effect on sleep
      quality. Implications of these findings for clinical practice are discussed.

PMID- 7579088
TI  - Hepatitis C virus infection and membranoproliferative glomerulonephritis in
      Japan.
AB  - The prevalence of hepatitis C virus (HCV) infection was determined in 146 adult
      patients with various types of glomerulonephritis and renal diseases monitored
      between 1990 and 1993. Serum HCV antibody (HCV Ab) was evaluated, and positive
      cases were tested for HCV RNA by polymerase chain reaction. HCV infection was
      present in 1 (1.7%) of 58 cases of immunoglobulin A nephropathy, 0 (0%) of 14
      cases of lupus nephritis, 0 (0%) of 12 cases of minimal change nephrosis, and 0
      (0%) of 28 cases of other renal diseases, which is similar to the 2% prevalence
      observed in healthy blood donors in Japan. In contrast, HCV Ab was observed in 2
      (8.3%) of 24 cases of membranous nephropathy and 6 (60%) of 10 cases of
      membranoproliferative glomerulonephritis (MPGN) Type I. The prevalence of HCV
      infection in MPGN patients was significantly higher than the frequency of HCV
      infection observed in the other patients with renal diseases (P < 0.001). HCV RNA
      was present in all cases in which HCV Ab was present. The six patients with HCV
      MPGN were similar to the four patients with idiopathic MPGN with respect to age,
      presence of nephrotic syndrome, and renal dysfunction, but had a higher incidence
      of liver dysfunction, cryoglobulinemia, rheumatoid factor, and hypocomplementemia
      (low C3). HCV infection is present in a large percentage of patients with MPGN in
      Japan and clinically may differ slightly from other cases of MPGN.

PMID- 7579089
TI  - Atrial natriuretic peptide stimulates the expression of transforming growth
      factor-beta in cultured murine mesangial cells: relationship to suppression of
      proliferation.
AB  - Atrial natriuretic peptide (ANP) is a growth suppressor for a variety of
      different cell types including cultured mesangial cells. This study examined the
      effects of ANP on the expression and synthesis of transforming growth factor-beta
      (TGF-beta) in a cultured murine mesangial cell line (MMC). Full-length rat ANP as
      well as 8-bromo-cGMP, but not ring-deleted ANP analogues, induced, in a dose
      dependent manner, TGF-beta 1 mRNA expression in MMC. Moreover, full-length ANP
      and 8-bromo-cGMP stimulated the synthesis and release of TGF-beta 1 into cell
      culture supernatants as measured by a specific enzyme-linked immunosorbent assay
      and mink cell bioassay. The induction of TGF-beta 1 by 10(-6) M ANP and 10(-4) M
      8-bromo-cGMP for 24 h was also documented by western blotting of MMC culture
      supernatants. However, transient transfection studies in MMC with three different
      murine TGF-beta 1 reporter gene constructs revealed only little stimulation of
      activity after ANP treatment, suggesting that posttranscriptional activation may
      mainly contribute to TGF-beta mRNA induction. Functional studies demonstrated
      that the ANP-mediated inhibition of mitosis, induced by 5% fetal calf serum, is
      partly abolished in the presence of a neutralizing anti-TGF-beta 1-3 antibody. In
      addition, the antiproliferative effects of exogenous 8-bromo-cGMP are also
      attenuated by anti-TGF-beta 1-3 antibody. These findings indicate that ANP
      stimulates TGF-beta expression in MMC and that the antiproliferative effects of
      ANP in this cell line may be mediated, at least to some extent, by the endogenous
      induction of TGF-beta. An increase in intracellular cGMP is most likely the
      mediator of this TGF-beta 1 induction. Considering the fibrogenic effects of TGF
      beta, these findings may be important in the development of glomerulosclerosis in
      situations with an increase in local or systemic ANP.

PMID- 7579091
TI  - Pharmacokinetics of fluconazole in renal failure.
AB  - Fluconazole (FLU) is a widely used antifungal agent. The multiple-dose
      pharmacokinetics of FLU in renal impairment have not been previously
      investigated. The following groups were studied: volunteers with creatinine
      clearances (CLcr, > 50 mL/min) of 107 mL/min, given a loading dose of 400 mg and
      a daily dose of 200 mg/day for 9 days (Group 1); subjects with CLcr between 21
      and 50 mL/min with a mean of 38 mL/min, given a loading dose of 200 mg and a
      maintenance dose of 100 mg/day for 9 days (Group 2); subjects with CLcr between
      11 and 20 mL/min with a mean of 14.8 ml/min, given a loading dose of 100 mg and a
      maintenance dose of 50 mg/day for 9 days (Group 3); and subjects on hemodialysis
      (three times per week) receiving a loading dose of 200 mg and then 100 mg after
      each of four dialysis sessions (Group 4) (N = 10 per group). After the
      administration of the loading dose on Day 1, the mean area under the curve (AUC)
      (0-24) measurements were approximately proportional to the dose of FLU and
      independent of renal function. After 10 days of FLU dosing, the mean renal
      clearance of FLU decreased as CLcr decreased for Groups 1 to 3, and the Day 10
      mean half-lives were inversely related to mean CLcr (36.7 h in Group 1, 84.5 h in
      Group 2, and 101.9 h in Group 3). The mean AUC (0-24) on Day 10 was similar for
      Group 1 compared with Group 2, despite a reduction in the maintenance dose by
      50%. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579090
TI  - The role of a complement regulatory protein in rat mesangial glomerulonephritis.
AB  - The host cells are protected from the indiscriminate attack of homologous
      complement by the membrane-associated complement regulatory proteins. A mouse
      monoclonal antibody (mAb) 512 (immunoglobulin G1 subclass) has recently been
      described that recognizes and inhibits the function of a rat complement
      regulatory protein, a rat homologue of mouse Crry/p65. The aim of this work is to
      assess the role of a complement regulatory protein (512Ag) recognized by mAb 512
      in the complement-dependent glomerular injury induced by mAb OX7 against rat Thy
      1.1. For the induction of mesangial injury, the left kidney of a rat was perfused
      with a combination of OX7 and 512 and the perfusate was discarded from the renal
      vein (Group I). After the renal artery and vein were restored, the left kidney
      was connected to the systemic circulation. Rats were euthanized 3 h, 2 days, and
      14 days later. Rats perfused either with OX7 (Group II) or with 512 (Group III)
      or with vehicle only (Group IV) were used as controls. At 3 h, rats of Group I
      showed more prominent cellular infiltration and mesangial lysis and more C3
      deposition in the glomeruli than rats of Group II. Rats of Groups III and IV
      showed no significant changes. At Day 2, there was still significant mesangial
      lysis and leukocyte infiltration in Group I rats, whereas rats in other groups
      showed an almost normal appearance. Glomerular injury in Group I rats returned to
      normal by Day 14.

PMID- 7579092
TI  - Renal papillary necrosis--a sixteen-year clinical experience.
AB  - This study sought to characterize patients with renal papillary necrosis seen at
      one tertiary referral center by reviewing medical records of patients with a
      confirmed diagnosis between January 1, 1976 and September 1, 1992. One hundred
      sixty-five cases were identified. The mean age at diagnosis was 57 yr (SD 15).
      The female-to-male ratio was 1.1:1.0. Ninety-two percent of patients were white.
      Seventy-seven percent of cases were unsuspected before diagnosis, and 16% were
      diagnosed at autopsy. The most common associated conditions were urinary tract
      infection, analgesic abuse, urinary tract obstruction, diabetes mellitus, and
      sickle cell disease. There was considerable overlap in the presence of these
      conditions, with two or more identified in 36% of patients. In addition, 11% of
      patients had none of these well-recognized risks. Other diagnoses in this group
      included lupus nephritis, Wegener's granulomatosis, and renal artery stenosis. A
      decline in case numbers of approximately 50% was demonstrated over the last 10 yr
      studied. This period was associated with a 57% reduction in the number of
      excretory urograms carried out, suggesting that changes in diagnostic imaging
      preference may have contributed. Vital status and renal outcome data after
      diagnosis were obtained in 93% of cases. Of those diagnosed while living,
      survival was lowest among diabetic patients. Ten-year survival for nondiabetics
      was not significantly different from the expected survival of an age- and sex
      matched cohort. The overall risk for requiring renal replacement therapy after
      the diagnosis of renal papillary necrosis in surviving patients was low (7% of
      136 patients at risk).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579093
TI  - Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration
      rate.
AB  - Renal clearance of inulin is the best available indicator of GFR but cannot be
      used routinely for clinical purposes and is also difficult to perform for
      clinical investigation when repeated measurements are required. The aim of this
      study was to find a reliable alternative to inulin clearance that would allow one
      to avoid the use of radioactivity and problems related to the continuous infusion
      of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast
      agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per
      1.73 m2) underwent simultaneous measurements of renal clearance of inulin and
      plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood
      samples were drawn up to 600 min after the administration. Iohexol concentrations
      (by HPLC) were analyzed by a two-compartment, open-model system. A highly
      significant correlation between the plasma clearance of iohexol and the renal
      clearance of inulin over a wide range of GFR values was found. By analyzing the
      data with a simplified method that uses a one-compartment model corrected with
      the Brochner-Mortensen formula, an excellent correlation with the inulin
      clearance was also observed. When only patients with moderate to severe renal
      failure were considered, a significant correlation between the two methods was
      found. A further comparison between GFR determined with iohexol and iopromide, a
      new low-osmolarity, low-viscosity contrast medium, was also performed in a
      subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579094
TI  - Mutation in alpha 5(IV) collagen chain gene in nonfamilial hematuria.
AB  - Alport syndrome is an inherited disorder characterized by progressive nephritis
      with ultrastructural basket-weave changes of the glomerular basement membrane and
      neurosensory deafness. Mutations in the COL4A5 gene encoding the Type IV collagen
      alpha 5 chain have been reported to occur in patients with X-linked Alport
      syndrome. A girl with hematuric nephritis, characteristic basket-weave glomerular
      basement membrane changes, and abnormal expression of the Type IV collagen alpha
      5 chain immunohistochemically, but no family history of nephritis, was
      identified. Mutation detection enhancement gel electrophoresis of the polymerase
      chain reaction-amplified exons of COL4A5 from this patient revealed a sequence
      variant in the exon 50 region. Sequence analysis of her polymerase chain reaction
      product demonstrated a single-base (C; nucleotide 4728 from the 5' end) deletion
      in exon 50. This novel mutation alters the reading frame and introduces a
      translation stop codon that would be expected to result in a noncollagenous
      domain with only 209, instead of the normal 229, amino acid residues. Gene
      tracking with restriction enzyme AfIIII demonstrated that her mother was normal.
      These findings represent a new mutation of the X-linked Alport syndrome in this
      patient and demonstrate that a COL4A5 gene mutation causes the abnormal
      expression of Type IV collagen alpha 5 chain protein.

PMID- 7579095
TI  - Metabolic studies of rat renal tubule cells loaded with cystine: the cystine
      dimethylester model of cystinosis.
AB  - The cause of Fanconi syndrome in cystinosis is enigmatic. It has previously been
      shown that renal tubules could be loaded with cystine by incubating them with
      cystine dimethylester (CDE), mimicking the biochemical hallmark of cystinosis.
      Such tubules have impaired transport, decreased whole-cell O2 consumption, and
      substrate utilization. In this study, the metabolic disturbances in cystine
      loaded renal tubule cells were further characterized. Isolated rat renal tubules
      were loaded with cystine by incubating them with 2 mM CDE for 10 min. This had no
      significant effect on total ATPase, Na(+)-K(+)-ATPase, or the ouabain-insensitive
      ATPase activity of renal tissue homogenates from these cystine-loaded tubules.
      Intracellular K was significantly lower in the cystine-loaded tubules (37 +/- 2
      versus 47 +/- 3 nEq/mg; P < 0.008). Intracellular ATP was reduced by 39% in the
      cystine-loaded tubules (23.7 +/- 2.4 versus 38.1 +/- 3.3 nmol/mg of protein; P <
      0.0025). CDE (2 mM) reduced isolated mitochondrial O2 consumption with glutamate
      as the substrate by 66% (4.7 +/- 0.7 versus 13.9 +/- 0.8 nm/min per mg of
      protein, P < 0.001) but had no effect on mitochondrial O2 consumption with
      succinate as the substrate. It was speculated that the impaired transport from
      cystine loading with CDE is secondary to a decrease in energy generation.

PMID- 7579096
TI  - Hypocalcemia after an acute phosphate load is secondary to reduced calcium efflux
      from bone: studies in patients with minimal renal function and varying
      parathyroid activity.
AB  - Seven patients with severe hyperparathyroidism secondary to chronic renal
      failure, six patients with hypoparathyroidism after remote total
      parathyroidectomy also with chronic renal failure, and a miscellaneous group of
      three patients, some of whom were in the previous two groups, were studied on 24
      occasions over a 6-h period. Each test consisted of a 2-h control period followed
      by a 4-h phosphate (Pi) infusion period. Radioactive calcium, 45Ca, had been
      administered the evening before. Samples were taken every 15 min throughout the 6
      h study. In all tests, ionized and total calcium fell as Pi rose. Intact
      parathyroid hormone levels (PTH) rose, except in the hypoparathyroid patients, in
      whom there was no change. The decline in 45Ca activity was not affected by the Pi
      infusion, the fall being -0.131 +/- 0.057 cpm/min during the control period and 
      0.124 +/- 0.043 during the Pi infusion. There were no changes in pH, bicarbonate,
      electrolytes, or vitamin D metabolites during the procedure. The mean overall
      fall in total calcium was -0.118 mmol/mmol rise in Pi. For ionized calcium, it
      was -0.067 mmol/mmol Pi or 56.8% of the total calcium. This ratio was unchanged
      throughout the test period. With a steady flux of calcium from extracellular
      fluid (ECF) to bone as measured by 45Ca, the fall in ECF calcium has to be due to
      a decreased flux from bone to ECF. This could be produced by the reduced
      dissolution of a labile pool of a calcium salt such as brushite, CaHPO4.

PMID- 7579097
TI  - Intragraft T cell receptor transcript expression in human renal allografts.
AB  - Allograft rejection is a T cell-dependent process. It is not known whether
      rejection is mediated by a limited number of T cell clones or by a polyclonal
      population of T cells. Several studies attempting to answer this question using
      molecular techniques to analyze the T cell receptor (TCR) population have reached
      conflicting conclusions. Reverse transcription-assisted polymerase chain reaction
      (PCR) has been used to quantify T cell infiltration and examine TCR heterogeneity
      in kidney transplant biopsies from patients experiencing graft dysfunction. RNA
      from snap-frozen biopsies gathered on 23 transplant patients was reverse
      transcribed to cDNA and used as the template for PCR. The constant region gene of
      the TCR beta chain (C beta), 22 different variable region genes of the TCR beta
      chain (V beta) and the constitutively expressed glyceraldehyde phosphate
      dehydrogenase (GAPD) gene were amplified. T cell infiltration, as estimated by
      the ratio of reverse-transcribed cDNA C beta/glyceraldehyde phosphate
      dehydrogenase, was significantly higher in acute cellular rejection (ACR) (2.25)
      than in nonrejection (NR) (0.40, P < 0.05). The number of intragraft V beta
      families was higher in chronic rejection and acute cellular rejection (18 and
      16.4, respectively) than in nonrejection (8.7). Five serial biopsies from two
      patients progressing to immunologic graft loss showed an increase in the number
      of intragraft V beta families. The finding of increased numbers of TCR V beta
      families amplified from acutely and chronically rejecting grafts as compared with
      nonrejecting graft supports the hypothesis that, at the time of clinically
      apparent rejection, there is a polyclonal infilitration of T cells.

PMID- 7579098
TI  - Transforming growth factor-beta and matrix protein expression in acute and
      chronic rejection of human renal allografts.
AB  - Because the increased tissue expression of TGF-beta underlies fibrosis in many
      diseases, it was hypothesized that sustained elevated transforming growth factor
      (TGF)-beta overexpression might be responsible for fibrosis in chronic rejection
      of the renal allograft. To test this hypothesis, biopsies were obtained from 5
      patients with acute rejection, 5 patients with chronic rejection, 10 normal
      individuals, and 10 patients with kidney disease. The tissues were examined by
      immunofluorescence for the three TGF-beta isoforms (1, 2, and 3) and the two
      matrix proteins induced by TGF-beta that serve as markers of fibrosis:
      fibronectin extradomain A positive (EDA+) and plasminogen activator inhibitor-1
      (PAI-1). The tubulointerstitium from all cases of acute rejection and chronic
      rejection showed highly significant increases in immunostaining for the three TGF
      beta isoforms (P < 0.001), fibronectin EDA+ (P < 0.005), and PAI-1 (P < 0.001).
      In the glomeruli, only TGF-beta 1 expression achieved statistical significance (P
      < 0.005) in acute rejection, whereas in chronic rejection, all three TGF-beta
      isoforms (p < 0.001) in addition to fibronectin EDA+ (p < 0.001) and PAI-1 (p <
      0.001) were elevated. There was both cellular and matrix staining of the TGF-beta
      isoforms. In striking contrast, control kidney tissues were negative or only
      weakly positive. Because TGF-beta was present both in acute and in chronic
      rejection but not in control tissues and because acute rejection episodes are a
      good predictor for chronic rejection, these results suggest that TGF-beta may
      play a role in the pathogenesis of fibrosis in chronic rejection.

PMID- 7579100
TI  - American Society of Nephrology 28th annual meeting. November 5-8, 1995.
      Abstracts.

PMID- 7579099
TI  - Absence of vacuolar H(+)-ATPase pump in the collecting duct of a patient with
      hypokalemic distal renal tubular acidosis and Sjogren's syndrome.
AB  - Distal renal tubular acidosis (dRTA) is a common complication of autoimmune
      connective tissue diseases. The underlying pathophysiology of renal tubular
      acidosis in these syndromes is frequently characterized by impaired hydrogen ion
      secretion, i.e., secretory defect dRTA. However, the precise molecular events
      leading to this disturbance remain poorly understood. An opportunity was recently
      afforded to examine the ultrastructural features of the collecting duct in a
      patient with Sjogren's syndrome and secretory defect dRTA. Immunocytochemical
      analysis of a renal biopsy obtained 12 months after the patient's initial
      presentation demonstrated a complete absence of vacuolar H(+)-ATPase in the
      collecting duct. Antibodies to the 31- and 56-kd kidney-specific subunits of the
      H(+)-ATPase pump were used to characterize pump distribution. Interestingly,
      although antiserum to the CI-:HCO3- anion exchanger (band-3 protein) reacted
      strongly with normal human kidney and the patient's red blood cells, no
      immunoreactivity was observed in the patient's collecting duct epithelium.
      Importantly, electron microscopy of the patient's renal biopsy specimen disclosed
      cells that ultrastructurally were indistinguishable from intercalated cells.
      These results suggest that the functional basis of impaired hydrogen ion
      secretion in this patient was secondary to the absence of intact H(+)-ATPase
      pumps rather than defective pump function or distribution. The presence of
      intercalated cells ultrastructurally, but the absence of discernible staining for
      band-3 protein and H(+)-ATPase, also suggests that the defect in proton secretion
      may represent a defect involving the assembly of at least two of the ion
      transport pumps essential for the normal maintenance of acid-base homeostasis by
      the intercalated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579101
TI  - Bedside coagulation monitoring.

PMID- 7579102
TI  - Determination of normal versus abnormal activated partial thromboplastin time and
      prothrombin time after cardiopulmonary bypass.
AB  - OBJECTIVE: The study's objective was to determine the prothrombin time (PT) and
      activated partial thromboplastin time (aPTT) values that differentiated normal
      from excessively bleeding patients immediately after cardiopulmonary bypass
      (CPB). DESIGN: A prospective blinded study. SETTING: A large academic medical
      center. PARTICIPANTS: 148 patients were studied. INTERVENTIONS: aPTT and PT were
      determined by the hospital laboratory and the Biotrack 512 Coagulation Monitor
      (Ciba Corning Diagnostics, Medfield, MA) from an arterial whole blood sample
      obtained 10 minutes after protamine administration. Patients were subjectively
      and objectively defined as "bleeders" or "nonbleeders" with blinded observers.
      MEASUREMENTS AND MAIN RESULTS: The specificity and sensitivity were determined by
      a receiver operating characteristic (ROC) analysis. Twenty-three of 148 patients
      (14.9%) were characterized as bleeders. The laboratory PT had a maximal
      specificity and sensitivity of 78% and 75%, respectively, at a value of 15.4 s,
      with a negative and positive predictive value of 93% and 33%, respectively. The
      maximal specificity and sensitivity of the laboratory aPTT was 64% and 76%,
      respectively, at a value of 46 s, with a negative and positive predictive value
      of 89% and 33%, respectively. aPTT and PT approached normal values after 12 hours
      in the intensive care unit. CONCLUSION: The aPTT and PT values that produce the
      maximal sensitivity and specificity in the ROC analysis may be helpful to
      differentiate patients who are bleeding excessively from those patients who are
      not after CPB and to guide transfusion of blood products. New whole blood
      coagulation devices with rapid turn-around times had similar predictive value for
      bleeding tendency compared with standardized laboratory tests.

PMID- 7579104
TI  - Comparison of the use of a propofol infusion in cardiac surgical patients with
      normal and low cardiac output states.
AB  - OBJECTIVES: This study compared the hemodynamic effects of a propofol infusion
      with fentanyl analgesia in patients undergoing cardiac surgery with normal and
      low cardiac output states. Low cardiac output was defined as a cardiac index less
      than 2.5 L/min/m2 with a minimum pulmonary capillary wedge pressure of 7 mmHg.
      DESIGN: A prospective and open study. SETTING: A single center cardiothoracic
      unit within a teaching hospital. PARTICIPANTS: Patients were assigned to group P,
      poor cardiac output or group N, normal cardiac output, after thermodilution
      pulmonary artery catheter assessments. INTERVENTIONS: Both groups received a
      propofol infusion, 8 mg/kg/hr, until induction of anesthesia, followed by 4
      mg/kg/hr until the intensive care unit. Fentanyl, 15 micrograms/kg, and
      pancuronium, 0.15 mg/kg, were administered after induction. The lungs were
      ventilated with oxygen. MEASUREMENTS AND MAIN RESULTS: Hemodynamic assessments
      were repeated at intervals until cardiopulmonary bypass. Changes within and
      between groups were compared using t tests on percentage change from baseline.
      Group N had significantly greater decreases in cardiac index, stroke volume, and
      left ventricular stroke work index than group P. There were comparable decreases
      in mean arterial pressure on induction of anesthesia, 14% and 8% in group N and
      group P, respectively. In both groups, right ventricular ejection fraction was
      unchanged. CONCLUSIONS: The use of a propofol infusion for induction and
      maintenance of anesthesia in patients with low cardiac output states undergoing
      cardiac surgery is not contraindicated.

PMID- 7579103
TI  - Continuous infusions of alfentanil and propofol for coronary artery surgery.
AB  - OBJECTIVE: To study the anesthetic efficacy of two different background infusion
      rates for alfentanil in a total intravenous anesthesia (TIVA) technique using
      propofol. Therefore, the effects of these infusions on hemodynamic stability and
      on the suppression of hemodynamic and somatic responses to noxious stimuli were
      compared. DESIGN: Prospective and randomized. SETTING: The study was performed in
      a university hospital setting. Two patient groups were compared. INTERVENTIONS:
      Anesthesia was induced in group 1 (n = 16) with alfentanil 50 micrograms/kg and
      in group 2 (n = 14) with alfentanil 75 micrograms/kg, infused in 4 min, as well
      as with an infusion of propofol at a rate of 10 mg/kg/h in both groups. After 4
      min, the alfentanil infusion was reduced to 1 microgram/kg/min in group 1 and to
      2 micrograms/kg/min in group 2. The propofol infusion was reduced following
      sternal spread to 3 mg/kg/h. Responses indicating inadequate anesthesia were
      treated with additional alfentanil bolus doses. MEASUREMENTS AND MAIN RESULTS:
      Induction of anesthesia in group 1 was associated with significant decreases in
      systolic and diastolic (-13%) blood pressures, cardiac index (-16%) and left
      ventricular stroke work index (-31%). Hemodynamic changes were similar in group
      2, except for the greater fall in systemic vascular resistance during maintenance
      of anesthesia. There was no difference in the incidence of breakthrough
      hypertension between the two groups (in 44% and 43% of the patients,
      respectively) and in the number of alfentanil bolus supplements. There were also
      no differences in the incidence of ischemia, myocardial infarction or duration of
      postoperative ventilation. CONCLUSIONS: Because both infusions provided equally
      stable anesthesia, the lower infusion regimen for alfentanil is the more
      appropriate technique. Using this technique, the administration of additional
      alfentanil boluses just before stressful surgical episodes will further improve
      hemodynamic stability.

PMID- 7579105
TI  - Serum lipid and glucose concentrations with a propofol infusion for cardiac
      surgery.
AB  - OBJECTIVE: To document changes in serum lipids and glucose with a propofol
      infusion technique for cardiac surgery. DESIGN: Prospective cohort. SETTING:
      University teaching hospital. PARTICIPANTS: 22 elective cardiac surgical
      patients. INTERVENTIONS: Frequent venous blood sampling. MEASUREMENTS AND MAIN
      RESULTS: Serum lipids and glucose were measured at 10 time periods
      perioperatively, from preinduction until 4 hours post-cardiopulmonary bypass.
      Plasma propofol concentrations were also measured in 10 of these patients. There
      was a significant increase in glucose (P < 0.0005) and decreases in cholesterol
      (P < 0.0005), high-density lipoprotein (P = 0.004), and low-density lipoprotein
      (P < 0.0005); there was no significant change in triglycerides (P = 0.39). The
      propofol infusion resulted in acceptable plasma levels throughout the procedure
      and allowed early extubation in the intensive care unit, after a mean (SD) of
      7.14 (5.9) hours. There was a strong correlation between triglyceride and
      propofol levels at most time periods (r = 0.38 to 0.98). CONCLUSIONS: This study
      demonstrates that a propofol infusion technique does not result in elevation of
      serum lipids and supports its increased popularity in maintenance of anesthesia
      for cardiac surgery.

PMID- 7579106
TI  - Onset of segmental relaxation dysfunction with decreased myocardial tissue
      perfusion: modulation by propofol.
AB  - OBJECTIVES: To estimate myocardial oxygen needs by studying the effects of
      reduced coronary blood flow on segmental myocardial function. To study the
      tolerance of limited oxygen supply to a myocardial segment during propofol
      administration. DESIGN: A prospective experimental study. SETTING: An
      experimental animal laboratory in a university. PARTICIPANTS: Eighteen adult
      dogs, weighing 20 to 35 kg. INTERVENTIONS: Open thorax open pericardium
      experiments were performed under standard anesthetic conditions. Segment length
      gauges were placed subendocardially in an anteroapical and in a basal segment.
      Flow to the anteroapical segment was reduced by tightening a micrometer
      controlled snare placed around the second diagonal coronary artery. Left
      ventricular pressure-length signals allowed for identification of onset of
      relaxation dysfunction. Myocardial tissue flow at onset of relaxation dysfunction
      was defined as critical flow. Tracer microspheres were used to measure
      subepicardial, midwall, and subendocardial flow at critical flow. MEASUREMENTS
      AND MAIN RESULTS: Stability of the model and reproducibility of critical flow
      were studied in a first series of six dogs with the hearts paced at 110
      beats/min. Hemodynamics, left ventricular, and segmental myocardial function
      during critical flow were stable. Subendocardial critical flow was identical with
      each flow reduction (45% +/- 5, 44% +/- 8, and 43% +/- 5 of baseline myocardial
      tissue flow). In a second series of six dogs, critical flow was measured at
      pacing rates 100 beats/min, 150 beats/min, and 100 beats/min with propranolol,
      0.1 mg/kg, pretreatment. Critical flows were 38% +/- 5, 55% +/- 6, and 17% +/- 2
      of baseline, respectively (p < 0.05). In a third series of six dogs, critical
      flow was measured during sufentanil, 0.6 microgram/kg/min, and increasing doses
      of propofol (P0: 0.0 mg/kg/h, P4: 4.0 mg/kg/h and P8: 8.0 mg/kg/h). Heart rate
      was kept constant at 110 beats/min. When compared with P0, hemodynamic and left
      ventricular contraction parameters were stable at P4 but were decreased at P8. At
      P0, critical flow was: 0.63 +/- 0.14, at P4: 0.34 +/- 0.09, and at P8: 0.25 +/-
      0.07 mL/min/g (p < 0.05). CONCLUSION: Critical myocardial tissue flow was
      reproducible and sensitive for altered myocardial oxygen needs. The negative
      inotropic properties of P decreased myocardial oxygen needs during unchanged
      hemodynamic and left ventricular contraction parameters. A higher P dose
      depressed left ventricular function.

PMID- 7579107
TI  - Myocardial injury during reoperation for coronary artery bypass surgery.
AB  - OBJECTIVES: To determine the incidence, triggers, and timing of myocardial injury
      during reoperation for coronary artery bypass surgery. DESIGN: Prospective
      observational. SETTING: One tertiary care university hospital. PARTICIPANTS: 15
      patients undergoing reoperation. INTERVENTIONS: Multilead electrocardiographic
      monitoring approximately every 3 minutes during surgery. MEASUREMENTS AND MAIN
      RESULTS: The occurrence of a new ischemic ST elevation or depression on the
      electrocardiogram (ECG) was determined. A major deterioration in ventricular
      function after cardiopulmonary bypass (CPB) also was determined. Peak creatine
      kinase myocardial band (CK-MB) > or = 25 IU/L was considered to be the marker of
      myocardial injury. Seven patients demonstrated myocardial injury, all
      intraoperatively. Five of these patients had new ST elevation episodes before
      CPB. Three of the episodes were temporally associated with an abrupt increase in
      the heart rate. The other two episodes were temporally associated with surgical
      manipulation of the heart and the old grafts. The sixth patient had a significant
      deterioration of ventricular function during CPB. One of the patients who had ST
      elevation before CPB and the seventh patient developed ST elevation towards the
      end of protamine administration. CONCLUSIONS: In patients undergoing reoperation,
      the intraoperative incidence of myocardial injury, especially before CPB, was
      found to be substantially higher than that previously reported.

PMID- 7579109
TI  - Continuous thermodilution cardiac output: agreement with Fick and bolus
      thermodilution methods.
AB  - OBJECTIVE: Cardiac outputs were determined with continuous thermodilution, bolus
      thermodilution, and the Fick method during pharmacologically varied hemodynamics.
      DESIGN: Prospective comparison of techniques. SETTING: University animal
      laboratory. PARTICIPANTS: Swine. INTERVENTIONS: Swine were anesthetized,
      tracheally intubated, and instrumented to measure continuous (QTDC) and bolus
      (QTDB) thermodilution cardiac outputs and sample arterial and mixed venous blood.
      Continuous thermodilution of blood was facilitated by computer modulation of a
      thermal filament wrapped around the portion of the pulmonary artery catheter
      residing in the right atrium and ventricle. QTDC was computed from the
      thermodilution curve monitored by the thermistor. Bolus thermodilution was
      performed in triplicate by injecting 10 mL of 5% dextrose in water (0 to 4
      degrees C). Oxygen consumption (VO2) was calculated as the averaged minute rate
      of disappearance of spirometer oxygen over a 6-minute steady state. Cardiac
      output was determined with the direct Fick method (QF) by dividing VO2 by the
      difference in arterial and mixed venous oxygen content. Basal QTDC was increased
      and decreased with an intravenous infusion of dobutamine or labetalol,
      respectively. Data are summarized as mean +/- SD or 95% confidence interval (CI
      95%). Agreement between methods of determining cardiac output was assessed by
      calculating bias, percent bias, and percent coefficient of determination (100
      r2). MEASUREMENTS AND MAIN RESULTS: Eighteen swine (38.9 +/- 1.2 kg) exhibited a
      range of QTDC from 2.2 to 14.8 L/min. Mean measurement variance of VO2, CaO2,
      CvO2, and QTDB was 1.5%, 1.5%, 2.0%, and 11.8%, respectively. Mean bias, percent
      bias, and 100 r2 was 0.004 +/- 1.05 L/min (CI 95%: 0.18 to 0.19 L/min), -0.37 +/-
      13.8% (CI 95%: -2.75 to 2.01), and 89% between QTDC and QF, respectively. Bias,
      percent bias, and 100 r2 was 0.05 +/- 1.09 L/min (CI 95%: -0.14 to 0.23 L/min,
      1.21 +/- 13.06% (CI 95%: -1.03 to 3.46%), and 91% between QTDC and QTDB,
      respectively. Bias, percent bias, and 100 r2 (Fig 6) was -0.04 +/- 0.69 L/min (CI
      95%: -0.16 to -.08 L/min), -1.23 +/- 9.17% (CI 95%: -2.8 to 0.35%), and 94%
      between QTDB and QF, respectively. CONCLUSION: Automatic cardiac output computed
      with continuous thermodilution appears accurate and reliable. Also, good
      agreement was confirmed between cardiac output derived by continuous and bolus
      thermodilution methods and bolus thermodilution and Fick methods.

PMID- 7579108
TI  - Systemic gaseous microemboli during left atrial catheterization: a common
      occurrence?
AB  - OBJECTIVE: Gaseous microemboli during cardiac surgery have been implicated as a
      potential cause of postoperative neurologic injury. Any monitoring technique that
      exposes the systemic circulation to atmospheric pressure could introduce gaseous
      microemboli, causing cerebral microembolization. The incidence of carotid artery
      gaseous microemboli was studied during left atrial catheter insertion. DESIGN:
      Prospective clinical study. SETTING: Tertiary care university hospital.
      PARTICIPANTS: Twelve patients undergoing elective cardiac surgery. INTERVENTIONS:
      Perioperatively, a 5-MHz continuous wave Doppler probe was positioned over the
      left carotid artery to maximally record blood flow signals. The criteria used for
      detecting a gaseous microembolus were a sudden increase in the amplitude of the
      visual signal by 30% and a characteristic audible sound. MEASUREMENTS AND MAIN
      RESULTS: Numbers of microemboli at three timepoints (before and during left
      atrial catheter insertion and during catheter flushing) were assessed using the
      Friedman test. No emboli were detected before left atrial catheter insertion.
      When compared with the preinsertion time period, statistically (p < 0.05)
      significant numbers of gaseous microemboli were found in six patients during
      catheter insertion (3 +/- 1 microemboli; range 1 to 7 microemboli) and in five
      patients during catheter flushing (5 +/- 2 microemboli; range 1 to 12
      microemboli). There was a tendency for patients with lower filling pressures to
      entrain more microemboli during insertion (r = 0.44; p = 0.149). No patient
      showed evidence of gross neurologic dysfunction postoperatively, although
      sensitive neurologic testing was not performed. CONCLUSIONS: Left atrial catheter
      insertion and flushing can cause systemic gaseous microemboli in more than 50% of
      patients. Although the number of microemboli introduced is relatively small,
      extreme care should be used during left atrial catheter insertion.

PMID- 7579110
TI  - Continuous versus intermittent cardiac output measurement in cardiac surgical
      patients undergoing hypothermic cardiopulmonary bypass.
AB  - OBJECTIVE: Continuous thermodilution cardiac output (CCO) measurement was
      clinically evaluated in patients who underwent coronary revascularization using
      hypothermic low-flow, low-pressure cardiopulmonary bypass (CPB). DESIGN:
      Prospective study. SETTING: University hospital setting. PARTICIPANTS: 30 cardiac
      surgical patients. INTERVENTIONS: CCO was correlated to standard bolus
      thermodilution cardiac output (ICO) obtained at end-expiration. MEASUREMENTS AND
      MAIN RESULTS: Measurements were taken at selected time points (n = 18) before
      anesthesia induction, before CPB, and 5 minutes to 12 hours after CPB. A total of
      540 data pairs were thus obtained. ICO ranged from 1.9 to 9.9 L/min, CCO from 1.5
      to 9.9 L/min. Correlation between ICO and CCO was highly significant (r = 0.872;
      p < 0.01), accompanied by an excellent accuracy (bias -0.0213 L) and precision
      (0.59 L) before CPB and more than 45 minutes after CPB. However, during the first
      45 minutes after CPB, there was no correlation (r = 0.273) between ICO and CCO,
      and ICO tended to be relatively high, whereas CCO measurements showed relatively
      low values. During the first 45 minutes after hypothermic CPB, but not during the
      ensuing time period, central blood temperature decreased, which may be
      interpreted as a lack of thermal equilibration between central and peripheral
      compartments. It is hypothesized that thermal instability in combination with
      increased respiratory variations in pulmonary artery blood temperature caused
      inhomogenous rewarming of different body sites and might be the main reason for
      the lack of correlation between ICO and CCO. CONCLUSIONS: Despite an excellent
      correlation, accuracy, and precision between CCO and ICO before CPB and more than
      45 minutes after hypothermic CPB, a lack of correlation in the early phase after
      CPB has been found. Further investigation is needed to elucidate the underlying
      cause of these findings and to clarify whether ICO or CCO or both fail to
      represent the real cardiac output up to 45 minutes after weaning from hypothermic
      CPB.

PMID- 7579111
TI  - Evaluation of the Paratrend 7 intravascular blood gas monitor during cardiac
      surgery: comparison with the C4000 in-line blood gas monitor during
      cardiopulmonary bypass.
AB  - OBJECTIVE: To evaluate the performance of the Paratrend 7 intravascular blood gas
      monitor (Biomedical Sensors, High Wycombe, UK, Ltd) during cardiac surgery and
      compare it with that of an in-line blood gas monitor placed in the arterial limb
      of an extracorporeal circuit during cardiopulmonary bypass. DESIGN: A prospective
      study. Consecutive patient enrolment. SETTING: In the cardiac surgical intensive
      care units at a tertiary referral center. INTERVENTION: Insertion of the
      Paratrend 7 intravascular sensor through the radial arterial catheter after
      induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Simultaneous measurements
      of pH, PCO2, and PO2 were made from the sensor and the blood gas analyzer, and
      the bias and precision were calculated on all the measured parameters. The bias
      and precision of the intravascular sensor during bypass for pH, PCO2, and PO2
      were 0.01 and 0.06 pH units, 0.5 and 2.5 mmHg (2% and 8%), and 3 and 45 torr
      (0.5% and 14%), respectively. The bias and precision for the prebypass and the
      postbypass phases were comparable. The bias and precision of the extracorporeal
      monitor for pH, PCO2, and PO2 were 0.04 and 0.1 pH units, -0.3 and 4 mmHg (-1%
      and 15%) and 8 and 48 mmHg (4 and 18%), respectively. There were no instances of
      any complications attributable to the intravascular sensor. CONCLUSIONS: The
      intravascular sensor used in this study functioned well during cardiopulmonary
      bypass and the postbypass phase. The performance of the intravascular sensor was
      better than the in-line blood gas monitor during cardiopulmonary bypass.

PMID- 7579113
TI  - Incidence and management of large-bore introducer sheath puncture of the carotid
      artery.

PMID- 7579112
TI  - Cardiopulmonary bypass for adult patients: a survey of equipment and techniques.
AB  - OBJECTIVES: The techniques and equipment used for cardiopulmonary bypass for
      adult cardiac surgery vary among institutions and may change over time. This
      study sought to document the changing patterns of practice. DESIGN: Voluntary
      survey of meeting participants. SETTING: 13th Annual San Diego Cardiothoracic
      Surgery Symposium (February 1993). PARTICIPANTS: There were 331 responses from
      perfusionists (79.5%), cardiac surgeons (11.2%), and anesthesiologists (6.3%).
      The majority of these participants were from institutions where more than 1,000
      cardiac operations were performed annually. MEASUREMENTS AND MAIN RESULTS: It was
      found that 91.5% of the respondents used membrane oxygenators currently, compared
      with 5% in 1982 (as reported in a previous survey). Over 80% of the institutions
      surveyed used some type of perioperative cell-salvaging technique. Arterial line
      filters were used by 92% of the respondents compared with 64% in 1982. Also, 80%
      of the respondents were aware of the availability of leukocyte-depleting filters.
      CONCLUSIONS: The probable reasons for the increased utilization of membrane
      oxygenators and arterial line filters include less damage to the formed elements
      of blood, fewer gaseous microemboli, and better control of carbon dioxide
      elimination and oxygenation. The authors anticipate that future surveys will
      document increased use of leukocyte-depleting filters because of the literature
      implicating neutrophils as mediators of tissue destruction in various disease
      processes, including myocardial reperfusion injury.

PMID- 7579114
TI  - Avulsion of the right facial vein during double cannulation of the internal
      jugular vein.

PMID- 7579116
TI  - Clinical value of aortic thermodilution monitoring of cardiac output in a small
      child after surgical correction of tetralogy of Fallot.

PMID- 7579115
TI  - Loss of a right radial arterial pressure tracing during thoracic aortic aneurysm
      repair.

PMID- 7579118
TI  - Perioperative fluid management for thoracic surgery: the puzzle of
      postpneumonectomy pulmonary edema.

PMID- 7579117
TI  - Transesophageal echocardiographic diagnosis of sinus venosus-type atrial septal
      defect associated with partial anomalous venous connections during cardiac
      surgery in adults.

PMID- 7579119
TI  - Case 4--1995. Perioperative myocardial infarction in a patient undergoing
      abdominal aortic aneurysm resection: perioperative risk assessment.

PMID- 7579120
TI  - Pro: early extubation after cardiac surgery decreases intensive care unit stay
      and cost.
AB  - The recurrent or new trends of early extubation after cardiac surgery are here to
      stay in the 1990s. The preoperative status does not necessarily predict the
      postoperative course and prolonged mechanical ventilation following cardiac
      surgery should not be uncritically considered as routine. All patients should be
      assessed for tracheal extubation at the earliest opportunity when the criteria
      are met in the ICU. Early extubation post-cardiac surgery does reduce ICU and
      hospital length of stay and costs. It also allows early ICU discharge and reduces
      case cancellations without any increase in postoperative complications and
      readmission. These studies have emphasized that the change in the process of care
      to early extubation can affect patient outcome as well as costs in cardiac
      patient care. The substantial difference in cost savings per cardiac case between
      "criteria discharge" and "actual discharge" points out the importance of the
      organization of the process of care being delivered. To achieve maximum cost
      benefit from early extubation in cardiac patients, the organization of the
      perioperative management of these patients must be optimized. This process of
      care includes intraoperative anesthetic modification; organization of ICU and
      staff expertise; postoperative early extubation and management; acute pain
      service; ICU discharge policy; utilization of step-down unit and surgical ward;
      and communication among cardiac patient management teams (cardiovascular surgeon,
      cardiac anesthesiologist, ICU staff, nurses, respiratory therapists,
      physiotherapists, and social workers), which are all vital to the success of such
      a program.

PMID- 7579121
TI  - Con: early extubation after cardiac surgery does not decrease intensive care unit
      stay and cost.

PMID- 7579122
TI  - Hypotension on initiation of cardiopulmonary bypass.

PMID- 7579124
TI  - Primary pulmonary sarcoma presenting as an atrial myxoma: intraoperative
      transesophageal echocardiographic evaluation.

PMID- 7579123
TI  - Anaphylactic reaction to aprotinin.

PMID- 7579126
TI  - Pulmonary artery catheter misplaced in liver.

PMID- 7579125
TI  - Hydrocortisone pretreatment for attenuation of protamine-induced adverse
      hemodynamic reactions.

PMID- 7579127
TI  - Cardiac Troponin-T and perioperative myocardial damage in coronary surgery.

PMID- 7579128
TI  - Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of
      migraine.
AB  - In primates, histamine activates cerebral endothelial H1-receptors leading to
      formation of nitric oxide (NO). Twenty migraine patients received pretreatment
      with placebo or the histamine-H1-receptor antagonist, mepyramine, in a
      randomized, double blind fashion, followed in both groups by i.v. histamine (0.5
      microgram kg-1 min-1 for 20 min). Headache characteristics were subsequently
      observed for 12 h. In patients given placebo histamine caused immediate headache
      during the infusion followed by a delayed migraine attack fulfilling IHS criteria
      for migraine without aura. The temporal profile of induced headache was exactly
      the same as after glyceryl trinitrate. Mepyramine pretreatment abolished both
      immediate headache and delayed migraine attacks. Our results suggest that a
      migraine attack can be caused by NO formation in the endothelium of cerebral
      arteries.

PMID- 7579129
TI  - Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine.
      Relevance to Parkinson's disease.
AB  - The mechanism of nigral cell death in Parkinson's disease (PD) remains unknown,
      but it is increasingly proposed that free radical reactions are important in the
      disease pathology. One of the most striking features of PD is an approximate 40%
      decrease in the levels of reduced glutathione (GSH) which occurs early in the
      development of the disease. We describe a possible mechanism of GSH depletion
      which results from the reaction of L-DOPA and dopamine with the superoxide free
      radical (O2.-) and leads to a very rapid loss of GSH.

PMID- 7579130
TI  - Gender differences in cerebral ascorbate levels and ascorbate loss in ischemia.
AB  - Ascorbate and glutathione (GSH) are the primary water-soluble antioxidants in the
      CNS. Oxidative stress, sometimes indicated by loss of these antioxidants, has
      been linked to several clinical and experimental conditions, including cerebral
      ischemia. These conditions are also gender-linked, with greater incidence or
      severity in males than females. To test whether there are gender differences in
      oxidant/antioxidant regulation, we determined basal levels of ascorbate and GSH
      in rat brain and their loss after 1 h decapitation ischemia. We found that
      ascorbate levels in male rat brain were 7-10% higher than in females, depending
      on region, whereas GSH levels were gender-independent. Significant ascorbate loss
      (up to 12%) occurred in males during ischemia, with a regional pattern of
      cerebellum > hippocampus > prefrontal cortex. Loss of ascorbate in females was
      not significant in any region. By contrast, loss of GSH was significant in both
      males and females. Greater loss of GSH than ascorbate was in agreement with
      previous studies and was consistent with loss from enzymatic degradation, as well
      as oxidation. The significant gender difference in ascorbate loss, as a marker of
      oxidative stress, supports the hypothesis that inherent differences in
      oxidant/antioxidant regulation contribute to gender differences in response to
      ischemia and other pathological conditions.

PMID- 7579131
TI  - Effects of intravenously infused pituitary adenylate cyclase-activating
      polypeptide on arginine vasopressin and oxytocin secretion in man.
AB  - In order to establish possible stimulatory effects of increasing plasma
      concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) on
      arginine vasopressin (AVP) and/or oxytocin (OT) secretion, successively
      increasing doses of PACAP-38 (2, 4 and 8 pmol kg min-1; each dose for 20 min)
      were infused in seven normal men. Plasma AVP and OT levels were measured before
      infusion and every 20 min, just before increasing the infusion dose of PACAP.
      During tests, PACAP infusion did not produce untoward side effects or changes in
      blood osmolality and/or pressure. Plasma OT levels did not change during PACAP
      infusion. Plasma AVP concentrations were not modified by infusion of the lowest
      dose of PACAP, whereas they were significantly increased in a dose-response
      fashion when higher amounts of PACAP were given. These findings demonstrate for
      the first time in humans that the systemic administration of PACAP exerts
      stimulatory effects on AVP, but not OT secretion.

PMID- 7579132
TI  - Selective disruption of eyeblink classical conditioning by concurrent tapping.
AB  - A total of 140 normal adults participated in one of seven conditions designed to
      test the hypothesis that memory systems may be distinguished on the basis of
      their neurobiological substrates. The results revealed a selective disruption of
      eyeblink classical conditioning (EBCC) when it was performed concurrently with
      tapping, another cerebellar task. Subjects simultaneously engaged in EBCC and a
      recognition task or control tasks were relatively unimpaired in EBCC. Results
      provide evidence for the existence of neurobiologically distinct memory systems,
      and suggest that the selective disruption of EBCC, when concurrently performed
      with tapping, may be attributed to cerebellar involvement in both tasks.

PMID- 7579133
TI  - Role of hippocampal NO in the acquisition and consolidation of inhibitory
      avoidance learning.
AB  - Nitric oxide (NO), an unconventional neurotransmitter in the brain, has been
      postulated as a retrograde intercellular messenger necessary for the induction,
      but not the maintenance phase, of activity-dependent forms of synaptic plasticity
      in the hippocampus. Here we report on the effects of an inhibitory avoidance
      learning task on hippocampal NO synthase (NOS) activity and on the effects of
      intrahippocampal infusion of a NOS inhibitor in the acquisition and consolidation
      of this task in rats. NOS activity increases by 45% in the hippocampus
      immediately after training (0 min) but not at 60 min after training. No changes
      were observed in cerebellar NOS activity. The bilateral intrahippocampal
      microinjection of nitro-arginine (NO-arg), an NOS inhibitor, provoked retrograde
      amnesia for the inhibitory avoidance when given 10 min before or immediately
      after training, but not 60 min after training. These results suggest that NO
      regulated processes in the hippocampus play an important role at the time of
      training or very shortly thereafter of an inhibitory avoidance learning.

PMID- 7579134
TI  - Noradrenaline and potentiation in the chick brain slice.
AB  - The role of the noradrenergic system as a modulator of neurotransmission in the
      chick forebrain was investigated in brain slices containing the medial
      hyperstriatum ventrale, an area known to be involved in learning and memory. The
      alpha 2-agonist clonidine (20 microM) decreased the post-synaptic response to
      local stimulation at 0.1 Hz, while activation of beta 2 receptors increased this
      response. Induction of persistent potentiation following stimulation at 5 Hz was
      blocked by drugs (20 microM ICI 118,551; 20 microM propranolol) which showed
      preferential antagonistic activity at the beta 2 receptor but not by the beta 1
      preferential antagonist timolol. This effect may be due to an interaction with
      the NMDA receptor system.

PMID- 7579135
TI  - Synergistic effect of intrastriatal co-administration of L-NAME and quinolinic
      acid.
AB  - Chronic dialytic intrastriatal co-administration of quinolinic acid (QUIN) and
      four concentrations of the nitric oxide synthase (NOS) inhibitor NG nitro-L
      arginine methyl ester (L-NAME) produced variable results. Low concentrations of L
      NAME (1 microM and 50 microM) co-administered with 15 mM QUIN produced lesions
      not significantly different from those produced by 15 mM QUIN alone. In contrast,
      higher concentrations of L-NAME (1 mM and 100 mM) co-administered with 15 mM QUIN
      produced striatal lesions significantly larger than those produced by 15 mM QUIN
      alone. Administered by itself, 100 mM L-NAME produced little striatal damage.
      These findings suggest that low levels of NOS inhibition have little or no effect
      on NMDA neurotoxicity in the striatum, whereas high levels of NOS inhibition
      increase NMDA-induced striatal lesion volume.

PMID- 7579136
TI  - Cognitive functioning in experimental hypoglycaemia assessed with event-related
      potentials.
AB  - Cognitive effects of experimentally induced hypoglycaemia were investigated by
      event-related brain potentials (ERPs) in auditory and visual classification
      tasks. In a cross-over design eight healthy male subjects (age 22-27 years) were
      studied under control conditions or following administration of 0.15 IU insulin
      kg-1. The ERPs showed preserved early cortical components, while the N2 component
      was greatly reduced in both modalities. P3 components did not show an influence
      of hypoglycemia. These results suggest that the cognitive deficits are due to an
      impairment of automatic feature extraction from the stimuli.

PMID- 7579137
TI  - ApoE genotypes in Australia: roles in early and late onset Alzheimer's disease
      and Down's syndrome.
AB  - We studied the apoE genotypes of 279 Australians in order to determine what
      relationships might exist in this group between apoE genotype and dementia
      associated with either early- or late-onset sporadic Alzheimer's disease (AD) or
      with Down's syndrome (DS). ApoE epsilon 4 allele frequency was increased in
      Australians with either early-onset sporadic AD (p < 0.002) or late-onset
      sporadic AD (p < 0.0001) and apoE epsilon 2 allele frequency was decreased in the
      late-onset sporadic AD group (p < 0.01). The apoE genotype distribution among
      patients with DS was not different from that of the control group. One individual
      with DS and an apoE epsilon 4/epsilon 4 genotype developed dementia at the
      earliest age of dementing DS patients, consistent with a role for apoE epsilon 4
      in determining age of onset of dementia in AD and DS. Another DS patient with an
      apoE epsilon 2/epsilon 3 genotype developed dementia within an age range similar
      to that of four demented DS patients with an apoE epsilon 3/epsilon 3 genotype,
      an observation which would appear inconsistent with the proposed protective
      effect of apoE epsilon 2 to delay onset of dementia in DS. These results extend
      the evidence that the apoE genotype, particularly apoE epsilon 4, modulates
      dementia in early- and late-onset sporadic AD and DS. The protective role of apoE
      epsilon 2 in DS, however, may vary among different populations or ethnic groups.

PMID- 7579138
TI  - Repulsive and attractive mechanisms for the formation of corticofugal
      projections.
AB  - Neocortical neurones project axons to subcortical and cortical structures
      according to their laminar location. The axon-target interactions which produce
      lamina-specific efferent connections were studied in an organotypic coculture of
      rat visual cortex with either superior colliculus (SC) or heat-treated SC.
      Morphological studies with fluorescent dye demonstrated that axons from upper
      layer neurones did not invade living SC, which receives axonal projections from
      layer 5, but did extend into denatured SC. In addition, the treatment
      considerably reduced the number of layer 5 neurones which project to the SC.
      These results suggest that SC contains a repulsive factor for axonal extension
      from the upper cortical layer as well as an attractive factor for axonal growth
      from layer 5 neurones.

PMID- 7579139
TI  - Altered distribution of cholinergic cells in the narcoleptic dog.
AB  - Narcolepsy is characterized by excessive sleepiness and episodes of cataplexy
      brought on by emotional excitation. Cataplexy and sleep paralysis have been
      hypothesized to be produced by the triggering during waking of brain stem
      cholinergic mechanisms normally acting to induce atonia in REM sleep. We
      hypothesized that narcoleptics have an abnormal number of LDT and/or PPN
      cholinergic neurons. A comparison was made of cholinergic cell numbers in the
      brain stems of normal and narcoleptic canines. Cholinergic neurons were
      identified by NADPH-diaphorase histochemistry. We found increased numbers of
      cholinergic neurons at the R6-R7 level of the LDT and PPN in narcoleptic canines.
      This abnormality can explain alterations in cholinergic receptor number,
      acetylcholine release, and the occurrence of cataplexy and sleep paralysis that
      characterize narcolepsy.

PMID- 7579140
TI  - Nitric oxide synthase inhibition decreases pontine acetylcholine release.
AB  - This study tested the hypothesis that inhibition of nitric oxide synthase (NOS)
      in the medial pontine reticular formation (mPRF) would cause decreased
      acetylcholine (ACh) release. Microdialysis of cat mPRF permitted measurement of
      ACh during states of wakefulness, non-rapid eye movement (NREM) sleep and rapid
      eye movement (REM) sleep. ACh release during microdialysis with Ringers (control)
      was compared to ACh release during microdialysis with 10 mM NG-nitro-L-arginine
      (NLA). The NOS inhibitor NLA caused a significant reduction in ACh released from
      the mPRF during wakefulness, NREM sleep, and REM sleep. This reduction in mPRF
      ACh release elicited by NLA suggests that nitric oxide (NO) contributes to
      cholinergic neurotransmission in the pontine reticular formation.

PMID- 7579141
TI  - Parallel suppression of retinal and pineal melatonin synthesis by retinally
      mediated light.
AB  - We have recently shown that light, over a narrow range of low intensities
      suppresses the activity of the enkephalin-immunoreactive amacrine cells of the
      chicken retina. In this paper, we show that over the same range of low light
      intensities the rate of melatonin synthesis in both the retina and the pineal of
      the chicken is suppressed. We further show that the effects of light on the
      pineal at these low intensities are mediated by the retina and not by direct
      actions on the pineal. Combined with our evidence that dopaminergic pathways
      within the retina are involved in controlling the state of activity of the
      pineal, these results suggest, but do not prove, that the change in state of a
      microcircuit within the retina involving the photoreceptors, dopaminergic
      amacrine cells and enkephalin-immunoreactive amacrine cells may be causally
      related to changes in the state of the pineal.

PMID- 7579143
TI  - P2y purinergic receptors coupled to phosphoinositide hydrolysis in tissues of the
      cochlear lateral wall.
AB  - The tissues of the lateral wall of the cochlea, spiral ligament and stria
      vascularis, maintain homeostasis of the inner ear through the production of
      endolymph and regulation of cochlear blood flow. We examined the effects of
      purinergic agonists on the release of inositol phosphates (InsPs) in intact
      isolated lateral wall tissues of the Fischer-344 rat. After preincubation with
      myo[3H]inositol, stimulation with the P2 purinergic agonist ATP-gamma-S resulted
      in a concentration-dependent increase in the formation of [3H]InsPs. The P2
      purinergic agonist alpha,beta-methylene ATP (AMP-CPP) was a weaker stimulant, and
      the P1 purinergic agonist adenosine was ineffective. These results are consistent
      with the presence of P2y receptors and a purinergically controlled InsP3 second
      messenger system in the cochlear lateral wall.

PMID- 7579142
TI  - NT-3 combined with CNTF promotes survival of neurons in modiolus-spiral ganglion
      explants.
AB  - Auditory neurons depend upon the integrity of both their peripheral (auditory
      hair cells) and central (cochlear nucleus) targets for survival. One proposed
      trophic mechanism is the production of neurotrophin-3 (NT-3) by auditory hair
      cells. Modiolus-spiral ganglion explants from adult rats that closely mirror cell
      cell interactions and in vivo tissue relationships within this ganglion provide a
      model for testing trophic factors. Brain derived neurotrophic factor (BDNF), NT-3
      and ciliary neurotrophic factor (CNTF) were tested for their ability, both
      individually and in combination, to support neuronal survival. NT-3 was the
      strongest individual promoter of survival, while CNTF (a cytokine) with NT-3 (a
      neurotrophin) was the most effective combination for promoting the survival of
      auditory neurons.

PMID- 7579144
TI  - The neuroprotective effect of a potent and selective inhibitor of type I NOS (L
      MIN) in a rat model of focal cerebral ischaemia.
AB  - Our newly synthesized delta-(S-methylisothioureido)-L-norvaline (L-MIN) was shown
      to have potent inhibitory effects on Ca(2+)-dependent and constitutively
      expressed neuronal nitric oxide synthase (type I NOS) when compared to other
      commonly recognized NOS inhibitors and produced an IC50 value of 5.7 nM. By
      contrast, this compound exhibited more than 40-fold weaker inhibitory effects on
      the other NOS isoforms. Administration of L-MIN (0.1, 0.3 and 1 mg kg-1, i.p.) to
      rats immediately after 2 h middle cerebral artery occlusion and 2 h reperfusion
      reduced infarct size in a dose-dependent manner. These results suggest that type
      I NOS activation has a crucial role in the pathogenic cellular mechanisms
      underlying cerebral ischaemia.

PMID- 7579146
TI  - Benzodiazepine antagonist flumazenil reduces hippocampal epileptiform activity.
AB  - We examined the effects of the benzodiazepine antagonist, flumazenil, on
      epileptiform discharges evoked in the hippocampal CA1 region in vitro.
      Application of 100 nM flumazenil did not affect normal synaptic responses;
      however, flumazenil did depress epileptiform discharges induced by 8 mM [K+]o.
      Epileptiform discharges induced by the GABAA channel antagonist picrotoxin or by
      the K+ channel blocker 4-aminopyridine were unaffected. Application of the high
      affinity, low-efficacy benzodiazepine partial inverse agonist, Ro 19-4603,
      blocked the anticonvulsant effect of flumazenil, indicating that this action of
      flumazenil is mediated at a benzodiazepine binding site located on the GABAA
      receptor. A likely explanation of the present results is that flumazenil
      antagonizes the action of an endogenous benzodiazepine inverse agonist, which is
      released during epileptiform discharges evoked in high K+ ACSF.

PMID- 7579145
TI  - Evidence of a central antinociceptive effect of paracetamol involving spinal 5HT3
      receptors.
AB  - This study was carried out to determine both the effect of systemic paracetamol
      on the C-fibre evoked reflex activity, a test sensitive to centrally acting
      analgesic drugs, and the influence of an intrathecally administered 5HT3 receptor
      antagonist, tropisetron. Paracetamol (200, 300, 400 mg kg-1, i.v.) dose
      dependently decreased (maximal effects -60 +/- 8%) the C-evoked responses for a
      duration of 90 min (for the lowest dose). This effect was totally suppressed by
      tropisetron (1 microgram, i.t.). These data confirm previous studies suggesting a
      central effect of this drug and demonstrate the involvement of a spinal 5HT3
      mediated serotonergic mechanism.

PMID- 7579148
TI  - Dendritic spines form 'collars' in hippocampal granule cells.
AB  - A quantitative study of the distribution of dendritic spines was carried out in
      three orders of dendritic branches of granule cells from the dentate gyrus of the
      rat hippocampus. Golgi-stained preparations (7-19 neurones in each of seven rats)
      were analysed using computerized microscopy. Identification of spines and
      quantification of stem-spine geometry was performed using a segmentation
      algorithm and a line skeleton transformation of dendritic images. Analysis of
      data using the statistics of point processes revealed that, in all three branch
      orders, the distribution of visible spines along dendrites was not evenly random,
      but included dense clusters of spines surrounding the dendritic stem (spine
      'collars'). Three-dimensional reconstructions from serial ultrathin sections have
      confirmed the presence of such spine groups. We speculate the spine collars
      represent a functional element in which associative synaptic plasticity is
      fostered by the proximity of individual synapses.

PMID- 7579147
TI  - Acetylcholine modulates ganglion cell activity in the trout pineal organ.
AB  - In the teleost pineal organ light activates functional photoreceptors, which
      transmit electrical activity to the brain via axons of intermediate ganglion
      cells. To investigate whether acetylcholine plays a role in the transduction of
      pineal photoreceptor signals, extracellular recordings were performed from
      ganglion cells of intact superfused pineal organs of the rainbow trout. Bath
      applied acetylcholine increased the spike discharge rate of 96% of achromatic
      ganglion cells in a dose-dependent manner. The light response curve of ganglion
      cells, which was obtained by plotting spike rate vs light intensity, was
      significantly shifted by acetylcholine to higher frequencies. Acetylcholine was
      also active if applied during synaptic blockade with low Ca2+/high Mg(2+)-medium,
      demonstrating the presence of cholinergic receptors at the ganglion cell level.
      These data represent the first demonstration of acetylcholine constituting a
      postsynaptic modulation of photoreceptor signals in the trout pineal organ.

PMID- 7579149
TI  - Zinc reduces dentate granule cell hyperexcitability in epileptic humans.
AB  - The hippocampi of epileptic patients with medial temporal lobe epilepsy exhibit a
      characteristic pattern of anatomical changes including cell loss and sprouting of
      the granule cell axons, the mossy fibers, into the inner molecular layer of the
      dentate. In addition to glutamate, mossy fibers release Zn2+. In the present
      study we investigated the action of Zn2+ on excitatory synaptic potentials in the
      dentate granule cells of patients with medial temporal lobe epilepsy. We show
      here that Zn2+ limits the duration of excitatory responses in these cells,
      probably by blocking the N-methyl-D-aspartate (NMDA) receptors. Zinc may,
      therefore, play an important role in limiting epileptiform activity in this
      issue.

PMID- 7579150
TI  - Expression of the neurofibromatosis 1 (NF1) gene in reactive astrocytes in vitro.
AB  - Neurofibromin, the product of the neurofibromatosis 1 (NF1) gene, is an important
      tumor suppressor protein expressed most abundantly in the nervous system. Within
      the central nervous system, neurofibromin has been localized to neurons and
      oligodendrocytes but not astrocytes. As individuals with NF1 are at an increased
      risk for optic pathway gliomas and astrocytomas, we chose to re-evaluate the
      level of neurofibromin expression in primary cultures of murine cortical
      astrocytes under control and reactive conditions. Astrocytes under control
      conditions expressed low levels of NF1 mRNA and protein. Following stimulation
      with dibutyryl-cyclic AMP or interferon-gamma in combination with either
      lipopolysaccharide or interleukin-1 beta, there was a marked increase in NF1 mRNA
      and protein expression. These results suggest that neurofibromin may be involved
      in the process of reactive astrocytosis seen in response to CNS injury.

PMID- 7579152
TI  - Dual brain stem projection from the cortical masticatory area in guinea-pig.
AB  - The cortical masticatory area (CMA) in the guinea pig is subdivided into the
      anterior and posterior parts (A-CMA and P-CMA), based on the pattern of the CMA
      induced rhythmical digastric EMG burst and the cytoarchitecture. The anterograde
      tracing of horseradish peroxidase from the A-CMA and P-CMA revealed, in addition
      to a common projection to the region around the trigeminal motor nucleus and the
      parvicellular reticular formation bilaterally, a massive projection to the
      ipsilateral superior colliculus (SC) from the A-CMA but not from the P-CMA. The
      results suggest a dual brain stem projection system from the CMA: the direct
      pyramidal route from the P-CMA and the SC-mediated indirect route from the A-CMA.

PMID- 7579151
TI  - A single point mutation decreases picrotoxinin sensitivity of the human GABA
      receptor rho 1 subunit.
AB  - The GABA receptor rho subunits are thought to form bicuculline-insensitive and
      picrotoxinin-sensitive GABAC receptors. We have investigated the role of the
      amino acid at position 309 in transmembrane segment M2 of the human rho 1 subunit
      as a determinant for picrotoxinin sensitivity. The mutant rho 1P309S was
      constructed by exchanging proline 309 for serine, the corresponding amino acid of
      the human rho 2 subunit. Whole-cell recordings from HEK-293 cells transfected
      with rho 1P309S cDNA revealed that the sensitivity of the rho 1P309S channels for
      picrotoxinin was four-fold lower than that of the wild type rho 1 subunit. The
      affinity of the mutant receptor for GABA was only slightly changed. These results
      provide direct evidence that the amino acid at position 309 is an important
      determinant for the picrotoxinin sensitivity of GABA receptors formed by the rho
      subunits.

PMID- 7579153
TI  - Nicotinic acetylcholine receptors on capsaicin-sensitive nerves.
AB  - To study the density of nicotinic acetylcholine receptors on primary afferents
      and central nociceptive pathways, [3H](-)-nicotine binding was conducted in the
      cerebral cortex and spinal cord including dorsal roots and ganglia (DRG), of
      control rats and rats desensitized by neonatal capsaicin treatment. [3H](-)
      nicotine binding in capsaicin-treated rats was reduced in cerebral cortex by 35%
      and spinal cord+DRG by 46% (p < 0.05). Functionally, both iontophoretically
      applied acetylcholine- and capsaicin-evoked flares (measured by laser Doppler
      flowmetry) were reduced in capsaicin-treated animals (p < 0.05); similarly,
      electrical stimulation-evoked flares were significantly lower in the same group,
      compared with controls (p < 0.05). These data provide direct evidence that many
      neuronal nicotinic acetylcholine receptors are associated with capsaicin
      sensitive peptidergic neurones, including primary afferents, DRG and central
      nociceptive pathways.

PMID- 7579154
TI  - Modification of A1 and A2a adenosine receptor binding in aged striatum,
      hippocampus and cortex of the rat.
AB  - Age-related changes of A1 and A2a adenosine receptor binding characteristics were
      investigated in three regions of the rat brain using the A1 selective antagonist
      [3H]DPCPX, and the A2a selective agonist [3H]CGS 21680. The density of A1 binding
      sites in aged rats (24 months) was decreased by 33% in the hippocampus and by 60%
      in the cortex and was unchanged in the striatum when compared with young adult
      rats (6 weeks), with no change in KD. There were also age-related changes in the
      density of A2a binding sites: in the cortex, there was a 94% increase in the
      number of [3H]CGS 21680 binding sites in aged rats compared with young rats, and
      a similar tendency was observed in the hippocampus (32% increase in A2a binding
      sites in aged rats), with no change in KD; in the striatum there was a tendency
      for a decrease (22%) in the number of [3H]CGS 21680 binding sites in aged rats,
      and a decrease in KD. These results suggest that there are age-related changes in
      the balance between inhibitory A1- and excitatory A2a-adenosine receptor-mediated
      actions, which vary in different brain areas: in the cortex and hippocampus, the
      balance might be shifted towards adenosine-mediated excitatory actions, since
      there is an increase in the number of A2a receptors and a decrease in the number
      of A1 receptors upon ageing. In contrast, in the striatum, the A1/A2a ratio might
      be only slightly affected upon ageing.

PMID- 7579155
TI  - Phenotypic alterations of petal and sepal by ectopic expression of a rice MADS
      box gene in tobacco.
AB  - Floral organ development is controlled by a group of regulatory factors
      containing the MADS domain. In this study, we have isolated and characterized a
      cDNA clone from rice, OsMADS3, which encodes a MADS-domain containing protein.
      The OsMADS3 amino acid sequence shows over 60% identity to AG of Arabidopsis, PLE
      of Antirrhinum majus, and AG/PLE homologues of petunia, tobacco, tomato, Brassica
      napus, and maize. Homology in the MADS box region is most conserved. RNA blot
      analysis indicated that the rice MADS gene was preferentially expressed in
      reproductive organs, especially in stamen and carpel. In situ localization
      studies showed that the transcript was present primarily in stamen and carpel.
      The function of the rice OsMADS3 was elucidated by ectopic expression of the gene
      under the control of the CaMV 35S promoter in a heterologous tobacco plant
      system. Transgenic plants exhibited an altered morphology and coloration of the
      perianth organs. Sepals were pale green and elongated. Limbs of the corolla were
      split into sections which in some plants became antheroid structures attached to
      tubes that resembled filaments. The phenotypes mimic the results of ectopic
      expression of dicot AG gene or AG homologues. These results indicate that the
      OsMADS3 gene is possibly an AG homologue and that the AG genes appear to be
      structurally and functionally conserved between dicot and monocot.

PMID- 7579157
TI  - An unusual group 2 LEA gene family in citrus responsive to low temperature.
AB  - Six cDNAs representing unique cold-induced sequences have been cloned from the
      hardy citrus relative Poncirus trifoliata. Among these, pBCORc115 and pBCORc119
      were found to belong to the same gene family. Sequencing data indicated that
      pBCORc115 and pBCORc119 each contained an open reading frame, coding for a 19.8
      kDa protein (COR19) and a smaller 11.4 kDa protein (COR11) respectively.
      Inspection of the deduced amino acid sequences revealed three large repeats in
      COR19, but only one was present in the COR11. Two elements: a Q-clustered tract
      and a K-rich motif were identified in each repeat. The K-rich motifs were similar
      to those of cotton D-11 and Group 2 LEA proteins. A Serine-cluster, a common
      feature in many Group 2 LEA-like proteins, was also found in these proteins, but
      it was in an unusual position at the carboxy-terminus. A bipartite motif of basic
      residues, similar to known nuclear targeting sequences, was also present in COR19
      and COR11, suggesting that members of this protein family may have a nuclear
      targeting function. The expression of COR19 mRNA in response to cold acclimation,
      drought, flooding, and salinization was examined. COR19 expression in leaf tissue
      was induced in response to cold acclimation, but repressed during drought and
      flooding stress.

PMID- 7579156
TI  - Multiple cDNAs of wheat voltage-dependent anion channels (VDAC): isolation,
      differential expression, mapping and evolution.
AB  - The mitochondrial outer membrane of eukaryotic cells contains voltage-dependent
      anion channels (VDAC) also termed porins. Three cDNAs from wheat (Triticum
      aestivum) were isolated and sequenced (Tavdac 1-3). They share 65% similarity of
      their amino acid sequences, and therefore they probably represent isoforms. The
      deduced amino acid sequence of one of the cDNAs was found to be identical to the
      purified VDAC protein from wheat mitochondria [8]. Secondary structure analysis
      of the deduced amino acid sequences of the three vdac cDNAs revealed a
      characteristic alpha helix at their N-terminal and beta-barrel cylinders
      characteristic of VDAC channels. The Tavdac cDNAs are differentially expressed in
      meristematic tissues. The transcript levels of Tavdac 1 in all wheat tissues is
      at least 2.5-fold higher than Tavdac 2 and Tavdac 3. Tavdac 2 has a low level of
      expression in all floral tissues whereas Tavdac 3 is highly expressed in anthers.
      This is the first report on differential expression of vdac genes in plants. The
      Tavdac genes have been mapped on the wheat genome. Tavdac 1 is located on the
      long arm of chromosome 5, Tavdac 2 on the long arm of chromosome 1 and Tavdac 3
      on the long arm of chromosome 3. A phylogenetic reconstruction indicates that
      vdac genes underwent numerous duplication events throughout their evolution. All
      duplications occurred after the separation of plants from animals and fungi, and
      no orthologous genes are shared among phyla. Within plants, some of the vdac gene
      duplications probably occurred before the monocotydelon-dicotydelon split.

PMID- 7579159
TI  - Molecular study of a light-harvesting apoprotein of Giraudyopsis stellifer
      (Chrysophyceae).
AB  - We have isolated a gene from a library of nuclear DNA for a chlorophyll a/c
      binding protein (named Cac for chl a/c by analogy with Cab for chl a/b) of a
      chromophyte alga, Giraudyopsis stellifer, and sequenced it. The comparison of the
      deduced amino acid sequence with other chl a/c- and chl a/b-binding protein
      sequences shows that structural and functional features, i.e. the arrangement 'en
      X' of the two A and B transmembrane helices and the putative chl a-binding sites,
      are shared by both Chlorophyta and Chromophyta. Moreover, in contrast to
      Chlorophyta, a very strong identity is found among Chromophyta in the C helix
      suggesting a major function associated to this specific region. Nevertheless, the
      primary structure of the apoprotein does not seem affected by the pigment
      composition in Chromophyta. As in the few other examples currently known, we
      confirm that the cac genes are nuclear-encoded and are part of a multigenic
      family. Northern blots, performed on poly(A)+ mRNA from G: stellifer, give
      evidence that the cac gene is light-induced at a transcriptional level and that
      no expression can be observed in the dark.

PMID- 7579158
TI  - Rice scutellum induces Agrobacterium tumefaciens vir genes and T-strand
      generation.
AB  - For successful transformation of a plant by Agrobacterium tumefaciens it is
      essential that the explant used in cocultivation has the ability to induce
      Agrobacterium tumour-inducing (Ti) plasmid virulence (vir) genes. Here we report
      a significant variation in different tissues of Indica rice (Oryza sativa L. cv.
      Co43) in their ability to induce Agrobacterium tumefaciens vir genes and T-strand
      generation, using explants preincubated in liquid Murashige and Skoog (MS)
      medium. An analysis of rice leaf segments revealed that they neither induced vir
      genes nor inhibited vir gene induction. Of different parts of rice plants of
      different ages analysed only scutellum from four-day old rice seedlings induced
      vir genes and generation of T-strands. We observed that the physical presence of
      preincubated scutella is required for vir gene induction. Conditioned medium from
      which preincubated scutella were removed did not induce the vir genes. Scutellum
      derived calli, cultured for 25 days on medium containing 2,4-D, also induced virE
      to an appreciable level. These results suggest that scutellum and scutellum
      derived calli may be the most susceptible tissues of rice for Agrobacterium
      mediated transformation.

PMID- 7579160
TI  - Field trial analysis of nitrate reductase co-suppression: a comparative study of
      38 combinations of transgene loci.
AB  - Co-suppression of host genes and 35S transgenes encoding nitrate reductase was
      previously reported in transgenic tobacco plants (Nicotiana tabacum cv. Paraguay
      or Burley) using either a full-length cDNA or fragments devoid of the 3' and/or
      5' UTR. Co-suppression was previously shown to affect a limited fraction of the
      progeny of one transgenic tobacco line homozygous for a single transgene locus,
      and the phenomenon occurred at each generation. In this work, 38 combinations of
      transgene loci derived from 13 independent transgenic lines homozygous for a
      single transgene locus were field-tested under two different conditions in an
      attempt to determine the corresponding frequencies of co-suppression, i.e. the
      percentage of plants showing co-suppression. Each of the 13 homozygous lines
      exhibited a different frequency of co-suppression, ranging from 0% to 57%. High
      frequencies were found to be associated with transgene loc carrying a high number
      of copy of the transgene, suggesting a transgene dose effect. Combinations
      carrying 2 non-allelic transgene loci in a hemizygous state exhibited frequencies
      of co-suppression between those of each of the 2 transgene loci in a homozygous
      state, while combinations carrying 2 non-allelic transgene loci in a homozygous
      state exhibited frequencies of co-suppression higher than the sum of those of the
      2 transgene loci alone in a homozygous state, clearly confirming a transgene dose
      effect. Co-suppression frequencies were increased when the plants were grown
      initially in vitro, suggesting some environmental effect. The roles of transgene
      copy number, number of transgene loci and environmental factors are discussed in
      the light of a threshold hypothesis.

PMID- 7579161
TI  - Analysis of Arabidopsis cDNA that shows homology to the tomato E8 cDNA.
AB  - The negative regulatory protein of ethylene synthesis in ripening tomato fruit,
      E8, is structurally related to the enzyme that catalyzes the last step in
      ethylene synthesis, 1-aminocyclopropane-1-carboxylate (ACC) oxidase, and to a
      large family of 2-oxoglutarate-dependent dioxygenases (2-ODD). A cDNA with
      structural homology to the tomato E8 was isolated from a cDNA library of
      Arabidopsis thaliana. Sequence analysis showed that this cDNA, 2A6, encodes a
      protein of 361 amino acids. Southern blot analysis indicated that the
      corresponding gene is unique in the Arabidopsis genome. The level of the 2A6
      transcript was not increased by ethylene in siliques of Arabidopsis, as was E8 in
      tomato fruits, and was also expressed in etiolated seedlings, leaves, stems and
      flowers. The 2A6 protein shows three domains that are highly conserved among E8,
      ACC oxidases, and 2-ODDs.

PMID- 7579162
TI  - The unusual 5' splicing border GC is used in myrosinase genes of the
      Brassicaceae.
AB  - Myrosinase (thioglucosidase glucohydrolase; EC 3.2.3.1) is a group of isoenzymes
      in the Brassicaceae, which hydrolyze glucosinolates. Genes encoding myrosinase
      contain 12 exons and 11 introns. Sequence comparison of two myrosinase genes from
      Arabidopsis thaliana, TGG1 and TGG2, with the corresponding cDNA from leaves,
      showed preferential use of a GC dinucleotide as the 5' splicing border in intron
      1 instead of an adjacent GT dinucleotide four bp further 3'. This 5' GC splice
      site is conserved in all seven myrosinase genes characterized from three
      different species. Likewise, in the 3' region of intron 1 two AG dinucleotides
      are located seven bp apart. Only the most 5' of these dinucleotides was found to
      be used in splicing. Sequence analyses of TGG1 cDNA isolated from seeds, siliques
      and vegetative tissue using reverse transcription PCR showed that the splicing
      pattern of this intron is identical in these tissues for TGG1. The GT and the
      most 3' AG dinucleotides mentioned above have been assumed to be the intron
      borders of intron 1 in several myrosinase genes. The present investigation shows
      that this assumption is not correct.

PMID- 7579163
TI  - Characterisation of HEVER, a novel stress-induced gene from Hevea brasiliensis.
AB  - A novel stress-induced gene, HEVER (Hevea ethylene-responsive) from the rubber
      tree, Hevea brasiliensis, has been isolated and characterised. HEVER is encoded
      by a multigene family. The HEVER transcript is expressed at basal levels in Hevea
      tissues and is developmentally regulated. In addition, the HEVER transcript and
      protein are induced by stress treatment with salicylic acid and ethephon.
      Sequence analysis shows that HEVER encodes a 33 kDa protein that has significant
      homology to the hypothetical protein SLEXORFA-1 from the plant, Stellaria
      longipes, and two bacterial proteins, BAC180K-75 from Bacillus subtilis and
      MVRNO3-1 from Methanococcus vannielii.

PMID- 7579164
TI  - The Tokumasu radish mitochondrial genome contains two complete atp9 reading
      frames.
AB  - Two copies of the gene atp9, encoding subunit 9 of the mitochondrial F1F0-ATPase,
      have been cloned from the Tokumasu radish (Raphanus sativus L.) cytoplasm. The
      genomic DNA and the corresponding cDNA sequences of the coding regions were
      determined. Both alleles contain a 222 bp long and well conserved atp9 reading
      frame, coding for a 74 amino acid polypeptide. The Tokumasu atp9-1 gene may have
      a unique N-terminal extension of 11 amino acid residue relative to other plant
      atp9 genes. In comparison of cDNA and genomic sequences four RNA editing events
      were found in both atp9 genes. Northern experiments indicate different
      transcription patterns for the two genes.

PMID- 7579165
TI  - Evidence for some common signal transduction events for opposite regulation of
      nitrate reductase and phytochrome-I gene expression by light.
AB  - We have explored the possible involvement of the phosphoinositide (PI) cycle and
      protein kinase C (PKC) in the phytochrome (Pfr)-mediated light signal
      transduction pathway using nitrate reductase (NR) and phytochrome-I (PhyI) genes
      as model systems. We have shown earlier that phorbol myristate acetate (PMA)
      completely replaces the red light effect in stimulating nitrate reductase
      activity and transcript levels in maize. In this paper, we present detailed
      evidence to show that PMA mimics the red light effect and follows similar
      kinetics to enhance NR steady-state transcript accumulation in a nitrate
      dependent manner. We also show that PMA inhibits phyI steady-state transcript
      accumulation in a manner similar to red light, indicating that a PKC-type
      enzyme(s) may be involved in mediating the light effect in both cases. Serotonin
      or 5-hydroxytryptamine (5-HT), a stimulator of PI turnover, was also found to
      mimic the red light effect in enhancing NR transcript levels and inhibiting phyI
      transcript accumulation, indicating the role of the PI cycle in generating second
      messengers for regulating the two genes. These results indicate that phytochrome
      mediated light regulation of NR and phyI gene expression may involve certain
      common steps in the signal transduction pathway such as the PI cycle and protein
      phosphorylation by a PKC-type enzyme.

PMID- 7579166
TI  - Isolation and characterization of six heat shock transcription factor cDNA clones
      from soybean.
AB  - Thermal stress in soybean seedlings causes the activation of pre-existing heat
      shock transcription factor proteins (HSFs). Activation results in the induction
      of DNA binding activity which leads to the transcription of heat shock genes.
      From a soybean cDNA library we have isolated cDNA clones corresponding to six HSF
      genes. Two HSF genes are expressed constitutively at the transcriptional level,
      and the remaining four are heat-inducible. Two of the heat inducible genes are
      also responsive to cadmium stress. Comparative analysis of HSF sequences
      indicated higher conservation of the DNA binding domain among plant HSFs than
      those from yeast or other higher eukaryotes. The putative plant HSF
      oligomerization domain contains hydrophobic heptapeptide repeats characteristic
      of coiled coils and seems to exist in two structural variants. The carboxy
      terminal domains are reduced in size and the C-terminal heptad repeat is
      degenerate.

PMID- 7579167
TI  - Mutations in the processing site of the precursor of ribulose-1,5-bisphosphate
      carboxylase/oxygenase small subunit: effects on import, processing, assembly and
      stability.
AB  - The small subunit (SSU) of Rubisco is synthesized in the cytosol in a precursor
      form. Upon import into the chloroplast, it is proteolytically processed at a Cys
      Met bond to yield the mature form of the protein. To assess the importance of the
      Met residue for recognition and processing by the stromal peptidase, we
      substituted this residue with either Thr, Arg or Asp. The mutant precursor
      proteins were imported into isolated chloroplasts, and the products of the import
      reactions were analyzed. Mutants containing Thr or Arg residues at the putative
      processing site were processed to a single peptide, comigrating with the wild
      type protein. N-terminal radio-sequencing revealed that these mutants were
      processed at the Cys-Thr and the Cys-Arg bond, respectively. After import of the
      Asp-containing mutant, four processed forms of the protein were observed.
      Analysis of the most abundant one, co-migrating with the wild-type protein,
      demonstrated that this species was also a product of correct processing, at the
      Cys-Asp bond. All the correctly processed peptides were found to be associated
      with the holoenzyme of Rubisco, and remained stable within the chloroplast, like
      the wild-type protein. The results of this study, together with previous ones,
      suggest that proper recognition and processing of the SSU precursor are more
      affected by residues N-terminal to the processing site than by the residue on the
      C-terminal side of this site.

PMID- 7579168
TI  - Two copies of a DNA element, 'Wendy', in the chloroplast chromosome of
      Chlamydomonas reinhardtii between rearranged gene clusters.
AB  - We have characterized two copies of a 2.4 kb DNA element that we call 'Wendy', in
      the chloroplast chromosome of Chlamydomonas reinhardtii. The two copies of Wendy
      reside in different single-copy regions at opposite positions in the chloroplast
      genome. Like many mobile DNA elements, both copies of Wendy are bordered by
      inverted repeats and contain several additional degenerate copies of these repeat
      sequences in direct or inverted orientation. In addition, four basepairs are
      repeated in direct orientation. Two major open reading frames (ORFs) are
      predicted from the DNA sequence of Wendy I. These ORFs are co-transcribed from a
      promoter inside the element. The deduced amino acid sequence of the larger of
      these ORFs shares some weak similarities with sequence motifs of transposases and
      integrases of other mobile elements. Wendy II appears to be altered relative to
      Wendy I by point mutations and small deletions and insertions which destroy the
      ORFs. The leader sequence of the Wendy transcript is nearly identical with the
      leader sequence of the rbcL transcript of C. reinhardtii, but not of C. moewusii
      (where the complete Wendy was also undetectable). Furthermore, both copies of
      Wendy are bracketed by gene clusters that are separated in C. reinhardtii but are
      contiguous in C. moewusii where they exist in an inverted orientation compared
      with C. reinhardtii. Wendy was not found in any of the completely sequenced
      chloroplast genomes of rice, tobacco, pine, Euglena or Marchantia, nor in any
      other GenBank entry. Our results suggest that Wendy has invaded C. reinhardtii
      after divergence from other species. Subsequent Wendy-dependent illegitimate
      homologous or site-specific recombination events or both may have contributed to
      scrambling of the C. reinhardtii chloroplast genome relative to genomes of other
      species.

PMID- 7579169
TI  - Homologues of a vacuolar processing enzyme that are expressed in different organs
      in Arabidopsis thaliana.
AB  - Vacuolar processing enzymes (VPEs) are responsible for the maturation of seed
      proteins. These processing enzymes belong to a novel group of cysteine
      proteinases with molecular masses of 37 to 39 kDa. We isolated two genes of VPEs
      from a genomic library of Arabidopsis. The gene products were designated alpha
      VPE and beta-VPE, and they were 56% identical in terms of amino acid sequence.
      The amino acid sequences of alpha-VPE and beta-VPE were also 55% and 67%
      identical to that of castor bean VPE, respectively. The gene for alpha-VPE had 7
      introns, while that of beta-VPE had 8 introns. Northern blot analysis revealed
      that alpha-VPE is expressed in rosette leaves, cauline leaves and stems of
      Arabidopsis, while beta-VPE is predominantly expressed in the flowers and buds.
      Neither alpha-VPE nor beta-VPE is expressed in the siliques. This result strongly
      suggests that the isolated genes encode isozymes of VPE that are specific to
      vegetative organs.

PMID- 7579170
TI  - Isolation of a novel Arabidopsis ozone-induced cDNA by differential display.
AB  - We have used a reverse transcriptase polymerase chain reaction procedure
      (differential display) to isolate cDNAs corresponding to transcripts that
      accumulate in ozone-treated Arabidopsis thaliana. In this report we describe the
      characterization of an ozone-induced transcript, AtOZI1. AtOZI1 mRNA in untreated
      plants was detected at low levels in cotyledons, leaves, and flower buds and at
      higher levels in roots and mature flowers. AtOZI1 mRNA accumulation was
      transiently induced in leaves 3- to 5-fold within the first 6 h of ozone
      treatment. AtOZI1 mRNA accumulation was also transiently induced 3- to 6-fold by
      phytopathogenic Pseudomonas strains. Sequence analysis of AtOZI1 revealed that it
      encodes a 8.6 kDa basic protein that contains a putative signal peptide and two
      potential phosphorylation sites. Our results suggest that AtOZI1 represents a
      novel stress-related protein that accumulates in response to the production of
      active oxygen species.

PMID- 7579171
TI  - Site-directed mutagenesis of the enhancer region of the 780 gene promoter of T
      DNA.
AB  - Potential regulatory sequences within the enhancer-like region of the 780 gene
      promoter (Agrobacterium tumefaciens T-DNA) were identified by site-directed
      mutagenesis. Transcriptional activity of the mutated promoter was analyzed by S1
      nuclease mapping of RNA from crown gall tumors of sunflower incited using a T-DNA
      based vector. Variability in expression levels were minimized by the use of an
      internal reference gene and the pooling of at least 200 tumors per construct
      tested. This approach identified numerous sequences that influence
      transcriptional activity in either a positive or negative manner. Eight regions
      of positive influence and three of negative were identified from analysis of
      those mutations that exhibited low variability in expression (P < 0.005) and
      affected activity by at least 20%.

PMID- 7579172
TI  - Organization of soybean chalcone synthase gene clusters and characterization of a
      new member of the family.
AB  - Chalcone synthase (CHS; EC 2.3.1.74), the first committed enzyme of the
      multibranched pathway of flavonoid/isoflavonoid biosynthesis is encoded by a
      multigene family in soybean, (Glycine max L. Merrill). Our results suggest that
      this gene family comprises at least seven members, some of which are clustered.
      We have identified four chs clusters in the allo-tetraploid G. max genome and
      chs5, a newly characterized member of the chs gene family is present in two of
      them. We describe the complete nucleotide sequence of chs5, the identification of
      its immediate neighbors and the organization of the four hitherto identified chs
      clusters in the Gm genome.

PMID- 7579173
TI  - Antisense suppression of S-RNase expression in Nicotiana using RNA polymerase II-
      and III-transcribed gene constructs.
AB  - In the Solanaceae, self-incompatibility is controlled by a single, multi-allelic
      ('S') locus. One product of this locus is a ribonuclease, the S-RNase, which is
      expressed predominantly in mature pistils and has recently been shown to cause
      allele-specific pollen rejection in transgenic plants. Hybrid Nicotiana
      plumbaginifolia x N. alata plants were used to test the effects of antisense
      suppression of the SA2-RNase from N. alata using three different gene constructs:
      two driven by RNA polymerase II-transcribed promoters, and the third, containing
      a truncated soybean tRNA (met-i) gene, transcribed by RNA polymerase III. All
      three constructs caused suppression of S-RNase activity in the transgenic plants.
      Unexpectedly, the CaMV 35S promoter was more effective for antisense suppression
      than the tissue specific tomato ChiP promoter. Antisense suppression of S-RNase
      correlated with low sense SA2 transcript levels and high antisense SA2 transcript
      levels. Untransformed hybrids that contained the N. alata SA2 allele were
      incompatible with N. alata SA2 pollen, while transgenic plants with suppressed
      SA2 gene expression accepted the pollen. The utility of this hybrid plant system
      for studying some aspects of antisense gene suppression is discussed.

PMID- 7579174
TI  - A salinity-induced gene from the halophyte M. crystallinum encodes a glycolytic
      enzyme, cofactor-independent phosphoglyceromutase.
AB  - In the facultative halophyte Mesembryanthemum crystallinum (ice plant), salinity
      stress triggers significant changes in gene expression, including increased
      expression of mRNAs encoding enzymes involved with osmotic adaptation to water
      stress and the crassulacean acid metabolism (CAM) photosynthetic pathway. To
      investigate adaptive stress responses in the ice plant at the molecular level, we
      generated a subtracted cDNA library from stressed plants and identified mRNAs
      that increase in expression upon salt stress. One full-length cDNA clone was
      found to encode cofactor-independent phosphoglyceromutase (PGM), an enzyme
      involved in glycolysis and gluconeogenesis. Pgm1 expression increased in leaves
      of plants exposed to either saline or drought conditions, whereas levels of the
      mRNA remained unchanged in roots of hydroponically grown plants. Pgm1 mRNA was
      also induced in response to treatment with either abscisic acid or cytokinin.
      Transcription run-on experiments confirmed that Pgm1 mRNA accumulation in leaves
      was due primarily to increased transcription rates. Immunoblot analysis indicated
      that Pgm1 mRNA accumulation was accompanied by a modest but reproductible
      increase in the level of PGM protein. The isolation of a salinity-induced gene
      encoding a basic enzyme of glycolysis and gluconeogenesis indicates that
      adaptation to salt stress in the ice plant involves adjustments in fundamental
      pathways of carbon metabolism and that these adjustments are controlled at the
      level of gene expression. We propose that the leaf-specific expression of Pgm1
      contributes to the maintenance of efficient carbon flux through
      glycolysis/gluconeogenesis in conjunction with the stress-induced shift to CAM
      photosynthesis.

PMID- 7579176
TI  - Mitochondrial genome diversity in soybean: repeats and rearrangements.
AB  - Mitochondrial (mt) genome organization in soybean was examined at the molecular
      level. This study builds upon previous reports that four soybean cytoplasmic
      groups, Bedford, Arksoy, Lincoln, and soja-forage, are differentiated by
      polymorphisms detected with a 2.3 kb Hind III mtDNA probe [12]. The variation
      detected results from DNA alterations in a region within and around a 4.8 kb
      repeat. The Bedford-type cytoplasm is the only cytoplasm that contains copies of
      a 4.8 kb repeat in four different genomic environments, evidence that it is
      recombinationally active. The Lincoln- and Arksoy-type cytoplasms each contain
      two copies of the repeat, as well as unique fragments that appear to result from
      rare recombination events outside, but near, the repeat. The soja-forage-type
      cytoplasm contains no complete copies of the repeat, but does contain a unique
      truncated version of the repeat. Sequence analysis indicates that the truncation
      is a result of recombination across a 9 bp repeated sequence, CCCCTCCCC. The
      structural rearrangements that have occurred in the region surrounding the 4.8 kb
      repeat may provide a means to dissect species relationships and evolution within
      the subgenus soja.

PMID- 7579175
TI  - Several distinct genes encode nearly identical to 16 kDa proteolipids of the
      vacuolar H(+)-ATPase from Arabidopsis thaliana.
AB  - To understand the subcellular roles and the regulation of vacuolar H(+)-ATPases,
      we have begun to identify the genes encoding the major subunits and to determine
      their patterns of expression in Arabidopsis thaliana. Two distinct cDNAs (AVA-P1
      and AVA-P2) and one genomic sequence (AVA-P3) encoding the 16 kDa subunit have
      been isolated. The 16 kDa proteolipid is a major component of the membrane
      integral sector that forms the proton conductance pathway and is required for
      assembly of the V-ATPase complex. Interestingly, the open reading frame of one
      full-length cDNA (AVA-P1) and a genomic sequence (AVA-P3) encoded an identical
      polypeptide of 164 amino acids with a molecular mass of 16,570. The deduced amino
      acid sequences of the two cDNAs were nearly identical (99%) and hydropathy plots
      suggested a molecule with four membrane-spanning domains characteristic of V
      ATPase proteolipids. The three genes differed mainly in their codon usage and in
      their 3'-untranslated regions. The coding region of the genomic sequence, AVA-P3,
      was interrupted by two introns located at the codons for Cys-26 and Arg-121. The
      presence of additional 16 kDa proteolipid genes was suggested from several
      polymerase chain reaction (PCR)-amplified fragments that differed from one
      another in the size of the second intron. PCR 1 had an intron of ca. 800 bp and
      its identity as AVA-P4, a fourth member of the gene family, was confirmed from
      sequence analyses of an EST cDNA. The mRNAs of three genes (AVA-P1, AVA-P2 and
      AVA-P3) were detected in Arabidopsis leaf, root, flower and silique; yet
      expression of AVA-P1 and AVA-P2 was lower in roots. All three genes were
      expressed in light- or dark-grown seedlings; however mRNA levels of AVA-P2 were
      enhanced in etiolated plants. Arabidopsis thaliana, therefore, has at least four
      distinct genes encoding nearly identical 16 kDa proteolipids, and the enhanced
      expression of AVA-P2 transcript in etiolated seedlings suggests that an increase
      in V-ATPase could accompany cell expansion.

PMID- 7579177
TI  - Cell cycle regulation during growth-dormancy cycles in pea axillary buds.
AB  - Accumulation patterns of mRNAs corresponding to histones H2A and H4, ribosomal
      protein genes rpL27 and rpL34, MAP kinase, cdc2 kinase and cyclin B were analyzed
      during growth-dormancy cycles in pea (Pisum sativum cv. Alaska) axillary buds.
      The level of each of these mRNAs was low in dormant buds on intact plants,
      increased when buds were stimulated to grow by decapitating the terminal bud,
      decreased when buds ceased growing and became dormant, and then increased when
      buds began to grow again. Flow cytometry was used to determine nuclear DNA
      content during these developmental transitions. Dormant buds contain G1 and G2
      nuclei (about 3:1 ratio), but only low levels of S phase nuclei. It is
      hypothesized that cells in dormant buds are arrested at three points in the cell
      cycle, in mid-G1, at the G1/S boundary and near the S/G2 boundary. Based on the
      accumulation of histone H2A and H4 mRNAs, which are markers for S phase, cells
      arrested at the G1/S boundary enter S within one hour of decapitation. The
      presence of a cell population arrested in mid-G1 is indicated by a second peak of
      histone mRNA accumulation 6 h after the first peak. Based on the accumulation of
      cyclin B mRNA, a marker for late G2 and mitosis, cells arrested at G1/S begin to
      divide between 12 and 18 h after decapitation. A small increase in the level of
      cyclin B mRNA at 6 h after decapitation may represent mitosis of the cells that
      has been arrested near the S/G2 boundary. Accumulation of MAP kinase, cdc2
      kinase, rpL27 and rpL34 mRNAs are correlated with cell proliferation but not with
      a particular phase of the cell cycle.

PMID- 7579178
TI  - Identification of a cDNA that encodes a 1-acyl-sn-glycerol-3-phosphate
      acyltransferase from Limnanthes douglasii.
AB  - Two different techniques were used to isolate potential cDNAs for acyl-CoA: 1
      acyl-sn-glycerol-3-phosphate acyltransferase (LPA-AT) enzymes from Limnanthes
      douglasii. Both heterologous screening with the maize pMAT1 clone and in vivo
      complementation of the Escherichia coli mutant JC201 which is deficient in LPA-AT
      activity, were carried out. Clones identified by these procedures were different.
      Homology searches demonstrated that the clone isolated by heterologous probing,
      pLAT1, encodes a protein which is most similar to the maize (open reading frame
      in pMAT1) and yeast SLC1 proteins, which are putative LPA-AT sequences. This L.
      douglasii sequence shows much lower homology to the E. coli LPA-AT protein PlsC,
      which is the only LPA-AT sequence confirmed by over-expression studies. The clone
      isolated by complementation, pLAT2, encodes a protein with homology to both SLC1
      and PlsC. It was not possible to over-express the complementing protein encoded
      by pLAT2 but further experimentation on membranes from complemented JC201
      demonstrated that they possess a substrate specificity distinctly different from
      PlsC and similar to Limnanthes sp. microsome specificity. This data strongly
      supports the contention that pLAT2 is an LPA-AT clone. Northern blot analysis
      revealed different expression patterns for the two genes in pLAT1 and pLAT2.
      Transcription of the gene encoding the insert of pLAT2 occurred almost
      exclusively in developing seed tissue, whilst the cDNA of pLAT1 hybridised to
      poly(A)+ mRNA from seed, stem and leaf, demonstrating more widespread expression
      throughout the plant. Southern blot analysis indicated that the cDNA of pLAT2 was
      transcribed from a single-copy gene while that for pLAT1 was a member of a small
      gene family.

PMID- 7579180
TI  - Immunological evidence for accumulation of two high-molecular-weight (104 and 90
      kDa) HSPs in response to different stresses in rice and in response to high
      temperature stress in diverse plant genera.
AB  - Rice seedlings accumulate stainable amounts of the 104 and 90 kDa polypeptides in
      response to high temperature stress. We have purified and raised highly specific
      polyclonal antisera against both of these polypeptides. In western blotting
      experiments, we find that these proteins are accumulated to different extents in
      rice seedlings subjected to salinity (NaCl), water stress, low-temperature stress
      and exogenous abscisic acid application. These proteins also accumulated when
      rice seedlings grown in pots under natural conditions were subjected to water
      stress by withholding watering. Seedlings of Triticum aestivum, Sorghum bicolor,
      Pisum sativum, Zea mays, Brassica juncea and mycelium of Neurospora crassa showed
      accumulation of the immunological homologues of both the 104 and the 90 kDa
      polypeptides, in response to high-temperature stress. We have earlier shown that
      shoots of rice seedlings exposed to heat shock accumulate a 110 kDa polypeptide
      which is an immunological homologue of the yeast HSP 104 (Singla and Grover,
      Plant Mol Biol 22: 1177-1180, 1993). Employing anti-rice HSP 104 antibodies and
      anti-yeast HSP 104 antibodies together, we provide evidence that rice HSP 104 is
      different from the earlier characterized rice HSP 110.

PMID- 7579181
TI  - Post-translational processing of the highly processed, secreted periplasmic
      carbonic anhydrase of Chlamydomonas is largely conserved in transgenic tobacco.
AB  - The periplasmic carbonic anhydrase (CA) gene CAH1 of Chlamydomonas reinhardtii
      codes for a highly processed secreted glycoprotein. The primary translation
      product of the CAH1 gene is targeted to the ER, where it is proteolytically
      processed to yield two different subunits, glycosylated, assembled into an active
      heterotetramer, and secreted. After replacing the target leader sequence with
      that from tobacco anionic peroxidase, expression of this gene in transgenic
      tobacco plants was investigated. SDS-PAGE gels of the purified protein from
      tobacco, showed that it migrated as a series of discrete bands (two large and one
      small) with slightly faster mobility than the comparable bands in the purified
      algal protein. The expressed protein in the plant was active, and staining with
      thymol and sulfuric acid confirmed that it was also glycosylated. The periplasmic
      CA1 (peri-CA1) also was found to be enriched in the intercellular fluid of
      transgenic tobacco, indicating it was secreted. The specific activity of the
      enzyme and its sensitivity to sulfonamide inhibitors were similar to that of the
      native algal enzyme. These results suggest that the post translational processing
      of Chlamydomonas peri-CA1 is largely conserved in a higher plant.

PMID- 7579182
TI  - The in vitro assembly of the NADPH-protochlorophyllide oxidoreductase in pea
      chloroplasts.
AB  - The NADPH-protochlorophyllide oxidoreductase (pchlide reductase, EC 1.6.99.1) is
      the major protein in the prolamellar bodies (PLBs) of etioplasts, where it
      catalyzes the light-dependent reduction of protochlorophyllide to chlorophyllide
      during chlorophyll synthesis in higher plants. The suborganellar location in
      chloroplasts of light-grown plants is less clear. In vitro assays were performed
      to characterize the assembly process of the pchlide reductase protein in pea
      chloroplasts. Import reactions employing radiolabelled precursor protein of the
      pchlide reductase showed that the protein was efficiently imported into fully
      matured green chloroplasts of pea. Fractionation assays following an import
      reaction revealed that imported protein was targeted to the thylakoid membranes.
      No radiolabelled protein could be detected in the stromal or envelope
      compartments upon import. Assembly reactions performed in chloroplast lysates
      showed that maximum amount of radiolabelled protein was associated to the
      thylakoid membranes in a thermolysin-resistant conformation when the assays were
      performed in the presence of hydrolyzable ATP and NADPH, but not in the presence
      of NADH. Furthermore, membrane assembly was optimal at pH 7.5 and at 25 degrees
      C. However, further treatment of the thylakoids with NaOH after an assembly
      reaction removed most of the membrane-associated protein. Assembly assays
      performed with the mature form of the pchlide reductase, lacking the transit
      peptide, showed that the pre-sequence was not required for membrane assembly.
      These results indicate that the pchlide reductase is a peripheral protein located
      on the stromal side of the membrane, and that both the precursor and the mature
      form of the protein can act as substrates for membrane assembly.

PMID- 7579179
TI  - A novel wound-inducible extensin gene is expressed early in newly isolated
      protoplasts of Nicotiana sylvestris.
AB  - A cDNA clone (6PExt 1.2) encoding a novel extensin was isolated from a cDNA
      library made from 6 h old mesophyll protoplasts of Nicotiana sylvestris. The
      screening was performed with a heterologous probe from carrot. The encoded
      polypeptide showed features characteristic of hydroxyproline-rich glycoproteins
      such as Ser-(Pro)4 repeats and a high content in Tyr and Lys residues. The
      presence of four Tyr-X-Tyr-Lys motifs suggests the possibility for intramolecular
      isodityrosine cross-links whereas three Val-Tyr-Lys motifs may participate in
      intermolecular cross-links. The analysis of genomic DNA gel blots using both the
      N. sylvestris and the carrot clones as probes showed that the 6PExt 1.2 gene
      belongs to a complex multigene family encoding extensin and extensin-related
      polypeptides in N. sylvestris as well as in related Nicotianeae including a
      laboratory hybrid. This was confirmed by the analysis of RNA gel blots: a set of
      mRNAs ranging in size from 0.3 kb to 3.5 kb was found by the carrot extensin
      probe. The 6PExt 1.2 probe found a 1.2 kb mRNA in protoplasts and in wounded
      tissues as well as a 0.9 kb mRNA which seemed to be stem-specific. The gene
      encoding 6PExt 1.2 was induced by wounding in protoplasts, in leaf strips and
      after Agrobacterium tumefaciens infection of stems.

PMID- 7579183
TI  - Absence of PsaC subunit allows assembly of photosystem I core but prevents the
      binding of PsaD and PsaE in Synechocystis sp. PCC6803.
AB  - In photosystem I (PSI) of oxygenic photosynthetic organisms the psaC polypeptide,
      encoded by the psaC gene, provides the ligands for two [4Fe-4S] clusters, FA and
      FB. Unlike other cyanobacteria, two different psaC genes have been reported in
      the cyanobacterium Synechocystis 6803, one (copy 1) with a deduced amino acid
      sequence identical to that of tobacco and another (copy 2) with a deduced amino
      acid sequence similar to those reported for other cyanobacteria. Insertion of a
      gene encoding kanamycin resistance into copy 2 resulted in a photosynthesis
      deficient strain, CDK25, lacking the PsaC, PsaD and PsaE polypeptides in isolated
      thylakoid membranes, while the PsaA/PsaB and PsaF subunits were found. Growth of
      the mutant cells was indistinguishable from that of wild-type cells under light
      activated heterotrophic growth (LAHG). A reversible P700+ signal was detected by
      EPR spectroscopy in the isolated thylakoids during illumination at low
      temperature. Under these conditions, the EPR signals attributed to FA and FB were
      absent in the mutant strain, but a reversible Fx signal was present with broad
      resonances at g = 2.079, 1.903, and 1.784. Addition of PsaC and PsaD proteins to
      the thylakoids gave rise to resonances at g = 2.046, 1.936, 1.922, and 1.880;
      these values are characteristic of an interaction-type spectrum of FA- and FB-.
      In room-temperature optical spectroscopic analysis, addition of PsaC and PsaD to
      the thylakoids also restored a 30 ms kinetic transient which is characteristic of
      the P700+ [FA/FB]- backreaction. Expression of copy 1 was not detected in cells
      grown under LAHG and under mixotrophic conditions. These results demonstrate that
      copy 2 encodes the PsaC polypeptide in PSI in Synechocystis 6803, while copy 1 is
      not involved in PSI; that the PsaC polypeptide is necessary for stable assembly
      of PsaD and PsaE into PSI complex in vivo; and that PsaC, PsaD and PsaE are not
      needed for assembly of PsaA-PsaB dimer and electron transport from P700 to Fx.

PMID- 7579184
TI  - Isolation and functional identification of a novel cDNA for astaxanthin
      biosynthesis from Haematococcus pluvialis, and astaxanthin synthesis in
      Escherichia coli.
AB  - We succeeded in isolating a novel cDNA involved in astaxanthin biosynthesis from
      the green alga Haematococcus pluvialis, by an expression cloning method using an
      Escherichia coli transformant as a host that synthesizes beta-carotene due to the
      Erwinia uredovora carotenoid biosynthesis genes. The cloned cDNA was shown to
      encode a novel enzyme, beta-carotene ketolase (beta-carotene oxygenase), which
      converted beta-carotene to canthaxanthin via echinenone, through chromatographic
      and spectroscopic analysis of the pigments accumulated in an E. coli
      transformant. This indicates that the encoded enzyme is responsible for the
      direct conversion of methylene to keto groups, a mechanism that usually requires
      two different enzymatic reactions proceeding via a hydroxy intermediate. Northern
      blot analysis showed that the mRNA was synthesized only in the cyst cells of H.
      pluvialis. E. coli carrying the H. pluvialis cDNA and the E. uredovora genes
      required for zeaxanthin biosynthesis was also found to synthesize astaxanthin
      (3S, 3'S), which was identified after purification by a variety of spectroscopic
      methods.

PMID- 7579187
TI  - Isolation and expression pattern of a cDNA encoding a cathepsin B-like protease
      from Nicotiana rustica.
AB  - Sequence analysis of a 1.33 kb clone from a root cDNA library of Nicotiana
      rustica revealed an open reading frame encoding a protein of 356 amino acids. The
      deduced protein has high levels of homology to human cathepsin B protease and a
      cathepsin B-like cysteine protease from wheat but much lower levels of homology
      with other plant cysteine proteinases. Southern blotting experiments suggest a
      limited number of cathepsin B-like genes are present in the genome of N. rustica
      and also that of N. tabacum. RNA analysis involving a range of tissues, harvested
      from both Nicotiana species 4-5 h after the beginning of a 16 h photoperiod,
      revealed the cathepsin B-like gene was being expressed strongly in roots, stem
      and developing flowers but weakly in mature leaves. Further analysis of RNA
      extracted from leaf tissue of N. tabacum revealed the gene showed rhythmic
      expression and also that its expression increased in response to wounding.
      Analysis of leaf tissues harvested during the latter part of a 16 h photoperiod
      (11 and 16 h after illumination commenced) showed that transcript levels were two
      three times higher than in leaf tissue harvested either towards the end of the
      dark period or 5 h after illumination commenced. When leaf tissue was wounded at
      11:00 (5 h after plants were illuminated), and harvested for RNA extraction 6 h
      later, the level of cathepsin B-like transcript in mesophyll tissue was found to
      be increased ca. 2-fold relative to the level detected in unwounded controls.

PMID- 7579185
TI  - Molecular comparison of carbonic anhydrase from Flaveria species demonstrating
      different photosynthetic pathways.
AB  - During the evolution of C4 plants from C3 plants, both the function and
      intracellular location of carbonic anhydrase (CA) have changed. To determine
      whether these changes are due to changes at the molecular level, we have studied
      the cDNA sequences and the expression of CA from Flaveria species demonstrating
      different photosynthetic pathways. In leaf extracts from F. bidentis (C4), F.
      brownii (C4-like), F. linearis (C3-C4) and F. pringlei (C3), two polypeptides of
      M(r) 31 kDa and 35 kDa cross-reacted with anti-spinach CA antibodies. However,
      the relative labelling intensities of the two polypeptides differed depending on
      the species. Northern blot analysis indicated at least two CA transcripts are
      present in each Flaveria species with sizes ranging from 1.1 to 1.6 kb. Carbonic
      anhydrase cDNAs from all four Flaveria species studied encode an open reading
      frame for a polypeptide of 35-36 kDa. The amino acid sequences deduced from all
      four Flaveria cDNAs share at least 70% homology with the sequences of other dicot
      CAs. The F. bidentis (C4) CA sequence was found to be the least similar of the
      Flaveria proteins and, as most of the sequence dissimilarity was found in the
      first third of the CA molecule, these differences may be involved in the
      intracellular targeting of CA. A neighbour-joining tree inferred from CA amino
      acid sequences showed that the Flaveria CAs cluster with other dicot CAs forming
      a group distinct from those of monocot CAs and prokaryotic and Chlamydomonas
      periplasmic CAs.

PMID- 7579186
TI  - Abundance and half-life of the distinct oat phytochrome A3 and A4 mRNAs.
AB  - Gene-preferential oligonucleotide probes were used to determined the relative
      abundance and half-lives of distinct oat phytochrome A (PHYA) mRNAs. Oat PHYA
      mRNAs are highly conserved in the 5'-untranslated region and the coding region,
      but the 3'-untranslated region has an overall lower sequence conservation and was
      the source of gene-preferential probes. PHYA3 mRNA was estimated to be ca. 61% of
      the oat PHYA mRNA pool present in poly(A)+ RNA from dark-grown seedlings. The
      half-lives for PHYA3 and PHYA4 mRNAs were both estimated to be ca. 30 min, and a
      similar short half-life was estimated for the average PHYA mRNA. Sequence
      comparisons of PHYA mRNAs from four grass species identified conserved sequences
      within the 5'- and 3'-untranslated regions that might be important for PHYA mRNA
      degradation.

PMID- 7579189
TI  - Structure and organization of two closely related low-temperature-induced
      dhn/lea/rab-like genes in Arabidopsis thaliana L. Heynh.
AB  - We have isolated a 7 kb EcoRI genomic fragment from Arabidopsis thaliana which
      contains, in a tandem arrangement, two closely related dhn/lea/rab-like genes,
      lti29 (formerly named lti45) and cor47, corresponding to previously isolated cDNA
      clones. Both transcripts have been shown to accumulate in response to low
      temperature (LT), abscisic acid (ABA) and dehydration. Alignment of the amino
      acid sequences of the deduced polypeptides showed that they are 67% identical.
      The calculated molecular masses of the two polypeptides were 29 kDa for LTI29 and
      30 kDa for COR47. Both polypeptides contain one conserved serine-stretch and
      three lysine-rich repeats characteristic of DHN/LEA/RAB-like proteins. In
      addition, both LTI29 and COR47 harbour and N-terminal acidic repeat only found in
      a few members amongst the DHN/LEA/RAB proteins. The close distance between the
      two genes (separated by 2.7 kb) and their tandem organization in the A. thaliana
      genome as well as the overall homology at the nucleotide sequence level of the
      coding region suggest that the two genes have evolved through a duplication
      event. This seems to be a common feature among A. thaliana LT-responsive genes.

PMID- 7579188
TI  - Evidence for the involvement of ethylene in the expression of specific RNAs
      during maturation of the orange, a non-climacteric fruit.
AB  - Twelve cDNAs corresponding to mRNAs inducible by ethylene were isolated by
      differential screening of a cDNA library from ethylene-treated Citrus sinensis
      fruits. Northern analysis of RNA extracted from flavedo of ethylene-treated
      fruits and from fruits at different maturation stages showed that some of the
      mRNAs corresponding to these cDNAs were regulated both by ethylene treatment and
      during fruit maturation. The effect of exogenous ethylene on leaves and of
      endogenous ethylene on flowers showed that gene induction was not restricted to
      the flavedo tissue. The possible role of ethylene during maturation of the non
      climacteric Citrus fruit is discussed.

PMID- 7579190
TI  - beta-1,3-Glucanase is highly-expressed in laticifers of Hevea brasiliensis.
AB  - Clones encoding beta-1,3-glucanase have been isolated from a Hevea cDNA library
      prepared from the latex of Hevea brasiliensis using a probe Nicotiana
      plumbaginifolia cDNA encoding beta-1,3-glucanase, gnl. Nucleotide sequence
      analysis showed that a 1.2 kb Hevea cDNA encoding a basic beta-1,3-glucanase
      showed 68% nucleotide homology to gnl cDNA. Northern blot analysis using the
      Hevea cDNA as probe detected a mRNA of 1.3 kb which was expressed at higher
      levels in latex than in leaf. In situ hybridization analysis using petiole
      sections from Hevea localized the beta-1,3-glucanase mRNA to the laticifer cells.
      Genomic Southern analysis suggested the presence of a low-copy gene family
      encoding beta-1,3-glucanases in H. brasiliensis.

PMID- 7579191
TI  - Expression and in vitro targeting of a sunflower oleosin.
AB  - Two distinct cDNAs encoding oleosins (oil body proteins) have been identified by
      degenerate PCR as transcripts present in the developing seeds of sunflower
      (Helianthus annuus L. cv. Dwarf Sunbred). One (pSOM) of these is closely related
      to a reported sunflower oleosin, whilst the other (pSO5) has not been previously
      described. Different expression patterns were observed for the two cDNAs, pSO5
      being expressed earlier than pSOM in seed maturation and oil deposition. The
      results support the contention that oleosin proteins are synthesised either
      during or closely after the formation of the oil body. Translation in vitro of
      synthetic oleosin transcripts was enhanced by the addition of microsomes but
      suppressed by the addition of purified signal recognition particle (SRP) complex.
      Deletion of 62 amino acid residues at the C-terminus of the oleosin did not alter
      the in vitro targeting of the protein to the microsomal membrane. Taken together
      these data support the idea that oleosins are targeted to the ER membrane as part
      of oil body biogenesis.

PMID- 7579192
TI  - Inhibitory effects of class I molecules on murine NK cells: speculations on
      function, specificity and self-tolerance.
AB  - This review addresses the physiological role of class I-mediated inhibition of NK
      cell lysis. It is suggested that several distinct activating receptors can
      stimulate NK lysis, all of which can be inhibited by class I molecules on the
      target cell. Evidence that most or all peptides that bind a class I molecule can
      cause inhibition is discussed, supporting a model in which NK cells detect loss
      of class I molecules, rather than loss of specific peptide/class I complexes.
      Finally, the acquisition of self-tolerance among NK cells is addressed with
      respect to data suggesting that autoaggressive NK cells are not deleted but
      rather exhibit altered characteristics which may render them unable to lyse
      autologous cells.

PMID- 7579193
TI  - Missing self recognition by natural killer cells in MHC class I transgenic mice.
      A 'receptor calibration' model for how effector cells adapt to self.
AB  - It is now clear that NK cells can perform 'missing self' recognition, that is
      eliminate cells because these fail to express certain critical MHC class I
      products adequately. Although isolated NK cell subsets can be turned off by self
      as well as non-self MHC molecules, genetic studies, mainly in vivo, argue that NK
      cells always learn to spare cells expressing critical self MHC alleles. This
      article reviews work on receptor expression and specificity of NK cells in MHC
      class I transgenic mice. A 'receptor calibration' model is proposed to account
      for how NK cells can interact with self as well as non-self MHC and adapt their
      receptors to perform optimally to detect alterations of self MHC.

PMID- 7579195
TI  - Development of human NK cells from the immature cell precursors.
AB  - Recent studies provided evidence that functional NK lymphocytes can be derived in
      vitro from immature cell precursors present in embryonic liver or postnatal
      thymus. In addition, by applying appropriate culture conditions a lymphoid cell
      population sharing NK and T-cell properties could be obtained from immature
      thymic cell precursors. Moreover, the molecular analysis of TCR/CD3 genes
      revealed that this cell population could represent a frozen stage of the T-cell
      lymphoid maturation. Altogether, these findings support the concept that a common
      precursor exists for T and NK cell lineages. In addition the availability of
      culture conditions which mimic the in-vivo microenvironment required for NK cell
      maturation may be important to investigate the role of self HLA in the selection
      of NK lymphocytes equipped with surface receptors specific for autologous HLA
      class I alleles.

PMID- 7579194
TI  - Hybrid resistance: 'negative' and 'positive' signaling of murine natural killer
      cells.
AB  - Murine NK cells can reject allogenic or parental-strain bone marrow cells (BMC)
      in vivo and can lyse T lymphoblasts in vitro. The 'missing self' hypothesis
      states that absence or presence of 'negative signals' from target cell class I
      antigens (Ag) to NK receptors determines whether or not lysis occurs. Indeed,
      lysis of parental-strain blasts by purified F1 NK cell subsets occurred only in
      the presence of anti-receptor antibodies. Evidence for 'positive signaling' to NK
      cells by class I Ag includes rejection of D8 (Dd) transgene to B6) BMC by B6
      hosts. The outcome of other BMC transplants contradict the missing self idea,
      because donors with identical class I Ag differ in compatibility with certain
      hosts. Perhaps class I Ag-NK cell receptor interactions dominate over other
      target-NK cell interactions. These interactions are usually 'negative' but can be
      'positive'.

PMID- 7579196
TI  - Receptors for HLA class I molecules in human NK cells.
AB  - Recent studies have shown that NK cells recognize HLA-class I molecules.
      Moreover, the analysis of NK cell clones has provided evidence that they are
      capable of discriminating between different groups of HLA alleles. HLA class I
      recognition generates a negative signal which inhibits the NK cell cytotoxicity,
      thus resulting in target cell protection. HLA-class I recognition is mediated by
      clonally distributed receptors, some of which have been identified, characterized
      and cloned. The first two identified receptors were shown to be specific for HLA
      C alleles, each recognizing a group of alleles sharing two amino acidic positions
      (77 and 80) in the peptide binding groove. The HLA-C specific receptors are
      represented by two 58 Kd (p58) molecules that are highly homologous, as shown by
      both biochemical analysis and by the comparison of the corresponding genes. Two
      additional receptors have been recently identified, which recognize two distinct
      groups of HLA-B alleles. These receptors are represented by the CD94 and by the
      NKB1 molecules, recognizing the Bw6 and Bw4 supertypic specificities. Recent
      analysis of the surface receptors involved in NK cell triggering has provided
      evidence that class I specific NK receptors can, in some instances, induce NK
      cell triggering, thus contributing to the activatory pathway of NK cells.

PMID- 7579198
TI  - Natural killer cells wear different hats: effector cells of innate resistance and
      regulatory cells of adaptive immunity and of hematopoiesis.
AB  - Natural killer (NK) cells were originally defined by their ability to lyse tumor
      cells or virus-infected cells and identified as one type of effector cells of the
      non-antigen specific innate resistance. However, many recent studies have widened
      the interpretation of the role of NK cells in immunity and shown that NK cells
      have important regulatory roles in innate resistance, antigen-specific adaptive
      immunity, and, possibly, in hematopoiesis. These functions of NK cells more than
      on their cytotoxic activity, are probably dependent on their ability to produce
      lymphokines, particularly interferon-gamma (IFN-gamma). NK cells are important
      for antigen-independent activation of phagocytic cells early in infection and for
      favoring the development of antigen-specific T helper cells type I, producing IFN
      gamma and IL-2. A role for NK cells in suppression of hematopoiesis and in
      induction of septic shock may represent a pathological exaggeration of the
      physiologic functions of NK cells in innate resistance.

PMID- 7579197
TI  - NK cell recognition of major histocompatibility complex class I molecules.
AB  - Interactions between membrane receptors on NK cells and major histocompatibility
      complex (MHC) class I molecules on target cells inhibit NK cell-mediated
      cytotoxicity. In the mouse, receptors encoded by genes of the Ly-49 family bind
      certain polymorphic H-2 molecules and prevent lysis of normal hematopoietic cell
      targets. While a human homolog of Ly-49 has not been identified as yet, two
      structurally distinct NK cell-associated membrane glycoproteins, NKB1 and p58,
      have been implicated in the recognition of polymorphic HLA-B and HLA-C molecules,
      respectively. Recent studies indicate that human NK cell clones express multiple
      receptors for HLA class I molecules and suggest that these receptors may operate
      independently when expressed in a single NK cell clone.

PMID- 7579199
TI  - A family of murine NK cell receptors specific for target cell MHC class I
      molecules.
AB  - The Ly-49A molecule is an NK cell receptor specific for MHC class I molecules on
      target cells. When Ly-49A engages H-2Dd, Ly-49A+ NK cells become globally
      incapable of killing their targets in vitro. This interaction also occurs in
      vivo. Ly-49A belongs to a family of highly related molecules, including Ly-49C
      (5E6 antigen) and LGL-1 that also determine NK cell specificity. In the NK gene
      complex, the Ly-49 family is genetically linked to genes encoding NKR-P1 and CD69
      that are structurally related and capable of activating NK cells. Finally, Ly-49
      may be related to human molecules that are selectively expressed on NK cells and
      influence NK cell specificity. These findings highlight the emerging significance
      of the Ly-49 family in NK cell activity.

PMID- 7579200
TI  - B-lymphoid potential in pre-liver mouse embryo.
AB  - Increasing interest in the initial steps of hemopoiesis in the embryo is prompted
      by the lack of information about the primordial origin and the nature of
      hemopoietic stem cells. It appears critical to understand the emergence,
      diversification and differentiation potential of hemopoietic cells in the
      preliver embryo. In-vitro studies of B-potential in the mouse embryo prior to
      liver colonization show that, contrary to interpretations prevalent 10 years ago,
      there are two sources of B-cell progenitors (and most probably stem cells) at
      these stages: the yolk sac and the paraaortic splanchnopleura within the embryo
      proper. The analysis of the phenotype and differentiation potential of precursors
      from both sources shows them to be very similar, while different from the fetal
      liver progenitors. Indications for an independent generation of precursors in
      both sites are reviewed.

PMID- 7579201
TI  - In-vitro models of B-lineage commitment.
AB  - The development of mature B lymphocytes from multipotent progenitors follows a
      pathway of differentiation marked by a progressive restriction in lineage
      options. The requirements for progression through the B lineage developmental
      pathway have been investigated intensively and a number of critical components of
      the differentiation process have been identified. However, the genetic basis for
      lineage determination remains unresolved. Recently, a number of in-vitro assays
      have been established which support the development of committed B cell
      progenitors from multipotent cells. These assays have provided a novel system in
      which the process of B lineage commitment can be followed and manipulated. In
      this review we present a model of B-lineage progression from multipotent
      progenitors to committed B-cell progenitors and discuss potential mediators of
      the commitment process.

PMID- 7579203
TI  - In-vitro models of stroma-dependent lymphopoiesis.
AB  - The differentiation of hematopoietic stem cells into lymphocytes can be
      replicated ex vivo under the inductive influence of the stromal cells that frame
      the bone marrow and thymus. We summarize hereafter the development of culture
      systems where lymphopoiesis-supporting cell compartments are maintained in either
      their normal three-dimensional arrangement, in organotypic culture, or as culture
      dish-adherent monolayers and review the recent and current uses of those in-vitro
      models to investigate T- and B-cell differentiation in mouse and man.

PMID- 7579202
TI  - In-vitro analyses of mechanisms of B-cell development.
AB  - B-cell lymphopoiesis in vivo is very complex due to the influences of cooperating
      cells, cytokines and other receptor-ligand interactions which appear to occur
      developmentally at different cellular stages. Therefore in-vitro models will help
      to unravel this complex situation. Here, we review our and others' work on in
      vitro models of B-cell development. The role of stromal cells, cytokines,
      surrogate light chain and products of rearranged Ig-loci in the developmentally
      different cellular stages will be discussed.

PMID- 7579204
TI  - The role of the thymus during T-lymphocyte development in vitro.
AB  - To date, fetal thymic organ culture is the only in-vitro system capable of
      supporting a complete programme of T-lymphocyte development in a manner
      comparable to that seen in vivo. In this review, we will summarise recent studies
      in which thymic organ cultures have been used to investigate the regulatory
      mechanisms of particular stages of thymocyte development. In addition, the use of
      other culture systems of T-cell maturation will be discussed in an attempt to
      define the optimal conditions for T-cell development in vitro.

PMID- 7579205
TI  - Making the in-vitro model closer to actual B lymphopoiesis in the bone marrow.
AB  - After more than a decade since Whitlock and Witte established an in-vitro long
      term culture of bone marrow B lineage cells, c-kit+IL-7-receptor(R)+B precursor
      cells in fresh bone marrow are now able to be grown under a fully defined culture
      condition containing only BSA, transferrin, IL-7 and the ligand for c-kit(Kit
      ligand;KL) as protein components. On the other hand, previous studies indicated
      that the actual intramarrow B-cell-genesis is a complex process involving
      multiple stromal cell-derived molecules. Thus, the next step for the culture of B
      cell genesis is to develop this simple culture into a new defined culture of B
      cell-genesis that is closer to the actual process. In this article, we will
      describe how this defined culture condition has developed from the original
      Whitlock-Witte type culture, how the B precursors under this culture-condition
      are different from that in the bone marrow, and finally our biased view on the
      future direction to which this defined culture should develop.

PMID- 7579206
TI  - Lymphohematopoietic development from embryonic stem cells in vitro.
AB  - Differentiation induction from embryonic stem (ES) cells to blood cells is one of
      the best systems to study the molecular mechanisms which are involved in the
      development and differentiation of lymphohematopoietic cells. Several systems
      including our new system (OP9 system) using a macrophage colony stimulating
      factor-deficient stromal cell line named OP9 are discussed in this paper. It is
      advantageous that the OP9 system does not require any exogenous growth factors or
      a complex embryoid structure for the induction. The OP9 system combined with
      genetic manipulation of ES cells should facilitate to elucidate molecular
      mechanisms during development and differentiation of blood cells including B
      lineage cells.

PMID- 7579207
TI  - Dependence of water conductivity on pressure and temperature in plant stems.
AB  - The effects of pressure and temperature on water conductivity were examined in
      okra stem segments. Segments were incubated in various concentrations of sorbitol
      solution at various temperatures. Water was found to pass mainly through the
      lateral side of the segments. The shrinkage rate was found to be proportional to
      the difference in the water potential between the inside of the cells and the
      ambient solution, while the rate was inversely proportional to the viscosity of
      water, which is a function of temperature. The nature of the media for water
      conductivity was found to be consistent with Darcy's law and with Hagen
      Poiseuille's law with a rough approximation. An attempt was made to estimate the
      size of the water path. Okra stem segments were incubated with and without the
      plant hormone auxin before transference to sorbitol solution. Shrinkage rates of
      segments showed that auxin caused an increase in water conductivity and thus the
      size of the water path.

PMID- 7579209
TI  - Flow in T-bifurcations: effect of the sharpness of the flow divider.
AB  - The local geometry of a bifurcation has been hypothesized to be a potential
      geometrical risk factor for the development of atherosclerosis. While flow
      division and branch area ratios clearly affect the flow field, the importance of
      the flow divider shape is not as clear. A fast spectral element computational
      fluid mechanics (CFD) solver was used to simulate flow through 90 degrees T
      bifurcations with three different flow divider shapes. Other factors, such as
      flow partition, area ratio, and bifurcation angle, were kept constant. A Reynolds
      number range of 15 to 350 was studied to bracket experimental results in the
      literature. The variation in the sharpness of the corners had a dramatic effect
      on both the flow field and wall shear stress distribution in the side branch, but
      little effect on the flow in the main tube. The magnitude of reverse velocities
      and wall shear stress in the side branch increased linearly over a physiological
      range of Reynolds number and corner shape. This paper verifies the accuracy and
      usefulness of spectral element CFD in studying three-dimensional hemodynamics.

PMID- 7579208
TI  - Solvent effects on the viscoelastic behavior of porcine submaxillary mucin.
AB  - Rheological methods have been used to investigate the intermolecular interactions
      of porcine submaxillary mucins (PSM) in solution. PSM is a high molecular weight
      glycoprotein consisting of a linear, semi-flexible protein backbone to which a
      large number of oligosaccharides (1-5 saccharide units) are attached as side
      chains. Concentrated aqueous solutions of PSM containing different amounts of
      guanidine hydrochloride (GdnHCl) were subjected to both controlled stress and
      controlled strain rheological analyses. In the absence of GdnHCl, PSM solutions
      exhibit viscoelastic properties characteristic of a gel: the storage modulus, G',
      is much larger than the loss modulus, G", at all deformation frequencies, and the
      compliance is 100% recoverable at small stresses, indicative of strong
      intermolecular interactions. In 3.0 M aqueous GdnHCl, PSM forms a viscoelastic
      solution, with G" > G' at all frequencies and a relatively small recoverable
      compliance, pointing to disruption of the intermolecular interactions by the
      chaotropic salt. Intermediate behavior is observed in 1.5 M GdnHCl,
      characteristic of a marginal gel: G' approximately G" and greater than 50%
      recoverable compliance. In dilute solution, PSM behaves viscoelastically as a
      typical polyelectrolyte. However, concentrated solutions are turbid, the
      turbidity decreasing as GdnHCl is added, indicating that extensive intermolecular
      association accompanies the gelation process. The results show that although PSM
      is secreted in nature as a viscous solution, it can form gels that are similar to
      those of tracheobronchial and gastric mucins, and suggest common features to the
      gelation mechanism, with the strength of the gel correlated with the length of
      the oligosaccharide side chains.

PMID- 7579210
TI  - Measurement of oscillatory flow pressure gradient in an elastic artery model.
AB  - In vitro experiments were conducted to measure the oscillatory flow pressure
      gradient along an elastic tube in order to assess the recent nonlinear theory of
      Wang and Tarbell. According to this theory, in an elastic tube with oscillatory
      flow, the mean (time-averaged) pressure gradient cannot be calculated using
      Poiseuille's law. The effect of wall motion creates a nonlinear convective
      acceleration, and an induced mean pressure gradient is required to balance the
      convective acceleration. The induced mean pressure gradient depends on the
      diameter variation over a cycle, the pulsatility and unsteadiness of the flow,
      and the phase difference between the pressure wave form and the flow wave form.
      The amplitude of the pressure gradient also depends on these parameters and may
      deviate significantly from Womersley's rigid tube theory. A flow loop was
      constructed to produce oscillatory flow in an elastic tube. Flow wave forms were
      measured with an ultrasonic flow probe, and ultrasonic diameter crystals were
      used to measure wall movement. A special device for pressure drop measurement was
      constructed using Millar catheter tip transducers to obtain both forward and
      backward pressure drops that were then averaged. This averaging method eliminated
      the static error of the pressure transducers. The pressure-flow phase angle was
      varied by clamping a distal elastic section at various locations. Pressure
      gradients were obtained for a range of phase angles between -55 degrees and +49
      degrees. The mean and amplitude of the measured pressure gradient were compared
      to theoretical values. Both positive and negative induced mean pressure gradients
      were measured over the range of phase angles. The measured pressure gradient
      amplitudes were always lower than predicted by Womersley's rigid tube theory. The
      experimental means and amplitudes are in good agreement with the elastic tube
      theoretical values. Thus, the experiments verify the theory of Wang and Tarbell.

PMID- 7579211
TI  - Analysis of the strain and stress distribution in the wall of the developing and
      mature rat aorta.
AB  - The variation of wall stress distribution with age in the thoracic and abdominal
      aortas of normotensive rats was studied. Dimensions of the zero-stress
      configurations were measured at the ages of 4, 8, 12, 20, and 52 weeks. Using
      data from previously published inflation tests, the circumferential stress-strain
      relationship was obtained in each age group. The calculated stress distribution
      showed that the average circumferential stress remained practically constant
      after the age of 20 weeks. The circumferential stress at the innermost part of
      the arterial wall was greater than the stress at the outermost part, but the
      difference was maintained at a moderate level with adjustments in the zero-stress
      configuration. It is speculated that, after the age of 20 weeks, changes in
      arterial geometry and rheological properties tend to maintain a constant stress
      distribution under varying conditions of loading. This distribution was achieved
      by enhanced growth at the inner part of the media in comparison with the growth
      at its outer margins and suggests that during development and maturity, the
      growth of the aorta is modulated by circumferential stress.

PMID- 7579212
TI  - Monitoring of erythrocyte aggregate morphology under flow by computerized image
      analysis.
AB  - The morphology of red blood cell (RBC) aggregates was studied by direct
      visualization of RBC aggregation at different flow conditions in a computerized
      image analyzer. The aggregate morphology is expressed by an Aggregate Shape
      Parameter (ASP), defined as the ratio of the aggregate projected area to its
      square perimeter. Aggregation was induced by either dextran-70 (m.w. 70,000) or
      dextran-500 (m.w. 500,000), and compared to that in plasma. It was found that the
      aggregate morphology is a characteristic of the aggregating agent--in dextran
      500, the RBC form rouleau aggregates as in plasma, while in dextran-70, they form
      clusters. In each system, while maintaining the overall typical morphology, the
      ASP decreases (i.e., the aggregate becomes longer) as the aggregate size is
      increased. The distribution of the ASP as a function of the aggregate size
      remains unchanged when the aggregate size is changed by modulation of the dextran
      concentration or the shear stress. Stretching of a rouleau aggregate by
      application of shear stress is reflected by a corresponding change in the ASP. It
      is suggested that the ASP is a characteristic of intercellular interactions. A
      theoretical model is proposed for evaluation of the deviation of aggregate shape
      from that of rouleau structure.

PMID- 7579213
TI  - [Tumorous space-occupying lesions of the pelvic skeleton. A radiological analysis
      of 234 cases].
AB  - PURPOSE: From the material of a bone tumour record file, an attempt was made to
      determine criteria enabling radiographic prediction of malignancy and tumour
      entity of lesions of the pelvis. METHODS: Patients' age, location and
      radiographic morphology of 234 space-occupying lesions of the pelvis were
      analysed retrospectively. RESULTS: 62.8% of all lesions were malignant, and the
      portion of malignant tumours increased with increasing age. While 68.0% of the
      lesions were found in the ilium, 18.8% in the pubis and 13.2% in ischium, the
      proportion of benign and malignant lesions did not vary in the different bones.
      Lesions showing a growth rate according to Lodwick grade IA and to IB were benign
      in 100% and in 82.0%, respectively. In contrast, tumours of grade II or III were
      malignant in 89.1% and 88.0% of cases, respectively. CONCLUSIONS: By the
      construction of subgroups by combining the patients' age and growth rate, the
      prediction of the malignant potential of a lesion increased significantly. The
      younger the patient, the more aggressively a benign lesion may grow, while the
      older the patient the slower a malignant tumour may grow. Prediction of the
      tumour entity is rarely possible.

PMID- 7579215
TI  - [A comparative study of the imaging quality and picture dosage of a new
      conventional film-screen system for skeletal x-ray diagnosis].
AB  - PURPOSE: This paper compares a new film-screen system (FSS) called INSIGHT
      Skeletal Imaging System with the previously used Lanex/T-MAT G FSS. MATERIAL AND
      METHODS: Using a Bronder phantom, measurements were made of dose, resolution and
      contrast. 135 skeletal phantom images were assessed in order of quality by six
      observers. RESULTS: Comparable high resolution film-screen combinations (FSC)
      showed similar geometric resolution. Comparing high intensifying screens, the new
      INSIGHT Skeletal Regular FSS showed better resolution than the Lanex medium FSC.
      Dose reduction for the INSIGHT Skeletal Imaging FSS was 29-56%. The new FSS
      showed image quality similar to high resolution screens but was significantly
      better when using high intensifying screens. CONCLUSION: The new INSIGHT Skeletal
      Imaging System can replace the Lanex/T-MAT G FFS by retaining quality but
      reducing radiation dose by 29-56%. Using the new high intensifying FSC, images
      showed in addition improved film quality.

PMID- 7579214
TI  - [The use of an asymmetric film-screen combination for the imaging of round
      pulmonary foci].
AB  - PURPOSE: To examine the diagnostic advantages of an asymmetric film-screen system
      (a-FSS) compared to a conventional 200-speed FSS with and without anatomical lung
      filter. METHODS: Standard radiographs were obtained from an anthropomorphic chest
      phantom with simulated pulmonary nodules. The existence or non-existence of
      nodules was assessed in 7344 individual observations. The results were evaluated
      using ROC analysis. RESULTS: In an overall evaluation the a-FSS with an ROC area
      of 0.873 +/- 0.018 was not significantly superior (p > 0.05) to the lung filter
      but significantly superior (p < 0.05) to the 200-speed FSS. In the mediastinum
      the a-FSS and the lung filter were significantly superior (p < 0.05) to the 200
      speed FSS. In the lung areas the 200-speed FSS and the a-FSS attained equivalent
      results (p > 0.05), whereas the lung filter was rated significantly lower (p <
      0.05). CONCLUSIONS: Asymmetric FSS improves chest diagnostics, because it yields
      significantly more diagnostic information in the mediastinum using equivalent x
      ray exposure without reducing the image quality in the lung areas in respect of
      simulated pulmonary nodules.

PMID- 7579216
TI  - [The potentials of digital image-intensifier radiography exemplified by digital
      spot imaging (DSI)].
AB  - PURPOSE: We performed a comparative study of digitally and conventionally
      acquired images in gastrointestinal examinations. MATERIAL AND METHODS: Radiation
      dose and spatial resolution were determined in a water phantom. In 676
      examinations with either conventional or digital imaging (system: Diagnost 76,
      DSI) the number of images and the duration of the fluoroscopy time were compared.
      101 examinations with digital as well as conventional documentation were
      evaluated by using 5 criteria describing the diagnostic performance. RESULTS: The
      entrance dose of the DSI is 12% to 36% of the film/screen system and the spatial
      resolution of the DSI may be better than that of a film/screen system with a
      speed of 200. The fluoroscopy time shows no significant difference between DSI
      and the film/screen technique. In 2 of 4 examination modes significantly more
      images were produced by the DSI. With exception of the criterion of edge
      sharpness, DSI yields a significantly inferior assessment compared with the
      film/screen technique. CONCLUSION: The DSI system was well integrated in the
      daily routine of gastrointestinal examinations. Low dose imaging, direct
      availability of images and dynamic studies with a frame rate up to 8 images per
      second are the advantages of the DSI. The lower spatial resolution in some cases
      is a diagnostic disadvantage that can reduce the diagnostic information.

PMID- 7579217
TI  - [Spiral CT angiography after the application of an iliac artery stent].
AB  - PURPOSE: To evaluate the diagnostic and clinical value of CT-A performing MIP-
      and SSD-reformations after intraarterial iliac stent application. METHODS: In a
      prospective study 32 patients underwent CT-A after stent placement in the iliac
      arteries. The vascular morphology was analyzed regarding neointimal hyperplasia
      and calcification pattern. The results were compared with those of clinical
      findings (walking distance), Doppler ultrasound (ankle-brachial index) and DSA.
      RESULTS: All 47 stents were visible and patent (100%). One misplacement was
      identified. A good correlation was found between an improved ankle-brachial index
      and CT-A (88.5%) and extension of the walking distance and CT-A (92.3%).
      Concerning location, number and grade of stenoses the results between CT-A and
      DSA matched in 42.1%. An exact mapping of calcified plaques was possible in all
      cases. CONCLUSIONS: CT-A as MIP is shown to be superior than DSA with regard to
      calcifications. Complementary to the indirect methods of the ankle-brachial index
      and walking distance, CT-A is useful for therapy control after vascular stent
      placement.

PMID- 7579218
TI  - [The magnetic resonance tomography of Ewing's sarcomas: the morphology and tumor
      extension].
AB  - PURPOSE: The morphology and delineation of Ewing sarcoma in magnetic resonance
      imaging was investigated. METHODS AND MATERIALS: Magnetic resonance images (spin
      echo techniques; T1-w pre/post gadolinium, T2-w) of 59 patients as part of a
      multicenter study were evaluated retrospectively. Qualitative image analysis was
      performed: signal intensity (point of reference extraosseous: muscle,
      intraosseous: bone marrow), enhancement patterns, lesion delineation and
      differentiation between tumor and oedema. RESULTS: Signal intensity: T1-w:
      extraosseous: 75% isointense, intraosseous: 92% hypointense; T2-w extraosseous:
      100% hyperintense, intraosseous: 93% hyperintense. Enhancement pattern: 97% both
      extra- and intraosseous. Best delineation intraosseous in T1-w (53% good, 36%
      very good), extraosseous in gadolinium enhanced T1-w (46% good, 37% very good)
      and T2-w (55% good, 33% very good). Differentiation between tumour and oedema was
      intraosseous not possible, extraosseous in T2-w in 61%. CONCLUSION: Morphology of
      Ewing sarcoma in magnetic resonance imaging is rather uniform. The lesion is
      intra- and extraosseous sharply delineated, though tumour and oedema can be
      rarely differentiated.

PMID- 7579219
TI  - [The magnetic resonance tomographic optimization of hip joint cartilage
      visualization by the selection of a T1-volume gradient-echo sequence and the use
      of hip-joint traction].
AB  - PURPOSE: The purpose of this study was to examine the accuracy of MR imaging of
      the healthy and the arthrotically altered articular hip cartilage with in vivo
      and in vitro separation of femoral head cartilage and acetabular cartilage.
      MATERIAL AND METHODS: Images of three animal cadaver hips, 8 dissected patient
      femoral heads and 18 hip joints of human corpses, all either with arthrosis stage
      I-III or artificial cartilage defects, were compared with their corresponding
      anatomic sections. Additional histomorphologic examinations of the arthrotic
      cartilages were conducted, and MR-Imaging of 20 healthy and 21 arthrotic patient
      hips was performed using a specific traction method. RESULTS: Using a T1-weighted
      3-dimensional gradient-echo sequence and a traction of the hip joint, it was
      possible due to the low-signal imaging of the joint space to separate in vivo the
      high-signal femoral head cartilage from the high-signal acetabular cartilage. In
      horizontal position of the phase-encoding parameter, minimisation of the chemical
      shift artifact, mainly in the ventro-lateral areas, was accomplished. MRI
      measurements of the articular cartilage widths showed significant correlations (p
      < 0.001) with the corresponding anatomic sections. At the same time the T1 3
      dimensional gradient-echo sequence of the lateral femoral head with r = 0.94
      showed the lowest deviations of the measurements. It was possible with MR imaging
      to distinguish four cartilage qualities. CONCLUSIONS: Using these MR
      examinations, an improved imaging of early stage arthrotic cartilage defects is
      possible, and the status of the arthrotic hip cartilage with regard to
      intertrochanteric osteotomy can also be assessed.

PMID- 7579220
TI  - [The MR tomography of avascular necrosis of bone: the primary findings and the
      follow-up observations after core decompression].
AB  - PURPOSE: To assess the signal changes of avascular bone necrosis after core
      decompression. PATIENTS AND METHODS: 17 patients with avascular epiphyseal
      necrosis were examined by MRI using T1-weighted spin echo sequences before and
      after gadopentetate dimeglumine application, T2-weighted spin echo sequences and
      in some patients with fat-saturated 2D gradient echo sequences up to 22 months
      after core decompression. RESULTS: All patients but one recovered from symptoms
      after core decompression. Although the signal morphology of the necrotic area
      remained unchanged in the majority of the cases, a decrease of the joint effusion
      was observed as well as an ongoing signal increase after gadopentetate
      dimeglumine application. The last examinations displayed similar signal
      characteristics as on the preoperative scans; however, a reduction of the
      necrotic zone became evident. CONCLUSIONS: The decrease of joint effusion
      indicates successful core decompression, while a persistent signal increase after
      gadopentetate dimeglumine application reflects the viability of the necrotic area
      as well as an ongoing healing process.

PMID- 7579221
TI  - [The physician's duty to inform in interventional radiological therapeutic
      procedures].
AB  - PURPOSE: Interventional radiological procedures have important legal
      implications. The importance of informing the patient ("informed consent") before
      such procedures is examined in the light of German legal cases. MATERIAL AND
      METHODS: The German legal literature is reviewed and recent judgments of the
      Courts are cited. RESULTS: No all-embracing rules can be obtained from the
      judgments of the German Courts. Mostly one is dealing with individual judgments
      which can help in a general sense. The patient should be informed well before
      elective invasive procedures ("informed consent") and the amount of detailed
      information which is requested to be given to the patient appears to be
      increasing. Reversal of this trend in the future is unlikely. DISCUSSION: These
      judgments are of immediate significance for any radiologist who carries out
      interventional radiological procedures. In the case of complicated techniques the
      patient should be informed at the time of admission and a definite date for the
      procedure should be set. Explanations given on the evening before the procedure
      are deemed to be too late, unless there are exceptional circumstances. Where new
      forms of therapy are attempted, the information should be even more detailed. In
      particular it is necessary to stress the experimental nature of the procedure.

PMID- 7579223
TI  - [The diagnosis of acute pulmonary embolism: a comparison between spiral CT and
      DSA in an animal experiment].
AB  - PURPOSE: The value of helical computed tomography (CT) for diagnosis of acute
      pulmonary embolism was assessed and compared with digital subtraction angiography
      (DSA) as a reference method. MATERIAL AND METHODS: In 11 dogs, lobar, segmental,
      and subsegmental occlusions of the pulmonary arteries were produced. Subsequent
      to selective pulmonary angiography, the animals were examined with contrast
      enhanced helical CT. RESULTS: In the main and lobar pulmonary arteries there was
      a complete correlation between CT and DSA in documentation of total and partial
      embolic occlusions. Identification of segmental and subsegmental pulmonary emboli
      by CT required a second run with optimized parameters in 7 of 11 cases.
      Nevertheless, 18% of the peripheral arteries could not be classified. CONCLUSION:
      Helical CT as less invasive modality is competitive with DSA in demonstration of
      central pulmonary emboli. However, CT imaging of peripheral pulmonary emboli
      requires optimal bolus timing.

PMID- 7579222
TI  - [The reduction of the extent of vascular lesions during angioplasty by the use of
      a sheath].
AB  - PURPOSE: To document the protection of the vessel using an introducer sheath.
      MATERIAL AND METHODS: In eleven in situ specimens we compared in the inguinal
      vessel the macroscopic and histologic trauma to the vascular wall during
      antegrade percutaneous balloon dilatation either without or with a sheath.
      RESULTS: Significant differences we observed regarding both the puncture site
      configuration and the puncture hole border, which were evaluated macroscopically.
      During the histological assessment we found only small intimal trauma in the
      puncture track in the group where a sheath had been used. Severe intimal damages
      and the media showed tears if no sheath had been used (100/36% vs. 0/64%).
      CONCLUSION: It is evident that using a sheath during angioplasty reduces the risk
      of intimal damage and, consequently, of complications such as recurrent
      haematoma, stenosis at the puncture site or formation of aneurysms due to the
      puncture.

PMID- 7579225
TI  - [Computed tomography in acute rhabdomyolysis].

PMID- 7579224
TI  - [En-plaque meningioma as a rare cause of an osteosclerotic bone tumor of the
      frontal bone].

PMID- 7579226
TI  - [The manifestation of subcutaneous sarcoidosis in the area of the breast].

PMID- 7579227
TI  - [Cystic lymphangioma, lymphangiomatosis].

PMID- 7579228
TI  - [Angiosarcoma of the aorta--a case report].

PMID- 7579229
TI  - [Opening of the left V. spermatica interna into the left V. suprarenalis].

PMID- 7579230
TI  - Peritoneographic diagnosis of perineal enterocele after hysterectomy.

PMID- 7579231
TI  - [Polyploidy in the myocardium. Compensatory reserve of the heart].

PMID- 7579232
TI  - [Mice selected on the basis of low weight are more selective to the convulsant
      effect of pentylenetetrazole].

PMID- 7579235
TI  - [Differences in spinal dorsal horn neuronal activity in rats developing and not
      developing a pain syndrome after cutting the sciatic nerve].

PMID- 7579233
TI  - [Proliferation of capillary endothelium in the primary plexus of the hypothalamo
      hypophyseal portal circulatory system during rat ontogenesis].

PMID- 7579236
TI  - [Dependence between the baroreceptor reflex and the variability of arterial
      pressure and period of cardiac contraction in rats in arterial hypertension].

PMID- 7579234
TI  - [The effect of vagotomy on recurrent retardation of pancreatic secretion].

PMID- 7579237
TI  - [Reaction of pulmonary phagocytes after partial hepatectomy].

PMID- 7579238
TI  - [The protective effect of phosphatidylcholine liposomes in hemorrhagic shock in
      cats].

PMID- 7579240
TI  - [Platelet aggregation inhibition due to sodium hypochlorite. The effect of blood
      plasma components].

PMID- 7579239
TI  - [The effect of prophylactic administration of pentoxifylline (trental) on
      development of a neuropathic pain syndrome and microcirculatory disorders caused
      by it].

PMID- 7579241
TI  - [A probucol analog protects lipoproteins from oxidation better than does
      probucol].

PMID- 7579242
TI  - [The level of volatile fatty acids in saliva as an indicator of the status of the
      human oropharyngeal epithelium--normal microflora].

PMID- 7579243
TI  - [Decrease in atherogenicity of blood serum in vitro under the effect of
      polyunsaturated phosphatidylcholine micelles].

PMID- 7579244
TI  - [A comparative study of the pharmacologic effects of combined use of strophanthin
      with certain antiadrenergic substances].

PMID- 7579245
TI  - [Inhibition effect of C-reactive protein on the hemolytic activity of
      streptolysin O. Comparison of conformational variants].

PMID- 7579247
TI  - [The effect of amiridine and tacrine on reversible capture of neuromediators in
      experimental memory disorders].

PMID- 7579248
TI  - [Antimotion-sickness effect of nooglutil and its neuronal mechanism].

PMID- 7579249
TI  - [Structural changes in rat erythrocytes due to phosphacol poisoning].

PMID- 7579250
TI  - [Retardation of an experimental epileptogenic focus in the rat hippocampus by
      kynurenic acid].

PMID- 7579246
TI  - [Analysis of the effect of anapriline on circulatory system function].

PMID- 7579251
TI  - [Induced activation of peripheral blood mononuclear cells and neutrophils in
      recipients of allogeneic kidneys].

PMID- 7579252
TI  - [Immunization with neuromediators (serotonin, dopamine, noradrenaline) conjugated
      with a protein suppresses the morphine abstinence syndrome].

PMID- 7579255
TI  - [Study of chronobiological parameters of pain sensitivity in rats and mice].

PMID- 7579256
TI  - [Daily dynamics of the duration of hexenal narcosis in experimental hepatosis].

PMID- 7579253
TI  - [A myelopeptide (bivalfor), possessing antitumor activity].

PMID- 7579257
TI  - [Quantitative characteristics of recycling tissue corneal receptors].

PMID- 7579254
TI  - [Analysis of extrachromosomal DNA from normal and neoplastic cells].

PMID- 7579258
TI  - [The effect of low doses of radiation on central organs of erythro- and
      lymphocytopoiesis in the human fetus].

PMID- 7579260
TI  - [Character of changes in the homeostasis system, established using laser
      correlation spectroscopy, as long-term consequences of radiation exposure].

PMID- 7579259
TI  - [Transposition of great vessels with a defect in the interventricular wall and
      high pulmonary hypertension. Hemodynamics and results of correction].

PMID- 7579261
TI  - [Multiple modifications of low density lipoproteins in blood of patients with
      atherosclerosis].

PMID- 7579263
TI  - [The sympathetic nervous system does not participate in developing vagotomic
      tachycardia].

PMID- 7579262
TI  - [An invertor mechanism of the effect of insulin on the myocardiocyte cell
      membrane in animals of different ages].

PMID- 7579267
TI  - [Enzymatic composition of lymph from animals of different age groups during
      fever].

PMID- 7579266
TI  - [Phosphoinositide response and change in free radical oxidation in catecholamine
      cardionecrosis in rats].

PMID- 7579268
TI  - [Effect of methyluracil and oxymethacil on free radical oxidation in model
      systems].

PMID- 7579265
TI  - [Effect of substance P on changes in neurological status and behavioral reactions
      observed during long-term cerebral ischemia in rats with varying types of
      behavior].

PMID- 7579264
TI  - [The effect of preliminary gamma-irradiation of rats on the character of vascular
      tone changes upon intravenous administration of N. meningitidis
      lipopolysaccharide].

PMID- 7579269
TI  - [Activity of NO-synthase and generation of active forms of oxygen in sections of
      the aged rat brain: relationship with individual behavior].

PMID- 7579270
TI  - [Recordation of NADPH oxidation as a way to evaluate NO-synthase activity].

PMID- 7579271
TI  - [Biochemical mechanisms of hereditary cardiomyopathy development in W/SSM rats].

PMID- 7579272
TI  - [Protein-bound lipids in human low density lipoproteins].

PMID- 7579273
TI  - [Change in rat peripheral blood lymphocyte mitochondrial respiratory chain
      enzymes after exposure to ionizing radiation].

PMID- 7579274
TI  - [Effect of melipramine on the development of an experimental depressive syndrome
      in rats, caused by systemic administration of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)].

PMID- 7579275
TI  - [Change in the non-specific anti-infection resistance of the body exposed to
      cholinergic stimulation].

PMID- 7579276
TI  - [The effect of thymoptin on development of a conditioned passive avoidance
      reaction in 18-month old and castrated rats].

PMID- 7579278
TI  - [The role of ultrastructural changes of suckling rabbit lungs in pathogenesis of
      experimental cholera].

PMID- 7579277
TI  - [The effect of chitosan on biological properties of gram-negative bacterial
      endotoxins].

PMID- 7579279
TI  - [The significance of reproductive hormones in regulating production of
      prostaglandin F2alpha by immunocompetent cells].

PMID- 7579280
TI  - [Characteristics of anti-tumor activity of normal bone marrow cells].

PMID- 7579282
TI  - [Morphological characteristics of tissues from developing and atresic human
      graafian follicles].

PMID- 7579283
TI  - [Localization of blood plasma immunoglobulins in rat autonomic nerve ganglia
      tissue].

PMID- 7579281
TI  - [Differential induction of natural suppressor activity of bone marrow cells in
      vitro by various types of tumors].

PMID- 7579284
TI  - [Immunocytochemical study to localize a scavenger receptor in human aorta smooth
      muscle cells].

PMID- 7579285
TI  - [Use of porin from the outer membrane of Yersinia pseudotuberculosis for
      serodiagnosis of pseudotuberculosis].

PMID- 7579286
TI  - [Antibody to Bacillus megaterium H. glycoprotein in pregnant women with a
      pathological course of pregnancy].

PMID- 7579287
TI  - [Decrease in adenylate cyclase sensitivity to sodium ions in lymphocytes of
      patients with arterial hypertension].

PMID- 7579288
TI  - [Comparative characteristics of the efficacy of cisplatin and carboplatin in
      relation to human primary ovarian cancer cells].

PMID- 7579289
TI  - [Morphology of an additional (pharyngeal) adenohypophysis and its
      interrelationship with pharyngeal tonsils in the human fetus].

PMID- 7579290
TI  - [Detection of STLV-1 integration in DNA extracted from formalin-fixed and
      paraffin-embedded material from M. arctoides by polymerase chain reaction].

PMID- 7579292
TI  - [Determination of glucose concentration in human blood serum using a microbial
      biosensor].

PMID- 7579294
TI  - Cat on a hot tin roof.

PMID- 7579291
TI  - [Proliferative activity of tumor cells as a prognostic factor in breast cancer].

PMID- 7579295
TI  - The ageing labour force.

PMID- 7579293
TI  - [A radiometric method for determining the effect of xenobiotics on murine bone
      marrow cell proliferation].

PMID- 7579296
TI  - Occupational injuries in Bahrain.
AB  - A study was conducted to show the problem of occupational injuries in Bahrain and
      try to highlight some solutions that may help to prevent or reduce workplace
      hazards. The data for occupational injuries between 1988 to 1991 from the social
      insurance records were reviewed and analysed. The data were summarized, grouped
      and tabulated according to age, sex, nationality, work place, type of injuries,
      cause and site of injury. Data were analysed statistically, frequencies were
      computed and results represented graphically. The study shows that there was a
      decline in the number of injuries in 1990 and 1991 due to a slow-down of economic
      activities in general in the Arabian Gulf region during the Gulf War. It also
      shows that Asian workers are at a high risk of occupational injuries.

PMID- 7579297
TI  - Is a telephone helpline of value to the workplace smoker?
AB  - This paper reports the findings of the evaluation of a national smokers' helpline
      which was set up by British Telecom (BT) for its employees. The helpline formed
      part of a new comprehensive smoking policy for all BT staff. Over 1000 employees,
      more than 3.0% of all smokers, phoned the helpline during the first three months
      of its operation. Two-thirds of callers tried to quit smoking after calling the
      helpline, and a quarter were still successful three months later. One in six
      callers reduced the number of cigarettes that they smoked on working days. While
      the helpline and other cessation support services were evaluated positively by
      callers, it appears that helplines only appeal to a small minority of smokers.
      However, they do seem to be an effective mechanism for a nationwide company to
      identify those smokers who want support, and a useful means of centralizing the
      administration of support services. They are potentially a cost-effective option
      for larger employers.

PMID- 7579298
TI  - Health status and exposure of workers at a pilot brown coal liquefaction plant in
      Australia, 1985-1991.
AB  - In 1985, Brown Coal Liquefaction (Victoria) Pty Ltd (BCLV) commenced operation of
      a pilot plant that investigated the feasibility of producing oil from brown coal.
      The plant operated for five years. This study aimed to use exposure and health
      information routinely collected by the company to characterize various health
      parameters of the workforce and to investigate whether any adverse health
      measures were exposure-related. About 1680 persons were employed at some time or
      other by BCLV, and the primary study population consisted of 408 workers who had
      a medical examination at the end of employment and who consented to being in an
      epidemiological study. Reported photosensitivity was associated with higher
      cumulative skin exposure (RR = 1.85; 95% CI = 1.22-2.78), with an exposure
      response relationship of increasing risk with increasing skin exposure being
      suggested. There was no consistent evidence that chemical exposure at BCLV had
      any negative effect on the haematological, biochemical, endocrine or lung
      function of workers at the plant. However, the maximum follow-up period of less
      than eight years limits the ability of the study to detect any emerging chronic
      effects.

PMID- 7579299
TI  - The methodological problems of multinational epidemiological studies with
      particular reference to carbon black studies.
AB  - The reduction in the size of available populations within a single company or
      country has forced researchers to use multicentric and even multinational study
      designs. This paper describes an example of this approach by means of reviewing
      the published carbon black literature with specific regard to the epidemiological
      difficulties, the study design used in the multinational European carbon black
      study, and a discussion of the difficulties and weaknesses encountered. A number
      of solutions are proposed to counter the inherent drawbacks of this design, and
      it is felt that the advantages outweigh the disadvantages.

PMID- 7579300
TI  - Risk of physical assaults among student nurses.
AB  - This study was undertaken within two teaching hospitals (one general and one
      psychiatric) in a large health board. Its purpose was to compare the rates of
      physical assaults on student nurses with those on other grades of nursing staff,
      to explore the aetiological factors associated with attack, and to identify what
      preventive measures were in place and what support systems were available for
      affected staff. Data were collected from completed incident forms and from a semi
      structured questionnaire administered to the student nurses. The rate of reported
      assault was much higher in the psychiatric hospital than the general hospital,
      but the severity of the assault was greater in the general hospital. Age and
      height were not risk factors for assaults. The study showed inadequate training,
      under-reporting of incidents, poor utilization of occupational health departments
      and a lack of support for victims of physical assaults.

PMID- 7579301
TI  - Exposure to glycols and their renal effects in motor servicing workers.
AB  - Ten car mechanics frequently exposed to glycol-based cooling liquids were
      followed during a workshift. Airborne ethylene and propylene glycol
      concentrations in the car mechanics' environment were measured. The car mechanics
      gave urine samples after the workshift and their excretion of ethylene glycol,
      propylene glycol, oxalic acid, calcium and ammonia was analysed and compared to
      that of unexposed office workers. Urinary succinate dehydrogenase activity and
      glycosaminoglycans were also measured in both groups. Airborne ethylene and
      propylene glycol concentrations in the car mechanics' environment were
      negligible. Urinary ethylene glycol excretion in exposed workers was
      significantly higher than that in unexposed workers, but propylene glycol
      excretion was at the same levels as in controls. In the exposed group, the
      excretion of the end metabolite of ethylene glycol, oxalic acid (47 +/- 11
      mmol/mol creatinine, mean +/- SD, n = 10) differed slightly from that of controls
      (36 +/- 14 mmol/mol creatinine, mean +/- SD, n = 10). Urinary excretion of
      ammonia was higher among exposed workers than office workers. The excretion of
      calcium did not differ from that of controls. A marginally decreased urinary
      succinate dehydrogenase activity was found in the exposed men. The excretion of
      glycosaminoglycans was significantly lower in exposed workers. Therefore, it
      seems that ethylene glycol is absorbed by skin contact. The internal body burden
      is associated with oxaluria and increased ammoniagenesis typical of chronic
      acidosis.

PMID- 7579302
TI  - Epidemiological aspects of back pain: the incidence and prevalence of back pain
      in nurses compared to the general population.
AB  - Two studies using retrospective questionnaires were conducted to obtain
      epidemiological information from nursing personnel (n = 1134) and among an age-
      and gender-matched cross-section of the general population (n = 315). The point
      and annual prevalence of back pain did not differ between the two sample groups.
      Nurses demonstrated a greater annual incidence of back pain (14.7%, compared to
      11.5% in non-nurses). The point prevalence of back pain increased with age in
      both sample groups. Nurses considered patient-handling tasks instrumental in the
      onset of back pain symptoms. Comparison of results with those obtained from a
      similar study published in 1983 indicated an increase of almost 40% in the
      prevalence of back pain symptoms in nurses, although the linearity of the rise
      was not ascertained. The implementation of guidelines on the manual handling of
      loads has led to revised training procedures and these may have influenced the
      epidemiological findings.

PMID- 7579303
TI  - Multiple channels for occupational health services to small-scale enterprises in
      Japan.
AB  - This study was performed to clarify the characteristics of multiple channels for
      occupational health services (OHS) to small-scale enterprises (SSEs) in Japan
      employing less than 50 workers by reviewing relevant research papers. OHS were
      provided to SSEs by both government organizations and non-government
      organizations. Government organizations included the Japanese Industrial Safety &
      Health Association, regional occupational health centres, prefectural
      occupational health promotion centres, and other health centres. Non-government
      organizations were parent companies, occupational health organizations,
      hospitals, medical associations, trade associations and health insurance
      societies. The quality of OHS in terms of provision of health personnel and the
      nature of their services differed greatly between the organizations. Health care
      programmes were more popular than management of the work environment or working
      practices in OHS to SSEs. Few organizations provided comprehensive OHS to SSEs.
      At present, parent companies and occupational health organizations appear to
      provide the best OHS available to SSEs in Japan.

PMID- 7579306
TI  - Failure of diagnosis: a key indicator in quality assurance of tuberculosis
      control.

PMID- 7579305
TI  - Acute multiple mononeuropathy after accidental exposure to oven microwaves.
AB  - A patient accidentally exposed to oven microwaves developed an acute and severe
      dystrophy and sympathetic reflex of the right hand, a peripheral neuropathy of
      the digits of the left hand, and a sensory injury of the trigeminal nerve in the
      right side of the face. The physiopathological involvement in the injury of the
      peripheral nerve and the failure of analgesia with carbamazepine are emphasized.
      In this causalgia, relief from pain and modification of the autonomic disorders
      can be achieved by a sympathetic block.

PMID- 7579304
TI  - Management of sharps injuries and contamination incidents in health care workers:
      an audit in the Wessex and Oxford regions.
AB  - Fifteen NHS occupational health departments from the Wessex and Oxford regions
      took part in an audit of the management of sharps injuries and contamination
      incidents. Data were collected prospectively for a series of 1102 incidents
      notified over a nine-month period. The rates of notified incidents for each
      department ranged from 9 to 44 incidents per 1000 staff members per year. The
      proportion of injured employees who were naturally immune to hepatitis B or had
      completed a full course of vaccination against the infection ranged from 57 to
      83%, with the main shortfall occurring in ancillary workers. Some departments
      rarely stored source serum, while others did so in the majority of cases. The
      proportion of cases where the injured person was known to have had hepatitis B
      antibody levels > 100 IU/l within the past 12 months, or underwent immediate
      antibody assessment or had an immediate vaccination against hepatitis B varied
      from 26 to 97%, with a median of 68%. On the basis of these findings, the audit
      group has set targets against which performance will be re-assessed in a follow
      up exercise.

PMID- 7579307
TI  - Factors associated with extrapulmonary tuberculosis as an AIDS-defining disease
      in Europe. The Coordinators of AIDS surveillance in Austria, Belgium, France,
      Germany, Italy, Portugal, Switzerland, United Kingdom and the city of Amsterdam.
AB  - SETTING: Western Europe: 8 countries and the city of Amsterdam. OBJECTIVE: To
      identify factors associated with extrapulmonary tuberculosis (EPTB) at AIDS
      diagnosis among adult AIDS patients. DESIGN: The proportion of AIDS case
      diagnosed between January 1988 and June 1992 with EPTB was analysed by age,
      gender, year of diagnosis, country and HIV transmission category. Multiple
      logistic regression was performed separately for patients infected through
      heterosexual contact who were likely to originate from Africa or the Caribbean
      (heterosexual subgroup 1), and for other patients. RESULTS: The overall
      proportion with EPTB was 4.6% and remained stable between 1988 and 1992. It
      differed significantly by country (from 2.4% in the United Kingdom to 24.7% in
      Portugal) and by transmission category (2.7% among homo/bisexuals, 5.8% among
      injecting drug users, 13.6% among heterosexual subgroup 1). In multivariate
      analysis, the risk of EPTB was independently associated with younger age and male
      gender. Among patients other than from heterosexual subgroup 1, country and
      transmission category were also independent predictors of EPTB at AIDS diagnosis.
      CONCLUSION: The risk of presenting EPTB as an AIDS-defining disease is not
      homogeneous within Europe. Results suggest an increased risk of tuberculosis in
      specific groups of HIV-infected persons (persons originating from sub-Saharan
      Africa, injecting drug users) and a potential role of recent Mycobacterium
      tuberculosis infection among younger patients.

PMID- 7579308
TI  - Impact of the change from an injectable to a fully oral regimen on patient
      adherence to ambulatory tuberculosis treatment in Dar es Salaam, Tanzania.
AB  - OBJECTIVE: To measure the impact on patient adherence to directly observed
      ambulatory tuberculosis treatment substituting an all-oral treatment regimen for
      a regimen containing streptomycin. METHODS: The expected and observed attendance
      of patients during the intensive phase of anti-tuberculosis treatment was
      measured daily at two out-patient clinics in Dar es Salaam. During the
      observation period, treatment was changed from a regimen containing streptomycin
      to an all-oral regimen, and attendance proportions were compared for the three
      periods during which patients always, sometimes or never received streptomycin
      during the intensive phase of treatment. RESULTS: In Kinondoni, an average of 98
      patients was expected every day, in Ilala 127. No significant difference was
      observed in attendance in Kinondoni between periods when patients always (median
      attendance 95.9%) and never (median 95.7%) received streptomycin injections as
      part of their intensive phase treatment for tuberculosis. In Ilala, no difference
      was noted in attendance between the period in which patients received
      streptomycin for at least part of their treatment (median 91.3%) and the period
      when ethambutol had fully replaced streptomycin (median 91.8%). CONCLUSIONS: In
      these two districts of Dar es Salaam, patient adherence to a completely oral
      treatment regimen was indistinguishable from that to a streptomycin-containing
      regimen. Given the potential of iatrogenic transmission of HIV and the advantages
      in reduced staff time and drug costs, the results clearly justify the replacement
      of streptomycin with ethambutol in Tanzania for new patients receiving an
      ambulatory rifampicin-containing regimen.

PMID- 7579309
TI  - The effect of age on the presentation of patients with tuberculosis.
AB  - OBJECTIVE: To study the differences in presentation of young and elderly patients
      with tuberculosis (TB). DESIGN: Between January 1991 and December 1992 all
      patients with TB diagnosed at the Department of Medicine, Prince of Wales
      Hospital, were recruited into the study. The following data were collected: body
      weight, coexisting medical problems, presenting symptoms, radiographic
      appearance, sputum results for acid-fast bacilli and peripheral blood
      biochemistry. The patients were divided into young ( < 65 years) and elderly ( >
      or = 65 years) age groups and differences in presentation of the 2 groups were
      analysed. RESULTS: There were 78 young and 94 elderly patients with TB. The
      elderly patients had lower body weight, less haemoptysis but more non-specific
      complaints (25% vs 1%, P = 0.001). The chest radiographs in the elderly patients
      were less likely to have upper lobe infiltration (9% vs 37%, P = 0.0002) but more
      commonly had extensive infiltration of both lungs (17% vs 2%, P = 0.014). The
      only biochemical abnormality that was more common in the elderly was a low serum
      albumin level (64% vs 45%, P < 0.05). CONCLUSION: Elderly patients with TB are
      more likely to present with non-specific complaints and atypical radiographic
      appearance. A high index of suspicion and prompt investigations in elderly
      patients may allow for earlier diagnosis and treatment of TB.

PMID- 7579310
TI  - Value of bronchoalveolar lavage and gastric lavage in the diagnosis of pulmonary
      tuberculosis in children.
AB  - OBJECTIVE: The aim of our study was to find out if bronchoalveolar lavage (BAL)
      would be better than gastric lavage for the isolation of Mycobacterium
      tuberculosis from pediatric patients with suspected pulmonary tuberculosis.
      DESIGN: 50 children with suspected pulmonary tuberculosis at a mean age of 5.1
      years (range 7 months to 12 years) were studied. Early morning gastric lavage was
      collected. Flexible bronchoscopy and bronchoalveolar lavage was performed under
      local anaesthesia after obtaining informed consent from the parents. The BAL
      fluid and gastric lavage specimens were subjected to smear examination for acid
      fast bacilli (AFB) and culture for mycobacteria using established methods.
      RESULTS: Of the 50 cases, M. tuberculosis was grown in 6 BAL samples (12%) and 16
      gastric lavage samples (32%) making a total of 17 culture proven cases (34%). Out
      of the 6 BAL positive cases, gastric lavage was also positive in 5 cases.
      CONCLUSION: We conclude that gastric lavage is better than BAL for bacteriologic
      confirmation of pulmonary tuberculosis in children. The overall bacteriologic
      yield combining both procedures was 34% while gastric lavage alone was positive
      in 32% of the cases.

PMID- 7579311
TI  - Atypical mycobacteria in extrapulmonary disease among children. Incidence in
      Sweden from 1969 to 1990, related to changing BCG-vaccination coverage.
AB  - SETTING: In April 1975, the general BCG vaccination of newborns in Sweden was
      replaced by selective vaccination of groups at increased risk of tuberculosis.
      OBJECTIVE: To relate the incidence of atypical mycobacterial disease in children
      to BCG vaccination. DESIGN: A nationwide survey in Sweden during the period 1969
      90 disclosed 390 children under 15 years of age with bacteriologically confirmed
      atypical mycobacteria from extrapulmonary lesions. RESULTS: The average, annual
      incidence of atypical mycobacterial disease per 100,000 children under 5 years of
      age increased from 0.06 during the period 1969-74 to a maximum level of 5.7
      during 1981-85. Among the cohorts born in Sweden in the period 1975-85, the
      cumulative incidence rate before 5 years of age was estimated at 26.8 per 100,000
      non-BCG-vaccinated children and at 4.6 among those BCG-vaccinated, ratio 5.9 (95%
      confidence limits 1.6, 48.5). Mycobacterium avium-intracellulare was found in
      83%. Disseminated, fatal disease developed in 3 children. The remaining ones
      suffered from local infections, most often lymph-node or soft-tissue lesions. The
      observed incidence of bacteriologically confirmed diagnosis was estimated to
      represent approximately 40% of the 'true' number, if patients with diagnosis
      based on histological, clinical and epidemiological findings only were included.
      CONCLUSION: The present study indicates that BCG vaccination plays a role in
      protection against localized disease caused by atypical mycobacteria in children.

PMID- 7579313
TI  - Dental units: an environmental study of sources of potentially pathogenic
      mycobacteria.
AB  - SETTING: Infections caused by non-tuberculous mycobacteria (NTM) are generally
      thought to be acquired from environmental sources. However, little is known about
      the situations in which transmission occurs. OBJECTIVE: In an attempt to identify
      situations of relevant contact with NTM we investigated the water to which
      patients are exposed during dental treatment. DESIGN: The concentration and
      species of NTM were determined in 43 cooling and spray water samples from 21
      dental units in ten offices. In addition, mycobacterial colonization of 16
      biofilm samples from the waterlines of two dental units was investigated.
      RESULTS: The mean NTM concentration in the water samples was 365 colony-forming
      units (cfu) per mL, exceeding the mean drinking water concentration by a factor
      of almost 400. In the biofilm samples the mean NTM density amounted to 1165
      cfu/cm2. The species identified included Mycobacterium gordonae, M. flavescens,
      M. chelonae, 'M. chelonae-like organism' and M. simiae. CONCLUSION: High numbers
      of NTM may be swallowed, inhaled or inoculated into oral wounds during dental
      treatment, possibly resulting in colonization, sensitization or infection.
      Mycobacterial proliferation in biofilms forming within dental units may explain
      the extent of NTM contamination of dental spray and cooling water.

PMID- 7579312
TI  - A controlled clinical trial of short-course chemotherapy for tuberculoma of the
      brain.
AB  - OBJECTIVE: The efficacy of a short-course regimen in the treatment of brain
      tuberculoma and computerised tomography (CT) scan appearance before, during and
      after antituberculosis treatment was studied in a controlled clinical trial.
      DESIGN: Patients aged over 5 years with tuberculoma of the brain diagnosed by CT
      scan were randomly allocated to one of the following 2 regimens: Regimen 1:
      rifampicin, isoniazid and pyrazinamide daily for an initial 3 months followed by
      rifampicin and isoniazid twice-weekly for 6 months. Regimen 2: rifampicin,
      isoniazid and pyrazinamide thrice-weekly for an initial 3 months followed by
      rifampicin and isoniazid twice-weekly for 6 months. The patients were followed
      intensively for 2 years from the start of treatment. RESULTS: Of the 108 patients
      analysed (regimen 1: 56, regimen 2: 52), at the end of treatment clinical status
      was normal in 91% in regimen 1 and 88% in regimen 2. Of the 91 patients with scan
      assessments, CT scan lesions disappeared at 24 months in 77% of 47 patients in
      regimen 1 and 80% of 44 in regimen 2, and in both groups 88% of the patients were
      clinically normal. None had relapses requiring treatment. CONCLUSIONS: Short
      course regimens of 9 months' duration are effective in the treatment of
      tuberculoma of the brain; clinical recovery was faster than scan clearance.

PMID- 7579314
TI  - Limited variation of DNA fingerprints (IS6110 and IS1081) in Korean strains of
      Mycobacterium tuberculosis.
AB  - OBJECTIVE: To establish the usefulness of DNA fingerprinting for the epidemiology
      of Mycobacterium tuberculosis isolated from Korean tuberculosis patients.
      METHODS: Comparison of restriction fragment length polymorphism (RFLP) patterns
      produced by southern hybridization of PvuII-digested chromosomal DNA. RESULTS:
      IS6110-associated banding patterns of 41 isolates varied considerably, containing
      1-13 copies. The RFLP pattern of the epidemiologically related M. tuberculosis
      isolates was identical in 8 of 10 groups of close contact patients. No noticeable
      differences in RFLP were observed between drug-sensitive and drug-resistant
      isolates. IS1081-containing restriction fragment analysis of 52 isolates showed 6
      different banding patterns, and the C type was found dominant in Korea.
      Identification of G type M. tuberculosis, which has a 8.0 kb IS1081-containing
      PvuII fragment, is unusual because it has been observed only in M. bovis BCG so
      far. CONCLUSIONS: IS6110 was a very useful tool for tracing the transmission
      route of tuberculosis; IS1081 was also useful for subdividing M. tuberculosis
      into several groups.

PMID- 7579315
TI  - Identification of Mycobacterium intracellulare by a polymerase chain reaction
      using species-specific primers.
AB  - SETTING: The polymerase chain reaction (PCR) is a rapid and specific method used
      to amplify a certain DNA fragment. It is applicable to rapid diagnosis of
      mycobacterial infections. By use of species-specific primers, it is possible to
      identify mycobacteria by PCR. In this study, a newly constructed primer was
      tested for specificity for Mycobacterium intracellulare in the PCR. OBJECTIVE: M.
      intracellulare is one of the most frequently found bacteria in opportunistic
      infection in AIDS, and rapid identification of this species is important. The
      purpose of this study was to construct a primer specific to this species as a
      suitable tool for identification. DESIGN: PCR products of M. tuberculosis and M.
      intracellulare, obtained by using the primers YNP-1 and YNP-2, were sequenced and
      compared. They showed a difference in the base sequences. A sequence unique to M.
      intracellulare was used as the primer specific to this species. Various
      mycobacterial and non-mycobacterial DNAs were used as the primer specific to this
      species. Various mycobacterial and non-mycobacterial DNAs were used as the
      template to evaluate the specificity of the newly constructed primers, YNP-7 and
      YNP-8. Sputum samples were also examined by PCR using the primers. RESULTS: In
      total 25 species of culture mycobacterial and non-mycobacterial strains and 76
      sputum samples were tested by PCR. Only M. intracellulare DNA was amplified with
      PCR using the primers YNP-7/8. CONCLUSION: The specificity of the newly
      constructed primers for M. intracellulare was confirmed.

PMID- 7579316
TI  - Establishment and evaluation of a multiplex polymerase chain reaction for
      detection of mycobacteria and specific identification of Mycobacterium
      tuberculosis complex.
AB  - OBJECTIVE: To establish a multiplex polymerase chain reaction for detection of
      mycobacteria and specific identification of Mycobacterium tuberculosis complex
      and to evaluate the test in the diagnosis of tuberculosis. DESIGN: Three sets of
      primers were used to amplify 383 bp, 240 bp and 131 bp DNA fragments from the
      genes encoding the 65 kDa, MPB64 and the 19 kDa proteins of M. tuberculosis in a
      single reaction tube. Reaction conditions were optimized with respect to the
      requirement of DMSO, concentration of MgCl2, annealing and denaturation
      temperatures and number of amplification cycles. Inhibitory activity in clinical
      samples was identified by amplifying a 500 bp DNA fragment of the phage lambda
      along with the mycobacterial targets within the same reaction tube. The multiplex
      PCR was evaluated in differentiating M. tuberculosis complex from other
      mycobacteria and in the diagnosis of tuberculosis by testing clinical specimens.
      RESULTS: Amplification of the 383 bp DNA fragments was specific to the genus
      Mycobacterium. The 240 bp DNA fragment was amplified from M. tuberculosis complex
      and M. fortuitum and the 131 bp DNA fragment was amplified from the mycobacteria
      of M. tuberculosis complex and M. scrofulaceum. All the three bands were
      amplified only from M. tuberculosis complex. Applicability of the multiplex PCR
      is demonstrated in differentiating M. tuberculosis complex from other
      mycobacteria by using standard strains and clinical isolates. The multiplex PCR
      was also useful in the detection of inhibitory activity and in the identification
      of M. tuberculosis complex directly in clinical samples. CONCLUSION: The
      multiplex PCR established in this study could differentiate M. tuberculosis
      complex from other mycobacteria. This test may also be helpful in the early and
      specific diagnosis of tuberculosis.

PMID- 7579317
TI  - Management of hemoptysis in a Third World city hospital: a retrospective study.
AB  - BACKGROUND: Massive hemoptysis (defined as blood loss greater than 600 ml/24h) is
      said to have a fatal outcome in up to 85% of patients when managed only
      medically. METHODS: A retrospective patient chart study was undertaken to analyse
      underlying pathology, management and outcome of hemoptysis patients in a hospital
      with no thoracic surgical, bronchoscopic or embolisation facilities. RESULTS: 63
      patients were admitted for hemoptysis during a 2.5 year study period.
      Tuberculosis and sequelae of previous tuberculosis accounted for 65% of the
      cases. The patients with expectoration of more than 600 ml/24h had a shorter
      duration of hemoptysis (P = 0.033) and more often a history of tuberculosis (P =
      0.023). The mortality rate was 6% (4/63 patients). Recurrent bleeding was not
      frequent (11%) and never severe enough for admission. CONCLUSIONS: Hemoptysis in
      a Third World city hospital is mainly caused by infectious disease. Under the
      above-mentioned circumstances, in view of a low mortality and recurrence rate,
      conservative treatment of hemoptysis in in-patients seems justified.

PMID- 7579318
TI  - Tuberculosis in the autopsy material: analysis of 1500 autopsies performed
      between 1972 and 1991 in the Institute of Tuberculosis and Chest Diseases,
      Warsaw, Poland.
AB  - SETTING: The present study is based on 1500 autopsies done in the Institute of
      Tuberculosis and Chest Diseases Warsaw, Poland during the years 1972-81 and 1982
      91. OBJECTIVE: To assess the correctness of tuberculosis diagnosis before death
      in the above mentioned time periods. DESIGN: The autopsy reports were examined
      for the diagnosis of active tuberculosis proved by microscopy. The form and
      localisation of tuberculosis was assessed. The postmortem diagnosis was compared
      with clinical diagnosis. In those cases in which tuberculosis was not recognised
      before death the possible causes of this failure were analyzed. RESULTS: Active
      tuberculosis was found in 119 cases, 7.9% of all autopsies. It was localised in
      the lungs exclusively in 72 cases, in lungs and in extrapulmonary sites in 45 and
      in extrapulmonary sites only in 2. The frequency of active tuberculosis was the
      same for the two periods under evaluation. Tuberculosis was however not
      recognised before death in a much higher proportion of cases in 1982-92 (54%)
      than in 1972-81 (24%). The main cause of diagnostic failure was connected with
      atypical localisation of lesions on chest X-ray and with dissemination outside
      the lungs. Previous tuberculosis was a factor which facilitated the diagnosis of
      tuberculosis. CONCLUSIONS: In parallel with the decline of tuberculosis incidence
      in Poland, many doctors lack experience in diagnosing this disease, especially in
      cases with atypical X-ray presentation and with extrapulmonary localisation. This
      may lead to late or even very late diagnosis and have a significant impact on the
      epidemiological situation.

PMID- 7579319
TI  - Feasibility of involving literate tribal youths in tuberculosis case-finding in a
      tribal area in Tamil Nadu.
AB  - SETTING: Tribal area in South India with a population of 96,000, where the
      tuberculosis case-finding activity was very poor. OBJECTIVES: To investigate the
      feasibility of (1) involving literate (who can read and write) tribal youth
      volunteers for detecting cases of pulmonary tuberculosis (PT) in their respective
      hamlets; and (2) antituberculosis drug delivery to sputum-positive patients at
      their homes by village health nurses (VHNs). DESIGN: One volunteer from each of
      61 hamlets was selected and trained in the detection of subjects with chest
      symptoms, sputum collection and transportation to the Primary Health Centre for
      smear examination. All smear-positive patients were treated with 2RHZ/6TH and the
      drugs were supplied by VHNs fortnightly at their homes. RESULTS: During a period
      of 1 year (1992-93), the total population screened was 9383 persons; of these
      5755 were aged 15 years and above. A total of 338 symptomatic subjects were
      identified; 12 sputum-positive cases were detected and started on treatment.
      Antituberculosis drugs were supplied by VHNs to patients for the first 9 months
      of the study and by literate youths for the next 3 months. Spot drug checks
      revealed that 11 of the 12 patients were regular in drug consumption. CONCLUSION:
      It is feasible to train literate tribal youth volunteers within a short time to
      detect subjects with chest symptoms in the community and thereby cases of
      pulmonary tuberculosis. They can serve as an excellent model for community
      participation in difficult areas.

PMID- 7579320
TI  - Prepacked kits for diagnosis and treatment of tuberculosis in former Yugoslavia.
AB  - SETTING: After the outbreak of armed conflicts in the republics of former
      Yugoslavia in 1991, basic health services deteriorated and shortages of essential
      medical supplies occurred. The World Health Organization (WHO) has taken part in
      emergency relief operations in the area since July 1992. There was a growing
      concern that poor living conditions and shortages of supplies could rapidly
      increase the tuberculosis problem. OBJECTIVE: To provide essential supplies, WHO
      included support of tuberculosis control in the emergency relief operations for
      former Yugoslavia. DESIGN: WHO designed a prepacked kit with anti-tuberculosis
      drugs and material for sputum smear examination for use in combination with
      policy recommendations and a treatment protocol. RESULTS: The initial
      distribution of the kits was completed by the end of April 1994. Medium term
      support from May 1994 onwards has included continued distribution of kits,
      together with assistance in adjusting tuberculosis control programmes according
      to the recommended WHO policy package. CONCLUSION: Support of tuberculosis
      control with essential supplies and strictly focusing on priority measures is
      proposed as the most adequate strategy, when dealing with a developed country
      dependent on humanitarian assistance.

PMID- 7579321
TI  - [Treatment of pleural tuberculosis with a short 4-month regimen: preliminary
      results].
AB  - The aim of this prospective study was to evaluate the results of a four-month
      regimen (2HRZ/2HR) in the treatment of isolated tuberculous pleurisy with
      effusion. It included 68 patients presenting with histologically confirmed
      tuberculous pleurisy treated with 2HRZ/2HR, physiotherapy and aspiration of the
      pleura. Patients were seen every 2 months during treatment, and then 1, 3, 4, 6,
      12, and 24 months after the end of treatment. Preliminary results show a
      favourable response in 58 patients (85%) and minimal pleural thickening in 10
      patients. There were no failures, no relapses nor any extrapleural dissemination
      after a follow-up period of on average 20 months. These encouraging results need
      to be evaluated in a long-term study.

PMID- 7579322
TI  - Tumor necrosis factor-alpha (TNF-alpha) in pleural fluids.
AB  - Our study was undertaken to investigate the role of tumor necrosis factor-alpha
      (TNF-alpha) at the site of disease activity in tuberculous pleuritis (TP).
      Concentrations of TNF-alpha were measured directly by radioimmunoassay (RIA) in
      the pleural fluid (PF) and plasma (P) of patients with TP (n = 14), malignant
      effusions (n = 18) and transudates (n = 7). Among these three groups mean plasma
      levels of TNF-alpha were not statistically significant (P > 0.05), but in the TP
      group mean levels of TNF-alpha in PF were significantly higher than in the cancer
      and transudate groups (P < 0.001), and there was no significant difference
      between the cancer and transudate groups (P > 0.05). These results may indicate a
      local synthesis of TNF-alpha by cells within the pleural cavity in this disease.

PMID- 7579323
TI  - BCG test: 100% sensitive and 100% specific?

PMID- 7579324
TI  - Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial
      meningitis.

PMID- 7579325
TI  - Ethambutol versus streptomycin during the hospitalized intensive phase of
      tuberculosis treatment in Benin.

PMID- 7579326
TI  - The epidemiology of Mycobacterium bovis infections in animals and man: a review.
AB  - Tuberculosis is primarily a respiratory disease and transmission of infection
      within and between species is mainly by the airborne route. Mycobacterium bovis,
      the cause of bovine-type tuberculosis, has an exceptionally wide host range.
      Susceptible species include cattle, humans, non-human primates, goats, cats dogs,
      pigs, buffalo, badgers, possums, deer and bison. Many susceptible species,
      including man, are spillover hosts in which infection is not self-maintaining. In
      countries where there is transmission of infection from endemically infected
      wildlife populations to cattle or other farmed animals, eradication is not
      feasible and control measures must be applied indefinitely. Possible methods of
      limiting spread of infection from wildlife to cattle including the use of
      vaccines are outlined. The usefulness of DNA fingerprinting of M. bovis strains
      as an epidemiological tool and of BCG vaccination of humans and cattle as a
      control measure are reviewed. The factors determining susceptibility to infection
      and clinical disease, and the infectiousness of infected hosts and transmission
      of infection, are detailed. Reports of the epidemiology of M. bovis infections in
      man and a variety of animal species are reviewed. M. bovis infection was
      recognised as a major public health problem when this organism was transmitted to
      man via milk from infected cows. The introduction of pasteurization helped
      eliminate this problem. Those occupational groups working with M. bovis infected
      cattle or deer, on the farm or in the slaughter house, are more likely to develop
      pulmonary disease than alimentary disease. In recent years, tuberculosis in
      farmed cervidae has become a disease of economic as well as public health
      importance in several countries. Nowadays, the human immunodeficiency virus (HIV)
      is associated with a greatly increased risk of overt disease in humans infected
      with Myobacterium tuberculosis. It is believed this increased risk also occurs in
      the case of M. bovis infections in humans.

PMID- 7579327
TI  - Molecular mechanisms of human T-cell leukemia/lymphotropic virus type I
      infection.

PMID- 7579328
TI  - The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro.
AB  - MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of
      myeloid differentiation. The MZF-1 protein contains 13 C2H2 zinc fingers arranged
      in bipartite DNA binding domains containing zinc fingers through 4 and, in the
      carboxy-terminus, 5 through 13. We previously identified the DNA consensus
      binding site recognized by the two DNA binding domains. To assess the
      transcription regulatory function of MZF-1, the full-length MZF-1 coding region
      was fused to the DNA binding domain of the yeast transactivator GAL4. The
      expression vector was cotransfected with the chloramphenicol acetyl transferase
      (CAT) reporter gene regulated by the thymidine kinase promoter containing GAL4
      DNA binding sites into NIH 3T3, 293, K562, and Jurkat cell lines. MZF-1 represses
      CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell
      lines NIH 3T3 and 293. In contrast, MZF-1 activates CAT reporter gene expression
      in the hematopoietic cell lines K562 and Jurkat. The MZF-1 binding sites are
      present in the promoters of several genes expressed during myeloid
      differentiation, including the CD34 promoter. MZF-1 transcriptional regulation of
      this physiologically relevant promoter was assessed in both hematopoietic and
      nonhematopoietic cell lines. Recombinant MZF-1 protein specifically binds to the
      consensus binding sites in the CD34 promoter in mobility shift assays. MZF-1
      expression vectors were cotransfected with the luciferase reporter plasmids
      regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell
      lines. As with the heterologous DNA binding domain, MZF-1 represses reporter gene
      expression in nonhematopoietic cell lines and activates expression in
      hematopoietic cell lines. Activation of CD34 expression in hematopoietic cell
      lines is dependent on the presence of intact MZF-1 binding sites. The cell type
      specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue
      specific regulators/adapters or differential MZF-1 modifications that determine
      MZF-1 transcriptional regulatory function.

PMID- 7579329
TI  - High prevalence of nonsense, frame shift, and splice-site mutations in 16
      patients with full-blown Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is a fully penetrant X-linked recessive disorder
      characterized by immunodeficiency, thrombocytopenia, and severe eczema. WAS is a
      life-threatening disease, with a poor quality of life and high mortality rate in
      childhood. The gene responsible for the disease has been localized to the
      proximal short arm of the X-chromosome and recently isolated through positional
      cloning and named WAS protein (WASP). We have characterized 17 WAS families. We
      have developed a rapid, nonradioactive screening protocol for identifying WASP
      gene alterations in genomic DNA. Our method allows simultaneous evaluation of
      single strand confirmation polymorphism and heteroduplex formation. We have
      identified 15 novel mutations that involve single basepair changes, or small
      insertions or deletions, all of which result in premature stop cordon, frame
      shift with secondary premature stop codon, or splice site defect. These studies
      document the considerable heterogeneity of the location of mutations in the WASP
      gene causing full-blown WAS and show the efficiency and rapidity of a screening
      approach for mutation identification in WAS that will be useful for carrier
      detection and prenatal diagnosis.

PMID- 7579330
TI  - Role of light chain variable region in myeloma with light chain deposition
      disease: evidence from an experimental model.
AB  - Light chain deposition disease (LCDD) results from a propensity of some human
      monoclonal L chains to form tissue deposits. We designed an experimental model
      for in vivo expression of human kappa L chain sequences in mice and compared a
      somatically mutated LCDD chain with a closely related control kappa chain, both
      encoded by the unique V kappa IV gene. Mice secreting the LCDD chain but not
      those producing the control chain showed deposits with a distribution similar to
      that observed in patients. These data show that discrete changes in V region
      sequences can play a major role in tissue deposition of human L chains.

PMID- 7579331
TI  - Polyclonal primitive hematopoietic progenitors can be detected in mobilized
      peripheral blood from patients with high-risk myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal
      hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow
      transplantation is the only potentially curative treatment, but remains limited
      to a small subgroup of younger patients with HLA-compatible donors. As autologous
      stem cell transplantation is currently being explored as an alternative treatment
      strategy for MDS, more information needs to be acquired regarding the clonal
      nature of the progenitor cells in these autografts. Therefore, we have analyzed
      the clonal patterns of highly purified hematopoietic progenitors and their mature
      daughter cells in mobilized peripheral blood collections produced from five
      female patients with high-risk MDS in complete hematologic remission. X
      chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 +
      33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with
      the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal
      remission was shown in all stem cell subpopulations and their mature daughter
      cells whereas one patient was found to remain skewed in all fractions, except T
      lymphocytes. This study provides strong evidence that polyclonal immature
      hematopoietic progenitors can be mobilized and harvested in patients high-risk
      MDS after treatment with high-dose chemotherapy.

PMID- 7579332
TI  - Murine thrombopoietin mRNA levels are modulated by platelet count.
AB  - The activity of the c-Mpl ligand hematopoietic progenitors meets criteria
      expected for thrombopoietin (TPO). Bio-assays have shown that blood TPO levels
      are inversely related to platelet mass. We sought to identify the molecular basis
      for this regulation. To determine if TPO mRNA levels respond to platelet demand,
      RNA from selected organs of mice with high, normal or low platelet counts was
      subjected to semiquantitative reverse transcriptase-polymerase chain reaction.
      Although no differences in TPO mRNA levels between control and treated mice could
      be detected in liver or kidney, TPO-specific bands were more intense after 25 to
      30 polymerase chain reaction cycles in marrow-derived mRNA from thrombocytopenic
      mice. The TPO-specific bands were less intense in thrombocytotic mouse marrow and
      spleen than control mouse marrow and spleen after 30 cycles. These data support
      the hypothesis that TPO levels are regulated, at least in part, by modulating
      mRNA levels in response to platelet demand.

PMID- 7579334
TI  - Antiphospholipid antibodies and venous thromboembolism.
AB  - The clinical relevance of antiphospholipid antibodies (APLA) in patients without
      systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown.
      Limited evidence suggests that there is an association between the presence of
      APLA and both initial and recurrent episodes of VTE and that patients with APLA
      and VTE are resistant to warfarin therapy. Unselected patients with a first
      episode of clinically suspected deep vein thrombosis or pulmonary embolism were
      evaluated with objective tests for VTE and with laboratory tests for APLA; the
      latter included tests for the lupus anticoagulant (LA) and anticardiolipin
      antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and
      observed during and after discontinuation of anticoagulants for symptomatic
      recurrence of VTE. There was a strong association between LA and VTE (odds ratio,
      9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to
      25%) patients with VTE had LA. There was no association between the presence of
      ACLA and VTE (odds ratio, 0.7; 95%CI, 0.3 to 1.7) because of the high frequency
      of positive ACLA assays in patients without VTE. None of the 16 patients with VTE
      and APLA developed recurrent VTE while receiving warfarin therapy. There was no
      difference in rates of recurrent VTE in patients with or without APLA after
      anticoagulant therapy was discontinued. The strong association between LA and VTE
      suggests that testing for LA in patients with VTE is useful. The measurement of
      ACLA in patients with VTE has no clinical usefulness because the results are
      abnormal in a high proportion of patients without VTE. Although the presence of
      APLA in patients with VTE was not associated with resistance to a conventional
      intensity of warfarin or an increased risk of recurrent VTE after discontinuation
      of warfarin, a larger study should address these issues in a subgroup of patients
      with VTE and LA.

PMID- 7579333
TI  - Surgery and anesthesia in sickle cell disease. Cooperative Study of Sickle Cell
      Diseases.
AB  - From 1978 to 1988, The Cooperative Study of Sickle Cell Disease observed 3,765
      patients with a mean follow-up of 5.3 +/- 2.0 years. One thousand seventy-nine
      surgical procedures were conducted on 717 patients (77% sickle cell anemia [SS],
      14% sickle hemoglobin C disease [SC], 5.7% S beta zero thalassemia, 3% S beta
      zero + thalassemia). Sixty-nine percent had a single procedure, 21% had two
      procedures, and the remaining 11% had more than two procedures during the study
      follow-up. The most frequent procedure was abdominal surgery for cholecystectomy
      or splenectomy (24% of all surgical procedures, N = 258). Of these, 93% received
      blood transfusion, and there was no association between preoperative hemoglobin A
      level and complication rates (except reduction in pain crisis). Overall mortality
      within 30 days of a surgical procedure was 1.1% (12 deaths after 1,079 surgical
      procedures). Three deaths were considered to be related to the surgical procedure
      and/or anesthesia (0.3%). No deaths were reported in patients younger than 14
      years of age. Sickle cell diseases (SCD)-related complications after surgery were
      more frequent in SS patients who received regional compared with general
      anesthesia (adjusted for risk level of the surgical procedure, patient age, and
      preoperative transfusion status, P = .058). Non-SCD-related postoperative
      complications were higher in both SS and SC patients who received regional
      compared with those who received general anesthesia (P =.095). Perioperative
      transfusion was associated with a lower rate of SCD-related postoperative
      complications for SS patients undergoing low-risk procedures (P = .006, adjusted
      for age and type of anesthesia), with crude rated of 12.9% without transfusion
      compared with 4.8% with transfusion. In SC patients, preoperative transfusion was
      beneficial for all surgical risk levels (P = .009). Thus, surgical procedures can
      be performed safely in patients with SCD.

PMID- 7579335
TI  - Synergistic effect of granulocyte colony-stimulating factor and drugs elevating
      extracellular adenosine on neutrophil production in mice.
AB  - Experimental evidence suggests that the activation of purinoceptors by
      extracellular adenosine can modulate proliferation and/or differentiation of
      hematopoietic cells. The present study was undertaken to investigate the
      potential interactions of this system of intercellular signaling with the effects
      of granulocyte colony-stimulating factor (G-CSF) on granulopoiesis in vivo.
      Elevation of extracellular adenosine in normal mice was induced by the joined
      administration of dipyridamole, a drug inhibiting the cellular uptake of
      adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects
      of dipyridamole, AMP, and G-CSF, administered either alone or in combinations,
      were evaluated. The agents were injected to mice in a 4-day regimen, and the
      hematologic endpoints were determined 24 hours after the completion of the
      treatment. It was shown that the effects of G-CSF, ie, increases in peripheral
      blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC), and
      morphologically determined granulocytic cells in femoral marrow and a decrease in
      the marrow erythroid cells, can be enhanced by the combination of dipyridamole
      plus AMP administered 30 minutes before G-CSF. Furthermore, it was ascertained
      that the stimulatory action of dipyridamole plus AMP was expressed particularly
      at lower doses of G-CSF (1.5, 3, and 4.5 micrograms/d). At higher doses of G-CSF
      (6 and 9 micrograms/d), the interactions were no more evident. When combining
      dipyridamole, AMP, and 3 micrograms of G-CSF, peripheral neutrophils increased
      approximately 3.9- to 4.5-fold compared with an approximate 2.2-fold increase
      induced by G-CSF alone. The results indicate the possible therapeutic potential
      of combination therapy with G-CSF and drugs increasing extracellular adenosine.

PMID- 7579336
TI  - Distinct regions of the granulocyte colony-stimulating factor receptor are
      required for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and
      p42, p44MAPK.
AB  - The protein tyrosine kinases JAK1 and JAK2 are phosphorylated tyrosine after the
      interaction of granulocyte colony-stimulating factor (G-CSF) with its
      transmembrane receptor. So too is Stat3, a member of the STAT family of
      transcriptional activators thought to be activated by the JAK kinases. Truncated
      G-CSF receptor (G-CSF-R) mutants were used to determine the different regions of
      the cytoplasmic domain necessary for tyrosine phosphorylation of the signaling
      molecules JAK2, Stat3, and p42, p44MAPK. We have shown that G-CSF-induced
      tyrosine phosphorylation and kinase activation of JAK2 requires the membrane
      proximal 57 amino acids of the cytoplasmic domain. In contrast, maximal Stat3
      tyrosine phosphorylation required amino acids 96 to 183 of the G-CSF-R
      cytoplasmic domain, Stat3 DNA binding could occur with a receptor truncated 96
      amino acids from the transmembrane domain and containing a single tyrosine
      residue, but was reduced in comparison with the full-length receptor. Together
      with the tyrosine phosphorylation of Stat3, this finding suggests that additional
      Stat3 does not appear to be required for proliferation. MAP kinase tyrosine
      phosphorylation correlated with both the proliferative response and JAK2
      activation.

PMID- 7579337
TI  - Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6
      on the survival of cultured human mast cells.
AB  - Although stem cell factor (SCF) has been identified as a critical cytokine for
      the development of human mast cells from their progenitors, the effects of other
      cytokines on human mast cells are less well understood. We examined the effects
      of several cytokines on the survival of human mast cells of 100% purity generated
      in suspension cultures of umbilical cord blood mononuclear cells in the presence
      of 100 ng/mL recombinant human (rh) SCF and interleukin-6 (IL-6). Mast cells
      suspended in conventional serum-containing medium died over a period of 2 to 6
      days after the withdrawal of SCF and IL-6. The cells became pyknotic and
      underwent DNA fragmentation characteristic of apoptosis. The addition of SCF, IL
      3, IL-4, IL-5, or IL-6 to the cultures in both serum-containing and serum-free
      medium prolonged their survival in a dose-dependent manner. Some other cytokines,
      such as IL-2, IL-9, IL-10, IL-11, tumor necrosis factor-alpha, transforming
      growth factor-beta 1, and nerve growth factor, had no survival-promoting effect
      at 100 ng/mL. Preincubation of mast cells with SCF, IL-4, IL-5, or IL-6 for 24
      hours during sensitization with IgE enhanced IgE/anti-IgE antibody-induced
      histamine release from mast cells, whereas IL-3 showed a negligible effect.
      Polymerase chain reaction amplification of alpha-chains of IL-3 receptor (R), IL
      4 R, IL-5 R, and IL-6 R yielded products of the correct size predicted from the
      sequence of each receptor. The binding assay using 125I-labeled IL-3 indicated
      that these mast cells bear receptors for IL-3. These findings suggest that IL-3,
      Il-4, IL-5, and IL-6, which are mainly produced by T-helper 2 lymphocytes, might
      regulate the functions of human mast cells in vivo via specific receptors in
      allergic reactions.

PMID- 7579338
TI  - Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium
      butyrate induce the CD11c integrin gene promoter activity during myeloid cell
      differentiation.
AB  - To analyze the activity of the CD11c promoter during myeloid differentiation
      without the limitations of transient expression systems, we have stably
      transfected the myeloid U937 cell line with the pCD11C361-Luc plasmid, in which
      the expression of the firefly luciferase cDNA is driven by the CD11c promoter
      region -361/+43, previously shown to confer myeloid specificity to reporter
      genes. The stable transfectants (U937-C361) retained the ability to differentiate
      in response to phorbol-ester (PMA), sodium butyrate (SB), granulocyte-macrophage
      colony-stimulating factor (GM-CSF), and other differentiating agents. U937-C361
      differentiation correlated with increased cellular luciferase levels, showing the
      inducibility of the CD11c promoter during myeloid differentiation and
      establishing the U937-C361 cells as a suitable system for studying the myeloid
      differentiation-inducing capacity of cytokines, growth, factors, and other
      biological response modifiers. Unexpectedly, the inducibility of the CD11c gene
      promoter showed distinct kinetics and magnitude on the PMA-, SB-, GM-CSF
      triggered differentiation. Moreover, SB synergized with either PMA or GM-CSF in
      enhancing both the CD11c promoter activity and the cell surface expression of
      p150,95 on differentiating U937 cells. Furthermore, we showed the existence of a
      c-Myb-binding site at -85, the importance of the -99/-61 region in the CD11c
      promoter inducibility during PMA- or SB-triggered differentiation, and the
      dependency of the GM-CSF and PMA responsiveness of the CD11c promoter on an
      intact AP-1-binding site located at -60. These results, together with the lack of
      functional effect of mutations disrupting the Sp1-and Myb-binding sites within
      the proximal region of the CD11c promoter, indicate that the myeloid
      differentiation pathways indicated by SB and phorbol esters (or GM-CSF) activate
      a distinct set of transcription factors and show that the myeloid differentiation
      inducibility of the CD11c gene maps to the -99/-53 proximal region of the
      promoter.

PMID- 7579339
TI  - Unilineage megakaryocytic proliferation and differentiation of purified
      hematopoietic progenitors in serum-free liquid culture.
AB  - Cellular and molecular analysis of megakaryocytopoiesis has been hampered thus
      far by the lack of pure and abundant megakaryocyte (MK) cell populations. In this
      study, hematopoietic progenitor cells (HPCs), stringently purified from
      peripheral blood, were induced to megakaryocytic differentiation/maturation in
      serum-free liquid suspension culture treated with a growth factor cocktail
      (interleukin-3 [IL-3], c-kit ligand, and IL-6) and/or recombinant mpl ligand
      (mpIL). In particular, (1) the growth factor cocktail induced the growth of a 40%
      MK population, ie, 4 x 10(4) cells at day 0 generated 2 x 10(5) MK at terminal
      maturation; (2) further addition of mpIL increased the MK purity level to 80%
      with a final yield of 4 x 10(5) MKs; (3) treatment with mpIL alone resulted in a
      97% to 99% MK population, with a mild increase of cell number (to 1.5 x 10(5)
      cells). In mpIL-supplemented culture, morphological evaluation indicated the
      presence of putative mononuclear MK precursors and then of mature polynucleated
      platelet-forming MKs, peaking at days 5 and 12, respectively. Membrane phenotype
      analysis showed a gradual decrease of CD34+ HPCs, coupled with an inverse
      increase of MK-specific antigens (eg, CD61/62/42b) starting before mature MK
      detection by morphology analysis. In situ hybridization showed the expression of
      MK-specific von Willebrand gene in both MK precursors and mature MKs.
      Furthermore, MKs synthesize and secrete low but significant amounts of both IL-6
      and granulocyte-macrophage colony-stimulating factor. Comparative culture studies
      were performed on purified bone marrow CD34+/38hi or CD34+/38lo cells stimulated
      by mpIL alone. Both populations generated a highly enriched MK progeny (62% and
      93% MKs at day 12 of culture, respectively) but showed either little or no
      proliferation. In conclusion, the purified peripheral blood HPC differentiation
      culture system allows for growth of a relatively large number of highly purified
      or "pure" megakaryocytic precursors and then mature MKs, thus providing an in
      vitro experimental tool to dissect the cellular and molecular basis of
      megakaryocytopoiesis.

PMID- 7579340
TI  - Changing the differentiation program of hematopoietic cells: retinoic acid
      induced shift of eosinophil-committed cells to neutrophils.
AB  - The mechanisms by which hematopoietic progenitor cells become lineage-committed
      remain poorly understood. A cloned subline of the AML14 cell line (AML14.3D10)
      that spontaneously differentiates to eosinophilic myelocytes in the absence of
      cytokine stimulation was obtained by limiting dilution. This subline exhibits
      augmented expression of interleukin-5 (IL-5) receptor alpha subunit mRNA and
      synthesizes all major eosinophil granule proteins. Exposure of this cell line to
      all-trans retinoic acid (ATRA) causes loss of eosinophilic granules and fast
      green staining within 48 hours, without cell death. In addition, mRNA for the IL
      5 receptor alpha subunit becomes undetectable by 48 hours and the cells lose
      responsiveness to IL-5. Major basic protein, measured as a marker of eosinophilic
      granule content, decreases from more than 16 pg/cell to undetectable levels by 5
      days after ATRA. Concomitant with the loss of major basic protein and fast green
      staining, surface expression of CD16 becomes detectable and is maximum by 10 days
      after ATRA. mRNA for the granulocyte colony-stimulating factor (G-CSF) receptor
      becomes detectable by day 5, and the cells become responsive to G-CSF. At this
      time, the cells appear morphologically as mature neutrophils and can reduce
      nitroblue tetrazolium. With continued culture, the neutrophilic cells die and the
      culture becomes repopulated with eosinophilic myelocytes. These findings show
      that it is possible to change the differentiation program of hematopoietic cells
      even after they show evidence of advanced lineage commitment. The AML14.3D10
      subclone of AML14 will be a valuable model for study of the transcriptional
      regulation of the eosinophil and neutrophil differentiation programs and lineage
      specific gene expression.

PMID- 7579341
TI  - A functional comparison of CD34 + CD38- cells in cord blood and bone marrow.
AB  - We present cell cycling and functional evidence that the CD34+CD38-
      immunophenotype can be used to define a rare and primitive subpopulation of
      progenitor cells in umbilical cord blood. CD34+CD38- cells comprise 0.05% +/-
      0.08% of the mononuclear cells present in cord blood. Cell cycle analysis with
      the fluorescent DNA stain 7-aminoactinomycin D showed that the percentage of
      CD34+ cells in cycle directly correlated with increasing CD38 expression.
      CD34+CD38- cord blood cells were enriched for long-term culture-initiating cells
      (LTCIC; cells able to generate colony-forming unit-cells [CFU-C] after 35 to 60
      days of coculture with bone marrow stroma) relative to CD34+CD38- cells. In an
      extended LTCIC assay, CD34+CD38- cells were able to generate CFU-C between days
      60 and 100, clearly distinguishing them from CD34+CD38+ cells that did not
      generate CFU-C beyond day 40. When plated as single cells, onset of clonal
      proliferation was markedly delayed in a subpopulation of CD34+CD38- cells; clones
      (defined as > 100 cells) appeared after 60 days of culture in 2.9% of CD34+CD38-
      cells. In contrast, 100% of CD34+CD38+ cells formed clones by day 21. Although
      the CD34+CD38- immunophenotype defines highly primitive populations in both bone
      marrow and cord blood, important functional differences exist between the two
      sources. CD34+CD38- cord blood cells have a higher cloning efficiency,
      proliferate more rapidly in response to cytokine stimulation, and generate
      approximately sevenfold more progeny than do their counterparts in bone marrow.

PMID- 7579342
TI  - Retroviral-mediated gene transfer in human bone marrow cells growth in continuous
      perfusion culture vessels.
AB  - Hematopoietic stem cell gene therapy holds the promise of being able to treat a
      variety of inherited and acquired diseases of the hematopoietic stem cell.
      However, to date, genetic modification of the human hematopoietic stem cell has
      been relatively inefficient. Here, we report the results of using a bioreactor
      system to expand hematopoietic cells after a brief retrovirus infection using a
      high titer, replication defective virus encoding for murine CD18. The retrovirus
      transduced culture continued to produce genetically modified hematopoietic
      progenitors for up to 6 weeks, the duration of the culture period. Up to one
      third of the long-term culture initiating cell (LTC-IC) are genetically modified
      by the culture conditions. Murine CD18 can be expressed on the cell surface of up
      to 20% of the mature cells generated by the culture system, suggesting that
      clinically significant levels of gene transfer may be occurring. These results
      demonstrate the feasibility of using continuous perfusion bioreactors as a method
      of efficiently modifying human hematopoietic stem cells.

PMID- 7579343
TI  - In vitro biosynthesis of leukemia inhibitory factor/human interleukin for DA
      cells by human endothelial cells: differential regulation by interleukin-1 alpha
      and glucocorticoids.
AB  - Endothelial cell (EC) may represent a major source of cytokines in the bone
      marrow. In this study we have examined the production and the regulation of the
      production of leukemia inhibitory factor/human interleukin for DA cells
      (LIF/HILDA) by EC. Human umbilical vein endothelial cells (HUVEC) were chosen as
      a working model as they are a well known source of cytokines. These cells secrete
      LIF/HILDA (90 pg/mL/10(6) cells/48 h) in basal conditions. This secretion is
      profoundly altered by interleukin-1 alpha (IL-1 alpha). Secretion of LIF/HILDA is
      increased threefold on stimulation with IL-1 alpha at a concentration of 100
      IU/mL. The secreted protein is bioactive as demonstrated by its proliferative
      effects on DA1a cells. Modulation of the production of LIF/HILDA by
      glucocorticoids (GC) was also examined. In striking contrast to what was observed
      for IL-1 alpha, the synthetic GC dexamethasone (DXM) at a concentration of 10(-6)
      mol/L consistently inhibited the basal secretion of LIF/HILDA by an average of
      threefold and suppressed the IL-1 alpha-induced increase of the secretion of this
      cytokine by HUVEC. In an effort to extend results obtained with HUVEC to the bone
      marrow endothelium, we have also examined the production of LIF/HILDA by human
      bone marrow endothelial cells (HBMEC). Our study shows that HBMEC are
      quantitatively a very important source of this cytokine (above 7.25 ng/mL/10(6)
      cells/48 h) suggesting that they are a major source of LIF/HILDA in the bone
      marrow. Again, IL-1 alpha proved to be a very potent stimulus for the secretion
      of LIF/HILDA and synthetic GC such as DXM when used at a concentration of 10(-6)
      mol/L inhibited by an average of threefold the basal secretion of LIF/HILDA and
      had suppressive effect on the IL-1 alpha-induced increase of this secretion. The
      downregulation of LIF/HILDA production in the bone marrow by GC may be important
      to understand the effects of GC on hematopoiesis.

PMID- 7579344
TI  - The value of flow cytometric analysis of platelet glycoprotein expression of
      CD34+ cells measured under conditions that prevent P-selectin-mediated binding of
      platelets.
AB  - In the present study, we show by adhesion assays and ultrastructural studies that
      platelets can bind to CD34+ cells from human blood and bone marrow and that this
      interaction interferes with the accurate detection of endogenously expressed
      platelet glycoproteins (GPs). The interaction between these cells was found to be
      reversible, dependent on divalent cations, and mediated by P-selectin. Enzymatic
      characterization showed the involvement of sialic acid residues, protein(s). The
      demonstration of mRNA for the P-selectin glycoprotein ligand 1 (PSGL-1) in the
      CD34+ cells by polymerase chain reaction (PCR) analysis suggests that this
      molecule is present in these cells. Under conditions that prevent platelet
      adhesion, a small but distinct subpopulation of CD34+ cells diffusely expressed
      the platelet GPIIb/IIIa complex. These cells were visualized by immunochemical
      studies. Furthermore, synthesis of mRNA for GPIIb and GPIIIa by CD34+ cells was
      shown using PCR analysis. The semiquantitative PCR results show relatively higher
      amounts of GPIIb mRNA than of PF4 mRNA in CD34+CD41+ cells in comparison with
      this ratio in platelets. This finding is a strong indication that the PCR results
      are not caused by contaminating adhering platelets. MoAbs against GPIa GPIb
      alpha, GPV, P-selectin, and the alpha-chain of the vitronectin receptor did not
      react with CD34+ cells. The number of CD34+ cells expressing GPIIb/IIIa present
      in peripheral blood stem cell (PBSC) transplants was determined and was
      correlated with platelet recovery after intensive chemotherapy in 27 patients.
      The number of CD34+CD41+ cells correlated significantly better with the time of
      platelet recovery after PBSC transplantation (r = .83, P = .04) than did the
      total number of CD34+ cells (r = .55). Statistical analysis produced a threshold
      value for rapid platelet recovery of 0.34 x 10(6) CD34+CD41+ cells/kg. This study
      suggests that if performed in the presence of EDTA the flow cytometric
      measurement of GPIIb/IIIa on CD34+ cells provides the most accurate indication of
      the platelet reconstitutive capacity of the PBSC transplant.

PMID- 7579345
TI  - Cyclin D3 is essential for megakaryocytopoiesis.
AB  - A normal cell cycle in most eukaryotic cells consists of a tightly regulated
      sequence of phases including DNA synthesis (S) followed by a gap (G2), mitosis
      (M), and a gap (G1). In the megakaryocytic lineage, the cells undergo
      endomitosis, which involves DNA synthesis in the absence of mitosis, thus giving
      rise to polyploid cells. We aimed at defining whether the megakaryocytic cell
      cycle consists of a continuous S phase or of G1/S phases and at determining which
      cyclins are involved in this process. Studies were performed in primary cultures
      of mouse bone marrow cells. DNA synthesis in megakaryocytes was followed by
      determining incorporation of a DNA precursor, bromodeoxyuridine (BrdU), into the
      cells by in situ staining for BrdU. These experiments showed that no more than
      15% of the recognizable megakaryocytes in normal bone marrow are in the process
      of endomitosis, including S phases interrupted by short gaps. Using
      immunohistochemistry, we showed that mature megakaryocytes express the G1 phase
      cyclin and cyclin D3, but not the mitotic cyclin, cyclin B1. Under culture
      conditions that selectively promote megakaryocytopoiesis, antisense
      oligonucleotides designed to suppress cyclin D3 expression, but not sense
      oligonucleotides or antisense oligonucleotides to cyclin B1, dramatically
      suppress endomitosis and abrogate megakaryocyte development. Our results indicate
      that endoreduplication in megakaryocytes is associated with low levels of or the
      absence of cyclin B1, whereas progression through this process depends on the G1
      phase for which cyclin D3 is crucial.

PMID- 7579346
TI  - Extracellular epitopes of platelet glycoprotein Ib alpha reactive with serum
      antibodies from patients with chronic idiopathic thrombocytopenic purpura.
AB  - Glycoproteins (GPs) IIb/IIIa and Ib/IX are principal targets of autoantibodies
      (autoAbs) in idiopathic thrombocytopenic purpura (ITP). Platelet-associated Abs
      against GPIIb/IIIa primarily recognize discontinuous or nonlinear epitopes
      (Fujisawa et al, Blood 81:1284, 1993). This study focused on whether Abs against
      the extracellular domain of GPIb/IX might react with short linear amino acid (aa)
      sequences of GPIb alpha. Complementary DNAs (cDNAs) coding for two overlapping
      fragments of GPIb alpha were amplified, cloned into pFLAG.2 plasmids, and
      expressed in Escherichia coli DH5 alpha competent cells as FLAG fusion proteins,
      which were purified by anti-FLAG immunoaffinity chromatography. Of 16 selected
      ITP sera containing anti-GPIb/IX, 6 reacted in microtiter radioimmunoassays
      (RIAs) with recombinant protein fragment 2 (aas 240 to 485); 1 also with fragment
      1 (aas 1 to 247). When synthetic peptides corresponding to 4 segments of fragment
      2 with high antigenic indices (P1 to P4) were used as targets in RIAs, all 6 sera
      reacted with P2 (aas 326 to 346); 1 also reacted with P4 (aas 389 to 412). P2 was
      shown to be present on the surface of intact platelets by adsorption studies, and
      anti-P2 was detected in direct eluates of platelets from ITP patients.
      Glycocalicin in solution effectively competed with immobilized P2 for anti-P2; P2
      in solution was a less effective competitor. Epitope scanning with a panel of
      synthetic 15-mer peptides localized the P2 epitope to the sequence, TKEQTTFPP.
      Epitope definition may offer insight into the pathophysiology of and more
      specific treatments for ITP.

PMID- 7579347
TI  - The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused
      by mutations of the same gene.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder
      characterized by thrombocytopenia, small platelets, eczema, recurrent infections,
      and immunodeficiency. Besides the classic WAS phenotype, there is a group of
      patients with congenital X-linked thrombocytopenia (XLT) who have small platelets
      but only transient eczema, if any, and minimal immune deficiency. Because the
      gene responsible for WAS has been sequenced, it was possible to correlate the WAS
      phenotypes with WAS gene mutations. Using a fingerprinting screening technique,
      we determined the approximate location of the mutation in 13 unrelated WAS
      patients with mild to severe clinical symptoms. Direct sequence analysis of cDNA
      and genomic DNA obtained from patient-derived cell lines showed 12 unique
      mutations distributed throughout the WAS gene, including insertions, deletions,
      and point mutations resulting in amino acid substitutions, termination, exon
      skipping, or splicing defects. Of 4 unrelated patients with the XLT phenotype, 3
      had missense mutations affecting exon 2 and 1 had a splice-site mutation
      affecting exon 9. Patients with classic WAS had more complex mutations, resulting
      in termination codons, frameshift, and early termination. These findings provide
      direct evidence that XLT and WAS are caused by mutations of the same gene and
      suggest that severe clinical phenotypes are associated with complex mutations.

PMID- 7579348
TI  - The genetic defect in two well-studied cases of Bernard-Soulier syndrome: a point
      mutation in the fifth leucine-rich repeat of platelet glycoprotein Ib alpha.
AB  - Bernard-Soulier syndrome (B-Ss) is a rare congenital bleeding disorder caused by
      abnormal giant platelets, thrombocytopenia, and defective glycoprotein (GP) Ib-V
      IX, the adhesion receptor for von Willebrand factor (vWF). This report describes
      the molecular defect in two related individuals with well-established B-Ss whose
      platelets exhibit decreased GPIb-IX and normal GPV on their surfaces. The GPIb-V
      IX genes of the two patients were analyzed by Southern blotting, hetero-duplex
      analysis, and polymerase chain reaction (PCR) amplification/sequencing. A point
      mutation was found in codon 129 of the GPIb alpha gene that results in the
      substitution of proline for leucine in the first position of the fifth leucine
      rich glycoprotein repeat of the mature gene product. The mutation (CTC: leucine,
      wild-type to CCC: proline, mutant) eliminates a Sac I restriction site,
      facilitating analysis of the mutation in the propositi (both homozygotes),
      unaffected family members (8 heterozygotes and 8 wild-type), and 58 normal
      controls (116 wild-type alleles). The status of the genomes was confirmed by the
      sequencing of platelet cDNA. The mutation does not affect transcription of the Ib
      IX genes, as estimated by PCR and Northern blot analysis, but it does inhibit
      surface expression of the receptor as assessed by transient transfection of
      mutant and wild-type GPIb alpha genes into mouse Ib beta-IX L cells. Many of the
      cells (43%) transfected with the normal gene express surface GPIb alpha, whereas
      untransfected cells and those transfected with the mutant gene lack surface GPIb
      alpha entirely. Patient platelets were tested both for vWF binding in the
      presence of ristocetin and for surface GPIb-IX expression. In these instances,
      despite their inability to agglutinate with ristocetin and vWF, patient platelets
      exhibit about 40% of normal vWF binding and 40% of normal Ib-IX surface antigens.
      The results suggest that the described mutation (GPIb alpha: Leu129 -> Pro)
      affects the conformation of the GPIb-V-IX receptor, alters its availability on
      platelet surfaces, and causes the observed Bernard-Soulier phenotype.

PMID- 7579349
TI  - Role of collagen-adherent platelets in mediating fibrin formation in flowing
      whole blood.
AB  - Activated platelets provide assembly sites for coagulation enzyme complexes and
      in this way can mediate coagulation during hemostasis and thrombosis. In this
      study, we examined the procoagulant activity of platelets adhering directly to
      fibrillar collagen, a main thrombogenic constituent of subendothelium. For this
      purpose, we used a human ex-vivo thrombosis model in which collagen-coated
      coverslips were exposed to flowing nonanticoagulated blood (shear rate, 65/s) for
      5.5 minutes, which led to the deposition of adherent platelets, platelet thrombi,
      and fibrin. To examine the procoagulant activity of adherent platelets only, a
      selective antagonist of the platelet GPIIb-IIIa complex, Ro 44-9883, was infused
      via a mixing device, resulting in a complete abrogation of platelet thrombus
      formation but leaving the collagen-adherent platelet layer intact. This platelet
      layer generated increased postchamber fibrinopeptide A (FPA) levels (203 +/- 33
      ng/mL) as compared with control experiments without infusion of inhibitor (95 +/-
      13 ng/mL). Concomitantly, fibrin deposition measured by morphometric analysis of
      cross-sections was also increased, as was the platelet adhesion to collagen. An
      immunochemical staining of fibrin fibers further showed that the adherent
      platelets formed the nuclei for fibrin fiber formation. This increase in fibrin
      deposition was mediated by the intrinsic factor X (F.X) activation complex on
      adherent single platelets, because almost complete inhibition of FPA generation
      (9 ng/mL) and fibrin deposition (0.4% +/- 0.2% coverage) was achieved upon
      coinfusion of the GP IIb-IIIa antagonist and active site-inhibited F.IXa. The
      large platelet thrombi that were deposited in control experiments contained no
      significant amounts of immunodetectable fibrin except at the thrombus base, where
      adherent platelets anchored the thrombi to the collagen surface. These results
      suggest that the collagen-adherent platelets are important promoters of
      coagulation during the initial phase of thrombogenesis by providing assembly
      sites for the F.X activation complex.

PMID- 7579351
TI  - The major histocompatibility complex region marked by HSP70-1 and HSP70-2
      variants is associated with clozapine-induced agranulocytosis in two different
      ethnic groups.
AB  - Genes of the major histocompatibility complex (MHC) have been associated with
      susceptibility to drug-induced adverse reactions. We previously found that
      clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402,
      DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with
      the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish
      patients. In the present study, we tested the hypothesis that the variants of the
      heat-shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC
      region and known to be involved in apoptosis and regulation of cell proliferation
      could play an important role in molecular mechanisms of CA. First, we analyzed
      HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and
      normal individuals and confirmed that the HSP70-2 9-kb variant was associated
      invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601,
      DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the
      haplotypes found increased in Jewish and non-Jewish patients with CA,
      respectively. The 9.0-kb variant was also found to be associated with HLA-B44,
      DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12
      Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb
      variants were associated with the MHC haplotypes found by us to be markers of
      susceptibility to CA. The clozapine-treated control group had an excess number of
      HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA
      associated with those variants. This finding supports our hypothesis that a
      dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not
      necessarily HLA, is associated with CA in two different ethnic groups.

PMID- 7579350
TI  - The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2 gene
      expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells.
AB  - The regulatory Tat protein of human immunodeficiency virus type-1 (HIV-1) exerts
      a pleyotropic activity on the survival and proliferation of different cell types
      in culture. In this report, we investigated the effect of either endogenous or
      exogenous Tat on Bcl-2 proto-oncogene expression and cell survival in Jurkat T
      cell lines and primary peripheral blood mononuclear cells. Stable and transient
      transfections of Jurkat cells with the cDNA of tat and a plasmid containing Bcl-2
      promoter in front of CAT (Bcl-2 Pr/CAT) stimulated CAT activity and showed an
      increase of Bcl-2 mRNA and protein expression. This effect was specifically
      related to tat, because Jurkat cells transfected with the cDNA of tat in
      antisense orientation, tat carrying a mutation in the amino acid cys22-gly22, or
      the control vector alone (pRPneo-SL3) did not show any significant difference in
      Bcl-2 promoter activity with respect to parental Jurkat cells. We also observed a
      specific correlation between tat-induced Bcl-2 gene expression and inhibition of
      apoptosis induced by serum withdrawal. Our results suggest that the structural
      integrity of the activation domain of Tat was required for the promotion of the
      Bcl-2 promoter and Jurkat cell survival, because a single mutation in the
      aminoacid cys22 was sufficient to completely block the upregulation of Bcl-2 and
      inhibition of apoptosis. Moreover, picomolar concentrations of native or
      recombinant Tat were able to upregulate Bcl-2 expression both in Jurkat and
      primary peripheral blood mononuclear cells, suggesting that extracellular Tat,
      actively released by infected cells, may also play a significant role in
      suppressing apoptosis. An aberrant cell survival of lymphoid cells consequent to
      the upregulation of Bcl-2 may represent an additional pathogenetic mechanism that
      could help explain both the dysregulated immune response and the frequent
      occurrence of hyperplastic/neoplastic disorders in HIV-1-seropositive
      individuals.

PMID- 7579352
TI  - Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are
      elevated in human sepsis.
AB  - Because of their effects on monocytes, monocyte chemotactic proteins-1 and -2
      (MCP-1 and MCP-2) may participate in the pathophysiology of sepsis. We measured
      circulating MCP-1 and MCP-2 levels in 42 septic patients having positive local or
      blood cultures. MCP-1 and MCP-2 levels were elevated in 24 (57%) and 25 (59%) of
      42 septic patients, respectively, compared with healthy volunteers. Both patients
      with gram-positive and gram-negative infections had elevated MCP-1 plasma levels
      (P = .0001) and P < .0001), respectively; Mann-Whitney-U test), whereas patients
      with gram-positive infection, but not those with gram-negative infection, had
      increased MCP-2 plasma levels (P= .0182). No relative differences in MCP-1 and
      MCP-2 plasma levels were observed between several subgroups of patients (sepsis v
      septic shock; survivors v nonsurvivors), although levels of MCP-1 were the
      highest in patients with the more severe forms of sepsis, ie, those with shock or
      a lethal outcome. Serial observations showed that MCP-1 and MCP-2 plasma levels
      remained elevated for at least 48 hours. MCP-1 correlated weakly with interleukin
      8 and MCP-2, the correlations for which were most pronounced in patients with
      septic shock. MCP-2 correlated with interleukin-8, and surprisingly, with the
      complement activation product C3a; these correlations further improved when
      analyzing patients with septic shock or when applying gram-positive infections.
      Thus, our results not only show increased MCP-1 and MCP-2 levels in patients with
      sepsis, but also suggest that the synthesis and release of MCP-1 and MCP-2 in
      sepsis are differently regulated in part.

PMID- 7579353
TI  - Fas receptor (CD95)-mediated apoptosis is induced in leukemic cells entering G1B
      compartment of the cell cycle.
AB  - Apoptotic cell death induced by cross-linking Fas receptor (FasR/CD95) has been
      investigated in human acute myelogenous leukemia (AML) cells. FasR-mediated
      growth inhibition and DNA fragmentation could be induced in certain cases of AML.
      Interestingly, when DNA synthesis and G1 -> S transition in the cell cycle were
      enhanced by interleukin-3 or granulocyte-macrophage colony-stimulating factor,
      Fas-insensitive blast cells acquired cellular susceptibility toward FasR-mediated
      growth inhibition. To further evaluate an association between the Fas-R-mediated
      action and a specific phase of the cell cycle, a FasR+ leukemic cell line, MML-1,
      was established from a patient with AML. The morphologic feature of dying cells
      and DNA fragmentation indicated that FasR cross-linking induced apoptotic cell
      death in MML-1 cells. Cell cycle arrest in G1A phase with the treatment of
      phorbol 12-myristate 13-acetate or thymidine rendered MML-1 cells resistant to
      FasR-mediated apoptosis without downregulation of surface FasR expression.
      However, S-phase arrest with 5-fluorouracil could neither enhance nor inhibit
      FasR-mediated apoptosis. Simultaneous DNA/RNA quantification analysis revealed
      the selective loss of cells in G1B compartment, accompanied by the increase of
      apoptotic nuclei in sub-G1 fraction. These findings suggested that FasR-mediated
      apoptotic signals could be transduced into cells in G1B compartment and G1A ->
      G1B transition might augment the induction of FasR-mediated apoptosis.

PMID- 7579354
TI  - In vitro cellular drug resistance in children with relapsed/refractory acute
      lymphoblastic leukemia.
AB  - Cellular drug resistance is thought to be an important cause of the poor
      prognosis for children with relapsed or refractory acute lymphoblastic leukemia
      (ALL), but it is unknown when, to which drugs, and to what extent resistance is
      present. We determined in vitro resistance to 13 drugs with the MTT assay.
      Compared with 141 children with initial ALL, cells from 137 children with
      relapsed ALL were significantly more resistant to glucocorticoids, L
      asparaginase, anthracyclines, and thiopurines, but not to vinca-alkaloids,
      cytarabine, ifosfamide, and epipodophyllotoxins. Relapsed ALL cells expressed the
      highest level of resistance to glucocorticoids, with a median level 357- and >24
      fold more resistant to prednisolone and dexamethasone, respectively, than initial
      ALL cells, whereas the resistance ratios for the other drugs differed from 0.8-
      to 1.9-fold, intraindividual comparisons between initial and relapsed samples
      from 16 children with ALL showed that both de novo and acquired drug resistance
      were involved. Specific in vitro drug-resistance profiles were associated with
      high-risk relapsed ALL groups. In vitro drug resistance was also related to the
      clinical response to chemotherapy in relapsed/refractory childhood ALL. We
      conclude that drug resistance may explain the poor prognosis for children with
      relapsed/refractory ALL. These day may be helpful to design alternative treatment
      regimens for relapsed childhood ALL.

PMID- 7579355
TI  - Loss of heterozygosity in the chromosomal region 12p12-13 is very common in
      childhood acute lymphoblastic leukemia and permits the precise localization of a
      tumor-suppressor gene distinct from p27KIP1.
AB  - Abnormalities of the short arm of chromosome 12 are relatively common in
      hematologic malignancies and deletions of the region. 12p12-13 are found in
      approximately 5% of the patients with acute lymphoblastic leukemia (ALL). As a
      potent inhibitor of cyclin-dependent kinases, p27KIP1 prevents the progression of
      the cell cycle and the gene encoding p27KIP1 represents a potential tumor
      suppressor gene. Its recent assignment to the chromosomal region (12p12.3)
      prompted us to study the p27KIP1 gene in a series of 61 children with ALL.
      Microsatellite polymorphic markers flanking the p27KIP1 gene were analyzed to
      detect losses of heterozygosity (LOH). Eleven patients displayed LOH for at least
      one of the markers. The deleted are encompassed the p27KIP1 gene locus in 10
      cases, but inactivation of the remaining allele by deletion, translocation, or
      mutation was never observed. In addition, in 1 patient, the p27KIP1 gene was
      situated outside of the region of LOH. Thus, p27KIP1 does not seem to be the
      target gene of 12p12-13 alterations. However, this study indicates that 12p12-13
      alterations at the molecular level, which are present in about 27% of the
      children with B-lineage ALL, are much more common than had previously been
      reported by usual chromosome analysis. Moreover, LOH mapping allowed us to better
      define the location of a putative tumor-suppressor gene implicated in these
      malignancies and should therefore help in identifying this gene.

PMID- 7579356
TI  - Molecular analysis of infant acute lymphoblastic leukemia: MLL gene rearrangement
      and reverse transcriptase-polymerase chain reaction for t(4; 11)(q21; q23).
AB  - Molecular techniques to detect MLL (11q23) and AF-4 (4q21) gene rearrangements
      are being evaluated for use in stratification of patients into prognostic groups.
      We studied 15 cases of infant acute lymphoblastic leukemia (ALL) with Southern
      blotting for MLL gene rearrangement and reverse transcriptase-polymerase chain
      reaction (RT-PCR) for t(4;11) fusion transcripts and compared the results to
      cytogenetic and clinical data. Our results indicate that classic t(4;11)(q21;q23)
      translocations are detected by RT-PCR; however, unusual 4;11 translocations still
      require additional investigation. We also extended and updated our original study
      of MLL gene rearrangement in infant ALL to 40 patients with longer follow-up and
      show that the group with germline configuration of the MLL gene continues to have
      an excellent outcome. The results of salvage therapy (bone marrow transplantation
      or chemotherapy) suggest that transplant may show advantage. Preliminary results
      of the use of RT-PCR to assess minimal disease are also reported.

PMID- 7579357
TI  - Analysis of VH gene expression in CD5+ and CD5- B-cell chronic lymphocytic
      leukemia.
AB  - In contrast to highly mutated follicular lymphomas and multiple myelomas, chronic
      lymphocytic leukemias (CLLs) frequently express VH genes in germline
      configuration. It is currently unclear whether this difference is related to the
      expression of CD5 or to the differentiation stage of the B cell when malignant
      transformation occurs. We have studied the VH sequence of 11 cases of CD5- B-CLL
      to address the question whether CD5- B-CLL are derived from naive pregerminal B
      cells (low mutation pattern) or from germinal center-derived memory B cells (high
      mutation pattern). Among the 12 detected rearrangements (2 distinct
      rearrangements in 1 case) VH1 family was found in 2, VH2 in 2, VH3 in 4, and VH4
      in 4. Nine different VH genes were detected among the 12 rearrangements,
      including 2 cases expressing V1-69 (51p1) and 1 case expressing V4-39 (VH4.18),
      previously reported to be overexpressed in CD5+ B-CLL. A higher mutation pattern,
      following a random distribution, was observed when compared with classical CD5+ B
      CLL. However, as reported in normal B cells, these results appeared to be related
      to membrane Ig phenotype (less mutations in membrane mu delta-expressing forms in
      leukemias expressing exclusively membrane mu). Overall, the differences found
      when comparing the mutational profile with classical CD5+ B-CLL were not clearcut
      and might be explained more by the membrane isotype (mu v mu delta) than by CD5
      expression.

PMID- 7579358
TI  - BCR-ABL antisense oligodeoxyribonucleotides suppress the growth of leukemic and
      normal hematopoietic cells by a sequence-specific but nonantisense mechanism.
AB  - We have examined the effect of BCR/ABL junctional antisense phosphodiester
      oligodeoxyribonucleotides (ODNs) on BV173 and other chronic myeloid leukemia
      (CML) cell lines. Various control ODNs were used to understand the mechanism of
      the observed antiproliferative effect. Not only the antisense ODNs but also
      several control ODNs inhibit the proliferation of the leukemic cell lines. All
      the ODNs that inhibit the cell proliferation share a TAT consensus sequence at
      their 3' end. A 1-base mismatch within this consensus sequence abolishes the
      antiproliferative effect. Mismatches of several bases at any other position
      within the sequence of the active ODNs do not suppress the observed effect.
      Similar experiments on normal or CML CD34+ cell fraction led to the same
      observations. We conclude that the antiproliferative effect of the phosphodiester
      BCR/ABL antisense ODNs cannot be attributed to an antisense mechanism but rather
      to a nonelucidated effect of a 3' terminal TAT sequence. This effect is not CML
      specific.

PMID- 7579359
TI  - The SH2 domain of P210BCR/ABL is not required for the transformation of
      hematopoietic factor-dependent cells.
AB  - Src-homology region 2 (SH2) domains, by binding to tyrosine-phosphorylated
      sequences, mediate specific protein-protein interactions important in diverse
      signal transduction pathways. Previous studies have shown that activated forms of
      the Abl tyrosine kinase, including P210BCR/ABL of human chronic myelogenous
      leukemia, require the SH2 domain for the transformation of fibroblasts. To
      determine whether SH2 is also required for Bcr/Abl to transform hematopoietic
      cells, we have studied two SH2 domain mutations in P210BCR/ABL: a point mutation
      in the conserved FLVRES motif (P210/R1033K), which interferes with
      phosphotyrosine-binding by SH2, and a complete deletion of SH2 (P210/delta SH2).
      Despite a negative effect on intrinsic Abl kinase activity, both P210 SH2 mutants
      were still able to transform the hematopoietic factor-dependent cell lines Ba/F3
      and FDC-P1 to growth factor independence. Unexpectedly, both mutants showed
      greater transforming activity than wild-type P210 in a quantitative
      transformation assay, probably as a consequence of increased stability of the SH2
      mutant proteins in vivo. Cells transformed by both P210 SH2 mutants were
      leukemogenic in synaptic mice and P210/r1053K mice exhibited a distinct disease
      phenotype, reminiscent of that induced by v-Abl. These results demonstrate that
      while the Abl SH2 domain is essential for BCR/ABL transformation of fibroblasts,
      it is dispensable for the transformation of hematopoietic factor-dependent cell
      lines.

PMID- 7579360
TI  - Cytogenetic evolution patterns in non-Hodgkin's lymphoma.
AB  - Secondary chromosomal aberrations were surveyed in non-Hodgkin's lymphomas (NHL)
      reported in the literature with one of the following, presently recognized,
      primary abnormalities: t(2;5), +3, t(3;14), del(6q), +X, and -Y. Of 2,175 NHLs
      with clonal karyotypic changes, 908 (42%) had one of the 13 selected primary
      chromosome rearrangements, and 670 (74%) of these lymphomas displayed additional
      abnormalities. The type and frequency of the secondary aberrations were
      ascertained and then correlated with both the type of primary abnormality and
      morphologic subtype; low-, intermediate, and high-grade according to the Working
      Formulation. The incidence of secondary aberrations differed not only among the
      primary abnormality subgroups, from 0% in del(11q) NHLs to 93% in t(3;14)
      lymphomas (P < .001) but also between B- and T-cell NHLs (78% versus 55%, P<
      .001) and among the different histologic subgroups: 66% in low-, 85% in
      intermediate-, and 71% in high-grade lymphomas (P < .001). The mean number of
      secondary changes per case also varied among the primary abnormalities, from none
      in del(11q) NHLs to 12.0 in inv(14) lymphomas (P < .001), and among the
      morphologic subtypes: 4.6 in low-, 6.7 in intermediate-, and 3.6 in high-grade
      NHL (P < .001). Recurrent secondary aberrations were found in 6 of the 13 primary
      abnormality subgroups: t(2;5), t(3;14), t(8;14), t(11;14), inv(14), and t(14;18).
      The most frequent secondary aberrations were +X, -Y, dup(1q), del(6q) varied both
      within and among the primary abnormalities; the most frequent imbalances were a
      gain of 1q23-31 and losses of 6q21, 6q23, and 6q25. Other common imbalances were
      deletions of 1p31-36, 1q31-44, 2q34-37, 7q35-36, 9p22-24, 11q23-25, 13q13-21, and
      duplication of 12q13-22. The distribution of the secondary changes was clearly
      nonrandom with the most common anomalies being -Y and +7 in t(2;5); +X, del(6q),
      and +7 in t(3;14); dup(1q) and +7 in t(8;14); -Y, del(6q), and -13 in t(11;14);
      del(6q), -17, and -18 in inv(14); and del(6q), +7, and +12 in t(14;18) NHLs. In
      general, the secondary aberrations were similar in lymphomas of different
      histologic subtypes but with the same primary abnormality, although some
      significant differences were discerned: +3, del(6q), +7, and +18 wee more common
      (P < .01) in intermediate-grade than in high-grade t(8;14) NHLs; monosomy 13
      occurred only in intermediate-grade t(11;14) NHLs (P < .05); and +7 and
      t(8;14)/t(8;22) were more frequent (P < .01 and P< .001, respectively) in high
      grade than in low- and intermediate-grade t(14;18) NHLs.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7579361
TI  - Interphase fluorescence in situ hybridization identifies chromosomal
      abnormalities in plasma cells from patients with monoclonal gammopathy of
      undetermined significance.
AB  - Karyotypic studies in patients with monoclonal gammopathy of undetermined
      significance (MGUS) have been hampered by a low percentage of bone marrow plasma
      cells (BMPC), which are predominantly nonproliferating. By combining
      cytomorphology and interphase fluorescence in situ hybridization (FISH) we
      investigated whether or not chromosomal abnormalities occur in BMPC from patients
      with MGUS. Studying chromosomes 3, 7, 11, and 18, which we found to be frequently
      aneuploid by FISH in multiple myeloma (MM), we observed three hybridization
      signals for one of these chromosomes 3 were most common, occurring in 38.9% of
      patients, followed by gains of chromosomes 11 (25%), 7 (16.7%), and 18 (5.6%)
      Among BMPC, the frequency of aneuploid cells was 18.9% +/- 13.9% (mean +/- SD)
      for chromosome 3, 22.3% +/- 9.2% for chromosome 11, 23.2% +/- 22.0% for
      chromosome 7, and 6.1% +/- 2.3% for chromosome 18. In five patients, chromosomal
      abnormalities were shown to be restricted to BMPC expressing cytoplasmic
      immunoglobulins corresponding to the serum paraprotein. No gain of hybridization
      signals was observed in normal and reactive plasma cells. In one patient with
      MGUS, metaphase cytogenetics revealed one abnormal metaphase with 47, XY, +4, and
      trisomy 4 was also demonstrated in a subpopulation of BMPC by interphase FISH.
      FISH results from patients with MGUS and newly diagnosed MM at stage IA (n = 14)
      indicated that aberrations involving > or = 2 chromosomes occurred significantly
      more often in early stage MM (P < .01). With respect to clinical and laboratory
      features, MGUS patients with and without chromosomal abnormalities were
      indistinguishable. Our results indicate that MGUS already has the chromosomal
      characteristics of a plasma cell malignancy.

PMID- 7579362
TI  - Presence of Epstein-Barr virus and strain type assignment in Argentine childhood
      Hodgkin's disease.
AB  - Epstein-Barr virus (EBV) has been implicated in the etiology of a large number of
      malignancies. Most recently several studies have linked EBV to Hodgkin's disease.
      In this report, formalin-fixed, paraffin-embedded tissues were collected
      retrospectively from 41 children with Hodgkin's disease treated at our hospital.
      Lymph node biopsies were examined for the presence of two virus-encoded latent
      proteins: latent membrane protein (LMP) and Epstein-Barr nuclear antigen-2 (EBNA
      2), in Reed-Sternberg (RS) and Hodgkin (H) cells, by peroxidase immunolabeling.
      Nonisotopic Epstein-Barr encoded RNAs (EBERs) in situ hybridization was also
      performed and positive labeling in malignant cells was detected. Twenty specimens
      were EBER+/LMP+, 2 were EBER+/LMP-, and 19 were EBER-/LMP-. However, none of the
      41 cases expressed EBNA-2. Twenty-two of 41 (54%) cases were EBV positive
      including 2 of 6 with lymphocyte predominance, 19 of 25 with mixed cellularity, 0
      of 9 with nodular sclerosis, and 1 of 1 with lymphocyte depletion. In the age
      range of 2 to 6 years, 14 of 17 (82%) samples were EBV-positive, whereas only 8
      of 24 (33%) samples from the age range of 7 to 15 years contained EBV. (P =
      .004), a two-tailed Fisher's test). In 17 samples, polymerase chain reaction
      amplification was performed using strain specific primers for exon sequences of
      the EBNA-3C gene of EBV. From 12 positive samples, 8 contained EBV-A and 4 EBV-B.
      These results support the hypothesis that EBV contributes to the pathogenesis of
      pediatric Hodgkin's disease, particularly in mixed cellularity Hodgkin's disease
      and in the younger group.

PMID- 7579363
TI  - Analysis of rearranged T-cell receptor beta-chain genes by polymerase chain
      reaction (PCR) DNA sequencing and automated high resolution PCR fragment
      analysis.
AB  - Polymerase chain reaction (PCR)-directed amplification and sequencing of
      rearranged immune genes for identification of clone-specific markers are
      increasingly being used in acute lymphoblastic leukemia (ALL) and non-Hodgkin's
      lymphoma (NHL) patients instead of the time consuming and labor intensive
      Southern analysis. In previous reports, no single common V beta and J beta
      sequence had been identified that allowed reliable amplification of the majority
      of rearranged T-cell antigen receptor (TCR)-beta V-D-J junctions at the DNA level
      because of the relatively large number of possible TCR-beta variable (V beta) and
      joining (J beta) gene segments involved in the rearrangement processes. In the
      present study we designed highly degenerate PCR primers directed against
      conserved sequences of the J beta genes. IN combination with a previously
      published consensus V beta primer, these J beta primers specifically amplify TCR-
      beta V-N(D)N-J junctions from genomic DNA. Using this approach we studied DNA
      extracted from biopsy material of nine patients with T-cell lymphoproliferative
      disorders, one c-ALL patient, and five patients with nonmalignant diseases. T
      cell lines Molt 3, Jurkat, and HM 2 served as monoclonal controls. Individual PCR
      products were sequenced after cloning. The nucleotide sequences of 96 randomly
      chosen recombinant vectors were determined. In the polyclonal controls all
      analyzed clones differed in their TCR-beta V-N(D)N-J junctions. In the T-cell
      lines, in all of the T-cell malignancies, and in the c-ALL, monoclonal PCR
      products could be identified by demonstration of clonally restricted V-N(D)N-J
      junctions. The PCR results were confirmed by automated fluorescence
      quantification and size determination of PCR products after separation in a high
      resolution polyacrylamide gel. The procedure allows rapid and specific
      characterization of clonal TCR-beta rearrangements from genomic DNA and will
      significantly simplify current experimental approaches to identify and to
      quantitate malignant T cells during initial staging and follow-up of T-lineage
      NHL and ALL patients.

PMID- 7579364
TI  - Neutrophils activated by granulocyte-macrophage colony-stimulating factor express
      receptors for interleukin-3 which mediate class II expression.
AB  - Freshly isolated peripheral blood neutrophils, unlike monocytes and eosinophils,
      do not bind interleukin-3 (IL-3) or respond to IL-3). We show that neutrophils
      cultured for 24 hours in granulocyte-macrophage colony-stimulating factor (GM
      CSF) express mRNA for the IL-3 receptor (R) alpha subunit, as shown by RNase
      protection assays, and IL-3R alpha chain protein, as shown by cytometric analysis
      using two different specific monoclonal antibodies. This effect was selective for
      GM-CSF, because granulocyte colony-stimulating factor, tumor necrosis factor
      alpha, interferon-gamma, and IL-1 failed to induce the IL-3 receptor. Saturation
      binding curves with 125I-IL-3 and Scatchard transformation showed the presence of
      about 100 high-affinity and 4,000 low-affinity receptors. Because neutrophils
      have been shown to express human leukocyte antigen (HLA)-DR in response to GM
      CSF, we examined the possibility that IL-3 could augment HLA-DR expression on GM
      CSF-treated cells. We found that neutrophils incubated with 30 ng/mL IL-3 as well
      as 0.1 ng/mL GM-CSF expressed a mean of 2.1-fold higher levels of HLA-DR than
      with GM-CSF alone (P < .005), confirming the signaling competence of the newly
      expressed IL-3R. This increase was seen even at maximal concentrations of GM-CSF
      and IL-3 can have an additive effect on mature human cells. The augmentation of
      HLA-DR by IL-3 was specific because it could be inhibited by a blocking anti-IL
      3R antibody. Expression of class II molecules by neutrophils under these
      conditions may have significance for antigen presentation. These results provide
      further evidence for the role of GM-CSF as an amplification factor in
      inflammation by inducing neutrophil responsiveness to IL-3 produced by T cells or
      mast cells.

PMID- 7579365
TI  - The instability of the membrane skeleton in thalassemic red blood cells.
AB  - The thalassemias are a heterogeneous group of disorders characterized by
      accumulation either of unmatched alpha or beta globin chains. These in turn cause
      the intramedullary and peripheral hemolysis that leads to varying anemia. A
      partial explanation for the hemolysis came our of our studies on material
      properties that showed that beta-thalassemia (beta-thal) intermedia ghosts were
      very rigid but unstable. A clue to this instability came from the observation
      that the spectrin/band 3 ratio was low in red blood cells (RBCs) of
      splenectomized beta-thal intermedia patients. The possible explanations for the
      apparent decrease in spectrin content included deficient or defective spectrin
      synthesis in thalassemic erythroid precursors or globin chain-induced membrane
      changes that lead to spectrin dissociation from the membrane during ghost
      preparation. To explore the latter alternative, samples from different
      thalassemic variants were obtained, ie, beta-thal intermedia, HbE/beta-thal, HbH
      (alpha-thal-1/alpha-thal-2), HbH/Constant Spring (CS), and homozygous HbCS/CS. We
      searched for the presence of spectrin in the first lysate of the standard ghost
      preparation. Normal individuals and patients with autoimmune hemolytic anemia,
      sickle cell anemia, and anemia due to chemotherapy served as controls. Using
      gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, no
      spectrin was detected in identical aliquots of the supernatants of normals and
      these control samples. Varying amounts of spectrin were detected in the first
      lysate supernatants of almost all thalassemic patients. The identification of
      spectrin was confirmed by Western blotting using an affinity-purified,
      monospecific, rabbit polyclonal antispectrin antibody. Relative amounts of
      spectrin detected were as follows in decreasing order: splenectomized beta-thal
      intermedia including HbE/beta-thal; HbCS/CS; nonsplenectomized beta-thal
      intermedia, HbH/CS; and, lastly, HbH. These findings were generally confirmed
      when we used an enzyme-linked immunosorbent assay technique to measure spectrin
      in the first lysate. Subsequent analyses showed that small amounts of actin and
      band 4.1 also appeared in lysates of thalassemic RBCs. Therefore, the three major
      membrane skeletal proteins are, to a varying degree, unstably attached in severe
      thalassemia. From these studies we could postulate that membrane association of
      abnormal or partially oxidized alpha-globin chains has a more deleterious effect
      on the membrane skeleton than do beta-globin chains.

PMID- 7579366
TI  - Platelet storage for transfusion in synthetic media: further optimization of
      ingredients and definition of their roles.
AB  - Currently, most platelet concentrates (PC) are stored for transfusion at 20
      degrees C to 24 degrees C in autologous plasma. There are potential advantages in
      replacing some of this plasma with a synthetic medium. In this study, our major
      goals were to define the optimal ingredients and their concentrations in such a
      medium and to gain insight into the mechanism by which each ingredient confers
      benefit. In addition, we wished to validate a new polyvinyl chloride container
      plasticized with di-n-decyl phthalate (DnDP) for PC storage. PC derived from
      donations of whole blood were stored for 7 days in autologous plasma or a basic
      synthetic medium (BSM) containing 15 mmol/L glucose, 21 mmol/L citrate, and
      physiologic concentrations of salts other than bicarbonate within either the DnDP
      container or a licensed polyolefin container, PL-732. Metabolic events were
      characterized and a panel of in vitro tests were used to monitor platelet quality
      as systematic changes in the BSM were made. Platelet quality was as least as
      good, if not better, after storage in DnDP in comparison to PL-732. pH
      consistently decreased to less than 6.0 because of inadequate buffering of lactic
      acid in BSM alone. However, pH and the in vitro tests were well maintained by
      either the serial addition of bicarbonate (BSM + B) or the addition of at least
      15 mmol/L acetate and 10 mmol/L phosphate (BSM + AP). The benefits of BSM + AP
      were traced to a decrease in lactic acid production by 33% and 19% relative to
      plasma and BSM + B, respectively, and the vigorous oxidation of acetate (0.66 +/-
      0.09 mmol/d/10(12 platelets). The rates of lactate production and acetate
      consumption were similar and the pH during storage correlated with difference
      between the two rates, suggesting that acetate oxidation has an alkalinizing
      effect equivalent on a molar basis to the acidifying effect of production of
      lactate and a hydrogen ion. When pyruvate replaced acetate, it was also
      metabolized vigorously (0.52 +/- 0.06 mmol/d/10(12) platelets). Its presence
      suppressed lactic acid production by 44% relative to BSM + B and allowed
      maintenance of pH and platelet quality similar to what is achieved with acetate.
      The results strongly suggest that the benefit from acetate (or pyruvate) is
      derived from its oxidation and the use of a hydrogen ion during that oxidation.
      For reasons that are not yet clear, the omission of phosphate resulted in pH
      decrease to less than 6.0 in 3 of 9 PC even with acetate present.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7579367
TI  - An analysis of engraftment kinetics as a function of the CD34 content of
      peripheral blood progenitor cell collections in 692 patients after the
      administration of myeloablative chemotherapy.
AB  - The CD34 antigen is expressed by committed and uncommitted hematopoietic
      progenitor cells and is increasingly used to assess stem cell content of
      peripheral blood progenitor cell (PBPC) collections. Quantitative CD34 expression
      in PBPC collections has been suggested to correlate with engraftment kinetics of
      PBPCs infused after myeloablative therapy. We analyzed the engraftment kinetics
      as a function of CD34 content in 692 patients treated with high-dose chemotherapy
      (HDC). Patients had PBPCs collected after cyclophosphamide based mobilization
      chemotherapy with or without recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) until > or = 2.5 x 10(6) CD34+ cells/kg were harvested.
      Measurement of the CD34 content of PBPC collections was performed daily by a
      central reference laboratory using a single technique of CD34 analysis. Forty
      five patients required a second mobilization procedure to achieve > or = 2.5 x
      10(6) CD34+ cells/kg and 15 patients with less than 2.5 x 10(6) CD34+ cells/kg
      available for infusion received HDC. A median of 9.94 x 10(6) CD34+ cells/kg
      (range, 0.5 to 112.6 x 10(6) CD34+ cells/kg) contained in the PBPC collections
      was subsequently infused into patients after the administration of HDC.
      Engraftment was rapid with patients requiring a median of 9 days (range, 5 to 38
      days) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 9 days
      (range, 4 to 53+ days) to achieve a platelet count of > or = 20 x 10(9)/L. A
      clear dose-response relationship was evident between the number of CD34+ cells
      per kilogram infused between the number of CD34+ cells per kilogram infused and
      neutrophil and platelet engraftment kinetics. Factors potentially influencing the
      engraftment kinetics of neutrophil and platelet recovery were examined using a
      Cox regression model. The single most powerful mediator of both platelet (P =
      .0001) and neutrophil (P = .0001) recovery was the CD34 content of the PBPC
      product. Administration of a post-PBPC infusion myeloid growth factor was also
      highly correlated with neutrophil recovery (P = .0001). Patients receiving high
      dose cyclophosphamide, thiotepa, and carboplatin had more rapid platelet recovery
      than patients receiving other regimens (P = .006), and patients requiring 2
      mobilization procedures versus 1 mobilization procedure to achieve > or = 2.5 x
      10(6) CD34+ cells/kg experienced slower platelet recovery (P = .005). Although a
      minimal threshold CD34 dose could not be defined, > or = 5.0 x 10(6) CD34+
      cells/kg appears to be optimal for ensuring rapid neutrophil and platelet
      recovery.

PMID- 7579368
TI  - Autologous progenitor cell transplantation: prior exposure to stem cell-toxic
      drugs determines yield and engraftment of peripheral blood progenitor cell but
      not of bone marrow grafts.
AB  - Agents with stem cell-toxic potential are frequently used for salvage therapy of
      Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many
      patients with relapsed or refractory lymphoma are candidates for autologous
      progenitor cell transplantation, possible toxic effects of salvage chemotherapy
      on progenitor cells must be taken into account. In a retrospective study, we have
      analyzed the influence of a salvage regimen containing the stem cell-toxic drugs
      BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and
      peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other
      factors. Progenitor cells were collected from 96 patients with HD or high-grade
      NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose
      chemotherapy. Compared with patients autografted with BM, hematopoietic recovery
      was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa
      BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting
      colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P
      = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery
      to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L
      (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation
      (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy
      was associated with significantly lower CFU-GM and CD34+ cell yields but had no
      influence on engraftment. Patient age, patient sex, disease activity, or
      chemotherapy other than Dexa-BEAM did not have any prognostic impact.
      Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding
      factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P <
      .0001), and platelet engraftment (P < .0001). BM grafts were not significantly
      affected by previous Dexa-BEAM chemotherapy or any other variable tested.
      However, prognostic factors favoring the use of BM instead of PBPC were not
      identified using joint regression models involving interaction terms between the
      graft type (PBPC or BM) and the explanatory variables investigated. We conclude
      that, in contrast to previous radiotherapy or other chemotherapy, exposure to
      salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is
      a critical factor adversely affecting yields and performance of PBPC grafts.
      Marrow progenitor cells appear to be less sensitive to stem cell-toxic
      chemotherapy. PBPC should be harvested before repeated courses of salvage
      chemotherapy involving stem cell-toxic drugs to preserve the favorable
      repopulation kinetics of PBPC in comparison with BM.

PMID- 7579369
TI  - Late infections after allogeneic bone marrow transplantations: comparison of
      incidence in related and unrelated donor transplant recipients.
AB  - Infectious complications are a major cause of morbidity and mortality after
      allogeneic bone marrow transplantation (BMT). We have evaluated the incidence of
      late infections (beyond day +50) in recipients of related (RD) and unrelated
      donor (URD) allogeneic BMT, factors associated with increased risks of infection,
      and the impact of the late infections on survival. Between 1989 and 1991, 249
      patients received an RD (n = 151) or URD (n = 98) allogeneic BMT at the
      University of Minnesota and all late infections were investigated. Three hundred
      sixty-seven late infectious events developed in 162 patients between 50 days and
      2 years after BMT. The incidence of any late infection was greater in URD versus
      RD recipients (84.7% v 68.2%, respectively; P = .009). In multivariate analysis,
      advanced graft-versus-host disease (GVHD) was significantly associated with late
      infections. The effect of GVHD was apparent only in RD recipients (relative risk
      [RR], 2.29; P = .003), whereas URD recipients, with or without GVHD, had more
      late infections compared with RD recipients without GVHD. Multivariate analysis
      showed that late posttransplantation infections were the dominant independent
      factor associated with increased nonrelapse mortality (RR, 5.5; P = .0001),
      resulting in improved 3-year survival for RD versus URD recipients (49.9% +/- 8%
      v 34.4% +/- 10%; P = .004). In this study, we observed that late infections are
      more frequent in URD recipients, resulting in substantially higher nonrelapse
      mortality. This prolonged period of increased infectious risk in URD recipients
      suggests the need for aggressive surveillance and therapy of late infections and
      perhaps prolonged antibiotic prophylaxis for all URD BMT recipients.

PMID- 7579371
TI  - Sickle cell anemia in septuagenarians.

PMID- 7579370
TI  - Use of unrelated marrow grafts compensates for reduced graft-versus-leukemia
      reactivity after T-cell-depleted allogeneic marrow transplantation for chronic
      myelogenous leukemia.
AB  - The effect of donor/recipient histocompatibility on relapse in patients receiving
      T-cell-depleted (TCD) grafts for chronic myelogenous leukemia (CML) was
      evaluated. Specifically, we sought to determine whether TCD results in an
      attenuation of the graft-versus-leukemia (GVL) effect on recipients of unrelated
      marrow grafts similar to that observed in HLA-identical sibling marrow
      transplantations. This question was addressed by comparative analysis of the
      relapse rates in marrow grafts who otherwise received identical preparative
      regimens and graft-versus-host disease (GVHD) prophylaxis schedules (T-cell
      depletion with T10B9 monoclonal antibody and complement plus posttransplant
      cyclosporine) and by serial molecular analyses using the polymerase chain
      reaction (PCR) to detect the bcr/abl RNA transcript in patients transplanted with
      unrelated donor grafts. Patients transplanted with advanced disease (accelerated
      phase or blast crisis) had equally high relapse rates, regardless of whether they
      received HLA-identical sibling (56%;95% confidence interval [CI], 29% to 82%) or
      unrelated marrow grafts (8%; 95% CI, 0% to 28%) had a significantly lower
      incidence of relapse than did patients transplanted with HLA-identical marrow
      grafts (47%; 95% CI, 23% to 71%; P = .002). Because all patients were similarly
      treated, these data indicate that the lower relapse rate in these unrelated
      patients was caused by an augmented GVL effect that was most likely attributable
      to increased HLA disparity between donor and recipient. The probability of
      developing both acute and chronic GVHD was significantly increased in chronic
      phase recipients of unrelated marrow grafts, suggesting that the enhanced GVL
      effect was at least partly GVHD-associated. The lack of such a finding in
      advanced disease patient receiving unrelated marrow grafts raises the possibility
      that clinically significant GVL effect after TCD marrow transplantation was
      limited and confined to patients with more indolent disease. Serial PCR analyses
      for the presence of the bcr/abl RNA transcript showed that the vast majority of
      patients transplanted in chronic phase with unrelated marrow grafts were
      persistently PCR-negative, indicating that the GVL effect was durable in these
      patients. Most of these patients were observed to become PCR negative within 1 to
      2 months after transplantation, showing that early eradication of leukemia was
      possible with TCD marrow grafts. This study shows that the use of unrelated
      marrow grafts compensates for reduced GVL reactivity associated with TCD in
      patients transplanted for CML. Furthermore, these data indicate that, in selected
      patient populations with CML, TCD can be used to reduce GVHD without a
      commensurate compromise in the GVL effect.

PMID- 7579372
TI  - Oxygen inhalation in nonhypoxic sickle cell patients during vaso-occlusive
      crisis.

PMID- 7579373
TI  - The polymorphonuclear neutrophil Fc gamma RIIIb deficiency is more frequent than
      hitherto assumed.

PMID- 7579374
TI  - Circulating CD19+ blood cell levels in myeloma. ECOG Myeloma Clinical Trials
      Laboratory Study Group.

PMID- 7579376
TI  - American Society of Hematology 37th annual meeting. Seattle, Washington, December
      1-5, 1995. Abstracts.

PMID- 7579375
TI  - Human myeloma cell lines as a tool for studying the biology of multiple myeloma:
      a reappraisal 18 years after.

PMID- 7579377
TI  - Treatment of primary central nervous system lymphoma: still more questions than
      answers.

PMID- 7579378
TI  - Developmental biology of hematopoiesis.
AB  - The cellular and environmental regulation of hematopoiesis has been generally
      conserved throughout vertebrate evolution, although subtle species differences
      exist. The factors that regulate hematopoietic stem cell homeostasis may closely
      resemble the inducers of embryonic patterning, rather than the factors that
      stimulate hematopoietic cell proliferation and differentiation. Comparative study
      of embryonic hematopoiesis in lower vertebrates can generate testable hypotheses
      that similar mechanisms occur during hematopoiesis in higher species.

PMID- 7579379
TI  - Posttransplantation lymphoproliferative gingival disease.

PMID- 7579381
TI  - Deletion of cyclin-dependent kinase 4 inhibitor genes P15 and P16 in non
      Hodgkin's lymphoma.
AB  - B-cell non-Hodgkin's lymphoma (NHL) is a heterogeneous lymphoid malignancy
      consisting of several histologic types. Alterations in proto-oncogenes caused by
      reciprocal chromosome translocations have been implicated in the etiology of
      specific histologic groups. In this study, we examined the contribution of the
      cell cycle inhibitor genes P15, P16, and P18 to pathogenesis in a large panel of
      209 cytogenetically characterized B-cell NHL tumors representing varied
      histologic groups. We identified the homozygous deletion of P15 and P16 genes in
      13 tumors from 12 patients, all belonging to diffuse large-cell histology; 10 had
      this diagnosis made on presentation, 1 had transformed from small lymphocytic
      lymphoma, and 1 had transformed from Hodgkin's disease. Tumor-specific point
      mutations were not identified in the coding regions of these genes.
      Cytogenetically, chromosome 9p was normal in all but one tumor. On the other
      hand, eight tumors hemizygous for 9p by cytogenetic analysis showed wild-type
      configuration of these genes. Our study, therefore, indicates that deletion of
      P15 and P16 occurs in about 15% of diffuse large-cell NHL and is not usually
      detected by cytogenetic analysis. P18 was wild-type in all tumors including the
      13 tumors hemizygous for 1p.

PMID- 7579380
TI  - p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with
      t(11;14)(q13;q32).
AB  - The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the
      Ig heavy chain locus, has been associated with an uncommon subtype of non
      Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular
      marker that serves as an indicator of tumor progression or clinical prognosis has
      been described for NHLs with this translocation. We examined a panel of NHLs with
      t(11;14) for overexpression of p53 and correlated the results with single-strand
      conformation polymorphism (SSCP) analysis, karyotypic features, and clinical
      course. NHLs with t(11;14) were identified from 30 patients. The diagnosis was
      MCL for 23 of 30, small lymphocytic lymphoma for 4 of 30, and diffuse large-cell
      lymphoma for 3 of 30 cases. The results of immunohistochemistry analysis using a
      monoclonal anti-p53 antibody on paraffin-embedded specimens were compared with
      the SSCP data, the tumor karyotypes, and clinical course of each patient. DNA
      sequencing of exons was performed on cases that showed conformational changes by
      SSCP analysis. NHLs from 5 of 23 patients with MCL were positive for p53
      overexpression. Deletions of chromosome 17p were identified in 2 of 30 cases,
      both of which were MCLs showing p53 overexpression. Two of the five MCLs with p53
      overexpression showed evidence for TP53 mutations. None of the 18 MCLs negative
      for p53 overexpression showed conformational changes by SSCP. For these 18
      patients with MCLs that did not overexpress p53, the median survival was 63
      months, compared with 12 months for the 5 patients with MCLs positive for p53
      overexpression (P < .001). These results suggest that p53 overexpression in MCL
      with t(11;14)(q13;q32) may serve as a marker of poor prognosis.

PMID- 7579382
TI  - Evidence for malignant transformation in acute myeloid leukemia at the level of
      early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations.
AB  - Acute myeloid leukemia (AML) is a heterogenous disease according to morphology,
      immunophenotype, and genetics. The retained capacity of differentiation is the
      basis for the phenotypic classification of the bulk population of leukemic blasts
      and the identification of distinct subpopulations. Within the hierarchy of
      hematopoietic development and differentiation it is still unknown at which stage
      the malignant transformation occurs. It was our aim to analyze the potential
      involvement of cells with the immunophenotype of pluripotent stem cells in the
      leukemic process by the use of cytogenetic and cell sorting techniques.
      Cytogenetic analyses of bone marrow aspirates were performed in 13 patients with
      AML (11 de novo and 2 secondary) and showed karyotype abnormalities in 10 cases
      [2q+, +4, 6p, t(6:9), 7, +8 in 1 patient each and inv(16) in 4 patients each].
      Aliquots of the samples were fractionated by fluorescence-activated cell sorting
      of CD34+ cells. Two subpopulations, CD34+/CD38- (early hematopoietic stem cells)
      and CD34+/CD38+ (more mature progenitor cells), were screened for karyotype
      aberations as a marker for leukemic cells. Clonal abnormalities and evaluable
      metaphases were found in 8 highly purified CD34+/CD38- populations and in 9 of
      the CD34+/CD38- specimens, respectively. In the majority of cases (CD34+/CD38-, 6
      of 8 informative samples; CD34+/CD38+, 5 of 9 informative samples), the highly
      purified CD34+ specimens also contained cytogenetically normal cells. Secondary,
      progression-associated chromosomal changes (+8, 12) were identified in the
      CD34+/CD38- cells of 2 patients. We conclude that clonal karyotypic abnormalities
      are frequently found in the stem cell-like (CD34+/CD38-) and more mature
      (CD34+/CD38+) populations of patients with AML, irrespective of the phenotype of
      the bulk population of leukemic blasts and of the primary or secondary character
      of the leukemia. Our data suggest that, in AML, malignant transformation as well
      as disease progression may occur at the level of CD34+/CD38- cells with
      multilineage potential.

PMID- 7579383
TI  - A phase I study of sequential versus concurrent interleukin-3 and granulocyte
      macrophage colony-stimulating factor in advanced breast cancer patients treated
      with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide)
      chemotherapy.
AB  - Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intensive
      chemotherapy for advanced breast cancer. In this phase I study, we have studied
      the hematologic toxicity associated with sequential interleukin-3 (IL-3) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim)
      administration after multiple cycles of FLAC (5-fluorouracil, leucovorin,
      doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent
      cytokine administration or to each cytokine administered alone. Ninety-three
      patients with advanced breast cancer were treated with five cycles of FLAC
      chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF
      administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or
      schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent
      administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated
      with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg)
      administered subcutaneously for each schedule of cytokine administration. The GM
      CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM-CSF
      (schedule B) was associated with higher platelet nadirs, shorter durations of
      platelet counts less than 50,000/microL, and the need for fewer platelet
      transfusions over five cycles of FLAC chemotherapy compared with concurrent
      cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL
      3 and GM-CSF was associated with unexpected platelet toxicity. The duration of
      granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone
      compared with each of the GM-CSF-containing cytokine regimens. Although no cycle
      1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was
      well tolerated over multiple cycles of therapy and is recommended for future
      studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF
      with IL-3 administered for 9 days before beginning GM-CSF may be superior to
      shorter durations of IL-3 administered sequentially with GM-CSF, to concurrent IL
      3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the
      cumulative hematologic toxicity associated with multiple cycles of FLAC
      chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.

PMID- 7579384
TI  - The C5R protocol: a regimen of high-dose chemotherapy and radiotherapy in primary
      cerebral non-Hodgkin's lymphoma of patients with no known cause of
      immunosuppression.
AB  - In most reported series, less than 20% of patients with primary cerebral non
      Hodgkin's lymphoma (PCL) and no known cause of immunodepression are alive and
      disease-free 5 years after the initial diagnosis. Whether chemotherapy improves
      the outcome of these patients remains unclear. We report a pilot study of a
      protocol (C5R) with 5 courses of chemotherapy followed by cranial radiotherapy in
      25 adult patients with PCL and no known cause of immunodepression. The median age
      was 51 years (range, 16 to 70 years) and the median performance status was 2
      (range, 1 to 4) in this series. Fourteen patients (56%) achieved a complete
      response and 4 (16%) achieved a partial response 1 month after the completion of
      the treatment. Four patients died in the first month of treatment because of
      progression (n = 1) or toxicity (n = 3). In 3 patients, the treatment could not
      be performed because of patient refusal (n = 1) or severe infections (n = 2).
      Myelosuppression was the most frequent side effect; febrile neutropenia occurred
      in 96%, 89%, 69%, and 74% of the patients after the second, third, fourth, and
      fifth courses of chemotherapy, respectively. Grade 4 thrombocytopenia occurred in
      20% of the patients. With a median follow-up of 24 months, the projected survival
      of the group at 2 and 5 years is 70% and 56%, respectively. The 4 early deaths
      occurred in the subgroup of 6 patients greater than 60 years of age with an
      international prognostic index (IPI) greater than 3. In the 19 remaining patients
      (76% of this series) less than 61 years of age or with an IPI less than 4, the
      projected overall survival at 2 and 5 years is 88% and 70%, respectively. The C5R
      protocol is a highly efficient regimen in nonimmunosuppressed patients with PCL
      less than 61 years of age or with an IPI less than 4.

PMID- 7579385
TI  - Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic
      progenitor cells: increase of early hematopoietic progenitor cells in TNF
      receptor p55-deficient mice in vivo and potent inhibition of progenitor cell
      proliferation by TNF alpha in vitro.
AB  - Murine bone marrow cells with lineage phenotypes (Lin)-Sca-1+c-kit+ and Lin-Sca-1
      c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed
      hematopoietic progenitor cells, respectively. The number of Lin-Sca-1+c-kit+ HSCs
      in bone marrow was significantly increased in tumor necrosis factor (TNF)
      receptor p55-deficient (TNF-R55-1-) mice compared with the TNF-R55+/+ wild-type
      mice without a marked change in bone marrow cellularity. In both the
      methylcellulose culture and a single-cell proliferation assay, mouse TNF alpha
      (mTNF alpha) inhibited in vitro the proliferation of wild-type mouse-derived Lin
      Sca-1+c-kit+ cells in response to a combination of multiple growth factors. The
      same is true for that of Lin-Sca-1+c-kit+ cells stimulated with granulocyte
      colony-stimulating factor (G-CSF) plus stem cell factor (SCF). Moreover, mTNF
      alpha significantly arrested the entry into S-phase from G0/G1 phase of Lin-Sca
      1+c-kit+ cells stimulated with multiple growth factors and Lin-Sca-1-c-kit+ cells
      stimulated with G-CSF plus SCF. In contrast, mTNF alpha failed to affect the
      growth and cell cycle progression of Lin-Sca-1+c-kit+ cells and Lin-Sca-1-c-kit+
      cells that were obtained from TNF-R55-deficient mice. These data suggest that TNF
      may be an important physiologic regulator of hematopoiesis and that TNF-R55 may
      be essentially involved in TNF-mediated inhibition of the growth of both
      primitive stem and more committed progenitor cells.

PMID- 7579386
TI  - Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently
      in aplastic anemia.
AB  - We evaluated the methylation status of the X-linked gene phosphoglycerate kinase
      (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in
      acquired aplastic anemia (AA). A total of 30 females were suitable for clonal
      analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells
      using a polymerase chain reaction-based procedure in 24 patients and Southern
      blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation
      pattern. However, in 4 patients, analysis of constitutional DNA suggested a
      skewed methylation pattern and 2 further cases had to be excluded because of the
      lack of an appropriate control. A truly clonal pattern was thus established in 4
      of 30 (13%) patients. In 7 patients who later developed clonal disorders of
      hematopoiesis, X-inactivation analysis did not predict this event in any case. In
      patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no
      correlation between the proportion of phosphatidylinositol glycan anchored
      protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation
      pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10
      patients with a deficiency in PIG-AP in the cell population under study, but
      sorting of nucleated cells on the basis of PIG-AP expression showed the clonal
      nature of PIG-AP-deficient cells. We conclude that the majority of patients with
      AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor
      clonal populations, such as PIG-AP-deficient cells, may not be detected unless
      sorted cell populations are separately analyzed.

PMID- 7579388
TI  - Transforming growth factor-beta potently inhibits the viability-promoting
      activity of stem cell factor and other cytokines and induces apoptosis of
      primitive murine hematopoietic progenitor cells.
AB  - In contrast with the extensively characterized effects of transforming growth
      factor-beta (TGF-beta) on proliferation and differentiation of hematopoietic
      progenitors, little is known about the effects of TGF-beta on viability of normal
      hematopoietic progenitors. In the present report, we demonstrate that TGF-beta
      potently counteracts hematopoietic growth factor (HGF)-induced survival of
      individually cultured primitive Lin-Sca-1+ bone marrow progenitors. Specifically,
      74% of single Lin-Sca-1+ cells cultured for 40 hours in the presence of stem cell
      factor (SCF) survived, whereas only 16% survived in the presence of SCF plus TGF
      beta. Similarly, the enhanced survival of primitive hematopoietic progenitors in
      response to granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1, IL
      6, or IL-11 was also potently opposed by TGF-beta. Furthermore, it is
      demonstrated that neutralization of endogenous TGF-beta present in the cultures
      enhances survival of Lin-Sca-1+ progenitors in the absence, as well as in the
      presence, of HGFs such as SCF and IL-6. The reduced HGF-induced survival of
      primitive hematopoietic progenitors in the presence of TGF-beta was associated
      with increased apoptosis, as detected by an in situ terminal deoxynucleotidyl
      transferase (TdT) assay. After 16 hours of incubation in the absence of HGFs, 61%
      +/- 6% of the hematopoietic progenitors had DNA strand breaks characteristic of
      apoptosis. The presence of SCF reduced the frequency of apoptic cells to 27% +/-
      5%, whereas 55% +/- 3% of the cells had signs of apoptosis in the presence of SCF
      plus TGF-beta.

PMID- 7579387
TI  - Colony-stimulating factor 1-induced STAT1 and STAT3 activation is accompanied by
      phosphorylation of Tyk2 in macrophages and Tyk2 and JAK1 in fibroblasts.
AB  - Colony-stimulating factor 1 (CSF-1) causes the activation of STAT1 and STAT3
      transcription factors in bone marrow macrophages (BMM), in the macrophage cell
      line BAC1.2F5, and in fibroblasts that express the wild-type receptor for CSF-1.
      Fibroblasts expressing a mutant receptor in which the tyrosine 809 is replaced
      with phenylalanine do not activate STAT proteins in response to CSF-1. The
      activation of the STAT proteins in BMM is accompanied by tyrosine phosphorylation
      of Tyk2. In fibroblasts, the activation of the STAT proteins is accompanied by
      tyrosine phosphorylation of Tyk2 and JAK1. We propose that these JAK kinases are
      subjected to very rapid phosphorylation in response to CSF-1, followed by rapid
      dephosphorylation. Furthermore, we propose that kinases other than JAK kinase may
      be involved in the phosphorylation of the STAT proteins in response to CSF-1.

PMID- 7579389
TI  - Arachidonic acid induces c-jun gene expression in stromal cells stimulated by
      interleukin-1 and tumor necrosis factor-alpha: evidence for a tyrosine-kinase
      dependent process.
AB  - We have previously shown that granulocyte-macrophage colony-stimulating factor
      (GM-CSF) gene expression induced by interleukin-1 (IL-1) and tumor necrosis
      factor-alpha (TNF-alpha) in the murine stromal cell line +/+.1-LDA 11 involves
      activation of phospholipase A2 (PLA2). Furthermore, induction of GM-CSF gene
      expression due to release of arachidonic acid as a result of PLA2 activation was
      mediated by the transcriptional factor c-jun. In the present study, we have
      investigated the potential mechanism involved in the induction of c-jun gene
      expression by arachidonic acid. Arachidonic acid induced transcription of c-jun
      mRNA. Downregulation of protein kinase C (PKC) by chronic exposure of stromal
      cells to the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 400
      nmol/L) did not effect c-jun expression induced by arachidonate. Moreover,
      pretreatment of cells with the PKC inhibitor, calphostin C (1 mumol/L), caused a
      marked decrease of c-jun expression induced by TPA, but had no influence on c-jun
      expression induced by arachidonate. To explore the hypothesis that a tyrosine
      kinase signalling pathway, independent of PKC activation, was involved in
      arachidonate-induced c-jun expression, stromal cells were pretreated with the
      protein tyrosine kinase inhibitor, genistein, before challenge with arachidonic
      acid. Arachidonate 50 mumol/L)-induced c-jun expression was inhibited, in a dose-
      and time-dependent manner, by genistein. Genistein similarly inhibited c-jun
      expression in stromal cells exposed to IL-1 (500 U/mL) plus TNF-alpha (500 U/mL).
      The potential role of a tyrosine kinase pathway in arachidonate-mediated c-jun
      expression was further investigated by assaying the tyrosine kinase activity of
      cells challenged with arachidonic acid, IL-1, and TNF-alpha. Exposure of stromal
      cells to arachidonic acid induced a 2.1-fold increase in intracellular tyrosine
      kinase activity determined by phosphorylation of the synthetic peptide, raytide,
      in the presence of [gamma-32P]-ATP. Similarly, IL-1 and TNF-alpha induced 1.7-
      and 2.4-fold increases in tyrosine protein kinase activity, respectively. The
      effect of arachidonic acid on tyrosine kinase activity was inhibited by genistein
      and was enhanced by sodium vanadate. The increase of protein tyrosine kinase
      activity detected in arachidonate-stimulated cells was associated, in a dose- and
      time-dependent fashion, with tyrosine phosphorylation of 240-, 40-, and 29-kD
      substrates. These results are consistent with the hypothesis that a tyrosine
      phosphorylation process is triggered by arachidonate as an early event in the
      signalling pathway that leads to increased expression of c-jun.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7579390
TI  - Differentiation-associated changes in CD44 isoform expression during normal
      hematopoiesis and their alteration in chronic myeloid leukemia.
AB  - CD44 is a widely expressed, multifunctional, cell-surface glycoprotein that has
      been implicated in the regulation of normal hematopoiesis. In addition,
      expression of particular isoforms of CD44 has been associated with malignant
      transformation and/or the acquisition of metastatic potential. In this study, we
      used two recently developed monoclonal anti-CD44 antibodies, one reactive with an
      epitope shared by many CD44 isoforms and the other with an epitope unique to CD44
      isoforms containing amino acids encoded by the alternatively spliced exon v10, to
      compare the expression of CD44 on primitive hematopoietic cells from the marrow
      of normal individuals and their neoplastic counterparts present in the peripheral
      blood of patients with chronic myeloid leukemia (CML). Multiparameter
      fluorescence-activated cell sorter (FACS) analysis and cell sorting studies
      showed that CD44 is normally expressed at high to very high levels on both long
      term culture-initiating cells (LTC-IC) and granulopoietic colony-forming cells
      (granulocyte-macrophage colony-forming units [CFU-GM]). In contrast, primitive
      erythropoietic progenitors (burst-forming units-erythroid [BFU-E]) in normal
      marrow were more homogeneous in their expression of CD44, and very few (less than
      5%) showed the very high levels of CD44 seen on 20% to 25% of LTC-IC and CFU-GM.
      Antibody staining showed the expression of exon v10-containing CD44 isoforms to
      be restricted to a small subpopulation (4% to 8%) of morphologically recognizable
      mature (CD34-) myeloid cells within the light-density fraction of normal marrow
      cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed
      the presence of two exon v10-containing mRNA species. In CML, a significantly
      greater proportion of the circulating neoplastic CFU-GM expressed very high
      levels of CD44, and these CFU-GM were accompanied by an increased number of light
      density v10+ cells, including some that coexpressed CD34. Nonmalignant
      hematopoietic progenitors mobilized by prior chemotherapy and growth factor
      treatment of patients with Hodgkin's disease or acute myeloid leukemia in
      remission showed no changes in CD44 expression relative to normal marrow
      progenitors. These results provide evidence of early differentiation-associated
      changes in CD44 expression during normal hematopoiesis in vivo that may be
      deregulated in the neoplastic clone of patients with CML.

PMID- 7579391
TI  - The kinetics of murine hematopoietic stem cells in vivo in response to prolonged
      increased mature blood cell production induced by granulocyte colony-stimulating
      factor.
AB  - Because of the complexity of appropriate stem cell assays, little information on
      the in vivo regulation of murine stem cell biology or stemmatopoiesis is
      available. It is unknown whether and how in vivo the primitive hematopoietic stem
      cell compartment is affected during a continued increased production of mature
      blood cells. In this study, we present data showing that prolonged (3 weeks)
      administration of granulocyte colony-stimulating factor (G-CSF), which is a major
      regulator of mature granulocyte production, has a substantial impact on both the
      size and the location of various stem cell subset pools in mice. We have used the
      novel cobblestone area forming cell (CAFC) assay to assess the effects of G-CSF
      on the stem cell compartment (CAFC days 7, 14, 21, and 28). In marrow, in which
      normally 99% of the total number of stem cells can be found, G-CSF induced a
      severe depletion of particularly the most primitive stem cells to 5% to 10% of
      normal values. The response after 7 days of G-CSF treatment was an increased
      amplification between CAFC day 14 and 7. However, this response occurred at the
      expense of the number of CAFC day 14. It is likely that the resulting gap of CAFC
      day 14 cell numbers was subsequently replenished from the more primitive CAFC day
      21 and 28 compartments, because these cell numbers remained low during the entire
      treatment period. In the spleen, the number of stem cells increased, likely
      caused by a migration from the marrow via the blood, leading to an accumulation
      in the spleen. The increased number of stem cells in the spleen overcompensated
      for the loss in the marrow. When total body (marrow and spleen) stem cell numbers
      were calculated, it appeared that a continued increased production of mature
      granulocytes resulted in the establishment of a higher, new steady state of the
      stem cell compartment; most committed stem cells (CAFC day 7) were increased
      threefold, CAFC day 14 were increased 2.3-fold, CAFC-day 21 were increased 1.8
      fold, and the most primitive stem cells evaluated, CAFC day 28, were not
      different from normal, although now 95% of these cells were located in the
      spleen. Four weeks after discontinuation of the G-CSF treatment, the stem cell
      reserve in the spleen had returned to a normal level, whereas stem cell numbers
      in marrow had recovered to values above normal. This study shows that the
      primitive stem cell compartment is seriously perturbed during an increased
      stimulation of the production of mature blood cells.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7579393
TI  - Regulation of alpha 2 integrin gene expression in cells with megakaryocytic
      features: a common theme of three necessary elements.
AB  - The alpha 2 beta 1 integrin mediates interactions between cells and the
      extracellular matrix molecules, collagen and/or laminin. The alpha 2 beta 1
      integrin is expressed in a variety of cell types, but in cells of hematopoietic
      lineage, expression is restricted to megakaryocytes and platelets. Increased
      expression of the alpha 2 beta 1 integrin during megakaryocytic differentiation
      is a consequence of transcriptional activation of the alpha 2 gene. We have begun
      to characterize the role of the 5' flanking region of the alpha 2 integrin gene
      in regulating expression during megakaryocyte differentiation. A 5-kb fragment of
      the 5' region directs both cell type and differentiation-dependent expression of
      a reporter gene in the pluripotent hematopoietic K562 cells upon megakaryocytic
      differentiation and in the megakaryocytic cell line, Dami. Analysis of a series
      of 5' deletion mutants indicates that expression of the alpha 2 integrin gene in
      cells with megakaryocytic features requires a core promoter region, a silencer
      region, and megakaryocytic enhancers in the distal 5' end. The organization of
      these three distinct regulatory regions of the alpha 2 promoter/enhancer suggests
      a common theme for megakaryocytic gene regulation shared with other megakaryocyte
      specific proteins, including alpha IIb integrin subunit and platelet factor 4.

PMID- 7579392
TI  - Retroviral-mediated gene expression in human myelomonocytic cells: a comparison
      of hematopoietic cell promoters to viral promoters.
AB  - Gene transfer into human hematopoietic stem cells with expression targeted to the
      maturing myelomonocytic progeny has applications for gene therapy of genetic
      diseases affecting granulocytes and macrophages. We hypothesized that promoters
      of myeloid-specific genes that are upregulated with myelomonocytic
      differentiation would also upregulate expression of an exogenous gene in a
      retroviral vector. Moloney murine leukemia virus (MoMuLV)-based retroviral
      vectors using promoters from hematopoietic genes (CD11b, CD18, and CD34) were
      compared with vectors with viral promoters (MoMuLV long terminal repeat [LTR],
      cytomegalovirus [CMV], and simian virus 40 [SV40]). Human glucocerebrosidase (GC)
      cDNA was the reporter gene. HL60 cells were transduced with these vectors and
      vector-derived GC activity was compared in undifferentiated HL-60 cells and the
      same cells differentiated into granulocytes using dimethyl sulfoxide or
      monocyte/macrophages using phorbol myristate acetate. In undifferentiated HL-60
      cells, vector-derived GC activity was the highest when it was controlled by the
      MoMuLV LTR. In HL-60 cells differentiated into granulocytes, vector-derived GC
      activity transcribed from the CD11b, MoMuLV LTR, and CMV promoters was equivalent
      to 1.7, 1.5, and 1.5 times the normal endogenous GC activity, respectively, and
      0.8, 2.0, and 3.6 times the normal GC activity, respectively, in those
      differentiated into macrophages. With granulocytic differentiation, the CD11b
      promoter showed maximal induction in GC activity (8-fold); with macrophage
      differentiation, the CD11b promoter showed a fourfold induction in GC expression.
      The CD11b promoter also generated significant levels of GC activity in the
      myelomonocytic progeny of transduced CD34+ cells. Expression from the CD11b
      promoter, unlike that from the CMV or the MoMuLV LTR promoters, was relatively
      myelomonocyte-specific, with minimal expression observed in Jurkat T cells or
      HeLa carcinoma cells. The induction of expression from the CD11b promoter with
      differentiation in HL-60 cells correlates with the developmental regulation of
      the CD11b gene. Retroviral vectors using the CD11b promoter have potential
      utility for gene therapy of disorders affecting the myelomonocytic lineage.

PMID- 7579394
TI  - Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A
      patients.
AB  - The molecular characterization of the mutations in hemophilia A patients is
      hampered by the large size of the factor VIII gene and the great heterogeneity of
      mutations. In this study, we have performed a protocol involving multiplex
      polymerase chain reaction in which 19 exons were amplified in four different
      combinations followed by nonradioactive single-strand conformational polymorphism
      (SSCP) to screen for mutations. Southern blotting was used to detect inversion of
      the factor VIII gene resulting from recombination between copies of the gene A
      (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric
      region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21
      with mild-to-moderate disease) were studied. The inversion of factor VIII
      occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed
      a large extra band in addition to the three bands observed after Southern
      blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was
      detected in 85% and 50% of the patients affected by mild-to-moderate and severe
      disease, respectively. Sixteen different mutations were identified. Eleven
      mutations were novel and comprised 9 point mutations and 2 small deletions. This
      study shows that the methodology used is safe and rapid and has potential for
      detecting almost all of the genetic defects of the studied hemophilia A patients.

PMID- 7579395
TI  - Determinants of plasma factor VIIa levels in humans.
AB  - Several enzymes can activate factor VII in vitro, but the protease responsible
      for generating factor VIIa in vivo has not been determined. Using recombinant
      tissue factor that has undergone a COOH-terminal truncation, a sensitive
      functional assay has been established for measuring plasma factor VIIa levels. To
      evaluate the mechanism responsible for the generation of factor VIIa in vivo, we
      measured the levels of this enzyme after administering purified concentrates of
      factor IX and factor VIII to patients with severe deficiencies of these clotting
      factors. In patients with hemophilia B, factor VIIa levels were initially reduced
      to 0.5 +/- 0.1 ng/mL and gradually increased to normal after infusing 100 U/kg of
      body weight (BW) of factor IX. Despite these increases, there were no significant
      changes in the generation of factor Xa or thrombin. In patients with hemophilia
      A, only a slight reduction in factor VIIa levels (2.5 +/- 1.3 ng/mL) was observed
      as compared with controls (3.3 +/- 1.1 ng/mL) and no significant changes were
      observed after factor VIII levels were normalized. The administration of
      recombinant factor VIIa (10 micrograms/kg BW) to patients with factor VII
      deficiency increased the mean circulating level of the enzyme to 118 ng/mL, but
      this only resulted in normalization of the levels of the activation peptides of
      factor IX and factor X. The above data indicate that factor IXa is primarily
      responsible for the basal levels of free factor VIIa generated in vivo (ie, in
      the absence of thrombosis or provocative stimuli) and that changes in the plasma
      concentrations of free factor VIIa in the blood do not necessarily lead to
      alterations in the extent of factor X activation.

PMID- 7579396
TI  - The factor V B-domain provides two functions to facilitate thrombin cleavage and
      release of the light chain.
AB  - Blood coagulation factors V and VIII are homologous proteins that have the domain
      organization A1-A2-B-A3-C1-C2. Upon thrombin activation, the B-domains of both
      molecules are released. Previous studies on factor VIII showed that the B-domain
      was not required for thrombin cleavage or activity. In contrast, deletion of the
      factor V B-domain (residues 709 to 1545) yielded a molecule with sevenfold
      reduced procoagulant activity that was not cleaved by thrombin. However, this
      factor V B-domain deletion molecule was activated by factor Xa, although the fold
      activation was 85% that of wild-type factor V. Thrombin cleavage of factor V
      occurs initially after residue 709 and subsequently after residues 1018 and 1545.
      The requirement for thrombin cleavage within the B-domain at residue 1018 was
      evaluated by mutagenesis of Arg1018 to Ile. In the resultant R1018I mutant, the
      rate of thrombin activation and appearance of maximal cofactor activity was
      delayed and was consistent with delayed cleavage of the light chain at residue
      1545. In contrast, the rate of factor Xa activation in the R1018I mutant was not
      altered. This finding suggests that thrombin cleavage at 1018 facilitates
      subsequent thrombin cleavage at 1545. Further mutagenesis was used to study the
      requirement for sequences within the factor V B-domain for thrombin cleavage at
      residue 1545. Whereas the factor V deletion molecule removing residues 709 to
      1545 was not cleaved by thrombin, a smaller B-domain deletion molecule (residues
      709 to 1476) containing an acidic amino acid-rich region (residues 1490 to 1520)
      was effectively cleaved by thrombin. These results show that residues 1476 to
      1545, which contain an acidic amino acid-rich region, were required for thrombin
      cleavage of the light chain. Introduction of an acidic amino acid-rich region
      from factor VIII (residues 337 to 372) into the factor V 709 to 1545 deletion
      also restored thrombin cleavage of the light chain. In contrast, similar
      replacement with the acidic region from the factor VIII light chain (residues
      1649 to 1689) was significantly less effective in promoting thrombin cleavage of
      the light chain. This finding suggests that the different acidic regions in
      factors V and VIII are not functionally equivalent in their interaction with
      thrombin.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7579397
TI  - Feedback activation of factor XI by thrombin in plasma results in additional
      formation of thrombin that protects fibrin clots from fibrinolysis.
AB  - Recently, an alternative pathway for factor XI activation has been described in
      which factor XI is activated by thrombin. Patients with a factor XI deficiency
      bleed mostly from tissues with high local fibrinolytic activity. Therefore, the
      role of thrombin-mediated factor XI activation in both fibrin formation and
      fibrinolysis was studied in a plasma system. Clotting was induced by the addition
      of tissue factor or thrombin to recalcified plasma in the presence or absence of
      tissue-type plasminogen activator, after which clot formation and lysis were
      measured using turbidimetry. Thrombin-mediated activation of factor XI was found
      to take place in plasma under physiologic conditions in the absence of a dextran
      sulfate-like cofactor. At high tissue factor concentrations, no effect of factor
      XI was seen on the rate of fibrin formation. Decreasing amounts of tissue factor
      resulted in a gradually increasing contribution of factor XI to the rate of
      fibrin formation. In addition, thrombin-mediated factor XI activation resulted in
      an inhibition of tissue-type plasminogen activator-induced lysis of the clot.
      This inhibition occurred even at tissue factor concentrations at which no effect
      of factor XI was observed on fibrin formation. Trace amounts of activated factor
      XI (1.25 pmol/L, representing 0.01% activation) were capable of completely
      inhibiting fibrinolysis in our system. The inhibitory effect was found to be
      mediated by thrombin that is additionally generated in a factor XI-dependent
      manner via the intrinsic pathway and is capable of protecting the clot against
      lysis. We also observed that formation of additional thrombin continued after the
      clot had been formed. We conclude that thrombin-mediated factor XI activation can
      take place in plasma. The presence of factor XI during coagulation results in the
      formation of additional thrombin within the clot capable of protecting this clot
      from fibrinolytic attack. The large amounts of thrombin that are formed by the
      intrinsic pathway via factor XI may play an important role in the procoagulant
      and thrombogenic state of clots and may therefore have important clinical and
      therapeutic implications.

PMID- 7579398
TI  - Idiotype-reactive T-cell subsets and tumor load in monoclonal gammopathies.
AB  - The presence of idiotype-reactive T-cell subsets and their relation to the tumor
      load were analyzed in 9 patients with monoclonal gammopathy of undetermined
      significance (MGUS), in 12 patients with multiple myeloma (MM) clinical stage I,
      and in 9 patients with MM stage II/III. An enzyme-linked immunospot assay was
      used to identify interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, or IL-4
      secreting T cells after stimulation by F(ab')2 fragments of monoclonal IgG. The
      response to autologous IgG was significantly higher than that induced by isotypic
      monoclonal IgG. Comparable results were obtained in a proliferation assay (3H
      thymidine incorporation). A total of 8 of 9 patients with MGUS, 7 of 12 patients
      with MM stage I, and 3 of 9 with MM stage II/III had T cells secreting IFN-gamma
      and/or IL-2 (T helper [Th1] type-1 cells), whereas cells secreting both Th1 and
      Th2 or Th0 types of cytokines were more frequent in patients with MM,
      particularly in those with MM stage II/III. The number and frequency of Th1-type
      cells were significantly higher in MGUS patients as compared with those of MM
      stage II/III. The results indicate that idiotype-reactive T cells of the Th1 and
      Th2 or Th0 subsets were present in MGs and might provide indirect evidence that
      idiotype-reactive Th1-type cells may have a regulatory impact on the human tumor
      B cells.

PMID- 7579399
TI  - The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in
      normal and neoplastic T-lineage lymphocytes.
AB  - The TCF-1 gene encodes a putative transcription factor with affinity for a
      sequence motif occurring in a number of T-cell enhancers. TCF-1 mRNA was
      originally found to be expressed in a T cell-specific fashion within a set of
      human and mouse cell lines. In contrast, expression reportedly occurs in multiple
      nonlymphoid tissues during murine embryogenesis. We have now raised a monoclonal
      antibody to document expression and biochemistry of the human TCF-1 protein. As
      expected, the TCF-1 protein was detectable only in cell lines of T lineage. Its
      expression was always restricted to the nucleus. Immunohistochemistry on a panel
      of human tissues revealed that the TCF-1 protein was found exclusively in
      thymocytes and in CD3+ T cells in peripheral lymphoid tissues. Western blotting
      yielded a set of bands ranging from 25 kD to 55 kD, resulting from extensive
      alternative splicing. The TCF-1 protein was detectable in all samples of a set of
      22 T-cell malignancies of various stages of maturation, but was absent from a
      large number of other hematologic neoplasms. These observations imply a T cell
      specific function for TCF-1, a notion corroborated by recent observations on Tcf
      1 knock-out mice. In addition, these results indicate that nuclear TCF-1
      expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid
      malignancies.

PMID- 7579400
TI  - Ectopic expression of rhombotin-2 causes selective expansion of CD4-CD8-
      lymphocytes in the thymus and T-cell tumors in transgenic mice.
AB  - Although the proto-oncogene rhombotin-2 (RBTN-2) is widely expressed in most
      tissues, it is not expressed in T cells. We investigated the potential for
      overexpression of RBTN-2 to cause tumors in T cells and other tissues by
      constructing transgenic mice that expressed RBTN-2 under control of the
      metallothionein-1 promoter. Despite overexpression of RBTN-2 in all tissues,
      transgenic mice developed T-cell tumors only, thus indicating that tumorigenesis
      caused by RBTN-2 is T-cell-specific. Thymic tumors were found between 37 and 71
      weeks and were invariably associated with metastasis to nonlymphoid organs.
      Thymuses from apparently healthy transgenic mice were also examined. In some mice
      there was an 10-fold increase in the CD4-CD8- thymocyte subset, yet the total
      number of thymocytes was the same as that in wild-type mice. Thymic homeostasis
      was maintained by a compensatory reduction in the CD4+CD8+ subset. The expansion
      of CD4-CD8- thymocytes was associated with increased expression of RBTN-2 and
      with increased cell proliferation. No differences were found in the proportion of
      thymocytes undergoing apoptosis in transgenic mice. Furthermore, RBTN-2-induced
      expansion of CD4-CD8- cells did not block differentiation of these cells.
      Thymuses with 30% CD4-CD8- cells were essentially monoclonal, indicating that all
      thymic immunophenotypes were derived from a single clone. Overall, our data are
      consistent with the following scenario: (1) RBTN-2 expression in T cells causes
      selective and polyclonal proliferation of CD4-CD8- thymocytes accompanied by a
      compensatory decrease in other thymocyte subsets; (2) a clone with growth
      advantage and differentiation potential is selected and populates the thymus; and
      (3) this clone eventually breaches homeostasis of the thymus, accompanied or
      followed by metastasis to other organs.

PMID- 7579401
TI  - Preferential use of the VH4 Ig gene family by diffuse large-cell lymphoma.
AB  - Ig heavy chain variable region (VH) genes expressed by human diffuse large-cell
      lymphoma (DLC) and follicular lymphoma (FL) were identified and analyzed with
      respect to germline gene families. In 67 cases of FL, VH region genes were
      expressed in a pattern similar to that of normal B cells, with a predominance of
      the large VH3 gene family being used. In contrast, of the 17 cases of DLC, there
      was an extremely biased use of VH genes. Of these DLC tumors, 88% expressed genes
      from the small VH4 gene family; and even among these tumors, there was a limited
      use of genes, with 11 cases producing Igs derived from the VH4.21 germline gene.
      Although most of the VH genes expressed by DLC tumor cells contained mutations
      with respect to their germline counterparts, almost all of these mutations
      occurred before the clonal expansion of the tumor. This contrasts with our
      previous findings of ongoing mutations in FL and represents a fundamental
      difference between these two malignancies. This preferential gene use implies an
      important role for the VH4 gene family, and specifically for VH4.21, in the
      genesis of DLC.

PMID- 7579402
TI  - Autoantibodies to phosphatidylethanolamine (PE) recognize a kininogen-PE complex.
AB  - Demonstration of autoimmune antiphospholipid antibodies (aPA) to negatively
      charged phospholipids (PL) in an enzyme-linked immunosorbent assay (ELISA)
      requires the presence of certain phospholipid-binding plasma proteins, eg, beta 2
      glycoprotein I. We found a requirement for plasma against the electrically
      neutral or zwitterionic phospholipid, phosphatidylethanolamine (PE). Two of these
      PE-binding plasma proteins were identified as high molecular weight kininogen
      (HMWK) and low molecular weight kininogen (LMWK). We studied anti-PE antibody
      (aPE) seropositive plasma from 13 patients with SLE and/or recurrent spontaneous
      abortions by using partially purified kininogens and kininogen binding proteins
      from adult bovine serum isolated by carboxymethyl (CM)-papain affinity
      chromatography. Eleven of 13 sera recognized a kininogen-PE complex and/or a
      kininogen-binding protein-kininogen-PE complex. Some aPE-positive patient sera
      were shown to recognize highly purified HMWK and LMWK by ELISA only when the
      kininogens were presented on a PE substrate. These aPE sera did not recognize PE,
      HMWK, or LMWK when they were presented independently as the sole antigens on the
      ELISA plates. Other aPE-positive sera that did not react with PE-bound HMWK or
      LMWK reacted with the CM-papain column eluate when it was bound to PE, which
      suggests that these aPE recognize factor XI or prekallikrein, which normally bind
      to HMWK. The aPE ELISA reactivity of two patient sera were inhibited by
      preincubation of the CM-papain column eluate in the ELISA plate. These data show
      that most aPE are not specific for PE but require the presence of certain PL
      binding plasma proteins that are kininogens or proteins in complex with
      kininogens. Our studies indicate that aPE bind to different plasma proteins than
      those implicated in anionic PL, aPA ELISA reactivity.

PMID- 7579403
TI  - Immune responses to major histocompatibility complex homozygous lymphoid cells in
      murine F1 hybrid recipients: implications for transfusion-associated graft-versus
      host disease.
AB  - Graft-versus-host disease (GVHD) is currently encountered after bone marrow
      transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in
      apparently immunocompetent recipients has been recently reported with increasing
      frequency. A consistent finding in many of these cases is that the recipient
      received blood from a donor homozygous for one of the recipient's HLA haplotypes.
      However, the observed frequency of TA-GVHD is much lower than the estimated
      probability of this donor/recipient combination. The potential role of recipient
      immune responses in controlling TA-GVHD was investigated using an analogous
      murine model in which GVHD is induced by the injection of parental lymphoid cells
      into unirradiated F1 hybrid recipients. The effect of various immune
      manipulations of the recipient of GVHD induction was assessed by determining the
      number of donor lymphoid cells required to induce GVHD responses. Whereas
      depletion of recipient CD4+ cells increased the number of donor cells needed to
      induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in
      fewer donor cells being needed to induce a GVHD response. These studies suggest a
      central role for functioning recipient CD8 and natural killer cells in the down
      regulation of TA-GVHD development in recipients.

PMID- 7579404
TI  - Clinical significance of surface antigen expression in children with acute
      myeloid leukemia: results of study AML-BFM-87.
AB  - Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and
      cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled
      in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside,
      daunorubicin, etoposide induction and a 6-week seven-drug consolidation
      chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or
      without cranial irradiation and maintenance therapy for 1 year. Five-year event
      free survival for patients with immunophenotypic data was .43 +/- .03 SE. The
      diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the
      recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity
      of 98% (positivity of at least one of these antigens), whereas, with the
      exception of CD41 for French American British (FAB) subtype M7, the expression of
      single cell-surface antigens showed no correlation with morphologic or
      cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined
      by morphologic features and karyotypes could be described by low or high rates of
      surface antigen expression compared with those of other patients. These
      immunophenotypic features most probably associated with specific entities include
      expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer
      rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in
      M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for
      M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or
      CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two
      of the three panmyeloid-associated markers (CD13/33/w65) was common; and
      cytogenetic results frequently showed random abnormalities. Expression of
      lymphoid-, progenitor- and most myeloid-associated antigens had no influence on
      the prognosis, whereas the outcome was significantly better for children with M2
      with Auer rods, M3, or M4Eo or for those with the associated karyotypes
      t(8;21);t(15;17) and inv(16) than for other patients.

PMID- 7579405
TI  - Constitutive overexpression of the L-selectin gene in fresh leukemic cells of
      adult T-cell leukemia that can be transactivated by human T-cell lymphotropic
      virus type 1 Tax.
AB  - L-selectin is an adhesion molecule of the selectin family that mediates the
      initial step of leukocyte adhesion to vascular endothelium. Upon cellular
      activation, expression of the L-selectin gene is downregulated at both the
      protein and mRNA levels. To understand the mechanism of leukemic cell
      infiltration into organs, we studied the expression and regulation of L-selectin
      mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and
      investigated the response of the L-selectin promoter to human T-cell lymphotropic
      virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator. Flow
      cytometry showed that L-selectin was expressed on fresh ATL cells along with
      other activation antigens. Northern blot analysis showed that ATL cells
      overexpressed that L-selectin mRNA and that the level was aberrantly upregulated
      after PMA stimulation. Studies using in situ hybridization showed expression of
      the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL
      patients. Intravenous injection of a rat T-cell line that overexpresses L
      selectin showed increased organ infiltration. The induction of Tax expression in
      JPX9 cells resulted in about a twofold increase in the mRNA expression levels
      compared with the basal level. Chloramphenicol acetyltransferase (CAT) assay
      after transient cotransfection showed about a fivefold transactivation of the L
      selectin promoter by Tax. The serum level of the shed form of L-selectin was
      significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL)
      compared with those of asymptomatic carriers and healthy blood donors (mean +/-
      SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively). These results
      indicated that ATL cells constitutively overexpress the L-selectin gene that can
      be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of
      inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach
      the vascular endothelium, leading to transmigration and organ infitration.

PMID- 7579406
TI  - Detection of major bcr-abl gene expression at a very low level in blood cells of
      some healthy individuals.
AB  - The major bcr-abl fusion gene is presently seen as the hallmark of chronic
      myeloid leukemia (CML) and presumably as the cause of its development.
      Accordingly, long-term disappearance of bcr-abl after intensive therapy is
      considered to be a probable cure of CML. The nested reverse transcriptase
      polymerase chain reaction (RT-PCR) provides a powerful tool for minimal residual
      CML detection. The RT-PCR was optimized by (1) increasing the amount of total RNA
      involved in the reverse transcription reaction to correspond to total RNA
      extracted from 10(8) cells, (2) using a specific abl primer in this reverse
      reaction, and (3) reamplifying 10% of the RT-PCR product in nested amplification.
      This optimized RT-PCR permitted us to detect up to 1 copy of RNA bcr-abl
      synthesised in vitro, mixed with yeast RNA in an equivalent quantity to 10(8)
      white blood cells (WBCs). Using this highly sensitive RT-PCR during the follow-up
      of CML patients, a signal was unexpectedly found in healthy controls. Therefore,
      a systematic study of the possible expression of bcr-abl RNA in the WBCs of
      healthy adults and children and in umbilical cord blood was undertaken. It showed
      the presence of bcr-abl transcript in the blood of 22 of 73 healthy adults and in
      the blood of 1 of 22 children but not in 22 samples of umbilical cord blood.

PMID- 7579408
TI  - Expression of stem cell factor and its receptor by human neuroblastoma cells and
      tumors.
AB  - Bone marrow (BM) is a frequent site of metastasis in children with neuroblastoma
      (NB). Nonhematopoietic cell lines of the same neuroectodermal origin produce both
      stem cell factor (SCF) and its receptor, the product of the c-kit protooncogene
      (c-kit). Because recombinant SCF is likely to be soon clinically tested to
      accelerate BM recovery after high-dose chemotherapy, a treatment administered to
      children with disseminated NB, we addressed the question of whether SCF/c-kit
      complex could play a role in the proliferation and metastasis of NB cells.
      Northern blot analysis showed SCF mRNA transcripts in 7 of 8 (88%) NB cell lines
      and c-kit in 1 (13%). Neither c-kit nor SCF could be detected by Western blotting
      in cell extracts or by surface immunofluorescence and flow cytometry. Soluble SCF
      protein was detected by enzyme immunoassay at low concentrations in the cell
      supernatants in the same 7 NB cell lines. Treatment of 4 NB cell lines by SCF +/-
      cytokines relevant to BM physiology did not induce c-kit antigenic expression or
      modulate 3H-thymidine uptake. Likewise, the latter was not changed by incubating
      the cells with anti-c-kit neutralizing antibodies. Immunohistochemical analysis
      showed weak diffuse or focal staining for SCF and c-kit in few primary or
      metastatic tumor samples, only once simultaneously. We conclude that NB cell
      lines usually produce low levels of soluble SCF but do not express c-kit and that
      both proteins are rarely detected in NB tumors. The SCF/c-kit complex appears to
      be unlikely to stimulate NB growth or metastasis; thus, recombinant SCF could be
      safely administered to children with NB.

PMID- 7579407
TI  - Measurement of whole body interleukin-6 (IL-6) production: prediction of the
      efficacy of anti-IL-6 treatments.
AB  - A major limitation on the therapeutic use of cytokine antagonists is that the
      amount of cytokine to be neutralized in vivo is not presently known. We
      previously reported that anti-interleukin-6 (IL-6) monoclonal antibody (MoAb)
      administered to a patient with multiple myeloma (MM) induced high amounts of IL-6
      to circulate in the form of monomeric immune complexes. Based on this
      observation, the present study developed a new methodology to estimate daily IL-6
      production in 13 patients with MM or renal cancer who received anti-IL-6 MoAb.
      Treatment was considered effective when the production of C-reactive protein
      (CRP) was inhibited. The production of this acute-phase protein by hepatocytes is
      dependent on the activation of IL-6 gp130 transducer. Inhibition of tumor
      proliferation was also evaluated in patients with MM. In 7 of 13 patients whose
      CRP production was completely inhibited (> 96%) and who showed some antitumoral
      effects, whole-body IL-6 production in vivo was less than 18 micrograms/d
      (median, 5.7 micrograms/d; range, 0.5 to 17.5 micrograms/d). In the other 6
      patients, subtotal inhibition of CRP production and a lack of antitumoral
      response were associated with high IL-6 production (median, 180 micrograms/d;
      range, 18 to 358 micrograms/d). These in vivo observations were consistent with
      mathematical modeling that predicted that anti-IL-6 MoAb treatment would be
      efficient only in low IL-6 producers. These data indicate the difficulty of
      neutralizing IL-6 with a single anti-IL-6 MoAb in vivo and call for new
      strategies to avoid accumulation of IL-6 in the form of stable immune complexes.

PMID- 7579410
TI  - Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through
      cell-to-cell contact but downregulate osteocalcin.
AB  - Previous studies have shown that bone marrow, especially the bone
      microenvironment, may play an important role in the pathogenesis of multiple
      myeloma (MM). To elucidate the relationship between myeloma cells and bone cells,
      mainly osteoblasts, we have established a coculture system between two
      interleukin-6 (IL-6)-dependent myeloma cell lines, XG1 and XG6, and the
      osteosarcoma cell lines Saos-2 and MG63. Both osteosarcoma cell lines have
      retained major functions of normal osteoblasts; principally, the capacity to
      produce hematopoietic growth factors (including IL-6) and osteocalcin, a
      noncollagenic protein essential in the bone formation process. Because IL-6 is a
      critical growth factor in MM, we have examined the IL-6 osteoblastic cell
      production in our coculture system. XG1 cells strongly upregulate IL-6 production
      by MG63 and Saos-2 cells. Of major interest, the triggering of IL-6 is totally
      dependent on the physical contact between myeloma cells and osteoblastic cells,
      contact that is partly mediated by CD44, CD56, and fibronectin interactions.
      Osteocalcin production by MG63 and Saos-2 cells has previously been shown to be
      dependent on 1,25-(OH)2D3. We demonstrate that XG1 and XG6 cells reduced the
      amount of osteocalcin in MG63 coculture cell supernatants, a reduction that is
      partly mediated by a soluble factor and by cell-to-cell contact. Notably, whereas
      one of the myeloma cell lines, XG6, has lost its capacity to stimulate IL-6
      production by osteoblastic cell lines, both XG1 and XG6 cell lines remain able to
      reduce the osteocalcin amount, indicating that IL-6 and osteocalcin levels are
      regulated by two different pathways. In conclusion, these data strongly support
      the concept that the bone microenvironment is directly modified by contact with
      myeloma cells and are consistent with the characteristics observed in vivo in
      patients with MM patients, ie, abnormally high IL-6 and low osteocalcin levels,
      respectively.

PMID- 7579409
TI  - Synergy between AUUUA motif disruption and enhancer insertion results in
      autocrine transformation of interleukin-3-dependent hematopoietic cells.
AB  - Previously, we characterized the transposition of an intracisternal type A
      particle (IAP) to the 3' untranslated region (UTR) of the interleukin-3 (IL-3)
      gene, which displaced two of the six AUUUA motifs associated with mRNA stability
      in an IL-3-secreting clone. To determine whether this rearrangement was involved
      in the autocrine transformation of the parental IL-3-dependent FL5.12 cell line,
      the germline (gIL-3) and rearranged IL-3 (rIL-3) genes were isolated and
      subcloned into a gene transfer vector. Moreover, the IAP-long terminal repeat
      (LTR) and the IL-3 3' UTR AUUUA motifs were deleted (rIL-3 + delta LTR and gIL-3
      + delta AUUUA) in some IL-3 constructs to ascertain their role in the
      transformation process. The IAP-LTR was also added to these constructs (rIL-3 +
      delta LTR + IAP-LTR, gIL-3 + delta AUUUA + IAP-LTR, and gIL-3 + IAP-LTR), to
      determine whether it was necessary for autocrine transformation. The ability of
      the modified IL-3 genes to abrogate the IL-3 dependency of FL5.12 cells had the
      following rank order: rIL-3 was greater than rIL-3 + delta LTR + IAP-LTR, which
      was greater than gIL-3 + delta AUUUA + IAP-LTR, which was greater than gIL-3 +
      delta AUUUA, which was equal to rIL-3 + delta LTR, which was greater than gIL-3.
      The half-life of IL-3 mRNA was 20-fold longer in cells containing a mutated as
      opposed to a wild-type AUUUA region. All of the factor-independent cells that
      expressed the IL-3 transgenes secreted IL-3 and were tumorigenic after injection
      into BALB/c nude mice. These results indicated that two events could synergize in
      the autocrine transformation of hematopoietic cells: (1) addition of a
      transcriptional enhancer present in a retroviral LTR, and (2) disruption of an
      mRNA stability region.

PMID- 7579411
TI  - Molecular analysis of cutaneous B- and T-cell lymphomas.
AB  - Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs)
      represent a consistent group of B- and T-cell malignancies. We investigated the
      arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement
      of several oncogenes and the tumor-suppressor gene p53, in a panel of primary
      cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was
      performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6,
      and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and
      NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in
      CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were
      assayed using PCR, single-strand conformation polymorphism analysis, and direct
      DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or
      oncogenes were found in 25 of the 52 CBCLs. In particular, we detected
      rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the
      NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of
      these cases showed a germline arrangement of the Ig genes. Clonal rearrangements
      of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt
      10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53
      gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1)
      clonal rearrangement of Ig genes is frequently undetectable by means of Southern
      blot in CBCLs (60%); (2) genetic lesions are involved in a limited but
      significant fraction of primary CLs showing a molecular marker of clonality
      (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci,
      associated with specific subsets of nodal lymphoid neoplasias, are rarely
      observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may
      play a pathogenetic role in non-acute T-cell malignancies and that, in the
      context of lymphoid malignancies, CLs may represent a favorable target for the
      possible oncogenic potential of the NFKB2/lyt-10 gene.

PMID- 7579412
TI  - The expression pattern of erythrocyte/megakaryocyte-related transcription factors
      GATA-1 and the stem cell leukemia gene correlates with hematopoietic
      differentiation and is associated with outcome of acute myeloid leukemia.
AB  - To understand the clinical implications of transcription factors and their
      biologic roles during cellular differentiation in the hematopoietic system, we
      examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL) gene in
      human leukemia cell lines and various leukemia patients using the reverse
      transcriptase-polymerase chain reaction. Cell lines exhibiting megakaryocytic or
      erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene transcripts, while
      monocytic cell lines had no detectable GATA-1, GATA-2, or SCL gene mRNA. In some
      myeloid cell lines, GATA-1 expression, but not SCL gene expression, was detected;
      GATA-1 expression in HL-60 cells was downregulated during the process of
      monocytic differentiation. We next examined GATA-1, GATA-2, and SCL gene
      expression in 110 leukemia samples obtained from 76 patients with acute myeloid
      leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic
      myeloid leukemia in blast crisis (CML-BC). SCL gene expression was usually
      accompanied by GATA-1 expression and was preferentially detected in patients with
      leukemia exhibiting megakaryocytic or erythrocytic phenotypes, while patients
      with monocytic leukemia were clustered in the group with no detectable GATA-1
      expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL. De
      novo AML patients with SCL gene expression had a lower complete remission (CR)
      rate and had a significantly poorer prognosis. Among the patients with AML not
      expressing SCL, a high percentage of patients with CD7+ AML and CD19+ AML had
      detectable GATA-1, while patients with GATA-1-negative AML had the best CR rate
      (87.5%). Our results suggest that the expression pattern of transcription factors
      reflects the lineage potential of leukemia cells, and GATA-1 and SCL gene
      expression may have prognostic value for the outcome of patients with AML.

PMID- 7579413
TI  - Glucocorticoids inhibit apoptosis of human neutrophils.
AB  - Human neutrophils rapidly undergo apoptotic cell death. Because glucocorticoids
      are known to modulate an array of neutrophil functional activities as well as
      induce rapid apoptosis in susceptible lymphocyte populations, we have examined
      the effects of glucocorticoids on apoptosis in mature human neutrophils. In
      cultures of neutrophils maintained in vitro, the glucocorticoids, dexamethasone,
      6 alpha-methylprednisolone, and hydrocortisone, inhibited the development of
      apoptotic morphology by 59% to 90% when assessed at 12, 24, and 48 hours. In
      contrast, corticosteroids lacking anti-inflammatory activity and progesterone
      failed to affect development of the morphologic features of apoptosis. The
      concentration of dexamethasone required to reduce apoptosis by 50% at 24 hours
      was approximately 5 x 10(-8) mol/L, a concentration that is achievable in plasma
      after dexamethasone treatment. Dexamethasone (10(-6) mol/L), but not
      progesterone, reduced the percentage of hypodiploid (apoptotic) nuclei by 40% to
      90% over this time course. Similarly, dexamethasone reduced the DNA cleavage
      associated with apoptosis and prolonged the viability of neutrophils maintained
      in culture for 12 to 48 hours. Glucocorticoid-mediated modulation of neutrophil
      apoptosis was qualitatively similar, but lesser in magnitude, when compared with
      the effects of granulocyte colony-stimulating factor (100 ng/mL). Thus,
      glucocorticoids exert a protective effect on human neutrophil survival by
      delaying apoptosis.

PMID- 7579414
TI  - Effect of tumor necrosis factor-induced integrin activation on Fc gamma receptor
      II-mediated signal transduction: relevance for activation of neutrophils by anti
      proteinase 3 or anti-myeloperoxidase antibodies.
AB  - Antineutrophil cytoplasmic autoantibodies (ANCA) have been described in sera of
      patients with several forms of systemic vasculitis, including Wegener's
      granulomatosis and microscopic polyarteritis. The two main targets of ANCA in
      vasculitis are proteinase 3 (PR3) and myeloperoxidase (MPO). ANCA are capable of
      activating neutrophils primed by tumor necrosis factor-alpha (TNF-alpha) in
      vitro, which may be relevant for the induction of the vascular inflammation
      observed in vivo. Recently, it has been suggested that engagement of Fc gamma
      receptor IIa (Fc gamma RIIa) on the neutrophils is involved in the activation by
      ANCA. In the present study, we show that activation of the neutrophil respiratory
      burst by anti-PR3 and anti-MPO is strongly enhanced after TNF priming and lost on
      removal of the Fc parts of the antibodies. Similar results were obtained when the
      neutrophils were activated with antibodies against known membrane antigens
      without major changes in the expression of the target antigens. The TNF-induced
      enhancement of the neutrophil activation was not observed when adherence of the
      cells was prevented by continuous stirring of the suspension or by the addition
      of CD18 antibodies before TNF exposure. Hence, our results indicate that
      engagement of both Fc gamma RIIa and beta 2 integrins is instrumental in
      neutrophil activation induced by ANCA.

PMID- 7579415
TI  - Role of the Plasmodium falciparum mature-parasite-infected erythrocyte surface
      antigen (MESA/PfEMP-2) in malarial infection of erythrocytes.
AB  - During intraerythrocytic growth of Plasmodium falciparum, several parasite
      proteins are transported from the parasite to the erythrocyte membrane, where
      they bind to membrane skeletal proteins. Mature-parasite-infected erythrocyte
      surface antigen (MESA) has previously been shown to associate with host
      erythrocyte membrane skeletal protein 4.1. Using a spontaneous mutant of P
      falciparum that has lost the ability to synthesize MESA and 4.1-deficient
      erythrocytes, we examined growth of MESA(+) and MESA(-) parasites in normal and
      4.1-deficient erythrocytes. Viability of MESA(+) parasites was reduced in 4.1
      deficient erythrocytes as compared with that for normal erythrocytes, but MESA(-)
      parasites grew equally well in 4.1-deficient and normal erythrocytes.
      Cytoadherence of MESA(+)- and MESA (-)-parasitized normal and 4.1-deficient
      erythrocytes to C32 melanoma cells was similar, indicating that neither protein
      4.1 nor MESA plays a major role in cytoadherence of infected erythrocytes.
      Localization of MESA in normal and 4.1-deficient erythrocytes was examined by
      confocal microscopy. MESA was diffusely distributed in the cytosol of 4.1
      deficient erythrocytes but was membrane-associated in normal erythrocytes. These
      findings suggest that MESA binding to protein 4.1 plays a major role in
      intraerythrocytic parasite viability.

PMID- 7579416
TI  - Primary structure of murine red blood cell-type pyruvate kinase (PK) and
      molecular characterization of PK deficiency identified in the CBA strain.
AB  - To clarify the molecular abnormality of pyruvate kinase (PK) deficiency
      identified in the mutant mice of CBA-Pk-1slc/Pk-1slc, we cloned murine red blood
      cell-type PK (R-PK) cDNA of those animals. The cDNA sequence spans 1827 bp,
      including an open reading frame that can encode 574 amino acids. Homology in the
      coding sequences between murine and human R-PK was 86.1% at nucleotide and 91.5%
      at amino acid levels. A homozygous missense mutation at nucleotide 1013 GGT-->GAT
      was identified in the cDNA sequence of the mutant, causing a single amino acid
      substitution at no. 338Gly-->Asp of the murine R-PK. Six amino acid residues,
      335Val-336Ala-337Arg-338Gly-339Asp-340L eu, were encoded in exon 8 of both human
      and rat L (liver-type)/R-PK genes and were evolutionarily conserved in PK from
      bacteria through humans. 337Arg was reported to be important for substrate
      binding, suggesting that the amino acid change would impair substrate affinity of
      the PK subunit. A homozygous missense mutation at the catalytic domain has been
      identified in a human PK variant, PK Hong Kong (941ATT-->ACT, 314 Ile-->Thr).
      Although both 1013A and 941C gave rise to an amino acid change adjacent to the
      active site and may interfere with substrate binding to the subunit, the degree
      of anemia was much more severe in the human case. The erythroid-progenitor cell
      number increased in the spleen of Pk-1slc/Pk-1slc mice to a level approximately
      66 times higher than that in normal CBA mice, suggesting that compensatory
      extramedullary erythropoiesis in the spleen of the mutant mice, but not in the
      human variant, might account for the observed difference in the phenotype.

PMID- 7579418
TI  - The flaky skin (fsn) mutation in mice: map location and description of the
      anemia.
AB  - Flaky skin (gene symbol fsn) is an autosomal recessive mutation that causes
      pleiotropic effects of anemia, papulosquamous skin disorder, and gastric
      forestomach hyperplasia. In this report, we assign fsn to distal chromosome 17
      and characterize the anemia. The decrease in hematocrit levels and red blood cell
      counts is significant and persists throughout life in fsn/fsn mice. There is
      compensatory enlargement of the heart, liver, and spleen by 8 weeks of age,
      whereas the thymus is less than one half normal weight. Nucleated cell counts in
      the peripheral blood are increased 15- to 30-fold, primarily due to an increased
      percentage of normoblasts. The fsn/fsn mice examined at 8 weeks of age have
      significantly increased reticulocyte counts and protoporphyrin levels but reduced
      hemoglobin concentration, suggesting possible abnormalities of hemoglobin
      metabolism. Erythrocyte membrane fragility is normal. Compared with normal +/?
      littermates, fsn/fsn mice (1) lack splenic and hepatic stores of elemental iron,
      (2) have the ability to transport 59Fe across the duodenal cells and into the
      blood, (3) have increased levels of transferrin in serum, and (4) have acute loss
      of urinary 59Fe. Hemolysis is indicated by increased serum bilirubin and high
      blood reticulocyte numbers. Collectively, the genetic, hematologic, and
      pathologic data indicate a severe hematologic disorder caused by homozygosity for
      the fsn mutation that differs from other known hematologic mutations in the
      mouse. The mechanism whereby fsn induces the reported pleiotropic effects has yet
      to be elucidated.

PMID- 7579417
TI  - The effect of redox-related species of nitrogen monoxide on transferrin and iron
      uptake and cellular proliferation of erythroleukemia (K562) cells.
AB  - The iron-responsive element-binding protein (IRE-BP) modulates both ferritin mRNA
      translation and transferrin receptor (TfR) mRNA stability by binding to specific
      mRNA sequences called iron-responsive elements (IREs). The regulation of IRE-BP
      in situ could possibly occur either through its Fe-S cluster and/or via free
      cysteine sulphydryl groups such as cysteine 437 (Philpott et al, J Biol Chem
      268:17655, 1993; and Hirling et al, EMBO J 13:453, 1994). Recently, nitrogen
      monoxide (NO) has been shown to have markedly different biologic effects
      depending on its redox state (Lipton et al, Nature 364:626, 1993). Considering
      this fact, it is conceivable that the NO group, as either the nitrosonium ion
      (NO+) or nitric oxide (NO+), may regulate IRE-BP activity by S-nitrosylation of
      key sulphydryl groups or via ligation of NO. to the Fe-S cluster, respectively.
      This hypothesis has been examined using the NO+ generator, sodium nitroprusside
      (SNP); the NO. generator, S-nitroso-N-acetylpenicillamine (SNAP); and the
      NO./peroxynitrite (ONOO-) generator, 3-morpholinosydnonimine hydrochloride (SIN
      1). Treatment of K562 cells for 18 hours with SNP (1 mmol/L) resulted in a
      pronounced decrease in both the RNA-binding activity of IRE-BP and the level of
      TfR mRNA. In addition, Scatchard analysis showed a marked decrease in the number
      of specific Tf-binding sites, from 590,000/cell (control) to 170,000/cell (test),
      and there was also a distinct decrease in Fe uptake. Furthermore, SNP did not
      decrease cellular viability or proliferation. In contrast, the NO. generator,
      SNAP (1 mmol/L), increased RNA-binding activity of IRE-BP, the level of TfR mRNA,
      and the number of TfRs in K562 cells. Moreover, both SNAP (1 mmol/L) and SIN-1
      (0.5 mmol/L) reduced cellular proliferation. The results are discussed in context
      of the possible physiologic role of redox-related species of NO in regulating
      iron metabolism.

PMID- 7579419
TI  - Stimulation of fetal hemoglobin production by short chain fatty acids.
AB  - Butyrate, a four-carbon fatty acid, and its two-carbon metabolic product,
      acetate, are inducers of gamma-globin synthesis. To test whether other short
      chain fatty acids share this property, we first examined whether propionic acid,
      a three-carbon fatty acid that is not catabolized to acetate, induces gamma
      globin expression. Sodium propionate increased the frequency of fetal hemoglobin
      containing erythroblasts and the gamma/gamma + beta mRNA ratios in adult
      erythroid cell cultures and F reticulocyte production in a nonanemic juvenile
      baboon. Short-chain fatty acids containing five (pentanoic), six (hexanoic),
      seven (heptanoic), eight (octanoic), and nine (nonanoic) carbons induced gamma
      globin expression (as measured by increase in gamma-positive erythroblasts and
      gamma/gamma + beta mRNA ratios) in adult erythroid burst-forming unit cultures.
      There was a clear-cut relationship between the concentration of fatty acids in
      culture and the degree of induction of gamma-globin expression. Three-, four-,
      and five-carbon fatty acids were better inducers of gamma globin in culture as
      compared with six- to nine-carbon fatty acids. These results suggest that all
      short-chain fatty acids share the property of gamma-globin gene inducibility. The
      fact that valproic acid, a derivative of pentanoic acid, also induces gamma
      globin expression suggests that short-chain fatty acid derivatives that are
      already approved for human use may possess the property of gamma-globin
      inducibility and may be of therapeutic relevance to the beta-chain
      hemoglobinopathies.

PMID- 7579420
TI  - Allogeneic bone marrow transplantation from HBsAg+ donors: a multicenter study
      from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).
AB  - Hepatitis B virus (HBV)-infected individuals are occasionally used as donors for
      bone marrow transplantation (BMT). We studied the rate of HBV infection and the
      clinical expression of the associated liver disease in patients receiving marrow
      from HBsAg+ donors. We performed a retrospective survey in 14 BMT units in Italy
      in which all BMTs performed between 1984 and 1994 were reviewed and those
      involving HBsAg+ donors were identified. Donors and recipients were analyzed for
      HBV markers and liver disease. A total of 24 of 2,586 patients (0.9%) had
      received an HBsAg+ marrow. HBsAg became detectable in 22% of pre-BMT HBsAg-
      patients, but only 5.5% became chronic HBsAg carriers. Antigenemia developed more
      frequently in anti-HBs- compared with anti-HBs+ patients independently of passive
      prophylaxis with hyperimmune anti-HBs Ig, although the difference was not
      significant. Severe liver failure with death occurred in 21% of patients, which
      was a value greater than that generally observed after BMT in our units (3.7%).
      Patients with an anti-HBe+ donor had higher frequency of liver failure (28% v 0%)
      and alanine aminotransferase peaks as compared with those of patients with an
      HBeAg+ donor. Liver failure was not observed in anti-HBs+ recipients. The use of
      HBsAg+ donors, particularly if anti-HBe+, increases the risk of severe liver
      disease in BMT recipients. Anti-HBs positivity may prevent severe liver damage.

PMID- 7579421
TI  - Analysis of beta-globin mutations shows stable mixed chimerism in patients with
      thalassemia after bone marrow transplantation.
AB  - Beta-thalassemia major (TM) is caused by any of approximately 150 mutations
      within the beta-globin gene. To establish the degree of chimerism after bone
      marrow transplantation (BMT), we have performed molecular analysis of beta-globin
      mutations in 14 patients with TM over a period of 10 years. All patients
      underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using
      either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo
      depletion using CAMPATH 1G in the bone marrow collection bag. To date, at
      different time periods after BMT, seven patients have some degree of chimerism;
      six of these patients, all blood transfusion-independent, have donor cells in the
      range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has
      less than 10% donor cells with, surprisingly, only minimal transfusion
      requirements. The detection of beta-globin gene point mutation, as used here, is
      a highly specific and sensitive marker for engraftment and MC in patients with
      thalassemia. In light of its specificity, the method is applicable in all cases
      of TM, as it is independent of sex and other non-globin-related DNA markers. The
      high incidence of MC found in our patients may be a consequence of the pre-BMT T
      cell depletion. Because MC was associated with transfusion independence, complete
      eradication of residual host cells for effective treatment of TM and possibly
      other genetic diseases may prove not to be essential.

PMID- 7579422
TI  - Unrelated donor marrow transplantation in children.
AB  - Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an
      unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML;
      n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15)
      or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other
      hematologic diseases (n = 16) between June 1985 and April 1993. All patients were
      conditioned with cyclophosphamide and total body irradiation and received a
      combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD)
      prophylaxis. Fourty-six patients received transplants from HLA-identical donors
      and 42 patients received transplants from donors who were minor-mismatched at one
      HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival
      and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first
      or second remission, 10% and 60% for ALL in relapse or third remission, 46% and
      46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29%
      and 69% for other diseases. HLA disparity was not significantly associated with
      lower disease-free survival, but the results suggest more relapses in HLA-matched
      recipients and there was significantly more transplant-related mortality in
      mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections
      associated with acute or chronic GVHD and occurred within the first 2 years after
      transplantation. Granulocyte engraftment occurred in all evaluable patients.
      Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were
      discharged home disease-free at a median of 98 and 103 days, respectively, after
      transplantation (P = not significant [NS]). The incidence of grades II-IV acute
      GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The
      incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched
      recipients (P = NS). One or multiple late adverse events such as cataracts,
      osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease,
      and hypothyroidism have occurred in 11 of 33 (33%) surviving patients.
      Immunosuppression was discontinued in 58% of surviving patients, including all 12
      patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky
      score of 100%. These data show that marrow transplantation from fully or
      partially HLA-matched unrelated donors can be effective therapy for children with
      hematologic disorders and that pretransplantation disease status and
      posttransplantation GVHD remain important factors affecting patient outcome.

PMID- 7579423
TI  - Intensive therapy with peripheral blood progenitor cell transplantation in 60
      patients with poor-prognosis follicular lymphoma.
AB  - Intensive therapy, mainly with purged autologous bone marrow transplantation
      (ABMT), has been proposed in recent years as consolidation treatment in young
      patients with follicular lymphoma. Reported experience with transplantation of
      peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and
      the therapeutic efficacy of intensive therapy followed by unpurged autologous
      PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular
      lymphoma. Twelve patients were in first partial remission (PR), 34 were in second
      partial or complete remission (CR), and 14 were in subsequent progression. At the
      time of the procedure, 39 patients (65%) had persistent bone marrow involvement,
      49 patients (82%) were in PR, and 16 patients had presented with a histologic
      transformation (HT). PBPC were collected after chemotherapy followed by
      granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)
      CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone
      (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen),
      or cyclophosphamide with or without etoposide plus total body irradiation (46
      patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L
      was 13 days. There were five treatment-related deaths, with four being associated
      with a delayed engraftment and all occurring in patients in third or subsequent
      progression. At a median follow-up of 21 months, 48 patients were still alive, 18
      relapsed, and seven died of lymphomas progression. Estimated 2-year overall
      survival (OS) and failure-free survival (FFS) rates were 86% and 53%,
      respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a
      significantly longer rate of OS and FFS than those treated in subsequent
      progression (P = .002 and P = .001, respectively), whereas age, response to
      salvage treatment, presence or absence of residual bone marrow involvement, or
      conditioning regimen had no influence on outcome. Patients with HT tended to have
      a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate
      of engraftment failure, the poor FFS observed in heavily pretreated patients
      suggests that intensive therapy should be performed early in the course of the
      disease. Given the high percentage of patients intensified in PR with residual
      bone marrow involvement, our results are comparable with those achieved with ABMT
      published to date. Prospective trials are warranted to compare this strategy with
      standard therapy in patients with relapsing or PR follicular lymphoma.

PMID- 7579424
TI  - Prestorage leukocyte depletion is not necessarily required for the prevention of
      refractoriness to platelet transfusion.

PMID- 7579426
TI  - Development of a clonality assay for canine hematopoietic stem cells.

PMID- 7579425
TI  - On the differentiative mode of action of All-trans retinoic acid in acute
      promyelocytic leukemia.

PMID- 7579427
TI  - Two common mutations causing factor XI deficiency in Ashkenazi Jews may point to
      a European origin.

PMID- 7579429
TI  - Prolonged administration of low-dose interleukin-2 in human immunodeficiency
      virus-associated malignancy results in selective expansion of innate immune
      effectors without significant clinical toxicity.
AB  - Ten adult patients with human immunodeficiency virus (HIV)-associated
      malignancies (five with lymphoma and five with Kaposi's Sarcoma) were treated
      with a daily subcutaneous injection of interleukin-2 (IL-2) for 90 consecutive
      days in a phase I dose-escalation study. Seven patients had absolute CD4 counts
      below 200/mm3 at the time malignancy was diagnosed. Each lymphoma patient had
      obtained a complete or partial remission with standard chemotherapy before
      initiating IL-2. The daily dose of IL-2 did not change during the 90-day course
      of therapy. Seventeen courses of IL-2 therapy were completed at doses ranging
      from 0.4 x 10(6) U/m2/d to 1.2 x 10(6) U/m2/d without significant (grade III)
      toxicity. Two of two patients experienced grade III toxicity within 21 days of
      initiating IL-2 at a dose of 1.4 x 10(6) U/m2/d, but both patients subsequently
      completed 90 days of therapy at the maximum tolerated dose (MTD) of 1.2 x 10(6)
      U/m2/d. Although there were no significant increases or decreases in T-cell
      subsets at any dose level, there was an increase in absolute natural killer (NK)
      cell number at the three highest doses of IL-2 (mean percent increase 247; 95%
      confidence interval, 124 to 369) that was statistically significant (Wilcoxon one
      sample signed rank test, P = .015). One patient developed an anti-IL-2 antibody
      titer that correlated with minimal NK cell expansion in vitro and in vivo. An
      increase in eosinophils was noted during 9 of 17 courses of IL-2 therapy without
      correlation to IL-2 dose, prior course of IL-2, or NK cell expansion. At the MTD,
      there was no consistent increase in the plasma HIV RNA level over time. Three of
      10 patients had progressive disease while on study. During 50 months of IL-2
      therapy, no patient was treated for an opportunistic infection. We conclude that
      daily low dose subcutaneous IL-2 can be self-administered safely with good
      compliance for prolonged periods of time to patients with HIV-associated
      malignancies, including those with profound immune deficiency. The majority of
      patients show selective expansion of innate immune effectors, ie, NK cells and/or
      eosinophils, in the absence of significant clinical toxicity or increased viral
      burden. These results suggest that low-dose IL-2 therapy should be studied
      further in phase II clinical trials for evidence of activity against malignancy
      and opportunistic infection in this patient population.

PMID- 7579428
TI  - The molecular basis of paroxysmal nocturnal hemoglobinuria.

PMID- 7579431
TI  - Functional differences between two Fc receptor ITAM signaling motifs.
AB  - Most Ig receptors exist as multi-subunit complexes with a unique ligand binding
      alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa
      (CD32) appears unique among FcR because both ligand-binding and signaling
      capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma
      RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs)
      have been defined, in which tyrosines play an important role. Previously, Fc
      gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory
      functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2)
      release and antigen presentation was absent in Fc gamma RIIa, but not in FcR
      gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa
      wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production
      and antigen presentation by B cells. Both of these functions could solely be
      triggered by receptors containing the FcRIIa was capable of functional
      interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL
      2 release and antigen presentation. These data document qualitative differences
      between Fc receptor ITAMs.

PMID- 7579432
TI  - Accelerated reconstitution of platelets and erythrocytes after syngeneic
      transplantation of bone marrow cells derived from thrombopoietin pretreated donor
      mice.
AB  - The recent cloning of the ligand of the c-Mpl hematopoietin receptor has
      indicated a major role for this cytokine in the development of megakaryocytes. In
      this study we have applied c-Mpl ligand (thrombopoietin [TPO]) in the setting of
      syngeneic transplantation in an attempt to accelerate the reconstitution of
      platelets. Donor mice were treated with 20 kilounits (kU)/d TPO intraperitoneally
      (ip) for 5 days. This resulted in a 2.5-fold increment in platelet counts from
      1,119 x 10(9)/L to 2,582 x 10(9)/L (mean, n = 7). Total numbers of hematopoietic
      progenitor cells in bone marrow (BM) and spleen, as assessed in a colony-forming
      unit-granulocyte erythroid monocyte macrophage (CFU-GEMM) colony assay (55.3 v
      38.6 x 10(3) CFU/femur; 27.3 v 16.3 x 10(3) CFU/spleen, mean, n = 7) as well as
      total numbers of burst-forming unit-erythroid (BFU-E) (24.0 v 16.4 x 10(3)/femur;
      10.2 v 1.9 x 10(3)/spleen, mean, n = 7), were significantly higher in TPO-treated
      donors than in saline-treated controls. Female Balb-C mice were lethally (8.5 Gy)
      irradiated and transplanted with 10(5) BM cells. After transplantation, groups of
      mice were treated with recombinant murine TPO at a dose of 20 to 30 kU/d ip or
      subcutaneously (SC) for 5 to 14 days. Using this dose and schedule, TPO did not
      stimulate the recovery of platelets in comparison with control animals
      transplanted with equal cell numbers but given vehicle alone. In other
      experiments, 10(5) BM cells were procured from TPO-treated donor mice and
      transplanted into lethally irradiated recipient mice. In comparison with animals
      transplanted with an equal number of BM cells derived from saline-treated
      controls, recipients of TPO-treated BM cells had significantly faster platelet
      recovery and higher platelet nadir counts (88 v 30 x 10(9)/L, mean, n = 20).
      Transplantation of TPO-treated BM cells also resulted in an accelerated recovery
      of erythrocytes and increased erythrocyte nadir counts (7.2 v 5.0 x 10(12)/L,
      mean, n = 20). At the day of platelet nadir (day 12 after transplantation) these
      animals had higher numbers of BFU-Es (770 v 422, mean, n = 5) in the marrow and
      also had higher reticulocyte counts (44 / 1000 v 8 / 1000 mean, n = 5) in the
      blood. Therefore, the accelerated recovery of erythrocytes may be a direct effect
      of TPO on erythropoiesis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7579430
TI  - A distinct pattern of cytokine gene expression by human CD83+ blood dendritic
      cells.
AB  - Dendritic cells are the most potent antigen-presenting cells of the immune
      system. Although dendritic cells are likely to secrete selective cytokines that
      facilitate antigen presentation, the difficulty in isolating pure dendritic cells
      in sufficient numbers has made assessment of this function imprecise. In this
      study, pure populations of CD83+ human blood dendritic cells were isolated by
      previously established enrichment procedures and subsequent cell sorting.
      Cytokine gene expression was assessed by reverse transcription-polymerase chain
      reaction (RT-PCR) amplification of mRNA. Resting CD83+ dendritic cells expressed
      interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and
      transforming growth factor-beta 1 (TGF-beta 1) mRNA, while activation of cells
      with phorbol myristate acetate induced IL-1 alpha and beta, IL-9, TNF-beta,
      interferon-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), M
      CSF, and G-CSF mRNA expression. Resting CD83+ cells also expressed the Rantes,
      MCP-1, MIP-1 alpha, and MIP-1 beta chemokines, with 1-309 expression induced upon
      activation. Resting and activated CD83+ dendritic cells also expressed receptors
      for IL-2 (CD25), TGF-beta 1 and -beta 3, and GM-CSF as determined by indirect
      immunofluorescence staining. These results indicate that dendritic cells have the
      ability to produce a variety of soluble factors which are likely to contribute
      substantially to the potent allostimulatory activity of these cells.

PMID- 7579433
TI  - Quantitation of the quiescent fraction of long-term culture-initiating cells in
      normal human blood and marrow and the kinetics of their growth factor-stimulated
      entry into S-phase in vitro.
AB  - A method for quantitating the proportion of cycling long-term culture-initiating
      cells (LTC-IC) in heterogeneous populations of human hematopoietic cells is
      described. This procedure involves incubating the cells of interest for 16 to 24
      hours in a serum-free medium containing 100 ng/mL Steel factor (SF), 20 ng/mL
      interleukin-3 (IL-3), and 20 ng/mL granulocyte-colony-stimulating factor (G-CSF),
      with or without 20 microCi/mL of high specific activity 3H-thymidine (3H-Tdr)
      before plating the recovered cells in standard LTC-IC assays. The details of this
      procedure are based in part on the finding that the number of LTC-IC (regardless
      of their cycling status) remains constant for at least 24 hours under these
      culture conditions, as long as 3H-Tdr is not present. In addition, we have
      determined that a 16-hour period of exposure to the 3H-Tdr is sufficient to
      maximize the discrimination of cycling LTC-IC but not long enough to allow a
      detectable redistribution of LTC-IC between noncycling and cycling compartments.
      Finally, any isotope reutilization that may occur is not sufficient to affect the
      LTC-IC 3H-Tdr suicide values measured. Application of this methodology to
      normally circulating LTC-IC showed these to be a primarily quiescent population.
      However, within 72 hours of incubation in a serum-free medium containing SF, IL
      3, and G-CSF, most had entered S-phase, although there was no net change in their
      numbers. This suggests that, under certain conditions in vitro, self-renewal
      divisions of LTC-IC can occur and, at least initially, balance any losses of
      these cells due to their differentiation or death. In contrast, many of the LTC
      IC in freshly aspirated samples of normal marrow were found to be proliferating,
      although those that were initially quiescent could also be recruited into S-phase
      within 72 hours in vitro when incubated under the same conditions used to
      stimulate circulating LTC-IC. This modified 3H-Tdr suicide procedure should
      facilitate further investigation of the mechanisms regulating the turnover of the
      most primitive compartments of human hematopoietic cells and how these may be
      altered in disease states or exploited for a variety of therapeutic applications.

PMID- 7579434
TI  - Homoharringtonine therapy induces responses in patients with chronic myelogenous
      leukemia in late chronic phase.
AB  - Homoharringtonine (HHT) is a plant alkaloid with potent myelosuppressive activity
      and little toxicity when used in a continuous infusion schedule. The antileukemic
      efficacy of HHT has been shown in acute myeloid leukemia, but has not been
      investigated in chronic myelogenous leukemia (CML). Seventy-one patients with
      Philadelphia chromosome-positive (Ph+) CML in late chronic phase (time from
      diagnosis to therapy longer than 12 months) were treated with a continuous
      infusion of HHT at a daily dose of 2.5 mg/m2 for 14 days for remission induction
      and for 7 days every month for maintenance. The median number of courses given
      was 6 (range, 1 to 35) and 21 patients (30%) continue on treatment. Forty-two of
      58 patients (72%) evaluable for hematologic response achieved a complete
      hematologic remission, and 9 (16%) had a partial hematologic remission. Twenty
      two of 71 patients (31%) developed a cytogenetic response; it was major (Ph+
      cells less than 35%) in 11 (15%) and complete (Ph+ cells 0%) in 5 (7%).
      Significant myelosuppression occurred in 39% of induction courses and 9% of
      maintenance courses. Fever or documented infection was present in 26% of
      induction courses and in only 8% of maintenance courses. Nonmyelosuppressive
      toxicity was minimal. Homoharringtonine produced hematologic remissions in the
      majority of patients with advanced chronic-phase CML. Cytogenetic response
      occurred in some patients without an association with myelosuppression, and these
      responses may be prolonged. Future studies investigating homoharringtonine in
      combination with other active agents in CML, such as interferon, are warranted.

PMID- 7579436
TI  - Aggressive treatment for postcardiac transplant lymphoproliferation.
AB  - Posttransplant lymphoproliferative disorder (PTLD) is a frequently fatal
      complication of organ transplantation, occurring in 2% to 6% of cardiac
      recipients. Treatment remains poorly defined. Reduction in immunosuppression is
      effective in a proportion of cases, but mortality on the order of 80% is reported
      for patients requiring chemotherapy. The reason for such poor outcomes is
      unclear, but may be partly caused by the concomitant use of immunosuppressives.
      Nineteen consecutive cardiac recipients with PTLD were studied retrospectively in
      terms of clinical features and outcome. Patients were managed according to a
      uniform treatment approach. Initial therapy was a trial of reduced
      immunosuppression with concomitant acyclovir followed, if unsuccessful, by
      aggressive combination chemotherapy. The regimen used was predominantly ProMACE
      CytaBOM. Six patients with phenotypically polyclonal PTLD presented less than 6
      months after transplantation (median 6 weeks). Only 1 of 4 (25%) treated patients
      responded to reduced immunosuppression; the remainder died of multiorgan failure.
      Thirteen patients presented with phenotypically monoclonal disease > or = 6
      months after transplantation. In 8 of 12 (75%) treated patients initial therapy
      was reduction in immunosuppression. None achieved complete remission (CR) and 2
      experienced fatal rejection. Two patients achieved durable surgical CR. The
      remaining 8 patients received chemotherapy; 2 of 8 (25%) died during treatment, 6
      of 8 (75%) achieved CR. None have relapsed, at a median duration of follow-up of
      38 months. Neutropenic sepsis and subclinical doxorubicin cardiotoxicity at a
      mean cumulative dose of 63 mg/m2 were the principal toxicities. Our data indicate
      that aggressive chemotherapy is both feasible and effective in phenotypically
      monoclonal PTLD refractory to reduced immunosuppression. ProMACE-CytaBOM is well
      suited to cardiac recipients, minimizing doxorubicin exposure and obviating the
      need for concurrent immunosuppressives.

PMID- 7579435
TI  - Activation of the hemostatic mechanism during thrombolysis in patients with
      unstable angina pectoris.
AB  - In patients with myocardial infarction, thrombolytic therapy induces a
      paradoxical activation of the hemostatic mechanism. In patients with unstable
      angina, the effect of thrombolysis on the coagulation cascade is unknown. We
      prospectively measured the plasma concentrations of prothrombin fragment 1 + 2
      and fibrinopeptide A in consecutive patients with unstable angina randomized to
      receive placebo alone (n = 23), streptokinase 1,500,000 IU over 1 hour followed
      by a 48-hour placebo infusion (n = 21), or streptokinase 250,000 over 1 hour
      followed by a continuous infusion of 100,000 IU per hour over 48 hours (n = 20).
      All the patients received intravenous heparin for 72 hours. The plasma levels of
      the different markers were measured at baseline, 90 minutes, 24 hours, and 48
      hours after the start of therapy. The median baseline plasma concentrations of
      prothrombin fragment 1 + 2 and fibrinopeptide A were similar in the three
      treatment groups. In comparison with placebo, an increase in plasma prothrombin
      fragment 1 + 2 and fibrinopeptide A, was observed after 90 minutes in the two
      groups receiving thrombolysis. After 24 and 48 hours, the prothrombin fragment 1
      + 2 levels remained significantly higher only in the patients receiving the 48
      hour streptokinase infusion. In patients with unstable angina, thrombolytic
      therapy induces an activation of the hemostatic mechanism, despite concomitant
      heparin administration; in those receiving a prolonged streptokinase infusion,
      the activation of coagulation persists for as long as the drug is administered.

PMID- 7579437
TI  - Major histocompatibility complex class II-mediated inhibition of hematopoiesis in
      long-term marrow cultures involves apoptosis and is prevented by c-kit ligand.
AB  - Expression of major histocompatibility complex (MHC) class II molecules is
      developmentally regulated and lineage dependent. Their role in hematopoiesis is
      not well defined. Previous studies in a canine model showed that dogs given 920
      cGy of total body irradiation, transplanted with autologous marrow, and treated
      with anti-MHC class II monoclonal antibody (MoAb) immediately posttransplant
      experienced only a transient granulocyte recovery that was followed by graft
      failure. In the present study, the effect of anti-MHC class II MoAbs on canine in
      vitro hematopoiesis was investigated. Anti-MHC class II MoAb H81.9 or B1F6 (both
      recognizing nonpolymorphic determinants) had no inhibitory effect when added
      directly to colony-forming unit-granulocyte-macrophage (CFU-GM) grown in agar.
      However, the addition of intact MoAb or as F(ab')2 fragments to long-term marrow
      cultures (LTMCs) resulted in a dose-dependent inhibition of the generation of CFU
      GM among nonadherent cells. Inhibition was most profound with MoAb added at the
      time of initiation of culture. However, even if MoAb was added 3 weeks after
      recharging LTMCs, CFU-GM generation rapidly decreased. In addition, the number of
      adherent cells in LTMCs decreased; predominantly fibroblast-like cells with
      prominent cytoplasmic vesiculation remained. Acridine orange/ethidium bromide
      staining and TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling
      (TUNEL) tests showed an increase in the proportion of apoptotic cells in both the
      nonadherent and adherent compartments. Binding of anti-MHC class II MoAb to
      unfractionated marrow cells resulted in an increase in free (Ca2+)i; no changes
      in tyrosine phosphorylation pattern were observed. The addition of stem cell
      factor (SCF), but not granulocyte colony-stimulating factor or granulocyte
      macrophage colony-stimulating factor, to LTMCs prevented apoptosis, and the
      generation of CFU-GM was indistinguishable from controls. Similarly, a supportive
      adherent layer was maintained. Thus, anti-MHC class II MoAbs interfere with
      hematopoiesis both in vitro and in vivo. The mechanism involves programmed cell
      death in subpopulations of adherent and nonadherent cells. Inhibition of
      hematopoiesis is abrogated by exogenous SCF.

PMID- 7579438
TI  - Human bone marrow microvascular endothelial cells support long-term proliferation
      and differentiation of myeloid and megakaryocytic progenitors.
AB  - Endothelial cells are a major component of the bone marrow (BM) microenvironment
      that regulate the trafficking and homing of hematopoietic progenitor and stem
      cells. In this paper, we provide evidence that BM endothelial cells (BMECs) also
      support multilineage hematopoiesis by elaboration of soluble cytokines.
      Hematopoietic progenitor cells incubated in direct contact with BMEC monolayers,
      or physically separated by microporous membrane, expanded five-fold to sevenfold
      at 7 days, in the absence of exogenous cytokines. Flow cytometric analysis of
      proliferating progenitor cells grown in the presence of BMEC monolayers showed
      that by day 14 of coculture, 70% to 80% of hematopoietic cells were myeloid,
      expressing CD15 or CD14, and 14% to 19% were megakaryocytic, expressing
      GPIIb/IIIa or GPIb. CD34+ cells derived from umbilical cord blood, cultured in
      the upper chamber of transwell culture plates, as well as the cells grown in
      direct contact with BMEC monolayers, generated progenitors for up to 70 days.
      Unstimulated BMEC monolayers constitutively produce interleukin-6, Kit-ligand,
      granulocyte colony-stimulating factor, and granulocyte macrophage colony
      stimulating factor. These data suggest that BMEC regulate proliferation of
      hematopoietic progenitor cells and long-term culture initiating cells by
      elaboration of lineage-specific cytokines.

PMID- 7579439
TI  - Interleukin-1 alpha upregulates tumor necrosis factor receptors expressed by a
      human bone marrow stromal cell strain: implications for cytokine redundancy and
      synergy.
AB  - To explore the biochemical and physiologic basis of the overlapping effects of
      interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF-alpha) on
      myeloid cytokine production, we have studied the dynamics of granulocyte colony
      stimulating factor (G-CSF) and granulocyte-monocyte colony-stimulating factor (GM
      CSF) production as well as IL-1 receptor and TNF receptor expression in a
      clonally derived bone marrow stromal cell strain (CDCL). IL-1 alpha and TNF alpha
      act in a synergistic manner to stimulate G-CSF and GM-CSF production by CDCL,
      resulting in an increase in CSF secretion that is 250-fold greater than that
      observed with either cytokine alone. This synergism in protein secretion is
      paralleled by synergistic increases the steady-state level of GM- and G-CSF mRNA,
      with supra-additive levels achieved by 24 hours. Coincident with this synergistic
      induction of myeloid CSFs, treatment of CDCL cells with IL-1 alpha induces a 300%
      increase in the expression of TNF receptors. IL-1 alpha induction of TNF
      receptors reaches a peak after 6 hours and gradually returns to baseline level by
      24 hours. IL-1 alpha does not affect TNF receptor ligand binding affinity. A
      kinetic study comparing IL-1/TNF synergistic induction of growth factor secretion
      with IL-1 alpha induction of TNF receptors shows that these events occur in
      parallel. In contrast with the induction of TNF receptors by IL-1 alpha,
      treatment with TNF alpha has no effect on either the number of IL-1 receptors
      expressed by CDCL cells or IL-1 receptor ligand binding affinity. Brief treatment
      of IL-1 alpha/TNF alpha-stimulated CDCL cells with cycloheximide before receptor
      induction reduces the synergistic increase in growth factor mRNA by 40% to 60%
      compared with cells not treated with CHX. Taken together, these results raise the
      possibility that IL-1 alpha cross-induction of TNF receptors may contribute to
      the biochemical mechanisms underlying the synergistic stimulation of G-CSF and GM
      CSF production by IL-1 alpha and TNF alpha.

PMID- 7579440
TI  - Hematopoietic inhibition by interferon-gamma is partially mediated through
      interferon regulatory factor-1.
AB  - Biologic responses to cytokines are mediated by intracellular pathways involving
      induction of signaling and metabolic cascades. Interferon (IFN) regulatory factor
      1 (IRF-1) is a major transcription factor induced not only by IFN-gamma but also
      by other cytokines including tumor necrosis factor-alpha (TNF-alpha). Possible
      IRF-1 binding sequence elements have been located in the promoter regions of
      several genes, including p53, inducible nitric oxide synthase, and cyclin D1. IFN
      gamma and TNF-alpha can inhibit hematopoiesis in vitro and have been implicated
      in the pathophysiology of bone marrow (BM) failure. We investigated whether the
      inhibitory effects of these cytokines were intracellularly mediated through the
      expression of IRF-1 or -2 in target cells. In total BM cells, IRF-1 mRNA
      expression increased after stimulation with IFN-gamma and TNF-alpha; the stronger
      effect was observed with IFN-gamma. In contrast, IRF-2 mRNA expression was
      constitutive and not altered by cytokine stimulation. By gene amplification, low
      levels of IRF-1 mRNA were present in unstimulated, highly purified CD34+ cells;
      on exposure to IFN-gamma and TNF-alpha, amplified IRF-1 mRNA showed a much
      stronger signal than control. When CD34+ cells were treated with IFN-gamma and
      TNF-alpha, IRF-1 antisense oligodeoxynucleotide (ODN) partially reversed the
      suppressive effects on CD34+ cell-derived colony formation by IFN-gamma but not
      those by TNF-alpha. In parallel experiments, IRF-1 antisense ODN decreased both
      IRF-1 protein and mRNA expression. The effects of ODN were sequence-specific and
      concentration-dependent. These results suggest that the inhibitory hematopoietic
      effects of IFN-gamma and TNF-alpha are mediated by different pathways. For IFN
      gamma, IRF-1 is involved in the activation of cellular genes responsible for IFN
      gamma suppressive effects.

PMID- 7579441
TI  - Peripheral blood harvest of unaffected CD34+ CD38- hematopoietic precursors in
      paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone
      marrow progenitor that disrupts glycosylinositol phospholipid (GPI) anchoring of
      cell surface proteins. We recently characterized the expression of GPI-anchored
      decay acclerating factor (DAF) and CD59 during hematopoietic development in PNH
      marrow. We found that, although a subset of early hematopoietic precursors
      identified by the CD34+CD38- phenotype exhibits normal DAF and CD59 expression,
      DAF and CD59 are absent on the majority of CD34+CD38- cells. Pluripotent
      CD34+CD38- hematopoietic stem cells normally circulate in the peripheral blood
      and can be collected by apheresis, cryopreserved, and later used for
      reconstitution of hematopoiesis. In this study, we examined the phenotypes of
      CD34+ cells that are released into the blood of PNH patients. Analyses of
      apheresis samples from three affected individuals showed discrete populations of
      circulating DAF+CD59+CD34+ and DAF-CD59-CD34+ cells. Variable proportions of
      CD34+CD38- cells were present within the peripheral blood CD34+ cells of each
      patient, but in all three cases the DAF+CD59+CD34+CD38- cell subset subset.
      Because CD34+ cells lacking CD38 antigen are highly enriched for self-renewing
      hematopoietic stem cells, these findings indicate that apheresis samples can
      serve as a source of unaffected stem cells for autologous marrow transplantation
      of PNH patients.

PMID- 7579442
TI  - Oligodeoxynucleotides antisense to c-abl specifically inhibit entry into S-phase
      of CD34+ hematopoietic cells and their differentiation to granulocyte-macrophage
      progenitors.
AB  - A number of experimental observations suggest that the proto-oncogene c-abl
      participates in the regulation of hematopoietic cell growth. We used an antisense
      strategy to study the relationship between c-abl expression and hematopoietic
      cell proliferation and differentiation. Purified normal human bone marrow-derived
      CD34+ cells were obtained by immunomagnetic selection and incubated with 18-base
      unmodified antisense oligodeoxynucleotides complementary to the first six codons
      of the two alternative first exons of c-abl, la and lb. At the end of incubation,
      an aliquot of cells was assayed for clonogenic growth and the remainder was used
      for flow cytometric analyses. Cell kinetics were evaluated by means of both
      single parameter DNA and bivariate DNA/bromodeoxyuridine (BrdU) flow cytometry.
      Apoptosis was routinely studied by DNA flow cytometric analysis and, in some
      cases, also through DNA agarose gel electrophoresis for detection of
      oligonucleosomal DNA fragments. Expression of differentiation markers was studied
      by flow cytometry. Exposure to antisense oligonucleotides specifically inhibited
      the accumulation of c-abl mRNA in CD34+ cells. Preincubation with the c-abl
      antisense oligomers reduced the proportion of cells in S-phase from 19% +/- 5%
      (mean +/- SD) to 7% +/- 4% (P < .05), and BrdU labeling from 13% +/- 6% to 6% +/-
      3% (P < .05). Flow cytometry and DNA agarose gel electrophoresis showed that
      treated CD34+ cells accumulated in the G0/G1 region of the DNA histogram with no
      evidence of either differentiation or apoptosis. By contrast, both growth factor
      deprivation and exposure of CD34+ cells to the tyrosine kinase inhibitor
      tyrphostin AG82 clearly induced apoptosis. When cells were preincubated with
      antisense oligonucleotides and then plated for evaluation of colony formation,
      this resulted in a significant inhibition of colony forming unit granulocyte
      macrophage growth (from 44 +/- 15 to 22 +/- 9; P < .01) but had no effect on
      burst-forming unit erythroid growth (24 +/- 11 v 21 +/- 11; P < .05). These
      results suggest that c-abl expression is critical for entry of human CD34+
      hematopoietic cells into S-phase and for their differentiation to granulocyte
      macrophage progenitors. They also indicate that other tyrosine kinases besides
      p145c-alb are active in the prevention of apoptosis, so that inhibition of c-abl
      RNA accumulation arrests CD34+ cells in G0/G1 without activating programmed
      death.

PMID- 7579443
TI  - Terminal differentiation of murine resident peritoneal macrophages is
      characterized by expression of the STK protein tyrosine kinase, a receptor for
      macrophage-stimulating protein.
AB  - STK, a new member of the hepatocyte growth factor receptor family, is the
      receptor for macrophage-stimulating protein (MSP), which acts on murine resident
      peritoneal macrophages. We established polyclonal and monoclonal antibodies
      against STK and characterized the structure of STK protein and STK expression on
      cells of the mononuclear phagocyte system. Western blotting showed that the STK
      transcript is translated into a single-chain precursor and then cleaved into a
      165-kD disulfide-linked heterodimer composed of a 35-kD alpha-chain and a 144-kD
      beta-chain. Western blotting detected STK protein on resident peritoneal
      macrophages, a target of MSP, and showed that it was autophosphorylated in cells
      stimulated by MSP. By flow cytometric analysis using a monoclonal anti-STK
      antibody, we showed that STK protein is expressed on restricted macrophage
      populations such as resident peritoneal macrophages, but not on exudate
      peritoneal macrophages or mononuclear phagocytes of the bone marrow, peripheral
      blood, spleen, or alveoli. Resident peritoneal macrophages were classified into
      two fractions according to their reactivity with an anti-STK antibody and a
      marker antibody for macrophages: STKhigh-F4/80high cells and STKnegative-F4/80low
      cells. Acute exudative macrophages were all STKnegative-F4/80low, but they
      gradually became predominantly STKhigh-F4/80high several days after entrance into
      the peritoneal cavity. These results showed that after monocytes migrate into the
      peritoneal cavity, they undergo terminal differentiation in the peritoneal
      microenvironment. This is the first evidence of tissue-specific terminal
      differentiation of peritoneal macrophages, and this terminal differentiation can
      be characterized by the expression of STK receptor tyrosine kinase.

PMID- 7579445
TI  - Effect of flt3 ligand on the ex vivo expansion of human CD34+ hematopoietic
      progenitor cells.
AB  - A ligand for the tyrosine kinase receptor flt3/flk-2, referred to here as flt3
      ligand (flt3L), was recently cloned. The effect of flt3L on purified human CD34+
      progenitor cells was examined. flt3 receptor (flt3R) was detected on the surface
      of human bone marrow cells that were enriched for CD34 expression. The effects of
      flt3L and the c-kit ligand Steel factor (SLF) on hematopoietic progenitors were
      compared in clonal colony assays. Both factors synergized with Pixy321
      (interleukin-3 [IL-3]-granulocyte-macrophage colony-stimulating factor fusion
      protein) to induce granulocytic-monocytic (GM) and high proliferative potential
      (HPP) colonies and synergized with Pixy321 + erythropoietin (EPO) to induce
      multipotent granulocytic-erythroid-monocytic-megakaryocytic colonies. Although
      SLF had a potent effect on colony formation of erythroid restricted progenitor
      cells (burst-forming unit-erythroid), no effect by flt3L was observed. The
      addition of flt3L to irradiated long-term marrow cultures seeded with CD34+ cells
      augmented both total and progenitor cell production. Ex vivo expansion studies
      with isolated CD34+ bone marrow cells from normal donors showed that flt3L alone
      supported maintenance of both GM and HPP progenitors for 3 to 4 weeks in vitro.
      The addition of flt3L to a growth factor combination of IL-1 alpha + IL-3 + IL-6
      + EPO resulted in a synergistic effect on progenitor cell expansion comparable to
      that observed with the addition of SLF to IL-1 alpha + IL-3 + IL-6 + EPO. These
      data show a function for flt3L in the regulation of both primitive multipotent
      and lineage-committed hematopoietic progenitor cells.

PMID- 7579444
TI  - Inhibition of erythro-myeloid differentiation by constitutive expression of a DNA
      binding-deficient c-myb mutant: implication for c-myb function.
AB  - The c-myb proto-oncogene encodes a nuclear protein involved in the regulation of
      cell proliferation, differentiation, and development. Myb protein contains a DNA
      binding and a transactivating domain thought to mediate its biologic properties.
      The DNA binding domain consists of three repeats (R1, R2, and R3), each
      containing a highly conserved motif of tryptophan residues. A c-myb mutant (DR1
      myb) lacking the last 46 amino acids of R1 and 23 amino terminal residues of R2,
      a region homologous to the ADA-2 yeast transcriptional adaptor, lost DNA binding
      ability, but remained able to transactivate the human heat-shock promoter.
      Transfection of murine 32D and murine erythroleukemia (MEL) cell lines with DR1
      myb caused inhibition of cellular differentiation induced by granulocyte colony
      stimulating factor (G-CSF) and dimethyl sulfoxide (DMSO), respectively. A second
      c-myb mutant (D-ADA2-myb) lacking the first 23 amino acids of R2, also lost DNA
      binding and transactivation activity, but did not inhibit DMSO-induced
      differentiation of MEL transfected cells. These findings suggest that deletion of
      R1 activates a DNA binding-independent mechanism of c-myb function, which may
      involve interaction of Myb with cellular factors.

PMID- 7579446
TI  - Degradation of tissue-type plasminogen activator by human monocyte-derived
      macrophages is mediated by the mannose receptor and by the low-density
      lipoprotein receptor-related protein.
AB  - The balance of tissue-type plasminogen activator (t-PA) production and
      degradation determines its concentration in blood and tissues. Disturbance of
      this balance may result in either increased or decreased proteolysis. In the
      present study, we identified the receptor systems involved in the degradation of
      t-PA by human monocytes/macrophages in culture. Monocytes were cultured and
      became macrophages within 2 days. At 4 degrees C, 125I-t-PA bound to macrophages
      with high (apparent dissociation constant [kd], 1 to 5 nmol/L) and low affinity
      (kd > 350 nmol/L). At 37 degrees C, the cells internalized and degraded t-PA via
      the high affinity binding sites, which were partially inhibited by mannan. The
      low affinity binding sites were 6-aminohexanoic acid-inhibitable and not involved
      in t-PA degradation. Degradation of t-PA was upregulated during differentiation
      of monocytes to macrophages. Dexamethasone further upregulated the mannan
      inhibitable t-PA degradation. Lipopolysaccharide downregulated both mannan
      inhibitable and non-mannan-inhibitable t-PA degradation. Non-mannan-inhibitable
      degradation was completely blocked by recombinant 39-kD receptor-associated
      protein (RAP, inhibitor of lipoprotein receptor-related protein [LRP]), whereas
      mannan-inhibitable degradation was blocked by the addition of a monoclonal
      antibody against the mannose receptor. No differences between the degradation of
      t-PA and functionally inactivated t-PA were observed. We conclude that human
      monocyte-derived macrophages are able to bind, internalize, and degrade t-PA.
      Degradation of t-PA does not require complex formation with plasminogen activator
      inhibitors. The macrophages use two independently regulated receptors, namely,
      the mannose receptor and LRP, for the uptake and degradation of t-PA.

PMID- 7579448
TI  - The Ser 460 to Pro substitution of the protein S alpha (PROS1) gene is a frequent
      mutation associated with free protein S (type IIa) deficiency.
AB  - A Ser 460 to Pro mutation of protein S (PS), involving a T to C transition in
      exon XIII of the protein S alpha (PROS1) gene and known as the Heerlen
      polymorphism, was found in 16 of 85 symptomatic patients with PS deficiency
      (18.8%) and only 1 of 113 healthy subjects (0.8%). Another frequent polymorphism
      was described in exon XV of the PROS1 gene, in the codon for Pro 626 (CCA/CCG).
      We found that Heerlen polymorphism was associated with allele CCA and not with
      allele CCG, suggesting a probable transmission by a common ancestor. Most
      subjects bearing the Ser 460 to Pro mutation were deficient in free PS, but had
      normal total PS levels. Normal levels of the C4b-binding protein (C4b-BP) isoform
      containing a beta chain (C4b-BP beta +) ruled out increased C4b-BP beta + as a
      cause of the free-PS deficiency. The binding curves of the mutated (Heerlen) PS
      on C4b-BP immobilized on microplates were biphasic, suggesting that one molecule
      of C4b-BP can bind two molecules of Heerlen PS. Because normal PS binds to C4b-BP
      with 1:1 stoichiometry, this may explain the free-PS deficiency observed in
      patients carrying the Ser 460 to Pro mutation.

PMID- 7579447
TI  - Thrombin modulates synthesis of plasminogen activator inhibitor type 2 by human
      peripheral blood monocytes.
AB  - Fibrin deposition is characteristic of inflammatory diseases. The monocytes is
      central to the inflammatory response and can affect fibrinolysis by expression of
      urokinase (u-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI
      2, respectively). This study examines whether thrombin, which promotes fibrin
      deposition, can contribute to fibrin persistence by modulating expression of
      proteins of the fibrinolytic system. Monocytes were isolated from human
      peripheral blood and analyzed for PAI-2, PAI-1, and u-PA antigens by enzyme
      linked immunosorbent assay (ELISA). Monocytes responded to thrombin by increased
      expression of PAI-2 in a dose- and time-dependent manner, with maximal synthesis
      at a concentration of 1 U/mL to 10 U/mL. This trend was also evident for PAI-1,
      which was present at much lower levels. Thrombin and lipopolysaccharide (LPS)
      stimulated comparable levels of PAI-2, studied at the antigen and mRNA level. The
      dose effet of LPS on PAI-2 and PAI-1 was found to differ from that of thrombin.
      The level of u-PA was undetectable by ELISA and zymography in all samples.
      Thrombin stimulates PAI-2 synthesis by human monocytes, therefore creating an
      imbalance in the fibrinolytic system. This may contribute to persistence of
      fibrin, deposited during inflammation.

PMID- 7579450
TI  - Platelet adhesion to fibronectin in flow: the importance of von Willebrand factor
      and glycoprotein Ib.
AB  - We describe glycoprotein (GP) Ib as a mediator of adhesion to fibronectin,
      specifically in flow. A monoclonal antibody (MoAb) directed to the von Willebrand
      factor (vWF)-binding site on this receptor or the absence of this receptor on the
      platelet membrane, in the case of a patient with the Bernard-Soulier syndrome,
      reduced platelet coverage to fibronectin to approximately 30% of the control
      value. A MoAb directed to the GP Ib-binding site on vWF showed a similar effect.
      With washed platelets in the absence of plasma vWF, the inhibitory effect of the
      anti-GP Ib antibody was the same as with whole blood. No inhibition with the anti
      GP Ib antibody was observed when we used blood from patients with severe von
      Willebrand disease (vWD) or from a patient with vWD type I (platelet low).
      Addition of vWF to vWD blood resulted in restoration of adhesion. Immunoelectron
      microscopy on platelets adhering to fibronectin showed that GP Ib was
      homogeneously distributed over the entire surface of the platelet. vWF was
      present at the central zone and the edges of the platelet and at the basal
      interface between the platelet and the fibronectin surface. No direct binding of
      vWF to fibronectin could be demonstrated. These data indicate that GP Ib-mediated
      adhesion to fibronectin fully depends on vWF and that normal levels of plasma or
      platelet vWF are sufficient for optimal adhesion to fibronectin. The data suggest
      that the presence of platelets during perfusion is a prerequisite for vWF to
      support platelet adhesion to fibronectin.

PMID- 7579451
TI  - Intracellular events determine the fate of antithrombin Utah.
AB  - We sought to determine whether intracellular or extracellular events contribute
      to the decrease in circulating antithrombin (AT) levels that is seen in subjects
      with the Utah mutation (Pro 407 to Leu). Site-directed mutagenesis was used to
      recreate this mutation within a previously characterized rabbit AT cDNA. Cell
      free expression of the mutated cDNA yielded an AT protein that failed to react
      with thrombin. Expression of the rabbit AT-Utah protein in transiently
      transfected Cos cells resulted in a 10-fold decrease in the amount of AT antigen
      detected in the conditioned media, as compared with that seen with the wild-type
      recombinant AT. This effect was not caused by variations in transfection
      efficiency, because AT levels were normalized to the product of a cotransfected
      plasmid, chloramphenicol acetyl transferase. Moreover, on Northern blot analysis,
      AT mRNA levels were comparable in cells expressing either the rabbit AT-Utah or
      wild-type recombinant rabbit AT. Immunoblots of conditioned media from the two
      populations of transfected cells showed that the recombinant AT-Utah protein was
      intact. The results obtained with Cos cells were reproduced using permanently
      transfected Chinese hamster ovary (CHO) cells. Pulse-chase experiments with the
      CHO lines showed that both initial levels of rabbit AT-Utah after the pulse
      labeling and the rate of subsequent secretion during the chase period were
      reduced compared with that seen with cells expressing the wild-type AT. The
      observed reduction in AT secretion was also observed for the AT-Oslo mutation
      (Ala 404 to Thr) when recreated in the rabbit AT background, and expressed in Cos
      cells. In these experiments, the media levels of mutant AT were reduced by 50%,
      compared with wild-type. These results show that intracellular events, as opposed
      to accelerated clearance or other extracellular causes, contribute to the paucity
      of AT secretion seen in these strand 1C AT mutants.

PMID- 7579449
TI  - Protein S deficiency type I: identification of point mutations in 9 of 10
      families.
AB  - We identified potentially causative mutations in the active protein S gene (PROS
      1) by direct sequencing of PROS 1-specific polymerase chain reaction (PRC)
      products of all 15 exons, including exon-intron boundaries in 10 families with
      hereditary protein S deficiency type I. Seven different mutations were found in 9
      of 10 families, including one frame shift mutation, a previously published splice
      site mutation (both occurring in two unrelated families), four missense
      mutations, and a stop codon at the beginning of exon 12. In family studies,
      cosegregation of the mutation with the disease could be demonstrated for five
      mutations; for two missense mutations, this was not possible due to limited
      family data. All seven mutations were the only abnormalities identified in the
      respective index patients and were absent in 44 to 62 normal individuals.
      Therefore, they most likely represent the causal gene defects. For five
      mutations, analysis of ectopic RNA could be performed. Mutant transcripts were
      present in the case of the frame shift and three of the missense mutations, while
      no mutant RNA could be detected in the case of the stop codon.

PMID- 7579452
TI  - Retention of glycoprotein Ib/IX receptors on external surfaces of thrombin
      activated platelets in suspension.
AB  - The present study has evaluated the hypothesis stating that glycoprotein (GP)
      Ib/IX, the receptor for von Willebrand factor (vWF), is downregulated and cleared
      from exposed surfaces to channels of the open canalicular system (OCS) on
      platelets activated by thrombin in suspension. Cryosections of resting and
      thrombin-activated platelets fixed at intervals of 1 to 30 minutes after
      stimulation by thrombin and stained with antiglycocalicin antibody and protein A
      gold showed no decrease in the density of GPIb/IX receptors on the platelet
      surface or increase on linings of the OCS at any interval after stimulation by
      thrombin. Thin sections of platelets exposed to thrombin in suspension followed
      by settling onto a plastic chamber for intervals of 1 to 30 minutes revealed
      retention of GPIb/IX receptors on exposed surfaces detected by vWF, anti-vWF, and
      protein A gold throughout the 30-minute period of study. Results of this
      investigation indicate that GPIb/IX receptors remain on the surface of platelets
      activated by thrombin in suspension, are not cleared to the OCS, and retain the
      ability to bind vWF for at least 30 minutes.

PMID- 7579453
TI  - Critical role of CD28/B7 costimulation in the development of human Th2 cytokine
      producing cells.
AB  - CD28 is a major costimulatory signal receptor for T cells. We have used human
      naive CD4+ cells from cord blood to analyze the effect of the CD28/B7
      costimulatory pathway on development of T helper (Th) subsets. We show that CD28
      costimulation is critical for development of the Th2 cytokine-producing cells and
      that in the absence of CD28 costimulation, cells are not primed to produce Th2
      cytokines and consequently "default" to the Th1 subset, independent of the
      presence of exogenous cytokines. After CD28 costimulation, cells differentiate
      into a subset that produces Th2 cytokines. However, further CD28 costimulation is
      not required to maintain Th2 cytokine production. We conclude that D28
      costimulation is critical for the development of Th0 and Th2 subsets, but not for
      the maintenance of cytokine production.

PMID- 7579454
TI  - Rolling in P-selectin-deficient mice is reduced but not eliminated in the dorsal
      skin.
AB  - P-selectin-mediated rolling is believed to be important in the recruitment of
      leukocytes to tissue after ischemia-reperfusion injury. The dorsal skin chamber
      was used to examine differences in the rolling and stable adhesion of circulating
      leukocytes in subcutaneous (SC) vessels of P-selectin-deficient and age-matched
      wild-type mice, both under basal conditions and after ischemia-reperfusion.
      Rolling in the postcapillary venules in SC tissue of P-selectin-deficient mice
      was significantly lower than that in wild-type mice under the basal conditions
      and post-ischemia-reperfusion (P < .05), but was not eliminated by the deletion
      of the P-selectin gene. No significant difference between P-selectin-deficient
      and wild-type mice in shear rate or leukocyte-endothelial adhesion was observed
      up to 24 hours after ischemia-reperfusion. These results show that P-selectin
      mediated rolling is not a prerequisite for ischemia-reperfusion-induced leukocyte
      endothelial adhesion in the skin.

PMID- 7579455
TI  - Two pathways of exocytosis of cytoplasmic granule contents and target cell
      killing by cytokine-induced CD3+ CD56+ killer cells.
AB  - Cytokine-induced killer (CIK) cells are non-major histocompatibility complex
      restricted cytotoxic cells generated by incubation of peripheral blood
      lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1,
      and interferon-gamma. Cells with the greatest effector function in CIK cultures
      coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by
      MoAbs directed against the cell surface protein leukocyte function associated
      antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic
      cytotoxic granule contents to the extracellular space upon stimulation with anti
      CD3 MoAbs or susceptible target cells. Maximal granule release was observed from
      the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are
      lytic to target cells. Treatment of the effector cells with a cell-permeable
      analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and
      target cell-induced degranulation and cytotoxicity of CIK cells. The
      immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3-mediated
      degranulation, but did not affect cytotoxicity of CIK cells against tumor target
      cells. In addition, degranulation induced by target cells was unaffected by CsA
      and FK506. Our results indicate that two mechanisms of cytoplasmic granule
      release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity
      proceeds through a cAMP-sensitive, CsA- and FK506-insensitive pathway triggered
      by yet-to-be-identified target cell surface molecules.

PMID- 7579457
TI  - Differential activation of leukotriene biosynthesis by granulocyte-macrophage
      colony-stimulating factor and interleukin-5 in an eosinophilic substrain of HL-60
      cells.
AB  - Cytokines can stimulate eosinophils to produce cysteinyl leukotrienes (LTs) in
      the lung that provoke tissue destruction associated with asthma. Priming of an
      eosinophilic substrain of HL-60 cells (HL-60#7) with recombinant human
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF) before ionophore
      challenge was found to produce an apparent 45% increase in total LT production in
      a dose-dependent manner (ED50 = 150 pmol/L) that could be accounted for by a
      decrease in the time required for maximal formation of LTs. GM-CSF had no effect
      on the kinetic parameters of LTC4 synthase and therefore probably acts upstream
      of this catalytic event. Incubation with interleukin-5 (IL-5), however, had no
      effect on LT biosynthesis. This differential priming ability was not a
      consequence of different receptor populations or differences in the affinity or
      stability of the ligand-receptor complexes of GM-CSF and IL-5. GM-CSF and IL-5
      each displayed similar populations of high-affinity binding sites and neither GM
      CSF nor IL-5 were able to cross-compete for the other's receptor binding sites.
      Analysis of phosphotyrosine patterns suggest that IL-5 is incapable of
      transducing a signal in eosinophilic HL-60#7 cells even though IL-5 and GM-CSF
      receptors mediate signal transduction via a common beta-chain component that is
      also necessary for high-affinity binding. Overall, this unique system may permit
      the dissection of distinct events responsible for specific intracellular signals
      transduced separately by GM-CSF or IL-5.

PMID- 7579456
TI  - Granzyme B and perforin lytic proteins are expressed in CD34+ peripheral blood
      progenitor cells mobilized by chemotherapy and granulocyte colony-stimulating
      factor.
AB  - Granzyme B and perforin are cytoplasmic granule-associated proteins used by
      cytotoxic T lymphocytes and natural killer (NK) cells to kill their targets.
      However, granzyme B gene expression has also been detected in a non-cytotoxic
      hematopoietic murine multipotent stem cell line, FDCP-Mix. The objective of the
      present study was to investigate whether granzyme B and perforin could be
      expressed in human hematopoietic CD34+ cells and if present, discover what their
      physiologic relevance could be. The primitive CD34+ human cell line KG1a was
      investigated first and was found to express granzyme B and perforin. Highly
      purified hematopoietic stem/progenitor cells were then selected using the CD34
      surface antigen as marker. Steady-state bone marrow (BM) CD34+ cells did not
      contain these proteins. Peripheral blood (PB) CD34+ cells, which had been induced
      to circulate, were also analyzed. After chemotherapy (CT) and granulocyte colony
      stimulating factor (G-CSF) treatment, CD34+ cells strongly expressed mRNAs and
      proteins of granzyme B and perforin. In contrast, CD34+ cells mobilized by G-CSF
      alone were negative. Western blot analysis further showed that granzyme B and
      perforin proteins were identical in CD34+ cells and activated PBLs. Such proteins
      might be implicated in the highly efficient migration of CD34+ stem/progenitor
      cells from BM to PB after CT and G-CSF treatment. The cellular adhesion
      mechanisms involved in the BM homing of CD34+ cells are disrupted at least
      temporarily after CT. The Asp-ase proteolytic activity of granzyme B on
      extracellular matrix proteins could be used by progenitor cells for their rapid
      detachment from BM stromal cells and perforin might facilitate their migration
      across the endothelial cell barrier.

PMID- 7579458
TI  - Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma,
      Hodgkin's disease, and reactive lymphoid lesions.
AB  - Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some
      pathologic and immunohistochemical similarities, and a histogenetic relationship
      between them has been suggested by some investigators. By cytogenetic study, the
      t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of
      the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel
      tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the
      nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of
      npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid
      lesions since there is contradictory information in the literature on the
      occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in
      8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with
      reactive lesions contained amplifiable template. All positive ALCL had the T or
      indeterminate phenotype and occurred in young adults or children. There was very
      good correlation between a cytogenetically detectable t(2;5) and a positive
      signal by RT-PCR. Our results indicate a selective but relatively infrequent
      association between the t(2;5) and ALCL of T or indeterminate phenotype, not
      shared with HD or reactive hyperplasia.

PMID- 7579459
TI  - Increased glucose metabolism in untreated non-Hodgkin's lymphoma: a study with
      positron emission tomography and fluorine-18-fluorodeoxyglucose.
AB  - Glucose metabolism has been shown to be increased in neoplastic tissue. It has
      been suggested that high activity of glucose metabolism is associated with a high
      grade of malignancy of human cancer. We studied in vivo glucose metabolism in 22
      patients with untreated non-Hodgkin's lymphoma with fluorine-18
      fluorodeoxyglucose (FDG) and positron emission tomography (PET). FDG uptake in
      lymphoma deposits was measured blinded to clinical data, and compared with
      histologic classification and proliferative activity. Tracer uptake was measured
      by using two indices of FDG accumulation: the standardized uptake value (SUV) and
      the regional metabolic rate (rMR) for the tracer. The median SUV of the lymphomas
      was 8.5 (range, 3.5 to 31.0), and the median rMR 22.7 mumol/100 g/min (range, 9.0
      to 124.3 mumol/100 g/min). A high FDG uptake in tumors was associated with high
      histologic degree of malignancy as defined by the Working Formulation (P = .005
      for the SUV, and P = .04 for the rMR) or by the Kiel classification (P = .003 for
      the SUV, and P = .02 for the rMR). A high FDG accumulation was also associated
      with a high S-phase fraction (r = .786 for the SUV, P = .0002; and r = .774 for
      the rMR, P = .02). We conclude that in untreated non-Hodgkin's lymphomas high FDG
      uptake is associated with high histologic grade of malignancy and a high
      proliferation rate. This minimally invasive method may find application in
      assessing lymphoma lesions in patients who are poor candidates for surgery, and
      it may provide further information in cases where the grade of aggressiveness of
      lymphoma is not settled based on clinical or histologic data.

PMID- 7579460
TI  - Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell
      lymphoma.
AB  - The origin of low-grade mucosa-associated lymphoid tissue (MALT)-type B-cell
      lymphoma is still unclear. Using a novel two-step procedure, we have sequenced
      the Ig VH genes expressed by cells from four patients with gastric low-grade MALT
      type lymphoma. The nucleotide sequences of the complementarity determining region
      3 (CDR3) of the genomic DNA were first amplified using consensus oligonucleotide
      primers, then sequenced. Based on the CDR3 sequence amplified from each MALT
      lymphoma, individual tumor-specific primers were synthesized and used directly in
      the polymerase chain reaction (PCR) to analyze the sequences of their Ig heavy
      chain variable region. When compared with the germ-line sequence, many nucleotide
      substitutions, mainly in the CDRs, were found in the variable gene sequences of
      the four MALT lymphomas. The mutations showed a high replacement-to-silent ratio
      and were distributed in a way which suggested that the tumor cells had been
      positively selected through their antigen receptor. Our findings indicate that
      the MALT-type lymphoma B cells are hypermutated postgerminal center lymphocytes
      that have undergone antigen selection.

PMID- 7579461
TI  - Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of
      cultured blast cells from patients with acute promyelocytic leukemia.
AB  - The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its
      reversal by administration of all-trans retinoic acid (ATRA) have been
      investigated. Bone marrow promyelocytic blasts from nine patients with APL were
      cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9)
      were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and
      then assayed for procoagulant activity (PCA), elastase activity, tissue factor
      (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase-type
      plasminogen activator (u-PA) antigen. PCA was determined by a recalcification
      assay. Elastase was measured by an amidolytic assay (S-2484). TF, t-PA, and u-PA
      antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant
      promyelocytes isolated from the patients had increased levels of PCA and TF as
      compared with the control polymorphonucleates, and low levels of elastase, t-PA,
      and u-PA; the patient blast PCA level was significantly related to the degree of
      hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and
      was significantly correlated to the TF antigen values. In the cultures without
      ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels
      remained essentially unchanged. In the presence of ATRA, all parameters (except u
      PA) decreased during the culture time. Thus, a major role of the promyelocytic
      blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the
      ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.

PMID- 7579462
TI  - Different genetic pathways in leukemogenesis for patients presenting with therapy
      related myelodysplasia and therapy-related acute myeloid leukemia.
AB  - Development of myelodysplasia (MDS) with subsequent progression to acute myeloid
      leukemia (AML) is an example of the multistep process of malignant transformation
      in which each step often relates to genetic abnormalities that can be directly
      seen as chromosomal aberrations. Therapy-related MDS and AML (t-MDS and t-AML)
      may serve as an ideal model for a study of the genetic evolution of MDS and AML
      because chromosomal abnormalities are observed in most cases and because the
      disease is often diagnosed early due to a close patient follow-up. The
      cytogenetic characteristics at diagnosis were studied in 137 consecutive cases of
      t-MDS and t-AML, including 22 new cases, and correlated with the clinical
      characteristics and the course of the disease. Balanced translocations to
      chromosome bands 11q23 and 21q22 represent primary steps in pathways leading
      directly to overt t-AML. Specific chromosomal deletions or losses, on the other
      hand, represent primary or secondary events in alternative pathways leading to t
      MDS with potential for subsequent transformation to overt t-AML. Loss of a whole
      chromosome 7 (-7) or deletion of its long arm (7q-) and deletion of the long arm
      of a chromosome 5 (5q-) were the most frequent primary abnormalities
      significantly related to t-MDS. Loss of a whole chromosome 5 (-5) was also a
      primary event, but surprisingly, was observed equally in t-MDS and in t-AML.
      Deletion of chromosome 13, including bands q13q14, was another less common
      primary aberration of t-MDS. Except for -7 and del(13q), these primary
      aberrations were most often observed together with secondary abnormalities. These
      included balanced aberrations involving band 3q26 and various deletions of
      chromosome 3, a gain of a whole chromosome 8, deletions of the short arm or loss
      of chromosomes 12 and 17, loss of a whole chromosome 18, and deletions of the
      short arm of chromosome 21. Deletions or loss or chromosomes 5 and 7 were
      significantly associated with previous therapy with alkylating agents (P = .002),
      and balanced translocations to chromosome bands 3q26, 11q23, and 21q22 were
      significantly associated with previous therapy with drugs targeting DNA
      topoisomerase II (P < .00005). Other characteristic aberrations were not related
      to any specific type of therapy. The molecular changes believed to contribute to
      the development of t-MDS and t-AML have been identified for many of these
      chromosomal abnormalities.

PMID- 7579464
TI  - Histamine distribution in human basophil secretory granules undergoing FMLP
      stimulated secretion and recovery.
AB  - We examined subcellular histamine localizations in purified human basophils that
      were stimulated to degranulate with FMLP using an ultrastructural enzyme-affinity
      technique. Basophils were collected at early (0, 20 seconds, 1 minute) and late
      (10 minutes to 6 hours) time points poststimulation and were prepared for routine
      ultrastructural and diamine oxidase-gold (DAO-gold) cytochemical analysis.
      Histamine was present in unaltered cytoplasmic secretory granules (30.77 gold
      particles per square micrometer; P < .001 compared with background); specificity
      controls (histamine absorption, diamine oxidase digestion) abrogated granule
      labeling for histamine. Altered granules in stimulated cells were not
      significantly labeled for histamine, as compared with background (P = not
      significant); unaltered granules in the same cells contained more histamine than
      altered granules (P < .05). During recovery times, spanning 10 minutes to 6
      hours, granules again appeared to be electron-dense and contained histamine
      (33.49/microns2; P = not significant as compared with unaltered granules in 1
      minute FMLP-stimulated cells, and P < .05 as compared with altered granules in 1
      minute FMLP-stimulated samples). Other structures devoid of histamine in actively
      secreting cells included extruded granules and intragranular and extruded Charcot
      Leyden crystals. Recovering basophils displayed morphologic evidence of material
      and membrane conservation, granule content condensation, and biosynthesis.
      Subcellular histamine-rich sites in actively recovering basophils included
      condensing granules and collections of cytoplasmic vesicles in three locations:
      beneath the plasma membrane, adjacent to granules, and in the Golgi region. These
      studies show that unaltered granules of actively releasing human basophils, as
      well as similar granules that are reconstituted after FMLP-stimulated
      degranulation, contain histamine, but that altered granules in stimulated cells
      undergoing degranulation are devoid of histamine. Reconstitution of histamine
      rich granules is associated with DAO-gold-positive cytoplasmic vesicles,
      suggesting transport of histamine derived from either new synthesis, re-uptake of
      released histamine, or both, to reconstituted granules.

PMID- 7579463
TI  - Heterogeneity of neutrophil antibodies in patients with primary Sjogren's
      syndrome.
AB  - Our aims were to determine the prevalence of neutrophil antibodies in patients
      with primary Sjogren's syndrome (pSS), identify their target antigen(s), and
      evaluate their functional significance. Neutrophil antibodies were detected using
      an indirect immunofluorescence (IIIF) test and an enzyme-linked immunosorbent
      assay (ELISA), using recombinant human Fc-gamma receptor (Fc gamma RIIIb) as a
      capture agent. Luminol-dependent chemiluminescence was then measured by an
      established technique. Antibodies to neutrophils were detected in 30 of 66
      patients (45%) and categorized on the basis of positivity for the two assays:
      IIF+/ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and
      IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies
      directed to the neutrophil specific Fc gamma RIIIb, and none of them bound to
      NAnull neutrophils. The titer of neutrophil-reactive antibodies (groups A and B)
      showed no correlation with the neutrophil count, but these autoantibodies did
      reduce the cell ability to generate a respiratory burst. Thus, neutrophil
      antibodies are common in patients with pSS. Their main target appears to be Fc
      gamma RIII, and this may partly account for the dysfunction in Fc gamma R
      mediated clearance by the reticuloendothelial system reported in these patients.

PMID- 7579467
TI  - Decreased content of protein 4.2 in ankyrin-deficient normoblastosis (nb/nb)
      mouse red blood cells: evidence for ankyrin enhancement of protein 4.2 membrane
      binding.
AB  - Homozygous normoblastosis (nb/nb) mice, whose red blood cell (RBC) membranes are
      nearly completely deficient in full-length 210-kD ankyrin, were used to study
      interactions between ankyrin and protein 4.2 (P4.2). Although it is unclear
      whether or not these proteins interact in the membrane, both ankyrin and P4.2
      bind to the cytoplasmic domain of band 3 (cdb3). In addition to the complete
      deficiency of full-length ankyrin, nb/nb RBC membranes are also partially
      spectrin deficient, resulting in morphologically spherocytic and mechanically
      fragile cells. A new finding was that nb/nb RBC membranes are severely
      (approximately 73%) P4.2 deficient compared with wild type (+/+) or high
      reticulocyte mouse RBC membranes. Metabolic labeling of nb/nb reticulocytes
      showed active P4.2 synthesis at levels comparable with high reticulocyte controls
      suggesting that the nb/nb P4.2 deficiency was not the result of defective P4.2
      synthesis. Reconstitution of nb/nb inside-out vesicles (IOVs) with human RBC
      ankyrin restored ankyrin levels to approximately 80% of +/+ IOV levels and
      increased binding of exogenously added human RBC P4.2 by approximately 60%. These
      results suggest that ankyrin is required for normal associations of P4.2 with the
      RBC membrane.

PMID- 7579466
TI  - Molecular analysis in three cases of X91- variant chronic granulomatous disease.
AB  - Defects in gp91-phox, the large subunit of cytochrome b558 (b-245) give rise to X
      linked chronic granulomatous disease (CGD), a rare inherited condition
      characterized by an extreme susceptibility to bacterial and fungal infection. In
      the majority of cases, the phagocytes are unable to generate any superoxide owing
      to complete absence of the flavocytochrome. However, a small minority of these
      patients do have some phagocytic oxidase activity. We describe here an analysis
      of the molecular basis of the disease in three such variant patients with lesions
      in the gene coding for gp91-phox on the X chromosome. Three different genetic
      lesions were found, resulting in the substitution of tyrosine for cysteine 244, a
      deletion of one of three lysines 313 through 315, and the deletion of the six C
      terminal amino acids, respectively. The functional consequences of these defects
      on oxidase activity was a reduction to 12%, 3.6%, and 2.1% of the normal levels,
      respectively. Corresponding levels of gp91-phox were 20%, 8%, and 16% of normal
      classifying these patients as X91-. Microbicidal assays showed that killing of
      Staphylococcus aureus was grossly impaired in cells in which there was 12% normal
      activity. This implies that if gene therapy is to be applied, it must restore
      oxidase activity to a much higher level than that present in the cells of this
      patient. The sites of two of the mutations were analyzed on a model of the C
      terminal half of the gp91-phox, based on the crystal structure of the homologous
      protein ferrodoxin NADP reductase. Possible structural consequences of the
      mutations were examined.

PMID- 7579465
TI  - Activation of Lyn is a common element of the stimulation of human neutrophils by
      soluble and particulate agonists.
AB  - The functional responsiveness of human neutrophils is known to be initiated and
      modulated by protein tyrosine phosphorylation. The regulation of the levels of
      tyrosine phosphorylation is most likely the result of the coordinated actions of
      tyrosine kinases and phosphatases, which have so far been only very partially
      characterized. In the present study, we present evidence demonstrating that the
      stimulation of neutrophils by a variety of agonists (soluble as well as
      particulate) leads to the activation of the src-related tyrosine kinase lyn. The
      stimulation of tyrosine kinase activity of lyn was detected using an immune
      kinase assay as well as an in situ labeling technique. Phosphoaminoacid analysis
      of lyn indicated that the autophosphorylation of the kinase was exclusively on
      tyrosine residues. The time course of the activation of lyn is consistent with
      its playing a role in the early tyrosine phosphorylation responses of
      neutrophils. The ability of agonists with widely varying functional end responses
      to stimulate the activity of lyn indicates that this event plays a key and
      central role in the control of the activation of human neutrophils.

PMID- 7579468
TI  - Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated
      donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA
      class I identity between donor and recipient.
AB  - Between August 1985 and July 1994, we performed 115 volunteer unrelated donor
      (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86) or advanced
      phase (n = 29) chronic myeloid leukemia (CML). Standard serologic HLA typing of
      potential donors and recipients was supplemented with one-dimensional isoelectric
      focusing (IEF) for class I proteins, allogenotyping for DR and DQ alleles using
      DNA restriction fragment length polymorphism (RFLP) analysis, and the measurement
      of antirecipient major histocompatibility complex (MHC) cytotoxic T-lymphocyte
      precursor cells in the donors' blood (CTLp assay). Recipients were conditioned
      for transplantation with a combination of high-dose chemotherapy and total body
      irradiation (n = 103) or high-dose chemotherapy alone (n = 12). Twenty eight
      recipients received ex vivo T-cell-depleted marrow, and 84 underwent some form of
      in vivo T-cell depletion. The probability of severe (grades III or IV) acute
      graft-versus-host disease (aGVHD) was 24%, and that of extensive chronic graft
      versus-host disease (cGVHD), 38%. Proportional hazards regression analysis showed
      an association between low frequency CTLp and a reduced incidence of severe aGVHD
      (relative risk [RR], 0.28; P = .0035). The probability of relapse at 3 years was
      23%, with first chronic phase disease being independently associated with a lower
      risk of relapse (RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at
      3 years was 37%; the LFS for the first chronic phase and advanced phase
      recipients was 41% and 26%, respectively. First chronic phase disease (RR, 0.56;
      P = .063) and the combination of recipient cytomegalovirus (CMV) seronegativity
      and an IEF-matched donor (RR, 0.48; P = .011) were both associated with improved
      LFS. The probabilities of survival and LFS for patients under 40 years of age
      transplanted in first chronic phase from an IEF-matched donor were 73% and 50%,
      respectively. We conclude that VUD BMT is a reasonable option for patients with
      CML; when using ex vivo or in vivo T-cell depletion, optimal results are achieved
      in patients transplanted in chronic phase with marrow from donors without
      demonstrable class I HLA mismatch and a low CTLp frequency.

PMID- 7579469
TI  - A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative
      blood products for the prevention of transfusion-associated CMV infection after
      marrow transplant.
AB  - We performed a prospective, randomized trial in CMV seronegative marrow
      recipients to determine if filtered blood products were as effective as CMV
      seronegative blood products for the prevention of transfusion-transmitted CMV
      infection after marrow transplant. Before transplant, 502 patients were
      randomized to receive either filtered or seronegative blood products. Patients
      were monitored for the development of CMV infection and tissue-documented CMV
      disease between days 21 and 100 after transplant. Infections occurring after day
      21 from transplant were considered related to the transfusion of study blood
      products and, thus, were considered evaluable infections for the purpose of this
      trial. In the primary analysis of evaluable infections, there were no significant
      differences between the probability of CMV infection (1.3% v 2.4%, P = 1.00) or
      disease (0% v 2.4%, P = 1.00) between the seronegative and filtered arms,
      respectively, or probability of survival (P = .6). In a secondary analysis of all
      infections occurring from day 0 to 100 post-transplant, although the infection
      rates were similar, the probability of CMV disease in the filtered arm was
      greater (2.4% v 0% in the seronegative arm, P = .03). However, the disease rate
      was still within the prestudy clinically defined acceptable rate of < or = 5%. We
      conclude that filtration is an effective alternative to the use of seronegative
      blood products for prevention of transfusion-associated CMV infection in marrow
      transplant patients.

PMID- 7579471
TI  - Graft failure after an umbilical cord blood transplant in a patient with severe
      aplastic anemia.

PMID- 7579470
TI  - Thalidomide as salvage therapy for chronic graft-versus-host disease.
AB  - Thalidomide has been reported to be an effective agent for treatment of chronic
      graft-versus-host disease (CGVHD). To determine the efficacy of this agent in
      patients with refractory CGVHD a total of 80 patients who failed to respond to
      prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide.
      Sixteen patients (20%) had a sustained response, 9 with a complete remission and
      7 with a partial response. Twenty-nine patients (36%) had thalidomide
      discontinued because of side effects, which included sedation, constipation,
      neuritis, skin rash, and neutropenia. Side effects were reversible with drug
      discontinuation except for mild residual neuritis in one case. Rashes and
      neutropenia have not previously been reported as thalidomide side effects when
      used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active
      in the treatment of CGVHD. A high incidence of reversible side effects limited
      dose intensity and reduced the number of patients who could benefit from
      treatment.

PMID- 7579472
TI  - Hepatitis C virus infection and lymphoproliferative disorders.

PMID- 7579473
TI  - FK506 in bone marrow transplantation.

PMID- 7579474
TI  - Compensated hemolytic anemia.

PMID- 7579475
TI  - Therapy-related acute leukemia associated with t(11q23) after primary acute
      myeloid leukemia with t(8;21): a report of two cases.

PMID- 7579476
TI  - A review of the role of the agonist/antagonist muscle pairs ratio in
      rehabilitation.
AB  - Based on a review of the literature, this article analyses the application of
      measurement of the agonist/antagonist ratio of muscular strength in functional
      rehabilitation. According to many authors this ratio constitutes an element of
      functional specificity of a joint, but it is subject to numerous factors of
      variation: the joint considered, dominance, sex, age, physical activity and
      velocity of movement. Despite these various factors, the ratio may constitute a
      clinical element in the functional analysis of the joint, providing either an
      index of the risk of developing certain traumatic sports lesions, or a guide
      control in the modalities of rehabilitation.

PMID- 7579477
TI  - Gait and activity in the elderly: implications for community falls-prevention and
      treatment programmes.
AB  - Falls are the major cause of accidents in the elderly. Falls result from the
      interaction of medical, psychosocial and age-related changes with environmental
      conditions. Since many of these factors are amenable to change, theoretically
      many falls are preventable. As part of a multi-method community fall prevention
      programme we developed a gait assessment method (ELGAM). We report here on the
      association between ELGAM parameters and measures of social and physical
      activity, tested among 36 elderly community-dwelling persons. Social and physical
      activity were associated with only some of the gait parameters (turning head
      while walking and walking speed). However, the findings about gait are consistent
      with other research based on larger samples, and some of the findings from
      intervention research. Together they suggest the importance of social and
      physical activity in fall prevention programmes.

PMID- 7579478
TI  - An empirical investigation of the 'Biopsychosocial Disease Consequence model':
      psychological impairment, disability and handicap in chronic pain patients.
AB  - The purpose of this study is to emphasize the meaningfulness of a global,
      functional rather than a narrow medical view in the efficacy evaluation of
      chronic pain treatment. Therefore, the 'Biopsychosocial Disease Consequence
      (BPSDC) model' to assess function more globally than before, is presented in this
      article. The model is based on two theories: (1) the biopsychosocial approach and
      (2) WHO's classification of impairments, disabilities and handicaps. In addition
      to the presentation of the conceptual model, the development of the hypothetical
      criteria and assessment models for psychological impairments, disabilities and
      handicaps, and the validity testing of the psychological assessment axis are
      described. Within each of the three classes, i.e. psychological impairments,
      disabilities and handicaps, the results supported the independence of the
      hypothetical criteria from each other. On the other hand, results suggested that
      some changes to the hypothetical assessment models for some of the criteria might
      be valuable. It was concluded that although the most adequate psychological
      assessment models for function, found in this study, can be considered as robust
      and recommendable as one set of tools for functional assessment, the main aim of
      this article is to encourage multidisciplinary team efforts to develop and
      systematize the assessment procedures of function in patients suffering from
      chronic diseases.

PMID- 7579479
TI  - Primary visual memory of stroke patients.
AB  - This matched control group study assesses primary visual memory of stroke
      patients using the GEMAT visual-memory test. Primary visual memory of 29 stroke
      patients who scored 24 or more on the MMSE was compared with that of 33 age and
      sex-matched controls. Patients were recruited from physiotherapy outpatient
      clinics. Measured variables were the total time needed to complete the test (GTT)
      and the number of correct answers (GCA). Patients were slower (p < 0.01) and made
      more mistakes (p < 0.01) than controls. 'Young' (60-71) subjects made fewer
      mistakes (p < 0.01) than old subjects (72-89) and patients who scored 24-26 on
      MMSE were slower than patients who scored 27-30. It should be taken into
      consideration that stroke patients whose cognitive function is within a normal
      range of the MMSE might have impaired primary visual memory.

PMID- 7579480
TI  - Age-related changes of water and fat content in muscles estimated by magnetic
      resonance (MR) imaging.
AB  - The pixel values in fat/water suppression magnetic resonance (MR) images were
      measured for the thigh muscles of 18 healthy volunteers to investigate age
      related changes in muscle water and fat content. Prior to the human studies the
      reproducibility of the data was confirmed using phantoms. The standard deviations
      (SDs) of the pixel values for one of the phantoms examined five times were found
      to be within a relatively narrow range. Both the pixel values in the fat
      suppression images (PV1) and the pixel values in the water suppression images
      (PV2) of all muscles tended to be higher in the oldest group. The results
      indicate that the water and fat content of skeletal muscles is higher in aged
      persons. Moreover, the PV1 in the non-dominant limbs was found to be increased in
      the extensor muscles of the knee joints, while the PV2 in the non-dominant limbs
      did not show a significant difference, except for the rectus femoris.

PMID- 7579481
TI  - Physically disabled and frail elderly: assessing their external environments.
AB  - The study reported here forms part of a 2-year government-funded research project
      concerned with the mobility problems of physically disabled, blind and frail
      elderly in their external environment. The research grew out of a set of ideas,
      formulated by Central Government in Wales, which suggested that the Principality
      has a higher proportion of disabled people than England, Scotland or Northern
      Ireland, and that of the particularly extreme nature of the Welsh terrain
      probably presented serious difficulties to these categories of people as they
      attempted to move around in their external environments. Although difficulties
      experienced by respondents in this study can be partly attributed to their
      physical disabilities even elderly people, who were reasonably able-bodied,
      reported problems in moving around in their local areas. Some of the barriers to
      mobility, described in this project, are a function of existing legislation not
      being enforced, while others require new legislation to be enacted.

PMID- 7579482
TI  - The assessment of handicap: an evaluation of the Environmental Status Scale.
AB  - The assessment and measurement of disability and handicap are of particular
      relevance in rehabilitation, as these are the main foci of therapeutic
      intervention. The area of handicap is the least developed with few measuring
      tools to provide an objective assessment of status. The Environmental Status
      Scale (ESS) is now becoming increasingly utilized to measure handicap. It was
      used in a study of 50 patients on admission and discharge in a
      neurorehabilitation unit, to analyse its validity and usefulness as an outcome
      measure of the rehabilitation process. The results suggest it has limited
      validity, mixes disability and handicap issues and in some sections has a
      misleading scoring system. It requires modification to overcome these
      difficulties.

PMID- 7579483
TI  - Breast cancer stage at diagnosis: Caucasians versus Afro-Americans.
AB  - In the Department of Defense health care system, all women have the same ability
      to access health care. Thus, there should be no racial differences in stage at
      diagnosis solely based on ability to seek health care. A retrospective review of
      breast cancer cases from 1976-1992 was conducted to determine if there were any
      differences in stage at diagnosis between Caucasian and Afro-American females.
      Data was available for 6414 Caucasian and 746 Afro-American females. Stage at
      diagnosis was similar for both groups. However, Afro-Americans had fewer tumors <
      or = 1.0 cm than Caucasians. Afro-American females were younger (median age 50
      years versus 58 years in Caucasians). Twenty-four per cent of Afro-Americans were
      < 40 years old compared to only 9% Caucasians. When access to care is not an
      issue, there are no racial differences in stage of breast cancer at diagnosis.

PMID- 7579485
TI  - Cutaneous side effects in breast cancer patients treated with cytostatic
      polychemotherapy and rh GM-CSF: immune phenomena or drug toxicity?
AB  - The application of recombinant colony stimulating factors for chemotherapy
      induced granulocytopenia is becoming common in clinical oncology. Here we report
      on localized cutaneous side effects after subcutaneous administration of
      recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) in
      11 patients with breast cancer receiving cytostatic treatment. Seven patients
      suffering from inflammatory breast cancer received cytostatic chemotherapy with
      mitoxantrone/cyclophosphamide, whereas four patients suffering from
      noninflammatory breast cancer received high-dose epirubicin/cyclophosphamide,
      respectively. rh GM-CSF was applicated subcutaneously in a dose of 5
      micrograms/kg/d for at least ten days. In all patients, sharply demarked,
      maculous itching and burning erythemas restricted to the injection sites occurred
      after three to four injections of rh GM-CSF. These eruptions cleared within 2 to
      3 weeks, but reappeared after reexposure to rh GM-CSF. In contrast to previous
      sporadic reports, no generalized erythemas were observed. Because of this
      unexpected and subjectively intolerable side effect, rh GM-CSF administration had
      to be interrupted in all patients. Histopathological findings revealed skin
      infiltration with lymphocytes, monocytes/macrophages, neutrophils, and
      occasionally eosinophils, respectively. Since GM-CSF is known to alter immune
      functions, it seems likely that the eruptions were at least in part due to local
      immune reactions.

PMID- 7579484
TI  - Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro:
      relationship to peroxides and vitamin-E.
AB  - Epidemiological studies suggest a causal relationship of dietary polyunsaturated
      fatty acids (PUFA's) with the morbidity and mortality from breast cancer. In
      order to reveal possible underlying mechanisms of these findings, we studied the
      influence of n-3 and n-6 PUFA's in comparison to oleic acid on the proliferation
      of well characterized estrogen dependent (MCF-7, ZR-75, T-47-D) and estrogen
      independent (MDA-MB-231, HBL-100) breast cancer cells in culture. The cell growth
      inhibitory effect was related to the formation of lipid peroxidation products.
      Normal human skin fibroblasts served as a control. In fibroblasts, the addition
      of 20 micrograms/ml of exogenous fatty acids either had no effect or caused an
      insignificant increase of proliferation. Similar results were obtained with MCF-7
      cells. In all other breast cancer cell types, n-3 long-chain PUFA's,
      eicosapentaenoic and docosahexaenoic acids, were the most effective fatty acids
      in arresting the cell growth. Alpha-linolenic and gamma-linolenic acid exerted a
      variable effect on cell proliferation depending on the cell line investigated.
      Oleic acid significantly stimulated the proliferation of hormone-independent
      breast cancer cells while it had no effect on the proliferation of hormone
      dependent cells. Viability studies by trypan blue excretion indicated that the
      arrest in cell growth was not due to major cytotoxic effects. The addition of
      PUFA's to breast cancer cells caused a significant increase in the formation of
      conjugated dienes and lipid hydroperoxides in the cellular lipids; their content
      was significantly correlated with the capacity of arresting cell growth. In
      contrast, the addition of PUFA's to fibroblasts did not increase lipid
      hydroperoxide formation. The addition of Vitamin E to cancer cells at a
      concentration of 10 microM to the PUFA-supplemented medium almost completely
      restored cell growth. Our data indicate that PUFA's significantly interfere with
      cell proliferation of breast cancer cells in vitro due to the formation of
      oxidation products. In addition to that, there must be other factors involved,
      most probably related to the differential metabolism of PUFA's in tumor cells.
      Our findings may have some impact on treatment and prevention of breast cancer.

PMID- 7579486
TI  - Estrogen receptors in 699 primary breast cancers: a comparison of
      immunohistochemical and biochemical methods.
AB  - BACKGROUND: Over the last few years, estrogen receptor (ER) determination by
      immunohistochemistry (ER-ICA) has been extensively used, but it still remains to
      be established whether this method can replace the standard biochemical technique
      using dextran-coated charcoal (ERDCC). PATIENTS AND METHODS: ER were determined
      by both the dextran-coated charcoal (DCC) method and immunohistochemistry (ICA)
      in 699 patients with primary breast cancer; other parameters (age, pathological T
      pT- and nodal status -pN-, progesterone receptors by DCC, proliferative index by
      ICA) were also recorded. The 'best' cut-off for ERICA was evaluated by means of
      Receiver Operating Characteristics (R.O.C.) analysis; logistic regression
      analysis was used to find adequate 'weights' for stain intensity. RESULTS AND
      CONCLUSIONS: A significant correlation was found between the two methods (p <
      0.001). R.O.C. analysis revealed that the 'best' cut-off for the ERICA score was
      45% (sensitivity 0.810, specificity 0.804). Logistic regression analysis showed
      that an ERICA score which also considers staining intensity does not add any
      useful information concerning ER content in breast cancers.

PMID- 7579487
TI  - Vasopressin gene related products are markers of human breast cancer.
AB  - Immunohistochemical analysis for products of vasopressin and oxytocin gene
      expression was performed on acetone-fixed tissues from 19 breast cancers
      representing a variety of tumor sub-types. Studies employed the avidin-biotin
      complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal
      antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin
      associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human
      neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated
      human neurophysin (VP-HNP). Western Blot analysis was performed on protein
      extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene
      related proteins were not detected in normal breast tissue, immunohistochemistry
      revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of
      the tumor tissues examined. Vasopressin-associated human neurophysin was evident
      in only one of 19 acetone-fixed tumor preparations. However, Western blot
      analysis for all 12 fresh-frozen tumor samples showed the presence of two
      proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to
      VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to
      be common to cells of normal breast tissues. For tumors, positive staining for OT
      was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the
      tumors examined. These findings indicate that VP gene expression is a selective
      feature of all breast cancers, and that products of this expression might
      therefore be useful as markers for early detection of this disease and as
      possible targets for immunotherapy.

PMID- 7579488
TI  - Biological and clinical evaluation of lanreotide (BIM 23014), a somatostatin
      analogue, in the treatment of advanced breast cancer. A pilot study by the
      I.T.M.O. Group. Italian Trials in Medical Oncology.
AB  - Biological data support the development of clinical trials designed to evaluate
      the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC).
      Although previous clinical trials have failed to show antitumor activity, various
      factors may have biased their results. In an attempt to improve our understanding
      of the role of SMS analogues in ABC, 10 patients with favourable prognostic
      factors and who had not been heavily pretreated for advanced disease were treated
      with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were
      periodically taken to evaluate the effect of the drug on growth hormone (GH) and
      insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although
      the drug was well tolerated, no clinical activity was observed. Serum GH and IGF
      1 levels were not properly suppressed over time and drug serum concentrations
      fluctuated widely. In conclusion, SMS analogues cannot be recommended even as
      palliative treatment of ABC. Further studies should be undertaken to investigate
      the effect of higher drug doses, given subcutaneously or by means of continuous
      infusion, in suppressing GH and IGF-1 serum levels.

PMID- 7579489
TI  - CA15-3, CASA, MSA, and TPS as diagnostic serum markers in breast cancer.
AB  - This is the first comparison of the three mucin based tests CA15-3, CASA, and
      MSA, and the cytokeratin-related TPS assay in breast cancer. The mucin markers
      were superior to TPS in receiver-operator analysis, though no marker was of use
      in the diagnosis of malignancy due to low sensitivity. Using cutpoints that gave
      95% specificity in benign disease (n = 83), corresponding sensitivities in pre
      treatment breast cancer (n = 123: 13 in situ, 54 stage I, 45 stage II, 4 stage
      III, 7 stage IV) were 17% (CA15-3), 16% (CASA), 13% (MSA), and 8% (TPS), with a
      strong relationship between marker levels and disease stage. These assays did not
      always detect the same patients, and the use of CA15-3 combined with CASA gave
      the highest sensitivity (23%), though this was not significantly better than the
      use of CA15-3 alone. Despite detecting similar antigens, these assays can show
      markedly different responses in some patients, indicating that one mucin-based
      test cannot be substituted for another.

PMID- 7579490
TI  - Maintenance of DNA content and erbB-2 alterations in intraductal and invasive
      phases of mammary cancer.
AB  - Ductal carcinoma in situ (intraductal carcinoma) of the breast is a commonly
      recognized and curable clinical entity. Patients with intraductal carcinoma are
      at risk to develop invasive breast cancer presumably due to a transition from the
      noninvasive to the invasive phase of growth. Primary breast malignancies commonly
      display both in situ and invasive phases of growth in the same tumor. In the
      current study, DNA content and alterations in the erbB-2 (HER-2/neu) oncogene
      product were examined simultaneously in both growth phases of primary breast
      cancers by image analysis. DNA content in the intraductal and invasive components
      of primary breast cancers were virtually identical (r = 0.979, p < 0.001).
      Quantitative image analysis was used to measure erbB-2 expression and categories
      of expression were related to copy number of the erbB-2 gene. Expression of erbB
      2 was similar in both growth phases and implies identity of the erbB-2 genotype.
      The identity of DNA content suggests that the noninvasive and invasive phases
      within a single breast cancer are highly related. It is likely that erbB-2 gene
      number remains the same during progression from intraductal to invasive disease.

PMID- 7579491
TI  - Relationship of growth stimulated by lithium, estradiol, and EGF to phospholipase
      C activity in MCF-7 human breast cancer cells.
AB  - Lithium-stimulated MCF-7 cell proliferation was compared to proliferation
      stimulated by other mitogens for this cell line-estradiol (E2) and epidermal
      growth factor (EGF)-and lithium was found to be effective within a narrow
      concentration range. Mitogenic effects of lithium on proliferation stimulated by
      E2 and EGF were additive below maximum, but were not synergistic. The
      phosphoinositide pathway is a cell signaling system involved in cell
      proliferation, within which phospholipase C (PLC)-mediated hydrolysis of
      phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] leads to the production of
      the second messengers inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] and
      diacylglycerol (DAG), as well as to calcium mobilization. At mitogen
      concentrations which maximally stimulated cell growth, estradiol stimulated both
      growth and PLC activity, while EGF and lithium stimulated cell growth but had
      little effect on the activity of the enzyme. Dose-responses with EGF revealed
      that a low concentration (0.1 ng/ml, 0.017 nM) of EGF appeared to stimulate both
      PLC activity and cell growth, but that higher concentrations of EGF which
      stimulated greater proliferation inhibited PLC activity. Steady-state levels of
      inositol phosphates including inositol trisphosphate were increased by all three
      mitogens. In growth assays, the phorbol ester phorbol 12-myristate-13-acetate
      (PMA), which mimics the actions of DAG, stimulated some cell growth, but
      dioctanoylglycerol, an additional DAG analog, and the calcium ionophore A23187,
      alone or with the DAG analogs, had no effect. These results suggest that PLC
      mediated PtdIns(4,5)P2 hydrolysis is not primarily associated with signaling
      proliferation by lithium or EGF in MCF-7 breast cancer cells.

PMID- 7579492
TI  - Effect of timing of surgery during the menstrual cycle of premenopausal breast
      cancer patients.
AB  - BACKGROUND: In 1989 it was suggested that the timing of surgery during follicular
      or corpus luteum phase of the menstrual cycle could substantially influence the
      survival time in premenopausal breast-cancer patients [1]. Several researchers
      analysed their data, but in general they could not confirm this observation.
      Nevertheless, two other reports in that series found some influence of the time
      of surgery during menstrual cycle on prognosis, although, they suggested
      different time periods as favourable [8, 9]. PURPOSE: The purpose of this study
      was to investigate the effect of timing of surgery in a study population which
      was much larger than the previous studies. METHOD: All premenopausal patients
      with primary breast cancer who had been operated at one clinic between 1st of
      January 1980 and 31st of December 1990 were considered eligible for the study.
      Based on the day of surgery during the menstrual cycle all patients were grouped
      according to three proposed categories and to an additional one which consisted
      of the favourable days from the three proposed categories. We investigated the
      effects of several prognostic factors and of the timing of surgery on three
      endpoints: recurrence free survival, distant disease free survival, and overall
      survival. RESULTS: The traditional prognostic factors had effects in agreement
      with the literature. Of the different categories for timing of surgery none had a
      significant influence; the strongest in univariate analysis had a p-value of 0.10
      and the trend was in the opposite direction to the one proposed in the
      literature. These results did not change in multivariate analysis with the Cox
      model. CONCLUSIONS: Timing of surgery does not have an important effect on the
      prognosis of breast cancer patients. Incorporating other results from the
      literature, we conclude that it has at most a weak effect. IMPLICATIONS: At
      present there is no need to incorporate the day of menstrual cycle in the
      planning of surgery for premenopausal breast cancer patients.

PMID- 7579495
TI  - Aromatase inhibition with 4-OHAndrostenedione after prior aromatase inhibition
      with aminoglutethimide in women with advanced breast cancer.
AB  - One hundred and twelve post menopausal or post oophorectomy women with advanced
      breast cancer (BC) who had all previously had aminoglutethimide (AG) were treated
      with the potent aromatase inhibitor 4-hydroxy androstenedione (4-OHA). Twenty
      three women (21%) had a partial response to 4-OHA while another twenty five
      patients (22%) had stabilization of previously progressing disease. Patients
      responded to 4-OHA both after previously responding to then relapsing on, and
      after failing to respond to aminoglutethimide. Toxicity was minimal. This study
      shows that potent aromatase inhibition with 4-OHA is effective in women with
      advanced BC who have already been treated with a less potent aromatase inhibitor,
      and suggests that relative changes in oestrogen levels may be more important than
      absolute levels.

PMID- 7579494
TI  - Phase II study of high-dose epirubicin, lonidamine, alpha 2b interferon in
      advanced breast cancer.
AB  - 44 patients with advanced breast cancer were treated with high-dose epirubicin
      (130 mg/sqm), because of its steep dose-response curve. Lonidamine and alpha
      interferon were administered as well with the aim of increasing epirubicin uptake
      and overcoming drug resistance. Granulocyte-colony stimulating factor support was
      provided. 14 complete responses and 22 partial responses were observed in 40
      evaluable patients for a 90% overall response rate. Median duration of response
      was 12 months for complete responders, 7 months for partial responders. In two
      cases the complete response has lasted for more than two years. Myelosuppression,
      infection, and cardiac toxicity were the main treatment-related toxic effects.
      These results are encouraging enough to justify a randomized comparison of our
      chemotherapy program with standard regimens used in advanced breast cancer.

PMID- 7579493
TI  - Molecular aspects of estrogen receptor variants in breast cancer.
AB  - Measurements of the estrogen receptor (ER) and the estrogen-induced progesterone
      receptor (PgR) are used by most clinicians as indicators of both overall
      prognosis and likelihood of response to endocrine therapy. Patients with ER+/PgR+
      tumors have the highest likelihood of response; conversely, patients with ER-/PgR
      tumors have the lowest likelihood of response. Unfortunately, most patients
      treated successfully with endocrine therapy eventually develop endocrine
      resistant disease recurrence. In an effort to study potential mechanisms of
      endocrine resistance, we have studied discordant ER-/PgR+ tumors, in which the
      normally estrogen-regulated PgR gene is induced in the apparent absence of ER.
      Our laboratory has previously cloned, from ER-/PgR+ tumors, a variant ER mRNA
      precisely missing the sequence corresponding to ER exon 5, and has demonstrated
      that the truncated protein product translated from this variant RNA is capable of
      constitutively inducing the expression of an estrogen-responsive reporter gene in
      a yeast expression vector system (Fuqua et al. Cancer Res 51:105-109, 1991). In
      the present report we describe further experiments to characterize the activity
      and biological consequences of expression of this variant ER in human breast
      cancer cells. We have stably transfected MCF-7 human breast cancer cells with a
      mammalian expression vector for the exon 5 deletion variant ER. These transfected
      cells produce a truncated ER protein of the expected 40 kDa size. Cells
      expressing the exon 5 ER deletion variant constitutively express PgR, and
      manifest increased anchorage-independent colony formation in the absence of
      estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579497
TI  - Nonattendance in the Stockholm mammography screening trial: relative mortality
      and reasons for nonattendance.
AB  - The first objective of this study was to analyze the survival rate in a group of
      69 breast cancers detected among nonattenders in a randomized mammographic
      screening trial in relation to 142 clinically detected cancers in a nonscreened
      control population. By analyzing the cancers of the nonattenders we identified
      two subgroups, one (A) had actively avoided mammography, had cancers in more
      advanced stages on diagnosis, and had significantly higher mortality from breast
      cancer than the control group (p = 0.003). The second subgroup (B) had
      mammography done outside the screening program. This subgroup had a
      nonsignificant, slightly better survival (p = 0.19) compared to the control
      group. Concerning stage the cancers in group B were similar to the cancers by the
      screening program. The second objective was to analyze women's reasons for
      nonattendance in the screening program. We interviewed 200 randomly selected
      nonattenders; 33% stated that they never could imaging having mammography
      (definite nonattenders), 29.5% that they for various reasons had missed the
      mammography but could imagine having it next time (possible future attenders),
      and 32% had been examined outside the program. Reasons for nonattendance included
      disinterest, medical problems, and fear of X-rays. From this interview
      investigation we believe that the subgroup of definite nonattenders (33%) is
      difficult to influence. The second subgroup classified as possible future
      attenders (29.5%) we believe can be influenced by more information and a new
      opportunity to receive mammography, i.e., a reminder letter. The third subgroup,
      those examined outside the screening program (32%) were aware of the benefit of
      mammography, taking action on their own.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579498
TI  - Increased phosphotyrosine in breast cancer tissue is associated with a worse
      prognosis.
AB  - We have previously demonstrated that phosphotyrosine can be identified in breast
      cancer cells using an immunohistochemical stain. We have subsequently used this
      technique to characterize 106 women with breast cancer (46 with Stage 1 and 60
      with Stage 2) who have been followed for at least four years by one oncologist.
      We analyzed all primary breast cancer tissue using immunohistochemical staining
      and the amount of phosphotyrosine (PT) was scored on a 0 to 3 range. The PT score
      of the primary tumor was unrelated to either breast cancer stage or estrogen and
      progesterone receptor analysis, as high PT scores were noted in both disease
      stages and all receptor categories. We did find that patients with either no or
      trace (1+) amounts of PT survived longer than those patients with higher amounts
      of PT. The patients with low PT had significantly lower chance of relapse (Chi
      Square = 15.8, p < 0.001) and a lower mortality (Chi Square = 13.1, p = 0.001).
      We conclude that immunohistochemical methods to determine the PT score may
      identify patients at higher risk for disease relapse independent of tumor stage
      or hormonal status.

PMID- 7579496
TI  - The biochemistry of breast cyst fluids and duct secretions.
AB  - The ratio of potassium to sodium concentrations in breast fluids has led other
      investigators to the subclassification of cysts into two types: 1) apocrine
      (secretory) cysts with high potassium and low sodium, and 2) attenuated
      (flattened) cell cysts with low potassium and high sodium content. Apocrine cells
      are thought by some to actively secrete potassium. Cell typing is considered
      important as apocrine cysts are more likely to be bilateral, multiple, recurrent,
      and serve as markers for epithelial cell atypia. A retrospective study of the
      biochemical analyses of 58 cyst fluids and 28 duct secretions obtained by nipple
      aspiration was conducted. Potassium and sodium concentrations obtained from 12
      cyst fluids were statistically correlated with creatinine concentrations.
      Evidence is presented indicating that micro cysts are initially apocrine in cell
      type and are more likely in continuity with the terminal ductal-lobular unit. It
      is postulated that apocrine cysts undergo cellular desquamation and lysis,
      becoming attenuated cysts. The ratio of potassium to sodium is altered by cell
      degradation rather than active secretory processes. Biochemical contents of cysts
      and nipple aspiration fluids are compared.

PMID- 7579500
TI  - Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new
      members of the epidermal growth factor family, in human breast carcinomas.
AB  - The expression of amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1) mRNA
      transcripts was assessed in 60 human primary breast carcinoma. AR and HRG
      transcripts were expressed respectively in 58% and 25% of the carcinomas as
      measured by Northern blot analysis. CR-1 mRNA was found in 77% of the carcinomas
      using Reverse Transcriptase-PCR analysis. Coexpression of two or three of these
      peptides was observed in several specimens. There was no significant association
      between AR, HRG, and CR-1 expression and nodal status, EGF receptor, or c-erbB-2
      protooncogene expression in these tumors. However, a significant association
      between AR expression and estrogen receptor positivity was observed.

PMID- 7579499
TI  - The prognostic value of c-erbB2 in primary breast carcinomas: a study on 942
      cases.
AB  - To assess the practical prognostic value of c-erbB2, we performed a study on 942
      invasive ductal carcinomas treated with primary surgery between 1980 and 1986 in
      our center. We evaluated its expression by immunohistochemistry in paraffin
      embedded tissue using a polyclonal antipeptide antibody. Of 942 tumors, 229 (24%)
      showed a positive membrane staining. We observed a significant association
      between c-erbB2 and Scarff-Bloom-Richardson grading (p < 0.0001) and a negative
      correlation between c-erbB2 and both estrogen and progesterone receptors (p <
      0.0001). In our analysis, with respect to overall survival (OS), relapse-free
      survival (RFS), and metastasis-free survival (MFS), c-erbB2 was statistically
      significant (p < or = 0.0001) for the whole group and the node-positive subgroup.
      In multivariate analysis, c-erbB2 appeared to be an independent variable for RFS
      and MFS in the node-negative group. However, in our hands, c-erbB2 had a poor
      prognostic value in comparison with the classical prognostic variables such as
      histological grade, nodal status (N), hormonal receptor status (estrogen and
      progesterone receptors), and tumor size, and it did not supersede the classical
      parameters.

PMID- 7579501
TI  - When can stereotactic core biopsy replace excisional biopsy?--A clinical
      perspective.
AB  - Stereotactic core biopsy is becoming increasingly popular as a technique which
      provides a histologic diagnosis for mammographic abnormalities while avoiding the
      trauma, deformity, and much of the cost associated with surgical biopsy. This
      review evaluates the published literature on the diagnostic accuracy of core
      biopsy for ductal carcinoma in situ and invasive breast cancer and the ability of
      core biopsy to characterize malignant lesions sufficiently to allow treatment
      planning. Issues of cost effectiveness are examined in the context of the degree
      of suspicion of the mammographic abnormality being sampled by core technique as
      well as subsequent breast cancer therapy.

PMID- 7579502
TI  - A prospective analysis of immunohistochemically determined hormone receptors and
      nuclear features as predictors of early recurrence in primary breast cancer.
AB  - The immunohistochemically determined receptor status, as well as first-generation
      risk factors (tumor size, lymph node status, histologic grading including
      subfactors, tumor histology, and biochemically determined receptor status) were
      prospectively analyzed in 288 cases of primary breast cancer for their impact on
      recurrence-free survival (RFS) and overall survival (OS) after a median
      observation period of 41 months. Immunohistochemically (ER-ICA) and biochemically
      determined estrogen receptors (ER-DCC), as well as tumor size, lymph node status,
      histologic grading, mitotic rate, and nuclear polymorphism, were of prognostic
      value for recurrence-free survival and/or overall survival. In multivariate
      analysis, lymph node status, tumor size, and mitotic rate proved to be
      independent prognosticators; ER-ICA showed significance in the univariate
      analysis which dropped, however, when multivariate analysis was applied. The
      prognostic power of histologic grading in our series seemed to depend mainly on
      the subfactors which relate to nuclear features.

PMID- 7579504
TI  - High dose toremifene for estrogen and progesterone receptor negative metastatic
      breast cancer: a phase II trial of the Cancer and Leukemia Group B (CALGB).
AB  - In pre-clinical and limited clinical studies, high doses ( > or = 200 mg/day) of
      the triphenylethylene derivative toremifene showed activity in estrogen receptor
      (ER) negative and ER-unknown metastatic breast cancer after progression on
      tamoxifen, and a mechanism of action independent of hormone receptor binding was
      speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the
      efficacy of high dose toremifene in a population of patients who had hormone
      receptor-negative, metastatic breast cancer with limited prior chemotherapy
      exposure, good performance status, and measurable disease. Twenty eligible
      patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity
      was minimal. Nausea was reported by 20% of the patients, lightheadedness by 20%,
      weight loss by 20%, and hot flashes by 15%. There was no grade 3-4 toxicity. No
      objective responses were observed, and 5 of 6 patients with stable disease at 8
      weeks developed progressive disease at 11 to 33 weeks. High dose toremifene (400
      mg/day) is well-tolerated but imparts no detectable activity in hormone receptor
      negative, metastatic breast cancer.

PMID- 7579505
TI  - Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses
      in breast cancer patients.
AB  - To evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence,
      serial serum determinations of both antigens were performed in 1023 patients
      (follow-up: 1-10 years, mean 6.2 years) with primary breast cancer (CA 15.3 in
      533 cases) and no evidence of residual disease (NED) after radical treatment
      (radical mastectomy or simple mastectomy and radiotherapy). 246 patients
      developed metastases during follow-up. RESULTS: CEA and CA 15.3 were elevated ( >
      10 ng/ml or > 60 U/ml, respectively) prior to diagnosis in 40% (98/246) and 41%
      (37/91) of the patients with recurrence, with a lead time of 4.9 +/- 2.2 and 4.2
      +/- 2.3 months, respectively. When patients with locoregional recurrences were
      excluded, sensitivity improved to 46% (CEA) and 54% (CA 15.3), and to 64% with
      both tumor markers (CEA and/or CA 15.3). Higher levels of both CEA and CA 15.3 at
      diagnosis of recurrence, higher sensitivity in early diagnosis of relapse, and a
      higher lead time were found in ER+ (CEA) or PgR+ patients (CA 15.3) than in those
      that were negative for these receptors in the primary tumor (p < 0.001).
      Specificity of the tumor markers was 99% for both CEA (777 NED patients) and for
      CA 15.3 (444 NED patients), respectively. In conclusion, CEA and CA 15.3 are
      useful tools for early diagnosis of metastases, mainly in those patients with ER+
      or PR+ tumors.

PMID- 7579503
TI  - Recurrence-free survival in breast cancer improved by adjuvant tamoxifen-
      especially for progesterone receptor positive tumors with a high proliferation.
AB  - Although the beneficial effect on breast cancer of adjuvant tamoxifen (TAM) is
      well established, in the series studied by our group this effect seems to have
      been restricted to patients with steroid receptor (especially progesterone
      receptor (PgR)) positive tumors. However, as some patients with PgR-positive
      tumors manifested recurrence despite adjuvant TAM treatment, the question arose
      whether some other biological factor(s) could be used to identify these non
      responding cases. The level of the S-phase fraction (SPF), as measured by flow
      cytometry, has been shown to be a useful prognostic marker, prognosis being
      better in cases where the SPF is low than in those where it is high. The aim of
      the present study was to relate the prognosis after adjuvant TAM to SPF among
      patients with PgR-positive tumors. In the PgR-positive group as a whole, the
      effect of TAM on prognosis was more pronounced in the high SPF group than in the
      low SPF group (p = 0.005) the respective decrease in 3 year recurrence rate was
      from 19 to 43% and from 17 to 9%. Multivariate analysis of the data for the TAM
      treated group showed the level of PgR concentration (low positive vs. high
      positive), lymph node status, and tumor size to be independent predictive
      factors, but not the level of SPF (i.e. high vs. low). By contrast, among
      patients not treated with TAM, the SPF was a strong independent prognostic
      factor. To sum up, SPF was a strong independent predictor of outcome only for
      patients receiving no systemic adjuvant therapy, but not in patients receiving
      adjuvant TAM. Patients with PgR-positive and high S-phase tumors derived more
      benefit from TAM than patients with PgR-positive and low SPF tumors.

PMID- 7579506
TI  - Adjuvant tamoxifen for pre- and postmenopausal women with estrogen receptor
      positive, node positive breast cancer: a randomized study.
AB  - 370 patients with operable, axillary node positive breast cancer, were randomized
      to receive tamoxifen (TAM) 20 mg/day for 2 years or no adjuvant hormone therapy.
      All patients had estrogen receptor (ER) positive (ER > 10 pmol/g) primary
      tumours. 350 patients, 93 younger than 50 years of age and 257 patients 50 years
      or older, were evaluable for the study. After a median follow up of 76 months,
      significantly (p = 0.0001) fewer loco-regional, but not distant (systemic),
      relapses have been recorded in the TAM group. Overall survival was also improved,
      but even though the study was designed to give maximum benefit from TAM
      statistically significant effect of TAM seemed to be limited to patients 50 years
      of age and older.

PMID- 7579507
TI  - At convenience and systematic random sampling: effects on the prognostic value of
      nuclear area assessments in breast cancer patients.
AB  - This study compares the influence of two different nuclear sampling methods on
      the prognostic value of assessments of mean and standard deviation of nuclear
      area (MNA, SDNA) in 191 consecutive invasive breast cancer patients with long
      term follow up. The first sampling method used was 'at convenience' sampling
      (ACS); the second, systematic random sampling (SRS). Both sampling methods were
      tested with a sample size of 50 nuclei (ACS-50 and SRS-50). To determine whether,
      besides the sampling methods, sample size had impact on prognostic value as well,
      the SRS method was also tested using a sample size of 100 nuclei (SRS-100). SDNA
      values were systematically lower for ACS, obviously due to (unconsciously) not
      including small and large nuclei. Testing prognostic value of a series of cut off
      points, MNA and SDNA values assessed by the SRS method were prognostically
      significantly stronger than the values obtained by the ACS method. This was
      confirmed in Cox regression analysis. For the MNA, the Mantel-Cox p-values from
      SRS-50 and SRS-100 measurements were not significantly different. However, for
      the SDNA, SRS-100 yielded significantly lower p-values than SRS-50. In
      conclusion, compared with the 'at convenience' nuclear sampling method,
      systematic random sampling of nuclei is not only superior with respect to
      reproducibility of results, but also provides a better prognostic value in
      patients with invasive breast cancer.

PMID- 7579509
TI  - Prognostic value of p53 in breast invasive ductal carcinoma: an
      immunohistochemical study on 942 cases.
AB  - P53 immunohistochemical detection using DO7 antibody on 942 cases of previously
      untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9
      months (89 to 160) was performed. Three hundred and three (32%) tumors were
      positive. All positive tumors were taken into account, positivity ranging from 1
      to 100% of tumoral cells. The Chi square test showed significant negative
      correlation between p53 positivity and age (p = 0.01), estrogen receptor status
      (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant
      positive correlation with tumor grade according to the Scarff, Bloom and
      Richardson system (SBR Grade) (p < 0.0001). There was no significant association
      with tumor size or nodal status. Concerning the univariate analysis, in the whole
      group and node-positive group (n = 544) p53 positivity was highly significant for
      overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p
      = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p =
      0.0003). In the node-negative group (n = 398), p53 was significant with respect
      to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent
      prognostic parameter in the multivariate analysis in the whole group and the node
      positive group, though of minor significance compared to axillary lymph node
      status, SBR grade, progesterone receptor status and tumor size.

PMID- 7579508
TI  - P-glycoprotein immunostaining correlates with ER and with high Ki67 expression
      but fails to predict anthracycline resistance in patients with advanced breast
      cancer.
AB  - In an attempt to further define the clinical utility of p-glycoprotein
      immunostaining in breast cancer, we examined 101 specimens from patients with
      advanced breast cancer. There was a significant correlation between estrogen
      receptor status and p-glycoprotein expression but only for low levels of p
      glycoprotein. Premenopausal status appeared to correlate with increased p
      glycoprotein expression, but this probably reflects patient selection as
      premenopausal patients had higher prior exposure to anthracyclines and were more
      likely to have received chemotherapy as initial treatment. P-glycoprotein
      expression was highly significantly correlated with expression of the
      proliferation related antigen Ki67, suggesting that p-glycoprotein expression may
      well be cell cycle dependent, with overexpression occurring in rapidly cycling
      cells. These findings may explain reported findings of modulation of p
      glycoprotein expression by agents such as anti-oestrogens. P-glycoprotein
      positive staining did not, however, predict chemotherapy treatment failure or
      survival duration.

PMID- 7579510
TI  - Improved prognostication in small (pT1) breast cancers by image cytometry.
AB  - Feulgen-stained samples from 460 small (pT1) primary breast cancers were
      investigated by means of an image analysis system. Several DNA, morphometrical
      and textural parameters were evaluated for each patient, and the prognostic
      meaning of these parameters was then investigated by the Cox regression analysis.
      As prognostic criterion a distant recurrence-free survival of five years was
      considered. All investigated DNA- and morphometrical parameters as well as
      several textural parameters showed a significant univariate correlation with the
      clinical course. In a multivariate approach the axillary nodal status was the
      most important prognostic parameter, followed by a morphometric parameter
      (anisokaryosis) and two textural parameters (runlength and co-occurrence). None
      of the DNA histogram derived parameters could add prognostic information in this
      multivariate approach. By the linear combination of the four selected variables,
      an individual prognostic factor was calculated. Using this factor the patients
      could be split into several groups according to their risk for distant
      metastases. Thus a low risk group of pT1 patients could be identified with a
      distant recurrence rate of only 2% after 5 years, and also a group of patients
      with a considerably worse prognosis and a 5-year distant recurrence rate of 53%.
      In contrast, using the nodal status as single parameter allows the identification
      of a low risk group of patients (pN0pT1) with a distant recurrence rate of 10.6%.
      Therefore, morphometrical and textural parameters can provide powerful prognostic
      information in small breast carcinomas and may allow a better selection of
      patients for adjuvant therapy.

PMID- 7579511
TI  - Prognostic significance of heat-shock protein-27 in node-positive breast
      carcinoma: an immunohistochemical study.
AB  - Immunostaining for heat-shock protein-27 (HSP-27) was performed on formalin fixed
      paraffin embedded sections of 890 node-positive breast carcinomas resected
      between 1980 and 1986. The follow-up ranged from 2.5 to 10.5 years. A polyclonal
      antibody (Hu27, dilution: 1/200) was used. A positive cytoplasmic staining was
      obtained in 383 cases (43%). No difference in distant metastasis-free survival
      (DMFS) or overall survival (OS) was noted between cases with positive or negative
      immunostaining. This study suggests that HSP-27 expression is not predictive of
      the outcome in node-positive breast cancer.

PMID- 7579512
TI  - The evolution of vertebrate gastrulation.
AB  - The availability of molecular markers now permits the analysis of the common
      elements of vertebrate gastrulation. While gastrulation appears to be very
      diverse in the vertebrates, by analyzing a head-organizer marker, goosecoid, and
      a marker common to all forming mesoderm, Brachyury, we attempt to identify
      homologous structures and equivalent stages in Xenopus, zebrafish, chick and
      mouse gastrulation. Using a tail-organizer marker, Xnot-2, we also discuss how
      the late stages of gastrulation lead to the formation of the postanal tail, a
      structure characteristic of the chordates.

PMID- 7579513
TI  - Gene duplications and the origins of vertebrate development.
AB  - All vertebrates possess anatomical features not seen in their closest living
      relatives, the protochordates (tunicates and amphioxus). Some of these features
      depend on developmental processes or cellular behaviours that are again unique to
      vertebrates. We are interested in the genetic changes that may have permitted the
      origin of these innovations. Gene duplication, followed by functional divergence
      of new genes, may be one class of mutation that permits major evolutionary
      change. Here we examine the hypothesis that gene duplication events occurred
      close to the origin and early radiation of the vertebrates. Genome size
      comparisons are compatible with the occurrence of duplications close to
      vertebrate origins; more precise insight comes from cloning and phylogenetic
      analysis of gene families from amphioxus, tunicates and vertebrates. Comparisons
      of Hox gene clusters, other homeobox gene families, Wnt genes and insulin-related
      genes all indicate that there was a major phase of gene duplication close to
      vertebrate origins, after divergence from the amphioxus lineage; we suggest there
      was probably a second phase of duplication close to jawed vertebrate origins.
      From amphioxus and vertebrate homeobox gene expression patterns, we suggest that
      there are multiple routes by which new genes arising from gene duplication
      acquire new functions and permit the evolution of developmental innovations.

PMID- 7579514
TI  - Temporal colinearity and the phylotypic progression: a basis for the stability of
      a vertebrate Bauplan and the evolution of morphologies through heterochrony.
AB  - Vertebrate Hox genes are essential for the proper organization of the body plan
      during development. Inactivation of these genes usually leads to important
      alterations, or transformations, in the identities of the affected developing
      structures. Hox genes are activated in a progressive temporal sequence which is
      colinear with the position of these genes on their respective complexes, so that
      'anterior' genes are activated earlier than 'posterior' ones (temporal
      colinearity). Here, an hypothesis is considered in which the correct timing of
      activation of this gene family is necessary in order to properly establish the
      various expression domains. Slight modifications in the respective times of gene
      activation (heterochronies) may shift expression domains along the rostrocaudal
      axis and thus induce concurrent changes in morphologies. It is further argued
      that temporal colinearity only occurs in cells with high mitotic rates, which
      results in a strong linkage between patterning and growth control and makes the
      patterning process unidirectional, from anterior, proximal and early, to
      posterior, distal and late, a model referred to as the 'Einbahnstrasse'. While
      the nature of the mechanism(s) behind temporal and spatial colinearities is
      unknown, it is proposed that such a mechanism relies on meta-cis interactions,
      that is it may necessitate gene contiguity. Such a mechanism would be based on
      DNA-specific, rather than gene-specific, features such as chromatin
      configurations or DNA replication. The existence of such a meta-cis mechanism
      would explain the extraoridinary conservation of this genetic system during
      evolution as its basic properties would be linked to that of the genetic material
      itself.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579517
TI  - Evolutionary developmental biology of the tetrapod limb.
AB  - New insights into the origin of the tetrapod limb, and its early development and
      patterning, are emerging from a variety of fields. A wide diversity of approaches
      was reported at the BSDB Spring Symposium on 'The Evolution of Developmental
      Mechanisms' (Edinburgh, 1994); here I review the contributions these various
      approaches have made to understanding the evolutionary developmental biology of
      the tetrapod limb. The fields covered included palaeontology, descriptive
      embryology, experimental embryological analysis of interactions within developing
      limbs plus description and manipulation of homeobox gene expression in early limb
      buds. Concepts are equally varied, sometimes conflicting, sometimes overlapping.
      Some concern the limb 'archetype' (can the palaeontologists and morphologists
      still define this with precision? how far is there a limb developmental
      bauplan?); others are based on identification of epigenetic factors (eg secondary
      inductions), as generating pattern; while yet others assume a direct gene
      morphology relationship. But all the contributors ask the same compelling
      question: can we explain both the similarity (homology) and variety of tetrapod
      limbs (and the fins of the Crossopterygians) in terms of developmental
      mechanisms?

PMID- 7579516
TI  - Gene loss and gain in the evolution of the vertebrates.
AB  - Homeobox cluster genes (Hox genes) are highly conserved and can be usefully
      employed to study phyletic relationships and the process of evolution itself. A
      phylogenetic survey of Hox genes shows an increase in gene number in some more
      recently evolved forms, particularly in vertebrates. The gene increase has
      occurred through a two-step process involving first, gene expansion to form a
      cluster, and second, cluster duplication to form multiple clusters. We also
      describe data that suggests that non-Hox genes may be preferrentially associated
      with the Hox clusters and raise the possibility that this association may have an
      adaptive biological function. Hox gene loss may also play a role in evolution.
      Hox gene loss is well substantiated in the vertebrates, and we identify
      additional possible instances of gene loss in the echinoderms and urochordates
      based on PCR surveys. We point out the possible adaptive role of gene loss in
      evolution, and urge the extension of gene mapping studies to relevant species as
      a means of its substantiation.

PMID- 7579518
TI  - The origin of vertebrate limbs.
AB  - The earliest tetrapod limbs are polydactylous, morphologically varied and do not
      conform to an archetypal pattern. These discoveries, combined with the
      unravelling of limb developmental morphogenetic and regulatory mechanisms, have
      prompted a re-examination of vertebrate limb evolution. The rich fossil record of
      vertebrate fins/limbs, although restricted to skeletal tissues, exceeds the
      morphological diversity of the extant biota, and a systematic approach to limb
      evolution produces an informative picture of evolutionary change. A composite
      framework of several phylogenetic hypotheses is presented incorporating living
      and fossil taxa, including the first report of an acanthodian metapterygium and a
      new reconstruction of the axial skeleton and caudal fin of Acanthostega gunnari.
      Although significant nodes in vertebrate phylogeny remain poorly resolved, clear
      patterns of morphogenetic evolution emerge: median fin origination and
      elaboration initially precedes that of paired fins; pectoral fins initially
      precede pelvic fin development; evolving patterns of fin distribution, skeletal
      tissue diversity and structural complexity become decoupled with increased
      taxonomic divergence. Transformational sequences apparent from the fish-tetrapod
      transition are reiterated among extant lungfishes, indicating further directions
      for comparative experimental research. The evolutionary diversification of
      vertebrate fin and limb patterns challenges a simple linkage between Hox gene
      conservation, expression and morphology. A phylogenetic framework is necessary in
      order to distinguish shared from derived characters in experimental model
      regulatory systems. Hox and related genomic evolution may include convergent
      patterns underlying functional and morphological diversification. Brachydanio is
      suggested as an example where tail-drive patterning demands may have converged
      with the regulation of highly differentiated limbs in tetrapods.

PMID- 7579515
TI  - Developmental expression of the mouse Evx-2 gene: relationship with the evolution
      of the HOM/Hox complex.
AB  - The mouse Evx-2 gene is located in the immediate vicinity of the Hoxd-13 gene,
      the most posteriorly expressed gene of the HOXD complex. While the Evx-1 gene is
      also physically linked to the HOXA complex, it is more distantly located from the
      corresponding Hoxa-13 gene. We have analysed the expression of Evx-2 during
      development and compared it to that of Evx-1 and Hoxd-13. We show that, even
      though Evx-2 is expressed in the developing CNS in a pattern resembling that of
      other Evx-related genes, the overall expression profile is similar to that of the
      neighbouring limbs and genitalia. We propose that the acquisition of expression
      features typical of Hox genes, together with the disappearance of some expression
      traits common to Evx genes, is due to the close physical linkage of Evx-2 to the
      HOXD complex, which results in Evx-2 expression being partly controlled by
      mechanisms acting in the HOX complex. This transposition of the Evx-2 gene next
      to the Hoxd-13 gene may have occurred soon after the large scale duplications of
      the HOX complexes. A scheme is proposed to account for the functional evolution
      of eve-related genes in the context of their linkage to the HOM/Hox complexes.

PMID- 7579519
TI  - Hox genes and growth: early and late roles in limb bud morphogenesis.
AB  - In recent years, molecular analysis has led to the identification of some of the
      key genes that control the morphogenesis of the developing embryo. Detailed
      functional analysis of these genes is rapidly leading to a new level of
      understanding of how embryonic form is regulated. Understanding the roles that
      these genes play in development can additionally provide insights into the
      evolution of morphology. The 5' genes of the vertebrate Hox clusters are
      expressed in complex patterns during limb morphogenesis. Various models suggest
      that the Hoxd genes specify positional identity along the anteroposterior (A-P)
      axis of the limb. Close examination of the pattern of Hoxd gene expression in the
      limb suggests that a distinct combination of Hoxd gene expressed in different
      digit primordia is unlikely to specify each digit independently. The effects of
      altering the pattern of expression of the Hoxd-11 gene at different times during
      limb development indicate that the Hoxd genes have separable early and late roles
      in limb morphogenesis. In their early role, the Hoxd genes are involved in
      regulating the growth of the undifferentiated limb mesenchyme. Restriction of the
      expression of successive 5' Hoxd genes to progressively more posterior regions of
      the bud results in the asymmetric outgrowth of the limb mesenchyme. Later in limb
      development, Hoxd genes also regulate the maturation of the nascent skeletal
      elements. The degree of overlap in function between different Hoxd genes may be
      different in these early and late roles. The combined action of many Hox genes on
      distinct developmental processes contribute to pattern asymmetry along the A-P
      axis.

PMID- 7579520
TI  - The evolution of arthropod segmentation: insights from comparisons of gene
      expression patterns.
AB  - The comparison of gene expression patterns in a number of insect and crustacean
      species has led to some insight into the evolution of arthropod patterning
      mechanisms. These studies have revealed the fundamental nature of the parasegment
      in a number of organisms, shown that segments can be generated sequentially at
      the molecular level, and suggested that pair-rule pre-patterning might not be
      shared by all insects.

PMID- 7579521
TI  - The evolving role of Hox genes in arthropods.
AB  - Comparisons between Hox genes in different arthropods suggest that the diversity
      of Antennapedia-class homeotic genes present in modern insects had already arisen
      before the divergence of insects and crustaceans, probably during the Cambrian.
      Hox gene duplications are therefore unlikely to have occurred concomitantly with
      trunk segment diversification in the lineage leading to insects. Available data
      suggest that domains of homeotic gene expression are also generally conserved
      among insects, but changes in Hox gene regulation may have played a significant
      role in segment diversification. Differences that have been documented alter
      specific aspects of Hox gene regulation within segments and correlate with
      alterations in segment morphology rather than overt homeotic transformations. The
      Drosophila Hox cluster contains several homeobox genes that are not homeotic
      genes--bicoid, fushi-tarazu and zen. the role of these genes during early
      development has been studied in some detail. It appears to be without parallel
      among the vertebrate Hox genes. No well conserved homologues of these genes have
      been found in other taxa, suggesting that they are evolving faster than the
      homeotic genes. Relatively divergent Antp-class genes isolated from other insects
      are probably homologues of fushi-tarazu, but these are almost unrecognisable
      outside of their homeodomains, and have accumulated approximately 10 times as
      many changes in their homeodomains as have homeotic genes in the same
      comparisons. They show conserved patterns of expression in the nervous system,
      but not during early development.

PMID- 7579522
TI  - Protein families in the metazoan genome.
AB  - The evolution of development involves the development of new proteins. Estimates
      based on the initial results of the genome projects, and on the data banks of
      protein sequences and structures, suggest that the large majority of proteins
      come from no more than one thousand families. Members of a family are descended
      from a common ancestor. Protein families evolve by gene duplication and mutation.
      Mutations change the conformation of the peripheral regions of proteins; i.e. the
      regions that are involved, at least in part, in their function. If mutations
      proceed until only 20% of the residues in related proteins are identical, it is
      common for the conformational changes to affect half the structure. Most of the
      proteins involved in the interactions of cells, and in their assembly to form
      multicellular organisms, are mosaic proteins. These are large and have a modular
      structure, in that they are built of sets of homologous domains that are drawn
      from a relatively small number of protein families. Patthy's model for the
      evolution of mosaic proteins describes how they arose through the insertion of
      introns into genes, gene duplications and intronic recombination. The rates of
      progress in the genome sequencing projects, and in protein structure analyses,
      means that in a few years we will have a fairly complete outline description of
      the molecules responsible for the structure and function of organisms at several
      different levels of developmental complexity. This should make a major
      contribution to our understanding of the evolution of development.

PMID- 7579523
TI  - The hedgehog gene family in Drosophila and vertebrate development.
AB  - The segment polarity gene hedgehog plays a central role in cell patterning during
      embryonic and post-embryonic development of the dipteran, Drosophila
      melanogaster. Recent studies have identified a family of hedgehog related genes
      in vertebrates; one of these, Sonic hedgehog is implicated in positional
      signalling processes that show interesting similarities with those controlled by
      its Drosophila homologue.

PMID- 7579524
TI  - Growth factors in development: the role of TGF-beta related polypeptide
      signalling molecules in embryogenesis.
AB  - Embryonic induction, the process by which signals from one cell population
      influence the fate of another, plays an essential role in the development of all
      organisms so far studied. In many cases, the signalling molecules belong to large
      families of highly conserved proteins, originally identified as mammalian growth
      factors. The largest known family is related to Transforming Growth Factor-beta
      (TGF-beta) and currently consists of at least 24 different members. Genetic
      studies in Drosophila on the TGF-beta related gene, decapentaplegic (dpp), reveal
      the existence of conserved mechanisms regulating both the expression of the
      protein during development and the way in which it interacts with other
      signalling molecules to generate pattern within embryonic tissues. Comparative
      studies on another TGF-beta related gene, known as Bone Morphogenetic Protein-4
      (BMP-4), in Xenopus and mouse point to a conserved role in specifying
      posteroventral mesoderm during gastrulation. Analysis of other polypeptide
      signalling molecules during gastrulation suggests that their interaction in the
      generation of the overall body plan has also been conserved during vertebrate
      evolution.

PMID- 7579526
TI  - The evolutionary origin of development: cycles, patterning, privilege and
      continuity.
AB  - A scenario for the evolution of a simple spherical multicellular organism from a
      single eukaryotic cell is proposed. Its evolution is based on environmentally
      induced alterations in the cell cycle, which then, by the Baldwin effect, become
      autonomous. Further patterning of this primitive organism--a Blastaea, could
      again involve environmentally induced signals like contact with the substratum,
      which could then become autonomous, by, perhaps, cytoplasmic localization and
      asymmetric cell division. Generating differences between cells based on
      positional information is probably very primitive, and is well conserved; its
      relation to asymmetric cell division is still unclear. Differentiation of new
      cell types can arise from non equivalence and gene duplication. Periodicity also
      evolved very early on. The origin of gastrulation may be related to mechanisms of
      feeding. The embryo may be evolutionarily privileged and this may facilitate the
      evolution of novel forms. Larvae are secondarily derived and direct development
      is the primitive condition as required by the continuity principle.

PMID- 7579525
TI  - A class act: conservation of homeodomain protein functions.
AB  - Dramatic successes in identifying vertebrate homeobox genes closely related to
      their insect relatives have led to the recognition of classes within the
      homeodomain superfamily. To what extent are the homeodomain protein classes
      dedicated to specific functions during development? Although information on
      vertebrate gene functions is limited, existing evidence from mice and nematodes
      clearly supports conservation of function for the Hox genes. Less compelling, but
      still remarkable, is the conservation of other homeobox gene classes and of
      regulators of homeotic gene expression and function. It is too soon to say
      whether the cases of conservation are unique and exceptional, or the beginning of
      a profoundly unified view of gene regulation in animal development. In any case,
      new questions are raised by the data: how can the differences between mammals and
      insects be compatible with conservation of homeobox gene function? Did the
      evolution of animal form involve a proliferation of new homeodomain proteins, new
      modes of regulation of existing gene types, or new relationships with target
      genes, or is evolutionary change largely the province of other classes of genes?
      In this review, we summarize what is known about conservation of homeobox gene
      function.

PMID- 7579528
TI  - The evolution of echinoderm development is driven by several distinct factors.
AB  - We analyzed a comparative data base of gene expression, cell fate specification,
      and morphogenetic movements from several echinoderms to determine why
      developmental processes do and do not evolve. Mapping this comparative data onto
      explicit phylogenetic frameworks revealed three distinct evolutionary patterns.
      First, some evolutionary differences in development correlate well with larval
      ecology but not with adult morphology. These associations are probably not
      coincidental because similar developmental changes accompany similar ecological
      transformations on separate occasions. This suggests that larval ecology has been
      a potent influence on the evolution of early development in echinoderms. Second,
      a few changes in early development correlate with transformations in adult
      morphology. Because most such changes have occurred only once, however, it is
      difficult to distinguish chance associations from causal relationships. And
      third, some changes in development have no apparent phenotypic consequences and
      do not correlate with obvious features of either life history or morphology. This
      suggests that some evolutionary changes in development may evolve in a neutral or
      nearly neutral mode. Importantly, these hypotheses make specific predictions that
      can be tested with further comparative data and by experimental manipulations.
      Together, our phylogenetic analyses of comparative data suggest that at least
      three distinct evolutionary mechanisms have shaped early development in
      echinoderms.

PMID- 7579527
TI  - The evolution of cell lineage in nematodes.
AB  - The invariant development of free-living nematodes combined with the extensive
      knowledge of Caenorhabditis elegans developmental biology provides an
      experimental system for an analysis of the evolution of developmental mechanisms.
      We have collected a number of new nematode species from soil samples. Most are
      easily cultured and their development can be analyzed at the level of individual
      cells using techniques standard to Caenorhabditis. So far, we have focused on
      differences in the development of the vulva among species of the families
      Rhabditidae and Panagrolaimidae. Preceding vulval development, twelve Pn cells
      migrate into the ventral cord and divide to produce posterior daughters [Pn.p
      cells] whose fates vary in a position specific manner [from P1.p anterior to
      P12.p posterior]. In C. elegans hermaphrodites, P(3-8).p are tripotent and form
      an equivalence group. These cells can express either of two vulval fates (1
      degree or 2 degrees) in response to a signal from the anchor cell of the somatic
      gonad, or a nonvulval fate (3 degrees), resulting in a 3 degrees-3 degrees-2
      degrees-1 degree-2 degrees-3 degrees pattern of cell fates. Evolutionary
      differences in vulval development include the number of cells in the vulval
      equivalence group, the number of 1 degree cells, the number of progeny generated
      by each vulval precursor cell, and the position of VPCs before morphogenesis.
      Examples of three Rhabditidae genera have a posterior vulva in the position of P9
      P11 ectoblasts. In Cruznema tripartitum, P(5-7).p form the vulva as in
      Caenorhabditis, but they migrate posteriorly before dividing. Induction occurs
      after the gonad grows posteriorly to the position of P(5-7).p cells. In two other
      species, Mesorhabditis sp. PS 1179 and Teratorhabditis palmarum, we have found
      changes in induction and competence with respect to their presumably more C.
      elegans-like ancestor. In Mesorhabditis, P(5-7).p form the vulva after migrating
      to a posterior position. However, the gonad is not required to specify the
      pattern of cell fates 3 degrees-2 degrees-1 degree-2 degrees-3 degrees. Moreover,
      the Pn.p cells are not equivalent in their potentials to form the vulva. A
      regulatory constraint in this family thus forces the same set of precursors to
      generate the vulva, rather than more appropriately positioned Pn.p cells.

PMID- 7579529
TI  - Influence of puberty on lipids and lipoprotein profile in children with type 1
      diabetes mellitus.
AB  - In order to assess whether or not the lipoprotein profile worsens throughout
      puberty in children with type 1 diabetes mellitus and if this change is related
      to dietary compliance, we studied 46 (20 female, 26 male) children. At the
      beginning of the study, the mean age (+/- SD) was 10.9 +/- 1.1 years; all the
      children studied had reached a pubertal stage of P1, G1. The mean duration of
      diabetes (+/- SD) was 4.9 +/- 1.8 years. The diet and the lipoprotein profile of
      diabetic children were analysed at the beginning of the study and after 6 years.
      The quality of metabolic control of subjects studied had not changed
      significantly at the end of the study (haemoglobin HbA1c 7.6% +/- 2.1% vs 7.9% +/
      2.0%; NS). After puberty, the diabetic patients received more energy from
      carbohydrate and less from lipids. Total serum cholesterol and triglycerides and
      levels of low-density lipoproteins were significantly higher and of high-density
      lipoproteins lower in the diabetic patients after puberty than before (4.47 +/-
      0.7 mmol/l vs 5.99 +/- 0.6, P < 0.01; 0.90 +/- 0.02 mmol/l vs 1.45 +/- 0.03, P <
      0.01; 2.2 +/- 0.3 mmol/l vs 2.8 +/- 0.5, P < 0.01; 1.5 +/- 0.2 vs 1.1 +/- 0.2, P
      < 0.01, respectively). These results suggest a detrimental effect of puberty on
      lipoproteins; probably, dietary compliance plays a role in this worsening.
      Dietary education should be intensified during adolescence in order to present
      these changes.

PMID- 7579530
TI  - Anticoagulant protein C activity in non-insulin-dependent diabetic patients with
      normoalbuminuria and microalbuminuria.
AB  - Microalbuminuria in diabetic patients is associated with an increased
      cardiovascular risk which is not completely explained by an excess of
      conventional cardiovascular risk factors. A depression of physiologic inhibitors
      of blood coagulation could contribute to a thrombophilic state and to
      cardiovascular complications: data on protein C in diabetic patients are
      controversial, and no information exists about protein C activity in non-insulin
      dependent diabetic patients or its relation to the microalbuminuric state. The
      aim of this study was to assess protein C activity in non-insulin-dependent
      diabetic patients with and without microalbuminuria. Protein C activity was
      determined (Protein C Reagent, Boehringer Mannheim, Germany) in 29 non-insulin
      dependent diabetic patients with microalbuminuria (group A, > 20 micrograms/min),
      33 non-insulin-dependent diabetic patients with normoalbuminuria (group B), and
      in 36 non-diabetic healthy blood donors as a control group (group C). The groups
      were matched for sex, and no difference in age, body mass index, blood pressure,
      glycated haemoglobin or known duration of diabetes was observed between groups A
      and B. Protein C activity was similar in the three groups (mean +/- SD): group A,
      106.9% +/- 25.2%; group B, 109.3% +/- 27.6%; group C, 103.1% +/- 18.9%; F value
      0.58, NS. Protein C activity did not correlate significantly with body mass
      index, glycated haemoglobin, known duration of diabetes, age or albumin excretion
      rate in any of the groups or in the diabetic patients as a whole. No significant
      difference in protein C activity was observed in patients taking other therapy
      (diet, oral agents, insulin).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579531
TI  - Diastolic dysfunction is not related to changes in glycaemic control over 6
      months in type 2 (non-insulin-dependent) diabetes mellitus. A cross-sectional
      study.
AB  - Diastolic dysfunction may be the earliest marker of a diabetes-induced heart
      muscle disease which leads to the progressive development of cardiac failure.
      Left ventricular diastolic function was indirectly assessed using pulsed wave
      Doppler ultrasound mitral-flow velocities in 20 normotensive patients with a new
      diagnosis of type 2 diabetes mellitus, normal cardiac function and no evidence of
      coronary artery disease and in 16 age-matched normal subjects. Peak velocities of
      early (E) and late (A) left ventricular filling were measured. The median
      (interquartile ranges) peak E/A ratio was significantly reduced in the diabetic
      group 0.96 (0.8-1.2) vs 1.2 (1.1-1.3), P < 0.01. Despite improvements in
      glycaemic control over 3 months, HbA1c 9.9% (7.6%-10.5%) to 7.4% (6.5%-7.9%), P <
      0.001, maintained at 6 months, HbA1c 7.0% (6.4%-7.3%), there were no changes in
      the E/A ratio, 0.96 (0.83-1.15) and 0.95 (0.83-1.17), respectively. Furthermore,
      there was no correlation between percentage change in HbA1c and E/A ratio over 6
      months. The results of this study suggest that in patients with type 2 diabetes
      mellitus and normal systolic function, diastolic function was impaired at
      diagnosis and was not affected by an improvement in the glycaemic control.

PMID- 7579532
TI  - Diminished inhibitory effect of noradrenaline on insulin release from mouse
      islets transplanted to kidney.
AB  - Insulin release is inhibited by adrenergic alpha-2 agonism in normal beta-cells.
      To test whether the inhibitory response to noradrenaline is modified by
      transplantation, we studied insulin release from freshly isolated islets and from
      syngeneic islets transplanted under the kidney capsule of non-diabetic C57BL/6
      mice. When perifused in vitro, fresh islets, as well as grafts harvested 1 or 3
      weeks after transplantation, reacted to 2.5 mumol/l noradrenaline with a complete
      inhibition of insulin release induced by 16.7 mmol/l D-glucose. In contrast,
      islet grafts harvested after 6, 12, or 21 weeks exhibited a conspicuous insulin
      secretory response to 16.7 mmol/l glucose in the presence of 2.5 mumol/l
      noradrenaline. Also a concentration of 0.25 mumol/l, noradrenaline inhibited the
      glucose-induced insulin release from fresh islets but not from 6-week-old islet
      grafts. It is concluded that transplantation under the kidney capsule induces a
      decreased inhibitory responsiveness to noradrenaline in islet grafts.

PMID- 7579533
TI  - Frequency of Hashimoto's thyroiditis in children with type 1 diabetes mellitus.
AB  - A total of 1419 children with type 1 diabetes mellitus was investigated in order
      to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by
      microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases
      also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT
      were identified, a number significantly higher (P < 0.0001) than the distribution
      reported in the normal paediatric population. No typical antibody pattern was
      seen prior to the onset of HT, nor was an antibody threshold level found which
      could have been diagnostic for this disease. Patients with subclinical
      hypothyroidism were treated with L-thyroxine and were investigated regarding the
      behaviour of anti-thyroid autoantibodies; however, no significant changes were
      seen. The data showed a high frequency of HT in diabetic children, and therefore
      we recommend that children with type 1 diabetes mellitus should be screened for
      thyroid autoantibodies and those positive should undergo periodic thyroid
      function testing.

PMID- 7579534
TI  - Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced
      diabetes in naive and cyclosporin-treated low-responder murine strains.
AB  - We have previously shown that essential fatty acid (EFA) deficiency prevents
      diabetes and ameliorates insulitis in low-dose streptozotocin (LDS)-treated male
      CD-1 mice. The effects of EFA deficiency on the incidence of diabetes after LDS
      treatment has not been examined in other strains. In contrast to highly
      susceptible CD-1 mice, several other strains of mice are only partially
      susceptible to LDS treatment and do not develop appreciable insulitis; however,
      the susceptibility of these strains can be markedly increased by cyclosporin A
      (CsA) pretreatment to reduce suppressor cell function. Weanling male BALB/cByJ,
      DBA/2J, and C57BL/6J mice were placed on EFA-deficient (EFAD) or control diets
      for 2 months and then divided into experimental and control groups. Ten EFAD and
      10 control mice from each strain received LDS treatment (40 mg/kg/d 5 d); an
      additional 10 EFAD BALB/cByJ and another 10 control BALB/cByJ mice received
      subcutaneous CsA injections (20 mg/kg/d) for 14 days prior to and for 5 days
      simultaneous with LDS treatment (40 mg/kg/d 5 d). Plasma glucose levels for all
      mice were determined 3 times per week for 3 weeks after LDS treatment. Mean
      plasma glucose levels (+/- SEM) at the end of the experiment were significantly
      lower in the EFAD groups vs control groups in BALB/cByJ (P < 0.001), DBA/2J (P <
      0.00001), and C57BL/6J (P = 0.012) mice. CsA supplementation increased the
      severity of diabetes in LDS-treated BALB/cByJ mice (P < 0.0005); however, EFA
      deficiency also prevented diabetes in CsA-supplemented BALB/cByJ mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579535
TI  - Effect of recombinant human growth hormone treatment on insulin-like growth
      factor (IGF-I) levels in insulin-dependent diabetic patients.
AB  - Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth
      factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and
      4 healthy subjects. Diabetic patients were divided according to glucagon test
      result into CpN (10 patients without residual beta cell activity) and CpP (9
      patients with preserved beta-cell activity) and CpP (9 patients with preserved
      beta-cell activity) groups, and according to age into three groups (A = 21-30
      years; B = 31-40 years; C = 41-50 years). All control subjects belonged to group
      B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I
      every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given
      subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was
      evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with
      rhGH treatment was variable and insignificant in comparison with basal value
      without age-related differences in CpN diabetics. Progressively larger, age
      related increases in IGF-I concentrations were observed in CpP diabetic patients.
      This study indicates impairment of hepatic IGF-I generation capacity in diabetic
      patients without residual beta-cell activity and the importance of simultaneous
      actions of portal insulin and GH on hepatic IGF-I production.

PMID- 7579536
TI  - Humoral immune response to bovine serum albumin in new onset and established
      insulin-dependent diabetes mellitus.

PMID- 7579537
TI  - Insulin inhibits its own secretion from isolated, perifused human pancreatic
      islets.
AB  - It is still a controversial question whether insulin suppresses its own
      secretion. We prepared pure human islets from three pancreases by collagenase
      digestion and density gradient purification. Aliquots of 200 islet equivalents
      (IE, 150-microns sized-islets) were sequentially perifused at 37 degrees C with
      3.3 mmol/l glucose (3.3G, 40 min), 16.7 mmol/l glucose (16.7G, 30 min) and again
      3.3G (30 min) after 24 h, 37 degrees C culture in CMRL 1066 medium with or
      without the addition of either 200 or 400 microU/ml human insulin in the
      incubation medium (6 replicates each). Insulin secretion was assessed by C
      peptide (Cp) measurement in the perifusate. Without added insulin (C) and with
      200 (Ins200) or 400 (Ins400) microU/ml added insulin, basal Cp release was 0.12
      +/- 0.03, 0.14 +/- 0.02 and 0.14 +/- 0.04 ng/ml, respectively. At 16.7G, the
      first-phase secretion peak (expressed as Cp value) was significantly lower with
      Ins200 (0.47 +/- 0.13 ng/ml, P < 0.02) and Ins400 (0.68 +/- 0.15 ng/ml, P < 0.05)
      than C (0.83 +/- 0.15 ng/ml). The second-phase secretion peak was also
      significantly (P < 0.05) reduced with added insulin (Ins200: 0.47 +/- 0.08 ng/ml;
      Ins400: 0.45 +/- 0.07 ng/ml) than in its absence (C: 0.65 +/- 0.09 ng/ml).
      Accordingly, total Cp secretion was lower with Ins200 (10.6 +/- 2.3 ng/ml, P =
      0.03) and Ins400 (11.8 +/- 2.3 ng/ml) than with C (16.0 +/- 2.2 ng/ml).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579538
TI  - Dermatoglyphics in insulin-dependent diabetic patients with limited joint
      mobility.
AB  - Hand and palm dermatoglyphics were studied in 158 insulin-dependent diabetic
      children and adolescents [85 with limited joint mobility (LJM) and 73 without].
      The findings in this group were compared with those in 400 control subjects, with
      a similar racial distribution. The main dermatoglyphics alterations found in
      diabetic patients with LJM, as compared with non-LJM diabetic patients and
      controls, may be summarized as follows: (a) decrease in digital total ridges
      count (TRC); (b) higher frequency in the number of arches; (c) decrease in the
      sum of a line and cubital loops, particularly in the women; (d) increase in the
      number of t'-axial triradii. These alterations suggest a genetic aetiology of
      this complication. Further studies are recommended in order to provide more
      insight into the origin of this disorder.

PMID- 7579539
TI  - Alpha 2-adrenergic stimulation counteracts glucose-induced rise of sodium in
      pancreatic islets exposed to ouabain.
AB  - The effects of alpha 2-adrenergic activation by clonidine on sodium handling were
      analysed in beta-cell-rich pancreatic mouse islets. In the steady-state
      situation, clonidine (1 microM) amplified lowering of sodium induced by 20 mM
      glucose, while the content remained unchanged in 3mM glucose. The loss of sodium
      in Na(+)-deficient medium was stimulated by glucose but was not affected by
      clonidine. This agonist also did not influence the ouabain-induced uptake of
      sodium at 3 mM glucose but partially counteracted additional uptake in response
      to 20 mM glucose. Although lacking effects of its own, 5 microM yohimbine
      completely counteracted the action of clonidine. The glucose amplification of the
      ouabain-induced uptake of sodium was suppressed also by 10 microM of the Ca(2+)
      channel blockers methoxyverapamil and diltiazem. Both tolbutamide (100 microM)
      and dibutyryl cyclic AMP (1 mM) mimicked the action of glucose by promoting
      clonidine-sensitive uptake of sodium in the presence of ouabain. It is concluded
      that activation of alpha 2-adrenoceptors has profound effects on the sodium
      handling of pancreatic beta-cells exposed to glucose and other stimulators of
      insulin release.

PMID- 7579540
TI  - Relationship between insulin responses to D-glucose and to L-arginine in women
      with a history of gestational diabetes.
AB  - The relationship between insulin responses to glucose and to arginine was studied
      in non-obese women with previous gestational diabetes (PGD). One group, n = 10,
      had normal glucose tolerance (NGT) by WHO criteria and another, n = 8, had
      impaired glucose tolerance (IGT). A third group of women without PGD, n = 12, was
      also studied. A hyperglycaemic clamp (blood glucose level 11 mM) and an arginine
      stimulation test (150 mg/kg L-arginine followed by 10 mg/kg.min) were performed
      on separate days. The ratios of arginine to glucose responses 0-10 min differed:
      they were 1.00 for non-PGD, 1.29 for NGT and 1.46 for IGT (P < 0.02 vs non-PGD).
      A further difference between groups was the ratio between first- and second-phase
      glucose-induced insulin secretion, which was significantly decreased in IGT,
      0.72, compared with NGT, 0.98 (P < 0.01), and non-PGD, 1.05 (P < 0.005). However,
      within each group insulin responses 0-10 min to glucose and arginine were
      strongly correlated: for NGT (r = 0.75, P < 0.05), for IGT (r = 0.85, P < 0.01)
      and for women without PGD (r = 0.69, P < 0.05). Insulin sensitivity, as assessed
      by the M/I ratio, was non-significantly decreased in IGT (0.18 +/- 0.03 mg/kg.min
      per mU/l vs 0.26 +/- 0.03 in NGT and 0.28 +/- 0.03 in non-PGD, P < 0.1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579541
TI  - Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent
      diabetes: is Psammomys obesus a suitable animal model?
AB  - Recent data suggest that in a proportion of NIDDM patients there is a slowly
      evolving insulitis which results in a latent autoimmune diabetes leading to full
      insulin-dependence. Many animal models exist of NIDDM but none have reported the
      spontaneous existence of a similar phenomenon. We have re-examined the histology
      of pancreata from a few Psammomys obesus who had become insulin-dependent in the
      late stages of NIDDM. We report here the unexpected finding of the presence of
      insulitis in these animals and suggest that they could be a model for the
      clinical observation of latent IDDM in NIDDM patients.

PMID- 7579542
TI  - Neonatal rat islets of Langerhans and fetal rat pancreas. Isolation,
      immunohistochemical, functional, and autoradiographic evaluation.
AB  - The aim of this study was to develop an optimal isolation technique for neonatal
      rat islets of Langerhans, to perform functional evaluation in vitro, to evaluate
      immunohistochemically isolated rat islets and fetal rat pancreata after a
      variable period of culture, and to study growth potentials by means of
      autoradiography. The islets were isolated using minor modifications of standard
      procedures including collagenase and DNase. Islets were separated on a
      discontinuous Percoll gradient. The maximum yield of islets amounted to 240 per
      pancreas. Fetal pancreata from rats were cultured under similar conditions as
      neonatal islets to compare their insulin secretory capacity after different
      periods of culture. The insulin secretion increased gradually, and isolated
      islets achieved a similar secretion potential to adult rat islets. The mitotic
      activity of both islets and fetal pancreata was confirmed using tritiated
      thymidine. The isolation procedure was found suitable for producing well
      functioning islets, which could be kept in culture for a period of about 1 month
      without deterioration in their insulin secretory capacity. The gradual increase
      in insulin secretory capacity of islets and fetal pancreata was due, in part, to
      hyperplasia and not just hypertrophia. Autoradiographical evaluation revealed a
      high mitotic activity after culture, in particular of fetal pancreata. Fetal
      pancreata cultured for about 10 days showed a phenomenon of budding endocrine
      cells at the organ surface. A high mitotic activity was found in these buds.

PMID- 7579543
TI  - Understanding the new era in health care accountability: report cards.
AB  - In this period of revolutionary change, it is important for all health care
      professionals to understand the dramatic shift that is taking place in assessing
      and evaluating the quality of health care services using report cards. The
      article provides a brief historical perspective of the report card and quality
      outcome measurement activities. Furthermore, it provides an example of the
      quality improvement process utilized in improving patient care services in
      nursing units in recent years. The process relies on establishing specific
      standards of performance and communicating the impact of the standards on patient
      satisfaction using report cards.

PMID- 7579544
TI  - The nursing minimum data set, standardized language, and health care quality.
AB  - Providers and consumers of health care have been attempting to define quality for
      the past several decades. The article describes one of nursing's contributions to
      the multidisciplinary health care quality revolution: its ability to provide a
      more complete and holistic picture of the consumer (patients/clients). Nursing's
      focus on responses to health care problems, not just illness events in isolation,
      provides insight into causes and effective management strategies for health
      problems. The Nursing Minimum Data Set (NMDS) documents patient/client responses,
      interventions, patient-sensitive outcomes, and resource consumption. By
      implementing the NMDS, nursing collaborates with other health care professionals
      to identify the needs of patient populations as well as the needs of individual
      patients. The article examines the relationship of the NMDS to other health care
      databases used in quality measurement, describes the integral role of
      standardized language in implementing the NMDS, provides examples of NMDS data
      analyses to address specific aspects of quality measurement, and outlines a
      methodology for using nonstandardized data.

PMID- 7579545
TI  - Using external data and databases: issues and sources.
AB  - Third party payers, employers, and accrediting organizations such as the Joint
      Commission for Accreditation of Healthcare Organization have played an important
      role in moving health care organizations toward the use of outcomes to measure
      quality. In addition, other external forces, such as shrinking health care
      resources and an increasingly competitive health care environment, have pressured
      organizations to implement continuous quality improvement (CQI) programs. These
      programs are an important component in effective and efficient organizational
      operations. Health care organizations must provide the best quality at the lowest
      cost to survive today. CQI programs incorporate internal and external comparisons
      to demonstrate improvement. Internal and external comparisons are important to
      validate the organization's level of quality. The article concentrates on the use
      of external comparisons, sources of external data or databases, and issues
      involved in external comparisons or benchmarking.

PMID- 7579546
TI  - Readiness of nurses for electronic networking for quality assessment and
      improvement.
AB  - Quality assessment and improvement (QAI) is a rapidly evolving component of
      health care. Its operationalization in clinical practice can be greatly enhanced
      by information sharing, best practice networking, and communication of
      experiences and resources. Nurses play a key role in both QAI and information
      sharing in this endeavor. Electronic communication supports the rapid sharing of
      QAI-related information across agencies to link nurses with a common interest in
      continuously improving the quality of health care delivery. It offers the
      opportunity to diminish the barrier of distance, which is especially relevant for
      nurses in rural areas. Before electronic communication was established as an
      information-sharing mechanism, however, the readiness of nurses in both rural and
      urban/suburban settings was assessed. A convenience sample of nurses in western
      New York, who were surveyed via written questionnaire regarding electronic
      communication, most often described their comfort in using this medium as
      uncertain. This finding supports the need for preliminary preparation focusing
      upon the skills and experience needed to utilize the computer as a communication
      medium.

PMID- 7579547
TI  - Health insurance status and ill health: implications for health professionals.
AB  - The article examines the relationship between health insurance status and the
      instances of self-reported ill health among 1,235 Nebraska adults. Ill health
      conditions include episodes of both acute and chronic conditions. Health status
      is measured as Medicare, Medicaid, private health insurance, veterans' benefits,
      and uninsured. Both Medicare and Medicaid are related to frequency of reported
      episodes of ill health, but only Medicare is related to reports of chronic
      conditions. Health professionals interested in improving and sustaining
      acceptable quality of health care should focus attention on the Medicare and
      Medicaid populations and not be concerned that adding the currently uninsured to
      the privately or publicly insured populations would, in the aggregate, increase
      their burdens of providing care. The study demonstrates the value of using
      population-based survey data to help health professionals anticipate and respond
      to patient demand.

PMID- 7579549
TI  - Outcomes: the mainstay of a framework for quality care.
AB  - To move toward quality care, it is important to understand all relevant
      terminologies and concepts. A conceptual framework is useful for organizing all
      the relevant practice components, such as professional standards, protocols,
      critical paths, and care plans. The article presents a framework for quality care
      that focuses on outcomes and defines and incorporates all the other essential
      elements that are used to reflect quality.

PMID- 7579548
TI  - New routes in pediatric sedation: a research-based protocol for intranasal
      midazolam.
AB  - The quality assurance and improvement committee on a general pediatric unit
      identified a problem with sedation for neuroradiologic studies. Twenty-three
      percent of children (n = 63) failed to sedate with one dose of chloral hydrate,
      resulting in delays or cancellations. For children receiving a second dose of
      chloral hydrate, average time to study completion was 97 minutes, and 70 percent
      of the children (n = 10) were successfully sedated. A protocol was developed for
      the use of intranasal midazolam as the follow-up agent. Evaluation on a pilot
      unit revealed that the average time to test completion decreased to 55 minutes
      and that the success rate was 82 percent (n = 11). The nursing staff prefer the
      use of intranasal midazolam as the follow-up agent because of its quicker
      sedation and decreased duration of action.

PMID- 7579550
TI  - Evaluating a nursing care delivery model using a quality improvement design.
AB  - The goal to develop and implement a new model of nursing care delivery grew out
      of administrative and shared governance initiatives to improve the quality of
      nursing care. This evaluative study used both quantitative and qualitative
      methods. Seven principles related to quality were identified and became the
      driving force behind the changes. Aspects of these changes in care delivery were
      piloted on a neurological unit and included implementation of collaborative
      rounds, a modular structure, role changes, and work redesign. Frequency
      distribution, questionnaire, focus group, and financial data indicated that there
      had been improvement in the delivery of care in addition to financial benefits. A
      considerable amount of the data provided evidence that supported continuing the
      changes.

PMID- 7579551
TI  - The nursing minimum data set: use in the quality process.
AB  - There is an increased need to use nursing information systems that include
      elements of the Nursing Minimum Data Set (NMDS). The NMDS is a framework within
      which to collect and retrieve data that are essential to the quality process,
      including structure, process, and outcome components. In using the NMDS for
      quality evaluation, there are several issues to be addressed, including database
      development, standardized language for nursing, standard and guideline
      development, and data quality. Nurses need to have standardized, computerized,
      essential nursing data to evaluate effectiveness of care and to demonstrate the
      contributions they make to client outcomes.

PMID- 7579552
TI  - Combination chemotherapy for disseminated malignant melanoma.
AB  - Malignant melanoma, once disseminated, is associated with very short survival
      times and has proven highly resistant to systemic therapy. Although many
      chemotherapeutic agents can produce small response rates in these patients, the
      most consistent responses occur with dacarbazine (DTIC). Numerous combination
      regimens, with and without DTIC, have been tested against disseminated melanoma,
      with varying and inconsistent outcomes. The most encouraging results have
      occurred with the combination of DTIC, cisplatin, BCNU and tamoxifen. The use of
      high-dose chemotherapy with and without autologous bone marrow support and the
      addition of biologic agents such as inteferon-alpha and interleukin-2 to
      conventional chemotherapy have also been actively investigated. This paper
      reviews the various approaches taken against disseminated melanoma employing
      systemic chemotherapy.

PMID- 7579553
TI  - Possible mechanisms in the emergence of tamoxifen-resistant breast cancer.
AB  - Tamoxifen (TAM), a non-steroidal antiestrogen, is the endocrine treatment of
      choice for all stages of breast cancer. However, despite a favorable initial
      response to therapy, most tumors will eventually exhibit TAM resistance resulting
      in disease recurrence. Several mechanisms of TAM resistance have been proposed,
      yet a single distinct mechanism has not been identified. We will systematically
      consider the following steps of the estrogen receptor (ER)-mediated signal
      transduction pathway to identify possible sites of alteration leading to
      tamoxifen-resistance: (1) ligand metabolism and availability, (2) loss or
      mutation of the ER, (3) defects in ER post-translational modification, and (4)
      alteration of the estrogen response element (ERE). In particular, the ERE will be
      discussed as a position in the signal transduction pathway with considerable
      potential, if altered, to confer TAM resistance.

PMID- 7579554
TI  - Efficacy and tolerability of Casodex in patients with advanced prostate cancer.
      International Casodex Study Group.
AB  - The efficacy and tolerability of Casodex, a new non-steroidal antiandrogen, were
      studied in 267 patients with advanced prostate cancer. All patients received
      Casodex, 50 mg daily, as monotherapy. The objective response rate was 55.5% and
      the subjective response rate was 56.1%. The most common adverse events were the
      expected pharmacological effects of breast tenderness, gynecomastia and hot
      flushes. No other adverse events were reported in more than 5% of patients. There
      was minimal occurrence of impotence, loss of libido and diarrhea. The results
      show that Casodex 50 mg is effective and well tolerated in the treatment of
      advanced prostate cancer.

PMID- 7579555
TI  - Tropisetron alone or in combination with dexamethasone for the prevention and
      treatment of emesis induced by non-cisplatin chemotherapy: a randomized trial.
AB  - This study compared the efficacy and tolerability of tropisetron (Navoban,
      Novaban) alone or in combination with dexamethasone for the treatment of emesis
      induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126
      patients with cancer, who had never received chemotherapy and who required at
      least two courses of moderately emetogenic non-cisplatin chemotherapy each
      lasting for a minimum of 5 days, were recruited into the study. Patients were
      randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg
      i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater
      control of acute and delayed vomiting and nausea was achieved in patients given
      the tropisetron-dexamethasone combination than in those who received the
      tropisetron-placebo treatment. The majority of adverse events were mild and could
      be attributed to the chemotherapeutic regimen used or to the underlying disease.
      Patients and investigators both rated tropisetron alone or in combination with
      dexamethasone as a highly effective and well-tolerated antiemetic treatment. The
      results of this study show that tropisetron, 5 mg o.d., is an effective, well
      tolerated and simple to use antiemetic treatment for patients receiving
      moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone
      increases the efficacy of tropisetron without significantly decreasing its
      tolerability.

PMID- 7579556
TI  - Development of a propidium iodide fluorescence assay for proliferation and
      cytotoxicity assays.
AB  - A propidium iodide fluorescence assay (PIA) was developed to characterize the in
      vitro growth of human tumor cell lines as well as to test the cytotoxic activity
      of standard compounds. Propidium iodide (PI) was used as a dye which penetrates
      only damaged cellular membranes. Intercalation complexes are formed by PI with
      double-stranded DNA which effect an amplification of the fluorescence. Incubation
      of the total cell population with PI and subsequent fluorescence detection
      allowed assessment of the number of non-vital cells (first measurement). After
      freezing the cells at -20 degrees C for 24 h PI had access to total DNA leading
      to total cell population counts (second measurement). The number of viable cells
      was calculated by the difference between these two measurements. In the
      proliferation and cytotoxicity assays 5 x 10(3) cells per well were plated in 96
      multiwells and finally stained with 50 micrograms/ml PI in 25 microliters for 10
      min. A correlation between the log of cell number and the log of fluorescence
      units could be demonstrated over a 2.5-3 log range (r = 0.97). The lower limit of
      cell detection was 150-500 cells/wells. In cytotoxicity assays eight clinically
      used cytostatics were tested which effected a clear dose-response relationship (r
      = 0.93-0.98) and high reproducibility (r = 0.92). In conclusion, this assay is a
      simple and rapid test system, the main advantages are the absence of any washing
      steps and the small number of tumor cells necessary for drug testing. The PIA can
      easily be used for cell number determinations in biological and pharmacological
      studies.

PMID- 7579557
TI  - Simultaneous combination of microtubule depolymerizing and stabilizing agents
      acts at low doses.
AB  - The combined activity of a stabilizing and a depolymerizing agent was studied on
      microtubule formation in vitro and on cellular parameters related to the
      cytoskeleton. New compounds in each class of microtubular drugs, docetaxel, as
      stabilizing agent, and CI 980, as colchicine analog, currently in clinical
      trials, were tested at high and low concentrations. Simultaneous combination of
      docetaxel and CI 980, both in vitro and in cell lines, induced microtubule
      structures resulting from the association of the effects of the two drugs: short
      and numerous microtubules in vitro, abnormal asters or short bundles in cells
      depolymerized in their periphery. Moreover, combining the two drugs at low
      concentrations inducing neither modification of the microtubular network nor
      variation in cell polymerized tubulin content showed synergistic effects in
      mitotic cell block and, at lower concentrations, in inhibition of proliferation
      in the KB 3-1 cell line. Similar qualitative results were obtained with
      paclitaxel and colcemid, used in the place of docetaxel and CI 980, respectively.
      At low doses, the taxoid/colchine analog combination seems to induce some degree
      of mitotic inhibition, resulting from a subtle effect on the inhibition of
      microtubule dynamics.

PMID- 7579558
TI  - Relationship of mitochondrial function and cellular adenosine triphosphate levels
      to pMC540 and merodantoin cytotoxicity in MCF-7 human breast cancer cells.
AB  - In previous studies we have reported that preactivated merocyanine 540 (pMC540)
      and its chemically synthesized isolates merocil and merodantoin mediate their
      preferential cytotoxicity towards certain types of malignant cells including
      human breast cancer cells in vitro and in vivo. The mechanism of cytotoxic action
      appears to be, in part, via initial interaction with topoisomerase II leading to
      apoptosis. To further build upon these findings we now show that pMC540 and
      merodantoin disrupt mitochondrial morphology and function in intact MCF-7 human
      breast cancer cells as seen by their causing the release of rhodamine 123 from
      prestained cells, a rapid reduction in ATP levels, inhibition of succinate
      dehydrogenase activity and oxygen consumption. These data suggest that
      mitochondria may also be an important target for the cytotoxic action of pMC540
      and merodantoin mediated through disruption of the energy balance.

PMID- 7579559
TI  - Inhibition of colon cancer cell proliferation by antisense oligonucleotides
      targeting the messenger RNA of the Ki-ras gene.
AB  - Point mutations that activate the Ki-ras proto-oncogene are present in
      approximately 50% of human colorectal tumors and the activated Ki-ras gene is
      considered to play an important role in colorectal cancer cell proliferation.
      Five different colon cancer cell lines and two kinds of control cell lines were
      treated with antisense oligonucleotides complementary to the messenger RNA of Ki
      ras. Treatment with antisense oligonucleotides at concentrations between 10 and
      40 microM significantly and dose-dependently inhibited cell growth, colony
      formation and Ki-ras protein production of the colon cancer cells with activated
      Ki-ras, but did not affect the normal cells and colon cancer cells without Ki-ras
      mutation. These results show that use of synthetic oligonucleotides is an
      effective way of producing antisense-mediated changes in the behavior of human
      colon cancer cells with an activated Ki-ras gene.

PMID- 7579561
TI  - Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell
      cycle.
AB  - We investigated the effect of cyclosporin A (CsA) or FK506 on the cytotoxicity of
      anthracyclines against a human laryngeal cancer cell line, KB cells, and a multi
      drug resistance cell line, VJ-300 cells. CsA and FK506 enhanced the cytotoxicity
      of anthracyclines, especially in the VJ-300 cells. The intracellular
      concentrations of epirubicin (EPIR), daunomycin (DM), adriamycin (ADM) and THP
      adriamycin (THP) were increased by the addition of CsA or FK506 in VJ-300, but
      not in KB cells. The intracellular accumulation of EPIR was most increased when
      CsA or FK506 was concomitantly administered with the drug. We also asked whether
      CsA or FK506 might influence the cycle of KB or VJ-300 cells. The population of
      cells in each phase of the cell cycle was little changed in both KB and VJ-300
      cells when 0.3 microM ADM was administered for 24 h. Both CsA and FK506
      significantly increased the ADM-induced accumulation of VJ-300 cells in G2M
      phase, in comparison with findings with KB cells. Thus, the reversal of MDR by
      CsA or FK506 is related to increased intracellular concentrations of cytotoxic
      drugs and, as a result, the increased G2M accumulates in MDR cells. Among of
      antrhacyclines, EPIR was most effective when concomitantly combined with CsA or
      FK506 in VJ-300 cells.

PMID- 7579560
TI  - Inhibition of breast and ovarian carcinoma cell growth by 1,25-dihydroxyvitamin
      D3 combined with retinoic acid or dexamethasone.
AB  - This study examined the growth inhibitory effects of combining 1,25
      dihydroxyvitamin D3 (calcitriol) with retinoic acid or dexamethasone against
      cultured breast and ovarian carcinoma cells. Retinoic acid (12.5-50 nM) increased
      the effectiveness of calcitriol (12.5-50 nM) against MCF-7 and NIH:OVCAR3 cells,
      with synergistic interactions at two of the three ratios tested. Dexamethasone
      augmented calcitriol effects, with synergism at 0.05 and 0.1 nM dexamethasone in
      MCF-7 cells and 5 nM in Caov-4 ovarian cells. This study showed favorable
      interactions for calcitriol-retinoic acid and calcitriol-dexamethasone
      combinations in breast and ovarian cancer cell lines.

PMID- 7579562
TI  - Cytotoxic effect of calcein acetoxymethyl ester on human tumor cell lines: drug
      delivery by intracellular trapping.
AB  - Calcein acetoxymethyl ester (calcein/AM) and some related cellular dyes with a
      cytoplasmic distribution were investigated with respect to cellular hydrolysis,
      accumulation, efflux and cytotoxicity in a panel of established human cell lines,
      including multidrug resistant (MDR) phenotypes. At 0.1-1 micrograms/ml,
      calcein/AM was highly cytotoxic against several cell lines, even after short-term
      exposure (30 min). Calcein/AM induced no immediate loss (3 h) of membrane
      integrity and the drug was more active against low compared with high density
      plated cells. In cell lines with the MDR phenotype and in the renal carcinoma
      cell line ACHN, the drug was considerably less active. Non-esterified calcein had
      no effect and calcein/AM was significantly more potent than other structurally
      related fluorescein analogs and AM esters tested. Although MDR cell lines showed
      a decreased cellular hydrolysis and accumulation of the dye, there was no strict
      relationship between cytoplasmic calcein exposure and cytotoxic activity. The
      rate of efflux was low in the two most sensitive cell lines, the human lymphoma U
      937-GTB and its vincristine (vcr) resistant subline U-937/vcr10, while the
      remaining cell lines showed similar biphasic efflux patterns, including cell
      lines of the MDR phenotype. The results show that calcein/AM has cytotoxic
      activity against human tumor cell lines at low concentrations. The effect appears
      dependent on the intracellular trapping of the drug, although the specific
      cellular target remains unknown. Due to its cytotoxic efficacy and unique
      principle of cellular drug delivery, further investigation of calcein/AM and
      related compounds as potentially new anticancer agents seems warranted.

PMID- 7579563
TI  - Combination therapy with 5-fluorouracil and L-canavanine: in vitro and in vivo
      studies.
AB  - L-Canavanine (CAV) is a potent L-arginine antagonist, produced by legumes such as
      the jack bean, Canavalia ensiformis. CAV is cytotoxic to MIA PaCa-2 human
      pancreatic cancer cells. We sought to determine whether CAV's efficacy as an
      anticancer agent might be increased in combination with 5-fluorouracil (5-FU), a
      pyrimidine antimetabolite with activity against solid tumors. Using optimal
      conditions for the expression of CAV's cytotoxicity against MIA PaCa-2 cells, CAV
      was more cytotoxic to the cells than 5-FU. The combination of both drugs at a
      fixed molar ratio of 1:1 exhibited synergistic effects in the cells as determined
      by combination index analysis. The combination of 5-FU:CAV was tested at a ratio
      of 5:1 and exhibited antagonism at lower effect levels, additivity at 50% effect
      levels and slight synergism at higher effect levels. A 10:1 combination of both
      drugs (5-FU:CAV) exhibited antagonistic effects at all levels. When the drugs
      were combined at a molar ratio of 20:1, increased antagonism was observed. When
      CAV (1.0 or 2.0 g/kg daily) and/or 5-FU (35 mg/kg daily) was administered to
      colonic tumor-bearing rats for five consecutive days, the antitumor activity of
      the drug combination was significantly greater than the combined effects of
      either drug alone. However, the body weight loss experienced by CAV-treated rats
      was increased in those rats exposed to a combination of both drugs. These studies
      using different tumors provide in vitro and in vivo evidence that combination
      therapy offers a viable means of improving CAV's intrinsic efficacy while
      decreasing the concentration of 5-FU required to produce the same cytotoxic
      effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579564
TI  - Spontaneous fracture of implanted central venous catheters in cancer patients:
      report of two cases and retrospective analysis of the 'pinch-off sign' as a risk
      factor.
AB  - Spontaneous fracture of central venous catheters (CVC) has been reported. It
      results from repeated compression of the extravasal part of the CVC between the
      clavicle and the first rib. The so called pinch-off sign (POS) of the CVC as
      visible on a chest radiograph has been described as a warning for this
      complication. Fracture of CVC in patients receiving chemotherapy results in
      extravasation of the drug which may have serious consequences. We describe the
      spontaneous fracture of a CVC in two cancer patients. Subsequently we
      retrospectively analyzed chest radiographs for the POS of 77 cancer patients who
      received chemotherapy through a CVC and correlated these results with the
      occurence of complications related to CVC compression. In 77 patients a total of
      97 CVC were implanted for a median duration of 7 months. Four CVC (4%) showed a
      grade 2 POS (change in course of CVC)CVC with luminal narrowing) on a chest
      radiograph. In three of these (75%) a compression-related complication occurred
      versus no compression-related complications in 93 CVC showing a POS of grade 1
      (change in course of CVC without narrowing) or 0 (no change in course of CVC).
      The grade of POS on a chest radiograph may vary with the position of the patient,
      but all grade 2 POS were visible in the upright position. We recommend a chest
      radiograph in the upright position after placement of a CVC for grading of the
      POS. CVC showing a grade 2 POS should be removed or at least checked by a chest
      radiograph before the start of each chemotherapy infusion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7579565
TI  - 5-Fluorouracil, folinic acid and cisplatin in advanced colorectal cancer: a pilot
      study.
AB  - The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated
      activity in colorectal cancer (CC). Cisplatin is reported to have synergistic
      activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients
      who had previously received chemotherapy with FA + 5-FU and relapsed. Two months
      after the last dose of FA + 5-FU and documentation of relapse, patients continued
      with the regimen consisting of cisplatin 20 mg/m2 in 15 min i.v. infusion
      followed by FA 500 mg/m2 in 1 h i.v. infusion, in the middle of which 5-FU 500
      mg/m2 i.v. bolus was administered, with adequate post-hydration. This was
      repeated weekly for 4 weeks followed by a 2 week rest, for a maximum of six
      cycles. A total of 30 patients with CC that had relapsed to the combination of FA
      + 5-FU were treated; 23 had previous surgery and none had radiotherapy. Local
      recurrence was found in eight patients, metastases in the liver in 21, in lymph
      nodes in six, lung six and peritoneal metastases in seven. Seven patients
      responded partially. Toxicity requiring dose reduction or discontinuation of
      treatment included neutropenia 42% (grade 3:7%), mucositis 28% (grade 1:2),
      diarrhea 63% (Grade 3:10%), nausea-vomiting 55% (Grade 3:10%), increased
      creatinine value in three patients and peripheral neuropathy in two patients. We
      conclude that evaluation of this regimen shows substantial toxicity, with
      satisfactory response as a second line chemotherapy in these heavily pretreated
      patients.

PMID- 7579567
TI  - Escalating dose of tegafur combined with oral etoposide in metastatic gastric
      carcinoma.
AB  - Fifteen patients with advanced gastric cancer received orally etoposide 100 mg
      daily for 14 days and escalating doses of tegafur. The starting dose was 400 mg
      daily. The maximum tolerated dose of tegafur was identified at 850 mg daily.
      Unacceptable toxicity was seen at 1000 mg, and consisted of diarrhea, stomatitis
      and leukopenia. Two partial responses were seen at 800 mg daily. In conclusion,
      our data show that etoposide and tegafur can be safely administered in
      combination by the oral route.

PMID- 7579568
TI  - Camptothecin cytotoxic effects in vitro: dependency on exposure duration and
      dose.
AB  - A survey of in vitro cytotoxic effects of camptothecin in human epitheliod
      sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma
      (PNET) cell lines, was done. We chose the MTT assay to measure survival and
      observed that 24 h exposures to camptothecin caused consistently greater toxicity
      than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range.
      There was a 10-fold range of growth rates measured by OD after 5 days exposure
      and varied expression of MDR1 in these cell lines--none of which could be
      correlated with tumor sensitivity to drug. The most sensitive cell lines were
      colon and glioblastoma, and the most resistance were ovarian, breast and
      epithelioid sarcoma.

PMID- 7579566
TI  - Stability of ifosfamide in solutions for multiday infusion by external pump.
AB  - The stability of ifosfamide in Ringer lactate buffer solution either alone or
      mixed with mesna at 37 degrees C for a 7-day period was analyzed by HPLC. This
      study was performed to investigate the feasibility of continuous infusion of
      ifosfamide by a multiday pump in order to reduce the toxicity and to increase the
      production of active alkylating metabolites of the parent drug. The total decay
      of ifosfamide activity did not exceed 3.2% at day 7. We conclude that ifosfamide
      can be safely delivered in a 7-day infusion with no significant loss of activity.

PMID- 7579570
TI  - Molecular analysis of the Methoprene-tolerant gene region of Drosophila
      melanogaster.
AB  - Adult functions of juvenile hormone (JH) have been described for Drosophila
      melanogaster and other dipteran insects, but preadult function for this hormone
      remains largely unknown in this order of insects. We have identified a mutation
      of Drosophila, Methoprene-tolerant (Met), which appears to alter JH reception
      during late larval development. The molecular cloning of Met will be a step
      toward understanding this gene and possibly identifying a preadult role(s) for
      JH. Molecular cloning was initiated using the technique of transposon-tagging
      with a transposable P element. P-element insertional alleles of Met were
      generated, and genomic libraries were constructed from two of these alleles. From
      these libraries P-element-bearing clones were isolated that in situ hybridized to
      the cytogenetic region where Met had been previously localized by genetic
      methods. Two of the alleles were shown to have complete P-elements inserted in
      similar, but not identical, locations in the predicted cytogenetic region where
      Met is located. A late-larval cDNA library was screened to identify
      transcriptional units in this region, and clones were recovered with homology to
      a DNA fragment abutting the P-element insertion site. These clones may represent
      Met cDNA molecules.

PMID- 7579569
TI  - Cyclosporine A increases serum cortisol levels in rabbits.
AB  - P-glycoprotein (P-gp), a membrane protein that was originally found to be
      involved in the efflux of cytotoxic drugs out of the tumor cells, is also present
      in a variety of normal human and animal tissues, such as the adrenal cortex. The
      function of P-gp in the adrenal cortex has not been defined yet. The aim of our
      study was to determine whether the blockade of P-gp by cyclosporine A (CsA)
      dissolved in Cremophor EL (Crem) inhibits cortisol secretion in rabbits. In 14
      rabbits, the baseline and ACTH stimulated serum cortisol levels were measured
      before and after CsA treatment. Seven rabbits were treated with 2 x 30 mg/kg CsA
      and seven with 2 x 90 mg/kg CsA injected s.c. Serum cortisol levels were
      determined by radioimmunoassay adjusted for expected values. The whole blood CsA
      levels were determined by a commercially available fluorescence polarization
      immunoassay. Serum cortisol levels, both baseline and ACTH stimulated,
      significantly increased after both low and high dose CsA treatment. The increase
      was dose dependent. The mean baseline cortisol levels increased from 5.7 (SD =
      6.3) to 15.0 nmol/l (SD = 7.2) in the low dose group and from 7.7 (SD = 4.9) to
      44.9 nmol/l (SD = 13.8) in the high dose group. The mean cortisol levels 8 h
      after ACTH stimulation increased from 53.3 (SD = 34.5) to 106.0 nmol/l (SD =
      33.0) in the low dose group and from 47.7 (SD = 12.2) to 153.0 nmol/l (SD = 55.1)
      in the high dose group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579571
TI  - Corpora allata of the larval tobacco hornworm contain a calcium/calmodulin
      sensitive adenylyl cyclase.
AB  - An assay was developed with which to study basic characteristics of an adenylyl
      cyclase in the corpora allata (CA) of the tobacco hornworm, Manduca sexta. The
      assay used glands collected and frozen at -80 degrees C, to circumvent the
      problem of tissue availability. With this protocol for storage of tissue, less
      than 25% of the enzyme activity in fresh tissue was lost. Substances such as
      sodium fluoride (NaF) and Gpp(NH)p (a non-hydrolyzable GTP analog), which
      typically stimulate the adenylyl cyclases in other insect tissues, increased
      enzyme activity several-fold. There was a progressive decrease in the capacity of
      the CA adenylyl cyclase to be stimulated by NaF during the fifth stadium,
      suggesting a possible developmental change in the capacity of the associated G
      protein to be stimulated by NaF. The calcium/calmodulin (CaM) dependence of
      adenylyl cyclase activity was also investigated. The results demonstrated that
      addition of up to 10(-4) M calcium to assays of enzyme activity in whole gland
      homogenates of both larval (day 0) and prepupal (day 6) CA resulted in only a
      slight increase in the activity of the enzyme over basal rates in the presence of
      the calcium chelator EGTA. However, addition of as little as 5 microM CaM in the
      presence of 10(-4) to 10(-3) M calcium increased adenylyl cyclase activity three
      to five-fold. A similar stimulation was obtained with washed membrane
      preparations of day 0 and day 6 glands, but required a substantially higher
      concentration of CaM. Results demonstrated that the CA possess a calcium/CaM
      dependent adenylyl cyclase from day 0 through day 6.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579574
TI  - Comparison of ecdysteroid production in Drosophila and Manduca: pharmacology and
      cross-species neural reactivity.
AB  - In both Manduca sexta and Drosophila melanogaster, metamorphic events are driven
      by ecdysteroids whose production in prothoracic gland (PGs) is stimulated
      periodically by neural factors. Differences in the life cycle of moths and flies
      have made it difficult to compare the regulation of ecdysteroid biosynthesis in
      these two species. As in Manduca, at least two neural factors in the larval
      Drosophila BVG complex were separable by molecular weight, and they stimulated
      increased ecdysteroid biosynthesis from the ring gland, a composite organ that
      includes PG cells. Drosophila neural extracts accelerated ecdysteroid
      biosynthesis in Manduca PGs and, conversely, partially purified Manduca PTTH
      preparations elevated ecdysteroid biosynthesis in Drosophila ring glands,
      suggesting that the two species may share structurally similar prothoracicotropic
      factors. Drosophila ring glands required the presence of calcium ions to respond
      to neural extracts, but the phosphodiesterase inhibitor MIX and cAMP analogues
      exerted little, if any, positive effect on production. Mean ecdysteroid
      production rates of BVG-ring gland complexes taken from Drosophila larvae during
      various phases of the wandering period were often submaximal and highly variable,
      suggesting that they fluctuate widely prior to pupariation. Based on available
      data in Drosophila and the Manduca model for the control of ecdysteroid
      biosynthesis, a developmental scheme for neuroendocrine control in Drosophila is
      proposed.

PMID- 7579573
TI  - Pathway and regulation of JHIII-Bisepoxide biosynthesis in adult Drosophila
      melanogaster corpus allatum.
AB  - Adult female Drosophila melanogaster corpus allatum (CA) synthesize JHB3 from
      endogenous and exogenous precursors in vitro. We present evidence supporting the
      thesis that biosynthesis proceeds from precursor FA via initial epoxidation and
      terminal methylation on the basis of the following: (1) Methyl farnesoate is not
      epoxidized to JHIII or JHB3; (2) Authentic JHIII is not epoxidized to JHB3; and
      (3) FABE is markedly metabolized to JHB3. Cerebral allatostatic factors act at
      some stage subsequent to FA and this precursor is not normally rate-limiting.
      Additionally, neural inhibition from the brain acts at some biosynthetic step
      prior to FA.

PMID- 7579572
TI  - Genetic and molecular studies of apterous: a gene implicated in the juvenile
      hormone system of Drosophila.
AB  - The apterous (ap) gene in Drosophila melanogaster encodes a homeodomain
      transcription factor. It is required for the development of the wings and of a
      subset of embryonic muscles. The gene has been implicated in the juvenile hormone
      (JH) system because mutations in ap lead to JH deficiency, and are associated
      with defective histolysis of the larval fat body, arrested vitellogenesis,
      sterility, and aberrant sexual behavior, all of which are dependent on JH. We
      describe here the use of hemizygotes and germ-line clones, of X-ray- and hybrid
      dysgenesis-induced lethal ap alleles to determine the primary role of the gene
      during development. We find that ap lethality is polyphasic, but occurs primarily
      at the larval and pupal stages. The lethal phenotype is not associated with any
      overt morphological abnormality, suggesting that death occurs from a systemic
      malfunction. Strong interallelic complementation for the wing phenotype was found
      between some ap mutations induced by X-rays or by hybrid-dysgenesis. By Northern
      blot analysis, we demonstrate an increase in ap expression in pupae and adults as
      compared to embryos and larvae, suggesting that it is developmentally regulated.
      Finally, primer extension is used to determine the transcription start site of
      the gene.

PMID- 7579575
TI  - Regulation and consequences of cellular changes in the prothoracic glands of
      Manduca sexta during the last larval instar: a review.
AB  - The prothoracic glands of the tobacco hornworm, Manduca sexta, respond to
      prothoracicotropic hormone (PTTH) by a regulatory pathway involving cAMP, protein
      phosphorylation, protein synthesis, and enhanced secretion of ecdysteroids
      including ecdysone and 3-dehydroecdysone. Recent investigations have revealed
      that PTTH acts by this general mechanism throughout the fifth larval instar,
      i.e., during the transition from larva to pupa. However, the glands undergo
      developmental changes in size, steroidogenic capacity, and in elements of the
      signalling pathway associated with synthesis, degradation, and intracellular
      action of cAMP. The present review describes such changes, and their possible
      regulation and consequences, in the general context of endocrine events
      underlying larval-pupal metamorphosis during the fifth larval stage.

PMID- 7579576
TI  - Recent advances in radioimmunoassay technology for the juvenile hormones.
AB  - Recent refinements in juvenile hormone radioimmunoassay technology now make this
      method significantly more sensitive and easier to use. Rabbit polyclonal antisera
      against (10R) JH III and racemic JH II have been developed to determine hemolymph
      hormone titers in the low picogram range. The antisera display minimal cross
      reactivity with JH metabolites, JH analogs, and hemolymph lipids. One antiserum
      recognizes racemic JH I, II, and (10R) III almost equivalently, exhibiting 50%
      displacement between 100 and 130 pg per tube. Another antiserum is JH II-specific
      and exhibits 50% displacement at 35 pg per tube. Assay sensitivity has been
      enhanced by using (10R,11S) [methyl-3H]-JH II of very high specific activity (>
      80 Ci/mmol) generated with Hyalophora cecropia accessory gland S
      adenosylmethionine transferase and S-[methyl-3H]-adenosyl-L-methionine.
      Preparation of biological samples has been simplified with overall recoveries of
      JH from hemolymph ranging between 60 and 75%.

PMID- 7579577
TI  - Immunological studies on the developmental and chromosomal distribution of
      ecdysteroid receptor protein in Chironomus tentans.
AB  - Antisera were raised against different domains of a putative ecdysteroid receptor
      (cEcRH) of Chironomus tentans. All the antisera reacted with a 68,000 dalton
      protein exhibiting DNA binding properties. Additionally, we were able to
      demonstrate that the antisera immunoprecipitate protein which binds a
      radioactively labeled ecdysteroid (Ec), i.e., [3H]ponasterone A, with high
      specificity. These properties indicate that the antisera recognize specifically
      an endogenous ecdysteroid receptor protein (cEcR) in C. tentans cells and thus
      are suitable for the following quantitative and qualitative immunological and
      immunohistochemical investigations. The cellular level of cEcR varies during
      development, and it is particularly low in oligopausing larvae. In polytene
      chromosomes of prepupal salivary glands, cEcR is located at approximately 50
      transcriptionally active loci. These loci include both early ecdysteroid (Ec)
      inducible puff sites, such as the locus containing the gene coding for the
      homolog of the E75 protein in Drosophila melanogaster, as well as late Ec
      inducible puff-sites. The latter group comprises a locus of a gene specifying the
      homolog of the D. melanogaster ultraspiracle protein. However, loci of genes
      coding for salivary gland secretory proteins (e.g., Balbiani ring forming
      chromosome regions) do not specifically react with the antisera. Thus, the
      developmental regulation of these genes is not directly controlled by Ec.
      Polytene chromosomes of oligopausing larvae show hardly any loci that contain
      cEcR. The few detected correspond, with few exceptions, to the most potent cEcR
      binding sites found in prepupae.

PMID- 7579578
TI  - The cloning and sequencing of cervine interleukin 10.
AB  - We report the cloning and sequencing of the cervine interleukin-10 gene. Specific
      cDNA was amplified by PCR using primers based on the bovine sequence. This was
      cloned into pGEM 5Zf and several clones were sequenced. The 762 nucleotide
      product coded for a 179 amino acid protein which was 86% homologous with its
      bovine and 77% homologous with its human counterparts. There is a strongly
      hydrophobic signal sequence consisting of the first 20 amino acids and a
      potential glycosylation site at amino acids 134-136. There are three regions,
      comprising 34% of the protein, which show complete homology between the cervine,
      bovine and human sequences. The transcription of the gene was shown by Northern
      Blotting where a single, 1.8kb, mRNA transcript was detected 4-8 hours after
      activation of peripheral blood mononuclear cells with mitogen.

PMID- 7579579
TI  - Cloning and sequence of the feline max, and max 9 transcripts.
AB  - Max is the recently discovered heterodimeric partner of the human myc oncogene
      product. In this report we describe the cloning and sequencing of two
      differentially spliced transcripts of the feline max gene. Previously published
      data have shown both myc and max to be highly conserved amongst species, and
      indeed there is a 100% homology between feline max and max, while the murine
      equivalent myn is 98% homologous at the amino acid level, with the nucleotide
      sequences showing a similarity of 98% and 95% respectively.

PMID- 7579582
TI  - The gtcRS operon coding for two-component system regulatory proteins is located
      adjacent to the grs operon of Bacillus brevis.
AB  - We identified, cloned and sequenced an operon comprising of two genes gtcR and
      gtcS located adjacent to the grs operon of Bacillus brevis, which encodes the
      multienzymes involved in the biosynthesis of the peptide antibiotic gramicidin S.
      The transcription initiation site of the gtcRS operon was determined in Bacillus
      brevis and Bacillus subtilis. The encoded proteins GtcR and GtcS were identified
      as members of the two-component system family of signal transducing proteins.

PMID- 7579580
TI  - Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human
      placental cDNA library.
AB  - A cDNA clone encoding bone morphogenetic protein-4 (BMP-4) has been isolated from
      a human placental cDNA library. Sequence analysis of this clone revealed that the
      nucleotide sequence of 5' region was different from that of human osteosarcoma
      BMP-4 and the deduced amino acid sequence indicated deletion of N-terminal 6
      amino acids. We confirmed the expression of this type of BMP-4 mRNA in one human
      osteogenic cell line in addition to the placenta by the polymerase chain reaction
      (PCR).

PMID- 7579584
TI  - A homolog of an Escherichia coli phosphate-binding protein gene from Xanthomonas
      oryzae pv. oryzae.
AB  - A Xanthomonas oryzae pv. oryzae gene with sequence similarity to an Escherichia
      coli phosphate-binding protein gene (phoS) produces a periplasmic protein of
      apparent M(r) 35,000 when expressed in E. coli. Amino terminal sequencing
      revealed that a signal peptide is removed during transport to the periplasm in E.
      coli.

PMID- 7579583
TI  - Sequence analysis of leukotoxin secretion determinants from a Pasteurella
      haemolytica-like organism.
AB  - The pHLBD genes encoding the secretion functions for the 105 kDa RTX leukotoxin
      of Pasteurella haemolytica-like (PHL) organism has been cloned and sequenced.
      Like analogous genes from other RTX determinants, the pHLBD genes lie immediately
      downstream from the leukotoxin structural gene, pHLA. Although isolated from a
      diverse group of gram-negative organisms, the pHLBD genes and the characterized
      RTX BD genes from other organisms exhibit a high degree of homology at both the
      DNA and predicted amino acid sequence levels. We have previously reported the
      cloning of the leukotoxin gene (pHLCA) (Chang et al., Infect. Immun. 61:2089
      2095), which encodes a 105-kda polypeptide with cytotoxic activity. DNA sequence
      analysis of the pHLBD genes shows 83.93% and 86.05% homologous to that of P.
      haemolytica IktBD genes, respectively.

PMID- 7579581
TI  - Cloning and characterization of Wnt-4 and Wnt-11 cDNAs from chick embryo.
AB  - We have isolated two members of the Wnt gene family, Wnt-4 and Wnt-11, from chick
      embryo cDNA library, and determined the entire coding sequences. The Wnt-4 and
      Wnt-11 genes encode secretory proteins composed of 351 and 354 amino acids,
      respectively, both having 24 Cys residues conserved among other Wnt family
      members. Alignment of the deduced amino acid sequences reveals that chicken Wnt-4
      and Wnt-11 are most similar to Xenopus Wnt-4 and mouse Wnt-11; respectively.
      Northern blot analysis indicates the Wnt-4 expression at 1.5 kilobase and the Wnt
      11 expression at 2.0 kilobase in the chick embryo.

PMID- 7579585
TI  - Cloning and sequencing of a murine cDNA encoding the proteasome component C5.
AB  - A cDNA encoding the mouse homologue to the rat and human component C5 of
      proteasome was isolated from a mouse ventral midbrain library. The deduced amino
      acid sequence shows 93% and 97.5% identity to the human and rat C5 component
      respectively.

PMID- 7579586
TI  - Cloning and chromosomal localization of a pseudogene corresponding to a mRNA for
      a soluble IL-6 receptor.
AB  - A polymerase chain reaction assay (Lust J.A. et al. (1992). Cytokine 4:96-100)
      was used to detect a mRNA coding for a soluble IL-6 receptor in human hepatoma
      cells. In addition to the expected amplification product, we found a sequence
      (SR4) which could be aligned to it with 78% identity. After cloning and
      sequencing a genomic 2.5-2.7 kB EcoRI fragment containing SR4, this sequence
      turned out to be part of a pseudogene corresponding to the transmembrane domain
      deleted soluble IL-6 receptor. Screening of a panel of interspecies hybrids
      revealed that it maps to chromosome 9.

PMID- 7579587
TI  - Identification and mapping of trnI, trnE and trnfM genes in the sunflower
      mitochondrial genome.
AB  - Three sunflower mitochondrial HindIII restriction fragments containing the tRNA
      genes trnI, trnE and trnfM have been sequenced. The genes are present in single
      copy on the whole genome and are transcribed. Hybridization experiments and
      sequence analysis of the HindIII fragments allowed the precise mapping and
      orientation of each gene on the sunflower mitochondrial genome.

PMID- 7579588
TI  - Human renin 5'-flanking DNA to nucleotide-2750.
AB  - Renin is one of the most important factors in blood pressure and electrolyte
      regulation in mammals and the renin locus has been implicated in hypertension. To
      assist studies of promoter control we therefore determined the 5'-flanking
      sequence of the human gene (REN) to residue -2750 relative to the transcription
      start site (+1). Sites of homology to consensus sequences for binding of trans
      acting factors involved in transcriptional control of other genes were
      identified, and functionality for two of these (a CRE and Pit-1 site) have so far
      been demonstrated.

PMID- 7579591
TI  - Bile acids as drugs: principles, mechanisms of action and formulations.
AB  - Bile acid therapy is based on the use of bile acid agonists or bile acid
      antagonists. Bile acid agonists consist of bile acids or their derivatives. They
      are used for two purposes. The first is to correct a deficiency in bile acids
      because of defective biosynthesis or intestinal conservation and thereby to
      restore bile acid function. This rationale may be termed replacement therapy. The
      second is to alter the composition of circulating bile acids and thereby to
      modulate cholesterol metabolism and/or decrease the cytotoxicity of the
      circulating bile acid pool. This rationale may be termed displacement therapy.
      Administration of chenodeoxycholic (CDCA) and/or ursodeoxycholic (UDCA) decreases
      biliary secretion of cholesterol leading to secretion of bile that is unsaturated
      in cholesterol and gradual dissolution of cholesterol gallstones. Administration
      of UDCA to patients with chronic cholestatic liver disease lowers the proportion
      of endogenous cytotoxic dihydroxy bile acids in the circulating bile acids,
      improves liver tests, and delays liver failure. Bile acid antagonists act to
      decrease intestinal conservation of bile acids either by sequestering bile acids
      in the intestinal lumen or by inhibiting bile acid transport by the ileal
      enterocyte. For therapy, CDCA is administered as the protonated acid and is well
      absorbed. UDCA is also administered as the protonated acid, but absorption is
      incomplete. Complete absorption can be obtained using the sodium salt of UDCA in
      a capsule with a pH-sensitive enteric coating. The taurine conjugate of UDCA is
      administered as the protonated sulfonic acid, and its absorption requires a
      carrier mechanism; however, it is likely to undergo rapid deconjugation during
      enterohepatic cycling, liberating UDCA which can be passively absorbed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579589
TI  - Nucleotide sequence and molecular variants of rat receptor-type protein tyrosine
      phosphatase-zeta/beta.
AB  - We have previously described the cloning of phosphacan, a chondroitin sulfate
      proteoglycan of nervous tissue which interacts with neurons, glia, neural cell
      adhesion molecules, and tenascin, and represents the extracellular domain of a
      receptor-type protein tyrosine phosphatase. We now report the complete cDNA and
      deduced amino acid sequences of the rat transmembrane phosphatase, and
      demonstrate that the phosphatase and the extracellular proteoglycan have
      different 3'-untranslated regions. Northern analysis showed three probable splice
      variants, comprising the extracellular proteoglycan (phosphacan) and long and
      short forms of the transmembrane phosphatase. PCR studies of rat genomic DNA
      indicated that there are no introns at the putative 5' and 3' splice sites or in
      the 2.6 kb segment which is deleted in the short transmembrane protein. Using
      variant-specific riboprobes corresponding to sequences in the 3'-untranslated
      region of phosphacan and in the first or second phosphatase domains of the
      transmembrane protein, in situ hybridization histochemistry of embryonic rat
      brain and spinal cord and early postnatal cerebellum demonstrated identical
      localizations of phosphacan and phosphatase mRNAs.

PMID- 7579592
TI  - The urea breath test: a non-invasive clinical tool for detecting Helicobacter
      pylori infection.
AB  - The urea breath test exploits the urease enzyme of Helicobacter pylori. The
      hydrolysis of labelled urea releases labelled carbon dioxide that is excreted in
      the breath. Distribution of urea throughout the stomach prevents sampling errors
      and allows for semiquantitative assessment of the extent of Helicobacter pylori
      infection. The urea breath test is very specific and sensitive and can be
      proposed as the method of choice for detecting Helicobacter pylori infection in
      ulcer patients before and after eradicating treatment as well as in
      epidemiological studies.

PMID- 7579590
TI  - Cholesterol nucleation in bile.
AB  - Protein factors, primarily glycoproteins, present in native human bile, have been
      found to modify, e.g., retard/accelerate, the process of de novo monohydrate
      crystal formation and, by inference, the rate of formation of cholesterol
      "nuclei" in such metastable cholesterol supersaturated systems. Neither the
      process of nucleation itself or how these modifiers work is yet well understood.
      From the health standpoint, an inhibitor type of protein has been found that may
      help explain why about 50% of the population have biliary cholesterol
      supersaturation; whereas, only about 10% actually form gallstones. To date, only
      one inhibitor glycoprotein has been isolated and characterized. Its role thus
      seems clear. This is in contrast to the situation with so-called promoter
      glycoproteins which accelerate nucleation and crystal formation. A number of
      these proteins have now been identified. An understanding of the comparative
      roles of each of these proteins has not yet been established. This is partly
      because of conflicting results, insufficient potencies or lack of information
      about physiologic concentrations.

PMID- 7579593
TI  - IFL- and ELISA-antigliadin antibodies recognize different antigenic reactivities
      from those of R1-antireticulin and antiendomysial antibodies.
AB  - In order to establish whether antigliadin antibodies, detected by indirect
      immunofluorescence (IFL-AGA), display the same antibody reactivity as ELISA-AGA
      or whether they cross-react with reticulin antibodies (R1-ARA and antiendomysial-
      EmA), sera from 16 untreated coeliac patients were repeatedly absorbed with crude
      gliadin dissolved in ethanol/water solution. The comparison between antibody
      activities before and after absorption demonstrated that IFL-AGA and ELISA-AGA
      are nothing but a single antibody, as both of them completely disappeared or
      markedly reduced their titre after incubation with crude gliadin. Moreover, AGA
      reactivity differs from the reactivity of antibodies directed against reticulin,
      as R1-ARA and EmA titres were not affected by crude gliadin absorption. The
      absolute absence of cross-reactivity between IFL-AGA and R1-ARA is further
      confirmed by the removal of the former and persistence of the latter after
      gliadin absorption in the 9 sera positive for both antibodies. Sera of coeliac
      patients, therefore, show only two discrete antibody reactivities, one directed
      to gliadin and the other to reticulin components.

PMID- 7579594
TI  - Alcoholic liver disease in alcoholic chronic pancreatitis: a prospective study.
AB  - The prevalence and characteristics of alcoholic liver disease (ALD) in patients
      with alcohol-induced chronic pancreatitis (AICP) are not well defined. Fifty
      consecutive patients undergoing surgery for AICP were investigated for evidence
      of ALD. In addition to preoperative functional and imaging assessment of the
      liver, all had liver biopsy during surgery. Hepatic biopsy results were as
      follows: 12 patients had normal liver and 10 minimal aspecific changes; of the
      remaining 28 patients, 7 had liver cirrhosis, 11 showed features of alcoholic
      hepatitis, 2 had moderate steatosis, 6 extrahepatic cholestasis, and the
      remaining 2 had a combination of alcoholic hepatitis and cholestasis. Of the 7
      patients with cirrhosis, 3 had oesophageal varices and 2 of these developed
      ascites in the postoperative period; in the remaining patients with ALD, this
      disease was subclinical. Patients with ALD consumed significantly (p < 0.005)
      more alcohol than those without ALD. In patients with cirrhosis, the duration of
      alcohol consumption (mean 27.6 years, range 18-42 years) was significantly longer
      (p < 0.05) than in patients without ALD (mean 19.7 years, range 8-36 years). The
      association of ALD with AICP is much more common than previously believed. The
      fact that AICP occurs earlier than liver cirrhosis and the fact that many
      patients stop alcohol consumption after the first attacks of pancreatic pain may
      explain, at least in part, the apparent rarity with which this association has
      been indicated by previous studies.

PMID- 7579595
TI  - Mallory-Weiss syndrome in a patient with hemophilia A and chronic liver disease.
AB  - Eighty percent of hemophiliacs exposed to plasma products are seropositive to
      hepatitis B and an even higher percentage are seropositive to hepatitis C. Post
      transfusion hepatitis is followed by cirrhosis in up to 25% of the cases. In the
      wake of portal hypertension, the development of oesophageal varices entails the
      risk of life-threatening hemorrhage. We report on a patient with moderate
      hemophilia A (factor VIII:C 4-11%) who suffered from massive hematemesis, melaena
      and evolving shock after excessive alcohol ingestion. The diagnosis of Mallory
      Weiss syndrome and the differential diagnosis of bleeding oesophageal varices as
      well as prognostic consequences are discussed.

PMID- 7579596
TI  - Lipohyperplasia of the ileocaecal valve as a cause of intestinal haemorrhage: an
      ultrasound Doppler study.
AB  - We present a case of lipohyperplasia of the ileocaecal valve causing intermittent
      intestinal bleeding visualized by Doppler ultrasound of the lower abdominal
      quadrant as an intestinal mass with intralesional arteriovenous fistula. These
      findings, never described before, are suggestive of highly vascularized lesions
      of the ileocaecal region and their recognition may avoid the need to perform an
      angiographic study of the superior mesenteric artery.

PMID- 7579597
TI  - Chemical sclerosing cholangitis after injection of scolicidal solution.
AB  - Sclerosing cholangitis may be due to developmental immunological, infective,
      vascular or chemical factors (1). Hydatid cysts of the liver may communicate with
      the biliary tree. This is the reason why intracystic injection of scolicidal
      solution before surgery may cause spreading of the solution into the bile ducts.
      This complication has already been described in literature (2,3). We present a
      new well-documented case of sclerosing cholangitis after the injection of
      formaldehyde into a hydatid cyst of the liver to kill it, and give some
      suggestions how to avoid this complication.

PMID- 7579598
TI  - Hospitalization rate and mean days of hospitalization of notified viral hepatitis
      cases in Italy. The Seieva Collaborating Group.
AB  - The hospitalization rate and the mean days of hospitalization of notified viral
      hepatitis cases in Italy were estimated by a specific surveillance system for
      acute viral hepatitis over the period 1987-1992. The hospitalization rate was
      very high, ranging from 88.8% for hepatitis A to 90.9% for non-A, non-B
      hepatitis. No changes were observed over time. For each type of hepatitis the
      highest figure was observed in the 15-24 year age group. The mean days of
      hospitalization of hepatitis B (24.2) and non-A, non-B (20.5) hepatitis was
      significantly higher (p < 0.05) than that of hepatitis A (16.5). The highest mean
      days of hospitalization of hepatitis A and B occurred in the 0-14 year age group,
      while for non-A, non-B hepatitis it was observed in subjects over 24 years of
      age. These findings indicate a nearly similar rate of hospitalization of all
      types of hepatitis. Hepatitis B and non-A, non-B hepatitis show a more prolonged
      course than hepatitis A.

PMID- 7579599
TI  - Epidemiology of hepatocellular carcinoma.

PMID- 7579600
TI  - Heterogeneity of HBV genome.

PMID- 7579601
TI  - Update on physical state of bile.
AB  - Because of recent assertions by a group of investigators that structures called
      "lamellae" instead of mixed micelles are present in human bile, the nature of
      biliary cholesterol solubilization and transport ("carriage") has again become a
      matter of dispute. "Lamellae" are rod- or tubular- shaped banded images observed
      when biles are negatively stained and dehydrated during electron microscopy; they
      are believed to be composed principally of biliary phospholipid (which is mostly
      lecithin) and cholesterol. It is well known that when mixed together in aqueous
      systems, lecithin and cholesterol, which are otherwise insoluble amphiphilic
      lipids, swell to form stacked or multilamellar liquid crystals that have regular
      periodicity because of the bilayer arrangement of the molecules. Provided super
      micellar concentrations of cholesterol are present, multilamellar vesicles occur
      spontaneously in concentrated model biles, and are a frequent occurrence in human
      gallbladder biles that are beginning to nucleate cholesterol crystals. When
      multilamellar vesicles are negatively stained and dehydrated, they produce
      "lamellae" images by electron microscopy. Coincidentally, images of "lamellae"
      are also produced when purely micellar bile, either model or native is treated
      similarly. In this review we show that these images are an artifact. This
      artifact is produced by the dehydration process itself and is due to a phase
      change i.e. a change in molecular packing which is predicted by the appropriate
      phase diagram. As a consequence, a dehydrated "lamellae" phase results and the
      overall effect is an electron microscopic image that is identical to those
      produced by multilamellar vesicles in supersaturated or lithogenic
      biles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579602
TI  - [An evaluation of the "ten year comprehensive cancer control strategy"].

PMID- 7579603
TI  - [Factors related to impaired mental function of elderly in a rural community].
AB  - Factors related to impaired mental function of the elderly population living in a
      rural community were analyzed in a study of 573 elderly residents (238 males, 335
      females) aged 70 years and over living in a village in the northeastern part of
      Japan. A comprehensive health and social survey including interviews and blood
      tests was performed in 1985. The major results obtained were as follows; 1)
      Mental function of the elderly declined with age and correlated with
      deterioration of physical function and frequencies of psychiatric symptoms. Those
      with deteriorated mental function tended to have histories of having
      cerebrovascular diseases and living with their children's household. 2) Multiple
      logistic regression model analysis revealed that the likeliness for impaired
      mental function (measured by Hasegawa's Mental Scale, a widely used scheme in
      Japan) was well explained by such independent variables as age, serum hemoglobin
      level, level of ability to feed oneself, social activities, and existence of
      anxiety. 3) Explanatory factors such as these are considered to be useful for
      public health nurses to detect in the community those who require further
      psychiatric attention and to facilitate early intervention to enable demented
      elderly to live in their own homes as long as possible.

PMID- 7579604
TI  - [Development and evaluation of self-study material for smoking prevention
      education].
AB  - A booklet for smoking prevention education was developed for junior high school
      students, which is a role-play activity book for self-study and discusses not
      only the harmful effects and dependency of smoking but also psychosocial factors
      affecting smoking behavior among students. The purpose of this material is to
      provide students with basic information needed to choose a non-smoking lifestyle
      even without a teacher's direct instruction. Process evaluation and impact
      evaluation studies were carried out between September 1991 and September 1992.
      Six hundred sixty-nine students and 9 teachers from three junior high schools in
      Osaka, Tokyo and Yamagata participated in the process evaluation study. More than
      90% of the students were able to complete the material in one school hour and
      less than 4% students expressed difficulty in learning from the booklet. Nine
      hundred seventy-seven students from 2 junior high schools in Tokyo participated
      in an intervention study to evaluate the effectiveness of the material. There
      were 500 students in the experimental school and 477 students in the control
      school. All students were given a pretest and posttest, 2 months apart. Knowledge
      concerning smoking increased and attitudes toward smoking were modified
      significantly in the experimental school. However, intention to smoke and smoking
      behavior did not change significantly, due to the small numbers of students with
      intention to smoke at the time of pretest and because there was not enough time
      for their intention to change. This study demonstrates the effectiveness of the
      material in junior high school. However, teacher participation during the
      instruction is also seen to be necessary for greater effect.

PMID- 7579605
TI  - [Factors related to choice of medical facilities by residents].
AB  - Using a study of 1,326 residents and 107 clinics in a city in the Tokai area,
      factors associated with patient selection of medical facilities were examined.
      Choice behaviors were divided into 2 separate levels: 1) choice behavior for the
      initial medical examination, 2) choice behavior in the case of treatment for
      chronic illness. The independent variables were 1) attitudes toward medical care,
      2) accessibility to medical facilities, and 3) health status. 1. Those
      interviewees who were older, who had continuing medical care after the first
      medical examination, and had strong interest in new treatment technology showed a
      strong tendency to elect to see physicians in hospitals for the first medical
      examination. 2. The group that had lower self-rated health, lower accessibility
      to medical facilities, and who did not work showed a strong tendency to see
      physicians in hospitals for chronic illnesses. 3. The data from clinics showed
      that more patients were introduced from clinics to hospitals than were introduced
      from hospitals to clinics. This result suggested that the one-sided stream of
      patients from clinics to hospitals was a part of the reason for a strong tendency
      for patients to elect to see physicians in hospitals.

PMID- 7579606
TI  - [Changes in the concentrations of nutrient components of human milk during
      lactation].
AB  - The total protein, lipid, lactose and calcium concentrations in breast milk were
      measured monthly from 1 month to 8-12 months postpartum in 26 lactating women. In
      order to determine whether changes in the milk composition were due to changes in
      the duration of lactation or the decline in the milk yield, or both, a linear
      regression analysis of the change rate of the milk composition against that of
      the milk volume was performed for the period from 5 to 12 months in 12 women for
      whom milk yield per day was measured in addition to the milk composition. Protein
      concentration decreased by about 30% during the first 6 months. Thereafter it
      increased significantly when the decrease in the milk yield was rapid but
      declined significantly when the decrease in the milk yield was gradual. The
      lactose concentration did not change during the first 10 months but somewhat
      increased thereafter. The calcium concentration remained steady during the 5
      months but decreased significantly thereafter. The rate of change for calcium was
      not affected by the extent of decline in milk yield. No significant changes were
      observed in lipid concentration and calculated energy content during the 12
      months of lactation.

PMID- 7579607
TI  - [Prevalence of urinary incontinence among institutionalized persons aged 60 and
      over in Japan].
AB  - In order to estimate the prevalence of persons experiencing urinary incontinence
      among the institutionalized aged 60 and over in Japan, a questionnaire survey was
      conducted in 16 prefectures in February 1991. The questionnaires were distributed
      and collected by the nurses in hospitals and in other facilities. A total of
      10,022 residents were asked to answer a questionnaire on their urinary
      incontinence condition and 9,798 responses were analysed. The main results were
      as follows; 1) The prevalence rate of urinary incontinence occurring almost daily
      in hospitalized persons aged 60 and over was 23.3% for men, 23.8% for women. 2)
      The prevalence rate of urinary incontinence occurring almost daily in
      institutionalized persons aged 60 and over in special nursing homes was 64.2% of
      the aged 60 and over for men, 67.9% for women. 3) The prevalence of urinary
      incontinence increased with age for both sexes especially in hospitalized
      persons. 4) The 95% confidence interval estimate for the number of the
      hospitalized over 60 years old suffering from almost daily urinary incontinent
      incidents was estimated to be from 31,000 to 113,000 in men and from 60,000 to
      182,000 in women. 5) The 95% confidence interval estimate for the number of the
      institutionalized in special nursing home over 60 years old suffering from almost
      daily urinary incontinent incidents was estimated to be from 34,000 to 50,000 in
      men and from 97,000 to 119,000 in women. 6) The 95% confidence interval estimate
      for the number of the institutionalized over 60 years old suffering from almost
      daily urinary incontinent incidents was estimated to be from 318,800 to 570,600
      in both sexes. 7) A random sampling survey is required to elucidate the actual
      state of prevalence in all generations. 8) Future research should emphasize the
      assessment of preventive and medical interventions, as incontinence is
      preventable and medical and surgical treatment options are available.

PMID- 7579608
TI  - [Progress of osteoporosis examinations in Shimura public health center].

PMID- 7579609
TI  - [Determinants of self-rated health among chronic hemodialysis patients].

PMID- 7579610
TI  - [Personnel requirements for health examination for 6 month and 9 mont-old
      children in municipalities in Japan].
AB  - Based on the Maternal and Child Health Law, municipalities offer health
      education, health counseling, health examination, and home visitation service for
      children and their mothers. In order to determine the personnel staffing
      requirements for the health examinations of 6 and 9 month-old children conducted
      independently by municipalities in Japan in 1989, data from the questionnaire
      survey executed by the Ministry of Health and Welfare in 1990 was analyzed.
      Questionnaires were sent to all municipalities and there were 3,198 responses for
      a response rate of 97.9% Results showed that in 1989, 27.5% of the 3,198
      municipalities were able to perform health examinations for 6 month-old children
      and 24.7% for 9 month-old children. In the case of those cities which had
      populations over 10,000 but under 20,000, about 30% were able to perform the
      health examinations for 6 and 9 month-old children independently. In those cities
      which had health Centers, the health personnel system most adequately supported
      these health examinations. Due to the lack of health personnel, rural towns and
      villages with small populations required public health nurses to be assisted by
      other staff, most often public health nurses from prefectural Health Centers. For
      example, in those areas with populations less than 3,000, about 42-45% of the
      total volume of the work required to be performed by public health nurses during
      the health examinations for 6 and 9 month-old children had to be covered by
      assistance from prefectural public health nurses.

PMID- 7579611
TI  - Evidence for proteolytic processing of tobacco mosaic virus movement protein in
      Arabidopsis thaliana.
AB  - Two ecotypes of Arabidopsis thaliana were transformed with the gene encoding
      tobacco mosaic virus (TMV) movement protein (P30). P30 accumulated largely in a
      subcellular fraction containing cell wall components and as a soluble protein.
      The protein migrated in denaturing gels with an M(r) of 30K, significantly faster
      than P30 (M(r) approximately 34K) accumulating after expression in transgenic
      tobacco, Escherichia coli or Spodoptera frugiperda cells, or after virus
      multiplication in tobacco. The P30 from A. thaliana infected with TMV for 14 days
      comigrated with that from E. coli, but that from A. thaliana infected for 49 days
      was of the smaller size. The use of antisera specific for the N- or C-termini of
      P30 showed that in A. thaliana P30 was proteolytically processed at the N
      terminus, a region essential for P30 function. The failure of these plants to
      complement a TMV P30 mutant indicated that processed P30 was nonfunctional,
      although the processing was not so rapid that it prevented the development of
      systemic infections with wild type TMV. The absence of detectable P30
      phosphorylation in A. thaliana demonstrated that phosphorylation was not
      essential for movement protein function and suggested that this species may use
      proteolytic cleavage of the N-terminus as an alternative strategy to tobacco for
      deactivating P30.

PMID- 7579612
TI  - Mutational analysis of the movement protein of odontoglossum ringspot virus to
      identify a host-range determinant.
AB  - Tobacco mosaic virus (TMV) which contains the movement protein (MP) of
      odontoglossum ringspot tobamovirus (ORSV) in place of the TMV MP systemically
      infects orchids but causes local infection in tobacco unless the carboxy-terminal
      48 amino acids of the MP are deleted (C. A. Holt, C. A. Fenczik, S. J. Casper,
      and R. N. Beachy; Virology, in press, 1995). Frameshift mutations were created
      within the 3' ends of the MP gene that led to truncations of the ORSV MP by 11,
      19, 28, 37, and 48 amino acids; each of the mutant MP genes was inserted into the
      cloned cDNA of TMV in place of the TMV MP and infectious transcripts were
      produced. Virus containing mutant MPs were used to infect vanilla orchids, a
      systemic host of ORSV, and tobacco plants. Removal of 11 amino acids from the
      ORSV MP prevented spread of the chimeric virus in orchids while restoring the
      ability to cause a systemic infection on tobacco. Further deletions of the MP
      affected the size of virus-induced necrotic local lesions on tobacco cv. Xanthi
      NN and the systemic spread and accumulation of virus in cv. Xanthi nn, a systemic
      host of TMV. However, each virus replicated to equivalent levels in protoplasts.
      A mechanism by which the ORSV MP limits the spread of the chimeric virus is
      proposed.

PMID- 7579613
TI  - Effective resistance to potyvirus infection conferred by expression of antisense
      RNA in transgenic plants.
AB  - Approximately 660 nt including the carboxy-terminal portion of the bean yellow
      mosaic potyvirus (BYMV) coat protein gene, complete 3' noncoding sequence and a
      short poly(A) tract were introduced to produce antisense RNA in transgenic
      Nicotiana benthamiana. Original (R0) transformants were selfed, and homozygous
      second generation (R2) populations challenged with infected sap, purified virus,
      or viral RNA. One transgenic line of 10 examined was extremely resistant to
      infection by mechanical inoculation of 100 micrograms/ml BYMV or 50 micrograms/ml
      BYMV RNA (the highest concentrations tested); no virus could be detected in
      inoculated leaves of this line. Nine other lines were systemically infected when
      inoculated with BYMV or BYMV RNA, with initial symptoms indistinguishable from
      those in nontransgenic plants. One of these lines subsequently developed reduced
      symptoms and then symptomless, virus-free leaves (complete recovery from BYMV
      infection), while other lines produced leaves with reduced symptoms and reduced
      virus titer compared to the controls (partial recovery). No transgenic lines had
      resistance to infection, nor recovery from symptom expression, following
      inoculation with pepper mottle or turnip mosaic potyviruses. Antisense RNA from
      3' regulatory regions can confer multiple degrees of resistance to potyviruses,
      including extreme resistanc to infection, presumably by interference in virus
      replication.

PMID- 7579614
TI  - Molecular characterization of the Pseudomonas syringae pv. pisi plasmid-borne
      avirulence gene avrPpiB which matches the R3 resistance locus in pea.
AB  - An avirulence gene (designated avrPpiB) from race 3 of Pseudomonas syringae pv.
      pisi was cloned and sequenced. The gene corresponded to a single open reading
      frame of 831 nt identified by transposon mutagenesis and subcloning. This ORF
      encodes a predicted hydrophilic protein of 276 amino acids (MW 31,300). It
      effects the expression of a resistance mechanism governed by a single genetic
      locus in pea. Cosegregation of resistance at the R3 locus of pea was observed
      towards race 3 and a transconjugant carrying the cloned avrPpiB gene according to
      the predicted 3:1 ratio of resistant:susceptible F2 progeny from a cross between
      Jade (R3 R3) and Kelvedon Wonder (rr) cultivars. DNA hybridization studies showed
      avrPpiB to be plasmid-borne in race 3 and suggested the presence of other alleles
      on one of the endogenous plasmids of races 1 and 7. Disruption of the avrPpiB
      allele of race 1 and its complementation confirmed its behavior towards pea
      cultivars expressing the R3 locus. Homologs of avrPpiB were detected in P.
      syringae pv. phaseolicola, P. syringae pv. maculicola, and P. syringae pv.
      tomato. The presence of avrPpiB homologs in P. syringae pv. phaseolicola does not
      match any gene-for-gene pattern of interaction with bean cultivars.

PMID- 7579615
TI  - Phylogenetic relationships of the soybean sudden death syndrome pathogen Fusarium
      solani f. sp. phaseoli inferred from rDNA sequence data and PCR primers for its
      identification.
AB  - Phylogenetic relationships of several species within the Fusarium solani-complex
      were investigated using characters from the nuclear ribosomal DNA. Genetic
      variation within 24 isolates, including 5 soybean sudden death syndrome (SDS)
      strains, was assessed using rDNA sequence data and restriction fragment length
      polymorphic markers. By these techniques, the causal agent of soybean SDS was
      identified as F. solani f. sp. phaseoli. In separate cladistic analyses,
      Plectosphaerella cucumerina and Nectria cinnabarina or F. ventricosum were used
      for rooting purposes. Monophyly of the F. solani-complex was strongly supported
      by bootstrap and decay analyses. Parsimony analysis indicates that this complex
      is composed of a number of phylogenetically distinct species, including
      Neocosmospora vasinfecta, F. solani f. sp. phaseoli, and biological species
      designated as MPI, MPV, and MPVI of N. haematococca. The results demonstrate
      complete congruence between biological and phylogenetic species within the N.
      haematococca-complex. In addition, DNA sequence data were used to design a PCR
      primer pair which could specifically amplify DNA from isolates of the SDS
      pathogen from infected plants.

PMID- 7579616
TI  - The HrpZ proteins of Pseudomonas syringae pvs. syringae, glycinea, and tomato are
      encoded by an operon containing Yersinia ysc homologs and elicit the
      hypersensitive response in tomato but not soybean.
AB  - The Pseudomonas syringae pathovars are composed of host-specific plant pathogens
      that characteristically elicit the defense-associated hypersensitive response
      (HR) in nonhost plants. P. s. pv. syringae 61 secretes an HR elicitor, harpinPss
      (HrpZPss), in a hrp-dependent manner. An internal fragment of the P. s. pv.
      syringae 61 hrpZ gene was used to clone the hrpZ locus from P. s. pv. glycinea
      race 4 (bacterial blight of soybean) and P. s. pv. tomato DC3000 (bacterial speck
      of tomato). DNA sequence analysis revealed that hrpZ is the second ORF in a
      polycistronic operon. The amino acid sequence identities of HrpZPss/HrpZPsg and
      HrpZPss/HrpZPst were 79 and 63%, respectively. Although none of the HrpZ proteins
      showed significant overall sequence similarity with other known proteins, HrpZPst
      contained a 24-amino acid sequence that is homologous with a region of the PopA1
      elicitor protein of the tomato pathogen, Pseudomonas solanacearum GMI1000. hrpA,
      the upstream ORF, was highly divergent: The amino acid sequence identities of
      HrpAPss/HrpAPsg and HrpAPss/HrpAPst were 91 and 28%, respectively, and no HrpA
      sequence showed similarity to known proteins. In contrast, the predicted products
      of the downstream ORFs in P. s. pv. syringae and P. s. pv. tomato, hrpB, hrpC,
      hrpD, and hrpE showed varying levels of similarity to those of yscI, yscJ, yscK,
      and yscL. These are colinearly arranged genes in the virC locus of Yersinia spp.,
      which are involved in the secretion of the Yop virulence proteins via the type
      III pathway. The similarity of the Ysc proteins was generally stronger in
      comparisons with the P. s. pv. tomato Hrp proteins.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579617
TI  - The complete hrp gene cluster of Pseudomonas syringae pv. syringae 61 includes
      two blocks of genes required for harpinPss secretion that are arranged colinearly
      with Yersinia ysc homologs.
AB  - Pseudomonas syringae pv. syringae 61 contains a 25-kb hrp cluster that is
      sufficient to elicit the hypersensitive response (HR) in nonhost plants. Previous
      studies have shown that mutations in complementation groups VIII, IX, and XI in
      the hrp cluster abolished the ability of the bacterium to cause the HR. The
      sequence of a 3.7-kb SmaI-SstI fragment covering groups VIII and IX now reveals
      five open reading frames (ORFs) in the same transcript, designated as hrpU, hrpW,
      hrpO, hrpX, and hrpY, and predicted to encode proteins of 14,795, 23,211, 9,381,
      28,489, and 39,957 Da, respectively. The hrpU, hrpW, hrpO, hrpX, and hrpY genes
      are homologous and arranged colinearly with the yscQ/spa33/spaO, yscR/spa24/spaP,
      yscS/spa9/spaQ, yscT/spa29/spaR, and yscU/spa40/spaS genes of Yersinia spp.,
      Shigella flexneri, and Salmonella typhimurium, respectively. These proteins also
      show similarity to Fli/Flh proteins of Bacillus and enteric bacteria. The Ysc and
      Spa proteins are involved in the secretion of virulence factors, like the Yop and
      Ipa proteins. Fli/Flh proteins are involved in flagellar biogenesis. The sequence
      of a 2.9-kb EcoRV-EcoRI DNA fragment containing mainly group XI revealed five
      ORFs, designated hrpC, hrpD, hrpE, hrpF, and hrpG, predicted to encode proteins
      of 29,096, 15,184, 21,525, 7,959, and 13,919 Da, respectively. The first three
      genes belong to an operon containing hrpZ, which encodes an extracellular protein
      that elicits the HR. hrpF and hrpG are two potential ORFs upstream of hrpH in the
      hrpH operon. HrpC is homologous to Yersinia YscJ, Pseudomonas solanacearum HrpI,
      Xanthomonas compestris pv. vesicatoria HrpB3, and Rhizobium fredii NolT. HrpE is
      similar to YscL of Yersinia spp. P. s. pv. syringae 61 Hrp proteins are most
      similar to Ysc proteins among those homologs. TnphoA insertions in hrpC, hrpE,
      hrpW, hrpX, and hrpY abolished the ability of P. s.pv. syringae 61 to secrete
      HrpZ (harpinPss), as determined by immunoblot analysis of cell-bound and culture
      supernatant fractions. Thus, many of the proteins required for flagellar
      biogenesis and virulence protein secretion in plant and animal pathogens may have
      a common ancestry.

PMID- 7579619
TI  - Mutational analysis of cauliflower mosaic virus gene VI: changes in host range,
      symptoms, and discovery of transactivation-positive, noninfectious mutants.
AB  - Gene VI of cauliflower mosaic virus (CaMV) has been shown to be a determinant of
      host specificity of the virus as well as a factor influencing symptom development
      in infected plants. In addition, it plays a crucial role in viral gene expression
      through a process of posttranscriptional transactivation. In the present study,
      linker-insertion mutations within gene VI of a cloned, recombinant cauliflower
      mosaic virus genome were constructed and tested for infectivity, symptom
      development on solanaceous plants, and the ability of transactivate viral gene
      expression. Certain mutations in the first third of the gene resulted in changes
      in symptoms shown by test plants. Another mutation, also in the first third of
      the gene, blocked infectivity in the Nicotiana species tested and systemic
      movement in Datura stramonium. The mutants were also tested in protoplasts for
      the ability to transactivate virus gene expression. Infectious mutants were
      invariably positive for transactivation and mutants negative for transactivation
      were noninfectious. Interestingly, two mutants positive for transactivation were
      noninfectious, suggesting a second function for gene VI in the infection process.
      These results further suggest a role for gene VI, as yet not fully understood, in
      systemic movement of the virus in infected plants.

PMID- 7579618
TI  - Pleiotropic effects of regulatory ros mutants of Agrobacterium radiobacter and
      their interaction with Fe and glucose.
AB  - Four exo mutants of Agrobacterium radiobacter, defective in the synthesis of
      acidic exopolysaccharide were complemented by a gene from that species, which is
      similar to the transcriptional regulator, ros, of A. tumefaciens. It was
      confirmed that this A. radiobacter gene, which we term rosAR, like ros, repressed
      its own transcription as well as that of virC and virD, two loci involved in
      tumorigenesis. The sequence of RosAR suggested that it might bind to a transition
      metal and its repressor abilities were shown to require Fe in the medium;
      repression was also enhanced with increasing levels of glucose. Certain rosAR
      mutants, in which its 3' end was removed were dominant; i.e., when plasmids
      containing such mutant forms of the gene were introduced into wild-type A.
      radiobacter, the transconjugants were nonmucoid. Such effects were also seen in a
      wide range of bacteria, including Escherichia coli and Xanthomonas. Several
      mutants that were complementd by rosAR also accumulated protoporphyrin,
      suggesting a defect in haem synthesis.

PMID- 7579621
TI  - A locus determining pathogenicity of Xanthomonas campestris is involved in
      lipopolysaccharide biosynthesis.
AB  - A pathogenicity locus in Xanthomonas campestris pv. campestris has been shown to
      comprise two genes which mediate biosynthesis of the bacterial lipopolysaccharide
      (LPS) but not extracellular polysaccharide. Mutants with Tn5 insertions in either
      gene showed alterations in the electrophoretic patterns of both water-soluble and
      phenol-soluble LPS forms, which suggested defects in the biosynthesis of the core
      oligosaccharide component. On gel chromatography, core oligosaccharides of the
      mutants were of apparently lower molecular weight than those from the wild type.
      Furthermore, the content of mannose and glucose, sugars characteristic of the
      core oligosaccharide, were significantly lower in the water-soluble LPS of the
      mutants. Because of their role in LPS core biosynthesis, the two genes were
      called rfaX and rfaY. rfaX mutants show altered behavior in a range of host and
      non-host plants such that the number of recoverable bacteria drop within the
      first 24 h after inoculation. In contrast, the behavior of rfaY mutants only
      differed from the wild type in Datura, a non-host plant in which the growth of
      the wild type is severely attenuated. The predicted protein RfaY showed
      significant sequence homology to a sub-family of RNA polymerase sigma factors
      which are involved in extracytoplasmic functions.

PMID- 7579620
TI  - A competitive polymerase chain reaction to quantify DNA of Leptosphaeria maculans
      during blackleg development in oilseed rape.
AB  - An assay based on the competitive polymerase chain reaction technique was
      developed to quantify Leptosphaeria maculans during blackleg disease development
      in oilseed rape leaves. By means of primers specific to the highly virulent type
      of L. maculans, a heterologous internal control template was prepared by
      amplifying and cloning DNA from Leptosphaeria korrae under low-stringency
      annealing conditions. Coamplification of L. maculans with the internal control
      DNA provided accurate quantification of 1 to 10(9) copies of target DNA. The
      assay was applied to a comparative study of L. maculans colonization of resistant
      and susceptible rape cultivars. The assay revealed that lesion size was
      associated with the quantity of L. maculans DNA during the first 12 days after
      inoculation of the susceptible cultivar Westar and the moderately resistant
      cultivar Legend. In these cultivars, the quantity of DNA per lesion increased
      during the first 12 days after inoculation and then declined. This decline in
      detectable fungal DNA coincided with abundant sporulation, rapid necrosis, and
      the onset of leaf senescence. Trace amounts of L. maculans DNA were detected in
      the resistant cultivar Glacier, in which lesion size was similar to that in the
      wounded, uninoculated check. The assay is rapid, accurate, and very sensitive and
      can be incorporated into conventional disease screening programs.

PMID- 7579622
TI  - Lipopolysaccharide from Xanthomonas campestris induces defense-related gene
      expression in Brassica campestris.
AB  - Purified lipopolysaccharide (LPS) from Xanthomonas campestris pv. campestris
      induced accumulation of transcript for beta-1,3-glucanase in turnip at
      concentrations of 1 micrograms/ml. The lipid A-inner core structure was required
      for activity but the O-antigen had no role. We suggest that release of LPS in
      planta triggers expression of at least some defense-related genes.

PMID- 7579624
TI  - Regulation of Agrobacterium tumefaciens virulence gene expression: isolation of a
      mutation that restores virGD52E function.
AB  - Expression of Agrobacterium tumefaciens virulence (vir) genes is controlled by
      virA, virG, and a plant inducer. Isolation of two constitutive mutants of the
      transcriptional activator virG, virGN54D, and virGI106L, that support vir gene
      expression in a virA independent manner has previously been reported.
      Characterization of virGN54D by several groups showed considerable variation in
      its ability to activate vir gene transcription. In this study we demonstrate that
      these differences can be accounted for by plasmid copy number. We report the
      isolation of a third constitutive mutation, virGI77V, that partially restores
      transcription activation function of a nonfunctional virG mutant, virGD52E. The
      second regulator, VirA, in its extreme C-terminus, contains a domain that is
      homologous to the N-terminal domain of VirG. Deletion of this domain of VirA
      leads to a fully constitutive phenotype.

PMID- 7579625
TI  - Synthetic antimicrobial peptide design.
AB  - To guide the design of potential plant pathogen-resistance genes, synthetic
      variants of naturally occurring antimicrobial gene products were evaluated. Five
      20-amino acid (ESF1, ESF4, ESF5, ESF6, ESF13), one 18-amino acid (ESF12), and one
      17-amino acid (ESF17) amphipathic peptide sequences were designed, synthesized,
      and tested with in vitro bioassays. Positive charges on the hydrophilic side of
      the peptide were shown to be essential for antifungal activity, yet the number of
      positive charges could be varied with little or no change in activity. The size
      could be reduced to 18 amino acids, but at 17 amino acids a significant reduction
      in activity was observed. ESF1, 5, 6, and 12 peptides were inhibitory to the
      germination of conidia from Cryphonectria parasitica, Fusarium oxysporum f. sp.
      lycopersici, and Septoria musiva but did not inhibit the germination of pollen
      from Castanea mollissima and Salix lucida. ESF12 also had no effect on the
      germination of Malus sylvestris and Lycopersicon esculentum pollen, but inhibited
      the growth of the bacteria Agrobacterium tumefaciens, Erwinia amylovora, and
      Pseudomonas syringae. The minimal inhibitory concentrations of the active ESF
      peptides were similar to those of the naturally occurring control peptides,
      magainin II and cecropin B. The significant differential in sensitivity between
      the microbes and plant cells indicated that the active ESF peptides are
      potentially useful models for designing plant pathogen-resistance genes.

PMID- 7579623
TI  - Expressed sequence tags of randomly selected cDNA clones from Eucalyptus globulus
      Pisolithus tinctorius ectomycorrhiza.
AB  - Random sequencing of cDNA clones from Eucalyptus globulus-Pisolithus tinctorius
      ectomycorrhizal tissues was carried out to generate expressed sequence tags
      (ESTs). Database comparisons revealed that 42% of the cDNAs corresponded to
      previously sequenced genes. These ESTs represent efficient molecular markers to
      analyze changes in gene expression during the formation of the ectomycorrhizal
      symbiosis.

PMID- 7579626
TI  - Asparaginyl endopeptidase mapping of proteins with subsequent matrix-assisted
      laser desorption/ionization mass spectrometry.
AB  - A matrix-assisted laser desorption/ionization (MALDI) mass spectrometric mapping
      strategy for the identification and characterization of isolated and purified
      proteins is described. The method, which employs the combined usage of a new site
      specific enzyme Asparaginyl endopeptidase (Asn-EP) for proteolysis, and MALDI for
      subsequent mass analysis, is capable of rapidly and sensitively examining the
      components of complex mixtures without any chromatographic or electrophoretic
      separation steps. Subpicomole sample quantities typically suffice to permit the
      confirmation of deduced primary structures and/or the identification of possible
      post-translational modifications. The data obtained should also prove useful for
      mass matching and sequence homology searching of computerised protein sequence
      data bases of known proteins.

PMID- 7579627
TI  - Amino acid sequence determination of phosphoenkephalins using liquid secondary
      ionization mass spectrometry.
AB  - Liquid secondary ionization mass spectrometry (LSIMS) operating in the positive-
      and negative-ion modes was used to study fragmentation profiles and to obtain the
      amino acid sequences of a set of seven phosphoenkephalin peptides. The use of
      glycerol as the liquid matrix led to increase in fragmentation of
      phosphopeptides. The prominent amino acid sequence-determining ions in the
      positive-ion mode are y-type C-terminal ions; the N-terminal sequence-specific
      ions are observed sporadically. The most dominant ions in those mass spectra,
      however, are the immonium ions and a few low-mass side-chain cleavage products.
      The mass spectra in the negative-ion mode are more information-rich, and provide
      data complementary to that from the positive-ion mode. The phosphate group marker
      ions, m/z 79 (PO-3) and 97 (H2PO-4), are prominent and both N- and C-termini
      sequence ions are formed with equal facility in this mode of analysis. Both
      positive- and negative-ion mass spectral data are useful in determining the amino
      acid sequence of all the seven phosphoenkephalins. Thus, LSIMS alone can be a
      viable option to the tandem mass spectrometry approach when sufficient quantities
      (> 50 nmol) of phosphopeptides are available.

PMID- 7579629
TI  - Disinfectants: actions and applications.

PMID- 7579628
TI  - Application of the fast-evaporation sample preparation method for improving
      quantification of angiotensin II by matrix-assisted laser desorption/ionization.
AB  - The fast-evaporation method of sample preparation has been applied for
      quantitative analysis using matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry. An instrumental protocol focusing on improvement of shot-to
      shot repeatability and compensation for signal degradation has been developed for
      quantification of angiotensin II using the fast-evaporation technique and an
      internal standard. The fast-evaporation method was compared to the standard
      method of sample preparation (using a multicomponent matrix) in the quantitative
      analysis of angiotensin II, and found to be superior in several respects.
      Improvement in sample homogeneity using the fast-evaporation method enhanced both
      point-to-point repeatibility and sample-to-sample reproducibility. The relative
      standard deviations of the analyte/internal standard ratios (point RSD) were
      decreased by a factor of three compared to those obtained using the
      multicomponent matrix method. The average point RSD was found to be ca. 5% for
      the fast-evaporation technique. Two internal standards were evaluated for
      quantification of angiotensin II. The better one, 1-SAR-8-Ile angiotensin II,
      yielded a relative standard deviation of the standard curve slope of ca. 2.2%
      over two orders of magnitude of concentration (45 nM to 3000 nM), an improvement
      by a factor of two over the standard preparation method. Renal microdialysate
      samples, spiked with angiotensin II and the internal standard 1-SAR-8-Ile
      angiotensin II, were also analyzed using the fast-evaporation technique. The
      detection limit was calculated to be in the high attomole range (675 amol).
      Furthermore, the accuracy for a single determination of angiotensin II
      concentration in these samples was found to be 13.9% with a relative error of
      8.19%.

PMID- 7579630
TI  - Use of disinfectants in open-air dairying.
AB  - Disinfection systems are essential in providing dairy foods which are safe for
      consumption by all sectors and age groups of the human population. The New
      Zealand dairy industry ensures quality competition under International
      Organisation for Standardisation (ISO) general systems standards (ISO 9002 and
      ISO Guide 25) and is subject to food safety assurance legislation (Dairy Industry
      Regulations 1990). This latter regulation requires that safe foods be produced in
      accordance with Product Safety Programmes approved by the Ministry of Agriculture
      and Fisheries. Safety can be demonstrated by compliance with the Codes of
      Practice of the industry. Farm dairy detergents and sanitisers must be approved
      for use. These disinfection systems are described.

PMID- 7579633
TI  - Use of antimicrobial agents in official abattoirs under meat inspection in the
      United States of America.
AB  - Facilities and equipment which are contaminated by a diseased carcass during
      slaughter and processing operations must be made free from microorganisms of
      human health concern before being used again. Therefore, a rapid-acting
      microbicidal agent is necessary to enable the swift resumption of operations.
      Currently, water heated to 180 degrees F (82.2 degrees C) is the antimicrobial
      agent of choice, as this rapidly kills microbes without leaving a residue which
      could jeopardize food products.

PMID- 7579632
TI  - Disinfection of stockyards.
AB  - Stockyards are premises where livestock from different sources are brought
      together for a period of time, before returning to their place of origin, or
      moving on to new premises or to the abattoir. Such premises pose particular
      problems for disease control, as they are potential sources for the dissemination
      of disease agents over wide geographical areas. The author describes a thorough
      programme of cleaning and disinfection for use during the routine operation of a
      stockyard. A different programme is described for use in the event of an outbreak
      of an Office International des Epizooties List A disease, taking into account the
      extra risks involved in such a disease outbreak.

PMID- 7579634
TI  - Cleaning and disinfection practice in the meat industries of Europe.
AB  - The application and efficacy of cleaning and disinfection methods are reviewed,
      together with the relevant European and French legislation. European Commission
      Hygiene Directive 93/43/EEC of 14 June 1993 proposes the adoption of hazard
      analysis and critical control points (HACCP) for the meat industry, and this
      includes cleaning and disinfection. It is necessary to organise a team for
      washing, cleaning, rinsing, disinfection and final rinsing; three different types
      of organisation are compared. Application of HACCP and its contribution to the
      shelf life of products and their contamination with Listeria monocytogenes is
      discussed in the light of practical experience with poultry meat and cured pork
      products. Various means of verifying the efficacy of cleaning and disinfection
      (turbidimetry, adenosine triphosphate assay and macroscopic observation) are
      compared with the techniques of conventional microbiology. The authors conclude
      that cleaning and disinfection are essential for application of HACCP to the meat
      industry.

PMID- 7579635
TI  - Disinfection of food production areas.
AB  - Disinfection, other than by heat, is ineffective unless all surfaces have
      previously been thoroughly cleaned to remove interfering materials. Cleaning is
      therefore extremely important as part of a two-stage cleaning and disinfection
      (sanitation) programme. The author describes the principles of sanitation, the
      chemicals and equipment involved, and the programme of events to be followed. For
      food products of 'low risk' (in terms of stable shelf life and safety),
      traditional sanitation programmes are adequate and in some cases disinfection may
      not be required. However, disinfection is essential for 'high-risk' food
      products, but this cannot be effectively undertaken without due consideration of
      hygienic design and possible cross-contamination. To ensure continued
      satisfactory performance of a sanitation programme, routine assessments should be
      undertaken.

PMID- 7579636
TI  - Application of disinfectants in poultry hatcheries.
AB  - Veterinary control and routine sanitary procedures in commercial poultry
      hatcheries should include the following: choice of a suitable geographical
      location to ensure an isolated site; proper hatchery design with separation of
      major operations; one-way flow of work within the hatchery; adequate ventilation
      of each room; routine cleaning and disinfection; formaldehyde fumigation or
      alternative method for disinfection of eggs, equipment and incubators; a routine
      programme for monitoring microbial contamination levels within the hatchery.

PMID- 7579631
TI  - Disinfecting poultry production premises.
AB  - Hygiene and sanitation play a major role in any effective disease control
      programme for poultry production premises. One of the important requirements to
      facilitate hygiene and sanitation is adoption of the 'all-in/all-out' method
      (i.e. all the birds within a single establishment should be of the same age
      group), together with the restriction of each enterprise to a single type or
      species of bird. Poultry premises and buildings should comply with requirements
      for isolation from the environment and strict observance of principles of hygiene
      and disease prevention (e.g. restrictions on movement of staff, equipment and
      vehicles). A poultry site must be prepared methodically for the entry of each new
      batch (removal of birds, litter and manure; vector and rodent control; dry and
      wet cleaning; disinfection; fumigation). Attention should be paid to the terminal
      sanitation of houses and equipment after depopulation (physical and chemical
      cleaning, pressure washing, disinfection, fumigation). Particular care should be
      exercised in the performance of sanitary procedures after a disease outbreak.
      Immediate disposal of dead and diseased birds is an important and effective tool
      in preventing the dissemination of any disease. Disposal methods include the use
      of burial pits, tanks, burial in trenches, burning, rendering and composting.
      Regular visual inspection, together with routine testing by microbiological
      monitoring methods, is very effective in checking the efficacy of cleaning and
      disinfection.

PMID- 7579637
TI  - Disinfection of farrowing pens.
AB  - The author presents details on the cleaning and disinfection of specialised
      farrowing accommodation within an intensive pig unit. Procedures are described
      for use in two quite different sets of circumstances, as follows: in the event of
      the occurrence of one of the major notifiable epizootic diseases; routine
      cleaning and disinfection as part of normal management procedures. In the former
      case, herd slaughter and the cleaning and disinfection of premises are required
      by law, in accordance with the protocol adopted by international agreement with
      reference to the specific disease concerned. In the latter case, cleaning and
      disinfection are not governed by statutes, and the protocol is established to
      suit the requirements of the individual unit, under the supervision of the farmer
      and the veterinary adviser.

PMID- 7579638
TI  - Disinfection procedures for personnel and vehicles entering and leaving
      contaminated premises.
AB  - Entry to and exit from contaminated premises--by animal health personnel,
      workers, owners, wildlife, insects, domestic animals and rodents--present a risk
      of disease spread which demands constant attention. The least expensive means of
      controlling and eliminating the risk of introducing virus and bacteria involves
      maintaining constant biosecurity programmes. These documented biosecurity
      measures and procedures must never be compromised by anyone, including the owners
      of premises. When time and the monetary investment involved in large and small
      animal production operations are considered, biosecurity precautions are a small
      investment cost in keeping the herd or flock free of infectious disease
      microorganisms.

PMID- 7579640
TI  - Disinfection in aquaculture.
AB  - The authors present information on the susceptibility to various disinfectants of
      some important pathogens in aquaculture, with special reference to the farming of
      salmonids. Practical disinfection procedures for use in the aquaculture industry
      are then described, on the basis of experience obtained in Norway and in other
      countries with a large salmon-farming industry. In addition to routine
      disinfection at aquaculture sites, the authors also describe disinfection
      procedures for use in outbreaks of notifiable diseases, as well as the
      treatment/disinfection of waste water and offal from the slaughtering and
      processing of aquaculture products.

PMID- 7579642
TI  - Use of disinfectants in zoos and game parks.
AB  - Disinfection is used in the animal quarters of zoos and game parks as an adjunct
      to physical cleaning and the removal of potentially contaminated materials.
      Disinfection is particularly useful in reducing infection risks in young animal
      nursery facilities, and in routine cleaning operations of animal quarters and
      feeding utensils. Specific disinfectants may be selected for certain known
      microbial contaminants following an infectious disease outbreak. For example,
      premises contaminated by foot and mouth disease virus are usually disinfected
      with 2% sodium hydroxide (lye). The disinfectants most commonly used in zoo
      operations usually have a broad spectrum of microbicidal activities, such as o
      phenylphenol salts, especially sodium o-phenylphenol. Equally popular for routine
      cleaning and sanitizing operations in zoos are quaternary ammonium compounds and
      chlorine bleach (sodium hypochlorite). It is important to remember that many
      disinfectants are protoplasmic poisons, or may be caustic or corrosive. Animals
      must usually be excluded from facilities being disinfected and premises should be
      rinsed thoroughly, after a suitable environmental exposure time to such
      disinfectants, before animals are allowed to return.

PMID- 7579641
TI  - Inactivation of viruses in liquid manure.
AB  - The stability of some viruses and methods of virus inactivation in liquid manure
      are reviewed. The authors discuss experimental data on the stability of foot and
      mouth disease virus, classical swine fever virus, Aujeszky's disease virus,
      African swine fever virus, swine influenza virus, porcine paramyxovirus, bovine
      virus diarrhoea virus and transmissible gastroenteritis of pigs virus.
      Recommendations and practical advice are given for the choice and application of
      chemical disinfectants for slurry.

PMID- 7579639
TI  - Disinfecting equine facilities.
AB  - Disinfection of equine premises provides a challenge to farm managers, in view of
      the variety of surfaces which may be contaminated and the wide variety of horse
      pathogens. Of the commonly occurring infectious diseases for which disinfection
      and disease control are especially important, rotavirus diarrhoea, salmonellosis
      and strangles are the most difficult to control. Phenolic disinfectants have been
      scientifically demonstrated to be effective in the presence of organic matter and
      are also virucidal. When used after thorough cleaning and rinsing of stall
      surfaces, phenolics have proved effective in controlling outbreaks of disease. In
      addition, 10% iodophors used for washing hands and cleaning equipment are also
      virucidal and bactericidal. Quaternary ammonium compounds, chlorhexidine, bleach
      and pine oil are readily available commercially, but are ineffective
      disinfectants in the presence of the organic matter encountered on horse farms.

PMID- 7579643
TI  - Disinfection and wildlife.
AB  - Capture, handling or transport of wildlife for purposes such as research, disease
      monitoring, wildlife damage control, relocation, and collection of zoological
      specimens can create risks of disease spread. Cleaning and disinfection
      procedures for equipment used in these activities must be routine and designed to
      eliminate the spread of pathogens to either animals or humans. General methods
      and materials for cleaning and disinfection apply to wildlife studies. Concepts
      involved in preparing a protocol specific to a wildlife investigation are
      discussed. The control of the spread of livestock and poultry pathogens via free
      ranging mammals and birds prior to disinfection of contaminated premises is
      approached through an accurate assessment of the problem and, where necessary,
      the selection of appropriate wildlife control measures. The authors discuss the
      development of a problem assessment, and review potential methods for use in the
      control of wildlife. For an accurate problem assessment, information is needed on
      the presence of wild mammals and birds at the site, exposure of wild mammals and
      birds to the pathogen, and the potential for further transmission. When wildlife
      control is deemed necessary, techniques may be selected to disperse or exclude
      animals from premises or to depopulate the site. Dispersal or exclusion from
      premises is appropriate when movement of animals within or away from the
      contaminated premises would not result in further transmission of the pathogen.
      Depopulation is necessary when the continued presence or dispersal of wild
      mammals or birds would potentially result in further spread of the disease.

PMID- 7579644
TI  - Writing guidelines to require disinfection.
AB  - Disinfection, when performed correctly, is an important step in the control and
      elimination of specific disease agents. Typical disinfection instructions merely
      state that 'the premises or materials contaminated by or exposed to disease shall
      be disinfected'. Directions are rarely given on how to perform the job. The first
      stage in a complete and proper disinfection operation for materials and property
      involves a thorough assessment of the problem and the development of a step-by
      step action plan. Detailed guidelines should address the relevant questions--who
      should do what? where, when and how?--in relation to each step of the job. It
      should be ensured that all work is correctly executed and reported, and a follow
      up evaluation of the premises should be made to verify that the disease agent(s)
      have been destroyed. Persons using disinfectants should always follow safety
      precautions to avoid the risk of occupational injuries.

PMID- 7579645
TI  - Engineering thermostability: lessons from thermophilic proteins.
AB  - As several groups begin to tap the rich pickings found in the Archaea--a vast
      kingdom that stretches the concept of life as we know it--the structures of
      proteins from hyperthermophiles are being elucidated. Certain features are
      beginning to emerge, such as compactness and hydrophobic clustering, but the
      ability to engineer these features into temperature-intolerant proteins is still
      some way off.

PMID- 7579646
TI  - Evidence on close packing and cavities in proteins.
AB  - The packing of a protein's constituent atoms and the attendant constraints placed
      upon them form the basis of many attempts to understand and predict protein
      structure, stability, folding and even function. Although the significance of
      packing is yet to be fully comprehended, recent experimental and theoretical
      investigations have increased our understanding through the description of
      mutational effects on structure and stability, determination of the limits of
      packing constraints for both protein folding and structure prediction, and
      delineation of packing guidelines on the basis of observed cavities in the native
      protein folds. These advances and allowing protein modellers, engineers and
      designers to tackle their problems from a more rational perspective.

PMID- 7579647
TI  - Helix design, prediction and stability.
AB  - Recent work revealing that our knowledge is now sufficient to build a reasonable
      quantitative model for the helix/coil transition in heteropolypeptides represents
      a watershed in research into alpha-helix stability, prediction and design. The
      opportunity is presented to design specific alpha-helix propensity patterns that
      may be used both to modify thermodynamic properties of target proteins and
      peptides, and for de novo protein design. Despite these advances, the picture is
      not yet complete and further studies of still poorly characterized factors are
      required to obtain a more precise understanding of alpha-helix stability.

PMID- 7579648
TI  - The emerging role of insertions and deletions in protein engineering.
AB  - Most attempts to engineer the properties of proteins have employed single or
      multiple substitution mutations, which typically produce minor changes in
      structure. Recent structural and stability studies of insertion and deletion
      mutants clearly indicate that relatively large structural perturbations can be
      induced by altering the spacing of residues along the polypeptide backbone, often
      without major losses in protein stability. Although their effects are difficult
      to anticipate, insertions and deletions provide important new tools for altering
      protein structures in directions not achievable with substitutions alone.

PMID- 7579649
TI  - Engineering membrane proteins.
AB  - Much of the research on integral membrane proteins mirrors that on soluble
      proteins; however, membrane protein engineering also has its own ends and means,
      many of which take advantage of the peculiar situation of membrane proteins,
      whose chains are distributed between one lipidic and two aqueous phases.
      Extramembrane loops have been shortened, cut, or elongated with segments forming
      proteolytic cleavage sites, foreign epitopes, extra transmembrane segments, or
      even whole proteins, with the aim of facilitating purification,
      biochemical/biophysical studies, or crystallogenesis. Transmembrane alpha-helices
      have been deleted, duplicated, exchanged, transported into a foreign context or
      replaced with synthetic peptides, in order to both understand their integration
      into, and assembly in, the membrane and unravel their functional role. Insertion
      of cysteine residues has been the basis for a great diversity of experiments,
      ranging from the exploration of secondary, tertiary and quaternary structures of
      the transmembrane region to the creation of anchoring points for reporter
      molecules. Chemical engineering--the synthesis of protein fragments or even of
      whole proteins--offers particularly exciting new prospects, given the small size
      of folding domains in alpha-helical membrane proteins. Membrane protein
      engineering is rapidly developing its own agenda of questions and tool chest of
      techniques.

PMID- 7579650
TI  - Peptide ligation and semisynthesis.
AB  - Semisynthesis is used to create defined analogues of proteins by the chemical
      manipulation of peptide fragments largely derived from the natural protein and
      the subsequent reassembly of those fragments into a near-native conformation. In
      common with the total synthesis of proteins, it requires efficient and non
      destructive methods for peptide religation. Recently, a wide range of
      chemoselective ligation schemes have been elaborated that now permit the assembly
      of minimally protected peptides from either synthetic or natural sources.

PMID- 7579651
TI  - Depletion and replacement of protein metal ligands.
AB  - Recently, site-directed mutagenesis has been applied to protein-derived metal
      ligands in a way that permits the replacement in trans of protein ligands. The
      chemical diversity of ligands available using this method far exceeds that
      attainable using standard mutagenesis. Non-conservative ligand replacement can
      yield novel metalloproteins with altered ligand-binding, enzymatic activities,
      and spectroscopic properties. Conservative ligand substitution, or 'ligand
      detachment', allows the structural and functional effects of the covalent linkage
      between the ligand and the protein to be evaluated; this linkage is often
      proposed to play a critical role in modulating the structure and reactivity of
      the metal center. Furthermore, this method can be exploited to study the details
      of molecular recognition at the structural, thermodynamic, and dynamic levels.

PMID- 7579652
TI  - Interfacial metal-binding site design.
AB  - In recent years, much attention has focused on the characterization of metal
      binding sites in natural metalloproteins and the design of novel metal-binding
      motifs. As a result, it is now possible to harness the high specificity and
      potency of metal-ion binding to modulate intermolecular interactions. Some
      encouraging results have been obtained using designed metal-binding sites in such
      diverse applications as the stabilization of artificial peptide assembly,
      regulation of membrane channels, control of enzyme activity and enhancement of
      hormone-receptor interactions.

PMID- 7579653
TI  - Protein engineering as a tool for crystallography.
AB  - The generation of large quantities of protein by overexpression technology has
      enabled structural studies of many important molecules that are found in only
      minute quantities in the cell. An increasing number of structures of proteins
      overexpressed in non-native systems have been solved. Crystallographers now have
      an extremely powerful tool, namely protein engineering, for the generation of
      native and derivative crystals that diffract to high resolution. The mutation of
      residues or generation of compact domains through truncation has resulted in
      crystals with enhanced diffraction properties. Heavy atom derivative crystals
      isomorphous to the native protein may also be engineered either by introducing
      cysteines or by removing cysteines whose reaction with heavy-atom compounds
      results in poor crystals.

PMID- 7579654
TI  - Designing DNA-binding proteins on the surface of filamentous phage.
AB  - The strategy of molecular evolution by phage display recently has been applied to
      the study of interactions between protein and DNA. This technology will
      imminently enable DNA-binding proteins to be made to measure. In the first
      instance, this will greatly advance our understanding of protein-DNA
      interactions, but in the long term, it is expected to yield powerful tools for
      use in medicine and research.

PMID- 7579655
TI  - Modeling mutations and homologous proteins.
AB  - A protein sequence with at lease 40% identity to a known structure can now be
      modelled automatically, with an accuracy approaching that o fa low-resolution X
      ray structure or a medium-resolution nuclear magnetic resonance structure. In
      general, these models have goods stereochemistry and an overall structural
      accuracy that is as high as the similarity between the template and the actual
      structure being predicted. As a result, the number of sequences that can be
      modelled is an order of magnitude larger then the number of experimentally
      determined protein structures. In addition, evaluation techniques are available
      that can estimated errors in different regions of the model. Thus, the number of
      applications where homology modelling is proving useful is growing rapidly.

PMID- 7579657
TI  - New strategies in protein design.
AB  - Initially, it was hoped that very simple rules could be sued to design proteins
      that embody all the characteristics of natural proteins. Indeed, with single
      domain proteins as targets, it has been possible to design proteins that adopt
      the desired global fold. Yet, designed proteins with well defined structures and
      properties that mimic those of natural proteins remain elusive. Recent efforts in
      protein design have been directed toward addressing the basis for non-native
      characteristics in most protein designs. Although it is clear that specific
      tertiary interactions between all residues in a protein contribute to the final
      folded state, much attention has been placed on optimizing the packing of side
      chains in the hydrophobic core, with substantial success.

PMID- 7579656
TI  - Theoretical approaches to designing novel sequences to fit a given fold.
AB  - One of the major goals of molecular biology is to understand how protein chains
      fold into a unique three-dimensional structure. Given this knowledge, perhaps the
      most exciting prospect will be the possibility of designing new proteins to
      perform designated tasks. The eventual pinnacle of protein engineering will be
      the fully automated design of a protein with novel structure and function.
      Achievement of this aim lies far in the future, although some early progress has
      been made recently.

PMID- 7579658
TI  - Sequence 'minimization': exploring the sequence landscape with simplified
      sequences.
AB  - The challenges of protein engineering arise, in part, from the enormous number of
      possible sequences and the almost unimaginably small fraction of such sequences
      that can be studied experimentally or computationally. Fortunately, not all
      possibilities need to be considered because many different sequences can adopt
      the same structure. Of the vast number of sequences that fold into a given
      conformation, some are 'simpler' than the sequences of typical proteins. Studying
      protein sequences that are simpler helps focus attention on the principal
      determinants of structure. Recent examples of this strategy are the
      simplification of protein surfaces and cores, the use of a binary 'code' for
      protein design and the structural analysis of random simple sequences.

PMID- 7579659
TI  - Protein engineering.

PMID- 7579660
TI  - Effects of rare codon clusters on high-level expression of heterologous proteins
      in Escherichia coli.
AB  - Within Escherichia coli and other species, a clear codon bias exists among the 61
      amino acid codons found within the population of mRNA molecules, and the level of
      cognate tRNA appears directly proportional to the frequency of codon usage. Given
      this situation, one would predict translational problems with an abundant mRNA
      species containing an excess of rare low tRNA codons. Such a situation might
      arise after the initiation of transcription of a cloned heterologous gene in the
      E. coli host. Recent studies suggest clusters of AGG/AGA, CUA, AUA, CGA or CCC
      codons can reduce both the quantity and quality of the synthesized protein. In
      addition, it is likely that an excess of any of these codons, even without
      clusters, could create translational problems.

PMID- 7579661
TI  - Gene fusion expression systems in Escherichia coli.
AB  - In recent years, Escherichia coli gene fusion expression systems have
      circumvented many of the problems inherent in the use of this bacterium for the
      production of recombinant proteins. These systems also provide a powerful means
      for identifying peptides or proteins with desired binding specificities. Gene
      fusion technology continues to expand with the introduction of new fusion
      partners, purification and detection tags, cleavage reagents and ways to display
      peptides on the surface of bacteria.

PMID- 7579662
TI  - Effects of overexpressing folding modulators on the in vivo folding of
      heterologous proteins in Escherichia coli.
AB  - Interest continues to increase in the use of folding modulators to overcome
      problems with heterologous protein folding in Escherichia coli. Currently, this
      approach, though highly successful with a number of individual proteins, remains
      a somewhat hit-and-miss affair. Ongoing research directed at unraveling the
      precise role and specificity of these folding modulators should generate a
      clearer understanding of the potential and limitations of overexpressing folding
      catalysts in vivo. This will facilitate the development, in the not too distant
      future, of a more structured and rational approach to improving the folding of
      heterologous gene products in E. coli.

PMID- 7579664
TI  - Production of recombinant proteins in the filamentous fungus Trichoderma reesei.
AB  - The potential of the filamentous fungus Trichoderma reesei for producing
      heterologous proteins has recently been demonstrated with a number of secreted
      proteins. Rate-limiting steps and ways of improving the production have been
      studied, especially using antibody Fab fragments. Major improvements have been
      achieved by producing the foreign protein fused to the fungal cellulase
      cellobiohydrolase I. In addition to the strong inducible cbh1 promoter, other
      promoters, which are regulated in a different manner, have been developed.

PMID- 7579665
TI  - Recombinant glycoprotein production in the slime mould Dictyostelium discoideum.
AB  - Dictyostelium discoideum is a well known amoeboid organism, with unicellular and
      multicellular life-cycle stages, that is used for studying cell and developmental
      biology. With advances in gene-disruption technology and transformation of this
      organism, many homologous proteins have been expressed either to complement
      defective proteins or to study basic cell biology. Now, D. discoideum is being
      used to express heterologous proteins that are difficult to study in other
      systems, and its unique cell biology is being exploited to facilitate a wide
      range of protein modifications. In the past year, substantial progress has been
      made in expressing correctly folded forms of malarial circumsporozoite antigen
      and rotavirus surface glycoprotein VP7. Exciting developments have also been made
      in expressing human muscarinic receptors.

PMID- 7579663
TI  - Advances in the use of Bacillus subtilis for the expression and secretion of
      heterologous proteins.
AB  - During the past year, significant progress has been made using Bacillus subtilis
      to produce a wide range of foreign proteins. Through strain improvement and co
      expression of molecular chaperones, secretory proteins can be produced at a
      higher level. Through protein engineering, target proteins can be redesigned to
      have better stability and solubility. A combination of these two strategies would
      be a useful approach to produce heterologous proteins from B. subtilis at high
      quality and with a high yield.

PMID- 7579666
TI  - Enhancing expression of recombinant proteins in mammalian cells using the
      herpesvirus VP16 transactivator.
AB  - The herpesvirus VP16 transactivator has become a useful tool for facilitating the
      production of recombinant proteins in cultured mammalian cells. Not only does it
      afford the rapid isolation of stable high-level producer cell lines, but also
      VP16-expressing cells have been found to rival COS cells in their ability to
      express proteins transiently. Some of the most interesting developments have been
      the expression of heterodimeric receptors and soluble forms of membrane proteins.

PMID- 7579668
TI  - Production of fully human antibodies by transgenic mice.
AB  - The ability to produce a diverse repertoire of fully human monoclonal antibodies
      may have significant applications to human therapy. One of the most promising
      approaches to the production of therapeutic human monoclonal antibodies is the
      creation of a mouse strain engineered to produce a large repertoire of human
      antibodies in the absence of mouse antibodies. Recently, such mice have been
      generated by introducing segments of human immunoglobulin loci into the germlines
      of mice deficient in mouse antibody production as a result of gene targeting.
      These mice produce significant levels of fully human antibodies with a diverse
      adult-like repertoire and, upon immunization with antigens, generate antigen
      specific fully human monoclonal antibodies. Such strains of mice may provide the
      optimal source for producing human monoclonal antibodies with high affinity and
      specificity against a broad spectrum of antigens, including human antigens.

PMID- 7579667
TI  - Production of monoclonal antibodies in COS and CHO cells.
AB  - Recent advances in the generation of genetically engineered monoclonal antibodies
      have enhanced the importance of COS cells as expression systems for rapidly
      producing sufficient quantities of these proteins for preliminary biochemical and
      biophysical analysis. In order to meet the demand for clinical supplies, a
      gradual increase has occurred in the usage of dihydrofolate reductase negative
      (DHFR-) Chinese hamster ovary (CHO) cells for large-scale antibody production.
      Using a variety of mammalian expression vectors and selection/amplification
      protocols, CHO cell lines capable of producing monoclonal antibodies at levels
      exceeding 1 gl-1 can now be obtained in an almost routine fashion. For the
      applications of monoclonal antibodies to expand into additional therapeutic
      areas, however, a 5-10-fold increase over current highest expression levels may
      still need to be achieved.

PMID- 7579669
TI  - Developments in expression cloning.
AB  - Recent years have seen a dramatic expansion in the range of applications of
      expression cloning techniques. New vectors and detection methods promise to
      further broaden the applicability of function-based screening approaches to
      problems in gene discovery. A major theme in the past year has been the
      introduction of engineered reporter cells that heighten the sensitivity with
      which clones expressing cDNAs can be identified.

PMID- 7579671
TI  - Expression systems.

PMID- 7579670
TI  - The use of adenoviral vectors for gene therapy and gene transfer in vivo.
AB  - Adenoviral vectors have proven to be excellent vehicles for gene delivery in vivo
      to a wide range of cell types. These vectors have been used to transfer genes
      such as CFTR to correct the defect in cystic fibrosis and, more recently, to
      supply serum blood factors and genetically modify tumors to enhance therapy.

PMID- 7579672
TI  - Laparoscopic transabdominal preperitoneal herniorrhaphy using abdominal wall
      lifting method under regional anesthesia: a preliminary report.
AB  - This report describes a laparoscopic transabdominal preperitoneal herniorrhaphy
      of groin hernias using an abdominal wall-lifting method under regional anesthesia
      as compared with pneumoperitoneum under general anesthesia. The series of studies
      involved the repair of 20 groin hernias; 7 hernias were direct, 11 were indirect,
      and 2 were femoral. These included 7 recurrent, 1 incarcerated, and 4 bilateral
      hernias. There were no intraoperative complications, and both procedures required
      no conversion to open surgery. There are no significant differences between the
      two groups in operative time and postoperative hospital stay. The only
      postoperative complication of our procedure was temporary inguinal pain in 2
      cases. The follow-up period ranged from 8 to 17 months. To date, no recurrence
      has developed. We conclude that our procedure is a safe, technically feasible,
      and useful method to perform laparoscopic herniorrhaphy for groin hernias.

PMID- 7579673
TI  - Laparoscopic adrenalectomy.
AB  - Laparoscopic adrenalectomy has already been described by various authors. The
      present series consists of 25 consecutive, nonselected cases operated on in the
      Department of Surgery, University of Pisa. All operations were carried out using
      a minimal access technique, and there were no conversions to open surgery. The
      mean operative time was 109 min. The median postoperative stay was 3 days (range
      2-5). There were no complications, and none of the patients required blood
      transfusion. This technique proved to be as safe as open surgery and caused less
      distress and allowed more rapid return to normal activity. Increased experience
      and the development of new laparoscopic equipment are expected to further reduce
      operative time.

PMID- 7579674
TI  - Acalculous cholecystitis: the use of diagnostic laparoscopy.
AB  - Acalculous cholecystitis (AC) carries a high mortality in the critically ill
      patient. This is partly due to the delay in its diagnosis. Clinical diagnostic
      examinations are often misleading. The purpose of our study was to evaluate the
      use of laparoscopy as a diagnostic tool in the evaluation of the critically ill
      patient suspected of having AC. From May 1993 to January 1994, we evaluated 10
      critically ill patients. Mean age was 56 years (range 17-90 years). Nine of the
      patients were trauma victims (8 blunt, 1 penetrating). The other patient was
      postcoronary bypass surgery. The laparoscopy was done after a mean of 15 days
      (range 6-54 days) after ICU admission. All patients were receiving ventilatory
      support, and all patients had elevated temperatures of greater than 38.5 degrees
      C. Five patients had abdominal tenderness, and 6 had elevated liver function
      tests (LFT). Six laparoscopies were done under local anesthesia and IV sedation
      at the bedside, and 4 were done in the operating room. All patients tolerated the
      procedure well with no complications. The laparoscopic findings were gangrenous
      cholecystitis in 2 patients. They both underwent laparoscopic cholecystectomies
      in the operating room. We elected to drain a very distended gallbladder in 1
      patient, who eventually was found to have an empyema of the chest. The other 7
      examinations were normal. Six of these patients recovered and were discharged.
      Our results suggest that laparoscopy can be used in the diagnosis of acalculous
      cholecystitis. Its positive and negative findings are valuable in the treatment
      of the critically ill. It can be done safely at the bedside.

PMID- 7579675
TI  - Bile leak following laparoscopic cholecystectomy.
AB  - The incidence and significance of bile leak after open cholecystectomy have been
      studied. The purpose of this study was to determine the incidence and
      significance of postoperative bile leak associated with both emergent and
      elective laparoscopic cholecystectomies. One thousand four hundred patients
      undergoing laparoscopic cholecystectomy from July 1990 to January 1995 were
      retrospectively reviewed. Twenty-seven percent of laparoscopic cholecystectomies
      were performed urgently for acute cholecystitis. Diisopropyl-iminodiacetic acid
      (DISIDA) scan was used to determine the presence of a bile leak or obstruction.
      Also, a subgroup of 63 patients from March to May of 1992 was studied in a
      nonblinded prospective fashion to determine the rate of asymptomatic bile leak.
      The incidence of bile leak in the subgroup of 63 patients was 4.7% (n = 3). All
      of these bile leaks were asymptomatic and of no clinical significance. The
      incidence of bile leak in the remaining 1337 was 0.14% (n = 2). These bile leaks
      were discovered by DISIDA scan following a workup of atypical abdominal pain
      following laparoscopic cholecystectomy. Both of these patients underwent ERCP
      with papillotomy. There were no ductal injuries in the entire series. Symptomatic
      bile leaks following laparoscopic cholecystectomy are rare. Asymptomatic bile
      leaks occur infrequently and are of no clinical significance.

PMID- 7579677
TI  - Laparoscopic feeding jejunostomy: a new technique.
AB  - Laparoscopic feeding jejunostomy has been performed and reported by others. The
      need for jejunostomy in certain patient populations, namely, patients with
      advanced head and neck cancer, esophageal cancer, or stomach cancer, is well
      accepted. This has led to numerous open techniques and now laparoscopic
      techniques. We describe in this report a new way of performing a laparoscopic
      jejunostomy and include intraoperative photographs.

PMID- 7579676
TI  - Bioavailability of medication after laparoscopic cholecystectomy.
AB  - Bioavailability of medication after laparoscopic cholecystectomy has not been
      studied previously. There is concern about the ability of patients to tolerate
      oral medication postoperatively and the optimal timing of hospital discharge. In
      this study, each subject received 20 mg/kg acetaminophen (po) preoperatively,
      with a repeat dose at 6 (group 1), 12 (group 2), or 24 h (group 3)
      postoperatively. Serum levels were obtained 40 and 90 min after each ingestion.
      Bioavailability of medication was significantly decreased (p < 0.01) 6 h (group
      1) and 12 h (group 2) postoperatively. Bioavailability returned to baseline by 24
      h after laparoscopic cholecystectomy (group 3). This study indicates that oral
      medication should be used judiciously during the first 12 h after laparoscopic
      surgery.

PMID- 7579679
TI  - Laparoscopic colostomy for a gunshot wound to the rectum.
AB  - The role of laparoscopy in the management of trauma patients is evolving. We
      describe a case of a laparoscopically created colostomy for treatment of a
      gunshot wound to the rectum.

PMID- 7579678
TI  - Gasless laparoscopic gastrostomy.
AB  - Percutaneous endoscopic gastrostomy (PEG) is the procedure of choice in the
      nutritional management of patients requiring gastrostomies. Laparoscopic
      gastrostomy is usually performed when PEG is contraindicated, for example, in
      patients with esophageal strictures, large gastric tumors, or a history of
      multiple abdominal surgery. We report herein a case of gasless laparoscopic
      gastrostomy performed for carcinoma associated with a severe respiratory distress
      syndrome in a malnourished patient with a tight esophageal stricture. The gasless
      technique uses the Laparolift System (Laparolift, Origin Medsystem, Inc.), a
      device composed of a fan-shaped retractor and a mechanical lifting arm that
      produces an abdominal wall distention resembling a truncated pyramid. Gasless
      laparoscopy was a safe alternative approach to CO2 pneumoperitoneum in this
      patient.

PMID- 7579681
TI  - Trocar site tumor recurrence after laparoscopic-assisted colectomy.
AB  - As a variety of procedures become technically feasible with laparoscopic
      techniques, it becomes increasingly important to appropriately select the
      patients who will benefit from the laparoscopic approach. We report the case of a
      patient with Dukes C2 colon cancer treated by laparoscopic-assisted sigmoid
      colectomy who subsequently developed an abdominal wall recurrence at a trocar
      site scar. The case raises some concerns about the use of the laparoscopic
      technique in the surgical management of colon cancer.

PMID- 7579680
TI  - Laparoscopic fenestration of giant posterolateral liver cyst.
AB  - A patient with a giant liver cyst in the posterolateral aspect of the right lobe
      successfully underwent laparoscopic fenestration. The procedure was facilitated
      by placing the patient in the lateral position, which provided direct access to
      the cyst.

PMID- 7579682
TI  - Small bowel obstruction following endoscopic extraperitoneal-preperitoneal
      herniorrhaphy.
AB  - Laparoscopic hernia repair has a number of unique potential complications. These
      include complications of pneumoperitoneum, general anesthesia, trocar injuries
      and complications of small bowel obstruction related to trocar site fascial
      defects, intraabdominal adhesions, and reaction with the synthetic mesh. A
      totally extraperitoneal approach should, in theory, eliminate postoperative small
      bowel obstruction in that the peritoneal space is never entered. A case of small
      bowel obstruction following totally extraperitoneal-preperitoneal herniorrhaphy
      is presented.

PMID- 7579683
TI  - Characterization of cis-regulatory elements of the c-myc promoter responding to
      human GM-CSF or mouse interleukin 3 in mouse proB cell line BA/F3 cells
      expressing the human GM-CSF receptor.
AB  - Interleukin 3 (IL-3) or granulocyte macrophage colony-stimulating factor (GM-CSF)
      activates c-fos, c-jun, and c-myc genes and proliferation in both hematopoietic
      and nonhematopoietic cells. Using a series of deletion mutants of the beta
      subunit of human GM-CSF receptor (hGMR) and inhibitors of tyrosine kinase, two
      distinct signaling pathways, one for activation of c-fos and c-jun genes, and the
      other for cell proliferation and activation of c-myc gene have been elucidated.
      In contrast to wealth of information on the pathway leading to activation of c
      fos/c-jun genes, knowledge of the latter is scanty. To clarify the mechanisms of
      activation of c-myc gene by cytokines, we established a transient transfection
      assay in mouse proB cell line BA/F3 cells expressing hGMR. Analyses of hGMR beta
      subunit mutants revealed two cytoplasmic regions involved in activation of the c
      myc promoter, one is essential and the other is dispensable but enhances the
      activity. These regions are located at the membrane proximal and the distal
      regions covering amino acid positions 455-544 and 544-589, respectively.
      Characterization of cis-acting regulatory elements of the c-myc gene showed that
      the region containing the P2 promoter initiation site is sufficient to mediate
      the response to mIL-3 or hGM-CSF. Electrophoretic mobility shift assay using an
      oligonucleotide corresponding to the distal putative E2F binding site revealed
      that p107/E2F complex, the negative regulator of E2F, decreased, and free E2F
      increased after mIL-3 stimulation. These results support the thesis that mIL-3 or
      hGM-CSF regulates the c-myc promoter by altering composition of the E2F complexes
      at E2F binding site.

PMID- 7579685
TI  - A large multigene family codes for the polypeptides of the crystalline trichocyst
      matrix in Paramecium.
AB  - The secretory granules (trichocysts) of Paramecium are characterized by a highly
      constrained shape that reflects the crystalline organization of their protein
      contents. Yet the crystalline trichocyst content is composed not of a single
      protein but of a family of related polypeptides that derive from a family of
      precursors by protein processing. In this paper we show that a multigene family,
      of unusually large size for a unicellular organism, codes for these proteins. The
      family is organized in subfamilies; each subfamily codes for proteins with
      different primary structures, but within the subfamilies several genes code for
      nearly identical proteins. For one subfamily, we have obtained direct evidence
      that the different members are coexpressed. The three subfamilies we have
      characterized are located on different macronuclear chromosomes. Typical 23-29
      nucleotide Paramecium introns are found in one of the regions studied and the
      intron sequences are more variable than the surrounding coding sequences,
      providing gene-specific markers. We suggest that this multigene family may have
      evolved to assure a microheterogeneity of structural proteins necessary for
      morphogenesis of a complex secretory granule core with a constrained shape and
      dynamic properties: genetic analysis has shown that correct assembly of the
      crystalline core is necessary for trichocyst function.

PMID- 7579684
TI  - Paxillin, a tyrosine phosphorylated focal adhesion-associated protein binds to
      the carboxyl terminal domain of focal adhesion kinase.
AB  - Focal adhesion kinase (pp125FAK or FAK) and paxillin colocalize with integrins in
      structures called focal adhesions. pp125FAK plays an important role in the
      transmission of integrin-induced cytoplasmic signals. Paxillin has also been
      implicated in cell signaling by virtue of its association with the protein
      tyrosine kinases pp60src and Csk (C-terminal Src kinase) as well as with the
      adapter/oncoprotein p47gag-crk. In this report we show that endogenous pp125FAK
      and paxillin form a stable complex both in vivo and in vitro and that this
      interaction is direct, requiring only pp125FAK and paxillin. The paxillin binding
      site on pp125FAK has been localized to the carboxy-terminal 148 residues of
      pp125FAK, but appears to be distinct from the previously identified focal
      adhesion-targeting sequence also present in the carboxy-terminal domain of
      pp125FAK. The interaction of paxillin and pp125FAK is independent of the adhesion
      of cells to the extracellular matrix, as the association can be detected in
      suspension cells as well as those attached to fibronectin.

PMID- 7579686
TI  - Specialized functional properties of the integrin alpha 4 cytoplasmic domain.
AB  - For functional studies of the integrin alpha 4 cytoplasmic domain, we have
      expressed the following in K562 and Chinese hamster ovary (CHO) cells: 1) wild
      type alpha 4 (called X4C4), 2) two chimeric forms of alpha 4 (called X4C2 and
      X4C5) that contain the cytoplasmic domains of alpha 2 and alpha 5, respectively,
      and 3) alpha 4 with no cytoplasmic domain (X4C0). Cytoplasmic domain exchange had
      no effect on VLA-4-dependent static cell adhesion or tethering to VCAM-1 in
      conditions of shear flow. However, the presence of the alpha 2 or alpha 5 tails
      markedly enhanced VLA-4-dependent K562 cells spreading (X4C2 > X4C5 > X4C4 >
      X4C0), increased localization of VLA-4 into focal adhesion-like complexes in CHO
      cells (X4C2 > X4C5 > X4C4), and strengthened CHO and K562 cell resistance to
      detachment from VCAM-1 in conditions of shear flow (X4C2 > X4C5 > X4C4 > X4C0).
      Conversely, the alpha 4 tail supported greater VLA-4-dependent haptotactic and
      chemotactic cell migration. In the absence of any alpha tail (i.e., X4C0), robust
      focal adhesions were observed, even though cell spreading and adhesion
      strengthening were minimal. Thus, such focal adhesions may have relatively little
      functional importance, and should not be compared with focal adhesions formed
      when alpha tails are present. Together, these results indicate that all three
      alpha-chain tails exert defined positive effects (compared with no tail at all),
      but suggest that the alpha 4 cytoplasmic domain may be specialized to engage in
      weaker cytoskeletal interactions, leading to diminished focal adhesion formation,
      cell spreading, and adhesion strengthening, while augmenting cell migration and
      facilitating rolling under shear flow. These properties of the alpha 4 tail are
      consistent with the role of alpha 4 integrins on highly motile lymphocytes,
      monocytes, and eosinophils.

PMID- 7579687
TI  - Import of stably folded proteins into peroxisomes.
AB  - By virtue of their synthesis in the cytoplasm, proteins destined for import into
      peroxisomes are obliged to traverse the single membrane of this organelle.
      Because the targeting signal for most peroxisomal matrix proteins is a carboxy
      terminal tripeptide sequence (SKL or its variants), these proteins must remain
      import competent until their translation is complete. We sought to determine
      whether stably folded proteins were substrates for peroxisomal import. Prefolded
      proteins stabilized with disulfide bonds and chemical cross-linkers were shown to
      be substrates for peroxisomal import, as were mature folded and disulfide-bonded
      IgG molecules containing the peroxisomal targeting signal. In addition, colloidal
      gold particles conjugated to proteins bearing the peroxisomal targeting signal
      were translocated into the peroxisomal matrix. These results support the concept
      that proteins may fold in the mammalian cytosol, before their import into the
      peroxisome, and that protein unfolding is not a prerequisite for peroxisomal
      import.

PMID- 7579688
TI  - Interspecies conservation of outer arm dynein intermediate chain sequences
      defines two intermediate chain subclasses.
AB  - Immunological analysis showed that antibodies against the intermediate chains
      (ICs) IC2 and IC3 of sea urchin outer arm dynein specifically cross-reacted with
      intermediate chains IC78 and IC69, respectively, of Chlamydomonas outer arm
      dynein. In contrast, no specific cross-reactivity with any Chlamydomonas outer
      arm polypeptide was observed using antibody against IC1 of sea urchin outer arm
      dynein. To learn more about the relationships between the different ICs,
      overlapping cDNAs encoding all of IC2 and IC3 of sea urchin were isolated and
      sequenced. Comparison of these sequences with those previously obtained for the
      Chlamydomonas ICs revealed that, although all four chains are homologous, sea
      urchin IC2 is much more closely related to Chlamydomonas IC78 (45.8% identity),
      and sea urchin IC3 is much more closely related to Chlamydomonas IC69 (48.5%
      identity), than either sea urchin chain is related to the other (23.5% identity).
      For homologous pairs, the similarities extend throughout the full lengths of the
      chains. Regions of similarity between all four ICs and the IC (IC74) of
      cytoplasmic dynein, located in the C-terminal halves of the chains, are due
      primarily to conservation of the WD repeats present in all of these ICs. This is
      the first demonstration that structural differences between individual ICs within
      an outer arm dynein have been highly conserved in the dyneins of distantly
      related species. The results provide a basis for the subclassification of these
      chains.

PMID- 7579690
TI  - ida4-1, ida4-2, and ida4-3 are intron splicing mutations affecting the locus
      encoding p28, a light chain of Chlamydomonas axonemal inner dynein arms.
AB  - We recently determined the nucleotide sequence of the gene encoding p28, a light
      chain of inner dynein arms of Chlamydomonas axonemes. Here, we show that p28 is
      the protein encoded by the IDA4 locus. p28, and the dynein heavy chains normally
      associated with it, are completely absent from the flagella and cell bodies of
      three allelic strains of ida4, named ida4-1, ida4-2, and ida4-3. We determined
      the nucleotide sequence of the three alleles of the p28 gene and found in each
      case a single nucleotide change, affecting the splice sites of the first, second,
      and fourth introns, respectively. Reverse transcriptase-polymerase chain reaction
      amplification of RNAs prepared from ida4 cells confirmed that these mutations
      prevent the correct splicing of the affected introns, thereby blocking the
      synthesis of full-length p28. These are the first intron splicing mutations
      described in Chlamydomonas and the first inner dynein arm mutations characterized
      at the molecular level. The absence in ida4 axonemes of the dynein heavy chains
      normally found in association with p28 suggests that p28 is necessary for stable
      assembly of a subset of inner dynein arms or for the binding of these arms to the
      microtubule doublets.

PMID- 7579689
TI  - The light chain p28 associates with a subset of inner dynein arm heavy chains in
      Chlamydomonas axonemes.
AB  - We show here that I2 and I3 inner dynein arm heavy chains of Chlamydomonas
      axonemes are resolved into two classes: one class associated with the protein p28
      and the other associated with the protein caltractin/centrin. We have determined
      the nucleotide sequence of the gene encoding p28, a light chain that, together
      with actin and caltractin/centrin, is associated with inner dynein arms I2 and I3
      of Chlamydomonas axonemes. p28 is a novel protein with affinity for a subset of
      the inner dynein arm heavy chains, but with no apparent significant homologies to
      tubulin- or actin-binding proteins. An antiserum specific for p28 showed that p28
      is present along the entire axoneme. The same antiserum coimmunoprecipitated p28,
      actin, and dynein heavy chains 2' and 2. In contrast, an anti-caltractin/centrin
      antiserum coimmunoprecipitated caltractin/centrin, actin, and the heavy chains 2,
      3, and 3'. It is likely that the dynein heavy chain 2 associated with p28,
      referred to as 2A, is a different polypeptide from dynein heavy chain 2 bound to
      caltractin/centrin, referred to as 2B. The complex formed by heavy chain 2B,
      actin, and caltractin/centrin is preferentially extracted by exposure to Nonidet
      P-40 and is missing in mutants lacking components 1 and 2 of the dynein
      regulatory complex.

PMID- 7579691
TI  - Integrin alpha 5 beta 1 expression negatively regulates cell growth: reversal by
      attachment to fibronectin.
AB  - Cells selected for overexpression of the integrin alpha 5 beta 1 show decreased
      proliferation and loss of the transformed phenotype. We provide evidence that de
      novo expression of the integrin alpha 5 beta 1 in HT29 colon carcinoma cells
      results in the growth arrest of these cells as characterized by reduced DNA
      synthesis and cellular proliferation in vitro. In fact, expression of integrin
      alpha 5 beta 1 on these cells induces the transcription of growth arrest specific
      gene 1 (gas-1), a gene product known to induce cellular quiescence, but blocks
      transcription of the immediate early genes c-fos, c-jun, and jun B. In vivo, the
      alpha 5 beta 1 transfectants display dramatically reduced tumorigenicity as well
      as a highly differentiated phenotype when compared with their pSVneo-transfected
      counterparts. Surprisingly, ligation of alpha 5 beta 1 on these cells by cell
      attachment to a fibronectin substrate not only reverses the growth inhibition and
      gas-1 gene induction but activates immediate early gene transcription. These
      findings demonstrate that integrin alpha 5 beta 1 expression in the absence of
      attachment to fibronectin activates a signaling pathway leading to decreased
      cellular proliferation and that ligation of this receptor with fibronectin
      reverses this signal, thereby contributing to the proliferation of transformed
      cells.

PMID- 7579692
TI  - The origin recognition complex in silencing, cell cycle progression, and DNA
      replication.
AB  - This report describes the isolation of ORC5, the gene encoding the fifth largest
      subunit of the origin recognition complex, and the properties of mutants with a
      defective allele of ORC5. The orc5-1 mutation caused temperature-sensitive growth
      and, at the restrictive temperature, caused cell cycle arrest. At the permissive
      temperature, the orc5-1 mutation caused an elevated plasmid loss rate that could
      be suppressed by additional tandem origins of DNA replication. The sequence of
      ORC5 revealed a potential ATP binding site, making Orc5p a candidate for a
      subunit that mediates the ATP-dependent binding of ORC to origins. Genetic
      interactions among orc2-1 and orc5-1 and other cell cycle genes provided further
      evidence for a role for the origin recognition complex (ORC) in DNA replication.
      The silencing defect caused by orc5-1 strengthened previous connections between
      ORC and silencing, and combined with the phenotypes caused by orc2 mutations,
      suggested that the complex itself functions in both processes.

PMID- 7579693
TI  - Human RNA polymerase II subunit hsRPB7 functions in yeast and influences stress
      survival and cell morphology.
AB  - Using a screen to identify human genes that promote pseudohyphal conversion in
      Saccharomyces cerevisiae, we obtained a cDNA encoding hsRPB7, a human homologue
      of the seventh largest subunit of yeast RNA polymerase II (RPB7). Overexpression
      of yeast RPB7 in a comparable strain background caused more pronounced cell
      elongation than overexpression of hsRPB7. hsRPB7 sequence and function are
      strongly conserved with its yeast counterpart because its expression can rescue
      deletion of the essential RPB7 gene at moderate temperatures. Further, immuno
      precipitation of RNA polymerase II from yeast cells containing hsRPB7 revealed
      that the hsRPB7 assembles the complete set of 11 other yeast subunits. However,
      at temperature extremes and during maintenance at stationary phase, hsRPB7
      containing yeast cells lose viability rapidly, stress-sensitive phenotypes
      reminiscent of those associated with deletion of the RPB4 subunit with which RPB7
      normally complexes. Two-hybrid analysis revealed that although hsRPB7 and RPB4
      interact, the association is of lower affinity than the RPB4-RPB7 interaction,
      providing a probable mechanism for the failure of hsRPB7 to fully function in
      yeast cells at high and low temperatures. Finally, surprisingly, hsRPB7 RNA in
      human cells is expressed in a tissue-specific pattern that differs from that of
      the RNA polymerase II largest subunit, implying a potential regulatory role for
      hsRPB7. Taken together, these results suggest that some RPB7 functions may be
      analogous to those possessed by the stress-specific prokaryotic sigma factor
      rpoS.

PMID- 7579694
TI  - The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and
      are components of a large protein complex.
AB  - During most of Drosophila development the regulation of homeotic gene
      transcription is controlled by two groups of regulatory genes, the trithorax
      group of activators and the Polycomb group of repressors. brahma (brm), a member
      of the trithorax group, encodes a protein related to the yeast SWI2/SNF2 protein,
      a subunit of a protein complex that assists sequence-specific activator proteins
      by alleviating the repressive effects of chromatin. To learn more about the
      molecular mechanisms underlying the regulation of homeotic gene transcription, we
      have investigated whether a similar complex exists in flies. We identified the
      Drosophila snr1 gene, a potential homologue of the yeast SNF5 gene that encodes a
      subunit of the yeast SWI/SNF complex. The snr1 gene is essential and genetically
      interacts with brm and trithorax (trx), suggesting cooperation in regulating
      homeotic gene transcription. The spatial and temporal patterns of expression of
      snr1 are similar to those of brm. The snr1 and brm proteins are present in a
      large (> 2 x 10(6) Da) complex, and they co-immunoprecipitate from Drosophila
      extracts. These findings provide direct evidence for conservation of the SWI/SNF
      complex in higher eucaryotes and suggest that the Drosophila brm/snr1 complex
      plays an important role in maintaining homeotic gene transcription during
      development by counteracting the repressive effects of chromatin.

PMID- 7579695
TI  - Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere
      protein with homology to the mammalian centromere protein CENP-C.
AB  - The MIF2 gene of Saccharomyces cerevisiae has been implicated in mitosis. Here we
      provide genetic evidence that MIF2 encodes a centromere protein. Specifically, we
      found that mutations in MIF2 stabilize dicentric minichromosomes and confer high
      instability (i.e., a synthetic acentric phenotype) to chromosomes that bear a cis
      acting mutation in element I of the yeast centromeric DNA (CDEI). Similarly, we
      observed synthetic phenotypes between mutations in MIF2 and trans-acting
      mutations in three known yeast centromere protein genes-CEP1/CBF1/CPF1,
      NDC10/CBF2, and CEP3/CBF3B. In addition, the mif2 temperature-sensitive phenotype
      can be partially rescued by increased dosage of CEP1. Synthetic lethal
      interactions between a cep1 null mutation and mutations in either NDC10 or CEP3
      were also detected. Taken together, these data suggest that the Mif2 protein
      interacts with Cep1p at the centromere and that the yeast centromere indeed
      exists as a higher order protein-DNA complex. The Mif2 and Cep1 proteins contain
      motifs of known transcription factors, suggesting that assembly of the yeast
      centromere is analogous to that of eukaryotic enhancers and origins of
      replication. We also show that the predicted Mif2 protein shares two short
      regions of homology with the mammalian centromere Ag CENP-C and that two
      temperature-sensitive mutations in MIF2 lie within these regions. These results
      provide evidence for structural conservation between yeast and mammalian
      centromeres.

PMID- 7579696
TI  - Sorting of yeast alpha 1,3 mannosyltransferase is mediated by a lumenal domain
      interaction, and a transmembrane domain signal that can confer clathrin-dependent
      Golgi localization to a secreted protein.
AB  - alpha 1,3 mannosyltransferase (Mnn1p) is a type II integral membrane protein that
      is localized to the yeast Golgi complex. We have examined the signals within
      Mnn1p that mediate Golgi localization by expression of fusion proteins comprised
      of Mnn1p and the secreted protein invertase. The N-terminal transmembrane domain
      (TMD) of Mnn1p is sufficient to localize invertase to the Golgi complex by a
      mechanism that is not saturable by approximately 15-20 fold overexpression.
      Furthermore, the TMD-mediated localization mechanism is clathrin dependent, as an
      invertase fusion protein bearing only the Mnn1p TMD is mislocalized to the plasma
      membrane of a clathrin heavy chain mutant. The Mnn1-invertase fusion proteins are
      not retained in the Golgi complex as efficiently as Mnn1p, suggesting that other
      signals may be present in the wild-type protein. Indeed, the Mnn1p lumenal domain
      (Mnn1-s) is also localized to the Golgi complex when expressed as a functional,
      soluble protein by exchanging its TMD for a cleavable signal sequence. In
      contrast to the Mnn1-invertase fusion proteins, overexpression of Mnn1-s
      saturates its retention mechanism, and results in the partial secretion of this
      protein. These data indicate that Mnn1p has separable Golgi localization signals
      within both its transmembrane and lumenal domains.

PMID- 7579697
TI  - Roles for Ca2+ stores release and two Ca2+ influx pathways in the Fc epsilon R1
      activated Ca2+ responses of RBL-2H3 mast cells.
AB  - Cross-linking the high affinity IgE receptor, Fc epsilon R1, with multivalent
      antigen induces inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-dependent release of
      intracellular Ca2+ stores, Ca2+ influx, and secretion of inflammatory mediators
      from RBL-2H3 mast cells. Here, fluorescence ratio imaging microscopy was used to
      characterize the antigen-induced Ca2+ responses of single fura-2-loaded RBL-2H3
      cells in the presence and absence of extracellular Ca2+ (Ca2+o). As antigen
      concentration increases toward the optimum for secretion, more cells show a Ca2+
      spike or an abrupt increase in [Ca2+]i and the lag time to onset of the response
      decreases both in the presence and the absence of Ca2+o. When Ca2+o is absent,
      fewer cells respond to low antigen and the lag times to response are longer than
      those measured in the presence of Ca2+o, indicating that Ca2+o contributes to
      Ca2+ stores release. Ins(1,4,5)P3 production is not impaired by the removal of
      Ca2+o, suggesting that extracellular Ca2+ influences Ca2+ stores release via an
      effect on the Ins(1,4,5)P3 receptor. Stimulation with low concentrations of
      antigen can lead, only in the presence of Ca2+o, to a small, gradual increase in
      [Ca2+]i before the abrupt spike response that indicates store release. We propose
      that this small, initial [Ca2+]i increase is due to receptor-activated Ca2+
      influx that precedes and may facilitate Ca2+ stores release. A mechanism for
      capacitative Ca2+ entry also exists in RBL-2H3 cells. Our data suggest that a
      previously undescribed response to Fc epsilon R1 cross-linking, inhibition of
      Ca2+ stores refilling, may be involved in activating capacitative Ca2+ entry in
      antigen-stimulated RBL-2H3 cells, thus providing the elevated [Ca2+]i required
      for optimal secretion. The existence of both capacitative entry and Ca2+ influx
      that can precede Ca2+ release from intracellular stores suggests that at least
      two mechanisms of stimulated Ca2+ influx are present in RBL-2H3 cells.

PMID- 7579698
TI  - Induction of carcinoma cell migration on vitronectin by NF-kappa B-dependent gene
      expression.
AB  - Integrin alpha v beta 5 promotes FG carcinoma cell adhesion to vitronectin yet
      requires protein kinase C (PKC) activation for migration on this ligand. Here we
      report that this PKC-dependent cell motility event requires NF-kappaB-dependent
      transcription. Specifically, a component within nuclear extracts prepared from
      PKC-stimulated FG cells exhibited a significant increase in binding activity to a
      synthetic oligonucleotide containing a consensus kappa B sequence. These nuclear
      DNA-binding complexes were shown to be comprised of p65 and p50 NF-kappaB/rel
      family members and appeared functionally active because they promoted
      transcription of a reporter construct containing a kappa B site. The NF-kappa B
      activation event was directly linked to the alpha v beta 5 motility response
      because the NF-kappa B-binding oligonucleotide, when introduced into FG cells,
      inhibited cell migration on vitronectin but not on collagen and had no effect on
      cell adhesion to either ligand. These results suggest that the detected DNA
      binding complexes interact with kappa B transcriptional elements to regulate gene
      expression required for alpha v beta 5-dependent cell motility on vitronectin.

PMID- 7579699
TI  - The metalloproteinase matrilysin is preferentially expressed by epithelial cells
      in a tissue-restricted pattern in the mouse.
AB  - To explore the role of the matrix metalloproteinase matrilysin (MAT) in normal
      tissue remodeling, we cloned the murine homologue of MAT from postpartum uterus
      using RACE polymerase chain reaction and examined its pattern of expression in
      embryonic, neonatal, and adult mice. The murine coding sequence and the
      corresponding predicted protein sequence were found to be 75% and 70% identical
      to the human sequences, respectively, and organization of the six exons
      comprising the gene is similar to the human gene. Northern analysis and in situ
      hybridization revealed that MAT is expressed in the normal cycling, pregnant, and
      postpartum uterus, with levels of expression highest in the involuting uterus at
      early time points (6 h to 1.5 days postpartum). The mRNA was confined to
      epithelial cells lining the lumen and some glandular structures. High
      constitutive levels of MAT transcripts were also detected in the small intestine,
      where expression was localized to the epithelial Paneth cells at the base of the
      crypts. Similarly, MAT expression was found in epithelial cells of the efferent
      ducts, in the initial segment and cauda of the epididymis, and in an extra
      hepatic branch of the bile duct. MAT transcripts were detectable only by reverse
      transcription-polymerase chain reaction in the colon, kidney, lung, skeletal
      muscle, skin, stomach, juvenile uterus, and normal, lactating, and involuting
      mammary gland, as was expression primarily late in embryogenesis. Analysis of MAT
      expression during postnatal development indicated that although MAT is expressed
      in the juvenile small intestine and reproductive organs, the accumulation of
      significant levels of MAT mRNA appears to correlate with organ maturation. These
      results show that MAT expression is restricted to specific organs in the mouse,
      where the mRNA is produced exclusively by epithelial cells, and suggest that in
      addition to matrix degradation and remodeling, MAT may play an important role in
      the differentiated function of these organs.

PMID- 7579700
TI  - A role for calmodulin in organelle membrane tubulation.
AB  - Membrane tubules of uniform diameter (60-80 nm) and variable lengths have been
      seen to extend from the main bodies of the Golgi complex, trans Golgi network
      (TGN), and endosomes. In the case of endosomes, these tubules appear to mediate
      membrane and receptor recycling events. Brefeldin A (BFA) is a potent drug that
      completely blocks coated vesicle formation from the Golgi complex and TGN, but at
      the same time causes the enhanced formation of membrane tubules from these same
      organelles. Recently, experiments have shown that calmodulin antagonists inhibit
      the transport of receptors out of endosomes, perhaps by inhibiting the formation
      of recycling tubules. Using the potent calmodulin-specific antagonists N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), N-(4-aminobutyl)-5-chloro-2
      naphthalenesulfonamide (W-13), and N-(4-aminobutyl)-5-chloro-1
      naphthalenesulfonamide (C-1), we found that the recycling of transferrin from
      endosomes to the cell surface was significantly inhibited, resulting in the
      formation of enlarged endosomal vacuoles. In addition, these same calmodulin
      antagonists also potently inhibited the formation of BFA-stimulated membrane
      tubules from the Golgi complex, TGN, and endosomes. In the case of the Golgi
      complex, failure to form tubules resulted in the inhibition of BFA-stimulated
      retrograde transport to the endoplasmic reticulum. These results suggest that
      calmodulin is a general regulator of membrane tubulation and is capable of
      influencing the morphology of several organelles.

PMID- 7579703
TI  - Insolubility and redistribution of GPI-anchored proteins at the cell surface
      after detergent treatment.
AB  - A diverse set of cell surface eukaryotic proteins including receptors, enzymes,
      and adhesion molecules have a glycosylphosphoinositol-lipid (GPI) modification at
      the carboxy-terminal end that serves as their sole means of membrane anchoring.
      These GPI-anchored proteins are poorly solubilized in nonionic detergent such as
      Triton X-100. In addition these detergent-insoluble complexes from plasma
      membranes are significantly enriched in several cytoplasmic proteins including
      nonreceptor-type tyrosine kinases and caveolin/VIP-21, a component of the
      striated coat of caveolae. These observations have suggested that the detergent
      insoluble complexes represent purified caveolar membrane preparations. However,
      we have recently shown by immunofluorescence and electron microscopy that GPI
      anchored proteins are diffusely distributed at the cell surface but may be
      enriched in caveolae only after cross-linking. Although caveolae occupy only a
      small fraction of the cell surface (< 4%), almost all of the GPI-anchored protein
      at the cell surface becomes incorporated into detergent-insoluble low-density
      complexes. In this paper we show that upon detergent treatment the GPI-anchored
      proteins are redistributed into a significantly more clustered distribution in
      the remaining membranous structures. These results show that GPI-anchored
      proteins are intrinsically detergent-insoluble in the milieu of the plasma
      membrane, and their co-purification with caveolin is not reflective of their
      native distribution. These results also indicate that the association of
      caveolae, GPI-anchored proteins, and signalling proteins must be critically re
      examined.

PMID- 7579702
TI  - VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes
      in vivo and in vitro.
AB  - VIP21-caveolin is a membrane protein, proposed to be a component of the striated
      coat covering the cytoplasmic surface of caveolae. To investigate the biochemical
      composition of the caveolar coat, we used our previous observation that VIP21
      caveolin is present in large complexes and insoluble in the detergents CHAPS or
      Triton X-114. The mild treatment of these insoluble structures with sodium
      dodecyl sulfate leads to the detection of high molecular mass complexes of
      approximately 200, 400, and 600 kDa. The 400-kDa complex purified to homogeneity
      from dog lung is shown to consist exclusive of the two isoforms of VIP21
      caveolin. Pulse-chase experiments indicate that the oligomers form early after
      the protein is synthesized in the endoplasmic reticulum (ER). VIP21-caveolin does
      indeed insert into the ER membrane through the classical translocation machinery.
      Its hydrophobic domain adopts an unusual loop configuration exposing the N- and C
      flanking regions to the cytoplasm. Similar high molecular mass complexes can be
      produced from the in vitro-synthesized VIP21-caveolin. The complex formation
      occurs only if VIP21-caveolin isoforms are properly inserted into the membrane;
      formation is cytosol-dependent and does not involve a vesicle fusion step. We
      propose that high molecular mass oligomers of VIP21-caveolin represent the basic
      units forming the caveolar coat. They are formed in the ER and later, between the
      ER and the plasma membrane, these oligomers could associate into larger detergent
      insoluble structures.

PMID- 7579701
TI  - Phosphorylation and localization of Kss1, a MAP kinase of the Saccharomyces
      cerevisiae pheromone response pathway.
AB  - Kss1 protein kinase, and the homologous Fus3 kinase, are required for pheromone
      signal transduction in Saccharomyces cerevisiae. In MATa haploids exposed to
      alpha-factor, Kss1 was rapidly phosphorylated on both Thr183 and Tyr185, and both
      sites were required for Kss1 function in vivo. De novo protein synthesis was
      required for sustained pheromone-induced phosphorylation of Kss1. Catalytically
      inactive Kss1 mutants displayed alpha-factor-induced phosphorylation on both
      residues, even in kss1 delta cells; hence, autophosphorylation is not obligatory
      for these modifications. In kss1 delta fus3 delta double mutants, Kss1
      phosphorylation was elevated even in the absence of pheromone; thus, cross
      phosphorylation by Fus3 is not responsible for Kss1 activation. In contrast,
      pheromone-induced Kss1 phosphorylation was eliminated in mutants deficient in two
      other protein kinases, Ste11 and Ste7. A dominant hyperactive allele of STE11
      caused a dramatic increase in the phosphorylation of Kss1, even in the absence of
      pheromone stimulation, but required Ste7 for this effect, suggesting an order of
      function: Ste11-->Ste7-->Kss1. When overproduced, Kss1 stimulated recovery from
      pheromone-imposed G1 arrest. Catalytic activity was essential for Kss1 function
      in signal transmission, but not for its recovery-promoting activity. Kss1 was
      found almost exclusively in the particulate material and its subcellular
      fractionation was unaffected by pheromone treatment. Indirect immunofluorescence
      demonstrated that Kss1 is concentrated in the nucleus and that its distribution
      is not altered detectably during signaling.

PMID- 7579704
TI  - The rho-GAP encoded by BEM2 regulates cytoskeletal structure in budding yeast.
AB  - Microfilaments are required for polarized growth and morphogenesis in
      Saccharomyces cerevisiae. To accomplish this, actin cables and patches are
      redistributed during the cell cycle to direct secretory components to appropriate
      sites for cell growth. A major component of actin cables is tropomyosin I,
      encoded by TPM1, that determines or stabilizes these structures. Disruption of
      TPM1 is not lethal but results in the loss of actin cables and confers a partial
      defect in polarized secretion. Using a synthetic lethal screen, we have
      identified seven mutations residing in six genes whose products are required in
      the absence of Tpm1p. Each mutant exhibited a morphological defect, suggesting a
      functional link to the actin cytoskeleton. Complementation cloning of one
      mutation revealed that it lies in BEM2, which encodes a GTPase-activating protein
      for the RHO1 product. bem2 mutations also show synthetic lethality with rho1 and
      mutations in certain other cytoskeletal genes (ACT1, MYO1, MYO2, and SAC6) but
      not with mutations in several noncytoskeletal genes. These data therefore provide
      a genetic link between the GAP encoded by BEM2 and the functional organization of
      microfilaments. In addition, we show that bem2 mutations confer benomyl
      sensitivity and have abnormal microtubule arrays, suggesting that the BEM2
      product may also be involved directly or indirectly in regulating microtubule
      function.

PMID- 7579705
TI  - Differential effects on cAMP on the MAP kinase cascade: evidence for a cAMP
      insensitive step that can bypass Raf-1.
AB  - Because cAMP exerts opposite effects on cell proliferation in different cell
      types, we undertook to study its effect on the mitogen-activated protein kinase
      (MAPK) pathway in three cell lines (Rat-1, Swiss-3T3, and COS-7) chosen for their
      different mitogenic responses to cAMP. We measured the effect of cAMP on MAPK,
      MEK, and Raf-1 activities after stimulation by agonists acting through a tyrosine
      kinase receptor (epidermal growth factor) or a G protein-coupled receptor
      (lysophosphatidic acid). In Rat-1 cells we found that cAMP strongly inhibited all
      three activities (MAPK, MEK, and Raf-1), in good agreement with its effect on
      cell proliferation in these cells. In Swiss-3T3 and COS-7 cells, on the contrary,
      cAMP did not inhibit epidermal growth factor- and lysophosphatidic acid-induced
      stimulation of MAPK and MEK activities, and even stimulated MAPK activity
      slightly on its own. Again these results are in good agreement with the
      proliferative effect of cAMP in Swiss-3T3 cells. Raf-1 activity on the hand, was
      inhibited by cAMP in Swiss-3T3 and COS-7 as it was in Rat-1 cells. This result
      indicates that signaling pathways in Swiss-3T3 and COS-7 cells can activate MEK
      and MAPK in a Raf-1-independent and cAMP-insensitive manner. Our results add to
      growing evidence for the existence of Ras- and/or Raf-1-independent pathways
      leading to MEK and MAPK activation.

PMID- 7579706
TI  - Dependence of stimulus-transcription coupling on phospholipase D in agonist
      stimulated pituitary cells.
AB  - Stimulation of phospholipase D activity is frequently observed during agonist
      activation of Ca(2+)-mobilizing receptors, but the cellular functions of this
      signaling pathway are not well defined. Pituitary gonadotrophs express Ca(2+)
      mobilizing receptors for gonadotropin-releasing hormone (GnRH) and endothelin
      (ET), activation of which stimulates luteinizing hormone secretion and transient
      expression of c-fos. In pituitary cells and alpha T3-1 gonadotrophs, GnRH action
      was associated with both initial and sustained diacylglycerol (DG) production,
      whereas ET-1 induced only a transient DG response. Also, phospholipase D
      activity, estimated by the production of phosphatidylethanol from
      phosphatidylcholine in the presence of ethanol, was stimulated by GnRH but not ET
      1. Such formation of phosphatidylethanol at the expense of phosphatidic acid (PA)
      during GnRH-induced activation of phospholipase D significantly reduced the
      production of PA, DG, and cytidine diphosphate diacylglycerol. Inhibition of PA
      phosphohydrolase activity by propranolol also decreased GnRH-induced DG
      production and, in contrast to ethanol, increased PA and cytidine diphosphate
      diacylglycerol levels. The fall in DG production caused by ethanol and
      propranolol was accompanied by inhibition of GnRH-induced c-fos expression,
      whereas agonist-induced luteinizing hormone release was not affected. In contrast
      to their inhibitory actions on GnRH-induced early gene expression, neither
      ethanol nor propranolol affected ET-1-induced c-fos expression, or GnRH- and ET-1
      induced inositol trisphosphate/Ca2+ signaling. These findings demonstrate that
      phospholipase D participates in stimulus-transcription but not stimulus-secretion
      coupling, and indicate that DG is the primary signal for this action.

PMID- 7579707
TI  - Domains required for CENP-C assembly at the kinetochore.
AB  - Chromosomes segregate at mitosis along microtubules attached to the kinetochore,
      an organelle that assembles at the centromere. Despite major advances in defining
      molecular components of the yeast segregation apparatus, including discrete
      centromere sequences and proteins of the kinetochore, relatively little is known
      of corresponding elements in more complex eukaryotes. We show here that human
      CENP-C, a human autoantigen previously localized to the kinetochore, assembles at
      centromeres of divergent species, and that the specificity of this targeting is
      maintained by an inherent destruction mechanism that prevents the accumulation of
      CENP-C and toxicity of mistargeted CENP-C. The N-terminus of CENP-C is not only
      required for CENP-C destruction but renders unstable proteins that otherwise
      possess long half-lives. The conserved targeting of CENP-C is underscored by the
      discovery of significant homology between regions of CENP-C and Mif2, a protein
      of Saccharomyces cerevisiae required for the correct segregation of chromosomes.
      Mutations in the Mif2 homology domain of CENP-C impair the ability of CENP-C to
      assemble at the kinetochore. Together, these data indicate that essential
      elements of the chromosome segregation apparatus are conserved in eukaryotes.

PMID- 7579708
TI  - Ezrin self-association involves binding of an N-terminal domain to a normally
      masked C-terminal domain that includes the F-actin binding site.
AB  - Ezrin is a membrane-cytoskeletal linking protein that is concentrated in actin
      rich surface structures. It is closely related to the microvillar proteins
      radixin and moesin and to the tumor suppressor merlin/schwannomin. Cell extracts
      contain ezrin dimers and ezrin-moesin heterodimers in addition to monomers.
      Truncated ezrin fusion proteins were assayed by blot overlay to determine which
      regions mediate self-association. Here we report that ezrin self-association
      occurs by head-to-tail joining of distinct N-terminal and C-terminal domains. It
      is likely that these domains, termed N- and C-ERMADs (ezrin-radixin-moesin
      association domain), are responsible for homotypic and heterotypic associations
      among ERM family members. The N-ERMAD of ezrin resided within amino acids 1-296;
      deletion of 10 additional residues resulted in loss of activity. The C-ERMAD was
      mapped to the last 107 amino acids of ezrin, residues 479-585. The two residues
      at the C-terminus were required for activity, and the region from 530-585 was
      insufficient. The C-ERMAD was masked in the native monomer. Exposure of this
      domain required unfolding ezrin with sodium dodecyl sulfate or expressing the
      domain as part of a truncated protein. Intermolecular association could not occur
      unless the C-ERMAD had been made accessible to its N-terminal partner. It can be
      inferred that dimerization in vivo requires an activation step that exposes this
      masked domain. The conformationally inaccessible C-terminal region included the F
      actin binding site, suggesting that this activity is likewise regulated by
      masking.

PMID- 7579709
TI  - Phosphorylated and dephosphorylated linker histone H1 reside in distinct
      chromatin domains in Tetrahymena macronuclei.
AB  - Phosphorylated and dephosphorylated isoforms of Tetrahymena macronuclear H1 were
      separated from each other by cation-exchange high performance liquid
      chromatography and used to generate a pairwise set of antisera that discriminate
      the phosphorylation state of this linker histone. Affinity-purified antibodies
      from each sera recognize appropriate H1 isoforms and stain macronuclei under
      appropriate physiological conditions. Immunogold localizations demonstrate that
      phosphorylated and dephosphorylated H1 localize nonrandomly in distinct
      subdomains of macronuclear chromatin. Dephosphorylated H1 is strongly enriched in
      the electron-dense chromatin bodies that punctuate macronuclear chromatin. In
      contrast, phosphorylated H1 isoforms, as well as an evolutionarily conserved
      H2A.F/Z-like variant (hv1) believed to function in the establishment of
      transcriptionally competent chromatin, are modestly enriched at the periphery of
      chromatin bodies and in the surrounding euchromatin. Using antibodies against
      TATA-binding protein, we show that transcriptionally active chromatin lies
      outside of the chromatin bodies in an area relatively devoid of H1. Antibodies
      against general core histones are more or less evenly distributed across these
      domains. Together, these data are consistent with a model in which
      phosphorylation of H1, perhaps in association with hv1, loosens the binding of H1
      in chromatin leading to chromatin decondensation as part of a first-step
      mechanism in gene activation. In contrast, our data support the view that
      dephosphorylation of this linker histone facilitates or stabilizes condensed,
      transcriptionally silent chromatin.

PMID- 7579710
TI  - InsP3-induced Ca2+ excitability of the endoplasmic reticulum.
AB  - Oscillations in intracellular Ca2+ can be induced by a variety of cellular
      signalling processes (Woods et al., 1986; Berridge 1988; Jacob et al., 1988) and
      appear to play a role in secretion (Stojilkovic et al., 1994), fertilization
      (Miyazaki et al., 1993), and smooth muscle contraction (Iino and Tsukioka, 1994).
      Recently, great progress has been made in understanding the mechanisms involved
      in a particular class of Ca2+ oscillation, associated with the second messenger
      inositol 1,4,5-trisphosphate (InsP3) (Berridge, 1993). Working in concert with
      intracellular Ca2+, InsP3 controls Ca2+ release via the InsP3 receptor in the
      endoplasmic reticulum (ER) (Berridge and Irvine, 1989). The IP3 receptor is
      regulated by its coagonists InsP3 and Ca2+, which both activate and inhibit Ca2+
      release (Finch et al., 1991; Bezprozvanny et al., 1991; De Young and Keizer,
      1992). These processes, together with the periodic activation of Ca2+ uptake into
      the ER, have been identified as key features in the mechanism of InsP3-induced
      Ca2+ oscillations in pituitary gonadotrophs (Li et al., 1994), Xenopus laevis
      oocytes (Lechleiter and Clapham, 1992; Atri et al., 1993), and other cell types
      (Keizer and De Young, 1993). Earlier discussions and models of InsP3-induced Ca2+
      oscillations focused on the nature and number of internal releasable pools of
      Ca2+ (Goldbeter et al., 1990; Swillens and Mercan, 1990; Somogyi and Stucki,
      1991), the importance of oscillations in InsP3 (Meyer and Stryer, 1988), and
      other issues not based on detailed experimental findings in specific cells types.

PMID- 7579712
TI  - Phorbol ester induces the rapid processing of cell surface heparin-binding EGF
      like growth factor: conversion from juxtacrine to paracrine growth factor
      activity.
AB  - Vero cell heparin-binding epidermal growth factor-like growth factor (HB-EGF) is
      synthesized as a 20- to 30-kDa membrane-anchored HB-EGF precursor (proHB-EGF).
      Localization and processing of proHB-EGF, both constitutive and 12-O
      tetradecanoylphorbol 13-acetate (TPA)-inducible, was examined in Vero cells
      overexpressing recombinant HB-EGF (Vero H cells). Flow cytometry and fluorescence
      immunostaining demonstrated that Vero cell proHB-EGF is cell surface-associated
      and localized at the interface of cell to cell contact. Cell surface
      biotinylation and immunoprecipitation detected a 20- to 30-kDa heterogeneous
      proHB-EGF species. Vero H cell surface proHB-EGF turned over constitutively with
      a half-life of 1.5 h. Some of the 20- to 30-kDa cell surface-associated proHB-EGF
      was processed and a 14-kDa species of bioactive HB-EGF was released slowly, but
      most of the proHB-EGF was internalized, displaying a diffuse immunofluorescent
      staining pattern and accumulation of proHB-EGF in endosomes. Addition of TPA
      induced a rapid processing of proHB-EGF at a Pro148-Val149 site with a half-life
      of 7min. The TPA effect was abrogated by the protein kinase C inhibitors,
      staurosporine and H7. Kinetic analysis showed that loss of cell surface proHB-EGF
      is maximal at 30 min after addition of TPA and that proHB-EGF is resynthesized
      and the initial cell surface levels are regained within 12-24 h. Loss of cell
      surface proHB-EGF was concomitant with appearance of 14- and 19-kDa soluble HB
      EGF species in conditioned medium. Vero H cell-associated proHB-EGF is a
      juxtacrine growth factor for EP170.7 cells in coculture. Processing of proHB-EGF
      resulted in loss of juxtacrine activity and a simultaneous increase in soluble HB
      EGF paracrine mitogenic activity. It was concluded that processing regulates HB
      EGF bioactivity by converting it from a cell-surface juxtacrine growth factor to
      a processed, released soluble paracrine growth factor.

PMID- 7579715
TI  - Therapeutic strategies for the management of carcinoma of the breast.

PMID- 7579711
TI  - Transformation and pp60v-src autophosphorylation correlate with SHC-GRB2 complex
      formation in rat and chicken cells expressing host-range and kinase-active,
      transformation-defective alleles of v-src.
AB  - The biochemical properties of several pp60v-src substrates believed to
      participate in src-mediated transformation were examined in cells expressing a
      kinase-active, transformation-defective v-src allele (v-src-F172 delta/Y416F) and
      its parental allele, v-src-F172 delta, a host-range--dependent allele that
      transforms chicken cells to a fusiform morphology, but does not transform rat
      cells. Because pp60v-src-F172 delta is dependent on autophosphorylation for
      transforming ability, these alleles provide a unique opportunity to examine the
      role of pp60v-src autophosphorylation in regulating substrate interactions.
      Increased pp125FAK tyrosine phosphorylation and high levels of pp60v-src
      associated phosphotidylinositol-3' kinase activity were detected specifically in
      chicken cells exhibiting round, refractile transformation but not in cells
      transformed to a fusiform morphology. Increased pp125FAK kinase activity, but not
      increased pp125FAK tyrosine-phosphorylation correlated with pp60v-src
      autophosphorylation and increased anchorage-independent growth. Thus, pp125FAK
      and PI3'K may participate in morphological transformation by v-src. Furthermore,
      association of phosphorylated SHC with the adapter GRB2 correlated with increased
      anchorage-independent growth (and autophosphorylation) in both rat and chicken
      cells independent of the morphological phenotype induced. Therefore, host-range
      dependence for transformation may be regulated through association of SHC with
      GRB2, thus implicating SHC as a crucial substrate for src-dependent
      transformation.

PMID- 7579716
TI  - Instruments of change.

PMID- 7579713
TI  - Polarity orientation and assembly process of microtubule bundles in nocodazole
      treated, MAP2c-transfected COS cells.
AB  - Microtubule bundles reminiscent of those found in neuronal processes are formed
      in fibroblasts and Sf9 cells that are transfected with the microtubule-associated
      proteins tau, MAP2, or MAP2c. To analyze the assembly process of these bundles
      and its relation to the microtubule polarity, we depolymerized the bundles formed
      in MAP2c-transfected COS cells using nocodazole, and observed the process of
      assembly of microtubule bundles after removal of the drug in cells microinjected
      with rhodamine-labeled tubulin. Within minutes of its removal, numerous short
      microtubule fragments were observed throughout the cytoplasm. These short
      fragments were randomly oriented and were already bundled. Somewhat longer, but
      still short bundles, were then found in the peripheral cytoplasm. These bundles
      became the primordium of the larger bundles, and gradually grew in length and
      width. The polarity orientation of microtubules in the reformed bundle as
      determined by "hook" procedure using electron microscope was uniform with the
      plus end distal to the cell nucleus. The results suggest that some mechanism(s)
      exists to orient the polarity of microtubules, which are not in direct continuity
      with the centrosome, during the formation of large bundles. The observed process
      presents a useful model system for studying the organization of microtubules that
      are not directly associated with the centrosomes, such as those observed in
      axons.

PMID- 7579717
TI  - Contemporary diagnostic approaches for nonpalpable carcinoma of the breast: the
      role of the radiologist.
AB  - Over the past 25 years the radiologist's role in the diagnosis of breast cancer
      has expanded from merely confirming the clinical suspicion of neoplasm to
      detecting occult nonpalpable tumors and now percutaneously obtaining tissue for
      histologic assessment. The cancer the radiologists discover is smaller in size
      and earlier in stage, allowing more conservative surgical approaches. This,
      coupled with adjuvant radiation therapy and chemotherapy, is producing newly
      demonstrated mortality reduction in this disease so feared by American women.

PMID- 7579714
TI  - Assembly and function of integrin receptors is dependent on opposing alpha and
      beta cytoplasmic domains.
AB  - The membrane proximal regions of integrin alpha and beta subunits are highly
      conserved in evolution. In particular, all integrin alpha subunits share the
      KXGFFKR sequence at the beginning of their cytoplasmic domains. Previous work has
      shown that this domain is important in integrin receptor assembly. Using chimeric
      integrin alpha and beta subunits, we show that the native cytoplasmic domains of
      both subunits must be present for efficient assembly. Most strikingly, chimeric
      alpha 1 and beta 1 subunits with reciprocally swapped intracellular domains
      dimerize selectively into collagen IV receptors expressed at high levels on the
      surface. However, these receptors, which bind ligand efficiently, are deficient
      in a variety of post-ligand binding events, including cytoskeletal association
      and induction of tyrosine phosphorylation. Furthermore, deletion of the distal
      alpha cytoplasmic domain in the swapped heterodimers leads to ligand-independent
      focal contact localization, which also occurs in wild-type subunits when the
      distal cytoplasmic domain is deleted. These results show that proper integrin
      assembly requires opposed alpha and beta cytoplasmic domains, and this opposition
      prevents ligand-independent focal contact localization. Our working hypothesis is
      that these two domains may associate during receptor assembly and provide the
      mechanism for integrin receptor latency.

PMID- 7579718
TI  - Management of in situ carcinoma of the breast: lobular and ductal origin.

PMID- 7579720
TI  - Adjuvant treatment of breast cancer.

PMID- 7579719
TI  - Breast conservation therapy in the management of invasive and in situ carcinoma.

PMID- 7579721
TI  - Locally advanced breast cancer: integration of multimodal concepts.

PMID- 7579723
TI  - Postmenopausal estrogen replacement therapy in the patient with breast carcinoma.

PMID- 7579724
TI  - Psychosocial needs of breast cancer patients in RI.

PMID- 7579725
TI  - Screening for non-insulin-dependent diabetes: the issues.

PMID- 7579722
TI  - Molecular biology of breast cancer: integration of cellular and molecular
      concepts into therapeutic strategies.

PMID- 7579727
TI  - Reference listings in cancer research.

PMID- 7579728
TI  - Retinoblastoma gene mutation in primary human renal cell carcinoma.
AB  - We searched for possible mutations in the E2F-binding region of retinoblastoma
      gene in primary human renal cell carcinomas, using polymerase chain reaction and
      single-strand conformational polymorphism analysis of RNA. Retinoblastoma gene
      mutation was detected in 1 of 21 cases (5%). DNA sequencing of the polymerase
      chain reaction product verified that this case had a 6-base deletion at the
      beginning of exon 8. Our findings suggest that mutation of the retinoblastoma
      gene is involved in only a subgroup of sporadic human renal cell carcinomas.

PMID- 7579726
TI  - DNA topoisomerase II expression, stability, and phosphorylation in two VM-26
      resistant human leukemic CEM sublines.
AB  - We have examined features of DNA topoisomerase II (topo II) isoforms in human
      leukemic CCRF-CEM cells and two teniposide-resistant sublines, CEM/VM-1 and
      CEM/VM-1-5. They are about 40- to 50-fold and 150- to > 400-fold resistant to
      teniposide, respectively, and have increased levels of cross-resistance to other
      complex-stabilizing topo II inhibitors. Topo II activity in these lines is
      reduced in proportion to their resistance. However, both sublines carry two
      identical point mutations in topo II alpha cDNA that have recently been found to
      confer resistance to etoposide and m-AMSA in transfected yeast cells. Although
      these data provide a strong molecular basis for this type of multidrug
      resistance, these findings alone cannot explain the increased level of resistance
      and cross-resistance, and the further decreased cellular topo II activities in
      the most resistant CEM/VM-1-5 cells compared to CEM/VM-1 cells. In this study we
      found that (1) topo II beta is not expressed in CEM/VM-1-5 cells; (2) a 160-kDa
      protein was consistently detected and coimmunoprecipatated only in nuclear
      extracts of CEM cells; (3) when nuclear extracts from all three cell lines were
      incubated at 37 degrees C, an immunoreactive band of 140-kDa appeared by 60-90
      min only in samples of CEM cells, not in those of CEM/VM-1 and CEM/VM-1-5 cells;
      and (4) the in vivo phosphorylation level of topo II alpha protein was decreased
      > or = 2-fold in both resistant cell lines, compared to that of CEM cells. Thus,
      cell lines selected for the altered topo II-associated multidrug resistance
      phenotype may contain multiple alterations in both topo II isoforms.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579729
TI  - Possible correlation between ormaplatin biotransformations and neurotoxicity.
AB  - Clinical development of ormaplatin has been delayed because of neurotoxicity that
      was not predictable on the basis of patient characteristics, total cumulative
      dose, or plasma pharmacokinetics. We report a detailed comparison of the plasma
      biotransformations of ormaplatin in two patients at the 123 mg/m2-dose
      administered as a 1-h infusion every 4 weeks. One of these patients developed
      neurotoxicity after 2 cycles (total cumulative dose = 246 mg/kg), while the other
      patient showed no symptoms of neurotoxicity through 2 cycles. The maximum plasma
      concentration and area under the curve for ultrafilterable platinum were greater
      for the patient that did not develop neurotoxicity. However, both maximum plasma
      concentration and area under the curve were greater for dichloro(d,l-trans)1,2
      diaminocyclohexanedichloroplatinum(II), the major active biotransformation
      product of ormaplatin, in the patient that developed neurotoxicity. In addition,
      analysis of plasma biotransformation products suggested that the initial plasma
      concentrations of ormaplatin were also greater in the patient that developed
      neurotoxicity. These data suggest that analysis of individual plasma
      biotransformation products may be useful in predicting toxicity of platinum
      anticancer agents and should be included in future phase I studies.

PMID- 7579730
TI  - Contrasting patterns of DNA fragmentation induced by thymidylate synthase
      inhibitors, ZD1694 and AG-331.
AB  - The patterns of DNA fragmentation were evaluated following a brief exposure (2 h)
      of the human ileocecal adenocarcinoma cell line, HCT-8, to several specific
      thymidylate synthase inhibitors, a quinazoline (ZD1694) and benz[cd]indole
      containing molecule (AG-331). The magnitude and size of DNA fragmentation induced
      by the two agents were assessed by alkaline elution for DNA single-strand breaks
      (ssbs), and by pulsed- and constant-field gel electrophoresis for DNA double
      strand breaks (dsbs). Both agents induced dose-dependent DNA dsbs. While AG-331
      induced ssbs and dsbs only in nascent DNA, ZD1694 affected both genomic and
      nascent DNA. The fragments of newly synthesized and genomic DNA, estimated by
      pulsed-field gel electrophoresis assay, were associated with the bands in the
      range of 0.05 to 1.1 and 1.1 to 5.7 megabases, respectively. 5-fluoro-2'
      deoxyuridine (FdUrd), like ZD1694, produced both mature and nascent DNA
      fragmentation, whereas only nascent DNA breakage induced by 5-fluorouracil (FUra)
      was detected, similar to AG-331. The induction of both mature and nascent DNA
      fragmentation by ZD1694 and FdUrd appears to correlate with the higher, but
      similar, potency of these agents. Aphidicolin, a DNA polymerase inhibitor,
      protects from DNA dsbs and cytotoxicity by ZD1694 and AG-331. These observations
      suggest that replicative DNA synthesis is an important factor in ZD1694- and AG
      331-induced DNA fragmentation and, subsequently, cell growth arrest. The results
      indicate that although the new antimetabolites investigated herein were developed
      and extensively evaluated as specific and potent thymidylate synthase inhibitors,
      DNA damage appears to be an important additional determinant of drug
      effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579731
TI  - Altered topoisomerase I expression in two subclones of human CEM leukemia
      selected for resistance to camptothecin.
AB  - Two camptothecin-resistant variants of the CEM human leukemia cell line were
      developed by stepwise selection in camptothecin (CPT) in vitro. The two lines,
      named CEM/C1 and CEM/C2, were found to be approximately 31- and 970-fold less
      sensitive to CPT, respectively, than the CEM parental line and variably cross
      resistant to the CPT analogs 9-amino-CPT, 10,11-methylenedioxy-CPT, and
      topotecan. Levels of DNA-protein complex formation resulting from cell exposure
      to CPT were found to be progressively reduced in the CPT-resistant cells, despite
      equivalent CPT accumulation in the drug-sensitive and -resistant cells. Nuclear
      extracts (1.0 M NaCl) prepared from the CEM/C1 and CEM/C2 lines contained 1.5- to
      2-fold less DNA topoisomerase I catalytic activity per microgram of protein than
      did extracts from the drug-sensitive CEM line, in association with altered
      sensitivity of the enzyme in the CEM/C1 and CEM/C2 extracts to the inhibitory
      activity of CPT. Only minor differences were noted in the CPT IC50s for the
      topoisomerase I activity in extracts from the two CPT-resistant cell lines,
      however, despite the marked differences in cellular sensitivity to CPT. There
      were notable differences in the level of CPT-induced cleavage of DNA
      oligonucleotides by topoisomerase I in nuclear extracts from CEM cells compared
      with the drug-resistant cell extracts, with very little oligonucleotide cleavage
      induced by enzyme in either drug-resistant cell type, despite the use of very
      high (100 microM) CPT concentrations. The alterations in topoisomerase I
      catalytic activity were associated with reduced cellular levels of both
      immunoreactive topoisomerase I protein (representing 59 +/- 19% [CEM/C1] and 49
      +/- 12% [CEM/C2] of that in CEM, respectively) and mRNA.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7579732
TI  - Role of membrane-associated folate binding protein in the cytotoxicity of
      antifolates in KB, IGROV1, and L1210A cells.
AB  - Based on differential levels of membrane-associated folate binding protein (mFBP)
      expression, murine L1210 leukemia, human KB epidermoid carcinoma, and human
      IGROV1 ovarian carcinoma cells maintained under low (physiological) folate
      conditions (2 nM folinic acid) were used as model systems to investigate the
      potential role of mFBP in antifolate transport. In addition, L1210 parental cells
      were compared to a subline, L1210A, expressing high levels of mFBP and defective
      reduced folate carrier. Antifolates for which KB-derived mFBP has high affinity
      (5, 10-dideazatetrahydrofolic acid [DDATHF] and homo-DDATHF [0.24 and 0.78
      respectively relative to folic acid]) and low affinity (methotrexate [0.002])
      were chosen for this study. Protection against DDATHF/homo-DDATHF induced
      cytotoxicity was achieved preferentially by folic acid compared to folinic acid
      in IGROV1 and L1210A cells. In IGROV1 cells, cytotoxicity IC50s were increased 18
      and 5.5-fold for DDATHF and homo-DDATHF respectively by 20 nM folic acid.
      Moreover, greater protection was observed in L1210A cells, where IC50s were
      increased 354- and 80-fold for these same compounds by 20 nM folic acid. Similar
      protection was not observed in KB cells, suggesting that KB mFBP was not
      functional in DDATHF transport. Although mFBP expression may be an important
      determinant in the cytotoxicity of antifolates for certain tumor cells, our data
      demonstrate a lack of correlation between levels of mFBP and function of mFBP for
      DDATHF transport in the models studied.

PMID- 7579733
TI  - Normocalcemic hyperparathyroidism associated with relatively low 1:25 vitamin D
      levels post-renal transplant can be successfully treated with oral calcitriol.
AB  - Since endogenous 1:25 vitamin D (1:25VD) is principally involved with involution
      of secondary hyperparathyroidism post-renal transplant we correlated 1:25VD
      levels with intact PTH in 82 random patients with a serum creatinine of < 2 mg/dl
      and with normal hepatic function. All patients studied were normocalcemic with
      normal phosphorus and received azathioprine, cyclosporin A and prednisone. Of
      considerable interest, of the 42 patients studied after 2 years post-transplant,
      there were 8 (19%) patients with intact PTH of more than twice the upper limit of
      normal (normal 10-65 pg/ml) and other 15 (36%) with PTH levels above normal.
      Secondly, in no patient did we see 1:25VD above normal (normal 15-60 pg/ml)
      despite levels of PTH of > 200 pg/ml. Of concern, 20% of 73 patients had 1:25VD
      deficiency (< 15 pg/ml). This may not have been previously appreciated because of
      the number of patients studied. Like previous investigators, we failed to
      understand why 1:25VD levels were relatively low. There was no correlation
      between 1:25VD and serum creatinine. Of 25 patients with a serum creatinine of
      1.4 or less, there were 10 patients (40%) with 1:25VD of less than 20 pg/ml.
      Since persistently high PTH can contribute to bone demineralization, which is not
      uncommon post-transplant, we treated 8 patients with small doses of oral 1:25VD
      (rocaltrol). In less than 6 months PTH levels returned to normal in 7 of the 8
      patients. The current studies clearly indicate that asymptomatic
      hyperparathyroidism is common even after 2 years post-renal transplant.
      Monitoring for PTH and 1:25VD will help prevent bone disease post-transplant now
      that rocaltrol is available.

PMID- 7579734
TI  - An analysis of predictors of long-term cadaveric renal allograft survival.
AB  - To determine factors predictive of long-term graft function in patients treated
      prophylactically with an antilymphocyte antibody, 670 first cadaveric adult renal
      transplant procedures performed between 1985 and 1991 were reviewed. The
      actuarial 1- and 5-year patient survival in this group was 95% and 87%
      respectively, and graft survival was 84% and 70% respectively. The final analysis
      was based on a study group of 635 patients which excluded 28 patients who lost
      grafts to early technical failures and 8 patients who were not induced with an
      antilymphocyte preparation. Multivariate analysis showed that 5-year graft
      survival was lower in patients with delayed graft function (p = 0.0001), in those
      who had an acute rejection episode in the first 6 months post-transplant (p =
      0.0001), recipients greater than 55 years of age at the time of transplant (p =
      0.0001), in patients who were highly sensitized at the time of transplant (p =
      0.0331) and, finally, in those who received a graft from an older donor (p =
      0.044). The 209 patients with delayed graft function had a 16% lower long-term
      graft survival than 425 patients with early graft function (62% vs. 78%
      respectively at 5 years). One or more rejection episodes in the first 6 months
      post-transplant (329 patients) reduced long-term graft survival by 13% compared
      to those who did not have a rejection episode (67% vs. 80% respectively at 5
      years).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579735
TI  - Post-transplant diabetes mellitus and methylprednisolone pharmacokinetics in
      African-American and Caucasian renal transplant recipients.
AB  - Post-transplant diabetes among renal transplant recipients is more prevalent in
      the African-American population. However, it is unknown if methylprednisolone (a
      commonly prescribed glucocorticoid in transplant patients) pharmacokinetics is
      altered among African-American renal allograft recipients compared to Caucasian
      counterparts. Therefore, the objectives of this study were to identify the
      occurrence of post-transplant diabetes in our clinic population and to
      characterize the pharmacokinetics of methylprednisolone among our African
      American and Caucasian renal transplant recipients. A retrospective chart survey
      was done on African-American and Caucasian recipients with stable renal function
      and no history of diabetes pre-transplantation in order to characterize the
      occurrence of post-transplant diabetes in our clinical population. The survey was
      conducted from January 1985 to January 1992 in recipients with graft survival of
      at least 3 months. Post-transplant diabetes was defined as two fasting glucose
      serum concentrations greater than 140 mg/dl or one random serum glucose
      concentration greater than 200 mg/dl which was confirmed by a fasting serum
      glucose value greater than 140 mg/dl and a 2 hour post-prandial greater than 200
      mg/dl. A 24-hour pharmacokinetic evaluation was conducted in a sub-group of
      African-American and Caucasian patients after intravenous administration of
      methylprednisolone. Over the survey period, 75 renal transplants (30 females; 45
      males) were performed and 50 of these transplant recipients (24 females; 26
      males) were not diabetic prior to the allograft placement. Of these 50 patients,
      22 males and 17 females fulfilled the inclusion criteria established for the
      retrospective survey.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579738
TI  - Hyperaluminemia associated with liver transplantation and acute renal failure.
AB  - Iatrogenic aluminium toxicity is reported in a patient who underwent an
      orthotopic liver transplant and who had concomitant renal failure requiring
      hemodialysis. Following transplantation the patient developed a metabolic
      encephalopathy with only mildly elevated blood ammonia concentrations. During the
      period following transplantation the patient received massive infusions of
      albumin and was on oral feeding (vivonexten), both of which contained aluminium,
      as did the dialysis fluid. Hyperaluminemia and profoundly elevated liver tissue
      aluminium concentrations were observed. Treatment with desferrioxamine, a
      trivalent ion chelator, decreased the plasma aluminium concentrations with an
      improvement in the patient's mental status.

PMID- 7579737
TI  - Hepatic venous catheterization in patients undergoing positive end-expiratory
      pressure ventilation after OLT: technique and clinical impact.
AB  - The objective of this study was to determine the feasibility and clinical impact
      of hepatic venous oxygenation monitoring in patients undergoing positive end
      expiratory pressure (PEEP) ventilation after OLT. The design comprised a
      prospective study using repeated-measures design, within an intensive-care unit
      for liver-transplanted patients in a university hospital. Sixteen consecutive
      adult patients undergoing orthotopic liver transplantation were enrolled.
      Postoperatively, a fiber-optic pulmonary artery catheter was inserted into the
      right hepatic vein. Patients were submitted to controlled ventilation with three
      different levels of end-expiratory pressure (PEEP): 0, 5 and 10 mbar.
      Hemodynamics, hepatic venous pressure, mixed venous (SvO2) and hepatic venous
      oxygenation (SvhO2) were measured. The average time required for hepatic venous
      catheterization was 2.9 +/- 1.2 min; serious complications were not observed.
      PEEP 5 mbar did not alter hemodynamics and SvhO2; PEEP 10 mbar significantly
      reduced cardiac index, SvO2 and widened arteriovenous content difference (p <
      0.05). The mean difference between SvO2 and SvhO2 was 6.3 +/- 6.0% and did not
      change during PEEP ventilation. A significantly positive relationship was
      observed between SvO2 and SvhO2 (r = 0.91, p < 0.05). Hepatic venous
      catheterization appeared to be practical and could be utilized to evaluate the
      effects of therapeutic interventions on the transplanted liver. However, the
      small number of patients studied will not allow the assessment of any risk
      benefit ratio of the technique investigated. Low levels of PEEP provided
      hemodynamic stability and did not alter hepatic oxygen supply-demand
      ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579736
TI  - Hemoconcentration prior to serology testing in hemodiluted cadaver bone and
      tissue donors.
AB  - Concern about false negative serology tests for infectious diseases in
      hemodiluted cadaver donors resulted in issuance of new regulations and guidelines
      from the FDA and CDC. Bone or tissue from donors receiving > or = 4 units of
      blood, blood products, colloids or crystalloids within 48 h of sampling must be
      quarantined unless: (a) a pretransfusion serum is available; or (b) an adequate
      algorithm is employed to ensure hemodilution is insufficient to alter test
      results, i.e. cause false negatives. Left undefined in these regulations is, what
      is an adequate algorithm and what amount of hemodilution would cause false
      negatives. A pretransfusion sample was not available for about 20% of our donors
      and many had incomplete infusion histories. We used the unambiguous quantitation
      of serum albumin and total protein to define hemodilution and, if present,
      hemoconcentration of sera by ultrafiltration to normal protein levels prior to
      serology testing. Control experiments showed excellent correlation between serum
      dilution and protein concentration (r > 0.99) and a quantitative recovery of 96.9
      +/- 1.4% upon hemoconcentration. Known positive sera (CMV-Ab; HTLV-1Ab; HIV
      1,2Ab; HBsAb; HCV-Ab; HBsAg) were spiked into normal sera and diluted up to
      1:2000, well beyond detectable levels. A qualitative recovery of 100% and a
      quantitative recovery of 97.6 +/- 7.5% of antibody or antigen reactivity was
      achieved upon hemoconcentration and retesting. In two studies, 14% (30/210) and
      43% (23/54) of cadaver donors had serum proteins below normal limits and their
      sera was hemoconcentrated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579739
TI  - Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant
      patients.
AB  - We hereby report our experience with an index case of a pediatric liver
      transplant patient in whom FK506 administration was associated with the
      development of proximal renal tubular acidosis (RTA), as well the prevalence of
      acidosis and renal dysfunction in all pediatric liver transplant patients in our
      institution followed long term during a 6-year period. Data were grouped
      according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or
      CsA with conversion to FK506. A 23-month-old female treated with FK506 after
      orthotopic liver transplantation (OLT) performed 15 months earlier presented with
      a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the
      acidosis did not improve following correction of her hydration status,
      administration of oral bicarbonate was effective. Discontinuation of this therapy
      resulted in acidosis. Since other indirect measurements of renal tubular function
      were normal, the patient was judged to have an isolated proximal RTA. In our
      group of pediatric liver transplant patients converted from CsA to FK506, FK506
      administration was associated with a decline in serum bicarbonate (19 +/- 1 vs.
      16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine
      differed between the two groups. The number of rejection episodes/patient/month
      was comparable, allowing clinically relevant comparison of relative drug
      nephrotoxicities. We conclude that proximal RTA may be a relatively common
      treatable complication of FK506 administration in children.

PMID- 7579740
TI  - Attitudes of commercial renal transplant recipients toward renal transplantation
      in India.
AB  - Renal transplantation offers patients with end-stage renal disease the best
      opportunity for rehabilitation and long-term survival. However, there is a
      critical shortage of transplantable kidneys worldwide. This plays well into the
      hands of transplanters and entrepreneurs involved in commercial renal
      transplantation, particularly in India. This practice has been condemned by all
      transplant societies. In our fight against rampant commercialism in renal
      transplantation, we sought to describe feelings of patients who had received
      transplants in India, and the difficulties they faced during their stay there.
      The results show that the two reasons that motivated patients to go to India were
      lack of living-related donors and the need for prompt transplant. More than half
      of the patients did not meet their donors. Their experience, however, has been
      largely positive except for some negative feelings toward the broker and the
      standard of hospital hygiene. The total cost of the transplant was far less than
      that in the West but, despite that, some patients felt financially exploited.
      Communication with them was poor, as most patients did not get adequate
      pretransplant education and were not informed of possible complications including
      rejection and graft loss. Furthermore, almost half of the patients were not given
      medical reports. These results substantiate the impression that CRT in India does
      not conform to the high standards of renal transplant medicine.

PMID- 7579741
TI  - Alternate-day prednisone in the maintenance immunosuppressive therapy after
      orthotopic liver transplantation.
AB  - Glucocorticoids have been an important part of maintenance immunosuppressive
      therapy following orthotopic liver transplantation (OLT). However, long-term
      daily glucocorticoid use is associated with a high incidence of unpleasant side
      effects. In an effort to minimize side effects while maintaining adequate
      immunosuppression, we have treated 48 adult patients with low dose alternate-day
      prednisone, 15 mg q.o.d. Pre-OLT diagnoses included primary biliary cirrhosis (16
      patients), alcoholic liver disease (8 patients), sclerosing cholangitis (8
      patients), cryptogenic cirrhosis and/or non-A, non-B hepatitis (11 patients),
      acute hepatic failure (3 patients), and hepatocellular carcinoma and bile duct
      carcinoma (1 patient each). Conversion to alternate-day prednisone was attempted
      when patients were clinically stable and the daily prednisone dose was 15 mg. The
      average interval between OLT and beginning of the conversion to alternate-day
      prednisone was 38 weeks. The mean time for conversion to alternate-day prednisone
      was 35 weeks, but decreased as more experience was gained. The mean follow-up was
      106 weeks. Cushingoid side effects diminished in all. In 47 of the 48 patients,
      there were no clinical laboratory or histologic changes suggestive of rejection
      after the initiation of alternate-day prednisone. A single episode of rejection
      occurred during the taper. This episode responded promptly to increased
      glucocorticoid therapy, and the patient was easily converted to alternate-day
      prednisone at a later date. There was no increase in concurrent
      immunosuppressives dosage after the conversion. Alternate-day prednisone is
      effective and safe for chronic immunosuppression after OLT in patients receiving
      cyclosporine and azathioprine.

PMID- 7579743
TI  - Induction therapy with cyclosporine without cytolytic agents results in a low
      incidence of acute rejection without significant renal impairment in heart
      transplant patients.
AB  - Since 1989, the immunosuppressive regimen used in all heart transplant patients
      at our center has consisted of (i) cyclosporine induction therapy (pretransplant
      p.o. 2-6 mg/kg depending on serum creatinine level, with immediate post
      transplant i.v. therapy at 1-3 mg/h until p.o. therapy alone maintains a whole
      blood trough level of 300 ng/ml by RIA); (ii) azathioprine (2.5 mg/kg/d
      i.v./p.o.); (iii) methylprednisolone i.v. for 24 h and then prednisone p.o. at 1
      mg/kg/d, tapering to 0.1 mg/kg/d at 1 yr. No prophylactic cytolytic agents (ALG,
      OKT3) were given. One hundred consecutive patients have been followed for periods
      of 4-56 months (mean 27 months). The incidence of acute rejection requiring
      increased therapy was 24%, with only 7% requiring i.v. steroids, 2 of whom (2%)
      also required ALG and/or OKT3, and with 17% requiring increased oral
      immunosuppression alone. Mean creatinine levels (mg/dl) were 1.3 pretransplant,
      1.4 on d 7, 1.5 at 30 d, and 1.8 after 2 yr. Only 1 patient required temporary
      hemodialysis. Survival was 98% at 30 d, 94% at 1 yr, and 92% at 2 yr. We conclude
      that cyclosporine induction therapy with steroids and azathioprine without any
      cytolytic agent results in a low incidence of acute rejection without
      jeopardizing renal function.

PMID- 7579742
TI  - Evaluation of an organ-donor-card campaign in Sweden.
AB  - One of the aims of this study was to evaluate an information campaign carried out
      in three geographical areas of Sweden in the winter of 1992-93. The campaign was
      intended to increase public awareness of organ donation and to increase the
      signing of donor cards. Another objective was to test the effects of different
      kinds of information. These were: A) an extensive "package" of information
      including training of key groups, lecturing at meetings and exhibitions, and
      advertisements of donor cards: B) a brochure to households including two donor
      cards; and C) a combination of A and B. Yet another aim was to reassess public
      opinion on transplantation issues, which had been surveyed before in 1987, 1988,
      and 1990. Random samples of the population in three campaign areas and a control
      sample were surveyed before and after the campaign, altogether 5600 persons. The
      average response rate was 69% (1992) and 68% (1993). In the two areas where the
      brochure had been distributed to the households, the rate of donor card holders
      had more than doubled (from 3% and 5% to 13% and 12%). In the two areas where the
      brochure had not been distributed, the rate was unchanged (5%). In the "brochure
      areas" also a somewhat larger number of people had informed their relatives about
      their decisions, compared with people in the other areas. In all campaign areas
      considerably more people were aware of the cards than in the control area. No
      attitude changes could be shown in any area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579745
TI  - Gastrointestinal tuberculosis in renal transplantation: a case report and review.
AB  - The pattern of tuberculosis has changed and in recent years: extrapulmonary
      tuberculosis has become more common, especially in immuno-compromised
      individuals. A case of primary intestinal tuberculosis in a patient with kidney
      transplant is reported. The patient presented with persistent fever and right
      sided abdominal pain. Histopathology of colonic tissue showed granulomatous
      inflammation containing acid fast bacilli, and culture of the tissue grew
      Mycobacterium tuberculosis. Clinical improvement occurred after institution of
      appropriate anti-tubercular treatment.

PMID- 7579744
TI  - Post-transplant hyperlipidemia: risk factors and response to dietary modification
      and gemfibrozil therapy.
AB  - A retrospective chart analysis of 200 consecutive, cyclosporine-treated, renal
      allograft recipients, transplanted between January 1988 and June 1992, was
      conducted to determine the incidence of and the etiologic variables for post
      transplant hypercholesterolemia. In addition, the effectiveness of dietary
      intervention alone or in combination with gemfibrozil (600 mg b.i.d.), in post
      transplant hypercholesterolemia was evaluated. Hypercholesterolemia (> or = 240
      mg/dl on two separate determinations, while on maintenance immunosuppression) was
      present in 138 patients (Group A-69%). When compared to the remaining 62 patients
      without hypercholesterolemia (Group B-31%), there were no differences in mean
      age, body weight at transplantation, race, incidence of overt diabetes, systolic
      and diastolic blood pressure, or serial serum creatinine, albumin, and
      cyclosporine levels between these groups. Post-transplant hypercholesterolemia
      was significantly more prevalent in females, in recipients with higher baseline
      serum total cholesterol levels (mean +/- SEM, Group A = 229.0 +/- 5.0 vs. Group B
      = 192.0 +/- 6.1 mg/dl, p < 0.001), and in recipients with an elevated fasting
      blood glucose at 1 year post-transplant (Group A = 150.5 +/- 10.5 vs. Group B =
      105.2 +/- 10.7 mg/dl, p < 0.05). In all patients with hypercholesterolemia, a
      hypocaloric low fat and low cholesterol (< 300 mg/day) diet was initiated at a
      mean of 0.59 +/- 0.06 years after transplantation with grading of dietary
      compliance at each follow-up visit (Grade 1, < 300 mg cholesterol; Grade 2, 300
      500 mg cholesterol; Grade 3, > 500 mg cholesterol intake in 24 hours).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579746
TI  - Assessment of intracranial primary collaterals using transcranial color-coded
      real-time sonography.
AB  - Transcranial color-coded sonography (TCCS) was used to assess primary willisian
      collaterals in 100 patients with extracranial internal carotid artery (ICA)
      stenosis. Their importance was determined during carotid endarterectomy (CEA) by
      transcranial Doppler measurement of blood flow velocity in the ipsilateral middle
      cerebral artery (MCAV) before and after carotid clamping. All patients had
      unilateral ICA disease of at least 60% stenosis. Twenty-nine ICAs (14.5%) were
      occluded, 70 vessels (35%) were stenosed by 80 to 99%, 43 vessels (21.5%) were
      stenosed by 60 to 79%, and 53 ICAs had stenosis of less than 60%. Temporal
      hyperostosis precluded TCCS in 15 patients (15%). Anterior cerebral/communicating
      artery collaterals were detected in 40 patients (49%) and posterior
      cerebral/communicating artery collaterals were detected in 22 patients (27%). No
      patients with ICA stenosis of less than 80% had established collateral pathways.
      Patients with willisian collaterals showed higher postclamp MCAVs as a proportion
      of the preclamp value during CEA (72% [62-81]; median with 95% confidence
      interval) than did those without primary collaterals (46% [34-58], p = 0.02).
      TCCS allows noninvasive assessment of intracranial primary collaterals whose
      functional importance is recognized during abrupt hemodynamic challenge. It may
      determine which patients are at greatest risk of ischemia during cerebral
      revascularization.

PMID- 7579747
TI  - False evidence of carotid stenosis on magnetic resonance angiography caused by
      surgical clips.
AB  - Patients with transient ischemic attacks are increasingly studied with magnetic
      resonance angiography, allowing noninvasive evaluation of both the intracranial
      and the extracranial vessels. Described here are 3 patients who after
      endarterectomies presented with transient ischemic attacks and in whom magnetic
      resonance angiography with a two-dimensional time-of-flight pulse sequence showed
      a false-positive arterial stenosis, as documented by transfemoral carotid
      angiography. The pseudostenosis was believed to be artifactually caused by
      operative clips. Results of magnetic resonance angiography should be interpreted
      with caution in patients with previous neck surgery.

PMID- 7579748
TI  - Changes in cerebral blood flow as monitored by transcranial Doppler during
      voluntary hyperventilation and their effect on the electroencephalogram.
AB  - Hyperventilation results in a fall in carbon dioxide concentration, a fall in
      cerebral blood flow, and slowing of activity on the electroencephalogram. The
      temporal relationship and duration of these responses are uncertain, and were
      investigated using simultaneous monitoring of cerebral blood flow velocity and of
      the electroencephalograph, with end-tidal carbon dioxide monitoring. Sixteen
      patients and 9 normal volunteers were studied. Cerebral blood flow velocity in
      the middle cerebral artery was measured using transcranial Doppler sonography
      during 3 minutes of hyperventilation and during a 3-minute recovery period.
      Electroencephalographic recordings were rated by both visual score and
      measurement of the dominant posterior frequency. End-tidal expired carbon dioxide
      tension was monitored during the same hyperventilation protocol in the
      volunteers. Flow velocity fell rapidly during active hyperventilation.
      Electroencephalographic slowing closely correlated with the decrease in flow
      velocity (r = 0.86), but lagged behind it. In healthy volunteers capnographic
      records showed a very tight coupling between end-tidal carbon dioxide
      concentration and flow velocity (r = 0.94). Three minutes after hyperventilation,
      carbon dioxide concentration, cerebral blood flow velocity, and
      electroencephalographic activity were still not back to the resting state. The
      fall in both cerebral blood flow velocity and carbon dioxide concentration are
      related to but precede electroencephalographic slowing. The abnormalities persist
      for at least 3 minutes after hyperventilation and this must be taken into account
      in clinical electroencephalography. Transcranial Doppler sonography is well
      suited to monitoring short-term changes in the cerebral circulation.

PMID- 7579749
TI  - Modification of low-frequency spontaneous oscillations in blood flow velocity in
      large- and small-artery disease.
AB  - During a 30-minute period, the blood flow velocity of both middle cerebral
      arteries (MCAs) was measured bilaterally in 27 patients with obstructive carotid
      disease (n = 18, large-artery disease) or subcortical vascular encephalopathy (n
      = 9, small-artery disease) and in control subjects of similar age and sex
      distribution (n = 14). To identify low-frequency spontaneous oscillations
      (LFSOs), MCA envelope curves were Fourier transformed with filter application to
      select low-frequency spectra (0.01-0.05, 0.05-0.15, 0.15-0.50 Hz). To measure the
      extent of LFSO amplitudes, a coefficient of variation (CoV) was calculated. In
      addition, a coefficient of correlation (CoC) was calculated to assess LFSO
      bilateral synchronicity. Normal ranges for CoV (mean = 5.38 +/- 1.82%) and CoC
      (mean = 0.91 +/- 0.06) were established in control subjects. In patients with
      large-artery disease, a significant CoV reduction was observed ipsilateral to the
      carotid lesion (CoV mean = 3.91 +/- 1.10%; p < 0.05, Wilcoxon's test) with a
      contralateral compensatory increase (CoV mean = 5.68 +/- 1.79%). In addition, a
      significant desynchronization of LFSOs was found in patients with large-artery
      disease (CoC = 0.39 +/- 0.35, p < 0.05). This was less obvious in patients with
      small-artery disease, who demonstrated a marked bilateral reduction of LFSO
      activity (CoV mean = 3.60 +/- 0.71%, p < 0.05) and CoC values.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7579750
TI  - Basal ganglia and frontal lobe glucose metabolism. A reproducibility positron
      emission tomography study.
AB  - Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) is
      frequently used to study the metabolic correlates of movement and mental
      disorders. These studies generally focus on changes in the frontal cortex and the
      basal ganglia. The reproducibility of glucose metabolism estimates in these
      structures was tested in 13 normal subjects studied at rest using a standard and
      simple protocol. A reproducible dorsoventral metabolic gradient was demonstrated
      in the frontal cortex. Such a gradient was not present in the basal ganglia when
      the upper region of interest in the caudate nucleus, where the lower metabolic
      rate of glucose was probably attributable to partial volume effects, was not
      considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% in
      the frontal cortex and by 6.8 to 14.7% in the basal ganglia. Variations in
      normalized values in the basal ganglia ranged from 4.0 to 8.6%. The number of
      subjects required to detect statistical differences in group comparison or in
      test-retest studies was calculated for different anticipated levels of change.
      With the variability detected in this experiment, less than 10 subjects were
      expected to be sufficient to detect a 15% change in most regions and in both
      types of studies.

PMID- 7579751
TI  - Functional caudate imaging in symptomatic Huntington's disease: positron emission
      tomography versus single-photon emission computed tomography.
AB  - Functional neuroimaging with positron emission tomography previously demonstrated
      reduced caudate glucose metabolism in virtually all symptomatic patients with
      Huntington's disease (HD). Single-photon emission computed tomography studies of
      brain blood flow also have shown caudate abnormalities in patients with HD. The
      present study compared these two functional imaging modalities in 6 patients with
      HD who had been symptomatic for fewer than 5 years. All patients had
      significantly impaired caudate-thalamus and caudate-whole-slice glucose
      metabolism ratios as measured by positron emission tomography. However, only 3
      had clearly abnormal caudate-thalamus activity ratios and 2 had clearly abnormal
      caudate-whole-slice ratios on single-photon emission computed tomography. These
      findings indicate that single-photon emission computed tomography imaging of
      caudate blood flow is a less sensitive indicator of caudate dysfunction in early
      HD than is positron emission tomography imaging of caudate glucose metabolism.

PMID- 7579752
TI  - Neoplastic meningitis with normal neurological findings. Magnetic resonance
      imaging results.
AB  - Neoplastic meningitis, an unusual complication of systemic cancer, is becoming
      more common as cancer patients live longer. Although leptomeningeal metastases
      from solid tumors are usually associated with multifocal neurological signs, the
      authors report on 4 patients who presented with normal findings on neurological
      examination. One man had severe headache and complex partial seizures. Magnetic
      resonance imaging (MRI) of the brain revealed gadolinium enhancement of multiple
      cranial nerves. Cerebrospinal fluid (CSF) cytology was positive for melanoma. One
      woman presented with severe migratory retroorbital headaches. MRIs of the brain
      with and without gadolinium appeared normal. CSF cytology was positive for
      pulmonary adenocarcinoma. One man presented with morning headache, and a woman
      presented with back pain. Both had CSF cytologies positive for lymphoma.
      Neoplastic meningitis can occur without abnormalities on neurological or MRI
      examinations. Lumbar punctures should be performed on cancer patients with
      severe, unusual, or prolonged headaches.

PMID- 7579754
TI  - Cranial arteriopathy in familial Vogt-Koyanagi-Harada syndrome.
AB  - A 59-year-old woman with Vogt-Koyanagi-Harada (VKH) syndrome presented with
      transient ischemic attacks. Magnetic resonance angiography showed multiple areas
      of stenosis affecting the intracranial portions of both internal carotid
      arteries. Conventional angiography confirmed these abnormalities and also
      demonstrated tapering stenosis of the extracranial segment of the left internal
      carotid artery. This patient and her similarly affected daughter represent the
      first reported association between cranial arteriopathy and intergenerational
      passage of VKH syndrome.

PMID- 7579753
TI  - Ultrasonography for diagnosis and management of carotid artery atherosclerosis. A
      position paper of the American Society of Neuroimaging.
AB  - The importance of identifying patients with carotid artery stenosis has attained
      greater significance in light of recent treatment trials of the efficacy of
      medical and surgical treatment of both symptomatic and asymptomatic carotid
      stenosis. Doppler and B-mode ultrasonography can accurately diagnose and quantify
      stenosis at the cervical carotid artery bifurcation. The development of duplex
      color-flow instruments has enhanced the sensitivity and specificity of this
      examination. Ultrasonography should be employed as an initial examination to
      identify patients with carotid artery stenosis and determine whether further
      evaluation or treatment is necessary.

PMID- 7579755
TI  - Traumatic abducens nerve paresis in a child.
AB  - Trauma is a frequent cause for abducens (sixth) nerve paresis in a child, usually
      attributed to injury along the nerve's course. An unusual focal lesion of the
      sixth nerve nucleus is described.

PMID- 7579756
TI  - Unusual lytic intraosseous meningioma.
AB  - Lytic intraosseous meningiomas are rare. This unusual case presented a diagnostic
      and treatment challenge.

PMID- 7579757
TI  - Rapid decompression of congenital hydrocephalus associated with parenchymal
      hemorrhage.
AB  - A newborn boy with congenital hydrocephalus was diagnosed with aqueductal
      stenosis using magnetic resonance imaging. Low-resistance ventriculoperitoneal
      shunt placement was followed by clinical deterioration. Repeat imaging studies
      revealed a collapsed cortical mantle with subdural hemorrhage. In addition to
      subdural blood, often associated with marked cerebral conformational changes,
      extensive intraparenchymal hemorrhage was seen. For extreme congenital
      hydrocephalus, ventriculoperitoneal shunts with greater resistance to flow than
      the currently used neonatal shunt devices may be indicated, to allow a more
      gradual ventricular decompression.

PMID- 7579758
TI  - Acute Wernicke's encephalopathy associated with hyperemesis gravidarum: magnetic
      resonance imaging findings.
AB  - A 25-year-old woman with hyperemesis gravidarum developed acute Wernicke's
      encephalopathy during prolonged intravenous fluid therapy without vitamin
      supplements. Delay in diagnosis led to a persistent severe neurological deficit,
      including coma. Gadolinium-diethylenetriaminepentaacetic acid-enhanced magnetic
      resonance imaging revealed symmetrical lesions around the aqueduct and fourth
      ventricle, which resolved after treatment with thiamine. She did not regain
      consciousness. This report demonstrates the diagnostic value of enhanced magnetic
      resonance imaging in acute Wernicke's encephalopathy.

PMID- 7579759
TI  - Transcranial Doppler detection of middle cerebral artery emboli before and after
      surgical closure of a patent foramen ovale.
AB  - This report describes the use of a combination of contrast transthoracic
      echocardiography and transcranial doppler to select emboli to the cerebral
      circulation in a patient with patent foramen ovale.

PMID- 7579760
TI  - Assessment of intracranial color-coded realtime sonography.

PMID- 7579761
TI  - Essentials of blood flow.
AB  - We have reviewed briefly some features of the mechanics of blood flow, focusing
      particularly on the arterial system. Among the topics we consider are: steady and
      nonsteady flow in straight rigid tubes; the curvature and branching of arteries,
      noting that it may commonly be nonplanar; and the effects of both planar and
      nonplanar curvature and branching on flow. Steady flow in planar bends and
      branches (and to a small extent in nonplanar bends and branches) has attracted
      study. However, there has been little study of nonsteady flow in either planar or
      nonplanar bends and branches.

PMID- 7579762
TI  - The assessment of pulsatile blood flow.

PMID- 7579763
TI  - Centrifugal blood pumps.

PMID- 7579764
TI  - Long-term blood pumping: an overview.

PMID- 7579765
TI  - Rotary blood pumps in circulatory assist.

PMID- 7579766
TI  - Pulse reverse osmosis: a new theory in the maintenance of fluid balance.

PMID- 7579767
TI  - Early experience with a true pulsatile pump for heart surgery.

PMID- 7579768
TI  - Low prime, heparin coated centrifugal pumps.

PMID- 7579769
TI  - Aortic cannula velocimetry.

PMID- 7579771
TI  - Chronic fatigue syndrome. 2: Treatment and future research.

PMID- 7579770
TI  - Psychomotor and mental development at four years of age: relation to psychosocial
      conditions and health. Results from a prospective longitudinal study.

PMID- 7579772
TI  - The relation of stress and depression to interdialytic weight gain in
      hemodialysis patients.
AB  - Nonadherence to fluid restrictions is a common problem with serious health
      consequences for patients with end-stage renal disease (ESRD). For the present
      study, the authors evaluated psychological variables of stress, as measured by
      major and minor life events, and depression. They sought to determine the role of
      these events in patients' failure to adhere to fluid restrictions as measured by
      increased interdialytic weight gain. Forty-two hemodialysis patients completed
      inventories assessing major life events, daily stressful events, and depression
      on three consecutive dialysis sessions. Fluid adherence was measured by
      interdialytic weight gain. A path analysis model found daily minor stress to have
      a direct effect on nonadherence, whereas there was a direct inverse effect of
      depression on nonadherence. Possible mechanisms and implications for future
      studies are discussed.

PMID- 7579774
TI  - Heart rate response to psychological stressors of individuals possessing resting
      bradycardia.
AB  - The authors examined the relation between trained and inherent bradycardia and
      heart rate (HR) and T-wave amplitude response to psychological stressors. They
      compared cardiac responses to two psychological stressors of 10 trained male
      runners (MVo2max = 75 mL/kg-1 min-1) possessing low resting heart rate (M = 58
      bpm), 10 untrained men (MVo2max = 58 mL/kg-1 min-1) with inherently low resting
      heart rate (M = 58 bpm), and 10 unconditioned men (MVo2max = 51 mL/kg-1 min-1)
      with normal resting heart rate (M = 69 bpm). All participants completed a maximal
      oxygen consumption treadmill test, an easy and a hard mental arithmetic task, and
      the Stroop Color and Word Test. Their analysis of the data revealed no
      significant differences in relative heart rate response or T-wave amplitude
      between groups during or after any stressor. In contrast, absolute heart rates
      during and after mental arithmetic and during the Stroop test were significantly
      lower for both the trained and inherently low groups compared with the control
      group. These findings suggest that the lower absolute HR response during and
      after stressors was influenced by both aerobic training and genetic inheritance.

PMID- 7579773
TI  - The role of exercise in weight loss.
AB  - Aerobic exercise has traditionally been viewed as a critical component of most
      weight-reduction programs. The resulting weight loss from the exercise alone,
      however, is often disappointing. Researchers too frequently fail to take into
      account the normal energy expenditure associated with living; the degree of
      obesity; the intensity and duration of the exercise itself; the activity during
      the recovery period; food intake before and after the exercise; and the age,
      gender, and training status of the individuals. Nor do they consider variations
      in baseline resting metabolic rates. In this article, the authors explore the
      effect of the intensity of aerobic exercise on weight loss, emphasizing the
      inability of many obese individuals to maintain an intensity level sufficient to
      produce significant weight loss. Aerobic exercise should be emphasized for its
      health benefits rather than as a short-term method of enhancing weight loss.

PMID- 7579775
TI  - Chronic fatigue syndrome. 1: Etiology and pathogenesis.
AB  - Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by
      debilitating fatigue and other somatic and neuropsychiatric symptoms. A range of
      heterogeneous clinical and laboratory findings have been reported in patients
      with CFS. Various theories have been proposed to explain the underlying
      pathophysiologic processes but none has been proved. Research findings of
      immunologic dysfunction and neuroendocrine changes suggest the possible
      dysregulation of interactions between the nervous system and the immune system.
      Without a clear understanding of its etiopathogenesis, CFS has no definitive
      treatment. Management approaches have been necessarily speculative, and they have
      evolved separately in a number of medical and nonmedical disciplines. The results
      of several controlled treatment studies have been inconclusive. An accurate case
      definition identifying homogeneous subtypes of CFS is needed. The integration of
      medical and psychologic treatment modalities and the use of both biologic and
      psychologic markers to evaluate treatment response will enhance future treatment
      strategies.

PMID- 7579776
TI  - Digoxin in the treatment of patients with chronic heart failure. Its place in
      therapy.

PMID- 7579777
TI  - Pharmacokinetic optimisation of drug therapy in elderly patients.
AB  - With increasing age, there are a number of physiological changes that affect the
      handling of drugs in the human body. Increases in body fat percentage as well as
      decreases in lean body mass, hepatic metabolism and renal elimination capacity
      are of particular clinical significance. It is important to take these changes
      into account when choosing drug therapy for older patients in order to minimise
      adverse effects and maximise potential benefits. This is particularly important
      when prescribing drugs with a narrow therapeutic index such as digoxin,
      theophylline, phenytoin, lidocaine (lignocaine) or warfarin. When available,
      monitoring of plasma concentrations can assist in the optimisation of drug
      dosage.

PMID- 7579778
TI  - P-glycoprotein expression and regulation. Age-related changes and potential
      effects on drug therapy.
AB  - P-Glycoprotein is a member of a superfamily of adenosine triphosphate-binding
      cassette transporter proteins and plays an important role in multidrug resistance
      in cancer cells. P-Glycoprotein is known to transport a wide variety of
      substances ranging from ions to peptides. P-Glycoprotein is expressed on a
      variety of normal cells, however its physiological function is unclear. The
      apical and polar distribution on secretory cells suggests a secretory role for P
      glycoprotein. More recently, cells of the immune system have been shown to
      express P-glycoprotein. There is evidence to suggest that P-glycoprotein may play
      a role in the secretion of certain cytokines (especially those lacking signal
      sequence) and cytotoxic molecules. In this article, the basic structure, gene
      regulation and expression of P-glycoprotein are reviewed. Furthermore, age
      related changes in the expression of P-glycoprotein and potential effects on drug
      therapy in the elderly are discussed.

PMID- 7579779
TI  - Rheumatoid arthritis in the elderly. Prevalence and optimal management.
AB  - Elderly-onset rheumatoid arthritis (EORA), defined as rheumatoid arthritis (RA)
      with onset at age 60 years or over, differs slightly from younger-onset RA by a
      more equal gender distribution, a higher frequency of acute systemic onset with
      involvement of the shoulder, a higher disease activity, and, in later stages,
      more radiographic damage and functional decline. Several subsets of EORA are
      recognised, such as rheumatoid factor-positive RA, polymyalgia rheumatica and
      'remitting seronegative symmetrical synovitis with pitting oedema'. These
      conditions can be difficult to distinguish from crystal-induced arthritis,
      osteoarthritis and paraneoplastic arthritis. The efficacy and tolerability of
      second-line drugs is similar in both age groups, but in the elderly caution is
      needed with the use of nonsteroidal anti-inflammatory drugs and prednisone.

PMID- 7579780
TI  - Drug-induced seizures in the elderly. Causative agents and optimal management.
AB  - We conducted a review of drugs that were most commonly associated with inducing
      seizures in the elderly population. The method for determining the risk of these
      agents includes evaluating the utilisation and the percentage of adverse events
      in previous studies and case reports. Classes of medications, such as anti
      psychotics and antidepressants, are extensively reviewed to provide the clinician
      with treatment options in high risk patients. The risk of seizures secondary to
      the withdrawal of alcohol (ethanol) and benzodiazepines, and methods employed to
      minimise the risk are discussed. In addition, the management of patients with
      drug-induced seizures is delineated. Drug-induced seizures are a potentially
      serious adverse effect. It is important that clinicians are aware of which
      classes of medications and individual medications are associated with reducing
      seizure threshold.

PMID- 7579782
TI  - Does the potential for development of streptokinase antibodies change the risk
      benefit ratio in older patients?
AB  - In patients with acute myocardial infarction (MI), quick initiation of
      thrombolytic therapy is the best strategy for improvement of survival and
      reduction of morbidity. Streptokinase, a purified product of haemolytic
      streptococci, is the most commonly administered agent. The compound anistreplase
      (a complex of streptokinase to plasminogen), is available but currently not often
      used. The non-antigenic competitor for these two compounds for the indication of
      MI is alteplase (recombinant tissue plasminogen activator, rt-PA). Due to former
      use of streptokinase or its derivative anistreplase, patients may develop
      specific antibodies to the foreign protein, whereas cross-reacting antibodies may
      be due to streptococcal infections. These antibodies may neutralise streptokinase
      or its derivative in case of (re)administration and may mediate adverse events,
      sometimes serious. Since advanced age by itself is certainly not a
      contraindication to thrombolytic therapy, and because reinfarction occurs
      frequently, the benefit-risk ratio of re-exposure to streptokinase or its
      derivative is decreased in the elderly who present with reinfarction. In the
      framework of tailored thrombolytic therapy, alteplase or urokinase appear to be
      the drugs of choice in these patients.

PMID- 7579781
TI  - Estramustine phosphate sodium. A review of its pharmacodynamic and
      pharmacokinetic properties, and therapeutic efficacy in prostate cancer.
AB  - Estramustine phosphate sodium (estramustine phosphate), a unique antitumour
      agent, is selectively taken up by prostate cells and exerts antineoplastic
      effects by interfering with microtubule of dynamics and by reducing plasma levels
      of testosterone. In noncomparative studies of estramustine phosphate in patients
      with hormone-refractory disease, objective response rates ranging from 19 to 69%
      have been reported. Preliminary clinical investigations indicate that combining
      estramustine phosphate with vinblastine, etoposide or paclitaxel improves
      objective response rates over single-agent treatment, although no survival
      benefit over single-agent treatment has been demonstrated to date. In comparative
      studies, estramustine phosphate produces similar objective response rates to
      conventional antineoplastic agents in patients with hormone-refractory prostate
      cancer. In previously untreated patients with advanced metastatic hormone
      responsive prostate cancer, objective responses are achieved in approximately 80%
      of patients. Estramustine phosphate appears to be at least as effective as
      estrogen or flutamide therapy in these patients. Nausea and vomiting are the most
      frequently observed adverse effects of treatment with estramustine phosphate.
      While these symptoms are usually mild to moderate in nature, they may
      occasionally be more troublesome to the patient and necessitate withdrawal of
      treatment. Cardiovascular complications are a more serious, though less
      frequently encountered, adverse effect of the drug. However, these complications
      may be avoided by careful patient selection and prophylactic treatment measures.
      Unlike some other antineoplastic agents, estramustine phosphate is rarely
      associated with myelosuppression. In addition to producing similar objective
      response rates to other established agents, estramustine phosphate improves the
      subjective status of many patients and has been shown to reduce the intensity of
      pain and improve the performance status of patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579785
TI  - Potential of melatonin replacement therapy in older patients with sleep
      disorders.

PMID- 7579783
TI  - Presymptomatic testing for genetic diseases of later life.
      Pharmacoepidemiological considerations.
AB  - As the Human Genome Project gathers speed, new disease genes are rapidly being
      found. Important as these discoveries are, they are only the beginning of the
      process of characterising, diagnosing and treating genetic diseases. We now have
      the potential to predict the onset of many disorders before the appearance of
      clinical symptoms, even though treatment is not always available. In this review
      we have used a number of examples to illustrate various aspects of the
      presymptomatic diagnosis of genetic disease and, where possible, late-onset
      disorders have been chosen as examples. When treatment is available, the
      diagnosis of a disease before appearance of symptoms can greatly improve the
      prognosis. When treatment is not available, reasons to undergo presymptomatic
      testing may not be so obvious. However, appropriate lifestyle changes or medical
      surveillance can sometimes delay onset or decrease severity of a disorder. Even
      if no treatment is available, genetic testing and counselling for the patient and
      family members can provide useful information for future planning.

PMID- 7579787
TI  - Optimising diuretic therapy in elderly patients with hypertension.
AB  - Hypertension is the most important risk factor for cardiovascular events in the
      elderly and it is present in more than 50% of acculturated populations over 60
      years of age. Morbidity trials have clearly demonstrated the benefits of treating
      hypertension in the elderly in all subgroups examined, including diabetics, those
      over 80 years of age, those with or without electrocardiographic abnormalities,
      and in both men and women. These reductions in strokes, coronary events, and
      other hypertensive complications have been seen primarily with diuretic-based
      regimens, with or without potassium-sparing therapy. However, in the 1990s
      physicians are initiating diuretics less often for older patients with
      hypertension in spite of this scientific evidence. Low doses of diuretics have
      been well tolerated, successful in recent morbidity trials, and avoid much of the
      concerns about theoretical toxicities from diuretics, although higher doses have
      also been shown to reduce cardiovascular events. Until calcium channel blockers,
      angiotensin converting enzyme inhibitors, alpha-blockers, or some other class of
      antihypertensive agent has been demonstrated to be at least as effective as
      diuretics in reducing cardiovascular events or mortality, diuretics should be the
      first drug class to consider for the treatment of hypertension in the elderly.

PMID- 7579786
TI  - Adjunctive therapy in patients with Alzheimer's disease. A practical approach.
AB  - Alzheimer's disease (AD) primarily results in memory impairment and cognitive
      deficits in areas such as language, visuospatial function, calculation, praxis
      and judgement. However, over 30% of patients with dementia develop a group of
      secondary behavioural disturbances, including depression, hallucinations and
      delusions, agitation, insomnia and wandering. Because these secondary symptoms
      impair patients' function, increase their need for supervision, and often
      influence the decision to institutionalise them, the control of these symptoms is
      a priority in managing AD. Psychotropic drugs, particularly antipsychotics
      (neuroleptics), have been a mainstay in treating many of these symptoms, but
      carry a high risk of adverse effects. Patients with AD may be particularly
      vulnerable to adverse effects of medications because of changes in
      pharmacokinetics and neurotransmitter systems, related to both AD and aging. At
      present, treating secondary symptoms of AD is more of an art than a science. For
      virtually every group of symptoms, older and newer classes of medications are
      available, with proven efficacy in patients without dementia and less clear
      results in AD patients. We review current treatment options and suggest
      preferences for each symptom complex, based on a trade-off between efficacy and
      adverse effects. New agents, such as selective serotonin reuptake inhibitors and
      atypical antipsychotics, may herald the arrival of symptom- (and receptor-)
      specific drugs with minimal adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579784
TI  - Epoetin alfa. A review of its clinical efficacy in the management of anaemia
      associated with renal failure and chronic disease and its use in surgical
      patients.
AB  - Epoetin alfa is a recombinant form of erythropoietin, a glycoprotein hormone
      which stimulates red blood cell production by stimulating the activity of
      erythroid progenitor cells. This review discusses the use of the drug in the
      management of anaemia in diseases often associated with advancing age [renal
      failure, cancer, rheumatoid arthritis (RA) and other chronic diseases, and the
      myelodysplastic syndromes (MDS)] and in surgical patients. Intravenous and
      subcutaneous therapy with epoetin alfa raises haematocrit and haemoglobin levels,
      and reduces transfusion requirements, in anaemic patients with end-stage renal
      failure undergoing haemodialysis or peritoneal dialysis. The drug is also
      effective in the correction of anaemia in patients with chronic renal failure not
      yet requiring dialysis and does not appear to affect renal haemodynamics
      adversely or to precipitate the onset of end-stage renal failure. Response rates
      of 32 to 82% with epoetin alfa therapy have been reported in patients with
      anaemia associated with cancer or cytotoxic chemotherapy. Limited data in
      patients with anaemia associated with RA show correction of anaemia after epoetin
      alfa treatment. Response rates to the drug of 0 to 56% have been noted in
      patients with MDS. Epoetin alfa also reduces anaemia, increases the capacity for
      autologous blood donation and reduces the need for allogeneic blood transfusion
      in patients scheduled to undergo surgery. Hypertension occurs in 30 to 35% of
      patients with end-stage renal failure who receive epoetin alfa, but this can be
      managed successfully with correction of fluid status and antihypertensive
      medication where necessary, and is minimised by avoiding rapid increases in
      haematocrit. Although vascular access thrombosis has not been conclusively linked
      to therapy with the drug, increased heparinisation may be required when it is
      administered to patients on haemodialysis. Epoetin alfa does not appear to exert
      any direct cerebrovascular adverse effects. Thus, epoetin alfa is a well
      established and effective therapy for the management of anaemia associated with
      renal failure. It also improves haematocrit and quality of life in patients with
      anaemia associated with cancer or chemotherapy. Epoetin alfa increases the
      capacity for blood donation and reduces the decrease in haematocrit seen in
      patients donating autologous blood prior to surgery. It also reduces, but may not
      eliminate, the need for allogeneic blood transfusion.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7579789
TI  - Separation of asparagine-linked oligosaccharides by high-pH anion-exchange
      chromatography with pulsed amperometric detection: empirical relationships
      between oligosaccharide structure and chromatographic retention.

PMID- 7579790
TI  - beta 1,4-Galactosyltransferase activity in B cells detected using a simple ELISA
      based assay.
AB  - Lymphocytic beta 1,4-galactosyltransferase (beta 1,4-GalTase, EC 2.4.1.38)
      activity was measured in B cells using a neoglyco-protein, N-acetylglucosamine
      phenylisothiocyanate-bovine serum albumin (GlcNAc-pITC-BSA), as an acceptor
      substrate in a novel enzyme-linked immunosorbent assay (ELISA)-based method. This
      assay proved to be much simpler to use than the lengthy and expensive
      radiochemical assays commonly used, and has the additional advantage that it
      specifically detects the enzyme mediating transfer via the Gal beta 1,4GlcNAc
      linkage. A F(ab')2 antibody against GalTase was able to specifically inhibit the
      reaction. Greater sensitivity for beta 1,4-GalTase activity was obtained using
      GlcNAc-pITC-BSA as an acceptor substrate rather than ovalbumin. Low levels of
      beta-galactosidase activity were detectable in lymphocyte cell lysates at acidic
      pH, although such activity was not detectable at the neutral pH used in the beta
      1,4-GalTase activity assay. Using this assay with the GlcNAc-pITC-BSA acceptor,
      similar beta 1,4-GalTase activities were observed in CD19+ B cells from patients
      with rheumatoid arthritis (RA) to those seen in normal control individuals.

PMID- 7579788
TI  - The role of beta-amyloid in the development of Alzheimer's disease.
AB  - Recent molecular biological, biochemical and immunohistochemical studies have
      revealed various novel facts about beta-amyloidosis including its role in the
      pathogenesis of Alzheimer's disease (AD). Such discoveries include the finding
      that beta/A4-amyloid protein (beta-AP) is the major component of the amyloid
      found in senile plaques (SPs) and amyloid angiopathy, the elucidation of the
      molecular structures of beta-AP and beta-amyloid protein precursor (APP), the
      finding that point mutations of APP are involved in some cases of familial AD
      (FAD), the location of genes for FAD, APP and Down's syndrome on chromosome 21,
      and of other genes relating to AD on chromosomes 19, 14 and 6, and the successful
      development of Alzheimer-type neuropathology in transgenic mice overexpressing
      V717F APP, a mutation of APP. Furthermore, the involvement of various proteases
      and their inhibitors in metabolism of beta-AP have been suggested by: the
      presence of Kunitz class serine protease and metalloprotease inhibitor domains on
      some APP, the presence of various proteases and inhibitors in SPs and
      neurofibrillary tangles (NFTs), the involvement of various proteases in the
      secretory and endosome/lysosome pathways of APP processing, mutation of the APP
      gene in hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D),
      mutation of the cysteine proteinase inhibitor cystatin C gene in HCHWA-I (Iceland
      type), and abnormal increases of some proteases or the inhibitors in dystrophic
      neurites of SP, amyloid of SP, and NFTs. Judging from these reports, dysfunction
      or deregulation of proteolytic systems may play an important role in beta-amyloid
      formation. Recent studies of beta-amyloid and various proteases and inhibitors in
      disorders associated with beta-amyloid formation are reviewed including our
      'overload hypothesis' as an underlying event in the dysfunction of proteolytic
      systems. This information should be helpful to identify targets in the
      development of drugs for the treatment of AD or other age-related disorders.

PMID- 7579792
TI  - Monoclonal antibody LU-BCRU-G7 against a breast tumour-associated glycoprotein
      recognizes the disaccharide Gal beta 1-3GlcNAc.
AB  - The monoclonal antibody LU-BCRU-G7, that was generated by in vitro immunization,
      shows clinical value as a prognostic marker in early stage breast carcinoma. It
      has now been characterized with regard to its binding epitope. Using a recently
      described method based on the construction of N-substituted polyacrylamide (PAA)
      derivatives of carbohydrates (pseudopolysaccharides), the structure of the
      epitope for the monoclonal antibody LU-BCRU-G7 has been determined. Competitive
      binding assays and inhibitory enzyme-linked immunosorbent assays (ELISAs) using
      these pseudopolysaccharides have shown the LU-BCRU-G7 epitope to be a
      disaccharide Gal beta 1-3GlcNAc (Lec; where Gal is D-galactose, Glc is D-glucose
      and GlcNAc is N-acetyl-D-glucosamine). Both galactose and N-acetyl glucosamine
      moieties are essential for binding. Substitution on C-2 or C-3 of the terminal
      galactose abolished binding, as did galactose-alpha terminated oligosaccharides.
      The galactose moiety alone, as expressed by the Gal beta-PAA conjugate, appeared
      to be a more important feature of the epitope than the GlcNAc-PAA conjugate,
      which failed to bind or inhibit the LU-BCRU-G7 antibody. In the N-acetyl
      glucosamine moiety, binding was decreased but not eliminated by fucose
      substitution, as in Lea, or change in configuration of C-4, as in Gal beta 1
      3GlcNAc. Omission of the NAc group resulted in complete loss of activity. The
      tetrasaccharide lacto-N-tetraose, although containing the terminal Lec
      disaccharide, does not react with the antibody, suggesting conformational
      interference of the binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579791
TI  - An endogenous lectin and its glycoprotein ligands are triggering basal and axon
      induced Schwann cell proliferation.
AB  - The proliferation of Schwann cells (the myelinating cells of the peripheral
      nervous system) is stimulated by the contact with axonal membranes. It is
      suggested that the endogenous carbohydrate-binding protein (lectin) cerebellar
      soluble lectin (CSL) bound to ligands at the surface of axonal preparations is
      mitogenic for Schwann cells. Both autocrine and axon-stimulated Schwann cell
      proliferations seem to be dependent on the presence of CSL and its ligands at the
      Schwann cell surface, as suggested by the effects of N-glycosylation inhibitors
      and anti-CSL Fab fragments. These data suggest that CSL regulates Schwann cell
      proliferation by clustering of a few glycoprotein ligands at the cell surface,
      consequently modulating phosphorylations.

PMID- 7579793
TI  - Separation of partially desialylated branched oligosaccharide isomers containing
      alpha (2-->3)- and alpha (2-->6)-linked Neu5Ac.
AB  - The following two tri-sialylated triantennary oligosaccharides, which differ only
      in the linkage of the Neu5Ac to the uppermost branch were, individually,
      partially desialylated to produce all possible di- and mono-sialylated isomers.
      [formula: see text] A tetra-sialylated triantennary isomer, which contained an
      alpha (2-->6)-linked Neu5Ac to the GlcNAc on branch III, was also converted to
      all possible trisialylated isomers by mild acid hydrolysis as previously
      described (Roher et al., Anal. Biochem., 212, 7-16, 1993). The resulting branch
      isomers were separated using high-pH anion-exchange chromatography (HPAEC).
      Structures were assigned to peak fractions on the basis of the previously
      described effect of alpha (2-->6)- and alpha (2-->3)-linked Neu5Ac on the elution
      order of branched lactosamine-type oligosaccharides (Townsend et al., Anal.
      Biochem., 182, 1-8, 1989). No differences in the acid lability of the Neu5Ac
      linkage to either Gal (alpha (2-->3) or alpha (2-->6)) or GlcNAc (alpha (2-->6))
      were observed. Our studies show that chemical desialylation and HPAEC is a useful
      approach to prepare and identify all possible sialylated branch isomers and
      should prove useful for defining the branch specificity of sialyltransferases and
      sialidases.

PMID- 7579794
TI  - The beta 1,4-galactosyltransferase gene is post-transcriptionally regulated
      during differentiation of mouse F9 teratocarcinoma cells.
AB  - Mouse F9 teratocarcinoma cells converted into primitive endoderm and parietal
      endoderm-like cells when treated with retinoic acid (RA) and RA plus dibutyryl
      cyclic AMP (dbtcAMP), respectively. The carbohydrate chains of glycoconjugates
      are known to undergo rapid changes during F9 cell differentiation. The mechanism
      of gene regulation of beta 1,4-galactosyltransferase (beta 1,4GalT), one of the
      glycosyltransferases involved in the synthesis of carbohydrate structures, was
      explored during the differentiation of F9 cells. Northern blot analysis revealed
      that the amount of beta 1,4GalT mRNA increased approximately 1.5- and 6.5-fold in
      response to treatment with RA alone and RA plus dbtcAMP (RA/dbtcAMP),
      respectively, for 8 days. beta 1,4GalT specific activity also gradually increased
      up to 21-fold in response to treatment with RA/dbtcAMP for 8 days. The reason for
      the different rates of increase in mRNA and enzyme activity remains to be
      determined. The transcriptional activity of the beta 1,4GalT gene was measured
      during the course of RA/dbtcAMP-induced F9 cell differentiation in transient
      transfection experiments using 5'-upstream region DNA (1.8 kb) of the mouse beta
      1,4GalT gene combined with luciferase cDNA. Although activity was slightly
      enhanced on the first day after induction, no significant rise in transcriptional
      activity was observed in the late stage of induction (3-6 days), when mRNA levels
      were greatly increased. This was further supported by the nuclear run-off assay
      which indicated that the rate of de novo synthesis of the beta 1,4GalT gene
      transcript in the RA/dbtcAMP-induced cells was almost the same as in
      undifferentiated F9 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579795
TI  - Recycling of a glycosylphosphatidylinositol-anchored heparan sulphate
      proteoglycan (glypican) in skin fibroblasts.
AB  - We have used suramin and brefeldin A to investigate the nature of a heparan
      sulphate proteoglycan that appears to recycle from the cell surface to
      intracellular compartments which synthesize new heparan sulphate chains. Suramin,
      which would block internalization and deglycanation of a putative recycling cell
      surface proteoglycan, markedly increases the yield of a membrane-bound
      proteoglycan with a core protein of 60-70 kDa and unusually long heparan sulphate
      side chains. When transport of newly made core proteins to their Golgi sites for
      glycosaminoglycan assembly is blocked, by using brefeldin A, [3H]glucosamine and
      [35S]sulphate incorporation into cell surface-bound heparan sulphate proteoglycan
      can still take place. After chemical biotinylation of cell surface proteins in
      brefeldin A-treated cells, followed by metabolic [35S]sulphation in the presence
      of the same drug, biotin-tagged [35S]proteoglycan can be demonstrated, indicating
      the presence of recycling proteoglycan species. By pre-labelling cells with
      [3H]leucine or [3H]inositol in the presence of suramin, followed by chase
      labelling with [35S]sulphate in the presence of brefeldin A, a 3H- and 35S
      labelled, hydrophobic heparan sulphate proteoglycan with a core protein of 60-65
      kDa is obtained. The proteoglycan loses its hydrophobicity when glucosamine
      inositol bonds are cleaved, indicating that it is membrane bound via a
      glycosylphosphatidylinositol anchor. However, treatment with phosphatidylinositol
      specific phospholipase C has no effect, suggesting that the inositol moiety may
      be acylated. We propose that a portion of the lipid-anchored proteoglycan
      glypican is internalized, recycled via the Golgi, where heparan sulphate chains
      are added, and finally re-deposited at the cell surface.

PMID- 7579796
TI  - Genomic organization of core 2 and I branching beta-1,6-N
      acetylglucosaminyltransferases. Implication for evolution of the beta-1,6-N
      acetylglucosaminyltransferase gene family.
AB  - Two human beta-1,6-N-acetylglucosaminyltransferases forming the core 2 O-glycan
      branch, C2GnT and the I antigen, IGnT, are homologous to each other in three
      regions of the catalytic domain (A, B, C) and their genes reside at the same
      locus, chromosome 9, band q21 (Bierhuizen,M.F.A., Mattei, M.-G. and Fukuda,M.,
      Genes Dev., 7, 468-478, 1993). In order to investigate how these two enzymes are
      related at the genomic level, and how this gene family evolved, we have
      elucidated their genomic structures. It was found that C2GnT is coded by two
      exons, of which the second exon encodes the whole translation product. In
      contrast, the complete coding sequence for IGnT is divided over three exons.
      Importantly, the highly homologous region B is encoded entirely by exon 2 in the
      C2GnT gene, while the same region is split between exons 1 and 2 in the IGnT
      gene. The other highly homologous regions, A and C, are also encoded by exon 2 in
      the C2GnT gene, while they are encoded by exon 1 and exon 3, respectively, in the
      IGnT gene. These results strongly suggest that the common ancestral gene was
      first duplicated and then each duplicated gene evolved into the C2GnT or IGnT
      gene by intron insertion and divergence following the duplication. The sequences
      upstream from the transcription initiation sites of the C2GnT and IGnT genes have
      promoter activity and contain TATA-like sequences.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579797
TI  - Utilization of sialic acid-binding synthetic peptide sequences derived from
      pertussis toxin as novel anti-inflammatory agents.
AB  - Pertussis toxin, a virulence factor produced by the organism Bordetella
      pertussis, has been shown to have functional similarities with selectins and to
      bind to similar sialic acid-containing oligosaccharides structures. Previously,
      we demonstrated that the amino-terminal region of the S2 subunit of pertussis
      toxin contained a short six amino acid sequence (SPYGRC) which displayed
      reasonable homology to a sequence that constitutes a portion of the sialic acid
      binding site in wheat germ agglutinin. Synthetic peptides containing this
      hexapeptide motif had the ability to bind to sialic acid-containing
      glycoconjugates including the putative oligosaccharide receptors (sialyl Lewis X
      and sialyl Lewis A) for selectins. Control peptides containing randomized
      sequences were inactive at inhibiting binding, indicating that the hexapeptide
      motif is important for interacting with sialic acid. Since pertussis toxin
      derived peptides demonstrated the ability to interact with selectin receptors, we
      speculated that they should antagonize selectin-mediated inflammatory activity.
      To test this hypothesis, we evaluated the peptides for the ability to reduce
      neutrophil binding to activated endothelial cells as well as the anti
      inflammatory activity in the mouse footpad swelling assay. Both S2 peptides were
      active at reducing neutrophil binding and footpad swelling, while the randomized
      control peptides were inactive.

PMID- 7579798
TI  - Characterization of a 21 amino acid peptide sequence of the laminin G2 domain
      that is involved in HNK-1 carbohydrate binding and cell adhesion.
AB  - The N-linked HNK-1 carbohydrate expressed by several recognition molecules
      mediates the adhesion of early post-natal cerebellar neurons to the G2 domain of
      the terminal globular domain of the laminin alpha 1 chain (H. Hall et al.,
      submitted). To define this binding site more precisely, G2-derived synthetic
      peptides were used for binding and competition studies. Peptide 5-G2, comprising
      the amino acid residues 3431-3451 of G2, inhibited the interaction between the
      HNK-1-carrying glycolipid and laminin in a concentration-dependent and saturable
      manner. Peptides which overlap only partially with this sequence interfered less.
      Peptides comprising other amino acid sequences from G2, and peptides derived from
      G1 and G3 or a scrambled version of peptide 5-G2, did not show significant
      effects. Direct binding of peptide 5-G2 to the HNK-1 glycolipid was also
      demonstrated. Furthermore, peptide 5-G2 interfered in a concentration-dependent
      and saturable manner with the adhesion of early postnatal cerebellar neurons to
      laminin. These observations indicate that amino acid residues 3431-3451 of the
      laminin G2 domain are involved in HNK-1 carbohydrate-mediated cell adhesion.

PMID- 7579799
TI  - CD23 molecule acts as a galactose-binding lectin in the cell aggregation of EBV
      transformed human B-cell lines.
AB  - Epstein-Barr virus (EBV)-transformed human B-cell lines, L-KT9 and DH3 cells
      express CD23 antigen, and grow in a mixture of single and aggregated cells. The
      CD23 molecule has high amino acid sequence homology with C-type lectin and
      recently we have shown that the solubilized CD23 molecule can really interact
      with galactose residues on glycoproteins. In this study, therefore, we tested
      whether CD23 antigen on the cell surface really acts as a galactose-binding
      lectin in the aggregation of these cells. The EBV-transformed cells (L-KT9) were
      separated into an aggregated-cell-rich fraction and a single-cell-rich fraction.
      Aggregated cells disaggregated after removal of galactose by beta-galactosidase
      treatment, whereas single cells made large aggregation on sialidase treatment,
      and this aggregation was inhibited in the presence of asialo-fetuin. On the other
      hand, naturally aggregated cells become single cells with anti-CD23 monoclonal
      antibody (mAB) as well as the soluble form of CD23, but not with anti-CD21 mAB.
      In addition, L-KT9 and DH3 cells bound to asialo-fetuin-coupled Sepharose (ASF
      Sepharose) and this binding was significantly inhibited by pre-treatment of cells
      with anti-CD23, but not with anti-CD21 or other anti-adhesion molecules. From
      these results, we conclude that the naturally aggregated state of EBV-transformed
      cells occurs mainly through the interaction of CD23 as a lectin molecule and
      galactose residues as its ligand.

PMID- 7579800
TI  - Acetylcholinesterase-positive afferent axons in mucosa of urinary bladder of
      adult cats: retrograde tracing and degeneration studies.
AB  - Acetylcholinesterase (AchE)-positive afferent axons in the mucosa of the cat
      urinary bladder were examined in the present experiments. Small-sized dorsal root
      ganglion cells containing AchE enzyme activity were labelled by injection of
      retrograde tracer (wheat germ agglutinin conjugated to enzymatically inactive
      horseradish peroxidase gold complex) into the bladder mucosa of adult cats.
      Results show that 48.9% (90/184) of the labelled ganglion cells possessed AchE
      enzyme activity. Following unilateral dorsal root ganglionectomy (L2-5, S1-3), a
      total of 6619 unmyelinated axon terminals were examined in the bladder mucosa,
      including 691 degenerating axon terminals. Percentages (8.;6-16.1%) of
      degenerating axon terminals in the ganglionectomized animals (1, 2, 3, 10 and 21
      days post-operated) were significantly higher than those of controls (3.1%) and
      the 60-day post-operated animals (3.2%). Approximately one-half (47.9%) of the
      degenerating axon terminals observed in the 1-21 day post-operated animals were
      AchE-positive. Further examination also disclosed that the population of the
      intact (not affected by ganglionectomy) AchE-positive axon terminals at 60 days
      (59.3%) was significantly greater than that of controls (45.6%). The AchE
      positive terminals containing few synaptic vesicles were significantly increased
      in number in the 60 day post-operated cats. In conclusion the present study
      demonstrates that one half of afferent axons in the mucosa were AchE-positive.
      The increase in AchE-positive afferent axon terminals containing few synaptic
      vesicles may be derived from contralateral dorsal root ganglia resulting from
      sprouting following dorsal root ganglionectomy.

PMID- 7579801
TI  - p53 in breast cancer. Its relation to histological grade, lymph-node status,
      hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2.
      Immunohistochemical study of 153 cases.
AB  - The mutation of the p53 gene is a common phenomenon in numerous human tumors,
      leading to the accumulation of nonfunctioning p53 protein in the cell nucleus,
      which can be detected by immunohistochemistry. In breast cancer, it has been
      suggested that the overexpression of p53 protein in the nucleus is an indicator
      of poor prognosis, which must be borne in mind in selecting coadjuvant treatment
      for each patient. This study is an immunohistochemical analysis of p53 expression
      in 153 cases of mammary carcinoma, correlating it with histological grade,
      axillary node status, hormone receptors, cell-proliferation fraction and
      expression of the c-erbB-2 oncoprotein. Of all the breast-cancer tissue analyzed,
      43.79% was positive for p53. The overexpression of this protein bears a direct
      statistically significant relationship to histological grade, cell-proliferation
      fraction and c-erbB-2, and an inverse relationship to estrogen and progesterone
      receptors. No statistically significant relationship was found with axillary node
      status. The expression of p53 in poorly differentiated tumors-commonly receptor
      negative and with a high proliferation fraction-may indicate greater tumor
      aggressiveness and a high risk of relapse.

PMID- 7579802
TI  - Nuclear vlimata and aneuploidy in embryonic cells is caused by meiosis. Behaviour
      and properties of meiotic cells.
AB  - This study demonstrates that human embryonic cells divide by meiosis. The use of
      trophoblastic tissue cells (early embryo) and amniotic cells (late embryo)
      exhibited the following characteristic events of meiosis: nuclear (NVs) and
      nucleolar (NuVs) vlimata formation; NV invasion in host cells; extrusion of
      chromosomes; nuclear fusion; metaphase fusion; hybrid cell formation; nuclear,
      nucleolar and cytoplasmic bridges, chromosomal transfer, variable-sized nuclei;
      nuclear fragmentation; condensed meiotic chromosomes; "O" chromosome; and
      aneuploidy. Two types of nuclear bridges (NBs) were identified and defined as
      communicative tubules through which chromosomal transfer among cells is achieved.
      The wall of NBs is an extension of the nuclear membrane and the lumen contained
      chromosomal fusion substance (CFS). Embryonic cells formed glycosaminoglycan-sacs
      (GSG-sacs) and rivulets, forming a cytoplasmic communicative system. The
      extracellular matrix (ECM), GSG-sacs and CFS were composed of glycosaminoglycan
      bound protease. The protease which immuno-crossreacted with the a1-chymotrypsin
      antiserum was the meiotic calcium-activated activated neutral proteinase (CANP).
      Cytogenetic analysis of early embryonic cells showed higher ratio of
      aneuploidy:diploidy than late embryonic cells. The results are discussed in terms
      of differentiation-mitosis and undifferentiation-meiosis. These observations lead
      to an embryonic cell life cycle identical to that of malignant cells as follows:
      [formula: see text].

PMID- 7579803
TI  - Assessment of cyclosporine A-induced ultrastructural changes in vascular wall
      using an experimental arterial autograft model.
AB  - The objective of this ultrastructural study was to assess the effects of
      cyclosporine A (CsA) in an experimental model of arterial autograft. Fifty female
      Sprague-Dawley rats weighing 250-300 g were employed. Using a microsurgical
      technique, an arterial autograft measuring approximately 5 mm in length was
      placed in the right common iliac artery. Two groups were established: group I
      (control), consisting of 25 animals subjected only to arterial autograft; and
      group II (pre- and postoperative CsA), also consisting of 25 animals which
      received a daily subcutaneous dose of 5 mg/kg CsA (Sandimmun, Sandoz) on the four
      days preceding the surgery and thereafter, until sacrifice. The animals were
      sacrificed on postoperative day 7, 14, 21, 30 and 50. The specimens (autografts)
      obtained were studied under transmission and scanning electron microscopes. In
      the control group, the process of endothelialization of the graft was completed
      by day 14. In the CsA-treated group, restoration of the endothelium took 50 days.
      The development of intimal hyperplasia was delayed in the treated group. There
      were no morphological changes in its structure when compared to the control
      group. The tunica media had thinned in the treated grafts, with loss of smooth
      muscle cells, fragmentation and lysis of the elastic lamina, presence of lipid
      filled macrophages, and muscle cells with cytoplasmic lipid vacuoles. In our
      opinion, these results suggest that the action of CsA mainly targets on the
      endothelium and smooth muscle cells, exerting a toxic effect in an in vivo
      arterial graft model.

PMID- 7579804
TI  - Modifications in the distribution of met-enkephalin in the limbic system of the
      cat brain after electroacupuncture. An immunocytochemical study.
AB  - The distribution of met-enkephalin in the limbic system of the cat brain and its
      modification after low frequency electroacupuncture (EA) stimulation have been
      studied experimentally using the indirect immunocytochemistry technique. A marked
      increase of post-stimulation met-enkephalin immunoreactivity was observed in the
      tractus habenulo-penduncularis, tractus mamilo-thalamicus, and medial forebrain
      bundle, and a decrease at the level of the nucleus interpeduncularis, medialis
      dorsalis, stria terminals, septalis lateralis, septalis medialis, accumbens
      septi, supraopticus, and amygdaloideus centralis. The experimental results link
      the changes in immunoreactivity (and therefore the structures in which they take
      place) with the action of low frequency EA, and permit the conclusion that the
      met-enkephalinergic portion of the limbic system studied is directly related
      morpho-functionally with analgesia and the anatomic pathways of pain.

PMID- 7579805
TI  - The role of proteoglycans in maintaining collagen fibril morphology.
AB  - The aortic wall contains various heterogenous proteoglycan populations which
      interact in different ways with other components of extracellular matrix.
      Proteoglycans (PGs) are known to provide structural support to the vessel wall as
      well as to influence specific physiological functions of the tissues. The aim of
      the present study was to investigate the effects of Chondroitinase AC (Chase),
      Streptococcal Hyaluronidase (Hyase) and Heparanase on human aortic wall collagen
      which had been treated previously with 4M GuHCl, in order to verify the effects
      of selective glycanolytic treatment on type I collagen fibril ultrastructure.
      Following 4M GuHCl treatment, collagen fibrils are seen to have a clearly visible
      period. Subsequent to GuHCl and Streptococcal Hyase treatment all collagen
      fibrils appear to be completely swollen in thin aperiodic filaments; the typical
      64 nm collagen period is completely undetectable. After GuHCl and Chase treatment
      a small number of collagen fibrils are seen to be swollen in thin fibrils which
      are mainly localized at some distance from elastic fibres. Following GuHCl and
      Heparanase/Heparitinase III treatment a considerable number of collagen fibrils
      appear to be swollen in thin fibrils; the majority of which are situated in the
      vicinity of elastic fibrils. The swelling of collagen fibrils underlines the
      fundamental role of proteoglycans in maintaining collagen fibril integrity and
      periodicity. It is as yet impossible to precisely map interactions between these
      proteoglycans and collagen fibres. The role of Hyaluronic acid requires further
      investigation, although the nature of this interaction is undoubtedly a matter of
      considerable interest.

PMID- 7579806
TI  - Blood vessel morphometry in human colorectal lesions.
AB  - Neovascularisation in tumours of different cell origins has been well documented
      qualitatively. In this report, we have assessed vascular architecture in
      different pathological lesions of the colorectum by quantifying blood vessel
      parameters in order to detect subtle morphological changes using objective
      methods. Colorectal tissue samples were obtained from resected large bowels
      containing malignant tumours. Biopsies were taken from defined sites in the
      resected specimen and were classified as normal (N), potentially premalignant
      mucosa (PPM), adenomatous polyp (P) and adenocarcinoma (ADCA). All tissues were
      fixed in modified Karnovsky's fixative for 4 hrs and postfixed in 1% OsO4 for 1
      hr. Samples were processed for EM under standardized procedures and embedded in
      Epon. 0.5 microns semithin sections from five patients per group were stained
      with toluidine blue. A multistage systematic sampling procedure was adopted. The
      inner outlines of all blood vessels in the lamina propria (LP) were digitised
      using a Zeiss VIDAS Image Analyzer at a final magnification of x1,050. The area
      of the reference (LP) was also measured. No attempt was made to distinguish
      between the different types of vessel. The morphometric blood vessels parameters
      quantified were volume density (Vv), numerical density (NA), length density (LV)
      and mean transverse sectional area (A). Statistically significant differences in
      Vv and A were detected between all groups except between N and PPM and between P
      and ADCA. No significant differences in NA and LV were present in any group
      comparisons. The mean values of all parameters were the highest in ADCA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579807
TI  - Jacalin, another marker for histiocytes in paraffin-embedded tissues.
AB  - Jacalin is a lectin which reacts with D-galactose. We have tested jacalin on 75
      samples of different formalin- and alcohol-fixed tissues. A consistent
      cytoplasmic stain of the histiocytes was observed in paraffin-embedded tissues in
      all cases studied of reactive sinus histiocytosis, macrophages in clear centres
      of follicular hyperplasia, in tuberculosis granulomas and in osteoclast-like
      giant cells in a breast carcinoma. We failed to find any clear binding of jacalin
      to the cells of eosinophilic granulomas, giant cell tumors of tendon sheath,
      pleomorphic malignant fibrous histiocytomas, Hodgkin's disease, melanomas, nevi
      or signet ring cell carcinomas of the breast and stomach. It seems that jacalin
      is a good marker for free histiocytes/macrophages, not for fixed histiocytes and
      tumors related to them. This lectin might play a role in differential diagnosis
      with histiocyte mimicking processes.

PMID- 7579809
TI  - Immunohistochemical study of p53 expression in cancer tissues from patients
      undergoing radiation therapy.
AB  - Immunostaining using p53 monoclonal antibodies (p53(Ab-3) recognizes mutant type
      and p53(Ab-6) the wild type of p53 protein) was performed on frozen sections of
      biopsy specimens obtained before and during preoperative radiotherapy from 23
      patients with head and neck squamous cell carcinoma. The positive staining rates
      of p53(Ab-3) before radiotherapy and at radiation doses of 4Gy, 10Gy and 20Gy
      were 30.0%, 38.9%, 25.0% and 6.25%, and those of p53(Ab-6) 10.5%, 11.8%, 5.0% and
      0% respectively. The relationship between the immunohistochemical findings and
      antitumor effect at radiation dose of 20Gy was examined on the correspondent
      haematoxylin-eosin sections. In patients whose p53(Ab-3) stainings were positive
      at any doses of radiotherapy, the antitumor effect at the cumulative dose of 20Gy
      waas either remarkable or effective. Moreover, the frequency of the expression of
      mutant type p53 protein tended to increase in rather radiosensitive tumors. As
      for wild type p53 protein, there was no remarkable relationship between the
      staining of p53(Ab-6) and the antitumor effect.

PMID- 7579808
TI  - Immunohistochemical analysis of adrenal proliferation and corticosterone
      expression in experimental adrenal regeneration.
AB  - The proliferative activity, the organization and the corticosterone expression of
      adrenocortical cells in an experimental adrenal regeneration process after the
      transplantation of neonatal adrenal glands to adult hosts was investigated. Three
      days after transplantation, the medullar and the innermost adrenocortical cells
      of the neonatal adrenal glands showed degenerative and necrotic changes due to
      the lack of vascular supply. The remaining outermost adrenocortical cells did not
      display any PCNA immunoreaction. The first PCNA expression, pointing out the
      beginning of the proliferative cycle, was observed in a 45.4% of the
      adrenocortical cells, one week after transplantation. After three weeks, several
      regenerated adrenocortical nodules with a bigger size than the one observed in
      the previous periods were seen. In these nodules, while the outermost
      adrenocortical cells were disposed in parallel to the capsule or in rounded
      groups, the bulk of the regenerated mass width was composed of cells forming
      longitudinal cords. PCNA immunoreaction was almost exclusively restricted to
      subcapsular cells (62.5%) and to cells of the outermost portion of the cords
      (32.5%), the global percentage of PCNA immunopositive cells being 18.4%. Twelve
      weeks after transplantation, regenerated adrenocortical cells were arranged in
      three layers: glomerulosa, fasciculata and reticularis. Only 1.85% of the
      adrenocortical cells were PCNA immunopositive. Although in the early stages of
      the regeneration process, all the adrenocortical cells, both proliferating and
      non proliferating cells expressed corticosterone, a restriction of this
      immunoreactivity to the zonae fasciculata and reticularis was observed when cell
      zonation was apparent.

PMID- 7579810
TI  - Effects of sex steroids on the Syrian hamster liver.
AB  - The primary objective of this research project was to study the role of sex
      steroids in the pathogenesis of cholelithiasis using the Syrian hamster as a
      model. In addition to the morphological examination of the gallbladder
      epithelium, we thought it imperative to observe the changes induced in the
      biliary tract in response to the sex steroid treatment. This report focuses on
      the morphological changes induced in the liver. The hamsters were randomly
      divided into 4 groups, control (C), estrogen-treated (E), estrogen and
      medroxyprogesterone-treated (E+MP), and medroxyprogesterone-treated (MP) groups.
      The E group hepatocytes demonstrated proliferation of the smooth endoplasmic
      reticulum, lipofuscin-like granules, aggregates of glycogen rosettes, and dense
      bodies. Lipid droplets in the hepatocyte cytoplasm as well as the nuclei were
      detected in this group. E+MP combined treatment induced an exacerbation of all
      the changes observed in the E group, furthermore, there appeared to be a
      disruption of the hepatic parenchymal architecture. The MP-treated group also
      exhibited the architectural changes observed in the E+MP group, but also showed
      sinusoidal dilation. In response to MP alone, the fatty changes in the liver
      appeared to be accentuated. A striking feature induced in response to MP
      treatment, was a focal area suggestive of adenomatous changes.

PMID- 7579811
TI  - Effect of chronic alcoholism on neuronal nuclear size and neuronal population in
      the mammillary body and the anterior thalamic complex of man.
AB  - The effect of chronic alcoholism on neuronal nuclear size and neuronal population
      of two memory-related diencephalic centres, the mammillary body and the anterior
      thalamic complex, has been examined in 24 chronic male alcoholics and 22 age
      matched male controls. Cases were subdivided into three age groups (30-44 years,
      45-59 years and 60-75 years). The results showed a significant reduction in both
      neuronal numbers and nuclear size in alcoholics compared to controls. Differences
      were especially high in the youngest alcoholics. The intensity of liver damage
      (steatosis vs. cirrhosis) did not have any significant effect. Moreover, an age
      related decrease of neuronal number and karyometry was seen in controls but not
      in alcoholics. Our results suggest that chronic alcoholism accelerates the rate
      of neuronal loss in the mammillary body and anterior thalamic complex to a degree
      equivalent to aging. Likewise, chronic alcoholism impairs the compensatory
      increase in neuronal nuclei area seen in normal aging in these same structures.
      Our findings show that medial diencephalic memory centres are damaged in chronic
      alcoholism, which may contribute to the clinical symptomatology of these persons.

PMID- 7579812
TI  - Immunoreactivity for c-fos and c-myc protein with the monoclonal antibodies 14E10
      and 6E10 in malignant mesothelioma and non-neoplastic mesothelium of the pleura.
AB  - We studied immunoreactivity for c-fos protein and c-myc protein in malignant
      mesothelioma (36 cases) and non-neoplastic pleural mesothelium (45 cases) using
      the murine monoclonal antibodies 14E10 and 6E10. All malignant mesotheliomas and
      cases with non-neoplastic mesothelium exhibited not only nuclear but also
      cytoplasmic immunoreactivity for c-fos and c-myc protein in the majority of
      mesothelial cells. There was no statistically significant difference between the
      various mesothelioma subtypes or between neoplastic and non-neoplastic
      mesothelium for c-fos protein immunoreactivity (p > 0.05). There was
      statistically significant difference between neoplastic and non-neoplastic
      mesothelium for c-myc protein immunoreactivity (p < 0.01). We conclude that
      immunoreactivity for c-fos and c-myc protein is present in both non-neoplastic
      and neoplastic mesothelium, but that a higher proportion of neoplastic
      mesothelial cells are immunoreactive for c-myc protein when compared with non
      neoplastic mesothelium.

PMID- 7579813
TI  - Immunohistochemical demonstration of secretory IgA in human urothelium.
AB  - The mucosal surface of the human urothelium represents a very large exposure area
      to exogenous agents, including potentially harmful microorganisms. Male human
      urothelium was treated for the immunohistochemical demonstration of secretory IgA
      (sIgA) in order to verify its own possible antimicrobial properties. An intense
      immunoreactivity for sIgA was observed in the apical cells of the urethral and
      vesical epithelia. The ureteric epithelium, at the luminal surface, showed
      discontinuous areas of less dense or completely absent reaction product. A less
      intense immunoreactivity was observed in the pelvic apical epithelial cells. The
      results suggest that sIgA play a prominent role in the local defence mechanisms
      of the lower urinary tract against ascending infections, whereas in the upper
      urinary tract the immuno-specific local defences seem reduced.

PMID- 7579815
TI  - Prognostic significance of p53 and c-erbB-2 immunohistochemical evaluation in
      colorectal adenocarcinoma.
AB  - Mutant p53 tumour suppressor gene and c-erbB-2 proto-oncogene are involved in
      human carcinogenesis, and their protein product detection in human malignancies
      might influence the evolution of many neoplasms. Our aim was to estimate their
      association with histopathological and clinical parameters of prognostic value in
      colorectal cancer. An immunohistochemical assay was undertaken in formalin-fixed
      sections from tissue specimens of 60 colorectal carcinomas. Nuclear p53
      expression was detected in 46.6%, while membranic c-erbB-2 positivity was noticed
      in 35% of the examined cases. P53 positivity rate significantly correlated with
      poor differentiation (p < 0.001), high mitotic activity (p < 0.0001), tumour
      stage (p < 0.001) and 5-year overall survival period (p < 0.01). C-erbB-2
      positivity incidence significantly correlated with advanced Dukes' stage (p <
      0.001) and high mitotic activity (p < 0.05). Significant association between p53
      and c-erbB-2 immunostaining was observed (p < 0.05) and p53/c-erbB-2 co
      expression was related to poor differentiation (p < 0.001), high mitotic activity
      (p < 0.001), advanced Dukes' stage (p < 0.001), tumour aneuploidy (p < 0.05) and
      worse overall survival (p < 0.05). P53 and c-erbB-2 immunohistochemical detection
      in combination with known prognostic indicators may be a useful future tool in
      determining colorectal cancer prognosis and subsequently in deciding on optimal
      postoperative treatments.

PMID- 7579814
TI  - Immunomorphological characteristics of renal cell carcinoma.
AB  - Immunomorphological characteristics of 27 renal cell carcinoma (RCC): 18 clear
      cell, 6 granular (chromophilic), 2 chromophobe, 1 spindle cell (sarcomatoid) as
      well as of 1 oncocytoma, were analyzed. The investigation was performed on
      cryostat sections by immunoperoxidase technique applying a panel of monoclonal
      antibodies which defined: proximal (TNE3, TN5, 5D9) and distal (TN8, TN9, 7C2)
      tubular antigens; intercellular adhesion molecule 1 (ICAM1); HLA class II (-DQ, 
      DR and -DP) antigens, intermediary filaments (cytokeratin and vimentin); and
      antigens on tumour infiltrating mononuclear leucocytes (TT1, TT2 and LeuM3 for
      CD4, CD8 and CD14 antigens, respectively). All RCC with exception of chromophobe
      co-expressed cytokeratin and vimentin. In addition, they were usually positive
      for all proximal and two distal tubular markers (TN8, TN9) indicating primitive
      cells which could differentiate into the epithelium of both parts of tubule
      system as the most probable originators of in RCC. Almost all RCC but the
      chromophobe aberrantly expressed HLA class II antigens which great variability
      from case to case. The presence of HLA-DR antigens was more intensive and
      widespread than of HLA-DQ and -DP antigens. Expression of ICAM1 mostly correlated
      with presence of HLA class II antigens, particularly with -DR on tumour cells of
      RCC. HLA-DR antigen expression was always more prominent than mononuclear cell
      infiltrate (among which macrophages prevailed over T cells) which could suggest
      that increased histocompatibility antigen expression precedes mononuclear cell
      influx. In contrast to all other RCC, chromophobe tumours had quite distinct
      features revealing the most intense reaction with 7C2 (MAb that produced the
      weakest reaction with other tumour types), absence of vimentin and very weak
      reaction with antibodies for HLA class II Ag and ICAM1.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579816
TI  - Hyperplastic innervation of vasoactive intestinal peptide in human gallbladder
      with cholelithiasis.
AB  - The vasoactive intestinal peptide (VIP) immunoreactive nerve fibres in the
      gallbladder from 14 human patients with cholelithiasis was examined by
      immunohistochemical method. In the chronic cholecystitis, hyperplastic VIP
      immunoreactive nerves were observed around the hypertrophied muscle bundles,
      Rokitansky Aschoff Sinus and in the mucosal layer. However, in the acute
      cholecystitis and gangrenous cholecystitis, reduction or disappearance of VIP
      nerve fibres was observed. These reductions or disappearances of VIP
      immunoreactive nerves may secondly result from severe tissue damage. These
      results suggest that hyperplastic VIP nerves cause gallbladder relaxation, stasis
      and mucosal fluid unbalance, which may closely correlate to gallstone formation.

PMID- 7579817
TI  - Scanning electron and light microscopic observations on the healing process after
      sintered bone implantation in rats.
AB  - The healing process after implantation of sintered bone in the rat parietal bone
      was compared with that of synthetic hydroxyapatite using both scanning electron
      and light microscopy. The results showed that the differences between the
      sintered natural bone and the synthetic hydroxyapatite implantations were in the
      states of bone union and the bioresorbability of the implanted materials, even
      though both materials consist of the same hydroxyapatite. In the sintered bone
      implantation, the newly formed bone invaded into the material at 1 to 2 weeks
      after implantation. The sintered bone surface on the dura mater side was
      completely covered by the new bone at 5 weeks. It is noteworthy that bone
      resorbing areas characterized by Howship's lacunae were observed on the sintered
      bone surface at 2 weeks and the material was replaced by new bone. Light
      microscopy, which revealed the invasion and the development of the new bone into
      the sintered bone, supported the scanning electron microscopic observations. In
      the synthetic hydroxyapatite, the new bone adhered closely to the material just
      like the sintered bone implantation. The new bone did not invade into the
      synthetic hydroxyapatite. There was no evidence of the resorption of the
      hydroxyapatite. This shows that the natural and the biological structures of the
      sintered bone offer an advantageous environment to fluid circulation and ingrowth
      after implantation.

PMID- 7579819
TI  - Distribution of immunoreactive transforming growth factor-alpha in non-neoplastic
      human salivary glands.
AB  - The distribution of immunoreactive transforming growth factor-alpha (TGF-alpha)
      was studied in non-neoplastic human major and minor salivary glands using an
      immunoperoxidase assay in conjunction with an antiserum to human TGF-alpha. The
      ductal cell components of all major and minor salivary glands were found to
      contain significant amounts of TGF-alpha immunoreactivity. In contrast, acinar
      and myoepithelial cells consistently lacked immune reaction product in both types
      of glands. Occasionally, an asynchronous pattern of TGF-alpha ductal cell
      immunoreactivity was observed in specific ducts within a section. Also,
      intraductal secretions, when present, were found to contain TGF-alpha
      immunoreactive material. Ductal cells and connective tissue from salivary glands
      samples showing significant lymphocytic infiltration and loss of acinar cells
      exhibited higher levels of TGF-alpha immunoreactivity than normal salivary gland
      samples. These observations demonstrate, for the first time, the presence of TGF
      alpha immunoreactivity in specific structural components of non-neoplastic human
      major and minor salivary glands. It will be important in future studies to
      determine whether alterations in TGF-alpha expression are detectable in diverse
      types of salivary gland tumors.

PMID- 7579818
TI  - Ultracytochemical study of trimetaphosphatase activity during acrosomal formation
      in the mouse testis.
AB  - The localization of Trimetaphosphatase (TMPase) activity during the acrosomal
      formation in the mouse testis was enzyme cytochemically investigated by the
      cerium-salt method. In addition to the lysosomes of the Sertoli cells and the
      spermatogenic cells in the seminiferous tubules, positive TMPase activity was
      detected in the Golgi complex and in the acrosomal vesicles of the spermatids, as
      well as in the acrosomes of both spermatids and spermatozoa. In the Golgi complex
      of the spermatids, TMPase activity was observed in the first one or two lamellae
      of the trans-face and in the small vesicles in the vicinity of the Golgi complex.
      TMPase positive reaction was also detected in the acrosomes of the spermatozoa in
      the lumina of both the seminiferous tubules and the epididymal duct. The
      localization of this enzyme activity was compared with that of acid phosphatase
      (ACPase), as detected by the cerium-based method, using beta-glycerophosphate as
      substrate: ACPase activity was completely absent from the Golgi complex, small
      vesicles, acrosomal vesicle and acrosome throughout the entire process of
      acrosomal formation. TMPase is thought to become one of the acrosomal components,
      and may be involved in the acrosomal reaction during fertilization.

PMID- 7579820
TI  - Analysis of cell proliferation kinetics during the secondary palate development
      in quail.
AB  - A study was undertaken to analyze the spatio-temporal pattern of mesenchymal cell
      proliferation in the developing palate of quail. Quail embryos were grown in
      shell-less culture. The developing palates were labelled with 3H-thymidine
      between culture days 2-6 (which corresponded in vivo incubation days 5-9), and
      processed for light microscopic autoradiography. Percent labelled mesenchymal
      cells were determined. The data showed that, as in mammals, a high rate of random
      cell proliferation in mesenchyme was a major component of early palate
      development in quail. As the palate morphogenesis advanced, the rate of cell
      proliferation declined. Segmental analysis, however, indicated that, in contrast
      to mammals, the mesenchymal cell proliferation rates continually changed in
      various regions of quail palate during morphogenesis. It was suggested that the
      spatio-temporal changes in the distribution of dividing cells may reflect
      differences in the timings of cell cycles between various segments, thus
      resulting in a heterogeneous population of cells in the developing palate of
      quail. Further, the differences in the segmental pattern of cell proliferation
      between birds and mammals may form the basis for differences in the morphogenesis
      of their palates.

PMID- 7579821
TI  - Age-related changes of aorta in Syrian hamsters of APA strain.
AB  - Age related changes in thoracic aorta (TA) and abdominal aorta (AA) of male APA
      hamsters from 3 to 12 months of age were examined morphometrically and
      ultrastructurally. The nuclear density of smooth muscle cells (SMCs) was larger
      in AA than in TA, and it decreased with advancing age. In contrast, the collagen
      fibre density was larger in TA than in AA, and it increased correlatively with
      aging, especially in TA. Electron microscopic examinations revealed that
      subendothelial cystic spaces and aggregations of fragments of elastic and
      collagen fibres were found at 3 months of age and progressed with advancing age
      in TA, while they were not evident in AA even at 12 months of age. Irregularity
      of medial SMC contours and an amount of SMC-associated collagen fibres were more
      prominent in TA than in AA throughout the experimental period. Degenerative
      changes of endothelial cells and medial SMCs progressed with aging in both TA and
      AA, and degenerated SMCs were characterized by aggregations of swollen
      mitochondria.

PMID- 7579822
TI  - Peripheral nerve injury and regeneration.
AB  - The process of nerve regeneration has been studied extensively by traditional
      morphological methods, but it is only recently that has been possible to identify
      more precisely the contribution of different nerve subpopulations. By studying
      different models of nerve repair and regeneration, it is becoming apparent that
      other tissue components are contributing to the overall process. When muscle
      grafting is carried out to repair an injured nerve, the regenerating axons are
      migrating in parallel with Schwann cells to bridge the nerve gap. The presence of
      Schwann cells is essential for a successful nerve regeneration, most probably
      because their production of different neuronal trophic factors. This pattern is
      also repeated when fibronectin mats are used for nerve repair, indicating the
      possibility to use this new synthetic matrix for clinical application. If the
      target organ is analysed after nerve repair, the recovery of all nerve components
      is evident. However, the process occurs at different times in separate skin
      compartments, and the regeneration of the autonomic innervation appears to be
      preceded by that of the sensory nerves. When looking at cutaneous nerve
      regeneration following different type of injury, a common pattern of events
      becomes apparent. In skin flaps, nerve regeneration begins from the skin
      surrounding the wound edge, or from the pedicle, and sensory nerves are the first
      to penetrate into the flap. Angiogenesis precedes reinnervation of the flap, and
      initially regenerating fibres appear to be associated with newly formed blood
      vessels. This pattern is evident also in full-thickness wounds and in suction
      blisters, where only the more superficial cutaneous layer is disrupted.
      Furthermore, the presence of keratinocytes appears to exert a directional
      influence on both regenerating blood vessels and nerves, which follow the
      regenerating keratinocytes when reepidermalisation is taking place. These results
      would indicate that there is a close relationship between nerve fibres and blood
      vessels during regeneration, with a substantial contribution to the process from
      other tissue components and soluble factors from the surrounding environment.

PMID- 7579823
TI  - Macrophages in the external muscle layers of mammalian intestines.
AB  - The literature on macrophages in the muscularis externa of mouse, rat, guinea
      pig, cat, dog and human gut is reviewed. In smaller mammals macrophages are
      regularly situated in two locations: in the serosa and at the level of Auerbach's
      plexus between the longitudinal and circular muscle layers. In addition a few
      solitary cells are present at the level of the deep muscular plexus. At the level
      of Auerbach's plexus the macrophages occur as a constant and regularly
      distributed cell population with intimate associations between macrophages and
      interstitial cells of Cajal. Morphologically they differ from most resident
      macrophages in being irregular in shape with 4-6 primary cytoplasmic processes,
      which branch and give a stellate appearance. They have been demonstrated with
      endocytotic markers (trypan red, FITC-dextran, cholera toxin),
      immunocytochemically with macrophage antibodies (F4/80, M1/70) and antibodies
      against MHC class-II antigen, GABA and cGMP. In muscularis externa of the human
      gut a regularly distributed cell population of macrophages is not obvious.
      However, a phenotypically distinct subgroup is identified by light microscopy
      with the pan macrophage antibodies (EBM11, C3b1 and partly by p150.95), and shows
      MHC class-II antigen. By electron microscopy muscularis externa macrophages, in
      all species investigated, appear to be endocytically downregulated, and since
      they are lysozyme, prostaglandine H synthase (both constitutive and activated)
      and acid phosphatase negative, they appear to be inactivated cells. Both origin
      and function of these cells are unknown. They may be immuno-competent,
      participate in a neuroimmune axis, tissue growth and modulation or other
      regulations of specific cell functions.

PMID- 7579824
TI  - Classification of salivary gland tumours--a brief histopathological review.
AB  - Tumours of the salivary glands display a wide variety of histological
      appearances, and vary in behaviour from totally benign to high grade and usually
      fatal malignancies. Over the past 40 years several classification schemes have
      been proposed, of which the most comprehensive and accurate are those of the
      Armed Forces Institute of Pathology (AFIP) and the World Health Organization
      (WHO) which were both revised in 1991. They are readily applicable by practising
      surgical pathologists, and encompass most of the range of tumours likely to be
      encountered. If I have a slight preference, it is for the WHO classification
      which is more concise. This paper briefly discusses each tumour, and highlights
      the changes from previous classifications, including the proper recognition of
      several newly described tumours which are distinct clinico-pathological entities.
      Neither of the new schemes solves every problem, and brief attention is drawn to
      defects. These are minor, and do not significantly detract from the advantages of
      both new classifications, which represent a major advance in our ability to
      understand these often perplexing tumours.

PMID- 7579825
TI  - Genetic markers and animal models of neurocristopathy.
AB  - Neurocristopathy is the disorder in which the series of cell and tissue derived
      from the neural crest are affected. A variety of neural crest tumors, and
      systemic neurocristopathies such as neurofibromatosis type 1 (NF1) and type 2
      (NF2), multiple endocrine neoplasia type 2 (MEN2) and dysplastic nevus syndrome
      are included in this category. Genetic abnormalities of specific proto-oncogenes
      and tumor suppressor genes have been discovered in the neurocristopathies. The
      NF1 gene has GTP-ase activating protein activity, regulates ras pathway and acts
      as a potential tumor suppressor. The NF2 gene, which is also considered as a
      tumor suppressor of Schwann cell and meningocyte, has a unique character that it
      is a linker between adhesion molecule and cytoskeletal protein. Ret proto
      oncogene has been proven to be the responsible gene not only of MEN2A but also of
      MEN2B, familial medullary carcinoma and Hirschsprung disease. Recent progress of
      positional cloning technique further revealed that p16 gene which is an inhibitor
      of cycline-dependent kinase is the gene for some of familial malignant
      melanoma/dysplastic nervus syndrome and sporadic melanoma. ENU-induced rodent
      model for human Schwann cell tumor and fish model for malignant melanoma have
      provided useful insights to molecular mechanisms of neural crest tumors.
      Moreover, introduction of transgenic and gene targeted mouse models for
      neurocristopathies has made great progress in understanding of the genetic
      functions in tumoriginesis.

PMID- 7579826
TI  - The relevance of cell microenvironments for the appearance of lympho-haemopoietic
      tissues in primitive vertebrates.
AB  - In higher vertebrates, mainly in mammals, a role for the non-lymphoid components
      of lymphoid organs in governing the maturation and functioning of immune system
      has been largely demonstrated. In contrast, such a role in the evolution of the
      vertebrate immune system has only been evidenced indirectly. In the present
      review we summarize histophysiological results which emphasize the relevance of
      lympho-haemopoietic stromal elements in the emergence and evolution of vertebrate
      lymphoid organs. The most primitive vertebrates, the Agnatha, have no true
      lymphoid organs and, accordingly, their immune responses seem more related to the
      non-anticipatory defence mechanisms of invertebrates than to the immune responses
      of vertebrates. So, the appearance and evolution of vertebrate lymphoid organs
      seems closely related with the emergence of immune capacities. Thymus, spleen and
      gut-associated lymphoid organs appear early in phylogeny whereas lymph nodes and
      bone marrow are late phylogenetical adquisitions. However, bone marrowless
      vertebrates contain numerous organs (i.e., gonads, kidney, brain, etc...), the
      cell microenvironments of which support lympho-haemopoiesis mimicking the
      condition of higher vertebrate bone marrow. On the other hand, the lack of
      germinal centres, another feature of the lymphoid organs of ectothermic
      vertebrates which impedes the selection of B cells raised after somatic
      hypermutation, presumably reflects the absence of some of the elements necessary
      for this organization.

PMID- 7579827
TI  - Frontiers in Perioperative Myocardial Management. Proceedings of a workshop.
      Montreal, Canada, October 27-30, 1994.

PMID- 7579828
TI  - Cardiovascular morbidity and CABG surgery--a perspective: epidemiology, costs,
      and potential therapeutic solutions.
AB  - Although substantial advances have been made in the management of cardiovascular
      disease, it remains the leading cause of death on the United States and many
      other countries, due to the impact of aging and other changes in patient
      demographics. Since cardiovascular complications are usually associated with
      stress, it is not surprising that perioperative complications (cardiac death,
      myocardial infarction, heart failure) occur in at least 10% of patients
      undergoing coronary artery bypass graft surgery, with such complications
      consuming an additional $2 billion annually in health care resources. In
      addition, the limitations of the newly mandated cost-saving methods have and will
      continue to have an impact upon the delivery of health care to cardiovascular
      patients. However, research and clinical studies in this area hold the promise of
      appropriate and cost-effective therapeutic approaches.

PMID- 7579829
TI  - Clinical aspects of preconditioning and implications for the cardiac surgeon.
AB  - Ischemic preconditioning is one of the most powerful means to reduce myocardial
      ischemic cell death in the experimental laboratory. Data are now emerging
      suggesting that ischemic preconditioning also can occur in the human heart.
      Studies performed on human myocardial biopsies, angioplasty studies, clinical
      studies assessing acute tolerance to angina, and some studies evaluating the
      effect of angina prior to myocardial infarction, lend support to the concept that
      the human heart can be preconditioned. The ultimate objective is to develop
      preconditioning-mimetic agents that can be administered prophylactically prior to
      the time of cardiopulmonary bypass surgery or administered to hearts that have
      been harvested for transplant in order to better preserve the ischemically
      jeopardized myocyte.

PMID- 7579830
TI  - Biological perspective on "myocardial preconditioning".
AB  - There has been an upsurge of research on myocardial preconditioning because of
      its potential clinical application in areas such as cardiology, cardiac surgery,
      and transplantation. From a broad biological standpoint, a conceptual framework
      may help in both promoting understanding and suggesting future research paths.
      The living organism's tendency toward developing evolutionarily advantageous
      strategies has led to a fight or flight response, for which the authors consider
      preconditioning a component. Added to preconditioning, the production of stress
      proteins and altered myocardial states (especially that of "hibernating
      myocardium") can be seen as a series of biological strategies developed and
      maintained during evolution. An increased understanding of the mechanisms
      involved in the body's self-defense strategies should lead to better approaches,
      those in which we can help the cells, including those comprising the myocardium,
      to preserve themselves.

PMID- 7579831
TI  - Myocardial preconditioning: a model or a phenomenon?
AB  - A brief ischemic episode (ischemic preconditioning) limits myocardial necrosis
      produced by a prolonged period of coronary artery occlusion and reperfusion. In
      absence of infarction, lack of cumulative ATP depletion, and ventricular
      arrhythmias and dysfunction "stunning" in models of intermittent ischemia and
      reperfusion also could be a component of an adaptive response to brief ischemia
      (preconditioning). Nonischemic stimuli also precondition the myocardium against
      ventricular arrhythmias and infarction by activating endogenous mechanism(s) of
      protection similar to that induced by ischemic preconditioning. Preservation of
      myocardial ATP, abolishing purine release, attenuation of free radical
      production, activation of adenosine receptors and KATP channels, and induction of
      heat shock proteins are common responses to ischemic and nonischemic stimuli of
      preconditioning. Although a significant reduction in myocardial infarction is
      critical to myocardial salvage and patient survival, it is equally important to
      have a functioning heart that can sustain systemic pressure without inotropic
      support or assist devices. It is scientifically challenging and clinically
      important to elucidate the mechanisms of myocardial preconditioning. However, it
      is necessary to expand the definition of myocardial preconditioning to include
      nonischemic stimuli of preconditioning and other important monitors of myocardial
      protection such as ventricular function and electrophysiological stability in
      addition to that of infarction.

PMID- 7579832
TI  - Low-dose i.v. acetylcholine acts as a "preconditioning-mimetic" in the canine
      model.
AB  - Brief episodes of ischemia paradoxically protect or "precondition" the heart and
      reduce infarct size caused by a subsequent, more sustained, coronary artery
      occlusion, perhaps by stimulation of adenosine receptors coupled to muscarinic
      receptors via the inhibitory G protein. However, brief ischemia is not a
      desirable form of therapy. Using the anesthetized canine model, we therefore
      sought to determine if small intravenous (i.v.) doses of the muscarinic agonist
      acetylcholine would provide a therapeutically feasible means to mimic
      preconditioning. Four groups of dogs underwent a 40-minute intervention period,
      followed by 1 hour of coronary occlusion and 5 hours of reperfusion: 8 received
      two i.v. doses of acetylcholine (0.01 mg each) at 40 minutes and 5 minutes before
      the sustained occlusion; 8 received equipotent doses of nitroglycerin (0.05 mg; a
      vasodilator that does not act via the M2 muscarinic receptor); 7 received
      conventional ischemic preconditioning (four 5-minute episodes of coronary
      occlusion, each interrupted by 5 minutes of reperfusion); and 8 controls received
      no intervention. Coronary blood flow and hemodynamic parameters were monitored
      throughout the protocol, regional myocardial blood flow was measured during the
      sustained occlusion by injection of radiolabeled microspheres, and infarct size
      was assessed by tetrazolium staining. All four groups were equally ischemic
      during coronary occlusion. However, infarct size was reduced significantly in
      both the preconditioned and acetylcholine-treated dogs when compared with
      controls (6% +/- 2% [p < 0.01 vs controls], 10% +/- 2% [p < 0.05 vs controls],
      and 19% +/- 3% of the myocardium at risk).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579833
TI  - Acute regional myocardial ischemia and recovery after cardiopulmonary bypass:
      effects of intensity of antecedent ischemia.
AB  - Aortic cross-clamping with inadequate myocardial preservation has been shown to
      cause postoperative decreases in myocardial performance following coronary artery
      bypass graft surgery. We have demonstrated a mild decrement in myocardial beta
      receptor function associated with cold cardioplegia in a normal animal model; in
      normal human hearts, however, response to beta-adrenergic inotropic stimulation
      was diminished significantly. Beta-receptor dysfunction also is associated with
      chronic myocardial ischemia that is associated with severe ischemic heart
      disease. Although the change in beta-receptor function with acute regional
      myocardial ischemia associated with severe ischemic heart disease is not
      understood fully, we found that the intensity of regional ischemia significantly
      affects functional recovery after cardiopulmonary bypass (CPB). Myocardial
      stunning does not appear to be significant in this dysfunction; however,
      alterations in beta-receptor density and function may play a critical role in
      post-CPB ventricular function.

PMID- 7579834
TI  - Myocardial self-preservation: absence of heat shock factor activation and heat
      shock proteins 70 mRNA accumulation in the human heart during cardiac surgery.
AB  - Following myocardial ischemia, heat shock proteins (HSPs) have been found to be
      associated with a reduction in infarct size and enhanced postischemic functional
      recovery. Stress-induced regulation of the HSPs is mediated by the activation and
      binding of the heat shock transcription factor (HSF) to a specific DNA sequence
      located in front of all HSP genes, known as the heat shock element (HSE). To
      determine whether HSPs were induced in the human heart following the ischemic
      stress experienced during cardiac surgery, biopsies were performed of the right
      atrium at three sequential times: prior to establishing cardiopulmonary bypass;
      immediately after aortic declamping; and following termination of bypass. These
      samples from the atria of patients undergoing coronary bypass surgery were
      assessed for HSF activation using mobility shift gels, and analyzed for HSP 72
      mRNA by Northern blot. Although a high level of the HSP 72 protein was noted at
      all intervals, no HSF activation was detected, nor was an accumulation of HSP 72
      mRNA observed at any time during surgery. These data suggest that HSPs are not
      induced during cardiac surgery and that the high "constitutive" level of the HSP
      72 protein detected in these hearts may not be secondary to an HSF-HSE
      interaction, but rather, the result of other transcription factors acting at
      alternative regions of the HSP 70 promoter.

PMID- 7579835
TI  - Anti-CD18 attenuates deleterious effects of cardiopulmonary bypass and
      hypothermic circulatory arrest in piglets.
AB  - Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest induce leukocyte
      and platelet activation and cytokine production as part of the inflammatory
      response to bypass. These events are thought to be responsible for producing at
      least some of the morbidity of bypass. We studied the effects of a monoclonal
      antibody to a specific leukocyte adhesion integrin, CD18, on the deleterious
      effects of CPB and circulatory arrest in piglets using techniques from infant
      heart surgery. Seventeen immature piglets were subjected to CPB, cooling, 1 hour
      of circulatory arrest at 15 degrees C, and subsequent reperfusion and rewarming.
      Nine piglets received anti-CD18 monoclonal antibody (group MAb), and eight
      randomly selected control piglets received none (group C). Monoclonal antibody to
      leukocyte integrin CD18 significantly decreased deleterious effects of CPB and
      hypothermic circulatory arrest in our immature animal model. This study suggests
      that antiadhesion therapy that alters fundamental leukocyte/endothelial
      interactions during open heart surgery may be protective against some deleterious
      effects of bypass and circulatory arrest in infants.

PMID- 7579836
TI  - Cytokine induction during cardiac surgery: analysis of TNF-alpha expression pre-
      and postcardiopulmonary bypass.
AB  - Cytokines are soluble mediators that possess both intra- and intercellular
      signaling properties. Their function has been investigated most thoroughly in the
      context of immune reactions. Cytokines, however, form an important component of
      the inflammatory response to trauma and are found in elevated concentrations
      following cardiopulmonary bypass (CPB). We were, therefore, interested in
      studying mRNA expression for the cytokine tumor necrosis factor alpha (TNF-alpha)
      in patients undergoing cardiac surgery. White cells isolated from the circulation
      of seven patients before and after CPB were assayed for the expression of mRNA
      with TNF-alpha specific primers using the polymerase chain reaction. Message for
      TNF-alpha was found in all patients, with the highest values demonstrated in
      patients whose CPB times exceeded 1 1/2 hours. Enhanced message expression was
      seen as early as 1 hour after the start of CPB. Genes responsible for cytokine
      (TNF-alpha) expression and production are activated during cardiac surgery.

PMID- 7579838
TI  - Hypothermia reversibly inhibits endothelial cell expression of E-selectin and
      tissue factor.
AB  - Hypothermia frequently accompanies cardiopulmonary bypass (CPB) and myocardial
      protection strategies during cardiac surgery. With CPB, the blood/artificial
      surface interface activates components of the humoral and cellular inflammatory
      cascades and may contribute to postoperative end organ dysfunction including the
      heart or multiple other organ systems. The endothelial cell (EC) monolayer
      normally mediates components of solute transport, vasomotor function,
      coagulation, cell differentiation/growth, and immune/inflammatory processes. E
      selectin is a vascular adhesion molecule that mediates neutrophil adherence and
      that is inducible in ECs by inflammatory mediators such as cytokines. Tissue
      factor (TF) is similarly an inducible procoagulant factor in ECs that contributes
      to thrombosis. The induction, transcription, and expression of both molecules
      were studied in cultured human umbilical vein cells at normothermic (37 degrees),
      hypothermic (25 degrees), and rewarmed (37 degrees) conditions after stimulation
      with the cytokines tumor necrosis factor alpha and interleukin-1. Hypothermia
      reversibly inhibits the transcription and expression but not the induction of
      both E-selectin and TF.

PMID- 7579837
TI  - Augmentation of microvascular nitric oxide improves myocardial performance
      following global ischemia.
AB  - Hearts exposed to global myocardial ischemia associated with cardiac surgery
      often suffer postischemic endothelial and contractile dysfunction related to
      antecedent regional or global ischemia. Our studies tested the hypothesis that
      supplementing blood cardioplegia and reperfusion with the nitric oxide (NO)
      precursor L-arginine or the NO donor SPM-5185 would preserve endothelial
      function, reduce infarct size, and reverse postcardioplegia regional contractile
      dysfunction or global dysfunction. In the first study involving 23 anesthetized
      dogs undergoing regional ischemia, supplementation of blood cardioplegia with L
      arginine: (1) reduced infarct size; (2) improved postischemic regional segmental
      work and diastolic stiffness; (3) attenuated neutrophil accumulation in the area
      at risk; and (4) improved postischemic depressed coronary artery endothelial
      function. The NO synthase inhibitor N-nitro-L-arginine (L-NA) reversed these
      protective effects. In another experiment involving 18 anesthetized dogs
      undergoing normothermic global ischemia, hearts treated with blood cardioplegia
      supplemented with the NO donor SPM-5185 demonstrated better postischemic coronary
      artery endothelial function, lowered myeloperoxidase activity in the ischemic
      reperfused myocardium, and significantly improved global ventricular function in
      the group receiving high-dose SPM-5185. We conclude that the inclusion of L
      arginine or high-dose NO donor SPM-5185 in blood cardioplegia improves
      postischemic ventricular performance and endothelial function in ischemically
      injured hearts, possibly by inhibition of neutrophil-mediated damage via the L
      arginine-NO pathway.

PMID- 7579839
TI  - Endothelial function following ischemia.
AB  - The consequences of ischemia and reperfusion on endothelial dependent and
      independent coronary flow patterns following a variety of ischemic insults in
      isolated perfused rabbit hearts were studied. A blood perfused ex vivo model was
      developed that provided reliable and stable systolic performance comparable to
      crystalloid perfused hearts, but with a four to sevenfold decrease in resting
      coronary flow and a three to six fold increase in coronary flow reserve compared
      to Krebs' perfusion. Following incremental graded 37 degrees C ischemia of 10 to
      45 minutes, blood perfused hearts had compromised systolic performance, but
      unaffected response to exogenous endothelial dependent and independent agonists
      whereas in crystalloid perfused hearts, the response to these same agonists was
      blunted prior to noting a decrement in systolic function. Further studies
      assessed the consequences of 30 and 45 minutes of ischemia on the regulatory role
      of basal nitric oxide released by the coronary endothelium. In both blood and
      crystalloid perfused hearts, basal nitric oxide secretion had a significant and
      persistent regulatory role on coronary vascular tonus over a tenfold range of
      coronary flow despite ischemic injury that severely depressed systolic
      performance. Finally, hearts were preserved in University of Wisconsin (UW) or
      St. Thomas' (ST) solutions for 4 hours at 4 degrees C. With crystalloid
      perfusion, ST results in impaired postischemic response to both endothelial
      dependent and independent agonists. After UW preservation and with all blood
      perfused hearts, postischemic flow patterns were unchanged. Using physiological
      blood perfusion protocols, the endothelium and arterial smooth muscle were found
      more resistant to ischemia-reperfusion injury than the myocyte.

PMID- 7579841
TI  - The electrophysiology of ischemia and cardioplegia: implications for myocardial
      protection.
AB  - The primary goal of modern cardioplegia is to protect the heart during the
      periods of cardiac arrest and global ischemia that are required to perform
      cardiac surgery. In order to achieve this, cardioplegic solutions must be able to
      arrest rapidly the electrical activity of the heart. An understanding of the
      electrophysiology of cardioplegia is critical to an adequate understanding of its
      basic mechanisms of action. This article reviews recent advances in our
      understanding of the electrophysiological changes seen during ischemia and
      cardioplegia. Although 10 years ago, depolarization and repolarization were
      attributed to changes in membrane resistance, advances in molecular biology have
      elucidated that the mechanism of the action potential is governed by ionic
      transport across hydrophobic lipid membranes through carefully regulated pores
      formed by members of an extended family of ion channel proteins. There also have
      been great strides in our understanding of the heart's electrophysiological
      response to ischemia. One of the most dramatic responses to ischemia is a
      profound shortening of the cardiac action potential, which has been shown to be
      cardioprotective by limiting calcium influx into the cell. ATP-sensitive
      potassium channels have been confirmed to play a critical role in the action
      potential shortening seen during ischemia. Drugs that open these channels have
      been shown to limit infarct size, attenuate myocardial stunning, and ameliorate
      reperfusion injury. Recent work has demonstrated that these drugs may be
      effective cardioplegic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579840
TI  - The role of ATP sensitive potassium channels in myocardial protection.
AB  - Several factors have pointed to a potential link between ATP sensitive potassium
      channel activation in ventricular myocytes and the phenomenon of myocardial
      preconditioning. Preconditioning can be blocked by adenosine antagonists, and is
      mimicked by adenosine A1-receptor agonists. A portion of the physiological action
      of adenosine is, however attributable to adenosine actions on KATP channels. The
      adenosine A1 receptor is reported to be linked to the KATP channel in rat
      ventricular myocytes by a G-protein mechanism. This article will review the
      current status of work regarding the role of KATP channels in myocardial
      preconditioning and will highlight recent work addressing the role of anesthetic
      effects in these studies. Recent reports and work from our laboratory reveal that
      several commonly used anesthetic drugs either have direct effects on KATP
      channels (barbiturates) or have prominent physiological effects that are
      modulated in large part by KATP channels (volatile anesthetics halothane and
      isoflurane).

PMID- 7579842
TI  - Effects of edema on systolic and diastolic function in vivo.
AB  - Recent advances in the study of myocardial edema are reviewed. A rat model,
      developed for the study of diastolic properties, is differentiated from larger
      mammals by less myocardial water content in the control state, by less
      cardioplegia-induced edema, and by more rapid evolution of ischemic contracture.
      The model has proven useful in defining the time course of recovery from
      iatrogenic edema, which requires less than 15 minutes, and in defining the time
      course and determinants of changes in compliance during transplant rejection. In
      pigs, a new experimental model allows study of left ventricular (LV) mass
      variation and changes in systolic and diastolic properties during resolution of
      iatrogenic edema. Initial studies indicate that iatrogenic edema and related
      increases in LV stiffness resolve in less than 45 minutes in pigs, in the absence
      of substantial ischemic injury. No significant changes in systolic performance
      were demonstrable statistically, but contractility was depressed immediately
      after reperfusion, requiring inotropic and mechanical circulatory support. In
      patients, measured changes in intraoperative LV mass are small and require
      correction for effects of changes in LV volume to define significance.

PMID- 7579843
TI  - Linearity, load dependence, hysteresis, and clinical associations of systolic and
      diastolic indices of left ventricular function in man. Multicenter Study of
      Perioperative Ischemia (McSPI) Research Group.
AB  - Measures of left ventricular (LV) contractility must be linear, load-independent,
      free of hysteresis, and sensitive to changes in inotropic state. These properties
      of measures of LV contractility have been assessed previously in animals, but
      never in man. Using a micromanometer and volume conductance catheter technology,
      we measured LV pressure and volume in 67 patients scheduled for CABG surgery.
      Measurements of the maximum rate of change of pressure relative to time versus
      end-diastolic volume (dP/dtMax-EDV), preload recruitable stroke work (PLRSW) and
      the end-systolic pressure-volume relationship (ESPVR), and measurements of the
      maximum negative rate of change of pressure relative to time versus end-diastolic
      volume (-dP/dtMax-EDV) and the end-diastolic pressure-volume relationship (EDPVR)
      were obtained in 62 patients. Comparisons of these measures of contractility
      during preload reduction and augmentation were performed in 48 patients using
      paired and unpaired student's t-tests. Index linearity was determined using
      linear regression analysis. Neither the slope nor the intercept of any of the
      three measures of contractility changed significantly with loading conditions.
      Heart rate demonstrated no physiologically significant baroreceptor-mediated
      changes during the perturbations. Comparing measures of LV function--ejection
      fraction (EF%), LV end-diastolic pressure (LVEDP), dP/dtMax-EDV, PLRSW, ESPVR, 
      dP/dtMax-EDV, and end-diastolic pressure-volume relationship (EDPVR)--in patients
      with a preoperative medical history of congestive heart failure (CHF), myocardial
      infarction (MI), and hypertension (HTN) demonstrated lower EF percent (62.4 +/-
      16.7 vs 42.8 +/- 5.0 [p < 0.0002]) and lower ESPVR (2.27 +/- 1.98 vs 1.30 +/-
      0.83 [p < 0.03]) in patients with a history of CHF.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7579844
TI  - Risk factors for stroke following coronary bypass surgery.
AB  - Improvements in surgical technique and advances in myocardial protection have
      resulted in low rates of morbidity and mortality despite a greater incidence of
      high-risk patients. Noncardiac morbidity prolongs hospital stays and increases
      the costs of cardiac surgery. This study examines the preoperative predictors of
      stroke following isolated coronary bypass surgery. The clinical records of 3910
      consecutive patients who underwent isolated coronary bypass surgery at the
      University of Toronto were reviewed. Stepwise logistic regression identified six
      independent predictors of stroke following CABG (percent in parentheses) and
      calculated factor adjusted odds ratios (OR) for each risk factor. Triple vessel
      coronary artery disease was the most important predictor (1.9%, OR 5.71),
      followed by normothermic systemic perfusion (3.8%, OR 4.85), age > 70 years
      (3.2%, OR 3.88), a previous history of transient ischemic attacks or stroke prior
      to surgery (6.1%, OR 3.7), peripheral vascular disease (4.7%, OR 2.77), and
      diabetes mellitus (2.6%, OR 2.01). The mechanism of stroke is likely different
      between these high-risk groups and strategies to prevent postoperative stroke
      should focus on the mechanisms responsible in high-risk patients.

PMID- 7579845
TI  - Neurological outcomes and cardiopulmonary temperature: a clinical review.
AB  - All available controlled studies of warm versus cold and antegrade versus
      retrograde delivery of cardioplegia were reviewed to assess the incidence of
      perioperative stroke and adverse neuropsychological outcomes. Nine randomized
      trials and substudies and two studies with immediate historical consecutive
      controls reported neurological outcomes and were described as warm versus cold.
      Pooled event rates for perioperative stroke were 1.5% for warm antegrade, 3.14%
      for warm retrograde, 1.7% for cold antegrade, and 0% to 1.2% for cold retrograde.
      Examining within trial differences, only one study showed a significant
      disadvantage to warm 4.5% versus cold 1.4% on incidence of perioperative stroke,
      but the design does not permit determination of whether the difference is due to
      systemic temperature, retrograde coronary perfusion, or other factors.
      Furthermore, if only warm (> 33 degrees C) versus cold (< 30 degrees C) systemic
      perfusion is examined in all studies for the incidence of stroke irrespective of
      cardioplegia temperature or antegrade versus retrograde coronary perfusion (warm
      2.1%; cold 1.6%), the above study remains a significant outlier. This suggests
      that the differences found are unlikely to be due to temperature but may be
      related to antegrade versus retrograde coronary perfusion. Review of randomized
      trials evaluating neuropsychological function post-cardiopulmonary bypass (post
      CPB) also failed to reveal any advantage related to temperature of systemic
      perfusion. Since manipulations that are most likely to give rise to cerebral
      embolization are uniformly carried out at normothermia at the beginning and end
      of the operation, it is not entirely unexpected that the incidence of
      neurological events was found to be independent of the temperature of
      CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7579846
TI  - The management of temperature during cardiopulmonary bypass: effect on
      neuropsychological outcome.
AB  - Laboratory studies demonstrate that mild degrees of brain cooling (2 degrees C to
      5 degrees C) confer substantial protection from ischemic brain injury, and that
      mild elevation of brain temperature can be markedly deleterious. During
      hypothermic cardiopulmonary bypass (CPB) patients are made hypothermic and then
      rewarmed at a time when they are exposed to neurological insults. Our studies
      show that during rewarming, peak brain temperatures near 39 degrees C often are
      achieved inadvertently. We hypothesize that maintaining brain temperature < or =
      34 degrees C during and after CPB will reduce the incidence of postoperative
      neuropsychological deficits. We present safety data from a study of 30 patients
      assigned either to conventional hypothermic CPB with rewarming or a protocol
      where brain temperature is raised only to 34 degrees C at the time of separation
      from CPB. There was no difference in bleeding, cardiac morbidity, or time to
      extubation between groups. We designed a neuropsychological test battery to
      detect postoperative neuropsychological deficits and tested its usefulness in a
      preliminary sample of 15 patients undergoing hypothermic CPB. We found patient
      acceptability and compliance were good. Sensitivity also seemed adequate in that
      30% of patients were identified as having deteriorated at 1 week postoperatively
      compared to preoperatively, a result similar to that reported by others. Clinical
      trials of the efficacy of mild hypothermia in modulating brain injury in humans
      are needed before techniques of CPB can be designed to optimize neuroprotection.

PMID- 7579847
TI  - A critical assessment of neurological risk during warm heart surgery.
AB  - A prospective randomized trial comparing retrograde warm blood cardioplegia with
      cold oxygenated crystalloid cardioplegia in coronary bypass patients at Emory
      University revealed an increased risk of adverse neurological events in the warm
      group (4.5% vs 1.4%, p < 0.005). Multivariant analysis found four variables to be
      independent predictors of adverse neurological outcome: congestive heart failure
      (p = 0.002); age (p = 0.002); aortic cross-clamp time (p = 0.02); and
      randomization to the warm group (p = 0.026). In Toronto, a prospective randomized
      trial compared antegrade warm blood cardioplegia with antegrade cold blood
      cardioplegia. Compared to the Emory trial, the Toronto series contained fewer
      female patients (16% vs 25%), fewer patients older than age 70 (16% vs 30%), and
      fewer redo operations (4% vs 14%). The other prominent differences between the
      Emory series and the Toronto series were: extensive use of retrograde
      cardioplegia in the Emory series; mild hypothermia in the warm group in the
      Toronto series; and elevated serum glucose in the warm group in the Emory series.
      The Toronto series showed no difference in adverse neurological events comparing
      cold versus warm cardioplegia groups. A comparison of these two series suggests
      that mild hypothermia in the Toronto series, elevated glucose in the Emory
      series, or the use of retrograde cardioplegia may be operative in the elevated
      incidence of adverse neurological events seen in the Emory series in addition to
      a relatively larger number of high-risk patients (female, elderly, and redo) in
      the Emory series.

PMID- 7579848
TI  - Does cardiopulmonary bypass temperature correlate with postoperative central
      nervous system dysfunction?
AB  - A National Institutes of Health-funded trial of perfusate temperature and
      neurological function was begun in the Baystate Medical Center in February 1994.
      It randomizes patients having coronary revascularization to three temperatures-
      warm (37 degrees C), tepid (32 degrees C), and cold (20 degrees C)--for systemic
      perfusate and blood cardioplegia temperature at 37 degrees C warm, 32 degrees C
      tepid, and 6 degrees C to 10 degrees C cold. The goal is to have a quantitated
      neurological examination performed prior to operation, prior to discharge at day
      3 or 4, and at a 1-month follow-up interval. The initial 51 patients completing a
      1-month follow-up broke down to 14 cold, 22 tepid, and 15 warm. The neurological
      examination quantitated their performance on the Mathew Scale, an ordinal measure
      from 1 to 100, with 100 being normal. There was a significant (p < 0.05) decrease
      across the entire study from preoperative to postoperative that was no longer
      present at late follow-up. Although the lowest mean scores (94.8) occurred in the
      warm group, they were not statistically different from the other groups', and
      there was no discernible influence of temperature on neurological function.
      Additional patients will be entered to validate a difference if such exists.

PMID- 7579849
TI  - The effect of the single aortic cross-clamp technique on cardiac and cerebral
      complications during coronary bypass surgery.
AB  - Cardiac and cerebral events during coronary artery bypass graft (CABG) surgery
      remain a major cause of morbidity and mortality. Efforts made to reduce these
      events will have a significant impact on CABG results. The objective of this
      study was to examine our results in 394 patients undergoing primary CABG using
      the single clamp technique that probably has better myocardial and cerebral
      protective properties than the conventional technique of partial aortic
      occlusion. Age range was 35 to 88, mean of 66 years, and 168 (43%) were > or = 70
      years of age; 121 (31%) were females, 118 (30%) were diabetic, 339 (82%) were in
      New York Heart Association Functional Class III or IV, 77 (20%) had a
      preoperative intra-aortic balloon pump, 213 (54%) were nonelective, 293 (75%) had
      three vessel disease, and 55 (14%) had critical left main coronary artery
      stenosis. Antegrade crystalloid cardioplegia was used in the majority of
      patients, and the distal and proximal anastomoses were sequentially constructed
      during a single period of total aortic occlusion. The mean number of grafts was
      3.5, and 339 (86%) had > or = 3 grafts; at least one internal mammary artery was
      used in 346 (88%), a sequential vein or mammary artery in 181 (46%), and 55 (14%)
      had at least one coronary endarterectomy. The mean cross-clamp time, bypass time,
      and time to wean off bypass were 63, 83, and 20 minutes, respectively. The
      overall operative mortality was 11 of 394 (2.8%), a myocardial infarction/low
      cardiac output state occurred in 19 (4.8%), and a stroke in 3 (0.8%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7579851
TI  - New directions in the treatment of heart failure: some paradoxical observations.
AB  - The alpha-agonist drug phenylephrine has been generally considered to be
      contraindicated in patients with heart failure for the reason that increased
      afterload produced by the vasoconstriction should decrease ventricular function;
      the beta-adrenergic blocking drugs generally have been considered to be
      contraindicated in heart failure because of the dependence of the failing heart
      on beta-sympathetic agonism; the angiotensin converting enzyme inhibitors have
      been indicted recently as causing undesirable cardiovascular depression in
      patients for coronary artery bypass surgery. Yet recently, phenylephrine has been
      shown to have positive cardiac inotropic effects in a variety of experimental
      preparations including intact humans; the beta-adrenergic blocking drugs have
      been shown to be therapeutically effective in treating patients with chronic
      congestive heart failure (CHF); and the "gold standard" for treating chronic CHF
      at present are the ACEI. Consequently, the clinician caring for patients with
      cardiac disease needs to reevaluate the use of classic drugs whose original
      pharmacological properties may either have changed because of advances in
      technology or may be producing effects that were unanticipated previously.

PMID- 7579850
TI  - Jugular bulb saturation and mixed venous saturation during cardiopulmonary
      bypass.
AB  - Systemic venous oxygen saturation is clinically used as an indicator of a
      satisfactory oxygen supply demand balance on cardiopulmonary bypass (CBP).
      Cerebral desaturation has been associated with postoperative cognitive
      dysfunction and has an incidence of 17% to 23% on bypass. We tested the
      hypothesis that systemic venous saturation did not correlate with jugular bulb
      venous saturation. Blood was drawn from the radial artery, jugular bulb catheter,
      and venous return line for determination of pH, oxygen tension and saturation,
      and carbon dioxide tension at four times during bypass: warm 1 (following
      initiation of CPB); cold 1 (stable hypothermia); cold 2 (hypothermia prior to
      rewarm); and warm 2 (nasopharyngeal temperature 36 degrees C to 37 degrees C).
      Correlations of jugular bulb and systemic venous saturation at cold 1 were r =
      0.29, r2 = 0.08, and p = 0.0005, and at warm 2 were r = 0.22, r2 = 0.05, and p =
      0.007. We conclude that systemic saturation is a poor indicator of cerebral
      saturation. The poor association of jugular and systemic pump venous saturations
      underscores our inability to evaluate adequacy of cerebral perfusion. Jugular
      saturation is lower than pump venous return blood, especially at times of lower
      oxygen delivery, thus either continuous invasive or noninvasive evaluation of
      cerebral oxygenation is required to evaluate the adequacy of cerebral perfusion.

PMID- 7579852
TI  - Flow characteristics of aortic cannulae.
AB  - Atheroembolism from the ascending aorta is an emerging cause of noncardiac
      complications after open heart surgery. We designed a new arterial cannula
      specifically to reduce the exit force and velocity of blood flow, thereby
      reducing the "sandblasting" effect of the exiting blood jet. The cannula has a
      closed tip and an internal cone that diffuses blood flow such that it enters the
      aorta via multiple side holes. Fluid dynamics of the cannula were tested against
      five frequently used cannulae: Sarns High-Flow (3M Sarns High-Flow, Ann Arbor,
      MI, USA), DLP 83024 (DLP Inc., Grand Rapids, MI, USA), RMI ARS 024C (Research
      Medical Inc. of Research Industries Corp., Midvale, UT, USA), Bard 1966 (C.R.
      Bard Inc., Haverhill, MA, USA), and Argyle THI (Sherwood Medical Co. Sub American
      Home Products Corp., St. Louis, MO, USA). All cannulae had an 8.0-mm external
      diameter. The new cannula demonstrated a similar pressure drop and internal tip
      diameter as the others. The exit force (newtons) of the Soft Flow cannula was
      significantly less than the Sarns High-Flow (p < 0.05), DLP (p < 0.001), RMI (p <
      0.01), Bard (p < 0.001), and the Argyle (p < 0.001) cannulae. Peak velocity
      (cm/s) of the Soft Flow cannula was significantly less than the DLP (p < 0.01),
      RMI (p < 0.01), Bard (p < 0.01), and Argyle (p < 0.001). The cannulae all had
      similar hemolysis rates. The new arterial cannula produced the lowest exit force
      and flow velocity with no increase in hemolysis and may help to decrease the
      incidence of atheroemboli and its sequelae.

PMID- 7579853
TI  - Myocardial ischemia after cardiopulmonary bypass.
AB  - Intraoperatively, myocardial ischemia is more common after cardiopulmonary bypass
      (CPB) than before CPB. Ischemia associated with coronary vasospasm and thrombosis
      may be much more common toward the end of surgery and early in the postoperative
      period than previously appreciated. This may be because the coagulation system is
      altered during CPB, and the coronary endothelium is damaged significantly as a
      result of cardioplegic arrest followed by reperfusion. In this milieu, vasospasm
      and thrombosis may be caused by the administration of protamine. Some of the
      ischemia observed in this period actually is not reversible and is associated
      with myocardial injury and infarction. It may be ameliorated by the
      administration of calcium channel blockers, aspirin, and anticoagulants.
      Electrocardiography may be the most suitable modality for the detection of
      ischemia after CPB and postoperatively. During this period, many episodes of ST
      deviation are of a nonischemic etiology, and the ECG needs careful
      interpretation. Transesophageal echocardiography is suitable for use
      intraoperatively and early on in the intensive care unit.

PMID- 7579854
TI  - A glimpse of pre-MEDLINE literature: what's really new?

PMID- 7579855
TI  - Endovascular graft placement in experimental dissection of the thoracic aorta.
AB  - PURPOSE: To test the effectiveness of endoluminal exclusion of the false lumen in
      experimental thoracic aortic dissection by occlusion of the entry site with a
      balloon-expandable endograft. MATERIALS AND METHODS: Thoracic aortic dissections
      were induced surgically in six beagles. The endograft consisted of an ultrathin,
      12-mm-wide polyester tube sutured over a Strecker stent that was already crimped
      onto an angioplasty balloon. Fluoroscopic and intravascular ultrasonographic
      (IVUS) guidance were used. Endografts were introduced by means of femoral
      arteriotomy, via a 12-F sheath positioned in the aorta, and were then expanded on
      the angioplasty catheter. RESULTS: IVUS and aortography showed an extensive
      thoracic dissection in all animals. Only four of six endografts were successfully
      placed. At 1 month, all thoracic endografts were patent, but the false lumen was
      never thrombosed. IVUS scans demonstrated a malpositioned endograft in two cases
      and persistent reentry in all cases. CONCLUSION: Endovascular grafting of the
      aorta was feasible in experimental thoracic aortic dissection, but thrombosis of
      the false lumen was not achieved.

PMID- 7579857
TI  - Influence of anatomic distribution of atherosclerosis on the outcome of
      revascularization with iliac stent placement.
AB  - PURPOSE: To determine the influence of clinical and angiographic variables,
      including the anatomic disease pattern, on the outcome of iliac stent placement.
      PATIENTS AND METHODS: The 455 patients of the study population were divided in
      three groups according to the anatomic distribution of their peripheral
      atherosclerosis lesions. Pattern type 1 (focal aortoiliac and/or common iliac
      lesion) included 180 patients (39.6%), type 2 (external iliac lesion) comprised
      58 patients (12.8%), and type 3 (multilevel lesions) included 217 patients
      (47.7%). RESULTS: Complete relief of symptoms immediately after revascularization
      was observed in 88.3% and 85.4% of patients with pattern type 1 and 2,
      respectively, compared to 60.1% with type 3 (P < .05). The persistence of
      clinical benefit at 36-month follow-up was 91.6%, 97.9%, and 60.8% in disease
      patterns 1, 2, and 3, respectively. The overall 1-year mortality rate was 3% with
      type 1 lesions, 5.7% with type 2, and 9.7% with type 3. On multivariate logistic
      regression, the presence of a disease pattern type 3 was the most powerful
      indicator (P < .001) of early unsatisfactory clinical outcome in iliac stent
      placement. Unexpectedly, female gender was predictive of unsatisfactory clinical
      outcome (P < .01) and higher periprocedural complications (P < .001) following
      iliac stent revascularization. CONCLUSIONS: Pattern type classification helps
      identify patients at higher risk for cardiovascular morbidity and mortality.
      Ideal candidates for iliac stent placement are patients with pattern type 1 or 2
      disease.

PMID- 7579856
TI  - Endovascular repair of an internal iliac artery aneurysm with use of a stented
      graft and embolization coils.

PMID- 7579860
TI  - Removal of a ruptured angioplasty balloon catheter with use of a nitinol goose
      neck snare.

PMID- 7579858
TI  - Hepatic artery angioplasty after liver transplantation: experience in 21
      allografts.
AB  - PURPOSE: To assess whether percutaneous transluminal angioplasty (PTA) can help
      prolong allograft survival and improve allograft function in patients with
      hepatic artery stenosis after liver transplantation. PATIENTS AND METHODS:
      Hepatic artery PTA was attempted in 19 patients with 21 allografts over 12 years.
      The postangioplasty clinical course was retrospectively analyzed. Liver enzyme
      levels were measured before and after PTA to determine if changes in liver
      function occurred after successful PTA. RESULTS: Technical success was achieved
      in 17 allografts (81%). Retransplantation was required for four of 17 allografts
      (24%) in which PTA was successful and four of four allografts in which PTA was
      unsuccessful; this difference was significant (P = .03). Two major procedure
      related complications occurred: an arterial leak that required surgical repair
      and an extensive dissection that necessitated retransplantation 14 months after
      PTA. Hepatic failure necessitated repeat transplantation in seven cases from 2
      weeks to 27 months (mean, 8.4 months) after PTA. Six patients died during follow
      up, three of whom had undergone repeat transplantation. Markedly elevated liver
      enzyme levels at presentation were associated with an increased risk of
      retransplantation or death regardless of the outcome of PTA. CONCLUSION: PTA of
      hepatic artery stenosis after liver transplantation is relatively safe and may
      help decrease allograft loss due to thrombosis. Marked allograft dysfunction at
      presentation is a poor prognostic sign; thus, timely intervention is important.

PMID- 7579861
TI  - Creation of compression gastroenterostomy by means of the oral, percutaneous, or
      surgical introduction of magnets: feasibility study in swine.
AB  - PURPOSE: The use of magnets placed surgically, percutaneously, and orally to
      create compression gastroenteric anastomoses was evaluated in 11 swine. MATERIALS
      AND METHODS: Disc-shaped, jacketed rare-earth magnets with cutting edges varying
      in diameter from 0.250 inch (6.4 mm) to 0.500 inch (12.7 mm) were used in seven
      swine, and rectangular types were used in three swine. Magnets were implanted
      surgically in five and introduced by means of standard interventional techniques
      through a gastrostomy in two and perorally in four animals. Anastomoses (n = 8)
      were studied grossly and histologically for acute changes at 5-13 days and for 30
      day patency in one. RESULTS: Of the nine surviving pigs, there were seven
      completely patent anastomoses and one partially patent anastomosis at 7-13 days.
      At 5 days the anastomosis was not patent in the remaining animal. One anastomosis
      became occluded at 30 days. There was no anastomotic leakage, infection, or
      bleeding. CONCLUSIONS: Leak-free gastrojejunostomies can be created by inserting
      magnets perorally, percutaneously, or surgically.

PMID- 7579859
TI  - Synchronous embolization of the gastroduodenal artery and the inferior
      pancreaticoduodenal artery in patients with massive duodenal hemorrhage.
AB  - PURPOSE: To assess the efficacy and safety of synchronous embolization of the
      gastroduodenal artery (GDA) and inferior pancreaticoduodenal artery (IPDA) in
      patients with massive duodenal hemorrhage. PATIENTS AND METHODS: All cases of
      synchronous embolization of the GDA and IPDA at the authors' hospital between
      1980 and 1989 were retrospectively reviewed. RESULTS: Bleeding was successfully
      controlled acutely in all six patients who underwent synchronous embolization.
      Clinical evidence of recurrent hemorrhage was found in two patients, but repeat
      angiography showed no extravasation of contrast material. Three patients died
      within 30 days of embolotherapy. In one patient who also received an infusion of
      vasopressin, postmortem evidence of pancreatic necrosis was found. CONCLUSION:
      Synchronous embolization of the GDA and IPDA can be an effective treatment for
      continuing duodenal hemorrhage after failed endoscopic therapy in patients
      considered a poor surgical risk. The procedure should be undertaken only as a
      lifesaving measure due to the risk of pancreatic and duodenal necrosis.

PMID- 7579862
TI  - Evaluation of compression cholecystogastric and cholecystojejunal anastomoses in
      swine after peroral and surgical introduction of magnets.
AB  - PURPOSE: To assess the efficacy of rare-earth magnets for creating a
      cholecystogastrostomy (CG) or cholecystojejunostomy (CJ) in nine swine. MATERIALS
      AND METHODS: Neodymium-iron-boron magnets or rare-earth cobalt magnets of various
      configuration and strength were coupled in pairs to form four CGs and five CJs.
      Magnets were implanted surgically in the gallbladder and jejunum, and perorally
      in the stomach. Gross and histologic examinations of anastomoses were performed 8
      16 days later. RESULTS: All anastomoses showed good adhesion with no leakage and
      minimal inflammation. Anastomoses were fully patent in four CJs and one CG (mean,
      12 days), partially patent in one CJ and one CG (mean, 15 days), and not patent
      in two CGs. Best results were noted with jacketed disc magnets with cutting rims
      and a 400-600-g pull. The rare-earth magnets were significantly weakened by gas
      sterilization in the first four CG experiments. Two of four magnets used in CJ
      were retained despite a fully patent anastomosis. CONCLUSION: Leak-free patent or
      partially patent cholecystenteric anastomoses were created by magnet compression
      in 9-16 days. This technique may have clinical interventional applications.

PMID- 7579863
TI  - Chemical ablation of the gallbladder: is it feasible?
AB  - PURPOSE: Transcatheter ablation of the gallbladder has been attempted in animals
      and humans with a variety of chemical and physical agents. Initial in vitro
      experiments suggested sodium hydroxide and hydrogen peroxide were more effective
      sclerosants than previously reported chemical agents. A phase I trial of
      escalating concentrations of and exposure times to these agents was performed in
      vivo. MATERIALS AND METHODS: Fourteen domestic pigs underwent cholecystostomy
      tube placement and cystic duct ligation. Two weeks later, sclerosis was performed
      with sodium hydroxide/ethanol solutions and hydrogen peroxide. RESULTS:
      Sequential 15- or 30-minute exposures to 0.1 N solutions of sodium hydroxide in
      ethanol followed by 3% peroxide failed to completely eliminate the pig
      gallbladder epithelium in vivo; 0.5 N and 1.0 N sodium hydroxide in ethanol
      caused gross gallbladder hemorrhage, mural dissection, and one perforation.
      Although the gallbladder lumen was ablated, the gallbladder epithelium was not
      completely eliminated in any animal. CONCLUSION: Chemical ablation of the pig
      gallbladder epithelium was not feasible in this experimental model.

PMID- 7579865
TI  - Venous stent placement as an adjunct to the staged, multimodal treatment of Paget
      Schroetter syndrome.

PMID- 7579867
TI  - Percutaneous use of the Fogarty adherent clot catheter.

PMID- 7579864
TI  - Percutaneous thoracic duct cannulation: feasibility study in swine.
AB  - PURPOSE: To assess the feasibility of percutaneous catheterization of the
      thoracic duct (TD) in 15 pigs. MATERIALS AND METHODS: After opacification of the
      cisterna chyli (CC) with pedal lymphography, the CC is punctured transabdominally
      with a 21-gauge needle and the TD is catheterized with a 3-F catheter over a
      guide wire. For retrograde TD catheterization, the guide wire is advanced
      cephalad to a neck vein, snared, retrieved through the jugular or femoral vein,
      and used to insert a catheter retrogradely through the lymphovenous junction. The
      transabdominal wire is removed. RESULTS: Of 15 pigs studied, successful TD
      catheterization was performed in 13 (antegrade [n = 4], antegrade-retrograde [n =
      9]). Two failures were due to CC anomalies. No acute complications were noted. A
      marker was left in the CC, and TD catheterization was repeated in two pigs, 2 and
      5 days later. CONCLUSIONS: Percutaneous transabdominal TD catheterization in the
      swine is feasible, safe, and repeatable. This technique has potential clinical
      applications in organ transplantation and management of TD laceration.

PMID- 7579866
TI  - Recombinant tissue plasminogen activator for the treatment of lower extremity
      peripheral vascular occlusive disease.
AB  - PURPOSE: Regional thrombolysis in the recanalization of peripheral vascular
      occlusive disease is an increasingly accepted therapeutic modality. Efficacy and
      complication rate are major issues in thrombolytic therapy. This prospective
      study was undertaken to determine if locally delivered recombinant tissue
      plasminogen activator (r-TPA) is safe and effective in clot lysis at non-weight
      adjusted doses. PATIENTS AND METHODS: Twenty patients (undergoing 21 infusions)
      from two centers underwent fibrinolytic therapy with use of r-TPA, at a dose rate
      of 2 mg/h. The mean duration of arterial occlusion was 27.2 days (range, 1-117
      days). Concomitant intravenous heparin anticoagulation was administered to all
      patients. A coaxial infusion delivery system was employed. Hematologic parameters
      and angiographic follow-up were evaluated at 4-hour intervals during thrombolytic
      infusion. The chosen maximum r-TPA dose of 40 mg could be extended at
      investigator discretion. RESULTS: Complete clot lysis was achieved in 18 of 21
      (85.7%) infusions at a mean total dose of 38.9 mg (range, 8-84 mg). The mean
      infusion duration was 19.7 hours. In 16 of 19 (84.2%) infusions, in which the
      nadir fibrinogen level was recorded, it remained greater than 65% of baseline.
      Three of 21 (14.3%) infusions resulted in three major bleeding complications, one
      of which resulted in death. CONCLUSION: In this two-center trial, catheter
      directed r-TPA infusion at 2 mg/h is effective for clot lysis. When combined with
      concomitant heparin administration, this treatment may result in an unacceptably
      high frequency of bleeding complications.

PMID- 7579868
TI  - Renal vein thrombolysis with selective simultaneous renal artery and renal vein
      infusions.

PMID- 7579870
TI  - Accuracy of DSA in the evaluation of patency of infrapopliteal vessels.
AB  - PURPOSE: To evaluate the accuracy of intraarterial digital subtraction
      angiography (DSA) in the demonstration of patent infrapopliteal vessels. PATIENTS
      AND METHODS: One-hundred sixty-five arteriograms were obtained in 153 consecutive
      patients prospectively enrolled to evaluate lower extremity ischemia. In 86 cases
      a follow-up angiogram of the infrapopliteal vessels was obtained during surgery
      or after endovascular intervention (n = 57). Twenty-nine arteriograms were
      followed by surgical exploration of the infrapopliteal vessels. Standard
      angiographic technique was performed with intraarterial DSA of the most
      symptomatic foot. Visualization of distal vessels was compared with
      intraoperative or postintervention imaging or with the results of surgical
      exploration. RESULTS: Of the 57 procedures after which either intraoperative or
      post-endovascular intervention angiography was performed, DSA results were
      equivalent in 47 (82%) and worse in five (9%). When individual vessels were
      evaluated, the sensitivity of DSA in the identification of patent named vessels
      was 95%, and the specificity was 92%. Among 29 cases with a surgical standard of
      reference, 28 patients underwent bypass to a vessel correctly identified as
      patent at DSA; one patient was incorrectly identified as having no patent named
      vessels. CONCLUSION: Intraarterial DSA is accurate and reliable in the assessment
      of patency in infrapopliteal vessels before surgery or endovascular intervention
      in patients with infrainguinal atherosclerotic disease.

PMID- 7579871
TI  - Interpretations and treatment decisions based on MR angiography versus
      conventional arteriography in symptomatic lower extremity ischemia.
AB  - PURPOSE: To determine the frequency with which treatment plans based on findings
      at magnetic resonance angiography (MRA) match those based on findings at
      conventional x-ray arteriography (XRA) in the evaluation of symptomatic lower
      extremity ischemia. PATIENTS AND METHODS: Two-dimensional time-of-flight (TOF)
      MRA was performed in 42 patients undergoing XRA for evaluation of symptomatic
      lower extremity ischemia. The blind interpretations and treatment plans based on
      MRA findings were compared with those based on XRA findings, with use of XRA as
      the standard of reference. RESULTS: For identification of hemodynamically
      significant stenosis or occlusion, the sensitivity and specificity of MRA was
      100% and 23% for iliac segments, 100% and 82% for common femoral segments, 89%
      and 67% for superficial femoral segments, 100% and 88% for popliteal segments,
      and 92% and 91% for tibioperoneal segments, respectively. The treatment plan
      based on MRA findings matched that based on XRA findings in 41% of patients.
      CONCLUSION: For evaluation of symptomatic lower extremity ischemia, two
      dimensional TOF MRA cannot be considered a reliable substitute for XRA in
      patients who lack contraindications to XRA.

PMID- 7579872
TI  - Osteochondroma: an unusual cause of vascular disease in young adults.
AB  - Vascular complications such as pseudoaneurysm, arterial thrombosis, luminal
      stenosis due to extrinsic compression, deep venous thrombosis, and arteriovenous
      fistula are known complications of osteochondroma. The authors describe three
      cases of vascular injury caused by osteochondroma: popliteal artery impingement,
      popliteal artery pseudoaneurysm formation, and superficial femoral artery
      pseudoaneurysm with peripheral occlusion of the tibial and peroneal arteries due
      to embolization. Fifty-six cases of vascular complications due to osteochondroma
      from the English literature are also reviewed. This entity should be considered
      in young patients with evidence of peripheral vascular insufficiency or in
      patients with known osteochondroma who develop symptoms of local pain and
      swelling in the involved extremity.

PMID- 7579873
TI  - Progressive arteriocolonic fistulization following pelvic irradiation.

PMID- 7579869
TI  - Percutaneous management of suppurative pylephlebitis.

PMID- 7579877
TI  - New self-expandable spiral metallic stent: preliminary clinical evaluation in
      malignant biliary obstruction.
AB  - PURPOSE: To describe a new self-expandable spiral-shaped metallic stent and to
      evaluate its clinical efficacy in malignant biliary obstructions. PATIENTS AND
      METHODS: The stent was made of a 0.01-inch (0.25-mm) stainless steel wire bent in
      a zigzag pattern and was formed into a spiral configuration by differing the
      length of legs on each bend. One revolution was composed of 10 bends, and the
      stent was longitudinally connected by hanging each bending point of abutting
      bends, without use of suture or silver solder. Twenty-six stents were placed to
      relieve malignant biliary obstruction in 18 patients. Follow-up of 5-11 months
      (mean, 7 months) was obtained. RESULTS: All stents were placed in the desired
      location, and no procedural complications were encountered. Within 1 week after
      placement, all stents regained 90% or more of their original diameters. Five
      patients died (range, 5-36 weeks), and 13 patients are still alive (range, 20-45
      weeks). Two patients experienced recurrent jaundice and underwent further
      treatment. The stent was easily inserted, expanded well, was flexible, could be
      repositioned, and did not shorten. CONCLUSION: Favorable clinical results were
      obtained with this spiral stent in malignant biliary obstruction, and further
      clinical testing is warranted.

PMID- 7579874
TI  - The first rib as a fluoroscopic marker for subclavian vein access.
AB  - PURPOSE: To determine whether the anatomic relationship between the subclavian
      vein (SCV) and the first rib is sufficiently constant to allow safe and
      reproducible fluoroscopically guided SCV puncture. MATERIALS AND METHODS: Forty
      four subclavian venograms were obtained from 42 consecutive adult patients.
      Position and width of the SCV crossing over the first rib were recorded by using
      radial coordinates. Based on this anatomic study, 42 SCV access procedures were
      performed with use of the first rib as a fluoroscopic marker. Technical success,
      complications, number of 21-gauge needle passes, physician experience, and
      patients' body habitus were recorded. RESULTS: Mean angular position of SCV/first
      rib crossover was 94.7 degrees (standard deviation [SD], 7.42 degrees). Mean
      radial width of the SCV was 14.9 degrees (SD, 3.1 degrees). On 25 of the 44
      subclavian venograms (60%), the SCV/first rib crossover lay within the 90 degrees
      99 degrees segment, and on 36 of 44 (82%) it lay within the 85 degrees-104
      degrees segment. Technical success in accessing the SCV was 100% (42 of 42
      procedures). Two minor complications involved subclavian artery puncture with the
      21-gauge needle without sequelae. The mean number of needle passes required was
      2.86 (median, 1.7). There was no correlation between needle passes and patients'
      body habitus or physician experience. CONCLUSION: The SCV is reliably constant in
      its relation to the first rib. The first rib alone provides a reliable
      fluoroscopic marker for safe SCV access without the need for ultrasound guidance
      or peripheral contrast material administration.

PMID- 7579875
TI  - Functional restoration of occluded central venous catheters: new interventional
      techniques.

PMID- 7579878
TI  - Renal biopsy with forceps through the femoral vein.
AB  - PURPOSE: To evaluate the usefulness of a new technique of transvascular renal
      biopsy with a flexible forceps in high-risk patients and compare its results with
      those reported for other techniques of renal biopsy. PATIENTS AND METHODS:
      Sixteen transfemoral renal biopsies were performed in 13 high-risk patients.
      Indications included severe bleeding disorders, combined renal-hepatic biopsy,
      morbid obesity, solitary kidney, and poor clinical condition. The technique was
      performed through the femoral vein; a 7-F Mullins introducer sheath was placed in
      a subcortical renal vein, and the biopsy was performed with a flexible biopsy
      forceps. RESULTS: Renal tissue was obtained in 15 of 16 procedures (93.7%) with
      at least one glomerulus in 14 of 16 (87.5%), and at least six glomeruli in 11 of
      16 procedures (69%). Samples adequate for diagnosis were obtained in 13 of 16
      procedures (81%). Mean number of glomeruli per procedure was 12.6 (range, 0-39).
      Aside from transient hematuria in two patients, no other complications were known
      to have occurred. CONCLUSIONS: Transfemoral renal biopsy is a safe technique for
      acquisition of renal samples in high-risk patients. The procedure can be
      performed at the same time as other vascular techniques. The histopathologic
      results, although worse than those obtained with the percutaneous approach, are
      better than those reported with other transvascular techniques.

PMID- 7579876
TI  - Percutaneous cholecystostomy for the diagnosis and treatment of acute calculous
      and acalculous cholecystitis.
AB  - PURPOSE: To determine the safety, efficacy, and diagnostic utility of
      percutaneous cholecystostomy in patients with suspected calculous or acalculous
      cholecystitis. PATIENTS AND METHODS: Percutaneous cholecystostomy guided with
      ultrasound (US) was performed in 58 consecutive hospitalized patients with
      suspected acute cholecystitis (28 with calculous, 30 with acalculous disease) who
      were not surgical candidates. RESULTS: The gallbladder was successfully
      catheterized in all 58 patients; 48 patients (83%) had a final diagnosis of acute
      cholecystitis. Clinical benefit was seen in 26 of 28 patients (93%) with
      calculous cholecystitis and in 16 of 20 patients (80%) with acalculous disease.
      The six patients who did not respond had pathologic evidence of transmural
      inflammation, and five had a gangrenous wall. The gallbladder was excluded as the
      source of sepsis in 10 patients with suspected acalculous cholecystitis. These
      patients' conditions did not improve after percutaneous cholecystostomy. Of the
      48 patients with cholecystitis, 18 underwent cholecystectomy, 25 recovered and
      had their catheters removed, and five died of other causes with their catheters
      in place. There was one major complication, and seven minor complications.
      CONCLUSION: Percutaneous cholecystostomy is efficacious in both calculous and
      acalculous cholecystitis, but it may be most useful in the diagnosis of
      acalculous cholecystitis.

PMID- 7579879
TI  - Nonoperative management of dacryolithiasis.

PMID- 7579880
TI  - Notice of duplicate publication.

PMID- 7579881
TI  - Discrepancies between data published in abstracts and data presented at the SCVIR
      annual meeting.

PMID- 7579882
TI  - Hepatic chemoembolization: are prophylactic antibiotics necessary?

PMID- 7579883
TI  - Consequences of acute closure of a decompressed portal system.

PMID- 7579884
TI  - Standardized rat genetic nomenclature.

PMID- 7579885
TI  - Mapping around the Fused locus on mouse chromosome 17.
AB  - We have established a high-resolution genetic map of the region surrounding the
      Fused locus as a first step towards the molecular identification and analysis of
      this gene. The candidate region has been covered to a large extent by YAC and P1
      contigs, and has been partly characterized by pulsed-field gel analysis.

PMID- 7579886
TI  - Low resolution mapping around the flavivirus resistance locus (Flv) on mouse
      chromosome 5.
AB  - Although the phenomenon of innate resistance to flaviviruses in mice was
      recognized many years ago, it was only recently that the genetic locus (Flv)
      controlling this resistance was mapped to mouse Chromosome (Chr) 5. Here we
      report the fine mapping of the Flv locus, using 12 microsatellite markers which
      have recently been developed for mouse Chr 5. The new markers were genotyped in
      325 backcross mice of both (C3H/HeJ x C3H/RV)F1 x C3H/HeJ and (BALB/c x C3H/RV)F1
      x BALB/c backgrounds, relative to Flv. The composite genetic map that has been
      constructed identifies three novel microsatellite loci, D5Mit68, D5Mit159, and
      D5Mit242, tightly linked to the Flv locus. One of those loci, D5Mit159, showed no
      recombinations with Flv in any of the backcross mice analyzed, indicating tight
      linkage (< 0.3 cM). The other two, D5Mit68 and D5Mit242, exhibited two and one
      recombinations with Flv (0.6 and 0.3 cM) respectively, defining the proximal and
      distal boundaries of a 0.9-cM segment around this locus. The proximal flanking
      marker, D5Mit68, maps to a segment on mouse Chr 5 homologous to human Chr 4.
      This, together with the previous data produced by our group, locates Flv to a
      region on mouse Chr 5 carrying segments that are conserved on either human Chr 4,
      12, or 7, but present knowledge does not allow precise identification of the
      syntenic element.

PMID- 7579887
TI  - Genetic map of 16 polymorphic markers forming three linkage groups assigned to
      rat chromosome 4.
AB  - Sixteen polymorphic markers, including markers for eight new loci, forming three
      linkage groups, were assigned to rat Chromosome (Chr) 4 by linkage analysis of
      the progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred
      rats. One gene, Igk, was mapped by restriction fragment length polymorphism
      (RFLP) analysis. One marker for Tcrb was identified by the polymorphic insertion
      of a repetitive LINE element. The remaining 14 markers contained polymorphic
      simple sequence repeats (SSRs). Ten were identified in genes (Tgfa, Npy, Prss1,
      Prss2, Aldr1, Iapp, Prp, Eno2, Cacnl1a1, and Il6), one was identified in a
      sequence related to a gene (Egr4l1), and three were identified in anonymous DNA
      segments. The SSR markers were highly polymorphic in 16 inbred rat strains. These
      markers expand the genetic map of the rat and should be useful in future genetic
      studies of inbred rats.

PMID- 7579890
TI  - Localization of the mouse mammary tumor provirus, Mtv44, on chromosome 11.

PMID- 7579888
TI  - Porcine SINE-associated microsatellite markers: evidence for new artiodactyl
      SINEs.
AB  - Approximately 24% (170/710) of porcine (dG-dT)n.(dC-dA)n microsatellites isolated
      in our laboratory are associated with a previously described porcine Short
      Interdispersed Element (SINE) termed PRE-1 SINE. Another 5.6% (40/710) of the
      microsatellites were adjacent to two previously unidentified SINE sequences,
      which we have designated ARE-1P (Artiodactyl Repetitive Element-1 Porcine) and
      ARE-2P. The ARE repeats were also found in bovine microsatellite and genomic
      sequences in the GenBank database. Genotypic information was obtained from 68.9%
      of primers where at least one primer sequence was obtained from the PRE-1 SINE
      and 66.6% of primer pairs designed from the ARE SINEs. The use of primers derived
      from SINEs significantly increases the number of primer pairs available for
      genetic linkage studies in swine.

PMID- 7579891
TI  - Phenotypic and physical analysis of a chemically induced mutation disrupting
      anterior axial development in the mouse.

PMID- 7579893
TI  - Comparative mapping of the proximal part of bovine chromosome 1.

PMID- 7579889
TI  - Cbx-rs2 (M31), a mouse homolog of the Drosophila Heterochromatin protein 1 gene,
      maps to distal chromosome 11 and is nonallelic to Om.

PMID- 7579892
TI  - The murine form of TXK, a novel TEC kinase expressed in thymus maps to chromosome
      5.

PMID- 7579894
TI  - Bovine desmocollin genes (DSC1, DSC2, DSC3) cluster on chromosome 24q21/q22.

PMID- 7579895
TI  - Genetic mapping of the alpha 1 and alpha 2 (IV) collagen genes to mouse
      chromosome 8.

PMID- 7579896
TI  - Genetic mapping of gene encoding the large subunit of replication factor C (A1
      p145) to mouse chromosome 5.

PMID- 7579897
TI  - Genetic mapping of the choroideremia-like, rab escort protein-2 gene on mouse
      chromosome 1.

PMID- 7579898
TI  - Regional localization of rat peripheral myelin protein 22 (Pmp22) gene to
      chromosome 10q22 by FISH.

PMID- 7579901
TI  - Comparative characterization of the fermentation pathway of Saccharomyces
      cerevisiae using biochemical systems theory and metabolic control analysis: model
      definition and nomenclature.
AB  - Mathematical tools that involve the determination of systemic responses to small
      changes in metabolites or enzymes have demonstrated their utility for analyzing
      metabolic pathways. The different methodologies based on these ideas allow for
      modeling and analyzing biochemical pathways focusing on the coordinate behavior
      of the whole system. However, one must become familiar with the difference in
      nomenclature and methodology to relate the models and results obtained by
      applying these techniques and to appreciate their potential for answering
      fundamental questions about biochemical systems. In the following three papers we
      show how this can be facilitated by comparing the nomenclature, methodology, and
      results of the two leading techniques in this area, metabolic control analysis
      and biochemical systems theory, using a model of the fermentation pathway in
      Saccharomyces cerevisiae as a reference system. In the present paper we review
      the nomenclature, technical concepts, and related experimental measurements while
      creating a practical dictionary for the reference system that makes the
      relatedness of the two approaches more apparent. In the second paper, subtitled
      Steady-State Analysis, we show that both approaches give the same picture for
      many systemic responses of the reference system. In the third paper of this
      series, subtitled Model Validation and Dynamic Behavior, we show that the quality
      of the model can be assessed by studying the sensitivity to changes in the system
      parameters. We hope to illustrate the usefulness of these tools in providing an
      interpretation of the experimental measurements in a specific metabolic pathway.

PMID- 7579899
TI  - Multipoint genetic linkage analysis of the m2 human muscarinic receptor gene.

PMID- 7579900
TI  - A mechanoreceptor model for rapidly and slowly adapting afferents subjected to
      periodic vibratory stimuli.
AB  - A simple model of Freeman and Johnson on cutaneous mechanoreceptors is modified
      by introducing mechanisms for hyperexcitation and refractoriness. These lead to
      significant improvements in the match between the neural and model data.

PMID- 7579902
TI  - Comparative characterization of the fermentation pathway of Saccharomyces
      cerevisiae using biochemical systems theory and metabolic control analysis:
      steady-state analysis.
AB  - In the preceding paper in this issue, we have shown that metabolic control
      analysis and biochemical systems theory use the same experimental information to
      describe a metabolic system. In this paper, we analyze the steady-state
      properties of this pathway by applying both methods. Our results show the
      correspondence of the steady-state characterizations and illustrate the
      relationships between the different nomenclatures used. With both approaches, we
      identify metabolite pools that are strongly influenced by changes in enzyme
      concentration when cells are immobilized at pH 5.5. In the final paper of this
      series, which follows, we discuss the need to assess the quality of a model and
      the potential difficulties that may arise if the steady-state characterization is
      accepted without testing its quality. We then validate the different models using
      parameter sensitivity concepts.

PMID- 7579903
TI  - Comparative characterization of the fermentation pathway of Saccharomyces
      cerevisiae using biochemical systems theory and metabolic control analysis: model
      validation and dynamic behavior.
AB  - In the first two papers of this series (immediately preceding, this issue), we
      characterized the steady-state properties of a model of a fermentation pathway in
      Saccharomyces cerevisiae in four experimental conditions. In each of these
      conditions, the pictures obtained by metabolic control analysis and biochemical
      systems theory were coincident, which illustrates the relatedness of the two
      approaches. In this paper we analyze the quality of this description by means of
      the tools available within biochemical systems theory, and we show that in some
      of the experimental conditions studied the system is poorly characterized. The
      most critical condition corresponds to the immobilization of the cells at pH 5.5,
      in which the kinetic characterization appears to be inaccurate. Furthermore,
      sensitivity analysis and the study of the local steady-state stability identify
      the most critical parameters. The results of these analyses are confirmed by the
      predictions of the dynamic response of the model using its S-system
      representation. This illustrates the utility of these tools and warns against
      using the steady-state characterization without testing its validity.

PMID- 7579905
TI  - The effects of sulphasalazine on male fertility.

PMID- 7579907
TI  - Induction of endometriosis in mice: a new model sensitive to estrogen.
AB  - Endometriosis consists of the growth of endometrial tissue outside the uterus. A
      rat model of endometriosis is available to evaluate the potential for
      environmental chemicals to promote the disease but may be relatively insensitive
      for the evaluation of the hazard of certain compounds. Our objective, which was
      to develop a mouse model for endometriosis, was based on (a) the promotion of
      endometriosis in primates by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), (b)
      the apparent relationship between endometriosis and immunodeficiency, and (c)
      evidence that humoral immunity is suppressed in mice but not rats following TCDD
      exposure. In the mouse model, slices of uterus were sutured to intestinal
      mesenteric vessels. By 3 weeks after surgery, these sites were cyst-like
      structures. The growth of the sites was hormone dependent. In intact mice, sites
      measured 3.60 +/- 0.22 mm; vehicle and estrone (0.5 microgram/day) treatments
      produced site diameters of 0.95 +/- 0.128 and 5.28 +/- 0.355 mm, respectively.
      This new mouse model provides a sensitive and useful technique for future studies
      of the potential for specific xenobiotics to promote the development of
      endometriosis.

PMID- 7579904
TI  - Qualitative analysis of Kolmogorov-type models of predator-prey systems.
AB  - The qualitative behaviors of Kolmogorov-type models are investigated under
      assumptions that are consistent with models of predator-prey systems and
      biologically realistic. The main purpose of this paper is to prove the
      boundedness of solutions and to give criteria for the existence of limit cycles
      for the system. In the case that the positive equilibrium is locally
      asymptotically stable, an example shows that there could be more limit cycles.
      This example serves as a counterexample to the global stability criterion of
      Huang.

PMID- 7579906
TI  - Analogous tamoxifen and estrogen effects on transforming growth factor-betas 1
      and 2 in the rat uterus.
AB  - Estrogenic stimulation is a potent risk factor for the development of uterine
      cancer. More recently, analysis of patients in prospective breast cancer trials
      have established that tamoxifen also increases uterine cancer risk. In this
      report, uteri of oophorectomized rats were examined to ascertain the effects of
      estrogen and tamoxifen on the uterine induction of two isoforms of transforming
      growth factor-beta (TGF-beta). In contrast to studies of cells derived from
      breast epithelium, our studies reveal that both estrogen and tamoxifen increase
      immunoreactive TGF-beta. These changes were particularly pronounced in the
      endometrial stroma. Effects of progesterone also were examined and found to be
      distinct and relatively restricted to the glandular epithelium. These studies
      indicate that, in the uteri of oophorectomized rats, tamoxifen exerts estrogen
      like effects on a peptide previously implicated in the control of cellular growth
      and differentiation. We hypothesize that induction of TGF-beta isoforms may be an
      important mediator of both estrogen- and tamoxifen-induced proliferative
      disorders in the uterus.

PMID- 7579908
TI  - Stability of urinary female reproductive hormones stored under various
      conditions.
AB  - Urinary reproductive hormones afford specific and sensitive evaluation of female
      reproductive potential in epidemiologic and clinical settings. The goal of this
      study was to characterize the stability of urinary luteinizing hormone, follicle
      stimulating hormone, estrone 3-glucuronide, pregnanediol 3-glucuronide, and
      creatinine during storage as functions of time, temperature, and additives. After
      2 weeks with no additives, activity of the four analytes, relative to initial
      concentrations, ranged from 91.9 to 102.8% at 4 degrees C, 35.1 to 89.6% at 25
      degrees C, and 7.5 to 66.9% at 37 degrees C. Antimicrobial additives did not
      consistently improve stability. Analyte activity for samples stored with no
      additives for 24 weeks at -80 degrees C ranged from 69.0 to 101.2%. Glycerol and
      bovine serum albumin improved analyte stability; activity ranged from 91.1 to
      106.3%. Other additives were ineffective. These results reveal conditions for
      storing reproductive hormone analytes in urine during epidemiologic field
      studies.

PMID- 7579910
TI  - Transplacental toxicity of 3-methylsulphonyl-DDE in the developing adrenal cortex
      in mice.
AB  - The transplacental transfer, irreversible binding, and ultrastructural lesions in
      the fetal adrenal cortex were studied following single injections of the
      persistent DDT-metabolite 3-methylsulphonyl-DDE (MeSO2-DDE) in pregnant C57B1
      mice. Tape-section autoradiograms of fetuses on gestation days 12 to 17 revealed
      a high and tissue-specific accumulation of MeSO2-DDE-14C-derived radioactivity in
      the fetal adrenal gland. On gestation day 12 the adrenal radioactivity could be
      extracted with organic solvents, whereas on days 13 to 17 the radioactivity in
      the adrenal was irreversibly bound and could not be extracted from the tissue. As
      determined by computer-assisted image analysis of autoradiograms, the uptake of
      radioactivity in the fetal adrenals increased continuously with gestational age.
      Electron microscopy revealed mitochondrial degeneration and vacuolation in fetal
      adrenal cortex cells following injection of MeSO2-DDE (25 mg/kg b.w.) to the
      pregnant dam. The lesions were clearly visible on days 14 to 15 but most
      pronounced on days 16 to 17. Administration of the cytochrome P450(11 beta)
      inhibitor metyrapone to pregnant dams (gestation day 17) reduced the
      mitochondrial toxicity induced by MeSO2-DDE in the fetal adrenal cortex. In
      conclusion, the adrenocorticolytic DDT metabolite MeSO2-DDE is transformed to a
      reactive, cytotoxic metabolite in the fetal adrenal cortex from its earliest
      stage of development. Hence, the activating cytochrome P450 form, previously
      proposed to be P450(11 beta), seems to be expressed during gestation days 12 to
      13 in the adrenal cortex in the mouse fetus.

PMID- 7579909
TI  - Maternal smoking inhibits early human cytotrophoblast differentiation.
AB  - Differentiation of the specialized epithelial cells of the placenta, termed
      cytotrophoblasts, is a particularly important aspect of placental development
      during the first trimester of pregnancy. During this process cytotrophoblast stem
      cells either fuse to form the syncytium or aggregate to form cell columns that
      adhere to, then invade the uterus. We found that chorionic villi from early
      gestation placentas of mothers who smoke showed a marked reduction in cell
      columns, a defect that could not be corrected by placing them in culture. We used
      two different in vitro models to determine if nicotine plays a role in the
      etiology of this defect. Exposing early gestation chorionic villi from nonsmoking
      women to nicotine inhibited subsequent cell column formation in vitro. Nicotine
      also inhibited normal first trimester cytotrophoblast invasion, apparently by
      reducing the ability of treated cells to synthesize and activate the 92 kDa type
      IV collagenase, an important mediator of invasion in vitro. These results suggest
      that maternal cigarette smoking inhibits the trophoblast differentiation pathway
      that leads to column formation and uterine invasion. This effect, which is due at
      least in part to the effects of nicotine, may contribute to the growth
      retardation observed in fetuses of mothers who smoke during pregnancy.

PMID- 7579911
TI  - Effects observed on gestational day 13 in rat embryos exposed to albendazole.
AB  - Albendazole (ABZ) was utilized as a model to investigate the pathogenesis of
      benzimidazole-induced abnormalities. Pregnant Sprague-Dawley rats were treated po
      with 0, 10, 20, and 30 mg/kg on gestational days (GD) 10 to 12. The embryos were
      examined on GD 13, as a window for observing the origin of alterations detected
      at term. Embryolethality and growth reduction showed dose-related increases at
      the three dose levels. At 10 mg/kg, an increased developmental delay of limb buds
      and a less than 5% incidence of embryos with abnormal head or shape were
      detected. At 20 and 30 mg/kg, > 20% of embryos showed morphologic alterations
      involving mainly shape abnormalities and the development of forelimb buds,
      branchial bars, eye, and telencephalon; closure of neuropores was unaffected.
      Dose-response relationships for morphologic alterations showed steeper slopes
      than for growth reduction and embryolethality.

PMID- 7579912
TI  - Interlaboratory evaluation of embryotoxicity in the postimplantation rat embryo
      culture.
AB  - The embryotoxicity of eight xenobiotic compounds in rat postimplantation whole
      embryo culture was blindly tested in four laboratories according to a standard
      protocol. The results show that the four nonteratogens amaranth, penicillin,
      isoniazid, and saccharin did not affect embryogenesis apart from general toxicity
      at very high concentrations in culture for amaranth and isoniazid. There was good
      concordance of results across the laboratories. The four teratogens (retinoic
      acid, 6-aminonicotinamide, acetylsalicylic acid, and vincristine) induced a
      variety of specific embryotoxic effects, which were in most cases similar in all
      laboratories. These results indicate that the definition for specific
      embryotoxicity used, as well as the culture duration and embryonic age are
      crucial for concordant scoring. Other methodologic differences did not
      significantly influence scoring of embryotoxicity. Therefore, within the limits
      of the end points and embryonic stage represented in the method, embryo culture
      appears as a useful method for embryotoxicity screening, which can be
      reproducibly applied in different laboratories.

PMID- 7579913
TI  - Reproductive and neurobehavioral effects of imazalil administered to mice.
AB  - The fungicide imazalil was given in the diet at levels of 0 (control), 0.012,
      0.024, and 0.048% from 5 weeks of age of the F0 generation to 9 weeks of age in
      the F1 generation in mice, and selected reproductive and neurobehavioral
      parameters were measured. Number of movements, movement time, total distance,
      number of vertical activities, number of turnings, and number of defecations
      during movement activity at 8 weeks of age of the F0 generation showed adverse
      effects of treatment on male mice. There were few adverse effects of imazalil on
      either litter size or weight and sex ratio. Average body weight of offspring
      during the early lactation period was significantly depressed in the high- and
      middle-dose groups of each sex. In the neurobehavioral parameters, surface
      righting and swimming head angle were significantly affected in male and female
      offspring during the early lactation period. The dose levels of imazalil in this
      study produced some adverse effects in reproductive and neurobehavioral
      parameters in mice.

PMID- 7579916
TI  - Testicular alterations in rats due to gestational and early lactational
      administration of lead.
AB  - A solution of lead acetate (300 mg/L) was administered via drinking water to
      pregnant Wistar rats from day 1 of pregnancy to delivery (Pb-treated day 0 group)
      or throughout gestation and early lactation (from day 1 to day 5 postnatal) (Pb
      treated day 5 group). When the pups were born, four dams and their offspring in
      each group (control day 0, Pb-treated day 0, control day 5, and Pb-treated day 5)
      were sacrificed on day 0 (day 0 groups) or on day 5 (day 5 groups). Relative
      testicular weight and gross testicular structure were not altered by the
      treatment. The seminiferous tubule diameter and the number of prospermatogonia
      were reduced by the treatment. Determination of the n-ploidy stage of
      prospermatogonia indicates that these cells have more proliferative activity in
      Pb-treated rats than in control rats. On the other hand, the total DNA, RNA, and
      protein content of the testes in treated rats was significantly reduced, but the
      DNA: RNA ratio remained unaltered.

PMID- 7579915
TI  - Testicular toxicity of the transferrin binding radionuclide 114mIn in adult and
      neonatal rats.
AB  - Adult (70 d) and neonatal (7 d) male rats were dosed (i.p.) with 37 MBq/kg (1
      mCi/kg; approximately 1 microgram elemental indium/kg) 114mIn, a transferrin
      binding radionuclide. In adults, approximately 0.25% of the injected activity
      localised within the testis by 48 h postinjection and remained constant for up to
      63 d. In neonates, 0.06% of the activity was in the testis by 48 h, and this
      declined such that by 63 d only 0.03% remained. At 63 d, treated rats had reduced
      sperm head counts and abnormal testicular histology that was more marked in
      animals dosed as adults than as neonates. In vitro, uptake of 114mIn into
      seminiferous tubules isolated from 7-, 20-, or 70-d-old rats was compared with
      that of 125I. Both radionuclides were readily accumulated by the tubules. Whilst
      114In uptake into 20- and 70-d tubules was inhibited by excess transferrin,
      uptake into 7-d tubules was unchanged. 125I uptake was not affected by excess
      transferrin. These data support the contention that some radionuclides may cross
      the blood-testis barrier by utilisation of the physiologic iron-transferrin
      pathway, which may lead to greater testicular damage in adult compared to
      neonatal animals.

PMID- 7579919
TI  - [Professional protective work clothing].

PMID- 7579914
TI  - Stage specificity of Ara-C induced carpal and tarsal bone anomalies in mice.
AB  - Pregnant mice were injected intraperitoneally with a single dose of 5 mg/kg of
      cytosine arabinoside (Ara-C) on different gestational days (dg 9-12). On the 15th
      postnatal day, skeletal anomalies of the paws were examined, and associations
      between carpal and tarsal bone anomalies and digit anomalies were assessed. The
      types of carpal and tarsal bone anomalies differed according to the time of
      exposure to Ara-C during pregnancy. It was also found that the "critical period"
      for the carpal and tarsal bones is wider than that of the digits. The occurrence
      of anomalies of phalangeal and metacarpal/metatarsal bones was always associated
      with carpal or tarsal bone anomalies, although some carpal and tarsal bone
      anomalies occurred alone. It may be that the Ara-C threshold is considerably
      lower in the carpal and tarsal bones than in the digits.

PMID- 7579917
TI  - Short-term male reproductive toxicity study with sulfasalazine in the rat.
AB  - Sulfasalazine (2-hydroxy-5-[[4-[(2-pyridinylamino) sulfonyl] phenyl]azo]benzoic
      acid; SASP) was administered to rats in a short-term male reproductive toxicity
      study to further examine the utility of this grouping of techniques and to
      generate reference data with a substance that is known to cause reversible
      infertility in men. Adult male CD rats (10/group) were orally administered 0,
      150, 300, or 600 mg SASP/kg body weight in divided doses for 14 d followed by a 2
      week period without treatment. Males were killed on test day (TD) 15 or 29. At
      each time point, the reproductive system was evaluated by comparing testicular
      and epididymal weights, DNA ploidy distributions of testicular cell suspensions,
      testicular and epididymal histopathology, and epididymal sperm concentrations,
      motion, morphology, and breakage. Adding time as a factor in the protocol aids in
      distinguishing testicular from posttesticular effects. Changes in sperm quality
      after 2 weeks of test article administration (TD 15) predominantly reflect
      effects that occurred after the sperm entered the epididymis, while testicular
      effects predominated on TD 29. Beginning on TD 14, males to be killed on TD 29
      were cohabited with untreated females (1:2). Females were killed at midgestation
      and examined for pregnancy status. Body weight gain was depressed in all SASP
      groups during the first 3 d of test article administration. Food consumption was
      depressed at the 300- and 600-mg/kg dose levels. No changes were seen in
      testicular weight, but epididymal weight was depressed at the 600-mg/kg dose
      level. DNA ploidy distributions determined by flow cytometry did not indicate
      that the kinetics of spermatogenesis were disturbed. However, alterations in
      sperm release, which have not previously been reported, were seen at all SASP
      dose levels. On TD 29, the percentage of progressively motile sperm was depressed
      and beat/cross frequency was increased at the 600-mg/kg dose level. No changes
      were observed in sperm morphology or breakage. Fertility was slightly depressed
      at the 600-mg/kg dose level. In this study, testicular histopathology provided
      the most sensitive endpoint for reproductive toxicity. The impairment of
      fertility immediately after treatment was stopped, when no changes were apparent
      in sperm release or sperm motion, suggested that decreased sperm concentrations
      and altered motility, while contributory, may not be the primary causes of SASP
      mediated infertility.

PMID- 7579918
TI  - Isolation of rat sperm from the vas deferens for sperm motion analysis.
AB  - A technique for isolation of viable spermatozoa from the rat vas deferens is
      presented. A single vas deferens from a mature Sprague-Dawley rat contains 35.4
      +/- 3.3 million spermatozoa, and a 0.5-cm segment from the distal end of the vas
      will spontaneously expel 8.96 +/- 1.39 million sperm relatively free of cellular
      debris when placed into a balanced salt solution. Treatment of rats (n = 5) with
      alpha-chlorohydrin (100 mg/kg, single dose) significantly reduced, relative to
      controls (n = 5, water 10 mL/kg), sperm motility by 72%, swimming velocity by
      44%, and head displacement motion by 50%, but did not affect the number of sperm
      in the vas deferens nor sperm recovery. In summary, the isolation of rat sperm
      from the vas deferens can be achieved with minimum handling in a manner that is
      not confounded by sperm toxicity.

PMID- 7579921
TI  - Acute toxicity of some synthetic cationic and zwitterionic surfactants to
      freshwater amphipod Echinogammarus tibaldii.

PMID- 7579922
TI  - Sublethal effects of mixtures of copper and ammonia on selected biochemical and
      physiological parameters in the catfish Heteropneustes fossilis (Bloch).

PMID- 7579923
TI  - Effects of chlorocresol (4-chloro-2-methyl phenol) administered during the
      fertilization and cleavage phases of Xenopus laevis.

PMID- 7579924
TI  - Xenobiotic metabolism by glutathione S-transferase in gill of fish from Arabian
      Gulf.

PMID- 7579920
TI  - Effects of organic and inorganic substances on the cell proliferation of L-929
      fibroblasts and Tetrahymena pyriformis GL protozoa used for toxicological
      bioassays.

PMID- 7579926
TI  - Effects of metals on the total lipid content in the gypsy moth (Lymantria dispar,
      Lymantriidae, Lepid.) and its hemolymph.

PMID- 7579928
TI  - Reciprocal influences of temperature and copper on survival of fathead minnows,
      Pimephales promelas.

PMID- 7579925
TI  - Distribution of heavy metals in tissues of the shrimp Penaeus californiensis from
      the northwest coast of Mexico.

PMID- 7579929
TI  - Toxic and genotoxic activity of water samples from the River Ljubljanica.

PMID- 7579930
TI  - Toxicity of phenolic compounds to sediment bacteria.

PMID- 7579927
TI  - Acute toxicity of selected metals and phenols on RTG-2 and CHSE-214 fish cell
      lines.

PMID- 7579931
TI  - Antimicrobial, phytotoxic, nematicidal, cytotoxic, and mutagenic activities of 1
      hydroxypyrene, the initial metabolite in pyrene metabolism by the basidiomycete
      Crinipellis stipitaria.

PMID- 7579933
TI  - Tetrachlorodibenzo-p-dioxin residue reduction by cooking/processing of fish
      fillets harvested from the Great Lakes.

PMID- 7579932
TI  - Petroleum and chlorinated hydrocarbons in water from Lake Manzala and associated
      canals.

PMID- 7579934
TI  - Removal of chromium (III) from aqueous solution using chrome sludge.

PMID- 7579935
TI  - Residues of fluazifop-p-butyl following application to soybean.

PMID- 7579937
TI  - Identification of a point source of chlordane contamination from a timber
      treatment facility.

PMID- 7579936
TI  - Absorption, translocation, and accumulation of carbendazim in opium poppy
      (Papaver somniferum L.).

PMID- 7579938
TI  - Use of urinary p-nitrophenol as an index of exposure to parathion.

PMID- 7579940
TI  - Effect of p,p'-DDT and estrogen on the presence in the circulation and
      degranulation of blood eosinophil leukocytes.

PMID- 7579939
TI  - Dissipation of herbicide residues in the soil of a citrus orchard (Citrus
      sinensis L. Osbeck) after the ninth consecutive annual application.

PMID- 7579942
TI  - Respiratory effects and skin allergy in workers exposed to
      tetrachloroisophthalonitrile.

PMID- 7579941
TI  - Toxicity of 1,1-dichloroethane and 1,2-dichloroethylene determined using cultured
      human KB cells.

PMID- 7579943
TI  - [The clinical, laboratory and treatment aspects in streptoderma].

PMID- 7579945
TI  - [Pathogenic opportunistic microorganisms].

PMID- 7579946
TI  - [The epidemiology of cytomegalovirus infection].

PMID- 7579947
TI  - [Hepatitis B virus circulation in patients studied at the University Hospital of
      Bucharest].

PMID- 7579944
TI  - [3 cases of cutaneous mycosis: an analysis and the resulting conclusions].

PMID- 7579949
TI  - [Clinico-epidemiological observations on the relation between determining the
      cardiovascular risk--behavioral, constitutional and metabolic--and essential
      arterial hypertension].

PMID- 7579950
TI  - [The serological diagnosis of human leptospirosis].

PMID- 7579951
TI  - [The laboratory diagnosis of legionellosis].

PMID- 7579948
TI  - [An evaluation of a method for measuring apolipoproteins as a sensitive marker
      for estimating lipid metabolic disorder in a population at risk for essential
      arterial hypertension (EAH)].

PMID- 7579952
TI  - [Iuliu Moldovan as medical microbiologist].

PMID- 7579953
TI  - [Bacterial nutrition and respiration].

PMID- 7579954
TI  - Nosocomial propagation of multiresistant Staphylococcus aureus: an analysis using
      biotyping and drug sensitivity.
AB  - We performed an epidemiologic study of multi-resistant Staphylococcus aureus in
      our hospital. We combined bacteriologic biotyping and sensitivity to 19 drugs to
      conduct an environmental investigation. We assumed that complete matching in two
      or more strains denoted nosocomial propagation. A total of 667 isolates were
      recovered from a total of 144 patients. In a general surgical ward, 19 (52.8%)
      out of 36 patients developed an infection. The number of strains for every
      biotype and the combined susceptibility tended to show negative correlation (r = 
      0.376) before and after 1990, when an isolation policy was initiated. A similar
      regression analysis disclosed that between the general surgical ward and other
      wards the number of strains tended to show a positive association (r = 0.349).
      Thus, the isolation system employed in the general surgical ward may have
      arrested the persistence of intraward strains but permitted the interward travel
      of strains. In conclusion, an analysis of the propagation of multiresistant S.
      aureus using biotyping and drug sensitivity was found to be an effective method
      for evaluating the most appropriate measures to counter the endemic spread of
      this microbe.

PMID- 7579957
TI  - Preservation of the lower esophageal sphincter during total gastrectomy for
      gastric cancer to prevent postoperative reflux esophagitis.
AB  - The lower esophageal sphincter (LES) is usually removed during total gastrectomy
      to successfully perform a curative operation. In this study, the preservation of
      the LES in curative total gastrectomy was attempted to reduce the reflux. An
      experimental study using dogs has revealed that the high-pressure zone of the LES
      can be preserved by making a resection at the gastroesophageal junction, which
      thus helps to protect the reflux. A previous clinicopathological study revealed
      that the LES can be preserved without any fear of recurrence at the resection
      site, if the tumor is located more than 2.0 cm and 3.0 cm from the
      gastroesophageal junction to the oral margin in node-negative and -positive
      cases, respectively. Clinically, 8 patients underwent an LES-preserving total
      gastrectomy [LES(+) gastrectomy] while 19 had an LES(-) gastrectomy in the same
      period. Of the five LES(+) cases examined, all showed a high pressure zone,
      whereas none of the four LES(-) cases examined showed such a high-pressure zone
      after the operation. Endoscopic examination showed that only one of the seven
      LES(+) cases but six of nine LES(-) cases revealed esophagitis.

PMID- 7579958
TI  - Risk of gallstones following gastrectomy in Japanese men.
AB  - The risk of gallstones developing after gastrectomy in middle-aged Japanese men
      was investigated in a study of 2,738 men aged between 48 and 56 years who
      underwent both gallbladder ultrasonography (US) and a barium study of the upper
      digestive tract. It was revealed that 61 men had gallstones, 37 had had their
      gallbladder removed previously, and 55 had a history of gastrectomy. The
      prevalence of gallstones was 3.5 times higher in the men who had previously
      undergone gastrectomy (7.7%) than in those who had not (2.2%) (P = 0.03).
      Moreover, gallstones tended to be more prevalent in those who had undergone
      Billroth II gastrectomy (12.5%) compared with those who had undergone Billroth I
      gastrectomy (5.6%); however, the difference was not significant. These results
      indicate that gastrectomy using either Billroth I or Billroth II reconstruction
      predisposes to gallstone formation. Nevertheless, it was estimated that prior
      gastrectomy was responsible for no more than 5% of gallstones in the study
      population.

PMID- 7579956
TI  - Rapid turnover proteins as a prognostic indicator in cancer patients.
AB  - We investigated the relation between the plasma levels of various proteins,
      especially rapid turnover proteins (RTPs), and the prognosis in advanced cancer
      patients receiving total parenteral nutrition (TPN). In the patients with benign
      disease (n = 40), RTPs increased abruptly following TPN, but in patients with
      malignant disease, they rose slowly. Patients with malignant disease were divided
      into two different groups according to the outcome; group A, surviving 3 months
      or more after TPN and group B, who died within 3 months after TPN initiation.
      Whereas the RTP levels were elevated significantly in group A, they did not show
      any noticeable increase in group B. There was a close correlation between the
      plasma protein levels at 2 weeks and the survival time after TPN initiation.
      Thus, using the estimated critical values of RTPs with prognostic significance,
      the correct prognosis rate in 37 newly treated cases was: transferrin 75.7%,
      prealbumin: 91.9%, retinol-binding protein: 86.5%. These results clearly indicate
      that the TPN-induced changes in RTPs, notably in the PA value, can be a good
      prognostic indicator of survival in advanced cancer patients.

PMID- 7579955
TI  - Significance of the hepatic mitochondrial redox state in the development of
      posttraumatic jaundice.
AB  - The effect of the hepatic energy status on the development of posttraumatic
      jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients
      with severe torso injury who were expected to develop PTJ on admission with an
      average Injury Severity Score of 27 were selected for this study. They were
      retrospectively divided into three groups according to their maximum bilirubin
      concentration by day 10: group H, 12 patients with marked elevation of serum
      bilirubin (> 8 g/dl); group L, 23 with mild bilirubinemia (2-8 g/dl); and group
      N, 19 with no bilirubinemia (< 2 g/dl). Group H patients, in whom trauma-related
      shock was severe and prolonged, developed severe hyperbilirubinemia, and their
      arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox
      state and is closely correlated to its energy production, was significantly lower
      throughout the first week. In contrast, the AKBR increased to an above normal
      level, indicating enhanced energy production in groups N and L. The serum
      direct/total bilirubin was also higher in group H. The abnormal hepatic energy
      metabolism is considered to have reduced the excretion of conjugated bilirubin
      from the hepatocytes into the bile canaliculi, which is a process that has to
      proceed against the bilirubin concentration gradient. The subsequent diffusion of
      the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood
      is thus considered to be one of the causes of PTJ.

PMID- 7579959
TI  - Timing of surgery in relation to the menstrual cycle and its influence on the
      survival of Japanese women with operable breast cancer.
AB  - It has been suggested that the timing of surgery during periods of unopposed
      estrogen circulation, when high blood levels of estrogen and low blood levels of
      progesterone exist, has a deleterious effect on the survival of premenopausal
      patients with breast cancer. We studied this controversial issue by examining the
      serum estradiol and progesterone levels of 38 premenopausal patients with primary
      breast cancer, and by analyzing data on 100 premenopausal patients treated for
      primary breast cancer. The survival of 31 patients who had undergone initial
      surgery between days 3 and 12 after their last menstrual period (group E) was
      compared with that of 69 patients who had undergone surgery between days 0 and 2
      or from 13 days after their last menstrual period (group P). The overall survival
      of group E was significantly worse than that of group P (P = 0.049). This
      difference was especially notable in patients with node-positive tumors or tumors
      larger than 2 cm in size; however there was no significant difference in disease
      free survival between the two groups. On a multivariate analysis, nodal status
      was the only significant prognostic factor for both overall and disease-free
      survival. Thus, these findings suggest that unopposed estrogen circulation may be
      detrimental to the overall survival of premenopausal women with breast cancer.

PMID- 7579960
TI  - Surgical palliation of cardiac malformations associated with right isomerism.
AB  - Between 1985 and 1993, palliative surgery was performed on 13 pediatric patients
      who had complex cardiovascular anomalies associated with right isomerism. The
      patients included two neonates, ten infants, and one child who were divided into
      two groups according to whether or not a total anomalous pulmonary venous
      connection (TAPVC) was present. Group 1 consisted of six patients with TAPVC and
      group 2 consisted of seven patients without TAPVC. In group 1, the surgical
      procedures involved TAPVC repair alone in two patients, combined TAPVC repair
      with a modified Blalock-Taussig shunt in two, combined TAPVC repair with
      pulmonary artery banding in one, and a modified Blalock-Taussig shunt alone in
      one. There were five hospital deaths and one late death in this group: pulmonary
      venous obstruction in two patients, perioperative myocardial failure in the two
      neonates, and congestive heart failure caused by increased pulmonary blood flow
      in two patients. In group 2, all the patients underwent systemic-pulmonary artery
      shunts, and there was one hospital death and three late deaths, the causes of
      which were unknown in two patients, and shunt failure and pneumonia in one
      patient each. These results suggest that surgical palliation for right isomerism
      produces poor results in young infants with obstructed TAPVC. Thus, we conclude
      that TAPVC repair should be performed without delay if pulmonary venous
      obstruction has been diagnosed clinically. Resolving pulmonary venous obstruction
      without cardiopulmonary bypass (CPB) may be preferable for infants, considering
      their difficult management. The systemic-pulmonary artery shunt should be of the
      low-calibrated type, especially if common atrioventricular valve regurgitation
      exists. If infants survive the surgery, they must be carefully followed up for a
      long period due to the risk of sudden death or infection.

PMID- 7579961
TI  - Alterations in coagulation and fibrinolysis after surgery for aortic aneurysm.
AB  - We investigated the alterations in the coagulation and fibrinolysis systems after
      aortic aneurysm surgery under cardiopulmonary bypass (CPB) while using newly
      developed "molecular markers". Fibrinogen and antithrombin III (AT-III) decreased
      after surgery but returned to normal values within three days. The thrombin
      antithrombin III complex (TAT) and plasmin-alpha-2-plasmin inhibitor complex
      (PIC) both showed increased values even preoperatively, which indicated that
      coagulation and fibrinolysis were activated in some patients with an aortic
      aneurysm. Both markers maintained a high level for at least 14 days after
      surgery. The fibrin degradation product (FDP) also showed an increased value
      before and after surgery. These results apparently showed that
      coagulation/fibrinolysis had already been activated in some patients and
      maintained such a state for at least 14 days after surgery. The relation of
      activated system and postoperative organ dysfunction as well as the means to
      suppress such activation are also discussed.

PMID- 7579962
TI  - Alteration in the fluorescence polarization of rat plasma and liver cell
      membranes following bile duct ligation in rats.
AB  - The fluorescence polarization levels of liver cell membranes and plasma were
      analyzed to determine membrane fluidity following bile duct ligation (BDL) in
      rats. Fluorescence polarization was measured with a spectrofluorophotometer
      equipped with polarizers, using 1,6-diphenyl-1,3,5-hexatrien (DPH) as a probe.
      After bile duct ligation, liver cell membrane fluidity decreased significantly
      for up to 14 days after surgery (P < 0.001 on 3rd and 7th days). The polarization
      of the plasma in rats with BDL slightly but significantly increased compared to
      the levels in the control animals over the 14-day period following BDL. In
      addition, a small but significant correlation in the polarization levels between
      plasma and liver cell membranes (r = 0.362, P < 0.02) was observed. The co
      incubation of BDL plasma with normal liver cell membranes resulted in a decrease
      in membrane fluidity, which suggested that BDL rat plasma had a direct effect on
      membrane fluidity. After a 70% hepatectomy, the polarization of the membranes
      from remnant livers in the BDL rats remained elevated relative to the sham
      operated controls. It is thus concluded that the membrane fluidity of the livers
      in BDL rats decreases following bile duct ligation and does not increase after a
      70% hepatectomy, presumably due to the increased plasma level of bilirubin.

PMID- 7579963
TI  - Effects of glucose on rat lung preservation: report of a study conducted on an
      isolated lung reperfusion model utilizing. Another isolated lung as a
      "deoxygenator".
AB  - We describe herein a new experimental model in which an isolated rat lung was
      ventilated with a mixture of 95% nitrogen and 5% carbon dioxide to decrease the
      oxygen and increase the carbon dioxide in the perfused blood to create and
      maintain a gas composition similar to that of venous blood. By utilizing this
      system as a "deoxygenator," pulmonary functions, including gas exchange, could be
      measured for at least 60 min in isolated and preserved lungs on reperfusion. When
      the effects of glucose in the flushing and storage solution were examined, 5 mM
      glucose in the solution resulted in better preservation of the lung, as shown by
      a higher uptake of oxygen and a lower intratracheal pressure, than when no
      glucose was given. However, the presence of 50 mM glucose was not beneficial, but
      rather increased the wet/dry weight ratio of the tissue.

PMID- 7579964
TI  - Successful surgical treatment of secondary Kwashiorkor after total gastrectomy:
      report of a case.
AB  - We report herein the case of a 56-year-old woman who developed secondary
      Kwashiorkor 9 years after undergoing a total gastrectomy for early gastric
      cancer. Until she began developing the symptoms of Kwashiorkor, including general
      fatigue, edema of the face and extremities, anemia, alopecia, and weight loss,
      she had been leading a normal life post-gastrectomy. Her symptoms were alleviated
      by total parenteral nutrition (TPN) therapy, but reappeared soon after TPN
      therapy was discontinued. Therefore, she required several subsequent courses of
      TPN. In an attempt to permanently resolve the ongoing Kwashiorkor symptoms,
      reconstructive surgery involving transposition of the jejunum from the previous
      Graham method to the interposition method was performed 10 years after the
      initial gastrectomy. After the second operation, her malnutrition was completely
      alleviated, and she has been in good health for the 8 years since. To our
      knowledge, there has been no other report of the symptoms of secondary
      Kwashiorkor after total gastrectomy being alleviated by altering the procedure of
      reconstruction of the intestinal tract. Thus, we recommend surgical treatment to
      alter the digestive continuity to a more physiological pathway for selected
      patients with secondary Kwashiorkor syndrome.

PMID- 7579965
TI  - An intestinal fistula in a 3-year-old child caused by the ingestion of magnets:
      report of a case.
AB  - We describe herein the case of a 3-year-old child in whom a jejunoileal fistula
      was caused by the ingestion of magnets. This case report demonstrates that if
      more than one magnet is found as a foreign body in the intestine, they should not
      be left untreated even if there are no sharp edges and, it seems they could be
      evacuated spontaneously. This recommendation is made because the magnets will
      attract each other and hold the intestinal walls between them, causing necrosis
      and resulting in intestinal perforation or a fistula.

PMID- 7579966
TI  - Rupture of an isolated internal iliac artery aneurysm into the rectum: report of
      a case.
AB  - Aneurysmal rupture into the intestinal tract is a rare but disastrous
      complication of an internal iliac artery aneurysm. We report herein the
      successful surgical repair of a fistula between a huge aneurysm of the right
      internal iliac artery and the rectum in an 81-year-old man. After a femoro
      femoral cross-over bypass had been performed, the aneurysm was opened and its
      patent arterial branches were ligated with sutures. The fistula was then intra
      aneurysmally sutured and covered with an omental flap. The diagnostic and
      therapeutic approaches to this severe complication are discussed with a review of
      the literature following the presentation of this case.

PMID- 7579967
TI  - Successful management of portal hypertension following artificial arterioportal
      shunting: report of a case.
AB  - A 63-year-old woman diagnosed as having hepatic hilar cancer underwent an
      extended left lobectomy of the liver with excision of the right hepatic artery
      which was involved by the tumor. Because the hepatic artery could not be
      reconstructed by direct anastomosis, an artificial arterioportal (A-P) shunt was
      constructed between the common hepatic artery and the portal vein. However, 4
      weeks after the operation, portal hypertension with severe esophageal varices
      developed. Under the diagnosis of portal hypertension caused by excessive blood
      flow from the A-P shunt, coil embolization of the common hepatic artery was
      performed using an angiographic technique, following which the esophageal varices
      completely disappeared. This case demonstrates that portal hypertension after A-P
      shunting can be effectively treated with coil embolization.

PMID- 7579968
TI  - Successful surgical management of emphysematous giant bullae accompanied by
      severe bronchial asthma: report of a case.
AB  - The surgical treatment of emphysematous lung bullae is usually contraindicated in
      patients with severe bronchial asthma. However, we recently encountered a patient
      who required surgery due to the development of respiratory distress despite
      treatment with bronchodilators and low-dose prednisolone (5 mg/day). During the
      first operation, bronchospasm occurred with anesthesia. After suppression of the
      asthmatic symptoms for 2 weeks with high-dose prednisolone (25 mg/day), the giant
      bullae could be resected safely. Thus, the preoperative resolution of asthma to
      decrease the probability of an attack is indispensable for such patients.

PMID- 7579969
TI  - A new technique for performing mitral valve repair in a small left atrium.
AB  - A simple approach for exposing a difficult mitral valve within a small left
      atrium is described herein through the report of case. Mobilization of the
      superior vena cava with direct venous cannulation and extended dissection of the
      interatrial groove provide excellent mitral valve exposure, even in patients with
      a small left atrium.

PMID- 7579971
TI  - Catalytic antibodies: evolution of protein function in real time.
AB  - Natural selection of enzyme function has evolved over millions to billions of
      years, whereas antibody induction operates over a period of weeks. If one
      considers how new protein functions are generated, one sees that both the immune
      system and natural selection have powerful methods for the generation of
      diversity. In this treatise we discuss antibody catalysis from an evolutionary
      standpoint as we consider how the elicitation of a catalytic antibody can be a
      useful tool for exploring the nature of biological catalysis.

PMID- 7579970
TI  - Analysis of the structure of naturally processed peptides bound by class I and
      class II major histocompatibility complex molecules.
AB  - Antigen-specific T-cell responses require antigenic peptides presented on the
      cell surface by the major histocompatibility complex (MHC) molecules. The
      structural characteristics of these peptides are being defined. It is now known
      that the majority of peptides that associate with MHC Class I are 8-10 residues
      long, with allotype-specific binding motifs containing up to three anchor
      positions. This is consistent with the presence of six pockets and the close
      ended structure of the MHC Class I peptide binding groove. In contrast to
      peptides associated with MHC Class I, those associated with MHC Class II are 10
      34 residues in length and are commonly presented in nested sets with extensions
      or truncations at the N- or C-terminal ends. Binding motifs for MHC Class II
      appear to contain up to four anchor positions, with more loosely defined amino
      acid preferences. The expression of histocompatibility proteins in cells that do
      not load peptides but fold them correctly has permitted the X-ray analysis of the
      three-dimensional structure of Class I and Class II complexes with single defined
      peptides. The differences in length between the Class I and Class II sequences
      can be ascribed to small structural differences between the two binding sites and
      the positioning of key residues, that make hydrogen bonds to the bound peptides.
      Recent advances in mass spectrometry are making possible the analysis and
      sequencing of subpicomolar quantities of MHC-bound peptides and the estimation of
      the size of the total population of peptides. The sequence information derived
      from this technique, in conjunction with X-ray crystallographic analysis of MHC
      complexes involving single, defined peptides, may provide a new approach towards
      the development of useful reagents for therapeutic intervention.

PMID- 7579972
TI  - Chemical techniques employed for the primary structural analysis of proteins and
      peptides.
AB  - This chapter summarises modern microchemical approaches to the purification,
      identification and primary structure analysis of peptides and proteins.
      Discussion of high-sensitivity purification methods is restricted to two
      dimensional polyacrylamide gel electrophoresis (2-DE) and microbore/capillary
      column reversed-phase high-performance liquid chromatography (RP-HPLC).
      Associated techniques are discussed, particularly with respect to analysis of the
      products with current automated amino acid sequencers and mass spectrometers.

PMID- 7579973
TI  - UV and nucleic acids.

PMID- 7579975
TI  - Peptides as active probes.
AB  - The use of peptides as probes of peptide binding sites of neuropeptide receptors,
      and of peptidases and proteases is discussed. The rapidly expanding use of
      peptide antigens as probes of protein structure and valuable diagnostics and
      vaccines is described. We also discuss the use of synthetic peptide motifs in
      studies on the molecular details of protein-protein and protein-nucleic acid
      interactions. Covalently modified peptides such as phosphopeptides exemplifies
      the use of synthetic peptides in the study of posttranslational modifications of
      proteins.

PMID- 7579974
TI  - Chemical and enzymatic synthesis of glycopeptides.
AB  - Progress recently made in the synthesis of biologically relevant N- and O
      glycopeptides is illustrated by examples. In this context, developments in the
      preparation of complex saccharide side chains and in the subsequent coupling to
      peptide portions is described. Special emphasis is given to the synthesis of
      Lewis antigen-type structures. Furthermore, modern methods in solid phase peptide
      syntheses utilizing glycosylated building blocks are presented. Recent advances
      in glycopeptide syntheses employing enzymatic methods in deprotection steps as
      well as in peptide/saccharide chain elongation are reported.

PMID- 7579976
TI  - Zinc metallochemistry in biochemistry.
AB  - The chemically stable but stereochemically flexible, non-toxic nature of zinc
      combined with its amphoteric properties has permitted it to orchestrate a number
      of zinc-binding motifs critical to life processes. For zinc enzymes, catalytic,
      cocatalytic, and structural zinc sites exist. DNA-binding proteins have zinc
      fingers, twists, and clusters exist.

PMID- 7579977
TI  - NMR structural studies on the zinc finger domains of nuclear hormone receptors.
AB  - This chapter presents an overview of the application of modern NMR methods in
      structural studies of the DNA binding domains (DBDs) of nuclear hormone
      receptors. The DBDs studied so far comprise those of the glucocorticoid,
      estrogen, retinoic acid and retinoid X receptors. NMR spectroscopy has allowed
      the elucidation of the first structures of this family of C4-type zinc fingers,
      which led to a better understanding of their role in gene regulation.
      Crystallographic studies provided insight in protein-protein and protein-DNA
      interactions. Subsequent studies, applying NMR, have provided deeper insight into
      a diversity of issues concerning these proteins, ranging from backbone dynamics
      and metal coordination to the interaction of these domains with their DNA target
      sites. From this work a picture emerges of a class of closely related zinc
      binding proteins which, despite their strong sequence homology, exhibit
      interesting structural and functional differences between members of different
      subfamilies.

PMID- 7579979
TI  - Protein sorting signals: simple peptides with complex functions.
AB  - Protein sorting signals provide good examples of peptides that can be studied
      both from a chemical and a biochemical perspective. Their simple designs and low
      degree of sequence conservation suggest that they are involved in rather non
      specific peptide-lipid interactions, yet their ability to discriminate
      efficiently between the import machineries of different subcellular compartments
      rather points to the importance of peptide-receptor interactions. The study of
      protein sorting signals thus invites a cross-disciplinary approach.

PMID- 7579978
TI  - Lipase structures at the interface between chemistry and biochemistry.
AB  - In this chapter we review recent molecular knowledge on two structurally related
      mammalian triglyceride lipases which have evolved from a common ancestral gene.
      The common property of the lipase family members is that they interact with non
      polar substances. Pancreatic lipase hydrolyzes triglycerides in the small
      intestine in the presence of many dietary components, other digestive enzymes and
      high concentrations of detergents (bile salts). Lipoprotein lipase acts at the
      vascular side of the blood vessels where it hydrolyses triglycerides and some
      phospholipids of the circulating plasma lipoproteins. A third member of the gene
      family, hepatic lipase, is found in the liver of mammals. Also, this lipase is
      involved in lipoprotein metabolism. The three lipases are distantly related to
      some non-catalytic yolk proteins from Drosophila (Persson et al., 1989;
      Kirchgessner et al., 1989; Hide et al., 1992) and to a phospholipase A1 from
      hornet venom (Soldatova et al., 1993).

PMID- 7579980
TI  - Enzymes: chemistry and biochemistry.
AB  - Basic principles underlying enzyme action are considered. Catalytic antibodies
      (abzymes), catalytic RNA (ribozymes), and non-biological counterparts of enzyme
      catalyzed reactions are mentioned. Enzyme evolution is considered in terms of
      divergence, convergence, and lateral gene transfer.

PMID- 7579981
TI  - AHNA certification program in holistic nursing courses; AHNA certificate program
      in healing touch courses.

PMID- 7579982
TI  - AHNA-AHMA 1995 Joint Conference: a sacred moment in time.

PMID- 7579984
TI  - The use of anti-psychotic drugs with adults with learning disabilities and
      challenging behaviour.
AB  - The use of anti-psychotic medication with an adult population of people with
      learning disabilities and challenging behaviours was investigated as part of an
      epidemiological study covering seven district health authorities and
      corresponding local authorities in North West England. The study found a high
      rate of prescription of anti-psychotic drugs (48.1%). Chlorpromazine was the most
      frequently prescribed drug, followed by Thioridazine and Haloperidol. Three
      variables, psychiatric diagnosis, where the person was resident (hospital
      disturbed ward, hospital non-disturbed ward, hostel or family home) and district
      of origin were found to be significant determinants of prescriptions when all
      other variables were controlled. Of the variables reflecting individual
      characteristics those significantly related to prescription suggested that the
      socially disruptive effects of challenging behaviour were determining
      prescription. The results are discussed in the context of differing prescription
      practices across residence and district in the context of the management of
      socially disruptive behaviour.

PMID- 7579985
TI  - The dexamethasone suppression test and the diagnosis of depression in adults with
      severe and profound developmental disabilities.
AB  - The dexamethasone suppression test (DST) was administered to 40 adults with
      severe and profound mental retardation. All participants were free from known
      conditions which may have given misleading results from cortisol assay. Of nine
      participants who showed symptoms possibly indicating depression the DST results
      concurred in two cases (i.e. there were two true-positives). However there were
      four or five (depending on criteria adopted) false-positive DST results. There
      did not appear to be a consistent behavioural profile for positive DST
      responders. With sensitivity to possible depression estimated at 22%, and a
      diagnostic confidence of < 35%, these data do not support recommendations that
      the DST is useful for assisting in diagnosis of depression in this population.

PMID- 7579983
TI  - Measurement of attitudes of trainee professionals to people with disabilities.
AB  - The importance of measuring attitudes of trainee professionals to people with
      disabilities was addressed. A questionnaire which included the Scale of Attitudes
      toward Disabled Persons (SADP) and the Intellectual Disability Misconceptions
      Scale (IDMS) was completed by first and final year tertiary students enrolled in
      a 3-year course on intellectual disability. The attitude measures did not
      discriminate between the two groups of students, psychometric properties were
      poor and the factor structure of the SADP did not replicate previous findings. As
      expected, there was some convergence between the two attitude measures, and
      relationships to subject variables were consistent with previous research.
      Recommendations for subsequent research were discussed.

PMID- 7579986
TI  - Personality and trait disturbances in an adult mental retardation population:
      significance for psychiatric management.
AB  - The authors demonstrate the high prevalence of personality disorders in 384
      intellectually impaired individuals examined in both community and institutional
      settings in southwestern Ontario, Canada. The relationship of specific clusters
      of personality disorders to later onset of psychiatric disorders in
      intellectually impaired individuals is suggested. New approaches to the
      management of personality disorders are noted utilizing clinical case studies.
      Differences and similarities in nomenclature in American and International
      diagnostic classifications are illustrated in this study. The use of a detailed
      longitudinal and cross-sectional collection of biological, social and
      standardized personality schedules is demonstrated as feasible in this special
      population.

PMID- 7579987
TI  - Attachment and learning disability: a theoretical review informing three clinical
      interventions.
AB  - Attachment theory makes sense of two phenomena observed in some people with
      learning disabilities: it provides a reason for their limited exploration of the
      world, and it explains discontinuities in the pattern and intensity of their
      expressions of anger. Applying this framework to three enmeshed relationships
      occurring between an adult with learning disabilities and a member of care staff
      achieved at least partial resolution of their problems. Attachment theory's
      critics have set a number of challenges for its proponents, including emphasizing
      an interactional rather than a unidirectional approach to relationships;
      prioritizing social context; and understanding the attachment dynamic
      dimensionally rather than as a set of categories. The latter issue is pertinent
      for residential services: facilitating secure attachment relationships for
      distressed clients may be difficult for professionals, but partial assuagement of
      their attachment needs is a realistic clinical goal.

PMID- 7579990
TI  - Fragile-X and Down's syndrome: are there syndrome-specific cognitive profiles at
      low IQ levels?
AB  - Individuals with either fragile-X syndrome or Down's syndrome with IQ scores less
      than 40 were assessed on the Down Syndrome Mental Status Exam. The results of the
      testing were examined for syndrome-specific cognitive profiles. No evidence for
      syndrome-specific cognitive profiles were found. These same individuals were then
      classified as high or low IQ, and each group was examined for IQ-level-specific
      profiles. Unique IQ level cognitive profiles were found. Classifying the
      individuals with regard to aetiology obscured IQ-level-specific strengths and
      weaknesses. Researchers and developers of curricula are cautioned against
      generalizing cognitive profiles to all IQ levels of a specific genetic syndrome.

PMID- 7579989
TI  - Influence of mental retardation severity and respondent characteristics on self
      reported attitudes toward mental retardation and eugenics.
AB  - Eugenics refers to the investigation of means of social control to improve the
      mental or physical qualities of future generations. The present study
      investigated whether the self-reported attitudes toward mental retardation and
      eugenics of a sample of 572 respondents would vary as a function of (I) severity
      of the mental retardation attitude referent; and (2) respondent sociodemographic
      characteristics. Among the respondents, 380 were health and human service
      providers (66% upper division undergraduate students and 34% graduate level
      professionals) and 192 were upper division undergraduate students majoring in
      fields other than health and human services. The results supported these
      conclusions: (1) psychometric characteristics of the scales used to measure
      attitudes were adequate; (2) increasing mental retardation severity was related
      to increasing endorsement of eugenic principles, independent of global attitudes
      toward people with mental retardation; and (3) respondent education was related
      to the expression of eugenic attitudes toward mild mental retardation, while
      familiarity with people with mental retardation was related to the expression of
      eugenic attitudes toward moderate and profound mental retardation.

PMID- 7579988
TI  - Care dependence and individual care provision.
AB  - For policy purposes as well as for the provision of individual care, it is
      relevant to known which individual characteristics have impact upon the level of
      care dependence. For purposes of individual care provision, characteristics which
      can be influenced and which also have an important impact upon the care
      dependence are of interest. This study showed that the profoundly mentally
      handicapped are almost all totally dependent upon care, and therefore additional
      information about individual characteristics is superfluous. The results of
      logistic regression analyses showed a statistically significant and important
      impact of ADL-functions. Exactly which other characteristics are relevant to
      consider depends upon the level of care dependence and the level of mental
      handicap.

PMID- 7579991
TI  - Response biases in interviews of individuals with limited mental ability.
AB  - The validity of responses by individuals with mental retardation during
      interviews is threatened by a number of biases. Acquiescence (the disposition to
      answer 'yes' regardless of the question asked) is a commonly observed response
      bias committed by respondents to questionnaires and interviews, and this
      disposition is significantly more pronounced when persons of low status are
      questioned by high-status interviewers. Research on the acquiescence bias
      suggests that it can be reduced in mentally retarded respondents by replacing the
      usual 'yes/no' question format with an 'either/or' format. Enhancing the
      either/or choices with accompanying picture representations of each choice is
      beneficial in increasing mentally retarded subjects' responding and in reducing
      their tendency to choose the latter of two either/or choices. 'Nay-saying' (the
      disposition to say 'no' regardless of the question asked), while less common than
      'yea-saying' (i.e. than acquiescence), has also been noted in response to certain
      question formats and taboo topics. This review implies that the validity of an
      interview with respondents of limited intelligence depends greatly on the format
      of its questions.

PMID- 7579992
TI  - Beliefs and emotional reactions of care staff working with people with
      challenging behaviour.
AB  - Information collected in the context of a survey of all people with learning
      disabilities and challenging behaviour in a single metropolitan borough
      indicated: (1) care staff report that a significant proportion of their
      colleagues usually display such emotional reactions as sadness, despair, anger,
      annoyance, fear and disgust to episodes of challenging behaviour; (2) respondents
      reported that the most significant sources of stress associated with caring for
      someone with challenging behaviour centred upon the 'daily grind' of caring,
      their difficulty in understanding the person's behaviour, the unpredictability of
      the behaviour and the apparent absence of an effective way forward; (3) care
      staff attribute the causes of the person's challenging behaviour to a diversity
      of internal psychological, broad environmental, behavioural and medical factors.
      These results are discussed in relation to their implications for staff-seeking
      and implementing external advice regarding the management of challenging
      behaviour.

PMID- 7579993
TI  - The Behavior Problem Inventory: a further replication of its factor structure.
AB  - The Behavior Problem Inventory was administered to a random sample of people
      living in a state school. The scores from all items and from self-injury items
      only were factor analysed. The three scales of the Behavior Problem Inventory
      were highly internally consistent. Factor analysis of all the items showed some
      similarities to previous studies, and factor analysis of the self-injury items
      showed a very close correspondence to two previous studies. The results are
      discussed in terms of the design of this instrument, the possible multi-factorial
      nature of self-injury and future research on the design of measures of
      assessments of maladaptive behaviours in people with developmental disabilities.

PMID- 7579994
TI  - Dehalogenation of 4-chlorobenzoate. Characterisation of 4-chlorobenzoyl-coenzyme
      A dehalogenase from Pseudomonas sp. CBS3.
AB  - Pseudomonas sp. CBS3 is capable of growing with 4-chlorobenzoate as sole source
      of carbon and energy. The removal of the chlorine of 4-chlorobenzoate is
      performed in the first degradation step by an enzyme system consisting of three
      proteins. A 4-halobenzoate-coenzyme A ligase activates 4-chlorobenzoate in a
      coenzyme A, ATP and Mg2+ dependent reaction to 4-chlorobenzoyl-coenzyme A. This
      thioester intermediate is dehalogenated by the 4-chlorobenzoyl-coenzyme A
      dehalogenase. Finally coenzyme A is split off by a 4-hydroxybenzoyl-CoA
      thioesterase to form 4-hydroxybenzoate. The involved 4-chlorobenzoyl-coenzyme A
      dehalogenase was purified to apparent homogeneity by a five-step purification
      procedure. The native enzyme had an apparent molecular mass of 120,000 and was
      composed of four identical polypeptide subunits of 31 kDa. The enzyme displayed
      an isoelectric point of 6.7. The maximal initial rate of catalysis was achieved
      at pH 10 at 60 degrees C. The apparent Km value for 4-chlorobenzoyl-coenzyme A
      was 2.4-2.7 microM. Vmax was 1.1 x 10(-7) M sec-1 (2.2 mumol min-1 mg-1 of
      protein). The NH2-terminal amino acid sequence was determined. All 4-halobenzoyl
      coenzyme A thioesters, except 4-fluorobenzoyl-coenzyme A, were dehalogenated by
      the 4-chlorobenzoyl-CoA dehalogenase.

PMID- 7579995
TI  - Use of haloacetate dehalogenase genes as selection markers for Escherichia coli
      and Pseudomonas vectors.
AB  - The haloacetate dehalogenase gene, dehH2, cloned from Moraxella sp. strain B
      could be used a selection marker gene for vectors in Escherichia coli and
      Pseudomonas putida. Haloacetates, especially iodoacetate, inhibit the growth of
      some microorganisms. The dehH2 gene introduced into the cells conferred
      iodoacetate resistance on them. Therefore, E. coli and P. putida transformed with
      vectors marked with dehH2 could be easily selected on plates containing
      iodoacetate.

PMID- 7579996
TI  - Cloning and expression of a haloacid dehalogenase from Pseudomonas sp. strain 19
      S.
AB  - A dehalogenase gene specifying the utilization of a variety of haloacids by
      Pseudomonas sp. Strain 19S has been cloned and expressed in E. coli. Our cloning
      strategy employed specific amplification of a fragment homologous to Pseudomonas
      dehalogenase gene by Polymerase Chain Reaction (PCR). The PCR amplicon
      successfully acted as a probe to detect the dehalogenase gene in the Southern
      Blot of the digested Pseudomonas total DNA. Corresponding fragments were cloned
      into pUC 18 vector and amplified in E. coli MV 1190. One clone with a substantial
      dehalogenation activity carried a recombinant plasmid containing a 5.5 kb insert.

PMID- 7579997
TI  - Overexpression and feasible purification of thermostable L-2-halo acid
      dehalogenase of Pseudomonas sp. YL.
AB  - The gene encoding thermostable L-2-halo acid dehalogenase of Pseudomonas sp. YL
      was isolated, and its overexpression system was constructed. Gene library was
      prepared from Sau3AI fragments of total DNA from Ps. sp. YL, pUC118 as a vector
      and Escherichia coli JM109 as a host. The recombinant cells resistant to
      bromoacetate, a germicide, were isolated and shown to produce L-2-halo acid
      dehalogenase. Subsequently, subcloning was carried out with pKK223-3 as a vector,
      and the length of DNA inserted was reduced to 1.1 kbp. One of the subclones
      showed very high activity, and the amount of the dehalogenase produced
      corresponded to about 30% of the soluble protein. From 5 g (wet weight) of cells,
      105 mg of dehalogenase was efficiently purified by heat treatment and DEAE
      Toyopearl chromatography. This overexpression system provides a large amount of
      the thermostable enzyme to enable us to study the properties, structure and
      application of the enzyme.

PMID- 7579998
TI  - Dehalogenation of haloalkanes by Rhodococcus erythropolis Y2. The presence of an
      oxygenase-type dehalogenase activity complements that of an halidohydrolase
      activity.
AB  - Rhodococcus erythropolis Y2 produced two types of dehalogenase: a hydrolytic
      enzyme, that is an halidohydrolase, which was induced by C3 to C6 1-haloalkane
      substrates, and at least one oxygenase-type dehalogenase induced by C7 to C16 1
      haloalkanes and n-alkanes. The oxygenase-type activity dehalogenated C4 to C18 1
      chloroalkanes with an optimum activity towards 1-chlorotetradecane. The
      halidohydrolase catalysed the dehalogenation of a wide range of 1- and
      alpha,omega-disubstituted haloalkanes and alpha,omega-substituted haloalcohols.
      In resting cell suspensions of hexadecane-grown R. erythropolis Y2 the oxygenase
      type dehalogenase had a specific activity of 12.9 mU (mg protein)-1 towards 1
      chlorotetradecane (3.67 mU mg-1 towards 1-chlorobutane) whereas the
      halidohydrolase in 1-chlorobutane-grown batch cultures had a specific activity of
      44 mU (mg protein)-1 towards 1-chlorobutane. The significance of the two
      dehalogenase systems in a single bacterial strain is discussed in terms of their
      contribution to the overall catabolic potential of the organism.

PMID- 7579999
TI  - The nucleotide sequence of a transposable haloalkanoic acid dehalogenase
      regulatory gene (dehRI) from Pseudomonas putida strain PP3 and its relationship
      with sigma 54-dependent activators.
AB  - The mobile genetic element, DEH found in Pseudomonas putida PP3 carries a 2
      haloalkanoic acid dehalogenase structural gene, dehI, and its associated
      regulatory gene, dehRI. The nucleotide sequence of dehRI was determined. The gene
      had an open reading frame putatively encoding for a 64 kDa protein containing 571
      amino acid residues. The protein was similar to previously published sequences of
      several other sigma 54-dependent activator proteins. Amino acid sequence analysis
      showed that the deduced DehRI protein clustered with the NifA nitrogenase
      regulatory activator family, and was most closely related, with 47.7% similarity,
      to a 'NifA-like' deduced partial sequence from a plasmid-encoded ORF in
      Pseudomonas sp. strain NS671, associated with L-amino acid production. The domain
      structure of DehRI was analysed by alignment with other NifA-like and NtrC-like
      sequences and showed a highly conserved central region of approximately 230 amino
      acids, and a potential DNA-binding domain. No homology was detected between the
      deduced DehRI and other sigma 54-dependent activator sequences at the N-terminus,
      a result which was consistent with that region being the domain which recognised
      inducer.

PMID- 7580001
TI  - Special issue: selected papers from the 50th Annual Meeting of the American
      Fertility Society. San Antonio, Texas, November 5-10, 1994.

PMID- 7580000
TI  - Sequence analysis of the upstream region of dhlB, the gene encoding haloalkanoic
      acid dehalogenase of Xanthobacter autotrophicus GJ10.
AB  - The DNA sequence upstream of the dhlB gene encoding the haloalkanoic acid
      dehalogenase of Xanthobacter autotrophicus GJ10 was determined and contained an
      open reading frame, designated dhlC, which encoded a protein with a significant
      similarity with the family of Na(+)-dependent symport proteins. The dhlC gene was
      subcloned under control of a T7 promoter, and found to encode a polypeptide of 45
      kDa on SDS-PAGE. Upstream of dhlC, a -24/-12 promoter sequence was found. Further
      upstream, in the opposite direction of transcription, another open reading frame,
      designated dhlR, with homology with the family of sigma 54-dependent
      transcriptional activator proteins was detected. The dhlR gene was cloned and
      expressed under the control of a T7 promoter and encoded a polypeptide of 51 kDa
      on SDS-PAGE. The genetic organization of the dhlB region suggested that the
      expression of dhlC and dhlB was controlled by the product of dhlR and sigma 54
      which may explain the observed overexpression of the haloalkanoic acid
      dehalogenase under starvation conditions.

PMID- 7580002
TI  - Predictive value of hCG level 14 days after embryo transfer.
AB  - OBJECTIVE: It has been reported that the quantitative serum hCG level 14 days
      after embryo transfer (ET) correlated with pregnancy outcome as well as a
      likelihood of a multiple gestation pregnancy. This prospective study was designed
      to assess the predictive value of a 14-day post-ET hCG level with pregnancy
      outcome and multiple gestation pregnancies. METHODS: Patients undergoing in vitro
      fertilization (IVF) and ET were monitored by serum quantitative hCG levels 14
      days after ET. If positive, serial values of hCG were obtained and transvaginal
      ultrasound was performed 3 weeks after ET and weekly until fetal cardiac activity
      was seen. Ongoing pregnancies were defined as greater than 20 weeks. RESULTS: One
      hundred eleven patients had positive serum quantitative hCG levels 14 days post
      ET; 89/111, or 80.2%, had ongoing pregnancies. The spontaneous miscarriage rate
      was, therefore, 19.8% (22/111). If the level was less than 300, the ongoing
      multiple pregnancy rate was 9% (5/57). If the level was between 300 and 600, the
      ongoing pregnancy rate was 40% (10/25). If the hCG level was greater than 600,
      the multiple pregnancy rate was 100% (7/7). CONCLUSIONS: These data support the
      hypothesis that hCG levels greater than 200 mIU/ml on 14 days post-ET are more
      likely to have ongoing pregnancies; hCG levels greater than 600 have a high
      likelihood of a multiple gestation pregnancy.

PMID- 7580003
TI  - Comparison between depot leuprorelin and daily buserelin in IVF.
AB  - OBJECTIVES: To compare the effects of depot and daily forms of GnRH analogs in
      IVF programs. METHODS: One hundred seventeen patients undergoing IVF, with no
      severe male factor, were randomized between two treatment groups. Pituitary
      desensitization was obtained in group 1 (60 patients) with a single IM injection
      of leuprorelin (3.75 mg), and in group 2 (57 patients) with buserelin (0.3 mg SC
      twice daily). In a subgroup of 10 patients (5 for the depot form and 5 for the
      daily form) several GnRH tests were performed to investigate pituitary
      desensitization. RESULTS: No differences were found in the time to reach
      desensitization. Resumption of pituitary activity occurred in 7 days with the
      daily form and in about 2 months with the depot form. No significant differences
      were found in the stimulation pattern, oocyte quality, percentage of
      fertilization. The pregnancy rate per transfer was slightly, but not
      significantly, better in the depot group (29.4% vs 25.9%). Implantation rate
      (11.9% vs 12.3%) and the percentage of miscarriages (26.6% vs 28.5%) were
      similar. CONCLUSION: Depot and daily forms of GnRH analogs are equally effective
      in superovulation induction for IVF. Considering improved patient compliance and
      preference, depot forms are advantageous.

PMID- 7580005
TI  - Screening of maternal sera using a mouse embryo culture assay is not predictive
      of human embryo development or IVF outcome.
AB  - PURPOSE: Maternal serum is commonly added to media used for human IVF but can
      vary widely in its ability to support the development of human embryos in vitro.
      The objective of this study was to determine if the screening of maternal serum
      with a mouse one-cell embryo culture assay would be useful in predicting human
      embryo development and clinical outcome following IVF. METHODS: Twenty-two
      individual serum samples from IVF patients were used as a supplement (7.5%) to
      Ham's F-10 media for culturing human embryos. All embryos were evaluated at the
      time of transfer for stage of development and embryo quality. Each serum sample
      was also tested for its ability to support mouse embryo development. One-cell
      embryos were recovered from superovulated female mice and cultured in serum
      supplemented media. Mouse blastocyst development was assessed after 96 h of
      incubation. RESULTS: No correlation was found between mouse blastocyst formation
      and human embryo development in media supplemented with maternal sera. Similarly,
      there was no association between the development of mouse blastocysts and
      clinical outcome following IVF. A subanalysis of patients whose sera tested
      poorly on the mouse assay again revealed no association between mouse and human
      embryo development. CONCLUSION: Mouse embryo development in media containing
      human serum did not predict development of human embryos in vitro or clinical
      outcome following IVF. There would be little benefit to screening maternal sera
      using a mouse embryo culture system for determining its suitability for use in
      human IVF.

PMID- 7580007
TI  - Familial endometriosis.
AB  - PURPOSE: The study aimed to identify families with endometriosis and to document
      disease severity within the families and the clinical characteristics of the
      affected women. RESULTS: Two hundred and thirty women with surgically confirmed
      endometriosis in 100 families were identified. The families consisted of 19
      mother-daughter pairs, 1 set of cousins and 56 sister pairs. There were 5
      families with 3 affected sisters, 1 family with 5 affected sisters, and 18
      families with > or = 3 affected members in more than one generation. The mean age
      at the onset of symptoms and the mean age at surgical diagnosis was 22.1 +/- 8.8
      SD (range 10-46) and 31.8 +/- 7.9 SD (range 15-56) years respectively. Seventy
      nine women (34.3%) had revised AFS Stage I-II disease, and 151 (65.7%) had
      revised AFS Stage III-IV disease. CONCLUSION: The study confirms a familial
      tendency for endometriosis and supports the hypothesis that endometriosis has a
      genetic basis.

PMID- 7580004
TI  - Enzymatic characterization of zona pellucida hardening in human eggs and embryos.
AB  - PURPOSE: To characterize possible hardening of the human zona pellucida (ZP) and
      evaluate the effect of culture duration, patient age, and ZP thickness, ZP of
      unfertilized eggs (experiment 1, n = 367; experiment 2, n = 174) and abnormal
      embryos (experiment 1, n = 52) were randomly designated for alpha-chymotrypsin
      treatment after 0, 24, 48, 72, 96, 120 h (experiment 1) and 48 h, 72 h, and 1
      week (experiment 2) of in vitro culture in HTF medium supplemented with 0.5%
      human serum albumin. Mean ZP thickness was predetermined in experiment 2.
      METHODS: The dispersion of the ZP glycoproteins was assessed, and the duration of
      time for complete digestion was recorded as an index of ZP hardness. RESULTS: In
      experiment 1, enzyme digestion duration increased (P < 0.05) in the first 24 h in
      vitro from 18.0 +/- 2.0 to 34.6 +/- 2.5 min, and tended to decrease over the next
      4 days in culture (25.2 +/- 1.3, 29.4 +/- 0.9, 27.3 +/- 0.6, 26.6 +/- 1.1, and
      20.7 +/- 1.5 min on Day 2-6 ZP, respectively). Zona hardening of fertilized eggs
      was revealed by a longer (P < 0.01) digestion time (32.2 +/- 1.8 vs 25.8 +/- 0.6
      min). CONCLUSIONS: There were significant patient-to-patient variation (16.4 +/-
      0.7 to 39.6 +/- 2.2 min); however, age was not correlated to enzyme digestion
      duration. In experiment 2 we determined that ZP thickness (range 8.4-21.6
      microns; mean 14.6 +/- 0.2 microns) was not correlated (r = 0.09) to the
      digestion interval (mean 24.3 +/- 0.8 min). Based on our enzymatic ZP digestion
      measurements, it is apparent that spontaneous zona hardening does occur within 24
      h of in vitro culture, similar to levels achieved postfertilization. The data do
      not support, however, the concept that additional, abnormal hardening of the ZP
      occurs during extended culturing.

PMID- 7580006
TI  - Superovulation before IVF by recombinant versus urinary human FSH (combined with
      a long GnRH analog protocol): a comparative study.
AB  - PURPOSE: Gonal-F (Serono, Aubonne, Switzerland) is a recombinant human follicle
      stimulating hormone (FSH) synthesized in vitro by cells into which genes encoding
      for FSH subunits have been inserted. This preparation exhibits physiochemical,
      immunological, and pharmacological properties that bear great similarity to those
      of native human FSH. It has a high specific activity and can be administered
      subcutaneously. To compare the efficacy and safety of Gonal-F with those of
      urinary human FSH (Metrodin; Serono) in achieving superovulation for IVF purposes
      in a prospective, randomized study. METHODS: Twenty infertile patients (normo
      ovulatory healthy women) were recruited for the study and allocated at random to
      the Gonal-F or Metrodin groups. The treatment protocol consisted of pituitary
      down regulation by GnRH analog (Buserelin; Hoechst, Frankfurt, Germany) employing
      the "long" protocol initiated at the mid-luteal phase (900 micrograms/day,
      intranasal administration). Gonal-F (SC) or Metrodin (IM) was injected daily (225
      IU/day) starting on cycle day 3. Dose adjustment was performed, when necessary,
      from cycle day 7. RESULTS: Of the 20 cycles analyzed, none was canceled due to
      poor response. No cases of adverse effects (including local intolerance) or
      ovarian hyperstimulation syndrome were recorded in either group. They did not
      differ significantly in the following treatment-dependent variables: hormone
      profile, duration of FSH treatment, total FSH dose required to achieve follicular
      maturation, and the number of oocytes retrieved, fertilized, and replaced.
      CONCLUSIONS: These preliminary data concur with previous studies in demonstrating
      that Gonal-F is as effective and safe as Metrodin (when given in combination with
      a "long" protocol of GnRH analog) in inducing controlled ovarian hyperstimulation
      for IVF purposes. Its mode of administration (SC instead of IM) offers an
      additional advantage over the urinary human FSH.

PMID- 7580008
TI  - Cytogenetic and cryobiology of human cocultured embryos: a 3-year experience.
AB  - PURPOSE: Coculture, which allows good-quality human blastocysts with good yields
      to be obtained, has been designed mainly to select the best embryos for
      transfers. METHODS: In a first attempt during coculture, we have studied by
      fluorescent in situ hybridization the chromosomic content of the in vitro blocked
      embryos, using centrometric probes for chromosomes 1, 12, and 18. Close to 37% of
      the arrested embryos show aneuploidymosaicism. RESULTS: Freezing cocultured
      blastocysts gives good recovery rates after transfer (83%). The ongoing pregnancy
      rates per transfer (19%) are high, and the implantation rate per embryo is 13%.
      This compares favorably with freezing at an early stage. CONCLUSIONS: We observed
      that the quality of the endometrium is always the limiting step, as first of all
      we observed wide variations according to the hormonal preparation of the
      patients. Moreover the implantation per embryo in the pregnant patients is very
      high (57%), indicating that most of the losses are directly related to the
      receptivity of the endometrium.

PMID- 7580009
TI  - Effects of hydrogen peroxide on human spermatozoa.
AB  - PURPOSE: Reactive oxygen species (ROS) have been reported widely to cause
      deleterious effects on sperm viability and function due to peroxidation of
      membrane lipids. However, their action appears more selective at low
      concentrations; recent evidence indicates that the superoxide anion can promote
      capacitation and induce hyperactivated motility (HA) in human spermatozoa and
      that hydrogen peroxide (H2O2) may participate in capacitation of hamster
      spermatozoa. The objective of these studies was to investigate the direct effects
      of H2O2 on functions crucial to fertilization in human spermatozoa. METHODS: In
      these prospective studies, we examined the dose- and time-dependent effects of
      H2O2 on sperm membrane-mediated events (binding to the zona pellucida and changes
      in intracellular calcium concentration [Ca2+]i, motility patterns, and acrosome
      reaction). Sperm from fertile donors were used in the experiments under
      capacitating conditions after separation of the motile fraction by wash/swim-up.
      [Ca2+]i was measured by the fluorescent fura-2 indicator, and sperm-zona
      pellucida binding was assessed with the hemizona assay (HZA). Hyperactivated
      motility was evaluated by computerized analysis, and the percentage of acrosome
      reacted sperm was detected by FITC-Pisum sativum lectin and indirect
      immunofluorescence. RESULTS: In the HZA, H2O2 did not influence sperm-zona
      pellucida binding at low concentrations (0.05 mM and 0.1 mM), but significantly
      reduced binding at 0.2 mM (P < 0.004 vs controls). H2O2 significantly decreased
      HA in a dose-dependent manner (P < 0.0001) and had a significant effect (P <
      0.01) on acrosome reaction (stimulatory effect at 0.01 mM). H2O2 did not affect
      basal [Ca2+]i; however, H2O2 (0.1 mM through 10 mM) decreased the initial phase
      of progesterone-induced (P4: 1 microM) enhancement of [Ca2+]i in a dose- and time
      dependent fashion. Preincubation of sperm with catalase (20 micrograms/ml)
      potentiated the P4-induced increase of [Ca2+]i. H2O2 did not significantly modify
      [Ca2+]i increase in response to inomycin (10 microM). CONCLUSIONS: These
      experiments show that H2O2 directly affects sperm functions crucial to
      fertilization in a dose- and time-dependent fashion. Low concentrations maintain
      capacitation, whereas higher concentrations have deleterious effects, as
      determined by the end points of the capacitation process. The latter effects are
      probably dependent on modifications of plasma membrane and intracellular
      homeostasis by the oxidative process.

PMID- 7580010
TI  - Effect of Percoll wash on sperm motion parameters and subsequent fertility in
      intrauterine insemination cycles.
AB  - PURPOSE: This study examined sperm motion parameters as measured by computerized
      automated semen analysis before and after a Percoll wash and determined if
      differences in any parameter were correlated with fertility subsequent to
      intrauterine insemination (IUI). RESULTS: Total motile sperm decreased following
      the washing procedure from 79.0 +/- 9.0 to 37.2 +/- 7.6 million sperm. Motility
      increased from a mean of 43.4% to 61.7% (P < 0.001). Other motility parameters
      also changed significantly (P < 0.001) as follows: curvilinear velocity (VCL),
      43.4 to 61.7 microns/s; straight-line velocity (VSL), 21.3 to 26.7 microns/s;
      linearity 53.1 to 45.2%; lateral head displacement (ALH), 2.97 to 3.94 microns.
      Similar changes occurred following a swim-up preparation, although changes in
      mean motility, VCL, and ALH were significantly greater when compared to Percoll.
      The postwash changes were not accounted for merely by time lapse in preparation
      since reanalyzed untreated controls did not show the same changes in motion
      parameters. Prewash linearity in those specimens which resulted in pregnancies
      was greater than in those which did not (P = 0.28). No other significant
      differences in pre- or post-Percoll washed sperm motion parameters were found
      between pregnant vs nonfertile cycles. CONCLUSION: Following Percoll wash all
      CASA-generated motility parameters were significantly altered, but there was
      little association between these parameters and pregnancy achieved in IUI cycles.

PMID- 7580012
TI  - Recombinant-human luteinizing hormone (r-hLH) as ovulatory stimulus in
      superovulated does.
AB  - PURPOSE: To study the effects of r-hLH as ovulatory stimulus in does. METHOD: New
      Zealand does, 18 wk old, in estrus, received 25 IU of pregnant mare serum
      gonadotropin (PMSG) followed at 48 h either by 50 IU of r-hLH (n = 20) or hCG (n
      = 20) to induce follicular growth and ovulation. All does were previously
      artificially inseminated to avoid endogenous LH surge. Half of the animals
      receiving r-hLH (n = 10) or hCG (n = 10) were killed at 72 h after the hormone
      administration, and the remaining half were killed at 14 days. At 72 h the number
      of corpora lutea and preovulatory follicles was determined, and fertilization
      rate, embryo quality, degree of embryonic development, and oviductal transit were
      all assessed. On day 14 the number corpora lutea and implanted embryos were
      counted, and implantation rate was determined. Median and interquartile ranges
      were calculated for each parameter. RESULTS: At 72 h the median for corpora lutea
      was 8 (7-10) in the r-hLH group vs 13 (10-14) in the hCG group (P = 0.009);
      preopvulatory follicles were 7 (6-10) vs 0 (0-0) (P = 0.0007); the percentage of
      good-quality embryos was 71.4% (54.5-75) vs 33.3% (25-37.5) (P = 0.001), for
      intermediate-quality embryos it was 25% (14.3-36.4) vs 33.3% (25-38.5), and the
      percentage of degenerated embryos was 0% (0-12.5) vs 33.3% (25-37.5) (P = 0.015),
      respectively. Fertilization rates were similar in both groups. Embryonic
      development was more homogeneous in the animals receiving r-hLH (8 to > or = 16
      cells) compared to those receiving hCG (2 to > or = 16 cells). The median of
      embryos still in oviducts at 72 h was significantly higher in the hCG group [6 (4
      13)] than in the r-hLH group [0 (0-4)] (P = 0.41). At 14 days the median of
      corpora lutea was higher in the hCG [12 (11-16)] than in the r-hLH group [10 (7
      13)] (P = 0.008), but no differences were noted in the number of implanted
      embryos. Implantation rate was higher in the r-hLH group [100 (92.3-100)] than in
      the hCG group [87.5 (83.3-94.1)] (P = 0.056). CONCLUSIONS: At the studied dose an
      ovulatory stimulus with r-hLH induced fewer follicles to ovulate than hCG.
      Recombinant-hLH produced superior embryo morphological quality, a more
      homogeneous degree of embryo development, and more synchronous embryo transit
      than hCG. In spite of the larger number of ovulations following hCG, subsequent
      events essential for pregnancy were higher with r-hLH, offsetting differences in
      terms of implanted embryos at 14 days of pregnancy.

PMID- 7580014
TI  - Egg donation should be limited to women below 60 years of age.

PMID- 7580013
TI  - Clomiphene citrate and hMG: an alternative stimulation protocol for selected
      failed in vitro fertilization patients.
AB  - PURPOSE: This study was carried out to evaluate the potential role of the
      combination clomiphene citrate/human menopausal gonadotropin (CC/hMG) for
      patients who failed previous in vitro fertilization (IVF) attempts with
      gonadotropin-releasing hormone analogs (GnRH-a) and/or exogenous gonadotropins.
      METHODS: Patients were stimulated with CC/hMG (n = 93) after unsuccessfully
      undergoing 182 gonadotropin cycles with (n = 106) or without (n = 76) luteal
      phase GnRH-a. Cancellation rate, length of stimulation, and peak estradiol levels
      did not differ significantly between the two regimens. RESULTS: Although fewer
      oocytes were retrieved when the CC/hMG combination was used, 16 patients were
      able to successfully achieve a pregnancy (26.2% delivery rate/transfer). When
      daily follicle stimulating hormone (FSH) levels were measured in two successive
      cycles in those women who conceived with the CC/hMG stimulation, baseline levels
      did not differ when compared with a previous GnRH-a/hMG cycle. Nevertheless,
      serum FSH levels rose rapidly and remained higher in the GnRH-a/hMG cycle,
      reaching significantly higher levels on day of human chorionic gonadotropin (hCG)
      administration. CONCLUSION: Selected patients who failed previous IVF attempts
      with gonadotropins with or without GnRH analogs may benefit from the addition of
      CC to their ovarian stimulation protocol.

PMID- 7580011
TI  - Identification of biologically active inhibin in the peritoneal fluid of women.
AB  - PURPOSE: Immunoreactive inhibin (i-inhibin) has been reported to be present in
      the peritoneal fluid of women. The radioimmunoassay employed measures free,
      biologically inactive alpha-subunits(s) equally as well as dimeric, biologically
      active inhibin. The present study was designed to determine if biologically
      active, dimeric inhibin is present in the peritoneal fluid of women. METHODS:
      Peritoneal fluid of four women was assayed by radioimmunoassay, a sheep pituitary
      bioassay, and two ELISA procedures which utilized specific monoclonal antibodies
      for the "capture" of the alpha-subunit (ELISA-A) or the beta-subunit (ELISA-B) of
      inhibin and subsequent quantification of dimeric inhibin-A. RESULTS: There was a
      good correlation between the values obtained by radioimmunoassay, bioassay, and
      both ELISAs; two samples (from the late follicular phase) with relatively high i
      inhibin concentrations were positive in all four assays, whereas two samples
      (from the early follicular phase) with very low i-inhibin concentrations were
      negative in the bioassay and ELISAs. CONCLUSION: A significant portion of the
      immunoreactive inhibin in the peritoneal fluid obtained during the late
      follicular phase of women is dimeric, biologically active inhibin. We speculate
      that this may have potential implications for oocyte maturation and early
      embryogenesis within the oviduct.

PMID- 7580016
TI  - Oocyte donation.

PMID- 7580015
TI  - The upper age limit for egg donation recipients.

PMID- 7580017
TI  - The human menopausal gonadotropin (hMG) dose in in vitro fertilization (IVF):
      what is the optimal dose?

PMID- 7580018
TI  - Low- versus high-dose human menopausal gonadotropin in an in vitro fertilization
      embryo transfer program.

PMID- 7580020
TI  - The predictive value of basal follicle stimulating and growth hormone levels as
      determined by immunofluorometry during assisted reproduction.
AB  - PURPOSE: Our purpose was (a) to investigate relationships of baseline endocrine
      serum levels with selected assisted reproduction (AR) parameters and (b) to
      evaluate the clinical applicability of an immunofluorometric assay (IFMA) as an
      alternative to a radioimmunoassay (RIA). METHODS: Basal endocrine values
      (analyzed by RIA-rFSH, rLH, and rE2; analyzed by IFMA-fFSH, fLH, and fGH) were
      determined for female patients (n = 142) preceding ovarian stimulation for AR.
      RESULTS: Specific AR parameters correlated significantly with RIA- and IFMA
      determined FSH levels, although IFMA correlations consistently exceeds that of
      RIA. Cut-off values of fFSH > or = 11.68 IU/L or rFSH > or = 15.0 IU/L indicated
      a poor response. The high-basal fFSH group was older (34 vs 31 years; P = 0.0334)
      and yielded fewer oocytes (2.9 vs 4.6 oocytes; P = 0.0018) than the low-basal
      fFSH group (< 11.68 IU/L). Lower cumulative embryo scores and conception rates
      were also associated with the high-fFSH group, compared to the low-fFSH group.
      CONCLUSIONS: This study confirms the negative impact of elevated basal FSH levels
      on AR. Basal LH, GH, and E2 levels are, in comparison to baseline FSH levels,
      unsuitable indices for estimating ovarian responsiveness. IFMA can be regarded as
      an alternative to RIA in both clinical and research laboratories.

PMID- 7580019
TI  - Developmental potential of frozen-thawed human blastocysts.
AB  - PURPOSE: To examine the possibility of freezing human embryos at late cleaved
      stages (morula or blastocyst stage), we cryopreserved human embryos 5 days (day
      5) or 6 days (day 6) after insemination and investigated their developmental
      potential after thawing. MATERIALS AND METHODS: One hundred nineteen
      morphologically good-quality human embryos from 43 women undergoing in vitro
      fertilization treatment between 1991 and 1992 were frozen using dimethylsulfoxide
      as a cryoprotectant. The embryos were cryopreserved for 5 to 30 months. After
      thawing they were then cultured in vitro for 24 hr to investigate their
      developmental potential. Survival rates and developmental rates were
      morphologically assessed after 24 hr of in vitro culture. RESULTS: Developmental
      rates were significantly (P < 0.01 or P < 0.05) lower than survival rates at
      every developmental stage. There was no difference in total survival rates
      between embryos frozen 5 days after insemination (78.2%; 54/69) and embryos
      frozen 6 days after insemination (70.0%; 35/54). However, the developmental rates
      after 24 hr of culture was significantly (P < 0.05) lower for embryos frozen 6
      days after insemination (6.0%; 3/50) than for embryos frozen 5 days after
      insemination (18.8%; 13/69). Only two embryos developed into fetuses after
      transfer into the uterus (1.7%; 2/119). CONCLUSIONS: From the results, the
      developmental potential of frozen-thawed human blastocysts was found to be
      significantly reduced, even though the blastocysts were of morphologically good
      quality. Longer in vitro exposure of embryos appears to reduce their
      developmental potential.

PMID- 7580021
TI  - Use of buserelin and low-dose human menopausal gonadotropin for in vitro
      fertilization in women at risk of ovarian hyperstimulation syndrome.
AB  - PURPOSE: The purpose of the present study was (i) to assess the value of using a
      low dose of hMG (75 IU/day) to achieve ovarian stimulation in women who have
      previously shown an exaggerated response to a standard dose of 150 IU human
      menopausal gonadotropin/day in a desensitization (group I) or flare-up (group II)
      protocol and (ii) to determine whether the choice of GnRH-a regimen in a
      subsequent cycle, namely, a desensitization or flare-up protocol, influenced the
      effectiveness of the low dose of hMG. RESULTS: In group I, 75% (12/16) and 57%
      (8/14) of the subsequent desensitization and flare-up protocols, respectively,
      were cancelled because of inadequate ovarian response. Similarly, the
      cancellation rates in group II were 10 of 10 and 7 of 11 (64%), respectively. The
      total cancellation rate (groups I and II together) with the desensitization
      protocol was higher than that using the flare-up protocol (P < 0.05). CONCLUSION:
      The simple use of a reduced dose of hMG (75 IU/day) for subsequent in vitro
      fertilization in women to minimize the risk of the development of ovarian
      hyperstimulation is of limited benefit since a large proportion then shows an
      inadequate response. This is particularly pronounced with a subsequent
      desensitization protocol which does not utilize endogenous gonadotropins to
      initiate follicular development.

PMID- 7580022
TI  - Second polar body extrusion is highly predictive for oocyte fertilization as soon
      as 3 hr after intracytoplasmic sperm injection (ICSI).
AB  - OBJECTIVE: Our objective was to evaluate the time course and the predictive value
      of the extrusion of the second polar body after intracytoplasmic injection (ICSI)
      related to the fertilization rate, embryo cleavage and quality. SETTING: The
      setting was the in vitro fertilization program of a university hospital.
      PATIENTS: Twenty-one patients were treated with intracytoplasmic single sperm
      injection either for fertilization failure in IVF, low fertilization in IVF (<
      5%), or severe male factors. DESIGN: One hundred thirty-five of 205 metaphase 2
      oocytes treated with intracytoplasmic single sperm injection were observed 1, 2,
      and 3 hr after the assisted fertilization procedure. Extrusion of the second
      polar body was recorded. For each of these oocytes, fertilization was noted 18 hr
      after ICSI and cleavage and embryo quality were assessed 24 hr later. The 70
      remaining oocytes were used to assess a possible negative effect of repeated
      exposure to light microscopy. RESULTS: The extrusion of the second polar body 3
      hr after injection was an observation with a sensitivity of 0.87, a specificity
      of 0.58, and a high positive predictive value (0.90) toward oocyte fertilization.
      Twenty-nine and four-tenths percent of the oocytes extruded a second polar body
      within the first hour, 56.6% within the first 2 hr, and 78.3% had a second polar
      body 3 hr after injection. This time course was related neither to the speed of
      embryo cleavage nor to the embryo quality. Fertilization, cleavage, and embryo
      quality were not affected by repeated observation as deduced from comparison with
      the control group and confirmed by a high pregnancy (62% per oocyte retrieval)
      and implantation rate (22% per replaced embryo). CONCLUSION: Oocytes can be
      checked, in all safety, 3 hr after a single sperm injection for the presence of a
      second polar to predict oocyte fertilization with a high certainty.

PMID- 7580025
TI  - Influence of thyroxine on human granulosa cell steroidogenesis in vitro.
AB  - PURPOSE: The objective of this study was to investigate the influence of thyroid
      hormone on estradiol and progesterone secretion of human granulosa cells
      maintained in vitro. METHODS: Granulosa cells were obtained by aspiration of
      preovulatory follicles of woman undergoing assisted reproductive technology.
      Ovulation induction was performed with GnRH agonist, hMG, and hCG. RESULTS:
      Granulosa cells were maintained in vitro in a defined medium with added insulin.
      Twenty-four-hour estradiol and progesterone secretion into the medium were
      determined for granulosa cells growing in serum-free medium and in serum-free
      medium with added T4 in a concentration range of 10(-7) to 10(-11) M.
      CONCLUSIONS: All concentrations of T4 used produced a statistically significant
      increase in progesterone secretion (range, 1.39 to 1.60 times the baseline
      amount). The increase in estradiol secretion reached statistical significance
      only at a T4 concentration of 10(-8) M (1.24 times the baseline amount).

PMID- 7580023
TI  - Involvement of ovarian factors magnified by pharmacological induction of multiple
      follicular development (MFD) in the increase in Ca125 occurring during the luteal
      phase and the first 12 weeks of induced pregnancies.
AB  - OBJECTIVE: To evaluate the relationship of ovarian activity on Ca125 production,
      we studied whether Ca125 production varies during the menstrual cycle both in
      normal ovulatory women and in women whose ovarian factors are significantly
      stimulated by multiple follicular development (MFD). Furthermore, since the first
      12 weeks of pregnancy is characterized by the enhancement of corpus luteum
      function mainly in MFD-induced pregnancies, Ca125 levels were also evaluated in
      the first quarter of pregnancy both in spontaneous and in MFD-induced
      pregnancies. SUBJECTS: Subjects were normal ovulatory women in the late
      follicular phase (FP) (N = 20) and in the luteal phase (LP) (N = 20), 32
      infertile women submitted to MFD with pure FSH, and 40 pregnant women in which
      pregnancy occurred spontaneously (N = 20) or after induction of MFD (N = 20).
      RESULTS AND CONCLUSIONS: In regularly cycling women plasma Ca125 levels were
      constant during the menstrual cycle. In contrast, in stimulated cycles Ca125
      levels were significantly higher (P < 0.0008) in the LP than in the FP. In
      addition, in these subjects Ca125 levels in the LP were significantly correlated
      (P < 0.0001, r = 0.686) with E2 plasma levels. These data strongly suggest that
      an increase in corpus luteum function could be involved in Ca125 production.
      Since granulosa cells have not been demonstrated to produce Ca125, it can be
      hypothesized that endometrial or peritoneal cells submitted to exaggerated
      stimulation by ovarian activity are the source of increased Ca125 secretion. In
      agreement with this hypothesis, Ca125 levels were significantly higher in the
      first weeks of spontaneous pregnancies than in the luteal phase and they were
      also higher in MFD-induced pregnancies than in spontaneous pregnancies (P <
      0.001).

PMID- 7580024
TI  - In vitro maturation and fertilization of oocytes isolated from aged mice: a
      strategy to rescue valuable genetic resources.
AB  - PURPOSE: This project was to determine whether oocytes isolated from virgin aged
      mice, up to 18 months old, are competent to undergo cytoplasmic maturation in
      vitro and undergo fertilization and embryonic development. If so, oocyte
      maturation in vitro could be used as a strategy to rescue valuable genetic
      resources. RESULTS: Although the number of oocytes recovered from mice was
      greatly reduced with increasing age, the percentage of oocytes that underwent
      fertilization, cleavage, and development to the blastocyst stage was essentially
      unchanged up to 18 months of age. The success of cleavage to the two-cell stage
      was greater after maturation in vitro (81%) than gonadotropin-induced maturation
      in vivo (55%). About 20% (20/106) of the embryos derived from oocytes isolated
      from 18-month-old mice developed to term after embryo transfer. CONCLUSION:
      Oocytes from virgin aged mice undergo normal cytoplasmic maturation in vitro.
      Higher percentages of oocytes from aged mice cleave to the two-cell stage after
      spontaneous maturation in vitro than after gonadotropin-induced maturation in
      vivo. Therefore, in vitro maturation and fertilization of oocytes could be used
      to rescue valuable genetic resources that might otherwise be lost because of age
      related infertility.

PMID- 7580026
TI  - Factors related to early pregnancy recognition in the woman.
AB  - PURPOSE: While the precise timing of the maternal recognition of pregnancy is not
      known, it is known that the prevention of return to ovarian cyclicity relies on a
      conceptus-derived signal. METHODS: In an attempt to identify the first
      luteotropic signals detectable in the maternal circulation, a sensitive Leydig
      cell luteotropin bioassay was employed, and data were compared for nine
      clinically pregnant and nine nonpregnant patients in an in vitro fertilization
      program. Blood samples were drawn every other day for 10 days after embryo
      transfer (ET). RESULTS: The first detectable rise in bioactive luteotropin levels
      occurred between 6 and 8 days post ET. Serum E2 levels increased on the same
      days. Differences in luteotropin levels between pregnant and nonpregnant patients
      were significant between days 6 and 8 (P < 0.0001) and between days 8 and 10 (P <
      0.002). CONCLUSIONS: Based on morphological studies reported by others, bioactive
      luteotropic signals identified in this study were detectable in the maternal
      circulation at about the time of trophoblast lacunae coalescing with maternal
      uterine blood vessels.

PMID- 7580027
TI  - The effect of alpha-amylase on the acrosomal membrane of human sperm.
AB  - PURPOSE: Sperm capacitation and the acrosome reaction are prerequisites to
      accomplishing fertilization. The object of this research was to induce
      capacitation and the acrosome reaction of human sperm, comparing the acrosome
      status of fertile and infertile men, using alpha-amylase. METHODS: Acrosome
      status was measured using indirect immunofluorescence (IIF; monoclonal antibody
      GB24, Theramex), hemizona assay (HZA), and transmission electron microscopy
      (TEM). RESULTS: Acrosome-reacted sperm without alpha-amylase treatment was
      significantly more abundant in the fertile versus the infertile group utilizing
      IIF, HZA, and TEM. alpha-Amylase-treated spermatozoa from the fertile and
      infertile groups showed a significant increase in the number of sperm bound to
      the hemizona (P < 0.05). CONCLUSIONS: The percentage of acrosome-reacted sperm in
      the infertile group was significantly enhanced by alpha-amylase, utilizing IIF
      and TEM.

PMID- 7580028
TI  - Assisted hatching in mouse embryos using a noncontact Ho:YSGG laser system.
AB  - PURPOSE: A noncontact holmium:yttrium scandium gallium garnet (Ho:YSGG) laser
      system has been designed and tested for the micromanipulation of mammalian
      embryos. The purpose of this preliminary investigation was to determine the
      effectiveness of this laser for assisted hatching and evaluate its impact on
      embryo viability. The Ho:YSGG system, utilizing 250-microsecond pulses at a
      wavelength of 2.1 microns and 4 Hz, was used to remove a portion of the zona
      pellucida (ZP) of two- to four-cell FVB mouse embryos. RESULTS: In the first
      experiment there was no difference in blastocyst production or hatching rates
      following laser or conventional assisted hatching (LAH or AH, respectively) in
      contrast to control embryos cultured in a 5% CO2 humidified air incubator at 37
      degrees C. In the second experiment a blastocyst antihatching culture model was
      employed and LAH-treated embryos were cultured in a serum-free HTF medium (HTF
      o). Blastocyst formation was not influenced by LAH treatment and hatching was
      increased (P < 0.01) from 4 to 60% compared to HTF-o control group. CONCLUSIONS:
      These preliminary data demonstrate the utility and nontoxic properties of the
      Ho:YSGG laser system for quick and precise ZP drilling.

PMID- 7580029
TI  - Successful pregnancy in a bone marrow transplant recipient following oocyte
      donation.
AB  - We describe the successful establishment of pregnancy in a woman status post-bone
      marrow transplantation using assisted reproduction. Oocyte donation offers women
      with gonadal failure secondary to cytotoxic agents a reasonable chance at child
      bearing.

PMID- 7580030
TI  - A relationship between availability of school nurses and child well-being.

PMID- 7580032
TI  - Development of a health concerns inventory for school-age children.
AB  - The purpose of this study was to examine the validity and reliability of the
      "School Age Health Concerns Inventory" developed by the authors. A national
      sample of students in third to sixth grades was assessed by school nurses using
      this instrument. Each student's responses were verified in a short interview with
      the school nurse. The instrument was evaluated on the basis of ease of use,
      language, and effectiveness in identifying students who need health services.

PMID- 7580031
TI  - A university's response to a need for school nurse education.
AB  - This study examined the need for program development that allows school nurses
      the opportunity to receive advanced practice education while continuing to work
      in their school settings. Findings suggest that school nurses can advocate for
      greater access to undergraduate, graduate, and practitioner programs by
      influencing academic institutions to provide appropriate professional education
      to their members.

PMID- 7580033
TI  - Management of severe food allergy in the school setting.
AB  - Almost everyone responsible for the care of children will be dealing with food
      allergies. More children and adolescents die annually from food-induced
      anaphylaxis than from insect stings. Studies show that the majority of accidental
      ingestions resulting in death occur at school. This clearly indicates the need
      for school health care systems to develop a mechanism to deal with such medical
      emergencies. Education and planning are key to school management of food allergy.

PMID- 7580034
TI  - Management of ADHD in the school setting--a case study.
AB  - This article describes one case study, reviews common therapies for Attention
      Deficit Hyperactivity Disorder (ADHD), and presents specific approaches a school
      nurse may take in addressing the symptoms of ADHD. Use of a conceptual model
      provides the framework to interpret data and proposed nursing therapies.

PMID- 7580035
TI  - Is it stress?

PMID- 7580037
TI  - Imipramine.

PMID- 7580036
TI  - Health software for school nurses.

PMID- 7580038
TI  - Incidence and hospital mortality of acute coronary artery disease among civilians
      in Zagreb during air-raid alarms.
AB  - During the period of air-raid alarms in Zagreb (September 1991), the influence of
      war-induced stress on the incidence and mortality of acute coronary artery
      disease was investigated. Control periods were September 1989 and September 1990.
      Among 2903 patients admitted to Emergency Care Units, 369 (13%) were examined for
      suspect acute coronary artery disease. During the same periods in 1989 and 1990,
      10% and 11% of acute coronary artery disease patients were recorded,
      respectively. The percentage of patients with myocardial infarction or unstable
      angina, admitted to Coronary Care Units during September 1989, 1990 and 1991, was
      49%, 50% and 55%, respectively. The number of Q myocardial patients admitted
      during September 1991 was significantly higher than that recorded during the same
      period in 1990. The incidence and mortality patterns in acute coronary artery
      disease patients were also examined during August, September and October 1991.
      The peak incidence of acute coronary artery disease was found in the first half
      of September, while the peak mortality in these patients was found during the
      second half of September. During the second half of September of 1989, 1990 and
      1991, the mortality in Q myocardial patients in Coronary Care Units, was 16.7%,
      15.2% and 23.8%, respectively. Besides the war-induced stress, transportation of
      our patients to shelters or inner parts of the hospital caused additional stress,
      probably contributing to the development of refractory malignant arrhythmia or
      heart failure.

PMID- 7580039
TI  - Clinical experience with short-time hemodialysis.
AB  - To determine the safety and efficiency of short-time hemodialysis (HD), the
      authors used the urea kinetic method to provide patients with similar amount of
      dialysis to that received during conventional treatment times. After six months
      on conventional HD (cellulosa acetate dialyzers, bicarbonate dialysate, and 4
      hour treatment time), 8 patients were switched to short-time HD (cellulose
      triacetate dialyzers, bicarbonate dialysate, and 3-hour treatment time). During
      short-time HD, treatment time was reduced by 25%, while Kt/V index and protein
      catabolic rate remained constant. Shorter treatment times were not associated
      with an increase in intra- or interdialytic complications. When compared with the
      conventional period, short-time HD did not result in pre- or postdialysis blood
      pressure changes, interdialytic weight gain, or changes in biochemical
      parameters. Short-time HD did not result in an increase in hospital admissions.
      This study demonstrates that short-time HD performed with mandatory attention to
      the adequacy of dialysis as measured by urea kinetic modeling is compatible with
      objective improvement in patient welfare. The long-term effects of this treatment
      modality are not known, but our experience so far has been favorable.

PMID- 7580040
TI  - Giant peptic ulcers in patients undergoing maintenance hemodialysis.
AB  - The aim of the study was to investigate the clinical characteristics of
      hemodialyzed uremic patients with upper gastrointestinal lesions. A total of 20
      (7.2%) out of 276 patients on hemodialysis program underwent endoscopy and
      rentgenography of the upper gastrointestinal tract. The incidence of peptic ulcer
      disease in the patients with end-stage renal disease was 4.3%. Six (30%) out of
      20 uremic hemodialyzed patients with gastrointestinal complications had giant
      peptic ulcers of duodenum or prepyloric area. In three (50%) out of six subjects,
      giant peptic ulcers were located in the second portion of the duodenum.
      Gastrointestinal hemorrhagic complications occurred in 12 (60%) patients. The
      most frequent sources of bleeding were duodenal ulcers alone (8 patients) or in
      combination with gastric and/or duodenal flat erosions (6 patients),
      angiodysplasia of the duodenum (3 patients) and duodenal erosions (one patient).
      Two patients with bleeding from giant ulcers died from perforation and
      hemorrhagic shock. The uremic hemodialyzed patients with giant ulcers were older
      than 65, had higher basal gastrin concentration (305.3 +/- 183.8 pmol/l), and
      lower basal (1.6 +/- 0.16 mmol/h) and stimulated gastric acid secretion (14.4 +/-
      8.63 mmol/h).

PMID- 7580041
TI  - Treatment of war injuries to the colon: primary resection and anastomosis without
      relieving colostomy.
AB  - Fourteen casualties with penetrating injuries to the colon caused by firearms in
      combat zones have been treated according to the principles accepted today for the
      treatment of such injuries acquired in civilian violence. The patients were
      treated by primary resection of the injured part of the intestine, without
      relieving colostomy, providing that the time interval between the moment of
      injury and admittance to the hospital was less than six hours. Ten patients
      fulfilled this criterion, while three patients with prolonged time intervals were
      treated by resection and colostomy, and one by exteriorization. Overall mortality
      was 14.3%, and correlated to the injury severity score. Complications related to
      colon surgery occurred in one patient (7%). Primary resection without relieving
      colostomy for the colon injuries caused by firearms is a safe procedure providing
      that the time interval between wounding and surgery does not exceed six hours.

PMID- 7580042
TI  - Helicobacter pylori in a group of endoscopically examined patients in the county
      of Medimurje.
AB  - The presence of Helicobacter pylori was investigated in 50 patients, mean age 54
      years and age range 28-56 years. Gastroduodenoscopy and biopsy of the antral
      and/or pyloric part of gastric mucous membrane were performed in all study
      patients. Bioptic tissue was examined by culture and histologic staining, and
      tested by a rapid urease test. According to overall results, the urease test was
      most sensitive, i.e. positive in 23 (45%) patients, whereas histological staining
      was positive in 14 (29) patients. Endoscopic diagnosis revealed the following:
      duodenal ulcer--histologic stain 3/5 (55%), urease test 9/21 (43%); gastric
      erosion--histologic stain 4/13 (31%), urease test 7/13 (55%); gastroduodenitis-
      histologic stain and urease test 2/4 (50%). According to endoscopy, positive
      pyloriset test (Orion Diagnostica) was found as follows: duodenal ulcer 5/7
      (71%), gastric ulcer 8/10 (80%), gastric erosion 10/12 (83%) and gastroduodenitis
      5/7 (71%). The authors recommend the diagnosis of Helicobacter pylori as a
      routine approach in gastroenterological routine.

PMID- 7580043
TI  - Schizophrenic disorder in old age. I. Some demographic, social and clinical
      characteristics.
AB  - This study discussed 129 cases who were at the time of the investigation 65 years
      of age and older, and in whom during their life-time schizophrenic disorder was
      diagnosed. Using a modified P-86 questionnaire and SCAG scale, heteroanamnestic
      data and data available from the patients' medical histories, demographic,
      social, and clinical characteristics of this population were gathered. Among
      other things, the article shows that the present marital status is the result of
      psychiatric illness, that the trend of social upward mobility exists in this
      population as well, and that lesions of the sphere of interest are the result of
      the psychiatric disorder, while the lesions of the sphere of initiative are the
      consequences of ageing process. It is also found that in correlation with age the
      clinical picture of the schizophrenic disorder becomes less "clear", and that a
      trend of co-existence of affective disorders is present.

PMID- 7580044
TI  - Schizophrenic disorder in old age. II. Some differences in demographic, social
      and clinical characteristics in terms of place of permanent residence.
AB  - The author examined 129 cases who were at the time of the investigation 65 years
      of age and older and who, during their life-time, had been diagnosed as having a
      schizophrenic disorder. Using a modified P-86 questionnaire and SCAG scale,
      heteroanamnestic data, and data available from medical histories, the
      demographic, social, and clinical characteristics of this population were
      gathered. Differences were defined in terms of the examinees' place of permanent
      residence (at home, in hospital, in a retirement home). Among other things, the
      author shows that the type of the permanent residence corresponds to the
      severeness of the psychiatric disorder, that 1/3 of the sample is completely
      socially isolated, and that life in the retirement home has a very beneficial
      influence on the mental health of elderly patients. On the other hand, the
      question is raised whether the quality of the psychiatric care in the retirement
      homes is good enough.

PMID- 7580045
TI  - Schizophrenic disorder in old age. III. Some demographic, social and clinical
      differences between schizophrenic disorder with early and late onset.
AB  - For this study the author examined 129 cases who were 65 years of age and older
      at the time of investigation, and who had been diagnosed as having schizophrenic
      disorder during their lifetime. Using a modified P-86 questionnaire and SCAG
      scale, heteroanamnestic data, and data available from medical histories, the
      demographic, social and clinical characteristics of this population were
      gathered. Differences were defined in regards to the above-mentioned
      characteristics, between the examinees whose age at the time of the onset of
      illness was less than 45 and those who were older. Among other things, it is
      evidenced that males have an earlier onset of illness, that regardless of the age
      at the onset of illness the present clinical picture in old age is almost equal,
      and that the examinees do not differ in terms of the average number of
      hospitalizations, their duration, the time-span between them, nor any co-existing
      organic mental disorder.

PMID- 7580046
TI  - Idiopathic osteonecrosis of the humeral head.
AB  - According to the frequency of occurrence, osteonecrosis of the humeral head ranks
      immediately after osteonecrosis of the femoral head. Experimental and clinical
      studies have indicated one or more mechanisms acting alone or in combination and
      causing necrosis of the bone. Rare cases in which the cause of osteonecrosis
      remains unknown, are referred to as the idiopathic form of humeral head
      osteonecrosis. The authors discuss the most recent advances in the
      etiopathogenesis of osteonecrosis, classification of humeral head osteonecrosis,
      and the methods of treatment. Three patients are described: two suffering from
      the idiopathic form and one with osteonecrosis of the humeral head related to an
      unidentified process affecting the condyles of the knee and both calcanei, and
      characterized by condensation of the bone.

PMID- 7580047
TI  - Pyoderma gangrenosum.
AB  - The authors summarize recent data on the etiopathogenesis and therapy of pyoderma
      gangrenosum and report on a 72-year-old patient for years suffering from
      recurring nodose lesions on his forelegs. The ulcerations first appeared a month
      before the patient's admission to author's Department. The course of the disease,
      patient's history and comprehensive clinical and laboratory findings pointed to
      the diagnosis of pyoderma gangrenosum. The patient was treated with systemic
      application of corticosteroids, and this therapy proved very effective.

PMID- 7580048
TI  - Evaluation of malondialdehyde as an index of lead damage in rat brain
      homogenates.
AB  - Lipid peroxidation in vitro homogenates of brain was examined as sequela of lead
      toxicity. The levels of malondialdehyde (MDA) in homogenates of rat brain (1 ml,
      5% w/v) treated with lead (50 micrograms) alone or in combination with ascorbic
      acid (100 micrograms), alphatocopherol (100 micrograms) or hydroquinone (100
      micrograms) were evaluated. The levels of MDA were consistently evoked by lead in
      a dose-related manner. The toxicity of lead was further advanced by the action of
      the pro-oxidant drug ascorbic acid on the brain. However, the anti-oxidant drugs
      alphatocopherol and hydroquinone decreased the toxic effect of lead on the brain.
      These results clearly show that the enhanced lipid peroxidation may provide a
      basis of lead-induced neurotoxicity.

PMID- 7580049
TI  - Modified nucleoside-dependent transition metal binding to DNA analogs of the tRNA
      anticodon stem/loop domain.
AB  - Biologically active DNA analogs of tRNAPhe (tDNAPhe) were used to investigate
      metal ion interaction with tRNA-like structures lacking the 2'OH. Binding of Mg2+
      to the 76 oligonucleotide tDNAPhe, monitored by circular dichroism spectroscopy,
      increased base stacking and thus the conformational stability of the molecule.
      Mg2+ binding was dependent on a d(m5C) in the anticodon region. In contrast to
      Mg2+, Cd2+ decreased base stacking interactions, thereby destabilizing the
      molecule. Since alterations in the anticodon region contributed to most of the
      spectral changes observed, detailed studies were conducted with anticodon hairpin
      heptadecamers (tDNAPheAC). The conformation of tDNAPheAC-d(m5C) in the presence
      of 1 mM Cd2+, Co2+, Cr2+, Cu2+, Ni2+, Pb2+, VO2+ or Zn2+ differed significantly
      from that of the biologically active structure resulting from interaction with
      Mg2+, Mn2+ or Ca2+. Nanomolar concentrations of the transition metals were
      sufficient to denature the tDNAPheAC-d(m5C) structure without catalyzing cleavage
      of the oligonucleotide. In the absence of Mg2+ and at [Cd2+] to [tDNAPheAC
      d(m5C)] ratios of approximately 0.2-1.0, tDNAPheAC-d(m5C40) formed a stable
      conformation with one Cd2+ bound with a Kd = 3.7 x 10(-7) M. In contrast to Mg2+,
      Cd2+ altered the DNA analogs without discriminating between modified and
      unmodified tDNAPheAC. This ability of transition metals to disrupt higher order
      DNA structures, and possibly RNA, at microM concentrations, in vitro,
      demonstrates that these structures are potential targets in chronic metal
      exposure, in vivo.

PMID- 7580051
TI  - Ornibactin production and transport properties in strains of Burkholderia
      vietnamiensis and Burkholderia cepacia (formerly Pseudomonas cepacia).
AB  - Several strains of Burkholderia vietnamiensis, isolated from the rhizosphere of
      rice plants, and four strains formerly known as Pseudomonas cepacia including two
      collection strains and two clinical isolates were compared for siderophore
      production and iron uptake. The B. vietnamiensis (TVV strains) as well as the B.
      cepacia strains (ATCC 25416 and ATCC 17759) and the clinical isolates K132 and
      LMG 6999 were all found to produce ornibactins under iron starvation. The two
      ATCC strains of B. cepacia additionally produced the previously described
      siderophores, pyochelin and cepabactin. Analysis of the ratio of isolated
      ornibactins (C4, C6 and C8) by HPLC revealed nearly identical profiles.
      Supplementation of the production medium with ornithine (20 mM) resulted in a 2.5
      fold increase in ornibactin synthesis. Ornibactin-mediated iron uptake was
      independent of the length of the acyl side chain and was observed with all
      strains of B. vietnamiensis and B. cepacia, but was absent with strains of
      Pseudomonas aeruginosa, Pseudomonas fluorescens and Pseudomonas stutzeri, known
      to produce pyoverdines or desferriferrioxamines as siderophores. These results
      suggest that ornibactin production is a common feature of all Burkholderia
      strains and that these strains develop an ornibactin-specific iron transport
      system which is distinct from the pyoverdine-specific transport in Pseudomonas
      strains.

PMID- 7580050
TI  - Whole-body retention, and urinary and fecal excretion of mercury after subchronic
      oral exposure to mercuric chloride in rats.
AB  - The effects of long-term daily intake of mercury on its urinary and fecal
      excretion, whole-body retention, and blood concentration in male rats were
      observed. The animals were exposed to mercuric, chloride labeled with 203Hg via
      drinking water for 8 weeks (5, 50 and 500 microM Hg). 203Hg in urine, feces and
      blood was quantified. The blood mercury concentration did not keep a linear
      relationship with the increasing dose. The percentage of the total amount of
      mercury intake which is excreted by the fecal route in rats exposed to 500 microM
      Hg was significantly lower than in those exposed to 5 and 50 microM. The daily
      dose percentage of mercury excreted in urine increased with dose size. The
      results show that the absorption fraction of mercury through the gastrointestinal
      tract (30-40%) was higher than values previously reported.

PMID- 7580053
TI  - A kinetic study of the coupled iron-ceruloplasmin catalyzed oxidation of
      ascorbate in the presence of albumin.
AB  - Ascorbate is catalytically oxidized by a couple iron-ceruloplasmin system, the
      iron ions functioning as a red/ox cycling intermediate between ceruloplasmin and
      ascorbate. Serum albumin, an iron binding compound, was found to stimulate the
      ascorbate oxidation rate. It is proposed that ferrous ions react more rapidly
      with ceruloplasmin when they are bound to albumin. A Km value of 39 microM was
      estimated for Fe(2+)-albumin. Citrate and urate inhibit the iron-ceruloplasmin
      dependent ascorbate oxidation by chelating ferric ions. In the presence of
      albumin only citrate reduced the oxidation rate, the observation suggesting the
      following order of iron binding ability: citrate > albumin > urate. Physiological
      aspects of the results have been discussed.

PMID- 7580052
TI  - Proferrioxamine synthesis in Erwinia amylovora in response to precursor or
      hydroxylysine feeding: metabolic profiling with liquid chromatography
      electrospray mass spectrometry.
AB  - Metabolic profiling by capillary liquid chromatography-electrospray mass
      spectrometry was used to monitor shifts in the proferrioxamine profiles of
      Erwinia amylovora in response to externally supplied potential proferrioxamine
      precursors, selected stable-isotope-labeled precursors and atypical precursors.
      Based on the qualitative and quantitative shifts in the proferrioxamine profiles,
      lysine and arginine are unambiguous, and agmatine, ornithine, diaminobutyric acid
      and the corresponding C3-5 diamines are highly likely precursors for
      proferrioxamine biosynthesis in E. amylovora. 5-Hydroxylysine (Hyl), a recently
      discovered growth inhibitor for E. amylovora, suppresses proferrioxamine
      production. The Hyl-induced growth inhibition can be reversed by basic amino
      acids. The basic amino acids also partly restore proferrioxamine synthesis.

PMID- 7580055
TI  - An in vitro study on the binding of Al(III) to human serum transferrin with the
      isoelectric focusing technique.
AB  - Transferrin saturated with Al3+ subjected to isoelectric focusing (IEF) in a pH
      gradient can be separated into four fractions, representing the apotransferrin,
      transferrin with aluminum at the metal binding site in the C- or N-terminal lobe,
      or both. The electrophoretic mobilities of these four fractions are identical to
      those of the iron-transferrin counterparts. Simultaneous binding of aluminum and
      iron to transferrin can also be demonstrated. The decreased saturation after IEF
      indicates that the affinity of transferrin for aluminum is low compared with its
      affinity for iron. This effect is particularly evident when bicarbonate is used
      as the synergistic anion in the loading procedure. In contrast, loading of
      transferrin with aluminum in the presence of oxalate produces a di-aluminum
      transferrin complex that is stable during IEF.

PMID- 7580056
TI  - [Clinical study on effect of bushen jiangu capsule on postmenopausal
      osteoporosis].
AB  - The therapeutic effect of Kidney Tonifying principle and Bushen Jiangu (BSJG)
      capsule on postmenopausal osteoporosis (17 cases) was observed and compared with
      calcium treatment group (17 cases) in double-blind method. The result showed that
      3 months after treatment with BSJG capsule, the symptoms of 92.85% patients were
      improved, and 6 months after treatment, the bone density (BD) of lumbar vertebra
      of 68.8% patients was significantly higher than that of before treatment, but the
      BD of control group was lower (P < 0.05). This suggested that BSJG capsule could
      prevent and improve postmenopausal osteoporosis. The therapeutic mechanisms
      probably is improving the bone formation and declining the bone absorption.

PMID- 7580054
TI  - Expression of metallothionein genes during the post-embryonic development of
      Drosophila melanogaster.
AB  - Expression of the two Drosophila melanogaster metallothionein genes, Mtn and Mto,
      has been analyzed by in situ hybridization during post-embryonic development. Mtn
      and Mto transcripts were detected exclusively in the digestive tract of larvae,
      pupae and adults reared on standard medium. Mtn and Mto expression domains
      overlap, but each gene is also expressed at unique sites. Mtn mRNA levels are
      approximately 10 and 20 times higher than those of Mto in larvae and adults,
      respectively. Copper and cadmium ions strongly induce Mtn and Mto mRNA
      accumulation in the midgut. Zinc is a weaker inducer, acting only at high
      concentrations. Mtn gene expression is induced by these three metals in
      Malpighian tubules, while Mto gene expression in this organ is induced only by
      zinc. Iron is a poor inducer of metallothionein mRNA accumulation. Functions of
      MTN and MTO proteins in metal homeostasis and detoxification are considered.

PMID- 7580057
TI  - [Effect of Allitridi on deforming of peripheral leucocytes in patients with acute
      cerebral infarction].
AB  - To prove the effect of Allitridi in treating acute cerebral infarction, millipore
      membrane filter technique was adopted in systematically observing the blood
      rheology and the peripheral WBC filter index of 53 healthy subjects and that of
      33 patients before and after treatments, who suffered from acute cerebral
      infarction and were confirmatorily diagnosed through CT. As a result, the
      filtered index of peripheral WBC during the acute period of cerebral infarction
      rose significantly (6.1397 +/- 4.4602), and the difference was significant
      compared with that of the healthy subjects (0.8651 +/- 0.4603, P < 0.01). Having
      been treated with Allitridi, the patients' symptoms improved and at the same time
      the filtered index of WBC lowered markedly (1.6261 +/- 1.3472). The conditions of
      the patients before and after treatments were obviously different (P < 0.01). And
      also the index of the whole blood rheology improved significantly. Therefore, it
      denoted that Allitridi could effectively improve the WBC deformation and the
      whole blood rheology as well, and alleviate the clinical symptoms.

PMID- 7580058
TI  - [Clinical and experimental study on codonopsis pilosula oral liquor in treating
      coronary heart disease with blood stasis].
AB  - The effects of Codonopsis pilosula oral liquor (CPOL) on tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor (PAI) in the plasma of 25
      patients of coronary heart disease with blood stasis were studied. It has been
      shown that those patients had a significant decrease in t-PA activity (P < 0.01)
      compared to healthy subjects. After 4 weeks of CPOL therapy, platelet aggregation
      significantly decreased (P < 0.05), there was no significant difference in t-PA
      and PAI. From the results shown above, it suggested that one of the effects of
      CPOL in influencing blood coagulation was its inhibition on platelet aggregation,
      but not through the elevating of fibrinolytic activity.

PMID- 7580059
TI  - [Preliminary analysis of relationship between immunological changes and syndrome
      differentiation-typing in traditional Chinese medicine and prognosis with chronic
      idiopathic thrombocytopenic purpura].
AB  - In order to study the relationship between the basement immunological changes,
      TCM Syndrome Differentiation and prognosis, alkaline phosphates antialkaline
      phosphatase (APAAP) and ELISA assay were used to determine the T lymphocyte
      subsets, the platelet associated antibody (PAIgG, PAIgA, PAIgM) and plasma
      antiplatelet-autoantibodies (GP II b, GP III a, GP I b) in 55 chronic idiopathic
      thrombocytopenic purpura (ITP) and 53 healthy subjects as control. The results
      indicated that the immunological changes was closely related to the prognosis,
      while the TCM Syndrome Differentiation was also related to it, which denoted that
      it is significant to investigate both factors in guiding treatment and assessing
      the prognosis.

PMID- 7580060
TI  - [Relationship between syndrome types of TCM in lung neoplasm patients and
      peripheral T lymphocyte subsets, carcino-embryonic antigen].
AB  - Fifty-six cases with lung carcinoma were detected for peripheral blood T
      lymphocyte by direct staphylococcal protein A (SPA) bacterial rose ring for
      carcino-embryonic antigen (CEA) by radioimmunoassay, and the relationship between
      T lymphocyte. CEA and Syndrome of TCM was explored. The results were as
      follows:the values of OKT3, OKT4, OKT4/OKT8 were lower in the lung carcinoma than
      that in healthy subjects (P < 0.05-0.01), but OKT8 was higher (P < 0.05); The
      values of T lymphocyte lowered or increased in the order of Yin Deficiency with
      internal Heat, Qi Stagnation with blood stasis, Phlegm-Dampness in Lung, Qi-Yin
      Deficiency, but that of CEA was the highest in Qi-stagnation with blood stasis.
      There was a significant difference between all Syndrome-types of TCM and the
      healthy subjects (P < 0.01). Therefore, it is suggested that the values of
      peripheral T lymphocytes and CEA with the lung carcinoma were regarded as good
      referential parameters in reflection the condition of Deficiency in Vitality and
      Excess in Superficiality, which offered the objective evidence for the TCM
      treatment.

PMID- 7580061
TI  - [A study on effect of qingwen granule in regulating immunological function in
      infantile respiratory viral infection].
AB  - To evaluate the effect of Qing-wen Granule (QWG) on immunological function, T
      lymphocyte subsets and interferon gamma(INF-gamma) expression cells in peripheral
      blood mononuclear cells, lymphocyte transformation rate and the level of salivary
      secretory IgA (sIgA) were determined by alkaline phosphatase antialkaline
      phosphatase (APAAP) technique or 3H-TdR incorporation with lymphocyte stimulation
      index(SI) or agar single immunodiffusion in infantile respiratory viral
      infection. The results showed that the percentage of CD3, CD4, and CD4/CD8 ratio
      of patients treated with QWG for 3 days were not significantly different in
      comparing with the control group untreated with QWG (P > 0.05), but the values of
      IFN-gamma expression cell, SI and the level of sIgA were more markedly increased
      than that of control (P < 0.05). It suggested that the QWG could improve and
      regulate immune function in infantile respiratory viral infection.

PMID- 7580062
TI  - [Study on effect of polysaccharides of ginseng on peripheral blood mononuclear
      cell induced interleukin-2 production and activity of its receptors in vitro].
AB  - To study the effect of polysaccharides of Ginseng (PSG) on cellular-immunity from
      healthy subjects and patients of kidney disease, the peripheral blood mononuclear
      cell (PBMC) induced interleukin-2 (IL-2) were assayed in vitro. It was found that
      the PSG could prommote the PBMC induced IL-2 in the healthy subjects and patients
      with kidney diseases and was dose-dependent. This study revealed that PSG was
      worthwhile to be further studied as an approach of biological responsive modifier
      therepy in treating human immunodeficiency diseases.

PMID- 7580063
TI  - [Effect of thyroid immune liquor on erythrocyte immune function in patients with
      autoimmune thyroiditis].
AB  - Thirty cases of autoimmune thyroiditis (AT) were treated with thyroid immune
      liquor (TIL). The results showed that the activity of erythrocyte C3b receptor
      and erythrocyte immune adherence enhancing factor were significantly increased,
      while erythrocyte immune complex and erythrocyte immune adherence inhibiting
      factor were decreased. The thyroid microsome-antibody and thyroid globulin
      antibody were also significantly decreased. This indicates that the TIL has
      adjustive effect on humoral immunity and cellular immunity in patients with AT.

PMID- 7580065
TI  - [Effects of emodin, sennosides and rheum polysaccharides on free calcium in
      isolated rat liver cells].
AB  - The effects of emodin (EMD), sennosides (SEN) and Rheum polysaccharides (RPP) on
      the free calcium level in the isolated rat liver cells were studied with Ca2+
      level 131.60 +/- 37.79 nmol/L in the liver cells. After adding CaCl2 (2 mmol/L)
      and KCl (120 mmol/L) to liver cell suspension sequentially, the free Ca2+ levels
      were significantly elevated compared with that of the resting status (P < 0.01).
      When the liver cells were pretreated with EMD (0.037 mmol/L) for 10 min, in the
      resting status or using the above doses of CaCl2 and KCl, the free Ca2+ levels
      were significantly increased compared with that of the control groups (P < 0.01).
      On the contrary, after administration of SEN (0.046-0.092 mmol/L) and RPP (0.1
      0.2 mg/ml), the free Ca2+ levels were obviously decreased compared with that of
      the control groups (P < 0.01). Furthermore, the inhibitory effect was dose
      dependent. The opposite effects of the different active ingredients of rhubarb
      (EMD,SEN,RPP) on the free Ca2+ levels suggested that rhubarb has many kinds of
      regulatory function in the liver cells.

PMID- 7580064
TI  - [Effects of composite xueliting on four gastric ulcer models in rats and mice].
AB  - Composite Xueliting (CXLT) was found to be an effective anti-ulcer agent in four
      experimental models in rats and mice, namely, the stress restraint-induced,
      histamin-induced, salicylic acid-induced and reserpine-induced ulcers. In above
      mentioned models, CXLT (0.214-0.856 g/kg, 1/d x 5, per os) could inhibit gastric
      ulcer by 40%-63%, 48%-85%, 68%-87% and 27%-65% respectively. Among these, the
      salicylic acid-induced ulcer was more markedly inhibited. The result suggested
      that CXLT had the protective function against the gastric ulcer.

PMID- 7580066
TI  - [Effects of poria cocos on ototoxicity induced by kanamycin in guinea-pigs].
AB  - In order to prevent the ototoxicity of kanamycin (KM), the effects of Poria Cocos
      (PC) on the ototoxicity induced by KM in guinea-pigs was observed by infusing the
      PC decoction into the guinea-pigs with comparing the difference in the general
      intoxicating symptom, prayer's reflex (PR) threshold, brainstem auditory evoked
      potentials (BAEPs) and the absence rate of outer hair cells in the first turn of
      cochlea. The results suggested that the ototoxicity of KM was retarded by giving
      the PC decoction. On 7th day after given KM, PR threshold of 4,6,8 kHz in the
      medicated group and control group were 4.7 +/- 1.5 dB, 5.7 +/- 2.4 dB, 2.7 +/-
      1.2 dB and 10.5 +/- 3.2 dB, 12.1 +/- 3.7 dB, 8.5 +/- 2.7 dB respectively. BAEPs
      threshold on 13th day given KM raised 22.7 +/- 9.7 dB in the medicated group and
      51.3 +/- 14.4 dB in control group. The absence rate of outer hair cells in first
      turn of cochlea were 39.4% and 67.4% respectively. The results suggested that PC
      might be antagonistic to the ototoxicity of KM in guinea-pigs.

PMID- 7580068
TI  - [Recent development in experimental research of single Chinese medicinal herb
      with positive inotropic action].

PMID- 7580067
TI  - [Study of anti-cerebral thromboembolism injection's activity on experimental
      arterial thrombosis and its therapeutical mechanism].
AB  - Anti-Cerebral Thromboembolism Injection (ACTI), applied intravenously in
      Cattaneo's animal model of arterial thrombosis, could significantly reduce the
      weight of thrombus, blood viscosities, plasma TXB2 level and delay the
      prothrombin time, compared to control group (P < 0.05). From this trial, it was
      indicated that ACTI's reducing thrombosis action was the result of inhibiting
      aggregation and releasing of platelets through reducing whole blood viscosities
      and TXB2 level.

PMID- 7580069
TI  - The challenge of raising nursing's professional status.

PMID- 7580070
TI  - Contracts of employment, the law and the nurse.

PMID- 7580071
TI  - A critical event in tracheostomy care.
AB  - Endotracheal suctioning is a potentially hazardous procedure which should be
      performed with care and only when indicated. The use of saline instillations
      before endotracheal suctioning has little or no value. Heat and moisture
      exchangers are effective and provide efficient humidification for artificial
      airways. More research is required into the timing of tracheostomy tube changes.
      Blockages in tracheostomy tube should be a preventable occurrence.

PMID- 7580072
TI  - Ear syringing: a clinical skill.
AB  - Ear syringing is performed by nurses in various care settings. Nurses must ensure
      that this skill is practised safely. An understanding of the ear's structure and
      functions must be applied when carrying out this procedure.

PMID- 7580073
TI  - Counselling the overdose patient in casualty.
AB  - This article investigates the competency of casualty nurses in counselling
      overdose patients. Significant differences exist between nurses' competence in
      counselling an overdose patient as opposed to other patients. Examination of a
      study raises doubts concerning the casualty nurse's competence in counselling
      overdose patients. Its implications for theory and practice are outlined.

PMID- 7580074
TI  - The giving of information is the key to family empowerment.

PMID- 7580076
TI  - Children who care: a case for nursing intervention?
AB  - A large number of children are providing primary care for family members. This
      article aims to alert nurses to the issues involved and highlight the plight of
      these hidden and neglected carers.

PMID- 7580075
TI  - Developing a centre for health information and promotion.
AB  - Following the successful application for nursing development unit funding, the
      children's outpatient department within the Child Health Directorate of the
      University Hospital, Southampton, has developed a number of ambitious plans to
      promote nursing initiatives, one of which was the creation of a centre for health
      information and promotion. This article describes this development.

PMID- 7580077
TI  - Identification of non-infected urine specimens in children.
AB  - The research study reported in this article set out to establish whether reagent
      strip testing of urine specimens could be used to identify non-infected specimens
      accurately, thereby reducing the number of specimens sent for laboratory testing.

PMID- 7580078
TI  - The development of advanced nursing practice: 2.
AB  - The first part of this article discussed the development of the advanced nursing
      practitioner role. In this article the author describes how she interpreted the
      role in an initiative at Evesham Community Hospital by integrating clinical
      practice, management, research and education elements into her nursing role.

PMID- 7580079
TI  - Ethical issues in research.
AB  - There are many ethical issues in relation to research when dealing with human
      subjects, e.g. confidentiality, dignity, benefit-to-risk ratio and informed
      consent. The integrity of researchers is paramount. For nurses, there is
      potential role conflict between the role of researcher and the role of patient's
      advocate. Cultural variations in ethical acceptability complicate the issues in a
      multicultural mix of researchers and human subjects.

PMID- 7580080
TI  - Why I will not vote to change Rule 12.

PMID- 7580081
TI  - Verbal handover reports: what skills are needed?
AB  - Nurses require appropriate knowledge, skills and attitudes in order to give and
      receive verbal handover reports effectively. Reports are important for ensuring
      and maintaning continuity and quality of patient care, complying with legal and
      professional requirements and maintaining high team morale. This article will
      discuss the five main reasons for the importance of handover reports, and
      suggestions for further study will be made.

PMID- 7580082
TI  - Stoma care: is there room to extend our practice?
AB  - Much is written about the scope of nurses' professional practice. This article
      examines the ways in which clinical nurse specialists in stoma care may strive to
      extend their practice without losing sight of their ideals.

PMID- 7580083
TI  - Education and professional development in specialist practice.
AB  - This article explores issues of particular relevance to nurses involved in stoma
      care, including formal additional education and preparation, and continuing
      professional development for those already in practice.

PMID- 7580085
TI  - The continent colonic conduit in the management of severe constipation.
AB  - The continent colonic conduit is an innovative surgical technique which has great
      potential for improving the quality of life of certain patients with severe
      evacuatory problems for whom other treatment methods have failed.

PMID- 7580086
TI  - Pegasus Airwave and Bi-Wave Plus.
AB  - The Pegasus Airwave and the Bi-Wave Plus are examples of alternating-pressure air
      mattress (APAM) systems that are more reliable than the older generation of
      APAMs. The Pegasus Airwave is useful for managing severe pressure sores, as well
      as for preventing sores in 'high-risk' patients. The Bi-Wave Plus is more
      suitable for patients with a 'fairly high risk' of developing sores and some
      patients may find it more comfortable than the Pegasus Airwave.

PMID- 7580084
TI  - Homosexuality: a neglected issue in stoma care.
AB  - Problems of living with an altered body image following stoma surgery have long
      been recognised, but the specific needs of homosexual patients undergoing such
      surgery have been largely disregarded. This article examines the ways in which
      nurses can support their homosexual stoma clients.

PMID- 7580088
TI  - Whistle-blowing: a legal perspective.
AB  - Whistle-blowing needs to be explored from a legal perspective. Nurses who become
      aware of confidential information which they feel is a matter of public concern
      are faced with a legal as well as a moral dilemma as to when and how they may
      'blow the whistle'.

PMID- 7580087
TI  - Is the nursing-midwifery alliance at an end?

PMID- 7580089
TI  - Law series: 13. Children: treatment and examination.

PMID- 7580090
TI  - Treading the boards: nurse executives in the spotlight.

PMID- 7580091
TI  - Why hospital medical record keeping must improve.

PMID- 7580092
TI  - Use of humour in patient care.
AB  - Laughter and humour are an intrinsic part of our daily lives, but do nurses
      recognise the importance of humour in reducing stress and promoting feelings of
      wellbeing for patients and fellow staff members?

PMID- 7580094
TI  - Grief: a cognitive-behavioural perspective.
AB  - Models of grief utilised by nurses remain largely descriptive. This article
      considers a cognitive-behavioural model of grief and applies it to the problems
      of morbid grief. Two case studies illustrate how the model may be used to guide
      interventions.

PMID- 7580093
TI  - Surgical nurse principles of audit and clinical practice.
AB  - Health-care providers and purchasers have been concerned with developing methods
      to assure the quality of the service provided in clinical contexts. Crucial to
      this is the integration of multidisciplinary clinical audit techniques which
      facilitate good practice.

PMID- 7580095
TI  - Health education and safer sex.
AB  - Recent studies (e.g. Klee et al, 1991) of human immunodeficiency virus prevalence
      among drug users indicate that the greatest increase in transmission rates has
      been a result of sexual contact. This article examines safer sex health education
      and the development of a programme of education that aims to confront negative
      attitudes towards condoms.

PMID- 7580096
TI  - A study of the mechanism of butachlor-associated gastric neoplasms in Sprague
      Dawley rats.
AB  - Long term administration of butachlor to Sprague-Dawley rats in a previous
      bioassay, resulted in the induction of gastric neoplasms which occurred only in
      the highest dose group (3000 ppm in the diet), primarily in females and
      specifically in the fundic region. The tumors were a composite of highly
      undifferentiated enterochromaffin-like (ECL) cells and mucus producing cells with
      morphologic characteristics unlike those previously described in the rat stomach.
      Mucosal atrophy of marked intensity was a consistent feature of the gastric
      mucosa in animals from the highest dose group. An additional long term study was
      conducted in female Sprague-Dawley rats at dietary levels of 0, 100, 1000 and
      3000 ppm to explore the mechanism(s) involved in the formation of these
      neoplasms. Cell proliferation was evaluated in both fundic and pyloric regions of
      the stomachs of rats at multiple time periods from 14 days to 26 months. Mucosal
      thickness was determined in the fundic region at the same time intervals as were
      used for cell proliferation studies. Gastric pH and gastric acid production were
      measured after approximately 21 months of exposure. Serum gastrin levels were
      analyzed at 14, 60, and 120 days and at 6, 18 and 20 months. Cholecystokinin
      (CCK)/gastrin receptor binding studies were conducted on samples of four tumors
      and pooled fundic mucosa from five animals in the control group. Cell
      proliferation was increased in both the neck and base regions of the fundic
      mucosa at nearly all time points measured from 14 days to 26 months. The
      magnitude of the changes in the base region were substantially greater than those
      in the neck region. Fundic mucosal thickness was decreased beginning at the 30
      day time point and continued at all intervals, being less than one half that of
      controls at 20 and 26 months. Gastric pH in rats from the highest dose was
      elevated to nearly twice control levels at 21 months. Gastric acid secretion was
      dramatically decreased in animals from the 3000 ppm group and was moderately
      decreased in the 1000 ppm group at 21 months. Hypergastrinemia was observed at
      the 3000 ppm level only, beginning at 120 days with progression to extremely high
      levels by 18 months. CCK/gastrin receptor binding was demonstrated in all tumors
      studied, at levels comparable to or higher than that of the pooled control
      sample. All changes involved only the fundic region, the site of tumor formation.
      Tumors occurred only in animals from the 3000 ppm level, the only level at which
      hypergastrinemia occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7580097
TI  - Lack of influence of diethylstilbestrol on induced pancreatic ductal carcinomas
      in Syrian hamsters.
AB  - Syrian golden hamsters were treated with N-nitrosobis-(2-oxopropyl)amine (BOP)
      and/or diethylstilbestrol (DES) for lifetime. After BOP treatment the hamsters
      developed high incidences of pancreatic neoplasms, but DES failed to show any
      effect on these or other tumours.

PMID- 7580099
TI  - Aberrant craniopharyngeal structures within the neurohypophysis of rats.
AB  - Aberrant craniopharyngeal structures within the neurohypophysis were analyzed in
      17 rats, originating from four different colonies of Sprague-Dawley- and Wistar
      derived strains, which were used for toxicity studies in five different
      laboratories. Males were more frequently affected than females. The incidence of
      these findings, which occurred spontaneously and mainly in aged rats, was very
      low. Predominant features included tubular or acinar glandular structures, rarely
      embedded in a fibrous stroma, and, as a rule, not compressing adjacent tissue. In
      some cases, large cysts filled with colloid-like, amorphous material and cellular
      debris were present. The tubular structures consisted of a rather flat
      epithelium, while the cystic elements were lined by a cuboidal or columnar,
      rarely ciliated epithelium, containing goblet cells, or by a stratified squamous
      epithelium. These structures reacted positively for cytokeratin. Acinar
      structures mimicked salivary glands of the serous or mucinous type. In a few
      cases, small, round or fusiform cells were present. Distribution and predominance
      of the various epithelial structures depended on the strain and colony of rats.
      Considering the ontogenic development of the pituitary gland, the morphological
      aspect of these lesions, their immunoreactivity and former reports on similar
      findings, we concluded that these rats have aberrant craniopharyngeal structures
      within the pars nervosa of the hypophysis, originating from remnants of the oro
      pharyngeal epithelium of the craniopharyngeal duct (RATHKE's pouch). These
      lesions, which occurred in different strains and colonies of laboratory rats,
      represent heterotopias or choristomas, consisting of non-neoplastic growth
      disturbances. Being of a distinctly non-proliferative nature, they should not be
      confused with craniopharyngiomas.

PMID- 7580098
TI  - Diagnostic efficiency of troponin T measurements in rats with experimental
      myocardial cell damage.
AB  - A cardioselective parameter has been available for about 2 years since the
      development by KATUS of an immunoassay for cardiac Troponin T (TnT). The major
      advantages of this TnT assay are its cardiospecificity and its sensitivity. The
      parameters usually determined in toxicity studies in rats to detect alterations
      in the myocardial cells, e.g. aspartate aminotransferase (ASAT), creatinine
      kinase (CK) and lactate dehydrogenase (LDH), are either of low sensitivity in
      this species or give falsely high results as the consequence of stress or
      haemolysis. We therefore investigated in the present study how well Troponin T,
      determined with the ELISA Troponin T from Boehringer Mannheim, can detect
      experimentally induced myocardial lesions in rats. In order to achieve hypoxic
      damage of the cardiomyocytes in these experiments in rats, male Sprague-Dawley
      rats were given two doses of 4 mg/kg isoprenaline each (Aludrin from Boehringer
      Ingelheim, FRG) subcutaneously. The second dose was given 7 h after the start of
      the experiment. Serum samples were analysed for Troponin T (TnT) levels and, for
      comparison, aspartate aminotransferase (ASAT), creatine kinase (CK), and lactate
      dehydrogenase (LDH). Histological examinations of the heart muscle were performed
      24 and 96 h after the first injection. As expected, histological examinations of
      the isoprenaline-treated animals revealed marked myofibrillic degeneration of the
      myocardium 24 h after the first injection. Markedly elevated serum TnT levels (up
      to 7.9 ng/ml) were already evident in these animals after 6 h. TnT values
      decreased with time, but were still statistically significant after 48 h. Of the
      well-established indicators for diagnosing myocardial infarction, only ASAT
      showed transient statistically significant increases over 24 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7580100
TI  - Brain peroxidative and glutathione status after moderate hypoxia in normal weight
      and intra-uterine growth-restricted newborn piglets.
AB  - In order to investigate the pathogenetic factors causing the relatively frequent
      occurrence of brain injury in intrauterine growth-restricted newborns, lipid
      peroxidation products (TBAR), glutathione (GSH, GSSG) and in vitro production of
      reactive oxygen species (chemiluminescence, stimulated lipid peroxidation, H2O2
      formation) were studied in the brain of normal weight (NW) and intra-uterine
      growth-restricted newborn piglets (IUGR) after 1 hour of hypoxia (FiO2 11%) and
      90 min reoxygenation. Cardiocirculatory parameters and catecholamine release into
      the blood were also measured. In the cerebellum, higher GSH content, but also
      higher in vitro production of lucigenin amplified chemiluminescence were found in
      comparison to other brain regions, independent of growth restriction and hypoxia.
      Moderate hypoxia without acidosis and hypercapnia resulted in GSH depletion
      especially in the brain of IUGR, but no changes in GSSG concentrations were
      measured. Though TBAR decreased after hypoxia/reoxygenation, in some brain areas
      of IUGR higher TBAR values were found in comparison to NW. H2O2 formation,
      stimulated lipid peroxidation and lucigenin and luminol amplified
      chemiluminescence in the 9000 x/g supernatant of brain tissue did not reveal
      special response of IUGR to hypoxia/reoxygenation. Hypoxia-induced circulatory
      centralisation due to increased release of catecholamines into the plasma
      prevented oxygen deficiency also in the brain of IUGR. The role of brain
      monoamine metabolism in the production of reactive oxygen species, followed by
      greater GSH depletion and higher in vivo formation of lipid peroxides in IUGR is
      discussed.

PMID- 7580101
TI  - Nephrotoxicity of notexin in experimental mice.
AB  - Notexin, a well known neurotoxin, derived from tiger snake venom, was shown to
      have direct nephrotoxic properties in experimental mice. A single subcutaneous
      dose of 1.38 micrograms/kg body weight of notexin produced renal tubular and
      glomerular damage within 24 hours. Renal damage increased in severity
      proportional to the dose of notexin injected. At a high dose of notexin,
      thrombotic "spherules" were found in glomeruli. These thrombotic spherules have
      not been previously reported to be associated with notexin or snake venoms.

PMID- 7580102
TI  - Alterations of melanin synthesis in human melanoma cells selected in vitro for
      multidrug resistance.
AB  - Previous data showing the correlation of multidrug resistance (MDR) and
      differentiation in tumor cell populations (Melloni et al. 1988; Stavrovskaya et
      al. 1990) suggest that: 1) isolation of MDR cells by cytostatic drugs leads to
      the selection of more differentiated cell variants and 2) in more differentiated
      cell variants the activity of MDR-related P-glycoprotein (Pgp) is more prominent
      than in less differentiated cells. Here we used human melanoma cell line mS and
      two variants selected from mS population: a) MDR variant of mS selected by
      colchicine (mS-0.5) and b) mS-trRAR/2--variant obtained by introduction of
      expressing retinoic acid receptor RAR-alpha cDNA into mS cell. The
      differentiation status, expression of MDR1 gene and Pgp functioning were compared
      in wild-type cells and mS variants. Electron microscopic examination of
      melanosomes showed that the mS-0.5 subline comprised more differentiating cells
      in the population than parental mS cultures and that these cells were at later
      stages of melanogenesis. The increase in the degree of differentiation in mS-0.5
      population coincided with MDR1 gene overexpression, occurrence of Pgp molecules
      on the cell membrane and acceleration of Pgp-mediated Rhodamine 123 (Rh123)
      efflux. mS-trRAR/2, proved to be more differentiated than mS cells. The MDR1 mRNA
      level and Rh123 efflux were not elevated in mS-trRAR/2 cells, however, retinoic
      acid (RA) treatment increased both the degree of differentiation and Rh123 efflux
      in mS-trRAR/2 to a greater extent than in mS cultures. Thus, the data obtained in
      this study are in favor of the suppositions mentioned above. The mechanisms of
      coordinated alterations of differentiation and Pgp activity in MDR cells are
      discussed.

PMID- 7580103
TI  - Local skin reactivity after induction of Shwartzman reaction in rabbits.
AB  - A local Shwartzman response was elicited in rabbits by an intradermal injection
      of the Salmonella typhosa endotoxin lipopolysaccharide (LPS) followed 24 hours
      later by an intravenous challenge injection with zymosan. After the intravenous
      challenge, necrotizing vasculitis developed in the prepared skin sites which was
      characterized by microthrombi, accumulation of neutrophil granulocytes, fibrin
      deposition and extravasation of red blood cells. Evans' blue extravasation into
      the altered tissue was significantly reduced, and histologically, the intensity
      of the Shwartzman reaction in the skin was reduced by pretreatment with
      thalidomide and dexamethasone. The mechanism of reduction of an LPS-induced local
      Shwartzman reaction by thalidomide is discussed.

PMID- 7580105
TI  - Preliminary data from investigations of the in vivo biopersistence of three
      experimental glass fibres of varying chemical composition.
AB  - The durability of three experimental glass fibres (X7753, X7484, and X7779) was
      investigated in vivo. These fibres had in vitro dissolution rates of 600, 150,
      and 2 ng cm-2 hour-1, respectively. Three groups of female Fischer-344 rats were
      intratracheally instilled with a 1.2 mg suspension of one of each of the fibre
      types. All fibres had previously been neutron activated, to produce radioactive
      24Na within the glass, which served as a radiotracer. At 2 days post instillation
      (PI) about 1 x 10(6) glass fibres were within the pulmonary region of the lung.
      Animals were killed at various time points from 2 to 360 days PI. Fibres were
      recovered from the animal lungs by hypochlorite digestion. The retention and
      morphometry of these fibres was investigated, and preliminary results are
      presented. After 360 days in the lung, the number of X7753 and X7484 fibres fell
      respectively to 10% and 50% of those present at 2 days PI. There was no
      detectable reduction in the number of X7779 fibres in the lung over this period.
      Morphometric analyses demonstrated a 53% and 22% reduction in the mean length of
      the X7753 and X7484 fibres, after 360 days in the lung. Reduction in diameter was
      apparent after only 28 days for the these fibre types. No change in the mean size
      of the X7779 fibres was observed during the study. The fibre morphometry data
      suggested that short fibres dissolved at a slower rate than long fibres. In
      general the in vivo fibre retention and morphometry data reflected the measured
      in vitro dissolution rate.

PMID- 7580104
TI  - Asbestos-related diseases and asbestos types used in the former GDR.
AB  - In the period from 1960 to 1990 about 1.4 million tonnes of asbestos were
      imported by the former German Democratic Republic (GDR) and mainly processed into
      asbestos-cement products for the building industry. The production was
      concentrated in the former counties of Magdeburg and Dresden. In the past,
      asbestos was primarily used as insulation and fire prevention material, etc. in
      the large-scale chemical industry. Chrysotile was predominantly imported from the
      former Soviet Union, partly from Canada. Very small amounts of amphiboles came
      from Mozambique, but they were not processed in the counties of Magdeburg and
      Halle. In the German Federal State of Saxony-Anhalt, approx. 600 asbestoses,
      almost 2,700 pleural changes caused by asbestos, 843 asbestos-induced
      mesotheliomas and 787 bronchial and laryngeal carcinomas caused by asbestos were
      recorded in the period from 1960 to 1990. A considerable percentage of the
      mesotheliomas are solely due to exposure to chrysotile asbestos.

PMID- 7580106
TI  - Molecular toxicology endpoints in rodent inhalation studies.
AB  - Although histopathology will continue to be essential for assessing the results
      of rodent inhalation studies, molecular toxicology endpoints are of increasing
      importance, as these techniques often complement and extend histopathological
      examinations. One of the primary uses of molecular toxicology is determining the
      delivered dose of the inhaled material to macromolecules in target tissues.
      During inhalation studies this is most often done by measuring DNA adducts in the
      respiratory tract. DNA adducts may be measured specifically (e.g. using
      monoclonal antibodies or mass spectrometry) or non-specifically (e.g. by using
      the 32P-post-labeling assay). Another major use of molecular toxicology
      techniques is the assessment of cellular and molecular changes in target tissues
      which may precede or be more sensitive than histopathologic alterations. For
      example, rates of cellular DNA synthesis occurring in target tissues may be
      quantified at any time during the study by administering the animals either
      radiolabelled thymidine or the non-radiolabelled thymidine analog
      bromodeoxyuridine (BrdU). Pulmonary changes may be assessed in bronchoalveolar
      lavage fluid using either cellular (e.g. macrophage number, granulocyte number)
      or biochemical (e.g. alkaline phosphatase, lactate dehydrogenase) techniques. The
      potential of the inhaled material to produce genetic alterations may be evaluated
      by examining the chromosomes of pulmonary alveolar macrophages for cytogenetic
      changes. To illustrate the use of these endpoints, an experiment was conducted to
      determine the molecular toxicology of aged and diluted sidestream smoke (a
      surrogate for environmental tobacco smoke) in rodent inhalation studies. The
      endpoints measured were DNA adducts in target and non-target tissue, chromosome
      aberrations in pulmonary alveolar macrophages, and DNA synthesis in the
      epithelial lining of the nasal turbinates.

PMID- 7580107
TI  - Long-term clearance of ceramic fibers from guinea-pig lungs.

PMID- 7580108
TI  - Investigation on the biodurability of chemically different stone wool fibres.
AB  - The biodurability is one of the essential factors for a carcinogenic potential of
      mineral fibres. The in vivo solubility of commercial fibre products can be
      influenced by modifications of the chemical composition. Two types of
      experimental stone wool samples with new chemical composition were compared to a
      commercial stone wool sample. Sized fractions of these samples with median
      lengths of 7.1, 9.3 and 6.7 microns, respectively, and median diameters of 0.76,
      1.02 and 0.63 microns, respectively, were intratracheally instilled into female
      Wistar rats with a single dose of 2 mg in 0.3 ml. 5 animals per group were
      sacrificed after 2 days, 1, 3, 6, 12 and 18 months. After low-temperature ashing
      of the lungs about 1,000 fibres per group and sacrifice date were analysed in SEM
      for length and diameter. The number of fibres in the total lung was calculated.
      An analysis of fibre number of different length and diameter fractions was used
      to estimate whether dissolution, breakage or mechanical clearance is responsible
      for the elimination of fibres from the lung. Results indicate that the breakage
      of fibres with length above 20 microns and the dissolution of fibres was faster
      in the experimental stone wool samples compared to the commercial sample.

PMID- 7580110
TI  - Bromo-deoxyuridine (BRDU) uptake in the lungs of rats inhaling amosite asbestos
      or vitreous fibres at equal airborne fibre concentrations.
AB  - Rats were exposed, by inhalation, to target airborne fibre concentrations of 1000
      f/ml (PCOM fibres by WHO criteria) of a long amosite asbestos sample and a
      vitreous fibre sample; the target was closely attained for both fibre samples.
      The size distributions of the two fibre samples was closely similar. Rats were
      placed in the chambers for 7 hours and then, following a further 16 hours in room
      air, were injected with bromo-deoxyuridine (BRDU). The presence of BRDU-positive
      cells in terminal bronchioles/alveolar ducts was assessed in blocks taken from
      various parts of the left lung, from apex to base. There were significant
      differences in the proliferative responses between animals but there were also
      significant differences between the treatments. Lungs from rats exposed to
      vitreous fibres showed no greater response than the controls, but there was a
      markedly greater proliferative response in the lungs of rats inhaling long
      amosite. There was a decreasing gradient of proliferative response from the apex
      of the lung to the base with all treatments. This could be explained by different
      degrees of deposition in different areas of the lung. Similar amounts of fibre
      accumulated in the lungs of rats exposed to the two fibre types and it is
      unlikely that dissolution could be important over the timescale used here. We
      conclude that, when amosite asbestos deposits in the lungs of rats it stimulates
      a proliferative response and that deposition of an equal number of similar-sized
      vitreous fibres has no effect.

PMID- 7580109
TI  - Phagocytosis and chemotaxis of rat alveolar macrophages after a combined or
      separate exposure to ozone and carbon black.
AB  - Male Wistar rats were treated by ozone or carbon black (CB) alone as well as in
      combination. Intratracheal instillation with various amounts of CB was followed
      either by an acute 7-day or subchronic 2-month ozone exposure (0.5 ppm). Two
      functional parameters were investigated in alveolar macrophages from
      bronchoalveolar lavagates, the phagocytotic capacity and the chemotactic
      migration capability. In the phagocytosis assay, the percentage of phagocytizing
      macrophages decreased significantly in the CB-exposed groups whereas the ozone
      groups remained close to or at the control level after 7 days and 2 months of
      exposure, respectively. The number of ingested particles per macrophage and the
      formation of superoxide anion radicals were not changed after a 7-day exposure to
      ozone compared to the control group but were increased after a 2-month ozone
      exposure. However, a reduction was found in the CB groups. A stimulating effect
      of ozone was observed in the combined groups. Chemotactic migration was generally
      retarded in the CB-treated groups. From the results it can be concluded that
      ozone is able to stimulate the phagocytotic and chemotactic activity of alveolar
      macrophages whereas CB impairs these functions.

PMID- 7580111
TI  - Consequences of long-lasting asbestos-exposure: peripheral blood parameters in
      shipyard workers with and without asbestosis.

PMID- 7580112
TI  - Vascular morphology and angiogenesis in glial tumors.
AB  - Intracranial tumor classification is paralleled by a grading system that
      empirically compares tumor entities with "progression stages" of supratentorial
      gliomas of the adult. This grading system is an integral part of the WHO
      classification. Glioma progression has originally been defined by descriptive
      morphology. In this respect, morphological key features of high-grade gliomas
      (WHO grades III and IV) are microvascular proliferation and the formation of
      tumor necroses. Glioma progression is now more accurately defined on the
      molecular genetic level by a stepwise accumulation of oncogene activation and/or
      tumor suppressor gene inactivation. Angiogenesis occurs during development and
      progression of glial tumors. Pathological vessels are a hallmark of malignant
      glioma and it has therefore been suggested that malignant glioma cells are able
      to induce neovascularization. Despite the exuberant neovascularisation, however,
      vascular supply may not be sufficient for tumor areas with high cell
      proliferation, and necroses may develop. Malignant transformation of blood vessel
      itself is a rare event but may be the underlying mechanism of gliosarcoma
      development. The recently purified vascular endothelial growth factor (VEGF) is
      at present the only mitogen known to selectively act on endothelial cells.
      Growing evidence suggests that VEGF is the key regulator of developmental and
      pathological angiogenesis. In vivo, VEGF mRNA is upregulated in a subpopulation
      of malignant glioma cells adjacent to necroses. Since VEGF is hypoxia-inducible,
      hypoxia may be an important regulator of VEGF mRNA expression and tumor
      angiogenesis in vivo. Two tyrosine kinase receptors for VEGF are expressed in
      vessels which invade the tumor, suggesting that tumor angiogenesis is regulated
      by a paracrine mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580114
TI  - Toward a broad-based antisense technology.

PMID- 7580113
TI  - Identity and pathogenesis of stomach tumors in Sprague-Dawley rats associated
      with the dietary administration of butachlor.
AB  - Macroscopic stomach tumors induced in Sprague-Dawley rats during two chronic
      bioassays with the acetanilide herbicide butachlor at a dietary concentration of
      3000 ppm, were evaluated histologically and immunohistochemically in order to
      determine their identity and pathogenesis. The tumors, which occurred primarily
      in female rats, were a heterogeneous series, including a few consisting wholly or
      partly of classic solid or anaplastic epithelium, but with the majority
      containing diffusely distributed primitive neoplastic cells. The latter had
      either the general appearance of undifferentiated epithelium or presented a more
      "mesenchyme-like" pattern where the cells were epithelioid, blastema-like,
      neuroendocrine-like or sarcoma-like with fascicular disposition. Gastric
      glandular profiles were also present, usually located near the periphery of the
      tumors, but in some cases extending into the diffuse tumor tissue. Most of the
      tumors displayed variable immunohistochemical reactivity for cytokeratin,
      vimentin and neuron-specific enolase but were negative for muscle-specific actin
      or desmin except in the stromal tracts. Detailed examination of all available
      gastric tissue revealed the presence of additional microscopic neoplasms and
      precursor hyperplastic lesions. All of these were typical gastric neuroendocrine
      cell lesions (gastric carcinoids) originating in the fundic mucosa but
      occasionally invading submucosally, and consisting of epithelial cells in
      organized clusters, rosettes or primitive tubules. The enterochromaffin-like
      (ECL) nature of these microscopic neoplasms and precursor lesions was
      substantiated by strong immunohistochemical reactivity for cytokeratin, neuron
      specific enolase and chromogranin A, and a negative reaction for vimentin. One
      microscopic tumor showed a transition from differentiated neuroendocrine type in
      the fundic mucosa to a dispersed "mesenchyme-like" pattern in the submucosal
      extension. An additional finding in the butachlor-treated male and female rats
      was atrophy of the fundic mucosa involving, in particular, reduction in the
      numbers of parietal cells. This effect was dose-related, being most severe in the
      high-dose (3000 ppm) females. On the basis of their morphological
      characteristics, coupled with the continuity evident in the microscopic lesions,
      it is concluded that the macroscopic stomach tumors associated with the dietary
      administration of butachlor are poorly differentiated gastric carcinoids, in some
      cases admixed with a non-neuroendocrine epithelial element. Fundic ECL and stem
      cells are known to be under the trophic influence of gastrin, which is apparently
      responsible for the induction of the tumors associated with butachlor
      administration. Gastric tumor development involving gastrin is recognized as a
      secondary, hormonal mechanism of carcinogenesis, demonstrating a dose-threshold
      phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7580115
TI  - Stability and pharmacokinetic characteristics of oligonucleotides modified at
      terminal linkages in mice.
AB  - To construct the strategy for delivery systems that can control in vivo
      disposition of antisense oligonucleotides, we studied the stability and basic
      pharmacokinetic characteristics of oligonucleotides. Decathymidylic acid (T10), a
      model oligodeoxynucleotide, and its derivatives, 5'-biotin-T10) and 3'
      methoxyethylamine 5'-biotin-T10 (3'M5'B-T10), containing phosphoroamidate
      modification at 3'- and/or 5'-terminal internucleoside linkages, were
      synthesized. In phosphate-buffered saline (PBS, pH 7.4) containing 10% mouse
      serum, unmodified T10 was degraded with a half-life of 45 minutes; the
      degradation half-lives of 5'B-T10 and 3'M5'B-T10 were 11 and 30 h, respectively.
      In mouse whole blood, 3'M5'B-T10 was relatively stable, and 45% remained intact
      after 1 h incubation. After intravenous injection of [3H]3'M5'B-T10 into mice at
      a dose of 1 mg/kg, the radioactivity was rapidly cleared from plasma with a half
      life of 2 minutes and accumulated in the kidney, liver, and gallbladder. About
      30% of the dose was excreted in the urine within 60 minutes. A much more rapid
      degradation of [3H]3'M5'B-T10 was observed in vivo than expected from in vitro
      experiments: more than 90% of the radioactivity in plasma was degradation product
      at 2 minutes after injection. These results suggested that enzymatic degradation
      occurred in some compartments in addition to the blood pool. The apparent urinary
      excretion clearance of [3H]3'M5'B-T10 was close to that of inulin, whereas the
      apparent hepatic uptake clearance was much greater than that of inulin and
      comparable to that of dextran sulfate, which is taken up by the liver by
      scavenger receptors for polyanions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580117
TI  - Characterization of binding sites, extent of binding, and drug interactions of
      oligonucleotides with albumin.
AB  - Phosphorothioate oligonucleotides (S-ODNs) have the ability to modulate gene
      expression selectively and thus have potential therapeutic capabilities. This
      potential led us to investigate the protein binding characteristics of selected S
      ODNs. We evaluated S-ODN interactions with bovine serum albumin (BSA) and human
      serum albumin (HSA) in vitro. The equilibrium dissociation constants Km for the
      binding of a 20 mer S-ODN with BSA and HSA range between 1.1-5.2 x 10(-5) and 2.4
      3.1 x 10(-4) M, respectively. The Km for an unrelated 15 mer S-ODN binding with
      HSA ranges between 3.7 and 4.8 x 10(-5) M. Studies with a fluorescently labeled
      27 mer S-ODN suggest cooperative binding (Hill slope = 1.67) and/or the presence
      of secondary binding sites on the S-ODN. HSA or BSA linked to Sepharose was
      incubated with a 15, 20, or 24 mer S-ODN followed by the addition of selected
      drugs known to be highly protein bound (nifedipine, warfarin, midazolam,
      probenecid, indomethacin, and mitoxantrone). Up to 30% of S-ODN was displaced by
      warfarin in competition binding assays. Conversely, HSA-bound warfarin was
      incubated with a variety of oligonucleotides, including RNA and genomic dsDNA.
      Maximum displacement of warfarin-bound HSA was observed following incubation with
      5'-cholesterol-conjugated 20 mer S-ODN. In summary, S-ODNs are likely to interact
      and displace other therapeutic agents that bind to albumin, particularly those
      binding at site I.

PMID- 7580116
TI  - Uptake, intracellular distribution, and stability of oligodeoxynucleotide
      phosphorothioate by Schistosoma mansoni.
AB  - The in vitro uptake, cellular distribution, efflux, stability, and toxicity
      levels of an oligodeoxynucleotide phosphorothioate (PS-oligonucleotide) have been
      studied in mature Schistosoma mansoni worms. The intracellular accumulation of
      35S-labeled PS-oligonucleotide occurred roughly in proportion to the worm body
      mass over a wide concentration range, whether the worms were exposed singly or in
      mating pairs. Cellular uptake was dependent on the extracellular concentration. A
      minor fraction (13%) of the PS-oligonucleotide taken up by the worm accumulated
      in the surface tegumental coat. Most of the PS-oligonucleotide taken up localized
      in the cytosol (54%) and the nuclei-enriched (33%) fractions. In a time course
      study on adult worms in culture, oligonucleotide uptake was observed within the
      first 2 h and peaked at about 36 h. A decrease in the intracellular concentration
      of the PS-oligonucleotide was observed by 42 h. Analysis of the extracted
      oligonucleotides showed that PS-oligonucleotide was digested slowly. Efflux of
      the oligonucleotide was time and temperature dependent. Significant toxicity to
      the cultured worms did not occur until the PS-oligonucleotide concentration was
      over 8 mg/ml (1 mM).

PMID- 7580118
TI  - Transient expression assay for antisense RNAs using episomal replication of
      plasmids: effective reduction of retinoblastoma gene (Rb-1) product by its
      antisense RNA complementary to 3'-untranslated region.
AB  - We have developed a transient expression assay for selection of effective
      antisense RNAs using episomal replication of plasmids in COS-7 cells, an African
      green monkey kidney-derived cell line expressing SV40 large T antigen. The
      transient expression assay was enabled by a liposome-mediated DNA transfection
      method, by which about 70% of the cells were reproducibly transfected with
      exogenous DNAs. Plasmids expressing antisense RNAs for the retinoblastoma gene
      (Rb-1) mRNA and harboring SV40 ori were constructed and introduced into COS-7
      cells to examine their inhibitory effect on the accumulation of endogenous Rb
      protein (pRb). Only the antisense RNA complementary to the 3'-untranslated region
      (UTR) in Rb-1 mRNA was expressed stably at high levels for 3 days after the
      transfection. This antisense RNA reduced by 73% the content of endogenous pRb 70
      h after transfection. A similar inhibition was detected in mouse mammary
      carcinoma cells (FM3A) that were stably transfected with the antisense RNA
      expressing vector directed to 3'UTR. In contrast, no obvious change in pRb was
      observed with antisense RNAs complementary to the coding region of Rb-1 mRNA. The
      cellular content of these antisense RNAs was lowered by degradation; thus these
      RNAs did not affect the levels of pRb in COS-7 and FM3A cells. These results,
      taken together, suggest that the expression levels and the stability of antisense
      RNAs are involved in their repressive activity, and our transient expression
      assay provides a rapid and easy system for evaluation of ectopic antisense RNA
      activity in COS-7 cells.

PMID- 7580119
TI  - Helix-stabilizing agent, CC-1065, enhances suppression of translation by an
      antisense oligodeoxynucleotide.
AB  - The antitumor antibiotic CC-1065 is known to bind at selected sequences in the
      minor groove of duplex nucleic acids and to hyperstabilize the duplexes against
      thermal melting. These properties suggested that CC-1065 may enhance translation
      inhibition by antisense oligonucleotides directed against a specific mRNA. A 585
      bp mRNA transcript containing the equine infectious anemia virus (EIAV) S2 gene
      and a portion of the env gene was prepared. Also, a complementary 20 mer
      antisense oligodeoxynucleotide (5'-TGTTGGGTAATAGG-GGTTGA-3') was prepared against
      a target sequence in the mRNA located near the translational initiation sites of
      the overlapping S2 and env genes. The center of the target sequence had an
      expected CC-1065 recognition sequence (5'-UAUUA-3'). Translation in the presence
      of CC-1065 and antisense was markedly suppressed compared with that of antisense
      alone. Addition of a sense 20 mer strand, with or without CC-1065, had little or
      no effect on translation. CC-1065 and related compounds may be useful as ligands
      for enhancing the stability of sense-antisense duplexes and for promoting the
      inhibition of translation by antisense oligonucleotides.

PMID- 7580120
TI  - Influence of chromosomal position and copy number of a white-directed ribozyme
      gene on the suppression of eye pigmentation in Drosophila melanogaster.
AB  - Different strains of transgenic Drosophila melanogaster carrying one, two, or
      three copies of a heat-shock promoter 70 (hsp70)-driven catalytic antisense RNA
      gene, directed against the white gene, were investigated for the expression level
      of ribozyme RNA. It was found that the steady-state concentrations of the
      hammerhead ribozyme were proportional to the copy number of the genes and that
      the suppressive effect on eye pigment accumulation was dosage dependent. In a
      further experiment, a D. melanogaster strain, deficient in eye pigmentation
      caused by a deletion of the white gene, was used for P element-mediated germline
      transformation: the transposon used contained the hsp70-driven, white-directed
      ribozyme gene and, on the same DNA, the mini-white gene under its own promoter.
      The spatial coupling of the transcription of ribozyme and target RNA resulted in
      more effective ribozyme-mediated inhibition of eye pigmentation under heat-shock
      conditions. These effects were dependent on the chromosomal integration site of
      the transposon.

PMID- 7580121
TI  - The evolution of ideas concerning the function of the neocortex.

PMID- 7580122
TI  - Brain (A) symmetry in monozygotic twins.
AB  - Origin and ontogenesis of human brain laterality are unknown. Using in vivo
      magnetic resonance morphometry we measured cerebral hemispheric asymmetry of the
      planum temporale, a structural substrate of functional laterality, in pairs of
      monozygotic twins concordant or discordant for handedness. In both groups,
      intraclass (i.e., within twin pair) correlations were low. The right-handers
      showed leftward asymmetry whereas the left-handers lacked asymmetry. The
      discordance for lateralized brain anatomy can be accounted for by ontogenetic
      models assuming twinning of an asymmetrical germ or differential action of
      nongenetic factors within twin pairs in utero. The findings confirm a coupling of
      lateralized structure and function of the human brain. At least in monozygotic
      twins, early epigenetic factors must play a role in anatomofunctional laterality
      development.

PMID- 7580123
TI  - Whisker follicle removal affects somatotopy and innervation of other follicles in
      adult mice.
AB  - The present study shows that in the whisker-to-barrel pathway of adult mice
      surgical removal of three whisker follicles leads to the expansion of the
      functional cortical representation of the whiskers adjacent to the lesion into
      the deprived barrels within 8 months. Concomitant with this enlargement, there is
      an increase in follicular innervation of the corresponding whiskers. This
      reorganization of the peripheral innervation may be important for the observed
      reshaping of cortical somatotopy.

PMID- 7580124
TI  - Cytoarchitectonic definition of prefrontal areas in the normal human cortex: I.
      Remapping of areas 9 and 46 using quantitative criteria.
AB  - The classical cytoarchitectonic maps of human prefrontal areas produced by
      various cartographers in the early part of this century, though similar in gross
      topography, differ from one another in their descriptions of the size, shape, and
      precise location of specific regions within the frontal promontory. The current
      advances in human neurobiology stimulated us to reinvestigate the
      cytoarchitecture of the human prefrontal cortex, beginning with areas 9 and 46,
      to establish a set of objective cytometric criteria for identification of these
      areas. Nisslstained and Gallyas-stained celloidin-embedded sections were prepared
      from the left hemispheres of 17 human subjects 23-73 years old, without history
      of neurological disease. In eight cases, light microscopic observations were
      supplemented by morphometric data collected on a research microscope equipped
      with differential interference contrast optics and interfaced to a TV monitor
      with video mixing equipment and a microcomputer. We used the three-dimensional
      counting method of Williams and Rakic (1988) to measure (1) total cortical and
      relative laminar thickness, (2) neuronal packing density per 0.001 mm3 in
      individual cortical layers, and (3) sizes of neuronal somata in selected cortical
      layers. Light microscopic analysis confirmed that the cortical layers are more
      differentiated in area 46 than in area 9, particularly at the borders of layer
      IV. Layers III and V exhibit clearer sublamination in area 9, while layer IV is
      also somewhat wider in area 46 than in area 9 (9.3% vs 6.4% of cortical
      thickness); the overall thickness of the cortex is the same in both areas.
      Cytometric analysis revealed that layer IV neurons of area 46 are more densely
      packed than those in area 9 (55.38 +/- 7.26 vs 45.80 +/- 4.45 neurons/0.001 mm3),
      as are neurons in the supragranular layers II and III combined (53.51 +/ 6.33 vs
      45.69 +/ 3.81 neurons/0.001 mm3). Finally, neurons in area 46 are more
      homogeneous in size than those in area 9. Differences in myeloarchitecture are
      also evident: each area contains numerous, well-stained radial striae and two
      pronounced bands of horizontal fibers, but in general, area 46 is less myelinated
      than area 9. Objective cytometric methods can clearly distinguish two adjacent
      areas within the human prefrontal lobe. These findings may prove useful in the
      areal parcellation of the human cerebral cortex as well as provide a baseline for
      analysis of pathological changes in neurological and psychiatric disorders such
      as a schizophrenia, Huntington's or Alzheimer's diseases.

PMID- 7580125
TI  - Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II.
      Variability in locations of areas 9 and 46 and relationship to the Talairach
      Coordinate System.
AB  - The human prefrontal cortex can be divided into structurally and functionally
      distinct cytoarchitectonic areas, but the extent of individual variation in the
      position, size, and shape of these areas is unknown. Using criteria described in
      the preceding companion article (Rajkowska and Goldman-Rakic, 1995), as well as
      visual inspection, we have mapped areas 9 and 46 in the frontal lobe of seven
      postmortem human brains, and completely reconstructed these dorsolateral regions
      in five of the seven cases. The lateral reconstructions in these five cases were
      analyzed and superimposed on the lateral view of the Talairach and Tournoux
      (1988) coordinate system in such a way as to render both the variability and the
      regions of overlap for the two prefrontal areas in the five different brains.
      Based on this exercise, we developed a set of conservative Talairach coordinates
      to define area 9 and 46. Area 9 is located on the dorsal, lateral, and
      dorsomedial surfaces of the frontal lobe extending along the middle third of the
      superior frontal gyrus and adjacent portions of the middle frontal gyrus in all
      cases examined. Area 46 lies on the dorsolateral convexity and is either
      partially or completely surrounded by area 9. It is consistently found on one or
      more convolutions of the middle frontal gyrus. The superior border of area 46
      with adjacent cortex is also variable within the middle and superior frontal
      sulci, as is the inferior border within the upper wall of the inferior frontal
      sulcus. The genuine variability in the morphology of the human frontal lobe
      indicated by our findings suggests that the differences among the classical maps
      of Brodmann, von Economo and Koskinas, and Sarkissov and others may have been due
      to normal variation among the brains they analyzed. Such variation may underlie
      individual differences in the visuospatial and cognitive capacities subserved by
      these areas.

PMID- 7580126
TI  - Regional and laminar distribution of cortical neurons projecting to either
      superior or inferior colliculus in the hedgehog tenrec.
AB  - Retrograde tracer substances were injected into either the inferior or the
      superior colliculus in the Madagascan hedgehog tenrec, Echinops telfairi
      (Insectivora), to reveal the laminar and regional distribution of corticotectal
      cells and to correlate the labeled areas with architectural data. The tenrecs,
      taken from our breeding colony, have one of the least differentiated cerebral
      cortices among mammals, and experimental investigations of such brains are
      important for the understanding of the evolution and intrinsic organization of
      the more highly differentiated cerebral cortex in other placental mammals.
      Following injections into the inferior colliculus, cortical neurons were labeled
      bilaterally, with an ipsilateral predominance. Most labeled cells were found in
      the caudolateral hemisphere, area 4 as defined by Rehkamper (1981); some were in
      the somatosensorimotor cortex, as defined in a previous study. The labeled
      neurons in area 4 were located in layers V and VI, forming two bands of cells
      separated from each other by a poorly labeled interspace. A further subdivision
      of this presumed auditory region could not be achieved. This entire area was also
      weakly labeled following tracer injections into the superior colliculus. The
      labeled cells, however, were restricted to layer V of the ipsilateral side. The
      most consistent sites of labeled cells following injections into the superior
      colliculus were found in layer V of the ipsilateral caudomedial hemisphere,
      Rehkamper's caudal area 3, and the transitional zone adjacent to the
      retrosplenial cortex. This area is small in comparison to the entire region that
      was found in this study to project to the superior colliculus. The superior
      colliculus also receives projections from the ipsilateral sensorimotor and
      cingulate cortices. The latter projections are particularly striking in
      comparison to other mammals because they originate from along the entire
      rostrocaudal extent of the cingulate/retrosplenial region.

PMID- 7580128
TI  - Patterns of connectivity in the neocortex of the echidna (Tachyglossus
      aculeatus).
AB  - Patchy connections were traced in the visual and auditory cortex of the echidna
      (Tachyglossus aculeatus). Labeled neurons and clusters of axon collaterals were
      distributed in regular arrays after the application of a small crystal
      (approximately 100-300 microns diameter) of the carbocyanine dye Dil (1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) into the upper
      cortical layers. In general, the anterograde and retrograde labels were in
      register, but whereas the anterograde label was distributed throughout all six
      layers, the retrogradely filled neurons were absent from layer 1 and the highest
      density of labeled cells was in layers 5 and 6. The cells contained within the
      patches were all pyramidal or pyramid-like and contained long spines on their
      dendrites. Therefore, despite their unusual location within the lateral posterior
      cortex, the internal structure of the echidna visual and auditory cortices
      resembled that of eutherian mammals in containing a regular columnar array of
      connections that may represent the corticocortical projections.

PMID- 7580127
TI  - Mechanisms of LTP induction in rat motor cortex in vitro.
AB  - The motor cortex displays remarkable plasticity in response to changes in sensory
      and motor experience; however, the synaptic mechanisms underlying functional
      plasticity are not known. It is believed that synaptic processes that alter the
      strength of neuronal connections, such as long-term potentiation (LTP), are
      mechanisms by which synaptic circuits are modified by experience, resulting in
      functional adaptations. In the present study, we examined the mechanisms of LTP
      of synaptic responses in layers II/III to vertical (stimulation in layers V/VI)
      and horizontal (stimulation in layers II/III) inputs, in slices from rat motor
      cortex. Tetanic stimulation in layers V/VI or II/III induced LTP in 60% of the
      field potentials (n = 20) and in 73% of the intracellularly recorded postsynaptic
      potentials (n = 33). LTP was induced in cells with firing patterns characteristic
      of regular-spiking, fast-spiking, or bursting cells. LTP was expressed, for the
      most part, in kainate/AMPA receptor-mediated responses; however, potentiation of
      NMDA receptor-mediated components was also observed. Induction of LTP was
      prevented when either NMDA receptors or dihydropyridine-sensitive Ca2+ channels
      (DSCCs) were blocked, although blockade of DSCCs was less effective in preventing
      LTP induction. Based on the present data and previous LTP studies, we suggest
      that in many forms of LTP more than one mechanism participates in the induction
      process. The present findings may be relevant to the synaptic mechanisms
      underlying functional plasticity in motor cortex.

PMID- 7580129
TI  - Leslie G. Ungerleider: Cortical Discoverer Award.

PMID- 7580130
TI  - Dr. Attila Gulyas: Cortical Explorer Award.

PMID- 7580131
TI  - Stephen Mark Williams: Cortical Scholar Award.

PMID- 7580132
TI  - Morphogenesis in Dictyostelium: new twists to a not-so-old tale.
AB  - Prespore differentiation requires both cAMP-dependent protein kinase and the
      transcription factor GBF, and for one class of prespore genes the two form part
      of a single pathway. It seems that differentiation-inducing factor, the inducer
      of prestalk cell differentiation, may operate via a calcium signalling pathway,
      and terminal stalk cell differentiation is in part regulated by glycogen synthase
      kinase 3.

PMID- 7580133
TI  - Plant development: pulled up by the roots.
AB  - Recent advances in the study of root development in Arabidopsis have begun to
      yield mechanistic insights into the processes that underpin morphogenesis,
      pattern formation and cell differentiation in plants. The most exciting feature
      of these advances is that, as a consequence of the simple and largely invariant
      cellular architecture of the root, the processes can be studied at a cellular
      level. Nevertheless, it is clear that although the cell lineages of the root are
      relatively invariant, we have no evidence that lineage per se is an important
      regulator of development. Instead, all the evidence indicates that the positional
      regulation of inductive cues is of primary importance. The availability of new
      root mutants is alerting us to the complexity of the contribution of cell size
      and cell expansion to plant development.

PMID- 7580134
TI  - Fate maps of the zebrafish embryo.
AB  - In the past few years, we have seen a surge of interest in the zebrafish as a
      model system for the study of embryonic induction and patterning. This review
      summarizes our current knowledge of the organization of zebrafish fate maps
      during early development. Recent advances have addressed the relationship between
      early cleavage planes and the future dorsal axis, the pattern of cell mixing
      during blastula and gastrula stages, and the morphogenesis of the trunk neural
      keel. In addition, refined fate maps have become available for the embryonic
      shield, the central nervous system, and the heart. In combination with recent
      advances in molecular and genetic manipulations, these fate maps set the stage
      for new, more incisive, experimental approaches.

PMID- 7580135
TI  - Lateral specification of cell fate during vertebrate development.
AB  - Cells within equivalence groups interact via lateral specification to determine
      cell fates during development in Caenorhabditis elegans and other invertebrates.
      Populations of cells within the developing zebrafish have features similar to
      those of invertebrate equivalence groups. In a simple example, two identified
      zebrafish motoneurons behave as an equivalence pair in which one cell adopts a
      primary fate and interactions between the cells assign the other cell to a
      secondary fate. A more complicated situation exists for two initially equivalent
      populations of zebrafish neural crest cells. We consider whether mechanisms
      similar to those involved in fate specification within invertebrate equivalence
      groups also function furing fate specification in vertebrates.

PMID- 7580136
TI  - Determination events in the nervous system of the vertebrate embryo.
AB  - Molecular and functional data suggest that the regionalization of the caudal
      portion of the vertebrate embryonic brain (hindbrain) is set up through a process
      of segmentation. In contrast, the more rostrally located met-mesencephalic domain
      (mid-hindbrain junction) appears to follow a mode of specification that relies on
      long-range inducing and organizing activities originating from the central region
      of the domain. Recent studies addressing this mode of anterior/posterior
      determination point to Wnt-1 as a key player in this process.

PMID- 7580137
TI  - Homeotic genes and diversification of the insect body plan.
AB  - The homeotic genes regulate segmental identity by repressing the formation of or
      influencing the morphology of segmental structures during development. The
      specific roles these genes have played in the generation of insect diversity are
      discussed relative to abdominal limb formation and to the evolution of wings as
      novel repeated structures. Other recent findings discussed suggest possible
      'homeotic' origins for the non-homeotic genes found within the homeotic complexes
      of higher insects.

PMID- 7580138
TI  - Chromatin complexes regulating gene expression in Drosophila.
AB  - Polycomb-group proteins form chromatin complexes at target genes such as Ubx,
      providing a cellular memory of gene activity in early development and determining
      the later activity of the gene. The complexes, whose constituents vary depending
      on site and genomic context, initiate at specific sites, but can extend to
      involve larger chromatin domains. How they persist through cell proliferation and
      how they silence gene activity are still open issues.

PMID- 7580139
TI  - The role of brahma and related proteins in transcription and development.
AB  - The differential transcription of Drosophila homeotic genes is maintained by the
      Polycomb and trithorax groups of regulatory proteins, many of which are thought
      to modulate chromatin structure. During the past year, studies of a trithorax
      group member, brahma, and related yeast and human proteins have suggested that
      they are components of huge complexes that assist DNA-binding regulatory proteins
      to overcome the repressive effects of chromatin on transcription.

PMID- 7580140
TI  - Vertebrate limb development.
AB  - The recent identification of Wnt-7a as a signalling molecule in dorsal/ventral
      patterning means that we now have a known signal for control of each of the three
      limb axes. Fibroblast growth factors can allow proximal/distal patterning and
      Sonic hedgehog gene expression signals anterior/posterior patterning. Networks of
      these signals not only coordinate cell responses, but also mutually maintain each
      other. A positive feedback loop is established which coordinates expression of
      Sonic hedgehog in mesenchyme cells of the polarizing region and Fgf-4 expression
      in overlying apical ridge ectoderm. Wnt-7a expression in dorsal ectoderm also
      influences Sonic hedgehog expression in the polarizing region. Initiation of
      development of a complete limb can be achieved with just one signal, a growth
      factor.

PMID- 7580141
TI  - Fibroblast growth factors in mammalian development.
AB  - Polypeptide growth factors are secreted signalling molecules that function as
      intercellular communicators. Detailed analyses of the expression and function of
      members of the fibroblast growth factor (FGF) family and their recepotors have
      demonstrated that the FGF signalling pathways play essential roles in regulating
      cellular proliferation, differentiation and tissue patterning during vertebrate
      embryogenesis. Recent studies on the molecular basis of human dysmorphic
      syndromes have revealed that aberrant FGF signalling during limb and skeletal
      development can lead to pathogenesis.

PMID- 7580142
TI  - Signalling by hedgehog family proteins in Drosophila and vertebrate development.
AB  - Members of the hedgehog gene family encode a novel class of secreted proteins and
      are expressed in embryonic cells known to possess important signalling activities
      in organisms as diverse as flies and chickens. Proteins of the hedgehog family
      act in these different developmental contexts as both permissive and instructive
      signals. How this signalling activity is transduced is (as yet) poorly
      understood, but recent studies point to the involvement of protein kinase A in
      both Drosophila and vertebrates.

PMID- 7580143
TI  - The role of the notochord and floor plate in inductive interactions.
AB  - Recent studies have uncovered new roles for the notochord and floor plate in
      patterning adjacent cells, elaborating their importance as essential organizers
      of neural and paraxial tissue. The identification of key molecules that mediate
      the ability of notochord and floor plate to induce cells to adopt distinct fates
      has provided a first step in elucidating the mechanisms underlying these events.

PMID- 7580144
TI  - Early decisions in Drosophila eye morphogenesis.
AB  - Recent analyses have shed light on the roles of genes involved in early events of
      eye cell determination and the spatiotemporal control of differentiation within
      the eye field. These genes function at sequential steps in the programming,
      initiation, or progression of differentiation, highlighting an elegant
      orchestration of gene activities to achieve this striking developmental event.
      Progress has been made in the study of the coordination between cell cycle
      control and cell differentiation, as well as in the genetic control of
      morphogenetic movements within the developing eye disc.

PMID- 7580145
TI  - Spatial patterning and information coding in the olfactory system.
AB  - The ability of mammals to discriminate thousands of structurally diverse odorants
      appears to derive from the existence of a multigene family that encodes
      approximately 1000 different odorant receptors. Recent studies have used this
      family to explore how the olfactory system organizes sensory information. These
      studies reveal striking patterns of organization suggesting that incoming sensory
      information is first broadly organized in the nose and is then transformed in the
      olfactory bulb into a stereotyped and highly organized spatial map.

PMID- 7580147
TI  - Pattern formation and developmental mechanisms.

PMID- 7580146
TI  - Vertebrate Hox genes and proliferation: an alternative pathway to homeosis?

PMID- 7580149
TI  - G-protein regulation of ion channels.
AB  - Even though the vast majority of ion channels are regulated by voltage,
      extracellular ligands, phosphorylation, intracellular ions, or a combination of
      these influences, probably only a handful of ion channels are regulated by direct
      interaction with activated G proteins. Although results from electrophysiological
      studies of some channels are consistent with the hypothesis of regulation via
      direct physical interactions with G proteins, strong biochemical evidence for
      such interactions is still lacking. In most cases, such evidence has been
      difficult to obtain because ion channels are present at very low abundances in
      cell membranes, or because the molecular identity of the channel is unknown. The
      recent cloning of members of the inwardly rectifying K+ channel and voltage-gated
      Ca2+ channel families should facilitate the rigorous study of the putative
      interactions between G proteins and ion channels.

PMID- 7580148
TI  - The inward rectifier potassium channel family.
AB  - Recent cloning of a family of genes encoding inwardly rectifying K+ channels has
      provided the opportunity to explain some venerable problems in membrane biology.
      An expanding number of novel inwardly rectifying K+ channel clones has revealed
      multiple channel subfamilies that have specialized roles in cell function. The
      molecular determinants of inward rectification have been largely elucidated with
      the discovery of endogenous polyamines that act as voltage-dependent
      intracellular channel blockers, and with the identification of a critical site in
      the channel that mediates high-affinity block by both polyamines and Mg2+.

PMID- 7580150
TI  - Proteins that interact with the pore-forming subunits of voltage-gated ion
      channels.
AB  - Voltage-gated ion channels are composed of pore-forming subunits, as well as
      auxiliary subunits that modify the functions of these channels. In addition, the
      channels interact with other modulatory proteins in a more transient manner,
      although with significant effects on channel activity. Even though many second
      messenger systems influence the voltage-gated ion channels, only in a few cases
      has clear evidence for direct protein-protein interactions been demonstrated.
      Recent biochemical and genetic studies have helped to elucidate the scope of the
      interactions between these ion channels and various modulatory proteins by
      determining the structures and functions of nonpore-forming subunits.

PMID- 7580151
TI  - Cyclic nucleotide gated channels.
AB  - Recent studies have revealed that cyclic nucleotide gated channels have a variety
      of forms and functions. These channels are now thought to be heteromultimers of
      at least two kinds of subunits and to undergo functional modulation. Ion
      permeation involves at least two ion-binding sites, and recent work on the alpha
      subunit suggests that many structural regions are involved in the control of
      channel gating. The continued use of both molecular and physiological approaches
      promises to further our understanding of how these channels work and how they are
      involved in cellular function.

PMID- 7580152
TI  - Functional properties of intracellular calcium-release channels.
AB  - Two major classes of intracellular calcium-release channels have been identified,
      the ryanodine receptor and the inositol 1,4,5-trisphosphate receptor. These
      channels are the largest ion channels identified to date. Recent studies have
      established that approximately 90% of each of these proteins protrudes into the
      cytoplasm, presumably exposing many regulatory sites on the channel and allowing
      functional interactions with other cytoplasmic proteins. Current work is aimed at
      understanding the molecular mechanisms and cellular roles of these regulatory
      processes.

PMID- 7580153
TI  - Structure and function of glutamate and nicotinic acetylcholine receptors.
AB  - The past year has seen remarkable progress in defining the structure of various
      ligand-gated ion channels. Images of opened and closed nicotinic acetylcholine
      receptors at 9 A resolution have now made it easier to identify the
      conformational changes underlying gating. In addition, recent studies on
      glutamate receptors have led to a radical revision of their postulated
      transmembrane topology: models for agonist-binding and allosteric domains now use
      sites previously thought to lie in cytoplasmic loops. Other areas that are being
      actively pursued include identification of the amino acids lining the ion
      channels, accurate measurements of Ca2+ fluxes, and tests of transmembrane
      topology in kainate receptor subunits.

PMID- 7580154
TI  - The inhibitory glycine receptor: architecture, synaptic localization and
      molecular pathology of a postsynaptic ion-channel complex.
AB  - Significant progress has been made towards the identification of functional
      domains of the inhibitory glycine receptor. Several residues crucial for ligand
      binding, ion-channel properties and stoichiometric subunit assembly have been
      identified. A major recent advance has been the finding that the biogenesis of
      postsynaptic glycine receptor clusters requires the tubulin-binding protein,
      gephyrin. Another area of exciting research has focused on mutations of glycine
      receptor alpha and beta subunit genes, which have been found to be causal for
      different hereditary motor disorders.

PMID- 7580155
TI  - Synaptic plasticity: hippocampal LTP.
AB  - One of the most intensively studied forms of synaptic plasticity is long-term
      potentiation (LTP). The past year has seen further evidence advanced on both
      sides of the presynaptic/postsynaptic locus of expression debate, without an
      obvious path to reconcile the two views. Real progress has been made, however, in
      clarifying the possible role of nitric oxide as a retrograde messenger and the
      cellular location of its synthetic enzyme. Intriguing glimpses of the complex
      involvement of metabotropic glutamate receptors in the induction of LTP have also
      appeared.

PMID- 7580156
TI  - Modulation of inhibitory synapses in the mammalian brain.
AB  - Recent studies have identified new forms of short-term and long-term modulation
      at inhibitory synapses. In cerebellum and hippocampus, a transient inhibition of
      synaptic efficacy has been found to involve a Ca(2+)-dependent retrograde
      messenger. Exciting results from work in the visual cortex suggest that forms of
      both long-term potentiation and long-term depression occur in cortical inhibitory
      synapses.

PMID- 7580157
TI  - Get receptive to metabotropic glutamate receptors.
AB  - Glutamate activates not only ionotropic glutamate receptors, but also G-protein
      coupled receptors, called metabotropic glutamate receptors. Recent studies have
      revealed that these metabotropic receptors share distinctive structural
      properties and that they form a subgroup within the heptahelical receptor family.
      The development of ligands that bind specifically to these receptors has provided
      a means of characterizing the important roles they play in the tuning of fast
      synaptic transmission, including the induction of long-term changes in synaptic
      strength. Their involvement in the control of movement, spatial and olfactory
      memory and nociception has recently been demonstrated.

PMID- 7580158
TI  - Trophic factor response to neuronal stimuli or injury.
AB  - Neurotrophic factors are produced by CNS neurons, and have both paracrine and
      autocrine activities. In nerve cells, expression of neurotrophic factors is
      regulated by physiological afferent activity, which implies that these factors
      play a role in activity-dependent plasticity and survival. Neurotrophic factor
      levels are also altered following injury, which suggests that they play a part in
      the neurodegenerative response and synaptic reorganization as well. Recent
      studies have examined extensively the regulation and functional roles of the
      neurotrophin family, and have also identified other neurotrophic factors present
      in brain that are regulated by different, as well as similar mechanisms.

PMID- 7580159
TI  - Clinical relevance of defects in signalling pathways.
AB  - This review discusses seven diseases of the human nervous system that have been
      linked to defects in signal transduction. Recent molecular genetic analyses of
      rare monogenic disorders have led to the identification of mutant genes in six of
      the seven diseases. The molecules implicated are an enzyme (superoxide dismutase)
      and ion channels gated by either voltage or ligands.

PMID- 7580160
TI  - Calcium regulation of gene expression in neurons: the mode of entry matters.
AB  - Ca2+ entry into neurons is one of the major effectors of stimulus-induced
      physiological change. Ca2+ can enter neurons through a number of different
      voltage-gated and ligand-gated channels. Depending on the route of entry, Ca2+
      stimulates distinct intracellular signaling pathways, which activate different
      sets of genes, resulting in alternative physiological outcomes for the cell.
      These recent results suggest that the specific effect of a single biochemical
      second messenger can vary as a consequence of its route of entry into the cell.

PMID- 7580162
TI  - Molecular biology and physiology at the single-cell level.
AB  - The functional characterization of the many complex proteins expressed in the CNS
      is a daunting task. The development of nucleic acid amplification techniques has
      provided a powerful tool to tackle this challenging enterprise. Recently, these
      techniques have been successfully used to correlate the functional properties of
      various CNS proteins with their specific mRNA expression patterns in the brain.

PMID- 7580161
TI  - Protein phosphorylation in neuronal plasticity and gene expression.
AB  - Protein kinases and phosphatases are intimately involved in several forms of
      synaptic plasticity. They play a critical role in the initiation of long-term
      potentiation and long-term depression, as well as in the induction of genes that
      permit long-term expression of altered synaptic states. Recent findings
      demonstrate a central role for the cAMP signaling pathway in the persistent phase
      of long-term potentiation. Genetic approaches have established that the
      transcription factor CREB is essential for long-term memory.

PMID- 7580163
TI  - Probing dendritic function with patch pipettes.
AB  - Most neurons in the CNS have complex, branching dendritic trees, which receive
      the majority of all synaptic input. As it is difficult to make electrical
      recordings from dendrites because of their small size, most of what is known
      about their electrical properties has been inferred from recordings made at the
      soma. By taking advantage of the higher resolution offered by improved optics, it
      is now possible to make patch-pipette recordings from the dendrites of neurons in
      brain slices under visual control. This new technique promises to provide
      valuable new information concerning dendritic function.

PMID- 7580164
TI  - Signalling mechanisms.

PMID- 7580165
TI  - Psychoanalysis, psychopharmacology, and the influence of neuropsychiatry.

PMID- 7580166
TI  - Electromechanical characteristics of tardive dyskinesia.
AB  - Fifty patients with mild-to-moderate tardive dyskinesia (TD), who were devoid of
      other clinically apparent movement abnormalities, and 70 neurologically normal
      controls were assessed with a battery of instruments developed to measure and
      analyze the hyperkinetic movements of TD directly, objectively, and
      noninvasively. The electro-mechanical features that most consistently
      characterized and differentiated the TD group were a greater variability of all
      movements, increased energy in the 1-2 Hz frequency band in hand and foot
      movements, and a marked increase in movements during distracting tasks. This
      instrumentation promises to be useful in quantitating abnormal involuntary
      movements, in prospectively following individual patients to scan for small
      deviations from an instrument-established baseline, and in examining patients
      with combined movement abnormalities.

PMID- 7580167
TI  - Subcortical hyperintensities on brain magnetic resonance imaging: a comparison of
      normal and bipolar subjects.
AB  - Bipolar disorder has been reported to occur frequently in a number of subcortical
      diseases. This suggests that subcortical structures may be involved in the
      etiology of bipolar disorder in some patients. With the advent of brain magnetic
      resonance imaging (MRI), in vivo visualization of the subcortical white and gray
      matter is now possible, allowing the examination of these structures. The authors
      report a higher occurrence of deep white matter lesions in bipolar patients (44%)
      compared with age-matched controls (6%). The neuroanatomic and clinical
      correlates of these lesions will be discussed, along with their potential
      pathophysiologic significance.

PMID- 7580168
TI  - Psychostimulants in post-stroke depression.
AB  - The hospital charts of 17 patients with post-stroke depression who were treated
      with either dextroamphetamine or methylphenidate during a 5-year period at the
      Massachusetts General Hospital were examined. Eighty-two percent of the patients
      showed improvement after psychostimulant treatment. Forty-seven percent of all
      patients showed marked or moderate improvement in depressive symptoms. The
      authors saw no significant differences in efficacy between the two
      psychostimulants or across the diagnostic categories for depression. Patients
      improved quickly, usually within the first 2 days of treatment. Adverse reactions
      necessitating the termination of psychostimulant treatment occurred in three
      patients. Anorexia was not observed as a side effect of either dextroamphetamine
      or methylphenidate treatment. Psychostimulants appear to be a safe and rapidly
      effective alternative to tricyclic antidepressants in inpatients with post-stroke
      depression.

PMID- 7580169
TI  - The interaction between depressive affective disorder and neuropsychological test
      performance in multiple sclerosis patients.
AB  - Cognitive impairment of mild-to-moderate severity is known to occur among a large
      proportion of patients with multiple sclerosis (MS). Depressive affective
      disturbances are also known to occur commonly among these patients. In order to
      determine the degree of interaction between mood disturbance and cognitive
      impairment, we conducted a test-retest neuropsychological study of 11 MS patients
      with current major depression diagnosed by Research Diagnostic Criteria. Patients
      were tested while depressed and at another point while euthymic. Nine patients
      were assessed first in a depressed state, followed by a reevaluation in the
      euthymic state, and two were assessed first in the euthymic state. The mean time
      interval between assessments was 7 months. When cognitive performance in the
      depressed condition was compared with cognitive performance in the euthymic
      condition, no significant differences were found. There was evidence for a
      pattern of improvement in verbal memory tests that fell short of statistical
      significance. Some language-related cognitive functions actually deteriorated
      during the 6-month course of this study.

PMID- 7580171
TI  - Neuroendocrine responses to methylphenidate and d-amphetamine: applications to
      attention-deficit disorder.
AB  - The authors reviewed the studies of the neuroendocrine secretion of growth
      hormone, prolactin, and cortisol as they relate to attention-deficit
      hyperactivity disorder (ADHD). Studies to date have focused on the hormonal
      responses to the stimulants (amphetamines and methylphenidate) in children and
      adults. The authors discuss the methodologic limitations of current studies, the
      implications of this research for an understanding of the pathophysiology of
      ADHD, as well as the mechanisms of action of the stimulants and the side effect
      of stimulant-related growth suppression. They also suggest directions for future
      research.

PMID- 7580170
TI  - Brain injury and cognitive function in late-onset psychotic depression.
AB  - Fourteen patients who developed a psychotic depression after age 45 were compared
      with 72 non-psychiatrically ill elderly control subjects using neuroimaging and
      neuropsychological (NP) tests. Despite the fact that the patients were not
      studied if they had an obvious dementia or neurological disease, structural brain
      abnormalities were found in approximately two-thirds of patients and in less than
      10% of controls. The most common abnormality, subcortical white matter (WM)
      lesions, was thought to be vascular in etiology. Also, tumor and primary
      degenerative dementia were found more frequently in the patients. Compared to an
      age-, sex-, and education-matched control group, the patients performed more
      poorly on NP tests of frontal lobe, memory, and visual spatial abilities.
      Diagnostic evaluation of the patient with late-onset psychotic depression should
      include computed tomography or magnetic resonance imaging as structural brain
      abnormalities are common in these patients.

PMID- 7580172
TI  - Cerebral magnetic resonance imaging compared in Alzheimer's and multi-infarct
      dementia.
AB  - Cerebral magnetic resonance images (MRI) were compared between two groups, each
      of 25 patients, one with senile dementia of the Alzheimer's type (SDAT) and the
      other with multi-infarct dementia (MID). MRI proved to be clinically useful for
      differentiating SDAT from MID, utilizing a multivariate model of six MRI criteria
      as follows: ventricular-brain ratio, presence of subcortical infarcts, bifrontal
      ventricular ratio, bicaudate ventricular ratio, third ventricular ratio, and
      presence of diffuse periventricular high-intensity white matter lucencies.
      Utilizing all six MRI criteria, classification by discriminant function analysis
      provided 84% correct diagnostic agreement with clinical classification of MID
      patients, 92% for SDAT patients, and 88% for the total cohort of demented
      patients.

PMID- 7580173
TI  - The effects of electroconvulsive shock on dopamine-1 and dopamine-2 receptor
      ligand binding activity in MPTP-treated mice.
AB  - To explore the possible therapeutic use of electric convulsive treatment in
      Parkinson's disease (PD), the authors examined the biochemical effects of
      electroconvulsive shock (ECS) on dopaminergic systems in a rodent model of PD,
      induced with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      MPTP increased dopamine turnover, as indicated by an increase in the ratio of the
      dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid to
      dopamine. [3H]Spiperone binding to the D2 site increased after lesioning of
      striatal dopamine terminals. With ECS alone, no changes were found in monoamine
      levels, brain monoamine oxidase activity, or the D2-labeled sites measured 24
      hours after the last treatment. [3H]SCH-23390 binding to the D1 site increased
      after ECS. In MPTP-treated mice, ECS also increased [3H]SCH-23390 binding to the
      D1 site, whereas [3H]spiperone binding to the D2 site was unchanged compared to
      control or to only ECS-treated animals, and decreased compared to the MPTP
      treated group that did not receive ECS. ECS appears to selectively modify both
      the D1 and D2 sites when given after MPTP, increasing the binding of a D1
      radioligand and decreasing the binding of a D2 radioligand.

PMID- 7580174
TI  - Risk factors for developing atypical (schizophreniform) psychosis following
      stroke.
AB  - Five patients who developed an atypical schizophreniform psychosis following
      right hemisphere stroke are described and compared to five patients matched for
      lesion size and location who did not develop any psychopathology after stroke.
      The patients who developed the schizophreniform illness had a larger frontal horn
      ratio and larger third ventricle ratio on CT head scans than did the comparison
      group. This finding suggests that preexisting subcortical atrophy and a right
      hemisphere lesion location are risk factors for developing schizophreniform
      disorder following stroke.

PMID- 7580175
TI  - Predicting severity of depression in the elderly at six-month follow-up: a
      neuropsychological study.
AB  - The authors conducted psychopathological and neuropsychological assessments on a
      pilot sample of 15 nondemented elderly depressed patients at the outset of
      inpatient treatment and again after 6 months. Pretreatment performance on a test
      of confrontation naming was predictive of severity of depressive symptoms at
      follow-up. These findings tentatively suggest that the naming ability of elderly
      depressed subjects may have prognostic significance.

PMID- 7580177
TI  - Observations on the physostigmine syndrome in patients with Alzheimer's disease.
AB  - The authors present two patients with Alzheimer's disease who each received a
      single intravenous dose of physostigmine. Subjective complaints and mood changes
      were disproportional with objectively verified physiological side effects. Such
      observations may contribute to an understanding of affective disorders and should
      receive more attention in future studies of cholinesterase inhibitors.

PMID- 7580176
TI  - Quantitative magnetic resonance imaging in Rett syndrome.
AB  - Rett syndrome (RS) is a progressive neurological disorder of females,
      characterized by the early onset of autistic behavior, ataxia, and "handwringing"
      movements. The present magnetic resonance imaging study was undertaken with the
      purpose of investigating whether structural brain abnormalities of RS patients
      are similar to those recently reported in autism. The subject population
      consisted of eight patients and an equal number of age- and sex-matched controls.
      Area and shape measurements were taken at selected anatomical levels for the
      following structures: brain hemisphere, corpus callosum, midbrain, pons, lobules
      I-V and VI-VII of the cerebellum, and head of the caudate. Results revealed
      significant differences in area for the whole brain hemisphere (p < 0.05) and in
      both right and left caudate (p < 0.04). These morphological findings are
      different from those recently reported in autism and emphasize the involvement of
      the striatal system in RS.

PMID- 7580178
TI  - Cerebral infarction in neuroleptic malignant syndrome.
AB  - Two young women with no risk factors for cerebrovascular disease developed
      hyperpyrexia, rigidity, and autonomic features while taking neuroleptic agents.
      The first presented with increasing rigidity, profuse diaphoresis and
      dehydration, and a right hemiparesis, and computed tomography (CT) showed a left
      striato-capsular infarction. The second became unresponsive following severe
      hypoxia and was found to have left-sided pyramidal signs three days later.
      Hemoconcentration and hypoxemia predispose to cerebral ischemic injury in the
      neuroleptic malignant syndrome and should be avoided as much as possible.

PMID- 7580179
TI  - Depression and memory in major depressive disorder.
AB  - The relationship between memory function and depression was examined in 23
      patients who met DSM-III criteria for major depression. All patients were
      unmedicated at the time of examination, which included the Wechsler Memory Scale,
      Minnesota Multiphasic Personality Inventory-Depression Scale (MMPI-D), and
      Hamilton Depression Rating Scale (HDRS). Consistent with previous studies, there
      was no relationship between the MMPI-D and any of the Wechsler Memory Scale
      measures. In contrast, poor memory was related to elevated scores on the HDRS.
      These data indicate that depression does influence memory performance. The most
      important implication of this study is the need for the use of appropriate
      measurement instruments in studies of neuropsychological correlates of
      neuropsychiatric disorders.

PMID- 7580180
TI  - Spontaneous remission of post-stroke depression and temporal changes in cortical
      S2-serotonin receptors.
AB  - A patient with post-stroke depression following infarction of the left basal
      ganglia is described. The patient's depression remitted during a 6-week double
      blind treatment trial while receiving placebo medication. Cortical S2-receptor
      binding that was measured using 11C-N methyl spiperone and positron emission
      tomography (PET), increased in the left temporal cortex by more than 25% during
      the treatment trial. The change in serotonin receptor binding and its
      relationship to the improvement in mood observed in this patient are consistent
      with previously published data demonstrating a correlation between serotonin
      receptor binding in the left temporal cortex and severity of symptoms of
      depression.

PMID- 7580181
TI  - Neuropsychiatric decision making: the role of disorder prevalence in diagnostic
      testing.
AB  - Although the performance of medical diagnostic tests is usually described in
      terms of their sensitivity and specificity, these accuracy indices by themselves
      are of little help to clinicians who need to make decisions about patient care.
      Estimating the probability that a patient with a positive or negative test has or
      lacks a disorder requires the clinician to include the pretest probability of the
      disorder in the interpretation of the test result. This article described several
      approaches to the problem of interpreting diagnostic data in actual clinical
      contexts.

PMID- 7580182
TI  - Can schizophrenia be localized?

PMID- 7580183
TI  - Failure at task-specific regional brain activation: new conceptualization of a
      disease entity.
AB  - The current diagnostic system in psychiatry is symptom-based, as described in
      detail in DSM-III-R. In other branches of medicine the logic of diagnosis is
      based on knowledge of the normal function of the organ system affected by
      disease, and direct measures of pathophysiological process play an increasingly
      important role in clinical practice. New understanding of normal brain function
      has opened the way for psychiatry to begin to follow this path and develop a
      brain-based, rather than symptom-based, nosology. Different models of normal
      brain function, however, suggest quite different theoretical and research
      approaches. One way in which these models differ is the degree to which they link
      specific functions (and illnesses) to specific anatomic locations. In a previous
      paper I discussed the value of adopting a model of brain function that includes
      important roles for the processes that integrate multiple brain regions into ever
      changing functional constellations. In this paper I have proposed the existence
      of a disease characterized by abnormality in the general physiological mechanism
      of task-specific regional brain activation. This is not an etiologic diagnosis
      and therefore presents nothing more than a symptom-based diagnosis about the
      cause of the disorder. However, I predict that this diagnosis will define a group
      of patients that is more homogeneous with respect to both clinical course and
      etiology than do the current symptom-based diagnoses to which these patients
      would otherwise be assigned. Furthermore, it may be possible to develop new
      treatments to address this physiological dysfunction.

PMID- 7580184
TI  - Treatment of depression in Parkinson's disease: a meta-analysis.
AB  - Despite a 40% prevalence of depression in idiopathic Parkinson's disease (PD), an
      extensive literature search found only 12 controlled studies of treatment
      efficacy. A meta-analysis of these was performed in pursuit of guidelines for
      pharmacological treatment. Articles were scored on a scale from 0 to 100 on a
      specially adapted list of methodological criteria. Only 4 articles scored more
      than 50 points, and these generally did not use depression rating scales. Thus,
      there are virtually no empirical data on the treatment of depression in PD.
      Further studies are urgently needed, both for the sake of patient care and to
      gain a better understanding of the pathophysiological mechanisms underlying
      depression in PD and the interrelation between depression and cognitive decline.

PMID- 7580185
TI  - Assessment of treatment outcomes in neuropsychiatry: a report from the Committee
      on Research of the American Neuropsychiatric Association.
AB  - The ANPA Committee on Research conducted a survey of its members and those of the
      British Neuropsychiatry Association to determine the extent to which
      neuropsychiatrists employ formal measures of clinical outcome. Results revealed
      that although respondents endorsed the practice of outcome assessment, formal
      diagnostic evaluations and outcome measures were rarely applied consistently to
      the broad range of neuropsychiatric conditions encountered clinically. These
      findings have implications for clinical research and managed care in
      neuropsychiatry and will form the basis for future work by the Committee on
      Research.

PMID- 7580186
TI  - Neuropsychiatric training in American psychiatric residency training programs.
AB  - Psychiatric residency training directors are faced with the daunting challenge of
      incorporating an avalanche of neuroscientific advance into their programs. This
      survey of U.S. psychiatric residency training directors reveals that 1) the
      majority of residency directors consider that neuropsychiatry should fall under
      the purview of psychiatry and 2) many programs fail to provide adequate training
      in the evaluation and treatment of patients with neuropsychiatric disorders
      associated with problems such as developmental disabilities, movement disorders,
      and head injuries. Residency directors cite lack of faculty with subspecialty
      training in neuropsychiatry as the major hurdle to improving resident training in
      this area.

PMID- 7580187
TI  - The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT.
AB  - Relative stimulus intensity above seizure threshold has been shown to affect
      therapeutic outcome with unilateral ECT. The authors sought to explore whether a
      multivariate ictal EEG model would permit ongoing clinical assessment of this
      parameter. Twenty-five depressed subjects were randomized to either barely (T) or
      moderately (2.5T) suprathreshold ECT treatments. Seizures in 2.5T subjects had
      significantly greater ictal spectral amplitude and coherence, greater postictal
      suppression, and shorter latency until ictal slow-wave onset. A multivariate
      logistic regression ictal EEG model distinguished between stimulus intensity
      groups with 90% accuracy. Preliminary evidence suggests a relationship between
      several ictal EEG indices and therapeutic outcome. A multivariate ictal EEG
      algorithm holds promise as a tool for clinical determination of adequate stimulus
      intensity with unilateral ECT.

PMID- 7580188
TI  - Combined clozapine and electroconvulsive therapy for the treatment of drug
      induced psychosis in Parkinson's disease.
AB  - Drug-induced psychosis is a serious late complication of Parkinson's disease (PD)
      that requires aggressive treatment. Recent studies have found clozapine a highly
      effective and ECT a possibly useful intervention. Two cases are presented that
      illustrate a possible treatment role for ECT. The cases demonstrate that ECT has
      significant but short-lived antipsychotic effects when used alone. However,
      patients who do not respond to clozapine monotherapy can be given adjunctive
      treatment with ECT. The combination therapy resulted in abrupt alleviation of
      psychotic symptoms in one of the cases, and maintenance with low-dose clozapine
      allowed for long-term efficacy. On the basis of these findings, a therapeutic
      approach to patients with drug-induced psychosis in PD is suggested.

PMID- 7580189
TI  - A SPECT study of parkinsonism in Alzheimer's disease.
AB  - The authors examined the presence of significant regional cerebral blood flow
      (rCBF) differences between Alzheimer's disease (AD) patients with and without
      extrapyramidal signs (EPS). Nine patients with probable AD and EPS (resting
      tremor or rigidity and bradykinesia) and 9 AD patients without EPS, comparable in
      age, duration of illness, and global cognitive decline, were studied with
      [99mTc]HMPAO SPECT. Patients with AD and EPS showed significantly lower rCBF in
      the superior frontal, superior temporal, and parietal regions of the left
      hemisphere than AD patients without EPS. Rigidity and bradykinesia independently
      accounted for the decreased rCBF in these areas. These findings suggest that the
      presence of EPS in AD may result from dysfunction in specific brain regions.

PMID- 7580190
TI  - Valproate in the treatment of behavioral agitation in elderly patients with
      dementia.
AB  - Ten nursing home patients ages 71 to 94 years with dementia and behavioral
      agitation were treated prospectively with open-label valproate at doses of 375 to
      750 mg/day over periods of time ranging from 4 to 34 weeks. Change in behavioral
      agitation was rated by nursing staff members. Eight (80%) of the 10 patients
      showed a 50% or greater reduction in the frequency of episodes of behavioral
      agitation. Response was maintained in all patients. Side effects were minimal.
      The authors conclude that valproate may be an effective, well tolerated, and safe
      treatment for behavioral agitation in elderly patients with dementia.

PMID- 7580191
TI  - Evidence for a verbal deficit in alexithymia.
AB  - This study examined the relationship between alexithymia and specific domains of
      cognitive function. Fifty-nine neurologically intact combat veterans completed
      the Toronto Alexithymia Scale (TAS), a number of other symptom measures, and
      several neuropsychological tests. Modest but consistent correlations were noted
      between TAS scores and measures of developmental verbal ability. These
      relationships were not observed between the neuropsychological variables and the
      other symptom measures. Results suggest that poorly developed verbal ability may
      relate to the presence of primary alexithymia, irrespective of secondary
      etiologic factors.

PMID- 7580193
TI  - Lack of postmenopausal estrogen replacement therapy and the risk of dementia.
AB  - Estrogen replacement therapy (ERT) and associated risks for ischemic vascular
      dementia (IVD) and dementia of the Alzheimer's type (DAT) among postmenopausal
      women were investigated by determining whether ERT was differently distributed
      among control subjects than among subjects with dementia. Subjects included 93
      with probable DAT, 65 with probable IVD, and 148 normal control subjects. The
      proportion of control subjects on ERT was almost 2:1, and this ratio holds for
      both dementia groups. Logistic regression suggests lack of ERT is associated with
      increased risk for dementia among elderly women. ERT may eventually prove to be a
      useful prophylactic agent for reducing risk of DAT and IVD among postmenopausal
      women.

PMID- 7580192
TI  - Abnormalities of visual spatial attention in HIV infection and the HIV-associated
      dementia complex.
AB  - Covert orienting of visuospatial attention (COVAT) was examined in 88 homosexual
      or bisexual men: 12 with mild HIV-associated dementia complex (ADC), 30
      neurologically intact with AIDS (NI-AIDS), 23 asymptomatic HIV+ (HIV+ASX), and 23
      HIV-negative control subjects. In mild ADC, COVAT was normal for spatial but
      impaired for nonspatial cues; 17% of NI-AIDS and HIV+ASX subjects had similar
      COVAT impairment patterns and also showed cognitive deficits. HIV+ subjects with
      normal COVAT showed normal cognitive performance. Impairment of nonspatial
      attentional processing in the ADC subjects and subgroups of the neurologically
      intact HIV+ subjects may reflect early subcortical dysfunction caused by HIV
      infection. COVAT assessment may be sensitive for detection of early subclinical
      neurological impairment in HIV infection.

PMID- 7580194
TI  - Anosognosia in Alzheimer's disease: a study of associated factors.
AB  - The authors examined the prevalence and correlates of anosognosia in a
      consecutive series of patients with probable Alzheimer's disease (AD). Patients
      were examined with the Anosognosia Questionnaire-Dementia (AQ-D), which showed
      good reliability and validity. On the basis of the AQ-D scores, patients were
      divided into those with anosognosia (n = 21) and those without anosognosia (n =
      52). Patients with anosognosia showed a significantly longer duration of illness,
      more severe cognitive impairments and deficits in activities of daily living, and
      higher mania and pathological laughing scores than AD patients without
      anosognosia. These findings suggest that anosognosia in AD may be part of a
      specific neuropsychiatric syndrome.

PMID- 7580195
TI  - Rapidly progressive frontal-type dementia associated with Lyme disease.
AB  - The authors report a case of fatal neuropsychiatric Lyme disease (LD) that was
      expressed clinically by progressive frontal lobe dementia and pathologically by
      severe subcortical degeneration. Antibiotic treatment resulted in transient
      improvement, but the patient relapsed after the antibiotics were discontinued. LD
      must be considered even in cases with purely psychiatric presentation, and
      prolonged antibiotic therapy may be necessary.

PMID- 7580197
TI  - Mania in Alzheimer's disease.
AB  - A chart review of 134 patients with Alzheimer's disease (AD) showed a 2.2%
      prevalence of mania, lower than previously cited. Of 3 patients with mania, 2 had
      a history of mania before the onset of AD. Prevalence rates and the role of
      Alzheimer's disease in the development of mania are discussed.

PMID- 7580198
TI  - Mesial temporal lobe seizures presenting as anxiety disorders.
AB  - Five patients had brief simple partial seizures that mimicked panic disorder. The
      following features assisted diagnosis: Seizures were briefer and more stereotyped
      than panic attacks; some progressed to typical complex partial seizures; and
      aphasia and dysmnesia occurred during seizures in some patients. Each patient had
      one mesial temporal structural lesion. Routine waking EEG was normal in 2
      patients. Inadequate response to anti-epileptics necessitated partial temporal
      lobectomy in 4 patients, 3 of whom remain seizure free.

PMID- 7580196
TI  - Methylphenidate in the treatment of neurobehavioral slowing associated with
      cancer and cancer treatment.
AB  - Psychostimulants used in the treatment of psychiatric conditions, including
      depression, alleviate some of the observed psychomotor retardation. We describe 3
      patients with impairments of arousal and psychomotor speed secondary to tumor
      related organic brain dysfunction who benefited from stimulant therapy.

PMID- 7580199
TI  - Validity of the Mattis Dementia Rating Scale for detection of cognitive
      impairment in the elderly.
AB  - The validity of the Mattis Dementia Rating Scale (DRS) for detecting
      neuropsychological impairment was evaluated in 22 elderly patients with mild
      cognitive impairment and 48 rigorously screened control subjects. A cutoff score
      was identified that correctly classified 95% of patients and 100% of control
      subjects. Results of this preliminary study suggest that the DRS may prove useful
      in screening for mild cognitive impairment in elderly populations. Further
      validation with a representative elderly sample is needed to establish screening
      value in primary care or community populations.

PMID- 7580201
TI  - The schizophrenia-like psychoses of epilepsy, V: Discussion and conclusions.
      1963.

PMID- 7580200
TI  - Evaluation of the patient with idiopathic mental retardation.

PMID- 7580202
TI  - Results of ECT for a case of depression in Wilson's disease.

PMID- 7580203
TI  - ECT and treatment of multiple sclerosis.

PMID- 7580204
TI  - Mirthless laughter in a case of Creutzfeldt-Jakob disease.

PMID- 7580205
TI  - Encephalitis lethargica.

PMID- 7580217
TI  - Nicotine uses and abuses: from brain probe to public health menace.
AB  - There has been a notable lack of dialogue between neuroscientists, who use
      nicotine in their work as they would any other pharmacological tool, and public
      policy and health researchers, who view nicotine dependence with increasing
      dismay and see the continued use of tobacco products as a modern day scourge.
      This special journal issue attempts to foster communication among nicotine
      researchers working along the continuum from basic to applied science. An
      additional objective is to convey a sense for the special problems and
      opportunities in the study of nicotine and tobacco use that may be of general
      interest to those concerned with substance abuse. The articles that follow
      explore two themes, (1) nicotine as a tool to probe neural activity, and (2)
      tobacco use as a health hazard and societal problem, by examining nicotine from
      pharmacochemical, biobehavioral, and econo-social perspectives. The rationale for
      the integration is that there may be benefits from viewing nicotine in a context
      broader than those dictated by custom and technological specialization.

PMID- 7580219
TI  - Differential effect of chronic nicotine treatment on nicotinic receptor numbers
      in various brain regions of mice.
AB  - Studies of smoking behavior in human twin pairs indicate that genetic factors may
      influence whether people do, or do not, smoke. Because the ability to develop
      tolerance to behavioral and physiological effects of nicotine may regulate
      nicotine intake, studies of potential genetic influences on tolerance development
      were carried out using inbred mouse strains that differ in initial (first dose)
      sensitivity to nicotine. Nicotine-sensitive strains such as the C57BL and DBA
      strains develop tolerance to nicotine following chronic intravenous infusion of
      lower doses of nicotine than are required to elicit tolerance to nicotine in the
      nicotine-resistant strains such as C3H and BUB. Chronic nicotine infusion results
      in a dose-related increase in binding of [3H]-nicotine to brain membranes in all
      strains. Differences in this effect were seen among brain regions as well as
      between the strains. A quantitative autoradiographic analysis of the effects of
      chronic nicotine infusion on DBA/2 mice, which develop marked tolerance to
      nicotine, clearly indicates that nicotine binding is affected to various degrees
      in various brain nuclei. These results are discussed in terms of genetic
      influences on tolerance development.

PMID- 7580220
TI  - Nicotine as a discriminative stimulus: a neurobiobehavioral approach to studying
      central cholinergic mechanisms.
AB  - A major goal of basic nicotine research is to obtain information useful to the
      clinician in determining why and how people become dependent on this substance
      via the use of tobacco products. To accomplish this, the basic scientist must
      first develop an animal model of nicotine action that is parallel to its effects
      in humans. This review describes such a model, based on the ability of nicotine
      to exert discriminative stimulus (DS) control over behavior. The nicotine DS, as
      studied in the rat, mouse, or subhuman primate, appears to provide information
      analogous to human subjective reports concerning the effects of smoking. Findings
      indicate that nicotine is specific and selective in its actions, explaining, in
      part, why tobacco is dependence-producing. The nicotine DS effect is
      stereoselective and appears to be the result of an action at specific central
      nicotinic cholinergic (N-Ch) receptors located in at least two brain areas, the
      hippocampus and midbrain reticular formation. Whether acetylcholine is the
      mediator of nicotine's effects at these receptor sites, as was once thought, has
      yet to be clearly determined. Finally, these N-Ch receptors appear to have a wide
      distribution and may also sit on presynaptic dopamine neurons, helping to explain
      some of nicotine's additional behavioral and/or rewarding effects.

PMID- 7580221
TI  - Dose-related actions of nicotine on behavior and physiology: review and
      implications for replacement therapy for nicotine dependence.

PMID- 7580223
TI  - Stress, smoking, and the cardiovascular system.
AB  - Smoking is the most important preventable risk factor for coronary heart disease.
      Reactivity to psychological stressors is also believed to be cardiopathologic.
      More recently, evidence has been accumulating that these putative risk factors in
      combination may be particularly harmful, both because smoking increases in
      stressful situations and because the cardiovascular effects of smoking combined
      with those of psychological stress may be greater than those of either alone.
      This paper reviews the literature on the cardiovascular effects of smoking and
      psychological stress in the light of epidemiological data and discusses
      mechanisms by which they may contribute to coronary heart disease.

PMID- 7580218
TI  - Sites, mechanisms, and structural characteristics of the brain's nicotine
      receptor.
AB  - Studies are described dealing with the molecular features of nicotine, the
      receptor binding and psychotropic properties of nicotine agonists and
      antagonists, and the neuroanatomical locus of action of nicotine associated with
      its psychotropic action. Bridged analogues of nicotine have been developed to
      define the optimal conformation of the molecule for maximal receptor affinity and
      psychotropic action in rats. With another series of analogues, it was
      demonstrated that contraction of the pyrrolidine ring to a 4-member azetidine
      enhances potency while expansion diminishes it. A major site for nicotine's
      central action is the vestibular cerebellum as demonstrated by kainic acid
      lesioning studies and direct administration of nicotine into this region.
      Included among the antagonists to nicotine was alpha-lobeline, which appeared to
      be a mixed agonist-antagonist.

PMID- 7580224
TI  - Reduction of tobacco health hazards in continuing users: individual behavioral
      and public health approaches.
AB  - For those smokers who will not stop using tobacco, methods are discussed for
      reducing the risks to health of continued tobacco use. Overall, tobacco users are
      encouraged to reduce their exposure to tobacco toxins as much as they can
      tolerate. The boundary model of nicotine regulation implies that it is practical
      to prevent so-called "needless" excesses of nicotine intake. For continuing
      smokers of cigarettes, fewer cigarettes per day and very-low-tar cigarettes are
      encouraged, provided filter-vents are not blocked by the smoker. Better yet would
      be a switch to smoking one or two non-inhaled pipes or cigars each day. Even
      better would be a switch to use of the minimum acceptable amount of smokeless
      tobacco or nicotine-containing gum. Of course, the best course would be
      abstinence from any form of tobacco or nicotine use. Since relatively few tobacco
      users voluntarily engage in substantially less hazardous ways of using tobacco,
      public health measures (e.g., social restrictions, differential taxation, changes
      in package size) may be the most important means of bringing about less hazardous
      tobacco use among continuing users.

PMID- 7580222
TI  - Environmental determinants of the reinforcing effects of nicotine in humans.
AB  - Experimental studies indicate instructions (told received nicotine > told
      received placebo) and drug history (exsmokers > never-smokers) increase the
      degree to which the stimulus effects of nicotine will serve as a reinforcer in
      humans. Cross-study comparisons and correlational data suggest schedule
      (concurrent > single access to nicotine and placebo), duration of exposure
      (longer > shorter exposure), and setting (therapeutic > experimental settings)
      also increase the reinforcing effect of nicotine. Empirical study of when and how
      environmental factors control the reinforcing effects of nicotine is crucial to
      specifying multicausal models of tobacco dependence.

PMID- 7580225
TI  - Implications of a nicotine-free society.
AB  - Cigarette smoking causes more premature deaths than do all of the following
      together: AIDS, cocaine, heroin, alcohol, fire, automobile accidents, homicide,
      and suicide. A society freed of its addiction to nicotine would ultimately
      experience a life expectancy gain comparable to that that would be achieved by
      the elimination of all cancers not caused by tobacco use. In particular, each
      year, the 390,000 individuals who now succumb to tobacco-related deaths instead
      would realize a life expectancy gain of 15 years. The tobacco industry implies
      that the demise of tobacco consumption would wreak havoc with the economy. By
      contrast, some antitobacco activists suggest that the end of tobacco use would
      yield a multibillion dollar fiscal dividend. Each argument is fundamentally
      flawed. The economic impacts of a nicotine-free society would be modest and of
      far less consequence than the principal implication: a significantly enriched
      quality and quantity of life.

PMID- 7580226
TI  - The Drug Avoidance Self-Efficacy Scale.
AB  - Several scales have been developed to measure self-efficacy for addictive
      behaviors but there is no such scale applicable to multiple drug users. The Drug
      Avoidance Self-Efficacy Scale (DASES) was developed to fill this gap. The
      properties of the scale were evaluated using a sample of 373 young multiple-drug
      users 16 to 30 years old presenting for treatment at the Addiction Research
      Foundation. The 16-item scale appeared to be unidimensional. Cronbach's alpha was
      .9140. Construct validity, evaluated on a subset of the sample, was evident in
      significant correlations with concurrent measures of drug use severity and
      differential rates of changes in self-efficacy associated with two types of
      treatment. The DASES appears to be a reliable and valid scale for the measurement
      of self-efficacy in multiple-drug users.

PMID- 7580230
TI  - The relationship of patients' cognitive status and therapists' ratings of
      psychological distress among psychoactive substance users in long-term
      residential treatment.
AB  - Patients in a long-term residential substance abuse treatment program (N = 168)
      were asked to complete the Symptom Checklist-90-Revised (SCL-90-R), a brief
      inventory that measures psychological distress in nine symptom areas. Using the
      Symptom Checklist-90 Analogue (SCL-90 Analogue), which allows raters to assess
      patients along the same dimensions measured by the SCL-90-R, therapists also
      estimated the degree of psychological distress they observed in their patients.
      Significantly larger discrepancies were found between therapists' ratings of
      their patients and patients' ratings of themselves when patients were cognitively
      impaired (N = 57) than when patients did not display these decrements (N = 111).
      Furthermore, these patient-therapist assessment differences were negatively
      related to measures of patients' participation in treatment and length of stay in
      the program. Clinical and research implications of these findings are discussed.

PMID- 7580228
TI  - Problems in the application of the Addiction Severity Index (ASI) in rural
      substance abuse services.
AB  - The aim of this research was to test the utility of the Addiction Severity Index
      (ASI) in a rural community substance abuse outpatient treatment center and to
      predict future alcohol and drug problems based on ASI information. Substance
      abuse counselors used the ASI to assess the problems of 89 adult clients at
      intake, and research staff assessed drug use outcomes 3 months later. There were
      significant improvements between intake and follow-up on the scores on the
      alcohol, drug, legal, and family sections of the ASI. Scores on the alcohol
      abuse, drug abuse, and medical sections of the ASI predicted some of the variance
      (16%) in drug and alcohol use outcomes, but psychiatric, medical, legal, and
      employment problems were not significant predictors. There was some difficulty in
      obtaining adequate reliability in counselors' severity ratings for alcohol
      problems. The relationship of counselors' severity ratings to the more objective
      composite scores varied substantially by subsection of the ASI. The improvements
      in alcohol and drug use indices appeared to be more related to subjective
      appraisals of problems related to use rather than due to changes in drug-using
      behavior. Implications of these findings and recommendations for further research
      using the ASI are discussed.

PMID- 7580229
TI  - Situational analysis of coping in substance-abusing patients.
AB  - A recently revised version of the Situational Competency Test (SCTDR), a tape
      recorded role-play assessment procedure, was used to evaluate situational
      specificity of coping in hospitalized substance-abusing patients (N = 24).
      Responses to six types of high-risk situations were scored according to coping
      method used (active cognitive, active behavioral, avoidance, help-seeking) and
      objective response parameters (latency, duration, specification, compliance).
      Additionally, patterns of past drug use and self-efficacy were evaluated for
      situational variability and association with coping response measures. Findings
      revealed that the situational profiles for each of the four coping methods were
      distinct, and that each coping method was used differentially across high-risk
      situations. Objective scoring dimensions demonstrated patterns of situational
      specificity, for example, subjects' responses in situations involving unpleasant
      emotions were more delayed, shorter, and less specific than in other types of
      high-risk situations. Heavy past drug use and low self-efficacy were
      significantly related to latency in responding. These findings are consistent
      with previous studies in which substance abusers' coping was shown to be at least
      partially dependent on situational parameters.

PMID- 7580232
TI  - Perceptuomotor function of homeless males in alcohol rehabilitation.
AB  - In a sample of 76 alcohol rehabilitation program (ARP) residents, homeless men
      demonstrated significantly poorer perceptuomotor function than nonhomeless men.
      This difference persisted despite similarities in several factors associated with
      neurobehavioral test scores including demographic characteristics; frequency,
      quantity, and duration of alcohol and other substance use; psychosocial factors,
      including motivation and social support; health, including history of head
      trauma; and neurotoxic occupational exposure.

PMID- 7580231
TI  - Social settings and addiction relapse.
AB  - Despite addiction theorists' acknowledgment of the impact of environmental
      factors on relapse, researchers have not adequately investigated these
      influences. Ninety-six substance users provided data regarding their perceived
      risk for relapse, exposure to substances, and involvement in reinforcing
      activities. These three setting attributes were assessed in their home, work, and
      community settings. Reuse was assessed 3 months later. When controlling for
      confounding variables, aspects of the home settings significantly distinguished
      abstainers from reusers; perceived risk for relapse was the strongest predictor
      of reuse. Exposure to substances and involvement in reinforcing activities were
      not robust reuse indicators. The work and community settings were not significant
      determinants of reuse. These findings offer some initial support for the utility
      of examining social settings to better understand addiction relapse and recovery.
      Identification of setting-based relapse determinants provides concrete targets
      for relapse prevention interventions.

PMID- 7580227
TI  - Increased psychological distress in post-partum, cocaine-using mothers.
AB  - This study investigated psychological symptoms, self-reported postpartum by poor,
      primarily African American women who used cocaine during pregnancy. Ninety-nine
      cocaine-using mothers (COC+) were compared to 44 noncocaine-using mothers (COC-)
      on standardized measures of psychological distress and verbal comprehension.
      Mothers were interviewed to determined extent of drug involvement. COC+ mothers
      reported using alcohol, marijuana, and tobacco at two to three times the rate of
      comparison mothers during pregnancy and reported earlier initiation of marijuana
      use. COC+ women were more likely to admit to interpersonal difficulties and to
      report phobic anxiety and paranoid ideational symptoms. The COC+ group was also
      more likely to have clinically elevated scores on subscales indicating feelings
      of personal inadequacy, phobic anxiety, and paranoia. The use of cocaine, in
      combination with either alcohol or marijuana, was the best predictor of
      psychoticism, hostility, and total number of distress symptoms.

PMID- 7580233
TI  - Effect of cigarette smoking on alcohol treatment outcome.
AB  - Although smoking cigarettes and drinking alcohol are highly correlated, little
      research has examined the effects of smoking on alcohol abusers' posttreatment
      functioning. Alcohol abusers (N = 155) were classified on the basis of their
      pretreatment smoking status as: nonsmoker, ex-smoker, low dependent smoker (first
      cigarette of the day > 10 minutes after waking), and high dependent smoker (first
      cigarette of the day < or = 10 minutes after waking). All subjects had received
      brief cognitive-behavioral outpatient treatment for their alcohol problem.
      Subjects who were less dependent on nicotine had fewer drinking days and fewer
      heavy drinking days prior to entering treatment than those who were more
      dependent on nicotine; the two nonsmoking groups had fewer abstinent days than
      the low nicotine-dependent subjects and fewer heavy drinking days than the high
      nicotine-dependent subjects. At the 1-year follow-up, the two smoking groups did
      not differ from each other on the alcohol variables but reported significantly
      more abstinent days than the two nonsmoking groups. Treatment implications are
      discussed.

PMID- 7580236
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 7580235
TI  - Neuromuscular disorders: gene location.

PMID- 7580234
TI  - DSM-III-R alcohol dependence criteria in Russian and American men.
AB  - Data on the alcohol drinking patterns of U.S. and Russian men currently enrolled
      in alcohol treatment programs are described in terms of quantity of alcohol
      consumed, patterns of alcohol use, withdrawal symptoms, and biopsychological
      problems experienced. Using the criterion standards of DSM-III-R to determine
      alcohol dependence diagnoses as measured by the CIDI-SAM, we found that 99% of
      the U.S. and 97% of the Russian sample met DSM-III-R dependence criteria. In
      general, these data offer some validity for use of the DSM-III-R criteria and
      CIDI-SAM to determine alcohol dependence in a Russian sample. Although
      differences in the patterns and symptoms of alcohol use were found, they may be
      reflective of cultural, social, and economic factors, in addition to
      methodological limitations.

PMID- 7580237
TI  - Double trouble: combined myophosphorylase and AMP deaminase deficiency in a child
      homozygous for nonsense mutations at both loci.
AB  - A 2-yr-old boy had congenital hypotonia, limb weakness, exercise intolerance and
      one episode of myoglobinuria. Histochemical and biochemical analysis of muscle
      showed a combined defect of phosphorylase and AMP deaminase. DNA analysis showed
      that the child was homozygous for the mutations commonly found in both McArdle's
      disease and AMP deaminase deficiency. The father was heterozygous for both
      mutations. The mother was heterozygous for the myophosphorylase gene mutation and
      homozygous for the mutation in the AMP deaminase 1 gene.

PMID- 7580239
TI  - Sarcoid myopathy and mitochondrial respiratory chain defects:
      clinicopathological, biochemical and molecular biological analyses.
AB  - We report on a 33-yr-old female patient with myalgia, CK values up to 3500 Ul-1
      and proximal weakness. An initial muscle biopsy showed myositis. One year later
      an enlarged lymph node was investigated and sarcoidosis diagnosed. In a second
      muscle biopsy inflammatory cells and morphological characteristics of
      mitochondrial myopathy were found. Biochemical analyses indicated a 50% reduction
      in complex II activity of the respiratory chain. Due to failure in clinical
      improvement a third muscle biopsy was performed in 1990 where only 19% of normal
      complex II activity was present. Southern blot analysis of the mitochondrial
      genome was normal. Thus for the first time we describe a patient with sarcoid
      myopathy and a complex II deficiency. Our interpretation is that a pre-existing
      complex II defect became clinically relevant because of additional sarcoid
      myopathy.

PMID- 7580238
TI  - Abnormal expression of intermediate filament proteins in X-linked myotubular
      myopathy is not reproduced in vitro.
AB  - Expression patterns of the intermediate filament proteins (IFPs) desmin and
      vimentin, in biopsy material taken from a 1 day old boy with fatal neonatal X
      linked myotubular myopathy (XLMTM) were compared with the expression of these
      proteins in cultured myotubes, from the same patient. Immunohistochemical studies
      revealed the persistence of high levels of desmin in virtually all, and vimentin
      in most, of the myofibres within the patient's biopsy. Analysis of intermediate
      filament expression in differentiating, cultured muscle cells did not reveal
      overt differences between XLMTM cultures and cultures of control muscle. Titin
      distribution patterns indicated a normal process of myofibrillogenesis in XLMTM
      myotubes. We conclude that the failure to properly regulate IFP-expression is not
      intrinsic to XLMTM muscle fibres. The possibility that this failure is due to a
      defective external, possibly neural factor, is discussed.

PMID- 7580240
TI  - Cytochrome c oxidase deficiency presenting as recurrent neonatal myoglobinuria.
AB  - Markedly reduced cytochrome c oxidase (COX) activity was found in cultured skin
      fibroblasts of an infant with recurrent episodes of acute myoglobinuria,
      hypertonia, muscle stiffness and elevated plasma levels of sarcoplasmic enzymes
      (creatine kinase 96950 U/l, normal below 150) since the age of 3 weeks (COX
      activity: 36 nmol/min/mg protein; normal 65-440; COX/succinate cytochrome c
      reductase ratio: 1.4, normal 3.0 +/- 0.4). The expression of the disease in
      cultured fibroblasts allowed us to carry out a prenatal diagnosis during the next
      pregnancy. Hitherto, mitochondrial respiratory chain deficiency has not been
      established as a cause of recurrent myoglobinuria in childhood. Since most cases
      of myoglobinurias remain poorly understood, we suggest giving consideration to
      respiratory chain deficiency in elucidating the origin of unexplained recurrent
      myoglobinuria in childhood, especially when seemingly unrelated symptoms are
      present.

PMID- 7580241
TI  - Lack of mRNA and dystrophin expression in DMD patients three months after
      myoblast transfer.
AB  - We report our experience on myoblast transplantation in three Duchenne muscular
      dystrophy patients. Pure myoblasts (55 x 10(6) per patient) from HLA-matched
      donors, were injected into a tibialis anterior and the controlateral muscle was
      sham injected. Three months after transplantation, biopsies from the injected
      muscles were negative for dystrophin expression by immunocytochemistry. Reverse
      transcriptase-PCR (RT-PCR) failed to amplify any fragments of the deleted
      regions. This result confirms that myoblast transplantation is feasible, although
      the efficacy of this therapeutic approach is poor.

PMID- 7580243
TI  - Clinical phenotype in congenital muscular dystrophy: correlation with expression
      of merosin in skeletal muscle.
AB  - It has recently been shown that merosin, an extracellular matrix protein linked
      to the dystrophin-associated glycoproteins, is deficient in a proportion of
      patients with classical congenital muscular dystrophy (CMD). We have undertaken a
      detailed study of the clinical features and brain imaging in 24 cases of CMD in
      relation to the merosin status. Immunocytochemistry showed that merosin was
      present in 13 cases and markedly deficient in 11. In the merosin-positive cases,
      the maximum motor achievement was independent walking in 11, walking with support
      in one and sitting unsupported in one (currently 18 months old). In contrast,
      none of the merosin-deficient cases achieved independent ambulation. Two achieved
      walking with support, nine standing with support. In addition, nine of the 11
      merosin-deficient cases had a creatine kinase level greater than 2000 whereas
      only one merosin-positive case had this degree of elevation. Magnetic resonance
      imaging of the brain was carried out on 15 of the children. All eight merosin
      positive cases had normal scans whereas all seven of the merosin-deficient cases
      had significant changes in the white matter. This study has demonstrated that
      children with merosin-deficient CMD have a more severe clinical phenotype and
      associated white matter changes on brain imaging.

PMID- 7580242
TI  - New point mutations and deletions of the connexin 32 gene in X-linked Charcot
      Marie-Tooth neuropathy.
AB  - The purpose of this study was the identification of new mutations of the connexin
      32 (CX32) gene in CMTX families. We report six new mutations of the CX32 gene
      including two medium sized (29 and 18 bp) deletions. The clinical phenotype is
      consistent with CMT peripheral neuropathy in all patients. Four families show
      both male and female patients, with more severe symptoms in males. The disease is
      asymptomatic in females in two families. The clinical deficit in CMTX families
      Nos 1, 2 and 4 with missense mutations of the CX32 gene was mild or moderate.
      Severe weakness of the feet and hands was present in CMTX family No. 5 with a G
      insertion and family No. 6 with a 29 bp deletion in the carboxyl terminal region
      of the CX32 gene. Most likely the severe clinical impact in those families was
      related to frame shift and premature termination of the protein.

PMID- 7580245
TI  - Focal myositis: a clinicopathological study.
AB  - Focal myositis is a rare, benign inflammatory condition that may clinically
      simulate a soft tissue sarcoma. It was first described in 1977 and around 30
      cases have been reported to date. We report two further cases on which we have
      performed immunocytochemistry and electron microscopy. Histology of both lesions
      was identical, showing a destructive inflammatory myopathy with evidence of
      regeneration. Stains for micro-organisms were negative and no viral particles
      were seen on electron microscopy. The immunocytochemical profile of our two cases
      differed from that of polymyositis: with a panel of T- and B-cell markers the
      cellular infiltrate was found to be composed of T-lymphocytes and variable
      numbers of macrophages: sub-typing in one case revealed the T-cells to be
      predominantly CD4+ cells. Use of antibodies to MHC class 1 and 2 antigens showed
      occasional positive inflammatory cells only. Clinicopathological correlations and
      the differential diagnosis are discussed.

PMID- 7580248
TI  - 28th ENMC international workshop: mitochondrial diseases.

PMID- 7580244
TI  - Expression of laminin subunits in congenital muscular dystrophy.
AB  - The expression of laminin subunits M, A, B1 and B2 was studied
      immunocytochemically in 25 cases of classical congenital muscular dystrophy
      (CMD), 11 hypotonic infants, 20 cases of a variety of inherited and acquired
      neuromuscular disorders, and 11 controls. Merosin, as indicated by labelling for
      the M chain, was deficient in 12 (48%) of the cases of classical CMD. Seven cases
      had no detectable labelling for the M chain whereas five showed traces, including
      three cousins from the same family. This suggests that very low expression may
      relate to a possible difference in the molecular defect, compared with cases
      completely devoid of the M chain. The A chain was abundant in regenerating fibres
      and in immature fibres expressing fetal myosin. In all merosin-deficient cases
      the A chain was over-expressed but this was not due to immaturity. A secondary
      reduction in sarcolemmal expression of the B1 chain occurred in five merosin
      deficient cases, whilst expression in vascular tissue was normal. B1 was also
      reduced in one merosin-positive case of CMD, suggesting that other subunits may
      be involved in other forms of CMD. No differences in the expression of the B2
      chain were observed in any of the cases studied. No abnormality in laminin
      subunits was found in controls or other neuromuscular disorders.

PMID- 7580249
TI  - Siblings with rigid spine syndrome and nemaline rod myopathy, a unique
      association.

PMID- 7580247
TI  - The limb-girdle muscular dystrophies--proposal for a new nomenclature.

PMID- 7580246
TI  - Effect of voluntary wheel-running exercise on muscles of the mdx mouse.
AB  - The purpose of this study is to determine whether dystrophin-deficient mdx mice
      are more susceptible to muscle injury and functional impairment than normal C57
      mice when allowed to exercise voluntarily on mouse wheels. The mdx mice were
      significantly impaired when compared to controls as shown by functional,
      contractile and morphometric responses. The distance young mdx mice ran was 67
      78% of young C57 mice, while adult mdx mice ran 31-48% of adult controls. After
      exercise the slow, oxidative soleus of young and adult mdx mice exhibited
      hypertrophy with no changes in strength or fatiguability, while the young C57
      mice increased strength and the adults became less fatiguable. In the adult mdx
      mice the fast EDL, which is primarily glycolytic, exhibits slight hypertrophy
      with a loss of strength, while the young exhibit no changes. These results
      indicate that the mdx mouse adapts differently than the C57 mouse to even
      moderate exercise.

PMID- 7580250
TI  - Intergeneric transfer and functional expression of the tomato disease resistance
      gene Pto.
AB  - Plant disease resistance loci have been used successfully in breeding programs to
      transfer traits from resistant germplasm to susceptible plant cultivars. The
      molecular cloning of plant disease resistance genes now permits the transfer of
      such traits across species boundaries by genetic transformation of recipient
      hosts. The tomato disease resistance gene Pto confers resistance to strains of
      the bacterial pathogen Pseudomonas syringae pv tomato expressing the avirulence
      gene avrPto. Transformation of Nicotiana benthamiana with Pto results in specific
      resistance to P. s. pv tabaci strains carrying avrPto. The resistant phenotype is
      manifested by a strong inhibition of bacterial growth and the ability to exhibit
      a hypersensitive response. Resistance cosegregates with the Pto gene in transgene
      selfings and testcrosses. Our results demonstrate the conservation of disease
      resistance functions across genus boundaries and suggest that the utility of host
      specific resistance genes can be extended by intergeneric transfer.

PMID- 7580252
TI  - A novel class of MADS box genes is involved in ovule development in petunia.
AB  - We isolated and characterized two ovule-specific MADS box cDNAs from petunia,
      designated floral binding protein (fbp) genes 7 and 11. The putative protein
      products of these genes have approximately 90% of their overall amino acid
      sequence in common. In situ RNA hybridization experiments revealed that both
      genes are expressed in the center of the developing gynoecium before ovule
      primordia are visible. At later developmental stages, hybridization signals were
      observed only in the ovules, suggesting that these genes are involved in ovule
      formation. To test this hypothesis, we raised transgenic petunia plants in which
      both fbp7 and fbp11 expression was inhibited by cosuppression. In the ovary of
      these transformants, spaghetti-shaped structures developed in positions normally
      occupied by ovules. These abnormal structures morphologically and functionally
      resemble style and stigma tissues. Our results show that these MADS box genes
      belong to a new class of MADS box genes involved in proper ovule development in
      petunia.

PMID- 7580253
TI  - Male and female flowers of the dioecious plant sorrel show different patterns of
      MADS box gene expression.
AB  - Male and female flowers of the dioecious plant sorrel (Rumex acetosa) each
      produce three whorls of developed floral organs: two similar whorls of three
      perianth segments and either six stamens (in the male) or a gynoecium consisting
      of a fertile carpel and two sterile carpels (in the female). In the developing
      male flower, there is no significant proliferation of cells in the center of the
      flower, in the position normally occupied by the carpels of a hermaphrodite
      plant. In the female flower, small stamen primordia are formed. To determine
      whether the organ differences are associated with differences in the expression
      of organ identity genes, cDNA clones representing the putative homologs of B and
      C function MADS box genes were isolated and used in an in situ hybridization
      analysis. The expression of RAD1 and RAD2 (two different DEFICIENS homologs) in
      males and females was confined to the stamen whorl; the lack of expression in the
      second, inner perianth whorl correlated with the sepaloid nature of the inner
      whorl of perianth segments. Expression of RAP1 (a PLENA homolog) occurred in the
      carpel and stamen whorls in very young flower primordia from both males and
      females. However, as soon as the inappropriate set of organs ceased to develop,
      RAP1 expression became undetectable in those organs. The absence of expression of
      RAP1 may be the cause of the arrest in organ development or may be a consequence.

PMID- 7580251
TI  - Arabidopsis TCH4, regulated by hormones and the environment, encodes a xyloglucan
      endotransglycosylase.
AB  - Adaptation of plants to environmental conditions requires that sensing of
      external stimuli be linked to mechanisms of morphogenesis. The Arabidopsis TCH
      (for touch) genes are rapidly upregulated in expression in response to
      environmental stimuli, but a connection between this molecular response and
      developmental alterations has not been established. We identified TCH4 as a
      xyloglucan endotransglycosylase by sequence similarity and enzyme activity.
      Xyloglucan endotransglycosylases most likely modify cell walls, a fundamental
      determinant of plant form. We determined that TCH4 expression is regulated by
      auxin and brassinosteroids, by environmental stimuli, and during development, by
      a 1-kb region. Expression was restricted to expanding tissues and organs that
      undergo cell wall modification. Regulation of genes encoding cell wall-modifying
      enzymes, such as TCH4, may underlie plant morphogenetic responses to the
      environment.

PMID- 7580255
TI  - Conservation of floral homeotic gene function between Arabidopsis and
      antirrhinum.
AB  - Several homeotic genes controlling floral development have been isolated in both
      Antirrhinum and Arabidopsis. Based on the similarities in sequence and in the
      phenotypes elicited by mutations in some of these genes, it has been proposed
      that the regulatory hierarchy controlling floral development is comparable in
      these two species. We have performed a direct experimental test of this
      hypothesis by introducing a chimeric Antirrhinum Deficiens (DefA)/Arabidopsis
      APETALA3 (AP3) gene, under the control of the Arabidopsis AP3 promoter, into
      Arabidopsis. We demonstrated that this transgene is sufficient to partially
      complement severe mutations at the AP3 locus. In combination with a weak ap3
      mutation, this transgene is capable of completely rescuing the mutant phenotype
      to a fully functional wild-type flower. These observations indicate that despite
      differences in DNA sequence and expression, DefA coding sequences can compensate
      for the loss of AP3 gene function. We discuss the implications of these results
      for the evolution of homeotic gene function in flowering plants.

PMID- 7580254
TI  - Composite structure of auxin response elements.
AB  - The auxin-responsive soybean GH3 gene promoter is composed of multiple auxin
      response elements (AuxREs), and each AuxRE contributes incrementally to the
      strong auxin inducibility to the promoter. Two independent AuxREs of 25 bp (D1)
      and 32 bp (D4) contain the sequence TGTCTC. Results presented here show that the
      TGTCTC element in D1 and D4 is required but not sufficient for auxin inducibility
      in carrot protoplast transient expression assays. Additional nucleotides upstream
      of TGTCTC are also required for auxin inducibility. These upstream sequences
      showed constitutive activity and no auxin inducibility when part or all of the
      TGTCTC element was mutated or deleted. In D1, the constitutive element overlaps
      the 5' portion of TGTCTC; in D4, the constitutive element is separated from
      TGTCTC. An 11-bp element in D1, CCTCGTGTCTC, conferred auxin inducibility to a
      minimal cauliflower mosaic virus 35S promoter in transgenic tobacco seedlings as
      well as in carrot protoplasts (i.e., transient expression assays). Both
      constitutive elements bound specifically to plant nuclear proteins, and the
      constitutive element in D1 bound to a recombinant soybean basic leucine zipper
      transcription factor with G-box specificity. To demonstrate further the composite
      nature of AuxREs and the ability of the TGTCTC element to confer auxin
      inducibility, we created a novel AuxRE by placing a yeast GAL4 DNA binding site
      adjacent to the TGTCTC element. Expression of a GAL4-c-Rel transactivator in the
      presence of this novel AuxRE resulted in auxin-inducible expression. Our results
      indicate that at least some AuxREs have a composite structure consisting of a
      constitutive element adjacent to a conserved TGTCTC element that confers auxin
      inducibility.

PMID- 7580256
TI  - C-terminal deletion analysis of plant plasma membrane H(+)-ATPase: yeast as a
      model system for solute transport across the plant plasma membrane.
AB  - The plasma membrane proton pump (H(+)-ATPase) energizes solute uptake by
      secondary transporters. Wild-type Arabidopsis plasma membrane H(+)-ATPase (AHA2)
      and truncated H(+)-ATPase lacking 38, 51, 61, 66, 77, 92, 96, and 104 C-terminal
      amino acids were produced in yeast. All AHA2 species were correctly targeted to
      the yeast plasma membrane and, in addition, accumulated in internal membranes.
      Removal of 38 C-terminal residues from AHA2 produced a high-affinity state of
      plant H(+)-ATPase with a low Km value (0.1 mM) for ATP. Removal of an additional
      12 amino acids from the C terminus resulted in a significant increase in
      molecular activity of the enzyme. There was a close correlation between molecular
      activity of the various plant H(+)-ATPase species and their ability to complement
      mutants of the endogenous yeast plasma membrane H(+)-ATPase (pma1). This
      correlation demonstrates that, at least in this heterologous host, activation of
      H(+)-ATPase is a prerequisite for proper energization of the plasma membrane.

PMID- 7580257
TI  - Matrix attachment regions and transcribed sequences within a long chromosomal
      continuum containing maize Adh1.
AB  - We provide evidence for the location of matrix attachment sites along a
      contiguous region of 280 kb on maize chromosome 1. We define nine potential loops
      that vary in length from 6 kb to > 75 kb. The distribution of the different
      classes of DNA within this continuum with respect to the predicted structural
      loops reveals an interesting correlation: the long stretches of mixed classes of
      highly repetitive DNAs are often segregated into topologically sequestered units,
      whereas low-copy-number DNAs (including the alcohol dehydrogenase1 [adh1] gene)
      are positioned in separate loops. Contrary to expectations, several classes of
      highly repeated elements with representatives in this region were found to be
      transcribed, and some of these exhibited tissue-specific patterns of expression.

PMID- 7580258
TI  - TATA box and initiator functions in the accurate transcription of a plant minimal
      promoter in vitro.
AB  - The functional architecture of the proximal region of a rice phenylalanine
      ammonia-lyase (PAL) promoter was analyzed by transcription of PAL-beta
      glucuronidase (GUS) templates by whole-cell extracts of rice cell suspension
      cultures. The promoter 5' truncated to position -35 was sufficient for accurate
      initiation of basal transcription. Substitution of the TATTTAA sequence between
      positions -35 and -28 with GCGGGTT or 2-bp substitutions to give TCGTTAA and
      TATGGAA inactivated the minimal promoter. Moreover, the function of the TATTTAA
      sequence was dependent on its position relative to the initiation site; hence,
      this element is an authentic TATA box essential for RNA polymerase II-dependent
      transcription. Substitutions in the TCCAAG initiator cis element (-3 to +3) at
      the -1 (C to A or G) and +1 (A to C or T) residues caused inaccurate initiation,
      whereas mutations at the other residues of this conserved element or sequence
      substitutions between the TATA box and initiator had little effect. TATA box and
      initiator functions were confirmed by analysis of the effects of promoter
      mutations on expression in stably transformed rice cell suspensions and plants.
      We concluded that the proximal region of the PAL promoter has a simple functional
      architecture involving a TATA box appropriately positioned upstream of the
      initiator. Transcription of derivatives of such minimal promoters by highly
      active cell extracts should allow molecular analysis of functional interactions
      between specific cis elements and cognate trans factors.

PMID- 7580261
TI  - Chernobyl and thyroid.

PMID- 7580260
TI  - Analysis of the role of 5' and 3' flanking sequence elements upon in vivo
      expression of the plant tRNATrp genes.
AB  - We have isolated the majority (seven) of the tRNA(Trp) genes of Arabidopsis and
      have studied the 5' and 3' flanking sequence requirements for their efficient
      expression in vivo by using an assay requiring translational suppression of the
      luciferase reporter gene. The expressed tRNA(Trp) genes contain no highly
      conserved 5' flanking sequences; however, these sequences are distinctly AT rich,
      contain several possible TATA elements, and are bound in vitro by recombinant
      plant TATA binding protein. Replacement of the natural 5' flanking sequences with
      three different sequences lacking TATA elements reduced expression in vivo up to
      10-fold; the same effect was observed when the TATA elements of the natural 5'
      sequences were inactivated by point mutations. Introduction of a single TATA
      element from the adenovirus major late promoter into an artificial 5' flanking
      region of the tRNA(Trp) gene enhanced expression in vivo when the TATA element
      was placed at position -32 relative to the first nucleotide of the mature tRNA
      sequence, but not when it was placed at position -24. Primer extension analyses
      of in vitro transcripts revealed that the position of the TATA element helps
      dictate the start site of transcription. Efficient expression of the tRNA genes
      in vivo also required 3' flanking sequences capable of terminating transcription.

PMID- 7580262
TI  - Human follicular and papillary thyroid carcinoma cells interact differently with
      human venous endothelial cells.
AB  - Follicular thyroid carcinomas (FTC) characteristically spread via blood vessels,
      while papillary thyroid carcinomas (PTC) predominantly metastasize to lymph
      nodes. This different behavior of cancer cells originating from one organ was
      investigated by layering multicellular tumor spheroids (MCTS) consisting of
      various kinds of human thyroid cells onto confluent monolayers of human venous
      endothelial cells (HEC). The MCTS and HEC were cocultured in an incubation
      chamber fixed under a microscope, and the behavior of the cells was investigated.
      In this way significant differences between FTC, PTC, and follicular adenoma
      cells (FTA) were observed regarding their in vitro behavior upon interaction with
      HEC. FTC cells required 20 min for adhesion and another hour until they migrated
      out of a spheroid, whereas PTC- and FTA-MCTS were adhesive after 2 h or later,
      and their cells did not start migration until 5 h of incubation. Furthermore, one
      FTC-spheroid triggered about 100 endothelial cells to enter the replication
      cycle, while no spheroid consisting of either PTC or FTA cells induced more than
      20 endothelial cells to start proliferation. During these processes, the cells of
      the MCTS and the endothelial cells contacted each other directly and remained
      viable. The results show that FTC cells interact faster and more intensively with
      human endothelial cells than PTC and FTA cells. Thus the study suggests that an
      enhanced capability of the FTC cells to interact with venous endothelial cells
      might favor the clinically observed hematogenous spreading of follicular thyroid
      carcinomas.

PMID- 7580263
TI  - Assessment of the influence of thyroglobulin (Tg) autoantibodies and other
      interfering factors on the use of serum Tg as tumor marker in differentiated
      thyroid carcinoma.
AB  - The purpose of the study was to examine the value of a commercial
      immunoradiometric (IRMA) method for measuring serum thyroglobulin as a tumor
      marker after treatment for differentiated thyroid carcinoma. A prospective
      analysis of consecutive serum samples from 53 patients was performed using the
      IRMA method and a traditional double antibody radioimmunoassay (RIA). The results
      were compared with those of 100 healthy control subjects and furthermore the
      method was validated by investigating sera from 24 patients with Hashimoto's
      thyroiditis positive for thyroglobulin autoantibodies. Finally, in vitro studies
      of the influence of thyroglobulin autoantibodies on the method were done. The
      IRMA method had an acceptable analytical precision and was more sensitive than
      the RIA. It was furthermore less sensitive to the presence of thyroglobulin
      autoantibodies but it was affected by them, and it showed less unspecific serum
      effect. Both methods had limitations as tumor marker when the patients had a
      thyroid remnant, when serum thyrotropin was not suppressed, and in cases of local
      recurrence. The highest predictive value was found in patients with distant
      metastases. Thus, in cases of only slightly elevated serum thyroglobulin, the
      strongest indication for recurrence is still an increasing serum thyroglobulin
      level within the same patient rather than a single value.

PMID- 7580265
TI  - Nongoitrous (type I) amiodarone-associated thyrotoxicosis: evidence of follicular
      disruption in vitro and in vivo.
AB  - Treatment with the antiarrhythmic agent amiodarone results in alterations in
      thyroid hormone metabolism, and can induce either hypothyroidism or
      hyperthyroidism (amiodarone-associated thyrotoxicosis, AAT). AAT occurs in
      patients both with and without preexisting goiter. In our study of the
      nongoitrous variety, the effect in vitro of amiodarone treatment and of
      concurrent treatment with potential inhibitors on thyroid cells (FRTL-5) was
      assessed by measuring the release of radiolabeled chromium (51Cr). In addition,
      thyroid histopathology was evaluated in autopsy specimens from six amiodarone
      treated patients who had no pretreatment evidence of thyroid disease.
      Histopathologic examination revealed minimal or no evidence of thyroid follicular
      damage in specimens from amiodarone-treated euthyroid patients (n = 4). In
      contrast, moderate to severe follicular damage and disruption were present in
      glands from patients with AAT (n = 2). Studies in vitro showed amiodarone to be
      cytotoxic to thyroid cells; this effect was inhibited by treatment with
      dexamethasone (10(-3) mmol) or perchlorate (2.5 micrograms/mL). In summary, we
      demonstrate evidence in vitro and in vivo of amiodarone-induced thyroid
      follicular damage and disruption in specimens from patients with nongoitrous AAT
      and in cultured normal thyroid cells. In addition, we demonstrate inhibition of
      this effect following treatment in vitro with dexamethasone or perchlorate. Our
      findings support the concept that nongoitrous (type I) AAT results from direct
      drug toxicity with disruption of thyroid follicles and subsequent release of
      preformed thyroid hormone.

PMID- 7580259
TI  - The stroma of higher plant plastids contain ClpP and ClpC, functional homologs of
      Escherichia coli ClpP and ClpA: an archetypal two-component ATP-dependent
      protease.
AB  - A cDNA representing the plastid-encoded homolog of the prokaryotic ATP-dependent
      protease ClpP was amplified by reverse transcription-polymerase chain reaction,
      cloned, and sequenced. ClpP and a previously isolated cDNA designated ClpC,
      encoding an ATPase related to proteins encoded by the ClpA/B gene family, were
      expressed in Escherichia coli. Antibodies directed against these recombinant
      proteins recognized proteins in a wide variety of organisms. N-terminal analysis
      of the Clp protein isolated from crude leaf extracts showed that the N-terminal
      methionine is absent from ClpP and that the transit peptide is cleaved from ClpC.
      A combination of chloroplast subfractionation and immunolocalization showed that
      in Arabidopsis, ClpP and ClpC localize to the stroma of the plastid. Immunoblot
      analyses indicated that ClpP and ClpC are constitutively expressed in all tissues
      of Arabidopsis at levels equivalent to those of E. coli ClpP and ClpA. ClpP,
      immunopurified from tobacco extracts, hydrolyzed N-succinyl-Leu-Tyr
      amidomethylcoumarin, a substrate of E. coli ClpP. Purified recombinant ClpC
      facilitated the degradation of 3H-methylcasein by E. coli ClpP in an ATP
      dependent fashion. This demonstrates that ClpC is a functional homolog of E. coli
      ClpA and not of ClpB or ClpX. These data represent the only in vitro
      demonstration of the activity of a specific ATP-dependent chloroplast protease
      reported to date.

PMID- 7580264
TI  - Specific effects of radioiodine treatment on TSAb and TBAb levels in patients
      with Graves' disease.
AB  - Radioactive iodine (RAI)-induced changes in the levels of antibodies to the
      thyroid-stimulating hormone (TSH) receptor (TRAb) in patients undergoing
      treatment for autoimmune thyroid disease have been well documented. Previous
      studies have reported effects on the overall level of the antibodies present, TSH
      binding inhibitory immunoglobulins (TBII), without detailed studies of specific
      effects on the levels of thyroid-stimulating (TSAb) or thyroid-blocking
      antibodies (TBAb). More detailed studies have been reported only in individual
      cases. In this study, the values of TSAb, TBAb, and TBII were measured
      longitudinally in 33 patients (27 females and 6 males) who received RAI. The
      bioassays for TSAb and TBAb were performed in JPO9 cells. Following RAI, there
      were significant and immediate effects on the values of TBII in 70% of patients.
      TBII levels fell in 7 patients (20%) (Group 1), rose in 16 patients (48%) (Group
      2) or remained unchanged but elevated in 10 patients (32%) (Group 3). In the
      Group 1 patients, only TSAb were detectable and none of these patients became
      hypothyroid after treatment. In the 16 patients in Group 2, increases in TBII
      were attributable to specific increases in TSAb in 7 (44%), in TBAb in 3 (19%),
      and in both TSAb and TBAb in 3 (19%). There were 3 patients (19%) in this group
      in whom there was no detectable TSAb or TBAb activity despite the increase in
      TBII. Six patients from this group became hypothyroid within 6 months of RAI
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580266
TI  - MR T2 relaxation time for the assessment of retrobulbar inflammation in Graves'
      ophthalmopathy.
AB  - The results of 39 patients with severe Graves' ophthalmopathy (GO), who were
      monitored by magnetic resonance imaging (MRI) and tonography before and after
      combined immunosuppressive treatment with cyclosporine and corticosteroids, are
      presented. A correlation was found between the decrease in T2 relaxation time of
      the superior, medial, and inferior rectus muscle (p < 0.01) and the response to
      the immunosuppressive treatment. Muscle thickness and intraocular pressure showed
      less improvement (p < 0.05). The infiltrative eye signs improved partially in
      correlation with the T2 relaxation time. By distinguishing inflammation of the
      extraorbital muscles from fibrosis, the T2 relaxation time can help to select
      patients that benefit from immunosuppressive treatment as well as to monitor the
      therapeutic effect.

PMID- 7580268
TI  - Subclinical hypothyroidism does not lead to alterations either in peripheral
      nerves or in brainstem auditory evoked potentials (BAEPs).
AB  - Functional alterations in the central nervous system and peripheral nerves are
      well documented in overt hypothyroidism, but not in subclinical hypothyroidism.
      Twenty-seven patients with subclinical hypothyroidism were compared with a
      control group of 20 age- and sex-matched subjects to determine whether
      subclinical hypothyroidism can lead to alterations in peripheral nerves or in the
      brainstem auditory evoked potentials (BAEPs). None of the patients had carpal
      tunnel syndrome or any other neurological or metabolic disturbances. Disease
      duration (expressed as the time from diagnosis of subclinical hypothyroidism to
      the time of neurological testing) ranged from less than 1 month to 6 months
      (median 2.5 months). We studied the distal motor latency, nerve conduction
      velocity (NCV), compound muscle action potentials, and F response in the median
      and peroneal nerves whereas the sensory nerve conduction velocity and sensory
      potential amplitude were measured in the sural and median nerves.
      Electrophysiological parameters and interpeak latencies yielded no significant
      difference between patient and control groups. The present study indicates that
      subclinical hypothyroidism of short duration does not lead to abnormalities of
      peripheral nerves or brainstem auditory evoked potentials.

PMID- 7580269
TI  - Screening for PIT1 abnormality by PCR direct sequencing method.
AB  - PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene, which
      encodes a pituitary specific transcription factor Pit-1/GHF-1.PIT1 abnormality
      has been reported in several patients displaying either complete or incomplete
      deficiency of thyrotropin (TSH), growth hormone (GH), and prolactin (PRL) in
      either familial or sporadic cases. To see if there are abnormalities in the PIT1
      gene in patients with incomplete TSH, GH, and PRL deficiency, we utilized a PCR
      direct sequencing method to determine the Pit-1/GHF-1 coding sequence. A total of
      15 patients, 1 patient from a family with TSH and GH deficiency, 3 patients with
      TSH, GH, and PRL deficiency, and 11 patients treated with both human GH (hGH) and
      thyroid hormone were studied. In one patient of combined pituitary hormone
      deficiency, the Arg-271-Trp mutation was detected. Since both of the parents did
      not harbor this mutation, it is a de novo germ line mutation. No mutation was
      detected in the other patients, showing that PIT1 abnormality is not a frequent
      cause of GH deficiency.

PMID- 7580267
TI  - New assays for the measurement of serum antibodies reactive with eye muscle
      membrane antigens confirm their significance in thyroid-associated
      ophthalmopathy.
AB  - Although sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (SDS
      PAGE) and Western blotting are widely used to detect serum antibodies in patients
      with autoimmune disorders, this procedure unfolds and denatures proteins and may
      alter antibody binding sites. We have used nondenaturing methods for the
      purification of a 64-kDa eye muscle (EM) membrane antigen associated with thyroid
      associated ophthalmopathy (TAO). Pig EM membrane proteins were prepared from
      crude homogenates by high-speed centrifugation and solubilized by hand
      homogenization. The 64-kDa protein was further purified by isoelectric focusing
      performed in the absence of SDS, detergents, reducing agents, and urea. Sera from
      patients with active TAO of recent onset and thyroid autoimmunity without
      ophthalmopathy were tested for reactivity against purified native 64-kDa protein
      in immunoblotting. Tests were positive in 64% of patients with TAO, in 37.5% of
      those with Graves' hyperthyroidism without eye disease, in 11% of patients with
      Hashimoto's thyroiditis without eye disease, and in 13% of normal subjects. Many
      of the same sera were also tested for cytotoxic activity against human EM cells
      in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. ADCC tests were
      positive in 69% of patients with TAO but in no normal subject. The specificity
      and sensitivity of these two tests in TAO surpass those for all other published
      results for orbital tissue reactive autoantibodies. Although there was a tendency
      for a relationship between reactivity to the 64-kDa protein and cytotoxic
      activity against EM cells in ADCC there were many exceptions and overall the
      relationship between the two tests was not significant.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7580270
TI  - Amyloid goiter in cystic fibrosis.
AB  - Chronic infectious or inflammatory diseases lead to amyloid infiltration and
      dysfunction of many organs, including the kidney, liver, heart, and
      gastrointestinal tract. Subclinical amyloid infiltration of the thyroid gland has
      been described in over 80% of such patients. However, symptomatic involvement of
      the thyroid gland by amyloid is rare. We describe a euthyroid patient with cystic
      fibrosis and widespread amyloidosis who presented with a rapidly enlarging goiter
      and symptoms of local compression that compromised his pulmonary status. Fine
      needle aspiration of the goiter was nondiagnostic. At surgery he proved to have
      replacement of the thyroid gland by amyloid. A review of the literature reveals
      only five previous cases of amyloid goiter in patients with cystic fibrosis.
      However, as more patients survive into adulthood, amyloid goiter may become a
      more common complication of cystic fibrosis. In contrast to other patients with
      reactive amyloidosis and goiter, patients with cystic fibrosis may require
      thyroid surgery to relieve airway compression that can compromise pulmonary
      function.

PMID- 7580271
TI  - Metastatic follicular thyroid carcinoma masquerading as a chordoma.
AB  - A 61-year-old Caucasian man presented with otalgia, dysarthria, and weight loss.
      Neurological examination revealed palatal hypomotility, and weakness of the
      facial and tongue muscles. Magnetic resonance imaging of the head demonstrated
      the presence of a soft tissue mass in the clivus. Histologic examination of
      resected tumor disclosed well-differentiated thyroid follicles that invaded the
      local osseous tissues. Physical examination and radioiodine images of the thyroid
      gland were normal. The serum thyroglobulin concentration was markedly elevated
      (1011 ng/mL). A 0.9-cm well-differentiated benign-appearing left thyroid lobe
      follicular neoplasm with a thick fibrous capsule was found following diagnostic
      thyroidectomy. This report illustrates that clinically significant distant
      metastases can arise from occult follicular thyroid neoplasms that, according to
      standard histologic criteria, are benign. The presence of a thick fibrous
      capsule, even in the absence of vascular or capsular invasion, may identify
      follicular neoplasms that have metastatic potential.

PMID- 7580273
TI  - Medical management of Graves' ophthalmopathy.
AB  - In most patients with Graves' hyperthyroidism the eye signs are self-limiting and
      mostly subclinical. However, about one-third of the patients have clinically
      relevant ophthalmopathy, which can be disabling and disfiguring. The mechanical
      causes of the symptoms and signs of the eye disease are largely understood, but
      the best way to manage the ophthalmopathy is still a matter of much debate.
      Adequate treatment of hyperthyroidism can aleviate the eye symptoms to some
      extent, but it is less clear which kind of antithyroid treatment is to be
      preferred in patients with ophthalmopathy. There is particular controversy about
      the possibly deleterious effect of radioiodine therapy on the ophthalmopathy; in
      view of the present evidence it seems prudent to refrain from using 131I and to
      prefer antithyroid drugs in patients with clinical ophthalmopathy. Further
      medical management can include immunosuppressive treatment (such as
      corticosteroids) that results in improvement in roughly two-thirds of the
      patients. Orbital irradiation appears to be the first choice for treatment in
      moderately severe ophthalmopathy because it is equally effective and much better
      tolerated than classical corticosteroid treatment. However, to really improve the
      efficacy of such interventions we should be able to select those patients that
      are likely to respond to immunomodulatory therapy. Disease activity is probably
      the prime determinant of response and it is a challenge for the future to develop
      reliable parameters of disease activity on the basis of which patients can be
      selected for further medical treatment, or can be subjected to rehabilitative
      surgery without prior immunosuppression.

PMID- 7580275
TI  - 11th International Thyroid Congress. Toronto, Ontario, Canada, September 10-15,
      1995. Abstracts.

PMID- 7580279
TI  - District health boards need nurses.

PMID- 7580272
TI  - Inhibition of iodide transport in rat thyroid cells using N-substituted
      anthranilic acid derivatives.
AB  - The purpose of this study was to test the effects of chloride channel blockers on
      iodide uptake in thyroid cells, in the hope of eventually using these blockers to
      identify and isolate a putative iodide transporter. The chloride channel blockers
      used in this report are derivatives of N-substituted anthranilic acid and were
      synthesized using published procedures. For these studies FRTL-5 cells, a line of
      continuous-growing rat thyroid cells, were used as a model system to study
      effects on iodide transport. In these cells, there are at least two ways for
      transmembrane iodide movements, a sodium-dependent influx step and a proposed
      channel that normally mediates iodide efflux. Two derivatives studied decreased
      iodide accumulation in FRTL-5 cells, but were found also to lower intracellular
      pH and ATP levels. To simplify interpretation of the effect of the drugs on
      iodide transport, we extended the studies using plasma membrane vesicles made
      from pig thyroid. Iodide entry in these vesicles depended on a sodium gradient
      and was independent of ATP levels. Iodide transport in plasma membrane vesicles
      and FRTL-5 cells was measured at 30 sec when the uptake was nearly linear and
      therefore likely to reflect iodide entry. The uptake was measured using three
      concentrations of iodide and three of drug. Kinetic analysis of the data
      described a competitive inhibition by the drugs with a Ki of approximately 250
      microM. In summary, N-substituted anthranilic acid derivatives reversibly inhibit
      iodide entry in FRTL-5 cells and pig plasma membrane vesicles.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7580274
TI  - Thyroid hormone treatment of depression.
AB  - The use of thyroid hormones in the treatment of depression is reviewed. The
      studies examining the use of triodothyronine (T3) alone as well as combination
      with antidepressants are discussed. The data suggest that there is little
      evidence that T3 alone has antidepressant efficacy but that this hormone may be
      used to enhance therapeutic effects of antidepressants in treatment refractory
      depressed patients. The different theories to explain the antidepressant effects
      of T3 are summarized.

PMID- 7580280
TI  - The beginning graduate nurse in Saskatchewan. Evaluating and revising the
      competency profile.

PMID- 7580282
TI  - Keeping track of psychomotor skill.

PMID- 7580281
TI  - New approval process for Saskatchewan nursing education programs.

PMID- 7580283
TI  - Nurse alert! An open letter to all registered nurses.

PMID- 7580284
TI  - Reference intervals for human peripheral blood lymphocyte subpopulations from
      'healthy' young and aged subjects.
AB  - Some lymphocyte subpopulations change during aging but age-related reference
      limits from a healthy reference population are still lacking. In this study, we
      compiled 90% reference intervals for commonly determined lymphocyte
      subpopulations in 'healthy' (Senieur-compatible) young (20-32 years) and elderly
      (65-74 years) subjects. The most striking age-related changes included increases
      in HLA-DR+ T lymphocytes, and the shift in the expression of CD45 isoforms from
      the CD45RA+CD45RO-to the CD45RA-CD45RO+ subset. Both age-related alterations
      occurred in the CD4+ as well as in the CD8+ subpopulations and most of them were
      present in the relative and absolute number of lymphocyte subsets. We compare our
      data with those from previous investigations on lymphocyte subpopulations from
      the elderly and comment on useful presentation of reference values.

PMID- 7580285
TI  - Blood monocytes in rheumatoid arthritis are highly adherent to cultured
      endothelium.
AB  - Monocytes from 17 patients with rheumatoid arthritis (RA) were more adherent than
      monocytes from 17 control patients to monolayers of pig aortic endothelium
      irrespective of whether sera was included (median 27-34% increase; p = 0.002) or
      omitted (median 27% increase; p = 0.022) from the culture media. When human
      umbilical vein endothelial cells were used as the adherence substrate, rheumatoid
      monocytes from an additional 21 patients demonstrated a median 31% (p = 0.004)
      and 20% increase (p = 0.004) in adhesion when compared with monocytes from 21
      normal healthy subjects in the absence and presence of autologous sera,
      respectively. Activation of control monocytes with muramyl dipeptide or treatment
      with RA sera increased their attachment to endothelium (mean 34 +/- 14% increase;
      p < 0.001). The expression of the adhesion molecules CD11b (p < 0.005), CD18 (p <
      0.005), CD62L (p = 0.01) was enhanced on rheumatoid monocytes, but antibody
      blocking studies suggested that CD18 and CD62L were not responsible for the
      augmented binding of the rheumatoid cells. A subpopulation of rheumatoid
      monocytes possessed a very low net negative surface charge, a property that
      favours binding to vessel walls. We propose that many rheumatoid monocytes are
      predisposed for sheer-resistant adhesion to vascular endothelium.

PMID- 7580286
TI  - Effect of CC chemokines on mediator release from human skin mast cells and
      basophils.
AB  - Chemokines are considered important mediators of various inflammatory processes.
      In human basophils, different CC chemokines are known to stimulate release of
      histamine and generation of leukotriene (LT)C4. In the present study, we have
      evaluated the effect of RANTES (regulated upon activation, normal T cell
      expressed and secreted), monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3,
      macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta on mast cell
      activation. Whereas all these CC chemokines caused dose-dependent release of
      histamine from basophils in mixed human leukocyte suspensions, none of them was
      able to induce release of histamine as well as tryptase or prostaglandin (PG)D2
      from human skin mast cells, nor did priming with these substances enhance IgE
      mediated mediator release. In addition, all chemokines failed to promote changes
      in the cytosolic free calcium level in the human mast cell line HMC-1. These
      results add further evidence for the differences between human mast cells and
      basophils regarding cytokine-dependent activation.

PMID- 7580287
TI  - Phenotypic changes among hybrid rat mast cells.
AB  - Rat peritoneal mast cells and 6-thioguanine-resistant rat basophilic leukemia
      cells, representative of connective tissue-type (CTMC) and mucosal (MMC) mast
      cells, respectively, were fused using polyethylene glycol. Four out of 14 primary
      hybrid mast cell lines contained more than 50% of CTMC as demonstrated by
      histochemical staining. Two cell lines, one predominantly of the CTMC and the
      other of the MMC phenotype, were selected for further study. Among these, the
      phenotype was also confirmed by analysis for rat mast cell protease I and by
      mediator release triggered by compound 48/80 and ionophore A23187. The CTMC
      phenotype disappeared after culturing cells for 2 weeks. The change in phenotype
      did not significantly alter the mediator release due to calcium ionophore A23187.
      Repeated cloning of cells bearing the CTMC phenotype did not yield a cloned line
      of cells expressing the CTMC phenotype only, although it prolonged the
      persistence of this phenotype. During the period of CTMC phenotype loss, a drop
      in cellular DNA content occurred, suggesting that chromosome instability may, at
      least partially, have been responsible for the phenotypic changes.

PMID- 7580288
TI  - Effect of in vivo and in vitro lovastatin treatment on mast cell activation.
AB  - The hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin is
      used to treat hyperlipidaemia. This agent prevents the isoprenylation of some
      proteins involved in signal transduction processes and inhibits IgE-receptor
      linked mediator release from RBL-2H3 cells. In this study the effect of in vivo
      and in vitro administration of lovastatin on histamine release from rat
      peritoneal mast cells was examined. Lovastatin (4 mg/kg/day for 2 weeks)
      inhibited histamine release induced by concanavalin A (con A) from rat peritoneal
      mast cells of Hooded-Lister rats and both homozygous lean and obese Zucker rats.
      In contrast, release induced by antirat IgE (anti-IgE) was only significantly
      inhibited in cells derived from Hooded-Lister rats and that induced by compound
      48/80 was not altered. Lovastatin (20 microM, 24 h, in vitro) caused a
      significant inhibition of the subsequent histamine release to con A, anti-IgE and
      compound 48/80 but not to the calcium ionophore A 23187. It is important to
      determine whether such inhibitory effects are also observed after the chronic,
      clinical administration of lovastatin and other HMG CoA reductase inhibitors.

PMID- 7580289
TI  - High affinity IgE receptor-mediated prostaglandin E2 production by monocytes in
      atopic dermatitis.
AB  - High affinity IgE receptor (Fc epsilon R I) expression on monocytes and its
      upregulation on monocytes from patients with atopic dermatitis (AD) have been
      recently reported. In this study, we investigated whether prostaglandin E2 (PGE2)
      release from AD monocytes was Fc epsilon R I-dependent or not. The monocytes were
      stimulated with anti-Fc epsilon R I monoclonal antibody (mAb) and anti-Fc epsilon
      R II mAb. Cross-linking of Fc epsilon R I, but not that of Fc epsilon R II
      induced PGE2 release from monocytes. In order to confirm that the PGE2 release is
      IgE-dependent, stimulation with IgE+anti-IgE, IgG+anti-IgG and immune complexes
      made by incubation with AD patients' serum and recombinant Der fII (rDer fII-IC)
      were carried out in the culture. Significant PGE2 release by all the stimulants
      was observed, as compared with spontaneous release. PGE2 release by immune
      complex made by incubation with IgE-absorbed AD serum and rDer fII was much lower
      than that by rDer fII-IC. In monocytes from nonatopic donors, significant PGE2
      release was observed when stimulated with IgE+anti-IgE, IgG+anti-IgG, rDer fII
      IC, but not with anti-FC epsilon R I mAb and anti-Fc epsilon R II mAb. However,
      the release were significantly lower than respective PGE2 releases from AD
      monocytes. Taken together, cross-linking of Fc epsilon R I and IgE induced a PGE2
      release from monocytes. This is a first report demonstrating an Fc epsilon R I
      dependent mediator release from monocytes of AD patients.

PMID- 7580291
TI  - Histamine activates bronchial epithelial cells to release inflammatory cytokines
      in vitro.
AB  - Airway epithelial cells have a potential to produce cytokines which are relevant
      to airway inflammation. To elucidate the mechanisms of their regulation, we
      focused on the effects of three chemical mediators [histamine, platelet
      activating factor (PAF) and endothelin-1] important in the pathogenesis of
      bronchial asthma. Histamine, but not PAF or endothelin-1, showed a dose-dependent
      stimulatory effect on the release of interleukin-6, interleukin-8 and granulocyte
      macrophage colony-stimulating factor by normal and transformed human bronchial
      epithelial cells when studied 6 h after the treatment. The process required
      protein synthesis as evaluated by the effect of cycloheximide, and was mainly via
      H1 receptor. We concluded that histamine might be involved in the activation of
      airway epithelial cells to release inflammatory cytokines in allergic responses.

PMID- 7580290
TI  - N-terminus of a major allergen, Alt a I, of Alternaria alternata defined to be an
      epitope.
AB  - A 20mer peptide representing the N-terminus of a major allergen, Alt a I, of
      Alternaria alternata was synthesized and examined for its antibody binding and
      antibody induction activities. Alt a I peptide-BSA conjugate reacted with both
      human IgE and rabbit anti-Alt a I IgG in ELISA, albeit the binding of the peptide
      to IgE was relatively weak. Control conjugate showed no antibody binding. These
      results indicated that the N-terminus of Alt a I is an antibody binding site.
      Moreover, peptide-KLH conjugate and nonconjugated peptide induced both IgG and
      IgE antibodies in Balb/c mice that recognized both native Alt a I allergen and
      peptide-BSA conjugate. Since the free peptide was able to induce antibodies in
      vivo, the peptide may also possess a T cell epitope.

PMID- 7580292
TI  - Intranasal instillation of diesel exhaust particulates and antigen in mice
      modulated cytokine productions in cervical lymph node cells.
AB  - To investigate cytokine production stimulated by diesel exhaust particulates
      (DEP) and antigen through the intranasal route, mice were administered with DEP
      mixed with ovalbumin (OA) 3 times at an interval of 3 weeks. After the last
      instillation, cervical lymph node cells (LNC) were cultured in vitro with OA and
      antigen-presenting cells. The proliferative response to OA in cervical LNC from
      mice instilled with DEP and OA was noted to have increased significantly compared
      to mice instilled with OA alone. Interleukin 4 (IL-4) and interferon (IFN)-gamma
      in culture supernatants were measured with ELISA. OA-stimulated IL-4 production
      in cervical LNC from mice instilled with DEP and OA markedly increased beyond
      that in the control mice. In contrast, OA-stimulated IFN-gamma production in
      cervical LNC from mice instilled with OA was 3 times that for DEP and OA
      instilled mice. OA-specific IgE antibody in sera showed a trend to be increased
      in mice intranasally instilled with DEP and OA. These results suggest that
      intranasal instillation of DEP and antigen in mice may modulate in vitro antigen
      stimulated cytokine production from cervical LNC with a consequent increase in
      IgE antibody production.

PMID- 7580293
TI  - Airway responses following intradermal sensitization to different types of
      allergens: ovalbumin, trimellitic anhydride and Dermatophagoides farinae.
AB  - Sensitization of guinea pigs by intradermal injections of the occupational
      allergen trimellitic anhydride (TMA) in oily vehicle has been shown to be very
      reproducible. We studied the effect of intradermal sensitization with ovalbumin
      (OA) in oily vehicle on immune and airway responses in guinea pigs. We also
      compared airway responses to trimellitic anhydride or Dermatophagoides farinae
      (DF; mite) with those to OA in guinea pigs intradermally sensitized to respective
      allergens. Three to four weeks after sensitization, the animals were challenged
      with intratracheal instillation of these allergens. Intradermal injections with
      OA developed dose-dependently specific IgG1 antibodies to OA demonstrated by
      ELISA. In animals sensitized with different doses of OA in corn oil vehicle, a
      challenge with OA induced a reversely dose-dependent airflow obstruction and
      airway plasma exudation. In contrast, animals sensitized with OA in saline
      vehicle had dose-dependent airway responses to OA. Challenge with OA caused an
      immediate peak and subsequently persistent airflow obstruction, whereas this
      response to either TMA guinea pig serum albumin or Df was slowly progressive in
      animals sensitized to respective allergens. The animals sensitized to TMA or Df
      may show a different profile of airway responses following the challenge compared
      to OA. Intradermal sensitization may be a valuable method of sensitization for
      the development of an animal model of airway allergy to different types of
      allergens, including chemicals or mites.

PMID- 7580294
TI  - Pulmonary hypertension in rats. 1. Role of bromodeoxyuridine-positive mononuclear
      cells and alveolar macrophages.
AB  - The role of activated cells determined by staining with bromodeoxyuridine (BrdU)
      and the role of alveolar macrophages as a source of cytokines were investigated
      in monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. BrdU was
      mainly incorporated by mononuclear cells; their number increased strikingly prior
      to the development of PH. Cytokines such as interleukin (IL)-1, IL-6 and tumor
      necrosis factor were produced during the development of PH. The amount of IL-6
      showed significant correlation (p < 0.05) with the number of BrdU-positive cells,
      which, in turn, correlated with the extent of PH. These results indicate that
      BrdU-positive cells and cytokines produced by alveolar macrophages may play an
      important role in the pathogenesis of MCT-induced PH in rats.

PMID- 7580296
TI  - Effect of azelastine on endotoxin-induced airway hyperresponsiveness in mice.
AB  - We examined the role of lipopolysaccharide (LPS) on the pulmonary inflammatory
      process in mice, including the release of interleukin-1 (IL-1) and tumor necrosis
      factor-alpha (TNF-alpha) by macrophages, and investigated the mechanism of action
      of azelastine (AZ) on the release of these two cytokines. Intratracheal
      instillation of 1.0 microgram/ml LPS into BALB/c mice caused a significant
      increase in both IL-1 beta and TNF-alpha in aqueous lung extracts. These changes
      were modified, under control conditions, by a single dose of 0.05 mg/kg of AZ
      administered 1 and 11 h after LPS infusion. Intratracheal instillation of LPS
      also caused a significant increase in bronchial hyperresponsiveness to
      methacholine (Mch). AZ significantly inhibited Mch responsiveness in LPS-infused
      mice compared with nontreated control mice. Our results suggested that
      intratracheal instillation of LPS induces the secretion of macrophage cytokines
      in the airways of mice, accounting, at least partly, for LPS-induced airway
      hyperresponsiveness. Our results also indicate that the attenuating effect of AZ
      on LPS-induced airway hyperresponsiveness could be explained by its inhibitory
      effect on macrophage cytokine production.

PMID- 7580295
TI  - Pulmonary hypertension in rats. 2. Role of interleukin-6.
AB  - We administered human interleukin (IL)-6 to rats to examine whether it is
      implicated in the development of pulmonary hypertension (PH). The rats injected
      with IL-6 developed PH as determined by the weight ratio of the right ventricle
      to the left ventricle+septum. This ratio decreased with the appearance of IgG
      anti-human IL-6 antibody. Histologically we observed in the lungs, luminal
      occlusion of small muscular arteries, capillaries filled with fibrin thrombi, and
      localized hemorrhage. IL-6 increased the number of platelets, and the number of
      platelets correlated with the extent of PH. Thus, it seems likely that (IL-6) is
      involved in the formation of PH in this model.

PMID- 7580297
TI  - Protective effect of sodium cromoglycate on lipopolysaccharide-induced bronchial
      obstruction in asthmatics.
AB  - Lipopolysaccharides (LPS, the major part of endotoxins) are bacterial
      proinflammatory substances which can induce in asthmatic patients after
      inhalation a bronchial obstruction with an increase in both histamine bronchial
      hyperresponsiveness and blood inflammatory markers. The aim of the present study
      was to evaluate whether an acute inhalation of sodium cromoglycate, an anti
      inflammatory and membrane-stabilizating agent, can block the LPS-induced lung
      function response. Using a double-blind placebo-controlled crossover method, 7
      asthmatic subjects were submitted, at 4 days' interval, to a bronchial challenge
      test with either solvent solution or LPS (20 micrograms) preceded by inhalation
      of sodium cromoglycate (10 mg) or placebo. Compared to the solvent reaction, LPS
      induced a significant bronchial obstruction [measured by both the forced
      expiratory volume in 1 s (FEV1) and the airway resistances] beginning at the 60th
      minute and lasting more than 300 min (p < 0.01, 2-way ANOVA). On the other hand,
      acute pretreatment with sodium cromoglycate significantly inhibited the LPS
      induced bronchial obstruction. The total lung capacity did not change
      significantly after LPS inhalation. Thus, this study showed that in asthmatics
      the LPS-induced FEV1 response is blocked by acute treatment with sodium
      cromoglycate. Sodium cromoglycate could be an active treatment in asthmatics
      exposed to house dust containing endotoxin.

PMID- 7580298
TI  - Global aspects of vaccination.
AB  - The prospects for many children born in developing countries to reach adulthood
      has been transformed over the last 30 years by the activities of the Expanded
      Programme of Immunization (EPI) established by the World Health Organization
      (WHO) in 1974. By 1990, about 80% of children had been vaccinated against six
      common childhood diseases. The advent of new technologies provided a strong
      stimulus to those involved in vaccine design, development and delivery, and
      offered the possibility of improving current vaccines, developing new vaccines
      and simplifying vaccination practices. This in turn led to the formation of the
      Children's Vaccine Initiative (CVI) in the early 1990s. The worldwide emergence
      of new diseases such as HIV/AIDS and the re-emergence of old diseases such as
      tuberculosis and cholera present additional challenges.

PMID- 7580299
TI  - Vaccination against tuberculosis.
AB  - Recent findings in mice have changed our perception of how protective immunity
      works in tuberculosis and hold promise for the rapid development of new vaccines.
      For example, we now know: (1) that a single mycobacterial protein antigen can be
      sufficient to generate powerful protective immunity, provided that it is
      presented to the immune system in the right way; (2) that the expression of
      protection depends on cytotoxic antigen-specific T cells; (3) that the identity
      of the antigen may be less important than the mode of presentation, and (4) that
      injection of DNA encoding the antigen (DNA vaccination) is a superior way of
      raising protective immunity compared to injection of the antigen itself. These
      advances are timely because there is an urgent need for a new vaccine against
      tuberculosis. There continue to be about 3 million deaths from tuberculosis every
      year worldwide and increasingly the causative bacteria are multidrug resistant.

PMID- 7580300
TI  - Progress in AIDS vaccine development.
AB  - Because of a unique combination of challenges facing human immunodeficiency virus
      vaccine developers, a number of traditional and novel vaccine designs are being
      evaluated essentially in parallel. Monomeric proteins, poxvirus vectors,
      peptides, and particle-based candidate vaccines have entered or will soon enter
      human trials. Other designs are at earlier stages of development. All candidates
      evaluated to date in phase I/II human trials have proven safe and immunogenic.
      One or more of the most promising designs will soon progress to 'test of concept'
      clinical trials to determine efficacy.

PMID- 7580301
TI  - Influenza vaccines.
AB  - This is a report about influenza vaccines. Recommendations for the 1995/1996
      influenza season vaccine components are cited. There are many different types of
      influenza vaccine, but only inactivated vaccines are licensed for parenteral
      administration in humans. Experimental live vaccines have been developed and
      evaluated for their usefulness in the immunoprophylaxis of influenza in humans,
      especially for those at high risk of death from influenza virus infection. The
      current inactivated vaccines do not provide complete protection.

PMID- 7580302
TI  - Synthetic recombinant vaccines against viral agents.
AB  - Synthetic recombinant vaccines are expression vectors incorporating defined
      epitope(s) of microbial agents. They are prepared by inserting synthetic
      oligonucleotide(s) coding for previously identified relevant epitopes into the
      genome of a desired vector, using recombinant DNA technology. The results
      discussed indicate that immunization with such vaccines carrying viral epitopes
      may lead to protective immunity against viral agents. Oligonucleotides coding for
      three influenza epitopes stimulating B cells, T helper cells and cytotoxic
      lymphocytes were individually inserted into the flagellin gene of a Salmonella
      vaccine strain. Immunization of mice with the resultant recombinant bacteria or
      their isolated flagella induced a specific mucosal anti-influenza protective
      response. The most efficient vaccine consisted of all three recombinant flagella,
      administered intranasally. The protection elicited was cross-strain specific,
      long-lasting and efficient against a lethal viral challenge.

PMID- 7580304
TI  - Features of oral immunization.
AB  - In this review, we focus on some key areas concerning the unique properties of
      the mucosal immune system. They are: (1) the fact that the common mucosal immune
      system consists of different compartments; (2) the advantages of oral
      vaccination, which can be exploited to antigen-specific sIgA-mediated local
      immune responses as well as systemic immunity; (3) efficacious oral immunization
      against respiratory infections; (4) oral tolerance with respect to activation of
      T cells which, after declining, can be repeatedly reinduced without changes in
      profile or magnitude, and (5) the use of transgenic plants as a new vaccine
      source for a new vaccination strategy, i.e. employing edible dietary vaccines.

PMID- 7580303
TI  - Genetic detoxification of bacterial toxins: a new approach to vaccine
      development.
AB  - Chemically detoxified bacterial toxins (toxoids) have been successfully used as
      vaccines for the prevention of many bacterial infectious diseases. Today,
      nontoxic derivatives of bacterial toxins can be obtained by mutagenesis of the
      toxin genes. These genetically inactivated toxins are superior to the classical
      toxoids both in safety and in immunogenicity and therefore they should replace
      the old toxoids in the existing vaccines. In addition, they represent a novel
      class of immunogens with unique properties, some of which may be used for
      innovative approaches to vaccination.

PMID- 7580305
TI  - Tumor vaccine design: concepts, mechanisms, and efficacy testing.
AB  - This paper deals with the design of tumor vaccines for either prophylactic
      application, such as viral vaccines, or for therapeutic application in cancer
      patients. It discusses important aspects in the design of vaccines which come
      from experience in the fields of infectious diseases and autoimmunity. As
      examples of tumor vaccines which are presently being tested, virus-infected tumor
      cell vaccines and gene-transfected tumor cell vaccines are further discussed.
      Such live cell vaccines are compared with oncolysate vaccines or vaccines
      prepared from purified tumor antigens and adjuvants. Future perspectives of such
      approaches for biotherapy of cancer are also discussed.

PMID- 7580306
TI  - Vaccines to prevent and treat autoimmune diseases.
AB  - The current therapy for human autoimmune disease is based on nonselective
      immunosuppression achieved by corticosteroids or cytotoxic drugs. This form of
      therapy is toxic and frequently not effective in curing the disease. The study of
      experimental autoimmune disease models indicates that the pathogenic population
      of immune cells is restricted in terms of T-cell receptor gene usage and peptide
      epitopes recognized in the self-antigens. The recent developments in
      understanding of the pathophysiology of autoimmune disease point to the crucial
      role of the pathogenic T cell, the autoantigenic peptide, and the major
      histocompatibility complex molecules as well as the regulatory T-cell population
      in the disease process. The purpose of this review is to describe the use of
      vaccines to prevent and treat autoimmune disease. Encouraging results in animal
      models using vaccines based on the pathogenic T cell or the autoantigen have
      prompted the design of novel and selective immune-based therapies for human
      autoimmune disease.

PMID- 7580308
TI  - Induction of antigen-specific unresponsiveness with synthetic peptides: specific
      immunotherapy for treatment of allergic and autoimmune conditions.
AB  - Current drug-based therapies for autoimmune and allergic conditions are non
      specific and often associated with severe side effects. Recent advances in our
      knowledge of how T cells see antigens points to an improved strategy. T
      lymphocytes recognise processed forms of antigen which can be mimicked by
      synthetic peptides designed and built in the laboratory. It is clear from recent
      work that these synthetic peptides, when given systemically in solution, induce a
      state of hyporesponsiveness in naive T cells thereby specifically preventing a
      subsequent immune response. Moreover systemic administration of soluble peptides
      can inhibit ongoing immune responses. Taken together this new information offers
      great promise for future development of antigen-based drugs for the treatment of
      autoimmune and allergic diseases.

PMID- 7580309
TI  - Streptococcus-mutans-induced nephritis in rabbits: rheumatoid factors and
      nephritogenicity.
AB  - The pathogenesis of streptococcus-induced nephritides (SIN) involves immune
      complex-mediated inflammation; however, specific mechanisms are still poorly
      understood. Using preparations of two strains of Streptococcus mutans (SM) in
      attempts to induce SIN in rabbits, one preparation was strongly and the other
      virtually not nephritogenic. The non-nephritogenic preparation provided a
      negative control for our studies. Streptococcal components were present in
      circulating immune complexes (CIC) as well as in tissue-bound immune complexes
      (TIC), especially early in the disease. CIC and TIC also contained rheumatoid
      factors (RF), which tended to predominate in late stages of the disease. The
      nephritogenic and the non-nephritogenic preparations of SM shared the same major
      tissue-binding components and induced similar titers of antimicrobial antibodies,
      but differed significantly in their ability to induce CIC and RF. It is proposed
      that kidney-binding microbial components, antimicrobial antibodies and high serum
      concentration of RF are necessary and sufficient determinants for the
      pathogenesis of SIN in this rabbit model.

PMID- 7580307
TI  - Vaccination for birth control.
AB  - The global population is currently expanding at the unprecedented rate of nearly
      1 billion per decade, with 94% of the increase occurring in the developing world.
      New methods of fertility regulation are urgently needed, and the development of
      birth control vaccines by active immunization against antigens specific for
      reproduction has made substantial progress during the last two decades. These
      vaccines are meant to have an outstanding impact on future control of worldwide
      population growth by providing safe, effective, long-lasting and reversible
      contraception. The most advanced of these vaccines are based on the placental
      pregnancy hormone human chorionic gonadotropin (hCG), and have already entered
      clinical trials. However, immunological cross-reactivity and lack of efficacy of
      anti-hCG antibodies seriously challenge this strategy. Conversely, efforts to
      understand the molecular events involved in the fusion of sperm and egg have led
      to the identification of new target structures for the development of fertility
      regulating vaccines. Herein, we summarize the current state of birth control
      vaccines and discuss the risks and drawbacks of this approach to fertility
      regulation.

PMID- 7580310
TI  - Heterogeneity of pollen proteins within individual Betula pendula trees.
AB  - To determine the variation of antigenic water soluble proteins in white birch
      (Betula pendula) pollen, extracts of pollen from different sides of individual
      trees were analyzed by isoelectric focusing (IEF), crossed immunoelectrophoresis,
      and crossed radioimmunoelectrophoresis. IgE-antibody-binding patterns were also
      studied in samples analyzed by IEF by probing with serum pooled from patients
      with birch pollen allergy, followed by radiolabelled anti-IgE. Antigenic proteins
      and allergens per unit weight of extracted protein were greatest in pollen
      extracts from the south side of the trees. Allergens decreased progressively in
      pollen from west-through east- to north- facing branches. Proteins with high
      isoelectric points (pI > 8.5) and proteins between pI 4.5 and 5.6 were infrequent
      in extracts from the north side. Extracts from branches facing north were poor in
      allergens: in general, only one or two precipitin lines were found, and in some
      cases they did not bind to IgE antibodies. Differences between numbers of
      proteins and allergens found in extracts from south, west and north branches were
      statistically significant for all methods used. The results indicate the need to
      collect birch pollen for allergen extract manufacture from south-facing branches.

PMID- 7580311
TI  - Evaluation of a liquid chromatographic method for the determination of fumonisins
      in corn, poultry feed, and Fusarium culture material.
AB  - The performance of a liquid chromatographic method for determining fumonisins in
      corn, animal feeds, and culture material was evaluated. Efficiencies of
      extractions with the following solvent systems were determined: acetonitrile
      water (50 + 50, v/v), methanol-water (75 + 25, v/v), and 100% water. The
      acetonitrile solvent gave both higher extraction efficiencies and faster
      extraction times than the other 2 solvents. Extraction was followed by C18 solid
      phase extraction column cleanup. Fumonisin B1 (FB1), fumonisin B2 (FB2), and
      fumonisin B3 (FB3) were measured by precolumn derivatization with o
      phthalaldehyde followed by isocratic separation on a C18 reversed-phase column
      with a mobile phase of 50 mM potassium dihydrogen phosphate (pH 3.3)-acetonitrile
      (60 + 40). Commercially prepared poultry feed, corn, and Fusarium spp. corn
      cultures were analyzed at the following levels: FB1, 1.5 to 15,000 micrograms/g;
      FB2, 0.5 to 4000 micrograms/g; FB3, and 0.17 to 1,500 micrograms/g. Recoveries
      were 91-94%, 90-100%, and 81-93% for FB1, FB2, and FB3, respectively. Precision
      (coefficient of variation) was determined with pooled field samples and ranged
      from 2% at 19 micrograms/g for FB1 to 9% at 0.17 microgram/g for FB3. Time and pH
      studies of the formation of the fluorescent derivative and its stability were
      conducted. Complete reaction occurred at pHs above 7.9, with optimal pH for
      chromatography between 8.0 and 8.5. No statistically significant response
      differences were detected for reaction times ranging from 4 to 40 min; however,
      the detector signal was significantly reduced when reaction times were shorter
      than 4 min. Chromatograms of samples were free of interferences for all feeds,
      corn, and culture material tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580312
TI  - Evaluation of sampling plans used in the United States, United Kingdom, and The
      Netherlands to test raw shelled peanuts for aflatoxin.
AB  - The United States is a large producer and exporter of peanuts. The United Kingdom
      and The Netherlands are major importers of U.S. peanuts. Each country has a
      different guideline or legal limit for peanut products containing aflatoxin.
      Peanuts are tested for aflatoxin in each country by using specifically designed
      aflatoxin sampling plans to determine if the aflatoxin concentration in a lot of
      raw shelled peanuts is less than the guideline or legal limit. For raw shelled
      peanuts, the U.S. plan has the highest sample acceptance limit of 15 ng total
      aflatoxin/g, the UK plan has a sample acceptance limit of 10 ng total
      aflatoxin/g, and the Dutch Code of Practice (called the Dutch plan) has the
      lowest sample acceptance limit at 3 ng aflatoxin B1/g. The U.S. plan uses a
      maximum of 3 sampling units, each weighing 21.8 kg; the UK plan uses a single
      sampling unit of 10 kg; and the Dutch plan uses 4 sampling units, each weighing
      7.5 kg. The sampling variance is lowest for the U.S. plan and highest for the
      Dutch plan. The sample preparation variance is lowest for both the Dutch and UK
      plans and highest for the U.S. plan, primarily because of the mill type used to
      comminute the kernels in the sample. For a given distribution among lot
      concentrations, the U.S. plan accepts the greatest number of lots and the Dutch
      plan rejects the greatest number of lots. The average aflatoxin concentration
      among accepted lots is highest for the U.S. plan and lowest for the Dutch
      plan.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580313
TI  - Liquid chromatographic determination of trans-10-hydroxy-2-decenoic acid content
      of commercial products containing royal jelly.
AB  - Thirty-nine samples of commercial products containing royal jelly were analyzed
      by liquid chromatography for their trans-10-hydroxy-2-decenoic acid (10-HDA)
      content. Most of the samples contained 10-HDA. Samples claimed to be pure royal
      jelly contained 1.98 to 6.37% 10-HDA (w/w). The 10-HDA content of samples claimed
      to contain royal jelly as an ingredient ranged from nondetectable to 1.28% (w/w).

PMID- 7580314
TI  - Rapid spectrophotometric method for analyzing natamycin in cheese and cheese
      rind.
AB  - A rapid spectrophotometric method for determining natamycin in cheese and cheese
      rind has been developed. Samples are homogenized with acidified aqueous
      acetonitrile and homogenates are filtered. Natamycin is directly quantitated in
      filtered extracts on the basis of the characteristic third-derivative trough at
      322.6 nm. Additional cleanup of extracts is not required because derivative
      transformation of the conventional analytical band at around 319 nm eliminates
      spectral interferences from other compounds. The analysis is simple and can be
      completed in 6 min. The equipment is easily accessible because most modern
      spectrophotometers allow instant generation of derivative spectra. The method
      needs small amounts of solvents and has good analytical characteristics. Overall
      recovery was 98.4 +/- 0.7%, and linearity was excellent (r = 0.9998) in the range
      examined (0.5-20 mg/kg). Quantitation and detection-limits were estimated at 0.5
      and 0.25 mg/kg, respectively. Precision statistics based on within-day and
      between-days variations suggest an overall relative standard deviation of 1.4%.

PMID- 7580315
TI  - Total dietary fiber determined as neutral sugar residues, uronic acid residues,
      and Klason lignin (the Uppsala method): collaborative study.
AB  - A joint AOAC/American Association of Cereal Chemists (AACC) collaborative study
      was conducted to determine by the Uppsala method the dietary fiber content and
      its composition in various foods. The method includes preparation of a residue by
      treatment with thermostable alpha-amylase and amyloglucosidase and then ethanol
      precipitation of solubilized dietary fiber components while leaving low-molecular
      weight carbohydrates in solution. After acid hydrolysis of residue, neutral
      polysaccharide residues are determined as alditol acetates by gas-liquid
      chromatography, uronic acid residues are determined by colorimetry, and ash-free
      acid-insoluble residue (Klason lignin) is determined gravimetrically. Total
      dietary fiber, including enzyme-resistant starch, is calculated as the sum of
      nonstarch polysaccharide residues and Klason lignin. Nine laboratories completed
      the study, analyzing in duplicate 8 unknown dried products that included 4 cereal
      products, green peas, potato fiber, carrots, and apples. Total dietary fiber
      contents of products tested ranged from 4.6 to 84.3%, with an average RSDR value
      of 8.4% (range, 4.8-11.1%). Total neutral polysaccharide residues ranged from 3.8
      to 64.1%, with an average RSDR value of 7.5% (range, 5.4-10.5%). Individual
      neutral sugars (rhamnose, arabinose, xylose, mannose, galactose, and glucose) and
      uronic acid residues present at more than 1% generally had good RSDR values (3.3
      22.8%), whereas, as expected for Klason lignin, only the wheat bran sample with a
      high content (16%) had an excellent RSDR value (5.0%). The gas chromatographic
      colorimetric-gravimetric method (Uppsala method) for determination of total
      dietary fiber (as neutral sugar residues, uronic acid residues, and Klason
      lignin) has been adopted first action by AOAC INTERNATIONAL.

PMID- 7580316
TI  - Liquid chromatographic method for determination of biogenic amines in fish and
      fish products.
AB  - A liquid chromatographic method with postcolumn derivatization is described for
      determination of biogenic amines in fish and fish products. Histamine, tyramine,
      serotonin, beta-phenylethylamine, tryptamine, putrescine, cadaverine, agmatine,
      spermine, and spermidine can be determined in less than 60 min. Routine sample
      preinjection treatment implies only 2 extractions with 0.6N perchloric acid and
      filtration through a 0.45 micron filter. Lack of interferences from volatile
      amines, amino acids, and dipeptides was verified. Results of reliability study
      were satisfactory. The proposed method was linear for each amine between 0.25 and
      8.00 mg/L. Average recoveries ranged from 92 to 103%. Precisions (coefficients of
      variation) ranged from 0.70 to 9.75%. Determination limits were < or = 1 mg/kg. A
      modification in LC conditions was necessary to apply the method to ripened fish
      products to avoid interferences from food matrixes. In addition, stability of
      biogenic amines in fresh anchovies and hake during short-term frozen storage was
      studied. Results showed that, except for agmatine, frozen storage is suitable for
      keeping samples before analysis.

PMID- 7580317
TI  - Analysis of polychlorinated biphenyls in fatty biological matrixes by on-line
      supercritical fluid extraction and supercritical fluid cleanup.
AB  - We present a method that combines the extraction of polychlorinated biphenyls
      (PCBs) and their separation from relatively large quantities of fat in biological
      matrixes by combined supercritical fluid extraction and separation. Cyano
      functionalized silica gel, silica gel, aluminum oxide, Florisil, 3-amino-propyl
      functionalized silica gel, and octadecyl-functionalized silica gel were tested
      for suitability as chromatographic media for separation of PCBs from lipids.
      Silica gel, 3-aminopropyl-functionalized silica gel, and Florisil adequately
      separated PCBs from lipids when eluted with supercritical CO2. Florisil allowed
      both the extraction of PCBs and their separation from lipids in PCB-spiked
      chicken egg and fish. Two grams of sample containing PCBs at 0.125 microgram/g
      was sufficient for subsequent separations and the low-level analysis required for
      the more toxic PCB components.

PMID- 7580319
TI  - Liquid chromatographic determination of simazine, atrazine, and propazine
      residues in catfish.
AB  - A liquid chromatographic (LC) method is described for the simultaneous
      determination of the triazine herbicides, simazine (SIM), atrazine (ATZ), and
      propazine (PRO) in the 12.5-100 ppb range in catfish. The herbicides are
      extracted from catfish homogenates with ethyl acetate, followed by solvent
      partitioning between acetonitrile and petroleum ether and additional cleanup on a
      C18 cartridge. A Supelcosil LC-18-DB column is used for LC separation, and UV
      determination is at 220 nm. The isocratic mobile phase is a mixture of methanol,
      acetonitrile, and water. Mean recoveries from catfish were 88.7, 96.9, and 91.7%;
      standard deviations were 6.84, 7.78, and 6.26%; and coefficients of variation
      were 7.72, 8.03, and 6.82% for SIM, ATZ, and PRO, respectively.

PMID- 7580318
TI  - Electrothermal atomic absorption spectrometric determination of cadmium, copper,
      iron, lead, and selenium in fruit slurry: analytical application to nutritional
      and toxicological quality control.
AB  - A method is described for direct determination of cadmium, copper, iron, lead,
      and selenium in slurried fruit samples by electrothermal atomic absorption
      spectrometry. The fresh samples were suspended in Triton X-100 and shaken with 10
      g zirconia spheres until a slurry was formed. The graphite furnace conditions
      were optimized for each element. The detection limits were 0.3, 3.5, 15.0, 0.5,
      and 10.0 ng/g for Cd, Cu, Fe, Pb, and Se, respectively. Accuracy and precision
      were checked against sample mineralization in a microwave acid-digestion bomb.
      Results for analyses of National Institute of Standards and Technology standard
      reference materials agreed closely with certified values. Analytical application
      of this method was tested with 40 samples of 8 widely consumed fruit species. The
      mean values (referred to fresh weight of edible fraction) for each fruit species
      had ranges of 0.0003-0.050 microgram/g for Cd, 0.316-1.094 micrograms/g for Cu,
      2.00-5.50 micrograms/g for Fe, 0.050-0.396 microgram/g for Pb, and 0.010-0.020
      microgram/g for Se. The proposed method is useful for routine multielemental
      analysis in nutritional and toxicological quality control of fruits and similar
      foodstuffs.

PMID- 7580320
TI  - Multivessel supercritical fluid extraction of food items in Total Diet Study.
AB  - An off-line, large capacity, multivessel supercritical fluid extractor (SFE) was
      designed and constructed for extraction of large samples. The extractor can
      simultaneously process 1-6 samples (15-25 g) by using supercritical carbon
      dioxide (SC-CO2), which is relatively nontoxic and nonflammable, as the solvent
      extraction medium. Lipid recoveries for the SFE system were comparable to those
      obtained by blending or Soxhlet extraction procedures. Extractions at 10,000 psi,
      80 degrees C, expanded gaseous CO2 flow rates of 4-5 L/min (35 degrees C), and 1
      3 h extraction times gave reproducible lipid recoveries for pork sausage
      (relative standard deviation [RSD], 1.32%), corn chips (RSD, 0.46%), cheddar
      cheese (RSD, 1.14%), and peanut butter (RSD, 0.44%). In addition, this SFE system
      gave reproducible recoveries (> 93%) for butter fortified with cis-chlordane and
      malathion at the 100 ppm and 0.1 ppm levels. Six portions each of cheddar cheese,
      saltine crackers, sandwich cookies, and ground hamburger also were simultaneously
      extracted with SC-CO2 and analyzed for incurred pesticide residues. Results
      obtained with this SFE system were reproducible and comparable with results from
      organic-solvent extraction procedures currently used in the Total Diet Study;
      therefore, use and disposal of large quantities of organic solvents can be
      eliminated.

PMID- 7580321
TI  - Immunoassay of pesticides: an update.
AB  - Measurement of levels of pesticides residues in foods and crops most often
      requires extensive cleanup and instrumental techniques such as gas
      chromatography. Immunoassay measurement techniques, on the other hand, may be
      used directly on the test portion or require only minimal cleanup. Further
      refinements of the common antibody-enzyme-based solid-phase assays, such as use
      of coated magnetic particles, antibody-coated crystals, and continuous-flow
      devices, have extended the measurement range and applicability of these assays.
      Likewise, new immunoassays for pesticides have been developed, and existing
      assays have been refined, optimized, and more completely characterized and
      validated. In addition to their ability to accurately and reliably measure
      amounts of residues present in food and crops, immunoassays can be readily used
      as rapid screening methods for contaminants in field samples. We have previously
      reviewed much of the work in the area of pesticide immunoassay; this report
      updates previous information and discusses some new immunoassay techniques.

PMID- 7580323
TI  - Enhancement of ethylenethiourea recoveries in food analyses by addition of
      cysteine hydrochloride.
AB  - The effectiveness of cysteine hydrochloride (Cys-HCl) as a preservative of
      ethylenethiourea (ETU) in product matrixes and during analysis was studied. ETU
      recoveries were adversely affected by certain product matrixes when fortified
      directly into the product. Recoveries in 8 selected food items were 0-92% when
      analyzed 30 min after fortification and 0-51% when analyzed after 24 h. When Cys
      HCl was added to product prior to fortification, recoveries increased to 71-95%
      even after frozen storage for 2-4 weeks. Cys-HCl was added during analysis of 53
      untreated items. Recoveries improved an average of 15% with Cys-HCl. Without Cys
      HCl, recoveries were erratic (20-98%), but with Cys-HCl, recoveries were 68-113%.
      Other antioxidants (sodium sulfite, butylated hydroxyanisole, butylated
      hydroxytoluene, and vitamins A and C) also were evaluated as ETU preservatives.
      When lettuce was treated first with sodium sulfite and then fortified with ETU,
      recoveries averaged 86%; without sodium sulfite, they averaged 1%. The other
      antioxidants were less effective for preserving ETU in lettuce, giving only 8-46%
      recoveries. The effect of oxidizers (potassium bromate, sodium hypochlorite, and
      hydrogen peroxide) on ETU recovery was also determined. Recovery of ETU from a
      baby food product (pears and pineapple) was 82%; with oxidizers, recoveries were
      0-8%.

PMID- 7580322
TI  - Determination of sulfonylurea herbicides in grains by capillary electrophoresis.
AB  - A capillary electrophoresis (CE) method was developed to separate and determine
      residues of 5 sulfonylurea herbicides in grains (wheat, barley, and corn). This
      work demonstrated the practicality of using CE for residue analysis of
      sulfonylureas. The method yielded good recoveries and adequate sensitivities at
      tolerance levels (0.05-0.1 ppm). The compounds investigated were metsulfuron
      methyl (Ally), thifensulfuron methyl (Harmony), chlorsulfuron (Glean),
      rimsulfuron (DPX-E9636), and tribenuron methyl (Express). Acetonitrile extracts
      of grain samples were partitioned with hexane and then cleaned up with cation
      exchange solid-phase extraction cartridges. Quantitation was performed by
      micellar electrokinetic capillary chromatography using a high-sensitivity optical
      cell. Average recoveries at the 0.05 ppm level ranged from 72.9 to 118.5%. The
      lower limit of detection was approximately 0.02 ppm, except for rimsulfuron and
      tribenuron methyl, for which the lower limit of detection was 0.035 ppm. The
      method was less complicated and showed better sensitivity than current single
      analyte liquid chromatographic enforcement methods.

PMID- 7580324
TI  - Hard surface carrier test as a quantitative test of disinfection: a collaborative
      study.
AB  - The hard surface carrier test (HSCT) recently was proposed as a qualitative test
      for disinfectant efficacy. A collaborative study of HSCT led to a suggested
      performance standard of < or = 2 or 3 positive carriers out of 60 tested.
      Subsequently, it was discovered that HSCT can be used as a quantitative test,
      because the HSCT protocol requires measurement of inoculum level on some
      carriers. The data allow estimation of the log10 reduction in number of active
      bacteria. Producers, consumers, and policymakers will be better able to discuss
      merits of alternative performance standards if the focus is on log reduction of
      organisms rather than on number of positive carriers. Data from the collaborative
      study were reanalyzed from this quantitative viewpoint. If the point estimate of
      log reduction in LR and the 99% lower confidence limit estimate is LLR, the LR
      values ranged from 7.0 to 9.0 and the LLR values were greater than 6.0 for all
      disinfectants except the negative control formulation. The total variance for
      estimated LR is the sum of interlaboratory and intralaboratory variances. The
      total variance for LR was 0.095 for Pseudomonas aeruginosa, 0.251 for
      Staphylococcus aureus, and 0.118 for Salmonella choleraesuis. Percentages of the
      variance due to interlaboratory variability were 11% for P. aeruginosa, 52% for
      S. aureus, and 25% for S. choleraesuis. Chances of making false-effective and
      false-ineffective decisions can be calculated for the quantitative HSCT. The
      performance standard can be based on LLR.

PMID- 7580325
TI  - Quality assurance in weighing.
AB  - Weighing is the most used step in any analytical procedure, and the balance is
      the one essential piece of laboratory equipment in all analyses. Yet weighing is
      a common source of error in final analytical results and can be difficult to
      detect. Analysts may become complacent and expect all weighings to be accurate.
      Our laboratory experienced a problem in weighing and found that the principal
      error was due to drift. The ensuing investigation into the cause led to a
      procedure for reducing drift, which, in turn, ensured accurate weighings that
      have improved quality assurance in our total operations.

PMID- 7580327
TI  - Liquid chromatographic determination of furazolidone in swine serum and avian
      egg.
AB  - A rapid, simple, and accurate method for determination of furazolidone (FZ) in
      swine serum and avian egg using liquid chromatography (LC) with a 358 nm
      ultraviolet-visible spectrophotometric detector is described. After liquid-liquid
      extraction of sample with ethyl acetate using Extrelut-3, the extract is
      evaporated, redissolved in 40% acetonitrile, and injected directly into the
      chromatograph. The antibiotic can be analyzed within 30 min. Within-day
      recoveries for swine serum and avian egg spiked with FZ at 1 ppm were 90.0 and
      88.1%, respectively, with coefficients of variation of 3.52 and 3.88%,
      respectively. Between days recoveries for the 1 ppm samples were 87.2 and 87.0%,
      with coefficients of variation of 3.10 and 4.29%, respectively. Determination of
      FZ also was performed by LC/mass spectrometry (MS) with an atmospheric-pressure
      chemical-ionization interface (APCI) system. The LC/MS-APCI system is more
      applicable for qualitative analysis than quantitative analysis because the drug
      detection limit (about 0.1 microgram/L) is almost the same as that of the LC-UV
      detector.

PMID- 7580326
TI  - Determination of methylmercury after supercritical fluid extraction.
AB  - A method, using supercritical fluid extraction, for determining methylmercury in
      seafood has been developed to eliminate use of toxic organic solvents. Seafood
      samples were treated with 1N NaOH and then acidified with HCl to release CH3HgCl.
      After mixing the sample with cellulose powder (40 mesh) containing stearic acid
      modifier at 5 mg/g, the extraction was performed with supercritical CO2 under the
      following conditions: pressure, 200 atm; temperature, 50 degrees C; time, 20 min;
      and trap, 0.01N Na2S2O3 in a conical tube immersed in a flask of warm water to
      prevent freezing. The extract was then analyzed by a suitable method, such as
      cold-vapor atomic absorption spectrophotometry. The accuracy of the procedure was
      verified by analyzing biological standard reference materials. Several commercial
      seafood samples and spikes have been analyzed.

PMID- 7580328
TI  - Survey of lead, cadmium, fluoride, nickel, and cobalt in food composites and
      estimation of dietary intakes of these elements by Canadians in 1986-1988.
AB  - During the period 1986-1988, foods were purchased at the retail level in 5
      Canadian cities and, for each city, prepared for consumption and combined into
      113 composites and 39 composite subsets. Lead and cadmium were determined in all
      the samples; fluoride, in samples from Winnipeg; and cobalt and nickel, in
      samples from Montreal. Means and ranges of concentrations (ng/g) found in
      individual samples were lead, 23.2 (< 0.4-523); cadmium, 9.96 (< 0.02-167);
      fluoride, 325 (11-4970); nickel, 196 (< 0.6-2521); and cobalt, 9.4 (< 0.3-75.7).
      Estimated dietary intakes (microgram/day) of the elements over all ages and sexes
      were lead, 24; cadmium, 13; fluoride, 1763; nickel, 286; and cobalt, 11. During
      the period 1985-1988, the average level of lead in canned foods decreased from
      73.6 to 46 ng/g.

PMID- 7580329
TI  - Dietary intakes of pesticides, selected elements, and other chemicals: FDA Total
      Diet Study, June 1984-April 1986.
AB  - The U.S. Food and Drug Administration conducts the Total Diet Study to determine
      dietary intakes of selected pesticides, industrial chemicals, and elements
      (including radionuclides). The results reported here reflect the sampling period
      from June 1984 to April 1986. The study involves retail purchase of foods
      representative of the total diet of the U.S. population, preparation for table
      ready consumption, and individual analyses of 234 items depicting the diets of 8
      population groups. The diets were based on 2 nationwide food consumption surveys.
      The data presented represent 8 food collections (also termed "market baskets") in
      regional metropolitan areas during the 2-year period. Dietary intakes of over 90
      analytes are presented for the 8 population groups, which range from infants to
      elderly adults. Intakes of selected population groups are compared with
      representative previous findings. As reported previously, average daily intakes
      are well below acceptable limits.

PMID- 7580330
TI  - Estimation of 1992-1993 dietary intake of organochlorine and organophosphorus
      pesticides in Fukuoka, Japan.
AB  - To estimate Japanese daily intakes of organochlorine pesticides such as
      hexachlorocyclohexanes (HCHs), 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane
      (DDTs), dieldrin (aldrin), heptachlor-epoxide (heptachlor), and
      hexachlorobenzenes (HCBs) from foods, fish, fish products, meat, eggs, milk, and
      milk products were analyzed as major sources of these pesticides in the diet.
      Estimated daily intakes (EDIs) per person were 0.56 microgram for total HCH, 0.20
      microgram for gamma-HCH, 0.09 microgram for dieldrin, 1.42 micrograms for total
      DDT, and 0.15 microgram for HCB. Similarly, daily intakes of organophosphorus
      pesticides such as malathion and chlorpyrifosmethyl were estimated by analyzing
      wheat and wheat products as major contributing foods. EDIs of malathion and
      chlorpyrifos-methyl were 0.22 and 0.24 microgram, respectively. Daily intakes of
      total HCH, dieldrin, and total DDT in fiscal year 1992-1993 decreased 29, 44, and
      40%, respectively, but gamma-HCH intake increased 167%, in comparison with
      results of total diet studies for fiscal years 1980-1984. It was also shown that
      increase in gamma-HCH intake was due to recent increase in consumption of
      imported meat and meat products. Malathion intake did not change significantly.
      This method, which estimates EDIs based on concentrations of pollutants in main
      foods and statistical data of food consumption from the Japanese National
      Nutrition Survey, is considered to be sufficiently accurate for use as a
      simplified total diet study.

PMID- 7580331
TI  - U.S. Food and Drug Administration pesticide program: incidence/level monitoring
      of domestic and imported pears and tomatoes.
AB  - In 1992-1993, the U.S. Food and Drug Administration (FDA) conducted a
      statistically based study of pesticide residues in domestic and imported pears
      and tomatoes. For pears, 710 domestic and 949 imported samples were collected and
      analyzed; 79% of the domestic and 72% of the imported samples had detectable
      residues. Thiabendazole, a fungicide with postharvest uses, was found with
      greatest frequency in both groups of pears. Four domestic and 12 imported samples
      contained violative residues, mainly of pesticides for which there are no U.S.
      tolerances on pears. The statistically weighted (by shipment size) violation
      rates for domestic and imported pears were 1.0 and 0.9%, respectively. For
      tomatoes, 1219 domestic and 144 imported samples were collected and analyzed; 84%
      of the domestic and 91% of the imported samples had detectable residues.
      Methamidophos, an insecticide, had the greatest frequency of occurrence in both
      groups of tomatoes. Thirty-three domestic and 5 imported samples were violative,
      nearly all the result of acephate use, for which there is no U.S. tolerance on
      tomatoes. The statistically weighted violation rates for domestic and imported
      tomatoes were 1.9 and 7.0%, respectively. The statistically weighted violation
      rates calculated for domestic and imported pears and domestic tomatoes in this
      study were lower than those observed under FDA's regulatory monitoring in recent
      years. The violation rate for imported tomatoes was somewhat higher under
      statistical monitoring than under regulatory monitoring. The results of the
      statistically based study show that, as in regulatory monitoring, the levels of
      pesticide residues found are generally well below U.S. tolerances.

PMID- 7580333
TI  - Determination of ajmalicine in reserpine raw materials by liquid chromatography
      with fluorescence detection.
AB  - A method is presented for determination of ajmalicine in reserpine raw materials
      by liquid chromatography (LC) with fluorescence detection. The sample is
      dissolved in a very small volume of chloroform, and the resulting solution is
      diluted with methanol. The reference solution of ajmalicine is prepared directly
      in methanol. For LC, a 30 cm long normal-phase column is used. The mobile phase
      is methanol containing a small volume of an aqueous solution of 1-pentanesulfonic
      acid, sodium salt. Detection is by fluorescence with excitation at 280 nm and
      emission at 360 nm. In 3 samples, the ajmalicine contents ranged from 1.2 to
      1.9%.

PMID- 7580332
TI  - Daily intakes of tributyltin and triphenyltin compounds from meals.
AB  - Daily intakes of tributyltin (TBT) and triphenyltin (TPT) compounds from meals in
      Shiga Prefecture, Japan, were investigated by 2 methods. Daily intakes of TBT and
      TPT by the duplicate portion method were, respectively, 4.7 and 0.7 microgram in
      1991 and 2.2 and 0.7 microgram in 1992. Those by the market basket method were,
      respectively, 6.9 and 5.4 micrograms in 1991 and 6.7 and 1.3 micrograms in 1992.
      Daily intakes of TBT and TPT by the market basket method were higher than those
      by the duplicate portion method. These values were considerably lower than
      acceptable daily intakes of 80 micrograms/50 kg body weight specified by the
      Welfare Ministry of Japan for bis(tri-n-butyltin)oxide and of 25 micrograms/50 kg
      body weight specified by the Food and Agriculture Organization/World Health
      Organization for TPT.

PMID- 7580334
TI  - Determination of ephedrine, pseudoephedrine, and norephedrine in mixtures (bulk
      and dosage forms) by proton nuclear magnetic resonance spectroscopy.
AB  - A simple, specific, and accurate 1H nuclear magnetic resonance (NMR)
      spectroscopic method has been developed for quantitative determination of the
      Ephedra alkaloids (-)-ephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine,
      either singly or in mixtures with each other. Determination of individual
      alkaloids was carried out in D2O solution, with acetamide as internal standard.
      Although calculations were based on integrals for the C-CH3 protons, those for
      the N-CH3 and -CH-O- protons may also be useful, depending on the compound.
      Determination of diastereomeric cross-contamination of ephedrine and
      pseudoephedrine--or of the concentrations of these alkaloids in the presence or
      absence of (+/-)-norephedrine--was feasible by using the integrals for the -CH-O-
      protons after addition of a trace of DCl. Mean recoveries for ephedrine and
      pseudoephedrine from their respective synthetic mixtures with the internal
      standard (acet- amide) were > or = 99.9 +/- 0.6% (n = 10) and 99.6 +/- 0.8% (n =
      10) of the amount added. Recovery for pseudoephedrine from diastereomeric
      mixtures with ephedrine was > 99.4 +/- 0.7% (n = 10) of the amount added, with as
      little as 1.92% still being measurable. Mean recovery of (+/-)-norephedrine from
      mixtures with ephedrine and pseudoephedrine was > 99.7 +/- 2.5% (n = 4) of the
      amount added, with about 1% still being measurable. Application of the proposed
      NMR spectroscopic method to commercial dosage forms, including ephedrine sulfate
      injections and pseudoephedrine hydrochloride tablets, yielded assay results
      ranging from 97.8 to 100.2% (mean, 99.2%) and from 98.7 to 100.5% (mean, 99.7%)
      of declared, respectively.

PMID- 7580336
TI  - Determination of flunixin in milk by liquid chromatography with confirmation by
      gas chromatography/mass spectrometry and selected ion monitoring.
AB  - A liquid chromatographic (LC) method was developed for the determination of
      flunixin (FNX) in raw bovine milk. The milk was acidified and mixed with silica
      gel, and the mixture was packed into a chromatographic column. The column was
      defatted with water-saturated dichloromethane-hexane (30 + 70, v/v), and the
      analyte was eluted with EtOAc. The EtOAc extract was washed with water at pH 3.5,
      the water was discarded, and the EtOAc layer was then extracted with 0.1M NaOH.
      The aqueous layer was drained, passed through a primed C18 solid-phase extraction
      (SPE) column, and eluted with EtOAc. The EtOAc layer was dried under N2, taken up
      in a solution of MeOH-(5 mM tetrabutylammonium [TBA]-H2PO4 + 2 mM NaOH) (50 +
      50), sonicated, and filtered. FNX was determined by LC using a C18 column (ODS
      Hypersil), a mobile phase mixture of 58% A (MeOH) and 42% B (5 mM TBA-H2PO4 + 2
      mM NaOH), and a diode-array ultraviolet detector at 285 nm. FNX was determined in
      raw milk at 5 spiking levels (5, 10, 20, 40, and 80 ng drug/mL milk). Absolute
      recoveries ranged from 69.6 to 74.4%, and relative standard deviations ranged
      from 1.1 to 6.9%. The limit of quantitation was 1.7 ng drug/mL milk. A lactating
      cow was dosed intravenously (2.2 mg/kg) with flunixin meglumine (Banamine) to
      generate incurred milk residues. FNX residues ranged from 7.34 ng/mL at 16 h
      postdose to 1.74 ng/mL at 24 h postdose. Both levels were obtained with
      additional beta-glucuronidase treatment (almost no incurred drug was detected at
      these low levels without the enzyme treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580335
TI  - Proton nuclear magnetic resonance spectroscopic detection and determination of
      ethylene glycol dimethacrylate as a contaminant of methyl methacrylate raw
      material.
AB  - A simple, specific, and accurate proton nuclear magnetic resonance (1H NMR)
      spectroscopic method is presented for detection and assay of ethylene glycol
      dimethacrylate dimer as a contaminant of methyl methacrylate monomer. In addition
      to minimizing exposure of the analyst to the irritant and toxic methacrylic acid
      esters, the proposed method requires no sample preparation. Quantitations are
      based on integrals for signals of methylene protons of ethylene glycol
      dimethacrylate at 4.37 ppm and methyl protons of methyl methacrylate at 3.70 ppm.
      Analysis of 10 synthetic mixtures of the monomer with 1-11% of dimer yielded a
      dimer recovery of 100.5 +/- 2.05% (mean +/- standard deviation). Correspondence
      (correlation coefficient, r = 0.9999) between the amount of dimer added and the
      amount found was excellent. The proposed method measures as little as 1% of
      dimer.

PMID- 7580337
TI  - Practical screening procedures for sulfamethazine and N4-acetylsulfamethazine in
      milk at low parts-per-billion levels.
AB  - Relatively simple and inexpensive procedures for screening milk for
      sulfamethazine (SMZ) and one of its metabolites, N4-acetylsulfamethazine (ASMZ),
      are detailed. Both methods detect at the low parts-per-billion level and are
      suitable for both field and laboratory use. Milk is passed over Chromosorb 102,
      which adsorbs SMZ. The drug is eluted and purified by direct passage of the
      effluent over small beds of buffered anion-exchange resins and alumina and is
      finally isolated and detected colorimetrically. For ASMZ, the procedure is
      modified so that SMZ is removed in the purification steps. The isolated ASMZ is
      then hydrolyzed to SMZ for detection. Application of the methods 5 years apart
      (1988 and 1993) shows that SMZ is still being used but to a lesser extent in
      1993. Of over 250 samples screened in the 2 studies, only 2 were estimated to
      contain SMZ at 10 ppb, and the majority contained SMZ at 1 ppb. ASMZ was detected
      in a number of samples that were negative for SMZ.

PMID- 7580338
TI  - Gas chromatographic/mass spectrometric confirmation of leucomalachite green in
      catfish (Ictalurus punctatus) tissue.
AB  - A gas chromatographic/mass spectrometric (GC/MS) method was developed to confirm
      the presence of leucomalachite green (LMG), a metabolite of the triphenylmethane
      dye malachite green (MG), in catfish tissue. Residues were isolated according to
      a previously described liquid chromatographic (LC)/VIS spectrometric analysis of
      MG and LMG in fish. In our isolation procedure, analytes are extracted from
      tissue with acetonitrile-buffer, partitioned into CH2Cl2, and applied to neutral
      alumina and propylsulfonic acid solid-phase extraction cartridges. Before GC/MS
      analysis, extracts prepared for the LC determinative method are eluted from a
      cyano solid-phase extraction cartridge, extracted into organic solvent, and
      concentrated for GC/MS analysis. Selected ion monitoring was performed by using 5
      diagnostic ions (m/z 330, 329, 253, 210, and 165) of LMG. The method was
      validated by confirming LMG in tissue fortified with mixtures of MG and LMG (5
      and 10 ng/g each) and in tissue from fish that had been exposed to low levels of
      MG.

PMID- 7580339
TI  - Identification and measurement of beta-lactam antibiotic residues in milk:
      integration of screening kits with liquid chromatography.
AB  - A procedure for identifying and quantitating violative beta-lactams in milk is
      described. This procedure integrates beta-lactam residue detection kits with the
      multiresidue automated liquid chromatographic (LC) cleanup method developed in
      our laboratory. Spiked milk was deproteinized, extracted, and subjected to
      reversed-phase LC using a gradient program that concentrated the beta-lactams.
      Amoxicillin, ampicillin, cephapirin, ceftiofur, cloxacillin, and penicillin G
      were, thus, separated into 5 fractions that were subsequently tested for activity
      by using 4 kits. beta-lactams in the positive fractions were quantitated by
      analytical LC methods developed in our laboratory. The LC cleanup method
      separated beta-lactam antibiotics from each other and from interferences in the
      matrix and also concentrated the antibiotics, thus increasing the sensitivity of
      the kits to the beta-lactam antibiotics. The procedure facilitated the task of
      identifying and measuring the beta-lactam antibiotics that may be present in milk
      samples.

PMID- 7580340
TI  - Comparative and multilaboratory studies of two immunodiffusion method enrichment
      protocols and the AOAC/Bacteriological Analytical Manual culture method for
      detection of Salmonella in all foods.
AB  - The single enrichment immunodiffusion (1-step), the preenrichment and selective
      enrichment immunodiffusion (2-step), and the AOAC/Bacteriological Analytical
      Manual culture methods for Salmonella were evaluated for equivalence in 2
      separate studies, a comparative evaluation and a multilaboratory dilution study.
      In the comparative study, all 3 methods were performed on 10 food types. For 550
      samples, analyses resulted in 99.3 and 99.6% agreement between the culture method
      and the 1-step and 2-step methods, respectively. False negative rates were 0.9
      and 0.3% for 1-step and culture, and 0.0% and 0.6% for the 2-step and culture,
      respectively. Subsequently, 6 food types were included in a multilaboratory
      dilution-to-extinction study. A sequential dilution series of Salmonella in foods
      was analyzed by the 3 methods to determine their lower limits of detection for
      Salmonella. A total of 1185 samples analyzed resulted in 98.9% agreement between
      1-step and culture, and 99.7% agreement between 2-step and culture. False
      negative rates were 1.8 and 0.1% for 1-step and culture, and 0.4 and 0.1% for 2
      step and culture, respectively. During these evaluations, 1735 samples and
      controls representing 10 different naturally contaminated and inoculated foods
      were tested. The data indicate statistical equivalence of all 3 methods when
      analyzing all food types.

PMID- 7580341
TI  - Comparison of modified immunodiffusion and Bacteriological Analytical Manual
      (BAM) methods for detection of Salmonella in raw flesh and highly contaminated
      food types.
AB  - A wide variety of naturally contaminated and inoculated raw flesh and highly
      contaminated food types was analyzed by a modified immunodiffusion enrichment
      protocol and the Bacteriological Analytical Manual (BAM) method to determine the
      equivalence of these methods. This modification was developed by Agriculture
      Canada to allow addition of a high-temperature selective enrichment step in
      tetrathionate brilliant green broth at 42 degrees C while maintaining a 2-day
      total test time. Foods representing red meat, white meat, frog, and seafoods and
      one type of animal meal were evaluated. A total of 320 samples was tested,
      resulting in false negative rates of 5.2 and 3.5%, respectively, for the modified
      immunodiffusion and the BAM culture methods. The overall agreement rate was
      96.9%.

PMID- 7580342
TI  - Cryopreservation of bacterial vegetative cells used in antibiotic assay.
AB  - A long-term cryopreservation study of vegetative cells of Micrococcus lutea ATCC
      9341a, Micrococcus lutea ATCC 15957, and Staphylococcus epidermidis ATCC 12228
      cells, used in our antibiotic bioassay procedure, was conducted. The
      cryoprotective abilities of 1% methylcellulose solution and a 15% glycerol
      solution at -14 degrees C were determined. More organisms remained viable in 1%
      methylcellulose than in 15% glycerol. Overall survival of Staphylococcus
      epidermidis ATCC 12228 after 365 days was 1.5 logs lower than the other 2
      organisms. The sensitivity and the resistance of the preserved organisms to
      various antibiotics did not change. The methodology is simple and inexpensive,
      saves analytical time, and avoids risk of contamination and sudden loss of a well
      characterized culture.

PMID- 7580343
TI  - An overview of pathophysiological theories in Plasmodium falciparum cerebral
      malaria with the special reference to the role of cytokines.

PMID- 7580346
TI  - Reasons why the dockers lost their fitness for work--a retrospective survey.
AB  - Evaluation of the reasons for loss of capability for performing heavy and very
      heavy loading operations was based on retrospective population examinations
      carried out in two loading sites in ports. Enrolled in the study were 701 people,
      their working period in port over 5 years (mean 18.9 +/- 6.1 years). The age of
      the examined averaged 42.4 +/- 11.3 years. In course of 6 years 32.4% of this
      group changed their work due to structural changes in port, 67.6% due to loss of
      health qualifications. In the evaluation of health reasons predominant were
      diseases of the peripheral nervous system, of musculoskeletal system and of
      connective tissue (22.4%). Second as to the incidence were chronic diseases of
      the respiratory system and upper respiratory tracts (17.8%), in that 6% of
      allergies and 1.3% tuberculosis. Next were diseases of the circulatory system
      (13.3%), out of 3.8% were hypertension and 4.7% heart ischaemic disease. Last
      position was occupied by diseases of the stomach and duodenum (7.1%) and
      posttraumatic states of the muscular and osseous system (4.3%). Changing of the
      working post for health reasons up to 30th year of age occurred in 6.8%, up to
      40th year in 10.1% and to 50th year of life in 62.2% people examined. Change of
      the working post due to professional or educational promotion occurred chiefly
      below the age of 40.

PMID- 7580345
TI  - Evaluation of the circulatory system in a population of seamen and deep-sea
      fishermen based on the analysis of blood circulation by means of Wezler and
      Boeger's method.
AB  - 1,397 seamen and deep-sea fishermen were examined, their polycardiographic
      records were evaluated. Their mean age was 44.1 +/- 9.3 years, while the period
      of the service at sea averaged 22.8 +/- 7.1 years. Using Wezler and Boeger's
      method, physical analysis of the blood circulation was carried out. Carotid
      arteriograms were evaluated with Donzelot's method. Electrocardiograms were
      evaluated following Minnesota Code 1982. In 587 people (42.0%) pathological
      changes in the blood circulation were revealed. In 260 people (18.6%) ECG records
      were abnormal. In 112 people (8%) border hypertension was recorded and in 486
      people (13.3%) arterial hypertension was diagnosed. Abnormal speed of the central
      pulse wave, air chamber elasticity coefficient and peripheral resistance occurred
      in 35%, and abnormal carotid arteriograms were registered in 34.5% of the men
      examined. The data of the survey indicated that the risk of diseases of the
      circulatory system was high in the occupational group examined.

PMID- 7580344
TI  - Anticoagulant therapy in ischaemic heart disease in seafarers.

PMID- 7580348
TI  - State of the circulatory system and fitness for work at sea according to
      regulations binding in Poland (article for discussion).

PMID- 7580347
TI  - Guided fine needle absorption biopsy in the diagnosis of cysts in maritime
      workers.
AB  - Cysts in the organs of the abdominal cavity revealed in ultrasonographic
      examinations in patients with none or with unclear clinical symptoms cause
      diagnostic and fitness for work assessment problems. The aim of the study was to
      evaluate the usefulness of ultrasonography of cysts, combined with biochemical,
      bacteriological, cytological examinations and analysis of markers CEA and AFP of
      the fluid collected with fine needle aspiration biopsy (FAB). The study material
      examined were maritime workers who were submitted to these examinations for
      diagnostic purposes and/or previous to issue of certificate of health for work at
      sea. Examinations results provided support for usefulness of the method discussed
      in diagnosis and differentiation of inflammatory and neoplastic processes with
      simple cysts. This was crucial for final diagnosis, for decision about treatment
      and recognizing fitness for work at sea. It was concluded that the method FAB is
      safe both in hospital as well as in ambulatory conditions.

PMID- 7580349
TI  - Malaria as an occupational disease.
AB  - In Poland, cases of imported malaria are noted at present. In Polish citizens who
      work abroad, malaria is considered as an occupational disease. 95 cases of
      malaria in Polish citizens treated at the Clinic of the Institute of Maritime and
      Tropical Medicine in 1984-1993 were subjected to retrospective analysis,
      considering their occupational, epidemiological and clinical aspects as well as
      permanent sequelae of the disease. The most numerous groups among the patients
      examined were seafarers, fishermen, priests and missionaries. They were infected
      mostly in West Africa, during the first year of work. The majority of patients
      neglected chemoprophylaxis of malaria. In about 1/3 of patients, the resulting
      incapacity for work exceeded 1 month and more. In 7% of patients, 6 months after
      the treatment, permanent sequelae of the disease were observed: damage to the
      central nervous system, liver, kidneys and heart. The social and material costs
      of this invasive occupational disease were high. Malaria is an important health
      problem in Poles who work in endemic areas. Malaria prevention should be
      intensified.

PMID- 7580351
TI  - Occurrence of Borrelia spirochaetes in ticks (Acari, Ixodidae) collected in the
      forest areas in Olsztyn province (north central Poland).
AB  - In 1993, 2178 out of 3816 Ixodes ricinus and 45 out of 82 Dermacentor reticulatus
      collected from vegetation at 35 sites and removed from hunter-killed deer in
      Olsztyn province (N. C. Poland) were examined individually for the presence of
      Borrelia spirochaetes. Detection of spirochaetes was carried out by the routine
      indirect immunofluorescence assay (IFA) using polyclonal antibody anti-B.
      burgdorferi, strain 1 B 29. Borreliae, presumably B. burgdorferi, were evident in
      192 (11.5%) I. ricinus (nymphs and adults) collected from vegetation (n = 1666)
      and in 6 (1.2%) of those removed from hosts (n = 512). Among the first ones,
      infection rate in nymphs (7.5%) was 2.5 times lower than in adults (18.8%) but
      was similar in females (18.7%) and males (18.9%). The calculated minimal and
      maximal infection rates of ticks collected from different locations were 2.9% and
      35.7%, respectively. No spirochetes were observed in D. reticulatus tested.

PMID- 7580350
TI  - Distant health effects of using asbestos in shipyards and in co-operating plants.
AB  - A survey was conducted during a 15-years period (1981-1994) among a group of
      workers employed in shipyards and in cooperating plants, who were exposed to
      asbestos. In a group of 681 people surveyed a growing incidence of asbestosis of
      the lung was revealed: from 3.9% in 1981 to 17.9% in 1994. Since 1990, 19 persons
      have been found to have malignant neoplasms, in that number in 9 cases the
      location of neoplasm was evidently associated with the effects of the asbestos
      dust (3 mesotheliomas of the pleura and 6 bronchial cancers of the lungs). The
      smoking habit was probably a contributing factor in the occurrence of these
      diseases.

PMID- 7580352
TI  - The first isolation of Borrelia burgdorferi from Ixodes ricinus (Acari, Ixodidae)
      ticks in Poland.
AB  - Among ticks Ixodes ricinus collected in April 1994 in the forest near Fraknowo
      (Olsztyn province, N. C. Poland), 17 ticks were evaluated for Borrelia infection
      by cultivating in the BSK-H medium (Sigma). The ticks were examined in five pools
      -four of 3 females and one pool of 5 nymphs. Spirochaetes were cultured
      successfully only from one pool of females and identified as Borrelia burgdorferi
      with monoclonal antibodies: H 9724, H 5332, H 3TS and 11 G 1 by indirect
      immunofluorescence assay (IFA). This is the first reported isolate of B.
      burgdorferi from Ixodes ricinus in Poland.

PMID- 7580353
TI  - Chemical exposure of deck crew on product tankers loading the cargo with the
      hatches open.
AB  - Exposure of the deck crew to volatile hydrocarbon compounds and polycyclic
      aromatic hydrocarbon PAH compounds was observed and monitored on two Norwegian
      product tankers. The tankers were loading their cargo with the hatches open
      during the monitoring period. One of the tankers loaded gas oil. This type of
      cargo is not volatile, and very low concentrations of the monitored chemical PAH
      compounds were found on this tanker. The second tanker loaded gasoline. On this
      tanker high concentrations of hydrocarbon compounds were found; benzene was as
      high as 55 ppm, toluene was as high as 34 ppm, hydrocarbon compounds in the C5-C7
      range were as high as 570 ppm, n-hexane was as high as 25 ppm. The levels of PAH
      compounds were low. None of the seamen working on the deck did use respiratory
      protective equipment during the work. The exposure of the deck crew to volatile
      hydrocarbon compounds ought to be reduced on product tankers. Better routines
      concerning the use of respiratory protective equipment is an immediate action
      which ought to take place. Loading volatile cargo like gasoline with the hatches
      open should be avoided.

PMID- 7580354
TI  - Toxicity of combustion products of polymeric materials.

PMID- 7580355
TI  - Case of carbon monoxide poisoning treated with oxygen hyperbarism.
AB  - A case of heavy carbon monoxide poisoning is reported, with disorders in the
      central nervous system and circulatory disturbances (brain oedema), disfunction
      of the cardiac muscle and of platelet haemostasis). The level of
      carboxyhaemoglobin was over 45%. The patient was given hyperbaric treatment at
      0.15 MPa (2.5 ATA). On the first day of treatment, the time of stay in the
      hyperbaric chamber was 90 minutes. During the session the patient regained
      consciousness. Hyperbaric treatment was continued for 4 days more. At completion
      of the treatment, the disturbances in both the central nervous system and blood
      circulation recessed.

PMID- 7580356
TI  - Monoclonal antibodies against Vi antigen production and characterization.
AB  - As a result of fusion of in vitro immunized mouse splenocytes and myeloma Sp2/0
      cells, stable hybridomas secreting monoclonal antibodies against Vi antigen were
      obtained. The monoclonal antibodies were of IgM class. Reactivity of monoclonal
      antibodies to Vi antigen of different origin was tested. The reactivity was found
      to be independent of O-acetylation degree of Vi antigen.

PMID- 7580357
TI  - Transcultural aspects of schizophrenia: a comparative study in South Africa and
      in Namibia. A preliminary report.
AB  - Thirty six Coloured and Black patients with a clinical diagnosis of schizophrenia
      were evaluated by means of Present State Examination. The two groups were
      concordant by means of the 12 systems for the diagnosis of schizophrenia. This
      preliminary report has shown the difference in symptomatology of schizophrenia
      among the Coloureds of South Africa and the Blacks from Namibia. The differences
      are influenced by cultural and ethnical factors. The authors discuss the validity
      of methods employed in the study, especially language and intellectual capability
      as bias factors that may have influenced the final results.

PMID- 7580358
TI  - Antifibrinolytic therapy in cardiac surgery.
AB  - Bleeding remains an important complication after repeat and complicated cardiac
      surgery. Although aprotinin has recently been approved by the Food and Drug
      Administration for use as an antifibrinolytic agent, many surgeons continue to
      have concerns about its added cost and potential side effects. We review here the
      current state of antifibrinolytic therapy for excessive bleeding in
      cardiothoracic surgery and suggest the use of a single intravenous dose of 10 g
      of epsilon-aminocaproic acid immediately before cardiopulmonary bypass as a safe,
      inexpensive, and effective alternative to aprotinin. Further clinical and
      laboratory studies are needed to confirm or modify this protocol.

PMID- 7580361
TI  - Rotational ablation of discrete lesions in the coronary arteries is safe. A
      nonrandomized comparison with percutaneous transluminal coronary angioplasty.
AB  - Rotational ablation is receiving increasing attention as a new therapeutic
      intervention for coronary artery disease. In a nonrandomized study, we compared
      echocardiographic regional wall-motion scores of patients treated with rotational
      ablation with those of patients treated with percutaneous transluminal coronary
      angioplasty. We found that rotational ablation achieved angiographic results
      comparable to those of percutaneous transluminal coronary angioplasty, and was in
      fact associated with less myocardial ischemia. The reduction in ischemia observed
      in the ablation group might arise from shorter treatment times in those patients,
      from the use of nitroglycerin infusion in the ablation group, or from both
      factors.

PMID- 7580360
TI  - Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery.
      Prospective trial of 3 antifibrinolytic drugs.
AB  - Sixty consecutive patients undergoing elective open-heart surgery were
      prospectively enrolled in a study to compare the efficacy of 3 different
      antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous
      blood requirements in combination with blood-saving techniques and restrictive
      indications for blood transfusion. The patients were randomized to 1 of 4
      intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2)
      epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by
      infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes
      after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10
      hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia
      and 2 million KIU added to the extracorporeal circuit, followed by infusion of
      500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood
      drained from the operative field and the extracorporeal circuit after operation
      were used in all patients. Indications for blood transfusion were hypotension,
      tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with
      hemoglobin values < 7 g/dL. Compared with the blood loss in the control group,
      patients receiving aprotinin and epsilon-aminocaproic acid showed significantly
      less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/
      47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this
      trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin,
      344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p =
      0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid
      (p=0.002). Tranexamic acid did not have a statistically significant effect on
      blood loss. Homologous blood requirements were not significantly different among
      the groups; postoperative hematologic values and coagulation times were also
      comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown
      in the present study, the blood requirements were not significantly different
      from those that are found when transfusions are restricted, autotransfusions are
      used, and blood from the operative field and extracorporeal circuit is
      concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be
      indicated in routine cardiac surgery when other blood-saving techniques are
      adopted.

PMID- 7580362
TI  - Mitral regurgitation in patients with coronary artery disease and low left
      ventricular ejection fractions. How should it be treated?
AB  - In recent years, coronary artery bypass grafting has been extended to include
      patients with very low left ventricular ejection fractions. Should concomitant
      mitral valve regurgitation be corrected simultaneously? Between January 1990 and
      July 1994, 43 patients with preoperative left ventricular ejection fractions < or
      = 25% and echocardiographic evidence of concomitant mitral valve regurgitation
      (grade I, 18 patients; II, 19 patients; and III, 6 patients) underwent primary
      coronary artery bypass grafting. None of these patients underwent simultaneous
      mitral valve surgery. Twenty-four patients (56%) had pulmonary artery pressures >
      or = 40 mmHg (pulmonary hypertension). The mean preoperative left ventricular
      ejection fraction was 18.7% +/- 4.4% (range, 10% to 25%), and the mean pulmonary
      artery pressure was 45.6 +/- 15.8 mmHg. The average of number of grafts per
      patient was 4.5 +/- 1.5. Five patients underwent simultaneous repair of a left
      ventricular aneurysm. The hospital mortality rate was 4.7% (2/43). Transient low
      cardiac output occurred postoperatively in 13 patients (30%). Sixteen patients
      (37%) had no postoperative complications. The average follow-up of the 41
      hospital survivors was 6 months (range, 1 to 32 months). One patient died 8
      months after surgery for an overall mortality rate of 7%. Another 2 patients had
      graft occlusions that did not require reoperation. In the 40 surviving patients,
      follow-up echocardiography revealed that 37 patients (93%) had either no mitral
      valve regurgitation or only very mild mitral valve regurgitation (grade I). Three
      patients had grade II mitral valve regurgitation, but none required mitral valve
      surgery. The New York Heart Association functional class improved significantly
      in all hospital survivors (from 3.4 +/- 0.6 to 1.7 +/- 0.7; p > 0.001), and left
      ventricular ejection fractions rose from 19.0% +/- 4.6% to 42.0% +/- 8.3%.
      Coronary artery bypass grafting is possible in patients with very low left
      ventricular ejection fractions who present with 2- or 3-vessel disease,
      significant coronary artery stenoses (less than or equal 70%), and angina. The
      mortality rate is acceptable and morbidity is low. If there is no rupture of
      papillary muscle or chordae, concomitant ischemic mitral regurgitation (grades I
      through III) seems to return to normal after coronary artery bypass grafting and,
      therefore, does not need to be corrected surgically during the primary operation.

PMID- 7580359
TI  - Limiting excessive postoperative blood transfusion after cardiac procedures. A
      review.
AB  - Analysis of blood product use after cardiac operations reveals that a few
      patients (< or = 20%) consume the majority of blood products (> 80%). The risk
      factors that predispose a minority of patients to excessive blood use include
      patient-related factors, transfusion practices, drug-related causes, and
      procedure-related factors. Multivariate studies suggest that patient age and red
      blood cell volume are independent patient-related variables that predict
      excessive blood product transfusion after cardiac procedures. Other factors
      include preoperative aspirin ingestion, type of operation, over- or
      underutilization of heparin during cardiopulmonary bypass, failure to correct
      hypothermia after cardiopulmonary bypass, and physician overtransfusion. A survey
      of the currently available blood conservation techniques reveals 5 that stand out
      as reliable methods: 1) high-dose aprotinin therapy, 2) preoperative
      erythropoietin therapy when time permits adequate dosage before operation, 3)
      hemodilution by harvest of whole blood immediately before cardiopulmonary bypass,
      4) autologous predonation of blood, and 5) salvage of oxygenator blood after
      cardiopulmonary bypass. Other methods, such as the use of epsilon-aminocaproic
      acid or desmopressin, cell saving devices, reinfusion of shed mediastinal blood,
      and hemofiltration have been reported to be less reliable and may even be harmful
      in some high-risk patients. Consideration of the available data allows
      formulation of a 4-pronged plan for limiting excessive blood transfusion after
      surgery: 1) recognize the causes of excessive transfusion, including the
      importance of red blood cell volume, type of procedure being performed,
      preoperative aspirin ingestion, etc.; 2) establish a quality management program,
      including a survey of transfusion practices that emphasizes physician education
      and availability of real-time laboratory testing to guide transfusion therapy; 3)
      adopt a multimodal approach using institution-proven techniques; and 4)
      continually reassess blood product use and analyze the cost-benefits of blood
      conservation interventions.

PMID- 7580363
TI  - Surgical treatment of type A aortic dissections. Results with profound
      hypothermia and circulatory arrest.
AB  - Type A aortic dissection still presents an emergency situation in cardiac surgery
      that is associated with high morbidity and mortality rates. There has been a
      significant improvement in the surgical outcome since the introduction of deep
      hypothermia and circulatory arrest. In this study, we discuss our results after
      operative repair of ascending aortic dissections, using deep hypothermia and
      circulatory arrest. This study presents the results of 67 patients (43 men, 24
      women) from 18 through 81 years of age (mean, 54 years) who underwent surgery for
      type A dissecting aneurysm over a period of 4 years. Type A dissection (52 acute
      and 15 chronic cases) was due to Marfan syndrome in 12 patients, to
      atherosclerotic disease of the aorta in 27 patients, and to traumatic injury in 1
      patient. Hypertension as the only pathologic finding was observed in 27 patients.
      Deep hypothermia (confirmed by isoelectric electroencephalogram) and circulatory
      arrest were induced in all patients. Two patients died intraoperatively due to
      massive bleeding (intraoperative mortality, 3%). The 30-day mortality rate was
      30% (n = 20). Causes of perioperative deaths in order of frequency were multi
      organ failure (n = 11), myocardial infarction (n = 2), postoperative bleeding (n
      = 2), cerebrovascular insult (n = 2), and sepsis (n = 1). The mean intensive care
      unit stay of the surviving 47 patients (72%) was 8 days, followed by a mean of 21
      additional days in the hospital. Our experience with profound hypothermia and
      circulatory arrest, used in combination with coated grafts, supports our
      conviction that this is the method of choice for the treatment of type A
      dissecting aneurysm.

PMID- 7580365
TI  - Coronary artery bypass grafting in an achondroplastic dwarf.
AB  - To our knowledge, coronary bypass for complications of coronary artery disease in
      achondroplasia has not previously been described. Achondroplasia, in and of
      itself, is not a contraindication to coronary bypass. Although the anatomic
      reserve of saphenous vein is less in achondroplastic dwarfs than in people of
      normal stature, that vessel and the internal mammary artery can be harvested in
      routine fashion. A 60-year-old woman with several risk factors for coronary
      artery disease underwent successful bypass surgery, which included the use of
      both a saphenous vein and the left internal mammary artery.

PMID- 7580364
TI  - Transabdominal access to the thoracic aorta for aortofemoral bypass grafting.
AB  - When acute thrombosis of the abdominal aorta occurs in a comatose patient, direct
      examination of the intraabdominal organs becomes mandatory. Once a laparotomy has
      been performed, media calcinosis of the infrarenal aorta is a contraindication to
      its use as an inflow source. We describe a technique for exposing the thoracic
      aorta through the abdomen, which obviates the need for a thoracoabdominal
      incision in such critically ill patients.

PMID- 7580366
TI  - Removal of a giant cardiac fibroma from a 4-year-old child.
AB  - In an 8-month-old infant presenting with a systolic heart murmur, a cardiac tumor
      was diagnosed by means of 2-dimensional echocardiography, cardiac
      catheterization, and magnetic resonance imaging. In the following years, the
      child developed ventricular arrhythmias, which were controlled with
      antiarrhythmic drugs. The operation was undertaken when the boy was 4 years and 3
      months of age. A tumor of the interventricular septum measuring 45 x 13 x 25 mm
      was resected in toto. The defect in the ventricular septum was closed with a
      Dacron patch. The postoperative course was uneventful. Histologic examination
      classified the tumor as a fibroma.

PMID- 7580368
TI  - Subintimal hematoma of the aorta after deceleration injury.
AB  - Deceleration injuries of the aorta may occur without aortic disruption. We
      describe the case of a patient with a subintimal hematoma of the aorta that
      resolved within 48 hours. Serial arteriography confirmed the diagnosis and
      excluded aortic rupture. Thoracic exploration was not performed.

PMID- 7580369
TI  - Successful myocardial revascularization and neurologic recovery in a patient with
      prolonged refractory cardiac arrest and a chronically occluded left internal
      carotid artery.
AB  - Heretofore, the longest successfully treated cardiac arrest reported in the
      literature, secondary to myocardial ischemia, was one that required 45 minutes of
      cardiopulmonary resuscitation before coronary bypass surgery. We present a unique
      case of successful resuscitation after a cardiac arrest secondary to myocardial
      ischemia. The arrest lasted 78 minutes (30 minutes of closed cardiac massage and
      48 minutes of open cardiac massage). As soon as a perfusionist was available,
      cardiopulmonary bypass was initiated. After completion of the distal anastomosis
      and upon removal of the aortic cross clamp, the patient spontaneously recovered
      sinus rhythm for the 1st time since her cardiac arrest 2 hours and 10 minutes
      earlier. This 70-year-old woman, with a history of chronic occlusion of the left
      internal carotid artery, recovered fully, without evidence of neurologic or
      myocardial insult. We believe that vigorous closed and open cardiac massage,
      followed by cardiopulmonary bypass and the correction of myocardial ischemia,
      enabled this patient to survive a prolonged refractory cardiac arrest.

PMID- 7580370
TI  - Hypertrophic obstructive cardiomyopathy.

PMID- 7580367
TI  - Cardiac sarcoidosis. An unusual form of acute congestive cardiomyopathy.
AB  - We report the case of a previously healthy 45-year-old white man in whom
      sustained ventricular tachycardia and severe myocardial dysfunction were the only
      signs of cardiac sarcoidosis. Diagnosis was confirmed by endomyocardial biopsy,
      and the patient responded well to treatment with amiodarone and prednisone.

PMID- 7580371
TI  - Percutaneous biopsy of a pulmonary artery guided by computed tomography.

PMID- 7580372
TI  - Family medicine research.

PMID- 7580373
TI  - A French voice in family medicine research.

PMID- 7580374
TI  - Acknowledging a "pioneer" in family medicine.

PMID- 7580375
TI  - To test or refer: what are the benefits?

PMID- 7580376
TI  - Debating benzodiazepine use.

PMID- 7580377
TI  - Radiology rounds. Cerebellar astrocytoma.

PMID- 7580378
TI  - Dermacase. Gonococcemia.

PMID- 7580379
TI  - Each of the following statements about fibroadenoma of the breast and the long
      term risk of breast cancer is true, except...

PMID- 7580380
TI  - Who provides follow-up care for patients with early breast cancer?
AB  - OBJECTIVE: To assess how often family physicians are involved in posttreatment
      care of their stage I breast cancer patients and to identify factors associated
      with family physicians providing follow-up care. DESIGN: A retrospective cohort
      study with a 5-year follow up by chart review. PARTICIPANTS: All cases of breast
      cancer seen at the London Regional Cancer Centre between 1982 and 1987 were
      reviewed to identify 183 stage I cancer patients alive at 5 years. MAIN OUTCOME
      MEASURES: Whether a physician (other than an oncologist) was involved in the
      follow-up care of patients, and whether the physician was a family physician or a
      surgeon. RESULTS: Follow-up care during the 5-year postoperative period was
      provided in most cases by oncologists alone (66.7%); family physicians and
      surgeons were involved in 17.5% and 15.8% of cases, respectively. Surgeons became
      involved in follow-up care much earlier (12 months) than family physicians did
      (23 months) (P = 0.01) and were more likely to provide care for patients who
      received radiation treatment (P = 0.04) and for patients who lived in London (P =
      0.004). Most malignant breast lesions (77.5%) were discovered by patients
      themselves (P = 0.0001). CONCLUSIONS: Currently, family physicians are
      infrequently involved in follow-up care of their patients with early breast
      cancer.

PMID- 7580382
TI  - [Utilization of computerized classification system of primary care: three years
      of experience].
AB  - OBJECTIVE: To develop and implement a computerized version of the International
      Classification of Primary Care. To create a data bank and to conduct a
      descriptive study of our clinic's clientele. DESIGN: Testing a software program
      and creating a data bank. SETTING: Family Medicine Unit at Enfant-Jesus Hospital,
      Quebec City. PARTICIPANTS: All Family Medicine Unit doctors and patients seen
      between July 1, 1990, and June 30, 1993. MAIN OUTCOME MEASURE: Description of our
      clientele's health problems using the ICPC. RESULTS: During the study, 48,415
      diagnostic codes for 33,033 visits were entered into the bank. For close to 50%
      of these visits, two or more health problems were coded. There was good
      correlation between the description of our clientele and descriptions in other
      studies in the literature. CONCLUSION: This article describes the development of
      a data bank in a family medicine unit using a software program based on the ICPC.
      Our 3-year experiment demonstrated that the method works well in family
      physicians' daily practice. A descriptive study of our clientele is presented, as
      well as a few examples of the many applications of such a data bank.

PMID- 7580381
TI  - Community resources for psychiatric and psychosocial problems. Family physicians'
      referral patterns in urban Ontario.
AB  - OBJECTIVE: To document the number and pattern of psychiatric and psychosocial
      referrals to community resources by family physicians (FPs) and to determine
      whether referral practices correlate with physician variables. DESIGN: Cross
      sectional survey of referrals by FPs to 34 key psychiatric and psychosocial
      community resources identified by a panel of FPs, psychiatric social workers,
      psychiatric nurses, public health nurses, and the local community information
      service. SETTING: Regional municipality of 434,000 persons in Ontario.
      PARTICIPANTS: Twenty-seven of 34 (79%) community agencies identified 261 FPs who
      made 4487 referrals to participating agencies (range 0 to 65, median 15, mean
      17.19 +/- 13.42). MAIN OUTCOME MEASURES: Number of referrals to all agencies;
      variables, such as physician sex, school of graduation, year of graduation, and
      certificate status in the College of Family Physicians of Canada, related to
      referral patterns. RESULTS: Referrals to outpatient psychiatric clinics, support
      services, and general counseling services accounted for 96% of all referrals.
      Physicians' average annual referral profile was as follows: 8.6 patients to a
      support service, 6.3 to an outpatient psychiatric service, 1.6 to a counseling
      service, and 0.46 to a substance abuse service. Referral profiles of individual
      physicians varied greatly. Female FPs made fewer referrals than male FPs to
      support services, but both made similar numbers of referrals to psychiatric,
      counseling, and substance abuse services. The more recent the year of graduation,
      the greater the number of referrals to psychiatric (r = 0.158, P = 0.0107) and
      counseling services (r = 0.137, P = 0.0272) and the higher the fraction of
      referrals to psychiatric services (r = 0.286, P = 0.0001). CONCLUSIONS: Family
      physicians in Hamilton-Wentworth made few referrals to psychiatric and
      psychosocial services. Only physician sex and year of graduation correlated
      significantly with numbers of referrals made. Recent graduates of both sexes made
      significantly more referrals to psychiatric clinics and counseling services than
      their older colleagues.

PMID- 7580383
TI  - Structured oral interview. One way to identify family physicians' educational
      needs.
AB  - OBJECTIVE: To design and test a structured oral interview that would elicit
      information on the educational needs of physicians in order to help them plan
      individualized continuing education. DESIGN: Seven different sets of problems
      were prepared, each including 40 cases, of which 26 are common. Each pilot test
      candidate was interviewed by two physician-interviewers during a 1-day session.
      After each answer, candidates were told the predetermined correct answer.
      PARTICIPANTS: Six candidates were selected at random from among Montreal
      physicians aged 50 and older with no hospital privileges. All had to have no
      history of professional complaints or prosecution and to be unknown to the
      interviewers. MAIN OUTCOME MEASURES: Inter-rater reliability and perceived
      difficulty of the cases. RESULTS: Candidates rated the interview process and
      cases used pertinent, credible, and not too difficult. Candidates' performance
      level was about 50%. Agreement between interviewers averaged 91.2%. CONCLUSIONS:
      A structured oral interview appears to be a credible instrument for helping
      determine practising physicians' deficiencies in clinical knowledge and
      reasoning.

PMID- 7580384
TI  - Comprehensiveness and bias in reporting clinical trials. Study of reviews of
      pneumococcal vaccine effectiveness.
AB  - PURPOSE: To assess the extent to which relevant controlled clinical trials are
      cited and summarized in review articles, and to determine whether citation of
      relevant clinical trails is biased as to study results. DATA SOURCES: Articles
      were identified by searching MEDLINE and EMBASE databases. STUDY SELECTION:
      Review articles published between 1986 and 1988 on the clinical effectiveness of
      pneumococcal vaccine. DATA EXTRACTION: Proportion of relevant clinical trials
      cited and whether citation is biased by study results. DATA SYNTHESIS: The
      proportion of relevant primary studies cited per review article ranged from 0% to
      36% (mean 9%). The number of trials cited per review ranged from zero to six
      (mean 1.2). In nine of 17 reviews, no clinical trials were cited. Study
      populations and outcome(s) were specified and results presented quantitatively
      for 0 to 27% of relevant trials per review (mean 6%). Unsupportive trials were
      almost twice as likely to be cited as supportive trials. CONCLUSIONS: Reporting
      of the results of relevant clinical trials in reviews of pneumococcal vaccine
      effectiveness is incomplete. Our findings suggest a need for greater scientific
      rigour in preparing, reviewing, and editing review articles.

PMID- 7580385
TI  - Do pharmaceutical representatives misuse their drug samples?
AB  - OBJECTIVE: To determine the extent to which pharmaceutical representatives misuse
      their samples. DESIGN: Voluntary questionnaire survey. SETTING: A family practice
      office. PARTICIPANTS: Pharmaceutical representatives visiting the office during a
      3-month period. MAIN OUTCOME MEASURES: Number of surveyed representatives who
      self-medicated, provided samples of prescription drugs to nonphysicians, or
      exchanged drugs with other representatives; classes of prescription drugs most
      commonly used; and beneficiaries. RESULTS: Of the 27 representatives surveyed, 16
      (59.2%) have provided prescription drug samples to individuals other than
      physicians. Thirteen (48.1%) either self-medicated or provided samples to friends
      or relatives. Seven (25.9%) have exchanged drug samples with other
      representatives. Eleven (40.7%) of the 27 surveyed had not sampled prescription
      drugs themselves, given them to others, or exchanged drugs with other
      representatives. The most commonly sampled drugs were nonsteroidal anti
      inflammatory drugs. Drug samples were most often given to friends and spouses.
      CONCLUSION: Self-medication and giving samples to nonphysicians were practised by
      almost 60% of surveyed representatives. Representatives usually caution
      recipients, however, and there are very few complications. Drugs with potential
      for abuse or dependence and cardiovascular medications were rarely used.

PMID- 7580387
TI  - Developing a family medicine presence on the Internet.

PMID- 7580386
TI  - Patient consent to observation. Responses to requests for written consent in an
      academic family practice unit.
AB  - OBJECTIVE: To examine patient rates of consent to observation and response to
      being asked for written consent. DESIGN: Patients were asked to provide written
      consent for a supervising physician to observe a resident performing a physical
      examination, or for both direct observation and videotaping of the visit. After
      the visit, all patients were interviewed, and patients who had given written
      consent completed a questionnaire. SETTING: The family practice unit at a
      teaching hospital affiliated with the University of Toronto. PARTICIPANTS: A
      representative sample of new and returning patients. MAIN OUTCOME MEASURES:
      Patient consent to observation or videotaping. RESULTS: Most patients (92.2%)
      agreed to be observed. Of those asked only for consent to observe, 97.3% agreed.
      Of those asked for consent to observe and videotape, 85.2% agreed. When
      specifically asked, 22% of patients who agreed to observation expressed concerns.
      CONCLUSION: We must devise clear policies and procedures for obtaining patient
      consent that are both sensitive to patients' concerns and administratively
      effective.

PMID- 7580388
TI  - Section of researchers. College of Family Physicians of Canada.

PMID- 7580389
TI  - New and experimental therapies for treating graft-versus-host disease.

PMID- 7580390
TI  - Amyloidosis.
AB  - Amyloidosis is the generic term for a heterogeneous group of disorders
      characterised by the common finding of amyloid deposition. The various acquired
      and hereditary syndromes are classified according to the identity of the
      respective amyloid fibril sub-unit protein. Systemic amyloidosis and some local
      forms are progressive diseases that are frequently fatal. The diagnosis of
      systemic amyloidosis is only occasionally suspected on clinical grounds alone,
      and is more often considered when an associated disorder such as a chronic
      inflammatory disease or monoclonal gammopathy is present. No blood test is
      diagnostic of amyloidosis but routine haematological and biochemical
      investigations have important roles in defining the underlying metabolic
      disturbance and evaluating function of affected organs. The diagnosis can only be
      confirmed by demonstrating the presence of tissue amyloid deposits. Traditionally
      this required histology but the recent introduction of labelled serum amyloid P
      component scintigraphy is a specific alternative that provides a quantitative
      macroscopic whole body survey of amyloid deposits. No treatment specifically
      causes the resolution of amyloid but therapy which reduces the supply of amyloid
      fibril precursor proteins can improve survival and preserve organ function. Major
      regression of amyloid occurs in at least a proportion of such cases suggesting
      that clinical improvement reflects mobilisation of amyloid.

PMID- 7580391
TI  - Fetal and neonatal thrombocytopenia.
AB  - Thrombocytopenia is defined as platelet count less than 150,000 plat/mm3.
      Etiologic factors involved include immunological (NAIT and ITP), fetal infectious
      disease, chromosomal and nonchromosomal, and miscellaneous causes. While the
      understanding of fetal thrombocytopenia is driven by reason to do fetal blood
      sampling, discovery of neonatal thrombocytopenia is driven by blood counts
      performed because of the risk of infections. The most serious consequence of
      thrombocytopenia in the fetus/neonate is intracranial hemorrhage which can occur
      in utero as early as 18 weeks gestation. The key factor in perinatal prevention
      of intracranial hemorrhage is early diagnosis and treatment, possibly in utero.
      Cordocentesis under direct ultrasound guidance and platelet transfusions have
      played a major role in the management of fetal/neonatal thrombocytopenia. Ongoing
      studies and high resolution ultrasound will continue to explore and hopefully
      clarify fetal and neonatal thrombocytopenia and facilitate recognition of primary
      and secondary thrombocytopenias.

PMID- 7580392
TI  - The rarer inherited coagulation disorders: a review.
AB  - Of the inherited bleeding disorders, haemophilia A, haemophilia B and von
      Willebrand's disease make up together well over 80% of those registered with the
      UK Haemophilia Centre Directors. The common simple screening tests of coagulation
      may overlook some of the more rare disorders and it is clearly important that
      such uncommon bleeding disorders are excluded during the course of the
      investigation of children considered to be suffering from non-accidental injury.
      In this article, some of the rare inherited bleeding disorders are considered,
      including haemophilia B Leyden, deficiencies of factors VII, X, XI, and XII, as
      well as inherited defects of platelet number and function. Presenting features
      are described and recommendations regarding appropriate therapy given. In order
      to assist in advancing understanding of the biochemistry and molecular genetics
      of these disorders, clinicians are encouraged to share clinical information and,
      where appropriate, blood samples with interested research workers.

PMID- 7580394
TI  - Meta-analyses and overviews of randomised trials.
AB  - The number of meta-analyses or overviews appearing in the literature is rapidly
      increasing. Because of the problems inherent in non-randomised studies, which are
      not diminished by using meta-analysis techniques, this paper only refers to meta
      analyses of randomised trials. Examples are given of the value of meta-analyses
      of randomised trials in many different circumstances and the different methods
      that have been used are discussed. The most reliable type of meta-analysis uses
      individual patient data and includes all trials fitting the pre-defined criteria,
      published and unpublished. As with a single randomised trial, large numbers of
      randomised patients are needed to give reliable results. Well-conducted meta
      analyses or overviews are the best method of summarising all available unbiased
      evidence on the relative effects of treatments.

PMID- 7580393
TI  - The role of cytokines in blood transfusion reactions.
AB  - Recent advance in the understanding of the mechanism of hemolytic transfusion
      reactions results from the investigation of cytokine generation in in vitro
      models of incompatible red blood cell transfusion. Cytokines with pyrogenic and
      pro-inflammatory activities as well as cytokines with activating properties for
      granulocytes, monocytes and endothelial cells are produced in both
      'intravascular' and 'extravascular' types of hemolytic reactions. It has also
      been demonstrated that cytokines are generated and accumulated in blood
      components such as platelet concentrates, during storage. A large part of febrile
      transfusion reactions results from transfusion of stored platelet concentrates
      containing high cytokine levels and not from antigen-antibody reactions.
      Prestorage removal of white blood cells, which generate cytokines during storage,
      from platelet concentrates reduces strongly the reaction incidence and should be
      standard practice.

PMID- 7580395
TI  - Mechanism and management of treatment-related gonadal failure in recipients of
      high dose chemoradiotherapy.
AB  - For the last two decades, the use of bone marrow transplantation for leukaemia,
      and most recently for lymphomas and other cancers, has increased dramatically and
      all of the systemic chemotherapy or radiotherapy used in these patients has a
      potential for causing infertility. This review describes the normal reproductive
      function of relevance to patients at risk of chemotherapy- or radiotherapy
      induced infertility. The mechanism by which fertility may be affected by these
      agents is also described and therapeutic strategies for reducing or preventing
      these problems are outlined. The treatment of men and women who are infertile
      after chemotherapy or radiotherapy is addressed, as are the ethical and legal
      aspects of assisted fertilization.

PMID- 7580396
TI  - Effects of temporal versus temporal plus extra-temporal lobe epilepsies on
      hippocampal ERPs: physiopathological implications for recognition memory studies
      in humans.
AB  - The present experiment was designed to investigate the incidence of temporal and
      extra-temporal epileptogenic lesions on hippocampal activity related to
      recognition memory. Hippocampal event-related potentials (ERPs) were recorded
      during a recognition memory task for pictures in patients with unilateral
      temporal lobe epilepsy and in patients with combined temporal and extra-temporal
      (frontal or parietal) epileptogenic foci. In the first group, the comparison
      between correctly recognized pictures and new distractors revealed that the usual
      ERP (N400/P600) 'old/new' effects were not dramatically affected by the presence
      of a temporal epileptogenic lesion. In contrast, these effects were absent in
      multifocal epilepsy patients, indicating that frontal and parietal brain regions
      play a part in the modulation of hippocampal ERP and related memory processing.
      These results suggest that ERP 'old/new' effects are dependent on interactions
      between frontal, parietal and medial temporal structures. Together with the
      results of other recent studies devoted to locating the neural sources of N400
      and P600, the present findings provide physiopathological evidence that ERP
      'old/new' effects are subtended by distributed yet interconnected brain regions
      that are known to play an important role in recognition memory processing.

PMID- 7580397
TI  - Learning to ignore: psychophysics and computational modeling of fast learning of
      direction in noisy motion stimuli.
AB  - The effects of practice on the discrimination of direction of motion in briefly
      presented noisy dynamic random dot patterns are investigated in several forced
      choice psychophysical tasks. We found that the percentage of correct responses on
      any specific task increases linearly with repetition of trials within roughly 200
      trials from about chance to a performance of 90% or better. The level of
      performance remained constant or improved over several days, and in most
      instances it did not transfer when stimulus parameters changed. We used a
      modified Radial Basis Function (RBF) representation to model the psychophysical
      tasks. The performance of the model is functionally similar to the psychophysical
      results. We propose a Hebbian learning algorithm which deactivates the inputs
      from neurons responding to motion noise in the stimulus. Our computational model
      suggests that to solve this task in biological systems, neurons (perhaps in MT)
      improve their performance by 'learning to ignore' noise in the image.

PMID- 7580398
TI  - Whole head mapping of magnetic fields following painful electric finger shock.
AB  - Painful intracutaneous electric finger shock was delivered to the fifth digit of
      the non-dominant hand of five healthy volunteers. Whole head evoked magnetic
      field maps were collected and cortical localizations were calculated using local
      sphere equivalent current dipole fits. MRI scans were used to identify the
      anatomical structures where magnetic field sources were located. Anatomically,
      sources were identified bilaterally in the primary somatosensory region and SII
      Insula regions. Additionally, frontal operculum sources were observed
      contralaterally in two subjects. Temporally, an initial contralateral SI
      activation at 40-60 ms was followed by several SII-Insula responses over the next
      several hundred milliseconds (ms). These SII-Insula responses were often
      interspersed with additional activations of the SI region. These later responses
      were observed in both hemispheres.

PMID- 7580399
TI  - Event-related potentials in patients with cerebellar degeneration:
      electrophysiological evidence for cognitive impairment.
AB  - We measured event-related potentials and reaction times during semantic
      discrimination tasks in 8 patients with cerebellar degeneration and in 10 normal
      subjects. The NA, N2 and P3 latencies of patients were significantly longer in
      patients, whereas N1 and P2 latencies did not differ between both groups. There
      was also no difference in the simple and GO/NOGO reaction times. These results
      suggest that these patients' impairment in cognitive information processing arose
      from a difficulty in pattern recognition of the stimuli represented by the NA
      component. These data also support the notion that the cerebellum plays a role in
      cognitive information processing.

PMID- 7580400
TI  - Novelty seeking behavior in the rat is dependent upon the integrity of the
      noradrenergic system.
AB  - These experiments were designed to investigate the role of the noradrenergic
      system in promoting investigation of novelty in rats. Behavior was monitored in a
      hole board equipped with photoelectric cells strategically placed so that
      locomotor activity, rearing and investigation of each of the holes could be
      quantified independently. Specially designed computer software permitted
      recording of the sequence and cumulative duration of the visits to specific holes
      throughout the session. Dose-response curves of the sedative effect of the alpha
      2 adrenergic receptor agonist clonidine were established, a sedative effect being
      defined as a decrease in overall horizontal displacements, rearings and hole
      visits. After a one week interval, the rats were rerun in the holeboard, with
      novel objects placed in four of the nine holes. Previous experiments had shown
      that rats spend significantly more time investigating holes containing objects
      than empty holes in this apparatus and this was replicated here. Doses of
      clonidine which were below threshold for inducing any sedative effect (10
      micrograms/kg) totally eliminated preference for holes with objects while having
      no effect on total time investigating the holes. A subsequent experiment showed
      that the beta receptor antagonist propranolol (10 mg/kg) produced a similar
      effect. These results suggest that the noradrenergic system is implicated in
      stimulus seeking behavior and the post-synaptic beta receptors are involved in
      mediating the behavior.

PMID- 7580401
TI  - Luminance and spatial attention effects on early visual processing.
AB  - Event-related potentials (ERPs) were recorded from healthy subjects in response
      to unilaterally flashed high and low luminance bar stimuli presented randomly to
      left and right field locations. Their task was to covertly and selectively attend
      to either the left or right stimulus locations (separate blocks) in order to
      detect infrequent shorter target bars of either luminance. Independent of
      attention, higher stimulus luminance resulted in higher ERP amplitudes for the
      posterior N95 (80-110 ms), occipital P1 (110-140 ms), and parietal N1 (130-180
      ms). Brighter stimuli also resulted in shorter peak latency for the occipital N1
      component (135-220 ms); this effect was not observed for the N1 components over
      parietal, central or frontal regions. Significant attention-related amplitude
      modulations were obtained for the occipital P1, occipital, parietal and central
      N1, the occipital and parietal P2, and the parietal N2 components; these
      components were larger to stimuli at the attended location. In contrast to the
      relatively short latencies of both spatial attention and luminance effects, the
      first interaction between luminance and spatial attention effects was observed
      for the P3 component to the target stimuli (350-750 ms). This suggests that
      interactions of spatial attention and stimulus luminance previously reported for
      reaction time measures may not reflect the earliest stages of sensory/perceptual
      processing. Differences in the way in which luminance and attention affected the
      occipital P1, occipital N1 and parietal N1 components suggest dissociations among
      these ERPs in the mechanisms of visual and attentional processing they
      reflect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580402
TI  - Cortical activation with sound stimulation in cochlear implant users demonstrated
      by positron emission tomography.
AB  - Six postlingually deaf patients using multi-channel cochlear implants were
      examined by positron emission tomography (PET) using 15O-labeled water. Changes
      in regional cerebral blood flow (rCBF) were measured during different sound
      stimuli. The stimulation paradigms employed consisted of two sets of three
      different conditions; (1) no sound stimulation with the speech processor of the
      cochlear implant system switched off, (2) hearing white noise and (3) hearing
      sequential Japanese sentences. In the primary auditory area, the mean rCBF
      increase during noise stimulation was significantly greater on the side
      contralateral to the implant than on the ipsilateral side. Speech stimulation
      caused significantly greater rCBF increase compared with noise stimulation in the
      left immediate auditory association area (P < 0.01), the bilateral auditory
      association areas (P < 0.01), the posterior part of the bilateral inferior
      frontal gyri; the Broca's area (P < 0.01) and its right hemisphere homologue (P <
      0.05). Activation of cortices related to verbal and non-verbal sound recognition
      was clearly demonstrated in the current subjects probably because complete
      silence was attained in the control condition.

PMID- 7580403
TI  - Region-dependent asymmetrical or symmetrical variations in the oxygenation and
      hemodynamics of the brain due to different mental stimuli.
AB  - The present paper demonstrates region-dependent variations in the oxygenation and
      hemodynamics of the brain hemispheres due to three different types of mental
      stimulation. The variations were observed with a four-channel optical imaging
      system using tissue-transparent near-infrared light and described changes from
      baseline of both the hemoglobin oxygenation state and blood volume during three
      kinds of psychological or mental tasks. During the mirror drawing task, a
      lateralized hemisphere response (the dominant hemisphere response pattern) was
      observed in 57% of 14 right handed volunteers in the frontal region (Brodmann's
      area 10), while in the temporal region (area 38), 80% showed the bilateral
      response pattern. A large majority of the subjects showed the bilateral response
      pattern in the frontal and temporal regions while calculating. A smaller majority
      showed this while looking at anatomical charts, though 30% did not show any
      response at all in the temporal region. This showed that there were region
      dependent asymmetrical or symmetrical variations of the oxygen delivery-oxygen
      utilization relationship due to different types of mental stimuli.

PMID- 7580404
TI  - [Varying sensitivity to acyclovir of different years' clinical isolates of herpes
      simplex virus].
AB  - The population of types I and 2 herpes simplex viruses (HSV) to be studied
      consisted mainly of Acyclovir-sensitive strains. In some cases Acyclovir
      resistant HSV strains were detected. The phenotypic profile of the Acyclovir
      resistant strains were shown to have low reproduction rates in tissue cultures.
      Their antigenic character was similar to that of reference strains. Several
      phenotypic variants concurrently isolated from the same patient differ in their
      reproductive properties, antigenic characteristics, and sensitivity to Acyclovir.
      It is expedient to examine HSV isolates from patients for their sensitivity to
      chemicals used in clinical practice. This will allow patients with herpes
      infection to be treated on an individual basis.

PMID- 7580405
TI  - [Effects of influenza virus proteins on immunocompetent cells of the host].
AB  - Only 2 influenza viral proteins--HA and M--have been shown to be active against
      host T cells, M protein being more active than HA in some tests when interacted
      with CD4 receptor. M protein stimulated the expression of CD25 receptors and the
      proliferation of lymphocytes; the activated production of alpha-tumor necrosis
      factor was undetectable when exposed to virus proteins.

PMID- 7580406
TI  - [Comparative study of genomes of present-day influenza A and B viruses].
AB  - The electrophoretic mobility of RNA fragments was used to study epidemic
      influenza viruses A and B as compared with the reference strains and virological
      findings. Among those tested, there was a further drift involving both the genes
      coding glycosylated proteins and internal and non-structural proteins. The
      analysis of atypical isolates showed their reassortant nature.

PMID- 7580408
TI  - [Clinical and x-ray features of lung lesions in influenza uncomplicated and
      complicated by pneumonia].
AB  - Clinical and X-ray features of pulmonary lesions were studied in 858 inpatients
      with pneumonia-complicated and uncomplicated influenza. This showed it possible
      to establish a clinical and X-ray diagnosis of viral pulmonary lesions in the
      early period of infection. There was a correlation between influenza toxicosis
      and the magnitude of lung X-ray changes. There were variations in the X-ray
      pattern of secondary pneumonia in relation to the time of their occurrence.

PMID- 7580407
TI  - [Elaboration of the polymerase chain reaction system for subtype specific
      differentiation of influenza A virus strains].
AB  - New subtype specific primers for hemagglutinin (H1, H2, H3) of influenza A
      viruses were selected. The specificity of the primers' performance was tested in
      a model experiment which used cDNA synthesized on the vRNA from the collection of
      influenza A viruses (H1, H2, H3 subtypes) as templates. The sensibility of the
      PCR system was determined on DNA plasmids- and RNA templates (with preliminary
      reverse transcription) and amounted to 10(2) and 10(5)-10(6) virion particles,
      respectively.

PMID- 7580409
TI  - [Class I histocompatibility antigens as markers of human susceptibility to
      influenza A viruses].
AB  - The results of many years' studies of HLA-phenotypes in human beings with various
      susceptibility to influenza infection are presented. Some histocompatibility
      class I antigens are revealed to correlate moderately with the risk of
      reinfection and the recurrent course of influenza, as well as with the severity
      of pulmonary complications and with the inclination of a macroorganism to the
      latent carriage of viral proteins. The specific features of a humoral immune
      response to vaccination with attenuated influenza viruses in human beings with
      HLA-B8 are demonstrated. The authors indicate that there is a trend towards less
      pronounced manifestations of influenza infection in individuals with antigen
      markers A9, B40, characteristic of a Mongoloid population, which might be related
      to the origin of influenza viruses.

PMID- 7580410
TI  - [Characteristics of dynamics of influenza epidemics and trends of change].
AB  - Long-term epidemiological data on 60 reference bases (cities) of the Regional
      Influenza and Acute Respiratory Disease Center (for the former USSR) are
      analyzed. Trends in developing an epidemiological process are defined. It is
      shown that the rate influenza A epidemics has been recently declined, its
      morbidity is decreasing among adults and increasing among children: influenza A
      epidemics has recently shown mainly its endogenous spread. Influenza B epidemics
      have become more intensive, but in the past years influenza B morbidity has been
      also stable.

PMID- 7580411
TI  - [Significance of the functional activity of antibodies in influenza immunity].
AB  - A simple and inexpensive test for mass examination of the functional activity of
      serum antibodies was developed. The test is based on a kinetic serologic reaction
      that reflects the time course of changes in antibody titers depending on the time
      of contact of the tested material with antigen. The curves of serum kinetic
      titration were processed on a computer by the special programme. As a result, an
      integral factor, an antibody functional activity index (AFAI) was calculated for
      each serum sample under study. The titers and AFAI were determined in more than
      2,000 healthy persons, patients with influenza A and B, and those immunized with
      different influenza vaccines. The persons having similar antibody titers were
      demonstrated to greatly differ in AFAI. The functional activity of antibodies is
      a more precise marker of protection from influenza than the routine quantitative
      characteristics of antibodies, i.e. titers. The high baseline AFAI decreased the
      severity of influenza infection. Live influenza vaccines stimulated the
      production of antibodies having higher AFAI than inactivated ones. The live
      influenza strains (candidates for vaccine ones) significantly differed in their
      ability to stimulate the production of antibodies having a high functional
      activity.

PMID- 7580412
TI  - [The origin of resistance to chemicals of naturally occurring isolates of
      influenza A virus].
AB  - The mechanisms responsible for the formation of resistance of influenza A virus
      isolates during the natural circulation of the influenza viruses in the
      environment were studied. The influenza viruses H1N1 and H3N2 resistant to
      remantadine, adapromine, and deitiforine have been isolated in the USSR and
      Mongolia since 1982. The majority of natural resistant isolates appeared to be
      atypical both in antigenic properties and genomic structure as compared to the
      isolates prevalent in the common epidemic process. The nucleotide sequences of
      the M2 gene of some resistant strains and virus A/PR8/34 used in our country as
      an attenuation donor for preparation of killed recombinant vaccines. The
      electrophoretic mobility of genomic RNA of two resistant isolates is similar to
      that of the vaccine strain X-54 based on the virus A/PR/8/34. In this connection,
      the appearance of resistant strains in the environment may be due not only to
      spontaneous mutagenesis or selective drug actions, but also to the involvement
      into the circulation of vaccinal strains.

PMID- 7580413
TI  - [Mathematical modeling of the spread of influenza virus strains resistant to
      chemicals].

PMID- 7580414
TI  - [Immune replacement therapy in RS infection].
AB  - Respiratory syncytial (RS) virus is the main cause of severe respiratory
      infections in newborns and infants during the first year of life. In the recent
      years, search is under way for chemo- and immune replacement therapy preparations
      for etiotropic RS-infection therapy. Procedures have been developed to prepare
      immunoglobulins and Chigain preparations having a target-oriented action. They
      were clinically tested. There was a positive dynamics in the clinical
      manifestations of the disease and a positive influence on immunological
      parameters in children.

PMID- 7580415
TI  - [Study of the nature and mechanism of action of virus neutralizing inhibitors of
      the blood].
AB  - Low-density lipoproteins (LDL, d 1.0.40-1.053 g/ml) and high-density lipoproteins
      (subfraction 3 of HDL, d 1.210 g/ml) were isolated by preparative
      ultracentrifugation at the NaBr density gradient. The findings have led to the
      conclusion that LDL or beta-LP are not thermolabile, but they represent a
      thermoresistant serum virus-inhibiting factor. At the same time HDL3 has
      pronounced thermolabile properties. The mechanisms of action of the above factors
      are explained in the paper.

PMID- 7580416
TI  - [Characteristics of monoclonal antibodies to RS virus in immunoenzyme and
      immunofluorescence techniques].
AB  - According to the competitive ELISA test data, new preparations of monoclonal
      antibodies (MAb) to respiratory syncytial virus (RSV) differed in their blocking
      activity and they were directed to 3 different virus epitopes. MAb 9C5 and MAb
      131-2A (CDC, Atlanta) competed against each other strongly and they were directed
      to epitope F1a of RSV F-protein. MAbs 8C5 and 10D8 showed a two-way blocking and
      were presumably topologically linked. MAb 8B10 did not compete against other
      MAbs. The fact that MAbs 8B10, 9C5, and 10D8 may be used in indirect ELISA test
      to detect RSV antigens was shown. The specific activity of MAbs 9C5 was observed,
      by applying low antibody concentrations to ng/mg. The highest specific activity
      using the homologous pair MAbs-con 9C5 and 8C5 was observed in direct ELISA
      employing MAbs for capture and peroxidase conjugate of MAbs for detection. MAbs
      8B10 were successfully used for direct (FITC-conjugate of MAbs) and indirect
      immunofluorescence detection of RSV antigens in the infected cell cultures and
      clinical materials from patients.

PMID- 7580417
TI  - [Clinical and laboratory characteristics of rotavirus infection in adults].
AB  - The paper provides clinical and laboratory characteristics of 21 patients aged 20
      80 years who had rotavirus infection, including 52% of 51-80-year-old inpatients.
      Recovery was observed in 15 cases, 6 patients died. The paper also characterizes
      the clinical course of rotavirus infection in the hospital setting and presents
      autopsy findings of the 6 decreased patients. The manifestations specific for
      rotavirus infection were identified to be involvement of serous and mucosal
      membranes predominantly of the small intestine, frequent development of serous
      peritonitis, as well as generalization of an infectious process afflicting the
      gallbladder, liver, heart, lung, and kidney.

PMID- 7580418
TI  - [Etiology of the infectious process in pulmonary and mixed forms of
      mucoviscidosis in children].
AB  - The specific features of an infectious process were studied in 150 children
      treated for mucoviscidosis at the State Pulmonology Research Center, Ministry of
      Health and Medical Industry of the Russian Federation. Hemophilic bacilli,
      Staphylococcus aureus, and Pseudomonas aeruginosa were fond to play the leading
      role in the etiology of the infectious process in the bronchopulmonary system.
      Pneumococcal infection was first ascertained to be important in the course of the
      disease. Developmental stages of a pyoinfectious process from the onset of its
      contamination, acute infection to chronic one were followed up. The most severe,
      prognostically unfavourable course of the disease was demonstrated to be
      associated with Pseudomonas aeruginosa infection.

PMID- 7580420
TI  - The way of the future: interdisciplinary research.

PMID- 7580421
TI  - United States nursing doctoral programs and nursing doctoral programs throughout
      the world.

PMID- 7580419
TI  - [Features of interepidemic influenza A and B viruses].
AB  - The comparison of interepidemic influenza viruses with the pathogens of resultant
      influenza epidemics has revealed that they belong to the same type (subtype) of
      influenza virus. A definite correlation has been found between the antigenic
      specificity of haemagglutinin of epidemic and interepidemic strains. The
      antigenic structure of the interepidemic viruses and the pathogens of further
      epidemics of influenza B viruses have been found to be completely identical. The
      interepidemic A(H1N1) isolates have been shown to be antigenic analogues of the
      causative agents of influenza A(H1N1) during the previous epidemics. Despite the
      time and place of their isolation, as well as the etiology of the previous and
      subsequent epidemics, the interepidemic influenza A(H3N2) viruses have been
      ascertained to be similar to the reference A/Bangkok/1/79.

PMID- 7580422
TI  - Advancing science.

PMID- 7580423
TI  - Nursing research shapes global health.

PMID- 7580424
TI  - Portrait of a Virginia Henderson fellow: Beverly M. Henry.

PMID- 7580425
TI  - Society funding fosters nursing knowledge.

PMID- 7580426
TI  - Newborn research depends on partnerships. Interview by Julie Goldsmith.

PMID- 7580427
TI  - Priorities and rationing: pragmatism or principles?

PMID- 7580428
TI  - Emergency contraception.

PMID- 7580429
TI  - Angiotensin converting enzyme genotypes and disease.

PMID- 7580430
TI  - Postoperative shivering: the influence of body temperature.

PMID- 7580432
TI  - Assessing the quality of care.

PMID- 7580431
TI  - Managing cleft lip and palate.

PMID- 7580434
TI  - France adopts new code of medical ethics.

PMID- 7580433
TI  - Global changes in climate will affect health.

PMID- 7580435
TI  - Conference on AIDS criticises inaction.

PMID- 7580436
TI  - Ireland announces compensation for hepatitis c.

PMID- 7580437
TI  - Birth weight and blood pressure: cross sectional and longitudinal relations in
      childhood.
AB  - OBJECTIVE: To examine cross sectional and longitudinal relations between birth
      weight and blood pressure in childhood. DESIGN: Cross sectional study of primary
      school children aged 9-11 years, with analysis in relation to previous
      measurements at 5-7 years in a subgroup. SETTING: 20 primary schools in Guildford
      and Carlisle. SUBJECTS: 1511 children measured at 9-11 years (response rate 79%),
      including 549 who had been measured at 5-7 years. MAIN OUTCOME MEASURES: Blood
      pressure at 9-11 years, change in blood pressure between 5-7 and 9-11 years,
      birth weight (based on maternal recall), and placental weight (based on birth
      records). RESULTS: At 9-11 years birth weight was inversely related both to
      systolic blood pressure (regression coefficient -2.80 mm Hg/kg; 95% confidence
      interval -3.84 to -1.76) and to diastolic blood pressure (regression coefficient 
      1.42 mm Hg/kg; -2.14 to -0.70) once current height and body mass index were taken
      into account. Placental weight was inversely related to blood pressure after
      adjustment for current height and body mass index but placental ratio (placental
      weight to birth weight) was unrelated to blood pressure. Between 5-7 and 9-11
      years systolic blood pressure rose more rapidly in children of lower birth weight
      (regression coefficient -1.71 mm Hg/kg; -3.35 to -0.07). This effect seemed to be
      stronger in girls. CONCLUSIONS: Birth weight rather than placental ratio is the
      early life factor most importantly related to blood pressure in childhood. The
      results support the possibility of "amplification" of the relation between birth
      weight and blood pressure, particularly in girls.

PMID- 7580439
TI  - Total cholesterol concentration and mortality at a relatively young age: do men
      and women differ?
AB  - OBJECTIVE: To investigate the relation between total cholesterol concentration
      and mortality from coronary heart disease, cardiovascular diseases, non
      cardiovascular causes, and all causes. DESIGN: Population based cohort study.
      SUBJECTS: 23,000 men and 26,000 women aged 30-54 years examined between 1974 and
      1980. MAIN OUTCOME MEASURES: Mortality for the above mentioned end points for
      fifths of cholesterol distribution, and relative risks estimated by using Cox's
      proportional hazard (survival) analysis. Adjustment was made for age, smoking,
      systolic blood pressure, and body mass index. RESULTS: Mortality from coronary
      heart disease in men was five times higher than that in women. A strong positive
      association between total cholesterol concentration and mortality from coronary
      heart disease and cardiovascular diseases was observed in both men and women. The
      relative risk for the highest compared with the lowest fifth of the cholesterol
      distribution was for mortality from coronary heart disease (3.0 (95% confidence
      interval 1.8 to 5.1) in men and 3.8 (1.1 to 13.1) in women) and for mortality
      from cardiovascular disease (2.8 (1.8 to 4.2) in men and 2.9 (1.4 to 6.0) in
      women). No increase of non-cardiovascular mortality at low cholesterol
      concentration was observed. All cause mortality was significantly higher in the
      highest compared with the lowest fifth of the cholesterol distribution: relative
      risk 1.6 (1.3 to 2.0) in men and 1.5 (1.1 to 1.9) in women. CONCLUSION: Total
      cholesterol concentration is a strong predictor of mortality from coronary heart
      disease, cardiovascular diseases, and all causes in women as well as in men. Low
      cholesterol concentrations are not associated with increased mortality from non
      cardiovascular causes.

PMID- 7580438
TI  - Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample.
AB  - OBJECTIVE: To establish the prevalence of Fc epsilon RI-beta polymorphisms Leu181
      and Leu181/Leu183 on chromosome 11q13 in the general population and to examine
      whether when maternally inherited they confer a risk of atopy. DESIGN: A
      population based survey for measures of atopy (skin prick test reactions,
      specific IgE titres, total serum IgE concentration), bronchial
      hyperresponsiveness, and carriage of Fc epsilon RI-beta Leu181 and Leu181/Leu183.
      SETTING: The rural coastal town of Busselton, Western Australia. SUBJECTS: 1004
      members of 230 two generation families identified through adults aged under 55.
      RESULTS: Fc epsilon RI-beta Leu181/Leu183 was identified in 45 subjects (4.5%).
      All 13 children who had inherited the variant maternally were atopic. Six had
      asthma and nine rhinitis. The odds ratio of a positive skin prick test reaction
      to house dust mite or grass pollen in these children compared with the other 523
      children was 7.37 (95% confidence interval 1.62 to 33.60). The 95% confidence
      interval for the odds ratio of a positive specific IgE response (radio
      allergosorbent test) was 3.00 to infinity, and the odds ratio for bronchial
      hyperresponsiveness was 3.70 (1.21 to 11.60). By contrast, the eight children who
      had derived the variant paternally had negative skin prick and
      radioallergosorbent test results and did not have increased bronchial
      responsiveness. CONCLUSION: Fc epsilon RI"' beta Leu181/Leu183 when inherited
      maternally identifies a genetic risk factor for atopy and bronchial
      hyperresponsiveness.

PMID- 7580440
TI  - Waiting list dynamics and the impact of earmarked funding.
AB  - OBJECTIVE: To determine how changes in the number of admissions from waiting
      lists and changes in the number of additions to the lists are related to list
      size and waiting times, in the context of local waiting list initiatives. DESIGN:
      Review of national and Korner statistics. SETTING: England (1987-94) and
      districts of the former Oxford region (1987-91). MAIN OUTCOME MEASURES:
      Correlation of quarterly changes in the number of admissions from waiting lists
      in England with changes in total list size, numbers of patients waiting one to
      two, or over two years, and number of additions to the lists; examination of
      changes in waiting list statistics for individual district specialties in one
      region in relation to funding for waiting list initiatives. RESULTS: Nationally,
      changes in the number of admissions to hospital from lists closely correlated
      with changes in the number of additions to lists (r = 0.84; P < 0.01). After
      adjusting for changes in the number of additions to lists, changes in the number
      of admissions correlated inversely with changes in list size (r = -0.62; P <
      0.001). Decreases in the number of patients waiting from one to two years were
      significantly associated with increases in the number of admissions (r = -0.52; P
      < 0.01); locally, only six of 44 waiting list initiatives were followed by an
      increase in admissions and a fall in list size, although a further 11 were
      followed by a fall in list size without a corresponding increase in admissions.
      CONCLUSIONS: An increase in admissions improved waiting times but did not reduce
      list size because additions to the list tended to increase at the same time. The
      appropriateness of waiting list initiatives as a method of funding elective
      surgery should be reviewed.

PMID- 7580441
TI  - Acquired immunodeficiency without HIV infection: epidemiology and clinical
      outcome in Italy. The Italian Study Group on non-HIV AIDS.

PMID- 7580442
TI  - Analysis from inner London of deprivation payments based on enumeration districts
      rather than wards.
AB  - OBJECTIVE: To estimate the effect of calculating the Jarman index using the
      smaller geographical unit of the census enumeration district on the changes in
      deprivation payments made to general practitioners. The Jarman index, or
      underprivileged area score, is used to calculate the allowance that general
      practices in the United Kingdom receive for each patient registered with them who
      lives in an area of relative social deprivation. Current values of the Jarman
      score are derived from the 1981 census and are based on electoral wards. The
      change in payments to some practices brought about by using data from the 1991
      census may cause severe financial hardship. DESIGN: Jarman indices for wards and
      enumeration districts from the 1981 and 1991 censuses were used to calculate the
      payments made to 169 practices in Lambeth, Southwark, and Lewisham; the changes
      in payments under ward and enumeration district based schemes were then compared.
      MAIN OUTCOME MEASURES: Standard deviations of the changes in payments to
      practices. Extreme values of changes in payments. RESULTS: The standard deviation
      of the change in payment between the two censuses was 6365 pounds with the
      enumeration district Jarman index, whereas it was 9452 pounds under the ward
      based scheme. If the ward based scheme is used 10 practices would find their
      payments changed by over 20,000 pounds, whereas only two practices would have
      changed by more than this amount under the scheme based on enumeration districts.
      CONCLUSION: The Jarman index could be more sensitively and appropriately applied
      to calculate the deprivation payments that practices receive using the census
      enumeration district as its unit for calculation. This would result in fewer
      precipitate changes in payments when census data change every 10 years.

PMID- 7580443
TI  - Interventional neuroradiology.

PMID- 7580444
TI  - Detecting differences in quality of care: the sensitivity of measures of process
      and outcome in treating acute myocardial infarction.
AB  - The merits or otherwise of publishing hospital specific death rates are much
      debated. This article compares the relative sensitivity of measures of process
      and outcome to differences in quality of care for the hospital treatment of
      myocardial infarction. Aspects of hospital care that have a proved impact on
      mortality from myocardial infarction are identified, and the results from meta
      analysis and large randomised controlled trials are used to estimate the impact
      that optimal use of these interventions would have on mortality in a typical
      district general hospital. Sample size calculations are then performed to
      determine how many years of data would be needed to detect significant
      differences between hospitals. A comparison is then made with the amount of data
      that would be needed to detect significant differences if information about
      process of care was being collected. Process measures based on the results of
      randomised controlled trials were found to be able to detect relevant differences
      between hospitals that would not be identified by comparing hospital specific
      mortality, which is an insensitive indicator of the quality of care.

PMID- 7580445
TI  - A purchaser perspective of managing new drugs: interferon beta as a case study.
AB  - Many new drugs in the future will be very expensive and have major resource
      implications. Given current structures and legislation covering the prescribing
      of drugs, there are no clear means of controlling the use of these drugs to avoid
      diverting money away from other health care services and into drug treatment.
      This paper considers what mechanisms might be used by a purchaser to manage the
      introduction of an expensive new drug and uses interferon beta-1b for treating
      multiple sclerosis as an example. The most likely mechanism is the prescribing of
      the drug by a general practitioner on the advice of a neurologist. This would
      achieve a good benefit for the resources invested but would not control total
      expenditure. Devolving a limited budget for the drug to a specialist centre so
      that neurologists may prescribe it directly would be preferable, as this would
      link clinical, prescribing, and budgetary responsibility. These issues need to be
      addressed urgently by purchasers if major disruptions of services are to be
      avoided.

PMID- 7580446
TI  - ABC of medical computing. Computers in general practice--I.

PMID- 7580447
TI  - Pregnant teenagers and contraception. Women know little about emergency
      contraception, and men know less.

PMID- 7580448
TI  - Psychiatric tourism is overloading London beds.

PMID- 7580449
TI  - Pregnant teenagers and contraception. Contraceptive failure may be a major factor
      in teenage pregnancy.

PMID- 7580450
TI  - Pregnant teenagers and contraception. The needs of older women are just as great.

PMID- 7580451
TI  - Serum cholesterol concentrations in parasuicide. Depression may cause low
      cholesterol.

PMID- 7580452
TI  - Serum cholesterol concentrations in parasuicide. Scottish study does not
      replicate findings.

PMID- 7580453
TI  - Serum cholesterol concentrations in parasuicide. No association between low
      cholesterol and violent death.

PMID- 7580454
TI  - Broader definitions of clinical effectiveness are needed.

PMID- 7580455
TI  - Nurses could halve GP workload.

PMID- 7580456
TI  - Risk factors for acanthamoeba keratitis. Population study is required to confirm
      results.

PMID- 7580457
TI  - Risk factors for acanthamoeba keratitis. Single use disposable contact lenses
      should cut risk.

PMID- 7580458
TI  - Commissioning complementary medicine. Evaluations of efficacy of treatments
      should be consistent.

PMID- 7580459
TI  - Commissioning complementary medicine. Homoeopathic hospitals have unique skill.

PMID- 7580460
TI  - Structural adjustment and health. Financial institutions must let go.

PMID- 7580461
TI  - Structural adjustment and health. Mission hospitals are a useful model.

PMID- 7580462
TI  - Every extracontractual referral is a jewel.

PMID- 7580463
TI  - Measles data are reliable.

PMID- 7580464
TI  - Treatment of children with asthma. Entrust parents with "crisis pack" of
      steroids.

PMID- 7580465
TI  - Managing the complications of childhood arthritis.

PMID- 7580467
TI  - Rationing: the case for "muddling through elegantly".

PMID- 7580466
TI  - Homoeopaths and chiropractors are sceptical about immunisation.

PMID- 7580468
TI  - Setting priorities for surgical waiting lists.

PMID- 7580469
TI  - Reflex sympathetic dystrophy. May be accompanied by involuntary movements.

PMID- 7580470
TI  - New equities of information in an electronic age.

PMID- 7580471
TI  - Reflex sympathetic dystrophy. Has been renamed complex regional pain syndrome.

PMID- 7580472
TI  - Asymptomatic retinal haemorrhage is common at altitude.

PMID- 7580473
TI  - Being on first name terms may signify greater respect.

PMID- 7580474
TI  - Dornase alfa for cystic fibrosis.

PMID- 7580475
TI  - Hospital management commended for first trimester spontaneous abortion.

PMID- 7580476
TI  - Mildly raised intraocular pressure is a risk factor, not glaucoma itself.

PMID- 7580477
TI  - Confusion over use of placebos in clinical trials.

PMID- 7580478
TI  - Pregnancy in women with cystic fibrosis.

PMID- 7580479
TI  - Community care and general practice.

PMID- 7580480
TI  - The new out of hours agreement for general practitioners.

PMID- 7580481
TI  - Primary health care and adolescence.

PMID- 7580482
TI  - And now, evidence based editing.

PMID- 7580483
TI  - Study shows two drugs are best for HIV infection.

PMID- 7580484
TI  - NHS trust faces bill for compensation in home takeover.

PMID- 7580486
TI  - Needle exchanges reduce HIV infection in US.

PMID- 7580485
TI  - British children face changing health risks.

PMID- 7580487
TI  - Playing politics with the poor: the cities.

PMID- 7580489
TI  - Morbidity and severity of illness during interhospital transfer: impact of a
      specialised paediatric retrieval team.
AB  - OBJECTIVE: To evaluate the morbidity and severity of illness during interhospital
      transfer of critically ill children by a specialised paediatric retrieval team.
      DESIGN: Prospective, descriptive study. SETTING: Hospitals without paediatric
      intensive care facilities in and around the London area, and a paediatric
      intensive care unit at a tertiary centre. SUBJECTS: 51 critically ill children
      transferred to the paediatric intensive care unit. MAIN OUTCOME MEASURES: Adverse
      events related to equipment and physiological deterioration during transfer.
      Paediatric risk of mortality score before and after retrieval. Therapeutic
      intervention score before and after arrival of retrieval team. RESULTS: Two (4%)
      patients had preventable physiological deterioration during transport. There were
      no adverse events related to equipment. Severity of illness decreased during
      stabilisation and transport by the retrieval team, suggested by the difference
      between risk of mortality scores before and after retrieval (P < 0.001). The
      median (range) difference between the two scores was 3.0 (-6 to 17).
      Interventions during stabilisation by the retrieval team increased, demonstrated
      by the difference between intervention scores before and after retrieval, median
      (range) difference between the two scores being 6 (-8 to 38) (P < 0.001).
      CONCLUSIONS: Our study indicates that a specialised paediatric retrieval team can
      rapidly deliver intensive care to critically ill children awaiting transfer. Such
      children can be transferred to a paediatric intensive care unit with minimal
      morbidity and mortality related to transport. There was no deterioration in the
      clinical condition of most patients during transfer.

PMID- 7580488
TI  - Decreasing HIV-1 seroprevalence in young adults in a rural Ugandan cohort.
AB  - OBJECTIVE: To assess the trend in HIV-1 seroprevalence in an adult population in
      Uganda. DESIGN: An observational cohort study with four year follow up. SETTING:
      A cluster of 15 villages in rural Uganda. SUBJECTS: All residents of the 15
      villages--about 10,000 people. MAIN OUTCOME MEASURE: Prevalence of HIV-1
      infection as assessed by enzyme immunoassay. RESULTS: During the five year period
      the overall standardised seroprevalence of HIV-1 showed little change; 8.2% in
      1990, 7.6% in 1994. Among males aged 13-24 years the prevalence decreased from
      3.4% to 1.0% (P for trend < 0.001); among females of the same age the
      corresponding values were 9.9% and 7.3%. The decrease was greatest in males aged
      20-24 years and females aged 13-19 years. CONCLUSION: This is the first report of
      a decline in HIV-1 prevalence among young adults in a general population in sub
      Saharan Africa with high overall HIV-1 prevalence. It is too early to conclude
      that the epidemic in this population is in decline, but the results of this study
      should be reason for some cautious optimism and encourage the vigorous pursuit of
      AIDS control measures.

PMID- 7580490
TI  - Socioeconomic variation in admission for diseases of female genital system and
      breast in a national cohort aged 15-43.
AB  - OBJECTIVE: To investigate socioeconomic variation among young women in the risk
      of hospital admission for diseases (including neoplasms) of the female genital
      system and breast and for the common surgical procedures of dilatation and
      curettage and hysterectomy. DESIGN: Large nationally representative cohort study
      with individual records of confirmed admissions to NHS and private hospitals
      since birth and data on occupational and educational experience. SETTING:
      England, Scotland, and Wales. PATIENTS: General population sample of 1628 women,
      1549 of whom had a complete admissions record for the ages of 15-43 years. MAIN
      OUTCOME MEASURES: The percentage of women admitted for neoplasms or other
      diseases of the female genital system and breast or who had dilatation and
      curettage or hysterectomy between the ages of 15 and 43 years. RESULTS: By the
      age of 43, 35% of women had been admitted, 17% had undergone dilatation and
      curettage at least once, and 10% had had a hysterectomy. There were significant
      inverse educational gradients, the risk of admission increasing more than twofold
      between the most and least educated women. The differential risk was most
      striking for disorders of menstruation, in which only 1% of those with the
      highest educational qualifications and 19% of those with minimal qualifications
      had been admitted to hospital. There was a significant educational gradient in
      the hysterectomy rate (from 1% to 15%) and a twofold difference in the risk of
      dilatation and curettage. There were also significant gradients in risk of
      admission and of hysterectomy according to partner's social class. CONCLUSIONS:
      Socioeconomic variations in the risk of dilatation and curettage and of
      hysterectomy were large. Lessening the socioeconomic gradient in risks of
      admissions and surgery for diseases of the female genital system and breast,
      particularly for menstrual disorders, could have important resource implications.

PMID- 7580491
TI  - Denial of effective treatment and poor quality of clinical information in placebo
      controlled trials of ondansetron for postoperative nausea and vomiting: a review
      of published trials.
AB  - OBJECTIVE: To determine how many patients were deprived of treatment by being
      given placebo as comparator in trials of ondansetron for postoperative nausea and
      vomiting. DESIGN: Review of published trials of ondansetron during 1991 to July
      1994. SETTING: Medline search in a university department of anaesthesia.
      SUBJECTS: 8806 patients who had been included in 18 indexed placebo controlled
      trials of ondansetron as prophylaxis against or treatment of postoperative nausea
      and vomiting. RESULTS: Five studies (1236 patients) had been published by July
      1992. All were placebo controlled trials. By July 1994, 8806 patients had been
      included in 18 indexed placebo controlled studies of prophylaxis or treatment.
      Only 462 patients had been in studies that compared ondansetron with other drugs,
      and there were no indexed comparative trials of treatment of nausea and vomiting.
      Roughly 2180 patients had been given placebo as prophylaxis and 440 had been
      given placebo when already experiencing postoperative nausea or vomiting.
      CONCLUSIONS: Around 2620 patients in the reviewed studies were denied existing
      drugs, which, though not completely effective or without side effects, do bring
      some relief from postoperative nausea and vomiting. Drug regulatory bodies should
      collaborate with drug companies to ensure better comparison of new with
      established drugs. This would avoid placebos being given to more than the fewest
      patients necessary to confirm effect and would allow doctors to be informed more
      quickly about relative efficacies.

PMID- 7580492
TI  - Incidence of transfusion associated B and non-A, non-B hepatitis in Italy.

PMID- 7580493
TI  - Prevalence of alcohol histories in medical and nursing notes of patients admitted
      with self poisoning.

PMID- 7580494
TI  - Has general practitioner computing made a difference to patient care? A
      systematic review of published reports.
AB  - OBJECTIVE: To review findings from studies of the influence of desktop computers
      on primary care consultations. DESIGN: Systematic review of world reports from
      1984 to 1994. SETTING: The computerised catalogues of Medline, BIDS, and GPlit
      were searched, as well as conference proceedings, books, bibliographies, and
      references in books and journal articles. SUBJECTS: 30 papers met the inclusion
      criteria and were included for detailed review. INTERVENTIONS: A validated scheme
      for assessing methodological adequacy was used to score each paper. MAIN OUTCOME
      MEASURES: Papers were rated on sample formation, baseline differences, unit of
      allocation, outcome measures, and follow up. Differences in outcomes were also
      recorded. RESULTS: Four of the six papers dealing with the consultation process
      showed that consultations took longer. Doctor initiated and "medical" content of
      consultations increased at the expense of a reduction in patient initiated and
      "social" content. Each of the 21 studies which looked at clinician performance
      showed an improvement when a computer was used (from 8% to 50%, with better
      results for single preventive measures). Only one of the three studies looking at
      patient outcomes showed an improvement (diastolic blood pressure control 5 mm Hg
      better after one year, with fewer doctor-patient consultations). CONCLUSIONS:
      Using a computer in the consultation may help improve clinician performance but
      may increase the length of the consultation. More studies are needed to assess
      the effects on patient outcomes of using a computer in consultations.

PMID- 7580495
TI  - Management of hip osteoarthritis.

PMID- 7580496
TI  - Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor
      medical practice.
AB  - OBJECTIVE: To investigate two hospital outbreaks of Lassa fever in southern
      central Nigeria. SETTING: Hospitals and clinics in urban and rural areas of Imo
      State, Nigeria. DESIGN: Medical records were reviewed in hospitals and clinics in
      both areas. Patients with presumed and laboratory confirmed Lassa fever were
      identified and contracts traced. Hospital staff, patients, and local residents
      were questioned, records were carefully reviewed, and serum samples were taken.
      Serum samples were assayed for antibody specific to Lassa virus, and isolates of
      Lassa virus were obtained. RESULTS: Among 34 patients with Lassa fever, including
      20 patients, six nurses, two surgeons, one physician, and the son of a patient,
      there were 22 deaths (65% fatality rate). Eleven cases were laboratory confirmed,
      five by isolation of virus. Most patients had been exposed in hospitals (attack
      rate in patients in one hospital 55%). Both outbreak hospitals were inadequately
      equipped and staffed, with poor medical practice. Compelling, indirect evidence
      revealed that parenteral drug rounds with sharing of syringes, conducted by
      minimally educated and supervised staff, fuelled the epidemic among patients.
      Staff were subsequently infected during emergency surgery and while caring for
      nosocomially infected patients. CONCLUSION: This outbreak illustrates the high
      price exacted by the practice of modern medicine, particularly use of parenteral
      injections and surgery, without due attention to good medical practice. High
      priority must be given to education of medical staff in developing countries and
      to guidelines for safe operation of clinics and hospitals. Failure to do so will
      have far reaching, costly, and ultimately devastating consequences.

PMID- 7580497
TI  - Tropical medicine for the 21st century.
AB  - The specialty of tropical medicine originated from the needs of the colonial era
      and is removed from many of the health care requirements of tropical countries
      today. Tropical medicine concentrates on parasitic diseases of warm climates,
      although other infections and diseases related to poverty rather than climate
      dominate medicine in developing countries challenged by population pressure,
      civil strife, and migration. In the new century, tropical medicine would best be
      absorbed into the specialty of infectious diseases, which should incorporate
      parasitic diseases, travel medicine, and sexually transmitted diseases. Pressing
      questions for health care and research in developing countries concern the
      provision of appropriate services for problems such as HIV/AIDS, tuberculosis,
      sexually transmitted diseases, and injuries. The question of how to provide
      appropriate clinical care in resource poor settings for the major causes of
      morbidity and premature mortality has been neglected by donors, academic
      institutions, and traditional tropical medicine.

PMID- 7580498
TI  - Harnessing the strengths of the leprosy programme to control tuberculosis.
AB  - Tuberculosis remains a leading cause of death in Ethiopia but there is no
      effective national tuberculosis control programme. By contrast, the leprosy
      control programme has been very successful, with a 10-fold reduction in the
      number of leprosy cases requiring antibacterial treatment, though patients with
      nerve damage require continuing care. The paradox of rising numbers of
      tuberculosis cases and declining numbers of leprosy cases may be solved by joint
      leprosy-tuberculosis clinics. The strengths of leprosy fieldworkers in control
      management, case holding, and compliance can be harnessed in developing an
      effective tuberculosis control programme. Implementing a joint programme in
      Ethiopia may be beneficial not only for tuberculosis patients but also for
      leprosy patients, who are thus brought closer to general medical services.

PMID- 7580499
TI  - ABC of medical computing. Computers in general practice--II.

PMID- 7580500
TI  - Treating CS gas injuries to the eye. Exposure at close range is particularly
      dangerous.

PMID- 7580501
TI  - Treating CS gas injuries to the eye. Illegal "Mace" contains more toxic CN
      particles.

PMID- 7580502
TI  - Treating CS gas injuries to the eye. Poisons centre will monitor cases.

PMID- 7580503
TI  - Pitfalls in the diagnosis of subarachnoid haemorrhage.

PMID- 7580504
TI  - Medicine and nursing. Medicine and nursing need both scientific and naturalistic
      inquiry.

PMID- 7580505
TI  - Medicine and nursing. Nurses should have experience of medical training.

PMID- 7580506
TI  - Medicine and nursing. Senior nurses are out of touch.

PMID- 7580507
TI  - Medicine and nursing. Problems of hierarchy are not confined to nursing.

PMID- 7580508
TI  - Macintosh PC is better than Windows.

PMID- 7580509
TI  - Medicine and nursing. Nurses' role is narrowing in Germany.

PMID- 7580510
TI  - Medicine and nursing. Nursing euologies ignored ethos of control and punishment.

PMID- 7580511
TI  - Software package makes counting episodes easier.

PMID- 7580512
TI  - Incidence of gastrointestinal bleeding in Italy is similar to that in Britain.

PMID- 7580513
TI  - Vitamin D receptor genotype and bone mineral density. Evidence conflicts on link.

PMID- 7580514
TI  - Psychosis is also common in users of "normal" cannabis.

PMID- 7580515
TI  - Allocating census data to general practice populations. Survey data have their
      problems too.

PMID- 7580516
TI  - Allocating census data to general practice populations. Reducing number of
      postcodes that cannot be ascribed would increase validity of method.

PMID- 7580517
TI  - Fall in birth weight of third generation Asian infants.

PMID- 7580518
TI  - Treating temporarily incompetent patients. Competence cannot be determined by
      reasonableness of patient's decision.

PMID- 7580519
TI  - Diabetes and breast feeding. Carbohydrate requirements are increased.

PMID- 7580520
TI  - Diabetes and breast feeding. Support is available for diabetic mothers.

PMID- 7580521
TI  - Treating temporarily incompetent patients. General practitioners can help with
      patients who take their own discharge.

PMID- 7580522
TI  - Treating temporarily incompetent patients. No reasonable doubt that patient was
      incompetent.

PMID- 7580523
TI  - Ambulance staff exercise discretion over resuscitation decision.

PMID- 7580524
TI  - New measures can help to measure economic "externalities".

PMID- 7580525
TI  - Pig sticking injuries are no joke.

PMID- 7580526
TI  - BMJ should declare its own conflict of interest.

PMID- 7580527
TI  - Biomedical journals not dead yet. Electronic publications are hard to access.

PMID- 7580528
TI  - Biomedical journals not dead yet. Whimsical titles are deeply unhelpful.

PMID- 7580529
TI  - Information on sugar free medicines is readily available.

PMID- 7580530
TI  - Unreliability of reports of hypoglycaemia by diabetic patients.

PMID- 7580531
TI  - Depression, antidepressants, and accidents.

PMID- 7580532
TI  - Palliative care in general practice.

PMID- 7580533
TI  - Chemotherapy for non-small cell lung cancer.

PMID- 7580534
TI  - Defining ischaemia.

PMID- 7580535
TI  - Primary health care led NHS: learning from developing countries.

PMID- 7580536
TI  - Human genome moves closer to reality.

PMID- 7580537
TI  - Flying doctor service faces reforms.

PMID- 7580539
TI  - Relief workers need professionalism.

PMID- 7580538
TI  - Dutch court rules on nurses' role in euthanasia.

PMID- 7580540
TI  - France debates ethics of sperm injection techniques.

PMID- 7580541
TI  - South Africa prepares for drug battle.

PMID- 7580542
TI  - Russia warned of collapse of health system.

PMID- 7580544
TI  - French minister promises action to clean up asbestos.

PMID- 7580543
TI  - Vision of a golden age: cancer charity looks to the future.

PMID- 7580545
TI  - Healthcare analysis cuts no ice in Whitehall.

PMID- 7580546
TI  - Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on
      individual patients from 52 randomised clinical trials. Non-small Cell Lung
      Cancer Collaborative Group.
AB  - OBJECTIVE: To evaluate the effect of cytotoxic chemotherapy on survival in
      patients with non-small cell lung cancer. DESIGN: Meta-analysis using updated
      data on individual patients from all available randomised trials, both published
      and unpublished. SUBJECTS: 9387 patients (7151 deaths) from 52 randomised
      clinical trials. MAIN OUTCOME MEASURE: Survival. RESULTS: The results for modern
      regimens containing cisplatin favoured chemotherapy in all comparisons and
      reached conventional levels of significance when used with radical radiotherapy
      and with supportive care. Trials comparing surgery with surgery plus chemotherapy
      gave a hazard ratio of 0.87 (13% reduction in the risk of death, equivalent to an
      absolute benefit of 5% at five years). Trials comparing radical radiotherapy with
      radical radiotherapy plus chemotherapy gave a hazard ratio of 0.87 (13% reduction
      in the risk of death; absolute benefit of 4% at two years), and trials comparing
      supportive care with supportive care plus chemotherapy 0.73 (27% reduction in the
      risk of death; 10% improvement in survival at one year). The essential drugs
      needed to achieve these effects were not identified. No difference in the size of
      effect was seen in any subgroup of patients. In all but the radical radiotherapy
      setting, older trials using long term alkylating agents tended to show a
      detrimental effect of chemotherapy. This effect reached conventional significance
      in the adjuvant surgical comparison. CONCLUSION: At the outset of this meta
      analysis there was considerable pessimism about the role of chemotherapy in non
      small cell lung cancer. These results offer hope of progress and suggest that
      chemotherapy may have a role in treating this disease.

PMID- 7580547
TI  - Survival in families with hereditary protein C deficiency, 1820 to 1993.
AB  - OBJECTIVES: To establish the survival of individuals heterozygous for hereditary
      protein C deficiency, who have an increased risk of venous thrombotic events, and
      to compare it with the survival of the general population. DESIGN: Retrospective
      study in pedigrees of 23 families with hereditary protein C deficiency for period
      1820 and 1993. SETTING: 23 completed family trees of 24 probands from various
      parts of the Netherlands with symptoms of protein C deficiency. SUBJECTS: All 736
      members of the 23 families with a 50% or 100% probability of being (or having
      been) heterozygous for the genetic defect on the basis of DNA analysis or their
      place in the pedigrees, following mendelian rules. MAIN OUTCOME MEASURES:
      Observed mortality compared with the mortality of the general Dutch population;
      the standardised mortality ratio was calculated by dividing the observed
      mortality by the expected mortality. RESULTS: No excess mortality was found in
      the 206 proved heterozygous individuals and "obligatory transmitters" (those who
      have definitely passed on the deficiency) (standardised mortality ratio 0.95 (95%
      confidence interval 0.5 to 1.2)) or in the 530 family members with a 50% genetic
      probability of heterozygosity (1.10 (0.9 to 1.3)). CONCLUSION: Heterozygous
      individuals with hereditary protein C deficiency type I have normal survival
      compared with the general population. Prophylactic anticoagulant treatment may
      prevent thrombotic events in heterozygous individuals but may not be expected to
      improve their survival.

PMID- 7580549
TI  - Increasing prescription of drugs for secondary prevention after myocardial
      infarction.

PMID- 7580548
TI  - Concordance rates of insulin dependent diabetes mellitus: a population based
      study of young Danish twins.
AB  - OBJECTIVE: To study the genetic contribution to the aetiology of insulin
      dependent diabetes mellitus. DESIGN: Historical cohort study of twins, with
      information on diabetes being gathered by questionnaire, verification of the
      diagnosis by the subject's diabetologist or general practitioner, and clinical
      examination in available twins. SETTING: Danish twin register and diabetic
      clinics and general practices throughout Denmark. SUBJECTS: 20,888 twin pairs
      born during 1953-82, included in a population based nationwide register. MAIN
      OUTCOME MEASURES: Crude and cumulative concordance rates and heritability in
      monozygotic and dizygotic twins. RESULTS: The crude probandwise concordance rate
      was 0.53 (95% confidence interval 0.33 to 0.73) for monozygotic twin pairs and
      0.11 (0.05 to 0.21) for dizygotic twin pairs. When adjusted for age at onset of
      diabetes and age at last observation among unaffected twin partners the
      cumulative proband-wise risk from birth to age 35 was estimated as 0.70 (0.45 to
      0.95) for monozygotic twins and 0.13 (0.05 to 0.20) for dizygotic twins. The
      correlations of liability for monozygotic and dizygotic twin pairs were estimated
      as 0.96 (SE 0.09) and 0.58 (0.07), with a heritability estimate of 0.72 (0.21).
      CONCLUSIONS: The risk of insulin dependent diabetes in monozygotic twins is
      higher than previously thought and for dizygotic twins is higher than in ordinary
      first degree relatives. Based on the findings of this study the genetic component
      to the disease seems more important than hitherto believed.

PMID- 7580550
TI  - Audit of reports of randomised clinical trials published in one journal over 45
      years.

PMID- 7580552
TI  - Measles and rubella immunisation: information and consent in children.

PMID- 7580551
TI  - Randomised double blind comparison of terbinafine and itraconazole for treatment
      of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group.
AB  - OBJECTIVE: To compare the efficacy and tolerability of terbinafine and
      itraconazole in the treatment of toenail tinea unguium. DESIGN: Multicentre,
      double blind, parallel group study. SETTING: 17 university hospitals, one army
      hospital, and five dermatology practices. PATIENTS: 195 patients with clinically
      suspected toenail tinea and growth of dermatophytes in baseline culture; data on
      86 patients in the terbinafine group and 84 patients in the itraconazole group
      were fully evaluated for efficacy. INTERVENTIONS: Daily dose of 250 mg
      terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40
      weeks. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy
      and culture) and clinical improvement (length and area of unaffected nail) at
      week 52 or at discontinuation of treatment. RESULTS: At the end of the study
      mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of
      84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of
      86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P
      < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and
      7.85 mm in the itraconazole group (2P < 0.05). CONCLUSION: Terbinafine is more
      effective than itraconazole in the treatment of toenail tinea infection.

PMID- 7580553
TI  - Fever can cause pyuria in children.

PMID- 7580554
TI  - Social policy as a cause of childhood accidents: the children of lone mothers.
AB  - Almost one in five British mothers is a lone mother. Their children have injury
      rates that are twice those of children in two parent families. In this article
      the link between lone parenthood and childhood injury is examined. The increased
      injury rates for the children of lone mothers can be explained by the poverty,
      poor housing conditions, and social isolation of lone mothers in Britain. The
      problem of reconciling the demands of paid work with the demands of the unpaid
      work of childrearing is particularly difficult for lone mothers, who find
      themselves in a benefit dependent poverty trap. Many such mothers would seek paid
      work if affordable day care were available. Day care would also provide a safe
      environment for their children, who are otherwise exposed to the environmental
      hazards of poor housing. Provision of day care is a social policy that would have
      important effects on the health and welfare of lone mothers and their children.
      These effects deserve to be properly evaluated.

PMID- 7580556
TI  - Improving oral examinations: selecting, training, and monitoring examiners for
      the MRCGP. Royal College of General Practitioners.
AB  - Unless examiners are carefully selected, trained, and monitored, examinations may
      become haphazard. This is perhaps most true of oral or viva voce ("viva")
      examinations, which can generate marks unrelated to competence. To help other
      bodies to short circuit some years of experiment in connection with the oral
      component of the Royal College of General Practitioners' membership examination
      (MRCGP), this paper describes the selection, training, guidance, and monitoring
      arrangements that have been developed.

PMID- 7580555
TI  - Voluntary, named testing for HIV in a community based antenatal clinic: a pilot
      study.
AB  - Despite the increasing advantages of identifying HIV infection in pregnant women,
      only some 12% of HIV positive women attending antenatal clinics in London have
      been identified by named testing. As virtually all antenatal care will be
      community based within the next two to three years, we assessed the problems of
      introducing named HIV testing during pregnancy into the primary care setting.
      Planning the service took a considerable time and required the production of
      educational material for both staff and pregnant women and some reorganisation of
      procedures. Over a one year period an uptake of 44% was noted. Several problems
      were encountered including an average of 21 minutes needed to give information on
      AIDS and HIV, an adverse effect on the midwife-mother relationship, and anxiety
      (affecting both women and midwives). Possible solutions to this difficult problem
      are discussed.

PMID- 7580557
TI  - Cuba: plenty of care, few condoms, no corruption.
AB  - The health system in Cuba guarantees accessibility to the entire population, is
      free of charge, and covers the spectrum from vaccinations to sophisticated
      interventions. The results are impressive: Cuba's health figures are on a par
      with developed countries that have 20 times the budget. The country is
      experiencing a difficult period because of the collapse and loss of support from
      the Soviet Union; over 30 years' trade embargo by the United States; and the
      gradual change from a centrally planned economy towards more of a free market
      system. Shortages are experienced in every sector, and maintaining health care
      services at the current level is too expensive. Doctors and nurses continue to
      work towards the goal of health for all Cubans, even though their salaries are
      minimal. Signs of negligence or corruption, often seen in other socialist
      countries where incentives for output are lacking, are unknown. Topics such as
      family planning and AIDS deserve immediate attention.

PMID- 7580558
TI  - ABC of medical computing. Computers in general practice--III.

PMID- 7580559
TI  - Doctors who smoke. Doctors should advise but do not have to lead by example.

PMID- 7580560
TI  - Doctors who smoke. Little progress has been made over 20 years.

PMID- 7580561
TI  - Doctors who smoke. Medical students should be educated about their exemplary
      role.

PMID- 7580562
TI  - Doctors who smoke. Why not exclude doctors with other unhealthy habits too?

PMID- 7580563
TI  - Doctors who smoke. Zealotry is counter productive.

PMID- 7580564
TI  - Assertions about patient information are not supported.

PMID- 7580565
TI  - Working in a developing country. Returned volunteers can advise.

PMID- 7580566
TI  - Working in a developing country. Which is good experience.

PMID- 7580567
TI  - South Africa's health. Apartheid cut both ways.

PMID- 7580568
TI  - South Africa's health. Ethnic differences in health are seen in other countries.

PMID- 7580569
TI  - South Africa's health. Psychiatric data are questionable.

PMID- 7580570
TI  - Health psychologists make an important contribution to care.

PMID- 7580571
TI  - South Africa's health. Traditional healers may cause dangerous delays.

PMID- 7580572
TI  - Treating temporarily incompetent patients. Depression calls into question
      patients' capacity to refuse treatment.

PMID- 7580573
TI  - No reliable evidence that folate is harmful in B-12 deficiency.

PMID- 7580574
TI  - Treating temporarily incompetent patients. Failure to treat outweigh risk of non
      voluntary treatment.

PMID- 7580575
TI  - Qualitative study on patients with stroke. Leaves questions unanswered.

PMID- 7580576
TI  - Advice on alcohol consumption has narrow perspective.

PMID- 7580577
TI  - Elective ventilation of potential organ donors.

PMID- 7580578
TI  - Other factors may have contributed to epidemic of renal failure.

PMID- 7580579
TI  - Developing a standard dataset for the NHS. Read codes' primary use is clinical.

PMID- 7580580
TI  - Developing a standard dataset for the NHS. Version 3 of read codes addresses many
      difficulties.

PMID- 7580581
TI  - Treatment for cancer pain.

PMID- 7580582
TI  - General practitioners' role in emergencies.

PMID- 7580583
TI  - Measurement of bone density in osteoporosis.

PMID- 7580584
TI  - Videotaping of general practice consultations.

PMID- 7580585
TI  - New deal shifts may increase house officers' stress.

PMID- 7580586
TI  - Concerns about "lookback" exercise for hepatitis C.

PMID- 7580587
TI  - Faulty blood bags.

PMID- 7580588
TI  - Commentary: life in the real world is more complicated.

PMID- 7580591
TI  - Beijing diary: ten days at the women's conference.

PMID- 7580589
TI  - Towards the safer use of medicines.
AB  - In Britain the tools are now available to provide better information on safety of
      medicines in both hospital and community settings, and this could be done at
      relatively modest cost. The needs of patients, doctors, and pharmacists are
      changing; although more research is needed, such information as is presently
      available must be both better and more widely publicised and understood.
      Universities, government, the pharmaceutical industry, and educated journalism
      all have an important part to play in this process.

PMID- 7580590
TI  - Department of Health's requirement for mandatory collection of data on ethnic
      group of inpatients.
AB  - On 1 April the Department of Health introduced the mandatory collection of data
      on the ethnic group of patients admitted to hospital. Its coding was based on a
      national minimum standard for classifying ethnic groups, ostensibly using the
      categories in the 1991 census. In the census, however, one in four people from
      ethnic groups other than white, including many of mixed parentage, provided non
      standard responses to the question on ethnic group. The Department of Health's
      standard does not include provision for respondents to write in a description of
      their ethnic group, and this has produced a flawed system out of step with
      current practice on collection of data on ethnic group. Different methods of
      analysis preclude comparison with census statistics, and the difficulties in
      aggregating more detailed local categories to the standard raise concerns about
      consistency of reporting and quality of the data.

PMID- 7580592
TI  - ABC of medical computing. Hospital based computer systems.

PMID- 7580593
TI  - Cycling and physical exercise. Cycling has "street cred" among young people.

PMID- 7580594
TI  - Cycling and physical exercise. Government's endorsement of cycling is welcome U
      turn.

PMID- 7580595
TI  - Patients with a self diagnosis of myalgic encephalomyelitis.

PMID- 7580596
TI  - Cycling and physical exercise. Cycling is one of most common forms of sport and
      recreation.

PMID- 7580597
TI  - Falls due to stroke. Drug treatment and mental status of study patients is
      unclear.

PMID- 7580598
TI  - Predicting acute maxillary sinusitis. Trial may have lacked power.

PMID- 7580599
TI  - Predicting acute maxillary sinusitis. Trial was wrong to ignore other sinuses.

PMID- 7580600
TI  - Acute pain services. Purchasers must be prepared to pay for a multidisciplinary
      team.

PMID- 7580601
TI  - Ensuring that guidelines are effective. Give them to the patient.

PMID- 7580602
TI  - Ensuring that guidelines are effective. Pilot of patient held guidelines is under
      way.

PMID- 7580604
TI  - Acute pain services. Low expectations of pain relief encourage persistence of
      poor standards.

PMID- 7580603
TI  - Acute pain services. Work is needed to show that good quality analgesia improves
      outcome of surgery.

PMID- 7580605
TI  - Anaesthetics training in the United States. America offers far less experience
      than Britain.

PMID- 7580606
TI  - Anaesthetics training in the United States. Three year residency produces
      equivalent of competent middle grade registrar.

PMID- 7580607
TI  - Applying for flexible training. Application process is too slow.

PMID- 7580608
TI  - Applying for flexible training. Process has since been simplified.

PMID- 7580609
TI  - Differences in mortality after fracture of hip.

PMID- 7580610
TI  - Genetic testing in the classroom.

PMID- 7580611
TI  - Maintaining clinical contact during research.

PMID- 7580612
TI  - South African Medical Association colluded with apartheid.

PMID- 7580613
TI  - Extracontractual referrals. Budgets need to be increased to realistic level.

PMID- 7580614
TI  - Colleges and trusts are blocking humanitarian service.

PMID- 7580615
TI  - Extracontractural referrals. Panel has reduced inappropriate requests.

PMID- 7580616
TI  - General practice at night. New agreement penalises doctors who do their own on
      call.

PMID- 7580617
TI  - General practice at night. And finally, in the good old days...

PMID- 7580618
TI  - General practice at night. GPs should be given breathing space to cope.

PMID- 7580619
TI  - General practice at night. New agreement is not the answer but an opportunity.

PMID- 7580620
TI  - General practice at night. New money should be divided equally amongst all GPs.

PMID- 7580621
TI  - General practice at night. Service must change to deal with patients' reasonable
      demands.

PMID- 7580622
TI  - The scientific basis of health services.

PMID- 7580623
TI  - Consensus on red cell transfusion.

PMID- 7580624
TI  - Friday the 13th and obsessive compulsive disorder.

PMID- 7580626
TI  - Only doing my duty?

PMID- 7580625
TI  - Domestic violence against women.

PMID- 7580628
TI  - Medicare plans outrage elderly people and doctors.

PMID- 7580627
TI  - Hospital jobs on the Internet.

PMID- 7580629
TI  - France gears up to fight health insurance debts.

PMID- 7580630
TI  - Dutch propose paying GPs more for difficult work.

PMID- 7580631
TI  - Multiple sclerosis drug prompts rationing fears.

PMID- 7580632
TI  - Labour sets out high tech vision for NHS.

PMID- 7580633
TI  - Research must be declared by trusts and universities.

PMID- 7580634
TI  - US apologises for radiation tests on unaware patients.

PMID- 7580635
TI  - Autologous blood transfusions need risk register.

PMID- 7580636
TI  - Australian doctors in confidentiality controversy.

PMID- 7580637
TI  - Intensive therapy and progression to clinical albuminuria in patients with
      insulin dependent diabetes mellitus and microalbuminuria. Microalbuminuria
      Collaborative Study Group, United Kingdom.
AB  - OBJECTIVE: To study the effect of intensive therapy of diabetes on the
      progression to clinical albuminuria in insulin dependent diabetic patients with
      microalbuminuria. DESIGN: Randomised controlled clinical trial of intensive
      versus conventional therapy of diabetes for a median of 5 years (range 2-8).
      SETTING: Nine hospital based specialist diabetes centres in England and Wales.
      SUBJECTS: 70 European insulin dependent diabetic patients aged 17-59 years with
      microalbuminuria (albumin excretion 30-199 micrograms/min), but without arterial
      hypertension, recruited from the nine hospital based specialist diabetes centres.
      INTERVENTIONS: Intensive diabetic therapy was allocated to 36 patients (27 men, 9
      women) and conventional diabetic therapy to 34 (24 men, 10 women). MAIN OUTCOME
      MEASURES: Development of clinical albuminuria, defined as albumin excretion
      greater than 200 micrograms/min on at least two consecutive occasions, and rate
      of change of albumin excretion. RESULTS: Mean glycated haemoglobin concentration,
      similar at baseline in the two groups (intensive therapy group 10.3% (SEM 1.9%),
      conventional therapy group 9.8% (1.6%)), fell significantly (by 14%) in the
      intensive therapy group only. A significant glycaemic separation between the two
      groups was maintained for up to three years. Progression to clinical albuminuria
      occurred in six patients in each group. Blood pressure, similar at baseline, fell
      significantly by 1 mm Hg (95% confidence interval -4.20 to 1.43) per year in the
      conventional therapy group, but the difference in the rate of blood pressure
      change between the groups was not significant. Independent of treatment
      assignment, a mean blood pressure above the group mean (93.6 mm Hg), but not the
      glycated haemoglobin concentration, predicted progression to clinical albuminuria
      (relative risk 4.2, 95% confidence interval 1.3 to 13.0). CONCLUSIONS: Intensive
      therapy with improved glycaemic control for three years had no impact on the
      progression of albuminuria in insulin dependent diabetic patients with
      microalbuminuria. The reduction in blood pressure in the conventional therapy
      group may have affected outcome--in that arterial blood pressure rather than
      glycated haemoglobin concentration seemed to be the main predictor of progression
      from microalbuminuria to clinical albuminuria.

PMID- 7580638
TI  - Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast
      cancer in a randomised trial. The Scottish Cancer Trials Breast Group.
AB  - OBJECTIVE: To determine any cardiac or vascular morbidity associated with long
      term treatment with tamoxifen given after mastectomy for primary breast cancer.
      DESIGN: Cohort study using linkage between database of a randomised trial and
      statistics of Scottish hospital inpatients to identify episodes of cardiac and
      vascular morbidity. SETTING: NHS hospitals in Scotland. SUBJECTS: 1312 women who
      had undergone mastectomy for breast cancer and who were randomised either to a
      treatment group to receive adjuvant tamoxifen or to a control group to be given
      tamoxifen only on first relapse of disease. Maximum duration of tamoxifen
      treatment was 14 years. Total woman years of follow up were 9943. MAIN OUTCOME
      MEASURES: Randomised and observational comparisons of risk (expressed as hazard
      ratios) of myocardial infarction, other cardiac event, cerebrovascular disease,
      or thromboembolic event according to treatment allocated and between nonusers,
      former users, and current users of tamoxifen. RESULTS: Use of tamoxifen was
      associated with lower rates of myocardial infarction. Hazard ratio for women in
      control group was 1.92 (95% confidence interval 0.99 to 3.73) compared with women
      allocated to adjuvant treatment. The association was stronger for current use:
      hazard ratio for non-users was 3.49 (1.52 to 8.03) compared with current users.
      Current users of tamoxifen, however, had higher rates of thromboembolic
      events:hazard ratio for non-users was 0.40 (0.18 to 0.90) compared with current
      users. CONCLUSIONS: Our results provide further evidence that tamoxifen reduces
      the risk of myocardial infarction. Thromboembolic events should be carefully
      monitored in trials of tamoxifen, particularly those of prophylactic treatment,
      in which tamoxifen is given to healthy women.

PMID- 7580639
TI  - Randomised controlled trial of laparoscopic versus open repair of inguinal
      hernia: early results.
AB  - OBJECTIVE: To establish the safety, short term outcome, and theatre costs of
      transabdominal laparoscopic repair of inguinal hernia performed as day surgery.
      DESIGN: Randomised controlled trial. The control operation was the two layer
      modified Maloney darn. SETTING: Teaching hospital and district general hospital.
      SUBJECTS: 125 men randomised to laparoscopic or open repair of inguinal hernia.
      OUTCOME MEASURES: Morbidity, postoperative pain and use of analgesics, quality of
      life, and theatre costs. Outcome was assessed by questionnaires administered to
      patients daily for 10 days and at six weeks postoperatively and by outpatient
      review at six weeks. Return to normal activity was assessed by questionnaire at
      three months. RESULTS: One vascular complication (2%) occurred in the group that
      had open repair. Seven complications (12%) including vessel injury and early
      recurrence arose in the group that had laparoscopic repair (difference in
      complication rate 10% (95% confidence interval 4% to 18%; P = 0.02). Pain scores
      and quality of life assessed by the short form 36 showed a significant benefit to
      the group that had laparoscopic repair in the early postoperative period. Return
      to normal activity was not significantly different between the two groups. Total
      theatre costs were higher in the group that had laparoscopic repair (mean cost
      for laparoscopic repair 850 pounds (622 pounds to 1078 pounds); mean cost for
      open repair 268 pounds (245 pounds to 292 pounds)). CONCLUSIONS: Because of the
      greater complication rate and higher theatre costs for laparoscopic repair and
      the patient outcome preferences expressed, the results of larger trials of
      clinical and cost effectiveness using recurrence as the primary outcome measure
      should be known before laparoscopic herniorrhaphy is widely adopted.

PMID- 7580640
TI  - Dietary underreporting by obese individuals--is it specific or non-specific?
AB  - OBJECTIVE: To examine the distribution of patterns of macronutrient density in
      relation to obesity. DESIGN: Cross sectional. SETTING: Denmark. SUBJECTS: 323 men
      and women aged 35-65 years, selected randomly from a larger population sample of
      Danish adults. MAIN OUTCOME MEASURE: Bias in dietary reporting of energy and
      protein intake in relation to percentage body fat, assessed by comparison of data
      from an interview on dietary intake with data estimated from 24 hour nitrogen
      output, validated by administering p-aminobenzoic acid, and estimated 24 hour
      energy expenditure. RESULTS: Degree of obesity was positively associated with
      underreporting of total energy and protein, whereas compared with total energy
      reported, protein was overreported by the obese subjects. CONCLUSION: Errors in
      dietary reporting of protein seem to occur disproportionately with respect to
      total energy, suggesting a differential reporting pattern of different foods.
      Although, on average, all subjects showed a greater underreporting of energy than
      of protein, this was most common in the obese subjects. Snack-type foods may be
      preferentially forgotten when obese people omit food items in dietary reporting.
      These results seem to agree with the general assumption that obese people tend to
      underreport fatty foods and foods rich in carbohydrates rather than underreport
      their total dietary intake. These results may have implications for the
      interpretation of studies of diet and comorbidities related to obesity.

PMID- 7580641
TI  - Prediction of acute mountain sickness.

PMID- 7580642
TI  - Specific therapeutic group age-sex related prescribing units (STAR-PUs):
      weightings for analysing general practices' prescribing in England.
AB  - OBJECTIVES: To derive cost comparators for prescribing by English general
      practitioners in eight specific therapeutic groups, based on age-sex related
      weightings, and to confirm, from a new dataset, earlier age-sex weightings for
      overall prescribing (ASTRO-PUs). DESIGN: Calculations based on one year's
      prescribing data from selected practices using AAH Meditel software, held on
      MediPlus by Intercontinental Medical Statistics (IMS, UK and Ireland), and
      research practices using VAMP software, held on the General Practice Research
      Database. SETTING: 112 English practices with 739,672 patients and 510 British
      practices with 3,126,570 patients. MAIN OUTCOME MEASURES: Cost based weightings
      for 18 age-sex groups and for temporary residents for eight leading specific
      therapeutic groups and for prescribing overall. RESULTS: The two datasets were
      similar in age distribution and in the way that prescription numbers were
      distributed by age-sex band in each therapeutic group. The cost based weightings
      for specific therapeutic groups showed great variation in the use of these groups
      for patients in different age-sex groups. When these weightings were applied to
      the prescribing of practices in two family health services authorities they
      differed in their power to predict prescribing costs: for cardiovascular and
      gastrointestinal drugs predictive power was particularly high; for drugs for
      infections it was particularly low, since these are widely used at all ages and
      for both sexes. Cost based weightings for overall prescribing derived from the
      IMS data were similar to those of the ASTRO-PU system even though they were
      derived by different methods from different datasets. CONCLUSIONS: The weightings
      (STAR-PUs) offer a sound basis for cost comparisons at the therapeutic group
      level. Cost-based weightings for overall prescribing derived from the IMS data
      were reassuringly similar to those of the existing ASTRO-PU system.

PMID- 7580643
TI  - Humanitarian responses to mass violence perpetrated against vulnerable
      populations.
AB  - This multidisciplinary review links three areas of legitimate inquiry for
      practitioners of medicine and public health. The first is occurrences of mass
      violence or genocide perpetrated against vulnerable populations, with a focus on
      the failure of national and international mechanisms to prevent or predict such
      violence. The second is evolving concepts of national sovereignty and an emerging
      framework in which the imperative to assist vulnerable populations supersedes a
      state's right to self determination. The last is how medical, public health, and
      other systems of surveillance and rapid assessment of mass violence can
      accelerate public awareness and facilitate structured, consistent political
      decision making to prevent mass violence and to provide international
      humanitarian assistance.

PMID- 7580644
TI  - Avoiding premature coronary deaths in Asians in Britain.

PMID- 7580646
TI  - Creating new criminals.

PMID- 7580645
TI  - European general practice.

PMID- 7580647
TI  - Mental health informatics and the rhythm of community care.

PMID- 7580648
TI  - Functional dysphonia.

PMID- 7580649
TI  - Infertility clinics show variation in success.

PMID- 7580650
TI  - US warns against early discharge of babies.

PMID- 7580651
TI  - German medical schools face serious reforms.

PMID- 7580652
TI  - Challenge is thrown to Europe's GPs.

PMID- 7580653
TI  - Nobel prize given for work on fruit flies.

PMID- 7580655
TI  - BUPA moves into general practice.

PMID- 7580654
TI  - Japan proposes settlement for tainted blood.

PMID- 7580656
TI  - Australia launches third AIDS strategy.

PMID- 7580657
TI  - Brazil takes steps to control tobacco.

PMID- 7580658
TI  - Rationality cut off in mobile phone row.

PMID- 7580659
TI  - Anticonvulsant drugs for management of pain: a systematic review.
AB  - OBJECTIVE: To determine effectiveness and adverse effects of anticonvulsant drugs
      in management of pain. DESIGN: Systematic review of randomised controlled trials
      of anticonvulsants for acute, chronic, or cancer pain identified by using
      Medline, by hand searching, by searching reference lists, and by contacting
      investigators. SUBJECTS: Between 1966 and February 1994, 37 reports were found;
      20 reports, of four anticonvulsants, were eligible. MAIN OUTCOME MEASURES:
      Numbers needed to treat were calculated for effectiveness, adverse effects, and
      drug related withdrawal from study. RESULTS: The only placebo controlled study in
      acute pain found no analgesic effect of sodium valproate. For treating trigeminal
      neuralgia, carbamazepine had a combined number needed to treat of 2.6 for
      effectiveness, 3.4 for adverse effects, and 24 for severe effects (withdrawal
      from study). For treating diabetic neuropathy, anticonvulsants had a combined
      number needed to treat of 2.5 for effectiveness, 3.1 for adverse effects, and 20
      for severe effects. For migraine prophylaxis, anticonvulsants had a combined
      number needed to treat of 1.6 for effectiveness, 2.4 for adverse effects, and 39
      for severe effects. Phenytoin had no effect on the irritable bowel syndrome, and
      carbamazepine had little effect on pain after stroke. Clonazepam was effective in
      one study for temporomandibular joint dysfunction. No study compared one
      anticonvulsant with another. CONCLUSIONS: Anticonvulsants were effective for
      trigeminal neuralgia and diabetic neuropathy and for migraine prophylaxis. Minor
      adverse effects occurred as often as benefit.

PMID- 7580660
TI  - Home environment and severe asthma in adolescence: a population based case
      control study.
AB  - OBJECTIVE: To investigate the effects of the home environment on the risk of
      severe asthma during adolescence. DESIGN: A questionnaire based case-control
      study drawn from a cross sectional survey of allergic diseases among secondary
      school pupils in Sheffield in 1991. SUBJECTS: 763 children whose parents had
      reported that over the previous 12 months they had suffered either 12 or more
      wheezing attacks or a speech limiting attack of wheeze. A further 763 children
      were frequency matched for age and school class to act as controls. Analysis was
      restricted to 486 affected children and 475 others born between 1975 and 1980 who
      had lived at their present address for more than three years. RESULTS:
      Independent associations with severe wheeze were seen for non-feather bedding,
      especially foam pillows (odds ratio 2.78; 95% confidence interval 1.89 to 4.17),
      and the ownership of furry pets now (1.51; 1.04 to 2.20) and at birth (1.70; 1.20
      to 2.40). These estimates were derived from subjects whose parents denied making
      changes in the bedroom or avoiding having a pet because of allergy. Parental
      smoking, use of gas for cooking, age of mattress, and mould growth in the child's
      bedroom were not significantly associated with wheezing. CONCLUSIONS: Either our
      study questionnaire failed to detect the avoidance or removal of feather bedding
      by allergic families or there is some undetermined hazard related to foam
      pillows. Synthetic bedding and furry pets were both widespread in this population
      and may represent remediable causes of childhood asthma.

PMID- 7580661
TI  - Evidence based purchasing: understanding results of clinical trials and
      systematic reviews.
AB  - OBJECTIVE: To assess whether the way in which the results of a randomised
      controlled trial and a systematic review are presented influences health policy
      decisions. DESIGN: A postal questionnaire to all members of a health authority
      within one regional health authority. SETTING: Anglia and Oxford regional health
      authorities. SUBJECTS: 182 executive and non-executive members of 13 health
      authorities, family health services authorities, or health commissions. MAIN
      OUTCOME MEASURES: The average score from all health authority members in terms of
      their willingness to fund a mammography programme or cardiac rehabilitation
      programme according to four different ways of presenting the same results of
      research evidence--namely, as a relative risk reduction, absolute risk reduction,
      proportion of event free patients, or as the number of patients needed to be
      treated to prevent an adverse event. RESULTS: The willingness to fund either
      programme was significantly influenced by the way in which data were presented.
      Results of both programmes when expressed as relative risk reductions produced
      significantly higher scores when compared with other methods (P < 0.05). The
      difference was more extreme for mammography, for which the outcome condition is
      rarer. CONCLUSIONS: The method of reporting trial results has a considerable
      influence on the health policy decisions made by health authority members.

PMID- 7580662
TI  - Attitudes of consultant physicians to the Calman proposals: a questionnaire
      survey. North West Thames Diabetes and Endocrinology Specialist Group.
AB  - OBJECTIVE: To determine the views of a large and representative group of
      consultant physicians on the Calman proposals, in which acute general medical
      services will change from being primarily consultant led to consultant provided.
      DESIGN: Postal questionnaires. SUBJECTS: All 236 consultant physicians in acute
      hospitals in North West and South West Thames regions. RESULTS: Replies were
      received from 179 (76%). One hundred and thirty seven (77%) indicated that they
      would not resume emergency residential duties, and 126 (71%) indicated that they
      would probably withdraw from general medical duties under these circumstances.
      One hundred and twenty six (70%) and 137 (77%) had not inserted a central venous
      line or temporary pacemaker, respectively, within the previous five years. Of 157
      answering a question on the impact of the Calman proposals on the quality of
      patient services, 125 considered that it would be detrimental, and only 18 (11%)
      thought that it would be beneficial. CONCLUSION: Most consultant physicians are
      not prepared to resume emergency duties and could not do so without retraining in
      practical procedures. There is widespread antagonism to the Calman proposals, and
      most physicians consider that their impact on the quality of patient services
      will be detrimental.

PMID- 7580663
TI  - Randomised controlled trial assessing effectiveness of health education leaflets
      in reducing incidence of sunburn.

PMID- 7580664
TI  - Prevalence of urinary and faecal incontinence in hospitals and residential and
      nursing homes for older people.

PMID- 7580665
TI  - Contamination with blood during management of epistaxis.

PMID- 7580666
TI  - Using information from asthma patients: a trial of information feedback in
      primary care.
AB  - OBJECTIVE: To test the effects of feedback of information about patients' asthma
      to primary care teams. DESIGN: Patients' reports of morbidity, use of health
      services, and drug use on questionnaire was given to primary care teams.
      Randomised controlled trial with general practices as the subject of the
      intervention was used to test effectiveness of supplying information. SETTING:
      Primary care in district health authority, London. SUBJECTS: 23 general
      practices, each of which notified at least 20 asthmatic patients aged 15-60 years
      for each principal. Practices were randomly allocated to an invention group
      (receiving feedback of information on control of asthma) or a control group (no
      feedback). INTERVENTION: Information on cards inserted in patients' medical
      records; booklet copies of information for team members; formal presentation to
      primary care teams; poster displays of data on patients in each practice. MAIN
      OUTCOME MEASURES: Type and frequency of asthma symptoms, use of health services,
      use of asthma drugs. RESULTS: Reported morbidity at entry to the study was
      substantial: 45% (818) patients reported breathlessness at least once a week.
      Less than half these patients were using inhaled steroids regularly. Intervention
      and control groups did not differ in practice or patient characteristics on entry
      to the study. In spite of the potential for improvement no differences were
      observed between the two practice groups at the end of the study--for example,
      breathlessness at least once a week in last six months was experienced by 36% in
      intervention group v 35% in control group (t = -0.27, P < 0.79); surgery
      attendance in last six months by 48% v 48% (t = -0.05, P < 0.96); regular use of
      inhaled steroids by 60% v 58% (t = 0.51, P < 0.62). CONCLUSION: Feedback to
      general practitioners of information about patients' asthma does not on its own
      lead to change in the outcome of clinical care.

PMID- 7580667
TI  - Moving house: a risk factor for the development of childhood asthma?

PMID- 7580669
TI  - Setting priorities for research and development in the NHS: a case study on the
      interface between primary and secondary care.
AB  - Since 1991 the NHS has attempted to identify and prioritise its needs for
      research and development in a systematic manner. This has not been done before
      and there is little evidence on which to draw. Multidisciplinary expert groups
      have identified priorities in different topics using explicit criteria and after
      widespread consultation within the NHS and research community to identify
      pressing problems and opportunities for research. This paper focuses on a review
      completed in 1993 to identify research and development priorities for the NHS in
      relation to the interface between primary and secondary care. The review covered
      several recent developments which require evaluation. The authors describe the
      process used to identify research and development priorities in this complex
      subject and examine the strengths and weaknesses of the approach. This case study
      should help to stimulate a wider debate on methods of identifying priorities,
      particularly those using participatory approaches, in research and non-research
      contexts.

PMID- 7580670
TI  - Commissioning a national programme of research and development on the interface
      between primary and secondary care.
AB  - The first call for applications to the NHS research and development programme on
      the interface between primary and secondary care was advertised in February 1994.
      A total of 674 outline proposals were submitted and 54 (8%) secured funding.
      Projects have been commissioned in 16 of the 21 priority areas and around 6m
      pounds has been committed. Analysis shows that multidisciplinary applications are
      more likely to be funded and that the odds for a successful application are on
      average nearly doubled for each discipline represented up to five. A survey of
      applicants and peer reviewers found satisfaction with much of the commissioning
      process, but peer review and feedback were subject to criticism, particularly by
      unsuccessful applicants. The programme shows that it is possible to commission a
      large number of projects in an innovative area of research and development and
      has identified refinements that will further increase the efficiency and
      acceptability of the process.

PMID- 7580668
TI  - The myth of maternal transmission of spongiform encephalopathy.
AB  - It has long been accepted that the pattern of occurrence of scrapie--the form of
      spongiform encephalopathy associated with sheep--is determined mainly by maternal
      transmission, and this view has had a profound influence on policy decisions in
      the control of bovine spongiform encephalopathy and on public concern over the
      risk to human health form this disease. The occurrence of maternal transmission
      is, however, not predicted by modern knowledge of the aetiology of spongiform
      encephalopathy, and even though claims of maternal transmission have been
      reiterated frequently in the literature, re-examination of the source data
      reveals that these data are extremely scanty, unreplicated, and probably subject
      to ascertainment bias. The probability of maternal transmission of spongiform
      encephalopathy in any species should be viewed with the greatest scepticism.

PMID- 7580671
TI  - The risks of delay in diagnosis of breathlessness in pregnancy.

PMID- 7580672
TI  - Female genital mutilation. Cultural knowledge is the key to understanding.

PMID- 7580673
TI  - Female genital mutilation. Professionals should not collude with abusive systems.

PMID- 7580674
TI  - Female genital mutilation. Should be abolished.

PMID- 7580675
TI  - Dangers of cocaine and adrenaline paste. Accurate measurement of dose and
      patience are important.

PMID- 7580676
TI  - Dangers of cocaine and adrenaline paste. Combination is still widely used.

PMID- 7580677
TI  - Dangers of cocaine and adrenaline paste. Exceeding the recommended dose may have
      serious sequelae.

PMID- 7580678
TI  - Dangers of cocaine and adrenaline paste. Other aspects of anaesthetic technique
      may have added to danger.

PMID- 7580679
TI  - Inserting central venous catheters. Open technique has lower evidence of
      complications.

PMID- 7580680
TI  - Inserting central venous catheters. Case for angiographically guided placement is
      not proved.

PMID- 7580681
TI  - Inserting central venous catheters. Difficulties are rare and do not correlate
      with lifespan of catheter.

PMID- 7580682
TI  - Inserting central venous catheters. Line should not enter the heart.

PMID- 7580683
TI  - Inserting central venous catheters. Operating theatre is better back up than
      venography.

PMID- 7580684
TI  - Inserting central venous catheters. Surgical cutdown technique should not be
      abandoned.

PMID- 7580685
TI  - Treatment of gall stones. Non-surgical treatments should not be dismissed.

PMID- 7580686
TI  - Qualitative thesis explored social dislocation and health.

PMID- 7580687
TI  - Treatment of gall stones. Rate of surgery for gall stones is increasing.

PMID- 7580688
TI  - Illness behaviour in the chronic fatigue syndrome and multiple sclerosis. Choice
      of multiple sclerosis as comparison condition was inappropriate.

PMID- 7580689
TI  - Illness behaviour in the chronic fatigue syndrome and multiple sclerosis.
      Disentangling common characteristics is not so easy.

PMID- 7580690
TI  - Junior doctors' hours. Committee response was ignorant.

PMID- 7580691
TI  - Medical firms should be retained.

PMID- 7580692
TI  - Junior doctors' hours. Long hours are needed.

PMID- 7580693
TI  - Junior doctors' hours. Committee lacks "shop floor" support.

PMID- 7580694
TI  - Junior doctors' hours. Wong should join Junior Doctors' Committee.

PMID- 7580695
TI  - Junior doctors' hours. Wong was right.

PMID- 7580696
TI  - Terms and conditions of service for new specialist registrar grade are not yet
      established.

PMID- 7580697
TI  - Advising women on which pill to take.

PMID- 7580698
TI  - Third generation oral contraceptive pills.

PMID- 7580699
TI  - Endarterectomy for asymptomatic carotid artery stenosis.

PMID- 7580700
TI  - Hunger strikes.

PMID- 7580702
TI  - US proposes radical reform of Medicare.

PMID- 7580703
TI  - Effect of air pollution on asthma is "small".

PMID- 7580704
TI  - Russia tries to reduce irradiation deaths.

PMID- 7580701
TI  - Management of blood loss in Jehovah's Witnesses.

PMID- 7580705
TI  - Community care for severely disabled people on low incomes.
AB  - OBJECTIVE: To examine the volume and distribution of formal and informal care
      received by severely disabled adults living at home in the community on low
      incomes according to type of disease. DESIGN: Analysis of computerised reports
      from social workers which include information on disabling conditions and on the
      weekly hours of care at home from formal and informal sources. SUBJECTS: 1298
      severely disabled people aged 16 to 98 who received financial assistance from the
      Independent Living Fund in 1991-2. RESULTS: Over half (733; 56.6% (53.8 to 59.2))
      of the sample were completely unable to perform five or more of the basic
      activities of daily living. On average the whole sample received 6.8 (6.1 to 7.6)
      hours of care at home a week from formal sources and 64.2 (62.4 to 65.9) hours
      from informal sources. In seven out of 14 disease groups, less than half in each
      group received any formal help at home. There were large differences in the
      volume of formal care within groups. In most cases no significant differences
      were found within diagnostic groups between those receiving care at home from
      district health authorities or local authorities, or both, and those who received
      no help at home with regard to age, dependency score, and duration of disability.
      Weekly hours of informal care were an important determinant of who received
      formal help in nine out of 14 groups. CONCLUSIONS: The amount of care received at
      home by low income, severely disabled people from formal sources differs across
      and within diagnostic groups. The fact that the variation was not systematically
      related to age, dependency, or duration suggests that the existing distribution
      of community care resources needs to be examined. Weekly hours of informal care
      and diagnosis seem to affect the volume and type of care received. The methods by
      which people in need of assistance receive help merit further investigation.

PMID- 7580706
TI  - Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E
      concentrations: a four year follow up study in men.
AB  - OBJECTIVE: To investigate whether low vitamin E status is a risk factor for
      incident non-insulin dependent diabetes mellitus. DESIGN: Population based follow
      up study with diabetes assessed at baseline and at four years. SETTING: Eastern
      Finland. SUBJECTS: Random sample of 944 men aged 42-60 who had no diabetes at the
      baseline examination. INTERVENTION: Oral glucose tolerance test at four year
      follow up. MAIN OUTCOME MEASURES: A man was defined diabetic if he had either (a)
      a fasting blood glucose concentration > or = 6.7 mmol/l, or (b) a blood glucose
      concentration > or = 10.0 mmol/l two hours after a glucose load, or (c) a
      clinical diagnosis of diabetes with either dietary, oral, or insulin treatment.
      RESULTS: 45 men developed diabetes during the follow up period. In a multivariate
      logistic regression model including the strongest predictors of diabetes, a low
      lipid standardised plasma vitamin E (below median) concentration was associated
      with a 3.9-fold (95% confidence interval 1.8-fold to 8.6-fold) risk of incident
      diabetes. A decrement of 1 mumol/l of uncategorised unstandardised vitamin E
      concentration was associated with an increment of 22% in the risk of diabetes
      when allowing for the strongest other risk factors as well as serum low density
      lipoprotein cholesterol and triglyceride concentrations. CONCLUSIONS: There was a
      strong independent association between low vitamin E status before follow up and
      an excess risk of diabetes at four years. This supports the theory that free
      radical stress has a role in the causation of non-insulin dependent diabetes
      mellitus.

PMID- 7580707
TI  - A randomised trial of three methods of giving information about prenatal testing.
AB  - OBJECTIVE: To test the effect of extra non-directive information about prenatal
      testing, given individually or in a class. SETTING: Antenatal clinics in a
      district general hospital and a university hospital. DESIGN: Randomised
      controlled trial; participants allocated to control group or offer of extra
      information individually or in class. SUBJECTS: 1691 women booking antenatal care
      before 15 weeks' gestation. INTERVENTIONS: All participants received the usual
      information about prenatal tests from hospital staff. Individual participants
      were offered a separate session with a research midwife in which prenatal
      screening was described in detail. Class participants were offered the same extra
      information in an early prenatal class. MAIN OUTCOME MEASURES: Attendance at
      extra information sessions; uptake rates of prenatal tests; levels of anxiety,
      understanding, and satisfaction with decisions. RESULTS: Attendance at classes
      was lower than at individual sessions (adjusted odds ratio 0.45; 95% confidence
      interval 0.35 to 0.58). Ultrasonography was almost universally accepted (99%) and
      was not affected by either intervention. Uptake of cystic fibrosis testing, high
      in controls (79%), was lowered in the individual group (0.44; 0.20 to 0.97) and
      classes (0.39; 0.18 to 0.86). Uptake of screening for Down's syndrome, already
      low (34%) in controls, was not further depressed by extra information in classes
      (0.99; 0.70 to 1.39) and was slightly higher in the individual group (1.45; 1.04
      to 2.02). Women offered extra information had improved understanding and were
      more satisfied with information received; satisfaction with decisions about
      prenatal testing was unchanged. The offer of individual information reduced
      anxiety later in pregnancy. CONCLUSIONS: Ultrasonography is valued for non
      medical reasons and chosen even by fully informed people who eschew prenatal
      diagnosis. The offer of extra information has no overall adverse effects on
      anxiety and reduces uptake of blood tests when background uptake rate is high
      (but not when it is already low). High uptake of prenatal blood tests suggests
      compliant behaviour and need for more information.

PMID- 7580709
TI  - Prison rites: starting to inject inside.

PMID- 7580708
TI  - Sensitivity and specificity of photography and direct ophthalmoscopy in screening
      for sight threatening eye disease: the Liverpool Diabetic Eye Study.
AB  - OBJECTIVE: To evaluate different methods for community based screening for sight
      threatening diabetic eye disease. DESIGN: Prospective study. SETTING: Mobile
      screening unit visiting inner city community clinics; hospital assessment clinic
      (tertiary centre). SUBJECTS: 395 diabetic patients registered with four general
      practices in an inner city location. INTERVENTIONS: Community based photography
      with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced
      ophthalmologist, both compared with reference standard of slit lamp biomicroscopy
      by a consultant specialist in medical retinal disease. MAIN OUTCOME MEASURES:
      Sensitivity and specificity of screening method and prevalence of sight
      threatening diabetic eye disease (moderate preproliferative retinopathy,
      circinate maculopathy, exudate within 1 disc diameter of fixation, other diabetes
      related eye disease). RESULTS: 358 subjects underwent photography, 326 attended
      hospital clinic for ophthalmoscopy, and six were ungradable on photographs and
      biomicroscopy, leaving 320 for analysis. Of these 295 (91%) attended clinic
      within four months of photography. Sensitivity of detection of eye disease by
      photography was 89% (95% confidence interval 80% to 98%), significantly better
      than for direct ophthalmoscopy (65% (51% to 79%)). Analysis of patients with
      false negative results indicated possible improvement of photographic sensitivity
      to 93% by addition of stereoscopic macular pair photographs. Specificity of
      detection of sight threatening eye disease was 86% (82% to 90%) for photography
      and 97% (95% to 99%) for direct ophthalmoscopy. CONCLUSIONS: Since high
      sensitivity is essential for an effective screening programme, a photographic
      method should be considered as preferred option in national, community based
      screening programmes. Even in the hands of an experienced ophthalmologist, direct
      ophthalmoscopy is limited by weaknesses inherent to the instrument.

PMID- 7580710
TI  - Patients' views of priority setting in health care: an interview survey in one
      practice.
AB  - OBJECTIVES: To explore the assumptions underlying consumers' responses to
      questions of resource priorities in the NHS. DESIGN: Qualitative analysis of semi
      structured interviews with a heterogeneous sample of 16 patients drawn from a
      general practice. RESULTS: Interviewees were not persuaded that they had a
      legitimate role to play in the prioritisation of services. They supported the
      principle of equity and were reluctant to use their own personal needs as a basis
      for resource allocation; instead they argued from what they perceived to be the
      needs of others. CONCLUSIONS: Paradoxically, surveys of consumers' views on
      health care priorities probably do not elicit the personal ideas of respondents
      but tap into a more general ideological position closer to an earlier
      collectivist notion of health care.

PMID- 7580711
TI  - Body fat distribution before pregnancy and gestational diabetes: findings from
      coronary artery risk development in young adults (CARDIA) study.

PMID- 7580712
TI  - Management of acoustic neuroma.

PMID- 7580713
TI  - Estimating sample sizes for binary, ordered categorical, and continuous outcomes
      in two group comparisons.
AB  - Sample size calculations are now mandatory for many research protocols, but the
      ones useful in common situations are not all easily accessible. This paper
      outlines the ways of calculating sample sizes in two group studies for binary,
      ordered categorical, and continuous outcomes. Formulas and worked examples are
      given. Maximum power is usually achieved by having equal numbers in the two
      groups. However, this is not always possible and calculations for unequal group
      sizes are given.

PMID- 7580714
TI  - ABC of medical computing. Adaptive computer technology.

PMID- 7580715
TI  - Counting the costs of children's smoking.
AB  - The recent publication of the 1994 OPCS survey of smoking among secondary school
      children confirmed that the Health of the Nation target for children's smoking (a
      reduction in regular smoking from 8% in 1988 to less than 6% in 1994) has not
      been achieved. In 1994, 12% of English schoolchildren aged 11-15 were regular
      smokers (as were 12% in Scotland, 9% in Wales, and 12.5% in Northern Ireland). In
      1994 the government spent around 10 million pounds on initiatives to prevent
      smoking, but received around 8643 million pounds in tax receipts from tobacco
      sales, about 108 million pounds of which was tax receipts from the illegal sale
      of cigarettes to children under 16 years old. The tobacco industry spent an
      estimated 100 million pounds on promotional activities. Improving current trends
      in children's smoking by the year 2000 will require decisive action by the
      government. The government should legislate to ban tobacco advertising and should
      use the 108 million pounds taken each year in taxes from smoking children to fund
      smoking cessation and prevention initiatives.

PMID- 7580716
TI  - Consulting the public about health service priorities.
AB  - Consulting the public is an important component of commissioning health services.
      Somerset Health Authority has devised a method of consultation using eight focus
      groups meeting three times a year. Each group consists of 12 people, and together
      the groups are demographically representative of Somerset's population. The
      groups are asked about issues that are concerning the health authority, and their
      views have influenced health authority decisions. Each group is given some
      background information before the meeting, together with more information at the
      meeting. The discussions are tape recorded and analysed for qualitative
      information, but the groups are also asked to score certain priorities. The
      groups have been found to be representative, valid, and focused on community
      rather than individual values. Health authorities wanting to know the values
      people attach to health services should adopt this qualitative approach to
      consultation.

PMID- 7580717
TI  - Data from transnational study of oral contraceptives have been misused.

PMID- 7580718
TI  - Medical aspects of fitness to drive. Unfit patients are a common and difficult
      problem.

PMID- 7580719
TI  - Medical aspects of fitness to drive. Enabling patients to drive is also
      important.

PMID- 7580720
TI  - Medical aspects of fitness to drive. Assessments should be independent.

PMID- 7580721
TI  - Medical aspects of fitness to drive. Rigid rules for hypomanic patients are
      unfair.

PMID- 7580722
TI  - Sexual behaviour of men. Review mis-stated prevalence of anal intercourse.

PMID- 7580723
TI  - Sexual behaviour of men. Survey shows unprotected sex is a common behaviour in
      bisexual men.

PMID- 7580724
TI  - Obtaining insurance should not depend on mechanism of diagnosis tests.

PMID- 7580725
TI  - Protecting children in cars from tobacco smoke.

PMID- 7580726
TI  - Effects of helicopter service on survival after trauma. Service is part of a
      continuum of care.

PMID- 7580727
TI  - Effects of helicopter service on survival after trauma. Design of study
      predisposed to type II error.

PMID- 7580728
TI  - Effects of helicopter service on survival after trauma. Helicopters do not care
      for patients.

PMID- 7580729
TI  - Effects of helicopter service on survival after trauma. Miscalculation
      exaggerated benefits.

PMID- 7580730
TI  - Effects of helicopter service on survival after trauma. Dramatic management of
      trauma may be counter productive.

PMID- 7580731
TI  - Mortality associated with wines, beers, and spirits. Australian data suggest that
      choice of beverage relates to lifestyle and personality.

PMID- 7580732
TI  - Mortality associated with wines, beers, and spirits. Inappropriate groups were
      used to calculate relative risk.

PMID- 7580733
TI  - Mortality associated with wines, beers, and spirits. Binge drinkers should have
      been identified separately.

PMID- 7580734
TI  - Mortality associated with wines, beers, and spirits. Risk function had peculiar
      properties.

PMID- 7580735
TI  - Mortality associated with wines, beers, and spirits. Study confounded by lack of
      correction for social class.

PMID- 7580736
TI  - Performance indicators for general practice. Emphasis is changing from quality
      assurance to continuous quality improvement.

PMID- 7580738
TI  - Performance indicators for general practice. Inadequate smears are not always due
      to poor technique.

PMID- 7580737
TI  - Factors influencing participation in audit.

PMID- 7580739
TI  - Health authorities use panels to gather public opinion.

PMID- 7580740
TI  - Analgesic effects of sucrose were known to the prophet.

PMID- 7580741
TI  - BMJ should review its policy on reprints.

PMID- 7580742
TI  - Concern about "lookback" exercise for hepatitis C.

PMID- 7580743
TI  - [Changes in the activity of an epileptogenic focus in the rat hippocampus under
      the influence of bemitil].
AB  - Experiments performed on male rats with chronically implanted electrochemotrodes
      showed bemitil (12.5 and 25.0 mg/kg, intra-abdominally, 24 h prior to the locus
      creation) suppresses he pathological activity of (100 ED) epileptogenic locus
      induced by he sodium salt of penicillin in the hippocampus of the animals.
      Probable mechanisms of antiepileptic action of bemitil are considered.

PMID- 7580745
TI  - [The correlation of the electroencephalographic and clinical effects of
      benzodiazepine tranquilizers in patients with mental disorders at the neurotic
      level].

PMID- 7580744
TI  - [The effects of preparations that influence the brain monoaminergic systems in
      pain syndromes].

PMID- 7580746
TI  - [The cerebral blood circulation during hypokinesia under the influence of
      hypercapnia, hypotonia, GABA and neurosensory stimulation].
AB  - We studied the formation of vasomotor reflexes in hypokinesia and responses of
      the brain vessels to the action of GABA, hypotension, and hypercapnia. We found
      that the response of the brain vessels to GABA is delayed and the mechanisms
      which supported an adequate cerebral vasculation are distorted in hypotension. At
      the same time the disturbance of the reflectory reaction of the brain vessels in
      the course of forming the vasomotor reflexes and the absence of significant
      changes in response to GABA were noticed. The capability of GABA of inhibiting
      cerebral blood circulation arising in hypokinesia is shown.

PMID- 7580747
TI  - [An experimental study of the pharmacological activity of opiate receptor ligands
      on models of adrenaline-induced arrhythmias].
AB  - The influence of intracerebroventricular injection of opioid peptides on the
      incidence and severity of ventricular arrhythmia induced by intravenous
      administration of epinephrine was studied. It was found that DAGO, a selective mu
      agonist, and DADLE, a nonselective delta-agonist, reduce the incidence and
      severity of cardiac arrhythmia in rats. On the contrary, DSLET, a selective delta
      agonist, and Dynorphin A 1-13 (kappa-agonist), potentiates epinephrine-induced
      arrhythmias. beta-Endorphin do not affect the arrhythmia. The activation of
      cerebral mu-opioid receptors is shown to prevent the appearance of arrhythmia. On
      the contrary, the activation of delta- and kappa-receptors induces the appearance
      of arrhythmia.

PMID- 7580748
TI  - [The effect of damage to the hypothalamic suprachiasmatic nuclei in rats on the
      restructuring of the dynamic indices of the cardiointervalogram induced by
      propranolol].
AB  - Daily variations in the heart rate were studied. Chronic treatment with
      propranolol attenuated the sympathetic tone only at night and promoted acrophase
      in the morning. The complete lesion of suprachiasmatic nuclei balanced the
      circadian rhythm of the heart rate variability and the effect of drug.

PMID- 7580749
TI  - [Means for the pharmacological regulation of the cerebral blood circulation].

PMID- 7580750
TI  - [The role of protein kinase C and muscarinic cholinoreceptors in vasopressin
      stimulated water transport].
AB  - The role of protein kinase C (PKC) in the control of vasopressin-stimulated water
      transport in the frog urinary bladder and its modulation by M2-agonist
      oxotremorine has been studied. Using the PKC inhibitor, staurosporine we showed
      that PKC in the region pf the basal membrane suppressed vasopressin-stimulated
      water transport, whereas PKC in the apical region potentiated this transport. It
      was also found that from the two types of oxotremorine action on stimulated water
      transport determined by its concentration only inhibition is mediated through
      PKC.

PMID- 7580752
TI  - [The stimulating effect of sialic acid on the processes of postradiation
      hemopoietic regeneration].
AB  - The possibility of stimulating hemopoiesis inhibited by irradiation with N
      acetylneuraminic acid (N-ANA) and the mechanisms of this stimulating effect are
      considered. A 3-fold N-ANA injection (total dose 150 mg/kg) on days 3, 4, and 5
      after irradiation mainly promote the activation of erythropoiesis in the bone
      marrow. A reliable increase in the amount of erythrokaryocytes in the bone marrow
      and erythroid colony formation from erythroid precursors (CFU-E) were observed in
      mice CBA irradiated in a dose of 2.0 g and then received N-ANA. A rise in
      erythropoietic activity production by bone marrow cells testified that elevation
      of hemopoiesis inducing microenvironment function is the base of stimulating
      effect of N-ANA on hemopoiesis.

PMID- 7580751
TI  - [The erythrocytic pathway of the metabolic transformations of sex hormones].

PMID- 7580754
TI  - [The effect of tetrachloromethane and ethanol on the release by rat splenocytes
      of immunomodulating factors].
AB  - In combined introduction tetrachloromethane (TCM) and ethanol the spleen cells
      secrete both immunostimulating agent with a molecular mass (MM) of 10 - 25 kD and
      immunosuppressing agents with MM > 100 kD. Sticking and nonsticking to the glass
      splenocytes of the animal affected by TCM and ethanol, excrete, respectively, the
      immunostimulating or immunosuppressing agents to the supernatant liquid of the
      splenocytes.

PMID- 7580753
TI  - [The effect of pyrimidines, levamisole and prodigiozan on the antigen-specific
      regulation of delayed hypersensitivity in relation to the age and strain of the
      mice].
AB  - The effect of pyrimidine, levamizol, and prodigiozan on the retarded
      hypersensitivity (RH) was studied on a model of adoptive transfer of the
      splenocytes from donors of different ages to young syngeneic recipients.
      Splenocytes from CBA and BALB/c suckers, receiving pyrimidine, activate the RH
      suppression. Levamizol and prodigiozan exert the same effect on BALB/c mice and
      inhibit the RH suppression in CBA mice. In mature CBA mice these preparations
      potentiate HST. The splenocytes from young and aged BALB/c donors receiving the
      preparations oppositely induce the RH recipients.

PMID- 7580755
TI  - [The relationship between antipyrine kinetics, the seromucoid content and the
      xanthine oxidase activity in the plasma of rats with acute and chronic
      inflammation].
AB  - The relationship between changes in seromucoid levels, xanthine oxidase activity
      in plasma, and drug metabolism in rats with turpentine-induced inflammation and
      adjuvant-induced arthritis was studied. For antipyrine, systemic clearance
      decreased, the volume distribution remained the same, and the half-life increased
      in turpentine- and adjuvant-treated rats. In both cases seromucoid level and
      xanthine oxidase activity in plasma increased. Treatment of rats with
      dexamehasone before turpentine-induced inflammation raised the level of
      seromucoid. However, dexamehasone treatment of rats with adjuvant disease
      significantly decreased the level of seromucoid. Moreover, dexamehasone
      administration did not significantly protect against the effects of inflammation
      on the hepatic microsomal drug-metabolizing enzyme system and activity of
      xanthine oxidase in plasma. Thus, pharmacokinetics of different drugs can
      significantly change in some types of inflammation in animals and humans,
      particularly by dexamehasone administration.

PMID- 7580756
TI  - [The effect of physical loading on the pharmacokinetics of drugs].
AB  - In model experiments on rats performed with the use of radioindication assay and
      the HPLG method it was shown that the total level of cholinolytics, pediphen (20
      mg/kg) and peniphin (6 mg/kg) reliably decreases in plasma after oral
      administration during physical exercise (method of free swimming under loading).
      At the same time the intramuscular injection of pediphen (2 mg/kg) and peniphin
      (0.6 mg/kg) induce a reliable increase in the concentration of cholinolytics in
      plasma under the influence of physical exercise. The mechanism of observed
      changes in pharmacokinetics of neurotropic drugs are discussed. The results of
      this study may be used in therapy to optimize doses of cholinolytic drugs in
      conditions of physical and/or locomotor activity.

PMID- 7580757
TI  - [The central component in the mechanism of the analgesic action of nonsteroidal
      anti-inflammatory agents].

PMID- 7580758
TI  - [The effect of cardiovascular agents on the hemostatic system in myocardial
      ischemia].

PMID- 7580759
TI  - [The culture of renal epithelial cells: the physiological and pharmacological
      aspects].
AB  - Cultured renal epithelial cells are widely used to examine renal functions and
      drug control, as well as renal transport of drugs and other xenobiotics. This
      review is aimed at attracting attention to the techniques of cell strains that
      show the properties typical of a proximal or distal parts of a nephron. It
      considers the existing primary and identified cultures and the most important
      recent experimental findings.

PMID- 7580760
TI  - [Preparations affecting arachidonic acid metabolism in the thrombocytes in the
      treatment of ischemic heart disease].

PMID- 7580761
TI  - [The effect of bromantane on the dopamin- and serotoninergic systems of the rat
      brain].
AB  - The effect of acute and chronic administration (50 mg/kg, p.o.) of a new
      immunostimulator, bromantan exhibiting psychostimulant features on the content of
      NE, DA and 5-HT, and their metabolites are studied. Bromantan induced a
      significant increase in the 5-HT and 5-HIAA content in the frontal cortex and
      delayed an increase in their content in subcortical brain regions. A stable
      decrease in the 5-HT and 5-HIAA levels in the cerebellum is observed. The drug
      also affected the DA parameters of the brain thus suggesting an important role of
      dopaminergic system in the mechanism of pharmacological effects of the drug.

PMID- 7580762
TI  - Modulation of sensitivity to hyperbaric oxygen by CO2 in newborn rats.
AB  - We examined the modifying effects of CO2 on the CNS and pulmonary manifestations
      of hyperbaric oxygenation (HBO) in newborn rats. Four- to seven-day-old rats were
      exposed to HBO with inspired PCO2 (PICO2) of approximately 0, 60, 90, 140, 190,
      and 380 mmHg at a total pressure of 5 atm abs. The PCO2 values studied
      corresponded with 0, 8, 12, 18, 25, and 50 kPa, respectively, at a total pressure
      of 507 kPa. The O2-CO2 exposures lasted for 2-8 h. Hypercapnia at PICO2 of 60 and
      90 mmHg with HBO produced extensive pulmonary damage with a high post
      decompression mortality, compared to HBO alone. In contrast, PICO2 at the
      anesthetic levels of 140 and 190 mmHg attenuated the visible pulmonary and
      neurologic manifestations of O2 toxicity, and significantly reduced post
      decompression mortality, compared to moderate hypercapnia of 60-90 mmHg.
      Supercapnia, at PICO2 of 380 mmHg, with HBO also produced no visible neurologic
      effect, but it caused an early apnea with severe pulmonary damage. These data
      indicate unique and dose-dependent cerebral and pulmonary responses to hyperoxic
      hypercapnia in newborn rats. It is speculated that anesthetic levels of
      hypercapnia may be utilized to improve tissue oxygenation during O2 therapy in
      newborns, without increasing the risk of pulmonary and CNS O2 poisoning.

PMID- 7580763
TI  - Decreased protein synthesis during dry saturation diving.
AB  - Changes in metabolism during saturation dives have been reported; however, these
      changes have not been well defined. This study was conducted to determine the
      effect of saturation diving on protein metabolism. Whole body protein synthesis
      was measured by the ammonia and urea endpoint methods, following a single oral
      dose of 15N-glycine in 11 Navy divers 33.9 +/- 1.9 yr of age. The divers were fed
      a controlled diet throughout the three trials. Trial I was on the surface, and
      trials II and III were during dry saturation dives at 0.56 MPa. The protein
      synthesis results in gram protein per kilogram lean body mass per day, least
      square mean +/- SD: [formula: see text]. Under the conditions of this series of
      dry saturation dives, protein synthesis was depressed by up to 30-50% for the
      urea and ammonia endpoint methods, respectively. An estimate of liver protein
      synthesis was made by measuring the incorporation of the 15N label into plasma
      fibrinogen. The 15N enrichment of fibrinogen glycine and the hippurate precursor
      for fibrinogen were decreased significantly. This dramatic decrease in protein
      synthesis was observed despite positive nitrogen balance in these divers.
      Although further investigation is needed to elucidate the mechanism, the decrease
      in the incorporation of 15N glycine into fibrinogen suggests alteration in liver
      nitrogen metabolism at 0.56 MPa.

PMID- 7580764
TI  - Brainstem auditory evoked potentials during a helium-oxygen saturation dive to
      450 meters of seawater.
AB  - When divers are exposed to extreme atmospheric pressures they may exhibit
      symptoms of the high pressure nervous syndrome (HPNS). Although clinical HPNS
      symptoms are well described, little is known about the underlying
      pathophysiologic mechanisms. Special HPNS signs like vertigo and tremor suggested
      sensory-motor hyperexcitability resulting from brainstem dysfunction. We
      therefore studied brainstem auditory evoked potential (BAEP) repeatedly in four
      divers during an experimental deep helium-oxygen saturation dive to 450 meters of
      seawater (msw). Wave I (auditory nerve response) latency decreased whereas
      interpeak latencies (IPLs) I-III and I-V, which indicate respective cochleo
      pontine and cochleo-mesencephalic transmission time, prolonged during the dive.
      IPLs III-V also prolonged the dive, but with greater variability among divers.
      Two divers showed a marked reversal of the normal attenuation effect of increased
      stimulus presentation rates on IV and V amplitudes during compression, an effect
      that subsided during the stay at bottom depth. This finding might indicate a
      relative enhancement of synaptic excitability and is presumed to be a feature of
      HPNS. Wave I latency reduction might at least partly be caused by accelerated
      sound conduction in dense helium. Additionally, an upward shift of middle ear
      resonance frequencies in helium can induce a basal shift of the main cochlear
      portion responding to the wide band clicks. This effect may reduce wave I latency
      due to greater relative input from the basal high frequency-short latency
      cochlear neurons. Pressure-induced decrease of nerve conduction velocity, delay
      of synaptic transmission, and inhibitory modulation of midbrain auditory
      afferents possibly contributed to observed interpeak latency prolongations.
      Clinical HPNS signs, such as tiredness, dizziness, postural and intentional hand
      tremor, ataxia, and opsoclonus, were noted in three divers after reaching 300 msw
      and continued throughout the 37-h stay at bottom depth.

PMID- 7580765
TI  - Maximum sustained fin-kick thrust in underwater swimming.
AB  - We examined the upper limit of a diver's fin-kick thrust force using a stationary
      swimming ergometer. Heart rate, respiratory minute volume, oxygen uptake, and
      performance rate were measured in four male subjects who swam constantly for 8
      min to maintain a horizontal position against an applied force at a depth of 0.7
      m. The water temperature was controlled at 26 degrees +/- 1 degree C. The
      performance rate, which was the parameter of how well the subjects compensated
      for the applied load, showed an upper limit around 64 N of sustainable thrust
      force. This meant that the diver could generate the swimming thrust force within
      64 N continuously for 8 min in a steady state. Heart rate, respiratory minute
      volume, and O2 uptake showed almost proportional increases to the applied load
      within 64 N and tended to plateau about 69 N.

PMID- 7580766
TI  - Calibration of a bubble evolution model to observed bubble incidence in divers.
AB  - The method of maximum likelihood was used to calibrate a probabilistic bubble
      evolution model against data of bubbles detected in divers. These data were
      obtained from a diverse set of 2,064 chamber man-dives involving air and heliox
      with and without oxygen decompression. Bubbles were measured with Doppler
      ultrasound and graded according to the Kisman-Masurel code from which a single
      maximum bubble grade (BG) per diver was compared to the maximum bubble radius
      (Rmax) predicted by the model. This comparison was accomplished using multinomial
      statistics by relating BG to Rmax through a series of probability functions. The
      model predicted the formation of the bubble according to the critical radius
      concept and its evolution was predicted by assuming a linear rate of inert gas
      exchange across the bubble boundary. Gas exchange between the model compartment
      and blood was assumed to be perfusion-limited. The most successful calibration of
      the model was found using a trinomial grouping of BG according to no bubbles,
      low, and high bubble activity, and by assuming a single tissue compartment.
      Parameter estimations converge to a tissue volume of 0.00036 cm3, a surface
      tension of 5.0 dyne.cm-1, respective time constants of 27.9 and 9.3 min for
      nitrogen and helium, and respective Ostwald tissue solubilities of 0.0438 and
      0.0096. Although not part of the calibration algorithm, the predicted evolution
      of bubble size compares reasonably well with the temporal recordings of BGs.

PMID- 7580769
TI  - Incidence of bony outgrowths of the external ear canal in U.S. Navy divers.
AB  - Bony outgrowths of the temporal bone into the external ear canal are common in
      populations that participate in cold water activities. The incidence in
      professional divers is unknown. Eighty-seven U.S. Navy divers were interviewed
      and examined to determine the history of aquatic activity and degree of ear canal
      compromise. An age-matched control population of 42 non-divers without
      significant history of aquatic activities was also examined. The outgrowths, or
      exostoses, were found in 23 (26%) divers, and in no controls. Sixteen (70%) of
      the exostoses were minor, causing 10-20% narrowing of the auditory canal. The
      largest exostoses were found in divers with an extensive history of aquatic
      activities. The difference in total hours of aquatic activity was significant
      between divers and controls. The difference in total hours diving, as well as
      total time of all aquatic activities, was statistically significant between
      divers with exostoses and those divers without exostoses. The data confirm the
      relatively common incidence of this condition in a professional diving community.

PMID- 7580768
TI  - Diving at altitude: a review of decompression strategies.
AB  - Diving at altitude requires different tables from those at sea level due to the
      reduction in surface ambient pressure. Several algorithms extrapolating sea-level
      diving experimental data have been proposed to construct altitude diving tables.
      The rationale for these algorithms is reviewed together with the conservatism of
      the resulting tables and decompression computer outputs. All algorithms are based
      on the adaptation of critical tissue tensions to altitude. These are linear
      extrapolation (LEM), constant ratio translation (CRT), and constant ratio
      extrapolation (CRE) of maximum permissible tissue tensions (M values). Either new
      tables using the altitude-adapted M values were put forward or sea-level tables
      are to be used through an operation called correction. In this review it is shown
      that for a given set of M values, CRT and CRE give the same result for no
      decompression-stop dives; they always yield more conservative results than LEM.
      When decompression stops are used, CRT is more conservative than CRE. When
      applied to different sets of M values, the conservatism becomes a function of
      bottom time, depth, and altitude. The analysis shows that the tables derived
      using CRT of U.S. Navy (USN) schedules and CRE Boni et al. tables give more
      conservative results than LEM Buhlmann tables for higher altitude, longer bottom
      time, and deeper dives. Aviation altitude exposure decompression sickness (DCS)
      data are also addressed to compare different model outputs. When applied to USN
      and Royal Navy tables, LEM yields an altitude DCS limit of 8,581 and 8,977 m,
      respectively. On the other hand, the altitude limit calculated using CRE applied
      to USN M values and LEM Buhlmann tables is found to be below 6,000 m.

PMID- 7580767
TI  - Does the time course of bubble evolution explain decompression sickness risk?
AB  - A probabilistic model of decompression sickness (DCS) risk based on linear
      exponential (LE) kinetics has given the best fit of the human air and nitrox DCS
      database. To test the hypothesis that its success may be due to the formation of
      a gas phase during decompression, we developed a physiologically based bubble
      evolution model using a numerical solution of a partial differential equation
      system. Because of the computational intensity of this method, it could not be
      used to fully explore our hypothesis. Consequently, we compared the solution with
      that of a computationally simpler approximation that was previously published by
      Van Liew and found the two approaches gave similar results. Using the simpler
      model, assuming bubble densities of 1 and 1,000 bubbles/cm3, we found a tissue
      time constant of at least 80 min (equivalent to perfusion of 1/80 ml.g-1.min-1)
      was required to achieve a delay in bubble dissolution comparable to the prolonged
      risk of DCS predicted by the LE model. We suggest that the persistence of single
      bubbles in a uniformly perfused homogeneous tissue alone is unlikely to explain
      persistent DCS risk.

PMID- 7580770
TI  - Maine's urchin diver: a survey of diving experience, medical problems, and diving
      related symptoms.
AB  - A questionnaire was sent to 1,545 licensed, hand-harvesting Maine urchin divers
      to survey diving experience, habits, environment, medical problems, and symptoms;
      323 surveys were returned. Most of the respondents were young males who
      considered themselves physically fit; however, 17% were over 41 and 4% considered
      themselves "out of shape." Most had more than one occupation. Only 2% admitted no
      formal training, and breadth of experience fell into a trimodal distribution.
      Over half dove 2-5 times daily, most often under 60 ft. "Bounce" diving without
      decompression stops was usual, and solo diving was frequent. Eighteen percent had
      chronic medical problems, and 11% chronically used medications. The majority of
      diving was vigorous work from boats in the cold Maine ocean, not infrequently
      during poor weather. Seventy-eight percent described diving-related symptoms, and
      2% admitted to recompression therapy. Thus, these respondents depict themselves
      diving within marginal safety boundaries.

PMID- 7580771
TI  - Hyperbaric oxygen and high-frequency oscillator ventilation in experimental
      diaphragmatic hernia.

PMID- 7580773
TI  - Radiographic manifestations of eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis (EG) is a rare inflammatory disease of unknown
      etiology, characterized by focal or diffuse eosinophilic infiltration of the
      gastrointestinal tract. Although little over 250 cases of EG have been reported
      in the literature, EG is probably more common than reports in the literature
      would indicate. A retrospective review of 25 patients with EG along with a review
      of the literature was done to identify clinical, laboratory, radiographic, and
      therapeutic features. An allergic disorder was present in 14 (56%) and a
      peripheral eosinophilia was present in 24 (96%) of our patients. The most common
      radiographic manifestations of the stomach and small bowel included stenosis and
      fold thickening, respectively. Thirteen patients had esophageal involvement, with
      the esophageal stricture being the most common abnormality found in these
      patients. Steroids produced a good therapeutic result in most patients; the
      remaining patients responded to cromolyn and/or surgery.

PMID- 7580772
TI  - Diagnostic imaging evaluation of renovascular hypertension.
AB  - Over 50 million people in the United States are hypertensive. Renovascular
      disease accounts for 3-5% of these hypertensive patients. Because renovascular
      hypertension is potentially curable, much effort has been devoted to detecting
      and treating renal artery stenosis. Conventional angiography has been
      traditionally used to diagnose renal artery stenosis. However, because of its
      invasiveness and cost, conventional angiography cannot be utilized as a screening
      test in all patients who may have renal artery stenosis. Several noninvasive
      studies have been advocated for screening in hypertensive patients who may have
      renovascular disease. However, the accuracy of these noninvasive studies is
      widely variable, and appropriate use of these noninvasive studies needs to be
      better defined. Appropriate use of diagnostic imaging examinations for
      hypertensive patients depends on the index of suspicion for renovascular disease
      and on the patient's renal function. If certain clinical findings suggest the
      possibility of renovascular disease, then conventional angiography/intraarterial
      digital subtraction angiography should be performed. Captopril renography or
      duplex Doppler sonography could also be utilized if angiography is not desired or
      is contraindicated because of impaired renal function or a contrast allergy.
      Magnetic resonance angiography appears to be most helpful in a small, select
      group of patients who are likely to have proximal renal artery stenosis.

PMID- 7580775
TI  - Treitz redux: the ligament of Treitz revisited.
AB  - In the medical literature, the ligament of Treitz is frequently used as a term to
      designate the duodenojejunal flexure, but the attributes of the structure itself
      are not generally known. Indeed, anatomists describe it as the suspensory muscle
      of the duodenum, arising from the connective tissue around the stems of the
      celiac and superior mesenteric arteries and inserting as nonstriated muscle
      commonly into the third and fourth portions of the duodenum and frequently into
      the duodenojejunal flexure as well. Misconceptions regarding its configuration
      and anatomic relationships continue to be widely illustrated. The fibromuscular
      structure plays an important role in the embryologic rotation of the bowel and in
      facilitating normal progression of contents from the extraperitoneal duodenum to
      the mesenteric small bowel and contributes to the effects of the superior
      mesenteric artery syndrome. Whereas virtually all other ligaments and mesenteries
      in the abdomen have been imaged, features of the ligament of Treitz render its
      visualization by CT or MRI challenging.

PMID- 7580774
TI  - Imaging diagnosis of sclerosing peritonitis and relation of radiologic signs to
      the extent of the disease.
AB  - BACKGROUND: Sclerosing peritonitis (SP) is a serious complication of chronic
      ambulatory peritoneal dialysis (CAPD) that is characterized by thickened
      peritoneal membranes, leading to impaired ultrafiltration and intestinal
      obstruction. The aim of this study was to analyze the radiographic signs of SP in
      symptomatic patients and to compare them with the histological severity of the
      disease. METHODS: In 14 patients with symptoms of intestinal obstruction related
      to SP, plain films of the abdomen, upper GI follow-through examinations,
      ultrasonography, and computed tomography were evaluated retrospectively. Imaging
      findings such as bowel motility, bowel wall and peritoneal thickness, and the
      presence of intraperitoneal fluid collections were correlated to the histological
      degree of the fibrosis. RESULTS: Signs of intestinal obstruction and disturbed
      motility were present in all cases. In addition, patients with histologically
      severe SP had loculated fluid collections, thickening of the bowel wall and/or
      peritoneum, peritoneal calcifications, and thickened peritoneal membranes, and
      suffered more often from postoperative complications. CONCLUSION: The detection
      of characteristic radiographic signs in CAPD patients presenting with symptoms of
      intestinal obstruction may suggest the presence of severe SP and should lead to
      cautious surgical interventions.

PMID- 7580776
TI  - CT of the duodenojejunal junction.
AB  - To determine the location of the duodenojejunal junction (DJJ) at computed
      tomography (CT), we retrospectively reviewed 309 consecutive CT examinations.
      These included 162 men and 127 women (mean age = 57 years old, range = 11-85
      years old). Some people received more than one examination. The clinical
      indications included various kinds of neoplasms, inflammations, congenital
      lesions, trauma, and other conditions. The DJJ was defined as the first sectioned
      ascending duodenum whose major part lies to the right side of the crossing part
      of the inferior mesenteric vein over the immediate beginning of the jejunum.
      Forty-nine examinations were excluded due to distortion of the DJJ by contiguous
      pathologic processes or nonadministration of intravenous contrast medium. In 36
      examinations, the junctions were not identified. In the successfully identified
      224 examinations, the DJJ was located to the left in 75 (33.5%), in the left half
      in 87 (38.8%), and in the right half or to the right of the vertebral body in 4
      (1.8%) examinations. The midline of the DJJ was along the left margin and in the
      midline of the vertebral body in 53 (23.7%) and 5 (2.2%) examinations. In the
      anteroposterior direction, it was totally in front of the aorta in 189 (84.4%)
      and within the projected contour of the aorta in 11 (4.9%) examinations. The
      midline of the DJJ was along the anterior margin of the aorta in 24 (10.7%)
      examinations. Its cephalocaudal position was at the upper L1 in 36 (16.1%), lower
      L1 in 70 (31.3%), upper L2 in 75 (33.5%), and lower L2 in 21 (9.4%) examinations
      even though it ranged from upper T12 to upper L3.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7580777
TI  - Small bowel volvulus.
AB  - Two cases of small bowel volvulus with mild clinical symptoms in which upper
      gastrointestinal series, computed tomography, and magnetic resonance imaging were
      performed are reported. Angiography was also performed in one case. Neither
      patient received laparotomy and the diagnosis was based on imaging findings.

PMID- 7580778
TI  - The role of carbon dioxide and atmospheric air in double-contrast barium enema.
AB  - BACKGROUND: Patient discomfort 0-24 h after double-contrast barium enema (DCBE)
      was investigated in two ways. METHODS: In part 1, 139 patients, not previously
      informed, were contacted by telephone to assess symptom rates without bias. In
      part 2, designed as a prospective randomized double-blind trial, the effect of
      carbon dioxide (CO2) as an insufflating gas was compared with conventional
      atmospheric air (AA). RESULTS: Part 1: 10% experienced severe abdominal pain, and
      18% severe abdominal distention. Part 2: Low discomfort rates were found for both
      severe pain (7% for AA vs. 2% for CO2) and severe distention (13% for AA vs. 8%
      for CO2); the differences were not significant. In both parts of the study,
      female patients with a history of abdominal discomfort of "colon irritable" type
      were significantly overrepresented in the severely symptomatic groups. Equal
      numbers of patients experiencing severe abdominal distention for the first time
      were found in both the AA and CO2 groups, ruling out AA as the sole cause of
      these symptoms. CONCLUSION: Abdominal post-DCBE discomfort seems to be less
      frequent than previously reported and is not effectively eliminated by CO2. We
      still find the use of AA in DCBEs justified.

PMID- 7580779
TI  - Dilemma of an inverted cecal diverticulum simulating a pedunculated polyp: CT
      appearance.
AB  - The computed tomographic (CT) appearance of an intussuscepting cecal diverticulum
      is described. Some features on CT suggest that the term "inverted" may not be
      accurate.

PMID- 7580780
TI  - Evacuation proctography combined with positive contrast peritoneography to
      demonstrate pelvic floor hernias.
AB  - BACKGROUND: To demonstrate the pelvic peritoneal recesses during voiding,
      evacuation proctography was combined with positive contrast peritoneography.
      METHODS: In 30 constipated patients, peritoneography was performed, followed by
      proctography. RESULTS: During evacuation rectogenital herniation developed in 20
      patients (66%), without visceral filling in 12 (40%). CONCLUSIONS: Posterior
      pelvic floor hernia is common during defecation. Less than half fill with bowel
      and many may not be apparent on standard proctography.

PMID- 7580781
TI  - Lumbar herniation of the spleen.
AB  - Hernias of the lumbar region are rare but have been reported to occur after
      trauma, flank surgery, iliac bone grafting, spontaneously, or as a result of
      congenital abnormality of musculoskeletal development. The acquired type is more
      common than the congenital type. The contents of the hernia most commonly are
      retroperitoneal fat, kidney, and bowel. We report a case of an asymptomatic
      postincisional lumbar herniation of a spleen that was diagnosed by computed
      tomography.

PMID- 7580782
TI  - Imaging features of splenic epidermoid cyst with pathologic correlation.
AB  - The spleen can be involved in a variety of cystic lesions ranging from cystic
      neoplasms and parasitic cysts to "true" and "false" cysts. Epidermoid splenic
      cyst is a rare true cyst that is developmental in origin. We present two young
      patients with such a cyst and illustrate their features on ultrasound, CT, and
      MRI with pathologic correlation.

PMID- 7580783
TI  - Intrahepatic abscess due to gallbladder perforation.
AB  - BACKGROUND: Perforation of the gallbladder with cholecystohepatic communication
      is a rare cause of liver abscess. We report four cases of this condition and
      describe the imaging procedures related to its diagnosis and treatment. METHODS:
      The medical and x-ray files of 39 patients with percutaneous drainage of liver
      abscesses were retrospectively reviewed. Four patients with hepatic abscess due
      to gallbladder perforation were identified. The patients presented with clinical
      features suggestive of cholecystitis. RESULTS: Sonography in four patients showed
      a hypoechoic lesion in the liver adjacent to the gallbladder. CT in three
      patients showed a hypodense area in the liver, corresponding to the sonographic
      findings. Percutaneous abscess drainage, followed by an abscessogram, was
      performed in all patients. Contrast material injected through the drainage
      catheter filled the gallbladder directly from the abscess cavity. Two patients
      subsequently underwent cholecystectomy, confirming perforation of the gallbladder
      fundus. In both cases the gallbladder was noted to be embedded in the liver and
      covered by adhesions. CONCLUSION: Perforation of the gallbladder is a rare cause
      of pyogenic liver abscess. We suggest, however, based on our two patients who
      underwent surgery, and several cases reported in the literature, that this
      condition may be more common when the gallbladder is partially or totally
      intrahepatic.

PMID- 7580784
TI  - Right hepatic lobe agenesis associated with bile duct carcinoma.
AB  - A patient with obstructive jaundice was found to have bile duct carcinoma and
      right hepatic lobe agenesis. The diagnosis was made by computed tomography (CT),
      cholangiography, and angiography. Right hepatic lobe agenesis is a rare anomaly
      and has never been previously reported with bile duct carcinoma. CT
      cholangiography was critical in diagnosing the morphologic anomalies of the bile
      duct in this case.

PMID- 7580785
TI  - Nonenhanced hepatic cavernous hemangioma with multiple calcifications: CT and
      pathologic correlation.

PMID- 7580786
TI  - Spontaneous dissection of the hepatic artery.
AB  - Two cases of spontaneous dissection of hepatic arteries are described.
      Presentation and management of these two patients are distinctly different. The
      first patient presented with mild back pain and mild abnormal liver function
      tests and was treated conservatively. The second patient presented with
      hemoperitoneum and shock and was treated surgically.

PMID- 7580787
TI  - Spontaneous aortocaval fistula: CT findings with pathologic correlation.
AB  - We present a case of aortocaval fistula (ACF) secondary to spontaneous rupture of
      an atherosclerotic infrarenal aortic aneurysm into the inferior vena cava that
      was initially diagnosed with computed tomography (CT). This is believed to be the
      first report of this condition with CT demonstration of the exact site of fistula
      and CT-pathologic correlation. We retrospectively reviewed the CT findings of
      another two cases of ACF and the previous literature.

PMID- 7580789
TI  - Thrombophlebitic retroperitoneal collateral veins mimicking lymphadenopathy: MR
      and CT appearance.
AB  - The authors report the magnetic resonance (MR) and computed tomography (CT)
      features of what is believed to be thrombophlebitis of the left cava of a
      duplicated IVC, which mimicked lymphadenopathy, and prompted both a CT-guided
      needle aspiration biopsy and surgical exploration. Knowledge that retroperitoneal
      vascular anomalies can mimick lymphadenopathy, both clinically and
      radiographically, may help obviate further testing and intervention.

PMID- 7580790
TI  - Calcifications of portal venous system wall: CT findings in three patients.
AB  - Three cases of portal venous system wall calcifications demonstrated by computed
      tomography are presented. The clinical features, possible pathogenesis,
      differential diagnosis, and therapeutic significance of this condition are
      reviewed.

PMID- 7580788
TI  - Aneurysms of the pancreaticoduodenal artery associated with occlusion of the
      celiac artery.
AB  - Aneurysms of the pancreaticoduodenal artery are rare and may be associated with
      celiac artery stenosis or occlusion. Twenty-eight patients are reported in the
      literature. The diagnostic findings and therapeutic alternatives of four
      additional patients form the basis of this report. One patient with ruptured
      pancreaticoduodenal aneurysm was successfully treated by transcatheter
      embolization, and one patient was treated surgically; both patients had an
      uneventful recovery. In the remaining two patients, the aneurysms were left
      untreated. One patient died 1 year later of an unrelated cause, and the other
      patient is symptom-free after 2 years.

PMID- 7580791
TI  - Verrucous carcinoma of the bladder.
AB  - Verrucous carcinoma is a rare squamous cell variant that may arise in the
      bladder. We present a case of verrucous carcinoma of the bladder with radiologic
      pathologic correlations that demonstrate the characteristic frond-like growth
      pattern. Verrucous carcinoma is an invasive but not a metastizing lesion, and
      therefore recognizing this lesion may have prognostic and therapeutic
      implications.

PMID- 7580793
TI  - Gravid uterine dehiscence: MR findings.
AB  - Gravid uterine rupture can be a difficult diagnosis, both clinically and
      radiologically. Ultrasound has been successful in detection of some indirect
      signs of uterine rupture but thus far has shown little success in demonstrating
      the myometrial defect. We present the MR findings in a case of gravid uterine
      dehiscence in which the actual uterine wall defect was well demonstrated. Gross
      pathologic correlation is provided.

PMID- 7580792
TI  - CT demonstration of liquid intratumoral fat layering in a necrotic renal cell
      carcinoma.
AB  - We describe a case of clear-cell adenocarcinoma of the kidney with CT evidence of
      fat that contradicts the rule that radiologically demonstrable fat is absent in
      renal carcinoma. The cyst-like appearance, egg-shell parietal calcifications, and
      extrarenal development of the mass suggested a preoperatively incorrect diagnosis
      of teratoma.

PMID- 7580794
TI  - Adrenocortical adenoma containing a fat component: CT and MR image evaluation.
AB  - A case of adrenocortical adenoma containing small adipose foci is presented. A
      small amount of fat within the mass led to an erroneous preoperative diagnosis of
      myelolipoma. Adrenal adenoma should be included in the differential diagnosis of
      adrenal mass containing fat.

PMID- 7580795
TI  - Disorders in fixation of the cecum and ascending colon.

PMID- 7580796
TI  - Diagnosis of minimal to moderate pneumoperitoneum.

PMID- 7580797
TI  - 16S-23S and 23S-5S intergenic spacer regions of Streptococcus thermophilus and
      Streptococcus salivarius, primary and secondary structure.
AB  - The 16S-23S intergenic spacer region (spacer region 1) of Streptococcus
      salivarius, S. thermophilus, and Lactococcus lactis subsp. cremoris and the 23S
      5S intergenic spacer region (spacer region 2) of S. salivarius and L. lactis
      subsp. cremoris were sequenced and compared with the spacer regions 1 and 2 of
      other streptococci. A high degree of intraspecific conservation was observed for
      S. thermophilus and L. lactis, and very similar sequences were found for S.
      salivarius and S. thermophilus. Whereas spacer region 1 is highly conserved in
      the genus Streptococcus sensu-stricto, only the tRNA gene and the rRNA processing
      stems are highly conserved in the three genera: Streptococcus sensu-stricto,
      Lactococcus, and Enterococcus. The presence of a unique tRNA(Ala) gene without
      the 3' terminal CCA sequence seems to be a general feature of the streptococci
      spacer region 1. A secondary structure model was built to show the interaction
      between the spacer regions 1 and 2 of S. thermophilus and S. salivarius. The
      rapid evolution of spacer region 1 in streptococci is in part due to insertions
      and deletions of small RNA stem/loop structures.

PMID- 7580799
TI  - Isolation of Ewingella americana from mollusks.
AB  - Twenty-three of 2446 strains of Enterobacteriaceae isolated from mollusks were
      identified as Ewingella americana both biochemically and by DNA hybridization
      with strain S6/1111. The biochemical characteristics of the new strains showed
      few differences from previously reported strains obtained from human clinical
      specimens. These are the first strains of E. americana isolated from animals.

PMID- 7580798
TI  - Use of synthetic peptides to identify surface-exposed, linear B-cell epitopes
      within outer membrane protein F of Pseudomonas aeruginosa.
AB  - In a previous study (Hughes EE, Gilleland LB, Gilleland HE Jr. [1992] Infect
      Immun 60:3497-3503), ten synthetic peptides were used to test for surface-exposed
      antigenic regions located throughout the length of outer membrane protein F of
      Pseudomonas aeruginosa. An additional nine peptides of 11-21 amino acid residues
      in length were synthesized. Antisera collected from mice immunized with each of
      the 19 synthetic peptides conjugated to keyhole limpet hemocyanin were used to
      determine which of the peptides had elicited antibodies capable of reacting with
      the surface of whole cells of the various heterologous Fisher-Devlin immunotypes
      of P. aeruginosa. Cell surface reactivity was measured by an enzyme-linked
      immunosorbent assay (ELISA) with whole cells of the various immunotypes as the
      ELISA antigens and by opsonophagocytic uptake assays with the various peptide
      directed antisera, immunotype 2 P. aeruginosa cells, and polymorphonuclear
      leukocytes of human and murine origin. Three peptides located in the carboxy
      terminal portion of protein F elicited antibodies with the greatest cell-surface
      reactivity. Peptide 9 (TDAYNQKLSERRAN), peptide 10 (NATAEGRAINRRVE), and peptide
      18 (NEYGVEGGRVNAVG) appear to have sufficient potential for further development
      as vaccine candidates for immunoprophylaxis against infections caused by P.
      aeruginosa. A topological model for the arrangement of protein F within the outer
      membrane of P. aeruginosa is presented.

PMID- 7580800
TI  - Differentiation of ruminal and human Streptococcus bovis strains by DNA homology
      and 16s rRNA probes.
AB  - Streptococcus bovis is commonly present in the rumen, but strains of S. bovis
      have also occasionally been isolated from human blood or fecal samples. Studies
      were undertaken with 16s rRNA gene sequences and DNA hybridizations to define the
      genetic relationships between these two groups of strains. Ruminal strains were
      found to yield genomic DNA restriction endonuclease digest patterns different
      from human strains when either the 16s rRNA gene amplified from ruminal S. bovis
      strain JB1 or a conserved universal 23s rRNA fragment was used as probes. A DNA
      probe based on the V1 region of the 16s rRNA of S. bovis JB1 was found to
      hybridize to DNAs of other ruminal S. bovis strains (K27FF4, 21-09-6C, five new
      ruminal isolates, and weak hybridization was found with DNAs from S. bovis 33317
      (type strain), S. equinus 9812, and six other ruminal isolates. No hybridization
      occurred with strains representing different major human biotypes/homology groups
      (43143, 43144, 27960, V1387). All ruminal S. bovis strains had a guanosine plus
      cytosine DNA content of 37.4-38.8 mol% and, based on DNA-DNA genomic
      hybridizations, could be separated into two homology groups, one of which
      included S. equinus 9812 and S. bovis 33317. Both ruminal groups had less than
      38% DNA homology to the human strains, indicating ruminal strains are clearly two
      separate species distinct from the human strains.

PMID- 7580801
TI  - Glycerol effect on spiramycin production and valine catabolism in Streptomyces
      ambofaciens.
AB  - Spiramycin production by Streptomyces ambofaciens in a chemically defined medium,
      with valine as nitrogen source, was controlled by the nature and the
      concentration of the carbon source. The production of this antibiotic was better
      in dextrins than in glycerol-containing medium. The negative effect of glycerol
      could be attributed in part to an excess of energy and a high specific growth
      rate. The intracellular ATP content, at the start of spiramycin production, was
      twofold higher in glycerol than in dextrin-containing medium. Increasing the
      initial concentrations of glycerol led to an increase in the specific growth rate
      and a drop in spiramycin production. Comparison between glycerol and a protein
      synthesis inhibitor effects and the use of resting cell systems (RCS) proved that
      glycerol exerted both inhibitory and repressive actions on spiramycin production
      independently from the growth. At the enzymatic level, glycerol interfered with
      valine catabolism by repressing partially valine dehydrogenase (VDH) and alpha
      ketoisovalerate dehydrogenase (KIVDH), generator of spiramycin aglycone
      precursors.

PMID- 7580804
TI  - Molecular aspects of cyclic GMP signaling.

PMID- 7580803
TI  - Natriuretic peptides and their receptors.

PMID- 7580802
TI  - Extracellular neuraminidase production by Pasteurella species isolated from
      infected animals.
AB  - A total of 721 field isolates of various Pasteurella species (haemolytica,
      multocida, and testudinis) from various regions of the United States were
      examined for extracellular neuraminidase production. All strains were grown and
      tested in the same way. Included were 372 P. haemolytica serotype 1 isolates, 181
      P. haemolytica serotype 2 isolates, 63 P. haemolytica serotype 6 isolates, 101
      Pasteurella multocida isolates, and 4 Pasteurella testudinis isolates. All
      Pasteurella species examined produced the enzyme. The data revealed the
      following: (1) Several transfers of P. haemolytica strains on blood agar medium
      did not cause a decrease in enzyme activity. (2) P. haemolytica serotypes 2 and 6
      produce more neuraminidase than P. haemolytica serotype 1, P. multocida, and P.
      testudinis isolates. (3) There was no apparent change in neuraminidase production
      by P. haemolytica serotypes 1 and 2 obtained from the same animal taken on
      different days in the feedyard. (4) There was no significant change in
      neuraminidase production by P. haemolytica serotype 2 isolates taken from the
      same animal at the auction market and later at the feedyard.

PMID- 7580805
TI  - Electrical properties of the cerebral prothoracicotropic hormone cells in
      diapausing and non-diapausing pupae of the tobacco hornworm, Manduca sexta.
AB  - Prothoracicotropic hormone (PTTH) is an insect brain neuropeptide that is a
      primary factor regulating an insect development. Curtailment of its release is
      thought to be responsible for the pupal diapause of tobacco hornworm, Manduca
      sexta. The cell synthesizing and secreting the PTTH has been identified as a pair
      of neurosecretory cells in the pars lateralis on each brain hemisphere. Using
      intracellular recording techniques, we have demonstrated electrical properties of
      the PTTH cells in different physiological status, i.e., diapausing and developing
      pupae. In diapausing pupae, they showed threshold value increasing and input
      resistance decreasing with the progress of diapausing state, indicating that they
      were getting unexcitable. Spontaneous action potentials and excitatory
      postsynaptic potentials (EPSPs) were rarely observed in deeply diapausing state.
      Non-diapausing PTTH cells were almost silent except day-2, showing rather
      constant values of electrical properties. On day-2, a significant proportion of
      the cells had spontaneous action potentials, showing less negative membrane
      potential values than inactive cells. Exclusively inhibitory postsynaptic
      potentials (IPSPs) were observed in significant numbers of the cells during the
      period from day-2 to day-5. On the basis of the results obtained, we proposed a
      working hypothesis that electrical activities of the PTTH cell may be primarily
      regulated by its membrane properties which are further modulated by the synaptic
      mediation.

PMID- 7580806
TI  - Angiotensin II suppresses water absorption through the ventral skin of Japanese
      tree-frogs in vitro.
AB  - We previously described two different water absorption systems in the ventral
      skin of the Japanese tree-frog, Hyla arborea japonica: i.e., a rapid enhanced
      flow, which is observed in dehydrated tree-frogs or those stimulated by
      adrenaline beta-agonists or vasotocin, and a slow basal flow, which is observed
      in normally hydrated frogs during the non-breeding season. The rapid flow is
      completely blocked by ouabain, which has no effects on the slow basal flow. In
      the present experiment, we show that the vaso-constrictive hormone angiotensin II
      completely inhibits basal water absorption, but has no effect on rapid water
      absorption. These results confirm our previous finding that the two water
      absorption systems in the ventral skin of the Japanese tree-frog are independent
      of each other.

PMID- 7580807
TI  - Humoral defense of the nematode Ascaris suum: antibacterial, bacteriolytic and
      agglutinating activities in the body fluid.
AB  - Three humoral defense activities (antibacterial, bacteriolytic and agglutinating)
      were detected in the body fluid of the nematode Ascaris suum. Gram-positive
      bacteria (Staphylococcus aureus and Bacillus subtilis) were more sensitive to the
      antibacterial activity than the Gram-negative bacteria (Escherichia coli). The
      antibacterial activity was heat stable and was lost by trypsin digestion. The
      molecular mass of the factor responsible for antibacterial activity was estimated
      as 6 kDa. The bacteriolytic activity against dried Micrococcus luteus was also
      detected. The bacteriolytic factor was 6-9 kDa in molecular mass, heat sensitive
      and trypsin sensitive. Both E. coli and glutaraldehyde-fixed trypsin-treated
      human A-type red blood cells were agglutinated in the body fluid. An analytical
      gel permeation HPLC revealed the agglutinating activity consists of at least two
      factors. Activities of both agglutinating factors were lost by heat treatment or
      trypsin digestion. The molecular masses estimated for the two agglutinating
      factors were 500 kDa and 25 kDa. Under experimental conditions, microbe-injection
      was not a prerequisite for the appearance of these defense activities.

PMID- 7580808
TI  - Developmental pattern of androgen receptor immunoreactivity in the mouse
      submandibular gland.
AB  - We studied the immunohistochemical localization of androgen receptor in the mouse
      submandibular gland, and developmental profiles of its expression using
      polyclonal human androgen receptor antibody. In the submandibular glands of both
      sexes, specific immunoreactivity appeared only in cell nuclei of the acini, the
      intercalated ducts, the granular convoluted tubules (GCT) and the excretory
      striated ducts. The percentage of immunoreactive cells in each region gradually
      declined with age during the first 90 days of postnatal development studied. The
      sexual difference in the percentage of immunoreactive cells was observed in the
      acini on days 20 and 30 and in the GCT on day 30. Incidence of immunoreactive
      cells in the female was significantly smaller than that in the male. On day 60,
      the percentage of immunoreactive cells of these two regions turned to increase
      slightly in the female but continued to decline in the male, and then it became
      higher in the female than in the male. In addition, one-week castration did not
      cause any changes in the intracellular distribution of androgen receptor and the
      percentage of immunoreactive cells in each region of the adult gland. These
      results suggest that androgen receptor is localized primarily in cell nuclei in
      all four regions of the mouse submandibular gland in situ, and that its
      expression in acini and GCT is superior in the male around days 20 to 30, when
      sex difference of the gland becomes evident.

PMID- 7580809
TI  - Neuroendocrine communication in the frog adrenal gland.

PMID- 7580810
TI  - Effects of Mg2+ on the stimulation-induced changes in transmitter release at the
      frog neuromuscular junction.
AB  - Four components of stimulation-induced changes in neurotransmitter release are
      known as the synaptic plasticity at the frog neuromuscular junction. These are:
      fast and slow facilitation, augmentation and potentiation, classified by their
      decay time constants after repetitive nerve stimulation. Most experiments support
      the view that fast facilitation is caused by residual Ca2+. However, the causes
      of the other three components are not clear. We have studied
      electrophysiologically the effect of Mg2+ on these three components. Transmitter
      release was estimated by the amplitudes of endplate potential (EPP) and by the
      frequencies of miniature endplate potential (MEPP). The increase in the
      transmitter release by nerve stimulation is described as the product of four
      components. The magnitude of potentiation of MEPP frequencies after a tetanic
      nerve stimulation (100 Hz, 5000 times) increased markedly in high Mg2+
      concentrations. Conversely, the magnitude of augmentation (MEPP frequencies and
      EPP amplitude) decreased in the higher Mg2+ Ringer solution.

PMID- 7580811
TI  - Effect of adrenocorticotropic hormone (ACTH) and insulin on the phagocytic
      capacity of Tetrahymena.
AB  - Adrenocorticotropic hormone (ACTH) and insulin negatively influenced the
      phagocytic activity of Tetrahymena. The two hormones had diverse effects after 4
      hr of treatments on no-test-particle containing, "0-cells". At this time the
      number of "0 cells" was significantly lower in the ACTH-treated groups, while in
      the insulin-treated groups there was an increase of "0-cells" compared to the
      control and to the results of the starting experiment. Considering previous
      results, when small molecular weight hormones, if did at all, positively
      influenced phagocytosis in Tetrahymena, the experiments call the attention to the
      differences caused by the size of the signal molecules. In the light of the
      literary data on hormone effects to phagocytosis in mammals and men, the
      similarity of the effects in species being very far from each other in evolution,
      could be concluded.

PMID- 7580812
TI  - The difference in autofluorescence features of lipofuscin between brain and
      adrenal.
AB  - Lipofuscin is the autofluorescent material, which accumulates with aging in the
      cells of various tissues. However, its autofluorescence characteristics are
      different among tissues. In the present study, the autofluorescence features of
      lipofuscin in the brain and adrenal were compared. In 18-21-month-old rats, the
      brain lipofuscin was granular and its autofluorescence was bright whitish-yellow
      to bright orange. On the contrary, the adrenal lipofuscin was not demarkated as
      granules, and its autofluorescence was subdued orange. The emission maximum of
      the bright whitish-yellow brain lipofuscin was 540 nm to 570 nm and that of the
      adrenal lipofuscin was 640 nm to 660 nm, when excited at 330 nm to 380 nm. When
      the spectra were drawn after correcting the wavelength-dependent bias of
      microspectrofluorometer, the autofluorescence spectra were consistent with
      microscopically observable tint. To conclude, the present results showed that the
      autofluorescence features of the bright whitish-yellow brain lipofuscin and the
      adrenal lipofuscin were quite different.

PMID- 7580814
TI  - The traffic of particles in the axonic process of vertebrate cone-type
      photoreceptor cells.
AB  - Differential-interference-contrast microscopy with video enhancement displayed
      the movement of particles for the first time in the isolated axonic process of
      cone-type photoreceptor cells of Rana catesbiana. This movement was observed
      under visible light which visual pigments could absorb. The number of retrograde
      moving particles in an arbitrary area on the axonic process was twice that of
      those moving in the anterograde direction. The mean velocities were 1.03 +/- 0.55
      microns/sec for anterograde particles and 0.41 +/- 0.30 microns/sec for
      retrograde particles, which are of the same order as those found in isolated
      neurons.

PMID- 7580813
TI  - Regeneration of axons in transection of the carp spinal cord.
AB  - Axonal regeneration in the central nervous system (CNS) was investigated in the
      fine structural and histochemical aspects using carp spinal cord, which was
      completely transected at the level of the dorsal fin. Fusion of the transection
      region and the regeneration of axons already began to be recognized 26 days after
      operation by electron microscopy. At 115 days after operation, the rostral and
      caudal parts of the transected spinal cord were completely connected by the
      regenerating nervous tissue, which contained numerous axons among the ependymal
      and glial processes. Horseradish peroxidase (HRP), which was injected in the
      spinal cord at the portion caudal to the transection site was detected in the
      cytoplasm of large neurons located in the reticular formation of midbrain. This
      demonstrates that these long axons were regenerated passing through the ablation
      gap 151-204 days after operation. These findings indicate that regenerating axons
      in the carp spinal cord can pass through the glial scar formed in the transected
      portion, which is considered to be the main obstacle for the prolongation of
      axons in the mammalian CNS. Many regenerating axons, both unmyelinated and
      myelinated, were observed being in contact directly with the cell membrane of the
      ependymal as well as astroglial cells. This indicates that neither ependymal nor
      glial cells play a role as an obstacle for elongation of axons in the carp spinal
      cord. Numerous GFAP (glial fibrillary acidic protein) positive intermediate
      filaments were observed in the cell bodies and cytoplasmic processes of both
      ependymal cells and astroglia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580816
TI  - Acamprosate in alcohol dependence: how does it work?
AB  - Acamprosate is a relatively new drug that appears to be clinically useful in the
      treatment of alcohol dependence. Although it has proved effective in reducing
      relapse into drinking in clinical trials its exact mechanism of action is
      uncertain. Evidence is presented that the drug does not act in any of the
      conventional ways to reduce alcohol intake and it is proposed that it may be a
      novel kind of agent that suppresses "craving". On the basis of its known
      pharmacological effects in pre-clinical studies it is suggested that acamprosate
      may reduce craving that is associated with conditioned withdrawal. In addition to
      the potential therapeutic value of acamprosate, the drug may be useful because
      work directed toward understanding its mechanism of action may shed light on some
      of the fundamental processes that govern alcohol abuse and relapse in weaned
      alcohol dependent patients.

PMID- 7580815
TI  - Controlled drinking after 25 years: how important was the great debate?

PMID- 7580817
TI  - An evaluation of type A and B alcoholics.
AB  - Evaluations of 1539 alcohol-dependent subjects (including 512 women) were carried
      out in an attempt to replicate the Type A/B dichotomy suggested by Babor et al.
      (1992). The subjects are participants in the Collaborative Study on the Genetics
      of Alcoholism (COGA), and each was evaluated using a face-to-face structured
      interview. Following the procedure of Babor et al. (1992), data were used to
      create 17 domains, and a k-means clustering method was invoked to generate a two
      cluster solution. Thirty-one per cent of the males and 25% of the females fell
      into the Type B group, with overall R2 of 0.22 and 0.24 for males and females,
      respectively. The scores in each of the 17 domains and the analyses of the
      clinical characteristics for Type A and B subjects were, in general, consistent
      with the earlier onset and more severe course for Type B men and women. The
      ability of the domains to identify subgroups of alcoholics remained robust even
      after the exclusion of alcohol dependent subjects with antisocial personality
      disorder (ASPD) and those with an onset of alcohol dependence before age 25
      years. The present analyses suggest that five of the 17 domains might be
      especially useful in identifying Type A and B groups.

PMID- 7580818
TI  - Family history of alcoholism and psychiatric co-morbidity in Brazilian male
      alcoholics and controls.
AB  - The present study was aimed at replicating, in a sample of Brazilian subjects,
      findings generated mostly in developed countries on the relative prevalence of
      alcohol problems, associated psychiatric disorders, family history of alcoholism
      and other familial psychiatric disorders in alcoholics and controls. A group of
      Brazilian male alcoholics (n = 103) and controls (n = 63) at first admission to
      ambulatory or inpatient treatment were interviewed individually using sections of
      the Structured Clinical Interview for DSM-III-R. Information on demographic
      characteristics, alcohol-related problems, psychiatric problems and family
      history of alcoholism and depression were collected from all subjects. Alcoholics
      had a higher prevalence of a family history of alcoholism, a family history of
      depression and of a personal history of other psychiatric disorders when compared
      to controls. Comparisons between FHP and FHN alcoholics, although preliminary,
      showed few significant differences between these subgroups. Comparisons between
      FHP and FHN control showed a non-significant trend towards a higher prevalence of
      psychiatric problems and towards antisocial behaviours among those with a
      positive family history of alcoholism. The findings point to the importance of
      cross-cultural studies on genetic and environmental factors related to alcohol
      dependence.

PMID- 7580820
TI  - Entering treatment for alcohol abuse: a stress and coping model.
AB  - This study used a stress and coping model to examine the process of entering
      treatment among 515 problem drinkers without prior formal treatment for alcohol
      abuse who were recruited at alcoholism information/referral (I&R) and
      detoxification centers. Over a 1-year follow-up period, 76% of the individuals in
      the sample entered some form of treatment, including Alcoholics Anonymous. People
      were more likely to enter treatment if they perceived their drinking problem as
      more severe, had more dependence symptoms, experienced more adverse consequences
      as a result of drinking, had more symptoms of depression, were more self
      derogating, experienced more negative life events in the past year, and/or
      experienced more stressors in various life domains. Facilitative factors also
      related positively to treatment entry: people who had sought help from non-formal
      treatment sources before, who recalled being referred to treatment programs by an
      I&R center, and/or who received detoxification at a center that had treatment
      services available on-site, also were more likely to enter treatment. For people
      with greater resources in multiple life domains the positive effects of days
      intoxicated, dependence symptoms and stressors on help-seeking were intensified.
      Overall, the findings suggest that perceived severity of drinking problem plays a
      central role in the treatment entry process and mediates the effects of many
      other intrapersonal and environmental variables in generating an impetus or
      readiness to seek treatment.

PMID- 7580821
TI  - Situations occasioning cocaine use and cocaine abstinence strategies.
AB  - We interviewed 265 cocaine-experienced methadone patients about situations that
      occasioned their cocaine use and strategies they used to avoid cocaine use.
      Subjects identified an average of 15 situations that occasioned cocaine use. The
      three most frequently identified were having the drug present (86% of subjects),
      being offered the drug (85%) and having money available (83%). Subjects reporting
      fewer situations also reported longer periods of lifetime abstinence (p < 0.01).
      A principal components analysis extracted 10 groups of situations that were most
      frequently identified in combination. Subjects identified a median of seven
      strategies for avoiding cocaine use; however, there was large inter-subject
      variability. This variance was not accounted for by demographic variables,
      employment status or treatment experience. The three strategies identified most
      frequently were avoiding people and places (81%), thinking about what they could
      lose (76%) and leaving the situation (66%). The total number and type (reactive
      vs. proactive) of strategies identified by subjects had no relationship to
      cocaine abstinence, although four specific strategies (thinking about what could
      be lost, leaving the situation, moving to a new area and using a different drug)
      were positively correlated with cocaine abstinence. We discuss implications of
      these results for clinical practice.

PMID- 7580819
TI  - Alcohol and drug problems: a multivariate behavioural genetic analysis of co
      morbidity.
AB  - Multivariate biometrical genetic analyses of self-report questionnaire items
      assessing problem alcohol and drug use were performed on data obtained from a
      sample of 438 volunteer twin pairs (236 monozygotic twin pairs, 247 dizygotic
      twin pairs). Additive genetic influences were moderate for all alcohol abuse
      items (21-46%), frequency of drug use (32%) and illicit drug use (32%).
      Prescribed drug use and debilitating drug use were largely environmentally
      determined (86% and 94%, respectively). The influence of environmental factors
      that influence all members of a family to the same degree (shared family
      environment) on each item was generally small (0-20%), whereas the influence of
      environmental factors unique to each family member (non-shared environment)
      comprised over half of the total variance on all items. Genetic factor analyses
      identified three uncorrelated common genetic factors. The first genetic factor
      appears to represent problems associated with alcohol and drug use, such as the
      inability to fulfil obligations at home, work or school. The second genetic
      factor is more specific to drug use and represents a general liability towards
      drug use, illicit or otherwise. The third genetic factor is specific to the
      alcohol use items only. The observed co-morbidity of alcohol and drug misuse can
      be attributed largely to a non-shared environmental factor common to both
      domains. Genetic co-morbidity appears to be limited to alcohol and substance
      misuse behaviours that interfere with normal daily functioning.

PMID- 7580822
TI  - The preparedness to share injecting equipment: an analysis using vignettes.
AB  - This paper reports on the use of vignettes to study drug injectors' preparedness
      to share injecting equipment. Separate vignettes referring to borrowing and
      passing on injecting equipment have been submitted to 505 injecting drug users in
      Glasgow. Injectors were asked to identify their own likely response in each of
      the situations described within the vignettes. It was shown that even among those
      injectors not reporting any actual sharing in the last 6 months a significant
      proportion would still be prepared to share injecting equipment within certain
      situations. The preparedness to share injecting equipment was seen to be
      influenced by such factors as social distance, sex and length of time injecting.
      It is suggested that even in situations where drug injectors may have modified
      their behaviour in the direction of lower levels of reported sharing, a
      propensity to share may remain. This suggests the continuing need to provide
      injectors with easy access to sterile injecting equipment; in addition, services
      working with injecting drug users may need to focus not only upon actual sharing
      behaviour but also upon what we have described here as the preparedness to share.
      Indeed, the latter dimension should stand as a warning to services of the
      potential for sharing injecting equipment to increase in the future.

PMID- 7580823
TI  - Caffeine and psychomotor performance: a reply to James.

PMID- 7580824
TI  - Nitrous oxide and the terminology of 'abuse' and 'use'.

PMID- 7580825
TI  - Special issue on AIDS.

PMID- 7580826
TI  - Pending problem of "silent" human immunodeficiency virus infection.
AB  - The problem of "silent" HIV infection is reviewed. Overall, the number of proven
      "silent" infection in several at-risk populations, including HIV exposed health
      care workers, homosexuals, IV drug addicts and children born to HIV-infected
      mothers, has been very low. Contrary to these observations, we describe a very
      high prevalence of HIV specific immunity and positive HIV specific PCR signals in
      an Ethiopian immigrant population recently arrived in Israel. The interpretation
      of these findings is not entirely clear but we suggest that host immunity and
      probably different handling of the infection may account for the longer
      persistence of viral components in the body. Further studies are required to
      determine the amount and nature of these viral elements and, most importantly,
      whether they are still infectious.

PMID- 7580828
TI  - Kaposi's sarcoma in patients infected with human virus (HIV): an overview.
AB  - The emergence of Kaposi's sarcoma (KS) among patients with HIV infection has
      raised a number of unsolved questions. The particular epidemiology and the
      etiology of KS remain unclear while both inflammatory cytokines and HIV-derived
      proteins appear to be involved in its pathogenesis as shown with the aid of in
      vitro KS-like cell cultures of animal models. Since KS rarely occurs among HIV
      positive Caucasian females, sexual hormones, especially beta Human Chorionic
      Gonadotropin, have recently been reported as providing theoretically some
      protection against KS both in vitro and in vivo. All these aspects will be
      detailed as well as the therapeutic approaches which still remain unsatisfactory.
      So far, there is no curative treatment for KS and drug-induced toxicity is the
      limiting factor for the prolonged use of the current approaches. Perspectives for
      therapy will be discussed.

PMID- 7580827
TI  - "Kinoids": the basis for anticytokine immunization and their use in HIV
      infection.
AB  - HIV infection is characterized, at least in part, by the dysregulation of the
      cytokine network. Both IFN gamma and IFN alpha are occasionally overproduced.
      These cytokines could participate in the HIV-induced immunosuppression. To enable
      a HIV-infected organism to promote an immune reaction against the virus, the
      immune competence should tentatively be restored by counteracting the
      overproduction of IFN alpha because of its well known antiproliferative
      properties. For this purpose, IFN alpha was chemically converted into a
      biologically inactive, but still immunogenic product, which we termed "kinoid",
      reminiscent of that of bacterial toxins which have been transformed into toxoids
      for vaccination. The "kinoid" derived from IFN alpha showed to be well tolerated
      and immunogenic, since its administration to experimental animals and humans
      should result in no untoward reactions, while eliciting the production of anti
      IFN alpha antibodies. Active "kinoid" immunization should permit to counteract
      the overproduction of the corresponding cytokine when involved in pathogenesis.
      Another alternative, although less attractive than active anti-kinoid
      vaccination, is passive immunization by administering anti-kinoid antibodies.
      Biological antagonists of cytokine, as well as gene therapy should also be taken
      into consideration.

PMID- 7580829
TI  - Internal transcriptional regulatory elements in HIV-1 and other retroviruses.
AB  - The transcriptional regulation of retroviruses plays an important role in their
      pathogenesis. Cis-acting elements have been identified in the long terminal
      repeat (LTR) at the 5' extremity of the integrated provirus. These elements
      determine the rate and the site of transcription initiation and consist of arrays
      of binding sites for transcription factors. Recent studies have demonstrated the
      presence of additional regulatory elements, located outside of the LTR, within
      the transcribed region of several retroviruses including avian and murine
      retroviruses, HIV-1, HTLV-1 and the human spumaretroviruses. This review
      describes these new observations and analyzes their significance both in terms of
      retroviral transcriptional regulation and in terms of pathogenesis.

PMID- 7580830
TI  - Factors associated with progression to AIDS and mortality in a cohort of HIV
      infected patients with hemophilia followed up since seroconversion.
AB  - Progression to AIDS and death were evaluated in 112 patients, 84 with hemophilia
      A and 28 with hemophilia B. Seroconversion period and age at seroconversion were
      similar in both groups. 36/112 patients died: 21/84 with hemophilia A (25%) and
      15/28 (54%) with hemophilia B. Mean survival time was 11.7 years. The 10-year
      cumulative survival was 75.8%. It was lower in hemophilia B (56.2%) compared to
      hemophilia A patients (82.4%; p = 0.002). 37 patients (33%) developed full-blown
      AIDS: 26 with hemophilia A (31%) and 11 with hemophilia B (39%). Mean AIDS-free
      survival time was 11.4 years. The 10-year cumulative AIDS-free survival was
      71.2%. It was 74.8% in hemophilia A and 60.3% in hemophilia B patients. CD4
      counts lower than 200/cmm occurred in 62 patients (56%): 45 with hemophilia A
      (54%) and 17 with hemophilia B (63%). The mean time to CD4 counts lower than 200
      was 9.4 years. Mean survival time in older seroconverters (35 year old or more)
      was shorter than in younger (9.5 vs. 11.7 years, p < 0.05). Mean CD4 cell counts
      at seroconversion were similar in hemophilia A and B patients and in different
      age classes at seroconversion. CD4 cell counts at seroconversion affected the
      survival: 90% seroconverters with CD4 cell counts of 800/cmm or more were alive
      at 10 years vs. 60% of seroconverters with CD4 cell counts lower than 800 (p <
      0.05).

PMID- 7580831
TI  - Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV
      positive patients at high risk of disease progression.
AB  - A randomized, placebo-controlled trial was designed to evaluate safety and
      immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients.
      This strategy was aimed to modulate the impaired cytokine regulation in AIDS.
      Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and
      with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted
      formol-inactivated interferon alpha-2a (IFN alpha) and continue the current
      antiretroviral treatment, whatever it was, or to receive the adjuvant alone and
      the current antiretroviral treatment. All patients received 4 i.m. injections
      monthly, followed by booster injections every 3 months. Clinical status,
      immunology and virology were monitored. Immune response to vaccination was
      evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha
      neutralizing capacity. Only local discomfort and transient fever were reported.
      All vaccines except one showed increased levels of anti-IFN alpha Abs and
      developed serum IFN alpha neutralizing capacity. Viral load did not increase in
      vaccinees while it remained unchanged or even increased in placebo-treated
      patients. None of them showed HIV-related symptoms and all had their CD4 cell
      counts stabilized over 18 months, whereas 2 placebo-treated patients developed
      full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic.
      Stable clinical and immunological status over 18 months was observed in vaccinees
      coupled to increased serum IFN alpha neutralizing capacity.

PMID- 7580832
TI  - Production in rabbits of high levels of anti-HIV-1 gp160 antibodies.
AB  - The production of anti-HIV-1 gp160 antibodies was obtained in rabbits given gp160
      either in saline or adsorbed onto calcium phosphate. Immunization with gp160 in
      saline induced the formation of antibodies directed to the p18 protein, whereas
      the gp160 adsorbed onto calcium phosphate elicited antibodies recognizing the
      gp160, p55, p25 and p18 proteins. Calcium phosphate was found to be a powerful
      adjuvant and it should be used for potentiating candidate anti-HIV vaccines.

PMID- 7580833
TI  - HIV-1 soluble antigens induced CD8+ cytotoxic T-cell responses in an immunized
      individual.
AB  - In an attempt to determine whether immunization of healthy HIV-1 seronegative
      individuals with a soluble gp160 candidate vaccine could induce an anti-HIV
      specific immune response, volunteers were immunized by two injections of a water
      in-oil emulsion containing a mixture of gp160 antigen together with selected
      peptides. Following immunization, lymphocytes were collected and stimulated in
      vitro with autologous HIV-1-infected cells. The results showed that immunization
      with soluble HIV-1 envelope was able to generate CD3+ CD8+ CTLs directed to gp160
      antigen. The CTL response was restricted to class I molecule HLA-A2. The CTL
      response was comparable to that elicited by immunization with HIV-1-envelope
      recombinant vaccinia virus.

PMID- 7580834
TI  - HIV-1 p17 synthetic peptide vaccine HGP-30: induction of immune response in human
      subjects and preliminary evidence of protection against HIV challenge in SCID
      mice.
AB  - An HIV-1 p17 subunit vaccine, HGP-30, was evaluated in 38 HIV-1 seronegative
      individuals in phase I clinical trials in U.K. and U.S.A. The vaccine preparation
      induced cytotoxic T-cell (CTL) (11/25) and lymphocyte proliferation responses to
      KLH (19/20) and HGP-30/p17 (24/29) as well as antibody responses to HGP-30
      (29/38) and KLH (38/38). The CTL activity was observed in a higher number of
      vaccine recipients (9/18) in the lower dose groups (10 and 25 micrograms/kg) than
      the vaccine recipients (2/7) in the 50 and 100 micrograms/kg dose group. These
      observations suggest that the 10-25 micrograms/kg vaccine dose may preferentially
      induce TH1 cell responses. TH1 cell responses have been suggested as important in
      inducing protective cell mediated immunity. The CTL response has been shown to be
      CD8+. In a pilot study in SCID mice, HIV-1 virus challenge studies in mice
      reconstituted with cells from an HGP-30 immunized individual showed protection
      against virus challenge as compared to SCID mice reconstituted with cells from a
      non-immunized subject. These studies suggest that HGP-30 is capable of inducing
      protective cellular immunity.

PMID- 7580835
TI  - Evidence for an antiviral effect and interferon neutralizing capacity in human
      sera; variability and implications for HIV infection.
AB  - The antiviral effect (AVE) and interferon neutralizing capacity (INC) of sera
      originating from either seronegative or HIV-infected individuals were determined.
      As a rule, sera from seropositive subjects exhibited higher AVE titers than sera
      from seronegative individuals. Similarly, the INC of sera from HIV-infected
      patients, was most often stronger than that of sera from seronegative
      individuals. Furthermore, sera from HIV-infected patients actively immunized with
      i-IFN alpha invariably expressed INC in response to treatment, which was not the
      case for sera from control unimmunized patients. All sera from HIV-infected
      patients were found by ELISA to contain antibodies specifically directed to IFN
      alpha.

PMID- 7580836
TI  - Impairment of circulating lactoferrin in HIV-1 infection.
AB  - Levels of plasma lactoferrin are decreased in HIV-1-infected patients in relation
      to the progression of the disease. Plasma lactoferrin concentrations were
      determined using a specific and sensitive enzyme immunoassay. 97 plasma were
      studied (22 asymptomatic, 45 symptomatic patients compared to 30 healthy
      controls) and the results showed a highly significant decrease (p < 0.001) of the
      level of lactoferrin in HIV-1-infected patients (respectively 2.79 +/- 1.2 and
      0.68 +/- 0.22 micrograms/ml) compared to controls (4.37 +/- 0.83 micrograms/ml).
      Since it is well established that plasma lactoferrin level could be influenced by
      the number of neutrophils, the experiments were reproduced in neutropenic
      patients who represent 10% of recruitment (6 among 45 symptomatic patients). The
      plasma from neutropenic symptomatic patients (neutrophils < or = 1,300/mm3)
      showed their mean lactoferrin level at 0.36 micrograms/ml still far above the
      normal values. In view of the different reported biological effects of
      lactoferrin that are of great importance in the non-specific defences, the real
      biological place of the lack of such a molecule could be one important component
      of the multifactorial nature of HIV-1 infection.

PMID- 7580837
TI  - Which nutrient supplements for optimal HIV-1 production by cultured human
      lymphocytes?
AB  - Under standard conditions, all established cell-lines of HIV-1-infected
      lymphocytes are cultured in a medium containing a high percentage of serum. We
      have found that whilst partial or total serum depletion impedes their cell
      growth, it dramatically increases their virus production. Serial subcultures in
      serum-depleted medium are necessary to insure permanent cell growth and a
      relatively high reverse transcriptase activity. Following optimization of culture
      conditions, both HIV-infected and uninfected H9 cells have been regularly grown
      in a new protein-free medium. Such chemically defined culture conditions were
      required to detect the effect of minor components, such as vitamins, on host cell
      virus interactions.

PMID- 7580839
TI  - Cytotoxic T lymphocytes specific for the synthetic VEINCTR peptide, a sequence
      found within the Fas molecule and env gp120 in the blood of HIV-1 seropositive
      individuals.
AB  - We have previously identified a VEINCTR peptide common to both the Fasmolecule
      and HIV-1 gp120. Here we report the characterization in PBMCs from HIV-1-infected
      individuals of a CD8+ class I restricted CTL activity directed towards this
      peptide. The peptide is highly conserved in various HIV-1 strains, being located
      at amino acid 287-293 (VEINCTR), within an epitope known as cell T epitope on the
      env protein of human immunodeficiency virus type-1. Cell cultures were obtained
      by polyclonal activation using autologous blast cells and CTL lines generated
      from frozen peripheral blood lymphocytes of HIV-1 seropositive donors by
      stimulation with the peptide and recombinant interleukin-2. The env-specific CTL
      turned out to kill autologous target cells infected with a recombinant vaccinia
      virus containing the env gene of HIV-1 or pulsed with peptide. Specificity was
      determined using shorter peptides. The CTL activity was directed against
      autologous target cells presenting the heptapeptide which is site located in the
      Fas molecule, known to be functionally involved in T-cell apoptosis.

PMID- 7580838
TI  - Contribution of alpha interferon (alpha IFN) to HIV-induced immunosuppression.
AB  - In the present investigation we have shown that PBLs taken from HIV-positive
      patients suppressed T-cell proliferation when cultured for at least 12 days. When
      infected In vitro with HIV-1, these cells become suppressive after 6 days. PBLs
      collected from seronegative individuals turned out to be non-suppressive even
      after prolonged culturing. However, when infected in vitro with HIV they were
      found to be cytostatic also after 6 days. This anti-immune activity, related to
      HIV infection, is mediated, at least in part, by alpha IFN, since about 50% of
      this HIV associated activity could be quenched by alpha IFN antibodies. We also
      showed that this T-cell cytostasis is associated with CD8+ cells. In view of a
      possible use of suppressive cells for T-cell vaccination, we verified that such
      cellular functions were abolished by aldehyde treatment.

PMID- 7580841
TI  - The applications of the polymerase chain reaction in the life sciences.
AB  - The polymerase chain reaction (PCR) allows the in vitro amplification of DNA
      fragments starting with tiny amounts of biological sample and oligonucleotide
      primers derived from sequence data. Since the technique is fast and easy, PCR has
      taken the DNA-technology to the routine laboratoria. We present a survey of the
      following applications of PCR: 1) The amplification of gene fragments as fast
      alternative of cloning. 2) The modification of DNA fragments. 3) The sensitive
      detection of pathogenic microorganisms, if desired followed by an accurate
      genotyping. 4) DNA analysis of arachaeological specimens. 5) The detection of
      mutations relevant for inherited diseases, malignant transformation or tissue
      typing. 6) The analysis of genetic markers for forensic applications, for
      paternity testing and for the mapping of hereditary traits. 7) The species
      specific amplification of DNA segments between interspersed-repeat elements. 8)
      The study of gene expression.

PMID- 7580840
TI  - HIV-1 gp120/160 expressing cells upregulate HIV-1 LTR directed gene expression in
      a cell line transfected with HIV-1 LTR-reporter gene constructs.
AB  - The results described in this paper demonstrate that HIV-1 gp120 can upregulate
      gene expression directed by the HIV-1 LTR. Briefly, exposing responder CD4+CEM-T4
      ID5 cells to stimulator CEMgp120/160 expressing cells (stably transfected with
      HIV-1 LTR-CAT and HIV-1 gp160, respectively) resulted in the increased synthesis
      of the CAT enzyme. Control non-transfected CEM-T4 cells did not induce the
      synthesis of CAT. In addition, when the responder cell line, U937-1C5 which also
      contains stably transfected HIV-1 LTR-CAT plasmid was exposed to irradiated CEM
      gp120/160 cells, there was no synthesis of the CAT enzyme. Neither recombinant
      gp120 nor gp160 were able to stimulate the synthesis of CAT in the responder
      cells. These results indicate that the mechanism by which gp120/160 expressed on
      transfected cells increase CAT synthesis in responder cells may be dependent on
      the manner which the protein is presented in association with accessory
      molecules. Moreover, recombinant soluble CD4 and anti-CD4 monoclonal antibodies
      inhibited CEM gp120/160 induced expression of HIV-1 LTR-directed expression in
      CEM-1D5 cells. Based on these results we hypothesize that HIV or its envelope
      protein, gp120, upon interaction with its receptor, the CD4 molecule on T helper
      cells, transduces a signal which translates into the upregulation of the gene
      expression directed by the HIV-1 LTR.

PMID- 7580842
TI  - Nucleic acid amplification and related techniques in microbiological diagnostics
      and epidemiology.
AB  - The use of nucleic acid amplification techniques within the medical microbiology
      laboratory is becoming more and more accepted. Polymerase chain reaction (PCR)
      tests or nucleic acid sequence based amplification (NASBA) assays are already
      available in the form of commercial kits. Although the technology has been
      adapted for application in a routine diagnostic setting, some of the systems'
      characteristics are still amenable to improvement. In this communication several
      of these aspects will be discussed. Reproducibility of DNA amplification mediated
      diagnostics and quality control of tests aiming at detection or genetic typing of
      both viral and bacterial microorganisms, will be discussed. This will be
      exemplified by the results obtained in multicenter studies on PCR diagnostics of
      the hepatitis viruses HBV and HCV and by data gathered in the course of PCR
      mediated DNA fingerprinting of Staphylococcus aureus strains, also performed in
      different institutes. Application of related techniques such as direct sequencing
      of amplified (c)DNA or the development of species-specific DNA probes will be
      described.

PMID- 7580843
TI  - Detection and identification of Campylobacter spp. using the polymerase chain
      reaction.
AB  - Since Campylobacters have fastidious growth requirements and conventional
      detection and identification requires at least 4-6 days, the development of fast
      but reliable detection procedures is needed. Although methods based on DNA probe
      technology have been developed, these are not sensitive enough for the detection
      of Campylobacter spp. in food products. Therefore a PCR procedure based on the
      amplification of the 16S rRNA gene was developed that specifically detects the
      thermophilic Campylobacter species. This assay provides an excellent tool for the
      rapid and sensitive isolation and identification of Campylobacter spp. from
      chicken samples. In order to further identify the different Campylobacter spp.,
      which are difficult to distinguish by conventional methods, PCR mediated
      approximately DNA typing was used to select species-specific DNA probes. This
      combination of PCR fingerprinting and probe hybridization results in a highly
      specific identification assay and provides an example of specific test
      development without the prior need for DNA sequence information. PCR mediated DNA
      typing was also used to study the epidemiology of diarrheal diseases caused by
      Campylobacter spp. Using primers complementary to dispersed repetitive DNA
      sequences and arbitrarily chosen DNA motifs PCR fingerprinting has proven to be a
      fast, highly discriminative and relatively simple method that can be applied in
      epidemiological investigations on Campylobacter infections. Besides this
      application of PCR fingerprinting for typing of Campylobacter spp. this method
      can also be used for the development of specific DNA probes.

PMID- 7580844
TI  - PCR and non-isotopic labeling techniques for plant virus detection.
AB  - PCR technology permits the detection of viruses at levels several orders of
      magnitude lower than is possible by other methods. This high sensitivity
      facilitates detection of virus sequences during the early stages of infection of
      plants and in soil and vector samples. Early detection of beet necrotic yellow
      vein virus (BNYVV) in Beta vulgaris is an important part of the strategy for
      prevention of the spread of rhizomania, a commercially significant disease of
      sugar beet. A diagnostic test for BNYVV has been developed. This test involves
      amplification of the viral genome by PCR coupled with non-isotopic labeling and
      detection of specific sequences. The PCR amplification of BNYVV sequences has
      been optimized with respect to primer design, sample preparation and reaction
      conditions. Several non-isotopic labeling strategies for signal amplification
      have been compared. Hybridization with digoxigenin-labelled cDNA permits the most
      sensitive detection of PCR products and is the most appropriate method for
      routine diagnosis. These observations are discussed in the context of the
      application of PCR for detecting a wide range of viruses.

PMID- 7580845
TI  - Applications of random PCR.
AB  - Since the technique of PCR was developed in 1985 (Saiki et al). many new forms of
      applications have been described in the literature. Of particular interest are
      PCR approaches, allowing amplification of unknown sequences. In this review these
      approaches are generally termed "Random PCR"s. While "conventional PCR" in the
      form that was first described by Saiki et al. is utilized for the amplification
      and subsequent detection of specific DNA sequences, which are precisely
      characterized in length and sequence, Random PCR is either used for universal
      amplification of prevailing DNA or for amplification of unknown intervening
      sequences which are not generally defined in length or sequence. We depict
      criteria for discrimination between conventional PCR and Random PCR. Furthermore,
      we have compiled a classification system for Random PCR approaches based on
      differentiation by primer structure (degenerate--non-degenerate). According to
      this classification system a general overview of published Random PCR approaches
      is given. Future aspects of application of Random PCR are mentioned and
      commented. Own investigations, combining Random PCR with the technique of
      chromosome microdissection and thus allowing characterization of unknown
      chromosomes or chromosome fragments via FISH, are presented. Results are briefly
      summarized.

PMID- 7580846
TI  - Basics of quantitative PCR 1: image analysis and quantitation of PCR products.
AB  - The reproducibility of quantitative image analytic assessment of agarose gel
      separated PCR products was tested in a computerised core facility image analysis
      unit serving several research groups. Routine type use of the instrumentation
      showed considerable variation (measurements of individuals bands: CV about 20%;
      ratio measurements: CV about 6.5%). Careful concentration on the methodology
      improved the result (CV about 9% and 4.5%, respectively). Focusing into the
      methodology clearly showed that the baseline correction was necessary. The
      magnification of the image and the width of the measurement window were important
      variation sources. If these were kept constant, the reproducibility improved
      remarkably (CVs of 1.69% and 2.90%, respectively). Further analysis showed that
      the results did not change during the warm up period of the instrumentation.
      Measurements based on integrated optical density or related variables were well
      correlated, but did not show linear relation with peak height estimates. The most
      reproducible results were achieved when the thresholds were placed at the point
      of 45 degrees inclination of the image density curve of the band, or at the half
      height points of the curve.

PMID- 7580847
TI  - Quantitative analysis of lymphokine mRNA expression by an automated, non
      radioactive method.
AB  - Variable gene expression, thus giving rise to variable mRNA levels, constitutes a
      major mechanism for controlling cell development and cell function. In order to
      investigate these changed mRNA levels, a sensitive and quantitative assay is
      required. A quick and easy method is described to quantify specific mRNA's by a
      combination of the polymerase chain reaction (PCR) and an electro
      chemiluminescenct (ECL) detection of the amplified products. Total cellular RNA
      is reverse transcribed and amplified with a biotinylated forward primer and a TBR
      (Tris (2,2'-bipyridine) ruthenium (II)) labelled reverse primer. The
      amplification product is captured on streptavidin-coated paramagnetic beads and
      quantified by ECL detection using the QPCR system 5000. The results can be
      converted to quantitative values with an external standard curve. In the present
      study, cytokine mRNA expression in T lymphocytes was quantified. Cytokine mRNA
      was measured at the attomolar range in a dynamic range up to three orders of
      magnitude. The ECL detection is quantitative, rapid and accurate.

PMID- 7580848
TI  - Optimization of the PCR test for the mutation causing bovine leukocyte adhesion
      deficiency.
AB  - The recent emergence of the bovine leukocyte adhesion deficiency (BLAD)
      demonstrated the risks of narrowing the genetic basis of a population. About 6%
      of the Holstein-Friesian cattle now descends from one bull who was a heterozygous
      BLAD carrier. Crossing his descendants resulted in the birth of homozygous BLAD
      calves with a life expectancy of < 1 year. The BLAD syndrome is caused by a point
      mutation in the gene coding for CD18, a subunit of the beta 2 integrins on the
      surface of leukocytes. By using a PCR-RFLP test, large numbers of cattle are now
      being screened in several countries to eradicate the mutant allele. We describe
      an optimization of the PCR primer set that has led to an improvement of the test.

PMID- 7580849
TI  - Rapid typing of 4 VNTR loci, 3'ApoB, MCT118,St14 and YNZ22 by the polymerase
      chain reaction of a Greek sample.
AB  - Allelic data from a Greek sample of unrelated individuals for the D17S30, 3'ApoB,
      D1S80 and DXS52 loci were obtained by the PCR and subsequent analysis with
      agarose gel electrophoresis. The distribution of observed genotypes is in
      agreement with expected values according to the Hardy-Weinberg equilibrium. An
      heterozygosity of at least 76% was demonstrated with 11-13 alleles for each
      locus. The use of the combination of the four loci could be a powerful tool for
      paternity testing and individual discrimination, in combination with the fact
      that PCR needs a minimal amount of DNA and is a very quick and sensitive method.

PMID- 7580851
TI  - PCR-VNTRs (PCR-Variable Number of Tandem Repeats) in forensic science.
AB  - PCR-VNTRs are important markers for the individualization in forensic science.
      Before their use in routine case work extensive validation studies such as
      population genetics, mutation rates and experimental sensitivity studies have to
      be carried out. Different applications of PCR-VNTRs in stain analysis, even with
      difficult stain material such as hair shafts and only a few sperm cells are
      demonstrated. The different extent of sequence heterogeneity in STR systems was
      verified by Taq-cycle-sequencing. STRs can be divided into systems with a
      constant (HumTH01), variable (HumVWA) and highly variable (HumACTBP2) sequence
      structure. As a consequence some STR systems are not only characterized by their
      length polymorphism, but also by a highly variable sequence polymorphism.

PMID- 7580850
TI  - Cloning novel alfalfa cyclin sequences--a RACE-PCR approach.
AB  - Cyclins are a complex group of proteins involved in regulation of the eukaryotic
      cell division cycle via their interaction with cyclin dependent kinases (Cdks).
      Cyclin gene sequences have been cloned from a number of plant species, including
      alfalfa, but the diversity of these genes suggests that there are many plant
      cyclins which have yet to be characterized. A RACE-PCR strategy has been adopted
      for cloning cyclin gene sequences expressed during direct somatic embryogenesis
      in alfalfa. RT-PCR with nested degenerate primers was used to amplify the highly
      conserved "cyclin box" region of a novel A-like cyclin mRNA sequence expressed
      after induction of somatic embryogenesis. The sequence of this PCR product was
      used to design primers for 5'- and 3'-RACE protocols. 5'-RACE using a modified
      SLIC (single strand ligation to single stranded cDNA) procedure revealed
      considerable sequence heterogeneity in the N-terminal region of the coding
      sequence with several closely related sequences apparent. Conventional 3'-RACE
      generated a single cyclin sequence. The complete coding sequence of one member of
      this A-like cyclin subgroup has been obtained by this RACE strategy and confirmed
      by PCR amplification and sequencing of alfalfa genomic DNA.

PMID- 7580852
TI  - Detection of hepatitis C viral RNA: comparison of Amplicor single PCR and nested
      set PCR processes with HCV serology for hemodialyzed patients.
AB  - Multicentre quality control studies demonstrated that optimization and
      standardization of HCV RNA reverse transcription polymerase chain reaction (RT
      PCR) amplification techniques were possible: thus, a nested HCV RNA RT-PCR assay
      was described as a reliable tool for the detection of hepatitis C viral RNA.
      Besides this, another procedure, the Amplicor HCV RNA qualitative test, a
      standardized RT-PCR assay, became available. In order to assess the relationship
      between seropositivity and potential infectivity and to compare both RT-PCR
      assays, all patients undergoing maintenance hemodialysis were evaluated at
      hospital de Meaux (Meaux, France) during one year. We conclude that both assays
      are equally sensitive and that acid guanidinium thiocyanate based methods, which
      are used to prepare RNA prior to PCR, are more efficient than the usual phenol
      extraction protocols. Care should be taken with sera from hemodialyzed patients
      as the presence of inhibitors of the PCR has been demonstrated during the course
      of HCV RNA testing.

PMID- 7580853
TI  - Improvement of cervical Chlamydia detection in asymptomatic family planning
      attendees by using Amplicor Chlamydia trachomatis assay.
AB  - We evaluated the Amplicor C. trachomatis PCR assay (Roche Molecular Systems,
      N.J.) for the diagnosis of cervical infection in asymptomatic women attending a
      family planning clinic, aged between 18 and 25 years. Culture onto McCoy cells
      with fluorescent monoclonal staining was the reference system. Cervical specimens
      from 485 women were tested. The prevalence of C. trachomatis was 10.5% by culture
      and 11% by Amplicor. No specimen was positive by culture and negative by PCR.
      Three PCR-positive, culture-negative specimens were positive by MOMP-PCR and a
      second plasmid-based PCR. The resolved sensitivity of PCR and culture were 100%
      and 94.5%, respectively. Specificities for both were 100%, positive and negative
      predictive values for culture were 100% and 99.3%. Total test efficiency was
      99.4%. The Amplicor C. trachomatis assay gave very clear results, quite above or
      below the cut-off value, and showed high sensitivity and specificity, improved
      ease of handling and represented a good alternative to culture for large scale
      diagnosis of asymptomatic C. trachomatis infection.

PMID- 7580854
TI  - Nucleoside diphosphate kinase from pea chloroplasts: purification, cDNA cloning
      and import into chloroplasts.
AB  - Nucleoside diphosphate kinase (NDPK; EC 2.7.4.6) was enriched 1900-fold from
      purified pea (Pisum sativum L. cv. Golf.) chloroplasts. The active enzyme
      preparation contained two polypeptides of apparent molecular weight 18.5 kDa and
      17.4 kDa. Both proteins were enzymatically active and were recognized by an
      antiserum raised against NDPK from spinach chloroplasts, suggesting the existence
      of two isoforms in pea chloroplasts. The N-terminal protein sequence data were
      obtained for both polypeptides and compared with the nucleotide sequence of a
      cDNA clone isolated from a pea cDNA library. The analysis revealed that the two
      NDPK forms are encoded for by one mRNA, indicating that the lower-molecular
      weight form could represent a proteolytic breakdown product of the 18.5-kDa NDPK.
      The pea chloroplastic NDPK is made as a larger precursor protein which is
      imported into chloroplasts. The NDPK precursor is then processed by the stromal
      processing peptidase to yield the 18.5-kDa form.

PMID- 7580855
TI  - Mitochondrial citrate synthase from potato: predominant expression in mature
      leaves and young flower buds.
AB  - A cDNA clone encoding mitochondrial citrate synthase (EC 4.1.3.7), the first
      enzyme of the tricarboxylic-acid cycle, was isolated from potato (Solanum
      tuberosum L.) and expression of the enzyme analyzed. The deduced amino-acid
      sequence of the potato mitochondrial citrate synthase showed high similarity to
      known citrate synthases from fungi, mammals and Arabidopsis thaliana. The
      expression pattern of this clone was determined by Northern blot analysis.
      Expression was detected in all tissues analyzed. The highest level of expression
      was found in green flower buds. In photosynthetic tissues, stronger mRNA
      expression was detected in mature than in immature leaves. This rise in
      expression with leaf age was accompanied by an increase in citrate-synthase
      activity. Within flowers, expression was severalfold stronger in anthers than in
      ovaries, indicating a role of mitochondrial citrate synthase during anther or
      pollen development. A comparatively low level of transcript was detected in
      underground heterotrophic tissues, such as stolons, tubers and roots. When tubers
      were stored at low temperature (4 degrees C), mitochondrial citrate-synthase gene
      expression increased slightly. From the data obtained, we conclude that
      expression of the mitochondrial citrate-synthase gene is regulated by
      developmental and environmental factors. The relatively high expression in leaves
      is in line with the assumption that mitochondria play an important role in
      photosynthetically active tissues.

PMID- 7580856
TI  - Pherophorins: a family of extracellular matrix glycoproteins from Volvox
      structurally related to the sex-inducing pheromone.
AB  - Pherophorins are extracellular matrix (ECM) glycoproteins from Volvox that share
      homology with the sex-inducing pheromone. A novel pherophorin (pherophorin III)
      was characterized both with respect to expression pattern and proteolytic
      processing in vivo. Furthermore, it was shown that the pherophorins represent a
      protein family of ECM glycoproteins exhibiting a modular composition: their N
      terminally located domain is a homolog of a domain found in the ECM glycoprotein
      SSG 185. Together with SSG 185, pherophorin I is a main component of the cellular
      zone within the ECM. The Volvox genome contains a tandem arrangement of genes
      encoding pherophorin II-related polypeptides. Inhibition of proteolytic
      processing of pherophorin II and III in vivo appears to result in the suppression
      of sexual induction.

PMID- 7580857
TI  - Coproporphyrinogen III oxidase from barley and tobacco--sequence analysis and
      initial expression studies.
AB  - Coproporphyrinogen III oxidase (coprogen oxidase; EC 1.3.3.3) is part of the
      pathway from 5-amino-levulinate to protoporphyrin IX which is common in all
      organisms and catalyses oxidative decarboxylation at two tetrapyrrole side
      chains. We cloned and sequenced full-length cDNAs encoding coprogen oxidase from
      barley (Hordeum vulgare L.) and tobacco (Nicotiana tabacum L.). They code for
      precursor peptides of 43.6 kDa and 44.9 kDa, respectively. Import into pea
      plastids resulted in a processed tobacco protein of approx. 39 kDa, which
      accumulated in the stroma fraction. Induction of synthesis of recombinant
      putative tobacco mature coprogen oxidase consisting of 338 amino-acid residues in
      Escherichia coli at 20 degrees C result in a catalytically active protein of
      approx. 39 kDa, while induction of its formation at 37 degrees C immediately
      terminated bacterial growth, possibly due to toxic effects on the metabolic
      balance of tetrapyrrole biosynthesis. The plant coprogen oxidase gene was
      expressed to different extents in all tissues investigated. This is most likely
      due to the differing requirements for tetrapyrroles in different organs. The
      steady-state level of mRNA did not significantly differ in etiolated and greening
      barley leaves. The content of coprogen oxidase RNA reached its maximum in
      developing cells and decreased drastically when cells were completely
      differentiated. Functioning of the two photosystems apparatus requires the
      synthesis of all pigment and protein components during plant development. It is
      speculated that the enzymes involved in tetrapyrrole synthesis are
      developmentally rather than light-dependently regulated. Regulation of these
      enzymes also guarantees a constant flux of metabolic intermediates and avoids
      photodynamic damage by accumulating porphyrins.

PMID- 7580858
TI  - Adenosine diphosphate glucose pyrophosphorylase genes in wheat: differential
      expression and gene mapping.
AB  - A full-length cDNA clone representing the large (shrunken-2) subunit of ADP
      glucose pyrophosphorylase (AGP; EC 2.7.7.27) has been isolated from a cDNA
      library prepared from developing grain of hexaploid wheat (Triticum aestivum L.,
      cv. Chinese Spring). The 2084-bp cDNA insert contains an open reading frame of
      1566 nucleotides and primer-extension analysis indicated that the 5' end is 10
      nucleotides shorter than the mRNA. The deduced protein contains 522 amino acids
      (57.8 kDa) and includes a putative transit peptide of 62 amino acids (6.5 kDa).
      The similarity of the deduced protein to the small subunit of AGP and to other
      AGP genes from plants and microorganisms is discussed. Northern hybridisation
      shows that the Agp1 genes (encoding the small subunit in the wheat endosperm) and
      the Agp2 genes (encoding the large subunit in the wheat endosperm) are
      differentially expressed in the wheat grain. Transcripts from both gene sets
      accumulate to high levels in the endosperm during grain development with the
      majority of the expression in the endopsperm rather than the embryo and pericarp
      layers. Although enzyme activity is detected in developing grains prior to 10 d
      post anthesis, only the Agp1 genes are active at this time (the Agp2 genes are
      not expressed until 10 d post anthesis). The possibility that the enzyme
      expressed during early grain development is a homotetramer of small subunits is
      discussed. The Agp1 and Agp2 genes are arranged as triplicate sets of single-copy
      homoeoloci in wheat. The Agp2 genes are located on the long arms of chromosomes
      1A, 1B and 1D, about 80 cM from the centromere. The Agp1 genes have been mapped
      to a position just distal to the centromere on the long arms of chromosomes 7A,
      7B and 7D.

PMID- 7580861
TI  - Tomato contains two differentially expressed genes encoding B-type phytochromes,
      neither of which can be considered an ortholog of Arabidopsis phytochrome B.
AB  - Tomato (Solanum lycopersicon L.) contains two B-type phytochrome genes (PHYB1 and
      PHYB2). Fragments of these two PHYB were cloned following amplification by the
      polymerase chain reaction of a portion of their relatively well conserved 5'
      coding regions. Polypeptides encoded by these gene fragments exhibit 90% sequence
      identity. These two PHYB are independently expressed in organ-specific fashion.
      In mature plants, PHYB2 mRNA is most abundant in fruit and PHYB1 mRNA in expanded
      leaves. A phylogenetic analysis fails to establish which tomato PHYB is
      orthologous to either Arabidopsis PHYB or PHYD, the latter being a second B-type
      phytochrome. Instead, this analysis indicates that following the divergence of
      the Solanaceae and Brassicaceae from one another, a PHYB gene duplicated
      independently in each lineage. Consequently, Arabidopsis PHYB mutants cannot be
      considered strictly equivalent to the tomato tri mutants, which appear to be
      mutated at the PHYB1 locus. Similarly, other putative PHYB mutants might not be
      equivalent to those described for Arabidopsis and tomato. This situation
      complicates efforts to determine 'PHYB function' because there might be no one
      answer to this question.

PMID- 7580860
TI  - Isolation of a cDNA encoding a cytochrome b5 specifically expressed in developing
      tobacco seeds.
AB  - Polymerase chain reaction (PCR) was used to amplify transcripts encoding
      cytochrome b5 from cDNA synthesised from RNA isolated from developing seeds of
      tobacco (Nicotiana tabacum L.). The sequence of the amplified products indicated
      that the clones encoded a second form of tobacco cytochrome b5, different from
      that previously characterised (Smith et al. 1994, Plant Mol Biol 25:527-537).
      Rapid amplification of cDNA ends (RACE)-PCR was used to amplify the 5' and 3'
      ends of the transcript. Northern blotting and RNAse protection assays of RNA
      samples isolated from different tobacco tissues indicated that this second
      cytochrome b5 form was expressed only in developing seeds. Therefore, it seems
      likely that this message is the product of a tobacco cytochrome b5 gene
      specifically expressed in seeds.

PMID- 7580862
TI  - Acromegaly: unravelling a complex disease.
AB  - Acromegaly is a rare endocrine disorder characterized by growth hormone
      hypersecretion and is usually caused by a pituitary macroadenoma. It is
      associated with significantly increased patient morbidity and mortality.
      Molecular biological studies have implicated a causative role for oncogenic
      mutations (activating Gs alpha mutations and/or chromosomal 11q13 deletions) in
      less than 50% of cases. The cause(s) in the remaining 50% is speculative.
      Epidemiological evidence indicates that biochemical cure is achieved when mean GH
      levels are 5mU/l or less during a day-profile. This GH value correlates well with
      that required to normalize the serum IGF-1 concentration, a GH-dependent peptide
      which can be used to monitor the disease activity in acromegaly. Treatment must
      be carried out under the supervision of a dedicated endocrinologist and tailored
      to patients needs. The success of any treatment modality (surgery/pituitary
      irradiation/medical) depends on adenoma size and the extent of pretreatment GH
      hypersecretion. A combination of therapies is usually required to achieve
      satisfactory control of adenoma growth and GH hypersecretion. Octreotide, a
      synthetic analogue of native somatostatin, is particularly effective in
      controlling GH hypersecretion in this condition and the widespread introduction
      of a long-acting depot preparation is eagerly awaited. The development of true GH
      deficiency as a result of treatment is potentially worrying in view of its
      possible contribution to the increased incidence of cardiovascular mortality
      associated with hypopituitarism.

PMID- 7580863
TI  - Maternal protein restriction early or late in rat pregnancy has differential
      effects on fetal growth, plasma insulin-like growth factor-I (IGF-I) and liver
      IGF-I gene expression.
AB  - We determined whether the effects of maternal protein restriction at various
      stages of pregnancy on fetal growth are accompanied by parallel changes in the
      expression of insulin-like growth factor (IGF)-I and -II in the fetal rat.
      Pregnant Wistar rats (5-7 per group) fed a low (5%) protein diet throughout
      gestation or during the last week only of gestation had decreased body weight
      gain, serum IGF-I, and liver IGF-I peptide and mRNA concentrations compared to
      control dams fed a normal (20%) protein diet. In contrast, dietary protein
      restriction during the first 2 weeks followed by the normal diet during the last
      week of pregnancy had no effect on these maternal indices at term. Pups born from
      dams fed the low protein diet during the last week only (P5-3d week pups) or
      throughout gestation (P5-pups) had lower birth weight (-11%; P < 0.05, and -22%;
      P < 0.001, respectively) and lower liver weight (-13%; P < 0.05, and -29%; P <
      0.001) than control pups (P20-pups). Plasma IGF-I, liver IGF-I, and liver IGF-I
      mRNA concentrations were reduced in both P5-3d week pups (by 34%, 31% and 26%,
      respectively) and P5-pups (by 56%, 66% and 44%, respectively). In contrast, short
      or long-term maternal protein restriction had no effect on neonatal plasma IGF
      II peptide and liver IGF-II mRNA concentrations. When imposed only during the
      first 2 weeks of gestation, maternal protein restriction had no effect on growth
      or IGF-I and IGF-II expression in newborn pups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580865
TI  - Role of IGF-I in the control of GH secretion in rainbow trout (Oncorhynchus
      mykiss).
AB  - To study the role of IGF-I on GH secretion, we looked firstly for IGF-I binding
      sites in the central nervous system. IGF-I presents a single class of binding
      sites on brain membranes and pituitary extracts. Their affinity constants (Ka)
      were 11.44 +/- 4.66 and 4.42 +/- 1.37 x 10(9) M-1, respectively and their
      capacity (Bmax) were 119.83 +/- 46.21 and 73.65 +/- 20.87 fmoles/mg,
      respectively. In a second step IGF-I and bGH action on GH release was tested in
      vitro and in vivo. IGF-I inhibited GH release by pituitary cell cultures while
      bGH did not, suggesting direct action of IGF at the pituitary level and indirect
      action of GH, possibly mediated by IGF-I. IGF-I injected into catheterization
      fish induced a rapid inhibition of GH release, while bGH induced a delayed one.
      This timing supports a direct effect of IGF-I on GH release and the indirect
      effect of bGH. So peripheral IGF-I can play a role on GH secretion, perhaps as a
      mediator of GH action. This could explain the delayed fluctuation of GH and IGF-I
      plasma levels previously observed. This strong relationship between plasma IGF
      and GH secretion in trout seems to be different from that in mammals in which
      systemic IGF does not seem to play a predominant role in regulating GH secretion.

PMID- 7580864
TI  - The First International Standard for Somatropin: report of an international
      collaborative study.
AB  - Following an earlier decision to move away from the in vivo bioassay for
      determination of the potency of therapeutic somatropin (recombinant DNA human
      growth hormone), 18 laboratories in 12 countries participated in an international
      collaborative study designed to establish an international standard for
      somatropin, calibrated both by bioassay and by physicochemical assays of
      somatropin content. The mean in vivo biological potency of preparation studied,
      coded 88/624, was 6.75 IU/ampoule (fiducial limits 6.30-7.23). Determination of
      the protein content by quantitative amino-acid analysis yielded a mean estimate
      of 1.98 mg protein per ampoule. (Relative standard deviation = 2.88%). Data from
      the study also yielded mean values of 97.2% +/- 0.8% for the monomer content of
      the preparation, and 8.18 (RSD = 4.00%) for A1% at 276 nm. At its 45th meeting,
      in October 1994, the ECBS of WHO formally established the preparation 88/624 as
      the First International Standard for Somatropin, with a defined content of 2.0 mg
      protein per ampoule, and a defined specific activity of 3.0 International Units
      per milligram.

PMID- 7580859
TI  - An amino-terminal deletion of rice phytochrome A results in a dominant negative
      suppression of tobacco phytochrome A activity in transgenic tobacco seedlings.
AB  - Overexpression of phytochrome A results in an increased inhibition of hypocotyl
      elongation under red and far-red light. We used this approach to assay for the
      function of N-terminal mutations of rice (Oryza sativa L.) phytochrome A.
      Transgenic tobacco seedlings that express the wild-type rice phytochrome A (RW),
      a rice phytochrome A lacking the first 80 amino acids (NTD) or a rice phytochrome
      A with a conversion of the first 10 serines into alanine residues (S/A) were
      compared with untransformed wild-type tobacco (Nicotiana tabacum L. cv. Xanthi)
      seedlings. Experiments under different fluence rates showed that RW and, even
      more strongly, S/A increased the response under both red and far-red light,
      whereas NTD decreased the response under far-red light but hardly altered the
      response under red light. These results indicate that NTD not only lacks residues
      essential for an increased response under red light but also distorts the wild
      type response under far-red light. Wild-type rice phytochrome A and, even more
      so, S/A mediate an enhanced phytochrome A as well as phytochrome B function,
      whereas NTD interferes with the function of endogenous tobacco phytochrome A as
      well as that of rice phytochrome A when co-expressed in a single host.
      Experiments with seedlings of different ages and various times of irradiation
      under far-red light demonstrated that the effect of NTD is dependent on the stage
      of development. Our results suggest that the lack of the first 80 amino acids
      still allows a rice phytochrome A to interact with the phytochrome transduction
      pathway, albeit non-productively in tobacco seedlings.

PMID- 7580867
TI  - Effects on neonatal growth of the Hba(th-j) deletion on mouse chromosome 11 are
      not due to genomic imprinting.
AB  - The Hba(th-j) deletion is found proximally on mouse chromosome 11 in a region of
      the genome that contains imprinted sequences important for neonatal growth
      regulation. This study has examined the effect of genomic imprinting on neonatal
      growth of offspring heterozygous for the Hba(th-j) deletion. Transmission of the
      deletion through both the male and female germ lines has shown that offspring
      heterozygous for the deletion are growth retarded when compared to wild type
      litter mates. This growth retardation is associated with the heterozygous
      genotype regardless from which parent the deletion is inherited. Growth of both
      wild type and Hba(th-j)/+ neonates born from Hba(th-j)/+ mothers is compromised
      when compared to offspring from wild type mothers indicating a maternal effect of
      the deletion on neonatal growth. These data demonstrate that sequences present in
      the Hba(th-j) deletion are important for growth regulation but that the
      expression of these sequences is not regulated by genomic imprinting.

PMID- 7580866
TI  - Characterization of the insulin-like growth factors (IGF) axis in a cultured
      mouse Leydig cell line (TM-3).
AB  - Characterization of the insulin-like growth factor (IGF) axis in a cultured mouse
      Leydig cell line (TM-3) was performed. Radioimmunoassayable IGF-I and IGF-II
      concentrations in TM-3 conditioned media (CM) were below the assay detection
      levels. Affinity cross-linking of IGF-I and IGF-II to crude membranes prepared
      from TM-3 cells revealed both type 1 and type 2 receptors and a 31 kDa IGF
      binding protein (IGFBP). Immunoprecipitation of solubilized crude membranes
      indicated that the 31 kDa protein was membrane associated IGFBP-4. Western ligand
      blots of CM from TM-3 cells demonstrated the presence of 24 and 28 kDa bands as
      major IGFBPs, and 25, 40, and 44 kDa as minor ones. The 28 kDa band could be
      invisible after Endoglycosidase-F treatment, suggesting that the 28 kDa IGFBP was
      a glycosylated form of IGFBP. The 24 kDa and 28 kDa bands were immunoprecipitated
      with an antibody to IGFBP-4. Treatment of TM-3 cells with IGF-I increased the
      levels of the 24 kDa IGFBP-4, as well as 25, 28, 40, and 44 kDa IGFBPs. IGF-I
      treatment also resulted in the appearance of a 29 kDa IGFBP. Neither the 25 nor
      29 kDa bands were deglycosylated with Endoglycosidase-F nor immunoprecipitated by
      antibodies to rIGFBP-1 and -2. On the other hand, IGF-II treatment resulted in a
      significant decrease in the 24 kDa IGFBP-4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580868
TI  - Increased plasma insulin-like growth factor-I (IGF-I) following oral and
      intraperitoneal administration of growth hormone to rainbow trout, Oncorhynchus
      mykiss.
AB  - Changes in plasma insulin-like growth factor-I (IGF-I) and growth hormone (GH)
      levels in rainbow trout, Oncorhynchus mykiss, were investigated after either
      intraperitoneal or oral (intragastric) administration of salmon GH. Plasma IGF-I
      and GH levels were measured by homologous radioimmunoassays for salmon IGF-I and
      GH. After intraperitoneal injection of salmon GH at doses of 0.1 or 1.0
      micrograms/g body weight to rainbow trout, plasma GH levels increased to a
      maximum after 6 h and declined rapidly thereafter. Plasma IGF-I levels were
      elevated after 12 h, reaching maximum at 24 h and (after the higher dose of GH)
      remaining high at 78 h after GH injection. In contrast, following intragastric
      administration of salmon GH at the same doses, plasma GH levels were
      significantly elevated 12 h after administration, reaching a maximum at 15 h and
      declining to basal levels at 24 h. Plasma IGF-I levels increased significantly
      after 48 h and remained elevated (after the higher dose of GH) for more than 96
      h. Effects on plasma GH and IGF-I were dose-dependent notwithstanding the route
      of administration of GH. These results indicate that plasma IGF-I in salmonid
      fish is under GH control and that oral administration of the hormone is followed
      by longer-lasting effects than those achieved by intraperitoneal injection.

PMID- 7580869
TI  - A brief appraisal on some aspects of the receptor-receptor interaction.
AB  - Receptor-receptor interaction is being recognized as a key cellular mechanism
      responsible for the integration of signals between different transmission lines
      at the membrane level. Receptor-receptor interaction extends the classical
      concept of integration of depolarization and hyperpolarization effects to the
      integration of chemical events at membrane level. In the present paper only some
      hypotheses on the possible mechanistic aspects of the interactions between the
      membrane receptors will be discussed. Furthermore, possible functional
      consequences of receptor-receptor interaction will be explored. The limitations
      of the present experimental approaches to the study of receptor-receptor
      interaction will also be analysed.

PMID- 7580871
TI  - Regulation of GTP cyclohydrolase I gene expression and tetrahydrobiopterin
      content by nerve growth factor in cultures of superior cervical ganglia.
AB  - Monolayer cultures of superior cervical ganglia free of support cells were
      maintained in the presence of 100 ng/ml 7S-NGF for 4 days. The concentration of
      NGF was then changed to between 50 and 400 ng/ml and cultures continued for an
      additional 7 days. Tetrahydrobiopterin (BH4) content, GTP cyclohydrolase (GTPCH)
      enzyme activity and mRNA levels were then determined. All three of these measures
      were found to be elevated between 2- to 4-fold by treatment with increasing
      concentrations of NGF. Tyrosine hydroxylase (TH) enzyme activity and mRNA levels
      were increased from 8 to 13-fold by these same treatments. These results indicate
      that the content of BH4 within sympathetic neurons can be regulated by NGF
      receptor-mediated changes in GTPCH gene expression. Moreover, concomitant
      increases in TH enzyme activity and BH4 content demonstrate a coordinated
      regulation by NGF of this enzyme and its essential cofactor.

PMID- 7580873
TI  - Facilitation and inhibition of G-protein regulated protein secretion by
      melatonin.
AB  - Melatonin has been found to inhibit or enhance the constitutive secretion of
      proteins from the cultured melanoma cells at nanomolar concentrations (0.5-10
      nM), in a dose dependent manner. The amplitude and direction of the response were
      found to depend on cell density: melatonin inhibited the release early after
      plating or at low cell density, but facilitated the release later on, or at high
      cell density. To elucidate the involvement of G-proteins in these responses, the
      effects of guanosine 5'-O-(3-thiotriphosphate) (GTP tau S; which was introduced
      into the cells during the process of permeabilization and resealing with ATP),
      aluminum fluoride, pertussis and cholera toxins on protein secretion from the
      cells were assessed in the absence and presence of melatonin. At low cell
      density, melatonin inhibited release, but paradoxically enhanced it when GTP
      hydrolysis was blocked (by GTP tau S or cholera toxin treatment). Aluminum
      fluoride and melatonin inhibited protein release in the absence or presence of
      GTP tau S. At high cell density, melatonin facilitated the release and so did GTP
      tau S, aluminum fluoride, their combination, and cholera toxin treatment.
      However, in the presence of the combination of GTP tau S, aluminium fluoride and
      melatonin, protein release was paradoxically inhibited. Similar treatment of the
      cells with pertussis toxin, did not affect the melatonin-mediated inhibition or
      facilitation. These results indicate that the effects of melatonin on protein
      secretion are mediated by at least one heterotrimeric G protein which belongs to
      the Gs class. In addition, melatonin can facilitate secretion via a cholera and
      pertussis toxins-insensitive mechanism which can be inhibited by aluminum
      fluoride. This effect is manifested when Gs is permanently activated (by GTP tau
      S or cholera toxin).

PMID- 7580870
TI  - Melatonin biosynthesis in photoreceptor-enriched chick retinal cell cultures:
      role of cyclic AMP in the K(+)-evoked, Ca(2+)-dependent induction of serotonin N
      acetyltransferase activity.
AB  - The roles of cyclic AMP and calcium in the regulation of serotonin N
      acetyltransferase (NAT) activity were studied in low density monolayer cultures
      of chick retinal photoreceptors and neurons. Photoreceptor-enriched retinal cell
      cultures were prepared from embryonic day 6 retinas and cultured for 6 days. NAT
      activity in these cultures could be induced by treatment with cyclic AMP
      protagonists, 8Br-cyclic AMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX),
      or by treatment with depolarizing concentrations of extracellular K+. The
      stimulatory effect of K+, which involves Ca2+ influx through dihydropyridine
      sensitive channels, was mediated at least in part by cyclic AMP, as indicated by
      the following observations. Depolarizing concentrations of K+ stimulated the
      formation of cyclic AMP, and the stimulatory effects of K+ on both cyclic AMP
      formation and on NAT activity were synergistically potentiated by the cyclic
      nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). MDL
      12,330A, a putative adenylate cyclase inhibitor, inhibited K(+)-evoked cyclic AMP
      accumulation and induction of NAT activity over the identical concentration
      range. In contrast, MDL 12,300A failed to inhibit the induction of NAT elicited
      by 8Br-cyclic AMP. H-89, an inhibitor of cyclic AMP-dependent protein kinase,
      antagonized the induction of NAT activity by either forskolin or K+ with equal
      potency for both stimuli. These results suggest that cyclic AMP plays an
      essential role in the induction of NAT activity that occurs as a consequence of
      membrane depolarization. Cyclic AMP and Ca2+ may also interact at a step distal
      to adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7580872
TI  - Calcium responses of isolated, immunocytochemically identified rat pinealocytes
      to noradrenergic, cholinergic and vasopressinergic stimulations.
AB  - Calcium responses of isolated rat pineal cells to noradrenergic, cholinergic and
      vasopressinergic stimulations were recorded by use of the fura-2 technique and an
      image analysis system. Subsequently the recorded cells were identified as
      pinealocytes by immunocytochemical demonstration of S-antigen, a pinealocyte
      specific marker. S-antigen immunoreactive pinealocytes were shown to respond to
      norepinephrine stimulation with an elevation of the intracellular free calcium
      concentration ([Ca2+]i). This response was dose-dependent and consisted of a
      rapid increase in [Ca2+]i (primary phase) followed by a decrease to an elevated
      plateau well above the basal level (secondary phase). The plateau persisted for
      at least 1 h when cells were constantly exposed to norepinephrine and dropped to
      basal level upon removal of the stimulus. Analysis of the calcium responses of
      cells treated with caffeine or thapsigargin suggested that the primary phase
      reflects mobilization of calcium from inositol 1,4,5-trisphosphate-sensitive
      intracellular calcium stores. Depletion of these calcium stores was a decisive
      and sufficient prerequisite to evoke the secondary phase which was apparently
      elicited by calcium influx. These data suggest that a capacitative calcium entry
      is involved in pineal calcium signalling. Acetylcholine induced an increase in
      [Ca2+]i in rat pinealocytes. Experiments with different cholinergic agonists and
      antagonists provided evidence that the acetylcholine-induced calcium response was
      mediated via nicotinic acetylcholine receptors. Stimulation of isolated rat
      pineal cells with arginine-vasopressin caused a rise in [Ca2+]i in approx. 5% of
      the cells. However, these cells remained unidentified because they contained
      neither immunoreactive S-antigen nor immunoreactive glial fibrillary acidic
      protein, a marker for interstitial (glial) cells of the rat pineal organ. Taken
      together, the results underline the pivotal role of norepinephrine for the
      regulation of pineal signal transduction, but they also support the notion that
      other neurotransmitters and neuropeptides are involved in the modulation of
      pineal calcium signalling.

PMID- 7580874
TI  - In vivo studies on NMDA-evoked release of amino acids in the rat spinal cord.
AB  - In the present study, spontaneous and evoked release of selected amino acids in
      the rat spinal cord was studied using in vivo microdialysis. Perfusion of the
      microdialysis probe with 100 K+ evoked a 2-4-fold increase in release of the
      putative neurotransmitters aspartate, glutamate and taurine while glutamine was
      decreased. K(+)-evoked release of glutamate was almost completely Ca(2+)
      dependent while that of aspartate was partially Ca(2+)-dependent. Taurine release
      was not affected by substituting Ca2+ with Co2+. Perfusion with 5 mM N-methyl-D
      aspartate (NMDA) evoked 3-9-fold release of glutamate, glycine and taurine and a
      small increase in extracellular beta-alanine. No significant changes in glutamine
      and serine were found. 5 mM of the competitive NMDA antagonist 3-((+/-)-2
      carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced NMDA-evoked release
      of glutamate and taurine by approx. 50%. 5 mM 3-amino-1-hydroxypyrrolid-2-one (HA
      966), an agonist at the glycine site of the NMDA receptor with very low efficacy,
      completely inhibited NMDA-evoked release of taurine and reduced the levels of
      released glutamate below baseline, similar to the effect of 1 mM CPP alone. The
      present results show that in situations of excessive release of excitatory amino
      acids such as spinal ischemia and trauma. NMDA receptor-evoked release of
      glutamate may amplify the deleterious process and spread the damage.

PMID- 7580875
TI  - Secretion of methoxyindoles from trout pineal organs in vitro: indication for a
      paracrine melatonin feedback.
AB  - Synthesis and release of the pineal hormone melatonin is in all vertebrates
      primarily regulated by the light/dark cycle. In pineal organs of teleost fish,
      like in other non-mammalian vertebrates, melatonin formation is regulated by a
      direct photoreception of the pineal organ. We performed measurements in
      explanted, perifused pineal organs of the rainbow trout, Oncorhynchus mykiss, to
      examine whether melatonin can influence its own production. For this purpose we
      have continuously perifused isolated pineal organs under light- and dark-adapted
      conditions and measured the release of melatonin and other methoxy-indoles by
      HPLC with electrochemical detection. Addition of 2-iodomelatonin to the
      perifusate in a concentration of 2 ng/ml significantly inhibited melatonin
      release in light-, as well as in dark-adapted organs. The release of 5
      methoxytryptamine and 5-methoxytryptophol was also significantly reduced in light
      adapted organs. These results indicate that extracellular melatonin may act as a
      paracrine or autocrine feedback signal and may be important for the illumination
      dependent melatonin production.

PMID- 7580877
TI  - Nicotine enhances brain biopterin concentration in rats.
AB  - The dose-response and time-course effects of acute nicotine on total biopterin
      concentrations in the striatum, hypothalamus and hippocampus were examined in
      rats by using high performance liquid chromatography (HPLC) with fluorescence
      detection. Results indicated that across a wide dose range, only 0.5 mg/kg
      nicotine (free base) significantly increased biopterin level in the striatum and
      the hypothalamus, but not in the hippocampus. The time-course results revealed
      that the optimal time point for nicotine to exert this effect is around 30 min
      after systemic injection. These results suggest that nicotine may enhance
      catecholamine synthesis in these areas. It further implies that nicotine may
      alleviate the symptom of motor dysfunction as observed in certain neurological
      diseases.

PMID- 7580876
TI  - Acetylcholinesterase in tentacles of Octopus vulgaris (Cephalopoda).
      Histochemical localization and characterization of a specific high salt-soluble
      and heparin-soluble fraction of globular forms.
AB  - Transverse sections of Octopus tentacles were stained for acetylcholinesterase
      (AChE) activity. An intense staining, that was suppressed by preincubation in 10(
      5) M eserine, was detected in a number of neuronal cells, nerve fibres and
      neuromuscular junctions of intrinsic muscles of the arm. Octopus
      acetylcholinesterase was found as two molecular forms: an amphiphilic dimeric
      form (G2) sensitive to phosphatidylinositol phospholipase C and a hydrophilic
      tetrameric (G4) form. Sequential solubilization revealed that a significant
      portion of both G2 and G4 forms was recovered only in a high salt-soluble
      fraction (1 M NaCl, no detergent), Heparin (2 mg/ml) was able to solubilize G2
      and G4 forms with the same efficiency than 1 M NaCl. The solubilizing effect of
      heparin was concentration-dependent and was reduced by protamine (2 mg/ml). This
      suggests that heparin operates through the dissociation of ionic interactions
      existing in situ between globular forms of AChE and cellular or extracellular
      polyanionic components. Interaction of AChE molecular forms with heparin has been
      reported so far in only a few instances and its physiological meaning is
      uncertain. G2 and G4 forms, interacting or not with heparin, all belong to a
      single pharmacological class of AChE. This suggests the existence of a single
      AChE gene. Amphiphilic and hydrophilic subunits thus likely result either from
      the processing of a single AChE transcript by alternative splicing (as in
      vertebrate AChE) or from a post-translation modification of a single catalytic
      peptide.

PMID- 7580879
TI  - Amplification of RNA.

PMID- 7580880
TI  - Expression-PCR (E-PCR): overview and applications.

PMID- 7580881
TI  - Detection and differential display of expressed genes by DDRT-PCR.

PMID- 7580878
TI  - Construction of phagemid display libraries with PCR-amplified immunoglobulin
      sequences.

PMID- 7580882
TI  - Effect of internal direct and inverted Alu repeat sequences on PCR.
AB  - We have studied the effect of repeated DNA sequence, especially Alu repeats, on
      PCR. Alu repeats are sequences that are approximately 300 bp long and
      interspersed at a very high copy number throughout the human genome. We amplified
      part of the human low-density lipoprotein receptor gene containing two Alu repeat
      sequences in the same orientation, approximately 7.8 kb apart, with unique
      sequence primers outside these repeats. The major PCR product was a DNA fragment
      with an in vitro deletion between the Alu repeats. The formation of this product
      depended on the template concentration and the type of polymerase used. Such a
      product arose apparently as a result of a "jumping reaction" involving a primer
      whose extension was terminated prematurely within one Alu repeated followed by
      annealing of such an incompletely extended primer to the other, distant Alu
      repeat. No such jumping products were seen when a 0.8-kb region containing two
      nearby inverted Alu repeats within the human alpha-galactosidase A gene was
      subject to PCR with unique sequence primers annealing just outside these repeats.

PMID- 7580883
TI  - Reliability of PCR decontamination systems.
AB  - A major problem in the application of PCR is contamination with material
      amplified previously. Repeated PCRs result in the accumulation of intact and
      degraded amplicons and primer artifacts that can contaminate following
      amplification reactions. Post-PCR UV treatment and pre-PCR uracil DNA glycosylase
      (UDG) digestion have been recognized to efficiently inactivate or decompose
      intact amplification fragments. We show here that degraded amplification products
      and primer artifacts account for decreased sensitivity and may cause false
      negative results. Our experiments indicate that partly degraded PCR products and
      primer artifacts containing sequences homologous to the primer oligonucleotides
      in the succeeding PCR reaction compete efficiently with sample DNA for the
      primers. The experiments done in this study may explain unexpectedly low PCR
      sensitivities reported in an increasing number of publications. In an attempt to
      solve this problem, we evaluated three post-PCR treatment methods to completely
      eliminate sequences competing for the amplification primers, namely, 8
      methoxypsoralen (MOPS) or hydroxylamine treatment of amplified DNA and use of
      oligonucleotides containing 5'-ChemiClamps. However, all three methods did not
      sufficiently inhibit artificially produced carryover contaminations. In
      conclusion, false-positive results can be eliminated with UDG or UV treatment,
      but physical barriers are indispensable to avoid the occurrence of false-negative
      results.

PMID- 7580885
TI  - Rapid isolation of cDNA clones by aliquot testing via PCR amplification.

PMID- 7580884
TI  - Amplification of gene fragments with very high G/C content: c7dGTP and the
      problem of visualizing the amplification products.

PMID- 7580886
TI  - Assessment of colinearity between large cloned DNA fragments and genomic DNA.

PMID- 7580887
TI  - Use of vectorette and subvectorette PCR to isolate transgene flanking DNA.
AB  - Vectorette PCR permits the specific amplification of DNA segments flanking a
      known DNA sequence. It enables the application of the PCR where sequence
      information is only available for one primer site. We now show that vectorette
      PCR can be used for the systematic mapping and retrieval of transgene flanking
      DNA. We also show that the sequence of large vectorette PCR fragments can be
      obtained without cloning, by the production of subvectorette fragments.

PMID- 7580888
TI  - Detection of p53 gene mutation in cancer tissues by nonradioactive direct
      sequencing.
AB  - A simple procedure for direct sequencing of double-stranded PCR products by the
      dideoxy-termination method has been developed using biotinylated sequencing
      primers. Sequences of the p53 gene have been obtained from DNA extracted from
      frozen and formalin-fixed paraffin-embedded cancer tissues. Detection of
      sequencing ladders was done with chemiluminescent or colorimetric techniques.
      Both are highly sensitive, but colorimetric detection is less prone to diffusion
      artifacts, which are common in G-rich regions. Use of this nonradioactive PCR
      sequencing protocol allowed rapid and simple determination of p53 gene
      alterations in human tumors.

PMID- 7580889
TI  - Detection of HCV RNA by the asymmetric gap ligase chain reaction.
AB  - The ligase chain reaction (LCR) and the gap ligase chain reaction (gLCR) are
      exponential amplification techniques for the detection of DNA sequences in a
      sample. Both techniques depend on the enzyme, DNA ligase, to join adjacent probes
      annealed to a DNA molecule. However, DNA ligase joins DNA inefficiency on an RNA
      target. Consequently, LCR and gLCR cannot amplify RNA efficiency. RNA detection
      methods using LCR or gLCR require a cDNA synthesis step. The carryover of four
      dNTPs from the cDNA reaction inhibits gLCR. Although LCR can use cDNA reaction
      products directly, background generated by blunt-end ligation does not allow the
      high sensitivity typically needed for HIV or HCV detection. The asymmetric gap
      ligase chain reaction (AGLCR) is a modification of gLCR that allows for the
      detection of RNA by using < or = 3 of the 4 nucleotides in the cDNA step and the
      gLCR step. Fewer than 50 copies of synthetic RNA transcript can be reproducibly
      detected. HCV, an RNA virus with no DNA intermediate, was chosen as the initial
      RNA model system. HCV antibody-positive and normal samples were analyzed, and the
      results were found to correlate with the results obtained using nested RNA-PCR.
      AGLCR provides a new nucleic acid amplification technique that can aid in the
      diagnosis of disease when the detection of RNA is critical.

PMID- 7580890
TI  - PCR analysis of the H ferritin multigene family reveals the existence of two
      classes of processed pseudogenes.
AB  - The human gene coding for the apoferritin H subunit belongs to a complex
      multigene family constituted by the expressed gene and by an undefined number of
      pseudogenes. We have used a strategy based on PCR to amplify specifically the H
      pseudogenes from a sample of human genomic DNA. With this approach, three new H
      pseudogenes have been cloned and characterized by DNA sequence analysis. In
      addition, we have identified a new type of pseudogene, the size of which (700 bp)
      is caused by multiple detection events in the putative coding region.

PMID- 7580891
TI  - Analysis of nonspecific DNA synthesis during in situ PCR and solution-phase PCR.
AB  - In this study we examine the factors that lead to nonspecific DNA synthesis
      during in situ PCR and solution-phase PCR. It was shown that primer-independent
      DNA synthesis can produce an intense signal during in situ PCR. This primer
      independent pathway was apparently the result of the repair of DNA gaps induced
      by the heat treatment of the paraffin embedded tissue sections. This non-specific
      signal could be eliminated by blocking gap repair with dideoxy-TTP, avoiding heat
      treatment, or DNase pretreatment. The primer-independent signal was also
      influenced by the length and mode of fixation and the sample tissue itself.
      Elimination of the primer-independent signal and the use of viral primers in
      tissues that did not contain the virus showed that nonspecific DNA synthesis
      could be eliminated by the hot start modification. Primer oligomerization did not
      produce a signal during in situ PCR, even when it occurred robustly in the
      amplifying solution. Generation of the primer-independent signal in solution
      phase PCR with purified DNA required a cross-linking fixative, heating, the
      addition of bovine serum albumin, and intact protein-DNA cross-links.

PMID- 7580892
TI  - Parameters affecting the sensitivities of dideoxy fingerprinting and SSCP.
AB  - The goals of the present experiments are (1) to improve dideoxy fingerprinting
      (ddF) and (2) to utilize ddF as a tool to evaluate the relative merits of
      different conditions for single-strand conformation polymorphism (SSCP). ddF is
      performed by electrophoresing one dideoxy termination reaction through a
      nondenaturing gel. The ddF pattern can be divided into a "dideoxy component" and
      an "SSCP component". If dideoxy CTP (ddCTP) is utilized for the termination
      reaction of ddF, the dideoxy component is abnormal when an extra segment is
      produced by a sequence change that creates an extra C or when a segment is
      eliminated by a change of C to another base. All subsequent segments produced by
      the termination reaction constitute the SSCP component that contains the mutation
      in a nested series of ddCTP termination products. The SSCP component is
      informative if abnormal mobility is detected in one or more of the segments.
      Herein, we utilize 84 different single-base changes in the human factor IX gene
      to examine the effects of gel matrix, temperature, and different primers on the
      sensitivity of ddF. The effects of glycerol and cross-linker ratio were examined
      on fewer mutations. The following conclusions emerge: 1. The sensitivity of the
      dideoxy component is invariant, but the sensitivity of the SSCP component can
      vary greatly with gel matrix, temperature, segment size, and sequence context. 2.
      For a given segment containing a mutation, it is likely that a mobility shift
      will be seen under some conditions but not under other conditions. By examining
      the mobility of the SSCP component in > 2200 segments, it was found that some
      conditions are statistically more likely to result in altered mobility, thereby
      increasing the average sensitivity of mutation detection by ddF or conventional
      SSCP. 3. GeneAmp and MDE gels are superior to polyacrylamide gels and
      electrophoresis at 8 degrees C is superior to electrophoresis at 23 degrees C.
      GeneAmp at 8 degrees C provided the highest SSCP component efficiency of all
      conditions tested; all 84 hemizygotes and 40 heterozygotes were detected readily
      by ddF under these conditions. 4. The segments that terminate near the mutation
      site are likely to show an abnormal mobility on polyacrylamide gels at 23 degrees
      C. 5. The likelihood of mobility shifts decreases with segment size, but sequence
      context can have a major effect on SSCP component efficiency.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7580893
TI  - In vitro synthesis of novel genes: mutagenesis and recombination by PCR.

PMID- 7580894
TI  - Rapid PCR site-directed mutagenesis.

PMID- 7580895
TI  - Single-strand conformational polymorphism.

PMID- 7580896
TI  - Quality assurance and use of PCR in clinical trials.
AB  - Qualitative and quantitative HIV-1 DNA and RNA PCR assays are proving to be
      useful in the diagnosis of HIV-1 infection in infants and in assessing the in
      vivo antiviral activity of new therapies and regimens in clinical trials. The use
      of these standardized commercial assays in conjunction with an external quality
      assurance program has ensured that results from different laboratories are
      comparable. In addition, real-time proficiency monitoring has the potential to
      detect problems immediately before patient data are compromised.

PMID- 7580897
TI  - Alteration of hairpin ribozyme specificity utilizing PCR.
AB  - We have developed a method by which a researcher can quickly alter the
      specificity of a trans hairpin ribozyme. Utilizing this PCR method, two
      oligonucleotides, and any target vector, new ribozyme template sequences can be
      generated without the synthesis of longer oligonucleotides. We have produced
      templates with altered specificity for both standard and modified (larger)
      ribozymes. After transcription, these ribozymes show specific cleavage activity
      with the new substrate beta-glucuronidase (GUS), and no activity against the
      original substrate (HIV-1, 5' leader sequence). Utilizing this technique, it is
      also possible to produce an inactive ribozyme that can be used as an antisense
      control. Applications of this procedure would provide a rapid and economical
      system for the assessment of trans ribozyme activity.

PMID- 7580899
TI  - Quantitative analysis of gene expression in different tissues by template
      calibrated RT-PCR and laser-induced fluorescence.
AB  - RT-PCR is widely used to study gene transcription in many biological systems.
      Despite the development of a variety of, at times complex, procedures,
      quantitation of RT-PCR remains difficult, particularly when comparing RNA from
      different tissues or very small samples. In the procedure described here, we
      calibrate input cDNA through incorporation of trace label. PCR product is
      generated from equal amounts of cDNA with fluoresceinated primers, size
      fractionated, and quantitated by laser-induced fluorescence in an automated DNA
      sequencer. Eliminating variation in input cDNA resulted in reliable
      noncompetitive PCR quantitation from templates equivalent to > or = 50 pg of
      total RNA. Using the example of beta-glucuronidase, a low-copy-number
      housekeeping gene, we have drawn a map of differential gene expression for this
      protein in various rat tissues.

PMID- 7580900
TI  - Quantitation of mRNA species by RT-PCR on total mRNA population.
AB  - PCR is commonly used for mRNA quantitation. Previously described procedures are
      applied to one or a few specific mRNA sequences. We show here that methods used
      for amplifying heterogeneous cDNA populations can be applied to the quantitation
      of many mRNA species. This quantitation is achieved by dot blotting and
      hybridization with the corresponding probes after amplifying a bulk mRNA
      population. Only a single, two-round-amplification assay is required for
      quantitation of a whole set of mRNA species. The proportionality of input
      molecules to output signal was shown by performing a series of control
      experiments. We applied this technique to measure the relative variations of the
      MBP, Po, and MAG mRNA sequences in the normal trembler mouse model. The results
      were consistent with previously described Northern blot data. This quantitative
      PCR method provides a rapid and reliable way to quantify relative amounts of mRNA
      species in small amounts of total RNA by using internal controls.

PMID- 7580898
TI  - Direct gene quantitation by PCR reveals differential accumulation of ectopic
      enzyme in rat-1 cells, v-fos transformants, and revertants.
AB  - Valid comparisons of gene promoter activities between different cell lines, and
      within a cell line, critically depend on accurate measurements of the number of
      genes introduced into the nuclei of cells. We have developed a simple method that
      allows direct and accurate quantitation of transfected plasmid DNA in cultured
      cells. The transfected DNA present in nuclei is copurified with genomic DNA
      without using phenol/chloroform extractions. DNA is amplified by PCR, and the
      amount of transfected DNA is read directly from a standard curve. By using the
      procedures described in this report, we have studied the relative expression of
      the Escherichia coli beta-galactosidase gene, driven by the wild-type Mo-MuLV
      LTR, in Rat-1 fibroblasts, FBJ v-fos-transformed Rat-1 (1302), and a revertant of
      v-fos-transformant (EMS-1-19) cell lines. The relative levels of expression of
      the transgene at 22 hr post-transfection in these three cell lines were 1:4:1,
      respectively, and at 48 hr post-transfection the respective ratios were 1:10.6:4.
      These results have significant implications for the use of cotransfected internal
      control plasmids to normalize data from transient transfection experiments to
      study promoter activities among different cell lines.

PMID- 7580901
TI  - A competitive deletion mutant quantitative PCR assay for angiotensin-converting
      enzyme mRNA in smooth muscle cells.
AB  - To quantify angiotensin-converting enzyme (ACE) mRNA, we have developed a reverse
      transcription (RT)-coupled competitive PCR (RT-PCR) assay with a deletion mutant
      internal standard. The RT-PCR detects ACE mRNA from both human and bovine
      sources. ACE mRNA was detected in total RNA from cultured human saphenous vein
      smooth muscle cells (HuSV-SMCs) and from bovine pulmonary artery (BPA) SMCs. BPA
      SMC expressed ninefold less ACE mRNA than BPA endothelial cells, and threefold
      less than HuSV-SMCs. Apparent amounts of ACE mRNA were 118,350 +/- 2,300 copies
      in HuSV-SMCs and 42,200 +/- 11,300 copies in BPA-SMCs per microgram of total cell
      RNA. The accuracy of the absolute values is subject to the limitations of the
      assumptions used to calculate them. These data support the hypothesis that
      components of the renin-angiotensin system are transcribed by SMCs.

PMID- 7580902
TI  - Minimal length requirement of the single-stranded tails for ligation-independent
      cloning (LIC) of PCR products.
AB  - The ligation-independent cloning of PCR products (LIC-PCR) is a versatile and
      highly efficient cloning procedure resulting in recombinant clones only.
      Recombinants are generated between PCR products and a PCR-amplified vector
      through defined complementary single-stranded (ss) ends artificially generated
      with T4 DNA polymerase. This procedure does not require restriction enzymes,
      alkaline phosphatase, or DNA ligase. The primers used for amplification contain
      an additional 12-nucleotide sequence at their 5' ends that is complementary in
      the vector- and insert-specific primers. The (3'-->5') exonuclease activity of T4
      DNA polymerase is used in combination with a predetermined dNTP (dGTP for the
      inserts and dCTP for the vector) to specifically remove 12 nucleotides from each
      3' end of the PCR fragments. Because of the complementarity of the ends that are
      generated, circularization can occur between vector and insert. The recombinant
      molecules do not require in vitro ligation for efficient bacterial
      transformation. To make this technique widely applicable, we have simplified the
      handling of the PCR fragments prior to LIC. The PCR products do not need further
      purification following the T4 DNA polymerase treatment. Incubation of vector and
      insert PCR fragments for as little as 5 min is sufficient for a high yield of
      recombinants. Comparison of the transformation efficiencies using different
      length LIC tails revealed that using 12-nucleotide cohesive ends produced four
      times more transformants than were obtained with the LIC with 10-nucleotide
      cohesive ends. When the LIC tails were 8 nucleotides long, no transformants were
      obtained. PCR fragment purification, T4 DNA polymerase treatment, and LIC is
      complete in < 1 hr.

PMID- 7580903
TI  - An improved method for semiquantification of gene amplification from archival
      material.
AB  - A differential PCR-based assay is presented that increases the accuracy of
      quantification of C-erbB-2 gene-copy number in DNA extracted from archival
      tumors. The C-erbB-2 gene is amplified in a high percentage of human
      adenocarcinomas arising at numerous sites, including breast, lung, and stomach. A
      number of studies have correlated C-erbB-2 with poor prognosis. Gene copy number
      may be relevant in identifying patients with different clinical outcomes. In this
      study a target gene and a single copy reference gene were coamplified in the same
      reaction tube. The level of target gene amplification was reflected by the ratio
      of the two resulting PCR products. Cell lines exhibiting variable copies ranging
      from 1 to > 8 of the C-erbB-2 gene were used as quality controls. This technique
      can reliably show a single copy difference between cell lines and can be used to
      semiquantitatively estimate gene copy number in DNA extracted from archival
      paraffin-embedded samples.

PMID- 7580904
TI  - A comparison of methods for RNA extraction from lymphocytes for RT-PCR.

PMID- 7580905
TI  - Improved heteroduplex detection of single-base substitutions in PCR-amplified
      DNA.

PMID- 7580906
TI  - Wax-embedded PCR reagents.

PMID- 7580907
TI  - Optimization and troubleshooting in PCR.

PMID- 7580908
TI  - Panhandle PCR.

PMID- 7580909
TI  - Genetic subtyping of human immunodeficiency virus using a heteroduplex mobility
      assay.

PMID- 7580910
TI  - Genomic fingerprinting by microsatellite-primed PCR: a critical evaluation.
AB  - Single PCR primers complementary to microsatellite repeats were used to amplify
      genomic DNA samples from various plant species, as well as from human, yeast, and
      Escherichia coli DNA. Most primers generated distinct amplification products,
      resulting in fingerprint-like banding patterns after agarose gel electrophoresis
      and ethidium bromide staining. These fingerprints allowed distinction among
      different plant taxa at an interspecific as well as intraspecific level.
      Unexpectedly, some of the primers produced bands with the E. coli template DNA as
      well. A detailed examination of the influence of PCR conditions, especially the
      annealing temperature, on the quality of banding patterns suggested that the
      majority of bands were generated by mismatch priming in a way similar to random
      amplified polymorphic DNAs (RAPDs).

PMID- 7580911
TI  - Specific amplification by PCR of rearranged genomic variable regions of
      immunoglobulin genes from mouse hybridoma cells.
AB  - We have designed a novel strategy for the isolation of the rearranged genomic
      fragments encoding the L-VH-D-JH and L-V kappa/lambda-J kappa/lambda regions of
      mouse immunoglobulin genes. This strategy is based on the PCR amplification of
      genomic DNA from mouse hybridomas using multiple specific primers chosen in the
      5'-untranslated region and in the intron downstream of the rearranged JH/J
      kappa/lambda sequences. Variable regions with intact coding sequences, including
      full-length leader peptides (L) can be obtained without previous DNA sequencing.
      Our strategy is based on a genomic template that produces fragments that do not
      need to be adapted for recombinant antibody expression, thus facilitating the
      generation of chimeric and isotype-switched immunoglobulins.

PMID- 7580912
TI  - DNA fingerprinting of crude bacterial lysates using degenerate RAPD primers.
AB  - Methods for identifying isolates of various pathogenic bacteria by DNA
      fingerprinting with random primers (RAPD) have been described recently. In these
      methods many primers are screened and the primers that generate the most
      informative DNA pattern are selected. A new strategy that simplifies the primer
      selection process for RAPD fingerprinting has been developed in our laboratory.
      In this approach, one or more degenerate nucleotides is introduced into the core
      RAPD primer sequence at various nucleotide positions. Results show that a single
      degenerate nucleotide in the primer sequence can significantly change the DNA
      profile obtained for the same template. The more removed the degenerate
      nucleotide is from the 3' end of the primer, the less dramatic is its effect on
      banding pattern. This method utilizing degenerate RAPD (D-RAPD) primers was
      tested on clinical isolates of Legionella pneumoniae, and results were confirmed
      with nondegenerate RAPD primers. Results obtained with D-RAPD primers were in
      total agreement with those obtained with nondegenerate RAPD primers. We propose
      that the use of a core RAPD primer sequence with one or more degenerate
      nucleotide(s) at various positions can expedite the generation of unique DNA
      fingerprints individual organisms. A general method for selecting the most useful
      fingerprinting RAPD primers is discussed.

PMID- 7580913
TI  - An efficient and optimized PCR method with high fidelity for site-directed
      mutagenesis.
AB  - We have developed an efficient method for site-directed mutagenesis using two
      subsequential rounds of PCR. In this method, PCR conditions are optimized to
      favor high fidelity of Taq DNA polymerase in the presence of equimolar
      concentrations of MgCI2 and dNTP in the reaction mixture (pH 5.5-6.2). This
      method makes use of a pair of universal primers and the multiple cloning site of
      pUC/M13 vectors. Only one mutagenic primer is required per target site. In the
      second round of PCR, the 3' extension of the wild-type DNA strand is blocked by
      the presence of a segment of nonhomologous sequence at its 3' end, and as a
      consequence, the amplified, full-length DNA fragment is chiefly from the mutant
      strand. Furthermore, because the mutated DNA fragment has flanking restriction
      sites different from those of the wild-type DNA fragment, the wild-type DNA
      fragment is totally excluded in the step involving selective cloning of the
      mutant DNA fragment. This method was successfully used to introduce four,
      nonadjacent mutations in the 5' regulatory region of the cytochrome P450BM-3
      gene. All 20 analyzed clones from these four cases of mutagenesis carried the
      desired mutations, and no undesired mutations were observed. We observed that the
      larger the number of mismatched nucleotide residues in the mutagenic primer, the
      higher the concentration of MgCI2 was necessary for successful PCR amplification.
      Our experimental results indicate that this method offers improvements in
      efficiency, flexibility, and fidelity.

PMID- 7580914
TI  - Multiple fluorescence-based PCR-SSCP analysis with postlabeling.
AB  - Multiple fluorescence-based PCR single-strand conformation polymorphism (MF-PCR
      SSCP) with postlabeling was developed. The target sequence was amplified by PCR
      using unlabeled primers. Free dNTPs were removed from the amplified products by
      ethanol precipitation. The dNTPs at the 3' ends of the amplified DNA fragments
      were exchanged with fluorescent dUTPs or ddNTPs using Klenow fragment of DNA
      polymerase I. The DNA fragments labeled with fluorescent dUTPs or ddNTPs were
      heat denatured and applied to a nondenaturing polyacrylamide gel set on an
      automated DNA sequencer with a gel temperature-controlling system. The image data
      were analyzed by the computer program Genescan 672. By use of MF-PCR-SSCP with
      postlabeling, seven different single base mutations of the human K-ras oncogene
      were detected even under one electrophoresis condition.

PMID- 7580915
TI  - Multiplex PCR of bcr-abl fusion transcripts in Philadelphia positive acute
      lymphoblastic leukemia.
AB  - We describe a multiplex PCR assay for the detection of bcr-abl fusion mRNA in
      Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL). The
      assay provides a quick method for screening p190 (e1:a2) and p210 (b2:a2 or
      b3:a2) bcr-abl mRNAs simultaneously. The assay proves to be highly sensitive with
      detection of as little as one positive bcr-abl-expressing cell in a background of
      10(5) negative bcr-abl cells. Bone marrow and peripheral blood specimens from six
      patients were in total accordance when run by multiplex PCR and by the single
      primer PCR approach. The multiplex bcr-abl assay may prove to be highly useful
      for screening newly diagnosed patients with ALL for the bcr-abl fusion transcript
      and in following the course of disease during therapy.

PMID- 7580918
TI  - Efficient gene synthesis by Klenow assembly/extension-Pfu polymerase
      amplification (KAPPA) of overlapping oligonucleotides.

PMID- 7580917
TI  - Template integrity is essential for PCR amplification of 20- to 30-kb sequences
      from genomic DNA.

PMID- 7580919
TI  - DNA hybridization analysis of PCR products by non-gel sieving capillary
      electrophoresis.

PMID- 7580920
TI  - Rapid quantitative PCR for determination of relative gene expressions in tissue
      specimens.

PMID- 7580916
TI  - Vir typing: a long-PCR typing method for group A streptococci.
AB  - We have developed a new procedure (Vir typing) for typing Streptococcus pyogenes,
      by amplifying the entire 5- to 7-kb variable vir regulon by long PCR. The
      amplified DNA is then cleaved with HaeIII and visualized by ethidium bromide
      fluorescence after agarose gel electrophoresis. A simple procedure for preparing
      DNA of sufficiently high quality from 96 samples was employed simultaneously.
      This DNA was also used to develop a random amplified polymorphic DNA (RAPD)
      procedure. The discriminatory power of the two DNA-based procedures was compared
      with previous methods, M typing, and multilocus enzyme electrophoresis. Both
      procedures were highly discriminatory, but the stoichiometric yield of
      restriction fragments in Vir typing allows unambiguous interpretation of results.

PMID- 7580922
TI  - Amplification of the total coding sequence of the NF1 gene from peripheral blood
      lymphocyte RNA.

PMID- 7580921
TI  - An efficient method for PCR analysis of mitochondrial DNA from paraffin-embedded
      archival heart tissue.

PMID- 7580923
TI  - Rapid and sensitive analysis of mRNA polyadenylation states by PCR.
AB  - A rapid and sensitive technique is described that measures the length of the
      poly(A) tail on a specific mRNA within subnanogram quantities of total cellular
      RNA [the Poly(A) test (PAT)]. In a single-tube reaction, a poly(dT) primer is
      synthesized in situ on the poly(A) tail of mRNAs using oligo(dT) and DNA ligase.
      By modulating the annealing temperature and primer concentrations, a GC-rich
      adapter sequence is targeted to the 5' end of the poly(dT) primer. This ligated
      poly(dT)-anchor is then used to prime reverse transcription of the mRNA, yielding
      a library of PAT cDNAs. The length of a poly(A) tail is determined by PCR
      amplification using the oligo(dT)-anchor primer and a message-specific primer.
      Comparison of PCR products from different samples allows quantitative
      determination of changes in polyadenylation of a given mRNA. This technique
      overcomes many of the pitfalls associated with conventional poly(A) tail length
      assessments and should prove useful in studying a variety of processes relating
      to polyadenylation.

PMID- 7580924
TI  - Identification of 3'-terminal exons from yeast artificial chromosomes.
AB  - We report an extension of 3'-terminal exon trapping technology to the
      identification of transcribed sequences from yeast artificial chromosomes (YACs).
      A 350-kb YAC containing mouse genomic DNA was gel-purified and used as the target
      DNA for the 3'-terminal exon trapping strategy. A novel direct
      ligation/transfection approach was employed to increase the efficiency of
      trapping 3'-terminal exons from recombinant vector-derived chimeric mRNA. The
      resulting RT-PCR product was then used to generate a plasmid library. Randomly
      chosen individual subclones from this library were sequenced, and the results
      indicate that 86% met sequence criteria characteristic of 3'-terminal exons,
      whereas 14% were background from identified sources. PCR mapping efforts suggest
      eight putative last exons present within this YAC, whereas RT-PCR studies
      demonstrate that three reside within valid expressed sequences.

PMID- 7580925
TI  - Quantitative analysis of specific mRNA transcripts using a competitive PCR assay
      with electrochemiluminescent detection.
AB  - Reverse transcriptase-polymerase chain reaction (RT--PCR) has been widely
      utilized for both the qualitative and quantitative assessment of the levels of
      specific mRNA transcripts in living systems. Quantitation of specific transcripts
      has often proved to be problematic because of the difficulty associated with
      relating the PCR-amplified product to the starting cDNA representing the mRNA of
      interest. We have overcome these difficulties and have developed a competitive
      PCR assay employing the property of electrochemiluminescence for the detection of
      PCR products. This assay possesses the dual advantage of being both
      nonradioactive and highly sensitive.

PMID- 7580928
TI  - Generation of DNA-based markers in specific genome regions by two-primer RAPD
      reactions.
AB  - Random amplified polymorphic DNA (RAPD) markers offer quick screening of
      different regions of the genome for genetic polymorphisms. The standard RAPD
      procedure uses a single 10-base-long random oligonucleotide as a primer to
      amplify short stretches of the genome by PCR. We modified the procedure by using
      two primers in each reaction in a Brassica napus mapping project. We found that
      the two-primer RAPD tends to amplify more and smaller fragments than the standard
      RAPD technique. These new bands were always amplified in the two-primer
      reactions, and Southern analysis revealed that they had no homology to the bands
      amplified in single-primer reactions involving the same primers. Furthermore,
      these new markers were not linked to markers amplified with the same primers in
      the standard RAPD reactions, suggesting that they were amplified from different
      genomic regions. The advantage of the two-primer RAPDs is that it allows more
      reactions to be carried out with a limited number of primers to generate more
      markers. Using a single primer, the number of reactions is equal to the number of
      primers (n), which in turn limits the total number of markers. When using two
      primers in all possible combinations, the total number of reactions increases to
      n x (n-1/2). This method could be useful in conjunction with bulked segregant
      analysis to develop high density maps of certain chromosomal regions. We used
      this approach to map a second marker linked to a gene governing low linolenic
      acid concentration in a B. napus F2 population.

PMID- 7580926
TI  - Batched analysis of genotypes.
AB  - Polymorphic microsatellite markers are widely used in molecular analyses. The
      range of allele sizes and the allele frequencies within a population are
      important characteristics of the marker. Their determination previously has
      involved genotyping a large number of individuals. We have developed a technique
      for defining these characteristics by coamplification of many samples in a DNA
      pool. Groups of 32 and 42 DNA samples were genotyped and results were compared
      with those from individual genotype determinations. To improve the accuracy in
      the estimation of allele frequencies, arithmetic removal of stutter bands was
      carried out and the consistency of each marker was characterized. This approach
      was also applied to a group of 94 individuals. All of the work has been done
      using nonradioactive methods. Potential applications of this technique are in
      population genetics, high throughput genotyping, and loss of heterozygosity
      studies.

PMID- 7580927
TI  - A one-step coupled amplification and oligonucleotide ligation procedure for
      multiplex genetic typing.
AB  - A new technique, coupled amplification and oligonucleotide ligation (CAL), has
      been developed that allows for simultaneous multiplex amplification and
      genotyping of DNA. CAL is a biphasic method that combines in one assay DNA
      amplification by PCR with DNA genotyping by the oligonucleotide ligation assay
      (OLA). By virtue of a difference in the melting temperatures of PCR primer-target
      DNA and OLA probe-target DNA hybrids, the method allows preferential
      amplification of DNA during stage I and oligonucleotide ligation during stage II
      of the reaction. In stage I, target DNA is amplified using high-melting primers
      (Tm values between 68 degrees C and 89 degrees C) in a two-step PCR cycle that
      employs a 94 degrees C denaturation step and a 72 degrees C anneal-elongation
      step. In stage II, genotyping of PCR products by competitive oligonucleotide
      ligation with oligonucleotide probes (Tm values between 51 degrees C and 67
      degrees C) located between the PCR primers is accomplished by several cycles of
      denaturation at 94 degrees C followed by anneal-ligation at 55 degrees C.
      Ligation products are fluorochrome-labeled at their 3' ends and analyzed
      electrophoretically on a fluorescent DNA sequencer. The CAL procedure has been
      used successfully to analyze human genomic DNA for cystic fibrosis (CF) alleles.
      Because product detection occurs concurrently with target amplification, the
      technique is rapid, highly sensitive, and specific and requires minimal sample
      processing.

PMID- 7580929
TI  - Nonradioactive multiplex PCR screening strategy for the simultaneous detection of
      multiple low-density lipoprotein receptor gene mutations.
AB  - We have developed a rapid, nonradioactive screening test enabling the
      simultaneous analysis of three low-density lipoprotein receptor (LDLR) gene
      mutations (D154N, D206E, and V408M), which together account for familial
      hypercholesterolemia (FH) in approximately 90% of the South African Afrikaner
      population. The assay is designed so that FH patients, negative for these founder
      related mutations (found in descendants of European settlers), subsequently can
      be screened for unknown mutations in the mutation-rich exon 4 of the LDLR gene.
      Our screening assay consists of two steps: (1) multiplex allele-specific PCR
      amplification of exons 4 and 9, and (2) simultaneous analysis of single- and
      double-strand conformational polymorphisms in exon 4 by vertical electrophoresis
      on low cross-linked polyacrylamide gels. The simplicity, specificity, and
      versatility of the multiplex assay makes it an ideal system for routine screening
      of FH mutations in large population samples.

PMID- 7580930
TI  - Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe
      system useful for detecting PCR product and nucleic acid hybridization.
AB  - The 5' nuclease PCR assay detects the accumulation of specific PCR product by
      hybridization and cleavage of a double-labeled fluorogenic probe during the
      amplification reaction. The probe is an oligonucleotide with both a reporter
      fluorescent dye and a quencher dye attached. An increase in reporter fluorescence
      intensity indicates that the probe has hybridized to the target PCR product and
      has been cleaved by the 5'-->3' nucleolytic activity of Taq DNA polymerase. In
      this study, probes with the quencher dye attached to an internal nucleotide were
      compared with probes with the quencher dye attached to the 3'-end nucleotide. In
      all cases, the reporter dye was attached to the 5' end. All intact probes showed
      quenching of the reporter fluorescence. In general, probes with the quencher dye
      attached to the 3'-end nucleotide exhibited a larger signal in the 5' nuclease
      PCR assay than the internally labeled probes. It is proposed that the larger
      signal is caused by increased likelihood of cleavage by Taq DNA polymerase when
      the probe is hybridized to a template strand during PCR. Probes with the quencher
      dye attached to the 3'-end nucleotide also exhibited an increase in reporter
      fluorescence intensity when hybridized to a complementary strand. Thus,
      oligonucleotides with reporter and quencher dyes attached at opposite ends can be
      used as homogeneous hybridization probes.

PMID- 7580931
TI  - Development of competitive PCR and the QPCR system 5000 as a transcription-based
      screen.
AB  - We describe the use of the quantitative PCR (QPCR) system 5000 (Perkin-Elmer) and
      competitive PCR in a simple and reproducible assay format for use in establishing
      a screen for the discovery of compounds that affect gene regulation. Insulin-like
      growth factor 1 (IGF-1) mRNA was chosen as an initial target to test the
      sensitivity and reproducibility of the QPCR System 5000 in the quantitation of
      PCR products generated in competitive PCR reactions. We found that with the use
      of sequence-specific probes, the QPCR 5000 could be used easily to distinguish
      between internal standard (IS) and wild-type products in PCR reactions. We were
      able to detect as little as twofold changes in cDNA amounts by using dilutions of
      total rat liver cDNA as a source of IGF-1 message. The QPCR system 5000 could be
      used to analyze 24 competitive PCR reactions (48 samples), single determinations,
      in approximately 1 hr. The flexibility, automation, and sensitivity of the QPCR
      System 5000 makes it a useful tool to measure the transcriptional regulation of
      various mRNAs.

PMID- 7580932
TI  - A simple "universal" DNA extraction procedure using SDS and proteinase K is
      compatible with direct PCR amplification.

PMID- 7580933
TI  - A method for rapid generation of competitive standard molecules for RT-PCR
      avoiding the problem of competitor/probe cross-reactions.

PMID- 7580934
TI  - Single-tube nested PCR with room-temperature-stable reagents.

PMID- 7580935
TI  - Rapid method for separation of microsatellite alleles by the PhastSystem.

PMID- 7580936
TI  - Characterization of growth hormone-induced tyrosine-phosphorylated proteins in
      mouse cells that express GH receptors.
AB  - Following the growth hormone (GH) and GH receptor (R) interaction, the receptor
      and Janus tyrosine kinase 2 (JAK2) become tyrosine phosphorylated along with
      other intracellular proteins. Previously, we reported that GH induces tyrosine
      phosphorylation of intracellular proteins with molecular masses of approx 95 kDa
      (pp95) in mouse 3T3-F442A preadipocytes and in mouse L-cells that express
      recombinant GHRs. We have studied this GH-induced phosphorylation event in
      greater detail. Three proteins with apparent molecular masses of 93, 95, and 96
      kDa showed increased tyrosine phosphorylation in a time-dependent manner
      following GH treatment of cells that express GH receptors. GH-induced tyrosine
      phosphorylation of these proteins is independent of activation of protein kinase
      C (PKC). Cell fractionation studies revealed that the majority of tyrosine
      phosphorylated pp95/96 is located in the cytoplasm. pp95 and pp96 have pIs of
      approx 6.2. Immunoprecipitation and Western blot analyses revealed that pp93 and
      pp95/96 are not immunologically related with Stat1, Stat3, Stat4, JAK2, and GHR.
      Thus, pp93 and pp95/96 may be important GH signal transducers independent of PKC
      activation and different from the characterized members in the JAK-STAT pathway.

PMID- 7580937
TI  - Synthetic peptides derived from the steroid binding domain block modulator and
      molybdate action toward the rat glucocorticoid receptor.
AB  - Modulators are endogenous low-mol-wt inhibitors of glucocorticoid receptor
      activation, and are mimicked by exogenous sodium molybdate. Activation involves
      the dissociation of the 90-kDa heat-shock protein from the receptor. The heat
      shock protein is thought to bind to a conserved 20-amino-acid region in the
      steroid-binding domain of the receptor (595-614 of the rat protein). Synthetic
      peptides corresponding to this amino acid sequence prevented the modulators and
      sodium molybdate from inhibiting receptor activation. These results imply that
      the region 595-614 of the rat glucocorticoid receptor is also a
      modulator/molybdate binding site.

PMID- 7580938
TI  - Modulation of angiotensin II receptor (AT2) mRNA levels in R3T3 cells.
AB  - R3T3 cells, a mouse fibroblast cell line, express the type 2 angiotensin II
      receptor (AT2), but not the AT1 subtype. We previously reported that expression
      of AT2 sites in these cells were regulated by various conditions: 1. The number
      of AT2 sites increased considerably when cells were contact-inhibited; 2.
      Stimulation of R3T3 cells with various mitogens caused a rapid decline of AT2
      binding sites; and 3. Stimulation of cells with angiotensin ligands resulted in
      upregulation of the AT2 sites. In this study, to determine if altered AT2
      expression is under transcriptional, posttranscriptional, or translational
      control, we examined the level of AT2 mRNA in R3T3 cells in response to various
      treatments. There was a 200-fold increase in AT2 mRNA levels in quiescent cells
      as compared to growing cells. Results from nuclear run-on assays suggested that
      the differences in AT2 mRNA levels were primarily caused by changes in the rate
      of AT2 gene transcription. Stimulation of cells with fibroblast growth factor
      caused an approximate threefold reduction of AT2 mRNA levels, and also increased
      the rate of degradation of AT2 mRNA, which correlated with the decrease in AT2
      binding activity seen under these conditions. However, whereas treatment with
      angiotensin ligands increased AT2 binding activity, the level of AT2 transcripts
      did not increase. This pattern of expression implies that regulation of AT2
      receptors occurs at multiple levels, involving translational and/or
      posttranslational as well as transcriptional control, and further affords the
      cell the ability to rapidly modulate the number of AT2 binding sites in response
      to changing extracellular conditions.

PMID- 7580939
TI  - Growth hormone (GH)-induced tyrosine-phosphorylated proteins in cells that
      express GH receptors.
AB  - We have shown previously that growth hormone (GH)-induced tyrosine
      phosphorylation of a 95-kDa protein in mouse L-cells stably transfected with the
      GH receptor. In addition to induction of pp95, we have established that GH also
      induces tyrosine phosphorylation of a 42-kDa protein and a 130-kDa protein, as
      detected with phosphotyrosine antibodies. A time course of tyrosine
      phosphorylation on GH treatment indicates that within the GH signal transduction
      cascade, tyrosine phosphorylation of pp95 occurs by 1 min, whereas tyrosine
      phosphorylation of pp42 was not detected until 5 min. Additionally, the
      concentration of GH needed to stimulate tyrosine phosphorylation of pp42 was
      greater than that required for pp95. The pp42 protein comigrates with a 42-kDa
      protein identified as extracellular signal-regulated kinase 2 (ERK2). Growth
      factors, such as FGF, PDGF, IGF-I, and insulin, induce tyrosine phosphorylation
      of pp42 in pGHR-W10 cells and in 3T3-F442A preadipocytes; however, they are
      unable to induce pp95. These results suggest that GH induction of tyrosine
      phosphorylated pp42 may represent a common signal transduction point of various
      growth factors, including GH, whereas tyrosine phosphorylation of pp95 is GH
      specific.

PMID- 7580940
TI  - Glucocorticoid responsiveness conferred by a cloned DNA binding protein.
AB  - Glucocorticoids stimulate surfactant protein-B (SP-B) (expression in type II
      alveolar cells) by unknown mechanisms. We identified, cloned, and characterized a
      protein that binds the SP-B promoter. This protein, D, increases the activity of
      the SP-B promoter in response to glucocorticoid stimulation. Protein D was
      identified by its ability to bind the SP-B promoter region, which it binds at an
      NF1 site from -184 to -198 bp. Its binding was abolished by digestion of promoter
      DNA with BalI, which cuts at -194. Protein D was cloned and sequenced. It is a
      new DNA binding protein of 33 kDa whose carboxyl end contains a modified basic
      leucine zipper-like DNA binding motif (bzip). The effects of D on SP-B promoter
      activity were studied in H441 cells, using a reporter construct containing 212 bp
      from the SP-B promoter with a luciferase reporter gene (p2121uc), which was
      cotransfected with a protein D expression construct in which D expression was
      controlled by the SV40 early promoter. These two plasmids were cotransfected into
      H441 cells. Without added glucocorticoids, D did not alter SP-B promoter
      activity. When dexamethasone was added, D strongly enhanced SP-B promoter
      activity. Identification of this protein suggests that, at least for SP-B,
      glucocorticoid responsiveness may involve one or more hitherto unknown gene
      activators.

PMID- 7580941
TI  - Expanding the horizons of nursing research.

PMID- 7580942
TI  - Life in a nursing home for the frail elderly: daily routines.
AB  - This study forms part of a research project intended to shape the care of elderly
      residents in two nursing homes so that it better corresponds to their needs. The
      goal of this effort was to look at the life and treatment experiences of frail
      elderly residents. The data were collected by interviewing 31 residents and
      analyzed using continuous comparison methods. The results showed that the nursing
      staff was clearly preoccupied with daily activities, whereas the lives of elderly
      residents received less attention. There was a widespread feeling among residents
      that staff members were always pressed for time and did not want to talk with
      them. Nursing staff should encourage elderly patients to talk about their hopes,
      desires, and everyday thoughts. A closer familiarity with their patients' life
      stories will also help the nursing staff to understand and appreciate the hopes
      of their clients.

PMID- 7580943
TI  - Well-being of caregivers of spouses with Parkinson's disease.
AB  - This study examined the relationship among stages of Parkinson's disease (PD),
      elderly care receivers' physical and social functioning, and spousal caregivers'
      physical, social, psychological, and economic well-being. The nonrandom,
      convenience study sample comprised 30 spousal caregivers of elderly individuals
      diagnosed with PD; all attended group support sessions. Findings indicated a
      statistically significant linear relationship between stages of PD and care
      receivers' functional ability and between care receivers' functional and social
      ability and caregivers' hours of caregiving. Caregivers' health was associated
      with diminished physical functioning of care receivers. Caregivers' age, years of
      marriage, and educational level were associated with their social, psychological,
      and financial well-being. The main implication for nursing practice is that
      elderly family caregivers must be included in mutually developed care plans; they
      are at high risk for diminished well-being because of the time and energy
      involved in providing needed care.

PMID- 7580944
TI  - Religiosity as a dimension of well-being: a challenge for professional nursing.
AB  - The principles of holistic nursing require understanding the human individual as
      a complex and coherent entity consisting of physical, psychic, social, and
      spiritual dimensions. Considering the research evidence about people's
      experiences of well-being, the spiritual dimension, here regarded as synonymous
      with religiosity, does not seem to receive due attention in nursing. This article
      describes the appearance of religiosity as an integral part of people's
      experiences of well-being. Data from interviews with 40 adults who had contacted
      the primary health care system were analyzed on the basis of a qualitative,
      thematic analysis. Christians who belonged to the Evangelical Lutheran Church of
      Finland incorporated their religious values into their experiences of well-being.
      These values were reflected in ideas of the good life, in solutions to everyday
      problems, and in self-care. The results highlight the importance of a nursing
      concept that recognizes each patient's individual well-being.

PMID- 7580945
TI  - Patient factors and central line infection.
AB  - The purpose of this prospective study was to examine the relationship between
      patient-related factors and the development of central venous catheter infection.
      Fifty-three patients, representing 64 central lines, were followed from catheter
      insertion to removal. Information about the patient's age, sex, immunocompetence
      status, central line characteristics, medication regimen, and laboratory results
      was obtained. Results showed that, of these factors, only the medication regimen
      was a promising predictor of infection status. Patients who were receiving
      antibiotics during central line catheterization were at less risk of developing
      infection than patients who were not receiving them.

PMID- 7580946
TI  - Content analysis of nonprofessional caregiver-patient interactions in long-term
      care facilities.
AB  - A content analysis of tape-recorded, nonprofessional caregiver-patient
      interactions was undertaken to determine the nature and content of conversation
      during the provision of morning care in long-term care facilities. Caregivers
      initiated and directed the majority of topics, generally keeping the patient as
      the focus of the interaction. Patients and caregivers initiated different types
      of topics, with caregivers being more interested in care activities, social
      conversation, care environment, and patients' physical health. Patients
      introduced topics of a more personal nature: social systems, reminiscences, and
      hopes and plans. It was concluded that nonprofessional caregivers require
      communication skills training. Questions were raised about the effects of
      caregiver communication on patients in long-term care facilities.

PMID- 7580947
TI  - Focus groups: nursing staff's experiences using restraints.
AB  - A phenomenological approach was used to examine nursing staff's experiences using
      physical restraints. A total of 12 nurses from a tertiary hospital participated
      in one of three focus groups. Exploring the attitudes of nurses can contribute to
      a better understanding of how decisions are made concerning restraints. An
      analysis of the focus group data resulted in a description of the lived
      experiences of nurses using restraints. Seven themes emerged from the data, one
      of which reflected that the nurses felt ambiguous about restraints, yet they made
      judgments and justified their decisions after assessing patient characteristics,
      environmental safety, and unit traditions. Nurse clinicians could use the focus
      group method to sensitize themselves to the staff's needs and to allow staff the
      opportunity to share ideas and to dispel misconceptions about restraints.

PMID- 7580948
TI  - Predictors of Taiwanese nurses' intention to care for patients who are HIV
      positive.
AB  - The purpose of this research was to explore the knowledge of, attitudes toward,
      and intention to care for HIV-positive patients among 223 Taiwanese nurses. They
      worked in many different settings and had a variety of levels of exposure to HIV
      positive patients. The findings of this research revealed that most Taiwanese
      nurses lacked sufficient knowledge to prevent themselves from becoming infected
      in the workplace. Their attitude about giving care to HIV-positive patients was
      generally negative; most nurses stated that they did not intend to care for these
      patients. A regression analysis revealed that knowledge was not a significant
      predictor of intention. Attitudes about societal treatment of HIV-positive people
      and nursing care were significant predictors of intention. Implications for
      practice and education of Taiwanese nurses are discussed.

PMID- 7580949
TI  - Boomerang pillows and respiratory capacity in frail elderly women.
AB  - An exploratory study was done to determine whether frail elderly women placed on
      boomerang pillows would have an altered minute volume after 10 minutes. A
      convenience sample of 18 subjects took part in the study. A repeated measures
      design was used in which subjects served as their own controls. After 10 minutes
      on the boomerang pillows, there was a significant reduction in the minute volume
      of subjects. Boomerang pillows may be contraindicated in people with reduced lung
      capacity due to age; however, further research on a larger sample of frail
      elderly women is indicated.

PMID- 7580950
TI  - The social HMOs. Meeting the challenge of integrated team care coordination.
AB  - Four social health maintenance organizations (social HMOs) implemented care
      coordination programs in 1985 to integrate acute and long-term care for aged
      Medicare beneficiaries. The team approach to care coordination has been the key
      concept of the model at all four sites. Team members include the primary care
      physician, the care coordinator, inpatient and medical office staff, geriatric
      nurse practitioners, home care nurses and social workers, contracted community
      based care staff, and, at three of the sites, volunteers. This article describes
      how care coordinators work with the health care teams in the social HMOs.

PMID- 7580951
TI  - Service coordinators in senior housing. An exploration of an emerging role in
      long-term care.
AB  - The evolving role of service coordinators in federally subsidized senior housing
      offers a new opportunity to enhance service delivery to older adults who are
      aging in place. Senior housing occupies an unrecognized but important niche in
      the long-term care continuum. The Department of Housing and Urban Development has
      acknowledged the need for housing-based social services by developing and funding
      service coordinator positions. Efforts by visionary agencies have demonstrated
      that an on-site social service professional improves access to needed supportive
      services and assists housing staff to understand age-related issues. Although the
      need and efficacy of housing-based services have been substantiated, the day-to
      day practice has not been widely examined. This article offers a description of
      the unique dynamics of providing social services in a housing setting, based on
      the experiences of service coordinators in the San Francisco Bay area.

PMID- 7580953
TI  - Priority setting in case management based on need and risk.
AB  - The Long-Term Care Program of the Capital Regional District, Victoria, British
      Columbia, experienced increasing demands for service and corresponding pressures
      on community case managers. A priority setting tool was developed and implemented
      as a means of prioritizing new intakes. This tool represents a shift toward a
      broader scope of practice in which both client need and risk are measured.
      Priorities based on these scores have streamlined current case management
      practice and helped to ensure that newly referred individuals are seen in a
      consistent and timely manner.

PMID- 7580952
TI  - The evolution of case management.

PMID- 7580954
TI  - State-of-the-art education for case management in long-term care.
AB  - In 1991, the School of Nursing at San Francisco State University initiated a
      master's degree program in case management/long-term care. It was one of the
      first programs in the country to take a broad view of long-term care to include
      client populations from infancy through old age and to prepare nurses at the
      graduate level in the case management role. This article describes the methods
      for developing the program, identifies major areas of professional competence in
      case management, describes the program and major teaching approaches, and
      presents preliminary evaluation findings. The experience at San Francisco State
      may provide other nursing faculty, staff educators, and case management trainers
      with helpful information for developing educational programs and continuing
      education courses in case management.

PMID- 7580955
TI  - Case manager attitudes toward client-directed care.
AB  - Advocates for individuals with severe and long-term physical disabilities have
      lobbied aggressively in the U.S. and Canada for the implementation of Independent
      Provider Care (IPC). In this model of home support service delivery, the client
      assumes sole responsibility for the management and scheduling of his or her
      personal care and home support. This article reports on the findings of a
      Canadian survey that assessed case managers' beliefs regarding the efficacy,
      benefits, and risks to clients of an IPC program. Survey results indicated that
      case managers generally believed that IPC would not significantly improve their
      clients' well-being and quality of care, would pose risks of abuse to both the
      client and support attendant, and would result in greater job demands for case
      managers. Possible sources of their apprehension are identified, and measures
      that may help to alleviate their concerns are discussed.

PMID- 7580956
TI  - [Activity of cytochrome P-450 and structural status of the murine brain
      microsomal membrane upon multiple exposures to hyperbaric conditions].

PMID- 7580957
TI  - [Evaporative water loss by small cetaceans].

PMID- 7580958
TI  - [Use of an immunotoxin against the human T-lymphocyte CD5 antigen for removing
      "passenger" lymphocytes from kidney transplants].

PMID- 7580959
TI  - [A spatial structure model of the basic antigenic determinant of the human
      immunodeficiency virus type 1 gp120 protein].

PMID- 7580960
TI  - [Oxidative stability of Na,K-ATPase].

PMID- 7580961
TI  - [New methods of immunoenzyme analysis, based on the use of interpolyelectrolyte
      reactions].

PMID- 7580962
TI  - [Structure-activity changes of mitochondria from cultured cells upon disruption
      of energy metabolism].

PMID- 7580964
TI  - [Three types of monkey striatal neuron impulse activity connected with behavioral
      changes].

PMID- 7580963
TI  - [Molecular heterogeneity of alpha-glycerophosphate dehydrogenase in vertebrate
      tissues].

PMID- 7580966
TI  - [Dolphin anal glands].

PMID- 7580965
TI  - [A perfluorocarbon emulsion inhibits neutrophil activation].

PMID- 7580968
TI  - [Coupling of disaccharide hydrolysis with absorption of formed glucose in the
      small intestine in vivo].

PMID- 7580967
TI  - [The effect of amiloride and furosemide on synaptic potentials in spinal motor
      neurons and difference in potentials in frog dermal epithelium].

PMID- 7580969
TI  - [The possible role of dopamine beta-monooxygenase in the pathogenesis of
      schizophrenia].

PMID- 7580970
TI  - [Modification of immune response by implanting a suspension and antigen
      stimulated lymphoid organs in an allogeneic system].

PMID- 7580972
TI  - [Genetic polymorphism of a human gene locus containing the tumor necrosis factor
      gene: new markers of susceptibility to multiple sclerosis].

PMID- 7580971
TI  - [Thermostable alanine racemase from Escherichia coli strain XL1-Blue with cloned
      pBLUESCRIPT ("Stratagene")].

PMID- 7580973
TI  - [Neutralizing activity of C-reactive protein in relation to pore-forming
      bacterial cytotoxins].

PMID- 7580974
TI  - [Hypoxic training stimulates new growth of pancreatic beta cells and slows
      development of diabetes mellitus in rats].

PMID- 7580975
TI  - [Distribution of Canidae Bsp-repeat transcripts in arctic fox kidney: structural
      similarity of Bsp-repeats with SI NEs].

PMID- 7580976
TI  - [Binding characteristics of a specific blocker (3H)-quinuclidinylbenzilate to M
      cholinergic receptors from rat cerebral cortex membranes].

PMID- 7580977
TI  - [Features of murine embryogenesis during exposure to serotonin before or after
      irradiating the zygote in the period prior to nervous system development].

PMID- 7580978
TI  - [Genetic control of steroidogenesis in laboratory mice Leydig cells].

PMID- 7580979
TI  - [The transport function of GroEL family chaperonins].

PMID- 7580980
TI  - [Cytotoxic activity of murine peritoneal cavity cells during inflammation in
      vivo].

PMID- 7580981
TI  - [Lens induction in the gastrula ectoderm under the effect of adult frog lens
      epithelium].

PMID- 7580982
TI  - [Changes in erythrocytes in the rat cerebral circulation in long-term cerebral
      ischemia].

PMID- 7580983
TI  - [The effect of solvents on the activity of new morphinan series analgesics].

PMID- 7580984
TI  - [Seasonal changes in the activity rhythm of the beaver, Castor fiber].

PMID- 7580986
TI  - [Melatonin and epithalamin inhibit the process of free radical oxidation in
      rats].

PMID- 7580985
TI  - [Effect of chemical desympathization on afferent neurocytes and the neuromuscular
      synapse].

PMID- 7580987
TI  - [Restoration and intensification of cold rabbit skin thermoreceptor pulsation
      using EDTA on cold skin].

PMID- 7580988
TI  - [Long-term potentiation in the helix central nervous system after intracellular
      tetanization].

PMID- 7580989
TI  - [Allele-specific sequencing].

PMID- 7580990
TI  - [Effect of L-glutamate on the structure of the molecular lyer of frog cerebellum
      in vitro].

PMID- 7580991
TI  - [A protein product of the tobamovirus open translation frame forms a stable
      complex with translation elongation factor eEF-1alpha].

PMID- 7580992
TI  - [Change in the Bacillus thuringiensis subsp. Israelensis plasmid DNA spectrum
      during growth dynamics].

PMID- 7580993
TI  - [Functional activity of monoclonal antibodies against the CDw50 antigen (ICAM
      3)].

PMID- 7580994
TI  - [Mechanism for determining the number of exchanges in a pair of homologous
      chromosomes].

PMID- 7580995
TI  - Approaches that mitigate doxorubicin-induced delayed adverse effects on
      mitochondrial function in rat hearts; liposome-encapsulated doxorubicin or
      combination therapy with antioxidant.
AB  - This experiment was designed to evaluate whether or not liposomal encapsulated
      doxorubicin and combination therapy of free doxorubicin with coenzyme Q10, an
      antioxidant, mitigate the delayed adverse effects on cardiac muscle mitochondria.
      Rats aged 7 weeks were divided into the following four groups; rats were injected
      with doxorubicin or liposomal encapsulated-doxorubicin, total dose 15 mg/kg. The
      doxorubicin group consisted of two subgroups depending on diet, i.e., standard
      diet or 0.2% coenzyme Q10 diet. Mitochondria from cardiac muscles were prepared
      from rats aged 13 and 35 weeks. No significant decrease in the activity of
      complex I of the mitochondrial electron transport chain was observed in rats aged
      13 weeks among the groups, however, significant decreases in the activity in rats
      aged 35 weeks were observed in the doxorubicin and liposomal doxorubicin groups
      compared with the corresponding control rats. In contrast, no significant change
      in complex I activity was observed in rats fed with coenzyme Q10 diet
      irrespective of doxorubicin treatment. From these results, not liposomal
      encapsulation of doxorubicin but combination therapy with antioxidant might be
      expected to reduce the delayed adverse effects of doxorubicin on heart
      mitochondria.

PMID- 7580997
TI  - Thermodynamic aspects of the thermal stability of human serum albumin.
AB  - The thermal denaturation of human serum albumin can be described by a two step
      process according to the model of Eyring and Lumry (N <==> U --> I). It was found
      that the rate of irreversible process (U-->I) is very slow, allowing its
      resolution as a reversible one on the basis of two state approximation (N <==>
      U). The delta H degrees of denaturation was 88.9 degrees Kcal/mol. This suggests
      that in the unfolding state, the protein partially possesses its tertiary
      structure. The melting temperature of the protein obtained by differential
      scanning calorimetry was of 63.14 degrees C, this value was in agreement with
      those obtained by other techniques such as fluorescence and enzymatic activity of
      the protein.

PMID- 7580996
TI  - Substance P stimulates the loss of cell-associated high molecular weight
      glycoconjugates from cultured hamster tracheal epithelial cells through
      polymorphonuclear leucocytes activation.
AB  - Abnormal and excessive mucus secretion is a characteristic feature of many
      chronic inflammatory lung diseases accompanied by the influx of polymorphonuclear
      leucocytes (PMNs) into the airway and the release of substance P from the
      peripheral endings of primary sensory neurons. We examined whether PMNs activated
      by substance P (10 microM) can affect the secretion of high-molecular-weight
      glycoconjugates (HMWG), which is used as a marker of mucus, from cultured hamster
      tracheal epithelial cells. We measured both the released and the cell-associated
      HMWG. Substance P-activated PMNs (10(6) cells/ml) reduced the amount of cell
      associated HMWG to 76% of the control level, but did not affect the amount of the
      released HMWG. The reduction of the amount of cell-associated HMWG was inhibited
      by ONO-5046, a specific elastase inhibitor. In addition, the HMWG was digested by
      the activated PMNs. These findings suggested that substance P stimulates the loss
      of the cell-associated HMWG and degrades the released HMWG from cultured hamster
      tracheal epithelial cells through PMNs activation.

PMID- 7580999
TI  - The accessibility of thiophosphorylated groups in DNA fragments to the enzymatic
      activity of ligases and restriction endonuclease Bbs I.
AB  - The aim of this paper was to test the possibility to ligate and hydrolyse DNA
      sequences containing thiomodified ends and bonds. T4 DNA ligase was shown to
      ligate DNA fragments regardless of whether it contains phosphorylated or
      thiophosphorylated 5'-end. But the cleavage of an internally thiomodified
      phosphodiester bond was found to be totally inhibited when using the non
      palindromic restrictase Bbs I. The special properties of this restriction
      endonuclease should allow the development of an oriented cloning strategy when
      combined with T4 ligase and a thiophosphorylation of DNA fragments.

PMID- 7580998
TI  - Insertion mutagenesis of Chlamydomonas reinhardtii by electroporation and
      heterologous DNA.
AB  - We introduced plasmid pCmVCAT containing a chloramphenicol acetyltransferase
      (CAT) gene, flanked by the cauliflower mosaic virus 35S promoter and nopaline
      synthase polyadenylation sequences, into Chlamydomonas reinhardtii by
      electroporation; chloramphenicol (CAM) resistance was used for selection. Several
      mutants with aberrant response to cadmium (Cd) toxicity were obtained by
      screening CAM resistant transformants. Southern blot analysis showed random
      integration of pCmVCAT sequence into the nuclear genome. Expression of CAT gene
      was confirmed by the detection of CAT gene transcript in Northern blot analysis
      and the detection of CAT enzyme by ELISA assay. This study demonstrated the
      feasibility of transforming Chlamydomonas reinhardtii with heterologous DNA by
      electroporation, and the expression of heterologous gene, in this alga.

PMID- 7581000
TI  - The pathophysiological roles of heterogeneous eosinophils in allergic rhinitis
      caused by house dust mites.
AB  - We examined the biological characteristics of normodense and hypodense
      eosinophils prepared from the peripheral blood of the patients with allergic
      rhinitis caused by house dust mites by measuring leukotriene C4 (LTC4), platelet
      activating factor (PAF), and superoxide anions. The normodense (density: 1.100
      1.095) and the hypodense (density: 1.080-1.070) eosinophils were prepared by a
      Percoll density gradient. The normodense eosinophils produced a greater amount of
      LTC4 (15 ng/10(6) cells) after stimulation by calcium ionophore A23187 than the
      hypodense eosinophils (1.8 ng/10(6) cells). On the other hand, in the hypodense
      eosinophils higher amounts of both PAF (5210 pg/10(7) cells/15 min) and
      superoxide anions (0.33 nmoles/10(7) cells/min) were produced by calcium
      ionophore A23187 than in the normodense eosinophils, 501 pg/10(7) cells/15 min
      and 0.18 nmoles/10(7) cells/min, respectively. Considering these results, it is
      suggested that the two eosinophil subpopulations have distinct biological roles
      in generating these inflammatory mediators which appear as typical pathological
      features of allergic rhinitis.

PMID- 7581001
TI  - Anion effects on vesicle acidification in Dictyostelium.
AB  - Chloride ions stimulated the ATP-dependent formation of a proton gradient in
      vesicles derived from amoebae of the cellular slime mould, D. discoideum, and
      reduced the formation of a membrane potential, inhibited rather than stimulated
      the formation of the proton gradient. Since bicarbonate ions did not inhibit H(+)
      ATPase activity we conclude that they enter the vesicles and combine with
      translocated protons. This finding is consistent with the suggestion that the
      membranes of the light vesicle fraction are fragments of contractile vacuole
      complexes, and that these organelles increase their osmotic activity by taking up
      bicarbonate ions and protons from the cytoplasm, and then release water and
      carbonic acid into the extracellular milieu.

PMID- 7581002
TI  - Effect of chloride on the binding kinetics of various stilbenedisulfonates to
      band 3.
AB  - To determine the mechanism of apparent competitive binding of chloride and
      stilbenedisulfonates ( S ) to band 3 ( B ), we have compared the binding kinetics
      of three stilbenedisulfonates [ DIDS, 4,4'-diisothiocyanato-2, 2'
      stilbenedisulfonate; H2DIDS 4,4'-diisothiocyanodihydro-2, 2'-stilbenedisulfonate
      and DBDS, 4,4'-dibenzamido-2, 2'-stilbenedisulfonate ] in the absence and
      presence of 150 mM sodium chloride at constant ionic strength. Biphasic time
      courses were observed with the fast phase rate constants following second-order
      kinetics, and the slow phase rate constants following saturation kinetics
      according to the mechanism: [formula: see text] The results can be understood in
      terms of the effect of chloride on each of these reaction steps. Chloride
      increased k1 by about 2-fold, but decreased k-1 8-fold for H2DIDS. Thus, 150 mM
      chloride increased the initial affinity of H2DIDS by about 19-fold. There was a 3
      fold increase in the initial affinity for DIDS, but little or no effect of
      chloride on the initial affinity of DBDS. There was no effect of chloride on k2,
      but, previous "off" rate measurements showed that 150 mM chloride increases k-2
      about 16-fold for DBDS and about 12-fold for H2DIDS. Taken together, these
      results indicate that chloride allosterically competes with stilbenedisulfonates
      for binding to band 3, predominantly by substantially shifting the second
      isomerization equilibrium to the left.

PMID- 7581003
TI  - Recombinant A17 Lys human insulin: purification and characterization.
AB  - Recombinant A17 Lys human insulin precursor expressed in yeast cells was isolated
      from the culture medium. After purification, the precursor was converted into A17
      Lys human insulin. A17 Lys human insulin can be crystallized but has much lower
      receptor-binding and biological activities than porcine or human insulin where
      A17 is Glu. It is proposed that the A17 Glu residue may be involved in the
      receptor-binding or the active site of human insulin.

PMID- 7581004
TI  - A novel glutamate dehydrogenase from bovine brain: purification and
      characterization.
AB  - A soluble form of novel glutamate dehydrogenase has been purified from bovine
      brain. The preparation was homogeneous on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and composed of six identical subunits having a subunit size
      of 57,500 Da. The biochemical properties of glutamate dehydrogenase such as N
      terminal amino acids sequences, kinetic parameters, amino acids analysis, and
      optimum pH were examined in both reductive amination of alpha-ketoglutarate and
      oxidative deamination of glutamate. N-terminal amino acid sequences of the bovine
      brain enzyme showed the significant differences in the first 5 amino acids
      compared to other glutamate dehydrogenases from various sources. These results
      indicate that glutamate dehydrogenase isolated from bovine brain is a novel
      polypeptide.

PMID- 7581006
TI  - Protein ligand interactions 7 halogenated pyridinium salts as inhibitors of
      acetylcholinesterase from Electrophorus electricus.
AB  - The interaction of halo-quaternary pyridinium hydrochloride salts on
      acetylcholinesterase (AChE, E.C.3.1.1.7) has been investigated. Kinetic analysis
      has shown that they reflect a non-competitive inhibition with Ki values in the
      range 8-13 microM and 5-34 microM for chloro- and bromo-substituted salts
      respectively. Spectrophotometry was used to study the binding of the ligands with
      the enzyme and Scatchard analysis used to calculate the respective dissociation
      constants (Kd) and the number of binding sites. The substitution position of the
      halogen on the pyridine ring also influenced the binding capacity and the Ki
      values.

PMID- 7581005
TI  - Study of retinoic acid effect upon retinoic acid receptors beta (RAR-beta) in C6
      cultured glioma cells.
AB  - Using monoclonal antibodies against the RAR-alpha and RAR-beta retinoic
      receptors, we demonstrated that these receptors were present together in C6
      glioma cells as two isoforms of 50 and 55 kDa. For RAR-beta, the 50 kDa isoform
      predominated (60 to 80% of the total of the two isoforms). After a treatment for
      48 h with retinoic acid 10 microM, the 55 kDa form was enhanced, while no effect
      was observed either on RAR-alpha isoforms from C6 cells and on both RAR-alpha and
      RAR-beta forms from neuroblastoma SKN SH SY5Y used as a control. Using purified
      neuronal and glial rat brain nuclei, we showed that the 55 kDa isoform from RAR
      beta predominated in glial cells. These results suggest that retinoic acid
      treatment of C6 cells led to a partial differentiation, the enhancement of the
      heavy form of RAR-beta being a marker of this phenomenon.

PMID- 7581007
TI  - Molecular evolution of the multigene family of intracellular lipid-binding
      proteins.
AB  - The intracellular lipid-binding proteins are a group of homologous proteins which
      bind and facilitate the transport of fatty acids, bile acids and retinoids. The
      evolutionary relationship of 51 family members from vertebrates and invertebrates
      was analyzed. The inferred phylogeny implies the occurrence of at least 14 gene
      duplications and contains five regions where the branching order is statistically
      non-significant--this uncertainty explaining most inconsistencies between
      previous phylogenetic analyses. The phylogeny also suggests that the intestinal
      fatty acid-binding protein and the liver fatty acid-binding protein/ileal lipid
      binding protein subfamilies diverged from the other subfamilies before the
      vertebrate-invertebrate split. Finally, results presented herein indicate that
      the putative fatty acid-binding domain of NMDA receptor 1 is unlikely to be a
      member of this family.

PMID- 7581008
TI  - Inhibition of purified chicken gizzard smooth muscle ecto-ATPAse by P2
      purinoceptor antagonists.
AB  - Several "specific" inhibitors of P2 purinergic receptors (purinoceptors) were
      evaluated for their ability to inhibit purified chicken gizzard cell membrane
      ecto-ATPase. The P2 purinoceptor antagonists tested included suramin, triazine
      based reactive textile dyes, and non-specific total protein dyes. All inhibited
      the purified ecto-ATPase, with half maximal inhibition from approximately 20 to
      120 microM. Thin layer chromatography purified Cibacron Blue 3GA, also known as
      Reactive Blue 2, was demonstrated to inhibit immunopure ecto-ATPase with an IC50
      of 44 microM. Thus, for the first time, these compounds used to pharmacologically
      classify the subtypes of P2 purinoceptors are demonstrated to have direct
      inhibitory effects on purified ecto-ATPase. Therefore, data generated using these
      compounds on purinoceptors must be interpreted in light of their direct
      inhibitory effect on the ecto-ATPase found in the same tissues.

PMID- 7581009
TI  - Effect of inhibitors on the transport of dinitrophenyl-S-glutathione in human
      erythrocytes.
AB  - Effect of inhibitors on and pH dependence of the export of dinitrophenyl-S
      glutathione (DNP-SG), a glutathione S-conjugate formed upon in vivo conjugation
      of 1-chloro-2,4-dinitrobenzene to glutathione, was studied in intact human
      erythrocytes. The transport was inhibited by orthovanadate (IC50 = 80 microM) and
      fluoride (IC50 = 9 nM). Erythrocyte anion exchange (Band 3) protein inhibitors
      DIDS and SITS did not exert any significant effect on the transport. The
      transport rate increased with increasing extracellular pH in the range of 6.0
      8.0. The Arrhenius activation energy of the process was 72.4 +/- 1.3 kJ/mol.
      Membrane potential, extracellular sodium/potassium concentration ratio and
      extracellular osmolality in the range 300-600 mOsm did not influence the export
      rate.

PMID- 7581010
TI  - Measurement of phosphotyrosine phosphatase activity using the Folin-Ciocalteu
      phenol reaction.
AB  - An assay for the estimation of phosphotyrosine phosphatase using the Folin
      Ciocalteu phenol reaction to monitor enzyme activity is presented. The method is
      based on the property of the substrate phosphotyrosine not to react as a phenol
      until it is dephosphorylated. The method is sensitive, there is no interference
      from the use of detergents and it does not rely on special laboratory equipment
      to distinguish tyrosine from phosphotyrosine.

PMID- 7581011
TI  - Intracellular Ca2+ pool depletion is linked to the induction of nitric oxide
      synthesis in murine peritoneal macrophages.
AB  - The ability of putative Ca(2+)-ATPase inhibitor of endoplasmic reticulum (ER),
      thapsigargin (TG), to induce nitric oxide (NO) synthesis in murine peritoneal
      macrophages was examined. TG alone had small effect on NO synthesis, whereas TG
      in combination with LPS markedly increased NO synthesis in a dose dependent
      manner. This increase in NO synthesis was reflected as increased amount of
      inducible NO synthase (iNOS) mRNA by Northern blotting. In addition, the ability
      of TG on NO synthesis could be mimicked by another chemically unrelated inhibitor
      of Ca(2+)-ATPase, 2,5-DI-(t-butyl)-1, 4-benzohydroquinone (tBuBHQ). Adding EGTA,
      a calcium chelator, to the incubation medium significantly reduced the ability of
      macrophages to induce NO synthesis in response to the optimal stimulation of TG
      or TG plus LPS. These results therefore demonstrate that intracellular Ca2+ pool
      depletion is linked to the induction of NO synthesis in murine peritoneal
      macrophages and further suggest that it is also related with interferon-gamma
      (IFN-gamma)-induced signaling.

PMID- 7581013
TI  - Serum zinc level : a possible index in the pathogenesis of peptic ulcer syndrome.
AB  - The present investigation shows a possible correlation between serum zinc level
      and peptic ulcer disease/syndrome and a plausible mechanism for the finding.
      Clinicopathological study of patients with peptic ulcer diseases followed by
      confirmed endoscopic findings shows a significant low serum zinc level, 0.846 +/-
      0.15 ug/ ml +/- S.D. (P < 0.001) with an exception of approx. 10% of the
      patients. To understand the cellular mechanism of low zinc levels in serum,
      tissue zinc content of gastric mucosa was determined. A significant increased
      value (P < 0.01) of zinc content in gastric mucosa of patients with peptic ulcer
      diathesis was noted. Carbonic anhydrase, a major zinc containing enzyme was also
      determined in erythrocytes. However, no change of erythrocyte carbonic anhydrase
      content was noted. To assess the nutritional status of the patients in relation
      to the low serum zinc value, serum albumin level was also determined. The low
      serum zinc level of the peptic ulcer patients is possibly due to the positive
      shift for the zinc from serum to the gastric mucosa.

PMID- 7581012
TI  - Immunoreactivity of PKC gammalambda and RACK1 in baker's yeast, lobster and wheat
      germ.
AB  - Varied patterns of immunoreactive bands of protein kinase C gamma (PKC gamma) and
      receptor for activated C-kinase-1 (RACK1) were detected by analysis of Western
      blots in crude extracts of wheat germ, lobster tail meat, and three strains of
      baker's yeast. Anti-PKC lambda also reacted with wheat germ and yeast extracts,
      but failed to react with the lobster extract. The findings may implicate a
      regulatory role and an evolutionary conservation of these PKC isoenzymes and
      their receptor proteins in eukaryotes.

PMID- 7581014
TI  - Rat mitochondrial mtDNA-binding proteins to inter-specifically conserved
      sequences in the displacement loop region of vertebrate mtDNAs.
AB  - We describe two new inter-specifically conserved sequences named Mt5 and Mt6
      elements which are around the termination associated sequence (TAS) at the 3' end
      of the displacement loop (D-loop) region of vertebrate mtDNAs. We employed gel
      mobility shift assay to search for D-loop-binding proteins using partially
      purified rat mitochondrial mtDNA-binding proteins and 10 human DNA fragments
      covering the entire D-loop region as probe DNAs. Competition binding assays
      indicated the presence of four different rat mitochondrial D-loop-binding
      proteins. Each of the rat proteins bound, in a sequence-specific manner, to a
      probe DNA containing an inter-specifically conserved sequence; TAS, Mt5, B block,
      and a A+T-rich sequence overlapping the conserved sequence block I.

PMID- 7581015
TI  - A megadalton protein (Pc2500) is present during the intraerythrocytic development
      of P. chabaudi.
AB  - Red cells infected with Plasmodium chabaudi display a megadalton protein, named
      Pc2500, synthesized during the early trophozoite stage with an apparent molecular
      mass of 2500 kDa. When infected red cells at the young trophozoite stage
      metabolically labeled with [35S] methionine are treated with Triton X-100, the
      megadalton protein remains in the insoluble fraction. At this stage, Pc2500 was
      found to be phosphorylated when infected red cells were incubated with [32P]
      orthophosphate. In late trophozoite stage, the Pc2500 is solubilized in Triton X
      100 and is unphosphorylated. Infected cells, were subjected to nitrogen
      cavitation. Analysis of isolated erythrocyte membranes and parasites using
      electron microscopy and marker enzymes demonstrated the purity of these
      fractions. In the phosphorylated from, Pc2500 was shown to be mostly associated
      with the parasite whereas, at the late trophozoite stage, it was found to have
      migrated to the host cell membrane.

PMID- 7581016
TI  - Characterization of neurotrophic factors produced by immortalized mouse brain
      glial cells (VR-2g).
AB  - We analyzed the neurotrophic factors secreted by immortalized fetal mouse brain
      glial cells (VR-2g). Concentrated conditioned medium of VR-2g cells were applied
      to a gel filtration column and the trophic activities of the fractions were
      determined by the bioassay method with primary fetal rat striatal neurons.
      Several peaks of neurotrophic activity were detected, the most prominent of which
      was found in a fraction of molecular weight 5-7 kDa. In peak fractions of
      molecular weight 13-26 kDa, molecules reactive to anti-NGF antibodies were
      detected by Western blotting only in non-reduced condition of SDS-PAGE. Anti-NGF
      antibodies absorbed 40% of the neurotrophic activities in the conditioned medium
      of VR-2g cells.

PMID- 7581017
TI  - Domoic acid induces neurotoxicity and ip3 mobilization in cultured cells of
      embryonic chick retina.
AB  - Domoic acid (DOM), 1 to 50 microM, a glutamate agonist responsible for several
      neurological effects such as loss of memory and confusion, induced the death of
      cultured neurons of chick embryonic retina, in a concentration- and Ca(2+)
      dependent manner. This effect was blocked by 100 microM CNQX, a competitive
      antagonist of the non-NMDA receptor, but not by 10 microM MK-801, a non
      competitive antagonist of the NMDA receptor. DOM also induced inositol
      triphosphate (ip3) accumulation 4 to 7 times above basal levels. This effect was
      also dependent on external Ca2+ and was entirely blocked by 100 microM CNQX, but
      not by 10 microM MK-801. These results suggest that DOM interaction with non-NMDA
      glutamate receptors mediates signal transduction with ip3 accumulation and cell
      death.

PMID- 7581018
TI  - The effect of parturition on the interactions within pairs of common marmosets
      (Callithrix jacchus).
AB  - The relationship within common marmoset (Callithrix jacchus) pairs is based on
      pair-bond formation. This pair-bond is important for the successful rearing of
      the young and for the enhancement of reproductive success. Female marmosets bear
      twins which are carried mainly by males starting on the first day after the birth
      of the infants. Little is known, however, about the patterns of sociosexual
      interaction between callitrichid pairs and how these interactions change after
      the arrival of offspring. To evaluate the effect of parturition on these
      interactions, three heterosexual pairs of common marmosets were observed for four
      weeks before and four weeks after the birth of infants. The animals were kept in
      individual outdoor cages of the Nucleo de Primatologia, under environmental
      conditions. The time spent in proximity was mainly attributable to the initiative
      of females before parturition and the initiative of males after the offspring
      arrived. Males were groomed more before than after the birth of infants. In
      contrast, the amount of grooming received by females was the same in the two
      situations. These observations suggest that the relationship within pairs of
      common marmosets is slightly modified by the birth of infants and indicates that
      males and females could be using different strategies to enhance their
      reproductive success.

PMID- 7581019
TI  - Effect of pimozide on the increase of muscarinic receptors caused by mazindol and
      apomorphine in the rat cerebral motor cortex.
AB  - The effects of pimozide, mazindol and apomorphine on muscarinic receptors in
      homogenates of rat cerebral motor cortex were measured by binding assays, using
      3H-N-methylscopolamine (3H-NMS) alone as ligand (for the measurement of M1- and
      M2-like receptors) or in the presence of carbachol or pirenzepine for
      determination of M1- and M2-like receptors, respectively. Female Wistar rats (150
      g) were treated daily for one week with pimozide, a dopaminergic antagonist (10
      and 20 mg/kg, po, by gavage), or with apomorphine (1 mg/kg, ip). In another set
      of experiments, animals were treated with pimozide and 30 min later with mazindol
      (10 mg/kg, po, by gavage) or apomorphine. The drugs were administered daily for
      one week. Controls received the same volume of saline. 3H-NMS binding was
      increased from the control value of 418 +/- 17 to 548 +/- 42 fmol/mg protein by
      administration of mazindol (10 mg/kg) but binding was reduced to 360 +/- 11
      fmol/mg protein upon administration of pimozide (20 mg/kg) plus mazindol (10
      mg/kg). Similarly 10 mg/kg pimozide reduced the increase in M1-like receptors
      caused by mazindol from 262 +/- 31 to 220 +/- 20 fmol/mg protein. Although 20
      mg/kg pimozide alone produced a decrease in M1- plus M2-like receptors (from 418
      +/- 17 to 348 +/- 22 fmol/mg protein), its action was preferentially on M2-like
      receptors, decreasing them from 148 +/- 10 to 111 +/- 15 fmol/mg protein in the
      control and treated groups, respectively. At the higher dose, 20 mg/kg pimozide
      also inhibited the 3H-NMS binding (M1- plus M2-like receptors) in the presence of
      apomorphine (263 +/- 25 vs 418 +/- 17 fmol/mg protein.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7581021
TI  - Effects of norethisterone acetate and tamoxifen on serum prolactin levels,
      uterine growth and on the presence of uterine immunoreactive prolactin in
      estradiol-treated ovariectomized rats.
AB  - The aim of the present work was to study the effects of the antiestrogen
      tamoxifen (TAM), of progestin norethisterone acetate (NA) and of their
      combination on serum prolactin levels, uterine growth and the presence of uterine
      immunoreactive prolactin in estradiol-treated rats. Ovariectomized female Wistar
      rats were injected sc with estradiol valerate (VE, 50 micrograms/rat per week) or
      oil vehicle. During the second week, estradiol-treated rats also received NA
      (0.12 or 1.0 mg/rat, sc, daily) or TAM (0.06 mg/rat) alone or in combination with
      NA (0.12 mg). Serum prolactin levels were suppressed to the same extent in the
      TAM- and 1.0 mg NA-treated groups compared with rats given estrogen alone (2.3 +/
      0.3 and 5.6 +/- 1.5 ng/ml for TAM and NA groups vs 39.7 +/- 3.6 ng/ml for VE
      groups, P < 0.05). Except for the lowest dose of NA, uterine wet weight and DNA
      content were significantly reduced in all groups compared to estradiol alone
      (236.8 +/- 18.0 and 295.6 +/- 27.8 mg vs 309.4 +/- 32.2 mg for uterine weight in
      TAM and NA groups vs VE, respectively, P < 0.05; and 1.14 +/- 0.05 and 0.93 +/-
      0.04 mg/uterus vs 1.33 +/- 0.06 mg/uterus for uterine DNA in TAM and NA groups vs
      VE groups). The combination of NA and TAM resulted in a higher degree of
      suppression of uterine growth than when each drug was used alone, indicating an
      additive antiproliferative effect of NA and TAM. Although no prolactin
      immunostaining was detected in the uterus of rats treated with estradiol, uterine
      immunoreactive prolactin was identified in those treated with NA, TAM or
      both.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581020
TI  - Pertussis toxin from Bordetella pertussis blocks neutrophil migration and
      neutrophil-dependent edema in response to inflammation.
AB  - Pertussis toxin (Ptx) is a hexameric protein with classical AB architecture
      produced by Bordetella pertussis. The aim of this study was to investigate the
      effect of Ptx on migration of polymorphonuclear leukocytes to site of
      inflammation and on cell-dependent edema. Ptx was purified from the supernatant
      of the culture medium of B. pertussis using hydroxylapatite chromatography and
      fetuin affinity chromatography. Ptx induced a maximal clustering of Chinese
      hamster ovary cells at concentrations as low as 0.1 ng/ml. Intravenous injection
      of Ptx (400 ng) significantly blocked the neutrophil migration induced by 200 ng
      of lipopolysaccharide (LPS from E. coli O111:B4; 2.27 +/- 0.13 vs 0.61 +/- 0.16
      per 10(6) neutrophils/ml; P < 0.001; N = 5) and by 200 ng of formyl-methionyl
      leucyl-phenylalanine (fMLP; 2.53 +/- 0.45 vs 0.75 +/- 0.14 per 10(6)
      neutrophils/ml; P < 0.01; N = 6) into the peritoneal cavities of male Wistar rats
      (weighing 150-180 g). In addition, Ptx (400 ng) pretreatment also blocked the
      edema induced by intraplantar injection of 100 micrograms carrageenin (delta
      increase in volume: 0.667 +/- 0.087 vs 0.313 +/- 0.058 ml; P < 0.01; N = 5) but
      not the edema induced by 100 micrograms dextran (delta increase in volume: 0.537
      +/- 0.06 vs 0.385 +/- 0.076 ml; P > 0.05; N = 5). These data demonstrate that Ptx
      blocked neutrophil migration induced by a direct fMLP stimulus of a site of
      inflammation. In addition, this toxin blocks the indirect stimulus of LPS on
      neutrophil migration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581022
TI  - Effect of cyclophosphamide on the binding of 99mTcO-4 and 99mTc-MDP to blood
      cells and plasma proteins.
AB  - Since the introduction of technetium-99m (99mTc) and its rapid acceptance as a
      tool in nuclear medicine, very little information is available about its
      biological action as 99mTc-radiopharmaceuticals. We have determined if
      cyclophosphamide, an alkylating agent, used in oncology as a chemotherapeutic
      drug, modifies the binding of 99mTcO-4 and 99mTc-MDP (99mTc-methylenediphosphonic
      acid) to blood cells and to plasma proteins. The radiopharmaceuticals were
      injected intravenously (iv) into SW-55 mice (male and female, weight 25 g) and
      samples of plasma and blood cells were separated. Cyclophosphamide (50
      micrograms) was injected iv 1 h before the radiopharmaceuticals. Samples of
      plasma and blood cells were also precipitated with 5% trichloroacetic acid and
      soluble and insoluble fractions were isolated. The following results were
      obtained: 1) cyclophosphamide did not alter (0.25 to 8 h) percent radioactivity
      of 99mTcO-4 in plasma or blood cells but increased the binding of 99mTc-MDP to
      blood cells; 2) cyclophosphamide did not alter (0.25 to 8 h) the binding of
      99mTcO-4 in insoluble fraction of plasma and decreased (1 to 4 h) percent
      radioactivity of 99mTc-MDP in the insoluble fraction of plasma; 3)
      cyclophosphamide increased (0.25 to 4 h) percent radioactivity of 99mTcO-4 in the
      insoluble fraction of blood cells but did not alter the binding of 99mTc-MDP.
      Cyclophosphamide and/or its metabolites modified the effective half-life of these
      radiopharmaceuticals (to 99mTcO-4 was increased 2.3 to 3.4 h and to 99mTc-MDP was
      decreased 3.3 to 2.1 h) and possibly increased the permeability of blood cells to
      99mTcO-4.

PMID- 7581023
TI  - Serum concentration and increased temperature alter Mayaro virus RNA and protein
      synthesis in Aedes albopictus (mosquito)-infected cells.
AB  - We have previously shown the inhibition of Mayaro virus multiplication in Aedes
      albopictus-infected cells maintained at a supraoptimal temperature for growth (37
      degrees C) and a stimulation of virus production in response to high serum
      concentrations in the incubation medium. In the present study, we addressed the
      question of how the effect of continuous heat stress and high serum concentration
      soon after infection interfere with virus macromolecule synthesis. Cells
      maintained at 28 degrees C in the presence of 2% serum synthesized a viral
      genomic RNA of 12 kb and a subgenomic RNA of 5.2 kb 6 h postinfection. Analysis
      of the protein profile showed the presence of the viral nucleocapsid protein of
      34 kDa (P34). However, if infected cells were maintained at 37 degrees C, a smear
      starting immediately below the 5.2-kb RNA was noticed and the viral P34 was not
      detected by SDS-PAGE. Addition of 10% serum to the growth medium of infected
      cells maintained at 37 degrees C results in a viral RNA profile and protein
      synthesis similar to those observed in cultures kept at 28 degrees C, i.e., the
      smear was not observed and the P34 protein was detected. The results suggest that
      the inhibition of virus multiplication by temperature may be related to the
      inhibition of viral nonstructural protein synthesis early during infection. The
      presence of high serum levels in the incubation medium protects macromolecule
      synthesis against heat stress.

PMID- 7581024
TI  - The CD4+ T-cell network and the cytokine profile after HIV-1 infection.
AB  - The present article discusses CD4+ T-cell interaction and cytokine production
      after HIV-1 infection and progression to AIDS. On the basis of the experience of
      the author with biological fluids obtained from patients suspected of having AIDS
      and the recently available data concerning this matter, a model is proposed for
      the CD4+ T-cells network and CD4+ T-cells destruction during this infection. The
      mechanism of cellular killing involves apoptosis and preferential destruction of
      activated TH0/TH2-type cells. This type of cells is generated as an immune
      response to HIV-1 itself or to allergens and helminth infestations. The virus
      replicates more effectively in activated TH0/TH2-type cells and this contributes
      to the development of full-blown AIDS. The author has previously proposed the
      hypothesis of an elevation in IL-5 production during later stages of the disease
      and the use of eosinophilia of unknown etiology as a prognostic marker of AIDS in
      developing countries (Caterino-de-Araujo (1994). Immunology Today, 15: 498-499).
      At the present time, this proposition is confirmed and the use of eosinophilia as
      an indicator of a shift to a TH0/TH2-type response that predicts progression to
      AIDS is justified.

PMID- 7581025
TI  - Prostaglandin A1 inhibits replication of Mayaro virus in Aedes albopictus cells.
AB  - Prostaglandin A1 (PGA1) reduced Mayaro virus replication in Aedes albopictus
      (mosquito) cells in culture. The highest nontoxic dose of PGA1, 7.5 microM,
      decreased virus production by 90%. In Mayaro virus-infected cells, PGA1 inhibited
      virus-specific protein synthesis. However, in mock-infected cells the presence of
      PGA1 stimulated the synthesis of several proteins with molecular masses of 70, 57
      and 23 kDa, respectively. The data obtained from this study show that PGA1 plays
      a role in the metabolic regulation of Aedes albopictus cells, blocking the
      synthesis of Mayaro virus and inducing the synthesis of cellular polypeptides.

PMID- 7581026
TI  - Does gene palB regulate the transcription or the post-translational modification
      of Pi-repressible phosphatases of Aspergillus nidulans?
AB  - When grown on low-Pi medium, the chaA1 pabaA1 palB7 mutant of Aspergillus
      nidulans excretes an acid phosphatase with steady-state kinetic properties,
      temperature sensitivity and electrophoretic mobility different from those of the
      enzyme excreted by the pabaA1 strain. The enzyme excreted by the pabaA1 strain at
      pH 6.5 showed PNP-P activity with negative cooperativity (K0.5 = 0.87 +/- 0.06
      mM, n = 0.68 +/- 0.03) whereas the enzyme excreted by the chaA1 pabaA1 palB7
      mutant showed Michaelian kinetics (Km = 0.46 +/- 0.03 mM, n = 1.00 +/- 0.02). The
      apparent half-lives at 60 degrees C, pH 5.5, of acid phosphatase excreted by the
      pabaA1 and chaA1 pabaA1 palB7 strains were 58.6 +/- 4.9 min and 21.5 +/- 1.8 min,
      respectively. Furthermore, the electrophoretic mobility of acid phosphatases
      excreted by the palA1, palB7, palC4, palE11 and palF15 mutants of A. nidulans was
      altered and differed from the electrophoretic mobility of the enzyme excreted by
      the wild-type strain. Also, the palB7 mutation altered the electrophoretic
      pattern of acid phosphatases synthesized on high-Pi medium. These results are
      compatible with the post-translational modifications in the Pi-repressible
      phosphatases rather than with the action of gene palB in controlling the
      transcription of structural genes of these enzymes.

PMID- 7581027
TI  - Effects of dietary protein, angiotensin I converting enzyme inhibition and
      mesangial overload on the progression of adriamycin-induced nephropathy.
AB  - Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions
      in rats, resulting in persistent proteinuria and glomerulosclerosis. We studied
      the effects of dietary protein and of an angiotensin I converting enzyme
      inhibitor on the progression of this nephropathy and the evolution of the
      histological lesions, as well as mesangial macromolecule flow. Adriamycin
      nephropathy was induced by injecting a single iv dose of adriamycin (3 mg/kg body
      weight) into the tail vein of male Wistar rats (weight, 180-200 g). In Experiment
      I animals with adriamycin-induced nephropathy were fed diets containing 6% (Low
      Protein Diet Group = LPDG), 20% (Normal-Protein Diet Group = NPDG) and 40% (High
      Protein Diet Group = HPDG) protein and were observed for 30 weeks. In Experiment
      II the rats with adriamycin nephropathy were divided into 2 groups: ADR, that
      received adriamycin alone, and ADR-ENA, that received adriamycin plus enalapril,
      an angiotensin I converting enzyme inhibitor. The animals were sacrificed after a
      24-week observation period. Six hours before sacrifice the animals were injected
      with 131I-ferritin and the amount of 131I-ferritin in the glomeruli was measured.
      In Experiment III, renal histology was performed 4, 8 and 16 weeks after
      adriamycin injection. At the end of Experiment I the tubulointerstitial lesion
      index was 2 for LPDG, 8 for NPDG, and 7.5 for HPDG (P < 0.05); the frequency of
      glomerulosclerosis was 19 +/- 6.1% in LPDG, 42.6 +/- 6% in NPDG, and 54 +/- 9% in
      HPDG (P < 0.05); and proteinuria was 61.1 +/- 25 mg/24 h in LPDG, 218.7 +/- 27.5
      mg/24 h in NPDG, and 324.5 +/- 64.8 mg/24 h in HPDG (P < 0.05). In Experiment II,
      at sacrifice, 24-h proteinuria was 189 +/- 16.1 mg in ADR, and 216 +/- 26.1 mg in
      ADR-ENA (P > 0.05); the tubulointerstitial lesion index was 5 for ADR, and 5 for
      ADR-ENA (P > 0.05); the frequency of glomerulosclerosis was 40 +/- 5.2% in ADR
      and 44 +/- 6% in ADR-ENA (P > 0.05); the amount of 131I-ferritin in the mesangium
      was 214.26 +/- 22.71 cpm/mg protein in ADR and 253.77 +/- 69.72 cpm/mg protein in
      ADR-ENA (P > 0.05). In Experiment III, sequential histological analysis revealed
      an acute tubulointerstitial cellular infiltrate at week 4, which was decreased at
      week 8. Tubular casts and dilatation were first seen at week 8 and increased at
      week 16 when few glomerular lesions were found.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7581028
TI  - Detection and isolation of human T-cell leukemia/lymphoma virus type I (HTLV-I)
      from cultured lymphocytes of a Brazilian TSP/HAM patient.
AB  - Some Brazilian regions are considered to be endemic for human T-cell
      leukemia/lymphoma virus type I (HTLV-I) infection. Several studies have shown a
      high prevalence of HTLV-I infection among different groups such as blood donors,
      hemophiliacs and patients suffering from hematological and neurological diseases.
      Cases of adult T-cell leukemia/lymphoma as well as tropical spastic
      paraparesis/HTLV-I-associated myelopathy (TSP/HAM) have already been described in
      Brazil. We report the isolation of an HTLV-I strain from cultured lymphocytes of
      a TSP/HAM patient. An IL-2-dependent HTLV-I-infected T-cell line (ROB) expressing
      viral antigens was established and reverse transcriptase activity could be
      detected in the culture supernatant. Ultrastructural analysis showed immature and
      mature HTLV retrovirus particles. Finally, HTLV-I provirus type I was
      demonstrated by the polymerase chain reaction. This is the first isolation
      completely carried out in Latin America. The molecular analysis of viral strains,
      now in progress, should clarify the molecular epidemiology of HTLV-I in Brazil.

PMID- 7581030
TI  - Health problems of Callithrix jacchus in captivity.
AB  - A 20-year retrospective study was carried out to determine the prevalence of
      diseases occurring in 265 (155 males and 110 females) common marmosets
      (Callithrix jacchus), kept at the Sao Paulo Zoo. A total of 564 clinical
      disorders were detected: digestive problems, 50.2% (protozoa, 44.3%; helminths,
      26.3%; bacteria, 7.0%; non-especific causes, 22.4%); respiratory problems
      (pneumonia), 16.3%; injuries, 13.8%; nutritional deficiency, 4.4%; reproductive
      problems (obstetrical) 2.5%; septicemia, 1.6%; circulatory problems, 1.6%;
      sporadic cases, 4.0%; inconclusive cases, 5.5%. Little attention has been paid to
      the sanitary care of marmosets in Brazil. Since most of the available information
      comes from the international literature, the occurrence of major diseases and
      their etiological agents in Brazil are relevant data.

PMID- 7581029
TI  - Frequency of cholelithiasis in alcoholics.
AB  - In order to determine the frequency of biliary lithiasis in alcoholic patients
      without signs of hepatic cirrhosis, we submitted 106 male alcoholics (mean age,
      42.2 +/- 11.2 years) to ultrasound examination of the biliary system.
      Cholelithiasis was present in 6 (5.6%). We did not observe any association
      between the quantity of ethanol consumed and/or the time of consumption and the
      presence of cholelithiasis. There was no significant difference between the
      frequency of cholelithiasis in these patients and that found in autopsies carried
      out on 716 male patients (6%) at the Hospital de Clinicas, Universidade Federal
      de Uberlandia, during the period 1982 to 1993. Thus, we conclude that in the
      cases we examined, alcoholism did not represent a risk factor for biliary
      lithogenesis.

PMID- 7581031
TI  - Jejunal absorption of trypsin in rat and guinea pig.
AB  - Gut absorption is one of the first requirements for the study of the mechanism of
      a possible anti-inflammatory action of proteases, such as orally administered
      trypsin. Porcine trypsin absorption was studied in isolated jejunal loops of rats
      (female Holtzman and male Wistar) and guinea pigs (males) by open-loop perfusion.
      Trypsin was dissolved in Tyrode solution and the solution perfused at a rate of
      0.5 ml/min, at 37 degrees C. Trypsin activity, total protein, and sodium and
      potassium concentrations were assayed in the jejunal effluent; the values were
      unchanged throughout the experiments, which lasted 45 to 120 min. Using a high
      sensitivity ELISA (i.e. pg/ml), trypsin absorption could be demonstrated by
      determination of the enzyme in the mesenteric venous blood (samples of 0.5 ml);
      the enzyme concentration increased with time of perfusion. The linear range
      specificity for intact trypsin varied from 1 to 500 ng/well. In this assay
      polyclonal antibodies prepared against trypsin-TLCK were utilized. Whereas
      trypsin concentration in the perfused lumen was practically constant at 0.12
      mg/ml, the concentration of absorbed trypsin in mesenteric vein blood increased
      from about 100 ng/ml at time zero to 1.8 micrograms/ml, after 45 min of
      perfusion. Histological and ultrastructural examination of the jejunal mucosa
      before and after perfusion revealed that the brush-border, basal membrane, and
      junctional complexes were fully preserved, thus eliminating the possibility that
      trypsin might have destroyed the structures, thereby reaching the blood
      circulation. The present data indicate that micrograms quantities of trypsin were
      absorbed by the isolated jejunal loop of the rat.

PMID- 7581032
TI  - The effects of endothelin on vascular tonus.
AB  - Using front-surface fluorometry and fura-2, the effect of endothelin (ET) on the
      cytosolic Ca concentration, (Ca)i, in smooth muscle cells and endothelial cells
      was determined. Both the contraction of smooth muscle cells and the release of
      endothelium-derived relaxing factor (EDRF) from endothelial cells are regulated
      by changes in (Ca)i. During contractions induced by U-46619, a thromboxane A2
      analog, low doses of ET-1 induced an EDRF-dependent reduction of (Ca)i and force
      in porcine coronary arterial smooth muscles. Using porcine aortic valvular
      strips, we recorded the signals of (Ca)i in endothelial cells in situ. ET-1
      induced an influx of Ca, which was markedly inhibited by pertussis toxin (IAP),
      thus indicating that this influx was regulated by an IAP-sensitive G-protein. BQ
      123, a selective ETA receptor antagonist, partially inhibited the elevation of
      (Ca)i induced by ET-1, but did not affect the elevation of (Ca)i induced by ET-3.
      The sequence of cDNA encoding the porcine ETA receptor has been previously
      determined, and RT-PCR confirmed that ETA receptor mRNA was present in the
      endothelial cells on the aortic side of the valvular strips. Therefore, in
      addition to ETB receptors, functioning ETA receptors and ETA receptor mRNA can
      also be found in endothelial cells in situ. Thus, ET-1 may play an important role
      in controlling the coronary artery tonus not only by acting directly on smooth
      muscle cells to increase the force in a paracrine manner, but also by acting on
      endothelial cells to release EDRF in an autocrine manner, resulting in relaxation
      of smooth muscle cells.

PMID- 7581033
TI  - Inhibition of enteropathogenic Escherichia coli adhesion to HeLa cells by serum
      of infants with diarrhea and by cord serum.
AB  - We have studied the effect of serum from infants with diarrhea and of cord serum
      on the localized adherence of enteropathogenic Escherichia coli (EPEC) to HeLa
      cells. Serum samples from 16 infants with diarrhea due to EPEC of serotypes
      O55:H6, O111: H-, O111:H2, O119:H6 and O142:H6 were used. The adherence ability
      of EPEC strains belonging to serotypes identical to (homologous) or different
      from (heterologous) those isolated from the infants' feces was highly inhibited
      by samples of infant serum collected both during the acute phase of the illness
      and upon discharge from the hospital. These data confirm the development of
      antibodies against EPEC adhesins and the cross-reaction between different EPEC
      serotypes. Cord serum inhibited the localized adherence of EPEC strains at
      different levels according to the serotype of the strain studied. These results
      suggest that the placental transfer of adhesin-related antibodies does not
      protect the newborn against EPEC infections, since half of our patients were less
      than 30 days old.

PMID- 7581034
TI  - Effect of manipulation of the GABA system on dopamine-related behaviors.
AB  - The interaction between GABAergic and dopaminergic systems within the central
      nervous system was investigated in rats using the open-field apparatus and
      apomorphine-induced stereotypy, and in mice using haloperidol-induced catalepsy.
      The single intraperitoneal administration of baclofen 3.0 mg/kg, 4,5,6,7
      tetrahydroisoxasolo-(5,4-c) piridin-3-ol (THIP) 10.0 mg/kg and picrotoxin 2.0
      mg/kg decreased both ambulation and rearing frequencies of the rats in the open
      field; only the GABA agonists increased the duration of animal immobility. THIP
      (10.0 mg/kg) increased the duration of haloperidol-induced catalepsy. For
      apomorphine-induced stereotypy, baclofen 3.0 mg/kg and picrotoxin 1.0 mg/kg
      induced a significant leftward displacement of the control dose-response curve
      constructed for apomorphine (0.1-10 mg/kg) in relation to the control. In
      addition, baclofen, THIP, picrotoxin and 3-mercaptopropionic acid (3-MPA) 10.0
      mg/kg decreased both rearing and sniffing behaviors elicited by apomorphine and
      increased licking and/or gnawing. Different mechanisms seem to be involved in the
      similar effects induced by GABA agonists and antagonists. Picrotoxin induced
      stereotyped movements per se with a dose-dependent effect, but baclofen and THIP
      did not. The present data suggest that GABA manipulation facilitates the
      progressive activation of the different dopaminergic pathways involved in
      stereotyped behaviors, thus increasing those stereotyped components (gnawing and
      licking) that appear after a high level of activation of dopaminergic pathways.

PMID- 7581035
TI  - A response to the paper entitled "Productivity versus promised results: one of
      the dilemmas of biotechnology in Brazil".

PMID- 7581036
TI  - Yeast RNA polymerase III: transcription complexes and RNA synthesis.
AB  - In this article we review and summarize salient features of the mechanism of
      transcription by eukaryotic RNA polymerase III, focusing a considerable part of
      the account on the work of our laboratory, dealing with Saccharomyces cerevisiae,
      but emphasizing properties that are common to all eukaryotic RNA polymerases. The
      following topics are briefly discussed: promoter structure; transcription
      factors; internal structure of transcription complexes and DNA-protein
      interactions; U6 genes; promoter opening and RNA chain elongation; hydrolytic RNA
      retraction.

PMID- 7581037
TI  - The olfactory and visual systems are closely related in Drosophila.
AB  - The olfactory and visual systems of Drosophila have similar developmental
      origins: both derived from the eye-antennal imaginal disc. Moreover, there are
      commonalities in the cellular, molecular, and genetic underpinnings of their
      development. For example, the developmental program of both systems entails cell
      death, which depends upon the irregular chiasm C-roughest gene, and both systems
      require the lozenge gene for normal pattern formation. The rdgB (retinal
      degeneration B) gene is required not only for the maintenance and physiology of
      the visual system, but also for olfactory physiology. This gene has been shown by
      others to encode a phosphatidylinositol transfer protein; it is expressed both in
      visual and olfactory organs. The norpA gene, which encodes a phospholipase C, is
      also required both for phototransduction and for odorant response in one
      olfactory organ. Thus some genes are required in both systems; in addition, at
      least one olfactory gene that is apparently not expressed in the visual system
      may have a visual system counterpart. These and other similarities are considered
      in terms of the evolutionary relationship between the two systems. We conclude
      that analysis of the visual system is likely to provide insight into the
      development and function of the olfactory system, and vice versa.

PMID- 7581038
TI  - Trehalose metabolism--new horizons in technological applications.
AB  - Trehalose is responsible for the survival of anhydrobiotic organisms when under
      stress. Trehalose is a unique, non-reducing, extremely stable disaccharide which
      is able to protect proteins and membranes from damage caused by freezing, high
      temperatures and dehydration. Yeasts accumulate large amounts of trehalose and
      constitute excellent models for studying the response of eucaryotic cells to
      diverse stresses. The regulation of trehalose metabolism is reviewed and new
      technological applications for preservation of biological materials are
      discussed.

PMID- 7581039
TI  - Purification and properties of storage proteins (vicilins) from cowpea (Vigna
      unguiculata) seeds which are susceptible or resistant to the bruchid beetle
      Callosobruchus maculatus.
AB  - Vicilins (7S storage proteins) from seeds of cowpea (Vigna unguiculata) cultivars
      which are susceptible or resistant to the bruchid beetle C. maculatus were
      purified by size-exclusion and ion-exchange chromatography. The vicilins were
      partially characterized by polyacrylamide gel electrophoresis under both
      denaturing and nondenaturing conditions, by Western blotting and by amino acid
      analysis. The variant vicilins from C. maculatus-resistant seeds do not differ
      appreciably from vicilins from susceptible seeds by these criteria except that
      they are more strongly bound to DEAE-Sepharose, suggesting differences in charge
      between the various molecules.

PMID- 7581040
TI  - Isolation of the lectin and an L4 isolectin from Phaseolus vulgaris by affinity
      chromatography on insoluble ovomucoid.
AB  - Lectins from extracts of Phaseolus vulgaris seeds have potent cell-agglutinating
      and lymphocyte-stimulating activity. An affinity adsorbent for lectins with
      specificity for the oligosaccharide structure was prepared by transforming
      ovomucoid, an oligosaccharide-rich glycoprotein, into an insoluble and stable
      gel. The ovomucoid was made insoluble by boiling a 20% solution (200 mg/ml) in
      0.1 M Tris-HCl, pH 8.9, for 20 min. This insoluble gel was desialylated by
      treatment with 50 mN sulfuric acid for 1 h at 90 degrees C and fixed with 1%
      glutaraldehyde, pH 7.4, for 10 min. The Phaseolus lectin and the L4 isolectin
      could be isolated essentially in a single-step procedure, using different eluting
      conditions: 50 mM sodium formate buffer, pH 3.0, was used for PHA elution; a
      different column was eluted with 15 mM sodium tetraborate, pH 8.0, for desorbed
      L4 isolectin. Polyacrylamide gel electrophoresis of the lectin showed five
      distinct bands, whereas the L4 isolectin only presented one band. From 250 mg of
      saturated column, 8.25 mg of PHA was isolated. This adsorbent could be used
      several times with little change in binding capacity or selectivity.

PMID- 7581041
TI  - Genomic characterization of type 3 polioviruses isolated from vaccine-associated
      poliomyelitis cases in Brazil.
AB  - Eight strains of P3/Sabin-related polioviruses were analyzed; four from
      persistent paralytic poliomyelitis cases classified as vaccine associated, one
      from a transient paralysis case classified as transverse myelitis, one from a
      transient paralysis case classified as Guillain-Barre syndrome, one from a
      transient facial paralysis case, and one from a healthy vaccine. The serotypes of
      the viral isolates were identified by the neutralization test with hyperimmune
      equine sera and the relationship of the isolates with the P3/Sabin strain was
      demonstrated by molecular hybridization of the viral RNA of the isolates with a
      P3/Sabin-specific probe. The P3/Sabin relationship was confirmed by PCR, using a
      pair of specific primers for P3/Sabin-related isolates. The available data
      indicate that a U-->C mutation at nucleotide 472 in the 5' noncoding region of
      the genome of the type 3 Sabin strain increases the neurovirulence of this strain
      and this mutation was observed in all type 3 isolates from vaccine-associated
      cases. These eight P3/Sabin-related isolates were partially sequenced in the 5'
      noncoding region and seven presented a U-->C mutation at nucleotide 472, except
      the isolate from a transient paralysis case classified as transverse myelitis,
      that maintained a U at nucleotide 472. Although this virus maintaining U at
      nucleotide 472 may not be the etiological agent of the disease, the possibility
      that the virus was the causative agent of the disease could not be ruled out.

PMID- 7581042
TI  - Peripheral glucose metabolism in patients with chronic renal failure.
AB  - The present study was designed to determine the effect of chronic renal failure
      on forearm muscle glucose uptake and oxidation during the postabsorptive state
      and after an oral glucose challenge. Twelve normal subjects and sixteen patients
      with chronic renal failure were studied after an overnight fast (12-14 h) and for
      3 h after the ingestion of 75 g of glucose. Peripheral glucose metabolism was
      analyzed by the forearm technique to estimate muscle exchange of substrate
      combined with indirect calorimetry. Decreased forearm glucose uptake was observed
      in uremic patients compared to normal subjects (91.5 +/- 11.4 vs 154.8 +/- 7.8 mg
      100 ml forearm-1 3 h-1) with diminished nonoxidative glucose metabolism (69.4 +/-
      12.1 vs 117.2 +/- 12.8 mg 100 ml forearm-1 3 h-1). Muscle glucose oxidation did
      not differ significantly between groups. Both serum free fatty acid levels and
      lipid oxidation rates were similar in the normal subjects and the uremic
      patients, and declined in a similar fashion after glucose ingestion. Basal serum
      insulin levels did not differ significantly between normal and uremic patients,
      whereas the insulinemic response to glucose load was greater among the patients
      with chronic renal failure. These data show that insulin resistance occurring in
      patients with chronic renal failure is accompanied by impaired muscle glucose
      uptake and nonoxidative glucose metabolism.

PMID- 7581043
TI  - Granulomatous reaction in the hamster cheek pouch induced by killed
      Paracoccidioides brasiliensis.
AB  - We have studied the role of Paracoccidioides brasiliensis viability in the
      morphology of paracoccidioidomycotic granulomas in the hamster cheek pouch, an
      immunologically privileged site. Naive (N = 75) and previously sensitized (N =
      50) two-month old male hamsters (Mesocricetus auratus) were inoculated into the
      pouch with 5 x 10(5) live or heat- or formalin-killed fungi. Previously
      sensitized animals presented a positive footpad test and immunodiffusion
      demonstrable antibodies (titer 1/32), at the time of sacrifice; naive animals
      were always negative for those immunological tests. The histological results
      showed that, like viable P. brasiliensis, killed fungi evoke typical epithelioid
      granulomas in 100% of animals, even in the absence of immunodiffusion or footpad
      test detectable immune response. The granulomas elicited by killed fungi were
      devoid of giant cells or a mononuclear cell halo, suggesting that live
      proliferating fungi or their products may be involved in these events.

PMID- 7581044
TI  - The effect of serum on in vitro maturation, in vitro fertilization and
      steroidogenesis of bovine oocytes co-cultured with granulosa cells.
AB  - The influence of fetal calf serum alone (FCS) or associated with proestrous
      (FCS+PCS), estrous (FCS+ECS) or metaestrous (FCS+MCS) cow serum added to the
      culture medium and of the steroids produced by co-cultured granulosa cells were
      evaluated in terms of the in vitro maturation (IVM) and fertilization (IVF) of
      bovine oocytes. Supplementation of the medium with FCS+ECS and FCS+MCS resulted
      in higher proportions of oocytes that reached metaphase II (96.0% and 93.3%,
      respectively) and in higher proportions of embryos that reached the four- and
      eight-cell/morula stages (51.9% and 65.6%, respectively), whereas the
      supplementation with FCS and FCS+PCS resulted in only 79.2% and 67.5%,
      respectively, of matured oocytes and 26.7% and 34.3%, respectively, of cleaved
      embryos. These findings show that the best IVM and IVF were obtained at lower
      concentrations of estradiol produced by co-cultured granulosa cells
      (supplementation with FCS+ECS: 10.3 ng/ml and FCS+MCS: 2.1 ng/ml), whereas the
      worst results in IVM and IVF occurred at higher concentrations of estradiol that
      were obtained with FCS (33.1 ng/ml) and FCS+PCS (19.9 ng/ml) supplementation.
      These data suggest an inhibitory effect of estradiol on resumption of oocyte
      meiosis in vitro.

PMID- 7581045
TI  - Diabetes and experimental pregnancy in rats: course of maternal blood glucose
      levels and its repercussions on the blood glucose levels and pancreas of newborn
      pups.
AB  - The objective of the present investigation was to determine the course of
      maternal blood glucose levels in pregnant rats and its repercussions on the
      glucose levels and pancreas of their newborn pups. Diabetes was induced by
      alloxan (42 mg/kg body weight) and streptozotocin (40 mg/kg). Sixty-two pregnant
      Wistar rats weighing 180 to 250 g were divided into a control group and two
      groups with moderate (120 to 200 mg/dl glucose) and severe diabetes (greater than
      200 mg/dl glucose), respectively. Blood glucose levels were measured in the dams
      on the 1st, 14th, and 21st days of pregnancy and in the pups at birth. The
      results were pooled for each litter. The fetal pancreases were removed after
      cesarian section performed on the 21st day of pregnancy, pooled for each litter
      and processed for histopathologic examination by light microscopy. Maternal blood
      glucose levels were significantly increased compared with the first day of
      pregnancy in both normal and diabetic rats starting on the 14th day of pregnancy.
      Fetal blood glucose levels correlated with maternal levels. The histopathologic
      changes characterized by vacuolization and basophilia of the cytoplasm of
      endocrine pancreas of newborn pups from dams with moderate or severe diabetes
      suggested pancreatic hyperactivity.

PMID- 7581046
TI  - Effect of the complement system on the sensitivity of Campylobacter jejuni and
      Campylobacter coli to human blood serum.
AB  - We determined the sensitivity of five strains of Campylobacter jejuni and C. coli
      isolated from children with diarrhea and from chicken feces to normal human blood
      serum (undiluted and at concentrations of 10, 30, 50 and 70%), a
      hypogammaglobulinemic serum and a complement-deficient serum. Both species were
      highly sensitive to the bactericidal activity of human serum, regardless of their
      source. The highest bactericidal activity was observed with pooled fresh normal
      serum, with bacterial survival rates inversely correlated to serum dilutions.
      Inactivated serum had the least bactericidal activity. When complement was
      partially restored to inactivated serum, lower survival rates were observed. The
      hypogammaglobulinemic-normal complement-containing serum had strong bactericidal
      activity whereas the normal immunoglobulin-containing but complement-deficient
      serum had little bactericidal activity. These results suggest that Campylobacter
      may be able to directly activate complement by the alternative pathway.

PMID- 7581047
TI  - Developmental toxicity of lithium treatment at prophylactic levels.
AB  - Lithium (Li+) salts are frequently used in psychiatry and may be administered to
      women in their reproductive years. We have investigated the influence of chronic
      Li+ administration on rat offspring. Pregnant Wistar rats drank either tap water
      ad libitum or 10 mM LiCl, or were water restricted (paired to rats receiving
      LiCl) until pup weaning. Following birth, pups were fostered to form five
      experimental groups (N = numbers of litters): a) Control-S, stressed by water
      restriction (N = 21), b) Li+ during the prenatal and lactating periods (N = 18),
      c) Li+ during the prenatal period only (N = 22), d) Li+ during the lactating
      period only (N = 15), and e) Control-NS no treatment (N = 13). Prenatal water
      restriction or Li+ treatment impaired the performance of the righting reflex,
      altered the number of males born and delayed the final date of eye opening.
      Postnatal water restriction or Li+ treatment of the dams reduced body growth and
      the date of eye opening of pups. No difference was found in the time to pup
      earflap opening, or in the motor coordination test. The specific effect of
      lithium on pups included impairment of the righting reflex, an increase in the
      number of males born, a reduction in body weight at weaning and a delay in the
      eye opening date. The serum Li+ levels of the dams were maintained at
      approximately 0.5 mEq/l. There was an increase in serum potassium, but not
      sodium, concentrations. We conclude that chronic treatment of dams with Li+ in
      amounts similar to those used in the prophylaxis of bipolar disorders aggravated
      the delay in physical and behavioral development of pups produced by stress
      associated with limited water intake and handling.

PMID- 7581048
TI  - Alpha-adrenergic pathways in the lateral hypothalamus are important for the
      dipsogenic effect of carbachol injected into the medial septal area.
AB  - We studied the effect of the alpha 1- and alpha 2-adrenergic receptors of the
      lateral hypothalamus (LH) on the control of water intake induced by injection of
      carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300
      g) implanted with chronic stainless steel cannulae into the LH and MSA. The
      volume of injection was always 1 microliter and was injected over a period of 30
      60 s. For control, 0.15 M NaCl was used. Clonidine (20 nmol) but not
      phenylephrine (160 nmol) injected into the LH inhibited water intake induced by
      injection of carbachol (2 nmol) into the MSA, from 5.4 +/- 1.2 ml/h to 0.3 +/-
      0.1 and 3.0 +/- 0.9 ml/h, respectively (N = 26). When we injected yohimbine (80
      nmol) + clonidine (20 nmol) and prazosin (40 nmol) + clonidine (20 nmol) into the
      LH, water intake induced by injection of carbachol into the MSA was inhibited
      from 5.4 +/- 1.2 ml/h to 0.8 +/- 0.5 and 0.3 +/- 0.2 ml/h, respectively (N = 19).
      Water intake induced by carbachol (2 nmol) injected into the MSA was decreased by
      previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin
      (40 nmol) + phenylephrine (160 nmol) from 5.4 +/- 1.2 ml/h to 1.0 +/- 0.7 and 1.8
      +/- 0.8 ml/h, respectively (N = 16). The cannula reached both the medial septal
      area in its medial portion and the lateral hypothalamus. It has been suggested
      that the different pathways for induction of drinking converge on a final common
      pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581049
TI  - Localization of NADPH-diaphorase activity in the human visual cortex.
AB  - The present report describes the activity of NADPH-diaphorase (NADPHd) in area 17
      of autopsied normal human visual cortex. Four human brains from autopsy tissue (4
      8 h postmortem) were fixed by immersion in 4% paraformaldehyde in 0.1 M sodium
      phosphate buffer, pH 7.2-7.4, or in 10% formalin for 24 h. NADPHd histochemistry
      was done using the malic enzyme indirect method. The neuropile pattern of enzyme
      activity presented a clear six-layer appearance. Cell morphology and the laminar
      distribution of 73 NADPHd-positive neurons are described. All neurons found in
      area 17 of human cortex were sparsely spiny or smooth cells, located in all
      cortical layers except layer 4c. Quantitative analysis of the branching pattern
      of the dendritic tree was carried out. A symmetrical pattern was observed with no
      particular dendritic bias except for a few white matter and layer 1 cells. Larger
      dendritic fields were found in white matter cells when compared to the other
      cortical layers. Comparison of cell densities for gray and white matters showed
      that 85% of the NADPHd-positive neurons were located in the white matter. NADPHd
      was colocalized with nitric oxide synthase which produces nitric oxide, a short
      life neuromediator implicated in synaptic plasticity, neuroprotection, and
      neurotoxicity. Thus, the spatial distribution of the NADPHd cells is important
      for posterior functional studies of the neuromediators in the brain.

PMID- 7581050
TI  - Biochemical characterization of NADPH-diaphorase in the chick embryo retina:
      stimulation by calcium ions and inhibition by arginine analogs.
AB  - Nitric oxide is an important intercellular messenger in the central nervous
      system. NADPH-diaphorase, reported to be identical to nitric oxide synthase, is
      present in specific groups of cells in several neural tissues, including the
      retina. We determined NADPH-diaphorase activity in homogenates of the chick
      embryo retina. The enzyme activity was measured spectrophotometrically at 585 nm
      after incubating retinal total homogenates (100-150 micrograms protein) with 1 mM
      NADPH and 0.5 mM nitroblue tetrazolium in 50 mM Tris buffer, pH 8.1, at 37
      degrees C. NADPH-diaphorase was detected in 14-day old retinas and 53-65% of the
      enzyme activity was inhibited by 3 mM NG-nitro-L-arginine (NARG), the arginine
      analog. One mM L-N5-(1-iminoethyl)ornithine (NIO) was the most potent inhibitor
      (63% inhibition) while 3 mM NG-nitro-L-arginine methyl ester (NAME) (33%
      inhibition) and 1 mM NG-monomethyl-L-arginine acetate (NMMA) (14% inhibition)
      were less effective. Enzyme activity was increased by 48% by 2 mM calcium
      chloride, an effect reversed by 1 mM EGTA or EDTA. Basal enzyme levels were also
      partially inhibited by the chelators, indicating the presence of calcium
      dependent and -independent isoforms of nitric oxide synthase in the retina. The
      results show that the NADPH-diaphorase assay is simple and sensitive and that the
      different isoforms of nitric oxide synthase expressed in chick retinal cells
      during development can be demonstrated.

PMID- 7581051
TI  - In vitro effect of cyclophosphamide on the binding of radiopharmaceuticals
      (99mTcO4- and 99mTc-MDP) to blood elements.
AB  - Sodium pertechnetate (99mTcO4-) and many 99mTc-products are the
      radiopharmaceuticals most frequently used in nuclear medicine. Using an in vitro
      model, we evaluated the effect of cyclophosphamide on percent radioactivity of
      99mTcO4- and methylenediphosphonic acid (99mTc-MDP) bound to isolated blood
      elements. Blood samples were incubated with the two radiopharmaceuticals, plasma
      and blood cells were separated and precipitated, and soluble and insoluble
      fractions were separated. To evaluate the effect of cyclophosphamide, blood was
      incubated with this drug 1 h prior to the addition of the radiopharmaceuticals.
      The fraction of 99mTcO4- radioactivity was slightly higher in plasma (61.2 to
      53.8%) than in blood cells (38.8 to 46.2%) up to 6 h and cyclophosphamide did not
      interfere with this distribution. The amount of 99mTc-MDP radioactivity was
      higher in plasma (91.1 to 87.2%) than in blood cells (8.9 to 12.8%) up to 24 h
      and cyclophosphamide did not modify it. The binding of 99mTcO4- to the insoluble
      fraction of plasma (4.9 to 6.1%) was low and cyclophosphamide did not interfere
      with it up to 6 h, but a small blockade (9.8 to 4.8%) was observed at 24 h. From
      3 h on, cyclophosphamide slightly inhibited 99mTcO4- binding to blood cells (23.1
      to 16.6%) and increased it at 24 h (31.2 to 14.3%). Cyclophosphamide did not
      alter 99mTc-MDP binding to the insoluble fraction of blood cells and slightly
      decreased 99mTc-MDP binding to the insoluble fraction of plasma (29.8 to 23.6%)
      up to 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581052
TI  - [Neurogenic mechanisms of asthmatic bronchitis].

PMID- 7581053
TI  - [Influence of bacterial infection and formalin vapors on the course of ovalbumin
      induced experimental bronchospastic reaction in guinea pigs].
AB  - The pathomechanism of the bronchospastic reaction is not fully explained.
      Ovalbumin induced bronchospastic reaction in guinea pigs is widely accepted as a
      classical experimental model and was appleid in this study. The
      bronchoconstriction, bronchial hypersensitivity and humoral immune response were
      measured after bronchial infection and chemical injury by formalin vapours. The
      intensity of the bronchospasm was measured by Lundberg index, the haemolytic
      activity of complement and the level of circulating immune complexes were
      measured at the beginning and at the end of the experiment. The increase of the
      bronchospastic reaction and bronchial hypersensitivity was observed bacterial
      infection and after formalin vapours too. Bronchial infection and chemical
      irritation of bronchial tree lead to the increase of the circulating immune
      complexes level and to the decrease of the haemolytic activity of the complement.

PMID- 7581055
TI  - [Effect of salbutamol inhalation on small airways function in patients with
      sarcoidosis].
AB  - The effect of Salbutamol (Polfa) inhalation on small airway function was studied
      in 20 patients with stage II sarcoidosis and 8 healthy volunteers. MEFV values
      and dynamic compliance were assessed. A significant statistical increase of FEV1,
      MEF50, Cdyn20 and Cdyn60 were seen only in healthy volunteers. In patients with
      sarcoidosis the assessed parameters were not effected by the Salbutamol
      inhalation.

PMID- 7581054
TI  - [Histology of the respiratory system after exposure to bacterial infection and
      formalin vapors used to induce experimental bronchospasm].
AB  - The purpose of the research was to observe the influence of the bacterial
      infection and inhalation vapours on the histologic picture of bronchi and lungs
      in the course on the experimental asthma induced in guinea pigs. The animals were
      divided into 6 groups. The animals were immunized by ovalbumin. Group I was
      control and was subjected to inhalations of physiologic salt solutions. Group II
      was immunized by the soluble of ovalbumin intraperitoneally and was inhaled with
      the solution of ovalbumin. Group III was subjected only to inhalation of the
      ovalbumin. Group IV was inhaled with the solution of formalin alternately. Group
      V experienced only formalin inhalations. Group VI was infected with Pseudomonas
      aeruginosa strain and inhaled with the solution of ovalbumin. On the histologic
      examination of the lung tissue the authors found the atrophy of the lymphatic
      system, the hypertrophy of the mucous membrane and muscular coat of the bronchi,
      the accumulation of large amount of mucus in their lumen and the exfoliation of
      the bronchial epithelium.

PMID- 7581056
TI  - [Evaluation of bradykinin levels and activation of Tame-esterase in Bronchial
      alveolar lavage fluid of patients with bronchial asthma].
AB  - Airway inflammation is a prominent feature of chronic airway disease as asthma
      and chronic bronchitis. Multiply cells released mediators and neurotransmitters
      which are likely to be involved in their origination. The purpose of this study
      was to establish the levels of kinin, albumin, TAME-esterase activity in BAL
      fluid of symptomatic and asymptomatic asthmatic patients and to determinate the
      relationship among mediators. There were significant increases in the mean
      concentrations of kinin, HSA, TAME-esterase activity in BAL fluid from patients
      with asthma, chronic bronchitis, compared with the controls (p < 0.005). Kinin
      mean concentration was in asthmatics 5313, 2 ng/ml, in chronic bronchitis
      patients 6796.2 ng/ml, versus 468.1 ng/ml in control group. TAME-esterase
      activity in investigated group was as follow asthmatics 12666 cmp, CB 15131, 3
      cmp, versus 3695, 5 cmp in controls. We observed good correlation of kinin and
      TAME-esterase with HSA in BAL fluid suggest vascular origin of the mediators. The
      presence of kinins, TAME-esterase in BALs from symptomatic asthmatics and
      patients with chronic bronchitis provide strong evidence that kinins are involved
      in this group of lower airway diseases.

PMID- 7581057
TI  - [Course of non-specific bronchial reactivity to histamine after bronchospasm
      induced by allergen challenge in patients with bronchial asthma].
AB  - Bronchial hyperresponsiveness is the characteristic feature of bronchial asthma.
      Inhalation of allergen can cause dual asthmatic response--early and late
      reaction. Thirteen patients with mild and moderate asthma underwent bronchial
      allergen challenge. Non-specific bronchial reactivity was measured before, 90
      minutes, on the 2nd, 7th, 14th day after provocation. Peak Expiratory Flow was
      measured every hour during 12 hours after challenge to search for late phase
      reaction. Increased bronchial reactivity was discovered as early as 90 minutes
      after challenge, it was still observed on the 2nd and 7th but not on the 14th day
      after allergen provocation. No relationship was found between appearance of late
      asthmatic reaction and increased bronchial reactivity.

PMID- 7581058
TI  - [Effect of loratadine, selective antagonist of histamine H1 receptors, on
      histamine-induced bronchoconstriction].
AB  - The aim of this study was to assess the duration of Loratadine effect on
      histamine H1 receptor in the airway. Six patients with mild or moderate asthma
      were examined. Bronchial reactivity to histamine was measured according to
      Cockcroft. The significant blockade of histamine H1 receptors in airway was
      observed from the 2nd day when 10 mg of Lo was given daily. The maximal
      protection with 10 mg doses was observed after 3-4 days. After another 5-6 days
      without Loratadine bronchial responsiveness return to the initial values. Single
      dose of 30 mg Loratadine given better protection against histamine
      bronchoconstriction than 10 mg given for 5 days. This effect was observed as
      early as 60 minutes after administration of Loratadine.

PMID- 7581059
TI  - [Value of determining the concentration of carcinoembryonic antigen in bronchial
      lavage for diagnosis of lung cancer].
AB  - CEA levels were measured in bronchial lavage in 84 patients with endobronchial
      lung cancer, undergoing diagnostic bronchoscopy. The control group consisted of
      94 patients with nonmalignant lung disease, in whom bronchoalveolar lavage was
      performed. In both groups of patients 100 ml of normal saline solution was used
      during the lavage procedure. CEA levels in lavage fluid and in serum were
      determined with polyclonal (CEA-RIA) and monoclonal antibodies (CEA-EIA).
      Significantly increased CEA levels in lavage fluid were observed in patients with
      lung cancer (97.4 +/- 56.4 ng/ml) in comparison to the patients with nonmalignant
      lung disease (4.2 +/- 6.3 ng/ml). Patients with lung cancer had CEA levels in
      lavage fluid about 30 times higher than in serum. Determination of CEA levels in
      bronchial lavage can be a useful additional diagnostic method in patients with
      lung cancer.

PMID- 7581061
TI  - [Effect of single dose administration of nitrendipine on pulmonary arterial
      pressure measured using doppler echocardiography].
AB  - The effect of a single oral dose of Nitrendipine (20 mg) on mean pulmonary
      arterial pressure was studied in 14 patients with COPD and chronic cor pulmonale
      and 12 patients with COPD and without coexistent cor pulmonale. Parameters were
      assessed with Doppler echocardiography calculating average acceleration time of
      blood from the pulmonary artery. Simultaneously arterial pressure and heart rate
      were determined. The authors found that a single oral dose (20 mg) of
      Nitrendipine significantly lowered elevated pressure in the pulmonary artery
      during at least 6 hours without effecting heart rate.

PMID- 7581060
TI  - [Analysis of course and treatment results after treatment of pulmonary
      tuberculosis with early introduction of interrupted observation--preliminary
      report].
AB  - The results of the treatment 33 patients for smear-positive pulmonary
      tuberculosis with Isoniazid, Rifampicin, Pyrazinamide and Streptomycin
      administrated during first two weeks daily, from 3 to 8 week also with these four
      drugs but in a little higher doses twice weekly and next Isoniazid and Rifampicin
      during 9-26 weeks also twice weekly as in standard Polish model were described.
      After therapy with above described regimen all patients became smear-negative and
      radiological improvement was observed. Drugs in higher doses were well tolerated.
      Only abnormality in laboratory findings was temporary elevated level of uric
      acid, which recovered to normal values before the end of therapy. Costs of
      antituberculous drugs were used in this regimen is approximately 35% lower than
      standard model in Poland.

PMID- 7581062
TI  - [Indications for prophylactic vena cava filters introduced subcutaneously in
      patients with thromboembolic disease--preliminary report].
AB  - In 10 patients with thromboembolic disease 1 Gunther filter and 9 LGM filters
      were inserted. Indications for filter placement were: pulmonary hypertension
      caused by recurrent pulmonary embolism in 3 cases; planned surgery in 2 patients
      with pulmonary embolism and deep venous thrombosis; recurrent pulmonary embolism
      despite of anticoagulant treatment in 2 cases, previously performed thrombo
      endarterectomy in 1 case; contraindications for anticoagulant treatment in 1 case
      and complications of anticoagulant therapy also in 1 case. No serious
      complications after filter placement were observed.

PMID- 7581063
TI  - [Primary pulmonary lymphoma of the peripheral T lymphocyte type].

PMID- 7581064
TI  - [A case of extrapulmonary hamartoma].
AB  - Rare case of hamartoma localised extrapulmonary in the chest cavity is described.
      Clinical evaluation as well as histopathological features were identical with
      typical intrapulmonary hamartomas.

PMID- 7581065
TI  - [Use of nasal intermittent positive pressure ventilation in treatment of
      exacerbation of chronic respiratory insufficiency].
AB  - A case of a 45 year old male with COPD is presented. In the past the patient
      required twice mechanical ventilation. During a current hospitalization Nasal
      Intermittent Positive Pressure Ventilation (NIPPV) was successfully applied. The
      treatment was carried out continuously for 8 days, during the next 7 days for 15
      hours per day, during the next 8 days only at night time. A clinical improvement
      was seen. NIPPV was used for a shorter period of time than the classical
      mechanical ventilation. It was also less expensive.

PMID- 7581066
TI  - [Cholinergic-dependent airway obstruction].

PMID- 7581067
TI  - [Histamine releasing factors and chemotactic factors in evaluation of mucosal
      inflammation in bronchial asthma].

PMID- 7581068
TI  - [Diagnosing bronchospastic states].

PMID- 7581069
TI  - [Asthma and chronic obstructive pulmonary disease. Similarities and differences].

PMID- 7581070
TI  - [Pulmonary lymphomatoid granulomatosis--peripheral T cell lymphoma-
      pathomorphologic characteristics].

PMID- 7581071
TI  - [Coagulation and fibrinolysis parameters in neoplastic pleural exudates].

PMID- 7581072
TI  - [Role of heparin in neoplastic angiogenesis].
AB  - Angiogenesis, the growth of new capillary blood vessels, is a multistep process
      required for tumor growth and metastasis. The significant correlation between
      density of microvessels and occurrence of metastasis was shown in cutaneous
      melanoma, cancers of breast, lung (non-small-cell), and bladder. It has been
      shown that heparin play a crucial role in angiogenesis. In this review the
      mechanism of this regulation was summarized, and it was compared to action of
      specific antagonists of heparin in angiogenesis. It is known that heparin can
      promote this process, but some fractions may not. Knowing the complex action of
      heparin in the angiogenesis, the exact role of heparin in tumor growth and
      metastasis is unknown. Therefore, we suggest that it is needed to confirm if an
      use of heparin for treating patients with cancer can prolong their survival.

PMID- 7581073
TI  - [Mechanisms of radiation to the lung. Pentoxifylline--a new radioprotective
      drug?].

PMID- 7581074
TI  - Severe esophageal stricture after autologous bone marrow transplant.

PMID- 7581076
TI  - 1994 Consensus Conference on Acute GVHD Grading.
AB  - Grading acute graft-versus-host disease (GVHD) is usually based on quantification
      of rash, serum bilirubin and diarrhea. Standard criteria have been developed and
      used for > 20 years by most transplant centers. However, neither the standard
      GVHD grading system nor any of several revisions has been validated in the
      context of GVHD prophylaxis with cyclosporine. The 1994 Consensus Conference on
      Acute GVHD Grading held in Keystone in January 1994 provided an opportunity to:
      (1) review data regarding these standard criteria; (2) determine if there are
      sufficient data to revise these criteria; and (3) develop recommendations for
      reporting results of GVHD prevention trials. Data were provided for 8249 patients
      from 12 large transplant centers and 2 transplant registries. Standard GVHD
      grading criteria were found to distinguish different mortality risks and
      treatment response rates. Analysis of new data suggested that persistent nausea
      with histologic evidence of GVHD but no diarrhea be included as stage 1
      gastrointestinal GVHD. Additional studies were recommended to evaluate
      heterogeneity of outcome within GVHD grades prior to making further revisions. To
      improve comparability between publications, reports of GVHD prevention trials
      should include an accurate description of the grading system used and should
      report actuarial rates of grades II-IV and III-IV GVHD corrected for graft
      failure and potential interventions for early relapse. Additional information
      should include indications for therapy of GVHD and response.

PMID- 7581075
TI  - Recombinant alpha-interferon as treatment for chronic myelogenous leukemia in
      relapse after allogeneic bone marrow transplantation: a report from the Societe
      Francaise de Greffe de Moelle.
AB  - Thirty three patients with Philadelphia chromosome positive (Ph+) chronic
      myelogenous leukemia (CML) in relapse after allogenic bone marrow transplantation
      (BMT) were treated with recombinant alpha-interferon (IFN). Ten patients received
      IFN for cytogenetic relapse (group I) and 23 (group II) for hematologic relapse.
      The starting dose of IFN varied from 1.7 to 6 million units/m2/day (median 3 x
      10(6) U/m2/day). Among the 10 group I patients, 3 subsequently developed
      hematologic relapse. Of the other 7, a cytogenetic response was observed in 6
      (complete 4, minor 2). Three of these responders are alive in complete
      cytogenetic remission. Of the 23 group II patients, 3 did not respond to IFN but
      20 achieved a complete (CHR) (n = 14) or a partial hematologic response (PHR) (n
      = 6). Thirteen of the 14 CHR patients subsequently achieved a cytogenetic
      response (complete 7, minor 6). Seven of the latter 13 patients are still alive
      in complete cytogenetic remission (CCR). Thus, for the entire group of 33
      patients, IFN was followed by CCR in 11 cases (33%); all these patients are still
      alive and the median follow-up in CCR is now 60.7 months (range 35.3-72.5
      months). The BCR-ABL rearrangement was not detected by RT-PCR in 5 of the 10
      patients analyzed. Eleven other patients developed either blast crisis or
      acceleration. The 3-year probability of survival from the start of IFN therapy
      probability of survival from the start of IFN therapy was 70 +/- 16% (95% CI) and
      was statistically higher for patients who achieved CCR than for the
      others.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581077
TI  - Psychological effects of bone marrow transplantation on children and adolescents:
      preliminary report of a longitudinal study.
AB  - The number of pediatric bone marrow transplantation (BMT) survivors is growing
      rapidly, yet little is known about the long-term neuropsychologic and
      psychosocial sequelae of this procedure. Using a prospective, longitudinal
      design, 64 pediatric patients undergoing BMT were evaluated with standardized
      measures of global intelligence, academic achievement and selected tests of
      neuropsychologic function. In addition, adjustment was assessed with parent and
      patient report measures of social competence, behavior problems and self-esteem.
      Patients were evaluated prior to admission for BMT, and again in the period 6-12
      months after BMT. Longitudinal findings are reported on an initial cohort of 25
      survivors. Cognitive and neuropsychologic function remained stable during the
      study period. The few significant changes from baseline which were observed were
      in the direction of improvement, and may be attributed to practice effects. In
      contrast, declines were observed in patient social competence, self-esteem and
      general emotional well-being. BMT conditioning regimens appear not to be
      associated with significant neuropsychologic impairment in the first year after
      transplant. However, a longer period of follow-up is necessary before
      neuropsychologic late-effects can be ruled out. The first year after BMT is
      characterized by significant psychosocial difficulties for survivors. Adjustment
      issues may provide a more salient focus of study during this time frame.

PMID- 7581079
TI  - Relevance of 10 Caucasian HLA haplotypes in searches for unrelated bone marrow
      donors for 100 patients from a single center.
AB  - Unrelated donor searches for 100 Caucasian patients were referred to France
      Greffe de Moelle Registry (FGM) from September 1987 (24,600 donors) to December
      1993 (71,500 donors, 61% DR typed). After DR typing of HLA-A,B matched donors,
      unsuccessful searches were extended to other European Registries for 36 patients.
      Twenty two patients had a donor (FGM: 19, other Registries: 3) selected on: (1)
      HLA-A,B and DRB,DQB1 split identity; and (2) unidirectional relative response <
      5% in MLR performed twice. Estimated probability of finding a compatible donor at
      9 months in FGM was 12% (s.e. +/- 4%) and 25% at 2 years (s.e. +/- 6%). This
      probability was stringently dependent on a phenoidentity to one very common HLA
      A,B,DR or B,DR haplotype (25% at 9 months when present, representing 19 of 19
      patients with a compatible donor). Without this phenoidentity, the probability
      was zero per cent (P = 0.0001) in FGM searches and < 4% (n = 1) in extended
      searches. The MLR test was shown to be insensitive for screening for DPB1
      mismatches. Clinical status influenced the probability of finding a compatible
      donor at one year ranging from 9% +/- 9% for ALL to 23% +/- 8% for CML (NS).
      Disregarding DPB1 mismatches is the most efficient way of increasing search
      efficiency.

PMID- 7581078
TI  - Physical and psychosocial status of adults one-year after bone marrow
      transplantation: a prospective study.
AB  - Assessment of the impact of bone marrow transplantation (BMT) on long-term
      physical and psychosocial functioning has been hampered by a paucity of
      prospective research. While evidence suggests that many adult BMT recipients
      experience deficits in physical and psychosocial functioning > or = 1 year
      following BMT, whether these deficits existed prior to BMT is not known. Observed
      post-BMT deficits could be attributable to conventional treatments received prior
      to BMT and thus could have antedated BMT. The physical and psychosocial status of
      28 adult BMT recipients was assessed prior to BMT and 12-16 months after BMT.
      Analysis of group means indicated few significant differences between pre- and
      post-BMT assessments. However, inspection of residual change scores suggested
      that physical and psychosocial status improved following BMT for some
      individuals, while that of others declined. Analysis of residual change scores
      indicated that males and older patients at time of BMT reported the largest
      declines in physical and psychosocial status. Longer follow-up is necessary to
      determine whether decrements observed 12-16 months after BMT reflect a slower
      process of post-BMT recovery or whether they constitute fairly permanent
      deficits.

PMID- 7581080
TI  - Relationship between donor-recipient blood group incompatibility and serum
      bilirubin after allogeneic bone marrow transplantation from HLA-identical
      siblings.
AB  - Data on 477 patients with hematologic malignancies undergoing allogeneic bone
      marrow transplantation from HLA-identical siblings were analyzed for correlation
      between donor-recipient ABO blood group incompatibility and the development of
      elevated bilirubin levels (over 17 mmol/l) after transplantation. The median
      bilirubin on day 15 after transplant and the maximum bilirubin in the first 100
      days were significantly higher in 155 patients with ABO-mismatched donors
      compared with 322 patients with ABO-matched donors. In univariate analysis, age >
      16 years (P = 0.000006), ABO incompatibility (P = 0.0004), a conditioning regimen
      other than cyclophosphamide-total body irradiation (P = 0.0005) and a diagnosis
      other than acute leukemia (P = 0.01) were associated with a higher probability of
      developing elevated bilirubin. Incidence of clinically diagnosed graft-versus
      host disease (GVHD), and transplant-related mortality, relapse rates and overall
      survival were not influenced by ABO incompatibility. The hyperbilirubinemia was
      therefore unlikely to be the result of an increased incidence of hepatic
      complications such as GVHD or veno-occlusive disease. We suggest that studies on
      serious transplant-related complications such as GVHD and veno-occlusive disease
      which rely on bilirubin values for diagnosis should take donor-recipient ABO
      incompatibility into account.

PMID- 7581081
TI  - Angiotensin converting enzyme inhibitors in bone marrow transplant recipients
      with depressed left ventricular function.
AB  - Pre-existing left ventricular dysfunction in patients undergoing induction
      therapy with cyclophosphamide prior to bone marrow transplantation (BMT) has
      resulted in overt heart failure in a large number of patients. This fact excludes
      the majority of such patients from consideration for BMT at many centers. We
      sought to determine if prophylactic treatment with the angiotensin converting
      enzyme inhibitor enalapril prevents this deterioration in pre-existing left
      ventricular dysfunction. We treated six consecutive patients with initial left
      ventricular ejection fractions (LVEF) by radionuclide gated blood pool imaging
      (RGBP) of < 50% (42 +/- 7%) with enalapril 5 mg orally twice per day started 48 h
      prior to induction therapy and continued throughout the follow-up period. Serial
      RGBP imaging demonstrated an increase in LVEF in all patients to 54 +/- 6% (P <
      0.005). No patient experienced clinical deterioration during a follow-up period
      of 18 +/- 11 months. We conclude that prophylactic treatment with enalapril may
      prevent deterioration in pre-existing mild left ventricular dysfunction during
      BMT.

PMID- 7581082
TI  - Diffuse alveolar haemorrhage associated with microangiopathy after allogeneic
      bone marrow transplantation.
AB  - Microangiopathic disease and diffuse alveolar haemorrhage (DAH) are uncommon
      serious complications of bone marrow transplantation (BMT), but an association
      between these two conditions has not been previously recognised. We report 4
      patients in whom these two complications occurred after allogeneic BMT for
      haematological malignancy. The patients were 16-39 years of age, and received
      transplants for acute myeloid leukemia, chronic myeloid leukemia and non
      Hodgkin's lymphoma (n = 2). Donors were HLA-identical siblings (n = 3), and a
      matched unrelated volunteer. The patient with AML was receiving a second
      transplant for relapse 3 years after her first BMT, and was prepared with
      busulphan and melphalan; other patients received total body irradiation and
      cyclophosphamide. Microangiopathy occurred 20-48 days after BMT, and was
      associated with renal impairment in all cases, and mental confusion in 3.
      Cyclosporin levels were in the toxic range in 2 cases. DAH occurred 18-55 days
      after BMT, in 3 cases 2-7 days after the onset of microangiopathy, but preceding
      it by 14 days in the other case. Patients were treated with fresh frozen plasma,
      plasma exchange, supplemental oxygen and ventilation in 2 cases. Two patients
      died of progressive respiratory failure, while 2 patients recovered with evidence
      of continuing microangiopathic disease, and died of myocardial infarction or
      fungal infection. We report an association between microangiopathic disease and
      DAH in these BMT patients, and suggest that damage to the pulmonary vascular
      endothelium may be the common pathophysiological event, although no specific
      causative factor could be identified.

PMID- 7581083
TI  - Busulfan concentration in relation to permanent alopecia in recipients of bone
      marrow transplants.
AB  - Alopecia is an important long-term complication after bone marrow transplantation
      (BMT). The aim of this study was to analyze the influence of busulfan
      concentration on the development of permanent alopecia. Sixty five patients who
      survived for at least 6 months after BMT were studied. The median follow-up was
      2.1 years (range 0.5-5.7 years). Thirty one patients (47%) had some degree of
      alopecia and 19 of these patients had extensive alopecia. The mean minimum
      busulfan concentration was 656 +/- 222 ng/ml in patients who developed alopecia
      compared with 507 +/- 224 ng/ml in those who did not (P = 0.005). Patients with
      more extensive alopecia had higher busulfan concentrations than patients with
      less significant abnormalities. In multivariate analysis, alopecia was associated
      with busulfan concentrations higher than the median (OR 3.43; 95% CI 3.04-3.88),
      allogeneic transplantation (OR 2.56; 95% CI 2.28-2.88) and female sex (OR 1.96;
      95% CI 1.73-2.88). There was no association between alopecia and chronic graft
      versus-host disease. High busulfan concentrations may contribute to the
      development of permanent alopecia and the risk for alopecia should be considered
      when choosing the conditioning regimen before BMT.

PMID- 7581086
TI  - FK506 treatment of graft-versus-host disease developing or exacerbating during
      prophylaxis and therapy with cyclosporin and/or other immunosuppressants.
      Japanese FK506 BMT Study Group.
AB  - A phase II study of the efficacy and safety of FK506, a new potent
      immunosuppressant, has been conducted in 49 patients with GVHD after allogeneic
      BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the
      study. FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg
      orally twice a day to those whose GVHD had become uncontrollable with cyclosporin
      and/or other immunosuppressants. The response to FK506 was evaluated in 13
      patients with acute and 26 with chronic GVHD. A marked response was observed in 5
      and a good response in 2 of 13 patients with acute GVHD. For those with chronic
      GVHD, the response was marked in 2 patients, good in 10 and poor in 8. The most
      common adverse effects were renal toxicity (53.1%), followed by nausea and
      vomiting (30.6%) and a feeding of warmth (18.4%). There was a correlation between
      renal toxicity and whole blood levels of FK506. The dose should be adjusted to
      keep a trough level between 15 and 25 ng/ml. FK506 is promising in the treatment
      of both acute and chronic GVHD, even if it is intractable with other
      immunosuppressants, and may be most effective if administered early in the course
      of GVHD.

PMID- 7581087
TI  - Treatment of steroid-resistant graft-versus-host disease after allogeneic bone
      marrow transplantation with anti-CD3/TCR monoclonal antibodies.
AB  - Acute graft-versus host disease (GVHD), one of the major complications of
      allogeneic bone marrow transplantation (BMT), occurs in 30-50% of all patients
      transplanted from HLA-identical sibling donors and in 50-80% of all patients
      transplanted from an unrelated or HLA-mismatched family donor, despite GVHD
      prophylaxis with methotrexate and cyclosporin. We report our experience with
      OKT3/BMA031 treatment in 14 patients with severe steroid-resistant GVHD following
      allogeneic BMT. Three of 5 patients treated in the early post-transplant period
      with OKT3 remitted and 2 of 3 became long-term survivors. Two patients treated
      for extensive chronic GVHD showed only minor responses. Five of 7 patients
      treated with BMA031 showed a partial remission; no complete remission was seen
      after treatment with this antibody. Shortly after the introduction of OKT3 or
      BMA031 therapy a rapid decline of the lymphocyte count, especially the CD3+
      subset, was observed coinciding with a relative increase of CD56+ lymphocytes and
      of gamma/delta TCR+ T cells. Increasing numbers of CD3+ lymphocytes preceded
      recurrence of acute GVHD in three patients. In contrast, persisting CD3
      lymphocytopenia was associated with complete clearance of acute GVHD. The
      incidence of infectious complications following OKT3 or BMA031 therapy was high
      (42%). Thus, to improve treatment results of severe acute GVHD, prophylactic or
      pre-emptive strategies are required to reduce the rate of fatal viral and fungal
      infections.

PMID- 7581085
TI  - Functional hyperactivity of monocytes after bone marrow transplantation: possible
      relevance for the development of post-transplant complications or relapse.
AB  - Bone marrow transplant (BMT) complications such as graft-versus-host disease
      (GVHD), veno-occlusive disease (VOD) and cytomegalovirus (CMV) infection are
      associated with high levels of circulating tumour necrosis factor-alpha (TNF),
      much of which may be monocyte derived. We therefore studied monocyte activation
      after BMT in 36 patients (18 allografts and 18 autografts); plasma neopterin and
      in vitro secretion of superoxide, neopterin and TNF by peripheral blood monocytes
      were assessed. Monocyte respiratory burst was raised at regeneration but returned
      to near-normal within 7 days. Plasma neopterin, and in vitro secretion of
      neopterin and TNF, were greater than twice normal at regeneration and remained
      raised for up to 6 weeks after BMT. Plasma neopterin was higher following
      allogeneic BMT than autologous BMT and was independent of GVHD or VOD. Low levels
      were seen in one patient who failed to engraft. There is evidence of increased
      activation of monocytes at the time of and for several weeks after engraftment
      post-BMT. Abnormal monocyte activation may predispose to, rather than result
      from, the development of complications in the early post-transplant period.

PMID- 7581084
TI  - Hyperinsulinemia in children and adolescents after bone marrow transplantation.
AB  - We report 34 patients (aged 5-18 years) with acute (n = 26) or chronic (n = 1)
      leukemia, non-Hodgkin's lymphoma (n = 3) or severe aplastic anemia (n = 4)
      evaluated for pancreatic beta-cell function 9 months to 10.2 years after
      autologous (n = 19) or allogeneic (n = 15) BMT. Before BMT, all patients received
      cytotoxic drugs, combined with total body irradiation (TBI) in 24 cases or
      thoracoabdominal irradiation (TAI) in 4 children. Patients were investigated for
      fasting blood glucose (FBG), HbA1C, anti-insulin (IAA) and islet cell antibodies
      (ICA), first-phase insulin response (FPIR) and insulinemia/glycemia (I/G) ratio
      on i.v. glucose tolerance test (GTT) and C-peptide response after glucagon 1 mg
      i.v. Results were compared with those obtained in 21 age- and sex-matched
      controls. None of the patients or controls had IAA and/or ICA. FBG and HbA1C were
      normal in all children. In the patients, glycemia on i.v. GTT was similar to
      controls whereas insulin levels I/G ratio and FPIR were significantly higher in
      patients than in controls, as well as C-peptide levels. We divided the patients
      on the basis of the radiotherapy into group I with TBI (n = 18), group II with
      TAI (n = 4) and group III who were not irradiated (n = 4). The I/G ratio, FPIR on
      i.v. GTT and C-peptide response were significantly higher in group I compared
      with the other two groups and controls. The increased insulin and C-peptide
      levels in our patients with normal glycemia might be interpreted as a state of
      insulin resistance, more evident in patients who received TBL.

PMID- 7581088
TI  - FK506 (tacrolimus) in the treatment of steroid-resistant acute graft-versus-host
      disease in children undergoing bone marrow transplantation.
AB  - Steroid-resistant graft-versus-host disease (GVHD) is an often lethal
      complication of bone marrow transplantation (BMT). FK506 (tacrolimus) is a new
      potent immunosuppressant which has been shown to be superior to conventional
      immunosuppression in the prevention and treatment of graft rejection in
      recipients of solid organ transplants. To determine whether FK506 is effective in
      the treatment of steroid-resistant acute GVHD, 6 children with biopsy-proven
      severe GVHD were studied. FK506 was administered as intravenous or oral therapy
      and the dose was adjusted to achieve serum levels between 0.5 and 1.0
      microgram/ml by ELISA. Steroid doses were tapered based on clinical grading in
      each organ. Within 1-2 days, improvement occurred in skin and gut in all
      patients, and in liver in 3 patients. Toxicity attributable to FK506 was similar
      to that described in solid organ transplant patients and included neurotoxicity,
      nephrotoxicity and gastrointestinal effects. While FK506 is effective in the
      treatment of steroid-resistant acute GVHD, toxicity may limit its use. Further
      studies evaluating FK506 as GVHD prophylaxis and treatment of less advanced GVHD
      are needed.

PMID- 7581089
TI  - Time-course of the recovery of cellular immune function after high-dose
      chemotherapy and peripheral blood progenitor cell transplantation for high-grade
      non-Hodgkin's lymphoma.
AB  - Chemotherapy induces high remission rates in high-grade lymphoma. However relapse
      remains a major problem. One approach to this is myeloablative chemotherapy with
      transplantation of autologous bone marrow or peripheral blood progenitor cells
      (PBPC). Immunological mechanisms have been suggested to play a role in the
      prevention of relapse after transplantation. We investigated the recovery of
      cellular immune functions after high-dose chemotherapy and PBPC transplantation
      in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid
      reconstitution of natural killer (NK) and inducible lymphokine-activated killer
      (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher
      levels of LAK-generation in the post-transplant period compared with levels prior
      to myeloablative treatment. Absolute lymphocyte counts in peripheral blood
      reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells
      and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient
      increase in CD56+ and CD16+ cell counts post-transplant. No change in the
      proportion of CD25+ cells was noted. These results show that PBPC transplantation
      leads to a rapid recovery of cellular immune functions after myeloablative
      chemotherapy and provides evidence for an increased presence of LAK precursor
      cells early in the post-transplant period which can be activated by IL-2 to exert
      high levels of cytotoxicity.

PMID- 7581090
TI  - Influence of total nucleated cell dose from marrow harvests on outcome in
      patients with acute myelogenous leukemia undergoing autologous transplantation.
AB  - This retrospective study was conducted to determine whether the total number of
      nucleated cells (TNC)/kg collected at marrow harvest was associated with outcome
      in 151 patients with acute myelogenous leukemia (AML) who received an autologous
      purged (n = 67) or non-purged (n = 84) marrow transplant. At the time of
      transplant 33 patients were in first complete remission (CR), 47 in second CR, 54
      in first relapse and 17 beyond second CR. Ninety patients received busulfan (BU)
      16 mg/kg and cyclophosphamide (CY) 120 or 200 mg/kg, 51 patients received CY 120
      mg/kg and total body irradiation (TBI) 12-15.75 Gy and 10 patients received BU 8
      mg/kg, CY 60 mg/kg and TBI 12 Gy as conditioning regimens. Patients whose marrow
      harvest yielded < 2 x 10(8) TNC/kg did not undergo purging with 4
      hydroperoxycyclophosphamide (4HC). This group of patients (n = 28) had a 100 day
      mortality of 50% and only 54% achieved a granulocyte levels of > 0.5 x 10(9)/l
      and 29% achieved platelet transfusion independence. Patients whose marrow harvest
      yielded 2-4 x 10(8) TNC/kg and did not undergo marrow purging had a 20% mortality
      by day 100, 91% recovered granulocytes to > 0.5 x 10(9)/l and 61% became platelet
      independent. Patients whose marrow harvest yielded 2-4 x 10(8) TNC/kg and
      underwent marrow purging with 4HC had a 50% mortality by day 100 and 58% achieved
      a granulocyte levels of > 0.5 x 10(9)/l and 42% became platelet transfusion
      independent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581091
TI  - Rapid engraftment after autologous transplantation utilizing marrow and
      recombinant granulocyte colony-stimulating factor-mobilized peripheral blood stem
      cells in patients with acute myelogenous leukemia.
AB  - This study was performed to determine whether peripheral blood stem cells (PBSCs)
      mobilized with recombinant granulocyte-colony stimulating factor (rhG-CSF)
      increase the tempo of granulocyte and platelet recovery when added to marrow in
      patients with acute myelogenous leukemia (AML) undergoing autologous bone marrow
      transplantation (BMT). Twenty six patients with AML had bone marrow harvested in
      first (n = 16) or second (n = 10) complete remission (CR) and cryopreserved.
      Patients received rhG-CSF alone (n = 20) or rhG-CSF following chemotherapy (n =
      6). PBSCs were collected from 24 of the 26 patients a median of 7 (range 3-2130)
      days after marrow harvest. Two patients presumed to be in second CR did not have
      PBSCs collected because of early relapse. Fourteen patients in first CR (n = 3),
      second CR (n = 8) or first relapse (n = 3) proceeded to autologous BMT utilizing
      marrow + rhG-CSF-mobilized PBSCs. Engraftment parameters were compared with a
      historical group of 158 patients with AML who had received purged (n = 67) or
      unpurged (n = 91) autologous BMT without PBSCs. The median number of peripheral
      blood total nucleated and CD34+ cells collected from 24 patients was 19.55 x
      10(8)/kg (range 1.83-54.83) and 5.59 x 10(6)/kg (1.23-34.79), respectively. All
      patients transplanted achieved a granulocyte level of > 0.5 x 10(9)/l with a
      median of 13 days (range 11-27 days) and platelets to 20 x 10(9)/l median 14 days
      (range 9-83 days).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581092
TI  - Source of stem cells impacts on hematopoietic recovery after high-dose
      chemotherapy.
AB  - The restoration of hematopoiesis after high-dose chemotherapy may be accelerated
      by the use of stem cells from the bone marrow (BM) or peripheral blood. Numerous
      reports utilizing mobilized peripheral blood progenitor cells (PBPC) for stem
      cell rescue have shown that PBPC are sufficient to restore hematopoiesis, but
      there are little data comparing the recovery among patients treated with various
      stem cell sources. We reviewed the clinical outcomes of 69 women at our
      institution who were treated for locally advanced or metastatic breast cancer
      with high-dose cyclophosphamide (CY) and thiotepa and autologous stem cell and
      growth factor support. Of the 43 patients with normal BM, 19 received BM alone
      and 24 received BM plus G-CSF mobilized PBPC. Of the 26 patients with evidence of
      metastatic disease in the BM, or evidence of fibrosis and hypocellularity, 15
      received CY-mobilized PBPC and 11 received CY/G-CSF-mobilized PBPC. Of the marrow
      negative patients, those receiving BM alone had significantly longer (P < 0.001)
      granulocyte recovery (absolute neutrophil count > 500 x 10(6)/l) and platelet
      recovery (platelets > 50 x 10(9)/l) compared with BM + G-CSF-mobilized PBPC. They
      also had significantly longer (P < 0.001) durations of antibiotic and
      amphotericin usage, increased transfusion requirements and longer
      hospitalizations. Of the marrow-positive patients, there was a slightly shortened
      granulocyte recovery, shortened hospital stays and lessened amphotericin usage in
      the patients who received CY/G-CSF-mobilized PBPC compared with the CY-mobilized
      patients. Although the number of harvested mononuclear cells differed
      significantly between the groups, this did not correlate with the time to
      hematopoietic recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581093
TI  - Immunocytochemical detection of tumor cells in bone marrow and peripheral blood
      stem cell collections from patients with ovarian cancer.
AB  - High-dose chemotherapy (HDC) followed by autologous hematopoietic reconstitution
      is an experimental treatment option for patients with epithelial ovarian cancer.
      However, the incidence of occult ovarian tumor cell involvement in autologous
      bone marrow (BM) or peripheral blood stem cell (PBSC) autografts has not been
      widely investigated. We used a highly sensitive immunocytochemical (ICC)
      procedure that detects occult blood-borne tumor micrometastases. We analyzed 24
      BM specimens (15 obtained during therapy and 9 harvest samples) and seven PBSC
      specimens from 22 patients with ovarian cancer. Overall, ICC analysis detected
      immunostained tumor cells in 10 of 23 evaluable BM specimens (43%) from 9 of 19
      patients (47%). One of 9 (11%) harvest samples contained tumor cells. Only one of
      the 10 ICC-positive BM specimens had tumor cells detected by routine
      histopathological analysis. ICC-detectable tumor cells were cleared from the
      marrow of two patients during chemotherapy. None of the seven PBSC specimens
      contained tumor cells. We conclude that ovarian cancer micrometastases have the
      potential to contaminate BM, as is also the case in patients with other
      epithelial malignancies. In the limited number of specimens analyzed, PBSC
      harvests appeared to provide a less tumor-contaminated source of hematopoietic
      stem cells for autologous transplantation.

PMID- 7581094
TI  - Phase I multicenter trial of interleukin 6 therapy after autologous bone marrow
      transplantation in advanced breast cancer.
AB  - Our purpose was to determine the maximum tolerated dosage of rhIL-6 after high
      dose cytotoxic chemotherapy and autologous BMT in patients with advanced breast
      cancer. Twenty patients (median age 43.5 years) received either CY and thiotepa
      (n = 3) or CY, thiotepa and carboplatin (n = 17) for 4 days. Unpurged autologous
      BM was reinfused 72 h later. Daily rhIL-6 therapy began the day of marrow
      infusion and continued until recovery of neutrophils (> or = 1.5 x 10(9)/l) and
      platelets (> or = 50 x 10(9)/l) or for a maximum of 28 days at a dosage of 0.3
      microgram/kg/day (n = 7), 1 microgram/kg/day (n = 6) or 3 micrograms/kg/day (n =
      7). Two of the initial 4 patients given rhIL-6 at 0.3 mu/kg i.v. experienced
      grade 4 hyperbilirubinemia, so subsequent patients received s.c. rhIL-6. Most
      toxicities attributable to rhIL-6 were reversible or mild constitutional
      symptoms, but dose-limiting grade 4 hyperbilirubinemia also occurred in 3 of the
      7 patients receiving the 3 micrograms/kg dose. At the 0.3 and 1 microgram/kg/day
      doses, 8 of 13 patients completed the study vs. only 2 of 7 at the 3
      micrograms/kg/day dose. During rhIL-6 treatment, neutrophil recovery (> or = 500
      x 10(6)/l) occurred in 12 patients and platelet recovery (> or = 20 x 10(9)/l)
      occurred in 6 patients, 5 of whom received the 0.3 or 1 microgram/kg/day s.c.
      dose. The maximal tolerated dose of rhIL-6 after autologous BMT appeared to be 1
      microgram/kg/day s.c., a dose appreciably lower than the maximal tolerated dose
      after conventional cytotoxic therapy.

PMID- 7581095
TI  - Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia
      in second remission: factors predictive of survival, relapse and graft-versus
      host disease.
AB  - Between 1983 and 1993, 42 patients with acute lymphoblastic leukemia (ALL) in
      second complete remission (CR) underwent an allogeneic HLA-identical bone marrow
      transplant (BMT; there was one family mismatched graft). The conditioning
      regimens varied, consisting of cyclophosphamide (CY) and total body irradiation
      (TBI; n = 10); CY, TBI, Ara C, VP-16 (n = 11); TBI, Ara C, melphalan (n = 20)
      (TAM) or other (n = 1). Cyclosporine A (CsA) (n = 15) or CsA and methotrexate
      (MTX) (n = 24) were the main regimens for prophylaxis of graft-versus-host
      disease (GVHD). Nineteen of 42 patients are alive in CR ranging from 1 to 72
      months after BMT with a median follow-up of 36 months. The 4-year actuarial
      survival rate was 53%. The actuarial relapse rate was 17%. Twenty three patients
      died: 4 patients of leukemic relapse, 9 of infection, 2 of acute GVHD, 2 of
      multiorgan failure after chronic GVHD, 2 of a secondary tumour and 4 patients
      died of other causes. Several pre- and post-transplant characteristics were
      analyzed to determine predictive factors for survival, relapse and GVHD. The
      relapse rate was significantly influenced by the type of conditioning regimen
      with no relapse in the TBI, Ara C, melphalan group. The analysis of long-term
      sequelae shows that there are no severe complications in this last group. Our
      results confirm that allogeneic BMT can lead to long-term survival for children
      with ALL in second CR and suggest an advantage of using the TAM conditioning
      regimen in the eradication of the leukemic disease.

PMID- 7581096
TI  - Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following
      allogeneic bone marrow transplantation.
AB  - Preliminary studies in allogeneic BMT suggest that recombinant human granulocyte
      macrophage colony-stimulating factor (rhGM-CSF) is well tolerated. This is a
      prospective, multicenter, randomized, double-blind, placebo-controlled trial.
      Yeast-derived rhGM-CSF 250 micrograms/m2/day or placebo was administered by 4
      hour i.v. infusion starting on the day of marrow infusion (day 0) to day 20. All
      patients received HLA-identical sibling marrow and cyclosporine and prednisone
      for GVHD prophylaxis. Fifty three patients received rhGM-CSF and 56 received
      placebo. Comparison of demographics revealed no differences. The time to achieve
      an absolute neutrophil count of > 0.5 x 10(9) cells/l was shortened in rhGM-CSF
      treated patients (day 13 vs. 17, P = 0.0001). The incidences of grade III-IV
      mucositis and infection were significantly reduced (P = 0.005, P = 0.001,
      respectively) and duration of hospitalization was modestly shortened by 1 day (P
      = 0.02) in rhGM-CSF treated patients. No differences in platelet recovery,
      erythrocyte recovery, incidence of veno-occlusive disease, GVHD severity, relapse
      or survival were observed. In conclusion, rhGM-CSF is well tolerated and reduces
      post-transplant morbidity in patients undergoing HLA-identical allogeneic BMT.

PMID- 7581097
TI  - Serum granulocyte colony-stimulating factor (G-CSF) levels after allogeneic T
      cell-depleted marrow transplantation.
AB  - Endogenously produced and exogenously administered granulocyte colony-stimulating
      factor (G-CSF) has correlated with myeloid engraftment in a number of
      hematopoietic progenitor cell transplantation settings. Given the increased
      susceptibility of T cell-depleted (TCD) bone marrow transplants (BMT) to graft
      failure, a cohort of 36 (21 male and 15 female) recipients of TCD BMT was
      evaluated prospectively during the first month post-transplant for circulating
      serum G-CSF levels, to examine the correlation between myeloid engraftment and G
      CSF levels. All recipients of TCD BM had measurable G-CSF levels, with a median
      peak level of 1750 pg/ml (range 540-26,250 pg/ml) occurring at a median of 5 days
      (range 1-18 days) after BM infusion. There was no association between G-CSF
      kinetics within 1 month post-transplant and the development of primary non
      engraftment or secondary graft failure. One patient with primary non-engraftment
      and 6 patients with secondary graft failure exhibited median G-CSF peak levels of
      1600 pg/ml and 1850 pg/ml (range 600-16,250 pg/ml) occurring 5 and 5.5 days
      (range 4-7 days) after BM infusion, respectively. Additionally, the patient with
      primary non-engraftment demonstrated a high G-CSF level in response to a low
      absolute neutrophil count (ANC). An inverse relationship between serial G-CSF
      levels and concomitant ANC was documented (log G-CSF = 6.19-0.009 ANC, P <
      0.001). Higher peak G-CSF levels were associated with older recipient age (P =
      0.01) and lower BM cell dose (P = 0.02), while administration of anti-thymocyte
      globulin post-transplant did not alter G-CSF levels.

PMID- 7581099
TI  - Mixed chimerism following bone marrow transplantation for severe combined
      immunodeficiency: a study by DNA fingerprinting and simultaneous
      immunophenotyping and fluorescence in situ hybridisation.
AB  - We report a girl with severe combined immunodeficiency (SCID) who had a paternal
      T-depleted bone marrow transplant (BMT) when 11 months old. Engraftment was
      documented but karyotyping of marrow cells 1 year after BMT showed recipient
      metaphases (XX) only. However, she remained clinically well and further analysis
      y karyotyping of PHA-cultured peripheral blood mononuclear cells (PBMC) showed
      donor metaphases (XY) only. DNA fingerprinting confirmed mixed chimerism in the
      peripheral blood. The granulocytes were of recipient origin and the PBMC of mixed
      origin, the donor proportion of which increased after culture with PHA. Using
      simultaneous immunophenotyping and fluorescence in situ hybridisation (FISH) with
      chromosomes X and Y-specific probes, circulating T cells were demonstrated to be
      of donor origin whereas B cells and myeloid cells were mostly of recipient
      origin.

PMID- 7581098
TI  - Comparison of autologous bone marrow transplantation and peripheral blood stem
      cell transplantation after first remission induction treatment in multiple
      myeloma.
AB  - The optimal source of stem cells is a controversial issue in the field of
      autologous stem cell transplantation. A comparison of autologous bone marrow
      transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT)
      after first remission induction treatment in multiple myeloma was made by a
      retrospective analysis of 132 transplants performed in 18 French Centers from
      1984 to 1991 (81 autologous BMT, 51 PBSCT). The two groups differed in the median
      age (PBSCT 49 years; autologous BMT 55 years, P < 0.001), the duration of
      chemotherapy prior to transplantation, the interval between stem cell collection
      and transplantation, and in the conditioning regimen (more total body irradiation
      and higher doses of irradiation in the PBSCT group). The median time to
      neutrophil recovery was shorter in the PBSCT group (13 days vs. 20 days, P <
      0.001), but the median time to platelet recovery did not differ significantly
      between PBSCT (26 days) and autologous BMT (22 days). There was no significant
      difference between the two groups regarding overall response rate (PBSCT 84%,
      autologous BMT 82%) and complete remission rate (PBSCT 37%, autologous BMT 36%).
      The actuarial relapse-free survival, time to treatment failure and overall
      survival were not significantly different. A case controlled study comparing 43
      autologous BMT and 43 PBSCT matched for age and status at the time of
      transplantation did not show any advantage of PBSCT over autologous BMT in terms
      of immediate outcome, relapse-free survival, overall survival and time to
      treatment failure. Thus, in this retrospective analysis, the only significant
      benefit for PBSCT was reduced time to neutrophil recovery.

PMID- 7581101
TI  - Immunotherapy with donor leukocyte infusions for patients with relapsed acute
      myeloid leukemia following partially mismatched related donor bone marrow
      transplantation.
AB  - Donor leukocyte infusions (DLI) were used to treat 2 patients with AML who
      relapsed within 4 months of treatment with partially mismatched related donor
      (PMRD) BMT representing 1-2 HLA-mismatches. No other form of cytoreductive
      therapy was given to these patients. Both patients developed GVHD (grade II-III)
      following DLI requiring steroid therapy. One of these patients went into complete
      remission following development of GVHD and immunophenotypic analysis of
      peripheral blood showed increased numbers of CD3+/CD8+ T cells, CD56+/CD8+
      lymphokine activated killer (LAK) cells and CD16+/CD56+ natural killer (NK) cells
      expressing intermediate affinity IL-2 receptor P75. Unfortunately, the response
      was of short duration and the patient relapsed 8 weeks later ultimately resulting
      in death. The second patient did not show any response to DLI and died of
      progressive leukemia in conjunction with active GVHD. We conclude that DLI from
      PMRD carries a high risk for the development of GVHD and may have an anti
      leukemia effect for relapsed AML. The anti-leukemic effect from PMRD DLI may be
      mediated by cytotoxic T lymphocytes, LAK cells and NK cells.

PMID- 7581100
TI  - Low CD4 lymphocyte count in a patient with P. carinii pneumonia after autologous
      bone marrow transplantation.
AB  - Authors report a case of P. carinii pneumonia in a child with 5% CD4 lymphocytes
      (absolute number 5/microliters) after autologous bone marrow transplantation
      followed by pulmonary irradiation. Serial evaluation of CD4 lymphocyte count or
      percentage or, at least, detection of significant and persistent lymphopenia
      could be useful for detecting a high risk of developing P. carinii pneumonia.

PMID- 7581102
TI  - Reactivation toxoplasmic retinochoroiditis in patients undergoing bone marrow
      transplantation: is there a role for chemoprophylaxis?
AB  - The objective of this study was to report the occurrence of reactivation ocular
      toxoplasmosis in bone marrow transplant (BMT) recipients and to propose
      guidelines for identification and chemoprophylaxis of high-risk patients. The
      study design was a series of cases from the tertiary care university hospital
      which has an active BMT program. The patients were two recipients of autologous
      BMTs with past histories of toxoplasma retinochoroiditis who developed
      symptomatic reactivation of ocular toxoplasmosis as documented by formal
      opthalmologic examination in the early post-transplant period. Opthalmoscopic
      examinations in the two patients with non-Hodgkin's lymphoma who received
      autologous transplants and then developed decreased visual acuity in the first
      week after transplant revealed recurrent retinochoroiditis adjacent to old
      toxoplasma lesions. Pre-transplant eye examinations in both patients had
      demonstrated only inactive chorioretinal scars. Therapy with sulfadiazine,
      pyrimethamine and prednisone ultimately led to resolution of retinitis in both
      patients. BMT recipients who are seropositive for antibody to T. gondii and have
      findings consistent with previous toxoplasma retinochoroiditis on pre-transplant
      ophthalmologic examination appear to be at risk for reactivation of ocular
      toxoplasmosis in the early post-transplant period and may warrant preventive
      chemoprophylaxis for toxoplasmosis.

PMID- 7581103
TI  - Extrapyramidal symptoms in a BMT recipient with hyperintense basal ganglia and
      elevated manganese.
AB  - Neurologic syndromes attributed to conditioning or medications have been reported
      in BMT recipients. A patient is presented who developed extrapyramidal symptoms
      on day +56 after allogeneic BMT. Brain magnetic resonance images of this patient
      demonstrated hyperintense basal ganglia, which has been associated with manganese
      (Mn) toxicity. The patient had received total parenteral nutrition (TPN) with
      standard trace element supplementation and had been cholestatic. Serum Mn was
      elevated, and continued to be so 5 months after BMT, long after discontinuation
      of TPN. Cholestatic patients and those on long-term TPN have been found to have
      high blood or serum levels of Mn, but generally are asymptomatic. When other
      cholestatic BMT patients were reviewed, all had elevated serum Mn. Manganese
      supplementation in TPN requires evaluation for BMT recipients.

PMID- 7581105
TI  - Epiglottitis following preparation for allogeneic bone marrow transplantation.
AB  - We describe a 7-year-old boy who developed acute, airway-threatening, non
      infectious epiglottitis following high-dose cytosine arabinoside and total body
      irradiation preparative regimen for allogeneic BMT. Unlike gastrointestinal
      symptoms and oropharyngeal mucositis, acute epiglottitis is a previously
      unreported early complication following allogeneic BMT preparation. The
      pathogenesis of epiglottitis in our patient was presumably multifactorial,
      resulting from the combination of chemotherapy and irradiation. We recommend that
      this diagnosis be considered in the differential diagnosis of patients with
      significant upper airway symptoms following BMT preparation.

PMID- 7581104
TI  - Rapid development of disseminated superficial porokeratosis after transplant
      induction therapy.
AB  - Disseminated superficial actinic porokeratosis (DSAP) is a cutaneous disorder,
      usually inherited in an autosomal dominant fashion, characterized by numerous
      annular papules with subtle raised hyperkeratotic borders and slightly atrophic
      centers. While the precise pathophysiologic mechanisms underlying the development
      of DSAP are unknown, one hypothesis is multifocal expansion of atypical clones of
      keratinocytes, perhaps unmasked by actinic damage, as implied by its name.
      Although primarily of cosmetic concern, there is an increased risk of squamous
      cell carcinoma of the skin developing within DSAP lesions, which often show
      histologic keratinocytic atypia centrally. Immunosuppression, which is a
      significant risk factor for secondary malignancies including cutaneous squamous
      cell carcinoma, is also a well-documented precipitant of porokeratosis. We report
      a 62-year-old man who developed DSAP in a widely and rapidly progressive manner
      within days of receiving total body radiation and high-dose induction
      chemotherapy as planned preparative therapy for an autologous peripheral blood
      stem cell transplant for relapsed high grade lymphoma. Our patient's eruption of
      DSAP highlights a little recognized cutaneous manifestation of aggressive bone
      marrow transplant induction therapy.

PMID- 7581107
TI  - Bone marrow transplantation for multiple sclerosis.
AB  - Multiple sclerosis is the most common demyelinating neurologic disease. Animal
      studies from three separate institutions suggest that BMT may be beneficial. Of
      paramount concern is the risk to benefit ratio. However, for patients with
      progressive disease at onset, survival is similar to patients with indolent
      lymphomas; while for patients with malignant MS, survival is roughly equivalent
      to chronic phase CML. In addition, for these patients, life may become
      intolerable due to progressive pain and disability. The fate of such individuals
      may justify, in carefully selected patients and in a controlled investigational
      protocol, the risk of early mortality from BMT.

PMID- 7581109
TI  - Peripheral tolerance to host minor histocompatibility antigens in radiation bone
      marrow chimeras abrogates lethal GVHD while preserving GVL effect.
AB  - We previously reported that Mls-1a B10.D2 donor preimmunization prevents the
      development of a lethal graft-versus-host disease (GVHD) directed against host
      minor histocompatibility antigens (mHAgs) in lethally irradiated (DBA/2 x
      B10.D2)F1 recipients (LS mice). In the same combination, the graft of T-depleted
      bone marrow cells also results in no GVHD (TCD BM mice). Both groups of mice
      exhibit a host specific tolerance. In this paper, we examined whether a graft
      versus-leukemia (GVL) effect can still take place without lethal GVHD in LS and
      TCD BM mice. The i.v. injection of P815 tumor cells into these mice, 2-3 months
      after the graft, indicates an antitumor activity in LS mice but not in TCD BM
      mice. When the P815 cells were administered 1 day before irradiation and graft,
      the leukemic mortality was significantly delayed in mice reconstituted with BM
      and spleen cells from a preimmunized donor, but not in mice reconstituted with T
      cell-depleted BM. In LS mice, a subclinical GVHD develops, probably due to CTL
      alloreactivity against host mHAgs that is observed in vitro. Moreover, cell
      depletion of the donor inoculum before grafting indicates that the antitumor
      effect is exclusively mediated by CD8+ T cells. In summary, a beneficial GVL
      effect, mediated by CD8+ T cells, can be preserved without lethal GVHD.

PMID- 7581108
TI  - Signal transduction by B and T cells early after bone marrow transplantation: B
      cell calcium flux responses are intact whereas lack of CD4 cells accounts for
      impaired T cell responses.
AB  - We previously found that intracellular ionized calcium ([Ca2+]i) flux responses
      after anti-CD3 crosslinking of CD3/TCR on T cells from allogeneic and autologous
      bone marrow transplant (BMT) recipients were impaired, Yamagami et al. J Clin
      Invest 1990; 86: 1347-1351. In contrast to the earlier study, this study focuses
      on identifying the T cell subset(s) responsible for the defects and determining
      if B cell responses are defective in BMT recipients early after BMT. In 37
      recipients after anti-CD3 stimulation of PBL, a mean of 25.9% responding T cells
      was observed. This was significantly lower than the mean of 43.6% responding T
      cells in PBL from 21 normals (P < 0.001). The proportion of responding T cells in
      PBL (T PBL) increased in the recipients with time after BMT. By 6 months after
      BMT, the mean percent of responding T PBL approached the normal range. On the
      other hand, a mean of 8.1% responding B cells in anti-IgM crosslinked PBL from 24
      recipients was not different from the mean of 7.4% responding B cells in anti-IgM
      crosslinked PBL from 16 normals (P = 0.6). Four color flow cytometry was used to
      identify subpopulations of lymphocytes. Enriched B cells were tested by gating
      out CD3+ and CD56+ cells to confirm the results of unfractionated PBL. In 8
      recipients, the mean percent responding B cells was 36.6% and was not different
      from 6 normals (mean = 41.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581106
TI  - Analysis of peripheral blood progenitor cells demonstrates limitations of minimal
      residual disease diagnosis in a case of acute promyelocytic leukemia.
AB  - Detection of minimal residual disease (MRD) by analysis of the PML-RAR alpha
      fusion transcript using the RT-PCR method is routinely carried out on peripheral
      blood and bone marrow of patients with APL (AML, FAB:M3). Therapy aims to achieve
      repeated negative results in these patients thus confirming clinical complete
      remission. We report a case of APL in second complete remission in which no
      leukemic cells had been detected in BM and PB for 20 months, and in which PBPC
      pheresis was carried out for future transplantation. In two of five pheresis PML
      RAR alpha fusion transcripts were detected. This shows that the residual leukemic
      population may only reach detection level after enrichment by PBPC-pheresis.

PMID- 7581110
TI  - Effect of IL-7 or IL-4 on reconstitution of donor lymphoid cells in congenic
      murine bone marrow transplantation.
AB  - IL-7 and IL-4 are known to influence the growth of cells of the lymphoid lineage.
      In this study, we investigated the effects of in vivo administration of IL-7 or
      IL-4 in mice subjected to congenic BM transplant. C57BL/6 Ly5.1+ mice were
      subjected to TBI, followed by transfer of B and T cell-depleted BM from C57BL/6
      Ly5.2+ donor mice. Recipient mice were implanted with 14-day miniosmotic pumps
      that delivered IL-7, IL-4 or PBS and were examined for reconstitution of lymphoid
      cells using flow cytometry on different days. We observed no significant
      difference in the number of splenocytes, thymocytes and PBLs between recipient
      mice administered with cytokines or normal control mice. However, we observed
      that IL-4 infusion resulted in appearance of increased numbers of donor
      CD23+B220+ cells and also donor cells expressing Fc receptors for IgM (Fc micro
      R) and B220. Since CD23 is present only on mature B cells, our data demonstrate
      that following BMT, IL-4 treatment results in the development of more mature B
      cells compared to control mice. Additionally, we observed that IL-7 infusion
      resulted in significantly decreased expression of donor sIgM+B220+ cells.
      However, the effects of IL-7 or IL-4 were observed when the cytokines were
      actively administered and rapidly abated upon cessation of cytokine therapy.

PMID- 7581111
TI  - Multiple minor histocompatibility antigen-specific cytotoxic T lymphocyte clones
      can be generated during graft rejection after HLA-identical bone marrow
      transplantation.
AB  - Graft rejection after T cell-depleted HLA-genotypically identical bone marrow
      transplantation (BMT) is probably mediated by mH antigen-specific cytotoxic T
      lymphocytes (CTL). We have analyzed peripheral blood mononuclear cells (PBMC)
      from a female bone marrow graft recipient, collected during graft rejection after
      a sex mismatched HLA-identical BMT. A CTL line was generated by stimulating
      recipient PBMC collected during graft rejection with donor PBMC and donor EBV
      transformed lymphoblastoid cell lines. From this CTL line a large number of
      clones of different specificity and phenotype was established by limiting
      dilution. These clones exhibited several mH antigen specificities, restricted by
      HLA-B7, -B27 or -DR2 as shown by differential recognition of family members and
      unrelated individuals sharing potential restriction elements. The CD3+CD4+ and
      CD3+CD8+ bulk culture was cloned, resulting in 50 HLA-B7 restricted CD3+CD4
      CD8+CTL clones, three HLA-B27 restricted CD3+CD4-CD8+CTL clones, one HLA-DR2
      restricted CD3+CD4+CD8-CTL clone and two additional HLA class II restricted
      CD3+CD4+CD8-CTL clones with a different specificity. One representative clone of
      each specificity was selected for further analysis. The CTL line and the HLA-B7
      restricted CD8+CTL clone, but not the HLA class II restricted CD4+ CTL clone,
      inhibited the growth of donor hematopoietic progenitor cells (HPC). In
      conclusion, these results show that graft rejection after HLA-identical BMT may
      be mediated by multiple CTL clones that specifically recognize one mH antigen
      peptide presented by different HLA molecules or different mH antigens expressed
      on donor cells and that CTL, but not CD4+ CTL inhibited donor HPC growth.

PMID- 7581113
TI  - Cytokine-mediated immunotherapy with or without donor leukocytes for poor-risk
      acute myeloid leukemia relapsing after allogeneic bone marrow transplantation.
AB  - Six patients with high-risk acute myeloid leukemia (AML) relapsing after
      allogeneic bone marrow transplantation (BMT) were treated with interferon-alpha
      2b to stimulate graft-versus-leukemia reactions. Additionally, donor mononuclear
      cells were infused with or without interleukin-2 as first-line treatment or upon
      failure of interferon-alpha 2b in 5 patients. Two patients developed clinical
      acute graft-versus-host disease (GVHD) after a combination of donor leukocytes
      and interferon-alpha, and one developed de novo chronic GVHD after interleukin-2
      and interferon-alpha. Complete remission was attained in 4 patients whereas 2
      patients showed no response. Two of the responding patients relapsed rapidly.
      Four patients died of a combination of complications of immunotherapy and
      progressive disease. Two patients are alive in remission with chronic GVHD
      (Karnofsky performance scores of 80%) 8 and 18 months after immunotherapy. We
      conclude that cytokine-mediated immunotherapy with or without donor cell
      infusions may be effective in some cases of AML relapsing after allogeneic BMT,
      and may result in long-term survival. With limited data, it appears that
      development of chronic GVHD after immunotherapy is essential for continued
      remission.

PMID- 7581112
TI  - Autologous stem cell transplantation for refractory and relapsed Hodgkin's
      disease: factors predictive of prolonged survival.
AB  - We analyzed patient, disease, and treatment related factors associated with long
      term disease-free survival (DFS) in 62 patients with refractory or recurrent
      Hodgkin's disease treated with high-dose cyclophosphamide (6000 mg/m2),
      carmustine (BCNU; 300 mg/m2), and etoposide (900 mg/m2) (CBV) followed by
      autologous stem cell transplantation. There were no deaths resulting from
      toxicity of the preparative regimen, and all patients survived the peritransplant
      period. At 28 days post-transplant, the complete response (CR) rate was 76%.
      Patients who achieved a CR had a 50% estimated 3-year DFS (95% CI, 35-64%).
      Twenty-three (37%) patients remain in continuous clinical remission 1.3 to 7.7
      years (median 3.8 years) after transplantation. In a univariate analysis, factors
      significantly associated with improved DFS included absence of B symptoms (fever,
      night sweats and unexplained weight loss) at transplant, response to pre
      transplant salvage chemotherapy, less tumor bulk at time of transplant, and fewer
      prior treatment regimens. Stepwise multivariate analysis showed that the absence
      of B symptoms at time of transplant was independently and significantly
      associated with improved DFS after transplantation. CBV with autologous stem cell
      support can produce durable remissions with acceptable toxicity in a substantial
      proportion of patients who are asymptomatic at time of transplant. Earlier
      application of transplantation or development of additional effective
      antineoplastic modalities will be required to improve the results of
      transplantation for patients with advanced Hodgkin's disease.

PMID- 7581114
TI  - Liver T cell subsets and adhesion molecules in murine graft-versus-host disease.
AB  - Murine GVHD across multiple minor histocompatibility barriers (B10.D2 into
      irradiated BALB/c) results in cell-mediated destruction of bile ducts inside the
      liver. Similar changes are characteristic of hepatic GVHD in humans following
      BMT. We have defined the phenotypes of inflammatory cells and the
      accessory/adhesion molecules expressed in the liver between day 7-14 of murine
      GVHD. T cells (CD3+) comprised 65% of hepatic inflammatory cells. alpha-beta and
      gamma-delta cells accounted for 92 and 8%, respectively of hepatic T cells. The
      percentage of CD4+ cells (29%) was 3 times that of CD8+ cells (11%). Lymphocyte
      function-associated antigen-1 (LFA-1) was expressed by the majority of
      inflammatory cells. Thirty per cent of the cells were positive for Mac-1, a
      differentiation marker of macrophages, large granular lymphocytes, and natural
      killer cells. Expression of intercellular adhesion molecule-1 and major
      histocompatibility complex class II (IAd) molecules on bile duct epithelial and
      portal vein endothelial cells was induced during GVHD. These results suggest that
      hepatic GVHD is induced by donor alpha-beta T cells through mechanisms that may
      involve CD4:1Ad and LFA-1:ICAM-1 interactions.

PMID- 7581115
TI  - High-dose cyclosporine and corticosteroids for prophylaxis of acute and chronic
      graft-versus-host disease.
AB  - Twenty-eight consecutive recipients of HLA-identical sibling marrow grafts
      received prophylaxis for GVHD with high-dose cyclosporine (CsA) and
      corticosteroids. CsA 5 mg/kg/day (2.5 mg/kg infused over 4 h twice daily) was
      started on day -1 and continued until patients could take oral CsA (15
      mg/kg/day). CsA doses were adjusted to maintain concentrations between 200-800
      ng/ml (whole-blood HPLC) until the tapering period (days 268-361).
      Methylprednisolone 0.5 mg/kg/day was started on day 7, increased to 1 mg/kg/day
      during days 15-28, and tapered thereafter until discontinuance on day 194. Low
      CsA trough levels occurred in 15 patients (54%) during the i.v. administration
      period. Ten patients (36%) developed grade I and 3 patients (11%) developed grade
      II acute GVHD; there were no cases of grade III or IV disease. The actuarial
      incidence of chronic GVHD was 29% at 1 year but 57% at 2 years due to development
      of chronic GVHD after discontinuation of immunosuppressive agents. High blood CsA
      concentrations in stable outpatients led to dose-limiting nephrotoxicity.
      Infections occurred throughout the period of extended immunosuppression (from 6
      to 12 months) but were not life-threatening. The actuarial incidence of leukemic
      relapse was 18% at 1 year and 25% at 2 years. Actuarial survival at 1 and 2 years
      was 68 and 51%, respectively. Despite the frequent occurrence of low CsA trough
      levels, this regimen appeared to be effective in preventing acute GVHD.
      Immunosuppressive prophylaxis beyond 1 year may be required to reduce late-onset
      chronic GVHD.

PMID- 7581116
TI  - CMV-antigenemia after allogeneic bone marrow transplantation: correlation of CMV
      antigen positive cell numbers with transplant-related mortality.
AB  - One hundred and thirty-four consecutive patients undergoing HLA-identical BMT
      were prospectively followed on a weekly basis for the development of CMV
      antigenemia (CMVAg-emia). End-points of the study were (1) incidence, (2) risk
      factors, and (3) predictive effect on transplant-related mortality (TRM). Fifty
      six patients developed CMVAg-emia between day 8-366 (median 40) with an overall
      actuarial risk of 43%. The median number of positive cells a diagnosis was 4
      (range 1-48) the median maximum number was 6.5 (range 1-435). Positive cells are
      expressed as number/2.5 x 10(5) cells. In multivariate analysis, T cell depletion
      (TCD) (RR 2.9, P = 0.0009) and acute graft-versus-host disease (RR 2.1, P = 0.01)
      were the two risk factors predictive for CMVAg-emia. The risk of developing CMV
      IP was significantly higher in patients with, as compared to patients without,
      CMVAg-emia (P = 0.0005) and occurred mostly in patients who received TCD marrow
      (P = 0.0009) despite treatment with gancyclovir or foscarnet at the time of CMVAg
      emia. TRM was 24% in patients not developing CMVAg-emia; it was 21 and 47% in
      patients with "4" positive cells at diagnosis of CMV (P = 0.008), and 12 vs 54%
      for patients with "6" positive cells during infection (P = 0.0003). Both were
      predictive of TRM in multivariate analysis (P = 0.04 and P = 0.002). In
      conclusion, the risk of developing CMVAg-emia post-allo BMT is influenced by the
      marrow T cell content and by the occurrence of acute GVHD. High numbers of CMV
      antigen positive cells are associated with considerable transplant-related
      mortality, and may therefore identify patients eligible for early aggressive
      therapy.

PMID- 7581117
TI  - Acute myeloid leukemia and myelodysplasia following intensive chemotherapy for
      breast cancer.
AB  - Two major classes of therapy-related acute myeloid leukemias (t-AML) and
      myelodysplastic syndromes (t-MDS) have been described following the use of
      conventional doses of alkylating agents and epipodophyllotoxins. They are
      characterized by distinct clinical presentations and chromosomal abnormalities.
      We report 2 cases of t-AML and 1 case of t-MDS in 3 out of 36 women who underwent
      high-dose chemotherapy and attempted ABMT for breast cancer. Two patients
      developed t-AML 4 and 8 months following the initiation of high-dose chemotherapy
      with or without ABMT. The third patient developed t-MDS 23 months following dose
      intensive chemotherapy and ABMT. Cytogenetic studies of the marrow metaphase
      chromosomes from the two patients who developed t-AML, including FISH analysis in
      1 patient, showed a t(9;11)(p22ng,q23) abnormal chromosome 6 (ring chromosome).
      Neither patient had a preleukemic phase. Cytogenetic studies from the third
      patient who developed t-MDS showed abnormalities of chromosome 5 (-5) and a
      derivative of chromosome 17. The use of multiple chemotherapeutic agents in all 3
      patients makes it difficult to attribute the development of these cases of t
      MDS/t-AML to a single chemotherapeutic agent. The possible role of dose-intensive
      chemotherapy in the development of these secondary malignancies is discussed.

PMID- 7581120
TI  - Allogeneic BMT in a patient with CML and prior disseminated infection by
      mycobacterium avium complex.
AB  - A patient with chronic myeloid leukemia (CML) who developed a disseminated
      infection by mycobacterium avium complex (MAC) was successfully treated with
      rifampin, ethambutol, isoniazid, cycloserin and ciprofloxacin. Diagnosis was
      proven by histologic examination of hepatic biopsy and culture of the liver
      biopsy material. Two years later the patient underwent allogeneic bone marrow
      transplantation (BMT) from an HLA-matched sibling donor. Antimycobacterial
      prophylaxis to MAC with ethambutol, cycloserin and ciprofloxacin was given
      throughout the immediate post-transplant period. On day +25 post-BMT secondary
      prophylaxis was changed to ciprofloxacin and clarithromycin due to hepatic
      toxicity. Treatment was maintained until day 100 without side effects. There was
      no evidence of recurrent mycobacteriosis. Eight months after BMT the patient is
      well, with a good performance status and chronic graft-versus-host disease (GVHD)
      limited to the oral mucosa. Thus, MAC infection prior to transplant need not be a
      contraindication to successful BMT.

PMID- 7581118
TI  - Chronic airflow obstruction in long-term survivors of allogeneic bone marrow
      transplantation.
AB  - Prospective pulmonary function tests (PFTs) of 49 long-term survivors of
      identical sibling bone marrow transplants (BMT) were analysed. Eight (16%)
      developed a persistent pulmonary syndrome characterised by a late onset, cough
      and dyspnoea, hyperinflation or patchy infiltrates on plain radiography and
      episodic bacterial infections. The predominant PFT pattern was obstructive
      (reduced forced expiratory ratio, FER) with a variable restrictive component
      (reduced vital capacity, VC). When compared with the other 41 patients
      (controls), mean FER (53% absolute) and VC (73% predicted) were significantly
      lower at 12 months (P = 0.005). Graft-versus-host disease (GVHD) was the only
      identifiable risk factor (odds ration 7.1). Five of 7 patients compared with 4 of
      31 controls tested at 3 months had an abnormal FER or maximum mid-expiratory flow
      rate (MMFR), but not VC, prior to the onset of symptoms (P = 0.015). Patients
      with mild to moderate disease (FER 50-70%) had stable pulmonary function while
      severe cases progressed despite immunosuppressive agents. Earlier recognition of
      this syndrome by a reduced FER or MMFR may allow the initiation of therapy at a
      potentially reversible stage.

PMID- 7581122
TI  - Comparative survival, quality of life and cost-effectiveness of intensive therapy
      with autologous blood cell transplantation or conventional chemotherapy in
      multiple myeloma.
AB  - We retrospectively compared survival time, quality of life, and the therapy costs
      in 37 patients suffering from newly diagnosed multiple myeloma (MM), divided into
      3 groups. Twelve patients with grade III MM, according to the classification of
      Durie-Salmon, all with widespread lytic lesions (group I), underwent a two-phase
      intensive therapy. They first received high-dose melphalan (HDM), both as tumor
      reducing and blood cell (BC)-mobilizing chemotherapy, subsequently followed by BC
      transplantation. Group II comprising 10 patients, also with grade III MM and with
      characteristics similar to those of group I, were treated with conventional
      polychemotherapy. Finally, group III enrolled 15 patients with lower grade
      disease (grade II) who were also treated with conventional chemotherapy. The
      median overall survival time and the quality of life index were significantly
      lower in group II than in group I (P = 0.0013 and < 0.001 respectively). Although
      the overall survival time of group III (43 months) was similar to that of group
      I, its quality of life index was also significantly lower (P < 0.05). However,
      the total therapy costs of group I were globally higher than those of the 2 other
      groups, but when absolute cost-effectiveness as well as qualitative cost
      effectiveness (corrected for quality of life) were analyzed, the costs per week
      of life gained of group I compared extremely favorably with those of group II
      and, to a lower degree, of group III. Intensive therapy therefore seems capable
      of substantially improving the survival time for high-risk MM patients with
      satisfactory quality of life and at a reasonable cost.

PMID- 7581121
TI  - Allogeneic bone marrow transplantation for postpolycythemic myeloid metaplasia
      with myelofibrosis: a case report.
AB  - Myeloid metaplasia with myelofibrosis develops in about 10% of patients with
      polycythemia vera. We report a case of a 48-year-old female with postpolycythemic
      myelofibrosis successfully treated with allogeneic HLA-matched bone marrow
      transplantation.

PMID- 7581123
TI  - Elevated plasma endothelin concentrations in cyclosporine-treated patients after
      bone marrow transplantation.
AB  - Administration of cyclosporine is often associated with the development of renal
      dysfunction and hypertension. Since recent data from animal experiments provide
      evidence that endothelin, a potent vasoconstrictive peptide, might play a role in
      mediating cyclosporine-related renal and cardiovascular side-effects, the present
      study was designed to investigate whether plasma endothelin concentrations are
      elevated in cyclosporine-treated patients. Plasma endothelin concentrations,
      determined by radioimmunoassay after Sep Pak C18 extraction, were significantly
      elevated in cyclosporine-treated patients after bone marrow transplantation (8.3
      +/- 1.4 ng/l, n = 28) compared to patients not treated with cyclosporine after
      bone marrow transplantation (3.9 +/- 0.2* ng/l, n - 11), patients with
      haematological disorders (3.9 +/- 0.3** ng/l, n = 11) not treated with bone
      marrow transplantation and to normal control subjects (3.1 +/- 0.2*** ng/l, n =
      33) (*P < 0.05, **P < 0.01, ***P < 0.001). Furthermore, plasma endothelin levels
      exhibited a significant correlation with cyclosporine concentrations (r = 0.57, P
      < 0.01). The present data, demonstrating elevated plasma endothelin
      concentrations in cyclosporine-treated patients, suggest that the cyclosporine
      associated renal and cardiovascular side-effects might in part be mediated by
      cyclosporine-induced stimulation of endothelin release.

PMID- 7581119
TI  - Engraftment syndrome in autologous bone marrow and peripheral stem cell
      transplantation.
AB  - Reproducible and characteristic clinical findings of fever, skin rash, capillary
      leak and pulmonary infiltrates have been observed during engraftment in patients
      with autologous bone marrow (BM) and/or peripheral stem cell transplantation
      (PSCT). Two hundred and forty-eight patients were analyzed retrospectively to
      establish the clinical entity, to characterize the clinical course, and to find
      clinical variables affecting the incidence of the syndrome. One hundred and eight
      cases (83.7 +/- 9.4%) of fevers occurring in the periengraftment period (PEN) not
      associated with positive cultures, biopsies, or clinical signs of infection did
      not reveal delayed documentation of concealed infection in 2 weeks after
      engraftment. Capillary leak, pulmonary infiltrates, hypoxia, non-infectious
      neutropenic fever of engraftment and skin rash were found to be interrelated (all
      P < 0.01 except for hypoxia vs rash; P < 0.05). By stepwise discriminant
      analysis, one hundred and thirty-two patients (58.9 +/- 6.4%) were shown to have
      both skin rash and non-infectious neutropenic fever, thereby constituting the
      syndrome. Sepsis in the first week of neutropenia decreased the incidence of the
      syndrome (58.5 +/- 7.7% with sepsis, 89.6 +/- 4.7% without sepsis, P < 0.01).
      Post-transplant granulocyte colony-stimulating factor increased the incidence of
      the syndrome (79 +/- 4.6% with G-CSF vs 48.3 +/- 8.2% without G-CSF, P < 0.01).
      In bone marrow transplantation (BMT), the median time of onset of the syndrome
      was 7 days (range 4-22 days) post-transplant with a median duration of 11 days
      (range 4-28 days) of the initial phase. Thirty-nine patients (17.4 +/- 5.0%)
      revealed a recurrent pattern during the 5th week post-transplant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581124
TI  - Severe hepatotoxicity from granulocyte-macrophage colony-stimulating factor
      administered after autologous bone marrow transplantation.
AB  - We report a case of life-threatening hepatotoxicity following GM-CSF therapy
      after autologous bone marrow transplantation. GM-CSF hepatotoxicity should now be
      considered in the differential diagnosis of post-transplant liver disease.

PMID- 7581125
TI  - Induction of cutaneous 'graft-versus-host like' reaction by recombinant IL-2
      after autologous bone marrow transplantation.

PMID- 7581126
TI  - Erythrocyte polyamine levels: an indication of successful engraftment of bone
      marrow in children.
AB  - We studied the evolution of erythrocyte polyamine levels after 17 autologous bone
      marrow transplants (BMT) in 16 children with malignant diseases. We found that
      the time to the end of aplasia (0.5 x 10(9) granulocytes per liter) could be
      divided into 2 distinct periods. The first is characterized by low erythrocyte
      spermidine (Spd) and spermine (Spm) levels; the second is characterized by normal
      levels of polyamines. Spd and Spm levels were correlated (r = 0.74) during the
      second period, but not during the first period or in the control group.
      Furthermore, the time when Spd concentration was > or = 7 nmol/8 x 10(9)
      erythrocytes (19 +/- 7) was correlated (r = 0.64) with the advent of end of
      aplasia (30 +/- 10). We found no correlation between the numbers of CFU-GM and
      duration of aplasia levels or the duration of period A. The establishment of
      normal erythrocyte spermidine levels is the earliest index of successful marrow
      engraftment.

PMID- 7581127
TI  - Graft-rejection and toxicity following bone marrow transplantation in relation to
      busulfan pharmacokinetics.
AB  - We have determined the relationships between busulfan average concentration at
      steady-state and (1) rejection of graft, and (2) regimen-related toxicity, and
      have evaluated the dependence of busulfan clearance/F on body size and age.
      Patients received 16-30 mg/kg of busulfan followed by cyclophosphamide in doses
      of 120, 150, 174, or 200 mg/kg or 8 g/m2 in preparation for autologous, syngeneic
      or allogeneic grafts varying in compatibility from HLA-matched siblings to HLA
      partially-matched unrelated donors. In a multivariate Cox time-to-rejection
      analysis, only busulfan concentration remained a significant determinant of
      rejection, P = 0.0154. An average concentration of busulfan at steady-state of at
      least 200 ng/ml was needed to avoid rejection of a matched-sibling graft, while
      600 ng/ml was needed to avoid rejection of HLA-partially-matched related or HLA
      matched unrelated donor grafts. The toxicity of the cytoreductive regimen
      correlated with busulfan average concentration at steady-state (rs = 0.717).
      Busulfan clearance/F expressed relative to body weight, ideal body weight or
      surface area declined with age during the first decade of life. Over the entire
      span of age, the coefficient of variation in clearance/F for all ages was similar
      when clearance/F was expressed in absolute terms (ml/min) and when adjusted for
      body surface area; the coefficient of variation was greater for clearance/F when
      expressed relative to total or ideal body weight. We conclude that busulfan
      concentration in plasma is an important determinant of graft survival and regimen
      related toxicity, and that the variability of busulfan pharmacokinetics with age
      precludes the use of a fixed dose for all ages and indications.

PMID- 7581128
TI  - DNA typing for bone marrow engraftment follow-up after allogeneic transplant: a
      comparative study of current technologies.
AB  - DNA typing is widely used to document engraftment after allogeneic bone marrow
      transplantation (BMT). Most DNA typing procedures discriminate allogeneic
      engraftment on the basis of DNA length polymorphisms or sequence variations found
      in variable number of tandem repeat (VNTR) loci, or the presence of Y chromosome
      specific DNA We have compared 3 types of VNTR analysis, their respective mode of
      allele detection and Y chromosome DNA detection in order to assess the strengths
      and limitations of each approach. Chimerism was assessed in 8 recipients after
      allogeneic BMT. Samples were subjected to 6 restriction fragment length
      polymorphism (RFLP) loci-analysis using radioactivity, 2 amplified fragment
      length polymorphism (AmpFLP) loci-analysis using a silver-stain mode of
      detection, 12 short tandem repeat (STR) loci-analysis using fluorescence
      detection and Y chromosome analysis. We evaluated each procedure for its ability
      to (1) discriminate sibling donor-recipient pairs in our samples; (2) generate a
      concordant chimerism diagnosis; and (3) detect and assess the contribution of
      minority components in mixed-chimera situations. In sex-mismatched BMTs with a
      female graft donor, Y chromosome probing has proven most efficient. In all other
      cases, AmpFLPs proved to be a rapid and efficient procedure with sufficient
      discriminating capability and sensitivity to warrant their use in clinical
      settings. STRs are rapid as well but require a larger loci complement to
      discriminate efficiently and they do not currently detect, under our conditions,
      all mixed chimeras. RFLPs are clearly superior at discriminating siblings but are
      time-consuming and serve best in cases where AmpFLP and STR analyses fail.

PMID- 7581129
TI  - Granulocyte colony-stimulating factor mobilizes primitive hematopoietic stem
      cells in normal individuals.
AB  - We studied the hematopoietic activity of peripheral blood stem cells (PBSC)
      mobilized by recombinant human granulocyte colony-stimulating factor (G-CSF)
      using semisolid and long-term culture systems (LTC) in 5 normal individuals.
      Following 2 or 3 daily subcutaneous injections of G-CSF (filgrastim; 1.5
      micrograms/kg), not only committed progenitors including CFU-GM, BFU-E, and CFU
      Mix, but also long-term culture initiating cells (LTC-IC) were increased in the
      peripheral blood. When the cells derived from CFU-GM, BFU-E and CFU-Mix colonies
      were replated for secondary colony formation, a minor fraction of CFU-GM and CFU
      Mix colonies formed after 3 days of G-CSF stimulation in vivo could produce
      secondary colonies. Moreover, the replating capacity of primary colonies from 5
      week-old LTC initiated after 3 days of G-CSF stimulation was increased compared
      to that from 5-week-old LTC initiated in a 'steady-state'. These observations
      indicate that G-CSF can mobilize very primitive progenitors (LTC-IC) along with
      committed progenitors into the circulation and suggest that some of these G-CSF
      mobilized progenitors may retain self-renewal capacity.

PMID- 7581130
TI  - Transplantation of G-CSF mobilized allogeneic peripheral blood stem cells in
      rabbits.
AB  - Mobilized peripheral blood precursor cells (PBPC) are used with increasing
      frequency to restore autologous hematopoiesis following high-dose radio
      chemotherapy. The success of this method has aroused interest in the use of
      mobilized PBPC for allogeneic transplants. This approach would eliminate the need
      for marrow aspiration and general anesthesia. In this project we tested the
      feasibility of allogeneic histoincompatible PBPC transplants in rabbits. Adult
      outbred Red Burgundy rabbits were used as donors, histoincompatible New Zealand
      White rabbits of the opposite sex as recipients. One individual donor was used
      for one individual recipient. Conditioning consisted of 10 Gy total body
      irradiation (TBI). Donor animals were pre-treated with recombinant human
      granulocyte colony-stimulating factor (rh G-CSF) given s.c. at 10 micrograms/kg
      daily. Three schedules of PBPC collection and reinfusion were tested in 3 groups
      of animals, each consisting of 5 donor recipient pairs: (A) PBPC were collected
      either on days -2, -1 and 0, and infused at once after TBI on day 0; (B)
      collected and infused on days 0, +2, +4, +7, +9, and +11; (C) collected on 3
      consecutive days, cryopreserved for 1 month and infused on day 0 followed by 3
      fresh donations on days +4, +8 and +11. The median amount of blood processed from
      donor animals was 470 ml (312-602) containing about 10 x 10(8) (5-71 x 10(8))
      nucleated cells. Recipient animals received a median of 2.7 x 10(8) cells/kg
      equivalent to 9.6 x 10(4) colony-forming units granulocyte-macrophages (CFU
      GM)/kg (data derived from Group C of the animals).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7581132
TI  - Relapse of multiple myeloma after autologous transplantation: survival after
      salvage therapy.
AB  - Owing to lack of progress with standard chemotherapy and the presence of a dose
      response effect for alkylating agents, autotransplantation is performed with
      increasing frequency for multiple myeloma (MM). However, sustained relapse-free
      survival is still infrequent. We studied 94 patients who had relapsed following
      autotransplantation, in order to evaluate the efficacy of further therapy. Post
      transplant salvage treatment consisted of either standard dose therapy (53) or
      transplantation with an intensive preparative regimen (with autograft support in
      31 and allogeneic transplantation in 10). Complete remission (CR) rate, event
      free and overall survival were assessed and prognostic variables identified in a
      multivariate regression analysis. With a median follow-up of 11 months, the
      projected overall survival at 18 months for all patients is 59%. A multivariate
      analysis identified pre-salvage beta-2-microglobulin (B2M) < or = 2.5 mg/l (P =
      0.0002) and late relapse after the preceding transplant ( > 12 months; (P = 0.02)
      as independent significant favorable variables for overall survival. By combining
      pre-salvage B2M and the time to relapse, 2 risk groups of patients could be
      identified with significantly different overall survival: those with at least one
      favorable variable had a projected survival at 18 months of 79%, compared to 38%
      for patients with no favorable variable. Transplantation performed as primary
      salvage therapy was associated with a significantly prolonged survival (P =
      0.009), although this may be more a reflection of the way salvage therapy was
      selected.

PMID- 7581133
TI  - Single-centre experience of peripheral blood stem cell transplantation using
      cryopreservation by immersion in a methanol bath.
AB  - A simplified method to remove and cryopreserve peripheral blood stem cells (PBSC)
      was utilised to restore the bone marrow in 31 patients with haematological or
      solid neoplasms after ablative chemotherapy. Mobilization was performed with
      subcutaneous G-CSF, starting 4 days before the first PBSC harvest and continuing
      to the last day of harvest. Cryopreservation was carried out by freezing cells to
      -80 degrees C after addition of autologous fresh plasma with DMSO, in a methanol
      bath and non-programmed freezer. The PBSC were reinfused in all cases. The mean
      quantity of CD34 cell (x 10(6)/kg) infused was 6.5 +/- 6.7. The mean number of
      procedures needed to harvest an appropriate number of PBSC was 3.6 +/- 1.3. The
      mean times necessary to recover more than 0.5 x 10(9)/l granulocytes were 11 +/-
      4 (8-30) days and 23 +/- 13 (8-55) days to obtain more than 20 x 10(9)/l
      platelets. These results confirm our method as very effective in achieving a high
      quality harvest, and it was used in paediatric and adult patients without
      problems. This procedure, using a non-programmed freezer, simplifies and reduces
      enormously the cost of the technical measures currently used, enabling their
      adoption in almost any clinical oncological institution.

PMID- 7581131
TI  - Busulphan and melphalan prior to autologous transplantation for myeloid
      malignancies.
AB  - We report our experience with 67 patients with myeloid malignancies (acute
      myeloid leukaemia (AML) or chronic myelogenous leukaemia (CML) conditioned with
      busulphan and melphalan as preparation for autologous haemopoietic cell
      transplantation. The major non-haematological toxicities were severe mucositis,
      nausea and vomiting, but the marrow aplasia was delayed and of short duration.
      The anti-tumor effect was appreciable with subsequent chronic phase (CP) obtained
      in 30/31 CML in transformation and complete remission (CR) obtained in 2/3
      refractory AML. Among 32 patients treated while they had no evidence of active
      disease, 12 remained in CR or CP with a median follow-up of 54.7 months.

PMID- 7581134
TI  - Peripheral blood stem cell transplantation after high-dose therapy in patients
      with malignant lymphoma: a retrospective comparison with autologous bone marrow
      transplantation.
AB  - We report the results of peripheral blood progenitor cell (PBPC) harvesting in 22
      patients with lymphoma who underwent leucapheresis after cells were mobilised
      using 3 g/m2 cyclophosphamide and G-CSF. In 19 patients, the total CFU-GM
      collected was greater than 7.5 x 10(4)/kg. These patients underwent successful
      autologous PBPC transplantation. This group of patients was compared to a
      historical group of 24 patients with lymphoma who underwent ABMT with the same
      conditioning chemotherapy. The time to engraftment of neutrophils to 0.5 x
      10(9)/l was significantly reduced (median 11 days vs 19 days, P < 0.0001) and
      consequently in-patient stay was reduced (median 21 days vs 28 days, P < 0.001).
      Blood product support (median 3 vs 4 units blood, P = 0.02; median 15 vs 40 units
      platelets, P = 0.005) and use of TPN (median 0 days vs 8 days, P < 0.001) were
      reduced. We estimate a saving of approximately pounds 2370 per patient using PBPC
      for autologous transplantation compared to bone marrow progenitor cells. This
      saving is significant (P < 0.001).

PMID- 7581136
TI  - Natural killer cell regeneration after transplantation with mafosfamide purged
      autologous bone marrow.
AB  - Autologous bone marrow transplantation (ABMT) is used increasingly for the
      treatment of acute leukemias, lymphomas and solid tumors. Since ABMT is burdened
      by high risk of relapse, mafosfamide or 4-hydroperoxycyclophosphamide chemical
      marrow purging is employed. Mafosfamide acts by exerting a potent cytotoxic
      effect and by promoting apoptosis of leukemic cells. A third proposed mechanism
      of action involves an effect on immune regeneration in vivo. It was the aim of
      this study to investigate natural killer (NK) cell regeneration in a group of
      patients undergoing mafosfamide-purged ABMT. Fifteen patients (8 acute
      myelogenous leukemia, AML; 4 acute lymphoblastic leukemia, ALL; 3 non-Hodgkin's
      lymphoma, NHL) were treated with high-dose chemotherapy followed by
      transplantation with marrow purged with mafosfamide. Prior to ABMT and at
      different intervals thereafter, NK cell number and function were studied by
      evaluating the percentage of circulating CD16 positive cells and cytotoxic
      activity against the leukemic cell line, K562. In comparison to pre-ABMT values,
      AML patients showed a significant increase in cytotoxic activity, expressed as
      percentage of chromium release (42.5 +/- 3 vs 32.5 +/- 6, P < or = 0.025 at 4
      months) which still persisted at 12 months post-ABMT (54 +/- 6, P < or = 0.05).
      The behavior of NK functional activity was paralleled by an increase of the
      percentage of CD16-positive cells (8.4 +/- 2.2 vs 5 +/- 1.3, P < or = 0.05 at 4
      months; 12.8 +/- 2.4, P < or = 0.005 at 12 months post-ABMT). Similar significant
      and long-lasting increments in NK cells were also found in NHL patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581135
TI  - DHAP regimen plus G-CSF as salvage therapy and priming for blood progenitor cell
      collection in patients with poor prognosis lymphoma.
AB  - We studied 14 patients affected by lymphoma to assess the toxicity, efficacy and
      mobilization capability of salvage DHAP regimen followed by G-CSF 5
      micrograms/kg/day. Ten patients were affected by intermediate-grade NHL and 4 by
      HD; all of them were in relapse or in PR. We administered a total of 34 courses
      of DHAP plus G-CSF (median 2 per patient; range 1-5) and did not observe either
      life-threatening extrahematologic toxicity or severe infections during the short
      neutropenic period. A significant tumor burden reduction was observed in 86% of
      patients (50% CR, 36% PR). A total of 35 aphereses were performed (median 3 per
      patient; range 1-5). The hemopoietic progenitors showed a very rapid increase
      from day +11 with a synchronous and impressive peak on day +13. We collected a
      median of 2.6 x 10(6)/kg CD34+ cells, 10 x 10(4)/kg CFU-GM, 5 x 10(4)/kg BFU-E
      and 0.5 x 10(4)/kg CFU-GEMM per apheresis. All patients transplanted with PBPC
      had a rapid and sustained hematological recovery. The DHAP regimen followed by G
      CSF proved to be a very effective and well-tolerated schedule for debulking
      disease before transplantation and for enhancing progenitor cell mobilization.

PMID- 7581137
TI  - Impact of cytogenetic abnormalities on outcome of bone marrow transplants in
      acute myelogenous leukemia in first remission.
AB  - This study analyzed the impact of cytogenetic abnormalities on outcome of 1516
      HLA-identical sibling bone marrow transplants for acute myelogenous leukemia
      (AML) in first remission reported to the International Bone Marrow Transplant
      Registry by 188 centers. 708 patients (47%) had cytogenetic studies performed.
      Transplant outcome in these subjects was similar to the 808 in whom cytogenetic
      studies were not performed. One or more cytogenetic abnormalities were detected
      in 284 (40%) of subjects studied. Relapse rates were higher and leukemia-free
      survival lower in patients with poor prognosis abnormalities vs those with no
      abnormality or with good or intermediate prognosis abnormalities (relative risk
      of relapse 2.40, P < 0.01; relative risk of treatment failure 1.68, P < 0.03). We
      conclude that cytogenetic abnormalities correlated with increased relapse in
      patients treated with chemotherapy. HLA-identical sibling transplants are
      similar.

PMID- 7581138
TI  - High-dose busulfan and melphalan before bone marrow transplantation for acute
      nonlymphoblastic leukemia.
AB  - Fourteen patients with acute nonlymphoblastic leukemia (ANLL) (n = 13) or
      juvenile chronic myelomonocytic leukemia (n = 1) were transplanted after
      conditioning with high-dose busulfan (4 mg/kg daily on days -7 to -4) and
      melphalan (180 mg/m2 on day -2). This protocol was designed for patients
      considered unable to receive standard conditioning regimens with cyclophosphamide
      and/or TBI. Five patients (4 children and 1 adult) received a second allogeneic
      BMT in untreated early marrow relapse after a first BMT. There were 3 procedure
      related deaths (PRD), 2 during aplasia and 1 from acute GVHD. Two patients
      survived the procedure; 1 relapsed at 6 months and 1 is alive at 43+ months. Nine
      subjects (8 children and 1 adult) received an autologous BMT, 7 in first and 2 in
      second complete remission (CR). Of the 7 patients grafted in first CR, there was
      1 PRD, 2 relapses at 3 and 15 months, and four are alive at 38 to 82+ months. One
      patient grafted in second CR relapsed at 7 months and 1 is alive at 67+ months.
      Toxicities were mild or moderate in autologous BMT recipients, mainly affecting
      the gastrointestinal tract. In the allogeneic BMT group, there were more moderate
      to severe toxicities, including 3 cases of moderate-severe renal toxicity; no
      cases of such toxicity were seen in ABMT recipients. Two cases of HVOD occurred,
      1 in each group. These results are encouraging, although the small patient group
      does not allow any firm conclusions.

PMID- 7581141
TI  - HLA-haploidentical umbilical cord blood stem cell transplantation in a child with
      advanced leukemia: clinical outcome and analysis of hematopoietic recovery.
AB  - Growing attention has been focused on cord blood as a source of transplantable
      hematopoietic stem cells. However, clinical experience is rather limited. In this
      study we describe a child with advanced acute lymphoblastic leukemia who received
      an HLA-haploidentical cord blood transplant. The patient was transplanted in
      third complete remission after conditioning with fractionated total body
      irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of
      cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg
      and 0.25 x 10(4) CFU-GM/kg, were infused. Cyclosporine and prednisone were
      administered for graft-versus-host disease (GVHD) prophylaxis. The patient
      received G-CSF from day +1 to day +35, but no improvement in granulocyte counts
      was observed. Therefore, administration of GM-CSF was started on day +36 to day
      +59, which resulted in a significant increase in white blood cells and
      granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte
      count > 0.5 x 10(9)/l by day +41. The presence of donor-derived cells could be
      documented in the peripheral blood and bone marrow of the patient by cytogenetic
      analysis, HLA phenotyping and DNA studies. Forty-one days after transplant,
      clonogenic bone marrow assays showed the presence of low frequencies of primitive
      hematopoietic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The
      chimerism was complete and no host-derived cells could be detected. However, the
      engraftment was restricted to the myeloid lineage whereas lymphoid and
      megakaryocytic engraftments were inadequate. The immunophenotype of the patient's
      peripheral blood showed the presence of T lymphocytes expressing an immature
      phenotype (CD2+ CD3-) at day +21.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581142
TI  - Autologous bone marrow or peripheral blood stem cell transplantation followed by
      maintenance chemotherapy for adult acute lymphoblastic leukemia in first
      remission: 50 cases from a single center.
AB  - The aim of this study was to evaluate the use of maintenance chemotherapy after
      autotransplantation in adult acute lymphoblastic leukemia (ALL), and to compare
      the relative durability of marrow and peripheral blood stem cell grafts to
      chemotherapy. Fifty consecutive ALL patients received 200 mg/m2 melphalan alone
      or 110 mg/m2 melphalan with total-body irradiation in first remission, followed
      by autologous marrow (ABMT, n = 38) or peripheral blood stem cells (PBSCT, n =
      12). After hematologic recovery, 6-mercaptopurine and methotrexate were
      administered for 2 years. 6-mercaptopurine could be given to 78.9% of ABMT
      recipients at a median daily dose of 33.5 mg/m2, and to 91.7% of PBSCT recipients
      at a median daily dose of 44.1 mg/m2. ABMT recipients started 6-mercaptopurine at
      a median of 58.5 days post-transplant, and PBSCT recipients at 32 days (P =
      0.002). 52.6% of ABMT recipients and 75% of PBSCT recipients received weekly
      methotrexate. No graft failure was seen as a result of chemotherapy. The
      actuarial 5-year probabilities of overall survival, survival in first remission
      and relapse were 56.2, 53.2, and 30.6%, respectively. We conclude that
      administration of maintenance chemotherapy after autografting in adult ALL may
      reduce relapse. A randomized study is required to evaluate the relative efficacy
      of PBSCT vs ABMT, and the role of post-transplant maintenance chemotherapy.

PMID- 7581143
TI  - Association of increased bronchoalveolar lavage fluid albumin and serum beta 2
      microglobulin with pulmonary complications after allogeneic bone marrow
      transplantation.
AB  - The aim of this prospective study was to identify markers in bronchoalveolar
      lavage fluid (BAL fluid) and serum predictive for the development of pulmonary
      complications in the early phase (< 50 days) post-BMT. Concentrations of BAL
      fluid albumin (alb) and serum beta 2-microglobulin (S-beta 2m,) were determined
      10 days before BMT (BAL-B, baseline) and on day 1 post-BMT (BAL-1) in 20 patients
      who subsequently developed pulmonary complications (group 1) and in 66 patients
      who remained free of complications for a minimum of 12 months (group 2). Median
      BAL fluid alb concentrations were significantly (P < 0.05) higher in group 1
      patients as compared to group 2 patients at BAL-B (40 vs 28 mg/l) and at BAL-1
      (30 vs 15 mg/l). S-beta 2m at BAL-1 was also significantly elevated in group 1
      patients (median 1.3 mg/l) compared to group 2 patients (median 1.15 mg/l). Using
      cut-off values for BAL fluid alb (> 23 mg/l) and S-beta 2m (> 0.8 mg/l) we
      identified 12 patients out of 19 who developed subsequent pulmonary complications
      from 12 out of 62 patients without such complications, 1 day post-BMT.

PMID- 7581140
TI  - Circulating progenitors following high-dose sequential (HDS) chemotherapy with G
      CSF: short intervals between drug courses severely impair progenitor
      mobilization.
AB  - Sequential administration of high-dose chemotherapy courses possibly allows
      extensive in vivo purging before circulating progenitor collection for autograft.
      To evaluate whether progenitor cell mobilization was negatively affected by
      repeated high-dose chemotherapy courses, we studied 23 lymphoma patients
      undergoing the HDS regimen. The scheme includes the sequential administration of
      cyclophosphamide (CY) given at 7 g/m2 and etoposide (VP16) given at 2 g/m2, each
      followed by G-CSF (filgrastim) at 5 micrograms/kg/day. Eleven patients received
      the standard HDS sequence, with a short interval between first and second
      myelotoxic courses of less than 45 days (median: 30 days); the remaining 12
      patients received a modified HDS where the interval between first and second high
      dose course was protracted over 2 months (median: 70 days); in this latter group,
      2 to 4 conventional debulking courses were delivered prior to HDS. In patients
      receiving the standard HDS, progenitor mobilization following the first course
      was consistently high (median circulating CFU-GM/ml peak value: 29,022); however,
      significantly lower values were observed at the second course (median CFU-GM/ml
      peak value 3757, P = 0.002). Circulating BFU-E and CD34+ cell values paralleled
      those of CFU-GM. No significant difference was observed in progenitor
      mobilization following either course in patients receiving HDS with extended
      interval (median circulating CFU-GM/ml peak value: 14,363 vs 9208, at first and
      second course respectively, P = 0.27). Eleven patients had their progenitor cells
      harvested following the second delayed course and 2-4 leucaphereses allowed very
      satisfactory harvests in all of them (CFU-GM/kg ranging from 39-340 x
      10(4)).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581139
TI  - Antiemetic efficacy and pharmacokinetics of intravenous ondansetron infusion
      during chemotherapy conditioning for bone marrow transplant.
AB  - We investigated the antiemetic efficacy and safety of intravenous ondansetron
      infusion in the BMT setting. We conducted prospective randomized comparison
      trials between ondansetron at 2 dose levels and metoclopramide (MCP) plus
      droperidol for the prevention of chemotherapy-induced nausea and vomiting in 2
      patient populations scheduled to undergo BMT. One patient population (n = 30)
      received CY alone, the other population (n = 30) received combination
      chemotherapy of Bu and CY. The CY alone group received ondansetron for 3 days,
      and the Bu/CY group received ondansetron for 7 days. The primary endpoints were
      emesis control and nausea. Secondary endpoints included acute (headache, diarrhea
      and sedation) and delayed (engraftment and regimen-related) side-effects. In both
      trials, ondansetron provided better emesis control than did MCP plus droperidol
      during CY administration (P = 0.009, 3-day trial; P = 0.0022, 7-day trial). There
      was a wide interpatient variation in serum ondansetron levels, although group
      averages were proportional to the dose administered. Intrapatient day-to-day
      variation was 10-30% and did not change significantly with concurrent CY
      administration. Antiemetic efficacy did not correlate with ondansetron serum
      levels at the doses tested. Headache incidence was similar in all groups.
      Sedation was highest in the MCP plus droperidol group (P = 0.048, 3-day trial; P
      = 0.016, 7-day trial). No statistically significant differences in engraftment or
      regimen-related toxicities were observed between groups in either trial.
      Ondansetron appears to be a safe and efficacious antiemetic during conditioning
      for BMT.

PMID- 7581145
TI  - Chronic cholestasis in patients after allogeneic bone marrow transplantation:
      several diseases are often associated.
AB  - From 1984 to 1991, 514 patients were treated by BMT in 1 center. 254 patients
      survived more than 3 months and, in 38 patients, 47 liver biopsies were performed
      for chronic liver dysfunction characterized by cholestasis. The aim of the
      present study was to evaluate the possible causes of liver disease at the time of
      biopsy. One clinician analyzed clinical data and was able to propose up to 3
      diagnoses including GVHD, viral hepatitis, drug-related hepatitis, chronic veno
      occlusive disease (VOD) or other. Two pathologists reviewed histologic sections
      and were also able to propose up to 3 diagnoses. Clinically, 1, 2 or 3 diagnoses
      were proposed in 30, 60 and 10% of cases, respectively. Pathologically, 1, 2 or 3
      diagnoses were proposed in 13, 62 and 25%, respectively. Histologic changes of
      GVHD were present in 40 of 47 biopsies and concordance between the clinician and
      the pathologists on the presence of GVHD lesions was found in 77% of biopsies.
      Viral hepatitis was proposed 22 times by the clinician and 19 times by
      pathologists. Viral hepatitis, usually hepatitis C, was associated with GVHD in
      16 cases. Diagnoses of chronic VOD and drug-related hepatitis were proposed less
      often. In summary, more than 1 diagnosis was suggested for many of the patients
      studied, GVHD being the most frequent. The simultaneous presence of GVHD, viral
      diseases, chronic VOD and drug-induced diseases could explain the high incidence
      of cholestasis in the long-term post-BMT.

PMID- 7581146
TI  - Suprapubic cystotomy as treatment for severe hemorrhagic cystitis after bone
      marrow transplantation.
AB  - We analyzed the success of suprapubic cystotomy in patients with severe
      hemorrhagic cystitis after bone marrow transplantation. Seventy-three out of 963
      patients developed severe hemorrhagic cystitis which resulted in urinary tract
      obstruction after high-dose cytoreductive therapy. Eleven patients (15%) failed
      medical treatment and required emergency suprapubic cystotomy. Three of these
      patients died of other complications prior to resolution of HC. Of the remaining
      8 patients who underwent surgery, 4 are alive. The mortality rate was
      significantly higher in patients who required surgery than in those who responded
      to medical therapy. Patients whose HC required surgery also had a greater
      transfusion requirement than those who responded to medical therapy. We conclude
      that surgical treatment of severe HC should be undertaken only after failure of
      medical therapy.

PMID- 7581144
TI  - Gonadal function and psychosexual adjustment in male long-term survivors of bone
      marrow transplantation.
AB  - Gonadal function and psychosexual adjustment were evaluated in 29 male patients
      after autologous and allogeneic BMT (mean post-BMT time 35.6 months). Patients
      were divided into groups according to their interval from transplant in order to
      evaluate gonadal function throughout the post-BMT years. Thyroid-stimulating
      hormone (TSH) and free thyroxine (FT4) were normal throughout the post-BMT years.
      Follicle-stimulating hormone (FSH) and luteinising hormone (LH) were increased
      throughout the years after BMT, suggesting moderate compensated hypogonadism.
      Hyperprolactinaemia was observed only in the 2nd year post-BMT and testosterone
      levels were normal, suggesting that Leydig cells can withstand alkylating agents
      or TBI. Psychosexual functioning in BMT survivors was compared with that of a
      group of mixed-diagnosis cancer patients (n = 30) and a group of healthy young
      subjects (n = 119). Long-term BMT survivors had similar psychosexual adjustment
      to that of other cancer patients who had received less intensive chemotherapy.
      Half the patients were dissatisfied with their current sex life. Major problems
      included impotence/erectile difficulties (37.9%), low sexual desire (37.9%) and
      altered body image (20.7%). However, both BMT survivors and cancer patients had
      significantly higher psychosexual dysfunction compared with healthy subjects. The
      type of chemotherapy, TBI (either single-dose or fractionated), type of
      transplant and post-BMT time did not correlate with either gonadal or
      psychosexual functioning.

PMID- 7581147
TI  - Therapeutic plasma exchange does not appear to be effective in the management of
      thrombotic thrombocytopenic purpura/hemolytic uremic syndrome following bone
      marrow transplantation.
AB  - Recognition of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic
      syndrome (HUS) following BMT has increased in recent years. The pathogenesis and
      etiology may be related to endothelial cell damage secondary to irradiation
      and/or CsA. Optimal management of this condition remains unclear. Due to
      similarity between this syndrome and classical TTP, patients with TTP/HUS
      following BMT are commonly treated with therapeutic plasma exchange (TPE). We
      describe our experience with 9 such patients who were treated with TPE (8 cases)
      and immunoadsorption with a Staphylococcal Protein A column (1 case). The
      exchanges were done with fresh frozen plasma and/or cryoprecipitate-depleted
      frozen plasma. Out of 8 patients treated with TPE, 6 died within 2 months of TPE
      due to secondary infections, metabolic disturbances and progression of TTP/HUS.
      Of these 6 patients, 5 had no hematological response, while 1 had hematological
      improvement. Two patients are alive 4 and 3 years later, however, they had shown
      only minimal hematological response at the end of 28 and 20 TPE, respectively.
      Their renal function remains stable but severely reduced. The ninth patient who
      received Staphylococcal Protein A column treatment died within 5 days of
      treatment without hematological improvement. Thus, in contrast to its
      effectiveness in classical TTP, TPE does not appear to be as effective in the
      management of well established TTP/HUS following BMT.

PMID- 7581148
TI  - In vitro LAK (lymphokine activated killer) activity following autologous
      peripheral blood stem cell is significantly greater than that following
      autologous bone marrow and allogeneic bone marrow transplantation.
AB  - LAK activity is known to increase following autologous and allogeneic bone marrow
      transplant and peripheral blood stem cell transplant (PBSCT). The aim of this
      study was to directly compare the 3 types of transplant and the LAK activity
      generated. LAK activity following PBSCT is significantly greater than that
      following autologous bone marrow transplantation and even allogeneic
      transplantation up to 8 weeks. The type of killer cells generated is similar for
      the different types of transplants, with most killing activity following PBSCT
      due to CD56+ cells, though CD3+ cells also contribute. This study would suggest
      that attempts to augment the graft-versus-leukaemia effect is more likely to be
      successful following PBSCT than autologous bone marrow transplantation.

PMID- 7581149
TI  - Immunotherapy with interleukin 2 with or without lymphokine-activated killer
      cells after autologous bone marrow transplantation for malignant lymphoma: a
      feasibility trial.
AB  - Early relapse remains a major challenge after autologous bone marrow transplant
      for malignant lymphoma (ML). It is postulated that consolidative immunotherapy
      with interleukin 2 (IL-2) with or without lymphokine-activated killer (LAK) cells
      administered after autologous bone marrow (ABMT) or peripheral blood stem cell
      transplantation (PBSCT) for ML might eradicate residual disease and reduce
      relapse rates. A previous trial identified an IL-2 regimen that could be
      administered early after ABMT. This paper presents the clinical results of 16
      patients with ML, who participated in a study to determine whether LAK cells
      could be administered after ABMT with this IL-2 regimen, as well as 6 patients
      who received IL-2 alone after ABMT or PBSCT. Seventeen patients with non
      Hodgkin's lymphoma (NHL), and 5 with Hodgkin's disease (HD), underwent ABMT (20
      patients) or PBSCT (2 patients). At the time of transplantation, 7 patients were
      in untreated or chemotherapy-sensitive first relapse, 3 were in CR2, and 12 were
      beyond CR2. Beginning 22-85 days (median 43) after ABMT/PBSCT, patients received
      IL-2 at 3.0 x 10(6) U/m2/day by continuous infusion days 1-5 of the IL-2
      protocol. On protocol days 7-9 the first 16 patients underwent apheresis for LAK
      cell generation. The cells were cultured in IL-2 for 5 days and were infused on
      days 12-14. Low-dose IL-2 (0.9 x 10(6) IU/m2/day) was administered on days 12-21
      in the outpatient department. Patients received a median of 148 (62-279) x 10(9)
      LAK cells. LAK cell infusions were associated with transient fevers, chills and
      dyspnea in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581150
TI  - Requirement for B cells in T cell priming to minor histocompatibility antigens
      and development of graft-versus-host disease.
AB  - Increased understanding of minor histocompatibility complex (MiHC) antigen
      presentation to donor T cells may permit methods to modulate graft-versus-host
      disease (GVHD), a major complication of allogeneic bone marrow transplantation
      (BMT). Previously, we described the importance of B cells as antigen presenting
      cells in T cell responses to a virally induced murine leukemia. Using a B cell
      deficient mouse model in which mice receive either control rabbit immunoglobulin
      (RIgG) or rabbit anti-IgM mu chain from birth (B cell deficient), we evaluated
      whether B cells were necessary for T cell responses to MiHC and the induction of
      GHVD. Normal and B cell deficient C57BL/6 (H-2b) mice were primed with BALB.B (H
      2b; MiHC incompatible) spleen cells and evaluated > 4 weeks later in vitro. While
      splenic or lymph node T cells obtained from BALB.B primed control C57BL/6 mice
      demonstrated strong in vitro proliferative responses to MiHC mismatched targets,
      B cell deficient hosts were markedly reduced to 14-42% of controls. Similarly, a
      strong MiHC specific cytolytic T cell response was observed in control C57BL/6
      mice (53-100% specific cytotoxicity) whereas B cell depleted recipients had no
      activity (< or = 5% specific lysis). The role of B cells in GVHD was evaluated
      using a MiHC disparate mouse model (LP/J donor into C57BL/6 recipient). We found
      that 12% of B cell depleted recipient mice receiving B cell depleted donor cells
      developed GVHD compared to 50% of RIgG control mice. B cell depletion of donor
      cells only, resulted in a similar result with 0% of mice receiving B cell
      depleted donor cells developing GVHD compared to 38% of controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581151
TI  - Long-term storage of human fetal haematopoietic progenitor cells and their
      subsequent reconstitution. Implications for in utero transplantation.
AB  - Haematopoietic progenitor cells were isolated from human fetal liver, obtained
      between 6 and 15 weeks gestation. After preparation of a single cell suspension,
      the cells were stored using a stepwise freezing protocol; taking the cells from
      room temperature through -70 degrees C to liquid nitrogen. Viability (trypan blue
      exclusion), morphology (Leishman stain), identification of cell type (flow
      cytometry) and growth characteristics in semi-solid culture medium were assessed
      using the fresh cell suspension. We were able to confirm that the predominant
      cells in human fetal liver up to about 15 weeks gestation are those of the
      erythroid lineage. It was established that viability in excess of 75% was
      required to ensure adequate growth in culture after frozen storage and it was
      deemed important to ensure morphological integrity of the cell preparations. The
      colonies formed in culture were observed to be producing haemoglobin between 7
      and 9 days after initial seeding. We have determined that cells can be stored in
      liquid nitrogen for up to 2 years without loss of (1) viability, (2)
      morphological features and (3) ability to form colonies and produce haemoglobin
      in culture. These findings offer encouragement for the implementation of a cell
      bank to support an in utero transplantation programme.

PMID- 7581152
TI  - Nephrotic syndrome in a bone marrow transplant recipient with chronic graft
      versus-host disease.
AB  - A 21-year-old male developed massive proteinuria and microscopic hematuria, 1
      year after allogeneic BMT for acute lymphoblastic leukemia. These symptoms
      occurred during an exacerbation of chronic cutaneous graft-versus-host disease
      (GVHD). Renal biopsy revealed granular deposits of IgG and IgM along the
      glomerular basement membrane, and subepithelial electron dense deposits. A
      diagnosis of membranous nephropathy was made. With prednisolone therapy
      proteinuria decreased gradually, and amelioration of cutaneous lesions was also
      noted. It was speculated that the disordered immune regulation of chronic GVHD
      resulted in the development of immune complex nephritis.

PMID- 7581153
TI  - Treatment of acute renal failure with urodilatin after unrelated bone marrow
      transplantation in an 18-month-old boy.
AB  - Acute renal failure was imminent in an 18-month-old male infant 20 days after
      unrelated BMT. The infant was treated with urodilatin (URO), a natriuretic
      vasorelaxant peptide. Diuresis increased 2 h after the commencement of URO
      infusion and the furosemide infusion was reduced from 5 mg/h to 2.5 mg/h. After
      seven days of URO treatment diuresis was normal, the serum creatinine level had
      decreased, and furosemide was reduced from 12 mg/kg bw/d to 1.8 mg/kg bw/d. No
      side effects were observed either during or following URO therapy. We consider
      URO to be a promising drug for the treatment, without any apparent side effects,
      of imminent or manifest acute renal failure in infants following BMT.

PMID- 7581154
TI  - Successful treatment with ganciclovir of presumed Epstein-Barr meningo
      encephalitis following bone marrow transplant.
AB  - Epstein-Barr virus-specific polymerase chain reaction was used to diagnose EBV
      meningo-encephalitis in a bone marrow transplant recipient. The patient made
      complete recovery with ganciclovir treatment. Pitfalls in diagnosis with EBV-PCR
      and the potential therapeutic efficacy of ganciclovir in EBV infections are
      discussed.

PMID- 7581156
TI  - Oncocytic metaplasia of bile duct epithelium in hepatic GVHD.
AB  - A 15-year-old female underwent matched unrelated BMT for chemotherapy resistant
      ALL. She died 3 months later from septicaemia complicating grade IV GVHD. Light
      and electron microscopic examination of the post-mortem liver confirmed GVHD and
      showed oncocytic metaplasia of interlobular bile duct epithelium. We report that
      oncocytic metaplasia of bile duct epithelium is part of the pathological spectrum
      of hepatic GVHD.

PMID- 7581155
TI  - Reversal of severe hepatic veno-occlusive disease by combined plasma exchange and
      rt-PA treatment.
AB  - We report the successful treatment of a case of severe hepatic veno-occlusive
      disease (VOD) by combined treatment with exchange plasmapheresis and fibrinolysis
      with rt-PA. Very advanced alterations of hepatic vascular circulation, evaluated
      by Doppler sonography, reverted to normal after treatment. Severe VOD, defined by
      McDonald's criteria, produces a mortality of 98%. This case suggests that this
      new method of combined treatment might contribute to changing the usually bad
      prognosis of this clinical condition.

PMID- 7581158
TI  - Somatostatin for the treatment of upper gastrointestinal bleeding (UGIB) in
      patients undergoing autologous bone marrow transplantation (ABMT)

PMID- 7581157
TI  - Acute hemolysis during cyclosporine therapy successfully treated with vitamin E.
AB  - The immunosuppressant cyclosporine induces acute hemolysis (hemolytic uremic
      syndrome) in some patients after transplantation, possibly because of its effects
      on the vascular endothelium. We report a case of Coombs-negative, non-immune
      severe hemolytic anemia during cyclosporine therapy after allogeneic bone marrow
      transplantation for severe aplastic anemia. Uremia was not observed. Vitamin E
      was effective in treating the intravascular hemolysis.

PMID- 7581159
TI  - Aspergillosis prior to bone marrow transplantation. Infectious Diseases Working
      Party of the EBMT and the EORTC Invasive Fungal Infections Cooperative Group.

PMID- 7581161
TI  - Availability and appropriateness of allo-BMT for CML: the Italian experience.

PMID- 7581160
TI  - Filgrastim post-chemotherapy mobilizes more CD34+ cells compared to its use
      during steady-state haemopoiesis.

PMID- 7581162
TI  - Specific imaging of hormone-dependent mammary carcinoma in nude mice with [131I]
      anti-estriol 3-sulfate antibody.
AB  - We tried to put the estrogen metabolite to use in tumor imaging. The antibody
      against estriol 3-sulfate (E3 3-S), which was one of the major metabolites of
      estrogen in hormone-dependent mammary carcinoma, was prepared and the tissue
      distribution and imaging of human breast carcinoma with anti-E3 3-S antibody (Ab)
      were studied in nude mice. In hormone-dependent breast carcinoma, MCF-7,-bearing
      nude mice, [125I] anti-E3 3-S Ab localized in tumor with the percentage injected
      dose/g of 9.29 +/- 3.01 (mean +/- SD). This value was significantly high compared
      with that in hormone-independent breast carcinoma, MDA-MB-231,-bearing nude mice.
      At 72 h after the administration of [125I]anti-E3 3-S Ab to MCF-7 bearing mice,
      tumor/blood, tumor/liver and tumor/muscle ratios were 0.49, 5.02 and 6.83,
      respectively. These ratios were supposed to be enough for imaging. In
      radioimmunoscintigraphy, a MCF-7 tumor was clearly visualized at 120 or 168 h
      post-injection of [131I]anti-E3 3-S Ab.

PMID- 7581163
TI  - Radiolabeled metabolites of proteins play a critical role in radioactivity
      elimination from the liver.
AB  - We have recently reported that the behavior of radiolabeled metabolites in the
      liver appears to be responsible for the hepatic radioactivity levels after
      administration of protein radiopharmaceuticals. To better understand the role
      played by radiolabeled metabolites in hepatic radioactivity levels, two benzyl
      EDTA derivatives rendering different radiolabeled metabolites, 1-(4
      isothiocyanatobenzyl)ethylenediaminetetraacetic acid (SCN-Bz-EDTA) and 1-[p-(5
      maleimidopentyl)aminobenzyl]ethylenediaminetetraacetic acid (ECMS-Bz-EDTA), were
      selected as bifunctional chelating agents (BCAs), and 111In labeling of
      galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) was
      performed. Biodistribution of radioactivity in mice and subcellular distribution
      of radioactivity in hepatocytes were then compared. After accumulation in hepatic
      parenchymal cells, NGA-EMCS-Bz-EDTA-111In rendered a faster elimination rate of
      radioactivity from the liver than NGA-SCN-Bz-EDTA-111In. Although each 111In-NMA
      exhibited a delayed elimination rate of radioactivity from the liver compared to
      the 111In-NGA counterpart, NMA-EMCS-Bz-EDTA-111In showed faster elimination rate
      of radioactivity than NMA-SCN-Bz-EDTA-111In. Analyses of radioactivity excreted
      in feces and urine and remaining in the liver indicated that both BCAs rendered
      mono-amino acid adducts as the major radiolabeled metabolites (cysteine-EMCS-Bz
      EDTA-111In and lysine-SCN-Bz-EDTA-111In), which were generated in both cell types
      of the liver within 1 h postinjection. Subcellular distribution of radioactivity
      indicated that the radioactivity was copurified with lysosomes. These results
      demonstrate that although in vivo stability of radiometal chelates is essential,
      the biological properties of the radiolabeled metabolites generated after
      lysosomal proteolysis in hepatocytes play a critical role in radioactivity
      elimination from the liver.

PMID- 7581166
TI  - Synthesis, characterization and biodistribution of neutral and lipid-soluble
      99mTc-bisaminoethanethiol spiperone derivatives: possible ligands for receptor
      imaging with SPECT.
AB  - Using parts of the molecular structure of spiperone, two new ligand systems for
      complexation with [99mTc]technetium were prepared in order to develop potential
      receptor imaging agents for single photon emission computer tomography (SPECT).
      The bis-aminoethanethiols (BAT): 1-benzyl-4-(2-mercapto-2-methyl-4-aza-pentyl)-4
      (2-mercapto-2-methyl- propylamino)-piperidine (benzylpiperidyl-BAT, BP-BAT) and 1
      [3-(4-fluorobenzoyl)-propyl]-4-(2-mercapto-2-methyl-4-aza-pentyl)-4- (2-mercapto
      2-methyl-propyl-amino)-piperidine (butyrophenoylpiperidyl-BAT, BUP-BAT) form
      stable, neutral and lipid soluble complexes with [99mTc]technetium at pH > or =
      11 using SnCl2 as reducing agent in nearly quantitative radiochemical yields.
      Biodistribution of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed a moderate
      clearance from blood and low uptake and retention in the liver, whereas brain
      uptake was moderate, however with prolonged brain retention. On the other hand,
      significant accumulations and retentions were observed in heart, kidney and lung
      with increasing oxygen/blood ratios up to 24 h. Within 24 h p.i. 22 and 29% of
      the injected dose (i.d.) of 99mTc-BP-BAT and 99mTc-BUP-BAT were eliminated by
      hepatobiliary excretion whereas 22% i.d. of both 99mTc-BAT complexes were
      excreted into the urine. Although first biodistribution studies of 99mTc-BP-BAT
      and 99mTc-BUP-BAT in rats showed relatively low brain uptake, the high uptake in
      peripheral, receptor rich organs indicates that compounds of this type may be
      used as a basis for further structural modification to develop agents with
      optimal properties for cerebral or peripheral receptor imaging with SPECT.

PMID- 7581164
TI  - Mutant mouse strains as models for in vivo radiotracer evaluations:
      [11C]methoxytetrabenazine ([11C]MTBZ) in tottering mice.
AB  - The regional brain distribution of [11C]methoxytetrabenazine ([11C]MTBZ), a high
      affinity radioligand for the vesicular monoamine transporter, has been examined
      in normal and tottering mice, which are neurological mutants. The tottering mice
      show significantly higher radiotracer accumulation (150-195% of controls) in all
      brain regions examined (striatum, cortex, hippocampus, hypothalamus, cerebellum
      and thalamus). The increases in [11C]MTBZ binding correlate (r = 0.91) with the
      reported increases in norepinephrine concentrations in these regions, and are
      consistent with the noradrenergic hyperinnervation characteristic of the
      tottering mutant mouse. These studies demonstrate that a mutant mouse model of
      increased innervation can be used to evaluate the sensitivity of an in vivo
      radiotracer measure, in this case [11C]MTBZ binding to vesicular transporters, to
      an increase in the numbers of binding sites in specific regions of the brain.

PMID- 7581165
TI  - Biodistribution of monoclonal antibody Po66 in a human lung tumour-bearing mouse
      model: effect of blood exchange on tumour antibody uptake.
AB  - We report a method designed to improve the specificity of tumour uptake after
      intravenous injection of an anti-tumour monoclonal antibody (MAb). It consists in
      increasing the blood clearance of the MAb injected in order to diminish its
      tissue activity, without altering tumour binding. Po66, an MAb directed against
      lung squamous cell carcinoma, was radiolabelled with 125I and injected i.v. into
      tumour-bearing nude mice. Radioactivity uptake by the tumour reached a plateau on
      days 3-5 which persisted up to day 14 after antibody injection. The radiolabelled
      Po66 remaining in the circulation on day 5 after injection was removed by means
      of exsanguination and blood transfusion. This blood exchange technique depleted
      circulating radiolabelled MAb by 60%, whenever mice had been injected with Po66
      or an unrelated control IgG1. The proportion of radiolabelled Po66 taken up by
      the tumour 5 days after blood exchange did not differ substantially from that of
      non-exsanguinated controls (96.1% of controls). In contrast, there was a
      significant decrease in blood radioactivity (46% of control values on day 5).
      Blood exchange provoked a 1.8 fold increase in the tumour/blood and a 1.5-1.8
      fold increase of the tumour/organ radioactivity ratios. After injection of
      unrelated radiolabelled IgG1, blood exchange reduced by 50% both blood and tumour
      radioactivity, and did not increase the tumour/blood or tumour/organ ratios.
      Hence, removal of 60% of circulating Po66, 5 days after its injection, did not
      affect the binding or retention of the antibody by the tumour, but would probably
      constitute a marked improvement if the antibody is used for two-phase
      radioimmunotherapy.

PMID- 7581167
TI  - Synthesis, characterization and biodistribution of a new technetium-99m complex
      with trimethylsilylmethylisonitrile. Comparison with 99mTc-TBI and 99mTc-MIBI.
AB  - An isonitrile ligand with a silicium component was synthesized and a copper salt
      of this ligand was then used to form a 99mTc complex. We evaluated the
      physicochemical characteristics of the complex and its biodistribution in rat.
      The chemical properties, i.e. lipophilic affinity and charge, were comparable to
      those of other 99mTc complexes formed with similar isonitrile compounds (99mTc
      MIBI and 99mTc-TBI). In contrast, the tissue biodistribution of this new
      technetium complex differed markedly, as it was mainly taken up in the liver and
      not at all in the heart.

PMID- 7581168
TI  - Syntheses of several 99mTc and 131I labeled neoglycoalbumins and their
      differential uptake patterns in animal biodistribution experiments.
AB  - Several glycoconjugates, alpha-D-mannopyranosyl, beta-L-fucopyranosyl, alpha-L
      rhamnopyranosyl, beta-D-glucopyranosyl and beta-D-galactopyranosyl human serum
      albumin, were synthesized using C9-tether and radiolabeled with 99mTc and 131I.
      Both 99mTc and 131I radiolabeled neoglycoalbumins had considerable stability and
      exhibited similar biodistribution patterns within the experimental limits. The
      results of biodistribution studies can be explained from the in vitro
      observations that 99mTc-beta-D-galactopyranosyl albumin binds to hepatic binding
      protein in liver in a dose-dependent fashion. The radiolabeled glycoalbumins
      derived from D-mannopyranose and L-fucopyranose also bind in a dose-dependent
      fashion to the receptors present in the liver sinusoidal cells and spleen
      macrophages. The beta-D-glucopyranosyl and alpha-L-rhamnopyranosyl
      neoglycoalbumins accumulate nonspecifically in liver and spleen.

PMID- 7581170
TI  - Solid phase labeling of monoclonal antibodies with 99mTc using two bifunctional
      photocleavable reagents.
AB  - Two photolabile heterobifunctional O-nitrobenzyl reagents were used to modify
      B72.3 monoclonal antibody followed by immobilization on a solid support. Antibody
      was labeled with 99mTc and then cleaved from the resin on irradiation with light
      of peak intensity at 365 nm. The antibody was restored unmodified after cleavage.
      The labeled product, void of any impurity or free 99mTc, exhibited compatible
      imaging quality and biodistribution when compared to the same product labeled
      using solution chemistry. This new technique offers the potential of a
      commercially attractive 99Tc-labeling kit. Although the method was designed from
      the perspective of 99mTc-labeling of monoclonal antibodies, it should be
      applicable to any solid phase protein modification.

PMID- 7581169
TI  - Synthesis of radioiodinated naltrindole analogues: ligands for studies of delta
      opioid receptors.
AB  - Analogues of naltrindole and N1'-methylnaltrindole having radioiodine in the 7'
      position of the indole ring have been prepared for evaluation as delta opioid
      receptor ligands. The no-carrier-added radiosyntheses were conducted by Cu(I)
      assisted nucleophilic exchange of radioiodide for bromide under reducing
      conditions at 190 degrees C. A combination of HPLC and solid-phase extraction
      gave the 125I- or 123I-labeled products in satisfactory yields (47%) with high
      radiochemical purities (> 98%) and high specific activities (125I: 43-68
      GBq/mumol, 1155-1833 mCi/mumol; 123I: > 92 GBq/mumol, 2500 mCi/mumol).

PMID- 7581171
TI  - PET study of the distribution of [11C]fluoxetine in a monkey brain.
AB  - No-carrier-added [11C]fluoxetine (2) was synthesized by methylation of
      norfluoxetine (1) with [11C]H3I in 20% radiochemical yield in a synthesis time of
      40 min from EOB with a specific activity of 0.48 Ci/microM (EOB). In vivo study
      in mouse indicated that the uptake of 2 in mouse tissues was high and the
      radioactivity remained constant throughout the study. The uptake of 2 in mouse
      brain was 4%/g. PET study in a Rhesus monkey also showed that the uptakes of 2 in
      different brain regions were similar and the retention of radioactivity in these
      regions remained constant throughout the study (80 min). Analysis of arterial
      plasma by HPLC showed that only 20% of radioactivity in the plasma remained as 2
      at 30 min post-injection. These results suggest that the uptake of fluoxetine in
      monkey brain is probably not receptor mediated. Rather, blood flow, lipophilicity
      or other transport mechanisms may play a role in its uptake.

PMID- 7581172
TI  - Synthesis and characterization of [125I]N-(2-aminoethyl)-4-iodobenzamide as a
      selective monoamine oxidase B inhibitor.
AB  - We described the radiosynthesis of an analog of Ro 16-6491, [125I]N-(2
      aminoethyl)-4-iodobenzamide, for SPECT exploration of the monoamine oxidase B
      (MAO-B) in human brain. The radiolabelling was carried out by nucleophilic
      exchange of the brominated precursor at solid-state phase in presence of ammonium
      sulphate. The radiochemical purity of radioiodinated product was higher than 95%.
      In comparison with Ro 16-6491, the in vitro studies showed a good selectivity of
      stable N-(2-aminoethyl)-4-iodobenzamide for MAO-B but a slightly lower affinity.
      Biodistribution studies in the rat showed a high and selective uptake of this
      compound in the pineal gland 1 h after i.v. injection. The cerebral uptake was
      low, but the coupling of [125I]N-(2-aminoethyl)-4-iodobenzamide with a lipophilic
      radical to enhance the passage through the blood-brain barrier can be envisaged.

PMID- 7581173
TI  - BATO complexes derived from dimethoxy dioximes: synthesis, characterization and
      biodistribution.
AB  - To prepare less lipophilic BATO complexes, two new methoxy-substituted dioximes
      were synthesized: cis-4,5-dimethoxycyclohexane-1,2-dione dioxime (DMCDO) and 1,4
      dimethoxybutane-2,3-dione dioxime (DMDMG). 99mTcCl(DMCDO)3BMe (BMe =
      methylboronic acid) was prepared and characterized. Reversed-phase HPLC analyses
      of 99mTcCl(DMCDO)3BMe and 99mTcCl(DMCDO)3-p-TBA (p-TBA = p - tolylboronic acid)
      indicated that both of these complexes were mixtures of four enantiomeric pairs
      of diastereomers. Attempted preparation of a BATO complex from DMDMG gave a
      mixture of products. In rats, 99mTcCl(DMCDO)3BMe displayed more rapid liver and
      renal clearance than 99mTcCl(CDO)3BMe, but 99mTcCl(DMCDO)3BMe and 99mTcCl(DMCDO)3
      p-TBA displayed low uptake in both heart and brain.

PMID- 7581174
TI  - 6 alpha-[18F]fluoroprogesterone: synthesis via halofluorination-oxidation,
      receptor binding and tissue distribution.
AB  - We have evaluated 6 alpha-[18F]fluoroprogesterone as a potential imaging agent
      for progesterone receptor (PgR)-positive breast cancer. 6 alpha
      Fluoroprogesterone (1) was obtained via halofluorination of the C-5 double bond
      in pregnenolone, followed by oxidation of the 3 beta-OH group, elimination of HBr
      from C-4,5, and epimerization at the C-6 center. The relative binding affinity
      (RBA) of 6 alpha-fluoroprogesterone (1) to PgR is 11 (R5020 = 100), and its
      binding selectivity index (BSI, i.e. the ratio of the RBA to the non-specific
      binding, NSB) is 14.4; these values are similar to those of progesterone. 17
      alpha-Acetoxy-6 alpha-fluoroprogesterone (2) was also prepared by the same
      method, but was not used for fluorine-18 labeling studies because its binding
      affinity for PgR is very low (0.9). The synthesis of 1 was adapted to fluorine-18
      labeling and although the overall radiochemical yield was low (decay-corrected,
      0.3%), progestin [18F]1 was obtained in moderately high effective specific
      activity (147 Ci/mmol). In vivo distribution studies using estrogen-primed
      immature female rats showed that 6 alpha-fluoroprogesterone ([18F]1) has low
      uterine uptake, low target tissue selectivity, and high fat uptake, presumably
      due to its low RBA and BSI. High uptake in bone, which indicates extensive
      metabolic defluorination, suggests that the C-6 position of steroids may not be a
      good site for fluorine-18 labeling.

PMID- 7581175
TI  - Comparison of the infection imaging properties of a 99mTc labeled chemotactic
      peptide with 111In IgG.
AB  - The biodistribution and infection imaging properties of a 99mTc labeled hydrazino
      nicotinamide (HYNIC) derivatized chemotactic peptide analog (For-Met-Leu-Phe-Lys
      HYNIC) and 111In-DTPA-IgG were compared in rabbits with Escherichia coli
      infection. Six New Zealand white rabbits were injected in the left posterior
      thigh with a suspension of E. coli. Twenty four hours later, the animals were
      injected with: 1.0 mCi of 99mTc labeled peptide plus 0.1 mCi of 111In-DTPA-IgG.
      At 2-3 and 16-18 h, dual photon scintigrams were acquired and the images were
      corrected for crossover between the two windows. After recording the final
      images, the animals were sacrificed and biodistribution was determined. At both
      imaging times the biodistributions of the two reagents were markedly different.
      The highest concentrations of 111In-DTPA-IgG were detected in blood pool
      structures, liver and kidney. In contrast localization of 99mTc labeled peptide
      was greatest in spleen, lung and liver (consistent with binding to leukocytes).
      In general, the sites of infection were better visualized with the radiolabeled
      peptide and T/B ratios increased with time (P < 0.01). At both times, the T/Bs
      for 99mTc-peptide were higher (P < 0.01); 3.54 +/- 0.47 vs 2.52 +/- 0.38 at 2-3 h
      and 6.88 +/- 0.79 vs 3.78 +/- 0.36 at 16-18 h. These results indicate that
      although both radiopharmaceuticals localize at sites of infection, the
      radiolabeled peptide are superior reagents for the rapid detection of focal sites
      of infection. However, since the mechanisms of localization are different the
      combined use of both agents could have value in the general evaluation of
      infection/inflammation.

PMID- 7581176
TI  - Characterization of the dopamine transporter in nonhuman primate brain:
      homogenate binding, whole body imaging, and ex vivo autoradiography using [125I]
      and [123I]IPCIT.
AB  - IPCIT [2 beta-carboisopropoxy-3 beta-(4-iodophenyl)tropane; also designated RTI
      121] is the isopropyl ester of beta-CIT [2 beta-carbomethoxy-3 beta-(4
      iodophenyl) tropane]. Although beta-CIT binds to dopamine (DA), serotonin (5-HT)
      and norepinephrine (NE) transporters, IPCIT has been reported to be selective for
      the DA transporter. IPCIT was labeled with 125I and its receptor binding to
      membranes prepared from baboon striatum was compared with that of [125I] beta
      CIT. These studies confirmed the relative selectivity of IPCIT for the DA
      transporter in comparison to 5-HT and NE transporters. The nonspecific binding of
      [125I]IPCIT was almost four times greater than that of [125I] beta-CIT. The
      biodistribution of IPCIT was examined in two baboons with whole body imaging for
      24-30 h after administration of 3 mCi of 123I-labeled tracer. The brain uptake
      peaked within the first hour at 9.2% of the injected dose and the majority of
      activity in the body cleared through the hepatobiliary system. The distribution
      of activity within the brain was examined with ex vivo autoradiography in one
      monkey injected with [123I]IPCIT. Activity was concentrated in the caudate and
      putamen and had values of 5 and 7 microCi/cm3 per microCi/g, respectively. The
      distribution in brain regions receiving moderately dense serotonergic innervation
      (e.g. superior colliculus and thalamus) had levels of activity equivalent to that
      in cerebellum. This study confirmed the in vitro and in vivo selectivity of IPCIT
      for the DA transporter but also showed that [125I]IPCIT had higher in vitro
      nonspecific binding than [125I] beta-CIT.

PMID- 7581178
TI  - Solid-phase reversible trap for [11C]carbon dioxide using carbon molecular
      sieves.
AB  - A simple, maintenance-free trapping technique which concentrates and purifies no
      carrier-added 11CO2 from gas targets is described. The trap requires no liquid
      nitrogen cooling and has no moving parts besides solenoid valves. It employs
      carbon molecular sieves to adsorb 11CO2 selectively from gas targets at room
      temperature. Nitrogen, O2, CO, NO and moisture in the target gas which could
      interfere with subsequent radiochemical steps are not retained. Trapping
      efficiency of 1 g of sieve for 11CO2 from a 240 cm3 target gas dump and helium
      flush cycle is > 99%, and the adsorbed 11CO2 is recovered quantitatively as a
      small concentrated bolus from the carbon sieve trap by thermal desorption. This
      durable trap has performed reliably for more than 1 y with a single charge of
      carbon sieve. It has simplified the production, and improved the yields of
      several 11C-radiochemicals at this laboratory.

PMID- 7581177
TI  - Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl
      11C]iomazenil.
AB  - The central benzodiazepine receptor tracer [N-methyl-11C]iomazenil (Ro 16-0154)
      was synthesized by alkylation of the desmethyl precursor noriomazenil with
      [11C]methyl iodide. The [11C]CH3I (prepared by reduction of [11C]CO2 with LiA1H4
      followed by reaction with HI) was reacted with noriomazenil in N,N
      dimethylformamide and Bu4N+OH- for 1 min at 80 degrees C and purified by HPLC
      (C18, 34% CH3CN/H2O 7 mL/min). The product was obtained with synthesis time 35 +/
      5 min (mean +/- SD, n = 7), radiochemical yield (EOB) 36 +/- 16%, radiochemical
      purity 99 +/- 1%, and specific activity 5100 +/- 2800 mCi/mumol. Absorbed
      radiation doses were calculated from previously acquired human biodistribution
      data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8
      h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After
      i.v. injection of [11C]iomazenil in an adult baboon or healthy human volunteer,
      radioactivity accumulated in the cortex with time-activity curves in agreement
      with results obtained with [11C]flumazenil PET and [123I]iomazenil SPECT studies.
      The count rate was sufficient to obtain quantitative images up to 2 h post
      injection with a 14 mCi injection. These results suggest that [11C]iomazenil will
      be a useful agent for measuring benzodiazepine receptors in vivo by positron
      emission tomography.

PMID- 7581180
TI  - Comparison of the distribution of radioiodinated di- and tri
      hydroxyphenylethylene estrogens in the immature female rat.
AB  - The uptake, retention and tissue to blood ratios of two non-steroidal, 125I
      labeled iodoestrogens, an iodotrihydroxyphenylethylene, 2-iodo-1,2-bis(4
      hydroxyphenyl)-2-(3-hydroxyphenyl)ethylene and an iododihydroxyphenylethylene, 2
      iodo-1,1-bis(4-hydroxyphenyl)-2-phenylethylene, were compared after
      intraperitoneal injection in immature female rats. The
      iodotrihydroxyphenylethylene showed an unexpectedly prolonged specific retention
      in estrogen target tissue, lasting up to 72 h. It was rapidly cleared from blood
      and non-target tissues so that uterus or ovary to blood ratios of greater than
      100 were seen at 2 and 3 days. This iodotrihydroxyphenylethylene may have
      clinical potential for estrogen receptor-containing cancers.

PMID- 7581179
TI  - Radiosyntheses of labeled beta-pseudothymidine ([C-11]- and [H-3]methyl) and its
      biodistribution and metabolism in normal and tumored mice.
AB  - In order to develop labeled probes for measuring DNA synthetic rates in vivo we
      investigated [H-3]- and [C-11]methyl labeled beta-pseudothymidine (2a), and
      report on their radiosyntheses from methyl iodide. We find methylation is rapid
      and regioselective on N-1 of the acylurea moiety of 2'-deoxy-beta-D-pseudouridine
      (1a), in the presence of N,N-diisopropylethylamine and N,N-dimethylformamide at
      60 degrees C. Although yields are low (11% [C-11]-decay corrected and 4.4% [H
      3]), the method is simple and high specific activity tritiated methyl iodide can
      be used. In contrast to the rapid degradative de-glycosylation of thymidine in
      blood, beta-pseudothymidine is stable. However, based on biodistribution and
      metabolite studies, the anticipated uptake of [H-3]methyl-beta-pseudothymidine
      into mouse DNA of proliferating tissues (e.g. spleen, thymus and duodenum) and
      implanted tumors was not observed.

PMID- 7581181
TI  - Reliable preparation of 99mTc (V) DMSA by a simple modified method using a
      commercial kit for 99mTc (III) DMSA.
AB  - 99mTc pentavalent dimercaptosuccinic acid [99mTc (V) DMSA], a useful agent for
      imaging thyroid medullary carcinoma and other tumors, can be reliably prepared by
      addition of NaHCO3 and then Na99mTcO4 to a commercial kit for 99mTc trivalent
      DMSA [99mTc (III) DMSA], followed by bubbling oxygen through the solution for 10
      min. 99mTc (V) DMSA made by this method is radiochemically pure and stable for 24
      h, and it gives a rat biodistribution similar to that of the agent made by
      previous methods. Clinical biodistribution and radiation dosimetry studies are
      planned.

PMID- 7581182
TI  - A longitudinal study of associates at the National Library of Medicine, 1957
      1990.
AB  - The Associate Program at the National Library of Medicine (NLM) is the oldest
      postgraduate training program for health sciences librarians in the United
      States. Despite the program's longevity, few data have been collected about the
      educational background or subsequent careers of the NLM Associates. This article
      describes one such study. When the study was conducted in 1990, 130 Associates
      had participated in the program since its inception in 1957. This report
      characterizes the age, gender, and educational background of the group as they
      entered the Associate Program and describes their subsequent employment and
      geographic distribution. The large number of Associates who have worked in health
      sciences libraries since completing the program indicates how much these
      individuals have contributed to NLM and the field of health sciences
      librarianship, and it also illustrates the value of the Associate Program in
      recruiting recent library graduates to the profession.

PMID- 7581184
TI  - Implementing hospital library automation: the GaIN project. Georgia Interactive
      Network for Medical Information.
AB  - The GaIN (Georgia Interactive Network for Medical Information) Hospital
      Libraries' Local Automation Project was a one-year, grant-funded initiative to
      implement an integrated library system in three Georgia hospitals. The purpose of
      the project was to install the library systems, describe the steps in hospital
      library automation, and identify issues and barriers related to automation in
      small libraries. The participating hospitals included a small, a medium, and a
      large institution. The steps and time required for project implementation were
      documented in order to develop a decision checklist. Although library automation
      proved a desirable approach for improving collection accessibility, simplifying
      daily routines, and improving the library's image in the hospital, planners must
      be sure to consider equipment as well as software support, staffing for the
      conversion, and training of the library staff and end users.

PMID- 7581183
TI  - A systematic approach to finding answers over the Internet.
AB  - New users often are surprised at how chaotic the Internet appears. They have
      heard so much about it and then find that it is a jumble of menus and resources.
      Even so, it is possible to find answers to reference questions on the Internet.
      This paper outlines a method for doing so. The method involves five steps: gather
      information and tools, learn the terminology, assemble a manual, write a
      strategy, and make bookmarks. The paper offers medical reference scenarios that
      illustrate how to search a database, find a program, find a document, and telnet
      to another site on the Internet.

PMID- 7581186
TI  - Tomorrow's library: will it all be infrastructure?
AB  - The form in which knowledge is described and encapsulated has a major impact on
      the design of libraries and the functions performed within the library. Libraries
      as we known them have been primarily built to store and disseminate knowledge in
      book format. New technology and the changing needs of knowledge workers, which
      form important parts of the logocentric, practicentric, and democentric elements
      of our information infrastructure, have created profound changes in our culture,
      challenge our definition of knowledge, and necessitate flexible designs for our
      libraries. The invention of practical mediums for information access, such as the
      book in the seventeenth century, television in the twentieth century, and perhaps
      the Internet in the twenty-first century, open the door to self-education with
      little economic discrimination. New roles for libraries are emerging that require
      flexibility in building design for moving collections, services, functions, and
      equipment; restructuring staff organizations; introducing new services associated
      with new technology; eliminating unnecessary or nonaffordable services; and
      housing other institutional departments within the structure of the "new"
      library.

PMID- 7581187
TI  - From brick face to cyberspace.
AB  - This paper will discuss the library as a place, looking at the history of the
      library as a building or part of a building. It will briefly trace the
      development of health sciences libraries, enumerate standard sources for planning
      libraries, and consider whether or not the library as a place has a future.

PMID- 7581185
TI  - End-user search behaviors and their relationship to search effectiveness.
AB  - One hundred sixty-one MEDLINE searches conducted by third-year medical students
      were analyzed and evaluated to determine which search moves were used, whether
      those individual moves were effective, and whether there was a relationship
      between specific search behaviors and the effectiveness of the search strategy as
      a whole. The typical search included fourteen search statements, used seven terms
      or "limit" commands, and resulted in the display of eleven citations. The most
      common moves were selection of a database, entering single-word terms and free
      text term phrases, and combining sets of terms. Syntactic errors were also
      common. Overall, librarians judged the searches to be adequate, and students were
      quite satisfied with their own searches. However, librarians also identified many
      missed opportunities in the search strategies, including underutilization of the
      controlled vocabulary, subheadings, and synonyms for search concepts. No strong
      relationships were found between specific search behaviors and search
      effectiveness (as measured by the librarians' or students' evaluations).
      Implications of these findings for system design and user education are
      discussed.

PMID- 7581188
TI  - The building-planning process: tips from the UMAB experience. University of
      Maryland at Baltimore.
AB  - The University of Maryland at Baltimore (UMAB) is in the midst of planning a new
      health sciences library/information services building! The planning process for a
      new health sciences library is described, including the components of the process
      and the planning team. The UMAB planning experience, with thirteen tips for a
      successful process, are presented.

PMID- 7581189
TI  - Ergonomics in the electronic library.
AB  - New technologies are changing the face of information services and how those
      services are delivered. Libraries spend a great deal of time planning the
      hardware and software implementations of electronic information services, but the
      human factors are often overlooked. Computers and electronic tools have changed
      the nature of many librarians' daily work, creating new problems, including
      stress, fatigue, and cumulative trauma disorders. Ergonomic issues need to be
      considered when designing or redesigning facilities for electronic resources and
      services. Libraries can prevent some of the common problems that appear in the
      digital workplace by paying attention to basic ergonomic issues when designing
      workstations and work areas. Proper monitor placement, lighting, workstation
      setup, and seating prevent many of the common occupational problems associated
      with computers. Staff training will further reduce the likelihood of ergonomic
      problems in the electronic workplace.

PMID- 7581190
TI  - A new hospital library: a marketing opportunity.
AB  - A new or remodeled library presents a unique marketing opportunity for the
      hospital librarian. Furthermore, a well-designed library markets itself through
      its convenience, attractiveness, and ease of use. A marketing approach to library
      planning takes into account needs of users and of library staff and considers the
      librarian's relations with the architect as well as with hospital employees. This
      paper describes ways to combine library planning with marketing techniques and
      specifies aspects of the library that contribute to its good image.

PMID- 7581191
TI  - Technical scale and high-level detail: Vanderbilt's award-winning Eskind
      Biomedical Library.
AB  - With its opening in March 1994, the Annette and Irwin Eskind Biomedical Library
      at Vanderbilt University in Nashville, Tennessee, launched a new era at the
      university's medical center. The new building is the culmination of much effort,
      involving the time and talents of many dedicated individuals. Because of its
      advanced technological features and its modernistic design, the building might be
      regarded as a model library for the twenty-first century.

PMID- 7581193
TI  - An architect's perspective on contemporary academic library design.
AB  - The making of space and place (architecture) requires cultural and financial
      consent as to societal value. Standards and values about the academic library of
      the immediate future are not always shared by librarians and architects; however,
      architects and librarians do possess several shared perceptions. Among these
      shared perceptions are that print collections will remain a primary function of
      libraries for the foreseeable future, flexibility in shelving arrangements are
      essential, adjacencies must be fluid, floor-to-floor heights should be generous,
      compact shelving has become commonplace, print and electronic media must coexist,
      and technology has not reduced library space requirements. Experience reinforces
      the continuing and increasing significance of the library on college and
      university campuses.

PMID- 7581192
TI  - Building a digital library for the health sciences: information space
      complementing information place.
AB  - In 1990, the University of California, San Francisco, dedicated a new library to
      serve the faculty, staff, and students and to meet their academic information
      needs for several decades to come. Major environmental changes present new and
      additional information management challenges, which can effectively be handled
      only through the widespread use of computing and computing technologies. Over the
      next five years, a three-pronged strategy will be followed. We are refining the
      current physical, paper-based library through the continuous application of
      technology for modernization and functional improvement. At the same time, we
      have begun the planning, design, and implementation of a "free-standing" Digital
      Library of the Health Sciences, focusing on the innovative application of
      technology. To ensure complementarity and product integrity where the two
      libraries interface, we will look to technology to transform these separate
      entities into an eventual, integral whole.

PMID- 7581194
TI  - Thoughts on cooperation among biomedical libraries in Genoa, Italy.

PMID- 7581196
TI  - Commitment and concern: the sixtieth annual International Federation of Library
      Associations and Institutions meeting, Havana, Cuba, August 1994.

PMID- 7581197
TI  - Jana Bradley, Ph.D. Medical Library Association President 1995-1996.

PMID- 7581195
TI  - How physicians and biomedical scientists in India learn information-seeking
      skills.

PMID- 7581198
TI  - [Antigenic variation and the problem of vaccines against African trypanosomes].
AB  - African trypanosomes evade the immune response of their host through continuous
      changes of their major surface antigen, the VSG. This antigenic variation is
      achieved by either alternative activation of different expression sites for the
      VSG gene, or DNA rearrangements occurring within a given site. Several minor but
      invariant surface proteins have recently been characterized. This is especially
      the case for some surface receptors, which appear to be located in an
      invagination of the plasma membrane termed the flagellar pocket. These proteins
      may represent useful targets for new vaccination strategies.

PMID- 7581199
TI  - [Regulation of expression of genes coding for lipogenesis enzymes during
      development in the rat].
AB  - In vivo studies in the rat during the weaning period and in vitro studies on
      cultured cells have shown that nutriments and pancreatic hormones play a major
      role in lipogenic enzyme gene expression in liver and adipose tissue. Activation
      of lipogenic enzyme gene expression in liver and adipose tissue is dependent upon
      the increased supply of glucose and the concomitant hyperinsulinemia that occur
      after weaning. In contrast, an elevated supply of polyunsaturated or an increased
      plasma glucagon level prevent lipogenic enzyme gene expression in liver and
      adipose tissue. Glucose-6-phosphate seems to be the intracellular metabolite that
      mediates the transcriptional activation of lipogenic enzyme genes in response to
      glucose.

PMID- 7581200
TI  - [Development of the nervous system in Drosophila].
AB  - The formation of sense organs in Drosophila involves a series of choices, each of
      which depends on the co-ordinated activity of a small battery of genes. Two
      essential steps of this process have been extensively studied over the past few
      years: the determination of neural precursor cells, and their diversification. In
      both cases, the choices are dichotomous, and each choice reflects the fact that a
      specific control gene is or is not expressed. This principle is illustrated in
      the case of the genes "cut" and "poxn", the expression of which controls the type
      of sense organ that a given precursor will form.

PMID- 7581201
TI  - A literature survey of a hundred years of anatomic and functional lateral
      pterygoid muscle research.
AB  - Controversial topics that influence the etiology and the treatment of
      temporomandibular disorders include anatomy and function of the lateral pterygoid
      muscle, and the nature of the disc-muscle connection. To explore whether an
      agreement has been reached among researchers, a literature survey focusing on the
      structure, performance, and disc-muscle interface of the lateral pterygoid muscle
      was performed. Eighty-nine original research articles were identified in the
      Index Medicus information system from 1879 to 1994 by applying the keyword phrase
      "lateral pterygoid muscle." A majority of references (65%) identified two
      separate parts of the lateral pterygoid muscle as well as insertions into the
      disc, the capsule, and the condyle. Seventy-five percent of the articles agreed
      on three major functions. This literature survey revealed a consensus regarding
      anatomy, function, and disc connection among the majority of the researchers.
      However, diverging opinions were persistent and could be identified.

PMID- 7581203
TI  - Diagnostic subgroups of craniomandibular disorders. Part II: Symptom profiles.
AB  - An overview is given of the following four well-defined diagnostic subgroups of
      patients who have craniomandibular disorders: those with a mainly myogenous
      component; those with internal derangement with reduction; those with internal
      derangement without reduction; and those with osteoarthrosis. Although it was
      inevitable that the subgroups were not completely homogeneous, symptom profiles
      differed considerably. There even seemed to be reasons to distinguish two
      osteoarthrosis groups in future research. Although the identification of
      clinically significant factors in a given patient with craniomandibular disorders
      remains a difficult clinical task, the symptom profiles provide a framework that
      may give more insight into the background of the complaint and into possible
      contributing factors. The symptom profiles also provide the possibility of a more
      directed choice of treatment and a treatment evaluation that is more aimed at the
      specific characteristics of the subgroups. It therefore may be concluded that, to
      increase insight into craniomandibular disorders, the evaluation of diagnostic
      subgroups has to be preferred in the assessment of a heterogeneous group of
      patients with craniomandibular disorders.

PMID- 7581204
TI  - Pain-pressure threshold in human gingivae.
AB  - The pain-pressure threshold in human tissues such as muscles may be affected by
      the anatomic location of the recording site and the rate of applied pressure.
      However, it is uncertain how these variables affect the pain-pressure threshold
      in healthy oral tissues. In 10 subjects, a custom-made algometer was used to
      apply pressure at a constant rate to 12 sites on the attached gingivae apical to
      teeth 11 to 16 and 41 to 46. The pain-pressure threshold was measured at three
      different rates of applied pressure at weekly intervals for 4 weeks. The pain
      pressure threshold was consistently higher at maxillary recording sites. There
      were, however, no differences in the pain-pressure threshold at different
      recording sites along the tooth row in the maxilla or mandible. The pain-pressure
      threshold measurements were consistent between recording sessions. The pain
      pressure threshold was affected by the rate of pressure application and appeared
      to increase linearly with increasing rate. This suggests that the pain-pressure
      threshold may be measured consistently in attached human gingivae. When
      measurement of deep sensation in the oral mucosa is planned, the location of the
      recording site and the rate of applied pressure should be verified.

PMID- 7581202
TI  - Diagnostic subgroups of craniomandibular disorders. Part I: Self-report data and
      clinical findings.
AB  - An overview is given of the most commonly investigated signs and symptoms
      associated with craniomandibular disorders as detected in a population of
      patients with craniomandibular disorders and in four defined diagnostic
      subgroups. The information was collected with a questionnaire and during an
      extensive clinical examination. Comparison of self-report and clinical data
      indicated that these two methods reveal different aspects of the patient's
      complaints and should be interpreted in their own way. The results showed that no
      statistically significant differences could be found between the four diagnostic
      subgroups with respect to occlusal factors, trauma, and clinically assessed
      parafunctional habits. The groups differed considerably with respect to general
      characteristics, pain variables, signs of craniomandibular disorders, self
      reported para-functional habits, psychosocial factors, and general health
      factors. However, despite the reduction in clinical characteristics of the four
      subgroups, there was little reduction in the diversity of factors associated with
      craniomandibular disorders. This implicates that almost all factors associated
      with craniomandibular disorders may influence the initiation and perpetuation of
      the different disorders in the individual patient, and therefore, remain of
      interest in future research.

PMID- 7581205
TI  - Stress, anticipatory stress, and psychologic measures related to sleep bruxism.
AB  - This study examined (1) the relationships between electromyographic-measured
      nocturnal bruxism, self-reported stress, and several personality variables, and
      (2) the relationship between belief in a stress-bruxism relationship and self
      reported stress. One hundred adult bruxers completed a battery of personality
      questionnaires, indicated whether they believed in a stress-bruxism relationship,
      presented for a dental examination, and had dental impressions taken.
      Subsequently, electromyographic measurements of bruxing frequency and duration
      were recorded for fifteen consecutive nights. Prior to each night's measurements,
      subjects indicated their levels of stress for the immediately preceding 24 hours.
      No overall relationship was established between electromyographic measures and
      the personality variables nor between electromyographic measures and self
      reported stress. Correlations between electromyographic measures and self
      reported stress were statistically significant for eight individual subjects.
      Further, subjects with high levels of stress reported more anxiety, irritability,
      and depression, and less denial. Subjects who believed in a stress-bruxism
      relationship reported greater stress.

PMID- 7581208
TI  - Clinical diagnosis of orofacial pain: impact of recent FDA ruling on electronic
      devices.

PMID- 7581206
TI  - Pain-related limitation in activities of daily living in patients with chronic
      orofacial pain: psychometric properties of a disability index.
AB  - Pain-related limitations in activities of daily living are presented for 272
      patients reporting orofacial pain of the temporomandibular region using the seven
      item Pain Disability Index. Results showed that the factor structure for
      orofacial pain patients differed little from the factor structure for outpatients
      visiting chronic pain clinic settings. Analysis of pain diagnostic subgroups
      showed that patients suffering myogenous complaints had higher scores for four of
      seven daily-living activities that involved pain-related limitations than
      patients suffering discal disorders. The factor analytical findings indicated
      that these patients share common pain-related limitations in activities of daily
      living. These findings are also consistent with previous results indicating
      greater pain in orofacial pain patients diagnosed with pain complaints primarily
      myogenous in origin than in pain patients having discal disorders.

PMID- 7581207
TI  - Characteristics of masticatory movements and velocity in children with juvenile
      chronic arthritis.
AB  - Oral motor function (mandibular displacement and velocity) in individuals with
      juvenile chronic arthritis was studied by using an optoelectronic method. The
      children were compared with two asymptomatic groups: one group with Class I
      occlusion and the other with Class II malocclusion. The results showed that
      children with juvenile chronic arthritis and condylar lesions had reduced lateral
      mandibular masticatory movements. In children with Class II malocclusion, a
      longer three-dimensional closing distance and a slower closing velocity were
      found. In children with both juvenile chronic arthritis and Class II
      malocclusion, an interaction between juvenile chronic arthritis and malocclusion
      resulted in a longer occlusal time, a shorter amplitude, and a slower velocity.
      It can be concluded that juvenile chronic arthritis and Class II malocclusion,
      per se, might have minor influences on the chewing characteristics, but the two
      factors seem to interact, resulting in an altered masticatory pattern. A possible
      explanation is that children with juvenile chronic arthritis have an increased
      risk of developing a Class II malocclusion because of the growth disturbances
      sequelae of condylar lesions. The alteration in occlusion, together with
      restricted movements in the arthritic condyle, may be the underlying reasons for
      the findings.

PMID- 7581209
TI  - Occlusion, Orthodontic treatment, and temporomandibular disorders: a review.
AB  - A review of the current literature regarding the interaction of morphologic and
      functional occlusal factors relative to TMD indicates that there is a relatively
      low association of occlusal factors in characterizing TMD. Skeletal anterior open
      bite, overjets greater than 6 to 7 mm, retruded cuspal position/intercuspal
      position slides greater than 4 mm, unilateral lingual crossbite, and five or more
      missing posterior teeth are the five occlusal features that have been associated
      with specific diagnostic groups of TMD conditions. The first three factors often
      are associated with TMJ arthropathies and may be the result of osseous or
      ligamentous changes within the temporomandibular articulation. With regard to the
      relationship of orthodontic treatment to TMD, the current literature indicates
      that orthodontic treatment performed during adolescence generally does not
      increase or decrease the odds of developing TMD later in life. There is no
      elevated risk of TMD associated with any particular type of orthodontic mechanics
      or with extraction protocols. Although a stable occlusion is a reasonable
      orthodontic treatment goal, not achieving a specific gnathologically ideal
      occlusion does not result in TMD signs and symptoms. Thus, according to the
      existing literature, the relationship of TMD to occlusion and orthodontic
      treatment is minor. Signs and symptoms of TMD occur in healthy individuals and
      increase with age, particularly during adolescence; thus, TM disorders that
      originate during various types of dental treatment may not be related to the
      treatment but may be a naturally occurring phenomenon.

PMID- 7581210
TI  - Lateral pterygoid muscle and the temporomandibular disc.
AB  - This anatomic study examines the attachment of the lateral pterygoid muscle to
      the capsule and disc of the temporomandibular joint. The anatomy of the
      temporomandibular joint and its surroundings, in particular the insertion of the
      superior head of the lateral pterygoid muscle, was studied by dissection and
      conventional histologic techniques. The material consisted of 16 cadaver
      specimens from individuals 60 years or older. The results showed that only a part
      of the superior head of the lateral pterygoid muscle is attached to the anterior
      portion of the capsule, which, in turn, is firmly attached to the disc, giving
      the impression that the muscle and the disc are directly connected. All specimens
      showed attachment of the superior head of the lateral pterygoid muscle to the
      anterior medial portion of the capsule, but they showed varying degrees of
      attachment to the lateral aspect of the temporomandibular joint capsule. The
      remaining part of the superior head of the lateral pterygoid muscle attached to
      the mandibular condyle. Serial sectioning in no instance showed direct insertion
      into the disc of the fibers of the superior head of the lateral pterygoid muscle.

PMID- 7581211
TI  - Statement on poliomyelitis vaccination for international travellers (evidence
      based medicine recommendations). Committee to Advise on Tropical Medicine and
      Travel (CATMAT).

PMID- 7581212
TI  - Travel statement on jet lag. Committee to Advise on Tropical Medicine and Travel
      (CATMAT).

PMID- 7581213
TI  - Outbreak of Campylobacter infection among farm workers: an occupational hazard.

PMID- 7581214
TI  - Resistance to quinolones among Campylobacter species--Ontario.

PMID- 7581218
TI  - The role of pharmacists in the recruitment of a cohort for postmarketing
      surveillance. A case study of acitretin in The Netherlands.
AB  - In October 1990, a recall procedure was issued regarding the drug acitretin. The
      recommended post-therapy contraception period after acitretin therapy was
      extended from 2 months to 2 years. For a postmarketing surveillance study, we
      recruited a cohort from the source population of women aged 15-45 years who were
      exposed to acitretin. Recruitment occurred through dermatologists, and
      pharmacists plus dispensing general practitioners. We describe the speed of and
      the response to the recruitment procedures, and the representativeness of the
      recruited cohort. We also studied whether the individuals who gave informed
      consent would have preferred to be recruited by either dermatologists or
      pharmacists, and whether the information obtained from pharmacists and dispensing
      general practitioners was valid. This study revealed that pharmacists and
      dispensing general practitioners (drug dispensers) recruited their subjects
      rapidly, with no or little selection; they attained a 42% response.
      Dermatologists recruited their subjects slowly and selectively; they attained a
      24% response. The majority of women (60%) recruited by dermatologists would have
      given their informed consent if they would have been recruited by their
      pharmacists. Drug dispensers are essential contributors to the recruitment of a
      study population. We do advise that such recruitment for a postmarketing
      surveillance study occurs by means of a collaboration between pharmacists and
      physicians.

PMID- 7581215
TI  - Traditional Chinese herbal medicine.
AB  - Herbal medicine, acupuncture and moxibustion, and massage are the three major
      constituent parts of traditional Chinese medicine. Although acupuncture is well
      known in many Western countries, Chinese herbal medicine, the most important part
      of traditional Chinese medicine, is less well known in the West. This article
      gives a brief introduction to the written history, theory, and teaching of
      Chinese herbal medicine in China. It also describes modern scientific research
      into and the quality control of Chinese herbal medicines in China. Some examples
      of how new drugs derived from Chinese herbs have been developed on the basis of
      traditional therapeutic experience are presented. Finally, the situation of
      Chinese herbal medicine in the West is discussed.

PMID- 7581216
TI  - Biosynthesis of pseudoisoeugenols in tissue cultures of Pimpinella anisum.
      Phenylalanine ammonia lyase and cinnamic acid 4-hydroxylase activities.
AB  - The genus Pimpinella contains pseudoisoeugenols, phenylpropanoids with a rare 2,5
      dioxy substitution pattern on the phenyl ring. To study the biosynthesis of these
      compounds, we set up a leaf-differentiating tissue culture of Pimpinella anisum.
      These cultures mainly produce epoxy-pseudoisoeugenol-(2-methylbutyrate). To
      corroborate the biosynthetic pathway of epoxy-pseudoisoeugenol-(2-methylbutyrate)
      as proposed on the basis of investigations with 13C/14C-labelled precursors, the
      key steps of the pathway were investigated at an enzyme level. Experiments with
      cell-free homogenates clearly revealed that L-phenylalanine is converted to (E)
      cinnamic acid by phenylalanine ammonia lyase and that (E)-cinnamic acid is
      converted to p-coumaric acid by cinnamic acid 4-hydroxylase. L-2-aminooxy-3
      phenylpropionic acid, an analogue of L-phenylalanine, inhibited the incorporation
      of L-[3'-13C]phenylalanine into epoxy-pseudoisoeugenol-(2-methylbutyrate). Up to
      2% of the precursor DL-[3'-13C]phenyllactate was incorporated into epoxy
      pseudoisoeugenol-(2-methylbutyrate). Inhibition experiments with oxalacetic acid
      clearly showed that cinnamic acid is not formed by dehydration of phenyllactic
      acid in this leaf-differentiating tissue culture of P. anisum.

PMID- 7581217
TI  - Synthesis and pharmacology of a series of new organic nitrate esters.
AB  - New organic nitrate esters, derived from structurally different (cyclo)aliphatic
      templates, were synthesized and pharmacologically investigated. Their in vitro
      vascular smooth muscle relaxing activities and, occasionally, in vivo
      haemodynamic profiles were studied and compared to those of the clinically
      important nitrates, glyceryl trinitrate, isosorbide dinitrate and isosorbide-5
      mononitrate. A number of compounds appeared to be even more potent than glyceryl
      trinitrate. Qualitative structure-activity relationships within the series of new
      compounds are discussed. In flexible n-alkylene dinitrates, lipophilicity as well
      as chain length appears to affect in vitro activity. In semi-rigid cyclohexylene
      dinitrates, the number of atoms between and the configuration of the nitrate
      groups may play an important role. Finally, in cycloalkylene mononitrates neither
      the number of ring carbon atoms nor the lipophilicity clearly affects the in
      vitro activity. It is suggested that, apart from a limited involvement of
      compound lipophilicity, other factors such as differences in enzymatic conversion
      to a common putative bioactive species, nitric oxide, are responsible for the
      observed differences in activity.

PMID- 7581219
TI  - Bromocriptine and suppression of postpartum lactation. The incidence of adverse
      cardiovascular effects in women of child-bearing age.
AB  - The use of bromocriptine for the suppression of postpartum lactation drew
      widespread attention to a potentially increased risk for cardiovascular and
      cerebrovascular adverse effects. To estimate the incidence of these events a
      follow-up study was performed among 2,130 women of 15-44 years of age who were
      treated with a course of bromocriptine in 1990-1992. None of these women were
      admitted to the hospital for cardiovascular or cerebrovascular events. However,
      the incidence of pregnancy hypertension and the use of cardiovascular drugs
      increased considerably in the last 2 months before delivery. Therefore,
      cardiovascular or cerebrovascular events can probably be explained by pre
      existing morbidity rather than by the use of bromocriptine. We estimated, using a
      'worst-case' analysis, that fewer than 2 Dutch women each year would develop
      serious cardiovascular or cerebrovascular events.

PMID- 7581221
TI  - Bromocriptine and lactation suppression: are the risks acceptable?

PMID- 7581220
TI  - Epidemiological study of epilepsy by monitoring prescriptions of antiepileptic
      drugs.
AB  - The aim of this study is to evaluate a simple and effective method of acquiring
      epidemiological information about epilepsy. Data on antiepileptic drug
      prescriptions was collected, the utilization pattern being based on defined daily
      doses (DDDs). Antiepileptic drugs are epidemiological tracers of epilepsy due to
      their chronic and highly specific usage. Consequently, a prevalence rate for the
      whole population may be obtained by using DDDs. Data on antiepileptic drug
      prescriptions for a period of 6 months in 1992 and 6 months in 1993 indicate a
      utilization of approximately 7 DDDs of antiepileptic drugs per 1,000 inhabitants.
      The prevalence of epilepsy was estimated by correcting the exposure calculated in
      DDDs by a factor of 0.68. In our sample, the prevalence of the disease was 5.2
      per 1,000 inhabitants in 1992 and 4.9 per 1,000 in 1993. Physician prescriptions
      were concentrated on four compounds, namely phenobarbital, carbamazepine,
      valproic acid and phenytoin, which together represented 90% of total
      antiepileptic drug prescriptions.

PMID- 7581223
TI  - Effect of extracellular matrix proteins on vascular smooth muscle cell phenotype.
AB  - The effect on phenotypic expression of rabbit vascular smooth muscle cells (SMC)
      of the interstitial matrix proteins collagen I and fibronectin, the basal lamina
      proteins collagen IV and laminin, and the serum adhesion protein vitronectin was
      examined in culture. Experiments were performed in foetal calf serum stripped of
      fibronectin and vitronectin to eliminate their confounding effects. All the
      proteins promoted adhesion to the plastic culture dish (in a concentration
      dependent manner) of SMC freshly isolated from the artery wall. These cells had a
      high volume density of myofilaments (Vvmyo) in their cytoplasm. Laminin was best
      at maintaining SMC with a high Vvmyo (Vvmyo = 49.8%) followed by collagen IV
      (41.7%). Cells plated on vitronectin showed the lowest Vvmyo (31.3%). The results
      support the concept that the SMC basal lamina has a role in maintaining cells in
      the high Vvmyo phenotype.

PMID- 7581222
TI  - Practical strategies for the appropriate use of antimicrobials.
AB  - The use and misuse of antimicrobial agents is well documented in the literature.
      A variety of mechanisms has been used to enhance the appropriate use of these
      agents. A widely used initial strategy is the formation of multidisciplinary
      groups, such as Pharmacy and Therapeutics Committees or antimicrobial
      subcommittees, which are responsible for all antimicrobial policies for the
      health-care facility. Other techniques include the use of antimicrobial order
      sheets, automatic stop orders, therapeutic substitution, antibiotic restriction
      systems, and the use of selective antimicrobial susceptibility reporting systems.
      Many of these strategies have been reported to be effective in the management of
      antimicrobial usage; however, they also result in increased administrative and
      monitoring costs. Antimicrobial control systems must be individualized to the
      health-care facility.

PMID- 7581224
TI  - Transfection of normal human skin fibroblasts with human alpha 1(I) and alpha
      2(I) collagen gene constructs and evidence for their coordinate expression.
AB  - Type I collagen is composed of two alpha 1(I) chains and one alpha 2(I) chain
      that together form a unique triple helical structure. The genes for these chains
      are located on different chromosomes but their expression is tightly regulated.
      In order to investigate the mechanism of regulation of coordinate expression of
      these genes. I examined conditions for the efficient transfection of normal human
      skin fibroblasts with luciferase reporter gene constructs containing noncoding
      region of the first exon and the upper 500 base pairs sequence of the alpha 1(I)
      or alpha 2(I) gene. Expression ratio of these two reporter gene constructs was
      two to one, indicating these regions of alpha 1(I) and alpha 2(I) genes contain
      essential regulatory elements for the coordinate expression of alpha 1(I) and
      alpha 2(I) genes located on different chromosomes.

PMID- 7581225
TI  - Effect of microtubule-specific drugs upon spatial organization of extracellular
      matrix in fibroblastic cultures.
AB  - The aim of this investigation was to study the effects of microtubule-specific
      drugs, taxol and colcemid, on the distribution of cell-associated extracellular
      matrix in dense cultures of fibroblasts. Immunomorphological examination of human
      seven-day cultures revealed a dense network of fibronectin and tenascin matrix
      filaments preferentially oriented in parallel with the long axes of cell bodies.
      Depolymerization of the microtubular system by colcemid and its disorganization
      by taxol led to rapid and drastic changes in the organization of matrix network:
      fibronectin and tenascin filaments became disordered and, in particular, lost any
      orientation. These data show that the microtubular system controls the
      morphological organization, not only of intracellular cytoskeletal systems, but
      also of extracellular matrix structures.

PMID- 7581226
TI  - Distribution of acetylated tubulin in cultured cells and tissues from the
      Atlantic cod (Gadus morhua). Role of acetylation in cold adaptation and drug
      stability.
AB  - The Atlantic cod (Gadus morhua) is a poikilothermic animal living at temperatures
      between 2-15 degrees C. Isolated cod brain tubulin is, in contrast to mammalian
      brain tubulin, posttranslationally modified by acetylation to a high extent. To
      investigate the role of acetylation in cold adaptation, microtubules were
      isolated by a taxol-dependent procedure from different organs of the cod, and
      cells from different tissues were cultured. All cells from skin and brain were
      able to grow between 4 degrees C and room temperature. Microtubules in the
      cultured cells were sometimes severed near the periphery of the cells.
      Microtubules in brain cells were in general more stable to vinblastine and
      colchicine, when compared to skin cells. Acetylated microtubules were found only
      in brain cells, in peripheral nerves on scales and in nerves of the intestinal
      tract and in microtubules isolated from neuronal tissue. Our results show that
      acetylated microtubules are found both in the central and peripheral nervous
      system, but that there is no correlation between acetylation and cold-adaptation.

PMID- 7581227
TI  - The subcellular localization of newly synthesized cytochrome b5.
AB  - The fate of newly synthesized cytochrome b5 was studied in rat hepatocytes. Using
      an antibody specific for microsomal cytochrome b5, we found newly synthesized
      microsomal cytochrome b5 in both mitochondria and a mitochondria associated
      membrane fraction as well as in microsomes. Newly synthesized cytochrome b5 was
      quickly removed from the site of synthesis on free ribosomes and inserted into
      membranes at random. No migration of newly synthesized cytochrome b5 between
      cellular compartments was observed and therefore the assembly of the apoprotein
      with the heme moiety is apparently not taking place in any particular cellular
      compartment.

PMID- 7581228
TI  - Cell cycle-dependent morphological changes in the actin cytoskeleton induced by
      agents which elevate cyclic AMP.
AB  - Agents which increase the intracellular concentration of cyclic adenosine-5'
      monophosphate, induce a highly arborised morphology in a proportion of sub
      confluent Swiss 3T3 fibroblasts. During this process the organisation of actin
      filaments progressively changes from a characteristic stress fibre pattern to
      leave a network of actin filaments within each and every arborisation. Despite
      this massive reorganisation of the actin cytoskeleton no changes are observed in
      the extent of polymerisation of actin during arborisation. The proportion of
      cells in asynchronous cultures undergoing arborisation at maximal concentrations
      of agents reaches a maximum of 30%; suggesting that the effect might be mediated
      only in cells during a restricted period of the cell cycle. More than 80% of
      serum-starved cells responded to these agents between 1 and 8 hours after
      readdition of serum, but not at other times, suggesting that the arborisation
      response can occur only in the G1 phase of the cell cycle.

PMID- 7581230
TI  - Combined application of in vivo UV-crosslinking and in vitro label transfer in
      the examination of AU-rich sequence binding protein-RNA interactions.
AB  - A combination of in vivo UV light-induced crosslinking of nucleic acids to
      proteins and in vitro label transfer assay was applied to investigate specific
      interactions between AU-rich sequences (ARE) in the 3' UTR of lymphokine mRNAs
      and cytoplasmic AU-rich sequence element binding proteins (AUBP) in normal human
      lymphoblasts and MLA 144 gibbon lymphoid tumor cells. We demonstrate that a pool
      of cytoplasmic AUBP can be effectively crosslinked to RNA in vivo, suggesting a
      close association of these proteins with ARE sequences in the cytoplasm. We also
      show that the UV-crosslinked AUBP pool is markedly reduced in malignantly
      transformed MLA 144 cells compared with normal lymphoblasts, indicating weaker
      interaction between lymphokine ARE and AUBP in these tumor cells. Similar
      differences in AUBP-RNA associations were found between the membrane-bound
      polysomal subfractions of the two cell types where most of the AUBP activity was
      localized. We suggest that the decreased AUBP-mRNA association in MLA 144 cells
      might reflect a process concerned with disturbances of mRNA metabolism in the
      neoplastic phenotype.

PMID- 7581231
TI  - Normal transport of glutathione S-conjugates in erythrocytes of a patient with
      the Rhnull phenotype.

PMID- 7581229
TI  - Asymmetric cell division in human leukemic promyelocytic cells (HL-60).
AB  - Small cells accounted for 8-9% of the human leukemic promyelocytic cells (HL-60).
      The diameter of the small cells was 8.44 microns, whereas that of the large
      cells, which were heterogeneous in cells size, was 11.0 microns. The small cells
      were produced from the large cells through asymmetric cell division, which was
      demonstrated by cloning experiments and by microscopy.

PMID- 7581232
TI  - The status of undergraduate implant education in dental schools outside the
      United States.
AB  - Over the past 20 years the incorporation of implant dentistry into academia has
      been documented in some detail for North American dental schools but has not been
      pursued on an international level. In June of 1993, we surveyed 51 dental schools
      outside of the United States affiliated with the University of Pennsylvania
      School of Dental Medicine's Office of International Relations concerning their
      teaching involvement with implant dentistry. Results from the 44 (86 percent)
      responding schools suggest that implant dentistry is being incorporated into
      predoctoral curriculums. Industrialized countries were more inclined to provide
      implant education. Insufficient time and the thought that the predoctoral level
      was not the place for implant dentistry were cited as some of the reasons for not
      incorporating implant dentistry into the curriculum. Oral surgery,
      prosthodontics, and periodontics departments developed and administered the
      implant curriculum. Formats varied among schools with respect to allotted time,
      curricular placement, laboratory experience, and clinical participation. Didactic
      material most frequently presented included a historical overview, diagnosis and
      treatment planning, classification of dental implants, and surgical and
      prosthetic concepts. Clinical involvement varied from actual implant placement to
      observation of prosthodontic procedures. Results were categorized based on the
      TOEFL (Test of English as a Foreign Language) classification of countries in six
      regions.

PMID- 7581233
TI  - Reconstruction of the head and neck cancer patient with a vascularized fibula
      flap and dental implants: preliminary clinical report.
AB  - Reconstruction and rehabilitation of the head and neck cancer patient is
      challenging. Vascularized fibula grafts can be used to reconstruct mandibular
      defects after resection of the malignancy and the surrounding bone. Prosthodontic
      treatment can restore function and esthetics. This preliminary report discusses
      the use of endosseous implants in radiated mandibular vascularized fibula grafts
      after surgical resection.

PMID- 7581234
TI  - Implants from an orthodontic perspective.

PMID- 7581235
TI  - Use of an optical comparator for radiographic measurement of bone loss around
      endosseous implants: a pilot study.
AB  - A technique for the measurement of bone loss around endosseous implants using an
      optical comparator was investigated. Five operators were asked to measure the
      mesial and distal alveolar bone levels around a screw type dental implant on a
      periapical radiograph mounted on an optical comparator. The known size of a
      threaded implant was used as a reference. The bone loss around the implant was
      calculated by taking the average of the mesial and distal measurements.
      Statistical analysis at the 95 percent confidence level demonstrated that there
      was no significant difference among the measurements. Although the initial
      results are encouraging, additional research is necessary with a larger sample
      size to validate the accuracy of optical comparator readings and compare the
      efficacy of this technique with other currently used methods for determining bone
      loss around root form implants.

PMID- 7581236
TI  - The abutment transfer driver: a prosthodontic implant adjunct.
AB  - Rapid, accurate seating and cementation of permanent implant abutment heads that
      have been substantially altered for interocclusal clearance or parallelism
      requirements can be accomplished with individual, custom cast, insertion devices.
      The evolution and design of these devices (abutment transfer drivers) for fixed
      and removable prostheses are described.

PMID- 7581237
TI  - Connecting implant framework segments.
AB  - Indexing and soldering an implant bar can be a troublesome procedure. The
      expansion of the soldering investment may result in an inaccurate fit of the
      implant framework over the abutments or the implant heads. To overcome the
      distortion of the implant framework during soldering, a simple procedure for
      connecting the implant framework parts is described where the connector joints
      are cast-to rather than soldered.

PMID- 7581238
TI  - Alterations of alpha 1-adrenergic receptor densities in right and left ventricles
      of spontaneously hypertensive rats.
AB  - To clarify whether alpha 1-adrenergic receptors contribute to cardiac
      hypertrophy, we examined alpha 1-adrenergic receptor densities in the right and
      left ventricles of 5- and 20-week-old spontaneously hypertensive rats (SHR) and
      Wistar Kyoto rats (WKY) using [3H]prazosin. Also, we analyzed a pharmacologically
      distinct subtype of alpha 1-adrenergic receptors by pretreatment with
      chloroethylclonidine. The ratio of right ventricular weight to body weight as
      well as left ventricular weight to body weight was higher in SHR than in WKY at 5
      weeks of age. At 20 weeks of age, only the left ventricular weight to body weight
      ratio was higher in SHR. At 5 weeks of age, the right and left ventricular alpha
      1-adrenergic receptor densities in SHR were greater than those in WKY (LV 1760
      vs. 1275, RV 2543 vs. 1521 fmol/mg protein). At 20 weeks of age, only right
      ventricular alpha 1-adrenergic receptor density remained higher in SHR (1425 vs.
      885 fmol/mg protein). The percentage of pharmacologically distinct alpha 1A
      receptor was higher in the right ventricle of SHR than in that of WKY at 5 weeks
      of age (25% vs. 18%). There were no significant differences in the dissociation
      constants among the alpha 1-adrenergic receptor assays. These findings suggest
      that an increase in alpha 1-adrenergic receptors might be involved in cardiac
      hypertrophy in the early phase of hypertension in SHR.

PMID- 7581239
TI  - Effect of tea (Camellia sinensis L.) on lipid peroxidation in rat liver and
      kidney: a comparison of green and black tea feeding.
AB  - The antioxidant effects in the liver and kidney obtained from rat fed diets
      containing 3% green or black tea leaf powder, which were prepared from the same
      lot tea leaves, were studied using the tissue slice-antioxidant evaluation method
      with two lipid peroxidation inducers. After 50 d on the diets, liver slices
      prepared from green and black tea-supplemented rats showed significant inhibitory
      effects against tert-butyl hydroperoxide-induced lipid peroxidation. These
      effects, however, were not proportional to the amounts of (-)-epicatechins and
      antioxidant vitamins in the tea leaves. In the kidney, the antioxidant effect was
      observed only in the green tea-fed group. A similar antioxidant effect on the
      kidney was observed after oral administration of a major tea polyphenol, (-)
      epigallocatechin gallate (50 mg/kg body weight for 7 d). Liver slices from black
      tea-fed rats also inhibited bromotrichloromethane-induced lipid peroxidation.
      These results demonstrated that dietary green and black tea had antioxidant
      effects on tissue lipid peroxidation ex vivo.

PMID- 7581240
TI  - Lanosterol 14 alpha-demethylase (cytochrome P-45014DM): modulation of its enzyme
      activity by cholesterol feeding.
AB  - Regulation of the activity of lanosterol 14 alpha-demethylase (cytochrome P
      45014DM) by dietary cholesterol was studied in rats. In male rats fed a 3%
      cholesterol diet for 1 and 4 weeks, the activity of 24,25-dihydrolanosterol 14
      alpha-demethylase was decreased in the liver. The cytochrome P-45014DM protein
      content detected by immunoblotting was also decreased by cholesterol feeding.
      These results demonstrate that dietary cholesterol acts as a repressive factor
      for lanosterol 14 alpha-demethylase. Further, the activity was enhanced by
      preincubation with phosphatase of the enzyme solution from both the control and
      cholesterol fed rats at the same rate. This result suggests that regulation of
      the activity involves phosphorylation of this enzyme.

PMID- 7581241
TI  - Effect of coumestrol on bone metabolism in organ culture.
AB  - Coumestrol, a representative phytoestrogen, inhibited bone resorption-stimulating
      agent-induced bone resorption, whereas it did not inhibit basal bone resorption
      of cultured fetal rat limb bone. Coumestrol increased the calcium content of 9-d
      old chick embryonic femurs in organ culture, indicating that this phytoestrogen
      stimulated bone-mineralizing activity. Therefore, coumestrol is a unique
      substance in that it inhibits bone resorption and, at the same time, stimulates
      bone mineralization. Coumestrol exhibited less estrogenic activity than 17 beta
      estradiol as estimated by the increase in uterine weight of ovariectomized rats.
      As coumestrol has less estrogenic activity than 17 beta-estradiol, it may prove
      to be a more potent drug against bone diseases including osteoporosis.

PMID- 7581242
TI  - Antihypertensive effect of sesamin. I. Protection against deoxycorticosterone
      acetate-salt-induced hypertension and cardiovascular hypertrophy.
AB  - We investigated the antihypertensive effect of sesamin, a lignan from sesame oil,
      using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The animals were
      unilaterally nephrectomized, and then separated into a sham-operated group (sham
      group) and a DOCA-salt-treated group. The latter was further separated into a
      normal diet group (control group) and a sesamin-containing diet group (sesamin
      group). The systolic blood pressure of control group progressively increased in
      comparison with that of sham group. This DOCA-salt-induced hypertension was
      markedly suppressed by feeding a sesamin-containing diet. Systolic blood pressure
      after 5 weeks was 130.6 +/- 1.9 mmHg in the sham group, 198.1 +/- 7.3 mmHg in the
      control group and 152.5 +/- 8.4 mmHg in the sesamin group, respectively. The
      treatment with DOCA and salt for 5 weeks significantly increased the weight of
      the left ventricle plus the septum. However, this increase was significantly
      suppressed in the sesamin group. When the degree of vascular hypertrophy of the
      aorta and superior mesenteric artery was histochemically evaluated, there were
      significant increases in wall thickness, wall area and the wall-to-lumen ratio in
      the control group, compared with the sham. Sesamin feeding ameliorated the
      development of DOCA-salt-induced vascular hypertrophy in both the aorta and
      mesenteric artery. These findings strongly suggest that sesamin is useful as a
      prophylactic treatment in the development of hypertension and cardiovascular
      hypertrophy.

PMID- 7581243
TI  - Effect of vesicle size on in vivo release of daunorubicin from hydrogenated egg
      phosphatidylcholine-based liposomes into blood circulation.
AB  - The effect of the vesicle size on in vivo release of daunorubicin, an
      anthracycline anticancer drug, from liposomes into the circulation was studied in
      rats. The liposomes were prepared from hydrogenated egg phosphatidylcholine
      (HEPC) or egg phosphatidylcholine (EPC), cholesterol and dicetylphosphate at a
      molar ratio of 5:4:1, and their mean vesicle sizes were adjusted to about 50 and
      100 nm. The drug retained in the liposomes and the drug that leaked were
      separated from plasma by gel filtration. On the assumption that the lipid content
      does not change, the drug release from each liposome preparation was estimated
      from the latency (%) calculated from the drug/lipid concentration ratio of the
      liposome preparation. From HEPC-liposomes with a diameter of 50 nm, the drug was
      released gradually after intravenous administration, and the cumulative percent
      release of the drug reached 40% after 240 min. However, from EPC-liposomes with
      the same size, 50% of the drug was released within 5 min, and more than 90% of
      the drug was released within 60 min. From HEPC-liposomes with a diameter of 100
      nm, no drug release was observed for 240 min after administration. These findings
      indicate that the vesicle size and the lipid composition of liposome preparation
      affect the in vivo drug release.

PMID- 7581244
TI  - Metabolism of irinotecan to SN-38 in a tissue-isolated tumor model.
AB  - The objective of this study is to investigate the metabolism of the antitumor
      drug, irinotecan (CPT-11), to its active metabolite, SN-38, in tumor tissue.
      Using Walker 256 carcinoma, we prepared a tissue-isolated tumor model: tumor
      preparation was continuously perfused with Krebs-Henseleit bicarbonate buffer
      containing 4% bovine serum albumin (BSA) and CPT-11 (10 micrograms/ml), and the
      concentration of SN-38 in the perfusate was monitored using HPLC. The
      concentration of SN-38 in the perfusate was gradually increased to a level of
      9.69 ng/ml 60 min after the start of perfusion. As a control, an aliquot of the
      perfusate was separately incubated; however, no significant increase in SN-38
      levels was observed. At the end of the perfusion, a part of the tumor tissue was
      homogenized and the level of SN-38 was determined; the levels in tumor tissue
      were 2.2-4.5 times higher than in the perfusate. From above results, CPT-11 was
      found to be metabolized to its active metabolite, SN-38, in tumor tissue--a
      desirable feature of an antitumor prodrug.

PMID- 7581245
TI  - Stereoisomeric inversion of (25R)- and (25S)-3 alpha,7 alpha,12 alpha-trihydroxy
      5 beta-cholestanoic acids in rat liver peroxisome.
AB  - The stereoisomeric inversion of (25R)- and (25S)-3 alpha,7 alpha,12 alpha
      trihydroxy-5 beta-cholestanoic acid (THCA) in rat liver peroxisome was studied.
      After incubation of an isomer of THCA-CoA thioester with a peroxisomal fraction,
      5 beta-cholestanoic acids were extracted and optical antipodes were separated and
      determined by LC/APCI-MS. The transformation of (24E)-3alpha,7 alpha,12 alpha
      trihydroxy-5 beta-cholest-24-en-26-oic acid (delta 24-THCA) formed by acyl-CoA
      oxidase was also analyzed by GC/NICI-MS. Rapid enzymatic epimerization from
      either direction was observed prior to biotransformation into (24E)-delta 24
      THCA.

PMID- 7581246
TI  - Screening of polyacetylenic alcohols in crude drugs using the ELISA for
      panaxytriol.
AB  - Polyacetylenic alcohols such as panaxytriol, panaxynol and panaxydol isolated
      from the roots of Panax ginseng C. A. MEYER have antiproliferative activity
      against various cultured tumor cells. Anti-panaxytriol antibody was obtained by
      immunizing rabbits with panaxytriol-bovine serum albumin conjugates. Although the
      antibody reactivity was directed mainly toward panaxytriol, there was a slight
      cross-reactivity with other polyacetylenic compounds. The antibody was,
      therefore, used for screening a large number of crude drugs for polyacetylenic
      compounds such as panaxytriol. Methanol-extracts from 31 crude drugs were
      examined. Significant reactivity was observed in 15 methanol-extracts from
      Aralieaceae, Compositae and Umbelliferae as reported by other investigators.
      Three out of the 15 crude drugs were selected for determination of the potent
      cross-reactive compounds. Four kinds of cross-reactive compounds were isolated by
      silica gel column chromatography, monitoring each fraction using the enzyme
      linked immunosorbent assay (ELISA). Among them, panaxynol and heptadeca-1,8-diene
      4,6-diyne-3,10-diol were identified from Saposhnikoviae Radix. Falcarindiol was
      newly identified from Peucedani Radix. A new polyacetylenic alcohol, 9,10-epoxy
      16-hydroxy-octadeca-17-ene-12,14-diyne-1-al, was also isolated from Foeniculi
      Fructus. All these polyacetylenic alcohols inhibited the growth of a human
      gastric adenocarcinoma cell line, MK-1 cells, in a dose-dependent manner. These
      results indicate that the antibody against panaxytriol is an effective tool for
      "screening" antiproliferative polyacetylenic compounds.

PMID- 7581248
TI  - Inhibitory effect of leupeptin on the intracellular maturation of lysosomal
      cathepsin L in primary cultures of rat hepatocytes.
AB  - To investigate the intracellular processing event for lysosomal cathespin L, we
      examined the effect of leupeptin, a non-covalent cysteine proteinase inhibitor,
      on the intracellular processing kinetics of cathepsin L as analyzed by pulse
      chase experiments in vivo with [35S]methionine in primary cultures of rat
      hepatocytes. This revealed that cathepsin L was initially synthesized as
      proenzyme of molecular weight 39 kDa and the proenzyme was subsequently processed
      to the mature form of the enzyme, 30 and 25 kDa. In the leupeptin-treated cells,
      the proteolytic conversion of cellular procathepsin L, of molecular weight 39
      kDa, to the mature enzyme was significantly inhibited and considerable amounts of
      proenzyme were found in the cell after 8 h chase periods. Furthermore, the
      subcellular fractionation experiment demonstrated that the intracellular
      processing of procathepsin L in the high density lysosomal fraction was
      significantly inhibited and that considerable amounts of the procathepsin L form
      were still observed in the dense lysosomal fraction after a 2 h chase period.
      These results suggest that leupeptin treatment caused significant inhibition of
      the intracellular maturation of cathepsin L. These findings show that cysteine
      proteinase plays an important role in the intracellular proteolytic processing
      and activation of lysosomal cathepsin L in vivo and that this processing event
      occurs within the lysosomes.

PMID- 7581247
TI  - Inhibitory effect of ethanol and colchicine on the intracellular processing of
      beta-glucuronidase which occurs in the Golgi complex.
AB  - To investigate the effect of ethanol or colchicine on the intracellular
      proteolytic processing of lysosomal beta-glucuronidase, which is considered to
      occur in the Golgi complex in the intracellular sorting pathway, three rat liver
      Golgi subfractions, GF-1, GF-2, and GF-3, were isolated from ethanol- or
      colchicine-treated rats, and the electrophoretic patterns of the extracted Golgi
      beta-glucuronidase on polyacrylamide gel were examined. The isolated Golgi
      subfractions from the drug-treated rats gave a better yield of fraction than that
      from the control rats. The enzymatic characterization of these three subfractions
      showed no significant contamination by other subcellular structures such as
      plasma membranes, microsomes, or lysosomes, and no inhibitory effect of the drugs
      was observed. On the other hand, suppressed galactosyltransferase activity, a
      marker enzyme of the Golgi complex, was detected in the colchicine-treated rats.
      The electrophoretic pattern of Golgi beta-glucuronidase on polyacrylamide gel
      revealed one major band which moved to the same position as the lysosomal enzyme
      type in the control rats. In contrast, in the ethanol- and colchicine-treated
      rats, Golgi beta-glucuronidase was found to have two major bands stained for
      enzyme activity resulting from a mixture of microsomal- and lysosomal-type
      enzymes. These results suggested that the post-translational modification step,
      during conversion from a microsomal-type enzyme to a lysosomal-type enzyme, was
      apparently inhibited. Taken together, these findings indicated that ethanol or
      colchicine administration to rats caused an inhibitory effect on the
      intracellular post-translational modification of Golgi beta-glucuronidase
      destined for targeting to the lysosomes.

PMID- 7581249
TI  - Differential effects of selective beta 1-agonist stimulation on epi- and
      endocardial oxygen tension in anesthetized dogs.
AB  - We investigated the effects of selective beta 1 adrenoceptor stimulation on
      oxygen tension (pO2) in the myocardium of anesthetized dogs. A beta 1-selective
      full agonist, T-0509 (0.01-0.05 microgram/kg, i.v.), caused positive inotropic
      and chronotropic effects, and increased left circumflex blood flow, although it
      did not change arterial blood pressure. These effects were inhibited by
      bisoprolol (10 micrograms/kg), but not by ICI 118551 (30 micrograms/kg). Under
      control conditions, subepicardial pO2 (pO2 epi) and subendocardial pO2 (pO2endo)
      were approximately 33 and 27 mmHg, respectively. T-0509 (0.05 microgram/kg)
      decreased pO2epi in all cases, with a mean decrease of 2.6 +/- 0.5 mmHg, and this
      was significantly inhibited by bisoprolol. T-0509 caused an increase (7 out of 10
      dogs) or a slight decrease (3 out of 10) in the pO2endo; the mean increment was
      2.0 +/- 1.3 mmHg (n = 10). Isoproterenol (0.01-0.05 microgram/kg, i.v.) exerted
      positive inotropic and chronotropic effects that were sensitive to bisoprolol,
      and a hypotensive effect that was sensitive to ICI 118551. Isoproterenol caused
      an increase in blood flow that was sensitive to ICI 118551. Isoproterenol (0.05
      microgram/kg) decreased pO2epi in all cases, with a mean decrease of 2.7 +/- 0.5
      mmHg, which was significantly inhibited by bisoprolol. Isoproterenol caused an
      increase (5 out of 10) or a slight decrease (5 out of 10) in the pO2endo; the
      mean increment was 1.1 +/- 1.2 mmHg (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581250
TI  - Relationship between age and nephrotoxicity following single low-dose cisplatin
      (CDDP) injection in rats.
AB  - We studied nephrotoxicity following a single injection of cisplatin (CDDP) at low
      dose (1 mg/kg) in two groups of rats aged 52 weeks (adult, A group) and 9 weeks
      (young, Y group). Renal platinum (Pt) was detectable in both groups 3 h after the
      CDDP injection, and, from 6 h to 3 d after injection, its level in the A group
      was higher than that in the Y group. Compared with the levels in age-matched
      normal rats (non-treated rats examined at time zero), the plasma urea nitrogen
      and creatinine levels in the A group were significantly increased, beginning 3 d
      after CDDP injection, while those in the Y group showed little change for 10 d
      after injection. Beginning 3 d after CDDP injection, the level of renal
      metallothionein in the Y group increased, while that in the A group decreased
      remarkably. The renal tissue levels of the heavy metals Zn, Cu, Mn showed similar
      patterns. There were no significant changes in the renal lipid peroxide (LPO)
      level in either the A and Y group at any time measured after CDDP injection
      compared with the value in the respective age-matched untreated group.
      Morphological evaluation demonstrated degeneration of the proximal tubules in the
      A group 3 d after CDDP injection. These results suggested that the renal
      disorders observed following CDDP injection in the A group were caused by
      mechanisms other than LPO such as decreased tissue metabolic function associated
      with aging.

PMID- 7581251
TI  - Inhibitory effects of methanolic extract from corydalis tuber against types I-IV
      allergic models.
AB  - Methanolic extract (CM-ext) from tubers of Corydalis turtschaninovii forma
      yanhusuo has been screened for activity in experimental models of types I-IV
      allergy. In type I allergic models, CM-ext at doses of 200, 500 mg/kg, p.o.
      inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in rats which is
      related to IgE, and 4-h heterologous PCA in guinea pigs which is related to IgG.
      The inhibition of CM-ext on 48-h PCA was also recognized in adrenalectomized
      rats. CM-ext exhibited the inhibitory effect on formation of IgE antibody in
      BALB/c mice. In type II allergic model, it was found that CM-ext inhibits
      reversed cutaneous anaphylaxis (RCA). In type III allergic model, CM-ext showed
      the inhibitory effect on direct passive arthus reaction (DPAR) in rats.
      Furthermore, in type IV allergic model, CM-ext had the inhibitory effects on
      induction phase and effector phase in picryl chloride-induced contact dermatitis
      (PC-CD). It also showed therapeutic action on PC-CD. These results indicated that
      CM-ext not only inhibits antibody-mediated allergic reactions but also influences
      cell-mediated allergic reactions and should be recognized as a potent material
      for allergic reactions, although the mechanisms and active principles of CM-ext
      have not yet been completely determined.

PMID- 7581253
TI  - Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH)
      analogue. II. In situ and in vitro absorption characteristics of azetirelin from
      the rat intestine.
AB  - Intestinal absorption characteristics of azetirelin, a new thyrotropin-releasing
      hormone (TRH) analogue, were studied in rats by means of in situ closed loop and
      in vitro everted sac experiments. Plasma concentrations of azetirelin obtained in
      the in situ closed loop experiments were not significantly different among the
      intestinal segments. Area under the plasma concentration-time curve (AUC) of
      azetirelin following administration into the duodenal loop increased in
      proportion to the dose. The serosal to mucosal concentration ratio of the
      analogue in the everted sac experiment was constant over the mucosal drug
      concentration range of 0.01-10 mM. There was no directional difference in the
      transfer rate of azetirelin across the everted and non-everted sacs of the
      duodenum. Furthermore, its transport across the duodenum was not influenced by
      low incubation temperature (25 degrees C), addition of dipeptide (Gly-Gly), or
      pretreatment of the mucosal surface with 2,4-dinitrophenol, while that of TRH was
      inhibited under these conditions. These results suggest that the intestinal
      absorption mechanism of azetirelin is different from that of TRH, and that
      azetirelin is predominantly transported via a passive diffusion.

PMID- 7581254
TI  - Effect of temperature in perfusate on local hepatic disposition of BOF-4272, a
      new xanthine oxidase inhibitor.
AB  - The effect of temperature on the local hepatic disposition of BOF-4272 [(+/-)-8
      (3-methoxy-4-phenylsulfinyl-phenyl)pyrazolo[1,5-a]-1,3,5- triazine-4-olate], a
      new drug used to treat hyperuricemia, was investigated by means of a perfusion
      experiment following the pulse input into the portal vein of rat, in which the
      temperature of the perfusate was changed from 37 degrees C down to 4 degrees C.
      The same perfusion experiment was also attempted using bovine serum albumin (BSA)
      as a reference substance to compare with the hepatic disposition of BOF-4272. The
      elution time profiles of BOF-4272 and BSA from the liver into the hepatic vein
      were evaluated by moment analysis. The recovery ratio (FH) and the mean transit
      time (tH) of BOF-4272 were 22.8 +/- 3.3% and 0.111 +/- 0.008 min at 37 degrees C,
      respectively. Both FH and tH significantly increased with the decrease in the
      temperature of the perfusate, 3 times and 2 times greater at 4 degrees C than at
      37 degrees C, respectively. The FH and tH of BSA were 98.3 +/- 4.5% and 0.129 +/-
      0.013 min at 37 degrees C, respectively. These parameters of BSA were independent
      of temperature, while those of BOF-4272 showed a definite dependency on
      temperature. A new estimation method for the elimination rate constant (kc) and
      the partition ratio (k') in the dispersion model was developed by rearranging the
      theoretical equations of FH and tH. The index for the elimination (ke) of BOF
      4272 decreased with the decrease in temperature, while the index for the
      distribution (k') increased with the decrease in temperature. This result shows
      that the metabolism (or the biliary excretion) decreased and the distribution
      increased with a decrease in temperature, indicating that the hepatic
      metabolizing pathway which is presumably temperature-dependent is blocked, and
      the blocked portion of BOF-4272 thus returns back to the perfusate at the low
      temperature.

PMID- 7581252
TI  - Comparison of the in vitro skin penetration of propiverine with that of
      terodiline.
AB  - This study was designed to clarify the relationship between the properties of
      propiverine and skin penetration, and to compare the in vitro penetration
      characteristics of propiverine and terodiline through rat skin. Propiverine in
      both hydrochloride and free forms penetrated across the skin extremely slowly,
      with a 2.6 times higher flux in the hydrochloride than that in the free base, in
      the absence of enhancers. Various enhancers failed to enhance the penetration of
      propiverine hydrochloride, whereas the same agents slightly increased the flux of
      the free form, these being due to the slow release rate of the free form from the
      gel formulations, an extremely high lipophilicity (log Poct/water > 4.97), much
      less solubility (0.141 mg/ml) and a large partition capacity of the drug to skin
      components. Terodiline in both forms was able to rapidly penetrate through the
      skin, even in the absence of enhancers, with 20.2 and 9.8 times higher fluxes
      respectively, than the corresponding forms of propiverine. The high penetration
      characteristics of terodiline would be due to a suitable lipophilicity, low
      binding property as well as the structural masking from the binding to the
      epidermal components. Propiverine hydrochloride penetrated through the stratum
      corneum 4.4 times and viable skin 3.1 times higher than through full-thickness
      skin, while the fluxes of terodiline through the stratum corneum and viable skin
      were similar to each other, with high penetration rates for each form.

PMID- 7581255
TI  - Preparation of controlled release tablets of TA-5707F with wax matrix type and
      their in vivo evaluation in beagle dogs.
AB  - Studies on controlled release dosage forms were conducted by using waxy materials
      for a newly developed anti-allergy drug, 6-methyl-N-(1H-tetrazol-5-yl)-2
      pyridinecarboxamide (TA-5707F), which is not maintained at an effective level in
      blood for a long duration. Four kinds of tablets were prepared by changing the
      amount of hydrogenated oil (K3 wax) and polyethyleneglycol-6000 in the tablets.
      Then, they were administered orally to beagle dogs, and the TA-5707F
      concentration in the plasma was determined by a HPLC method. The pharmacokinetic
      parameters were estimated and compared with the results of the in vitro
      dissolution test determined by the JP paddle method and by the disintegration
      method. The linearity between the in vivo mean dissolution time (MDT) and in
      vitro MDT was good in both in vitro dissolution methods. However, the MDTs
      obtained by the disintegration method were one-third of the in vivo MDT, while
      those obtained by the paddle methods were 3 times higher. This suggests that both
      the diffusion of TA-5707F through the waxy matrix and the erosion of the wax
      matrix caused by the gastrointestinal (GI) tract mobility contributed to the in
      vivo dissolution mechanism. The blood levels were very low when the tablet was
      administered after giving food. The prolongation of resident time in the stomach
      and the low solubility of TA-5707F in an acidic medium seemed to be related to
      the phenomena. By the depression of GI motility using propantheline bromide, the
      blood levels could be markedly prolonged and the area under the plasma
      concentration-time curve (AUC) increased 1.3 times.

PMID- 7581256
TI  - Pharmacokinetic and pharmacodynamic studies of chlorpromazine in rats: effect of
      chlorpromazine on dopamine and dopamine metabolite concentration in rat striatum.
AB  - The concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) in rat striatum were increased after the i.v.
      administration of chlorpromazine (CPZ). Assuming that the enhancement of dopamine
      concentration in the striatum after CPZ administration is caused by the release
      of dopamine from the dopamine neuronal terminals, the relationship between the
      enhancement of dopamine concentration in the striatum and CPZ concentration in
      the cerebrospinal fluid (CSF) and the striatum were analyzed using the sigmoid
      Emax model. The enhancement of dopamine concentration in the striatum could be
      described quantitatively by this model. The time courses of DOPAC and HVA
      concentration in the striatum after CPZ administration were analyzed using the
      dopamine metabolism model, which has an apparent first-order clearance from
      dopamine to DOPAC and HVA, and also using the Michaelis-Menten type elimination
      kinetics of DOPAC and HVA. The values of the metabolism parameters for DOPAC and
      HVA were fixed to the estimated values of the L-dopa study. The calculated values
      of DOPAC and HVA concentrations in the striatum were greater than those of the
      observed data. The elimination parameters for DOPAC and HVA were reestimated by
      the nonlinear least squares method. The time courses of DOPAC and HVA
      concentration in the striatum could be described using these reestimated
      elimination parameters. These results indicated that the turnover rate of
      dopamine and dopamine metabolites, DOPAC and HVA in the striatum after CPZ
      administration is different from that after L-dopa administration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581257
TI  - Structure-activity correlationship and strain specificity of polyoxometalates in
      anti-human immunodeficiency virus activity.
AB  - The anti-human immunodeficiency virus (HIV) activity of polyoxometalates of
      representative structural families, such as Keggin, lacunary Keggin, trivacant
      Keggin, Keggin sandwich, Wells-Dawson and Wells-Dawson sandwich, was determined
      using two strains of HIV type 1 (HIV-1HTLV-IIIB and HIV-1SF-2H). The compounds
      were preferably selected to cover both polyoxotungstates and polyoxomolybdates in
      each structural family. In general, polyoxotungstates of Keggin, lacunary Keggin,
      trivacant Keggin, Keggin sandwich, Wells-Dawson and Wells-Dawson sandwich
      structures showed anti-HIV-1HTLVIIIB activity, whereas most compounds not
      included in these structural categories were inactive. Among the compounds with a
      potent anti-HIV-1HTLV-IIIB activity, those of Keggin and its closely related
      structural families (lacunary Keggin, trivacant Keggin and Keggin sandwich)
      inhibited the cytopathogenicity and syncytium formation caused by HIV-1SF-2 to a
      much higher extent compared with HIV-1HTLV-IIIB-related ones. The difference
      between the spectra of anti-HIV-1HTLV-IIIB activity and the specificity for HIV
      1SF-2H might result from differential structural requirements in these functions.

PMID- 7581258
TI  - Interaction of a neutral endopeptidase inhibitor with an ANP-C receptor ligand in
      anesthetized dogs.
AB  - Inhibition of important degradative pathways of atrial natriuretic peptide (ANP)
      in vivo could be a valuable therapeutic tool for regulating endogenous levels of
      ANP. The aim was to investigate the in vivo effects of both blockade of atrial
      natriuretic peptide clearance receptor and inhibition of neutral endopeptidase
      24.11, an enzyme shown to be involved in ANP breakdown. Therefore, we infused a
      specific neutral endopeptidase inhibitor ((S)-thiorphan) and an ANP-C receptor
      ligand (AP 811) alone or in combination into anaesthetized beagle dogs. Compared
      with vehicle controls, coadministration of (S)-thiorphan and AP 811 (100
      micrograms/kg/min and 10 micrograms/kg/min, resp.) had greater effects on
      endocrine and renal parameters than administration of either substance alone.
      Coadministration of both compounds increased urinary excretion of volume and
      sodium, cGMP and ANP. We found also increased plasma cGMP, plasma ANP and
      decreased plasma renin activity. No effects were observed with respect to blood
      pressure, left ventricular pressure or heart rate during the infusion period of 2
      h. We conclude from these investigations, that blocking both degrading pathways
      of ANP with the ANP-C receptor ligand AP 811 and the neutral endopeptidase
      inhibitor (S)-thiorphan is more effective than inhibition of either system alone.
      Such a combination might therefore be a useful therapeutic tool in cardiovascular
      diseases.

PMID- 7581259
TI  - Angiotensin II induces the expression of c-fos mRNA in the central nervous system
      of the rat.
AB  - We have investigated the effects of intracerebroventricular injections of
      angiotensin II in conscious rats on the expression of c-fos messenger RNA (mRNA)
      in the caudate nucleus, hypothalamus, midbrain and brainstem using semi
      quantitative polymerase chain reaction and Northern Blots. RNA analysis revealed
      the presence of c-fos transcripts in the midbrain and brainstem following icv
      injections of ANG II. ANG II (1, 10, 100 ng) induced a substantial increase in c
      fos mRNA in the brainstem which was significant after 10 ng ANG II, and less
      after 100 ng. This effect was time-dependent being detectable within 15 minutes
      and maximal after 60 minutes. This ANG II-induced c-fos mRNA expression was
      totally inhibited by icv pretreatment with the ANG II-AT1 receptor antagonist,
      losartan. Our data show for the first time that stimulation of central
      periventricular AT1 receptors induces the expression of c-fos mRNA in the brain.
      Thus, ANG II, in addition to its short-term regulatory actions, can participate
      through transcription factors in neuroplastic processes.

PMID- 7581260
TI  - Localization of calcium channels of the L-type in human epicardial arteries: a
      light microscope autoradiographic study.
AB  - The anatomical localization of Ca2+ channels of the L-type was analyzed in
      sections of the human right and anterior interventricular coronary arteries by
      using in vitro light microscope autoradiography associated with radioligand
      binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the
      radioligand to sections of the two coronary arteries was time-, temperature- and
      concentration-dependent. Analysis of binding isotherms revealed a dissociation
      constant value of about 0.5 nM in the two arteries and maximum binding capacities
      of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5
      for the anterior interventricular branch. The pharmacological profile of
      [3H]nicardipine binding to sections of human coronary arteries was consistent
      with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives
      were the most powerful competitors of [3H]nicardipine binding, whereas
      phenylalkylamines, benzothiazepine or non-selective channel modulators were weak
      competitors or ineffective. Light microscope autoradiography revealed the highest
      density of [3H]nicardipine binding sites in the tunica media of the coronary
      arteries. In this layer Ca2+ channels of the L-type are located within smooth
      muscle cells. A lower accumulation of the radioligand occurred in the tunica
      adventitia, whereas no specific binding was found in the tunica intima. Study of
      the localization of Ca2+ channels in sections of human coronary arteries may
      contribute to a better understanding of the mechanism of the marked coronary
      dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro
      preparations and in vivo.

PMID- 7581262
TI  - In vivo pharmacology of L-159,913, a new highly potent and selective nonpeptide
      angiotensin II receptor antagonist.
AB  - The present study was designed to characterize the in vivo pharmacology of L
      159,913 (4-[[2'-(N-benzoylsulfamoyl)biphenyl-4-yl]-5butyl-2,4-dihydr o-2- [2
      (trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one); a potent All receptor
      antagonist. In normotensive rats, dogs, rhesus monkeys, and chimpanzees, L
      159,913 inhibited All-induced elevations in blood pressure. In conscious rats,
      the relative potencies (ED50) were 0.51 mg/kg i.v. and 0.72 mg/kg p.o. Duration
      of action with single i.v. or p.o. doses exceeded 6 hr in rats. L-159,913 was 3
      times less potent than losartan in rats and equipotent to losartan in monkeys.
      All induced elevation of plasma aldosterone in rats was also inhibited by L
      159,913. L-159,913 was antihypertensive in high renin hypertensive rats (aortic
      coarctation). The maximum hypotensive response to an acute dose of L-159,913 (10
      mg/kg, po) was equal to that of enalaprilat (0.3 mg/kg, iv) in this renin
      dependent animal model. In conscious normotensive dogs, L-159,913 had a moderate
      diuretic, natriuretic and kaliuretic response with no effect on glomerular
      filtration rate, effective renal plasma flow or filtration fraction, suggesting a
      tubular site of action. L-159,913 is a selective and potent All receptor
      antagonist with good oral activity, long duration of action and antihypertensive
      efficacy.

PMID- 7581263
TI  - Alpha 2-adrenoceptors in brain and kidney during development of hypertension in
      Dahl-Iwai salt-sensitive rats.
AB  - BACKGROUND: Both renal and extrarenal factors have been considered to contribute
      to the development of hypertension in Dahl salt-sensitive rats, but contents of
      both factors have not been established precisely. AIM: To clarify the role of
      those factors in the sympathetic nervous system, we examined the regulation of
      alpha2-adrenoceptors in the lower brainstem and the renal tubular basolateral
      membranes simultaneously during the development of salt-induced hypertension in
      Dahl-Iwai salt-sensitive rats. METHODS: Dahl-Iwai salt-sensitive or resistant
      rats were fed a high (8.0% NaCl)- or low (0.3%)- salt diet from 4 to 6 or 10
      weeks of age. At 4, 6 and 10 weeks of age, the plasma membranes of the lower
      brainstem and the renal tubular basolateral membranes were obtained
      simultaneously and alpha 2-adrenoceptors were quantified by a radioligand binding
      assay using 3H-rauwolscine. RESULTS: In the salt-sensitive rats, systolic blood
      pressure was significantly higher in those fed a high-salt diet than in those fed
      a low-salt diet. In the salt-resistant rats, both the high- and the low-salt
      groups showed similar blood pressure levels. At 6 weeks of age, alpha 2-receptor
      densities of the salt-sensitive rats fed a high-salt diet were lower in the lower
      brainstem and higher in the renal basolateral membranes than those fed a low-salt
      diet. In contrast, in the salt-resistant rats, both the high- and the low-salt
      groups had similar densities. At 10 weeks of age, the difference between the high
      and the low-salt groups in the salt-sensitive rats disappeared in both the
      brainstem and the renal basolateral membranes. CONCLUSIONS: Alpha 2-adrenoceptor
      regulation in the brainstem and the renal basolateral membranes differs between
      Dahl-Iwai salt-sensitive and salt-resistant rats. The modulation of alpha 2
      adrenoceptors by a high salt intake may be essential particularly in the early
      phase of the development of salt-induced hypertension.

PMID- 7581265
TI  - Potassium depletion and salt-sensitive hypertension in Dahl rats: effect on
      calcium, magnesium, and phosphate excretions.
AB  - Weanling male inbred Dahl rats (Jr salt-sensitive (S) and salt-resistant (R)
      strains) were placed on high (4%, HK) and low (0.2%, LK) potassium diets for 4
      weeks. Both diets contained 8% sodium chloride, 2.5% calcium, 0.8% magnesium, and
      2.0% phosphorous. Balance studies were carried out during the final week on the
      diets. Mean arterial blood pressure was determined, and dietary intake and
      urinary output of water, sodium, chloride, potassium, calcium, magnesium, and
      phosphate were monitored daily during this period. The data show that blood
      pressures of S rats were significantly higher than those of R rats on both HK and
      LK diets; however, reduced dietary potassium was associated with increased blood
      pressure in both strains. Urinary excretions of calcium and magnesium were
      higher, and urinary phosphate excretion was lower, in S compared to R rats.
      Decreased potassium intake was associated with increased excretion of calcium,
      magnesium and phosphate in both strains. The changes in calcium and magnesium
      excretion were significantly correlated to blood pressure across strains and
      diets. We conclude that the effects of a high salt diet on increasing blood
      pressure can be potentiated by lack of potassium, even in previously salt
      resistant rats. Increased blood pressure is associated with increased divalent
      cation excretion. It is not yet known whether this is a cause-and-effect
      relationship.

PMID- 7581261
TI  - Metformin attenuates agonist-stimulated calcium transients in vascular smooth
      muscle cells.
AB  - Metformin, an antidiabetic agent that increases insulin sensitivity, has been
      shown to lower blood pressure. However, the mechanism of action of metformin in
      vascular smooth muscle (VSM) cell is not fully understood. We have tested the
      hypothesis that metformin produces vascular changes by direct interaction with
      VSM cells by investigating its effect on platelet-derived growth factor (PDGF)-
      and angiotensin II (ANG II)-stimulated intracellular calcium concentration
      ([Ca2+]i) and VSM cell proliferation in response to PDGF in cultured cells. VSM
      cells were cultured from rat thoracic aorta and [Ca2+]i was estimated in single
      cells by image analysis. Treatment of VSM cells with 1 or 2 microgram/ml
      metformin significantly decreased (p < 0.05) PDGF- or ANG II-stimulated [Ca2+]i.
      Treatment of VSM cells with 1, 2, 5, or 10 micrograms/ml metformin had no
      significant effect on PDGF-stimulated [3H]-thymidine incorporation. However,
      metformin at pharmacological doses of 20 and 50 micrograms/ml significantly
      reduced (p < 0.05) PDGF-stimulated thymidine incorporation. We conclude that
      metformin mediates its vascular effects by attenuating agonist-stimulated
      [Ca2+]i.

PMID- 7581266
TI  - Nitric oxide-dependent killing of Candida albicans by murine peritoneal cells
      during an experimental infection.
AB  - The phagocytic and candidacidal activities of the peritoneal cells of Candida
      albicans-infected mice were studied 20 days following experimental infection.
      Both activities were enhanced during infection. The production of nitric oxide
      (NO) by the peritoneal cells of infected mice was determined, and an increase in
      the nitrite concentration in supernatants of peritoneal cell cultures was
      detected. The period of NO production by the peritoneal cells coincided partially
      with the period of enhanced C. albicans killing. The inhibition of NO synthesis
      by N-monomethyl-L-arginine was concomitant with inhibition of candidacidal
      activity. We conclude that NO synthesis is the primary candidacidal mechanism of
      the murine peritoneal cells activated by C. albicans infection.

PMID- 7581268
TI  - Prophylactic use of human endotoxin-core hyperimmune gammaglobulin to prevent
      endotoxaemia in colostrum-deprived, gnotobiotic lambs challenged orally with
      Escherichia coli.
AB  - The efficacy of human IgG polyclonal antibody to endotoxin-core in preventing
      endotoxaemia and subsequent disease was studied in colostrum-deprived gnotobiotic
      lambs challenged orally at about 5 h old with 10(9) cfu Escherichia coli. Human
      endotoxin-core hyperimmune gammaglobulin was given intravenously to 5 lambs at
      1.9 g IgG/kg bodyweight prior to challenge. Human albumin was given intravenously
      to 3 control lambs. Bacteraemia was observed in all lambs, but the incidence was
      lower (P < 0.01) and the onset later (P < 0.05) in gammaglobulin pre-treated
      lambs. These lambs showed no signs of disease, whereas clinical endotoxaemia,
      manifesting as watery mouth disease, was diagnosed in 2 of the 3 control lambs
      which were killed between 18 and 22 h after challenge. Thus, prophylactic
      treatment of colostrum-deprived lambs with human IgG enriched in endotoxin-core
      antibodies was effective in reducing the degree of bacteraemia and preventing
      endotoxaemia, leukopenia and clinical disease following oral challenge with E.
      coli.

PMID- 7581267
TI  - Immunoaffinity chromatographic isolation of a high molecular weight seroreactive
      protein from Mycobacterium leprae cell sonicate.
AB  - The purpose of this study was to isolate Mycobacterium leprae antigen(s) by
      immunoaffinity chromatography using immunoglobulins from leprosy patients and
      from rabbit anti-M. leprae hyperimmune serum coupled to CNBr-Sepharose 4B. A high
      molecular weight (M(r)) M. leprae protein (MLP) with a subunit M(r) of 22,000 was
      isolated. MLP was recognized by monoclonal antibody MMPII1G4 which is known to
      react with MMPII, a 22 kDa protein of M. leprae. The N-terminal sequence of the
      22 kDa subunit (Met-gln-gly-asp-pro-asp-val-leu-arg-leu-leu-asn-glu-gln-leu-thr)
      was identical to MMPII and to antigen D (bacterioferritin) of M.
      paratuberculosis. It showed 44% homology with N-terminal end of E. coli
      bacterioferritin. In ELISA, MLP showed 100% and 60% positivity with leprosy and
      TB sera respectively as compared to normal healthy sera. The role of
      bacterioferritin in M. leprae and the importance of MLP as an immunogen has been
      discussed.

PMID- 7581264
TI  - Hypertensive response to acute aortic coarctation in chronic vasopressin
      deficient states.
AB  - We investigated the genesis of the hypertensive response to acute (45 min) aortic
      constriction in two models of chronic vasopressin (AVP) deficiency, i.e.,
      Brattleboro strain and median eminence lesioned (MEL) Wistar rats. The same
      degree of partial aortic constriction, with a pneumatic cuff placed around the
      abdominal aorta, yielded a sudden and maintained increase in carotid pressure to
      the same extent in Brattleboro, MEL and sham-MEL rats. Blockage of AVP V1
      receptors with d(CH2)5Tyr[Me]AVP did not affect the hypertensive response of
      Brattleboro or MEL rats, but gradually blunted the response of sham-MEL rats.
      Blockage of angiotensin II receptors with saralasin blunted the hypertensive
      response of the AVP-deficient subjects throughout the experiment, but only
      delayed (5-15 min) the onset of hypertension in sham-MEL rats. Simultaneous
      blockage of AVP and angiotensin II blunted the hypertensive response of sham-MEL
      and AVP-deficient rats throughout the experiment. These data demonstrate that
      when one vasoactive system is chronically absent, as is the case for AVP in
      Brattleboro and MEL rats, the renin-angiotensin system plays the major role in
      the pathophysiology of acute aortic coarctation hypertension.

PMID- 7581269
TI  - Pathogenesis of Rhodococcus equi infection in mice: roles of virulence plasmids
      and granulomagenic activity of bacteria.
AB  - Virulence of Rhocococcus equi ATCC 33701 and its plasmid-cured derivative ATCC
      33701P- was compared in BALB/c and C3H/HeJ mice in terms of bacterial growth
      kinetics and histological changes in the liver, spleen and lungs, and humoral
      immune responses. Injection with a sublethal dose of 10(6) ATCC 33701 in mice
      resulted in microabscess formation after rapid multiplication in the liver and
      spleen by day 4, and then the bacteria were gradually eliminated with the
      formation of granuloma and the production of specific antibodies against 15- to
      17-kDa antigens of the virulent bacteria. By contrast, ATCC 33701P- was avirulent
      as shown by early elimination of viable bacteria and no evidence of net
      multiplication in the organs. Histopathological changes consisted of only slight,
      transient infiltration of neutrophils and macrophages in the liver. Although live
      ATCC 33701P- did not evoke any humoral or histological responses in the mice, a
      large inoculum (10(8)) of killed ATCC 33701 and ATCC 33701P- resulted in the
      formation of granuloma in the liver and accelerated extramedullary hemopoiesis in
      the spleen. These results suggest that the pathogenesis of R. equi infection
      involves at least two important virulence determinants, both of which play
      critical roles in the disease: one is the virulence plasmid, which is required
      for R. equi to resist and grow within host cells; and the other is the
      granulomagenic activity that is related to the lipids and nature of the cell wall
      of the species, which induces the characteristic pathological changes.

PMID- 7581270
TI  - Purified Pseudomonas aeruginosa PA-I lectin induces gut growth when orally
      ingested by rats.
AB  - The effects of PA-I lectin isolated from the human pathogen Pseudomonas
      aeruginosa upon cellular metabolism in vivo have been studied using the rat gut
      as a model system. Orally ingested PA-I lectin stimulated metabolic activity and
      induced polyamine accumulation and growth in the small intestine, caecum and
      colon. The nature and extent of the changes induced by PA-I lectin were similar
      to those caused by dietary kidney bean lectin and were likely to lead to impaired
      epithelial cell function and integrity. This finding contributes to our
      understanding of the possible roles of these lectins in Pseudomonas aeruginosa
      infection.

PMID- 7581271
TI  - A peptide, ALTTE, within the fimbrial subunit protein from Porphyromonas
      gingivalis, induces production of interleukin 6, gene expression and protein
      phosphorylation in human peripheral blood mononuclear cells.
AB  - Porphyromonas gingivalis 381 fimbriae and a synthetic peptide composed of
      residues 69-73 (ALTTE) of the fimbrial subunit protein, FP381(69-73), function in
      the induction of interleukin 6 (IL-6) production, IL-6 mRNA expression, and
      tyrosine and serine/threonine phosphorylation of several proteins in human
      peripheral blood mononuclear cells (PBMC). Herbimycin A and H-7, inhibitors of
      tyrosine kinases and protein kinase C (PKC), markedly inhibited IL-6 production,
      gene expression, and tyrosine and serine/threonine phosphorylation of proteins.
      An inactive analog of synthetic peptide replaced alanine to glycine at position
      69 in FP381(69-73), GLTTE, exhibited an antagonistic effect on the IL-6
      production induced by the fimbriae. These results suggest that the peptide ALTTE
      functions as an agent in inflammatory reactions and immune responses in the
      inflamed gingival and periodontal tissues, in which the participation of protein
      phosphorylation by tyrosine kinases and PKC in signal transduction may be
      considered.

PMID- 7581272
TI  - Complement resistance is a virulence factor of Branhamella (Moraxella)
      catarrhalis.
AB  - The purpose of this study was to investigate complement resistance in Branhamella
      (Moraxella) catarrhalis isolated from healthy schoolchildren or sputum-producing
      adult patients. Two techniques were used: a serum bactericidal assay as the gold
      standard and an easier 'culture and spot' test. Children (age 4-13; n = 303) and
      patients (n = 1047) showed high colonization/infection rates with B. catarrhalis
      (31% and 19%, respectively). Complement resistance or intermediate sensitivity
      occurred frequently in patient isolates (62% and 27%, respectively) and less
      often in children (33% and 8.5%, respectively; P << 0.0001). In young children
      (age 4-5 years), the proportion of complement-resistant strains was around 50%.
      Complement resistance in B. catarrhalis is associated with illness and may hence
      be considered a virulence factor.

PMID- 7581275
TI  - Modification of delayed-type hypersensitivity reactions by muramyldipeptide in
      guinea pigs.
AB  - N-Acetylmuramyl-L-alanyl-D-isoglutamine (muramyldipeptide, MDP) modulated delayed
      type hypersensitivity (DTH) reactions and induced severe inflammatory lesions in
      guinea pigs. The animals immunized with heat-killed Mycobacterium tuberculosis
      were challenged with the purified protein derivative (PPD) at the flanks and the
      corneas to prepare DTH reactions at 2 weeks after the immunization, thereafter 24
      h the animals received subcutaneous injections of MDP at the flanks of the
      opposite side. At the skin with the DTH reaction, increase of swelling and
      redness accompanied with hemorrhage and necrosis were observed. As corneal
      reactions in the animals that had received MDP, increase of cornea thickness,
      opaque and grayish-white and the projection of eyes accompanied with severe
      iritis were observed. Modification of the skin reaction occurred from 2 h after
      the MDP injection, rapidly increased to the maximum level around 10 h, maintained
      the level until 24 h, then slowly decreased. The polymorphonuclear leukocyte
      infiltration was observed from 15 min after the MDP injection, and tumour
      necrosis factor alpha, interleukin (IL)-1, and IL-6 levels in the serum and skin
      lesions increased after the MDP injection. Synthetic muramyltripeptide (N
      acetylmuramyl-L-alanyl-D-isoglutaminyl-L-lysine) also provoked definite skin
      reactions, while the larger peptidoglycan fragments and various inflammatory
      agents including cytokines so far examined were inactive in this respect.
      Cortisone and heparin inhibited definitely and slightly the reaction,
      respectively. A comparison was made with the modified DTH reaction and the
      necrotic reactions which we reported previously.

PMID- 7581273
TI  - Influence of staphylococcal enterotoxin B (SEB) on the course of murine
      listeriosis.
AB  - Confrontation of the immune system with bacterial superantigens leads to an
      initial activation of the immune system followed by a state of profound
      immunosuppression. To investigate the role of a superantigen in an acute
      infection with a facultatively intracellular bacterium, we have studied the
      effect of staphylococcal enterotoxin B on the course of murine listeriosis.
      Intraperitoneal injection of SEB led to a statistically significant growth
      restriction of Listeria monocytogenes in the organs of mice infected
      intravenously or intraperitoneally when treatment with SEB and infection with L.
      monocytogenes were given simultaneously or when the mice were treated two days
      before infection. No effect of SEB on murine listeriosis was found when SEB was
      given more than two days before infection or one or more days after infection. We
      conclude that initial immunostimulation by SEB which is indicated by a massive
      liberation of all interleukins measured (IL1 alpha, IL6, TNF alpha, IL2, IFN
      gamma, IL4) is responsible for the growth restriction of L. monocytogenes in the
      organs of treated mice. Apoptosis of V beta 8 positive T cells which was
      accompanied by a 30% reduction of these cells at day 7 after treatment seems to
      be totally compensated.

PMID- 7581274
TI  - Development and characterization of monoclonal antibodies specific for the genus
      Listeria.
AB  - Monoclonal antibodies were obtained by the classic hybridoma technique with
      lymphocytes of BALB/c mice immunized with formalin killed Listeria monocytogenes
      cells. Among 1000 hybridomas issued from the fusion, four monoclonal antibodies
      (mAbs A6 A E4, C10 A F7, G4 A D6, G7 A D5) gave interesting results. By Western
      blot analysis with various soluble extracts of different Listeria species, the
      four mAbs reacted with two major antigens of 38 and 41 kDa, with all Listeria
      species tested. The mAb A6 A E4 is an IgG2b with kappa light chains and reacted
      only with Listeria antigens without any cross reaction with other organisms
      tested by ELISA, dot-blotting and Western-blotting. With the same conditions, the
      three other mAbs reacted with Listeria and with other genus extracts,
      particularly with Streptococcus and Enterococcus. mAb A6 A E4-reactive antigens
      are proteins, and glycoprotein immunoassay indicated that the epitope is devoid
      of carbohydrate moiety. This mAb A6 A E4-reactive protein was neither expressed
      on cell surface nor released outside the bacteria; immunogold electron microscopy
      showed that these antigens were localized in the cytoplasma area.

PMID- 7581276
TI  - Immunochemical characterisation and epitope mapping of a novel fimbrial protein
      (Pg-II fimbria) of Porphyromonas gingivalis.
AB  - Mouse monoclonal antibody (mAb) Pgf-II specific for a 72-kDa major cell-surface
      protein (72K-CSP) derived from Porphyromonas gingivalis OMZ 409 was prepared.
      Immunoblotting analysis revealed that mAb Pgf-II reacted with 72K-CSP but not
      with 41-kDa fimbrial subunit protein (41K-fimbrilin) derived from P. gingivalis
      381. Electron microscopic observation revealed that P. gingivalis OMZ 409
      possessed peritrichous, thin fimbriae on their surface. Immunogold electron
      microscopy also demonstrated that mAb Pgf-II bound to the 72K-CSP examined with
      the gold particles arranged along the fibril array originating from the cell
      surface of the bacteria. These findings suggested that P. gingivalis 72K-CSP was
      identifiable as another fimbriae (termed Pg-II fimbriae) different from the
      fimbriae (termed Pg-I fimbriae) composed of a 41K-fimbrilin. Using multipin
      peptide synthesis technology, 102 sequential overlapping peptides covering the
      entire 514 amino-acid stretch of Pg-II fimbriae were synthesised. Seven
      immunodominant regions within Pg-II fimbrial protein molecule, which definitely
      reacted with the serum of patients with periodontal diseases, were detected.

PMID- 7581277
TI  - Missionaries and the early development of nursing in China.
AB  - By the late 1930s, nursing, which had come into being in China in the 1880s, had
      developed into a profession represented by a well-organized national association
      with a membership of 6,000, which was continuously expanding by hundreds of new
      recruits trained at nearly 200 nursing schools all over the country. The progress
      was remarkable. In retrospect, we can easily discern the outstanding contribution
      made by the Western medical missionaries. To the latter's dedication, the
      profession owed its birth and its incipient growth in particular. Trained
      missionary nurses, following in the footsteps of missionary pioneers, penetrated
      into all parts of the country to start dispensaries and hospitals literally from
      nothing. In 1923, China had 53 percent of the missionary hospital beds and 48
      percent of the missionary doctors in the world. Missionary nurses constituted 32
      percent of the total number of nurses in China in 1923 and their number reached a
      peak of nearly 700 in 1927. Although the number of medical missionaries,
      physicians, and nurses was tiny compared to the size of the nation's population,
      and although their interest in "healing the sick" aimed to serve their primary
      goal of "saving the soul," their contribution to nursing development in China,
      especially their efforts in training native nurses at numerous missionary
      hospitals and nursing schools, can hardly be overestimated. Derived from
      missionary involvement was another important contributor to the rapid progress of
      nursing: the Nurses' Association of China. Born in a critical stage of nursing
      development in the country, the NAC organized the profession and regulated its
      training through sponsoring registration, holding examinations, and developing a
      standard required curriculum. Essentially, it played the role of a great
      organizer and paved the way for the further growth of the profession. Coming from
      a totally different culture, missionaries had to overcome a lot of difficulty to
      adapt themselves to the environment in China. The problems they encountered
      varied from place to place. Geographically, the interior areas were more prone to
      antiforeign and anti-Christian feelings, whereas the coastal areas were,
      comparatively, more receptive to new ideas and techniques brought by Western
      missionaries. Fluctuating with the political developments in China, the
      missionaries' cause peaked when the nation welcomed them following the quelling
      of the Boxer upheaval and the overthrow of the dynastic monarchy, and ebbed when
      xenophobia or nationalism ran high in any form of massive political
      turmoil.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7581278
TI  - Agnes Karll and the creation of an independent German nursing association, 1900
      1927.

PMID- 7581279
TI  - The diary as historical evidence. The case of Sarah Gallop Gregg.

PMID- 7581281
TI  - Backrubs vs. Bach. Nursing and the entry-into-practice debate, 1946-1986.

PMID- 7581280
TI  - The historical relationship of nursing program accreditation and public policy in
      Canada.

PMID- 7581282
TI  - "We are left so much alone to work out our own problems". Nurses on American
      Indian reservations during the 1930s.

PMID- 7581283
TI  - Satisfied to carry the bag. Three black community health nurses' contributions to
      health care reform, 1900-1937.

PMID- 7581284
TI  - The origins of modern nursing in The Netherlands.

PMID- 7581285
TI  - Linda Richards and nursing in Japan, 1885-1890.

PMID- 7581286
TI  - Biokinetics and absorption of actinides in human volunteers: a review.
AB  - Experiments that have been described in the literature are reviewed, with
      emphasis on the techniques that have been used, rather than a critical appraisal
      of the results obtained.

PMID- 7581287
TI  - Radon concentrations in spa water taken from hot and cold springs in Taiwan.
AB  - Spa water samples taken from hot and cold springs throughout Taiwan were analyzed
      for waterborne radon concentrations using electret ion chambers. The highest
      radon concentration was detected at Yangmingshan National Park, where it is
      closed to the action level of 11.0 kBq m-3. Next comes a sea-water hot spring at
      Green Isle on the east coast of Taiwan. The spa water used by the nearby
      inhabitants may increase the indoor radon concentration by a factor of two in
      extreme cases.

PMID- 7581288
TI  - EPR dating CO2- sites in tooth enamel apatites by ENDOR and triple resonance.
AB  - In this work we combine electron paramagnetic resonance (EPR), high-resolution
      electron nucleus double resonance (ENDOR) and general triple resonance (GTR)
      spectroscopies, to study the local environment of the CO2- groups created by
      ionizing radiation in fossil tooth enamel. We demonstrate that the CO2- groups
      occupy slightly modified phosphate sites in the hydroxyapatite lattice. In
      quaternary shark enamel we found these groups to be interacting with water
      molecules in the apatite channels. The absence of water molecules as first
      neighbors in mammalian samples indicate, however, that these molecules are not
      significantly responsible for the stabilization of CO2- dating centers in enamel.

PMID- 7581289
TI  - Synthesis of [18F]NNC 12-0817 and [18F]NNC 12-0818; two potential radioligands
      for the dopamine transporter.
AB  - The preparation of no-carrier-added 18F labelled NNC 12-0817 (1-(2-[bis(4
      fluorophenyl)methoxy]ethyl)-4-[4-oxo-4-(2- thienyl)butyl]piperazine) and NNC 12
      0818 (1-(2[bis(4- fluorophenyl)methoxy]ethyl)-4-]4-hydroxy-4-(2
      thienyl)butyl]piperazine) is described. NNC 12-0818 is the designation of the
      racemic mixture of two enantiomers. Fluorine-18 is introduced into 4-[18F]fluoro
      4'-fluorobenzophenone from the corresponding triflate salt by a nucleophilic
      aromatic substitution reaction. A no-carrier-added synthesis was performed in 6
      steps starting from N,N-dimethylaniline and 4-fluorobenzoyl chloride giving
      [18F]NNC 12-0817 and [18F]NNC 12-0818 in good yields and a radiochemical purity
      after HPLC-purification higher than 99%.

PMID- 7581291
TI  - Radioactivity in marine fish of the Bay of Bengal.
AB  - The concentrations of natural radionuclides of 40K, 232Th and 238U and artificial
      radionuclides of 137Cs and 134Cs in different marine fish samples from the Bay of
      Bengal were determined. In some of the fish samples contamination of the 137Cs
      radionuclide was observed, but 134Cs was below detection level.

PMID- 7581290
TI  - Development of a simple and selective separation of 67Cu from irradiated zinc for
      use in antibody labelling: a comparison of methods.
AB  - A procedure for the production and separation of Cu isotopes from irradiated Zn
      was developed. Following a comparison of methods based on extraction,
      electrolysis and ion-exchange chromatography, a technique for the separation of
      Cu employing three ion-exchange matrices was developed which was simple,
      reproducible and hot cell-compatible. The specific activity of the final product
      was 37 MBq 67Cu/microgram Cu at EOB. The level of impurities was so low that no
      interference with antibody labelling was observed.

PMID- 7581292
TI  - Analysis of 10B by PIGE with factor analytical gamma-ray peak identification.
AB  - Studying the biodistribution of boronated compounds for B neutron capture therapy
      (BNCT) requires the accurate detection of low levels of boron (10B) in biological
      samples. Proton induced gamma-ray emission analysis (PIGE) of 10B was found to be
      viable in a study of low density lipoprotein (LDL), in tissue and blood samples.
      However, the method is sensitive to Na present in the samples and can therefore
      not be used for accurate measurements of 10B concentrations below 5 ppm in
      samples containing Na. PIGE can be considered to be an appropriate reference
      method for chemical B analysis. The factor analytical method presented here is
      the most objective way to separate Na and B peaks from each other, and the
      factorizing method can be applied in different forms of spectral analysis.

PMID- 7581293
TI  - Synthesis of 5-HT3 receptor antagonists, [11C]Y-25130 and [11C]YM060.
AB  - Two high-affinity 5-HT3 receptor ligands, Y-25130 and YM 060, have been labeled
      with 11C for use in PET studies to measure 5-HT3 receptors. The [11C]Y-25130 was
      prepared by N-methylation of nor-Y-25130-BH3 complex with [11C]CH3I in the
      presence of K2CO3 followed by HCl hydrolysis. Likewise, N-methylation of nor
      YM060 gave [11C]YM060. After HPLC separation, the decay-corrected radiochemical
      yield of the two 11C-labeled ligands was 34-40% based on [11C]CH3I, the specific
      activity was 10-12 GBq/mumol at 35-40 min from EOB, and the radiochemical and
      chemical purities were > 99%. In mice, the brain uptake of the two compounds was
      the lowest among the tissues investigated, but the level of the brain
      radioactivity increased with time.

PMID- 7581294
TI  - Neurotrophin-induced modulation of synaptic transmission in the adult
      hippocampus.
AB  - The NGF-family of neurotrophic factors including NGF, BDNF and NT-3,4/5 is known
      to be crucial for neuronal survival and differentiation during development.
      However, recent studies suggest that the neurotrophins are also widely expressed
      and play a dynamic role in the mature nervous system. One of the major sites of
      expression of the neurotrophins in the adult brain is the hippocampus which has
      been also popular as an important structure for the adult plasticity. Moreover,
      the level of expression of the neurotrophins in the hippocampus can be regulated
      by a variety of neuronal inputs, such as experimentally-induced seizures,
      injection of glutamate receptor agonists, and LTP-inducing stimulation. The
      possibility that the neurotrophins modulate synaptic transmission in the mature
      brain has been investigated at the Schaffer collateral-CA1 synapses in the adult
      rat hippocampus. We report that transient application of BDNF and NT-3, but not
      NGF induces a long-lasting increase of synaptic transmission, which is likely to
      be mediated by Trk family of receptor tyrosine kinases. Both BDNF and NT-3
      decrease paired pulse facilitation, suggesting a possible presynaptic
      modification. Interestingly, previous potentiation of synaptic activity by the
      application of neurotrophic factors does not occlude the induction of long-term
      potentiation. These results suggest that the neurotrophins may locally regulate
      synaptic plasticity in the adult nervous system.

PMID- 7581295
TI  - Spatial synaptic integration in Purkinje cell dendrites.
AB  - Synaptic integration occurs within a framework of synaptic connections, and cell
      type-specific, intrinsic and transmitter-gated ion channels. These components are
      differentially distributed over the somato-dendritic membrane. Recent results
      from Purkinje cells and pyramidal cells exemplify some of these mechanisms of
      spatial synaptic integration. This paper focusses on the cerebellar Purkinje
      cell. In these neurons, the amplitude and distribution of single climbing fibre
      and parallel fibre EPSP-evoked Ca2+ influx were regulated by the transient
      outward, IA-like current in the distal (spiny) dendrites. The synaptically evoked
      Ca2+ influx was graded from a local response involving only a few terminal spiny
      dendrites to a propagated Ca2+ spike. The climbing fibre-evoked Ca2+ influx in
      the spiny dendrites was finely graded by parallel fibre-induced depolarization.
      Climbing fibre and parallel fibre-evoked Ca2+ influx elicited a short lasting
      afterhyperpolarization that affected subsequent dendritic Ca2+ influx. In
      addition, inhibitory synaptic input controlled dendritic Ca2+ influx. Interaction
      between information from different sources along the dendrites is thus controlled
      by intrinsic potassium conductances and IPSPs. Different electrophysiological
      properties are found in the cerebellar neurons. Thus, Golgi cells, stellate cells
      and granule cells seem to integrate on a shorter intrinsic timescale than do
      Purkinje cells, the output neuron of the cerebellar cortex. The specific
      mechanisms by which different types of presynaptic neurons specifically innervate
      a given dendritic compartment remain to be elucidated, but recent results provide
      some experimental evidence of a differential distribution of cell adhesion
      molecules between the axonal and the somato-dendritic membrane, suggesting one
      mechanism contributing to the ordered distribution of synapses during
      synaptogenesis.

PMID- 7581296
TI  - Using paired-pulse facilitation to probe the mechanisms for long-term
      potentiation (LTP).
AB  - Paired-pulse facilitation (PPF) of excitatory synaptic transmission at Schaffer
      collateral synapses in the hippocampus was examined in relationship to long-term
      potentiation (LTP). PPF is a relatively simple-to-measure presynaptic form of
      synaptic plasticity. It is hypothesized that if the expression of LTP includes a
      presynaptic component, then PPF and LTP may interfere with one another. When
      averaged over more than 100 experiments, we observed no change in average PPF
      with LTP, as reported previously by a number of investigators. When individual
      experiments were analyzed, however, PPF significantly increased or decreased with
      LTP in direct relation to the initial value of PPF. There was also a linear
      relationship between the change in PPF and the magnitude of LTP. The PPF changes
      were specific to LTP and presynaptic in origin as they were input-specific and
      persisted with low concentrations of CNQX, GABAA and GABAB antagonists, different
      interstimulus intervals, and different Ca2+ concentrations. To understand the
      interaction between LTP and PPF, we constructed a simple model of LTP in which
      potential contributions by increases in three synaptic parameters were examined:
      the number of neurotransmitter release sites (n), the probability of release (p),
      and the postsynaptic unit potential (q). The data were fit by a model in which
      there were increases in n that changed the average p of the population, but not
      by a model that increased p or q alone. This is the first experimental evidence
      for an increase in the number of release sites with LTP, which could be due to
      pre- or postsynaptic mechanisms.

PMID- 7581297
TI  - Long-term regulation of short-term plasticity: a postsynaptic influence on
      presynaptic transmitter release.
AB  - The dynamics of presynaptic transmitter release are often matched to the
      physiological properties and function of the postsynaptic cell. Evidence in
      organisms as diverse as the cricket central nervous system and the cat spinal
      cord suggests that retrograde signaling is essential for matching presynaptic
      release properties to the postsynaptic cell. The cricket central nervous system
      is favorably organized for analysis of synaptic function in the central nervous
      system. Several lines of independent evidence suggest that it is possible to
      reliably estimate the size of single quantal release events at the sensory to
      interneuron synapses of the cricket. A quantal analysis suggests that a
      retrograde influence on the probability of presynaptic release is responsible for
      matching presynaptic dynamic properties to postsynaptic targets. This retrograde
      interaction is hypothesized to be a long-term modification on the basal
      probability of presynaptic release.

PMID- 7581298
TI  - The metallo-proteinase activity of tetanus and botulism neurotoxins.
AB  - Tetanus and botulinum neurotoxins are produced by several Clostridia and cause
      the paralytic syndromes of tetanus and botulism by blocking neurotransmitter
      release at central and peripheral synapses, respectively. They consist of two
      disulfide-linked polypeptides: H (100 kDa) is responsible for neurospecific
      binding and cell penetration of L (50 kDa), a zinc-endopeptidase specific for
      three protein subunits of the neuroexocytosis apparatus. Tetanus neurotoxin and
      botulinum neurotoxin serotypes B, D, F and G cleave at single sites, which differ
      for each neurotoxin, VAMP/synaptobrevin, a membrane protein of the synaptic
      vesicles. Botulinum A and E neurotoxins cleave SNAP-25, a protein of the
      presynaptic membrane, at two different carboxyl-terminal peptide bonds. Serotype
      C cleaves specifically syntaxin, another protein of the nerve plasmalemma. The
      target specificity of these metallo-proteinases relies on a double recognition of
      their substrates based on interactions with the cleavage site and with a non
      contiguous segment that contains a structural motif common to VAMP, SNAP-25 and
      syntaxin.

PMID- 7581299
TI  - Mechanisms of synaptogenesis in hippocampal neurons in primary culture.
AB  - To improve our understanding of the mechanisms which regulate the formation and
      the functional maturation of synaptic contacts between neurons, we used
      hippocampal neurons maintained in primary cultures as experimental system. In
      this model, which offers several advantages for the study of neuronal development
      and synaptogenesis, we investigated some of the cellular mechanisms underlying
      the formation of presynaptic and postsynaptic compartments.

PMID- 7581300
TI  - Signalling synapse formation between identified neurons.
AB  - We have investigated the signals between identified leech neurons during the
      formation of specific synapses in culture. At an inhibitory serotonergic synapse
      between two well-studied neurons, the postsynaptic cell has an additional
      (extrasynaptic) excitatory response to 5-HT which may underly a form of activity
      dependent modulation. Thus, the presynaptic neuron must select which 5-HT
      response will be activated and which will be excluded at its synapses. The
      selection of these responses preceded synapse formation and was specifically
      induced at sites of contact with the presynaptic neuron, this not being observed
      for other cell pairings. Aldehyde-fixed presynaptic cells were equally effective,
      unless pre-treated with trypsin or wheat germ agglutinin, suggesting that contact
      with a specific cell-surface glycoprotein induced this physiological change in 5
      HT sensitivity. The mechanism underlying the selective loss of the extrasynaptic
      response has been examined by single channel recording. Cation channels in the
      postsynaptic neuron were modulated by protein kinase C (PKC) upon binding of 5-HT
      to a 5-HT2 receptor. However, at sites of contact with the presynaptic neuron,
      the channels were no longer sensitive to PKC. Furthermore, when cation channels
      from uncontacted neurons were inserted or 'crammed' into contacted neurons, they
      were rapidly rendered insensitive to PKC, demonstrating a cytoplasmic signal for
      the uncoupling of channel modulation. Interestingly, the cytoplasm of contacted
      postsynaptic neurons showed immunoreactivity for tyrosine phosphorylation:
      exposure of the neurons to specific inhibitors of tyrosine kinases prevented
      tyrosine phosphorylation, the loss of cation channel modulation and synapse
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581302
TI  - Autoantibodies, neurotoxins and the nervous system.
AB  - Myasthenia gravis, the Lambert-Eaton myasthenic syndrome, and acquired
      neuromyotonia are three disorders of the neuromuscular junction or motor nerve
      that are caused by autoantibodies to ion channel proteins: acetylcholine
      receptors, voltage-gated calcium channels and voltage-gated potassium channels,
      respectively. The antibody titres can be measured using the relevant 125I
      neurotoxins to label the extracted channels. Other disorders of the peripheral
      motor nerve are associated with antibodies to gangliosides. Sera with raised
      levels of anti-ganglioside antibodies have direct effects on the function of the
      distal motor nerve and motor nerve terminal. These conditions can be improved by
      therapies designed to reduce circulating antibodies. Antibodies that bind to
      neuronal surface antigens are proving to be of great clinical importance and
      interest in neurological disorders.

PMID- 7581301
TI  - Inositol trisphosphate and cyclic ADP ribose as long range messengers generating
      local subcellular calcium signals.
AB  - The process of messenger-mediated release of Ca2+ from intracellular stores,
      which is of great importance in virtually all cell types including neurons, can
      best be studied in cells lacking voltage-gated Ca2+ channels in the plasma
      membrane. In pancreatic acinar cells agonist-evoked repetitive cytosolic Ca2+
      spikes are due to release of Ca2+ via inositoltrisphosphate (IP3) and ryanodine
      receptors and reuptake into the stores via thapsigargin-sensitive Ca2+ pumps. At
      low acetylcholine (ACh) or cholecystokinin concentrations the cytosolic Ca2+
      spikes are mostly confined to the secretory granule area of the polarized
      pancreatic acinar cells. Similar results can be obtained by intracellular
      infusion of IP3 (or one of its non-metabolizable analogues) or cyclic ADP ribose.
      This suggests that high affinity IP3 and ryanodine receptors are concentrated in
      the secretory granule area. We have generated an 'artificial synapse' on isolated
      acinar cells by having a cell-attached patch pipette filled with ACh on the basal
      membrane. Initially, ACh is prevented from making contact with the receptors by
      the negative potential applied to the pipette. When the pipette polarity is
      switched to positive ACh can bind to its receptors. Using digital Ca2+ imaging it
      could be seen that the first cytosolic rise often occurred in the secretory
      granule area, a considerable distance away from the site of the agonist-receptor
      interaction. This shows the long-range action of the messenger(s) IP3 and or
      cyclic ADP ribose generated by the ACh-receptor interaction. The local Ca2+
      spikes in the secretory granule area are sufficient for exocytotic secretory
      responses as seen in capacitance measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581303
TI  - Overexpression of choline acetyltransferase reconstitutes discrete acetylcholine
      release in some but not all synapse formation-defective neuroblastoma cells.
AB  - Secretion of acetylcholine (ACh) in neuroblastoma cells overexpressing choline
      acetyltransferase (ChAT) was examined. With transient transfection of ChAT cDNA,
      neuroblastoma cells, which have no endogenous ChAT and either adhere to myotubes
      or not, failed to form functional synapses, and thus no evidence for release of
      ACh was detected. Stable neuroblastoma cell lines overexpressing ChAT accumulated
      ACh inside the cell, and slowly released ACh to the outside of the cell in a
      calcium-independent fashion. However, after co-culturing them with rat muscle
      cells, these transformed cells adhered to myotubes and ACh was secreted in a
      discrete fashion into the synaptic cleft efficiently in some neuroblastoma cell
      lines but rather inefficiently in another cell line. The results show that the
      latent secretion machinery of ChAT overexpressing neuroblastoma cells either is
      competent or possess defect(s) in ACh release.

PMID- 7581304
TI  - Mediatophore and other presynaptic proteins. A cybernetic linking at the active
      zone.
AB  - In rapidly transmitting synapses, the mediatophore, a protein located in the
      presynaptic membrane, seems to play a key role in the last step of transmitter
      release. Reconstituted either in proteoliposomes or in Xenopus oocytes, or
      transfected in particular cell lines, the mediatophore is able to release
      acetylcholine with characteristics which meet several typical features of
      transmitter release in natural synapses. Good correspondence between the two
      conditions was found for: i) the dependency of release upon calcium
      concentration; ii) the desensitisation of release by persistence of internal
      calcium; iii) the effect of several drugs; iv) the fleeting formation of a
      population of large intramembrane particles during the precise time of release;
      and v) the pulsatile or quantal nature of transmitter release. All these features
      therefore could well be ascribed to intrinsic properties of the mediatophore
      molecule. How is the mediatophore integrated in the whole presynaptic apparatus?
      To what extent is its function regulated by the other proteins of the active
      zone? These questions are far from being solved. We want nevertheless to propose
      here a general view in which characteristic presynaptic functions such as
      transmitter release, calcium entry, sequestration and extrusion, regulation of
      short- and long-term changes in release efficiency, are supported by an ordered
      succession of molecular events involving the proteins of the active zone. It will
      be seen that some proteins compete for a common binding site. It is thus expected
      that they will occupy this site in a regulated succession, according to simple
      cybernetic rules.

PMID- 7581305
TI  - The role of non-quantal release of acetylcholine in regulation of postsynaptic
      membrane electrogenesis.
AB  - In mammalian nerve-muscle preparations treated with an anticholinesterase, the
      acetylcholine (ACh) released non-quantally (NQR) reaches the postsynaptic
      receptors and causes a small depolarization of the membrane potential at the
      endplate region of the muscle fibres. Increase in quantal release potentiates the
      NQR and vice versa, the amplitude and the kinetic parameters of quantal miniature
      endplate currents (MEPCs) change during manipulation of NQR, indicating direct
      interaction between both types of release. Repetitive binding of ACh to
      postsynaptic receptors which prolongs the time course of MEPCs in anti
      cholinesterase-treated endplates leads within 1-2 h to progressive
      desensitization in the presence of non-quantal release and to the subsequent
      shortening of the quantal responses. We have also investigated the effect of
      procedures known to modulate non-quantal acetylcholine release, on the small, but
      obvious, difference in the resting membrane potential between the endplate zone
      and other areas of the mouse muscle fibre. The resting membrane potential at the
      endplate zone with intact cholinesterase is more negative (by 2-4 mV) than in the
      endplate-free area. The experiments were performed to test the hypothesis that
      the hyperpolarization is caused by an electrogenic Na(+)-K+ pump operating during
      the action of ACh released in non-quantal form. Observations in favour of this
      idea are that both short-term denervation (which eliminates non-quantal but not
      quantal release) and ouabain abolish the local synaptic hyperpolarization and
      that subsequent application of low doses of ACh restores it. It follows,
      therefore, that the hyperpolarization is probably caused by a small but
      continuous ACh leakage from the nerve terminal.

PMID- 7581306
TI  - Calcium binding sites of the transmitter release mechanism: clues from short-term
      facilitation.
AB  - The binding of multiple, probably four, calcium ions to an intraterminal protein
      is believed to be an integral step in the gating of neurotransmitter release. We
      have reexamined the clues to this ion-protein interaction inferred from
      experimental results on transmitter release and its facilitation. It is argued
      that while one of the four calcium binding sites required to activate transmitter
      release may have a relatively low affinity, results obtained from studies on
      short-term facilitation suggest that the other sites have affinities that range
      from intermediate to relatively high. A low calcium affinity should not,
      therefore, be regarded as obligatory requirement in the identification of the
      calcium binding protein.

PMID- 7581307
TI  - McMahon Medical Clinic, 1972-1992.

PMID- 7581308
TI  - A comparison of the writings of Sir William Osler and his exemplar, Sir Thomas
      Browne.
AB  - Sir William Osler was known throughout his life as a great humanitarian. His
      writings touched all of us, and to persons of every race, creed, and color, he
      showed universal feelings of justice and mercy. Osler's writing supports great
      tolerance for all, yet Osler's contemporaries were far less broad-minded and not
      free of bigotry. Osler's role model, Sir Thomas Browne, wrote openly about his
      marked prejudices against Catholics, Jews, Moslems, and even women. This paradox
      between Osler's tolerance and humanitarianism and the prejudice and bigotry of
      his time, as well as his role model Browne, are explored.

PMID- 7581309
TI  - Homicide deaths in New York City.

PMID- 7581310
TI  - Failure of birth data to predict early school difficulties among inner-city first
      graders.

PMID- 7581311
TI  - Injury prevention in an urban setting: challenges and successes.
AB  - The Harlem Hospital Injury Prevention Program (HHIPP) was established in 1988
      with the goal of reducing injuries to children in central Harlem by providing
      safe play areas, supervised activities, and injury prevention education. To
      achieve this goal, a broad-based coalition was formed with state and local
      governmental agencies interested in injury prevention and with community groups,
      schools, parents, and hospital staff. An evaluation of the program in terms of
      both process and outcome formed a critical element of this effort. Since 1988 the
      HHIPP, as the lead agency for the Healthy Neighborhoods/Safe Kids Coalition,
      developed or participated in two types of programs: injury-prevention education
      programs and programs that provide safe activities and/or environments for
      children. The educational programs included Window Guards campaign; Safety City
      Program; Kids, Injuries and Street Smarts Program (KISS); Burn Prevention
      Curriculum and Smoke Detector Distribution; Harlem Alternative to Violence
      Program; Adolescent Outreach Program; and Critical Incident Stress Management
      Teams. The safe activities and environmental programs included the Bicycle Safety
      Program/Urban Youth Bike Corps; Playground Injury Prevention Program; the
      Greening of Harlem Program; the Harlem Horizon Art Studio; Harlem Hospital Dance
      Clinic; Unity through Murals project; baseball at the Harlem Little League;
      winter baseball clinic; and the soccer league. Each program was conceived using
      injury data, coupled with parental concern and activism, which acted as catalysts
      to create a community coalition to respond to a specific problem. Data systems
      developed over time, which monitored the prevalence and incidence of childhood
      injuries in northern Manhattan, including central Harlem, became essential not
      only to identify specific types of childhood injuries in this community but also
      to evaluate these programs for the prevention of injuries in children.

PMID- 7581312
TI  - Gunshot violence in the United States: a growing threat to all. A physician's
      personal view.

PMID- 7581313
TI  - Violence as a public health issue.
AB  - Violence--homicides, suicides, injuries caused by youth or family acts--continues
      in the United States. Firearms are involved in most incidents. The Centers for
      Disease Control and Prevention addresses the problem using the traditional tools
      of public health: epidemiologic data, individual and societal interventions based
      on the data, and ongoing evaluations to assess the effects of the interventions
      and change them if necessary. Examples of interventions are presented.

PMID- 7581314
TI  - Violence among children and adolescents and the role of the pediatrician.
AB  - Violence has reached epidemic proportions in the United States and has become the
      single most important public health problem affecting adolescent males. It is
      believed that violence and its subsequent morbidity and mortality have a
      multifactorial origin, including developmental factors, gang involvement, access
      to firearms, drugs, the media, poverty, and family violence. Pediatricians have a
      critical role in reducing violence through early identification of family
      violence, education and counseling to decrease well-known risk factors, and
      provision of nonviolent problem-solving and coping strategies to children, youth,
      and their families. It is essential that we initiate preventive measures now
      rather than be paralyzed by the weight of the crisis.

PMID- 7581316
TI  - Community service as an integral component of undergraduate medical education:
      facilitating student involvement.
AB  - Urban poverty, of which New York City has the highest incidence, is associated
      with unmet needs and inappropriate use of emergency rooms and hospitals.
      Community-based medical practitioners can ameliorate these situations. Medical
      students from New York City-area schools often are willing to help. The New York
      Academy of Medicine instituted an Urban Health Initiative to coordinate student
      and faculty involvement in community service and to emphasize the social
      responsibilities of medicine. The experience may provide a model for integrating
      community service into medical school curricula.

PMID- 7581315
TI  - Perceived risks and benefits of alcohol, cigarette, and drug use among urban low
      income African-American early adolescents.
AB  - Perceptions about drugs and the social environment may be important influences on
      cigarette, alcohol and drug use, yet little is known regarding the perspective of
      early adolescent boys and girls, especially among minority urban youths. Among
      351 African-American low-income urban youth, 9 through 15 years of age,
      completing a community-based computerized questionnaire, 25% acknowledged
      alcohol, cigarette, and/or illicit drug use in the past 6 months; 19% expected to
      use one of those substances in the next 6 months. Family exposure to drugs
      increased the likelihood that youths expected to use drugs by factors of 4.5
      (boys) and 2.5 (girls). Other factors (feelings about drugs, community drug use,
      long-term expectations) distinguished users from nonusers or had different
      associations with use in boys and girls. Gender-specific perceptions about drugs
      may have the potential to be modified in drug and substance use prevention
      programs.

PMID- 7581317
TI  - Home care in the urban setting--a challenge to medical education.
AB  - The rapid growth in the use of the home as the site of care delivery necessitates
      that the home setting be incorporated as a teaching site into the curriculum of
      medical schools. Urban medical schools have a unique advantage in that they have
      a large population base readily available to students and preceptors as well as
      an array of allied health providers. Urban institutions can be in the forefront
      of developing programs that simultaneously promote: clinically competent care;
      the maximal function of large numbers of acutely and chronically ill persons;
      research into issues of cost-effectiveness; and, most importantly, professional
      humanism. Specific educational objectives are included.

PMID- 7581318
TI  - The ends of medicine: shaping new goals.

PMID- 7581319
TI  - Analysis of a repeat-containing family of Giardia lamblia variant-specific
      surface protein genes: diversity through gene duplication and divergence.
AB  - Giardia lamblia trophozoites express on their surfaces one of a set of cysteine
      rich antigenically variant proteins, called variant-specific surface proteins,
      which comprise the majority of proteins detected by surface labeling. While these
      VSP proteins may be immunodominant proteins important in the host immune response
      to G. lamblia, the ability to switch expression from one VSP to another may
      provide a means for the trophozoites to avoid the host immune response. The first
      VSP characterized, VSPA6 (from the A6 clone of the WB isolate, originally termed
      CRP170), contains 18-23 copies of a 65 amino acid repeat. We have now used the
      repeat as a probe to isolate from a WBA6 genomic library two genes related to
      vspA6 (called vspA6-S1, vspA6-S2). Sequence analysis of the vspA6-S1 gene
      revealed nearly two complete copies of the 195 bp repeat and substantial
      nucleotide and translated amino acid similarity in the coding regions 5' and 3'
      to the repeats. The vspA6-S2 gene, while still related, showed greater divergence
      from vspA6 than vspA6-S1 in the nonrepeat coding region and contained nearly four
      copies of a 201 bp repeat that was 75% identical to the 195 bp vspA6 repeat.
      These results suggest that gene duplication followed by divergence has played a
      key role in the generation of the vsp gene repertoire.

PMID- 7581320
TI  - Calcium and hydrogen ion concentrations in the parasitophorous vacuoles of
      epithelial cells infected with the microsporidian Encephalitozoon hellem.
AB  - Microsporidia of the genus Encephalitozoon undergo merogony and sporogony in a
      parasitophorous vacuole within the host cell. Cultured green monkey kidney cells
      infected with Encephalitozoon hellem were loaded with the fluorescent dyes fura-2
      or BCECF in order to measure intracellular concentrations of calcium and hydrogen
      ions respectively. Both the parasitophorous vacuole calcium concentration and pH
      values resembled those of the host cell cytoplasm in infected cells. Calcein
      entered the parasitophorous vacuole but not other host cell vacuoles or parasite
      stages within the parasitophorous vacuole. The lack of a pH or calcium
      concentration gradient across the parasitophorous vacuole membrane and the
      permeability of this membrane to a large anion such as calcein suggest that the
      vacuole membrane surrounding E. hellem resembles that surrounding some other
      intracellular parasites such as Toxoplasma gondii. A potential role is discussed
      for the parasitophorous vacuole calcium concentration in germination in situ.

PMID- 7581321
TI  - Transmissibility of bacterial endosymbionts between isolates of Acanthamoeba spp.
AB  - Experimental transmission of two bacterial endosymbionts to symbiont-free
      isolates of Acanthamoeba spp. was studied to determine specificity of the host
      symbiont relationship. Both symbionts originated from amoebic isolates displaying
      an identical mitochondrial DNA EcoRI fingerprint (group AcUW II). Symbioses were
      readily established in one amoebic isolate which displayed a homologous mtDNA
      fingerprint (group AcUW II). Exposure of a heterologous amoebic isolate (group
      AcUW IV) to the two symbionts resulted in either cell death or encystation
      without the establishment of symbioses. While symbioses were established with an
      amoebic isolate from a second heterologous group (AcUWI), a unique membranous
      sheath appeared and persisted around one of the symbionts which did not exist in
      the original host. An isolate representing a third heterologous amoebic group
      (AcUW VI) was variable in its susceptibility with one symbiont unable to infect
      the host and the other becoming established only after an initial reaction in
      which trophozoites rounded-up and floated off the substrate. These studies
      suggest that a specific recognition system exists between particular isolates of
      Acanthamoeba and their symbionts, and that the appearance of a killer phenotype
      is related to contact between mismatched though recognized, pairs.

PMID- 7581322
TI  - Identification and partial purification of a stage-specific 33 kDa mitochondrial
      protein as the alternative oxidase of the Trypanosoma brucei brucei bloodstream
      trypomastigotes.
AB  - The glycerophosphate oxidase (GPO), the unique terminal oxidase of bloodstream
      trypanosome (TAO), appears to be functionally similar to the alternative oxidases
      of some plants and higher fungi. Immunoblotting of mitochondrial proteins of
      bloodstream trypomastigotes of Trypanosoma brucei with monoclonal or polyclonal
      antibodies to Sauromatum guttatum (voodoo lily) and Symplocarpus foetidus (skunk
      cabbage) alternative oxidases respectively revealed two proteins of about 33 kDa
      (p33) and 68 kDa (p68). These proteins are not present in procyclic
      trypomastigotes. Electrophoresis under rigorous denaturing conditions indicated
      p68 to be the dimer of p33. Indirect immunofluorescent studies of bloodstream and
      procyclic trypomastigotes with monoclonal antibody to plant alternative oxidase
      also showed the localization of 33 kDa protein in the mitochondria of the
      bloodstream trypomastigotes. The functional TAO activity could be solubilized
      efficiently from the mitochondrial membrane of the bloodstream trypomastigotes by
      1% NP-40 or 10 mM lauryl maltoside. When fractionated by Superose 12 gel
      filtration chromatography, p33 was co-purified with the TAO enzymatic activity.
      The apparent molecular size of the active enzyme complex was found to be 160 kDa.
      Gradual disappearance of the 33 kDa protein and the TAO enzymatic activity were
      well correlated during in vitro differentiation of the bloodstream to procyclic
      trypomastigotes. This study implies that the net biosynthesis of p33, an
      essential subunit of TAO, is decreased during differentiation from bloodstream to
      procyclic trypomastigotes.

PMID- 7581323
TI  - Molecular comparison of the mitochondrial and cytoplasmic hsp70 of Trypanosoma
      cruzi, Trypanosoma brucei and Leishmania major.
AB  - We compared the expression and localization of the mitochondrial and cytoplasmic
      hsp70 of the protozoans Trypanosoma cruzi, Trypanosoma brucei and Leishmania
      major. The mitochondrial protein is encoded by multiple mRNA in all species,
      while the cytoplasmic protein is encoded by a single mRNA. In all three species,
      the mitochondrial hsp70 is concentrated in the kinetoplast, a submitochondrial
      structure that houses the unusual DNA (kDNA) that characterizes this group of
      organisms, while the cytoplasmic protein is distributed throughout the cell.
      These results suggest that, in all kinetoplastid species, mt-hsp70 has a specific
      function in kDNA biology, possibly in the processes of kDNA replication, RNA
      editing or kinetoplast structure.

PMID- 7581325
TI  - A simple, efficient technique for freezing Tetrahymena thermophila.
AB  - We have developed a simple, efficient procedure for the long term freezing of
      Tetrahymena thermophila in liquid nitrogen. This technique yields excellent
      recovery of viable cells with all strains tested and does not require the use of
      a controlled rate low temperature freezer. To optimize the freezing technique, we
      have examined the effects of varying a number of parameters, including the
      physiological state of the cells prior to freezing, the time of exposure to
      cryoprotectant, and the rate of freezing and thawing. The frequency of viable
      cell recovery following freezing using this technique has been tested for a
      variety of different cell lines.

PMID- 7581324
TI  - Short-term in vitro culture and molecular analysis of the microsporidian,
      Enterocytozoon bieneusi.
AB  - The microsporidium, Enterocytozoon bieneusi, causes a severe, debilitating,
      chronic diarrhea in patients with the acquired immunodeficiency syndrome.
      Specific diagnosis of intestinal microsporidiosis, especially due to
      Enterocytozoon, is difficult and there is no known therapy that can completely
      eradicate this parasite. Preliminary studies indicate that a short term (about 6
      months) in vitro culture of this parasite yielding low numbers of spores, may be
      established by inoculating human lung fibroblasts and/or monkey kidney cell
      cultures with duodenal aspirates and or biopsy from infected patients. The
      cultures may subsequently be used for the isolation and molecular analysis of
      parasite DNA.

PMID- 7581326
TI  - Henneguya adherens n. sp. (Myxozoa, Myxosporea), parasite of the Amazonian fish,
      Acestrorhynchus falcatus.
AB  - A new species of myxosporean from the gill filaments of the freshwater teleost
      fish, Acestrohynchus falcatus collected in the Amazon river is described from
      light and transmission electron microscope observations. The mature spores (total
      length 32.3 [30.7-35.1] micron) and all developmental stages were found in the
      same sporogonic plasmodium. The ellipsoidal spore body consists of 2 unequal
      shell valves adhering together along the suture lines. Each valve, tapering as a
      caudal projection, forms a long tail (length 20.5 [18.0-21.7] micron). The tail
      was surrounded by a homogeneous sheath on its length. The polar capsules
      measuring 3.1 x 1.2 micron contain 3-4 coils of the polar filament. All surfaces
      of the immature and mature spores were surrounded by a closely adherent
      homogenous structural sheath, mainly thicker around the tails. The taxonomic
      affinities of this parasite to other species are discussed.

PMID- 7581327
TI  - Encephalitozoon-like organisms in patients with alveolar hydatid disease: cell
      culture, ultrastructure, histoimmunochemical localization and seroprevalence.
AB  - We found Encephalitozoon-like organisms in an in vitro culture of a human liver
      lesion which was due to larval Echinococcus multilocularis. The organisms
      developed in the same fashion as an Encephalitozoon cuniculi. The spores that
      developed in parasitophorous vacuoles were 2.0-2.6 x 1.1-1.5 microns; each
      contained a single nucleus and 4-5 polar tubule coils, closely resembling E.
      cuniculi in its ultrastructure. Mature spores were collected from the
      supernatants by the use of Percoll centrifugation resulting in the banding of the
      spores on continuous gradients. We prepared three sorts of spores which were
      different in buoyant density in 0.15 M NaCl: 1.05-1.07 g/ml spores, 1.12 g/ml
      spores, and spores of over 1.14 g/ml. Polyclonal antibodies to a pool of each
      spore preparation were produced in a rabbit and applied to the detection of
      microsporidian antigen in situ. The histoimmunoperoxidase (HIP) procedure was
      used to detect the microsporidian antigen in echinococcal liver lesions from
      patients with alveolar hydatid disease (AHD). Ten echinococcal liver lesions from
      different AHD patients were examined and four were found to be positive in the
      HIP test. The Percoll-separated spores were also used as an antigen to detect for
      antibodies in the sera from the patients with AHD by Western blotting. Antibodies
      were detected in 62 (52%) of the 119 AHD patients and in only 8 (5%) of the 159
      normal healthy individuals.

PMID- 7581329
TI  - Small subunit ribosomal DNA phylogeny of various microsporidia with emphasis on
      AIDS related forms.
AB  - Phylogenetic analysis of the small subunit ribosomal DNA of a broad range of
      representative microsporidia including five species from humans (Enterocytozoon
      bieneusi, Nosema corneum, Septata intestinalis, Encephalitozoon hellem and
      Encephalitozoon cuniculi), reveals that human microsporidia are polyphyletic in
      origin. Septata intestinalis and E. hellem are very similar to the mammalian
      parasite E. cuniculi. Based on the results of our phylogenetic analysis, we
      suggest that S. intestinalis be designated Encephalitozoon intestinalis.
      Furthermore, analysis of our data indicates that N. corneum is much more closely
      related to the insect parasite Endoreticulatus schubergi than it is to other
      Nosema species. This finding is supported by recent studies which have shown a
      similarity between E. schubergi and N. corneum based on the origin and
      development of the parasitophorous vacuole. Thus these opportunistic
      microsporidian parasites can originate from hosts closely or distantly related to
      humans. Finally, the phylogeny based on small subunit ribosomal DNA sequences is
      highly inconsistent with traditional classifications based on morphological
      characters. Many of the important morphological characters (diplokaryon,
      sporophorous vesicle, and meiosis) appear to have multiple-origins.

PMID- 7581328
TI  - Primers designed for amplification of Echinococcus multilocularis DNA amplify the
      DNA of Encephalitozoon-like spores in the polymerase chain reaction.
AB  - Microsporidian spores were developed from cells which were grown in vitro from a
      human liver lesion which was due to larval Echinococcus multilocularis. The
      microsporidian spores developed in the same fashion as an Encephalitozoon
      cuniculi. The Encephalitozoon-like spores were completely separated on Percoll
      gradients. The separated spores contained DNA capable of amplification by two
      different primer sets designed for the polymerase chain reaction (PCR) of E.
      multilocularis DNA. However, the cell DNA from which microsporidium developed was
      thoroughly insensitive to the PCR using the E. multilocularis primer sets. The
      results strongly suggested that Encephalitozoon should be taken into
      consideration, when DNA isolated from larval E. multilocularis is analyzed.

PMID- 7581330
TI  - Membrane skeletal proteins and their integral membrane protein anchors are
      targets for tyrosine and threonine kinases in Euglena.
AB  - Proteins of the membrane skeleton of Euglena gracilis were extensively
      phosphorylated in vivo and in vitro after incubation with [32P]-orthophosphate or
      gamma-[32P] ATP. Endogenous protein threonine/serine activity phosphorylated the
      major membrane skeletal proteins (articulins) and the putative integral membrane
      protein (IP39) anchor for articulins. The latter was also the major target for
      endogenous protein tyrosine kinase activity. A cytoplasmic domain of IP39 was
      specifically phosphorylated, and removal of this domain with papain eliminated
      the radiolabeled phosphoamino acids and eliminated or radically shifted the PI of
      the multiple isoforms of IP39. In gel kinase assays IP39 autophosphorylated and a
      25 kDa protein which does not autophosphorylate was identified as a
      threonine/serine (casein) kinase. Plasma membranes from the membrane skeletal
      protein complex contained threonine/serine (casein) kinase activity, and cross
      linking experiments suggested that IP39 was the likely source for this membrane
      activity. pH optima, cation requirements and heparin sensitivity of the detergent
      solubilized membrane activity were determined. Together these results suggest
      that protein kinases may be important modulators of protein assembly and function
      of the membrane skeleton of these protistan cells.

PMID- 7581331
TI  - Intracellular localization of LRV1 in infected Leishmania cells and epitope
      conservation of the coat protein.
AB  - Polyclonal antibodies were raised against a recombinant fragment of the coat
      protein of LRV1-1 to determine the epitope conservation of the coat protein among
      LRV1 isolates, and the intracellular localization of LRV1 particles in
      promastigote cells of Leishmania braziliensis. Western blot analysis showed that
      specific epitopes of the coat protein are highly conserved among isolates from
      different geographic areas. Using indirect immunofluorescence assays LRV1 viral
      particles were observed as fluorescent granules, limited to the cytoplasm and
      with no apparent association to the host organelles or the cell membrane,
      characteristic of a persistent, non-infectious virus.

PMID- 7581332
TI  - The Louis S. Diamond Festschrift.

PMID- 7581333
TI  - Axenic cultivation of Entamoeba dispar Brumpt 1925, Entamoeba insolita Geiman and
      Wichterman 1937 and Entamoeba ranarum Grassi 1879.
AB  - Three species of Entamoeba have been grown in axenic culture for the first time.
      In two cases, novel methods for adapting the organisms to growth without bacteria
      were employed. While E. ranarum was axenized by the classic technique of Diamond,
      from a monoxenic culture with Trypanosoma cruzi as the associate, both E. dispar
      and E. insolita were first grown in axenic culture medium supplemented with
      lethally irradiated bacteria. From there, E. insolita was axenized directly, but
      E. dispar initially required the presence of fixed bacteria. After prolonged
      culture under this technically axenic but unwieldy culture system, E. dispar was
      eventually adapted to growth in the absence of added bacteria.

PMID- 7581334
TI  - Primary structure of the hydrogenosomal malic enzyme of Trichomonas vaginalis and
      its relationship to homologous enzymes.
AB  - The complete nucleotide sequence has been established for two genes (maeA and
      maeB) coding for different subunits of the hydrogenosomal malic enzyme [malate
      dehydrogenase (decarboxylating) EC 1.1.1.39] of Trichomonas vaginalis. Two
      further genes (maeC and maeD) of this enzyme have been partially sequenced. The
      complete open reading frames code for polypeptides of 567 amino acids in length.
      These two open reading frames are similar with less than 12 percent pairwise
      nucleotide differences and less than 9 percent pairwise amino acid differences.
      The open reading frames of the two partially sequenced genes correspond to the
      amino-terminal part of the polypeptides coded and are similar to the
      corresponding parts of the completely sequenced ones. The deduced translation
      products of the two complete genes differ in their calculated pI values by 1.5 pH
      unit. The genes code for polypeptides which contain 12 or 11 amino-terminal amino
      acyl residues not present in the proteins isolated from the cell. Other
      hydrogenosomal enzymes also have similar amino-terminal extensions which probably
      play a role in organellar targeting and translocation of the newly synthesized
      polypeptides. A comparison of 19 related enzymes from bacteria and eukaryotes
      with the maeA product revealed 34-45 percent amino acid identity. Phylogenetic
      reconstruction based on nonconservative amino acid differences with maximum
      parsimony (phylogenetic analysis using parsimony, PAUP) and distance based
      (neighbor-joining, NJ) methods showed that the T. vaginalis enzyme is the most
      divergent of all eukaryotic malic enzymes, indicating its long independent
      evolutionary history.

PMID- 7581335
TI  - Giardia lamblia: identification and characterization of a variant-specific
      surface protein gene family.
AB  - Giardia lamblia trophozoites undergo antigenic variation by modulating the
      expression of variant-specific surface proteins (VSP), which are encoded by a
      number of small multigene families. We characterized the genomic copy of the VSP
      gene expressed by the cloned trophozoite line H7, derived from the isolate GS/M,
      in addition to a related, but nonexpressed, family member. The coding regions of
      the two genes encode closely related polypeptides (86% identity). However,
      differences in the coding region of these genes reside solely in an 873 bp
      segment. Only four differences were found between the 5' flanking sequences (465
      bp). The proximal 205 base pairs downstream from the coding regions were
      identical, but thereafter the sequences diverged (37% identity over the next 391
      bp). Mapping studies indicated that no other VSP gene was located within 4 kb
      pairs of the expressed H7 VSP gene, and transcripts from the nonexpressed gene
      were detected in neither GS/H7 nor heterogeneous trophozoites populations derived
      from this cloned line. Any mechanisms responsible for the differential expression
      of VSP genes must reconcile the near identity of DNA sequences that flank the
      coding regions of expressed and nonexpressed VSP genes.

PMID- 7581337
TI  - Lipophosphoglycan is present in distinctly different form in different Entamoeba
      histolytica strains and absent in Entamoeba moshkovskii and Entamoeba invadens.
AB  - Lipophosphoglycan has recently been demonstrated on the cell surface of Entamoeba
      histolytica strain HM-1:IMSS. A monoclonal antibody against this molecule had
      failed to react with some other strains of E. histolytica, including the strain
      Rahman. To determine if a structurally distinct lipophosphoglycan existed in
      Rahman, [3H]galactose-labeled glycoconjugates were electrophoresed through sodium
      dodecyl sulfate polyacrylamide gel electrophoresis. The electrophoretic pattern
      in Rahman was very different compared to that obtained with strains HM-1:IMSS and
      200:NIH. A number of experiments including sensitivity to mild acid, nitrous acid
      and phosphoinositol-specific phospholipase C suggest that the Rahman
      glycoconjugate is indeed a lipophosphoglycan-like molecule but distinctly
      different from that of HM-1:IMSS. Mild acid-treated glycoconjugates from Rahman
      and HM-1:IMSS revealed the presence of neutral trisaccharides and monosaccharides
      in Rahman but not in HM-1:IMSS. Human immune sera from amoebiasis patients and a
      polyclonal antibody against HM-1:IMSS lipophosphoglycan both recognized Rahman
      glycoconjugate. Thus, while lipophosphoglycan molecules from the two strains
      share common epitopes, they are clearly distinct from each other. Molecules
      bearing resemblance to lipophosphoglycan could not be detected in other Entamoeba
      species, namely Entamoeba invadens and Entamoeba moshkovskii.

PMID- 7581336
TI  - Elucidation of the DNA synthetic cycle of Entamoeba spp. using flow cytometry and
      mathematical modeling.
AB  - We developed a method to study the DNA synthetic cycles of Entamoeba histolytica
      and Entamoeba invadens by flow cytometry (FCM) based on a preparative procedure
      to reduce both high levels of natural fluorescence and non-specific adsorption of
      fluorochromes. We modeled G1, S, and G2 phases as a series of overlapping
      Gaussian curves. Both E. histolytica and E. invadens displayed G1, S, and G2
      proportions that are consistent with eukaryotic cell populations in exponential
      or stationary growth phase. Exponential phase E. histolytica populations
      contained a hypodiploid subset with a mass of about 20% less than the diploid
      value which we estimate by FCM to be 24 x 10(-14) g DNA/cell. Exponential phase
      E. invadens populations contained a hypodiploid subset with a mass of about 6%
      less than the diploid value which we estimate by FCM to be 30 x 10(-14) g
      DNA/cell.

PMID- 7581339
TI  - Molecular cloning and characterization of a Leishmania donovani alpha-tubulin
      gene.
AB  - We have isolated a cDNA for an alpha-tubulin mRNA from L. donovani promastigotes
      and determined its complete nucleotide sequence. Both nucleotide and deduced
      amino acid sequence analysis of this cDNA showed significant similarity with a
      previously reported, partial sequence of an L. enriettii alpha-tubulin and the
      complete sequence of human alpha-tubulin. Further, the in vitro translated L.
      donovani alpha-tubulin gene product was specifically immunoprecipitated with a
      monoclonal antibody against human alpha-tubulin. Northern blot analysis revealed
      that there was little change in the expression of the L. donovani alpha-tubulin
      RNA during parasite differentiation from promastigote to the in vitro grown
      "amastigote" form. Southern blot analysis revealed a simple genomic organization
      for the L. donovani alpha-tubulin gene with more than one copy of the alpha
      tubulin gene in the parasite genome. To our knowledge, this is the first complete
      sequence of an alpha-tubulin for Leishmania to be reported in the literature.

PMID- 7581338
TI  - A lipoprotein-cholesterol-albumin serum substitute stimulates Giardia lamblia
      encystation vesicle formation.
AB  - We found previously that the A6 clone of Giardia lamblia strain WB that did not
      encyst in vitro was blocked at an early stage in differentiation, as it did not
      form encystation secretory vesicles (ESV) efficiently or express cyst antigens,
      in comparison with the related clone C6. We now report that A6 formed ESV
      normally in the suckling mouse model. Therefore, we asked whether our serum
      containing encystation media might lack a stimulus or component or contain an
      inhibitor of ESV formation to which A6 was especially sensitive. We found that
      replacing bovine serum with a lipoprotein-cholesterol solution and bovine serum
      albumin (LPC) in pre-encystation and encystation media increased ESV formation by
      both A6 and C6. The % of A6 cells with ESV increased from 8% in BS medium to 48%
      in LPC medium, compared with 64% and 98% for C6. Similarly, the average number of
      ESV/positive cell increased from 1.5 in BS medium to 7.7 in LPC medium for A6,
      and from 13.3 to 19.7 for C6. Moreover, in LPC encystation media, A6 expressed
      the cyst wall epitope recognized by monoclonal GCSA-1. Although formation of
      water-resistant cysts by A6 was increased > 60 fold in LPC media, the numbers of
      cysts remained only approximately 3-15% that of C6. This suggests that LPC may
      primarily affect early events in encystation and that A6 may require additional
      factors later in encystation.

PMID- 7581340
TI  - The primary structure of an Entamoeba histolytica beta-hexosaminidase A subunit.
AB  - An Entamoeba histolytica gene (hex-A1) that encodes subunit A of the lysosomal
      enzyme beta-hexosaminidase has been cloned and sequenced. The inferred 59 kDa hex
      A1 protein has the same molecular weight and 32% amino acid residue identity with
      the human and mouse proteins and 28% residue identity with the Dictyostelium
      protein. Northern blot analysis identified a mRNA of approximately 1.6 kb, which
      is in agreement with the expected size of a mRNA encoding the 522 amino acid hex
      A1 protein. Southern blot analysis indicated the presence of at least two beta
      hexosaminidase A subunit genes.

PMID- 7581341
TI  - Identification of immunogenic epitopes of the 170-kDa subunit adhesin of
      Entamoeba histolytica in patients with invasive amebiasis.
AB  - Entamoeba histolytica causes amebic dysentery (AD) and liver abscess (ALA).
      Little is known about protective immunity to amebiasis, and studies in this area
      have been complicated by the paucity of defined ameba antigens. We examined the
      proliferative responses of peripheral blood mononuclear cells (PBMC) from
      patients with AD and ALA to a recombinant protein containing a portion of the 170
      kDa adhesin of E. histolytica (170CR), and to two synthetic peptides (1 and 2)
      derived from the 170 kDa sequence that were predicted to contain T cell epitopes.
      A significant number of patients with AD and ALA had PBMC that proliferated to
      170CR molecule, and several individuals with ALA and AD had T cells that
      recognized one or both peptides. Contrarily, individuals from a non-endemic
      region for amebiasis did not respond to 170CR protein, or to both peptides. In
      regard to antibody response, nine of fifteen patients with ALA showed antibodies
      to 170CR protein. These same patients had antibodies to peptide 2. We identified
      peptides from 170-kDa adhesin that may contain both T and B cell epitopes
      recognized by some patients with invasive amebiasis. These peptides may be
      valuable reagents in studies of the immune response to amebiasis.

PMID- 7581342
TI  - Trichomonas vaginalis: ultrastructural bases of the cytopathic effect.
AB  - The in vitro cytopathic effect of Trichomonas vaginalis on epithelial cells was
      explored through the interaction of trophozoites of the virulent strain GT-10
      with MDCK monolayers. The interaction was analyzed through electrophysiology,
      video microscopy, and transmission and scanning electron microscopy. Electrical
      measurements revealed that living parasites produced severe damage to the cell
      monolayers within 30 min, manifested as a rapid decrease in transepithelial
      resistance. Microscopic observations demonstrated that when placed in contact
      with epithelial cells, trichomonas formed clumps through interdigitations and
      transient plasma membrane junctions between adjacent parasites. Also, attached
      trophozoites adopted an ameboid shape. The in vitro cytopathic action of T.
      vaginalis on MDCK cells was initially evident by modifications of the plasma
      membrane, resulting in opening of tight junctions, membrane blebbing, and
      monolayer disruption. After 15 min of interaction the damage was focal,
      concentrating at sites where parasite clumps adhered to the monolayer. At 30 min
      practically all MDCK cells were dead, whether or not trichomonas were attached to
      them. These events were followed by detachment of lysed cells and complete
      disruption of the monolayer at 60 min. Electron microscopy demonstrated a
      peculiar form of adhesion that appears to be specific for trichomonas, in which
      the basal surface of T. vaginalis formed slender channels through which
      microvilli and cytoplasmic fragments of epithelial cells were internalized. The
      same sequence of lytic events was found with the less virulent GT-3 strain.
      However, the time course of cytolysis with GT-3 parasites was much slower, and
      lysis was limited to areas of attachment of T. vaginalis.

PMID- 7581343
TI  - Phenomenon of sight.
AB  - Since the beginning of time, the eye has been a symbol of special significance
      and intrigue. Albeit a small organ, the visual functions of the eye are
      controlled by approximately one third of the cerebral cortex of the brain and, in
      the visual, the spiritual, and the literary arts the eye has added a note of
      realism to individuals lives.

PMID- 7581344
TI  - Deemed status accreditation of nonhospital-based ambulatory surgery centers.
AB  - Ambulatory surgery is a fast expanding arena for health care delivery.
      Reimbursement for services is required for continued existence, and reimbursement
      is directly related to accreditation. However, at the present time only hospitals
      receive automatic recognition from Medicare for voluntary accreditation efforts.
      This article defines and describes the many regulatory agencies that impact on
      the ability to obtain accreditation. Deemed status for freestanding ambulatory
      care facilities is examined.

PMID- 7581345
TI  - Giant cell arteritis.
AB  - Giant cell arteritis (GCA) is an autoimmune condition with a predilection for the
      arteries of the head and neck. Because GCA may lead to permanent blindness,
      stroke, or death, it is critically important for all health care personnel, in
      particular ophthalmic nurses, to know about the presentation, diagnostic methods,
      and treatment modalities related to this disease. Prompt intervention may save a
      life.

PMID- 7581346
TI  - Nursing care of the choroidal melanoma patient.
AB  - A patient diagnosed with choroidal melanoma presents the ophthalmic nurse with a
      unique opportunity to practice one of the most challenging aspects of clinical
      and psychosocial nursing care. Although choroidal melanoma is a treatable cancer,
      this tumor has the ability to increase in size, to metastasize, and to cause
      death.

PMID- 7581347
TI  - Perioperative considerations of glaucoma.
AB  - Perioperative nurses need to have a basic understanding of the anatomy of the
      globe and the physiological effects of the intraocular pressure from glaucoma.
      Surgical procedures are implemented initially for closed-angle (acute) and
      congenital glaucoma because of the emergent status of the diagnosis. The patient
      with open-angle (chronic) glaucoma may have a prolonged medical treatment before
      the need for surgical procedures.

PMID- 7581348
TI  - Corneal transplant: a new lease on life.
AB  - Penetrating keratoplasty can afford some patients an opportunity to regain their
      vision. The perioperative nurse plays a vital role in the care of these special
      patients. A thorough perioperative plan of care, based on an understanding of the
      procedure, is key to a successful corneal grafting.

PMID- 7581349
TI  - Perioperative care of the vitreo-retinal patient.

PMID- 7581351
TI  - Post-concussion syndrome and the coping hypothesis.
AB  - Neuropsychological functioning and level of subjective symptomatology was
      assessed in 15 adults at 2 weeks, 1 month, and 3 months post-concussion.
      Performance by the concussion subjects was compared to the results obtained by a
      matched group of normal controls. At 2 weeks post-injury the concussion subjects
      had deficits in intellectual, attentional, memory, and language abilities.
      Visuospatial constructional abilities were relatively preserved. Concussed
      subjects also reported high levels of disturbance in affective, cognitive, and
      social functioning. By 3 months post-injury the concussed subjects were still
      displaying deficits in attentional and language functioning. The level of
      subjective symptoms reported by the concussed subjects was not significantly
      different from that reported by controls. Results provide some support for the
      'coping hypothesis' explanation of post-concussion syndrome.

PMID- 7581350
TI  - The evolution of the clinician-scientist model of neurological rehabilitation.
AB  - Over the past three or four decades two treatment technologies have been evolving
      in parallel, recently to some extent merging. The first of these technologies is
      behaviour analysis, with its emphasis on identification and manipulation of
      variables external to the individual as controlling agents. The second is
      neurological rehabilitation, with a characteristic focus of resources on recovery
      of function following neurological damage. The histories of both of these
      technologies are similar in that they emerged from basic laboratory research with
      non-human subjects, followed by extension of findings to research with humans,
      culminating in widespread formal application of results. The past 5 years have
      seen a convergence of behaviour analytic and neurological rehabilitation
      techniques resulting in major shifts in treatment service delivery systems. We
      briefly chronicle the emergence of these two technologies from their basic
      underpinnings through world-wide use. Further, discussion is provided describing
      our and others' experience with the combining of behaviour and neurological
      rehabilitation. Finally, we give an account of an innovative neurological
      rehabilitation service delivery system designed to deliver effective cost
      efficient treatment in the patient's natural environment. Implicit in the design
      and implementation of this real-world model of rehabilitation is the combination
      of behavioural technology and neurological rehabilitation towards the achievement
      of functional outcomes which endure. Our purpose in the above is to provide an
      introduction to present use and future potential of behaviour analytic
      methodologies and technologies in rehabilitation.

PMID- 7581352
TI  - Analysis of demographic and functional subacute (transitional) rehabilitation
      data.
AB  - Demographic and functional data were obtained on 102 patients from three subacute
      rehabilitation units specializing in low-level traumatic brain injury (TBI)
      patients. Functional assessment evaluation was performed using the Disability
      Rating Scale (DRS). The average admission and discharge DRS scores were 17.4 and
      13.6, respectively. On average this patient population improved from an extremely
      severe level of disability to a severe level. The TBI patient subset improved on
      average from 20.4 to 13.1. Significant correlation exists between admission,
      discharge, and differential DRS scores, as has been demonstrated previously in
      the evaluation of this scale among only TBI patients. No significant correlation
      was demonstrated between demographic information and DRS scores. Thus, no
      demographic predictors of good or bad functional outcome were identified. In
      addition, analyses of relationships between diagnosis, length of stay, and age
      will provide information about subactute rehabilitation, an emerging but little
      studied branch of rehabilitation medicine.

PMID- 7581353
TI  - Depression among the head-injured and non-head-injured: a discriminant analysis.
AB  - Neuropsychologists often use traditional psychological tests to assess depression
      following a head injury; but the assumption that depression with a head injury
      resembles that in an uninjured person is suspect. The current study attempts to
      examine the cognitive manifestations of depression with and without a coexisting
      head-injury. Advanced statistical methods are used to assess whether or not the
      two depressions 'look alike' with respect to the neuropsychological sequelae of
      the disorders. A total of 1182 people were entered into one of two discriminant
      function analyses (DFA) for depression. Each person was a member of one of the
      following groups: (a) depressed, (b) non-depressed, (c) head-injured, or (d) head
      injured and depressed. Two functions were performed for depression, one on the
      population of head-injured people and one on the population of uninjured people.
      Cross-validations were performed for each population and across populations in
      order to assess the utility of each population's function for the opposite group.
      This comparison allows the researcher to indirectly compare depression in the two
      populations. Both functions were successfully applied to either population when
      MMPI variables were included in the analyses. However, when only cognitive
      variables were included the function performed on the non-head-injured population
      did not correctly classify head-injured people as depressed or non-depressed. One
      explanation for this is that the range of cognitive scores in head-injured people
      is so great that it allows for a less accurate but more generalizable function.
      Suggestions for future research are discussed.

PMID- 7581354
TI  - Behavioural training during acute brain trauma rehabilitation: an empirical case
      study.
AB  - Operant conditioning-based behavioural interventions are commonly used for the
      behavioural problems of individuals with mental retardation. There is also
      growing evidence of the benefits of these interventions for treating some of the
      behavioural problems of individuals with acquired cognitive deficits resulting
      from brain trauma. However, the effects of behavioural interventions on
      behavioural problems occurring during acute neurorehabilitation, when orientation
      and memory are most impaired, have not been studied. In this empirical case
      study, operant conditioning-based procedures were applied with an 8-year-old girl
      recovering from brain trauma and related neurosurgery. Screaming, non-compliance
      and aggression, which were disrupting rehabilitation therapies and follow-up
      neuroimaging, were treated using differential positive reinforcement techniques.
      Beneficial behavioural intervention effects were demonstrated using single
      subject experimental methods. Aberrant behaviour during physical and occupational
      therapies was reduced, and cooperation with a computerized tomography (CT) scan
      without sedation was accomplished using operant behavioural intervention. Results
      support the use of operant interventions early in recovery from brain trauma, and
      highlight the importance of interdisciplinary collaboration for the
      implementation and further study of early behavioural interventions.

PMID- 7581355
TI  - The long-term outcome of head injury: implications for service planning.
AB  - As most of those experiencing traumatic brain injury tend to be young, disabled
      survivors will be gradually accruing in each locality as each year passes. How
      many need continuing care a decade after injury? How many need day care, or need
      help with finding work, or continuing support for carers? 190 patients who had
      been admitted to two UK regional neurosurgical units on average some 7 years
      earlier were followed up. With an average age of 29 years these patients stayed
      in hospital for an average 33 days. At follow-up 23% were classified as having
      moderate disability or worse on the Glasgow Outcome Scale, including 7.4% who had
      died subsequent to discharge. Survivors were given a neuropsychological
      assessment and a socioeconomic interview. Of the survivors, 17% had failed to
      make a good recovery, but 36% were failing to occupy their time in a meaningful
      way. Age over 30 at time of injury, not occupied before injury, and above-average
      length of stay were some of the predictors for failing to occupy time. Quality of
      life was severely curtailed for those who could not occupy their time, as was the
      case for their carers. Appropriate counselling, vocational evaluation and family
      support in the early years following injury may help to improve quality of life
      for both the head-injured person and their carers.

PMID- 7581356
TI  - Coping and psychosocial function after brain injury.
AB  - A total of 74 brain-injured patients and 46 non-neurological matched controls
      consecutively admitted to a specialist medical rehabilitation unit were
      administered the 'Ways of Coping' checklist and the 'Headley Court psychosocial
      rating scale'. The relatives of all participants were sent the psychosocial
      rating scale. An analysis of the 'Ways of Coping' checklist showed the brain
      injured patients used four strategies for coping, namely problem-focused, emotion
      focused, avoidance, and wishful thinking. Correlations between these four factors
      and the responses on the 'Headley Court psychosocial rating scale' showed that
      less use of emotion-focused, avoidance, and wishful thinking coping strategies
      predicts better psychosocial functioning in the brain-injured group, a result
      similar to those reported for a wide variety of other health problems. The
      implications for treatment and management are discussed.

PMID- 7581357
TI  - Reality orientation training in an amnesic: a controlled single-case study (n =
      572 days).
AB  - 'Reality orientation training' (ROT) is a well-established therapy used with the
      elderly, especially those with dementia. It aims to improve orientation and
      reduce negative behaviours, e.g. confusion. ROT has been recommended for non
      demented patients with acquired neurological impairment. However, this suggestion
      has not been investigated further in controlled trials. This paper describes an
      informal 24 h ROT programme with an amnesic subject (H.J.). It combined single
      case experimental designs derived from behaviour therapy. Target behaviours were
      items of temporal orientation--current time/time of day, year, season, month and
      day of week. Orientation regarding the current date was not trained, and thus
      served as control variable for non-specific effects (e.g. spontaneous recovery).
      In order to improve oriented behaviour in different relevant situations outside
      the clinic, we chose 24 h ROT instead of formal therapeutic sessions. The
      patients' spouse offered 24 h ROT at home 7 days a week. This consisted of
      reminding the patient of orientation information, e.g. the current day of the
      week in different situations. Furthermore, negative behaviours such as irrelevant
      questions were ignored. The patients' spouse was trained and supervised to carry
      out this task in 27 sessions each lasting 10 min. For 14 weeks supervision was
      provided twice a week in the clinic (i.e. 2 x 10 min). Afterwards the spouse
      continued to apply ROT at home without further supervision in two follow-up
      periods. As expected, learning was slow but reliable. Generalization of
      improvement to another setting was shown (home vs clinic). Stable therapeutic
      gains over a long follow-up period could be demonstrated.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7581358
TI  - Brain injury without head injury after multiple trauma.
AB  - Watershed infarction has previously been described after cerebral trauma, when it
      is due to raised intracranial pressure or systemic hypotension. A case is
      reported, so far as is known for the first time, of bilateral watershed
      infarction following blunt systemic trauma, without injury to the head or neck.
      The importance of resuscitation in preventing secondary brain injury caused by
      systemic hypotension is highlighted. The advantages of HMPAO-SPET in detecting
      cerebral perfusion defects are discussed.

PMID- 7581359
TI  - Recent advances in the neuropsychology of human olfaction and anosmia.
AB  - Patients' olfactory functioning is rarely considered by rehabilitation
      specialists because this capacity is seen as unnecessary for most vocational and
      academic purposes. However, several recent studies have shown that intermittent
      exposure to fragrances can help subjects sustain attention more efficiently. As
      this effect is especially pronounced when subjects report attention-maintenance
      difficulties, accessory olfactory stimulation may enhance the sustained attention
      capacities of head-injured subjects. Another study is cited in which subjects who
      lost their sense of smell following head injuries were found to experience more
      difficulty in maintaining employment. This effect is probably related to orbital
      lobe damage, which usually accompanies post-traumatic anosmia. The implications
      of these studies for rehabilitation professionals are discussed.

PMID- 7581361
TI  - Expression of full-length and truncated dystrophin mini-genes in transgenic mdx
      mice.
AB  - Duchenne and Becker muscular dystrophy are caused by defects in the dystrophin
      gene, and are candidates for treatment by gene therapy. We have shown previously
      that overexpression of a full-length dystrophin cDNA prevents the development of
      dystrophic symptoms in mdx mice. We show here that this functional correction can
      be achieved by expressing the full-length muscle isoform at a lower level than is
      present in control animals. Gene therapy for DMD may necessitate the use of
      truncated dystrophin mini-genes to accommodate the limited cloning capacity of
      current-generation viral delivery vectors. We have constructed both murine and
      human mini-genes deleted for exons 17-48, and have demonstrated that expression
      of either mini-gene can almost completely prevent the development of dystrophic
      symptoms in transgenic mdx mice. These results suggest that viral-mediated
      expression of moderate levels of a truncated dystrophin could be an effective
      treatment for DMD.

PMID- 7581360
TI  - Expression of human full-length and minidystrophin in transgenic mdx mice:
      implications for gene therapy of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a
      high spontaneous mutation rate and no effective treatment, hence development of
      genetic based therapies is an important goal. We report that expression of a
      recombinant human minidystrophin cDNA, compatible with current viral vectors, can
      significantly reduce the myopathic phenotype in transgenic mdx mice, even when
      expressed at only 20-30% of endogenous dystrophin levels at the sarcolemma. To
      the extent that data obtained in mouse studies are applicable to DMD, the virtual
      elimination of morphological and biochemical abnormalities in the mdx mouse
      supports the use of this cDNA in somatic gene therapy protocols for DMD.

PMID- 7581362
TI  - Comparison of the positional cloning methods used to isolate the BRCA1 gene.
AB  - A critical step in positional cloning is the identification of candidate genes
      from a large, genetically defined region. Candidate gene isolation by hybrid
      selection, genomic sequencing, and direct cDNA library screening identified 45
      candidate gene fragments (CGFs) from a 600 kb genomic region that contains the
      BRCA1 gene. These CGFs define a minimum of 15 genes, six of which are newly
      localized to the BRCA1 region. We present an analysis of the efficiency and the
      sequences generated for each of these methods. We also compare our CGF set to
      those reported for the BRCA1 region by three other groups, revealing a surprising
      lack of overlap among the sets.

PMID- 7581363
TI  - On unequal allelic expression of the neurofibromin gene in neurofibromatosis type
      1.
AB  - The autosomal dominantly inherited disease neurofibromatosis type 1 (NF1) is
      caused by mutations of a large gene comprising 59 exons, which code for a protein
      with 2818 amino acids called neurofibromin. Employing an expressed polymorphic
      site in exon 5 of the neurofibromin gene, the expression of its alleles was
      analysed quantitatively by scanning radioactive RT-PCR fragments of this exon
      prepared from the RNA of fibroblast cell cultures from 15 NF1 patients and of
      white blood cells from one NF1 patient. Thirteen of the RNA preparations yielded
      unequal amounts of the allelic messages. The deviations of the expression ratios
      (A2:A1) from 1.0 ranged from -0.9 to +25.8. The allelic messages were equally
      represented in the RNA preparations from five informative healthy donors. Apart
      from fibroblasts this phenomenon could also be detected in keratinocytes,
      melanocytes from normally pigmented skin and melanocytes from a cafe-au-lait spot
      of one patient. Only one of three patients affected by stop mutations exhibited
      unequal allelic expression. When nuclear RNA from 10 of the 13 patients was
      examined, equal amounts of the primary transcripts were found (average ratio
      A2/A1: 1.08 +/- 0.07 S.E.M.), indicating that unequal expression on the level of
      mRNA was not caused by mutations affecting transcriptional regulation. The ratio
      of the amount of neurofibromin to that of p120 GAP did not seem to be correlated
      with the extent of unequal allelic expression.

PMID- 7581365
TI  - A large deletion together with a point mutation in the GALC gene is a common
      mutant allele in patients with infantile Krabbe disease.
AB  - Galactocerebrosidase (GALC) activity is deficient in all patients with globoid
      cell leukodystrophy (GLD). While most patients have the severe infantile form of
      this autosomal recessive disorder (Krabbe disease), patients up to 50 years of
      age have been diagnosed in this laboratory. With the cloning of the GALC cDNA and
      availability of information regarding the gene organization, patients can be
      evaluated for their disease-causing mutations. We now report that a large
      deletion, together with a polymorphic C to T transition at position 502 of cDNA
      (counting from the A of the initiation codon), is responsible for a large number
      of disease-causing alleles in patients with Krabbe disease. Of 48 patients
      evaluated, 10 were found to be homozygous for the 502/del allele, five patients
      were heterozygous for this allele, 21 patients were heterozygous for the 502
      mutation (presence of the deletion could not be confirmed), and one infantile
      patient was homozygous for the 502 mutation but at least one allele was not
      deleted. No patient was found to have the deletion without the 502 polymorphism.
      The delineation of mutations causing infantile Krabbe disease will provide new
      information regarding structure-function relationships in this multi-subunit
      enzyme and will improve the identification of patients and carriers in some
      families.

PMID- 7581364
TI  - Allelic association and deletions in autosomal recessive proximal spinal muscular
      atrophy: association of marker genotype with disease severity and candidate
      cDNAs.
AB  - The candidate region for spinal muscular atrophy (SMA) has been defined as a 750
      kb interval on 5q13. In this study, we performed allelic association studies in
      154 German SMA families with the multicopy markers Ag1-CA (D5S1556); C212
      (D5F149S1/S2) and correlated genotype data with deletion of candidate genes. Both
      multicopy markers recognize 0-3 alleles pro chromosome. Deletions were detected
      for all copies of the markers Ag1-CA (C272) and C212 in 13 of 88 (15%) type I SMA
      patients and three of 48 (6%) type II patients. In all informative cases, the
      deletion was inherited from one parent. In two further cases (one type I and one
      type III SMA), de novo deletions of only one copy of Ag1-CA and C212 were found.
      In both cases the patients were homozygously deleted for the survival motor
      neuron (SMN) gene (exons 7 and 8) but only the type I SMA patient was deleted for
      the neuronal apoptosis inhibitory protein (NAIP) gene (exons 5 and 6). A third
      case (type II SMA) showed de novo deletion of SMN, but not of Ag1-CA, C212 and
      NAIP. Specific alleles of Ag1-CA and C212 showed significant association with
      SMA, particularly in type I SMA. When the number of marker copies defines
      genotypes, 1,1 (one allele on each chromosome) is found to be increased in type I
      SMA (50%) and 1,2 (one allele on one chromosome and two alleles on the other one)
      in type II SMA (60%). The 2,2 genotype (two alleles on each chromosome) was found
      in 4% of type I and II patients. By comparison, pooled normal genotype
      frequencies were 20, 44 and 36%, respectively. These results suggest a strong
      correlation between genotype and severity of disease. Based on these data we
      propose a model which indicates that type I SMA patients are composed of two
      severe alleles, type II of a mild and a severe, and type III of two mild alleles.
      Correlation of Ag1-CA genotype with deletion of the XS2G3/NAIP genes indicates
      that most patients with a deletion have a 1,1 genotype. Owing to the physical
      proximity of these markers, we propose that a large deletion occurs on type I SMA
      chromosomes that removes DNA between C212 and XS2G3/NAIP and that type II SMA
      results from compound heterozygosity for mild (small deletion) and severe
      mutations.

PMID- 7581366
TI  - Model for a transcript map of human chromosome 21: isolation of new coding
      sequences from exon and enriched cDNA libraries.
AB  - The construction of a transcriptional map for human chromosome 21 requires the
      generation of a specific catalogue of genes, together with corresponding mapping
      information. Towards this goal, we conducted a pilot study on a pool of random
      chromosome 21 cosmids representing 2 Mb of non-contiguous DNA. Exon-amplification
      and cDNA selection methods were used in combination to extract the coding content
      from these cosmids, and to derive expressed sequences libraries. These libraries
      and the source cosmid library were arrayed at high density for hybridisation
      screening. A strategy was used which related data obtained by multiple
      hybridisations of clones originating from one library, screened against the other
      libraries. In this way, it was possible to integrate the information with the
      physical map and to compare the gene recovery rate of each technique. cDNAs and
      exons were grouped into bins delineated by EcoRI cosmid fragments, and a subset
      of 91 cDNAs and 29 exons have been sequenced. These sequences defined 79 non
      overlapping potential coding segments distributed in 24 transcriptional units,
      which were mapped along 21q. Northern blot analysis performed for a subset of
      cDNAs indicated the existence of a cognate transcript. Comparison to databases
      indicated three segments matching to known chromosome 21 genes: PFKL, COL6A1 and
      S100B and six segments matching to unmapped anonymous expressed sequence tags
      (ESTs). At the translated nucleotide level, strong homologies to known proteins
      were found with ATP-binding transporters of the ABC family and the dihydroorotase
      domain of pyrimidine synthetases. These data strongly suggest that bona fide
      partial genes have been isolated. Several of the newly isolated transcriptional
      units map to clinically important regions, in particular those involved in Down's
      syndrome, progressive myoclonus epilepsia and auto-immune polyglandular disease.
      The study presented here illustrates the complementarity of exon-amplification
      and cDNA selection techniques for generating a large resource of new expressed
      landmarks, which contribute to the construction of a chromosome 21 transcript
      map.

PMID- 7581367
TI  - Localization of 102 exons to a 2.5 Mb region involved in Down syndrome.
AB  - Exon amplification has been applied to a 2.5 Mb region of chromosome 21 that has
      been associated with some features of Down syndrome (DS). Identification of the
      majority of genes from this region will facilitate the correlation of the over
      expression of particular genes with specific phenotypes of DS. Over 100 gene
      fragments have been isolated from this 2.5 Mb segment. The exons have been
      characterized by sequence analysis, comparison with public databases and
      expansion to cDNA clones. Localization of the exons to chromosome 21 has been
      determined by hybridization to genomic Southern blots and to YAC and cosmid
      clones representing the region. This has resulted in a higher resolution physical
      map with a marker approximately every 25 kb. This integrated physical and
      transcript map will be valuable for fine mapping of DNA from individuals with
      partial aneuploidy of chromosome 21 as well as for assessing and ultimately
      generating a complete gene map of this segment of the genome.

PMID- 7581368
TI  - A widespread amino acid polymorphism at codon 905 of the glycogen-associated
      regulatory subunit of protein phosphatase-1 is associated with insulin resistance
      and hypersecretion of insulin.
AB  - The regulatory G-subunit of the glycogen-associated form of protein phosphatase 1
      (PP1) plays a crucial part in muscle tissue glycogen synthesis and breakdown. As
      impaired insulin stimulated glycogen synthesis in peripheral tissues is
      considered to be a pathogenic factor in subsets of non-insulin-dependent diabetes
      mellitus (NIDDM) and obesity, the G-subunit of PP1 should be viewed as a
      candidate gene for inherited insulin resistance. When applying heteroduplex
      formation analysis and nucleotide sequencing of PP1G-subunit cDNA from 30 insulin
      resistant white NIDDM patients two cases were identified as heterozygous carriers
      of an Asp905 --> Tyr substitution. The carrier prevalence of the PP1G-subunit
      variant was 18% in 150 healthy subjects and 13% in 313 NIDDM subjects (chi 2 =
      1.94, p = 0.16). Twenty-seven healthy subjects volunteered for a 4 h euglycaemic,
      hyperinsulinaemic clamp in combination with indirect calorimetry in order to
      elucidate the potential impact of the Tyr905 substitution on the whole body
      glucose metabolism. Interestingly, the Tyr905 variant was associated with altered
      routing of glucose: a decreased insulin stimulated non-oxidative glucose
      metabolism of peripheral tissues (glycogen synthesis) (p < 0.04) and an increased
      basal glucose oxidation rate (p < 0.04) when compared with wild type carriers. A
      population-based sample of 380 unrelated young healthy Caucasians was examined
      during a combined intravenous glucose and tolbutamide test to address whether the
      Asp905/Tyr905 polymorphism was associated with alterations in insulin secretion
      which might be secondary to the insulin resistance of skeletal muscle.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581369
TI  - Characterization of the 5' region of the Fanconi anaemia group C (FACC) gene.
AB  - Fanconi anaemia (FA) is an autosomal recessive disease characterised by
      progressive pancytopenia, chromosome instability and an increased risk of cancer.
      The Fanconi Anaemia Complementation Group C (FACC) gene is mutated in patients of
      complementation group C. Several different forms of FACC mRNA that share the same
      coding region have been isolated. At least two species result from the use of
      alternative exons at the 5' end and three result from the use of distinct
      polyadenylation signals. As a first step toward the characterization of this gene
      we have isolated the genomic clones corresponding to the 5' region, including a
      putative promoter and two alternate 5' exons. These exons, named -1 and -1a, were
      found to be separated by a small intron, with exon -1 located 5' to exon -1a.
      Further, these exons are flanked by consensus sequences of donor sites at the 5'
      ends of introns. An acceptor splice site was not evident 5' of exon -1a,
      suggesting that exon -1 is not spliced onto exon -1a. The sequences upstream of
      exons -1 and -1a have no obvious TATA or CAAT boxes but include CG-rich
      sequences. Functional analysis of the sequence upstream of the putative
      transcription start site of both alternative exons indicates that the region
      upstream exon -1 is sufficient to drive the expression of the luciferase reporter
      gene in CaCo-2 cells and that the transcriptional regulation of this gene is
      complex.

PMID- 7581371
TI  - A novel nonsense mutation in the PKD1 gene (C3817T) is associated with autosomal
      dominant polycystic kidney disease (ADPKD) in a large three-generation Italian
      family.
AB  - We have looked for disease-causing mutations in the PKD1 gene in 20 unrelated
      ADPKD probands from northern Italy, all members of families in which our previous
      studies had indicated linkage to PKD1. Using PCR with primer pairs located in the
      3' unique region of the gene and heteroduplex DNA analysis, we have detected
      novel aberrant bands in five affected individuals from the same family, which
      were absent in 13 other unaffected family members. Cloning and automated DNA
      sequencing revealed a C to T transition at nucleotide position 3817 of the
      published cDNA sequence, which created a premature stop codon. The mutation
      destroyed a MspA1I restriction site, and the abnormal restriction pattern was
      observed on genomic DNA from all the affected family members. RT-PCR and
      restriction analysis performed on peripheral white blood cell mRNA showed that in
      the affected members, both the mutant and the normal transcript are represented.
      This mutation was not found in the probands of the other families studied. To our
      knowledge, this is the first nonsense mutation described in the PKD1 gene.

PMID- 7581372
TI  - A transcribed human sequence related to the mouse HC1 and the human
      papillomavirus type 18 E5 genes is located at chromosome 7p13-14.
AB  - The papillomavirus E5 genes play an important role in the induction of
      proliferation of infected cells, and these HPV genomic regions are affected by
      the events leading to integration of genital HPVs. Two HPV18 E5-related,
      transcribed mouse sequences, HC1 and Q300, have recently been described. We
      searched for human equivalents to these sequences, and isolated a clone with a
      9.6 kb insert (633b) from a laryngeal carcinoma DNA library, that strongly cross
      hybridised with both the HPV18 E5 and HC1 sequences. Restriction and Southern
      blot analysis showed that 633b is a single copy sequence without rearrangements
      and viral sequences. The E5-related region is transcribed, producing a 1.9 kb RNA
      band detected in the poly(A)+ RNA from different cell lines tested. Sequence
      alignments showed a close similarity to the HC1 and HPV18 E5 sequences, as well
      as to Q300 and different viral and human growth factors, allowing to fit a
      putative phylogenetic tree. The corresponding human gene was named PE5L. It was
      mapped to the short arm of chromosome 7, at 7p13-14 as determined by in situ
      hybridisation. A genomic region with similarities to HPV E5 sequences may
      constitute an HPV-DNA integration target, which is often located near chromosomal
      breakpoints, oncogenes, etc. We conclude that PE5L belongs to an E5-like family
      of cellular sequences, and that it may constitute a target for HPV recombination.

PMID- 7581370
TI  - Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas
      syndrome.
AB  - The Pearson marrow-pancreas syndrome (MIM 557000) is a disorder involving the
      hematopoietic system and the exocrine pancreas in early infancy. We have
      previously shown that this disease results from a defect of oxidative
      phosphorylation associated with deletions of the mitochondrial DNA. We present
      here a series of 21 cases (including 15 unreported patients) with Pearson
      syndrome and describe mitochondrial DNA deletions as consistent features in this
      syndrome. Nine patients presented the same 4.9 kb deletion, while other patients
      presented different deletions ranging in size from 9 to 14 kb between tRNACyst
      and the D-loop. Direct repeats (4-13 bp) were consistently present in the wild
      type mtDNA at the boundaries of the deletions. Deletion-dimers, deletion
      multimers or duplications were observed in association with deletions.
      Duplications were identified both in patients who died of their Pearson syndrome
      and in the ones who survived and developed Kearns-Sayre syndrome, suggesting that
      no correlation could be made between the clinical severity and the type, size or
      location of the rearrangements.

PMID- 7581373
TI  - A yeast artificial chromosome contig from human chromosome 14q24 spanning the
      Alzheimer's disease locus AD3.
AB  - Familial Alzheimer's disease has been previously linked to three genetic loci on
      chromosomes 21, 19 and 14. The AD3 locus on chromosome 14 has not been cloned and
      the molecular defect in chromosome 14-linked AD3 families has yet to be
      identified. Genetic linkage analysis has placed the AD3 locus in band 14q24
      between the dinucleotide markers D14S61 and D14S289, a genetic distance of
      approximately 6.4 cM. We have constructed a yeast artificial chromosome (YAC)
      contig that covers the entire minimal region, encompassing all genetic markers
      that are non-recombinant for the disease in AD3-linked families. This contig,
      constructed by using a combination of YAC end sequence walking and sequence
      tagged site (STS) mapping, consists of 63 YACs from three different libraries.
      The AD3 contig contains 12 polymorphic dinucleotide repeat markers from D14S61 to
      D14S251, as well as an additional 43 non-polymorphic STSs. This contiguous
      physical map of the region will allow the physical distances between the markers
      to be determined, as well as providing a framework for the identification of
      candidate genes.

PMID- 7581374
TI  - Genetic and physical characterization of the early-onset Alzheimer's disease AD3
      locus on chromosome 14q24.3.
AB  - Genetic linkage studies have provided significant evidence that a major gene
      defect, AD3, for familial early-onset Alzheimer's disease (EOAD) is located at
      chromosome 14q24.3, between the short tandem repeat (STR) markers D14S52 and
      D14S53 defining a genetic size of 22.7 cM for the AD3 candidate region. We
      constructed a physical map of the AD3 region using yeast artificial chromosomes
      (YACs) selected from both the CEPH and megaCEPH YAC libraries using the AD3
      linked STR markers as well as new sequence-tagged sites (STSs) designed based on
      YAC terminal sequences. The YAC map is contiguous in the region between D14S258
      and D14S53, a region of 8.2 cM, and has an estimated physical size of 4-8 Mb. The
      YAC contig map was used as a framework to localize three known genes, a
      pseudogene and two brain expressed sequence tags (ESTs). Linkage analysis studies
      in two Belgian chromosome 14 EOAD families AD/A and AD/B, identified obligate
      recombinants in family AD/A with D14S289 and D14S61 reducing the genetic size of
      the candidate AD3 region substantially. The minimal AD3 candidate region measured
      6.4 cM on the genetic map and is contained within six overlapping megaCEPH YACs
      that covered a physical distance estimated between 2 and 6 Mb. These YACs as well
      as other YACs in the YAC contig map are valuable resources in gene cloning
      efforts or genomic sequencing experiments aiming at isolating the AD3 gene.

PMID- 7581375
TI  - Expression of the Huntington's disease (IT15) protein product in HD patients.
AB  - Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by
      expansion of a CAG repeat in the IT15 gene, leading to an expanded glutamine
      repeat in the HD protein. The mechanism by which the expanded repeat causes
      expression of the disease is not known, though there do not appear to be changes
      in the mRNA levels. We have conducted quantitative Western blot analyses of HD
      patients and controls. Expression of the IT15 protein is essentially equal in
      control and HD frontal cortex. In caudate from HD patients, IT15 protein is
      decreased in parallel with the decrease in a neuronal marker, suggesting that
      loss of IT15 protein is secondary to neuronal loss. In order to determine
      expression of the two alleles of the IT15 protein we used Western blots of 4%
      polyacrylamide gels. Both alleles of the IT15 protein were expressed at similar
      levels in HD lymphoblastoid cell lines and HD post-mortem hippocampus and
      cerebellum (regions relatively spared in HD), indicating that even very long CAG
      repeats can be translated into polyglutamine. In contrast, in cerebral cortex and
      caudate (regions severely affected in HD), in the longer expanded repeat cases
      the expanded allele of the IT15 protein was present at a significantly lower
      level (compared with the normal length allele), often with a smear of more slowly
      migrating reactivity above it. These data suggest the possibility of altered
      structure, abnormal processing or abnormality of protein-protein interactions
      involving the IT15 protein with the expanded glutamine repeat.

PMID- 7581376
TI  - Isolation of chromosome-specific genes by reciprocal probing of arrayed cDNA and
      cosmid libraries.
AB  - We have identified and mapped 61 novel and previously described chromosome 17 and
      X genes, using a human placental cDNA library. These genes were isolated using a
      gene identification and mapping strategy based on reciprocal probing of arrayed
      chromosome specific cosmid and cDNA libraries. This strategy scans gridded
      cosmids for nuclear genes and isolates the expressed sequence by a cosmid to cDNA
      filter hybridization. Inherent to this approach is the advantage of identifying
      the corresponding genomic cosmid clone of a particular cDNA. The genomic and cDNA
      reagents can be used for fluorescence in situ hybridization (FISH) and polymerase
      chain reaction (PCR) based mapping to resolve map positions of cDNAs belonging to
      gene families and those associated with multiple chromosomes. The downstream
      utility of reagents generated by the reciprocal probing methods is demonstrated
      in our studies.

PMID- 7581377
TI  - Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung
      disease.
AB  - Hirschsprung disease (HSCR) is a common congenital malformation (1 in 5,000 live
      births) due to the absence of autonomic ganglia in the terminal hindgut, and
      resulting in intestinal obstruction in neonates. Recently, a dominant gene for
      familial HSCR has been mapped to chromosome sub-band 10q11.2 and the disease has
      been ascribed to mutations in a tyrosine kinase receptor gene mapping to this
      region, the RET proto-oncogene. Studying the 20 exons of the RET gene by a
      combination of denaturating gradient gel electrophoresis and single strand
      conformation polymorphism in a large series of HSCR patients (45 sporadic cases
      and 35 familial forms), we found mutations of the RET gene in 50% of familial
      HSCR, regardless of the length of the aganglionic segment. The mean penetrance of
      the mutant allele in familial HSCR was significantly higher in males (72%) than
      in females (51%). Most interestingly, mutations at the RET locus accounted for at
      least 1/3 of sporadic HSCR in our series. These mutations were scattered along
      the length of the gene. Finally, among the mutations identified in sporadic cases
      (16/45), seven proved to be de novo mutations suggesting that new mutations at
      the RET locus significantly contribute to sporadic HSCR. Taken together, the low
      penetrance of the mutant gene, the lack of genotype-phenotype correlation, the
      sex-dependent effect of RET mutations and the variable clinical expression of the
      disease support the existence of one or more modifier genes in familial HSCR.

PMID- 7581378
TI  - Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common point
      mutation shared with Jackson-Weiss syndrome.
AB  - Dominant mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have
      been recently identified as causes of four phenotypically distinct
      craniosynostosis syndromes, including Crouzon, Jackson-Weiss, Pfeiffer, and Apert
      syndromes. These data suggest that the genetics of the craniosynostosis syndromes
      is more complex than would be expected from their simple autosomal-dominant
      inheritance pattern. Identical mutations in the FGFR2 gene have been reported to
      cause both Pfeiffer and Crouzon syndrome phenotypes. We now report the finding of
      a mutation in exon IIIc of the FGFR2 gene in a kindred affected with Crouzon
      syndrome (C1043 to G; Ala344Gly) that is identical to the mutation previously
      associated with Jackson-Weiss syndrome. We also report finding in a Crouzon
      kindred a mutation in the 3' end of exon IIIu (formerly referred to as exon 5,
      exon 7, or exon U) (A878 to C; Gln289Pro) which encodes the amino terminal
      portion of the Ig-like III domain of the FGFR2 protein. This exon is common to
      both the FGFR2 and the KGFR spliceoforms of the FGFR2 gene, unlike all previously
      reported Crouzon mutations, which have been found only in the FGFR2 spliceoform.
      These findings reveal further unexpected complexity in the molecular genetics of
      these craniosynostosis syndromes. The data implies that second-site mutations in
      FGFR2 itself (outside of exon IIIc) or in other genes may determine specific
      aspects of the phenotypes of craniosynostosis syndromes.

PMID- 7581379
TI  - Autosomal recessive lamellar ichthyosis: identification of a new mutation in
      transglutaminase 1 and evidence for genetic heterogeneity.
AB  - Autosomal recessive lamellar ichthyosis (ARLI) belongs to the group of congenital
      disorders of cornification. It is characterized by a severe and generalized
      ichthyosis, and other variable cutaneous signs. The human transglutaminase 1
      (TGM1) gene was recently found to be the disease-causing gene. Linkage analysis
      in 23 families (of which 13 were consanguineous) showed that for 10 of them, the
      disease was linked to the TGM1 gene. A new deleterious mutation introducing a
      stop codon in the TGM1 reading frame was found. Nevertheless, for the 13 other
      ARLI families, TGM1 was found to be unlinked to the disease. The present data
      show that ARLI is genetically heterogeneous and confirm that TGM1 is one of the
      responsible genes.

PMID- 7581380
TI  - Myotonia levior is a chloride channel disorder.
AB  - The group of dominant non-dystrophic myotonias, comprising disorders
      characterized by clinically similar forms of myogenic muscle stiffness, is
      genetically inhomogeneous. Dominant myotonia congenita (Thomsen's disease) is
      linked to CLCN1, the gene encoding the major muscle chloride channel, localized
      on chromosome 7q35. In contrast, dominant myotonias sensitive to potassium are
      caused by point mutations in SCN4A on chromosome 17q, the gene for the alpha
      subunit of the adult skeletal muscle sodium channel. No linkage or molecular
      genetic data are as yet available on 'myotonia levior' characterized by milder
      symptoms and later onset of myotonia than in Thomsen's disease, and absence of
      muscle hypertrophy. We report a CLCN1 Gln-552-Arg substitution for a family with
      dominant inheritance previously diagnosed to have myotonia levior. Thus, this
      disorder appears as a variant of Thomsen's disease due to mutations leading to
      low clinical expressivity. In addition, we report a novel Ile-290-Met CLCN1
      mutation for a typical Thomsen pedigree. In another family previously diagnosed
      as having Thomsen's disease, we unexpectedly found a CLCN1 14 bp deletion known
      to cause recessive myotonia, and a rare Trp-118-Gly polymorphism.

PMID- 7581381
TI  - Inactivation of Apoe and Apoc1 by two consecutive rounds of gene targeting:
      effects on mRNA expression levels of gene cluster members.
AB  - The genes encoding apolipoprotein (apo) E and apoC1 are, together with the gene
      for apoC2, located in a conserved gene cluster on human chromosome 19q12-13.2 and
      mouse chromosome 7. Although the significance of apoE as a ligand for receptor
      mediated uptake of lipoprotein remnant particles is undisputed, the in vivo
      function of apoC1 and the possible interaction between apoE and apoC1 in the
      modulation of plasma cholesterol and triglyceride levels is far from understood.
      Our strategy to unravel the metabolic relationship between apoE and apoC1 in vivo
      is to first generate mice deficient in both apolipoproteins, enabling future
      production of transgenic mice with variable ratios of normal and mutant apoE and
      apoC1 on a null background. Here we report the creation and characterization of
      mice deficient in both apoE and apoC1. As these genes are tightly genetically
      linked, double-deficient mice were obtained by two consecutive rounds of gene
      targeting in mouse embryonic stem cells. Surprisingly, double inactivation of the
      Apoe and Apoc1 gene loci as well as single inactivations at either one of these
      loci were found to affect also the RNA expression levels of the other gene
      members in the Apoe-c1-c2 cluster. This indicates that targeted insertions are
      not necessarily neutral for the expression of nearby gene members in a given gene
      cluster. Homozygous Apoe-c1 knockout mice are hypercholesterolemic, with serum
      cholesterol levels of 12.5 +/- 4.3 mM compared with 2.9 +/- 0.5 mM in control
      mice, resembling mice solely deficient in apoE.

PMID- 7581382
TI  - Friedreich's ataxia: a defect in signal transduction?
AB  - We have previously assigned the mutation causing Friedreich's ataxia (FRDA) to
      9q13 by genetic linkage and fluorescent in situ hybridization analysis, and
      identified recombination events which position the gene centromeric to D9S5. We
      report here the extension of a yeast artificial chromosome contig to span the 860
      kb interval immediately proximal to this marker, which includes the D9S886 and
      D9S887/888 loci reported to flank the FRDA locus, and the construction of a high
      resolution cosmid contig initiated from the D9S888 locus. Exon trapping and cDNA
      library screening strategies have resulted in the isolation of a candidate gene
      which traverses the centromeric boundary of the FRDA critical region. The gene
      spans a genomic interval greater than 220 kb with at least two of the coding
      exons located proximal to the D9S887/888 loci. Expression is complex, with
      multiple transcripts detected in a variety of tissues and evidence of alternative
      splicing and developmental control. The predicted amino acid sequence for the 2.7
      kb transcript reported here shows a marked homology to the deduced amino acid
      sequence of the Saccharomyces cerevisiae MSS4 protein, proposed to function
      within the phosphoinositide cycle, suggesting a potential role for the human
      homologue in signal transduction. Whilst no evidence for mutation has been
      detected in this transcript, the sequence represents only one of the shorter
      alternatively spliced species identified by Northern analysis and direct
      sequencing. This gene remains a strong candidate for FRDA.

PMID- 7581383
TI  - Maternally inherited hearing loss, ataxia and myoclonus associated with a novel
      point mutation in mitochondrial tRNASer(UCN) gene.
AB  - We report on a new maternally-inherited syndrome characterized by a combination
      of sensorineural hearing loss, ataxia and myoclonus in a large kindred from
      Sicily. Hearing loss was the most widespread and sometimes the only symptom found
      in family members. Sequence analysis of the mitochondrial DNA regions
      encompassing the tRNA genes revealed the presence of a heteroplasmic insertion at
      nucleotide position 7472. The insertion adds a seventh cytosine to a six-cytosine
      run that is part of the mitochondrial tRNASer(UCN) gene. Conformational analysis
      showed that this mutation is likely to alter the structure of the T psi C loop in
      the tRNASer(UCN) clover leaf secondary structure. Moreover, the degree of
      heteroplasmy in blood and muscle was correlated with the clinical phenotype, and
      homoplasmic mutant hybrids showed decreased complex I activity, low oxygen
      consumption and high lactic acid output, indicating faulty oxidative
      phosphorylation. Finally, mutation was absent in 381 unrelated maternal lineages,
      suggesting specific segregation with the disease. We propose that the C7472
      insertion-mutation is pathogenic, and etiologically related to hearing loss and
      other symptoms that define a novel maternally-inherited clinical entity.

PMID- 7581384
TI  - A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell
      hypoplasia.
AB  - Leydig cell hypoplasia (LCH) is a form of male pseudohermaphroditism in which
      Leydig cell differentiation and testosterone production are impaired. This report
      describes the first case of a nonsense mutation (A1635C) in exon 11 of the human
      luteinizing hormone receptor (hLHR) gene in two sisters with LCH. This mutation
      causes loss of function of the receptor by introducing a stop codon at residue
      545 in transmembrane helix 5 of the hLHR. Surface expression of the truncated
      hLHR (hLHR-t545) in human embryonic kidney cells stably transfected with cDNA
      encoding hLHR-t545 was diminished compared to the wild-type hLHR and hCG-induced
      cAMP accumulation was impaired. These results establish that single base
      mutations in exon 11 of the hLHR gene can produce inactivation as well as
      activation of the hLHR. Furthermore, they demonstrate that functional domains
      between transmembrane helix 5 and the C-terminal cytoplasmic tail of the hLHR are
      required for normal cell surface expression of the receptor and signal
      transduction.

PMID- 7581385
TI  - Linkage of autosomal dominant iris hypoplasia to the region of the Rieger
      syndrome locus (4q25).
AB  - Iris hypoplasia is an autosomal dominant disorder which is frequently associated
      with glaucoma. This glaucoma is usually resistant to medical therapy and can lead
      to blindness. A large family of Scandinavian descent with a five generation
      history of iris hypoplasia was studied. Fifteen individuals were found to have
      iris hypoplasia, nine of whom had associated glaucoma. In an attempt to identify
      the chromosomal location of the disease-causing gene, this family was genotyped
      with short tandem repeat polymorphisms (STRPs) known to map to loci previously
      associated with glaucoma. The juvenile glaucoma locus at 1q25 and a congenital
      glaucoma locus on 6p were both statistically excluded. However, significant
      linkage was demonstrated at the Rieger syndrome locus at 4q25. The highest
      observed LOD score was 3.70 (theta = 0) and was obtained with marker D4S1616.
      Three recombination events were observed in affected individuals that together
      demonstrate that the disease-causing gene lies between markers ACT3E03 and
      D4S1611, an interval of approximately 7 cM. These results suggest that autosomal
      dominant iris hypoplasia and Rieger syndrome are allelic.

PMID- 7581386
TI  - Localization of autosomal dominant cerebellar ataxia associated with retinal
      degeneration and anticipation to chromosome 3p12-p21.1.
AB  - We present linkage analysis on a large Swedish five-generation family of 15
      affected individuals with autosomal dominant cerebellar ataxia (ADCA) associated
      with retinal degeneration and anticipation. Common clinical signs in this family
      include ataxia, dysarthria and severely impaired vision with the phenotype ADCA
      type II. Different subtypes of ADCA have proven difficult to classify clinically
      due to extensive phenotypic variability within and between families. Genetic
      analysis of a number of ADCA type I families shows that heterogeneity exists also
      genetically. During the last few years several types of ADCA type I have been
      localized and to date six genetically distinct forms have been identified
      including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph disease (MJD) (14q),
      SCA4 (16q), and finally SCA5 (11). We performed a genome-wide search of the
      Swedish ADCA type II family using a total of 270 microsatellite markers. Positive
      lod scores were obtained with a number of microsatellite markers located on
      chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod
      score of 4.53 achieved with the marker D3S1600. The ADCA type II gene could be
      restricted to a region of 32 cM by the markers D3S1547 and D3S1274.

PMID- 7581387
TI  - A gene for Leber's congenital amaurosis maps to chromosome 17p.
AB  - Leber's congenital amaurosis (LCA) is an autosomal recessive disease responsible
      for congenital blindness. It is the most early and severe form of inherited
      retinopathy and accounts for 5% of all inherited retinal dystrophies. Here we
      report the first mapping of a gene for LCA to the distal short arm of chromosome
      17 by linkage analysis in 15 multiplex families (Zmax = 5.14 at theta = 0.15 for
      probe AFM070xg5 at the D17S1353 locus). When our sample was split into two groups
      according to the ethnic origin of the patients we were able to confirm the
      presence of a gene for LCA on chromosome 17p by both homozygosity mapping and
      linkage analysis in five families of Maghrebian origin (LCA1, Zmax = 7.21 at
      theta = 0.01 at the D17S1353 locus), while negative results were found in 10
      families of French ancestry. Haplotype analyses supported the placement of LCA1
      between loci D17S796 and D17S786 (maximum likelihood estimate for location of the
      disease gene over the D17S1353 locus). The genetic heterogeneity of LCA will
      complicate the prenatal detection of this frequent cause of congenital blindness.

PMID- 7581388
TI  - Localization of the syndactyly type II (synpolydactyly) locus to 2q31 region and
      identification of tight linkage to HOXD8 intragenic marker.
AB  - Syndactyly type II (SynPolyDactyly; SPD) is an autosomal dominant condition with
      incomplete penetrance and variable expressivity. Sixty-two meioses from a kindred
      with 425 individuals were used to map the SPD locus to 2q31 region, approximately
      1.7 cM (Lod score = 12.96) centromeric to HOXD8 intragenic marker. Other homeobox
      containing genes in this region have previously been ordered as cen-DLX1/DLX2
      EVX2-(5' --> HOXD13..HOXD8.HOXD1 --> 3')-tel')-tel. A single recombinant with
      HOXD8 excluded the most 3' end of HOXD cluster as a candidate site for SPD, but a
      mutation in the 5' end of HOXD cluster, especially in HOXD13, EVX2 or DLX2/DLX1,
      may still be responsible for this phenotype. An updated order of D2S142-D2S111
      (D2S335/D2S333)-D2S326-D2 S1238-SPD- (HOXD8/D2S1244)-(D2S300/D2S138)-D2S148-
      D2S324- D2S1384-D2S434 [sequence:see text] was deduced from meiotic recombination
      events.

PMID- 7581389
TI  - An eighth locus for autosomal dominant retinitis pigmentosa is linked to
      chromosome 17q.
AB  - Retinitis pigmentosa is one of the most common causes of severe visual handicap
      in middle to late life. Prior to this report, seven loci had previously been
      mapped for the autosomal dominant form of this disorder (adRP). We now report the
      identification of a novel adRP locus on chromosome 17q. To map the new locus, we
      performed linkage analysis with microsatellite markers in a large South African
      kindred. After exclusion of 13 RP candidate gene loci (including rhodopsin and
      peripherin-RDS), we obtained significant positive lod scores at zero
      recombination fraction (theta = 0) for D17S808 (Z = 4.63) and D17S807 (Z = 5.69).
      Multipoint analysis gave a maximum lod score of 8.28 between these two markers.
      From haplotype analysis, the disease locus lies in the interval between markers
      D17S809 and D17S942. Three candidate genes for retinal dystrophies map to this
      chromosomal region and these genes are currently being investigated for possible
      involvement with adRP in this family.

PMID- 7581390
TI  - Recurrent nasal polyps as a monosymptomatic form of cystic fibrosis associated
      with a novel in-frame deletion (591del18) in the CFTR gene.

PMID- 7581391
TI  - Molecular analysis of four males with mental retardation and deletions of Xq21
      places the putative MR region in Xq21.1 between DXS233 and CHM.

PMID- 7581393
TI  - A de novo frame-shift mutation in the tuberin gene.

PMID- 7581392
TI  - Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked
      deafness, DFN3.

PMID- 7581394
TI  - Mutational analysis of patients with X-linked adrenoleukodystrophy.
AB  - Adrenoleukodystrophy (ALD) is an X-linked neurodegenerative disorder
      characterized by elevated very long chain fatty acid (VLCFA) levels, reduced
      activity of peroxisomal VLCFA-CoA ligase, and variable phenotypic expression. A
      putative gene for ALD was recently identified and surprisingly encodes a protein
      (ALDP) that belongs to a family of transmembrane transporters regulated or
      activated by ATP (the ABC proteins). We have examined genomic DNA from ALD
      probands for mutations in the putative ALD gene. We detected large deletions of
      the carboxyl-terminal portion of the gene in 4 of 112 probands. Twenty-five of
      the ALD probands whose ALD genes appeared normal by Southern blot analysis were
      surveyed for mutations by Single Strand Conformation Polymorphism (SSCP)
      procedures and DNA sequence analysis. SSCP variants were detected in 22 probands
      and none in 60 X-chromosomes from normal individuals. Mutations were detected in
      all of the ALD probands. The mutations were distributed throughout the gene and
      did not correlate with phenotype. Approximately half were non-recurrent missense
      mutations of which 64% occurred in CpG dinucleotides. There was a cluster of
      frameshift mutations in a small region of exon 5, including an identical AG
      deletion in 7 unrelated probands. These data strongly support the supposition
      that mutations in the putative ALD gene result in ALD.

PMID- 7581395
TI  - Aberrant splicing of the type III procollagen mRNA leads to intracellular
      degradation of the protein in a patient with Ehlers-Danlos type IV.
AB  - Ehlers-Danlos syndrome type IV (EDS IV) is an autosomal dominant disorder
      characterized by fragile skin, blood vessels, and internal organs and associated
      with decreased production, secretion, or thermal stability of type III
      procollagen. Mutations in the gene for type III procollagen have been identified
      in patients exhibiting decreased secretion or thermal stability of the protein,
      but no defect has been elucidated to explain the decreased production of type III
      procollagen in some patients with EDS IV. We report on a patient with a moderate
      case of EDS IV who produced decreased amounts of type III procollagen despite
      normal levels of translatable type III procollagen mRNA. S1 nuclease analysis of
      the type III procollagen mRNA indicated a defect in the region encoding exon 27.
      Sequence analysis of cDNA clones and genomic fragments generated by polymerase
      chain reaction amplification revealed that sequences encoded by exon 27 were
      absent from 3 out of 5 cDNA clones and that a G at the +5 position of the splice
      donor site in intron 27 was changed to an A in one allele of the patient's type
      III procollagen gene. Using a cDNA-genomic DNA hybrid probe in S1 nuclease
      analysis, fragments consistent with mRNA species containing and lacking exon 27
      were detected in a 1:1 ratio. Pulse label and chase experiments in the presence
      or absence of brefeldin A indicated that most of the type III procollagen
      molecules synthesized by the patient's fibroblasts were not secreted into the
      medium but were degraded in the endoplasmic reticulum-Golgi compartment by a
      nonlysosomal mechanism.

PMID- 7581396
TI  - Protein truncation test: analysis of two novel point mutations at the carboxy
      terminus of the human dystrophin gene associated with mental retardation.
AB  - Approximately one-third of the mutations responsible for Duchenne muscular
      dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene.
      Methods for intensive mutation screening have recently been applied to this
      immense gene, which resulted in the identification of a number of point mutations
      in DMD patients, mostly translation-terminating mutations. A number of data
      raised the possibility that the C-terminal region of dystrophin might be involved
      in some cases of mental retardation associated with DMD. Using single-strand
      conformation analysis of products amplified by polymerase chain reaction (PCR
      SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20
      unrelated patients with DMD or BMD, we detected two novel point mutations in two
      mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5'
      splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should
      result in a premature translation termination of dystrophin. The possible effects
      on the reading frame were analyzed by the study of reverse transcripts amplified
      from peripheral blood lymphocytes mRNA and by the protein truncation test.

PMID- 7581397
TI  - Mucopolysaccharidosis type II (Hunter disease): identification and
      characterization of eight point mutations in the iduronate-2-sulfatase gene in
      Japanese patients.
AB  - Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder
      caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical
      phenotypes of this disease have been described. To identify mutations in
      individual patients and to examine possible correlations between mutations and
      clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese
      patients with different clinical phenotypes. Five missense mutations, S333L
      (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and
      three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild),
      were identified by the RT-PCR method. Transient expression in the enzyme
      deficient fibroblasts revealed that all five missense mutant enzymes were
      synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes
      were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD),
      although stable mature enzymes (45-56 kD) were not detected by Western blot
      analysis. Furthermore, expression of the eight mutant cDNAs resulted in severe
      reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal
      cDNA.

PMID- 7581398
TI  - Simultaneous analysis of mutant and normal alleles for multiple cystic fibrosis
      mutations by the ligase chain reaction.
AB  - The ligase chain reaction (LCR) involves repetitive cycles of ligation of two
      adjacent pairs of oligonucleotides to form longer ligated products in a template
      dependent manner. This study demonstrates the application of LCR for analysis of
      multiple small mutations. We adapted the technology for the simultaneous
      determination of the normal and mutant alleles in a competition format, as well
      as multiple mutations in a multiplex format. For these purposes, we used
      mutations causing cystic fibrosis, namely the delta F508, W1282X, and G551D
      mutations. Blunt ligation was compared to a strategy with a single base gap on
      one or both strands to be filled by thermostable polymerase prior to ligation.
      Blunt or gap strategies worked well for detection of the delta F508 mutation.
      Detection of the W1282X mutation worked well with a blunt strategy when high K+
      concentration (180-220 mM) was used to reduce template-independent ligation. For
      reliable detection of the G551D mutation, we used mismatches in the
      oligonucleotides 2-5 bp away from the ligation site and hot start of the reaction
      to achieve allele specificity. Excellent discrimination of mutations was achieved
      using competitive LCR with six oligonucleotides (two common on one side of the
      mutation plus two wild type and two mutant on the opposite side with the mutation
      site at the end adjacent to the common oligonucleotides) and with multiplex
      competitive LCR using 12 oligonucleotides to detect both alleles for two
      mutations in a single tube.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581399
TI  - Human androgen insensitivity due to point mutations encoding amino acid
      substitutions in the androgen receptor steroid-binding domain.
AB  - Mutations of the human androgen receptor gene were identified in five subjects
      from four families with androgen insensitivity syndrome. Individual exons of the
      androgen receptor gene were amplified by the polymerase chain reaction from
      genomic DNA and screened for sequence-dependent differences in their melting
      characteristics by denaturing gradient gel electrophoresis. DNA fragments from
      exons with altered mobility were sequenced. Four different single nucleotide base
      substitutions were found within exons 5, 6, and 7 encoding the steroid-binding
      domain of the androgen receptor. In one subject with ambiguous genitalia, amino
      acid residue 763 was changed from tyrosine to cysteine (TAC-->TGC; Y763C). Four
      subjects, including two siblings, had complete androgen insensitivity. In one
      subject, residue 779 was changed from arginine to tryptophan (CGC-->TGG; R779W),
      another subject (M807V) had a substitution of valine (GTG) for methionine (ATG)
      residue at position 807, and the two siblings (R855C) had a mutation in residue
      855 changing arginine (CGC) to cysteine (TGC). Binding of the synthetic androgen
      ligand, methyltrienolone (R1881), by the mutant receptor Y763C was decreased by
      54% compared to the normal receptor. Transcriptional activation of a mouse
      mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter gene by
      AR mutant Y763C was negligible at 0.1 nM R1881 and only 55% at 10 nM R1881 when
      compared to the maximal response with the normal AR, as assessed by CAT activity.
      Mutant M807V retained only 22% of normal R1881 binding and mutant R855C was
      unable to bind the steroid. In accordance with the steroid binding,
      transcriptional activation of MMTV-CAT by M807V rose to only 26% of control in
      the presence of 10 nM R1881, a concentration at which R855C remained functionally
      inactive. In summary, missense mutations within the exons of the androgen
      receptor gene encoding the steroid-binding domain of the receptor are common
      causes of both partial and complete forms of androgen insensitivity syndrome.

PMID- 7581401
TI  - Identification of seven novel mutations associated with metachromatic
      leukodystrophy.

PMID- 7581400
TI  - Allele-specific competitive blocker PCR: a one-step method with applicability to
      pool screening.
AB  - We have developed a novel one-step pool screening PCR procedure which is based on
      the principles of amplification refractory mutation system (ARMS) and competitive
      oligonuleotide priming (COP) PCR. In addition to the usual primers, this approach
      uses two allele-specific competitive oligonucleotides, one of which is 3'-end
      labeled with a dideoxynucleotide and blocks amplification of the wild-type
      allele. An allele-specific product is generated only in the presence of the
      mutation. The introduction of an allele-specific competitive blocker
      oligonucleotide improves the specificity and robustness of ARMS-PCR. Further its
      sensitivity is dramatically increased, which allows detection of one mutant
      allele in a large excess of wild-type-bearing genomic DNA by electrophoresis in
      an ethidium bromide-stained agarose gel (up to 1 in 10(4) alleles). This makes
      the method ideal for nonradioactive pool screening. The successful application of
      the method has been demonstrated for four different point mutations, two in the
      apolipoprotein B gene (R3500Q, R3531C) which result in familial defective
      apolipoprotein B-100, one in the CFTR gene (R1162X), and one in the gene for
      lipoprotein lipase (G188E).

PMID- 7581402
TI  - High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish
      homocystinuria patients.

PMID- 7581403
TI  - A de novo duplication in the low density lipoprotein receptor gene.

PMID- 7581404
TI  - A nonsense mutation in two German patients with fucosidosis.

PMID- 7581406
TI  - Identification of two novel mutations in the cystic fibrosis gene: 1898+3A-->C
      and 2711delT.

PMID- 7581405
TI  - New point mutation (R301X) of the alpha-galactosidase A gene causing Fabry
      disease.

PMID- 7581408
TI  - Mutation analysis of phenylketonuria in south and central Portugal: prevalence of
      V388M mutation.

PMID- 7581407
TI  - Novel missense mutation in the first transmembrane segment of the CFTR gene
      (Q98R) identified in a male adult.

PMID- 7581411
TI  - Mutations in the estrogen receptor gene.
AB  - Somatically generated mutations in the estrogen receptor (ER) have been found at
      the mRNA/cDNA level in human breast cancer biopsies and in established breast
      cancer cell lines. Aberrantly spliced ER mRNA causes the appearance of truncated
      or internally deleted ER protein forms. Studies on the functional activity of the
      ER variants in expression systems have revealed dominant-positive receptors that
      are transcriptionally active in the absence of estrogen, and dominant-negative
      receptors that are themselves transcriptionally inactive but that prevent the
      action of the normal receptor. The ER variants are believed to confer resistance
      to endocrine therapy in breast cancer patients. Abnormally spliced forms of ER,
      similar to those in breast cancer, have been reported in human meningiomas.

PMID- 7581410
TI  - Identification of a novel Ala797Thr mutation in exon 21 of the beta-myosin heavy
      chain gene in hypertrophic cardiomyopathy.

PMID- 7581412
TI  - Controlled study of eating concerns and psychopathological traits in relatives of
      eating-disordered probands: do familial traits exist?
AB  - To examine the extent to which first-degree relatives of eating-disordered (ED)
      probands endorse maladaptive eating attitudes and personality/affective traits,
      we compared self-reported eating concerns (Restraint, Emotional Eating, Body
      Dissatisfaction, and maladaptive eating attitudes) and psychopathological traits
      (Affective Instability, Anxiousness, Compulsivity, and Narcissism) across groups
      of restricter (n = 19), binger (n = 56), psychiatric control (PC, n = 38), normal
      dieter (ND, n = 29), and nondieter control (NC, n = 28) probands, and then across
      participating nuclear family members. Results among probands were as anticipated:
      ED probands showed expected elevations in both areas, and predicted
      restricter/binger differences were obtained. However, corresponding differences
      were not obtained on measures of mothers', fathers', or siblings' eating concerns
      and traits. Our findings corroborate the notion that EDs represent a convergence
      of eating, affective, and personality disturbances, but not that such a
      clustering of features exists as a familial trait. We discuss normal trait and
      attitudinal variations observed in ED probands' relatives in light of findings
      showing EDs and other psychiatric syndromes to aggregate within families.

PMID- 7581409
TI  - Two new mutations, Q473X and N487S, in a Caucasian patient with
      mucopolysaccharidosis IVA (Morquio disease).

PMID- 7581414
TI  - Bulimia nervosa: 5-year social outcome and relationship to eating pathology.
AB  - From an original sample of 50 patients, 32 female patients with bulimia nervosa
      were followed up for a minimum length of 5 years. Standardized interviews were
      employed to assess eating attitudes and behavior as well as social status both at
      entry and at completion of the follow-up period. All participants completed the
      Social Problem Questionnaire at follow-up. Social outcome was found to parallel
      eating disorder outcome. Being in a satisfactory stable relationship was
      associated with good eating disorder outcome. Being in a stable relationship was
      not related to eating disorder outcome. Good outcome was also associated with
      higher occupational social class, and having a fulfilling social life and job.

PMID- 7581413
TI  - General population-based epidemiological study of eating disorders in Norway.
AB  - In a questionnaire-based study of eating disorders in a representative sample of
      the general female population of Norway, the lifetime prevalence of eating
      disorders was 8.7% with a point prevalence of 3.8%. The lifetime prevalence of
      binge eating disorder (BED) was 3.2%, bulimia nervosa (BN) 1.6%, and anorexia
      nervosa (AN) 0.4%. Eating disorders not otherwise specified (EDNOS) had a
      lifetime prevalence of 3.0%. Point prevalence of BED was 1.5%, BN 0.7%, AN 0.3%,
      and EDNOS 1.3%.

PMID- 7581415
TI  - An age-matched comparison of subjects with binge eating disorder and bulimia
      nervosa.
AB  - The purpose of this study was to compare data from a group of obese subjects with
      binge eating disorder (BED) with data from a group of normal weight bulimia
      nervosa (BN) subjects. Subjects were compared using the Eating Disorder
      Questionnaire (EDQ), the Eating Disorder Inventory (EDI), the Personality
      Disorders Questionnaire for DSM-III-R (PDQ-R), the Hamilton Anxiety and
      Depression Rating Scales, and the Beck Depression Inventory. A group of 35 age
      matched subjects were selected retrospectively from treatment study subjects. The
      EDQ findings indicated that members of the BN group desired a lower body mass
      index, were more afraid of becoming fat, and more uncomfortable with their binge
      eating behavior than the BED group members. The BED subjects had a younger age of
      onset of binge eating behavior (14.3) than the BN subjects (19.8), even though
      both groups started dieting at a similar age (BED = 15.0, BN = 16.2). The EDI
      results showed BN subjects had more eating and weight-related pathology, with
      significantly higher scores on five of the eight subscales. On the PDQ-R more BN
      subjects endorsed Axis II impairment (BN = 69%, BED = 40%). While demonstrating
      greater eating pathology in the BN group, this study also found significant
      pathology and distress in BED subjects.

PMID- 7581417
TI  - Feelings and fantasy in eating disorders: a factor analysis of the Toronto
      Alexithymia Scale.
AB  - The aim of the study was to examine the factor structure of alexithymia in
      patients with eating disorders and to compare scores on these factors with a non
      eating disordered population. The Toronto Alexithymia Scale (TAS) was given to
      patients with restricting anorexia nervosa (AN/R, n = 29), bulimia nervosa (BN, n
      = 83), anorexia with a subtype bulimia (AN/BN, n = 15), and 79 female students.
      Factors were extracted using a principal-components factor analysis. Four factors
      were found--inability to Identify Feelings, Paucity of Fantasy, Noncommunication
      of Feelings, and Concrete Thinking. All three eating disorder groups were less
      able to identify their feelings than the comparison group and AN/R patients had a
      more diminished fantasy life than BN patients and students. Groups did not differ
      significantly on concrete thinking but there was a trend towards significance on
      noncommunication of feelings, with patient groups expressing their feelings less
      than comparison subjects. Differences between patient groups on factors of the
      TAS suggest that scores are not simply a result of psychopathology in general.
      Approaches which promote the identification and expression of feelings may be
      particularly useful in the treatment of eating disorders.

PMID- 7581416
TI  - Abnormal eating and dissociative experiences: a further study of college women.
AB  - A total of 241 female college students completed the Eating Disorder Inventory
      (EDI) and a battery of other scales measuring tendencies toward psychopathology.
      Both abnormal eating and ego dysfunction were most strongly associated with
      depression; lower correlations were obtained with dissociation, fears, obsessions
      and compulsions, perceptual aberration, and magical ideation. Panic disorder was
      associated with abnormal eating but not ego dysfunction. There appears to be no
      specific association between eating disorder and dissociation.

PMID- 7581418
TI  - Body image and steroid use in male bodybuilders.
AB  - This study was designed to examine the association between body image and eating
      related attitudes among male bodybuilders in relation to two athletic comparison
      groups, runners and martial artists. It was also of interest to examine whether
      steroid use may be associated with body image disturbances in athletes. The
      volunteer sample of 139 male athletes recruited from fitness centers comprised 43
      bodybuilders, 48 runners, and 48 martial artists (tae kwon do practitioners).
      Standardized measures of body dissatisfaction, drive for thinness, drive for
      bulk, bulimia, self-esteem, depression, maturity fears, and perfectionism as well
      as questionnaires designed to measure attitudes toward steroids, and rates of
      steroid use were administered in a manner that encouraged disclosure.
      Bodybuilders reported significantly greater body dissatisfaction, with a high
      drive for bulk, high drive for thinness, and increased bulimic tendencies than
      either of the other athletic groups. In addition bodybuilders reported
      significant elevations on measures of perfectionism, ineffectiveness, and lower
      self-esteem. They also reported the greatest use of anabolic steroids and most
      liberal attitudes towards using steroids. Steroid users reported that the most
      significant reason for using steroids was to improve looks. Steroid users
      reported an elevated drive to put on muscle mass in the form of bulk, greater
      maturity fears, and enhanced bulimic tendencies than nonusers. The results
      suggest that male bodybuilders are at risk for body image disturbance and the
      associated psychological characteristics that have been commonly reported among
      eating disorder patients. These psychological characteristics also appear to
      predict steroid use in this group of males.

PMID- 7581419
TI  - Binge eating disorder in a community-based sample of successful and unsuccessful
      dieters.
AB  - This study examined binge eating and weight cycling in a community-based sample
      of successful (46 women, 44 men) and unsuccessful (29 women, 25 men) dieters.
      Successful dieters had lost at least 15% of body weight, kept the weight off for
      at least 1 year, and regained no more than 10 lb (average weight loss = 48 lb).
      Subjects completed a written questionnaire and were interviewed by phone several
      weeks later. Unsuccessful dieters were more obese when starting on a diet
      (average body mass index = 35.6 compared to 32.1) and were much more likely to
      have lost and regained 20 lb. Six-month prevalence of binge eating disorder (BED)
      was 19% for unsuccessful dieters and 6% for successful dieters; lifetime
      prevalence was 15% and 13%, respectively. Unsuccessful dieters were two to three
      times more likely to perceive a lack of control during an episode of overeating,
      to be disgusted with themselves for overeating, and to eat alone because they
      were embarrassed. Encouraging dieters to set realistic goals, identify potential
      relapse situations, and interpret lapses may help them succeed.

PMID- 7581420
TI  - Ethnic/racial and socioeconomic differences in dieting behaviors and body image
      perceptions in adolescents.
AB  - This study examined differences in perceptions of body weight, dieting, unhealthy
      eating behaviors, and weight control methods among adolescent males and females
      of various racial/ethnic and socioeconomic (SES) subgroups. Data were derived
      from a comprehensive health survey administered to 36,320 students in grades 7
      through 12 in Minnesota. Differences among ethnic/racial and SES groups were
      assessed using multivariate logistic regression controlling for grade and body
      mass index (BMI). Results showed that unhealthy weight control behaviors are not
      confined to upper SES white females. Compared to white females, Hispanic females
      reported greater use of diuretics; Asians reported more binge eating; and blacks
      reported higher rates of vomiting. Black and American Indian females were more
      likely to be satisfied with their body. Among males and females, higher SES was
      associated with greater weight satisfaction and lower rates of pathological
      weight control behaviors. Findings from this study suggest that future research
      should focus on the validity of self-reports of dieting and weight control
      behaviors in different ethnic subgroups.

PMID- 7581421
TI  - Sociocultural influences on eating attitudes and behaviors, body image, and
      psychological functioning: a comparison of African-American, Asian-American, and
      Caucasian college women.
AB  - Eating attitudes and behaviors, body image, and psychological functioning were
      evaluated in 98 female college students: 36 African-Americans, 34 Asian
      Americans, and 28 Caucasians. African-Americans had significantly higher body
      mass index than either Asian-American or Caucasians. In contrast, Caucasians
      reported greater levels of disordered eating and dieting behaviors and attitudes
      and greater body dissatisfaction than did Asian-Americans and African-Americans
      who differed little on these measures. The nature of variability in these eating
      behaviors and attitudes and body image was also examined within each of the three
      groups. A generally consistent pattern emerged within each racial group: low self
      esteem and high public self-consciousness were associated with greater levels of
      problematic eating behaviors and attitudes and body dissatisfaction. A history of
      being teased about weight and size was associated with problematic eating
      behaviors and attitudes and body dissatisfaction in African-Americans and
      Caucasians but not in Asian-Americans. The findings suggest that there exist
      important racial differences on various aspects of eating, dieting, and body
      image in college women. Contrary to hypothesis, the degree of acculturation and
      assimilation within the African-American and Asian-American groups was unrelated
      to variability in these domains.

PMID- 7581422
TI  - Processing of threat-related information by women with bulimic eating attitudes.
AB  - It has been proposed that bulimic attitudes and behaviors serve the function of
      reducing awareness, especially where a situation is regarded as threatening.
      However, there is little evidence to support this model. Considering a non-eating
      disordered population, this study tested the prediction that a higher level of
      bulimic eating attitudes will be associated with a characteristic pattern of
      cognitive processing, where the individual is slower to respond to threatening
      information. In a computer-driven test of information processing, it was shown
      that women with more bulimic attitudes were slower to respond to threatening than
      neutral words, while there was no such effect for the women with less bulimic
      attitudes. This finding was specific to bulimic attitudes, rather than simply
      being related to unhealthy eating attitudes in general. These findings support
      the "escape from awareness" model of bulimic attitudes and behavior. Further
      research is needed, particularly to verify these findings in women with
      diagnosable bulimic disorders.

PMID- 7581425
TI  - Statistical considerations for survival analysis from medical device clinical
      studies.
AB  - Appropriate statistical methods are presented to estimate the 95% lower
      confidence limit of true event-free probability, with heavy censoring in the
      small sample size situation, and to compare crude probability, linearized rate,
      and life-table probability. The problem of survival experience extrapolation
      beyond the last observed follow-up is also discussed.

PMID- 7581426
TI  - Dissolution test acceptance sampling plans.
AB  - The U.S. Pharmacopeia (USP) general monograph provides a standard for dissolution
      compliance with the requirements as stated in the individual USP monograph for a
      tablet or capsule dosage form. The acceptance rules recommended by USP have
      important roles in the quality control process. The USP rules and their
      modifications are often used as an industrial lot release sampling plan, where a
      lot is accepted when the tablets or capsules sampled are accepted as proof of
      compliance with the requirement. In this paper, the operating characteristics of
      the USP acceptance rules are reviewed and compared to a selected modification.
      The operating characteristics curves show that the USP acceptance rules are
      sensitive to the true mean dissolution and do not reject a lot or batch that has
      a large percentage of tablets that dissolve with less than the dissolution
      specification.

PMID- 7581423
TI  - The impact of stress, fear of fatness, and panic disorder with agoraphobia on
      eating disorder symptomatology: a case study.
AB  - This case describes the interaction between an anxiety disorder and an eating
      disorder. It shows how the interplay between stress, fear of fatness, and panic
      disorder with agoraphobia changed a patient's eating disorder from bulimia
      nervosa to to an eating disorder focused on food restriction. Implications for
      the assessment and treatment of panic disorder with agoraphobia and an eating
      disorder focused on food restriction are discussed.

PMID- 7581427
TI  - The analysis of bioequivalence with respect to TMAX under a 2 x 2 crossover
      design.
AB  - We develop population-averaged and subject-specific continuation ratio logit
      models for assessing bioequivalence of two formulations with respect to TMAX
      under a 2 x 2 crossover design. We propose generalized estimating equations and
      mixed-effects estimators for obtaining confidence intervals for odds ratios
      representing population-averaged and subject-specific formulation effects. We
      show analytically that the population-averaged approach leads to asymptotic
      intervals that are narrower than the subject-specific intervals when the
      intrasubject correlation is positive. Hence, asymptotically, it is easier to show
      bioequivalence with respect to TMAX under the population-averaged approach than
      under the subject-specific approach. We illustrate these results with an analysis
      of a multiple-dose bioequivalence study.

PMID- 7581424
TI  - A two-step iterative algorithm for estimation in nonlinear mixed-effect models
      with an evaluation in population pharmacokinetics.
AB  - This article proposes an EM-like algorithm for estimating, by maximum likelihood,
      the population parameters of a nonlinear mixed-effect model given sparse
      individual data. The first step involves Bayesian estimation of the individual
      parameters. During the second step, population parameters are estimated using a
      linearization about those Bayesian estimates. This algorithm (implemented in P
      PHARM) is evaluated on simulated data, mimicking pharmacokinetic analyses and
      compared to the First-Order method and the First-Order Conditional Estimates
      method (both implemented in NONMEM). The accuracy of the results, within few
      iterations, shows the estimation capabilities of the proposed approach.

PMID- 7581428
TI  - On stability designs in drug shelf-life estimation.
AB  - In this paper, various stability designs, including matrixing and bracketing
      designs for determining drug shelf-life, are considered. We propose a criterion
      for design selection based on the precision of drug shelf-life estimates. For a
      fixed sample size, it is recommended that the design with the best precision for
      estimating the shelf-life should be used. For a fixed desired precision, the
      design with the smallest sample size is the best choice of design. An example is
      presented to illustrate the proposed method.

PMID- 7581429
TI  - Some applications of the analysis of multivariate normal data with missing
      observations.
AB  - Methods are proposed for the analysis of data from a multivariate normal
      distribution when observations are missing completely at random on some of the
      variates. Park (1) proved the equivalence of the solutions given by maximum
      likelihood and generalized estimating equations when data are complete and an
      unstructured covariance is assumed. He suggested that generalized estimating
      equations may be used if sample sizes are large relative to the amount of missing
      data and the estimated covariance matrix is positive definite. We give several
      examples indicating that the estimating equations give results similar to those
      of maximum likelihood when smoothing of the covariance matrix to eliminate
      nonpositive definiteness is not encountered as, for example, under an assumption
      of exchangeable correlation. Generalized linear models are formulated that are
      appropriate for a wide class of experimental plans.

PMID- 7581430
TI  - Clinical practice and clinical research--alias or akin?

PMID- 7581431
TI  - Exercises for chronic low back pain: a clinical trial.
AB  - Different training models are effective for the treatment of chronic low back
      pain, but no consensus has been found. Earlier studies have emphasized training
      of spinal mobility and back strength. To evaluate if other physiological
      parameters, such as coordination, are of equal importance, we performed a
      randomized trial on 40 consecutive patients with chronic low back pain. Two
      training models were compared: 1) intensive training of muscle endurance and 2)
      muscle training, including coordination. In both groups, training was performed 1
      hour twice a week for 3 months. Pain score, disability score, and spinal mobility
      improved in both training groups without differences between the two groups. Only
      intensive training of muscle endurance improved isokinetic back muscle strength.
      At study entry, we found a significant correlation between spinal mobility and
      dysfunction, but after the training, no correlation was found between improvement
      of spinal mobility or isokinetic back extension strength and improvement of
      function or pain level. We conclude that coordination training for patients with
      chronic low back pain is as equally effective as endurance training.

PMID- 7581433
TI  - A comparison of subtalar joint maximal eversion while jogging on the
      minitrampoline and floor.
AB  - The jogging minitrampoline is a common tool for exercise and rehabilitation that
      is lauded as helpful in reducing lower extremity stresses. The deformable bed of
      the minitrampoline may result in altered jogging mechanics of the subtalar joint,
      potentially leading to uncharacteristic mechanics of the lower extremity. The
      purpose of this study was to examine eversion of the subtalar joint in subjects
      jogging on the minitrampoline vs. a wooden floor surface. Subjects were
      instrumented with a flexible electrogoniometer (elgon) taped from the heel to the
      gastrocnemius along the Achilles tendon. The elgon was interfaced to a personal
      computer. Data were examined for the average maximal eversion values of five
      steps during jogging in two experiments. Results of the first experiment (N = 27)
      indicated significantly greater mean maximal eversion angles while jogging on the
      minitrampoline than on the floor. The second experiment involved 10 male and 10
      female subjects jogging for 20 minutes with a counterbalanced sequence of jogging
      conditions, alternating between the floor and the minitrampoline. The second
      experiment indicated that maximal eversion angles were significantly greater on
      the minitrampoline than on the floor and increasing jogging time resulted in
      greater eversion angles and a significant interaction between jogging condition
      and time. Results suggest that people who should avoid valgus deviations to the
      lower leg should not jog on the jogging minitrampoline.

PMID- 7581432
TI  - The effects of limb length discrepancy on subtalar joint kinematics during
      running.
AB  - Physical therapists often use videography to accurately measure joint kinematics.
      The purpose of this study was to determine how the maximal calcaneal inversion
      and eversion angles are affected while running in individuals with a limb length
      difference between 1.27 cm (1/2 inch) and 1.9 cm (3/4 inch). Twelve subjects with
      a limb length difference were videotaped using 60-Hz digitized videography while
      running on a treadmill. Data were obtained for maximum calcaneal inversion and
      eversion values. Repeated measures analyses of variance were used to determine if
      significant differences were evident between the lower extremity. Significant
      differences were not found between the short and long limb for the maximum amount
      of calcaneal inversion and eversion range of motion. Since calcaneal inversion
      and eversion are important components of subtalar joint supination and pronation,
      respectively, the results suggest that subtalar joint kinematics were not
      significantly altered.

PMID- 7581435
TI  - Prophylactic ankle bracing vs. taping: effects on functional performance in
      female basketball players.
AB  - Ankle support devices are commonly used for prevention and treatment of ankle
      injury, but the effect of these on sport performance has not been evaluated. The
      purpose of this study was to evaluate the effect of different ankle support
      devices on four basketball-related performance tests. Eleven female basketball
      players underwent four performance tests (vertical jump, jump shot, sprint drill,
      and submaximal treadmill run) while wearing five different types of ankle support
      on both ankles (no support, tape, Swede-O-Universal, Active Ankle, and Aircast).
      Ankle support effect on overall performance was assessed using Friedman's
      analysis of variance (ANOVA) by ranks and on specific performance parameters
      using one-way ANOVA for repeated measures. Overall performance was impaired by
      ankle support. The Active Ankle brace impaired performance the least out of the
      support devices. Vertical jump was less with ankle tape as compared with no tape
      (p < .05), whereas jump shot accuracy was better with tape as compared with the
      Swede-O-Universal (p < .05). Oxygen consumption (VO2) and energy expenditure were
      higher with the Aircast as compared with tape (p < .05). It was concluded that
      the use of ankle support by female basketball players does adversely affect
      basketball-related performance tests, and the prophylactic benefit of bracing
      needs to be weighed against performance impairment.

PMID- 7581434
TI  - Reliability of dynamic strength knee muscle testing in children.
AB  - The isokinetic knee test is reliable in young individuals in a broad age range
      between 6 years of age to puberty, but not specifically in the youngest subgroup,
      in which cooperation may be less dependable. Hence, the purpose of this study was
      to investigate the reliability of isokinetic knee flexor/extensor muscle torque
      in a narrow age range: 6-8 years old. The sample consisted of 12 boys tested in
      three sessions with 3 days of rest between sessions. During each session, two
      tests were performed with each knee. Intrasession correlation coefficients ranged
      between .94 and .99 for quadriceps and between .78 and .96 for hamstrings.
      Interclass correlation coefficients, which express the reliability of a single
      test, were high (ranging from .85 to .95). Analysis of variance for repeated
      measurements showed that sixfold repetition of the test had no significant effect
      on peak torque measurements. These data suggest that the isokinetic knee
      flexion/extension torque is reliable in boys 6-8 years old.

PMID- 7581436
TI  - Crimes against genetics.

PMID- 7581437
TI  - A study in scarlet.

PMID- 7581439
TI  - Complementation groups: one or more per gene?

PMID- 7581438
TI  - Myelin genes: getting the dosage right.

PMID- 7581442
TI  - Schizophrenia susceptibility and chromosome 6p24-22.

PMID- 7581440
TI  - Presenilins and Alzheimer disease.

PMID- 7581441
TI  - Schizophrenia susceptibility and chromosome 6p24-22.

PMID- 7581443
TI  - Schizophrenia susceptibility and chromosome 6p24-22.

PMID- 7581444
TI  - A chromatin model of IGF2/H19 imprinting.

PMID- 7581445
TI  - Breast cancer information on the web.

PMID- 7581446
TI  - Genetic dissection of complex traits: guidelines for interpreting and reporting
      linkage results.
AB  - Genetic studies are under way for many complex traits, spurred by the recent
      feasibility of whole genome scans. Clear guidelines for the interpretation of
      linkage results are needed to avoid a flood of false positive claims. At the same
      time, an overly cautious approach runs the risk of causing true hints of linkage
      to be missed. We address this problem by proposing specific standards designed to
      maintain rigor while also promoting communication.

PMID- 7581447
TI  - Linkage between sexual orientation and chromosome Xq28 in males but not in
      females.
AB  - We have extended our analysis of the role of the long arm of the X chromosome
      (Xq28) in sexual orientation by DNA linkage analyses of two newly ascertained
      series of families that contained either two gay brothers or two lesbian sisters
      as well as heterosexual siblings. Linkage between the Xq28 markers and sexual
      orientation was detected for the gay male families but not for the lesbian
      families or for families that failed to meet defined inclusion criteria for the
      study of sex-linked sexual orientation. Our results corroborate the previously
      reported linkage between Xq28 and male homosexuality in selected kinships and
      suggest that this region contains a locus that influences individual variations
      in sexual orientation in men but not in women.

PMID- 7581449
TI  - Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy
      with loss of the sarcoglycan complex.
AB  - The dystrophin associated proteins (DAPs) are good candidates for harboring
      primary mutations in the genetically heterogeneous autosomal recessive muscular
      dystrophies (ARMD). The transmembrane components of the DAPs can be separated
      into the dystroglycan and the sarcoglycan complexes. Here we report the isolation
      of cDNAs encoding the 43 kD sarcoglycan protein beta-sarcoglycan (A3b) and the
      localization of the human gene to chromosome 4q12. We describe a young girl with
      ARMD with truncating mutations on both alleles. Immunostaining of her muscle
      biopsy shows specific loss of the components of the sarcoglycan complex (beta
      sarcoglycan, alpha-sarcoglycan (adhalin), and 35 kD sarcoglycan). Thus secondary
      destabilization of the sarcoglycan complex may be an important pathophysiological
      event in ARMD.

PMID- 7581448
TI  - Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy
      linked to 4q12.
AB  - beta-Sarcoglycan, a 43 kDa dystrophin-associated glycoprotein, is an integral
      component of the dystrophin-glycoprotein complex. We have cloned human beta
      sarcoglycan cDNA and mapped the beta-sarcoglycan gene to chromosome 4q12.
      Pericentromeric markers and an intragenic polymorphic CA repeat cosegregated
      perfectly with autosomal recessive limb-girdle muscular dystrophy in several
      Amish families. A Thr-to-Arg missense mutation was identified within the beta
      sarcoglycan gene that leads to a dramatically reduced expression of beta
      sarcoglycan in the sarcolemma and a concomitant loss of adhalin and 35 DAG, which
      may represent a disruption of a functional subcomplex within the dystrophin
      glycoprotein complex. Thus, the beta-sarcoglycan gene is the fifth locus
      identified (LGMD2E) that is involved in autosomal recessive limb-girdle muscular
      dystrophy.

PMID- 7581450
TI  - Hypermyelination and demyelinating peripheral neuropathy in Pmp22-deficient mice.
AB  - Peripheral myelin protein PMP22 has been suggested to have a role in peripheral
      nerve myelination and cell proliferation. Defects at the PMP22 locus are
      associated with peripheral neuropathies such as Charcot-Marie-Tooth disease type
      1A. We now demonstrate that mice devoid of Pmp22 are retarded in the onset of
      myelination and develop abundant sausage-like hypermyelination structures
      (tomacula) at a young age followed by severe demyelination, axonal loss and
      functional impairment. Mice carrying one functional copy of Pmp22 are less
      affected but they also exhibit focal tomacula comparable to the morphological
      features in hereditary neuropathy with liability to pressure palsies (HNPP). We
      conclude that Pmp22 is required for the correct development of peripheral nerves,
      the maintenance of axons and the determination of myelin thickness and stability.

PMID- 7581451
TI  - Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves
      characteristic of inherited human neuropathies.
AB  - Mutations in the human gene for the myelin recognition molecule protein zero (P0)
      give rise to severe and progressive forms of dominantly inherited peripheral
      neuropathies. We have previously reported that mice homozygous for a null
      mutation in P0 have severely hypomyelinated nerves ten weeks after birth. Here we
      show hypomyelination already exists at day four with subsequent demyelination and
      impaired nerve conduction. Furthermore, heterozygous mutants show normal
      myelination, but develop progressive demyelination after four months of age.
      Thus, the pathology of homo- and heterozygous P0 mutants resembles that of the
      severely affected Dejerine-Sottas and the more mildly affected Charcot-Marie
      Tooth type 1B patients, respectively.

PMID- 7581452
TI  - A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence
      for genetic heterogeneity.
AB  - In 265 Irish pedigrees, with linkage analysis we find evidence for a
      vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score,
      assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the
      C test, also supported linkage, the strongest results being obtained with D6S296
      (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis
      yielded suggestive, but substantially weaker, findings. This locus appears to
      influence the vulnerability to schizophrenia in roughly 15 to 30% of our
      pedigrees. Evidence for linkage was maximal using an intermediate phenotypic
      definition and declined when this definition was narrowed or was broadened to
      include other psychiatric disorders.

PMID- 7581453
TI  - Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid
      organs and liver.
AB  - Fas, a type I membrane protein that transduces an apoptotic signal, is expressed
      in lymphocytes as well as in various tissues such as the liver, lung and heart.
      The mouse lymphoproliferation (lpr) mutation is a leaky mutation in Fas. By means
      of gene targeting, we generated a mouse strain which is completely deficient in
      Fas. In addition to the massive production of lymphocytes, the Fas-null mice
      showed substantial liver hyperplasia, which was accompanied by the enlargement of
      nuclei in hepatocytes. The Fas system seems to play a role in the apoptotic
      process to maintain homeostasis of the liver as well as the peripheral lymphoid
      organs.

PMID- 7581454
TI  - Evolution of the cryptic FMR1 CGG repeat.
AB  - We have sequenced the 5' untranslated region of the orthologous FMR1 gene from 44
      species of mammals. The CGG repeat is present in each species, suggesting
      conservation of the repeat over 150 million years of mammalian radiation. Most
      mammals possess small contiguous repeats (mean number of repeats = 8.0 +/- 0.8),
      but in primates, the repeats are larger (mean = 20.0 +/- 2.3) and more highly
      interrupted. Parsimony analysis predicts that enlargement of the FMR1 CGG repeat
      beyond 20 triplets has occurred in three different primate lineages. In man and
      gorilla, AGG interruptions occur with higher-order periodicity, suggesting that
      historical enlargement has involved incremental and vectorial addition of larger
      arrays demarcated by an interruption. Our data suggest that replication slippage
      and unequal crossing over have been operative during the evolution of this
      repeat.

PMID- 7581455
TI  - Developmental expression pattern screen for genes predicted in the C. elegans
      genome sequencing project.
AB  - Maximum use should be made of information generated in the genome sequencing
      projects. Toward this end, we have initiated a genome sequence-based, expression
      pattern screen of genes predicted from the Caenorhabditis elegans genome sequence
      data. We examined beta-galactosidase expression patterns in C. elegans lines
      transformed with lacZ reporter gene fusions constructed using predicted C.
      elegans gene promoter regions. Of the predicted genes in the cosmids analysed so
      far, 67% are amenable to the approach and 54% of examined genes yielded a
      developmental expression pattern. Expression pattern information is being made
      generally available using computer databases.

PMID- 7581456
TI  - Expression patterns of predicted genes from the C. elegans genome sequence
      visualized by FISH in whole organisms.
AB  - More than 10 megabases of contiguous genome sequence have been submitted to the
      databases by the Caenorhabditis elegans Genome Sequencing Consortium. To
      characterize the genes predicted from the sequence, we have developed high
      resolution FISH for visualization of mRNA distributions in whole animals. The
      high resolution and sensitivity afforded by the use of directly fluorescently
      labelled probes and confocal imaging permitted mRNA distributions to be recorded
      at the cellular and subcellular level. Expression patterns were obtained for 8
      out of 10 genes in an initial test set of predicted gene sequences, indicating
      that FISH is an effective means of characterizing predicted genes in C. elegans.

PMID- 7581459
TI  - Variants of the melanocyte-stimulating hormone receptor gene are associated with
      red hair and fair skin in humans.
AB  - Melanin pigmentation protects the skin from the damaging effects of ultraviolet
      radiation (UVR). There are two types of melanin, the red phaeomelanin and the
      black eumelanin, both of which are present in human skin. Eumelanin is
      photoprotective whereas phaeomelanin, because of its potential to generate free
      radicals in response to UVR, may contribute to UV-induced skin damage.
      Individuals with red hair have a predominance of phaeomelain in hair and skin
      and/or a reduced ability to produce eumelanin, which may explain why they fail to
      tan and are at risk from UVR. In mammals the relative proportions of phaeomelanin
      and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts
      via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin
      and the product of the agouti locus which antagonises this action. In mice,
      mutations at either the MC1R gene or agouti affect the pattern of melanogenesis
      resulting in changes in coat colour. We now report the presence of MC1R gene
      sequence variants in humans. These were found in over 80% of individuals with red
      hair and/or fair skin that tans poorly but in fewer than 20% of individuals with
      brown or black hair and in less than 4% of those who showed a good tanning
      response. Our findings suggest that in humans, as in other mammals, the MC1R is a
      control point in the regulation of pigmentation phenotype and, more importantly,
      that variations in this protein are associated with a poor tanning response.

PMID- 7581458
TI  - Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by
      multipoint affected sib-pair linkage analysis.
AB  - The influence of genetic factors in schizophrenia has been convincingly
      demonstrated by family, twin and adoption studies, but the mode of transmission
      remains uncertain. The reported pattern of recurrence risks suggests a set of
      interacting loci. Based on prior evidence for linkage on chromosome 6p (K.
      Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54
      families for loci predisposing to schizophrenia, using 25 microsatellite markers
      spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in
      affected sib-pairs from these families, followed by multipoint sib-pair linkage
      analysis. Positive lod scores were obtained over a wide region (D6S470 to
      D6S271), with a maximum lod score of 2.2 occurring near D6S274, located in 6p22.
      However, we obtained a lod score of -2 at D6S296, the locus found by others to
      provide the greatest linkage evidence. At D6S274, we report a positive lod score
      as do Straub et al. (individually non-significant). A combined total lod of 3.6
      4.0 suggests the possibility of a susceptibility locus in this region. However,
      methodological differences between our studies makes a firm conclusion difficult.

PMID- 7581460
TI  - Contribution of the FMR1 gene mutation to human intellectual dysfunction.
AB  - The degree to which genetic factors influence human intelligence remains a matter
      of some controversy. However, there is little doubt that single gene mutations
      can significantly alter brain development and function. For example, mutations
      affecting the FMR1 gene cause the fragile X syndrome, the most prevalent known
      inherited cause of intellectual dysfunction. The most common mutation occurring
      in the FMR1 locus involves expansion of a trinucleotide (CGG)n repeat sequence
      within the promoter region of the gene. Between 6 and 54 repeats are typically
      observed in individuals from the general population. When > or = 200 CGG repeats
      are present, the expanded repeat sequence and an adjacent CpG island are usually
      hypermethylated, Aa phenomenon associated with transcriptional silencing of the
      gene and commonly referred to as the FMR1 full mutation. The intermediate range
      of repeats (approximately 50 to 200 CGGs), referred to as the premutation, is
      characterized by the absence of hypermethylation within the promoter region and
      normal phenotype. Some individuals have a combination of methylated and
      unmethylated alleles of differing size and are referred to as having mosaic
      status. Most males with the FMR1 full mutation function in the mentally retarded
      range of intelligence; in contrast, females with the FMR1 full mutation show a
      broader range of intelligence, from mental retardation to normal IQ.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581457
TI  - An international two-stage genome-wide search for schizophrenia susceptibility
      genes.
AB  - Schizophrenia is thought to be a multifactorial disease with complex mode of
      inheritance. Using a two-stage strategy for another complex disorder, a number of
      putative IDDM-susceptibility genes have recently been mapped. We now report the
      results of a two-stage genome-wide search for genes conferring susceptibility to
      schizophrenia. In stage I, model-free linkage analyses of large pedigrees from
      Iceland, a geographical isolate, revealed 26 loci suggestive of linkage. In stage
      II, ten of these were followed-up in a second international collaborative study
      comprising families from Austria, Canada, Germany, Italy, Scotland, Sweden,
      Taiwan and the United States. Potential linkage findings of stage I on
      chromosomes 6p, 9 and 20 were observed again in the second sample. Furthermore,
      in a third sample from China, fine mapping of the 6p region by association
      studies also showed evidence for linkage or linkage disequilibrium. Combining our
      results with other recent findings revealed significant evidence for linkage to
      an area distal of the HLA region on chromosome 6p. However, in a fourth sample
      from Europe, the 6p fine mapping finding observed in the Chinese sample could not
      be replicated. Finally, evidence suggestive of locus heterogeneity and oligogenic
      transmission in schizophrenia was obtained.

PMID- 7581461
TI  - A frame-shift deletion in the survival motor neuron gene in Spanish spinal
      muscular atrophy patients.
AB  - Spinal muscular atrophy (SMA) is a frequent autosomal recessive disease
      characterized by degeneration of the motor neurons of the spinal cord causing
      proximal paralysis with muscle atrophy. The region on chromosome 5q13
      encompassing the disease gene is particularly unstable and prone to large-scale
      deletions whose characterization recently led to the identification of the
      survival motor neuron (SMN) gene. We now present a genetic analysis of 54
      unrelated Spanish SMA families that has revealed a 4-basepair (bp) deletion
      (AGAG) in exon 3 of SMN in four unrelated patients. This deletion, which results
      in a frameshift and a premature stop codon, occurs on the same haplotype
      background, suggesting that a single mutational event is involved in the four
      families. The other patients showed either deletions of the SMN gene (49/54) or a
      gene conversion event changing SMN exon 7 into its highly homologous copy
      (cBCD541, 1/54). This observation gives strong support to the view that mutations
      of the SMN gene are responsible for the SMA phenotype as it is the first
      frameshift mutation reported in SMA.

PMID- 7581462
TI  - Localisation of the Fanconi anaemia complementation group A gene to chromosome
      16q24.3.
AB  - Fanconi anaemia (FA) is an autosomal recessive disorder associated with diverse
      developmental abnormalities, bone-marrow failure and predisposition to cancer. FA
      cells show increased chromosome breakage and hypersensitivity to DNA cross
      linking agents such as diepoxybutane and mitomycin C. Somatic-cell hybridisation
      analysis of FA cell lines has demonstrated the existence of at least five
      complementation groups (FA-A to FA-E), the most common of which is FA-A. This
      genetic heterogeneity has been a major obstacle to the positional cloning of FA
      genes by classical linkage analysis. The FAC gene was cloned by functional
      complementation, and localised to chromosome 9q22.3 (ref. 2), but this approach
      has thus far failed to yield the genes for the other complementation groups. We
      have established a panel of families classified as FA-A by complementation
      analysis, and used them to search for the FAA gene by linkage analysis. We
      excluded the previous assignment by linkage of an FA gene to chromosome 20q, and
      obtained conclusive evidence for linkage of FAA to microsatellite markers on
      chromosome 16q24.3. Strong evidence of allelic association with the disease was
      detected with the marker D16S303 in the Afrikaner population of South Africa,
      indicating the presence of a founder effect.

PMID- 7581463
TI  - Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to
      chromosome 3p.
AB  - Fanconi anaemia (FA) is an autosomal recessive disorder characterized by
      progressive pancytopenia, short stature, radial ray defects, skin
      hyperpigmentation and a predisposition to cancer. Cells from FA patients are
      hypersensitive to cell killing and chromosome breakage induced by DNA cross
      linking agents such as mitomycin C (MMC) and diepoxybutane (DEB). Consequently,
      the defect in FA is thought to be in DNA crosslink repair. Additional cellular
      phenotypes of FA include oxygen sensitivity, poor cell growth and a G2 cell cycle
      delay. At least 5 complementation groups for Fanconi anaemia exist, termed A
      through E. One of the five FA genes, FA(C), has been identified by cDNA
      complementation, but no other FA genes have been mapped or cloned until now. The
      strategy of cDNA complementation, which was successful for identifying the FA(C)
      gene has not yet been successful for cloning additional FA genes. The alternative
      approach of linkage analysis, followed by positional cloning, is hindered in FA
      by genetic heterogeneity and the lack of a simple assay for determining
      complementation groups. In contrast to genetic linkage studies, microcell
      mediated chromosome transfer utilizes functional complementation to identify the
      disease bearing chromosome. Here we report the successful use of this technique
      to map the gene for the rare FA complementation group D (FA(D)).

PMID- 7581464
TI  - Deficiency of the beta 3 subunit of the type A gamma-aminobutyric acid receptor
      causes cleft palate in mice.
AB  - In addition to its function in the nervous system, gamma-aminobutyric acid (GABA)
      has been implicated in mouse craniofacial development by the results of both
      teratological, and genetic studies. We previously reported that disruption of the
      cleft palate 1 (cp1) locus, closely linked to the pink-eyed dilution (p) locus on
      mouse chromosome 7, causes a 95% penetrant, recessive, neonatally-lethal cleft
      palate (CP) in mice homozygous for the p(4THO-II) deletion. We proposed that the
      beta 3 subunit gene (Gabrb3) of the GABAA receptor might be a candidate for cp1
      (ref. 4); our earlier studies had localized cp1 to an interval beginning distal
      to the gene for the GABAA receptor alpha 5 subunit (Gabra5) and ending within the
      Gabrb3 coding region. To test the hypothesis that deletion of Gabrb3, and not
      another gene in the interval, causes CP, we performed an experiment to rescue the
      CP phenotype by introducing a Gabrb3 transgene into p(4THO-II) homozygotes. We
      now show that such transgenic mice are phenotypically normal, indicating that
      Gabrb3 is indeed the cp1 locus.

PMID- 7581465
TI  - Widespread expression of the testis-determining gene SRY in a marsupial.
AB  - There is compelling evidence from mutation analysis and transgenesis that the SRY
      gene isolated from human and mouse encodes the testis-determining factor on the
      mammalian Y chromosome. However, how SRY achieves this function is unclear.
      Although marsupials have been separated from eutherian mammals for approximately
      100 million years, homologues of SRY have been localised to the Y chromosome of
      two unrelated marsupial species, the tammar wallaby and the Darling Downs
      dunnart. Gonadal development is fundamentally similar in eutherian and marsupial
      mammals, but the timing of morphological events is different. Fetal Sry
      transcripts are confined to somatic cells of the male mouse genital ridge between
      10.5-12.5 days post coitum, corresponding with the onset of testis
      differentiation. Analysis of Sry gene expression in the genital ridge of normal
      and germ cell-deficient fetal mice has established that this gene acts in the
      somatic cell lineage, and is presumed to induce the formation of Sertoli cells.
      This assumption can be tested more critically in the tammar, where the equivalent
      stages of testis differentiation are observed over a 7-day period. We have
      examined the relationship of SRY expression to testis differentiation in the
      tammar wallaby. We show the marsupial SRY gene cannot be exclusively coupled to
      Sertoli cell differentiation, as this gene is expressed in the male fetus from
      several days before genital ridge formation until 40 days after birth. SRY
      transcripts are also present in a variety of extra-gonadal tissues in the
      developing young and adult male, a pattern of SRY expression similar to that
      observed in humans. These data indicate that, in addition to a role in testis
      determination, SRY may have other functions [corrected].

PMID- 7581466
TI  - Long-term results and complications using augmentation cystoplasty in
      reconstructive urology.
AB  - One hundred and twenty-two augmentation cystoplasties performed over an 8-year
      period were reviewed. Mean age at surgery was 37 years (range 2-82 years). There
      were 82 female patients. The primary urodynamic diagnosis was reduced compliance
      in 92 (77%) patients and detrusor hyperreflexia/instability in the remainder. The
      clinical diagnostic groups were: spinal cord injury/disease in 32 (27%),
      myelodysplasia in 27 (22%), interstitial cystitis in 21 (17%), idiopathic
      detrusor instability in 13 (11%), radiation cystitis in 8 (7%), Hinman-Allen
      syndrome in 5 (4%), and miscellaneous in 11 (9%). A detubularized ileal
      augmentation was used in 82 (67%) patients. In 36 (30%) a detubularized
      ileocecocystoplasty was fashioned and in the remainder detubularized sigmoid was
      used. In 19 patients augmentation accompanied undiversion. Sixteen patients had a
      simultaneous fascial sling for urethral incompetence. Mean follow-up was 37
      months (range 6-96 months). There was no postoperative mortality. During follow
      up 4 patients died from unrelated causes, 11 have been lost to follow-up, and 5
      patients await planned transplantation. Bladder capacity was increased from a
      preoperative mean of 108 ml (range 15-500 ml) to 438 ml (200-1,200 ml)
      postoperatively. Of the 106 assessable patients, 80 (75%) had an excellent
      result, 21 (20%) were improved, and 5 (5%) had major ongoing problems. During the
      period of follow-up, 17 (16%) patients underwent revision of their augmentation.
      Twenty-four (21%) patients developed bladder stones and 30% of these did so more
      than once. Urinary incontinence became manifest in 15 (13%) patients but required
      surgical treatment in only half of these. Pyelonephritis occurred in 13 (11%)
      patients. Five patients developed small bowel obstruction following discharge
      from hospital. There were 7 instances of reservoir rupture in 5 (4%) patients.
      Augmentation cystoplasty has a pivotal role in the treatment of a broad range of
      lower and upper urinary tract problems. Careful patient selection and close
      follow-up are essential.

PMID- 7581467
TI  - Comparison of "subjective" and "objective" measures of severity of urinary
      incontinence in women. Program for Women Research Group.
AB  - The aims of this study were to compare "subjective" measures of severity of
      urinary incontinence to similar "objective" measures, establish their statistical
      correlation, and determine the effect of specific urodynamic diagnosis on such
      correlations. Baseline data was available from 265 women entered into a clinical
      trial studying pharmacologic and behavioral interventions for urinary
      incontinence. The "subjective" measures of incontinence were obtained by patient
      recall during history taking and included: the number of incontinent episodes in
      1 week, the number of perineal pads used during 1 week, and the number of
      clothing changes required due to wetness. The "objective" measures of severity
      included: the number of incontinent episodes per week as recorded on a 7-day
      diary, the number of perineal pads used per week, also recorded on a diary, and
      the amount of fluid lost during a standardized pad test. Analysis consisted of
      Pearson correlations and linear regressions to determine equations for the
      prediction of objective measurement on the basis of the corresponding subjective
      measure. Significant positive correlations were seen between "subjective" and
      "objective" measurements for the comparisons of number of weekly incontinent
      episodes (R = 0.63), and for the weekly number of pads used (R = 0.81). The
      comparison between the number of clothing changes and the amount of fluid lost
      during pad testing was also significantly but less strongly correlated (R =
      0.24). For the correlations between subjective and objective determinations of
      urinary incontinent episodes and for those between clothing changes and pad
      testing, the urodynamic diagnosis had no effect on the correlation coefficients,
      but did have a statistically significant effect on the intercept.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581468
TI  - Some observations on a condition of relatively lower detrusor contractility in
      stable versus unstable unobstructed bladders.
AB  - The study comprised 30 consecutive benign prostatic hypertrophy patients--15 with
      detrusor instability, and 15 with stable bladders--who had a relatively lower
      detrusor contractility with no obvious obstruction of the vesical outlet.
      Compared with the stable bladders, those with detrusor instability showed lower
      filling volumes, along with a relatively greater voiding efficiency and
      relatively higher values of detrusor contraction strength and contraction
      velocity. Micturition contractions proved to be more well sustained until the end
      of voiding in the unstable group. It has been assumed that the factors
      responsible for detrusor instability also caused bladder contractile capability
      to relatively increase. In other words, it seemed even this extreme case could
      possibly support the view that detrusor instability always involves a tendency to
      enhanced contractile function.

PMID- 7581469
TI  - New method to quantify the urodynamic improvement when treating bladder outlet
      obstruction: the efficacy of transurethral resection in benign prostatic
      hypertrophy.
AB  - A method to measure the urodynamic improvement when treating urethral obstruction
      is introduced and applied to patients with benign prostatic hypertrophy. The
      patients performed pressure-flow studies before and 3-6 months after TUR-p. The
      urethral resistance relation was estimated by curve fitting in the pressure flow
      plot. The new method quantifies the improvement in urethral resistance as the
      distance between the urethral resistance relation before and after treatment
      expressed in pressure units. The distance is measured at the flow rate equal to
      75% of the maximum flow rate for the micturition with the lowest maximum flow
      rate and this distance is called delta-URA. The median improvement after TUR-p
      was 71 cm H2O (range 2-119). The improvement was strongly correlated to the
      resistance before treatment and the regression line indicates that the operation
      normalizes the resistance irrespective of its preoperative value. On the average
      a lowering of the urethral resistance relation with 8 cm H2O improved the maximum
      flow rate with 1 ml/s. The greatest advantage with the new method is that it has
      a high validity and is almost completely insensitive to changes in contractility.

PMID- 7581470
TI  - Urethral pressure increase on effort originates from within the urethra, and
      continence from musculovaginal closure.
AB  - The aim of the study was to determine the contribution of intra-abdominal
      pressure transmission to urinary continence in the female. Five patients with
      genuine stress incontinence (GSI) were studied. Pressure transmission was
      measured in equivalent positions inside and outside the urethra and bladder
      during the Intravaginal Slingplasty procedure, a surgical operation used for
      treatment of urinary incontinence, and performed under local anaesthesia. A 6 mm
      diameter channel was created alongside the urethra. Two separate microtransducer
      catheters appropriately marked for length were inserted, one inside the urethra,
      and the other inside the described channel. With the vaginal hammock intact, an
      average of 10 simultaneous pressure measurements were made intraoperatively in
      response to coughing and straining in equivalent positions inside the urethra,
      and directly outside. Significantly higher pressure readings were found inside
      the urethra (P = 0.0025), indicating that an active component within the urethra
      may have created this pressure rise. After opening out two suburethral vaginal
      flaps, large quantities of urine were lost on coughing in all patients.
      Continence was achieved on tightening the suburethral vagina, indicating that an
      adequately tight vaginal hammock is a critical element in the continence process.
      The findings of this study question intraabdominal pressure as a mechanism
      contributing to continence, but support an alternative mechanism, musculovaginal
      closure of the urethra.

PMID- 7581471
TI  - Transurethral sphincterotomy in quadriplegic patients: long-term-follow-up.
AB  - Sphincterotomy was the treatment of choice in spinal cord injured patients with
      reflex bladder activity and detrusor sphincter dyssynergia after World War II.
      However, nowadays the conversion of a spastic bladder into a low pressure
      reservoir by medication or operatively has become a more favourable bladder
      management. Only in quadriplegic patients who are not able to perform self
      catheterization, this treatment modality seemed to be an alternative. With twelve
      o'clock sphincterotomy, urodynamic parameters of the lower urinary tract can be
      brought to favourable measures (leak-point, residuals). However, the reoperation
      rate for the maintenance of these urodynamic results is high (57%). Laser
      sphincterotomy seems to be advantageous in this respect, as it reduces the need
      for resphincterotomy significantly. Additionally, 14% of the patients needed
      operations, which made condom fixation possible. Upper tract could only be
      preserved if sphincterotomy is done early enough. Patients who do not empty
      completely while in the wheelchair are at risk to develop a hydronephrosis.

PMID- 7581472
TI  - Transrectal ultrasound guided needle electromyography of the urethral sphincter
      in males.
AB  - Needle electromyography (EMG) of the urethral sphincter in males is commonly
      performed using a transperineal approach. The technique involves transcutaneous
      insertion of an EMG needle into the sphincter guided by the investigator's finger
      placed in the rectum. We describe a new method of needle placement into the
      urethral sphincter in males using transrectal ultrasound (TRUS). With the patient
      in the left lateral position, the apex of the prostate gland is identified in the
      longitudinal plane. Using the TRUS biopsy channel, a specially designed long EMG
      needle is inserted into the sphincter commencing approximately 1.5-2 cm distal to
      the prostatic apex in an oblique fashion. This method allows precise
      identification of the site for needle insertion, reducing blind attempts at
      localization. The transrectal route is much less uncomfortable to patients,
      potentially improving patient compliance and overall effectiveness of the
      technique.

PMID- 7581473
TI  - New and simplified vaginal approach for correction of urinary stress incontinence
      in women.
AB  - Twenty-four patients with urodynamically confirmed urinary stress incontinence
      were operated upon with a new and simplified vaginal approach. This new technique
      is a simplification of a previously described transabdominal surgical method, in
      which a two-component fibrin sealant (Tisseel) was used. The sealant resulted in
      an excess of fibrin, which induced fibrosis, securing the urethrovesical junction
      in an elevated position to the retropubic periosteum. In the present study, the
      sealant was deposited retropubically with a specially designed needle through the
      anterior vaginal wall. A great advantage with this procedure is that only local
      anesthesia is used and the patient can leave the outpatient clinic 1 hour after
      the operation. The minimum duration of the follow-up period was 18 months. The
      success rate was as high as 63%, and no side effects were observed.

PMID- 7581474
TI  - Preliminary report: detrusor hyperreflexia in schizophrenia.
AB  - The object of this study was to demonstrate detrusor hyperreflexia (DH) in
      schizophrenic patients. Twelve consecutive schizophrenic patients were evaluated
      by DSM-IIIR diagnostic criteria and other standard psychiatric measures,
      urological history and examination, and urodynamic study. All were referred for
      clinical indication, voiding dysfunction, or incontinence. Two patients were
      excluded for confounding variables, mental retardation and benign prostatic
      hypertrophy. Of the ten evaluable patients, four had DH. Detrusor hyperreflexia
      does occur in a subset of schizophrenic patients, even in the absence of other
      recognized disease to explain the occurrence. This relationship, previously
      unreported, warrants further investigation.

PMID- 7581476
TI  - International Continence Society 25th annual meeting. Sydney, Australia, 17-20
      October 1995. Abstracts.

PMID- 7581477
TI  - Proceedings of the 14th Sapporo Cancer Seminar on genetic polymorphism and cancer
      susceptibility. 6-9 July 1994.

PMID- 7581475
TI  - Length density and total length of acetylcholinesterase positive nerves related
      to cystometry and in vitro studies of muscle strips in mini-pig urinary bladder
      after chronic outflow obstruction and recovery from obstruction.
AB  - Chronic partial bladder outlet obstruction was created in mini-pigs by implanting
      a 6-7 mm ring around the proximal urethra. After a median obstruction period of
      63 days, the ring was removed and after a median recovery period of 60 days the
      animals were sacrificed. At each occasion stepwise cystometry, measurement of
      residual urine, muscle strips studies with electrical and carbachol stimulation,
      and stereological estimations of length density and total length of
      acetylcholinesterase positive nerves were performed. The results can be
      summarized as follows: (1) unchanged sensitivity of muscle strips to carbachol,
      but markedly decreased contractility and rate of contraction to carbachol, (2) no
      evidence of detrusor instability, but severely decompensated bladders in two
      pigs, (3) a significant increase in residual volume, (4) a pronounced decrease in
      length density and total length of acetylcholinesterase positive nerves, and (5)
      at field stimulation strips from some pigs showed increased sensitivity and
      contractility with high atropine and TTX resistance, while strips from the other
      pigs revealed decreased sensitivity and markedly decreased contractility to
      electrical stimulation. In general, most of the changes were markedly, though
      incompletely, reversed after recovery. Light and electron microscopy of muscle
      strips showed no histological or ultrastructural changes during the experiments
      or after storing 1 day at 4 degrees C.

PMID- 7581478
TI  - Conjugation of carcinogens by theta class glutathione s-transferases: mechanisms
      and relevance to variations in human risk.
AB  - Conjugation of chemicals with glutathione (GSH) can lead to decreased or
      increased toxicity. A genetic deficiency in the GSH S-transferase mu class gene
      M1 has been hypothesized to lead to greater risk of lung cancer in smokers.
      Recently a gene deletion polymorphism involving the human theta enzyme T1 has
      been described: the enzyme is present in erythrocytes and can be readily assayed.
      A rat theta class enzyme, 5-5, has structural and catalytic similarity and the
      protein was expressed in the Salmonella typhimurium tester strain TA1535.
      Expression of the cDNA vector increased the mutagenicity of ethylene dibromide
      and several methylene dihalides. Mutations resulting from the known GSH S
      transferase substrate 1,2-epoxy-3-(4'nitrophenoxy)propane were decreased in the
      presence of the transferase. Expression of transferase 5-5 increased mutations
      when 1,2,3,4-diepoxybutane (butadiene diepoxide), 4-bromo-1,2-epoxybutane, or 1,3
      dichloracetone were added. The latter compound is a model for the putative 1,2
      dibromo-3-chloropropane oxidation product 1-bromo-3-chloroacetone. These
      genotoxicity and genotyping assays may be of use in further studies of the roles
      of GSH S-transferase theta enzymes in bioactivation and detoxication and any
      changes in risk due to polymorphism.

PMID- 7581479
TI  - Metabolic polymorphisms and carcinogen-DNA adduct formation in human populations.
AB  - Metabolic polymorphisms have long been recognized as important determinants of
      carcinogen susceptibility and recent efforts have shown that interindividual
      differences in specific cytochromes P450, acetyltransferases, sulfotransferases
      and glutathione S-transferases are often disproportionately represented in
      epidemiological studies between cancer cases and controls. Concomitantly,
      biomonitoring of carcinogen-DNA adducts in human tissues using immunochemical,
      32P-postlabelling, fluorescence, and mass spectrometric methods have recently
      provided direct evidence of human exposure to genotoxic aromatic and heterocyclic
      amines, polycyclic hydrocarbons, alkylating agents, and endogenous products.
      However, a combined approach is now needed in order to assess the relevance of
      these findings to cancer etiology, to identify high-risk individuals, and to
      provide better health monitoring, earlier diagnosis, and cancer prevention. Using
      this paradigm, results are presented that implicate specific aromatic amines,
      heterocyclic amines, and polycyclic aromatic hydrocarbons in the etiology of
      human urinary bladder, colon, and laryngeal cancers.

PMID- 7581480
TI  - Detection of primary DNA damage: applicability to biomonitoring of genotoxic
      occupational exposure and in clinical therapy.
AB  - The biological effect of putative genotoxic chemicals in the work place
      environment was monitored in peripheral mononuclear blood cells of exposed
      workers. DNA strand breaks, alkali-labile sites of DNA and DNA cross-links were
      measured using the alkaline filter elution method. A dose dependent increase in
      DNA damage was found in sterilization workers exposed to ethylene oxide and metal
      workers with exposure towards N-nitrosodiethanolamine. Two subpopulations with
      different response to the external exposure were found in nonsmoking
      sterilization workers. Nurses handling antineo-plastic agents without adequate
      safety provisions showed a statistically significantly higher rate of DNA strand
      breaks compared to other nurses handling cytostatic drugs with recommended safety
      equipment and also compared to not exposed controls. Also in several other
      occupational groups such as fire fighters possibly exposed to several genotoxic
      chemicals after an accident in a chemical plant, roofers and petrol pump
      attendants a significantly higher amount of DNA damage was found compared to
      controls. No statistically significant differences in the amount of DNA strand
      breaks were found in cabinet makers and car mechanics compared to controls. In
      peripheral mononuclear blood cells of ovarial carcinoma patients as well as of
      patients with Morbus Hodgkin an increased DNA strand break rate was found after
      application of cytostatic drugs. The individual patients showed a very different
      response after drug intake. The increase in DNA damage after drug application is
      possibly related to the success of the chemotherapy.

PMID- 7581482
TI  - Lung cancer and CYP2D6 (the debrisoquine polymorphism): sources of heterogeneity
      in the proposed association.
AB  - Lung cancer association studies have yielded suggestive but not definitive
      results for a few genes: CYP1A1 (in Japanese), GSTM1 and CYP2D6. We focus on
      variability in studies of lung cancer and the CYP2D6 gene (debrisoquine metabolic
      phenotype) as an instructive case and we propose some sources for this
      heterogeneity. Beyond the general sources of bias in all field studies, three
      specific concerns are relevant. First, evidence that CYP2D6 is expressed in the
      brain. The metabolic phenotypes have distinct psychological profiles and
      therefore there is the potential to distort studies through selection bias.
      Second, among the lung cancer histologic types, adenocarcinoma likely does not
      share increased genetic susceptibility due to CYP2D6. Third, the degree of
      smoking is likely to be related to genetic susceptibility. Effect modification by
      smoking should be sought for any putative genetic marker for lung cancer.
      Progress in understanding genetic susceptibility is likely to depend on future
      well-designed studies that adjust for these and other sources of bias. We are
      currently reanalyzing the original data from the published studies in order to
      further explore these issues.

PMID- 7581481
TI  - The CYP2A gene subfamily: species differences, regulation, catalytic activities
      and role in chemical carcinogenesis.
AB  - The CYP2A subfamily has been characterized in several mammalian species including
      mouse, rat, rabbit, hamster, cattle and human. Marked species differences have
      been demonstrated in the catalytic activities and regulation of this subfamily.
      In humans, the CYP2A genes are found as a cluster on the long arm of chromosome
      19 with the CYP2B and CYP2F genes. Marked interindividual differences in
      expression of the CYP2A6 gene was found in livers analyzed in vitro and in humans
      phenotyped in vivo by using coumarin, a specific substrate for the enzyme.
      Efforts are underway to determine the existence of mutant and variant CYP2A6
      alleles in the human population. Since CYP2A6 is able to metabolically-activate
      chemical carcinogens and is expressed in extrahepatic tissue, it will be of
      interest to determine whether genetic differences in expression of the gene is
      associated with cancer risk.

PMID- 7581483
TI  - Primary structures and properties of two related forms of aryl sulfotransferases
      in human liver.
AB  - cDNAs and genes of ST1A2 and ST1A3 section were isolated from human liver cDNA
      and genomic libraries and shown to encode arylsulfotransferases. Studies on their
      mRNAs and proteins expressed indicate the existence of two distinct phenol
      sulfating enzymes which are involved in the metabolic activation of carcinogenic
      arylamines in human livers.

PMID- 7581485
TI  - CYP1A1 and CYP2E1 polymorphism and lung cancer, case-control study in Rio de
      Janeiro, Brazil.
AB  - Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP1A1, and Rsa I
      polymorphism of CYP2E1 were studied in lung cancer patients and controls in Rio
      de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7
      polymorphism of CYP1A1 (Val-containing genotypes) had a distribution which was
      statistically significant in the patients and controls. The contribution of Val
      containing genotypes of CYP1A1 exon 7 was greater in the subpopulation of
      squamous cell carcinoma patients with a lower life-time smoking consumption (OR,
      2.92 vs 1.97). This association is consistent with the previous findings by
      Kawajiri et al. and the first observation of the positive association of this
      locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K,
      Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore,
      together with the lack of association of Msp I polymorphism in the non-coding
      region of CYP1A1, the locus truly responsible for lung cancer risk among pleural
      polymorphisms of CYP1A1 appeared to be exon 7 Ile-Val polymorphism. In the
      future, investigations of multiple markers in different ethnic populations may
      reveal cancer risk markers common to all mankind.

PMID- 7581484
TI  - Cytochrome P4502E1 (CYP2E1) genetic polymorphism in a case-control study of
      gastric cancer and liver disease.
AB  - Cytochrome P4502E1 (CYP2E1) activates carcinogenic N-nitrosamines, benzene,
      urethane and other low molecular weight compounds. This enzyme is also inducible
      by ethanol, and metabolizes alcohol. A restriction fragment length polymorphism
      (RFLP) using the Rsa I restriction enzyme has been identified in the CYP2E1
      transcription regulatory region; recent studies suggest that this polymorphism
      may affect gene expression. We investigated the frequency of the Rsa I RFLP in a
      Japanese population in relation to gastric cancer and liver disease
      susceptibility. The frequency of this polymorphism was determined in 150 gastric
      cancer, 16 hepatocellular cancer, 48 liver cirrhosis and 203 benign gastric
      disease (controls) patients. This preliminary study shows no association of the
      specific genotype with gastric cancer in all subjects (odds ratio = 1.04, 95% CI
      = 0.74-3.08 for the heterozygote and 0.57, 95% CI = 0.22-1.50 for the homozygous
      rare allele, respectively). To further confirm this lack of association, an age
      and gender matched case-control study should be performed. Separately, there was
      no association of the Rsa I RFLP with hepatocellular carcinoma (p = 0.911), but
      there was a suggested difference between the non-viral associated liver cirrhosis
      patients and control patients. Thus, this polymorphism may be related to ethanol
      metabolism and consequential liver diseases in a Japanese population.

PMID- 7581486
TI  - Polymorphic forms of the Ah receptor and induction of the CYP1A1 gene.
AB  - Induction of cytochrome P4501A1 (CYP1A1) by certain xenobiotics is mediated by
      the Ah receptor/Arnt complex. The present knowledge about the molecular process
      of induction is summarized with special attention to our recent work on
      characterization of the polymorphic forms of the Ah receptor.

PMID- 7581487
TI  - Assessment of cancer susceptibility in humans by use of genetic polymorphisms in
      carcinogen metabolism.
AB  - Prevention is an important and effective measure for reducing death caused by
      cancer. Thus information on individual susceptibility to cancer is valuable in
      suggesting high risk individuals to avoid intake of carcinogenic substances and
      receive frequent physical screening. To this end, polymorphisms found within
      cytochrome P450 (CYP) genes implicated in the metabolism of procarcinogens are
      expected to be good genetic targets in assessing human cancer susceptibility. We
      have found polymorphisms in the CYP2E1 and CYP1A1 genes associated with lung
      cancer susceptibility, though there were some discrepancies from observations
      made by other investigators. Discrepancies among investigators from different
      regions, however, are very common in these pharmacogenetic studies. We present an
      explanation for these discrepancies, difficulties associated with prediction of
      relative risk of individuals, and future directions.

PMID- 7581489
TI  - Implication of nitric oxide synthase in carcinogenesis: analysis of the human
      inducible nitric oxide synthase gene.
AB  - Nitric oxide (NO) is a newly identified, multifunctional biological mediator.
      However, it also has deleterious effects on biological materials. For instance,
      nucleic acids, proteins, and some prosthetic groups of enzymes can be modified by
      NO or its reaction products with other reactive oxygen species. Endogenous
      nitrosamine formation through the reaction of NO or its oxidized products with
      amines might be involved in carcinogenesis. These deleterious effects of NO are
      often associated with inflammatory processes both in experimental animals and
      human. We analyzed the molecular mechanism of control of expression of the
      inducible nitric oxide synthase (NOS) gene in mouse cells by cloning its putative
      promoter region. This promoter responded to various cytokines and endotoxin
      similarly to the endogenous NOS gene in mouse cells. No appreciable induction of
      NOS was observed in human peripheral blood cells, but induction was detected in a
      human glioblastoma cell line A-172. Therefore, the human inducible NOS cDNA was
      cloned from A-172 cells and its cDNA-deduced amino acid sequence found to have
      about 80% similarity to those of both mouse and rat inducible NOSs. The effects
      of various cytokines on the induction of the gene were somewhat different from
      those observed in mouse cells, but the mouse promoter responded to these
      cytokines similarly to the endogenous NOS gene in human cells, indicating
      functional similarity of cis-elements of the genes encoding both human and mouse
      inducible NOS. Structural analysis of the human inducible NOS gene by Southern
      blot analysis revealed putative genetic restriction fragment length polymorphism
      in intron 5.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581488
TI  - Genetic polymorphisms and susceptibility to cancer development.
AB  - Humans show heterogeneous susceptibility to cancer development, suggesting the
      involvement of various genetic backgrounds in control of the production of
      endogenous carcinogens, the metabolism of carcinogens, the repair of DNA damage,
      cell proliferation and defence mechanisms including immune reactions. Gastric
      cancer is the major cancer in Japan. However, little is known about the genes
      linked with its development. In 1967, we found that N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) induced gastric cancers in Wistar rats. Subsequently the
      Buffalo strain of rats was reported to be resistant to MNNG stomach
      carcinogenesis, while ACI rats were very sensitive. In a carcinogenesis study
      using F1 and F2 rats, we suggested that this trait of MNNG stomach carcinogenesis
      resistance was regulated by a single autosomal dominant allele. The O6
      methylguanine adduct levels in gastric mucosa induced by MNNG were the same in
      Buffalo and ACI rats, but cell proliferation induced by MNNG was much higher in
      ACI than Buffalo animals. Chromosome mapping of the gene responsible for
      susceptibility to MNNG-induced carcinogenesis is now in progress and its
      identification will hopefully give us clues to the involvement of genetic traits
      in susceptibility to gastric cancer in humans. In addition, the genetic
      background of susceptibility to breast cancer is also being studied. In Japan,
      about 5% of all cases of breast cancer are familial. We have studied BRCA1, the
      breast cancer susceptibility gene, as a determinant of susceptibility to breast
      cancer by linkage analyses in 11 families, but our results indicate that BRCA1
      may not be important for development of familial breast cancer in
      Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581490
TI  - Molecular biomarkers for aflatoxins and their application to human liver cancer.
AB  - The rationale for developing molecular biomarkers to monitor and assess risk from
      human exposure to aflatoxins have been justified by the association of these
      carcinogens with human liver cancer, a disease that causes at least 250000 deaths
      world-wide each year. The goal of our research has been the development of
      aflatoxin biomarkers based upon the knowledge of the biochemistry and toxicology
      of aflatoxins gleaned from both experimental and human studies. These biomarkers
      have been subsequently utilized in experimental chemoprotection models to provide
      data on the modulation of these markers under different situations of disease
      risk. Several of the aflatoxin specific biomarkers have been validated in
      epidemiologic studies and are now available to use as intermediate biomarkers in
      chemoprotection trials. This systematic approach provides encouragement for
      preventive interventions and should serve as a template for the development,
      validation and application of other chemical-specific biomarkers to cancer or
      other chronic diseases.

PMID- 7581491
TI  - Molecular and epidemiological analyses of abnormal expression of aromatase in
      breast cancer.
AB  - One-third of human breast cancers exhibit estrogen-dependent proliferation. It
      appears that estrogen functions as a mitogenic factor in these carcinomas. As
      aromatase is the rate-limiting enzyme in estrogen biosynthesis. It could play an
      important role in the pathogenesis of estrogen-dependent breast cancer. The
      aromatase gene consists of at least six exons 1, each containing a promoter, and
      the tissue-specific expression is regulated by alternative use of these multiple
      promoters. The expression of aromatase in the breast and abdominal adipose
      tissues is regulated by a promoter flanking exon 1b. Molecular and
      epidemiological analyses of tissue-specific utilization of multiple exons 1 and
      promoters revealed a switching from use of the adipose-specific exon 1b to exon
      1c in adipose tissues adjacent to the carcinomas in most breast cancer patients.
      Exon 1c has been shown to be specific for the ovary. Aromatase mRNA in adipose
      tissues distal to the tumour of the same patients was normally transcribed from
      exon 1b as was breast tissue in healthy controls. It is noteworthy that a
      switching from exon 1b to exon 1c was often observed in breast cancer patients
      having metastatic lymph nodes. These data suggest that switching from an adipose
      specific exon 1b to exon 1c could cause a deviation from strict regulation of
      tissue-specific expression of the adipose aromatase leading to over-expression of
      the adipose aromatase. Consequently overproduction of local estrogen may promote
      carcinogenesis or proliferation of breast cancer cells.

PMID- 7581493
TI  - Genetic polymorphisms of drug-metabolizing enzymes and lung cancer
      susceptibility.
AB  - A close association of smoking-associated lung cancer incidence with the Msp 1
      and 1le-Val polymorphisms of CYP1A1 gene was found in a Japanese population in
      terms of genotype frequency comparison and cigarette dose response. A synergistic
      increase in susceptibility to lung cancer was observed when the susceptible
      genotypes of CYP1A1 were combined with a deficient GSTM1 genotype. Individual
      difference in expression levels of Ahr and Arnt mRNAs was observed, and the
      expression levels of CYP1A1 appeared to associate with those of transcriptional
      factors. The Ahr protein has two different structures, ascribed to one amino acid
      replacement at codon 554 of Arg by Lys. However, this germ line polymorphism did
      not show a significant association with AHH inducibility nor lung cancer
      incidence. The p53 gene alterations in lung cancer tissues were more frequently
      observed among the patients with a susceptible allele of CYP1A1 gene.

PMID- 7581492
TI  - Polymorphic drug metabolism: studies with recombinant Chinese hamster cells and
      analyses in human populations.
AB  - Most promutagens and procarcinogens exert their genotoxicity after undergoing
      metabolic activation. Metabolism of chemicals is an important factor in limiting
      the extent of the action of a chemical. In this study, we established cell lines
      which carried cDNAs coding for human CYP1A2 and N-acetyltransferase (NAT); the
      latter functions as O-acetyltransferase for N-hydroxyarylamines formed by CYP1A2.
      A cell line which expresses CYP1A2 together with P450 reductase activated
      aflatoxin B1, but not heterocyclic amines. A cell line which carries CYP1A2 and
      polymorphic NAT (NAT2) in addition to P450 reductase efficiently activated IQ and
      some other heterocyclic amines. However, a cell line which carries CYP1A2 and
      monomorphic NAT (NAT1) had only low activity toward the same heterocyclic amines.
      In order to determine the presence of and frequency of genetic polymorphisms of
      CYP1A2 and NAT2 in humans, we performed in caffeine phenotyping test on 205
      Japanese volunteers. Analyses of metabolic ratios of urinary metabolites showed a
      bimodal distribution, indicating that about 86% and 91% of Japanese were
      extensive metabolizers (EM) of CYP1A2 and NAT2, respectively. The genotype NAT2
      determined by the PCR-RFLP method agreed completely with the phenotype. To
      determine the mechanism of the differences in CYP1A2 activity, genomic DNA from
      peripheral lymphocytes of poor metabolizers (PM) and EM was subjected to DNA
      sequencing. No differences in nucleotide sequence were observed between PMs and
      EMs in the exons, exon-intron junctions and 5'-flanking region of the CYP1A2
      gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581494
TI  - Distribution of GSTM1 null genotype in relation to gender, age and smoking status
      in Japanese lung cancer patients.
AB  - GSTM1 gene deficiency has been shown to occur in approximately half of the
      populations of various ethnic origins and has been implicated as a factor for
      elevated risk for lung cancers. However the results have been variable or even
      conflicting between the studies. In an attempt to explore the reason for such a
      diversity, we studied the distribution of GSTM1 genotypes in relation to gender,
      age and smoking status in 447 Japanese lung cancer patients and 469 community
      controls. We found: (1) that in squamous and small cell carcinomas GSTM1 null
      genotype distributed markedly more in females than males especially among the
      patients aged < 70 years (male 57.4%, female 100.0%); (2) that GSTM1 null
      genotype distributed generally more in patients aged < 70 years (58.3%) than
      those aged > or = 70 years (50.0%) irrespective of histologies except for small
      cell carcinoma; and (3) that proportion of GSTM1 null genotype increased
      dependent on the extent of tobacco smoke exposure in male patients having
      squamous and small cell carcinomas aged < 70 years, and remained high but
      independent of the smoking index in adenocarcinoma and unchanged in never- or
      exsmokers from the control level (48.6%). The present study thus suggests that
      composition of GSTM1 genotypes in patients is significantly affected by gender,
      age and smoking status, which should be taken into consideration in any attempt
      to determine the association of GSTM1 genotypes for risk assessment. With the
      diverse of GSTM1 null genotype variability between patients of different
      histologies, our results were also suggestive of different carcinogenic
      involvement of GSTM1 deficiency among different histological cell types.

PMID- 7581495
TI  - Induction of cytochrome P450 isoforms by carcinogenic aromatic amines and
      carcinogenic susceptibility of rodent animals.
AB  - Hepatocarcinogenic aromatic amines such as 4-aminoazobenzene derivatives and
      heterocyclic aromatic amines of cooked food origin were found to be liver
      selective cytochrome P450IAZ (CYP1A2) inducers. Each aromatic amine showed
      different species-specificity among rodent experimental animals in terms of the
      extent of P450 induction. Carcinogenic susceptibility of an animal to the amine
      was well correlated with the activity and/or inducibility of CYP1A2 in the
      animals in the early initiation phase of the carcinogenesis. In hyperplastic
      nodules of rat liver, expression and induction of CYP1A2 as suppressed,
      especially in the placental form of glutathione S-transferase-positive foci.
      Despite the decrease of P450s including CYP1A2 in the rat liver bearing
      hyperplastic nodules. DNA adducts formed by a carcinogenic aromatic amine
      increased, as compared to the controls, suggesting that the activity of DNA
      repair enzyme(s) for the amine-derived DNA adducts might decrease in the
      hyperplastic nodules of rat liver. Treatment of rats with lead nitrate revealed a
      pattern of P450 expression in the liver similar to that observed with rats
      bearing hyperplastic nodules. These findings may provide valuable information on
      the roles of P450s in carcinogenic susceptibility of animals to aromatic amines
      and in the carcinogenic process.

PMID- 7581497
TI  - Cytochrome P450 mediated reactions studied in genetically engineered V79 Chinese
      hamster cells.
AB  - V79 Chinese hamster cells genetically engineered for stable expression of rat and
      human CYP have been shown to serve as analytical tools for studying metabolism
      related problems in toxicology and pharmacology. Here, the application of rat and
      human CYP1A1 and CYP1A2 is demonstrated for comparative studies on the oxidation
      of polycyclic aromatic hydrocarbons, such as phenanthrene, benz[a]anthracene, and
      benzo[a]pyrene. Live cells were cultivated for 2 days in the presence of these
      chemicals. Thereafter, the supernatant medium was checked for metabolites by gas
      chromatography and mass spectrometry. Marked cytochromes P450 and species
      dependent differences in the metabolite profiles were observed. Most important
      was the finding, that human cytochrome P450 1A1 almost exclusively oxidized
      benzo[a]pyrene in the 7,8,9,10-position, yielding the ultimate carcinogen 7,8
      dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene whereas the rat
      cytochrome P450 1A1 oxidized benzo[]pyrene in the 4,5-position and 7,8,9,10
      position. The importance of this finding is underlined by results from
      cytotoxicity studies. Benzo[a]pyrene was twice as cytotoxic in the human
      cytochrome P450 1A1 than in the rat cytochrome P450 1A1 expressing V79 cells.
      Species and cytochrome P450 specific metabolite profiles were also observed for
      phenanthrene and benz[a]anthracene.

PMID- 7581496
TI  - Metabolic polymorphism affecting DNA binding and excretion of carcinogens in
      humans.
AB  - A case-control study on lung cancer patients demonstrated the pronounced effect
      of tobacco smoke on pulmonary carcinogen metabolism and suggested the existence
      of a metabolic phenotype at higher risk for tobacco-associated lung cancer. Lung
      cancer patients who were recent smokers showed in their lungs (i) significantly
      induced CYP1A1-related enzyme activity vs smoking non-lung cancer patients; (ii)
      increased benzo(a)pyrene (BP) tetrol formation from BP 7,8-diol by lung
      microsomes; and (iii) high levels of cytochrome P4501a1 by immunohistochemical
      staining. Levels of bulky aromatic DNA adducts (by 32P-postlabelling) and of BP
      diol-epoxide (BPDE) adducts (by HPC/fluorometry) were quantified in lung
      parenchyma. Aryl hydrocarbon hydroxylase activity and the level of BPDE-DNA
      adducts (r = 0.91; p < 0.001) and to a lesser degree bulky DNA adducts were
      correlated. Thus pulmonary CYP1A1 expression (inducibility) controls in part
      polycyclic aromatic hydrocarbon-DNA adduct formation in tobacco smokers and,
      therefore, appears to be associated with lung cancer risk. High risk subjects for
      lung cancer among smokers may be identifiable through genotyping for polymorphic
      drug metabolizing enzymes in combination with molecular dosimetry of carcinogen
      DNA adducts and mutation analysis in target (surrogate) cells. Such studies in a
      Finnish cohort of lung cancer patients and controls are in progress. Interim
      results of the effect of metabolic polymorphism on the level of PAH-DNA adducts
      and on the excretion of mutagens in urine are summarized.

PMID- 7581499
TI  - [Hot flushes in men after surgical or pharmacologic castration].
AB  - Hormone therapy for prostate cancer is associated with a number of adverse
      effects including hot flushes, which constitute a significant problem as they
      sometimes interfere with everyday life. Every effort must be made to relieve
      patients complaining of this symptom. Several different therapeutic modalities
      are proposed.

PMID- 7581500
TI  - [The importance and significance of post-micturitional bladder residue in the
      evaluation of prostatism].
AB  - The presence of a significant post-voiding residue is often considered to be
      secondary to bladder neck obstruction and frequently constitutes the main
      indication for transurethral resection of the prostate. In order to validate this
      approach, the files of 350 patients presenting with symptoms of prostatism and
      assessed by urodynamic studies were analysed retrospectively. The results of the
      study demonstrated that, regardless of the value of the residue, approximately
      30% of patients were not obstructed despite a high post-voiding residue (PVR),
      while approximately 70% of patients with minimal or no PVR were considered to be
      obstructed on the basis of urodynamic criteria. These results therefore
      demonstrate that the presence of a post-voiding residue is not indicative of
      bladder neck, but reflects a lesion of the detrusor. Considered alone, it
      therefore should not constitute an indication for transurethral resection of the
      prostate.

PMID- 7581498
TI  - The procarcinogen hypothesis for bladder cancer: activities of individual drug
      metabolizing enzymes as risk factors.
AB  - Bladder cancer provides the most definitive example for an association between
      environmental agents and cancer. However, in the absence of industrial
      occupational exposure, the primary carcinogen is rarely identified, and the
      mechanisms involved in cancer formation are poorly understood. The environmental
      procarcinogen hypothesis of tumour pathogenesis proposes that many carcinogens
      require metabolic activation by drug metabolizing enzymes to form the proximate
      carcinogen. A balance of exposure to the carcinogen, the activity of the enzymes
      involved in either formation of proximate carcinogen, or production of non-toxic
      metabolites, will determine tumour risk. We have used mephenytoin, debrisoquine
      and dapsone as selective probes for the phenotypic measures of activity of
      CYP2C19, CYP2D6, and CYP3A4, respectively. Within subject reproducibility of
      phenotypic measures, and the lack of cross-inhibition when the three drugs are
      given in a concurrent cocktail, have been confirmed. We have applied the cocktail
      drug approach in two, non-overlapping series of cases with bladder cancer and
      matched controls. In both series, patients with aggressive bladder cancer (GIII
      histopathology) had a history of excess alcohol intake, an under-representation
      of poor metabolizers of debrisoquine, a significant mean reduction in dapsone
      recovery ratio, but no difference in mephenytoin phenotype. Collectively, these
      observations involving multiple routes of drug metabolism support the
      procarcinogen environmental hypothesis for bladder cancer and suggest that
      measurement of activity of selected individual drug metabolizing enzymes involved
      in the pathogenesis of this tumour can be used to identify subjects at high risk
      of developing bladder cancer.

PMID- 7581501
TI  - [The frequency of surgery of benign prostatic hypertrophy].
AB  - OBJECTIVES: To calculate the incidence of surgical treatment of benign prostatic
      hyperplasia (BPH) in two French departments, Indre-et-Loire and C her, in order
      to deduce the incidence in France. METHODS: All patients operated for BPH by
      transurethral resection or transvesical prostatectomy were counted prospectively
      over a 6-month period by all surgeons of the Indre-et-Loire and Cher departments.
      Collection of case files was complete and based on BPH resection specimens sent
      to pathology. 506 patients were included in this survey. RESULTS: The mean age of
      the patients was 71.8 years. 78% of patients were operated by a private
      urologist, and 93% by a specialist urologist. The mean postoperative stay was 7.1
      days and varied according to the patient's age, the weight of the prostate and
      the site of the operation (university hospital, private establishment and general
      hospital). This study allowed calculation of the annual incidence of surgery for
      BPH in these 2 departments: 822/100,000 men over the age of 50 years. The maximal
      incidence was observed during the 7th decade of life: 1,742/100,000. In our
      study, private urologists operated 76 patients for BPH per year. CONCLUSION:
      Extrapolation of these results to the French population indicates an annual
      incidence of surgery for benign prostatic hyperplasia in France of 776/100,000
      men over the age of 50 years. On the basis of this incidence, an estimated 55,000
      to 65,000 men are operated for BPH per year in France.

PMID- 7581503
TI  - [The annual national epidemiologic survey of tumors of the kidney (April 1993
      March 1994: 970 patients). The Committee of Oncology of the French Society of
      Urology].
AB  - OBJECTIVE: Annual national epidemiological evaluation of renal tumours by means
      of a multicentre survey proposed by the oncology committee of the Association
      Francaise d'Urologie. PATIENTS AND METHODS: From April 1, 1993 to March 31, 1994,
      970 patients were recruited by 54 centres. A computer form was completed for each
      patient, including: the patient's age and sex, modalities of discovery of the
      tumour, complementary investigations (radiological and laboratory tests)
      performed, treatment performed, TNM staging, histological characteristics of the
      tumour. RESULTS: The mean age of the patients was 62.1 years with a sex ratio of
      2 males to 1 female. The rate of incidental tumours was 40%. Radical nephrectomy
      was performed in 90% of cases and conservative surgery was performed in 7% of
      cases. Medical treatment was instituted in 5% of cases. The distribution of
      tumours by TNM stage was: pT1: 8%, pT2: 53%, pT3a: 21% and pT3b: 18%. Lymph node
      involvement was detected in 12% of cases, and visceral metastases were identified
      in 6% of cases. 80% of incidental tumours were intracapsular. The predominant
      histological type was renal cell carcinoma (66%). The mean tumour size for the
      entire series of tumours was 6.4 +/- 3.5 cm and was significantly larger in
      symptomatic patients and in those with poor prognostic factors (adrenal
      involvement, inferior vena cava invasion, lymph node and/or visceral
      involvement). Adrenal and inferior vena cava involvement was detected in 4% of
      cases. 14% of patients had multifocal tumours, which was not correlated with
      either the size of the tumour or the cell type. The nuclear grade was determined
      in 66% of cases and was significantly correlated with perirenal fat and lymph
      node involvement. CONCLUSION: This survey collected approximately 1/5 of all new
      annual cases of renal cell carcinoma in France and therefore provided a precise
      evaluation of the current epidemiology of this tumour.

PMID- 7581502
TI  - [Treatment using concomitant radiochemotherapy of N+ M0 stage urothelial tumors
      of the bladder].
AB  - Seventeen patients with N+ urothelial bladder tumours were treated by a
      combination of deep endoscopic resection and concomitant radiochemotherapy (5FU
      cisplatin). 15 patients completed their course of treatment. 52.9% of these 17
      patients are in complete remission at 6 months, 35.2% are in complete remission
      at 1 year, 30% of patients in complete remission developed distant metastases,
      52.9% developed local progression and 40% developed distant metastases. This
      protocol of deep resection combined with radiochemotherapy can therefore be
      effective in the local control of the tumour and can allow preservation of the
      bladder in the case of complete remission. However, it is insufficient to prevent
      the development of distant metastases. It is therefore preferable to intensify
      this treatment by performing complete endoscopic resection, by increasing the
      radiotherapy dose rate and by intensifying the chemotherapy protocol.

PMID- 7581504
TI  - [Bilateral tumors of the testis: the role of the diagnosis of carcinoma in situ
      in early detection].
AB  - In a series of 540 patients with testicular germ cell tumors, the diagnosis of
      bilateral tumor was observed nine times. Two patients presented a simultaneous
      bilateral tumor and for seven others a second tumor occurred after an interval
      varying from 1 to 16 years. The often late discovery of the contralateral cancer
      sometimes requires a prolonged follow up for patients with unilateral testicular
      malignancy. Incidence, risk factors and therapy are discussed, in particular the
      anomalies in testicular migration, hypofertility, testicular atrophy and
      carcinoma in situ. Prevention of bilateral consecutive tumors depends on the
      research of carcinoma in situ thanks to testicular biopsy. A slight radiotherapy
      allows eradication of this tumor, whose evolution towards invading cancer is
      particularly high. A rigorous watch of these patients can be considered. With the
      absence of early detection, the treatment of the simultaneous tumor needs taking
      into consideration the treatment of the initial tumor. In case of a diagnosis at
      stage 1, observation after orchidectomy is possible without further treatment.

PMID- 7581505
TI  - [The value of biopsy of the inguinal lymph nodes in patients with epidermoid
      carcinoma of the penis].
AB  - Twenty-four inguinal biopsies were performed in 16 patients with invasive
      squamous cell carcinoma of the penis. All patients had suspicion of inguinal
      metastatic involvement. Five patients (31.25%) had inguinal lymph nodes involved
      with tumor. Among 11 patients with negative biopsies, 8 were evaluated during
      careful follow-up. Only 3 patients remained free of tumor at 57.61 and 80 months
      respectively after negative biopsy.

PMID- 7581507
TI  - [Urethroplasty in 2 stages using skin grafts].
AB  - OBJECTIVE: To present the technique and results of 2-stage mesh-graft
      urethroplasty, as described by Schreiter in 1984. METHODS: 11 patients with a
      stricture of the anterior urethra were treated according to this urethroplasty
      (pedicle skin flap). The site of the stricture was penile in 4 cases and
      perineoscrotal in 7 cases, and the mean length was 7.7 cm (range: 3 to 12.5).
      RESULTS: 10 patients were treated in 2 stages, while the remaining patient has a
      persistent perineal urethrostomy. With a mean follow-up of 3.5 years (range: 14
      to 77 months), 9 patients obtained a satisfactory result with no radiographic
      recurrence, but with persistent nocturia (x 2/night), a mean peak flow rate of
      12.8 ml/s, and a mean residual urine of 55 ml present in 8 our of 9 cases. One
      complete failure was observed, following complete recurrence of the stricture due
      to the limited dimensions of the skin flap at the 2nd stage. CONCLUSION: This
      technique constitutes a useful salvage solution after failure of a one-stage
      urethroplasty. It can be used to treat extensive strictures of the anterior
      urethra by reconstituting a good quality urethral lumen with well vascularized
      tissue. It also has the advantage of avoiding the presence of hair follicles and
      allows the two stages to be performed at a brief interval.

PMID- 7581506
TI  - [Ureteroscopy under local anesthesia with or without intravenous analgesia].
AB  - We report our experience on performing ureteroscopic procedures using local
      anaesthesia with or without intravenous analgesia. During a two year period 334
      ureteroscopic procedures were performed in our hospital. 159 of them were begun
      but only 138 completed without the use of general or regional anaesthesia. In 9
      patients ureteroscopy was performed with lindocaine jelly in the urethra only,
      and in 129 with additional intravenous analgesia Fentanyl, a synthetic morphine
      derivative, was used for intravenous analgesia. Ureteroscopy was performed for
      stone fragmentation or extraction in 119 patients for taking away a double J
      catheter which showed migration into ureter in 8 and for diagnostic purposes in
      11. Ureteric lesions were observed in 7 patients (5%). The findings suggest that
      ureteroscopy when performed without general or regional anaesthesia does not
      increase the risk of complications or compromise the results of treatment.

PMID- 7581508
TI  - [The therapeutic aspects of urogenital tuberculosis. Apropos of 86 cases].
AB  - On the basis of a series of 86 cases of urogenital tuberculosis and a review of
      literature, a detailed study of the different therapeutic methods of this
      affection is done. Today, with the tuberculostatic agents, the medical treatment
      alone is frequently sufficient and ablative surgery is less often mandatory than
      reconstructive. Different types of short course chemotherapy and the role of
      associated steroids are reviewed. Finally, the authors stress the indications of
      ablative surgery and review the different procedures of reconstructive surgery in
      order to clearly define a logical therapeutic approach.

PMID- 7581509
TI  - [A simple alternative technic in the treatment of idiopathic hydrocele in adults:
      vaginal "fenestration"].
AB  - The author describes a new, simple technique for the treatment of idiopathic
      hydrocele according to a "fenestration" procedure designed to correct the
      imbalance of intravaginal hydrostatic exchanges. The operation consists of
      initially hemming separately the deep fibrous layer and the parietal leaflet of
      the tunica vaginalis to form the margins of the "window", which is then applied
      by its fibrous layer to the dartos, continuous with the subcutaneous connective
      tissue, a site of rich lymphatic drainage. In a series of 108 patients treated by
      this technique since September 1982, with a follow-up of 6 years, the anatomical
      and functional results were excellent in 98 cases (90.7%), moderate in 6 cases
      (5.5%) and poor in 4 cases (3.7%). Compared to classical techniques, the
      fenestrated opening of the tunica vaginalis with preservation of the tunica
      vaginalis and limited opening of the serosa, preserves the testicular support and
      the protective role of the serosa on the testis. Lastly, suture of the margins of
      the window to the dartos, by facilitating deep lymphatic drainage towards the
      superficial connective tissue, reconstitutes a physiological equilibrium in the
      constant exchanges of intravaginal serous fluids. Experience has demonstrated the
      anatomical and functional efficacy and reliability of this extremely simple
      procedure, which is essentially indicated in adult patients with idiopathic
      hydrocele and a healthy tunica vaginalis.

PMID- 7581510
TI  - [Angiomyolipoma: the role of puncture-aspiration cytodiagnosis].
AB  - Angiomyolipomas (AML) of the kidney are benign tumors easily identified on image
      studies due to their fat content, but differential diagnosis with renal cell
      carcinoma may be sometimes difficult. A case of AML with atypical CT feature that
      were cleared by the characteristic findings on aspiration biopsy cytology is
      described, and the recent literature concerning controversies of image diagnosis
      and usefulness of aspiration biopsy cytology of renal AML is discussed.

PMID- 7581511
TI  - [Transitional cell carcinoma of the ureter and cyclophosphamide: apropos of a
      case].
AB  - The authors present a case of transitional cell carcinoma of the ureter in a
      patient treated by cyclophosphamide-based chemotherapy and radiotherapy for
      Hodgkin's disease. In the light of this case, they review the eight previously
      reported cases of cyclophosphamide-induced ureteric tumours.

PMID- 7581513
TI  - [Bilateral testicular ischemia in vasculitis. Differential diagnosis with torsion
      and the value of color Doppler ultrasonography].
AB  - The authors report a case of acute bilateral testicular pain simulating
      simultaneous bilateral torsion of the spermatic cord in a 22-year-old man. Duplex
      ultrasound revealed parenchymal ischaemia secondary to an early form of
      polyarteritis nodosa (PAN). Surgery, performed because of the doubtful
      differential diagnosis with torsion of the spermatic cord, excluded this
      hypothesis. The aetiological investigation, after excluding an infectious cause,
      consisted of revealing at least three diagnostic criteria necessary for the
      diagnosis of PAN among those defined by Godeau Guillevin or the American College
      of Rheumatology. The authors also discuss the value of duplex ultrasound in the
      follow-up of this disease.

PMID- 7581512
TI  - [Bladder retraction, a complication of chemoprophylaxis of superficial bladder
      cancer using intravesical mitomycin C. Apropos of a case and review of the
      literature].
AB  - Bladder retraction is a rare complication of contact chemotherapy with mitomycin
      C in the treatment of superficial bladder cancer. The clinical and histological
      features and pathophysiology of this lesion are discussed in the light of a
      recent case.

PMID- 7581514
TI  - [Ureteral involvement in an inflammatory aneurysm of the abdominal aorta.
      (Apropos of a case. Review of the literature)].
AB  - Diagnosis and treatment of ureteral obstruction secondary to perianeurysmal
      retroperitoneal fibrosis are controversial. Diagnosis includes the use of
      computed tomography and abdominal ultrasound, surgical treatment combines
      prosthetic graft with preoperative ureteral stenting. Ureterolysis is not always
      necessary, because aneurysm repair promotes resolution of the inflammatory
      process and relieves the ureteric obstruction. However radiologic survey is
      essential as in the case report.

PMID- 7581515
TI  - [Principles, technics and indications of endopyelotomy].

PMID- 7581516
TI  - Transgenesis in mice by cytoplasmic injection of polylysine/DNA mixtures.
AB  - Pronuclear injection is currently the most often used method to make transgenic
      animals, but in some animal species it is temporally restrictive due to
      difficulty in visualizing pronuclei. However, the injection of construct DNA into
      the cytoplasm does not result in transgenesis. The production of transgenic mice
      by a cytoplasmic microinjection technique of polylysine complexed DNA into
      pronuclear stage zygotes is described. Transgenic mice were produced from
      cytoplasmic microinjection of mixtures of a 5.3 kb linearized DNA and poly-L
      lysine (degree of polymerization = 51). Effects on transgenic frequency of both
      the lysine to phosphate ratio of polylysine to DNA and DNA concentration were
      studied. About 12.8% of the pups born from zygotes cytoplasmically microinjected
      with a polylysine/DNA mixture having a lysine to phosphate ratio (L:P) of 1:1 at
      a DNA concentration of 50 micrograms ml-1 were transgenic. The transgenic
      frequency for the pronuclear microinjection positive control of DNA alone was
      21.7%. No transgenic pups were born from microinjection of DNA alone into the
      cytoplasm. Complexes of polylysine/DNA were detected using agarose gel
      electrophoresis at the conditions which produced transgenic mice. The presence of
      polylysine with construct DNA altered the in vitro activities of restriction
      endonuclease and DNA ligase on the construct DNA. The production of transgenic
      animals using DNA and polylysine in the absence of any other signal protein
      suggests that a DNA/polylysine complex but not DNA alone can act as a substrate
      for transgenesis from the cytoplasm.

PMID- 7581517
TI  - Germline transmission of exogenous genes in chickens using helper-free ecotropic
      avian leukosis virus-based vectors.
AB  - We have used vectors derived from avian leukosis viruses to transduce exogenous
      genes into early somatic stem cells of chicken embryos. The ecotropic helper cell
      line, Isolde, was used to generate stocks of NL-B vector carrying the Neo(r)
      selectable marker and the Escherichia coli lacZ gene. Microinjection of the NL-B
      vector directly beneath unincubated chicken embryo blastoderms resulted in
      infection of germline stem cells. One of the 16 male birds hatched (6.25%) from
      the injected embryos contained vector DNA sequences in its semen. Vector
      sequences were transmitted to G1 progeny at a frequency of 2.7%. Neo(r) and lacZ
      genes were transcribed in vitro in chicken embryo fibroblast cultures from
      transgenic embryos of the G2 progeny.

PMID- 7581518
TI  - Altered expression after expansion of a v-erbA transgene in transgenic mice.
AB  - Repetitive DNA is known to undergo size variations based on an increase or
      decrease in the number of monomer units. We describe here the spontaneous
      expansion of an experimentally introduced tandem array of repeats in a transgenic
      mouse consisting of the human beta-actin promoter fused to the viral oncogene v
      erbA and an SV40 polyadenylation signal (hAP/v-erbA). The expansion of the
      transgene was identified during routine screening of transgenic offspring for
      heterozygosity or homozygosity in one founder line. The control heterozygote
      genome consisted of the hAP/v-erbA transgene organized as a tandem array
      approximately five monomer units at a single chromosomal locus. The number of
      units increased to 20-21 copies, and germline transmission of the expanded units
      was stable for at least two generations. The majority of animals carrying the
      expanded monomer units retained their RNA expression patterns; however, some of
      these animals had drastically reduced expression levels. We discuss the
      possibility that expansion of repeated units may provide a mechanism by which the
      expression of a deleterious transgene is reduced.

PMID- 7581519
TI  - Evaluation in tobacco of the organ specificity and strength of the rolD promoter,
      domain A of the 35S promoter and the 35S2 promoter.
AB  - In order to study the expression in plants of the rolD promoter of Agrobacterium
      rhizogenes, we have constructed chimaeric genes placing the coding region of the
      gusA (uidA) marker gene under control of two rolD promoter fragments of different
      length. Similar results were obtained with both genes. Expression studies were
      carried out in transformed R1 progeny plants. In mature transformed tobacco
      plants, the rolD-gus genes were expressed strongly in roots, and to much lower
      levels in stems and leaves. This pattern of expression was transmitted to
      progeny, though the ratio of the level of expression in roots relative to that in
      leaves was much lower in young seedlings. The degree of root specificity in rolD
      gus transformants was less than that of a gene constructed with domain A of the
      CaMV 35S promoter, domA-gus, but the level of root expression was much higher
      than with the latter gene. However, the level of expression of the rolD-gus genes
      was less than that of a gus gene with a 35S promoter with doubled domain B, 35S2
      gus. The rolD-gus genes had a distinctive pattern of expression in roots,
      compared to that of the two other genes, with the strongest GUS activity observed
      in the root elongation zone and in vascular tissue, and much less in the root
      apex.

PMID- 7581521
TI  - [Multicenter clinical study of the effects of once daily administration of
      mepartricin 150.000 U. in benign prostatic hypertrophy].
AB  - The effects of partricin methyl ester, administered to 481 BPH patients at the
      dose of 150.000 U as a single administration at night for 90 days were studied in
      the course of a multicentre study. The favourable evolution of the objective and
      subjective symptomatologic parameters taken into consideration confirmed the
      efficacy of the substance used even by this mode of administration. The size of
      the patient sample ensured that reliable findings were obtained as regards the
      excellent safety of this form of dosage.

PMID- 7581522
TI  - [Our technique in orthotopic neobladder].
AB  - The strive in the field of orthotopic neobladders derives from the need to
      improve their morphofunctional aspects and to simplify the surgical procedures.
      The Authors propose their experience on a new method of orthotopic neobladder in
      8 patients submitted to radical cystectomy for advanced bladder neoplasia from
      march 91 until june 93. The surgical technique was to prepare a reservoir with a
      simile Camey 2 type procedure modified by them using 50 cm of ileus, 30 of which
      detubularized and reconfigured into a simile spheric shape with Polygia 75
      staplers. The remaining length was left intact for the ureteral anastomosis
      performing the Wallace 1 type procedure. The advantages of this technique are
      that: the neobladder is prepared rapidly using staplers, thus reducing operating
      time the presence of an isoperistaltic segment of ileus for ureteral anastomosis
      permits an reduced ureteral mobilization with a low probability of reflux a
      simple reconversion in ileal conduit in case of reservoir failure or neoplastic
      urethral recurrence is possible. The criteria for selecting the patients are
      reported and the diagnostic algorithm regarding the follow-up presented. The
      latter is done with biochemical, echographic, radiological and pressure studies,
      every 4-6 or 12 months. Particular attention has been focused on the quality of
      life in relation to the diurnal/nocturnal continence and micturation interval.
      They conclude that this technique is surgically simple and rapid with
      satisfactory clinical and urodynamic results.

PMID- 7581523
TI  - [Ultrasonography and prostatic adenocarcinoma].
AB  - In the report we refer to our experience as regards the role of transrectal
      ultrasonography in the early diagnosis of prostatic heteroplasia based on the
      results obtained by a research led from January 1991 to January 1995 on 1185
      dysuria patients who have been subjected also to a rectal exploration and a
      serous dosage of PSA. Among the 306/1185 (25.8%) of the patients subjected to
      prostatic echoguided biopsy sec. Hodge in 238 (77.7%) a hypoechogenic zone on
      behalf of the periphery of the prostatic parenchyma has been reported. The
      histological result has pointed out the presence of adenocarcinoma in 81 (26.4%)
      patients; of benign prostatic hypertrophy in 196 (64%); of acute and/or chronic
      non specific phlogosis in 26 patients (8.4%) and granulomatosis prostatitis in 3
      (1%). The sensibility, the specificity and the diagnostic efficiency of the
      transrectal ultrasonography in the diagnosis of prostatic heteroplasia have
      resulted equal, respectively to 100%, to 30.2% and to 48.6%. In 122 patients
      (66%) the hypoechogenic zone was not pathognomonic of prostatic heteroplasia.
      Definitely, considering the high sensibility in opposition to the insufficient
      specificity of the echography, it is our future intention not submit to prostatic
      biopsy those patients who show only a hypoechogenic zone in absence of pathology
      EDR and PSA but to monitor them through quarterly clinic checks.

PMID- 7581520
TI  - An in vivo analysis of transcriptional elements in the mouse alpha-myosin heavy
      chain gene promoter.
AB  - During development in the murine ventricle, there is a switch in myosin heavy
      chain gene (MyHC) transcription. The beta-MyHC is expressed in the ventricles
      during foetal development, but is shut down at or around birth, at which time
      alpha-MyHC transcription is activated. This antithetical switch is thought to be
      mediated by circulating levels of thyroid hormone (TH) and both low and high
      affinity thyroid response elements (TREs) have been identified in the proximal
      promoter region of the murine alpha-MyHC. Myosin gene expression in the atria is
      relatively unaffected by the TH status. Previously, we used site-directed
      mutagenesis of the promoter in a transgenic analysis to define those elements
      responsible for high levels of transcription in vivo. These analyses focused on
      the role(s) of two cis elements, TRE1 and TRE2 that are located at -129 to -149
      and -102 to -120, respectively, on the alpha-MyHC promoter. Although the
      elements' ablation had differential effects on transgene expression, neither
      single mutation abolished transgene expression completely. Here, we show that
      mutating both elements results in a complete inactivation of the transgene in
      both ventricles and atria under euthyroid conditions. However, expression still
      can be detected in the hyperthyroid state, implying that, although the TRE1 and
      TRE2 elements are critical elements for high levels of alpha-MyHC transcription
      in vivo, other promoter sites can mediate at least some degree of transcriptional
      activation.

PMID- 7581524
TI  - Infections after renal transplantation. Recipient factors affecting their
      incidence.
AB  - We have evaluated the incidence of infection in patients with kidney transplant,
      their effect on graft function and on patient outcome. Factors important for the
      development of infections in the post-transplant course in this group of patients
      have been analyzed, as well as factors affecting graft and patient survival. The
      prevention of infection is the main aim in this patient population, as every
      episode of clinical infection requiring treatment carries the potential for
      lethal consequences, and every effort should be made to assure appropriate
      screening of the prospective renal recipient.

PMID- 7581526
TI  - The origin of the modern endoscope.

PMID- 7581525
TI  - Sonourethrography in anterior urethral stricture: comparison to radiographic
      urethrography.
AB  - Twenty-three male patients with known or suspected urethral stricture disease
      were evaluated using sonourethrography and standard retrograde x-ray
      urethrography for comparative analysis of two techniques. Results were evaluated
      statistically. These two methods can substitute each other in determining the
      stricture area length of anterior urethra. Due to advantages, if both of these
      methods are used combining each other, we believe that they will be much more
      sensitive.

PMID- 7581527
TI  - [BCG vs. BCG plus recombinant alpha-interferon 2b in superficial tumors of the
      bladder].
AB  - BCG intravesical instillation is a well established therapy for superficial
      bladder carcinoma as adjuvant and/or prophylactic treatment. However side-effects
      are frequent when full doses are employed and therefore low dose alternative
      schedules were proposed. Interferon intraluminal therapy for bladder TCC has been
      used with similar indication but the results did not encourage further single
      drug trials. A double arm random study, BCG full dose vs. BCG low dose, is
      presented. The results point out that the combination treatment is superior to
      BCG full dose therapy in terms of side effects and similar to BCG full dose as
      regards efficiency (5/18 vs 4/18 recurrences) after a follow-up of 24.11 +/- 8.15
      for BCG and 16.72 +/- 8.7 for BCG + IFN.

PMID- 7581529
TI  - Cytological, histological and ultrastructural findings of a pure benign Sertoli
      cell tumor.
AB  - A pure Sertoli cell tumor of the testis in a 26-year-old man is reported, with
      cytologic, histologic and ultrastructural findings. The preoperative cytological
      diagnosis allowed a conservative surgical approach.

PMID- 7581528
TI  - [Bourneville's syndrome: diagnostic and urologic implications].
AB  - Angiomyolipoma is a rare tumor frequently associated with tuberous sclerosis and
      it has a higher incidence of bilateral renal involvement in this case. Patients
      effected by Bourneville's Syndrome are often more symptomatic than patients with
      angiomyolipoma only, however it is necessary to examine the renal conditions in
      all of them because of the high risk for severe hemorrhage. Diagnostic evaluation
      is based on radiological findings as Ultrasonography and Computed Tomography. We
      present a case of bilateral and symptomatic angiomyolipoma is a young woman with
      Bourneville's Syndrome.

PMID- 7581530
TI  - [Use of stents in postoperative recurrent urethral stenosis].
AB  - We have started study after a publication (1) about our experience on 1376
      urethrotomies executed above 784 patients; the 11% of these stenosis have been
      consequent on endoscopic or open surgery. In the 23% of these patients we have
      made more than two urethrotomies and in 4% of these the endoscopic operation has
      not been resolutive. We described the use of the urethral wall stent in 13
      patients with recurring urethral strictures. The stainless steel stent is self
      expanding when released from its endoscopic introducer. We have desobstructed the
      100% of the patients and obtained a max flow between 15 and 24 ml/sec. We haven't
      had problems of re-epithelialization if excluded two patients where observed a
      stabilized exuberant re-epithelialization without uroflowmetry variations. It is
      considered that this endoscopic technique offers a simple, safe and effective
      alternative to multiple dilatations and urethrotomies in patients with bulbar
      urethral strictures.

PMID- 7581531
TI  - Bilateral renal tumours: a hard surgical problem. Case report.
AB  - Three cases of bilateral renal tumours are reported. A radical nephrectomy in the
      side with the larger tumour and a nephron-sparing surgery (partial nephrectomy or
      enucleo-resection) in kidney with smaller lesions was performed in two cases. A
      bilateral partial nephrectomy was performed in the last patient (tumours larger
      than 5 cm). Two of them performed a needle CT-guided biopsy before surgery, but
      full disagreement was found between pre and post-operative histological results.
      In addition, we outline that a second lesion was found intraoperatively in the
      case n. 3, without any radiological and sonographic finding. We stress the
      importance of a conservative surgery in case of bilateral neoplasms. Only surgery
      could assure a careful staging and histological diagnosis.

PMID- 7581532
TI  - [A case of hemorrhagic complication revealing renal angiomyolipoma].

PMID- 7581533
TI  - [Renal angiomyolipoma with locoregional lymph node localization associated with
      pulmonary tuberous sclerosis: a case report].
AB  - The angiomyolipoma is a rare tumor of the kidney with benign clinical evolution
      which can be found in more than half of the female patients with tuberous
      sclerosis. An uncommon case of renal angiomyolipoma with extracapsular extension,
      inter-aortocaval lymph node involvement and pulmonary lymphangiomyomatosis with a
      clinical history of spontaneous recurrent pneumothorax but without the
      neurological signs of the tuberous sclerosis, is described. The natural history
      of this disease which has various clinical forms of presentations is still
      unclear. The role of the lymph-node dissection in the surgical treatment of this
      tumor is discussed.

PMID- 7581534
TI  - Infectious disease testing for blood transfusions.
AB  - OBJECTIVE: To provide physicians and other transfusion medicine professionals
      with a current consensus on infectious disease testing for blood transfusions.
      PARTICIPANTS: A non-Federal, nonadvocate, 12-member consensus panel representing
      the fields of hematology, infectious disease, transfusion medicine, epidemiology,
      and biostatistics and a public representative. In addition, 23 experts in
      hematology, cardiology, transfusion medicine, infectious disease, and
      epidemiology presented data to the consensus panel and a conference audience of
      450. EVIDENCE: The literature was searched through Medline and an extensive
      bibliography of references was provided to the panel and the conference audience.
      Experts prepared abstracts with relevant citations from the literature.
      Scientific evidence was given precedence over clinical anecdotal experience.
      CONSENSUS: The panel, answering predefined consensus questions, developed their
      conclusions based on the scientific evidence presented in open forum and the
      scientific literature. CONSENSUS STATEMENT: The panel composed a draft statement
      that was read in its entirety and circulated to the experts and the audience for
      comment. Thereafter, the panel resolved conflicting recommendations and released
      a revised statement at the end of the conference. The panel finalized the
      revisions within a few weeks after the conference. CONCLUSIONS: The serum alanine
      aminotransferase test should be discontinued as a surrogate marker for blood
      donors likely to transmit posttransfusion non-A, non-B hepatitis infection since
      specific hepatitis C anti-body testing has eliminated more than 85 percent of
      these cases. Anti-hepatitis B core antigen testing should continue as it may
      prevent some cases of posttransfusion hepatitis B; it also may act as a surrogate
      marker for HIV infection in donors and may prevent a small number of cases of
      transfusion-transmitted HIV infection. Syphilis testing should continue until
      adequate data can determine its effect on the rarity of transfusion-transmitted
      syphilis. Vigilant public health surveillance is critical in responding to
      emerging infectious disease threats to the blood supply.

PMID- 7581535
TI  - [The effect of the intranigral use of the delta sleep-inducing peptide and its
      analogs on the motor and seizure activities of rats].
AB  - The effects of delta-sleep inducing peptide (DSIP) and its analogues (1-4)
      administered into substantia nigra pars reticulata on locomotor and seizure
      activity were estimated in experiments in rats. It was shown that intranigral
      microinjection of DSIP as well as DSIP-1-DSIP-4 caused decreasing of horizontal,
      vertical locomotor activity and attendance of central sectors of the "open
      field". Antiseizure effects, i.e. the first and clonic-tonic picrotoxin-induced
      convulsive latent period lengthening and their intensity decreasing, revealed
      DSIP, DSIP-2 and DSIP-3. Authors suppose that changes of DSIP structure lead to
      changes of effects expression on locomotor and seizure activity in conditions of
      their administration into substantia nigra reticulata. Obtained data concerning
      protective effects of studied peptides on experimental seizure syndrome allow to
      conclude that there is interaction between DSIP-induced hypokinesia and DSIP
      analogues anticonvulsive effectiveness in case of their intranigral
      administration which is likelihood is one of the component of nigral-dependent
      seizure-suppressive mechanism.

PMID- 7581536
TI  - [The pedagogical activities of an academic and scientific complex (on the 20th
      anniversary of the creation of the P. K. Anokhin Research Institute of Normal
      Physiology of the Russian Academy of Medical Sciences)].

PMID- 7581537
TI  - [Serotonin metabolism in different areas of the brain and spinal cord in post
      vibration hypotonia].
AB  - General vertical vibration enhanced the lability of the vascular tone in adult
      male rats. Quite often a decrease in AP occurred in rats with high initial blood
      arterial pressure. The data obtained suggests that the neurochemical mechanisms
      of post-vibration hypotony and the hypotony in control animals are different.

PMID- 7581538
TI  - [Poststress lesions of the gastric mucosa in inbred mice after the peripheral
      administration of cyproheptadine and propranolol].
AB  - Intraperitoneal administration of 5-HT2-receptor blocking agent ciproheptadine
      abolished the protective effect on stress-induced damage of gastric mucosa in
      male mice, while propranolol depresses this protective effect. Propranolol
      prevented a damaging effect of serotonine on gastric mucosa. Consequences of
      emotional stress on gastric mucosa seem to be realised through different types of
      serotoninergic receptors.

PMID- 7581539
TI  - [The effect of postnatal sympathectomy on the production and receptor binding of
      sex steroids in female rats during puberty].
AB  - The total chemical desympathization caused by injection of 6-hydroxydopamine in
      the first day of life increased the progesterone secretion, decreased the
      estradiol secretion and abolished translocation of estradiol receptors to the
      cell nuclei in the uterus of 1-2 days old rats, which correlated with the absence
      of uterus weight increase after exogenous estradiol injections. The peripheral
      desympathization caused by injection of neurotoxin to two weeks old rats induced
      only estradiol secretion decrease, but to the less extent than after total
      desympathization.

PMID- 7581540
TI  - [The evaluation of corticosteroid hormone receptor status in the brain structures
      of stressed and adrenalectomized rats].
AB  - The value of receptor capacity in respect to cytosol concentration was shown to
      vary, therefore two criteria are proposed for estimation of condition of the
      cytosol corticosteroid receptors: the density of the receptors in tissue and the
      range of intermediate (active) complex. The number of receptors in the hypophysis
      was shown to reduce after adrenalectomy whereas in the hypothalamus, hippocampus
      and striatum it increased. The range of intermediate complex was shown to change
      differently in different structures after stress.

PMID- 7581541
TI  - [Stress-induced analgesia. The role of the hormones of the hypophyseal
      adrenocortical system].
AB  - The effect of stress on pain threshold and blood corticosteroids was studied in
      anesthetised rats. The stress stimulation resulted in a parallel changes of
      analgesia and blood corticosteroids. Stress-induced analgesia were decreased
      after blocking of the pituitary-adrenocortical system by means of dexamethasone
      implantation (200 micrograms) in paraventricular nucleus of hypothalamus or i. v.
      administration of hydrocortisone (15 mg/100 g b. w.). Naloxone administration (1,
      10 mg/kg) does not block analgetic effect and corticosteroid level. These results
      suggest that pituitary-adrenocortical axis provide non opioid stress-induced
      analgesia.

PMID- 7581543
TI  - [The effect of neutrophilic secretory products on erythropoiesis in bone marrow
      erythroblastic islands].
AB  - The secretory products of the neutrophils were shown to exert an activating
      effect on the erythropoiesis in case of an activating neutrophil supernatant. The
      latter seems to modify the reactivity of the central macrophages in animals with
      suppressed endogenous erythropoietin.

PMID- 7581542
TI  - [The unknown physiological role of carbon dioxide].
AB  - In rats adapted to hypoxia, in gradual increase of CO and decrease in
      monosialogangliosides, were shown as well as insufficient accumulation of the
      lipid peroxidation products. The data suggests that carbon dioxide is a natural
      element of the organism antioxidant defence system.

PMID- 7581544
TI  - [The heterogeneity of the reaction of plasma renin activity in the arterial blood
      of rats to acetylcholine infusion into the systemic blood flow].
AB  - I.v. administration of acetylcholine in anesthetised rats with a preliminary
      adrenoblockade decreased the plasma renin activity (PRA) of arterial blood in
      rats with an increased sympathetic reactivity and a high sensitivity to
      acetylcholine. The PRA did not change in the rats with a high adrenergic effect
      on the PRA. The data suggests that the PRA response to acetylcholine depends on
      sympatho-parasympathetic interaction.

PMID- 7581545
TI  - [The effect of chronic irradiation with intermittent unmodulated microwaves on
      the functional status of the rabbit].
AB  - A group of 10 chinchilla male rabbits were exposed to 800 MHz alternative
      microwave fields. The data obtained revealed changes in the EEG, ECG and
      respiration in only 2 rabbits after 5-7 experiments.

PMID- 7581547
TI  - [The effect of experimental hyper- and athyroidism on the temperature dependence
      of some physiological reactions].
AB  - Athyroidism decreased (-42%), hyperthyroidism increased (+11%) the level of
      temperature dependence of the heart chronotropic function. The data obtained
      revealed different characteristics of the temperature dependence in white rats in
      different states of the thyroid gland.

PMID- 7581546
TI  - [Changes in the number of alpha 2- and beta-adrenoreceptors in the brain stem and
      cerebral cortex of rats in ontogeny].
AB  - Densities of alpha 2- and beta-adrenoceptors were higher in the brain stem of 21
      day-old foetuses. The beta-receptors density, however, increased more rapidly in
      the brain stem after birth. The alpha 2-adrenergic receptors density gradually
      elevated with ageing in the cortex, the specifics of their ontogenesis being
      related to regulation of noradrenergic nerve cells function while that of the
      beta-adrenoceptors reflected a formation of adrenergic synapses in the brain
      areas in the course of development.

PMID- 7581548
TI  - [The effect of drugs on bronchial patency under conditions of respiratory
      musculature fatigue].
AB  - Against the background of the respiratory muscle fatigue, histaminic
      bronchoconstricting response became sharply aggravated, resulting in death in 82%
      in anesthetized cats. The death could be prevented by a number of agents,
      euphyllinum, pyracetamum and adenosintriphosphoric acid being the most efficient
      at that.

PMID- 7581549
TI  - [Begging and sharing in a group of adolescent chimpanzees].
AB  - 80 15-min tests using toys were carried out with 4 juvenile chimpanzees who, to
      obtain the toys, used 4 strategies: (1) taking by force, (2) snatching and
      fleeing, (3) begging, (4) hysterics. Sharing toys was a normal strategy of high
      ranking animals. Begging and hysterics were mainly used in contacts with the
      latters. A strong negative correlation was found between hysterics and friendly
      behaviour.

PMID- 7581550
TI  - [The efficiency of heat emission from skin vessels with different radii].
AB  - Important heat-physical parameters of the heat release by the blood in different
      vessels, were revealed enabling authors to estimate the effect of the vessel size
      on the heat release from the flowing blood. The skin arterial vessels of 0.05-0.2
      mm radius were found to play the main role in the organism heat exchange with
      ambient environment.

PMID- 7581551
TI  - [A neurophysiological assessment of the effect of trimetidon on brain function in
      the cat].
AB  - Stimulation of the cat brain mesencephalic RF augmented the high-frequency
      activity in control animals and failed to do so after 4-oxopyrimidine
      administration. These and some other EEG changes suggest presence of an
      anxiolytic component in the trimethidone, the latter thus being similar by its
      effect to 1,4-benzodiazepines and endogenous pyrimidines.

PMID- 7581553
TI  - [The chemical stability of enkephalin-like tetrapeptides in a cannula implanted
      in the rat neostriatum for multiple microinjections].

PMID- 7581552
TI  - [The diffusion permeability of the wall of the animal lung for oxygen, carbon
      dioxide, nitrogen and helium].

PMID- 7581554
TI  - [Na(+),K(+)-ATPase activity in the neurons and glial cells of the olfactory
      cortex of the rat brain in the dynamic development of long-term potentiation].
AB  - The initial stationary phase of the LTP was followed by a decrease in the
      Na(+),K(+)-ATPase activity of neurons and an augmentation of enzyme activity in
      the glial cells. Decay of the LTP tends to normalize the above types of activity.

PMID- 7581555
TI  - [A quantitative assessment of the process of the reflection of the spatial
      brightness properties of a stimulus by the neuronal structures in the lateral
      geniculate body of the cat].
AB  - Correlation between spatial brightness distribution in the test image and the
      spatial response distribution was estimated for the cat LGB. The correlation was
      found to be quite high. The data obtained corroborate the hypothesis by Podvigin
      and Kuperman of the topological correspondence of isophote structure family to
      the pattern of activity reflecting the test image.

PMID- 7581556
TI  - [The effect of taftsin on the function of the brain structures in rats with a
      dysfunctioning dopamine system].
AB  - Tuftsin administration enhanced the electrical activity in the visual and motor
      cortex and in the n. caudatus. Against the background of haloperidol. Tuftsin
      normalised activation of the neurotransmitter system. The data obtained suggest
      that the modulated action of peptides to be one of the ways of compensating
      processes developing in pathological situations.

PMID- 7581557
TI  - [The characteristics of the corticosteroid receptors in the hormonal modification
      of the stress reactivity of rats].
AB  - After neonatal administration of hydrocortisone the rat litter preserve
      inhibition of function of the hypophyseal-adrenal system at the age under 2
      months. During the inhibition period, the number of corticosteroid receptors was
      decreased in the hypothalamus and hippocampus and increased in the hypophysis. At
      the 3-month age, binding of corticosteroids in these structures is restored.

PMID- 7581558
TI  - [The effect of the combined action of chronic gamma irradiation and emotional
      stress in rats].
AB  - Combined gamma irradiation and stress increased the emotional response in rats.
      The number of lymphoid cells increased significantly in the bone marrow, thymus
      and spleen, whereas fewer reticulocytes, neutrophils and thrombocytes were found
      in the peripheral blood.

PMID- 7581559
TI  - [Gastric stress ulcers: the protective role of hormones of the hypothalamo
      hypophyseal-adrenocortical system].
AB  - The role of hypothalamo-pituitary-adrenocortical (HPA) axis in stress-induced
      ulceration is reviewed. The special attention is devoted to corticosteroids. It
      is discussed our hypothesis according to which a gastric ulcer formation after
      administration of high corticosteroid doses is due to the insufficiency of
      corticosteroid production as a result of suppression of HPA axis. The evidence
      strongly supports our hypothesis about antiulcerogenic property of
      corticosteroids. Gastric microcirculation, as main subject of antiulcerogenic
      action of glucocorticosteroids, is reviewed. Conclusion derived from the data
      that corticosteroids play defensive role during stress-induced ulceration and
      their action is provided by maintenance of gastric microcirculation.

PMID- 7581560
TI  - [Stress-induced analgesia. The role of corticosteroids].
AB  - Non-opioid stress-induced analgesia was studied in anesthetized rats, which were
      treated with electroshock (0.7 mA, 15 sec on, 15 sec off, 3 min duration)
      delivered through fixed hind limb electrodes. Tail-flick threshold of
      electroshock stimulation of the tail was used as a measure of analgesia. Stress
      induced analgesia was decreased by adrenalectomy. Medullectomy did not block
      analgesic effect of stress. These results suggest that corticosteroids, but not
      enkephalins of adrenal medulla, provide the analgesia induced by short-term
      stress.

PMID- 7581562
TI  - [The role of 5 alpha-dihydrotestosterone in regulating the sexual maturation of
      male rabbits].
AB  - The data obtained suggest a greater sensitivity of the prepubertal rabbits'
      hypophysis for small doses of 5 alpha-dihydrotestosterone exerting an inhibitory
      effect. The data emphasizes the significance of the agent for regulation of
      sexual maturation.

PMID- 7581561
TI  - [The lipolytic enzyme activity of the mitochondrial membranes of the digestive
      organs in heat stress in rats].
AB  - An augmentation of catalytic activity of phospholipase A and lysophospholipase A
      occurred in the liver mitochondria membranes and small intestine mucosa in rats
      subjected to heat. The augmentation of the latter's activity was significantly
      lesser in overheated rats.

PMID- 7581563
TI  - [The effect of stimulation of the orbitofrontal cortex on the activity of the
      bulbar respiratory neurons and on respiration in normal rats and in hypoxia].
AB  - Stimulation of the orbito-frontal cortex inhibited activity of bulbar expiratory,
      inspiratory and reticular (non-respiratory) neurons. The first phase of hypoxia
      generated facilitatory influence of cerebral activating structures, whereas the
      second phase led to a contrary effect (depression). Subcortical activating
      structures, however, retained some of their facilitatory influence thus
      maintaining the oxygen homeostasis of the organism.

PMID- 7581565
TI  - [The effect of experimental hyperthyroidism on the thermoregulating activity of
      the motor units in rat skeletal muscles].
AB  - The T3 thyroid hormone was shown to change the motor unit activity in the
      thermoregulatory tonus from 13 to 22/sec in intact rats to 9 to 11/sec in the
      hyperthyroid ones. This data corresponds to that obtained in rats adapted to cold
      and suggests participation of thyroid hormones in cold adaptation.

PMID- 7581566
TI  - [The morphochemical characteristics of the neurons of the sensorimotor cortex and
      neostriatum in rats with differing degrees of alcohol preference].
AB  - Cytochemical techniques revealed that the content of the cytoplasm albumins and
      the size of the cortex neurons depended on the level of alcohol preference in
      rats. The neurons nucleus' proteins, however, do not depend on the alcohol
      preference and are associated with their cognitive characteristics rather.

PMID- 7581564
TI  - [The influence of 2,4-dinitrophenol on the temperature effect of muscle
      contraction in experimental hyperthyroidism].
AB  - Experimental hyperthyroidism reduced the force of muscle contraction leaving
      unaltered the temperature of the contracting skeletal muscles in rats. The
      thermal effect therefore was increased as per the unit of developing force.
      Administration of 2,4-dinitrophenol increased the temperature effect in intact
      rats and exerted no influence in the hyperthyroid animals.

PMID- 7581567
TI  - [The vagotropic action of kyotorphin in cats].

PMID- 7581568
TI  - [The striatonigral-thalamic mechanisms in the organization of behavior].
AB  - Experiments in dogs with striatal deficiency revealed an important role of
      dopaminergic mechanisms in establishment of the situation conditioning. A
      rearrangement of the background unit activity of the caudate and thalamic nuclei
      preceding presentation of a conditioned stimulus and correlating with correct
      accomplishment of a motor task, was revealed in cats. Afferents from intralaminar
      and ventral nuclei of the thalamus were shown. Participation of striatal, nigral
      and thalamic levels in systemic organisation of motor conditioning is discussed.

PMID- 7581569
TI  - [Psychological and electrophysiological phenomena in pathology of the
      gastrointestinal tract].

PMID- 7581571
TI  - [The effect of age on the genetic correlates of visual evoked potentials in man].

PMID- 7581570
TI  - [Changes in the functional asymmetry of the CNS in children with congenital brain
      pathology during the correction of motor disorders].

PMID- 7581572
TI  - [Model representations of neostriatal function and the activity of its neurons in
      monkey behavior].

PMID- 7581573
TI  - [The physiological mechanisms of the regulation of zoosocial behavior in rats
      exposed to low-frequency electromagnetic fields].
AB  - The infraslow frequency electromagnetic fields were shown to affect social
      activity in rats: the changes induced by territorial priority and isolation were
      eliminated, an interaction between the motor activity and the social status
      appeared. The monoaminergic system of the rat brain seems to take part in
      physiological mechanisms of regulation of the zoosocial behaviour according to
      changes in ambient conditions.

PMID- 7581574
TI  - [The electroencephalographic mapping of the brain biopotentials that precede
      saccadic eye movements in man].

PMID- 7581575
TI  - [The characteristics of the participation of the neostriatal cholinergic system
      in regulating different forms of defensive behavior].
AB  - The effects of microinjections of the cholinergic agonist (carbacholine) into the
      dorsal part of the neostriatum on discrimination processing of sensory signals
      were studied in chronic experiments in dogs (instrumental defensive reflex
      connected with maintenance of flexion posture) and in rats (active avoidance
      learning in T-maze). It was found that an improvement of discrimination process
      after carbacholine injections was manifested as an increase in the number of
      correct responses during acquisition of discriminative avoidance reflex in T-maze
      (rats) and during differentiation of sound signals in instrumental defensive
      reaction (dogs). The efficacy of this influences was suggested to be depend on
      the level of animal learning. We did not shown an improvement of the responses in
      two cases: 1. When before the microinjections the responses on the defensive and
      on the discriminative signals did not distinguish; 2. Under total differentiation
      of signals (e. g. under total learning). In both cases the neostriatum seems to
      be not involved in behavioral reaction what could be accompanied by low neuronal
      activity during the these signals action.

PMID- 7581576
TI  - [The characteristics of endogenous evoked potentials during normal psychomotor
      reactions and during basal ganglionic dysfunction in man].
AB  - Averaged cortical EPs (or the ERPs) in response to light stimuli were analysed in
      the Fz, Pz and Oz leads in healthy subjects and in Parkinsonian patients. The
      largest CNV and Nd (negative difference) were recorded in the Fz, the negative
      waves being inversely related to each other. A delay in psychomotor responses was
      accompanied by a decrease in the endogenous ERPs in all the leads in Parkinsonian
      patients. The ERp attenuation seems to be connected with the cortical
      hypoactivation due to the basal ganglia disfunction.

PMID- 7581578
TI  - [The corollary neuronal activity of the parietal associative cortex in the cat
      during different types of voluntary movements].
AB  - Unit activity of 201 neurons was studies before the EMG activation in the area 5
      in cats trained to perform a stereotypic movement in response to a triggering
      stimulus and without it. The data obtained suggest that the parietal associative
      cortex takes part both in triggering of different voluntary movements and in
      active inhibition of this process.

PMID- 7581577
TI  - [The effect of the destruction of the striate and prestriate cortices on the
      differentiation of visual images in cats].
AB  - The experiments to examine the effects of different visual cortical lesions (area
      17 and 21 of the cat cortex) on the image discrimination were conducted.
      Different image complexity and context of images presentation were established.
      Cats with area 17 lesion easily discriminated simple objects, and learned only
      positive image from context. Cats with area 21 lesion learned all experimental
      conditions. We suggest that intact area 21 carry out selection one object
      context.

PMID- 7581579
TI  - [The effects of the orbital cortex on the neuronal activity of the tegmentum
      mesencephali in a food reflex in cats].
AB  - In chronic experiments on cat influences of functional exclusion of the orbital
      cortex on the rearrangement neuronal activity of the midbrain tegmentum on
      performance of food-acquiring conditioned reflexes have studied. Most neurons
      showed decreased firing rate responses increased latency and increase of number
      short interspike intervals accompanied by changes in parameters of the food
      acquiring responses: increase latent periods and long persistence of
      electromyogram. The above-noted facts have shown that the most obvious excitatory
      influences to the midbrain tegmentum from orbital cortex in the period of
      initiation condition motor response.

PMID- 7581580
TI  - [The function of the hypophyseal-adrenocortical system and the orienting
      exploratory behavior of rat pups].

PMID- 7581582
TI  - [The structural bases for the correction of disordered brain functions by the
      transplantation of dissociated embryonic nerve tissue].

PMID- 7581581
TI  - [Intralimbic evoked potentials and excitatory cycles under conditions of food and
      defensive motivations in dogs].

PMID- 7581583
TI  - [Event-related potentials evoked by conscious and unconscious visual stimuli in
      disorders of sensory input].

PMID- 7581584
TI  - [The role of interoceptive afferentation in regulating motor activity in the
      early postnatal ontogeny of rats].

PMID- 7581585
TI  - Influence of menopause on sexuality.
AB  - Menopause is associated with anatomical, physiological and psychological changes
      that often influence sexuality in the aging female. The decreased estrogen levels
      have a multitude of effects on sexual function, including decreased support of
      female pelvis, loss of ability to adequately lubricate the urogenital tissue, and
      changes in body configuration. This situation is aggravated by the alterations in
      the skin, breasts, muscles and skeleton caused by estrogen loss. For many women,
      these changes translate into a poorer self-image, diminution of self-esteem and,
      eventually, a loss of sexual desire. Societal expectations also have a negative
      impact on sexuality, as most cultures still believe that older women become
      sexually retired. Although this attitude is changing, cross-sectional studies
      still show that there are negative sexuality changes associated with menopause
      and that postmenopausal women note a loss of sexual desire. Age and relationship
      status are also important correlates of sexual activity and sexual satisfaction.
      With increasing age, the frequency of most types of sexual activity decreases and
      sexual dysfunctions increase. Urogenital atrophy due to loss of estrogen is one
      of the most important contributors to the decline in sexual activity with the
      menopause. Partner availability and partner function are important contributors
      as well to the decline of sexual activity, since older men, like older women,
      often have sexual dysfunctions. Overall, decreased sexual desire and loss of
      vaginal lubrication in the female and erectile difficulties in the male, or
      absence of a partner, are commonly reported causes of increasing sexual
      difficulties for the older female. Hormone replacement therapy not only
      ameliorates the local anatomic and physiologic changes, but also may have
      positive psychological benefits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581586
TI  - Compliance to hormone replacement therapy.
AB  - Hormone replacement therapy (HRT) after menopause can effectively reduce
      climacteric-related symptoms and therefore increase quality of life. A large
      number of studies have also demonstrated that with a sufficient dosage bone loss
      can be prevented and fracture frequency reduced. Epidemiological and experimental
      studies also suggest a decrease in cardiovascular mortality and morbidity among
      HRT users compared to nonusers. From an epidemiological perspective, in order to
      obtain optimal prevention of osteoporosis and of cardiovascular diseases, a high
      proportion of postmenopausal women should be treated using long-term therapy.
      Surveys generally show that only a small proportion of postmenopausal women use
      hormone replacement therapy (in Belgium, around 14%) and that the long-term
      compliance to treatment, which is mandatory in the prevention due to low
      compliance remains unknown. The reasons why patients patients do not pursue their
      treatment in the long run remain unclear. Fear of cancer and drug-related side
      effects, such as unacceptable bleeding, have been among the most frequently
      mentioned causes. Thus, individual information on patients regarding HRT seems to
      be crucial issue. A few recent studies have suggested a favorable role of
      osteoporosis prevention and bone mass measurements to increase compliance, but
      this is not well established and will depend on the physician's attitude toward
      HTR and osteoporosis prevention. At present, very little is known about the
      physician's decision to treat postmenopausal women with HRT. Sometimes, the
      physician's attitude has been reported was very negative toward HRT-apparently,
      many physicians think HRT increases cardiovascular risk, even though most data
      suggest a reduction of cardiovascular risk among HRT users. Very little research
      has actually been performed on how to improve compliance. Education and
      behavioral strategies may be of use. Improved communication between patients and
      physicians, establishing a confidential relationship with patients, and the
      involvement of nursing counseling are all strategies which may improve
      compliance. The use of easy-to-take medication that induces no bleeding,
      supported by calendar devices or reminders, may facilitate chronic use of
      medication. Future research needs to investigate the physician's and patient's
      decision-making processes and the reasons for those decisions.

PMID- 7581587
TI  - Is HRT indicated for the prevention of cardiovascular disease?
AB  - There is compelling evidence to suggest that estrogen administration to women of
      climacteric age reduces subsequent myocardial infarction by some 50%.
      Accumulating data also suggests estrogens confer substantial protection from
      stroke. Given this rationale, it is prudent to suggest to regulatory bodies that
      estrogen treatment would have this indication. Estrogens have other well-defined,
      and less well-defined, effects on various diseases; but observational studies
      suggest a decrease also in the overall mortality in estrogen users compared to
      nonusers. The critique of this concept is mainly that there is but one small
      clinical trial, and that observational data may be subject to confounders and
      biases. Questions have been raised whether the estrogen user comes from a
      preselected healthier population. Several of the observational studies are large
      enough to control for preexisting morbidity, including risk factors of
      cardiovascular disease. If anything, it would seem that women carrying risk
      factors inclusive of a sustained myocardial infarction are even better off
      (yielding a relative risk of 0.2) than those without risk factors. In order to
      protect the endometrium from malignant transformation and to ensure an acceptable
      bleeding pattern, a progestogen co-medication must be given with the estrogen.
      Observational data are based almost exclusively on estrogen-alone preparations,
      and concern has been expressed that progestogen addition may attenuate or even
      eliminate cardioprotection. Different estrogens at different doses, with
      different modes of administration, may also have an impact in this respect. The
      large variety of existing schedules for the administration of the progestogen
      adds to the difficulty in interpretation of the data with regard to
      cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581588
TI  - Does HRT modify risk of gynecological cancers?
AB  - A substantial body of recent experimental, clinical and epidemiological evidence
      indicates that hormones play a major role in the etiology of several human
      cancers. The ability of hormones to stimulate cell division in certain target
      organs such as the breast, endometrium, prostate and the ovary, may lead
      following repeated cell divisions to accumulation of random genetic errors that
      ultimately produce the neoplastic phenotype. Hormone-related cancers account for
      more than 30% of all newly diagnosed female cancers in the United States. While
      most non-hormone-dependent adult cancers rise continuously with age, hormone
      responsive cancers of the breast, the ovary and the endometrium rise with age
      until menopause, and then distinctly level off to a plateau. These epidemiologic
      characteristics may indicate that the key etiologic events for these cancers
      occur in the premenopausal period. Prevention strategies that intervene during
      the premenopausal period can be expected to have a greater long-term impact in
      reducing risk than those implemented for an equivalent length of time in the
      postmenopausal years. Epidemiological studies demonstrate a reduction in
      endometrial cancer risk of about 11.7% per year of combination oral contraceptive
      (COC) use; ovarian cancer risk may be reduced by 7.5% per year of COC use, while
      breast cancer studies have produced mixed results. A comparison of age-adjusted
      incidence and mortality rates for women less than 50 years of age between the
      years 1973-1974 and 1986-1987 demonstrate a change in the average rate of breast
      cancer of plus 9.6% incidence and minus 8.2% mortality; the rates reflect the
      cancer burden of women who would and would not have had access to COCs during the
      majority of their child-bearing years. The use of hormone replacement therapy
      (HRT) is well established to provide short-term relief of symptoms related to
      menopause and long-term protection from the consequences of estrogen deficiency,
      such as postmenopausal osteoporosis and cardiovascular disease. Besides COCs, use
      of HRT constitutes the other major setting in which exogenous steroid hormones
      are widely used in essentially healthy women and has had a remarkable impact on
      cancer incidence and mortality. Estrogen replacement therapy (ERT) and
      endometrial cancer risk are strongly associated with respect to both dose and
      duration. Endometrial cell mitotic activity during continuous high-dose estrogen
      monotherapy equals that observed during the follicular phase of the menstrual
      cycle, and the total mitotic activity over a 28-day period amounts to roughly
      double that of a premenopausal woman as long as there is no opposition by a
      progestogen.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7581590
TI  - The importance of life style after menopause.
AB  - There is generally recognized close association between lifestyle and health,
      even if the exact nature, and importance, of various aspects of the relationship
      is under investigation, including that between life style and menopause. However,
      there are abundant and conclusive data showing the positive effect of hormone
      replacement therapy (HRT) on menopausal symptoms and reduction of long-term
      menopausal risks. Much is still to be learned, though, about the reciprocal
      influences of life style, HRT choices, and quality of life. At present the
      opportunity for HRT is somewhat limited, and physicians are to a degree to blame
      in this situation by not vigorously counteracting inaccurate popular perceptions
      of the dangers and benefits of HRT. For purposes of discussion, life style may be
      taken to be a cluster of interrelated behaviour patterns that depend upon social
      and economic conditions, education, age, and other factors. The importance of
      some of these factors in terms of illness and longevity is striking. For
      instance, a study in England revealed a twofold difference in death rate between
      unskilled laborers and self-employed professional--and this difference was also
      applicable to their wives. Income, too, is a determinant of life style. Good
      health is well correlated with higher income. (Some three-quarters of the elderly
      poor are women). Smoking is certainly a life style health factor. In recent
      years, smoking has declined among the upper socioeconomic classes and, indeed,
      these is now a class gradient in lung cancer deaths. Diet is a factor that is
      strongly influenced by geography.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581589
TI  - The risks and benefits of estrogen replacement therapy: Leisure World.
AB  - A women spends about one-third of her life in her postmenopausal years. Some
      women supplement this period of decreased estrogen production with estrogen
      replacement therapy (ERT). Many epidemiologic studies have examined the long-term
      effect of postmenopausal estrogen deprivation and of ERT. Since the 1970s, we
      have evaluated the risks and benefits of ERT in one population of older women in
      the California retirement community of Leisure World. ERT is the most effective
      method for preventing osteoporotic bone loss and fractures in postmenopausal
      women. In Leisure World, ERT reduced the risk of hip fractures by about 50%. The
      effect is greatest in longterm users, but may be lost after discontinuation.
      Postmenopausal osteoporosis affects the bones of the jaws as well as other
      skeletal bones. Bone loss in the jaws may result in tooth loss. In Leisure World,
      estrogen users have retained more natural teeth than nonusers. Cardiovascular
      disease is the leading cause of hospitalization and death in women. In Leisure
      World, ERT reduced the risk of fatal and nonfatal myocardial infarction, ischemic
      heart disease, other heart disease, and stroke by 20-40%. The reduction is
      greatest in long-term and/or current users. ERT is effective in women with and
      without cardiovascular disease risk factors. One of the most feared aspects of
      aging is Alzheimer's disease. In Leisure World, women who had used ERT had a
      reduced risk of Alzheimer's disease. Risk decreased with increasing duration of
      use. Estrogen use, however, is not without risk. Unopposed estrogen increases
      risk of endometrial cancer. Risk increases with increasing years of use and
      remains high after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581591
TI  - Public health. Alcoholism in the elderly.

PMID- 7581592
TI  - Human resources. How much are you worth?

PMID- 7581593
TI  - Sick & tired. Reinventing the public health care system may be its only hope for
      survival.
AB  - As the public health care system continues to slide, the poor are looking
      elsewhere for care. Is there still a way to help them without endangering the
      entire system? Those on the front lines say yes--well, at least maybe--if steps
      are taken now. Fresh ideas, new partnerships--everything is up for grabs in
      today's turbulent times.

PMID- 7581594
TI  - Tell it to someone who cares. The health care industry wants more information-
      and Anne Arundel Health Care Systems is giving it to them.
AB  - The way to succeed in the health care industry these days is to stay ahead of the
      information curve. With a lot of ingenuity and a stern eye on the bottom line,
      Anne Arundel Health Care Systems in Maryland is doing just that. Here's how and
      why they did it, and how much they paid.

PMID- 7581596
TI  - Human resources. Busting barriers.

PMID- 7581595
TI  - As Catholic hospitals begin to merge with for-profit health systems, leaders of
      both are wondering for whom the church bell tolls.
AB  - As Catholic hospitals begin to work with for-profit health systems, leaders on
      both sides are asking themselves whether this is a match made in heaven. (It was
      St. Luke, after all, who first said that you can't serve both God and money).
      With such contrasting missions, can these distinctive entities mesh and still
      stay true to their calling?

PMID- 7581597
TI  - Contracts. Let's make a deal (last longer).

PMID- 7581598
TI  - Outsourcing. Tenet's computer compact.

PMID- 7581599
TI  - Continuing care. Coming 'round the mountain.

PMID- 7581600
TI  - Hospital pulse ... May 1995.

PMID- 7581602
TI  - How Medicare HMOs manipulate the market.

PMID- 7581601
TI  - Energetic thoughts.

PMID- 7581603
TI  - Human resources ... U.S. health care workers can expect a little extra in their
      paychecks next year.

PMID- 7581604
TI  - Payment ... federal government is asking 731 hospitals to repay $9.4 million.

PMID- 7581605
TI  - Consumers ... most Americans want more information to help them pick their health
      care plans, hospitals and doctors.

PMID- 7581606
TI  - Consumers. Getting the word out over the airwaves.

PMID- 7581607
TI  - Leadership ... T. Berry Brazelton was recently given the 1995 C. Everett Koop
      Health Advocate Award.

PMID- 7581608
TI  - Health insurance premiums: rate hikes take a slide.

PMID- 7581609
TI  - Nursing ... two new certifications, one for home health nursing and one for acute
      care nurse practitioner.

PMID- 7581610
TI  - Working smarter, not harder.
AB  - Ask Dr. John Scott to identify the biggest enemy faced by those suffering from
      arthritis, diabetes, and other chronic diseases, and he's likely to tell you that
      doctors don't have the time and support to fight for their patients' best
      interests. Now, after 18 years of practice, Scott has begun blazing new frontiers
      that may revolutionize not only how HMOs and physicians view people with chronic
      diseases, but how the patients view themselves.

PMID- 7581611
TI  - Supplies 'R' us. If time is money, then one-stop shopping is the best deal in
      town.

PMID- 7581612
TI  - Caveat emptor. Scoping out the primary care practice game.

PMID- 7581613
TI  - False metaphors. Sports, competition, and the new leadership paradigm in health
      care.

PMID- 7581614
TI  - Mammograms at the mall.

PMID- 7581615
TI  - Is the Surgeon General obsolete?

PMID- 7581616
TI  - They're back ... are we armed against infectious disease?

PMID- 7581617
TI  - Do you have a green light? Survey gauges doctors' readiness to integrate.

PMID- 7581619
TI  - Telemedicine. A prison plugs in.

PMID- 7581618
TI  - Quality patrol. Technology targets health care.

PMID- 7581620
TI  - Who manages ... who leads?

PMID- 7581621
TI  - Does patient care need a reality check?

PMID- 7581622
TI  - Architectures for intelligent systems based on reusable components.

PMID- 7581623
TI  - One framework, two systems: flexible abductive methods in the problem-space
      paradigm applied to antibody identification and biopsy interpretation.
AB  - Our goal is to build flexible knowledge-based systems which can use a variety of
      problem-solving methods and additional task knowledge, without altering the
      method or task representation. For this purpose, we use a problem-space
      architecture which allows opportunistic adaptation of problem-solving methods
      based on the particular goal, situation and knowledge available. Within this
      framework, we have developed an opportunistic problem-solving method for flexible
      abductive problem solving. The basic method was specified in terms of potential
      subgoals and preferences regarding the order of subgoals. This technique avoids
      specification of any unnecessary procedural commitments, making the resulting
      method very general and robust. We then developed two systems using this basic
      abductive method with additional domain-dependent search-control and task
      knowledge. The additional knowledge alters/overrides some of the minimal
      knowledge provided by the basic method. Behavior of these systems can change
      quite dramatically depending on the added increments of knowledge. Knowledge
      available at runtime shapes the method and hence the behavior. Moreover, even in
      the absence of strong domain knowledge, due to the wide coverage of the basic
      abductive method and the general architecture it is based on, the systems are
      always able to perform some problem solving--they are not brittle. The specific
      systems implemented are RedSoar and LiverSoar in the domain of red blood cell
      antibody identification and liver biopsy interpretation, respectively. We discuss
      the designs, implementations and evaluations of these systems, emphasizing the
      role the flexible abductive problem-solving method plays.

PMID- 7581624
TI  - A case study in ontology library construction.
AB  - The goal of our work is to facilitate the development of medical knowledge-based
      systems by providing a library of reusable ontologies. The availability of such a
      library reduces the amount of knowledge acquisition required to create knowledge
      bases of new applications, and makes it easier to connect a knowledge-based
      system to existing data bases. This article presents a case study in constructing
      such a library. The emphasis is on studying the principles that underly the
      internal structure of the library as well as on the process of constructing and
      using the library. We envision that, in the future, application ontologies can be
      constructed by the selection and refinement of generic ontologies and domain
      ontologies from such a library.

PMID- 7581625
TI  - Ontology-based configuration of problem-solving methods and generation of
      knowledge-acquisition tools: application of PROTEGE-II to protocol-based decision
      support.
AB  - PROTEGE-II is a suite of tools and a methodology for building knowledge-based
      systems and domain-specific knowledge-acquisition tools. In this paper, we show
      how PROTEGE-II can be applied to the task of providing protocol-based decision
      support in the domain of treating HIV-infected patients. To apply PROTEGE-II, (1)
      we construct a decomposable problem-solving method called episodic skeletal-plan
      refinement, (2) we build an application ontology that consists of the terms and
      relations in the domain, and of method-specific distinctions not already captured
      in the domain terms, and (3) we specify mapping relations that link terms from
      the application ontology to the domain-independent terms used in the problem
      solving method. From the application ontology, we automatically generate a domain
      specific knowledge-acquisition tool that is custom-tailored for the application.
      The knowledge-acquisition tool is used for the creation and maintenance of domain
      knowledge used by the problem-solving method. The general goal of the PROTEGE-II
      approach is to produce systems and components that are reusable and easily
      maintained. This is the rationale for constructing ontologies and problem-solving
      methods that can be composed from a set of smaller-grained methods and
      mechanisms. This is also why we tightly couple the knowledge-acquisition tools to
      the application ontology that specifies the domain terms used in the problem
      solving systems. Although our evaluation is still preliminary, for the
      application task of providing protocol-based decision support, we show that these
      goals of reusability and easy maintenance can be achieved. We discuss design
      decisions and the tradeoffs that have to be made in the development of the
      system.

PMID- 7581626
TI  - The NST-EXPERT project: the need to evolve.
AB  - NST-EXPERT is a medical expert system designed to evaluate fetal condition
      (especially in 'high risk' pregnancies). The system reasons based on data from
      the Non-Stress Test (NST), a monitoring test widely used in obstetrics. From
      specific limited maternal-fetal context information together with the analysis of
      the NST results the system infers a diagnosis for each case, elaborates a
      therapeutic plan, and suggests a prognosis of an early neonatal outcome. This
      article describes a new version based on a previous research prototype. Such
      systems can aid clinicians of varied experience in assessing and managing
      complicated pregnancies.

PMID- 7581627
TI  - Model-based diagnosis of brain disorders: a prototype framework.
AB  - This paper describes a prototype framework, named NEUROLAB, dedicated to research
      and diagnosis in the area of brain disorders. The diagnostic task uses a blending
      of factual knowledge, formal knowledge, and experiential knowledge. The
      prototype's first target clinical application is partial seizures in epilepsy.
      Diagnosis is carried out using qualitative electroencephalographic descriptions,
      clinical attack pattern descriptions, and pre- and post-ictal observations. From
      this information, the system builds explanations in the form of candidate
      epileptogenic foci and trajectories of the seizure spread. Hypothesis-testing and
      discrimination is based on minimal set coverage, and consistency-checking is
      performed using the general background knowledge. Upon completion, NEUROLAB will
      provide specific physiological knowledge for solving the so-called inverse
      problems in electroencephalography (EEG) and magnetoencephalography (MEG).

PMID- 7581628
TI  - VIA-RAD: a blackboard-based system for diagnostic radiology. Visual Interaction
      Assistant for Radiology.
AB  - The work described in this article presents an approach to the integration of
      computer-displayed radiological images with cooperative computerized assistance
      for decision-making. The VIA-RAD system (Visual Interaction Assistant for
      Radiology) is a blackboard-based architecture, founded on extensive data
      collection and analysis in the domain of diagnostic radiology, together with
      cognitive modeling of the interaction between perception and problem-solving. The
      details of this system are presented in terms of domain knowledge representation
      and domain knowledge mapping. A small prototype of the system has been
      implemented and tested with radiology subjects, and the results of this study are
      also described.

PMID- 7581630
TI  - Malaria transmitted by mosquitoes in New York City.

PMID- 7581629
TI  - An algorithm for complete enumeration of the mechanisms of supraventricular
      tachycardias that use multiple atrioventricular, AV nodal, and/or Mahaim
      pathways.
AB  - The EINTHOVEN system is a model-based expert system that interprets the cardiac
      rhythm from the electrocardiogram. It simulates the expected behavior of
      realistic semi-quantitative cardiac models constructed by heuristic rules to
      generate interpretations that include both text descriptions and event-by-event
      causal explanations in the form of ladder diagrams. The simulation has been
      limited by an inability to predict all possible behaviors of hearts with more
      than one reentrant circuit. We now describe an algorithm that overcomes this
      limitation. Its output has been validated by an independent possibility-tree
      analysis. Timing and storage measurements are presented for models with up to
      three slow atrioventricular nodal pathways, four atrioventricular pathways, and a
      single atriofascicular (Mahaim) pathway. This is the first report in the
      literature of an algorithm that enumerates all possible mechanisms for reentrant
      supraventricular tachycardias that use atrioventricular, atrioventricular nodal,
      and/or atriofascicular pathways in humans.

PMID- 7581631
TI  - Scalp ringworm in London.

PMID- 7581632
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7581633
TI  - British soldier returns from Bosnia with HFRS.

PMID- 7581634
TI  - Legionnaires' disease associated with Turkey: update.

PMID- 7581635
TI  - School-based health clinics in the mid-1990s.
AB  - School-based health clinics have grown in number from one or two in the early
      1970s to more than 600 in the 1990s. The main focus of school-based clinics is to
      provide primary health care and psychosocial counseling to children and
      adolescents in schools. This article reviews the distribution and availability of
      school-based clinics in 1994, discussing various models and definitions for
      school-based health services, the health and educational impact of school-based
      clinics on adolescents, and the policy issues of concern to school-based health
      clinics in the current era of health care and health financing reform.

PMID- 7581636
TI  - Condom availability and prevention issues for adolescents.
AB  - Sexual activity among adolescents in the United States increased during the 1970s
      and 1980s but appears to be leveling off in the early 1990s. Condom use among
      sexually active adolescents has been irregular and variable. Recent trends,
      however, suggest that teenagers may be using condoms more often. More than half
      of all high school students used a condom at last intercourse in a nationwide
      survey. The most recent data about adolescent sexual activity and condom use are
      summarized, and recent studies examining attitudes and beliefs about condoms are
      reviewed. Many authors suggest that knowledge alone may be insufficient to change
      adolescent behavior in regard to condoms. The importance of understanding
      cultural norms and the social meaning of condoms among groups of teenagers is
      discussed. Differentiating disease protection from pregnancy prevention is also
      examined. Suggestions are made regarding strengthening condom negotiating skills
      in individuals. Recently published accounts of communities that have adopted
      condom programs in their schools by successfully addressing political obstacles
      are outlined.

PMID- 7581637
TI  - Hepatitis B immunization among adolescents.
AB  - Prior to this year, little has been written regarding the immunization of the
      adolescent population against hepatitis B. Most studies have focused on the
      immunization of infants, children, and adults, highlighting concerns about
      adolescent compliance with such an immunization program. The body of literature
      about hepatitis B immunization among adolescents has grown, and there is much to
      learn in preparation for the implementation of the immunization Practices
      Advisory Committee's most recent recommendation to immunize all 11- and 12-year
      old children in the United States who have not previously been immunized against
      hepatitis B.

PMID- 7581638
TI  - New contraceptives in the 1990s.
AB  - This article reviews the contraceptive methods levonorgestrel implants and depot
      medroxyprogesterone acetate. These methods provide effective and safe
      contraception for adolescents and adults. This review focuses on the use of these
      contraceptive techniques in the adolescent population, discussing patient
      selection, side effects, and controversies concerning the methods. Future
      hormonal contraceptive methods are also discussed.

PMID- 7581639
TI  - Reproductive health in young people with cystic fibrosis.
AB  - The improving survival rates of young people with cystic fibrosis now results in
      reproductive health being of greater significance than previously. This article
      reviews how cystic fibrosis affects the reproductive health of male and female
      patients with this chronic illness, highlights recent advances, and identifies
      some deficiencies that still exist in our understanding of reproductive health in
      cystic fibrosis. A further aim is to encourage health professionals to discuss
      reproductive health issues with their adolescent and adult patients.

PMID- 7581640
TI  - Attention-deficit hyperactivity disorder in children.
AB  - Attention-deficit hyperactivity disorder has been redefined in the
      classifications in the International Classification of Disease, 10th revision and
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition. The
      definitions are more concordant than their predecessors and reemphasize the
      distinction between inattentiveness and hyperactivity. The causes and mechanisms
      are still uncertain, but dietary sugar or aspartame and thyroid dysfunction do
      not seem to be major factors. Specific subgroups, such as children with comorbid
      psychologic disorders, tic disorders, or mental handicap, seem to have different
      origins, natural history, prognoses, and responses to treatment, reflecting the
      heterogeneous nature of the disorder. Psychostimulant therapy has unquestioned
      short-term effects on behavior but less certain benefits on long-term
      psychosocial outcome or on academic performance.

PMID- 7581641
TI  - Anxiety disorders in children and adolescents.
AB  - Anxiety disorders are common in children and adolescents and may be associated
      with significant suffering, disruptions of normal psychosocial and academic
      development, disruption of family functioning, and increased utilization of
      medical services. They are frequently chronic disorders. Effective early
      interventions for children and adolescents with anxiety disorders may reduce or
      eliminate potentially life-long suffering and impairment.

PMID- 7581642
TI  - Diagnosis, treatment, and neurobiology of autism in children.
AB  - Autism is a developmental neuropsychiatric disorder defined by the presence of
      social and communicative deficits, restricted and repetitive behaviors and
      interests, and a characteristic course. Research suggests that hereditary factors
      play a principal role in the etiology of most cases. A phenotype broader than
      autism, including milder social and language-based cognitive deficits, appears to
      be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms
      clearly underlie the disorder. Neuropathologic studies have demonstrated
      abnormalities in limbic structures, the cerebellum, and the cortex. New advances
      in behavioral therapies and pharmacologic treatment are important components of
      successful multidisciplinary treatment of this disorder.

PMID- 7581643
TI  - Advances in the study of mood disorders in childhood and adolescence.
AB  - Studies summarized in this review explore the nosology, course, and treatment of
      depression. The observation that depressive disorders in children often occur in
      conjunction with other psychiatric symptoms seems to affect outcome--in terms of
      suicidal behavior and possibly recurrence. Family factors seem to contribute to
      the severity of depressive symptoms, and it is possible that the level of
      criticism, as operationalized by "expressed emotion," is one of the mediating
      factors. Unfortunately, although several studies addressed treatment, both
      psychopharmacologically and psychotherapeutically, it is clear that considerably
      more research is needed before effective interventions are found for serious and
      disabling mood disorders in youth.

PMID- 7581644
TI  - Child sexual abuse.
AB  - The enormous media interest in the frequency and effects of child sexual abuse
      (CSA) has been paralleled in the past year by significant advances in our
      empirical knowledge about this childhood risk factor for adult psychosocial
      problems. Progress has been made in the diagnostic procedures employed in CSA
      physical examinations, in our understanding of the link between CSA and
      subsequent psychiatric morbidity, and in our cognizance of the effects that
      trauma, such as CSA, may have on memory.

PMID- 7581645
TI  - Childhood exanthems.
AB  - Childhood exanthems are a common cause of skin disease in children. Several new
      aspects of exanthems are reviewed. Two conditions, unilateral laterothoracic
      exanthem and asymmetric periflexural exanthem, may be variations of the same
      disease and could potentially represent a cutaneous reaction to several
      infectious agents. An eruption that has been called papular-purpuric gloves and
      socks syndrome is usually, but not invariably, caused by parvovirus B19
      infection. Another unusual exanthem, eruptive pseudoangiomatosis, is also
      discussed. Finally, several new developments in the etiology and disease spectrum
      of exanthem subitum are emphasized.

PMID- 7581646
TI  - Minimizing the pain of office procedures in children.
AB  - Office practitioners are often required to perform painful procedures on
      children. A wide variety of techniques that minimize the physical and psychologic
      trauma of the procedure are reviewed. Various methods of accomplishing some
      common procedures are evaluated.

PMID- 7581647
TI  - Environmental skin injuries in children.
AB  - Recently, interest in the potential impact of the environment on our general
      health has heightened. Particular focus has been directed toward environmental
      skin injuries because the integument, the only organ of the body that is
      constantly exposed to the surrounding environment, directly demonstrates the
      damaging effects of the environment and thereby allows for direct visual
      recognition by both physicians and laypersons. The characteristic cutaneous
      features, physiologic responses, therapeutic approaches to promote healing, and
      preventive measures that may be taken to avoid future environmental injury are
      discussed. The scope of environmental injuries to the skin is extremely vast;
      therefore, the focus of this review is limited to cutaneous injuries that may
      result as a consequence of ultraviolet irradiation, marine life, and electrical
      forces.

PMID- 7581648
TI  - Endocrine and metabolism.

PMID- 7581649
TI  - Ligand-independent hormone secretion.
AB  - The secretion of many hormones is regulated by extracellular signals, such as
      hormones, growth factors, neurotransmitters, and ions, that mediate signal
      transduction via a G protein-coupled pathway. Three components comprise the G
      protein-coupled pathway: the G protein-coupled receptor, the G protein, and the
      effector. G protein-coupled receptors allow cells to respond to external stimuli
      and comprise a large superfamily with hundreds of members. G proteins function as
      signal transducers between ligand-bound receptors and intracellular effectors. G
      protein-regulated effectors include enzymes of second messenger metabolism, such
      as adenylyl cyclase, phospholipase C, cyclic GMP phosphodiesterase, and ion
      channels. Abnormalities in any of these three components alter signal
      transduction and can lead to human disease. For example, mutations of G protein
      coupled receptors that promote G protein activation in the absence of an agonist
      cause retinitis pigmentosa, hyperthyroidism due to hyperfunctioning thyroid
      adenomas and thyroid hyperplasia, male-limited precocious puberty, and
      hypocalcemia. Human disorders attributed to constitutively activating mutations
      of the alpha subunit of Gs include the McCune-Albright syndrome,
      adrenocorticotropic hormone-independent Cushing's syndrome, and functional
      endocrine tumors.

PMID- 7581650
TI  - Interactions of the endocrine and immune systems in children and young adults.
AB  - In the recent past, we have seen novel information on the bidirectional
      interactions between the endocrine and immune systems. Thus, the central nervous
      system, through the hypothalamic-pituitary-adrenal axis and the peripheral
      autonomic and sensory systems, influences the quantity and the quality of the
      immune and inflammatory reactions. The latter, on the other hand, regulates the
      activity of the endocrine system by influencing its central and peripheral
      components. The reciprocal effects of the two systems on each other are adaptive
      and help survival of the self and species. Dysregulation or chronic alterations
      of the endocrine system can, however, increase the susceptibility of individuals
      to various diseases or lead to frank pathologic states.

PMID- 7581652
TI  - Recent advances in the immunopathogenesis of insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus places a major burden on both affected
      individuals and society because of its high morbidity and mortality rates and
      financial costs. That the disease occurs in genetically susceptible individuals
      as a result of an immunologically mediated process thought to be triggered by
      environmental factors probably operating in early childhood is well established.
      Enhanced knowledge of the immunopathogenesis, genetics, and natural history of
      insulin-dependent diabetes mellitus in nonobese diabetic mice and humans has
      enabled investigators to better predict disease onset and design therapies aimed
      at its prevention. Major national and international multicenter trials are
      currently in progress, engendering cautious optimism that the disease may safely
      be prevented.

PMID- 7581651
TI  - Parental genomic imprinting.
AB  - Parental, or genomic, imprinting is a newly described form of genetic regulation,
      leading to the differential behavior of each parental copy of a gene. The precise
      mechanism responsible for the imprint, or allele-specific behavior of gene
      transcription, is still unclear; it is thought that modifications not involving
      the DNA base sequence (therefore, epigenetic as opposed to genetic) have occurred
      during the production of egg and sperm that mark genes according to parental
      origin. Several imprinted genes have been identified that also show allelic
      differences in cytosine methylation and in the timing of their replication during
      cell division; the relevance of this finding to imprinting mechanisms awaits
      further clarification. Despite our incomplete knowledge, the importance of the
      field of imprinting to the pediatrician is in its contribution to our
      understanding of the transmission behavior of many human diseases and syndromes,
      particularly those involving abnormal growth and development. Recent advances in
      the field will no doubt lead to more widely available diagnostic tools with
      potential applications as far-reaching as the investigation of unexplained fetal
      loss, prenatal diagnosis, and disease risk counseling.

PMID- 7581654
TI  - An 11-year-old boy with vomiting, dehydration, and a tan complexion.

PMID- 7581653
TI  - Complications of growth hormone therapy in children.
AB  - The introduction of human growth hormone (GH) prepared by recombinant DNA
      technology has resulted in increased numbers of children and adults receiving
      treatment. This trend has led to questions concerning the safety of GH,
      particularly when used for indications other than GH deficiency. This review
      discusses the effects of GH on fluid, lipid, and carbohydrate metabolism; the
      risk of intracranial hypertension or pseudotumor cerebri; the effects on the
      skeletal system; the risk of malignancy; and the effects on the immune system. At
      present, GH treatment appears to be safe, although long-term follow-up of GH
      treated patients is necessary.

PMID- 7581655
TI  - Immunizations, animal-induced injuries and disease, neonatal jaundice, and viral
      infections.
AB  - Four areas of concern for the pediatric practitioner are examined by the review
      of recent literature on the topics of immunization, animal-induced illness and
      injury, neonatal jaundice, and viral infections. An attempts to place these
      subjects into the perspective of the primary care office and into the current
      social and political climate as it applies to health care will also be made. By
      highlighting the literature of the past year on the above categories, I hope to
      provide topical information for pediatricians as they care for patients and their
      families.

PMID- 7581656
TI  - Growth and storage of Agrobacterium.

PMID- 7581657
TI  - Transformation of soybean (Glycine max) via Agrobacterium tumefaciens and
      analysis of transformed plants.

PMID- 7581658
TI  - Agrobacterium-mediated transformation of potato genotypes.

PMID- 7581659
TI  - Agrobacterium-mediated transformation of soft fruit Rubus, Ribes, and Fragaria.

PMID- 7581660
TI  - High-frequency and efficient Agrobacterium-mediated transformation of Arabidopsis
      thaliana ecotypes "C24" and "Landsberg erecta" using Agrobacterium tumefaciens.

PMID- 7581661
TI  - Transformation protocols for broadleaved trees.

PMID- 7581662
TI  - Agrobacterium virulence.

PMID- 7581663
TI  - Agrobacterium-mediated antibiotic resistance for selection of somatic hybrids.
      The genus Lycopersicon as a model system.

PMID- 7581664
TI  - Histochemical GUS analysis.

PMID- 7581665
TI  - Fluorometric GUS analysis for transformed plant material.

PMID- 7581667
TI  - The plant oncogenes rolA, B, and C from Agrobacterium rhizogenes. Effects on
      morphology, development, and hormone metabolism.

PMID- 7581666
TI  - The detection of neomycin phosphotransferase activity in plant extracts.

PMID- 7581668
TI  - Quantifying polyamines in Agrobacterium rhizogenes strains and in Ri plasmid
      transformed cells.

PMID- 7581670
TI  - Quantifying phytohormones in transformed plants.

PMID- 7581669
TI  - IAA analysis in transgenic plants.

PMID- 7581671
TI  - Manipulating photosynthesis in transgenic plants.

PMID- 7581672
TI  - Gene activation by T-DNA tagging.

PMID- 7581673
TI  - Agrobacterium tumefaciens chemotaxis protocols.

PMID- 7581674
TI  - Assessing cadmium partitioning in transgenic plants.

PMID- 7581675
TI  - Overexpression of chloroplastic Cu/Zn superoxide dismutase in plants.

PMID- 7581676
TI  - Agroinfection.

PMID- 7581677
TI  - T-DNA transfer to maize plants.

PMID- 7581680
TI  - Effect of acetosyringone on growth and oncogenic potential of Agrobacterium
      tumefaciens.

PMID- 7581678
TI  - Use of cosmid libraries in plant transformations.

PMID- 7581679
TI  - Regulation of Agrobacterium gene manipulation.

PMID- 7581681
TI  - Transgenic oilseed rape. How to assess the risk of outcrossing to wild relatives.

PMID- 7581682
TI  - Electroporation protocols for Agrobacterium.

PMID- 7581683
TI  - Binary Ti plasmid vectors.

PMID- 7581684
TI  - Leaf disk transformation.

PMID- 7581685
TI  - Agrobacterium-mediated transformation of protoplasts from oilseed rape (Brassica
      napus L.).

PMID- 7581686
TI  - Agrobacterium-mediated transformation of stem disks from oilseed rape (Brassica
      napus L.).

PMID- 7581688
TI  - Simple cultural tests for identification of Agrobacterium biovars.

PMID- 7581689
TI  - SEQHUNT. A program to screen aligned nucleotide and amino acid sequences.

PMID- 7581687
TI  - Peanut transformation.

PMID- 7581691
TI  - Murine monoclonal antibody development.

PMID- 7581690
TI  - Purification of reduced and alkylated antibody subunits.

PMID- 7581692
TI  - Comparative properties of polyclonal and monoclonal antibodies.

PMID- 7581693
TI  - Evaluation of antibody clonality.

PMID- 7581695
TI  - Molecular modeling of antibody-combining sites.

PMID- 7581694
TI  - Affinity immunoblotting.

PMID- 7581696
TI  - Epitope and idiotope mapping using monoclonal antibodies.

PMID- 7581698
TI  - Catalytic antibodies. Structure and possible applications.

PMID- 7581697
TI  - Anti-idiotypic antibodies that mimic opioids.

PMID- 7581699
TI  - Preparation and assay of acetylcholinesterase antibody.

PMID- 7581700
TI  - DNA hydrolysis by antibodies.

PMID- 7581701
TI  - Screening strategies for catalytic antitransition-state analog antibodies.

PMID- 7581702
TI  - Expression of chimeric immunoglobulin genes in mammalian cells.

PMID- 7581703
TI  - Single-chain anti-DNA FV.

PMID- 7581704
TI  - Molecular cloning of antiground-state proteolytic antibody fragments.

PMID- 7581705
TI  - Cloning and bacterial expression of an esterolytic sFV.

PMID- 7581707
TI  - Synthetic antibody gene libraries for in vitro affinity maturation.

PMID- 7581706
TI  - Site-directed mutagenesis of antibody-variable regions.

PMID- 7581708
TI  - Chaperonins in phage display of antibody fragments.

PMID- 7581709
TI  - Phage-display libraries of murine and human antibody Fab fragments.

PMID- 7581710
TI  - Selection of human immunoglobulin light chains from a phage-display library.

PMID- 7581711
TI  - Purification of antibody light chains by metal affinity and protein L
      chromatography.

PMID- 7581712
TI  - Rapid purification of recombinant antibody fragments for catalysis screening.

PMID- 7581713
TI  - Assay of radiolabeled VIP binding and hydrolysis by antibodies.

PMID- 7581714
TI  - Methods of measuring thyroglobulin and peptide-methylcoumarinamide hydrolysis by
      autoantibodies.

PMID- 7581715
TI  - Radiolabeling of antibodies for therapy and diagnosis.

PMID- 7581716
TI  - Structure and properties of human immunoglobulin light-chain dimers.

PMID- 7581718
TI  - Detection of human variable gene family expression at the single-cell level.

PMID- 7581717
TI  - Crystallographic and chromatographic methods for study of antibody light chains
      and other proteins.

PMID- 7581719
TI  - Influence of budesonide on the response to inhaled terbutaline in children with
      mild asthma.
AB  - The aim of this study was to evaluate if continuous treatment with budesonide or
      salmeterol influences the bronchodilator response to terbutaline in children with
      asthma; 23 children, aged 7 to 16 years (mean = 11 years), with mild asthma were
      treated with inhaled budesonide 100 micrograms b.i.d. and placebo for three weeks
      in a randomized, double blind crossover study. These treatments were followed by
      treatment with inhaled salmeterol 50 micrograms b.i.d. for 3 weeks. On the last
      day of each period a cumulative dose-response experiment with terbutaline in the
      doses 50, 100, 250 and 500 micrograms (cumulative dose 900 micrograms) was
      performed. Lung function was measured before and 20 min after each terbutaline
      inhalation. Baseline pulmonary functions after budesonide treatment were
      significantly higher than the baseline measured after the two other treatments (p
      < 0.05). After budesonide treatment, the dose-response curve was shifted
      vertically upwards but otherwise parallel to the dose-response curve after
      placebo. The increase from baseline after the first cumulative dose of
      terbutaline was significantly lower after salmeterol treatment than after the two
      other treatments (p < 0.01). Maximal lung functions after 900 micrograms
      terbutaline also differed significantly between the three dose-response days;
      budesonide being significantly higher and salmeterol significantly lower than
      placebo (p = 0.02 and p < 0.001, respectively). It is concluded that budesonide
      treatment does not enhance the brochodilator response to terbutaline. Further
      studies are needed to assess if long-term continuous salmeterol treatment reduces
      the response to terbutaline.

PMID- 7581720
TI  - Individual time-courses of ECP and EPX during allergen provocation tests in
      asthmatic children.
AB  - To study the time-course of eosinophil cationic protein (ECP) and eosinophil
      protein X (EPX) during bronchial allergen provocation, we investigated 32
      asthmatic children sensitive to house-dust mites as well as 6 non-atopic young
      adult controls. In all subjects, allergen challenges were performed with house
      dust mite extracts of Dermatophagoides pteronys-sinus or Dermatophagoides
      farinae. Blood samples were taken at regular intervals during the 24-h
      observation period. The individual time-courses of ECP and EPX revealed different
      characteristic groups of patterns: (1) an isolated early serum peak of both
      mediators during or within the first 60 min after provocation (2) an early plus a
      late peak (3) an isolated late peak 12 h after provocation (4) an isolated late
      peak 24 h after provocation, and (5) no significant variation during the 24-h
      observation period. The early peak could be due to short-term changes in
      eosinophil activation, while late peaks may reflect eosinophil proliferation,
      recruitment, subsequent priming and enhancing of the propensity to release their
      proteins. ECP and EPX showed a corresponding parallel time-course in nearly all
      challenges, with EPX-concentration exceeding that of ECP. There was no
      correlation between ECP/EPX serum concentrations and clinical parameters such as
      lung function data. From our results we conclude that the striking groups of time
      courses of ECP/EPX serum concentration indicate different uniform patterns of
      eosinophil activation during allergen challenge-but do not predict clinical
      outcome of provocation. The role of the eosinophil in early asthmatic reactions
      remains to be established in further studies.

PMID- 7581721
TI  - Mucosal T cells recovered from mice after infection with respiratory syncytial
      virus display a memory/activation phenotype.
AB  - Pgp-1 expression was studied as a marker of memory/activation on systemic and
      mucosal T cells of BALB/c and C57BL/6 mice after infection with respiratory
      syncytial virus (RSV), using two-color dual fluorescence flow cytometry employing
      anti-L3T4 (CD4), anti-Ly2 (CD8), and anti-Pgp-1 (CD44) monoclonal antibodies. Pgp
      1 was expressed in relatively low densities on T cells of C57BL/6 mice, allowing
      differentiation of a dual population of Pgp-1(10) and Pgp-1hi T cells after
      antigenic stimulation in vivo. On the contrary, T cells of BALB/c mice were
      uniformly Pgp-1hi, making this mouse strain less suitable for studies with this
      marker. In blood and spleen consistently more CD8+ than CD4+ T cells were Pgp
      1hi, while in BAL more CD4+ than CD8+ T cells were Pgp-1hi. After primary but not
      after secondary infection, CD4+ Pgp-1hi T cells increased significantly in the
      blood and spleen. After secondary infection both CD4+ Pgp-1hi and CD8+ Pgp-1hi T
      cells increased in the BAL. It is hypothesized that after primary infection
      systemic RSV-specific T cells acquire an activation/memory phenotype as
      characterized by an enhanced expression of Pgp-1, resulting in a faster and
      stronger influx of these cells in the lungs after secondary infection.

PMID- 7581723
TI  - Evaluation of the child with suspected primary immunodeficiency.
AB  - Infections are one of the major causes for visits to paediatricians. Most
      children recover without sequelae, untreated or if treated properly, and develop
      specific immunity towards the challenging microorganisms (mostly viruses). There
      is a small proportion of children however, with unusual frequent, severe,
      chronic, recurrent or opportunistic infections in whom an underlying
      immunodeficiency must be suspected. Based on current knowledge about the major
      types of congenital immunodeficiencies this review suggests a diagnostic approach
      to these children. Early evaluation will allow early identification of affected
      children and, subsequently, lead to proper treatment before devastating
      infections cause irreversible organ damage.

PMID- 7581724
TI  - Functional assessment of CD2, CD3 and CD28 on the surface of peripheral blood T
      cells from infants at low versus high genetic risk for atopy.
AB  - Recent studies from several laboratories suggest that the rate of postnatal
      maturation of T-cell function(s) associated with in vitro activation may be
      slower in children at high genetic risk for atopy (HR), compared to their normal
      (low risk; LR) counterparts. The present study compared the in vitro activity of
      the function-associated surface molecules CD2, CD3 and CD28 in panels of 27 HR
      and 13 LR infants, with a reference panel of 10 adults, employing assay systems
      involving T-cell stimulation with MoAbs against these molecules. The response
      maxima induced by saturating levels of the MoAbs were equivalent in all 3 groups,
      but T-cells from the HR infants required 10-50 fold higher levels of anti-CD3
      stimulation to attain their maximum response, relative to adults (p = 0.02); T
      cells from LR infants were also less responsive to anti-CD3 than adults, but
      these differences were smaller and did not attain statistical significance. It is
      suggested that these differences are attributable to varying proportions of
      competent T-memory cells (which respond to low levels of anti-CD3) in PBL from
      these populations, the postnatal accumulation of which proceeds slowest in the HR
      group.

PMID- 7581725
TI  - T-cell "priming" against environmental allergens in human neonates: sequential
      deletion of food antigen reactivity during infancy with concomitant expansion of
      responses to ubiquitous inhalant allergens.
AB  - The study below comprises prospective analysis of patterns of allergen-specific T
      cell reactivity in a cohort of 23 children bled at regular intervals from 6-10
      weeks to 2 years of age, together with cross sectional studies on panels of cord
      and adult blood samples. The results indicate reciprocal patterns of responses to
      dietary and inhalant allergens, the former being frequent in infancy but rare in
      adults, whereas the latter are preserved and expand between infancy and
      adulthood. These findings are consistent with a recently proposed model for the
      development of immunity to environmental allergens which involves allergen-driven
      T-cell "selection" during early life leading to deletion of food allergen
      specific T-cells via the induction of specific anergy, with concomitant selection
      and ultimately expansion of mutually exclusive TH-1-like or TH-2-like reactivity
      to inhalant allergens via Immune Deviation mechanisms.

PMID- 7581722
TI  - Postnatal maturation of immune competence during infancy and childhood.

PMID- 7581726
TI  - Effect of intravenous gammaglobulin (IVIG) on the platelet count in patients with
      Wiskott-Aldrich syndrome.
AB  - The ability of IVIG to increase platelet counts in patients with idiopathic
      thrombocytopenic purpura suggests its potential usefulness in other disease
      states characterized by low platelet counts. This possibility was evaluated in
      nine patients with the Wiskott-Aldrich syndrome (WAS) who received IVIG, at a
      dose of 400 mg/kg every 4 weeks. The mean platelet count prior to institution of
      IVIG was 32,000/cumm (range 2,400 to 98,000). Following administration of IVIG,
      the platelet count ranged between 5,000 and 85,000/cumm. There were no immediate
      increases in platelet counts after IVIG infusion in any patient who had serial
      platelet counts. During treatment, patients were not given any routine platelet
      transfusions for low platelet counts. However, while on IVIG, two patients showed
      a good response to platelet transfusion prior to surgical procedures. In
      conclusion, chronic IVIG therapy does not appear to affect platelet counts in
      patients with the Wiskott-Aldrich syndrome.

PMID- 7581727
TI  - Selective expansion of T cells expressing V beta 2 in peanut allergy.
AB  - Peanuts are the most common cause of fatal and near-fatal food-induced
      anaphylaxis. The immune basis for susceptibility to peanut allergy is poorly
      understood. The current study examined the possibility that patients with peanut
      allergy, as compared to normals, use different T cell receptor variable beta
      regions (V beta) in the recognition of peanuts. The results demonstrate that
      stimulation of T cells from patients with peanut allergy results in the selective
      expansion of V beta 2+ T cells.

PMID- 7581729
TI  - XIII Annual Scientific Meeting of the British Blood Transfusion Society and
      Scotblood 1995. Stirling, United Kingdom, 1-4 September 1995. Abstracts.

PMID- 7581728
TI  - Elevated levels of serum antibodies to the lectin wheat germ agglutinin in celiac
      children lend support to the gluten-lectin theory of celiac disease.
AB  - Lectins recognize carbohydrate moities of glycoproteins and glycolipids, and can
      elicit several biological effects, including cell agglutination, cell activation
      and mitogenesis. According to the gluten-lectin theory, celiac lesions represent
      a response to a toxic lectin, putatively wheat germ agglutinin (WGA). In this
      study we compared the serum antibody levels IgA, IgG and IgM to WGA and to
      gliadin in children under investigation for celiac disease (CD), as compared to
      reference children. We found that the levels of IgA and IgG to WGA as well as
      gliadin were significantly higher in celiac children on a gluten-containing diet,
      compared to children on gluten-free diet and reference children. These findings
      lend support to the concept that WGA is a biologically significant component of
      gluten. Since WGA can mimic the effects of epidermal growth factor (EGF) at the
      cellular level, we hypothesize that the crypt hyperplasia seen in celiac children
      could be due to a mitogenic response induced by WGA.

PMID- 7581730
TI  - Putting knowledge about change into practice. Proceedings of a conference. Kansas
      City, Missouri, September 26-27, 1994.

PMID- 7581731
TI  - Emerging themes in efforts to improve the quality of health care: overview.

PMID- 7581732
TI  - The origins and evolution of peer review organizations.

PMID- 7581733
TI  - Lessons for guidelines from the diffusion of innovations.

PMID- 7581735
TI  - The NIH consensus development program.
AB  - The NIH CDCs are a highly visible, public forum to evaluate controversial medical
      technologies by synthesizing current medical science data. The consensus
      statements, although not intended as medical practice guidelines, may form part
      of the database preceding guideline formulation. It is difficult to assess the
      effect of the conferences on physician practice, in part reflecting the
      interference of the many other influences, medical and nonmedical, on physician
      behavior. Yet the program has had some success in influencing reimbursement
      policy for some technologies here and abroad and in influencing specialty
      organization policy, thereby indirectly affecting physician behavior. On the
      other hand, OMAR's dissemination activities have apparently been so successful
      that demand for CDC statements has more than doubled over the past five years,
      prompting OMAR to establish an information service (including fax and the
      Internet). And finally, the program has spawned consensus conferences throughout
      the world, including Canada, Western Europe, and Israel (Goodman & Baratz 1990).

PMID- 7581736
TI  - The community clinical oncology program: its effect on clinical practice.

PMID- 7581734
TI  - The shape of resistance ... the shapers of change.

PMID- 7581737
TI  - Changing the health promotion behaviors of primary care physicians: lessons from
      two projects.

PMID- 7581738
TI  - Changing health care practices in Medicare's Health Care Quality Improvement
      Program.

PMID- 7581740
TI  - Integrating behavioral and systems strategies to change clinical practice.

PMID- 7581739
TI  - Organizational strategies for implementing clinical guidelines.

PMID- 7581741
TI  - Measurement and accountability: taking careful aim.

PMID- 7581742
TI  - Promises and hazards of strategies to implement change.

PMID- 7581743
TI  - Notes from the field: changing peer review.

PMID- 7581744
TI  - Measurement of ATPases in red cells: setting up and validation of a highly
      reproducible method.
AB  - Our aim was to set up and validate a reproducible method to study ATPase family
      on erythrocyte membranes. We compared several methods for erythrocyte washing and
      hemolysis and succeeded in preparing completely hemoglobin-free membrane ghosts
      still bearing intact ATPases. We compared the conventional incubation procedure
      with the coupled enzyme assay to measure Na-K-Mg, Ca-Mg and Mg ATPase on the
      membranes. A significant difference was constantly observed between the results
      by these methods, the values by the incubation procedure being 28, 57 and 58% of
      the respective values obtained by the linked enzyme assay. By adopting this last
      one, we obtained uniform and reproducible results in 31 healthy subjects. The
      following activities of the measured pumps resulted: Na-K-Mg ATPase 0.026 +/-
      0.007, mean +/- SD; Ca-Mg ATPase 0.030 +/- 0.010, and Mg ATPase 0.017 +/- 0.003
      U/mg protein, respectively. Finally, we investigated the effect of membrane
      storage time and temperature on ATPase results.

PMID- 7581745
TI  - Translational control of eukaryotic gene expression. Role of the guanine
      nucleotide exchange factor and chain initiation factor-2.
AB  - In mammalian cells, the guanine nucleotide exchange factor (GEF or eIF-2B) is a
      key regulator of polypeptide chain initiation. The exchange of GDP bound to chain
      initiation factor 2 (eIF-2) for GTP by GEF is a rate limiting step in protein
      synthesis. The multisubunit characteristics of GEF suggest that this protein is
      composed of several distinct structural and functional domains, and is regulated
      by allosteric means and by phosphorylation. The activity of GEF may be regulated
      indirectly by the phosphorylation state of the smallest subunit of eIF-2 (alpha
      subunit). On the other hand, phosphorylation of the largest subunit of GEF (82-kD
      subunit) by casein kinase (CK) I or II stimulates GDP/GTP exchange. GEF contains
      NADPH which is required for structural integrity of the protein. Upon stimulation
      of cells by insulin and growth factors, allosteric activation of GEF by sugar
      phosphates and other effector molecules may also play an important role in the
      regulation of polypeptide chain initiation. In this article, recent information
      about structure-function relationship of eIF-2 and GEF in nucleotide exchange and
      the regulatory mechanisms that influence the rate of polypeptide chain initiation
      under various physiological and pathological conditions are presented.

PMID- 7581747
TI  - Properties of rat liver L-threonine deaminase.
AB  - We have studied several properties of rat liver L-threonine deaminase: (1) the
      affinity for the two substrates, L-serine and L-threonine; (2) the
      threonine/serine activity ratio which changes with increasing pH; (3) the
      activation, by pyridoxal 5'-phosphate which is linked to the nonprotonated form
      of the coenzyme and to at least an -SH group of the enzyme, and (4) the
      reactivation by pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate after
      dissociation of the coenzyme. The mechanism of the reactivation by pyridoxamine
      5'-phosphate is the most interesting problem opened by the present research.

PMID- 7581746
TI  - Carboxypeptidase A hydrolyses benzoylglycyl-histidyl-leucine but not
      furylacryloyl-phenylalanyl-glycyl-glycine, two usual substrates for angiotensin I
      converting enzyme.
AB  - We compared angiotensin I-converting enzyme (ACE) and carboxypeptidase A (CPA),
      two zinc metallopeptidases, for the hydrolysis of the usual ACE synthetic
      substrate benzoylglycyl-histidyl-leucine (HHL) investigating the possible
      interference by CPA in the determination of ACE activity in biological fluids.
      Both purified enzymes hydrolyse HHL in a radiochemical assay with the same
      optimal pH, a characteristic divalent metal requirement, a close similar behavior
      against inhibitors of other metallopeptidases, such as enkephalinase and kininase
      I, and the involvement of arginine and lysine residues in their active site.
      Conversely, CPA does not show the other catalytic properties of ACe, i.e.
      chloride dependence, low Km for HHL, inhibition by specific synthetic ACE
      inhibitors and antibody, also hydrolysis of the other ACE substrate
      furylacryloylphenylalanyl-glycyl-glycine (FAPGG). We advise the use of ACE
      inhibitors to validate ACE measurement with HHL or, alternatively, FAPGG, which
      is a more specific substrate for ACE, must be preferred, although the poor
      sensitivity of the spectrophotometric assay with this substrate limits its use to
      blood samples.

PMID- 7581748
TI  - S-acetyl- and S-phenylacetyl-glutathione as glutathione precursors in rat plasma
      and tissue preparations.
AB  - S-acetyl- and S-phenylacetyl-glutathione derivatives were synthesized by using a
      new procedure. The derivatives were incubated with rat plasma and red blood
      cells, and also with cytosol from rat liver, kidney and heart, or tissue slices
      from rat heart, kidney and liver. A limited hydrolysis of the compounds occurs in
      plasma, whereas hydrolysis occurs to a larger extent in tissue cytosols. Both
      purified and crude gamma-glutamyl-transpeptidase from different sources
      recognized the S-acetyl- and S-phenylacetyl derivatives as substrates.
      Intracellular glutathione increases after incubating the derivatives with red
      blood cells. A potential role of S-acetyl- and S-phenylacetyl-glutathione in
      replenishing cells with exogenous glutathione is envisaged.

PMID- 7581749
TI  - Prevention dollars and sense.

PMID- 7581751
TI  - Pediatricians' knowledge and attitudes concerning diagnosis and treatment of
      attention deficit and hyperactivity disorders. A national survey approach.
AB  - OBJECTIVE: To examine pediatricians' knowledge and attitudes concerning the
      diagnosis and treatment of attention deficit disorder (ADD) and attention-deficit
      hyperactivity disorders (ADHD). DESIGN: Cross-sectional survey. SETTING: United
      States. PARTICIPANTS: Three hundred eighty pediatricians comprising respondents
      from a random sample of 1000 members of the American Academy of Pediatrics.
      INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Pediatricians' perceptions of
      diagnostic modalities, child and family communication concerning ADD and ADHD
      diagnosis and treatment, and a variety of treatment issues were assessed in this
      study. Findings indicate that methylphenidate (Ritalin) hydrochloride is the most
      prescribed medication for treatment of ADD and ADHD. Pediatricians reported
      common parent and child misperceptions about ADD and ADHD treatment. Results
      suggest a wide range of reported physician behavior with respect to the diagnosis
      and treatment of ADD and ADHD. CONCLUSION: Greater attention could be paid to
      providing accurate information in medical and educator training with respect to
      the cause, diagnosis, and treatment of ADD and ADHD.

PMID- 7581752
TI  - Testing models predicting severity of respiratory syncytial virus infection on
      the PICNIC RSV database. Pediatric Investigators Collaborative Network on
      Infections in Canada.
AB  - OBJECTIVES: To determine the sensitivity and specificity of published prognostic
      models to predict morbidity resulting from lower respiratory tract disease caused
      by respiratory syncytial virus in an independent pediatric population and to
      assess the accuracy of single risk factors in predicting adverse outcome. DESIGN:
      All articles obtained from a MEDLINE search that used the terms prognosis or
      sequelae and respiratory syncytial virus, and from the references of these
      articles, were reviewed. Studies were included if risk factors and outcomes were
      defined and if information was available in a database of prospectively enrolled
      patients with respiratory syncytial virus infections. A probability of adverse
      outcome was assigned to each patient in the cohort using prognostic models
      described in the articles. A test was considered positive if the probability of
      the adverse outcome was 5% or more. PATIENTS: Six hundred eighty-nine patients
      hospitalized with respiratory syncytial virus in seven tertiary care centers
      across Canada were prospectively enrolled in the Pediatric Investigators
      Collaborative Network on Infections in Canada database. MAIN OUTCOME MEASURES:
      The sensitivity and specificity of single predictors and of models in predicting
      severe disease were determined. RESULTS: The sensitivity of single predictors
      varied from 17% to 46%. A model that used age and oxygen saturation at admission
      in previously well infants had a sensitivity of 98% and a specificity of 47% when
      predicting intensive care unit admission. Another model that included age at
      hospitalization, gestational age, presence of an underlying condition, and
      respiratory syncytial virus subtype used to predict the outcome of a high
      severity index had a sensitivity of 77% and a specificity of 76%. When the above
      model was modified by exclusion of viral subgroup, sensitivity increased to 94%,
      but specificity decreased to 46%. CONCLUSION: Previously described prognostic
      models were generalizable to an independent study population.

PMID- 7581753
TI  - School-based health care for urban minority junior high school students.
AB  - OBJECTIVE: To describe the use of school-based health clinics by urban minority
      junior high school students. DESIGN: Review of demographic and utilization data
      collected by service providers during clinic visits. SETTINGS AND PARTICIPANTS:
      Health clinics in four junior high schools that enrolled predominantly Hispanic
      students who were residing in an economically disadvantaged, medically
      underserved New York (NY) school district. RESULTS: Of 5757 students who were
      enrolled in the schools, 5296 (92%) obtained parental consent to use the clinics,
      and 3723 (65%) used the clinics during the 1991-1992 academic year. Clinic users
      were 11 to 15 years old, 50% male and 50% female, 81% Hispanic and 14% black, and
      29% sixth graders, 33% seventh graders, and 38% eighth graders. Clinic users made
      16,340 clinic visits during the 1991-1992 academic year. Presenting complaints
      were mental health problems (32%), illness (14%), injury (12%), physical
      examination (5%), immunization (3%), follow-up (21%), and other (13%). Referral
      sources were clinic outreach (48%), self (44%), and school personnel (8%).
      Disposition of visits was on-site treatment (92%), referral to an affiliated
      hospital (5%), and referral elsewhere (3%). Compared with a nationwide group of
      high school-based clinics that served predominantly black adolescents, these
      clinics provided more mental health care (31% vs 21%), similar illness/injury
      care (32% vs 30%), and less preventive (10% vs 24%) and
      reproductive/contraceptive (7% vs 12%) care. CONCLUSIONS: Junior high school
      based clinics can provide a wide range of primary and preventive health care
      services for large numbers of medically underserved youths. The provision of
      mental health services may fill a critical need among inner-city adolescents.
      Clinic outreach may be necessary to maximize utilization, especially among high
      risk students.

PMID- 7581750
TI  - Epidemiology of shopping cart-related injuries to children. An analysis of
      national data for 1990 to 1992.
AB  - OBJECTIVE: To describe the epidemiologic characteristics of shopping cart-related
      injuries among children in the United States. DESIGN: A retrospective analysis of
      data from the National Electronic Injury Surveillance System of the US Consumer
      Product Safety Commission for 1990 to 1992. RESULTS: An estimated 75,200 shopping
      cart-related injuries occurred in children younger than 15 years treated in US
      emergency departments during 1990 to 1992 (95% confidence interval, 57,500 to
      92,900). Children younger than 5 years were at highest risk, accounting for
      63,200 (84%) of the injuries. A 20% increase was observed in the number of
      injuries among 0- to 4-year-old children from 1990 to 1992. Fifty-three percent
      of injured children were male. The head and neck region was the most common
      anatomic site of injury, accounting for 74% of injuries among children younger
      than 15 years. An estimated 2000 children (2.7%) younger than 15 years required
      hospital admission (1.2% in 1990 compared with 3.5% in 1992). Children aged 0 to
      4 years accounted for 93% of these hospital admissions. Among 0- to 14-year-old
      children, fractures accounted for 45% of hospital admissions, followed by
      internal injury (22%) and concussion (17%). CONCLUSIONS: Injuries related to
      shopping carts are an important cause of pediatric morbidity, especially among
      children younger than 5 years. These injuries can also result in death. Shopping
      carts should be redesigned to decrease the risk of injury to children, and
      transportation of children in shopping carts of current design should be
      prohibited.

PMID- 7581756
TI  - Early identification, screening, and brief intervention for adolescent alcohol
      use.
AB  - The high prevalence of alcohol and other drug use by adolescents poses a
      significant threat to the wellness of youth. Whereas there has been a significant
      decrease in the reported prevalence of use for most illicit drugs, there has been
      relatively little change in the reported use of alcohol and tobacco, the two most
      common drugs of abuse. As such, alcohol remains the drug of choice for most
      adolescents. In 1993, 67% of eighth graders had tried alcohol in their lifetime,
      as had 81% of 10th graders and 87% of high school seniors. More than a quarter of
      eighth graders (26%) had used alcohol in the past month, as had 42% of 10th
      graders and 51% of high school seniors. Most disturbing is that, in all three
      grade levels, among those who had used alcohol in the past 30 days, half or more
      had had five or more drinks in a row at least once (13.5%, 23%, and 28%,
      respectively). Although only 1% of adolescents consider themselves to have a
      drinking problem, 23% have often driven after excessive drinking, 17% report
      problems in peer relationships because of drinking, and 10% have been criticized
      by a close friend for drinking.

PMID- 7581755
TI  - Severe complications of measles requiring intensive care in infants and young
      children.
AB  - OBJECTIVE: To evaluate the characteristics of severe complications of measles in
      patients admitted to a pediatric intensive care unit. DESIGN: Clinical
      description of a case series. SETTING: The Pediatric Intensive Care Unit of
      Soroka Medical Center, Beer-Sheva, Israel, during a measles epidemic. PATIENTS:
      Fifteen pediatric patients with measles requiring intensive care. RESULTS:
      Fifteen of 237 hospitalized children with measles required intensive care in the
      Pediatric Intensive Care Unit. Eleven patients were malnourished; none had been
      vaccinated for measles. All 15 patients required mechanical ventilation for
      pneumonia that had caused severe respiratory distress. Twelve of 15 patients were
      severely hypoxemic before intubation. Seven had a clinical syndrome consistent
      with adult respiratory distress syndrome. Other complications on admission to the
      intensive care unit included spontaneous pneumothorax in three patients, empyema
      in two, encephalopathy in seven, shock in three, sepsis in five, hypocalcemia in
      11, thrombocytopenia in eight, and coagulopathy in seven. Complications during
      treatment included pneumothorax in four patients, fibrosing alveolitis in one,
      brain infarct in one, thrombus formation in three, and nosocomial sepsis in one.
      Four patients had long-term sequelae (chronic lung disease, subacute sclerosing
      panencephalitis, hemiplegia, and partial amputation of a limb), and seven
      patients recovered uneventfully. Four patients died; all had adult respiratory
      distress syndrome, three had pneumothorax, and one had nosocomial sepsis.
      CONCLUSIONS: Patients with measles who require intensive care have a high risk
      for death or long-term complications, even when treated in a modern pediatric
      intensive care unit. Adult respiratory distress syndrome and air leaks were the
      most severe complications in these patients. To reduce the severity of these
      complications, mechanical ventilation should be based on using the lowest
      possible inspiratory pressure and fraction of inspired oxygen, while accepting an
      arterial oxygen pressure less than 60 mm Hg. Secondary bacteremia was an early
      and prominent complication, and antibiotic treatment should be instituted early
      in patients with measles requiring intensive care.

PMID- 7581754
TI  - The cost of comprehensive preventive medical services for adolescents.
AB  - OBJECTIVES: To address the need for clinical preventive services for 11- to 21
      year-old males and females and provide cost estimates for those services under a
      fee-for-service system. Preventive services include screening, health promotion,
      and immunizations. DESIGN: The prevalence of adolescent morbidities was derived
      from national surveys. Estimated costs of these morbidities were obtained from
      published data and adjusted for 1992 dollars using the Consumer Price Index. The
      estimated costs of preventive services for adolescents under a fee-for-service
      system were derived from a 1993 survey of nine Blue Cross and Blue Shield plans
      and four insurance companies. MAIN OUTCOME MEASURES: The cost of adolescent
      morbidities includes only direct medical costs for a single year and excludes
      long-term and indirect costs. The cost of clinical preventive services is
      calculated at 100% participation levels. RESULTS: Each year, an estimated $33.5
      billion is spent on medical treatment for select adolescent morbidities,
      approximately $859 per adolescent per year; this is a conservative estimate. The
      average cost of clinical preventive services per adolescent per year would be
      approximately $130 in a fee-for-service system, although these are not entirely
      "new" costs because payers already incur screening costs for some conditions.
      CONCLUSION: The cost-effectiveness of clinical interventions for various health
      risk behaviors among adolescents is unknown. It appears that preventive
      interventions would have to eliminate 15% of adolescent morbidities overall to
      break even in economic terms.

PMID- 7581758
TI  - Physical abuse among high school students. Prevalence and correlation with other
      health behaviors.
AB  - OBJECTIVE: To better understand the epidemiology of physical abuse among
      adolescents. DESIGN: School-based survey of students in grades 9 through 12.
      SETTING: Twenty-five schools throughout Oregon in 1993. MAIN OUTCOME MEASURES:
      Prevalence of ever being physically abused, prevalence of most recent occurrence
      of physical abuse, and correlation of physical abuse with high-risk health
      behaviors. RESULTS: Of the 1957 respondents, 31.5% reported having ever been
      physically abused, with female subjects (34.6%) more likely than male subjects
      (28.0%) to have ever been abused. Overall, 3.7% of students had been physically
      abused in the past week, 7.8% in the past month, and 16.3% in the past year.
      Based on multivariate models, students physically abused in the past year were
      more likely than students who had never been physically abused to engage in a
      variety of high-risk behaviors; these included weapon carrying (odds ratio, 1.9),
      suicidal ideation (odds ratio, 2.1), cigarette smoking (odds ratio, 1.8), cocaine
      use (odds ratio, 3.2), or multiple sexual partners (odds ratio, 1.9).
      CONCLUSIONS: Physical abuse, an important problem among high school students, is
      correlated with many high-risk behaviors. Using consistent definitions, periodic
      surveys of children about physical abuse and other types of violent behavior are
      needed to provide better estimates of the extent of these problems.

PMID- 7581757
TI  - Lipid intolerance in newborns is associated with hepatic dysfunction but not
      infection.
AB  - OBJECTIVE: To examine the hypothesis that fat intolerance in newborns who receive
      intravenous lipid is related to both infection and liver dysfunction. DESIGN:
      Prospective survey. SETTING: Tertiary intensive care nursery. PATIENTS: All
      newborns who were admitted to the neonatal intensive care unit during a 20-month
      period and received parenteral lipid for 2 or more weeks were eligible for the
      study. Of 279 newborns who received parenteral nutrition, 162 met eligibility
      criteria and form the basis of this report. INTERVENTIONS: None. MAIN OUTCOME
      MEASURE: Fat intolerance as defined by a serum triglyceride level of 1.69 mmol/L
      or greater (> or = 150 mg/dL). RESULTS: Triglyceride levels were similar in
      infected and noninfected patients. Newborns with hypertriglyceridemia were more
      likely to have liver dysfunction (P < .001) or growth retardation (P < .01), but
      not infections. Hypertriglyceridemia was approximately twice as likely (P < .05)
      in newborns with either growth retardation or liver dysfunction. CONCLUSIONS:
      Liver dysfunction and fetal growth retardation were associated with lipid
      intolerance in newborns who received intravenous fat. Infection does not appear
      to be independently associated with hypertriglyceridemia. In the absence of liver
      dysfunction or growth retardation, there is no a priori reason to limit
      intravenous lipid use in the presence of infection. Close monitoring of
      triglyceride levels with adjustments in lipid dose is warranted, especially in
      small, sick newborns who are at highest risk for hypertriglyceridemia.

PMID- 7581759
TI  - The role of pulse oximetry. Its use as an indicator of severe respiratory disease
      in Peruvian children living at sea level. Respiratory Group in Peru.
AB  - OBJECTIVE: To evaluate pulse oximetry as a technique for diagnosing pneumonic and
      nonpneumonic acute lower respiratory tract infection (ALRI) in Peruvian children.
      DESIGN: Children with acute respiratory infection were diagnosed with hypoxemia
      by pulse oximetry, with ALRI by the World Health Organization (WHO) algorithm and
      clinical examination, and with pneumonia by radiographic examination. Diagnoses
      were compared using kappa analysis. SETTING: Pediatric emergency department.
      PATIENTS: Peruvian pediatric patients with acute respiratory infection (n = 269)
      and well children (n = 162). MAIN OUTCOME MEASURES: Hypoxemia (arterial oxygen
      saturation < 96.6% of the mean arterial oxygen saturation of well children -2
      SD). RESULTS: Children with pneumonic and nonpneumonic ALRI (59%, 160/269) had a
      mean (+/- SD) arterial oxygen saturation significantly lower than well children
      (93.8% +/- 3.5% vs 98.7% +/- 1.51%; P < .01). Pulse oximetry detected 88% and the
      WHO algorithm 90% of cases of pneumonic ALRI. The WHO algorithm and pulse
      oximetry detected 72% of radiologic pneumonia. Pulse oximetry misclassified
      notably fewer well children than did the WHO algorithm (4% vs 35%). Pulse
      oximetry and the WHO algorithm together (SATWHO) detected 99% and 87% of
      pneumonic ALRI and radiologic pneumonias, respectively, and both methods detected
      94% of all cases of pneumonic and nonpneumonic ALRI diagnosed clinically.
      CONCLUSIONS: Pulse oximetry and the WHO algorithm are practical, helpful, and
      appropriate for use in developing countries to identify children with pneumonic
      and non-pneumonic ALRI who require treatment. The SATWHO is highly sensitive for
      detecting children with ALRI.

PMID- 7581760
TI  - Radiological case of the month. Inflammatory myofibroblastic tumor.

PMID- 7581761
TI  - Picture of the month. Acute hemorrhagic edema of infancy.

PMID- 7581762
TI  - Pathological case of the month. Cystinosis.

PMID- 7581763
TI  - The association of vision-threatening ocular injury with infant walker use.

PMID- 7581764
TI  - Home on the range: childhood lead exposure due to family occupation.

PMID- 7581765
TI  - Factors prompting referral for cardiology evaluation of heart murmurs in
      children.

PMID- 7581766
TI  - Noonan syndrome and neuroblastoma.

PMID- 7581768
TI  - Suture ligation of supernumerary digits and 'tags': an outmoded practice?

PMID- 7581767
TI  - Vitamin B12 deficiency associated with low breast-milk vitamin B12 concentration
      in an infant following maternal gastric bypass surgery.

PMID- 7581769
TI  - Signs and symptoms predicting acute otitis media.

PMID- 7581770
TI  - Symptoms and spontaneous passage of esophageal coins.

PMID- 7581772
TI  - Symptoms and spontaneous passage of esophageal coins.

PMID- 7581771
TI  - Symptoms and spontaneous passage of esophageal coins.

PMID- 7581773
TI  - Evaluations of children who have disclosed sexual abuse via facilitated
      communication.

PMID- 7581774
TI  - Evaluations of children who have disclosed sexual abuse via facilitated
      communication.

PMID- 7581775
TI  - [Lessons from Pierre Royer].

PMID- 7581776
TI  - [Polyunsaturated fatty acids and cerebral-sensory development in infants].

PMID- 7581777
TI  - [What are the criteria for the choice of future professors of pediatrics?].

PMID- 7581778
TI  - [Retrospective analysis of 1331 samples of cerebrospinal fluid in newborn infants
      with suspected infection].
AB  - BACKGROUND: Definitive diagnosis of a neonatal infection usually requires
      recovery of an etiologic agent from body fluids or tissues such as spinal fluid,
      blood and urine. Routine lumbar puncture (LP) may raise some problems in
      interpreting results. POPULATION AND METHODS: A retrospective analysis of 1331
      samples of CSF was made. LP had been performed on 1041 neonates including 569
      prematures (54.6%) as a part of the evaluation for suspected bacterial infection.
      RESULTS: In 50.7% of the cases, the CSF was haemorrhagic. The frequency of
      traumatic taps increased with the degree of prematurity, low birth weight,
      precocity of LP, association with respiratory distress and disorders of
      coagulating factors. In addition, haemorragic taps modified biochemical and
      cytologic characteristics of CSF. One hundred and six (8%) CSF samples contained
      organisms but the diagnosis of meningitis was certain in only 23 cases (2.2%). In
      the other 83 cases, CSF was thought to be contaminated, mostly by coagulase
      negative staphylococci. Since both blood and CSF cultures were positive for the
      same bacterial organism in 18 cases, it was concluded that the LP had been useful
      in identifying the pathogens in only five cases. The high frequency of
      contaminated CSF led to overestimation of the incidence of true bacterial
      meningitis (0.57% in our study). CONCLUSIONS: The low incidence of meningitis in
      neonates, the risk of having an haemorragic tap associated with the possibility
      of clinical aggravation during LP and the fact that the same pathogen is
      frequently (78.2% of cases) identified in blood cultures suggest that the
      immediate and routine LP is of less value than expected in infants suspected to
      be infected. LP could be postponed when the neonate presents with a respiratory
      distress syndrome and/or a precarious haemodynamic state.

PMID- 7581779
TI  - [Evaluation of the psychosocial care in maternity: experience at the Poitiers
      University Hospital].
AB  - BACKGROUND: High psychosocial risk pregnancies require specialized
      multidisciplinary help and follow-up in order to improve the outcome of babies.
      POPULATION AND METHODS: Thirty pregnancies were selected among 3500 and followed
      by a multidisciplinary team during 1990 and 1991. Evaluation included risk
      predictors, neurodevelopmental outcome of children at 9 and 24 months, number and
      time of judicial notifications. Evaluation of the mother-to-baby relationship by
      a psychologist as well as the environmental variables were performed. RESULTS:
      Four families had one or two, 20 families three or five and six families, six or
      more of the 15 risk predictors studied. Over the babies followed-up until the age
      of 24 months, four were placed out of the family, three hospitalizations were
      medically unjustified and there was no hospitalization for child abuse or
      neglect. Twelve children had development delay and two developed an environmental
      related staturo-ponderal delay. Judicial notifications were realized 18 times
      during pregnancy or just after delivery and six times during the follow-up for
      child abuse and neglect. CONCLUSIONS: Taking care of high psychosocial risk
      pregnancies could be improved in special hospitalization units for mother and
      child. A better awareness of this problem could also improve the outcome of
      children, which remains very alarming.

PMID- 7581780
TI  - [Use of intravenous midazolam in status epilepticus in children].
AB  - BACKGROUND: Status epilepticus is usually treated by benzodiazepines such as
      diazepam or clonazepam in association with phenytoin and phenobarbital. Midazolam
      (MDZ) is a recently developed short-elimination half-life benzodiazepine. CASE
      REPORTS: Four children, aged 3 days to 4 years, were hospitalized in the
      pediatric intensive care unit for life-threatening illness and developed status
      epilepticus. They were given an i.v. bolus dose of 300 to 500 micrograms/kg of
      MDZ immediately followed by a continuous i.v. infusion at the dose of 100 to 300
      micrograms/kg/h. All seizures stopped within 1 hour after the bolus dose
      administration. No acute adverse events of MDZ were noted. Withdrawal symptoms in
      one patient were controlled by progressive reduction of MDZ doses. Neurologic
      sequelae were noted in three children, secondary to their primitive illness.
      CONCLUSIONS: High doses of MDZ are effective for treating refractory status
      epilepticus; optimal dosage and duration of treatment remains to be determined.

PMID- 7581782
TI  - [Deep granuloma annulare in children].
AB  - BACKGROUND: The granuloma annulare is a common benign disorder in childhood which
      may be difficult to recognize in its atypical forms, like deep granuloma
      annulare. CASES REPORT: Case 1: A 5-year-old girl suffered from subcutaneous
      nodules occurring on her soles. Open biopsy at the age of 6 years showed typical
      features of granuloma annulare. These nodules were still present one year later.
      Case 2: A 2-year-old girl suffered from nodular lesions on the anterior aspect of
      the lower legs similar to erythema nodosum with spontaneous outbreaks over 6
      months. Histological examination showed typical features of granuloma annulare.
      CONCLUSIONS: Diagnosis of the deep granuloma annulare is often difficult. Its
      relation with rheumatic nodules which have similar histological patterns is
      discussed.

PMID- 7581783
TI  - [Chronic septic granulomatosis revealed by neonatal pulmonary aspergillosis].
AB  - BACKGROUND: Pulmonary aspergillosis is now the main cause of death in chronic
      granulomatous disease (CGD); it may occur before the age of one year and then
      often reveals CGD. CASE REPORT: A male newborn was referred to hospital at 27
      days of age for fever (39 degrees C), hemodynamic failure and biological
      inflammation syndrome caused by pulmonary infection. Chest CT scan revealed
      multiple and bilateral intraparenchymatous nodules. An open lung biopsy showed
      histiocystic granuloma with multinucleated giant cells. Culture of tracheal,
      bronchoalveolar lavage samples and lung biopsy grew positive for Aspergillus
      fumigatus. Impaired chemiluminescence production by neutrophils was detected,
      enabling the diagnosis of CGD. It was later confirmed by the study of neutrophils
      functions. The child recovered after 12 months of parenteral amphotericin B
      therapy. CONCLUSION: A febrile multifocal pneumopathy occurring in infancy should
      lead to consider the possibility of CGD which may be confirmed by the
      chemiluminescence test.

PMID- 7581781
TI  - [Zincemia, cupremia and infection in malnourished children].
AB  - BACKGROUND: Serum copper and zinc levels are decreased in malnourished and
      infected children. The role of either malnutrition or infection remains
      undetermined. POPULATION AND METHODS: Serum zinc and copper concentrations were
      measured by atomic absorption spectrophotometry in 31 malnourished infants aged 1
      to 26 months and 28 eutrophic infants aged 3 to 22 months. Fourteen infants of
      the first group and 10 of the second were infected at the time of study. RESULTS:
      Serum zinc and copper levels were significantly decreased in infants with
      malnutrition (zinc: 66 +/- 32 micrograms/dl and copper: 81 +/- 51 micrograms/dl
      versus 108 +/- 26 and 185 +/- 21, respectively, in eutrophic infants) (p <
      0.001). These levels were still lower in those malnourished infants who were
      infected (zinc: 49.5 +/- 18 micrograms/dl and copper: 63.5 +/- 37 micrograms/dl
      versus 81.56 +/- 35 and 94 +/- 56 in non infected patients) (p < 0.02).
      CONCLUSIONS: Infection increases the risk of low serum zinc and copper
      concentrations seen in malnourished children. This factor must be taken in
      account when treating malnutrition.

PMID- 7581784
TI  - [Rothmund-Thomson syndrome and osteosarcoma].
AB  - BACKGROUND: The Rothmund-Thomson syndrome is a hereditary dermatosis frequently
      accompanied by less well-known non dermatologic features including osteogenic
      sarcoma. CASE REPORT: A girl developed the classical dermatologic features of the
      Rothmund-Thomson syndrome since the first months of life. When she was 6 years
      old, she suffered from painful limitation of motion of her left leg. X-rays, MNR
      imaging and bone scintigraphy showed typical features of osteosarcoma of the
      distal portion of the femur. Diagnosis was confirmed by histologic examination
      through open biopsy. The search for metastatic lesions was negative. The patient
      was given chemotherapy and the tumor was resected 45 days later followed by
      postoperative chemotherapy. CONCLUSION: About 12 similar cases of osteosarcoma
      have been reported in patients with the Rothmund-Thomson syndrome. A review of
      literature allows to recognize some peculiar features of such association.

PMID- 7581785
TI  - [Water intoxication following preparation for barium enema].
AB  - BACKGROUND: Induction of water intoxication from tap water enemas was reported a
      few years ago. Its treatment is still debated. CASE REPORT: A 4 1/2 year-old boy
      was admitted because he suffered from coma grade I. A barium enema had been
      prescribed for fecal incontinence and the patient had been given orally about 4
      liters of water during the 24 hours preceding this investigation. Blood
      examination showed;: Na 122 mEq/l; K 3 mEq/l; Cl 87 mEq/l. Brain CT scan was
      normal. The patient was placed under restriction of fluid and was given i.v. 5.8%
      NaCl solution (2 mM/kg) for 3 hours. Convulsions appeared despite this treatment
      requiring intubation and ventilation plus increasing doses of NaCl: 20% solution
      (2 mM/kg) for 30 minutes followed by 2 mM/kg for 3 hours, associated with
      mannitol and furosemide infusion. CONCLUSION: Use of hypertonic saline solutions
      in the treatment of water intoxication is discussed. Acute hyponatremia must be
      rapidly corrected using hypertonic saline solution plus restriction of fluid and
      diuretic.

PMID- 7581786
TI  - [Therapeutic compliance in adolescents with chronic disease].
AB  - In clinical practice, non-compliance is an often unrecognised or frustrating
      reality, which physicians find difficult to accept or deal with. Possible
      determinants of adolescents' level of compliance may be divided into demographic
      factors, patient and family characteristics, aspects of the illness and treatment
      regimen, and quality of the patient-doctor relationship. Compliance should be
      viewed as a reflexion of the experience of chronic illness as well as the
      expression of specific adolescent developmental issues. Practical guidelines are
      proposed.

PMID- 7581790
TI  - [Radiologic case of the month. Obstruction of the anterior urethra by calculus in
      oxalosis].

PMID- 7581788
TI  - [Lead poisoning in children: from epidemiology to public health].
AB  - Epidemiological research has provided a better knowledge of lead poisoning
      effects on neuro-cognitive development of children. The increased sensitivity of
      screening biological tests and the decrease of the therapeutic threshold of
      intervention make primary prevention even more necessary. The oral route being
      responsible for the most severe morbidity of lead poisoning in children,
      screening must first specify the risk factors associated with oral lead
      absorption according to the age of children and local exposure to sources of
      lead.

PMID- 7581787
TI  - [Treatment of atopic dermatitis].
AB  - There are three components in the treatment of atopic dermatitis: 1) a general
      treatment (mainly antibiotherapy directed towards Staphylococcus aureus during
      acute phases), 2) local treatment (local antiseptics, local steroids,
      emollients), 3) practical advice. In addition, it is of great importance that
      clear and complete information on the illness should be given to the parents.

PMID- 7581791
TI  - [Treatment by oral route of urinary tract infections in children].

PMID- 7581792
TI  - [Recurrent acute intestinal intussusception].

PMID- 7581789
TI  - [The pediatrician and the telephone].
AB  - Approximately half of the phone calls received in the pediatrician's office are
      telephone consultations or advice requests concerning pathologies. In those cases
      the pediatrician has to know that his responsibility is involved. Among the rules
      to be applied in this telephone practice, he must always require that the child
      be examined when parents call for the second time. In some chronic pathologies
      permanent phone services with the participation of trained practitioners might be
      useful in order to properly answer parent's advice requests.

PMID- 7581793
TI  - [Breast feeding in Togo].

PMID- 7581794
TI  - [Etiologic and therapeutic aspects of ingestion of caustic substances].

PMID- 7581798
TI  - [The action of laser radiation on thymic hormone production].
AB  - Irradiation of the epithelial cells from human thymus (cell line HTSC) by arsenid
      gallium laser (0.89 nm, 1500 Hz) induces an enhancement of thymic hormone
      production. The concentration of alpha-1-thymosin was substantially increased on
      the days 1 and 5 in culture after irradiation. The increase of thymulin level in
      cultural supernatants was less pronounced and displayed after irradiation during
      3-4 minutes. Local laser irradiation of thymus region of rats (5 minutes, 10
      times) induce the increase of serum concentration of alpha-1-thymosin and the
      decrease of serum level of thymulin 2 days after irradiation.

PMID- 7581797
TI  - [Disordered thymus function and endocrine control as one of the bases for the
      development of a late postradiation immunodeficiency (a review of the
      literature)].
AB  - The review is devoted to the analysis of 155 reference published mainly in the
      recent years, which deal with the radiation effects on immune, nervous and
      endocrine systems. The role of thymus in the late manifestations of postradiation
      immunodeficiency is discussed. The published data on immune system disturbances
      and postradiation disfunction of endocrine system in the persons who suffered
      from the Chernobyl accident are considered.

PMID- 7581795
TI  - [Ileal perforation with CMV enteritis in a newborn infant with acquired
      immunodeficiency syndrome].

PMID- 7581796
TI  - [A stochastic model of induced genome instability].
AB  - It was proposed a stochastic model of induced instability of genome based on the
      analysis of the present theoretical views and experimental data. The principles
      for the choice of the model of optimum complexity are discussed. Proposed
      approach may be used for remote genetical consequences of irradiation.

PMID- 7581800
TI  - [The effect of ionizing radiation and physical loading on the molecular
      heterogeneity of nucleoside phosphate kinases in liver subcellular fractions].
AB  - The different molecular forms of nucleoside-monophosphate kinases (KF 2.7.4.4)
      and nucleoside-diphosphate kinases (KF 1.7.4.6) which are responsible for the
      final steps of pyrimidine nucleotide synthesis were determined in mitochondrial
      rat hepatic supernatant under condition of combined influence of X-ray and
      maximum physical exercises (running up to complete exhaustion). The maximum
      activity of investigated nucleosidediphosphate kinases were observed in intact
      animals in that fractions which were eluted with tris-HCl buffer solution (0.075
      and 1.0 M, pH 7.4). X-ray radiation and physical exercises caused the deviation
      of chromatographic data of maximal enzymatic activities. The drastic lowering of
      investigated enzymes was observed after X-ray irradiation and maximum physical
      exhaustion. This fact is in favour for the suppression of the final steps of
      primidine nucleotides synthesis under explored conditions of experimental
      investigations.

PMID- 7581801
TI  - [The effect of antioxidants on functional brain disorders caused by low-intensity
      ionizing radiation].
AB  - The effects of daily intraperitoneal injections of alpha-tocopherol (30 mg/kg per
      day) and synthetic antioxidant IHFAN-30 (30 mg/day) in rats were compared during
      low-level ionizing radiation (10 days, dose rate 5 mGy/h, total dose 1.2 Gy).
      There were analysed: (1) amplitude of population spike of hippocampal slices; (2)
      endogenous phosphorylation in vitro of hippocampal synaptic proteins in the
      presence of cAMP; (3) formation, manifestation and reduction of food-procuring
      reflex. The findings showed that antioxidants made some correction of the
      functional state of hippocampal slices and cAMP-dependent phosphorylation system
      activity in brain cells from irradiated animals. No influence on training and
      memory functions was detected.

PMID- 7581802
TI  - [The property of radiation in low doses and of low-intensity ionizing radiation
      to cause metallothionein induction].
AB  - The effect of the increase in metallothionein content in hepatocytes of white
      mice located in conditions of chronic low dose rate and low-dose irradiation. In
      this work an opportunity of participation of metallothioneins, as the natural
      radioprotector and factor of nonspecific resistance, in adaptation of organisms
      to adverse environmental conditions was discussed.

PMID- 7581803
TI  - [Changes in the nucleolar characteristics in fish embryo cells under the action
      of low doses of radiation].
AB  - The nucleolus activity of fish embryo cells was stimulated by low-level radiation
      at a dose rate of 2-13 mGy/h. The size of nucleoli generally increased in embryos
      of Cyprinus carpio, whereas the number of nucleoli was greater in embryos of
      Carassius auratus gibelio. The higher the functional activity of nucleolus is,
      the more pronounced are changes in the characteristics. The size of single
      nucleolus at gastrulation is the most sensitive characteristic.

PMID- 7581799
TI  - [The effect of the local irradiation of areas of the thymus,
      hypothalamus/hypophysis and gonads in mice on the cellularity of the autologous
      and transplanted thymus].
AB  - Mice were grafted with syngeneic neonatal thymus 1-3 days or 7.5-8 months after
      local irradiation of thymus, hypothalamus/hypophysis and gonads. Thymus weight
      and thymocyte number were measured in autologous and grafted thymus 35-40 days
      after the transplantation. Thymus transplantation induces significant decrease in
      weight and cellularity of both autologous and grafted thymus. Irradiation of
      autologous and grafted thymus in doses of 1 and 10 Gy abrogates this effect.
      Irradiation of hypothalamus/hypophysis and gonads induces decrease of weight and
      cellularity of autologous and grafted thymus. Irradiation of gonads does not
      abrogate inhibitory effect of thymus transplantation. Local irradiation of all
      three regions decreases titre of serum thymic activity and influence
      concentrations of some hypophysis and adrenal hormones.

PMID- 7581804
TI  - [The effect of different classes of radioprotectors on the survival of mice
      irradiated at a wide range of doses].
AB  - In experiments with mice three kinds of dose dependence of radioprotection
      efficiency were shown for different radioprotectors. Maximum protection was
      revealed in the ranges of LD70-100/30 for naphthyzin and cystamine, LD50-70/30
      for thymogen and lymphokinin, LD70/30 for prodigiosan and polyribonate. The
      necessity of research of preparations which increase radioresistance in the wide
      range of doses is pointed. The problem of improved criteria for radioprotector
      selection is discussed.

PMID- 7581806
TI  - [The sequelae of the Kyshtym and Chernobyl accidents for hydrobionts].
AB  - The results of the works, published in the USSR and the CIS, on studies of the
      action of radioactive pollution upon hydrobionts in natural conditions were
      summarized and analyzed. Feasible causes of discrepancy of obtained data were
      considered.

PMID- 7581805
TI  - [The effect of the potential antiradiation agent compound HC-1539 on reparative
      DNA synthesis induced by the damaging action of the chemical mutagen N-nitroso-N
      methylurea and radiation].
AB  - The influence of NS-1539, a potential anti-irradiation agent and indole analogues
      of tamoxifen on the DNA repair synthesis in the bone marrow and lymphocytes of
      peripheral blood was studied. It was found that the DNA repair processes from
      damages caused by chemical mutagen N-nitroso-N-methylurea or physical factor UV
      irradiation in the bone marrow cells after the NS-1539 protection of mice as well
      as in lymphocytes of peripheral blood of human donors were enhanced. The
      enhancing of DNA repair synthesis was seen not earlier than 18 hours after the NS
      1539 injection to mice in vivo or when NS-1539 was added to lymphocyte suspension
      in vitro and observed up to the third day. This period of time coincides with the
      time of formation of radioresistance of organism under the influence of this
      agent as well as with the time of realization effects of steroid hormones on
      target cells.

PMID- 7581807
TI  - [A quantitative morphological study of the blood system in the common field mouse
      and the red-backed vole living in the area of the eastern Urals radioactive
      trace].
AB  - A number of quantitative morphological indices of blood system of two mice-like
      rodent species caught in radioactive contaminated areas was studied. Certain
      deviation in haemopoiesis and in blood characteristics were noted. The degree of
      deviations was not similar in the species with different radiosensitivity. It
      depends most probably on the total effect of the factors influenced animals in
      surroundings.

PMID- 7581809
TI  - Expired hydrocarbons in patients with acute myocardial infarction.
AB  - Pentane and isoprene concentrations were analyzed in single end-expiratory breath
      samples using gas chromatography. Breath analysis was performed in 15 patients
      with acute myocardial infarction, 15 patients with stable angina, and 15 healthy
      control subjects. The two patient groups were well matched for age, sex, smoking
      habits, hypertension and serum cholesterol levels. There was no significant
      difference in breath pentane concentration in the acute myocardial infarction
      group (0.29 +/- 0.03 nmol/l) (mean +/- SEM) compared to the group with stable
      angina (0.31 +/- 0.03 nmol/l) or the control group (0.36 +/- 0.04 nmol/l).
      However, breath isoprene concentration was higher (p < 0.01) in the acute
      myocardial infarction group (11.4 +/- 1.2 nmol/l), compared to both the stable
      angina group (7.7 +/- 0.5 nmol/l) and the control group (7.1 +/- 1.0 nmol/l).
      There was no difference in either the pentane or isoprene concentrations between
      the control group and the group with stable angina. Since pentane is thought to
      be an index of lipid peroxidation, the results do not support the presence of
      enhanced lipid peroxidation in acute myocardial infarction in the absence of
      thrombolytic therapy or primary angioplasty. The mechanism responsible for
      isoprene elevation in acute myocardial infarction is unknown.

PMID- 7581808
TI  - Singlet oxygen-trapping reaction as a method of (1)O2 detection: role of some
      reducing agents.
AB  - The production of singlet oxygen by H2O2 disproportionation and via the oxidation
      of H2O2 by NaOCl in a neutral medium was monitored by spin trapping with 2,2,6,6
      tetramethyl-4-piperidone (TMPone). The singlet oxygen formed in both reactions
      oxidized 2,2,6,6 tetramethyl-4-piperidone to give nitroxide radicals. However the
      production of nitroxide radicals was relatively small considering the
      concentrations of H2O2 and NaOCl used in the reaction systems. Addition of
      electron donating agents: ascorbate, Fe2+ and desferrioxamine leads to an
      increase in the production of nitroxide radicals. We assumed that a very slow
      step of the reaction sequence, the homolytic breaking of the O-O bond of N
      hydroperoxide (formed as an intermediate product during the reaction of 1O2 with
      TMPone) could be responsible for the relatively small production of nitroxide
      radicals. Electron donating agents added to the reaction system probably raise
      the rate of the hydroperoxide decomposition by allowing a more rapid heterolytic
      cleavage of the O-O bond leading to a greater production of nitroxide radicals.
      The largest effect was observed in the presence of desferrioxamine. Its
      participation in this process is proved by the concomitant appearance of
      desferrioxamine nitroxide radicals. The results obtained demonstrate that the
      method proposed by several authors and tested in this study to detect singlet
      oxygen is not convenient for precise quantitative studies. The reactivity of
      TMPone towards O2.-/HO2. and .OH has been also investigated. It has been found
      that both O2.-/HO2. and .OH radicals formed in a phosphate buffer solution (pH
      7.4, 37 degrees C), respectively by a xanthine-oxidase/hypoxanthine system and
      via H2O2 UV irradiation, do not oxidize 2,2,6,6 tetramethyl-4-piperidone to
      nitroxide radicals.

PMID- 7581811
TI  - Oxidation of low density lipoprotein upon sequential exposure to copper ions.
AB  - Copper-induced LDL oxidation is characterized by an 'induction phase' (lag phase)
      during which the endogenous antioxidants are consumed, followed by a 'propagation
      phase' in which the LDL-associated polyunsaturated fatty acids are oxidized.
      Oxidation products may play an important role in the propagation of the oxidative
      process in the arterial intima as they increase the permeability of the damaged
      endothelium to various plasma components, including LDL. We therefore found it of
      interest to investigate the kinetics of LDL oxidation in vitro under conditions
      where LDL is sequentially exposed to Cu(2+)-induced oxidation. The results of our
      studies demonstrate that when native LDL is exposed to copper oxidation in a
      medium containing oxidized LDL, oxidation of the added LDL may be almost
      instantaneous. Furthermore, even when native LDL is added to 'oxidizing LDL'
      towards the end of the lag phase or during the propagation phase it becomes
      oxidized after a very short lag. This oxidation process, occurring in spite of
      the possible protective effect of the antioxidants present in the newly added
      LDL, indicates that although antioxidants prolong the latency period by
      preventing the formation of active free radicals, when such radicals are present
      in the system, oxidation propagates. These results lend strong support to the
      generally accepted paradigm regarding the mechanism of propagation of lipid
      oxidation. In view of the effect of oxidation products on the permeability of the
      endothelium, the observed shortening of the lag period may result in a vicious
      cycle, independent of the LDL-associated antioxidants, leading to continuing
      oxidation and foam cell formation.

PMID- 7581812
TI  - Kinetic modelling of in vitro lipid peroxidation experiments--'low level'
      validation of a model of in vivo lipid peroxidation.
AB  - Kinetic modelling overcomes some of the drawbacks of purely intuitive thinking in
      integrating information accumulated on chemical reactions involved in oxidative
      stress. However, it is important to assess if current knowledge about the
      reactions that mediate lipid peroxidation already allows satisfactory modelling
      of this process in near-to-physiological conditions. In this paper, a set of
      increasingly complex in vitro experiments on antioxidants (alpha-tocopherol and
      ascorbate) and lipid peroxidation in heterogeneous systems is simulated.
      Quantitative to semiquantitative agreement is found between experimental and
      simulation results. In addition, this theoretical analysis provided useful
      insights, suggested new hypotheses and experiments and pointed out relevant
      aspects needing further research. The results encourage and serve as partial
      validation for the formulation of relatively detailed mathematical models of in
      vivo lipid peroxidation. Some important aspects of the formulation and analysis
      of such models are discussed.

PMID- 7581814
TI  - Do EPR spectra show the presence of a unique and ubiquitous quinone-derived free
      radical that is associated with senescence in plants?

PMID- 7581810
TI  - 7,8 Dihydroneopterin inhibits low density lipoprotein oxidation in vitro.
      Evidence that this macrophage secreted pteridine is an anti-oxidant.
AB  - Neopterin and its reduced form, 7,8 dihydroneopterin are pteridines released from
      macrophages and monocytes when stimulated with interferon gamma in vivo. The
      function of this response is unknown though there is an enormous amount of
      information available on the use of these compounds as clinical markers of
      monocyte/macrophage activation. We have found that in vitro 7,8-dihydroneopterin
      dramatically increases, in a dose dependent manner, the lag time of low density
      lipoprotein oxidation mediated by Cu++ ions or the peroxyl radical generator 2,2'
      azobis (2-amidino propane) dihydrochloride (AAPH). 7,8-Dihydroneopterin also
      inhibits AAPH mediated oxidation of linoleate. The kinetic of the inhibition
      suggests that 7,8-dihydroneopterin is a potent chain breaking antioxidant which
      functions by scavenging lipid peroxyl radicals. No anti-oxidant activity was
      observed in any of the oxidation systems studied with the related compounds
      neopterin and pterin.

PMID- 7581813
TI  - Mangostin inhibits the oxidative modification of human low density lipoprotein.
AB  - The oxidation of low density lipoprotein (LDL) may play an important role in
      atherosclerosis. We investigated the possible antioxidant effects of mangostin,
      isolated from Garcinia mangostana, on metal ion dependent (Cu2+) and independent
      (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the
      lagtime to both metal ion dependent and independent oxidation of LDL in a dose
      dependent manner over 5 to 50 microM as monitored by the formation of conjugated
      dienes at 234 nm (P < 0.001). There was no significant effect of mangostin on the
      rate at which conjugated dienes were formed in the uninhibited phase of
      oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL
      were measured 4 and 24 hours after oxidation with 5 microM Cu2+ in the presence
      or absence of 50 microM or 100 microM mangostin. We observed an inhibition of
      TBARS formation with 100 microM mangostin at 4 hours (P = 0.027) but not at 24
      hours (P = 0.163). Similar results were observed in the presence of 50 microM
      mangostin. Mangostin, at 100 microM, retarded the relative electrophoretic
      mobility of LDL at both 4 and 24 hours after Cu2+ induced oxidation. Mangostin
      (100 microM) significantly inhibited the consumption of alpha-tocopherol in the
      LDL during Cu2+ initiated oxidation over a 75 minute period (P < 0.001). From
      these results, we conclude that mangostin is acting as a free radical scavenger
      to protect the LDL from oxidative damage in this in vitro system.

PMID- 7581815
TI  - Hyperbaric oxygen treatment attenuates glutathione depletion and improves
      metabolic restitution in postischemic skeletal muscle.
AB  - Glutathione serves as an important intracellular defence against reactive oxygen
      metabolites and has been shown to be depleted from a number of tissues upon
      oxidative stress. In the present study we have investigated the levels of total
      glutathione (reduced + oxidized) in skeletal muscle of the rat after prolonged
      ischemia and reperfusion with and without treatment with hyperbaric oxygen (HBO)
      for the initial 45 minutes immediately following reperfusion. A tourniquet model
      for temporary, total ischemia was used, in which one hind leg was made ischemic
      for 3 or 4 hours. Muscle biopsies were taken after 5 hours of reperfusion. In
      postischemic muscle there was a significant decrease of total glutathione
      compared to control muscle, but in the 3-hour-ischemia-groups the loss of total
      glutathione was less in HBO treated animals than in untreated. HBO treatment also
      preserved ATP and PCr and decreased edema formation in the postischemic muscle
      following 3 hours of ischemia and reperfusion when compared to untreated animals.
      However, after 4 hours of ischemia, HBO treatment failed to improve any of these
      parameters in the postischemic muscle. Thus, our results demonstrate that HBO
      treatment lessens the metabolic, ischemic derangements and improves recovery in
      postischemic muscle after 3 hours of ischemia followed by reperfusion.

PMID- 7581816
TI  - Release of hydrogen peroxide from human T cell lines and normal lymphocytes co
      infected with HIV-1 and mycoplasma.
AB  - Human T-cell lines and normal lymphocytes persistently or acutely co-infected
      with the human immunodeficiency virus type 1 (HIV-1) and mycoplasmas were found
      to release hydrogen peroxide (H2O2), a likely cause of oxidative stress in these
      cells. The spectrofluorometric measurement of H2O2 release from these cells,
      using the scopoletin fluorescence quenching technique, gave values of 16-84 p
      moles/10(6) cells/min. In CEM cells, H2O2 was released only when acutely co
      infected with HIV-1 and mycoplasmas, and not when infected with either organism
      alone. Anti-mycoplasmal antibiotics strongly reduced H2O2 release, and improved
      cell viability without blocking virus replication. These results suggest that the
      simultaneous infection by HIV-1 and mycoplasma leads to the release of H2O2, a
      toxic and potentially lethal metabolite, which in vivo may contribute to HIV-1
      pathogenicity.

PMID- 7581817
TI  - Induction of arthritis in mice and rats by potassium peroxochromate and
      assessment of disease activity by whole blood chemiluminescence and
      99mpertechnetate-imaging.
AB  - Arthritis develops in DBA/1xB10A(4R) mice and Wistar rats upon intraplantar
      injection of potassium peroxochromate (K3CrO8), and is here quantified by whole
      blood chemiluminescence (CL) and 99mpertechnetate-imaging (99mTcO4-), and related
      to overt disease symptoms (the arthritis index). During the aqueous decay of
      K3CrO8 to chromate (VI), the chromium(V)-bound oxygen is released as superoxide,
      hydroxyl radicals, singlet oxygen and hydrogen peroxide, the same reactants,
      which are produced by activated phagocytes during inflammation. Reactive oxygen
      species (ROS) trigger the breakdown of the sulfhydryl-dependent antioxidant
      defence system and induce the nuclear factor kappa B-dependent expression of pro
      inflammatory cytokines, which prime phagocytic NADPH oxidases to the enhanced
      production of ROS. During both the acute inflammatory response and the onset of
      the secondary response in non-injected paws, the phorbolester-stimulated ROS
      production of phagocytes was significantly enhanced (p < 0.001) and correlated
      well to the arthritis index (r = 0.797) and the uptake of 99mTcO4- into inflamed
      joints. Chromate(VI), formed during the decay of K3CrO8, contributes to the
      progression of arthritis by inhibition of glutathione reductase, thereby
      increasing intracellular H2O2 concentrations. In addition, Cr(VI) reduced to
      Cr(V) by ascorbate, catalyzes hydroxyl radical production in the presence of
      hydrogen peroxide. A stable loop forms, in which ROS, continuously produced by
      Cr(VI)/Cr(V) redox-cycling, drive the primary response into chronic self
      perpetuating inflammation. We see the main application of K3CrO8-induced
      arthritis and its assessment by both 99mTcO4- imaging and chemiluminescent
      immunosensoring of phagocytic activity in unseparated blood as for the rapid
      screening of novel anti-rheumatic drugs and treatments.

PMID- 7581818
TI  - Kinetics of the competitive degradation of deoxyribose and other molecules by
      hydroxyl radicals produced by the Fenton reaction in the presence of ascorbic
      acid.
AB  - The competition method in which the Fenton reaction is employed as an .OH radical
      generator and deoxyribose as a detecting molecule, has been used to determine the
      rate constants for reactions of the .OH radical with its scavengers. Nonlinear
      competition plots were obtained for those scavengers which reacted with the
      Fenton reagents (Fe2+ or H2O2). Ascorbic acid is believed to overcome this
      problem. We have investigated the kinetics of deoxyribose degradation by .OH
      radicals generated by the Fenton reaction in the presence of ascorbic acid, and
      observed that the inclusion of ascorbic acid in the Fenton system greatly
      increased the rate of .OH radical generation. As a result, the interaction
      between some scavengers and the Fenton reagents became negligeable and linear
      competition plots of A degree/A vs scavenger concentrations were obtained. The
      effects of experimental conditions such as, the concentrations of ascorbic acid,
      deoxyribose, H2O2 and Fe(2+)-EDTA, the EDTA/Fe2+ ratio as well as the incubation
      time, on the deoxyribose degradation and the determination of the rate constant
      for mercaptoethanol chosen as a reference compound were studied. The small
      standard error, (6.76 +/- 0.21) x 10(9) M-1s-1, observed for the rate constant
      values for mercaptoethanol determined under 13 different experimental conditions,
      indicates the latter did not influence the rate constant determination. This is
      in fact assured by introducing a term, kx, into the kinetic equation. This term
      represents the rate of .OH reactions with other reagents such as ascorbic acid,
      Fe(2+)-EDTA, H2O2 etc. The agreement of the rate constants obtained in this work
      with that determined by pulse radiolysis techniques for cysteine, thiourea and
      many other scavengers, suggests that this simple competition method is applicable
      to a wide range of compounds, including those which react with the Fenton
      reagents and those whose solubility in water is low.

PMID- 7581819
TI  - Increase in antilipoperoxidant activity of plasma as a consequence of an
      inflammatory reaction induced by subcutaneous turpentine in the rabbit.
AB  - In the rabbit, an acute inflammatory reaction triggered by the subcutaneous
      administration of turpentine induces in hepatic tissues an oxidative stress, as
      well as a decrease in activity of enzymatic scavengers of reactive oxygen species
      (ROS). The objective of this study was to investigate, the repercussions of a
      local inflammatory reaction on the antioxidant capacity and markers of systemic
      oxidative stress in plasma. To this purpose, rabbits received a.s.c. injection of
      turpentine (5 mL/kg) or NaCl 0.9% (w/v). Blood samples were collected at
      different times during the 48 hours of the experiment to evaluate: firstly, the
      antilipoperoxidant activity of plasma by measuring the inhibition of autoxidation
      of brain homogenate, and the concentrations of tocopherol and ascorbic acid;
      secondly, the severity of oxidative stress in plasma by assaying the
      concentration of thiobarbituric acid reactive substances (TBARS), and the
      concentration of ascorbyl radical. The results show that the antilipoperoxidant
      capacity of plasma gradually increased to be 167% higher than baseline values (p
      < 0.05) after 48 hours of experiment. alpha-Tocopherol and ascorbic acid levels
      increased by 49% and 80%, respectively (p < 0.05) during the first 24 hours.
      Lipid peroxidation continuously increased to be 98% higher than baseline values
      (p < 0.05) at 48 hours, while ascorbyl radical levels were not modified (p <
      0.05). In summary, an acute local inflammatory reaction causes a steady
      progression of oxidative stress, while it stimulates the antilipoperoxidant
      activity of plasma, to which alpha-tocopherol and ascorbic acid appear to
      contribute, essentially early in the inflammation.

PMID- 7581820
TI  - Free radical DNA adduct 8-OH-deoxyguanosine affects activity of Hpa II and Msp I
      restriction endonucleases.
AB  - 8-OH-deoxyguanosine can diminish the ability of the restriction endonucleases Hpa
      II and Msp I to cleave DNA. The exact position of the adduct within the
      recognition site appears to determine the extent of the effect.

PMID- 7581821
TI  - The inhibition of foam cell formation by sodium diethyldithiocarbamate.
AB  - A prominent feature of human atherosclerosis is the lipid-laden foamy macrophage,
      which often also contains the insoluble pigment, ceroid. The culture of
      macrophage-like cells, P388D1s, with artificial lipoproteins composed of
      cholesteryl linoleate (CL) and bovine serum albumin (BSA) results in foam cell
      formation with lipoprotein uptake and the intracellular accumulation of ceroid.
      Ceroid accumulation is accompanied by the oxidation of the cholesterol ester as
      monitored by gas chromatography. The sodium salt of diethyldithiocarbamic acid
      (DDC) at 1-5 microM effectively inhibited lipoprotein uptake, cholesteryl
      linoleate oxidation and ceroid accumulation in cultures of P388D1. Further
      studies showed that intracellular ceroid accumulation appeared to require the
      presence of cystine in the medium. Lipoprotein oxidation by this macrophage-like
      cell therefore appears to involve a mechanism dependent on cystine metabolism
      which is consistent with previous reports of macrophage-mediated lipoprotein
      oxidation. Studies on CL/BSA-induced ceroid accumulation in human monocytes also
      showed that DDC behaved in much the same manner. This inhibitory effect of DDC on
      foam cell formation, often considered a primary event of atherosclerosis, at
      concentrations as low as 1 microM, suggests the need for further, more
      comprehensive, studies on this compound's activities.

PMID- 7581823
TI  - Spin trapping isotopically-labelled nitric oxide produced from [15N]L-arginine
      and [17O]dioxygen by activated macrophages using a water soluble Fe(++)
      dithiocarbamate spin trap.
AB  - The unique capabilities of EPR spin trapping of nitric oxide based on a ferrous
      dithiocarbamate spin trap have been demonstrated in a study verifying the source
      of the nitrogen and oxygen atoms in nitric oxide produced from activated
      macrophages. Spin trapping experiments were performed during nitric oxide
      generation from activated mouse peritoneal macrophages using the ferrous complex
      of N-methyl D-glucamine dithiocarbamate as a spin trap. When 15N-substituted
      arginine was given to the activated macrophages in the presence of the spin trap,
      a characteristic EPR spectrum of the nitric oxide spin adduct was obtained, which
      indicates the presence of the 15N atom in the nitric oxide molecule. The
      hyperfine splitting (hfs) constant of the 15N nucleus was 17.6 gauss. When 17O
      containing dioxygen (55%) was supplied to the medium, an EPR spectrum consistent
      with the 17O-substituted nitric oxide spin adduct was observed in the composite
      spectrum. The hfs of 17O was estimated to be 2.5 gauss. The 14NO spin adduct
      observed after prolonged incubation in the medium which contains [15N]L-arginine
      as the only extracellular source of arginine demonstrates that arginine is
      recycled through its metabolite in activated macrophages.

PMID- 7581822
TI  - The influence of fatty acid micelles on the assays for SOD activity.
AB  - The influence of fatty acid (FA) micelles on cytochrome c(cyt.c) reduction and
      nitroblue tetrazolium (NBT) reduction assays for SOD activity, which continue to
      be widely used, has been studied. In the presence of FA micelles, the use of
      cyt.c reduction assay was found to overestimate the real activity of SOD. This
      effect is attributed to the following reasons. 1. The FA micelles lead to the
      denaturation of cyt.c, which gives rise to suppression of the reactivity of
      ferricyt.c(cyt.c(ox)) towards O2-. Furthermore, this denaturation increases the
      reoxidation rate of ferrocyt.c, and consequently the reoxidation causes a
      decreased rate of cyt.c(ox) reduction. 2. Positively charged cyt.c(ox) interacts
      with negatively charged FA micelles, and so cyt.c(ox) on the surface of FA
      micelles reacts less with negatively charged O2- because of electrostatic
      repulsion. Also in NBT reduction assay using a positively charged probe molecule,
      FA micelles cause the appearance of enhancement of SOD activity, due to
      suppression of the reactivity of NBT towards O2- by electrostatic repulsion.
      However, in both chemiluminescence assay using the uncharged probe molecule and
      LDH-NADH assay using the negatively charged probe molecule, FA micelles cannot
      influence the assays of the SOD activity, because the micelles do not interact
      electrostatically with probe molecules.

PMID- 7581824
TI  - Enhancement of lipid peroxidation by indole-3-acetic acid and derivatives:
      substituent effects.
AB  - The peroxidation of liposomes by a haem peroxidase and hydrogen peroxide in the
      presence of indole-3-acetic acid and derivatives was investigated. It was found
      that these compounds can accelerate the lipid peroxidation up to 65 fold and this
      is attributed to the formation of peroxyl radicals that may react with the
      lipids, possibly by hydrogen abstraction. The peroxyl radicals are formed by
      peroxidase-catalyzed oxidation of the enhancers to radical cations which undergo
      cleavage of the carbon-carbon bond on the side-chain to yield CO2 and carbon
      centred radicals that rapidly add oxygen. In competition with decarboxylation,
      the radical cations deprotonate reversibly from the N1 position. Rates of
      decarboxylation, pka values and rate of reaction with the peroxidase compound I
      indicate consistent substituent effects which, however, can not be quantitatively
      related to the usual Hammett or Brown parameters. Assuming that the rate of
      decarboxylation of the radical cations taken is a measure of the electron density
      of the molecule (or radical), it is found that the efficiency of these compounds
      as enhancers of lipid peroxidation increases with increasing electron density,
      suggesting that, at least in the model system, the oxidation of the substrates is
      the limiting step in causing lipid peroxidation.

PMID- 7581826
TI  - Reaction of bromotrichloromethane derived free radicals with uracil in a model
      system. Structures of products formed.
AB  - Free radicals generated by benzoyl peroxide-mediated catalytic decomposition of
      bromotrichloromethane (eg. trichloromethyl) were allowed to react under nitrogen
      or under air with uracil. Under nitrogen two reaction products were formed, one
      was identified as 5-chlorouracil and the other as a 5-bromouracil. Under air,
      besides the above two products other nine were also formed: 5,6-dihydrouracil; 5
      hydroxyuracil; a chlorohydroxy adduct of uracil; a bromohydroxy derivative of
      uracil having the 5,6 bond in the saturated form; other bromohydroxy derivative
      of uracil having the double bond intact; 5,6-dihydroxyuracil; two dihalogenated
      hydroxylated uracil derivatives and one peak we were not able to descipher its
      structure. No single reaction product formed had carbon centered radicals (eg.
      trichloromethyl) added from CBrCl3 and consequently would be missed in 'in vivo'
      covalent binding studies where 14C haloalkane (CBrCl3 or carbon tetrachloride)
      were employed. If similar reaction products resulted during interaction of CBrCl3
      reactive metabolites with uracil in RNAs, significant deleterious effects in
      their function would be expected. That possibility, however, remains to be
      established.

PMID- 7581827
TI  - A new nitric oxide (NO) releaser: spontaneous NO release from FK409.
AB  - The remarkable vasorelaxant and anti-platelet effects of FK409 have been reported
      to be due to nitric oxide (NO) release. The purpose of the present study is to
      investigate the spontaneous NO-releasing pathway of FK409 in aqueous solutions.
      1H-NMR spectra of FK409 suggested that the compound underwent a time-dependent
      elimination of the hydrogen atom at alpha-position of the nitro moiety (at the 5
      position) in weakly alkaline solutions. In addition, the degradation of FK409
      monitored by HPLC showed a pH-dependency accelerating with an increase of pH.
      These results revealed that the first step in the degradation of FK409 might be
      the hydroxyl ion-dependent subtraction of the hydrogen atom at the 5-position. On
      the other hand, NO release from FK409 also exhibited a pH-dependency, and the
      velocity of NO liberation was markedly enhanced above pH 6. Furthermore, a linear
      relationship between the rate of FK409 degradation and that of NO formation was
      observed, indicating that the rate-limiting step for NO formation is the same as
      that for degradation. Thus, the rate-limiting process of NO formation from FK409
      is due to the deprotonation reaction of the hydrogen atom at the 5-position by
      hydroxyl ions. The deprotonation process appears to be an essential step for both
      FK409 degradation and NO release. On the basis of the results, a possible kinetic
      scheme for NO release from FK409 is proposed.

PMID- 7581825
TI  - Antioxidative activity of 5,6,7,8-tetrahydrobiopterin and its inhibitory effect
      on paraquat-induced cell toxicity in cultured rat hepatocytes.
AB  - The in vitro antioxidative activity of 5,6,7,8-tetrahydrobiopterin (BPH4) was
      measured and the ability of BPH4 to prevent paraquat-induced cell damage was
      examined in cultured hepatocytes. The scavenging activity of BPH4 against
      superoxide anion radicals was assayed in two systems, i.e., xanthine/xanthine
      oxidase (X/XOD) and rat macrophage/phorbol myristate acetate (M psi/PMA) radical
      generating systems. BPH4 showed an extremely strong superoxide anion radical
      scavenging activity in both assay systems. Biopterin (BP) itself did not show any
      activity in the X/XOD system, but was effective in the M psi/PMA system. The
      antioxidative activities of BPH4 against both superoxide anion and hydroxyl
      radicals were confirmed by spin trapping-ESR spectrometry. BPH4 also protected
      rat brain homogenate against auto-oxidation. We further examined the effect of
      BPH4 on paraquat-induced cell toxicity in cultured rat hepatocytes. The paraquat
      induced elevation of the release of lactate dehydrogenase (LDH), a marker enzyme
      for cytotoxicity from cultured hepatocytes was suppressed by BPH4 in a dose
      dependent manner. The elevation of lipid peroxides simultaneously induced by
      paraquat was also inhibited by BPH4 in the same manner. These results suggest
      that BPH4 might be useful in the treatment of various diseases whose pathogenesis
      is active oxygen-related.

PMID- 7581828
TI  - Reactions of low valent transition metal complexes with hydrogen peroxide. Are
      they "Fenton-like" or not? 4. The case of Fe(II)L, L = edta; hedta and tcma.
AB  - The question whether hydroxyl free radicals are formed in the reactions of
      divalent iron complexes Fe(II)L; L = edta; hedta; tcma (tcma = 1-acetato-1,4,7
      triazacyclononane) with hydrogen peroxide in neutral and slightly acidic
      solutions was studied by using the beta elimination reaction as an assay for the
      formation of hydroxyl free radicals, OH. The results show that at pH < 5.5 the
      iron(II)peroxide intermediate complex decomposes rapidly to yield free hydroxyl
      radicals for L = edta and hedta. This is in contrast to the mechanism of the
      corresponding Fe(II)nta peroxide complex, which probably decomposes to form
      Fe(IV)nta which then reacts with organic substrates to yield aliphatic free
      radicals. Thus, the non-participating ligand L has an appreciable effect on the
      mechanism of reaction of the metal center with hydrogen peroxide. Blank
      experiments using ionizing radiation as the source of .CH2CR(CH3)OH, R = H or CH3
      radicals indicate that when L = tcma intermediates of the type LFeIII
      CH2CR(CH3)OHaq are formed, but their major mode of decomposition is not the beta
      elimination reaction. Thus, the present assay for the formation of hydroxyl free
      radicals by the Fenton Reaction does not fit the latter system.

PMID- 7581829
TI  - Metal ion release from mechanically-disrupted human arterial wall. Implications
      for the development of atherosclerosis.
AB  - Oxidation of low density lipoproteins (LDL) in blood vessel walls plays a
      significant role in the development of atherosclerosis. LDL oxidation in vitro is
      greatly accelerated by the presence of "catalytic" iron or copper ions, which
      have already been shown to be present within advanced atherosclerotic lesions. We
      demonstrate here that mechanical damage to human arterial wall samples (both
      normal and early or intermediate atherosclerotic lesions) causes release of
      "catalytic" iron and copper ions, to an extent increasing with the damage. It may
      be that traumatic (e.g. during angioplasty) or other injury to the vessel wall
      contributes to the generation of metal ions that can facilitate LDL oxidation and
      other free radical reactions, so promoting atherosclerosis.

PMID- 7581830
TI  - Hydrogen peroxide and the proliferation of BHK-21 cells.
AB  - Intracellular levels of H2O2 in BHK-21 cells are not static but decline
      progressively with cell growth. Exposure of cells to inhibitors of catalase, or
      glutathione peroxidase, not only diminishes this decline but also depresses rates
      of cell proliferation, suggesting important growth regulatory roles for those
      antioxidant enzymes. Other agents which also diminish the growth-associated
      decline in intracellular levels of H2O2, such as the superoxide dismutase mimic,
      copper II-(3,5-diisopropylsalicylate)2, or docosahexaenoic acid, also reduced
      cell proliferation. In contrast, proliferation can be stimulated by the addition
      of 1 microM exogenous H2O2 to the culture medium. Under these conditions,
      however, intracellular levels of H2O2 are unaffected, whereas there is a
      reduction in intracellular levels of glutathione. It is argued that critical
      balances between intracellular levels of both H2O2 and glutathione are of
      significance in relation both to growth stimulation and inhibition. In addition
      growth stimulatory concentrations of H2O2, whilst initially leading to increased
      intracellular levels of lipid peroxidation breakdown products, appear to
      "trigger" their metabolism, possibly through aldehyde dehydrogenase, whose
      activity is also stimulated by H2O2.

PMID- 7581831
TI  - Levels of antioxidant nutrients in plasma and low density lipoproteins: a human
      volunteer supplementation study.
AB  - A human supplementation study was undertaken in order to investigate the
      correlation between the intake of individual daily dosages of vitamin E (300 mg),
      vitamin C (250 mg), or beta-carotene (15 mg) of eight week duration and their
      uptake in vivo in plasma and LDL. The effects of a combined supplement of vitamin
      E, vitamin C and beta-carotene (Redoxon protector-75 mg, 150 mg, 15 mg
      respectively) were also investigated. The results show that on supplementation
      with the individual antioxidants the increases in plasma alpha
      tocopherol:cholesterol levels lie in the 1.5-2 fold range and the beta
      carotene:cholesterol ratios give a mean 3.5 fold enhancement. The combined
      supplement containing the same level of beta-carotene as the single dosage
      achieved comparative levels of uptake in plasma. The level of plasma vitamin C
      appears to be maximal at about 100 microM regardless of the pre-supplementation
      level.

PMID- 7581832
TI  - Evaluation of the immunogenicity of polymerized hemoglobin solutions in a rabbit
      model.
AB  - Chemical modification of proteins carries the risk that neo-antigens are
      introduced. To investigate the potential immunogenicity of human glutaraldehyde
      polymerized hemoglobin (polyHbX1), we analyzed the antibody responses of rabbits
      after hyperimmunization with complete Freund's adjuvant. In view of the species
      difference, we also tested rabbit hemoglobin that was modified in the same way as
      human polyHbX1. Thereafter, we studied the antibody response after weekly
      intravenous infusion of clinically relevant doses of polyHbX1 to evaluate whether
      an immune response is likely to occur when modified hemoglobin is used as blood
      substitute. The occurrence of an antibody response was tested by using an enzyme
      immunoassay (ELISA). To find out whether antibodies were directed against neo
      epitopes on human polyHbX1 we used a competitive ELISA. The results showed that
      polymerized hemoglobin may weakly activate the immune system in special
      conditions, but is unlikely to do so when it is used as blood substitute.

PMID- 7581833
TI  - Protective effect of selenium on hemoglobin mediated lipid peroxidation in vivo.
AB  - The toxicity of hemoglobin (Hb) solutions is related, at least in part, to the
      generation of oxygen free radicals with consequent induction of lipid
      peroxidation. The present study was designed to examine whether selenium (Se) may
      prevent the oxidative damage observed after Hb administration. Three groups of
      rats were compared; (I) the negative control group receiving autotransfusion;
      (II) the positive control group with replacement of 40% total blood volume (TBV)
      with modified bovine Hb solution; and (III) the experimental group which received
      dietary supplemented selenium (Na2SeO3) in daily doses of 5 micrograms.kg body wt
      1 in drinking water, 4 days before and 3 days after administration of Hb solution
      in the same volume as in group II. Three days after Hb injection, all animals
      were sacrificed. Oxidative stress was determined by measuring conjugated dienes
      (CD) and thiobarbituric acid reactants (MDA) in homogenates of the perfused
      liver, heart, lungs, kidney, brain and plasma. Additionally, the 45k x g
      supernatants of the organs homogenates and plasma were assayed for the
      antioxidant enzymes activity: superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GSH-Px) and the intracellular level of reduced
      glutathione (GSH). Also, a measurement of nonprotein bound intracellular free
      iron (Fe) and tissue Se concentrations was performed. Simultaneously, injury
      dysfunction of vital organs was assessed by the measurement of plasma LDH, SGPT,
      creatinine, blood PaO2 and by histopathological studies. Results indicate that
      the exchange transfusion with Hb solution introduced significant increases in CD
      and MDA formation, particularly in the liver and heart tissues, and in plasma.
      While the values of the SOD and CAT in the liver and heart tissue were generally
      altered, the SOD/CAT ratio was also increased. After the Hb injection, activity
      of GSH-Px remained unchanged and was associated with significant depletion of
      GSH. The plasma levels of SGPT and LDH were increased, but the creatinine and
      PaO2 was similar to that of the control and corresponded with histopathological
      findings. The liver and heart intracellular free Fe was found to be higher than
      that of control. Treatment with Se was very effective in the prevention of
      oxidative damage introduced by Hb. Full protection from MDA formation was noted
      in liver tissue (p < 0.001). Also, plasma levels of MDA, SGPT and LDH were
      significantly decreased and appeared similar to that of the control group (I).
      Treatment with Se increased liver (p < 0.05) and plasma (p < 0.1) level of GSH
      Px.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7581834
TI  - Effects of halogenated and non-halogenated anesthetics on diaspirin cross-linked
      hemoglobin induced contractions of porcine pulmonary veins.
AB  - Diaspirin crosslinked hemoglobin (DCLHb) is a resuscitative fluid presently
      undergoing clinical trials. Administration of DCLHb is associated with an
      elevation of mean arterial pressure in vivo and contraction of isolated blood
      vessels in vitro. The mechanisms for the vascular actions are unknown but may be
      due to inhibition of nitric oxide (NO). Halothane has been reported to inhibit NO
      induced relaxation. We examined the effect of anesthetics on DCLHb induced
      contraction of blood vessels. Porcine pulmonary veins were excised, cut into
      rings and placed in organ chambers filled with 25 ml Krebs-Ringer solution (37
      degrees C). Following equilibration at their optimal length the rings were
      exposed to increasing concentrations of serotonin(10(-8)M-10(-5)M). Endothelial
      activity was confirmed by relaxation greater than 80% with ACh (10(-6)M). DCLHb
      (1.5 x 10(-8)M to 6 x 10(-7)M) contracted porcine pulmonary veins (1.04 +/- 0.17g
      to 3.45 +/- 0.22g), and halothane (0.5% and 1%) significantly inhibited these
      DCLHb induced contractions in a dose-related manner (-41.6 +/- 8.1% and -73.3 +/-
      8.2%, respectively). At equi-molar concentrations, isoflurane had no inhibitory
      activity. The relative effect of these volatile anesthetics is consistent with
      their inhibitory actions on other heme containing proteins. Propofol (10(-5)M)
      only has inhibitory effects on lower concentrations of DCLHb. Fentanyl did not
      have inhibitory effects. These results suggest that halogenated anesthetics may
      interact with the heme iron of DCLHb and inhibit its binding with NO.

PMID- 7581837
TI  - Effects of a 100% perfluorooctylbromide emulsion on ischemia/reperfusion injury
      following cardioplegia.
AB  - Protective effects of a perfluorooctylbromide emulsion on myocardial ischemia and
      reperfusion (MI/R) injury were evaluated in a modified Langendorff rat heart
      preparation. Isolated rat hearts were equilibrated in Krebs-Henseleit solution
      (KH) for 35 minutes and perfused with either cardioplegic solution (CPS) or a
      100% perfluorooctylbromide (PFOB) emulsion in CPS for 3 minutes. Hearts were then
      bathed in the emulsion or CPS. Both groups were subjected to 30 minutes of
      ischemia. Following 30 minutes of ischemia and 30 minutes of reperfusion with KH
      solution, hearts subjected to the 100% PFOB emulsion showed improved recovery of
      left ventricular function. Tissue activities of the antioxidant enzymes
      glutathione peroxidase, superoxide dismutase, and catalase were not affected by
      the emulsion in this model. Activity of lactate dehydrogenase (LDH) in the
      bathing medium was elevated at the end of the experimental period in both control
      and PFOB-treated hearts. The PFOB emulsion reduced the decline in ATP and GSH
      levels produced by cardioplegia and subsequent reperfusion. No differences were
      noted in oxidized glutathione (GSSG) levels. These data suggest that the PFOB
      emulsion provides some protection for the myocardium against injury associated
      with cardioplegia.

PMID- 7581839
TI  - Preparation and characterization of chitosan-entrapped microsomal UDP-glucuronyl
      transferase.
AB  - The hepatic microsomal UDP-Glucuronyl transferase which catalyze the
      glucuronidation of drugs, pesticides, carcinogens and other xenobiotics, was
      immobilized by entrappment in chitosan. Chemical and physical characterization
      were made by using 1-naphthol as substrate. Thermal, storage and operational
      stabilities of the immobilized enzyme was also searched and found to be better in
      comparison with the free enzyme. In conclusion, chitosan gel beads appear to have
      good characteristics for use as UDPGT immobilization support suitable for large
      scale use and offer the prospect that immobilized UDPGT may become an important
      form of catalyst in medicine.

PMID- 7581838
TI  - Substrate specificity and the use of chitosan-entrapped rabbit hepatic microsomal
      UDP-glucuronyl transferase for detoxification.
AB  - Rabbit hepatic microsomal UDP-Glucuronyl transferase (EC.2.4.1.17) was
      immobilized in chitosan, which is an ionotropic gelatation agent, and the
      resulting preparation was used as a biocatalyst for the glucuronidation of toxic
      substances and drugs such as; 1-naphthol, phenol, 4-nitrophenol, bilirubin,
      testesterone, estrone, lamotrigine, imipramine and chlorpromazine. For studying
      the drug metabolism in vitro and obtaining artificial liver support
      (detoxification) chitosan-entrapped UDPGT towards 1-naphthol was tested by using
      two model reactor system. The conversion curves of 1-naphthol to its glucuronide
      indicated that the column reactor system was found to be better and seems
      suitable for detoxification with a high yield of glucuronide formation.

PMID- 7581836
TI  - Mechanistic study on toxicity of positively charged liposomes containing
      stearylamine to blood.
AB  - We studied the interaction of stearylamine (SA) containing liposomes (SA
      liposomes) with erythrocyte ghost (EG) or platelets, utilizing the
      Tb/dipicolinate (Tb/DPA) assay for the mixing of aqueous contents and a resonance
      energy transfer (RET) assay for the mixing of lipid. The results demonstrate that
      SA-liposomes and EG, after aggregation, have a great tendency to mix their lipid
      before the mixing of the internal contents. The mixing of their contents takes
      place inside the vesicles due to the fusion of SA-liposomes and EG, followed by
      the leakage of the contents from the vesicles. In the presence of carboxymethyl
      chitin (CM-chitin), SA-liposomes-EG interaction was inhibited, indicating that CM
      chitin reduces the tendency of SA-liposomes to interact with EG. The lipid mixing
      between SA-liposomes and platelets was not affected by CM-chitin or phagocytosis
      inhibitors: EDTA, cytochalasin B, or 2,4-dinitrophenol and iodoacetate,
      indicating the importance of glycoproteins on the platelet membrane surface in
      the interaction of SA-liposomes with platelets.

PMID- 7581835
TI  - Assessment of dextran 10-benzene-tetracarboxylate-hemoglobin, an oxygen carrier,
      using guinea pig isolated bowel model.
AB  - With the aim of assessing of dextran-benzene-tetracarboxylate hemoglobin as an
      oxygen carrier, we studied histological changes in the intestinal loop in
      anesthetized guinea pig. The intestinal tissue being very sensitive to hypoxia,
      an innervated loop was vascularly perfused with open-flow during one hour at zero
      hematocrit. To estimate the capacity of hemoglobin solution to oxygenate this
      tissue, we observed the mechanical and histological changes in the organ and the
      arterio-venous difference in PO2, oxyhemoglobin, deoxyhemoglobin and we compared
      them with human albumin, Tyrode and non-modified hemoglobin. The PO2
      arteriovenous differences were 51.9 +/- 7.1 torr (m +/- SEM) for Tyrode, 40.2 +/-
      6.4 torr for albumin solution, 113.7 +/- 6.5 torr for non-modified hemoglobin and
      132.7 +/- 6.8 torr for dex-BTC-Hb. Compared to albumin and Tyrode solutions,
      hemoglobin solutions transferred more oxygen to tissues. The desaturation of dex
      BTC-Hb was significantly superior (p < 0.05) to the one non-modified hemoglobin.
      With Hb solutions, this desaturation increased with time and it depended on the
      perfusion flow. The structure of jejunal villi when perfused with a hemoglobin
      solution, remained almost normal and the loop was still active. Nevertheless, non
      modified hemoglobin leaked from the vessels to the lumen and caused edema and a
      rupture of overlapping epithelium at the tip of the villi. With dex-BTC-Hb, such
      histological modifications were less significant. With albumin and Tyrode, all
      villi were totally necrosed and the loop was completely inert. We have
      demonstrated that dextran-benzene-tetracarboxylate hemoglobin had the ability to
      maintain the tissue alive thanks to its good capacity to release oxygen and its
      satisfactory vascular persistence. Dex-BTC-Hb solution can answer to needs of
      tissue.

PMID- 7581841
TI  - Hemoglobin analysis by capillary zone electrophoresis.
AB  - The analysis of haemoglobin is routine in medical laboratories for the purpose of
      assessing blood disorders and related pathologies. Haemoglobin is structurally
      diverse and possesses many variant forms, some disease-producing. With recent
      improvements in technology, capillary electrophoresis is now being adapted in the
      clinical laboratory. This paper describes the analysis of haemoglobin variants
      using uncoated fused-silica capillaries. The effects of using different buffer
      salts at different concentrations with different buffer pH values to separate
      haemoglobin variants in these capillaries are described.

PMID- 7581840
TI  - Capillary electrophoresis of hair proteins modified by alcohol intake in
      laboratory rats.
AB  - A capillary zone electrophoretic method was used to obtain profiles of
      solubilized rat hair keratin proteins. The same methodology was used to reveal
      the presence of additional protein peaks in alcohol-consuming rats. Two types of
      separation were investigated. Alkali-solubilized keratins from hair of rats
      treated for 5 weeks with 5% ethanol and 2 weeks with 10% ethanol (instead of
      drinking water) and from controls were analysed. Whereas under alkaline
      conditions (pH 9.2, 50 mM borate) an additional fraction of "low-sulphur"
      keratins with the highest anodic mobility of this keratin category was shown in
      alcohol-treated animals, acid electrophoresis carried out at pH 3.5 in phosphate
      buffer (50 mM) revealed the presence of two sharp peaks absent in the controls.
      These findings were confirmed by two-dimensional separations of carboxymethylated
      keratin samples. An attempt was made to identify further one of the newly
      occurring fractions in alcohol-consuming animals. It was revealed that the
      tryptic hydrolysate of "low-sulphur" proteins obtained from alcohol-consuming
      animals contained a peptide not found in controls.

PMID- 7581845
TI  - High-performance liquid chromatographic and capillary electrophoretic
      determination of free nicotinic acid in human plasma and separation of its
      metabolites by capillary electrophoresis.
AB  - Two methods are described based on high-performance liquid chromatography and
      capillary electrophoresis that provide the selective and sensitive determination
      of nicotinic acid in human plasma. Moreover, the capillary electrophoresis system
      was used for the separation of nicotinic acid, nicotinamide, nicotinamide N
      oxide, N'-methylnicotinamide, 6-hydroxynicontinic acid, nicotinuric acid and
      barbital (internal standard). The extraction procedure is simple; no gradient
      elution or derivatization is required. Both methods can be useful for clinical
      and biomedical investigations.

PMID- 7581844
TI  - Stability measurements of antisense oligonucleotides by capillary gel
      electrophoresis.
AB  - The approach of using antisense oligonucleotides as potential drugs is based on
      hybridization of a short chemically-modified oligonucleotide with complementary
      cellular DNA or RNA sequences. A critical question is the stability of chemically
      modified antisense oligonucleotides in cellular environments. In a model system,
      resistance against various nucleases was evaluated by capillary gel
      electrophoresis (CGE). For some of the samples, matrix assisted laser desorption
      and ionization mass spectrometry (MALDI-MS) was used as an additional analytical
      tool to perform stability measurements. Using CGE, the enzymatic degradation of
      single nucleotides from the oligomer can be followed after different incubation
      times. 10% T polyacrylamide gels give baseline resolution for oligonucleotides
      ranging between 5 and 30 bases in length. The kinetic influence of a specific
      nuclease concentration and the antisense oligonucleotide structure on the
      cleavage reaction are discussed. Also, a simple desalting method to improve the
      injection efficiency and sensitivity of the method are described. Examples of
      measurements of chemically modified antisense 19-mers are presented.

PMID- 7581842
TI  - Detection of traces of a trisulphide derivative in the preparation of a
      recombinant truncated interleukin-6 mutein.
AB  - A new mutein of interleukin-6, called delta 22-IL-6 Cys 3,4, characterized by the
      deletion of the first 22 amino acids at the N-terminal end and by the
      substitution of the first two cysteines (Cys23 and Cys29) with serine residues,
      was produced in Escherichia coli and was found to maintain the structural and
      functional properties of the human native form. A partially purified preparation
      still showed in isoelectric focusing a minor acidic component (pI 6.10) and a
      more basic component (pI 6.70), the native form having a pI of 6.56. This
      preparation was further fractionated in a multi-compartment electrolyser with
      isoelectric membranes, which allowed the collection of the more alkaline species
      for characterization. Mass spectra of the pI 6.70 form gave an additional mass of
      32 atomic mass units (amu), suggesting the addition of two oxygen atoms (a
      potential oxidation of two methionine residues to sulphoxide). However, the five
      methionine residues in this higher pI form were identified after enzymatic
      hydrolysis and peptide mapping and were found to be in a reduced state. In
      addition, the pI 6.70 form was quickly converted into the native form by mild
      reductive treatment. On digestion and fingerprinting, the peptide from residues
      50 to 65 of the pI 6.70 species (containing the only two cysteine residues of the
      molecule) exhibited a more hydrophobic behaviour in reversed-phase high
      performance liquid chromatography and retained a mass increase of 32 amu. These
      experimental findings more likely suggest the addition of an extra sulphur atom
      to the only disulphide bridge to give an unusual protein trisulphide molecule.

PMID- 7581843
TI  - Modification of a tunable UV-visible capillary electrophoresis detector for
      simultaneous absorbance and fluorescence detection: profiling of body fluids for
      drugs and endogenous compounds.
AB  - Using fused-silica optical fibres for fluorescence light collection and bandpass
      filters for selection of emission wavelengths, a capillary electrophoresis
      detection cell of a conventional, tunable UV-Vis absorbance detector was adapted
      for simultaneous fluorescence (at selected emission wavelength) and absorbance
      (at selected excitation wavelength) detection. Detector performance is
      demonstrated with the monitoring of underivatized fluorescent compounds in body
      fluids by micellar electrokinetic capillary chromatography with direct sample
      injection. Compared with UV absorption detection, fluorescence detection is shown
      to provide increased selectivity and for selected compounds also up to tenfold
      higher sensitivity. Examples studied include screening for urinary indole
      derivatives (tryptophan, 5-hydroxytryptophan, tyrosine, 3-indoxyl sulfate and 5
      hydroxyindole-3-acetic acid) and catecholamine metabolites (homovanillic acid and
      vanillylmandelic acid) and the monitoring of naproxen in serum, quinidine in
      serum and urine and of salicylate and its metabolites in serum and urine.

PMID- 7581846
TI  - Capillary electrophoresis device with double UV detection and its application to
      the determination of effective mobilities of peptides.
AB  - A new experimental device for high-performance capillary electrophoresis (HPCE)
      with a double UV detection system and with thermostating of the whole separation
      compartment was developed. UV detection is doubled by producing two apertures
      placed symmetrically close to the axis of the optical path of the single-beam UV
      detector and by the adjustment of the capillary loop on these two apertures. The
      double-detection system allows exact measurements of electrophoretic and
      electroosmotic flow velocities. A procedure for the determination of effective
      mobilities from the data obtained by the double UV detection system was developed
      and applied to determine the effective mobilities of synthetic peptides
      (diglycine, triglycine, growth hormone releasing peptide and its derivatives and
      fragments). The measurements are performed at constant temperature (25 degrees C)
      and low input power at which temperature increase in the capillary can be
      neglected and temperature corrections of temperature-dependent magnitudes need
      not be included in the calculations.

PMID- 7581847
TI  - Capillary zone electrophoresis of serum proteins: study of separation variables.
AB  - Electrophoresis of serum proteins is one of the traditional applications of zone
      electrophoresis. Whereas electrophoresis in supporting media uses usually 5,5'
      diethylbarbiturate at pH 8.6 as the buffer, in capillary zone electrophoresis
      with on-line UV detection, this electrolyte is of little use because of its high
      UV absorbance. For that reason, a number of operational electrolytes differing in
      composition were tested for use in capillary electrophoresis of serum proteins.
      The influence of the pK(A) of co-ions and counter ions and the concentration of
      the operational electrolyte was examined. If 0.1 M methylglucamine-0.1 M epsilon
      aminocaproic acid or 0.1 M methylglucamine, -0.1 M gamma-aminobutyric acid is
      used as the operational electrolyte, capillary electrophoresis separates serum
      proteins into more than ten zones.

PMID- 7581848
TI  - Lipopolysaccharide determination by reversed-phase high-performance liquid
      chromatography after fluorescence labeling.
AB  - A sensitive method for the quantitative determination of lipid A, the covalently
      bound hydrophobic component of lipopolysaccharides (endotoxins), has been
      developed. The determination of lipid A was based on the quantitative measurement
      of beta-hydroxymyristic acid and beta-hydroxylauric acid by reversed-phase HPLC.
      beta-Hydroxy acids were liberated from ester and amide linkages in endotoxins by
      acid catalyzed methanolysis. The resulting methyl esters were derivatized with 9
      anthracene-carboxyl chloride, 9-fluorene-carboxyl chloride and 4-(1
      pyrenyl)butyric acid chloride and quantified with a fluorescence detector. The
      effectiveness of the three derivatizing agents was compared. As internal
      standards-beta-hydroxytridecanoic acid [beta-OH(13:0)] and beta
      hydroxypentadecanoic acid [beta-OH(15:0)] ethyl esters were used. The limits of
      detection of beta-hydroxymyristic acid were 0.5 pg for the 9-anthroyl and 2 pg
      for the fluorenoyl and 4-(1-pyrenyl)butyroyl ester per sample (signal-to-noise
      ratio of 3). The detection limits of lipopolysaccharide from a smooth strain
      (Escherichia coli 0111:B4) was 20 pg, while that from two rough strains (E. coli
      Nissle 1917 and Salmonella typhimurium SL 1181) was 5 pg per sample after
      methanolysis and derivatization with 9-anthroyl chloride.

PMID- 7581849
TI  - Combined polymerized chiral micelle and gamma-cyclodextrin for chiral separation
      in capillary electrophoresis.
AB  - A combination of a polymerized chiral micelle, poly(sodium N-undecylenyl-D
      valinate) [poly(D-SUV)] and gamma-cyclodextrin (gamma-CD) is used for the first
      time for chiral separation in capillary electrophoresis. A simple theory is
      presented to rationalize the synergistic effect of the enantioselectivity
      obtained by use of poly(D-SUV) and gamma-CD in combination. A mixture of four
      enantiomeric pairs is successfully resolved by use of this combination. The
      resolutions of the enantiomers using this approach are far superior to those
      obtained by use of either poly(D-SUV) or gamma-CD alone. In addition, the effects
      of the antipode (L-SUV), gamma-CD concentration, buffer concentration, organic
      solvents, and urea concentration on the resolution are also examined.

PMID- 7581850
TI  - Gel electrophoretic analysis of cellular and secreted proteins from resting and
      activated rat alveolar macrophages treated with pentamidine isethionate.
AB  - Pneumocystic carinii pneumonia, which is a major cause of death among patients
      suffering from acquired immunodeficiency syndrome, has often been treated
      successfully with pentamidine isethionate. This study examines pentamidine
      effects on cellular and secreted proteins from rat alveolar macrophages by two
      dimensional gel electrophoresis and computerized image analysis. Over 100
      secreted proteins were detected by fluorography. Fluorography showed pentamidine
      diminished tumor necrosis factor and interleukin-1 release along with other
      proteins. Effects of combined bacterial lipopolysaccharide and pentamidine were
      more pronounced on secreted versus cellular proteins in protein amount and
      pattern difference. Thus pentamidine exhibited a general repressive effect on
      cellular and secreted protein expression in resting and activated macrophages.

PMID- 7581851
TI  - Chromium speciation by anion-exchange high-performance liquid chromatography with
      both inductively coupled plasma atomic emission spectroscopic and inductively
      coupled plasma mass spectrometric detection.
AB  - Development of a new method for the determination of Cr(III) and Cr(VI) is
      described. Anion-exchange high-performance liquid chromatography (HPLC) was used
      to separate Cr(III) and Cr(VI) with on-line detection by inductively coupled
      plasma atomic emission spectroscopy (ICP-AES) at 2766 A in preliminary studies,
      and inductively coupled plasma mass spectrometry (ICP-MS) with single-ion
      monitoring at m/z 52 and m/z 53 for final work. A mobile phase consisting of
      ammonium sulfate and ammonium hydroxide was used, and a simple chelation
      procedure with EDTA was followed to stabilize the Cr(III) species in standard
      solutions. ICP-MS results indicated the feasibility of using chromium isotope m/z
      53 instead of the more abundant m/z 52 isotope due to a high mobile-phase
      background most significantly from the SO+ polyatomic interference. The absolute
      detection limits based on peak-height calculations were 40 pg for Cr(III) and 100
      pg for Cr(VI) in aqueous media by HPLC-ICP-MS. The linear dynamic range extended
      from 5 ppb (ng/ml) to 1 ppm (micrograms/ml) for both species. By HPLC-ICP-AES,
      detection limits were 100 ng for Cr(III) and 200 ng for Cr(VI). Cr(III) was
      detected in NIST-SRM 1643c (National Institute of Standards and Technology
      Standard Reference Material, Trace Elements in Water) by HPLC-ICP-MS at the 20
      ppb level.

PMID- 7581852
TI  - General method for determining ethylene oxide and related N7-guanine DNA adducts
      by gas chromatography-electron capture mass spectrometry.
AB  - A 112-micrograms sample of DNA was spiked with 103 pg of N7-(2'
      hydroxyethyl)guanine and 100 pg of N7-(2'-hydroxyethyl-d4)guanine, the internal
      standard. The sample was subjected to the following sequence of steps: heating at
      100 degrees C, precipitation of the DNA with HCl, reaction with nitrous acid to
      form the corresponding xanthines, reaction twice with pentafluorobenzyl bromide
      (first to derivatize NH, then OH), solid-phase extraction on silica and detection
      by gas chromatography-electron capture mass spectrometry. The absolute, overall
      yield of final product for both the analyte and internal standard was 9.7%.
      Conveniently, the three chemical reactions are conducted sequentially in the same
      vial and, aside from a washing step, are separated only by evaporations.
      Corresponding N7-guanine methyl, phenyl and styrene oxide adducts were detected
      at about the 50-ng level by the procedure, to indicate the generality of the
      method.

PMID- 7581853
TI  - Liquid chromatographic determination of the antibiotic fumagillin in fish meat
      samples.
AB  - A procedure for the determination of fumagillin, an antibiotic of Aspergillus
      fumigatus in fish meat samples, using reversed-phase high-performance liquid
      chromatography is described. Liquid chromatography was performed on an
      octadecylsilane column using acetonitrile-water-phosphoric acid solution as
      mobile phase, with detection at 350 nm. Two different types of sample preparation
      were developed, clean-up and enrichment, and the limits of quantification were
      100 ng/g and 5 ng/g, respectively, in fish meat. The recovery was 75 +/- 3% in
      the concentration range 100-500 ng/g. To introduce the methodology and
      demonstrate its usefulness, a practical experiment was performed. Trouts fed with
      fumagillin were examined for elimination of fumagillin. After 24 h, the
      concentration was shown to decrease to below 100 ng/g.

PMID- 7581854
TI  - Improved high-performance liquid chromatographic method for the determination of
      polyamines as their benzoylated derivatives: application to P388 cancer cells.
AB  - A simple reversed-phase HPLC method was developed for the determination of eight
      polyamines or monoacetylpolyamines, as their benzoylated derivatives. Interfering
      products, inherent to the benzoyl chloride derivatization technique (benzoic
      acid, methyl benzoate and benzoic anhydride), were identified. A new
      derivatization procedure for their total elimination was developed without any
      loss of sensitivity and selectivity. Not only the HPLC method was validated, but
      also the choice of an internal standard was investigated. The results show that
      it is possible to use this HPLC assay to determine the polyamine content in P388
      cancer cells. Furthermore, the method is now being used to evaluate the uptake of
      various polyamines by P388 cancer cells and by other cancer and parasitic cells.

PMID- 7581855
TI  - Enrichment and analysis of desmosine and isodesmosine in biological fluids.
AB  - A method has been developed for the enrichment and analysis of the elastin
      crosslinks, desmosine and isodesmosine, in biological fluids and tissues. It is
      adapted from published methods, offering improved recovery, sensitivity,
      resolution, and speed of analysis. Samples were hydrolyzed in 6 M HCl, after
      which the desmosines were enriched by CF1 cellulose chromatography and analyzed
      by HPLC with a C18 column. Isodesmosine and desmosine were quantitated based on
      absorbance at 275 nm, with a limit of detection of approximately 30 pmol and
      recovery of approximately 66% in urine. Their tR values on our HPLC system were
      approximately 9 and 12 min, respectively. This method was used to evaluate the
      daily and weekly variation in the concentrations of desmosine and isodesmosine in
      human urine. The results suggest that this method can be used to process large
      numbers of biological samples for analysis of desmosine and isodesmosine.

PMID- 7581856
TI  - Recombinant proteins L and LG: efficient tools for purification of murine
      immunoglobulin G fragments.
AB  - In order to improve antibody purification methods, recombinant proteins L and LG
      were tested in the purification of murine monoclonal immunoglobulin G (IgG) and
      its fragments. After affinity constant evaluation in different buffer systems,
      high-performance affinity chromatographic columns were prepared by coupling the
      proteins to Affi-prep 10 resin and tested with eight different murine monoclonal
      antibodies and their fragments of different isotypes. Affinity chromatographic
      experiments confirmed radioimmunoassay results showing that protein L bound 75%
      of the tested antibody fragments whereas protein LG had affinity for all the
      tested fragments. These results demonstrate that protein LG is the most powerful
      Ig-binding tool so far described.

PMID- 7581857
TI  - Biological and biophysical characterization of recombinant soluble human E
      selectin purified at large scale by reversed-phase high-performance liquid
      chromatography.
AB  - A first step in the development of a high-throughput screening assay for
      antagonists of human E-selectin is the purification and characterization of the
      selectin. In the present paper we describe a single-step, rapid, reversed-phase
      HPLC purification protocol for the recombinant, soluble form of human E-selectin
      (rshE-selectin) produced in Chinese hamster ovary cells. The procedure resulted
      in high protein yields with recoveries of greater than 98%. Characterization of
      the reversed-phase purified rshE-selectin showed this product to be analogous to
      rshE-selectin purified using conventional chromatographic techniques with respect
      to biological activity and molecular shape. However, the carbohydrate composition
      of reversed-phase purified rshE-selectin, which had been variable with
      conventionally purified material, was found to be constant across several
      isolations. The protocol described herein eliminated the high mannose component
      associated with previously purified rshE-selectin and provided a uniform
      carbohydrate composition for additional experimental studies, such as NMR. This
      fact, coupled with the high yield and simplicity of the present purification
      scheme are distinct advantages over those previously published. It is expected
      that other mammalian selectins, such as P-selectin and L-selectin, would also be
      amenable to reversed-phase HPLC purification.

PMID- 7581858
TI  - Simultaneous determination of retinyl esters and retinol in human livers by
      reversed-phase high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method for the simultaneous
      determination of retinol and retinyl esters in human liver samples is presented.
      The free retinol and the prevalent retinyl esters (retinyl palmitate, oleate and
      stearate) are resolved within less than 30 min, using an octasilyl (C8)
      substituted column and an isocratic elution with methanol-water as mobile phase.
      This method allows to determine in duplicate all retinyl ester concentrations in
      small liver samples (3-10 mg of fresh tissue). The results obtained from thirteen
      patients without liver disease are described.

PMID- 7581859
TI  - Capillary electrophoresis as a clinical tool. Determination of organic anions in
      normal and uremic serum using photodiode-array detection.
AB  - We report the use of free solution capillary electrophoresis to identify and
      quantify low-molecular-mass compounds found in normal and uremic serum as well as
      in hemodialysate fluid. The method reported provides a multicomponent analysis,
      allowing a single-step screening for more than 19 metabolites in less than 16
      min. Serum samples from healthy individuals and from patients who have been
      diagnosed with chronic renal failure are analyzed using a borate buffer system at
      pH 9.0, and an extended light path capillary. Several ionic sample constituents
      are identified by electrophoretic mobility, UV spectra, and spiking with
      authentic standards. An analysis of the relative concentration of several
      metabolites, including hypoxanthine, pseudouridine, hippuric acid, and uric acid
      is presented. Each of these four metabolites is found in both normal and uremic
      serum samples (limits of detection 1 to 6 microM). Moreover, each of these
      metabolites is present at significantly elevated levels in uremic patients. The
      method reported is shown to have promising clinical utility for profiling serum
      sample constituents, and for quantitative determination of a few important
      metabolites.

PMID- 7581860
TI  - Reversed-phase high-performance liquid chromatography--photodiode-array analysis
      of alkaloid drugs of forensic interest.
AB  - A reversed-phase high-performance liquid chromatography-photodiode-array method
      for the analysis of 23 drugs of forensic interest is presented. The separation
      method development was based on mobile-phase optimisation, temperature control
      and use of three ODS stationary phases. Multiwavelength detection and
      quantitation was performed at 225, 232, 239, 254, 275 and 289 nm. Absorbance
      rationing proved to be very helpful for the identification of these drugs.
      Recognition of the analysed compounds was achieved by means of correlation of
      retention time and absorbance ratios. The method was directly applied to the
      analysis of illicit heroin and cocaine samples and to the analysis of
      pharmaceutical preparations containing codeine.

PMID- 7581862
TI  - Determination of xanomeline and active metabolite, N-desmethylxanomeline, in
      human plasma by liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry.
AB  - We have developed a method for the determination of xanomeline and its
      pharmacologically active N-desmethyl metabolite. The validated method uses hexane
      to extract xanomeline and its N-desmethyl metabolite from basified plasma. The
      hexane extract is dried, reconstituted, and analyzed using a liquid
      chromatographic-atmospheric pressure chemical ionization tandem mass spectrometry
      system. The method was developed to support phase II clinical trials and has
      proven to be extremely sensitive, fast, and rugged. The method has a limit of
      quantitation of 75 and 200 pg/ml plasma for xanomeline and the N-desmethyl
      metabolite, respectively. Sample analysis times were less than 3 min from one
      injection to the next.

PMID- 7581861
TI  - Liquid chromatographic determination of urinary 2-thiothiazolidine-4-carboxylic
      acid, a biomarker of carbon disulphide exposure.
AB  - An effective gradient high-performance liquid chromatographic method for baseline
      separation of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA), with
      photodiode array detection at 271 nm was described. o-Methylhippuric acid was
      used as an internal standard (I.S.). A 1-ml urine sample was saturated with 300
      mg of sodium sulphate, acidified with 100 microliters of 6 M hydrochloric acid,
      extracted twice with 2 ml of diethyl ether, and after evaporation, the residue
      was taken up in 1 ml of 0.1% (v/v) phosphoric acid. The two mobile phases used
      for gradient elution were: (A) 10 mM ammonium dihydrogenphosphate (pH 3.5) and
      (B) same concentration of buffer but containing 20% (v/v) of methanol (pH 4.8).
      The flow-rate was set at 1.0 ml/min. TTCA and I.S. were detected at 2.2 and 9.1
      min, respectively. The method was validated with urine samples collected from
      normal subjects and workers occupationally exposed to carbon disulphide. The
      present method enables the detection of urinary TTCA at a concentration of 0.025
      mg/l. Analytical recovery and reproducibility generally exceeded 90%. The
      proposed method is considered more sensitive, specific and reliable than other
      existing methods.

PMID- 7581863
TI  - Determination of the anti-platelet-activating factor BN-50727 and its metabolites
      in human plasma by high-performance liquid chromatography-solid-phase extraction.
AB  - A sensitive and selective HPLC-solid-phase extraction procedure was developed for
      the determination of platelet-activating factor antagonist BN-50727 and its
      metabolites in human plasma. The procedure consisted of an automated solid-phase
      extraction of the drug and metabolites on disposable propylcarboxylic acid
      cartridges, followed by on-line chromatographic separation. The method was linear
      from 3.75 to 2400 ng/ml and the limit of quantitation for BN-50727 in plasma
      samples was 3.75 ng/ml. The within-run precision of the method, expressed as
      relative standard deviation, ranged from 2.1 to 8.1%. The accuracy, expressed as
      relative error, ranged from -3.5 to 4.0%. For the main metabolite, the O
      demethylated BN-50727 product, the method was linear from 7.5 to 2400 ng/ml and
      the limit of quantitation in plasma was 7.5 ng/ml. The within-run precision
      ranged from 2.1 to 11.0% and the accuracy from -5.3 to 1.1%. This paper describes
      the validation of the analytical methodology for the determination of BN-50727 in
      human plasma and also of its metabolites. The method has been used to follow the
      time course of BN-50727 and its metabolites in human plasma after administration
      of single and multiple doses.

PMID- 7581864
TI  - Quantitative determination of perphenazine and its metabolites in plasma by high
      performance liquid chromatography and coulometric detection.
AB  - An accurate, reliable method has been developed for the therapeutic monitoring of
      perphenazine (PPZ) and its major metabolites in human plasma samples. Steady
      state plasma levels of PPZ and its metabolites were quantitated for 30 elderly
      patients (mean age: 75) undergoing concurrent treatment with nortriptyline (NT)
      and PPZ, doses ranging from 4 to 32 mg/day for PPZ. The assay was suitable with
      patients on concurrent medications, and smaller patient plasma volumes (1 ml)
      were used indicating sufficient sensitivity and specificity. After plasma
      extraction and separation on a Nucleosil 5-microns C18 column, the recoveries
      (mean +/- S.D.) of PPZ and its metabolites were determined; perphenazine 92 +/-
      7.5%, deshydroxyethylperphenazine 81 +/- 7.2%, perphenazine sulfoxide 68 +/-
      6.4%, and 7-hydroxyperphenazine 45 +/- 5.5%. The assay also had limits of
      quantitative detectability for PPZ and its metabolites as follows: perphenazine
      0.5 ng/ml, deshydroxyethylperphenazine 1.0 ng/ml, perphenazine sulfoxide 0.5
      ng/ml, and 7-hydroxyperphenazine 5 ng/ml. Inter-assay reproducibility (C.V.) for
      the quality controls and patient samples ranged from 18.8 to 2.4%. The
      sensitivity and reproducibility of this method should improve PPZ therapeutic
      drug monitoring and research on interactions in depressed geriatric patients.

PMID- 7581865
TI  - Simultaneous determination of citalopram and its metabolites by high-performance
      liquid chromatography with column switching and fluorescence detection by direct
      plasma injection.
AB  - High-performance liquid chromatography with a successive column-switching
      technique was developed for simultaneous determination of citalopram and its four
      metabolites in plasma. Plasma samples were injected directly, and the target
      compounds were purified and concentrated with an inexpensive commercial octadecyl
      guard column. Then, the six-port valve was switched, and the compounds retained
      in the column were eluted by the back-flush method using 20 mM phosphate buffer
      (pH 4.6)-acetonitrile (70:30, v/v) containing 0.1% diethylamine and separated
      with an ODS column. The compounds were assayed with a fluorescence detector at an
      excitation wavelength of 249 nm and an emission wavelength of 302 nm. At least 30
      plasma samples could be treated with an octadecyl guard column. The limits of
      quantitation of this method were 2.0 ng/ml for citalopram, desmethylcitalopram,
      didesmethylcitalopram, citalopram propionic acid and citalopram N-oxide. This
      method was applied to a pharmacokinetic study in dogs and a toxicokinetic study
      in rats.

PMID- 7581866
TI  - High-performance liquid chromatographic analysis of pindolol enantiomers in human
      serum and urine using a reversed-phase cellulose-based chiral column.
AB  - Simple, sensitive and reliable high-performance liquid chromatographic methods
      are reported for the determination of pindolol enantiomers in human serum and
      urine. The methods involved a solid-phase extraction of serum and a direct
      injection of urine samples. The separation of R(+)- and S(-)-pindolol was
      accomplished on a reversed-phase cellulose-based chiral column with a mobile
      phase of 40:60 (v/v) acetonitrile-0.3 M aqueous sodium perchlorate at a flow-rate
      of 0.5 ml/min. The detection was achieved by monitoring the fluorescence emission
      of pindolol enantiomers at 310 nm with excitation at 270 nm. The limits of
      detection were 1.2 ng/ml of R(+)- and 4.3 ng/ml of S(-)-pindolol in serum, and 21
      ng/ml of R(+)- and 76 ng/ml of S(-)-pindolol in urine. The external standard
      method was used for quantitation. The methods have been applied to the analysis
      of human serum and urine samples in a pharmacokinetic study.

PMID- 7581867
TI  - New solid-phase extraction for an improved high-performance liquid
      chromatographic procedure for the quantitation of halofantrine and
      monodesbutylhalofantrine in blood or plasma.
AB  - A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC)
      method, with fluorimetric detection, for the simultaneous measurement of
      halofantrine and desbutylhalofantrine in human plasma or whole blood is
      described. Sample preparation involved protein precipitation, followed by an
      efficient solid-phase extraction on a C8 cartridge. Analytes were isolated from 1
      ml of the biological fluids and recovered by a 2% acetic acid in ethyl acetate
      solution. Chromatographic separation was carried out on a LiChrospher 60 RP
      select B, C8 bonded phase (5 microns particle size, 25 cm x 4 mm I.D.) using a
      mobile phase of water-acetonitrile (35:65, v/v) containing triethylamine (1%) and
      adjusted to pH 4 with orthophosphoric acid. The total run time was 14 min.
      Relative standard deviations of the intra-and inter-assay precisions were less
      than 5.9%. Assumption of linearity was investigated by studying the y-residuals
      and by ANOVA (analysis of variance). Because of the wide range of calibration
      (0.1 to 2.0 microgram/ml) variances were non-homogeneous (Hartley's test) and the
      weighted regression line was computed in order to allow pharmacokinetic studies.
      Accuracy was tested using a t-statistic. Limits of decision, detection and
      quantification were realized from an analysis of the blanks. Application of the
      method to clinical specimens was demonstrated.

PMID- 7581868
TI  - Separation of juvenile hormone metabolites with a silica-based gel permeation
      column.
AB  - Metabolites of juvenile hormone (JH) III, JH acid, JH diol and JH acid diol in an
      aqueous solution were separated by gel permeation chromatography using an
      UltraSpherogel SEC 2000 column. Each metabolite was eluted in an inclusion volume
      in the order JH acid diol, JH acid and JH diol. Although JH was the last compound
      eluted, it was co-eluted with a JH-binding protein (JHBP) when JHBP was present
      in the solution. Using this method, in vivo and in vitro JH catabolism studies
      were performed in the fifth stadium larvae of Bombyx mori.

PMID- 7581870
TI  - Determination of ochratoxin A in bile of swine by high-performance liquid
      chromatography.
AB  - A method for the determination of low concentrations of the mycotoxin ochratoxin
      A (OA) in bile of pigs is described. OA was extracted with acidified chloroform
      and the extract was purified on a silicagel cartridge, followed by liquid-liquid
      partition. OA was determined by high-performance liquid chromatography with
      fluorescence detection. The detection limit was 0.3 ng/ml, the mean recovery was
      84%. An enzyme-linked immunosorbent assay proved to be suitable for confirmation
      of positive results. Because of the low detection limit, biliary elimination of
      OA in pigs fed with low-contaminated feedstuffs can be examined by this method.
      This is an important requirement for the study of pharmacokinetic profiles of OA.

PMID- 7581869
TI  - Selective removal of immunoglobulin E from rat blood by membrane-immobilized
      antibody.
AB  - We examined the suitability of an immunoaffinity membrane [rabbit IgG specific
      for rat immunoglobulin E (IgE) immobilized on a cellulose membrane] for removing
      IgE from rat blood passed through a simple extracorporeal circulatory system. To
      determine the concentration of IgE in the blood, we also developed a highly
      sensitive chemiluminescence enzyme immunoassay for rat IgE. The IgE levels in the
      outlet blood from the immunoaffinity membrane module decreased to 30% of the
      initial concentration within 30 min.

PMID- 7581871
TI  - Rapid microsample analysis of imipramine and desipramine by reversed-phase high
      performance liquid chromatography with ultraviolet detection.
AB  - A rapid and highly sensitive HPLC assay method was developed to measure small
      amounts of imipramine and its major metabolite, desipramine. The assay involved
      simple extraction procedures using clomipramine as the internal standard. The
      mobile phase consisted of acetonitrile (60%) and 0.01 M triethylamine in
      distilled water (40%) with the pH adjusted to 3.0. Separations were achieved on a
      C18 column and the effluent measured for UV absorption at 260 nm. The
      chromatographic separation was excellent, with no interference from endogenous
      serum constituents. This assay was suitable for measuring drug concentrations in
      the range of 10-1000 ng/ml using a 0.1-ml serum sample. The method was applied to
      a drug disposition study in transgenic mice with increased plasma alpha 1-acid
      glycoprotein.

PMID- 7581872
TI  - High-performance liquid chromatographic determination of evodiamine in rat
      plasma: application to pharmacokinetic studies.
AB  - A previously published simple and sensitive high-performance liquid
      chromatographic method for determination and identification of rutaecarpine in
      rat plasma was used for evodiamine determination. However, the ultraviolet
      detection was not 344 nm, but 227 nm. The method was applied to a pharmacokinetic
      study of evodiamine in rats after 2 mg/kg intravenous administration. A biphasic
      phenomenon with a rapid distribution followed by a slower elimination phase was
      observed from the plasma concentration-time curve. Compartmental analysis yielded
      a two-compartment model.

PMID- 7581873
TI  - Proceedings of the 5th Annual Frederick Conference on Capillary Electrophoresis.
      Frederick, Maryland, October 25-26, 1994.

PMID- 7581875
TI  - Poly(ethyleneoxide) for high-resolution and high-speed separation of DNA by
      capillary electrophoresis.
AB  - Capillary electrophoresis (CE) with polyacrylamide gels has already been
      demonstrated to allow single-base resolution of single-stranded DNA. However,
      linear polyacrylamide is not an ideal matrix because of a high viscosity and
      difficulties in preparing the polymer with well defined pore sizes.
      Alternatively, poly(ethyleneoxide) (PEO) with a large range of molecular masses
      from 300,000 to 8,000,000 is available commercially. In addition, it is easy to
      prepare homogeneous solutions to provide highly reproducible separation
      performance with sufficient resolution. Single-base resolution of double-stranded
      DNA between 123 and 124 base pairs can be achieved by the use of homogeneous
      matrices prepared from PEO (2.5% M(r) 8,000,000), and even better resolution is
      achieved by using mixed polymer matrices. With further work, it should be
      possible to change the fractions and the total amounts of polymers to achieve
      even higher resolution for different samples with different size ranges of
      fragments. Another advantage of mixed polymer matrices is that relatively high
      resolution can be obtained while maintaining a relatively low viscosity compared
      to linear polyacrylamide with identical contents of formamide and urea, which
      makes it easier to fill these matrices into small capillaries.

PMID- 7581877
TI  - Determination of ephedrine compounds in nutritional supplements by cyclodextrin
      modified capillary electrophoresis.
AB  - Capillary electrophoresis was utilized for the separation, identification, and
      quantitation of ten stereoisomers in the ephedrine family. Chiral discrimination
      was accomplished through the use of hydroxypropyl-beta-cyclodextrin, and
      separation was enhanced at pH 2 in the presence of tetramethylammonium chloride
      and sodium dodecyl sulfate. Calibration plots of the ephedrines were linear over
      the range 4-100 micrograms/ml. This method was used in the analysis of
      nutritional supplements that contain Ma Huang, a Chinese herbal preparation that
      is made from plants in the genus Ephedra.

PMID- 7581874
TI  - Speciation of organotin compounds by capillary electrophoresis using indirect
      ultraviolet absorbance detection.
AB  - Capillary electrophoresis (CE) with indirect photometric detection was
      investigated for the separation of organotin species. Compounds such as
      dimethyltin (DMT), dibutyltin (DBT), and tributyltin (TBT) are important
      pollutants in the aqueous environment and techniques are needed to analyze
      directly aqueous environmental samples quickly and economically. By adjusting the
      mobile phase to pH 2.65 by HCl, tributyltin, dibutyltin and dimethyltin in
      aqueous solutions were separated by capillary electrophoresis using indirect
      ultraviolet (UV) absorbance detection. Pyridine was used as the UV absorption
      additive at 254 nm and separation was achieved in 6 min. Peak tailing obtained at
      higher pH suggests strong interaction between the dimethyltin cation and the
      negatively charged capillary wall. Cetyltrimethylammonium bromide (CTAB) was
      added to the mobile phase to improve the peak shapes when the pH of the mobile
      phase was greater than 3.5. Separations of organotin species in mobile phases
      with or without CTAB were compared. The change of electrophoretic mobility in
      mobile phases with different pH values indicates that DMT and DBT start to
      undergo hydrolysis at a pH 3.0. It was also found that the choice of the buffer
      anions is critical in the separation of the tin compounds as complexes appear to
      form with DMT and DBT in the presence of oxalate and citrate.

PMID- 7581876
TI  - Analysis of a ribonuclease H digestion of N3'-->P5' phosphoramidate-RNA duplexes
      by capillary gel electrophoresis.
AB  - Phosphodiester oligonucleotides (ODNs) and their analogs are presently being
      investigated as potential antisense therapeutics in the treatment of viral
      infections and various forms of cancer. here, we would like to report results
      from an investigation of activity for a ribonuclease H (RNase H) mediated RNA
      digestion assay in the duplexes formed by an ODN or the ODN analog, N3'-->P5'
      phosphoramidate (3'-phosphoramidate), and complimentary RNA strands. Capillary
      gel electrophoresis (CGE) proved to be an effective method for determining RNA
      hydrolysis in the presence of RNase H. RNA and an ODN or RNA and a 3'
      phosphoramidate were hybridized in a Tris-HCl, MgCl2 buffer at room temperature
      (RT) and incubated with RNase H. Digestions were carried out at RT or at 37
      degrees C. Control samples were unhybridized RNA with RNase H, RNA without RNase
      H, and duplexes (RNA-ODN or 3'-phosphoramidate) without RNase H. All controls
      were incubated in Tris-HCl, MgCl2 buffer, and sample aliquots were analyzed at
      various time intervals. A homodecamer, (dT)10, was used as an internal standard
      to determine the relative migration time of the RNA strand. The final digestion
      products for the duplexes and the various controls were monitored by CGE. In
      addition, polyacrylamide gel electrophoresis (PAGE) was used in conjunction with
      Stains-All (staining) and a densitometric analysis to verify CGE results.

PMID- 7581878
TI  - Determination of a cyclic guanine monophosphate phosphodiesterase inhibitor (SCH
      51866) in rat serum using capillary zone electrophoresis.
AB  - A capillary zone electrophoretic (CZE) assay was developed for the determination
      of cis-5,6a,7,8,9,9a-hexahydro-2-[4-(trifluoromethyl)phenylmethyl]-5-methyl -
      cyclopent[4,5]imidazo[2,1-b]purin-4(3H)-one, SCH 51866 (I), a cyclic guanine
      monophosphate phosphodiesterase inhibitor, in rat serum using acetonitrile
      deproteination as a clean-up step before injection. The calibration curve was
      linear over a serum concentration range of 0.5 to 10 micrograms/ml serum with a
      correlation coefficient (r) > 0.99. The limit of quantitation (LOQ) was
      established at 0.5 micrograms/ml. Fifty microliters of serum were used for
      analysis, which allowed serial bleeding (8 samples) from a single rat to
      characterize the pharmacokinetic profile of I after either oral or intravenous
      drug administration. In traditional pharmacokinetic and toxicokinetic studies in
      rodents, one animal provides only one serum sample since 1 to 2 ml of sample
      volume is required for chromatographic analysis, resulting in the use of a large
      number of animals per study. This assay yields a significant reduction in the use
      of animals, hence providing a large reduction in resources and time in drug
      discovery and development.

PMID- 7581881
TI  - Determination of gabapentin in serum by capillary electrophoresis.
AB  - A rapid capillary electrophoresis method for the quantification of gabapentin, a
      new anticonvulsant drug, in serum was developed. The assay involves
      derivatization of gabapentin with fluorescamine to provide a chromophore for UV
      fluorescence detection. The migration time is about 11 min. The assay was linear
      between 0 and 20 mg/l. No other therapeutic drugs or amino acids interfered with
      the gabapentin peak. The relative standard deviation is 2.4% at a mean of 11 mg/l
      (n = 17). The mean serum level for 52 patients on this drug was 5.2 mg/l with a
      range of 0-12 mg/l.

PMID- 7581879
TI  - Assay for the dianhydride of diethylenetriaminepentaacetic acid and its major
      degradation products by capillary electrophoresis.
AB  - DTPA-DA, the dianhydride of diethylenetriaminepentaacetic acid (DTPA), is a drug
      intermediate used for preparing functional derivatives of the DTPA metal chelator
      as well as for coupling DTPA to polypeptides, antibodies and other
      macromolecules. The DTPA functions as a complexing agent for various types of
      metal ions or radionuclides for diagnostic as well as therapeutic applications. A
      capillary electrophoretic (CE) method has been developed to assess the purity of
      DTPA-DA. The method involves derivatization of the DTPA-DA to form a diamide and
      subsequent complexation of the diamide with Zn2+ followed by free solution CE
      with UV absorbance detection at 200 nm. The procedure is capable of separating
      and quantitating the two major degradation products of DTPA-DA, the monoanhydride
      (DTPA-MA) and the free pentaacetic acid (DTPA). The method was validated with
      respect to linearity, precision/reproducibility, limit of detection and accuracy.
      This procedure was shown to be a fast and reliable method to assay this highly
      reactive drug intermediate.

PMID- 7581882
TI  - Xanthine analysis in biological fluids by capillary electrophoresis.
AB  - Xanthine, a precursor of uric acid, is measured here in serum, urine, and
      cerebrospinal fluids by capillary electrophoresis (CE) after deproteinization
      with acetonitrile. The migration time is about 7.5 min with a minimum detection
      limit of 0.4 mg/l. Different purines and pyrimidines did not interfere with the
      determination. The method demonstrates the suitability of the CE for
      determination of small molecules present in a complex matrix at levels of ca.
      1mg/l. It also demonstrates that acetonitrile deproteinization is a simple and
      effective method for preparing samples for CE, allowing a large volume to be
      introduced into the capillary.

PMID- 7581880
TI  - Separation of urinary estrogens by micellar electrokinetic chromatography.
AB  - Urinary estrogen levels are important for monitoring the normal pregnancy process
      as well as for the diagnosis of reproductive diseases. 17 beta-Estradiol and
      estrone are maintained at very low concentrations in urine and, therefore, are
      difficult to determine using standard chromatography with UV detection. In the
      present study, we describe a potential method for the determination of urinary
      estrogens (estrone, estradiol and estriol) using a solid-phase extraction and
      rapid capillary electrophoretic (CE) separations. Micellar electrokinetic
      chromatographic (MEKC) analysis was optimized by evaluating the number of
      surfactants in a 5 mM borate-5 mM phosphate separation buffer, of which sodium
      cholate (75-90 mM) was found to be optimal. Changing the hydrophobic character of
      the separation buffer with organic additives had a significant effect on the
      resolution of the three estrogens and an internal standard (d-equilenin). The
      addition of an organic additive (20% acetonitrile) was found to be necessary for
      the resolution of all components of the mixture. Substitution with 20% methanol
      provided a similar separation with better resolution but at the cost of increased
      analysis time. Analysis of two extracted urine samples from 18-weeks and 21-weeks
      pregnant women showed that, with the present technology, CE can provide adequate
      resolution and superior speed, but the sensitivity limits attainable with the
      existing technology may limit its utility to the measurement of estriol and
      estrone.

PMID- 7581883
TI  - Comparison of different techniques for the analysis of metallothionein isoforms
      by capillary electrophoresis.
AB  - We have investigated free-solution capillary electrophoresis (FSCE) and micellar
      electrokinetic capillary chromatography (MECC) separations of metallothionein
      (MT) isoforms conducted in uncoated and surface-modified fused-silica
      capillaries. At alkaline pH, FSCE rapidly resolves isoforms belonging to the MT-1
      and MT-2 charge classes. At acidic pH, additional resolution of MT isoforms is
      achieved. The use of high-ionic-strength (0.5 M) phosphate buffers can result in
      high peak efficiencies and increased resolution for some MT isoforms. Interior
      capillary surface coatings such as polyamine and linear polyacrylamide polymers
      permit separation of MT isoforms with enhanced resolution through their effects
      on electroosmotic flow (EOF) and protein-wall interactions. Improvements in MT
      isoform resolution can also be achieved by MECC using 100 mM borate buffer pH 8.4
      containing 75 mM SDS. Deproteinization of tissue cytosol samples with
      acetonitrile (60-80%) or perchloric acid (7%) produces extracts that can be
      subjected to direct analysis of MT by FSCE or MECC. We conclude that optimal
      separation of MT isoforms by capillary electrophoresis (CE) can be achieved with
      the appropriate combination of different capillaries, buffers and sample
      preparation techniques.

PMID- 7581884
TI  - Separation and detection of acidic and neutral impurities in illicit heroin via
      capillary electrophoresis.
AB  - The separation and detection of acidic and neutral impurities in illicit heroin
      using capillary electrophoresis (CE) is described. Separations were achieved
      using charged cyclodextrin modified micellar electrokinetic capillary
      chromatography. The use of the anionic beta-cyclodextrin sulfobutyl ether 1V in
      combination with sodium dodecyl sulfate significantly increased resolution.
      Improved selectivity and/or sensitivity in detection was obtained using
      photodiode array ultraviolet and laser-induced fluorescence detection. The
      phenanthrene-like heroin impurities exhibit high native fluorescence under
      krypton-fluoride laser excitation (248 nm). The limit of detection by laser
      induced fluorescence detection for one of these solutes (acetylthebaol) is 1.8
      ng/ml, 500 times more sensitive than UV. This methodology is applicable to
      analysis of both crude and refined heroin.

PMID- 7581886
TI  - Quantitative determination of serum iron in human blood by high-performance
      capillary electrophoresis.
AB  - A capillary electrophoretic (HPCE) method that can be used to quantitatively
      determine trace amounts of iron has been developed and applied to determine the
      iron level in human serum. After precipitation of serum proteins, Fe(III) in the
      serum is reduced to Fe(II) with hydroxylamine hydrochloride, and a stable Fe(II)
      1,10-phenanthroline complex is formed by adding 1,10-phenanthroline to the
      supernatant containing 2.5 mM ammonium acetate-acetic acid at pH 5.0. The Fe(II)
      1,10-phenanthroline complex, [Fe(C12H8N2)3]2+, has a very strong absorbance at
      270 nm (with a molar absorptivity of approximately 9.2.10(4)). By measuring the
      absorbance of [Fe(C12H8N2)3]2+ at 270 nm, the iron level in human serum can be
      precisely quantified. The interference from copper, a major interference in
      serum, can be totally eliminated due to the complete separation of
      [Fe(C12H8N2)3]2+ and the Cu(II)-1,10-phenanthroline complex. In addition, other
      problems that usually occurred with conventional spectrophotometric methods, such
      as co-precipitation and occlusion of iron during sample pretreatment, are
      significantly minimized due to the ability to wash the precipitate and the higher
      detection sensitivity. With this method, a single drop (10 microliters) of serum
      would be sufficient to determine the serum iron concentration. The method is
      reliable, sensitive, rapid and reproducible. Thus it is highly suitable for use
      in the clinical laboratory.

PMID- 7581885
TI  - Protein analysis by isoelectric focusing in a capillary array with an absorption
      imaging detector.
AB  - Isoelectric focusing (IEF) was successfully performed in capillary arrays with up
      to four capillaries. Separated proteins in the capillary array were detected by
      an UV absorption imaging detector. The whole analysis time for all samples in the
      capillary array was only 3 min due to the real-time imaging detector. The
      instrument was applied to analyse several protein samples including different
      human hemoglobin variants, myoglobin, transferrin, carbonic anhydrase and a
      monoclonal antibody to fluorescein. Because of good reproducibility of the
      focused pattern, unknown samples can be run simultaneously with a standard in the
      multichannel instrument and the components of unknown samples can be identified
      by comparing their zone positions to those of the standard. Minor components can
      be determined by the instrument in the presence of major components with 100
      times higher concentrations in human hemoglobin samples. This instrument could be
      a powerful analytical tool for clinical analysis and for quality control in
      pharmaceutical companies.

PMID- 7581887
TI  - Myoglobinuria detection by capillary electrophoresis.
AB  - Capillary electrophoresis was used in this study to separate urinary myoglobin
      from hemoglobin based on its electrophoretic mobility. Urine was applied directly
      without any treatment. The separation was accomplished in less than 7 min.
      Myoglobin extracted from human muscle tissues was separated, in a borate buffer
      150 mM, pH 8.7 containing 0.5% polyethyleneglycol at 6 kV, into two peaks (MI and
      MII) which were also resolved far from hemoglobin. Upon standing at room
      temperature, MII converted into MI. Horse myoglobin eluted close to MI. The
      addition of polyethyleneglycol to the buffer enhanced the separation and
      increased the peak height of myoglobin. Optimum conditions for the separation are
      discussed. The method is suitable for routine clinical analysis because of its
      simplicity and speed.

PMID- 7581888
TI  - Rapid determination of logarithmic partition coefficients between n-octanol and
      water using micellar electrokinetic capillary chromatography.
AB  - Micellar electrokinetic capillary chromatography (MECC) was evaluated as a rapid
      screening tool for the determination of logarithmic partition coefficients
      between n-octanol-water (log P(OW)). The technique is performed by
      electrochromatographing a mixture of standards of known log P(OW). The
      logarithmic capacity factor of each standard was plotted against its log P(OW) to
      form a linear calibration curve for a given set of chromatographic conditions.
      The log P(OW) of an unknown is calculated by using its chromatographically
      determined capacity factor and extracting the log P(OW) value from the
      calibration curve. The method was evaluated with a set of model compounds with
      known log P(OW). The accuracy of the method was examined and found to be within
      the limits required for screening purposes. The correlation of log P(OW) values
      determined using HPLC and MECC for some novel compounds was examined. This
      technique allows the screening of log P(OW) at a rate of four samples per hour
      with minimal sample requirements (< microgram) and with extremely small solvent
      waste generated.

PMID- 7581889
TI  - Preliminary investigations of preconcentration-capillary electrophoresis-mass
      spectrometry.
AB  - Analyte preconcentration on-line with capillary electrophoresis-mass spectrometry
      (PC-CE-MS) is described. Preconcentration cartridges were fabricated from PTFE
      tubing filled with ca. 1-2 mm bed of reversed-phase C18 HPLC packing or polymeric
      reversed-phase beads. The particle size of the stationary phase was of larger
      dimension than the internal diameter of the CE capillary. Therefore, PC-CE
      capillaries were assembled without frit material and held together by friction.
      The wide applicability of on-line PC-CE-MS is demonstrated by the analysis of
      solutions containing peptides, proteins, and synthetic analogues of putative
      metabolites of the neuroleptic agent haloperidol.

PMID- 7581890
TI  - Sample matrix effects in micellar electrokinetic capillary electrophoresis.
AB  - Several factors related to sample matrix which can influence peak height in
      micellar electrokinetic capillary chromatography were studied. The ionic strength
      of the sample did not affect greatly the peak height. High concentration of
      surfactants or organic solvents in the sample decreased the peak height. On the
      other hand, using a surfactant in the sample different from the one in the
      electrophoresis buffer or the addition of polyethylene glycol to the sample
      enhanced slightly the peak height. A high surfactant concentration in the buffer
      increased the migration time as well as the plate number and the peak height.
      Matrix effects are more profound with large than with small sample injections. In
      general, the effect of sample matrix in MECC is much less than that observed in
      capillary zone electrophoresis. It is recommended to prepare the standards in the
      same matrix as that of the sample or to add the analytes directly to the sample
      to avoid any bias in the results.

PMID- 7581891
TI  - Comparison of high-performance liquid chromatography and capillary zone
      electrophoresis in penciclovir biodegradation kinetic studies.
AB  - High-performance liquid chromatography (HPLC) and capillary zone electrophoresis
      (CZE) were used in biodegradation kinetic studies. This paper describes a rapid
      penciclovir separation using CZE with detection limits comparable to HPLC. The
      ionic-strength mediated stacking technique was employed while good resolution was
      maintained. With a shorter analysis time, comparable detection limits and no
      organic solvent consumption, CZE is a better method for penciclovir
      biodegradation studies than conventional reversed-phase HPLC (RP-HPLC).

PMID- 7581892
TI  - Separation of the eleven priority pollutant phenols by capillary zone
      electrophoresis.
AB  - Capillary zone electrophoresis (CZE) provides highly efficient separation of the
      eleven US EPA priority pollutant phenols. All of these phenols are completely
      resolved in fewer than 15 min in a 100 cm x 75 microns I.D. uncoated fused-silica
      capillary at 22.5 kV using a pH 9.8 phosphate-borate buffer. Buffer pH is the
      most critical parameter controlling resolution and separation time. A simple
      theoretical treatment greatly simplifies the pH optimization procedure. The
      effects on the separation of buffer concentration, applied voltage, and sample
      quantity injected were studied. Good calibration data were obtained for phenol
      concentrations up to 50 mg/l. Limits of detection for all phenols were less than
      1 ppm.

PMID- 7581894
TI  - Validation of the determination of amino acids in plasma by high-performance
      liquid chromatography using automated pre-column derivatization with o
      phthaldialdehyde.
AB  - A sensitive and reproducible fully automated method for the determination of
      amino acids in plasma based on reversed-phase high-performance liquid
      chromatography and o-phthaldialdehyde pre-column derivatization is described. A 5
      microns Spherisorb ODS 2 column (125 x 3 mm I.D.) was selected for routine
      determination. Over 40 physiological amino acids could be determined within 49
      min (injection to injection) and 48 samples could be processed unattended. The
      coefficients of variation for most amino acids in plasma were below 4%. We were
      also able to measure trace amounts of amino acids in plasma normally not detected
      in a routine analysis. The results obtained with the method described compared
      favourably with those of conventional amino acid analysis (r = 0.997) and were in
      excellent agreement with those of other laboratories (r = 0.999).

PMID- 7581893
TI  - High-performance liquid chromatographic system for separating sugar phosphates
      and other intermediary metabolites.
AB  - A simple method for separating intermediates of carbohydrate metabolism,
      including the difficult-to-resolve sugar phosphates, using anion-exchange high
      performance liquid chromatography is described. A gradient of decreasing borate
      concentration (10 to 0 mM) and increasing ionic strength (0 to 150 mM NH4Cl)
      separates phosphorylated sugars based on the strength of the ester complex that
      they form with borate anion. Lyophillized samples are reconstituted in a low
      ionic strength aqueous medium (5 mM triethanolamine-HCl, pH 8.1) and
      chromatographed on a commercially available anion-exchange column (Hamilton PRP
      X100). The process requires only 3 h and permits nanomole detection of the
      phosphorylated intermediates of the glycolytic and pentose shunt pathways.

PMID- 7581895
TI  - Improved virus safety and purity of a chromatographically produced factor IX
      concentrate by nanofiltration.
AB  - A virus removal system based on tangential flow filtration was introduced into a
      Factor IX production process. Beside the intended virus reduction potency of
      filter membranes, an additional purification effect could be achieved. This
      purification effect was evaluated in detail by means of sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and size-exclusion HPLC. High-molecular-mass
      impurities were retained by the membrane, thus increasing the specific activity
      of the product.

PMID- 7581896
TI  - Activity of chondroitin ABC lyase on dermatan sulfate partially degraded by
      cupric-ion-mediated free-radical treatment.
AB  - Dermatan sulfate was extracted and purified from bovine intestinal mucosa, pig
      intestinal mucosa and pigskin. Small differences in M(r), charge density and
      constituent disaccharides were detected for the three purified natural dermatan
      sulfates. Bovine intestinal mucosa dermatan sulfate was depolymerized by a
      controlled free-radical process mediated by cupric ions in the presence of
      hydrogen peroxide. Different low-molecular-mass dermatan sulfate fractions were
      produced and analysed by high-performance size-exclusion chromatography and
      polyacrylamide gel electrophoresis. The results obtained by this last technique
      strongly support the hypothesis that the free-radical process proceeds
      essentially via the destruction of disaccharide units. The partial degradation of
      dermatan sulfates by cupric-ion-mediated free-radical treatment reduces or even
      eliminates the capacity of chondroitin ABC lyase to depolymerize these
      derivatives. This was confirmed by polyacrylamide gel electrophoresis and the
      time curves of enzymatic treatments evaluated by spectrophotometry.

PMID- 7581897
TI  - Liquid-gel partitioning using Lipidex in the determination of polychlorinated
      biphenyls, naphthalenes, dibenzo-p-dioxins and dibenzofurans in blood plasma.
AB  - A method was developed for the transfer of fat, polychlorinated biphenyls (PCBs),
      naphthalenes (PCNs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) from
      blood plasma into the lipophilic gel Lipidex 5000. Subsequent elution of the gel
      separated about 70% of the fat from the analytes. Different adsorbents and
      activated charcoal were applied for further purification of the sample and
      separation of analytes. Identification and determination of the chlorinated
      compounds were made by gas chromatography with electron-capture detection (GC
      ECD) or gas chromatography-mass spectrometry (GC-MS). Recoveries were studied by
      addition of Halowax 1014 and different congeners of PCBs, PCNs, PCDDs and PCDFs
      to 50 ml of plasma. The mean recoveries of the individual compounds studied were
      72-99%. By using the liquid-gel partitioning technique emulsions were avoided.
      Concentrations of lipids in plasma obtained by the present method agreed well
      with the concentrations obtained using liquid-liquid partitioning with chloroform
      methanol.

PMID- 7581898
TI  - Simultaneous determination of malachite green and its metabolite leucomalachite
      green in eel plasma using post-column oxidation.
AB  - A rapid HPLC method with solid-phase extraction (SPE) clean-up for malachite
      green (MG) and leucomalachite green (LMG) in eel plasma was developed. MG and LMG
      were extracted with a buffered methanolic solution. The extract was subjected to
      aromatic sulphonic acid SPE. MG and LMG were eluted from the SPE column with
      methanol after a treatment with ammonia gas. The reconstituted eluate was
      analyzed on a Chromspher B column with acetonitrile-ion-pair buffer (pH 4.0)
      (6:4, v/v) as the mobile phase and detection at 610 nm after post-column
      oxidation with PbO2. The average recoveries for MG and LMG over the linear range
      of applicability (20-2500 ng/ml) were 82 +/- 1% and 83 +/- 1%, respectively. The
      limits of quantification were 5.0 micrograms/l for MG and 0.9 micrograms/l for
      LMG.

PMID- 7581899
TI  - Novel solid-phase extraction strategy for the isolation of basic drugs from whole
      blood. Preliminary study using commercially available extraction cartridges.
AB  - A novel strategy for the solid-phase extraction of basic drugs has been developed
      using commercial extraction cartridges. The procedure involves the sequential
      application of very different isolation mechanisms, viz. hydrophobic extraction
      on non-porous carbon followed by ionic extraction on a strong cation exchanger.
      This approach to extraction achieves both high recoveries and clean extracts when
      analysed by GC-MS. The potential for automation has been demonstrated using
      commercial sample preparation equipment.

PMID- 7581900
TI  - Picogram determination of iloperidone in human plasma by solid-phase extraction
      and by high-performance liquid chromatography-selected-ion monitoring
      electrospray mass spectrometry.
AB  - A very sensitive liquid chromatographic-mass spectrometric (LC-MS) method has
      been developed to quantitate iloperidone, 1, and its principal metabolite, 4-[3
      [4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-alpha-
      methylbenzenemethanol, 2, in human plasma. Iloperidone is currently used in
      clinical trials for the treatment of psychoses. The analytes were extracted from
      human plasma using mixed-mode Bond-Elut Certify cartridges and quantitated using
      selected-ion monitoring electrospray ionization mass spectrometery (SIM-ES-MS).
      No interference was observed from endogenous compounds following the extraction
      of plasma samples from six different human subjects. The limit of quantitation
      for 1 and 2 was 250 pg/ml of plasma. The standard curves were linear over a
      working range of 250 pg to 20 ng/ml. Absolute recoveries from plasma ranged from
      82 to 101% and 73 to 97% for 1 and 2, respectively. Overall intra-day precision
      ranged from 0 to 9% and 0.9 to 12.5% for 1 and 2, respectively. The method was
      found to be rugged and very reliable due to the high specificity of SIM-ES-MS.
      The results obtained from this study confirm the application of solid-phase
      extraction combined with SIM-ES-MS in quantitating basic drugs in small
      quantities in biological extracts.

PMID- 7581902
TI  - On-line solid-phase extraction of ceftazidime in serum and determination by high
      performance liquid chromatography.
AB  - A column-switching high-performance liquid chromatographic assay is described for
      the determination of ceftazidime (a third-generation cephalosporin) in human
      serum. The method does not require prior sample pretreatment. Serum is directly
      injected in a first chromatographic column for sample clean-up and extraction.
      Thereafter, using an on-line column-switching system, the drug is quantitatively
      transferred and separated on a second, analytical column followed by
      determination using ultraviolet absorption at 258 nm. The technique allows
      direct, rapid, precise, and simple determination of ceftazidime in serum over the
      range of 1-250 micrograms/ml using 12.5 microliters of serum. This method was
      applied to study the pharmacokinetics of the drug in patients undergoing vascular
      surgery.

PMID- 7581901
TI  - Characterization of cisplatin-glutathione adducts by liquid chromatography-mass
      spectrometry. Evidence for their formation in vitro but not in vivo after
      concomitant administration of cisplatin and glutathione to rats anc cancer
      patients.
AB  - After incubation of equimolar amounts of cisplatin (CDDP) and glutathione (GSH)
      in phosphate buffer pH 7.4 at 37 degrees C, we detected two CDDP-GSH adducts
      whose structures, characterized by LC-MS, corresponded to cis-[Pt(NH3)2Cl(SG)]
      and cis-([Pt(NH3)2Cl]2(mu-SG))+. The latter is a new CDDP-GSH adduct, which was
      postulated but never structurally characterized so far. Rats and patients were
      given a 15-min intravenous infusion of CDDP (10 mg/kg to rats and 25 mg/m2 to
      patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a
      bolus and 1.5 g/m2 to patients as a 15-min infusion). After the administrations,
      CDDP-GSH adducts were absent in rat and human plasma ultrafiltrates. The
      discrepancy between in vitro and in vivo findings can be explained based on
      pharmacokinetic considerations.

PMID- 7581903
TI  - Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of
      the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in
      human plasma.
AB  - Thioridazine is a commonly prescribed phenothiazine drug administered as a
      racemate and it is believed that its antipsychotic effect is mainly associated
      with (R)-thioridazine. A method based on high-performance liquid chromatography
      has been developed for the determination of the enantiomers of thioridazine and
      thioridazine 2-sulfone (THD 2-SO2 or sulforidazine) and of the enantiomers of the
      diastereoisomeric pairs of thioridazine 2-sulfoxide (THD 2-SO or mesoridazine)
      and thioridazine 5-sulfoxide (THD 5-SO) in the plasma of thioridazine-treated
      patients. The method involves sequential achiral and chiral HPLC. The limits of
      quantitation for total (R) + (S) concentrations were found to be 15 ng/ml for
      thioridazine and 5 ng/ml for its metabolites. The limits for the determination of
      the (R)/(S) ratios were found to be 60 ng/ml for racemic THD and 10 ng/ml for
      racemic THD 2-SO, THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE). The method has been
      used to determine the concentrations of the enantiomers of thioridazine and of
      its metabolites in the plasma of a patient treated with 100 mg of racemic
      thioridazine hydrochloride per os per day for 14 days. The results show a high
      enantioselectivity in the metabolism of this drug: the (R)/(S) ratios for THD,
      THD 2-SO (FE), THD 2-SO (SE), THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE) were
      found to be 3.90, 1.22, 6.10, 4.10, 0.09 and 28.0, respectively.

PMID- 7581904
TI  - Automated analysis of free and total concentrations of three antiepileptic drugs
      in plasma with on-line dialysis and high-performance liquid chromatography.
AB  - A fully automated method for determination of the free and total concentration of
      drugs with a varying degree of protein binding is described. The antiepileptic
      drugs phenytoin, carbamazepine and phenobarbitone were chosen to demonstrate the
      utility of this technique. The method was based on the ASTED system and combined
      on-line equilibrium dialysis at 37 degrees C with concentration of the dialysate
      on a trace enrichment column and HPLC determination with UV detection. The
      dialysis cell was a modification of the ASTED dialysis cell and 22% of the free
      concentration of the drugs were recovered in the recipient channel of the
      dialyser after 10 min of dialysis at 37 degrees C. The free concentration, the
      total concentration as well as the drugs protein binding could be determined. The
      method was shown to be well suited for routine monitoring of the free and the
      total concentrations of the drugs in plasma from epileptic patients.

PMID- 7581905
TI  - Determination of artemether and dihydroartemisinin in blood plasma by high
      performance liquid chromatography for application in clinical pharmacological
      studies.
AB  - A selective reproducible high-performance liquid chromatographic assay for the
      simultaneous quantitative determination of the antimalarial compound artemether
      (ARM), dihydroartemisinin (DQHS) and artemisinin (QHS), as internal standard, is
      described. After extraction from plasma, ARM and DQHS were analysed using a
      Lichrocart/Lichrosphere 100 CN stainless-steel column and a mobile phase of
      acetonitrile-0.05 M acetic acid (15:85, v/v) adjusted to pH 5.0, and
      electrochemical detection in the reductive mode. The mean recovery of ARM and
      DQHS over a concentration range of 30-120 ng/ml was 81.6% and 93.4%,
      respectively. The within-day coefficients of variation were 0.89-7.01% for ARM
      and 3.45-8.11% for DQHS. The day-to-day coefficients of variation were 2.06-8.43%
      and 3.22-6.33%, respectively. The minimum detectable concentration for ARM and
      DQHS in plasma was 2.5 and 1.25 ng/ml for both compounds. The method was found to
      be suitable for use in clinical pharmacological studies.

PMID- 7581907
TI  - High-performance liquid chromatography with fluorometric detection for monitoring
      of etoposide and its cis-isomer in plasma and leukaemic cells.
AB  - The podophyllotoxin derivative etoposide, extensively used in anticancer therapy,
      is highly protein-bound (95%) in plasma. It is a chiral drug and only the trans
      isomer is pharmacologically active. Isomerisation to the inactive cis-lactone
      occurs in plasma. The cis-lactone is often present in ultrafiltrates of plasma
      from patients treated with etoposide, therefore it is important to separate the
      isomers when free etoposide concentrations are assayed. There is reason to
      believe that free and cellular concentrations are more important for the effect
      of etoposide therapy than total plasma concentrations. A high-performance liquid
      chromatographic (HPLC) method for quantification of etoposide and its cis-isomer
      in plasma, total and non-protein-bound concentrations, and in leukaemic cells is
      described. After addition of teniposide as internal standard the drugs were
      extracted with chloroform. Etoposide, its cis-isomer, teniposide and endogenous
      substances were separated isocratically on a Spherisorb phenyl reversed-phase
      column. Detection was performed fluorometrically, lambda ex/em = 230/330 nm. Non
      protein-bound concentrations were determined after ultrafiltration. The detection
      limit for etoposide was 10 ng/ml plasma, 25 ng/ml ultrafiltrate and 10 ng/50 x
      10(6) cells. The sensitivity of the assay for the cis-lactone was twice as high
      due to higher fluorescence. The protein binding of the cis-lactone in plasma from
      ten healthy blood donors was 54.5 +/- 4.8% (mean +/- S.D.). Thus, the free
      fraction was about ten-fold higher than that of the mother compound. The assay is
      convenient and sensitive enough for the determination of free and cellular
      fractions of etoposide.

PMID- 7581906
TI  - Isolation and photodynamic effects of hematoporphyrin derivative components: a
      chromatographic analysis of the starting materials.
AB  - Twenty different fractions of hematoporphyrin derivatives (HpD) and eight
      fractions of an HpD dimer mixture were isolated utilizing isocratic reversed
      phase ion-pair high-performance liquid chromatography. These fractions were
      characterized by UV-visible and fluorescence spectrophotometry. Fluorescence
      quantum yields and photokill efficiency for each fraction in PTK2 epithelial
      cells were obtained. Results indicate that some part of the photoactivity
      exhibited by HpD may be due to impurities present in the HpD starting material,
      hematoporphyrin-IX dihydrochloride, depending on its source. It was also found
      that hematoporphyrin D, a commercial acetylated product formed during synthesis
      of HpD, contained a higher percentage of monomers than would be expected.

PMID- 7581908
TI  - Highly sensitive coupled-column high-performance liquid chromatographic method
      for the separation and quantitation of the diastereomers of leucovorin and 5
      methyltetrahydrofolate in serum and urine.
AB  - A column-switching chiral HPLC assay was developed that allows the separation and
      quantitation of the diastereomers of leucovorin (LV, 5-formyltetrahydrofolic
      acid) and its metabolite 5-methyltetrahydrofolate (METHF) in serum and urine by
      means of fluorescence detection. The analysis procedure consists of an on-line
      concentration of the folates in the HPLC system which is followed by the elution
      and separation of folates on an achiral 3-microns Microbore C18 column in (6R,S)
      LV and (6R,S)-METHF. (6R,S)-LV and (6R,S)-METHF are subsequently transferred on
      line onto a chiral 7-microns bovine serum albumin column through a Rheodyne valve
      system and are separated into their diastereometers. Time of analysis is 70 min.
      Detection limit is 5 ng/ml for each diastereometer. The within-day variation
      ranges between 3.2 and 15.8% in relation to the measured concentration. Between
      day variation is 4.4-12.1% for a concentration of 100 ng/ml for each
      diastereometer. (6R,S)-LV and (6S)-LV pharmacokinetics were assessed by analyzing
      serum and urine samples of four-healthy volunteers.

PMID- 7581909
TI  - Determination of a cardiac antiarrhythmic, tricyclic antipsychotics and
      antidepressants in human and animal urine by micellar electrokinetic capillary
      chromatography using a bile salt.
AB  - A micellar electrokinetic capillary chromatographic method based on the use of
      sodium taurodeoxycholate has been developed to detect and quantitate of 26
      tricyclic drugs. Detection limits in urine down to 4 ng/ml have been obtained.
      The method uses a simple liquid-liquid extraction and recovery of analytes
      followed by ultraviolet detection.

PMID- 7581910
TI  - Detection of 1-phenyl-N-methyl-1,2,3,4-tetrahydroisoquinoline and 1-phenyl
      1,2,3,4-tetrahydroisoquinoline in human brain by gas chromatography-tandem mass
      spectrometry.
AB  - 1-Phenyl-N-methyl-1,2,3,4-tetrahydroisoquinoline and 1-phenyl-1,2,3,4
      tetrahydroisoquinoline were detected for the first time in parkinsonian human
      brain using gas chromatography-tandem mass spectrometry (GC-MS-MS). Since these
      compounds are structural analogues of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) that produces parkinsonism in humans, they might be
      candidates for endogenous MPTP-like neurotoxins.

PMID- 7581911
TI  - Simultaneous profile analysis of plasma amino and organic acids by capillary gas
      chromatography.
AB  - A simultaneous GC analysis of more than 20 amino and nearly 30 non-amino organic
      acids abundant in plasma is for the first time possible. Isolation of the
      analytes from the plasma matrix is not necessary, keto acids do not require a
      preliminary oximation. An instantaneous derivatization of the acids with ethyl
      chloroformate takes place directly in the medium after deproteinization. Less
      than 30 min are required to prepare a plasma sample for the GC analysis.

PMID- 7581913
TI  - Matrix-assisted laser desorption mass spectrometry for the detection of
      recombinant bovine growth hormone in sustained-release form.
AB  - We employed matrix-assisted laser desorption mass spectrometry (LD-MS) to detect
      recombinant bovine growth hormone (r-bGH) in sustained-release preparations.
      After preliminary extraction in phosphate buffer, LD-MS provided a precise
      determination of the molecular mass (M(r)) of the r-bGH contained in 38 sustained
      release preparations. The hormone was characterised using enzyme immunoassay,
      immunoblotting and amino acid sequencing. Rapid detection is essential for
      analysing large numbers of samples, and for monitoring the use of r-bGH in
      zootechnical productions and its administration as a "high-tech" drug for
      therapeutic purposes.

PMID- 7581912
TI  - Quantitation of propofol in whole blood by gas chromatography-mass spectrometry.
AB  - A gas chromatographic-mass spectrometric assay, using selected-ion monitoring (GC
      MS-SIM) with thymol as internal standard, was developed for quantitating
      propofol, an intravenous anaesthetic. The method described is rapid and sensitive
      for the determination of propofol in whole blood. The sensitivity of the present
      method is 10 ng/ml. The recovery of propofol added to human whole blood in the
      concentration range 10-10,000 ng/ml ranged between 95 and 100%. A single
      extraction procedure was used with chloroform-ethyl acetate. The assay allowed
      the detection of two metabolites formed during propofol metabolism: 2,6
      diisopropyl-1,4-quinone and 2,6-diisopropyl-1,4-quinol.

PMID- 7581914
TI  - Simultaneous determination of theophylline, enoxacin and ciprofloxacin in human
      plasma and saliva by high-performance liquid chromatography.
AB  - A simple reversed-phase high-performance liquid chromatographic method has been
      developed for the simultaneous determination of theophylline, ciprofloxacin and
      enoxacin in plasma and saliva. The biological fluid samples were extracted with
      methylene chloride-isopropyl alcohol prior to isocratic chromatography on a
      Waters C18 mu Bondapak column. Ultraviolet detection was carried out at 268 nm.
      The assay is linear for ciprofloxacin and enoxacin (0.05-10 micrograms/ml), and
      theophylline (0.1-20 micrograms/ml). The assay can be used to investigate the
      interaction of these two fluoroquinolones with theophylline.

PMID- 7581916
TI  - Automation and validation of the high-performance liquid chromatographic
      radioimmunoassay method for the determination of lacidipine in plasma.
AB  - The automation and validation of the HPLC-radioimmunoassay (RIA) method for the
      determination of lacidipine are reported. The solid-phase extraction step was
      automated by the introduction of the ASPEC system. A two-column system was
      adopted for the HPLC purification. The RIA was converted from heterogeneous to
      homogeneous by the scintillation proximity assay system and automated using an
      automatic dilution system. All characteristics in terms of accuracy, precision,
      specificity, and linearity resulted similar to the manual version. The
      quantification limit was set to 40 pg/ml. The new version of the method increased
      the number of samples assayed per month two- to three-fold.

PMID- 7581915
TI  - High-performance liquid chromatographic analysis of mibefradil in dog plasma and
      urine.
AB  - The objective of the study was to develop a sensitive and specific assay for
      studying the pharmacokinetics of a novel calcium antagonist, a benzimidazolyl
      substituted tetraline derivative, mibefradil (I) in the dog. The assay involves
      liquid-liquid extraction of a biological sample, reversed-phase HPLC separation
      and fluorescence detection (lambda ex = 270 nm and lambda em = 300 nm) of sample
      components. Each sample was eluted with a mobile phase pumping at a flow-rate of
      2 ml/min. The mobile phase composition was a mixture of acetonitrile and aqueous
      solution (38:62, v/v). The aqueous solution contains 0.0393 M KH2PO4 and 0.0082 M
      Na-pentanesulphonic acid. The retention times were 10.7 min for I, and 12.2 min
      for internal standard Ro 40-6792. Calibration curves with concentrations of I
      ranging from 10 to 500 ng/ml were linear (r2 > 0.99). The detection limit for I
      was 0.5 ng/ml when 0.5 ml of plasma or urine was used. Intra- and inter-day
      accuracy and precision were within 10%. The assay was successfully applied to the
      pharmacokinetic studies of I in dogs.

PMID- 7581917
TI  - Determination of maprotiline in plasma by high-performance liquid chromatography
      with chemiluminescence detection.
AB  - A simple and sensitive high-performance liquid chromatographic method is
      described for the determination of maprotiline, an antidepressant, in plasma.
      After a single-step extraction from plasma (100 microliters) with n
      hexaneisoamylalcohol (19:1, v/v), the drug and desipramine (internal standard)
      are converted into their chemiluminescent derivatives by reaction with 6
      isothiocyanatobenzo[g]phthalazine-1,4(2H,3H)-dione, a new chemiluminescence
      derivatization reagent for amines. The derivatives are separated within 60 min on
      a reversed-phase column, TSKgel ODS-80, using isocratic elution with acetonitrile
      100 mM acetate buffer (pH 3.2), and produced chemiluminescence by reaction with
      hydrogen peroxide in the presence of potassium hexacyanoferrate(III) in alkaline
      medium. The detection limit for maprotiline added to plasma is 0.36 pmol (0.1
      ng)/ml plasma (1.5 fmol on column), at a signal-to-noise ratio of 3.

PMID- 7581919
TI  - Aspirin inhibits collagen-induced platelet serotonin release, as measured by
      microbore high-performance liquid chromatography with electrochemical detection.
AB  - A sensitive microbore high-performance liquid chromatographic method with
      electrochemical detection has been developed for the measurement of small
      quantities of serotonin (5-hydroxytryptamine; 5-HT) and its metabolite 5
      hydroxyindoleacetic acid (5-HIAA) in rabbit platelets. The limit of detection of
      5-HT is 0.1 ng/ml. To evaluate the 5-HT release from platelet suspension, the
      aggregating agent collagen was added at concentrations of 10, 30 and 100
      micrograms/ml and the 5-HT concentrations rose from the base level (11.80 +/-
      0.42 ng/ml) to 123.97 +/- 11.02, 361.96 +/- 17.90 and 470.45 +/- 35.46 ng/ml,
      respectively. Further results demonstrated that aspirin inhibits collagen-induced
      5-HT release from platelet suspension significantly.

PMID- 7581922
TI  - Improved clean-up procedure for the high-performance liquid chromatographic assay
      of clomipramine and its demethylated metabolite in human plasma.
AB  - A rapid and selective assay of clomipramine and its metabolite
      desmethylclomipramine in human plasma, based on high-performance liquid
      chromatography with UV detection has been developed. The compounds were subjected
      to solid-phase extraction, using Extrelut 1 cartridges. Recoveries ranged between
      88-95% for clomipramine, and 75-80% for desmethylclomipramine. This method has
      been used for therapeutic monitoring of clomipramine and its metabolite in
      individuals treated with this drug.

PMID- 7581921
TI  - Stability of 3,4-dihydroxyphenylacetic acid in plasma extracts assayed by high
      performance liquid chromatography with electrochemical detection.
AB  - 3,4-Dihydroxyphenylacetic acid (DOPAC) can be easily assayed by high-performance
      liquid chromatography (HPLC) with electrochemical detection at the same time as
      norepinephrine (NE), epinephrine (E), and dopamine (DA). The latter
      catecholamines are stable in perchloric acid extracts for over 6 h at 4 degrees C
      in the dark whereas DOPAC levels drop rapidly by more than 50% in 6 h at 4
      degrees C in the dark. This study investigated the effects of reducing agents
      [ascorbic acid, dithiothreitol (DTT), reduced glutathione with or without a metal
      chelating agent (diethylenetriaminepentaacetic acid or ethylenediaminetetraacetic
      acid)] on DOPAC. Extracted with alumina using 0.65 mmol/1 DTT prior to HPLC and
      electrochemical detection, DOPAC remained stable in the perchloric acid extract
      for 2 h at 4 degrees C in the dark.

PMID- 7581918
TI  - High-performance liquid chromatographic assay for xanomeline, a specific M-1
      agonist, and its metabolite in human plasma.
AB  - A reversed-phase high-performance liquid chromatographic assay (HPLC) was
      utilized for monitoring xanomeline (LY246708/NNC 11-0232) and a metabolite,
      desmethylxanomeline, in human plasma. Xanomeline, desmethylxanomeline and
      internal standard were extracted from plasm with hexane at basic pH. The organic
      solvent extract was evaporated to dryness with nitrogen and the dried residue was
      reconstituted with 0.2 M HCl-methanol (50:50, v/v). A Zorbax CN 150 x 4.6 mm
      I.D., 5-microns column and mobile phase consisting of 0.5% (5 ml/l) triethylamine
      (TEA) adjusted to pH 3.0 with concentrated orthophosphoric acid-tetrahydrofuran
      (THF) (70:30, v/v) produced consistent resolution of analytes from endogenous co
      extracted plasma components. Column effluent was monitored at 296 nm/0.008
      a.u.f.s. and the assay limit of quantification was 1.5 ng/ml. A linear response
      of 1.5 to 20 ng/ml was sufficient to monitor plasma drug/metabolite
      concentrations during clinical trials. HPLC assay validation as well as routine
      assay quality control (QC) samples indicated assay precision/accuracy was better
      than +/- 15%.

PMID- 7581920
TI  - Rapid and sensitive detection of benzodiazepines and zopiclone in serum using
      high-performance thin-layer chromatography.
AB  - We developed a rapid and sensitive method of identifying benzodiazepines and
      zopiclone in human serum using high-performance thin-layer chromatography
      (HPTLC). These drugs were developed and separated on plates within 8-11 min and
      detected by means of UV radiation and colour. Each drug was accurately identified
      by means of the values of RF x 100 and the spot colour in three systems. The
      detection limit of the benzodiazepines in serum was 0.1-0.4 micrograms/ml, except
      for cloxazolam and haloxazolam. The sensitivity was increased about ten-fold over
      the conventional method. These results suggested that the HPTLC system is useful
      for the initial detection and identification of these drugs in emergencies.

PMID- 7581924
TI  - Destiny or dalliance.

PMID- 7581923
TI  - Where is care in the brave New World? Time to get visible and political.

PMID- 7581926
TI  - Euthanasia.

PMID- 7581925
TI  - The magic of nursing: from witches and warriors to workers and wonderers.

PMID- 7581927
TI  - Pen power--doctors under scrutiny.

PMID- 7581928
TI  - Desert disaster.

PMID- 7581929
TI  - Casemix--education a top priority.

PMID- 7581930
TI  - Environmental and genetic risk factors in early human atherogenesis: lessons from
      the PDAY study. Pathobiological Determinants of Atherosclerosis in Youth.
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 pathobiology of lesion development in young
      subjects. Pathology laboratories in nine centers collected arteries and tissues
      from over 2000 persons from 15 through 34 years of age whose deaths were
      attributed to homicides, accidents, or suicides. Arteries were evaluated for
      lesions, and risk factors were analyzed in a central laboratory. Post-mortem risk
      factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin
      (diabetes), thickness of panniculus adiposus (obesity), small renal artery
      changes (hypertension) and apoprotein isoforms. This study documents the
      development of atherosclerosis at an early age. It also shows that the recognized
      risk factors for coronary heart disease are associated with lesion development in
      the arteries of these young subjects. The PDAY study has a counterpart in Japan
      where the development of atherosclerosis has been studied in young subjects. This
      Japanese study, in a population in which coronary heart disease has not yet
      become a major epidemic, has findings quite similar to the findings from the PDAY
      study. Studies of atherosclerosis in both Japan and the USA provide strong
      justification for reducing risk factors in young persons.

PMID- 7581931
TI  - Transient expression of type I collagen in glomeruli with anti-Thy-1 antibody
      induced mesangial proliferative lesions.
AB  - Glomerular expression of extracellular matrices at the protein and mRNA levels
      was examined in rats with mesangial proliferative glomerulonephritis induced by
      the intravenous administration of a monoclonal anti-rat Thy-1 antibody. In close
      association with the mesangial proliferative lesion, type I collagen was
      immunostained at day 8 but not demonstrated at day 28 in the glomeruli of the
      kidneys. Type I collagen mRNA expression prominently increased in the nephritic
      glomeruli at day 4, prior to the appearance of type I collagen protein. In
      addition, fibronectin expression was also elevated in the diseased glomeruli at
      both the protein and mRNA levels. These results indicated that glomerular,
      probably mesangial cells, change their phenotypes during this disease, to
      synthesize abnormal extracellular matrices that lead to the progression of
      glomerular sclerosis.

PMID- 7581932
TI  - Efficient and specific induction of esophageal tumors in rats by precursors of N
      nitrososarcosine ethyl ester.
AB  - Cancers and precancerous lesions of the esophagus were efficiently induced in
      rats by the simulation of a clinico-epidemiological setting; that is, the
      administration of precursors of nitrosamine. Six week old non-inbred male Wistar
      rats were given 2g/kg bodyweight of sarcosine ethyl ester hydrochloride (SEEH)
      and concurrently 0.3g/kg bodyweight of sodium nitrite (NaNO2), precursors of N
      nitrososarcosine ethyl ester (NSEE), in 2% sucrose as drinking water. Group 1
      received the precursors twice a week for 6 weeks followed by 8 weeks observation,
      and group 2, once every 3 days for 7 weeks followed by 26 weeks observation. At
      the end of treatment, no tumor had developed in the esophagus of rats in group 1,
      but the [3H]-thymidine labeling indices in both basal and superficial layer cells
      were higher than in the control group. On subsequent observation, papillomas
      appeared in group 1 (33.3%), and carcinomas in group 2 (33.3%), within 4 weeks.
      The tumors induced in group 1 were mostly papillomas and rarely carcinomas. When
      the observation was prolonged in group 2, 100% of the animals had cancer in week
      20. The pathological changes of the lesions paralleled the sequential development
      of human squamous cell carcinoma of the esophagus. Our system has the advantages
      in that papillomas and cancers can be induced in rats in a short time and the
      agents used are less toxic than preformed nitrosamines administered previously by
      gastric intubation. It would serve as a useful experimental tool to study
      premalignant lesions and cancers of the esophagus.

PMID- 7581933
TI  - Correlation between the number of apoptotic cells and expression of the apoptosis
      related antigens Fas, Le(y) and bcl-2 protein in non-Hodgkin's lymphomas.
AB  - The relationship between the number of apoptotic cells and the expression of
      apoptosis-related antigens was examined in 56 cases of non-Hodgkin's lymphomas
      and in 10 cases of reactive hyperplastic lymph nodes (RHL). Apoptosis was
      visually quantified by the in situ end-labeling (ISEL) method, and the expression
      of Fas, Le(y) antigens and bcl-2 protein was examined by immunohistochemistry.
      The expression of Le(y) antigen was observed in germinal centers of RHL and 45%
      of non-Hodgkin's lymphomas. The apoptotic cell count (AC) in follicular lymphomas
      was significantly less than that in diffuse lymphomas. The distribution pattern
      of apoptotic cells in follicular lymphomas was inverse to that in RHL. In
      follicular lymphomas, AC was lower in follicles than in interfollicular areas. In
      contrast, AC was higher in follicles than in interfollicular areas in RHL. Le(y)
      antigen-positive lymphomas showed a significantly higher AC than the negative
      cases. The Fas antigen-positive lymphomas showed a higher AC than the negative
      cases. However, AC in bcl-2 protein-positive and negative cases was not
      significantly different. These results suggest that Ley and Fas antigens appear
      to be involved in the apoptotic tendency of tumor cells in non-Hodgkin's
      lymphomas, whereas bcl-2 does not necessarily.

PMID- 7581934
TI  - Mucin histochemistry of ovarian mucinous cystadenomas expressing gastrointestinal
      characteristics.
AB  - Fifty-four cases of ovarian mucinous cystadenoma, including two cases containing
      ciliated cells representing the mullerian epithelial origin, one case admixed
      with serous adenoma component and six cases associated with mature teratoma, were
      examined for the demonstration of gastrointestinal characteristics using periodic
      acid-Schiff, alcian blue, galactose oxidase-Schiff, paradoxycal concanavalin A
      (ConA), Grimelius and Fontana-Masson stains. Of 41 endocervical-type mucinous
      cystadenomas not associated with teratoma, 34 cases (83%) showed ConA positivity,
      expressing gastrointestinal characteristics. As both cases with ciliated cells
      and the case with serous adenoma component exhibited ConA positivity, the ovarian
      surface epithelium is supposed to undergo mucinous metaplasia possessing
      gastrointestinal characteristics. As to the histogenesis of the ovarian mucinous
      tumors, the metaplasia theory is suggested.

PMID- 7581935
TI  - Pulmonary tumor thrombotic microangiopathy.
AB  - Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by widespread
      fibrocellular intimal proliferation of the small pulmonary arteries and
      arterioles in patients with metastatic carcinoma. Microscopic pulmonary tumor
      emboli have frequently occurred in patients with malignant tumors; however, few
      cases of PTTM have been reported. A rare case of a patient with gastric
      adenocarcinoma who presented with acute dyspnea and lethal respiratory failure is
      described. Histologically, diffuse fibromuscular intimal thickening causing
      luminal stenosis and obstruction but containing rather few cancer cells was
      observed in the small pulmonary arteries and arterioles. These findings were
      consistent with PTTM. Although PTTM is a rare phenomenon, PTTM should be
      considered in the differential diagnosis of acute dyspnea or pulmonary
      hypertension in patients with carcinoma.

PMID- 7581937
TI  - Pulmonary oncocytoma: report of a case in conjunction with an immunohistochemical
      and ultrastructural study.
AB  - An intra-pulmonary mass in a 51 year old Japanese woman was incidentally
      discovered in the right middle lobe. The resected tumor was grossly well
      demarcated, solid, light yellowish white in color and measured 3.0 x 2.0 x 1.5 cm
      in size. It was composed of a diffuse proliferation of large polygonal cells with
      an abundant, granular cytoplasm, and round to irregular nuclei with prominent
      nucleoli. Smaller eosinophilic cells with hyperchromatic nuclei and larger
      vacuolated cells were also observed. However, no mucin production was detected.
      There were neither argyrophilic nor argentaffin cells, and no serotonin-positive
      cells. They showed an immunoreactivity to cytokeratin and vimentin but not to
      alpha-actin. On electron microscopy, abundant microvilli, which have never been
      previously described in pulmonary oncocytomas, were observed. Occasional
      desmosomes and myelin figures as well as numerous mitochondria were also seen. No
      neurosecretory granules were present. These findings suggested that this tumor
      might have an epithelial origin from the bronchial serous gland with subsequent
      cellular degeneration.

PMID- 7581936
TI  - Pleomorphic adenoma of the breast: case report and review of the literature.
AB  - A tumor of the right breast was noticed in a 70 year old female. The tumor was
      round, 1 x 1 cm, and was encapsulated with thin fibrous tissue. The boundary was
      clear. The cut surface showed a mosaic pattern of brown and white dots and the
      texture was gritty. Histologically, glandular structures, trabecular or solid
      epithelial cell nests, myxoid, cartilaginous and osteoid areas, and one ossifying
      focus were found. Round, polyhedral or fusiform myoepithelial cells proliferated
      around the glandular structures and were dispersing into the myxoid and
      cartilaginous tissue. Myoepithelial proliferation was especially marked around
      the small glandular structure. Immunohistochemically, S-100 protein was strongly
      positive for the myoepithelial cells around the glandular structures and in the
      cartilaginous tissue. Until now, 54 cases of pleomorphic adenoma of the breast
      have been reported. In those cases, the subareolar region was a common site for
      the tumor, and pleomorphic adenoma was thought to arise from large ducts in this
      region. No Oriental patients have been reported in the literature.

PMID- 7581938
TI  - Non-X histiocytoma, similar to fibrous histiocytoma, in an infant.
AB  - A case is presented of a female infant with an atypical histiocytoma. A gradually
      enlarging brown lesion was noted on the left side of the chest at the age of 2
      weeks. Microscopic study of a biopsy revealed an ill-defined infiltration of
      spindle cells with indented nuclei. The tumor cells were positive for CD14, HLA
      DR, lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin, and negative for
      CD1, CD3, CD8, CD10, CD19, CD68 and S-100 by immunohistochemistry. Electron
      microscopy demonstrated no distinct Birbeck's granules, but aberrant granules
      were seen in a small number of cells. At 7 months of age, a nodule with similar
      histologic features was noted in the nuchal region, but was incompletely
      resected. The patient remains recurrence-free at 36 months of age. This case is
      thought to be a benign form of non-X histiocytoma.

PMID- 7581939
TI  - T cell-rich B cell lymphoma bearing Epstein-Barr virus in tumor cells: a case of
      IBL-T-like lesion following Lennert's lesion.
AB  - A case of T cell-rich B cell lymphoma (TCRBCL) with Epstein-Barr virus (EBV)
      infection in tumor cells is reported. A 50 year old male developed right cervical
      lymph node swelling in July 1988. Initial biopsy in April 1989 demonstrated many
      scattered Hodgkinoid atypical cells with Lennert's lesion. After partial
      remission following chemotherapy, the lymph nodes enlarged again, and a second
      biopsy in February 1991 showed an IBL-T-like lesion. Only a small number of
      Hodgkinoid atypical cells were still observed. After apparently, complete
      remission, the lesion soon recurred and the patient died in November 1992.
      Immunohistochemically the Hodgkinoid cells were positive for L26, but negative
      for LN2, LN3, UCHL-1, MT1, lysozyme, Ber-H2 and Leu-M1. Reactivity for
      immunoglobulins showed false-positive because of polyclonal staining. IgH
      monoclonality was detected by the polymerase chain reaction method in the first
      biopsied specimen, and by Southern blotting in the second biopsied snap-frozen
      specimen. Monoclonal TCR beta rearrangement was not detected. The Hodgkinoid
      atypical cells were positive for EBV-encoding RNA by in situ hybridization, and
      LMP-1 by immunostaining. Occasionally, EBV-bearing immunoblastic, medium sized,
      or small lymphocytic cells were also observed. This case indicates the
      possibility that EBV is related to the pathogenesis of TCRBCL.

PMID- 7581941
TI  - Parathyroid hormone-related protein: a polyhormone involved in growth,
      development and gestation.

PMID- 7581940
TI  - Genetic influences on bone turnover, bone density and fracture.

PMID- 7581943
TI  - Presence of heterogeneous thyroid-stimulating antibodies in sera from individual
      Graves' patients as shown by synthesized thyrotropin receptor peptide
      application: evidence showing two independent epitopes and a possible recognition
      of two epitopic regions by one antibody molecule.
AB  - To define the epitope(s) of stimulating thyrotropin receptor antibody (TSH-R
      Sab), we synthesized 19 oligopeptides covering almost all amino acids of the
      extracellular domain of the human TSH-R and studied these effects on the
      inhibition of one TSH-R-Sab activity. Four of the 19 peptides encompassing
      residues 31-50 (P31-20), 91-119 (P91-29), 287-304 (P287-18) and 354-367 (P354-14)
      were found to show significant TSH-R-Sab inhibition and to have similar effects
      on the other three Graves' immunoglobulins. When these peptides were applied in
      combination with P354-14 only P287-18 revealed additional effects but the other
      two combinations did not. Furthermore, sequential addition of these peptide pairs
      confirmed the additional effects of P287-18 and P354-14. Sequential peptide
      affinity gel studies were then performed. Most of the TSH-R-Sab activity in the
      unabsorbed fraction from P287-18 gel was absorbed to a subsequent P354-14 gel and
      the eluted fraction from P287-18 mostly remained unabsorbed by the P354-14 gel.
      On the other hand, most of the unabsorbed fraction from P91-29 gel remained
      unabsorbed even by the subsequent P354-14 gel. When a P354-14 affinity gel
      purified TSH-R-Sab immunoglobulin was labeled and evaluated for its binding to
      FRTL-5 cells, additions of original immunoglobulin, P354-14 and P91-29 resulted
      in significant inhibition of the binding but P287-18 did not affect either. From
      these results, it was concluded that most of the individual Graves'
      immunoglobulins contain at least two heterogeneous moieties with TSH-R-Sab
      activity, one of which binds P354-14 and the other binds P287-18. Further, P354
      14 and P91-29 were indicated to bind the same molecule of TSH-R-Sab
      immunoglobulin.

PMID- 7581944
TI  - Prevalence of thyroid dysfunction in different geriatric subpopulations from a
      moderately iodine-deficient Hungarian region. Comparative clinical and hormonal
      screening.
AB  - The aim of this study was to investigate the prevalence of thyroid dysfunction in
      different geriatric subpopulations from a moderately iodine-deficient Hungarian
      region and to compare the efficacy of clinical versus hormonal screening. A
      screening study was done on 279 chronically ill geriatric patients (Group I) and
      256 consecutive hospital admissions over 60 years of age (Group II). The method
      of clinical screening was different from those used so far: the object was not to
      search for symptoms of hypo- or hyperthyroidism but to find any sign justifying a
      further thyrotrophin-based biochemical evaluation, i.e. history of thyroid
      disease or goitre or any clinical sign of hormonal dysfunction. The rates of
      overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism and
      subclinical hyperthyroidism discovered by the hormonal screening were 2.9, 1.1,
      3.6 and 5.7% in Group I and 3.5, 2.3, 3.9 and 2.0% in Group II. The sensitivities
      of the clinical screening to suspect overt or overt+subclinical dysfunctions
      were, respectively, 0.82 and 0.64 in Group I and 1.0 and 0.7 in Group II (or 0.67
      and 0.4 if the clinical investigation was done not by an endocrinologist but by
      the medical attendants). A primarily clinical investigation-based screening would
      have spared 171/279 thyrotrophin estimation in Group I and 161/256 in Group II,
      but would have missed 2/11 overt and 11/26 subclinical dysfunctions in Group I.
      In Group II, no overt but 9/15 subclinical dysfunctions would have been lost in
      this way. Our approach of a clinical investigation-based screening was rather
      efficient in suspicion of overt thyroid dysfunction but failed to detect many
      cases with subclinical dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581945
TI  - Effect of galanin on basal and stimulated secretion of prolactin, gonadotropins,
      thyrotropin, adrenocorticotropin and cortisol in humans.
AB  - Galanin enhances both baseline and growth hormone-releasing hormone (GHRH)
      induced GH secretion both in animals and in man. Although galanin has a clear
      influence on the secretion of other anterior pituitary hormones in animals, in
      man it increases prolactin (PRL) slightly but does not affect spontaneous
      thyrotropin (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH)
      or adrenocorticotropin (ACTH) secretion. The aim of our study was to verify the
      effect of galanin on basal and releasing hormone-stimulated release of
      gonadotropins, PRL, TSH, ACTH and cortisol secretion. As GH release has been
      shown to be inhibited by corticotropin-releasing hormone (CRH), we also studied
      the effect of CRH on galanin-stimulated GH increase. The effect of porcine
      galanin (15 micrograms/kg iv infused in 60 min) alone and in combination with
      thyrotropin-releasing hormone (TRH, 200 micrograms iv bolus), CRH (100 micrograms
      iv bolus) and gonadotropin-releasing hormone (GnRH, 100 micrograms iv bolus) on
      GH, PRL, TSH, ACTH, cortisol, FSH and LH secretion in seven normal young women
      (aged 25-30 years) was studied. Galanin infusion caused an increase in serum GH
      levels (p < 0.02) but failed to modify significantly the spontaneous PRL, LH,
      FSH, TSH, ACTH and cortisol secretion. The combined administration of TRH, GnRH
      and CRH caused a significant increase in PRL (p < 0.02), LH (p < 0.02), FSH (p <
      0.02), TSH (p < 0.02), ACTH (p < 0.02) and cortisol (p < 0.05), but not in GH
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581946
TI  - Test of growth hormone secretion in adults: poor reproducibility of the insulin
      tolerance test.
AB  - The insulin tolerance test (ITT) is regarded as the most reliable provocative
      test in the diagnosis of growth hormone (GH) deficiency in adults. In the present
      study the test was evaluated by investigating the range of GH responses in normal
      adult males and females and the intra-individual reproducibility of the test.
      Sixteen healthy non-obese adults, eight males (median age 31.5 years) and eight
      females (median age 31.8 years) were tested twice with the ITT, with a minimum of
      72 h between each test. The females were tested between day 3 and day 10 of their
      menstrual cycles. Adequate hypoglycemia was achieved in all cases with a median
      nadir blood glucose of 1.3 mmol/l (range 0.8-2.0). Growth hormone in serum was
      measured by immunoradiometric assay and low values were confirmed by a different
      assay. Median peak GH concentration responses to the ITT were: in males 27.9
      micrograms/l, range 5.0-71.1 (test 1) and 30.5 micrograms/l, range 7.9-69.5 (test
      2); and in females 9.0 micrograms/l, range 4.1-17.9 (test 1) and 8.4
      micrograms/l, range 0.09-42.4 (test 2). The rise in GH concentration during the
      ITT was higher in males than in females. In the males, all stimulated GH values
      were > or = 5.0 micrograms/l. In the females, four out of 16 tests gave values
      below 5.0 micrograms/l and in one test the GH value was around the detection
      limit of the assays. There was poor reproducibility during repeated testing, with
      no correlation between the results of the two tests. The results did not
      correlate to the magnitude of the hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581942
TI  - Amniotic fluid and plasma levels of parathyroid hormone-related protein and
      hormonal modulation of its secretion by amniotic fluid cells.
AB  - Parathyroid hormone-related (PTHrP), the major mediator of humoral hypercalcemia
      of malignancy, may also regulate placental calcium flux, uterine contraction and
      fetal tissue development. In the present study, we demonstrated that the mean
      immunoreactive PTHrP concentrations in amniotic fluid at mid-gestation (21.2 +/-
      3.7 pmol/l) and at term (19.0 +/- 2.7 pmol/l) were 13-16-fold higher than levels
      measured in either fetal (1.6 +/- 0.1 pmol/l) or maternal plasma (1.4 +/- 0.3
      pmol/l) at term and equal to levels found in plasma of patients with humoral
      hypercalcemia of malignancy. In vitro studies pointed to three possible sources
      of PTHrP in amniotic fluid: cultured amniotic fluid cells, cells derived from the
      amniotic membrane overlying the placenta and placental villous core mesenchymal
      cells. Treatment of cultured amniotic fluid cells with human prolactin, human
      placental lactogen (hPL) or human growth hormone (100 micrograms/l) increased
      PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like
      growth factors I and II (100 micrograms/l), insulin (100 micrograms/l) and
      epidermal growth factor (EGF) (10 micrograms/l) increased PTHrP secretion by 53%,
      46%, 68% and 118%, respectively. The stimulation of PTHrP secretion by EGF or by
      hPL was both time- and dose-dependent. In contrast, calcitriol and dexamethasone
      (10 nmol/l) decreased PTHrP secretion by 32% and 75%, respectively. Estradiol,
      progesterone, dihydrotestosterone and human chorionic gonadotropin had no effect
      on PTHrP secretion. These findings support the notion that PTHrP may play a
      physiological role in the uteroplacental unit and demonstrate that human amniotic
      fluid cells could be a useful model for studying the regulation of PTHrP
      production and secretion by hormones and growth factors.

PMID- 7581948
TI  - A case of cyclical Cushing's disease associated with corticosteroid-binding
      globulin deficiency: a rare pitfall in the diagnosis of Cushing's disease.
AB  - We experienced an extremely unusual combination of Cushing's disease and
      corticosteroid-binding globulin (CBG) deficiency that has been reported in only
      one similar case to date. A 53-year-old woman presented at a medical clinic with
      clinical Cushing's disease. However, her plasma levels of adrenocorticotropin
      (ACTH) and cortisol were in the normal range. Six months later, during a second
      visit, a high urinary excretion of 17-hydroxycorticosteroids was found, but
      plasma ACTH and cortisol levels were normal again. Further investigation revealed
      a decreased CBG concentration. Free plasma cortisol levels were clearly elevated.
      Furthermore, the Cushing's disease of our patient was complicated by periodic
      secretion of ACTH and cortisol, with high or normal outputs of corticosteroids
      occurring alternately every 1-3 days, which explained the occasionally normal
      plasma ACTH and cortisol levels. A combination of a decreased serum CBG
      concentration and periodic secretion of ACTH can be an important pitfall in the
      diagnosis of Cushing's disease.

PMID- 7581947
TI  - Long-distance and long-term follow-up of a patient with intermittent Cushing's
      disease by salivary cortisol measurements.
AB  - Salivary cortisol is an excellent indicator of the plasma free cortisol
      concentration in normal and pathological situations. We took advantage of its
      ease of sampling, allowing multiple collections at home, to follow the course of
      a patient with Cushing's disease living in North Africa. This 48-year-old woman
      presented with a clinically moderate hypercortisolism caused by a large
      basophilic pituitary adenoma. Bilateral extension to the cavernous sinuses
      precluded surgical therapy. She went into spontaneous remission based on clinical
      signs as well as biochemical findings. During the following 2 years she
      demonstrated intermittent relapses that were treated by radiotherapy (50 Gy),
      followed by ketoconazole and then o-paraprime-dichloro-diphenyl-dichloroethane
      (Op'DDD). After a prolonged clinical remission, Cushing's syndrome again became
      active. Bromocriptine was started without effect and a new treatment with Op'DDD
      was began. Evaluation and follow-up were performed during hospitalizations and
      mainly through the measurements of salivary cortisol in more than 100 samples
      sent from North Africa by air mail to our department in Paris. Thus we were able
      to demonstrate intermittent overproduction of cortisol before any treatment, with
      periods of normal and even low values, and to follow the efficacy of therapy and
      to detect the relapses. We conclude that measurement of salivary cortisol is a
      valuable tool in difficult clinical situations such as intermittent
      hypercortisolism and remoteness between the patient and hospital.

PMID- 7581950
TI  - Expression of sex hormone-binding globulin mRNA in human ovarian cancers.
AB  - To know the role of sex hormone-binding globulin (SHBG) in the intracellular
      steroidal actions in human ovarian cancers, the expression of SHBG mRNA as a
      substitute for intracellular SHBG expression was investigated in normal ovarian
      tissues and ovarian tumors. In the present study, we used competitive reverse
      transcription-polymerase chain reaction-Southern blot analysis to evaluate SHBG
      mRNA levels. The expression of SHBG mRNA was detected in all normal ovaries and
      benign and malignant ovarian tumors analyzed. There were no significant
      differences in the mean SHBG mRNA levels among the three types of tissue. The
      expression in normal ovaries was significantly higher (p < 0.01) in premenopause,
      suggesting the predominance of a sex steroid hormone effect on ovarian SHBG
      synthesis. Relative overexpression of SHBG mRNA was observed in six out of 22
      cases (27%) of ovarian cancer (three cases of endometrioid adenocarcinoma, two
      cases of serous cystadenocarcinoma and one case of mucinous cystadenocarcinoma)
      in comparison with normal ovaries and benign ovarian tumors. There was no
      difference in expression among the clinical stages of ovarian cancers. These data
      suggest that normal human ovaries and ovarian tumors might synthesize SHBG
      intracellularly, ovarian cancers might conserve an estrogen-associated property
      via SHBG and the regulation of intracellular SHBG expression might be changed in
      some cancers.

PMID- 7581949
TI  - Subcutaneous octreotide treatment of a growth hormone-releasing hormone-secreting
      bronchial carcinoid: superiority of continuous versus intermittent administration
      to control hormonal secretion.
AB  - Diagnosis of ectopic acromegaly was made in a 21-year-old female patient who 3
      years before had undergone a right pneumectomy for a disseminated bronchial
      carcinoid. Plasma growth hormone-releasing hormone (GHRH) concentrations were
      markedly elevated (6440 ng/l; normal value < 100 ng/l), as were serum GH (187
      micrograms/l; normal < 5 micrograms/l) and plasma insulin-like growth factor I
      (IGF-I) levels (6.7 U/ml; normal < 2 U/ml). Retrospective immunohistochemical
      examination of the carcinoid tumor was positive for GHRH and the tumoral content
      of GHRH was 2130 ng/g wet weight. Subcutaneous treatment with octreotide was
      begun and first resulted in a profound inhibition of GH hypersecretion,
      normalization of plasma IGF-I and only partial reduction of GHRH concentrations.
      However, the initial dose of 3 x 100 micrograms had to be increased gradually to
      4 x 750 micrograms because of a progressive deterioration of the hormonal
      control. After 15 months of intermittent therapy, octreotide was administered by
      continuous sc infusion. This treatment improved compliance, allowed the daily
      dose of octreotide to be reduced to 1500 micrograms and normalized serum GH
      levels. A near-normalization of the plasma IGF-I concentrations was also
      obtained, whereas the suppression of plasma GHRH concentrations remained
      incomplete. Despite favorable evolution of the endocrine parameters,
      intramedullar metastases were diagnosed and required radiation therapy. This
      observation emphasizes the superiority of continuous over intermittent
      administration of octreotide in the treatment of ectopic acromegaly. It also
      shows that the somatostatin analog acts more at the pituitary level to inhibit GH
      secretion than at the site of the neuroendocrine tumor.

PMID- 7581951
TI  - Physiological concentrations of retinoic acid suppress the osteoblastic
      differentiation of fetal rat calvaria cells in vitro.
AB  - The effects of retinoic acid (RA) on osteoblastic differentiation and activity
      were studied in fetal rat calvaria cells cultured for up to 24 days. Fetal bovine
      serum used for the experiments was treated with an anion-exchange resin to remove
      endogenous RA. The depletion of RA in the treated serum was confirmed by high
      performance liquid chromatography and tritiated RA tracing. Under the culture
      conditions employed, the continuous presence of RA for 14 days at 10(-9) mol/l or
      higher decreased both alkaline phosphatase (ALP) activity on day 12 and the
      number of bone nodules on day 14 in a dose-dependent manner. Short-term (24 h)
      exposure to RA at 10(-8) mol/l, which is a physiological concentration, decreased
      and increased the levels of ALP and osteopontin mRNA on day 6, respectively.
      Retinoic acid at 10(-8) mol/l also increased the level of osteocalcin mRNA on day
      12. However, these effects were not obvious at later stages (days 18 and 24). At
      a high concentration (10(-6) mol/l), RA increased the level of osteopontin mRNA
      on day 6 and decreased the levels of ALP and osteocalcin mRNA irrespective of
      culture period. These results suggest that, at physiological concentrations, RA
      suppresses the differentiation of osteoprogenitor cells and regulates
      osteoblastic functions.

PMID- 7581952
TI  - Regulation of rat placental lactogen (rPL)-II secretion: cAMP inhibits rPL-II
      secretion in vitro.
AB  - We examined whether epidermal growth factor (EGF), interleukin (IL)-1, IL-6 and
      cAMP analogs, which regulate mouse placental lactogen II secretion, affect rat
      placental lactogen (rPL)-II secretion using a rat choriocarcinoma cell line, Rcho
      1. EGF, IL-1 and IL-6 did not affect rPL-II secretion, but 8-bromo-cAMP and
      forskolin inhibited rPL-II secretion by the 8th day of culture. The effects were
      dose dependent and the lowest concentrations of 8-bromo-cAMP and forskolin that
      significantly inhibited rPL-II secretion were 125 and 5 mumol/l, respectively.
      Cholera toxin also inhibited rPL-II secretion. The reverse hemolytic plaque assay
      for rPL-II indicated that the cells releasing rPL-II in the culture were giant
      cells and that 8-bromo-cAMP decreased the number of rPL-II-releasing cells.
      Western blot analysis of rPL-II yielded a single band at approximately 24.5 K,
      and 8-bromo-cAMP treatment significantly reduced the band intensity. Northern
      blot analysis of rPL-II indicated that 8-bromo-cAMP also reduced rPL-II gene
      expression. These findings suggest that the increase of intracellular cAMP
      accumulation results in inhibition of rPL-II secretion by decreasing rPL-II gene
      expression and inhibiting giant cell differentiation.

PMID- 7581953
TI  - Effect of restraint stress on the preovulatory luteinizing hormone profile and
      ovulation in the rat.
AB  - Plasma profiles of luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) were measured during restraint stress on the day of pro-oestrus; these
      profiles were considered in relation to ovulation rate on the next day. Rats
      bearing a permanent jugular vein cannula were subjected to restraint, which was
      started 0, 1 or 2 h before the presumed onset of the LH surge and ended just
      before the beginning of the dark period. Exposure to restraint resulted in a
      suppression of the secretion of both gonadotrophins on the day of pro-oestrus.
      Suppression of the LH surge was virtually complete (plasma LH < or = 0.2 ng/ml)
      in 15 out of 32 stressed rats, and the ovaries of these rats contained graafian
      follicles with oocytes in germinal vesicle stage. In these rats, the LH surge did
      not occur 24 h later. In the remaining 17 rats, restraint resulted in a
      considerable suppression of the LH surge. Of these rats, five had an ovulation
      rate of 100% and four ovulated partially. In unruptured follicles of the latter,
      the oocyte had not resumed meiosis and the follicle wall was not luteinized. In
      the remaining eight rats with a reduced LH surge, ovulations had not occurred and
      graafian follicles were unaffected. The results of this study indicate that
      during pro-oestrus restraint stress suppresses and does not delay the release of
      preovulatory gonadotrophins. Partial suppression of LH by restraint does not
      result in induction of meiotic resumption without subsequent ovulation or in
      luteinized unruptured follicles.

PMID- 7581954
TI  - Pups removal enhances thyrotropin-releasing hormone mRNA in the hypothalamic
      paraventricular nucleus.
AB  - Previous studies have shown that lactation and suckling alter thyrotropin
      releasing hormone (TRH) biosynthesis in hypothalamic paraventricular neurons. The
      amounts of paraventricular TRH mRNA and mediobasal hypothalamus (MBH) TRH were
      determined following removal of the pups to examine whether paraventricular TRH
      neuron activity is altered during the transition from lactation to estrous cycle.
      Paraventricular TRH mRNA and MBH TRH levels were determined by Northern blot
      analysis and radioimmunoassay, respectively. We had shown previously that after
      an 8-h withdrawal of the pups at mid-lactation the MBH TRH and paraventricular
      TRH mRNA levels are not modified. This condition was compared to one where pups
      were removed for 56 h, finding a significant decrease (46%, p < 0.005) of MBH TRH
      and a significant increase (156%, p < 0.02) of paraventricular TRH mRNA. The
      effect observed in the paraventricular TRH mRNA was correlated negatively with
      the serum corticosterone levels, a potential negative regulator of
      paraventricular TRH mRNA. The results were similar if a 1-h suckling period was
      introduced 8 h after withdrawal of the pups to induce a transient increase of
      corticosterone levels. The pattern of TRH mRNA was specific to the
      paraventricular nucleus because there was no enhancement in the preoptic area
      anterior hypothalamus. In summary, our data suggest that TRH biosynthesis in
      paraventricular neurons is slowly adjusted after withdrawal of the pups, possibly
      to prepare TRH neurons to the new secretory demands of the estrous cycle.

PMID- 7581955
TI  - Alterations in atrial natriuretic peptide gene expression during endurance
      training in rats.
AB  - Spontaneous and experimental rises of intracardiac pressure and/or volume
      increase the level of atrial natriuretic (ANP) mRNA in rat atrial tissue. There
      is expanding evidence that ANP synthesis is increased in the ventricle under such
      conditions. However, little is known with regard to the myocardial ANP synthesis
      response to physical training. In this study, plasma and atrial immunoreactive
      ANP concentrations were measured in Sprague-Dawley rats trained on a treadmill
      and compared to sedentary controls. Atrial natriuretic peptide mRNA was detected
      in the heart cavities of each group by dot-blot hybridization analysis. Physical
      training reduced the mean immunoreactive ANP plasma levels from 405 +/- 99 to 303
      +/- 45 ng/l (p < 0.05). Immunoreactive ANP in the left atrium was depleted after
      endurance training, while immunoreactive ANP concentration in the right atrium
      was unaffected. Physical training resulted in a 70% (p < 0.01) rise in ANP mRNA
      of the right atrium, while no changes in the other compartments were found. These
      data indicate that during physical training: ANP mRNA does not increase in
      ventricles; despite depletion of immunoreactive ANP in the left atrium, no
      corresponding changes of ANP mRNA are detected; and ANP mRNA increases in the
      right atrium while its immunoreactive ANP does not. These findings suggest that
      during chronic exercise the ratio between immunoreactive ANP and ANP gene
      expression in the atria may be altered.

PMID- 7581956
TI  - Plasma testosterone surge and luteinizing hormone beta (LH-beta) following
      parturition: lack of association in the male rat.
AB  - Studies examining the role of luteinizing hormone (LH) in the initiation of the
      postnatal surge of testosterone in the male rat have produced ambiguous results.
      We examined the pattern of postnatal LH secretion in the newborn male rat,
      coincident with plasma testosterone levels, using a specific monoclonal antibody
      for LH-beta. In some males, we attempted to block LH secretion and the postnatal
      testosterone surge by injecting males with a gonadotropin-releasing hormone
      (GnRH) antagonist, an LH antibody or progesterone immediately after delivery by
      cesarean section on day 22. Following injection, animals were immediately
      sacrificed (time 0) or housed in a humidified incubator maintained at 30 degrees
      C until sacrifice at 60, 120, 240, 360 or 480 min after delivery. Plasma from
      individual animals was measured subsequently for LH-beta and testosterone by
      radioimmunoassay. Results revealed a postnatal surge of testosterone which peaked
      at 2 h after delivery in males from all treatment groups. This testosterone surge
      was not accompanied by a postnatal rise in plasma LH-beta in any group.
      Administration of the GnRH antagonist or the ethanol vehicle produced a transient
      drop of approximately 25% in LH-beta levels at 60 min but did not decrease the
      postnatal testosterone surge in the same animals. Additional studies in untreated
      males and females born by cesarean section or natural birth also failed to reveal
      a postnatal rise in plasma LH-beta during the first 3 h after birth. Plasma
      levels in both sexes were significantly lower in animals delivered by cesarean
      section compared to natural birth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581957
TI  - Evidence for a role for the neurosteroid allopregnanolone in the modulation of
      reproductive function in female rats.
AB  - The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3
      alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone,
      the most potent steroid produced by neurons, on ovulation rate and sexual
      behavior in female rats. Allopregnanolone was injected intracerebroventricularly
      in rats on diestrus and proestrus and tests were done on estrus. The
      intracerebroventricular injection of allopregnanolone significantly decreased the
      number of oocytes collected on estrus (p < 0.01). To support a physiological
      involvement, antiserum to allopregnanolone was injected centrally to block the
      activity of the endogenous neurosteroid. When administered on diestrus and
      proestrus or only on proestrus, the antiserum was shown to be correlated with a
      significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats
      treated with antiserum to allopregnanolone, the lordosis intensity was augmented
      significantly as compared to controls. Finally, the possible changes of medial
      basal hypothalamus concentration of allopregnanolone throughout the estrous cycle
      and at the time of ovulation were investigated. Hypothalamic extracts were eluted
      on high-pressure liquid chromatography and allopregnanolone concentration was
      measured by radioimmunoassay. Brain cortex was used as control tissue.
      Hypothalamic allopregnanolone concentration on proestrus morning and afternoon
      was found to be significantly lower than in the remaining phases of the estrous
      cycle (p < 0.01), while no significant changes were observed in brain cortex
      concentration of allopregnanolone. The present results suggest that hypothalamic
      allopregnanolone may be involved in the mechanism of ovulation, affecting
      hormonal and behavioral events.

PMID- 7581960
TI  - Are adrenal and ovarian function normal in true precocious puberty?

PMID- 7581959
TI  - Thyroid hormones and brain development.
AB  - Thyroid hormone is a major physiological regulator of mammalian brain
      development. Cell differentiation, migration and gene expression are altered as a
      consequence of thyroid hormone deficiency or excess. The physiological role of
      thyroid hormone can perhaps be defined so as to ensure the timed coordination of
      different developmental events through specific effects on the rate of cell
      differentiation and gene expression. All triiodothyronine (T3) receptor isoforms
      are expressed in the brain and their spatial and temporal patterns of expression
      suggest unique and complementary functions for the different isoforms. Cell
      biology studies suggest a role for T3 and its receptors in oligodendroglial and
      neuronal differentiation and the control of cell death. Some of the effects on
      neuronal differentiation might be due to an action of thyroid hormone on the
      production of neurotropins and their receptors. In recent years a number of T3
      dependent genes have been identified in the rat brain, such as myelin protein
      encoding genes or specific neuronal genes, and thyroid hormone-responsive
      elements have been demonstrated in some of these genes. The identification of the
      gene network regulated by thyroid hormone during brain development, the
      elucidation of the mechanism of regulation and the clarification of the
      physiological roles of the regulated genes remain major goals for future studies.

PMID- 7581958
TI  - Adrenal androgen production in polycystic ovary syndrome.
AB  - Secondary PCOS may occur in association with disorders characterized by adrenal
      androgen excess, e.g. congenital adrenal hyperplasia. Primary PCOS is associated
      frequently with more subtle abnormalities in adrenal androgen status. However, it
      has not been established that the mild adrenal androgen occurring in PCOS is
      causally involved in the development of PCOS, although adrenal
      hyperresponsiveness to stimulation appears to be characteristic of PCOS. It
      remains to be clarified whether this is due to excess stimulation of the adrenal
      by the putative CASH, which with ACTH probably coordinates adrenal androgen
      steroidogenesis, or whether adrenal hyperresponsiveness occurs as a consequence
      of increased cortisol clearance with compensatory hypersecretion of ACTH, which
      is associated with excessive adrenal androgen production. The possibility also
      exists that the enzyme system responsible for 17-hydroxyprogesterone production
      and its conversion to androgens is excessively active and may occur as a common
      defect in the adrenal and ovaries as a consequence of a congenital disorder. For
      at least some patients, treatment with a nocturnal low-dose glucocorticoid is an
      effective form of treatment. Indeed, this is the only hormonal form of treatment
      for hirsutism that also facilitates fertility and pregnancy. It is possible that
      PCOS may occur as a consequence of any disorder in which anovulation is
      associated with normal or elevated oestrogen levels. For some patients with PCOS,
      mild adrenal androgen excess is probably primary to development of the disorder.
      Thus, a trial of treatment with low-dose glucocorticoid at night appears to be a
      reasonable option in susceptible patients who can probably be recognized by
      demonstration of an excessive androgen response to ACTH or metyrapone.

PMID- 7581961
TI  - Early polycystic ovary-like syndrome in girls with central precocious puberty and
      exaggerated adrenal response.
AB  - Exaggerated adrenal response (ExAR), i.e. hypersecretion of both 17
      hydroxypregnenolone (170HPreg) and 17-hydroxyprogesterone(17OHP) in response to
      adrenocorticotropic hormone (ACTH) stimulation, is frequently found in women with
      polycystic ovary (PCO) syndrome who had precocious adrenarche. In an earlier
      study we found an abnormal adrenal response in girls with idiopathic true central
      precocious puberty (CPP) at early stages of puberty. On follow-up it was noted
      that a significant number of girls with CPP develop PCO-like syndrome at a
      relatively young age. The aim of the present study was to determine if there is
      an association between ExAR and early PCO in girls with a history of CPP.
      Included were 49 girls with a history of CPP, 34 of whom were treated with
      gonadotropin-releasing hormone (GnRH) analog. All 49 were evaluated at full
      maturity, at ages 12.5-14 years, 0.5-4 years after menarche or resumption of
      menses. Of the 49 girls, 20 had at least 3/4 clinical signs of PCO (irregular
      menses, hirsutism, acne and obesity) and were defined as PCO-like+, whereas 29
      did not fulfil the criteria and were considered PCO-like-. Girls with a definite
      enzyme deficiency were excluded from the study. All participants underwent a
      combined iv ACTH-GnRH test at early follicular phase. The PCO-like+ girls all
      revealed ExAR, i.e. an elevated stimulated 17OHPreg of 63.4 +/- 9.6 nmol/l
      (normal 28.6 +/- 9.2 nmol/l) and a normal stimulated 17OHPreg/17OHP ratio of 7.1
      +/- 1.8 (normal 6.2 +/- 2.7), whereas all the PCO-like- had a normal adrenal
      response (30.0 +/- 8.7 and 5.3 +/- 2.0 nmol/l, respectively).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7581963
TI  - Bone mineral metabolism in girls with precocious puberty during gonadotrophin
      releasing hormone agonist treatment.
AB  - Bone mineral metabolism and mineralization before and during treatment were
      studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and
      treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate
      depot, in order to understand better the consequences of oestrogen deficiency and
      the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis
      activity. Before and after 12 months of therapy, the patients underwent a
      clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On
      day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate,
      alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding
      protein and osteocalcin levels were measured; urinary calcium, phosphate and
      hydroxyproline levels were evaluated in fasting spot samples. Trabecular and
      cortical bone mass variations, measured by dual X-ray absorptiometry in the
      lumbar spine and by dual photon absorptiometry in the radius, respectively were
      evaluated before the start and after 12 months of therapy. During treatment, a
      decrease of serum oestradiol levels from pubertal to prepubertal levels was
      observed. The GH peak following clonidine diminished significantly after 1 year.
      Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3
      decreased, although not significantly. Osteocalcin levels decreased significantly
      after 9 and 12 months of treatment, but they did not change significantly after
      calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline
      decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581962
TI  - High prevalence of abnormal adrenal response in girls with central precocious
      puberty at early pubertal stages.
AB  - Abnormal adrenal response is often observed in girls with precocious adrenarche
      (1). We studied the adrenal response in 112 girls with idiopathic true central
      precocious puberty (CPP) at early stages of puberty compared to that in 21 girls
      with normal puberty (controls). The aims of this study were to determine the
      prevalence of abnormal adrenal response at early stages of puberty, the possible
      correlation of abnormal adrenal response with pubertal signs at onset of puberty
      and with plasma androgen levels, and a possible association with the activity of
      the hypothalamic-pituitary-gonadal (HPG) axis. All participants underwent a
      combined i.v. adrenocorticotropic hormone (ACTH)-gonadotropin-releasing hormone
      (GnRH) test at Tanner stage 2-3: 62 of the CPP girls before and 50 during
      treatment with GnRH analog. The stimulated levels of 17-hydroxypregnenolone
      (17OHPreg) and the stimulated 17OHPreg/17-hydroxyprogesterone ratio were analyzed
      and compared to previously reported norms. The result revealed three patterns of
      adrenal response: normal (17OHPreg < or = 24 nmol/l and 17OHPreg/17OHP ratio < or
      = 7) in 50/112 (44.6%) CPP patients and 17/21 (80.9%) controls; exaggerated
      (17OHPreg > 24 nmol/l, 17OHPreg/17OHP ratio < or = 7) in 50/112 (44.6%) CPP
      patients and 3/21 (14.3%) controls; and non-classical 3 beta-hydroxysteroid
      dehydrogenase deficiency (17OHPreg > 24 nmol/l and 17OHPreg/17OHP ratio > 7) in
      12/112 (10.8%) CPP patients and 1/21 (4.8%) controls. The clinical features at
      onset of puberty were comparable in all girls with the CPP in spite of the
      different adrenal response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581964
TI  - Changes in systemic gonadal and adrenal steroids in asymptomatic human
      immunodeficiency virus-infected men: relationship with the CD4 cell counts.
AB  - Serum sex hormone-binding globulin (SHBG), testosterone, non-SHBG-bound
      testosterone, androstenedione, dihydrotestosterone (DHT), dehydroepiandrosterone
      (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and cortisol
      were measured in 58 homosexual men seropositive for human immunodeficiency virus
      (HIV), all clinically asymptomatic (Centers for Disease Control 1993
      classification stage A). The HIV patients were divided into four groups according
      to the CD4 lymphocyte count--group 1 (more than 500/microliters, N = 14), group 2
      (between 350 and 500/microliters, N = 16), group 3 (between 200 and
      349/microliters, N = 22) and group 4 (less than 200/microliters, N = 6)--and
      compared with 11 antibody-negative men as controls. The SHBG levels were
      significantly increased in groups 1, 2, 3 (p < 0.01) and 4 (p < 0.05) compared
      with controls, with no differences between groups of patients. Compared with
      controls, testosterone concentrations were significantly lower in group 4 (p <
      0.05) and non-SHBG-bound testosterone levels were significantly lower in groups 1
      (p < 0.05), 2 (p < 0.01), 3 (p < 0.001) and group 4 (p < 0.001); DHT and
      androstenedione levels were significantly lower in group 4 (p < 0.05) and DHEA
      levels were significantly lower in group 2, group 3 (p < 0.01) and group 4 (p <
      0.05) than in controls. Cortisol levels were significantly increased in groups 1
      and 4 (p < 0.05) and FSH and LH concentrations were not significantly higher in
      HIV-infected men than in controls. Also, the DHEA, androstenedione, non-SHBG
      bound testosterone and DHT levels were correlated with CD4 cell counts, showing
      that hypogonadism occurs as the CD4 lymphocytes decrease.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7581965
TI  - Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP
      6) administration in children with short stature.
AB  - Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a
      potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral
      administration in man. Previous data showed its activity also in some patients
      with GH deficiency. The aim of our study was to verify the GH-releasing activity
      of oral GHRP-6 administration on GH secretion in children with normal short
      stature. The effect of oral GHRP-6 (300 micrograms/kg) was compared with that of
      the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1
      microgram/kg). As the GHRH-induced GH rise in children is potentiated by arginine
      (ARG), even when administered by oral route at low dose (4 g), we studied also
      the interaction of oral GHRP-6 and ARG administration. We studied 13 children
      (nine boys and four girls aged 6.2-10.5 years, pubertal stage I) with normal
      short stature (height less than -2 SD score; height velocity more than -2 SD
      score; normal bone age; insulin-like growth factor I > 70 micrograms/l). In a
      first group of children (N = 7), oral GHRP-6 administration induced a GH response
      (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3
      micrograms/l, p < 0.0006; area under curve: 1527.3 +/- 263.9 micrograms l-1 h-1)
      which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 +/-
      4.5 vs 2.2 +/- 0.9 micrograms/l, p < 0.007; area under curve: 1429.4 +/- 248.2
      micrograms l-1 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581966
TI  - Effects of treatment with octreotide in acromegalic patients--a multicenter
      Italian study. Italian Multicenter Octreotide Study Group.
AB  - Treatment of acromegaly is effective in reversing the reduced life-span of
      patients only when serum growth hormone (GH) concentrations are lowered to less
      than 2.5 micrograms/l. Usual treatments achieve this goal in no more than 50-60%
      of patients. The effects of octreotide were studied in a prospective, open label
      study with 68 acromegalic patients enrolled in 10 Italian centers. Octreotide was
      administered sc at a dose of 100 micrograms t.i.d. for 1 year. After 3 months of
      therapy, octreotide was effective in decreasing serum GH levels below 2.5
      micrograms/l in 16 out of 64 acromegalic patients (25%). Fifteen of them had
      pretreatment GH levels below 25 micrograms/l. Insulin-like growth factor I (IGF
      I) levels normalized in about 40% of patients. No further GH reduction was
      observed after 1 year of treatment. The presence of abnormal GH responses to
      thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone was
      reduced from 54 to 24% and from 16 to 12%, respectively. Tumor shrinkage was
      observed in 50% of 26 non-irradiated patients after 12 months of treatment. Both
      basal and TRH-stimulated serum prolactin levels significantly decreased in the 11
      hyperprolactinemic patients. Although serum thyrotropin, free triiodothyronine
      and free thyroxine concentrations were not modified, a significant reduction of
      thyrotropin response to TRH was observed in the 9th month of therapy. In non
      diabetic patients, an increase of mean blood glucose levels without modifications
      of fasting morning concentrations was found. About one-quarter of the patients
      with overt diabetes mellitus had an impairment of their metabolic control. Main
      clinical symptoms of acromegaly improved in 70-80% of patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7581967
TI  - Insulin-like growth factor binding proteins in prepubertal children with insulin
      dependent diabetes mellitus.
AB  - To study the possible role of insulin-like growth factor binding proteins
      (IGFBPs) in the discrepancy between normal or only slightly retarded growth and
      substantially reduced concentrations of insulin-like growth factor I (IGF-I) in
      prepubertal children with insulin-dependent diabetes mellitus (IDDM), we measured
      the plasma concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 and free insulin
      in 24 prepubertal diabetic subjects and 12 control children. In addition, the
      growth hormone response to exercise was evaluated. The diabetic children had
      significantly decreased peripheral IGF-I levels (8.2 + 1.1 (SEM) vs 16.7 + 2.5
      nmol/l; p < 0.001), whereas the concentrations of free insulin were increased
      (217 + 14 vs 103 + 21 pmol/l; p < 0.001). The concentrations of IGFBP-1 and IGFBP
      3 were of the same magnitude in both groups. The diabetic children had
      significantly increased levels of IGFBP-2 (465 + 13 vs 416 + 14 micrograms/l; p =
      0.029), which were inversely related to the circulating IGF-I levels (r = -0.35;
      p = 0.034). The diabetic and control children had comparable growth hormone
      responses to exercise. Diabetic children with poor glucose control had even lower
      IGF-I levels than those with moderate metabolic control (6.0 + 0.8 vs 10.3 + 1.7
      nmol/l; p = 0.037). No differences could be observed in the plasma concentrations
      of various IGFBPs between these two groups of diabetic subjects. The absence in
      prepubertal diabetic children of increased IGFBP-1 levels observed in adolescent
      and adult patients with IDDM may contribute to their maintained linear growth,
      despite definitely decreased IGF-I concentrations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7581968
TI  - Resting metabolic rate, body composition and related hormonal parameters in
      growth hormone-deficient adults before and after growth hormone replacement
      therapy.
AB  - The resting metabolic rate (RMR), and body composition were assessed in 30 growth
      hormone-deficient (GHD) adults before and after 3 and 6 months of replacement
      therapy with recombinant human growth hormone (rhGH). In addition, insulin-like
      growth factor I (IGF-I), IGF binding proteins (IGFBPs) and plasma insulin were
      measured at baseline and at 6 months in relation to RMR. During 6 months of rhGH
      replacement therapy, body fat decreased from 18.2 +/- 1.5 (mean +/- SEM) to 14.3
      +/- 1.6 kg (p < 0.0001), whereas fat-free mass (FFM) increased from 53.5 +/- 3.3
      to 56.3 +/- 3.6 kg (p < 0.0001), RMR increased from 1246 +/- 92 to 1539 +/- 102
      kcal/24 h (p < 0.0001) and RMR per kilogram of FFM increased from 23.2 +/- 0.6 to
      27.4 +/- 0.5 (p < 0.0001). When RMR data were adjusted for the differences in
      FFM, it appeared that apart from the increase in FFM, other factors may play a
      role in the increase in RMR. During rhGH replacement therapy, IGF-I (p < 0.0001)
      and IGFBP-3 (p = 0.003) levels increased, whereas IGFBP-1 levels decreased
      significantly (p = 0.004). The FFM explained for about 80% of the variance in
      RMR. In addition, waist/hip ratio and plasma IGF-I contributed significantly to
      the explained variance of RMR. This study shows that in GHD adults FFM is the
      main determinant of RMR and that, next to the increase in FFM, changes in
      metabolic and hormonal parameters contribute to the increase in RMR during rhGH
      replacement therapy.

PMID- 7581969
TI  - Familial acromegaly: a specific clinical entity--further evidence from the
      genetic study of a three-generation family.
AB  - Familial acromegaly is a very rare inherited disorder, characterized by the
      clustering within a single family of several related cases with somatotroph
      adenomas and acromegaly. The causes of these dominantly inherited pituitary
      tumours remain unknown. Although these families have a clinical presentation
      distinct from that of multiple endocrine neoplasia type 1 (MEN-1), the question
      of this syndrome as being linked to the MEN-1 locus has remained open. Our aim
      was to study a three-generation family with cases of acromegaly in a mother and
      her son, to explore better the clinical presentation of the disease, its pattern
      of inheritance and to test the hypothesis of a genetic linkage to the MEN-1 locus
      using closely linked polymorphic genetic markers. The refined analysis of 15
      unaffected relatives revealed miscellaneous non-specific endocrine dysfunctions
      and the presence of multiple lipomata, as noted previously in some cases.
      Moreover, the notion of acromegalo-gigantism in the maternal grandmother and an
      incomplete penetrance appeared even more typical, suggesting that familial
      acromegaly is a specific clinical entity. Finally, under the hypotheses assumed
      for segregation analysis, no clinical, biological or genetic evidence of linkage
      to the MEN-1 locus could be retained in this family. However, these conclusions
      were limited because of incomplete penetrance and uncertain definition of the
      carrier status. Therefore, we conclude that further identification of the genetic
      predisposition to familial acromegaly might be obtained from the combined
      molecular genetic analysis of several families presenting with the same clinical
      features.

PMID- 7581970
TI  - Combined pyridostigmine-thyrotrophin-releasing hormone test for the evaluation of
      hypothalamic somatostatinergic activity in healthy normal men.
AB  - Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone
      (GH) release in man by suppression of hypothalamic somatostatin (SRIH).
      Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier
      studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response
      was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of
      PST can increase the TSH response to TRH. Six healthy young men were studied with
      the following six tests: (Test 1) 200 micrograms of TRH i.v.; (Test 2) 180 mg of
      PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4)
      100 micrograms of octreotide (SMS) i.v.; (Test 5) SMS + TRH; (Test 6) PST + SMS +
      TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin
      responses to TRH, while smaller doses of PST (60 and 120 mg) did not
      significantly increase the responses of GH and TSH. While the increased TRH
      induced prolactin response by PST was not suppressed by SMS, the increased
      responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects
      noticed a mild to moderate abdominal pain, nausea and muscular fasciculation
      after the administration of a large dose of PST administration. These data
      suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can
      augment the TSH response to TRH. However, the considerable side effects should be
      minimized before clinical application of the combined PST-TRH test.

PMID- 7581972
TI  - Signal transduction in rat myometrial cells: comparison of the actions of
      endothelin-1, oxytocin and prostaglandin F2 alpha.
AB  - The objectives of this study were to evaluate and compare the actions of
      endothelin-1 (ET-1), oxytocin, prostaglandin F2 alpha (PGF2 alpha) and inositol
      1,4,5-trisphosphate (IP3) on 45Ca2+ mobilization in permeabilized rat myometrial
      cells and to examine the activation of the inositol lipid cycle in intact
      myocytes. Cells were isolated from late pregnant rat myometrium and used as
      confluent monolayers after a single passage. All four agonists caused a biphasic
      release of 45Ca2+ from non-mitochondrial pool(s), with the rank order of potency:
      oxytocin > PGF2 alpha > ET-1 > IP3. Inhibitors of phospholipase C blocked ET-1-
      and oxytocin-promoted but not PGF2 alpha-promoted 45Ca2+ efflux. Similarly,
      heparin, an IP3 receptor blocker, failed to inhibit PGF2 alpha-induced 45Ca2+
      release while inhibiting the action of the other agonists. Endothelin-1 and
      oxytocin stimulated inositol phosphate accumulation at concentrations similar to
      those that promoted 45Ca2+ efflux, whereas about 100 times higher concentrations
      of PGF2 alpha were needed to activate this signaling pathway in intact cells. It
      is concluded that the primary action of PGF2 alpha in myometrial cells is to
      enhance Ca2+ influx, whereas oxytocin and ET-1 receptors are coupled to
      phospholipase C, generating IP3 and raising the intracellular concentration of
      free Ca2+ from intracellular as well as extracellular sources.

PMID- 7581973
TI  - Underfeeding of rat mothers during the first two trimesters of gestation does not
      alter insulin action and insulin secretion in the progeny.
AB  - It has been suggested that impaired insulin action and/or insulin secretion in
      adult mammals could be a consequence of severe food restriction during fetal
      life. We have determined to what extent glucose homeostasis and insulin action
      are modified in male offspring of rats undernourished only during the first two
      trimesters of pregnancy. Pregnant females then were assigned to one of the
      following three experimental conditions. Rats in the first group had their food
      restricted to 50% of their pregnancy intake during the first 2 weeks of
      pregnancy, after which they were allowed to eat ad libitum. Rats in the second
      group were similarly restricted during the first 2 weeks, but beginning on day 14
      of gestation were pair-fed to control rats until weaning on day 21 after birth:
      Such an experimental group was introduced because we observed that food
      restricted mothers increased their food intake significantly above control levels
      in the last week of gestation and maintained this increase into the first
      postnatal week, when they were returned to ad libitum feeding on day 14 of
      gestation. Control rats (third group) were given access to food ad libitum
      throughout pregnancy and lactation. Offspring of mothers in the three groups are
      referred to as food-restricted/ad libitum refed (RA), food-restricted/pair-refed
      (RP) and control (C) groups, respectively. From 6 weeks of age, RA males ate
      significantly more food and gained significantly more weight on a standard
      laboratory diet than control offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581974
TI  - Distinct effects of ovarian transplantation and exogenous 17 beta-oestradiol on
      cancellous bone of osteopenic ovariectomized rats.
AB  - Although 17 beta-oestradiol (E2) is known to prevent bone loss, prolonged
      administration of E2 is unable to reverse this in female rats rendered osteopenic
      by ovariectomy. To determine whether this reflects a failure to replace other
      components of ovarian function involved in bone metabolism, we compared the
      effects of administering E2 to osteopenic ovariectomized (ovx) rats with those of
      ovarian transplantation. Ovariectomy was performed in female rats. After 13
      weeks, by which time marked bone loss had occurred, one group of ovx animals
      received ovaries from donor rats, and, after a delay of 2 weeks to allow oestrus
      cycles to return, a further group received E2 5 micrograms.kg-1.day-1 for 9
      weeks. The dose of E2 was chosen as that which in preliminary studies restored
      mean serum E2 levels to that of intact female rats. The study was terminated 24
      weeks after ovariectomy. Both E2 and ovarian transplantation largely restored
      indices of oestrogenic exposure in ovx rats to those of sham-ovx animals. Animals
      receiving ovarian transplants also showed a small increase in serum progesterone
      and full restoration of serum testosterone. However, while ovarian
      transplantation also returned indices of cancellous bone metabolism to those of
      sham-ovx animals, there was little increase in bone volume. Interestingly,
      exogenous E2 caused a greater increase in cancellous bone volume than ovarian
      transplantation but also caused more marked suppression of bone formation, as
      assessed at the end of the study. In conclusion, exogenous E2 and ovarian
      transplantation exerted distinct effects on skeletal metabolism in osteopenic ovx
      rats, although the basis for this difference is currently unclear.

PMID- 7581971
TI  - Anti-prolactin autoantibodies and hyperprolactinaemia.

PMID- 7581975
TI  - Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin
      secretion and intracellular calcium concentration in rat pituitary.
AB  - Amiodarone (AM) and its major metabolite desethylamiodarone (DEA) are
      structurally similar to biologically active thyroid hormones. Amiodarone therapy
      is frequently associated with impairment of thyrotropic function, whose
      mechanisms are still controversial. Besides its effect on nuclear thyroid hormone
      binding. AM is able to displace dihydropyridine (DH) binding on membrane
      preparations from several tissues. By perifusing rat pituitary fragments and
      measuring thyrotropin (TSH) release we examined: the effect of AM on Ca(2+)
      dependent and DHP-sensitive potentiation of the TSH response to thyrotropin
      releasing hormone (TRH) induced by either triiodothyronine (T3, perifused for
      only 30 min before a TRH pulse) or by the prepro-TRH peptide 160-169 (PS4); and
      the effect of DEA on TRH-induced TSH response in the presence or absence of the
      DHP nifedipine. We show that AM reverses T3 or PS4 potentiation of the TSH
      response to TRH; this effect is specific because AM does not modify ionomycin
      potentiation of that response. In contrast, DEA significantly potentiates the TSH
      response to TRH and the DHP nifedipine reverses that potentiation. We also tested
      whether AM would change the acute T3-induced increase in intracellular Ca2+
      concentration by measuring intracellular Ca2+ ([Ca2+])i with fura-2 imaging on
      primary cultures of pituitary cells. We show that AM reverses the effect of T3 on
      [Ca2+]i as well as the PS4-induced increase in [Ca2+]i. In contrast, DEA
      increases [Ca2+]i and nifedipine reverses this effect. Our results suggest that
      AM and DEA display DHP-like effects on TRH-induced TSH release, behaving either
      as a Ca2+ channel blocker (AM) or as a Ca2+ channel agonist (DEA).

PMID- 7581977
TI  - Cigarette smoking and the thyroid.

PMID- 7581976
TI  - Ascorbate depletion prevents aldosterone stimulation by sodium deficiency in the
      guinea pig.
AB  - The concentration of ascorbic acid (vitamin C) in the adrenal cortex is higher
      than in any other organ. The role of vitamin C in the adrenal cortex is unknown,
      but data obtained with bovine adrenocortical cells in vitro favour its role as an
      antioxidant that especially protects aldosterone synthesis from damaging lipid
      peroxides. Alternatively, vitamin C could act as part of an auxiliary electron
      transport system for the last step of aldosterone synthesis. The effects of
      vitamin C depletion on adrenocortical function cannot be studied in the human for
      ethical reasons, so we subjected different groups of guinea pigs to vitamin C
      depletion, sodium depletion and combined vitamin C and sodium depletion. Other
      groups of animals on normal or vitamin C-deficient diets received high-dose
      adrenocorticotrophin (ACTH) injections for 3 days before sacrifice. Fifteen days
      of a vitamin C-free diet led to very low vitamin C levels in adrenals, liver and
      plasma without clear signs of scurvy. At this time, plasma aldosterone and
      aldosterone secretion by isolated adrenal cells were stimulated significantly by
      sodium deficiency. Simultaneous vitamin C depletion completely abolished the rise
      in aldosterone in vivo and in vitro, significantly reduced the conversion of
      [3H]deoxycorticosterone to [3H]aldosterone and impaired renal sodium
      conservation. Plasma renin activity (PRA), plasma ACTH and serum potassium were
      not different in the sodium-depleted and sodium plus vitamin C-depleted groups.
      Sodium depletion did not affect cortisol. Vitamin C depletion led to a
      significant increase in plasma cortisol without an increase in ACTH, while in
      vitro secretion of cortisol was slightly decreased.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7581978
TI  - Molecular defects in thyroid carcinomas: role of the RET oncogene in thyroid
      neoplastic transformation.
AB  - Tumors are believed to arise as a result of an accumulation of mutations in
      critical genes involved in the control of cell proliferation. Thyroid neoplasms
      represent a good model for studying the role of these mutations in epithelial
      cell multistep carcinogenesis because they comprise a broad spectrum of lesions
      with different degrees of malignancy. Recent reports have described the
      involvement of specific genetic alterations in different types of thyroid
      neoplasms. Papillary carcinomas are characterized by the activation of the
      receptor tyrosine kinases RET and TRK-A proto-oncogenes. Ras point mutations are
      frequently observed in tumors with follicular histology and a high prevalence of
      p53 point mutations have been found in anaplastic carcinomas. A definition of
      molecular defects characterizing thyroid tumors will be helpful in establishing
      sensitive and specific detection strategies and, in addition, to define genetic
      and environmental factors important for their pathogenesis.

PMID- 7581979
TI  - Renin secretion: the difficulty of extrapolating from in vitro to in vivo
      studies.

PMID- 7581981
TI  - Plasma neurotensin levels in humans: relation to hormone levels in diseases
      involving the hypothalamo-pituitary-thyroid axis.
AB  - This study was aimed to investigate, in humans, the possible relationship between
      plasma neurotensin (NT) levels and the activity of the hypothalamo-pituitary
      thyroid axis. Neurotensin was measured by radioimmunoassay in 14 healthy adult
      volunteers and in 41 patients among whom 10 were considered as controls and 31
      had thyroid dysfunction according to free thyroxine and thyrotropin plasma
      values. Basal NT levels were not significantly different in healthy adults and in
      control patients: 9.7 +/- 1.1 fmol/ml (mean +/- SEM) vs 13.3 +/- 2.9 fmol/ml,
      respectively. In patients with central hypothyroidism the NT level was
      significantly lower (5.7 +/- 1.2 vs healthy volunteers and controls; p < 0.05)
      and in patients with peripheral hypothyroidism and hyperthyroidism the NT level
      was significantly higher (35.9 +/- 12.8 and 29.9 +/- 9.5 fmol/ml, respectively,
      vs healthy adults (p < 0.01) and vs controls (p < 0.05)). After thyrotropin
      releasing hormone (TRH) injection (250 micrograms iv) in nine subjects (two
      control patients, five patients with hypothyroidism and two patients with
      hyperthyroidism), NT levels decreased independently of the endocrine status from
      mean values of 13.4 +/- 8.4 at basal level to 7.3 +/- 0.8 fmol/ml 30 min after
      injection (p < 0.01 on paired percentage decrease values). These data suggest
      that plasma NT levels in humans depend upon the pituitary-thyroid status and
      indicate that TRH could exert a negative regulation on circulating NT levels.

PMID- 7581980
TI  - Changes in prostaglandin synthesis and metabolism associated with labour, and the
      influence of dexamethasone, RU 486 and progesterone.
AB  - The objective was to compare the changes in prostaglandin synthesis and
      metabolism occurring within the fetal membranes that are associated with the
      onset of parturition and to study the effect of steroid hormones on prostaglandin
      metabolism. A tissue explant study was made of discs of amnion and chorion
      obtained from 24 pregnant women at 37-42 weeks' gestation following spontaneous
      labour and delivery (12 women) and elective caesarean section (12 women).
      Significantly more prostaglandin E2 (PGE2) and PGF2 alpha were synthesized by
      amnion obtained following spontaneous labour than elective caesarean section.
      Arachidonic acid stimulated both PGE2 and PGF2 alpha synthesis by amnion in both
      groups. Phorbol myristoyl acetate stimulated PGE2 synthesis in both groups. There
      was no difference between the groups in the capacity of the chorion to metabolize
      prostaglandins. Mifepristone (RU 486) reduced the metabolism of added PGE2
      following spontaneous labour, while dexamethasone and progesterone had no effect
      on prostaglandin metabolism. In conclusion, the increase in concentration of PGE2
      and PGF2 alpha associated with the onset of spontaneous labour is the result of
      an increase in synthesis rather than a reduction in metabolism. There was no
      decrease in metabolism to account for the increase in prostaglandin
      concentrations and, with the exception of mifepristone, metabolism was not
      altered by the addition of steroid hormones.

PMID- 7581982
TI  - Review of Turkish patients with growth hormone insensitivity (Laron type).
AB  - Clinical spectrum and endocrine details of thirteen Turkish children (age 0.3
      14.2 years; eight females and five males; ten prepubertal, three pubertal) with
      growth hormone insensitivity are presented. All patients display phenotypical
      features of severe growth hormone deficiency. The diagnosis based on height
      standard deviation score (SDS), basal growth hormone (GH), basal insulin-like
      growth factor I (IGF-I, IGF-I response in an IGF generation test and growth
      hormone binding protein (GHBP) measurements. The median height SDS was -7.4
      (range -3.2 to -10), weight for height index was 100 (range 81-152) and bone
      age/height age ratio was 2 (range 1.6-3.3). Endocrine investigations showed a
      median basal GH concentration of 61.4 mU/l (range 23.5-120 mU/l). Basal IGF-I
      level was below 10 ng/ml in all patients except one. None of the patients showed
      a significant IGF-I response to injections of GH (0.1 U/kg body weight for 4
      days). The median IGFBP-3 level was 0.23 mg/l (range 0.1-0.56 mg/l). The GHBP
      level was undetectable in all of 10 patients. The high number of patients in our
      center may be due to the high rate of consanguinity among the Turkish population
      and the referral facility of our center in the area. These patients may benefit
      from the new therapy with recombinant human IGF-I.

PMID- 7581983
TI  - Peptide-containing nerve fibres in normal human parathyroid glands and in human
      parathyroid adenomas.
AB  - There are only a few studies on the innervation of the human parathyroid glands
      and the content of neurotransmitters. We therefore studied the occurrence and
      distribution of peptide-containing and adrenergic nerve fibres and the
      coexistence pattern of neuromessengers by immunocytochemistry in normal
      (unaffected) and adenomatous parathyroid glands from patients undergoing surgery
      for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich
      supply of nerve fibres and terminals containing two general neuronal markers,
      protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and
      tyrosine hydroxylase (TH). They were seen close to blood vessels and,
      occasionally, among the endocrine cells. Only a few nerves contained calcitonin
      gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P
      (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general
      density of innervation, using PGP 9.5 and synaptophysin as markers, varied
      greatly among the different adenomas examined. This applied also to the density
      of fibres and terminals containing specific types of messengers. Some of the
      tumours had a rich supply of TH- and NPY-containing nerve fibres, while others
      contained only few scattered fibres. The CGRP-containing fibres varied from
      moderate in number to no detectable fibres. The PACAP-, SP- and VIP-containing
      fibres were always very few or not detectable. It is not inconceivable that the
      wide variation in general density of the innervation and frequency of peptide
      containing nerves among individual parathyroid adenomas is of significance for
      their hormone secretory behaviour.

PMID- 7581984
TI  - Selective increases in adrenal steroidogenic capacity during acute respiratory
      disease in infants.
AB  - To examine steroidogenic responses of the different zones of the adrenal cortex
      to acute disease we determined the basal and adrenocorticotropin (ACTH)
      stimulated levels of cortisol, dehydroepiandrosterone (DHEAS) and aldosterone in
      16 infants aged 1-4 months with acute bronchiolitis. Fourteen of the infants were
      retested after recovery. During illness the mean basal levels of cortisol and
      DHEAS were twice as high as the levels after recovery (370 vs 180 nmol/l and 2.7
      vs 1.3 mumol/l, respectively). The mean peak ACTH-stimulated levels of cortisol
      and DHEAS during illness were 1.5- and 2.5-fold higher, respectively, than the
      levels found after recovery. Although aldosterone secretion was stimulated > or =
      3-fold by ACTH, illness was not associated with any change in aldosterone
      secretory capacity. The basal and stimulated levels of both cortisol and DHEAS
      during illness and after recovery were correlated significantly. Thus, the
      relative steroidogenic capacities for these two steroids were characteristic of
      the individual infant and showed constancy over a period of at least several
      weeks. While the levels of cortisol and aldosterone were not dependent on the age
      of the infants, both the basal and stimulated levels of DHEAS correlated strongly
      with age. We conclude that during acute disease the steroidogenic capacity
      selectively increases in the zones that secrete cortisol and DHEAS (only in
      infants < 3 months) but not in the zona glomerulosa that secretes aldosterone.
      The DHEAS response may be related to its putative effects to enhance immune
      responses.

PMID- 7581985
TI  - Collagen metabolism in two types of autosomal dominant osteopetrosis during
      stimulation with thyroid hormones.
AB  - In order to investigate collagen metabolism in two different types of autosomal
      dominant osteopetrosis (ADO), eight patients with type I (aged 23-61 years, mean
      40.4 years) and nine patients with type II ADO (aged 20-49 years, mean 32.8
      years) were compared with ten normal controls (aged 22-54 years, mean 35.4
      years). The subjects were treated with 100 micrograms of triiodothyronine (T3)
      daily for 7 days and followed for a total of 4 weeks. Serum T3 increased in all
      subjects and a corresponding suppression of thyroid-stimulating hormone (TSH) was
      observed. Serum carboxy-terminal propeptide of type I collagen (S-PICP) in the
      control and type I groups showed no difference at baseline, whereas type II was
      lower than controls (p < 0.01). No significant alterations following stimulation
      were observed in any of the groups. Serum BGP (osteocalcin) values in the two
      patient groups were insignificantly lower than controls both at baseline and
      throughout the study. Following stimulation, a significant response was seen in
      the three groups (p < 0.001). The increases during the treatment period (delta
      values) for controls, type I and type II were 47.6% (p < 0.01), 51.7% (p = 0.05)
      and 34.8% (NS), respectively, with no difference between the groups. Serum bone
      specific alkaline phosphatase (S-ALP) was not different between the groups and no
      alterations were observed in relation to treatment. The serum N-terminal
      propeptide of type III collagen (S-PIIINP) showed no difference at baseline
      between type I and controls but was significantly higher (p < 0.003) in type II
      than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581986
TI  - Transmission of thyrotoxicosis of autoimmune type by sibling allogeneic bone
      marrow transplant.
AB  - This case report is on a 25-year-old male with acute myeloblastic leukaemia who
      achieved a remission after cytoxic therapy and whole-body irradiation. He
      received a bone marrow transplant from his human leucocyte antigen (HLA)
      identical sister who had unsuspected autoimmune thyroid disease. Nine months
      later the bone marrow recipient developed thyrotoxicosis of autoimmune type at a
      time when his circulating lymphocytes were of 46XX karyotype. It is suspected
      that the thyrotoxicosis resulted from the transplantation of a clone of
      lymphocytes predisposed to the production of thyroid-stimulating autoantibodies.

PMID- 7581987
TI  - Interactions between angiotensin II and norepinephrine on renin release by
      juxtaglomerular cells.
AB  - While the interactions between angiotensin II (Ang II) and norepinephrine (NE) on
      cardiovascular responses are well known, their effects on renin responses are
      not. We determined the renin secretion rate (RSR) and intracellular calcium level
      in juxtaglomerular cells harvested from Sprague-Dawley rats using a
      radioimmunoassay and a two-dimensional calcium analyzer. The effect of Ang II and
      NE was inhibitory on RSR and stimulatory on intracellular calcium. The NE-induced
      RSR response was amplified in the presence of Ang II (20 nmol/l). The NE-induced
      intracellular calcium response was also potentiated by the Ang II. There was a
      significant correlation (r = 0.994, p < 0.0001) between the changes in the RSR
      and those in intracellular calcium levels. Losartan (0.1 mumol/l). an Ang II type
      1 receptor antagonist, blocked the Ang II threshold RSR responses and completely
      abolished the Ang II-related enhancements. The exclusion of calcium from the
      buffer reduced the maximal RSR response to NE but did not prevent the
      enhancement, suggesting the importance of the mobilization of intracellular
      calcium in the mechanism. The Ang II-induced RSR was amplified in the presence of
      NE (0.2 mumol/l). The Ang II-induced intracellular calcium response was also
      potentiated by the NE. A significant correlation (r = 0.996, p < 0.0001) between
      the changes in the RSR and the changes in intracellular calcium levels was also
      noted. Prazosin (1 mumol/l), an alpha 1-adrenoceptor antagonist, blocked the NE
      threshold RSR responses and abolished the agonist-related enhancements. The
      calcium-free buffer diminished this amplication with a slight decrease in the
      maximum RSR response to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581989
TI  - Hypothalamic multiunit activity and pulsatile luteinizing hormone release in the
      castrated male rat.
AB  - Using chronically implanted microelectrodes, multiunit electrical activity (MUA)
      was recorded from the arcuate nucleus of freely moving gonadectomized male rats.
      Intermittent increases in MUA activity (MUA volleys) closely associated with
      luteinizing hormone pulses measured in the peripheral circulation were observed,
      which confirms that this experimental approach can be used for monitoring the
      activity of the gonadotropin-releasing hormone-associated hypothalamic pulse
      generator in the male rat. The mean MUA volley frequency was 22.2 min (range 13
      38 min), whereas the mean MUA volley duration was 2.7 +/- 0.8 min (standard
      deviation). In addition to a large inter-individual variability. MUA volley
      intervals also showed an important intra-individual variability. This observation
      suggests that, beside the mean frequency of pulse generator activation, the
      degree of variability in gonadotropin-releasing hormone-associated pulse
      generator activity might be an additional relevant parameter in the
      characterization of the reproductive function in the male rat.

PMID- 7581988
TI  - Inhibition of aldosterone turn-off phenomenon following chronic
      adrenocorticotropin treatment with in vivo administration of antiglucocorticoid
      and antioxidants in rats.
AB  - Chronic adrenocorticotropin (ACTH) treatment in rats leads to a fall in
      aldosterone secretion (aldosterone turn-off or "aldosterone escape" phenomenon)
      with a concomitant rise in corticosterone. To elucidate whether ACTH-induced
      aldosterone suppression is mediated by steroid type II receptor or related to a
      free-radical effect by over-synthesized corticosterone, we examined the effects
      of a glucocorticoid antagonist, RU486, and antioxidants dimethyl sulfoxide (DMSO)
      and vitamin E, on the aldosterone turn-off phenomenon in rats. Each rat received
      daily for 5 days a different dose of ACTH-Z (5, 10, 20 or 40 micrograms/100 g
      body weight) 1 mg RU486/100 g body weight, 100 microliters (1.3 mmol) DMSO/100 g
      body weight or 2 mg vitamin E/100 g body weight with subcutaneous injection.
      Plasma steroid levels and in vitro release of steroids from the adrenal capsule
      were measured. The ACTH-Z treatment caused a dose-dependent increase in
      corticosterone and a decrease in aldosterone in both plasma and adrenal capsule
      experiments, as well as an increase in adrenal weights. For the following study 5
      micrograms/100 g body weight of ACTH-Z was used. Administration of RU486 alone
      caused no change in plasma aldosterone level compared to controls, even though
      the steroid type II receptor was blocked, as evidenced by significant increases
      in plasma ACTH and corticosterone levels. Concomitant administration of RU486 and
      ACTH-Z increased both plasma corticosterone and aldosterone levels (p < 0.01) but
      decreased adrenal capsule corticosterone production (p < 0.05) compared to the
      rats treated with ACTH-Z alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7581990
TI  - Identification and characterization of a corticotrophin-releasing hormone
      receptor in human placenta.
AB  - Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal
      placental circulation and has paracrine actions in placental tissue, suggesting
      that CRH receptors may be present in the human placenta. We have now identified
      and characterized placental CRH binding sites and compared them to those
      described previously in human myometrium and rat pituitary. Radiolabelled ovine
      CRH binding to placental membranes was pH-, time-, temperature- and divalent
      cation-dependent and was reversible in the presence of 1 mumol/l unlabelled ovine
      CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean
      section revealed dissociation constants (Kd) of 214.5 +/- 84 pmol/l (N = 8) and
      45.4 +/- 23.9 pmol/l (N = 9), respectively. The Kd for caesarean placental
      binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and
      rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered
      placentae the CRH binding sites had a much lower affinity (p < 0.05). The
      receptor densities (Bmax) of vaginally delivered and caesarean-delivered
      placentae were 28.6 +/- 9.6 and 6.1 +/- 2.8 fmol/mg, respectively (p < 0.05).
      Chemical cross-linking studies using disuccinimidyl suberate indicated that the
      molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD.
      We conclude that there is a high-affinity population of CRH binding sites in the
      human placenta that are physicochemically similar to pituitary and myometrial CRH
      receptors. The CRH receptor properties in the placenta change in response to
      labour, when CRH levels in maternal blood are highest, suggesting that placental
      CRH may regulate its receptor.

PMID- 7581992
TI  - Endothelin-induced phosphoinositide hydrolysis in the muscular layer of stem
      villi vessels of human term placenta.
AB  - In the present study, we examined the relationship between endothelin receptors
      and phosphoinositide breakdown in muscle explants of placental stem villi
      vessels. All peptides examined, i.e. endothelin-1 (ET-1), ET-3, sarafotoxin 6b
      (S6b) and S6c, were able to induce phosphoinositide hydrolysis in a dose
      dependent manner: ET-1 was more potent than S6b and ET-3, with corresponding EC50
      values of 44 +/- 16 pmol/l, 18 +/- 13 nmol/l and 33 +/- 24 nmol/l, respectively.
      Sarafotoxin induced only moderate stimulation of inositol phosphate accumulation.
      Both ET-1- and S6b-induced accumulation of inositol phosphate was almost totally
      (90%) inhibited by 100 mumol/l BQ 123, while the S6c response was not affected by
      the ETA receptor antagonist. In contrast, the ETB receptor antagonist IRL 1038
      inhibited S6c-induced inositol phosphate accumulation by more than 80%, whereas
      inhibition was only about 30% for ET-1 and S6b stimulations. This indicates that
      both ETA and ETB receptors were coupled to the phospholipase C transducing system
      in the muscular layer of placental stem villi vessels, and there is evidence that
      the phosphoinositide hydrolysis response is obtained predominantly via ETA
      receptor activation.

PMID- 7581993
TI  - Usefulness of recombinant human prolactin for treatment of poor puerperal
      lactation in a rat model.
AB  - Recombinant human prolactin (r-hPRL) was produced by a line of murine C127 cells
      transfected with human PRL gene. To assess the biological efficacy of r-hPRL in
      vivo, we studied its influence on milk secretion using a rat model in which
      lactation was reduced by bromocriptine treatment. Puerperal rats were injected
      daily for 9 days after delivery with bromocriptine or bromocriptine plus r-hPRL,
      and lactational performance was assessed by weighing the pups. The concentrations
      of rat and human PRL in rat serum were measured by specific radioimmunoassays and
      the mammary glands were examined on postpartum day 10. Daily injection of
      bromocriptine (0.1 mg/rat) significantly reduced the endogenous level of rat PRL
      and impaired the weight gain of the pups. Administration of r-hPRL increased the
      serum level of human PRL. Daily injections of r-hPRL (50 micrograms/rat, twice a
      day) restored lactational performance and significantly increased the weight of
      the pups. The detrimental effect of bromocriptine on the mammary glands, assessed
      by both weight and histological appearance, was reversed by administration of r
      hPRL. These results demonstrate that r-hPRL is biologically active in vivo and
      replacement therapy of r-hPRL is effective in improving the lactational
      performance in bromocriptine-treated rats, and also that r-hPRL may be useful for
      the treatment of women with poor lactation.

PMID- 7581991
TI  - Evidence for oestrogenic regulation of heat shock protein expression in human
      endometrium and steroid-responsive cell lines.
AB  - Gene amplification with target-specific primers (reverse-transcription polymerase
      chain reaction (RT-PCR)) was used to monitor the relative expression of oestrogen
      and progesterone receptor mRNAs alongside the mRNAs for heat shock proteins HSP
      90 alpha, HSP 90 beta and HSP 70a in normal samples of human endometrial tissue
      over the whole menstrual cycle and in short-term cultures of steroid-responsive
      (T47-D) and unresponsive (HRT-18) cell lines exposed to oestradiol and
      progesterone over a 24-h incubation period. In endometrium, oestrogen and
      progesterone receptors followed the expected patterns of expression at the
      protein level during the menstrual cycle and also showed a positive correlation
      of expression with each other throughout (r = 0.514). Of the HSPs only HSP 90
      alpha expression correlated positively with oestrogen receptor (r = 0.687), while
      HSP 70a expression, which peaked in the late secretory stage, displayed a
      significantly inverse correlation with HSP 90 beta expression (r = -0.526). All p
      values < 0.05. In T47-D cell cultures, oestrogen receptor expression was
      stimulated transiently by oestradiol (10(-7) mol/l) and more persistently by
      progesterone (10(-7) mol/l). Progesterone receptor expression was depressed by
      progesterone and weakly stimulated by oestradiol. HSP 70a and HSP 90 alpha
      expression were stimulated by oestradiol. Progesterone generally depressed HSP 90
      alpha expression and simultaneous addition of both oestradiol and progesterone to
      the culture medium was antagonistic to HSP 90 alpha expression. No clear effect
      of agonist addition on HSP mRNA expression was apparent in the HRT-18 cultures. A
      possible mechanism for observed oestrogenic effects on HSP expression is put
      forward.

PMID- 7581996
TI  - Plasmodium development in the myxomycete Physarum polycephalum: genetic control
      and cellular events.

PMID- 7581997
TI  - Pilus biogenesis gene, pilC, of Neisseria gonorrhoeae: pilC1 and pilC2 are each
      part of a larger duplication of the gonococcal genome and share upstream and
      downstream homologous sequences with opa and pil loci.
AB  - Pili of Neisseria gonorrhoeae mediate attachment of the bacteria to target cells
      and undergo both phase and antigenic variation. PilC is a 110 kDa minor pilus
      associated protein involved in pilus biogenesis and attachment. The expression of
      PilC is turned on and off at high frequency and is controlled by frameshift
      mutations in a run of G residues positioned in the region encoding the signal
      peptide. Most strains of N. gonorrhoeae carry two copies of pilC. The DNA
      sequence of pilC1 of strain MS11 is presented and compared to the sequence of the
      3' end of pilC2. These two genes are highly homologous, but not identical. The
      putative transcriptional terminator of pilC1 contains a pair of inverted uptake
      sequences for gonococcal DNA (5'-GCCGTCTGAA-3'). An 88 bp sequence located
      upstream of the pilC1 gene has also been reported to precede several opa genes of
      N. gonorrhoeae. Shorter regions positioned both downstream and upstream of pilC1
      can also be found in silent pil loci as well as close to opa genes. The pilC
      genes are part of a duplication of a larger DNA region extending more than 2 kb
      downstream of the coding region.

PMID- 7581994
TI  - Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with
      calcitriol--effects of 22-oxacalcitriol on osteoclast-like cell formation and
      bone-resorbing activity.
AB  - 22-Oxacalcitriol (OCT), a synthetic vitamin D3 analog, can mimic the ability of
      calcitriol to differentiate leukemia and skin cells, to enhance the immune
      response and to suppress parathyroid hormone secretion, but has much less
      calcemic activity than that of calcitriol. The mechanism of this selective action
      remains not fully understood, and the actions of OCT on bone metabolism are
      little known. The present study was, therefore, designed to investigate the
      effects of OCT and calcitriol on: the proliferation and functions of osteoblastic
      MC3T3-E1 cells; osteoclast-like cell formation from hemopoietic blast cells in
      the absence of stromal cells as well as from unfractionated bone cells in the
      presence of stromal cells; bone resorption; and the proliferation of MC3T3-E1
      cells via monocytes. 22-Oxacalcitriol and calcitriol inhibited [3H]thymidine
      (TdR) incorporation, alkaline phosphatase activity and collagen synthesis of
      MC3T3-E1 cells to a similar degree. Both OCT (10(-10)-10(-8) mol/l) and
      calcitriol significantly and similarly stimulated osteoclast-like cell formation
      from both hemopoietic blast cells and unfractionated bone cells. 22-Oxacalcitriol
      (10(-10) and 10(-8) mol/l) significantly stimulated bone resorption, although to
      a slightly lesser degree than did calcitriol. Human monocyte-conditioned medium
      (CM) significantly stimulated TdR incorporation into MC3T3-E1 cells. On the other
      hand, CM obtained from monocytes treated with calcitriol (10(-10)-10(-8) mol/l)
      significantly inhibited TdR incorporation in a dose-related fashion, whereas CM
      obtained from monocytes treated with OCT (10(-10)-10(-8) mol/l) significantly
      stimulated TdR incorporation in a dose-related fashion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7581999
TI  - Glucosaminidase of Bacillus subtilis: cloning, regulation, primary structure and
      biochemical characterization.
AB  - The 90 kDa glucosaminidase protein was purified to apparent homogeneity from
      vegetative cells of Bacillus subtilis AC327, and then the corresponding gene was
      cloned into Escherichia coli in two inactive forms by standard procedures.
      Nucleotide sequencing of the glucosaminidase region revealed a monocistronic
      operon, (designated lytD = cwIG) encoding a 95.6 kDa protein, comprising 880
      amino acid residues, which has a typical signal peptide. Moreover, another
      monocistronic operon (designated pmi = orfX), encoding a 35.4 kDa protein, was
      found upstream of the glucosaminidase gene. Expression of a lytD-lacZ fusion
      gene, driven by lytD regulatory sequences, was observed during the exponential
      growth phase. The introduction of a sigD null mutation greatly reduced (by about
      95%) the expression of the fusion. Amino acid sequence analysis of the
      glucosaminidase showed two types of direct repeats, each type being present
      twice, in the N-terminal-to-central region of the glucosaminidase: these repeats
      probably represent the cell-wall-binding domain. Zymographic analysis revealed
      that the 90 kDa glucosaminidase is partly processed to several smaller proteins
      (35-39 kDa), retaining lytic activity. Processing of these proteins occurred
      between the N-terminal cell-wall-binding and C-terminal catalytic domains of the
      glucosaminidase, the site being located between the 569th and 606th codons of the
      glucosaminidase. Serial deletions from the N-terminus of the glucosaminidase
      revealed that the loss of more than one repeating unit drastically reduces its
      lytic activity toward cell walls. The lytD gene product, in either an intact or a
      truncated form, was found to be lethal for E. coli, and the N-terminally
      truncated glucosaminidase proteins, produced in E. coli, were very unstable. The
      partially purified glucosaminidase from B. subtilis was found to be very unstable
      at low ionic strength at 37 degrees C, but this instability was overcome by the
      addition of either SDS-purified cell wall or protease inhibitor (PMSF) to the
      enzyme or after purification of the glucosaminidase to apparent homogeneity.

PMID- 7581998
TI  - In Bacillus subtilis 168, teichoic acid of the cross-wall may be different from
      that of the cylinder: a hypothesis based on transcription analysis of tag genes.
AB  - Five of the genes known to encode the enzymes for the synthesis of poly(glycerol
      phosphate), the major teichoic acid of Bacillus subtilis 168, are organized in
      two divergently transcribed operons, tagAB and tagDEF. lacZ and gus
      transcriptional fusions to the first genes of these operons revealed that: (i) in
      media of different richness, higher growth rates were paralleled by lower
      transcription levels; (ii) upon transition to stationary phase, the transcription
      per unit mass of both operons increased abruptly by a factor of about two; and
      (iii) a rise in temperature was accompanied by decreased transcription of tagA
      and increased transcription of tagD. Mapping of transcription start points
      revealed two divergent sigma A-controlled promoters. Although tagD and the
      neighbouring downstream gene tagE are transcribed from the same promoter, the
      latter was expressed at a much lower level than the former. Moreover, expression
      of tagE, and of the translationally coupled tagF, did not increase at the onset
      of the stationary phase, indicating that additional regulatory signals may act in
      the intergenic tagD-tagE region. Optimal transcription of these operons appears
      to require the entire regulatory region, suggesting that tag gene expression may,
      among other factors, be regulated by the three-dimensional configuration of this
      segment. The biological implications of these results are discussed.

PMID- 7581995
TI  - Quantity of Na/K-ATPase and glucose transporters in the plasma membrane of rat
      adipocytes is reduced by in vivo triiodothyronine.
AB  - The expression of sodium-potassium pumps and glucose transporters in pure
      adipocyte plasma membranes from a hyperthyroid animal model was studied.
      Hyperthyroidism was induced by enteral administration of five doses of 90
      micrograms of triiodothyronine every second day to 8-week-old rats. Following
      isolation of epididymal adipocytes, 3-O-methylglucose transport was measured and
      the number of Na/K-ATPase-(alpha 1- and alpha 2-isoforms) and glucose transporter
      (GLUT1 and GLUT4) molecules in sheets of adipocyte plasma membrane were
      determined by quantitative immunoelectron microscopy, using gold labelling.
      Maximal in vitro insulin stimulation of adipocytes increased the glucose
      transport rate and the amount of GLUT4 in the plasma membrane 15-fold, whereas
      the amount of alpha 2 was unaffected. In adipocytes from hyperthyroid rats, mean
      adipocyte volume was decreased by 18% and the quantities of GLUT4 per unit area
      of plasma membrane (maximal insulin stimulation) and of alpha 2 were decreased by
      19% and 15%, respectively. Thus, hypotrophia of fat tissue in the hyperthyroid
      state is associated with a decreased expression in the plasma membrane of the
      glucose transporter GLUT4 and the alpha 2-isoform of Na/K-ATPase.

PMID- 7582001
TI  - Physical and genetic map of the genome of Campylobacter upsaliensis.
AB  - A physical map of Campylobacter upsaliensis ATCC 43954 was constructed from DNA
      fragments generated by SalI (5' G/TCGAC), NarI (5' GG/CGCC) and BssHII (5'
      G/CGCGC) restriction digests separated using pulsed-field gel electrophoresis.
      The size of the C. upsaliensis genome was approximately 2000 kb, providing
      evidence of the largest Campylobacter genome sized to date. Twenty-one fragments
      created from these restriction digests were assembled into a physical map using a
      combination of complementary methods including cross-Southern hybridization,
      hybridization fingerprint analysis and hybridization with homologous and
      heterologous (from Campylobacter jejuni) gene probes. The position of ten genetic
      loci, including that of the iron-uptake regulatory (fur) gene, were localized to
      the physical map. A genomic library of C. upsaliensis ATCC 43954 was constructed
      in lambda Gem-11 vector. Fifty thousand recombinants with an average size of 16
      kb represent a library about 200 times the size of the genome. Using C. jejuni
      DNA probes, clones representing C. upsaliensis flaA, fur and ftsZ genes were
      isolated and localized to the physical map.

PMID- 7582002
TI  - Study of the organization of the genomes of Escherichia coli, Brucella melitensis
      and Agrobacterium tumefaciens by insertion of a unique restriction site.
AB  - Tn5Map, a Tn5 derivative containing the 18 bp I-SceI site, was delivered from a
      RP4-mobilizable, RK6-derived suicide vector to Escherichia coli HB101, Brucella
      melitensis and Agrobacterium tumefaciens C58, which all lack natural I-SceI sites
      in their genomes. Digestion of the DNA from Tn5Map-containing strains and
      analysis by pulsed-field gel electrophoresis (PFGE) revealed that these
      derivatives contained a single transposon insertion. These digests also gave
      direct and independent proof for the single circular chromosome of E. coli, and
      for the presence of two circular chromosomes in B. melitensis and of a circular
      and a linear chromosome in A. tumefaciens C58 (which also contains two large
      circular plasmids). This rapid and versatile technique is potentially applicable
      to the study of the genomic organization in all Gram-negative bacteria which
      support Tn5 transposition. Moreover, linearization of circular replicons could be
      the first step for a rapid method of physical mapping.

PMID- 7582000
TI  - Sequence, genetic analysis, and expression of Actinobacillus pleuropneumoniae
      transferrin receptor genes.
AB  - The tbpA and tbpB genes encoding the transferrin receptor proteins Tbp1 and Tbp2
      from a serotype 7 strain of Actinobacillus pleuropneumoniae were cloned,
      sequenced, and expressed in Escherichia coli. The tbpB gene was preceded by
      putative promoter and regulatory sequences and was separated from the downstream
      tbpA gene by a 13 bp intercistronic sequence suggesting that the two genes may be
      coordinately transcribed. Determination of the nucleotide sequence of this region
      facilitated PCR amplification of the tbp region from a serotype 1 strain for
      comparative purposes. The deduced amino acid sequences of the Tbp1 proteins had
      regions of homology with Neisseria Lbp and Tbp1s and with TonB-dependent outer
      membrane (OM) receptors of E. coli. The deduced amino acid sequences of the Tbp2
      proteins were nearly identical to those presented in previous studies. Upon high
      level expression of the tbpA gene, a large proportion of the recombinant Tbp1 was
      found in inclusion bodies and could not be affinity-isolated with immobilized
      porcine transferrin. Most of the remaining expressed Tbp1 was present in the OM
      fraction, was expressed at the surface of E. coli cells, and retained binding
      activity that was specific for the C-lobe of porcine transferrin. Although
      recombinant Tbp2 was found in inclusion bodies during high-level expression, a
      significant proportion was associated with a novel OM fraction that appeared in
      sucrose density gradients which was distinct from the OM fraction containing
      recombinant Tbp1. The recombinant Tbp2 was accessible at the surface yet was
      unable to bind porcine transferrin. In contrast to previous observations, the
      binding by recombinant Tbp2 was specific for the C-lobe of porcine transferrin.
      These results indicate that the A. pleuropneumoniae transferrin receptor proteins
      have similar properties to the receptor proteins in Neisseria spp. and
      Haemophilus influenzae, and that functional studies performed with recombinant
      receptor proteins need to consider differences in processing and export of these
      proteins when expressed in heterologous hosts.

PMID- 7582003
TI  - Phosphatase production and activity in Citrobacter freundii and a naturally
      occurring, heavy-metal-accumulating Citrobacter sp.
AB  - The ability of a naturally occurring Citrobacter sp. to accumulate cadmium has
      been attributed to cellular precipitation of CdHPO4, utilizing HPO4(2-) liberated
      via the activity of an overproduced, Cd-resistant acid-type phosphatase.
      Phosphatase production and heavy metal accumulation by batch cultures of this
      strain (N14) and a phosphatase-deficient mutant were compared with two reference
      strains of Citrobacter freundii. Only strain N14 expressed a high level of acid
      phosphatase and accumulated lanthanum and uranyl ion enzymically. Acid
      phosphatase is regulated via carbon-starvation; although the C. freundii strains
      overexpressed phosphatase activity in carbon-limiting continuous culture, this
      was approximately 20-fold less than the activity of strain N14 grown similarly.
      Citrobacter strain N14 was originally isolated from a metal-contaminated soil
      environment; phosphatase overproduction and metal accumulation were postulated as
      a detoxification mechanism. However, application of Cd-stress, and enrichment for
      Cd-resistant C. freundii ('training'), reduced the phosphatase activity of this
      organism by about 50% as compared to Cd-unstressed cultures. The acid phosphatase
      of C. freundii and Citrobacter N14 had a similar pattern of resistance to some
      diagnostic reagents. The enzyme of the latter is similar to the PhoN acid
      phosphatase of Salmonella typhimurium described by other workers; the results are
      discussed with respect to the known phosphatases of the enterobacteria.

PMID- 7582004
TI  - A NADP-glutamate dehydrogenase mutant of the petit-negative yeast Kluyveromyces
      lactis uses the glutamine synthetase-glutamate synthase pathway for glutamate
      biosynthesis.
AB  - The activities of the enzymes involved in ammonium assimilation and glutamate
      biosynthesis were determined in wild-type and NADP-glutamate dehydrogenase (GDH)
      null mutant strains of Kluyveromyces lactis. The specific NADP-GDH activity from
      K. lactis was fivefold lower than that found in Saccharomyces cerevisiae. The
      glutamine synthetase (GS) and glutamate synthase (GOGAT) activities were similar
      to those reported in S. cerevisiae. The NADP-GDH null mutant was obtained by
      transforming the uraA strain MD2/1 with a linearized integrative yeast vector
      harbouring a 390 bp fragment of the NADP-GDH structural gene. This mutant grew as
      well as the parent strain on ammonium, but showed GS and GOGAT activities higher
      that those found in the wild-type strain, implying that the GS-GOGAT pathway
      could play a leading role in glutamate biosynthesis in K. lactis. Southern
      blotting analysis of K. lactis chromosomes separated by contour-clamped
      homogeneous electric field electrophoresis, indicated that the NADP-GDH
      structural gene is localized on chromosome VI.

PMID- 7582005
TI  - Induction and repression of alpha-amylase production in batch and continuous
      cultures of Aspergillus oryzae.
AB  - The intra- and extracellular concentrations of alpha-amylase in Aspergillus
      oryzae have been measured during batch culture of a wild-type strain and two
      recombinant strains. The mean intracellular level for the two recombinant strains
      was about four to five times the level of the wild-type strain. The recombinant
      strains also had a higher alpha-amylase productivity, whereas the residence time
      of the intracellular alpha-amylase pool was approximately the same for the three
      strains. At high glucose concentrations there was a low constitutive synthesis of
      alpha-amylase, whereas at low glucose concentrations derepression resulted in an
      increased production rate. Shifts from a glucose- to a maltose-limited chemostat
      showed that maltose induces both the production and secretion of alpha-amylase.
      Finally, from immunoblots, both a glycosylated and an unglycosylated alpha
      amylase have been detected.

PMID- 7582006
TI  - Analysis of lysine-dependent yeast sporulation: a decrease in cyclic AMP is not
      required for initiation of meiosis and sporulation in Saccharomyces cerevisiae.
AB  - Cells of the yeast Saccharomyces cerevisiae sporulated in nutrient-rich medium
      containing L-lysine. Sporulation was specific to the presence of L-lysine and was
      initiated when the cellular content of this basic amino acid reached
      approximately 0.2-0.5 mmol (g cells)-1, at early stationary phase. The formation
      of asci was most efficient at pH 7.0 and 50-100 mM L-lysine; in these optimum
      conditions, the sporulation frequency reached about 60% after 5 d incubation. The
      L-lysine-dependent sporulation system in nutrient-rich conditions was distinct
      from the currently used potassium-acetate-dependent system in nutrient-deficient
      conditions. Analysis of the L-lysine-dependent system indicated that, prior to
      entrance into meiosis and/or sporulation processes, the yeast cells change in
      shape, their pool sizes for L-cysteine and glutathione alter, and they synthesize
      a protein with a molecular mass of 15 kDa. A low level of cAMP was not required
      for the entrance into meiosis and/or sporulation.

PMID- 7582009
TI  - Sequence and functional analysis of the Streptomyces phaeochromogenes plasmid
      pJV1 reveals a modular organization of Streptomyces plasmids that replicate by
      rolling circle.
AB  - pJV1 is an 11 kb, high-copy-number conjugative Streptomyces phaeochromogenes
      plasmid that replicates by the rolling circle mechanism (RCR). Sequencing
      combined with functional analysis of deletion, insertion and frameshift mutations
      was used to characterize the genes involved in plasmid transfer and chromosome
      mobilization (Cma), the single-strand origin for RCR and an associated strong
      incompatibility (Sti) determinant. pJV1 contains two essential transfer genes
      whose expression is regulated by an adjacent repressor gene with similarity to
      the GntR family of regulators. A consensus sequence specific for the helix-turn
      helix motifs of repressor proteins of Streptomyces plasmids is proposed.
      Unregulated expression of the transfer genes by inactivation of the repressor is
      lethal. Three additional genes increase intramycelial plasmid spread resulting in
      pock formation but, unlike the essential transfer genes, are not required for
      Cma. The pJV1 transfer genes and their regulatory region, but not the minimal
      replication region encoding the double-strand replication origin and replication
      protein, are similar in their sequence and arrangement to those of the
      Streptomyces nigrifaciens plasmid pSN22, revealing a modular organization of
      Streptomyces RCR plasmids.

PMID- 7582007
TI  - Two heterocyst-specific DNA rearrangements of nif operons in Anabaena cylindrica
      and Nostoc sp. strain Mac.
AB  - Two site-specific DNA rearrangements occur during heterocyst differentiation in
      the cyanobacterium Anabaena sp. strain PCC 7120: the deletion of an 11 kb element
      from within the nifD gene and the deletion of a 55 kb element from within the
      fdxN gene. Three Nostoc and six Anabaena strains were screened for the presence
      of the nifD and fdxN elements by Southern hybridization with Anabaena PCC 7120
      DNA probes. Eight of the nine strains contained DNA sequences that were similar
      to the nifD element. Three strains, Nostoc sp. strain Mac, Anabaena cylindrica
      and Anabaena sp. strain M131, also showed significant similarity to portions of
      the 55 kb fdxN element. Anabaena sp. strain CA lacked both the nifD and fdxN
      elements. Southern analysis of vegetative cell and heterocyst DNA from A.
      cylindrica and a Fox+ revertant of Nostoc Mac (isolate R2) showed rearrangement
      of the nifD and fdxN elements in heterocysts. We found no RFLPs between Anabaena
      M131 and Anabaena PCC 7120 suggesting that strain M131 is a Het- derivative of
      strain PCC 7120.

PMID- 7582008
TI  - The CrP operon of Chlamydia psittaci and Chlamydia pneumoniae.
AB  - One of the critical developmental events during the unique intracellular life
      cycle of Chlamydiae is their differentiation from a metabolically active,
      replicative form or reticulate body (RB) to an infectious extracellular form of
      the organism (elementary body or EB). This process is characterized by the
      expression of two extraordinarily cysteine-rich envelope proteins of molecular
      masses 9 kDa and 60 kDa. We describe the molecular cloning and sequence
      determination of the 9 kDa cysteine-rich proteins (CrPs) of C. pneumoniae and C.
      psittaci. Comparison of these 9 kDa CrP amino acid sequences with those of C.
      trachomatis showed regions of structural variation and conservation.
      Transcription of the 9 kDa CrP genes occurred as both a monocistronic message and
      as a bicistronic message which included the 60 kDa CrP gene. Transcription of the
      9 kDa and 60 kDa CrP genes was tightly linked to the chlamydial growth cycle with
      synthesis of their mRNAs and consequent translation of the 60 kDa CrPs occurring
      as RBs differentiated to form EBs. The maximal rate of transcription occurred
      late in the growth cycle from a single but highly conserved promoter which had
      close similarity with the Escherichia coli consensus promoter sequences. A stem
      and loop structure which could be involved in regulating translation of mRNA
      occurred in all three species between the transcriptional start point and the
      ribosome binding site. Although transcription is initiated from a single promoter
      in all three chlamydial species, transcriptional termination points for the
      monocistronic and bicistronic mRNAs differ in both number and position.

PMID- 7582010
TI  - Depression of streptomycin production by Streptomyces griseus at elevated growth
      temperature: studies using gene fusions.
AB  - Streptomyces griseus ATCC 12475 fails to produce streptomycin when grown at 34
      degrees C or above, although growth is appreciable up to at least 37 degrees C.
      This depression of streptomycin production at elevated growth temperature is
      manifest equally in liquid and on solid, and with complex and minimal, media. We
      report studies with gene fusions of the reporter genes aph or xyIE to restriction
      fragments containing the streptomycin biosynthesis promoter PstrB1. aph
      constructs were in high, and xyIE constructs in low, copy number vectors. Two
      strB1 promoter fragments were used, one requiring activation by the pathway
      specific activator StrR of S. griseus, the other reportedly activator
      independent. PstrB1 expression in the aph constructs in S. griseus and in S.
      lividans was significantly reduced at 37 degrees C compared to 30 degrees C. Some
      of this reduction could be explained by lower plasmid copy number at the higher
      temperature, but strR-dependent expression was clearly temperature controlled.
      Using the xyIE reporter system, the temperature dependence of PstrB1 expression
      was confirmed but, surprisingly, the strR dependence of the two promoter
      fragments differed from that observed in the multicopy aph constructs. These data
      identify a temperature-dependent promoter which may contribute to the depressive
      effect of elevated growth temperature on streptomycin production.

PMID- 7582011
TI  - The tuf3 gene of Streptomyces coelicolor A3(2) encodes an inessential elongation
      factor Tu that is apparently subject to positive stringent control.
AB  - In Streptomyces coelicolor A3(2), two genes, tuf1 and tuf3, encode the apparent
      polypeptide chain elongation factors EF-Tu1 and EF-Tu3, respectively. While tuf1
      appears to code for the major EF-Tu, the function of tuf3 is unknown. To assess
      the role of EF-Tu3, tuf3 was subjected to mutational and transcriptional
      analyses. Replacement of the 5'-half of tuf3 by an antibiotic resistance cassette
      had no detectable effect on phenotype, indicating that tuf3 is not essential for
      growth or differentiation. The transcription start site of tuf3 was located
      approximately 195 nt upstream of the translation start site. The sequence of the
      tuf3 promoter (Ptuf3) resembles the consensus for the major class of eubacterial
      promoters, and Ptuf3 was recognized preferentially by an RNA polymerase fraction
      enriched in sigma hrdB, the principal sigma factor of S. coelicolor. Nuclease S1
      mapping failed to reveal tuf3 transcripts during growth of S. coelicolor in
      liquid culture, consistent with the apparent absence of EF-Tu3 in total protein
      extracts of the same strain. However, tuf3 transcription was observed in cultures
      of S. coelicolor M145 shortly after nutritional shiftdown (which resulted in the
      disappearance of tuf1 transcripts) and after addition of serine hydroxamate, both
      of which induce the stringent response. Transcription of tuf3 was also observed
      in transition-phase and stationary-phase cultures of S. coelicolor J1681, a
      strain deleted for bldA (which specifies a tRNA(Leu) for the rare leucine codon
      UUA). In all of these examples, transcription of tuf3 followed the production of
      ppGpp, consistent with the hypothesis that tuf3 is subject to positive stringent
      control.

PMID- 7582012
TI  - Response of the bvg regulon of Bordetella pertussis to different temperatures and
      short-term temperature shifts.
AB  - Bordetella pertussis produces a number of virulence factors whose expression is
      coordinately regulated by the bvgAS locus. Transcription of virulence genes is
      repressed by environmental factors such as low temperature (25 degrees C) and
      chemical stimuli. Temperature shift of bacterial cultures from 25 degrees C to 37
      degrees C activates two classes of bvg-regulated virulence genes: the early
      genes, which are activated within 10 min, and late genes, which require 2-4 h for
      activation. During the interval between the activation of the early and late
      genes, the intracellular concentration of BvgA increases 50-fold. It has been
      proposed that this increased concentration may be required for the activation of
      the late genes. Here we have analysed the response of the bvg locus to
      intermediate temperature and to repeated temperature shifts. Temperature shifts
      of B. pertussis cultures from 22 degrees C to 28 degrees C or 35 degrees C
      resulted in the synthesis of low, intermediate, and high amounts of BvgA. This
      implied that the intracellular concentration of BvgA is temperature-dependent. We
      have also observed that the amount of virulence factors produced correlates with
      the BvgA concentration. When bacteria grown at 37 degrees C were shifted to 22
      degrees C, transcription from the adenylate cyclase toxin haemolysis promoter
      (PAC) was repressed after 30 min, while transcription from the bvg (P1) and
      filamentous haemagglutinin (PFHA) promoters was repressed after 2 h. During this
      time, the amount of BvgA did not decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582013
TI  - A 17 kDa outer-membrane protein (Omp4) from Serratia marcescens confers partial
      resistance to bacteriocin 28b when expressed in Escherichia coli.
AB  - A cosmid-based genomic library of Serratia marcescens N28b was introduced into
      Escherichia coli and clones were screened for a bacteriocin 28b insensitive
      phenotype. One clone was found that showed partial resistance to bacteriocin 28b.
      By using Tn5tac1 insertions it was shown that this phenotype was due to the
      expression in E. coli of an outer-membrane protein of 17 kDa (Omp4). The DNA
      region defined by insertion mutagenesis was sequenced and found to contain an ORF
      of 515 bp. The deduced amino acid sequence has 172 residues with a theoretical
      molecular mass of 18.4 kDa. The protein contains an N-terminal signal sequence of
      24 amino acid residues and, when compared to other enterobacterial outer-membrane
      proteins, most closely resembles a family of small outer-membrane proteins of
      Enterobacteriaceae whose known functions appear to be related with virulence.
      Immunoblotting experiments showed that Omp4 is present in 15 biotypes of S.
      marcescens. The bacteriocin 28b resistance phenotype conferred on E. coli by Omp4
      appears to be pleiotropic since overexpression of the Omp4-encoding gene leads to
      a decrease in the amount of OmpA, OmpF and/or OmpC; OmpA and OmpF are the
      receptors for bacteriocin 28b in E. coli.

PMID- 7582014
TI  - Nucleotide sequence of the mxcQ and mxcE genes, required for methanol
      dehydrogenase synthesis in Methylobacterium organophilum XX: a two-component
      regulatory system.
AB  - Nucleotide sequence analysis of the mxcQ and mxcE loci, required for the
      synthesis of methanol dehydrogenase in Methylobacterium organophilum XX, has
      revealed two open reading frames that show significant similarity to sequences of
      prokaryotic two-component systems, especially MxaY and MxaX proteins of another
      methylotrophic bacterium, Paracoccus denitrificans. Cell-free extracts and DNA
      column-fractionated proteins from wild-type M. organophilum XX cells grown on
      methanol or succinate contained protein(s) that were able to bind specifically to
      the upstream region of methanol dehydrogenase large subunit gene (mxaF). In
      contrast, cell-free extracts from mxcQ and mxcE mutant strains of M. organophilum
      XX had zero or reduced binding activity towards the promoter fragments of the
      mxaF gene. This is consistent with the involvement of the mxcQ and mxcE genes in
      transcriptional regulation of methanol dehydrogenase synthesis. Analyses of
      sequential deletions of the mxaF upstream region have defined the functional
      boundary of the promoter/operator region of this gene and identified one
      nucleotide segment as essential to the activation of mxaF.

PMID- 7582015
TI  - Poly-beta-hydroxybutyrate (PHB) biosynthetic genes in Rhizobium meliloti 41.
AB  - Genes encoding beta-ketothiolase (phaA), acetoacetyl-CoA reductase (phaB) and PHB
      synthase (phaC) from R. meliloti 41, together with a fourth gene, referred to as
      ORF1, presumed to be involved in PHB biosynthesis, have been cloned and
      sequenced. phaA, phaB and ORF1 were identified by heterologous hybridization on a
      cosmid library, while phaC was isolated by cloning the transposon-tagged fragment
      from a R. meliloti PHB- Tn5 mutant. phaA and phaB were functionally expressed in
      Escherichia coli while phaC was able to complement a PHB- strain of R. meliloti
      41. The three genes were sufficient to direct the production of
      polyhydroxyalkanoate in E. coli. The homology of ORF1 with an ORF located near
      the PHB genes in two phototrophic bacteria suggests its involvement in PHB
      synthesis.

PMID- 7582016
TI  - An isoleucyl-tRNA synthetase gene from Campylobacter jejuni.
AB  - A complete isoleucyl-tRNA synthetase gene (ileS) of Campylobacter jejuni was
      isolated from a C. jejuni TGH9011 genomic DNA library constructed in pBluescript.
      The complete coding sequence, flanking regions and transcription start point were
      determined. The deduced isoleucyl-tRNA synthetase (IleRS) had 917 amino acids
      with a molecular mass of 105,399 Da, which was consistent with the observed size
      of 105 kDa in Escherichia coli maxicells. The ileS gene was mapped onto the
      physical map of the C. jejuni genome. Alignment of the C. jejuni IleRS sequence
      with six other bacterial IleRS sequences and two lower eukaryotic IleRS sequences
      identified seven conserved motifs, including the two signature sequences, HIGH
      and KMSKS, of class I aminoacyl-tRNA synthetases.

PMID- 7582017
TI  - Molecular analysis of an extracellular protease gene from Vibrio
      parahaemolyticus.
AB  - The structural gene prtVp encoding the extracellular protease of Vibrio
      parahaemolyticus strain 93 was cloned in Escherichia coli and sequenced. The
      cloned DNA fragment contained a 1761 bp ORF encoding a 587 amino acid protein.
      The deduced polypeptide is composed of a 25 amino acid signal peptide and a 562
      amino acid extracellular polypeptide with a calculated molecular mass of 63,156
      Da. Protease analysis using a gelatin-containing SDS-polyacrylamide gel detected
      the presence of a 62 kDa protease that was present in the culture supernatant
      fractions of the wild-type V. parahaemolyticus strain and of E. coli bearing a
      pUC119 recombinant with the prtVp DNA insert. The protease activity was inhibited
      by zinc- and metal-specific inhibitors such as EDTA and 1,10-phenanthroline,
      which suggested that it is a metalloprotease. The deduced amino acid sequence of
      PrtVp has 32% identity with that of the collagenase of Vibrio alginolyticus, but
      has no identity with those of the bacterial proteases. A conserved zinc-binding
      domain was also found in PrtVp from homology comparison with other
      metalloproteases. This PrtVp can cause weak haemolysis on blood agar.

PMID- 7582018
TI  - Characterization of cryptic prophages (monocins) in Listeria and sequence
      analysis of a holin/endolysin gene.
AB  - Monocins in Listeria were induced by UV-irradiation of liquid cultures, and
      defective phage particles were purified from the lysates. Electron microscopy
      showed flexible, non-contractile bacteriophage-tail-like particles, consisting of
      specific proteins of molecular mass 20-45 kDa and pI 4.6-6.7. These particles
      were able to lyse listerial cells. DNA sequence homologies between chromosomal
      DNA of monocin-producing strains and labelled Listeria phage DNAs were inferred
      from DNA/DNA hybridizations, suggesting that most of the prophage DNA is still
      present in the listerial chromosome. An endolysin gene cpl2438 was cloned from
      listerial chromosomal DNA and was identified by its expression of lytic activity
      against Listeria cells in a bioassay. The gene consists of 864 nt encoding a
      protein of 287 aa with a calculated molecular mass of 32975 Da (CPL2438). This is
      in good agreement with the size of a protein observed in SDS-PAGE after
      overexpression of the lytic protein in Escherichia coli. The nucleotide sequence
      of a putative holin gene (hol2438, 291 nt) upstream of cpl2438 was determined
      after PCR-amplification of listerial DNA and it shows typical features common to
      the holin gene family. Expression of the encoded protein (HOL2438, 95 aa, 10.1
      kDa) in E. coli was found to be lethal for the host cells. The results underline
      the close relationship between monocins and intact Listeria bacteriophages,
      indicating that monocins are incompletely assembled phage particles derived from
      cryptic prophages of Listeria, probably including the phage lysin.

PMID- 7582020
TI  - The DNA and RNA polymerase genes of yeast plasmid pGKL2 are essential loci for
      plasmid integrity and maintenance.
AB  - Novel recombinant plasmids derived from the Kluyveromyces lactis killer plasmid
      k2 have been constructed to study plasmid biology and gene function. In vivo
      recombination between native resident k2 and suitable disruption vectors,
      employing the KITRP1 gene fused to a plasmid promoter as selection marker,
      yielded ORF2 and ORF6 deletion plasmids at high frequencies. As judged from
      Southern hybridization and plasmid restriction mapping analyses, these novel
      hybrids, termed rk2/2 and rk2/6, respectively, carry deletions in their putative
      DNA (ORF2) and RNA (ORF6) polymerase structural genes with central regions
      replaced by the input marker DNA. Long-term selection for TRP1 over 350
      generations of growth did not favour maintenance of hybrids over wild-type k2.
      Thus, neither rk2/2 nor rk2/6 was fully functional and able to displace parental
      k2, indicating that both target genes are essential for plasmid integrity or
      maintenance. Recombinant plasmids were reduced in copy number relative to k2 with
      rk2/2 more drastically affected than rk2/6 implying a direct involvement of the
      ORF2 product in plasmid replication and an indirect maintenance function for the
      ORF6 gene product.

PMID- 7582019
TI  - A plasmid encoding enzymes for nylon oligomer degradation: nucleotide sequence
      and analysis of pOAD2.
AB  - The entire nucleotide sequence of nylon oligomer degradative plasmid pOAD2 from
      Flavobacterium sp. KI723T1 was determined. pOAD2 comprises 45519 bp, with a 66.6
      mol% G+C content. The precise loci of the four nylon oligomer degradation genes,
      namely nylA (6-aminohexanoate-cyclic-dimer hydrolase gene), nylB (6
      aminohexanoate-dimer hydrolase), nylB' (a gene having 88% homology to nylB) and
      nylC (endo-type 6-aminohexanoate oligomer hydrolase), and five IS6100 elements
      were identified on this plasmid. Comparison of the sequence of pOAD2 with those
      in the GenBank and EMBL databases revealed that the deduced amino acid sequences
      from eight regions of pOAD2 had significant similarity with the sequences of gene
      products such as oppA-F (oligopeptide permeases), ftsX (filamentation temperature
      sensitive), penDE (isopenicillin N-acyltransferase) and rep (plasmid
      incompatibility). A functional map of pOAD2 is presented.

PMID- 7582021
TI  - Agrobacterium radiobacter and related organisms take up fructose via a binding
      protein-dependent active-transport system.
AB  - Washed cells of Agrobacterium radiobacter prepared from a fructose-limited
      continuous culture (D 0.045 h-1) transported D(-)[U-14C]fructose in a linear
      manner for up to 4 min at a rate several-fold higher than the rate of fructose
      utilization by the growing culture. D(-)[U-14C]Fructose transport exhibited a
      high affinity for fructose (KT < 1 microM) and was inhibited to varying extents
      by osmotic shock, by the uncoupling agent carbonyl cyanide p
      trifluoromethoxyphenylhydrazone, and by unlabelled sugars (D-fructose/D-mannose >
      D-ribose > D-sorbose > D-glucose/D-galactose/D-xylose; no inhibition by D
      arabinose). Prolonged growth of A. radiobacter in fructose-limited continuous
      culture led to the selection of a novel strain (AR100) which overproduced a
      fructose-binding protein (FBP) and showed an increased rate of fructose
      transport. FBP was purified from osmotic-shock fluid using anion-exchange fast
      protein liquid chromatography (FPLC). The monomeric protein (M(r) 34,200 by SDS
      PAGE and 37,700 by gel-filtration FPLC) bound D-[U-14C]-fructose
      stoichiometrically (1.17 nmol nmol FBP-1) and with high affinity (KD 0.49 microM)
      as shown by equilibrium dialysis. Binding of D-[U-14C]fructose by FBP was
      variably inhibited by unlabelled sugars (D-fructose/D-mannose > D-ribose > D
      sorbose; no inhibition by D-glucose, D-galactose or D-arabinose). The N-terminal
      amino acid sequence of FBP (ADTSVCLI-) was similar to that of several sugar
      binding proteins from other species of bacteria. Fructose transport and FBP were
      variably induced in batch cultures of A. radiobacter by growth on different
      carbon sources (D-fructose > D-ribose/D-mannose > D-glucose; no induction by
      succinate). An immunologically similar protein to FBP was produced by
      Agrobacterium tumefaciens and various species of Rhizobium following growth on
      fructose. It is concluded that fructose is transported into A. radiobacter and
      related organisms via a periplasmic fructose/mannose-binding-protein-dependent
      active-transport system, in contrast to the phosphotransferase system used by
      many other species of bacteria.

PMID- 7582022
TI  - Acetyl-CoA-dependent pyruvate carboxylase from the photosynthetic bacterium
      Rhodobacter capsulatus: rapid and efficient purification using dye-ligand
      affinity chromatography.
AB  - Pyruvate carboxylase (PC) was purified to homogeneity from an overexpressing
      strain of the purple photosynthetic bacterium Rhodobacter capsulatus using a
      rapid dye-ligand affinity chromatography procedure, in which dye-bound enzyme was
      specifically eluted with a low concentration of acetyl-CoA, an allosteric
      activator of the enzyme. The enzyme purified by this method was obtained in 75%
      yield with a specific activity of 40 U (mg protein)-1. In contrast, affinity
      chromatography on a monomeric avidin column, commonly used in the purification of
      biotin-containing carboxylases, resulted in a yield of < 40%, with a specific
      activity of 10 U (mg protein)-1. The enzyme purified by the dye-linked procedure
      had a subunit molecular mass of 140,000 Da and was absolutely dependent on acetyl
      CoA for activity. Acetyl-CoA was also effective in protecting the enzyme from
      thermal denaturation. The enzyme was inhibited by 2-oxoglutarate and, to a lesser
      extent, L-aspartate, with sigmoidal kinetics with respect to acetyl-CoA
      concentration. The amino acid composition, pH optimum and kinetic constants for
      pyruvate, ATP and bicarbonate were determined. An N-terminal sequence of 26
      residues was obtained, which was homologous to the N-terminal regions of several
      eukaryotic PCs, propionyl-CoA carboxylases and acetyl-CoA carboxylase.

PMID- 7582023
TI  - A new chitosanase gene from a Nocardioides sp. is a third member of glycosyl
      hydrolase family 46.
AB  - Strain N106, a newly isolated soil actinomycete classified in the genus
      Nocardioides on the basis of its chemotaxonomy, produced an extracellular
      chitosanase and was highly active in chitosan degradation. A gene library of
      Nocardioides sp. N106 was constructed in the shuttle vector pFD666 and
      recombinant plasmids carrying the chitosanase gene (csnN106) were identified
      using the 5'-terminal portion of the chitosanase gene from Streptomyces sp. N174
      as a hybridization probe. One plasmid, pCSN106-2, was used to transform
      Streptomyces lividans TK24. The chitosanase produced by S. lividans (pCSN106-2)
      is a protein of 29.5 kDa, with a pI 8.1, and hydrolyses chitosan by an endo
      mechanism giving a mixture of dimers and trimers as end-products. N-terminal
      sequencing revealed that the mature chitosanase is a mixture of two enzyme forms
      differing by one N-terminal amino acid. The csnN106 gene is 79.5% homologous to
      the csn gene from Streptomyces sp. N174. At the amino acid level, both
      chitosanases are homologous at 74.4% and hydrophobic cluster analysis revealed a
      strict conservation of structural features. This chitosanase is the third known
      member of family 46 of glycosyl hydrolases.

PMID- 7582025
TI  - A gene (sleC) encoding a spore-cortex-lytic enzyme from Clostridium perfringens
      S40 spores; cloning, sequence analysis and molecular characterization.
AB  - Antiserum was raised against a 31 kDa spore-cortex-lytic enzyme, which is
      released during germination of Clostridium perfringens S40 spores. Western
      blotting of dormant spore and vegetative cell fractions separated by SDS-PAGE
      indicated that the 31 kDa enzyme is spore-specific and that the enzyme in the
      dormant spore exists as a 36 kDa protein which has no cortex-lytic activity. A
      gene encoding the 31 kDa enzyme, sleC, was cloned into Escherichia coli using a
      synthetic oligonucleotide as a hybridization probe and the nucleotide sequence of
      the entire gene was determined. The N-terminal amino acid sequence of the 36 kDa
      protein was found in this reading frame, confirming that the 36 kDa protein is a
      pro-form of the 31 kDa enzyme. The deduced amino acid sequence indicated that the
      31 kDa enzyme is produced as a precursor, comprising three portions; an N
      terminal prepro-sequence (114 amino acid residues), a pro-sequence (35 amino acid
      residues) and a mature enzyme (289 amino acid residues). It is suggested that the
      36 kDa pro-enzyme is non-covalently attached to the exterior of the cortex layer,
      and that the proform is processed to release the active enzyme during
      germination.

PMID- 7582024
TI  - Uptake of amino acids by the parasitic, flagellated protist Trichomonas
      vaginalis.
AB  - HPLC techniques have been applied to study amino acid uptake and release by
      Trichomonas vaginalis under a variety of conditions. Studies on the growth of T.
      vaginalis in complex media and the survival of the parasite in simple media, with
      and without amino acids and/or maltose, have shown that the growth or survival of
      T. vaginalis is better in the presence of maltose than when it is absent, and
      that greater amounts of amino acids are consumed by T. vaginalis in the absence
      of maltose. The results are consistent with several amino acids, notably
      arginine, threonine, leucine and methionine, being used by T. vaginalis as energy
      substrates. T. vaginalis released alanine and glycine into the culture media, the
      excretion being greater in the presence of maltose. These studies have provided
      new data on the uptake and release of amino acids by T. vaginalis and pave the
      way for detailed analysis of key enzymes and the regulation of the pathways
      involved.

PMID- 7582026
TI  - Isolation of canCHS1A, a variant gene of Candida albicans chitin synthase.
AB  - A canCHS1A gene encoding the chitin synthase of Candida albicans was cloned. DNA
      sequencing and comparison with another canCHS1 gene described elsewhere indicated
      that the canCHS1A gene encoded a polypeptide with 775 amino acid residues, a
      protein with one less amino acid than that encoded by the canCHS1 gene. A six
      base alteration was observed between the two genes, suggesting that the canCHS1A
      gene is a variant gene of the canCHS1. The pH profile/activity relationship of
      canChs1A in permeabilized cells was identical to that of canChs1. The canChs1A
      enzyme was competitively inhibited by polyoxin D (5.2 microM) and nikkomycin Z
      (12 microM). When the cloned gene was expressed in a Saccharomyces cerevisiae
      chs2 mutant that exhibited aberrant morphology, the normal structure was
      restored. We conclude that the function of the canCHS1A gene is similar to that
      of sacCHS2 in S. cerevisiae.

PMID- 7582027
TI  - Gelatin fragments block adherence of Candida albicans to extracellular matrix
      proteins.
AB  - The adherence of Candida albicans to extracellular matrix proteins may be a
      critical step in the pathogenesis of candidiasis. Yeast cell adherence to type I
      and IV collagen, fibronectin and laminin was blocked by peptide fragments from
      denatured type I collagen (gelatin). Gelatin fragments were obtained by digestion
      of the reduced protein with trypsin or CNBr. The fragments did not have
      antifungal properties, presumably inhibiting adherence by blocking receptors
      (adhesins) on the surface of the fungus. A 10-mer (GQRGVVGLPG) fashioned from the
      alpha-1 chain of type I collagen reduced adherence by 68%. However, a gelatin
      peptide possessing 47 amino acids reduced fungal adherence to type I collagen by
      100%. Peptides derived from the biocompatible protein gelatin, therefore, may
      have a potential role in reducing the adherence of the fungus to host proteins.

PMID- 7582028
TI  - Oestrogen-binding protein in Candida albicans: antibody development and cellular
      localization by electron immunocytochemistry.
AB  - Candida albicans, the most common fungal pathogen of humans, possesses an
      oestrogen (estrogen)-binding protein (EBP) that binds oestrogens with high
      affinity and specificity. The gene that encodes the EBP (CaEBP1) has been cloned
      and sequenced and shown to be structurally related to the old yellow enzyme from
      Saccharomyces cerevisiae. Here, we report the purification and the subcellular
      localization of the EBP from C. albicans. Using ion-exchange chromatography and
      an oestradiol affinity column, the EBP was purified from a strain of C. albicans
      (strain 422) which was selected because it constitutively expressed elevated
      levels of the binding protein. The purified protein displayed a subunit molecular
      mass of approximately 46 kDa when examined by denaturing gel electrophoresis,
      which is consistent with the size estimated from the sequence of the cloned
      CaEBP1 gene. An immunoaffinity column, prepared using a polyclonal antisera
      generated against EBP, depleted the oestrogen-binding activity from C. albicans
      cell extracts. Western blot analysis showed that the antisera specifically
      recognized the EBP from C. albicans. The antibodies also recognized the protein
      when the cloned CaEBP1 gene was expressed in S. cerevisiae and did not cross
      react with S. cerevisiae proteins. Using electron microscopy and antigen
      detection by immunogold staining, the EBP appeared to be primarily associated
      with vacuoles. However, when overexpressed in S. cerevisiae, the EBP was found
      diffusely throughout the cell. In conclusion, the EBP has been purified from C.
      albicans and antibodies generated against the protein were used to demonstrate
      that EBP is found associated with vacuoles in C. albicans.

PMID- 7582029
TI  - Mapping of beta-1,2-linked oligomannosidic epitopes among glycoconjugates of
      Candida species.
AB  - The distribution of beta-1,2-linked oligomannosides among glycoconjugates of
      various Candida species was investigated by Western blotting, using monoclonal
      and polyclonal antibodies which react with these epitopes. Expression of beta-1,2
      linked oligomannosidic epitopes on a 14-18 kDa polydisperse antigen nonreactive
      with concanavalin A (ConA), previously identified as a C. albicans serotype A
      phospholipomannan (PLM), appeared to be restricted to C. albicans serotypes A and
      B (including var. C. stellatoidea types I and II) and C. tropicalis. In C.
      albicans, beta-1,2-linked oligomannosidic epitopes also appeared to be slightly
      associated with high molecular mass (> 100 kDa) polydisperse ConA-reactive
      mannoproteins. For all the other Candida strains investigated, belonging to the
      species C. parapsilosis, C. krusei, C. glabrata and C. robusta (S. cerevisiae),
      beta-1,2-linked oligomannosidic epitopes were found to be present in association
      with medium molecular mass (18-100 kDa) and high molecular mass ConA-reactive
      mannoproteins, giving reproducible labelling profiles that varied between
      species.

PMID- 7582030
TI  - Aspergillus fumigatus antigens.
AB  - Cytosolic fractions of mycelial extracts from Aspergillus nidulans, A. flavus,
      and three different isolates of A. fumigatus, grown to stationary phase in Czapek
      Dox-AOAC medium, were tested by immunoblotting for the presence of antigens
      reactive to 80 serum samples from aspergilloma patients. Fifty control serum
      samples were used to determine the specificity of the reactions. In the A.
      fumigatus cytosolic fraction a group of four main antigenic bands (p90, p60, p40
      and p37) was consistently recognized (in total or partial form) by 90% of the
      serum samples from the aspergilloma patients. This group of antigens was
      designated as the 'cytosolic fraction complex' (CFC). As confirmed by two
      dimensional electrophoresis followed by immunoblotting with aspergilloma serum
      samples, each of the four antigenic bands is formed of several isoforms of acidic
      glycopeptides with slightly different pls. All the isoforms are at least N
      glycosylated, as demonstrated by endoglycosidase H removal of a considerable
      amount of sugar residues. The relationship of these antigens with certain other
      A. fumigatus antigens previously reported in the literature, and their potential
      use in the immunodiagnosis of aspergilloma, are discussed.

PMID- 7582031
TI  - A highly immunogenic putative Mycobacterium kansasii lipoprotein.
AB  - The resurgence of tuberculosis, the emergence of multiple drug resistant
      tuberculosis, and the increasing prevalence of mycobacterial disease in AIDS
      patients have increased the importance of defining new mycobacterial antigens
      that can be utilized in the development of improved diagnostic reagents and more
      effective vaccines. In this report, a highly immunogenic Mycobacterium kansasii
      protein (MK35) and the gene encoding this antigen were characterized. MK35 gene
      probes reacted with genomic DNA from M. avium, M. bovis BCG, M. intracellulare
      and M. tuberculosis but not with DNA isolated from nine other mycobacterial
      species. Nucleotide sequence analysis showed that the MK35 gene encodes a 26 kDa
      protein which contains a consensus bacterial lipoprotein processing sequence. In
      addition, detergent-phase separation studies strongly suggested that MK35 is a
      lipoprotein. Skin test assays demonstrated that MK35 elicited a strong response
      in guinea pigs sensitized with M. kansasii but did not react in M. tuberculosis
      sensitized guinea pigs. These results further suggest that mycobacterial
      lipoproteins are immunogenic antigens that should be considered in the
      development of new mycobacterial vaccines and diagnostic reagents.

PMID- 7582032
TI  - The use of two-dimensional gradient plates to investigate the range of conditions
      under which conjugal plasmid transfer occurs.
AB  - Gel-stabilized two-dimensional gradient plates were used to study the effects of
      pH, salt concentration and temperature on the conjugal transfer of plasmid RP4
      between strains of Escherichia coli and Pseudomonas putida. The combinations of
      pH and salt concentration that permitted conjugation were mapped as a two
      dimensional growth area occupied by transconjugants following conjugation. This
      conjugation domain was less extensive than the areas that supported growth of the
      parental strains, and showed evidence for the interactive effects of pH and salt
      concentration in determination of conditions that permitted conjugation. The size
      and shape of the conjugation domain was influenced by time, temperature, the
      identities of the donor and recipient bacteria, and the combination of donor and
      recipient bacteria.

PMID- 7582033
TI  - High frequency of conjugation versus plasmid segregation of RP1 in epiphytic
      Pseudomonas syringae populations.
AB  - The maintenance and transfer of the broad host-range plasmid RP1 in epiphytically
      growing populations of Pseudomonas syringae was monitored in the phyllosphere of
      bush bean (Phaseolus vulgaris). When foliage was inoculated with plasmid
      containing bacteria, the plasmid was lost from the majority of the cells within 2
      d but was stably maintained in 0.8% of the population. A high frequency of
      conjugation between added donors and recipients was observed under high humidity
      conditions. In 1 d, the number of transconjugants rose to 10(-1) of the donors
      and the proportional level of transconjugants continued to increase until 3 d
      after inoculation. Under these conditions the proportion of plasmid-containing
      bacteria stabilized at about 0.8% of the total population. The conjugation rate
      appeared to be in equilibrium with plasmid loss and the slower growth of the
      plasmid-carrying cells. A factor that influenced the high conjugation frequency
      observed was the available nutrients provided by the leaf and also, to a lesser
      extent, the leaf surface itself. Transfer of the plasmid from added donors to
      indigenous bacteria was also studied, using a donor-specific bacteriophage for
      counterselection of the donor. Transfer was observed to 10 different species of
      Gram-negative epiphytically growing bacteria. The bean leaf surface appears to
      function as a hotspot at least for intraspecific transfer of plasmids in high
      humidity. The frequency of transfer was higher than in soil or in rhizosphere
      habitats. This is likely to be the result of an environment that is nutritionally
      rich in combination with a limited colonizable surface area which permits close
      contact between the bacterial cells.

PMID- 7582035
TI  - Role of LPS length in clearance rate of bacteria from the bloodstream in mice.
AB  - Strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis
      (CF) never spread systemically. This may be due to serum sensitivity since these
      strains are very sensitive to complement-mediated bactericidal activity. A serum
      resistant mutant, P. aeruginosa TUM3 HSR, was obtained from serum-sensitive
      strain TUM3 from a CF patient in order to clarify the mechanism of failure of
      systemic spread. LPS profiles on silver-stained gels and immunological analysis
      revealed that a long O-polysaccharide side chain was overproduced on the LPS
      molecules of TUM3 HSR as compared with the LPS of TUM3. The clearance rate from
      the bloodstream in mice was compared in the two strains. The number of TUM3
      bacteria in 1 ml of blood, 10 min after injection into the tail vein,
      significantly decreased from 1.7 x 10(8) to 3.7 x 10(5) c.f.u. ml-1. In contrast,
      TUM3 HSR was not eliminated during the same period (decrease from 1.9 x 10(8) to
      3.4 x 10(7) c.f.u. ml-1). Interestingly, these isogenic strains were not killed
      by 40% murine serum, probably reflecting immaturity of the complement-mediated
      killing system in mice. These results pointed to a correlation between LPS
      structure and blood clearance rate in mice. This was confirmed by examining blood
      clearance kinetics using the smooth-LPS strain Salmonella typhimurium LT2 and LPS
      deficient mutants derived from it. S. typhimurium LT2 resisted blood clearance
      while the LPS-deficient mutants were cleared rapidly. None of the S. typhimurium
      strains were killed by murine serum. The number of P. aeruginosa TUM3 and S.
      typhimurium LPS-deficient mutants trapped in the liver following injection into
      the peripheral circulation was greater than that of their counterparts.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582034
TI  - Ribosomal internal transcribed spacer sequences are identical among Mycobacterium
      avium-intracellulare complex isolates from AIDS patients, but vary among isolates
      from elderly pulmonary disease patients.
AB  - Sequencing 280 bp of the internal transcribed spacer (ITS) between the 16S and
      23S rRNA genes in a collection of 46 clinical isolates of the Mycobacterium avium
      intracellulare complex (MAI complex) identified nine different sequences,
      grouping these isolates in nine 'ITS sequevars'. This analysis extends the
      subdivision within the MAI complex to 18 ITS sequevars and also improves
      discrimination from other mycobacterial species. Evaluation of the sequevar
      grouping among different clinical sources revealed strong association of the M.
      avium sequevar Mav-B with AIDS and with lymphadenitis in children (18 out of 20
      and 3 out of 3 respectively). Isolates from elderly patients with pulmonary
      disease and not suspected of being HIV infected belonged predominantly to M.
      intracellulare ITS sequevars and sequevars not assigned to either M. avium or M.
      intracellulare. On the other hand, animal isolates were of both the Mav-A and Mav
      B sequevars. We conclude that ITS sequevar typing is an accurate way of
      identifying distinct MAI complex strains. The observed differences between
      clinical sources suggest that ITS sequevars reflect possibly important,
      biologically and clinically relevant polymorphisms between MAI complex organisms.

PMID- 7582037
TI  - Movement disorders.

PMID- 7582038
TI  - Degenerative diseases.

PMID- 7582036
TI  - Unsaturated fatty acids are the active molecules of a glucan-synthase-inhibitory
      fraction isolated from entomophthoralean protoplasts.
AB  - A few entomophthoralean species are able to multiply in a protoplast form. The
      polysaccharide synthases which synthesize the cell wall are inactivated in this
      form. An inhibitor of one of the key enzymes of wall synthesis, glucan synthase,
      was isolated from entomophthoralean protoplasts, using silica column
      chromatography and HPLC. Thin-layer and gas chromatography revealed free fatty
      acids in the inhibitory fractions. These fatty acids, including long-chain
      unsaturated fatty acids, were shown to be responsible for the inhibition of
      glucan synthase. The fatty acids were generated during incubation of a protoplast
      homogenate for 36 h at 37 degrees C and were shown to be non-competitive and non
      specific inhibitors of glucan synthase.

PMID- 7582039
TI  - Cognitive problems in the elderly.
AB  - We have summarized the literature on cognitive changes in normal aging. The
      concepts of normal aging, age-associated memory impairment, and their possible
      continuum with dementia are discussed. Epidemiologic, genetic, radiological, as
      well as neuropsychological and endocrine contributions to the understanding of
      cognition in the elderly, are reviewed.

PMID- 7582040
TI  - Progress in Alzheimer's disease genetics.
AB  - Three genetic loci for Alzheimer's disease have been identified. These are the
      amyloid precursor gene on chromosome 21, a gene for early-onset autosomal
      dominant Alzheimer's disease on chromosome 14, and the risk-modifying gene APOE
      on chromosome 19. Additional Alzheimer's disease genes remain to be found. The
      genes identified by studying inherited forms of Alzheimer's disease are now being
      used to understand the initiating steps in the pathogenesis of the disease.

PMID- 7582042
TI  - Therapeutic trials in Alzheimer's disease.
AB  - Therapeutic trials activity in Alzheimer's disease increased during the past
      year, with both the initiation of new and the continuation of ongoing symptomatic
      treatment studies designed to demonstrate enhancement of cognitive abilities.
      Interest in interventions for noncognitive or behavioral symptoms has also
      increased. Attempts to convert new basic scientific discoveries into clinical
      approaches that slow the progression of the disease also generated enthusiasm.
      Timely consideration of certain critical methodological, ethical, and policy
      issues are likely to enhance this late phase activity in drug development in the
      years to come.

PMID- 7582041
TI  - Amyloid beta amyloidosis in Alzheimer's disease.
AB  - The presence of amyloid deposits in the parenchyma of the amygdala, hippocampus,
      and neocortex is a major histopathological hallmark of Alzheimer's disease. The
      principal component of amyloid is amyloid beta, a 39-43 amino acid peptide
      comprised of a portion of the transmembrane domain and the extracellular domain
      of the amyloid precursor proteins. Amyloid precursor proteins occur as several
      amyloid beta-containing isoforms of 695, 751, and 770 amino acids. In cultured
      cells, amyloid precursor proteins mature through the constitutive secretory
      pathway, and some cell-surface-bound amyloid precursor proteins are cleaved by an
      enzyme, designated as alpha-secretase, within the amyloid beta domain, an event
      that precludes amyloid beta amyloidogenesis. Two additional pathways of amyloid
      precursor protein processing include an endosomal/lysosomal pathway that
      generates a complex set of amyloid precursor protein-related membrane-bound
      fragments, some of which contain the entire amyloid beta sequence; and, by
      mechanisms not fully understood, secretion of amyloid beta 1-40 into the
      conditioned medium in vitro and its presence in cerebrospinal fluid in vivo. The
      intracellular sites of enzymes responsible for proteolytic cleavage at the amino-
      and carboxyl-termini of amyloid beta, termed gamma- and beta-secretase,
      respectively, have not been identified. Molecular genetic investigations have
      identified a variety of mutations in the amyloid precursor protein gene that
      segregate with early-onset familial Alzheimer's disease and with hereditary
      cerebral hemorrhage with amyloid, Dutch type. Several of these mutations appear
      to influence amyloid precursor protein processing and result in the production of
      higher levels or longer amyloid beta-related peptides that are inherently more
      fibrillogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582043
TI  - Non-Alzheimer's disease amyloidoses of the nervous system.
AB  - Amyloidosis and prionosis are disorders of protein conformation. The general
      mechanisms involved in amyloidogenesis are reviewed here. Recent progress in the
      molecular pathogenesis of cerebral amyloids is illustrated by three genetic
      disorders: hereditary amyloid angiopathies of Icelandic and Dutch origins and
      Gerstmann-Straussler-Scheinker disease.

PMID- 7582045
TI  - Motor neuron disease caused by mutations in superoxide dismutase 1.
AB  - A subset of pedigrees with dominant inheritance of familial amyotrophic lateral
      sclerosis have mutations in superoxide dismutase 1. Initial studies suggested
      that disease-linked mutations impaired superoxide dismutase 1 activity, which is
      consistent with the notion that disease results from increased oxidative injury.
      However, results of recent cell culture and transgenic studies demonstrate that
      mutant proteins retaining high levels of superoxide dismutase 1 activity cause
      motor neuron degeneration; elevating the level of wild-type superoxide dismutase
      1 does not cause disease. These findings suggest that the familial amyotrophic
      lateral sclerosis phenotype may occur through other mechanisms that can now be
      explored in model systems.

PMID- 7582044
TI  - Human prion diseases.
AB  - Major advances have been made in prion diseases. Recent data indicate that the
      prion protein is likely to be a synaptic protein with a functional role in
      synaptic transmission. An impressive body of evidence suggests that (1) the
      normal prion protein plays a central role in prion replication; (2) the
      replication process implies an interaction between the normal prion protein and
      the pathogenic prion protein; and (3) the pathogenic prion protein is the
      infectious agent, the infectivity of which is dependent on its abnormal
      conformation. Genetic and protein analyses have expanded the spectrum of prion
      diseases and have underlined the complexity of genotype-phenotype interactions.

PMID- 7582047
TI  - Inherited ataxias.

PMID- 7582048
TI  - Dopa-responsive dystonia.
AB  - The past 18 months have seen significant advances in our understanding of
      dopa(dihydroxyphenylalanine)-responsive dystonia. Clinical investigations have
      broadened the spectrum of disease with particular attention manifestations in
      infancy. Pathophysiological investigations have revealed features that
      distinguish dopa-responsive dystonia from childhood-onset parkinsonism. A
      pathological study has confirmed the 'developmental' nature of the disease.
      Finally, mutations causing the autosomal dominant form of dopa-responsive
      dystonia have been identified in the gene coding for GTP cyclohydrolase I.
      Mutations in tyrosine hydroxylase have been identified in two brothers and put
      forward as evidence of an autosomal recessive form of the disease.

PMID- 7582046
TI  - Some aspects of higher motor disorders and their relationship to movement
      disorders associated with disease of subcortical nuclei.

PMID- 7582049
TI  - Essential tremor and its variants.
AB  - Essential tremor is the commonest of movement disorders. Although sometimes
      prefaced with the term 'benign', it often causes significant disability.
      Diagnosis is based on the clinical finding of a postural tremor, predominantly
      affecting the upper limbs, that is absent at rest and not associated with
      extrapyramidal or cerebellar signs. There are, as yet, no specific anatomical,
      physiological, biochemical or genetic markers for the condition. Postural limb
      tremors, clinically indistinguishable from essential tremor, may occur in
      patients who have, or will later develop, other neurological conditions; whether
      such patients have essential tremor is a matter of controversy that will only be
      resolved with a better understanding of the pathophysiology of essential tremor.
      Positron emission tomography in patients with essential tremor reveals increased
      cerebellar activity even at rest, a finding that is consistent with the
      cerebellum having an important role in the generation of tremor. Abnormal
      cerebellar function has also been invoked to account for the abnormal manner in
      which patients with essential tremor perform rapid voluntary wrist movements.
      Molecular genetic studies in hereditary essential tremor have been initiated, but
      with negative results so far. Several new drug treatments have been tried, but
      with limited success; the role of thalamic stimulation and botulinum toxin in the
      treatment of essential tremor remains to be judged.

PMID- 7582051
TI  - Multiple system atrophy.
AB  - The past year has seen advances in delineating the clinical features, natural
      history and imaging characteristics of multiple system atrophy. The initiating
      pathogenetic mechanisms remain unknown. However, any aetiological or
      pathophysiological hypothesis must consider not only neuronal loss and gliosis
      but also the recently described characteristic oligodendrolial cytoplasmic
      inclusions.

PMID- 7582050
TI  - Symptomatic or secondary basal ganglia diseases and tardive dyskinesias.
AB  - This paper reviews clinical reports of various movement disorders (dystonia,
      chorea, ballism and parkinsonism) caused by well defined lesions of the putamen,
      globus pallidus, substantia nigra, thalamus and subthalamus. The role of basal
      ganglia in motor control is also emphasized.

PMID- 7582052
TI  - Management of parkinsonism and treatment of associated complications.
AB  - Management of Parkinson's disease is dominated by the desire to prevent the
      development of fluctuations, dyskinesia, and psychiatric complications, and to
      treat effectively these effects when they appear. Advances in the understanding
      of these complications and methods to manage them are reviewed.

PMID- 7582054
TI  - Miscoding of mental health diagnoses and stigmatization.

PMID- 7582053
TI  - Myoclonus.
AB  - Genetic studies have suggested homogeneity between the Baltic-type and
      Mediterranean-type progressive myoclonic epilepsy. Magnetoencephalography was
      applied to elucidate the mechanism underlying the giant evoked responses in
      cortical reflex myoclonus. A new concept of negative myoclonus mediated by
      cortical reflex mechanism was proposed. Cortical myoclonus was demonstrated in
      various neurodegenerative or metabolic disorders, such as presenile or senile
      dementia, olivopontocerebellar atrophy, and myoclonus epilepsy associated with
      ragged-red fibres. Myoclonus in corticobasal degeneration is especially
      noteworthy because it has clinical and electrophysiological features of cortical
      reflex myoclonus, but its latency is shorter compared with the conventional
      cortical reflex myoclonus. Clinical features of 'palatal myoclonus' were reported
      by the name of 'palatal tremor'.

PMID- 7582055
TI  - Rural health care.

PMID- 7582056
TI  - Harrison's.

PMID- 7582058
TI  - Whose data are these, anyway?

PMID- 7582057
TI  - Prevention, diagnosis, and management of viral hepatitis. A guide for primary
      care physicians. AMA Advisory Group on Prevention, Diagnosis, and Management of
      Viral Hepatitis.
AB  - This guide was developed to provide the primary care physician with essential
      practice information on viral hepatitis in a concise and useful format. An
      American Medical Association advisory panel, representative of all primary care
      specialty associations and nationally recognized experts, conducted a systematic
      review of the medical literature and prepared this physician guide with an
      emphasis on prevention, diagnosis, and management. The guide also underwent
      extensive peer review. Practical information on viral characteristics and
      epidemiology, clinical manifestations, diagnosis, management, and prevention is
      provided.

PMID- 7582059
TI  - The role of intuitive thinking in the diagnostic process.

PMID- 7582060
TI  - Does antihypertensive treatment of the elderly prevent cardiovascular events or
      prolong life? A meta-analysis of hypertension treatment trials.
AB  - OBJECTIVE: To estimate the short-term effects of drug treatment of hypertension
      in the elderly (> or = 60 years of age) on stroke, major coronary events, and
      mortality rates. DESIGN: Meta-analysis of all published randomized, controlled
      trials that addressed the impact of drug treatment of hypertension in the elderly
      on the above outcomes. SETTING AND PATIENTS: All published clinical trials that
      met the above criteria involved men and women recruited from primary care
      practices or through community screenings, who were then treated according to
      protocol at either community or specialty clinics. Eight randomized, controlled
      trials that included 15,990 patients treated for an average of 4.6 years were
      included in this meta-analysis. INTERVENTIONS: Patients received either active
      antihypertensive treatment or placebo in seven of the studies and programmed
      stepped care vs referral back to the usual care source in one study. MAIN OUTCOME
      MEASURES: Fatal or nonfatal myocardial infarction or sudden coronary death; fatal
      or nonfatal stroke; and all-cause mortality. Outcomes were analyzed on an
      intention-to-treat basis. RESULTS: Mean baseline blood pressure was 179/90 mm Hg,
      with a mean treatment effect of 15/6 mm Hg. Homogeneity tests indicated validity
      of the combined results. Pooled relative risks, calculated as treatment or
      control (with 95% confidence intervals) for the main end points, were as follows:
      fatal or nonfatal major coronary event, 0.82 (0.73 to 0.92); fatal or nonfatal
      stroke, 0.65 (0.57 to 0.75); and death from any cause, 0.85 (0.78 to 0.92) (P <
      .005 for each). CONCLUSION: Antihypertensive treatment in the elderly prevents
      major coronary events and stroke and prolongs life, with significant treatment
      effects observed within only 5 years.

PMID- 7582061
TI  - Attitudes of Dutch general practitioners and nursing home physicians to active
      voluntary euthanasia and physician-assisted suicide.
AB  - OBJECTIVE: To gain insight into the attitudes of Dutch general practitioners and
      nursing home physicians to voluntary active euthanasia and physician-assisted
      suicide. DESIGN: Descriptive study. METHOD: Data were collected by means of
      anonymous postal questionnaires to be completed by a random sample of 521 general
      practitioners from the province of North Holland, 521 general practitioners from
      the rest of the Netherlands, and 713 Dutch nursing home physicians who were
      members of the Dutch Association of Nursing Home Physicians. RESULTS: The written
      responses of general practitioners and nursing home physicians to six statements
      about voluntary active euthanasia and physician-assisted suicide showed that a
      large majority had a fairly positive attitude to euthanasia and suicide. This
      finding also emerged from the scores obtained on a scale compiled on the basis of
      the statements. General practitioners and nursing home physicians were more
      opposed to euthanasia and physician-assisted suicide if they had never performed
      it, if they belonged to a religious group, or if they were older. CONCLUSION:
      Dutch general practitioners and nursing home physicians have a fairly positive
      attitude toward euthanasia and physician-assisted suicide. However, the majority
      of these physicians favor a policy of voluntary active euthanasia and physician
      assisted suicide under strict conditions.

PMID- 7582063
TI  - Addiction to benzodiazepines--how common?
AB  - Benzodiazepines have compiled an impressive record of safety and efficacy.
      Despite this record, however, physicians and laypersons frequently worry about
      the drugs' addictive potential. Overemphasizing these concerns may discourage
      prescription of benzodiazepines, thereby impeding treatment of anxiety disorders.
      This review first defines the term addiction. It then examines how frequently
      conditions meeting that definition occur in patients without histories of
      substance abuse, who are prescribed benzodiazepines under medical supervision. In
      such patients, benzodiazepines almost never induce behavior that satisfies any
      reasonable definition of addiction.

PMID- 7582064
TI  - Intestinal perforation from trauma to an inguinal hernia.
AB  - Inguinal hernias are most feared to result in incarceration and strangulation of
      intra-abdominal structures. Blunt abdominal blows have previously been reported
      to cause traumatic perforation of bowel that overlays the defect of any abdominal
      wall hernia. To my knowledge, this case report is the first to show that bowel
      perforation may be caused by direct trauma to an inguinal hernia that contains a
      loop of small bowel. It is proposed that the force of the blow first opposes the
      walls of the incoming and outgoing bowel, sealing the loop. Then, additional
      pressure that is applied will raise the loop's intraluminal pressure to the point
      that traumatic perforation occurs. A simple experiment on a necropsy specimen
      showed that the proposed mechanism is plausible. This case points out another
      risk of leaving an inguinal hernia unrepaired.

PMID- 7582062
TI  - Experience of abuse in primary care patients. Racial and rural differences.
AB  - OBJECTIVE: To examine the experience of abuse in rural, urban, black, and white
      women on the following dimensions: prevalence, symptom experience, health status,
      medical services utilization, and coping mechanisms. DESIGN: Retrospective study
      using patient interviews. SETTING: Half the subjects were recruited from a large
      medical university family medicine center and half from a rural family medicine
      center, both in the Southeast. PATIENTS: Four hundred seven women were
      interviewed. Groups were distributed as follows: urban white, 24.9% (n = 99);
      urban black, 25.6% (n = 102); rural white, 11.1% (n = 44); and rural black, 38.4%
      (n = 153). MAIN OUTCOME MEASURES: Self-report of abuse (sexual, physical, and
      emotional) was related to symptom history, current health status, medical
      services utilization, and coping styles. RESULTS: Sixty-six percent of the total
      sample reported some kind of abuse. Black, rural women reported the least
      (52.3%). Presence of greater numbers of symptoms, greater medical services
      utilization, and lower health status were found in the abused population. Abused
      women used all types of coping mechanisms to a greater extent than non-abused
      women. Black women were more likely to use confrontation (F = 8.82 [P = .003]),
      problem solving (F = 8.24 [P = .004]), and reappraisal (F = 4.13 [P = .04]) than
      white women. Rural women were more likely to use psychological distancing (F =
      5.25 [P = .02]) and escape (F = 5.67 [P = .02]) than urban women, although abused
      women in general use those coping methods more than nonabused women. CONCLUSIONS:
      The experience of abuse remains similar across black, white, rural, and urban
      women; however, coping mechanisms appear to be influenced by group membership.

PMID- 7582065
TI  - Health care report cards. Validity of case definitions.
AB  - Administrative databases are increasingly being used to construct health care
      report cards. We analyzed information from one of the original report cards, the
      Medicare Hospital Information Project. Assessment of mortality statistics for
      three clinical entities--coronary artery bypass surgery, hip reconstruction, and
      treatment of sepsis--demonstrated widespread outcome variances that reflected
      imperfect definitions rather than performance issues in clinical care. The use of
      administrative data sets to design report cards requires clinical expertise to
      ensure validity of the data. Designers of report card measures should share
      preliminary data with providers to enable feedback in methods and uncover
      definitional and validity concerns before widespread dissemination.

PMID- 7582067
TI  - Morphology of isolated small arteries from patients with essential hypertension.
AB  - In this paper the morphological results obtained with isolated subcutaneous
      resistance arteries from patients with essential hypertension are reviewed. There
      is good agreement from these studies that the lumen diameter is decreased and the
      media thickness to lumen diameter ratio increased in patients with essential
      hypertension, which is consistent with data obtained from in vivo measurements of
      these variables using plethysmographic methods. On the other hand there is little
      or no increase in the media thickness. This suggests that an important means by
      which the morphological changes in hypertension are established is through a
      reorganization of the wall material around the lumen, a process known as
      "remodelling"; growth of smooth muscle may only have a minor role. In general,
      antihypertensive therapy increases the lumen diameter and decreases the media
      thickness to lumen diameter ratio; recent studies suggest that there may be drug
      specific effects on these variables.

PMID- 7582066
TI  - Effects of ACE inhibitors and calcium antagonists on progression of chronic renal
      disease.
AB  - The declining mortality due to coronary heart disease and stroke has been
      attributed in part to improved effectiveness and application of antihypertensive
      therapy and the successful identification and treatment of the population at
      risk. In striking contrast, end-stage renal disease (ESRD) attributed to
      hypertension has increased annually for the last decade and will probably worsen
      at least through the year 2000. Taken together, patients with diabetic
      nephropathy and patients with hypertensive renal disease account for the majority
      of new cases annually. The reasons for the striking dissociation between our
      success with coronary heart disease and stroke on the one hand and our inability
      to lessen the incidence of ESRD on the other remain to be clarified. Evidence
      reveals that all levels of untreated hypertension are associated with potentially
      declining renal function. Data from the Hypertension Detection and Follow-up
      Program and other studies suggest that antihypertensive treatment can prevent or
      retard development of progressive renal failure. Although the importance of blood
      pressure control is implicit, a theoretic framework based on data derived from
      experimental animal suggests that ACE-inhibitors and perhaps calcium antagonists
      may exert specific renoprotective effects beyond those achieved by blood pressure
      reduction per se. The results of recent long-term prospective studies are
      consistent with such a formulation. In view of the increasing importance of ACE
      inhibitors and calcium antagonists in the antihypertensive armamentarium,
      additional prospective randomized studies are required to delineate further the
      effects of these agents on the progression of chronic renal insufficiency.

PMID- 7582068
TI  - Cardiac hypertrophy and hypertension.
AB  - The epidemiology of left ventricular hypertrophy (LVH) in hypertension has been
      extensively studied and its importance as a cardiovascular risk factor is
      established. Significant advances in recent years have also occurred in
      pathophysiology, detection of LVH, and in management including regression of
      hypertrophy. Advances in pathophysiology have demonstrated that a number of
      trophic factors such as stretch, angiotensin II and stimulation of the
      sympathetic nervous system contribute towards the hypertrophy of the myocyte. In
      addition, it is important to emphasise factors such as aldosterone and
      angiotensin which contribute towards the proliferation of fibroblasts. The
      mechanisms involved in the increased mortality in patients with left ventricular
      hypertrophy remain to be determined, but myocardial ischaemia, left ventricular
      dysfunction and a propensity to ventricular arrhythmias have all been studied in
      detail. Echocardiography is a more reliable method for detecting LVH than ECG,
      but these investigations should be regarded as complementary rather than one
      being performed to the exclusion of the other. It remains unclear as to whether
      regression of LVH specifically contributes to a reduction in overall
      cardiovascular risk, but the key point seems to be optimal control of blood
      pressure, and only with further clinical trials will the exact impact of
      regression of LVH on morbidity and mortality be known.

PMID- 7582070
TI  - Salt intake as a determinant of cardiac hypertrophy.
AB  - Sodium homeostasis profoundly influences the cardiovascular system in
      normotensive and hypertensive subjects and is related to cardiovascular morbidity
      and mortality independently of other cardiovascular risk factors, including
      hypertension. Left ventricular hypertrophy has a variety of negative effects on
      myocardial structure and function and is a risk factor per se. Dietary salt
      intake either estimated by daily sodium excretion or calculated by the food
      consumed throughout 24 h has been repeatedly found to be a strong and, in
      particular, blood pressure-independent predictor of left ventricular posterior
      wall thickness and left ventricular mass. Dietary salt intake participates in the
      hypertrophic process via mechanisms not yet clearly defined. Experimental data
      and results of the TOMHS study further suggest that salt restriction reduces the
      degree of left ventricular hypertrophy.

PMID- 7582069
TI  - Cardiac hypertrophy and related growth processes: the role of insulin-like growth
      factor-I.
AB  - For the heart and resistance vessels in general, increases in pressure load
      represent a major local stimulus for structural adaptation by elevating the wall
      tension against which cardiac and vascular smooth muscle contract. Under such
      conditions the wall thickness of the left ventricle and of the resistance vessels
      will increase, keeping wall tension per unit muscle layer (wall stress) normal.
      Alternatively, chronic volume overload and enhanced cardiac filling will induce a
      structurally based widening of the ventricular lumen. This pattern is associated
      with a corresponding increase in myocardial mass, so that the wall thickness to
      internal radius ratio remains more or less constant. A number of extrinsic
      influences such as the sympathetic nervous system, hormonal factors and growth
      factors, may superimpose their effects to modulate the final "trophic influence"
      on the cardiovascular system. Hyperactivity of the renin-angiotensin system, the
      sympathetic nervous system and various growth factors, have all been suggested to
      initiate cardiovascular growth in a way that is load-independent. The mechanisms
      involved in the conversion of a mechanical hypertrophic stimulus into an actual
      increase in tissue mass are likely to involve many substances and enzyme systems,
      including transcription factors, enzymes such as ornithine decarboxylase and
      various growth factors. The presence of the insulin-like growth factor-I (IGF-I)
      in the heart and vessels suggests a paracrine/autocrine role for this potent
      growth factor in the regulation of cardiovascular growth. The relationships
      between ornithine decarboxylase, cardiovascular hypertrophy and IGF-I gene
      expression are also reviewed.

PMID- 7582071
TI  - Cardiac trophic stimuli and the transplanted heart.
AB  - Both hemodynamic and non-hemodynamic stimuli are recognized as regulators of
      cardiac growth. The chronic effects of an increase in systolic wall stress on
      left ventricular (LV) mass in the absence of cardiac sympathetic nerve activity
      can be assessed in human cardiac transplant recipients. Hypertension develops
      within several weeks/months after transplantation in patients treated with
      cyclosporine. Two longitudinal studies have shown that the absolute LV mass
      remains at control values despite an increase in both blood pressure and body
      weight. The chronic trophic effects of humoral stimuli on LV mass in the absence
      of hemodynamic load can be assessed following heterotopic cardiac transplantation
      into the abdomen of rats, with end to side aorto-aortic anastomosis between the
      donor and recipient aorta. The transplanted heart functions as a denervated "non
      working" Langendorff heart. In these animals, the transplanted heart atrophies by
      about 30-40% within 5-10 days. Although this atrophy may relate to hemodynamic
      unloading per se, chronic infusions of methoxamine or isoproterenol can prevent
      the atrophy. The hemodynamic unloading and/or sympathetic denervation appear to
      increase the sensitivity for these agonists. The transplanted heart thus offers a
      unique opportunity to study the interactions of hemodynamic and non-hemodynamic
      stimuli for cardiac growth.

PMID- 7582072
TI  - Steroids, hypertension and cardiac fibrosis.
AB  - Though we normally think of mineralocorticoid receptors as mediating aldosterone
      action on the kidney and other epithelia, the same receptors are found at
      comparable levels in non-epithelial tissues such as hippocampus and heart. In all
      tissues mineralocorticoid receptors have identical, high affinity for
      aldosterone, corticosterone and cortisol. In tissues such as the heart and
      hippocampus they are unprotected by the enzyme 11 beta hydroxysteroid
      dehydrogenase, which converts glucocorticoids to inactive 11-keto congeners; in
      such tissues mineralocorticoid receptors are thus overwhelmingly occupied by
      glucocorticoids, reflecting their much higher circulating levels. The epithelial
      effects of mineralocorticoid receptors and glucocorticoid receptors appear
      relatively uncomplicated, paralleling findings in cotransfection systems
      (corticosterone and cortisol, as well as aldosterone, are agonist in
      mineralocorticoid receptors; activated mineralocorticoid receptors and activated
      glucocorticoid receptors equivalently transactivate gene expression). In non
      epithelial tissues, most notably the brain, the actions (and possible
      interactions) of mineralocorticoid receptors and glucocorticoid receptors appear
      much more complex, and are yet to be established in detail. We have recently
      confirmed and extended the findings of Weber and his colleagues that
      administration of aldosterone or deoxycorticosterone to uninephrectomized rates
      drinking 1% NaCl solution for 8 weeks is followed by interstitial and
      perivascular cardiac fibrosis. Whether or not the effect of corticosteroids on
      cardiac fibrosis reflects direct actions on cardiac muscle, or other cellular
      constituents of the heart, there appears to be significant interplay between
      mineralocorticoid receptors and glucocorticoid receptors, and possible roles for
      agonist and antagonist occupancy of both receptor types.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7582073
TI  - Transforming growth factor-beta 1 and the development of vascular hypertrophy in
      hypertension.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine
      capable of regulating the growth and differentiation of many cell types, as well
      as regulating their environment in the blood vessel wall. Its production by
      endothelium and/or vascular smooth muscle is stimulated by biophysical forces,
      growth factors and also vasoconstrictors. In hypertension TGF-beta 1 gene
      transcription is most likely elevated by a combination of physical and chemical
      stimuli with the cytokine acting to increase the production of extracellular
      matrix proteins or to modulate smooth muscle cellular growth, producing
      hypertrophy, polyploidy or proliferation. With respect to the latter, TGF-beta 1
      potentiates the proliferative effects of many receptor tyrosine kinase-activating
      growth factors in vascular smooth muscle from SHR, but inhibits such
      proliferation in WKY smooth muscle. It also differentially affects collagen
      production by the two cell types. It is suggested that the augmented
      proliferative response in renal hypertensive SHR, compared to renal hypertensive
      WKY, is the consequence of these differential effects of TGF-beta 1 on smooth
      muscle cell proliferation. TGF-beta 1 is also likely to be a significant
      contributor to the development of vascular hypertrophy in genetic hypertension.

PMID- 7582074
TI  - Vascular remodeling in hypertension: role of autocrine-paracrine factors.
AB  - It has been postulated that changes in vessel structure have an important role in
      the pathogenesis of essential hypertension. Despite the potential pathogenetic
      importance of vascular remodeling, the molecular basis of this process remains
      poorly characterized. A rapidly emerging body of evidence indicates that many of
      the processes responsible for remodeling the vasculature are mediated by complex
      interactions between autocrine-paracrine factors generated within the vessel
      wall. Indeed, at the level of a single vessel the overall vessel structure
      appears to be determined by a yin-yang balance of stimulatory and inhibitory
      factors that module cell growth, death, migration and extracellular matrix
      composition. There is increasing evidence that factors that regulate vessel tone
      are also important determinants of vessel structure. This review focuses on
      angiotensin II as a paradigmatic vasoactive substance capable of mediating the
      process of vascular remodeling which is predominantly associated with vascular
      hypertrophy in hypertension. The pathogenetic and clinical implications of
      understanding these autocrine-paracrine systems are discussed.

PMID- 7582075
TI  - Cardiovascular Structure and Reactivity in Hypertension. Proceedings of a
      satellite symposium to the 15th meeting of the International Society of
      Hypertension. Melbourne, Australia, March 1994.

PMID- 7582076
TI  - Angiotensin II-mediated signal transduction events in vascular smooth muscle
      cells: kinases and phosphatases.
AB  - In this short review, the protein kinases and phosphatases that are involved in
      angiotensin II-mediated signal transduction in vascular smooth muscle cells are
      discussed. Reversible phosphorylation by the actions of kinases and phosphatases
      is a common signal transduction mechanism that many cell types utilize to
      stimulate cell growth. Besides its vasoconstrictor activity, angiotensin II
      stimulates hypertrophy of vascular smooth muscle cells and is involved in
      neointimal proliferation following balloon angioplasty. Understanding angiotensin
      II-stimulated kinases and phosphatases, as well as the crosstalk among
      phosphorylation pathways, may form the basis for the development of new
      therapeutic treatment of hypertension and/or restenosis.

PMID- 7582077
TI  - Cardiovascular hypertrophy and hypertension: causes and consequences.
AB  - In chronic hypertension, vascular resistance is raised and there is concentric
      left ventricular (LV) hypertrophy, at least in animal models. Together these
      changes enhance hemodynamic performance ("amplifier" properties) and help
      maintain elevated blood pressure (BP) and net microcirculatory exchange.
      Sometimes there is vascular "remodelling", with only luminal narrowing, but no
      net increase in medial mass. This can be related to non-uniform distribution of
      wall stress: when the amount of hypertrophy normalizes average wall stress, that
      on luminal side tends to be undercorrected accounting for preferential growth in
      that direction, whilst stress on the adventitial side is overcorrected, which
      results in a tendency to reabsorb material. In Goldblatt hypertension, about 20%
      of the rise in BP is due to the renal artery stenosis resistance, with the rest
      differing during the early and late phases: the early contribution is due to
      angiotensin II (AngII)-mediated systemic constriction and subtle fluid volume
      changes, whilst later on the cardiovascular amplifiers take over many of the
      actions of AngII. In SHR, trophic sympathetic nervous system actions are crucial
      for the rise in BP and development of structural changes and both contribute to
      the elevation of BP. Neonatal sympathectomy + prazosin treatment prevents
      hypertension and structural changes in SHR. Angiotensin converting enzyme (ACE)
      plays a similar role in cardiovascular development in SHR and Wistar Kyoto (WKY)
      rats. Prolonged administration of ACE inhibitors to SHR produces long term
      attenuation of hypertension because of an impaired capacity for cardiovascular
      development in adult animals. In human hypertension, long term treatment with
      common antihypertensive drugs is required to produce substantial regression of
      cardiovascular hypertrophy. Since it imposes marked non-uniformity on the
      distribution of capillary blood flow, with the potential for rarefaction and
      organ damage, therapy aimed at regression of hypertrophy is a worthwhile target.

PMID- 7582079
TI  - Gene expression and vascular smooth muscle cell phenotype.
AB  - Vascular smooth muscle cells (VSMCs) are involved in a number of vascular disease
      processes including hypertension and atherosclerosis. However, their role in the
      pathogenesis of vascular disease is largely undetermined. We and others have
      studied rat VSMCs in cell culture as a model for VSMC behaviour in vivo. In
      recent experiments we have applied molecular biological techniques to compare
      genes expressed by normal contractile VSMCs with those expressed by VSMCs which
      have undergone several passages in cell culture. Using differential screening of
      a cDNA library derived from cultured rat aortic VSMC RNA we identified seven
      genes which are preferentially expressed by contractile VSMCs; alpha-smooth
      muscle actin, gamma-smooth muscle actin, calponin, phospholamban, tropoelastin,
      SM22 alpha and CHIP28, and two which are preferentially expressed in passaged
      cells which have down-regulated their contractile proteins; osteopontin (OP) and
      matrix Gla protein (MGP). In situ hybridization studies have confirmed that
      calponin and SM22 alpha, are highly expressed by medial VSMCs in human coronary
      arteries with little or no expression in the atheromatous intima whilst the
      converse is true for OP and MGP. Studies by ourselves and others have confirmed
      that OP is a marker for proliferating rat VSMCs both in vitro and in vivo.
      However, the evidence that OP is expressed by proliferating human VSMCs is less
      convincing.

PMID- 7582078
TI  - Evidence in vivo for induction of cardiovascular growth processes by
      vasoconstrictor systems.
AB  - Greater smooth muscle growth is an important feature of the changes in blood
      vessel morphology in hypertension. The increase in vessel wall thickness: lumen
      ratio resulting from vascular hypertrophy impacts directly on total peripheral
      vascular resistance thereby influencing the severity of hypertension. The roles
      played by mechanical forces, vasoactive substances, growth factors and endocrine
      hormones in mediating hypertrophic vascular growth responses in vivo are
      currently under investigation. Here we review our current research aimed at: (a)
      defining the roles in vivo, of the renin-angiotensin system (RAS) and sympathetic
      nervous system (SNS), in the development of cardiovascular hypertrophy; (b)
      defining the importance of endogenous vasodilator systems, in particular, the
      ability of nitric oxide to inhibit trophic responses induced by the RAS and SNS
      and (c) examining whether trophic stimulation via the two neurohumoral systems as
      well as the antitrophic activity of the vasodilator systems is in part dependent
      on changes in blood pressure. In these studies the obligatory enzyme ornithine
      decarboxylase has proved to be a useful marker of ongoing hypertrophic
      cardiovascular growth.

PMID- 7582080
TI  - Pre-glomerular structural changes in the renal vasculature in hypertension.
AB  - This paper reviews the evidence for the occurrence of hypertrophy of the renal
      arterial vessels in experimental and human hypertension. In spontaneously
      hypertensive rats (SHR), the walls of the interlobar, arcuate and interlobular
      arteries appear to be hypertrophied in both the "pre-hypertensive phase" and in
      established hypertension. The lumen diameter of the afferent arteriole in SHR is
      reduced, but this is probably not due to wall hypertrophy. The renal arterial
      hypertrophy is not reversed by chronic angiotensin converting enzyme inhibition
      in SHR, in contrast to findings in other vascular beds. Renal arterial
      hypertrophy also occurs in other forms of hypertension including in the kidney
      contralateral to a renal artery stenosis, and in hypertension following sino
      aortic denervation. Whilst it is not possible to document changes in wall
      dimensions of intrarenal arteries during the development of human hypertension,
      renal haemodynamic abnormalities currently attributed to renal vasoconstriction
      in early human hypertension are also compatible with renal arterial hypertrophy.
      These abnormalities include increased resting renal vascular resistance and
      augmented renal vascular resistance responses to vasoconstrictor agents. It is
      argued that hypertrophy of renal vasculature to increase pre-glomerular
      resistance will have dual effects: it will increase total peripheral resistance
      (the kidneys account for about 20% of total peripheral resistance), and it will
      effect renal haemodynamics distally in a manner similar to narrowing of the main
      renal artery. It remains to be shown experimentally whether renal arterial
      hypertrophy could be the primary cause of some forms of hypertension.

PMID- 7582082
TI  - Enhancement of intrarenal angiotensin II levels in 2 kidney 1 clip and
      angiotensin II induced hypertension.
AB  - Previous studies have indicated that the hypertension that develops after
      unilateral arterial constriction (2 kidney, 1 clip) involves an active
      participation by the non-clipped contralateral kidney. Even though the non
      clipped kidney is not the initial causative factors, and despite the progressive
      renin depletion during the early weeks following clipping, the non-clipped kidney
      is highly responsive to angiotensin blockers. Furthermore, the non-clipped kidney
      has augmented tissue ANG II levels and ACE activity suggesting that some renin
      independent mechanism may be stimulating intrarenal ANG II formation. This model
      has been simulated by infusing ANG II at low subpressor doses (40 ng/min) to
      uninephrectomized rats for 14 days. With this model, plasma and renal renin
      levels are markedly suppressed; however, the renal ANG II levels are increased to
      levels above those that can be explained on the basis of circulating ANG II. In
      agreement with the responses observed in the non-clipped kidney of 2K1C rats,
      there is also an increased renal ACE activity. In contrast to the marked
      suppression of renin gene expression and renin activity, angiotensinogen gene
      expression is not suppressed. These results support the hypothesis that small
      elevations in circulating ANG II stimulate intrarenal ANG II production through a
      renin-independent mechanism.

PMID- 7582081
TI  - Renal neural mechanisms in salt-sensitive hypertension.
AB  - Genetic forms of salt (NaCl)-sensitive hypertension are characterized by
      increased renal sympathetic nerve activity responses to environmental stimuli.
      The increases in renal sympathetic nerve activity produce marked changes in renal
      function with renal vasoconstriction and sodium and water retention which can
      contribute to the initiation, development and maintenance of hypertension. In
      genetic forms of NaCl-sensitive hypertension, increased dietary NaCl intake
      produces alterations in norepinephrine kinetics with decreased concentrations of
      norepinephrine in regions of the anterior hypothalamus which are critical for the
      regulation of peripheral sympathetic nerve activity. This local central decrease
      in tonic alpha 2 adrenoceptor sympathoinhibitory input leads to increased
      peripheral (renal) sympathetic nerve activity and hypertension. Similarly, with
      increased dietary NaCl intake, patients with NaCl-sensitive hypertension develop
      increased arterial pressure, renal vasoconstriction, increased glomerular
      capillary pressure and increased urinary albumin excretion. Thus, increased
      dietary NaCl intake can, via central nervous system actions, produce increases in
      renal sympathetic nerve activity whose renal functional effects contribute to the
      pathophysiology of hypertension.

PMID- 7582083
TI  - Status of current therapies for hypertension.
AB  - Specific antihypertensive therapy has been in common clinical use for about four
      decades. During this relatively short period of time remarkable progress has been
      made in many regards. The value of lowering elevated arterial pressure has been
      documented in a number of intervention trials. Initially, such studies comprised
      patients with malignant hypertension only, but later large-scale studies have
      comprised patients with non-malignant forms of hypertension. At the same time
      numerous new pharmacological principles have been taken into clinical use in the
      treatment of hypertension. It is the purpose of this brief review to sum up some
      of the important steps that have been taken in this area during previous decades
      and to try to evaluate the status of current therapies for hypertension. Special
      emphasis will be given to some of the remaining issues and questions that are
      currently under investigation, such as the place of novel therapies, e.g. calcium
      antagonists and ACE-inhibitors, and the issue of the level to which blood
      pressure should be lowered in order to extract the maximum benefit of
      antihypertensive treatment. Some of the ongoing large-scale intervention trials
      in hypertension, e.g. the CAPPP Study, the NORDIL Study, the HOT Study and the
      STOP Hypertension-2 study, will be reviewed.

PMID- 7582084
TI  - Factors influencing the success of withdrawal of antihypertensive drug therapy.
AB  - We have reviewed the literature on the effect of withdrawal of antihypertensive
      therapy on return to hypertension. We also present our data from 83 patients in
      whom a 12-month follow-up period showed that 28% required re-institution of
      therapy within 10 weeks of withdrawal of medication, over half by 20 weeks, but a
      significant proportion (28%) stayed normotensive off therapy for a year. All
      patients had met the criteria for resumption of antihypertensive medication after
      2 years of therapy. We also demonstrated predictive effects of left ventricular
      hypertrophy and duration of therapy on rate of redevelopment of hypertension. Our
      study raises the possibility that echocardiography may indicate the likelihood of
      a rapid return to hypertension when drug therapy is ceased.

PMID- 7582086
TI  - Electrophysiology of the neurons in the area of the enkephalinergic magnocellular
      dorsal nucleus of the guinea-pig hypothalamus, studied by intracellular and whole
      cell recordings.
AB  - The electrophysiological characteristics of 103 hypothalamic neurons in the area
      of the guinea-pig enkephalinergic magnocellular dorsal nucleus were studied in a
      thick slice preparation with sharp microelectrodes (63 neurons) and patch
      pipettes for whole-cell recordings (40 neurons). Of the sampled cells, 79.6%
      displayed tetrodotoxin-resistant, calcium-dependent slow-depolarizing potentials
      when the membrane potential was hyperpolarized to approximately -70 mV (type I
      neurons). Half of them showed robust slow depolarizing potentials, generating
      bursts of fast action potentials. In the remaining neurons, the slow-depolarizing
      potentials did not cause burst-firing action potentials but triggered single
      action potentials. The other class of neurons (20.4% of the sample: type II
      neurons) did not exhibit calcium-dependent slow-depolarizing potentials. Resting
      potential, input resistance and the membrane time constant did not distinguish
      among the two classes of neurons. Current-voltage relationships were
      heterogeneous. A transient outward rectification was observed in the two classes.
      This was not totally blocked by 2 mM 4-aminopyridine but was abolished when using
      perfusion with cobalt instead of calcium. Input resistance and the time constant
      were higher when measured in the whole-cell mode but the other electrical
      parameters and the sampling of the recorded neurons were strikingly similar
      between the two methods of recording. Intracellular staining of 22 neurons
      retrogradely labelled from the lateral septum allowed confirmation of their
      location within the magnocellular dorsal nucleus. The study indicates that the
      electrical properties of these neurons did not differ from those of neurons found
      throughout the area explored. It also indicates the presence of distinct
      electrophysiological types of cells in the magnocellular dorsal nucleus, although
      the nucleus is composed of a single type of enkephalinergic neuron. It provides a
      basis for the study of the regulation of activity of the neurons at the origin of
      an enkephalinergic tractus which is involved in neuroendocrine,
      psychoneuroendocrine and immune processes.

PMID- 7582087
TI  - Involvement of serotonin in developmental plasticity of kitten visual cortex.
AB  - During a critical period of postnatal development, neuronal connections in the
      kitten visual cortex are susceptible to experience-dependent modifications. These
      modifications are facilitated by the neuromodulators noradrenaline and
      acetylcholine. To address the question of whether serotonin (5-hydroxytryptamine;
      5-HT), the other major neuromodulator in the cerebral cortex, also plays a role
      in developmental plasticity, we investigated whether interference with
      serotoninergic transmission in the kitten visual cortex affects ocular dominance
      (OD) plasticity. The serotonin neurotoxin 5,7-dihydroxytryptamine or the
      serotonin receptor blockers ketanserin and methysergide were infused into the
      visual cortex of kittens undergoing monocular deprivation. We found that both
      methods of disrupting serotoninergic transmission reduced OD plasticity. However,
      to be effective, the receptor blockers ketanserin and methysergide had to be
      applied in combination, suggesting that coactivation of serotonin receptor
      subtypes of both the 5-HT1 and 5-HT2 families have a permissive function in OD
      plasticity. Since activation of 5-HT2 receptors stimulates phosphoinositide
      hydrolysis, our data suggest that second messengers from the phospholipid pathway
      may play an important role in developmental plasticity of visual cortex.

PMID- 7582088
TI  - CO2 stimulation of the cornea: a comparison between human sensation and nerve
      activity in polymodal nociceptive afferents of the cat.
AB  - Excitation of nociceptors by low pH has been proposed as a cause of pain
      following tissue injury. Here we have studied the effect of pH reductions caused
      by application of CO2 pulses to the cornea on the activity of corneal afferent
      nerves of the cat and on the magnitude of pain sensations in humans. Single-unit
      activity was recorded from corneal afferent fibres in anaesthetized cats. The
      corneal receptive field of A-delta or C polymodal nociceptive units was exposed
      for 30 s to a gas mixture with different concentrations of CO2 in air (0, 35, 50,
      65, 80 and 98.5%). Responses to CO2 were evoked at a mean threshold concentration
      of 40 +/- 3% CO2. They consisted of a discharge of impulses that decayed
      gradually to a tonic level. In 15% of the units the initial burst was absent. The
      CO2 concentration and firing frequency data could be fitted to a power function
      with an exponent of 1.12. Pulses of CO2 were also applied to the cornea of 16
      human volunteers. Sensations experienced were measured by means of a visual
      analogue scale and a verbal descriptor scale. Flow was adjusted below the
      mechanical stimulation threshold (2.8 +/- 0.5 mg). When mixtures containing 10
      90% CO2 in 5% steps were applied as 3 s pulses, threshold sensation, described as
      a mild stinging pain, was evoked at 33.5 +/- 4.0% CO2. This sensation became
      overtly painful with higher CO2 concentrations (47.5 +/- 3.6% CO2). For the same
      subject the sensory threshold was remarkably constant, though it changed with
      longer exposure times. The relationship between CO2 concentration and magnitude
      of pain could be adjusted to a power function with a power exponent of 1.12.
      Curves of CO2 concentration versus neural discharges in the cat and versus
      psychophysical sensation in humans were very similar. These results show that
      corneal polymodal nociceptors respond to protons, and encode changes in CO2
      concentration presumably reflecting pH changes. The same stimulus evokes corneal
      pain sensations in humans, thus opening the possibility of using CO2 as an
      effective stimulus for corneal aesthesiometry.

PMID- 7582085
TI  - TrkA tyrosine residues involved in NGF-induced neurite outgrowth of PC12 cells.
AB  - The proto-oncogene product gp140prototrk (TrkA) is the receptor tyrosine kinase
      that mediates nerve growth factor-induced neuronal survival and differentiation.
      In receptor tyrosine kinases, specific intracellular tyrosine residues become
      phosphorylated after ligand binding and the phosphorylated tyrosines induce the
      cascade of signal transduction. Here we have identified intracellular tyrosine
      residues of TrkA involved in nerve growth factor-induced neurite outgrowth of
      PC12 cells, using site-directed mutagenesis and a PC12 cell line expressing very
      low levels of endogenous TrkA (PC12nnr5 cells). We analysed eight conserved
      intracellular tyrosine residues of TrkA while the three putative
      autophosphorylation sites conferring tyrosine kinase activity were left intact.
      Five tyrosine residues, Y499, Y643, Y704, Y760 and Y794, in rat TrkA were
      involved in nerve growth factor-induced neurite outgrowth. None of these
      tyrosines mediated the full activity of wild-type TrkA, and a pair of these
      tyrosines, Y760 and Y794, promoted neurite outgrowth in an additive manner. These
      data indicate that no single tyrosine is sufficient to induce complete neurite
      outgrowth but the five tyrosine residues Y499, Y643, Y704, Y760 and Y794
      cooperate to exhibit the full activity of wild-type TrkA.

PMID- 7582089
TI  - Failure of axon regeneration in postnatal rat entorhinohippocampal slice
      coculture is due to maturation of the axon, not that of the pathway or target.
AB  - Horizontal slices which included the entorhinal area in continuity with the
      hippocampus were taken from the ventral levels of the cerebral hemispheres of rat
      pups from two age groups, from the 6th to the 8th postnatal days ('young') and
      the 12th to the 15th days ('old'). The slices were divided into an entorhinal
      part and a hippocampal part (which consisted of the hippocampus proper, dentate
      gyrus and subiculum) by a knife cut passing through the deep white matter of the
      entorhinal area. The slices were recombined in their normal orientation by
      matching the cut edges in the following age combinations: young/young, old/old,
      young/old and old/young. After 14 days in culture, crystals of biocytin were
      placed on the superficial layers of the entorhinal area. In the young/young
      combination the same placement of biocytin simultaneously labelled projections
      passing in both directions across the interface, i.e. (i) orthograde transport of
      biocytin taken up by entorhinal projection neurons resulted in labelling of axons
      passing from the entorhinal area across the interface between the cocultures to
      reach the correct terminal zone in the outer molecular layer of the dentate
      gyrus, and (ii) retrograde transport of biocytin taken up by axons and their
      terminals in the entorhinal area labelled the slender subicular and adjacent
      hippocampal field CA1 pyramidal cells whose axons project to the entorhinal area.
      In the old/old cocultures there were no projections in either direction. In the
      mixed age combinations, young entorhinal cortical tissue projected correctly
      across the interface to old dentate gyrus, but old entorhinal tissue did not
      project to young dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582091
TI  - Response to novelty and its rapid habituation in locus coeruleus neurons of the
      freely exploring rat.
AB  - Activity of single units of the noradrenergic nucleus locus coeruleus was
      recorded in rats during active exploration of a novel environment. Novelty was
      controlled by the placement of objects in given holes in a hole board. The basic
      protocol included a habituation session in which the holes were empty and an
      object session in which a novel object was placed in one of the two holes. During
      the habituation session, when the whole environment was unfamiliar, there was a
      phasic response the first time the rat visited any hole, which habituated after
      one visit. During the second session, when one of the holes contained an object,
      the cell fired when the rat encountered the novel object. There was no response
      to empty holes in this session. The neuronal response was markedly diminished or
      entirely absent on the second and subsequent visits to object-containing holes,
      indicative of rapid habituation. In some rats it was possible to run a second
      object session, when a new object was introduced into a previously empty hole.
      Visits to this hole elicited a robust response, which again habituated after one
      single visit. The results show that the responses of locus coeruleus to novelty
      or change, which has been demonstrated in formal learning situations, occurs in
      freely behaving rats while they are learning about a new environment. Moreover,
      the response to novelty and change in the environment is short-lived, rapidly
      habituating after one or two encounters with the stimulus.

PMID- 7582090
TI  - 5'-nucleotidase activates and an inhibitory antibody prevents neuritic
      differentiation of PC12 cells.
AB  - Ecto-5'-nucleotidase catalyses the hydrolysis of AMP at the surface of a variety
      of cells whereas it is absent from others. In addition to its catalytic activity,
      a function in neural development and also its interaction with extracellular
      matrix proteins has been reported. In order to further elucidate the biological
      function of ecto-5'-nucleotidase we have investigated the effect of 5'
      nucleotidase on nerve growth factor-induced differentiation of PC12 cells.
      Furthermore, we compared the effect of an inhibitory versus a non-inhibitory
      monospecific antibody against the enzyme on neuritic differentiation and survival
      of PC12 cells that constitutively express the enzyme. When coverslips are coated
      with the soluble form of ecto-5'-nucleotidase in addition to collagen, there is a
      considerable increase in nerve growth factor-induced neurite length during the
      first 24 h of culture. Addition of an antibody to a culture medium that inhibits
      5'-nucleotidase activity to 33% of control values dramatically reduces the number
      of neurites per cell within 3 days of culture. The cells round up, cluster and
      eventually die. On the contrary, another antibody that had no significant effect
      on enzyme activity affected neither nerve growth factor-induced neurite formation
      nor survival of PC12 cells. Addition of adenosine (200 nM, 10 or 20 microM) to
      the culture medium did not influence PC12 cell differentiation. The effects
      induced by the inhibitory antibody could be only partially prevented by
      simultaneous application of adenosine. Our results suggest that 5'-nucleotidase
      is essential for nerve growth factor-induced neurite outgrowth and survival of
      PC12 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582092
TI  - Glycine- and GABA-activated currents in identified glial cells of the developing
      rat spinal cord slice.
AB  - In the neonatal rat spinal cord, four types of glial cells, namely astrocytes,
      oligodendrocytes and two types of precursor cells, can be distinguished based on
      their membrane current patterns and distinct morphological features. In the
      present study, we demonstrate that these cells respond to the inhibitory
      neurotransmitters glycine and GABA, as revealed with the whole-cell recording
      configuration of the patch-clamp technique. All astrocytes and glial precursor
      cells and a subpopulation of oligodendrocytes responded to glycine. The
      involvement of glycine receptors was inferred from the observation that the
      response was blocked by strychnine and that the induced current reversed close to
      the Cl- equilibrium potential. GABA induced large membrane currents in astrocytes
      and precursor cells while oligodendrocytes showed only small responses. The GABA
      activated current was due to the activation of GABAA receptors since muscimol
      mimicked and bicuculline blocked the response; moreover, the reversal potential
      was close to the Cl- equilibrium potential. Besides the increase in a Cl-
      conductance, GABAA receptor activation also induced a block of the resting K+
      conductance, as observed previously in Bergmann glial cells. Our experiments show
      that while glial GABAA receptors are found in many brain regions and the spinal
      cord, glial glycine receptors have so far been detected only in the spinal cord.
      The restricted coexpression of glial and neuronal glycine receptors in a defined
      central nervous system grey matter area implies that such glial receptors may be
      involved in synaptic transmission.

PMID- 7582093
TI  - Effects of nigrostriatal denervation and L-dopa therapy on the GABAergic neurons
      in the striatum in MPTP-treated monkeys and Parkinson's disease: an in situ
      hybridization study of GAD67 mRNA.
AB  - The effects of nigrostriatal denervation and L-dopa therapy on GABAergic neurons
      were analysed in patients with Parkinson's disease and in monkeys rendered
      parkinsonian by MPTP intoxication. The expression of the messenger RNA coding for
      the 67 kDa isoform of glutamic acid decarboxylase (GAD67 mRNA), studied by
      quantitative in situ hybridization, was used as an index of the GABAergic
      activity of the striatal neurons. A significant increase in GAD67 mRNA
      expression, generalized to all GABAergic neurons, was observed in MPTP-treated
      monkeys compared to control monkeys in the putamen and caudate nucleus (+44 and
      +67% respectively), but not in the ventral striatum. L-Dopa therapy significantly
      reduced GAD67 mRNA expression in the putamen and caudate nucleus to levels
      similar to those found in control monkeys. However, the return to normal of GAD67
      mRNA expression was not homogeneous across all neurons since it was followed by
      an increase of labelling in one subpopulation of GABAergic neurons and a decrease
      in another. These data suggest that in MPTP-treated monkeys the degeneration of
      nigrostriatal dopaminergic neurons results in a generalized increase in GABAergic
      activity in all the GABAergic neurons of the striatum, which is partially
      reversed by L-dopa therapy. As the expression of GAD67 mRNA is less intense in
      the ventral than in the dorsal striatum, this increase in striatal GABAergic
      activity may be related to the severity of nigrostriatal denervation. In
      parkinsonian patients who had been chronically treated with L-dopa, GAD67 mRNA
      expression was significantly decreased in all GABAergic neurons, in the caudate
      nucleus (by 44%), putamen (by 43.5%) and ventral striatum (by 26%). The opposite
      variation of GAD67 mRNA in patients with Parkinson's disease, compared with MPTP
      treated monkeys, might be explained by the combination of chronic nigrostriatal
      denervation and long-term L-dopa therapy.

PMID- 7582094
TI  - Pattern formation in the mammalian forebrain: striatal patch and matrix neurons
      intermix prior to compartment formation.
AB  - The striatum of the mammalian forebrain is divided into two compartments: the
      patches and the matrix. Neurons of the patch compartment in the rat striatum
      become postmitotic earlier in neurogenesis than neurons of the matrix
      compartment. The selective adhesion of patch neurons to one another has been
      suggested previously to be an important developmental mechanism of striatal
      compartmentation. We asked if the selective adhesion of patch neurons is
      expressed before or after the migration of the majority of the matrix neurons
      into the striatum. Patch neurons were labelled in vivo by a fluorescent
      retrograde tracer injected into the substantia nigra on embryonic day 19, which
      almost exclusively labelled patch neurons. Matrix neurons were labelled with a
      maternal injection of bromodeoxyuridine at embryonic day 18. When animals were
      killed at embryonic day 20, the majority of the retrogradely labelled patch
      neurons were intermixed with the bromodeoxyuridine-labelled matrix neurons,
      although there appeared to be clustering of some of the patch neurons. However,
      by postnatal day 2 there was a complete segregation of the clusters of the
      retrogradely labelled patch neurons from the bromodeoxyuridine-labelled matrix
      neurons in the striatum. This process was modelled in vitro. The patch and matrix
      compartments were labelled in vivo at embryonic day 13 and 18 respectively, with
      different birthdate markers ([3H]thymidine or bromodeoxyuridine). At embryonic
      day 20 the striatal tissue was removed, dissociated and reaggregated in
      suspension cultures. After 1 day in vitro, labelled patch and matrix neurons were
      randomly intermixed within the reaggregates. Examination of the cultures at 2.5
      and 4 days in vitro revealed clumping of the labelled patch neurons towards the
      centres of the reaggregates. Over this same period, the labelled matrix neurons
      did not clump and were dispersed towards the periphery of the reaggregates. The
      results suggest that patch neuron adhesiveness may appear relatively soon after
      these neurons become postmitotic, but that this adhesiveness is unable to
      overcome the initial force produced by the massive migration of matrix neurons
      into the striatum. We hypothesize that a migratory phase of embryonic striatal
      development exists, when fated patch and matrix neurons intermix. After this
      migratory phase, patch neuron adhesiveness can produce the mature segregation of
      the striatal compartments.

PMID- 7582095
TI  - Characterization of nerve growth factor (NGF) release from hippocampal neurons:
      evidence for a constitutive and an unconventional sodium-dependent regulated
      pathway.
AB  - We investigated the mechanism of neuronal nerve growth factor (NGF) release with
      regard to the potential function of NGF as a mediator of neuronal plasticity in
      the CNS. The analysis was performed in hippocampal slices and in primary cultures
      of hippocampal neurons, transiently transfected with an NGF cDNA construct to
      increase the level of NGF expression. In both systems there was activity
      dependent NGF release initiated by high potassium (KCl), veratridine, glutamate
      or carbachol. Replacement of 90% of sodium in the medium with N-methyl-glucamine
      strongly reduced this release. The KCl- and veratridine-initiated NGF release was
      suppressed by tetrodotoxin; release by glutamate was less sensitive to
      tetrodotoxin but was sodium-dependent. The glutamate effect could be inhibited by
      GYKI52644, an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid receptors, but not by MK-801, an antagonist of NMDA receptors. The activity
      dependent release of NGF did not depend on extracellular Ca2+, but was sensitive
      to the intracellular Ca2+ chelator bis-(o-aminophenoxy)-ethane-N,N,N',N'
      tetraacetic acid tetra(acetoxymethyl)-ester, and to depletion of intracellular
      calcium stores. Conversely, mobilization of Ca2+ from intracellular stores with
      caffeine and thapsigargin mimicked the effect of depolarization. Basal NGF
      release could be reduced by either temperature block (15 degrees C) or
      tetrodotoxin to approximately 50%. The combination of both treatments reduced NGF
      release to below the detection limit, suggesting that basal release has
      constitutive and regulated components, the latter presumably resulting from
      spontaneous activity of interconnected neurons.

PMID- 7582096
TI  - Desensitization of AMPA receptors limits the amplitude of EPSPs and the
      excitability of motoneurons of the rat isolated spinal cord.
AB  - Intracellular recording was used to study the effect of cyclothiazide, a
      selective blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptor desensitization, on lumbar motoneurons of the rat isolated spinal cord.
      Cyclothiazide (25 microM) enhanced the responses to AMPA in a tetrodotoxin
      insensitive fashion, without affecting those produced by N-methyl-D-aspartate or
      gamma-aminobutyric acid. Excitatory postsynaptic potentials (EPSPs) evoked by
      dorsal root stimulation were strongly potentiated in amplitude while paired-pulse
      depression (produced by applying pairs of pulses at 2 s interval) of the EPSP was
      decreased. In the presence of cyclothiazide the frequency of spontaneous synaptic
      events was greatly increased and network-driven bursting activity developed with
      eventual loss of electrical excitability. The present results suggest that
      pharmacological block of AMPA receptor desensitization led to strong excitation
      of motoneurons and indicate a physiological role of desensitization in protecting
      these nerve cells from overactivity.

PMID- 7582097
TI  - Cellular and subcellular distribution of NMDAR1 splice variant mRNA in the rat
      lumbar spinal cord.
AB  - The regional distribution of alternatively spliced messenger RNA encoding the N
      methyl-D-aspartate (NMDA) receptor R1 subunit (NMDAR1) variants was examined by
      in situ hybridization in the rat lumbar spinal cord. Splice-specific
      oligonucleotide probes [recognizing full-length mRNA (NMDAR1-1), deletion exon 21
      (NMDAR1-2), deletion exon 22 (NMDAR1-3), combined deletion exons 21 and 22
      (NMDAR1-4) and mRNA which lacks (NMDAR1-a) or contains exon 5 (NMDAR1-b)]
      detected marked differences in abundance and distribution of N- and C-terminal
      spliced variants. The NMDAR1-a, NMDAR1-2 and NMDAR1-4 mRNAs were evenly
      distributed throughout all laminae of the dorsal and ventral horns. In the
      superficial dorsal horn NMDAR1-b mRNA was preferentially detected in laminae II
      inner and III, while NMDAR1-1 mRNA was restricted to laminae I to III. Large
      neurons in laminae IV and V contained mainly NMDAR1-a, NMDAR1-2 and NMDAR1-4
      mRNAs and occasionally NMDAR1-b. The NMDAR1-3 variant was only detected in very
      low abundance, being restricted to occasional cells in lamina I and II. In the
      ventral horn, motor neurons showed strong signals for NMDAR1-a, NMDAR1-b, NMDAR1
      2 and NMDAR1-4 mRNAs. Serial sectioning through large motor neurons permitted the
      detection of multiple splice variants in single neurons. Analysis of the
      subcellular distribution of the mRNAs revealed that the NMDAR1-1 mRNA was almost
      exclusively found in the cell nucleus, NMDAR1-a mRNA was largely in the
      cytoplasm, while all other splice variants showed a homogeneous distribution
      between nucleus and cytoplasm. Comparison of the in situ hybridization images
      with functional analyses of heteromeric recombinant receptors will be necessary
      to ascertain whether splice variants of the NMDAR1 receptor subunit can account
      for some of the known electrophysiological properties of spinal cord neurons
      under physiological and pathophysiological conditions.

PMID- 7582099
TI  - Role of Bcl-2 in the brain-derived neurotrophic factor survival response.
AB  - Developing neurons die if they fail to obtain an adequate supply of neurotrophins
      from their targets but how neurotrophins suppress cell death is not known.
      Although over-expression of exogenous Bcl-2 can prevent the death of cultured
      neurons deprived of members of the nerve growth factor family of neurotrophins it
      is not known if this effect is physiologically relevant. To determine if Bcl-2
      participates in the neurotrophin survival response we used antisense bcl-2 RNA to
      inhibit endogenous Bcl-2 expression. Here we show that brain-derived neurotrophic
      factor (BDNF)-dependent neurons are killed by antisense bcl-2 RNA in the presence
      of BDNF. However, when these neurons were supported with ciliary neurotrophic
      factor (CNTF) their survival was not affected by antisense bcl-2 RNA. Likewise,
      the survival of CNTF-dependent ciliary neurons was not affected by antisense bcl
      2 RNA. Our findings suggest that Bcl-2 is required for the BDNF survival response
      and that alternative, Bcl-2-independent survival mechanisms operate in sensory
      and parasympathetic neurons exposed to CNTF.

PMID- 7582100
TI  - Epileptiform activity in the guinea-pig neocortical slice spreads preferentially
      along supragranular layers--recordings with voltage-sensitive dyes.
AB  - The spread of epileptiform activity was monitored in guinea-pig neocortical
      slices by the use of a voltage-sensitive dye (RH795) and a fast optical recording
      technique. Epileptiform activity induced by bicuculline methiodide (10-20 microM)
      and single-pulse stimulation spread from the stimulation site in layer I or in
      the white matter across most of the slice. Different lesions were made in the
      slice in order to specify the neuronal connections used for spread in the
      horizontal direction. In the slice, intracortical connections are necessary for
      the spread of epileptiform activity, as shown by vertical cuts through all
      cortical layers but sparing the white matter. Horizontal connections were
      interrupted by cuts parallel to the axis of pyramidal neurons through either
      supragranular or infragranular layers. Vertical connections were interrupted by
      cuts perpendicular to the axis of pyramidal neurons separating supragranular and
      infragranular layers. Spread of epileptiform activity in the horizontal direction
      was not hindered by horizontal cuts. Vertical cuts through infragranular layers
      also did not hinder the spread of epileptiform activity. In contrast, vertical
      cuts through supragranular layers either abolished completely (nine slices) or
      delayed significantly (ten slices) the spread of epileptiform activity. The mean
      delay at the supragranular lesion was 44 ms in layer III and 30 ms in layer V; at
      the infragranular lesion the mean delay was 2 ms in layer III and 6 ms in layer
      V. Also, with horizontal cuts, in three out of five slices the velocity of spread
      was significantly lower in infragranular as compared to supragranular layers. It
      is concluded that both supra- and infragranular layers if isolated possess the
      ability to initiate and propagate epileptiform activity independently. However,
      in the intact slice the influence of the supragranular networks on initiation and
      propagation of epileptiform activity appears to dominate.

PMID- 7582101
TI  - Gamma-range activity evoked by coherent visual stimuli in humans.
AB  - We tested the hypothesis of a role of gamma-range synchronized oscillatory
      activity in visual feature binding by recording evoked potentials from 12
      subjects to three stimuli: two coherent ones (a Kanizsa triangle and a real
      triangle) and a non-coherent one (a Kanizsa triangle in which the inducing disks
      had been rotated so that no triangle could be perceived). The evoked potentials
      were analysed by convoluting the signal for each subject and each stimulation
      type by Gabor wavelets centred from 28 up to 46 Hz, providing a continuous
      measure of frequency-specific power over time. A first peak of activity was found
      around 38 Hz and 100 ms with a maximum at electrode Cz in each experimental
      condition. A second peak of activity occurred around 30 Hz and 230 ms, with a
      maximum at O1 in response to the real triangle and a maximum at Cz in the case of
      the illusory triangle. At 100 ms we did not find any variations of the gamma-band
      component of the evoked potential with stimulation type, but the power of the 30
      Hz component of the evoked potential between 210 and 290 ms differed from noise
      only in the case of a coherent triangle, no matter whether real or illusory. We
      thus found a 30 Hz component whose power correlates with stimulus coherency,
      which supports the hypothesis of a functional role of high-frequency
      synchronization in feature binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582102
TI  - Decrease of zif-268 and c-fos and increase of c-jun mRNA in the cat areas 17, 18
      and 19 following complete visual deafferentation.
AB  - We used in situ hybridization to investigate the effect of complete visual
      deafferentation on immediate early gene expression in adult cat visual cortex.
      Deafferentation was obtained by unilateral section of the optic tract and
      sections of both the corpus callosum and anterior commissure. In this model, one
      hemisphere served as control for the other within the same animal. A decrease in
      zinc finger protein (zif)-268 and c-fos mRNA was observed in the superficial and
      deep layers of areas 17 and 18, and all layers of area 19 in the deafferented
      hemisphere. This decrease, present 3 days after surgery, was maximal after 30
      days. An increase of c-jun mRNA was observed in the deep layers of areas 17, 18
      and 19 in the deafferented hemisphere 3, 10 and 30 days after surgery. These
      results suggest that visual input activates zif-268 and c-fos expression and
      tonically depresses c-jun expression in the primary visual complex yielding
      similar levels of c-jun and c-fos expression in normal conditions.

PMID- 7582098
TI  - Lines of murine oligodendroglial precursor cells immortalized by an activated neu
      tyrosine kinase show distinct degrees of interaction with axons in vitro and in
      vivo.
AB  - Replication-defective retroviruses expressing the t-neu oncogene, or a hybrid
      protein with the neu tyrosine kinase linked to the external region of the human
      epidermal growth factor receptor (egfr-neu), were used to establish lines of
      murine oligodendroglial precursor cells. Differentiation of the t-neu lines into
      myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by
      dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro
      upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons
      expressed mitogens for the cell lines. Upon transplantation into demyelinated
      lesions, t-neu line cells engaged with the demyelinated axons whereas the egfr
      neu line cells differentiated further and ensheathed the axons. These cell lines
      thus interact with neurons in vitro and in vivo and can be used as tools to
      define the molecules involved in different stages of neuron-glia interaction.

PMID- 7582103
TI  - Involvement of AMPA receptors in maintenance of memory for a passive avoidance
      task in day-old domestic chicks (Gallus domesticus).
AB  - Day-old chicks (Gallus domesticus) were trained on a one-trial passive avoidance
      task where the aversive stimulus was an unpleasant tasting substance, methyl
      anthranilate. Chicks were killed 6.5 h after training. The kinetic parameters of
      [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding
      were determined using quantitative receptor autoradiography and Scatchard
      analyses in 15 discrete forebrain regions of trained and control (water-trained)
      chicks, revealing two components of binding in each. KD values showed some
      regional variation, but were 22.2 +/- 1.1 nmol l-1 for the high-affinity
      component and 685 +/- 25 nmol l-1 for the low-affinity component of binding to
      whole forebrain sections from control chicks. Analyses also revealed that Hill
      coefficients were significantly less than 1 in all regions measured. A
      significant decrease in KD for the low-affinity component occurred bilaterally in
      the intermediate and medial hyperstriatum ventrale (IMHV; left, 34.8%; right,
      33.3%), a region that has previously been shown to be implicated in the processes
      of memory formation, following passive avoidance training. A significant decrease
      in KD for the high-affinity component occurred in the right palaeostriatum
      augmentatum (19.5%). Significant decreases in Bmax accompanied the KD alterations
      in both cases. Additionally, bilateral intracerebral injections (administered 4.5
      5.5 h after training) into the IMHV of 500 nmol l-1 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX), a selective antagonist of non-NMDA glutamate receptors
      (particularly AMPA receptors), resulted in amnesia for one-trial passive
      avoidance training in day-old chicks tested 6.5 h after training.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582104
TI  - Ultrastructural changes in the hydropic cochlea of the guinea-pig.
AB  - Transmission electron microscopy of the cochlear organ of Corti in experimental
      endolymphatic hydrops revealed two principal features. Starting 1 month after
      induction of hydrops, osmiophilic inclusions thought to represent lipofuscin
      accumulation were frequently observed in the subcuticular cytoplasm of the outer
      hair cells along the length of the cochlea. Starting 3 months after induction of
      hydrops the efferent terminals on the outer hair cells appeared to be vacuolated.
      These data suggest that oxidative insult is likely to contribute to the pathology
      associated with endolymphatic hydrops and thus that free radical scavengers might
      be useful in the treatment of Meniere's disease patients. In addition the early
      modification of the efferent innervation of the hydropic cochlea might underlie
      the known hypersensitivity to various insults, including noise stimulation,
      glycerol administration and hypoxia.

PMID- 7582105
TI  - Polymer encapsulated cell lines genetically engineered to release ciliary
      neurotrophic factor can slow down progressive motor neuronopathy in the mouse.
AB  - Ciliary neurotrophic factor (CNTF) has recently generated great interest due to
      its potential as a therapeutic agent for the treatment of human neurodegenerative
      diseases such as amyotrophic lateral sclerosis (ALS). Because the systemic half
      life of CNTF is only in the order of a few minutes, continuous delivery of this
      trophic factor could be attractive or even necessary in the therapy of these
      diseases. One promising technique involves the polymer encapsulation of cells
      which have been genetically modified to secrete neurotrophic factors. The polymer
      capsules can be implanted into animals and effect the slow release of the protein
      for several months. The encapsulation technique immuno-isolates the foreign cells
      from host immune cells and at the same time prevents tumour formation by the
      transplanted cells. In this study, we have used progressive motoneuronopathy
      (pmn) mice to determine the extent to which encapsulated cell lines secreting
      CNTF could alter the course of the disease. pmn/pmn homozygotes present severe
      loss of myelinated motor fibres and a significant reduction of facial motoneuron
      cell bodies. The mice develop weakness of the hindlimbs and die during the sixth
      week after birth. We found that CNTF delayed the disease progression by
      increasing the survival time by 40% and by improving motor function as assessed
      by three behavioural tests. Moreover, histological counts of the phrenic nerve
      myelinated axons and facial nucleus motoneurons indicated a significant reduction
      of motoneuron loss. These results suggest that polymer-encapsulated cells
      releasing neurotrophic factors may provide a potential delivery system for
      treating neurodegenerative diseases such as ALS.

PMID- 7582106
TI  - Subcellular localization of the GABAA receptor gamma 2 subunit in the rat spinal
      cord.
AB  - The fine subcellular organization of the GABAA receptor complex in the adult rat
      spinal ventral horn was analysed by immunocytochemistry using a specific
      polyclonal antiserum raised against the gamma 2 subunit. This subunit confers
      benzodiazepine sensitivity on the chloride channel of the GABAA receptor. With
      both fluorescent and peroxidase staining, the immunoreactivity was mainly
      observed in the grey matter and more specifically in the dorsal and ventral horns
      on medium and large neurons. A high number of immunostained somata were clustered
      in regions corresponding to motor nuclei. On the neuronal surface, labelling
      appeared as fluorescent dots over the more diffuse staining that was present on
      the soma and proximal part of dendrites. At the ultrastructural level, peroxidase
      end product was in most cases associated with the internal side of postsynaptic
      differentiations facing terminal boutons enriched with pleiomorphic small clear
      vesicles. The positively stained synapses were encountered on proximal dendrites
      of neurons and throughout the neuropil of the ventral horn (layers VII-IX). An
      immunoreactivity on the postsynaptic membrane was occasionally found to decorate
      large pieces of membrane not directly apposed to presynaptic active zones. In
      addition, presynaptic labelling was observed at axoaxonic contacts and at
      extrasynaptic sites on membranes within boutons, sometimes themselves apposed to
      gamma 2 immunoreactivity. Finally, we also observed gamma 2 immunoreactivity at
      the cytosolic face of the plasma membrane of some glial elements. These results
      give morphological evidence for the involvement of GABAA receptors in both post-
      and presynaptic inhibition in the rat spinal ventral horn. The presence of gamma
      2 subunit immunoreactivity at these different synaptic contacts suggests that the
      two types of inhibition can be modulated by benzodiazepine drugs. The findings
      also provide anatomical evidence for the possible regulation of GABA release
      through an autoreceptor, and for GABAergic communication between neuronal and
      glial components.

PMID- 7582107
TI  - HIV-1 gp120 glycoprotein induces [Ca2+]i responses not only in type-2 but also
      type-1 astrocytes and oligodendrocytes of the rat cerebellum.
AB  - Cultures of cerebellar cortex cells were exposed to the HIV-1 envelope
      glycoprotein, gp120, and investigated for cytosolic Ca2+ ion concentration
      ([Ca2+]i) changes by the fura-2 ratio videoimaging technique while bathed in
      complete, Na(+)-free or Mg(2+)-free Krebs-Ringer media. At the end of the [Ca2+]i
      experiments the cells were fixed and immunoidentified through the revelation of
      markers specific for neurons (microtubule associated protein-2), type-2 (A2B5) or
      all (glial fibrillary acidic protein) astrocytes, oligodendrocytes
      (galactocerebroside) or microglia (F4/80 antibody). In complete medium, rapid
      biphasic (spike-plateau) responses induced by gp120 (0.1-1 nM) were observed in a
      subpopulation of type-2 astrocytes. In addition, slow but progressive responses
      were observed in other type-2 cells and oligodendrocytes, whereas type-1
      astrocytes showed small responses, if any, and granule neurons did not respond at
      all. Use of Na(+)-free medium (a condition that blocked another gp120-induced
      response, cytosolic alkalinization) resulted in an increase in [Ca2+]i response
      that was appreciable not only in type-2 but also in most type-1 astrocytes,
      possibly because of the inhibition of the Na+/Ca2+ exchanger and the ensuing
      decrease in Ca2+ extrusion. Granule neurons, including those in direct contact
      with responsive astrocytes, remained unresponsive, even when the experiments were
      carried out in Mg(2+)-free medium supplemented with glycine, a condition that
      favors activation of the glutamatergic N-methyl-D-aspartate (NMDA)
      receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582109
TI  - Exposure to gp120 of HIV-1 induces an increased release of arachidonic acid in
      rat primary neuronal cell culture followed by NMDA receptor-mediated
      neurotoxicity.
AB  - After incubation of highly enriched neurons from rat cerebral cortex with the HIV
      1 coat protein gp120 for 18 h, cells showed fragmentation of DNA at
      internucleosomal linkers followed by NMDA receptor-mediated neurotoxicity. We
      report that in response to exposure to gp120 cells react with an increased
      release of arachidonic acid (AA) via activation of phospholipase A2. This process
      was not inhibited by NMDA receptor antagonists. To investigate the role of AA on
      the sensitivity of the NMDA receptor towards its agonist, low concentrations of
      NMDA were co-administered with AA. This condition enhanced the NMDA-mediated
      cytotoxicity. Administration of mepacrine reduced cytotoxicity caused by gp120.
      We conclude that gp120 causes an activation of phospholipase A2, resulting in the
      increased release of AA, which may in turn sensitize the NMDA receptor.

PMID- 7582108
TI  - Regional distribution and developmental variation of the glycine transporters
      GLYT1 and GLYT2 in the rat CNS.
AB  - The high-affinity glycine transporter in neurons and glial cells is the primary
      means of inactivating synaptic glycine. Previous molecular cloning studies have
      indicated heterogeneity of glycine transporters in the CNS. Here the distribution
      of glycine transporter GLYT1 and GLYT2 transcripts and proteins in different
      regions and developmental stages of the rat brain were analysed by Northern,
      Western and in situ hybridization techniques. Sequence-specific riboprobes and
      two specific antibodies raised against fusion proteins were used, containing
      either 76 or 193 amino acids of the C or N terminus of the GLYT1 and GLYT2
      transporters respectively. High levels of GLYT1 transcripts were found in the
      spinal cord, brainstem and cerebellum, and moderate levels in forebrain regions
      such as the cortex or hippocampus. GLYT2 transcripts are restricted to the spinal
      cord, brainstem and cerebellum. The onset of both GLYT1 and GLYT2 expression in
      the brainstem occurred in late fetal life, and full expression of these proteins
      was observed before weaning. There was a stepwise increase in the levels of mRNA
      and protein for these two transporters, reaching a maximum by the second
      postnatal week, followed by a slight decrease until adult values were reached by
      the fourth postnatal week. These data reveal interesting parallelism between the
      distribution of different glycine transporters and glycine receptor subunits, and
      suggest discrete roles for distinct glycine transporters.

PMID- 7582110
TI  - Inhibitors of cyclooxygenases produce amnesia for a passive avoidance task in the
      chick.
AB  - Arachidonic acid is a putative messenger in synaptic transmission which
      presumably plays a role in learning and memory. Previous experiments showed that
      inhibitors of phospholipase A2-dependent release of arachidonic acid cause
      amnesia in a one-trial passive avoidance task in the chick. To test if
      arachidonic acid is metabolized to other messengers, the effects of inhibitors of
      enzymes which metabolize arachidonic acid were tested in the same task. The
      cyclooxygenase inhibitors indomethacin, naproxen and ibuprofen caused amnestic
      effects at all concentrations tested when injected intracerebrally before
      training. Injections were 5 microliters of 5-20 mmolar solutions per hemisphere.
      The onset of amnestic effects was always 2 h after training, independently of
      drug type, concentration, and injection time before training. The delay of 2 h
      after training suggests that the drugs prevent induction of cyclooxygenase
      synthesis. Post-training injections had no effect. Control tests showed little
      effect of the drugs on motor control and motivation. Caffeic acid and esculetin,
      inhibitors of lipoxygenases, and sodium furegrelate, a thromboxane synthase
      inhibitor, had no effect on performance of chicks in the task at all
      concentrations or time points tested. The results indicate that cyclooxygenase
      products, but not lipoxygenase or thromboxane synthase products, play a role in
      memory consolidation in the chick when learning this task.

PMID- 7582112
TI  - Differential expression patterns of five acetylcholine receptor subunit genes in
      rat muscle during development.
AB  - The spatial and temporal expression patterns of five genes which encode the alpha
      , beta-, gamma-, delta- and epsilon-subunits of the nicotinic acetylcholine
      receptor in skeletal muscle were followed during development in the rat by in
      situ hybridization analysis. Three major developmental phases, characterized by
      specific expression patterns, could be distinguished. (i) During myogenic
      differentiation alpha-, beta-, gamma- and delta-subunit genes are activated and
      transcripts are expressed in muscle precursor cells at embryonic day 12 (E12) and
      during subsequent cell fusion. (ii) Following innervation of myotubes at
      approximately E15-E17 the mRNA of the alpha-, beta-, gamma- and delta-subunit
      genes accumulate in synaptic and decrease in extrasynaptic fibre regions during
      early synaptogenesis. The mRNA of the epsilon-subunit gene becomes detectable
      first in subsynaptic nuclei 2-3 days after innervation has occurred. (iii) During
      postnatal development alpha-, beta- and delta- subunit transcript levels are
      reduced predominantly in extrasynaptic fibre segments and show significant
      differences in distribution depending on the muscle subtype whereas the gamma
      subunit mRNA disappears completely within the first postnatal week in all
      muscles. In contrast, the epsilon-subunit gene is transcribed only in subsynaptic
      myonuclei throughout development and in the adult muscle.

PMID- 7582111
TI  - Expression of c-Jun, Jun B, Jun D and cAMP response element binding protein by
      Schwann cells and their precursors in vivo and in vitro.
AB  - In order to identify the transcription factors that may be involved in the
      development and differentiation of rat Schwann cells we examined the expression
      of c-Jun, Jun B, Jun D and the cAMP response element binding protein (CREB) in
      vivo and in vitro. We found that CREB was expressed at high levels throughout
      nerve development by both Schwann cells and their precursors. Jun family members,
      on the other hand, were expressed only at low levels in a few nuclei of the
      developing nerve. After sciatic nerve transection, however, c-Jun levels were
      rapidly up-regulated in many Schwann cells of the distal stump but CREB, Jun B
      and Jun D levels were not affected. When nerve contact was resumed after crush
      injury c-Jun levels returned to control values. Interestingly, unlike the
      situation in vivo, when Schwann cells were removed from the nerve and cultured,
      levels of all three Jun family members were rapidly up-regulated. This also
      occurred in Schwann cell precursors. In other experiments we found that Schwann
      cell c-Jun, but not Jun B or Jun D, expression was down-regulated by the
      adenylate cyclase activator, forskolin. In addition, we show that the forskolin
      induced down-regulation of c-Jun is not necessary for Schwann cell proliferation
      or myelination to occur.

PMID- 7582113
TI  - Calmodulin and in vitro regenerating frog sciatic nerves: release and
      extracellular effects.
AB  - Although calmodulin (CaM) is commonly considered to be an intracellular protein,
      it has been suggested lately that it is released and exerts functions
      extracellularly. In the present investigation this was studied in in vitro
      regenerating adult frog (Rana temporaria) sciatic nerves. Using a multi
      compartment incubation chamber, the non-neuronal cells in the outgrowth region of
      such nerves were radiolabelled with amino acid precursors. Based on immunological
      criteria, these cells were shown to release CaM. When the nerves were treated
      with CaM, both the outgrowth of sensory axons and the injury-induced
      proliferation of non-neuronal cells were partially inhibited. The inhibitory
      effects occurred even when the incubation medium contained as little as 30 pM
      CaM. Furthermore, treatment with anti-CaM antibodies resulted in reduced
      outgrowth, which suggested that during normal conditions extracellular CaM is
      kept at an optimal concentration. Finally, conditioned medium was found to
      contain several CaM-binding proteins. The present findings may reflect an earlier
      unknown function of extracellular CaM in controlling various growth mechanisms in
      integrated tissues.

PMID- 7582114
TI  - Physiological and morphological heterogeneity of dentate gyrus-hilus interneurons
      in the gerbil hippocampus in vivo.
AB  - A variety of morphological types of dentate gyrus/hilus interneurons have been
      described, but little is known about their corresponding physiological
      characteristics. To address this issue, intracellular responses to current
      injection and perforant path stimulation were obtained from putative dentate
      interneurons in anaesthetized adult gerbils. Our sample of interneurons showed
      heterogeneity in their intrinsic physiological characteristics and spike
      thresholds to perforant path stimulation, suggesting the existence of distinct
      physiologically-defined classes. 'Fast-spiking' interneurons had a low threshold
      to perforant path stimulation, whereas 'slow-spiking' interneurons responded with
      predominantly inhibitory potentials. In several cases, cells were intracellularly
      labelled with biocytin for visualization. Interneurons with different
      physiological traits had distinct morphological features. These results confirm
      that, as in hippocampus proper, morphologically identifiable interneurons in the
      dentate hilus show electrophysiological features that are likely to reflect
      functionally specific roles in informational processing.

PMID- 7582116
TI  - Connections of the lateral reticular nucleus to the lateral vestibular nucleus in
      the rat. An anterograde tracing study with Phaseolus vulgaris leucoagglutinin.
AB  - Efferent projections from the lateral reticular nucleus in the rat were
      investigated with anterograde transport of Phaseolus vulgaris leucoagglutinin.
      Besides the well known mossy fibre connections to the cerebellar cortex and
      collaterals to the cerebellar nuclei, a substantial bilateral projection to the
      lateral vestibular nucleus was found. Terminal arborizations found within this
      nucleus appeared to detach from the reticulocerebellar fibres in the cerebellar
      white matter and enter the lateral vestibular nucleus from dorsally. This
      projection may have functional relevance for the control, by ascending spinal
      pathways, of the descending lateral vestibulospinal tract.

PMID- 7582115
TI  - Truncated and catalytic isoforms of trkB are co-expressed in neurons of rat and
      mouse CNS.
AB  - Localization of mRNA encoding trkB indicates that two truncated isoforms of trkB,
      T1trkB and T2trkB, are differentially distributed in the rodent nervous system,
      and that each of these transcripts is co-expressed with catalytic trkB (TK+trkB)
      in adult motor neurons. In contrast to the prominent expression of T1trkB by non
      neuronal cells, T2trkB expression appeared to be restricted to neurons and
      demonstrated significant overlap with the pattern of TK+trkB distribution. In
      developing spinal cord ventral horn, an age-related increase in hybridization was
      observed for truncated isoforms. These findings suggest that truncated trkB may
      modulate neuronal responses to neurotrophins which act via trkB.

PMID- 7582117
TI  - Flip and Flop variants of AMPA receptors in the rat lumbar spinal cord.
AB  - The expression of eight messenger RNA splice forms encoding the Flip and Flop
      variants of AMPA receptor subunits GluR-A to -D in the rat lumbar spinal cord was
      examined by in situ hybridization using specific oligonucleotides. In the dorsal
      horn (laminae I, II and III) the predominant mRNA was GluR-B Flip. Much lower
      levels of GluR-A Flip were found in lamina I and in superficial parts of lamina
      II outer. In the ventral horn, motor neurons expressed mainly GluR-B Flip, GluR-C
      Flip and Flop, and GluR-D Flip. Serial sectioning through large motor neurons
      indicated that a given cell contained, for example, both GluR-C Flip and Flop
      splice types.

PMID- 7582118
TI  - Differences in the temporal properties of human longwave- and middlewave
      sensitive cones.
AB  - In recent years a number of electrophysiological and psychophysical observations
      have suggested that the temporal properties of the human longwave- and middlewave
      sensitive cones might be different. However, until now the issue has remained
      unresolved, despite its obvious importance. We have succeeded in probing,
      electrophysiologically, the temporal properties of the two classes, under a range
      of adapting conditions, in a normal human observer. Here we present evidence that
      the temporal properties of these cone types are indeed different and that this
      difference is constant irrespective of the state of light adaptation, suggesting
      that light adaptation has little effect on the kinetics of transduction in human
      cones.

PMID- 7582119
TI  - The neurotrophin receptors TrkA and TrkB are inhibitory for neurite outgrowth.
AB  - To investigate the possibility that the neurotrophin tyrosine kinase receptors
      are also recognition molecules by virtue of their immunoglobulin-like domains,
      the ability of TrkA and TrkB to influence neurite outgrowth was tested in vitro.
      Cell monolayers of fibroblasts transfected to express either the TrkA or TrkB
      receptor reduced neurite outgrowth of phaeochromocytoma PC12 cells by 50-60% when
      compared to mock transfected fibroblasts or fibroblasts transfected with the
      epidermal growth factor receptor. Neurite outgrowth from cerebellar neurons was
      inhibited by 30-40% on these substrates. When a recombinantly expressed fragment
      of TrkA comprising the two immunoglobulin-like domains was coated as a substrate
      in combination with poly-L-lysine and laminin, neurite outgrowth was inhibited in
      a dose-dependent manner. This inhibition of neurite outgrowth was not mediated
      via an interaction with laminin as there is no specific binding of the TrkA
      fragment to laminin. The adhesion of cell bodies to this substrate was not
      affected by the immunoglobulin-like domains. These observations suggest that the
      mammalian neurotrophin receptors not only influence neurite outgrowth by
      neurotrophin triggered activation of the receptor, but also by cell surface
      recognition processes conveyed by the immunoglobulin-like domains.

PMID- 7582120
TI  - Anatomical distribution and postnatal changes in endogenous free D-aspartate and
      D-serine in rat brain and periphery.
AB  - We have investigated the anatomical distribution and postnatal development of D
      aspartate and D-serine in the rat brain and periphery using HPLC techniques. D
      Serine was confined predominantly to the brain throughout postnatal life. At
      birth, a substantial quantity of D-serine was observed throughout the brain
      areas. The cerebral D-serine content increased from birth to postnatal week (PW)
      3 and remained constant thereafter, whereas the cerebellar D-serine content
      peaked at PW1. In contrast, the transient emergence of D-aspartate was found in
      almost all brain and peripheral organs. A substantial quantity of D-aspartate was
      also seen in all brain areas at birth, whereas the D-aspartate content in the
      cerebrum and cerebellum decreased dramatically by PW1 and 7 respectively.
      Further, the D-aspartate content and the ratio of D-aspartate to total aspartate
      were highest in the adrenal at PW3 (608 +/- 70 nmol/g, 45.9%) and in the testis
      at PW14 (221 +/- 7 nmol/g, 57.8%) respectively. Because D-serine potentiates N
      methyl-D-aspartate receptor-mediated transmission through the strychnine
      insensitive glycine site and because D-serine exhibits an N-methyl-D-aspartate
      receptor-related distribution and development, D-serine may be a tenable
      candidate for an intrinsic ligand for the glycine site. In contrast, because the
      periods of maximal emergence of D-aspartate in the brain and periphery occur
      during critical periods of morphological and functional maturation of organs, D
      aspartate could participate in the regulation of these developmental processes of
      organs.

PMID- 7582121
TI  - Electron microscopic observation of substance P-like immunoreactive nerve fibres
      and innervation in the anterior pituitary of macaques.
AB  - The anterior pituitary has recently been confirmed to be innervated by substance
      P-immunoreactive nerve fibres in the monkey and human. The present study
      investigated the morphology of the nerve fibres and their relationship with
      anterior pituitary gland cells in the macaque by means of immunoelectron
      microscopy. Many substance P-immunoreactive and unlabelled nerve fibres were
      distributed among the gland cells or formed nerve fibre bundles. These nerve
      fibres were unmyelinated and varicose, and contained a great many clear and/or
      large dense-cored vesicles. Substance P-immunoreactive cells were seen in the
      pars distalis of the anterior pituitary. Direct contacts between these nerve
      fibres and every cell type of the gland could be ascertained, including substance
      P-immunoreactive cells. Synaptoid contacts were seen among the substance P
      immunoreactive varicosities and somatotropes, opiocortico-melanotropes and
      folliculostellate cells. Typical synapses were identified in somatotropes and
      opiocortico-melanotropes.

PMID- 7582122
TI  - Vulnerability of medium spiny striatal neurons to glutamate: role of Na+/K+
      ATPase.
AB  - In Huntington's disease neuronal degeneration mainly involves medium-sized spiny
      neurons. It has been postulated that both excitotoxic mechanisms and energy
      metabolism failure are implicated in the neuronal degeneration observed in
      Huntington's disease. In central neurons, > 40% of the energy released by
      respiration is used by Na+/K+ ATPase to maintain ionic gradients. Considering
      that impairment of Na+/K+ ATPase activity might alter postsynaptic responsivity
      to excitatory amino acids (EAAs), we investigated the effects of the Na+/K+
      ATPase inhibitors, ouabain and strophanthidin, on the responses to different
      agonists of EAA receptors in identified medium-sized spiny neurons
      electrophysiologically recorded in the current- and voltage-clamp modes. In most
      of the cells both ouabain and strophanthidin (1-3 microM) did not cause
      significant change in the membrane properties of the recorded neurons. Higher
      doses of either ouabain (30 microM) or strophanthidin (30 microM) induced, per
      se, an irreversible inward current coupled to an increase in conductance, leading
      to cell deterioration. Moreover, both ouabain (1-10 microM) and strophanthidin (1
      10 microM) dramatically increased the membrane depolarization and the inward
      current produced by subcritical concentrations of glutamate, AMPA and NMDA. These
      concentrations of Na+/K+ ATPase inhibitors also increased the membrane responses
      induced by repetitive cortical activation. In addition, since it had previously
      been proposed that dopamine mimics the effects of Na+/K+ ATPase inhibitors and
      that dopamine agonists differentially regulate the postsynaptic responses to
      EAAs, we tested the possible modulation of EAA-induced membrane depolarization
      and inward current by dopamine agonists. Neither dopamine nor selective dopamine
      agonists or antagonists affected the postsynaptic responses to EAAs. Our
      experiments show that impairment of the activity of Na+/K+ ATPase may render
      striatal neurons more sensitive to the action of glutamate, lowering the
      threshold for the excitotoxic events. Our data support neither the role of
      dopamine as an ouabain-like agent nor the differential modulatory action of
      dopamine receptors on the EAA-induced responses in the striatum.

PMID- 7582123
TI  - Properties of the ryanodine-sensitive release channels that underlie caffeine
      induced Ca2+ mobilization from intracellular stores in mammalian sympathetic
      neurons.
AB  - The most compelling evidence for a functional role of caffeine-sensitive
      intracellular Ca2+ reservoirs in nerve cells derives from experiments on
      peripheral neurons. However, the properties of their ryanodine receptor calcium
      release channels have not been studied. This work combines single-cell fura-2
      microfluorometry, [3H]ryanodine binding and recording of Ca2+ release channels to
      examine calcium release from these intracellular stores in rat sympathetic
      neurons from the superior cervical ganglion. Intracellular Ca2+ measurements
      showed that these cells possess caffeine-sensitive intracellular Ca2+ stores
      capable of releasing the equivalent of 40% of the calcium that enters through
      voltage-gated calcium channels. The efficiency of caffeine in releasing Ca2+
      showed a complex dependence on [Ca2+]i. Transient elevations of [Ca2+]i by 50-500
      nM were facilitatory, but they became less facilitatory or depressing when
      [Ca2+]i reached higher levels. The caffeine-induced Ca2+ release and its
      dependence on [Ca2+]i was further examined by [3H]ryanodine binding to ganglionic
      microsomal membranes. These membranes showed a high-affinity binding site for
      ryanodine with a dissociation constant (KD = 10 nM) similar to that previously
      reported for brain microsomes. However, the density of [3H]ryanodine binding
      sites (Bmax = 2.06 pmol/mg protein) was at least three-fold larger than the
      highest reported for brain tissue. [3H]Ryanodine binding showed a sigmoidal
      dependence on [Ca2+] in the range 0.1-10 microM that was further increased by
      caffeine. Caffeine-dependent enhancement of [3H]ryanodine binding increased and
      then decreased as [Ca2+] rose, with an optimum at [Ca2+] between 100 and 500 nM
      and a 50% decrease between 1 and 10 microM. At 100 microM [Ca2+], caffeine and
      ATP enhanced [3H]ryanodine binding by 35 and 170% respectively, while binding was
      reduced by > 90% with ruthenium red and MgCl2. High-conductance (240 pS) Ca2+
      release channels present in ganglionic microsomal membranes were incorporated
      into planar phospholipid bilayers. These channels were activated by caffeine and
      by micromolar concentrations of Ca2+ from the cytosolic side, and were blocked by
      Mg2+ and ruthenium red. Ryanodine (2 microM) slowed channel gating and elicited a
      long-lasting subconductance state while 10 mM ryanodine closed the channel with
      infrequent opening to the subconductance level. These results show that the
      properties of the ryanodine receptor/Ca2+ release channels present in mammalian
      peripheral neurons can account for the properties of caffeine-induced Ca2+
      release. Our data also suggest that the release of Ca2+ by caffeine has a bell
      shaped dependence on Ca2+ in the physiological range of cytoplasmic [Ca2+].

PMID- 7582124
TI  - Agonist-induced down-regulation of NMDA receptors in cerebellar granule cells in
      culture.
AB  - In contrast to the acute toxic effect of NMDA on mature cerebellar granule cells,
      chronic treatment with NMDA (140 microM from 1 to 9 days in vitro) did not
      compromise cell survival. Such treatment markedly suppressed NMDA receptor
      activity: at 8 days in vitro NMDA-induced 45Ca2+ influx was reduced by
      approximately 60% and acute exposure to NMDA (highest concentration tested, 1 mM)
      at 9 days in vitro did not cause detectable toxicity. The reduction in NMDA
      receptor activity was accompanied by a significant decrease (approximately 80% at
      9 days in vitro) in the level of the NR1 and the NR2A NMDA receptor subunit
      protein, detected using the selective photoaffinity ligand [125I]CGP55802A. It
      seems, therefore, that the agonist-induced decrease in NMDA receptor activity is
      due to receptor down-regulation. In contrast to the marked influence of chronic
      NMDA exposure on the cellular content of the NMDA receptor subunit proteins, mRNA
      levels of the different subunits (NR1, NR2A, NR2B and NR2C) were not
      significantly affected. It seems, therefore, that agonist-induced down-regulation
      of the NMDA receptor involves critically mRNA translation and/or post
      translational regulation.

PMID- 7582125
TI  - Alpha 1-adrenergic effects on dopamine neurons recorded intracellularly in the
      rat midbrain slice.
AB  - Previous studies have indicated excitatory adrenergic effects on midbrain
      dopamine systems. To investigate the cellular mechanisms, intracellular
      recordings were made from neurons in perfused, oxygenated slices of male rat
      midbrain. Electrophysiological and pharmacological parameters were used to
      identify cells as principal (presumably dopaminergic) neurons as opposed to
      secondary (presumably GABAergic) neurons in the substantia nigra zona compacta
      and the ventral tegmental area. Noradrenalin (10-100 microM) hyperpolarized 57%
      of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine
      D2 receptor antagonist, completely blocked noradrenalin-induced
      hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58%
      of all principal neurons and had no effect in 42%; this effect was mimicked by
      the alpha-adrenergic agonist phenylephrine (10-30 microM) which depolarized 43 of
      72 cells. The alpha 1 receptor antagonist prazosin (30-100 nM) completely blocked
      the membrane depolarization produced by either noradrenalin or phenylephrine in
      all cells tested, whereas alpha 2- and beta-adrenergic agents had no effect. In
      voltage clamp, phenylephrine evoked an inward current (at -60 mV) and reduced
      cord conductance by 0.81 +/- 0.14 nS (n = 4). Inward current evoked by
      phenylephrine became outward at -96 +/- 8 mV, which is near the membrane reversal
      potential for potassium as predicted by the Nernst equation. Phenylephrine also
      depolarized secondary cells and increased the frequency of spontaneous GABAA
      receptor-mediated postsynaptic potentials recorded in both principal and
      secondary cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582126
TI  - Morphological fate of rhombomeres in quail/chick chimeras: a segmental analysis
      of hindbrain nuclei.
AB  - Quail rhombomeres two to six (r2-r6) were individually grafted homotopically into
      the hindbrain of chick embryos at 2 days of incubation. Nine to 10 days after the
      operation the chimeric embryos were fixed and processed for parallel
      cytoarchitectural and immunocytochemical study (with an anti-quail antibody) in
      order to map the anatomical fate of the grafted tissue. Emphasis was placed on
      conventionally identified and distinct neuronal populations composing the sensory
      and motor longitudinal columns. Grafted rhombomeres consistently developed as
      complete transverse slices of the chimeric hindbrain. Interrhombomeric cell
      migration was either sparse or restricted to specific nuclei. The cranial nerve
      motor nuclei showed rhombomeric origins consistent with the patterns described in
      early embryos. Unexpectedly, alar r2 was found to form the auricular part of the
      cerebellum. As regards the cochlear nuclei, we found that nucleus angularis
      derives from r3 to r6, nucleus laminaris from r5 to r6, nucleus magnocellularis
      from r6 to r7 and nucleus olivaris superior from r5. The nuclei of the lateral
      lemniscus originated between r1 and r3. We also delimited the respective
      rhombomeric subdivisions of the sensory vestibular and trigeminal columns, both
      of which extend from r1 caudalwards throughout the hindbrain. There were
      consistently some interrhombomeric neuronal migrations inside the vestibular
      column, some motor nuclei and the reticular formation, involving only one
      rhombomere length. The pontine nuclei, which extended from r1 to r7, showed
      neuronal migrations that crossed several rhombomeres. On the whole, these results
      represent the first anatomical analysis of the mature avian hindbrain in terms of
      rhombomere-derived domains.

PMID- 7582127
TI  - Fibroblast growth factors regulate calcitonin gene-related peptide mRNA
      expression in rat motoneurons after lesion and in culture.
AB  - In this study, we have investigated the effect of fibroblast growth factors (bFGF
      and FGF-5) and brain derived neurotrophic factor (BDNF) on the expression of
      calcitonin gene-related peptide (CGRP) in rat motoneurons in vivo and in vitro.
      Following sciatic nerve transection in adult rats, the levels of alpha-CGRP and
      beta-CGRP mRNA were up- and down-regulated respectively in axotomized
      motoneurons, revealed by in situ hybridization histochemistry. Local
      administration of 1 microgram bFGF was able to entirely abolish the up-regulation
      of alpha-CGRP mRNA, and to further down-regulate beta-CGRP. These effects, albeit
      less pronounced, were still evident with 0.2 micrograms bFGF. In contrast, bFGF
      did not attenuate the lesion-induced decrease of choline acetyltransferase (ChAT)
      mRNA. Administration of BDNF did not significantly alter the expression of CGRP
      or ChAT mRNA in axotomized motoneurons. Both alpha- and beta-CGRP mRNAs could be
      detected by PCR in enriched motoneuron cultures prepared from rat embryos at
      embryonic day 14-15. Comparing the amplification of alpha- and beta-CGRP mRNAs
      with that of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in
      parallel samples, we found that cultures treated with FGF-5 had a lower ratio of
      alpha- and beta-CGRP mRNA to GAPDH mRNA, than did control or BDNF-treated
      cultures. BDNF, on the other hand increased alpha-CGRP and decreased beta-CGRP
      mRNA levels, though these effects were moderate compared with the effects of FGF
      5. The results obtained in this study suggest that members of the FGF family of
      growth factors influence the expression of CGRP in rat motoneurons, and that the
      increase of this neuropeptide induced by axotomy may, at least in part, be due to
      deprivation of these target-derived factors.

PMID- 7582128
TI  - All-or-none excitatory postsynaptic potentials in the rat visual cortex.
AB  - Intracellular recordings were obtained from supragranular neurons in slices of
      the rat visual cortex. In approximately 25% of the cells large (0.5-1.6 mV)
      excitatory postsynaptic potentials (EPSPs) of constant amplitude were observed
      after minimal, presumably single-fibre stimulation. The amplitude variance of
      these large EPSPs was surprisingly small and within the range of the variance of
      the noise. These EPSPs could be reduced in amplitude by paired-pulse and low
      frequency stimulation or by raising extracellular Mg2+ concentration. Reduced
      EPSPs could either continue to behave as all-or-none responses, or they could
      fluctuate between several amplitude levels. Conversely, responses where the
      amplitude fluctuated from trial to trial under control conditions could be
      converted into large all-or-none responses by paired-pulse facilitation. This
      indicates that the large all-or-none EPSPs were composed of several subunits,
      probably reflecting the action of several different release sites. It is
      concluded that these release sites are either independent and operate with a
      probability close to 1 or, if operating with a lower probability, are coordinated
      by a mechanism which synchronizes release. Several observations suggest that
      release probabilities can switch from values close to 1 to 0 with repetitive
      stimulation or high Mg2+ concentration. Thus, a substantial fraction of single
      fibre inputs to supragranular cells possess synapses which operate with high
      synaptic efficiency and extremely low variance under control conditions but can
      undergo drastic changes in efficacy when release probabilities are interfered
      with. Such modifications of release probability could serve as an effective
      mechanism to regulate the gain of synaptic transmission.

PMID- 7582129
TI  - TGF-beta s and cAMP regulate GAP-43 expression in Schwann cells and reveal the
      association of this protein with the trans-Golgi network.
AB  - We have shown previously that growth-associated protein 43 (GAP-43) is expressed
      by rat Schwann cells and is restricted to non-myelin-forming Schwann cells in
      vivo. Here we examined the regulation of GAP-43 using agents that are known to
      control Schwann cell differentiation in vitro. GAP-43 protein and mRNA levels are
      decreased by forskolin and other agents that elevate intracellular cAMP (and
      promote expression of the myelinating Schwann cell phenotype). We also found that
      expression of GAP-43 protein but not mRNA is down-regulated by transforming
      growth factor betas (TGF-beta s). Moreover, TGF-beta treatment of Schwann cells
      results in cell clumping, process retraction and disappearance of GAP-43 from the
      plasma membrane, revealing that GAP-43 is associated with the Golgi apparatus.
      This association was confirmed by partial overlap of GAP-43 with the trans-Golgi
      network marker (23c) and the disruption of the Golgi with brefeldin A or monensin
      leading to altered GAP-43 distribution. Golgi-associated GAP-43 appeared to have
      the same molecular weight as the plasma membrane-associated GAP-43. Thus these
      results show that GAP-43 expression in Schwann cells is subject to regulation by
      both extracellular and intracellular signalling molecules and that Schwann cell
      GAP-43 is often associated with the Golgi apparatus.

PMID- 7582130
TI  - Development of electrical membrane properties and discharge characteristics of
      superior olivary complex neurons in fetal and postnatal rats.
AB  - Although hearing onset occurs relatively late during ontogeny of rats [around
      postnatal day (P) 12], anatomical brainstem connections are formed much earlier
      and are present before birth, indicating that a substantial amount of maturation
      occurs without acoustic input. Electrical activity is thought to influence
      neuronal development, but the physiological properties of auditory brainstem
      neurons during perinatal maturation are barely known. The present study focuses
      on the development of electrophysiological membrane properties of neurons in the
      rat's superior olivary complex (SOC), the first binaural station in the mammalian
      auditory brainstem. In in vitro slice preparations, intracellular recordings were
      obtained from 115 SOC cells from embryonic day (E) 18 to P17, and cells were
      morphologically identified by intracellular injection of biocytin or neurobiotin.
      By E18, i.e. 4 days before birth, SOC neurons were capable of generating Na(+)
      dependent action potentials. Several passive and active membrane properties,
      including the resting potential, spike threshold and spike amplitude, did not
      change with development. In contrast, input resistance, time constant and spike
      duration decreased significantly, and maximal spike frequency increased
      significantly during the age period sampled. Our results show that rat SOC
      neurons display mature as well as immature electrical membrane properties during
      the same developmental period when anatomical connections are refined and when
      the soma-dendritic morphology develops. We conclude, therefore, that their
      membrane properties represent adequate physiological adaptations to the immature
      auditory brainstem microcircuits and that they form a basis upon which the
      development of these microcircuits is shaped.

PMID- 7582132
TI  - Developmental regulation of acetylcholinesterase transcripts in the mouse
      diaphragm: alternative splicing and focalization.
AB  - We studied the splicing and compartmentalization of acetylcholinesterase (AchE)
      mRNAs during muscle differentiation in the mouse, both in vitro and in vivo. We
      used the polymerase chain reaction (PCR) to analyse AChE mRNAs in cultures of the
      myogenic C2 and Sol8 cell lines, and in the developing diaphragm, from embryonic
      day 14 (E14). We characterized three types of alternatively spliced AChE mRNAs,
      encoding catalytic subunits that differ by their C-terminal regions (R, H and T).
      The T transcript is predominant in all cases and represents the only AChE mRNA in
      the adult muscle. We detected the presence of the minor R and H transcripts in
      the myogenic cell lines, both as myoblasts and differentiated myotubes, and also
      in the diaphragm from E14 until birth. At E14 the R transcript represents
      approximately 1% of AChE mRNA and the level of the H transcript is still lower.
      By in situ hybridization, we found that the T AChE mRNAs begin to preferentially
      accumulate at the level of the first neuromuscular contacts in the mouse
      diaphragm and other muscles as early as E14, e.g. concomitantly with mRNAs
      encoding the receptor subunits. This suggests that a common control mechanism
      ensures the synaptic focalization of mRNAs encoding the cholinergic proteins AChE
      and acetylcholine receptor during muscle development.

PMID- 7582133
TI  - Focal adhesion kinase in rat central nervous system.
AB  - Focal adhesion kinase (pp125FAK, FAK) is a 125 kDa non-receptor tyrosine kinase
      enriched in focal adhesions of various cell types, where it is thought to
      transduce signals triggered by contact with the extracellular matrix. We have
      studied the expression and localization of FAK in rat CNS. Immunoblotting,
      immunohistochemistry and in situ hybridization revealed the presence of FAK in
      all regions of the adult brain and demonstrated its enrichment in specific
      neuronal populations of the cerebral and cerebellar cortex, as well as in the
      hippocampus. During development, FAK protein levels were highest around birth in
      cerebral cortex and caudate putamen and decreased in the adult. In situ
      hybridization revealed enrichment of FAK mRNA in the ventricular germinative and
      external layers during the last period of embryonic growth. In primary cultures
      FAK immunoreactivity was localized in focal adhesions in astrocytes, whereas in
      developing neurons the highest levels were found in growth cones and perikarya.
      In the growth cone, FAK immunoreactivity colocalized with actin filaments. In
      mature neurons FAK appeared to be distributed in the whole cytoplasm, with no
      enrichment in any cellular compartment. Our results demonstrate the presence of
      high levels of FAK in rat CNS, maximal during development but persistent in the
      adult. Its enrichment in growth cones suggests that it may play a role in neurite
      outgrowth, as well as in plasticity in the adult.

PMID- 7582131
TI  - Stimulation of Ca(2+)-activated non-specific cationic channels by phospholipase C
      linked glutamate receptors in synaptoneurosomes?
AB  - The regulation of intracellular Ca2+ concentration ([Ca2+]i) by glutamate
      metabotropic receptors (mGluR) was studied in 8-day-old rat forebrain
      synaptoneurosomes using spectrofluorimetric methods. Here we demonstrate that
      metabotropic glutamate agonists induce in rat brain synaptoneurosomes a Ca2+
      influx largely dependent upon the presence of Ca2+ in the external medium. The
      pharmacological profile of this influx is strongly correlated with the
      pharmacological profile of the activation of phosphoinositide hydrolysis, i.e.
      quisqualic acid >> 1S,3R-amino-1-dicarboxylate-1,3 cyclopentane approximately
      equal to glutamate. This metabotropic glutamate receptor-induced Ca2+ influx is
      insensitive to voltage-dependent Ca2+ channel antagonists and occurs through a
      Mn2+ impermeant pathway. The study of the rapid kinetics shows that this influx
      is triggered after a 300 ms delay compared with that elicited by depolarizing
      agents and Ca2+ ionophore A23187. In order to assess further if mGluR stimulate
      this influx through the recruitment of inositol triphosphate (IP3)-sensitive
      intracellular Ca2+ stores, we have tested the effect of thapsigargin on membrane
      potential and intracellular Ca2+ simultaneously. Thapsigargin induces a
      depolarization of the synaptoneurosomal membrane followed by a massive Ca2+
      influx, occurring via a Mn2+ nonpermeant route. This depolarizing effect is
      sensitive to the presence of the intracellular Ca2+ chelator [1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetoxymethyl ester], and partially sensitive
      to extracellular Na+, but insensitive to the presence of extracellular Ca2+.
      Taken together, our data suggest that mGluR stimulate self-maintained increases
      of [Ca2+]i in rat forebrain synaptoneurosomes via the activation of a multistep
      mechanism, sequenced in the following steps: (i) mGluR-induced IP3 synthesis;
      (ii) IP3-stimulated intracellular Ca2+ release; (iii) Ca(2+)-activated non
      specific cation channel, leading to local depolarization and a Ca2+ influx; and
      (iv) activation of Ca(2+)-sensitive phospholipase C.

PMID- 7582134
TI  - NADPH diaphorase-containing nonpyramidal cells in the rat hippocampus exhibit
      differential sensitivity to kainic acid.
AB  - Neurons containing nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase
      exhibit high resistance to several excitotoxins. In the neocortex and striatum,
      however, these neurons are sensitive to kainic acid. Here we report that, 2 weeks
      after i.p. injection of kainic acid, the number of NADPH diaphorase neurons in
      the hilus and CA1 subfield was decreased, whereas the cell counts in the other
      hippocampal areas were to a great extent similar to those for the controls. We
      propose that the loss of NADPH diaphorase neurons in the hippocampus after
      systemic injection of kainic acid is associated with the pathophysiological
      processes involved in the spreading of epileptic seizure activity rather than to
      the direct neurotoxic effect of the kainic acid per se.

PMID- 7582135
TI  - G-protein modulation of glycine-resistant NMDA receptor desensitization in rat
      cultured hippocampal neurons.
AB  - Activation of N-methyl-D-aspartate (NMDA) subtype glutamate receptors increases
      the excitability of most neurons within the CNS. A common feature of ionotropic
      glutamate receptors is their ability to undergo desensitization. In the present
      experiments we have examined the role of guanine nucleotide-binding proteins (G
      proteins) in the regulation of NMDA receptor desensitization. Repeated NMDA
      receptor activation with 2 mM extracellular Ca2+ increased the degree of glycine
      resistant NMDA receptor desensitization of subsequent responses to NMDA recorded
      in the presence of 0.2 mM Ca2+. The recovery of glycine-resistant NMDA receptor
      desensitization after repeated NMDA receptor activation in the presence of 2 mM
      Ca2+ was significantly reduced in neurons intracellularly dialysed with guanosine
      5'-O-(3-thiotriphosphate), guanosine-5'-triphosphate or AlCl3 and CsF, compounds
      known to activate G-proteins. Intracellular dialysis with guanosine-5'-O-(2
      thiodiphosphate), adenosine triphosphate, adenosine triphosphate, or adenosine-5'
      O-(3-thiotriphosphate) was ineffective. The calcium permeability of NMDA receptor
      channels was not altered by intracellular dialysis with GTP gamma S. This
      suggests that modulation of NMDA receptor desensitization by G-proteins
      represents a novel mechanism for regulation of glutamate-gated ion channel
      activity.

PMID- 7582136
TI  - Born of necessity: the dynamic synergism between advancement of analytic methods
      and generation of new knowledge.
AB  - Serious studies of the results of clinical interventions, such as those of heart
      valve surgery, employ mathematical and statistical methods and modes of
      expression and presentation that are complex. I, along with my colleagues, am
      guilty of developing some of these methods. However, in this address I trace the
      more than three centuries of development that has led to present methodology,
      demonstrating that each increase in complexity was born of the necessity to
      reflect clinical reality. These methods include survival analysis, and
      particularly its central theme, the hazard function, from its invention by a
      storekeeper during the Plague to the multiple phase hazard method developed by
      us. Importantly, contemporary methods permit patient-specific predictions that
      are useful for recommending therapy and for informed patient consent. In
      contemporary medicine, molecular-level research would seem to hold the promise of
      making observational clinical studies obsolete; yet a flurry of so-called
      Outcomes Research has emerged. However, the danger now is that new forces and
      philosophies are driving that interest that are not as strongly tuned to the
      necessities of improving individual patient care and longitudinal outcome as has
      been the case in the past.

PMID- 7582137
TI  - Measuring the quality of life.

PMID- 7582140
TI  - An appraisal of the Ross procedure.

PMID- 7582139
TI  - Follow up of patients after valvular surgery: mail vs. telephone.
AB  - A study was undertaken to compare the results of patient follow up done by mail
      and by telephone. Using valve follow up questionnaires recently received by mail,
      100 patients were randomly selected from this group for further follow up by
      telephone. Interviews were conducted while blinded to the mail response. Patients
      were questioned as to their functional status (NYHA), improvement as a result of
      surgery (IMP), incidence of reoperation (REOP) or bacterial endocarditis (SBE)
      and thromboembolic complications (TE). They were also asked whether they would
      prefer future follow up by mail or telephone. Analysis using the kappa
      coefficient and McNemar's test revealed a difference (p < 0.001) in NYHA when
      comparing mail and telephone responses but no difference in either IMP or TE.
      There was no incidence of REOP or SBE. Sixty-six percent of patients had no
      preference in type of future follow up and of the remaining 33%, two-thirds
      preferred to be contacted by phone. It appears that NYHA is significantly
      overestimated by the patient whereas the two methods of follow up are comparable
      when assessing IMP and TE. It should be noted, however, that patients seem to
      have difficulty in identifying the occurrence of TE and in differentiating
      between stroke and TIA.

PMID- 7582138
TI  - Similar quality of life after heart valve replacement with mechanical or
      bioprosthetic valves.
AB  - The goal of this study was to determine if there was a difference in the quality
      of life (QoL) between patients receiving bioprosthetic (Biocor, BIO) or
      mechanical (St. Jude Medical, SJM) valve prosthesis. In January 1993 we assessed
      the psychological outcome of heart valve surgery among 183 (87 BIO, 96 SJM) of
      220 survivors in a selected and matched cohort of 140 BIO and 140 SJM recipients
      who had their valve replacement between 1983 and 1989. The BIO and SJM groups
      were equal in terms of mean age, gender, valve position, educational level,
      marital status and follow up time. Questions concerning QoL, in terms of coping
      capacity, social support, and general emotional status as well as emotions
      concerning valve-related complications, were answered by the patients marking a
      non-graded visual analogous scale, ranging from total agreement to total
      disagreement. We found no significant difference between patients receiving BIO
      and those receiving SJM prostheses regarding coping capacity (62 +/- 2 vs. 65 +/-
      2), social support (77 +/- 3 vs. 76 +/- 2), or emotional status (63 +/- 3 vs. 65
      +/- 3). When subdividing patients by age below and above 60 years, gender,
      functional class, valve position and complication, we found several significant
      differences, but the two prosthetic groups were largely similar. Females had a
      significantly lower level of coping capacity and emotional status than males.
      Coping capacity and emotional status were significantly correlated with
      functional class, while social support was not. Coping capacity tended to be
      lower among patients who had experienced complications and this was more
      pronounced with BIO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582142
TI  - Repair of complex left ventricular outflow tract obstruction with a pulmonary
      autograft.
AB  - The surgical relief of complex multilevel left ventricular outflow tract (LVOT)
      obstruction remains a challenging surgical problem. We present a new operation
      which combines the concepts of aortoventriculoplasty, extended aortic root
      replacement and the use of a pulmonary autograft. Sixteen patients underwent this
      operation: 11 patients after previous attempts to relieve diffuse subvalvular
      stenosis and five patients who presented excessive gradients over an outgrown
      aortic valve prosthesis. All patients, except one survived the operation. One
      patient developed massive right ventricular infarction and was transplanted after
      five days. Another patient developed complete heart block and transient tricuspid
      regurgitation after a septal infarction. One patient remained in congestive heart
      failure and died suddenly after 17 months. All other patients are in NYHA class I
      after a mean follow up of 21 +/- 12 months. One patient developed progressive
      dilatation of the neo-aortic root and was reoperated four years after initial
      surgery. All other patients showed laminar flow in the LVOT and excellent
      function of the autograft and homograft valve at follow up. This operation might
      present a durable or even a definitive solution in the management of these
      complex left ventricular outflow tract obstructions.

PMID- 7582141
TI  - Expanding indications for the Ross operation.
AB  - During the past 2.5 years, 50 Ross operations have been performed at
      Rigshospitalet in Copenhagen in a broad range of patients with aortic valve
      disease including children and adults from 6 weeks to 71 years of age. Many
      patients had complicating conditions including endocarditis (n = 13, eight
      native, five prosthetic valve), prosthetic valve dysfunction (n = 4), subvalvular
      obstruction (n = 3) treated by septal myectomy (n = 1) or modified Konno
      operation (n = 2), ascending aortic aneurysm (n = 2), ventricular septum defect
      (n = 1), mitral valve disease (n = 6), rheumatic heart disease (n = 4), coronary
      artery disease (n = 1), and extreme obesity (n = 1). All operations were
      performed as free-standing total aortic root replacements. The results have been
      encouraging with low mortality (2%) and no major morbidity. One patient has been
      reoperated because of autograft insufficiency due to left coronary cusp prolapse
      and two additional patients have grade 2 autograft insufficiency and are being
      followed closely. Two patients have developed early pulmonary homograft stenosis,
      which has required pulmonary homograft replacement. Despite these problems, we
      are enthusiastic about this operation and believe it may emerge as operation of
      choice for most patients under 60-65 years of age with aortic valve disease and
      for patients with prosthetic or advanced native aortic valve endocarditis. With
      increasing frequency, our choice has been to proceed with a Ross operation, and
      currently, our only absolute contraindication is Marfan's syndrome. Based on
      reported recurrent disease in patients with rheumatic valve disease, the
      autograft should be used with caution for this indication.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7582143
TI  - Total aortic root replacement with pulmonary autografts: short term results in 45
      consecutive patients.
AB  - From March 1992 through March 1995 we have performed 45 Ross procedures for total
      aortic root replacement in our institution. There were 32 males and 13 females
      with a mean age of 31 years (range: 3-49 years). Indications for surgery were:
      aortic stenosis (n = 20), aortic regurgitation (n = 16), native valve
      endocarditis (n = 6), replacement of prosthetic valve (n = 3). Of these 45
      patients 13 (28%) had at least one prior repair. Additional procedures were
      Dacron graft extension of the autograft (n = 7), enlargement of aortic annulus (n
      = 3), mitral valve repair (n = 2), CABG (n = 1), closure of VSD (n = 1). The mean
      cross-clamp time was 132 minutes (76-187 minutes) and the mean bypass time 156
      minutes (106-240 minutes). There were two postoperative cardiac deaths, not valve
      related, and five non-lethal postoperative complications: right ventricular
      failure (n = 1), low cardiac output (n = 1), sternal re-entry for bleeding (n =
      3). The follow up is complete (1.5-37 months) for the 43 survivors. There was one
      non-cardiac late death (acute fulminating hepatitis) in an eight years old boy
      eight months post-operatively. Discharge echo-Doppler studies showed normal
      autograft and homograft valve function except in one patient who had a grade two
      aortic regurgitation. Serial echo-Doppler studies showed no significant
      progression of aortic regurgitation, no significant pulmonary gradients, no
      dilatation of the autografts during the follow up. It is suggested in conclusion
      that aortic root replacement with a pulmonary autograft is a safe procedure in
      selected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582144
TI  - Insertion of the pulmonary autograft as an inclusion cylinder--modifications to
      existing techniques.
AB  - Ten pulmonary autograft procedures have been performed (mean age 27, range 19-40
      years) all using root replacement techniques. In six operations the inclusion
      cylinder method was performed, as first preference. Because of root asymmetry
      associated with the congenitally deformed aortic valves, modifications to the
      standard procedure were necessary in four out of the six patients. In one, the
      aortic annular dimension was reduced by a Dacron collar inserted around the
      proximal autograft suture line. In another the sinotubular dimension was trimmed
      by wedge excision of part of the non-coronary sinus and ascending aortic
      tailoring. In the remaining two patients, pericardial patch enlargement of the
      lower ascending aorta was employed to increase the sino-tubular diameter. In the
      remaining four patients, full free-standing root replacement was performed as
      second best option because of inexperience (early in the series), or coronary
      artery anomalies, and more severe degrees of root symmetry (later in the series).
      All 10 patients are alive and have been recently reviewed with Doppler
      echocardiography (mean follow up 14 months, range 4-29 months). Mean aortic
      gradient was 5 mmHg, aortic regurgitation minimal (trivial seven, mild three),
      good pulmonary homograft function and normalization of left ventricular function
      were documented. In summary, we aim to perform the inclusion cylinder technique
      in most cases, and it is presumed that this may result in better long term aortic
      valve competence.

PMID- 7582145
TI  - Experimental basis for autograft growth and viability.
AB  - An experimental model has been designed to evaluate the potential of growth of
      aortic vascular autografts and homografts. In 25 young rabbits a graft
      interposition was performed at the level of the infrarenal aorta, with micro
      surgical techniques. Different groups included fresh autografts, fresh and
      cryopreserved homografts and controls. Animals were allowed to grow normally and
      were sacrificed when adult, at the mean weight of 2.99 kg. We studied for each
      case the growth of the native aorta and that of the graft, and calculated the
      growth-ratio (growth of the graft/growth of native vessel). Grafts and adjacent
      aorta were histologically studied. The growth in terms of increase in diameter of
      the native aorta was identical between the four groups (from 1.97 +/- 0.14 mm to
      2.86 +/- 0.23 mm). Growth of the graft was normal (mean growth ratio 1.08 +/-
      0.21) for autografts. Growth was absent (mean ratio 0.12 +/- 0.15) for fresh and
      cryopreserved homografts (p = 0.001). Histologic study showed normal optical
      microscopic aspects (endothelial layer, intima and media thickness and
      cellularity) when growth had been normal and, when growth had been absent,
      aspects compatible with rejection including mainly intima hyperplasia and media
      attenuation. In conclusion, normal growth of the arterial autografts was
      confirmed, the histologic features of these grafts were normal, but homologous
      aortic grafts, fresh or cryopreserved, never showed any growth potential.

PMID- 7582146
TI  - Ten year experience with pulmonary allografts in children.
AB  - Infants who have undergone pulmonary valve allograft reconstruction of the right
      ventricular outflow tract experience an increased incidence of allograft
      fibrocalcification and valvar insufficiency compared to older allograft
      recipients. Since April 1985, 186 cryopreserved pulmonary valve allografts have
      been used for right ventricular outflow tract reconstruction in pediatric
      patients at The Children's Hospital and the University of Colorado Health
      Sciences Center in Denver. One hundred and forty-six patients were one to 18.4
      years of age (mean age: 5.0 years) and 40 children were younger than one year of
      age at operation (mean age: 4.4 months). In the older patient group, there were
      15 hospital deaths (10%) and one child with dilated cardiomyopathy and cardiac
      failure underwent cardiac transplantation two days postoperatively. One hundred
      and thirty operative survivors have been followed clinically for a mean of 4.6
      years. One child was lost to follow up and one patient with myocardial
      dysfunction required cardiac transplant 3.8 years postoperatively. There have
      been five late deaths (4%), one of which resulted from accidental trauma. Five
      children (4%) have undergone reoperation to replace their valve allograft at 1.3
      to 9.8 years after the initial allograft procedure. In the infant group, there
      were nine hospital deaths (23%). During follow up averaging 3.0 years, there have
      been nine late deaths (29%) and five children (16%) have undergone valve
      allograft explant 2.0 months to 3.5 years following implantation. Allografts are
      technically desirable in small children for whom surgical repair alternatives are
      limited.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582148
TI  - Aortic and pulmonary homografts for right ventricular outflow tract
      reconstruction.

PMID- 7582149
TI  - Preliminary experience with pulmonary autografts.
AB  - Between July 1994 and March 1995, seven patients (six male) with a mean age of 27
      years (range 18 to 34 years) were selected for aortic valve replacement with a
      pulmonary autograft (Ross operation). The aortic valve disease was isolated
      insufficiency in four cases, stenosis in one and mixed lesion in two. Three
      patients had a bicuspid aortic valve. Previous cardiac surgical procedures had
      been performed in two cases (coarctation repair and valvuloplasty in one;
      isolated aortic valvuloplasty in one). Two patients were in NYHA class II and
      five in class III. In two cases the autograft was inserted as a scalloped
      subcoronary implant. Four patients had total aortic root replacement with re
      implantation of the coronary ostia. The RVOT was reconstructed with a
      cryopreserved homograft (five pulmonary two aortic). The aortic cross-clamp time
      was 150 +/- 10 minutes with a total bypass time of 212 +/- 14 minutes. There was
      neither operative nor late mortality. Postoperative echocardiography revealed
      trivial autograft insufficiency in one case with a mean transvalvular gradient of
      15.8 mmHg. All patients improved symptomatically (100% in NYHA class I). Freedom
      from reoperation, valve related complications and endocarditis is 100% at a mean
      follow up of 5.6 months (range 1-9 months). This preliminary experience supports
      the concept of pulmonary autograft implantation in selected patients.

PMID- 7582150
TI  - Three years surgical and clinical experience with the Ross procedure in adults.
AB  - From January 1991 to October 1994, 20 Ross procedures were performed. Mean age
      was 39.70 +/- 7.72 years, range 26 to 56 years. Male/female ratio was 14/6.
      Nineteen operations were elective, one was semiurgent. Predominant valvular
      lesion was stenosis in seven patients, aortic regurgitation in four, mixed
      disease in eight and prosthetic dysfunction in one patient. Twelve pulmonary
      autografts were implanted in the subcoronary (SC) position, eight as an
      intraaortic cylinder (inclusion technique (INCL)). Early mortality (< 30 days
      postoperative) was one (5.0%), there was no late mortality. Reoperation for valve
      failure occurred in two patients (10.0%). Additional CABG was performed in two
      patients (10.0%) for technical reasons. Major ECG changes were detected in five
      patients (three RBBB, two ischemia). No thromboembolic events were reported. Mean
      follow up was 21.2 months. Aortic insufficiency (AI) at one year was similar in
      the SC and INCL group. AI grade I in SC: 60%, in INCL: 60%; AI grade II in SC
      10%, in INCL: 20%. At two years AI grade I occurred in 100% of the SC group. At
      three years AI grade I occurred in 75% of the SC group and AI grade II in 25%. No
      patients of the INCL group had two- or three-year follow up. At discharge slight
      pulmonary regurgitation was traced in only three patients and it remained stable
      during the follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582151
TI  - A technique to prevent bleeding after Ross procedure.
AB  - From October 1993 through August 1994, 21 patients underwent Ross procedures. In
      the first 12 patients bleeding and/or sequelae resulted in three deaths. In the
      subsequent nine patients, we modified the technique to prevent bleeding from the
      raw area of the right ventricular outflow tract (RVOT) without further mortality.
      This is described in detail.

PMID- 7582147
TI  - Performance of aortic and pulmonary homografts in the right ventricular outflow
      tract in children.
AB  - Cryopreserved homografts have been used at the German Heart Institute Berlin
      since October 1986. Until 31st May 1994, cryopreserved aortic (AA) or pulmonary
      (PA) homografts were implanted in the pulmonary position and followed up in 104
      patients. The mean age at operation was 5.5 years. The patients were treated with
      3-5 mg/kg aspirin daily after the operation for three months. They all had
      routine echocardiographic evaluation of their homografts, 47 patients were
      studied by heart catheterization. Excellent functional results of the homograft
      valves were found in 92 patients (88.5%). Early degeneration of the homograft
      conduit leading to reoperation was observed in 12 patients. Freedom from wall
      calcification was 18% in aortic and 78% in pulmonary homografts while freedom
      from valve dysfunction in aortic and pulmonary homografts at 60 months was 60%
      and 67%, respectively. Freedom from reoperation was 81% overall, 78% and 84% in
      patients with aortic and pulmonary homografts respectively (p < 0.05). In
      conclusion, pulmonary homograft has proved to be more durable than the aortic
      homograft in the pulmonary position, hence it is the preferential valve for RVOT
      reconstruction in children.

PMID- 7582152
TI  - The Mitroflow pericardial valve: clinical performance to 10 years.
AB  - From 1983 to 1992, 366 patients received 407 Mitroflow pericardial bioprostheses
      at our institution. Mean age was 62 +/- 14 years (range: 15-86 years). There were
      229 isolated aortic valve replacements (AVR), 96 isolated mitral valve
      replacements (MVR), 39 double mitral and aortic valve replacements (DVR) and four
      tricuspid replacements. Mean follow up was 6 +/- 2.33 years ranging from 1.67 to
      10.9 years. Total follow up was 1791 patient-years. Overall survival was 77.2 +/-
      2.2% at five and 56.2 +/- 6.4% at 10 years. It was 74 +/- 3% and 56.2 +/- 5.3%
      after AVR, 78.3 +/- 4.4% and 55.7 +/- 8.8% after MVR, 81 +/- 6.4% and 36.6 +/-
      16.5% after DVR at five and 10 years, respectively. Freedom from structural valve
      deterioration (SVD) was 95 +/- 1.2% and 36.7 +/- 8.1% at five and 10 years for
      all valves, 96.9 +/- 1.3% and 39.2 +/- 9.8% for AVR, 91.7 +/- 3.2% and 36.4 +/-
      10% for MVR. There was no difference in freedom from SVD between AVR and MVR. The
      freedom from SVD in patients older than 70 years of age was 100% and 93.9 +/-
      5.8% at five and 10 years, respectively. Freedom from reoperation was 94.7 +/-
      1.37% and 28.36 +/- 7.5% at five and 10 years for all valves, 96.2 +/- 1.5% and
      38.6 +/- 9.7% for AVR, 91.7 +/- 3.2% and 36.4 +/- 10% for MVR. The denaturation
      process did not lead to acute hemodynamic deterioration. Pathologic findings were
      cuspal tears (one or more) associated with structural tissue changes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582154
TI  - High intensity transcranial Doppler signals (HITS) after prosthetic valve
      implantation.

PMID- 7582153
TI  - Transcranial Doppler ultrasound signals associated with prosthetic heart valves:
      an in vitro study.
AB  - The application of transcranial Doppler (TCD) ultrasonography to asymptomatic
      prosthetic heart valve patients can result in detection of localized bursts of
      high intensity signals, similar to those caused by the passage of emboli. The
      origin of these signals is not known. In order to investigate this phenomenon in
      a simplified, more controllable environment, a TCD machine was used to record
      flow downstream from mechanical prosthetic heart valves in a mock circulatory
      loop. The model, which uses a saline solution seeded with silk particles (< 15
      micrometers) as the circulatory fluid, recreates the principal hydrodynamic
      characteristics of the left heart and systemic circulation. Reproducibility of
      the system was established through repeated testing of a Monostrut valve. Three
      different mechanical valve types, (Monostrut, Medtronic Hall, St. Jude Medical)
      were tested over a range of simulated cardiac outputs, and the effect of valve
      size was investigated with four Omniscience tilting disc valves (21, 23, 25 and
      29 mm). Average energy of the reflected Doppler signal was used to quantify the
      amount of high intensity Doppler signal, QTCD. TCD signals recorded in vitro were
      visually and aurally similar to those found in prosthetic heart valve patients.
      All valve types generated exponentially more QTCD with increasing simulated
      cardiac output. Differences amongst valve types were only significant at higher
      flow outputs, with the Monostrut valve producing the greatest QTCD. Larger valves
      consistently generated greater QTCD than smaller valves. In conclusion, TCD
      signals found in prosthetic heart valve patients can be reproduced, at least
      qualitatively, using a mock circulatory loop which does not incorporate the
      formed elements of blood.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582155
TI  - Systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: an
      in vitro pulsatile flow study.
AB  - Hypertrophic cardiomyopathy, or HCM, is a relatively common disease which results
      in the hospitalization of more than 13,000 patients every year. It is
      characterized by a thickening of the interventricular septum and by systolic
      anterior motion, or SAM, of the mitral valve, which occurs when the distal tip of
      the mitral leaflets contacts the hypertrophied septum during systole and
      obstructs the left ventricular outflow tract. Using an in vitro pulsatile flow
      model of the left ventricle, the objective of the study was to investigate the
      relationship between the ventricular flow field and the mechanism of SAM and to
      specifically address the hypothesis that papillary muscle displacement can alter
      left ventricular flow patterns and create drag forces that can initiate SAM. Flow
      visualization revealed the presence in the ventricle of a large organized
      recirculation region throughout diastole. Besides maintaining the mitral leaflets
      close to the posterior wall, normally positioned papillary muscles also caused
      the diastolic vortex to help the mitral valve close near the posterior wall while
      simultaneously prepositioning the upcoming systolic outflow stream close to the
      septum, thereby minimizing the flow forces acting on the mitral valve. In
      contrast, the anterior displacement of the papillary muscles moves the entire
      mitral apparatus into the outflow tract. It also reverses the direction of the
      recirculating diastolic flows: The diastolic vortex now promotes the initiation
      of SAM by displacing the closing mitral leaflets anteriorly and by positioning
      the systolic outflow stream close to the posterior wall. These events lead to the
      creation of form drag forces as the systolic flow impacts the posterior side of
      the mitral leaflets, initiating SAM.

PMID- 7582156
TI  - In situ mitral valve stabilization with glutaraldehyde.
AB  - Mitral valve repair in the young rheumatic patient carries a high reoperation
      rate due to progression of the disease. In an attempt to halt or at least slow
      down this process, the possibility of fixing in situ the valve tissues with
      glutaraldehyde was explored. Six weanling sheep underwent tanning of their
      anterior mitral leaflet for two minutes with 0.5% buffered glutaraldehyde. The
      non-treated posterior mitral leaflet served as control. The animals were
      sacrificed at varying intervals between 2.5 and 6 months. At sacrifice, Doppler
      echocardiography and hemodynamic studies were done. The leaflets were subjected
      to histopathologic examination and calcium and glutaraldehyde contents were
      estimated. Glutaraldehyde treatment of the anterior leaflet caused thickening of
      the cusp and chordae associated with partial devitalization of its core tissue,
      partial loss of endothelium and intense fibrocellular reaction with abundant
      elastic fibers without altering its functional integrity. It did not induce
      calcification. There were no detectable levels of glutaraldehyde at explantation.
      The posterior mitral leaflets were normal. Although the absence of calcification
      and partial viability of the tissue are encouraging, it does not necessarily
      follow that this treatment would arrest progression of the underlying disease.
      This process may have clinical application in the future, but it is not yet
      recommended.

PMID- 7582157
TI  - Local intranasal immunotherapy with allergen in powder in atopic patients
      sensitive to Parietaria officinalis pollen.
AB  - Local Intranasal Immunotherapy (LII) is a new approach to the treatment of
      allergic rhinitis due to the pollen of Parietaria officinalis. The aim of this
      study was to verify the usefulness of LII and to determine the proper doses.
      Twenty adult patients all presenting a sensitization to the pollen of Parietaria
      officinalis were randomly divided into two groups: 15 received the treatment and
      five were the control group. Treatment started before the beginning of the
      pollinic season of Parietaria officinalis and continued during the season. The
      extract used was an active extract of macronized powder Parietaria officinalis
      pollen in increasing doses. Doses were determined periodically with specific
      nasal provocation tests. Results in the treated group compared to the control
      group were statistically significant if one considers the increase in threshold
      sensitivity in the nasal provocation test, the diminution of clinical
      symptomatology and the quantity of drug required to control symptoms in the
      treated group. The side effects were few; it was only in one case that the
      treatment had to be interrupted. LII for allergic rhinitis due to the pollen of
      Parietaria officinalis seems an effective and practicable method even during the
      pollinic season.

PMID- 7582158
TI  - Bronchial provocation with cat allergen: long-term outcome of the late allergic
      reaction and the individual IgE CRIE pattern.
AB  - In bronchial provocation tests with allergen, about 50% of the patients
      experienced a late allergic reaction (LAR), which has been associated with a
      specific IgE pattern as determined by crossed radioimmunoelectrophoresis (CRIE).
      Long-term outcome of this LAR is still unknown. Six patients allergic to cat,
      with documented LAR and specific IgE CRIE patterns were rechallenged in the same
      conditions after a mean interval of 2.5 years. Forced expiratory volume in one
      second (FEV1) and resistance results of the bronchial provocation tests (BPT)
      were compared, as well as specific IgE level and IgE CRIE patterns. All six
      patients were still suffering from asthma when exposed to a cat, although they
      were not being treated for asthma. Three patients (50%) had lost their LAR
      without specific treatment. They were older, with a longer history of asthma, but
      presented a very similar early allergic reaction to similar allergen doses. The
      other 3 were more reactive to the allergen but presented similar LAR after a
      slightly worse early allergic reaction (EAR). Specific IgE levels had decreased
      and the IgE CRIE pattern showed a diminished intensity of staining in the three
      patients who had lost their LAR, as opposed to the other three. These data
      suggest that asthmatic patients can lose their LAR over time without treatment.
      The occurrence of a LAR seems to be associated with a specific IgE CRIE pattern
      and IgE level. Further analysis of the individual antigen fractions might help to
      understand the mechanism of allergic reactions.

PMID- 7582159
TI  - Comparative studies of allergenic extracts prepared from freshly collected,
      dried, or dried and defatted pollen.
AB  - Fresh pollen samples of Parietaria judaica, Betula pubescens, Dactylis glomerata
      and Olea europaea were collected and aliquot portions of these pollens were
      stored after drying in hot air, while other portions were dried and then defatted
      with diethylether. The different pollen materials were extracted with aqueous
      media to obtain the non-dialyzable allergenic protein constituents. Review of the
      production data, together with comparative analyses of the UV-absorption spectra
      and of IgE binding potencies did not reveal appreciable differences in allergen
      composition among extracts of fresh, dried, or dried and defatted pollen
      materials. However, microscopic examination showed the fresh pollen to be no
      longer viable.

PMID- 7582160
TI  - Hyperresponsiveness to bronchoconstrictor agents in experimental animals treated
      with terbutaline and its effect on pancreatic beta cells.
AB  - Attempts have been made to obtain further experimental evidence in the
      development of hyperresponsiveness measured as mortality rate in terbutaline
      treated animals after the administration of carbachol in rats and ovoalbumin in
      sensitized guinea pigs. The dose of terbutaline chosen was approximately the dose
      an asthmatic patient might use in an attack, and its effect on pancreatic insulin
      synthesis was studied in rats since it has been suggested that insulin is a pro
      inflammatory hormone. Our results show that prolonged treatment with terbutaline
      increases the mortality from bronchoconstrictor stimuli. Increased levels of
      pancreatic insulin synthesis were also observed by immunocytochemical study
      carried out on pancreas from terbutaline-treated rats.

PMID- 7582162
TI  - Specific IgE determination using the CAP system: comparative evaluation with
      RAST.
AB  - The CAP system's main contribution is its solid phase, which consists of a
      cellulose polymer activated within a capsule (the ImmunoCAP). This solid phase
      can bind more protein to it, and, in addition, the conditions of reaction seem to
      make the system more sensitive at detecting antibodies to certain antigens. It is
      therefore important to assess the new analytical and diagnostic performance in
      comparison with previous systems. In this context, we studied the reliability and
      comparison with the RAST and with skin tests carried out on 144 pediatric
      patients. Skin tests and specific IgE for radioimmunological RAST (radio
      allergosorbent test) and for the fluoroimmunological CAP system were performed on
      all the patients. The RAST/CAP correlation quotients for the different allergens
      tested varied between 0.971 and 0.991. Diagnostic sensitivity increased for all
      the allergens studied and specificity remained unchanged. The system provides
      reliable results, with better diagnostic capacity than RAST, but it must be
      quantified for each allergen because its results are not interchangeable.

PMID- 7582161
TI  - Compensatory levels of salivary IgM anti-Streptococcus mutans antibodies in IgA
      deficient patients.
AB  - The protective role of salivary IgA in dental caries has not been completely
      demonstrated, so, in order to elucidate this point, we evaluated 15 totally and
      partially IgA-deficient children in terms of the following variables: dental
      caries indexes, bacterial plaques, number of Streptococcus mutans and
      Lactobacillus in the saliva, and titers of IgA, IgG and IgM anti-Streptococcus
      mutans antibodies in the saliva. Age-matched healthy children served as the
      control group. IgA-deficient children showed caries scores lower than those of
      the healthy children; in addition, no statistical difference was found between
      amount of dental plaque and numbers of the bacteria in saliva. The totally IgA
      deficient children presented IgM in levels much higher than the healthy children
      (p < 0.05). These data could indicate a compensation for the IgA deficiency by
      IgM.

PMID- 7582163
TI  - Platelet aggregation in IgE-mediated allergy with elevated soluble Fc epsilon
      RII/CD23 level.
AB  - In 25 house dust mite-sensitive patients with perennial allergic rhinitis, an
      analysis of platelet aggregation tests (dual-channel aggregometer, Chronolog
      Corp, 345 model) induced by adenosine diphosphate (ADP) was carried out. The
      levels of total serum IgE specific antibodies against Dermatophagoides
      pteronyssinus and the soluble form of the low affinity IgE receptor (sFc epsilon
      RII/sCD23) were estimated as well. The study was carried out in a dynamic state,
      before and after 2 years of treatment with specific immunotherapy. We observed a
      significantly diminished platelet aggregation response, which partially improved
      after treatment. The results of this study suggest that platelet
      hyporesponsiveness might be involved in the pathogenesis of house dust mite
      hypersensitivity.

PMID- 7582164
TI  - Study of sensitivity to the pollen of Fraxinus spp. (Oleaceae) in Cordoba, Spain.
AB  - The level of ash pollen grains (Fraxinus spp.) detected in the air in the city of
      Cordoba rarely surpasses the daily average of 8 g/m3 and is always detectable
      during the winter and the beginning of the spring. This fact, together with the
      knowledge of the presence of perennial symptoms in patients monosensitive to Olea
      in this area, allows us to suspect the possibility of cross-reactivity between
      both taxa. The skin tests carried out on a total of 1500 pollinotic patients with
      an extract of Fraxinus pollen offer us a global sensitization frequency of 59%.
      Furthermore, the Fx+ patients generally have a higher frequency of rural origin
      or they live in the most southerly district of the province. As for the age and
      sex of the patient, significant differences were found for the age groups between
      5-10 years and over 25 but the frequency for both sexes was equal. As for the
      clinical features, differences in the family and personal antecedents of atopy
      were not observed, although rhinoconjunctival clinical antecedents seemed to
      prevail slightly over asthma antecedents. In relation to the duration of the
      symptoms, the patients presented a long evolution in their symptomatology. The
      great majority of the patients were polysensitive; only 8% were found to be
      monosensitive, with unimportant differences in their evolution after
      immunotherapeutic treatment. On the other hand, 92% of the Fx+ patients presented
      reactions to Olea pollen (but only 41% of the Fx- patients did), whereas 62%
      showed sensitivity to Cupressus, marking a strong contrast with the Fx-patients,
      who all tested negative for Cupressus pollen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582165
TI  - Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives.
AB  - Two patients treated with parenteral paramethasone (Triniol) and dexamethasone
      (Sedionbel) are described. A few minutes after administration of the drugs, they
      presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The
      purpose of our study was to determine the cause of the patients' reactions, the
      immunological mechanisms involved and whether these patients would be able to
      tolerate any kind of corticoid. Clinical examinations and skin, oral and
      parenteral challenges with different corticosteroids and ELISA tests were
      performed. In the two patients, skin and ELISA tests with paramethasone were
      negative, as was the prick test with each of its excipients. A single-blind
      parenteral challenge with Triniol was positive in both patients after the
      administration of 1 ml of the drug, and negative with its excipients. We also
      carried out oral and parenteral challenges with other corticosteroids and found
      intolerance to some of them. These results suggest that paramethasone caused
      pseudoallergic reactions in our patients. Corticosteroids different from
      paramethasone also produced hypersensitivity reactions in these patients;
      however, a few of them were tolerated. The basic mechanisms of those reactions
      are not yet fully understood. To our knowledge, this is the first report of a
      pseudo-allergy caused by paramethasone.

PMID- 7582166
TI  - Extraction and purification of microbial DNA from petroleum-contaminated soils
      and detection of low numbers of toluene, octane and pesticide degraders by
      multiplex polymerase chain reaction and Southern analysis.
AB  - We investigated the use of multiplex polymerase chain reaction (PCR) techniques
      coupled with Southern analysis to detect xenobiotic-degrading organisms that had
      been added to three soils. Two soils highly contaminated with petroleum
      hydrocarbons and a less contaminated control soil were amended with tenfold
      dilutions of Pseudomonas putida mt-2 (pWW0), P. oleovorans (OCT), and Alcaligenes
      eutrophus JMP134 (pJP4), or, for controls, phosphate buffer alone. Total DNA was
      then isolated from the soils and purified using a sequential precipitation and
      dissolution purification procedure. This DNA was subjected to multiplex
      polymerase chain reaction (PCR) using primers that amplify regions of xylM (PCR
      product = 631 bp), alkB (546 bp) and tfdA (710 bp), which are found on pWW0, OCT
      and pJP4, respectively. The sizes of the amplified DNA fragments were designed to
      permit simultaneous amplification and detection of the target genes. Ethidium
      bromide-stained gels of the initial PCR reaction indicated detectable
      amplification of between 10(0) to 10(6) cells per gram soil, depending on the
      soil and the target gene. Southern analysis of the PCR amplified DNA improved
      detection limits to between 1 and 10 cells of each target species per gram of
      soil, and confirmed the identity of the PCR products. For some samples that were
      initially resistant to PCR, dilution of the environmental DNA resulted in
      positive PCR results. This treatment presumably overcame the inhibition of the
      PCR by diluting coextracted contaminants in the environmental DNA. A second PCR
      on an aliquot (1 microL) of the first reaction increased the ethidium bromide
      based detection limits for one of the soils to six cells per gram of soil; it did
      not increase the detection limits for the other soils. Therefore, the DNA
      extraction procedure and multiplex PCR permitted the simultaneous detection of
      three types of biodegradative cells, at a lower detection limit of approximately
      10 cells per gram of highly contaminated, organic soil. However, due to kinetic
      limitations of multiplex PCR, the amplified signals did not follow a close dose
      response to the numbers of added target cells.

PMID- 7582168
TI  - Genetic diversity within mer genes directly amplified from communities of
      noncultivated soil and sediment bacteria.
AB  - Individual merRT delta P regions were amplified from DNA directly isolated from
      soil and sediment samples using consensus primers derived from the conserved mer
      sequences of Tn501, Tn21 and pMER419. Soil and sediment samples were taken from
      four sites in the British Isles; one 'pristine' (SB) and three polluted (SO, SE,
      T2) with respect to mercury. The sizes of the PCR products amplified
      (approximately 1 kb) were consistent with their generation from mer determinants
      related to the archetypal elements found in Gram negative bacteria. Forty-five
      individual clones of sequences obtained from these four sites were isolated which
      hybridized (> 70% homology) to a merRT delta P probe from Tn501. The diversity of
      these amplified mer genes was analysed using Restriction Fragment Length
      Polymorphism (RFLP) profiling. Fourteen RFLP classes were distinguished, 12 of
      which proved to be novel and only two of which had been identified in an earlier
      study of 40 Gram negative mercury resistant bacteria cultured from the same four
      sites. UPGMA analysis was used to examine the relationships between the 22
      classes of determinant identified. The T2 site, which has the longest history of
      mercury exposure, was found to have the greatest level of diversity in terms of
      numbers of classes of determinant, while the SO site, which had the highest
      mercury levels showed relatively low variation. Variation of mer genes within and
      between the sequences from cultivated bacteria and from total bacterial DNA shows
      clearly that analysing only sequences from cultivated organisms results in a
      gross underestimation of genetic variation.

PMID- 7582169
TI  - Gene transfer from a bacterium injected into an aquifer to an indigenous
      bacterium.
AB  - Two novel 3-chlorobenzoate-degrading bacteria were previously isolated from an
      aquifer in which no such bacteria could be enriched prior to the introduction of
      the 3-chlorobenzoate-degrading strain, Pseudomonas sp. B13. To understand the
      origin of 3-chlorobenzoate-degrading genes in the two novel isolates, the 16S
      ribosomal RNA, clcD (dienelactone hydrolase) and clcA (chlorocatechol oxygenase)
      genes from these bacteria were amplified and sequenced. The partial 16S rRNA gene
      sequences and REP-PCR patterns showed that these two novel isolates were
      identical but differed from strain B13. Phylogenetic analyses revealed that the
      novel isolates were closely related to Alcaligenes eutrophus in the beta subclass
      of the Proteobacteria, whereas strain B13 was related to Pseudomonas aeruginosa
      and P. mendocina in the gamma subclass of the Proteobacteria. In contrast, the
      clcD and clcA gene sequences were identical on strain B13 and these two isolates,
      indicating that the 3-chlorobenzoate-degrading genes were transferred from strain
      B13 to these isolates. What cannot be established is when this transfer occurred.

PMID- 7582170
TI  - DNA-based monitoring of total bacterial community structure in environmental
      samples.
AB  - Determining the structure of bacterial communities and their response to stimuli
      is key to understanding community function and the interactions that occur
      between micro-organisms and the environment. However, bacterial communities often
      comprise complex assemblages of large numbers of different bacterial populations.
      An approach is presented which allows bacterial community structure to be
      determined by fractionation of the complex mixture of total bacterial community
      DNA using the DNA-binding dye bisbenzimidazole which imposes G+C-dependent
      changes in the buoyant density of DNA. Bacterial community structure presented as
      percentage of total DNA vs. percentage G+C content of DNA is an indication of the
      relative abundance of phylogenetic groups of bacteria. Changes in the composition
      of a soil bacterial community in response to perturbations in the form of carbon
      amendment and altered water status were monitored.

PMID- 7582167
TI  - The phylogenetic distribution of a transposable dioxygenase from the Niagara
      River watershed.
AB  - Horizontal gene transfer in the Bacteria has been demonstrated to occur under
      natural conditions. The ecological impact of gene transfer events depends on the
      new genetic material being expressed in recipient organisms, and on natural
      selection processes operating on these recipients. The phylogenetic distribution
      of cbaAB genes for chlorobenzoate 3,4-(4,5)-dioxygenase, which are carried within
      Tn5271 on the IncP beta plasmid pBRC60, was investigated using isolates from
      freshwater microcosms and from the Niagara River watershed. The latter included
      isolates from surface water, groundwater and bioremediation reactor samples. The
      cbaAB genes have become integrated, through interspecific transfer, primarily
      into species of the beta Proteobacteria (44/48 isolates). Only four isolates,
      identified as Pseudomonas fluorescens (3/48) and Xanthomonas maltophilia (1/48),
      belonged to the gamma Proteobacteria, despite the observation that pBRC60 was
      capable of mobilizing these genes into a wide range of beta and gamma
      Proteobacteria in the laboratory. The natural host range correlated with the
      distribution of the meta-ring-fission pathway for metabolism of protocatechuates
      formed when the cbaAB genes were expressed (45/48 isolates). We proposed the
      hypothesis that natural selection has favoured recipients that successfully
      integrate the activity of the transferred dioxygenase with the conserved meta
      ring-fission pathway. The hypothesis was tested by transferring a plasmid
      construct containing the cbaAB genes into type strains representative of the beta
      and gamma Proteobacteria. The concept of applying mobile catabolic genes to probe
      the phylogenetic distribution of compatible degradative pathways is discussed.

PMID- 7582171
TI  - Spatial analysis of nuclear and mitochondrial RFLP genotypes in populations of
      the chestnut blight fungus, Cryphonectria parasitica.
AB  - Spatial structure of both nuclear and mitochondrial RFLPs were studied in several
      populations of the chestnut blight fungus, Cryphonectria parasitica, using a
      variety of spatial autocorrelation tests designed to detect nonrandom patterns.
      Fungal individuals were sampled from cankers on infected chestnut trees, and the
      location of each tree was mapped. Single-locus nuclear RFLPs, nuclear
      fingerprints, and mitochondrial DNA haplotypes were determined for each
      individual. Individuals with the same DNA fingerprint genotypes occurred closer
      together than would be expected at random in four of the five plots, while
      mitochondrial DNA haplotypes were aggregated in all five plots. Genetic distances
      between individuals, expressed as one minus the proportion of shared restriction
      fragment size classes for fingerprints and mitochondrial haplotypes, were
      significantly correlated with Euclidean distances between individuals in four of
      the five populations, but these correlations were very weak (r < 0.18). The same
      DNA fingerprint and single-copy nuclear RFLP alleles occurred on the same trees
      or immediately neighbouring trees more often than would be expected at random.
      Most of the aggregation for all three genetic markers occurred among individuals
      within the same cluster of chestnut stems or on neighbouring trees. Lack of
      spatial autocorrelation in one population was probably due to sampling on a
      larger scale that was too coarse to detect any patterns. Significant aggregation
      of genotypes in C. parasitica is most likely caused by some degree of restricted
      dispersal within populations. The implications of restricted dispersal are
      discussed in relation to the breeding system and isolation by distance in
      populations of C. parasitica.

PMID- 7582172
TI  - Palliative care for children.

PMID- 7582173
TI  - Models of care for children dying of malignant disease.
AB  - Two-thirds of children with cancer are now cured of their disease. For the
      majority of the remainder there is a period of terminal care. The emphasis of
      care at this stage is on the quality of life for both child and family. Most
      families prefer that their child should be cared for at home, with professional
      support from those known to them. This paper looks at various approaches to
      terminal care in children and describes the model of care for such children in
      the south west of the United Kingdom. From this information, key elements of an
      effective service are identified.

PMID- 7582174
TI  - The death of a twin.
AB  - Death or disability is much more common in multiple births than single children,
      especially in the perinatal period. Parents face particular problems in that
      their loss may be underestimated; their grieving may be impeded by the confusion
      between the live and the dead baby, and the constant reminder in the survivor may
      be painful. The surviving twin often suffers profoundly from the loss and may
      need lifelong support. The value of the twinship should always be respected.

PMID- 7582175
TI  - The changing face of paediatric oncology.
AB  - Childhood malignancies differ from those encountered in adult life not only in
      tumour type but also in their response to treatment. There have been major
      advances in the use of combined modality and combination chemotherapy regimens
      over recent years. High-dose therapy with bone marrow and peripheral stem cell
      transplantation procedures are being increasingly incorporated into specialized
      treatment regimens, particularly in the management of 'high-risk' and relapsed
      patients who were previously incurable. Overall, cure rates for children with
      cancer now exceed 60%. Despite this, the progress in the treatment of some tumour
      groups remains poor. This paper summarizes recent advances but also highlights
      some of the problem areas that still exist or are expected to be encountered in
      the near future.

PMID- 7582176
TI  - Respiratory symptoms in children dying from malignant disease.
AB  - Shortness of breath and other respiratory symptoms frequently complicate the
      symptomatic management of terminally ill adults. The extent of the problem in
      children is not known, but anecdotal evidence from nurses and physicians
      experienced in paediatric oncology has suggested that respiratory problems are
      less frequent in children dying from malignant disease than in adults. This is a
      retrospective review of all children dying from cancer under the care of the
      symptom care team at the Royal Marsden Hospital between 1982 and 1993. The
      results show that respiratory symptoms were recorded during the last three months
      of life in 40% of analysable case histories. The nature of respiratory symptoms
      in paediatric cancer patients is discussed.

PMID- 7582177
TI  - The McGill Quality of Life Questionnaire: a measure of quality of life
      appropriate for people with advanced disease. A preliminary study of validity and
      acceptability.
AB  - This is the first report on the McGill Quality of Life Questionnaire (MQOL), a
      questionnaire relevant to all phases of the disease trajectory for people with a
      life-threatening illness. This questionnaire differs from most others in three
      ways: the existential domain is measured; the physical domain is important but
      not predominant; positive contributions to quality of life are measured. This
      study was conducted in a palliative care setting. Principal components analysis
      suggests four subscales: physical symptoms, psychological symptoms, outlook on
      life, and meaningful existence. Construct validity of the subscales is
      demonstrated through the pattern of correlations with the items from the Spitzer
      Quality of Life Index. The importance of measuring the existential domain is
      highlighted by the finding that, of all the MQOL subscales and Spitzer items,
      only the meaningful existence subscale correlated significantly with a single
      item scale rating overall quality of life.

PMID- 7582178
TI  - Rehydration in palliative and terminal care: if not--why not?
AB  - Patients who are in the last few days of life are often too frail to take oral
      fluids and nutrition. This may be due entirely to the natural history of their
      disease, although the use of sedative drugs for symptom relief may contribute to
      a reduced level of consciousness and thus a reduced oral intake. Rehydration with
      intravenous (i.v.) fluids is the usual response in acute care settings, whereas
      the hospice movement has often argued against this approach. The issues are
      complex and involve not only physical, psychological and social concerns, but
      also ethical dilemmas. A review of the literature gives conflicting reports of
      the physical discomfort that may be attributed to dehydration in dying patients.
      There are many confounding variables, including the concomitant use of
      antisecretory drugs, mouth breathing and oral infection. It remains unproven
      whether i.v. fluids offer symptomatic relief in this situation. Hospice doctors
      are concerned that the use of i.v. fluids gives confusing messages to relatives
      about the role of medical intervention at this stage in a patient's illness. A
      drip may cause a physical barrier between a patient and their loved one at this
      important time. The use of other methods of fluid replacement are discussed. In
      the absence of definitive research in this area, the balance of the burdens and
      benefits of such treatment remains subjective. The prime goal of any treatment in
      terminal care should be the comfort of the patient. Decisions should be made on
      an individual basis, involving both patients and their carers wherever possible.
      Prolonging life in such circumstances is of secondary concern and i.v. fluids
      given in this context may be futile. The ethical dilemmas of withholding and
      withdrawing medical treatment in addition to those of conducting research in this
      area are discussed.

PMID- 7582179
TI  - A regional survey of opioid use by patients receiving specialist palliative care.
AB  - A study was conducted to determine the patterns of opioid use in patients under
      the care of specialist palliative care (SPC) teams in Trent Region, both in the
      community and in inpatient settings. The design was a survey of point prevalence
      by case note and drug chart review. The case notes and prescription records of
      1007 patients were reviewed, and data collected on age, sex, diagnosis, date of
      referral, care settings, opioid form and dose on referral, and most recent opioid
      form and dose. Nine hundred and seventy patients had cancer; their ages ranged
      from 18 to 98 years (mean 66.5; median 69). Care was delivered by community
      specialist nurse for 39%, hospice daycare (DC) for 31%, hospice based homecare
      for 11%, hospice inpatient unit (IPU) for 15%, hospice outpatient (OP) for 5%,
      and other for 0.5%. There was no record of medication in 2% of the notes. No
      opioids had been prescribed for 43% of patients (range 24% IPU to 49% DC), 10% of
      patients were using weak opioids only (range 0.9% IPU to 16% OP), and 45% of
      patients were using strong opioids (range 39% DC to 75% IPU), the majority being
      on morphine (87% of total strong opioids). Daily oral morphine equivalence (OME)
      dosages ranged form 0.4 mg to 3600 mg (mean 166; median 60; mode 60). Dose
      changes under SPC ranged from -780 mg to +3900 mg OME, 42% patients having had no
      change in their dosage and 15% having reduced their opioid dose whilst under SPC.
      This survey challenges the popular impression that patients receiving SPC require
      large doses of morphine. The highest prevalence of potent opioid prescribing was
      in hospice IPUs, largely owing to the use of parenteral diamorphine. Conversely,
      IPUs had the lowest prevalence of weak opioids. Staff caring for patients with
      cancer must consider the need for downward as well as upward titration of opioid
      dosages.

PMID- 7582180
TI  - An extra care sheltered housing complex for frail ambulant cancer patients.
AB  - The history and development of an extra care sheltered housing complex,
      specifically designed and built for frail, ambulant, cancer patients is reviewed.
      Consideration is given to diagnosis, length of stay, place of death, family and
      social background. Problems are highlighted and the need for future research is
      discussed.

PMID- 7582184
TI  - The impact on community palliative care services of a hospital palliative care
      team.

PMID- 7582183
TI  - Comparative cost of hyoscine injections.

PMID- 7582181
TI  - Nurses in private nursing homes: a study of their knowledge and attitudes to pain
      management in palliative care.
AB  - Nurses working in private nursing homes may not have the same degree of access to
      support and education in palliative care as nurses in NHS 'care of the elderly'
      wards. A study was conducted comparing two groups of nurses working in these two
      environments in one health district. Twenty-four nurses underwent semistructured
      interviews focusing on pain management. Both groups showed equal enthusiasm for
      their work with elderly patients. However, those from the care of the elderly
      wards were able to offer many more treatment strategies to relieve pain than
      their colleagues from the private nursing homes. The study uncovered a sense of
      isolation and a lack of postbasic education opportunities for nurses outside the
      NHS. If this small local study reflects a national trend, then there are major
      implications for the educational activities of palliative care teams.

PMID- 7582182
TI  - Topical ophthalmic anaesthesia for severe facial pain due to recurrent head and
      neck carcinoma.

PMID- 7582185
TI  - Basic principles associated with gene therapy of cancer.
AB  - Advances in gene delivery systems have made possible the development of
      strategies to eradicate cancers via genetic manipulation. Although the strategy
      of 'gene therapy' remains in its infancy, experimental tumour models have
      produced encouraging results and have demonstrated that tumour growth or
      development can be altered by genetic manipulations. Investigators are hopeful
      that current and future human trials will confirm the role of these modalities in
      cancer treatment. This review focuses on several aspects of gene therapy that
      provide clinicians with a framework to understand the rationale and basic
      principles underlying current gene therapy protocols being conducted for cancer
      treatment. The relative merits of different gene delivery systems and the
      mechanisms underlying clinical gene therapy strategies are reviewed. In addition,
      we discuss the relevance of these new techniques to the oncologic surgeon.

PMID- 7582186
TI  - Chemotherapy of human small-cell gastrointestinal carcinoma xenografts in nude
      mice.
AB  - We established two xenografts of small-cell carcinoma (SCC) arising in the
      oesophagus or the stomach, designated TEG13 and TSG15, and investigated the
      responses to experimental chemotherapy on these strains. Both tumours were
      classified as the intermediate cell type of SCC composed of small cells having
      neuroendocrine features in terms of morphology, argyrophil property, and
      immunoreactivity for neuron-specific enolase. Mitomycin C, cisplatin, and
      cyclophosphamide were judged to be effective against both strains. Particularly,
      cisplatin produced almost complete regression of tumour growth of the TEG13
      strain. Etoposide proved effective only against the TSG15 strain. Moreover, the
      combined treatment with etoposide and cisplatin produced the most pronounced
      antitumour effect against the TSG15 strain. These studies suggest that cisplatin
      may be a key drug for chemotherapy of oesophageal SCC, and etoposide plus
      cisplatin treatment may be especially recommended in the treatment of gastric
      SCC. Mitomycin C should be re-evaluated in gastrointestinal SCC.

PMID- 7582187
TI  - Toxicity study of hepatic artery infusion chemotherapy with massive dose FUDR in
      rats.
AB  - Hepatic artery infusion (HAI) of fluoroudeoxyuridine (FUDR) has been shown to be
      effective in the treatment of liver metastases from colorectal cancer. However,
      local toxicity is the most serious limitation of this therapy. The aetiology of
      HAI toxicity remains unclear. To assess the HAI toxicity, forty-eight non-tumour
      bearing, healthy BD-IX rats were randomized to control or treatment groups. The
      control group (n = 24) received heparinized saline alone (200 u heparin kg-1 day
      1) and the treatment group (n = 24) received 6.7 mg FUDR kg-1 day-1 (equivalent
      to the human dose of 1.0 kg-1 day-1) via HAI for 28 days. Blood samples were
      collected for haematologic and biochemical analysis twice a week (on days 3 and
      7). Toxicity was evaluated by determination of mortality, body weight, white
      blood cell (WBC) count, serum glutamic oxaloacetic transaminase (SGOT), alkaline
      phosphatase (ALP), total bilirubin and blood urea nitrogen (BUN), and creatinine.
      No significant differences in WBC, SGOT, BUN and creatinine levels were found
      between the group receiving FUDR treatment and the control group. Significantly
      higher total bilirubin levels, mortality and body weight loss were found in the
      FUDR-treated group than in the control group. A multivariate analysis revealed
      that total bilirubin level was the only significant predictor of mortality in the
      FUDR treatment group. These results suggested that biliary tract damage seems to
      be the principal toxicity of HAI FUDR chemotherapy.

PMID- 7582188
TI  - p53 and disease progression in patients with non-small cell lung cancer.
AB  - Present methods of predicting nodal progression preoperatively in patients with
      non-small cell lung cancer (NSCLC) are inadequate. Our hypothesis was that p53
      expression in primary NSCLC would predict disease progression, making it a useful
      marker of adverse outcome. From 1987 to 1992, sixty-eight consecutive NSCLC
      patients underwent potentially curative lung resection and mediastinal lymph node
      dissection by one surgeon. Primary tumours were analysed using the p53 monoclonal
      antibody 1801. p53 overexpression was found in 53% of tumours. p53 expression did
      not correlate with age, gender, histology or stage. A trend toward a higher
      incidence of p53 expression was seen in tumours with nodal spread (P = 0.06), and
      p53 expression correlated significantly (P = 0.03) with improved disease-free
      survival in patients with squamous cell carcinoma (SCC). p53 was the fourth most
      important independent predictor of survival, behind histology, gender and nodal
      disease. As a weak independent predictor of survival, the correlation of p53
      expression with survival in patients with SCC must be evaluated with caution. If
      borne out in a larger patient population, p53 expression may be a marker of nodal
      disease progression in patients with NSCLC.

PMID- 7582190
TI  - Neutrophil hyper-reactivity after exercise-induced angina pectoris.
AB  - BACKGROUND: Previous studies have suggested an increased risk of myocardial
      infarction associated with physical exercise. Activated neutrophils may
      contribute to the triggering mechanisms. METHODS: Fifteen patients with stable
      angina pectoris underwent symptom-limited bicycle ergometry. In neutrophils
      obtained from serial blood samples, superoxide anion production (SOP) was
      determined by superoxide dismutase-inhibited reduction of cytochrome C and
      chemotactic mobility in the microchemotaxis chamber. The same ergometry was
      repeated after successful balloon angioplasty [percutaneous transluminal coronary
      angioplasty (PTCA)]. RESULTS: Rate-pressure products and systemic lactate
      concentrations were similar in both ergometries. Angina was induced in all
      exercise tests before PTCA, but in none after PTCA. Before the ergometries,
      systemic neutrophil counts, SOP and chemotactic mobility were essentially the
      same. Compared with baseline, exercise-induced angina immediately after the first
      ergometry was associated with an increase in neutrophil count by 0.8 +/- 0.1 nl-7
      (P < 0.01), an increase in N-formyl-methionyl-leucyl-phenylalanine (FMLP)
      stimulated SOP by 2.44 +/- 0.49 nmol/15 min/5000 cells (P < 0.01) and an increase
      in chemotaxis by 10.28 +/- 1.65 cells per vision field (P < 0.01). In the
      ergometry after PTCA this increase in SOP and in chemotaxis disappeared (0.26 +/-
      0.39 nmol/15 min/5000 cells and 2.15 +/- 1.52 cells per vision field; NS),
      whereas the increase in neutrophil count was not significantly different from
      that in the ergometry before PTCA. CONCLUSION: This study reveals that neutrophil
      hyper-reactivity after exercise-induced angina can be attributed to myocardial
      ischaemia.

PMID- 7582189
TI  - The value of p53 and Ki67 as markers for tumour progression in the Barrett's
      dysplasia-carcinoma sequence.
AB  - In the Barrett's oesophagus (BE) progression from metaplasia, via dysplasia, into
      invasive cancer, an aberrant cell proliferation governed by genetic change plays
      a central role. Alterations of the p53 tumour-suppressor gene appear especially
      critical and, like the proliferation marker Ki67, can be detected by
      immunohistochemistry. The purpose of this study therefore was to investigate the
      clinical value of p53 and Ki67 as markers for tumour progression in BE, and at
      the same time test the validity of the concept of a metaplasia-dysplasia
      carcinoma sequence in BE by correlating the expression of these markers with
      various grades of dysplasia. Thirty-two lesions (seven negative for dysplasia,
      five indefinite for dysplasia, 11 low-grade dysplasia and nine high-grade
      dysplasia) from 25 archival resection specimens were selected for study.
      Increasing grades of dysplasia showed increasingly p53 accumulation; p53
      accumulation was never observed in mucosa without dysplasia. The increasing p53
      expression was accompanied by an increased Ki67-labelling index and an upward
      shift of the proliferative compartment. The results lend support to the multistep
      progression model of a metaplasia-dysplasia-carcinoma sequence in BE. Expression
      of p53 and Ki67, markers which can be easily applied on archival material, can be
      valuable adjuncts for the histopathological diagnosis of dysplasia and may have
      predictive value for cancer risk.

PMID- 7582191
TI  - Coronary sinus endothelin-1 concentrations after cardioplegic cardiac arrest.
AB  - BACKGROUND: Data from animal experiments demonstrate that endothelin-1 is
      released into the coronary circulation during myocardial ischaemia and
      reperfusion, indicating that endothelin-1 may contribute to the pathophysiology
      of ischaemia and reperfusion. The aim of this study was to investigate the
      release of endothelin-1 into the coronary circulation during reperfusion of the
      human heart after hypothermic cardioplegic cardiac arrest. METHODS: Endothelin-1
      was measured in arterial, central venous and coronary sinus blood in 19 patients
      undergoing elective uncomplicated coronary artery bypass grafting before aortic
      crossclamping and 1, 5, 10 and 20 min after aortic declamping. RESULTS:
      Endothelin-1 concentrations showed a slight non-significant increase over
      baseline values 1, 5, 10 and 20 min after aortic declamping. Endothelin-1
      concentrations were not significantly higher in coronary sinus blood than in
      arterial blood at any time point measured, indicating no net release of
      endothelin-1 by the heart. CONCLUSIONS: Our results did not demonstrate
      endothelin-1 release into the coronary circulation after myocardial ischemia and
      reperfusion associated with hypothermic cardioplegic cardiac arrest.

PMID- 7582192
TI  - Rapid accurate diagnosis of acute myocardial infarction in patients with non
      traumatic chest pain within 1 h of admission.
AB  - BACKGROUND: Accurate diagnosis of impending acute myocardial infarction (AMI) in
      patients presenting at an emergency department with acute chest pain is essential
      for proper triage and treatment. We have developed an algorithm for the early
      diagnosis of AMI. METHODS: The diagnostic performances of ECG, creatine kinase
      (CK) and creatine kinase isoenzyme MB (CKMB) activities, CKMB mass, myoglobin,
      and cardiac troponin T (cTnT) were compared for early diagnosis of AMI in 60 non
      traumatic chest pain patients (22 AMI, 29 unstable angina, nine other diseases)
      on presentation to an internal medicine emergency department and 1 h thereafter.
      The classification and regression trees method was used for data analysis and
      revealed the following results. RESULTS: In patients with electrocardographic
      signs of acute transmural myocardial ischaemia on admission (mostly regional ST
      segment elevations), biochemical markers could not improve the diagnostic
      accuracy either on admission or 1 h later. By contrast, in patients with non
      diagnostic ECG, CKMB mass concentration measured 1h after admission was the best
      discriminator between AMI and non-AMI patients (discriminator value 5.8
      micrograms/l) and was superior to ECG and all other biochemical markers tested.
      This algorithm for diagnosing AMI is characterized by 96% sensitivity, 90%
      specificity, 84% positive predictive value, 97% negative predictive value, 92%
      accuracy, 0.05 negative likelihood ratio, and 9.1 positive likelihood ratio.
      CONCLUSION: The classification procedure obtained allows accurate rapid and early
      diagnosis of AMI and could therefore be a valuable diagnostic aid to physicians
      of emergency medicine.

PMID- 7582193
TI  - ST-segment/heart rate loop analysis on treadmill exercise testing can provide
      diagnostic and prognostic information in patients with stable effort angina.
AB  - BACKGROUND: In the assessment of myocardial ischemia and its severity using
      treadmill exercise testing (TMET), the magnitude of ST-segment depression is
      conventionally used. It is often difficult to distinguish false-positive from
      true ST-segment depression and to assess the severity of coronary artery disease
      (CAD). The purpose of the present study was to assess the ability of ST
      segment/heart rate loop (ST/HR loop) analysis to provide diagnostic and
      prognostic information in patients with stable effort angina. METHODS: ST/HR loop
      analysis was studied in 118 patients with stable effort angina without previous
      myocardial infarction who were taking medication. ST/HR loop patterns were
      classified into four types: type A (n = 38), simple clockwise rotation; type B (n
      = 34), clockwise rotation with quick ST recovery in the first half; type C (n =
      21), ST-segment depression that recovered at a constant rate; and type D (n =
      25), simple counter-clockwise rotation. The control group consisted of 40
      patients who had no ST-segment depression but were proved to have significant
      stenosis on coronary angiography. The ST/HR loop types were compared with (1) the
      conventional TMET parameters, (2) findings of coronary angiography, (3) severity
      of ischemia evaluated by exercise thallium-201 myocardial single-photon emission
      computed tomography (exercise TI-201 myocardial SPECT), and (4) short-term
      prognosis by follow-up study. RESULTS: The value of the simple heart-rate
      adjusted ST-segment depression index (delta ST/HR index) in the type A group (6.1
      +/- 5.8 microV/bpm) was higher (P < 0.05) than in the type C and D groups (2.7 +/
      2.0 microV/bpm and 1.7 +/- 1.2 microV/bpm, respectively). In the type A group,
      68% of the patients had multiple diseased coronary arteries. In the type D group,
      88% of the patients had either no significant coronary artery stenosis or
      significant stenosis in a single coronary artery. The ischemic size calculated by
      exercise TI-201 myocardial SPECT was higher (P < 0.05) in the type A group (47.6
      +/- 24.6%) than in the type B, C, and D groups (21.4 +/- 16.6%, 14.9 +/- 15.8%
      and 7.8 +/- 7.4%, respectively). During the follow-up study nine cardiac events
      occurred in the type A group, three in the type B group, and one in the type C
      group. The prognosis of the type A patients was significantly worse than that of
      the type D and control patients (P < 0.01). CONCLUSION: We conclude that the
      ST/HR loop analysis is a simple and useful parameter for providing diagnostic and
      prognostic information for patients with stable effort angina.

PMID- 7582199
TI  - Bibliography of the current world literature.

PMID- 7582194
TI  - Assessment of effects of intravenous dipyridamole on regional myocardial
      perfusion in children with Kawasaki disease without angiographic evidence of
      coronary stenosis using positron emission tomography and H2(15)O.
AB  - BACKGROUND: Positron emission tomography and H2(15)O were used to characterize
      regional myocardial blood flow and distribution at rest and in response to
      dipyridamole in children with Kawasaki disease but without angiographic evidence
      of coronary stenosis. METHOD: Patients were classified into two groups on the
      basis of the results of selective coronary angiography: subjects in group I had
      normal coronary angiograms (n = 4): subjects in group II had aneurysms (n = 5).
      RESULTS: Myocardial perfusion, assessed with H2(15)O, was homogeneous over all
      regions at rest and at peak flow in groups I and II. Dipyridamole infusion
      significantly reduced myocardial perfusion reserve in group II (average 3.56 +/-
      1.03 fold versus 5.06 +/- 1.37 fold in group I, P < 0.001). CONCLUSION: Our
      results suggest that aneurysms associated with Kawasaki disease may reduce
      myocardial reserve. Non-invasive quantitative assessment of myocardial blood flow
      with positron emission tomography and H2(15)O was useful in assessing the
      functional capacity of coronary artery lesions and the extent of myocardial
      damage in children with Kawasaki disease.

PMID- 7582201
TI  - Second-order analysis of space-time clustering.
AB  - We consider the problem of detecting and describing space-time interaction in
      point process data. We extend existing second-order methods for purely spatial
      point process data to the spatial-temporal setting. This extension allows us to
      estimate space-time interaction as a function of spatial and temporal separation,
      and provides a useful reinterpretation of a popular test, due to Knox, for space
      time interaction. Applications to simulated and real data indicate the method's
      potential.

PMID- 7582197
TI  - Influence of surface texture and charge on the biocompatibility of endovascular
      stents.
AB  - BACKGROUND: The mechanical behaviour and the surface characteristics of
      endovascular stents are key factors determining stent patency. In-vitro studies
      have suggested that surface texture and charge alter the biocompatibility of
      metallic stents. In this study, the influence of surface texture and charge of
      metallic stents on thrombosis and neointima formation was evaluated in a rabbit
      model. METHODS: Twenty-four stainless steel Palmaz-Schatz stents were coated
      either by an electrochemical deposition of metal on the stent surface or were
      coated with a metallic film which was implanted into the stent surface by argon
      ion bombardment. The coatings consisted of platinum, gold, or copper. Coated and
      uncoated control stents were implanted in rabbit iliac arteries. As
      antithrombotic therapy, 500 IU heparin and 60 mg aspirin was given intravenously
      before stent implantation, followed by 60 mg aspirin intravenously every third
      day for 4 weeks. Thrombus and neointima formation in arterial cross-sections of
      24 coated stents were compared with 19 uncoated stents using quantitative,
      computer-assisted histomorphometry and transmission electron microscopy. RESULTS:
      A higher stent surface porosity and more surface cracks after stent expansion
      were found after galvanization than after ion implantation. The in-vitro surface
      potentials of uncoated steel, copper-, and gold-coated or platinized stents were
      +150, +120, +180, and +180 mV, respectively. Four weeks after implantation, six
      of 14 galvanized stents, but none of the uncoated or ion bombarded stents, were
      occluded by a thrombus. Neointimal hyperplasia was increased in stents coated by
      galvanization compared with stents coated by ion implantation. In both study
      groups, the most electropositive coating (platinum or gold) induced markedly less
      neointima formation than the least electropositive (copper). CONCLUSION: Stent
      surface texture was the most important factor determining biocompatibility of
      coated Palmaz-Schatz stents in this study. In contrast to suggestions derived
      from in-vitro studies, the charge of stents does not seem to play a major role
      with respect to stent thrombogenicity. Low stent charge correlates with an
      increased neointima formation.

PMID- 7582200
TI  - The application of multidimensional scaling methods to epidemiological data.
AB  - This paper illustrates the use of multidimensional scaling methods (MDS) to
      examine space-time patterns in epidemic data. The paper begins by outlining the
      principles of MDS. The model is then formally specified and illustrated by
      application to two data sets. The first is partly a tutorial example. It uses
      monthly reported measles morbidity data for the 31-year period from January 1960
      to December 1990, collected for the 50 states of the USA, plus New York City and
      the District of Columbia. These data are used to explore the various ways in
      which MDS may be used to identify changing spatial patterns in geographically
      coded data. In addition to their tutorial use, the data are also employed to
      search for any substantive changes in the geographical structure of measles
      epidemics in the USA that may have followed the introduction of mass vaccination
      in 1965. New England appears to have developed an epidemic profile distinct from
      the rest of the USA, and there is tentative evidence of an urban-rural split in
      epidemic characteristics. The second data set takes annual reported measles
      mortality data for New Zealand and the states of Australia from 1860 to 1949. MDS
      is used to show how the spatial relationships among these geographical units have
      changed over time in response to changes in the sizes of local susceptible
      populations.

PMID- 7582195
TI  - Influence of patient sex and clinical history on working capacity and myocardial
      ischemia after coronary artery bypass surgery.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is generally accepted as
      effective in relieving patients from angina pectoris, and in improving survival
      in subgroups. However, subset evaluations of myocardial ischemia and exercise
      capacity after CABG are scarce. The aim of this study was to determine the
      outcome of CABG in terms of exercise capacity and stress ECG findings in
      subgroups of patients. METHODS: A stepwise bicycle exercise ECG (in most cases
      computerized) was performed on 362 patients within 1 year before and 2 years
      after CABG. RESULTS: Exercise capacity increased from a median value of 90 to 130
      W (P < 0.0001), more marked (P < 0.0001) in men (100-140 W) than in women (75-90
      W). Improvement was not significantly related to age. Occurrence of ST-segment
      depression at exercise decreased, 76% showing ST-segment depression of at least 1
      mm before the operation and 35% (P < 0.0001) 2 years after. Exercise-induced
      signs of ischemia on ECG did not differ between men and women. Maximum heart rate
      increased from a median value of 109 to one of 133 beats/min (P < 0.0001), and
      maximum systolic blood pressure from 170 to 210 mmHg (P < 0.0001). Termination of
      exercise because of chest pain decreased from 48 to 6% (P < 0.0001). Most subsets
      of patients improved exercise capacity with a reduction of ST-segment depression
      irrespective of their previous history and manifestations of cardiovascular
      disease. CONCLUSIONS: CABG caused a marked increase in exercise capacity and
      reduced signs of myocardial ischemia. Although men increased their working
      capacity by a greater extent than women, reduction in signs of myocardial
      ischemia was similar in both sexes.

PMID- 7582198
TI  - Characterization of platelet activation and thrombin generation accompanying
      percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: Despite anticoagulant therapy, intracoronary thrombus formation can
      accompany or be induced by percutaneous transluminal coronary angioplasty (PTCA).
      Clinical trials for the assessment of the efficacy of novel prophylactic regimens
      are expensive and difficult. Accordingly, we sought to develop an approach for
      investigating thrombogenesis accompanying PTCA that would facilitate the
      assessment of protective regimens in a relatively small number of patients.
      METHODS: Markers of in-vivo generation and activity of thrombin with plasma
      fibrinopeptide A (FPA) and platelet degranulation with beta-thromboglobulin (BTG)
      were measured in coronary sinus blood in patients undergoing PTCA. In an initial
      pilot study, we obtained peripheral venous blood samples through heparin-bonded
      sampling catheters to determine whether sampling affected values of the markers
      measured. We then measured FPA and BTG in coronary sinus blood samples, obtained
      from patients undergoing coronary angiography, to define the effects of
      injections of contrast media. Subsequently, we studied nine patients undergoing
      elective PTCA. Coronary sinus FPA and BTG were measured serially under baseline
      conditions during and after the procedure. RESULTS: The catheters used elicited
      negligible effects on FPA and BTG values over a 30 min sampling interval.
      Similarly, coronary angiography had no detectable effect on coronary sinus FPA
      and BTG values. PTCA did not increase FPA (mean value at the conclusion of PTCA
      1.17 +/- 0.31) or BTG (mean 30.9 +/- 15.9) in the PTCA group as a whole. However,
      in one patient the values increased markedly. For two patients, baseline values
      were elevated but declined with the re-establishment of brisk coronary flow after
      successful PTCA. CONCLUSIONS: We have shown that coronary sinus samples can be
      obtained under conditions permitting assessment of ongoing thrombosis in patients
      undergoing PTCA. Samples can be obtained without introduction of artifactual
      elevations of FPA or BTG, facilitating assessment of the efficacy of novel
      antithrombotic regimens in preventing thrombogenesis otherwise seen in an
      important minority of patients undergoing coronary interventions.

PMID- 7582196
TI  - Effect of cilazapril on vascular restenosis after percutaneous transluminal
      coronary angioplasty.
AB  - BACKGROUND: In experimental studies using cilazapril, the strongest inhibition of
      neointima formation was obtained when treatment was initiated 6 days before
      injury. The MERCATOR trial showed no reduction in restenosis with cilazapril
      given after percutaneous transluminal coronary angioplasty (PTCA). The purpose of
      this study is to determine whether previous administration of cilazapril could
      prevent restenosis. METHODS: A total of 167 patients were randomly and
      prospectively assigned to the cilazapril group or the control group. In the
      cilazapril group, 78 patients received a 2 mg dose of cilazparil daily, starting
      7 days before PTCA and continuing for 6 months. Only 128 patients (cilazapril 56,
      control 72) completed the study because 39 dropped out. Coronary angiograms were
      evaluated by the quantitative coronary angiogram (QCA) system. RESULTS: There
      were no differences between the two groups of patients with regard to baseline
      clinical and angiographic characteristics. QCA analysis (cilazapril 66 lesions,
      control 101 lesions): the loss at follow-up in minimal lumen diameter was 0.36 +/
      0.57 mm in the cilazapril group and 0.57 +/- 0.75 mm in the control group (P <
      0.05). Restenosis rate: in the cilazapril group, 16 of 56 patients (28.6%) had
      restenosis in contrast to 36 of 72 patients (50.0%) in the control group (P <
      0.02). When vessel restenosis was evaluated, 16 of 63 vessels (25.4%)
      demonstrated restenosis in the cilazapril group, in contrast to 41 of 82 vessels
      (50.0%) in the control group (P < 0.01). CONCLUSIONS: Treatment using cilazapril
      7 days before PTCA significantly reduced the rate of restenosis. These data
      suggest that previous administration of cilazapril might be important for
      preventing restenosis.

PMID- 7582202
TI  - Spatial statistical methods in environmental epidemiology: a critique.
AB  - Despite recent advances in the available statistical methods for geographical
      analysis, there are many constraints to their application in environmental
      epidemiology. These include problems of data availability and quality, especially
      the lack in most situations of environmental exposure measurements. Methods for
      disease 'cluster' investigation, point source exposures, small-area disease
      mapping and ecological correlation studies are critically reviewed, with the
      emphasis on practical applications and epidemiological interpretation. It is
      shown that, unless dealing with rare diseases, high specificity exposures and
      high relative risks, cluster investigation is unlikely to be fruitful, and is
      often complicated by the post hoc nature of such studies. However, it is
      recognized that in these circumstances proper assessment of the available data is
      often required as part of the public health response. Newly available methods,
      particularly in Bayesian statistics, offer an appropriate framework for
      geographical analysis and disease mapping. Again, it is uncertain whether they
      will give important clues as to aetiology, although they do give valuable
      description. Perhaps the most satisfactory approach is to test a priori
      hypotheses using a geographical database, although problems of interpretation
      remain.

PMID- 7582203
TI  - Spatial heterogeneity, nonlinear dynamics and chaos in infectious diseases.
AB  - There is currently considerable interest in the role of nonlinear phenomena in
      the population dynamics of infectious diseases. Childhood diseases such as
      measles are particularly well documented dynamically, and have recently been the
      subject of analyses (of both models and notification data) to establish whether
      the pattern of epidemics is chaotic. Though the spatial dynamics of measles have
      also been extensively studied, spatial and nonlinear dynamics have only recently
      been brought together. The present review concentrates mainly on describing this
      synthesis. We begin with a general review of the nonlinear dynamics of measles
      models, in a spatially homogeneous environment. Simple compartmental models
      (specifically the SEIR model) can behave chaotically, under the influence of
      strong seasonal 'forcing' of infection rate associated with patterns of
      schooling. However, adding observed heterogeneities such as age structure can
      simplify the deterministic dynamics back to limit cycles. By contrast all current
      strongly seasonally forced stochastic models show large amplitude irregular
      fluctuations, with many more 'fadeouts' of infection that is observed in real
      communities of similar size. This indicates that (social and/or geographical)
      spatial heterogeneity is needed in the models. We review the exploration of this
      problem with nonlinear spatiotemporal models. The few studies to date indicate
      that spatial heterogeneity can help to increase the realism of models. However, a
      review of nonlinear analyses of spatially subdivided measles data show that more
      refinements of the models (particularly in representing the impact of human
      demographic changes on infection dynamics) are required. We conclude with a
      discussion of the implication of these results for the dynamics of infectious
      diseases in general and, in particular, the possibilities of cross fertilization
      between human disease epidemiology and the study of plant and animal diseases.

PMID- 7582204
TI  - Analysing geographically-related disease data.

PMID- 7582208
TI  - Need for emergency treatment in subclavian vein effort thrombosis.
AB  - BACKGROUND: Effort thrombosis of the subclavian vein is often inadequately
      treated--and most of the time treatment is late. Physicians are unfamiliar with
      this syndrome and its treatment. STUDY DESIGN: In 65 patients with this syndrome,
      three major categories were recognized. The acute group (less than one week)
      comprised 14 patients subdivided into first time occurrence, recurrent episode,
      or occurrence after previous surgery for thoracic outlet. The subacute group
      (between one and two weeks) comprised four patients with the same subdivisions as
      the acute group. The chronic group (greater than two weeks) comprised 47
      patients. Acute and subacute cases were treated with direct lytic therapy
      (urokinase) followed by operation. An anterior subclavicular approach was used to
      remove the first rib, subclavius, and anterior scalene muscles and to have safe
      access to the vein. Patients in the chronic stage required vein patch angioplasty
      of the strictured segment. RESULTS: In acute cases (first time occurrence)
      decompression of the vein only at the thoracic outlet was effective in 100
      percent of cases (eight patients). Vein patch angioplasty was needed in
      recurrent, subacute, and chronic cases. This procedure was 100 percent effective
      if stenosis was less than 2 cm long. Longer-segment obstructions had only a 37.5
      percent (three of eight) success rate. Fourteen patients were considered
      inoperable. CONCLUSIONS: It is recommended that effort thrombosis of the
      subclavian vein be treated acutely with thrombolytic agents followed by
      operation. This aims to prevent chronic fibrous obliteration of the subclavian
      vein, which is a consistent complication in patients who have had delayed
      treatment for more than two weeks. If operable, chronic stage patients always
      require vein patch angioplasty.

PMID- 7582205
TI  - Long-term results of operation for carcinoma of the stomach in T1/T2 stages:
      critical evaluation of the concept of early carcinoma of the stomach.
AB  - BACKGROUND: The significance of nodal metastasis in patients with early gastric
      cancer (ECG) (T1) is unknown. It has been suggested that patients with T2, N0
      carcinoma of the stomach have a comparable survival rate to patients with T1
      carcinoma of the stomach. STUDY DESIGN: A retrospective review and survival
      analysis of 321 patients with T1/T2 adenocarcinoma of the stomach treated between
      1979 to 1991 were performed. RESULTS: Patients were divided into four groups:
      group 1, 214 patients with node-negative EGC (T1, N0); group 2, 13 patients with
      node-positive EGC (T1, N+); group 3, 49 patients with node-negative T2 disease
      (T2, N0); and group 4, 45 patients with node-positive T2 disease (T2, N+).
      Excluding deaths from causes other than recurrence, the survival rate for
      patients in groups 1 and 3 was 100 percent, in contrast to the ten-year survival
      rate of 72.7 percent for group 2 and 62.5 percent for group 4 patients (p <
      0.001, groups 1 versus 2, groups 3 versus 4). The ten-year survival rate for
      patients with node-negative T2 disease (group 3, 100 percent) was significantly
      better than that of patients with node-positive EGC (group 2, 72.7 percent) (p <
      0.001). Although differences in the survival rates were noted according to
      lymphatic or venous invasion and whether or not patients had EGC or T2 carcinoma,
      the most significant factor was lymph node invasion. CONCLUSIONS: The
      postoperative survival rate for patients with node-positive EGC was poorer than
      that for those with node-negative T2 carcinomas. Reevaluation of the concept of
      EGC may be necessary. Post-operative chemotherapy does not appear necessary in
      patients with T2, N0 disease.

PMID- 7582206
TI  - The impact of pneumoperitoneum, pneumoretroperitoneum, and gasless laparoscopy on
      the systemic and renal hemodynamics.
AB  - BACKGROUND: The use of therapeutic laparoscopy has become widespread recently. It
      is important to assess the effects of gaseous and gasless laparoscopy on systemic
      and renal hemodynamics. STUDY DESIGN: A prospective controlled animal study was
      performed on 40 well-hydrated pigs. Systemic and renal hemodynamics were
      monitored during peritoneal insufflation, retroperitoneal insufflation, and
      abdominal wall lifting for a period of two hours. A laser Doppler flow meter was
      applied laparoscopically to measure the renal cortical tissue perfusion. RESULTS:
      Peritoneal insufflation of carbon dioxide to a pressure of 15 mm Hg elicited
      transient elevations of the aortic pressure and carotid arterial blood flow.
      Unilateral pneumoretroperitoneum caused a smaller change on systemic
      hemodynamics. Pneumoperitoneum and pneumoretroperitoneum caused oliguria.
      Superficial renal cortical blood flow reduction decreased by an average of 60
      percent in the compressed kidney, and blood flow returned to the pre-insufflation
      level after the pressure was released. A gradual decrease of tissue perfusion in
      the contralateral kidney and a concomitant gradual increase of the intra
      abdominal pressure were observed when pneumo-retroperitoneum was maintained for
      two hours. No significant changes in urinary output and in systemic and renal
      hemodynamics were found when the abdominal wall was lifted up with a force
      equivalent to 15 mm Hg. CONCLUSIONS: Significant systemic and renal hemodynamic
      changes were elicited in gaseous but not in gasless laparoscopy, which may
      explain the decreased urinary output observed during gaseous laparoscopy.
      Pneumoperitoneum caused greater systemic and renal hemodynamic alterations than
      pneumoretroperitoneum; however, the effects were transient and reversible after a
      period of two hours.

PMID- 7582207
TI  - Familial juvenile polyposis: patterns of recurrence and implications for surgical
      management.
AB  - BACKGROUND: Familial juvenile polyposis predisposes to the development of
      carcinoma of the colon. Optimum surgical management and recommended surveillance
      of affected individuals are still being defined. STUDY DESIGN: A retrospective
      review of experience with a kindred identified in 1988 was carried out. RESULTS:
      Of 34 living members, 15 have been investigated, and histologically typical
      juvenile polyps were found in 11. In each instance, polyps were most numerous in
      the right colon, with few polyps in the descending colon and none in the rectum.
      Eight patients have had subtotal colectomies with ileorectal anastomoses; the
      remaining patients were managed by polypectomy (with one recurrence after ten
      years). In addition to juvenile polyps, polyps with adenomatous or villous
      elements were identified in three patients. One of these patients had invasive
      adenocarcinoma in a large mixed polyp of the cecum. Two patients with polyps had
      coexisting carcinoma of the stomach. All patients have been followed up with
      periodic upper and lower gastrointestinal endoscopy. Polyps have recurred in the
      rectal remnants of three patients at a mean of 36 months after subtotal
      colectomy. Two patients have undergone conversion to total proctocolectomy with
      ileoanal anastomosis and J pouch; one patient was found to have juvenile polyps
      in the pouch 40 months after surgery. CONCLUSIONS: Despite the preponderance of
      right-sided polyps at initial diagnosis, the rapid recurrence of polyps after
      subtotal colectomy argues in favor of performing proctocolectomy with
      preservation of anal sphincter function (restorative proctocolectomy) at the time
      of initial surgery. Patients with a small number of polyps may choose instead to
      undergo periodic colonoscopy with colonoscopic polypectomy. An algorithm for
      surveillance and follow-up is proposed.

PMID- 7582209
TI  - Laparoscopy and laparoscopic ultrasonography in staging of carcinoma of the
      esophagus and gastric cardia.
AB  - BACKGROUND: The objective of this prospective study was to assess the
      contribution of laparoscopy combined with laparoscopic ultrasonography (LLU) in
      the preoperative staging of patients with carcinoma of the esophagus and cardia.
      STUDY DESIGN: Preoperative LLU was performed in 56 patients who were selected for
      curative resection of carcinoma of the esophagus (n = 38) or gastric cardia with
      involvement of the distal esophagus (n = 18) after routine preoperative workup.
      During LLU, the peritoneal cavity was scrutinized for metastatic disease, and
      ultrasonography of the liver and celiac axis was performed. In all patients
      without histologically proven metastases, laparotomy was then performed. RESULTS:
      The morbidity rate of the procedure was 3.5 percent (two superficial wound
      infections). In three (5 percent) of the 56 patients, laparotomy was excluded by
      the presence of intra-abdominal metastases. In three other patients, laparotomy
      was necessary to confirm the suspected hepatic or peritoneal metastases, or both,
      because histologic proof was not obtained at laparoscopy. In one patient, LLU
      failed to detect a small hepatic metastasis in segment VII. The preoperative
      stage was altered by laparoscopy in nine (17 percent) patients (M1 in six, T4 in
      three). Laparotomy was avoided in two (11 percent) and the preoperative stage
      changed in seven patients (41 percent), all of whom had carcinoma of the gastric
      cardia, as occurred in one (3 percent) and two (6 percent) patients with middle
      and distal carcinoma of the esophagus, respectively. CONCLUSIONS: Preoperative
      staging by LLU is of little value in patients with carcinoma of the middle and
      lower esophagus. The probable role of LLU in the staging of patients with
      carcinomas of the gastric cardia remains to be confirmed in larger series.

PMID- 7582210
TI  - Congenital stenosis of the intrahepatic bile duct associated with choledochal
      cysts.
AB  - BACKGROUND: There are few studies that report on stenosis of the intrahepatic
      bile ducts associated with choledochal cysts. We investigated the presence and
      clinical significance of stenosis of the intrahepatic bile ducts associated with
      choledochal cysts. STUDY DESIGN: We examined intrahepatic bile ducts in patients
      with choledochal cysts using cholangiography (93 patients), endoscopy and direct
      observation during surgery (19 patients), and histologic examination (12
      patients). RESULTS: Stenosis of the intrahepatic bile duct was present in 75
      (80.6 percent) of 93 patients with choledochal cysts. Endoscopic and direct
      observation detected membranous stenosis, which consisted of a diaphragm, in 11
      of 19 patients. Septal stenosis, which consisted of a bridge-like septum, was
      present in eight of 19 patients. Stenoses consisted of mucosal and fibromuscular
      layers. Intrahepatic calculi developed in eight patients with stenosis following
      resection of the choledochal cysts. CONCLUSIONS: Membranous or septal stenosis of
      the intrahepatic bile duct is a characteristic feature of choledochal cysts. Our
      findings suggest that these stenoses should be treated surgically because of the
      risk of intrahepatic calculi.

PMID- 7582212
TI  - Mechanisms of adaptation to hypoxia in energy metabolism in rats.
AB  - BACKGROUND: Oxygen supply to the tissues is needed in the early postoperative
      period to meet the energy requirements for maintaining cellular activity. This
      study was done to investigate energy metabolism in rats during hypoxia in order
      to determine the mechanism underlying the acclimatization of energy production to
      oxygen depletion. STUDY DESIGN: Wistar rats were divided into two experimental
      groups: hypoxic and normoxic, which were supplied with 10 and 21 percent oxygen
      for 20 hours, respectively. At the end of the experiment, blood and hepatic
      tissue samples were taken to determine endocrine and metabolic responses to
      hypoxia. Energy expenditure during hypoxia was also evaluated. RESULTS: Hypoxia
      resulted in marked increases in blood concentrations of triglycerides, free fatty
      acids, catecholamines, and corticosterone. Hypoxia marked by depressed resting
      energy expenditure and respiratory quotient, and produced a stable hepatic
      adenosine triphosphate (ATP) level. The cytosolic redox state, represented by the
      ratio of lactate to pyruvate concentrations in the liver, and the arterial ketone
      body ratio declined during hypoxia. With hypoxia, an increase in alanine and
      decreases in glutamine and glutamate levels in the liver were observed.
      CONCLUSIONS: These results suggest that hypoxia depresses energy expenditure,
      which leads to a normoxic level of hepatic ATP. Fat is a main metabolic fuel
      during hypoxia. Hypoxia leads to the development of a pathway that shunts
      pyruvate and glutamate to alanine and alpha-ketoglutarate, allowing efficient
      energy production.

PMID- 7582211
TI  - Failure of intestinal amino acid absorptive mechanisms in sepsis.
AB  - BACKGROUND: Sepsis has been shown to impair the barrier function and metabolism
      of the intestine. This study was done to investigate the effect of sepsis on
      intestinal absorption of proline, leucine, glutamic acid, and aminoisobutyric
      acid. STUDY DESIGN: Rats (six per group) were studied 24 hours after cecal
      ligation and puncture (CLP) or six hours after intraperitoneal injection of
      lipopolysaccharide (LPS). Controls underwent sham laparotomy or saline solution
      injection. Four 7-cm everted proximal jejunal sacs were prepared from each rat
      and filled with 800 microL Krebs' bicarbonate buffer containing 100 mumol/L of
      amino acid. Paired sacs (septic and control) were incubated at 37 degrees C in
      flasks containing the same solution trace labeled with 3H containing the same
      solution trace labeled with 3H amino acid. Sac contents were aspirated 60 minutes
      later and amino acid uptake was determined by scintillation counting. RESULTS:
      Twenty-four hours after CLP and six hours after LPS administration there was
      significant impairment in the intestinal absorption of all amino acids studied.
      Absorption of glutamic acid was the least affected, followed by leucine,
      aminoisobutyric acid, and proline. CONCLUSIONS: Sepsis impairs the intestinal
      absorption of amino acids. The magnitude of this defect in absorption differed
      with the amino acid studied, suggesting that not all transport systems were
      affected equally. This differential response of transport systems to sepsis
      appears to be the inverse of what is observed after a period of starvation.

PMID- 7582213
TI  - Functional results of the double-stapled ileoanal reservoir.
AB  - BACKGROUND: The preferred method for creation of an ileoanal reservoir is still
      controversial. We prospectively studied the functional and physiologic outcome of
      our patients who underwent a double-stapled ileoanal reservoir (DSIAR). STUDY
      DESIGN: All consecutive patients who underwent restorative proctocolectomy with a
      DSIAR between 1988 and 1993 were evaluated. Functional results were assessed by
      questionnaires and anal manometry preoperatively and two, 12, and 24 months
      postoperatively. RESULTS: One hundred forty patients (90 males and 50 females)
      with a mean age of 40.7 (range, 12 to 71) years were evaluated. Of these, 107
      patients (77 percent) had ulcerative colitis, 21 (15 percent) had familial
      adenomatous polyposis, six (4 percent) had indeterminate colitis, and six (4
      percent) had a post-operative diagnosis of Crohn's disease. One hundred twenty
      four (95 percent) of the 131 patients with closed stomas were available for
      functional and manometric evaluation at a mean follow-up period of 24 months. A
      32 percent decline in the mean resting pressure (from 71.3 +/- 4 to 48.2 +/- 3.4
      mm Hg) occurred early after DSIAR (p < 0.001) with partial recovery by 24 months.
      The maximal internal sphincter resting pressure showed a 39 percent decline (from
      90.8 +/- 4.9 to 55.3 +/- 5.7 mm Hg, p < 0.005) with recovery after 12 months.
      There were no significant changes in the length of the high-pressure zone or mean
      or maximal squeeze pressures. A mean of 5.4 (two to 13) bowel movements occurred
      during the day and a mean of 1.2 (zero to four) occurred at night. Perfect or
      almost perfect continence was reported during the day and night, respectively, by
      95 and 92 percent of the patients. Overall perioperative complications occurred
      in 30 patients (21 percent) including septic complications in eight (6 percent),
      and pouchitis in eight (6 percent). There was one postoperative death (0.7
      percent). CONCLUSIONS: Double-stapled ileoanal reservoir is associated with good
      subjective functional and objective physiologic results and has acceptable rates
      of morbidity and mortality.

PMID- 7582214
TI  - Role of dipyridamole myocardial scintigraphy in carotid artery surgery.
AB  - BACKGROUND: Absence of cardiac symptoms is not a valid indicator of low cardiac
      risk in the sedentary patient who is being considered for vascular surgery.
      Invasive methods of cardiac assessment in such patients are associated with risk
      and are expensive. This study was carried out to evaluate the utility of pre
      operative cardiac risk stratification with dipyridamole myocardial scintigraphy
      (DMS), in patients to undergo carotid artery surgery. STUDY DESIGN: From 1991 to
      1994, 174 of 266 carotid endarterectomy patients underwent preoperative DMS. The
      ability of clinical factors and DMS to predict postoperative cardiac morbidity
      was assessed retrospectively in a nonrandomized fashion. RESULTS: Forty-seven
      adverse cardiac events (deaths = 0, myocardial infarction (MI) = 4, congestive
      heart failure (CHF) = 9, angina = 7, and new dysrhythmias = 27) occurred in 38
      (14.3 percent) of 266 patients. Results of DMS were 73 percent normal, 10.3
      percent fixed defect, and 16.7 percent reversible defect examinations.
      Sensitivity and specificity of DMS was 32 and 74 percent for total cardiac
      morbidity, and 50 and 74 percent for MI. The positive predictive value of DMS for
      MI, dysrhythmias, CHF, angina, and all cardiac events was 4, 11, 9, zero, and 23
      percent, respectively. Negative predictive values were 98, 91, 98, 95, and 82
      percent, respectively. Preoperative histories of MI and chest pain were
      significant independent predictors of adverse cardiac outcomes (p < 0.05) while
      age greater than 70 years, smoking, hypertension, diabetes mellitus, preoperative
      arrhythmias, and DMS were not. CONCLUSIONS: Dipyridamole myocardial scintigraphy
      is an ineffective predictor of adverse cardiac events in patients being evaluated
      for carotid artery surgery and its routine use is not justified.

PMID- 7582216
TI  - The forgotten first career of Doctor Henry Van Dyke Carter.
AB  - BACKGROUND: While Henry Gray's Anatomy: Descriptive and Surgical, first published
      in 1858, is distinguished by superb illustrations, its original illustrator is
      remembered for an entirely different set of accomplishments, notably significant
      contributions to tropical medicine. STUDY DESIGN: Literature review. RESULTS: Dr.
      Henry Van Dyke Carter, Professor of Anatomy and Physiology and subsequently Dean
      of the Grant Medical College in Bombay, India, was a skillful researcher and keen
      clinician who made significant contributions to tropical medicine, including the
      discovery of Spirillum minus, the spirochetal organism that causes relapsing
      fever. For his discoveries he was honored by both the British Medical Association
      and the English government. Before his departure for India in 1858, however, he
      and Henry Gray worked at St. George's Hospital Medical School and collaborated on
      the first edition of the text that is still the "Bible" of anatomy to many
      medical students. His drawings have appeared in every subsequent edition, up to
      the present day. CONCLUSIONS: During his first career as a medical illustrator,
      Carter was responsible for the drawings that have helped generations of
      physicians to master the intricacies of human anatomy.

PMID- 7582215
TI  - Cardiac tamponade caused by central venous catheter perforation of the heart: a
      preventable complication.
AB  - BACKGROUND: Pericardial tamponade caused by central venous catheter perforation
      of the heart is a catastrophic complication that can be prevented by attention to
      proper positioning of the catheter tip proximal to the cardiac silhouette. This
      study was performed to determine awareness of this potential complication among
      physicians and to suggest measures to minimize the incidence of this problem.
      STUDY DESIGN: Clinical and radiologic features of 11 cases were evaluated. House
      officers and attending staff who frequently pass central venous catheters and
      train junior physicians to place these catheters were questioned specifically to
      test their awareness of this complication and their knowledge of optimal catheter
      tip positioning. Attending radiology staff physicians were questioned similarly.
      The written protocols of local community hospitals with respect to central venous
      catheter placement were reviewed to determine their criteria for optimal catheter
      placement. RESULTS: Ten of the 11 cases reviewed resulted in death; the 11th case
      resulted in severe anoxic brain insult with a persistent vegetative state. In the
      ten cases that had radiologic studies available for review, the central venous
      catheter tip was seen to lie malpositioned within the cardiac silhouette.
      Questioning of house officers and attending staff as well as attending radiology
      staff revealed a lack of awareness of this problem generally and a lack of
      knowledge of optimal catheter tip positioning specifically. The protocols of area
      hospitals revealed similar findings with respect to this potential complication.
      CONCLUSIONS: Pericardial tamponade resulting from central venous catheter
      perforation of the heart can be avoided by adherence to proper technique in the
      placement of these catheters, ensuring that the catheter tip lies proximal to the
      cardiac silhouette, optimally in the superior vena cava, 2 cm proximal to the
      pericardial reflection. Physicians who place these catheters and train others to
      do so must be aware of this issue and they must educate their trainees as well.
      Radiologists responsible for interpreting the roentgenographs of the chest
      obtained after catheter placement should be alert to catheter malposition and
      communicate this information promptly. Hospital protocols should deal with this
      issue explicitly and insist on repositioning of catheters if catheter tips are
      seen to lodge in suboptimal positions.

PMID- 7582218
TI  - Laparoscopic pneumoperitoneum: the abdominal compartment syndrome revisited.

PMID- 7582217
TI  - Lymph node involvement in T1/T2 carcinoma of the stomach.

PMID- 7582219
TI  - Chopstick retention suture for the closure of abdominal wounds.

PMID- 7582220
TI  - Technique for subpectoral implantation of cardioverter defibrillators.

PMID- 7582221
TI  - Prone scintimammography in patients with suspicion of carcinoma of the breast.

PMID- 7582222
TI  - Carcinoma of the pancreas: critical analysis of costs, results of resections, and
      the need for standardized reporting.
AB  - BACKGROUND: The incidence of carcinoma of the pancreas is increasing in Western
      societies at great cost. Pancreatic resections have been performed for 60 years
      and there are hundreds of papers written on the subject, but there is no
      agreement on the efficacy of resections. Authors have reported on different
      groups and subsets of patients and have used different statistical methods. Most
      authors are unable to report a single five-year survivor; others claim a five
      year survival rate of 30 to 55 percent. STUDY DESIGN: I have standardized and
      compared the results reported in 340 papers that deal with survival rates and
      where there is apparently adequate confirmation of disease. RESULTS: Survivors
      who have been resected may be reported up to six times even from different
      countries, whereas survivors who were not resected are frequently overlooked.
      Actuarial statistical methods exaggerate results when data are lost. After
      corrections for repetitions, approximately 300 survivors were found, of whom 10
      percent had not undergone resection, of the estimated 80,000 patients reported.
      The overall survival rate was less than 0.4 percent. The best overall survival
      rate in surgical studies reported in detail is only 3.6 percent and for a
      nonsurgical study it was 1.7 percent. The average excess cost for each resection
      was at least $150,000. With only one in 30 patients who underwent resection
      living for five years, the cumulative cost per "successful" resection was
      therefore approximately $4.5 million. CONCLUSIONS: Pancreatic resections have had
      minimal impact on survival rates in patients with carcinoma and are wasteful of
      resources.

PMID- 7582223
TI  - Laparoscopic cholecystectomy can disseminate in situ carcinoma of the
      gallbladder.
AB  - BACKGROUND: Early case reports suggest more frequent and rapid recurrences of
      carcinoma of the gallbladder after laparoscopic cholecystectomy (LC) than after
      open cholecystectomy. This cancer has a poor prognosis and occurs in 1 percent of
      patients who undergo cholecystectomies. STUDY DESIGN: A recent community hospital
      series of gallbladder carcinoma (GBC) was reviewed and the total reported
      experience of GBC after LC was compiled. Diagnostic findings were compared for
      patients with GBC and a consecutive series of 24 patients who had LC for benign
      disease. RESULTS: Nine patients with GBC were found among 928 patients who had
      undergone cholecystectomy (0.97 percent incidence). Compared to patients without
      GBC, patients with carcinoma were older, had thicker gallbladder walls, and had
      more abnormalities detected intraoperatively (all p < or = 0.05). Recurrence of
      GBC occurred more rapidly after LC, and in diffuse peritoneal and port sites when
      compared with recurrence patterns after open cholecystectomy. CONCLUSIONS: In
      patients with GBC, LC may be sufficient when the disease is confined to the
      gallbladder mucosa and the gallbladder is excised intact without bile spillage.
      However, patients whose gallbladders are torn during dissection or patients who
      have invasive tumors should undergo laparotomy and local reexcision. In situ GBC
      can be implanted if the organ is torn during dissection. When gallbladders with
      suspicious wall thickening or adhesions are noted at LC, especially in older
      patients, the procedure should be converted to open cholecystectomy.

PMID- 7582225
TI  - Infectious morbidity, operative blood loss, and length of the operative procedure
      after cesarean delivery by method of placental removal and site of uterine
      repair.
AB  - OBJECTIVE: This study was done to determine the impact of the method of placental
      removal and the site of uterine repair on postcesarean infectious morbidity rates
      in women receiving prophylactic antibiotics at cesarean delivery. STUDY DESIGN:
      This prospective study included 284 women who underwent cesarean delivery and who
      were randomly assigned to four groups based on the method of placental removal
      and the site of uterine repair: group 1, spontaneous placental removal and in
      situ uterine repair; group 2, spontaneous placental removal and exteriorized
      uterine repair; group 3, manual placental removal and in situ uterine repair; and
      group 4, manual placental removal with exteriorized uterine repair. Exclusion
      criteria were repeat cesarean deliveries without labor, active infection at the
      time of cesarean delivery, and patient refusal to participate. RESULTS: There was
      no significant difference among the groups in maternal age, race, parity, weight,
      the length of time from rupture of membranes (ROM) or the number of vaginal
      examinations from ROM to cesarean delivery, or preoperative hematocrit.
      Intraoperatively, the type of uterine incision, anesthesia administered,
      incidence of meconium-stained amniotic fluid, Apgar scores, and cord gases were
      similar between groups. The incidence of postcesarean endometritis was greater in
      group 4 (32 [45 percent] of 71, p = 0.003) compared with group 1 (17 [24 percent]
      of 71), group 2 (12 [30 percent] of 71); and group 3 (13 [18 percent] of 71).
      CONCLUSIONS: Manual placental removal and exteriorization of the uterus for
      repair of the surgical incision increases the infectious morbidity rate in women
      receiving prophylactic antibiotics at the time of cesarean delivery and increases
      the length of hospitalization.

PMID- 7582224
TI  - Alternative methods for below-knee amputation: reappraisal of the Kendrick
      procedure.
AB  - BACKGROUND: In 1956, Kendrick described a technique for below-knee amputation
      (BKA) using anterior and posterior flaps in a length ratio of 1:2. There has been
      no review of the utility and safety of this technique over the past four decades.
      STUDY DESIGN: The Kendrick method was studied in 96 consecutive patients who
      underwent 100 BKAs from 1982 to 1995. Follow-up examination was continued through
      the period of rehabilitation and included all revisional surgery. RESULTS: Eighty
      one patients had diabetes mellitus, 15 patients were nondiabetic, and the mean
      age was 67 years (range, 12 to 94 years). Fifty-seven patients underwent BKA for
      diabetic foot sepsis with healing failure after debridement or nonreconstructable
      vascular disease, 19 patients underwent BKAs for progressive necrosis despite a
      patent arterial reconstruction, and 24 patients underwent BKAs for other causes,
      including microembolism, calciphylaxis-related gangrene, bypass failure, trauma,
      frostbite, and calf-wound healing failure after coronary revascularization.
      Preliminary guillotine amputations were performed on three limbs. There was an
      incision in the calf from previous vascular surgery in 25 limbs. The 30-day
      mortality rate was 6 percent. Healing of the stump and knee salvage occurred in
      93 limbs (93 percent). Four patients had local wound complications develop in the
      stump, yet they eventually healed. During the follow-up period, conversion to an
      above-knee amputation was necessary in seven patients, five within 30 days. Only
      one of these was in a limb with a previous arterial reconstruction in the calf.
      CONCLUSIONS: The Kendrick procedure for BKA with anterior and posterior flaps is
      efficacious and safe. This procedure is advantageous for its anatomic basis, the
      ease with which the flaps can be designed despite leg edema or overall size, and
      the ability of the surgeon to distance the posterior flap margin from sepsis in
      the lower one-third of the calf.

PMID- 7582226
TI  - Determinants of success with spot localization biopsy of the breast.
AB  - BACKGROUND: The accurate diagnosis of nonpalpable lesions of the breast by spot
      localization biopsy depends upon numerous variables. STUDY DESIGN: Multivariate
      analysis was used to identify variables influencing the success of spot
      localization biopsy of 757 lesions (27.3 percent of which were malignant) in 738
      patients. RESULTS: Ninety percent of the lesions were removed with the first
      excision as documented by specimen radiography, but 2.3 percent (18 lesions) were
      not evident on specimen radiography with up to four excisional attempts. Eight
      (44 percent) of these 18 were in fact removed because they could not be seen on
      follow-up mammograms. Lesions with calcifications only were significantly more
      difficult to remove than were masses (87 compared with 96 percent, respectively,
      p < 0.001). The use of both hooked wire and methylene blue dye was significantly
      less successful than wire or dye alone (84 compared with 93 and 91 percent,
      respectively, p < 0.001). A second attempt was successful in 71 percent (52
      lesions) of the remaining 75 percent lesions and additional attempts at excision
      were often associated with success. Success was highly variable among surgeons
      but could not be related to experience. CONCLUSIONS: Calcifications are more
      difficult to remove than masses, and combining hooked wire with dye does not
      improve the success rate. Additional excisional attempts are worthwhile if the
      lesion is not seen on the first radiograph of the specimen.

PMID- 7582227
TI  - Bile acids and microorganisms in the jejunal lumen after biliary reconstruction
      in dogs.
AB  - BACKGROUND: This study evaluated the composition of various bile acids and
      microorganisms in the jejunal lumen after using different methods of biliary
      reconstruction. STUDY DESIGN: A Billroth I biliary reconstruction, in which the
      biliary tract was directly anastomosed to the alimentary tract, was performed in
      16 dogs, including eight with cholecystoduodenostomy (C-D group) and eight with
      cholecystojejunostomy (C-J group). A Billroth II reconstruction, involving a
      Rouxen-Y cholecystojejunostomy (R-Y group) in which bile flowed into the jejunal
      limb, was made in eight dogs. Jejunal fluid samples were used for microbial
      culture and bile acid assay by high-performance liquid chromatography. RESULTS:
      The percentage of unconjugated bile acids in the R-Y group (9.96 +/- 2.17
      percent) was significantly higher than that observed in the C-D group (0.11 +/-
      0.05 percent), and that observed in the C-J group (1.05 +/- 0.72 percent) (p <
      0.01). The detection rate of anaerobes was higher in the R-Y group than in the C
      D and C-J groups. CONCLUSIONS: This study suggests that due to an increase in
      unconjugated bile acids after the Billroth II biliary reconstruction the function
      of digestion and absorption is less well preserved than after the Billroth I
      method.

PMID- 7582228
TI  - Abdominal computed tomographic scan in the selection of patients with mucinous
      peritoneal carcinomatosis for cytoreductive surgery.
AB  - BACKGROUND: Cytoreductive surgery and intraperitoneal chemotherapy have been used
      to treat peritoneal carcinomatosis. A complete surgical resection is required for
      optimal results to be achieved. This study evaluated the preoperative computed
      tomographic (CT) findings in patients with mucinous peritoneal carcinomatosis in
      order to predict the probability of a complete resection. STUDY DESIGN: Computed
      tomographic scans of the abdomen and pelvis were reviewed retrospectively in 45
      patients with a diagnosis of mucinous peritoneal carcinomatosis who were treated
      with surgery and intraperitoneal chemotherapy. According to the completeness of
      cytoreduction, patients were divided into two groups. Patients in the first group
      (n = 25) had complete cytoreduction (CR) with no tumor deposits 2.5 mm in
      diameter or larger left behind. The surgical resection of tumor was incomplete in
      the second group of patients (n = 20). Sixteen CT parameters were initially
      examined in each group of patients and statistically evaluated according to the
      completeness of the cytoreductive surgical procedure. RESULTS: The incidences of
      six CT findings were significantly different in the two groups of patients. These
      findings were: tumor volume in small bowel mesentery (p < 0.001), tumor volume in
      proximal jejunum (p = 0.003), tumor volume in distal jejunum (p = 0.002), tumor
      volume in proximal ileum (p = 0.003), mesentery configuration (p < 0.001), and
      obstruction of bowel segments by tumor (p < 0.001). A statistical approach using
      a tree-structured diagram showed that patients with both obstruction of bowel
      segments by tumor and tumor diameter greater than 0.5 cm on small bowel surfaces
      exclusive of distal ileum on preoperative CT scan, had an 88 percent probability
      of incomplete resection. Patients without these two CT findings had a 92 percent
      probability of complete resection. CONCLUSIONS: This study shows that selection
      criteria for patients with mucinous peritoneal carcinomatosis are available on a
      preoperative CT scan of the abdomen and pelvis. Patients whose scans show
      obstruction of bowel segments by tumor and tumor diameter greater than 0.5 cm on
      small bowel surfaces exclusive of distal ileum are unlikely to be candidates for
      cytoreductive surgery for the treatment of peritoneal carcinomatosis.

PMID- 7582229
TI  - Application of American College of Surgeons' field triage guidelines by pre
      hospital personnel.
AB  - BACKGROUND: The American College of Surgeons' Committee on Trauma (ACSCOT) has
      developed field triage guidelines intended to identify seriously injured
      patients. Unlike the 1990 version, the 1993 revision calls for on-line medical
      control assistance with the triage decision for patients whose only marker of
      severe injury is the mechanism of their injury. We prospectively examined the
      application of the 1990 ACSCOT field triage guidelines to evaluate Emergency
      Medical Service (EMS) utilization of these guidelines and the potential effects
      of the 1993 revision. STUDY DESIGN: Emergency Medical Service personnel
      identified all ACSCOT criteria applicable to patients delivered to the level 1
      trauma center at the Medical University of South Carolina. Trauma registry data
      were used to compare actual injury severity with applicable indicators. Patients
      with an injury severity score greater than or equal to 16 were considered
      seriously injured. The South Carolina state trauma and EMS databases were queried
      to estimate systemwide overtriage and undertriage rates. RESULTS: Questionnaires
      were completed for 753 patients over 19 months of study. One hundred twenty-two
      patients had serious injuries. The estimated systemwide overtriage and
      undertriage rates were 2.7 and 20.3 percent, respectively. Physiologic criteria
      had a 64.8 percent sensitivity and a 41.8 percent positive predictive value
      (PPV). The addition of anatomic criteria increased sensitivity to 82.8 percent
      and decreased PPV to 26.9 percent. Adding mechanism of injury increased
      sensitivity to 95.1 percent but further reduced PPV to 18.2 percent. Review of
      EMS records suggests that the addition of on-line medical control for patients in
      whom only the mechanism of injury triage guidelines apply could improve PPV with
      little effect on sensitivity. CONCLUSIONS: The current ACSCOT field triage
      guidelines are appropriate when applied by field EMS personnel.

PMID- 7582230
TI  - Gastrointestinal motor activity after pylorus-preserving gastrectomy with or
      without vagotomy in dogs.
AB  - BACKGROUND: In the present study we evaluated gastrointestinal motility after
      gastrectomy of a new pylorus-preserving technique that is becoming a popular
      operation for early stage carcinoma of the stomach. STUDY DESIGN: Using strain
      gauge force transducers we studied gastrointestinal motility in control dogs,
      dogs after pylorus-preserving gastrectomy, and dogs after conventional distal
      gastrectomy with Billroth I reconstruction. Dogs with gastrectomy were reoperated
      upon after recording motility patterns, and the effect of vagal denervation of
      the gastric remnant on motility was investigated. Overall motility pattern,
      length of the digestive phase in the jejunum, and interval of the interdigestive
      phase III contractions were studied and compared among the three groups. RESULTS:
      In dogs after gastrectomy without vagal denervation, the regular occurrence of
      interdigestive phase III contractions from the gastric remnant to the jejunum was
      identified. In dogs after gastrectomy with vagal denervation, however, no
      apparent interdigestive phase III contractions were observed in the gastric
      remnant. The duration of the digestive phase in the jejunum, which correlates
      with postprandial gastric emptying, was not different between the control dogs
      and the dogs having pylorus-preserving gastrectomy. However, this duration was
      significantly shorter in dogs having conventional distal gastrectomy compared
      with the control dogs, not only before but after vagal denervation. CONCLUSIONS:
      These results indicate that the postoperative motor function after pylorus
      preserving gastrectomy may be superior to that after conventional distal
      gastrectomy with Billroth I reconstruction.

PMID- 7582231
TI  - Complete robot-assisted laparoscopic urologic surgery: a preliminary report.
AB  - BACKGROUND: The feasibility and applicability of using surgeon-controlled robotic
      arms as a substitute for surgical assistants during urologic laparoscopic surgery
      was assessed. STUDY DESIGN: Seventeen laparoscopic procedures (nephrectomy, n =
      4; retroperitoneal lymph node sampling, n = 2; varix ligation, n = 2;
      pyeloplasty, n = 3; Burch bladder suspension, n = 2; pelvic lymph node
      dissection, n = 1; orchiopexy, n = 1; ureterolysis, n = 1; and nephropexy, n = 1)
      were performed by a single laparoscopic surgeon assisted by one or two robotic
      arms directly controlled by the operating surgeon. One robotic arm controlled the
      laparoscope and was maneuvered by a foot pedal. The second robotic arm served as
      a retractor and was manipulated by a hand control. Assessment of robotic
      positioning, laparoscopic instrument port placement, time for setup and breakdown
      of the operative field, operative time, outcome, and operative complications were
      made for each procedure and compared with historical human-assisted laparoscopic
      procedures. RESULTS: Standard laparoscopic port placement was adequate for use of
      the robotic arms. All procedures were successfully completed with three minor
      surgical complications not related to the use of the robotic arm. Robotic arm
      positioning on the operating room table differed for each type of procedure, yet
      placement of the robotic arm controlling the laparoscope on the surgeon's side
      provided optimal surgical views. In three cases, intraoperative bleeding required
      human assistance for camera control. There was no increase in operating time when
      the robotic arms were used. There was no difference between the setup and
      breakdown time for this series of complete robot-assisted procedures when
      compared with either a nonrobot-assisted series (p > 0.05) or another robotic
      series completed prior to initiation of this study when no focus was made on
      setup and breakdown times and in which the robotic arm and human surgical
      assistant were compared (p < 0.05). CONCLUSIONS: We found that simultaneous use
      of remote controlled robotic arms as surgical assistants is feasible in
      genitourinary laparoscopic surgery. The potential long-term cost effectiveness of
      using robotic surgical assistants in laparoscopic surgery highlights the economic
      impact of this research and warrants further investigation.

PMID- 7582232
TI  - Management of patients with carcinoma of the pancreas.

PMID- 7582234
TI  - Locking a continuous running suture.

PMID- 7582233
TI  - Unexpected complication of laparoscopic cholecystectomy.

PMID- 7582235
TI  - A simple technique for the closure of laparoscopic trocar wounds.

PMID- 7582236
TI  - Inflammatory and immunologic effects of obstructive jaundice: pathogenesis and
      treatment.

PMID- 7582237
TI  - Elective lymph node dissection.

PMID- 7582238
TI  - Endothelin-1 and prostaglandin E2 levels increase in patients with burns.

PMID- 7582239
TI  - Genetic alterations associated with the evolution and progression of astrocytic
      brain tumours.
AB  - Diffusely infiltrating low-grade astrocytomas (WHO grade II) have an intrinsic
      tendency for progression to anaplastic astrocytoma (WHO grade III) and
      glioblastoma (WHO grade IV). This change is due to the sequential acquisition of
      genetic alterations, several of which have recently been identified. In low-grade
      astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome
      17p are the principal detectable change. Anaplastic astrocytomas contain p53
      mutations at an overall incidence of 34% and, in addition, loss of heterozygosity
      on chromosome 19q and frequent homozygous deletion of the p16 tumor suppressor
      (MTS-1) gene. The most malignant astrocytic neoplasms, the glioblastoma, further
      shows loss of chromosome 10 and amplification of the epidermal growth factor
      receptor (EGF-R) gene at overall incidences of 66% and 34%, respectively. The
      type and distribution of p53 mutations in astrocytic brain tumours are not
      suggestive of specific environmental carcinogens operative in their aetiology.
      Analysis of 91 families with p53 germline mutations reported to date show that
      tumours of the nervous system account to 12% of all neoplasms. Of a total of 57
      brain tumours reported, 30 were classified histologically and of these, 73% were
      of astrocytic origin. The observation that somatic p53 mutations in sporadic
      brain tumours are largely restricted to those of astrocytic origin and that
      astrocytomas also prevail among CNS neoplasms associated with p53 germline
      mutation strongly suggests, that p53 mutations are capable of initiating
      neoplastic transformation in astrocytes of the human nervous system.

PMID- 7582240
TI  - Gastric adenoma-carcinoma sequence with special reference to p53 and Ki-ras gene
      alterations.
AB  - With the aim of detecting the timing of p53 and Ki-ras gene alterations in the
      gastric adenoma-carcinoma sequence, 19 early gastric adenocarcinomas arising from
      adenomas were studied. Immunohistochemically, 5 adenocarcinomas were positive for
      p53; 3 focally and 2 diffusely. The p53 point mutations were detected in a focal
      area with p53 immunoreactivity in 2 of the 5 p53-positive adenocarcinomas. This
      indicated that p53 point mutations may play a less crucial part in malignant
      conversion of adenoma to adenocarcinoma in the stomach than in the colon. No Ki
      ras gene mutations at codons 12 and 13 were detected in any lesion. These results
      suggest that the adenoma-carcinoma sequence in the stomach has a different
      mechanism from that in the colon.

PMID- 7582242
TI  - Declining density of intimal smooth muscle cells and age as preconditions for
      atheronecrosis in the basilar artery.
AB  - The aging basilar artery has some differences and some similarities when compared
      with the aorta and coronary arteries. As the non-necrotic intimal thickness
      increases over time, the number of smooth muscle cells reaches a steady state
      around age 25-30 years in the coronaries and aorta, but continues to increase in
      the basilar artery, even to 90 years of age. The numbers of cells per unit of
      tissue (the cell density) declines with age, and the patterns of decline are
      quantitatively similar in all three arterial segments. All arteries so far
      examined behave alike in showing that atheronecrosis emerges in those specimens
      that have sufficiently low density of intimal smooth muscle cells. These results
      identify low intimal cell density as a criterion for recognizing arteries that
      are prone to atheronecrosis. One possible explanation is that depopulation of the
      fibrotically thickened and aged intima, by spreading apart the smooth muscle
      cells with expanding matrix materials, could be the conditioning factor that
      brings about the intrusion of atheronecrosis.

PMID- 7582241
TI  - Expression of GM-CSF receptor by Langerhans' cell histiocytosis cells.
AB  - Langerhans' cell histiocytosis (LCH) is characterized by the proliferation of
      large mononucleated cells containing Birbeck granules and expressing CD1a. Recent
      studies have demonstrated that LCH is a clonal proliferation; however, its
      aetiology is still unknown. Growth and differentiation of bone-marrow-derived
      cells are controlled by cytokines. The proliferation, differentiation and
      activation of normal Langerhans cells are controlled by granulocyte/macrophage
      colony-stimulating factor (GM-CSF) in vitro. Therefore, GM-CSF could be
      implicated in the pathogenesis of LCH. Indeed, LCH cells contain GM-CSF, and
      children with disseminated LCH have an elevated GM-CSF serum level. As a cytokine
      only acts on cells expressing a specific receptor, we investigated the presence
      of GM-CSF receptor on LCH cells. Fourteen frozen tissue samples from children
      with LCH were studied by in situ immunohistochemistry with two mouse monoclonal
      antibodies specific for the alpha chain of the GM-CSF receptor (CDw116). LCH
      cells of all the samples were positively stained with both antibodies. This study
      suggests that GM-CSF may be a growth factor for LCH cells.

PMID- 7582243
TI  - Atypical mitotic figures and the mitotic index in cervical intraepithelial
      neoplasia.
AB  - We surveyed cervical intraepithelial neoplasia (CIN) to quantify the
      proliferation rate and the presence of normal and atypical mitotic figures. In
      the cervical tissue specimens of 127 women with CIN, the area with the highest
      cell proliferation was identified and, at that site, the proliferation rate was
      assessed by calculating the mitotic index (MI). Lesions with an MI < 2 were not
      considered further. In the area with the highest proliferation rate, 228 mitoses
      were classified into one of the following groups: normal mitotic figures (NMFs),
      lag-type mitoses (OLTMs) comprising three group metaphases (3GMs), two group
      metaphases (2GMs) and other lag-type mitoses (LTMs), multipolar mitoses (MPMs)
      comprising tripolar mitoses (3PMs) and quadripolar mitoses (4PMs), and other
      atypical mitotic figures (OAMFs). The median value of the MI increased
      significantly from 3 in CIN I through 4 in CIN II to 9 in CIN III (P < 0.001).
      The occurrence of the different LTMs was mutually correlated. The frequency of
      LTMs increased significantly with increasing CIN grade (P < 0.001), whereas the
      frequency of NMFs decreased significantly with increasing CIN grade (P < 0.001).
      The frequency of OAMFs was not related to CIN grade (P = 0.94). MPMs were present
      in low numbers in a minority of the lesions. Spearman's rank correlation
      coefficient (with 95% confidence limits) between the MI and the number of LTMs,
      OAMFs and NMFs was 0.66 (0.53; 0.75), -0.14 (-0.32; 0.05) and -0.51 (-0.63; 
      0.35), respectively. Increasing CIN grade is associated with increasing MI,
      increasing numbers of LTMs, and decreasing numbers of NMFs. MPMs are very rare
      events in CIN. The abundant presence of OAMFs seems to be independent of CIN
      grade and MI.

PMID- 7582244
TI  - A quantitative investigation of immunocytochemically stained blood vessels in
      normal, benign, premalignant and malignant human oral cheek epithelium.
AB  - The present study was designed to determine whether increased vascularity occurs
      during malignant transformation of human oral cheek epithelium. Nine normal (N)
      samples were taken from the resection margins of benign lesions; the pathological
      lesions were classified as chronic inflammation (CI; n = 11), fibrous hyperplasia
      (FH; n = 12), lichen planus (LIP; n = 8), dysplasia (DYS; n = 5), squamous cell
      carcinoma (SCC; n = 25; well differentiated [SCCWD]; n = 10; moderately to poorly
      differentiated [SCCMPD]; n = 15) and epithelium adjacent to carcinomas (EAC; n =
      6). Sections were stained with monoclonal antibody (mAb) against vimentin using
      an ABC immunoperoxidase technique. All blood vessels present within a depth of
      0.9 mm of lamina propria were quantified irrespective of their morphology. The
      blood vessel parameters quantified were volume density (VVBV, CT), number per
      unit area (NABV, CT), length per unit volume (LVBV, CT) and mean transverse
      sectional area (ABV). VVBV, CT increased significantly between normal and all
      pathological groups. Amongst the pathological groups, statistical differences
      were detected between CI and SCC, CI and EAC, FH and SCCWD, FH and EAC, LIP and
      SCC, LIP and EAC, DYS and SCCWD and DYS and EAC. The EAC group had the highest
      VVBV, CT and the values of NABV, CT and LVBV, CT were significantly higher in all
      the pathological groups when compared with the normal group. No significant
      differences were detected between any of the pathological group. The parameter
      ABV increased significantly between normal and DYS, FH, SCC, EAC, FH and EAC, FH
      and SCC, CI and EAC, CI and SCC, LIP and EAC and LIP and SCC. Spearman rank
      correlations detected a positive correlation between the severity of oral lesions
      and all of the blood vessel parameters. We conclude that a mAb against vimentin
      improved the identification of smaller blood vessels and the blood vessel data
      suggest that angiogenesis occurs in premalignant and malignant lesions of human
      oral cheek epithelium. Angiogenesis seems to play an essential role in sustaining
      the actively growing and transforming cells.

PMID- 7582245
TI  - HPV DNA and p53 alterations in oropharyngeal carcinomas.
AB  - We have examined a series of 37 oropharyngeal squamous cell carcinomas for the
      presence of HPV 6/11, 16, and 18 DNA by polymerase chain reaction (PCR)/Southern
      blotting and for p53 alterations by immunohistochemistry and mutation screening
      with temperature gradient gel electrophoresis (TGGE). HPV sequences were found in
      a total of 26 of 37 cancers (70.3%), most frequently HPV 16 (20/37) followed by
      HPV 18 (11/37). Double infections with HPV 16 and 18 were present in 5 tumours.
      p53 accumulation was detectable immunohistochemically in 21 of 37 carcinomas
      (56.8%). There were remarkable differences in the distribution of immunoreactive
      tumour cells in relation to the tumour grade. A mutation screening for p53 by
      TGGE, directed to the amplified exons 5-8, revealed p53 mutations in 14 of 37
      carcinomas (37.8%). Mutations in two different exons were present in 3 tumours,
      11 tumours being hit once. Exon 7 was mutated in 6 carcinomas, exons 5 and 8 in 4
      cases, and exon 6 in 3 cases. When grouping the tumours with p53 mutation
      according to their HPV state, HPV-positive cases showed slightly more mutations
      (11/26) than HPV-negative cases (3/11). Only 5 of 37 carcinomas (13.5%) contained
      neither HPV DNA nor p53 alterations. Our results indicate that high-risk HPV and
      p53 mutations frequently coexist in oropharyngeal carcinomas, in contrast to
      genital tumours, notably carcinomas of the cervix uteri. This may reflect
      different pathways in carcinogenesis in squamous cell epithelium from different
      sites.

PMID- 7582246
TI  - Morphology of the mitochondria in heat shock protein 60 deficient fibroblasts
      from mitochondrial myopathy patients. Effects of stress conditions.
AB  - We have described two mitochondrial (mt) myopathy patients with reduced
      activities of various mt enzymes associated with significantly decreased amounts
      of heat shock protein 60 (hsp60). Experimental evidence suggested that the lack
      of hsp60 was the primary defect. Since hsp60 is essential for the proper folding
      of enzyme subunits in the mt matrix a partial deficiency of this protein can
      explain the observed defects of the mitochondria. Here we report on morphological
      studies aimed at obtaining more insight into the relation between lack of hsp60
      and pathological changes of the mitochondria. Under standard culture conditions
      mitochondria in the partially hsp60 deficient fibroblasts showed profound
      morphological aberrations. In contrast, the mitochondria in fibroblasts from a
      MELAS patient and a cytochrome c oxidase-deficient patient appeared normal. Under
      stress conditions the integrity of the hsp60 deficient mitochondria declined even
      further: heat shock induced a temporary collapse of the electrochemical potential
      across the inner mt membrane, but did not affect the ultrastructure of the
      mitochondria; prolonged growth in confluent cultures resulted in decrease in mt
      number. The altered mt morphology in the hsp60 deficient cells is probably
      indicative of the severely impaired mt metabolism whereas the decreased stress
      tolerance is likely to be a direct result of paucity of the heat shock protein.
      Both variables are potentially useful in the diagnosis and molecular
      characterization of mt disorders with systemic manifestation and multiple enzyme
      deficiency.

PMID- 7582247
TI  - Demonstration of apoptosis in neuroblastoma and its relationship to tumour
      regression.
AB  - The in vivo occurrence of apoptosis in neuroblastomas was investigated.
      Histologically, a number of tumour cells showed typical apoptotic changes,
      including cell shrinkage, condensed and fragmented nuclei, eosinophilic
      cytoplasm, and absence of the inflammatory response. These cells coincided
      closely with the so-called karyorrhectic cells. An electrophoretic DNA ladder, a
      functional hallmark of apoptosis, was demonstrated in four of six tumours, and
      DNA fragmentation was detected in situ by terminal deoxytransferase-mediated nick
      end-labelling in 26 of 35 tumour specimens (74%). The labelled cell counts ranged
      from 5 to 62 per 5000 tumour cells (mean +/- SD: 15.0 +/- 14.5). Immunoperoxidase
      staining revealed that an apoptosis-suppressing protein, bcl-2, was expressed
      abundantly in advanced-stage tumours, whereas it was absent from karyorrhectic
      apoptotic cells. Several tumours with the potential for spontaneous regression
      were bcl-2-deficient. Immunostaining of the Fas receptor for apoptosis
      demonstrated that the tumour cells expressed this molecule on their cell
      surfaces. Our results provide evidence of apoptosis in neuroblastomas and suggest
      that bcl-2 and the Fas receptor may play a role in its regulatory mechanisms.

PMID- 7582248
TI  - Detection of DNA strand breaks associated with apoptosis in human brain tumors.
AB  - Apoptosis occurs spontaneously in a wide variety of neoplasms. However, it is
      difficult to detect apoptotic cells in routine histological sections because the
      cells undergoing apoptosis die singly and are then rapidly phagocytosed. Since
      DNA fragmentation is an important hallmark of apoptosis, visualization of DNA
      strand breaks in tissue sections provides the means for readily identifying
      apoptotic cells in situ. We have applied an in situ DNA strand break staining
      procedure for the quantitative estimation of apoptotic cells in surgical
      specimens of 62 different brain tumours. Positively stained apoptotic cells were
      observed in 25 (40.3%) cases and their percentage (apoptotic index) ranged from
      0.1 to 8.9. Both fragmented and condensed nuclei of apoptotic cells and apoptotic
      bodies were stained. In addition, we assessed the proliferative activity of each
      specimen by immunostaining with the MIB-1 antibody (MIB-1 index) which detects
      the cell cycle phase-dependent Ki-67 antigen. Brain tumours with higher MIB-1
      indices showed a tendency to higher apoptotic indices. The results of this study
      indicate that apoptosis occurs spontaneously in various brain tumours.

PMID- 7582249
TI  - Cell deletion by apoptosis during regression of rat parotid sialadenosis.
AB  - Enlargement of the rat parotid salivary glands was induced by repeated
      administration of isoproterenol. Mean wet weights of the treated glands increased
      steadily to 240% of control values. Following withdrawal of the drug,
      quantitative histological techniques were used to investigate the balance between
      hypertrophy, hyperplasia and apoptosis. The volume occupied by acinar cells
      relative to the total gland volume together with cytoplasmic magnitude of nuclear
      area ratios as measures of hypertrophy increased during the early experimental
      period. Similarly, serous acinar cell mitotic counts increased, indicating that
      hyperplasia had occurred. Apoptosis was demonstrated at light microscopical level
      to be the main mechanism for cell deletion as the glands returned to normal size
      and weight. The results indicate that hypertrophy and hyperplasia of serous
      acinar cells contribute to isoproterenol-induced sialadenosis. The experimental
      animal model demonstrates that these proliferative changes are completed by 48 h
      and thereafter are balanced by apoptosis as the glands recover their normal size
      and weight.

PMID- 7582250
TI  - Number and ultrastructure of epithelial cells in crypts and villi along the
      streptozotocin-diabetic small intestine: a quantitative study on the effects of
      insulin and aldose reductase inhibition.
AB  - This study has quantified the effects of insulin treatment with and without
      aldose reductase inhibitor (ponalrestat) on intestinal epithelial cell morphology
      in streptozotocin-diabetic rats. Epithelial volumes, villous and microvillous
      surface areas and mean volumes of cells (and their nuclei) in crypts and villi
      were estimated in each of four segments and in the entire intestine. We derived
      total numbers of cells, quantified the ultrastructural features of average cells
      and explored variation along the intestine and between experimental groups. In
      crypts, insulin and ponalrestat had significant effects on cell number (reduced
      towards normal values) and size (volume and apex area increased beyond normal
      values). There were interaction effects between insulin and ponalrestat for cell
      volume and apex area (insulin producing more exaggerated effects when given
      without ponalrestat). On villi, insulin and ponalrestat returned cell numbers
      towards normal values but neither treatment normalised cell size or the number
      and area of microvilli per cell. Indeed, ponalrestat increased microvillous
      number and area beyond values found in untreated diabetic animals. Again, there
      were interaction effects between insulin and ponalrestat. Patterns of segmental
      variation seen in crypts of normal rats (values tending to be higher in proximal
      or mid-intestinal regions) were not preserved, and only some of the segmental
      differences seen on villi (higher values at proximal or mid-intestinal sites)
      were maintained during therapy. Apart from reducing the abnormally high numbers
      of cells in untreated diabetic rats, these results show that insulin and
      ponalrestat treatment fail to restitute epithelial cell morphology in the small
      intestines of experimental diabetic rats.

PMID- 7582251
TI  - Endothelial regeneration during the repair process following Habu-snake venom
      induced glomerular injury.
AB  - In this study, the kinetics of glomerular endothelial cells during the repair
      process following glomerular injury was investigated in a model of mesangial
      proliferative glomerulonephritis induced by Habu-snake venom (HSV) in rats.
      Intravenous injection of HSV led to a cystic ballooning type lesion at day 1.
      Subsequently a marked segmental proliferative lesion was observed in the cystic
      areas at day 5. Thereafter cellularity decreased and reconstruction of the
      glomerular tuft was gradually observed with time. The histological structure of
      the glomeruli had almost returned to normal 21 days following HSV injection.
      After prominent depletion at day 1, the number of endothelial cells increased
      rapidly and reached a plateau at day 7, not significantly different from that of
      the control group. Morphologically endothelial cell elongation from the vascular
      pole into the cystic lesion was seen together with premature capillary formation
      in the proliferative lesion. Accompanying the reduction of mesangial expansion,
      the endothelial cells gradually formed definite capillary lumens. We conclude
      that the mesangial proliferative glomerulonephritis induced by HSV recovers to
      its original structural state and that the migration and proliferation of
      endothelial cells with accompanying capillary formation are essential for the
      repair process, in addition to mesangial cell proliferation.

PMID- 7582252
TI  - The immune reaction to heterologous serum causes osteonecrosis in rabbits.
AB  - Osteonecrosis (ON) was produced experimentally in rabbits by intravenous
      injection of horse serum. Eighty adult rabbits were used: 16 were injected twice
      with isotonic saline (Group A), 24 were injected once with saline and once with
      horse serum (Group B), and 40 were injected twice with horse serum (Group C).
      Both femurs of each rabbit were obtained from 2 h to 7 weeks after the final
      injection an were subjected to histological examination. No pathological changes
      were seen in Groups A and B. In Group C, 5 of 15 rabbits (33%) showed ON
      (necrosis of trabecula and bone marrow) in the femoral metaphysis. In Group C,
      the early major pathological findings in bone marrow are extravasation of
      erythrocytes in sinusoidal spaces and microthrombi in small arteries and
      arterioles near the lesion of extravasation. Immune complexes were demonstrated
      in the kidney within 24 h of the final injection of horse serum. The present
      study suggests that immunological reaction associated with serum sickness may
      play an important role in inducible ON and this model will contribute toward
      clarifying the pathogenesis of ON.

PMID- 7582255
TI  - Fundic gland polyps.

PMID- 7582253
TI  - The pathogenesis of so-called cardiac rhabdomyoma in swine: a histological,
      immunohistochemical and ultrastructural study.
AB  - To determine whether cardiac rhabdomyoma (CR) is a hamartoma of fetal cardiac
      myocyte, we investigated five cases of CRs that spontaneously developed in five 6
      month-old hybrid swine with histological, immunohistochemical, and
      ultrastructural techniques. The cases were four multiple and one solitary
      neoplasms, which appeared as intraventricular nodules of various sizes without
      any congenital malformations. Histologically, the large ovoid CR cells with an
      occasional spiderweb appearance showed a transition from normal-looking cardiac
      myocytes or rarely from Purkinje cells, but no mitotic figures. Besides large
      amounts of glycogen, the CR cells contained many PAS-negative, large cytoplasmic
      vacuoles filled with eosinophilic or fibrillar substance. Immunohistochemically,
      the CR cells showed intense positivity for desmin and variable positivities for
      vimentin, alpha-atrial naturiuretic peptide, and proliferating cell nuclear
      antigen. These positivities were not seen in adjacent cardiac myocytes.
      Cytokeratin was negative in the CR cells but was positive in fetal cardiac
      myocytes of early gestation. Rod-like or granular positivity for alpha-actinin in
      the CR cells was similar to that in nemaline myopathy. Ultrastructurally, the CR
      cells contained myofibrils that frequently showed myofibrillar degeneration and
      produced large intracytoplasmic vacuoles. These myofibrils often mingled with
      nemaline bodies and leptofibrils that continued to the Z bands. T-systems,
      sarcoplasmic reticulum, and intercalated discs, which are specific features of
      postnatal cardiac myocytes, were sometimes observed in the CR cells. Increase of
      glycogen and mitochondria and appearance of atrial-specific granules associated
      with the Golgi apparatus were other features noted. The present findings have not
      been reported, even in human CR. From these new observations with the recent
      report on the occurrence of CR in neonatal piglets, swine CR does not belong to
      the entity of hamartoma but may be a congenital dysplasia of the perinatal
      cardiac tissues with myofibrillar degeneration, affecting mainly cardiac myocytes
      and rarely Purkinje cells. The various immunophenotypic changes including
      proliferating cell nuclear antigen and the increase and appearance of cytoplasmic
      elements compared with mature cardiac myocytes can be interpreted as reactive or
      regenerative changes due to myofibrillar degeneration.

PMID- 7582254
TI  - Bile ductopenia following therapy with sulpiride.
AB  - We report a case of ductopenia associated with cholestatic hepatitis in a 59-year
      old woman treated for 41 years for temporal epilepsy. The patient developed
      jaundice, without any clinical or biochemical features of hypersensitivity, 10
      months after the beginning of treatment with sulpiride. Liver biopsy showed
      ballooning and acidophilic degeneration of the hepatocytes, macrophages packed
      with lipofuscin, biliary pigment in Kupffer cells, some biliary plugs, confluent
      necrosis and absence of biliary ducts in all the portal tracts. These features
      and the presence of foci of cholangiolitis suggest a destructive cholangitis as
      the pathogenetic mechanism causing ductopenia. Other causes of ductopenia were
      excluded. Sulpiride is known to produce severe cholestatic jaundice, which we
      believe is due to ductopenia. The absence of hypersensitivity and the 10-month
      latency suggest that sulpiride may cause liver damage through a toxic mechanism
      in genetically susceptible subjects.

PMID- 7582256
TI  - Comparison of gene therapy with interleukin-2 gene modified fibroblasts and tumor
      cells in the murine CT-26 model of colorectal carcinoma.
AB  - We compared the efficacy of gene therapy mediated by interleukin-2 (IL-2) gene
      modified tumor cells to gene therapy mediated by IL-2 transduced fibroblasts in
      the CT-26 model of murine colorectal carcinoma. We transduced CT-26 tumor cells
      and BALB/c 3T3 fibroblasts with three different retroviral vectors using three
      different promoters for the human IL-2 gene: DC/TKIL-2 (thymidine kinase
      promoter), LXSN-iIL2 (long terminal repeat promoter), and LNCX-iIL2
      (cytomegalovirus promoter). These transductions resulted in CT-26 and 3T3
      subclones that secreted different amounts of IL-2. Immunization of animals with
      either CT-26/IL-2 cells or with fibroblast/IL-2 cells mixed with CT-26 induced
      similar levels of immunity that protected 62-82% of animals against a subsequent
      tumor challenge with parental CT-26. However, mice developed tumors at the site
      of inoculation in 46% of the animals immunized with CT-26/IL-2 cells. In a
      separate experiment, CT-26/IL-2 cells were exposed to 6,000 cGy of gamma
      irradiation to prevent tumor growth at the site of inoculation. Although the CT
      26/IL-2 cells continued to secrete IL-2 after irradiation, they were no longer
      effective at inducing antitumor immunity. In contrast, both irradiated and
      nonirradiated fibroblast/IL-2 cells, mixed with irradiated CT-26, were equally
      effective at inducing antitumor immunity. These data suggest that in the CT-26
      model, fibroblast-mediated IL-2 gene therapy has advantages for the induction of
      antitumor immunity and abrogation of tumorigenic potential at the site of
      inoculation compared with tumor cell-mediated IL-2 gene therapy.

PMID- 7582257
TI  - A tumor-derived protein which provides T-cell costimulation through accessory
      cell activation.
AB  - A recently described tumor-derived glycoprotein, designated 90K, has been shown
      to have positive effects on the generation of cytotoxic effector cells (NK/LAK)
      from human PBMC. To determine the mechanism of these effects, we have examined
      the effects of 90K on cytokine production by human PBMC. A culture of normal PBMC
      with 90K alone did not result in IL-2 secretion; however, in coculture with
      suboptimal doses of ConA, 90K increased IL-2 secretion by PBMC. Coculture of PBMC
      with 90K and ConA also resulted in increased production of the cytokines IL-1, IL
      6, GM-CSF, and TNF alpha. T cells depleted of accessory cells failed to respond
      to ConA alone, 90K alone, or the combination of ConA and 90K, suggesting that
      this protein does not have a direct effect on T cells. However, 90K alone was
      sufficient to induce cytokine production by unfractionated PBMC (IL-1, IL-6, GM
      CSF, and TNF alpha) or by CD14-enriched PBMC (IL-1 and IL-6). In addition,
      expression of ICAM-1 was increased on a human monocytic cell line cultured with
      purified 90K in the absence of any other stimulus. This 90K-induced upregulation
      of ICAM-1 expression was accompanied by an increased accessory function of the
      monocytes, demonstrated by their ability to support ConA-induced activation of
      peripheral blood T cells. Based on the current data, we propose a model in which
      90K activates accessory cells, resulting in the secretion of cytokines and the
      expression of adhesion molecules, which in turn act as costimulatory signals for
      T-cell activation. Activated T cells then produce cytokines such as IL-2, which
      lead to a more vigorous cell-mediated immune response to tumor cells and virus
      infected cells. Thus, 90K shows promise as an immunotherapeutic reagent for
      diseases such as cancer and viral infection.

PMID- 7582259
TI  - Effects of proton irradiation on radiolabeled monoclonal antibody uptake in human
      colon tumor xenografts.
AB  - A major limitation of radiolabeled monoclonal antibodies (MAbs) for cancer
      imaging and therapy is their low accumulation within solid tumors. We, and
      others, have previously shown that pretreatment of a tumor mass with gamma
      radiation can increase the level of radiolabeled MAb at the tumor site. Unlike
      that of conventional radiation, the dose distribution of protons allows for
      increasing the dose to the cancer volume while reducing the normal tissue dose.
      The Proton Radiation Therapy Facility at LLUMC treats patients and conducts
      research. In this study, we sought to determine if preirradiation with proton
      beam can enhance the localization of radiolabeled MAb within xenotransplanted
      human colon tumors. T380 colon tumors, implanted s.c. into athymic mice, were
      subjected to proton irradiation (10 Gy, single dose) when mean tumor volume was
      125-135 mm3/group. 111In-ZCE025, a murine MAb directed against carcinoembryonic
      antigen, was injected i.p. 2 h later, and biodistribution studies were performed
      38 h thereafter. Animals irradiated with 60Co and given either 111In-ZCE025 or
      111In-MOPC21, an irrelevant MAb, served as controls. The mean percentage of
      injected radioactivity localized within tumors was highest in the group treated
      with protons + 111In-ZCE025 when expressed on a per gram basis (%ID/g = 19.3).
      Somewhat unexpectedly, higher radioactivity was also noted in the normal tissues
      of these animals compared to other groups. The mean %ID/g tumor values for those
      given 60Co + 111In-ZCE025 or the antibody alone were 12.5 and 9.0. Our data show
      that preirradiation of solid tumors increases the localization of tumor-specific
      radiolabeled MAb at the tumor site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582260
TI  - In situ interleukin-4 gene expression in cancer patients treated with genetically
      modified tumor vaccine.
AB  - Patients with advanced malignancies, participating in our ongoing phase I
      interleukin-4 (IL-4) gene therapy protocol at the Pittsburgh Cancer Institute,
      were vaccinated with irradiated autologous tumor cells together with IL-4 gene
      transduced irradiated autologous fibroblasts. The level of expression of the IL-4
      gene in cultured transduced and selected fibroblasts and in biopsies obtained
      from vaccination sites was evaluated using quantitative reverse transcription
      polymerase chain reaction (RT-PCR). The number of copies of IL-4 mRNA/ng of total
      cellular RNA was determined in the transduced fibroblasts. Good agreement was
      observed between IL-4 message expression, as determined by RT-PCR, and IL-4
      production, as determined by enzyme-linked immunosorbent assay (ELISA) in the
      fibroblast supernatants. Tissue biopsies of multiple vaccination sites were
      obtained from the patients to determine the level of gene expression in situ for
      IL-4 and Neo-r. The Neo-r gene was used as a marker for transduced fibroblasts.
      Two weeks after the first vaccination, mRNA for the IL-4 gene was still
      detectable in all tissue biopsies. The Neo-r gene was also detectable, indicating
      the presence of transduced fibroblasts in the biopsy. After the second
      vaccination, expression of the IL-4 and Neo-r genes was generally the highest on
      day 1 after vaccine administration and was considerably lower but still
      detectable on day 14 in all biopsies tested. These data indicate that autologous
      dermal fibroblasts transduced with the IL-4 and Neo-r genes and used as a source
      of IL-4 in tumor vaccine are able to express the IL-4 gene in vivo.

PMID- 7582261
TI  - Elevation of serum interleukin-6 levels before peak of serum granulocyte colony
      stimulating factor level in chemotherapy-induced myelosuppressive patients.
AB  - The aim of this study was to ascertain whether any cytokines that function in
      earlier stages of hematopoiesis also fluctuate in conjunction with granulocyte
      colony-stimulating factor (G-CSF) in chemotherapy-induced myelosuppression. A
      total of seven patients were studied. All patients received 3 days of intravenous
      injection of combination chemotherapy. Patients' absolute neutrophil count (ANC),
      platelet count, serum G-CSF, interleukin-6 (IL-6), IL-3, and IL-1 alpha were
      monitored before chemotherapy, and then daily or every other day thereafter
      during the entire treatment course until the ANC returned to normal. The results
      showed very obvious elevation of serum IL-6 level before or concurrent with the
      elevation of serum G-CSF levels at the neutrophil nadir in all seven patients.
      The rise of IL-6 also correlated with nadir platelet levels in six of seven
      patients. The finding of serum IL-6 elevation was statistically significant both
      in neutropenic and thrombocytopenic stages. Serum IL-3 level was below minimum
      detectable concentrations in all seven patients. Serum IL-1 alpha was below
      minimum detectable concentration in six patients and demonstrated no obvious
      fluctuation in the remaining patient. Therefore, the present study demonstrated
      the chronological time sequence of cytokine fluctuation, IL-6 peak before G-CSF,
      in chemotherapy-induced myelosuppression. According to this finding, when
      cytokines are used for prevention of myelosuppression or for acceleration of its
      recovery, it may be logical to use a combination of cytokines in sequence, such
      as IL-6 initially followed by G-CSF.

PMID- 7582263
TI  - [Clinical management: a new profession?Interview by Laurent Goumarre].

PMID- 7582264
TI  - [Training coordinator].

PMID- 7582258
TI  - Defective major histocompatibility complex class I expression in a sarcomatoid
      renal cell carcinoma cell line.
AB  - We studied major histocompatibility complex (MHC) class I expression in 12 tumor
      cell culture lines established from patients with metastatic renal cell carcinoma
      (RCC). In one of these cell culture lines, UOK 123, we found no surface
      expression of beta 2-microglobulin (beta 2m) and MHC class I by flow cytometry.
      Immunofluorescence staining using three different monoclonal antibodies to beta
      2m revealed no detectable beta 2m in the endoplasmic reticulum (ER), Golgi
      apparatus, cytoplasm, or on the cell surface. There was no evidence of folded
      class I molecules inside or on the surface of the cells; however, the ER stained
      intensively for unfolded class I molecules. Transient expression of beta 2m by
      UOK 123 after infection with a recombinant vaccinia virus containing the gene for
      beta 2m resulted in normal expression of both beta 2m and class I (HLA-A, B, C)
      determinants assessed by flow cytometry analysis. No expression of class I or
      beta 2m was seen with the recombinant vaccinia vector carrying a control gene.
      The inability of class I molecules to reach the cell surface is due to the
      requirement of beta 2m for proper folding and presentation of the class I MHC
      complex. The failure to assemble and express MHC class I complex on the cell
      surface renders these cells incapable of antigen presentation to cytotoxic T
      cells and provides a mechanism for escape from immune recognition by the tumor.

PMID- 7582262
TI  - Immunohistochemical features of HLA-DR antigen expression and lymphoid
      infiltrates in gastric carcinoma after low-dose interleukin-2 and mitomycin C.
AB  - We immunohistochemically evaluated lymphoid cell infiltration and HLA-DR antigen
      expression in gastric tumor tissue obtained from advanced gastric cancer patients
      1 day after the completion of the treatment with mitomycin C (MMC) 12 mg/m2 i.v.
      on day 1 and recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through
      day 8. Then the results were compared with those in 11 patients pretreated with
      MMC alone, 5 treated with IL-2 alone, and 24 untreated patients. Widespread
      lymphoid infiltration was observed in 17% of untreated tumors, 27% of MMC
      pretreated tumors, and 40% of tumors treated with IL-2 alone. However, 71% of
      carcinomas pretreated with MMC plus IL-2 exhibited widespread infiltration. The
      frequency of cases with high-grade infiltration of CD4+ cells was significantly
      higher in either group of patients treated with MMC alone or MMC plus IL-2.
      Because the CD8+ cell infiltration was not significantly altered, the ratio of
      CD4+ to CD8+ cells estimated as being > 1 was more frequently noted in patients
      given MMC alone or MMC plus IL-2, as compared with untreated control.
      Furthermore, 86% of tumors pretreated with MMC plus IL-2 exhibited positive HLA
      DR antigen expression, whereas 29% of untreated carcinomas did so. MMC or IL-2
      alone did not significantly increase HLA-DR expression. These results indicate
      that the combination of low-dose of IL-2 with MMC enhances the intensity of
      lymphoid cell infiltration in tumors, with the predominance of CD4+ cells, and
      HLA-DR antigen expression on tumor cells in patients with advanced gastric
      carcinoma.

PMID- 7582265
TI  - [The employment market: an instrument to assure mobility].

PMID- 7582266
TI  - [A new organization for better collaboration: integrated care].

PMID- 7582267
TI  - [Current tendencies in hospital management. From projected establishment to
      network management].

PMID- 7582268
TI  - [Utilization of problems with sequential solutions and in the formation of a
      nursing diagnosis].

PMID- 7582269
TI  - [Clinical teaching during training: utopia or reality? A training project at the
      night service at the Annecy Hospital center].

PMID- 7582270
TI  - [Mutations and changes. Interview by Dominique Letourneau with Etienne Caniard].

PMID- 7582271
TI  - [The solidarity employment contracts. 18 months of experience at the Nancy
      University Hospital Center].

PMID- 7582272
TI  - [Illustration and visual support: graphs].

PMID- 7582273
TI  - Empiric diagnosis of Pneumocystis carinii pneumonia. Questions of accuracy and
      equity.

PMID- 7582274
TI  - Relationship between procedures and health insurance for critically ill patients
      with Pneumocystis carinii pneumonia.
AB  - The objective of the present study was to assess the association between type of
      health insurance coverage and use of diagnostic tests and therapies among
      patients with AIDS-related Pneumocystis carinii pneumonia (PCP). Fifty-six
      private, public, and community hospitals in Chicago, Los Angeles, and Miami were
      selected for the study, and the charts of 890 patients with empirically treated
      or cytologically confirmed PCP, hospitalized during 1987 to 1990 were
      retrospectively reviewed. Patients were classified by insurance status: self-pay
      (n = 56), Medicaid (n = 254), or private insurance, including health maintenance
      organizations and Medicare (n = 580). Primary outcomes were the use and timing of
      bronchoscopy, the type and timing of PCP therapy, and in-hospital mortality. The
      results indicate that Medicaid patients were less likely than privately insured
      patients to undergo bronchoscopy (relative odds = 0.61; 95% CI = 0.40, 0.93; p =
      0.02) or to have their diagnosis of PCP confirmed (relative odds = 0.51; 95% CI =
      0.33, 0.77), after adjusting for patient, severity of illness, and hospital
      characteristics. Medicaid patients were approximately three-fourths more likely
      than privately insured patients (relative odds = 1.73; 95% CI = 1.01, 2.96; p =
      0.04) to die in-hospital, after adjusting for patient, severity of illness, and
      hospital characteristics. However, with further adjustment for confirmation of
      PCP, Medicaid patients no longer had a significantly higher likelihood of dying
      in-hospital. We conclude that Medicaid patients are less likely to receive
      diagnostic bronchoscopy than privately insured or self-insured patients, more
      likely to be empirically treated for PCP, and more likely to die in
      hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582275
TI  - Effect of a leukotriene B4 receptor antagonist SC-53228 on ozone-induced airway
      hyperresponsiveness and inflammation in dogs.
AB  - The importance of the potent neutrophil chemoattractant leukotriene (LT)B4 in
      causing ozone-induced bronchoconstriction, airway inflammation, and airway
      hyperresponsiveness in dogs was studied using the LTB4-receptor antagonist SC
      53228. Seven dogs from random sources were studied three times, at least 2 wk
      apart. On each occasion, acetylcholine (Ach) airway responsiveness was measured
      before and 1 h after ozone (3 ppm, 30 min) or dry air inhalation, followed by a
      bronchoalveolar lavage (BAL). On the first day, dogs were treated with SC-53228
      (0.4 mg/kg intravenously) followed by a continuous intravenous infusion of 1.2
      mg/kg/h before ozone inhalation. On the other two days, diluent was infused
      followed by ozone or dry air inhalation. Cell counts were measured in BAL and
      cell activation was measured by spontaneous and by phorbol myristate acetate
      stimulated (PMA) (2.4 mumol/L) oxygen radical release, measured from washed BAL
      cells (4 x 10(6) cells) by lucigenin-enhanced chemiluminescence. Ozone inhalation
      caused bronchoconstriction and airway hyperresponsiveness. SC-53228 inhibited the
      ozone-induced airway hyperresponsiveness (p = 0.006), but not the
      bronchoconstriction. Spontaneous (p = 0.004) and PMA-stimulated (p = 0.04)
      lucigenin-enhanced chemiluminescence were increased after ozone inhalation. The
      ozone-induced increases in PMA-stimulated chemiluminescence were significantly
      attenuated by treatment with SC-53228 (p = 0.04). These results suggest that LTB4
      is involved in the pathogenesis of ozone-induced airway hyperresponsiveness,
      possibly through activation of airway inflammatory cell.

PMID- 7582276
TI  - Pharmacologic characterization of endothelin receptor responses in the isolated
      perfused rat lung.
AB  - Endothelin receptor subtypes were characterized in isolated perfused rat lungs
      using the peptide ETA-receptor antagonists BQ 610 and BQ 123, the nonpeptide
      mixed ETA-/ETB-receptor antagonist bosentan, and the ETB-receptor agonist IRL
      1620. Intra-arterial injection of 1 nmol IRL 1620 caused an enhanced reduction in
      pulmonary conductance compared with 1 nmol endothelin (ET-1) or 0.33 nmol IRL
      1620. Pretreatment of lungs with BQ 610, BQ 123, or bosentan aggravated the
      bronchoconstriction induced by 1 nmol ET-1 so that it was comparable to that
      induced by 1 nmol IRL 1620. Although perfusion with 1 nmol IRL 1620 had only
      minor effects on vascular conductance, 1 nmol ET-1 caused a marked decrease in
      this parameter. This vasonconstriction was prevented by BQ 610, BQ 123, or
      bosentan. High concentrations of the stable prostacyclin metabolite, 6-keto-PGF1
      alpha, were found in the perfusate of lungs treated with 1 nmol IRL 1620 or 1
      nmol ET-1. The ET-1-induced release of 6-keto-PGF1 alpha was blocked by bosentan,
      but not by BQ 610. ET-1, but not IRL 1620, provoked the release of thromboxane
      B2. The main effect of ETA-receptor stimulation is vasoconstriction, whereas ETB
      receptor stimulation causes bronchoconstriction. Both actions, however, are
      attenuated by the other receptor, i.e., the ETA-induced vasoconstriction is
      attenuated by ETB-receptor-induced release of vasodilators such as prostacyclin,
      whereas the ETB-receptor-induced bronchoconstriction is attenuated by an unknown
      ETA-receptor-dependent bronchodilatory mechanism.

PMID- 7582277
TI  - Single, high-dose intramuscular triamcinolone acetonide versus weekly oral
      methotrexate in life-threatening asthma: a double-blind study.
AB  - Effective and less toxic treatments are needed for patients with severe, steroid
      dependent asthma. Both low-dose oral methotrexate and high-dose intramuscular
      triamcinolone have been recommended for these patients. We compared the effects
      of these two medications on pulmonary function, peak flow rates, airway
      reactivity, oral steroid use, emergency room (ER) visits, and hospitalizations in
      patients with steroid-dependent, life-threatening asthma. In a randomized,
      placebo-controlled, double-blind study, we investigated 19 such patients. Six of
      the patients (Group I) received a single dose of 360 mg triamcinolone
      intramuscularly with placebo methotrexate; seven patients (Group II) received
      placebo triamcinolone followed by low-dose oral methotrexate (a first dose of 7.5
      mg followed by 15 mg weekly); and six patients (Group III) received placebo
      triamcinolone with placebo methotrexate. All patients used the same high-dose
      inhaled steroids. The patients took tapering courses of oral steroids when
      needed, but attempted to reduce their oral steroid use whenever possible.
      Methacholine challenge testing was performed every 6 wk, pulmonary function tests
      every 4 wk, and home peak-flow measurements twice daily. Oral steroid use, ER
      visits, and hospitalizations were also monitored. The patients in the
      triamcinolone treatment group showed a significant and sustained increase in home
      peak-flow rates, and their FEV1 persistently improved by a mean of 40% (p <
      0.05), whereas the FEV1 of the patients in the methotrexate treatment and placebo
      groups remained near baseline. The PC20 in the triamcinolone group increased
      progressively (p > 0.05), and the improvements in total mean reactivity were
      greater in this group than in either of the other two groups (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582278
TI  - Fluticasone propionate reduces oral prednisone use while it improves asthma
      control and quality of life.
AB  - This study examined the ability of fluticasone propionate aerosol to reduce oral
      prednisone requirements in patients with severe asthma. Ninety-six patients
      dependent on oral prednisone were treated for 16 wk with placebo or fluticasone
      propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral
      prednisone was adjusted weekly according to predetermined criteria. A total of
      69% and 88% of patients treated with fluticasone propionate 750 and 1,000
      micrograms twice daily, respectively, compared with 3% of placebo-treated
      patients used no prednisone by the end of the study. In the fluticasone
      propionate groups, FEV1 and peak expiratory flow rates at the last evaluable
      visit/date improved and the number of night awakenings and symptomatic albuterol
      use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms
      improved in the groups receiving fluticasone propionate but not in the placebo
      group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it
      improved some dimensions of health-related quality of life measured using a
      standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms
      twice daily) effectively and safely allowed most asthmatics dependent on oral
      corticosteroids to reduce or eliminate oral prednisone use while improving
      pulmonary function and quality of life.

PMID- 7582279
TI  - Cytokines in bronchoalveolar lavage fluid of patients with nocturnal asthma.
AB  - Airflow obstruction can have a circadian pattern with nocturnal worsening. Airway
      inflammation is a cardinal feature of asthma, and it has been shown to increase
      at night in association with the decline in pulmonary function. Although the
      mechanisms regulating enhanced airway inflammation in asthma at night have yet to
      be ascertained, we hypothesized that circadian variation in cytokine expression
      or production is an important factor in the development of nocturnal airflow
      limitation. To investigate this possibility, spirometry and bronchoscopy were
      performed; the bronchoalveolar lavage (BAL) fluid obtained at 4:00 A.M. and at
      4:00 P.M. were measured for IL-1 beta in asthmatics with (n = 5) and without (n =
      9) nocturnal asthma. In addition, the activity of IL-3, IL-5, and GM-CSF was
      measured using a biologic assay (eosinophil survival-enhancing activity). BAL
      fluid concentrations of IL-1 beta were significantly greater at 4:00 A.M. than at
      4:00 P.M. (1.14 +/- 0.6 versus 0.7 +/- 0.6 pg/ml; p = 0.05) in asthmatics with
      nocturnal airflow obstruction. Moreover, IL-1 beta levels at 4:00 A.M. tended to
      be higher in subjects with nocturnal asthma than in those without nighttime
      airflow reduction (1.14 +/- 0.6 versus 0.3 +/- 0.4 pg/ml; p = 0.1). On the other
      hand, eosinophil survival-enhancing activity in BAL fluid, which is usually
      associated with IL-3, IL-5, or GM-CSF, was not detected in relationship to
      nocturnal asthma. Because IL-1 beta can activate air-space cells, particularly
      alveolar macrophages, we propose that an increased release of this cytokine is a
      significant contributor to nocturnal airway inflammation and obstruction in
      asthma.

PMID- 7582280
TI  - Airway obstruction in boilermakers exposed to fuel oil ash. A prospective
      investigation.
AB  - We prospectively investigated the lower airway response in boilermakers
      overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean
      age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge
      tests were performed before beginning the boiler overhaul; postexposure tests
      were performed after approximately 4 wk of work on the boiler. Exposure to
      particulates with an aerodynamic diameter of 10 microns and smaller (PM10) and
      respirable vanadium dust were estimated using daily work diaries and a personal
      sampling device for respirable particles. Using these estimates, we calculated
      average and peak exposure between pre- and postexposure tests for each subject.
      The average PM10 concentration ranged from 1.44 to 6.69 mg/m3, with a mean (SD)
      of 3.22 (1.42) mg/m3; the average vanadium concentration ranged from 2.2 to 31.3,
      with a mean (SD) of 12.2 (9.1) micrograms/m3. The mean postexposure fall in FEV1
      was 140 +/- 160 ml (p < 0.01); 24 of 26 subjects had a drop in FEV1. For each
      subject, the adjusted change in FEV1 (delta FEV1.adj) was calculated by dividing
      the change in FEV1 by the average of the pre- and postexposure FEV1 values. The
      delta FEV1.adj was regressed, controlling age and current smoking status, on
      average and peak exposure to both PM10 and vanadium. There was a dose-response
      relationship between average and peak PM10 exposure and delta FEV1.adj: beta = 
      0.91% per mg/m3, p = 0.08 and beta = -1.03% per mg/m3, p = 0.03, respectively.
      However, there was no relationship between delta FEV1.adj and respirable vanadium
      dust concentration. Furthermore, there was no postexposure change in nonspecific
      airway responsiveness. In summary, we found a significant fall in FEV1 and a dose
      response relationship between delta FEV1.adj and average and peak PM10
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582281
TI  - Interaction of inhaled beta 2 agonist and inhaled corticosteroid on airway
      responsiveness to allergen and methacholine.
AB  - Regular treatment with salbutamol increases airway responsiveness to allergen but
      not to methacholine and produces tolerance to the bronchoprotective effect of
      salbutamol. The current study addresses the effect of inhaled corticosteroid on
      these aspects of regular beta 2 agonist use. A group of 13 atopic asthmatic
      subjects free from all asthma medications and remote from allergen exposure were
      studied. We used a double-blind, random-order, crossover study to compare four 1
      wk treatment periods with > or = 1 wk washout: placebo, salbutamol, 200
      micrograms four times per day, budesonide, 400 micrograms four times per day, and
      the combination of salbutamol and budesonide. We measured the methacholine PC20
      and the methacholine dose shift produced acutely by 200 micrograms salbutamol
      after 7 d and the allergen PC15 after 8 d treatment. Blinded medications were
      withheld for 8 to 10 h before measurements. The methacholine PC20 was not
      affected by regular salbutamol but increased significantly (p < 0.014) after both
      budesonide-containing regimens. Neither the dose shift nor its significant
      reduction by regularly used beta 2 agonist were influenced by the inhaled
      corticosteroid. The four allergen PC15 values were significantly different from
      each other. Compared with placebo, the allergen PC15 was 0.6 doubling doses lower
      after salbutamol (p = 0.021) and 1.3 doubling doses higher after budesonide (p <
      0.001); the allergen PC15 was reduced by 0.53 doubling doses from this new
      baseline (p = 0.039) when salbutamol and budesonide were used together.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582282
TI  - Rhinovirus inhalation causes long-lasting excessive airway narrowing in response
      to methacholine in asthmatic subjects in vivo.
AB  - Exacerbations of asthma are often associated with respiratory infections, and
      particularly those caused by rhinovirus. The causative role of rhinovirus in
      these acute episodes is still unclear, since it has not been determined whether
      or not infection with the virus promotes excessive airway narrowing in asthma. We
      tested the hypothesis that experimental infection with inhaled wild-type
      rhinovirus 16 (RV16) increases the maximal degree of airway narrowing in response
      to bronchoconstrictor stimuli in patients with mild to moderate asthma. Fourteen
      nonsmoking subjects with atopic asthma and normal FEV1 values participated in a
      double-blind, placebo-controlled, parallel study. A total dose of 3 x 10(4) of
      the 50% tissue-culture-infective dose (TCID50) of RV16 or a placebo was
      administered by pipette, atomizer, and nebulizer in equal doses into both
      nostrils on two consecutive days. Dose-response curves for inhaled methacholine
      were recorded 1 d before and 2, 7, and 15 d after RV16 infection or placebo. The
      response to methacholine was measured by the percent decrease in FEV1, and the
      maximal degree of airway narrowing was expressed by the average response on the
      plateau of the dose-response curve. In the seven subjects receiving the virus,
      RV16 infection was confirmed in nasal washings and/or by an increase in antibody
      titer, whereas these tests were negative in the placebo group. There was no
      significant change in baseline FEV1 during the study in either group (p =
      0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582283
TI  - The relationship between parental and children's serum IgE and asthma.
AB  - This paper examines the familial aggregation of physician-diagnosed asthma in
      relation to the age- and sex-standardized total serum IgE levels of children and
      their parents in a sample of the general population in Tucson, Arizona, that has
      been followed in a longitudinal study for over 20 yr. There were 591 nuclear
      families containing 1,177 children who provided information about the presence or
      absence of a physician diagnosis of asthma. The serum IgE data were less
      complete: both parents and one or more of their children in 251 of the nuclear
      families, containing 468 children, had serum IgE levels measured. There was a
      very strong tendency for asthmatic patients to have asthmatic children, but only
      a small part of this appeared to be related to the familial aggregation of total
      serum IgE. In the absence of an asthmatic parent, there was a slight but
      significantly higher prevalence of asthma in children of whom both parents had
      IgE levels in the highest tertile. Very high rates of children's asthma depended
      on there being an asthmatic parent who also had at least moderate levels of serum
      IgE. It was also shown that asthmatic children have considerably higher total IgE
      levels than would be expected on the basis of their parents' IgE levels alone.
      The data appear compatible with several familial-aggregation hypotheses and a
      strong environmental influence determining which children are likely to develop
      asthma. We speculate that the inflammation in the airways of asthmatic patients
      itself tends to increase the serum IgE level, possibly secondary to mediators
      that it generates.

PMID- 7582288
TI  - Lymphatic release of cytokines during acute lung injury complicating severe
      pancreatitis.
AB  - In severe acute pancreatitis (SAP), the mechanisms leading to adult respiratory
      distress syndrome (ARDS) are usually attributed to the release of active enzymes
      and vasoactive substances from the pancreas. Thoracic duct drainage has been
      proposed as a means of removing the portion of these substances that drain
      through retroperitoneal lymphatics before they reach the systemic circulation.
      This technique was used in six patients with ARDS complicating SAP. The levels of
      proinflammatory cytokines (tumor necrosis factor-alpha [TNF alpha], interleukin-1
      [IL-1], and interleukin-6 [IL-6]), neutrophil enzymes (myeloperoxidase and
      lactoferrin), and pancreatic enzymes (amylase, lipase and trypsin) were measured
      in plasma and lymph in the first 24 h of ARDS and then on Day 2, Day 4, and at
      the end of the drainage (Day 8). High plasma concentrations of these products
      were measured. A moderate lymph-to-plasma gradient was observed for IL-6, lipase,
      and trypsin, while similar levels in plasma and lymph were recorded for the other
      substances. Plasma levels of pancreatic enzymes were weakly correlated with the
      lung injury score and lymph level of cytokines. These results suggest that in
      patients with ARDS due to SAP, cytokines as well as pancreatic enzymes could
      contribute to the development of the lung injury, and that lymphatics are
      potential vectors of these mediators.

PMID- 7582287
TI  - Prospective validation of an acute respiratory distress syndrome predictive
      score.
AB  - We derived an Acute Respiratory Distress Syndrome Score (ARDS Score) from
      previously described training set data. To validate its diagnostic accuracy for
      identifying a complicated course (early death or prolonged intubation) in acute
      lung injury, 50 patients were prospectively scored using an ARDS Score decision
      threshold of > or = 2.5 to discriminate between an uncomplicated (successful
      extubation after < or = 14 d) and complicated course. Predictor factors
      incorporated in the ARDS Score were collected on Day 4 and Day 7 of ARDS and
      included PaO2/PAO2 ratio, required positive end-expiratory pressure (PEEP), and
      chest radiograph progression. The diagnostic accuracy of the ARDS Score for
      determining a complicated course as well as overall survival was compared with
      three other available indices. Using receiver operating characteristic (ROC)
      analysis, the ARDS Score and Lung Injury Score (LIS) had the greatest diagnostic
      accuracy for determining a complicated course, but the Simplified Acute
      Physiology Score (SAPS Score) (score > or = 14) more accurately identified
      survival. The LIS components of static respiratory system compliance (Crs) and
      chest radiograph description did not differ between patient groups. The
      interobserver concordance of the dynamic chest radiograph interpretation included
      in the ARDS Score was significant (p < 0.05). We conclude that the previously
      derived ARDS Score has valid diagnostic accuracy for identifying patients with
      ARDS who will follow a complicated course.

PMID- 7582286
TI  - Collagenase increases shortening of human bronchial smooth muscle in vitro.
AB  - The recent demonstration of increased shortening of asthmatic airway smooth
      muscle could result from increased contractility of the muscle itself or from a
      decreased load that must be overcome by the smooth muscle to shorten. To evaluate
      the role of smooth muscle-associated extracellular matrix in limiting smooth
      muscle responses, we investigated the effect of collagenase on the mechanical
      responses of human bronchial smooth muscle strips. Contractile responses of
      second- to fourth-generation bronchi were evoked by electrical field stimulation,
      and measurements of length and tension were made at preloads between 0 and 2.5 g.
      The passive tension, active isometric, and isotonic responses were obtained at
      each preload before and after 90 min of incubation with 20 U/ml collagenase.
      Shortening to 10(-4) M histamine was also measured. Collagenase treatment caused
      a significant decrease in passive tension, with the most pronounced change
      occurring below Lmax (optimal length for force generation). At optimal lengths
      for shortening, the degree of shortening, expressed as a percentage of starting
      length, increased significantly from 8.9 +/- 1.4% before to 13.8 +/- 2.9% after
      collagenase treatment (n = 7) (p < 0.02). Shortening to histamine also increased
      from 14.3 +/- 2.5% before to 23.5 +/- 5.3% after collagenase treatment (n = 7) (p
      < 0.02). These results suggest that degradation of the collagenous matrix
      surrounding muscle in the airway wall reduces the load on the muscle, allowing
      increased smooth muscle shortening.

PMID- 7582284
TI  - Acute effects of ozone on the pulmonary function of exercising schoolchildren
      from Mexico City.
AB  - The acute effects of ozone (O3) on the change in lung function before and after
      exercise was assessed in 22 boys and 18 girls from 7 1/2 to 11 yr of age tested
      up to eight times over a 1 1/2-yr period outdoors (under a tarpaulin) at a school
      in Mexico City. Ozone and particulates were monitored at an adjacent government
      station, in the school yard, and under the tarp. Subjects were selected to
      oversample children with chronic respiratory symptoms, although children with
      active asthma under regular medication or FEV1 < 80% predicted were excluded. Of
      the participants, 21 had chronic cough, chronic phlegm, or ever wheeze with colds
      or apart from colds. Children performed two cycles of treadmill exercise (15 min)
      and rest (15 min) for a total of 1 h of intermittent exercise. Most subjects
      attained the target minute ventilation of 35 L/min/m2. Subjects exercised
      alternately during low ozone hours (8:00-10:00 A.M.) and during peak O3 hours
      (12:00-2:00 P.M.), to assure a range of exposures. On 85% of exercise days, the
      maximum daily 1-h average for ambient O3 exceeded the Mexican guideline of 110
      parts per billion (ppb). O3 exposure during the hour of exercise was divided into
      quintiles, and the response was adjusted for repeated measures, subject having a
      cold, and prior outdoor exercise. Ambient O3 in the fifth quintile (mean = 229
      ppb) was associated with a percentage change in FVC (-1.43% +/- 0.70), FEV1 (
      2.85% +/- 0.79), FEF25-75% (-6.32 +/- 1.87) and FEV1 (-1.41% +/- 0.46).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582289
TI  - Hypocapnia-induced ventilation/perfusion mismatch: a direct CO2 or pH-mediated
      effect?
AB  - The purpose of this study was to determine whether the increased
      ventilation/perfusion (VA/Q) mismatch caused by hypocapnic hyperventilation in
      dogs (J. Appl. Physiol. 1993; 74:1306-1314) is a direct CO2 or a pH-mediated
      effect. From an initial state of hyperventilated respiratory alkalosis (FIO2 =
      0.21, VT = 18 ml/kg, RR = 35), we studied the changes in VA/Q distributions,
      respiratory gas exchange, and hemodynamics when the acid-base status of the dogs
      was manipulated by combinations of acid or alkali infusion with or without CO2
      inhalation. In this manner, we studied respiratory alkalosis (high pH, low PCO2),
      normalized acid-base status (normal pH, normal PCO2), metabolic acidosis (low pH,
      normal PCO2), metabolic alkalosis (high pH, normal PCO2), and a mixed respiratory
      alkalosis and metabolic acidosis (normal pH, low PCO2). Gas exchange was
      evaluated using the multiple inert gas elimination technique. PaO2 was reduced
      and VA/Q heterogeneity was increased in all conditions defined by a high pH,
      independent of the PCO2 (respiratory alkalosis and metabolic alkalosis). In
      contrast, PaO2 and VA/Q heterogeneity was unchanged in conditions defined by
      either a normal or low pH (normalized acid-base status, mixed respiratory
      alkalosis and metabolic acidosis, and metabolic acidosis). Therefore, we conclude
      that hypocapnia-induced VA/Q mismatch in hyperventilated dogs is pH-mediated and
      is not a function of PCO2 per se.

PMID- 7582290
TI  - ELISA technique for quantification of surfactant protein B (SP-B) in
      bronchoalveolar lavage fluid.
AB  - Surfactant protein B (SP-B) is one of the essential constituents of the alveolar
      surfactant system, presenting mainly in the form of SP-B dimer. The measurement
      of this molecule in biologic samples has been hampered by its extreme
      hydrophobicity and intimate association with surfactant lipids. We developed a
      solid-phase, adsorption-based enzyme-linked immunosorbent assay (ELISA) technique
      for the quantification of SP-B in aqueous solutions. The ELISA employs the
      hydrophobicity of SP-B for direct binding of this compound to polystyrol
      immunosorbent plates. Samples are mixed with propanol (1:1 vol/vol) to achieve a
      homogeneous dispersion of their lipophilic constituents prior to adsorption to
      the wells. After fluid removal by evaporation, trifluoroethanol is added to
      optimize SP-B-polystyrol binding, and is then removed, again by evaporation.
      Subsequent washing procedures (diisopropyl-ether/butanol; Tween 20 in phosphate
      buffered saline [PBS]) selectively remove phospholipids. Solid phase-bound SP-B
      is detected by a monoclonal mouse antibody against porcine SP-B, cross-reacting
      with the apoprotein of human origin. For amplification, a biotinylated anti-mouse
      antibody and the avidin/biotin-peroxidase technique are used. Steep calibration
      curves with an excellent reproducibility are obtained for SP-B dimer (range:
      0.3125 to 40 ng/well), either introduced directly into the immunosorbent-plate
      wells or previously admixed with synthetic phospholipid mixtures. SP-B monomer is
      detected with approximately 10% efficiency as compared with the dimer (wt/wt).
      Cross-reactivities with human SP-A and SP-C or albumin are negligible.
      Experiments with spiking of human bronchoalveolar lavage fluid (BAL) samples with
      different quantities of SP-B dimer revealed virtually complete apoprotein
      recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582285
TI  - Role of airway eosinophils in the development of allergen-induced airway
      hyperresponsiveness in dogs.
AB  - The role of the eosinophil in the development of allergen-induced airway
      hyperresponsiveness is uncertain. We examined whether the development of airway
      hyperresponsiveness in 17 dogs after inhalation of Ascaris suum allergen (10(-6)
      to 10(-2) weight/volume [w/v]) was associated with increases in the number and
      level of activation of eosinophils before and after allergen inhalation. Airway
      responsiveness to inhaled acetylcholine was measured before and 24 h after
      Ascaris inhalation. Eosinophil number was assessed by bronchoalveolar lavage
      performed 1 wk before allergen inhalation and 15 min after the 24 h acetylcholine
      challenge. Dogs that developed Ascaris-induced airway hyperresponsiveness (n = 8)
      had a significantly greater number of bronchoalveolar lavage eosinophils before
      allergen inhalation (mean +/- SEM: 4.6 +/- 1.94 x 10(4) cells/ml) than dogs that
      did not become hyperresponsive (n = 9) (1.2 +/- 0.81 x 10(4) cells/ml) (p =
      0.03). Ascaris-induced airway hyperresponsiveness, measured 24 h after allergen
      inhalation, was not associated with increases in eosinophil number after allergen
      challenge. These results suggest that the presence of airway eosinophils before
      allergen inhalation is necessary for the development of allergen-induced airway
      hyperresponsiveness.

PMID- 7582293
TI  - Clinical isolates of Mycobacterium simiae in San Antonio, Texas. An 11-yr review.
AB  - During a period of 11 yr (1983-1993) 137 clinical isolates of Mycobacterium
      simiae obtained from 75 patients were identified in a University hospital in San
      Antonio, Texas. One hundred twenty-eight isolates (93%) were from a pulmonary
      source, four (3%) from blood, and five from other sites including skin, urine,
      lymph node, bone marrow, and brain. Of 62 evaluable patients, six (10%) had
      definite infection, nine (14%) had probable disease, and 48 (76%) were thought to
      be colonized. During the last 2 yr of the study (1992 and 1993), M. simiae became
      the second most frequently isolated nontuberculous mycobacterium at this
      institution surpassed only by Mycobacterium avium complex. There are limited data
      about effective treatment for this multidrug-resistant organism. New macrolides,
      quinolones, ethambutol, clofazimine, and aminoglycosides are promising
      therapeutic agents.

PMID- 7582292
TI  - GRO alpha and interleukin-8 in Pneumocystis carinii or bacterial pneumonia and
      adult respiratory distress syndrome.
AB  - Polymorphonuclear leukocytes (PMN) are the predominant inflammatory cells
      recruited in acute lung injury. This study compares the concentration of
      interleukin-8 (IL-8) to those of GRO alpha, both of which are CXC chemokines, in
      bronchoalveolar lavage fluid (BALF) in three acute pathologic states: bacterial
      pneumonia (BPN); adult respiratory distress syndrome (ARDS); and Pneumocystis
      carinii pneumonia (PCP). Levels of both IL-8 and GRO alpha were below 5 pg/ml in
      16 nonsmoking volunteers who served as controls. Despite more than twice as many
      neutrophils in the BALF of the BPN group (n = 12) than in the group with ARDS (n
      = 13), both groups had similar levels of IL-8, of 569 +/- 120 pg/ml and 507 +/-
      96 pg/ml, respectively. The GRO alpha concentrations in the BPN and ARDS patients
      were respectively 3.3 and 3.4 times those of IL-8, reaching 1,870 +/- 314 pg/ml
      for the BPN and 1,699 +/- 377 for the ARDS patients. In the PCP group (n = 48, 45
      human immunodeficiency virus [HIV]-positive, 3 HIV-negative), GRO alpha levels
      (897 +/- 172 pg/ml) were sevenfold higher than IL-8 levels (123 +/- 40 pg/ml). In
      all pathologic states there was a good correlation between GRO alpha and IL-8 (r
      = 0.53, p = 0.0001). GRO alpha or IL-8 both correlate with the absolute
      neutrophil number/ml when all groups were studied together (r = 0.52, p =
      0.0001). Only in the PCP and ARDS groups did IL-8 correlate with the PMN
      number.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582291
TI  - Effects of enteral and parenteral nutrition on gut mucosal permeability in the
      critically ill.
AB  - The use of total parenteral nutrition (TPN), in the critically ill, may be
      associated with the translocation of bacteria and their products from the lumen
      of the gastrointestinal tract (GIT) to the systemic circulation. We report a
      study comparing the effects of TPN and enteral nutrition (EN) on GIT function.
      Twenty-four critically ill patients were randomly allocated to receive TPN or EN.
      GIT absorption was measured by urinary recovery of D-xylose and 3-O-methyl-D
      glucose (3O MG) after enteral administration. The ratio between urinary recovery
      of lactulose and L-rhamnose (L/R) was used to measure GIT mucosal permeability.
      Results are expressed as the percentage of enterally administered saccharide
      recovered. Measurements were performed at entry to the study and on every
      subsequent third day. Baseline recovery of D-xylose (5.95 +/- 1.61%, EN; 6.56 +/-
      3.38%, TPN) and 3O MG (12.35 +/- 4.06%, EN; 7.96 +/- 4.19%, TPN) was
      significantly lower than for the controls (35.03 +/- 1.40% for D-xylose, p < 0.05
      compared to both study groups; 49.20 +/- 1.98% for 3O MG, p < 0.05 compared to
      both study groups). Baseline L/R ratio was increased (0.292 +/- 0.072%, EN; 0.463
      +/- 0.118%, TPN) compared with the controls (0.038 +/- 0.006%, p < 0.05 compared
      to both study groups). In the EN group, the L/R ratio displayed a progressive,
      significant fall. In the TPN group, no significant change in the L/R ratio
      occurred. This study demonstrates that GIT dysfunction is evident in critically
      ill patients and suggests that loss of GIT mucosal integrity is reversed by the
      institution of EN.

PMID- 7582296
TI  - Comparison of sputum induction with fiber-optic bronchoscopy in the diagnosis of
      tuberculosis.
AB  - Microbiologic confirmation of pulmonary tuberculosis among patients whose sputum
      smear is negative is increasingly important because of greater incidence among
      immunocompromised hosts and emergence of drug-resistant strains. We prospectively
      compared sputum induction to fiber-optic bronchoscopy in the diagnosis of such
      patients. Consecutive patients referred for investigation of possible active
      pulmonary tuberculosis underwent sputum induction with hypertonic saline
      delivered by an ultrasonic nebulizer between 2 and 48 h before transnasal fiber
      optic bronchoscopy. All specimens were examined for acid-fast bacilli with
      fluorescent microscopy and cultured for mycobacteria. Clinical information was
      abstracted from patient records, and X-rays were reviewed by two blinded readers.
      Among 101 participants, sputum induction was well-tolerated without complications
      and provided adequate samples in 93. Sensitivity of direct acid-fast bacilli
      smear of specimens from both techniques was low. Sensitivity and negative
      predictive value of culture from bronchoscopy specimens was 73% and 91% compared
      with 87% and 96%, respectively, for sputum induction when a specimen was
      obtained. Direct costs for bronchoscopy totaled Canadian $187.60 compared with
      Canadian $22.22 for sputum induction. Sputum induction was well-tolerated, low
      cost, and provided the same, if not better, diagnostic yield compared with
      bronchoscopy in the diagnosis of smear-negative pulmonary tuberculosis.

PMID- 7582299
TI  - Elevated serum hepatocyte growth factor/scatter factor levels in inflammatory
      lung disease.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in
      tissue repair in liver and renal damage. The clinical significance of this growth
      factor in these diseases has also been reported. The lung is one of the major
      sources of HGF/SF; because of this, we investigated serum HGF/SF levels in 26
      patients with inflammatory lung disease (15 with interstitial pneumonitis [IP],
      11 with bacterial pneumonia [BP]) by enzyme-linked immunosorbent assay. As
      controls, we measured HGF/SF in the serum of 13 stable outpatients with chronic
      respiratory failure. All patients had no significant liver or renal dysfunction.
      Serum HGF/SF levels were significantly elevated in patients with IP (1.16 +/-
      0.22 ng/ml) or BP (0.96 +/- 0.27 ng/ml) compared with those in the control
      subjects (0.29 +/- 0.03 ng/ml, both p < 0.01). Serum HGF/SF levels in 14 healthy
      subjects were also studied, and the results (0.30 +/- 0.02 ng/ml) were not
      remarkably different from those of the control subjects. There were no
      significant correlations between serum HGF/SF levels and C-reactive protein and
      lactate dehydrogenase. Serum HGF/SF levels in the surviving patients rapidly
      decreased with treatment, but they did not change in the patients who ultimately
      died. Our results demonstrate the clinical significance of serum HGF/SF level as
      a useful indicator of prognosis in inflammatory lung disease.

PMID- 7582295
TI  - Changing heat and moisture exchangers every 48 hours rather than 24 hours does
      not affect their efficacy and the incidence of nosocomial pneumonia.
AB  - Heat and moisture exchangers (HME) (Dar-Hygrobac II, Peters) can safely be used
      every 24 h for long-term mechanical ventilation and provide a cost-saving
      alternative to heated humidifiers. We have prospectively determined whether
      changing HMEs every 48 h only affects their clinical and bacteriological
      efficiency in a series of consecutive nonselected ICU patients requiring long
      term mechanical ventilation. Two consecutive periods were compared. During period
      1, HMEs were replaced every day; during period 2, they were changed every 48 h.
      Patients from the two periods were similar in terms of age and indication for and
      overall duration of MV (10 +/- 8.6 versus 10 +/- 9 d, p = 0.9). Minute
      ventilation and maximum values for peak airway pressure were identical during the
      two periods. These values were also identical after 1 and 2 d of HME use during
      period 2, indicating that HME resistance was not increased by prolonged use.
      Obstruction of the tracheal tube occurred only once in a period 1 patient. The
      results of quantitative cultures indicate that the maximum and mean levels of
      bacterial colonization during the two periods were similar for the pharynx,
      trachea, Y-connector, patient, and ventilator side of the HME. More importantly,
      the incidence of nosocomial pneumonia was similar during the two periods (6/61
      versus 8/68, p = 0.7). Thus, prolonged HME use is safe and provides a substantial
      reduction in the cost of mechanical ventilation.

PMID- 7582297
TI  - Does the protective effect of neonatal BCG correlate with vaccine-induced
      tuberculin reaction?
AB  - A case-control study was conducted in Saudi Arabia, where the same strain of BCG
      has been used and surveys had shown that up to 88% of vaccinated children remain
      tuberculin negative. Active cases were obtained by surveying the seven
      tuberculosis centers in 1 yr. Control subjects were obtained from a nationwide
      survey of normal individuals. Vaccination in both groups was ascertained by
      history and BCG scar. Relative risk of contracting active tuberculosis in the
      vaccinated versus unvaccinated and protection was calculated. Protection was as
      follows: age group 5 to 14 yr, 82% (55 to 93%); age group 15 to 24 yr, 67% (55 to
      77%); and age group 25 to 34 yr, 20% (-6 to 37%). We document the uninterrupted
      record of protection by BCG administered in the neonatal period and discuss the
      significance of vaccination timing. We concur with other studies that protection
      lapsed after about 20 yr. More importantly, this is the first large study that
      documents a lack of tuberculin sensitivity despite protection. This challenges
      the view that sensitization is essential for protection and supports the "two
      pathway" theory that BCG vaccination could trigger either protective (Lister
      type) or antagonistic (tuberculin or Koch type) reactions and that the most
      protective vaccines would have little tuberculin-sensitizing effect because the
      two pathways are competitive.

PMID- 7582298
TI  - Priming of alveolar macrophages for interleukin-8 production in patients with
      idiopathic pulmonary fibrosis.
AB  - We evaluated the contribution of interleukin-8 (IL-8) to the pathogenesis of
      idiopathic pulmonary fibrosis (IPF) by studying bronchoalveolar lavage fluid
      (BALF) in eight patients with IPF in the chronically progressive phase, five
      patients with IPF in the subacutely progressive phase, eight patients with
      sarcoidosis (SAR), and eight control (CTL) subjects. IL-8 levels were not
      increased in the BALF of the patients with IPF in the chronic phase (11.3 +/- 8.8
      pg/ml), nor in that of the SAR patients (13.8 +/- 7.8 pg/ml), whereas they were
      increased in the BALF of patients with IPF in the subacutely progressive phase
      (1.93 +/- 1.10 ng/ml). We then investigated extracellular and cell-associated IL
      8 in lipopolysaccharide (LPS)-stimulated BALF cells to determine the IL-8
      producing potential of alveolar macrophages (AM). Following LPS stimulation of
      BALF cells from patients with IPF in the chronic phase, both the extracellular IL
      8 in culture fluid and the cell-associated IL-8 in AM were increased as compared
      with those for the CTL subjects (p < 0.05 and p < 0.05, respectively). These
      results suggest that AM of patients with IPF are primed for IL-8 production. We
      conclude that IL-8 may play a role in neutrophilic alveolitis, especially during
      the subacute phase of IPF.

PMID- 7582300
TI  - Contribution of secretory leukocyte proteinase inhibitor to the antiprotease
      defense system of the peripheral lung: effect of ozone-induced acute
      inflammation.
AB  - Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally
      similar, low-molecular-weight antiproteases produced in the lung. We have
      developed a simple method for distinguishing the antiprotease activities of SLPI
      and elafin in lung lavage fluid from those of alpha 1-antitrypsin (alpha 1-AT)
      that is based on the resistance of the low-molecular-weight antiproteases to
      inactivation by cetyltrimethylammonium bromide. In a study of 23 healthy,
      nonsmoking volunteers, we found that the low-molecular-weight antiproteases
      accounted for 22 +/- 2% (mean +/- SEM, n = 23) of the total neutrophil elastase
      inhibitory capacity of human bronchoalveolar lavage fluid (BALF). Elafin activity
      was below the limit of detection. SLPI activity (as measured by inhibition of
      alpha-chymotrypsin) accounted for 72 +/- 4% (mean +/- SEM, n = 23) of the low
      molecular-weight antiprotease activity in BALF. Measurements of SLPI in the
      lavage fluid samples by enzyme-linked immunosorbent assay (ELISA) agreed closely
      with values obtained by measuring the activity of this inhibitor. The activity of
      the low-molecular-weight antiproteases decreased significantly (p < 0.05), from
      9.0 +/- 0.8 to 7.0 +/- 0.6 pmol of neutrophil elastase inhibited per mL (mean +/-
      SEM, n = 23), following acute ozone exposure.

PMID- 7582294
TI  - Clinical and chest radiographic features of tuberculosis associated with human
      immunodeficiency virus in Zimbabwe.
AB  - In the developing world, the diagnosis of tuberculosis is dependent on clinical
      and radiologic features as culture facilities are not readily available. It has
      been reported that tuberculosis in HIV-positive persons can present with atypical
      clinical and radiographic features. The object of this study was to examine how
      often atypical features occur in HIV-positive compared with HIV-negative persons
      and how these findings correspond to sputum-smear findings. Detailed demographic,
      clinical, and chest radiographic features of tuberculosis were assessed in 202
      HIV-positive adults and 220 HIV-negative patients admitted consecutively. Using
      univariate analysis, several of these features were found to be significantly
      associated with being HIV-positive, but after multiple regression analysis only,
      age group (15 to 42 yr), a negative tuberculin response, intrathoracic
      lymphadenopathy, and lack of cavitation but not sputum-smear status remained
      significant.

PMID- 7582302
TI  - The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric
      oxide.
AB  - We investigated the effect of zaprinast (M&B 22948), a specific cGMP
      phosphodiesterase inhibitor, on pulmonary arteries isolated from lambs with
      persistent pulmonary hypertension following prenatal ligation of the ductus
      arteriosus. Relaxations to sodium nitroprusside, which donates nitric oxide
      inside the smooth muscle cell, were significantly decreased in pulmonary arteries
      from ligated lambs. Pretreatment with 3 x 10(-5) M zaprinast restored them to
      levels close to those observed in untreated arteries from control animals.
      Further studies in intact newborn lambs were then conducted under three
      experimental conditions: (1) NO inhalation at 6 ppm, (2) zaprinast infusion at
      0.05 mg/kg/min, and (3) combination therapy of zaprinast infusion in addition to
      inhaled NO at 6 ppm. Combined therapy with NO and zaprinast decreased the
      pulmonary artery pressure (34.3 +/- 3%) and pulmonary vascular resistance (64 +/-
      7%) and increased pulmonary blood flow (88 +/- 34%) and postductal PaO2 (287 +/-
      34%) to a significantly greater extent than NO alone, zaprinast alone, or the sum
      of these two responses, indicating a true synergistic effect. Zaprinast
      pretreatment also markedly increased the duration of pulmonary vasodilation to
      nitric oxide. There was no effect on systemic blood pressure with the combined
      therapy. We conclude that zaprinast pretreatment significantly enhances the
      effect of sodium nitroprusside on isolated pulmonary arteries, as well the effect
      of inhaled NO at 6 ppm in newborn lambs with persistent pulmonary hypertension.
      We speculate that phosphodiesterase inhibition may increase the response rate to
      NO or allow the use of much lower inhaled concentrations of NO.

PMID- 7582301
TI  - Aminoguanidine selectively decreases cyclic GMP levels produced by inducible
      nitric oxide synthase.
AB  - Overproduction of nitric oxide (NO) following induction of NO synthase in
      vascular smooth muscle by endotoxin and certain cytokines contributes to the
      vasodilation and hyporesponsiveness to vasopressors that characterize the septic
      circulation. Guanosine 3',5'-cyclic monophosphate (cGMP) mediates the effects of
      NO in vascular smooth muscle. Vessels from animals treated with endotoxin have
      elevated cGMP levels compared with control animals. Aminoguanidine has been
      proposed as a selective inhibitor of the inducible form of NO synthase. This
      study compares the effects of aminoguanidine on phenylephrine-induced
      contractions and cGMP levels in thoracic aortic rings from endotoxin treated (20
      mg/kg intraperitoneally) with sham-treated (1 ml saline intraperitoneally) rats.
      Endotoxin-treatment depressed phenylephrine-induced contraction and raised tissue
      levels of cGMP. Aminoguanidine (100 microM and 1 mM) increased phenylephrine
      induced tension and decreased cGMP levels in a dose-dependent manner in intact
      and endothelium-denuded aortas from endotoxin-treated rats but had no effect on
      vessels from sham-treated rats. These findings are consistent with the hypothesis
      that endotoxin treatment causes increased vascular production of endothelium
      independent NO, which is associated with a diminished response to
      vasoconstrictors. Aminoguanidine decreases indices of NO production only after
      endotoxin treatment, providing further evidence that it is a selective inhibitor
      of inducible NO synthase.

PMID- 7582304
TI  - Exertional oxygen of limited benefit in patients with chronic obstructive
      pulmonary disease and mild hypoxemia.
AB  - It is unclear whether short-term benefits from supplemental oxygen translate into
      improved quality of life in patients with severe COPD. In a 12 wk double-blind
      randomized crossover study, we assessed the effects of supplemental air and
      oxygen on exercise performance (step tests and 6 min walking distance [6MWD])
      initially and after two 6 wk periods at home using exertional cylinder air or
      oxygen. We measured quality of life at baseline and after the two 6 wk
      domiciliary periods. The 26 patients (24 males) had a mean age of 73 +/- 6 yr;
      mean FEV1, 0.9 +/- 0.4 L; mean DLCO, 10.6 +/- 2.4 ml/min/mm Hg; mean resting PO2,
      69 +/- 8.5 (range 58 to 82) mm Hg; mean PCO2, 41 +/- 3.3 mm Hg; and mean resting
      SaO2, 94 +/- 2.1 (mean +/- SD). Laboratory tests were performed breathing
      intranasal air or oxygen at 4 L/min, and measurements were made of SaO2 and Borg
      dysnea scores. Supplemental oxygen increased 6MWD and steps by small,
      statistically significant increments acutely at baseline and after 6 and 12 wk,
      without corresponding falls in Borg score. Degree of desaturation at baseline did
      not correlate with increase in 6MWD or steps achieved at baseline or at 6 or 12
      wk, nor with the domiciliary gas used. There was no difference in 6MWD or steps
      achieved while breathing supplemental oxygen after 6 wk of domiciliary oxygen
      compared with domiciliary air. Small improvements in quality of life indices were
      found after domiciliary oxygen, and mastery also improved after domiciliary air.
      There were no differences in quality of life, however, when domiciliary oxygen
      was compared with domiciliary air. Although oxygen supplementation induced small
      acute increments in laboratory exercise performance, such improvements had little
      impact on the patients' daily lives.

PMID- 7582303
TI  - Cognitive function and assessment of lung function in the elderly.
AB  - The feasibility of spirometry or respiratory impedance measurements for assessing
      lung function in the elderly was compared in 208 institutionalized patients with
      various degrees of cognitive function impairment. Respiratory impedance was
      determined by the forced oscillation technique. Cognitive function was assessed
      by the score for the mini-mental state (MMS) examination. Of the 208 patients,
      126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 <
      or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208
      patients, respiratory impedance measurements were possible in 159, whereas in
      only 85 was spirometry possible. The overall difference between the feasibility
      rates for the spirometric and respiratory impedance measurements was highly
      significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility
      rates for the two techniques was higher in the group of subjects with severe
      cognitive impairment than in the groups with mild impairment and no impairment,
      respectively. Among the 84 patients able to complete both tests, significant
      correlations were found between the spirometric and respiratory impedance
      measurements. These results indicate that respiratory impedance measurement seems
      a more useful tool than spirometry for assessing lung function in elderly
      patients whenever cognitive function is impaired.

PMID- 7582305
TI  - Influence of sleep on ventilatory and upper airway response to CO2 in normal
      subjects and patients with COPD.
AB  - In order to investigate the influence of the dynamic changes in upper airway (UA)
      resistance in the pathophysiology of noctural hypoventilation in COPD, we
      compared the ventilatory pattern and UA resistance, measured at baseline and
      during CO2 rebreathing, in nine normal men and 13 patients with COPD.
      Measurements were made during wakefulness and during non-REM sleep during a
      morning nap after a sleep deprivation night. Ventilatory parameters (VE, VT,
      VT/TI) were calculated from flow measurements using a Fleich no. 3
      pneumotachograph connected to a fitting nasal mask. Pharyngeal pressure was
      measured with a low-bias catheter referenced to the mask pressure. Baseline UA
      resistances (supraglottic resistance: SGR) values were similar in the two groups.
      They significantly increased in both groups from wakefulness to sleep.
      Furthermore, VE and VT/TI were higher in patients with COPD than in normal
      subjects during wakefulness and during sleep. The slope of the VE/PETCO2
      relationship was significantly lower in patients with COPD than in normal
      subjects (p = 0.0001), without any significant decrease between wakefulness and
      sleep. SGR systematically decreased during CO2 rebreathing in both groups during
      wakefulness and during sleep. The slope of SGR/PETCO2 relationship was lower in
      patients with COPD than in control subjects during sleep and during wakefulness
      (p = 0.005), whereas the decrease in SGR with increased VE and VT/TI was similar
      in both groups and not influenced by sleep. We conclude that the impediment in UA
      resistance behavior in response to a hypercapnic stimulus in patients with COPD
      is related to the decrease in their ventilatory response.

PMID- 7582306
TI  - Ventilatory post-stimulus potentiation in patients with brain damage.
AB  - In normal humans when a brief hypoxic ventilatory stimulus is terminated abruptly
      by breathing 100% O2, ventilation during hyperoxia gradually declines to baseline
      prehypoxic levels without an undershoot. This has been interpreted as evidence of
      decay of short-term potentiation (STP), a mechanism located in the brainstem and
      not dependent upon higher center inputs. STP decay may be important in preventing
      periodic breathing by damping ventilatory responses to cyclic stimuli. Patients
      with brain damage commonly have periodic breathing that may be caused partly by
      impairment of STP activation. To test this 12 tracheostomized patients with
      severe brain damage (Glasgow score 9.9 +/- 0.6) were studied. Breathing stability
      was estimated by at least 6 h of capnography and from these records apnea index
      (AI, episodes/hour) and cyclic changes of end-tidal CO2 (c-PETCO2, cycles/hour)
      were derived. STP activation was examined by brief exposure to hypoxia (45 s, end
      tidal O2 = 50 mm Hg) followed by hyperoxia. Forty-four hypoxic-hyperoxic runs
      were analyzed and compared with 19 normoxic-hyperoxic trials. At the end of the
      hypoxia ventilation (VI) increased 39.5 +/- 5.8% and PETCO2 decreased 2.7 +/- 0.6
      mm Hg to 91.5 +/- 2.2% of baseline value. When hypoxia was terminated abruptly by
      hyperoxia VI dropped immediately to 63.2 +/- 7.2% of baseline, remaining for 35 s
      significantly lower than the corresponding values acquired during hyperoxia after
      normoxia. After hypoxia, apneas occurred in 19 of 44 hyperoxic runs. There was a
      negative relationship between nadir hyperoxic ventilation after hypoxia and both
      AI and c-PETCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582309
TI  - Lactic acidosis and diaphragmatic function in vitro.
AB  - Diaphragm fatigue occurs during heavy exercise. Acidosis leads to skeletal muscle
      fatigue, yet the diaphragm is not a net producer of either lactic acid or
      hydrogen ions. We tested the hypothesis that hydrogen ion and lactic acid
      concentrations similar to those seen in arterial blood at maximal exercise
      decrease contractility of the in vitro isolated rat diaphragm. Diaphragm strips
      were exposed to a control solution for 15 min and then to one of the following
      treatment solutions: control (C, pH = 7.4) or 10 mM lactic acid buffered to pH
      7.4 (L74), pH 7.2 (L72), pH 7.1 (L71), or pH 6.8 (L68). After 15 min, the force
      frequency relationship of the strip was measured. The strips were then stressed
      with 75 contractions at 25 Hz (250-ms train duration) at the rate of one per
      second and the force-frequency curve was measured after 15 min of recovery. The
      L74, L72, and L71 strips responded similarly to the C strips at all times and
      frequencies. Decrements in force associated with acidosis were only seen in L68.
      Within L68, we found decreases in force at stimulation frequencies < 100 Hz.
      These data suggest that physiologic levels of exogenous hydrogen ions are not a
      primary cause of in vitro diaphragm fatigue.

PMID- 7582307
TI  - Effect of varying inspired oxygen concentration on diaphragm glutathione
      metabolism during loaded breathing.
AB  - Recent studies have suggested that loaded breathing elicits alterations in
      diaphragmatic glutathione levels that may be mediated by free radicals and may
      also be linked to the development of diaphragm fatigue. While free-radical
      generation in a number of pathophysiologic conditions is known to be a function
      of ambient oxygen concentrations, the effect of varying inspired oxygen
      concentration on the diaphragmatic response to loaded breathing (i.e., on
      diaphragm fatigue and glutathione levels) has not been studied. In this study, we
      compared the effect of loaded breathing, continued until respiratory arrest in
      decerebrate rats breathing room air (RA), with the effect of the same load on
      animals breathing 100% oxygen (O2). After arrest, the animals' diaphragms were
      excised, force generation was assessed in vitro, and diaphragmatic levels of
      reduced glutathione (GSH) and oxidized glutathione (GSSG) were determined.
      Similar measurements were made on unloaded control animals. We found both
      similarities and differences in the response to loading in O2- and RA-breathing
      animals. O2-breathing loaded animals had a greater load endurance, lower blood
      pressure at the end of loading, higher carbon dioxide levels, and greater high
      frequency fatigue at the conclusion of loaded trials than did RA-breathing
      animals. The degree of low-frequency fatigue was similar, however, in the O2- and
      RA-breathing loaded groups (i.e, twitch force averaged 7.9 +/- 0.6, 8.4 +/- 0.5,
      3.8 +/- 0.9, and 4.5 +/- 0.8 N/cm2, respectively, in the RA/unloaded,
      O2/unloaded, RA/loaded, and O2/loaded groups, p < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7582308
TI  - Effect of varying load magnitude on diaphragmatic glutathione metabolism during
      loaded breathing.
AB  - Some studies have suggested that protective mechanisms downregulate diaphragm
      activity during loaded breathing so as to prevent respiratory-muscle fatigue.
      Other work has indicated, however, that loading can sometimes elicit significant
      diaphragmatic fatigue, and that the development of fatigue may be related to
      alterations in diaphragmatic glutathione concentrations. One potential
      explanation for these discrepant observations is that the mechanism of
      respiratory failure may vary as a function of load magnitude, and that some loads
      evoke little fatigue whereas others produce substantial fatigue and glutathione
      alterations. The purpose of this study was to examine this issue by determining
      the diaphragmatic fatigue and alterations in glutathione concentrations produced
      by a range of inspiratory resistive loads. Experiments were performed on
      decerebrate rats divided into a control, unloaded group and a group loaded with
      small, medium, and large inspiratory resistive loads that were applied until
      respiratory failure occurred. After respiratory arrest, the animals' diaphragms
      were excised, an in vitro determination was done of diaphragm contractility
      characteristics, and samples of muscle were assayed for GSH (reduced glutathione)
      and GSSG (oxidized glutathione). We found that in vitro diaphragm force
      generation was severely reduced for loaded breathing, and surprisingly, that the
      magnitude of the low-frequency fatigue present was similar in the three loaded
      groups. Reductions in diaphragmatic GSH levels and increases in GSSG levels were
      found in all three loaded groups. Reductions in diaphragmatic GSH levels and
      increases in GSSG levels were found in all three loaded groups, but again, the
      magnitude of these changes were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582311
TI  - Immunohistochemical identification and characterization of smooth muscle-like
      cells in idiopathic pulmonary fibrosis.
AB  - The interstitium of the fibrotic lung possesses a contractile capability that is
      unusual for nonmuscle tissue. An abundance of actin filament-laden cells have
      been demonstrated in animal and human studies of fibrotic lung tissue and have
      frequently been termed myofibroblasts. The origin and significance of these cells
      remain unclear. Proliferation of cells with the capability to contract and
      thereby generate force within the parenchyma is potentially a significant
      contribution to the increased lung elastic recoil of advanced pulmonary fibrosis.
      In the present study, we immunohistochemically examined these intermediate
      phenotypes of filament-laden cells with a focus on those expressing smooth muscle
      associated isoforms of actin. The monoclonal antibody HHF35 was used to study the
      presence and distribution of cells expressing alpha and gamma smooth muscle actin
      in idiopathic pulmonary fibrosis (IPF). Adjacent sections of tissue from open
      lung biopsies of eight patients with IPF were stained with a pentachrome stain
      and with multiple antibodies (HHF35, polyclonal anti-actin, anti-vimentin, anti
      keratin, anti-procollagen I, and anti-von Willebrand Factor VIII) to identify
      specific cell types. In addition, anti-laminin antibody was used to stain
      basement membrane. Many tightly packed, HHF35-reactive cells were found to be
      architecturally dissociated from airways and blood vessels in all eight patients
      with IPF. Some HHF35-reactive bundles were composed of loosely associated cells,
      and single smooth muscle cell types (SMC) were distributed in the fibrotic
      interstitium. Interestingly, some of the SMC were distinctly negative for anti
      laminin and stained atypically with pentachrome. Moreover, some single SMC were
      found to be anti-procollagen type I reactive with double staining
      technique.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582313
TI  - Upper airway and soft tissue anatomy in normal subjects and patients with sleep
      disordered breathing. Significance of the lateral pharyngeal walls.
AB  - The geometry and caliber of the upper airway in apneic patients differs from
      those in normal subjects. The apneic airway is smaller and is narrowed laterally.
      Examination of the soft tissue structures surrounding the upper airway can lead
      to an understanding of these apneic airway dimensional changes. Magnetic
      resonance imaging was utilized to study the upper airway and surrounding soft
      tissue structures in 21 normal subjects, 21 snorer/mild apneic subjects, and 26
      patients with obstructive sleep apnea. The major findings of this investigation
      in the 68 subjects were as follows: (1) minimum airway area was significantly
      smaller in apneic compared with normal subjects and occurred in the retropalatal
      region; (2) airway narrowing in apneic patients was predominantly in the lateral
      dimension; there was no significant difference in the anterior-posterior (AP)
      airway dimension between subject groups; and (3) distance between the rami of the
      mandible was equal between subject groups, and thus the narrowing of the lateral
      dimension was not explained by differences in bony structure; (4) lateral airway
      narrowing was explained predominantly by larger pharyngeal walls in apneic
      patients (the parapharyngeal fat pads were not closer together as one would
      expect if the airway walls were compressed by fat); and (5) fat pad size at the
      level of the minimum airway was not greater in apneic than normal subjects. At
      the minimum airway area, thickness of the lateral pharyngeal muscular walls
      rather than enlargement of the parapharyngeal fat pads was the predominant
      anatomic factor causing airway narrowing in apneic subjects.

PMID- 7582314
TI  - TNF-alpha mRNA expression in diaphragm muscle after endotoxin administration.
AB  - We studied gene expression and production of TNF-alpha in the diaphragm tissue
      and changes of muscle contractile properties after endotoxin injection
      (Escherichia coli, 20 mg/kg) in 88 rats. We assessed the muscle contractile
      properties by force-frequency curves and twitch kinetics using dissected
      diaphragm muscle strips. The peak tensions of force-frequency curves decreased
      from control values (2.15 +/- 0.2 kg/cm2) up to 4 h (0.81 +/- 0.17, p < 0.001),
      and then increased at 6 h (1.36 +/- 0.19, p < 0.05) after endotoxin injection.
      The cytotoxic activity on L929 cells in arterial blood samples maximally
      increased at 2 h (p < 0.001), then decreased to 6 h (p < 0.05). TNF-alpha mRNA in
      diaphragm tissue was detected by Northern blot method at 1 and 1.5 h, and the
      immunolocalization of TNF-alpha was evaluated at 2 and 4 h by
      immunohistochemistry in the muscle tissues. Furthermore, preinjection with anti-m
      TNF-alpha antibody prevented the decrement of force-frequency curves after
      endotoxin injection of 10 microliters/kg. From this evidence that TNF-alpha gene
      expression and production occurred in the diaphragm tissue, but anti-m TNF-alpha
      antibody preinjection prevented the deterioration of diaphragm muscle contractile
      properties, we suggest that TNF-alpha may act on muscle cells extracellularly.

PMID- 7582315
TI  - Effect of bullectomy on diaphragm strength.
AB  - Surgical removal of bullous lesions in selected patients with chronic obstructive
      pulmonary disease may significantly improve lung function, gas exchange, and
      functional status and reduce dyspnea. Proposed mechanisms by which bullectomy may
      produce these beneficial effects include (1) improving ventilation and perfusion
      matching by allowing compressed viable lung to re-expand and participate in gas
      exchange; (2) restoring outward elastic tension on small airways, thereby
      reducing airways obstruction; and (3) reducing end-expiratory lung volume,
      thereby diminishing the adverse effects of chronic hyperinflation on chest wall
      elastic recoil and inspiratory muscle force generation. In this report, we
      demonstrate the effect of bullectomy on transdiaphragmatic pressure generation,
      gas exchange, and exercise capacity in a patient with severe bullous emphysema
      who underwent unilateral bullectomy.

PMID- 7582310
TI  - Endothelin-1 receptor density, distribution, and function in human isolated
      asthmatic airways.
AB  - The potent bronchoconstrictor and mitogenic actions of the peptide endothelin-1
      (ET-1) on airway smooth muscle may contribute significantly to the bronchial
      obstruction observed in asthma. However, the status of the receptor-effector
      systems that mediate these actions of ET-1 in asthmatic airways is currently
      unknown. Thus, we have used quantitative autoradiographic and isometric-tension
      recording techniques to evaluate the density, distribution, and function of the
      specific receptors that mediate the actions of ET-1 in both asthmatic and
      nonasthmatic airways. Here, we report that similar numbers of specific binding
      sites for [125I]-ET-1 exist in asthmatic and nonasthmatic airways, with the
      greatest densities located in airway smooth muscle in both tissue types. The ETB
      receptor subtype constituted approximately 82% and 88% of these receptors for ET
      1 in asthmatic and nonasthmatic human bronchial smooth muscle, respectively, and
      mediated contraction in response to this peptide. In addition, a component of ET
      1-induced contraction appeared to be mediated by a non-ETB, BQ-123-resistant
      mechanism. Furthermore, a small population of ETA sites was identified that did
      not mediate contraction, but which may have a role in ET-1-induced prostanoid
      release and airway smooth-muscle proliferation. Interestingly, bronchial smooth
      muscle from asthmatic lung was significantly less sensitive to the contractile
      effects of ETB receptor activation, consistent with desensitization of this
      receptor subtype in response to the increased production and release of ET-1 that
      occurs in this disease.

PMID- 7582316
TI  - Laboratory contamination of Mycobacterium tuberculosis cultures.
AB  - The purpose of this study was to investigate possible laboratory contamination of
      Mycobacterium tuberculosis cultures which resulted in the misdiagnosis of
      tuberculosis. We have investigated three cases in which a patient's culture was
      positive for M. tuberculosis but there was not a high clinical suspicion for
      disease. In each instance, another patient with clinically obvious pulmonary
      tuberculosis had specimens cultured concurrently within the same clinical
      laboratory. The isolates from both the obvious cases of tuberculosis and the
      suspect cases were obtained through the State of Alabama TB Laboratory, but these
      isolates originated at a commercial laboratory, a community hospital laboratory,
      and at a university hospital. MTB isolates were fingerprinted by probing for the
      insertion sequence IS6110. With each of the three pairs of isolates (case and
      suspicious case), identical IS6110 banding patterns were found suggesting
      identical MTB strains. Because the patients were geographically separated, it is
      strongly suspected that laboratory contamination of M. tuberculosis cultures
      resulted in the three suspect cases being diagnosed with tuberculosis. These
      findings indicate that positive M. tuberculosis cultures resulting from
      laboratory contamination can occur.

PMID- 7582317
TI  - Aging and hepatotoxicity of isoniazid and rifampin in pulmonary tuberculosis.
AB  - We evaluated whether elderly patients with pulmonary tuberculosis and without
      apparent preexisting liver disease are at an increased risk to develop
      hepatotoxicity from an isoniazid-rifampin regimen and require regular liver
      function tests in comparison with younger patients. We analyzed the data of 131
      patients treated in the period 1980-1985 of whom 64 (49%) were at least 60 yr of
      age. Subsequent increases of transaminases (measured weekly for as long as 4 wk
      after the start of treatment and later on when symptoms suggestive of
      hepatotoxicity occurred) above baseline values were found more frequently in the
      elderly (38 versus 18%, p < 0.05) and were also more pronounced in them (p <
      0.01). The ratio of the highest transaminase value over the baseline value was
      called the transaminase index (TI). A TI of at least 5 was found in 22% of
      elderly and 8% of younger patients (p = NS), but ratios as high as 10 were mostly
      asymptomatic and always normalized progressively without treatment adjustment.
      Only symptomatic patients with a TI > or = 10 (five elderly and three younger)
      required temporary or definitive treatment adjustment. We conclude that repeated
      liver function test evaluations are generally unnecessary, except for symptomatic
      elderly and younger patients alike, in order to detect those with a TI > or = 10,
      thus requiring drug adjustment.

PMID- 7582319
TI  - Future directions for research on diseases of the lung. American Thoracic
      Society. Medical Section of the American Lung Association. This report was
      approved by the ATS Board of Directors in November 1994.

PMID- 7582318
TI  - Rigid external resistances cause effort dependent maximal expiratory and
      inspiratory flows.
AB  - A fixed orifice or a fixed upper airway obstruction (UAO) causes an expiratory
      and inspiratory plateau-shaped limitation on maximal flow-volume (MEFV, MIFV)
      curves and, according to the classic concept, a MEF50/MIF50 ratio of 0.9-1.1.
      However, since maximal expiratory static transrespiratory pressures (PEmax,stat)
      are clearly greater than the inspiratory ones (PImax,stat), the pressures applied
      during forced expiration also must be expected to be greater than inspiratory
      pressures; therefore, the MEF should be larger than the MIF because orifice flow
      is effort-dependent. We investigated this hypothesis in seven healthy, nonsmoking
      male volunteers (mean age +/- 1 SD: 34 +/- 10 yr, FVC: 5.9 +/- 1.0 L, PEmax,stat:
      168 +/- 16 cm H2O, PImax,stat: 107 +/- 33 cm H2O). They performed MEFV curves and
      MIFV curves through four different added resistances placed in between the
      pneumotachograph and the mouth (the orifice diameters ranged between 7.8 mm and
      2.8 mm). During these maneuvers dynamic mouth pressures were also measured (PE
      and PI). We found that the MEF50/MIF50 ratios were significantly increased (p <
      0.05) from a control value of 1.1 +/- 0.4 up to 1.5 +/- 0.3 with the resistances.
      For each added resistance the PE/MEF ratios and (-)PI/MIF ratios were situated on
      a single line corresponding with the pressure-flow (P/V) characteristics of the
      resistance. We concluded that external resistances cause a MEF50/MIF50 ratio of
      clearly more than 1 and that this is determined by the PE/(-)PI ratio, which in
      healthy subjects is markedly larger than 1.

PMID- 7582312
TI  - Alveolar inflammation and its relation to emphysema in smokers.
AB  - The prevalent theory in the pathogenesis of emphysema proposes that increased
      numbers of activated neutrophils and/or alveolar macrophages produce large
      amounts of proteases, an activity that cannot be regulated by alpha 1
      antiproteases, resulting in lung destruction. However, the cells in the lung
      parenchyma of smokers have not been properly identified. We characterized and
      quantitated the inflammatory cell load in the lungs of smokers and correlated
      these findings with the degree of lung destruction. Twenty-one patients, six
      nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes
      were fixed and stained for light microscopy and neutrophil identification and
      immunohistochemically stained for identification of lymphocytes and macrophages.
      By point counting, we determined the extent of emphysema by the volume density of
      the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter
      in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of
      neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01),
      whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = 
      0.78) correlated negatively with the Vvalv. The number of T-lymphocytes
      correlated negatively with the number of neutrophils (r = -0.58) and positively
      with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as
      long as the inflammatory reaction is predominantly of neutrophils there is no
      destruction of the lung. However, the extent of lung destruction becomes evident,
      and its extent is directly related to the number of alveolar macrophages and T
      lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly
      implicated in the pathogenesis of emphysema in smokers.

PMID- 7582320
TI  - Normal sweat chloride values do not exclude the diagnosis of cystic fibrosis.

PMID- 7582321
TI  - Is allergen immunotherapy effective in asthma? A meta-analysis of randomized
      clinical trials.

PMID- 7582322
TI  - Standards for the diagnosis and care of patients with chronic obstructive
      pulmonary disease. American Thoracic Society.

PMID- 7582323
TI  - A transputer-based physiological signal processing system. Part 1--System design.
AB  - This paper, the first of two, details the design and in-vitro testing of a
      transputer-based physiological signal processing system. The heart of the system
      is a transputer-based digital signal processing (DSP) board which can act as a
      stand-alone spectrum analyser, designed to operate in the audio-frequency band up
      to 25 kHz. The board comprises a T800 processor, two A100 transversal filters, 12
      bit A-D circuitry capable of sampling up to 48 kHz, memory and address mapper.
      The initial application of the system is for the detection of early arterial
      disease. For this the DSP board is harnessed to the front end of a multigate
      pulsed Doppler ultrasound scanner operating at 4.8 MHz insonation frequency and
      incorporating a vessel wall tracking unit. The complete system performs a Fourier
      transform on the backscattered signals, providing spectral information on
      discrete areas of flow (0.6 mm3) across the vessel lumen in real time. This first
      paper describes the hardware, and the second describes the performance testing of
      the system on the bench and an assessment of its ability to detect low grade
      stenoses during steady flow.

PMID- 7582324
TI  - Two miniature monitors for long-term ambulatory studies.
AB  - Two very low-power monitors are described. One typically limb-worn to record the
      level of physical activity of a person; the other, used with surface electrodes,
      to record three parameters of an EMG signal. The monitoring period can extend to
      days with a very accurate 'time of event' log. A novel method has been devised to
      double the resolution of the data gathered. A PC is used to store and process the
      collected data, which can be displayed or printed as one-, or four-channel, time
      related histogram. The gathered data can also be analysed for trends and other
      statistical analysis. The hardware is relatively simple and made from low-cost
      components. Neither monitor uses a microprocessor for data gathering. The system
      is very easy to use requiring minimal operator training. Where 'no-frills'
      ambulatory monitoring is called for, the systems presented would compare very
      favourably with other commercially available monitors, either on cost, complexity
      of setting up, or on weight.

PMID- 7582325
TI  - Effect of interference on the performance of glucose enzyme electrodes using
      Nafion coatings.
AB  - The negatively charged perfluorinated ionomer Nafion was used as a coating on
      hydrogen peroxide detecting platinum electrode as well as on a polycarbonate
      diffusion membrane in the construction of a glucose amperometric enzyme
      electrode. The current response of these electrodes to hydrogen peroxide,
      ascorbic acid, acetaminophen, uric acid and glucose was studied and the coating
      procedure was optimized. It was confirmed that the Nafion coating prevents
      interference by anionic substances such as ascorbic acid and uric acid, and
      decreases acetaminophen interference. In this regard it was shown that coating
      the glucose diffusion membrane (polycarbonate) was more effective than coating
      the platinum wire itself, because of the prevention of the homogeneous redox
      reaction of the interference species with hydrogen peroxide, as well as the
      additional diffusional resistance to the glucose flux. The glucose levels in
      serum samples were estimated and the stability of the enzyme electrodes during
      continuous operation in serum was studied. An enzyme electrode with constant
      sensitivity of ca. 1 microA/mM and a linear range of up to 15 mM, unaffected by
      contact with serum, is reported.

PMID- 7582326
TI  - Construction of a morphological filter for detecting an event-related potential
      P300 in single sweep EEG record in children.
AB  - A morphological filter for single sweep records of event-related potential (ERP)
      obtained in an auditory oddball paradigm, especially P300 waveform, was
      constructed. By combining four basic operations; erosion, dilation, opening and
      closing, we could derive a desired filter whose properties fit the current
      objectives. The morphological filter for the single sweep records of ERP was
      constructed by taking into account the features of the signal and noise
      components. The morphological filter had superior properties for distinguishing
      the signal from the noise even when both were within the same frequency band, as
      in case of children. The constructed morphological filter was evaluated by using
      the simulation data of ERP and then applied to the actual ERP data obtained from
      nine normal children. The constructed morphological filter was proved to be an
      appropriate tool for single sweep analysis of ERP.

PMID- 7582327
TI  - A radial basis function model of muscle stimulated with irregular inter-pulse
      intervals.
AB  - Paralysed muscle, or skeletal muscle which is to be used for cardiac assistance,
      may be given an artificial function if it is electrically stimulated to contract
      and the response can be adequately controlled. To design a controller, a model of
      the muscle or system is usually required. The most commonly used models are
      analogues, originating from A.V. Hill's model. However muscles exhibit many
      nonlinear and time-varying phenomena which, if they are to be modelled, make the
      analogue complex and cumbrous to work with. The system may further be complicated
      by pathological changes and secondary effects of stimulation. We propose that
      such a system can be modelled by nonlinear networks ('neural networks'). The
      radial basis function network (RBF) has two advantages over the better-known
      multi-layer perceptron (MLP). We describe the use of an RBF network to model
      rabbit muscle that is supramaximally stimulated at irregular inter-pulse
      intervals.

PMID- 7582328
TI  - A high-resolution large array (HRLA) surface EMG system.
AB  - A high-resolution large-array (HRLA) SEMG system comprising 256 separate channels
      has been developed. SEMG signals are detected by a "bracelet" active electrode
      array connected to a stack of newly designed biopotential instrumentation
      amplifiers. A stand-alone data logger acquires and stores the array EMG activity
      at high sampling rates. A RISC multiprocessor network supports computationally
      intensive array signal processing and analysis algorithms. In addition, an
      improved optoelectronic system for the measurement of human body kinematics has
      been associated to the HRLA SEMG system to provide the related mechanical
      characteristics of muscle activity. Analysis results demonstrate that high
      resolution muscle fibre conduction velocity histograms can be obtained even from
      skeletal muscles in which a large number of motor units are simultaneously
      activated.

PMID- 7582329
TI  - Running discrete Fourier transform for time--frequency analysis of biomedical
      signals.
AB  - The present work introduces a running discrete Fourier transform (RDFT) for time
      frequency analysis (TFA) of nonstationary short-term signals. The RDFT algorithm
      adapts a window function, which has adjustable time-frequency characteristics. A
      generalized weighting filter was proposed, which maps the time-dependent signal
      into the time-frequency plane. As an example the weighting filters were deduced
      for exponential, gamma and binomial window sequences. Application of the RDFT
      algorithm to the analysis of biomedical signals is discussed.

PMID- 7582330
TI  - Remote measurement of small displacements using a CD pickup head.

PMID- 7582331
TI  - A model for peak expiratory flow allowing for back pressure and distensibility.
AB  - A mathematical model has been constructed which relates measured peak flow to
      identifiable individual characteristics of peak flow meters and patients. It
      gives qualitatively correct results, but requires further clinical data for the
      effects of pressure on respiratory tract volume. It is capable of reconciling
      calibrations of peak flow meters and thus is of utility in investigation of the
      underlying reasons for variations in peak flow capabilities of patients.

PMID- 7582334
TI  - Critique of AHCPR's consumer guide--"treating pressure sores".
AB  - The consumer version of the clinical practice guidelines entitled "Treating
      Pressure Sores" was released by the Agency for Health Care Policy and Research
      (AHCPR) in December 1994. This review of the patient teaching booklet compares it
      to existing criteria-evaluating written tools. The AHCPR 1994 Consumer Guide
      meets almost all the criteria; one area that still needs improvement is the
      reading level.

PMID- 7582333
TI  - Metrological opportunities of the dynamic mode of operating an enzyme
      amperometric biosensor.
AB  - An algorithm for generating calibration curves that reflects the peculiarities of
      the dynamic mode of operating of the amperometric biosensor, created on the base
      of numerical simulations of the sensor behaviour, is proposed. The most important
      steps are: selection of the informative quantity about the sensor current versus
      time relationship and the calibration curve processing. Five different
      informative quantities are tested as well as two ways of representation of
      calibration curves. The object of study is enzyme catalyzed selective reaction.
      The values of the kinetic constants used reflect the conversion of glucose to
      gluconolacton catalyzed by glucose oxidase (GOD) and catalase (CAT). The results
      show that sensors with different metrological characteristics can be created by
      means of a selection of informative quantity of the signal of one biosensor
      transducer. In addition there appears to be a possibility of facilitating the
      calibration procedure and prolonging the life of the biosensor.

PMID- 7582332
TI  - Slip sensors for the control of the grasp in functional neuromuscular
      stimulation.
AB  - In this paper we present the results of research on the role of slip and force
      sensors in the control of grasp by means of functional neuromuscular stimulation
      (FNS) when applied to plegic subjects. From our study, it emerged that a reliable
      control strategy can be more efficiently based on the slip signal than on the
      signal related to the force exerted by the fingers. A prototype system involving
      both slip detectors, realized by means, of inductive transducers, and force
      sensors has been designed.

PMID- 7582335
TI  - Latex allergy anaphylaxis in a spina bifida patient with a pressure ulcer.
AB  - At a Memphis, Tenn., children's hospital, latex-free surgery is mandated for
      patients with spina bifida or for those who have had multiple surgeries to
      correct congenital urinary anomalies. Even in the absence of a positive clinical
      history, both categories of patients are presumed to have a latex allergy or
      sensitivity. This case report illustrates the severe anaphylactic reaction that
      may occur with exposure to latex gloves or glove powder that transfers the
      antigen. The increasing incidence of latex rubber allergy for patients and health
      care workers is reviewed. Screening for patients at risk for allergy is outlined.
      These allergic patients can undergo safe operations if precautions are undertaken
      to avoid latex exposure. Precautions must also be initiated and enforced
      throughout the hospital for treatment of the patient in the pre- and post
      operative period.

PMID- 7582338
TI  - Leg ulcer treatment: providing effective care in the community.
AB  - The cost effectiveness of two different hydrocolloid dressings for healing venous
      ulcers in patients being cared for in the community in the United Kingdom is
      described. The importance of defining performance indicators against which
      treatment can be measured is emphasized.

PMID- 7582337
TI  - Leg ulcer treatment in hospital and primary care in Sweden: cost-effective care
      and quality of life.
AB  - Because of significant reductions in the Swedish health care budget, the trend in
      the Swedish health care service is to move patients with leg ulcers out of
      hospitals and into primary care or community home care. This study compares the
      costs for a 6-week treatment of patients with leg ulcers in primary care.
      Subjects were randomly assigned to one of the two treatment groups--wet-to-dry
      saline gauze dressings changed twice a day or a hydrocolloid dressing (HCD)
      DuoDERM changed when needed or once a week. A variety of costs, including travel
      costs for the nurses, time for dressing changes, and material (including
      ancillary items) were compared.

PMID- 7582336
TI  - Cost-effective wound care: new priorities driven by outcomes.
AB  - International demands for optimizing the quality and cost effectiveness of health
      care requires the rethinking of traditional wound care paradigms. This essay
      defines cost effectiveness as the comparative measure of costs to achieve a given
      clinical outcome. Among some of the issues that need to be addressed are having
      more studies that compare the cost effectiveness of wound care modalities,
      defining what an acceptable outcome for a prescribed treatment program is,
      deciding who should define the significant outcome, and measuring the values of
      each therapy.

PMID- 7582339
TI  - Nursing and medical care of pressure ulcers in hospitals in France.
AB  - The prevalence of pressure ulcers in hospitals in France is given, and the
      anatomical location of these ulcers is explored. The importance of establishing
      accurate stages for these wounds is also emphasized. Four methods of cost
      effectiveness analysis are proposed and described: analysis of one case; analysis
      of one ward; analysis of care time; and analysis of one tetraplegic young man.

PMID- 7582341
TI  - Cost effectiveness of pressure ulcer care in the United States.
AB  - The United States has seen an increase in management of pressure ulcers in
      extended care. The experiences of an expert wound care nurse providing
      consultation in an extended care facility are described. As a result of this
      consultation and implementation of protocols, pressure ulcer prevalence rate
      decreased from 12% to 4%.

PMID- 7582342
TI  - Comments on support surfaces in AHCPR Guidelines.

PMID- 7582340
TI  - Infection and the impact on cost effectiveness in wound care.
AB  - The financial impact of infections in treating persons with traumatic injuries at
      a hospital in Johannesburg, South Africa, are described. Principals of the
      management of infected wounds are reviewed. Factors that influence the choice of
      reconstructive options are given. The cost of using various dressings,
      particularly occlusive dressings, in the management of infected wounds is
      explored. This real problem in the wound care discipline commands due respect,
      and the literature is testimony to this. Central to the management of this
      potential complication in surgery is the oft-cited question of which prophylactic
      antibiotic to administer. The issue is so important in fields such as
      cardiothoracic surgery, hip joint replacement, and intracranial surgery, that the
      thought of not administering prophylactic antibiotics is not entertained.

PMID- 7582343
TI  - Managing pressure ulcers.

PMID- 7582344
TI  - [Determination of nursing tarifs according to performance].

PMID- 7582347
TI  - [Educational offensive by nursing federations].

PMID- 7582346
TI  - [Where to put Mother?].

PMID- 7582348
TI  - [Wrong handling costs money and hurts the environment].

PMID- 7582349
TI  - [New concepts in the care of the elderly. "Hello, here we are, and we are
      alive!"].

PMID- 7582350
TI  - [Prevention of oral candidiasis and parotitis. The importance of oral hygiene is
      often underrated].

PMID- 7582345
TI  - [The Isny declaration. October 17, 1994].

PMID- 7582351
TI  - [Humane death in the hospital. "It was quite lively there"].

PMID- 7582353
TI  - [Gene technique--what is it?].

PMID- 7582356
TI  - [Personnel development in nursing. Inservice training has an effect on the
      activities of nursing administration].

PMID- 7582354
TI  - [Quality assurance and management in the nursing service. Does the quality of
      patient transfer have an effect on hospital economics?].

PMID- 7582355
TI  - [Nursing education in the Seychelles. Between coconuts and bananas].

PMID- 7582352
TI  - [Dying in the hospital. 1. Exclusion of the concept of death in hospital care].

PMID- 7582358
TI  - [The topic of dementia in teaching: the aim is self-activation].

PMID- 7582357
TI  - [Delegating physicians' measures to the nursing staff: uncertainty about the
      legal status in the giving of injections].

PMID- 7582359
TI  - Where does high-resolution computed tomography fit into the investigation of
      diffuse lung disease?

PMID- 7582360
TI  - CSAG report: standards of care for people with diabetes.

PMID- 7582361
TI  - Recent advances in the diagnosis and treatment of acute appendicitis.
AB  - Unnecessary appendicectomy carries long-term risks to the patient. The decision
      for surgical intervention is often made based on the patient's history and the
      findings of clinical examination. This article reviews recent papers published on
      the various methods of reducing the incorrect diagnosis of acute appendicitis,
      and the advances in its treatment.

PMID- 7582362
TI  - Gut-derived mediators of multiple organ failure: platelet-activating factor and
      interleukin-6.
AB  - Laboratory studies suggest that the postischaemic gut serves as a priming bed for
      circulating neutrophils that provoke multiple organ failure. Platelet-activating
      factor, generated by phospholipase A2, appears to be active in priming
      neutrophils in the gut. Interleukin-6 also appears to be elaborated by the
      postischaemic gut, but may be even more important in distant organs via promoting
      neutrophil-mediated organ dysfunction.

PMID- 7582363
TI  - Fast-tracking in cardiac surgery.
AB  - Fast-tracking in cardiac surgery evolved as the pressure on bed space in
      intensive therapy units (ITU) grew and clinical management improved. It relies on
      achieving a patient condition that allows for earlier extubation and
      postoperative management in alternative facilities to the ITU.

PMID- 7582364
TI  - Dyslipidaemia and coronary heart disease: nature vs nurture.
AB  - In order to enhance health care for patients with coronary heart disease (CHD),
      genetic markers of susceptibility could be incorporated into a formula for risk
      evaluation that includes traditional factors. Preventive measures could then be
      targeted towards 'high-risk' subjects. But can the genetic component be dissected
      from the environmental component in an intermediate CHD phenotype, such as plasma
      lipoproteins.

PMID- 7582365
TI  - Decision-making in surgery: splenectomy.
AB  - Interest in splenectomy is topical because of the need to develop protocols for
      the prevention of overwhelming systemic infections postsplenectomy. Partial
      splenectomy is possible in only a few patients undergoing splenectomy for trauma.
      In haematological disorders, total splenectomy is mandatory. All patients who
      have had a total splenectomy will require vaccination and antibiotic prophylaxis.

PMID- 7582366
TI  - Outpatient endometrial assessment.
AB  - Over the past 10 years, outpatient endometrial assessment has largely replaced
      traditional dilatation and curettage, offering a quick, reliable and cost
      effective alternative which avoids the need for general anaesthesia. The
      techniques available and their scope are discussed in detail.

PMID- 7582367
TI  - Help available for parents of disabled children.

PMID- 7582368
TI  - The use of colloids in clinical practice.
AB  - The use of colloid solutions for fluid resuscitation in hypovolaemic patients is
      widespread in clinical practice. This article describes the types of colloid
      agents which are currently available, their physicochemical properties, and
      adverse effects which may follow their administration. The relative merits of
      colloids compared with crystalloid solutions are discussed.

PMID- 7582370
TI  - Phantom pancreatic tumours.

PMID- 7582371
TI  - Doctors as managers: juniors and seniors.
AB  - Doctors have been encouraged to take an active part in management for a numbers
      of years. So, where are we now? What about the doctors/managers of the future?
      What happens next?

PMID- 7582369
TI  - Emergency and long-term management of bleeding oesophageal varices.

PMID- 7582372
TI  - Section 9 police statement and junior doctors.

PMID- 7582374
TI  - Entamoeba histolytica and Giardia lamblia infections: current diagnostic
      strategies.
AB  - Entamoeba histolytica and Giardia lamblia constitute, in a world context, the two
      commonest intestinal protozoan parasites to affect man. Therefore accurate
      diagnosis is of paramount importance if resultant infections are to be adequately
      managed. Demonstration of the cyst or trophozoite stage in a faecal sample(s)
      (several newer techniques are available) remains the lynch-pin of diagnostic
      strategies; however, excretion of cysts, especially, is intermittent and evidence
      of infection is not always manifest in a single examination. A limited range of
      other techniques is also available for a 'parasitological diagnosis'. Within the
      last decade, serological techniques (largely dependent on invasive properties of
      the organism) have attained levels of diagnostic competence. Therefore, a very
      high index of suspicion now ensues from indirect evidence of infection.

PMID- 7582373
TI  - Treacher Collins syndrome.

PMID- 7582376
TI  - Specific diagnostic antigens of Echinococcus granulosus detected by western blot.
AB  - A western blot assay was performed for the detection of Echinococcus granulosus
      specific antigens useful for the diagnostic of hydatic disease. 191 sera were
      tested, 105 coming from patients with different localizations of hydatic cysts
      and 86 from persons either healthy or presenting other diseases. 48 different
      antigenic bands were detected using sera from patients with hydatidosis. A 35 kDa
      antigen co-migrating with a band labeled by a McAb specific of antigen 5 was
      recognized in western blot by only 68% of the sera able to precipitate antigen 5
      in immunoelectrophoresis. A 8 kDa antigen corresponding to the specific E.
      granulosus antigen already described has been recognized by 80% of the sera
      coming from patients with hydatidosis and not by the 86 control sera. Bands of
      21, 30, and 92 kDa appeared also specific and were recognized by at least 50% of
      tested sera. These antigens appeared unrelated one to each other. 103 out of the
      105 sera from patients with hydatidosis were able to recognize at least one of
      the 8, 21, 30, 35 or 92 kDa specific antigens. The present results suggest that
      western blot could be useful for the diagnosis of hydatidosis as far as the
      criteria of positivity is based on the recognition of at least one of the major
      specific antigens.

PMID- 7582375
TI  - Covalent cross-linking of liver collagen by pyridinoline increases in the course
      of experimental alveolar echinococcosis.
AB  - We report that covalent cross-linking of collagen molecules by pyridinoline
      increases significantly in liver in a murine model of alveolar echinococcosis.
      The highest amount of pyridinoline per collagen molecule (up to 3.5 fold the
      control values) is found in liver parasitic lesions. It is also increased, but to
      a far lesser extent, at distance from the fibrotic areas, in macroscopically
      normal zones of the liver, suggesting that the increase in mature collagen cross
      linking occurring in the fibrogenesis due to Echinococcus multilocularis
      infection involves the whole liver. The comparison of these data with those we
      have obtained in another parasitic disease, murine schistosomiasis leading to a
      milder liver fibrosis, largely reversible following chemotherapy, supports a
      relationship between the liver pyridinoline level and the severity of liver
      fibrosis. Pyridinoline could be a tissular marker of chronic liver fibrosis in
      parasitic diseases.

PMID- 7582377
TI  - A new zoonosis of the cerebrospinal fluid of man probably caused by Meningonema
      peruzzii, a filaria of the central nervous system of Cercopithecidae.
AB  - A female fourth stage larva of Meningonema, probably of M. peruzzii Orihel et
      Esslinger, 1973, was recovered in Cameroon, from the cerebrospinal fluid of a
      patient harbouring Loa loa, but without any neurological signs. This observation
      is the first human case of Meningonema (Filarioidea Splendidofilariinae) which
      usually parasitizes the central nervous system of African Cercopithecinae.
      However, as indicated by Orihel and Esslinger, it seems probable that the
      perstans-like microfilariae described in cases of cerebral filariasis in Zimbabwe
      belonged to the same species.

PMID- 7582379
TI  - Circulation in the lymphatic system and latency of Plasmodium merozoites.
      Preliminary note.

PMID- 7582378
TI  - Detection of Toxoplasma gondii parasitemia by polymerase chain reaction in
      perorally infected mice.
AB  - Sequential blood samples collected from mice infected perorally with an avirulent
      strain of T. gondii were analysed for parasite DNA by a polymerase chain reaction
      method (PCR). Two pairs of primers specific for gene B1 and the repetitive DNA
      sequence TGR1E were used for DNA amplification. Amplified products were detected
      by means of electrophoresis with ethidium bromide staining. Parasitemia was also
      determined by cell culture. Parasitemia was never detected by the tissue culture
      method, whereas parasite DNA was continuously detected with PCR from day 2 to day
      21. These results confirm the high sensitivity of PCR for T. gondii DNA in blood,
      and show that circulating DNA is present for long periods in mice following
      primary infection.

PMID- 7582380
TI  - Lacking effect of grapefruit juice on theophylline pharmacokinetics.
AB  - Grapefruit juice inhibits the biotransformation of several drugs, including
      caffeine (23% clearance reduction), which is metabolized by the cytochrome P450
      isoform CYP1A2. Since CYP1A2 also participates in theophylline biotransformation,
      a randomized change-over study on a possible interaction between grapefruit juice
      and theophylline was conducted. Twelve healthy young male nonsmokers were
      included (median 26 (range 23-30) years, weight 73 (65-85) kg). Theophylline was
      given as a single dose of 200 mg in solution (Euphyllin 200), diluted by 100 ml
      of either water or grapefruit juice (751 mg/l naringin). Subsequently, additional
      fractionated 0.91 of water or juice were administered until 16 hours postdose.
      Theophylline concentrations in plasma withdrawn up to 24 hours postdose were
      measured by HPLC, and its pharmacokinetics were estimated using compartment model
      independent methods. To compare between the 2 treatments, ANOVA based point
      estimates and 90% confidence intervals (given in parentheses) were calculated for
      the test (= grapefruit coadministration) to reference (= water coadministration)
      ratios (Tmax: differences). These were: Cmax 0.90 (0.81-1.00), AUC 1.02 (0.95
      1.11), Cmax/AUC 0.88 (0.81-0.95), T 1/2el 1.03 (0.98-1.09), Tmax 0.15 h (-0.11h
      0.41 h). Thus, no pharmacokinetic interaction between grapefruit juice and
      theophylline was observed. This finding is in contrast to the effect of
      grapefruit juice reported on caffeine metabolism and may be due to the
      contribution of enzymes other than CYP1A2 to primary theophylline metabolism or
      to differences in naringin and/or naringenin kinetics between studies.

PMID- 7582382
TI  - A simple analysis of crossover studies with one-group interaction.
AB  - The crossover trial has an intuitive appeal to clinicians because each patient is
      use as his own control. Thus, between-subject variability of symptoms is
      eliminated. However, this study design suffers frequently from the bias of
      treatment-by-period interaction. If, for example, the effect of the first
      treatment period carries on into the next one, then it influences the response to
      the later period (carryover effect). A second problem is that the standard
      approach (Hills-Armitage analysis) for interaction has little power. This led the
      FDA and some statisticians to discourage the use of crossovers. In the present
      report I take issue with the common clinical situation where there is carryover
      effect in only one of the groups of a trial and present a simplified analysis for
      this situation with more power than the standard analysis.

PMID- 7582381
TI  - The impact of long-term cyclosporin-A therapy on hematological and biochemical
      profile in renal transplant patients.
AB  - With over a decade of extensive clinical use of cyclosporin A (CsA), assessment
      of its long-term safety implications is due. In this study the impact of long
      term continuous use of CsA on a number of hematological and biochemical
      parameters in renal transplant patients was evaluated. Two groups of 13 patients
      each, one on conventional therapy (azathioprine + prednisolone) and the other on
      triple therapy (azathioprine + prednisolone + CsA) for 4 to 15 years post
      transplantation were compared with respect to their current and overall
      laboratory values and clinical outcome. Laboratory values were also compared with
      those of 23 matched healthy subjects. No significant difference in the clinical
      outcome was found between conventional and triple therapy groups, however, the
      triple therapy group had significantly less favorable mean values compared to the
      conventional therapy group with respect to hemoglobin (12.1 +/- 2.2 vs 13.3 +/-
      2.1 g/dl, p < 0.02), hematocrit (0.36 +/- 0.06 vs 0.42 +/- 0.03 l/l, p < 0.05),
      urea (13.0 +/- 3.7 vs 6.7 +/- 4.3 mmol/l, p < 0.01) and uric acid (460.0 +/- 112
      vs 330 +/- 88 mumol/l, p < 0.05). The increase in serum uric acid levels in the
      triple therapy group was progressive throughout the post-transplant period. For
      the 19 other parameters measured corresponding mean values in the 2 groups were
      comparable. Mean laboratory values for many parameters in both groups, however,
      still differed from those in the control group. These results showed that kidney
      transplant patients on long-term triple therapy have more hematological and
      biochemical abnormalities and no better clinical outcome than those on
      conventional therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582383
TI  - Comparison of the bioavailability and pharmacokinetics of oral methylergometrine
      in men and women.
AB  - OBJECTIVE: To assess and compare the pharmacokinetics and bioavailability of
      methylergometrine (ME) in men and non-pregnant women. DESIGN: A cross-over design
      was used for an oral dose of 0.125 mg and an intravenous dose of 0.200 mg of ME
      in 6 men and 6 non-pregnant women (parallel-design in gender). RESULTS: After
      intravenous administration, the pharmacokinetic profile of ME was described with
      a 2-compartment model. The distribution half-life (t1/2 alpha) in men was 0.19 +/
      0.27 h, in women 0.10 +/- 0.04 h, the elimination half-life (t1/2 beta) 1.85 +/-
      0.28 h, respectively, 1.94 +/- 0.34 h and the total body clearance (CL) 33.2 +/-
      11.8 l.h-1, and, respectively, 22.18 +/- 3.10 l.h-1. For these intrinsic
      pharmacokinetic parameters differences between men and women were not
      statistically significant. After oral administration, the pharmacokinetic profile
      was described with a 1-compartment model. The lag time was subject dependent and
      was significantly longer in men 0.33 +/- 0.09 h than in women 0.09 +/- 0.07 h.
      T1/2 beta in men was 2.08 +/- 0.43 h and was longer than in women 1.42 +/- 0.31 h
      (p = 0.012). In both men and women a large variation of bioavailability was shown
      ranging between 22% and 138%. CONCLUSION: This study with oral methylergometrine
      showed a comparable large interindividual variability in bioavailability in both
      men and women.

PMID- 7582385
TI  - Pharmacokinetics of cetirizine in 2- to 6-year-old children.
AB  - Eight children (3.84 +/- 1.17 years old) received a single oral 5 mg cetirizine
      dose (0.32 +/- 0.07 mg.kg-1) as a 10 mg.ml-1 solution, 1.73 (+/- 0.64) hours
      before a minor surgical intervention (mean duration +/- SD = 0.90 +/- 0.25 h).
      Seven venous blood samples were collected before administration (t0) and 0.5 h,
      1.5 h, 4 h, 8 h, 12 h and 24 h after dosing, and urine samples were collected up
      to 24 hours after the dose. The mean +/- SD kinetic parameters were: peak plasma
      level (Cmax) 607 +/- 231 micrograms.l-1 reached in 1.93 +/- 1.39 h (tmax),
      elimination half-life (t1/2) 5.55 +/- 0.98 h, area under the plasma concentration
      time curve (AUC0-infinity) 4,772.1 +/- 1,318.4 micrograms.l-1.h, mean residence
      time (MRT) 8.13 +/- 1.31 h, apparent plasma clearance (Cl/f) 1.27 +/- 0.80 ml.min
      1.kg-1, apparent volume of distribution (Vz/f) 0.60 +/- 0.38 l.kg-1. Urinary
      recovery was 38.4 +/- 9.9% (n = 4) of the dose. Renal clearance was 0.42 +/- 0.10
      ml.min-1.kg-1 (n = 6). No influence of age on the cetirizine parameters was
      evidenced among this group, except for MRT (p < 0.05) which decreases with age.
      When compared with results in adults, elimination half-life (t1/2) was twice as
      short and apparent clearance twice as great. These results suggest that a higher
      dosage b.i.d. may be required in children.

PMID- 7582387
TI  - Pharmacokinetics of lithium in plasma and red blood cells in acute and chronic
      intoxicated patients.
AB  - Lithium disposition in plasma, red blood cells (RBC) and urine was studied in
      acute self-poisoned patients upon chronic lithium therapy (n = 4) and in chronic
      intoxicated patients receiving oral lithium (n = 10). Following acute
      intoxication upon chronic lithium therapy, lithium pharmacokinetics did not
      differ from previous reports. Terminal plasma half-life ranged from 19.0-29.0 h
      and RBC/plasma ratio was 0.32 +/- 0.11. The distribution volume of the terminal
      phase, Vz, was estimated at 0.84 +/- 0.32 l/kg and renal clearance was 0.38 +/-
      0.11 ml/mn/kg. After chronic intoxication lithium pharmacokinetics differed from
      those of the acute patients. Terminal plasma half-life ranged from 36.5-79.4 h
      and zero-order decline appeared in 8 of the 10 patients. The RBC/plasma ratio was
      0.87 +/- 0.22 on admission. Vz was estimated at 0.71 +/- 0.27 l/kg and renal
      clearance was 0.16 +/- 0.07 ml/mn/kg. These modifications in lithium elimination
      kinetics could be related to the decrease in the glomerular filtration rate with
      age or renal dysfunction in this group of patients.

PMID- 7582384
TI  - Comparative bioavailability of a dispersible formulation of diclofenac and
      finding of double plasma peaks.
AB  - We carried out a comparative study of the bioavailability of a typical, enteric
      coated diclofenac with regard to a new dispersible formulation whose faster
      dissolution results in an earlier onset of its analgesic effect. This randomized,
      crossover study was conducted in 12 healthy male volunteers, who received in
      fasting 100 mg of enteric-coated diclofenac (Dolotren, FAES) and 100 mg of
      dispersible diclofenac (Dolotren Dispersable, FAES), with one-week interval
      between both. Blood samples were taken at pre-established times during the 24
      hours after dosing, and plasma concentrations of diclofenac were determined by
      HPLC. Possible adverse experiences were monitored with a check-list, and blood
      and urinalysis were performed for safety assessment. The dispersible formulation
      showed a relative extent of bioavailability between 78% and 99% (90% CI) for the
      AUC0-infinity, being the 90% CI for the Cmax 63%-129%. The time to Cmax (Tmax)
      was significantly shorter with the dispersible than with the enteric-coated
      formulation (95% CI for the difference = 1.5-4.25 hours) as the T0(lag) or time
      to measurable plasma concentrations (1.9-4.2 hours, 95% CI). A relevant feature
      in the study was the finding of a second peak at 2-2.5 hours post-dosing in 7 out
      of 11 profiles of subjects receiving the dispersible formulation. Both
      formulations were well tolerated in clinical and laboratory terms. In conclusion,
      the new dispersible formulation of diclofenac allows absorption to begin more
      rapidly and plasma peak is reached earlier, a fact that may be relevant to the
      analgesic treatment of acute pain.

PMID- 7582386
TI  - Effects of bezafibrate and of 2 HMG-CoA reductase inhibitors on lipoprotein (a)
      level in hypercholesterolemic patients.
AB  - Lp(a) level is relatively stable in each individual and is mainly under genetic
      control. Attempts made to lower Lp(a) with pharmacological means gave conflicting
      results. In order to further evaluate the effect of hypocholesterolemic drugs on
      Lp(a) level, 66 patients with primary hypercholesterolemia were selected. The
      vast majority of the patients had Lp(a) concentration at the low end of the range
      of distribution, 7 had undetectable Lp(a) levels and only 2 had Lp(a) higher than
      30 mg/dl. No relationship was found between Lp(a) level and serum and lipoprotein
      lipids. In 12 patients serum cholesterol was well controlled by diet alone and
      the patients continued the diet for up to 8 months. The other patients were
      randomly subdivided into 3 groups of therapy. The first group received slow
      release bezafibrate 400 mg once a day, the second one pravastatin 20 mg once a
      day and the third one simvastatin 10-40 mg once a day. Drug therapy lasted for 8
      months. At the end of the period, 22 of 29 patients treated with the 2 HMG-CoA
      reductase inhibitors had Lp(a) higher than baseline. The difference was
      statistically significant in both groups of patients. No significant change in
      Lp(a) was observed in diet and in bezafibrate group. Serum and LDL cholesterol
      significantly decreased in all the 3 drug groups. The increase in Lp(a) after the
      2 HMG-CoA reductase was small enough to have negligible effects on cardiovascular
      risk, but raises the problem of the role of LDL receptor in the catabolism of
      Lp(a).

PMID- 7582388
TI  - Azithromycin does not increase plasma concentrations of oral midazolam.
AB  - Interaction between azithromycin and midazolam was investigated in a double
      blind, randomized crossover study of 2 phases. Ten healthy volunteers were given
      azithromycin (500 mg on day 1 and 250 mg on days 2-5) or placebo pretreatments.
      On day 5 they ingested 15 mg midazolam. Plasma samples were collected and
      psychomotor performance measured for 17 h. Azithromycin treatment increased the
      median (range) concentration peak time of midazolam from 1.0 (0.5-2) h to 1.25
      (0.5-5) h and decreased plasma concentrations of midazolam during initial 3 hours
      after the intake of midazolam (p < 0.05). Mean +/- SE mean peak concentration of
      midazolam was decreased from 86 +/- 17 ng ml-1 to 57 +/- 9 ng ml-1 (p < 0.05).
      Azithromycin did neither increase the total area under concentration-time curve
      nor change the elimination half-life of midazolam. In Maddox wing test the
      maximum effects of midazolam were reached later during azithromycin phase, but no
      other changes were observed in pharmacodynamics of midazolam. Azithromycin may
      delay the absorption of midazolam, which can postpone the onset of action of
      midazolam.

PMID- 7582389
TI  - Xylitol-induced increase in the concentration of oxypurines and its mechanism.
AB  - We investigated the effect of xylitol on the plasma concentration and the urinary
      excretion of purine bases, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid in
      subjects who had ingested pyrazinamide (60 mg/kg weight). One liter of 10%
      xylitol was infused intravenously over 2 hours to 5 subjects to whom pyrazinamide
      had been administered 10 hours before. Xylitol increased the plasma concentration
      of uric acid, hypoxanthine and xanthine, the urinary excretion of hypoxanthine
      and a ratio of lactic acid/pyruvic acid in blood, while it decreased the plasma
      concentration and the urinary excretion of inorganic phosphate, 5
      hydroxypyrazinamide and 5-hydroxypyrazinoic acid. These results suggested that in
      addition to an increase in purine degradation by xylitol, xylitol-induced
      increase in the cytosolic NADH inhibited xanthine dehydrogenase activity in the
      liver and the small intestine.

PMID- 7582391
TI  - Three explorative studies on the efficacy of the antihistamine mebhydroline
      (Omeril).
AB  - The efficacy of a multiple oral dose treatment with mebhydroline (Omeril coated
      tablets, 100 mg t.i.d.) was examined in 3 studies which were performed in a
      randomized, double-blind and placebo-controlled 2-way cross-over design. A second
      target was to investigate the suitability of different pharmacodynamic models for
      testing the efficacy of antihistamines. Study A involved a nasal provocation with
      a specific allergen in 11 symptom-free patients suffering from seasonal allergic
      rhinitis. In study B, a nasal provocation with histamine was investigated in 11
      healthy volunteers. Study C involved a cutaneous provocation with a specific
      allergen in 12 symptom-free patients suffering from seasonal allergic
      rhinitis/atopy. The mebhydroline treatment's superiority over placebo was shown
      statistically at the 95% confidence level for the symptoms itchy nose in study A
      and for nasal congestion in study B. In study C, allergen-induced weals
      (planimetric measurement) and itching (visual analog scale) were significantly
      changed by mebhydroline. A qualitative evaluation revealed a reaction intensity
      that differed between the 2 treatments to a clinically relevant degree, however,
      without reaching significance. On the basis of the data it is expected that the
      clinical efficacy of mebhydroline may be further substantiated in confirmatory
      clinical trials which should include placebo and positive controls. The test
      methods used differed in their suitability for measuring the pharmacodynamic
      effects of antihistamines. Overall, the most clear-cut results were seen in hay
      fever patients using a specific allergen for provocation. The planimetric
      assessment of weal response should be preferred as a cutaneous model. Both AR and
      AARM have their clinical relevance. Based on highly significant results of a
      subgroup analysis there are indications in favor to AR, but momentary there is no
      definite conclusion in favor of or against either of the 2 methods.

PMID- 7582390
TI  - Effects of a new calcium channel blocker, MPC-1304, on blood pressure, serum
      lipoproteins and serum carbohydrate metabolism in patients with essential
      hypertension.
AB  - The effects of MPC-1304, a new calcium channel blocker, on blood pressure, serum
      lipoproteins, and carbohydrate metabolism were compared with those of atenolol in
      a group of patients with mild to moderate essential hypertension. Systolic and
      diastolic pressures were significantly decreased by both MPC-1304 and atenolol
      administration. Serum levels of apolipoproteins A-I and A-II were significantly
      increased after 8-12 weeks of MPC-1304 treatment, but were unchanged during a
      similar period of atenolol treatment. Neither drug induced any significant change
      in other lipoprotein parameters, fasting blood sugar, immunoreactive insulin, C
      peptide or HbA1c. No serious side-effects or abnormal laboratory values were
      observed during the course of administration of either drug. These findings
      indicated that MPC-1304 is as efficacious as an antihypertensive drug and is
      without adverse effect on lipoprotein or carbohydrate metabolism.

PMID- 7582393
TI  - A confirmatory strategy for therapeutic equivalence trials.
AB  - In the planning phase of a therapeutic equivalence trial, a range has to be
      specified that defines the parameter region within which the treatments to be
      compared are considered equal for practical purposes. It is current practice in
      equivalence assessment to fix some value for limiting the equivalence range and
      to test the corresponding null hypothesis in confirmatory analysis. This
      procedure is unsatisfactory, if, for example, the drug to be investigated is not
      only equivalent but turns out to be even superior to standard. In this situation
      it would be desirable to test not only for equivalence but also for superiority.
      The paper presents an alternative approach that allows for a flexible handling of
      the problem. If therapeutic equivalence can be established the method
      additionally allows, under maintenance of the multiple level, for testing all
      null hypotheses that correspond to acceptable equivalence ranges and even of
      superiority. Because of the special structure of the hypotheses no alpha
      adjustment is needed for these additional confirmatory analyses.

PMID- 7582396
TI  - Gender related pharmacokinetics of diltiazem in healthy subjects.
AB  - The aim of this study was to investigate the gender-related pharmacokinetic
      differences after a single oral dose of diltiazem (120 mg) in 12 healthy subjects
      (6 males and 6 females). Kinetic parameters were calculated from serum
      concentrations obtained by means of a specific HPLC method. The total area under
      the concentration-time curve (AUC0-infinity) was 917.03 +/- 342.13 ng.h-1/ml for
      females and 1,192.97 +/- 329.93 ng.h-1/ml for males. Peak serum levels (Cmax)
      were 181.29 +/- 48.03 ng/ml and 194.29 +/- 93.81 for females and males,
      respectively. The time to reach maximum concentration (Tmax) was 2.2 +/- 0.8 h
      for both. The biological elimination t1/2 was 4.58 +/- 2.08 h and 5.59 +/- 2.44
      h, showing an elimination rate (kel) of 0.174 +/- 0.062 h-1 and 0.149 +/- 0.075 h
      1, and a mean residence time (MRT) of 8.56 +/- 1.94 h and 8.88 +/- 2.78 h for
      females and males, respectively. Male subjects showed higher values than females,
      but no significant difference was observed when comparing pharmacokinetic
      parameters by gender. Diltiazem was well tolerated by all subjects.

PMID- 7582397
TI  - The effect of estradiol on the production of melatonin in postmenopausal women.
AB  - The influence of two routes of estradiol administration on pineal melatonin
      production in postmenopausal women was investigated. Both transdermal and oral
      estradiol treatment led to an increase as well as decrease of melatonin
      production in different patients. The reason why individuals respond either in a
      stimulatory or inhibitory manner is unknown and requires to be evaluated in
      further more extensive studies.

PMID- 7582392
TI  - Biliary excretion of mezlocillin in patients with hepatic disease.
AB  - In three patients with liver disease (2 patients with alcoholic liver cirrhosis
      and 1 patient with chronic cholangitis) total, renal, biliary and metabolic
      clearance of the acylureidopenicillin mezlocillin was examined under steady state
      conditions. Mezlocillin was infused for 6 hours at a constant infusion rate of 10
      mg/min. Renal clearance was calculated based on urinary excretion rates. Duodenal
      perfusion and marker dilution technique was applied to determine biliary
      excretion rates of the drug. Clearances were estimated by dividing the excretion
      rate by the respective plasma concentration. Total clearance was calculated by
      dividing the infusion rate by the plasma concentration. Biliary clearance was
      markedly reduced in the patients compared to the data of 8 healthy controls (0.65
      +/- 0.33 ml/min vs 98.6 +/- 42.5 ml/min). Total and renal clearance were
      diminished (total clearance: 121.4 +/- 21.6 ml/min vs 286.5 +/- 54.6 ml/min,
      renal clearance, 65.4 +/- 1.0 ml/min vs 137.6 +/- 32.6 ml/min). In contrast,
      metabolic clearance was not changed (53.3 23.1 ml/min vs 50.3 +/ 24.2 ml/min). As
      mezlocillin is well tolerated and has a wide margin of safety we do not recommend
      reduced dosage. On the contrary, it might even be necessary to increase the dose
      when treating biliary tract infections in patients with cholestasis in order to
      assure effective drug concentrations in the bile.

PMID- 7582394
TI  - Effect of tauroursodeoxycholic acid on biliary lipid composition. A dose-response
      study.
AB  - Tauroursodeoxycholic acid has been proposed for the treatment of hepatobiliary
      disease, but data on the enrichment of biliary tauroursodeoxycholic acid pool and
      on changes of biliary lipids after administration of the compound are scarce. We
      studied the composition of biliary lipids in a series of 33 patients with
      radiolucent stones, before and after treatment with tauroursodeoxycholic acid,
      3.5 - 16.6 mg/kg/day for 4 - 6 weeks. Duodenal bile was collected with the Entero
      Test after gallbladder contraction. Tauroursodeoxycholic acid administration
      produced the following dose-dependent effects: a linear decrease of cholesterol
      saturation (r = 0.59, p < 0.001); a non-linear increase of the percent of
      ursodeoxycholic acid in bile (r = 0.59, p < 0.001); a non-linear increase of the
      fraction of ursodeoxycholate conjugated with taurine. At the dose of 11 mg/kg per
      day, cholesterol saturation was 80%, ursodeoxycholic acid represented about 45%
      of biliary bile acids, and about half of UDCA was conjugated with taurine.
      Biliary bile acids were repeatedly measured in 6 patients during long-term
      treatment with 9.7 - 12.1 mg/kg. The fraction of tauroursodeoxycholic acid
      decreased progressively from 67.6% +/- 10.5 to 29.1% +/- 5. Tauroursodeoxycholic
      acid is as effective as ursodeoxycholic acid on a molar basis in reducing biliary
      cholesterol saturation and in enriching bile with ursodeoxycholate. Moreover,
      tauroursodeoxycholic acid administration is associated with higher concentrations
      of tauroconjugates in the bile than those previously reported by feeding the free
      bile acid.

PMID- 7582395
TI  - The assessment of dyspnea in bronchial asthma.
AB  - We report a new quality of life measuring instrument for the self-assessment of
      dyspnea in bronchial asthma patients while performing a daily activities test.
      The instrument was tested for sensitivity to inhaled B-agonist in patients with
      moderate to severe asthma. Results indicated that the new scale was a sensitive
      and simple tool which may be useful in the therapeutic management of bronchial
      asthma.

PMID- 7582399
TI  - A Bayesian approach to drug disposition evaluation: application to teicoplanin.
AB  - We suggest a Bayesian method in order to evaluate the disposition kinetics of the
      drug plasma concentrations after intravenous (i.v.) and/or after extravascular
      administration of the drug in the same subject pooled with information obtained
      taking into account previous pharmacokinetics of the drug. This approach was
      applied to the investigation of teicoplanin pharmacokinetics after 200 mg i.v.
      administration to 10 healthy subjects.

PMID- 7582398
TI  - The effect of enalapril on tyramine induced changes in renal function in man.
AB  - Increasing animal evidence support an important facilitatory interaction between
      angiotensin II and norepinephrine within the kidney. This angiotensin
      II/norepinephrine interaction was investigated in man by examining the effect of
      enalapril pretreatment (5 mg for 5 days) on the renal response to a low non
      pressor dose of intravenous tyramine 4 micrograms/kg/min for 120 min in 8 healthy
      subjects undergoing water diuresis. Tyramine is an indirect sympathomimetic agent
      which causes neuronal release of norepinephrine. Enalapril and tyramine, alone
      and in combination, had no effect on glomerular filtration, effective renal
      plasma flow or sodium excretion. Tyramine caused a significant increase in
      urinary flow rate (p < 0.05) but this was not influenced by enalapril
      pretreatment. The lack of effect of enalapril on the renal response to tyramine
      contrasts with a previous study which examined the effect of enalapril on the
      renal response to circulating norepinephrine. This may suggest that enalapril
      affect renal function only when there is renal vasoconstriction (as with
      norepinephrine) and not when renal blood flow is unchanged (as with tyramine).

PMID- 7582400
TI  - Pharmacokinetic interactions between lithium and fluoxetine after single and
      repeated fluoxetine administration in young healthy volunteers.
AB  - Pharmacokinetic interactions following coadministration of fluoxetine and lithium
      were investigated in 10 young healthy subjects. Both drugs were administered
      orally in a non-blinded design with 3 consecutive treatment periods: single oral
      dose of lithium (32.4 mmol lithium as acetate, Quilonum; coadministration of
      single oral doses of lithium (32.4 mmol) and fluoxetine (Fluctin, 60 mg); and
      single oral dose of lithium after 7-day pretreatment with fluoxetine (20 mg
      t.i.d.). Periods 1 and 2 were separated by a 1-week washout phase, while period 3
      followed on immediately after period 2. Lithium serum concentrations were
      practically identical in periods 1 and 3 (administration of lithium alone and
      after chronic fluoxetine dosing). However, in period 2, when the 2 drugs were
      coadministered as single oral doses, the lithium concentrations were lower in the
      first 4 hours after medication compared with treatment periods 1 and 3. Cmax was
      also significantly lower in period 2. The times to peak, however, were not
      significantly changed by any fluoxetine comedication. The parameters AUC0 -->
      infinity, t1/2, total clearance (Cltot) and renal clearance (Clren) determined
      after administration of lithium alone did not differ statistically from values
      determined after single or after repeated fluoxetine dosing. Coadministration of
      lithium and fluoxetine did not produce any clinically relevant changes in
      hemodynamics, ECGs or laboratory parameters. After single doses of both drugs the
      most frequently reported symptoms were gastrointestinal complaints, while mild
      sedative symptoms were predominant when lithium was given after repeated
      fluoxetine medication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582403
TI  - Subjective perception of additional support requirements of elderly patients
      discharged from accident and emergency departments.
AB  - Fifty per cent of elderly patients discharged from accident and emergency (A&E)
      departments experience functional deterioration and increased dependence; 5.6%
      require readmission within 14 days. Discharge is often to inadequate community
      support. Functional assessment by A&E department staff may identify patients at
      greatest risk. The predictive ability of 25 patients aged 75 years or over to
      identify their additional support requirements following discharge from the A&E
      department was evaluated retrospectively using interview questionnaires 10-20
      days after discharge. A total of 23 patients, of mean age 79.3 years, were
      interviewed. Six patients expressed concern both about coping at home and about
      needing extra support; four of the nine patients who recruited additional help
      were in this group (P = 0.239; n.s.). There was no correlation between additional
      support needed and patients living alone (P = 0.302; n.s.), dependent relative (P
      = 0.325; n.s.) or existing domiciliary support (P = 0.197; n.s.). All patients
      were satisfied with their management, and of the six who expressed concern about
      being able to cope at home, none informed A&E staff. Patients' perception is an
      unreliable indicator of their need for additional help and their ability to
      manage at home after discharge from A&E departments. Additional support
      requirements appear to be unrelated to domestic circumstances.

PMID- 7582402
TI  - The role of CK-MB in chest pain decision-making.

PMID- 7582401
TI  - Effects of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on
      serum lipids, lipoproteins and cholesterol ester transfer activity in primary
      hypercholesterolemic patients.
AB  - Effects of a combination therapy of fluvastatin, a new inhibitor of HMG-CoA
      reductase, and niceritrol on lipid metabolism were investigated measuring a wide
      range of parameters in 42 patients with primary hypercholesterolemia. After a
      wash-out period patients were randomly allocated to 1 of the 2 groups, the
      fluvastatin-preceding group (G-1) and the niceritrol-preceding group (G-2). In G
      1 fluvastatin monotherapy (30 mg/day) significantly decreased total cholesterol
      (TC) and LDL-cholesterol (LDL-C). There was no significant change in HDL
      cholesterol (HDL-C), triglyceride (TG) and lipoprotein (a) (Lp(a)). Further
      effect in HDL-C and TG was observed after the addition of niceritrol (750
      mg/day). On the other hand, in G-2, while niceritrol alone (750 mg/day) produced
      no significant change in TC, LDL-C, HDL-C, TG and Lp(a), the addition of
      fluvastatin (30 mg/day) reduced TC and LDL-C levels significantly. Cholesterol
      ester transfer (CET) activity was significantly reduced by niceritrol
      monotherapy. After the concomitant use of the 2 drugs CET activity was
      significantly reduced only in G-2. No significant change in lipoprotein lipase
      and hepatic triglyceride lipase activities were observed in the 2 groups at
      either point in time. No serious adverse effect was observed in this study. It is
      concluded that fluvastatin is an effective drug for lowering LDL-cholesterol and
      causes no adverse alteration in lipid metabolism. Combination with niceritrol at
      a dose of 750 mg/day dose not appear to augment or attenuate beneficial effects
      of fluvastatin.

PMID- 7582404
TI  - Life support courses for all.
AB  - Many courses teaching advanced life support skills are now available in this
      country. These 'provider' courses include those dealing with cardiac, trauma and
      paediatric resuscitation. The numbers of applicants for all these courses far
      exceed the places available. There is further demand for places from those who
      currently hold advanced life support provider certificates and who require re
      evaluation to maintain their certification. For many, particularly non-medical
      staff, obtaining funding or study leave to attend such a course may also be a
      problem. All these factors lead to delays in providing the training in advanced
      life support skills that is clearly needed. We here report on the development and
      success of local 1-day resuscitation courses as a means of introducing all staff
      who may be expected to cope with an emergency situation to the current principles
      of resuscitation. We do not suggest that such abbreviated courses are in any way
      a substitute for the full advanced life support course, but that they can provide
      tuition that may otherwise be unavailable.

PMID- 7582407
TI  - Pneumatic anti-shock garment--does it have a future?
AB  - A total of 100 accident and emergency (A&E) departments in the UK responded to a
      questionnaire about their use of the pneumatic anti-shock garment (PASG). Less
      than one in 10 departments used PASG in their prehospital care system, less than
      one in five departments used PASG during in-patient care, and there was wide
      variation in PASG usage in those situations for which their use is recommended by
      the Advanced Trauma Life Support (ATLS) course.

PMID- 7582405
TI  - Treatment of knee sprains: modified Robert Jones or elastic support bandage?
AB  - The aim of this investigation was to compare in a prospective randomized study
      the outcome of painful, traumatic knee injuries when treated with either the
      modified Robert Jones (MRJB) or elastic support bandage (ESB). Patients with
      moderate or severe unilateral knee injury presenting to our department within 24
      h were randomized into two treatment groups receiving either the MRJB or an ESB.
      The main outcome parameters of the study were the amount of pain relief required,
      the speed of recovery, mobility and patient preference. The results of our study
      of 40 patients indicate that the two treatments were equally effective in
      treating knee sprains, and patients preferred the ESB in the early post-injury
      period. Therefore, we see no reason to continue using the MRJB for the treatment
      of sprained knees in the accident and emergency (A&E) setting when a more patient
      acceptable, time and cost-effective treatment is available.

PMID- 7582406
TI  - Psychiatric referrals from an accident and emergency department in Singapore.
AB  - A total of 500 consecutive psychiatric referrals from the Accident and Emergency
      (A&D) Department of the National University Hospital of Singapore were studied
      with regard to their demographic characteristics, diagnoses, presenting problems
      and management. There were 314 females (62.8%) and 186 males (37.2%), and the
      mean age of subjects was 35.5 years. The three main diagnoses were anxiety
      disorders (25.6%), depression (19.4%) and schizophrenia (17.6%). About 41% were
      admitted, of whom two-fifths were initially admitted to the medical ward because
      of drug overdose or alcohol intoxication. A further 34% were treated as out
      patients, and 21% were discharged.

PMID- 7582409
TI  - Burns caused by domestic alkalis.

PMID- 7582408
TI  - Urgent full blood count in children over 3 months of age with bacterial
      meningitis.
AB  - Children with bacterial meningitis often have a full blood count (FBC) measured
      urgently on admission. We investigated whether urgent FBC gave results that aided
      immediate management or predicted outcome in children with meningitis. FBCs were
      measured on admission during 190 episodes of bacterial meningitis in children
      admitted between 1984 and 1991. Significant anaemia was found in seven children,
      but immediate transfusion was only necessary in the three subjects who were in
      the Paediatric Intensive Care Unit (PICU). A white blood count of less than 5 x
      10(9) L-1 was significantly associated with death (P < 0.02), but a Glasgow Coma
      Score of less than 8 predicted death more accurately (positive predictive value
      of 40%). FBC yielded immediately useful information only in the 15% of children
      who were admitted to PICU. Conscious level was a better predictor of outcome than
      FBC. We recommend that urgent FBC should be performed in children with meningitis
      admitted to a PICU; in other children with meningitis FBC can be analysed during
      normal laboratory hours.

PMID- 7582410
TI  - Changing standards for thrombolysis in accident and emergency departments.

PMID- 7582411
TI  - Chainsaw penetrating neck injury.
AB  - A case of chainsaw injury to the neck is described. Previous reports in the
      English language are exceedingly rare. A brief discussion of safety features on
      chain saws is followed by a review of selective vs. mandatory surgical
      exploration in penetrating neck trauma, including the role of ancillary
      diagnostic tests.

PMID- 7582413
TI  - Rhabdomyolysis following acute alcohol intoxication.
AB  - The case of a fit young man who developed rhabdomyolysis after a short period of
      immobilization following acute alcohol intoxication is described. Rhabdomyolysis
      should be considered in an intoxicated patient presenting with muscle tenderness,
      particularly after immobilization.

PMID- 7582414
TI  - Pharyngeal perforation: an easily missed finding following intra-oral injury.
AB  - A 2-year-old child presented with pharyngeal perforation following a peroral
      injury with a toothbrush. Direct force applied to an object such as a toothbrush
      in the mouth may cause either superficial or penetrating injury within the
      oropharynx. A high index of suspicion is sometimes necessary to identify a
      pharyngeal perforation and if this is diagnosed we would advocate admission to
      hospital, restriction of oral intake, intravenous fluids and antibiotics, with
      close observation to ensure that healing occurs without development of further
      complications.

PMID- 7582412
TI  - Extreme methaemoglobinaemia secondary to recreational use of amyl nitrite.

PMID- 7582415
TI  - Foreign body detected by patients using metal detectors.
AB  - A positive response from a metal detector when run over an area of the body is a
      strong positive indicator of the presence of a metallic object. If there is a
      possibility of a buried metallic foreign body this positive finding should not be
      ignored.

PMID- 7582416
TI  - Unusual presentation of tuberculosis to the accident and emergency department.
AB  - A patient with localized, reactive tendinitis secondary to tuberculosis presented
      to the accident and emergency (A&E) department. Tendinitis is a relatively common
      complaint, and it is important to consider uncommon systemic causes, including
      tuberculosis.

PMID- 7582417
TI  - Orbital cellulitis demands early recognition, urgent admission and aggressive
      management.
AB  - Orbital cellulitis is an emergency. Confusion still exists between the diagnosis
      of this serious condition and that of preseptal cellulitis. Delay in treatment
      may cause blindness and progression to life-threatening sequelae such as brain
      abscess, meningitis or cavernous sinus thrombosis. We report a case in which,
      despite late referral, emergency surgical intervention was sight saving.

PMID- 7582418
TI  - Near-fatal aspiration of a child's dummy: design fault or deliberate injury?
AB  - A case is described of near fatal aspiration of a child's dummy. This caused
      extensive injuries to the mouth and pharynx and acute respiratory embarrassment
      necessitating admission to a paediatric intensive care unit, and multi
      disciplinary assessment. A design fault in the dummy is discussed, and it is
      recommended that the British Standards specification for dummies be changed.
      Finally, the issue of non-accidental injury is discussed, with the suggestion
      that injuries to the soft tissues of the mouth and pharynx be treated with the
      same degree of suspicion as any other childhood injury.

PMID- 7582419
TI  - Winging of the scapula: an unusual complication of chest tube placement.
AB  - Chest tube insertion is generally considered a safe procedure. We describe a
      patient who developed winging of the scapula following chest tube insertion. This
      complication has not been documented before.

PMID- 7582420
TI  - Another cause for acute carpal tunnel syndrome: tricyclic overdose.

PMID- 7582422
TI  - Head injuries and the observation ward.

PMID- 7582421
TI  - Plaster checks.

PMID- 7582423
TI  - What should doctors wear in the accident and emergency department? Patients'
      perception.

PMID- 7582424
TI  - Trauma team concepts in the UK: tailoring resources to meet demand.

PMID- 7582426
TI  - [Childhood tuberculosis in Spain].

PMID- 7582428
TI  - [Respiratory symptoms in a pediatric population].
AB  - With the aim of determining the prevalence of respiratory symptoms and rhinitis
      among adolescents in Spain, we sent a brief questionnaire about respiratory
      symptoms to all school children (9,644) in the sixth, seventh and eight grades in
      our city. We identified a symptomatic group (SG) consisting of adolescents who
      reported having had one or more of the following three signs within the past 12
      months: a) waking with a feeling of stuffiness; b) experiencing an asthma attack,
      or c) taking medication for asthma. Returned questionnaires accounted for 74.4%
      of those distributed. The following symptoms were reported: wheezing by 13.4%,
      nighttime oppression by 8.4%, stuffiness at night by 7.3%, nighttime coughing by
      24.8%, asthma attack by 4.5%, taking asthma medication by 6.1% and seasonal
      rhinitis by 15.4%. The proportion of symptomatic children was 11.6% (833). All
      symptoms studied that were not required for inclusion in SG correlated highly
      with that group (p < 0.0001). Neither age nor sex were related to inclusion.

PMID- 7582427
TI  - [The prevalence of tuberculous infection in the 6- to 7-year-old schoolchild
      population in Albacete].
AB  - To analyze the prevalence of tuberculosis infection, tuberculin tests were given
      to 3,292 elementary school children in the first and second grades in the
      environs of Albacete (Spain) in 1992. There were 1,532 children aged 6 (122
      vaccinated with BCG) and 1,760 children aged 7 (162 vaccinated); 51 children
      tested positive (20 who had been vaccinated and 31 who had not been). The
      prevalence of infection was 0.78% at 6 years of age and 1.25 at 7 years of age in
      non vaccinated children, a rate similar to that found by earlier national
      surveys. One case of active pulmonary tuberculosis was identified. Inclusion of
      the 8.6% who had been vaccinated caused significant distortion of the initial
      prevalences. The annual rate of infection, estimated based on an annual decline
      of 4%, was 0.143 %. Differences in tuberculosis infection by family socioeconomic
      level, as indicted by level of parental studies or place of residence, were not
      statistically significant, although we did observe a slightly greater rate among
      children living in poorer areas and with parents with only elementary school
      education. Our results confirm a downward trend in the prevalence of tuberculosis
      infection in the population studied, as well as the importance of carrying out
      this type of survey to provide a reference for active control and for taking an
      active stand.

PMID- 7582425
TI  - Anaphylactic shock: mechanisms and treatment.
AB  - This paper reviews the mechanisms of anaphylactic shock in terms of the
      immunoglobulin and non-immunoglobulin triggering events, and the cellular events
      based on the rise in intracellular cyclic AMP and calcium that release preformed
      granule-associated mediators and the rapidly formed, newly synthesized mediators
      predominantly based on arachidonic acid metabolism. These primary mediators
      recruit other cells with the release of secondary mediators that either
      potentiate or ultimately curtail the anaphylactic reaction. The roles of these
      mediators in the various causes of cardiovascular collapse are examined. The
      treatment of anaphylactic shock involves oxygen, adrenaline and fluids. The
      importance and safety of intravenous adrenaline are discussed. Combined H1 and H2
      blocking antihistamines and steroids have a limited role. Glucagon and other
      adrenergic drugs are occasionally used, and several new experimental drugs are
      being developed.

PMID- 7582429
TI  - [Muscle relaxants in the morphometric study of the respiratory muscles in human
      beings].
AB  - The morphological examination of respiratory muscle can be affected by muscular
      contraction following biopsy. Most morphometric studies of respiratory muscles,
      however, have been carried out without taking into account this factor, the
      effect of which can be reduced by using relaxants when taking samples. Objective.
      To examine the effect of using a relaxant in the morphometric analysis of muscle
      fibers. We examined 31 muscle samples from 7 patients. Immediately after removal,
      each pipe was divided in half. One was placed in an isotonic physiological
      solution and the other in a solution of curare 0.02%. Later, both samples were
      processed for morphometric study with ATP-ase, NADTH and PAS tincture.
      Morphological data recorded for the different types of fibers included
      measurement of minimum diameter (Dmin), atrophy and hypertrophy indices (AI and
      HI) and heterogeneity of distribution (SDDmin). The Dmin was smaller in fibers
      transported in a curare solution than in those transported in physiological
      solution (67 +/- 2 microns vs. 71 +/- microns, p < 0.05). The same was true of
      SDDmin (13 +/- 3 vs. 12 +/- 3, p < 0.05), HI (300 +/- 88 vs. 457 +/- 107, p <
      0.05). Likewise, we found a similar direct correlation between size of fibers
      processed with physiological solution and those processed in curare (Dmin, r =
      0.731, p < 0.001; HI, r = 0.827, p < 0.001; SDDmin, r = 0.636, p < 0.0001). The
      use of relaxants in processing muscle samples prevents contraction and should be
      used systematically in the morphological analysis of muscle fibers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582430
TI  - [A technical evaluation of 5 brands of O2 concentrators. The Asturias Project].
AB  - To check the technical specifications of 5 O2 concentrators pertaining to 5
      different brands: Mark 4, Zefir, Puritan-Bennet, Drager and MHF prototype. The
      concentrators worked continuously for 37 days. External filters were cleaned
      after 400 hours and measurements were taken when theoretical flows were between 1
      and 3 l/min. One-way analysis of variance and Scheffe's method were used to
      compare the different brands. Flow measurements were taken with Costrema and
      Drager debitmeters. O2 concentrations were measured with Drager, Cepo and Oxidig
      oximeters. Emitted sound was measured with Cel, Spyri Ag Thun, Bruel Kjaer and
      General Radio meters. Electrical consumption was determined with a Siemens
      counter. All the concentrators produced flows that were under theoretical values,
      though the Zefir and MHF models came the closest. Accuracy and precision of flow
      varied from 1% to -32%, and from 1.1% to 11.7%, respectively. The value of 4
      expressing linearity of flows oscillated between 0.959 and 0.991. When flow was 2
      l/min or less, all achieved O2 concentrations greater than 90%, but this level
      was reached only by the Drager and MHF concentrators when flows were 3 l/min.
      With the exception of the MHF prototype, all the models emitted noise over 50 dB,
      the Drager machine being the noisiest. Electrical consumption was similar in all
      models. O2 concentrators can be recommended as sources of oxygen supply, but they
      have their limitations. Improvements must be made in accuracy of flow and
      monitoring of the apparatus ability to concentrate; noise must be reduced as
      well.

PMID- 7582431
TI  - [Assisted ventilation via nasal mask in patients hospitalized in a pneumology
      ward for decompensation of their chronic air-flow obstruction].
AB  - Our aim was to evaluate the efficacy of assisted ventilation through a nasal mask
      (AVN) in treating chronic obstructive pulmonary disease (COPD) patients who were
      admitted to a pneumology ward due to decompensation, with PaCO2 > 60 mmHg and pH
      < 7.35. We studied 13 COPD patients who were first observed for 1-2 days until
      adaptation and then given 2 daily sessions of AVN lasting 4 hours with double
      positive pressure (DP90) devices through Sullivan mask with a cannula for
      hyperoxia. Gasometric readings were recorded, along with subjective assessment of
      condition and problems with the mask. Gasometric readings were taken as follows:
      the first upon admission to the ward (AW), the second with AVN 2 days after
      adaptation and the third 3 hours after the second (POST). Statistical analysis
      was with a Student t-test for paired series. Mean age was 64 +/- 3 years and FEV1
      was 0.69 +/- 0.14 l. Interruptions were due to the need for mouth opening even at
      minimum pressures, and the inability to adapt to the consequent tachypnea. No
      other problems were reported by the remaining patients and all perceived
      improvement subjectively. The pH of 7.29 +/- 0.03 at AW increased to 7.41 +/-
      0.03 with AVN (p < 0.001) and held steady at 7.39 +/- 0.01 at POST (p < 0.001
      POST-AW and p = NS POST-AVN). PaO2/FiO2 was 223 +/- 49 mmHg at AW and 267 +/- 41
      mmHg at the POST reading (p = 0.06). PaO2 with AVN was 67 +/- 8 mmHg.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582432
TI  - [The impact of our journals].

PMID- 7582433
TI  - [The contributions of Arabic medicine to pneumology (the 8th-13th centuries)].

PMID- 7582435
TI  - [Dysphonia produced by corticoid inhalation: truth or myth?].
AB  - One of the undesirable side-effects usually related to the administration of
      inhaled corticoids is the development of dysphonia. This association has been
      attributed to the effect of the corticoid on vocal muscles. We present 5 asthma
      patients who all developed dysphonia at some time. All were examined by video
      laryngostroboscope. Abundant mucus on the vocal cords was observed in 4 patients,
      and small vocal nodules as well as mucus was seen in 2. We believe that dysphonia
      is transitory in these patients and is related to the presence of mucus that
      prevents correct closure of the glottis. Corticoids are not only not
      contraindicated in such cases, but their continued use would also benefit the
      condition of dysphonia as asthmatic inflammation improves.

PMID- 7582434
TI  - [The usefulness of 99mTc-tetrofosmin in the diagnosis of pulmonary tumors. A
      preliminary assessment].
AB  - We conducted a preliminary study of captation of the new radiopharmaceutical
      99mTc-tetrofosmin in cases of primary carcinoma of the lung, analyzing the
      results of 5 cases studied before surgery with single photon emission tomography
      (SPECT) of the lung. The results obtained by imaging were compared with those
      from surgery. Tumor size ranged between 3.5 and 9 cm. In all cases the images
      showed that captation of the radiotracer by the neoplasm was satisfactory,
      leaving the area of the tumor clearly distinguishable from normal adjacent lung
      tissue and giving no signs of interference caused by absorption of 99mTc
      tetrofosmin by contiguous structures (heart or liver). Based on these preliminary
      results we assert that SPECT of the lung using 99mTc-tetrofosmin may be useful in
      the clinical diagnosis of malignant lung tumors, although further research must
      determine to what extent the technique can be relied upon.

PMID- 7582437
TI  - [Tracheal rupture secondary to intubation or tracheostomy].
AB  - This article describes our experience with 3 cases of iatrogenic rupture of the
      trachea (2 cases secondary to orotracheal intubation and 1 to tracheostomy), all
      of which required surgery. We discuss the indications for surgical treatment and
      the technique of choice, and review the literature. Based on our experience we
      advise early intervention and direct suture of the lesion; if mechanical support
      ventilation is needed, we advise using a tube with low-pressure pulmonary
      tamponade.

PMID- 7582436
TI  - [An intrathoracic meningocele in von Recklinghausen's disease. A case report].
AB  - Posterior mediastinal tumors in young people are most often neurogenic. The
      presence of a meningocele has occasionally been described as causing mass in the
      region and cases reported have mainly been in patients with neurofibromatosis. We
      describe a patient with type I neurofibromatosis and intrathoracic meningocele.

PMID- 7582438
TI  - [Traumatic hemothorax treated by video-assisted thoracoscopic surgery].
AB  - The introduction of video-assisted thoracic surgery (VTS) has significantly
      furthered the use of the thoracoscope in surgery. In the case we describe, a 79
      years-old man at high risk for surgery came to our hospital with hemothorax due
      to trauma. The necessary procedure was performed successfully with VTS, which
      allowed for the repair of an acute condition that would otherwise have been
      treated conventionally by way of posterolateral thoracotomy. We conclude that VTS
      may play an important role in the diagnosis and treatment of certain thoracic
      injuries, so that surgery involving more extensive bleeding is rendered
      unnecessary.

PMID- 7582440
TI  - [Bronchiectasis and alpha 1-antitrypsin deficiency].

PMID- 7582441
TI  - [Bronchiolitis obliterans and organized pneumonia: 2 clinico-histological
      entities of the pulmonary acinus].

PMID- 7582439
TI  - [Recurrent amiodarone lung toxicity after withdrawal of the drug and treatment
      with corticoids].
AB  - We present a case of recidivation in amiodarone-induced pulmonary toxicity 4
      months after suspension of the drug, while treatment with corticoids was
      underway. Possible causes suggested are the persistence of high blood levels of
      amiodarone and the rapid decrease of corticoid dose.

PMID- 7582442
TI  - [Pleural effusion associated with vertebral osteomyelitis].

PMID- 7582443
TI  - [Pseudochylothorax or cholesterol pleural effusions].

PMID- 7582444
TI  - Mexiletine-induced shortening of the action potential duration of ventricular
      muscles by activation of ATP-sensitive K+ channels.
AB  - A class Ib antiarrhythmic drug, mexiletine (100 microM) significantly shortened
      the action potential duration (APD) of guinea-pig ventricular muscles and this
      effect was completely abolished in the presence of glibenclamide (50 microM), a
      blocker of the ATP-sensitive K+ channel (KATP). Mexiletine significantly
      increased the open probability of uridine diphosphate-primed KATP channels,
      recorded in inside-out patches of the ventricular cells. The results suggest that
      mexiletine shortens the APD of ventricular muscles, at least in part, via
      activation of KATP.

PMID- 7582446
TI  - Direct demonstration of sulphonylurea-sensitive KATP channels on nerve terminals
      of the rat motor cortex.
AB  - We examined whether ATP-sensitive potassium (KATP) channels are present on
      presynaptic terminals of the rat motor cortex, an area of the CNS exhibiting a
      high density of sulphonylurea binding. A novel fused nerve terminal preparation
      was developed which produced structures amenable to patch clamp methods. In
      inside-out recordings a K+ channel was observed which possessed all the major
      features of the Type 1 KATP channel, including sensitivity to ATP and the
      antidiabetic sulphonylureas.

PMID- 7582445
TI  - Promotion by SR 48692 of gastric emptying and defaecation in rats suggesting a
      role of endogenous neurotensin.
AB  - We investigated the influence of the nonpeptide neurotensin receptor antagonist,
      SR 48692, administered orally, on gastric emptying and on acute defaecation. SR
      48692 dose-dependently (ED50 approximately 0.7 microgram kg-1) increased gastric
      emptying of a food suspension, but it had no effect on that of a non-caloric
      meal. SR 48692 also dose-dependently promoted defaecation and increased faecal
      water content. We suggest that antagonism of endogenous neurotensin accounts for
      the gastric emptying and defaecation promoting action of SR 48692.

PMID- 7582447
TI  - GABA-mediated inhibition of the anaphylactic response in the guinea-pig trachea.
AB  - 1. In sensitized guinea-pigs, the effects of gamma-aminobutyric acid (GABA) and
      GABAmimetic drugs have been investigated on tracheal segments contracted by
      cumulative application of an allergen (ovoalbumin, OA) and on serosal mast cells.
      The same drugs have also been tested on activation of alveolar macrophages
      isolated from unsensitized guinea-pigs. 2. Superfusion with GABA (1-1000 microM)
      reduced the contraction intensity of tracheal strips. The effect of GABA (100
      microM) was not affected by the carrier blockers, nipecotic acid and beta-alanine
      (300 microM each). It was mimicked by the GABAB agonist (-)-baclofen (100 microM)
      but not 3-aminopropanephosphinic acid (100 microM, 3-APA). The GABAA agonist,
      isoguvacine (100 microM) did not exert any effect. GABA (10 microM)-induced
      inhibition of tracheal contractions was reduced by the GABAB antagonist, 2
      hydroxysaclofen (100 microM, 2-HS), but not by the GABAA antagonist, bicuculline
      (30 microM). 3. The reduction in contraction intensity induced by GABA (100
      microM) was prevented by a 40 min preincubation of tracheal strips with capsaicin
      (10 microM), but not tetrodotoxin (TTX, 0.3 microM). The effect of GABA (1000
      microM) was absent after preincubation with indomethacin (2.8 microM) but
      unmodified when nordihydroguaiaretic acid (NDGA, 3.3 microM) was used. Finally,
      removal of the epithelium prevented the GABA effect. 4. Anaphylactic histamine
      release from serosal mast cells isolated from sensitized animals was not affected
      either by GABA (10-1000 microM) or the selective receptor agonists (-)-baclofen
      (0.1-1000 microM) and isoguvacine (10-1000 microM). The release of platelet
      activating factor (PAF) from alveolar macrophages stimulated by formyl-Met-Leu
      Phe (FMLP; 1 microM) was modified neither by GABA (100 microM)nor by (-)-baclofen
      (100microM).5. In conclusion, these data show that GABA can inhibit allergic
      phenomena in the guinea-pig airways through activation of GABAB receptors. An
      involvement of neuropeptidergic sensory structures is suggested but a role for
      epithelial cells and arachidonate metabolites is not definitely proved.

PMID- 7582448
TI  - Improved survival and reversal of endothelial dysfunction by the 21-aminosteroid,
      U-74389G in splanchnic ischaemia-reperfusion injury in the rat.
AB  - 1. Anaesthetized rats subjected to total occlusion of the superior mesenteric
      artery and the coeliac trunk for 45 min developed a severe shock state
      (splanchnic artery occlusion, SAO shock) resulting in death within 70-90 min
      after release of the occlusion. Sham-operated animals were used as controls. 2.
      Survival rate, survival time, serum tumour necrosis factor (TNF-alpha), white
      blood cell (WBC) count, mean arterial blood pressure (MAP), plasma malonyladehyde
      (MAL); myeloperoxidase activity (MPO) and the responsiveness to acetylcholine
      (ACh 10 nM-10 microM) of aortic rings were investigated. 3. SAO shocked rats had
      a decreased survival rate and survival time (74 +/- 10 min, while sham-shocked
      rats survived more than 4 h), reduced mean arterial blood pressure, increased
      serum levels of TNF-alpha (267 +/- 13 u ml-1) and plasma levels of MAL (57 +/- 7
      nmol ml-1), enhanced MPO activity in the ileum (0.23 +/- 0.04 u x 10(-3) g-1
      tissue) and in the lung (2.2 +/- 0.8 u x 10(-3) g-1 tissue), leukopenia and
      reduced responsiveness to ACh of aortic rings. 4. The 21-aminosteroid U-74389G
      (30 mg kg-1, i.v.) increased survival (survival time = 232 +/- 15 min), lowered
      the serum levels of TNF-alpha and the plasma levels of MAL, reduced leukopenia
      and MPO activity both in the ileum (0.021 +/- 0.004 u x 10(-3) g-1 tissue) and in
      the lung (0.23 +/- 0.03 u x 10(-3) g-1 tissue), improved MAP and restored the
      responsiveness to ACh of aortic rings. 5. Our data suggest that U-74389G is a
      potent lipid peroxidation inhibitor and that it has antishock and endothelial
      protective actions.

PMID- 7582449
TI  - Cytokine-mediated induction of cyclo-oxygenase-2 by activation of tyrosine kinase
      in bovine endothelial cells stimulated by bacterial lipopolysaccharide.
AB  - 1. The induction of cyclo-oxygenase-2 (COX-2) afforded by bacterial
      lipopolysaccharide (LPS, endotoxin) in bovine aortic endothelial cells (BAEC) is
      mediated by tyrosine kinase. LPS also causes the generation of several cytokines
      including interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF
      alpha), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).
      This study investigates whether endogenous IL-1 beta, TNF-alpha, EGF or PDGF
      contribute to the induction of COX-2 elicited by LPS in BAEC and if their action
      is due to activation of tyrosine kinase. Furthermore, we have studied the
      induction of COX-2 by exogenous cytokines. 2. Accumulation of 6-oxo-prostaglandin
      (PG) F1 alpha in cultures of BAEC was measured by radioimmunoassay at 24 h after
      addition of either LPS (1 microgram ml-1) alone or LPS together with a polyclonal
      antibody to one of the various cytokines. In experiments designed to measure 'COX
      activity', 6-oxo-PGF1 alpha generated by BAEC activated with recombinant human IL
      1 beta, TNF-alpha, EGF or PDGF for 12 h was measured after incubation of washed
      cells with exogenous arachidonic acid (30 microM for 15 min). Western blot
      analysis determined the expression of COX-2 protein in BAEC. 3. The accumulation
      of 6-oxo-PGF1 alpha caused by LPS in BAEC was attenuated by co-incubation with
      one of the polyclonal antibodies, anti-IL-1 beta, anti-TNF-alpha, anti-EGF, anti
      PDGF or with the IL-1 receptor antagonist, in a dose-dependent manner. Exogenous
      IL-1 beta, TNF-alpha or EGF also caused an increase in COX activity, while PDGF
      was ineffective. The increase in COX activity elicited by IL-1,beta(10 ng ml-1),
      TNF-alpha (100 ng ml-1) or EGF (1000 ng ml-1) in BAEC was attenuated by erbstatin
      (0.005 to 5 microg ml-1), as was the expression of COX-2 protein measured by
      Western blot analysis.4. PDGF (10 ng ml-1) significantly augmented the rise in
      COX activity and COX-2 protein caused by shorter incubation of BAEC with LPS (1
      microg ml-1 for 3 h). Combination of PDGF (10 ng ml-1) with a low concentration
      of IL-l beta (1 ng ml-1) for 12 h, also increased 'COX activity', but combination
      of PDGF and TNF-alpha (10 ng ml-1) did not show any increased activity.5. These
      results suggest that (i) the induction of COX activity and COX-2 protein elicited
      by LPS in BAEC is mediated by TNF-alpha with lesser contributions from PDGF, EGF
      or IL-1 beta; (ii) exogenous IL-1 beta,TNF-alpha or EGF alone induce COX-2
      activity and protein in BAEC; (iii) PDGF synergizes with IL-1 beta,but not TNF
      alpha, to cause expression of COX-2; and (iv) the induction of COX-2 protein and
      activity caused by these cytokines involves the activation of tyrosine kinase.

PMID- 7582450
TI  - Effect of diabetes and elevated glucose on nitric oxide-mediated
      neurotransmission in rat anococcygeus muscle.
AB  - 1. Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus
      muscle from 8-week streptozotocin-induced diabetic rats. This study investigated
      the effects of insulin treatment, and the duration of diabetes on this
      impairment. In addition, the effect of in vitro exposure to elevated glucose has
      been investigated on NO-mediated relaxations, in muscles from untreated rats. 2.
      Relaxant responses to field stimulation (0.5-5 Hz, 10s train), sodium
      nitroprusside (SNP; 5 and 10 nM) and NO (1 and 3 microM) were significantly
      impaired in anococcygeus muscles from 8-week diabetic rats, compared to responses
      from control rats. Insulin treatment (5 u Lente day-1, s.c.) of diabetic rats
      prevented the development of this impairment. 3. Consistent with findings in 8
      week diabetic rats, relaxation induced by field stimulation, SNP and NO were
      attenuated in tissues from 2-week and 4-week diabetic rats compared to
      corresponding control responses, whereas relaxations to papaverine (3 and 10
      microM) were not reduced. In contrast, diabetes of 3-days duration did not affect
      relaxations to field stimulation, SNP or NO. 4. Incubation of anococcygeus
      muscles from untreated rats in medium containing elevated glucose (44.1 mM) for 6
      h, significantly impaired relaxations to field stimulation compared to responses
      obtained after normal glucose (11.1 mM) incubation. Relaxations to SNP and to NO
      were not affected by 6 h exposure to elevated glucose. Similarly, incubation in
      hyperosmolar solutions containing mannose or sucrose for 6 h, impaired
      relaxations to field stimulation, but not to SNP or NO. 5. The results indicate
      that the diabetes-induced impairment of NO-mediated neurotransmission in the rat
      anococcygeus muscle develops between 3 days and 2 weeks after the induction of
      diabetes with streptozotocin. Prevention of the impairment by insulin treatment
      suggests that it is specific for the diabetic state. In addition, the impairment
      may be related to hyperglycaemia and the consequent rise in osmolarity, since in
      vitro exposure to high glucose as well as to other hyperosmolar media impaired NO
      mediated relaxations to field stimulation.

PMID- 7582452
TI  - Biphasic inhibition of stimulated endogenous dopamine release by 7-OH-DPAT in
      slices of rat nucleus accumbens.
AB  - 1. Fast cyclic voltammetry was used to investigate the effect of 7-OH-DPAT (7
      hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative D3 receptor agonist, on
      electrically stimulated endogenous dopamine release in slices of rat nucleus
      accumbens. 2. 7-OH-DPAT inhibited single pulse stimulated dopamine release in a
      concentration-dependent manner with a maximum inhibition of 95.5%. Analysis of
      concentration-response curves to 7-OH-DPAT showed that they were biphasic, with
      the high affinity component contributing 18.0% to the total inhibition and the
      low affinity component 77.5%. 7-OH-DPAT exhibited a 560 fold selectivity between
      the high and low affinity components (0.015 nM compared to 8.4 nM). 3.
      Concentration-response curves to the non-selective D2/D3 agonist, apomorphine,
      were monophasic. The maximum inhibition was 93.1% and the EC50 value 82 nM. 4.
      The selective D2 antagonist, haloperidol (30 nM), antagonized the low affinity
      component of the concentration-response cuve to 7-OH-DPAT whilst the high
      affinity component was essentially unaffected. The pKB values calculated for the
      high and low affinity components were 7.89 and 9.45 respectively. 5. In
      conclusion, these results demonstrate that 7-OH-DPAT inhibits stimulated dopamine
      release by acting at two different sites. Furthermore, the results are consistent
      with the hypothesis that the high and low affinity components of the
      concentration-response curve to 7-OH-DPAT may reflect activation of functional D3
      and D2 release-regulating autoreceptors respectively. However, the possibility
      that the biphasic nature of the curve may reflect different subtypes of the D2
      receptor cannot be excluded.

PMID- 7582451
TI  - Effects of vitamin E deficiency on vasomotor activity and ultrastructural
      organisation of rat thoracic aorta.
AB  - 1. The effects of vitamin E deficiency were evaluated in aortic rings isolated
      from rats maintained on a diet deficient in vitamin E. 2. Endothelium-dependent
      vasodilator responses to acetylcholine (ACh) and calcium ionophore, A23187, were
      reduced in preparations from treated animals, compared to the age-matched
      controls. The maximal vasodilation to ACh was 66.4 +/- 9 (n = 4) and 38.8 +/- 7
      (n = 4) % in control and 10 month-treated preparations, respectively. 3. The
      endothelium-independent vasodilator responses to sodium nitroprusside as well as
      the concentration-dependent contractile responses to noradrenaline, did not
      differ between treated and control preparations. 4. Electron microscopic
      examination of vascular segments and revealed that, following vitamin E
      deficiency, normal tissue organisation was disrupted, the endothelial monolayer
      either not being in contact with the underlying tissue or being absent in most of
      the areas analysed. 5. It is concluded that during vitamin E deficiency both
      morphological disruption and functional impairment of endothelium occur without
      observable modification of muscle cell function and morphology.

PMID- 7582453
TI  - Discrimination between UTP- and P2-purinoceptor-mediated depolarization of rat
      superior cervical ganglia by 4,4'-diisothiocyanatostilbene-2,2'- disulphonate
      (DIDS) and uniblue A.
AB  - 1. Using a grease-gap recording technique we have investigated the effects of
      some antagonists of P2-purinoceptors on the depolarization of the rat isolated
      superior cervical ganglion evoked by 100 microM alpha, beta-methylene-adenosine
      5'-triphosphate (alpha,beta-MeATP) or uridine 5'-triphosphate (UTP). The effects
      of the putative P2Z-purinoceptor antagonist, coomassie brilliant blue G, putative
      P2X-purinoceptor antagonist, 4,4'-diisothiocyanatostilbene-2,2'-disulphonate
      (DIDS) and uniblue A (an analogue of the P2Y- and P2X-purinoceptor antagonist
      reactive blue 2) were investigated. 2. At the highest concentration examined
      uniblue A (300 microM) depressed alpha,beta-MeATP-induced depolarization and at
      100 and 300 microM enhanced UTP-evoked depolarizations. Coomassie brilliant blue
      G (1 and 10 microM) did not affect depolarizations evoked by alpha,beta-MeATP or
      UTP. Depolarizations evoked by potassium (5 mM) or muscarine (100 nM) were
      unaltered by either coomassie brilliant blue G or uniblue A. Uniblue A (100 and
      300 microM) produced a concentration-dependent depression of hyperpolarizations
      evoked by adenosine (100 microM) whereas coomassie brilliant blue G at up to 10
      microM, did not alter adenosine-induced hyperpolarizations. 3. DIDS (30 and 100
      microM) did not alter adenosine-evoked hyperpolarizations, or depolarizations
      evoked by potassium or UTP. DIDS at 100 microM did not alter depolarizations
      evoked by muscarine. In contrast DIDS produced a concentration-dependent
      depression of alpha,beta-MeATP-evoked depolarizations. 4. These results are
      consistent with the proposal that uniblue A and DIDS but not coomassie brilliant
      blue G are antagonists of P2-purinoceptors and that uniblue A is also an
      antagonist at P1-purinoceptors present on the rat superior cervical ganglion. 5.
      The ability of uniblue A and DIDS to distinguish between depolarizations evoked
      by UTP and alpha,beta-MeATP provides further justification for the proposal that
      these nucleotides activate separate receptors present on the rat superior
      cervical ganglion, i.e. pyrimidinoceptors and P2-purinoceptors respectively.

PMID- 7582455
TI  - The effect of opiates on the terminal nerve impulse and quantal secretion from
      visualized amphibian nerve terminals.
AB  - 1. Secretion of transmitter from amphibian motor nerve terminal release sites is
      intermittent, spatially non-uniform and varies considerably throughout the year
      and during development. The role of opioid receptors in modulating transmitter
      secretion from amphibian motor nerve terminals is evaluated in this study. 2.
      Dynorphin-A (24 microM) and morphine (500 microM) did not significantly change
      the shape of the nerve impulse or the consistency with which it was observed, but
      decreased evoked quantal secretion by more than 50%. These effects of dynorphin-A
      and morphine were largely reversed by naloxone (50 microM). 3. Dynorphin-A and
      morphine did not significantly change either the amplitude or the frequency of
      spontaneous quantal secretions. 4. There was a uniform decrease in evoked quantal
      secretion from release sites along terminal branches, irrespective of the quantal
      content value before drug treatment, indicating no difference in the
      susceptibility of proximal vs distal release sites to opiates. 5. Increasing the
      extracellular calcium concentration (0.3 to 0.4 mM) or trains of conditioning
      test impulses (25 to 100 Hz) resulted in smaller dynorphin-A or morphine-induced
      decreases in evoked quantal secretion. 6. The decrease in evoked quantal
      secretion occurs as a result of a uniform decrease in the probability of quantal
      secretion from release sites without any affect on the propagation of the nerve
      terminal impulse. Low probability release sites become effectively silent.

PMID- 7582454
TI  - Activation of rabbit platelets by Ca2+ influx and thromboxane A2 release in an
      external Ca(2+)-dependent manner by zooxanthellatoxin-A, a novel polyol.
AB  - 1. Zooxanthellatoxin-A (ZT-A), a novel polyhydroxylated long chain compound,
      isolated from a symbiotic marine alga Simbiodinium sp., caused aggregation in
      rabbit washed platelets in a concentration-dependent manner (1-4 microM),
      accompanied by an increase in cytosolic Ca2+ concentration ([Ca2+]i). 2. ZT-A did
      not cause platelet aggregation or increase [Ca2+]i in a Ca(2+)-free solution, and
      Cd2+ (0.1-1 mM), Co2+ (1-10 mM) and Mn2+ (1-10 mM) inhibited ZT-A-induced
      aggregation. SK&F96365 (1-100 microM), a receptor operated Ca2+ channel
      antagonist, and mefenamic acid (0.1-10 microM), a non-specific divalent cation
      channel antagonist, inhibited platelet aggregation and the increase in [Ca2+]i
      induced by ZT-A. 3. Indomethacin (0.1-10 microM), a cyclo-oxygenase inhibitor,
      and SQ-29548 (0.1-10 microM), a thromboxane A2 (TXA2) receptor antagonist,
      inhibited platelet aggregation and the increase in [Ca2+]i induced by ZT-A. 4.
      Methysergide (0.01-1 microM), a 5-HT2 receptor antagonist, inhibited ZT-A-induced
      platelet aggregation but did not affect the increase in [Ca2+]i induced by ZT-A.
      5. Tetrodotoxin (1 microM), a Na+ channel blocker and chlorpheniramine (1
      microM), a H1-histamine receptor antagonist, neither affected ZT-A-induced
      platelet aggregation nor the increase in [Ca2+]i induced by ZT-A. 6. Genistein (1
      100 microM), a protein tyrosine kinase inhibitor, and staurosporine (0.01-1
      microM), a protein kinase C inhibitor, also inhibited ZT-A-induced platelet
      aggregation. 7. The present results suggest that ZT-A elicits Ca(2+)-influx from
      platelet plasma membranes. The resulting increase in [Ca2+]i subsequently
      stimulates the secondary release of TXA2 from platelets. Furthermore, the
      response to ZT-A may be associated with tyrosine phosphorylation.

PMID- 7582456
TI  - Dose-response comparisons of five lung surfactant factor (LSF) preparations in an
      animal model of adult respiratory distress syndrome (ARDS).
AB  - 1. We have examined the effects of five different lung surfactant factor (LSF)
      preparations in the rat lung lavage model. In this model repetitive lung lavage
      leads to lung injury with some similarities to adult respiratory distress
      syndrome with poor gas exchange and protein leakage into the alveolar spaces.
      These pathological sequelae can be reversed by LSF instillation soon after
      lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact:
      two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one
      Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated
      control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled
      ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate
      of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory
      pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O.
      Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8
      to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd
      reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min
      after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were
      used for statistical comparison. All LSF preparations caused a dose-dependent
      increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine
      and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2
      after administration of the highest dose. At the highest dose Exosurf exerted no
      further improvement but rather a tendency to relapse. The bovine and the
      Recombinant LSF are superior to both synthetic LSFpreparations.5. In this animal
      model and under the described specific ventilatory settings, even between bovine
      LSFpreparations there are detectable differences that are pronounced when
      compared to synthetic LSFwithout any surfactant proteins. We conclude that the
      difference between bovine and synthetic LSFpreparations can be overcome by
      addition of the surfactant protein C.

PMID- 7582457
TI  - Phosphorylation- and voltage-dependent inhibition of neuronal calcium currents by
      activation of human D2(short) dopamine receptors.
AB  - 1. Activation of human D2(s) dopamine receptors with quinpirole (10 nM) inhibits
      omega-conotoxin GVIa-sensitive, high-threshold calcium currents when expressed in
      differentiated NG108-15 cells (55% inhibition at +10 mV). This inhibition was
      made irreversible following intracellular dialysis with the non-hydrolysable
      guanosine triphosphate analogue GTP-gamma-S (100 microM), and was prevented by
      pretreatment with pertussis toxin (1 microgram ml-1 for 24 h). 2. Stimulation of
      protein kinase C with the diacylglycerol analogue, 1-oleoyl-2-acetyl-sn-glycerol
      (100 microM), also attenuated the inhibition of the sustained calcium current but
      did not affect the receptor-mediated decrease in rate of current activation.
      Similarly, okadaic acid (100 nM), a protein phosphatase 1/2A inhibitor,
      selectively occluded the inhibition of the sustained current. 3. The depression
      of calcium currents by quinpirole (10 nM) was enhanced following intracellular
      dialysis with 100 microM cyclic adenosine monophosphate (cyclic AMP, 72.8 +/-
      9.8% depression), but was not mimicked by the membrane permeant cyclic GMP
      analogue, Sp-8-bromoguanosine-3',5':cyclic monophosphorothioate (100 microM). 4.
      Inhibition of calcium currents was only partly attenuated by 100 ms depolarizing
      prepulses to +100 mV immediately preceding the test pulse. However, following
      occlusion of the sustained depression with okadaic acid (100 nM) the residual
      kinetic slowing was reversed in a voltage-dependent manner (P < 0.05). 5. Thus
      pertussis toxin-sensitive G-proteins liberated upon activation of human D2(short)
      dopamine receptors inhibited high-threshold calcium currents in two distinct
      ways. The decrease in rate of calcium current activation involved a voltage
      dependent pathway, whereas the sustained inhibition of calcium current involved,
      in part, the voltage-resistant phosphorylation by cyclic AMP-dependent protein
      kinases and subsequent dephosphorylation by protein phosphatases 1/2A.

PMID- 7582458
TI  - Evidence for a functional alpha 1A- (alpha 1C-) adrenoceptor mediating
      contraction of the rat epididymal vas deferens and an alpha 1B-adrenoceptor
      mediating contraction of the rat spleen.
AB  - 1. The alpha 1-adrenoceptor subtype mediating contraction of the rat epididymal
      vas deferens and rat spleen has been investigated by use of alpha 1-adrenoceptor
      antagonists that have shown selectivity between the different cloned receptor
      subtypes. 2. In the rat epididymal vas deferens the potency of noradrenaline and
      phenylephrine was increased in the presence of neuronal and extra-neuronal uptake
      blockers, cocaine and beta-oestradiol, but these did not alter that of
      methoxamine. The order of potency of the agonists in the presence or absence of
      uptake blockade was noradrenaline > phenylephrine > methoxamine. In the rat
      spleen the potency of these agonists was not altered in the presence of cocaine
      and beta-oestradiol, and their order of potency was the same as in the vas
      deferens. 3. The non subtype selective alpha 1-adrenoceptor antagonist prazosin
      (up to 1 x 10(-7) M) was found to antagonize contractions to noradrenaline in the
      vas deferens competitively (pA2 9.2), but only in a non competitive manner in the
      spleen. Contractions to phenylephrine in the spleen however were competitively
      antagonized by prazosin (up to 1 x 10(-7) M) with a pA2 of 9.2. This suggests
      that there is an alpha 1- and a non alpha 1-adrenoceptor response to
      noradrenaline in the rat spleen. 4. Pretreatment with chlorethylclonidine (10(-4)
      M for 30 min) did not alter the noradrenaline contractions in the vas deferens,
      but contractions to noradrenaline and phenylephrine in the spleen were shifted 30
      and 300 fold to the right of the control curve, respectively. This suggests that
      only the contractions in the spleen were mediated by alpha 1B-adrenoceptors. 5.
      The noradrenaline contractions in the vas deferens were competitively antagonized
      by WB 4101 (pA29.6), 5-methyl-urapidil (pA2 8.7), phentolamine (pA2 8.3),
      benoxathian (pA2 9.4), spiperone (pA2 7.5),indoramin (pA2 8.4) and BMY 7378 (pA2
      6.7), consistent with the affinities of these antagonists in binding studies on
      tissue alpha 1A-adrenoceptors. These values correlated best with their published
      affinities on the expressed alpha 1c-adrenoceptor clone and poorly with those at
      either the expressed alpha lb- or alpha 1d adrenoceptor clones. Therefore the
      classical alpha 1A-adrenoceptor appears to be the same as the expressed alpha lc
      adrenoceptor clone.6. The phenylephrine contractions in the spleen were
      competitively antagonized by WB 4101 (pA2 8.1),5-methyl-urapidil (pA2 7.1),
      phentolamine (pA2 7.3), benoxathian (pA2 7.4), spiperone (pA2 7.9),indoramin (pA2
      7.5) and BMY 7378 (pA2 7.4), consistent with the affinities of these antagonists
      in binding studies on tissue alB-adrenoceptors. The pA2 values correlated best
      with the published affinities of these compounds on the expressed alb
      adrenoceptor clone and poorly with those at either the expressed alpha ld- or
      alpha lc-adrenoceptor clones. Therefore the alpha lB-adrenoceptor appears to be
      the same as the expressed alpha lb-adrenoceptor clone.7. The results provide
      pharmacological evidence that the alpha1-adrenoceptor mediating noradrenaline
      contractions in the epididymal portion of the rat vas deferens is the alpha 1A
      (alpha lC) subtype and that contractions to phenylephrine in the rat spleen are
      mediated by the alpha 1B-subtype.

PMID- 7582459
TI  - Effect of enalaprilat on bradykinin and des-Arg9-bradykinin release following
      reperfusion of the ischaemic rat heart.
AB  - 1. The release of bradykinin (BK) and its metabolite, des-Arg9-bradykinin (des
      Arg9-BK), was studied following reperfusion of a globally ischaemic rat heart. 2.
      BK-like immunoreactivity increased from 13 +/- 3 (preischaemic value) to 48 +/-
      12 fmol min-1 g-1 (P < 0.05, n = 14) 30 s after reperfusion. No difference in BK
      release was found between control hearts and hearts pretreated with the
      angiotensin converting enzyme (ACE or kininase II) inhibitor, enalaprilat (50 ng
      ml-1). 3. No significant change in des-Arg9-BK-like immunoreactivity during
      reperfusion was observed in control hearts. In contrast, des-Arg9-BK-like
      immunoreactivity rose from 44 +/- 15 to 177 +/- 61 fmol min-1 g-1 (P < 0.05, n =
      7) 30 s after reperfusion in enalaprilat-treated hearts. 4. In conclusion, BK is
      released upon reperfusion of the globally ischaemic rat heart. ACE inhibitors,
      through the inhibition of kininase II, increase the formation of the active
      metabolite, des-Arg9-BK.

PMID- 7582461
TI  - Central versus peripheral site of action of the tachykinin NK1-antagonist RP
      67580 in inhibiting chemonociception.
AB  - 1. Many studies indicate an involvement of substance P in the transmission of
      nociceptive stimuli, without, however, presenting any conclusive evidence as to
      its exact site and mode of action. The present experiments tested the involvement
      of substance P in the mediation of chemical nociception using the non-peptidic
      specific tachykinin NK1-receptor antagonist, RP 67580 (2-[1-imino-2-(2
      methoxyphenyl-ethyl]-7,7diphenyl-4-perhydroiso indolone (3aR, 7aR)). 2. Mean
      arterial pressure (MAP) and intragastric pressure (IGP) were measured in
      anaesthetized rats. The reflex changes of these parameters in response to i.p. or
      s.c. injections of hydrochloric acid or capsaicin were taken to indicate
      nociception. 3. Intravenous administration of RP 67580 up to 5 mg kg-1 had little
      influence on the reflex changes in MAP or IGP in response to hydrochloric acid or
      capsaicin. In contrast, the sensitization of rats to i.p. capsaicin by
      preinjection of prostaglandin E2 was significantly reduced by 1 mg kg-1 RP 67580.
      4. Intrathecal injection of 5 micrograms RP 67580 inhibited the reflex changes of
      MAP and IGP in response to i.p. or s.c. capsaicin whereas the inactive enantiomer
      RP 68651 was ineffective. 5. The results indicate that spinal NK1-receptors are
      involved in the acute transmission of chemically induced pain, while such
      receptors in the periphery take part in the sensitization by prostaglandin E2.
      The rather minor ability of i.v. RP 67580 to inhibit the acute nociceptive reflex
      is attributed to an insufficient penetration of the blood-brain-barrier.

PMID- 7582462
TI  - Characterization of the effects of two new arginine/citrulline analogues on
      constitutive and inducible nitric oxide synthases in rat aorta.
AB  - 1. New potent inhibitors of nitric oxide synthase (NOS) may be useful in the
      treatment of septic shock, a disorder characterized by a vascular hyporeactivity
      to catecholamines caused by an overproduction of nitric oxide (NO-). We examined
      the effects of L-thiocitrulline (L-TC) and S-methyl-L-thiocitrulline (L-SMTC),
      novel NOS inhibitors, on the constitutive and inducible NOS in rat aorta and
      compared those effects with inhibition due to NG-methyl-L-arginine (L-NMA). 2.
      Phenylephrine evoked similar concentration-contraction curves in the control
      rings and in the rings treated with these different NOS inhibitors (10 microM),
      whereas 100 microM of L-NMA, L-TC or L-SMTC increased significantly, and to a
      similar extent, contractions evoked by phenylephrine in aortic rings with
      endothelium without significantly affecting the maximal responses. 3. Relaxations
      evoked by acetylcholine, adenosine triphosphate, or calcium ionophore were
      significantly inhibited in a dose-dependent manner by L-NMA, L-SMTC, or L-TC (10
      100 microM). The potencies of these inhibitors in reducing the relaxations of
      these vasodilators were not significantly different. 4. In endotoxin-treated
      preparations with endothelium, the three L-arginine analogues (10 microM)
      significantly potentiated contractile responses to phenylephrine (pEC50: 6.73 +/-
      0.12 and 7.3 +/- 0.12, 7.34 +/- 0.13, or 7.22 +/- 0.14; in the absence and the
      presence of L-NMA, L-TC, or L-SMTC respectively) and increased maximal
      contractions from 1.53 +/- 0.15 g to 1.95 +/- 0.13 g, 2.08 +/- 0.12 g, and 2.03
      +/- 0.13 g with L-NMA, L-TC, and L-SMTC respectively. A higher concentration of
      these NOS inhibitors (100 microM)further increased contractions evoked by this
      alpha1-agonist without further enhancing the maximal contractions; however,
      contractions evoked by 10 nM phenylephrine were significantly greater in the
      presence of L-SMTC or L-TC than in the presence of L-NMA (100 microM) (L-NMA: 0.4
      +/- 0.11 g; L-TC:0.78 +/- 0.14 g and L-SMTC: 0.82+/-0.17 g). The effects of these
      inhibitors on NO- synthesis induced by endotoxin were significantly reversed by
      addition of L-arginine (1 mM) but not by L-citrulline (1 mM). InLPS-treated rings
      with endothelium, all three NOS inhibitors (100 microM) shifted the concentration
      contraction curves evoked by phenylephrine significantly to the left (pEC5o: 7.19
      +/- 0.03 and 7.79 +/- 0.08,8.01 +/- 0.07, or 8.02 +_ 0.07, in the absence and the
      presence of L-NMA, L-TC, or L-SMTC, respectively)and increased significantly
      maximal contractions from 2.05 +/- 0.05 g to 2.38 +/- 0.14 g, 2.5 +/- 0.12 g, and
      2.4 +_ 0.21 g with L-NMA, L-TC, and L-SMTC, respectively. L-TC and L-SMTC were
      significantly more potent than L-NMA in potentiating contractions evoked by 10 nM
      and 30 nM phenylephrine.5. L-TC and L-SMTC produced dose-dependent increases in
      tone in LPS-treated aortic rings with and without endothelium. In LPS-treated
      rings with endothelium, L-NMA induced contractions but in preparations without
      endothelium low concentrations of L-NMA induced small contractions while high
      concentrations of this inhibitor evoked relaxations. In both preparations L-TC
      and L-SMTC were significantly more potent than L-NMA in increasing vascular
      tone.6. These results suggest that L-SMTC, L-TC and L-NMA were equipotent on
      basal and agonist stimulated NO- synthesis produced by the constitutive isoform
      of NOS, whereas the two new L-arginine analogues were more potent than L-NMA in
      inhibiting the production of NO- induced by endotoxin in rat aorta.

PMID- 7582460
TI  - Long-lasting activation of cation current by low concentration of endothelin-1 in
      mouse fibroblasts and smooth muscle cells of rabbit aorta.
AB  - 1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line
      (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels
      at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell
      recordings and monitoring the changes in intracellular free Ca2+ concentrations
      ([Ca2+]i) with a Ca2+ indicator, fluo-3. A similar type of coupling was
      investigated in freshly dispersed vascular smooth muscle cells (VSMCs) of rabbit
      thoracic aorta by use of whole-cell recordings. 2. In Ltk- cells expressing
      recombinant human ETA receptors, concentrations of ET-1 (10(-8) M, 10(-9) M)
      evoked an initial transient peak and a subsequent sustained elevation in [Ca2+]i
      whereas a lower concentration of ET-1 (10(-10) M) evoked only a sustained
      elevation of [Ca2+]i. After removal of extracellular Ca2+, ET-1 evoked only an
      initial peak without a sustained elevation of [Ca2+]i. The sustained elevation
      induced by 10(-10) M ET-1 was blocked by 300 microM mefenamic acid (a cation
      channel blocker) but not by 10 microM nifedipine (a blocker of voltage-operated
      Ca2+ channel). 3. In whole-cell recordings with Ltk- cells, a brief (3-5 min)
      application of ET-1 (10(-10) M) induced a sustained inward current at a holding
      potential of -60 mV. The current-voltage relationship revealed that the reversal
      potential of the ET-1-induced current was close to 0 mV (1.9 mV) and was not
      altered by reducing the concentration of Cl- in the bath solution, indicating
      that the current is carried by cations. The current was reversibly blocked by 300
      microM mefenamic acid, and it persisted after all cations in the bath solution
      had been replaced by Ca2+ (5 or 30 mM) and nonpermeant cation N-methyl-D
      glucamine,indicating that the ET-1-activated channel is permeable to Ca2+.
      Activation of the current was independent of membrane potential and the current
      was induced even after addition of a high concentration (10 mM) of a Ca2+
      chelator, EGTA, to the pipette solution.4. In whole-cell recordings from rabbit
      aortic VSMCs, ET-l (101-10 M) induced a sustained inward current at a holding
      potential of -60 mV. The reversal potential was - 12 mV and was not altered when
      the concentration of Cl- in the pipette solution was decreased, indicating that
      the current is carried by cations. Again activation of the current was
      independent of membrane potential and was observed even after addition of a high
      concentration (10 mM) of a Ca2+ chelator, EGTA to the pipette solution. The
      current was reversibly blocked by 300 microM mefenamic acid and was permeable to
      Ca2+,showing marked similarities to ET-1-induced cationic current in Ltk-
      cells.5. These results indicate that in Ltk- cells transfected with cDNA for
      recombinant ETA receptors andVSMCs, ETA receptors can functionally couple with a
      nonselective cation channel permeable to Ca2+.Thus the present data suggest that
      the cation channel plays an essential role in the sustained elevation of[Ca2+]i
      at low concentrations of ET-l by causing Ca2+ entry through the channel.

PMID- 7582464
TI  - The use of microdialysis for the study of drug kinetics: some methodological
      considerations illustrated with antipyrine in rat frontal cortex.
AB  - 1. The neuropharmacokinetics of antipyrine, a readily dialysable drug, in rat
      frontal cortex were studied and the effect of sampling time and contribution of
      period sampling and dialysate dead volume investigated in relation to tmax, Cmax,
      AUC and t1/2 values. 2. After i.p. administration, antipyrine (35 mg kg-1, n = 5)
      concentrations rose rapidly in rat frontal cortex (tmax, 12 min) and then
      declined exponentially tmax, Cmax, AUC and t1/2 values were determined after 2
      min dialysate sampling and compared to values obtained from simulated sampling
      times of 4, 6, 8, 10 and 20 min. 3. Antipyrine tmax and Cmax values were directly
      dependent on sampling frequency. Thus, mean 2 min sampling tmax and Cmax values
      were 63% lower and 27% higher, respectively, compared to 20 min sampling values.
      AUC and t1/2 values were unaffected. 4. Adjustment for dialysate dead volume (the
      volume of dialysate within the dialysis probe and sampling tube) reduced tmax
      values significantly but did not affect the other neuropharmacokinetic
      parameters. 5. Contribution of period sampling on neuropharmacokinetic parameters
      were investigated by comparing plots of antipyrine concentration data at midpoint
      and at endpoint of sampling time interval. Only tmax values were affected with
      values decreasing with increasing sampling time interval. 6. In conclusion,
      although microdialysis is a useful method for monitoring events at the
      extracellular level and for kinetic studies, it is important to understand its
      inherent characteristics so that data can be interpreted appropriately. Sampling
      frequency, particularly during monitoring of periods of rapid change, is very
      important since Cmax and tmax values will be significantly underestimated and
      overestimated respectively, if sampling time is longer rather than shorter. These
      considerations are particularly important in relation to microdialysis studies of
      pharmacokinetic-pharmacodynamic interrelationships and modelling.

PMID- 7582463
TI  - Attenuation by nitrosothiol NO donors of acute intestinal microvascular
      dysfunction in the rat.
AB  - 1. The effects of the nitric oxide (NO) donors, S-nitroso-glutathione (SNOG) and
      S-nitroso-N-acetyl-penicillamine (SNAP), on the acute intestinal microvascular
      dysfunction induced by NG-nitro-L-arginine methyl ester (L-NAME) in combination
      with low doses of endotoxin were investigated in the anaesthetized rat. 2.
      Administration of L-NAME (5 mg kg-1, s.c.) concurrently with E. coli
      lipopolysaccharide (LPS, 3 mg kg-1, i.v.) provoked the leakage of radiolabelled
      albumin in the ileum and colon, as a measure of microvascular damage, determined
      1 h after challenge. 3. Intravenous infusion of SNOG or SNAP (1-10 micrograms kg
      1 min-1) dose-dependently attenuated the microvascular leakage induced by L-NAME
      and LPS. 4. Infusion of the lowest doses of SNOG or SNAP (1 microgram kg-1 min-1,
      i.v.) that significantly reduced the albumin leakage, did not affect the increase
      in blood pressure in response to L-NAME in LPS-treated rats. Higher doses of SNOG
      or SNAP (5-10 micrograms kg-1 min-1, i.v.) dose-dependently reduced this increase
      in blood pressure. 5. In control studies, intravenous infusion of glutathione (10
      micrograms kg-1 min-1) or N-acetyl-penicillamine (10 micrograms kg-1 min-1) had
      no effect on microvascular leakage in the ileum and colon induced by LPS and L
      NAME. 6. Pretreatment with rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p., 4
      h before challenge), which reduced the neutrophil count in peripheral arterial
      blood, also inhibited the microvascular leakage in the ileum and colon. 7. The
      protective effects of the nitrosothiol NO donors in this model may reflect, in
      part, modulation of neutrophil interactions within the microcirculation or
      actions on endothelial cell integrity, in addition to any local vasodilator
      action.

PMID- 7582465
TI  - Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide
      synthase.
AB  - 1. The effect of acute i.v. administration of methylguanidine (MG) on mean
      arterial blood pressure (MABP) was investigated in anaesthetized male Wistar
      rats. 2. MG (1-30 mg kg-1 i.v.) produced an increase in MABP in a dose-dependent
      manner both in normal and in hexamethonium (5 mg kg-1, i.v)-treated rats. 3. L
      Arginine (30 or 150 mg kg-1, i.v.), but not its enantiomer D-arginine (30 or 150
      mg kg-1, i.v.), reversed the effect of MG on MABP in both normal and
      hexamethonium-treated rats. 4. L-Arginine (150 mg kg-1, i.v.) administered 2 min
      before MG (30 mg kg-1, i.v.) prevented the increase in MABP caused by MG in
      either normal or hexamethonium-treated rats. This effect was not observed with D
      arginine (150 mg kg-1, i.v.). 5. Thus, the rise in MABP caused by MG in the
      anaesthetized rat is due to inhibition of endothelial NO-synthase activity. We
      speculate that the rise in the plasma concentration of endogenous MG associated
      with uraemia may contribute to the hypertension seen in patients with chronic
      renal failure.

PMID- 7582467
TI  - All-or-none augmentation of Ca2+ sensitivity in alpha-toxin-permeabilized single
      smooth muscle cells from guinea-pig taenia caecum.
AB  - 1. Isolated smooth muscle cells from guinea-pig taenia caecum were permeabilized
      by use of Staphylococcus aureus alpha-toxin, and the sarcoplasmic reticulum Ca2+
      store was depleted by exposure to 0.1 microM A23187. 2. Shortening of alpha-toxin
      permeabilized single smooth muscle cells was induced by increasing free Ca2+ but
      was not induced by 0.2 microM free Ca2+. 3. Shortening of the permeabilized cells
      was caused by application of acetylcholine (ACh) with free Ca2+ concentration
      held at 0.2 microM. Permeabilized smooth muscle cells responded to 0.3 microM or
      1 microM ACh with 0.2 microM Ca2+ with maximal shortening. The concentration
      response relationship to ACh had a very steep slope and the cell shortening
      appeared to be an all-or-none response rather than a graded response, as was the
      shortening of intact cells to ACh. 4. The shortening of permeabilized cells was
      also induced by application of guanosine 5'-triphosphate (GTP) with 0.2 microM
      free Ca2+, showing an all-or-none response. The threshold concentration of GTP
      that induced an all-or-none response was between 10 microM and 30 microM. 5.
      These results suggest that Ca2+ sensitivity is augmented by stimulation of the
      muscarinic receptor or GTP-binding protein(s) in an all-or-none manner. It seems
      probable that this contributes to the all-or-none response to ACh in intact
      smooth muscle cells.

PMID- 7582466
TI  - Potentiation of P1075-induced K+ channel opening by stimulation of adenylate
      cyclase in rat isolated aorta.
AB  - 1. The effects of analogues and stimulators of cyclic AMP on the 86Rb+ efflux
      stimulating and binding properties of P1075, an opener of ATP-dependent potassium
      channels, were studied in rat aortic rings. The increase in 86Rb+ efflux
      stimulated by P1075 was taken as a qualitative measure of K+ channel opening. 2.
      Forskolin, a direct activator of adenylate cyclase, isobutylmethylxanthine
      (IBMX), a phosphodiesterase inhibitor, and dibutyryl-cyclic AMP (db-cyclic AMP),
      a membrane permeant cyclic AMP-analogue, relaxed rat aortic rings contracted by
      noradrenaline with EC50 values of 0.06, 2 and 10 microM, respectively. 3.
      Forskolin, IBMX and db-cyclic AMP produced concentration-dependent increases of
      the 86Rb+ efflux induced by P1075 (50 nM) by up to twofold with EC50 values of
      about 0.1, 1.7 and 81 microM. At these concentrations the agents had little
      effect on the basal rate of 86Rb+ efflux. 4. The 86Rb+ efflux produced by P1075
      in the presence of the cyclic AMP stimulators was inhibited by glibenclamide, a
      blocker of ATP-sensitive potassium channels. 5. IBMX (100 microM) induced a
      leftward shift of the concentration-86Rb+ efflux curve of P1075 without
      increasing the maximum. The enhancements of P1075-stimulated 86Rb+ efflux
      produced by combinations of forskolin and IBMX were either additive or less than
      additive. 6. The protein kinase A inhibitor, H-89, inhibited P1075-stimulated
      86Rb+ efflux in the presence of IBMX significantly more than in the absence of
      IBMX, suggesting that the effect of increased cyclic AMP levels is mediated by
      protein kinase A. 7. At high concentrations, forskolin and IBMX slightly
      increased basal 86Rb+ efflux and inhibited the tracer efflux induced by P1075.8.
      Binding of [3H]-P1075 to rat aortic rings was either unaffected or inhibited by
      forskolin, IBMX and db-cyclic AMP.9. This study shows that moderate stimulation
      of the cyclic AMP system potentiates the K+ channel opening effect of P1075 by
      activation of protein kinase A. The fact that binding of [3H]-P1075 remains
      unchanged or is diminished favours the hypothesis that the K'channel openers
      activate ATP-dependent K+ channels by an indirect mechanism.

PMID- 7582468
TI  - Induction of a novel form of hippocampal long-term depression by muscimol:
      involvement of GABAA but not glutamate receptors.
AB  - 1. Unlike long-term potentiation, long-term depression (LTD) in the central
      nervous system remains poorly understood. The present study was undertaken to
      investigate the role of GABAA receptors in LTD and synaptic plasticity. 2.
      Extracellular recordings were made in the CA1 pyramidal cell layer of rat
      hippocampal slices following orthodromic stimulation of Schaffer collateral
      fibres in stratum radiatum (0.01 Hz). 3. Muscimol induced a time- and
      concentration-dependent LTD of the amplitude of orthodromic potentials.
      Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 s reversed the
      LTD induced by muscimol. Muscimol also induced LTD in the absence of electrical
      stimulation. 4. Adenosine decreased the spike size in a concentration-dependent
      manner, but failed to induce LTD. 5. Alphaxalone and 5 alpha-pregnan-3 alpha-ol
      20-one at concentrations that did not have any effect themselves on the
      population spike (0.5 and 1 microM), potentiated the inhibitory effect of
      muscimol on the population spike size, including concentrations which were not
      effective by themselves. Both steroids were able to potentiate the ability of
      muscimol to induce LTD. 6. Bicuculline, 5 microM, reversed the LTD induced by
      muscimol, 10 microM. 7. The NMDA receptor antagonist (+/-)-2-amino-5
      phosphonopentanoic acid (2-AP5), the NMDA/metabotropic antagonist 2-AP3 and
      selective metabotropic antagonist L-(+)-2-amino-3-phosphonopropionic acid (L(+)
      AP3) failed to modify the LTD. Similarly, quisqualic acid and (1S, 3R)
      aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic
      receptors did not induce LTD or short-term depression, whereas kynurenic acid
      prevented the reversal of the LTD obtained at 1 Hz. 8. It is concluded that LTD
      can be induced by the selective activation of GABAA receptors. The lack of
      involvement of glutamate receptors in our protocol confirms the unique nature of
      the LTD described here. The phenomenon of GABA-induced LTD and its reversal by 1
      Hz stimulation may represent a novel type of long-lasting depression by which
      inhibitory interneurones can modulate pyramidal cell excitability in a frequency
      dependent manner.

PMID- 7582469
TI  - Effect of platelet-derived growth factor on voltage-operated calcium channels in
      rabbit isolated ear artery cells.
AB  - 1. Platelet derived growth factor (PDGF), AB and BB isoforms (100 pM) increased
      calcium channel currents measured by whole cell voltage clamp technique in single
      vascular smooth muscle cells isolated from rabbit ear arteries. 2. Tyrphostin-23
      (100 microM) a selective inhibitor of protein tyrosine kinases, reduced calcium
      channel currents. Pre-incubation with tyrphostin-23 prevented PDGF-AB induced
      increase in calcium channel currents. However, in these same cells 10 nM (+)
      202791, a dihydropyridine calcium channel agonist, did increase calcium channel
      currents. 3. Bistyrphostin (10 microM), a selective inhibitor of epidermal growth
      factor (EGF)-kinase also reduced calcium channel currents and inhibited PDGF-AB
      induced increases in calcium channel currents. 4. Genistein (100 microM) a
      selective inhibitor of tyrosine kinases, structurally unrelated to the
      tryphostins, also inhibited calcium channel currents and pre-incubation with
      genistein prevented the PDGF-AB-induced rise in calcium channel currents. 5.
      These results indicate that PDGF increases calcium channel currents in vascular
      smooth muscle. This action of PDGF probably involves a tyrosine kinase.

PMID- 7582470
TI  - Enhancement by GABA of the association rate of picrotoxin and tert
      butylbicyclophosphorothionate to the rat cloned alpha 1 beta 2 gamma 2 GABAA
      receptor subtype.
AB  - 1. We examined how gamma-aminobutyric acid (GABA) influences interaction of
      picrotoxin and tert-butylbicyclophosphorothionate (TBPS) with recombinant rat
      alpha 1 beta 2 gamma 2 GABAA receptors stably expressed in human embryonic kidney
      cells (HEK293), as monitored with changes in Cl- currents measured by the whole
      cell patch clamp technique. 2. During application of GABA (5 microM) for 15 s,
      picrotoxin and TBPS dose-dependently accelerated the decay of inward GABA-induced
      currents (a holding potential of -60 mV under a symmetrical Cl- gradient). The
      drugs, upon preincubation with the receptors, also reduced the initial current
      amplitude in a preincubation time and concentration-dependent manner. This
      indicates their interaction with both GABA-bound and resting receptors. 3. The
      half maximal inhibitory concentration for picrotoxin and TBPS at the beginning of
      a 15 s GABA (5 microM) pulse was several times greater than that obtained at the
      end of the pulse. GABA thus appears to enhance picrotoxin and TBPS potency, but
      only at concentrations leading to occupancy of both high and low affinity GABA
      sites, i.e., 5 microM. Preincubation of the receptors with the drugs in the
      presence of GABA at 200 nM, which leads to occupancy of only high affinity GABA
      sites in the alpha 1 beta 2 gamma 2 subtype, produced no appreciable change in
      potency of picrotoxin or TBPS. This indicates that they preferentially interact
      with multiliganded, but not monoliganded receptors, unlike U-93631, a novel
      ligand to the picrotoxin site, which has higher affinity to both mono- and
      multiliganded receptors than resting receptors. 4. The time-dependent decay and
      preincubation time-dependent reduction of initial amplitude of GABA-induced Cl-
      currents followed monoexponential time courses, and time constants thus obtained
      displayed a linear relationship with drug concentration. Analysis of the data
      using a kinetic model with a single drug site showed that GABA (5 microM)
      enhanced the association rate for picrotoxin and TBPS nearly 100 fold, but their
      dissociation rate only 10 fold. The dissociation rate obtained from current
      recovery from picrotoxin or TBPS block yielded nearly identical values to the
      above analysis.5. We conclude that picrotoxin and TBPS interact with both resting
      and GABA-bound receptors, but their affinity for the latter is about 10 times
      greater than that for the former, largely due to a markedly increased association
      rate to the multiliganded receptors (but not monoliganded ones). This and our
      earlier study with U-93631 improves our understanding of functional coupling
      between GABA and picrotoxin sites, which appears to be useful in characterizing
      the mode of interaction for various picrotoxin site ligands.

PMID- 7582471
TI  - Pharmacological analysis of the interaction between purinoceptor agonists and
      antagonists in the guinea-pig taenia caecum.
AB  - 1. In the absence of adenosine uptake inhibition, adenosine produced a
      concentration-dependent (threshold 30 microM) relaxation of the 5
      methylfurmethide pre-contracted guinea-pig taenia caecum. The relaxation was not
      blocked by 8-phenyltheophylline (8-PT, 3 microM) or 1,3-dipropyl, 8
      cyclopentylxanthine (DPCPX, 30 microM). 2. In the presence of the adenosine
      uptake inhibitor, dipyridamole (Dip, 3 microM), a biphasic adenosine
      concentration-effect curve was obtained (threshold 0.3 microM). The time course
      of the responses to adenosine in the absence of Dip was similar to that of the
      second phase responses in the presence of Dip and occurred over the same
      adenosine concentration-range. 5'-(N-ethyl) carboxamido-adenosine (NECA)
      concentration-effect curves (in the absence of Dip) were also biphasic. Only the
      first phases of the concentration-effect curves obtained with NECA and adenosine
      (plus Dip) were inhibited by 8-PT. The pA2 values for 8-PT of 6.7 and 7.0 versus
      adenosine and NECA, respectively, were consistent with actions at P1
      purinoceptors. There was a trend towards an increase in the upper asymptote of
      the first phase of the NECA curve in the presence of increasing concentrations of
      8-PT. The A1-purinoceptor selective antagonist, DPCPX, also blocked only the
      first phase of the NECA concentration-effect curve and produced a significant
      increase in the upper asymptote. The pA2 value (6.8) obtained was consistent with
      activation of A2-subtype P1-purinoceptors by the low concentrations of NECA. 3.
      There was no correlation between A1-purinoceptor affinity and the propensity to
      cause the increase in the upper asymptote of the first phase of the NECA
      concentration-effect curves amongst a series of 9-methyl adenine analogues,
      suggesting that the amplification was not due to inhibition of an underlying A1
      purinoceptor-mediated contractile response.4. DPCPX (10 microM) produced a
      significant increase in the upper asymptote of the NECA concentration effect
      curve, but had no effect on isoprenaline curves whereas the phosphodiesterase
      inhibitor Ro20-1724 (30 microM) produced a significant increase in the upper
      asymptote of both NECA and isoprenaline concentration-effect curves. Therefore
      the amplification of the first phase responses by DPCPX did not appear to be due
      to phosphodiesterase inhibition.5. It was not possible to conclude whether second
      phase responses to adenosine and NECA were mediated by intracellular or
      extracellular sites of action. However, if intracellular sites of action were
      involved then adenosine did not apparently gain access by the Dip-sensitive
      uptake system.

PMID- 7582475
TI  - Acute and chronic cardiac and regional haemodynamic effects of the novel
      bradycardic agent, S16257, in conscious rats.
AB  - 1. We carried out experiments to assess the cardiac and regional haemodynamic
      effects of single or repeated injections of the novel bradycardic agent. S16257,
      (7,8-dimethoxy 3-[3-([(IS)-(4,5-dimethoxybenzocyclobutan-1-
      yl)methyl]methylamino)propyl] 1,3,4,5-tetrahydro-2H-benzapin 2-one), in conscious
      rats. 2. In the first experiment, male Long Evans rats were chronically
      instrumented for the measurement of cardiac or regional haemodynamics (n = 9 in
      each group), and, on separate experimental days, were randomized to receive i.v.
      bolus injections of vehicle (5% dextrose) or S16257 at a dose of 1 mg kg-1. 3. In
      animals instrumented for the measurement of cardiac haemodynamics (n = 9),
      following injection of vehicle, there were no immediate changes, and 7-8 h later
      there were slight reductions in heart rate and mean arterial blood pressure only.
      Injection of S16257 caused an immediate, transient, pressor effect but thereafter
      there were reductions in heart rate, mean arterial blood pressure, cardiac index
      and total peripheral conductance, together with increases in stroke index and
      peak aortic flow. The integrated decreases in heart rate, mean arterial blood
      pressure, cardiac index and total peripheral conductance and increases in stroke
      index, peak aortic flow, dF/dtmax and central venous pressure following S16257
      were all significantly greater than the changes after vehicle injection. After
      injection of S16257, the fall in heart rate and fall in cardiac index were not
      linearly related. 4. In animals instrumented for the measurement of regional
      haemodynamics (n = 9). the bradycardic effect of i.v. S16257 was accompanied by
      reductions in renal, mesenteric and hindquarters blood flows and vascular
      conductances that were greater than the changes seen following injection of
      vehicle, but only for the first 1 h. Considering animals instrumented for the
      measurement of cardiac and regional haemodynamics together, the bradycardic
      effect of S16257 was greater the higher the resting heart rate.5. In the second
      experiment, animals chronically instrumented for the measurement of cardiac or
      regional haemodynamics (n = 9 in each group) were given s.c. injections of S16257
      (1 mg kg-1) on four consecutive days. The general patterns of change in cardiac
      and regional haemodynamics following s.c.injection of S16257 were as described
      above for i.v. injection, although the rates of onset of effects were slower. The
      bradycardic effect of S16257 was less on the first, than on the subsequent, three
      days.6 Overall, these results indicate that the bradycardic action of S16257 is
      not associated with any signsof negative inotropic action. Only the initial
      depressor effect of i.v. S16257 is associated with reductions in renal,
      mesenteric and hindquarters flow and vascular conductance significantly greater
      than those seen after vehicle injection. With repeated s.c. injection of S16257,
      there are no signs of desensitization to its bradycardic actions, nor impairment
      of regional perfusion. If these results extrapolate to the clinical setting, it
      seems likely that S16257 will have beneficial bradycardic effects, with no
      concurrent undesirable actions on other aspects of cardiovascular function.

PMID- 7582472
TI  - Prevention by blockade of angiotensin subtype1-receptors of the development of
      genetic hypertension but not its heritability.
AB  - 1. We determined whether early inhibition of angiotensin II subtype1 (AT1)
      receptors by the newly synthesized nonpeptidic antagonist, A-81988, can attenuate
      the development of hypertension in spontaneously hypertensive rats (SHR) and if
      the altered blood pressure phenotype can be passed on to the subsequent
      generation, not exposed to the antagonist. 2. Pairs of SHR were mated while
      drinking tap water or A-81988 in tap water, and the progeny was maintained on the
      parental regimen until 14 weeks of age. At this stage, A-81988-treated rats
      showed lower systolic blood pressure and body weight values (136 +/- 5 versus 185
      +/- 4 mmHg and 247 +/- 4 versus 283 +/- 4 g in controls, P < 0.01); while heart
      rate was similar. In addition, mean blood pressure was reduced (101 +/- 7 versus
      170 +/- 7 mmHg in controls, P < 0.01), and the pressor responses to intravenous
      or intracerebroventricular angiotensin II were inhibited by 27 and 59%,
      respectively. Heart/body weight ratio was smaller in A-81988-treated rats (3.2 +/
      0.1 versus 3.8 +/- 0.1 in controls, P < 0.01). 3. The antihypertensive and
      antihypertrophic effect of A-81988 persisted in rats removed from therapy for 7
      weeks (systolic blood pressure: 173 +/- 4 versus 220 +/- 4 mmHg, heart/body
      weight ratio: 3.4 +/- 0.1 versus 4.1 +/- 0.1 in controls at 21 weeks of age, P <
      0.01 for both comparisons), whereas the cardiovascular hypertensive phenotype was
      fully expressed in the subsequent generation that was maintained without
      treatment. 4. These results indicate that chronic blockade of angiotensin AT1
      receptors attenuates the development of hypertension in SHR but it does not
      prevent the transmission of hypertension to the following generation. Thus,
      heritability of the SHR's hypertensive trait is not affected by pharmacological
      manipulation of the cardiovascular phenotype.

PMID- 7582473
TI  - Additive effect of ADP and CGRP in modulation of the acetylcholine receptor
      channel in Xenopus embryonic myocytes.
AB  - 1. We have previously shown that the activation of either protein kinase A (PKA)
      or protein kinase C (PKC) enhanced the responses of muscle membrane to
      acetylcholine (ACh) by increasing the mean open time of embryonic-type ACh
      channels in Xenopus cultured myocytes. In the present study, we further
      investigated the interaction between these two kinases in the modulation of ACh
      channels by using the receptor ligands, adenosine diphosphate (ADP) and
      calcitonin gene-related peptide (CGRP) which selectively activate PKC and PKA,
      respectively. 2. ADP concentration-dependently increased the mean open time of
      embryonic-type ACh channels and 0.3 mM ADP is sufficient to achieve the maximal
      potentiating effect. alpha, beta-Methylene ATP and PMA (phorbol 12-myristate 13
      acetate) but not adenosine, AMP, dibutyryl cyclic GMP have similar potentiating
      action. 3. Suramin (0.3 mM) pretreatment abolished the potentiating effect of ADP
      but left that of PMA unchanged. 4. CGRP increased the mean open time of embryonic
      type ACh channels in a concentration-dependent manner and 1 microM CGRP produced
      the maximal effect. 5. The maximal effects of both ADP (0.3 mM) and CGRP (1
      microM) in the prolongation of mean open time of ACh channels were additive. 6.
      These results suggest that the modulation of embryonic-type ACh channels by the
      endogenously released ligands via the activation of PKA and PKC is additive and
      possibly different sites of ACh channels may be involved in the potentiation
      effect of either PKC or PKA.

PMID- 7582476
TI  - Effect of swimming on vascular reactivity to phenylephrine and KC1 in male rats.
AB  - 1. The present study aimed to examine whether there is any change in vascular
      responsiveness to phenylephrine and KC1 during exercise, and whether the vascular
      endothelium plays a role in these changes. 2. Adult male rats were subjected to a
      swimming schedule every day for 5-6 weeks. Studies were performed in vitro on
      thoracic aortae. 3. Maximum contractile response to phenylephrine of endothelium
      intact thoracic aortic rings (passive tension 1.0 g) obtained from swimming rats
      (1.2 +/- 0.2 g, n = 8) was lower than of sedentary control rats (2.1 +/- 0.2 g, n
      = 8). When the endothelium was removed, however, the dose-response curves of both
      groups of rats were shifted to the left with an increase in maximum responses and
      they were no longer significantly different (max. tension, swimming rats: 3.2 +/-
      0.3 g, n = 6, control rats: 3.4 +/- 0.4 g, n = 5). 4. Indomethacin did not
      significantly alter the dose-response curves. A similar effect to that obtained
      by removal of the endothelium was observed when methylene blue and indomethacin
      were both added. 5. Passive tension in the range of 2.5-3.0 g, caused a
      significant increase in active tension developed to phenylephrine (1 microM for
      endothelium-intact and 0.1 microM for endothelium-denuded) of thoracic aortic
      rings of both swimming and sedentary control rats compared to their corresponding
      groups when using passive tension of 1.0-1.5 g. 6. The reduction in responses to
      phenylephrine of endothelium-intact thoracic aortic rings of swimming rats
      persisted with the use of a passive tension of 3.0 g. The presence of 300 microM
      N0-nitro-L-arginine (LNOARG)caused a significant leftward shift of the curve with
      an increase in maximum responses when a passive tension of either 1.0 or 3.0 g
      was applied to the rings. However, for the rings with a passive tension of 1.0 g,
      L-NOARG caused a smaller increase in maximal contractile responses to
      phenylephrine of the rings of sedentary controls than those of swimming rats.7.
      There was no difference in the dose-response curves to depolarizing
      concentrations of KCl (20, 40, 80 and 120 mM) of endothelium-intact thoracic
      aortic rings from swimming and sedentary control rats.When the endothelium was
      removed, however, the dose-response curves of both groups of animals were shifted
      to the left with an increase in maximum responses. Moreover, the responses to KCl
      of endothelium-denuded thoracic aortic rings of swimming rats were greater than
      those of sedentary control rats.8. These results suggest that there were changes
      in vascular responsiveness to phenylephrine and KCl during exercise. The fall in
      sensitivity to phenylephrine with no change in KCl responses, and the increase in
      maximum responses to phenylephrine in the presence of L-NOARG in endothelium
      intact aortae (passive tension 1.0 g) from swimming rats, were due to an increase
      in spontaneous release and upregulation of phenylephrine-stimulated release of
      EDRF/NO, and may not be a consequence of an increase in prostaglandins or a
      decrease in the production of endothelial constrictors by vascular endothelium.
      EDRF/NO may play an important role in modulating local vasodilatation.

PMID- 7582474
TI  - Contractile actions of thrombin receptor-derived polypeptides in human umbilical
      and placental vasculature: evidence for distinct receptor systems.
AB  - 1. We studied the structure-activity profiles of four thrombin receptor-derived
      polypeptides (TRPs) (P5, SFLLR; P5-NH2, SFLLR-NH2; P7, SFLLRNP; P7-NH2, SFLLRN)
      in contractile human placental artery (PA), umbilical artery (UA) and umbilical
      vein (UV) preparations and in a human platelet aggregation assay. 2. The
      contractile actions of the TRPs in the two arterial preparations were endothelium
      independent, whereas in the UV tissue a contractile response was observed only in
      an endothelium-denuded preparation; no endothelium-mediated relaxation responses
      were observed in any of the vascular preparations. 3. In the three vascular
      preparations, the contractile responses required extracellular calcium and were
      attenuated by the tyrosine kinase inhibitor, genistein. 4. The relative
      contractile orders of potencies of the TRPs in the three vascular preparations
      were distinct from each other (PA: P7-NH2 > P7 > P5-NH2 > P5; UA: P7-NH2 > or =
      P5-NH2 approximately = P7 > > P5; UV: P5-NH2 > > P7-NH2 = P7 > > P5) and these
      were in turn distinct from the potency order observed in the platelet aggregation
      assay (P5-NH2 > or = P7-NH2 > P7 > > P5). 5. Despite the markedly dissimilar TRP
      potency orders in the placental artery and umbilical vein preparations, the cDNA
      sequences for the thrombin receptor obtained by polymerase chain reaction cloning
      of cDNA from the two tissue sources were identical. 6. We conclude that the four
      tissues studied possess functionally distinct thrombin receptor systems that
      interact in a distinct way with agonist peptides. In view of the identity of the
      thrombin receptor cDNA in the two tissues displaying the most dissimilar
      structure-activity profiles, we suggest that in different tissues, differences in
      post-translational receptor processing or differences in receptor-effector
      coupling interactions may result in unique thrombin receptor systems that can
      display distinct structure-activity profiles.

PMID- 7582477
TI  - Protein kinase C in rat brain cortex and hippocampus: effect of repeated
      administration of fluoxetine and desipramine.
AB  - 1. Recent evidence indicates that changes in the activity of cyclic AMP-dependent
      protein kinase may be involved in neuroadaptive mechanisms after chronic
      treatment with antidepressants. The aim of this study was to investigate the
      effect of repeated administration of fluoxetine (FL) and desipramine (DMI) on the
      distribution and activity of protein kinase C (PKC) in subcellular fractions of
      rat cortex (Cx) and hippocampus (Hc) under basal conditions and in response to a
      single in vivo administration of 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane (DOI). 2. Rats were treated for 21 days with FL (5 mg
      kg-1 day-1, i.p.) or DMI (10 mg kg-1 day-1, i.p.). DOI was injected to groups of
      rats receiving repeated doses of antidepressants or to control rats 1 h before ex
      vivo PKC assay. Distribution of PKC was determined by [3H]-phorbol-12,13
      dibutyrate ([3H]-PDBu) binding and PKC activity by the Amersham enzyme assay
      system. 3. Autoradiography of tissue sections revealed decreased [3H]-PDBu
      binding in CA1 region of hippocampus (by 18%) and paraventricular thalamic
      nucleus (by 28%) of rats after repeated administration of FL. 4. In vitro
      exposure of brain sections to 50 microM FL resulted in significant decreases (by
      23-32%) of [3H]-PDBu binding in six out of seven regions examined; exposure to
      100 microM FL reduced [3H]-PDBu binding (by 36-52%) in all regions. In contrast,
      exposure of brain sections to 100 microM DMI failed to alter specific [3H]-PDBu
      binding in brain sections. 5. The activity of PKC in subcellular fractions of Cx
      and Hc was significantly (by 40-50%) decreased in rats given repeated doses of FL
      or DMI. A single administration of either drug was without effect.6. A single in
      vivo administration of DOI to control rats resulted in reduced PKC activity (by
      30-40%)in the particulate fraction of both Cx and Hc. This response to DOI was
      similar in DMI-treated rats but was not seen in rats given repeated doses of FL.
      A single administration of DOI to animals given repeated doses of FL resulted in
      PKC activities higher than those seen in rats treated with FL alone.7. The
      results indicate that repeated administration of FL and DMI produced similar
      changes in basal PKC activity but differentially affected the PKC response to the
      5-HT2A/2c receptor agonist, DOI. The effect on basal PKC activity may result from
      a post-receptor action of antidepressants; the alteration of PKC response to DOI
      after fluoxetine could be due to receptor-mediated desensitization of the
      signalling system.

PMID- 7582478
TI  - Reduction of inflammation and pyrexia in the rat by oral administration of SDZ
      224-015, an inhibitor of the interleukin-1 beta converting enzyme.
AB  - 1. The aim of this study was to determine whether a synthetic inhibitor of the
      interleukin-1 beta converting enzyme (ICE) displays oral activity in models of
      inflammation. 2. To this end, the ICE inhibitor, SDZ 224-015, was examined in rat
      paw oedema, pyrexia and nociception tests. 3. SDZ 224-015 (0.3-300 micrograms kg
      1) potently reduced carrageenin-induced paw oedema, with an oral ED50 of
      approximately 25 micrograms kg-1. This effect was independent of endogenous
      glucocorticoid, as shown by retention of activity upon adrenalectomy. 4. Pyrexia
      induced by lipopolysaccharide (0.1 mg kg-1 s.c.) or by interleukin-1 beta (100 ng
      i.v.) was also reduced, over a similar dose-range to oedema (oral ED50s 11
      micrograms kg-1 and 4 micrograms kg-1 respectively). 5. SDZ 224-015 (0.2-5 mg kg
      1, p.o.) displayed analgesic activity in the Randall-Selitto yeast-inflamed paw
      pressure test, significant at a dose of 1 mg kg-1, p.o. 6. Thus, SDZ 224-015 has
      potent oral activity in several acute models for inflammation, suggesting that
      ICE inhibitors may constitute a novel type of anti-inflammatory agent.

PMID- 7582479
TI  - The involvement of ATP-sensitive potassium channels in beta-adrenoceptor-mediated
      vasorelaxation in the rat isolated mesenteric arterial bed.
AB  - 1. We have used the isolated buffer-perfused superior mesenteric arterial bed of
      the rat to assess the involvement of ATP-sensitive potassium (KATP) channels in
      the vasorelaxant responses to beta-adrenoceptor agonists. 2. The vasorelaxant
      potencies of the non-selective beta-adrenoceptor agonist, isoprenaline, the beta
      1-adrenoceptor agonist, dobutamine and the beta 2-adrenoceptor agonist,
      terbutaline were all significantly (P < 0.05) reduced (isoprenaline, ED50 = 265
      +/- 31 pmol v. 1.05 +/- 0.42 nmol; dobutamine, ED50 = 294 +/- 67 pmol v. 497 +/-
      115 pmol; terbutaline, ED50 = 157 +/- 26 nmol v. 452 +/- 120 nmol) in the
      presence of the KATP-channel blocker, glibenclamide. 3. The presence of
      glibenclamide only weakly influenced the vasorelaxant properties of salbutamol, a
      beta 2-adrenoceptor agonist, while those of verapamil, a beta-adrenoceptor
      independent vasorelaxant, were unaffected. 4. In radioligand binding experiments,
      glibenclamide (1 nM-100 microM) did not displace any specific [3H]
      dihydroalprenolol binding from rat beta-adrenoceptors. Therefore, glibenclamide
      does not bind to beta-adrenoceptors at the concentration used in the present
      investigation. 5. Vasorelaxant responses to dibutyryl cyclic AMP, the cell
      permeable analogue of cyclic AMP, were also unaffected by glibenclamide,
      indicating that the coupling of beta-adrenoceptors to KATP-channels occurs
      independently of the elevation of intracellular cyclic AMP. 6. We have shown that
      a significant element of the vasorelaxant responses to both beta 1- and beta 2
      adrenoceptor activation involves the opening of KATP-channels. In conclusion,
      KATP-channels may play a physiological role in beta-adrenoceptor-mediated
      vasodilatation.

PMID- 7582481
TI  - The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B)
      receptor gene products: comparison with 5-HT2A and 5-HT2C receptors.
AB  - 1. Full length clones of the human 5-HT2B receptor were isolated from human
      liver, kidney and pancreas. The cloned human 5-HT2B receptors had a high degree
      of homology (approximately 80%) with the rat and mouse 5-HT2B receptors. 2. PCR
      amplification was used to determine the tissue distribution of human 5-HT2B
      receptor mRNA. mRNA encoding the 5-HT2B receptor was expressed with greatest
      abundance in human liver and kidney. Lower levels of expression were detected in
      cerebral cortex, whole brain, pancreas and spleen. Expression was not detected in
      heart. 3. Northern blot analysis confirmed the presence of 5-HT2B receptor mRNA
      (a 2.4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized
      band of hybridization was detected in liver and kidney. This raises the
      possibility of a splice variant of the receptor or the presence of an additional
      homologous receptor. 4. The human 5-HT2B receptor was expressed in Cos-7 cells
      and its ligand binding characteristics were compared to similarly expressed human
      5-HT2A and 5-HT2C receptors. The ligand specificity of the human 5-HT2B receptor
      (5-HT > ritanserin > SB 204741 > spiperone) was distinct from that of the human 5
      HT2A (ritanserin > spiperone > 5-HT > SB 204741) and 5-HT2C (ritanserin > 5-HT >
      spiperone = SB 204741) receptors. On the basis of a higher affinity for
      ketanserin and a lower affinity for yohimbine the human 5-HT2B receptor also
      appeared to differ from the rat 5-HT2B receptor. 5. These findings confirm the
      sequence of the human 5-HT2B receptor and they demonstrate that the receptor has
      a widespread tissue distribution. In addition, these data suggest that there are
      differences in ligand affinities between different species homologues of the
      receptor. Finally, the finding of two distinct bands on the Northern blots of
      liver and kidney raises the possibility of splice variants or subtypes of 5-HT2B
      receptors, within these tissues.

PMID- 7582483
TI  - Contribution of P2-purinoceptors to neurogenic contraction of rat urinary bladder
      smooth muscle.
AB  - 1. The contribution of P2-purinoceptors to neurogenic contraction was
      investigated in rat urinary bladder smooth muscle by measurement of isotonic
      tension. 2. Contraction of rat urinary bladder smooth muscle induced by
      electrical stimulation was decreased to 84.19 +/- 3.90% of the control (n = 16)
      in the presence of atropine (1 microM), which was further decreased to 38.80 +/-
      2.75% of the control (n = 49) in the presence of both atropine and 10 microM
      alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-Me ATP). 3. The
      contractile response induced by electrical stimulation in the presence of
      atropine and alpha, beta-Me ATP was decreased to 27.81 +/- 4.07% (n = 23) and
      26.63 +/- 5.01% (n = 15) of the control, by the addition of 100 microM cibacron
      blue 3GA and 100 microM suramin, respectively. The application of 100 microM
      adenosine 5'-o-2-thiodiphosphate (ADP beta S) in the presence of atropine and
      alpha, beta-Me ATP decreased the contractile response induced by electrical
      stimulations to 17.15 +/- 3.71% (n = 15) of the control. 4. Pretreatment of
      muscle strips with 100 microM ADP beta S significantly reduced the response to
      either 200 microM alpha, beta-methylene adenosine 5'-diphosphate or 200 microM
      ADP beta S. 5. Uridine 5'-triphosphate (100 microM to 1 mM) concentration
      dependently contracted muscle strips, and this contraction was significantly
      antagonized by desensitization of P2-receptors with alpha, beta-Me ATP (10
      microM), and completely antagonized by pretreatment of muscle strips with both
      alpha, beta-Me ATP and ADP beta S (100 microM). 6. Di(adenosine-5')
      tetraphosphate (30 and 100 microM) contracted muscle strips, whereas it failed to
      contract after desensitization of P2-receptors.7. It is suggested that about 20%
      of the neurogenic contraction of rat urinary bladder smooth muscle is mediated
      via ADP beta S-sensitive purinoceptors.

PMID- 7582480
TI  - Regional haemodynamic effects of mu-, delta-, and kappa-opioid agonists
      microinjected into the hypothalamic paraventricular nuclei of conscious,
      unrestrained rats.
AB  - 1. The cardiovascular effects of bilateral injection into the hypothalamic
      paraventricular nuclei of selective mu-, delta-, and kappa-opioid receptor
      agonists were investigated in conscious, unrestrained Wistar Kyoto rats,
      chronically instrumented with pulsed Doppler flow probes for measurement of
      regional haemodynamics. 2. The selective mu-agonist [D
      Ala2,MePhe4,Gly5ol]enkephalin (DAMGO), injected bilaterally into the hypothalamic
      paraventricular nuclei (0.01-1.0 nmol), caused increases in blood pressure,
      tachycardias, vasoconstriction in renal and superior mesenteric vascular beds and
      substantial vasodilatation in the hindquarter vascular bed. 3. The administration
      of increasing doses (0.01-5.0 nmol) of the selective delta-agonist [D
      Phe2,5]enkephalin (DPDPE) or the selective kappa-agonist, U50488H into the
      paraventricular nuclei (PVN) had no significant effect on blood pressure, heart
      rate, or regional haemodynamics. 4. Together, the present results are further
      evidence of a role for opioid peptides, especially acting at mu-receptors in the
      PVN, in the central regulation of the cardiovascular system, whereas a role for
      opioid peptides, acting at delta- and kappa-receptors in the PVN, seems less
      obvious from the present results.

PMID- 7582482
TI  - Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during
      ischaemia and reperfusion.
AB  - 1. Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of
      mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085
      DV), were studied for their ability to modify the release of nitrite and the
      coronary flow in perfusates collected from isolated, normally perfused hearts of
      guinea-pigs and from hearts subjected to regional ischaemia and reperfusion. 2.
      In guinea-pig normally perfused hearts, both defibrotide (DFT) and its fraction,
      P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a
      concentration-dependent fashion. At the highest concentration studied (10(-6) M),
      P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary
      flow was observed. 3. The increase in nitrite in perfusates and the increase in
      coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by
      NG-monomethyl-L-arginine (L-NMMA, 10(-4) M), an inhibitor of nitric oxide
      synthase (NOS). 4. The endothelium-dependent vasodilator, acetylcholine (ACh),
      enhances the formation of nitrite and the coronary flow. Both the increase in
      coronary flow and in the formation of nitrite were significantly reduced by L
      NMMA (10(-4) M). 5. In guinea-pig hearts subjected to ischaemia and reperfusion,
      the effect of both compounds in increasing the amount of nitrite in perfusates
      was more evident and more pronounced with P.O. 085 DV. 6. Reperfusion-induced
      arrhythmias were significantly reduced by both compounds to the extent of
      complete protection afforded by compound P.O. 085 DV. 7. The cardioprotective and
      antiarrhythmic effects of DFT and P.O. 085 DV are discussed.

PMID- 7582487
TI  - Characterization of the receptors and mechanisms involved in the cardiovascular
      actions of sCCK-8 in the pithed rat.
AB  - 1. The cardiovascular actions of cholecystokinin and related peptides were
      investigated in the pithed rat. The receptors and the mechanisms involved in
      these experiments were characterized. 2. Sulphated cholecystokinin octapeptide
      (sCCK-8, 0.1-100 nmol kg-1, i.v.) elicited a dose-dependent bradycardia and
      increase in mean arterial blood pressure. Neither gastrin-17 nor pentagastrin had
      any effect at concentrations up to 100 nmol kg-1. 3. Both the pressor response
      and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor
      antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1). The
      selective CCKB receptor antagonists, CI-988 (1 mumol kg-1) and L-365,260 (15
      mumol kg-1) did not inhibit the effects of sCCK-8. 4. The pressor response
      induced with sCCK-8 was reduced by treatment with either phentolamine (3 mumol kg
      1) or guanethidine (2 mumol kg-1) and was unaffected by treatment with
      propranolol, atropine or hexamethonium. The pressor response also persisted
      following bilateral adrenalectomy. 5. The bradycardia induced with sCCK-8 was
      unaffected by treatment with phentolamine, propranolol, guanethidine, atropine,
      hexamethonium or bilateral adrenalectomy. 6. The tetrapeptide of cholecystokinin
      (CCK-4) elicited a dose-dependent pressor response but did not induce
      bradycardia. The pressor response was unaffected by devazepide (50 nmol kg-1), L
      365260 (15 mumol kg-1) or phentolamine (3 mumol kg-1). 7. In the pithed rat, sCCK
      8 acted via CCKA receptors to increase arterial blood pressure indirectly, at
      least in part, through activation of alpha-adrenoceptors. The observed
      bradycardia was also mediated byCCKA receptors but possibly through a direct
      action on the heart.

PMID- 7582485
TI  - Contribution of P1-(A2b subtype) and P2-purinoceptors to the control of vascular
      tone in the rat isolated mesenteric arterial bed.
AB  - 1. The direct vascular effects of adenosine and ATP were compared in the isolated
      and perfused mesenteric arterial bed of the rat. The actions of analogues of
      adenosine and ATP were also examined. 2. In preparations at basal tone, adenosine
      lacked vasoconstrictor actions, while ATP elicited dose-dependent vasoconstrictor
      responses. When the tone of preparations was raised by adding methoxamine to the
      perfusate, adenosine and its stable analogue, 2-chloroadenosine (2-CADO) elicited
      dose-dependent vasodilation. The A2 adenosine receptor agonist, 5'-N
      ethylcarboxamidoadenosine (NECA) was active at lower doses than adenosine, while
      the A2a-selective agonist, CGS 21680 and the selective A1 agonist, N6
      cyclopentyladenosine (CPA) failed to induce vasodilatation. ATP and its analogue,
      2-methylthio ATP, elicited dose-dependent vasodilatation at doses 400 fold lower
      than adenosine. 3. Vasodilator responses to adenosine and 2-CADO were sensitive
      to antagonism by 1 microM 8-sulphophenyltheophylline (8-SPT) and were unaffected
      by inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester
      (L-NAME). In contrast, vasodilator responses to ATP were not sensitive to
      antagonism by 8-SPT and were almost abolished by L-NAME treatment. 4. These
      results indicate that in the rat mesenteric arterial bed, while both adenosine
      and ATP participate in the purinergic control of vascular tone, adenosine appears
      to be a weaker vasodilator than ATP and lacks vasoconstrictor action. A2b
      adenosine receptors account for the adenosine-induced vasodilatation which is
      independent of the production of nitric oxide.

PMID- 7582484
TI  - Mechanism of bradykinin-induced plasma extravasation in the rat knee joint.
AB  - 1. We have investigated the mechanism of bradykinin (BK)-induced plasma
      extravasation into the knee joint of the anaesthetized rat. Accumulation of
      [125I]-human serum albumin within the synovial cavity was used as a marker of
      increased vascular permeability. 2. Perfusion with BK (1 microM) produced
      significant plasma extravasation into the knee which was inhibited by co
      perfusion of the selective bradykinin B2 receptor antagonist D-Arg-[Hyp3,Thi5,D
      Tic7,Oic8]-bradykinin (Hoe 140, 200 nM). 3. The bradykinin B1 receptor agonist,
      [des-Arg9]-BK (up to 100 mM), did not induce plasma extravasation into the knee
      joint, over this time period. 4. Chemical sympathectomy by chronically
      administered 6-hydroxydopamine (6-OHDA) did not inhibit bradykinin-induced plasma
      extravasation. Acute intra-articular perfusion with 6-OHDA (to stimulate
      transmitter release from sympathetic nerve terminals) at concentrations up to 50
      mM did not induce significant plasma extravasation. Intra-articular perfusion of
      100 mM 6-OHDA induced significant plasma extravasation but produced severe
      systemic toxicity. 5. The selective neurokinin1 (NK1) receptor antagonist,
      RP67580 (230 nmol kg-1), or receptor antagonists for the mast cell products
      histamine and 5-hydroxytryptamine did not significantly inhibit BK-induced plasma
      extravasation. 6. Co-perfusion of the NO synthase inhibitor, NG-nitro-L-arginine
      methyl ester (L-NAME) (1 mM) did not significantly inhibit the response to BK.
      133Xe clearance from L-NAME (1 mM)-injected joints was significantly (P < 0.05)
      reduced compared to D-NAME injected joints, suggesting a reduction in blood flow
      as a result of decreased basal NO production. Systemic administration of L-NAME
      at doses sufficient to produce significant and sustained elevation of blood
      pressure (5 or 30 mg kg-1, i.v. 15 min prior to BK perfusion) also failed to
      significantly inhibit the BK-induced response.7 We conclude that, in normal
      joints, BK induces plasma extravasation by acting on bradykinin B2 receptors and
      that this response is not dependent on secondary release of mediators from
      sympathetic nerve terminals, sensory nerves, mast cells or on generation of NO.

PMID- 7582489
TI  - Elevation of plasma noradrenaline levels in urethane-anaesthetized rats by
      activation of central prostanoid EP3 receptors.
AB  - 1. We studied the effects of intracerebroventricular (i.c.v.) administration of
      prostaglandin E2 (PGE2) and its receptor subtype ligands on plasma levels of
      catecholamines in urethane-anaesthetized rats. 2. Administration of PGE2 (0.15,
      0.3 and 1.5 nmol per animal, i.c.v.) dose-dependently elevated plasma levels of
      noradrenaline (NA), while the levels of adrenaline were not affected. 3.
      Administration of sulprostone (EP3/EP1 agonist) and misoprostol (EP3/EP2 agonist)
      effectively elevated plasma NA levels in a dose-dependent manner (0.1, 0.3, and
      1.0 nmol per animal). Butaprost (EP2 agonist) (0.3, 1.0 and 3.0 nmol per animal)
      was without effect. 17-Phenyl-omega-trinor PGE2 (EP1/EP3 agonist) effectively
      elevated plasma NA levels only at its highest dose (1.0 nmol per animal), but
      this elevation was not attenuated by pretreatment with SC-19220 (selective EP1
      antagonist) (20 nmol per animal, i.c.v.). 4. The potency of these test agents in
      elevating plasma levels of NA was as follows; misoprostol > sulprostone > PGE2 >
      > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that
      activation of central prostanoid EP3-receptors induces central sympathetic
      outflow in rats.

PMID- 7582488
TI  - No evidence for a role of muscarinic M2 receptors in functional antagonism in
      bovine trachea.
AB  - 1. The functional antagonism between methacholine- or histamine-induced
      contraction and beta-adrenoceptor-mediated relaxation was evaluated in bovine
      tracheal smooth muscle in vitro. In addition, the putative contribution of
      muscarinic M2 receptors mediating inhibition of beta-adrenoceptor-induced
      biochemical responses to this functional antagonism was investigated with the
      selective muscarinic antagonists, pirenzepine (M1 over M2), AF-DX 116 and
      gallamine (M2 over M3), and hexahydrosiladiphenidol (M3 over M2). 2. By use of
      isotonic tension measurement, contractions were induced with various
      concentrations of methacholine or histamine, and isoprenaline concentration
      relaxation curves were obtained in the absence or presence of the muscarinic
      antagonists. Antagonist concentrations were chosen so as to produce selective
      blockade of M2 receptors (AF-DX 116 0.1 microM, gallamine 30 microM), or half
      maximal blockade of M3 receptors (pirenzepine 0.1 microM, AF-DX 116 0.5 microM,
      hexahydrosiladiphenidol 0.03 microM). Since these latter antagonist
      concentrations mimicked KB values towards bovine tracheal smooth muscle M3
      receptors, antagonist-induced decreases in contractile tone were compensated for
      by doubling the agonist concentration. 3. It was found that isoprenaline-induced
      relaxation of bovine tracheal smooth muscle preparations was dependent on the
      nature and the concentration of the contractile agonist used. Thus, isoprenaline
      pD2 (-log EC50) values were decreased 3.7 log units as a result of increasing
      cholinergic tone from 22 to 106%, and 2.4 log units by increasing histamine tone
      over a similar range. Furthermore, maximal relaxability of cholinergic tone
      decreased gradually from 100% at low to only 1.3% at supramaximal contraction
      levels, whereas with histamine almost complete relaxation was maintained at all
      concentrations applied. As a result, isoprenaline relaxation was clearly hampered
      with methacholine compared to histamine at equal levels of contractile tone.4. In
      the presence of gallamine, isoprenaline relaxation was facilitated for most
      concentrations of methacholine, and for all concentrations of histamine. These
      changes could be explained by the decreased contraction levels for both
      contractile agonists in the presence of gallamine.5. Isoprenaline-induced
      relaxation of cholinergic contraction was also facilitated by AF-DX 116 as well
      as by pirenzepine and hexahydrosiladiphenidol, and these (small) changes were
      again related to the(small) decreases in cholinergic contraction levels that were
      present in these experiments despite the additional administration of the agonist
      to readjust contractile tone. Similarly, changes in isoprenaline relaxation of
      histamine-induced tone could be explained by different contraction levels.6.
      These results can be explained by the sole involvement of muscarinic M3
      receptors, and provide no evidence for a role of muscarinic M2 receptors in
      functional antagonism in bovine trachea. Furthermore,they stress the importance
      of taking into account non-cholinergic controls as well as contraction levels in
      these experiments.

PMID- 7582490
TI  - 5-Hydroxytryptamine receptors that facilitate excitatory neuromuscular
      transmission in the guinea-pig isolated detrusor muscle.
AB  - 1. In isolated detrusor strips from the guinea-pig urinary bladder, contractile
      responses to electrical field stimulation were mostly mediated by neurally
      released acetylcholine (ACh) and adenosine 5'-triphosphate (ATP). 2. 5
      Hydroxytryptamine (5-HT) produced a concentration-dependent increase in the
      amplitude of stimulated detrusor strip contractions. The 5-HT concentration
      response curve showed a biphasic profile: the high potency phase was obtained at
      sub-micromolar concentrations (10-300 nM), while the low potency phase in the
      range 1-30 microM. The maximum response of the first phase was 30% of the total 5
      HT response. 3. Like 5-HT, the 5-HT3 receptor agonist, 2-methyl-5
      hydroxytryptamine (2-methyl-5-HT: 0.3-100 microM), the 5-HT2 receptor agonist,
      (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 30 nM-3 microM) and the
      5-HT4 receptor agonist, 5-methoxytryptamine (5-MeOT: 0.1-30 microM) potentiated,
      though with lower potency, detrusor contractions. The resulting concentration
      response curves were monophasic in nature. 2-Methyl-5-HT had a maximum effect
      comparable to that of 5-HT. By contrast, the maximal effects of DOI and 5-MeOT
      were only 20% and 30% of that elicited by 30 microM 5-HT, respectively. 4. The 5
      HT3 receptor antagonist, granisetron (0.3 microM) had no effect on the high
      potency phase, but caused a rightward parallel shift of the low potency phase of
      the 5-HT curve (pKB = 7.3). Granisetron(0.3 microM) antagonized with comparable
      affinity (pKB = 7.1) 5-HT-induced responses after pharmacological isolation of 5
      HT3 receptors with the 5-HT1/5-HT2 receptor antagonist, methiothepin (0.3 microM)
      and the 5-HT4 receptor antagonist, GR 125487 (30 nM). Granisetron (0.1, 0.3 and 1
      microM) competitively antagonized the potentiating effect of 2-methyl-5-HT with
      an estimated pA2 of 7.3.5. Methiothepin (0.3 microM) and the 5-HT2A receptor
      antagonist, ketanserin (0.3 microM) produced a slight inhibition of the first
      phase of the 5-HT curve. In the presence of ketanserin, an equimolar
      concentration of methiothepin was ineffective in further reducing the effect of 5
      HT. Similarly, the 5-HT4 receptor antagonist, GR 125487 (30 nM) slightly
      inhibited the first phase of the 5-HT curve. Conversely, this phase was
      suppressed when detrusor strips were coincubated with ketanserin (or
      methiothepin) and GR125487.6. In a separate set of experiments, the interactions
      of 5-HT with either the purinergic or cholinergic components of excitatory
      neuromuscular transmission were investigated. In the presence of hyoscine(1
      microM), 5-HT was mostly effective at sub-micromolar concentrations, while in the
      presence of the P2-purinoceptor antagonist, suramin (300 microM), 5-HT-induced
      potentiation was mainly obtained with micromolar concentrations.7. Thus, in
      electrically stimulated detrusor strips from guinea-pig, 5-HT potentiated
      excitatory neuromuscular transmission by activating at least three separate
      neural 5-HT receptors. These include the 5-HT2A and 5-HT4 receptors, which
      mediate the 5-HT high potency phase mainly by activation of purinergic
      transmission. On the other hand, the potentiating effect caused by micromolar
      concentrations of 5-HT mostly involves cholinergic transmission and is mediated
      by the 5-HT3 receptors.

PMID- 7582486
TI  - Actions of endothelins and sarafotoxin 6c in the rat isolated perfused lung.
AB  - 1. Endothelin (ET) receptors within the vasculature and airways were studied in a
      rat perfused lung model in which pulmonary perfusion pressure (PPP), pulmonary
      inflation pressure (PIP) and lung weight were continuously monitored. 2. The
      vascular potencies of ETs (ET-1 > ET-2 > ET-3) suggest an action via ETA
      receptors. This was confirmed by use of the antagonist, BQ123 (2 microM). The
      vasoconstrictor effects of sarafotoxin 6c (SX6C) also indicated the presence of
      ETB receptors. 3. Lung weight increases induced by ETs appeared to be a
      consequence of their vasoconstrictor potencies. The mixed ET receptor antagonist,
      bosentan (5 microM), markedly attenuated the responses of ET-1 and SX6C on PPP
      and lung weight, further implicating activation of both ETA and ETB receptors in
      these responses. 4. Endothelin-1 (ET-1) induced an accumulation of albumin-bound
      Evans blue dye in orthogradely perfused lungs. Retrograde perfusion attenuated
      the extravasation and increase in lung weight due to ET-1 but significantly
      augmented those induced by SX6C. 5. The bronchoconstrictor actions of ETs (ET-1 =
      ET-2 = ET-3) and SX6C suggest this is an ETB-mediated response. However SX6C was
      more potent than ETs and the dose-response curve was significantly steeper and
      achieved a higher maximum. 6. Indomethacin did not affect the vascular or
      bronchial responses to ET-1 or SX6C. 7. These findings indicate that rat
      pulmonary vasculature contains both ETA and ETB receptors. Retrograde perfusion
      suggests that ETB receptors are located arterially whereas ETA receptors are
      predominantly venous in distribution. Differences in the bronchoconstrictor
      potency of SX6C (compared to ETs) and the antagonism by bosentan may indicate ETB
      receptor heterogeneity in the airways.

PMID- 7582491
TI  - Cytokine-mediated inflammatory hyperalgesia limited by interleukin-10.
AB  - 1. The effect of interleukin-10 (IL-10) upon the hyperalgesic activities in rats
      of bradykinin, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1
      beta), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin E2 (PGE2) and
      carrageenin were investigated in a model of mechanical hyperalgesia. 2.
      Hyperalgesic responses to bradykinin (1 micrograms) were inhibited in a dose
      dependent manner by prior treatment with IL-10 (1-100 ng). 3. Hyperalgesic
      responses to TNF alpha (2.5 pg), IL-1 beta (0.5 pg) and IL-6 (1.0 ng) but not to
      IL-8 (0.1 ng) and PGE2 (50 ng and 100 ng) were inhibited by prior treatment with
      IL-10 (10 ng). 4. Hyperalgesic responses to carrageenin (100 micrograms) were
      inhibited by IL-10 (10 ng) when this cytokine was injected before but not after
      the carrageenin. 5. A monoclonal antibody to mouse IL-10 potentiated the
      hyperalgesic responses to carrageenin (10 micrograms) and TNF alpha (0.025 pg)
      but not that to IL-8 (0.01 ng). 6. In in vitro experiments in human peripheral
      blood mononuclear cells (MNCs), IL-10 (0.25-4.0 ng ml-1) inhibited in a dose
      dependent manner PGE2 production by MNCs stimulated with IL-1 beta (1-64 ng ml-1)
      or endotoxin (lipopolysaccharide, LPS, 1 iu = 143 pg ml-1) but evoked only small
      increases in IL-1ra production. 7. These data suggest that IL-10 limits the
      inflammatory hyperalgesia evoked by carrageenin and bradykinin by two mechanisms:
      inhibition of cytokine production and inhibition of IL-1 beta evoked PGE2
      production. Our data suggest that the latter effect is not mediated via IL-10
      induced IL-Ira and may result from suppression by IL-10 of prostaglandin H
      synthase-2 (COX-2).

PMID- 7582492
TI  - Comparison of the interaction of agmatine and crude methanolic extracts of bovine
      lung and brain with alpha 2-adrenoceptor binding sites.
AB  - 1. In the present study we have evaluated whether alpha 2-adrenoceptor binding
      sites on bovine cerebral cortex membranes labelled by [3H]-clonidine, [3H]
      idazoxan and [3H]-RX-821002 can distinguish between known agonists and
      antagonists. This model has then been used to compare the binding profiles of the
      putative non-catecholamine, clonidine-displacing substance (CDS), agmatine and
      crude methanolic extracts of bovine lung and brain. 2. Saturation studies carried
      out in the presence and absence of noradrenaline, 10 mumol 1(-1), revealed that
      the maximum number of binding sites on bovine cerebral cortex membranes for [3H]
      idazoxan and [3H]-RX-821002 were approximately 60-80% greater than those for [3H]
      clonidine (62.6 fmol mg-1 protein). Rauwolscine, the selective alpha 2
      adrenoceptor antagonist, was approximately 100 fold more potent against each of
      the ligands than the selective alpha 1-adrenoceptor diastereoisomer,
      corynanthine. Also, the pKi value for the selective alpha 1-adrenoceptor prazosin
      against each ligand was less than 6. 3. Adrenaline, UK-14034, rauwolscine,
      corynanthine, RX-811059 and prazosin produced concentration-dependent inhibition
      of binding of all three 3H-ligands. The agonists, adrenaline and UK-14304, were
      approximately 5 and 10 fold less potent against [3H]-idazoxan and [3H]-RX-821002,
      respectively, than against [3H]-clonidine. In marked contrast, the antagonists,
      rauwolscine, corynanthine, RX-811059 and prazosin exhibited a different profile,
      being approximately 2-3 fold more potent against sites labelled by [3H]-RX-821002
      and [3H]-idazoxan compared to sites labelled by [3H]-clonidine. 4. Agmatine and
      histamine produced a concentration-dependent displacement of [3H]-clonidine, [3H]
      idazoxan and [3H]-RX-821002 binding to bovine cerebral cortex membranes. The pKi
      values for agmatine and histamine were independent of the 3H-ligand employed,
      approximately 4.8 and 4.5,respectively.5. Crude methanolic extracts of bovine
      brain and lung produced a concentration-dependent inhibition of [3H]-clonidine
      binding to bovine cerebral cortex membranes (>90%). Based on the volume of the
      extract that caused 50% inhibition of [3H]-clonidine binding, bovine lung
      contains 3 fold more CDS than bovine brain. Both extracts were at least 5 fold
      more potent against a2-adrenoceptor sites labelled by[3H]-clonidine than those
      labelled by [3H]-idazoxan and [3H]-RX-821002.6. All three 3H-ligands label the
      same population of alpha2-adrenoceptor binding sites on bovine cerebral cortex
      membranes, but [3H]-clonidine appears to label selectively the 'agonist' state of
      the sites: for which known agonists, adrenaline and UK-14304, exhibit a higher
      affinity. Our results indicate that neither agmatine nor histamine can account
      for the CDS activity present in crude extracts of bovine brain and lung.
      Moreover, these extracts appear to possess a binding profile similar to that of
      adrenaline and UK-14304, suggesting that they may possess agonist activity.

PMID- 7582493
TI  - Effects of mastoparan 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 the effects of mastoparan upon the late stages of
      the adrenocorticotrophin (ACTH) secretory pathway. 2. Mastoparan (10(-8)-10(-5)
      M), an activator of heterotrimeric guanosine 5'-triphosphate binding proteins (G
      proteins), stimulated ACTH secretion from electrically-permeabilized AtT-20 cells
      in a concentration-dependent manner in the effective absence of calcium ions with
      a threshold of 10(-6) M. Guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) (10(
      8)-10(-4) M) also stimulated ACTH secretion from electrically-permeabilized AtT
      20 cells in a concentration-dependent manner in the effective absence of calcium
      ions with a threshold of 10(-6) M. This GTP-gamma-S-evoked secretion is
      consistent with previous studies which demonstrated that a G-protein, termed GE,
      mediates calcium evoked ACTH secretion from AtT-20 cells. GTP-gamma-S-evoked
      secretion however was not as great as that obtained in response to mastoparan. 3.
      Both mastoparan (10(-5) M) and GTP-gamma-S (10(-4) M) stimulated ACTH secretion
      from electrically-permeabilized AtT20 cells in a time-dependent manner. A time of
      30 min was adopted as the standard incubation period for the study of both
      mastoparan and GTP-gamma-S-stimulated ACTH secretion from permeabilized AtT-20
      cells. 4. Mastoparan (10(-8)-10(-5) M) stimulated ACTH secretion from
      permeabilized AtT-20 cells to the same extent in the presence and absence of the
      protein kinase C (PKC) inhibitor, chelerythrine chloride (10(-5) M). 5.
      Mastoparan (10-8 10-5 M)-stimulated ACTH secretion from permeabilized AtT-20
      cells was significantly reduced in the presence of guanosine 5'-O-(2
      thiodiphosphate) (GDP-beta-S, 10-4 M).6. The mastoparan analogue, Mas-7 (10-8-10
      5 M) stimulated ACTH secretion from permeabilized AtT-20 cells to a greater
      extent than mastoparan (10-8 10-5 M) however, the mastoparan analogue Mas-17 (10
      8- 10-5 M) had no effect upon ACTH secretion from permeabilized AtT-20 cells.7.
      Mastoparan (10-8-10-5 M) stimulated ACTH secretion from permeabilized AtT-20
      cells in the presence and absence of ATP, normally present in the standard
      permeabilization medium at a concentration of 5 mM. Mastoparan (10-8- 10-5 M)
      stimulated ACTH secretion as well as control secretion was reduced when ATP was
      omitted.8. The results of the present study demonstrate that mastoparan
      stimulated ACTH secretion from permeabilized AtT-20 cells and displayed
      characteristics consistent with calcium ion- and GTP-y-gamma-S-stimulated ACTH
      secretion from permeabilized AtT-20 cells. This suggests that in permeabilized
      AtT-20 cells, mastoparan directly activates GE and that this G-protein may be a
      heterotrimeric G-protein. This study also suggests mastoparan may be a useful
      alternative to GTP-gamma-S as a means of directly activating GE.

PMID- 7582495
TI  - Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased
      content of L-arginine in regenerated endothelial cells.
AB  - 1. We examined regeneration of endothelial cells (ECs), neointima formation,
      decreased endothelium-dependent relaxation (EDR) and changes in the contents of L
      arginine, NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG-dimethylarginine
      (ADMA) and symmetrical NG,NG-dimethylarginine (SDMA) in the regenerated ECs, 6
      weeks after balloon denudation of the rabbit carotid artery. 2. Regeneration of
      ECs was completed in 6 weeks and a significant neointima formation accompanied by
      the decreased EDR was observed. 3. L-NMMA and ADMA contents in the regenerated
      ECs (23.5 +/- 4.3 and 21.2 +/- 2.0 pmol mg-1 DNA, respectively) were
      significantly (P < 0.05 and P < 0.01) higher than those in the control ECs (8.8
      +/- 3.0 and 7.4 +/- 1.9 pmol mg-1 DNA, respectively), whereas L-arginine was
      significantly (P < 0.005) decreased in the regenerated ECs (31,470 +/- 1,050 pmol
      mg-1 DNA) as compared to that in the control ECs (47,870 +/- 1,890 pmol mg-1
      DNA). SDMA content was below the assay limits. 4. L-NMMA and ADMA, but not SDMA,
      inhibited the EDR induced by acetylcholine in a concentration-dependent manner.
      The inhibition with L-NMMA and ADMA was prevented by an addition of L-arginine,
      but not by D-arginine. 5. These results suggest that the accumulation of
      endogenous inhibitors for nitric oxide synthesis and decreased L-arginine content
      are associated with decreased NO production/release from regenerated ECs and
      neointima formation.

PMID- 7582494
TI  - Increase of noradrenaline release in the hypothalamus of freely moving rat by
      postsynaptic 5-hydroxytryptamine1A receptor activation.
AB  - 1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic
      neurones in the brain, but the precise mechanism of regulation of noradrenaline
      (NA) release by 5-HT1A receptors has not been defined. The present study
      describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5
      (3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC
      242), on NA release in the hypothalamus using microdialysis in the freely moving
      rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular
      levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the
      hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n
      propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1)
      mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4.
      The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by
      pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5.
      Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT
      reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into
      the hypothalamus, had no effect on NA release. 6. Intracerebroventricular
      injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT
      content, but the treatment affected neither basal NA levels nor the MKC-242
      induced increase in NA release. 7. The effect of MKC-242 in increasing NA release
      was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day
      for 2 weeks). 8. The present results suggest that activation of postsynaptic 5
      HT1A receptors increases NA release in the hypothalamus.

PMID- 7582497
TI  - Endogenous modulation of excitatory amino acid responsiveness by tachykinin NK1
      and NK2 receptors in the rat spinal cord.
AB  - 1. The effects of selective tachykinin (neurokinin, NK) NK1 and NK2 receptor
      antagonists have been examined on spinal neurones in alpha-chloralose
      anaesthetized, spinalized rats. They were tested for effects on responses both to
      excitatory amino acids (EAA) and to noxious heat stimuli. They were also tested
      for their ability to reverse the actions of selective NK agonists. 2. The NK1
      selective antagonists GR82334 (peptide) and CP-99,994 (non-peptide), when applied
      by microiontophoresis, both reduced responses to kainate > AMPA > NMDA.
      Intravenous CP-99,994 (3 mg kg-1) also reduced responses to kainate but had
      inconsistent effects on nociceptive responses. 3. GR82334, applied
      microiontophoretically, reduced the enhancement by the selective NK1 agonist,
      GR73632 of both responses to EAAs and background activity. Systemic CP-99,994 (<
      or = 10 mg kg-1) failed to reverse the effects of GR73632. 4. The selective
      peptide NK2 antagonist, GR103537, had no consistent effects on responses to EAAs
      when applied by iontophoresis. In contrast, the non-peptide NK2 antagonist,
      GR159897, administered systemically (0.5-2 mg kg-1, i.v.) enhanced responses to
      kainate (but not NMDA); responses to noxious heat were enhanced only weakly. 5.
      Iontophoretically-administered GR103537 attenuated the effects of the NK2 agonist
      GR64349, which selectively reduced responses to kainate compared to those to
      NMDA. Systemically administered GR159897 (< or = 2 mg kg-1, i.v.) caused little
      antagonism of the effects of GR64349. 6. The data indicate that under these
      conditions the non-peptide antagonists are not reliable at reversing the actions
      of selective NK agonists. 7. These results suggest that there is a tonic release
      of endogenous tachykinins that can modulate glutamatergic neurotransmission in
      the spinal cord. They provide further support for the hypothesis that release of
      endogenous NKs acting on NK1 and NK2 receptors can promote NMDA receptor mediated
      glutamatergic transmission.

PMID- 7582496
TI  - Modulation of excitatory amino acid responses by tachykinins and selective
      tachykinin receptor agonists in the rat spinal cord.
AB  - 1. The effects of tachykinins and agonists selective for the three subtypes of
      neurokinin (NK) receptor have been tested on spinal neuronal responses both to
      the excitatory amino acids (EAAs) NMDA, AMPA and kainate, and to noxious heat
      stimuli. The agonists were applied by microiontophoresis in in vivo experiments
      in alpha-chloralose-anaesthetized, spinalized rats. 2. The NK1-selective agonist,
      GR 73632, enhanced responses to all three EAAs similarly, whilst the NK2
      selective agonist, GR64349, reduced responses to AMPA and kainate without
      affecting those to NMDA, and the NK3 selective agonist, senktide, enhanced
      responses to AMPA and kainate. 3. The endogenous ligands substance P (SP) and
      neurokinin A (NKA) both enhanced responses to NMDA with little effect on
      responses to kainate, whereas neurokinin B (NKB) selectively enhanced responses
      to kainate without affecting those to NMDA. 4. The effects of GR73632 on EAA
      responses showed some differences between the dorsal and ventral horn, with more
      selectivity towards enhancement of NMDA responses in the ventral horn, but a
      smaller maximum effect. 5. Background activity was significantly enhanced by
      GR73632, GR64349, SP and NKA but not by senktide or NKB. GR73632 had the greatest
      effect on background firing, but this action was variable between cells and was
      related both to the location within the spinal cord and to the degree of
      spontaneous activity prior to GR73632 administration. 6. Responses to noxious
      heat were enhanced consistently only by NKA. 7. These data show that selective
      agonists for the tachykinin receptors are capable of modulating EAA responses
      differentially. SP, NKA and NKB appear to act via more than one receptor type
      when modulating EAA responses in vivo. This indicates that NK-EAA interactions
      can be more specific than suggested hitherto, with the combined actions at NKI
      and NK2 receptors biasing EAA responsiveness towards NMDA receptor mediated
      functions, whereas NK3 receptor activation would have the opposite effect. The
      physiological role of such interactions is likely to be complex.

PMID- 7582498
TI  - NANC neurotransmission in lamina propria of the rabbit urethra: regulation by
      different subsets of calcium channels.
AB  - 1. Electrical field stimulation (EFS) of the rabbit urethral lamina propria
      elicited a frequency-dependent non-adrenergic, non-cholinergic (NANC) relaxation,
      which was abolished by N omega-nitro-L-arginine (L-NOARG). 2. omega-Conotoxin
      GVIA, a selective blocker of N-type voltage-operated calcium channels (VOCCs),
      and omega-conotoxin MVIIC (blocker of N- and Q-type VOCCs) inhibited the NANC
      relaxation, and the inhibition was inversely related to the frequency of
      stimulation. Combined, the two toxins were more effective than omega-contoxin
      GVIA alone. 3. The relaxation induced by the nitric oxide (NO) donor, 3
      morpholino-sydnonimine (SIN-1) was not affected by omega-conotoxin MVIIC. 4.
      omega-Agatoxin IVA (blocker of P-type VOCCs) did not attenuate the NANC
      relaxation. 5. Reduction of the calcium concentration from 1.5 to 0.5 mM reduced
      the NANC relaxation at low but not at high frequencies of stimulation; the
      relaxation induced by SIN-1 was not affected. 6. EFS (20 Hz, 30 s) increased the
      cyclic GMP level 3 fold in normal Krebs solutions, but was unable to enhance
      significantly the cyclic GMP level after calcium omission. L-NOARG reduced the
      cyclic GMP content in 'calcium-free' medium, indicating an ongoing NO synthesis
      that was independent of extracellular calcium. 7. Caffeine, ryanodine and
      thapsigargin (inhibitors of sarcoplasmic calcium release), and CGP 37157
      (inhibitor of mitochondrial sodium/calcium exchange) had no effect on the NANC
      relaxation. 8. It is suggested that nitrergic nerve activation in the rabbit
      urethral lamina propria is mediated in partby N-type (omega-conotoxin GVIA
      sensitive) and in part by Q-type (omega-conotoxin MVIIC-sensitive) VOCCs.With
      high frequences of stimulation, another mechanism, possibly calcium-independent,
      appears to become operational.

PMID- 7582499
TI  - Effects of BRL55834 in rat portal vein and bovine trachea: evidence for the
      induction of a glibenclamide-resistant, ATP-sensitive potassium current.
AB  - 1. The effects of the benzopyran K-channel opener, BRL55834, on mechanical
      activity in bovine trachealis and rat portal vein were studied together with
      membrane currents in freshly-isolated single cells derived from these tissues. 2.
      BRL55834 (3 nM-1 microM) produced a concentration-dependent relaxation of bovine
      trachealis precontracted with 100 microM histamine and reduced the spontaneous
      mechanical activity of rat portal veins, effects which were antagonized by
      glibenclamide (1-10 microM) but were not reversible on washing. In contrast,
      charybdotoxin (250 nM) did not modify the spasmolytic effect of BRL55834 in
      bovine trachealis. 3. BRL55834 (10 nM-10 microM) did not relax segments of bovine
      trachealis precontracted with 80 mM KCl. 4. In some freshly-isolated single cells
      from bovine trachealis held at -10 mV, BRL55834 (3 microM) induced a time
      independent outward K-current which was partially resistant to inhibition by
      glibenclamide (10 microM). In other cells, a very noisy, outwardly-rectifying and
      charybdotoxin-sensitive current developed in the presence of BRL55834 (3 microM)
      and in time-matched control cells. 5. In freshly-isolated single cells from rat
      portal vein held at -10 mV, BRL55834 (3 microM) induced a time- and calcium
      independent outward K-current which was partially resistant (approximately 25%
      inhibition at +40 mV) to subsequent inhibition by glibenclamide (10 microM). In
      contrast, levcromakalim induced a time-independent outward K-current which was
      completely inhibited by glibenclamide 10 microM. 6. With the non-hydrolysable ATP
      analogue, AMP-PCP (5 mM), in the pipette, the ability of BRL55834 to induce a
      time-independent K-current in portal vein cells was markedly reduced
      (approximately 80% inhibition at +40 mV) whereas the effects of 10 microM
      levcromakalim were totally inhibited. 7. The glibenclamide-resistant current
      component induced by BRL55834 was totally inhibited by phentolamine (100 microM),
      a concentration that had no effect on the peak current (IBK(Ca)) induced by
      NS1619 (33 microM). 8. Stationary fluctuation analysis of the noise associated
      with the glibenclamide-insensitive K-current induced by BRL55834 in rat portal
      vein cells indicated that the unitary current flowing through the underlying
      channels was 0.26 pA at -10 mV, a value inconsistent with the involvement of
      BKCa. 9. It is concluded that the relaxations of both bovine trachea and rat
      portal vein produced by BRL55834 are associated with the opening of K-channels.
      These are probably identical to the ATP-sensitive K-channel opened by
      levcromakalim, although the involvement of an additional K-channel cannot be
      excluded. The reduced sensitivity of the BRL55834-induced changes to
      glibenclamide and toAMP-PCP may result from avid binding of BRL55834 to its site
      of action.

PMID- 7582501
TI  - Glucocorticoid-induced annexin 1 secretion by monocytes and peritoneal
      leukocytes.
AB  - 1. We have studied the ability of the glucocorticoid, dexamethasone, to induce
      annexin 1 secretion by either human blood monocytes or rat peritoneal leukocytes.
      2. The in vivo treatment of rats with dexamethasone (1.25 mg kg-1) selectively
      induced secretion of annexin 1 by peritoneal leukocytes, as assessed by
      incubating these cells in culture medium. Annexin 1 secretion was also induced in
      human cultured monocytes, in vitro, by 10(-6) M dexamethasone. 3. Annexin 1
      secretion was inhibited in the presence of 20 mM NH4Cl or by conducting the
      experiments at 18 degrees C. In contrast, it was not inhibited by monensin,
      nocodazole or brefeldin A. 4. The time necessary for annexin 1 synthesis and
      secretion was less than 15 min. 5. These data indicate that glucocorticoids
      induce annexin 1 secretion by monocytes or peritoneal leukocytes. Because it is
      not inhibited by monensin, nocodazole or brefeldin A and it is rapid, annexin 1
      secretion seems to occur by the secretory pathway similar to that used by several
      cytosolic proteins such as interleukin-1 beta.

PMID- 7582503
TI  - Phosphorus-containing peptides as mixed inhibitors of endopeptidase 3.4.24.15 and
      3.4.24.16: effect on neurotensin degradation in vitro and in vivo.
AB  - 1. We have examined several phosphorus-containing peptides as potential mixed
      inhibitors of two neurotensin-degrading zinc metallopeptidases, endopeptidase
      3.4.24.15 and endopeptidase 3.4.24.16. 2. Among a series of 13 phosphonamide
      peptides, N-(2-(2-naphtyl)ethylphosphonyl-glycyl-prolyl-norleucine
      (phosphodiepryl 08) was found to inhibit potently the hydrolysis of neurotensin
      by purified endopeptidase 3.4.24.15 and 3.4.24.16 with an identical Ki value of
      0.4 nM. 3. Phosphodiepryl 08 displayed a strong selectivity towards the two
      peptidases since it failed to inhibit several other zinc-containing peptidases
      such as endopeptidase 3.4.24.11, angiotensin-converting enzyme, aminopeptidase M,
      leucine aminopeptidase and carboxypeptidases A and B. 4. The protective effect of
      phosphodiepryl 08 on neurotensin degradation was examined in vitro and in vivo in
      central and peripheral bioassays. 5. Phosphodiepryl 08 virtually abolished
      neurotensin degradation by 4-day-old plated pure cultured neurones from mouse
      embryos and greatly potentiated neurotensin-induced antinociception in the mouse
      hot plate test. 6. In the periphery, phosphodiepryl 08 inhibited neurotensin
      degradation by membranes prepared from isolated longitudinal smooth muscle of
      guinea-pig ileum and greatly potentiated the neurotensin-induced contraction of
      the same longitudinal smooth muscle preparation. 7. Our study indicates that
      phosphodiepryl 08 behaves as a potent and selective mixed inhibitor of
      endopeptidase 3.4.24.15 and 3.4.24.16 and can be used as a powerful agent to
      prevent neurotensin degradation, in vitro and in vivo, in central and peripheral
      assays.

PMID- 7582500
TI  - Endothelial modulation of vasoconstrictor responses to endothelin-1 in human
      placental stem villi small arteries.
AB  - 1. The aim of this study was to assess the role of endothelial cells in the
      modulation of vasocontractile responses to endothelin-1 (ET-1) of human placental
      vasculature. 2. Isolated stem villi small arteries (diameter = 170-250 microns)
      were obtained from healthy parturients who underwent caesarean surgery during the
      39th week of pregnancy for cephalo-pelvic disproportion. Isometric tension was
      measured in vascular rings mounted in a myograph system and challenged with ET-1
      (10(-12) to 10(-6) M). 3. The vasocontractile response to ET-1 was significantly
      (P < 0.001) increased in endothelial-denuded (active tension = 1156 +/- 214 mN mm
      1) as compared with endothelial-preserved vascular rings (active tension = 458 +/
      48 mN mm-1). This difference was significantly (P < 0.05) but only partly
      abolished by the NO synthase inhibitor N omega-nitro-L-arginine (L-NOARG, 10(-4)
      M). 4. In endothelial-preserved rings submaximally precontracted with 5
      hydroxytryptamine (10(-6) M), ET-1 (10(-12) to 10(-9) M) induced dose-dependent
      relaxation (maximum relaxation = 70 +/- 7%) at 10(-9) M, which was followed, at
      higher doses (10(-8) to 10(-6) M), by a contraction. In contrast, no relaxation
      was seen in endothelial-denuded rings. The relaxation in rings with endothelium
      was significantly (P < 0.001) reduced by L-NOARG (10(-4) M. Moreover, it was
      totally abolished by combined pretreatment with L-NOARG (10(-4) M) and the
      sulphonylurea glibenclamide (10(-5) M). 5. In conclusion, endothelial cells
      modulate the vascular responses to ET-1 through the release of NO and a substance
      acting on the ATP-sensitive K+ channel of smooth muscle of stem villi small
      arteries from healthy parturients.

PMID- 7582502
TI  - Potentiation by viral respiratory infection of ovalbumin-induced guinea-pig
      tracheal hyperresponsiveness: role for tachykinins.
AB  - 1. We investigated whether virus-induced airway hyperresponsiveness in guinea
      pigs could be modulated by pretreatment with capsaicin and whether viral
      respiratory infections could potentiate ovalbumin-aerosol-induced tracheal
      hyperresponsiveness. 2. Animals were inoculated intratracheally with bovine
      parainfluenza-3 virus or control medium 7 days after treatment with capsaicin (50
      mg kg-1, s.c.). Four days after inoculation, tracheal contractions were measured
      to increasing concentrations of substance P, histamine and the cholinoceptor
      agonist, arecoline. 3. In tracheae from virus-infected guinea-pigs, contractions
      in response to substance P, histamine and arecoline were significantly enhanced
      (P < 0.01) by 144%, 46% and 77%, respectively. Capsaicin pretreatment inhibited
      the hyperresponsiveness to substance P partly (62%) and to histamine and
      arecoline completely. 4. In another series of experiments animals were first
      sensitized with ovalbumin (20 mg kg-1, i.p.). After 14 days animals were exposed
      to either saline or ovalbumin aerosols for 8 days. After 4 aerosol exposures (4
      days) animals were inoculated with either parainfluenza-3 virus or control
      medium. One day after the last ovalbumin aerosol, tracheal contraction in
      response to increasing concentrations of substance P, histamine and arecoline was
      measured. 5. Tracheae from ovalbumin-aerosol-exposed control inoculated animals
      showed a similar degree of airway hyperresponsiveness to saline-aerosol-exposed
      virus-treated guinea-pigs. Virus inoculation of ovalbumin-treated animals
      significantly potentiated the tracheal contractions to substance P compared to
      either of the treatments alone. The contractions in response to histamine and
      arecoline were only slightly enhanced. 6. In conclusion, sensory nerves and/or
      tachykinins are involved in virus-induced airway hyperresponsivenessin guinea
      pigs and viral respiratory infections can potentiate the increase in tracheal
      responsiveness to bronchoconstrictor agonists after ovalbumin exposure.

PMID- 7582504
TI  - Interaction between a selective 5-HT1A receptor antagonist and an SSRI in vivo:
      effects on 5-HT cell firing and extracellular 5-HT.
AB  - 1. The acute inhibitory effect of selective 5-hydroxytryptamine (serotonin)
      reuptake inhibitors (SSRIs) on 5-HT neuronal activity may offset their ability to
      increase synaptic 5-HT in the forebrain. 2. Here, we determined the effects of
      the SSRI, paroxetine, and a novel selective 5-HT1A receptor antagonist, WAY
      100635, on 5-HT cell firing in the dorsal raphe nucleus (DRN), and on
      extracellular 5-HT in both the DRN and the frontal cortex (FCx). Extracellular
      electrophysiological recording and brain microdialysis were used in parallel
      experiments, in anaesthetized rats. 3. Paroxetine dose-dependently inhibited the
      firing of 5-HT neurones in the DRN, with a maximally effective dose of
      approximately 0.8 mg kg-1, i.v. WAY 100635 (0.1 mg kg-1, i.v.) both reversed the
      inhibitory effect of paroxetine and, when used as a pretreatment, caused a
      pronounced shift to the right of the paroxetine dose-response curve. 4.
      Paroxetine (0.8 mg kg-1, i.v.), doubled extracellular 5-HT in the DRN, but did
      not alter extracellular 5-HT in the FCx. A higher dose of paroxetine (2.4 mg kg
      1, i.v.) did increase extracellular 5-HT in the FCx, but to a lesser extent than
      in the DRN. Whereas 0.8 mg kg-1, i.v. paroxetine alone had no effect on
      extracellular 5-HT in the FCx, in rats pretreated with WAY 100635 (0.1 mg kg-1),
      paroxetine (0.8 mg kg-1, i.v.) markedly increased extracellular 5-HT in the FCx.
      5. In conclusion, pretreatment with the selective 5-HT1A receptor antagonist, WAY
      100635, blocked the inhibitory effect of paroxetine on 5-HT neuronal activity in
      the DRN and, at the same time, markedly enhanced the effect of paroxetine on
      extracellular 5-HT in the FCx. These results may be relevant to recent clinical
      observations that 5-HT1A receptor antagonists in combination with SSRIs have a
      rapid onset of antidepressant effect.

PMID- 7582506
TI  - Inhibition by cromoglycate and some flavonoids of nucleoside diphosphate kinase
      and of exocytosis from permeabilized mast cells.
AB  - 1. The anti-allergic compound, cromoglycate, is reported to possess affinity for,
      and to suppress the autophosphorylation of a 72kDa protein having the sequence of
      nucleoside diphosphate kinase (NDPK). 2. We have tested the ability of
      cromoglycate, and a panel of ten structurally related flavonoids of plant origin,
      to inhibit the NDPK reaction and the exocytotic process of permeabilized mast
      cells. The conditions of permeabilization (use of an isotonic medium based on
      sodium glutamate) were selected to ensure that NDPK activity would be an
      essential component in the induction of Ca(2+)-induced exocytosis in which ATP is
      required for generation of GTP. For comparison, we also measured the inhibition
      of exocytosis induced by GTP-gamma-S; this proceeds in the absence of ATP and
      bypasses the need for NDPK activity. 3. We found that cromoglycate does not
      discriminate between Ca2+ and GTP-gamma-S-induced exocytosis and is a poor
      inhibitor of NDPK activity. Concentrations in the millimolar range are required
      for inhibition of all these functions. By comparison, many of the flavonoids are
      effective at concentrations in the micromolar range. 4. While we were unable to
      discern any systematic relationships between their ability to inhibit the three
      functions, two compounds, quercetin and genistein, inhibit Ca(2+)-induced, but
      not GTP-gamma-S-induced exocytosis. Inhibition of the late stages of the stimulus
      response pathway in mast cells by these compounds is therefore likely to be due
      to inhibition of NDPK and the consequent failure to generate GTP.

PMID- 7582505
TI  - The effect of neuropeptide Y on sodium, chloride and potassium transport across
      the rat distal colon.
AB  - 1. Neuropeptide Y (NPY; 10(-10)-10(-7) mol l-1) reduced basal short-circuit
      current (Isc) in a concentration-dependent manner in the rat distal colon but was
      ineffective in the proximal colon. 2. The action of NPY was dependent upon the
      presence of Cl- and HCO3- anions and was blocked by prior treatment of the tissue
      with a Cl- channel blocker. The decrease in Isc was associated with an increase
      in mucosa-to-serosa fluxes of Na+, Rb+ (K+) and Cl-, whereas the serosa-to-mucosa
      flux of Cl- was decreased. 3. The size of the inhibitory NPY effect was linearly
      correlated with the height of the basal Isc, i.e. it inhibited 55% of basal
      secretory Isc. 4. The action of NPY was unaffected by indomethacin and
      tetrodotoxin, when given alone, but was abolished, when the basal Isc was
      decreased to values near zero by a combination of both inhibitors. This
      inhibition could be overcome by restoring basal Isc with prostaglandin E2,
      indicating that the effect of NPY is not mediated by nerves or prostaglandins,
      but that NPY is only effective, when anion secretion is stimulated by the
      spontaneous release of neurotransmitters and prostaglandins. 5. NPY inhibited the
      increase in Isc induced by veratridine and prostaglandin E2, but it had no effect
      on the Isc induced by direct stimulation of the adenylate cyclase with forskolin,
      or on Isc induced by stimulation of the Ca(2+)-pathway with carbachol. Inhibition
      of the response to veratridine or prostaglandin E2 by NPY showed the same
      dependence on the height of the ISC just prior to addition of NPY as seen in
      control conditions, i.e. NPY inhibited 55% of cyclic AMP-mediated secretion.6.
      These results suggest that the effect of NPY is mediated by an inhibition of
      cyclic AMP-stimulated secretion, which is stimulated in the rat distal colon by a
      continuous release of prostaglandins and neurotransmitters.

PMID- 7582507
TI  - RS 39604: a potent, selective and orally active 5-HT4 receptor antagonist.
AB  - 1. Selective antagonism of 5-HT4 receptors may provide therapeutic benefit in
      certain disorders of the myocardium, alimentary and lower urinary tract. We now
      report on RS 39604, a novel and selective 5-HT4 receptor antagonist and compare
      its pharmacological properties with those of SB 204070. 2. In guinea-pig striatal
      membranes, both RS 39604 and SB 204070 inhibited specific binding of [3H]-GR
      113808 in a concentration-dependent manner yielding pKi estimates of 9.1 and
      10.9, respectively. RS 39604 displayed a low affinity (pKi < 6.5) for 5-HT1A, 5
      HT2C, 5-HT3, alpha 1c, D1, D2, M1, M2, AT1, B1 and opioid mu receptors and
      moderate affinity for sigma 1, (pKi = 6.8) and sigma 2 (pKi = 7.8) sites. 3. In
      the rat isolated oesophagus, precontracted with carbachol, RS 39604 (30-300 nM)
      behaved as a competitive antagonist towards 5-HT-induced relaxation (pA2 = 9.3;
      Schild slope = 1.0). We and others have shown previously that SB 204070 behaves
      as an unsurmountable antagonist in this preparation (pA2 approximately 10.5). In
      the guinea-pig isolated ileal mucosa, RS 39604 (30 nM) antagonized 5-MeOT-induced
      increase in short-circuit current (pA2 = 9.1). 4. In anaesthetized vagotomized
      micropigs, RS 39604, administered by the i.v. or intraduodenal (i.duod.) route,
      produced dose-dependent inhibition of 5-HT-induced tachycardia (ID50 = 4.7
      micrograms kg-1, i.v. and 254.5 micrograms kg-1, i.duod). At maximal doses of 30
      micrograms kg-1, i.v. and 6 mg kg-1, i.duod., the inhibitory effects of RS 39604
      lasted for more than 6 h. In this preparation, SB 204070 was as potent as RS
      39604by the i.v. route but was inactive by the intraduodenal route at doses up to
      3 mg kg-1.5. In conscious mice, RS 39604, administered by the i.p. or p.o. route,
      produced dose-depend entinhibition of 5-hydroxytryptophan (5-HTP)-induced
      diarrhoea (ID50= 81.3 microg kg-1, i.p. and 1.1 mg kg-1,p.o.). In this assay, SB
      204070 was inactive by the oral route at doses up to 30 mg kg-1.6. In
      anaesthetized guinea-pigs, RS 39604 antagonized the contractile effect of 5-HT in
      the proximal colon by producing parallel, dextral displacement of the dose
      response curve to 5-HT. The mean dose ratios to 5-HT at 0.1 mg kg-1, i.v., 1 mg
      kg-1, i.v. and 10 mg kg-1, i.duod. were 4.6, 30.7 and 10.8,respectively. SB
      204070 behaved as an unsurmountable antagonist in this assay.7. In a model of
      visceral pain in conscious rats, RS 39604 (0.01-1 mg kg-1, i.v.) did not affect
      colorectal distension-induced increases in arterial pressure whereas morphine (1
      mg kg-1, i.v.) produced significant inhibition of the response, implying that 5
      HT4 receptors are not involved in nociception in this model.8. The data suggest
      that RS 39604 is a high affinity and selective 5-HT4 receptor antagonist that is
      orally active and long-lasting in vivo. It is concluded that RS 39604 may be the
      preferable probe to use for investigating the physiological and
      pathophysiological role of 5-HT4 receptors in vivo.

PMID- 7582509
TI  - [3H]-lifarizine, a high affinity probe for inactivated sodium channels.
AB  - 1. [3H]-lifarizine bound saturably and reversibly to an apparently homogeneous
      class of high affinity sites in rat cerebrocortical membranes (Kd = 10.7 +/- 2.9
      nM; Bmax = 5.10 +/- 1.43 pmol mg-1 protein). 2. The binding of [3H]-lifarizine
      was unaffected by sodium channel toxins binding to site 1 (tetrodotoxin), site 3
      (alpha-scorpion venom) or site 5 (brevetoxin), Furthermore, lifarizine at
      concentrations up to 10 microM had no effect on [3H]-saxitoxin (STX) binding to
      toxin site 1. Lifarizine displaced [3H]-batrachotoxinin-A 20-alpha-benzoate (BTX)
      binding with moderate affinity (pIC50 7.31 +/- 0.24) indicating an interaction
      with toxin site 2. However, lifarizine accelerated the dissociation of [3H]-BTX
      and decreased both the affinity and density of sites labelled by [3H]-BTX,
      suggesting an allosteric interaction with toxin site 2. 3. The binding of [3H]
      lifarizine was voltage-sensitive, binding to membranes with higher affinity than
      to synaptosomes (pIC50 for cold lifarizine = 7.99 +/- 0.09 in membranes and 6.68
      +/- 0.14 in synaptosomes). Depolarization of synaptosomes with 130 mM KCl
      increased the affinity of lifarizine almost 10 fold (pIC50 = 7.86 +/- 0.25). This
      suggests that lifarizine binds selectively to inactivated sodium channels which
      predominate both in the membrane preparation and in the depolarized synaptosomal
      preparation. 4. There was negligible [3H]-lifarizine and [3H]-BTX binding to
      solubilized sodium channels, although [3H]-STX binding was retained under these
      conditions. 5. The potencies of a series of compounds in displacing [3H]
      lifarizine from rat cerebrocortical membranes correlated well with their
      affinities for inactivated sodium channels estimated from whole-cell voltage
      clamp studies in the mouse neuroblastoma cell line, NIE-115 (r=0.96).6. These
      results show that [3H]-lifarizine is a high affinity ligand for neuronal sodium
      channels which potently and selectively labels a site, allosterically linked to
      toxin binding site 2, associated within activated sodium channels.

PMID- 7582510
TI  - Pharmacological profile of the novel P2T-purinoceptor antagonist, FPL 67085 in
      vitro and in the anaesthetized rat in vivo.
AB  - 1. The role of endogenous ADP in platelet aggregation in vivo remains unclear due
      to the lack of suitable P2T-antagonist probes. This paper describes the potency,
      selectivity and specificity of the novel P 2T-purinoceptor antagonist, FPL 67085
      (2-propylthio-D-beta,gamma-dichloromethylene ATP) both in vitro and in the
      anaesthetized rat in vivo. 2. FPL 67085 (3-30 nM) produced concentration
      dependent rightward displacement of the concentration-effect (E/[A]) curve for
      ADP-induced aggregation of human washed platelets with no effect on ADP
      independent aggregation at < or = 10 microM. 3. Logistic fitting of ADP E/[A]
      data indicated that the antagonist effect of FPL 67085 did not consistently
      accord with simple competition: in some preparations depression of the asymptote
      was seen. Schild analysis of data combined from all preparations, regardless of
      the antagonist profile observed, gave an apparent pKB of 8.9 (slope parameter
      0.90). 4. The potency of FPL 67085 was unaffected by the P1-purinoceptor
      antagonist, 8-sulphophenyltheophylline, was similar (IC50 0.6-3.8 nM) in human
      and rat washed platelets or whole blood and, in rat blood, did not change
      following 2-30 min incubation at 37 degrees C. 5. FPL 67085 was a weak (pA50
      approximately 4.2) partial agonist in tissues containing P2X- or P2Y
      purinoceptors, indicating some 30,000 fold selectivity for the P2T-subtype. 6. In
      anaesthetized rats, intravenous infusion of FPL 67085 produced rapidly
      reversible, dose-related inhibition of ADP-induced platelet aggregation measured
      ex vivo (ID50 1.3 micrograms kg-1 min-1) with no significant effect on
      haemodynamics or circulating cell counts. 7. Thus, FPL 67085 is a potent,
      specific and selective inhibitor of ADP-induced platelet aggregation both in
      vitro and in vivo. As such, it represents a novel pharmacological tool to define
      the role of endogenous ADP in thrombosis and the potential of P2T-purinoceptor
      antagonists as a novel class of infusible anti-thrombotic agents for acute use in
      man.

PMID- 7582508
TI  - The in vitro pharmacology of ZM 241385, a potent, non-xanthine A2a selective
      adenosine receptor antagonist.
AB  - 1. This paper describes the in vitro pharmacology of ZM 241385 (4-(2-[7-amino-2
      (2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin- 5-yl amino]ethyl) phenol), a
      novel non-xanthine adenosine receptor antagonist with selectivity for the A2a
      receptor subtype. 2. ZM 241385 had high affinity for A2a receptors. In rat
      phaeochromocytoma cell membranes, ZM 241385 displaced binding of tritiated 5'-N
      ethylcarboxamidoadenosine (NECA) with a pIC50 of 9.52, (95% confidence limits,
      c.l., 9.02-10.02). In guinea-pig isolated Langendorff hearts, ZM 241385
      antagonized vasodilatation of the coronary bed produced by 2-chloroadenosine (2
      CADO) and 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine
      (CGS21680) with pA2 values of 8.57 (c.l., 8.45-8.68) and 9.02 (c.l., 8.79-9.24)
      respectively. 3. ZM 241385 had low potency at A2b receptors and antagonized the
      relaxant effects of adenosine in the guinea-pig aorta with a pA2 of 7.06, (c.l.,
      6.92-7.19). 4. ZM 241385 had a low affinity at A1 receptors. In rat cerebral
      cortex membranes it displaced tritiated R-phenylisopropyladenosine (R-PIA) with a
      pIC50 of 5.69 (c.l., 5.57-5.81). ZM 241385 antagonized the bradycardic action of
      2-CADO in guinea-pig atria with a pA2 of 5.95 (c.l., 5.72-6.18). 5. ZM 241385 had
      low affinity for A3 receptors. At cloned rat A3 receptors expressed in chinese
      hamster ovary cells, it displaced iodinated aminobenzyl-5'-N-methylcarboxamido
      adenosine (AB-MECA) with a pIC50 of 3.82 (c.l., 3.67-4.06). 6. ZM 241385 had no
      significant additional pharmacological effects on the isolated tissues used in
      these studies at concentrations three orders of magnitude greater than those
      which block A2a receptors. At 10 microM it displayed only minor inhibition of the
      bradycardic effects in guinea-pig atria to some concentrations of carbachol. At
      10 microM, ZM 241385 had a small inhibitory effect on relaxant effects of
      isoprenaline in guinea-pig aortae but no effect on sodium nitrite-induced
      relaxation. ZM 241385(100 microM) was without effect on phenylephrine-induced
      tone in guinea-pig aortae.7. ZM 241385 (10 microM) had no inhibitory effect on
      rat hepatocyte phosphodiesterase types I, II, III and IV but caused a small
      inhibition of the calcium calmodulin-activated type I enzyme.8. ZM 241385 is the
      most selective adenosine A2a receptor antagonist yet described and is therefore a
      useful tool for characterization of responses mediated by A2 adenosine receptors.

PMID- 7582512
TI  - Prevention by the cannabinoid antagonist, SR141716A, of cannabinoid-mediated
      blockade of long-term potentiation in the rat hippocampal slice.
AB  - Incubation of rat hippocampal slices in the presence of the synthetic cannabinoid
      (-)-11-OH-delta 8-dimethylheptyl tetrahydrocannabinol (HU-210) (100 nM) prevented
      the induction of long-term potentiation (LTP). Slices co-incubated with both HU
      210 (100 nM) and the cannabinoid antagonist, SR141716A (100 nM), exhibited
      tetanically induced LTP, comparable to control slices. Intriguingly, coincubation
      with HU-210 and SR141716A prevented the induction of the early, short-term phase
      of LTP.

PMID- 7582511
TI  - Potassium currents in human freshly isolated bronchial smooth muscle cells.
AB  - 1. K+ currents were studied in smooth muscle cells enzymatically dissociated from
      human bronchi, by use of the patch-clamp technique. 2. In whole-cell recordings a
      depolarization-induced, 4-aminopyridine (4-AP)-sensitive current was observed in
      only 26 of 155 cells, and in 20 of these 26 cells its amplitude at a test
      potential of 0 mV was less than 100 pA. 3. In the majority of cells
      depolarization to -40 mV or more positive potentials induced a noisy outward
      current which activated within milliseconds and showed almost no inactivation
      even during a 5 s depolarizing voltage step. This current was insensitive to 4-AP
      (up to 5 mM) but was strongly inhibited in the presence of tetraethylammonium
      (TEA, 1 mM), charybdotoxin (ChTX, 100 nM) or iberiotoxin (IbTX, 50 nM) in the
      bath. The same current was also recorded by the nystatin-perforated patch
      technique. 4. Single channels with a conductance of about 210 pS were recorded in
      cell-attached patch, inside-out patch, outside-out patch and whole-cell recording
      configurations. Channel open state probability in inside-out patches was 0.5 at a
      membrane potential of 4 +/- 14 mV (mean +/- s.d., n = 13) mV even with a free
      Ca2+ concentration on the cytosolic side of the patch of less than 0.1 nM. Open
      state probability increased with depolarization and internal Ca2+ concentration.
      Single channels could be reversibly blocked by externally applied TEA, ChTX and
      IbTX. 5. In current-clamp recordings with 100 nM free Ca2+ in the intracellular
      solution both TEA and ChTX caused substantial concentration-dependent
      depolarization. 6. These results suggest that in human bronchial smooth muscle
      cells, in marked contrast to other species, the majority of the outward current
      induced by depolarization is not due to a delayed rectifier,but to the activity
      of a large conductance, ChTX-sensitive K+ channel. The Ca2+- and voltage
      dependency of this channel may well allow a sufficiently high open state
      probability for it to play a partin the regulation of the resting membrane
      potential.

PMID- 7582514
TI  - Activation of the micturition reflex by NK2 receptor stimulation in the
      anaesthetized guinea-pig.
AB  - 1. The mechanisms underlying stimulation of bladder contractions and
      bronchoconstriction by the selective NK2 receptor agonist, [beta-Ala8]NKA(4-10),
      were examined in the anaesthetized guinea-pig. 2. Atropine, alpha,beta-methylene
      ATP and ganglion blocking agents were used to examine the contribution of reflex
      arc activation and/or potentiation of efferent mechanisms to the NK2 receptor
      mediated responses seen in these two tissues. 3. [beta-Ala8]NKA(4-10)-induced
      bronchoconstriction was immediate, dose-dependent and was unaffected by
      pretreatment with ganglion blockers (hexamethonium or chlorisondamine), blockade
      of muscarinic receptors by atropine, or desensitization of P2 purinoceptors by
      alpha,beta-methylene-ATP. 4. At does of 5 micrograms kg-1 and above, [beta
      Ala8]NKA(4-10) induced bladder contractions that appeared to be of an 'all-or
      nothing' nature. These contractions occurred after a delay of 10 to 30 s and were
      often biphasic, comprised of an initial rapid component followed by a slower
      tonic component. 5. Pretreatment of the animals with either atropine or the
      desensitizing purinoceptor agonist alpha,beta-methylene-ATP, resulted in partial
      inhibition of bladder contractile responses to [beta-Ala8]NKA(4-10). The
      combination of atropine and alpha,beta-methylene-ATP pretreatment resulted in
      additive inhibition leading to complete blockade of the response. 6. The bladder
      responses to [beta-Ala8]NKA(4-10) (5 micrograms kg-1) were inhibited by
      pretreatment with the ganglion blockers, hexamethonium and chlorisondamine,
      indicating a preganglionic mechanism of action. 7. These findings demonstrate the
      indirect nature of the bladder contractions induced by activation of NK2
      receptors in the anaesthetized guinea-pig. Contractions occur secondary to the
      release of endogenous cholinergic and NANC transmitters by activation of neuronal
      NK2 receptors located at apreganglionic site, possibly on capsaicin-sensitive
      sensory afferent nerves, where NK2 sites have been demonstrated
      autoradiographically. In contrast, [beta-Ala8]NKA(4- 10)-induced
      bronchoconstriction in the anaesthetized guinea-pig is a direct smooth muscle
      contractile response that is unaffected by ganglionblockade or blockade of
      muscarinic receptors.

PMID- 7582515
TI  - Pharmacological activity of the C-terminal and N-terminal domains of secretory
      leukoprotease inhibitor in vitro.
AB  - 1. In order to characterize the physiological functions of the domain structure
      of secretory leukoprotease inhibitor (SLPI), the biological capacities of half
      length SLPIs, (Ser1-Pro54)SLPI and (Asn55-Ala107)SLPI, were investigated and
      compared with those of full-length SLPI. 2. The activities of these inhibitors
      against several serine proteases were determined using synthetic chromogenic
      substrates. The inhibitory capacity of the C-terminal domain, (Asn55-Ala107)SLPI,
      was as strong as that of full-length SLPI against human neutrophil elastase (NE),
      cathepsin G and chymotrypsin. It possessed less trypsin inhibitory activity than
      intact SLPI. For the N-terminal domain of SLPI, (Ser1-Pro54)SLPI, no inhibitory
      activity could be detected against the serine proteases tested in this study. 3.
      The inhibitory activity of (Asn55-Ala107)SLPI against the proteolysis of the
      natural substrates elastin and collagen by NE was comparable with that of full
      SLPI (elastin, IC50 = 907 +/- 31 nM for SLPI, 767 +/- 33 nM for (Asn55
      Ala107)SLPI; collagen, IC50 = 862 +/- 36 nM for SLPI, 727 +/- 47 nM for (Asn55
      Ala107)SLPI). 4. The binding affinities of full- and half-length SLPIs for
      heparin were measured by affinity column chromatography. Full-length SLPI showed
      high affinity for heparin while the binding capacities of both half-length SLPIs
      were lower. (Concentration of NaCl for elution, 0.45 M for SLPI, 0.24 M for (Ser1
      Pro54)SLPI, 0.27 M for (Asn55-Ala107)SLPI). 5. The effects of full-SLPI and
      (Asn55-Ala107)SLPI on blood coagulation were measured using the activated partial
      thromboplastin time (APTT). Full-length SLPI prolonged clotting time dose
      dependently(1.25, 2.5 and 5.0 microM), whereas (Asn55-AlalO7)SLPI had no effect
      even at the highest concentration.6. In conclusion, the C-terminal domain of SLPI
      is a promising candidate for the treatment of inflammatory diseases in which
      participation of neutrophil proteases has been suggested.

PMID- 7582513
TI  - Effect of illuminated nifedipine, a potent antioxidant, on intestinal and
      vascular smooth muscles.
AB  - 1. The effects of nifedipine (Nif) and its illuminated nitroso product
      nitrosopine (NTP) were investigated on lipid peroxidation, KCl elevated smooth
      muscle tension, and ionic currents of single smooth muscle cells. 2. Illumination
      of Nif at 400-700 nm within 24-48 h changed it completely to a potent
      antioxidant, NTP. 3. Nif relaxed the KCl-induced contractions of guinea-pig
      taenia caeci and rat aorta and reduced the amplitude of the evoked inward Ca2+
      current of taenia caeci cells in a concentration-dependent manner. NTP (up to 100
      microM) was ineffective in this respect. Pretreatment by NTP (10 microM) did not
      affect the actions of Nif. 4. The evidence suggests that NTP, generated by day
      light illumination from Nif, exerts antioxidant activity but is devoid of voltage
      dependent Ca2+ channel (VDC) blocking property and does not interfere with the
      action of Nif on the smooth muscle cell membrane VDC.

PMID- 7582517
TI  - A novel receptor for diadenosine polyphosphates coupled to calcium increase in
      rat midbrain synaptosomes.
AB  - 1. Diadenosine polyphosphates, Ap4A and Ap5A, as well as ATP, alpha,beta-MeATP
      and ADP-beta-S, were able to elicit variable intrasynaptosomal Ca2+ increases in
      rat midbrain synaptic terminals. The origin of the Ca2+ increment was the extra
      synaptosomal space since the elimination of extracellular Ca2+ abolished the
      effect of all the agonists. 2. The P2-purinoceptor antagonist, suramin, did not
      affect the Ca(2+)-increase evoked by diadenosine polyphosphates but dramatically
      blocked the Ca2+ entry induced by ATP and its synthetic analogues. 3. The actions
      of Ap5A and ATP on the intrasynaptosomal Ca2+ increase did not cross-desensitize.
      4. Concentration-response studies for diadenosine polyphosphates showed pD2
      values of 54.5 +/- 4.2 microM and 55.6 +/- 3.8 microM for Ap4A and Ap5A,
      respectively. 5. The entry of calcium induced by diadenosine polyphosphates could
      be separated into two components. The first represented a selective voltage
      independent Ca2+ entry; the second, a sustained phase which was voltage
      dependent. 6. Studies on the voltage-dependent Ca(2+)-channels involved in the
      effects of the diadenosine polyphosphates, demonstrated that omega-conotoxin G-VI
      A inhibited the sustained Ca(2+)-entry, suggesting the participation of an N-type
      Ca(2+)-channel. This toxin was unable to abolish the initial cation entry induced
      by Ap4A or Ap5A. omega-Agatoxin IV-A, tetrodotoxin, or nifedipine did not inhibit
      the effects of the diadenosine polyphosphates. 7. The effect of ATP on Ca(2+)
      entry was abolished by nifedipine and omega-conotoxin G-VI-A, suggesting the
      participation of L- and N-type Ca(2+)-channels in the response to ATP. 8. These
      data suggest that Ap4A, Ap5A and ATP activate the same intracellular Ca2+ signal
      through different receptors and different mechanisms. Ap4A and Ap5A induce a more
      selective Ca2+-entry in a voltage-independent process. This is the first time
      that a selective action of diadenosine polyphosphate through receptors other than
      P1 and P2-purinoceptors has been described.

PMID- 7582518
TI  - Mode of action of thrombin in the rabbit aorta.
AB  - 1. Thrombin is a vasoactive protease that elicits the contraction of the rabbit
      aorta by activating a G-protein coupled receptor through cleavage of its N
      terminal extracellular domain. Synthetic peptides corresponding to the newly
      exposed N-terminus, following thrombin cleavage, have been shown to reproduce
      some of the activities of thrombin in the rabbit aorta. 2. Intracellular pathways
      involved in the contractile response of the rabbit aorta to thrombin and
      synthetic peptides were examined by use of a series of inhibitors. A similar
      method was applied to characterize the mitogenic effect of thrombin on cultured
      smooth muscle cells (SMCs) derived from the same tissue. 3. Results from this
      study indicate that the contractile response of the rabbit aorta to thrombin is
      dependent on the activation of protein kinase C (PKC) and independent of
      extracellular calcium. The contractile response to thrombin can be fully
      reproduced by peptide agonists related to the N-terminal receptor sequence.
      However, subtle differences seem to exist between the mechanism of the
      contractile effect of thrombin and of the synthetic peptides, as both PKC
      activation and extracellular calcium were found to participate in the contractile
      effect of the synthetic peptides. 4. In cultured SMCs, both thrombin and the
      synthetic peptides increased inositol phosphate turnover; however, only thrombin
      elicited a mitogenic effect, which occurs at thrombin concentrations well below
      those needed to increase inositol phosphate turnover significantly. Activation of
      a tyrosine kinase pathway is involved in the mitogenic effect of thrombin on
      aortic SMCs. 5. Altogether these results suggest the existence of subtle
      differences between the mode of action of thrombin and of synthetic peptides
      related to the N-terminal thrombin receptor sequence, in the rabbit aorta.

PMID- 7582520
TI  - Inhibition of bronchoconstriction by pituitary adenylate cyclase activating
      polypeptide (PACAP 1-27) in guinea-pigs in vivo.
AB  - 1. We studied the inhibitory effect of pituitary adenylate cyclase activating
      polypeptide (PACAP 1-27) on the increase in total pulmonary resistance (RL)
      caused either by allergen or histamine in anaesthetized, ventilated guinea-pigs.
      2. PACAP 1-27 given via i.v. infusion (0.045-4.5 nmol kg-1 min-1) dose
      dependently reduced the increase in RL caused by inhaled ovalbumin and histamine.
      At the highest dose, PACAP 1-27 prevented the increase in RL caused by ovalbumin
      and histamine completely. Infusion of PACAP 1-27 and the beta 2-adrenoceptor
      agonist, salbutamol (0.045-4.5 nmol kg-1 min-1) inhibited the increase in RL
      similarly, but salbutamol increased the heart rate more than PACAP 1-27. 3. PACAP
      1-27 and salbutamol given via inhaled aerosol (0.1 mM, 20 breaths) significantly
      reduced the increase in RL caused by histamine infused i.v., whereas aerosolised
      sterile saline did not. Both PACAP 1-27 and salbutamol caused bronchodilator
      effects within 1 min of drug inhalation and these effects remained throughout the
      20 min of study. 4. Because PACAP 1-27 produced significant bronchodilatation and
      rapid onset of sustained action in vivo and without pronounced cardiovascular
      side effects, we conclude that this peptide may have therapeutic potential as a
      bronchodilator.

PMID- 7582519
TI  - Actions of the insecticide fipronil, on dieldrin-sensitive and- resistant GABA
      receptors of Drosophila melanogaster.
AB  - 1. Blocking actions of the novel insecticide, fipronil, were examined on GABA
      responses recorded from Xenopus oocytes expressing either wild type (dieldrin
      sensitive) or mutant (dieldrin-resistant) forms of the Drosophila melanogaster
      GABA-gated chloride channel homo-oligomer, RDL (the product of the resistance to
      dieldrin locus: Rdl). 2. In the case of the wild type receptor, fipronil blocked
      GABA-induced currents inducing both a shift to the right in the GABA dose
      response curve and depressing the maximum amplitude of responses to GABA. The
      potency of fipronil was dependent on the GABA concentration but was unaffected by
      membrane potential. 3. Mutant RDL GABA-receptors, which have a naturally
      occurring amino acid substitution (A302-->S) in the putative ion-channel lining
      region, conferring resistance to dieldrin and picrotoxinin, were markedly less
      sensitive to fipronil than the wild-type receptors. 4. Fipronil antagonism is
      qualitatively similar to that produced by the structurally distinct compound,
      picrotoxinin. As the mutation A302-->S reduces the potency of both fipronil and
      picrotoxinin, homooligomeric RDL receptors should facilitate detailed studies of
      the molecular basis of convulsant/insecticide antagonist actions on GABA
      receptors.

PMID- 7582521
TI  - Attenuation of adrenomedullin-induced renal vasodilatation by NG-nitro L-arginine
      but not glibenclamide.
AB  - 1. The present study was conducted in order to elucidate the in vivo contribution
      of nitric oxide (NO) and the glibenclamide-sensitive potassium channel in the
      renal action of adrenomedullin in anaesthetized dogs. 2. Intrarenal arterial
      infusion of adrenomedullin (20 ng kg-1 min-1) elicited a pronounced increase in
      renal blood flow with no changes in systemic blood pressure. The renal
      vasodilator action of adrenomedullin was markedly attenuated by pretreatment with
      NG-nitro L-arginine (L-NOARG), but this was reversed by continuous infusion of L
      arginine. 3. Pretreatment with glibenclamide almost completely blocked the renal
      vasodilatation induced by lemakalim, but had no effect on the renal vasodilator
      and diuretic action of adrenomedullin. 4. Intrarenal arterial infusion of
      adrenomedullin induced diuresis and natriuresis. Diuretic and natriuretic action
      of adrenomedullin was also attenuated by L-NOARG. L-Arginine partly reversed the
      effect of L-NOARG and adrenomedullin-induced diuresis and natriuresis. 5. These
      data indicate that the in vivo renal vasodilator action of adrenomedullin is
      mediated by the release of NO. The glibenclamide-sensitive potassium channel is
      not involved in the renal action of adrenomedullin, at least, not in
      anaesthetized dogs. Since the inhibition of L-NOARG of adrenomedullin-induced
      diuresis occurred concomitantly with the attenuation of the renal vasodilator
      action of adrenomedullin, direct involvement of NO in adrenomedullin-induced
      diuresis remains to be established.

PMID- 7582516
TI  - Substance P-induced relaxation and hyperpolarization in human cerebral arteries.
AB  - 1. Vascular effects of substance P were studied in human isolated pial arteries
      removed from 14 patients undergoing cerebral cortical resection. 2. Substance P
      induced a concentration-dependent relaxation in the presence of indomethacin. No
      relaxation was seen in arteries where the endothelium had been removed. 3. N
      omega-nitro-L-arginine (L-NOARG, 0.3 mM) abolished the relaxation in arteries
      from six patients. The relaxation was only partially inhibited in the remaining
      eight patients, the reduction of the maximum relaxation being less than 50% in
      each patient. 4. The L-NOARG-resistant relaxation was abolished when the external
      K+ concentration was raised above 30 mM. 5. Substance P caused a smooth muscle
      hyperpolarization (in the presence of L-NOARG and indomethacin), but only when
      the artery showed an L-NOARG-resistant relaxation. 6. The results indicate that
      nitric oxide is an important mediator of endothelium-dependent relaxation in
      human cerebral arteries. Furthermore, another endothelium-dependent pathway,
      causing hyperpolarization and vasodilatation, was identified in arteries from
      more than half the population of patients.

PMID- 7582523
TI  - Labelling with [125I]-SB 207710 of a small 5-HT4 receptor population in piglet
      right atrium: functional relevance.
AB  - 1. We investigated the affinity of SB 207710 for sinoatrial 5-HT4 receptors and
      the density of right atrial 5-HT4 receptors with [125I]-SB 207710 in right atria
      of new-born piglets. 2. SB 207710 (1-100 nM) antagonized the 5-HT-evoked
      tachycardia surmountably with a pKB of 9.8. 3. [125I]-SB 207710 (5-1500 pM)
      labelled a small population of saturable binding sites with a pKD of 10.1 and
      with 5-HT4 receptor characteristics. The density of atrial binding sites with 5
      HT4 receptor characteristics was 174 and 22 times lower respectively than those
      of atrial beta 1- and beta 2-adrenoceptors, labelled with (-)-[125I]
      cyanopindolol. 4. We suggest that the small 5-HT4 receptor population may in part
      explain why the maximal tachycardia caused by 5-HT is smaller than that caused by
      catecholamines.

PMID- 7582522
TI  - Characterization of acute homologous desensitization of mu-opioid receptor
      induced currents in locus coeruleus neurones.
AB  - 1. Acute homologous desensitization of mu-opioid receptor-induced currents was
      pharmacologically characterized in locus coeruleus (LC) neurones by use of
      intracellular and whole cell recording in superfused brain slices. 2. Following
      desensitization of opioid receptors by perfusion with a high concentration of
      [Met5] enkephalin (ME) for 5 min, there was a reduction in the maximum response
      and a rightward shift of the concentration-response curves for ME, [D-Ala2, N
      MePhe4, Gly-ol]enkephalin (DAMGO) and normorphine. 3. By simultaneously fitting
      the operational model to the paired pre- and post-desensitization concentration
      response data for each agonist, estimates of the level of desensitization were
      obtained. The values obtained for the three agonists (between 88% and 96%) were
      similar and did not vary according to the efficacy of the agonist used. 4. Use of
      whole cell patch recording techniques caused a slow rundown in the amplitude of
      ME currents (approx. 40% reduction over 60 min) but did not greatly affect the
      expression of acute desensitization of opioid currents. 5. When included in the
      patch recording solution, the phosphatase inhibitors, microcystin (50 nM-4
      microM) and okadaic acid (1 microM) had no effect on the induction of
      desensitization or the normal ability of opioid or alpha 2-adrenoceptors to
      produce currents. Microcystin decreased the rate of recovery of the ME (300 nM)
      currents following desensitization; however, okadaic acid had little effect on
      the rate of recovery from desensitization. 6. Strong calcium buffering with BAPTA
      (10-20 mM) had no effect on desensitization or the recovery from desensitization.
      6. Strong calcium buffering with BAPTA (10-20 mM) had no effect on
      desensitization or the recovery from desensitization.7 These results suggest that
      acute homologous desensitization of micro-opioid receptors in LC neurones entails
      a rapid loss of responsiveness that involves a majority of the receptor
      population. The mechanism by which desensitization is reversed may involve a non
      calcium-dependent protein phosphatase but the processess that cause
      desensitization remain unclear.

PMID- 7582524
TI  - Ca(2+)-dependent and -independent mechanism of cyclic-AMP reduction: mediation by
      bradykinin B2 receptors.
AB  - 1. Bradykinin caused a transient reduction of about 25% in the cyclic AMP level
      in forskolin prestimulated DDT1 MF-2 smooth muscle cells (IC50: 36.4 +/- 4.9 nM)
      and a pronounced, sustained inhibition (40%) of the isoprenaline-stimulated
      cyclic AMP level (IC50: 37.5 +/- 1.1 nM). 2. The Ca2+ ionophore, ionomycin,
      mimicked both the bradykinin-induced transient reduction in the forskolin
      stimulated cyclic AMP level and the sustained reduction in the isoprenaline
      stimulated cyclic AMP level. 3. The Ca(2+)-dependent effect on cyclic AMP induced
      by bradykinin was mediated solely by Ca2+ release from internal stores, since
      inhibition of Ca2+ entry with LaCl3 did not reduce the response to bradykinin. 4.
      The involvement of calmodulin-dependent enzyme activities, protein kinase C or an
      inhibitory GTP binding protein in the bradykinin-induced responses was excluded
      since a calmodulin inhibitor, calmidazolium, a PKC inhibitor, staurosporine and
      pertussis toxin, respectively did not affect the decline in the cyclic AMP level.
      5. Bradykinin enhanced the rate of cyclic AMP breakdown in intact cells, which
      effect was not mimicked by ionomycin. This suggested a Ca(2+)-independent
      activation of phosphodiesterase activity by bradykinin in DDT1 MF-2 cells. 6. The
      bradykinin B1 receptor agonist, desArg9-bradykinin, did not affect cyclic AMP
      formation in isoprenaline prestimulated cells, while the bradykinin B2 receptor
      antagonists, Hoe 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-BK) and D-Arg[Hyp3, Thi5,8,
      D-Phe7]-BK completely abolished the bradykinin response in both forskolin and
      isoprenaline prestimulated cells. 7. Bradykinin caused an increase in
      intracellular Ca2+, which was antagonized by the bradykinin B2 receptor
      antagonists, Hoe 140 and D-Arg[Hyp3, Thi5,8, D-Phe7]-BK. The bradykinin B2
      receptor agonist,desArg9-bradykinin, did not evoke a rise in cytoplasmic Ca2 .8.
      It is concluded, that stimulation of bradykinin B2 receptors causes a reduction
      in cellular cyclic AMP in DDT1, MF-2 cells. This decline in cyclic AMP is partly
      mediated by a Ca2+/calmodulin independent activation of phosphodiesterase
      activity. The increase in [Ca2+], mediated by bradykinin B2 receptors inhibited
      forskolin- and isoprenaline-activated adenylyl cyclase differently, most likely
      by interfering with different components of the adenylyl cyclase signalling
      pathway.

PMID- 7582525
TI  - A role for mast cells in adenosine A3 receptor-mediated hypotension in the rat.
AB  - 1. The adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA)
      induces hypotension in the anaesthetized rat. The present experiments were
      carried out to explore the role of mast cells in the response. 2. Intravenous
      injection of APNEA (1-30 micrograms kg-1 to rats in which the A3 receptor
      mediated response had been isolated by pretreatment with 8-(p-sulphophenyl)
      theophylline (8-SPT)), induced dose-related falls in blood pressure accompanied
      at higher doses by small falls in heart rate. Responses to the mast cell
      degranulating agent, compound 48/80 (10-300 micrograms kg-1, i.v.) were
      qualitatively similar to those to APNEA. 3. Pretreatment with sodium cromoglycate
      (0.25-20 mg kg-1, i.v.) induced dose-related, although incomplete, blockade of
      the hypotensive responses to APNEA. At 20 mg kg-1, sodium cromoglycate also
      inhibited the cardiovascular response to compound 48/80 but had no effects on
      those to the selective A1 receptor agonist, N6-cyclopentyladenosine (CPA) or the
      selective A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylamino]-5'-N
      ethylcarboxamidoadenosine (CGS 21680). Lodoxamide (0.01-20 mg kg-1) also blocked
      selectively but incompletely the response to APNEA. 4. The cardiovascular
      responses to compound 48/80 (10-300 micrograms kg-1, i.v.) were markedly
      suppressed in animals which had received repeated doses of the compound by the
      intraperitoneal route. Similarly APNEA was essentially devoid of cardiovascular
      activity in such preparations. In contrast, responses to CPA were similar in
      animals treated repeatedly with compound 48/80 to those obtained in control
      animals. 5. Plasma and serum histamine concentrations were markedly increased
      associated with the pronounced hypotensive responses induced by intravenous
      injections of APNEA (30 or 100 microg kg-1) in the presence of 8-SPT, or compound
      48/80 (300 microg kg-1).6. Taken together the data implicate the mast cell in a
      key role in adenosine A3 receptor-mediated hypotension in the anaesthetized rat.

PMID- 7582526
TI  - Potentiation, activation and blockade of GABAA receptors of clonal murine
      hypothalamic GT1-7 neurones by propofol.
AB  - 1. The actions of GABA and the intravenous general anaesthetic propofol (2,6
      diisopropylphenol) on GABAA receptors of self-replicating GT1-7 hypothalamic
      neurones were investigated by the patch clamp technique. 2. GABA (1 microM-1 mM)
      dose-dependently activated inward currents with an EC50 of 27 microM, recorded
      from whole cells voltage-clamped at -60 mV. GABA (100 microM)-activated currents
      reversed at the Cl-equilibrium potential. 3. Propofol (0.1-100 microM) dose
      dependently potentiated GABA (100 microM)-evoked currents with an EC50 of 5
      microM. 4. In the absence of GABA, propofol (10 microM-1 mM) activated small
      inward currents with a reversal potential similar to the Cl- equilibrium
      potential. The peak current amplitudes activated by propofol were only 31% of
      those activated by GABA in the same cells. 5. Like GABA (100 microM)-activated
      currents, propofol (100 microM)-activated currents were inhibited by the GABAA
      receptor antagonist, bicuculline (10 microM) and were abolished by Zn2+ (100
      microM). 6. Propofol (10, 30 and 100 microM) dose-dependently activated currents
      in the absence of GABA. However, the peak amplitude of currents activated by
      propofol declined with concentrations > 100 microM. The cessation of application
      of a high dose of propofol (1 mM) was associated with a current 'surge'. 7. The
      surge current, seen after application of propofol (1 mM), had a reversal
      potential similar to the Cl- equilibrium potential. The ratio between peak
      current amplitude in the presence of propofol (1 mM) and surge current amplitude
      after propofol application, were not dependent on holding potential. Thus,it is
      unlikely that the surge current represents reversal of a voltage-dependent block
      of GABAA receptors by propofol.8. The amplitude of the surge current exceeded the
      amplitude of the initial propofol (1 mM)-evoked current following brief
      applications, but declined after prolonged applications of the drug.9. The
      observed modulatory actions of propofol may be due to separate potentiation,
      activation and inhibitory sites for this anaesthetic agent on GT1-7 cell GABAA
      receptors.

PMID- 7582527
TI  - Application of a model to explore interspecies differences in acetylcholine M
      receptor-stimulated gastric acid secretion.
AB  - 1. Concentration-effect curves were obtained, in the absence and presence of
      histamine H2-receptor blockade, to 5-methylfurmethide (5-MeF) and McN-A 343, high
      efficacy and low efficacy acetylcholine (ACh) M-receptor agonists, respectively,
      in isolated stomach preparations from the mouse and immature rat and guinea-pig.
      2. In the immature guinea-pig assay, the responses to 5-MeF and McN-A 343 were
      abolished by histamine H2-receptor blockade suggesting that the responses were
      totally dependent upon gastric mucosal histamine. However, in the mouse and
      immature rat assays, although the histamine H2-receptor antagonists produced
      small but significant rightward shifts and, in some cases, depression of the
      maximum of the agonist concentration-effect curves, a significant secretory
      response remained, presumed to be due to direct stimulation of oxyntic cells. 3.
      Previously, by assuming that the histamine H2-receptor blockade alters the mode
      of agonist-stimulated acid secretion from mainly an indirect action mediated by
      histamine release to direct stimulation of the oxyntic cell, we applied an
      operational model of agonism to similar data obtained in the mouse preparation.
      In that study we were able to account for the behaviour of 5-MeF and McN-A 343 by
      assuming that the agonists expressed 6 fold higher efficacy, tau in the
      operational model of agonism, at ACh M-receptors on the histamine-releasing cells
      than on the oxyntic cells. In this study it was possible to account for the
      variation in the behaviour of the agonists both between and within assays by
      simply varying the efficacy expressed by the agonists at each of the cells in the
      model. The efficacy variation could be due to receptor concentration variation.4.
      The data and analysis are discussed in terms of contemporary models for the role
      of histamine in the regulation of gastric acid secretion.

PMID- 7582528
TI  - Selective inhibition by barbiturates of the synthesis of endothelium-derived
      hyperpolarizing factor in the rabbit carotid artery.
AB  - 1. Several lines of evidence suggest that both volatile and intravenous
      anaesthetics may interfere with the synthesis and release of endothelium-derived
      vasoactive factors. We have investigated the effects of three different
      barbiturates on the release of nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor (EDHF) in phenylephrine (1 microM)-preconstricted,
      endothelium-intact ring segments of the rabbit carotid artery. The segments were
      pretreated with the cyclo-oxygenase inhibitor, diclofenac (1 microM), to prevent
      the formation of vasoactive prostanoids, such as prostacyclin (PGI2). 2.
      Acetylcholine (ACh) elicited a concentration-dependent relaxation (EC50 0.15
      microM) in control segments which was not significantly different from the
      relaxant responses of segments pretreated with methohexitone (0.03-0.3 mM),
      phenobarbitone (0.1-0.3 mM) or thiopentone (0.1-0.3 mM). 3. Inhibition of NO
      synthesis with NG-nitro-L-arginine (0.1 mM) significantly reduced the maximum
      relaxant response to ACh from 96 to 40%. This NO/PGI2-independent relaxation
      appeared to be mediated by the release of EDHF, since it was strongly diminished
      in the presence of the K+Ca inhibitors, tetrabutylammonium (1-3 mM) and
      charybdotoxin (10 nM), following preconstriction with potassium calcium (40 mM)
      or removal of the endothelium. Thiopentone or methohexitone markedly attenuated
      the EDHF-mediated relaxant response to ACh, while phenobarbitone had no effect.
      The endothelium-independent relaxation elicited by sodium nitroprusside (0.01-10
      microM), on the other hand, was only marginally affected by these anaesthetics.
      4. The cytochrome P450 inhibitor, clotrimazole (3-100 microM), mimicked the
      inhibitory effect of thiopentone and methohexitone on the NO/PGI2-independent
      relaxant response to ACh. Moreover the cytochrome P450-catalyzed O-dealkylation
      of 7-ethoxycoumarin by rabbit liver microsomes was inhibited in the presence of
      thiopentone or methohexitone (0.3-1 mM), while phenobarbitone was without
      effect.5. These findings suggest that thiopentone and methohexitone selectively
      attenuate the EDHF-mediated relaxant response to ACh in the rabbit carotid
      artery, presumably by interfering with its synthesis from arachidonic acid via
      the cytochrome P450 epoxygenase pathway.

PMID- 7582529
TI  - Further evidence from functional studies for somatostatin receptor heterogeneity
      in guinea-pig isolated ileum, vas deferens and right atrium.
AB  - 1. Somatostatin (SRIF) causes a concentration-dependent inhibition of
      neurotransmission in guinea-pig ileum and vas deferens as well as negative
      inotropy in guinea-pig isolated right atrium. The SRIF receptors mediating these
      effects have now been further characterized by use of the peptides BIM-23027, BIM
      23056 and L-362855, reported as selective for the recombinant SRIF receptor
      types, sst2, sst3 and sst5, respectively. 2. BIM-23027 was a highly potent
      agonist at causing an inhibition of neurotransmission in the guinea-pig ileum
      (EC50 value 1.9 nM), being about 3 times more potent than SRIF (EC50 value 6.8
      nM). In contrast, in both guinea-pig vas deferens and right atrial preparations,
      BIM-23027 was a relatively weak agonist being at least 30-100 times weaker than
      SRIF. In guinea-pig atria, BIM-23027 (3 microM) antagonized the negative
      inotropic action of SRIF28 (apparent pKB = 5.9 +/- 0.1) but had no effect on the
      negative inotropic action of cyclohexyladenosine. 3. The inhibitory effect of BIM
      23027 in the guinea-pig ileum was readily desensitized. Prior exposure to BIM
      23027 (0.3 microM) markedly attenuated the inhibitory effect of SRIF but had no
      effect on the inhibitory action of clonidine suggesting that BIM-23027 and SRIF
      act via a common receptor mechanism. 4. L-362855 caused a concentration-dependent
      inhibition of neurotransmission in both the guinea-pig ileum and vas deferens as
      well as causing negative inotropy in the guinea-pig atrium but was at least 30
      100 times weaker than SRIF. In guinea-pig isolated atria, L-362855 (3 microM) did
      not antagonize the negative inotropic action of SRIF28. 5. BIM-23056 in
      concentrations up to 1 microM was inactive as an agonist in guinea-pig isolated
      ileum, vas deferens and atrium and did not antagonize the inhibitory actions of
      SRIF in any of these preparations.6. The results from this study support our
      previous contention that the sst2 receptor type mediates inhibition of
      neurotransmission by SRIF in the guinea-pig ileum. The SRIF receptor type
      mediating inhibition of neurotransmission in the guinea-pig vas deferens appears
      different, but similar, to that mediating negative inotropy in the atrium.
      However the characteristics of these latter receptors appear different from that
      of the recombinant sst2, sst3 and sst5 receptors for SRIF described for rat and
      man.

PMID- 7582530
TI  - Characterization of an alpha 1D-adrenoceptor mediating the contractile response
      of rat aorta to noradrenaline.
AB  - 1. The affinities of a number of alpha 1-adrenoceptor antagonists were determined
      by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors
      (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha
      1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affinity
      estimates for these compounds were also determined from noradrenaline-mediated
      contractions of rat aorta. 2. BMY 7378 displayed high affinity for cloned human
      alpha 1D-adrenoceptors (pKi = 8.2 +/- 0.10) and was selective over alpha 1A (pKi
      = 6.2 +/- 0.10) and alpha 1B subtypes (6.7 +/- 0.11). WB 4101, benoxathian and
      phentolamine displayed high affinity for alpha 1A and alpha 1D adrenoceptors
      compared to the alpha 1B subtype. Spiperone displayed high affinity and
      selectivity for alpha 1B adrenoceptors (pKi 8.8 +/- 0.16). 5-Methyl-urapidil was
      selective for cloned alpha 1A adrenoceptors. 3. Comparative binding affinities
      (pKi) for compounds at cloned human and rat1D adrenoceptors were almost identical
      (r = 0.99, slope = 1.08). 4. Prazosin, doxazosin and 5-methyl-urapidil were
      potent, competitive antagonists of noradrenaline-mediated contractions of rat
      aorta (pA2 values of 9.8, 8.8 and 7.8 respectively). The selective alpha 1D
      antagonist BMY 7378 was also a potent antagonist on rat aorta (pKB = 8.3 +/- 0.1)
      but the interaction of this compound was not consistent with competitive
      antagonism at a single population of receptors. 5. Functional affinities for
      compounds determined against noradrenaline-mediated contractions of rat aorta
      correlated well with binding affinities at cloned alpha 1D-adrenoceptors (r =
      0.96), but not with alpha 1A (r = 0.61) or alpha 1B (r = 0.46) subtypes. 6.
      Noradrenaline-mediated contractions of rat aorta were sensitive to the alkylating
      effects of chlorethylclonidine (CEC). CEC (10 microM) caused a small rightward
      shift in the noradrenaline concentration-response curve. CEC at 100 microM caused
      a further shift and suppression of the maximum response to noradrenaline.7. The
      results of this study suggest that noradrenaline predominantly, but not
      exclusively, mediates contraction of rat aorta through the activation of an
      alphalD-adrenoceptor.

PMID- 7582533
TI  - Effects of WIN 64338, a nonpeptide bradykinin B2 receptor antagonist, on guinea
      pig trachea.
AB  - We investigated the effect of the nonpeptide bradykinin receptor antagonist, [[4
      [[2-[[bis(cyclohexylamino)methylene] amino]-3-(2-naphthalenyl) 1-oxopropyl]amino]
      phenyl]-tributyl, chloride, monohydrochloride (WIN 64338), on [3H]-bradykinin
      binding and on bradykinin-induced contraction of the guinea-pig trachea. This non
      peptide bradykinin receptor antagonist inhibited [3H]-bradykinin binding with a
      nanomolar range of affinity, Ki = 50.9 +/- 19 nM and inhibited bradykinin-induced
      contraction in a non-competitive manner with a KB value of 6.43 10(-8) +/- 2.34
      10(-8) M.

PMID- 7582531
TI  - Thapsigargin- and cyclopiazonic acid-induced endothelium-dependent
      hyperpolarization in rat mesenteric artery.
AB  - 1. The present study was designed to determine whether putative, selective
      inhibitors of the Ca(2+)-pump ATPase of endoplasmic reticulum, thapsigargin (TSG)
      and cyclopiazonic acid (CPA), induce endothelium-dependent hyperpolarization in
      the rat isolated mesenteric artery. The membrane potentials of smooth muscle
      cells of main superior mesenteric arteries were measured by the microelectrode
      technique. 2. In tissues with endothelium, TSG (10(-8)-10(-5) M) caused sustained
      hyperpolarization in a concentration-dependent manner. In tissues without
      endothelium, TSG did not cause any change in membrane potential. CPA (10(-5) M)
      also hyperpolarized the smooth muscle membrane, an effect that was endothelium
      dependent and long-lasting. 3. The hyperpolarizing responses to these agents were
      not affected by indomethacin or NG-nitro-L-arginine (L-NOARG). 4. In Ca(2+)-free
      medium, neither TSG nor CPA elicited hyperpolarization, in contrast to
      acetylcholine which generated a transient hyperpolarizing response. 5. In rings
      of mesenteric artery precontracted with phenylephrine, TSG and CPA produced
      endothelium-dependent relaxations. L-NOARG significantly inhibited the
      relaxations to these agents, but about 40-60% of the total relaxation was
      resistant to L-NOARG. The L-NOARG-resistant relaxations were abolished by
      potassium depolarization. 6. These results indicate that TSG and CPA can cause
      endothelium-dependent hyperpolarization in rat mesenteric artery possibly by
      releasing endothelium-derived hyperpolarizing factor and that membrane
      hyperpolarization can contribute to the endothelium-dependent relaxations to
      these agents. The mechanism of hyperpolarization may be related to increased Ca2+
      influx into endothelial cells triggered by depletion of intracellular Ca2+ stores
      due to inhibition of endoplasmic reticulum Ca(2+)-pump ATPase activity.

PMID- 7582534
TI  - Nitroglycerin-induced direct protection of the ischaemic myocardium in isolated
      working hearts of rats with vascular tolerance to nitroglycerin.
AB  - We investigated whether nitroglycerin (NTG) was able to produce an anti-ischaemic
      effect in isolated working hearts of rats with vascular tolerance to NTG. Hearts
      isolated from tolerant and non-tolerant rats were subjected to 10 min coronary
      occlusion in the presence of 10(-7) M NTG and/or its solvent. NTG alleviated
      ischaemia-induced deterioration of cardiac function and decreased lactate
      dehydrogenase release whilst having no effect on coronary flow nor the area of
      the ischaemic zone both in hearts isolated from NTG-tolerant and non-tolerant
      rats. The magnitude of the effect was similar in the two groups. These results
      suggest that the anti-ischaemic effect of NTG involves direct myocardial
      mechanisms independent of its vascular action and that vascular tolerance to NTG
      does not affect this direct protective action.

PMID- 7582532
TI  - Differential sensitivity of basal and acetylcholine-stimulated activity of nitric
      oxide to destruction by superoxide anion in rat aorta.
AB  - 1. In this study we compared the ability of superoxide anion to destroy the
      relaxant activity of basal and acetylcholine (ACh)-stimulated activity of NO in
      isolated rings of rat aorta. 2. Superoxide dismutase (SOD, 1-300 u ml-1) induced
      a concentration-dependent relaxation of phenylephrine (PE)-induced tone in
      endothelium-containing rings which was blocked by NG-nitro-L-arginine (L-NOARG,
      30 microM), but had no effect on endothelium-denuded rings. It was likely
      therefore that the relaxant action of SOD resulted from protection of basally
      produced NO from destruction by superoxide anion, generated either within the
      tissue or in the oxygenated Krebs solution. 3. In contrast, a concentration of
      SOD (50 u ml-1) which produced almost maximal enhancement of basal NO activity,
      had no effect on ACh (10 nM-3 microM)-induced relaxation. 4. In the presence of
      catalase (3000 u ml-1) to prevent the actions of hydrogen peroxide, superoxide
      anion generation using hypoxanthine (HX, 0.1 mM)/xanthine oxidase (XO, 16 mu ml
      1) produced an augmentation of PE-induced tone in endothelium-containing but not
      endothelium-denuded rings. This was likely to have resulted from removal of the
      tonic vasodilator action of basally-produced NO by superoxide anion, since it was
      blocked in tissues treated with SOD (250 u ml-1), NG-monomethyl-L-arginine (L
      NMMA, 30 microM) or L-NOARG (30 microM). Pyrogallol (0.1 mM) had a similar action
      to HX/XO, but produced an additional augmentation of tone by an endothelium
      independent mechanism. 5. In contrast to their ability to destroy almost
      completely the basal activity of NO, HX (0.1 mM)/XO(16 mu ml-1) and pyrogallol
      (0.1 mM) had no effect on ACh-induced relaxation at any concentration. An
      increase in the concentration of HX to 1 mM or pyrogallol to 0.3 mM did, however,
      lead to a profound decrease in the magnitude and time course of ACh-induced
      relaxation at all concentrations.6. Treatment with diethyldithiocarbamate (DETCA,
      0.1 mM, 1 h) to inhibit endogenous Cu-Zn SOD,augmented PE-induced tone in
      endothelium-containing rings and abolished the ability of HX (0.1 mM)/XO (16 mu
      ml-1) and L-NMMA (30 microM) to augment tone. It was likely that DETCA had led to
      the destruction of basal NO activity by increasing superoxide anion levels since
      its actions were reversed by exogenous SOD (10-300 upsilon ml-1).7. In contrast
      to its ability to destroy basal activity of NO completely, DETCA (0.1 mM)
      produced only a slight blockade of ACh-induced relaxation. However, if these
      tissues were subsequently treated with concentrations of HX (0.1 mM)/XO (16 mu ml
      1) or pyrogallol (0.1 mM), which had no effect by themselves on ACh-induced
      relaxation, a profound blockade was seen and this was reversed completely with
      SOD (250 u ml-1).8. The data suggest that basal activity of NO is more sensitive
      to inactivation by superoxide anion than ACh-stimulated activity and this
      probably results from differential protection by endogenous Cu-ZnSOD. It is
      possible therefore that endogenous SOD lowers superoxide anion levels to such an
      extent that only small amounts of NO, such as those produced under basal
      conditions, are destroyed. Following generation of superoxide anion with HX/XO or
      pyrogallol, or inhibition of Cu-Zn SOD with DETCA,levels of the free radical will
      increase such that greater amounts of NO, such as those produced following
      stimulation with ACh, will then be destroyed.

PMID- 7582535
TI  - Effects of calcitonin gene-related peptide receptor antagonists on renal actions
      of adrenomedullin.
AB  - 1. Adrenomedullin is a novel vasoactive peptide which is produced in the lungs,
      ventricle, kidneys, heart and adrenal medulla. Adrenomedullin shows homology to
      calcitonin gene-related peptide (CGRP) and has similar pharmacological actions to
      CGRP. 2. This study examined the dose-response effects of adrenomedullin (rat, 11
      50) on mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF),
      glomerular filtration rate (GFR) and renal tubular electrolyte excretion in
      Inactin-anaesthetized Sprague Dawley rats. The possible involvement of CGRP
      receptors in actions of adrenomedullin was also examined via renal arterial
      injection of a CGRP receptor antagonist, CGRP (8-37) (1 or 10 nmol kg-1) or
      [Tyr0]CGRP(28-37) (3 or 30 nmol kg-1), starting 15 min prior to the
      administration of adrenomedullin. 3. Renal arterial infusion (0.001 to 1 nmol kg
      1) of adrenomedullin did not alter MAP, HR and renal K+ excretion but dose
      dependently increased RBF and arterial conductance, GFR, urine flow and Na+
      excretion. 4. The renal actions of adrenomedullin were not blocked by either the
      low or the high dose of CGRP(8-37) or [Tyr0]CGRP(28-37). 5. The results show that
      adrenomedullin causes renal vasodilatation, increments in GFR, diuresis and
      natriuresis. The renal actions of adrenomedullin are not mediated via the
      activation of CGRP1 receptors.

PMID- 7582536
TI  - Modulation of mite antigen-induced immune responses by lecithin-bound iodine in
      peripheral blood lymphocytes from patients with bronchial asthma.
AB  - 1. Dermatophagoides farinae (Df) mite antigen induced IgE synthesis associated
      with an imbalance of cytokine production in mite-sensitive patients with
      bronchial asthma; increased production of interleukin 4 (IL-4), and decreased
      production of interferon-gamma (IFN-gamma) was specifically induced in these
      patients' lymphocytes. 2. Lecithin-bound iodine (LBI), with which children with
      bronchial asthma have been successfully treated in the range of 0.5 to 5 microM,
      concentrations comparable to LBI blood levels in medicated individuals, modified
      mite antigen-induced immune responses, thereby decreasing abnormal lymphocyte
      functions. 3. In Df antigen-driven immune responses, inhibition of IgE generation
      accompanied by suppression of IL-4 and the recovery of IFN-gamma production was
      successful when LBI was used in vitro. 4. LBI also acted on normal PBMCs by
      downregulating the IL-4-induced IgE synthesis, phytohaemagglutin (PHA)- and
      phorbol myristate acetate (PMA) plus calcium ionophore (CaI)-induced IL-4
      secretion, and by upregulating purified protein derivatives (PPD)-induced IFN
      gamma production. Therefore, LBI was capable of inhibiting the IgE and IL-4
      responses and of enhancing IFN-gamma production both from allergen-stimulated
      atopic cells and from non-atopic cells appropriately stimulated. 5. The
      expression of human histocompatibility leukocyte antigen (HLA), class II antigens
      and intercellular adhesion molecule 1 (ICAM-1) on monocytes, crucial molecules
      for T cell-monocyte interactions, was not altered by LBI. 6. LBI probably acts as
      an immunomodulator to ameliorate mite antigen-induced abnormal cell-mediated
      immune responses in patients with bronchial asthma caused by Df antigen thereby
      leading to improvement of their clinical status.

PMID- 7582537
TI  - Characterization of nitrergic neurotransmission during short- and long-term
      electrical stimulation of the rabbit anococcygeus muscle.
AB  - 1. Isolated preparations of rabbit anococcygeus muscle were exposed to electrical
      field stimulation (EFS; 50V, 0.3 ms duration, 0.08-40 Hz) for periods of 1-60 s
      (short-term EFS) or 10 min-2 h (long-term EFS). 2. Both short- and long-term EFS
      caused a contractile response which was enhanced by the nitric oxide (NO)
      synthase inhibitor, NG-nitro-L-arginine (L-NOARG), showing that it is modulated
      by endogenous NO. 3. In preparations treated with scopolamine and guanethidine
      and in which a constrictor tone was induced by histamine, both short- and long
      term EFS resulted in relaxation of the tissue. 4. Such relaxations were reversed
      by tetrodotoxin (TTX), omega-conotoxin, inhibitors of NO synthase and the NO
      scavenger, oxyhaemoglobin, indicating that they are neuronal in origin and
      nitrergic in nature. 5. The relaxations to long-term EFS persisted for the
      duration of the stimulation and were associated with sustained release of
      oxidation products of NO (NOx). The EFS-induced release of NOx was decreased by N
      iminoethyl-L-ornithine (L-NIO), an inhibitor of NO synthase, and by TTX. 6.
      Inhibitors of NO synthase, in addition, increased the basal tone of the tissue
      and reduced the basal output of NOx. The basal output of NOx was also reduced by
      TTX. 7. Long-term EFS which induces approximately 50% of the maximum relaxation
      could be enhanced by addition of L-, but not D-, arginine to the perfusion
      medium. 8. These data show that there is a continuous basal release of NO from
      nitrergic nerve terminals which maintains a relaxant tone in the rabbit
      anococcygeus muscle. 9. In addition, NO is released during short- and long-term
      EFS which further relaxes the preparation and modulates sympathetic transmission.
      Activation of the L-argimne: NO pathway for periods up to2 h does not exhaust
      nitrergic transmission in any appreciable way.

PMID- 7582538
TI  - Cholinoceptor-mediated effects on glycerol output from human adipose tissue using
      in situ microdialysis.
AB  - 1. Possible cholinoceptor-mediated effects on lipolysis were investigated in vivo
      in human subcutaneous adipose tissue of non-obese, non-smoking, healthy subjects,
      by use of microdialysis. Cholinomimetic and sympathomimetic agents were added to
      the in going dialysate solvent. 2. Addition of nicotine to the perfusion solvent
      caused a concentration-dependent reversible increase in the levels of glycerol in
      the dialysate (lipolysis index). The opposite effect (also concentration
      dependent and reversible) was caused by the addition of carbachol. The maximum
      effects were 100% stimulation and 50% inhibition, respectively, by nicotine and
      carbachol. Neither nicotine nor carbachol stimulated nutritive blood flow in
      adipose tissue (as measured with an ethanol escape technique). 3. The nicotine
      effect in situ was concentration-dependently counteracted by the nicotinic
      cholinoceptor antagonist, mecamylamine. Likewise, the carbachol effect was
      concentration-dependently counteracted by the muscarinic cholinoceptor
      antagonist, atropine. 4. When adipose tissue was pretreated with phentolamine
      plus propranolol in order to obtain a complete alpha and beta-adrenoceptor
      blockade, the subsequent addition of nicotine or carbachol still induced an
      increase and decrease in dialysate glycerol levels (lipolytic or antilipolytic
      effects), respectively. When adipose tissue was pretreated with mecamylamine or
      atropine, the subsequent addition of acetylcholine caused a reversible decrease
      and increase, respectively, of the dialysate glycerol levels. 5. Nicotine and
      carbachol had no effects on glycerol release from human isolated subcutaneous fat
      cells that were incubated in vivo. 6. In conclusion, the data demonstrate a dual
      effect of the cholinoceptor system on glycerol output inhuman adipose tissue:
      stimulation through nicotinic receptors and inhibition through muscarinic
      receptors. These effects, which are not observed in vitro, are independent of the
      adrenergic system and the local blood flow and seem not to be mediated by a
      direct action on the fat cell.

PMID- 7582539
TI  - Reduction of spike frequency adaptation and blockade of M-current in rat CA1
      pyramidal neurones by linopirdine (DuP 996), a neurotransmitter release enhancer.
AB  - 1. Linopirdine (DuP 996) has been shown to enhance depolarization-induced release
      of several neurotransmitters in the CNS through a mechanism which may involve K+
      channel blockade. The electrophysiological effects of linopirdine were therefore
      investigated directly, by use of conventional voltage recording and single
      electrode voltage-clamp. 2. Linopirdine (10 microM) reduced spike frequency
      adaptation (SFA) in rat hippocampal CA1 pyramidal neurones in vitro. The
      reduction of SFA comprised an increase in number of spikes and a reduction in
      inter-spike intervals after the first, but with no effect on time to first spike.
      Linopirdine also caused a voltage-dependent depolarization of resting membrane
      potential (RMP). 3. M-current (IM), a current known to underlie SFA and to set
      RMP, was blocked by linopirdine in a reversible, concentration-dependent manner
      (IC50 = 8.5 microM). This block was not reversed by atropine (10 microM). 4.
      Linopirdine did not affect IQ, the slow after-hyperpolarization following a spike
      train, or spike duration. 5. Linopirdine may represent a novel class of K+
      blocker with relative selectivity for the M-current. This block of IM is
      consistent with the suggestion from a previous study that linopirdine may affect
      a tetraethylammonium-sensitive channel, and it could be speculated that IM
      blockade may be involved with the enhancement of neurotransmitter release by
      linopirdine.

PMID- 7582540
TI  - NMDA-induced glutamate and aspartate release from rat cortical pyramidal
      neurones: evidence for modulation by a 5-HT1A antagonist.
AB  - 1. We have investigated an aspect of the regulation of cortical pyramidal neurone
      activity. Microdialysis was used to assess whether topical application of drugs
      (in 10 microliter) to fill a burr hole over the frontal cortex, where part of the
      corticostriatal pathway originates, would change concentrations of the excitatory
      amino acids glutamate and aspartate in the striatum of the anaesthetized rat. 2.
      Topical application of N-methyl-D-aspartate (NMDA, 2 and 20 mM) dose-dependently
      increased glutamate and aspartate concentrations in the striatum. Coapplication
      of tetrodotoxin (10 microM) blocked the NMDA-evoked rise in these amino acids. A
      calcium-free medium, perfused through the probe also blocked the rise, indicating
      that it was due to an exocytotic mechanism in the striatum. 3. It was
      hypothesized that the rise observed was due to an increase in the activity of the
      corticostriatal pathway. As 5-hydroxytryptamine1A (5-HT1A) receptors are enriched
      on cell bodies of corticostriatal neurones, a selective 5-HT1A-antagonist (WAY
      100135) was coapplied with the lower dose of NMDA. Compared to NMDA alone,
      coapplication of 50 microM WAY 100135 significantly increased glutamate release.
      This effect was sensitive to tetrodotoxin and calcium-dependent. Application of
      50 microM WAY 100135 alone significantly enhanced glutamate release above
      baseline; this was also tested at 100 microM (not significant). 4. Compared to
      NMDA alone, coapplication of WAY 100135 (20 microM) significantly enhanced
      aspartate release; the mean value was also increased (not significantly) with 50
      microM. This rise was calcium-dependent, but not tetrodotoxin-sensitive. WAY
      100135 (100 microM) reduced NMDA-induced aspartate release. WAY 100135 (100
      microM) reduced NMDA-induced aspartate release. Application of the drug alone had
      no effect on basal aspartate release.5. Coapplication of the 5-HT1A agonist, 8
      OHDPAT (5 sanM) with NMDA did not affect the NMDA evoked increase in glutamate
      and aspartate.6. Topical application of high potassium (100 sanM) to the surface
      of the cortex did not result in a detectable rise in striatal glutamate or
      aspartate.7. Perfusion of WAY 100135 (tested at 50 microM) through the dialysis
      probe did not affect glutamate oraspartate concentrations.8. It was concluded
      that a selective 5-HT1A-antagonist can increase the activity of corticostriatal
      pyramidal neurones. As in Alzheimer's disease hypoactivity of pyramidal neurones
      almost certainly exists, a selective 5-HT1A-antagonist may be potentially useful
      in the treatment of the cognitive symptoms of this disease.

PMID- 7582541
TI  - Inhibition by N-acetyl-5-hydroxytryptamine of nitric oxide synthase expression in
      cultured cells and in the anaesthetized rat.
AB  - 1. Induction of the calcium-independent isoform of nitric oxide (NO) synthase
      (iNOS) in various cell types has been implicated in the circulatory failure in
      experimental models of septic shock. Tetrahydrobiopterin (BH4) appears to be an
      essential co-factor for NO formation and therefore an inhibition of its
      biosynthesis represents a feasible therapeutic target. We have investigated the
      effects of an inhibitor of BH4 synthesis, N-acetyl-5-hydroxytryptamine (N
      acetylserotonin, NAS), on the expression of iNOS in cultured macrophages and
      smooth muscle cells in vitro, and on the hypotensive response to bacterial
      lipopolysaccharide (LPS) in the anaesthetized rat in vivo. 2. NAS (0.01-5 mM)
      caused a concentration-dependent inhibition of the accumulation of nitrite in the
      conditioned medium of LPS/interferon-gamma (IFN gamma)-stimulated RAW 264.7
      macrophages and interleukin-1 beta (IL-1 beta)-activated vascular smooth muscle
      cells (VSMC). This effect was paralleled by a similar decrease in the iNOS
      protein content of these cells, as determined by immunoblot analysis. 3.
      Pretreatment of RAW 264.7 macrophages with the BH4 precursor, dihydrobiopterin
      (BH2, 0.1 mM) did not restore nitrite formation in the presence of NAS (1 mM). 4.
      Intravenous administration of NAS (1 mg kg-1 min-1 for 30 min) in anaesthetized
      rats significantly reduced the fall in mean arterial blood pressure, restored the
      pressor response to noradrenaline (1 micrograms kg-1), and ameliorated the
      increase in plasma nitrite following exposure to LPS (10 mg kg-1). 5. NAS
      pretreatment also attenuated iNOS activity in lung homogenates, as determined by
      the conversion of radiolabelled L-arginine to L-citrulline, and partially
      restored the constrictor effect of noradrenaline in aortic rings isolated from
      LPS-treated rats. Moreover, NAS significantly reduced the rise in the plasma
      concentration of tumour necrosis factor alpha (TNFalpha) in response to LPS.6.
      These findings suggest that NAS inhibits the expression rather than the activity
      of iNOS in cultured macrophages and smooth muscle cells. This effect of NAS
      appears to be independent of the availability of BH4, but may be related to an
      attenuation of the release of TNFalpha following LPS administration, as shown in
      the anaesthetized rat. This mechanism may also account for the beneficial
      haemodynamic effect of NAS in our experimental model of endotoxaemia.

PMID- 7582542
TI  - Effects of metformin treatment on glucose transporter proteins in subcellular
      fractions of skeletal muscle in (fa/fa) Zucker rats.
AB  - 1. The present study was designed to clarify the cellular mechanism through which
      the antihyperglycaemic drug, metformin, exerts its effects. For this purpose the
      contents of glucose transporter protein isoforms GLUT1 and GLUT4 were measured in
      plasma membrane and intracellular membrane fractions of skeletal muscle obtained
      from genetically obese, insulin-resistant Zucker rats. 2. Hindlimb muscles were
      dissected from metformin-treated (300 mg kg-1 day-1, p.o., for 12 days) and
      control rats in basal treatment state, and after acute stimulation with insulin
      (22 u kg-1, i.p.). Since metformin treatment reduces food intake, we also used a
      pair-fed control group to investigate the effects of altered insulinaemia per se.
      Glucose transporter levels were analysed by Western blot and slot blot
      techniques. In addition, 2-deoxy-[14C]-glucose uptake in isolated muscle strips
      was evaluated. 3. No changes were noted in the contents of GLUT1 proteins in any
      of the subcellular fractions after metformin treatment. The contents of GLUT4 in
      subcellular fractions were not altered in the basal treatment state. After acute
      insulin exposure the content of GLUT4 in the intracellular membrane fraction
      declined significantly in the metformin-treated group, while no significant
      effect was seen in the plasma membrane fraction. In agreement with these results,
      metformin treatment did not alter 2-deoxyglucose uptake into isolated muscle
      strips. 4. In conclusion, the present study does not support the concept that
      metformin would enhance translocation of glucose transporter proteins from the
      intracellular compartment to the plasma membrane in skeletal muscle in vivo.

PMID- 7582543
TI  - Mechanism of angiogenic effects of saponin from ginseng Radix rubra in human
      umbilical vein endothelial cells.
AB  - 1. The effects of saponin from Ginseng Radix rubra on angiogenesis (tube
      formation) and its key steps (protease secretion, proliferation and migration) in
      human umbilical vein endothelial cells (HUVEC) were examined to elucidate the
      mechanism of the tissue repairing effects of Ginseng Radix rubra. The effect on a
      wound healing model was also studied. 2. Tube formation was measured by an in
      vitro system. The activity and immunoreactivity of tissue-type plasminogen
      activator (tPA) as a protease for angiogenesis and the immunoreactivity of its
      inhibitor, plasminogen activator inhibitor-1 (PAI-1), were measured in
      conditioned medium of HUVEC stimulated for 24 h with saponin. Cell proliferation
      was measured by counting the cell numbers at 2-7 days after seeding. Migration
      was measured by Boyden's chamber method. The effect on wound healing was studied
      in the skin of diabetic rats. 3. Saponin at 10-100 micrograms ml-1 significantly
      stimulated tube formation by HUVEC in a dose-dependent manner. Saponin in a
      similar concentration-range increased the secretion of tPA from HUVEC as
      estimated by immunoreactivity and enzyme activity. On the other hand, PAI-1
      immunoreactivity was slightly increased at 10 micrograms ml-1 of saponin, but
      then was significantly decreased at 50 and 100 micrograms ml-1. Cell
      proliferation was only slightly enhanced by 1-100 micrograms ml-1 of saponin, but
      migration was significantly enhanced by 10-100 micrograms ml-1 in a dose
      dependent manner. Moreover, saponin stimulated wound healing with enhanced
      angiogenesis in vivo. 4. These results indicate that saponin stimulates tube
      formation mainly by modifying the balance of protease/protease inhibitor
      secretion from HUVEC and enhancing the migration of HUVEC, and that it is
      effective in vivo.

PMID- 7582544
TI  - Endogenous nitric oxide modulation of potassium-induced changes in guinea-pig
      airway tone.
AB  - 1. An experimental set up is used whereby the serosal (out)side or mucosal
      (in)side of the guinea-pig isolated tracheal tube can be stimulated selectively
      with drugs and reactivity measured. 2. Potassium induces a concentration
      dependent (5-70 mM) monophasic contraction of tracheal tubes when added on the
      outside. In contrast, on the inside, potassium induces a concentration-dependent
      relaxation at low concentrations (5-40 mM) which was reversed into a contraction
      up to approximately basal tone at higher concentrations (50-70 mM). 3. Epithelium
      denudation reversed the potassium-induced relaxation into a contraction.
      Interestingly, in the 'half' epithelium-denuded trachea the contractions were
      significantly (P < 0.01) reduced by 46% compared to complete epithelium-denuded
      tissues. 4. Incubation with the nitric oxide (NO) synthase inhibitor N omega
      nitro-L-arginine methyl ester (L-NAME, 120 microM) for 30 min on the inside of
      the tracheal tube completely prevented the relaxation. However, L-NAME did not
      reverse the potassium-induced relaxation into a contraction. This indicates that
      potassium does not penetrate through the epithelial layer. 5. It is concluded
      that depolarization of smooth muscle cells leads to a monophasic contraction and
      that depolarization of the epithelium leads to a relaxation of tracheal smooth
      muscle. The epithelial layer has an important barrier function and can release
      relaxing factors like NO.

PMID- 7582545
TI  - ATP, a partial agonist of atypical P2Y purinoceptors in rat brain microvascular
      endothelial cells.
AB  - 1. Purinoceptor responses were analyzed in B10 cells, a clonal population of rat
      brain capillary endothelial cells. 2. B10 cells lack P2U receptors as evidenced
      by the lack of UTP responses and the failure to amplify P2U-related sequences by
      polymerase chain reaction. 3. B10 cells responded to adenine nucleotides by large
      increases in [Ca2+]i. Half maximum effective concentrations were 2-methylthio
      ATP: 180 nM > 2-chloro-ATP: 310 nM = ADP: 330 nM > adenosine 5'-O-(3
      thiotrisphosphate): 2.3 microM = ATP: 2.7 microM. The maximum response to ATP was
      only 55% of that to ADP while that to ATP derivatives was 75%. 4. The actions of
      adenine nucleotides were not associated with a measurable activation of
      phospholipase C. 5. Cross desensitizations of the actions of ADP and ATP were
      observed. 6. In additivity experiments, ADP superposed its action on top of that
      of ATP and ATP partially inhibited the action of ADP. 7. It is concluded that ATP
      acts as a partial agonist of the P2Y-like receptor of brain capillary endothelial
      cells.

PMID- 7582547
TI  - Increased sensitivity of rat myometrium to the contractile effect of platelet
      activating factor before delivery.
AB  - 1. The contractile effects of platelet activating factor (PAF) were compared in
      the myometrium isolated from non-pregnant and pregnant rats. 2. In the non
      pregnant myometrium, PAF, at a concentration of 0.1 microM, did not change muscle
      tension and induced only a small transient contraction at 10 microM. 3. The
      contractile responses to PAF increased with the progress of gestation. In the
      late pregnant myometrium (21 day after gestation), PAF (0.1 nM-10 microM) induced
      large and relatively sustained contractions. The threshold concentration of PAF
      was decreased by approximately 10,000 times and the maximum contraction was
      increased 5 times by day 21 of gestation. 4. PAF (10 microM) increased the
      cytosolic Ca2+ concentration ([Ca2+]i) and muscle contraction to levels higher
      than those induced by high K+ in the pregnant rat myometrium (day 21). Verapamil
      (10 microM), a voltage-dependent Ca2+ channel blocker, decreased the stimulated
      [Ca2+]i and muscle tension to 49.6% and 22.7%, respectively, while the same
      concentration of verapamil completely inhibited the high K(+)-induced responses.
      5. PAF (10 microM) induced a transient increase in [Ca2+]i with no contraction in
      the absence of external Ca2+ in the pregnant myometrium (day 21). 6. These
      results suggest that PAF induces contraction in rat myometrium by increasing Ca2+
      influx. Although PAF released Ca2+ from stored sites, this Ca2+ does not seem to
      contribute to the PAF-induced contraction. Our major finding is that the
      sensitivity of the myometrium to PAF increased after gestation and that this may
      play a role in delivery.

PMID- 7582546
TI  - Ca2+ increase and Ca(2+)-influx in human tracheal smooth muscle cells: role of
      Ca2+ pools controlled by sarco-endoplasmic reticulum Ca(2+)-ATPase 2 isoform.
AB  - 1. The contribution of sarco-endoplasmic reticulum Ca(2+)-ATPases (SERCA)
      regulated Ca2+ stores to the increase in intracellular free calcium ([Ca2+]i)
      induced by bradykinin (BK) was investigated in fura-2 loaded human tracheal
      smooth muscle cells (TSMC). For this purpose, we used thapsigargin, a selective
      inhibitor of Ca(2+)-ATPases of intracellular organelles. 2. Thapsigargin (10(-9)
      to 10(-6) M) induced a dose-dependent increase in [Ca2+]i in the presence of
      external Ca2+ with an EC50 value of 7.33 +/- 1.26 nM. In Ca(2+)-free conditions,
      the addition of Ca2+ (1.25 mM) caused an increase in [Ca2+]i which was directly
      proportional to the pre-incubation time of the cells with thapsigargin. Net
      increases of 60 +/- 9, 150 +/- 22 and 210 +/- 27 nM were obtained after 1, 3 and
      5 min, respectively. 3. In the presence of extracellular Ca2+, BK induced a
      typical biphasic increase in [Ca2+]i with a fast transient phase and a sustained
      phase. The sustained component was reversed by addition of a bradykinin B2
      receptor antagonist (Hoe 140, 10(-6) M) to the buffer as well as by deprivation
      of Ca2+. The transient phase induced by BK, histamine and carbachol was inhibited
      in a time-dependent way by preincubation of the cells with thapsigargin. 4.
      Comparative western blotting of human TSMC membranes using anti-SERCA2 isoform
      specific antibodies clearly showed the greater expression of the 100-kDa SERCA2-b
      isoform compared with the SERCA2-a isoform. 5. Our data show that thapsigargin
      sensitive Ca2+ stores contribute significantly to the activation of human TSMC
      which suggests a role for these stores in the subsequent induction of Ca2+
      influx. These stores appear to be controlled by the Ca2+-ATPases (SERCA2-b
      isoform) which could also participate in the regulation of Ca2+ influx through
      the plasma membrane.

PMID- 7582548
TI  - Endothelium-dependent contraction in intrapulmonary arteries: mediation by
      endothelial NK1 receptors and TXA2.
AB  - 1. We have examined whether three natural tachykinins, substance P (SP),
      neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent
      contraction (EDC) in the rabbit isolated intrapulmonary artery. 2. Removal of the
      endothelium almost abolished the contraction induced by SP (10(-8) M) while it
      did not attenuate the contraction induced by SP (10(-7) M), NKA (10(-9) - 10(-7)
      M) or NKB (10(-8) and 10(-7) M). 3. The EDC induced by SP (10(-8) M) was
      abolished by NK1 antagonists (FK-888, CP-96345, CP-99994 and SR-140333) but not
      by an NK2 antagonist (SR-48968). 4. The EDC induced by SP was attenuated by cyclo
      oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase
      inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5. The
      rank order of potency causing endothelium-independent contraction (EIC) was NKA >
      NKB > SP. The EIC induced by SP (10(-7) M) was attenuated by an NK2 antagonist
      but not by NK1 antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase
      inhibitors or a TXA2 antagonist. 6. In conclusion, SP at 10(-8) M induces EDC via
      endothelial NK1 receptors and TXA2 production, and SP at 10(-7) M induces EIC via
      NK2 receptors in the rabbit intrapulmonary artery.

PMID- 7582551
TI  - Influence of graded changes in vasomotor tone on the carotid arterial mechanics
      in live spontaneously hypertensive rats.
AB  - 1. The contribution of vasomotor tone to the increased stiffness of carotid
      arteries in living spontaneously hypertensive rats (SHR) is largely unknown.
      Whether a reduced vascular tone is associated with an increase or a decrease in
      arterial stiffness in vivo remains to be determined. The goal of the present
      investigation was to show that a decrease in vascular tone is associated with a
      decrease in arterial stiffness, independent of the structural composition of the
      arterial wall. 2. New high resolution echo-tracking techniques were used to
      evaluate pulsatile changes of carotid blood pressure and diameter following
      transient and graded changes of vasomotor tone produced by the dihydropyridine
      derivative, isradipine. Treatment for 8 weeks was given to groups of SHR rats
      either with a low (0.6 kg day-1) or a high (2.6 mg kg-1 day-1) dose. Another SHR
      group received an acute dose of 2.6 mg kg-1 day-1. Results were compared to those
      of placebo-treated Wystar-Kyoto (WKY) and SHR rats. Whatever the dosage, acute or
      chronic calcium blockade caused a decrease in blood pressure which was maximal 1
      h after administration and disappeared after the 16th h. Carotid arterial
      thickness and the composition of the arterial wall was determined from
      histomorphometry. 3. In placebo-treated SHR, the inverse relationship relating
      blood pressure to carotid arterial distensibility was significantly shifted
      toward higher values of blood pressure compared to the curve of normotensive
      placebo-treated WKY rats. The curve of SHR receiving chronically a non
      antihypertensive (0.6 mg kg-1 day-1) isradipine dose prolonged that of placebo
      treated SHR toward lower values of blood pressure, so that carotid distensibility
      was significantly higher than in WKY for the same diameter and blood pressure
      level (145 mmHg). With administration of a chronic antihypertensive dose (2.6 mg
      kg-1 day-1) causing a significant decrease in arterial function. Acute
      antihypertensive calcium blockade with a single isradipine dose (2.6 mg kg-1 day
      1) caused a similar shift in the pressure-distensibility curve toward the WKY
      curve although the histomorphometric composition of the arterial wall differed
      significantly from that of chronically treated animals. 4. The study provides
      evidence that, in living SHR submitted to calcium blockade, (i) a low dose of
      isradipine causing no substantial antihypertensive effect is associated with a
      significant elevation of carotid arterial distensibility for the same pressure
      and diameter as normotensive controls, and (ii) an acute or chronic dose causing
      a substantial antihypertensive effect is associated with a transient shift of the
      SHR distensibility-pressure curve toward a physiological arterial function,
      increasing carotid distensibility for the same pressure and diameter as WKY
      controls. Since such findings were observed independently of the
      histomorphometric composition of the arterial wall, they imply that the transient
      decrease in arterial stiffness produced by calcium blockade should involve
      specific changes in the connections between arterial smooth muscle and
      extracellular matrix.

PMID- 7582549
TI  - Endothelium-dependent relaxation to acetylcholine in bovine oviductal arteries:
      mediation by nitric oxide and changes in apamin-sensitive K+ conductance.
AB  - 1. Mechanisms underlying the relaxant response to acetylcholine (ACh) were
      examined in bovine oviductal arteries (o.d. 300-500 microns and i.d. 150-300
      microns) in vitro. Vascular rings were treated with indomethacin (10 microM) to
      prevent the effects of prostaglandins. 2. ACh elicited a concentration-related
      relaxation in ring segments precontracted with noradrenaline (NA), which was
      abolished by endothelium denudation. 3. The ACh-induced relaxation was attenuated
      but not abolished by NG-nitro-L-arginine (L-NOARG, 1 microM-1 mM), an inhibitor
      of nitric oxide (NO) formation. The inhibition caused by L-NOARG (10 microM) was
      reversed by addition of excess of L-arginine but not D-arginine (1 mM). 4. In
      high K+ (40-60 mM)-contracted rings, ACh was a much less effective vasodilator
      and its relaxant response was completely abolished by L-NOARG (100 microM). 5. In
      NA (10 microM)-contracted rings, ACh induced sustained and concentration
      dependent increases in cyclic GMP, which were reduced below basal values by L
      NOARG (100 microM), while potent relaxation persisted. Similar increases in
      cyclic GMP were evoked by ACh in high K+ (50 mM)-treated arteries and under these
      conditions, both cyclic GMP accumulation and relaxation were L-NOARG-sensitive.
      6. S-nitroso-L-cysteine (NC), a proposed endogenous precursor of endothelial NO,
      also induced cyclic GMP accumulation in NA-contracted oviductal arteries. 7.
      Methylene blue (MB, 10 microM), a proposed inhibitor of soluble guanylate
      cyclase, inhibited both endothelium-dependent relaxation to ACh and endothelium
      independent response to exogenous NO, whereas relaxation to NC remained
      unaffected. 8. The L-NOARG-resistant response to ACh was not affected by either
      ouabain (0.5 mM), glibenclamide (3 microM), tetraethylammonium (TEA, 1 mM) or
      charybdotoxin (50 nM), but was selectively blocked by apamin (0.1-1 microM).
      However, apamin did not inhibit either relaxation to ACh in high K(+)-contracted
      rings or endothelium-independent relaxation to either NO or NC. 9. Apamin and MB
      inhibited ACh-induced relaxation in an additive fashion, suggesting the
      involvement of two separate modulating mechanisms. 10. These results suggest that
      ACh relaxes bovine oviductal arteries by the release of two distinct endothelial
      factors: a NO-like substance derived from L-arginine, which induces cyclic GMP
      accumulation in smooth muscle, and another non-prostanoid factor acting by
      hyperpolarization mechanisms through alterations in apamin-sensitive K+
      conductance.

PMID- 7582553
TI  - Modelling of the pharmacodynamic interaction of an A1 adenosine receptor agonist
      and antagonist in vivo: N6-cyclopentyladenosine and 8-cyclopentyltheophylline.
AB  - 1. The purpose of this investigation was to develop a pharmacokinetic
      pharmacodynamic model for the interaction between an adenosine A1 receptor
      agonist and antagonist in vivo. The adenosine A1 receptor agonist, N6
      cyclopentyladenosine (CPA) and the antagonist, 8-cyclopentyltheophylline (CPT)
      were used as model drugs. The CPA-induced reduction in mean arterial pressure and
      heart rate were used as measurements of effect. 2. Four groups of eight rats each
      received 200 micrograms kg-1 of CPA i.v. in 5 min during a steady-state infusion
      of CPT at a rate of 0, 57, 114 or 228 micrograms kg-1 h-1. The haemodynamic
      parameters were continuously measured and frequent blood samples were taken to
      determine the pharmacokinetics of the drugs. 3. CPT had no influence on the
      pharmacokinetics of CPA and the baseline values of the haemodynamic variables.
      Furthermore, no clear antagonism by CPT was observed of the CPA-induced reduction
      in mean arterial pressure. However, CPT antagonized the effect on heart rate, and
      with increasing CPT concentrations, a parallel shift of the CPA concentration
      effect relationship to the right was observed. 4. An agonist-antagonist
      interaction model was used to characterize the interaction quantitatively. On the
      basis of this model, the pharmacodynamic parameters of both CPA and CPT could be
      estimated. For CPA the values were (mean +/- s.e.): Emax = 198 +/- 11 b.p.m.,
      EC50 = 2.1 +/- 0.7 ng ml-1, Hill factor = 2.3 +/- 0.6 and for CPT: EC50 = 3.7 +/-
      0.3 ng ml-1 and Hill factor = 3.1 +/- 0.1. 5. It is concluded that the
      competitive agonist-antagonist interaction model may be of value to characterize
      quantitatively the pharmacodynamic interactions between adenosine A1 receptor
      ligands in vivo.

PMID- 7582554
TI  - Monohydroxyethylrutoside as protector against chronic doxorubicin-induced
      cardiotoxicity.
AB  - 1. The clinical use of the antitumour agent, doxorubicin, is largely limited by
      the development of a cumulative dose-related cardiotoxicity. This toxicity is
      generally believed to be caused by the formation of oxygen free radicals. In
      earlier studies it was established that flavonoids, naturally occurring
      antioxidants, can provide some degree of protection. In this study we
      investigated whether 7-monohydroxyethylrutoside (monoHER), a powerful
      antioxidative flavonoid with extremely low toxicity, can provide protection to an
      extent comparable to the clinically successful Cardioxane (ICRF-187). 2. Balb/c
      mice of 20-25 g were equipped i.p. with a telemeter to measure ECG. They were
      given 6 i.v. doses of doxorubicin (4 mg kg-1) at weekly intervals. ICRF-187 (50
      mg kg-1) or monoHER (500 mg kg-1) were administered i.p. 1 h before doxorubicin
      administration. In the 2 monoHER groups the treatment continued with either 1 or
      4 additional injections per week. A saline and monoHER treated group served as
      controls. After these 6 weeks, they were observed for another 2 weeks. 3. At the
      end of this study (week 8) the ST interval had increased by 16.7 +/- 2.7 ms (mean
      +/- s.e. mean) in doxorubicin-treated mice. At that time, the ST interval had
      increased by only 1.8 +/- 0.9 ms in ICRF-187 co-mediated mice and in monoHER co
      medicated mice by only 1.7 +/- 0.8 and 5.1 +/- 1.7 ms (5- and 2-day schedule,
      respectively, all P < 0.001 relative to doxorubicin and not significantly
      different from control). The ECG of the control animals did not change during the
      entire study. The QRS complex did not change in either group.4. It can be
      concluded that monoHER protects against doxorubicin-induced cardiotoxicity and
      merits further evaluation in this respect.

PMID- 7582552
TI  - Characteristics of nucleotide receptors that cause elevation of cytoplasmic
      calcium in immortalized rat brain endothelial cells (RBE4) and in primary
      cultures.
AB  - 1. A dual-wavelength microfluorimetric method using Fura-2 as calcium indicator
      was applied to cells from an immortalized cell line of rat brain microvascular
      endothelial cells (RBE4), and to primary cultured rat brain endothelial cells. 2.
      In RBE4 cells, a brief (20 s) pulse of extracellular ATP (100 microM) induced a
      transient increase in the cytoplasmic calcium level ([Ca2+]i). Control responses
      to 100 microM ATP consisted of a ratio increase of 0.64 +/- 0.03 (mean +/- s.e.,
      n = 51). Responses were seen at a concentration of 2.5 microM and were maximal at
      100-1000 microM. When extracellular calcium was chelated with EGTA, the transient
      increase in [Ca2+]i was not affected. The results are consistent with Ca2+
      mobilization from intracellular stores. 3. The purinoceptor involved belongs to
      the P2 subtype, since the agonist potency order among the adenine nucleotides was
      ATP > ADP > AMP. Moreover, the increase in [Ca2+]i evoked by ATP was partially
      inhibited by the P2 antagonist, suramin but was not affected by 8
      phenyltheophylline, a P1-purinoceptor antagonist. The strong desensitization
      observed with repeated applications of ATP is also typical of a P2 receptor. 4. 2
      Methylthio-ATP (2meS-ATP 100 microM), a P2Y agonist, elevated [Ca2+]i in only 17%
      of the cells tested; however, 2meS-ATP was found to antagonize the effect of ATP
      in all cells tested. The increase in [Ca2+]i evoked by ATP was inhibited by 500 s
      application of the P2Y purinoceptor antagonist, Reactive Blue 2 at 10 microM,
      while 60 s application of 100 microM was ineffective. 5. The uracil nucleotide,
      UTP (100 microM) was as effective as ATP in increasing [Ca2+]i. The effects of
      ATP and UTP were not additive. Cells desensitized to the action of ATP (or UTP)
      were unable to respond to UTP (or ATP).6. alpha,beta Methylene-ATP (alpha,beta
      meATP 100 microM), a P2x, agonist, elevated [Ca2+], in only 40% of the cells
      tested. In these cells it was less effective than ATP in increasing [Ca2+]i.7.
      Cells desensitized to the action of ADP responded, to a smaller extent, to ATP.
      In contrast, cells desensitized to the action of ATP were unable to respond to
      ADP.8. On primary cultures of brain endothelial cells the increase in [Ca2+]i in
      response to extracellular ATP(100 microM) and UTP (100 microM) was of an
      equivalent amplitude, and similar to the response in RBE4 cells.The pattern of
      desensitization was also similar to that in RBE4 cells.9 This comparative study
      indicates that in well-characterized brain microvascular endothelial cells that
      retain brain endothelial characteristics, the major class of nucleotide receptor
      is of the P2mu type. The implications for physiology are discussed.

PMID- 7582550
TI  - An EP receptor with a novel pharmacological profile in the T-cell line Jurkat.
AB  - 1. Comparison of the rank order of potency of the natural prostanoids
      prostaglandin E2 (PGE2), PGD2, PGF2 alpha and carbaprostacyclin in stimulating
      cyclic AMP in Jurkat cells is consistent with the presence of an EP receptor. 2.
      Lack of responsiveness to the EP1/EP3 selective agonist, sulprostone, and the EP2
      agonists, butaprost and AH 13205, indicates that this receptor is not of the EP1,
      EP2 or EP3 subtypes. 3. Inhibition of PGE2-stimulated cyclic AMP by the EP4
      antagonist, AH 23848 is non-competitive, unlike the competitive antagonism
      reported in the pig saphenous vein EP4 preparation. Furthermore, 16,16-dimethyl
      PGE2 is 100 fold less potent than PGE2 in Jurkat cells, while these agonists are
      equipotent in the rabbit jugular vein purported EP4 preparation. In addition, 1
      OH PGE1, which also is active in the rabbit jugular vein preparation, is inactive
      in Jurkat cells at concentrations up to 1 x 10(-4) M. These data are not wholly
      consistent with any adenylate cyclase coupled EP receptor described to date. 4.
      It is postulated that an EP receptor, positively coupled to adenylate cyclase,
      with a unique pharmacological profile is present in Jurkat cells.

PMID- 7582556
TI  - Effect of P2-purinoceptor antagonists on glutamatergic transmission in the rat
      hippocampus.
AB  - 1. A study has been made of the effects of P2-purinoceptor antagonists on the
      evoked excitatory postsynaptic currents (e.p.s.cs) generated in CA1 pyramidal
      cells on stimulation of Schaffer collaterals and in CA3 pyramidal cells on
      stimulation of mossy fibres. The effects of these antagonists on currents
      generated in the cells on application of glutamate has also been determined. 2.
      Suramin blocked the evoked e.p.s.cs with an 50% inhibition (ID50) of 62 +/- 8
      microM (mean +/- s.e.mean, n = 17), spontaneous miniature e.p.s.cs and the
      currents induced by application of 100 microM glutamate with an ID50 = 121 +/- 36
      microM (n = 15) in all the cells studied. 3. Reactive Blue 2 (RB-2) in a
      concentration of 200 microM decreased the e.p.s.cs by 80 +/- 10% (n = 6) and the
      glutamate-activated currents by 83 +/- 3% (n = 6). 4. Pyridoxal-phosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS) in the concentration-range of 40-500
      microM decreased the amplitude of the e.p.s.cs in 12 out of 13 cells studied.
      PPADS at 200 microM reduced the amplitude of the e.p.s.cs by 60 +/- 10% (n = 3).
      PPADS did not affect the glutamate-induced currents in 4 cells and produced
      potentiation of the current amplitude by 60 +/- 10% in 4 other cells. 5. These
      results suggest that both presynaptic and postsynaptic P2-purinoceptors in the
      hippocampus can modulate the release and action of endogenous glutamate.

PMID- 7582558
TI  - Calcitonin gene-related peptide (CGRP)-enhanced non-adrenergic non-cholinergic
      contraction of guinea-pig proximal colon.
AB  - 1. We have investigated the effect of calcitonin gene-related peptide (CGRP) on
      non-adrenergic, non-cholinergic (NANC) excitatory transmission to the
      longitudinal muscle of the guinea-pig proximal colon. 2. In the presence of
      atropine (0.3 microM), guanethidine (5 microM), hexamethonium (100 microM) and
      indomethacin (3 microM), electrical field stimulation (EFS, 1 Hz, 0.3 ms for 10
      s) produced tetrodotoxin-(300 nM)-sensitive contractions which were reduced by
      the combined administration of FK 888 (10 microM) and MEN 10,376 (0.3 microM), to
      block tachykinin NK1 and NK2 receptors, respectively. Thus, the EFS-induced NANC
      contractions are a tachykinin-mediated response. 3. CGRP, at concentrations
      higher than 0.1 nM, caused an increase in the electrically-evoked, NANC
      contractions in a concentration-dependent manner and at 10 nM produced a maximal
      effect (pEC50 = 9.20 +/- 0.17, n = 6). 4. 5-Hydroxytryptamine (5-HT, 1-100 nM)
      also caused an increase in the EFS-induced NANC contractions in a concentration
      dependent manner and at 30 nM produced a maximal effect (pEC50 = 8.06 +/- 0.09, n
      = 4), but calcitonin (10-100 nM) failed to enhance the EFS-induced NANC
      responses. Moreover, a 5-HT4 receptor antagonist, DAU 6285 (3 microM) abolished
      the enhancing action of 5-HT (30 nM). 5. The combined administration of FK 888
      (10 microM) plus MEN 10,376 (0.3 microM) abolished the enhancement of EFS-induced
      NANC contractions by CGRP (10 nM), but DAU 6285 (3 microM) had no effect on the
      enhancement. 6. Human CGRP8-37 (1 microM), a CGRP1 receptor antagonist had no
      effect on the submaximal enhancement of the electrically-evoked, NANC
      contractions by CGRP (1 nM).7. CGRP (30 nM) had no effect on contractions evoked
      by exogenous substance P (0.3-1 nM).8. These results indicate that in the guinea
      pig proximal colon, CGRP produced an enhancement ofNANC contraction induced by
      EFS through prejunctional mechanisms and that the enhancement is mediated by the
      stimulation of non-CGRP1 receptors located on intramural tachykininergic
      neurones.Further, the possible contribution of 5-HT to the enhancing effect of
      CGRP appeared to be negligible.

PMID- 7582559
TI  - Characterization of arginine vasopressin actions in human uterine artery: lack of
      role of the vascular endothelium.
AB  - 1. The effect of arginine vasopressin (AVP) on human uterine artery rings, both
      intact and denuded of endothelium, was investigated. 2. Initially, AVP (63 pM-32
      nM) induced concentration-dependent contraction of human uterine artery (pD2 =
      8.92 +/- 0.01). Removal of the endothelium did not affect the concentration
      response curve for AVP (pD2 = 8.83 +/- 0.03). 3. In contrast, human uterine
      arteries, both intact and denuded of endothelium, did not respond to the addition
      of 1-desamino-8-D-arginine vasopressin (dDAVP, 1 nM-1 microM). 4. In both types
      of preparations, [d(CH2)5Tyr(Me)AVP (1-10 nM) and [d(CH2)5,D-Ile2,Ile4]AVP (300
      nM-3 microM) produced parallel rightward shifts of the curves for AVP. The Schild
      plots constrained to a slope of unity gave the following -log KB values:
      [d(CH2)5Tyr(Me)]AVP vs. [d(CH2)5,D-Ile2,Ile4]AVP 9.66 vs. 6.69 and 9.61 vs. 6.80
      for human uterine artery, intact and denuded of endothelium, respectively. 5. The
      pKA values for AVP itself also did not differ between preparations: 6.56 and 6.43
      for human uterine artery with and without endothelium, respectively. In both
      types of preparations, the receptor reserve (KA/EC50) was considerably greater
      than unity (intact vs. denuded: 228 vs. 244). 6. It is concluded that, in human
      uterine artery, AVP induces contractions that are not modulated by the
      endothelium. It is likely that AVP acts as a full agonist on human uterine
      artery, regardless of the endothelial condition. On the basis of differential
      antagonists affinity and affinity of AVP itself, it is probable that vasopressin
      receptors involved in AVP-induced contraction in human uterine arteries belong to
      the V1a or V1a-like subtype.

PMID- 7582557
TI  - The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4
      methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the
      CYP2D6 poor metabolizer phenotype.
AB  - 1. The effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or
      'Ecstasy') and its N-demethylated product, 3,4-methylenedioxyamphetamine (MDA) on
      both rectal temperature and long term neurotoxic loss of cerebral 5
      hydroxytryptamine (5-HT) has been studied in male and female Dark Agouti (DA)
      rats. The female metabolizes debrisoquine more slowly than the male and its use
      has been suggested as a model of the human debrisoquine 4-hydroxylase poor
      metabolizer phenotype. 2. A novel h.p.l.c. method was developed and used to
      measure plasma MDMA and MDA concentrations in the DA rats. 3. The hyperthermic
      response following MDMA was enhanced in female rats. Plasma MDMA concentrations
      were also 57% higher than in males 45 min post-injection, while plasma
      concentrations of MDA were 48% lower. 4. Plasma concentrations of MDMA and MDA in
      male rats were unaffected by pretreatment with proadifen (15 mg kg-1) or
      quinidine (60 mg kg-1), but the hyperthermic response to MDMA (10 mg kg-1, i.p.)
      was enhanced by quinidine pretreatment. 5. The hyperthermic response following
      MDA was greater in male DA rats, despite plasma drug concentrations being 40%
      higher in females 60 min after injection. 6. Seven days after a single dose of
      MDMA (10 mg kg-1, i.p.) there was a substantial loss in the concentration of 5-HT
      and 5-hydroxyindoleacetic acid (5-HIA) in cortex and hippocampus. [3H]-paroxetine
      binding was also decreased by 27% in the cortex, indicating that the amine loss
      reflected a neurodegenerative change. MDMA (5 mg kg-1, i.p.) was without effect
      on brain 5-HT content. content.7. A single dose of MDA (5 mg kg-1, i.p.) produced
      a major (approximately 40%) loss of 5-HT content of cortex and hippocampus 7 days
      later. The loss was similar in males and females.8 These data demonstrate that
      female DA rats are more susceptible to the acute hyperthermic effects ofMDMA,
      probably because of impaired N-demethylation and indicate that in human subjects
      acuteMDMA-induced toxicity may be exacerbated in poor metabolizer phenotypes. Low
      debrisoquine hydroxylase activity did not appear to impair the formation of a
      MDMA or MDA neurotoxic metabolite. Both severe acute hyperthermia and delayed
      neurotoxicity occurred following plasma levels of MDMA comparable to those
      reported in persons misusing the drug.

PMID- 7582555
TI  - Contribution of interleukin-1 beta to the inflammation-induced increase in nerve
      growth factor levels and inflammatory hyperalgesia.
AB  - 1. Peripheral inflammation is associated with the local production of neuroactive
      inflammatory cytokines and growth factors. These may contribute to inflammatory
      pain and hyperalgesia by directly or indirectly altering the function or chemical
      phenotype of responsive primary sensory neurones. 2. To investigate this,
      inflammation was produced by the intraplantar injection of complete Freund's
      adjuvant (CFA) in adult rats. This resulted in a significant elevation in
      interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) levels in the
      inflamed tissue and of the peptides, substance P and calcitonin gene-related
      peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. 3. The
      effects of a steroidal (dexamethasone) and a non-steroidal (indomethacin) anti
      inflammatory drug on the levels of NGF and IL-1 beta in inflamed tissue were
      investigated and compared with alterations in behavioural hyperalgesia and
      neuropeptide expression in sensory neurones. 4. Systemic dexamethasone (120
      micrograms kg-1 per day starting the day before the CFA injection) had no effect
      on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a
      reduction in mechanical and to a lesser extent thermal sensitivity occurred.
      Indomethacin at 2 mg kg-1 daily (i.p.) had no effect on the hyperalgesia and a
      dose of 4 mg kg-1 daily was required to reduce significantly mechanical and
      thermal hypersensitivity. 5. The increase in NGF produced by the CFA inflammation
      was prevented by both dexamethasone and indomethacin, but only at the higher dose
      levels. Dexamethasone at the lower and higher dose regimes diminished the
      upregulation of IL-1 beta whereas indomethacin had an effect only at the higher
      dose. 6. The increase in SP and CGRP levels produced by the CFA inflammation was
      prevented by dexamethasone and indomethacin at the lower and higher dose regimes.
      7. Intraplantar injections of IL-1 beta (0.01, 0.1 and 1 ng) produced a brief (6
      h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was
      prevented by pretreatment with human recombinant IL-1 receptor antagonist (IL-1
      ra) (0.625 microgram, i.v.). The thermal hyperalgesia but not the NGF elevation
      produced by intraplantar IL-1 beta (1 ng) was prevented by administration of a
      polyclonal neutralizing anti-NGF serum. 8. IL-1 ra significantly reduced the
      mechanical hyperalgesia produced by CFA for 6 h after administration as well as
      the CFA-induced elevation in NGF levels. Anti-NGF pretreatment substantially
      reduced CFA-induced mechanical and thermal hyperalgesia without reducing the
      elevation in IL-1 beta. 9. Intraplantar NGF (0.02, 0.2 and 2 microg) injections
      produced a short lasting thermal and mechanical hyperalgesia but did not change
      IL-1beta levels in the hindpaw skin.10. Our results demonstrate that IL-1beta
      contributes to the upregulation of NGF during inflammation and that NGF has a
      major role in the production of inflammatory pain hypersensitivity.

PMID- 7582560
TI  - Enhancing and inhibitory effects of nitric oxide on superoxide anion generation
      in human polymorphonuclear leukocytes.
AB  - 1. The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic
      nitric oxide (NO) on superoxide anion (O2-) generation were investigated in human
      polymorphonuclear leukocytes (PMNs). 2. Neither SNP (10 nM to 10 microM) nor NO
      (40 nM to 40 microM) alone induced O2- generation or change of intracellular Ca2+
      concentration ([Ca2+]i) in human PMNs. 3. Pretreatment with SNP or NO at the
      concentrations used (SNP, 10 nM to 10 microM: NO, 40 nM to 40 microM) showed a
      biphasic concentration-dependent effect on O2- generation induced by f-methionyl
      leucyl-phenylalanine (FMLP). Low concentrations of SNP (10 nM to 100 nM) and NO
      (400 nM) did not affect either basal cyclic GMP levels or cyclic GMP levels
      stimulated by FMLP, but enhanced FMLP-induced O2- generation and [Ca2+]i
      elevation. On the other hand, high concentrations of SNP (10 microM) and NO (40
      microM) alone elevated cyclic GMP levels and inhibited FMLP-induced O2-
      generation and [Ca2+]i elevation. 4. 8-Bromo-cyclic GMP (8-Br-cyclic GMP) at
      concentrations ranging from 1 microM to 1 mM did not induce O2- generation on its
      own and had little effect on FMLP-induced O2- generation and [Ca2+]i elevation.
      5. Addition of a high concentration of NO (40 microM) decreased authentic O2-
      formation by pyrogallol in a cell-free system, but a low concentration of NO (400
      nM) had no effect on this. On the other hand, addition of SNP in the
      concentration-ranges used had no effect on authentic O2- formation by pyrogallol.
      6. In this study, we have shown that SNP and NO have dual effects (enhancement
      and inhibition) on 02- generation induced by FMLP in human peripheral PMNs. The
      results suggest that the enhancement observed with SNP and NO at low
      concentrations is not mediated by activation of the guanylate cyclase-cyclic GMP
      pathway. The suppressive effect of SNP and NO at higher concentrations is
      mediated by the NO-induced O2--scavenging effect and activation of the guanylate
      cyclase-cyclic GMP pathway.

PMID- 7582562
TI  - Further evidence of anticonvulsant role for 5-hydroxytryptamine in genetically
      epilepsy-prone rats.
AB  - 1. This study was designed to evaluate further the role of 5-hydroxytryptamine (5
      HT) in regulating susceptibility and/or intensity of audiogenic seizures in
      genetically epilepsy-prone rats. 2. The effects of sertraline, a highly selective
      and potent inhibitor of 5-HT uptake, on both the intensity of the audiogenic
      seizures and the extracellular concentrations of 5-HT in the thalamus were
      evaluated in severe seizure genetically epilepsy-prone rats. 3. Sertraline (7.5,
      15 and 30 mg kg-1, i.p.) produced a dose-dependent reduction in the intensity of
      the audiogenic seizures. 4. Brain microdialysis studies showed that the same
      doses of sertraline also caused dose-dependent increases in the extracellular 5
      HT concentration in the thalamus of the freely moving rats. 5. The peak
      anticonvulsant effect correlated temporally with the peak increases in the
      extracellular 5-HT concentration for this drug. 6. It is concluded that
      enhancement of 5-hydroxytryptaminergic transmission may contribute to the
      anticonvulsant effect of sertraline in severe seizure genetically epilepsy-prone
      rats. 7. The present results coupled with earlier investigations support the
      hypothesis that 5-HT plays an anticonvulsant role in genetically epilepsy-prone
      rats.

PMID- 7582563
TI  - Characterization of receptors for kinins and neurokinins in the arterial and
      venous mesenteric vasculatures of the guinea-pig.
AB  - 1. In the present work, we have studied the microvascular reactivity of the
      arterial and venous mesenteric beds of the guinea-pig to bradykinin, neurokinins
      and other agents. 2. The vasoactive properties of three selective agonists for
      neurokinin receptors, namely [Sar9, Met (O2)11]SP (NK1), [beta-Ala8]NKA(4-10)
      (NK2) and [MePhe7]NKB (NK3), were evaluated on precontracted arterial and venous
      mesenteric vasculatures of the guinea-pig. The NK1-selective agonist,
      [Sar9,Met(O2)11]SP (1 to 1000 pmol), induced an endothelium-dependent and N omega
      nitro-L-arginine methyl ester (L-NAME)-sensitive relaxation of the arterial
      vasculature precontracted with methoxamine, whereas the NK2 and NK3-selective
      agonists were virtually inactive at high doses (1000 pmol). 3. The three
      selective neurokinin receptor agonists were inactive in the non-precontracted
      arterial and venous mesenteric vasculatures as well as in the precontracted
      venous mesenteric vasculature. 4. Bradykinin (0.1 to 100 pmol) induced a marked
      dose- and endothelium-dependent vasodilatation of the precontracted arterial and
      venous vasculatures. ED50 values were 5.5 pmol on the arterial side and 1.9 pmol
      on the venous side. In contrast, desArg9-bradykinin was inactive at doses up to
      1000 pmol. Furthermore, on the arterial and venous sides, a higher dose of
      bradykinin (1000 pmol), induced a biphasic effect, a transient constriction
      followed by a marked and sustained vasodilatation. The vasodilator effects of
      bradykinin were abolished by Hoe 140 (0.1 microM) and CHAPS, markedly reduced by
      L-NAME and were unaffected by [Leu8]desArg9-bradykinin (0.1 microM) on both sides
      of the mesenteric vasculature. Hoe 140 also abolished the arterial
      vasoconstrictions induced by high doses of bradykinin. 5. Noradrenaline,
      angiotensin II and endothelin-1 produced contractions on both sides of the
      mesenteric circulation, while acetylcholine (arterial side) and sodium
      nitroprusside (arterial and venous sides) caused vasodilatation.6. Our study
      supports the view that NK1 receptors responsible for vasodilatation are present
      solely in the endothelium of the arterial mesenteric vasculature of the guinea
      pig. On the other hand, bradykinin(0.1 to 100 pmol) exerts predominantly
      vasodilator effects on both sides of the mesenteric vasculature via selective
      activation of B2 receptors located on the endothelium. The same receptor type
      located on the smooth muscle appears to be responsible for the arterial and
      venous constriction with high doses of bradykinin.

PMID- 7582565
TI  - Inhibition of the centrally induced increases in myocardial oxygen demand in
      rabbits by chronic treatment with baclofen, a selective GABAB agonist.
AB  - 1. A previous study from our group demonstrated that neurones of the
      paraventricular nucleus of the hypothalamus (PVN) are selectively involved in the
      central control of the cardiac function. Moreover, in that study, it was shown
      that baclofen, a selective GABAB receptor agonist, is capable of modulating the
      increases in myocardial contractility and oxygen demand evoked by electrical or
      pharmacological stimulation of the PVN. Nevertheless, the acute administration of
      this compound was frequently accompanied by a cardiodepressant effect. 2. In the
      present study, the effects of a long term treatment (14 days) with baclofen (3 or
      10 mg kg-1, i.p.) have been examined on the excitatory haemodynamic responses
      evoked by central pharmacological stimulation in anaesthetized rabbits. 3. The
      i.c.v. injection of L-glutamate (3 mg kg-1) induced marked increases in dP/dtmax
      (32%), mean arterial pressure (39%) and on two indices of myocardial oxygen
      consumption: the rate-pressure product (34%) and the triple product (78%). 4.
      Baclofen blunted the positive inotropic response and the increases in myocardial
      oxygen consumption induced by L-glutamate in a dose-related manner. The higher
      dose of baclofen (10 mg kg-1, i.p.), reduced by more than 50% these excitatory
      effects of L-glutamate without eliciting any significant negative effect on basal
      haemodynamics. The same doses of baclofen were not able to blunt the hypertensive
      response induced by central stimulation. 5. These results confirm and extend our
      previous findings suggesting that it is possible to discriminate the central
      control of vasomotor tone from that of cardiac function and also that baclofen
      can modulate the latter. It is concluded that when given chronically, baclofen
      modulates the increases in myocardial oxygen demand induced by activation of the
      central nervous system in doses which do not depress the resting cardiac
      function.

PMID- 7582566
TI  - The structure of scientific revolutions: a cell transplant perspective.

PMID- 7582564
TI  - R-alpha-methylhistamine-induced inhibition of gastric acid secretion in pylorus
      ligated rats via central histamine H3 receptors.
AB  - 1. The effect of central H3 histamine receptor activation on gastric acid and
      pepsin production has been investigated in pylorus-ligated rats. 2.
      Intracerebroventricular injections (i.c.v.) of the selective H3 agonist, R-alpha
      methylhistamine (0.5-50 nmol per rat) caused a dose-dependent inhibition of
      gastric acid secretion while intravenous administration (5-500 nmol per rat) was
      completely ineffective. 3. I.c.v. microinjections of mepyramine, tiotidine and
      thioperamide (51 nmol per rat), selective antagonists at H1-, H2- and H3-sites
      respectively, failed to modify the acid secretory response to pylorus ligation.
      4. The antisecretory effect of R-alpha-methylhistamine (5 nmol per rat, i.c.v.)
      was selectively prevented by the H3-blocker, thioperamide (51 nmol per rat,
      i.c.v.), mepyramine and tiotidine pretreatment being completely inactive. 5.
      Unlike acid secretion, pepsin production was not significantly affected by all
      the tested compounds. 6. These findings provide the first pharmacological
      evidence that the activation of central H3 histamine receptors exerts a negative
      control in the regulation of gastric acid secretion in conscious pylorus-ligated
      rats.

PMID- 7582561
TI  - Relationship between inhibition of cyclic AMP production in Chinese hamster ovary
      cells expressing the rat D2(444) receptor and antagonist/agonist binding ratios.
AB  - 1. Radioligand binding assays using [3H]-(-)-sulpiride, in the presence of 1 mM
      ethylenediaminetetraacetic acid (EDTA) and 100 microM guanylylimidodiphosphate
      (GppNHp) and [3H]-N0437 were developed to label the low and high agonist affinity
      states of the rD2(444) receptor (long form of the rat D2 receptor) respectively.
      The ratios of the affinities of compounds in these two assays (Kapp [3H]-(-)
      supiride/Kapp [3H]-N-0437) were then calculated. 2. The prediction that the
      binding ratio reflected the functional efficacy of a compound was supported by
      measurement of the ability of a number of compounds acting at dopamine receptors
      to inhibit rD2(444)-mediated inhibition of cyclic AMP production. When the rank
      order of the ratios of a number of these compounds was compared to their ability
      to inhibit the production of cyclic AMP, a significant correlation was seen
      (Spearman rank correlation coefficient = 0.943, P = 0.01). 3. In conclusion, the
      sulpiride/N-0437 binding ratio reliably predicted the efficacy of compounds
      acting at dopamine receptors to inhibit cyclic AMP production mediated by the
      rD2(444) receptor.

PMID- 7582567
TI  - Immunobiology of cellular transplantation.
AB  - The goal of cellular transplantation is to allow long-term function of the
      grafted cells using minimal host immunosuppression. To this end, the major
      strategies to implant cells and tissues are through: (i) the pretreatment of the
      graft to reduce tissue immunogenicity; (ii) the application of immunoisolation
      technologies to prevent host sensitization to implanted cells; and (iii) the
      induction of immunological tolerance to the donor tissues. Further, a major
      dilemma facing clinical tissue grafting is the shortage of donor tissue for
      transplantation. This problem requires the consideration of tissues from other
      species (xenografts) as a potential source of donor material. In light of these
      issues, the focus of this discussion is on the T cell-dependent response to
      allogeneic and xenogeneic transplants and the implications of this reactivity on
      the field of cellular replacement therapy.

PMID- 7582569
TI  - Microglia: the effector cell for reconstitution of the central nervous system
      following bone marrow transplantation for lysosomal and peroxisomal storage
      diseases.
AB  - Treatment and potential cure of lysosomal and peroxisomal diseases, heretofore
      considered fatal, has become a reality during the past decade. Bone marrow
      transplantation, (BMT), has provided a method for replacement of the disease
      causing enzyme deficiency. Cells derived from the donor marrow continue to
      provide enzyme indefinitely. Several scores of patients with diseases as diverse
      as metachromatic leukodystrophy, adrenoleukodystrophy, globoid cell
      leukodystrophy, Hurler syndrome (MPS I-H), Maroteaux-Lamy (MPS VI) Gaucher
      disease, and fucosidosis have been successfully treated following long-term
      engraftment. Central nervous system (CNS) manifestations are also prevented or
      ameliorated in animal models of these diseases following engraftment from normal
      donors. The microglial cell system has been considered to be the most likely
      vehicle for enzyme activity following bone marrow engraftment. Microglia in the
      mature animal or human are derived from the newly engrafted bone marrow. Graft-v
      host disease activation of the microglia is also of importance. This article will
      summarize some of the pertinent literature relative to the role of microglia in
      such transplant processes.

PMID- 7582570
TI  - Neural transplantation.
AB  - Cell transplantation is now being explored as a new therapeutic strategy to
      restore function in the diseased human central nervous system. Neural grafts show
      long-term survival and function in patients with Parkinson's disease but the
      symptomatic relief needs to be increased. Cell transplantation seems justified in
      patients with Huntington's disease and, at a later stage, possibly also in
      demyelinating disorders. The further development in this research field will
      require systematic studies in animal experiments but also well-designed clinical
      trials in small groups of patients.

PMID- 7582568
TI  - In vivo cell transformation: neogenesis of beta cells from pancreatic ductal
      cells.
AB  - During embryogenesis, islet cells differentiate from primitive duct-like cells.
      This process leads to the formation of islets in the mesenchyme adjacent to the
      ducts. In the postnatal period, any further expansion of the pancreatic endocrine
      cell mass will manifest itself either by a limited proliferation of the existing
      islet cells, or by a reiteration of ontogenetic development. It is the latter,
      cell transformation by a process of differentiation from a multipotential cell,
      that will be referred to in this review as islet neogenesis. To better appreciate
      the mechanisms underlying islet cell neogenesis, some of the basic concepts of
      developmental biology will be reviewed. Considerable discussion is devoted to the
      subject of transdifferentiation, a change in a cell or in its progeny from one
      differentiated phenotype to another, where the change includes both morphological
      and functional phenotypic markers. While in vitro studies with fetal and neonatal
      pancreata strongly suggest that new islet tissue is derived from ductal
      epithelium, what is not established is whether the primary cell is a committed
      endocrine cell or duct-like cell capable of transdifferentiation. Next, research
      in the field of beta-cell neogenesis is surveyed, in preparation for the
      examination of whether there is a physiological means of inducing islet cell
      regeneration, and whether the new islet mass will function in a regulated manner
      to reverse or stabilize a diabetic state? Our belief is that the pancreas retains
      the ability to regenerate a functioning islet cell mass in the postnatal period,
      and that the process of cell transformation leading to islet neogenesis is
      mediated by growth factors that are intrinsic to the gland. Furthermore, it is
      our contention that these factors act directly or indirectly on a multipotential
      cell, probably associated with the ductular epithelium, to induce endocrine cell
      differentiation. In other words, new islet formation in the postnatal period
      reiterates the normal ontogeny of islet cell development. These ideas will be
      fully developed in a discussion of the Partial Duct Obstruction (PDO) Model.

PMID- 7582571
TI  - Endothelial cell transplantation.
AB  - Endothelial cells line the lumenal surface of all elements of the vascular
      system. These cells exhibit numerous metabolic functions necessary for the
      maintenance of homeostasis. The critical role of endothelium in maintaining
      normal blood vessel function is exemplified by the poor clinical performance of
      small diameter polymeric vascular grafts which fail due, in part, to the lack of
      a functional endothelium on the lumenal surface. Extensive research has explored
      the potentiality of transplanting endothelial cells onto polymeric vascular
      grafts to improve graft function. Several critical issues have been explored
      including the source of endothelial cells for transplantation, the interaction of
      endothelium with polymers and the healing process of endothelial cell
      transplanted grafts. The future of endothelial cell transplantation will also
      include the use of these cells as vehicles for genetic engineering.

PMID- 7582572
TI  - Cell transplantation and Federal regulation.
AB  - Federal regulation of tissues and organs has proceeded slowly, with main emphasis
      on safety of the procured material. More recently with the development of somatic
      cell therapies, the Food and Drug Administration has issued some guidance
      documents that establish that some classes of cells that are manufactured will be
      subject to not only safety but efficacy requirements. Cell transplantation
      presents several aspects that are similar to somatic cell therapies, and the
      purpose of this presentation is to explore those relationships.

PMID- 7582574
TI  - Normal structures on endoscopic ultrasonography: visualization measurement data
      and interobserver variation.
AB  - Endoscopic ultrasonography is a highly technical procedure requiring considerable
      experience and knowledge of human anatomy and its variations. Its use in the
      assessment of a variety of upper and lower gastrointestinal diseases has been
      valuable. Measurement of structures by endosonography is routinely accomplished
      although with uncertain accuracy, reproducibility, and interobserver variation.

PMID- 7582575
TI  - Endosonography of the pancreas: normal variation versus changes of early chronic
      pancreatitis.
AB  - The normal pancreas may have a hypoechoic ventral segment that does not correlate
      with the presence of pancreas divisum. Elderly individuals and heavy alcohol
      users may have abnormalities of their pancreas detected by EUS that are entirely
      asymptomatic. In patients with early stages of chronic pancreatitis, EUS can
      reveal abnormalities when other imaging tests including ERCP are normal.
      Determining the accuracy of EUS in diagnosing chronic pancreatitis is made
      difficult by the absence of a readily available gold standard. Whether EUS-guided
      fine needle aspiration biopsy will assist in this determination requires further
      investigation.

PMID- 7582576
TI  - Vascular anatomy: how to identify the major retroperitoneal vessels.
AB  - The anatomical relationships of retroperitoneal vessels and organs as seen from
      the stomach and duodenum with sector scan and linear array echoendoscopes are
      discussed. Methods to place and maneuver the echoendoscope in six standard,
      easily recognized positions and the withdrawn-wedged position are reviewed. From
      these positions, major retroperitoneal vessels can be investigated.

PMID- 7582577
TI  - Endoscopic ultrasound scanning of the upper gastrointestinal tract using a curved
      linear array transducer: "the linear anatomy".
AB  - During the last few years endoscopes with electronic array transducers have been
      introduced, making EUS-guided biopsy possible. However, only a few studies have
      been published with this kind of instrument. In this article, the EUS examination
      procedure and the normal anatomy of the upper gastrointestinal tract using a
      curved linear array transducer are described.

PMID- 7582573
TI  - Implantable biohybrid artificial organs.
AB  - Biohybrid artificial organs encompass all devices which substitute for an organ
      or tissue function and incorporate both synthetic materials and living cells.
      This review concerns implantable immunoisolation devices in which the tissue is
      protected from immune rejection by enclosure within a semipermeable membrane. Two
      critical areas are discussed in detail: (i) Device design and performance as it
      relates to maintenance of cell viability and function. Attention is focussed on
      oxygen supply limitation and how it is affected by tissue density and the
      development of materials that induce neovascularization at the host tissue
      membrane interface; and (ii) Protection from immune rejection. Our current
      knowledge of the mechanisms that may be operative in immune rejection in the
      presence of a semipermeable membrane barrier is limited. Nonetheless, recent
      studies shed light on the role played by membrane properties in preventing immune
      rejection, and many studies demonstrate substantial progress towards clinically
      useful implantable immunoisolation devices.

PMID- 7582578
TI  - Endoscopic ultrasonography with a curved array transducer: normal echoanatomy of
      retroperitoneum.

PMID- 7582579
TI  - Staging concepts for gastrointestinal malignancies: the importance of
      preoperative locoregional T- and N-staging.
AB  - Preoperative locoregional staging of gastrointestinal tumors is of special
      significance for evaluation of resectability that means complete tumor removal
      without residual tumor (R0-resection). This is especially important within a
      multimodal therapeutic concept including neoadjuvant therapy of nonresectable
      tumors. In esophageal cancer above the bifurcation, tumors that are staged T3 or
      T4 should have neoadjuvant radiochemotherapy in order to achieve a down-staging
      and increase the chance for a complete tumor resection. Preoperative chemotherapy
      is further established in esophageal carcinomas below the bifurcation and gastric
      carcinomas in stage T4. As in pancreatic carcinoma, neoadjuvant treatment has no
      proven indication. Preoperative locoregional staging mainly concerns the
      infiltration of retroperitoneal veins, which represents the crucial point for
      resectability. Concerning carcinomas of the lower GI tract the T- and N-staging
      is of special relevance for rectal cancer because preoperative radiochemotherapy
      in T4-stage is an accepted indication. The T- and N-staging of gastrointestinal
      tumors has important clinical consequences; the demands for accuracy of
      endosonographic examinations are therefore very high.

PMID- 7582580
TI  - Endosonographic staging of esophageal cancer: a review of literature results.
AB  - A large body of literature has accumulated showing endoscopic ultrasonography to
      be highly accurate in the locoregional staging of esophageal cancer. Several
      special aspects and problems of EUS in this setting are also presented in the
      literature. This article reviews this body of information and presents data from
      endoscopic staging research.

PMID- 7582581
TI  - Endosonographic staging of gastric cancer: a review of literature results.
AB  - This article provides an overview of the articles published on locoregional
      staging of stomach cancer by endoscopic ultrasonography. For an analysis of the
      clinical value of EUS in the diagnosis and treatment, the reader is referred to
      the review books, articles, and consensus statements that are cited.

PMID- 7582582
TI  - Interobserver variation in tumor staging.
AB  - Interobserver agreement in cardioesophageal and rectal tumor evaluation is
      generally good, especially for uT1 and uT4 tumors. Diagnosis of a uT2 tumor is
      difficult and results in poor agreement. However, the proportion of agreement is
      satisfactory for distinguishing tumors that invade the mediastinal or the
      perirectal fat from those that do not, a situation that may be the most relevant
      from a therapeutic point of view. In cases of cardioesophageal tumor, agreement
      for metastatic LN is lower and depends on the sites involved, with the best
      agreement for intra-abdominal LN, which may indicate a worse prognosis. Lack of
      agreement in EUS images can be avoided by precise manipulation of the
      echoendoscope in the upper part of the mediastinum and by improving training and
      the definitions regarding EUS.

PMID- 7582584
TI  - In vitro studies of lymph node analysis.
AB  - Endosonography has become a widely accepted diagnostic procedure in the staging
      of gastrointestinal tumors over the past 10 years. The question of whether
      endosonography is equally as effective in the diagnosis of regional lymph node
      metastases has not been conclusively answered. This article presents a brief
      review of in vitro studies of lymph node analysis in the upper and lower
      gastrointestinal tract.

PMID- 7582585
TI  - Endoscopic ultrasonography-guided puncture of the lymph nodes: first experience
      and clinical consequences.
AB  - Endoscopic ultrasonography with fine needle aspiration is indicated for
      assessment of lymph node metastases as well as malignant tumor diagnosis. This
      technique has an accuracy of about 80%. There have been no reported
      complications. Improvement in needles and techniques will improve overall
      results.

PMID- 7582586
TI  - Detection of anastomotic recurrence by endoscopic ultrasonography.
AB  - There seems little doubt that endoscopic ultrasonography is highly sensitive and
      significantly better than computed tomography for the diagnosis of recurrent
      cancer at the surgical anastomosis after resection of esophageal and gastric
      cancer. The impact of using EUS for this purpose is discussed.

PMID- 7582588
TI  - Endoscopic ultrasonography in upper gastrointestinal submucosal tumors: a
      literature review.

PMID- 7582587
TI  - Restaging after radiotherapy and chemotherapy: value of endoscopic
      ultrasonography.
AB  - The outcome in gastroenterological tumors is determined by many factors.
      Prospective studies are required to prove the clinical value of endoscopic
      ultrasonography. Endoscopic ultrasonography as a staging tool may have only
      indirect influence on the outcome by providing potentially better selection
      criteria for the application of different treatments that are stage dependent.

PMID- 7582589
TI  - Puncture of submucosal and extrinsic tumors: is there a clinical need? Puncture
      techniques and their accuracy.
AB  - Cytological or histological tissue diagnosis of submucosal and extrinsic tumors
      adjacent to the upper gastrointestinal tract is required in many patients for
      differentiation of benign and malignant lesions. In the case of a submucosal
      lesion, it can be most efficiently obtained by transendoscopic needle puncture
      using a conventional endoscope and a guillotine needle device sampling
      histological tissue specimen. In the case of an extrinsic paraesophageal mass
      lesion in the dorsal mediastinum, transmural EUS-guided fine needle aspiration
      puncture appears to be an efficient technique for the differentiation of benign
      and malignant lesions. However, for transgastral or transduodenal EUS-guided FNA
      puncture, especially of pancreatic tumors, new prototypes of aspiration catheters
      with an extending steel needle are mandatory to obtain diagnostic tissue
      specimens.

PMID- 7582583
TI  - Assessment of resectability of gastrointestinal cancers by endoscopic
      ultrasonography.
AB  - The general principle in the treatment of malignancy is complete tumor removal.
      Meticulous preoperative staging determines whether the complete resection is
      technically possible. Should radical resection prove to be impossible, palliative
      methods are applied that aim at restitution of the intestinal passage without any
      effect on survival.

PMID- 7582590
TI  - Cost-effectiveness of endoscopic ultrasonography in submucosal tumors.
AB  - Clinical management decisions are increasingly based on endoscopic
      ultrasonography, especially in esophageal or rectal malignancies and unclear
      submucosal tumors. Studies investigating the impact of different diagnostic
      approaches on economic resources and cost effectiveness, however, have emerged
      only very recently. In this article, we have compared an approach using EUS
      versus one using computed tomography in further evaluating unclear submucosal
      tumors of the upper gastrointestinal tract with regard to incremental costs per
      patient.

PMID- 7582591
TI  - Primary achalasia: analysis of endoscopic ultrasonography features with different
      instruments.
AB  - The examination of patients with primary achlasia using classical radial
      endoscopic ultrasonography lacks accuracy and has yielded inconclusive results.
      The diameter of the scope and the presence of a balloon makes examination of a
      short stenotic segment difficult. These techniques, however, are useful in the
      evaluation of patients with suspected pseudoachalasia due to tumor infiltration.

PMID- 7582593
TI  - Gastroesophageal reflux and Barrett's esophagus.
AB  - The role of endoscopic ultrasonography in the assessment of patients with reflux
      esophagitis and Barrett's esophagus is the subject of intense evaluation. Many
      tests have been proposed for the evaluation of patients with acid-reflux
      disorders. However, in the current era of cost containment, it is reasonable to
      perform only those tests necessary to provide the information required for
      optimal patient management. Although the role of EUS in evaluating patients with
      Barrett's esophagus appears promising, its clinical use remains largely unproven.

PMID- 7582592
TI  - The use of high frequency endoscopic ultrasonography probes in the evaluation of
      achalasia.
AB  - Because its ultrasound beam cannot penetrate beyond a radius of 2 cm, HRES is
      limited in evaluating abnormalities within or adjacent to the esophageal wall. To
      date, however, it has provided new diagnostic capabilities in evaluating patients
      with several different esophageal disorders. EUS at lower frequencies has shown
      inconsistent results in evaluating the thickness of esophageal muscle layers in
      patients with achalasia. HRES has been able to more accurately measure the
      individual CSM, LSM, and TM layers of the muscularis propria and the mean
      measurements have been noted to increase in achalasia patients when compared with
      normals. HRES has been found to be clinically useful in assessing histologic
      damage following pneumatic dilatation and in localizing the LES during the
      administration of intrasphincter botulinum toxin injection in the treatment of
      achalasia.

PMID- 7582594
TI  - Portal hypertension: review of data and influence on management.
AB  - It is evident that endoscopic ultrasonography could have a great clinical role in
      the selection of the best treatment for the individual patient because it allows
      the simultaneous visualization of a large part of the portal venous system and
      its collaterals. It has not been shown that the same kind of treatment is
      suitable for every patient with portal hypertension, and failure of a particular
      treatment may be attributable to an incorrect selection of patients. Further
      perspective studies with EUS in patients with portal hypertension are thus
      necessary in order to clearly state the cost-benefit of this technique in the
      management of these subjects.

PMID- 7582595
TI  - Portal hypertension: influence on management.
AB  - In treating cases of portal hypertension, it is important to know the intramural,
      extramural, and communicating vascular structures of the esophagus and stomach
      using EUS. From these structures, suitable treatment for the esophagogastric
      varices can be selected and the efficacy of treatment can be evaluated.

PMID- 7582596
TI  - Gastric ulcer: can endoscopic ultrasonography predict healing?
AB  - The course of healing of gastric ulcers and their relapse were examined, based on
      observation of the cross-sections of gastric ulcers using endoscopic
      ultrasonography. This study concludes that EUS can predict ulcer healing and it
      is suggested that the strategy be planned based on the findings from EUS.

PMID- 7582597
TI  - Large gastric folds evaluated by endoscopic ultrasonography.
AB  - Diffuse large gastric folds may lead to difficult clinical diagnosis particularly
      in biopsy-negative cases. In the differential diagnosis Menetrier's disease or
      hypertrophic gastritis and linitis, EUS is very helpful because of its ability in
      imaging the location of mural abnormality. In initially negative biopsy for
      linitis, EUS can help the clinician in selecting the optimal site for positive
      biopsy. In gastric NHL, EUS can be helpful in selecting the appropriate candidate
      for surgery and in monitoring the response to chemotherapy and irradiation. EUS
      appears to be more suitable for TNM staging than the Ann Arbor classification for
      gastric NHL. The routine use of EUS-guided FNA should be attempted for obtaining
      the tissue diagnosis.

PMID- 7582598
TI  - A simple approach to the design of a shielded gradient probe for high-resolution
      in vivo spectroscopy.
AB  - A simple approach to the design of a shielded gradient coil set for a high
      resolution NMR probe is described in detail. An Appendix is provided that shows
      the step-by-step Mathematica routine used to carry out the necessary
      calculations. The probe provided excellent water suppression and gradient
      accelerated acquisition of one- and two-dimensional spectra from perfused bovine
      retina.

PMID- 7582599
TI  - Yield enhancement of a double-quantum filter sequence designed for the edited
      detection of GABA.
AB  - To overcome limitations in the signal to noise ratio (S/N) of previously proposed
      multiple-quantum filters (MQFs), designed for editing the GABA A2 multiplet from
      the creatine (Cr) singlet in proton spectroscopy of brain, a new double-quantum
      filter is proposed which significantly enhances S/N (thereby making it comparable
      with the spin-echo difference editing technique) while maintaining the superior
      Cr suppression and zero vulnerability to subtraction errors of previously
      proposed MQFs. The S/N enhancement results primarily from a significant reduction
      in transverse-relaxation losses, achieved by shortening the filter sequence by
      approximately 70%, first by altering the criterion that determines the initial
      evolution period and, second, by effectively eliminating the refocusing time
      prior to the start of acquisition. The altered evolution time criterion also
      leads to an increase in the intrinsic yield of the filter from 25 to 39%. The
      analysis of the filter design was verified in vitro on phantoms of GABA in D2O,
      and the maintenance of editing capability, i.e., Cr suppression by more than
      1600, was demonstrated on rat brain extracts.

PMID- 7582600
TI  - Spectral editing with adiabatic pulses.
AB  - Amplitude- and frequency-modulated pulses, known as adiabatic pulses, can induce
      uniform flip angles in the presence of extreme B1 inhomogeneity, which makes them
      advantageous for in vivo surface-coil studies. This paper describes the
      conversion of conventional (square pulse-based) spectral-editing sequences into
      their adiabatic counterparts. Eight adiabatic homo- and heteronuclear sequences
      are experimentally evaluated for lactate editing. For homonuclear lactate
      editing, gradient-enhanced multiple-quantum-coherence filtering provides the best
      overall performance (100% signal recovery with excellent water and lipid
      suppression in a single acquisition). For heteronuclear [3-(13)C]lactate editing,
      gradient-enhanced heteronuclear multiple-quantum-coherence filtering provides the
      best suppression of unwanted signals in a single acquisition, whereas J-modulated
      spin-echo sequences yield maximum sensitivity.

PMID- 7582602
TI  - Same-scan acquisition of both edited J-coupled multiplets and singlet resonances
      of uncoupled spins for proton MRS.

PMID- 7582603
TI  - Two-dimensional nuclear magnetic resonance method for identifying the HN/N
      signals of amino-acid residues following glycine.

PMID- 7582601
TI  - Long-range 4J and 5J, including interglycosidic correlations in gradient-enhanced
      homonuclear COSY experiments of oligosaccharides.
AB  - Gradient-enhanced, two-dimensional, homonuclear correlation techniques (GCOSY) of
      carbohydrates provide numerous correlations based on 4J and 5J long-range
      interactions. Intraresidue correlations, involving all 1H resonances of a given
      pyranose ring with its anomeric proton, are consistently observed in alpha
      pyranosyl residues at approximately 5 to 10 times lower intensities than vicinal
      3J correlation cross peaks. beta-Anomers, pyranosyl residues with axial H1
      protons, show very few such effects. Both alpha and beta anomers do, however,
      exhibit interresidue 4J correlations across the glycosidic linkage as shown for
      several linear and branched oligosaccharides ranging from three to five residues
      and are especially useful for spectral assignments in the envelope of pyranosyl
      ring protons located in the typically very crowded 3 to 4 ppm region. These
      effects depend on the strength and duration of the applied gradients.

PMID- 7582604
TI  - Transportation disasters--a review.

PMID- 7582605
TI  - The acute psychological impact on survivors following a train accident.
AB  - Sixty-six passengers surviving a collision of two trains were investigated
      concerning relevant background data, degree of personal injury, experience of a
      threat to life, symptoms and problems immediately after the accident, and
      thoughts about difficulty in coping. The most obvious impact on the survivors was
      the experience of being close to death. One result of this was that they
      developed a new coping strategy to minimize emotional pain. Some survivors also
      suffered problems of "re-living" the accident. This is important for the coping
      process. The process includes psychological integration of the accident as an
      important life event. The findings indicate that "re-living" of the accident
      through nightmares and intrusive thoughts is responsible for problems in carrying
      out ordinary tasks. The observations are in accordance with those made after
      other types of accidents and disasters.

PMID- 7582607
TI  - The Kings Cross fire: psychological reactions.
AB  - The psychological reactions of 50 survivors of the King's Cross fire, which hit
      London's underground railway system on the 18th day of November 1987, are
      described. Results are presented for the Impact of Event scale, the General
      Health Questionnaire (28-item version), the Eysenck Personality Questionnaire and
      a King's Cross Event Schedule. These are investigated in relation to (a) validity
      measures, (b) relationships between exposure and personality, and (c) spontaneous
      de-briefing. Two thirds of the sample had significant levels of psychological
      distress (meeting the "caseness" criterion on the GHQ). Both personality
      (neuroticism and L-scale) and degree of trauma exposure were related to
      subsequent reaction. Spontaneous debriefing was associated with subjective
      benefit. Transportation disasters present particular problems in relation to
      research and service delivery.

PMID- 7582608
TI  - Confrontations with reality: crisis intervention services for traumatized
      families after a school bus accident in Norway.
AB  - In August 1988 a Swedish schoolbus with 23 children and 11 adult passengers
      crashed into a tunnel wall in Norway. Twelve children and four parents died, 18
      of the passengers survived. The victims' relatives (parents, spouses, siblings,
      and others) were transported to Norway and given a "confronting" support program
      at the University hospital in Bergen. The crisis intervention program is
      described: how the relatives were helped to confront and actively cope with some
      of the stressful situations from which traumatized families very often are
      protected. One year later 42 of the relatives answered a questionnaire evaluating
      the confronting support program that was offered during their stay in Norway. A
      majority of the respondents did not regret their participation in the program.
      The answers indicate that passivity and helplessness can be counteracted through
      a combination of confrontation with reality and emotional support.

PMID- 7582609
TI  - Childhood sexual abuse as a precursor to depression and self-destructive behavior
      in adulthood.
AB  - Childhood sexual abuse (CSA) as a predictor of depression and self-destructive
      behaviors in adulthood was examined relative to other traumatic stressors in
      childhood and adulthood with special attention to sex differences. In a college
      sample of 173 men and 265 women, 16% of male (n = 28) and 24% of female
      respondents (n = 63) reported having been sexually abused as children. CSA,
      ranging from unwanted kissing and fondling to unwanted sexual intercourse,
      predicted depression, chronic self-destructiveness, self-harm ideation, acts of
      self-harm, suicide ideation, and suicide attempts, for both men and women. The
      more frequent and severe the sexual abuse and the longer its duration, the more
      depression and self-destructiveness reported in adulthood. Other stressors
      predicted these effects less consistently but their occurrence in combination
      with CSA contributed to the negativity of long-term outcomes. Study results
      affirm previous findings of a relationship between CSA and depression and self
      destructiveness in adult females and extend them to males.

PMID- 7582606
TI  - Post-traumatic morbidity in a civilian community of litigants: a follow-up at 3
      years.
AB  - This paper examines post-traumatic morbidity in a community sample who had
      claimed compensation and been assessed 10-14 months after the Lockerbie Disaster.
      At 36 months 25 residents were reassessed by clinical interview and 35 by
      questionnaire. A chronic pattern of morbidity was found in 56% of this sample
      with the most frequent diagnoses being post traumatic stress disorder and
      depression, followed by other anxiety disorders. Only six cases were found to
      have "recovered" and there was only one case of delayed onset morbidity between
      12 and 36 months. No unequivocal predictors of the presence of diagnosis or
      questionnaire scores were found.

PMID- 7582610
TI  - Smoking in Vietnam combat veterans with post-traumatic stress disorder.
AB  - The present study investigated smoking prevalence, smoking motives, demographic
      variables and psychological symptoms in 124 help-seeking, male Vietnam combat
      veterans with post-traumatic stress disorder (PTSD). A high percentage of these
      veterans smoked (60%). Vietnam veterans with PTSD who smoked were more likely
      than those who did not smoke to report higher levels of PTSD symptoms, depression
      and trait anxiety. Increased depression was associated with increased automatic
      smoking. Smokers reported a high frequency of smoking in response to military
      memories. Implications for smoking interventions, cessation, and relapse
      prevention efforts are discussed.

PMID- 7582612
TI  - A different opinion regarding the use of opiate antagonists in PTSD: comments on
      "An unusual reaction to opioid blockade with naltrexone in a case of post
      traumatic stress disorder".

PMID- 7582611
TI  - Psychological assessment of postdisaster class action and personal injury
      litigants: a case study.
AB  - The case study method is used to describe psychological assessments undertaken
      with victims of a combined natural/technological disaster for litigation
      purposes. A class action suit was filed in which the authors determined levels of
      traumatic stress in 27 plaintiffs as a group and relative to each other. The
      process was effective--the case was settled out of court in favor of the
      litigants. Individual litigants were satisfied with monetary awards received.

PMID- 7582613
TI  - Searching the traumatic stress literature using PILOTS and PsycLIT.

PMID- 7582614
TI  - PILOTS (Published International Literature on Traumatic Stress) database.

PMID- 7582615
TI  - Role of mycotoxins in human and animal nutrition and health.
AB  - The impact of mycotoxins on human and animal health is now increasingly
      recognised. Mycotoxin entry to the human and animal dietary systems is mainly by
      ingestion but increasing evidence also points at entry by inhalation. Mycotoxins
      exhibit a wide array of biological effects and individual mycotoxins can be
      mutagenic, carcinogenic, embryotoxic, teratogenic, or oestrogenic. Average levels
      of ingestion of currently known mycotoxins in most EEC countries are rather low.
      Little is known about the consequences to humans of such mycotoxin intakes.
      Establishing a causal relationship between mycotoxin exposure and human disease
      is complicated by uncertainties associated with human epidemiological studies.
      Analysis of mycotoxin adducts in human populations can act as a surrogate for
      human genotoxicity. Mycotoxins can also be immunosuppressive and appear to
      involve cellular immune phenomena and non-specific humoral factors associated
      with immunity.

PMID- 7582616
TI  - Fumonisins: their implications for human and animal health.
AB  - Fusarium moniliforme is one of the predominant fungi associated with corn
      intended for human and animal consumption world-wide. Fumonisins, food-borne
      carcinogens that occur naturally in corn, were first isolated and chemically
      characterized in South Africa in 1988. The major metabolite, fumonisin B1 (FB1),
      was subsequently shown to cause leukoencephalomalacia (LEM) in horses, pulmonary
      edema syndrome (PES) in pigs, and liver cancer in rats. FB1 is also a cancer
      promoter and initiator in rat liver; hepatotoxic to horses, pigs, rats, and
      vervet monkeys; cytotoxic to mammalian cell cultures; and phytotoxic to several
      plants. Fumonisins in home-grown corn have been associated with an elevated risk
      for human esophageal cancer in Transkei and China. There is a close structural
      similarity between fumonisin and sphingosine, and fumonisins are the first known
      naturally occurring inhibitors of sphingolipid biosynthesis. The natural
      occurrence of FB1, together with FB2 and FB3, has been reported in commercial
      corn and/or corn-based feeds and foods from Argentina, Australia, Brazil,
      Botswana, Bulgaria, Canada, China, Egypt, France, Italy, Japan, Kenya, Hungary,
      Nepal, Peru, South Africa, Switzerland, United States, and Zimbabwe. It is
      imperative that safe levels of fumonisins in human foods and animal feeds should
      be determined and realistic tolerance levels established as soon as possible.

PMID- 7582617
TI  - Economic losses and decontamination.
AB  - Mycotoxin contamination of crops may cause economic losses at all levels of food
      and feed production including crop and animal production, and crop distribution
      and processing. The national economy would be affected adversely by losses
      incurred by crop and livestock producers and the multiplier effect this has on
      other industries as a result of the reduced spending power of producers. Costs of
      chemical analyses, quality control and regulatory programs, research and
      development, extension services, law suits, and the cost of human illnesses must
      all be borne by the national economy. The value of the losses encountered depends
      on grain, animal, and animal product prices, interest rates, degree of
      contamination, and other economic variables. Even during favourable seasons it is
      likely that millions of dollars are lost as a result of the contamination of
      crops with mycotoxins. Many compounds and treatments have been tested in order to
      reduce mycotoxin concentrations in food and feed or to alleviate their adverse
      effects on animals. Some of these treatments show promising prospects for
      commercial application, while others have had commercial applications already.
      However, until reliable, cost-effective, commercially applicable methods are more
      widely available, problems associated with mycotoxin contamination and the
      economic losses resulting, will continue to be seen in food and agriculture
      industries.

PMID- 7582618
TI  - Selective chemisorption and detoxification of aflatoxins by phyllosilicate clay.
AB  - Practical and effective strategies for the detoxification of aflatoxins are
      critically needed. We have shown that a phyllosilicate clay (HSCAS): i) tightly
      binds aflatoxins in aqueous solutions, including milk; ii) markedly decreases the
      bioavailability of radiolabeled aflatoxins; iii) greatly diminishes aflatoxicosis
      in young animals, i.e., rats, chickens, turkeys, lambs, and pigs; and iv) reduces
      the level of aflatoxin M1 in the milk from lactating dairy cattle and goats. In
      further studies, ligands with one or more of the functional groups in common with
      aflatoxin were reacted with HSCAS in vitro in an attempt to elucidate the
      specificity and mechanism of tight binding (or chemisorption). A chemisorption
      index (C alpha) was developed, allowing for direct comparison of various clay and
      zeolitic minerals with HSCAS. Chemisorption indices were determined by HPLC
      analysis of extracts of the supernatants and sorbed pellets (exhaustively
      extracted with methanol and chloroform). The beta-dicarbonyl system of aflatoxin
      was found to be essential for tight binding by HSCAS. Comparison of the
      chemisorption indices from various classes of compounds with spectral data
      (DRIFTS) indicated that the molecular mechanism of aflatoxin binding may involve
      the chelation of metal ions in HSCAS with the beta-dicarbonyl moiety in
      aflatoxin. Computer modeling was utilized to provide additional information.
      Preliminary evidence suggests that aflatoxin B1 may react at surfaces and within
      the interlayers of HSCAS particles. With knowledge of the mechanism involved, it
      has been possible to further enhance the propensity of HSCAS for aflatoxins.

PMID- 7582620
TI  - Toxicological data needed for safety evaluation and regulation on inherent plant
      toxins.
AB  - Although the awareness that natural compounds in foodstuffs can have implications
      for human health is growing, there is a lack of data on the toxicology and
      occurrence. To enable the safety evaluation of inherent plant toxins adequate
      toxicological data are necessary. Of most inherent plant toxins at best only
      limited toxicological data are available, which makes it impossible to perform an
      accurate safety evaluation. This limited knowledge of inherent plant toxins
      permits the mystical claim of safety on the basis of history of food use, and
      thus the development of specific food safety regulation has been postponed. To
      further develop flexible and adequate regulation, for at least some inherent
      plant toxins, an adequate set of toxicological data should be available in order
      to verify and validate the initial regulation. Several problems (e.g.,
      availability of the plant toxin or accuracy of historical human toxicity data)
      which arise when gathering the necessary data and the development of regulations
      are discussed and elaborated with a few examples such as solanum alkaloids and
      glucosinolates. As long as nobody is held responsible to study safety aspects of
      inherent plant toxins, the lack of data will persist. Therefore a certain level
      of regulation should be recommended to provide the data needed. Such safety
      research projects integrated with new agricultural developments should be
      endorsed by the European Union and other international bodies.

PMID- 7582622
TI  - Natural toxins and protective factors in brassica species, including rapeseed.
AB  - Many plant secondary metabolites exhibit a wide range of dose-related
      physiological properties when included in the diet of animals and man. Within the
      brassica family, the glucosinolates, a group of sulphur-containing glucosides
      have been the subject of a vast amount of study and the effects of dietary
      inclusion of such compounds or their metabolites on the health of animals and man
      are briefly reviewed. Although excessive amounts of glucosinolates in animal feed
      formulations may reduce growth and performance as well as affecting thyroid,
      liver, and kidney function, there is little evidence of such effects in man. On
      the contrary, compounds derived from glucosinolates as a consequence of enzymic
      breakdown or metabolism have been shown to activate mechanisms which moderate or
      reverse carcinogenic processes. Such effects may contribute to the net anti
      carcinogenic benefit attributed to these vegetables in numerous epidemiological
      studies.

PMID- 7582623
TI  - Anti-nutritional factors of Datura in feedstuffs.
AB  - Soybean seed, linseed, some cereals seeds, and their by-products are infected by
      Datura seed weed of different varieties. The most common Datura spp. noxious to
      the farm animals are D. stramonium (atropine alkaloid) and D. ferox (scopolamine,
      98-100% of total alkaloids) mainly present in Europe and South America,
      respectively. The presence of alkaloids from Datura seeds in feedingstuffs may be
      responsible for chronic and/or subclinical toxic effects; acute poisoning from
      Datura seeds are rare. Pigs are the most sensitive animals to Datura poisoning,
      followed by cattle, horses, and chickens. Sheep and rabbits are indifferent to
      atropine presence in food because they synthesize the atropine esterase enzyme.
      The progressive atropine poisoning in pigs leads to a reduction of feed intake
      and growth, gastrointestinal motility and secretory activity, extreme mouth
      dryness, increased respiration and cardiac rate, pupil dilation, etc. Clinical
      symptoms are partly similar among different species. Toxic effects from Datura
      alkaloids presence in feeds showed possible variability of alkaloids content
      tolerated by pigs. In our recent trials, the threshold limit in pigs (20-60 kg
      live weight) was 1.5 mg alkaloids/kg of feed (1.21 mg alkaloids/kg l.w.75).

PMID- 7582621
TI  - Directly toxic effects of plant chemicals which may occur in human and animal
      foods.
AB  - Pyrrolizidine alkaloids are among the most significant plant chemicals causing
      disease in animals and humans. After absorption from the gut, the compounds are
      converted to electrophilic pyrroles in the liver which, apart from causing damage
      to this organ, may escape to cause injury to extraheptic tissues such as the
      lungs, heart, and kidneys. A group of compounds more recently found to be
      associated with neurotoxicity are various polyhydroxyalkaloids which are able to
      interfere with polysaccharide metabolism. They are able to inhibit lysosomal
      monosaccharidases by virtue of their structural resemblance to the transition
      state of particular sugar molecules. The resulting lysosomal storage diseases
      have pathology identical to that of the respective congenital and heritable
      lysosomal storage diseases which occur in animals and humans. Consumption of
      cycad plants by cattle may cause a neurotoxicity characterised mainly by a
      posterior sensory ataxia. In recent years, cycads are considered to be a risk
      factor for a spectrum of progressive neuro degenerative diseases of humans in the
      Western Pacific region. The known toxins in the plant are the methylazoxymethanol
      glycosides which are hepatotoxic and carcinogenic, and the neurotoxic non-protein
      amino acid beta-methylaminoalanine. A plant carcinogen which can be of great
      abundance in the nutritional environment is the illudine norsesquiterpene
      glucoside ptaquiloside which is found in bracken fern. This is the only plant
      carcinogen which causes natural outbreaks of bladder and/or intestinal cancer in
      livestock. Many legumes contain phytooestrogens, notably isoflavones. Consumption
      of these compounds at high levels by sheep can cause extensive lesions of the
      genitalia of females and castrated males.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582624
TI  - BCR- and M&T-activities in the area of mycotoxin analysis in food and feedstuffs.
AB  - In order to avoid undesirable side effects such as high contents of mycotoxins in
      food and feed, measurements at critical steps of the food and feed production
      chain are performed. These measurements need to be accurate and precise to
      satisfy these aims. The accuracy and precision requirements to measurements form
      the basis of the Bureau Communautaire de Reference (BCR)-and Measurements and
      Testing (M&T)-Projects. Such projects aim to improve and/or develop analytical
      methodology, sampling plans, to harmonise agreement of results between European
      Union Member States and to prepare suitable certified reference materials (CRMs).
      The selection of the matrix CRMs and their corresponding level of mycotoxin
      contamination is made on the basis of requirements of the applied analytical
      procedures, stability requirements, regulations, norms, and inter-or intra-trade
      agreements which are in relation to quality specifications of imported and/or
      exported goods. The availability of appropriate matrix CRMs is not only a
      prerequisite for the implementation of directives and norms. It allows the
      validation of new methods and provides a possible solution to trade disputes,
      means for the statistical control of analytical results, tools for laboratory
      accreditation, and it is the basis for harmonisation and traceability of
      proficiency schemes.

PMID- 7582619
TI  - Toxicity and metabolism of ochratoxin A.
AB  - The frequent occurrence of ochratoxin A (OA) in food and feed commodities and the
      high incidence of human exposure, as confirmed by different surveillance studies
      initiated several investigations devoted to elucidating the molecular mechanisms
      underlying OA toxicity. Previous studies indicated that the primary effects of OA
      are the inhibition of tRNA synthetase, the inhibition of mitochondrial
      respiration, and a disturbance of intracellular calcium homeostasis inherent to
      lipid peroxidation processes. We here report the effect of OA on a number of
      toxicological endpoints including cytotoxicity in different cell lines and
      effects on macromolecular synthesis and cell proliferation in primary cultures of
      hepatocytes at concentrations corresponding to overall exposure levels. These
      studies provide evidence that prominent toxicological effects might be linked to
      biotransformation processes. Analysis of hepatic biotransformation resulted in
      the detection of a number of distinct stable OA-metabolites. As metabolic
      activation has also been identified as an essential step in OA mutagenicity, the
      biological relevance on this mechanistic data is discussed.

PMID- 7582625
TI  - Overview on community legislation in the field of official control of mycotoxins
      in feedingstuffs.
AB  - The Community legislation currently in force identifies a group of substances
      whose presence in feedingstuffs is undesirable. For each one of these substances,
      acceptable maximum levels have been fixed. The compliance with these levels in
      feedingstuffs must be checked by Community sampling and analysis methods. In the
      specific case of the aflatoxins, analytical methods, based on thin-layer
      chromatography (TLC) and high performance liquid chromatography (HPLC), have been
      adopted by directive. Another directive has established a general sampling
      method. The practice, however, has shown that it is not applicable to very large
      batches where the distribution of the contaminants is not homogeneous. A small
      group of experts of the Commission reached the conclusion that, in the future
      Community legislation, it will be appropriate: i) to divide the undesirable
      substances in two groups (substances with homogeneous and non-homogeneous
      distribution); ii) to adopt two different strategies for the cargoes "at risk"
      and "not at risk"; iii) to have methods of sampling, preparation, and analysis
      which are fast, reliable, easy to apply, and recognized at the international
      level. These experts proposed adaptations in the directive on "Sampling," in the
      case of large vessels, but suggested at the same time deferring any decision to
      the near future.

PMID- 7582628
TI  - Occurrence of fumonisins in Europe and the BCR--measurements and testing
      projects.
AB  - Fumonisins are mycotoxins mainly produced by Fusarium moniliforme, one of the
      most prevalent seed-borne fungi of maize. Strains of Fusarium moniliforme
      isolated from cereals in Europe produced in cultures high levels (up to 4 mg/g)
      of fumonisins B1 and B2 (FB1 and FB2). FB1 and FB2 have been found in maize and
      maize-based foods and feeds in most European countries. In Italy these mycotoxins
      have been directly involved in a fatal outbreak of equine leukoencephalomalacia,
      and have been found at different levels in most maize-based food products,
      including polenta--a staple food in a region with high incidence of esophageal
      cancer. The European Commission, Community Bureau of Reference (BCR) and
      Measurements and Testing Programme (M&T), has undertaken two consecutive
      intercomparison studies, involving over 20 laboratories from 12 European
      countries, to improve the quality of fumonisins analysis at European level. The
      first study consisted in the evaluation of the determination of fumonisins in an
      unknown solution, while the second one involved the analytical methodology for
      fumonisins in contaminated and blank maize samples. A definite improvement in the
      performance of the different laboratories has been observed in the second study.
      In view of the production of reference materials certified for their fumonisins
      contents, new analytical procedures need to be developed.

PMID- 7582626
TI  - Design of sampling plans for mycotoxins in foods and feeds.
AB  - The control of the occurrence of mycotoxins in foods and feeds requires effective
      surveillance and quality control procedures which facilitate the identification
      and control of the mycotoxin problem respectively. Surveillance and quality
      control procedures involve a sequence of sampling, sample preparation, and
      analysis steps; and the integrity of the data produced by these procedures will
      be determined by the effectiveness of these steps. It is imperative that the
      sampling step is performed as accurately as possible so that the sample collected
      is representative of the batch of food or feed under investigation. Needless to
      say, the collection of a biased sample will completely invalidate the resultant
      analytical data. Most attempts to develop effective sampling protocols have
      focused upon the aflatoxins, since the majority of current regulations are
      concerned specifically with this group of mycotoxins. However, the design of
      effective sampling protocols has been severely hindered by the highly skewed
      distribution of the aflatoxins in foods and feeds. Studies already performed
      indicate that representative samples of commodities, composed of large particles
      (e.g., corn and oilseed kernels) should be 10 kg in weight, at least, and
      composed of approximately one hundred incremental samples. Similar studies have
      indicated that samples of oilseed cakes and meal, however, should be composed of
      fifty incremental samples which afford a composite sample of approximately 5 kg
      in weight.

PMID- 7582627
TI  - Analysis of mycotoxins in food and feed: certification of DON in wheat and maize.
AB  - Worldwide there are either statutory limits or in some instances advisory
      guidelines for the maximum levels of mycotoxins in foods and feeds. These limits
      which have been agreed for the protection of human health and as standards for
      trade are often set at surprisingly low levels in view of both the problems of
      sampling and the abundant evidence of the difficulties of mycotoxin analysis,
      particularly so when approaching the limits of detection. Improved methodology
      for mycotoxins and improvements in performance even of expert laboratories have,
      however, been achieved through intercomparison exercises organised by the EC
      Measurement and Testing programme (formerly BCR). On a wider scale, participation
      in proficiency testing through schemes such as the UK Food Analysis Performance
      Assessment Scheme (FAPAS) have indicated that between 10 and 40% of laboratories
      experience difficulties in obtaining satisfactory results in monitoring
      mycotoxins. Reference materials provide an important means of checking method
      performance. BCR has made a unique contribution in the production and
      certification of maize and wheat reference materials naturally contaminated with
      the Fusarium mycotoxin 4-deoxynivalenol (DON), which has now been available for
      purchase for some 2 years.

PMID- 7582629
TI  - Ochratoxin A in cereals and the BCR-M&T-projects.
AB  - Reliable analytical procedures and certified reference materials are essential
      for the establishment and enforcement of tolerance levels for ochratoxin A in
      foods. The inadequacy of analytical procedures, together with the need for
      certified reference materials, led the Commission of the European Communities
      Community Bureau of Reference (BCR) to undertake a project to prepare suitable
      reference materials for ochratoxin A in wheat, in order to improve methodology
      and to harmonise agreement of results between member states. The first
      intercomparison study indicated problems in the analysis due to the influence of
      co-extractives in the matrix, and demonstrated that further work was necessary to
      improve recovery, clean-up and reproducibility. The second intercomparison study,
      in the EC Measurements and Testing Programme, correlated the performance of the
      different methods for ochratoxin A measurement in a separate batch of
      contaminated wheat, and compared novel immunoaffinity column methods with the
      standard laboratory methods. Results were obtained from 26 laboratories within 11
      European countries, which therefore gives a good representation of the scope of
      methods currently used in Europe. Considerable improvements in the determination
      of ochratoxin A were noted compared with the first intercomparison study.

PMID- 7582633
TI  - Measurement of glucosinolates in rapeseeds.
AB  - Several ring tests have been organized by the International Organisation for
      Standardization (ISO) and the Measurement and Testing Programme (BCR) for
      improving glucosinolate methods. Finally, HPLC of desulphoglucosinolates is
      recommended by ISO, the European Committee for Standardization (CEN), and the
      European Commission (EC) as the official method. X-ray fluorescence has also
      become particularly common for fast analysis. After checking stability of intact
      glucosinolates in whole rapeseeds, the BCR has three reference materials (CRM
      366, CRM 190, CRM 367) available, certified for their total glucosinolate and
      sulphur contents. Currently, the Measurement and Testing Programme is supporting
      a research project concerning the stability of desulphoglucosinolates and intact
      glucosinolates extracts. At the present time, best results are observed with
      lyophilized extracts sealed in brown glass ampoules and stored at -18 degrees C.

PMID- 7582630
TI  - Keeping the mycotoxins out: experience gathered by an international food company.
AB  - As early as the mid-1960s the analysis of aflatoxins became an important part of
      Nestle's quality control programme, especially since the Company's products
      include a wide variety of milk- and cereal-based foods intended for infants and
      children. At that time, dealing with this problem was hampered by the lack of
      simple and reliable analytical methods, the absence of legal provisions in many
      countries, the widely different origin of the raw materials, and the fact that
      sources of contamination were often beyond the Company's control. However, over
      the years substantial progress has been made, mainly by setting up an inspection
      system including suitable methods of analysis that allow compliance with raw
      material specifications to be checked at source. In spite of the fact that the
      problem of aflatoxins in milk, cereals, and oilseeds has now been largely
      tackled, it is increasingly necessary to step up our mycotoxin surveillance
      programme. Indeed, several other mycotoxins have now become a matter of concern,
      as witnessed by the recent fumonisin scare. Moreover, increasingly severe
      legislations put a heavy burden on the analysts responsible for the inspection of
      the raw materials, especially in European countries. This article presents the
      Company's considerable efforts over a period of almost 30 years in trying to keep
      the mycotoxins out, or at least to limit their concentrations to the lowest
      possible levels.

PMID- 7582631
TI  - Use of monoclonal antibodies for the analysis of mycotoxins.
AB  - Hybridomas producing monoclonal antibodies against aflatoxin M1, ochratoxin A,
      zearalenone, T-2 toxin, diacetoxyscirpenol, 3-acetyl-deoxynivalenol, fusarenon X,
      and roridin A were developed after immunization of BALB/c mice and fusion of the
      splenocytes with myeloma cells. The antibodies were characterized in terms of
      immunoglobulin subclass, sensitivity, and specificity. The use of these
      antibodies in competitive enzyme immunoassays, either as microtiter plate assays
      or membrane-based quick tests, as well as for the production of immunoaffinity
      columns is described. The advantages and disadvantages of monoclonal antibodies
      compared to polyclonal antisera for the improvement of mycotoxin analysis are
      discussed.

PMID- 7582635
TI  - Determination of datura alkaloids by using chromatographic techniques: a review.
AB  - A review of techniques used for the analysis of alkaloids in legume seeds,
      feedstuffs and plants is presented in this article. The analysis is performed by
      chromatographic techniques. Mainly Thin Layer Chromatography (TLC), Gas
      Chromatography (GC) and High Performance Liquid Chromatography (HPLC) are
      applied.

PMID- 7582634
TI  - Analysis of pyrrolizidine alkaloids: a competitive enzyme-linked immunoassay
      (ELISA) for the quantitative determination of some toxic pyrrolizidine alkaloids.
AB  - A highly sensitive and specific competitive enzyme-linked immunoassay (ELISA) for
      the determination of retrorsine, senecionine, and integerrimine in the nanogram
      range has been developed. Pyrrolizidine alkaloids were detected in Senecio
      rupestris. No cross-reactivity was seen with either retrosine N-oxide, otonecine
      alkaloids, or other macrocyclic pyrrolizidine alkaloids.

PMID- 7582632
TI  - Detection of fumonisins produced in Fusarium moniliforme cultures by HPLC with
      electrospray MS and evaporative light scattering detectors.
AB  - A variety of toxic secondary metabolites including fumonisins, can be produced by
      the fungus Fusarium moniliforme and closely related species in section Liseola in
      large amounts (g/kg in laboratory cultures). Underivatized fumonisins were
      detected by HPLC using either an evaporative light scattering detector or
      electrospray MS. Electrospray MS used together with NMR and GC/MS was used to
      identify a new fumonisin, fumonisin C4, which corresponds in structure to
      fumonisin B4 with the C-1 terminal methyl group missing. Several novel strains of
      F. moniliforme mating population A were identified that produced little or no
      fumonisin B1, but large amounts of either fumonisin B2, or B3 together with
      fumonisin B4 and C4. These strains which do not produce fumonisin B1 should prove
      useful in purification of fumonisin B2, B3, C4, and B4 for toxicology studies.

PMID- 7582636
TI  - CEN approach to standardisation of methods for mycotoxin analysis.

PMID- 7582637
TI  - FAO programmes for prevention, regulation, and control of mycotoxins in food.
AB  - The article provides information on recent past and current activities carried
      out by the Food and Agriculture Organization of the United Nations (FAO) at
      national, regional, and international levels to assist member countries in
      overcoming the problems raised by mycotoxins in foods and feeds. It gives special
      emphasis to the preventive aspects at the stages of production and storage of
      those commodities which are particularly sensitive to mycotoxin contamination.
      Specific projects implemented by the FAO in various countries to prevent and
      control mycotoxin contamination are cited with particular reference to the on
      going FAO/United Nations Environment Programme (UNEP) Regional Training Network
      for Mycotoxin Control in Asia. The article also provides an update of the Codex
      Alimentarius effort to establish international guideline levels for different
      mycotoxins in various foodstuffs and agricultural commodities and to develop
      sampling plans for aflatoxin control in peanuts and maize and their products. It
      proposes a set of recommended actions at various levels to monitor and control
      mycotoxin levels in foods and to promote international cooperation in this field.

PMID- 7582638
TI  - IARC activities in mycotoxin research.
AB  - The creation of the International Agency for Research on Cancer (IARC) in May
      1965 occurred only two years after publication of the chemical structure of the
      aflatoxins, and the investigation of a possible link between exposure to these
      compounds and liver cancer incidence was initiated by IARC as early as 1968.
      Thus, mycotoxins were one of the first topics of research at IARC and the
      Agency's special interest in cancer in developing countries has contributed to a
      sustained effort in this research field. The work performed comprises a number of
      aspects including laboratory research into mechanisms of action and methods for
      destruction of mycotoxins, epidemiological studies, and through evaluation of the
      carcinogenic potency of these toxins in the "IARC Monographs on the Evaluation of
      the Carcinogenic Risks to Humans." A particular feature has been the integration
      into epidemiological studies of biomarkers of mycotoxin exposure (e.g., to
      aflatoxin, ochratoxin A) developed in the IARC laboratories. The above research
      areas are described briefly below and future activities are discussed in relation
      to present knowledge and the possibilities of achieving primary prevention of
      cancer. Another field of activity in which IARC has been strongly involved is
      that of quality assurance with the organisation of the mycotoxin check sample
      programme [Friesen, 1989: J Toxicol-Toxin Reviews 8:363-373]. This activity will,
      however, not be discussed in this article in view of space limitations.

PMID- 7582639
TI  - Worldwide regulations for mycotoxins in 1994.
AB  - Since the discovery of the aflatoxins in the 1960s, regulations have been
      established in many countries to protect the consumer from harmful effects of
      mycotoxins that may contaminate foodstuffs. Various factors play a role in the
      decision-making process of setting limits for mycotoxins. These include
      scientific factors such as availability of survey data, toxicological data,
      analytical methodology, and knowledge about the distribution of mycotoxins in
      contaminated commodities. Economical and political factors such as commercial
      interests and sufficiency of food supply have their impact as well. International
      enquiries on existing mycotoxin regulation in foodstuffs and animal feedstuffs
      have been carried out several times in the 1980s and details about tolerances,
      legal bases, responsible authorities, official protocols of analysis and sampling
      have been published. The most recent enquiry is currently taking place as part of
      a contract with the Food and Agriculture Organization. At least 77 countries now
      have regulations for mycotoxins. An overview is presented of the tentative
      results of this enquiry, including frequency distributions of existing tolerances
      for aflatoxins and current trends.

PMID- 7582640
TI  - Some reflections on establishing a community legislation on mycotoxins.
AB  - A Community legislation on mycotoxins is essential to protect public health and
      to avoid trade barriers and competition distortions. Maximum permitted levels in
      food are to be fixed. Some orientations for this purpose are indicated. The
      verification of the compliance with maximum permitted levels shall need suitable
      analytical methods. Up to now, such methods were fixed by directives. This
      approach, however, had some disadvantages. A more flexible approach is to be
      planned. Among the mycotoxins to be taken into consideration, priority should be
      granted to the aflatoxins and to ochratoxin A. Fumonisins also deserve interest.
      Other mycotoxins will be taken into consideration as the need arises and
      scientific data are available. Some basic remarks on the rationale for
      establishing maximum permitted levels in food are made.

PMID- 7582642
TI  - [Epidemic of pulmonary histoplasmosis after visiting a cave in New Caledonia].
AB  - We report an epidemic of acute pulmonary histoplasmosis which occurred in
      February 1994 among a group of 24 persons after they had once or twice visited a
      cave in New Caledonia. This study describes the physical and laboratory findings,
      which lead to the diagnosis of histoplasmosis. Each test was evaluated. All
      members of the group had a physical examination, early and late serological
      tests, pulmonary X-rays (including CT) and some had mycological examination of
      bronchoalveolar washes. Mycological investigations were made on samples collected
      from the cave. Histoplasmic skin testing was not possible. We defined a case as a
      person who visited the cave in January 1994, had evocative radiological features
      and at least four symptoms among the following: weakness, fever, headache,
      arthralgia, thoracic pains, dyspnea, cough and nausea. Of the 24 exposed persons,
      7 cases were considered as severe, 8 cases as moderate, and 6 cases as mild, for
      a total of 21 cases and an attack rate of 87.5%. There was no progression towards
      disseminated histoplasmosis and no recorded death. The incubation period lasted
      from 5 to 17 days. The symptoms were divided into three groups. In the first
      group, the symptoms of fever, headache and arthralgia were common and
      nonspecific. In the second group, the symptoms of chest pain, cough, and dyspnea
      which often occurred later, were less common and more specific. In the third
      group, the symptoms of vomiting, diarrhea and dizziness were less common. The
      chest X-ray showed abnormalities in 100% of the cases, and in 11 of the 21 cases
      the characteristic finding was a miliary.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582641
TI  - [Mycetomas in Africa].
AB  - Mycetoma is the pathological process in which exogenous fungal or actinomycotic
      etiological agents generate grains. These agents belong to two groups: fungi and
      aerobic actinomycetes. Eumycetoma (caused by fungi) and actinomycetoma (caused by
      actinomycetes) must be distinguished as their treatments are different. These
      causative agents are introduced by traumas. Mycetomas are frequent in the
      northern tropical zones of America in Mexico and Venezuela, Africa in Senegal,
      Mauritania and Sudan and Asia in India, but can also be observed beyond these
      areas. In Africa, a high endemicity has been noted in a Sahelian band spanning
      from Senegal and Mauritania in the west to Somalia and the Republic of Djibouti
      in the east where there are long dry seasons and short rainy seasons. In this
      zone, M. mycetomatis (fungi) and S. somaliensis (actinomycetes) are predominant.
      A. pelletieri is common only in West Africa. Rainfall influences the distribution
      of these agents. S. somaliensis is more often found in desert areas, and A.
      pelletieri in more rainy areas. Mycetoma is more frequent in males and affects
      the age group between the second and fourth decades. Most of the patients are
      outdoor workers. In Africa, the foot is the most frequent localisation of the
      disease followed by the leg. Mycetoma is characterized by tumefaction,
      subcutaneous nodules and in most cases discharging sinuses that drain exudate
      containing grains. It gradually invades the tissues and bones causing a
      functional disability. Bone involvement depends on the duration of the disease,
      the site of the lesion and the causative agent. Invasion of lymph nodes is
      observed in rare cases, usually with actinomycetes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7582643
TI  - [African histoplasmosis due to Histoplasma capsulatum var. duboisii: relationship
      with AIDS in recent Congolese cases].
AB  - Six new cases are described for African histoplasmosis, Histoplasma capsulatum
      var. duboisii, from Congo. The first was an HIV sero-negative child who has been
      monitored for the last three years. While under treatment with ketoconazole,
      amphotericin B, and finally itraconazole, the development of the infection was
      accompanied by purulent lesions, mainly cutaneous, but also superficial and deep
      lymphadenopathies. As a last option, itraconazole gave very satisfactory results
      both during the acute phase and during long-term treatment. However, eight months
      after treatment had ceased, there was a relapse and the long-term treatment had
      to be restarted. The other cases concerned HIV sero-positive patients with
      disseminated infections that had all been mistaken for tuberculosis. After
      diagnosis of the infection in two cases, the following two years of treatment
      could not prevent death. A fourth case, diagnosed in December 1994, is currently
      undergoing treatment. The fifth subject was lost after diagnosis during follow
      up, but inquires made after the discovery of the patient's death strongly
      indicated acquired immunodeficiency as the cause. The last of these six cases,
      determined as HIV sero-negative, showed large bony lesions of the spinal column
      associated with a sore on the thorax. Thus, in a short period of time, three or
      four cases of African histoplasmosis occurred which were associated with HIV
      infection. Only seven identical observations have previously been reported in the
      literature. Therefore, we believe that this mycosis should now be included in the
      criteria for the diagnosis and definition of AIDS in the tropics.

PMID- 7582644
TI  - [Chromoblastomycosis in Gabon. Study of 64 cases].
AB  - During the last 25 years, 64 cases of chromoblastomycosis were diagnosed in
      Gabon. They came from the entire territory, where living in rural zones men as
      well as women were affected. The evolution of the disease has lasted for more
      than 10 years for the majority of the cases. The preferential location is the
      lower limb for 78.5% of the patients, with a double localization for one case and
      an exceptional malignant transformation for another case. Two clinical aspects
      emerged, despite an apparent polymorphism: extensive patches and warty nodules,
      spread apart from or adjacent to the others. The histological images were
      classical and the fumagoid cells, sometimes budding and filamentous, were easily
      detected during examination of the squama and scabs. Fonsecaea pedrosoi was the
      only identified species. The 5-fluorocytosine treatment constantly led to an
      improvement of the lesions. The major problem for these destitute patients is
      economic, concerning the cost of the therapy.

PMID- 7582645
TI  - [First case of multiforme granuloma in Congo].
AB  - We report a case of multiform granuloma observed in a young woman of 28 years
      from Brazzaville, Congo. Extended lesions on the arms, back, face, legs and feet
      appeared over one month. They consisted of slightly squamous erythemato
      oedematous plaques, with polycyclical margins and raised papular borders. The
      diagnosis was made histologically and recovery was spontaneous over a period of
      two months. We discuss clinical and histopathological aspects, which can
      sometimes lead to confusion with Hansen's disease.

PMID- 7582647
TI  - [Collective food poisoning in a camp for unaccompanied refugee children in the
      city of Goma, Zaire, September 1994].
AB  - We report a retrospective study of a group of 440 children following an outbreak
      of infectious food poisoning in Goma in 1994. The study was part of the
      epidemiological surveillance in a non-accompanied child refugee reception centre.
      There were 11 cases (rate 2.5%). We evidence a problem of hygiene in the food
      preparation chain. Despite the numerous epidemics in the region (cholera,
      dysentery) this study demonstrated that they were not responsible. Similarly, the
      findings removed any existing doubts about the quality of the food supplied as
      part of the international aid.

PMID- 7582648
TI  - [African women and AIDS: the right to know and the right to live as a
      seropositive].

PMID- 7582646
TI  - [A nutritional survey in Tibet].
AB  - We present the most striking results of a nutritional assessment held in Tibet
      from May to July 1990, performed at the request of the Health Authorities of the
      Tibet Autonomous Region. Using a cut-off value which adjusts for the haemoglobin
      increase with increasing altitude, 40% of the women of reproductive age were
      considered anaemic. However, the distribution of their haemoglobin values was
      gaussian with a mean value of 13.6%. Apparently, the Tibetans respond differently
      to high altitude, compared to other populations living at high altitudes. Goitre
      remains a problem despite the goitre control program. Rickets, investigated by
      clinical signs, was prevalent in 9.2% of the children 0 to 6 years old. Rural
      children were shorter and lighter than urban ones and started to accumulate their
      deficit earlier.

PMID- 7582649
TI  - [Leishmaniasis: new diagnostic approaches].

PMID- 7582650
TI  - Post-traumatic epilepsy and recovery of function from experimental brain damage:
      a review.

PMID- 7582654
TI  - Psychiatric morbidity and psychodynamics of patients with convulsive
      pseudoseizures.
AB  - Forty-six female patients with pseudoseizures were compared with 50 female
      patients referred to a psychiatric outpatient clinic. Patients with convulsive
      pseudoseizures were more likely to be single and childless. An abnormal EEG was
      more frequently reported in patients with convulsive pseudoseizures, contributing
      to their earlier diagnosis of epilepsy. The defence mechanisms of patients with
      convulsive pseudoseizures using the Defense Mechanisms Inventory (DMI) were
      particularly characterized by higher scores on the 'reversal' scale and lower
      scores on the 'turning against self' scale. Mood disorders were more common in
      general psychiatric patients, while one-third of convulsive pseudoseizure
      patients did not complain of psychiatric symptoms.

PMID- 7582651
TI  - Wiring, dysmorphogenesis and epilepsy: a hypothesis.
AB  - Cerebral cortical dysgenesis has been found by magnetic resonance imaging to be
      the second most common pathology underlying medically refractory chronic partial
      epilepsy. Patients with the latter condition form the largest group in specialist
      epilepsy clinics. The pathogenesis of the epilepsy in cortical dysgenesis remains
      largely obscure. The most popular current hypothesis holds neuronal misconnection
      secondary to neuronal malpositioning culpable for seizure activity. However, a
      review of the published literature of cortical dysgenesis and an analysis of
      newer magnetic resonance and histopathological data, suggests that this view is
      no longer tenable. A modified hypothesis is proposed in which neuronal
      connectivity itself is postulated to be the primary motive force in both cerebral
      morphogenesis and epileptogenesis in cases of cortical dysgenesis. This
      hypothesis leads to the generation of a model for cortical development and
      directly testable predictions of intercellular connectivity, as well as a
      potential tool for the prediction of the possibility of freedom from seizure
      activity after surgical resection of dysgenetic lesions in individual cases.

PMID- 7582652
TI  - Design of clinical antiepileptic drug trials.
AB  - It may fairly be claimed that up to the last decade no antiepileptic drug (AED)
      had undergone rigorous testing. The development programmes of the new AEDs
      registered in recent years have necessarily been innovative, and methods of AED
      testing are still undergoing rapid evolutionary change. Clinical evaluation of
      AEDs is both difficult and complex, due mainly to two factors: (1) intermittence
      of clinical events, which means that dosing for periods of several weeks is
      generally necessary, leading to problems of poor compliance and inaccurate
      reporting of events by carers and patients; and (2) therapeutic necessity, which
      means that it is, in general, unacceptable to withhold effective treatment from a
      person with epilepsy. Consequently monotherapy, either with a trial drug or with
      placebo, can rarely be justified. In consequence most phase II trials use add-on
      therapy which in turn causes various problems. Conventional phase II AED trials
      are usually placebo-controlled add-on studies employing either a parallel or
      crossover design. The latter is subject to a number of practical and theoretical
      objections, notably on grounds of carry-over and order effects. Increasing
      attention has recently been directed to ethically acceptable monotherapy designs.
      One approach first exploited in the development of felbamate is the performance
      of monotherapy trials in patients whose AEDs have been withdrawn as part of a
      preoperative assessment protocol. Other possibilities for achieving monotherapy
      are also discussed.

PMID- 7582656
TI  - Rational polypharmacy.
AB  - The development of assays for plasma antiepileptic drug concentrations has led to
      the discovery of many pharmacokinetic interactions, some causing drug
      intoxication and others resulting in ineffective drug concentrations. In the
      1970s, a number of epileptologists began to argue that single drug therapy was
      desirable in the treatment of epilepsy and this has become the accepted policy
      when initiating therapy. About 75% of patients treated in this way will achieve
      remission with a minimum of adverse drug reactions. The remainder, however,
      continue to have unacceptable seizures and usually receive combinations of drugs.
      Evidence indicates that the response rate on adding a second drug is low,
      although in some studies of new drugs such as vigabatrin up to one-half of
      patients receiving add-on therapy experience a 50% or greater reduction in
      seizure frequency, and 10-15% are seizure-free in the short term. Unfortunately,
      randomized placebo-controlled studies have not been undertaken to compare the
      relative merits of monotherapy and combination therapy with respect of seizure
      control and adverse effects. It is argued that the time has come to do so,
      particularly in view of the known mode of action of some of the new drugs.
      Perhaps blocking excitation with one drug at the same time as enhancing
      inhibition with another may be better than doing only one or the other.

PMID- 7582655
TI  - What resources? Addressing the needs of the epilepsy community.
AB  - Epilepsy is a condition which spans several disciplines within medicine, as well
      as having an impact on many non-medical areas such as employment and education.
      Services for epilepsy in the UK have not been developed according to any coherent
      strategy and remain fragmented and unevenly distributed. Successive attempts to
      address these shortcomings by publishing recommendations, even with government
      assistance, have not led to major improvements. Recent changes in the
      organization of health care services might at least present an opportunity to
      effect change by educational initiatives directed towards purchasers and
      providers. However, the absence of epilepsy from The Health of the Nation
      objectives represents a failure to get the message through to those with the
      ability to direct policy. The plethora of new, effective and expensive
      pharmaceutical treatments should lead to a raising of epilepsy awareness among
      the medical profession as a consequence of marketing activity, but this is
      already causing conflict with Family Health Service Associations (FHSAs) and
      others with equivalent lack of vision. I would suggest that only by politicizing
      the consumer can the change we seek be brought about.

PMID- 7582653
TI  - Epilepsy and employment--employers' attitudes.
AB  - The aim of this study was to examine the possible causes of employment
      difficulties amongst people with epilepsy by interviewing employers. It was hoped
      that the outcome of the study would complement the research already carried out
      in this field by concentrating on the attitudes and policies of employers. Due to
      the time limit it was decided that a small number (five) of local employers
      should be approached requesting an interview. The employers were randomly
      selected but were all large companies within varying industries. All employers
      approached agreed to participate in the study and interviews were arranged with
      welfare recruitment staff. The interviews were limited to 45 minutes and
      concentrated on three main issues for discussion: disclosure, unemployment and
      improved relationship between employers and people with epilepsy. The outcome of
      the interviews was that the employers appeared to be rather unaware of the
      employment problems faced by people with epilepsy. As epilepsy is generally not a
      registered disability employers are unable to monitor their company's recruitment
      and promotion methods. It seems that line managers are left to decide on the
      employment of people with epilepsy often without even general awareness training
      on equal opportunities. Consequently their need to meet targets and their
      personal attitude to epilepsy determine the employment chances for people with
      epilepsy. Only with legislations protecting the interests of people with epilepsy
      can the unemployment figures be brought in line with the general population.

PMID- 7582658
TI  - Development of a scale to measure core beliefs and perceived self efficacy in
      adults with epilepsy.
AB  - A scale based on underlying core beliefs generated by the experience of epilepsy
      was developed. The scale, with measures of coping, adaptability, and knowledge,
      was used to examine the commonly-reported differences in emotional adjustment
      between patients (EP) and a non-epileptic population (NEP). The EP had
      significantly lower perceived self efficacy and was more depressed and anxious
      than the NEP controls. The NEP showed greater knowledge of medical aspects of
      epilepsy than the EP. Positive correlations between scale values and measures of
      mastery, self esteem, affect balance, felt stigma and impact of epilepsy were
      found. Factor analysis produced a three factor solution of emotion, knowledge and
      anxiety which explained 61.6% of the variance in scores. Results are discussed in
      terms of Bandura's theory of self efficacy as the motivating and sustaining force
      in the ability to change behaviour. Core beliefs are central to both the
      development and maintenance of anxiety and depression in epilepsy patients and
      need to be addressed in any attempts at remedial intervention.

PMID- 7582657
TI  - Management issues in severe childhood epilepsies.
AB  - The severe epilepsies of childhood are described briefly and information
      available on the efficacy of newly developed antiepileptic drugs (AEDs) in their
      control is reviewed. Therapeutic advances are awaited for early infantile
      epileptic encephalopathy, early myoclonic encephalopathy, progressive myoclonus
      epilepsies and Kojewnikow syndrome. West syndrome may respond to vigabatrin, and
      less predictably to lamotrigine. Lamotrigine can be helpful for severe myoclonic
      epilepsy and myoclonic absences. Astatic seizures may be dramatically controlled
      by lamotrigine, whereas vigabatrin may worsen myoclonic attacks. In the Lennox
      Gastaut syndrome, the efficacy of felbamate has been demonstrated by a controlled
      trial; vigabatrin and lamotrigine can also be helpful. Non-idiopathic partial and
      secondary generalized epilepsies are responsive to vigabatrin in a useful
      percentage of cases, and some children improve with felbamate, lamotrigine or
      striripentol. A trial which compares the efficacies of the newer AEDs against
      each other could provide very useful information for the clinician.

PMID- 7582659
TI  - The efficacy of lamotrigine on seizure control in 34 children, adolescents and
      young adults with intellectual and physical disability.
AB  - This study reports the use of lamotrigine, largely as add-on therapy, in 34
      children, adolescents and adults with brain damage and resistant seizures.
      Seventy-four percent of the patients showed a greater than 50% improvement in
      seizure control with 35% becoming seizure free. This improvement in seizure
      control was associated with an enhanced quality of life in 65% of the patients as
      assessed by improved alertness, mobility, speech and independence. It was
      possible to reduce 36% of the pre-existing antiepileptic drugs and the side
      effect profile of lamotrigine was very good. It is proposed that lamotrigine may
      be a particularly useful antiepileptic drug in this particular group of patients.

PMID- 7582661
TI  - Supplementary motor area seizures presenting as stumbling episodes.
AB  - A healthy young boy presented with brief stumbling episodes of recent onset.
      Evaluation with prolonged EEG-video monitoring led to the diagnosis of
      supplementary motor area epilepsy. Focal seizures arising from the medial fronto
      parietal cortex may present unusual diagnostic pitfalls in their clinical
      semeiology as well as their EEG characteristics.

PMID- 7582660
TI  - Bradycardia, an epileptic ictal manifestation.
AB  - Two patients with recurrent paroxysmal cardio-vascular symptoms are described.
      The first, an adult, suffered from syncopal events which did not respond to
      carbamazepine treatment and had a normal interictal EEG and ECG. The second, a
      child, presented with attacks of cyanosis, apnoea, and non-responsiveness in
      clusters, with normal interictal examinations. In both patients, prolonged
      simultaneous EEG and ECG monitoring demonstrated ictal bradycardia accompanied by
      paroxysmal discharges in the left temporal area.

PMID- 7582662
TI  - Ictal verbal behaviour.

PMID- 7582664
TI  - Lone mothers and their children.

PMID- 7582663
TI  - Cognitive neuropsychiatry and the future of diagnosis: a 'PC' model of the mind.

PMID- 7582665
TI  - Psychological and sexual symptoms associated with the menopause and the effects
      of hormone replacement therapy.
AB  - BACKGROUND: There is considerable inconsistency in the results of studies of the
      psychological and sexual sequelae of the menopause and their treatment. METHOD: A
      search of the literature on Medline was made of studies of psychological symptoms
      in women who were either naturally or surgically menopausal or who were receiving
      hormone replacement therapy for menopausal symptoms. RESULTS: There is evidence
      of a small increase in psychological morbidity (not usually amounting to
      psychiatric disorder) preceding the natural menopause and following the surgical
      menopause. Psychosocial as well as hormonal factors are relevant. While the
      response of psychosocial symptoms to hormone replacement therapy with oestrogens
      is variable and most marked in the surgical menopause, in some studies the effect
      is little greater than that for placebo. Where sexual symptoms are present, there
      is more consistent evidence that hormone replacement therapy is effective.
      CONCLUSIONS: In the light of the available evidence, the current use of hormone
      replacement therapy to treat psychological symptoms detected at the time of (but
      not necessarily therefore due to) the natural menopause must be questioned. It
      does appear that oestrogen therapy ameliorates psychological symptoms after
      surgical menopause.

PMID- 7582666
TI  - Two faces of Emil Kraepelin.

PMID- 7582667
TI  - Gender and schizophrenia. Results of an epidemiologically-based family study.
AB  - BACKGROUND: Gender may have a significant impact on the prevalence, age at onset,
      symptoms, course and outcome of schizophrenia, as well as on the pattern of
      psychopathology in relatives. METHOD: We examined these questions in the
      Roscommon Family Study, in which the probands were epidemiologically sampled from
      a case registry and followed up an average of 15 years after onset. Face-to-face
      interviews were conducted with 86% of traceable living relatives. RESULTS: The
      treated lifetime prevalence of DSM-III-R schizophrenia was 0.54 +/- 0.06% in men
      and 0.28 +/- 0.04% in women. No significant differences were seen in the age at
      onset, symptoms, course or outcome of schizophrenia. The risks for schizophrenia,
      schizophrenia spectrum disorders, affective illness and alcoholism were similar
      in relatives of male and female schizophrenic probands. CONCLUSIONS: Gender has
      little impact on the presentation and course of schizophrenia in the west of
      Ireland. The familial liability to schizophrenia did not differ in affected men
      and women. No evidence was found that schizophrenia in women, compared to men,
      is, from a symptomatic or familial perspective, more closely related to affective
      illness. The substantial gender difference in the prevalence rate of
      schizophrenia in Ireland cannot be explained by women having a greater resistance
      to the familial predisposition to illness.

PMID- 7582669
TI  - Sensorimotor cortex and supplementary motor area changes in schizophrenia. A
      study with functional magnetic resonance imaging.
AB  - BACKGROUND: Neurological soft signs (NSS) such as a disturbed finger-to-thumb
      opposition are frequently found in schizophrenia. To identify the underlying
      cerebral changes we investigated sensorimotor cortex and supplementary motor area
      (SMA) activation during finger-to-thumb opposition using functional magnetic
      resonance imaging (fMRI). METHOD: Ten DSM-III-R schizophrenics and seven healthy
      controls were included. All subjects were right-handed. fMRI was carried out in a
      resting condition followed by an activation state (finger-to-thumb opposition)
      and the activities in the sensorimotor cortices and SMA recorded. RESULTS: All
      subjects showed a significant activation of the SMA and both ipsilateral and
      contralateral sensorimotor cortices. In the controls, ipsilateral finger-to-thumb
      opposition was associated with a greater left than right hemispheric sensorimotor
      cortex coactivation. When compared with the healthy controls, the schizophrenic
      patients showed a decreased activation of both sensorimotor cortices and SMA, as
      well as a reversed lateralisation effect. CONCLUSION: Sensorimotor cortex and SMA
      dysfunction are associated with motor disturbances in schizophrenia.

PMID- 7582668
TI  - The incidence of first contact schizophrenia in Jamaica.
AB  - BACKGROUND: Afro-Caribbean immigrants are reported to have a high rate of
      schizophrenia compared with other population groups. METHOD: In a prospective
      first contact study of schizophrenia in Jamaica in 1992, 335 patients were
      examined using the Present State Examination. RESULTS: 285 patients were
      evaluated as having a PSE 'restrictive' S+ diagnosis of schizophrenia, and 32 as
      having a 'broad' S?, P, or O diagnosis of schizophrenia. With a population of
      2.46 million, this represents a first-contact incidence rate for 'restrictive'
      schizophrenia of 1.16 per 10,000 population, and an age-corrected (15-54)
      incidence rate of 2.09 per 10,000. CONCLUSION: Incidence rates for schizophrenia
      in Jamaica are lower than those reported in Afro-Caribbean immigrants in the UK
      and Holland, and within the reported range for other population groups worldwide.

PMID- 7582670
TI  - Magnetic resonance imaging and single photon emission tomography in treatment
      responsive and treatment-resistant schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia differ from controls in several measures
      of brain structure and function, but it is uncertain how these relate to clinical
      features of the illness. We dichotomised patient groups by treatment response to
      test the hypothesis that treatment-resistant patients exhibit more marked
      biological abnormalities than treatment-responsive patients. METHOD: Twenty
      treatment-responsive and 20 treatment-resistant patients with schizophrenia,
      matched for sex, age, and illness duration, were compared by magnetic resonance
      imaging, single photon emission tomography, and detailed neuropsychological
      assessment. RESULTS: Brain-imaging variables were not statistically related to
      treatment response, although poorly responsive patients had lower volumes of most
      brain structures. Several highly significant differences emerged between patient
      groups on neuropsychological testing. Episodic memory functioning distinguished
      patient groups even after we controlled for global cognitive impairment.
      CONCLUSIONS: Cerebral structure and blood flow have a limited effect on treatment
      response in schizophrenia, but long-term episodic memory impairment is associated
      with, and may predict, poor prognosis.

PMID- 7582671
TI  - Relationship between movement planning and psychopathology profiles in
      schizophrenia.
AB  - BACKGROUND: There has been evidence that psychopathology in schizophrenia
      consists of three separable syndromes: reality distortion, disorganisation, and
      psychomotor poverty. The objective of this study was to explore the relationship
      between planning and execution of movement and each of the syndromes in
      schizophrenia. METHOD: Twenty-one right handed DSM-III-R schizophrenic patients
      performed a total of 80 trials of a motor movement task, varying distance of
      movement x size of the target x hand. Times taken to plan the movement (RT) and
      to carry it out (MT) were examined for their relationship with contemporaneous as
      well as lifetime profiles of the three syndromes in schizophrenia. RESULTS:
      Significant correlations are reported between RT and current as well as lifetime
      measures of disorganisation syndrome. Somewhat weaker correlations are reported
      between RT and psychomotor poverty, but only for the right-handed tasks. Partial
      correlations suggest that the influence of neuroleptic medication explains all
      but one of the correlations between psychomotor poverty and RT, but does not
      account for the relationship between disorganisation and RT. No other
      relationship emerged between any of the movement and symptom measures.
      CONCLUSIONS: These findings indicate that dysfunction in movement planning is
      related primarily to concurrent disorganisation, as well as to the prominence of
      disorganisation over the patient's history.

PMID- 7582672
TI  - Delineation of acute and transient psychotic disorders in a developing country
      setting.
AB  - BACKGROUND: We examined whether acute transient psychoses can be distinguished
      from schizophrenia and the affective disorders. METHOD: We studied 46 cases of
      nonaffective acute psychosis in the Chandigarh Acute Psychosis Study. With
      respect to separation from schizophrenia, we examined the distribution of
      duration of the episode. With respect to separation from affective disorders, we
      assessed the frequency of affective symptoms. RESULTS: Duration was bimodal,
      suggesting the presence of two distinct conditions of short and long duration.
      Affective symptoms were minimal, suggesting that these were not atypical
      affective syndromes. CONCLUSIONS: Acute transient psychoses conform neither with
      schizophrenia of brief duration nor with atypical affective psychosis, and thus
      require separate classification as proposed in the ICD-10.

PMID- 7582673
TI  - Episodes of care for first-ever psychiatric patients. A long-term case-register
      evaluation in a mainly urban area.
AB  - BACKGROUND: Psychiatric case registers (PCRs) are particularly useful for
      studying patterns of care over time. Methods of 'survival analysis' have rarely
      been used for assessing such data. METHOD: A longitudinal study was conducted
      over 10 years (1 January 1982 to 31 December 1991) on 1423 first-ever psychiatric
      patients, using the PCR of South Verona, Italy. The product-limit method, the log
      rank test, the Cox regression model and the Poisson regression analysis were used
      to analyse episodes of care and relapses. RESULTS: The duration of the episodes
      of care increased consistently from the first to the fifth episode. The
      probability of opening a new episode of care after the first one increased
      consistently from the second to the sixth episode. The only variable
      significantly associated with the length of the first episode of care was
      diagnosis (highest probability of having longer episodes for schizophrenic
      patients), while the length of the breaks following the first episode of care was
      associated with diagnosis, sex and occupational status (highest probability of
      opening a second episode of care for schizophrenic subjects and those with
      alcohol and personality disorders, for males, and for unemployed patients). The
      probability of opening a new episode of care decreased with time since last
      contact and increased with number of previous contacts. CONCLUSIONS: The
      community psychiatric service in South Verona is fulfilling its original aim,
      that is, to give priority to the continuity of care for patients with chronic and
      severe mental illnesses. Survival analyses proved to be useful methods for
      assessing episodes of care.

PMID- 7582674
TI  - Medium-term course of disaster victims. A naturalistic follow-up.
AB  - BACKGROUND: Our aim was to describe the medium-term course (2-3 years) in a
      series of victims who had experienced severe trauma. METHOD: We selected a
      consecutive series of 31 trauma victims and applied a structured clinical
      schedule (CAPS-2) to their psychiatric evaluations prepared for the court on two
      separate occasions approximately one year apart. RESULTS: Post-traumatic stress
      disorder and depression were the commonest diagnoses, occurring in 39% and 16% of
      the victims respectively when they were first assessed. Most had improved between
      the assessments and this was especially the case for the re-experiencing of the
      trauma and over-arousal, but less so for avoidance; 20% of subjects showed no
      improvement, often being handicapped by secondary psychiatric illness.
      CONCLUSION: Traumatised victims generally showed recovery in the 2-3 years after
      the trauma, but this was slow and was not universal.

PMID- 7582675
TI  - The psychological effects of disaster at sea.
AB  - BACKGROUND: In March 1987, the P&O car ferry Herald of Free Enterprise capsized
      killing 193 passengers. Seventy-five survivors and relatives were referred by
      their solicitors to the authors for assessment of psychological injury. METHOD:
      Information was gathered retrospectively and systematically from clinical notes
      and legal reports. RESULTS: The commonest symptoms suffered were sleep
      disturbance, loss of concentration and increased anger. The commonest diagnoses
      were post-traumatic stress disorder, other anxiety states and depression.
      Depressive symptoms were commoner in those who had been bereaved, anxiety
      symptoms were commoner in those who had not. Reluctance to discuss symptoms and
      to attend a psychiatric clinic was a common feature. CONCLUSIONS: As expected,
      bereavement led to grief and depressive symptoms, whilst passengers who were not
      bereaved were more likely to suffer anxiety symptoms. Contrary to expectations,
      the degree of immersion during the accident did not influence the type or degree
      of symptoms. Those with worse symptoms were more likely to attend the clinic.
      Women showed more affective symptoms and men more substance abuse.

PMID- 7582678
TI  - Brain perfusion abnormalities in Gilles de la Tourette's syndrome.
AB  - BACKGROUND: Functional brain imaging with technetium-99m d,l-hexamethyl
      propyleneamine oxime (HMPAO) Single Photon Emission Tomography (SPET) allows us
      to explore the cerebral pathophysiology of Gilles de la Tourette's Syndrome
      (GTS). METHOD: Fifty patients and 20 controls were examined. Patients were rated
      for tic severity and mood. Scans were analysed quantitatively using internal
      ratios to the occipital cortex. RESULTS: Patients different from controls on
      measures of relative blood flow to the left caudate, anterior cingulate cortex
      and the left dorsolateral prefrontal cortex. Severity of tics was related to
      hypoperfusion of the left caudate and cingulate and a left medial temporal
      region. Hypoperfusion in the left dorsolateral prefrontal region was related to
      mood. CONCLUSIONS: The areas found to be hypoperfused in this study are
      consistent with known functions of fronto-striatal circuits. A wide range of
      perfusion patterns is seen, however, and no characteristic patterns for
      behavioural subgroups has been documented with this technique.

PMID- 7582677
TI  - Termination of pregnancy and psychiatric morbidity.
AB  - BACKGROUND: We investigated whether reported psychiatric morbidity was increased
      after termination of pregnancy compared with other outcomes of an unplanned
      pregnancy. METHOD: This was a prospective cohort study of 13,261 women with an
      unplanned pregnancy. Psychiatric morbidity reported by GPs after the conclusion
      of the pregnancy was compared in four groups: women who had a termination of
      pregnancy (6410), women who did not request a termination (6151), women who were
      refused a termination (379), and women who changed their minds before the
      termination was performed (321). RESULTS: Rates of total reported psychiatric
      disorder were no higher after termination of pregnancy than after childbirth.
      Women with a previous history of psychiatric illness were most at risk of
      disorder after the end of their pregnancy, whatever its outcome. Women without a
      previous history of psychosis had an apparently lower risk of psychosis after
      termination than postpartum (relative risk RR = 0.4, 95% confidence interval CI =
      0.3-0.7), but rates of psychosis leading to hospital admission were similar. In
      women with no previous history of psychiatric illness, deliberate self-harm (DSH)
      was more common in those who had a termination (RR 1.7, 95% CI 1.1-2.6), or who
      were refused a termination (RR 2.9, 95% CI 1.3-6.3). CONCLUSIONS: The findings on
      DSH are probably explicable by confounding variables, such as adverse social
      factors, associated both with the request for termination and with subsequent
      self-harm. No overall increase in reported psychiatric morbidity was found.

PMID- 7582679
TI  - Incidence of clinically diagnosed subtypes of dementia in an elderly population.
      Cambridge Project for Later Life.
AB  - BACKGROUND: In developed countries, most dementia appears to be due to
      Alzheimer's disease and vascular dementia. We report rates for incidence of
      subtypes of dementia based on clinical diagnosis. METHOD: This study was a 2.4
      year (s.d. 2.6 months) follow-up of a cohort aged 75 years and over, seen
      initially in a prevalence study of dementia. A screening interview in 1173
      survivors was followed in a subsample of 461 respondents by a diagnostic
      interview 1.8 months after screening (s.d. 1.5 months). This comprised a
      standardised interview with respondent and informant, with venepuncture where
      possible. Clinical diagnoses of subtypes were made by specified criteria.
      RESULTS: The incidence of Alzheimer's disease of mild and greater severity was
      2.7/1000 person-years at risk (1.6-4.4); in men 1.5 (0.8-2.7) and in women 3.3
      (1.8-5.9). The incidence of vascular dementia was 1.2/100 person-years at risk
      (0.7-1.9); in men 1.1 (0.4-2.8) and in women 1.2 (0.7-2.0). Alzheimer's disease,
      but not vascular dementia, showed a marked increase with age, particularly in
      women. Rates for minimal dementia of different subtypes showed similar age and
      sex effects, but were much higher for Alzheimer's disease than vascular dementia.
      CONCLUSIONS: The striking rise in incidence rates of dementia in the very old
      appear to be due to Alzheimer's disease, while rates for vascular dementia remain
      relatively constant. These trends are particularly marked for minimal dementia,
      but emphasise the importance of Alzheimer's disease in the community as a cause
      of cognitive decline of all degrees.

PMID- 7582676
TI  - Effect of valine on 5-HT-mediated prolactin release in healthy volunteers, and on
      mood in remitted depressed patients.
AB  - BACKGROUND: Animal experimental studies suggest that the amino acid valine may
      decrease brain serotonin (5-HT) function by inhibiting the transport of the 5-HT
      precursor, L-tryptophan, across the blood barrier. The aim of the present study
      was to assess whether valine could decrease brain 5-HT function in healthy
      subjects and provoke symptomatic relapse in recently remitted depressed patients
      taking antidepressant drug treatment. METHOD: We studied the effect of valine (30
      g) on the prolactin (PRL) response to the 5-HT releasing agent, D-fenfluramine,
      in healthy male subjects and on the mood of 12 remitted depressed patients taking
      either selective serotonin re-uptake inhibitors (n = 10) or lithium and
      amitriptyline (n = 2). RESULTS: Valine significantly lowered the PRL response to
      D-fenfluramine in healthy subjects. In the remitted depressives, valine caused a
      mild but detectable lowering of mood on a number of measures but only one patient
      experienced a significant relapse in mood. CONCLUSIONS: Valine administration may
      decrease brain 5-HT neurotransmission in humans. This effect could explain the
      mild increase in depressive symptoms in patients taking 5-HT-potentiating drugs.

PMID- 7582680
TI  - Multiple personality disorder and false memory syndrome.

PMID- 7582681
TI  - Multiple personality disorder and false memory syndrome.

PMID- 7582682
TI  - Multiple personality disorder and false memory syndrome.

PMID- 7582683
TI  - Publication bias and meta-analysis.

PMID- 7582684
TI  - Women's response to adversity.

PMID- 7582685
TI  - Structured abstracts.

PMID- 7582686
TI  - Psychosocial outcome of liver transplant.

PMID- 7582687
TI  - Costs of community psychiatric nurse teams.

PMID- 7582690
TI  - Studies of sleep in fibromyalgia; techniques, clinical significance, and future
      directions.

PMID- 7582688
TI  - Intramuscular injections in the anticoagulated state.

PMID- 7582689
TI  - Statistical design, analysis and further correspondence.

PMID- 7582691
TI  - Conceptualizing and defining outcome.

PMID- 7582692
TI  - Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with
      systemic lupus erythematosus and primary Sjogren's syndrome.
AB  - To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers
      of affected children were HLA typed for class I and II antigens, and the results
      were compared with the corresponding HLA types in 900 healthy controls, in 45
      mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS
      who had healthy children. An enzyme-linked immunosorbent assay was used to study
      the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa
      SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens.
      Mothers of children with CHB had HLA B8 and DR3 significantly more often than
      healthy controls [71 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%;
      RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029).
      Compared to controls with SLE, mothers of children with CHB were more often HLA
      DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively),
      and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P =
      0.010). In general, the HLA antigen profile in mothers of children with CHB was
      more closely related to primary SS than to SLE. Levels of antibodies to all three
      SS-A/Ro antigens were significantly higher in mothers of children with CHB than
      in controls with SLE and primary SS (P = 0.0001-0.0014). With regard to SS-B/La,
      the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7582693
TI  - Detection of antiribosomal P protein antibodies in patients with systemic
      sclerosis.
AB  - This study investigated the prevalence and clinical significance of anti
      ribosomal P protein (anti-P) antibodies in patients with systemic sclerosis
      (SSc). Serum samples from 150 patients with SSc were examined by indirect
      immunofluorescence. ELISA and immunoblotting. Anti-P antibodies were detected in
      four (3%) patients with SSc. Three of the four patients showed SSc/SLE (systemic
      lupus erythematosus) overlap syndrome, but psychiatric disorders were not
      observed in these patients. By longitudinal immunoblotting analysis one patient,
      who was initially diagnosed with SSc, later developed anti-P antibodies along
      clinical manifestations of SLE. Our data suggest that anti-P antibodies are
      uncommon in SSc and that the presence of anti-P antibodies in patients with SSc
      indicates an overlap with SLE.

PMID- 7582694
TI  - The antiperinuclear factor in spondylarthropathies.
AB  - The aim of the present study was to evaluate the prevalence of antiperinuclear
      factor (APF) in patients with spondylarthropathy and the relationships between
      this autoantibody and a variety of clinical, radiological and serological
      findings. We conducted a retrospective review of the medical records of all
      patients first admitted to the Rheumatology Unit of the Brest University Medical
      School Hospital from 1 January 1986 to 31 December 1994, and who met the European
      Spondylarthropathy Study Group (ESSG) criteria at admission. Each patient had a
      standard battery of tests. Serum samples from 123 of 126 patients suffering from
      spondylarthropathy were examined for the presence of APF. Thirty-three patients
      (26.8%) had APF at a titre > or = 1/80. There were no significant relationships
      between various demographic, clinical or radiological characteristics and the
      presence of APF. However, the subgroup of APF-positive patients had a higher
      prevalence of both rheumatoid factors (RF), although not significant, and
      antikeratin antibody-positive serum than the rest. These results suggest that
      some patients had rheumatoid arthritis (RA) and three patients with APF > 1/100
      and who were RF positive met ACR criteria for RA. APF should thus be used only as
      an additional serological marker in cases where clinical features suggest the
      association of spondylarthropathy with RA.

PMID- 7582695
TI  - Changing autoantibody profiles with variable clinical manifestations in a patient
      with relapsing systemic lupus erythematosus and polymyositis.
AB  - The production of autoantibodies characteristic of different autoimmune disease
      subsets is thought to be controlled primarily by genetic factors, whereas non
      genetic factors are generally believed to be of secondary importance. A patient
      with systemic lupus erythematosus (SLE) and polymyositis (PM) who experienced
      frequent relapses associated with changing clinical manifestations and
      autoantibody specificities is reported. Her initial presentation as SLE with anti
      Sm antibodies shifted to the onset of PM with temporal production of a different
      set of autoantibodies. The latter antibodies disappeared when myositis resolved,
      followed by the reappearance of autoantibodies and clinical manifestations
      characteristic of SLE. The shifts of autoantibody profiles in association with
      variable clinical manifestations in this patient argue that environmental factors
      may play a more important role in autoimmunity than previously supposed, and that
      interplay between environmental triggers and genetic predisposing factors may
      lead to the constellation of autoimmune disease manifestations exhibited at a
      particular time.

PMID- 7582696
TI  - Increased VLDL levels and diminished renal excretion of uric acid in
      hyperuricaemic-hypertriglyceridaemic patients.
AB  - The objective was to study the lipoprotein levels in primary hyperuricaemic
      patients and to analyse their renal management or urates in order to check for
      some potential influence of altered lipid levels on the renal excretion of urates
      by this type of patient. Overall 115 male individuals were studied in five
      groups, namely: 30 primary hyperuricaemic (group I); 27 primary hyperuricaemic
      hypercholesterolaemic (group II); nine primary hyperuricaemic
      hypertriglyceridaemic (group III); 33 primary hyperuricaemic-mixed
      hyperlipidaemic (group IV); and 16 normouricaemic-normolipidaemic subjects (group
      C). All patients were subjected to blood analyses for uric acid, total
      triglycerides, total protein, creatinine, high density lipoprotein (HDL)
      cholesterol, very low density lipoprotein (VLDL) cholesterol, low density
      lipoprotein (LDL) cholesterol, apoprotein (apo) AI, apoprotein B, apoprotein CII
      and apoproteins CIII1 and CIII2. For urine analysis creatinine, creatinine
      clearance, uric acid excretion, clearance and fractional excretion were measured
      in 24 h urine samples. Mixed and pure hyperuricaemic-hypertriglyceridaemic
      patients exhibited increased levels of VLDL components, decreased fractional
      excretion of uric acid and increased apo CIII/CII ratios. The increased levels of
      structural VLDL components were negatively (and statistically significantly)
      correlated with the fractional excretion of uric acid; this suggests a close
      biological relationship between the two parameters. Taking into account the role
      played by apo C in VLDL metabolism, the altered apo CIII/CII ratios found in
      hyperuricaemic-hypertriglyceridaemic patients (both pure and mixed) suggest that
      this apoprotein plays a central role in the physiopathology of the alterations
      observed.

PMID- 7582697
TI  - Muscle strength, voluntary activation and cross-sectional muscle area in patients
      with fibromyalgia.
AB  - The objectives were to determine whether the low muscle strength in fibromyalgia
      is due to lack of exertion and to determine the relation between strength and
      muscle area. Secondarily we examined the voluntary muscle strength of the
      different muscles of the leg. The twitch interpolation technique was used to
      estimate the degree of central activation and the 'true' quadriceps muscle
      strength. Muscle cross-sectional area was determined with magnetic resonance
      imaging (MRI). The estimated 'true' muscle strength was 91 Nm (S.D. = 34 Nm) in
      15 fibromyalgia patients compared with 125 Nm (28 Nm) in 14 healthy controls (P <
      0.02). The 'true' strength divided by the sum of the maximal areas of the four
      bellies of the quadriceps muscle was lower, being 1.56 Nm/cm2 (0.32 Nm/cm2) in
      fibromyalgia patients compared with 2.11 Nm/cm2 (0.39 Nm/cm2) in the controls (P
      < 0.001). The voluntary muscle strength of the flexor muscles of the knee and of
      the plantar flexors of the ankle was markedly reduced in patients, but no
      significant differences could be observed in the strength of the dorsal flexors
      of the ankle. In conclusion, a reduction of the estimated 'true' quadriceps
      muscle strength per unit area of about 35% was found in fibromyalgia patients.

PMID- 7582698
TI  - Sensitivity and specificity of different diagnostic criteria for Behcet's disease
      according to the latent class approach.
AB  - In this study, we estimated the sensitivity and specificity of different criteria
      (International, Japanese, Mason & Barnes, O'Duffy, James and clinical judgement)
      for Behcet's Disease using the latent class approach. Thirty-two consecutive
      Behcet's Disease patients who were initially diagnosed according to clinical
      judgement, and 56 control patients with other rheumatic diseases, were recruited
      from the rheumatology out-patient clinic. The patients had their charts reviewed,
      were interviewed and clinically examined. Various models including different
      combinations of the six diagnostic criteria were tested. In the model that
      included all the information gathered, the International (sensitivity = 0.95,
      specificity = 1.00), Japanese (sensitivity = 1.00, specificity - 0.95) and Mason
      & Barnes criteria (sensitivity = 1.00, specificity = 0.94) were the most
      accurate. Clinician judgement also performed very well in identifying a Behcet's
      Disease case (sensitivity = 1.00, specificity = 0.85). The International,
      Japanese and Mason & Barnes criteria were the most accurate. The latent class
      method led to these conclusions without making any initial assumptions about the
      accuracy of any of the competing criteria (including clinical judgement).

PMID- 7582699
TI  - Aetiology and presenting symptoms in male osteoporosis.
AB  - In order to analyse the clinical characteristics and the principal causes of
      osteoporosis in men, 81 osteoporotic males from an out-patient rheumatology
      department were studied. Bone mass assessment, automated biochemical profile and
      biochemical markers of bone turnover were performed in all patients, and hormonal
      measurements were taken when a specific aetiology was not readily apparent. Sixty
      three men (78%) had secondary osteoporosis and 18 (22%) primary osteoporosis.
      Secondary causes of osteoporosis included hypogonadism (12 patients),
      corticosteroid therapy (10 patients) and alcoholism (10 patients); the remaining
      patients had various causes of osteoporosis. Eighteen patients had primary
      osteoporosis, eight of them with associated hypercalciuria. Normocalciuric
      patients showed lower 25-hydroxyvitamin D and 1-25-hydroxyvitamin D levels than
      the control group, whereas hypercalciuric patients had lower parathyroid hormone
      and renal threshold for phosphate excretion. In 69 patients (85%), back pain was
      the chief complaint. Forty-five of these 69 patients (65%) had chronic back pain
      and 24 (35%) had subacute episodes. Fifty per cent of the patients with chronic
      back pain had vertebral fractures. Both patients with and without chronic back
      pain were found to have a similar number of vertebral fractures. In conclusion,
      male osteoporosis is frequently associated with major risk factors. Patients with
      primary osteoporosis may have associated hypercalciuria or decreased vitamin D
      levels. However, not all the patients for whom back pain was the chief complaint
      were found to have vertebral fractures.

PMID- 7582700
TI  - Cutaneous leucocytoclastic vasculitis: a clinical and aetiological study.
AB  - Cutaneous vasculitis may be the presenting sign in many different clinical
      disorders. The aetiology and clinical and laboratory findings were recorded in 69
      consecutive patients with cutaneous leucocytoclastic vasculitis. Underlying
      connective tissue disease or malignancy was found in 19 patients. Evidence of
      recent streptococcal infection was detected in 24 patients. Application of the
      classification criteria proposed by the American College of Rheumatology (ACR)
      identified 35 patients with Henoch-Schonlein purpura (HSP) and 42 with
      hypersensitivity vasculitis (HSV). Thirty-three subjects fulfilled criteria for
      both HSP and HSV.

PMID- 7582701
TI  - Different abdominal scintigraphy pattern in patients with ulcerative colitis,
      Crohn's disease and seronegative spondylarthropathies.
AB  - The aim was to analyse the abdominal scintigraphy pattern in patients with
      seronegative spondylarthropathy (SSp), ulcerative colitis (UC) and Crohn's
      disease (CD). A total of 117 patients with defined histological lesions of
      inflammatory bowel disease (IBD) (68 UC and 49 CD), 32 patients with active SSp
      [European Spondylarthropathy Study Group (ESSG) 1991 criteria] without clinical
      evidence of IBD and 21 controls without IBD or SSp were studied. All patients
      with SSp and controls received similar doses of non-steroidal anti-inflammatory
      drugs. Abdominal scintigraphy images were obtained at 30 and 120 min after
      injection of 99m-technetium hexamethyl propylene amine oxime (99mTc-HMPAO)
      labelled leucocytes. The 99mTc-HMPAO-labelled leucocyte scan was positive in 17
      patients with SSp (53.1%), 45 patients with UC (66.1%) and 33 patients with CD
      (67.3%). Rectum and sigma involvement was more frequent in patients with UC
      (68.8%) than in patients with SSp (23.5%) or CD (33.3%) (P < 0.05) [odds ratios
      (OR): 7.1 and 4.4, respectively]. Terminal ileum involvement was more frequent in
      patients with CD (63.6%) than in patients with SSp (23.5%) or UC (8.8%) (P <
      0.05) (OR: 5.6 and 17.9, respectively). The 99mTc-HMPAO-labelled leucocyte scan
      shows an increased uptake in patients with SSp without evidence of IBD. Perhaps
      these patients represent one end of the spectrum of IBD, but rectal and terminal
      ileum involvement were less frequent in patients with SSp than in patients with
      UC or CD.

PMID- 7582702
TI  - Discordance between objective and subjective assessment of functional ability of
      patients with rheumatoid arthritis.
AB  - The objectives were to investigate whether there is a discordance between
      observed and reported functional ability in patients with rheumatoid arthritis
      (RA) as measured by the Health Assessment Questionnaire (HAQ) and, if so, which
      demographic, clinical and psychological factors contribute to that discordance.
      Fifty-one consecutive RA patients of the out-patient clinic were included. Self
      reported functional ability was compared with the observed performance of tasks
      as described by the HAQ. The amount of discordance was computed by subtracting
      reported scores from observed scores. A positive sign stands for overestimation
      of functional ability by the patient. The average amount of discordance was low,
      0.09 (S.D. 0.39), but showed a large range: -0.88 to 1.00. Multiple regression
      analysis showed that male patients overestimate their functional ability by 0.21
      HAQ units compared with female patients. RA patients overestimate their
      functional ability with increasing disease duration and severity, while RA
      patients in the early stage of the disease tend to underestimate their functional
      ability.

PMID- 7582705
TI  - Are slow-acting anti-rheumatic drugs monitored too often? An audit of current
      clinical practice.
AB  - Rheumatologists usually recommend monthly blood monitoring when patients with
      rheumatoid arthritis (RA) are treated with slow-acting anti-rheumatic drugs
      (SAARDs). Is monthly monitoring needed or could its frequency be reduced? We
      audited the opinions of UK rheumatologists and reviewed clinical experience at
      three centres. To ascertain the interval at which patients are monitored and the
      determinants of monitoring policy we sent a questionnaire to 193 consultant
      rheumatologists; 143 (74%) replied. The majority use monthly monitoring for most
      SAARDs except sulphasalazine, chloroquine and hydroxychloroquine. There is
      extensive variation, which is not related to the type of rheumatology unit or
      whether a shared scheme with general practitioners is used. Reviewing experience
      in 390 patients treated with SAARDs at three adjacent rheumatology units in
      London showed that haematological adverse reactions were infrequent. During 1560
      patient-years of treatment involving 18,720 monthly monitoring visits there were
      13 haematological adverse reactions (11 thrombocytopenias and two leucopenias).
      Five thrombocytopenias developed after 6 months of treatment; five occurred
      gradually over 5 months or more and one borderline low platelet count was seen
      once. The two leucopenias were borderline low white cell counts occurring
      gradually over 3-6 months. Such frequent monitoring is expensive. The total cost
      of monitoring 390 patients for 1560 patient-years was 420,000 pounds. The cost of
      detecting each adverse reaction was 32,000 pounds. Three-monthly monitoring when
      therapy is established after an initial stabilizing period would have identified
      seven out of eight late adverse reactions. Monitoring policies are mainly based
      on clinical consensus with few prospective studies of their value; they need re
      evaluation.

PMID- 7582704
TI  - The aetiopathogenesis of giant cell arteritis.
AB  - In this review, current understanding of the aetiopathogenesis of giant cell
      arteritis is examined. Possible explanations for the late age of onset and
      striking responsiveness to steroid therapy.

PMID- 7582703
TI  - Use of contrast enhanced MRI in the assessment of therapeutic response to a
      disease-modifying antirheumatic drug. Case study of a patient with rheumatoid
      arthritis--6- and 24-month follow up.

PMID- 7582706
TI  - An audit of methotrexate and folic acid for rheumatoid arthritis. Experience from
      a teaching centre.
AB  - We describe an audit of 158 patients with RA treated with weekly methotrexate and
      5 mg of folic acid 24 h later. Our aim was to assess the safety and efficacy of
      this regime in our hands compared with published clinical trials of methotrexate
      in RA, and to examine patient outcomes. Treatment improved ESR, but only 69% of
      patients continuing therapy for prolonged periods believed their arthritis to be
      better on treatment. Health Assessment Questionnaire and Hospital Anxiety and
      Depression questionnaire scores in prospectively studied patients were not
      significantly altered by treatment. Toxicity occurred frequently (59% in those
      continuing and 89% in those ceasing therapy) and cessation of therapy solely due
      to lack of efficacy was rare. The probability of patients continuing with
      methotrexate and folic acid after 1, 2, 3 and 4 yr was 87, 76, 74 and 74%,
      respectively, figures that are at the upper end of the reported range for
      methotrexate alone.

PMID- 7582707
TI  - Evidence of omeprazole-induced small bowel bacterial overgrowth in patients with
      scleroderma.

PMID- 7582708
TI  - Arthropathy, leucopenia and recurrent infection associated with a TcR gamma delta
      population.
AB  - This report documents the presence of clonal gamma delta T-cell receptor (TcR)
      population in the blood of a patient who presented with an arthropathy of
      undetermined cause, leucopenia and splenomegaly. There was no evidence for
      lymphoid malignancy clinically or at post-mortem. The phenotype and genotype of
      the clonal T-cell population were not associated with the predominant TcR delta
      rearrangement found in peripheral blood gamma delta cells, but were similar to
      those found in gamma delta TcR cells infiltrating rheumatoid synovium. The data
      indicate the presence of a monoclonal population of gamma delta cells TcR cells
      which in the face of continued immunosuppression behaved benignly. The case may
      represent a cytomorphologically atypical example of the large granular
      lymphocytes, neutropenia and arthropathy syndrome/lymphoproliferative disease of
      granular lymphocytes and, although the patient's clinical features were not
      'classical', rheumatoid arthritis (RA) may have been the underlying primary
      disorder.

PMID- 7582709
TI  - Destructive lymphadenopathy and T-lymphocyte activation in adult-onset Still's
      disease.
AB  - Recurrent arthritis, fever and lymphadenopathy are symptoms of adult onset of
      Still's disease (AOSD). Differential diagnosis requires the exclusion of
      infections or malignant lymphomas. We report on a case of AOSD showing
      destructive lymphadenopathy, immunophenotyping of peripheral blood leucocytes
      revealed strong activation of T-lymphocytes. Bone marrow biopsy also showed an
      increase of lymphopoietic cells to 23%. Analysis of peripheral blood lymphocytes
      (PBL) after remission showed no remaining signs of activation. Analysis of
      lymphocyte activation by flow cytometry correlated with disease activity.

PMID- 7582710
TI  - Neurological side effects in two patients receiving gold injections for
      rheumatoid arthritis.
AB  - We describe two patients who developed neurological side effects as part of the
      spectrum of nitritoid reactions. Both reactions occurred late in the course of
      treatment. The first patient developed mild nitritoid symptoms and pain in a band
      like distribution, corresponding to T10-T12 dermatomes, shortly after gold sodium
      thiomalate (GSTM) injection. Further injections were followed by similar symptoms
      in addition to paraesthesiae and altered pin-prick sensation of anterior thigh
      and legs with no residual deficit. She has had no further episodes since
      substitution of aurothioglucose. The second patient experienced mild nitritoid
      symptoms following several GSTM injections prior experiencing a cerebrovascular
      accident within several hours of her next injection. She subsequently
      haemorrhaged into the infarcted area with residual neurological deficits. These
      cases highlight that nitritoid reactions can be severe and may be heralded by
      milder symptoms. Patients who develop these reactions whilst receiving GSTM can
      be successfully changed to aurothioglucose.

PMID- 7582711
TI  - Radiological medical joint space narrowing and meniscal lesions. Steering
      Committee of French Society of Arthroscopy.

PMID- 7582712
TI  - Home exercises and out-patient hydrotherapy.

PMID- 7582713
TI  - Serological diagnosis of Lyme disease.

PMID- 7582714
TI  - Lymphocyte subsets in pamidronate-induced lymphopenia.

PMID- 7582715
TI  - The involvement of the gut in the pathogenesis of inflammatory synovitis.

PMID- 7582716
TI  - Measuring outcome in rheumatoid arthritis--which measures are suitable for
      routine clinical use?

PMID- 7582717
TI  - Oncogene expression in synovial fluid cells in reactive and early rheumatoid
      arthritis: a brief report.
AB  - Since it has been implied that cellular oncogenes might have a role in the
      pathogenesis of rheumatoid arthritis (RA), we have examined the expression of c
      myc, c-myb, c-fos, c-jun and c-Ha-ras oncogenes in the cells from synovial fluid
      (SF) and peripheral blood (PB) of patients with reactive arthritis (ReA) and
      early RA. Oncogene expression was studied using RNA hybridizations with 32P
      labelled probes. From the SF, mononuclear and granulocyte cell fractions were
      used separately. Significant differences between ReA and RA were observed only
      for c-myb in PB mononuclear cells and c-jun in SF granulocytes. Regarding the
      expression of c-myc, c-fos and c-Ha-ras oncogenes, no difference between ReA and
      RA was observed. Comparison to normal controls was made using PB mononuclear
      cells; only the expression of c-fos tended to be slightly increased in RA,
      without statistical significance, however. We conclude that oncogene activation
      in the synovial inflammation is not a phenomenon specific for RA.

PMID- 7582720
TI  - Antineutrophil cytoplasmic antibodies in inflammatory arthritis--potential for
      misdiagnosis?
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are well described in Wegener's
      granulomatosis and some forms of vasculitis. They have also been described in
      patients with arthritis, but the specificity of these ANCA and their relationship
      to the presence of vasculitis, antinuclear antibodies (ANA) and granulocyte
      specific ANA (GS-ANA), and to disease activity are uncertain. We studied 101
      patients with forms of inflammatory arthritis and detected four cytoplasmic ANCA,
      eight perinuclear ANCA and 16 atypical ANCA. There was no association between the
      presence of ANCA and ANA or rheumatoid factor. No anti-PR3 antibodies were found
      and no strong anti-myeloperoxidase antibodies were detected. Four GS-ANA were
      detected and were distinct from ANCA. There was no association between rheumatoid
      arthritis disease activity or disability and ANCA status. ANCA did not predict
      vasculitis over a 3 yr follow-up. These ANCA appear to be epiphenomena. Their
      importance lies in their potential to mislead physicians towards a misdiagnosis
      of vasculitis.

PMID- 7582719
TI  - Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis
      and systemic sclerosis.
AB  - We compared the levels of soluble adhesion molecules E-selectin (sE-selectin),
      intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1
      (sVCAM-1) alongside von Willebrand factor (vWf), CRP and rheumatoid factor in 40
      patients in serum by ELISA, rheumatoid factor by sheep red blood cell
      agglutination and CRP by immunonephelometry. Compared to controls, increased sE
      selectin was found in patients with RA (P = 0.0015), vasculitis (P < 0.0003) and
      SSc (P = 0.0126), whilst raised sICAM-1 was found in RA (P < 0.0003), vasculitis
      (P < 0.0003) and SSc (P < 0.0378). sVCAM was lower in RA than in controls (P =
      0.0102), but was unchanged in vasculitis or in SSc. vWF was raised in RA (P =
      0.0102), vasculitis (P < 0.0003) and SSc (P < 0.0003). In a Spearman's rank
      analysis of all the data, vWf correlated with sVCAM-1 and sICAM-1 (both P <
      0.001), sE-selectin with sICAM-1 (P < 0.001) and sVCAM with sICAM-1 (P < 0.005).
      Levels of rheumatoid factor correlated with those of sE-selectin (P = 0.003) and
      sVCAM-1 (P = 0.012), but there were no correlations between any index and CRP.
      The strongest correlations within the RA group were between sICAM and sVCAM (P =
      0.001), in vasculitis it was between sE-selectin and sICAM (P < 0.001), and in
      SSc it was between sE-selectin and sVCAM (P = 0.019). These data suggest that the
      differing levels of vWf, sE-selectin and sICAM-1 in the inflammatory vasculitides
      may be useful in establishing a role for leucocyte/endothelial adhesion in these
      diseases.

PMID- 7582718
TI  - A study of the role of parvovirus B19 in rheumatoid arthritis.
AB  - Serum and synovial tissue from 26 patients with rheumatoid arthritis (RA)
      (according to the diagnostic criteria of the American Rheumatism Association) and
      26 patients with osteoarthritis (OA) were examined. Among the RA group, the
      female to male ratio was 4.2:1, and the age range was 44-82 yr with a mean of
      64.0 yr; joints from which synovium was sampled were hip (n = 12), knee (n = 9),
      ankle (n = 3) and shoulder (n = 2). The duration of rheumatoid disease ranged
      from 6 to 24 yr with a mean of 13.9 yr. Among the OA group, the female to male
      ratio was 2.25:1, and the age range was 51-88 yr with a mean of 68.2 yr; joints
      from which synovium was sampled were hip (n = 18) and knee (n = 8). Twenty-one
      patients from the RA group and 20 patients from the OA group had evidence of
      previous parvovirus B19 infection (serum anti-B19 IgG), and all patients from
      both groups were serum anti-B19 IgM negative. Synovial sections from all 52
      patients were stained with mouse monoclonal antibodies, 3H8 (to B19 capsid
      proteins) and alpha-P (to blood group P antigen). All tissue sections examined
      were found to be negative for both B19 capsid proteins and blood group P antigen.
      Using a nested polymerase chain reaction (PCR) assay, all patients were negative
      for serum B19 DNA. However, B19 DNA was demonstrated in the synovium of 10 of 26
      RA patients and 9 of 26 OA patients; uncorrected chi 2 value = 0.08; degrees of
      freedom = 1; P = 0.77. All 19 patients testing positive for synovial B19 DNA had
      evidence of prior exposure to B19 infection (serum anti-B19 IgG). In conclusion,
      although there is published evidence of chronic rheumatoid-like arthropathy
      following acute parvovirus B19 infection, our findings do not support the
      involvement of B19 in the aetiopathogenesis of RA.

PMID- 7582721
TI  - Behcet's disease in India: a clinical, immunological, immunogenetic and outcome
      study.
AB  - The clinical and laboratory profile of 58 consecutive patients satisfying the ISG
      1990 criteria for the diagnosis of Behcet's disease was analysed. It appears that
      Behcet's disease in India is predominantly 'mucocutaneous' and 'arthritic';
      'ocular' and 'neuro' Behcet's being uncommon. In comparison to published
      literature, the onset of disease in this part of the world is significantly
      delayed. The pathergy test is rarely positive. There is no significant difference
      in clinical presentation and laboratory investigations between children and
      adults with this disease; also, no sex difference was observed. A combination of
      oral steroids and colchicine gives good relief in most cases. Preliminary
      observations seem to reflect no definite association of any known class I antigen
      to disease in this part of the world. A detailed study on immunogenetics is
      underway.

PMID- 7582722
TI  - Arthritis in scleroderma.
AB  - Thirty-four patients (24 females and 10 males) selected from 300 consecutive
      patients with established systemic sclerosis (SSc), with a current or past
      history of articular symptoms, were clinically documented and further studied
      using thermography and bone scan to define the pattern of arthritis. Clinical
      evidence of synovitis was observed in 30 (88%) and joint inflammation was
      detected in 31 (91%) by the above-mentioned imaging techniques. A distinctive
      subset of 10 patients with deforming arthritis was characterized in which seven
      (70%) patients fulfilled criteria for both rheumatoid arthritis and SSC; three of
      these satisfied the criteria for diagnosis of CREST, but none met the criteria of
      mixed connective tissue disease. These patients, as a group, when compared with
      the rest showed limited skin involvement (skin score of 19 +/- 11 vs 33 +/- 14; P
      < 0.05) and were positive for rheumatoid factor (80 vs 13%; P < 0.05) and
      anticentromere antibodies (37 vs 4%; P < 0.05).

PMID- 7582723
TI  - Reactive arthritis: urogenital swab culture is the only useful diagnostic method
      for the detection of the arthritogenic infection in extra-articularly
      asymptomatic patients with undifferentiated oligoarthritis.
AB  - Reactive arthritis (ReA) is a seronegative oligoarthritis triggered by a
      preceding extra-articular infection. While evidence of a microbial infection is
      mandatory for establishing the diagnosis of ReA, the sensitivity of
      bacteriological and serological tests has not been determined in patients without
      symptoms of infection. In a retrospective study, we evaluated the usefulness of
      urogenital swab cultures, serology and stool culture to identify infections in
      234 patients with undifferentiated oligoarthritis. One hundred and forty-four
      patients complaining about joint pain who had no sign or history of inflammatory
      arthritis served as controls. Urogenital swab cultures showed a microbial
      infection in 44% of the patients with oligoarthritis (15% Chlamydia, 14%
      Mycoplasma, 28% Ureaplasma), whereas in the control group only 26% had a positive
      result (4% Chlamydia, 7% Mycoplasma, 21% Ureaplasma) (P < 0.001). A Chlamydia IgG
      antibody titre > or = 1:256 was found in 22% of the patients in the
      oligoarthritis group and in 9% of the controls (P < 0.01). However, for only half
      of Chlamydia IgG-positive patients could a Chlamydia infection be confirmed by
      urogenital swab culture. Twenty-one per cent of patients with oligoarthritis vs
      23% of the controls had positive antibody titres for Salmonella (not
      significant), 15% vs 5% for Yersinia (P < 0.05) and 17% vs 3% for Borrelia IgG (P
      < 0.01). In two patients, stool cultures were positive for Campylobacter.
      Urogenital swab culture is a sensitive diagnostic method to identify the
      triggering infection in ReA. A single determination of antibodies against
      Chlamydia trachomatis is of limited value because of the high prevalence of
      positive results in the control group.

PMID- 7582724
TI  - Gout in patients attending the rheumatology unit of Lome Hospital.
AB  - A retrospective study was carried out to determine the semiological and
      aetiological profiles of gout in patients attending a hospital clinic in Lome,
      Togo. Gout was diagnosed in 106 of the 3517 patients seen from October 1989
      through October 1993. Clinical findings and hyperuricaemia were the basis for the
      diagnosis of gout in 88 patients. In the remaining 18 patients, monosodium urate
      crystals were demonstrated in synovial fluid in addition. One hundred and five
      patients were male. The mean age at disease onset was 45 yr and the mean duration
      of the disease was 8 yr. Twenty patients (19%) had tophi. None of the patients
      had a history of renal colic. The ankle, the knee and the first
      metatarsophalangeal joint were the joints most often affected. Sixty-three
      patients (59%) had a monoarticular involvement, whereas an oligo- or
      polyarticular involvement was observed in the remaining 43 patients. Twelve
      patients (11%) had a familial history of gout. Forty patients (38%) were obese
      and 78 (74%) were habitual drinkers. Forty-one patients (39%) had hypertension
      and 17 of them were under diuretic therapy. While more work is needed before
      drawing a definite conclusion, this study is in striking contradiction with the
      common belief that gout is exceedingly rare in Black Africa. The risk factors in
      Togo seem to be no different from those observed in Caucasians.

PMID- 7582725
TI  - In-patient treatment for active rheumatoid arthritis: clinical course and
      predictors of improvement.
AB  - The objective was to determine the clinical course and predictors of clinical
      response in patients with rheumatoid arthritis (RA) who are hospitalized for
      active disease and functional deterioration. Sixty-three patients who were
      admitted to a rheumatology clinic for multidisciplinary treatment were
      prospectively evaluated at 2-weekly intervals. During the admission period, which
      lasted for a mean of 47 +/- 24 days, patients improved significantly according to
      variables of disease activity, functional status and emotional status. The change
      in the variables appeared to be linear with time. Twenty-seven patients (43%)
      fulfilled the Paulus 20% criteria for clinical response during treatment. A long
      disease duration, a high Larsen erosion score, a high level of disease activity
      at admission and the institution of a disease-modifying anti-rheumatic drug
      within 3 months before admission were associated with a clinical response. In
      patients hospitalized for active disease, improvement appeared to be linear with
      time during admission. Patients with long-standing, destructive disease and a
      high level of disease activity improved most during hospitalization.

PMID- 7582726
TI  - Surgery to the ankle.

PMID- 7582728
TI  - Painful knees associated with a septic focus.
AB  - The association between gastrointestinal disorders and arthritis is well
      recognized. We describe a 54-yr-old man who presented with a seronegative
      oligoarthritis in whom the clinical picture was consistent with a hypertrophic
      osteoarthropathy. An occult septic focus was identified when a barium enema
      demonstrated a diverticular abscess, treatment of which led to a complete
      resolution of symptoms.

PMID- 7582727
TI  - Malabsorption caused by coeliac disease in patients who have scleroderma.
AB  - Coeliac disease may account for malabsorption in scleroderma patients even when
      test suggest bacterial overgrowth. A small bowel biopsy is essential.

PMID- 7582729
TI  - Adult- and childhood-onset systemic lupus erythematosus: a comparison of onset,
      clinical features, serology, and outcome.
AB  - This study examines the differences which may distinguish systemic lupus
      erythematosus (SLE) presenting in adult life or childhood. A common database was
      established, with analysis of clinical, serological and outcome features of a
      cohort of patients with SLE, with disease diagnosed before the age of 16 (n = 39)
      or after the age of 16 (n = 165). Disease onset was generally more severe in the
      childhood-onset patients. Cardiopulmonary disease was more common in the older
      onset group, but major haematological manifestations were more frequent in the
      childhood-onset group. Serologically, anti-DNA, anti-Sm and anti-RNP antibodies
      and a low C3 were all found more frequently in the younger patients. Twice as
      many adult-onset cases had died at the time of the last follow-up (10 vs 5%), but
      this group had been followed for a longer period (average 7.5 yr, S.D. 3.9 for
      adults vs average 4.8 yr, S.D. 3.2 for children). However, the younger patients
      were twice as likely (82 vs 40%) to require high-dose prednisone, although the
      requirement for immunosuppressive agents was similar in the two groups.
      Clinicians should anticipate that children with SLE have a more severe disease
      onset than adults in general.

PMID- 7582731
TI  - Anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies are
      not increased in Kawasaki disease.
AB  - We studied anti-neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial
      cell antibodies (AECA) in 58 children with acute Kawasaki disease (KD) before
      i.v. gamma globulin treatment, 35 children with infection and fever > 38.5
      degrees C, and 48 healthy afebrile children. ANCA were studied by indirect
      immunofluorescence (IIF) on ethanol-fixed neutrophils and by ELISA with crude
      neutrophil extract as antigen. AECA were studied using ELISA on resting and
      activated endothelial cells. ANCA IIF was weakly positive, cytoplasmic, diffuse
      and homogeneous in all three groups. ANCA IIF, ANCA ELISA and AECA ELISA were no
      higher in KD than in febrile children. There was no difference between KD with
      and KD without coronary artery aneurysms. AECA differences between the KD and
      afebrile group were not significant after correction for total IgM. In contrast
      with our previous findings, we conclude that ANCA and AECA are not raised in KD
      compared with febrile controls. It therefore seems unlikely that they are
      important in the pathogenesis of vasculitis in KD.

PMID- 7582730
TI  - Antiphospholipid antibodies in paediatric systemic lupus erythematosus, juvenile
      chronic arthritis and overlap syndromes: SLE patients with both lupus
      anticoagulant and high-titre anticardiolipin antibodies are at risk for clinical
      manifestations related to the antiphospholipid syndrome.
AB  - Antiphospholipid antibodies (APA) are often associated with severe clinical
      manifestations, especially in the setting of systemic lupus erythematosus (SLE).
      Here we have investigated the prevalence of anticardiolipin antibodies (aCL) and
      lupus anticoagulant (LA) in paediatric patients affected with SLE, JCA and
      overlap syndromes (OS) and correlated the presence of aCL and LA with clinical
      features. aCL were assayed by enzyme-limited immunoassay; LA was determined by
      activated partial thromboplastin time and the kaolin clotting time test. aCL and
      LA assays were performed in parallel on at least two occasions over a 7-30-month
      follow-up. Fifteen out of nineteen (79%) SLE patients had aCL and 8/19 (42%) had
      LA. Six SLE patients displayed manifestations that were APA-related: deep venous
      thromboses, autoimmune haemolytic anaemia, pulmonary hypertension, neurological
      alterations. Five out of six symptomatic patients had both LA and high-titre aCL.
      In contrast, JCA and OS patients had usually low-titre aCL, no detectable LA and
      no APA-related manifestations. aCL persisted at high titre over time in SLE
      patients, but was only transiently detected in JCA and OS patients. This study
      shows that the simultaneous positivity for LA and high-titre aCL allows the
      identification of paediatric SLE patients who are at risk not only for
      thrombosis, but also for other APA-related clinical features.

PMID- 7582732
TI  - Successful management of reactive haemophagocytic syndrome in systemic-onset
      juvenile chronic arthritis.

PMID- 7582733
TI  - Gynaecological symptoms in fibromyalgia.

PMID- 7582735
TI  - Non-surgical management of the carpal tunnel syndrome.

PMID- 7582734
TI  - Is remitting seronegative symmetrical synovitis with pitting oedema (RS3PE
      syndrome) associated with HLA-A2?

PMID- 7582736
TI  - VIP in salivary glands in Sjogren's syndrome.

PMID- 7582738
TI  - Quinine for nocturnal leg cramps.

PMID- 7582737
TI  - The well-built clinical question: a key to evidence-based decisions.

PMID- 7582739
TI  - Proceedings of the International Seminar on National Health Promoting Policies,
      Strategies and Structures. Paris, France, November 21-23, 1994.

PMID- 7582740
TI  - Health promotion policies, strategies and structures.

PMID- 7582741
TI  - [Proceedings of the International Seminar on National Health Promoting Policies,
      Strategies and Structures. Welcome by the French government].

PMID- 7582742
TI  - [Health promotion at the heart of the objectives and policies of the European
      Community].

PMID- 7582743
TI  - Comparing health promoting policies, strategies and structures: rewards and
      challenges.

PMID- 7582745
TI  - Health promotion and education in Australia. Case study.

PMID- 7582744
TI  - [Health promotion and education in France. Case studies].

PMID- 7582746
TI  - An unpredictable mix ...

PMID- 7582747
TI  - Health promotion and education in England. Case study.

PMID- 7582750
TI  - Country report. Canada.

PMID- 7582748
TI  - Health promotion and education in Finland. Case study.

PMID- 7582752
TI  - Country report. Greece.

PMID- 7582751
TI  - Country report. Germany.

PMID- 7582753
TI  - Country paper. Hungary.

PMID- 7582749
TI  - International Seminar on National Health Promoting Policies, Strategies, and
      Structures. Paris, November 21-23, 1994. Report and recommendations.

PMID- 7582754
TI  - Country report. India.

PMID- 7582757
TI  - Proceedings of the International Seminar on National Health Promoting Policies,
      Strategies and Structures. Theme and purpose.

PMID- 7582756
TI  - Country report. Kenya.

PMID- 7582755
TI  - Country report. Indonesia.

PMID- 7582758
TI  - Country report. The Netherlands.

PMID- 7582759
TI  - Country report. Norway.

PMID- 7582760
TI  - Country report. Sweden.

PMID- 7582763
TI  - Developing health promotion in Estonia.

PMID- 7582761
TI  - Country report. United States of America.

PMID- 7582762
TI  - Strategic planning for health promotion in a decentralised system: the Flemish
      experience.

PMID- 7582769
TI  - [Assessment of the effectiveness of noninvasive immunoenzyme method in the
      detection of Staphylococcus aureus alpha-hemolysin in the washings of nasal
      mucosa and saliva of healthy individuals].
AB  - The efficacies of detection of S. aureus by the bacteriologic method and enzyme
      immunoassay test system based on F(ab)2 fragments of purified antistaphylococcal
      antibodies were compared. Washings off the nasal mucosa and salivary samples from
      20 normal subjects (medical staff) were examined. The number of findings of S.
      aureus by the detection of its a-hemotoxin in primary samples was much higher and
      the time of analysis two times shorter with enzyme immunoassay.

PMID- 7582767
TI  - [Methodical bases of the use of erythrocytic diagnostic agents as phagocytosis
      objects].
AB  - The error in assessment of the neutrophil phagocytic activity is 5.8%. This is
      attained by removal of conglomerations of phagocytosis objects and by ruling out
      the minimal variations in the duration of contact between the blood and foreign
      corpuscles and preparation of smears to be examined on the same slide. The
      content of up to 90% red cells does not influence the neutrophil phagocytic
      activity, and higher concentration reduces its level.

PMID- 7582766
TI  - [Possibilities of indication of anti-Hb core IGM in the saliva of patients with
      hepatitis B].
AB  - A method for measurements of anti-HBcore IgM in the saliva has been developed.
      The levels of anti-HBcore IgM in the blood sera and saliva were compared in 62
      patients with acute viral hepatitis B. The results of anti-HBcore IgM indication
      in samples of blood serum and saliva completely coincided, this permitting us to
      recommend assays of this parameter in the saliva when examining patients with
      hepatitis B, in order to reduce the number of blood collections.

PMID- 7582768
TI  - [Determination of individual sensitivity of peripheral blood lymphocytes to
      cytostatic agents and hormones].

PMID- 7582764
TI  - [Current methods of immunological and genetic diagnosis of HIV infection
      (literature review)].

PMID- 7582765
TI  - [A model for the assessment of fibroblast morphology].
AB  - A model for comprehensive assessment of morphologic parameters of a cell (area,
      nucleus and cytoplasm area, degree of spreading), based on the use of a scanning
      device, has been developed. The model comprises an original method for staining
      the preparations, which permits assessment of the degree of cell spreading by
      microdensitometry, and updating the equipment and software. The programs help
      assess the integral and derivative parameters, such as the area of the interface
      zone of a cell, the shape factor, spreading, and nucleus to cytoplasm ratio.
      Using this model, the effect of peripheral blood mononuclears on the morphology
      of transformed murine fibroblasts L929 upon a contact exposure was assessed.
      Addition of mononuclears to fibroblast culture led to alteration of their
      morphology: increase of the mean cellular area, degree of spreading, and of shape
      factor and reduction of the nucleus/cytoplasm ratio. This was true for both the
      mean values and the population composition.

PMID- 7582772
TI  - [Quality control in cytological studies].

PMID- 7582771
TI  - [Trials of a method for assessing thromboplastic activity of monocytes in the
      newborn].
AB  - Trials of a method for assessment of thromboplastic activity of monocyte
      macrophages in 58 healthy full-term babies in the first days of life, when the
      hemostasis system undergoes essential changes, revealed an appreciable reduction
      of the basal thromboplastic activity of monocytes and of its level after 4-hour
      incubation of these cells on days 3-5 after birth, this reduction being
      paralleled by progressive hypocoagulation (as shown by coagulogram). The degree
      of reduction of the thromboplastic activity of monocytes was directly
      proportional to an increase in the level of fibrin-monomer complexes and
      fibrinogen degradation products in the blood plasma and serum. This indicates a
      possible decrease of the production of vitamin-K-dependent coagulation factors
      not only in the liver, but in monocytes as well. On the other hand, the detected
      shifts indicate that reduction of thromboplastic activity of monocytes in
      parallel with increased thrombin formation in the blood are biologically
      justified, for this decrease equilibrates the thrombogenic shifts in the system
      of neonatal hemostasis.

PMID- 7582773
TI  - [Significance of heparin elimination from plasma in the assessment of coagulogram
      and antithrombin III activity].
AB  - An original adsorbent for non-fractionated and low-molecular weight heparin
      (fraxiparin,Sanofi) has been developed and tried in experiments and in a clinical
      setting. Tests carried out in 58 patients with disseminated intravascular
      coagulation and thromboses treated with heparin demonstrated the possibility of
      obtaining objective data on the status of the blood clotting system. Heparin
      adsorption is particularly important in measurements of heparin III activity, for
      even low concentrations of heparin mask the defect of this anticoagulant.

PMID- 7582774
TI  - [Blood sodium].

PMID- 7582770
TI  - [Development of a method of obtaining lyophilized antileukocyte histotyping sera
      intended for long-term storage].
AB  - An optimal scheme for sublimation of anti-HLA-sera of locuses A, B, C, and DR has
      been developed, consisting of freezing at 60 degrees C and lyophilization to 29
      30 degrees C, this permitting the preparation of initially active antileukocytic
      sera. The activity and specificity of defrosted native and lyophilized anti-HLA
      sera were assessed in the complement-dependent cytotoxicity test. Four-year
      follow-up of the activity of dried anti-HLA-sera showed that the stabilizer was
      not needed, for the activities of the sera lyophilized with and without it was
      virtually equally high. The optimal storage temperature for dry anti-HLA-sera is
      4 degrees C.

PMID- 7582775
TI  - [Mathematical assessment of the degree of changes in the level of lipids and
      intensity of lipid peroxidation in cerebrovascular diseases].

PMID- 7582776
TI  - [Possibilities of the cytological method in intraoperative diagnosis of pigmented
      tumors of the skin].

PMID- 7582778
TI  - [Chemiluminescence of blood and urine in the differential diagnosis of
      hemorrhagic fever with renal syndrome].

PMID- 7582781
TI  - [Optimizing conditions of cell culture use for virus indications by means of
      fluorescent probes].
AB  - Cell cultures in a suspension on medium 199 with 1 x 10(6) cells per ml are
      recommended for virus indication by means of fluorescent probe method. When
      stored at 4 degrees C, the cells are fit for work for 5 days. The proposed
      conditions for the use of cell cultures are necessary for effective introduction
      of the fluorescent probe method in practical virological laboratories.

PMID- 7582777
TI  - [The binary ratio method: new possibilities in solution of research and
      differential diagnosis tasks].
AB  - Binary ratio is the key notion in the general theory of systems, a generalization
      of functional relationship. A clinical laboratory parameter or sign is merely an
      element of the analyzed information system, and situations are possible when
      signs analyzed separately without consideration for their interrelationships are
      not informative at all, whereas the structure of binary ratio helps solve
      differential diagnostic problems and other tasks. The information reflected in
      binary ratios characterizes the relationships between signs and the intricate
      features in the vital activity of the organism, such as mechanisms of regulation,
      homeostasis, etc. A method for assessment and comparison of the structure of
      binary ratios is described as a new method for analysis of biomedical data. The
      method is realized in a research system OMIS (PC-based) and was tried in the
      solution of complex problems in hematology, pulmonology, cardiology, oncology,
      etc.

PMID- 7582782
TI  - [Stages of the cytological diagnosis in breast cancer].

PMID- 7582779
TI  - [Rapid methods in microbiological examinations of the blood].
AB  - Two rapid (pilot) methods for the determination of blood microflora are compared.
      One of them is based on bacterioscopy, the other on culturing of bacteria. Use of
      these methods helps increase the detection rate of microorganisms in the blood
      from 34.8 to 59.6% in a shorter time, 1-3 days instead of 5-7. No additional
      staff or sophisticated equipment and tests kits are needed for the tests. The
      methods are recommended for research and clinical laboratories.

PMID- 7582783
TI  - [Carcinoembryonic antigen: experience in the study of its expression at the
      tissue and cellular levels (the 30th anniversary of its discovery)].

PMID- 7582780
TI  - [Effects of solar and geomagnetic activity on the accuracy of laboratory methods
      in differentiation of Staphylococcus aureus and S. epidermidis].
AB  - The production of three obligatory enzymes (DNAse, RNAse, gelatinase) and of
      three facultative ones (lecithinase, a-hemolysin, plasma coagulase) by six
      strains of S. aureus, namely, 209, Smit, Wood 46, phagotype (3A, 3C, 71), (53,
      75, 84, 85), and (52A, 79), was investigated, as was the activity of twenty
      taxonomic parameters in comparison with the cyclic changes of solar activity and
      magnetic field of the Earth. The follow-up period was two years, from 1988
      through 1989. The measurements were taken once a month. Solar activity and
      geomagnetic field of the Earth were found to influence the autofluctuations of
      the parameters used to discriminate between S. aureus and S. epidermidis. The
      activity of formation of pathogenicity enzymes DNAse, RNAse, and gelatinase in
      the course of a year varied within a wide range: two- to ten-fold. Changes in the
      aggressive activity of staphylococci were characterized by a cyclic pattern with
      the cycle duration of about a year. Of the biochemical parameters the most labile
      were capacity to oxidize lactose, xylite, and D-melibiose, to hydrolyze urea, and
      the Voges-Proskauter test.

PMID- 7582784
TI  - [Mitotic regimen of non-Hodgkin's lymphoma].
AB  - The mitotic regimen of non-Hodgkin's lymphomas (n = 86) and of reactive
      follicular hyperplasia (n = 14) has been studied. A correlation between the
      parameters of mitotic regimen and morphologic degradation of malignant lymphomas
      has been revealed. Blastic forms of lymphomas were found to be characterized by
      the highest mitotic activity with a greater number and variety of forms of
      pathologic mitoses (p < 0.001). The frequency of mitoses in lymphomas of low
      malignancy was found to be reliably reduced in comparison with that in follicular
      hyperplasia (p < 0.01). The results of assessing the mitotic regimen are
      recommended to be used for the differential diagnosis and subclassification of
      non-Hodgkin's lymphomas.

PMID- 7582785
TI  - [Cardiovascular diseases in motor vehicle drivers and traffic safety].
AB  - Epidemiologic, electrophysiologic and psychophysiologic studies among urban and
      rural automobile drivers helped to reveal occurrence of coronary artery disease
      (CAD), arterial hypertension (AH) and their risk factors. In addition, special
      studies (monitoring of ECG in natural conditions) among 118 drivers diagnosed the
      signs of coronary failure and arrhythmias. Psychophysiologic studies among the
      individuals suffering from cardiovascular diseases (CAD, AH and arrhythmias)
      proved worse parameters important for occupational activities and for traffic
      safety.

PMID- 7582789
TI  - [Manganese poisoning].

PMID- 7582788
TI  - [Occupational hygiene in major production of polyvinyl chloride].
AB  - The article deals with results of manifold hygienic examination of work
      conditions at major production of polyvinylchloride. The authors evaluated
      hardness and intensity of the work and analyzed the morbidity with transitory
      disablement.

PMID- 7582786
TI  - [Morphological changes in the gastric mucosa in workers with chronic mercury
      poisoning].
AB  - The authors studied morphologic changes in gastric lining of patients facing
      chronic mercuric intoxication. The examinees are former burners at metallurgic
      plant of Khaidarkansk mercuric enterprise. The patients demonstrated significant
      destruction of the superficial epithelial cells and the accumulation of
      Campylobacter piloridis. The parietal and zymogen cells appeared to have
      depressed functional activities. The cells in gastric antrum had ultrastructure
      characterized by vacuoles with dense filaments which could be a morphologic
      marker of mercuric intoxication.

PMID- 7582787
TI  - [Effects of age and length of service on the state of the renin-angiotensin
      aldosterone system and prostaglandin synthesis in coal miners].
AB  - Radioimmune assay determined serum renin activity, serum aldosterone level and
      its excretion with urine, amounts of thromboxane A2 (TxA2), prostacyclins PgI2
      and PgF2a in urine of 76 apparently healthy miners before and after the working
      shift. Conventional techniques were used for estimation of blood and urine
      electrolytes and creatinine. In this connection activity of renin-angiotensin
      aldosterone system (RAAS) in the miners before and after the work appeared to
      depend on the age and the length of service, to reach the maximum at the age of
      31-40 and at 11-15 years of the service. Afterwards the activity lowered. The
      miners older than 41 had RAAS response decreased or absent after the work. Ratio
      TxA2 PgI2 remained unchanged in the miners over age of 41, whereas in the younger
      miners the ratio considerably decreased during the work.

PMID- 7582790
TI  - [Detection of oxime-2-methyl-1-diethylamine butanone-3+ inhibitor in the
      workplace air by thin-layer chromatography].
AB  - The authors elaborated a method to detect inhibitor of oxime-2-methyl-1
      diethylamine butanone (amino oxime) in the air of workplace by means of thin
      layer chromatography. If "Silufol" plates used, the total error does not exceed
      +/- 19.3%. Lower limit of the detection is 3 mg/m3.

PMID- 7582792
TI  - [Allergic diseases in workers producing household chemical products].
AB  - The examination covered 143 individuals engaged into production of synthetic
      foaming and paste-forming detergents, cosmetic and hygienic aerosols. Polls,
      immunologic surveys and specific allergologic examination revealed that 40% of
      the subjects had immunologic disorders and allergies, and 72% of this share was
      occupied by the workers of the aerosol production. Skin allergic diseases were
      prevalent. The risk factors for allergic diseases could be traced to congenital
      propensity, joint effects of multiple chemicals. All the employees at placement
      should undergo specific allergologic examination by means of general set of non
      infectious allergens and determination of serum IgE level.

PMID- 7582791
TI  - [Toxicity dynamics of anionic dyes in the air of a work place and long-term
      effects after absorption through the skin].
AB  - The study covered 10 types of anion dyes for leather: Crimson 4RT, Gray M, Solid
      Blue, Red 8S, Black N, Brown 46, 673, 911, 551, 557. According to LD50 criterion
      they all were assigned to IV jeopardy class. It instilled per os 30 times, the
      chemicals induced mild hemotoxic effect similar to that of methemoglobin-formers,
      in half of the cases affected gonads. Allergic and local irritating skin effects
      were unusual. Solid Blue and Crimson 4RT dyes were subjected to inhalation
      trials. Limcf for those two equal 51.8 and 38.0 mg/m3 respectively Limch--8.3 and
      7.1 mg/m3, measured through changes in red blood parameters, behavioral response
      and other reactions. With consideration of Limch, toxicity for gonads and
      embryos, mutagenicity, the authors justified the MAC for Crimson 4RT dye in the
      air of workplace--1 mg/m3 (II jeopardy class), for Solid Blue dye--5 mg/m3 (III
      jeopardy class).

PMID- 7582794
TI  - [Methodological approaches to the use of ECG monitoring in physical
      examinations].

PMID- 7582797
TI  - Worked out: Working Paper 10.

PMID- 7582793
TI  - [Characteristics of eye diseases in workers of biochemical and mill enterprises].

PMID- 7582795
TI  - [Functional state of the liver in workers exposed to multi-component chemical
      mixture in the production of plastic construction materials].
AB  - The examination covered 52 workers engaged into production of linoleum and
      polyvinylchloride self-sticking coating. The workers were exposed to mixture of
      chemicals, especially to low concentrations of diethylhexyl phthalate (dioctyl
      phthalate). Detoxication in the liver was assessed through developed antipyrine
      test with detection of total and free derivatives of antipyrine in the urine. If
      compared to other functional tests, the changes in activity of enzymes dependent
      on cytochrome P-450 were considerably prevalent and marked. Divergent changes
      were seen--activated enzymes of antipyrine oxidation (I phase of the metabolism)
      and depression of those participating in the metabolites conjugation. The
      findings were considered as molecular results of toxic influence on the liver.

PMID- 7582796
TI  - [Ischemic heart disease in workers of radiochemical industry chronically exposed
      to radiation dosage less than MPEL].
AB  - Prevalence of coronary artery disease (CAD) was studied in workers of atomic
      industry, who are exposed to combined radiation (doses hardly allowable for
      professionals). The occupational activities lasting for 5 to 38 years caused
      total gamma-radiation, doses of 0.01-1 Gy, plutonium-239 incorporation of 0.07
      1.48 kBq. The prevalence of CAD, with consideration of Minnesota Code Criteria,
      equalled 10.9%. The authors analyzed the main risk factors for CAD. Dispersion
      analysis failed to find significant relationship between CAD and the total dose
      of external radiation and the level of plutonium-239 incorporation. The studies
      revealed reliable dependence of the CAD occurrence on the age and arterial
      hypertension.

PMID- 7582798
TI  - Tune in to your patients' views.

PMID- 7582799
TI  - Consumers talk back on cancer care.

PMID- 7582800
TI  - Shapeless figures.

PMID- 7582801
TI  - So you think that you can interview?

PMID- 7582802
TI  - Save cash in community.

PMID- 7582803
TI  - Everything is super in the world of nurse executive directors.

PMID- 7582805
TI  - Nurse executives: buying in or selling out?

PMID- 7582804
TI  - Give up your power. Interview by John Naish.

PMID- 7582806
TI  - Conditioned pleasure attenuates the startle response in rats.
AB  - The acoustic startle response of rats was found to be attenuated if elicited in
      the presence of a conditioned stimulus predicting reward. During conditioning,
      animals received a total of 21 pairings of light with palatable food and sucrose
      solution, whereas controls received food and sucrose in the absence of light. The
      amplitude of the acoustic startle response was significantly reduced in the
      presence of light in conditioned animals, but not in controls. It is assumed that
      a conditioned response to light is the activation of a central state of pleasure.
      We therefore suggest that "pleasure-attenuated startle" reflects a mechanism by
      which a defensive or aversive response is attenuated during a pleasant, hedonic
      state.

PMID- 7582807
TI  - Effects of the Ca2+ channel antagonist flunarizine on visual discrimination
      learning.
AB  - Recent studies report that the peripheral administration of Ca2+ channel
      antagonists improves memory while central administration impairs memory in
      neurologically intact subjects. This study compares the effects of systemic
      versus central administration of the Ca2+ channel antagonist flunarizine on
      visual discrimination learning. In Experiment 1, 60 five-day-old male chicks
      received an intraperitoneal injection of 0, 1, 10, or 25 mg/kg flunarizine. Each
      chick then received three post-treatment test sessions (+5 min, +30 min, and +24
      h) consisting of 60 visual discrimination trials followed by 5 min of observation
      in an open field. Flunarizine produced a dose- and time-dependent facilitation of
      learning. Evaluation of open-field behaviors indicated that the dose of
      flunarizine required to increase spontaneous activity was 10 times higher than
      the dose required to facilitate visual discrimination learning. No other open
      field behaviors were effected. In Experiment 2, 44 chicks received
      intracerbroventricular injections of 0, 100 nM, 100 micro M, or 1 mM flunarizine
      followed by visual discrimination training as described in Experiment 1.
      Ventricular injection of flunarizine significantly increased the number of errors
      made during acquisition and retention trials. These data are consistent with
      earlier studies showing that systemic, but not central, administration of Ca2+
      channel antagonists facilitates learning.

PMID- 7582808
TI  - L-nitroarginine reduces hippocampal mediation of place learning in the rat.
AB  - Based on previous results it was hypothesized that the neural substrate of the
      acquisition of place learning during inhibition of the nitric oxide synthesizing
      enzyme (NOS) by L-nitroarginine (L-N-ARG) differs from the neural substrate of
      normal task acquisition by a reduced or abolished participation of the
      hippocampus. This hypothesis was tested in two independent experiments. In
      Experiment 1 the behavioral consequences of bilateral transection of the fimbria
      fornix--a lesion that abolishes normal hippocampal function--were investigated in
      animals that had acquired the task after either a vehicle control pretreatment or
      a 5-day pretreatment period during which near-total inhibition of NOS had been
      accomplished by L-N-ARG injections. While fimbria-fornix transections
      significantly impaired task performance in normal animals the rats which had
      acquired the task during NOS inhibition did not reveal a lesion-associated
      impairment. In Experiment 2 four groups of rats were studied: two groups
      initially received bilateral transection of the fimbria-fornix, while the two
      others were subjected to sham surgery. Subsequently, one of the fimbria-fornix
      transected and one of the sham-operated groups received a 10-day period of L-N
      ARG injections, while the two remaining groups received saline control
      injections. During the final 5 days of injections the four groups were subjected
      to training on the place-learning task. While NOS inhibition clearly impaired
      task acquisition in the sham-operated animals, L-N-ARG administration in fimbria
      fornix-transected animals failed to impair place-learning acquisition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582810
TI  - Both electrolytic and excitotoxic lesions of nucleus accumbens disrupt latent
      inhibition of learning in rats.
AB  - Evidence indicating a role for the nucleus accumbens in the development of latent
      inhibition of learning has accumulated. Two experiments were conducted using
      Wistar rats to investigate this role directly. Experiment 1 used a conditioned
      emotional response paradigm to assess the effects of discrete electrolytic
      lesions in the shell region of the nucleus accumbens. Latent inhibition was
      attenuated by this lesion. In order to determine the contribution made by damage
      to fibers en passage associated with electrolytic lesions, Experiment 2 assessed
      the effects of NMDA-induced lesions in the shell of the nucleus accumbens in the
      same task. Latent inhibition was again significantly attenuated. These findings
      support the proposition that an intact nucleus accumbens is necessary for the
      normal development of latent inhibition.

PMID- 7582811
TI  - Inter-session delay and its effects on performance and retention of spatial
      learning on a radial maze with mice.
AB  - Spatial learning on the radial maze was studied in two inbred strains of mice
      (C57BL/6 and DBA/2). Five different periods of delay (no delay, 40 min, 2, 8, and
      24 h) were inserted between sessions in order to analyze the role of this inter
      session delay on training and on retest 1 month later. Results showed that
      learning profiles and performance levels varied widely with inter-session delay.
      When the delay was very short (no delay and 40 min), mice of both strains were
      incapable of learning the task but when the delay was more than or equal to 2 h,
      the mice succeeded very quickly. The inter-session delay also influenced the
      performance of mice in the 1-month retention test. C57BL/6 mice obtained good
      performances in the procedure including a 2-h inter-session delay, while DBA/2
      mice obtained good performances with 2- and 8-h delays. These results demonstrate
      the importance of the procedure in complex spatial learning.

PMID- 7582809
TI  - Song isolation is associated with maintaining high spine frequencies on zebra
      finch 1MAN neurons.
AB  - Male zebra finches normally learn much of their song during the second month
      after hatching. This is a period of rapid change throughout the brain. We studied
      anatomical consequences of manipulating exposure to song. We investigated neurons
      of lateral MAN (1MAN), a nucleus implicated in song learning (Bottjer et al.,
      1984), in male and female zebra finches (Taeniopygia guttata) at 55 days
      posthatch. Birds were raised either under normal colony conditions (social) or in
      colonies in which adult males were removed when the young hatched (song
      deprived). Brains were stained with the Golgi-Cox method. Fine morphological
      details of spiny 1MAN neurons were recorded with a 3D semiautomated computer
      system. Several features of the spiny 1MAN neurons differ between sexes. Males
      have neurons with larger somata, more primary dendrites and thicker dendrites,
      than neurons from females. These features as well as dendritic length and other
      branching characteristics do not differ between treatment groups. There is a
      large difference in dendritic spine frequencies between the social and the song
      deprived groups. Social, song-experienced males have spine frequencies 41% lower
      than song-deprived males. In females, spine frequencies are as high as in the
      song-deprived males and do not differ between the song-deprived and social
      conditions. Developmental overproduction and subsequent pruning of neural
      connections have been observed in many areas of the central nervous system. We
      suggest that apparent pruning in 1MAN is modulated by experience: It takes place
      if the social experiences associated with auditory song learning have occurred.
      This finding is consistent with the synapse selection hypothesis of Changeux and
      Danchin Brain Research, 309, (1976) and with data found using an acoustic filial
      imprinting paradigm in the domestic chicken.

PMID- 7582812
TI  - Early environmental stimulation produces long-lasting changes on beta
      adrenoceptor transduction system.
AB  - Long-term behavioral and biochemical effects of exposure to differential early
      stimulation (postnatal handling and/or enriched environment) were studied in 18-
      to 20-month-old Sprague-Dawley rats. Postnatal handling treatment was given
      between 1 and 22 postnatal days. In the enriched environment procedure, the pups
      were maintained under enriched conditions from weaning until postnatal Day 100.
      At 18 months of age animals were tested for working memory in an object
      recognition test, based on the differential exploration of familiar and new
      objects. Animals reared in the enriched environment performed better in the
      working memory test than did control or postnatally handled rats. No interaction
      was observed between postnatal handling and environmental enrichment on cognitive
      parameters. At 20 months of age, the animals were sacrificed and cyclic AMP
      formation was determined under basal conditions and after activation of beta
      adrenoceptors in cerebral cortex and hippocampus. Both postnatal handling and its
      combination with exposure to enriched environment significantly increased basal
      cyclic AMP accumulation in cerebral cortex, but not in the hippocampus.
      Environmental enrichment was able to induce a long-lasting modification in the
      responsiveness of the beta-adrenergic neurotransmitter system as reflected by a
      decreased cyclic AMP accumulation after beta-adrenoceptor activation by means of
      isoprenaline, in either anatomical structure. It is suggested that manipulations
      of the environment early in life leading to a reduction in age-related memory
      deficits produce subtle but long-lasting modifications of noradrenergic
      transmission.

PMID- 7582813
TI  - Spatial exploration in transgenic mice expressing human beta-S100.
AB  - beta-S100 is a calcium-binding protein in the CNS which is involved in the
      development of the nervous system. In addition, it has been postulated to play a
      role in long-term potentiation (LTP) in the hippocampus. To test its role in
      behavior related to hippocampal function, the gene was overexpressed (80 copies)
      in CD-1 transgenic mice, and the exploration of a novel environment was examined
      in two experiments. In both experiments subjects' exploratory behavior was
      observed in an open-field arena containing four objects. No differences in
      emotional behavior were found between transgenic mice and their controls as
      measured by the subjects' motility, defecation, and urination. The results of
      Experiment 1 revealed that transgenic mice explored objects significantly less
      than the controls, and they did not respond overtly to the spatial change after
      object displacement. The control CD-1 subjects, on the other hand, showed
      increased selective reexploration of the displaced object. The results of
      Experiment 2 replicated the findings of Experiment 1 and revealed more subtle
      differences in object exploration between the groups. Transgenic mice climbed
      objects less often and they had longer latencies of object approach than normal
      CD-1 mice. The study suggests the possible involvement of beta-S100 protein in
      general exploratory behavior, which includes learning of spatial characteristics
      of the environment. Specifically, the overexpression of the beta-S100 gene seems
      to affect the subjects' reactivity to the arousal-inducing properties of novel
      stimuli.

PMID- 7582814
TI  - Effect of syringeal denervation in the budgerigar (Melopsittacus undulatus): the
      role of the syrinx in call production.
AB  - In the budgerigar, the left and right tracheosyringeal nerves (ts) were sectioned
      both above and below the common anastomosis in order to assess the roles of the
      hypoglossal nuclei and syringeal muscle halves in the control of call production.
      Signal processing software was used to quantify changes in contact call
      fundamental frequency and duration, and similarity analysis for pre- and
      postsurgical contact calls was performed by means of spectrogram cross
      correlation. After resecting a portion of either the right or left ts nerve above
      the anastomosis (thereby eliminating the input from the ipsilateral half of the
      brainstem), contact call fundamental frequency decreased 40-50% on Day 1
      postsurgery, while call structure and duration remained largely unaffected.
      Fundamental frequency returned to normal within 4-7 days after surgery. In
      contrast, nerve sectioning below the anastomosis on either side of the syrinx
      (thereby eliminating input to the ipsilateral half of the syringeal muscles)
      resulted in moderately noisy harsh-sounding calls with little change in temporal
      characteristics. Thus, budgerigars differ from many oscines studied to date in
      that they do not demonstrate laterality in vocal control at the level of the
      syrinx. Vocalizations produced by birds after bilateral syringeal denervation
      were abnormal, consisting entirely of broadband harmonic sounds with very low
      fundamental frequencies (i.e., less than 900 Hz) and poor frequency modulation.
      In contrast, individual call durations, as well as the rhythm and patterning of
      vocalizations resembling warble song, were remarkably similar to presurgical
      recordings after both unilateral and bilateral ts nerve resection.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582815
TI  - Neurosteroids affect spatial/reference, working, and long-term memory of female
      rats.
AB  - Female rats take longer to acquire a spatial task during behavioral estrus, when
      GABA-active progesterone and metabolites are elevated. Whether neurosteroids and
      neuroactive steroids (neuro(active) steroids), which can act at GABA receptor
      complexes (GBRs), have activational effects on spatial/reference, working, and
      long-term memory was investigated. In Experiment 1, ovariectomized Long-Evans
      rats (N = 107) received oil vehicle or one of six neuro(active) steroids, with
      varying GBR efficacy (greatest to least efficacious: 5 alpha-pregnan-3 alpha-ol
      20-one (THP), 5 alpha-pregnan-3 alpha-ol-11,20-dione, 4-pregnen-3,20-dione 17
      alpha-hydroxyprogesterone, 5-pregnen-3 beta-ol-20-one sulfate, and 5-androstan-3
      beta-ol-17-one sulfate (DHEAS). Following neuro(active) steroid (3.2 or 6.4
      mg/kg) or vehicle sc, rats were tested in a Morris water maze, the following week
      in a Y maze, and then in an open field. Neuro(active) steroid, but not vehicle,
      animals had decreased distances to the hidden water maze platform. THP (3.2 and
      6.4 mg/kg) animals were faster to find this platform than vehicle animals. In the
      Y maze, 3.2 mg/kg THP increased percentage correct, but 6.4 mg/kg THP increased
      latencies to the goal box. DHEAS had the opposite effect, with 3.2 mg/kg
      increasing latencies to the goal box, while 6.4 mg/kg increased percentage
      correct. In Experiment 2, N = 75 ovariectomized rats were icv implanted with one
      of the neuro(active)steroids or cholesterol vehicle and then tested for
      spatial/reference memory, working and long-term memory, and motoricity/anxiolysis
      as in Experiment 1. DHEAS implants decreased, while THP increased, latencies and
      distances to the hidden platform in the Morris water maze. In the Y maze, THP
      increased latencies and decreased percentage correct, but DHEAS increased the
      likelihood of correct choice. Open field behavior of animals administered the
      various neuro(active) steroids (sc or icv) was not different. Thus, of the
      neuro(active) steroids examined, the neurosteroids THP and DHEAS had the most
      pronounced activational affects on spatial/reference, working, and long-term
      memory, independent of motoricity.

PMID- 7582817
TI  - Enhancement of antibody production by a learning paradigm.
AB  - The experiments described here show that production of serum antibody to a
      defined protein antigen (hen egg-white lysozyme) can be elicited by classical
      Pavlovian conditioning in Wistar rats. Reexposure of animals to a gustatory
      conditioned stimulus that had previously been paired with antigen induces a
      reliable increase in antibody production. This conditioned production of
      antibodies of IgM and IgG isotypes is similar to that found in secondary
      responses elicited by reinjection of antigen. These findings demonstrate that the
      immune system can be stimulated to produce apparently normal antibody responses
      by a simple behavioral paradigm.

PMID- 7582818
TI  - Inhibitors of cAMP-dependent protein kinase impair long-term memory formation in
      day-old chicks.
AB  - There is substantial evidence that protein kinases, through the phosphorylation
      of substrate proteins, play a significant role in information processing in the
      brain, including processes underlying memory formation. Inhibition of the
      activity of the cyclic-adenosine monophosphate-dependent protein kinase A by the
      highly specific inhibitor, halofantrine, resulted in impairment of memory
      formation in day-old chicks trained on a single-trial passive avoidance task. A
      dose of 9.6 ng/chick halofantrine induced amnesia at the beginning of a protein
      synthesis-dependent long-term memory stage, the last of three stages of memory
      postulated to underly memory formation in the chick following passive avoidance
      learning. The concentration of halofantrine required for 50% inhibition of chick
      brain protein kinase A was found to be similar to that observed for bovine heart
      and rat liver. The amnestic effect of halofantrine is tentatively attributed to
      interference with de novo protein synthesis necessary for long-term memory
      consolidation. Neither anthraquinone nor the anthraquinone derivative
      anthraflavic acid, which have little effect on protein kinase A activity,
      affected memory retention. On the other hand, two other anthraquinone
      derivatives, chrysophanic acid and purpurin, which inhibit PKA activity, at doses
      of 0.25 and 0.5 ng/chick also yielded retention deficits. In these cases,
      however, retention losses occurred earlier than observed with halofantrine, at
      about 30 min post-training. The earlier effects of these inhibitors may be due to
      the additional inhibitory action of these compounds on protein kinase C activity,
      which has been demonstrated in previous studies to be implicated, possibly
      through phosphorylation of the GAP43 phosphoprotein, in memory processing in the
      stage of memory immediately preceding the protein synthesis-dependent long-term
      stage.

PMID- 7582819
TI  - The effects of ascorbic acid and oxiracetam on scopolamine-induced amnesia in a
      habituation test in aged mice.
AB  - The effects of a nootropic drug, oxiracetam (50-100-200 mg/kg ip), and a potent
      antioxidant agent, ascorbic acid (62.5-125-250 mg/kg ip), administered alone or
      in combination, were investigated on scopolamine-induced amnesia in a mouse
      habituation test. The light-dark aversion test was selected and was carried out
      in aged mice. Habituation to the test box occurred over a 3-day period, control
      mice showing a significant between-day increase in the time spent in the dark
      box, but not in the number of transitions. On Day 4, following post-trial
      administration over a 3-day period of oxiracetam (50-100 and 200 mg/kg ip) or
      ascorbic acid (62.5-125 and 250 mg/kg ip), a significant between-day increase in
      the time spent in the black area, but not in the number of transitions, was
      found. The combination of oxiracetam (100 mg/kg ip) with ascorbic acid (125 mg/kg
      ip) produced a similar pattern of results. The acute administration of
      scopolamine (0.25 mg/kg ip) to mice treated over a 3-day period with vehicle
      disrupted the habituation response. In mice that had received the 3-day treatment
      with oxiracetam or ascorbic acid or its combination, scopolamine failed to alter
      significantly the learning pattern. In conclusion, these data demonstrate that
      ascorbic acid, alone or in combination with oxiracetam, may prevent
      experimentally induced amnesia in aged mice.

PMID- 7582820
TI  - Latent inhibition in conditioned taste aversion: the roles of stimulus frequency
      and duration and the amount of fluid ingested during preexposure.
AB  - Two experiments examined the effects of total stimulus preexposure on latent
      inhibition (LI) in a conditioned taste aversion procedure with rats. Experiment 1
      varied the frequency and duration of saccharin preexposures. LI was an increasing
      function of the product of frequency x duration. Experiment 2 kept saccharin
      exposure time constant but varied the amount of saccharin consumed by
      manipulating number of hours of fluid deprivation prior to exposure. Deprivation
      schedule conditions affected the amounts consumed which, in turn, modulated LI
      magnitude, at least with a 1-day acquisition-test interval, as in Experiment 1.
      The data clearly indicate that LI is a function of total amount of contact with
      the preexposed saccharin solution. In addition, half of the subjects in
      Experiment 2 were tested 21 days after the conditioning event. LI was not present
      in any group tested at this interval. These data were discussed in regard to the
      controversy regarding whether LI represents a failure to acquire the CS-US
      association or a failure to retrieve that association.

PMID- 7582816
TI  - A visuospatial dysfunction following posterior cortex injury is attenuated by
      postinjury administration of the ACTH4-9 analog ORG 2766.
AB  - Rats were trained in a Y-shaped water maze to discriminate a light gray from a
      medium gray visual stimulus. The latter stimulus card cued the location of a
      nonvisible escape platform. The animals received either a sham operation or a
      large ablation in the posterior neocortex, and osmotic minipumps were implanted
      subcutaneously in the animal's back. The pumps chronically administered either
      saline or ORG 2766 at a rate of 0, 1, or 10 micrograms per 24 h for 14 days while
      the animals recovered in individual rat cages. Four weeks after surgery retention
      of the discrimination was tested and, for those reattaining criterion,
      transposition of the habit to a pairing of the medium gray card with a black
      stimulus card was assessed. Animals treated with 10 micrograms ORG 2766
      reattained criterion on the original discrimination more rapidly than did animals
      treated with 0 or 1 microgram. Neither the lesion nor the drug resulted in
      consistent influences upon transposition. There was no evidence that the drug
      protected neurons within the dorsal lateral geniculate nuclei. Postinjury
      treatment with some doses of ORG 2766 can attenuate the severity of some
      dysfunctions that accompany neurotrauma by influencing the development of
      behavioral compensation.

PMID- 7582822
TI  - The memory enhancing effects of cholecystokinin octapeptide are dependent on an
      intact stria terminalis.
AB  - Cholecystokinin is a gastrointestinal peptide which is released from the duodenum
      during eating. Cholecystokinin octapeptide (CCK-8) has been found to improve
      retention when administered intraperitoneally in intact mice but not in
      vagotomized mice. This suggested that CCK-8 improves retention by stimulating
      vagal afferents to the nucleus of the solitary tract in the brainstem. In this
      study, we tested whether nerve fibers in the stria terminalis which project from
      the NTS to the amygdala need to be intact for CCK-8 to enhance retention. Three
      groups of mice were used: nonoperated, bilateral cortical control lesioned, and
      bilateral stria terminalis lesioned. The lesions were performed 1 week prior to
      footshock avoidance training in a T-maze. Saline, CCK-8 (0.5 microgram/kg, ip),
      epinephrine (100 micrograms/kg, sc), or arecoline (1.5 mg/kg, sc) were
      administered immediately after training. Retention was tested 1 week later.
      Neither bilateral stria terminalis lesions nor cortical control lesions
      significantly altered acquisition of the task compared to the nonoperated group.
      Whether the groups received a saline injection after training or received no
      injection did not affect retention test performance. CCK-8 and epinephrine
      enhanced retention in the mice with cortical lesions but not in mice with stria
      terminalis lesions. Arecoline enhanced retention in both groups. Possible
      pathways and neurotransmitters mediating the effect are discussed.

PMID- 7582821
TI  - Morphine-induced deficits in sleep patterns: attenuation by glucose.
AB  - Morphine effects on many neural and behavioral measures, including tests of
      learning and memory, are attenuated by increased circulating glucose levels.
      Using systemic injections, we investigated the ability of glucose to attenuate
      sleep deficits induced by morphine administration in the rat. Morphine at 1 mg/kg
      produced a moderate decrease in slow wave sleep which was prevented by
      concomitant administration of 100 mg/kg of glucose. A higher dose of morphine (10
      mg/kg) severely delayed the onset of both slow wave sleep and REM sleep. These
      delays were attenuated by concurrent administration of 250 mg/kg of glucose.
      Thus, glucose reversals of morphine effects are also extended to measures of
      sleep.

PMID- 7582823
TI  - Age-related changes in plasma catecholamine and glucose responses of F-344 rats
      to a single footshock as used in inhibitory avoidance training.
AB  - Young adult (3 months) and aged (22 months) Fischer 344 male rats were prepared
      with chronic tail artery catheters. Two days after surgery, rats were transferred
      to a test chamber and exposed to a single footshock (0, 0.25, 0.50, or 1.0 mA for
      1 s). Blood samples were obtained from each rat under basal conditions and at
      timed intervals after exposure to footshock. Basal plasma levels of
      norepinephrine (NE) and epinephrine (EPI) were similar for 3- and 22-month-old
      rats. In contrast, plasma glucose (GLU) levels were significantly lower in aged
      rats compared to young adults. Increments in plasma levels of EPI were greater in
      aged rats compared to young adult controls following transfer of rats to the test
      chamber. In addition, aged rats had potentiated plasma EPI responses to
      footshock. Finally, aged rats had greater plasma levels of both catecholamines up
      to 5 min after a single training footshock compared to young adult controls.
      However, the increased responsiveness of EPI in aged rats was not accompanied by
      proportionate increases in plasma GLU levels, i.e., the EPI-GLU relationship was
      uncoupled in aged rats. These findings point to dramatic differences between
      young adult and aged rats in their plasma EPI responses to inhibitory avoidance
      training. Age-related increases in EPI secreted from the adrenal medulla,
      together with decreased blood GLU responses, may contribute in part to age
      related deficits in memory modulatory processes.

PMID- 7582828
TI  - Malignant melanoma: treatment in evolution.

PMID- 7582824
TI  - Influence of separate and combined septal and amygdala lesions on memory,
      acoustic startle, anxiety, and locomotor activity in rats.
AB  - The septohippocampal system and the amygdala have been implicated in cognitive
      and emotional processes. A series of experiments was conducted to examine the
      effects of separate and combined lesions of these areas on a variety of
      behaviors, including: startle responses to acoustic stimuli; sensory gating,
      using prepulse inhibition of acoustic startle; anxiety, using the elevated plus
      maze; locomotor activity in an open field; and memory, using both a spatial
      discrimination version of the Morris water maze and the inhibitory (passive)
      avoidance test. Both septal and fimbria-fornix lesions markedly impaired the
      acquisition of spatial information in the water maze, had anxiolytic-like effects
      in the elevated plus-maze, increased reactivity to footshock, and had marginal
      effects on prepulse inhibition and baseline startle. Septal and fimbria-fornix
      lesions also increased locomotor activity in the later stages of a session of
      open field exploration, but only septal lesions produced "freezing" during the
      early portion of this session and during inhibitory avoidance training. Amygdala
      lesions markedly impaired prepulse inhibition of acoustic startle. Amygdala
      lesions also attenuated the effects of septal lesions on freezing in the open
      field and on footshock reactivity, but did not affect the anxiolytic-like effects
      or hyperactivity associated with septal lesions. Amygdala lesions by themselves
      had no significant effect on water maze performance, but significantly
      potentiated the effects of septal lesions. These results suggest that there are
      dissociations between the effects of septal and fimbria-fornix lesions and that
      the interactions between the amygdala and septum in cognitive and emotional
      processes are task dependent.

PMID- 7582826
TI  - A simple and rapid test of sensorimotor function in the aged rat.
AB  - A total of 107 Fischer 344 rats (male and female, 2 to 29 months old) were tested
      on three tasks designed to measure sensorimotor function. In the first task, a
      new test of sensorimotor function, animals were required to maintain their
      balance on a stationary inclined Plexiglas plane for 5 s. Performance was
      evaluated with a series of increasing angles ranging from 25 degrees to 50
      degrees in 1 degree increments (four trials/angle). The animals were also
      evaluated on two common tests of sensorimotor function: suspension from a wire by
      the forepaws and traversing a narrow, horizontal bar (three trials each). Age
      effects were significant (p < .043 to p < .0001) for each of the 11 dependent
      measures (first fall angle, threshold angle, and total falls for the inclined
      plane, and first, best, mean, and median latencies to fall for the remaining two
      tests). No relationship was observed between performance, sex, and body weight.
      Coefficients of variation differed between tests, with the inclined plane being
      the least variable and the horizontal bar the most. Importantly, the inclined
      plane was least likely to violate the ANOVA assumption of homogeneity of
      variance, a problem often encountered when measuring age-related variables. Since
      the inclined plane test has a relatively low degree of variability, and since the
      between-group variation is homogeneous, it should serve as both a useful and
      robust test for sensorimotor function in the aged rat.

PMID- 7582827
TI  - Chronic sodium azide treatment decreases membrane-bound protein kinase C activity
      in the rat hippocampus.
AB  - Chronic administration of sodium azide in rats inhibits cytochrome oxidase and
      produces learning and memory deficits. The present experiment tested the
      hypothesis that chronic sodium azide treatment might also alter protein kinase C
      activation. Continuous infusion of sodium azide (400 micrograms/h, sc) in rats
      for 2 weeks significantly decreases membrane-bound protein kinase C in
      hippocampus, but not frontal cortex, temporal cortex, or cerebellum. Since
      protein kinase C activation is correlated with hippocampus-dependent learning,
      these results suggest a possible biochemical mechanism for azide-induced
      impairment of learning.

PMID- 7582825
TI  - Neuroanatomical and functional specificity of the basolateral amygdaloid nucleus
      in taste-potentiated odor aversion.
AB  - The present study aimed at documenting the neurobiological substrate of taste
      potentiated odor aversion (TPOA) in the rat. The role of several temporal lobe
      structures in discriminative TPOA learning was questioned. The effects of
      excitotoxic lesions (ibotenate) of the basolateral amygdaloid nucleus, the
      central amygdaloid nucleus, the caudate putamen nucleus, and aspirative lesion of
      the entorhinal cortex were studied. The results show that only basolateral
      amygdaloid nucleus (ABL) damage impaired TPOA. This effect was selective of TPOA,
      since it spared conditioned taste aversion (CTA) and olfactory perception. In
      order to find out which process in TPOA requires normal functioning of the ABL,
      the effects of microinjections of a GABAA agonist (muscimol) into the ABL at
      various stages of the experiment were examined. The results show that application
      of muscimol during the acquisition, before or after the presentation of the odor
      taste stimulus, impaired TPOA without affecting CTA. Contrastingly, application
      of muscimol before the test impaired neither TPOA nor CTA. These results suggest
      that ABL is involved in the acquisition but not in the retrieval of TPOA. The
      efficacy of muscimol microinjected after the presentation of the odor-taste
      stimulus further suggests that the deficit is not due to a sensory impairment but
      rather to the disruption of a memory process, critical for TPOA.

PMID- 7582829
TI  - Stump the experts. Case. Granular-cell tumor.

PMID- 7582830
TI  - Management of stage I malignant melanoma.
AB  - BACKGROUND: Because of the rising incidence of melanoma, dermatologists are
      increasingly responsible for diagnosing and managing patients with this cutaneous
      malignancy. Fortunately, with the increased awareness and emphasis on early
      detection, most patients will present with tumors that have not yet spread beyond
      their primary focus in the skin (ie, Stage I). Dermatologists must, therefore, be
      fully versed in the diagnosis and management of Stage I melanoma. OBJECTIVE: This
      review article focuses on the most important issues related to the diagnosis and
      management of Stage I melanoma. An emphasis will be placed on surgical
      management. RESULTS: The mainstay of therapy for most patients with Stage I
      melanoma is surgery. The important principles of diagnostic biopsy and surgical
      excision will be discussed. There are several additional modalities that may be
      useful as adjuvants to surgical therapy or as primary therapy in situations when
      surgery is not feasible. Those include elective lymph node dissection,
      hyperthermic isolation limb perfusion, radiotherapy, cryotherapy, chemotherapy,
      and immunotherapy. These will all be reviewed. CONCLUSIONS: With a thorough
      understanding of the important principles and controversies related to the
      management of Stage I melanoma, dermatologists can effectively manage the growing
      number of patients with this malignancy.

PMID- 7582832
TI  - Silicone gel sheeting for the prevention and management of evolving hypertrophic
      and keloid scars.
AB  - BACKGROUND: Hypertrophic scars and keloids remain a problem for surgeons. Topical
      and intralesional corticosteroids, positive pressure dressings, cryotherapy, and
      laser therapy are helpful but not uniformly successful. OBJECTIVE: To document
      the effectiveness of silicone gel sheeting in the prevention and/or reduction of
      evolving hypertrophic scars and keloids. METHODS: Silicone gel sheeting was
      placed over evolving scars in 20 cases. The dressing was worn for at least 12
      hours a day. Biopsies were examined for the presence of silica in the tissue.
      RESULTS: Lesions improved during the treatment period in 85% of the cases. The
      mechanisms of action are unknown. Positive pressure was not necessary. No silica
      from the dressing was found at the wound site. CONCLUSION: Daily treatments with
      silicone gel sheeting should begin as soon as an itchy red streak develops in a
      maturing wound. The dressing is effective in reducing the bulk of these lesions.

PMID- 7582831
TI  - Skin resurfacing of fine to deep rhytides using a char-free carbon dioxide laser
      in 47 patients.
AB  - BACKGROUND: Recent advances in carbon dioxide (CO2) laser technology have
      resulted in the development of lasers that can precisely remove thin layers of
      skin with minimal thermal damage to the surrounding tissue. These lasers rely on
      rapid pulsing or scanning of the laser beam. The effects of these lasers are
      predictable and reproducible, making them ideal for skin resurfacing. Clinical
      results have been promising, however, to date, no published series exist.
      OBJECTIVE: To evaluate the effectiveness and side effect profile of laser
      resurfacing utilizing a CO2 laser with a scanning device, and make
      recommendations for patient selection and treatment protocol. METHODS: Patients
      with perioral, periorbital, and glabellar rhytides were treated with a CO2 laser
      with a scanning device. Utilizing chart review and photographic evaluation,
      patients treated between November 1994 and April 1995 were retrospectively
      evaluated for effectiveness of therapy, healing time, and complication rates.
      RESULTS: A total of 47 patients were evaluated. Photographic evaluation or chart
      review revealed good to excellent cosmetic results in all anatomic areas studied.
      All patients experienced posttreatment erythema lasting 1-6 months. Other minor
      complications were limited to contact dermatitis to topical preparations,
      transient postinflammatory hyperpigmentation, and milia formation. One patient
      experienced a primary herpes simplex virus infection during reepithelialization
      and required intravenous therapy. Minor focal atrophy was seen in one patient. No
      hypertrophic scarring or permanent pigmentation changes were seen. CONCLUSIONS: A
      CO2 laser system with a scanning beam can effectively and safely improve or
      remove glabellar, perioral, and periorbital rhytides.

PMID- 7582833
TI  - The use of full-thickness skin grafts for the repair of defects on the dorsal
      hand and digits.
AB  - BACKGROUND: The hand is a complex part of the human body and plays an important
      role in our everyday lives. It is critical to preserve manual function when
      repairing surgical defects on the dorsum of the hand and digits. OBJECTIVE: To
      demonstrate the effectiveness of the full-thickness skin graft (FTSG) in the
      repair of surgical defects on the dorsum of the hand and digits. METHODS: Through
      a retrospective review of photographic and written records and person-to-person
      interviews, the authors evaluated 19 patients who underwent FTSG repair of 21
      defects on the dorsum of the hand and digits after Mohs micrographic surgery.
      RESULTS: In all cases, the FTSG was durable, yielded good cosmetic results, and
      maintained normal function of the hand. CONCLUSION: The FTSG is a good option for
      repairing surgical defects on the dorsum of the hand and digits.

PMID- 7582834
TI  - Nonmelanoma skin cancers in association with seborrheic keratoses.
      Clinicopathologic correlations.
AB  - BACKGROUND: Seborrheic keratoses (SKs) can be seen in association with cancers.
      OBJECTIVE: Our study was designed to demonstrate the occurrence of concomitant
      SKs and nonmelanoma skin cancers, as well as to correlate their histological
      types and clinical locations. The study was not intended to be an epidemiologic
      survey. METHODS: We prospectively collected 108 completely excised SKs, examined
      them microscopically, categorized them, and correlated the clinical site,
      histological type, and determined the incidence of concomitant malignancy.
      RESULTS: Of the 108 SKs studied, 71 were acanthotic, 27 hyperkeratotic, and 10
      reticulated. The incidence of associated nonmelanoma cancers was 4.6%. All
      malignancies were squamous cell carcinomas and were on sun-exposed skin. Three of
      the five malignancies arose in conjunction with reticulated SKs. CONCLUSIONS: The
      incidence of nonmelanoma skin cancer in association with SKs may be greater than
      previously reported, particularly in SKs situated on photo damaged skin and of
      the reticulated type. SKs that have undergone recent growth or other clinical
      change should be biopsied and all SKs that are removed should be examined
      histologically.

PMID- 7582835
TI  - A concentric method for mini-micrografting extensively bald patients.
AB  - BACKGROUND: A concentric method for mini-micrografting extensively bald patients
      is described. OBJECTIVE: To demonstrate a method that effectively treats those
      extensively bald patients who wish to forgo any type of alopecia-reducing
      procedure posteriorly. METHOD: Initially the hairline is developed. Then the
      remaining posterior area of alopecia is gradually infringed upon in a concentric
      fashion. RESULTS: Excellent results are accomplished with this method and, most
      importantly, the patient looks normal at any point during the treatments. If
      donor hair becomes depleted or the patient wishes no further treatments, he/she
      is left with a normal appearance. CONCLUSION: The method of performing mini
      micrografts, starting from the front and moving posteriorly in a progressively
      concentric fashion, creates a very natural result at almost all phases of the
      surgical hair restoration.

PMID- 7582836
TI  - The chondrocutaneous helical rim advancement flap of Antia and Buch.
AB  - BACKGROUND: The cutaneous surgeon commonly encounters defects of the helix, as 2
      4% of all skin cancers occur at this site. OBJECTIVE: We report our experience
      with 47 patients using the chondrocutaneous helical rim advancement flap of Antia
      and Buch. METHODS: Incisions are made from the defect inferiorly into the lobule
      and, when necessary, superiorly along the helical sulcus into the helical crus.
      The postauricular skin is extensively undermined to allow maximal movement of the
      resulting broadbased, well-vascularized flap(s). RESULTS: We experienced very
      favorable results using this technique with our patients. No necrosis due to
      ischemia occurred in any of our cases. Hematomas formed postoperatively in two
      patients, but healing proceeded uneventfully after removal of coagulated blood.
      CONCLUSION: This technique is an excellent method of repairing many defects of
      the helical rim. Its advantages include technical simplicity, little risk of tip
      necrosis, patient convenience, and superior cosmesis.

PMID- 7582837
TI  - Intraoperative radiation therapy and Mohs micrographic surgery on an outpatient
      basis.
AB  - BACKGROUND: Intraoperative radiation therapy (IORT) is used to deliver
      therapeutic doses of radiation to a surgically exposed tumor or tumor bed while
      minimizing the radiation dose to adjacent normal tissue. It is traditionally
      given with the patient under general anesthesia. OBJECTIVE: To report a case of a
      recurrent squamous cell carcinoma treated with Mohs micrographic surgery and IORT
      on an outpatient basis. METHODS: Mohs surgery was used to clear the tumor in all
      fields except for the area of the spinal accessory nerve, which was preserved.
      IORT was then delivered to the area of nerve with possible residual tumor.
      RESULTS: The patient remains clinically tumor free 42 months posttreatment. There
      were no complications. CONCLUSION: Intraoperative radiation therapy can be
      effectively used in the outpatient setting as an adjunctive therapy after Mohs
      micrographic surgery.

PMID- 7582838
TI  - The role of selective lymphadenectomy in the management of patients with
      malignant melanoma.
AB  - BACKGROUND: A novel surgical technique based on selective lymphadenectomy was
      used to stage 132 patients with intermediate and thick cutaneous malignant
      melanoma. Preoperative and intraoperative lymph node mapping techniques were used
      to ascertain regional lymph node basins at risk for metastasis, and to identify
      the first node(s) the afferent lymphatics encounter in the basin, defined as the
      "sentinel" node(s). It has been shown that the histology of the sentinel node
      reflects the histology of the rest of the nodal bain, and according to
      preliminary studies using this technique, the likelihood of bypassing the
      sentinel node(s) to "higher" level nodes is less than 2%. Epidemiologic studies
      indicate that the long-term survival of patients with melanomas of intermediate
      thickness or greater is significantly compromised if regional lymph nodes are
      involved. Yet, the utility of performing lymph node dissections for the purposes
      of staging only is controversial, not only because of the morbidity and expense
      of the procedure, but the lack of proven survival benefit. OBJECTIVE: In the
      present study, we performed preoperative and intraoperative lymphatic mapping,
      harvested clinically normal sentinel nodes, and examined them for micrometastasis
      by light microscopy. Both conventional stains and immunocytochemistry for S-100
      protein and HMB-45 antibodies were performed, and only those patients with
      documented micrometastasis received complete lymph node dissections. RESULTS: The
      sentinel node(s) was identified in each of the patients. Micrometastatic disease
      was detected in 31 (23%) of the patients by selective lymphadenectomy, and the
      sentinel node(s) was the only node involved in 83% of the cases upon subsequent
      complete nodal dissection. CONCLUSION: Our preliminary results suggest that
      selective lymphadenectomy following lymphatic mapping is an effective procedure
      for staging melanoma patients with lesions of intermediate thickness or greater.
      Our results indicate that sentinel lymph nodes may be successfully identified and
      harvested in the majority of patients, and that they may be examined for the
      first evidence of micrometastasis without the need of a complete nodal
      dissection. Information as to whether micrometastases are present in the sentinel
      node would be valuable in staging patients, and identifying candidates for
      complete nodal dissections. We are participating in a National Cancer Institute
      sponsored multicenter trial to ascertain whether this surgical approach can
      impact on the recurrence rate and survival of patients with stage 1 and 2
      melanoma.

PMID- 7582840
TI  - A rapid micrograft implantation technique.
AB  - OBJECTIVE: A rapid and simple method for the implantation of micrografts is
      presented. METHODS: A 14-gauge needle is used to deliver the micrograft to the
      recipient hole created by the needle. Jeweler's forceps are used to seat the
      graft once it is in place. RESULTS: The needle-guided implantation technique
      described here is a fast and effective method for insertion of one- or two-hair
      grafts at the frontal hairline or over extensive areas of hair loss. CONCLUSION:
      The technique described can be readily learned and produces excellent cosmetic
      results.

PMID- 7582841
TI  - Removal of cutaneous pigmented lesions with Q-switched lasers.

PMID- 7582839
TI  - Onychomatricoma.
AB  - BACKGROUND: Onychomatricoma is a rare benign tumor originating in the nail
      matrix. Only eight cases have been reported until now. OBJECTIVE: The clinical
      and histopathological features of this recently reported tumor will be described
      and its differential diagnoses outlined. A typical case of onychomatricoma is
      described in a 62-year-old white man. RESULTS: Clinically, onychomatricoma is
      characterized by: 1) a yellowish discoloration of a longitudinal segment of the
      nail plate with small splinter hemorrhages within the proximal portion of the
      nail; 2) a thickening with increased transversal curvature of the involved nail
      plate positively corresponding with the yellow discoloration; and 3) a matrix
      tumor consisting of multiple fine filiform projections that extend into the
      thickened nail plate. The treatment of onychomatricoma is complete excision of
      the tumor. CONCLUSION: Onychomatricoma is a new entity with clinical and
      histopathological features that are characteristic enough to make the correct
      diagnosis.

PMID- 7582842
TI  - Does the presence of atypical mitotic figures in keratoacanthomas indicate a more
      aggressive biologic behavior?

PMID- 7582843
TI  - A persistent dermal nodule in an African-American patient.

PMID- 7582844
TI  - Disseminated cutaneous Cryptococcus clinically mimicking basal cell carcinoma.

PMID- 7582845
TI  - Ruby laser treatment of melasma and postinflammatory hyperpigmentation.

PMID- 7582846
TI  - Surgical instruments: extensions of the brain, not the hand. A thought and
      philosophy of the ISDS' Inaugural Traveling Chair of Dermatologic Surgery.
      International Society for Dermatologic Surgery.

PMID- 7582850
TI  - The diurnal rhythm of hepatotoxic action of chloroform.
AB  - Mice were administered with chloroform at 10 a.m., 2 p.m. and 6 p.m. and the
      signs of hepatotoxicity were measured 18 or 24 hrs later. The levels of alanine
      aminotransferase (ALT) in serum, and malondialdehyde (MDA) in the liver were
      higher after the evening administration compared to the morning one. The
      decrements of reduced glutathione (GSH) levels in the liver followed a similar
      pattern. It is concluded that the susceptibility of mice to the toxic effect of
      chloroform follows a circadian rhythm.

PMID- 7582849
TI  - Activities of acetylcholinesterase and NA+, K+ -ATP-ase in human erythrocytes
      after ethanol consumption.
AB  - The influence of ethanol consumption on acetylcholinesterase (AchE) and Na+, K+ 
      ATP-ase activities was examined in 14 healthy volunteers after 30 minutes of
      ethanol treatment at a dose 0.6 g/kg of body weight. It was observed that the
      activity of both enzymes decreased. The activity of AchE was significantly lower,
      and that of Na+, K+ -ATP-ase tended to be lower, but the difference was not
      significant. In vitro experiments showed that ethanol inhibited the AchE and N+,
      K+ -ATP-ase activities immediately and in proportion to the concentration of
      ethanol used.

PMID- 7582847
TI  - Postoperative removal of pressure by eyeglasses.

PMID- 7582851
TI  - DNA repair synthesis induced by azo dyes in primary rat hepatocyte cultures using
      the bromodeoxyuridine density-shift method.
AB  - The genotoxic activity of the benzeneamine-derived azo dyes, Disperse Red 54 (DR
      54), Direct Red 81 (DR 81) and Direct Black 19:1 (DB 19:1) was studied in the in
      vitro DNA repair assay in primary rat hepatocyte cultures. Hepatocytes were
      isolated, cultured and treated with the azo dyes, bromodeoxyuridine and [3H]
      cytidine. DNA repair synthesis was determined as an incorporation of [3H]
      cytidine into unreplicated DNA strands using the bromodeoxyuridine density-shift
      method. Of the 3 azo dyes, only DR54 (monoazo dye) induced a weak DNA repair
      synthesis in rat hepatocytes in vitro. DR81 and DB 19:1 did not induce any
      concentration-related DNA repair synthesis expressed as cpm/micrograms DNA. The
      data suggest that the in vivo reduction of azo dyes is required for the
      genotoxicity of these azo dyes.

PMID- 7582852
TI  - Acute changes in the EEG of workers exposed to mixtures of organic solvents.
AB  - In a pilot study, 11 workers were exposed to mixtures of organic solvents during
      the cleaning of printing rolls. The exposure was considered as low to moderate.
      The "electroencephalogram (EEG)" was recorded before and after the cleaning. The
      spectral power was calculated by Fast Fourier Transformation in six frequency
      bands. After exposure the spectral power in particular increased in the alpha-1
      band and in the temporooccipital leads of the delta band in the closed-eye
      condition.

PMID- 7582853
TI  - Latex allergy.
AB  - Over the last ten years allergy to latex has become a serious, life-threatening
      medical problem. Exposure to latex may result in immediate hypersensitivity
      reactions such as urticaria, dyspnoe, rhinitis, angioedema and anaphylactic shock
      in sensitized individuals. People occupationally exposed to latex--health care
      and rubber industry workers and children suffering from spina bifida--are the
      most important risk groups. Clinical manifestations, immunological mechanisms,
      trials for identifying latex allergens and laboratory testing are reviewed here.
      Moreover, the authors present two cases of latex allergy diagnosed with the use
      of a nasal challenge test. 0.0005% latex solution (Stallergen) and latex extract
      prepared at the Clinic were used. Nasal washings were performed before, 30
      minutes, 3 and 24 hours after provocation. The test evaluation was based on
      changes in the number and type of cells present in the washings. As there is no
      laboratory test to be used in latex allergy diagnosis approved by the Food and
      Drug Administration (FDA) the nasal provocation test seems to be worthy of
      further investigation. Ways of reducing of the allergenicity of latex products
      and preventing hypersensitivity reactions are also presented.

PMID- 7582854
TI  - Recent trends and developments in occupational health policies and professional
      practices of company doctors. Current developments in the Federal Republic of
      Germany.
AB  - In Germany a comprehensive system of legislation and institutions for prevention
      of occupational diseases and accidents at work has been built up over more than
      100 years. The paper presents regulations and new initiatives in the field of
      occupational health and safety, undertaken in the country, known as the Act on
      Company Doctors and compares it with the EU recommendations.

PMID- 7582848
TI  - Diagnostic value of urine cytology and urine carcinoembryonic antigen (CEA) level
      in the distinction between bladder cancer and urinary tract infection.
AB  - In the retrospective investigation we estimated the CEA levels in urine and urine
      cytology in 293 patients with urinary bladder cancer (group I) and in 129
      patients with urinary tract infection (group II). An increased CEA level was
      found in 212 cases of bladder cancer and in 109 cases of urinary infection.
      Neoplastic cells in urine sediment were identified in 254 cases in the first
      group, while in the second, multiple inflammatory cells and pyuria were diagnosed
      in 55 and 56 cases, respectively. The combined examination (increased CEA level
      and/or positive cytology of the urine sediment) allowed for the diagnosis of
      neoplastic disease in 270 patients in the first group and infection diseases in
      123 patients in the second group. After surgical therapy an increased urine CEA
      level and neoplastic cells in the urine cytology were found in 1 case which was
      then confirmed histopathologically. In the group with urinary infection an
      increased CEA level in urine, after antiphlogistic therapy, was found in 5 cases,
      inflammatory cells in 12 cases, pyuria in 8 cases and suspect cells were found in
      6 cases in the group with urinary infection. In specimens from these cases, after
      electroresection, bladder cancer was diagnosed in 2, and cystitis cystica type
      changes in 2 cases.

PMID- 7582857
TI  - Effects of adrenochrome and epinephrine on human arterial endothelial cells in
      vitro.
AB  - The effects of adrenochrome and epinephrine were investigated in cultured human
      umbilical arterial endothelial cells. The cells were exposed to either
      adrenochrome or epinephrine at levels of 50 and 200 microM, respectively, up to
      24 hrs. At 3, 5, 7 and 24 hrs of the designed harvesting time, [3H]thymidine
      incorporation, protein content, [3H]cholesterol uptake, prostacyclin production
      and lipid peroxidation were measured. We found that adrenochrome at a level of
      200 microM inhibited [3H]thymidine incorporation, decreased protein content,
      stimulated [3H]cholesterol uptake, and decreased prostacyclin production after 3,
      5, 24 and 5 hrs of exposure, respectively, compared with control. It took 24 hrs
      however for epinephrine at a level of 200 microM to inhibit [3H]thymidine
      incorporation and prostacyclin production. When the concentration was reduced to
      50 microM, only adrenochrome inhibited [3H]thymidine incorporation after 24 hrs
      of treatment. Both adrenochrome and epinephrine had no effect on lipid
      peroxidation. We suggest that atherogenic changes found in severe hypertension
      may be due to abnormal high concentration of epinephrine, especially oxidized
      epinephrine, on endothelial cell functions, such as DNA synthesis, cholesterol
      uptake and prostacyclin production.

PMID- 7582855
TI  - Regulation of breathing in cases of acute carbon monoxide poisoning.
AB  - The contribution of the central and peripheral nervous system to the regulation
      of breathing in acute carbon monoxide poisoning was evaluated through the
      analysis of respiratory pattern parameters, mainly the values of tidal volume to
      the inspiratory flow (VT/T(in)--driving component), and the relation of
      inspiratory time to the total cycle time (T(in)/T(tot)--timing component). In the
      examination performed as soon as possible after poisoning, an increase in the
      value of the VT/T(in) parameter and a diminishing of T(in)/T(tot) value were
      noted. Lightly poisoned subjects showed higher dynamics of changes in the
      regulation of breathing than the medium and severely poisoned patients. Both
      respiratory pattern components, measured after treatment, were in the lightly
      poisoned group comparable to the healthy subjects, whereas in the medium and
      severely poisoned group the value of VT/T(in) was elevated, and the value of
      T(in)/T(tot) was lessened in comparison to the control counterpart. Both
      respiratory pattern components significantly correlated to the blood lactace
      level, and to the degree of poisoning estimated in a complex way.

PMID- 7582856
TI  - Effects of 2-deoxyglucose, a metabolic inhibitor, on spontaneous contraction and
      adrenoceptor responsiveness in cultured rat ventricular myocytes.
AB  - Although it is well known that myocardial ischemia induces the depletion of
      myocardial ATP and sustained myocardial dysfunction, the mechanisms causing
      impaired myocardial function have not been elucidated completely. To clarify the
      relationship between ATP depletion and myocardial contractility, we investigated
      the influence of myocardial ATP depletion on spontaneous beating in cultured rat
      ventricular myocytes. Furthermore, because catecholamines have been used to
      improve myocardial contraction in the ischemic heart, we attempted to determine
      whether the ATP depletion per se alters the contractile responses to alpha 1- and
      beta-adrenoceptor stimulation. After 24 hr of culture in the presence of a
      metabolic inhibitor, 2-deoxyglucose (2DG, 5mM), myocardial contractility
      decreased to 19% of the vehicle level, and returned to normal after the removal
      of 2DG. The beating rate did not show any alterations in the vehicle, in the
      presence of 2DG (2DG [+/+]) or after the removal of 2DG (2DG [+/-]).
      Norepinephrine (NE) caused significant decreases in beating rate and increases in
      contractility in all groups. Isoproterenol (ISP) caused significant increases in
      beating rate and contractility in all groups. In the 2DG (+/+) group, the
      contractility was significantly lower as compared to other groups during NE or
      ISP stimulation. However, the percent change of contractility was similar to
      those of other groups after NE or ISP stimulation in the 2DG (+/+) group. These
      results suggest that decreased myocardial ATP causes the decreased contractility
      and does not affect the alpha 1- or beta-adrenoceptor-mediated responses.

PMID- 7582859
TI  - In vivo disposition and in vitro metabolism of an anxiolytic compound, BMS
      184111, in rats.
AB  - Plasma concentrations of BMS-184111, an anxiolytic, were determined as a function
      of time following single intravenous, intraperitoneal and oral administrations.
      In order to assess the brain penetration of this compound, concentrations in
      whole brain samples were also determined in the intravenous leg of the study.
      Concentrations of BMS-184111 in plasma and brain homogenate samples were
      determined using an HPLC assay following liquid/liquid extraction. After
      intravenous administration, BMS-184111 was eliminated from plasma with a half
      life of about 3.6 hours. The brain/plasma AUC ratio for BMS-184111 concentration
      was 5.5, indicating effective penetration of the compound into the brain.
      Comparison of the plasma AUC values obtained following intravenous and
      intraperitoneal doses indicated that BMS-184111 was only 33% bioavailable after
      intraperitoneal administration, suggesting that the compound undergoes
      significant first-pass hepatic extraction. The oral bioavailability of BMS-184111
      was found to be 10% after administration of the free base and 23% after
      administration of the hydrochloride salt. These results suggest that BMS-184111
      undergoes incomplete GI absorption and/or intestinal metabolism in addition to
      first-pass hepatic extraction. The in vitro metabolism of BMS-184111 was studied
      using rat liver homogenate preparation (the 9000 g supernatant; S-9). Several of
      the metabolites thus generated were profiled using LC/MS and LC/MS/MS. Metabolism
      of BMS-184111 in rat liver S-9 occurs through hydroxylation, O-demethylation, and
      demethylenation.

PMID- 7582858
TI  - Myocardial toxicity of cyclosporin A: inhibition of calcium ATPase and nitric
      oxide synthase activities and attenuation by fructose-1,6-diphosphate in vitro.
AB  - Use of cyclosporin A (CsA) in transplantation medicine has been shown to cause a
      number of toxic cellular side effects, which has prompted a search for
      formulations that afford protection from these undesirable sequelae. Previously
      we demonstrated that fructose-1,6-diphosphate (FDP) can reverse a variety of
      toxic cellular effects that arise upon use of various chemical agents. The
      present studies were undertaken to study the effects of CsA on rat myocardial
      Ca2+, calmodulin (Cam)-dependent enzymes such as Ca2+ ATPase and nitric oxide
      synthase (NOS) and the role of FDP in attenuating these changes in vitro. Rat
      ventricular sarcoplasmic Ca2+ ATPase was studied by measuring the inorganic
      phosphorous liberated on ATP hydrolysis and rat heart 100,000 g fraction NOS
      activity by monitoring the formation of [3H]-citrulline in the presence of 10
      1000 microM CsA and 1000 microM CsA + 1000 microns FDP in vitro. CsA in all
      concentrations significantly (P < 0.001) inhibited both Ca2+ ATPase and NOS
      activities of rat myocardium and FDP at 1000 microM concentration completely
      reversed the 1000 microM CsA-inhibited Ca2+ ATPase and cNOS activities of rat
      myocardium. These data indicate that CsA may inhibit Ca2+ ATPase and NOS
      activities in the rat myocardium through interference with its Ca2+/Cam-mediated
      events and thus may cause myocardial toxicity. FDP may reverse these changes.

PMID- 7582861
TI  - Pharmacokinetic study of trimethadione and its metabolite in blood, liver and
      brain by microdialysis in conscious, unrestrained rats.
AB  - A microdialysis method has been developed in the past two decades to determine
      levels of drug and endogenous compounds in several organs under physiological
      conditions. In this study, we determined the pharmacokinetics of the model drug,
      trimethadione (TMO), and its only metabolite, dimethadione (DMO), in liver, blood
      and brain by the microdialysis method in freely-moving rats. Sampling times were
      extended up to 24 hours. The construction of a newly developed microdialysis
      probe for liver and blood is described. The elimination patterns of TMO in liver,
      blood and brain dialyzates were almost identical and the calculated t1/2 was
      approximately 3 hr in each sample. However, in brain, tmax was delayed compared
      with the others while the relative concentration of DMO (AUC0-24h) was lower in
      brain compared with liver and blood. These studies suggest that this concurrent
      and successive microdialysis sampling method will not only be a useful tool for
      pharmacokinetic and drug metabolism studies in the organs of small animals but
      will also decrease the number of experimental animals needed for a study.

PMID- 7582860
TI  - Daunomycin inhibits insulin-like growth factor I-dependent protein tyrosine
      phosphorylation.
AB  - The effect of the antitumor antibiotic daunomycin (DN) was studied on insulin
      like growth factor I (IGF-I)-dependent protein tyrosine phosphorylation. DN was
      found to inhibit IGF-I-dependent phosphorylation of the artificial substrate
      poly(Glu:Tyr)4:1 by intrinsic IGF-I receptor kinase either from mouse cerebellum
      or from rat spinal cord. IGF-I-dependent autophosphorylation of the IGF-I
      receptor was also inhibited as a function of DN concentration (10-100 microM).
      However, DN at 200 microM concentration had minimal effect on protein kinase C
      dependent phosphorylation. The IGF-I-dependent protein tyrosine phosphorylation
      of endogenous proteins of the rat spinal cord was also inhibited by 50 microM DN.
      The altered IGF-I-dependent protein tyrosine phosphorylation by DN may partially
      explain its mechanism of action as an antitumor agent. These observations may
      also explain the neurotoxic effects of DN.

PMID- 7582862
TI  - Effects of 4'-chlordiazepam on glycemia and serum lipids in hyperlipidemic rats:
      interactions with PK 11195 and flumazenil.
AB  - In rats rendered hyperlipidemic by the interperitoneal injection of Triton WR
      1339, the administration of 4'-chlorodiazepam, a selective agonist of the
      peripheral type of benzodiazepine (BZO) receptors evoked significant reductions
      of serum lipids. PK 11195, a specific antagonist of these receptors, partially
      inhibited these effects. Flumazenil, a selective antagonist of the central BZD
      receptors, enhanced the lipid lowering activity of 4'-chlorodiazepam.

PMID- 7582863
TI  - Rapid fibrinogen determination with the prothrombin time using a
      potentiophotometer.
AB  - The potentiophotometer (PTPH) is a spectrophotometric device that embodies the
      electrical, analog solution to Beer's Law. The output of the instrument gives,
      directly and simultaneously, the concentration of the substance being measured.
      The PTPH has been applied to the manual determination of fibrinogen (FBG) with
      the same thrombopalstin injection as the prothrombin time (PT). We have now semi
      automated and computerized the PTPH to constitute the coagulation instrument
      named POTENS+. POTENS+ determines the FBG rapidly, within approximately three to
      twenty seconds after the PT. With POTENS+, precision, linearity and reference
      range will be given for its FBG method. The accuracy of POTENS+ will be assessed
      by comparing it with both automated FBG methods on the MLA Electra 1000C
      Coagulation Timer. Of these two methods, the automated Clauss method is used as
      the reference method.

PMID- 7582865
TI  - The mutagenic potential of antiestrogens at the HPRT locus in V79 cells.
AB  - Tamoxifen, a nonsteroidal antiestrogen is widely used in the treatment of breast
      cancer. Although clearly of clinical value, it produces adverse side effects
      associated with its estrogen agonist activity. This has led to the development of
      antiestrogens with less estrogen agonist activity. Analog II (1,1-dichloro-cis
      2,3-diaryl cyclopropane) is a cyclopropyl compound which produces pure
      antiestrogenic activity in mice and inhibits the proliferation of breast cancer
      cells. Since the genotoxicity of Analog II has not been examined, the aim of the
      present study was to investigate the mutagenic potential of Analog II. The
      mutagenic effects of Analog II were studied at the hypoxanthine phosphoribosyl
      transferase (hprt) locus in Chinese hamster lung fibroblasts (V79 cell line) and
      compared to tamoxifen and estradiol. In this study Analog II was not mutagenic at
      the hprt locus in V79 cells and appeared to have less mutagenic potential than
      either estradiol or tamoxifen. However, an examination of the genotoxicity of
      metabolic products of these compounds will be necessary before definite
      conclusions can be drawn concerning their genotoxicity in vivo.

PMID- 7582866
TI  - Relationship between alpha-tocopherol and polymorphonuclear leukocyte elastase in
      septic adult respiratory distress syndrome.
AB  - To elucidate the interrelationship between active oxygen and polymorphonuclear
      leukocyte elastase (PMN elastase) in patients with septic adult respiratory
      distress syndrome (ARDS), we examined the relationship between alpha-tocopherol,
      which has an antioxidant action, and PMN elastase. Serial blood samples were
      collected from 16 patients with septic ARDS. Serum levels of alpha-tocopherol
      were determined by HPLC. PMN elastase was determined by ELISA. The serum alpha
      tocopherol level in a nonsurviving group was significantly lower than that in a
      surviving group at the time that septic ARDS was diagnosed (p = 0.0068). The
      level of PMN elastase in the nonsurviving group was significantly higher than
      that in the surviving group (p = 0.0058). A significant negative correlation
      existed between the serum levels of alpha-tocopherol and those of PMN-elastase (r
      = -0.659, p = 0.0043). Both the serum alpha-tocopherol level and the PMN elastase
      level appeared to be good indices of the severity of ARDS. The results suggested
      that an interaction between active oxygen and PMN elastase may increase the
      clinical severity of this disease.

PMID- 7582867
TI  - Deficient ferritin immunoreactivity in visceral organs from four patients with
      Niemann-Pick disease type C.
AB  - Ferritin, the major iron storage protein, was found to be undetectable on
      immunoblot analysis of spleen and liver extracts from four patients with Niemann
      Pick disease type C (NPC). The patients had died from different clinical forms of
      this storage disease of still unknown etiology. The absence of ferritin
      immunoreactivity was shown using two different antisera, raised in rabbits,
      against ferritin from human spleen containing predominantly light-chain subunits
      (L-ferritin). Further evidence of absent L-ferritin in visceral tissues was
      provided by immunohistochemical studies performed in one of the four NPC
      patients. However, heavy-chain and light-chain ferritin mRNAs could be identified
      in cultured fibroblasts from this patient. The finding of deficient ferritin
      immunoreactivity is suggestive of an additional biochemical abnormality that is
      as marked as the known impairment of the transport of exogenously derived
      cholesterol in this complex lysosomal storage disorder.

PMID- 7582868
TI  - Flow cytofluorometric detection of inflammatory processes by measuring
      respiratory burst reaction of peripheral blood neutrophils.
AB  - This report describes a method for measuring the respiratory burst in
      neutrophils, based on intracellular oxidation of the reduced ethidium bromide
      derivative, hydroethidine. Fluorescence of the resultant product quantitatively
      determined by flow cytofluorometry serves as a measure of the neutrophil ability
      to generate superoxide radicals. We found that during inflammation some
      polymorphonuclear leukocytes showed a considerably lower respiratory burst
      response to phorbol myristate acetate treatment. It was demonstrated that
      variations in this parameter could be an indicator of the course of inflammation.

PMID- 7582864
TI  - Differential significance of nitric oxide in hypotensive mechanisms of
      acetylcholine and histamine in dogs.
AB  - The nitric oxide synthase inhibitor, NG-nitro-L-arginine, suppressed hypotensive
      response to acetylcholine, but not to histamine, in pentobarbital-anesthetized
      dogs. Infusions of acetylcholine increased plasma cyclic GMP levels, while
      histamine infusions did not. These results indicate that there is an apparent
      difference in the contributions of nitric oxide to the hypotensive mechanisms of
      acetylcholine and histamine.

PMID- 7582869
TI  - Antigenic and functional conservation of an integrin I-domain in Saccharomyces
      cerevisiae.
AB  - We sought evidence for precursors of the leukocyte integrin subunits alpha M and
      alpha X among unicellular eukaryotes such as Saccharomyces cerevisiae.
      Chromatography of cytosolic extracts of Saccharomyces cerevisiae on an affinity
      matrix coupled to BU-15, a monoclonal antibody that recognizes alpha X, revealed
      a band of M(r) > 205 kDa under nonreducing conditions. Screening a lambda gt11
      library of S. cerevisiae DNA with BU-15 (anti-alpha X) and anti-Mo1 (anti-alpha
      M) led to the isolation of a 3.7-kb EcoRI fragment containing the 3' end of an
      open reading frame sufficient to encode a polypeptide in excess of 118 kDa. On
      the basis of Southern blotting at high stringency, this gene was present in S.
      cerevisiae, but not in other yeast species such as Candida glabrata. Analysis of
      the derived amino acid sequence demonstrated > 98% identity with the S.
      cerevisiae protein Uso1p, a myosin-like polypeptide found exclusively in the
      cytosol. The C-terminal 1016 aa, expressed from the 3.7-kb EcoRI fragment in
      Escherichia coli as a beta-galactosidase fusion protein, bound iC3b, a ligand for
      the I-domain in alpha M and alpha X, and were recognized by Mn41, a monoclonal
      antibody specific for the alpha M I-domain. Antigenic and functional conservation
      of an I-domain in S. cerevisiae suggests that this domain may be a prototype for
      integrin-like proteins in other primitive eukaryotes.

PMID- 7582870
TI  - Hydrolysis of succinic acid dimethyl ester in rat pancreatic islets.
AB  - The hydrolysis of the dimethyl ester of [1,4-14C]succinic acid and/or [2,3
      14C]succinic acid was measured in homogenates of rat pancreatic islets, liver,
      jejunum, brain, BC3H1 mouse myocytes, NG108-19 mouse neuroblastoma x rat glioma
      hybrid cells, and Caco-2 human colon adenocarcinoma cells. The specific activity
      of the enzyme was much higher in liver, jejunum, and Caco-2 cells than in the
      other cell types. The affinity of the enzyme for succinic acid dimethyl ester
      (SAD) was also much higher in liver than in islet homogenates. In the latter
      case, both particulate and cytosolic activity were observed upon subcellular
      fractionation. The activity found in islet homogenates was commensurate with the
      rate of SAD hydrolysis in intact cells. While the intracellular pool of acidic
      metabolites generated from SAD remained fairly stable over a 15- to 120-min
      incubation and was mainly located in the cytosolic compartment, the amount of
      acidic metabolites released in the extracellular milieu progressively increased
      with the length of incubation. Such metabolites included both monocarboxylic and
      dicarboxylic acids, the latter consisting mainly of succinic acid and, to a much
      lesser extent, of fumaric acid and malic acid. However, at variance with SAD,
      succinic acid failed to be taken up by intact islets. There was no close
      parallelism between the specific activity of the SAD esterase and the extent of
      SAD utilization in distinct cell types.

PMID- 7582872
TI  - Metabolism of guanine and guanine nucleotides in primary rat cardiomyocyte
      cultures.
AB  - The metabolic fate of labeled guanine and of prelabeled guanine nucleotides
      (GuRN) was studied in cultured rat cardiomyocytes. Special attention was given to
      guanine salvage in comparison to degradation; to the contribution of GuRN to
      adenine nucleotides (AdRN); to the fluxes from GMP to IMP and from IMP to GMP;
      and to the degradation pathways of GuRN. In accordance with the 3- to 4-fold
      higher activity of guanine deaminase (guanase), in comparison to that of
      hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the rate of guanine
      deamination to xanthine exceeded that of guanine incorporation into nucleotides
      (at 4 microM) by 13.2-fold. The label from guanine incorporated into nucleotides
      was found mainly (81%) in GuRN, but also in IMP and AdRN. The prelabeled GuRN
      lost 43% of the label in 4 h, reflecting mainly degradation to xanthine (and uric
      acid) and synthesis of nucleic acids. Blocking nucleoside degradation was
      associated with a marked accumulation of label in guanosine and inosine
      (guanosine/inosine labeling ratio is 1.25). The results indicate that in the
      myocardium guanine is a poor substrate for salvage synthesis of GuRN and that its
      contribution to the homeostasis of adenine nucleotides is negligible; that GMP
      degradation to xanthine proceeds through both guanosine and IMP; and that the
      cardiomyocytes contain the activity of GMP reductase and of the enzymes
      converting IMP to GMP.

PMID- 7582871
TI  - Substrate accessibility to cytosolic aspartate aminotransferase improves
      posthypoxic recovery of isolated rat heart.
AB  - The effects of aspartate (Asp) and 2-oxoglutarate (2-OG) on metabolism and
      function of isolated rat heart during hypoxia and reoxygenation were studied.
      Hearts were subjected to oxygenated perfusion with Krebs-Henseleit buffer
      supplied with 11 mM glucose (20 min) and anoxic perfusion with the buffer
      saturated with N2 (20 min), followed by reoxygenation (30 min). The substrate
      concentrations in the perfusate were 3.5 mM each. The additives had no effect on
      the energy metabolism and function of the oxygenated heart despite a two-fold
      rise in myocardial Asp and 2-OG. Substrate supplementation during anoxic
      perfusion resulted in reduced lactate dehydrogenase release and less depression
      of cardiac function. Prevention of Asp, glutamate, and 2-OG degradation in
      hypoxic myocardium was accompanied by relief of glycolytic flux and better
      preservation of ATP, phosphocreatine (PCr), and total creatine (Cr).
      Reoxygenation without the additives after supplemented anoxic perfusion failed to
      improve recovery of high-energy phosphates and cardiac function compared to
      control. However, during reoxygenation with the additives the treated hearts
      showed less cell membrane damage and enhanced recovery of contractile and pump
      function. These effects were associated with higher myocardial contents of ATP,
      PCr, and adenine nucleotides and a smaller Cr loss during reoxygenation. A more
      effective restoration of oxidative metabolism was related to promoted glucose
      oxidation due to replenishment of the malate-aspartate shuttle reactants. The
      results substantiate the use of substrates of cytosolic aspartate
      aminotransferase for myocardial protection against hypoxia/reoxygenation stress.

PMID- 7582873
TI  - Effect of apolipoprotein E polymorphism on fasting retinyl palmitate level.
AB  - The effect of apolipoprotein E (apo E) common genotypes on fasting retinyl
      palmitate (RP) level was studied in 344 white individuals, of which 130 had
      intimal thickening of the carotid artery ("cases") and 214 were controls. In this
      sample the common apo E genotypes possessed a statistically significant effect on
      fasting RP level in cases, while in controls the effect observed was not
      statistically significant. It is suggested that the effect of apo E may be
      expressed at the level of remnant clearance particles. Additionally, in cases
      other traits interact with the apo E genotype to influence fasting RP level.

PMID- 7582874
TI  - Compartmentation and metabolic parameters of mitochondrial hexokinase and
      creatine kinase depend on the rate of oxidative phosphorylation.
AB  - Oxidative phosphorylation in rat heart mitochondria was stimulated by the
      presence of hexokinase, by simultaneous operation of mitochondrial hexokinase and
      creatine kinase, or by mitochondrial hexokinase plus exogenously added
      phosphofructokinase. Under these conditions, 32Pi studies were conducted to
      estimate the extent of ATP compartmentation in the mitochondria in the vicinity
      of the active sites of hexokinase and creatine kinase. In all cases studied the
      extent of ATP compartmentation at 500 microM ATP concentration was no more than
      12%. Within the same experimental design, the extent of ATP compartmentation
      increased with an increase in the rate of oxidative phosphorylation. The degree
      of ATP compartmentation depended on the relative location of the enzyme and inner
      mitochondrial membrane: it was maximal in the vicinity of the creatine kinase
      active sites and minimal for that of phosphofructokinase. The difference in the
      extent of ATP compartmentation in the neighborhood of the active sites of
      hexokinase and creatine kinase diminished with an increase in the rate of
      oxidative phosphorylation. We conclude that there is an ATP concentration
      gradient in the mitochondrial intermembrane space during oxidative
      phosphorylation, the minimum concentration being at the surface of the inner
      membrane. It was found that stimulation of oxidative phosphorylation led to a
      decrease in the apparent constants, Km (MgATP) and Vmax, for the two enzymes,
      however, to different degrees. Possible reasons for the change in kinetic
      parameters of the above enzymes are discussed.

PMID- 7582875
TI  - Production of interleukin-6 by osteoblastic cells is independent of medium
      inorganic phosphate.
AB  - A state of severe bone loss is often observed in patients and animals suffering
      from phosphate (Pi) depletion. Conversely, Pi surfeit may have an anabolic effect
      on bone and may antagonize bone resorption. To study whether Pi has a direct
      effect on the production of the bone-resorbing interleukin-6 (IL-6) by
      osteoblasts, we cultured MC3T3-E1, UMR-106, and isolated rat calvaria cells in
      media containing varying concentrations of Pi (0-3 mM) and measured the
      production of IL-6 released into the media. IL-6 production was steady with time
      and was stimulated by parathyroid hormone, 1,25-dihydroxyvitamin D3, and
      interleukin-1 alpha. However, IL-6 production did not change with varying Pi
      concentrations. We concluded that the IL-6 production by osteoblastic cells is
      independent of the medium Pi.

PMID- 7582876
TI  - Effect of diabetes and dietary ubiquinone supplementation on the post
      translational modification of rat lens beta L crystallin.
AB  - The effect of streptozocin diabetes of 14 days duration on the integrity of
      lenticular crystallins has been determined by the measurement of characteristic
      markers of protein modification in the lens crystallins of rats. Further, the
      susceptibility of the crystallins to modification has also been determined by
      measurement of the same markers after the application of a metal-catalyzed
      oxidative insult in vitro. The results show that the previously reported
      increased post-translational modification of lens crystallins in vivo and
      increased susceptibility to modification in vitro of diabetic crystallins after
      21 days of uncontrolled diabetes are also evident after just 14 days of diabetes.
      Treatment of the diabetic animals with the antioxidant ubiquinone by dietary
      supplementation was unable to prevent the post-translational modifications
      sustained by the crystallin when subjected to diabetes in vivo or the increase in
      susceptibility to an in vitro oxidative stress. While the present results support
      the proposal that cataract formation is initiated by protein post-translational
      modification factors such as glycation, ubiquinone supplementation does not
      appear to be beneficial in the inhibition of post-translational crystallin
      modification in diabetic cataractogenesis.

PMID- 7582877
TI  - Schizophrenia and GABAA receptor subunit genes.
AB  - Alterations in gamma-aminobutyric acid (GABA) neurotransmission have been
      indirectly implicated in the pathogenesis of schizophrenia. Using nine multiplex
      pedigrees, we tested for linkage between schizophrenia and simple sequence repeat
      polymorphisms for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6,
      beta 1 and beta 3 subunit genes. Evidence of linkage was not found when assuming
      either autosomal dominant or autosomal recessive inheritance. The non-parametric
      sib pair test also did not reveal significant evidence of deviation from expected
      segregation ratios.

PMID- 7582880
TI  - Statistical pitfalls in detecting age-of-onset anticipation: the role of
      correlation in studying anticipation and detecting ascertainment bias.
AB  - Attempts to detect anticipation in datasets have been hampered by two statistical
      problems: confusion about the role of correlation, and ascertainment bias. We
      show three things. (1) Correlation and anticipation are two distinct phenomena,
      such that neither high nor low correlation necessarily reveals anything about
      anticipation. (2) Nor does correlation analysis (or its cousin, regression
      analysis) offer a way to detect ascertainment bias, as has been suggested.
      Demonstration of "regression to the mean" does not necessarily indicate the
      presence of ascertainment bias, either. (3) Finally, under certain special
      circumstances, one can test for anticipation without regard for ascertainment
      bias. However, these circumstances are limited and may prove of little practical
      value.

PMID- 7582879
TI  - Psychiatric disorders in relatives of probands with obsessive-compulsive disorder
      and co-morbid major depression or generalized anxiety.
AB  - The authors report findings from a blind, controlled study of obsessive
      compulsive disorder (OCD). Prevalence rates of generalized anxiety disorder (GAD)
      and major depressive disorder (MDD) were compared among first-degree relatives of
      probands with OCD and co-morbid GAD or MDD, respectively. Rates of MDD were not
      increased in relatives of probands with OCD and MDD; neither were rates of GAD
      increased in relatives of probands with OCD and GAD, although rates of GAD were
      increased among relatives of probands with OCD compared to relatives of healthy
      controls. The authors explore the implications of the findings.

PMID- 7582881
TI  - 1995 Park City Molecular Psychiatry Conference, 5-8 February 1995, Park City,
      Utah.
AB  - In sum, the Park City Conference provided a conducive environment for data
      presentation and interaction among investigators. Over the past year much
      progress has been made, including advances in the ascertainment of families,
      genotyping and analytic methods. A critical mass in the field appears realized
      and major advances may be forthcoming.

PMID- 7582884
TI  - Emesis in infants as a consequence of feedings.
AB  - Emesis is a common symptom resulting from adverse food reactions in infants. In
      this article the terms food allergy and food intolerance are defined and
      differentiated. The immunopathophysiology of food allergies is discussed along
      with useful diagnostic tests. Adverse reactions to common infant nutrients such
      as cow's milk and soy milk are described, and therapeutic use of "hypoallergenic"
      formulas is outlined.

PMID- 7582885
TI  - Disorders of the central and autonomic nervous systems as a cause for emesis in
      infants.
AB  - Vomiting in infants can be caused by a wide variety of neurological disorders.
      All involve stimulation of a central pattern generator for vomiting located in
      the brainstem, the nucleus tractus solitarius. This, in turn, projects to
      multiple motor nuclei involved in the vomiting reflex. The chemoreceptor trigger
      zone (the area postrema) in the floor of the fourth ventricle is a major afferent
      to the nucleus tractus solitarius that can be stimulated by pressure from
      hydrocephalus, closed head injuries, or tumors. Other neurological causes of
      vomiting discussed include migraine, epilepsy, and dysautonomia. The treatment of
      vomiting associated with nervous system disease may be very difficult unless the
      condition is acute and readily reversible.

PMID- 7582883
TI  - Metabolic and infectious disorders associated with emesis in infants.
AB  - Vomiting is associated with an endless array of medical and surgical conditions,
      including infectious and metabolic disorders. This article is designed to review
      the pathophysiological mechanism of vomiting in infants. There is tremendous
      overlap in the signs and symptoms associated with vomiting in infancy, and these
      will be described. Pertinent historical prospectives are examined including
      prenatal history, neonatal history, underlying conditions, recent or chronic
      medication usage, exposures to illnesses or toxin, and family history. Specific
      findings obtained during physical examination may help direct further assessment
      of the vomiting infant. Laboratory tests are essential to the evaluation of the
      infant with emesis. These studies serve not only to help assess the severity of
      illness in the vomiting infant, but also to aid in the appropriate collection and
      handling of specimens during the time of critical presentation that may be useful
      during what are often complex and confusing clinical courses. Therapeutic
      interventions including both specific and supportive modalities for infants with
      vomiting caused by infectious and metabolic disorders are discussed.

PMID- 7582882
TI  - Status report on molecular genetic studies of affective disorders.

PMID- 7582878
TI  - Search for a schizophrenia susceptibility gene on chromosome 18.
AB  - Nine multiplex schizophrenia families were genotyped with 15 microsatellite
      markers mapping to the short and long arm of chromosome 18. Assuming either
      autosomal dominant or recessive inheritance evidence of linkage was not found. In
      addition, the non-parametric sib pair test did not reveal significant evidence of
      linkage.

PMID- 7582887
TI  - Esophageal disorders associated with emesis in infants and children.
AB  - Regurgitation of esophageal contents is referred to as esophageal emesis or
      esophageal vomiting. It is most likely to be confused with symptoms arising from
      disease proximal or distal to the esophagus, particularly the latter. Therefore,
      it is important to distinguish between esophageal vomiting and typical vomiting,
      although in the former group, the regurgitated contents are ingested food and/or
      saliva; recognition of the exact site of the pathological disorder may
      necessitate investigation. A wide variety of investigations may be necessary.
      Disease processes to be considered in the diagnosis include congenital stricture,
      achalasia and other motility disorders of the esophagus, foreign-body impaction,
      and acquired strictures of the esophagus, such as peptic or corrosive strictures.

PMID- 7582888
TI  - Gastroesophageal reflux disease as a cause for emesis in infants.
AB  - Vomiting is a very common symptom associated with gastroesophageal reflux disease
      (GERD) in infancy, although no longer the most common symptom seen in infants
      with GERD. A thorough evaluation of these patients with clinical history,
      physical examination, and sophisticated diagnostic procedures is necessary to
      identify that the vomiting is from GERD. Extended esophageal pH monitoring is the
      most reliable diagnostic procedure used to confirm the presence or absence of
      GERD, and provides additional information regarding prognosis and the
      relationship of the GERD to respiratory complaints. The latter information allows
      the clinician to determine the optimal type of antireflux therapy offered to the
      vomiting infant with GERD. Reevaluation of the vomiting infant with suspected
      recurrent GERD after antireflux operation should not differ from the evaluation
      performed in an untreated infant with vomiting from suspected GERD.

PMID- 7582886
TI  - Pharyngeal and swallowing disorders in infants.
AB  - Although true vomiting is an unusual manifestation of pharyngeal or swallowing
      disorders in infants and children, the forceful regurgitation of feedings seen
      with respiratory distress in these children may be interpreted by the clinician
      as vomiting episodes. This scenerio usually is caused by structural abnormalities
      of the upper airway or swallowing discoordination placing food as an obstruction
      in the airway during feedings. A good clinical history and physical examination
      of affected children often will disclose an anatomic cause for regurgitated
      feedings, but swallowing disorders are more subtle and usually require a complete
      swallowing evaluation. The essential components in treating these problems in
      children include the removal of the airway obstruction or rehabilitation of
      feeding and swallowing. The approach to treatment is often multidisciplinary in
      nature and highly individualized.

PMID- 7582890
TI  - Hammerhead ribozyme structure: U-turn for RNA structural biology.
AB  - Two crystal structures of the hammerhead ribozyme provide the first atomic
      resolution views of an RNA active site, and suggest that the catalytic center may
      reside in a U-turn motif which was first seen in tRNA(Phe).

PMID- 7582891
TI  - 14-3-3 proteins: structure resolved, functions less clear.
AB  - The crystal structures of 14-3-3 proteins reveal that they form dimers with a
      deep groove running along the length of the dimer. The location of conserved
      residues in this groove suggests that it plays an essential role in the adaptor
      functions of these proteins.

PMID- 7582889
TI  - Gastroduodenal disorders associated with emesis in infants.
AB  - Emesis is a common occurrence in newborns and infants. The causes are ubiquitous
      and unfortunately nonspecific. However, clues exist with respect to the timing of
      the onset of emesis as well as to its character. Emesis can be bilious or
      nonbilious, projectile or nonprojectile, and in some patients it is effortless.
      Newborns and infants with emesis of gastric origin may display a paucity of
      visible external signs. Ultrasound, contrast radiographic studies, and endoscopy
      coupled with physical examination are invaluable in the assessment of the emesis.
      Important in the management is prompt correction of fluid and electrolyte losses.
      Surgical correction, if warranted, can then be undertaken with significant
      lessening of morbidity.

PMID- 7582892
TI  - Unraveling transposition: gamma delta resolvase in complex with DNA.
AB  - The structure of gamma delta resolvase with 34 base pair oligonucleotide reveals
      an intricate and novel complex of the protein with DNA and lays the foundations
      for understanding transposition at the atomic level.

PMID- 7582893
TI  - The science of macromolecular crystallization.

PMID- 7582895
TI  - Structural evidence for the evolutionary divergence of mycoplasma from gram
      positive bacteria: the histidine-containing phosphocarrier protein.
AB  - BACKGROUND: The three-dimensional structures of histidine-containing
      phosphocarrier protein (HPr), a member of the phosphoenolpyruvate:sugar
      phosphotransferase system (PTS), have been determined from Gram-negative and Gram
      positive bacteria. The structure of HPr reported here for Mycoplasma capricolum
      is the first protein structure to be determined for this class of organism.
      Comparative structural studies with the bacterial proteins highlight sequence
      structure correlations relevant to proposals about the evolutionary origin of
      mycoplasmas. RESULTS: The crystal structure of HPr from M. capricolum has been
      determined and refined at 1.8 A resolution, revealing the same overall fold as
      that of other HPrs of known structure. However, mycoplasma HPr resembles HPrs
      from Gram-positive bacteria more closely than those from Gram-negative bacteria.
      As in HPrs from Bacillus subtilis and Escherichia coli, the phosphoryl group
      carrier (His15) forms the N-terminal cap of a helix, but in contrast to the other
      crystal structures, the side chain of the adjacent Arg17 is conformationally
      disordered. A sulfate ion interacts with Ser46, a residue known to be
      phosphorylated in a regulatory manner. CONCLUSIONS: The greater degree of
      structural similarity of the M. capricolum HPr to HPrs from Gram-positive rather
      than Gram-negative bacteria is consistent with the proposal that mycoplasma
      evolved from Gram-positive bacteria. The proposal that no major conformational
      transition is required for phosphorylation of the active-site histidine is
      reinforced by comparing the crystal structures with and without an anion in the
      active site. The conformational disorder of the Arg17 side chain suggests that
      its guanidinium group does not have to form specific interactions with other
      protein groups before phosphorylation at His15. The association of a sulfate ion
      with Ser46 serves as a model for HPr(Ser46-P). As there is no evidence of a
      conformational change accompanying Ser46 phosphorylation, the inhibitory effect
      of this event may be attributable to altered surface electrostatics.

PMID- 7582896
TI  - Solution structure of the cardiostimulant polypeptide anthopleurin-B and
      comparison with anthopleurin-A.
AB  - BACKGROUND: The polypeptide anthopleurin-B (AP-B) is one of a number of related
      toxins produced by sea anemones. AP-B delays inactivation of the voltage-gated
      sodium channel of excitable tissue. In the mammalian heart, this effect is
      manifest as an increase in the force of contraction. As a result, there is
      interest in exploiting the anthopleurins as lead compounds in the design of novel
      cardiac stimulants. Essential to this endeavour is a high-resolution solution
      structure of the molecule describing the positions of functionally important side
      chains. RESULTS: AP-B exists in multiple conformations in solution as a result of
      cis-trans isomerization about the Gly40-Pro41 peptide bond. The solution
      structure of the major conformer of AP-B has been determined by two-dimensional
      1H NMR at pH 4.5 and 25 degrees C. The core structure is a four-stranded,
      antiparallel beta-sheet (residues 2-4, 20-23, 34-37 and 45-48) and includes
      several beta-turns (6-9, 25-28, 30-33). Three loops connect the beta-strands, the
      longest and least well defined being the first loop, extending from residues 8
      17. These features are shared by other members of this family of sea anemone
      toxins. The locations of a number of side chains which are important for the
      cardiac stimulatory activity of AP-B are well defined in the structures.
      CONCLUSIONS: We have described the solution structure of AP-B and compared it
      with that of AP-A, from which it differs by substitutions at seven amino acid
      positions. It shares an essentially identical fold with AP-A yet is about 10-fold
      more active. Comparison of the structures, particularly in the region of residues
      essential for activity, gives a clearer indication of the location and extent of
      the cardioactive pharmacophore in these polypeptides.

PMID- 7582897
TI  - Structure and function of a virally encoded fungal toxin from Ustilago maydis: a
      fungal and mammalian Ca2+ channel inhibitor.
AB  - BACKGROUND: The P4 strain of the corn smut fungus, Ustilago maydis, secretes a
      fungal toxin, KP4, encoded by a fungal virus (UMV4) that persistently infects its
      cells. UMV4, unlike most other (non-fungal) viruses, does not spread to
      uninfected cells by release into the extracellular milieu during its normal life
      cycle and is thus dependent upon host survival for replication. In symbiosis with
      the host fungus, UMV4 encodes KP4 to kill other competitive strains of U. maydis,
      thereby promoting both host and virus survival. KP4 belongs to a family of fungal
      toxins and determining its structure should lead to a better understanding of the
      function and evolutionary origins of these toxins. Elucidation of the mechanism
      of toxin action could lead to new anti-fungal agents against human pathogens.
      RESULTS: We have determined the atomic structure of KP4 to 1.9 A resolution. KP4
      belongs to the alpha/beta-sandwich family, and has a unique topology comprising a
      five-stranded antiparallel beta-sheet with two antiparallel alpha-helices lying
      at approximately 45 degrees to these strands. The structure has two left-handed
      beta alpha beta cross-overs and a basic protuberance extending from the beta
      sheet. In vivo experiments demonstrated abrogation of toxin killing by Ca2+ and,
      to a lesser extent, Mg2+. These results led to experiments demonstrating that the
      toxin specifically inhibits voltage-gated Ca2+ channels in mammalian cells.
      CONCLUSIONS: Similarities, although somewhat limited, between KP4 and scorpion
      toxins led us to investigate the possibility that the toxic effects of KP4 may be
      mediated by inhibition of cation channels. Our results suggest that certain
      properties of fungal Ca2+ channels are homologous to those in mammalian cells.
      KP4 may, therefore, be a new tool for studying mammalian Ca2+ channels and
      current mammalian Ca2+ channel inhibitors may be useful lead compounds for new
      anti-fungal agents.

PMID- 7582898
TI  - The 70S Escherichia coli ribosome at 23 A resolution: fitting the ribosomal RNA.
AB  - BACKGROUND: The ribosome--essential for protein synthesis in all organisms--has
      been an evasive target for structural studies. The best available structures for
      the 70S Escherichia coli ribosome or its 30S and 50S subunits are based on
      electron microscopical tilt experiments and are limited in resolution to 28-55 A.
      The angular reconstitution approach, which exploits the random orientations of
      particles within a vitreous ice matrix, can be used in conjunction with cryo
      electron microscopy to yield a higher-resolution structure. RESULTS: Our 23 A
      resolution map of the 70S ribosome elucidates many structural details, such as an
      extensive system of channels within the 50S subunit and an intersubunit gap
      ideally shaped to accommodate two transfer RNA molecules. The resolution achieved
      is sufficient to allow the preliminary fitting of double-helical regions of an
      earlier three-dimensional ribosomal RNA model. CONCLUSIONS: Although we are still
      a long way from attaining an atomic-resolution structure of the ribosome, cryo
      electron microscopy, in combination with angular reconstitution, is likely to
      yield three-dimensional maps with gradually increasing resolution. As exemplified
      by our current 23 A reconstruction, these maps will lead to progressive
      refinement of models of the ribosomal RNA.

PMID- 7582899
TI  - The solution structure and backbone dynamics of the fibronectin type I and
      epidermal growth factor-like pair of modules of tissue-type plasminogen
      activator.
AB  - BACKGROUND: The thrombolytic serine protease tissue-type plasminogen activator (t
      PA) is a classical modular protein consisting of three types of domain in
      addition to the serine protease domain: F1 (homologous to fibronectin type I); G
      (epidermal growth factor-like) and kringle. Biochemical data suggest that the F1
      and G modules play a major role in the binding of t-PA to fibrin and to receptors
      on hepatocytes. RESULTS: We have derived the solution structure of the F1 and G
      pair of modules from t-PA by two- and three-dimensional NMR techniques, in
      combination with dynamical simulated annealing calculations. We have also
      obtained information about the molecule's backbone dynamics through measurement
      of amide 15N relaxation parameters. CONCLUSIONS: Although the F1 and G modules
      each adopt their expected tertiary structure, the modules interact intimately to
      bury a hydrophobic core, and the inter-module linker makes up the third strand of
      the G module's major beta-sheet. The new structural results allow the
      interpretation of earlier mutational data relevant to fibrin-binding and
      hepatocyte-receptor binding.

PMID- 7582900
TI  - High-resolution macromolecular structure determination using CCD detectors and
      synchrotron radiation.
AB  - BACKGROUND: Synchrotron radiation sources have made impressive contributions to
      macromolecular crystallography. The delay in development of appropriate X-ray
      detectors has, however, been a significant limitation to their efficient use. New
      technologies, based on charge-coupled devices (CCDs), provide capabilities for
      faster, more accurate, automated data collection. RESULTS: A CCD-based X-ray
      detector has been developed for use in macromolecular crystallography and has
      been in operation for about one and a half years at the Cornell High Energy
      Synchrotron Source. It has been used for a variety of crystallographic projects,
      including a number of high-resolution structural studies. The statistical quality
      of the data, the detector's ease and efficiency of use, and the growing number of
      structural results illustrate the practical utility of this new detector system.
      CONCLUSIONS: The new detector has enhanced capabilities for measuring diffraction
      patterns from crystals of macromolecules, especially at high resolution, when the
      X-ray intensities are weak. The survey of results described here ranges from
      virus crystallography to weakly diffracting small-molecule structure
      determination and demonstrates the potential of CCD detectors when combined with
      synchrotron radiation sources.

PMID- 7582901
TI  - Expression of CD11b and ICAM-1 in an in vivo model of transplant
      arteriosclerosis.
AB  - Adhesion molecules play a crucial role in transplant rejection in regulating the
      interaction of inflammatory cells with cells in the vascular wall. In an aortic
      transplantation model, we have previously analysed the early adhesion process
      (7.5 min to 24 h) and the impact of cold ischaemia time (1-24 h) upon transplant
      arteriosclerosis during the first 2 months after transplantation in the rat. The
      aim of this investigation was to study adhesion molecules in accelerated
      transplant arteriosclerosis in a rat model by analysing the immunohistochemical
      expression of CD11b and ICAM-1 up to 2 months and followed by a semiquantitative
      evaluation and multivariant analysis. Antigen expression of CD11b and ICAM-1
      adhesion molecules was stronger in the aortic allografts than in the ischaemia
      induced syngeneic aortic grafts in the whole vessel wall. Neither ICAM-1 nor
      CD11b antigen expression correlated significantly with time periods of
      ischaemia/reperfusion injury in allogeneic or syngeneic aortic transplants. CD11b
      and ICAM-1 are induced by allogeneic stimuli in transplanted aortas suggesting a
      role in the pathogenesis of transplant arteriosclerosis. Our findings have
      implications for understanding the role of cell adhesion activation in the
      vascular wall subject to chronic graft rejection.

PMID- 7582894
TI  - Crystal structure of the superantigen enterotoxin C2 from Staphylococcus aureus
      reveals a zinc-binding site.
AB  - BACKGROUND: Staphylococcus aureus enterotoxin C2 (SEC2) belongs to a family of
      proteins, termed 'superantigens', that form complexes with class II MHC molecules
      enabling them to activate a substantial number of T cells. Although superantigens
      seem to act by a common mechanism, they vary in many of their specific
      interactions and biological properties. Comparison of the structure of SEC2 with
      those of two other superantigens--staphylococcal enterotoxin B (SEB) and toxic
      shock syndrome toxin-1 (TSST-1)--may provide insight into their mode of action.
      RESULTS: The crystal structure of SEC2 has been determined at 2.0 A resolution.
      The overall topology of the molecule resembles that of SEB and TSST-1, and the
      regions corresponding to the MHC class II and T-cell receptor binding sites on
      SEB are quite similar in SEC2. A unique feature of SEC2 is the presence of a zinc
      ion located in a solvent-exposed region at the interface between the two domains
      of the molecule. The zinc ion is coordinated to Asp83, His118, His122 and Asp9*
      (from the neighbouring molecule in the crystal lattice). Atomic absorption
      spectrometry demonstrates that zinc is also bound to SEC2 in solution.
      CONCLUSIONS: SEC2 appears to be capable of binding to MHC class II molecules in
      much the same manner as SEB. However, structure-function studies have suggested
      an alternative binding mode that involves a different site on the toxin. The zinc
      ion of SEC2 lies within this region and thus may be important for complex
      formation, for example by acting as a bridge between the two molecules. Other
      possible roles for the metal cation, including a catalytic one, are also
      considered.

PMID- 7582902
TI  - Expression of stress proteins and lymphocyte reactivity in heterotopic cardiac
      allografts undergoing cellular rejection.
AB  - This report addresses the concept that, during rejection, the allograft undergoes
      a stress response which leads to an increased expression of stress proteins, also
      called heat shock proteins (hsp), and the recruitment and activation of hsp
      reactive lymphocytes. Recent studies in our laboratory have provided evidence
      that hsp-reactive T-cells are present in cardiac allografts undergoing rejection.
      In this study, an MHC incompatible heterotopic heart allograft model (ACI into
      LEW) was chosen to analyse the kinetics of hsp expression during the development
      of rejection. Allografts and syngrafts (LEW into LEW) were harvested every day
      during the first 5 days post-transplant. Immunoblot analysis of proteins
      extracted from graft stromal tissues was done with murine monoclonal antibodies
      (mAb) against various mammalian hsp. Proliferation studies were done to determine
      hsp reactivity of graft-infiltrating lymphocytes on different days post
      transplant. Three types of stressful stimuli appeared to increase hsp expression
      in the allograft. The first was a physiological stress secondary to the trauma of
      the transplant procedure and ischaemia/reperfusion injury and this would occur in
      allogeneic and syngeneic grafts. During the first day after transplantation, both
      types of grafts showed higher expression of hsp72 and grp78 and to a lesser
      extent, hsp60 and grp75. On the second and third day, the expression of grp78 and
      grp96 was higher in allografts than in syngrafts and this may reflect an
      immunologically mediated stress response in the allograft when infiltrating hsp
      reactive lymphocytes became first detectable in the allograft. The third type of
      stress appeared related to the inflammatory process associated with rejection. On
      the fourth and fifth day post-transplant, the allografts showed strong expression
      of at least five proteins of lower molecular mass reacting with hsp-specific
      mAbs; namely, approximately 40 kDa (detected by anti-hsp60), approximately 30 kDa
      (by anti-hsp72), approximately 45 kDa and approximately 32 kDa (by anti-hsp72 +
      hsc73), and approximately 50 kDa (by anti-grp78). At that time, the allograft
      began to show progressive inflammatory changes and tissue damage. The appearance
      of lower molecular mass hsp-crossreactive proteins might reflect a degradation of
      hsps which had increased expression earlier during the post-transplant period.
      This process may generate large quantities of hsp-derived peptides which may be
      presented by MHC molecules to graft-infiltrating T-cells. Another interpretation
      of the strong expression of lower molecular bands in later allografts is that
      they represent other stress proteins that crossreact with antibodies against
      hsp60 and hsp70 family members.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7582904
TI  - Immunosuppressive properties of cultured human cornea and ciliary body in normal
      and pathological conditions.
AB  - Corneal transplantations may survive when transplanted orthotopically even in the
      presence of massive corneal neovascularization, while such grafts would be
      rejected in heterotopic locations. Experiments with murine tissues have shown
      that cultured corneal tissue as well as iris/ciliary body (I/CB) tissue produce
      immunosuppressive factors. This was not the case when traumatized corneas were
      tested. We therefore wondered whether the same difference could be observed when
      explants of normal or pathological human corneas or I/CB tissues were tested.
      Supernatant of cultured cornea and I/CB tissue was added to a mixed lymphocyte
      reaction (BALB/c responder and C57B1/6 stimulator cells) and thymidine
      incorporation was measured. Culture supernatants from normal corneas and corneas
      with bullous keratopathy achieved similar levels of MLR inhibition, which could
      not be blocked by addition of anti-transforming-growth factor-beta 2 antibody or
      indomethacin. The supernatant from cultured I/CB cells from normal eyes and from
      eyes containing a posterior segment melanoma did not differ in their
      immunosuppressive effect. The MLR inhibitory effect of supernatant from I/CB
      cells was partly blocked by addition of indomethacin. We conclude that MLR
      inhibiting factors are produced by normal and pathological corneas and by I/CB
      cells, but the supernatants from these tissues achieve their effect by different
      means. It is likely that the ability of cornea and I/CB tissues to produce
      immunosuppressive factors contributes to the success of orthotopic corneal
      transplants in man.

PMID- 7582903
TI  - Donor specific bone marrow cells suppress lymphocyte reactivity to donor antigens
      and differentially modulate TH1 and TH2 cytokine gene expression in the responder
      cell population.
AB  - Previous studies have shown that post-transplantation infusion of donor specific
      bone marrow following a non-specific potent immunosuppressive agent such as
      antilymphocyte globulin (ALG) can significantly enhance graft survival compared
      to ALG alone. This enhancement remains variable and is thought to occur through
      the induction of specific partial tolerance to the renal allograft, but the
      underlying cellular mechanisms have not been clearly identified. In order to
      improve the efficacy of this specific immunosuppressive treatment and to study
      the events leading to enhanced allograft survival, we sought to establish a
      simple in vitro model based on a mixed lymphocyte reaction (MLR). We show that
      cellular proliferation seen in a normal MLR can be suppressed by addition of
      donor specific bone marrow cells (BMC). Significantly, this suppression is not
      observed with either third party BMC or donor specific peripheral blood
      mononuclear cells (PBMC). We have defined the optimum conditions of bone marrow
      infusion regarding number of BMC, their handling and culture, and simple
      enrichment procedures. Using a semiquantitative polymerase chain reaction assay,
      we have studied the cytokine gene expression in MLR modulated by donor specific
      BMC. In an unmodified allogeneic response, the responder cells show increased
      expression of interleukin-2 (IL-2) gamma-interferon IFN-gamma and receptor (IL
      2R) mRNA, and no IL-10 mRNA. When responder cells are cultured with BMC of the
      stimulator, there is a 256-fold decrease in IL-2 mRNA, and a 64-fold decrease in
      IFN-gamma and IL-2R mRNA. There is also a 64-fold increase in IL-10 mRNA. This
      effect is even more marked when the BMC are depleted of CD3+ cells. The kinetics
      of addition of donor specific BMC to the normal allogeneic MLR culture and
      specificity of the action of BMC are also elucidated. Our data suggest that the
      enhancement of graft survival observed with donor BMC may operate through
      decreased proliferation of reactive T cell clones (due to decreased IL-2/IL-2R)
      and suppressed monocyte functions (due to decreased IFN-gamma and increased IL-10
      gene expression).

PMID- 7582905
TI  - Viral peptide specific cytotoxic T lymphocytes are of high avidity to host-MHC
      but only low avidity to donor-MHC after allogeneic bone marrow transplantation.
AB  - In the thymus maturing T lymphocytes are positively selected for efficient
      interaction with self-MHC molecules. Consequently, mature peripheral T cells
      recognize foreign (microbial) antigens in association with self-MHC molecules
      (known as MHC restricted recognition). In experimental bone marrow
      transplantation (BMT) lymphohaemopoietic stem cells from an MHC disparate donor
      transfused to an irradiated host give rise to mature T lymphocytes with host-MHC
      restriction specificity. While experiments with T cell receptor transgenic mice
      have largely confirmed this concept, many studies using genetically unmanipulated
      animals analysing polyclonal T cell repertoires have also shown donor-MHC
      restricted T cell activities after allogeneic BMT. To analyse this discrepancy we
      generated 18 virus specific cytotoxic T cell (CTL) clones, 16 from F1 into parent
      and two from fully allogeneic bone marrow chimeras, and analysed the MHC
      restriction specificity in proliferation and cytotoxicity assays. The
      cytotoxicity of all the clones was primarily host-MHC restricted. However, the
      CTL clones proliferated to viral antigen presented by both donor- or host-MHC.
      Our model allowed CTL cloning by cross-specific stimulation with antigen plus
      either donor-MHC or else host-MHC. Interestingly, even the 14 CTL clones which
      had been raised with donor-MHC systematically killed host-MHC but not donor-MHC
      expressing cells. Thus, after BMT, CTLs may proliferate crossreactively to donor
      MHC but cytolysis is predominantly directed to host-MHC expressing cells. Since
      lytic CTL activity probably reflects high avidity CTL interaction necessary for
      viral clearance in vivo, the data suggest that the donor-MHC restricted CTL
      activity may not be protective and that virus may escape CTL surveillance in
      donor cells.

PMID- 7582906
TI  - Cytokine gene expression in rejecting and tolerant rat lung allograft models:
      analysis by RT-PCR.
AB  - Cytokine gene expression is a critical component of the lung allograft rejection
      (AR) response and tolerance development in rat models. In order to determine the
      specificity of cytokine gene expression for AR and tolerance, we examined
      cytokine (interleukin-2) (IL-2), (gamma-interferon) (gamma-IFN), IL-4, IL-10 and
      tumor necrosis factor-alpha (TNF-alpha) and control (cyclophilin) mRNA levels in
      two models of rat lung allograft rejection by RT-PCR (reverse transcriptase
      polymerase chain reaction), Southern blotting. The first model (WKY-->F344)
      develops a mild to moderate lymphocytic infiltrate on days 14-21 post-transplant
      (stage II-III AR), which spontaneously resolves by day 35 post-transplant with
      subsequent development of allograft tolerance (grafts surviving without evidence
      of AR for > 140 days). Conversely, F344-->WKY develops a similar lymphocytic
      infiltrate by day 14 post-transplant, but by day 21 post-transplant the graft
      shows severe AR (stage III-IV) and has haemorrhagic infarction with alveolar
      haemorrhage. METHODS: RNA was extracted from allografts removed on days 3, 7, 14,
      21, 35 and 42 post-transplant. Five animals for each group (WKY-->F344) and F344-
      >WKY) were examined at each time point, except that no animals in the F344-->WKY
      were examined on day 42. cDNA was synthesized from total extracted RNA and
      primers specific for rat TNF-alpha, rat IL-2, rat gamma-IFN, rat IL-4, rat-IL-10
      and rat cyclophilin were used for gene-specific amplification. (TNF-alpha, gamma
      IFN, IL-10, 20 cycles; IL-2, IL-4, 30 cycles; cyclophilin, 20 cycles). The cycles
      numbers chosen for comparison were found to be optimal during preliminary
      experiments and occurred during the exponential phase of amplification. PCR
      products were electrophoresed on a polyacrylamide gel and silver-stained. Gels
      were subsequently electrotransferred to nylon membranes which were probed with
      murine cDNAs specific for IL-2, gamma-IFN IL-4, IL-10 and TNF-gamma. RESULTS:
      Cyclophilin gene expression was similar for both models at all time points
      tested; this also served as an internal standard for RT-PCR. In the WKY-->F344
      tolerance model, TNF-alpha mRNA levels were not detectable on days 3 and 7 post
      transplant, were at very low levels on day 14 and were undetectable on day 21
      post-transplant. In marked contrast, the F344-->WKY rejection model showed TNF
      alpha mRNA present on day 3 which increased markedly on day 7 and peaked on day
      14 post-transplant. TNF-alpha mRNA levels decreased on days 21 and 35 post
      transplant, a time when the lung was undergoing AR. The pattern of IL-2 and gamma
      IFN mRNA expression was similar to that for TNF-alpha. However, IL-2 mRNA was
      clearly detectable in the WKY-->F344 tolerance model on day 7 and gamma-IFN was
      not present until day 14 post-transplant. The F344-->WKY rejection model showed
      very high levels of IL-2 and gamma-IFN on day 3 which peaked on day 14. The ratio
      of IL-2/IL-10 in the F344-->WKY rejection model was more than 5 times that seen
      in the WKY-->F344 tolerance model on day 3 (p < 0.0005). The ratio of IL-2/IL-4
      was higher (1.5 times) in the F344-->WKY rejection model than in the WKY-->F344
      tolerance model (p < 0.007) on day 3. On day 14 post-transplant, the IL-2/IL-10
      ratio in the F344-->WKY rejection model was three times that of the tolerance
      model (p < 0.0015). The IL-2/IL-4 ratio was 3.5 times greater in the WKY-->F344
      tolerance model than in the rejectin model (p < 0.003). This was due to equal
      expression of IL-2 and IL-4 in the rejection model, but poor IL-4 expression in
      the tolerance model. CONCLUSIONS: 1) The WKY-->F344 tolerance model develops mild
      to moderate lymphocytic infiltrates on day 14 which is associated with low level
      IL-2, gamma-IFN and TNF-alpha gene expression. IL-10 and IL-4 are present at day
      3; however, by day 14, IL-10 is the predominantly expressed Th2 cytokine and IL-4
      is not expressed. The infiltrates ultimately resolve and the animals develop a
      functional tolerance to their grafts.4

PMID- 7582907
TI  - Expression of the cytotoxic T cell mediator granzyme B during liver allograft
      rejection.
AB  - Cytotoxic T lymphocytes (CTL) constitute a major component of the alloreactive
      response following organ transplantation. The molecular mechanisms of CTL killing
      remain to be determined but multiple candidate molecules involved in CTL-mediated
      cytotoxicity have been identified. Granzyme B, a serine protease, participates in
      perforin-dependent pathways of cytotoxicity and is necessary for induction of DNA
      fragmentation in target cells. In this study the expression of granzyme B in
      liver biopsies obtained from liver allograft recipients was determined by
      semiquantitative reverse transcriptase polymerase chain reaction. Biopsies were
      classified into four groups--no evidence of rejection, preservation injury, acute
      rejection, or resolving rejection--according to histopathological criteria. There
      was a significantly higher frequency of transcripts for granzyme B in the acute
      rejection group (82.8%) compared to the no rejection (20.0%), resolving rejection
      (12.5%) and preservation injury (0%) groups. Analysis of granzyme B gene
      expression in sequential samples from individual patients prior to, and after,
      treatment for rejection revealed an inverse correlation between granzyme B mRNA
      and response to treatment. These findings indicate that the cytopathic mediator
      granzyme B may participate in CTL-mediated cytotoxicity during liver allograft
      rejection.

PMID- 7582908
TI  - A new cyclosporin derivative, SDZ-IMM-125, prolongs renal allograft survival in
      dogs.
AB  - Previous studies in vitro and in rodent transplantation models have suggested
      that an analogue of cyclosporin, SDZ-IMM-125, has immunosuppressive properties at
      least equivalent to that of cyclosporin. As the bioavailability of the drug was
      considered to be greater than that of cyclosporin, it was hoped that lower doses
      could be used with the avoidance of nephrotoxicity. Renal allografts were
      undertaken between beagle dogs from two partially inbred breeding colonies. After
      transplantation, SDZ-IMM-125 was given orally at a dosage of 5, 7.5, 10 or 20
      mg/kg/day, and graft survival compared to that in dogs given cyclosporin 10 mg/kg
      or in untreated animals. The results showed that SDZ-IMM-125 is immunosuppressive
      in dogs and prolongs graft survival up to 50 days at a dosage of 20 mg/kg/day.
      However, at this dose histological changes suggestive of liver toxicity were
      observed in one dog, and mild anaemia was produced,but there was no evidence of
      nephrotoxicity. Absorption profiles suggested that the drug is rapidly absorbed
      and metabolized, and that a more frequent daily dosage may be appropriate.
      Overall, there appeared to be no significant advantage for the analogue SDZ-IMM
      125 over cyclosporin. The transplant model was associated with a high spontaneous
      renovascular thrombosis rate, particularly after cyclosporin administration,
      which was prevented by the daily administration of aspirin.

PMID- 7582909
TI  - Isolation of a 40 kDa immunoinhibitory protein induced by rat liver
      transplantation.
AB  - In certain combinations of donor and recipient rat strains, such as DA (RT1a)
      donors into PVG (RT1c) recipients, rejection after orthotopic liver
      transplantation (OLT) is overcome without immunosuppressive drugs, although other
      organs transplanted between these combinations are promptly rejected. The
      mechanisms involved in achieving drug-free liver allograft tolerance still remain
      poorly understood. In the present study, OLT (DA into PVG) serum from various
      postoperative times was analysed by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis and two unique proteins of 40 kDa and 37 kDa were found to be in
      large concentrations in 60 day post-OLT serum. These proteins could only be
      detected at specific times after OLT in the DA into PVG combination and could not
      be detected in the serum of syngenically transplanted animals (DA into DA) and
      (PVG into PVG), rejector combinations (DA into LEW) requiring immunosuppressive
      treatment or induced by other organ transplants. When these proteins were
      purified and sequenced they were found to have an identical N-terminal sequence
      which is not listed in sequence databases. Mixed lymphocyte assays revealed that
      only the 40 kDa protein has a immunosuppressive capability which additionally
      appears to be donor specific. The 40 kDa protein will aid further in the
      understanding of how drug-free tolerance is attained in certain liver allografts
      and may also act as a marker of when treatment with conventional
      immunosuppressive drugs can be stopped in clinical OLT providing a homologue of
      the molecule can be found. This possibility appears likely as case reports
      already exist of patients who have successfully been able to cease treatment with
      such drugs.

PMID- 7582910
TI  - Binding of lymphocytes to acutely rejecting rat kidney allografts in vitro is
      guided by events in the graft itself rather than by sensitization of host
      lymphocytes.
AB  - Circulating host lymphocytes recognize, bind to, become activated by, and
      infiltrate engrafted allogeneic tissues. The mechanisms responsible for these
      early events which lead to acute immunological rejection have not been precisely
      defined. We have examined sequentially in vitro lymphocyte binding patterns in a
      kidney transplant model of acute rejection in rats and their relationship to the
      expression of two representative adhesion molecules, ICAM-1 and LFA-1. The extent
      of binding of naive, or allosensitized recipient strain LNL or PBL, or donor
      strain or third party cells to frozen sections of kidney allografts was not
      significantly different; adherence was dependent upon whether the graft was an
      allograft or an isograft. The pattern of lymphocyte adherence to various
      allograft compartments was distinct and varied with time. Within 3 days after
      transplantation only a few cells had bound to the frozen tissues, preferentially
      to vascular endothelium. By days 5 and 7, increasing numbers of cells bound
      primarily to tubules, as did the few cells adhering to isografts.
      Immunohistologically, ICAM-1 expression increased progressively during acute
      rejection, first on vascular endothelium, later on tubules. LFA-1+ infiltrating
      cells peaked more quickly. Lymphocyte binding could be inhibited (approx. 40%) by
      monoclonal antibodies directed against LFA-1 and ICAM-1. The results indicate
      that in vitro lymphocyte binding to acutely rejecting kidney transplants is
      directed by the allogenicity of the graft itself via upregulation of adhesion
      molecules rather than sensitization of the host cells.

PMID- 7582911
TI  - A minimal conditioning approach to achieve stable multilineage mouse plus rat
      chimerism.
AB  - Transplantation of untreated rat bone marrow into lethally irradiated (950 cGy)
      mouse recipients results in durable xenogeneic (rat-->mouse) chimerism and
      confers donor-specific transplantation tolerance for subsequent xenografts. The
      purpose of the present study was to characterize the minimal dose of total body
      irradiation (TBI) which would allow engraftment of rat bone marrow in mouse
      recipients. We report here that durable and stable lymphohaematopoietic cross
      species chimerism can be achieved using a less than totally ablative radiation
      based conditioning approach. The percentage of B10 mouse recipients which
      engrafted with rat bone marrow cells correlated with the dose of TBI. Engraftment
      of rat bone marrow stem cells occurred in all animals receiving 750 cGy prior to
      bone marrow transplantation, while no engraftment was detected at doses less than
      650 cGy. Although most of the recipients were repopulated with mixed mouse and
      rat multilineage chimerism, some exhibited a predominance of rat cells. Although
      mixed xenogeneic rat/mouse chimeras prepared by lethal TBI produced only mouse
      derived RBC (red blood cells), chimeras prepared by sublethal conditioning
      produced both rat and mouse RBC. Only animals with detectable chimerism exhibited
      specific functional transplantation tolerance to donor xenoantigens, as assessed
      in vitro by mixed lymphocyte reaction assay. This model may offer an in vivo
      approach to study the role of species-specific growth factors in stem cell
      biology as well as the mechanisms for the induction of tolerance across species
      barriers.

PMID- 7582912
TI  - Human oocyte cytometry and fertilisation rate after subzonal insemination.
AB  - The cytometry of 545 oocytes was evaluated during subzonal insemination (SUZI; 85
      attempts), on day 0 (egg retrieval and SUZI), day 1 and day 2 (embryo transfer).
      On day 0, the egg and oolemma diameters (mean +/- SD) were 164.0 +/- 19.6 microns
      and 114.2 +/- 16.8 mu 5m respectively. The zona thickness was 17.8 +/- 13.4
      microns and correlated with the oolemma diameter (r = 0.24, p < 0.001). The
      fertilisation rate was significantly lower for the smaller oocytes (less than 108
      microns diameter) compared with the larger oocytes (over 108 microns) (9.8% vs
      21.2% respectively; p < 0.05). There was little variation in oocyte diameter
      according to nuclear status. However, oocyte diameter increased significantly
      between day 0 and day 1 (p < 0.001) for both fertilised and unfertilised oocytes.
      Six different indications for SUZI were investigated in detail: three with non
      specific (normal and subnormal sperm with in vitro fertilization failure,
      oligoasthenospermia) and three with specific sperm defects (flagellar dyskinesia,
      absence of outer dynein arms, antisperm antibodies). Oocytes from the non
      specific defect groups had significantly smaller diameters than the others (p <
      0.05). The mean fertilisation rate was related to the mean oolemma diameter for
      the groups with non-specific sperm defects and the group lacking dynein arms
      (LODA) (r = 0.91, p < 0.05). Eggs from the groups of patients with LODA and those
      with antisperm antibodies had thicker zona pellucida than others (p < 0.05).
      These findings suggest that in addition to nuclear criteria of maturity, the
      growth of oocytes is an important factor for fertilising ability.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582913
TI  - Xenopus interspersed RNA families, Ocr and XR, bind DNA-binding proteins.
AB  - Interspersed RNA makes up two-thirds of cytoplasmic polyadenylated RNA in Xenopus
      and sea urchin eggs. Although it has no known function, previous work has
      suggested that at least one family of interspersed RNA, XR, binds Xenopus oocyte
      proteins, and can influence the rate of translation. We have used two Xenopus
      repeat families, Ocr and XR, to explore their protein binding abilities. Ocr RNA
      binds the same pattern of highly abundant oocyte proteins that XR RNA binds,
      which are believed to be messenger ribonucleoprotein (mRNP) particle proteins. In
      addition, we show that Ocr RNA binds the Oct-60 protein, a member of the POU
      domain family of transcription factors found in Xenopus oocytes. Using a 32 base
      pair sequence from the XR repeat in a DNA affinity column two proteins were
      isolated, 66 kDa and 92 kDa, that together form a complex with XR DNA. One of
      these proteins (92 kDa) also binds XR RNA. We suggest that the role of at least a
      subset of interspersed RNAs in development may be to bind, and sequester in the
      cytoplasm, DNA-binding proteins until the end of oogenesis.

PMID- 7582914
TI  - Genome organisation in the murine sperm nucleus.
AB  - The organisation of DNA sequences in the murine sperm nucleus was studied using
      in situ hybridisation of biotinylated DNA probes. The efficiency of this reaction
      was assessed using a dispersed repetitive DNA probe. Telomeric DNA was
      distributed around the nucleus. Centromeric and ribosomal DNA sequences occupied
      restricted domains in the sperm nucleus. DNA sequences for a transgene and a
      cluster of homeogenes occupied different, and rather less defined, domains.
      Together these results imply that both repetitive and protein-coding sequences
      are arranged in the nucleus in an ordered fashion.

PMID- 7582915
TI  - Expression of the cell cycle control protein cdc25 in cleavage stage bovine
      embryos.
AB  - We have examined the synthesis and expression of a homologue of the cell cycle
      control protein cdc25 by early cleavage stage bovine embryos. cdc25 is the
      protein phosphatase responsible for activating p34cdc2 by dephosphorylating the
      threonine 14 (Thr 14) and tyrosine 15 (Tyr 15) residues of p34cdc2. Human cdc25
      antibody was utilised in western blots and immunoprecipitations to examine the
      presence and synthesis of cdc25 in bovine embryos. cdc25 is present as a 52 kDa
      non-phosphorylated and a 66 kDa presumably phosphorylated form in bovine 1-, 2-,
      4- and 8-cell embryos. However, cdc25 is actively synthesised only in 8-cell
      embryos, indicating that the cdc25 present prior to this stage is inherited from
      the oocyte. In addition, the synthesis of cdc25 was induced in 2-cell embryos in
      which cleavage was blocked with the DNA synthesis inhibitor aphidicolin.

PMID- 7582917
TI  - Highly effective method of human oocyte activation.
AB  - Fresh and aged unfertilised human oocytes were activated by electroporation and
      by exposure to isotonic solution of mannitol supplemented with low concentrations
      of calcium, magnesium and chloride. Over 95% of the fresh oocytes were activated,
      all showing formation of one pronucleus and extrusion of the second polar body.
      Oocytes activated 1 and 2 days post-collection showed activation rates of 66.6%
      and 64.1%, respectively; however, the proportion of one-pronucleate oocytes in
      these groups was significantly lower (61.6% and 23.5%, respectively). There was
      no difference in the activation efficiency between the two activation modes.
      Twelve activated oocytes from the freshly collected group cleaved when left in
      culture. It is concluded that, in the human, a brief exposure to isotonic
      solution of mannitol with low concentrations of calcium, magnesium and chloride
      is a very effective activation stimulus.

PMID- 7582918
TI  - Identification of porcine sperm plasma membrane proteins that may play a role in
      sperm-egg fusion.
AB  - Sperm plasma membrane (PM) proteins that demonstrate affinity for egg PM
      preparations have the potential to be biologically important during sperm-egg
      binding and/or fusion. In this study four such proteins have been identified. To
      provide quantitative evidence for possible biological function, the large natural
      variation among different porcine sperm populations with regard to their ability
      to interact with the egg was compared with the relative binding of egg PM
      material to individual proteins. An aliquot from each of 24 porcine ejaculates
      was evaluated by the zona-free hamster ova bioassay and the remainder processed
      to yield sperm PM vesicles. Aliquots of sperm PM were solubilised, separated by
      SDS-PAGE, western blotted and probed with partially purified, biotinylated egg PM
      protein. Bound egg PM proteins were visualised on western blots by an
      avidin/biotin/horseradish peroxidase system and analysed by scanning laser
      densitometry. Four sperm PM proteins (62, 39, 27 and 7 kDa estimated molecular
      mass) were the predominant binders of egg PM. The amount of egg PM bound to the
      62 kDa protein was significantly correlated with the ability of sperm from the 24
      ejaculates to penetrate zona-free hamster ova (percentage of ova penetrated, p =
      0.01, R = 0.65; number of penetrated sperm per ovum, p = 0.02, R = 0.63).

PMID- 7582919
TI  - The double spermatogenesis in Scutigera coleoptrata (Myriapoda, Chilopoda): macro
      and microspermatocyte growth.
AB  - In Scutigera coleoptrata, double spermatogenesis (macro and micro germinal cells)
      was reinvestigated by means of both image analysis and electron microscopy. Image
      analysis of the two cell-lines showed no differences in DNA content between the
      two types of spermatogenesis. The only difference found, with the exception of
      the size and the related number of organelles, was that in the macro-cell line
      the chromatin was well dispersed and not condensed, which is the opposite of what
      was observed in the micro-cell line. It is assumed that the level of activity
      related to this condensation process is at the origin of the two pathways of
      development.

PMID- 7582916
TI  - Long-lasting exocytosis and massive structural reorganisation in the egg
      periphery during cortical reaction in Platynereis dumerilii (Annelida,
      Polychaeta).
AB  - The course of the cortical reaction in the Platynereis dumerilii egg is described
      from live observation and from sectioned fixed material and is found to differ in
      several aspects from the course of cortical reactions in better-known systems.
      Cortical granules are unusually numerous. They are discharged by exocytosis
      during a period of about 25 min following fertilisation (18 degrees C). Most of
      the surplus membrane material brought to the egg surface by exocytosis is set
      free into the perivitelline space. Swelling of egg jelly precursor secreted by
      cortical granule exocytosis may be causal for the detachment of the vitelline
      envelope from the egg cell surface which, however, remains attached punctately to
      the vitelline envelope by about 30,000 microvilli. Under the strain of the
      distending vitelline envelope, the bases of the microvilli move and line up,
      pulling the cell surface into a network of ridges. The grooves in between the
      ridges are the sites of exocytoses. Cytochalasin B, generally destabilising actin
      filaments, induces rupture of the microvilli and exaggerated distension of the
      vitelline envelope during the cortical reaction. In a final phase of the cortical
      reaction the vitelline envelope wrinkles and falls back onto the egg cell
      surface, the microvilli shorten and the egg cell transiently becomes deformed by
      local contractions. The cortical reaction in the nereid egg is discussed as a
      process of distortion and reorganisation of the egg cortex and plasmalemma. The
      abundance of cortical granules accommodating egg jelly precursor in the
      Platynereis oocyte is attributed to the mode of so-called diffuse oogenesis
      characteristic of nereids, i.e. of differentiation of oocytes freely suspended in
      the coelomic fluid. In nereids, egg jelly therefore forms after fertilisation as
      opposed to ovulation.

PMID- 7582921
TI  - Beakers versus breakers: how fertilisation in the laboratory differs from
      fertilisation in nature.
AB  - The fertilisation of free-spawning invertebrates, mainly sea urchins, has been
      studied extensively during the last hundred years. However, results obtained from
      in vitro experiments do not always reflect what happens in the real world.
      Organisms in their natural habitats have a complex set of challenges, cues and
      behaviours to contend with during fertilisation and early development, factors
      that are normally not considered in the laboratory setting. This review examines
      recent work on fertilisation ecology and discusses the relevance of these results
      to the findings gleaned from laboratory research. Emphasis is placed on stresses
      associated with fertilisation in situ, and how responses to environmental
      stresses (such as from turbulence, oxidative stress, ultraviolet radiation and
      pathogens) might affect the fertilisation process.

PMID- 7582922
TI  - Eurosurgery 95. 5th European Congress of Surgery. Barcelona, Spain, 15-19
      November 1995. Abstracts.

PMID- 7582920
TI  - Control of the surface expression of uvomorulin after activation of mouse
      oocytes.
AB  - Uvomorulin (E-cadherin) is the major cell adhesion molecule responsible for
      intercellular adhesion in early mouse embryos. In contrast to other cell adhesion
      molecules, it is not detectable on the cell surface until around 6 h after
      fertilisation or parthenogenetic activation, at the time when pronuclear
      formation occurs (Clayton, L., Stinchcombe, S.V. and Johnson, M.H., Zygote 1, 333
      44, 1993). In order to investigate this developmental control of surface
      expression of uvomorulin, we examined the effects of inhibitors of various
      cellular processes on the appearance of uvomorulin at the oocyte surface, as
      assessed immunocytochemically. Inhibitors of cytoskeletal assembly (cytochalasin
      D and nocodazole), protein synthesis (puromycin and anisomycin), and DNA
      synthesis (aphidicolin) had no effect on surface expression. Brefeldin A, which
      inhibits intracellular transport and secretion, did prevent surface expression,
      but monensin did not. The effects of brefeldin were reversible; following 8 h of
      treatment, recovery of surface expression after removal of brefeldin began within
      2 h. The time-course of surface expression post-activation suggested a link with
      pronuclear formation. However, when pronuclear formation was advanced
      experimentally using 6-dimethylaminopurine (DMAP), concomitant advancement of
      surface uvomorulin was not observed. Similarly, surface expression of uvomorulin
      did not accompany puromycin-induced pronuclear formation in maturing meiotic
      metaphase 1 (MI) oocytes in vitro. Thus, surface uvomorulin expression does not
      appear to be linked simply to pronuclear formation. Proteolytic processing of
      both newly synthesised and total uvomorulin to generate mature molecule from
      precursor increased within 30 min to 1 h after activation, and also occurred in
      the continued presence of brefeldin, suggesting that uvomorulin processing
      appears to be controlled independently of its surface expression.

PMID- 7582924
TI  - On some electrolytic and water metabolism modifications in rats susceptible to
      audiogenic convulsions.
AB  - Following our research in the relationship between mechanisms of blood
      transportation of sodium and cerebral excitability, we studied adult rats (males
      180-230 gm), divided into two groups according to their level of excitability to
      noise: 1. Rats susceptible to audiogenic convulsions and, 2. Rats with normal
      response to acoustic stimulation. In the two groups we determined the following
      parameters: 1. mechanisms of blood transportation of sodium; 2. general free
      motor behaviour; oriented behaviour (to satisfy motivation for sodium or water);
      nature and intensity of motivation expressed as milliliters of liquid and grams
      of sodium consumed; 3. influence of the variable sodium intake on the renal
      elimination of sodium, potassium and water. Also the influence of the variable
      water intake on the renal elimination of water. Results obtained show that:
      cerebral hyperexcitability manifested as susceptibility to audiogenic convulsions
      is associated with several modifications expressed as follows: 1) Sodium
      transportation in blood serum occurs in a free state in rats susceptible to
      audiogenic convulsions, while in normal rats it occurs in a state of interaction
      with serum proteins; 2) In animals susceptible to audiogenic convulsions one can
      notice significant hypermotricity in the behaviour cage; 3) Hyperexcitable
      animals consume significantly more sodium chloride solution which they freely
      choose, in a motivational manner, than animals with a normal excitability; 4)
      Increased, motivational consumption of sodium chloride is associated with
      increased renal elimination of sodium in animals susceptible to audiogenic
      convulsions. Increased renal elimination of sodium is accompanied by increased
      elimination of water, therefore with the protection of renal concentration
      mechanisms; 5) If we take the Na/K ratio as an indicator for the function of the
      corticosuprarenal and represent it as a function of the sodium intake, the data
      presented show that ratio is greater in animals with cerebral hyperexcitability,
      which is in concordance with the data presented, also involving the
      mineralcorticoid hormones in this response, a similar picture to that of loading
      the body with sodium; 6) The data presented seem to advocate once more for the
      idea that normal cerebral excitability is compatible with the existence of
      mechanisms that transport sodium in a state of oligoenergetic interaction with
      blood proteins.

PMID- 7582923
TI  - [Studies concerning the relaxant effects of the L-arginine-nitric oxide system].

PMID- 7582925
TI  - The influence of some cations on PAF-induced gastric mucosal damage in rats.
AB  - We investigated the influences of Li2CO3 1 g/kg i.p., MgSO4 1 g/kg i.p. and Zinc
      acexamate 100 mg/kg p.o. on gastric lesions induced by Platelet Activating Factor
      (PAF), 2 micrograms/kg i.v. in rats. Our data show that, Li+ has no a significant
      influence, while Mg2+ decrease significantly the PAF induced gastric lesions.

PMID- 7582926
TI  - The influence of an PGF2x analogue and of some peptidoleukotrienes and platelet
      activating factor antagonists in experimentally induced gastric ulcer in rats.
AB  - We tested the influence of 30 mg/kg/per os BN 52021, 300 micrograms/kg
      Cloprostenol (CIPG) and of 5 mg/kg per os LY 171883B in stress restrain and
      indomethacin induced ulcers in rats. The data obtained show that CIPG and LY
      171883 have a significant gastroprotective action in both ulcer models. BN 52021
      has a significant protective activity in stress ulcer and less in indomethacin
      induced ulcers.

PMID- 7582928
TI  - The relation zinc-lipidic peroxidation in experimental diabetes mellitus.
AB  - The authors investigated the influence of Zn upon glycemy and certain REDOX
      parametres within the hepatic tissue. The experiment was performed on young
      Wistar rats with AD, to which Zn sulfate was administered. The values of the
      antioxidating enzymes: cathalasis and peroxidase decrease in the diabetes'
      hepatic tissue. The therapy with Zn remakes their activities and increases
      glutathione synthesis. The Zn protecting effect in lipidic peroxidating process
      also acts upon hepatocyte membrane, fact illustrated by the decrease of LDH in
      the plasma of the animals treated with Zn.

PMID- 7582929
TI  - Study of ejection fraction of professional divers during simulated diving in
      hyperbarism and various respiratory mixture.
AB  - This study was done to elucidate the influence of high pressure (5.5 and
      respectively 20.0 ATA) and various respiratory mixtures (nitrox and heliox) on
      cardiac output investigated (by the Ejection fraction) as in the medical
      literature there have not been found studies on the left ventricular performance
      of the divers under these conditions.

PMID- 7582927
TI  - Experimental studies on human bronchial smooth muscle in vitro.
AB  - The aim of this study was the investigation of bronchial reactivity in human
      bronchial smooth muscle in vitro. In fact, the study has two purposes: to achieve
      the best methods of research on human bronchial strips reactivity in vitro; to
      reveal the effect of acetylcholine and histamine on bronchial smooth muscle; The
      contractile effect of acetylcholine appears at 10(-6) M in the organ-bath; the
      maximal acetylcholine contraction was obtained at 10(-3) M in the organ-bath.
      Histamine induced a maximal contraction at 10(-3) M, but a concentration of 10(
      3) M in the organ bath had no effect.

PMID- 7582930
TI  - Study of heart rate of professional divers in hyperbarism during simulated diving
      in saturation with different respiratory mixture.
AB  - Study of heart rate of professional divers in hyperbarism during simulated diving
      in saturation with different respiratory mixture. Study of heart rate of
      professional divers in hyperbarism (5.5 ATA and 20 ATA) during simulated divings
      and in saturation with different respiratory mixture (nitrox and heliox
      respectively) show a nonsignificant difference in bradycardia response. Results
      have confirmed that bradycardia is not influenced by respiratory gases and the
      depth and is only due to high pressure.

PMID- 7582931
TI  - Reticulin-M, an antianaphylactic peptide secreted by reticulo-endothelial system.
AB  - I. Moldovan (1923) demonstrated in the blood ultrafiltrate from anaphylactically
      prepared guinea pigs, which believed to anaphylactic shock, or which were
      previously injected with coloidal substances as India ink to stimulate the RES,
      an antianaphylactic principle named Reticulin-M(R). Authors extracted R from
      organs rich in RES with acetone, established their, peptidic nature and tested it
      on anaphylactic prepared guinea pig uterine horns in vitro. The peptides were
      fractioned by high voltage paper electrophoresis. The fractions were cut up in
      four groups, eluted and tested. The second basic group was identified as active
      and concentrated by acetone, recipitation. In conclusion several techniques were
      used to obtain, to test, to isolate and to concentrate R, a natural
      antianaphylactic peptidic factor, which may be a cytokine.

PMID- 7582932
TI  - The effect of leucotrofina and BSA (bovine serum albumin) antigen on the
      ontogenetical capacity of antibody generation in chicken.
AB  - Leucotrofina administration to chickens of two different ages (2,5 IU/chicken to
      3 days old chickens, and 5 IU/individual to 21 days old chickens), associated
      with an antigen (1 / 1000 Bovine Serum Albumin) (0,25 ml, respectively 0.5
      ml/animal in young and in older chickens) affected several blood serum parameters
      as: the antibodies concentration, the gamma-globulins, the total proteins, and
      the nitrogen of the free amino-acids content in a manner corresponding to the
      experimental model and to age the of the animals.

PMID- 7582933
TI  - Post-traumatic stress disorders; psychophysiological and medical aspects.
AB  - Post-traumatic stress disorder (PTSD) is a psychobiological concept. Distressing
      events outside the range of usual human experience produce several
      somatovegetative and especially several psychic disturbances. The
      psychoneuroendocrine mechanisms of PTSD concern the impact of cognitive factors,
      a disorder of arousal and alterations of the central sympathoadrenal system and
      of the noradrenergic mediation. The authors exhibited the influence of stressful
      events (uprising of December 1989 in Romania) on the intestinal and noncoronary
      cardiovascular complains and analysed five cases of PTSD, treated in the last
      three years.

PMID- 7582935
TI  - Experimental model of psychic stress.
AB  - An experimental model for the induction of an informational psychic stress in the
      rat, comparable with the psychic stress in man, is described. The method consists
      in the production of the emission of significant acoustic signals by an
      "emitting" group of animals, subjected in an aleatory manner to electroshocks.
      The acoustic nociceptive signals are heard by a "receiving" group of animals. In
      this "receiving" group are studied the behaviour and the neuroendocrine changes.
      This experimental model may be useful for studies of psychopharmacology, for the
      research of psychotropic drugs and for the determination of their action upon the
      harmful effect of informational aggressions and psychic stress.

PMID- 7582934
TI  - The pattern of the electrodermal activity as indicator of stress related
      reaction.
AB  - The aim of the present study was to characterize the patterns of signals
      associated with noninvasively detected skin sudomotor transient reflexes in a
      group of 221 apparently healthy people, aged between 16 and 72 years. By means of
      two pairs of surface electrodes applied respectively to the palm of the hand and
      to the sole of the foot skin impedance changes were recorded as two electrodermal
      parameters: skin electrical resistance and skin electrical capacitance. The
      recordings were obtained under standard conditions initially in the basal resting
      state of the subject and then, after the application of some standardized stimuli
      (evoked electrodermal responses). In terms of the basal (spontaneous)
      electrodermal activity and the evoked responses the subjects were divided into
      three categories: I--those with a high threshold of sympathetic activation (quiet
      basal trace and ample evoked responses); II--those with a medium threshold for
      sympathetic activation (basal trace with some spontaneous electrodermal activity,
      but obviously of a lower amplitude than the evoked responses); III--those with a
      low threshold for sympathetic activation (a tracing showing frequent, larger
      spontaneous sympathetic discharges from which the evoked responses cannot be
      distinguished). Of the 221 subjects, 22.2% in group I, 69.2% were included in
      group II, and 8.6% in group III. Our data show that each individual presents a
      characteristic electrodermal pattern which expresses the degree of
      stability/instability of the sympathetic nervous system, the most sensitive
      component of the physiological stress reaction system.

PMID- 7582936
TI  - Analysis of psychophysiological mechanism with cardiovascular risks.
AB  - The review summarises newer findings on the relations between personality and
      behavioural traits and the risk factors for coronary heart disease (CHD). After a
      critical analysis of the type of A behavioural pattern (TABP), the role of
      hostility as a crucial element of this behaviour is underlined. Emphasis is put
      on the cardiovascular overarousal on the psychophysiological mechanisms of TABP
      and on the relationship proved by the authors too, between TABP and diseases
      other than CHD. It appears justified to consider TABP rather as a "disease prone
      behaviour" especially among stress vulnerable subjects.

PMID- 7582937
TI  - Lithium and anti-viral drug toxicity: II. Further studies on the ability of
      lithium to modulate the hematopoietic toxicity associated with the anti-viral
      drug zidovudine (AZT).
AB  - Lithium is an agent capable of influencing many aspects of blood cell production,
      in particular, the formation of granulocytes. Because of this property, lithium
      has been demonstrated to be an effective agent whenever granulocyte production is
      either faulty or inadequate. The anti-viral drug zidovudine (AZT) has used been
      extensively in the treatment of acquired immune deficiency syndrome (AIDS).
      However, its effectiveness is limited because of the myelosuppression and bone
      marrow toxicity associated with its use. We have previously demonstrated that
      lithium, when combined with AZT in vitro with normal bone marrow cells or when
      administered in vivo to mice receiving dose-escalation AZT, reduced the
      myelosuppression and marrow toxicity of AZT significantly. We report here further
      studies designed to evaluate the extent of lithium's capacity to modulate AZT
      toxicity by investigating the ability of lithium to influence blood cell
      production when administered to normal mice during an initial exposure to AZT.
      C57BL6 were administered dose-escalation AZT (1.0 mg/ml and 2.5 mg/ml) for a
      period of 4-weeks in the presence or absence of lithium carbonate (1 mM). This
      was followed by an additional 4-week period during which mice received only AZT.
      Animals were analyzed on a weekly basis for their peripheral blood indices.
      Animals receiving dose-escalation AZT demonstrated anemia, thrombocytopenia, and
      neutropenia which was dose-related. During the period when animals received
      combination lithium/AZT, there was significantly less anemia, thrombocytopenia,
      and neutropenia as compared to the AZT controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582938
TI  - Endogenous opioid abstinence syndrome.
AB  - Starting from the observation that an increase of stress analgesia is followed by
      a hyperalgesia period, with a series of symptoms characteristic of the exogenous
      opioid abstinence syndrome (EXOAS), the authors supposed also the possibility of
      the existence of an endogenous abstinence syndrome (ENOAS). In order to
      demonstrate the existence of this syndrome, they investigated at first the
      possibility of the appearance of an acute tolerance to opioids. Then they
      followed-up the course of behaviour during and after informational stress in
      untreated animals, in animals treated with naloxone, which--being an antagonist
      of opioids--can induce EXOAS in toxicomaniacs, and in animals treated with
      clonidine and propranolol, that are used in the treatment of EXOAS. Experimental
      researches have demonstrated the possibility of ENOAS occurrence, its aggravation
      by naloxone and its improvement with clonidine and propranolol.

PMID- 7582939
TI  - The effects of hydrocortisone-acetate on some biochemical parameters in the
      liver, thymus, thymocytes and adrenals of white Wistar rats.
AB  - The administration of hydrocortisone-acetate to adult Wistar rats induced
      emphasized biochemical modifications in the thymus, together with the weight
      decrease of the gland. Liver was less affected and adrenal's function was
      suppressed, as shown by the increase of the ascorbic acid content. The treatment
      did not induce a stress situation.

PMID- 7582940
TI  - CC-1065 CBI analogs: an example of enhancement of DNA alkylation efficiency
      through introduction of stabilizing electrostatic interactions.
AB  - The three trimethylammonium salts 3-5 proved to be 100 times more efficient at
      alkylating DNA than 2 and exhibited DNA alkylation efficiencies identical to that
      of (+)-CC-1065 (1). In addition, the agents 3 and 4 exhibited DNA alkylation
      selectivities identical to that of 2. This may be attributed to spatially well
      defined stabilizing electrostatic interactions between the positively charged
      trimethylammonium salt lying on the peripheral face of the agents and the
      bracketing, negatively charged phosphates located in the DNA backbone that
      enhance the DNA noncovalent binding affinity without affecting DNA binding or
      alkylation selectivity. The agent 5 exhibited an altered and more discriminating
      AT-rich adenine N3 alkylation selectivity than 2-4 that may be attributed to the
      groove placement of the large trimethylammonium salt.

PMID- 7582941
TI  - Novel cytotoxic DNA sequence and minor groove targeted photosensitizers:
      conjugates of pyrene and netropsin analogues.
AB  - The design, syntheses, photochemical and biological properties of conjugates of
      pyrene with pyrrole- (1) and imidazole-containing (2) analogues of netropsin are
      reported. The results of an ethidium displacement assay and circular dichroism
      (CD) titration studies show both compounds bind with a higher affinity to poly(dA
      dT) than to poly(dG-dC). In addition they bind as strongly to T4 coliphage DNA as
      to calf thymus DNA suggesting the binding occurs in the minor groove. The
      quenching rate constants of the singlet excited states of agents 1 and 2 by
      molecular oxygen were found to be 8.5 x 10(9) M-1S-1 and 7.7 x 10(9) M-1S-1,
      suggesting the involvement of singlet oxygen. Both compounds showed some
      cytotoxicity to human chronic myeloid leukemia K562 cells in the dark. Upon
      irradiation the activities were significantly enhanced resulting in photoinduced
      dose modifications of 8 and 14 for 1 and 2, respectively under the conditions
      employed. Both agents were markedly more phototoxic than 1-pyrenebutyric acid 8.
      To address the mechanism of action of compounds 1 and 2 their photoactivated
      abilities to produce DNA strand breaks were measured. Both agents caused
      increased single strand breakage with increasing UV exposure. The concentrations
      (EC50) of 1 and 2 needed to cause 50% single-strand cleavage of pBR322 DNA upon
      UV-A activation were found to be 40 microM and 45 microM, respectively. In
      contrast, no DNA strand breaks were observed in the dark with either conjugate or
      with 8 following irradiation. DNA strand breaks were measured in drug treated
      K562 cells using alkaline elution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582942
TI  - NMR structure of d(CGCA3T3GCG)2:tren-microgonotropen-b:Zn(II) complex and
      solution studies of metal ion complexes of tren-microgonotropen-b interacting
      with DNA.
AB  - The solution structure of a 1:1 complex of zinc tren-microgonotropen-b
      [6b:Zn(II)] with d(CGCAAATTTGCG)2 has been determined by 2D nuclear Overhauser
      effect 1H NMR spectroscopy and restrained molecular modeling. The exchangeable
      and nonexchangeable proton resonances of d(CGCA3T3GCG)2:6b:Zn(II) indicate that
      the Zn(II) is interacting in the A+T-rich region of the dsDNA and the tren region
      of 6b, while 31P NMR shows interaction of the Zn(II) with the phosphate backbone.
      Proton chemical shift differences between d(CGCA3T3GCG)2:6b:Zn(II) and
      d(CGCA3T3GCG)2:6b are in agreement with the polyamino substituent of 6b [
      (CH2)4N(CH2CH2)N-(CH2CH2NH2)2] forming a four-coordinated Zn(II) complex similar
      to that found in the X-ray structure of 'tren-chloride':Zn(II). The P9 and P10
      phosphate oxygens that are held by hydrogen bonding to the tren substituent of 6b
      in the DNA:6b complex become ligands to the tren-complexed Zn(II) in
      DNA:6b:Zn(II). To do so there is a 2 A decrease in the adjacent phosphate-to
      phosphate distance at the Zn(II) binding site. This motion brings about an
      increased bend of 14.6 degrees in the helical axis of d(CGCA3T3GCG)2:6b:Zn(II)
      compared to that found in d(CGCA3T3GCG)2:6b. Single stranded cleavage of linear
      DNA fragments was not observed in the presence of 6b and Fe(II), Co(II), Ni(II),
      Cu(II), Zn(II), La(III) or Ce(III); this is likely due to the metal ion being
      sequestered as in the structure of d(CGCA3T3GCG)2:6b:Zn(II) complex. Supercoiled
      DNA was susceptible to cleavage by 6b:Cu(II) in the presence of O2 and a reducing
      agent.

PMID- 7582943
TI  - Design, synthesis and sequence selective DNA cleavage of functional models of
      bleomycin--II. 1,2-trans-disubstituted cyclopropane units as novel linkers.
AB  - The design and syntheses of functional models for bleomycin in which AMPHIS, a
      simplified model of the metal-chelating subunit of bleomycin is connected to
      distamycin analogs with a series of linkers, are described. Kinetic studies and
      DNA cleavage assay show that 1,2-trans-disubstituted cyclopropane units are the
      best linkers within this series. Study of selective DNA cleavage on high
      resolution polyacrylamide sequencing gels indicates that the linker modified
      hybrids generally cleave selectively at the 5' end of poly T sites and at the 3'
      end of poly A sites. Cleavage activity is enhanced for most of the compounds
      related to those with shorter linkers, previously reported, (Huang, L.; Quada, Jr
      J. C.; Lown, J. W. Bioconjugate Chem. 1995, 6, 21, Ref. 1) probably as a result
      of the linker allowing the active complex to approach the target deoxyribose more
      closely and efficiently. Certain of the compounds, ones containing a (S)-methyl
      in the linker and the (S,S)-cyclopropyl linker, exhibit unique cleavage sites,
      indicating that these linkers allow the hybrids to locate novel, individual DNA
      binding sites.

PMID- 7582944
TI  - DNA-DNA interstrand cross-linking by cis-diamminedichloroplatinum(II): N7(dG)-to
      N7(dG) cross-linking at 5'-d(GC) in synthetic oligonucleotides.
AB  - The nucleotide sequence specificity of the DNA-DNA interstrand cross-linking
      reaction of cis-diamminedichloroplatinum(II) (cis-DDP) was studied in synthetic
      oligonucleotides. Of six self-complementary DNAs tested, only those containing
      the central sequence 5'-d(GC) formed appreciable interstrand cross-linked
      product, as assayed by denaturing polyacrylamide gel electrophoresis (DPAGE). The
      nucleotide connectivity of the interstrand cross-link was defined by sequence
      random oxidative fragmentation followed by DPAGE, revealing that dG residues on
      opposite strands at the sequence 5'-d(GC) were connected to one another. The
      covalent structure of the cross-link was established following hydrolysis of the
      phosphodiester backbone of a structurally homogeneous sample of a cis-DDP
      interstrand cross-linked DNA tetradecamer. HPLC analysis of the hydrolysate
      returned all of the deoxynucleoside residues from the starting DNA except for two
      deoxyguanosine residues. Also returned was diammine-bis-[N7-(2'-
      deoxyguanosyl)]platinum(II)2+, identified by a combination of spectroscopic
      methods, and comparison to a synthetic authentic sample. This study directly
      establishes that cis-DDP forms interstrand cross-links at the duplex sequence 5'
      d(GC), linking deoxyguanosine residues on opposite strands at N7 through a
      bridging platinum atom. Computer simulation of the interstrand cross-linked
      product using molecular mechanics energy minimization and molecular dynamics
      revealed significant structural reorganization at the site of the cross-link
      including a ca 40 degrees angle between the platinated guaninyl residues, which
      propagated to adjacent residues by base stacking to yield duplexes bent by some
      30 degrees toward the major groove.

PMID- 7582946
TI  - Synthesis, DNA interactions and biological activity of DNA minor groove targeted
      polybenzamide-linked nitrogen mustards.
AB  - A series of polybenzamide DNA minor groove binding ligands bearing either one or
      two monofunctional mustards have been synthesised, and their cytotoxicities and
      interactions with DNA have been studied. Analogues with two alkylating functions
      (e.g. compounds 7 and 14) are the most cytotoxic, with 7 being 1000-fold more
      potent than the clinical mustard chlorambucil against P388 leukemia in culture,
      as well as being more potent in vivo. Monofunctional analogues were also
      significantly more cytotoxic than chlorambucil, despite bearing much less
      reactive mustard species. These results support the concept that targeting
      nitrogen mustard alkylating agents to DNA by attachment to DNA-affinic carriers
      can greatly enhance cytotoxicity due to alkylation, and that even for such DNA
      targeted mustards, crosslinking is a more toxic event than monoalkylation. Close
      analogues of 7 differing only in their radius of curvature, appear to alkylate
      and crosslink DNA in similar fashion, yet have widely differing cytotoxicities.
      The most cytotoxic compound (7) possesses a geometry most complementary to that
      of duplex DNA, suggesting that the most toxic lesions are those which result in
      least DNA distortion, thus being less easily recognised by DNA repair systems.

PMID- 7582945
TI  - Perturbations in DNA structure upon interaction with porphyrins revealed by
      chemical probes, DNA footprinting and molecular modelling.
AB  - The interactions of several porphyrins with a 74 base-pair DNA sequence have been
      examined by footprinting and chemical protection methods. Tetra-(4-N-methyl
      (pyridyl)) porphyrin (TMPy), two of its metal complexes and tetra-(4
      trimethylanilinium) porphyrin (TMAP) bind to closely similar AT-rich sequences.
      The three TMPy ligands produce modest changes in DNA structure and base
      accessibility on binding, in contrast to the large-scale conformational changes
      observed with TMAP. Molecular modelling studies have been performed on TMPy and
      TMAP bound in the AT-rich minor groove of an oligonucleotide. These have shown
      that significant structural change is needed to accommodate the bulky trimethyl
      substituent groups of TMAP, in contrast to the facile minor groove fit of TMPy.

PMID- 7582948
TI  - Intercalative interactions of ethidium dyes with triplex structures.
AB  - The binding of phenanthridine dyes to triplex poly(dT)*poly(dA).poly(dT) and its
      precursor duplex poly(dA).poly(dT) is characterized using linear dichroism and
      circular dichroism spectroscopy, and thermal denaturation. The two monomeric dyes
      ethidium bromide and propidium iodide are shown to behave similarly to each other
      in intercalating into and stabilizing both the duplex and the triplex structures.
      However, contrary to expectations, the extra cationic side-chain of propidium
      iodide provides no significant extra stabilization of triplex compared with
      ethidium bromide, although propidium does stabilize the duplex more than
      ethidium. The monomeric dyes appear to have somewhat different binding geometries
      with the duplex and triplex polymers. The dimeric dye ethidium homodimer is found
      to bis-intercalate in the triplex as well as the duplex but, in contrast to the
      monomers, no variation in geometry between duplex and triplex is observed.
      However, although dimer stabilizes the duplex, it has no effect on the thermal
      stability of the triplex. This lack of binding preferentiality of the dimer for
      triplex compared with the monomeric dyes indicates greater constraints on the
      accommodation of a bis-intercalator in the triplex structure than in the duplex.

PMID- 7582949
TI  - Binding and cleavage characteristics of the complexes formed between the
      neocarzinostatin chromophore and single site containing oligonucleotides.
AB  - It is shown by fluorescence spectroscopy that the post-activated form of
      neocarzinostatin chromophore (NCSi-glu) can form stable complexes with single
      site oligonucleotides (SSOs) featuring sequences known to be involved in double
      stranded (AGC.GCT, AGT.ACT, AGA.TCT, ACA.TGT) or single stranded (AGG.CCT)
      cleavage (attacked residues in bold). Furthermore, the same SSOs form cleavage
      productive complexes with native neocarzinostatin chromophore (NCS chrom) over a
      similar concentration range. The productive complexes yield damage similar to
      that observed if the same sequence is part of a longer DNA piece. Previously
      identified double stranded site sequences ATT.AAT and TAT.ATA are shown to
      contain overlapping attack sites. Binding order preference derived from
      fluorescence quenching experiments for NCSi-glu is consistent with constants
      derived by quantitative cleavage affinity binding experiments with NCS chrom.
      This confirms the similarity in interactions between the NCSi-glu and NCS chrom
      and justifies the use of NCSi-glu as a stable analog of NCS chrom.

PMID- 7582950
TI  - Criteria for the mode of binding of DNA binding agents.
AB  - A complete characterization of DNA binding agents requires that their mode of
      binding to DNA be established. In the absence of high resolution structural data,
      the mode of binding is, of necessity, usually inferred indirectly from various
      solution studies. The purpose of this study is to show that only certain methods
      can be used reliably to infer the DNA binding mode. Comparative fluorescence and
      hydrodynamic studies using the proven intercalator ethidium and the groove binder
      Hoechst 33258 are described. The results of our studies show that while
      fluorescence intensity, polarization, and quenching measurements can detect a
      binding interaction of the ligand with DNA, none are sensitive indicators of the
      binding mode. Fluorescence contact energy transfer studies can reliably indicate
      intercalation, as can viscosity measurements. Our results illustrate reliable
      criteria that may be used to distinguish intercalation from groove binding in the
      absence of high resolution structural data.

PMID- 7582952
TI  - Synthesis and properties of a Hoechst-like minor-groove binding agent tethered to
      an oligodeoxynucleotide.
AB  - A small Hoechst-like DNA groove-binding fluorophore carrying a terminal
      bromoacetimido linker has been synthesized. Individual diastereomeric
      oligodeoxynucleotide dodecamers containing a thiol-based linker attached to an
      internucleotide phosphoramidate within a sequence of dA-dT residues were each
      covalently labeled with the new fluorophore. One isomer of the DNA-fluorophore
      conjugate (Isomer B) hybridizes to the complementary single-stranded target DNA
      and the presence of the tethered fluorophore results in both increased duplex
      stability and an enhanced fluorescent signal, presumably due to the fluorophore
      binding in the dA-dT rich minor groove. Duplex stability is increased by 2-3
      degrees C and the fluorescence quantum yield for the fluorophore increases four
      fold. In contrast, the other diastereomer (Isomer A) exhibits reduced helix
      stability (approximately 2 degrees C) and only slight changes in fluorescence
      intensity upon hybridization.

PMID- 7582951
TI  - New insights into calicheamicin-DNA interactions derived from a model nucleosome
      system.
AB  - Using the Xenopus borealis 5S RNA gene, we have identified several new features
      of the interaction of calicheamicin (CAL), an enediyne antitumor agent, with
      nucleosomal and naked DNA targets. CAL-mediated DNA damage was generally reduced
      by incorporation of the DNA into a nucleosome. However, in one instance, the
      frequency of DNA damage was enhanced in the nucleosome compared to naked DNA.
      This increase in CAL damage may result from bending-induced changes in the target
      site, while the association of histone proteins with DNA in the nucleosome may
      generally reduce the affinity of CAL for its targets by imposing dynamic
      constraints on the DNA, by altering target structure, or by steric hindrance. One
      implication of these observations is that new structural features created by
      incorporation of DNA into chromatin may produce 'hot spots' for CAL-mediated DNA
      damage not apparent in naked DNA studies. In a second set of experiments, the
      orientation of CAL at damage sites in naked 5S rDNA was determined. The results
      suggest that minor groove width per se is not a major determinant of CAL target
      selection. Our studies support the generality of an oligopurine recognition
      element, with the additional requirement that the purine tract is interrupted at
      the 3'-end by a pyrimidine(s). To account for these observations, we propose a
      model in which CAL recognizes the unique structural and dynamic features
      associated with the 3'-end of an oligopurine tract. Finally, we conclude that the
      dyad axis of pseudosymmetry of the 5S rRNA gene nucleosome cannot be determined
      with any degree of certainty. This places significant limitations on the
      interpretation of results from the study of drug-DNA interactions with
      reconstituted nucleosomes.

PMID- 7582947
TI  - Asymmetry and dynamics in bis-intercalated DNA.
AB  - The bis-intercalator ditercalinium (NSC 366241), composed of two 7 H
      pyridocarbazoles linked by a bis(ethylpiperidinium), binds to DNA with a binding
      constant greater than 10(7) M-1. One distinctive aspect of the 3-D X-ray
      structure of a DNA-ditercalinium complex is its asymmetry. We propose here that
      the activity of ditercalinium may be related to structural polymorphism and
      dynamic conversion between conformers. It was previously reported that activity
      is closely related to linker composition. Activity increases with increasing
      conformational restraints of the linker. We suggest these conformational
      restraints can lead to asymmetry in DNA complexes and that this asymmetry results
      directly in structural polymorphism. Using the Cambridge Structural Database
      (CSD) as a source of information about chemical fragments that are analogous to
      the linker of ditercalinium, we have explored the conformational space available
      to ditercalinium. The results indicate that the linker is highly constrained and
      that the DNA complex is intrinsically asymmetric. We propose a reasonable
      mechanism of ring reversal that is consistent with the conformations of analogous
      fragments within the CSD.

PMID- 7582953
TI  - Thermodynamic investigation of the association of ethidium, propidium and bis
      ethidium to DNA hairpins.
AB  - We have used a combination of calorimetric and spectroscopic techniques to
      investigate the association of the bis-intercalator ethidium homodimer (bis
      ethidium) to short DNA hairpins with sequences: d(GCGCT5GCGC) and d(CGCGT5CGCG).
      The helix-coil transition of each hairpin, investigated by UV and calorimetric
      melting protocol, takes place in monomolecular two-state transitions with
      characteristic enthalpies of approximately 37 kcal mol-1 for disrupting the four
      dG-dC base pairs of the hairpin stems. Deconvolution of the bis-ethidium-hairpin
      calorimetric titration curves indicate that each hairpin contains two distinct
      binding sites for the ligand: a high affinity site in the stem (Kb approximately
      10(7)) that accommodates one bis-ethidium molecule and a lower affinity site (Kb
      approximately 10(6)) located probably at the loop that accommodates two bis
      ethidium molecules. The overall stoichiometries of three ligands per hairpin are
      in agreement with those obtained in continuous variation experiments using
      visible spectroscopy. The interaction of bis-ethidium for each type of sites
      results in enthalpy driven reactions, with average binding enthalpies, delta Hb,
      of -13.1 and -12.1 kcal mol-1 for the stem and loop sites, respectively.
      Comparison to the thermodynamic profiles of ethidium and propidium binding
      reveals that the bis-ethidium binding to the stem site of each hairpin has a more
      favorable free energy term of -1.4 kcal mol-1 and more favorable enthalpy of -4.2
      kcal mol-1. These suggest that only one phenanthridine ring of bis-ethidium
      intercalates in the stem, while the second planar ring is exposed to solvent or
      weakly associated to the surface of DNA.

PMID- 7582954
TI  - CBI-CDPBO1 and CBI-CDPBI1: CC-1065 analogs containing deep-seated modifications
      in the DNA binding subunit.
AB  - The synthesis and preliminary examination of CBI-CDPBO1 (2) and CBI-CDPBI1 (3),
      CBI analogs of CC-1065 (1) and the duocarmycins incorporating the 3-carbamoyl-1,2
      dihydro-3H-pyrrolo[3,2-e]benzoxazole-7-carboxylate (CDPBO) and 3-carbamoyl-1,2
      dihydro-3H-pyrrolo[3,2-e]benzimidazole-7-carboxylate (CDPBI) DNA binding
      subunits, are detailed. The agents contain deep-seated modifications in the DNA
      binding subunits of the natural products with incorporation of a nitrogen capable
      of functioning as a hydrogen bond acceptor (CDPBO, CDPBI) or hydrogen bond donor
      (CDPBI) on their inside concave face which is in intimate contact with the minor
      groove floor. The CDPBO subunit was prepared through use of a novel and effective
      MnO2-mediated oxidative coupling of 2-(benzyloxy)ethylamine with 5-hydroxyindole
      (4) to directly provide 2-[(benzyloxy)methyl]pyrrolo[3,2-e]benzoxazole (6, 48%)
      in a reaction cascade that initially proceeds with amine regioselective C4
      nucleophilic addition to the in situ generated p-quinone monoimine 13. Subsequent
      conversion of 6 to 8 (debenzylation; MnO2-NaCN, CH3OH) and selective reduction of
      the fused pyrrole (Et3SiH-CF3CO2H) completed the synthesis of the 1,2-dihydro-3H
      pyrrolo[3,2-e]benzoxazole-7-carboxylate ring system. The CDPBI subunit was
      prepared through selective C4 nitration of 22 followed by reduction of the nitro
      group and acid-catalyzed closure to the corresponding 2
      [(benzyloxy)methyl]pyrrolo[3,2-e]benzimidazole 25. The final conversion of 25 to
      the 1,2-dihydro-3H-pyrrolo[3,2-e]benzimidazole-7-carboxylate ring system (CDPBI)
      followed the same protocols introduced for CDPBO. The DNA alkylation efficiencies
      of 2 and 3 were identical and both were substantially diminished relative to that
      of CBI-CDPI1 (40). Thus, the introduction of a single nitrogen atom in the DNA
      binding subunit of 40 has a pronounced and detrimental effect on the relative
      efficiency (100 x) of DNA alkylation. Consistent with these observations, the in
      vitro cytotoxic activity of (+)-2 and (+)-3 were comparable (IC50 = 200 pM,
      L1210) and 40 x less potent than (+)-40 (IC50 = 5 pM, L1210). In contrast to the
      large impact these small structural changes had on the efficiency of DNA
      alkylation, the selectivity of DNA alkylation by 2 and 3 was unperturbed and both
      agents were found to alkylate the same major sites as CBI-CDPI1 (40). The
      potential origin of these effects is discussed.

PMID- 7582955
TI  - Sequence-specific DNA binding by covalently constrained peptide dimers of the
      basic leucine zipper protein GCN4.
AB  - DNA binding of covalently bonded peptide dimers was studied by using enantiomeric
      and C2-symmetric templates as a dimerization module. Amino acid sequence of the
      peptide is derived from that of DNA contact region of the basic leucine zipper
      protein GCN4. These peptide dimers were designed to possess different constraints
      with respect to the orientation of two peptides. The basic region peptides were
      covalently linked to the enantiomeric template at the C-terminal ends. Two
      peptides are arranged either in a right-handed or left-handed geometry depending
      on the chirality of the template. The GCN4 basic region dimers with both right
      handed and left-handed geometries show equal affinity to the native GCN4 binding
      DNA sequences, 5'-ATGACTCAT-3' and 5'-ATGACGTCAT-3', as revealed by the gel
      mobility shift assay. Specific recognition of the palindromic DNA sequence by the
      peptide dimers was confirmed by the DNase I footprinting. Circular dichroism
      spectroscopic study indicates that the basic region peptides bound the target DNA
      sequence in a helical conformation. The degree to which a chiral constraint
      effects may depend on the geometry of two DNA binding domains in the parent
      protein-DNA complex and on a position to apply the chiral constraint.

PMID- 7582956
TI  - Small changes in cationic substituents of diphenylfuran derivatives have major
      effects on the binding affinity and the binding mode with RNA helical duplexes.
AB  - The interactions of dicationic, 2-4, and tetracationic, 5-7, diphenylfuran
      analogs of 1 (furamidine) with RNA have been analyzed by thermal melting,
      spectroscopic, viscometric, kinetic and molecular-modeling techniques. The
      results of these studies indicate that most of the furan derivatives bind to RNA
      duplexes by intercalation in contrast to their minor-groove binding mode in AT
      sequences of DNA, but similar to their binding mode in GC rich regions of DNA.
      The highest affinity for RNA is found for an imidazoline dication, 2. With some
      substituents which inhibit formation of a strong intercalation complex, the
      results suggest a non-intercalative type of binding occurs. The non-intercalative
      binding probably occurs through a complex with the furan derivative bound in the
      narrow, deep major groove of A-form RNA helices.

PMID- 7582957
TI  - NMR studies of the post-activated neocarzinostatin chromophore-DNA complex.
      Conformational changes induced in drug and DNA.
AB  - The glutathione post-activated neocarzinostatin chromophore (NCSi-glu)-DNA
      complex was studied in detail by 2-D NMR spectroscopy. The complex is a model for
      understanding the sequence specific cleavage of DNA by the native
      neocarzinostatin chromophore (NCS chrom), a highly potent enediyne antitumor
      agent. NMR spectral analysis is presented for the free NCSi-glu, the free DNA
      duplex and the NCSi-glu-DNA complex. In addition to the previously reported
      structural details of the complex (Gao, X.; Stassinopoulos, A.; Rice, J. S.;
      Goldberg, I. H. Biochemistry 1995, 34, 40), we demonstrate that the binding of
      NCSi-glu in minor groove results in a patch of negatively charged surface
      covering the otherwise relatively neutral minor groove. The formation of the
      complex is largely driven by hydrophobic forces and the solvation of the polar
      surface of the complex. Comparison of the conformations of NCSi-glu and DNA
      duplex in their free and bound form reveals an induced mutual fit of DNA and NCSi
      glu upon complex formation. The reduced NCS chrom represents a DNA binding motif
      for sequence specific recognition of DNA via intercalation and minor groove
      interactions.

PMID- 7582958
TI  - An efficient route to N6 deoxyadenosine adducts of diol epoxides of carcinogenic
      polycyclic aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons are metabolized to a wide variety of oxidized
      derivatives, including highly reactive diol epoxides which alkylate DNA. The
      reaction lacks regio- or stereospecificity but occurs primarily at the exocyclic
      amino groups of deoxyguanosine and deoxyadenosine. An efficient route to N6
      adducts of deoxyadenosine is described using as examples those arising from trans
      opening of the anti-tetrahydrodiol epoxides of naphthalene, benzo[a]pyrene, and
      benzo[c]phenanthrene. The adducts were synthesized in 50-92% yields by reaction
      of 6-fluoropurine 2'-deoxyriboside with aminotriols formed by trans opening of
      racemic dihydrodiol epoxides using liquid NH3. The diastereomeric adducts were
      separated by HPLC and their absolute configurations were assigned by circular
      dichroism. 1H NMR studies revealed significant differences in conformation of the
      tetrahydroaromatic ring between the sterically unrestricted naphthalene
      derivative and the sterically congested derivatives of benzo[a]pyrene and
      benzo[c]phenanthrene. These differences may have a bearing on the higher
      carcinogenicity shown by the latter hydrocarbons. Undecadeoxyoligonucleotides
      bearing regio- and stereochemically defined adenine N6-anti-trans-benzo[a]pyrene
      adducts have been prepared.

PMID- 7582959
TI  - Synthesis and DNA binding properties of C3-, C12-, and C24-substituted amino
      steroids derived from bile acids.
AB  - Seven new amino- and guanidino-substituted steroids have been synthesized from
      bile acid precursors, either deoxycholic acid or lithocholic acid. Their DNA
      binding properties have been examined using an ethidium displacement assay,
      through studies of hyperchromicity and thermal denaturation, and by circular
      dichroism. Comparison is made to simple aliphatic polyamines such as putrescine,
      1,12-diaminododecane, spermidine, and spermine.

PMID- 7582960
TI  - Enediyne-mediated cleavage of RNA.
AB  - RNA cleavage by enediyne anticancer antibiotics was shown to occur with no
      apparent sequence selectivity, but RNA structure appears to be important in those
      substrates where cleavage was observed. Neocarzinostatin (NCS) cleaved a wider
      variety of RNA substrates than either esperamicin (ESP) or calicheamicin (CAL),
      and dynemicin (DYN) has yet to cleave any RNA substrate tried. NCS, ESP, and CAL
      were all observed to cleave RNA substrates near the 5'-end, and all three
      compounds exhibited cleavage in single-stranded loop regions of the RNA
      substrates. NCS required no thiol for activation and subsequent cleavage, but ESP
      and CAL required addition of thiol, as expected, for cleavage to occur. An RNA
      hairpin substrate containing a UCCU sequence, equivalent to the TCCT sequence
      preferred by CAL in double-stranded DNA substrates, was cleaved by CAL, but no
      retention of selectivity for the UCCU site was retained by CAL in this RNA
      substrate. This study confirms an earlier observation that RNA is a substrate for
      enediyne cleavage, and indicates that nucleic acid cleaving compounds such as the
      enediynes could be useful probes of RNA three-dimensional structure.

PMID- 7582962
TI  - Multiple DNA binding modes of anthracene-9-carbonyl-N1-spermine.
AB  - The poly(dAdT)2 complex of anthracene-9-carbonyl-N1-spermine, a spermine
      derivative terminally substituted with an anthracene moiety, has been studied
      using fluorescence, linear dichroism, circular dichroism, normal absorption
      spectroscopy (as a function of temperature) and computer modelling. For
      comparison, some data are also provided for the same ligand with poly(dGdC)2 and
      calf thymus DNA. Following detailed fluorescence and CD spectroscopic studies, we
      propose that anthracene-9-carbonyl-N1-spermine intercalates in at least two
      different binding orientations with poly(dAdT)2. Based on computer simulation
      data, we deduce that the ligand can intercalate from both the minor groove and
      the major groove. In contrast, intercalation with poly(dGdC)2 probably occurs
      only from the major groove. At high ligand concentrations, the CD spectra suggest
      anthracene-anthracene interactions, whilst the LD data point towards a groove
      bound anthracene. Again from computer simulations, we propose binding modes
      consistent with these observations. Other data from the LD spectra suggest a
      sequential nature to the binding of the ligand to calf thymus DNA, with GC-rich
      sites being occupied first. At low ligand concentrations, anthracene-9-carbonyl
      N1-spermine is able to stabilize poly(dAdT)2 against thermal decomposition, but
      not as effectively as spermine. The reverse is found to be true with calf thymus
      DNA. Both the anthracene-9-carbonyl-N1-spermine and spermine complexes of
      poly(dAdT)2 show pre-melt transitions in their melting curves. The anthracene-9
      carbonyl-N1-spermine complex with poly(dAdT)2 also shows a post-melt transition.

PMID- 7582961
TI  - Selective recognition of the m5CpG dinucleotide sequence in DNA by mitomycin C
      for alkylation and cross-linking.
AB  - The clinically used natural antitumor agent mitomycin C (MC) is known to alkylate
      DNA monofunctionally and bifunctionally, resulting in the cross-linking of DNA.
      These reactions occur selectively with guanines at the CpG sequence. We show,
      confirming a previous report (Millard, J. T.; Beachy, T. M. Biochemistry 1993,
      32, 12850) that cross-linking in oligonucleotides is further enhanced when the
      cytosines in CpG.CpG are 5-methylated to m5CpG.m5CpG. It is shown, furthermore,
      that guanines in m5CpG are monoalkylated two- to three-times faster than in CpG
      indicating that the m5C-induced rate enhancement occurs at the first,
      monoalkylation step of the two-step cross-linking process. The same MC-DNA
      adducts are formed in methylated as in non-methylated DNA. The basepaired but not
      the 5'-flanking, m5C residue is responsible for the enhanced alkylation of
      guanine. Enzymatically activated or Na2S2O4-activated MC shows identical rate
      enhancement of alkylation at m5CpG. pBR322 DNA methylated by CpG-methylase was
      cross-linked two- to three-times more efficiently by MC than non-methylated DNA,
      indicating that the m5C effect is not an artifact of oligonucleotides. An
      electronic effect of the 5-methyl group of cytosine transmitted via G.C H-bonding
      to N2 of guanine is suggested as responsible for increased reactivity with MC.
      CpG is severely depleted in mammalian DNA and it is speculated that this factor
      attenuates MC cytotoxicity in human cells.

PMID- 7582966
TI  - A urinary metabolite of delta 1-tetrahydrocannabinol. The first synthesis of
      4",5"-bisnor-delta 1-tetrahydrocannabinol-7,3"-dioic acid, and a deuterium
      labelled analogue.
AB  - The first synthesis of unlabelled and [2H5]-labelled 4",5"-bisnor-delta 1-THC
      7,3"-dioic acid, the major dicarboxylated urinary metabolite of delta 1-THC in
      man, is presented (preliminary results of this work have been presented in part
      at the Melbourne Symposium on Cannabis, Australia, September 1987, Ref. 1). The
      synthesis of methyl 3-(3,5-dihydroxyphenyl)-[3,3-2H2]-propanoate (8) is described
      in a nine step sequence from 3,5-dimethoxybenzoic acid in an overall yield of
      24%. Compound 8 is condensed with a terpene synthon 9 under acidic conditions,
      acetylated and hydrolyzed with red HgO and HgCl2 to afford the 1-formyl-4",5",7
      trisnor-delta 1-THC-3"-oic acid derivative (11). Compound 11 is oxidized using
      NaClO2 in 2-methyl-2-butene and hydrolyzed to give (+/-)-4",5"-bisnor-delta 1-THC
      7,3"-dioic acid (12). The same approach has been used to prepare both the
      labelled and unlabelled metabolite.

PMID- 7582965
TI  - Reactions of diazines with nucleophiles--IV. The reactivity of 5-bromo-1,3,6
      trimethyluracil with thiolate ions--substitution versus X-philic versus single
      electron transfer reactions.
AB  - Reaction of 5-Bromo-1,3,6-trimethyluracil (1) with alkylthiolate (propane-1-,
      toluene-alpha-, allyl-, etc.) ions under phase transfer catalytic conditions
      follows nucleophilic substitution and X-philic (Br and S) elimination to give 5
      alkylthio-1,3,6-trimethyluracils, 6-alkylthiomethyl-1,3-dimethyluracils and 1,3,6
      trimethyluracil. Reaction of compound 1 with heteroarylthiolate ions (pyridine-2
      , quinazoline-4-, uracil-2- and 4,6-dimethylpyrimidine-2-thiolate) gives only
      nucleophilic substitution products. However, arylthiolate (phenyl-, 4
      chlorophenyl-, 2-aminophenyl-) ions follow a single electron transfer (SET)
      mechanism to give 5-arylthio-6-arylthiomethyl-1,3-dimethyluracils along with
      normal substitution products. 1,3,6-Trimethyluracil does not react with alkyl- or
      heteroaryl-thiolate ions but reacts with arylthiolate ions (SET) providing mainly
      5-arylthio-1,3,6-trimethyluracils.

PMID- 7582964
TI  - Kinetics and mechanism of general acid-catalysed thiolytic cleavage of 9
      anilinoacridine.
AB  - The rates of the reactions of 2-mercaptoethanol (2-ME) with 9-anilinoacridine (9
      ANA) have been studied in the buffer solutions of 2-ME, hydroxylamine, phosphate
      and morpholine. Both ionised and non-ionised forms of 2-ME and free hydroxylamine
      show nucleophilic reactivity toward protonated 9-ANA. The rate constants for
      general acid-catalysed thiolytic cleavage of protonated 9-ANA reveal a Bronsted
      plot of slope (alpha) of 0.93 which indicates that probably the rate-determining
      step involves proton transfer in a thermodynamically unfavourable direction. A
      stepwise mechanism for thiolysis has been suggested. General acid catalysis could
      be detected for thiolysis of non-protonated 9-ANA only in the buffer solutions of
      phosphate and morpholine. General acid catalysis seems to be unimportant when the
      nucleophile is non-ionised 2-ME which is attributed to the probable occurrence of
      intramolecular general acid catalysis.

PMID- 7582963
TI  - Structural functions of antimicrobial long-chain alcohols and phenols.
AB  - Antimicrobial activity of a series of long-chain alcohols and common naturally
      occurring alcohols were tested against 15 selected microorganisms in order to
      gain new insights into their structural functions. The maximum activity seems to
      depend on the hydrophobic chain length from the hydrophilic hydroxyl group, and
      also the microorganisms being tested. The results obtained with the alcohols
      exhibit a generally applicable rule to many other compounds.

PMID- 7582967
TI  - Bifunctional activity labels for selection of filamentous bacteriophages
      displaying enzymes.
AB  - Two bifunctional activity labels of beta-lactamases or penicillin binding
      proteins have been prepared. They feature a penicillin sulfone derivative, i.e. a
      suicide substrate of serine beta-lactamases, or a penicillin derivative connected
      to a biotin moiety through a spacer containing a disulfide bridge. The biotinyl
      spacer 4 was prepared by coupling biotin to epsilon-amino-caproic acid, then to
      cystamine, and purified by transient protection with t-Boc. The penicillin
      sulfone inhibitor 13 was prepared by chemoselective sulfonylation of
      methoxymethyl 6-aminopenicillinate with pentafluorophenoxy- or benzyloxy
      carbonylmethylsulfonyl chloride (9), followed by permanganate oxidation. Both
      direct coupling of the activated ester 13b and indirect coupling of the acid 13c
      obtained by benzyl ester deprotection, afforded the biotinylated sulfone
      inhibitor 16. The acid 6 resulting from reaction of the biotinyl spacer 4 with
      glutaric anhydride was activated as pentafluorophenyl-ester 7 and reacted with 6
      aminopenicillanic acid to afford the penicillin binding protein label 18.
      Selection of the most active beta-lactamase displayed on phage from a mixture
      containing less active enzymes could be accomplished in three rounds of labeling
      and affinity chromatography using suicide inhibitor 16.

PMID- 7582969
TI  - Nitric oxide-induced nitration of catecholamine neurotransmitters: a key to
      neuronal degeneration?
AB  - Exposure of the neurotransmitters dopamine (1a) and norepinephrine (1b), as well
      as of other catechol compounds (1c-e), to nitric oxide (NO) in aerated phosphate
      buffer at room temperature leads to the corresponding 6-nitroderivatives (2a-e)
      in yields higher than 80%. Formation of nitration products depends on the
      presence of oxygen and is inhibited by excess ascorbic acid, whereas sulfhydryl
      compounds, e.g. cysteine, and scavengers of reactive oxygen species, such as
      catalase and superoxide dismutase, exert no significant inhibitory effect. O
      Methylated catechols are poorly or not reactive toward NO. These and other
      observations are consistent with a mechanism involving coupling of a semiquinone
      radical with NO or a higher oxide, e.g. nitrogen dioxide (NO2). The observed
      formation of potentially toxic 6-nitrocatecholamines under physiologically
      relevant conditions may open new perspectives to an understanding of the
      biochemical processes underlying NO-induced toxicity and neuronal degeneration.

PMID- 7582968
TI  - Potential radioprotective agents--VI. Chalcones, benzophenones, acid hydrazides,
      nitro amines and chloro compounds. Radioprotection of murine intestinal stem
      cells.
AB  - There is an interest and need for new compounds that protect tissues from
      radiation injury. In cancer therapy, the protection of normal tissue without
      protecting tumors is one way to increase the therapeutic gain. Thiol compounds
      are currently in clinical trials, but are limited to some extent by their human
      toxicities including hypotension, nausea, and emesis. Several new aminochalcones
      and aminobenzophenones were synthesized and tested for radioprotective activity
      in mice. All were less active than p-aminobenzophenone itself. Several acid
      hydrazides were synthesized and tested similarly, but none exhibited significant
      activity. The high radioprotective activity of 4-nitroaniline was confirmed, but
      other nitro amines were substantially less active. 4-Chloro-N-methylaniline is as
      active as 4-chloroaniline, but other chloro aromatics are devoid of significant
      activity. When compared with the phosphorothioate amyfostine (WR-2721) using the
      intestinal clonogenic cell survival assay, 1-(p-aminophenyl)-1-propanol (15), p
      aminopropiophenone (16), its ethylene ketal (14), and a mixture of the two (17)
      protected to a great extent, though slightly less than WR-2721. These results
      suggest that there is direct cellular radioprotection by these non-thiol
      compounds. The studies further suggest that preclinical toxicity testing of the
      most protective agents is warranted.

PMID- 7582971
TI  - Synthesis of mannostatins A and B from myo-inositol.
AB  - Mannostatins A and B, along with the respective enantiomer and diastereoisomer
      having the (S)-sulfinyl function, were synthesized from myo-inositol. Inhibitory
      activity of the synthetic compounds against jack bean alpha-mannosidase was
      measured, revealing that the 4-aminocyclopentane-1,2,3-triol structure plays a
      major role in interaction with the enzyme.

PMID- 7582970
TI  - N-substituted aminohydroxypyridines as potential non-opioid analgesic agents.
AB  - A series of new N-substituted aminohydroxypyridines have been synthesized,
      pharmacologically evaluated and compared with their N-substituted oxazolopyridone
      analogs. The compound with the maximal combination of safety and analgesic
      efficacy was 3-[2-[4-(4-fluorophenyl)-1-piperazinyl]ethyl]amino-2-hydroxypyridine
      (compound 10a), with ED50 values 0.4 mg kg-1 po (mouse: phenylquinone writhing
      test) and 0.5 mg kg-1 po (rat: acetic acid writhing test). Compound 10a possesses
      a potent non-opioid antinociceptive activity with moderate anti-inflammatory
      properties.

PMID- 7582972
TI  - A new strategy for the cloning, overexpression and one step purification of three
      DHAP-dependent aldolases: rhamnulose-1-phosphate aldolase, fuculose-1-phosphate
      aldolase and tagatose-1,6-diphosphate aldolase.
AB  - Three DHAP-dependent aldolases, rhamnulose-1-phosphate aldolase (Rham-1PA),
      fuculose-1-phosphate aldolase (Fuc-1PA) and tagatose-1,6-diphosphate aldolase
      (TDPA) have been cloned and overexpressed in Escherichia coli using two different
      expression vectors: pTrcHis for the expression of Rham-1PA and Fuc-1PA and pRSET
      for the expression of TDPA. In each case the recombinant enzyme is synthesized as
      a fusion protein with a hexahistidine tag on the N-terminus. The three enzymes
      have been purified in only one step by chelation affinity chromatography. The
      effects of cultivation temperature and concentration of inducer have been studied
      in order to optimize the expression of the recombinant proteins and to avoid the
      formation of inclusion bodies.

PMID- 7582973
TI  - Random mutagenesis of staphylococcal nuclease and phage display selection.
AB  - Multiple cycles of mutagenesis and phage display selection have been investigated
      as a method for obtaining enzymes with altered catalytic properties. A library of
      staphylococcal nuclease mutants displayed on phage was created by error-prone PCR
      mutagenesis and selected for binding to thymidine- or guanosine-containing
      substrate analogs. After discarding non-binders, the binding mutants were then
      subjected to further mutagenesis and selection rounds. After four mutagenesis and
      selection cycles, the catalytic properties of some of the resulting nucleases
      were studied and one nuclease with nine accumulated mutations was found to have a
      two-fold reduction in kcat for DNA hydrolysis, but a two-fold increase in kcat/Km
      for hydrolysis of a thymidine containing small molecule substrate. The
      possibility of this technique for in vitro evolution of enzyme properties is
      discussed.

PMID- 7582974
TI  - Investigation of the inhibition of leukotriene A4 hydrolase.
AB  - In an effort to better understand the favorable binding interactions between the
      reversible picomolar inhibitor 3-(4-benzyloxyphenyl)-2-(R)-amino-1- propanethiol
      (1) and leukotriene A4 (LTA4) hydrolase (EC 3.3.2.6), we prepared a number of
      derivatives of 1-L and other related structures, and assayed their inhibition of
      LTA4 hydrolase-catalyzed hydrolysis of L-alanine-p-nitroanilide. The inhibition
      data was analyzed using a weighted non-linear least-squares curve fitting
      computer program developed for this purpose to fit data derived under the non
      Michaelis-Menten condition of [I]t < [E]t. The free thiol is necessary for sub
      micromolar binding and the enzyme prefers the R enantiomer over the S enantiomer,
      in contrast to the stereoselectivity displayed towards bestatin, an inhibitor of
      somewhat similar structure. Substitution of acid moieties around the periphery of
      the benzyloxyphenyl portion of 1-L leads to substantially decreased binding,
      suggesting that this group resides within a large hydrophobic pocket when bound
      to the enzyme. Possible LTA4 binding modes in the active site of LTA4 hydrolase,
      including a possible direct role for the carboxylic acid of LTA4 in the enzyme
      catalyzed hydrolysis of leukotriene A4, are discussed.

PMID- 7582975
TI  - Crystallographic structure of a peptidyl keto acid inhibitor and human alpha
      thrombin.
AB  - The low molecular weight alpha-keto amide inhibitor CVS-1347, benzyl-SO2-Met(O2)
      Pro-Arg(CO)((CONH)CH2)-phenyl, is a slow, tight binding inhibitor of alpha
      thrombin amidolytic activity having a Ki = 1.28 x 10(-10) M. A complex between
      human alpha-thrombin and a hydrolysis product of CVS-1347 has been determined and
      refined using crystallography. The crystals belong to monoclinic space group C2
      with cell dimensions of a = 71.08, b = 72.05 and c = 72.98 A and beta = 100.8
      degrees. The structure was solved using isomorphous replacement methods and
      refined with resolution limits of (8.00-1.76) A to an R-value of 0.162. The Pro
      Arg core of the inhibitor binds in the S2 and S1 subsites respectively, as is
      usually observed for Pro-Arg thrombin inhibitors. The Met(O2) side chain does not
      make any close contacts with the enzyme but influences the conformation of
      Glu192; the N-terminal benzylsulfonyl group makes an aromatic-aromatic contact
      with Trp215 in the hydrophobic part of the active site. The alpha-keto carboxylic
      acid of the proteolyzed inhibitor binds with the carboxylate group in the
      oxyanion hole, demonstrating that this region can accommodate an anion in a
      protease-peptide complex. The alpha-keto carbonyl group interacts closely with
      the two most important residues in the active site: the carbon atom is within a
      covalent bond distance of the active site Ser195 O gamma and the carbonyl oxygen
      is hydrogen bonded to His57.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582976
TI  - New tripeptidic thrombin inhibitors. Influence of P2 and P3 residues on activity
      and selectivity.
AB  - Structural variations of P2 and P3 residues in tripeptidic boroarginine thrombin
      inhibitors led to compounds with similar potency than reference compound DuP 714,
      but with enhanced selectivity for thrombin compared to plasmin.

PMID- 7582977
TI  - Cyclotheonamide derivatives: synthesis and thrombin inhibition. Exploration of
      specific structure-function issues.
AB  - Macrocyclic pentapeptide analogues (5-9) of the sponge natural product
      cyclotheonamide A (CtA, 3) were prepared by means of our convergent [3 + 2]
      synthetic protocol, in which a late-stage primary amine group is available for
      substitution (Maryanoff et al. Proc. Natl Acad. Sci. U.S.A. 1993, 90, 8048).
      These analogues, as well as CtA and cyclotheonamide B (CtB, 4), were examined for
      their ability to inhibit the serine protease alpha-thrombin, in comparison with
      suitable reference standards. We characterized Michaelis-Menten and slow-binding
      kinetics for the cyclotheonamide derivatives. An attempt was made to utilize the
      unoccupied hydrophobic S3 subsite of thrombin via analogues 5 and 6. Also,
      removal of the hydroxyphenyl group, which is thought to be involved in an
      aromatic stacking interaction with Trp60D of thrombin, was explored via analogue
      9. The importance of the alpha-keto and olefin groups was examined via 7 and 8,
      respectively. The relationship of structure and function with the analogues
      proved to be less predictable than anticipated.

PMID- 7582978
TI  - Molecular modeling studies of novel retro-binding tripeptide active-site
      inhibitors of thrombin.
AB  - A novel series of retro-binding tripeptide thrombin active-site inhibitors was
      recently developed (Iwanowicz, E. I. et al. J. Med. Chem. 1994, 37, 2111(1)). It
      was hypothesized that the binding mode for these inhibitors is similar to that of
      the first three N-terminal residues of hirudin. This binding hypothesis was
      subsequently verified when the crystal structure of a member of this series, BMS
      183,507 (N-[N-[N-[4-(Aminoiminomethyl)amino[-1-oxobutyl]-L- phenylalanyl]-L-allo
      threonyl]-L-phenylalanine, methyl ester), was determined (Taberno, L.J. Mol.
      Biol. 1995, 246, 14). The methodology for developing the binding models of these
      inhibitors, the structure-activity relationships (SAR) and modeling studies that
      led to the elucidation of the proposed binding mode is described. The crystal
      structure of BMS-183,507/human alpha-thrombin is compared with the crystal
      structure of hirudin/human alpha-thrombin (Rydel, T.J. et al. Science 1990,
      249,227; Rydel, T.J. et al. J. Mol Biol. 1991, 221, 583; Grutter, M.G. et al.
      EMBO J. 1990, 9, 2361) and with the computational binding model of BMS-183,507.

PMID- 7582980
TI  - Amide and alpha-keto carbonyl inhibitors of thrombin based on arginine and
      lysine: synthesis, stability and biological characterization.
AB  - We report structure-activity investigations in a series of tripeptide amide
      inhibitors of thrombin, and the development of a series of highly potent active
      site directed alpha-keto carbonyl inhibitors having the side chain of lysine at
      P1. Compounds of this class are unstable by virtue of reactivity at the
      electrophilic carbonyl and racemization at the adjacent carbon (CH).
      Modifications of prototype alpha-keto-ester 8a have afforded analogs retaining
      nanomolar Ki. Optimal potency and stability have been realized in alpha-keto
      amides 11b (Ki = 2.8 nM) and 11c (Ki = 0.25 nM).

PMID- 7582981
TI  - Active site-directed thrombin inhibitors: alpha-hydroxyacyl-prolyl-arginals. New
      orally active stable analogs of D-Phe-Pro-Arg-H.
AB  - D-alpha-Hydroxyacyl-prolyl-arginals have been designed and synthesized as orally
      active stable analogs of D-Phe-Pro-Arg-H, the active site-directed peptidyl
      thrombin inhibitor prototype. Many of the new analogs possess high in vitro
      anticoagulant activity while having little effect on fibrinolysis. Compounds GYKI
      66104 (2), -66131 (3) and -66132 (5) effectively delay the clotting time in
      rabbits ex vivo and prevent thrombus formation in various thrombosis models in
      rabbits and rats when applied in a single oral dose of 5 mg kg-1.

PMID- 7582982
TI  - Rates of thrombin acylation and deacylation upon reaction with low molecular
      weight acylating agents, carbamylating agents and carbonylating agents.
AB  - Acylated derivatives of thrombin have been made using low molecular weight
      acylating agents, carbamylating agents and carbonylating agents. The compounds
      used to acylate the active site serine include isatoic anhydrides,
      benzoxazinones, benzylisocyanate, N-(benzylcarbonyloxy)succinimide and p
      (dimethylamino)benzoylimidazolide. The rates of acylation and deacylation were
      determined. The best overall inhibitors of thrombin are 2-ethoxy-4H-3,1
      benzoxazin-4-one, isatoic anhydride and tert-butyl-2,4-dioxo-2H-3,1-benzoxazine
      1(4H)-acetate, which have k2/Ki values of 52,700 M-1s-1, 48,900 M-1s-1 and 5400 M
      1s-1, respectively. The carbamyl derivative of thrombin formed with
      benzylisocyanate had the slowest rate of deacylation (2.3 x 10(-7) s-1), while
      the ester derivative formed with 2-(N,N-dimethylamino)methylimino-4H-3,1
      benzoxazin-4-one had the fastest rate of deacylation (1.9 x 10(-4) s-1).

PMID- 7582979
TI  - Synthesis and comparison of tripeptidylfluoroalkane thrombin inhibitors.
AB  - Fluorinated ketone thrombin inhibitors based on the peptide sequence methyl-(D)
      Phe-Pro-Arg-CF2R were synthesized: MDL 73,446 (1, R = F); MDL 73,775 (2, R =
      CF3); and MDL 75,579 (3, R = CH2CH2CH3). These were shown to be highly effective,
      slow binding inhibitors of thrombin. Anticoagulant activity was dose-dependent
      with 3 > 2 > 1 at doubling thrombin time and APTT, respectively. Anticoagulant
      activity corresponded with efficacy in a platelet-dependent (FeCl3-induced) rat
      carotid artery thrombosis model. Arterial occlusion was dose-dependently
      prolonged with 3 > 2 > 1 at doubling the occlusion time.

PMID- 7582983
TI  - Peptide-derived transition state analogue inhibitors of thrombin; synthesis,
      activity and selectivity.
AB  - In a study to combine the transition state analogue concept with the principle of
      catalytic site spanning, a series of peptide-derived transition state analogue
      (TSA) inhibitors of thrombin has been synthesized and tested. In the sequence H-D
      Phe-Pro-Arg-Gly-OH (2) the Arg-Gly amide bond has been replaced by three classes
      of transition state analogues, being the ketomethylene, the hydroxyethylene and
      the hydroxymethylene amide bond replacements. Compound 12a, in which the amide
      bond has been replaced by the ketomethylene group, was found to be the most
      potent thrombin inhibitor of the series studied. Subsequently, penta- and
      hexapeptide sequences with good affinity for thrombin were developed, i.e. H-D
      Phe-Pro-Arg-Gly-Phe-OH (16) and H-D-Phe-Pro-Arg-Gly-Phe-Lys-OH (26). In these
      sequences the Arg-Gly amide bond was then replaced by the ketomethylene group.
      The resulting compounds 43a and 47a, respectively, were evaluated in vitro as
      inhibitors of thrombin and factor Xa. Compound 47a was found to be the most
      potent thrombin inhibitor of the series studied (Ki = 29 nM). The combination of
      the transition state analogue concept and the principle of peptide elongation
      (tetrapeptide-->hexapeptide) yields thrombin inhibitors of high potency and
      selectivity. The effects of these two alterations reinforce each other indicating
      a synergistic effect. This might be rationalized by entropy factors.

PMID- 7582984
TI  - Three more cyclotheonamides, C, D, and E, potent thrombin inhibitors from the
      marine sponge Theonella swinhoei.
AB  - Three new thrombin and trypsin inhibitors, cyclotheonamides C (3), D (4), and E
      (8) were isolated from the marine sponge Theonella swinhoei. Their structures
      were determined by spectral and chemical methods.

PMID- 7582985
TI  - Azetidin-2-one derivatives as inhibitors of thrombin.
AB  - A series of 3-(3-guanidinopropyl)-azetidin-2-one derivatives was prepared and
      evaluated as inhibitors of cleavage of synthetic substrates in vitro by the
      serine proteases thrombin, trypsin and plasmin. The N-unsubstituted, 4-phenethyl
      derivative 9a demonstrated weak inhibition of these enzymes but acetylation of
      the beta-lactam N atom afforded 9b, an effective, time-dependent inhibitor of
      thrombin and a potent inhibitor of plasmin. Variation of the 4-position of the
      beta-lactam ring was examined in conjunction with different N-substituents to
      provide a series of potent, time-dependent inhibitors of thrombin. A C-4
      substituent was essential for good inhibitory properties and, in general, polar C
      4 substituents enhanced the selectivity of inhibition for thrombin compared to
      plasmin. A trans relationship between the C-4 and C-3 substituents was found to
      be superior to a cis disposition whilst homologation of the guanidinopropyl side
      chain to that of a guanidinobutyl moiety reduced activity. Several compounds were
      effective inhibitors of thrombin-induced clot formation in human plasma in vitro
      but activity in this assay did not correlate well with inhibition of thrombin
      induced cleavage of a synthetic substrate, presumably a consequence of inherent
      chemical instability and degradation in plasma.

PMID- 7582988
TI  - Peripheral thrombolysis: state of the art.
AB  - Peripheral thrombolysis has become established in the last decade as an
      alternative method of treatment for acute limb ischaemia. New techniques of
      accelerated thrombolysis have expanded the indications to include almost all
      affected patients. Attention to detail and avoidance of known pitfalls, together
      with close cooperation between vascular surgeon and radiologist, ensure optimum
      results with minimum complications. A modern integrated lysis programme may vary
      from initial thrombolytic treatment for all patients with acute limb ischaemia to
      a selective policy of surgery and thrombolysis depending on the aetiology and
      severity of ischemia.

PMID- 7582989
TI  - Does an aortopulmonary shunt before repair of tetralogy of Fallot limit exercise
      tolerance in long-term survivors?
AB  - The purpose of this study was to evaluate the impact of an aortopulmonary shunt
      on exercise capacity in long-term survivors after total repair of tetralogy of
      Fallot (17.6(2.0) years' follow-up). Submaximal exercise tests, pulmonary
      function tests, lund diffusion tests for carbon monoxide, two-dimensional and
      Doppler echocardiography were performed in 12 patients with an aortopulmonary
      shunt (group A) and in 21 patients (group B) without a shunt before repair. There
      were no significant differences in two-dimensional and Doppler echocardiographic
      findings nor in pulmonary function. Group A showed a significantly lower
      diffusion capacity of the lung for carbon monoxide at rest (66.2(13.0)% versus
      84.1(9.5)%; P < 0.01) and at the anaerobic threshold (71.8(11.0)% versus
      87.2(9.8)%; P < 0.01) as well as a significantly reduced physical working
      capacity at ventilatory anaerobic threshold (1.6)(0.32) W/kg versus 2.41(0.43)
      W/kg; P < 0.01). A negative correlation was observed between the duration of
      palliative shunts and diffusion capacity of the lung for carbon monoxide at rest
      at ventilatory anaerobic threshold (r = -0.8635 and -0.9108 respectively). A
      shunt placed before definitive repair impairs the long-term working capacity,
      probably by diminishing the diffusion capacity of the lung for carbon monoxide,
      especially if the shunt is in place for more than 20 months.

PMID- 7582990
TI  - Flow study of surgical coronary artery fistula as an alternative to sequential
      bypass.
AB  - Surgical coronary artery fistula, in which the last anastomosis is created to a
      low-pressure cardiac chamber, was recently introduced as an alternative method to
      improve graft flow and patency in a sequential graft when coronary arteries are
      small or diffusely diseased. To assess graft flow, effect on haemodynamics, flow
      distribution and to determine proper size of the distal anastomosis, a saphenous
      vein was sequentially anastomosed from the ascending aorta to the left anterior
      descending artery and then to the left atrium in eight mongrel dogs. Graft flow
      was measured before and after opening the fistula to the left atrium between the
      ascending aorta and left anterior descending artery (flow A) and between the left
      anterior descending artery and left atrium (flow B). Left atrium pressure and
      systolic left ventricular pressure (mmHg) were recorded. The diameter of the
      distal anastomosis was regulated with a bulldog clamp. When distal anastomosis
      was at 2.5-3 mm mean(s.d.) flow A increased from 64.5(19.5) to 134.7(28.5) ml/min
      (P < 0.01) without significant left atrial pressure or left ventricular pressure
      change. With a distal anastomosis of 4 mm or more, flow A increased from
      69.8(19.9) to 396.1(62.2) ml/min (P < 0.001). Left atrial pressure increased from
      5.6(1.0) to 6.1(0.9) mmHg (P < 0.05) without a change in left ventricular
      pressure. In both sizes of distal anastomosis, flow to the left anterior
      descending artery did not change either before or after the shunt (flow B) was
      opened. Neither volume loading, rapid atrial pacing, neosynephrine or epinephrine
      infusions caused deleterious haemodynamic effects with the shunt open.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7582987
TI  - Thrombin active site inhibitors.
AB  - Development of small molecule thrombin active site inhibitors has been an area of
      intense research. A brief review on recent progress and challenges is outlined.

PMID- 7582986
TI  - Active site-directed thrombin inhibitors--II. Studies related to
      arginine/guanidine bioisosteres.
AB  - A series of N-arylsulfonylarginine amides was synthesized wherein the guanidine
      or arginine moiety was isosterically replaced by a number of heterocyclic
      functionalities. These compounds were evaluated as potential active-site
      inhibitors of thrombin. Bisamidines 11a-n showed a similar SAR to that of simple
      arginine compounds. The ex vivo clotting time measurement of 11d after ip dosing
      showed prolongation of clotting time in rats.

PMID- 7582994
TI  - Ischemia-reperfusion injury of the spinal cord: the influence of normovolemic
      hemodilution and gradual reperfusion.
AB  - Recent studies have suggested that oxygen-derived free radicals play an important
      role in ischemia-reperfusion injury of the spinal cord. In other organ systems,
      reperfusion injury has been reduced by limiting the availability of oxygen in the
      reperfusion phase. The purpose of this study was to test the effect of
      normovolemic hemodilution and gradual reperfusion on spinal cord function after
      aortic cross-clamping in 84 New Zealand White rabbits. All animals underwent 21
      min of infrarenal aortic cross-clamping in the conscious state by means of a
      previously placed aortic occlusion device and were randomized to four groups.
      Group 1 animals were hemodiluted to a mean (s.e.m.) hematocrit of 28(2)% by
      extracting 25% of the effective blood volume and reinfusing the plasma component
      after centrifugation concurrently with a volume of normal saline three times that
      of the discarded red cells. Group 2 animals (controls) were bled similarly but
      both plasma and red cells were reinfused, resulting in a mean (s.e.m.) hematocrit
      of 38(2)%. In the next two groups, distal aortic flow was recorded via an
      implantable Doppler device. After cross-clamping, flow was returned gradually
      over 45 min in animals of group 3, and abruptly in group 4. Animals were observed
      for 5 days and neurologic function was graded by an independent observer.
      Paraplegia at 5 h after clamping occurred in 75% of animals in group 1 versus 32%
      in group 2 (P < 0.05), and in 33% of group 3 versus 28% in group 4 (not
      significant). Of those animals showing initial neurologic recovery, delayed-onset
      paraplegia was seen in 100% in group 1 versus 87% in group 4 (not significant),
      and in 50% of group 3 versus 92% of group 4 (P < 0.03).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7582992
TI  - Long-term results of mitral valve repair for non-rheumatic mitral regurgitation.
AB  - The durability of mitral valve repaired with reconstructive techniques is
      variable. If the durability continues to be good, mitral valve repair may be the
      procedure of choice in many patients with mitral regurgitation. Between December
      1970 and June 1993, 54 patients had mitral valve repair for non-rheumatic mitral
      regurgitation. There were 38 men and 16 women with a mean age of 46.8 (range 19
      68) years. The pathology which required surgical treatment was torn chordae in 38
      patients, elongation of the chordae in five, valve prolapse without elongation or
      rupture of the chordae in six, infective endocarditis in three, and annular
      dilatation in two. Forty-four patients had triangular or quadrangular resection
      of the mitral leaflet, and seven had annuloplasty alone. Choral reconstruction
      was performed on three patients. There were no operative deaths. Five patients
      (9%) died late after operation. The actuarial survival rate and the valve-related
      death-free rate at 10 years were 83.9% and 90.0%, respectively. Seven patients
      (13%) required reoperation. Freedom from reoperation at 10 years was 84.5%.
      Improper evaluation of residual regurgitation during operation and suture
      dehiscence were the principal causes of reoperation. It was concluded that mitral
      valve repair for non-rheumatic mitral regurgitation showed low operative
      mortality and stable long-term results. It is suggested that intraoperative
      transoesophageal colour Doppler echocardiography provides accurate assessment of
      mitral valve competence and may be helpful in reducing the need for reoperation.

PMID- 7582991
TI  - Pressure characteristics in arterial grafts for coronary bypass surgery.
AB  - The haemodynamic properties of arterial grafts were studied by measuring the
      pressure waveform at the tip of the grafts in 28 patients who underwent coronary
      artery bypass surgery (CABG). The internal thoracic and gastroepiploic arteries
      were harvested as pedicles for CABG. Pressure wave of the ascending aorta and
      arterial grafts were simultaneously recorded with an electrocardiogram under
      stable haemodynamic conditions before cardiopulmonary bypass. Systolic, diastolic
      and mean pressures were measured, and mean systolic and diastolic pressures
      calculated for systolic and diastolic areas divided by time. The ascending aorta
      showed high sustained diastolic pressure that decreased gradually. Pressures in
      the internal thoracic and gastroepiploic artery grafts had narrow contours and
      decreased rapidly. Pressure waveforms in the internal thoracic and gastroepiploic
      artery grafts had a notch between the systolic and diastolic contours. There was
      no difference in systolic pressure between the ascending aorta and internal
      thoracic and gastroepiploic artery grafts. Diastolic pressures were 64(9), 55(7),
      and 51(6) mmHg in the ascending aorta and internal thoracic and gastroepiploic
      artery, respectively. Mean(s.d.) pressures were 75(9), 65(9) and 59(7) mmHg in
      the ascending aorta and internal thoracic and gastroepiploic artery grafts,
      respectively. Diastolic and mean pressures in the internal thoracic artery grafts
      were significantly lower than in the ascending aorta but significantly higher
      than in the gastroepiploic artery grafts. The mean(s.d.) calculated diastolic
      pressure in the internal thoracic artery grafts was significantly lower than in
      the ascending aorta but significantly higher than in the gastroepiploic artery
      grafts. The inferior capacity of flow through the arterial grafts may be mainly
      attributable to reduced diastolic pressure, which is caused by anatomical
      characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582993
TI  - Combined internal cardioverter-defibrillator implantation and myocardial
      revascularization for ischemic ventricular arrhythmias: optimal cost-effective
      strategy.
AB  - During the 7-year period from August 1986 to July 1993, 203 patients with
      malignant ventricular arrhythmias underwent 203 implantable cardioverter
      defibrillator (ICD system) implantations at the University Hospitals of
      Cleveland. Sixty-four patients had significant coronary artery stenoses amenable
      to myocardial revascularization and thus, at the time of the operation for ICD
      placement, also underwent coronary artery bypass graft. A retrospective analysis
      of the course of these 64 patients was carried out to determine the effect of two
      different treatment strategies on the outcome and cost of therapy. Thirty-six
      patients (group 1) underwent concomitant implantation of the ICD leads, patches
      and generator at the time of myocardial revascularization; 28 patients (group 2)
      underwent a two-stage strategy of initial placement of the ICD leads and patches
      at the time of myocardial revascularization followed by postoperative
      electrophysiologic testing to determine the persistent need for generator
      implantation. Of this latter group, 16 patients still had inducible sustained
      ventricular tachycardia during postoperative electrophysiologic testing and
      underwent generator implantation; 12 patients did not receive an ICD generator.
      The overall 30-day mortality rate was 4.7%. Two patients died in group 1 for a
      mortality rate of 5.5% and one died in group 2 for a mortality rate of 3.6%. The
      mean(s.d.) length of stay was 22.8(9.6) days at a mean(s.d.) cost of
      $93,000(33,000) for group 1 and 24.5(9.6) days at a mean cost of $82,900(30,000)
      for group 2 (P = n.s.). The mean(s.d.) postoperative length of stay was 13.7(7.8)
      days for group 1 and 15.4(6.5) days for group 2 (P = n.s.). Other complications
      occurred in 23% of surviving patients in group 1 and 29% of surviving patients in
      group 2 (P = n.s.). Mean follow-up was 33 months for group 1 and 23 months for
      group 2. At the end of 2 years, 78% of patients in group 1 and 86% in group 2
      were alive (P = n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7582995
TI  - Beneficial effects of prostacyclin treatment on reperfusion of the myocardium.
AB  - A total of 20 patients with coronary artery disease were studied in order to
      assess the benefits of prostacyclin administration on reperfusion of the
      ischaemic myocardium after cardiopulmonary bypass. Ten received prostacyclin (25
      ng/kg per min) while ten were untreated controls. There was no difference between
      groups with regard to age, preoperative ejection fraction and aortic cross
      clamping times. There were no in-hospital deaths in either group. The
      administration of prostacyclin significantly altered the metabolic side effects
      of reperfusion followed by hypothermic cardioplegic arrest. Myocardial oxygen
      consumption after cardiopulmonary bypass was significantly higher in the
      prostacyclin-treated group than in controls (18.5 ml versus 13 ml; P < 0.01).
      Prostacyclin treatment significantly reduced the leucocyte activity: leukotriene
      B4 concentrations were 58 pmol/l in prostacyclin-treated patients compared with
      93 pmol/l in controls (P < 0.01). Such recovery of metabolic status during
      reperfusion resulted in better haemodynamic function in patients receiving
      prostacyclin.

PMID- 7582996
TI  - Vascular emergencies: what's in season?
AB  - Seasonality in ischaemic coronary artery disease is well documented with a
      winter/summer variation the commonest pattern. The influence of seasonal
      variation on events in other vascular territories is less well documented. The
      incidence of ruptured abdominal aortic aneurysm and emergency lower-limb
      ischaemia was analysed on a monthly basis over a 5-year period. A total of 372
      ruptured abdominal aortic aneurysms occurred with a peak incidence in spring and
      autumn; however, no seasonal pattern was seen in the rate of emergency admissions
      with lower-limb ischaemia (n = 606). The explanation for this seasonal pattern in
      ruptured aneurysms is unknown. The haemodynamic adjustments to changes in climate
      require further study.

PMID- 7582997
TI  - Renal artery anomalies in patients with horseshoe or ectopic kidneys: the
      challenge of aortic reconstruction.
AB  - Renal fusion or ectopia can present formidable challenges during aortic surgery.
      To evaluate morbidity and define optimal management, the clinical histories of 20
      patients with renal fusion or ectopia who underwent 21 aortic procedures at the
      authors' institution over a 37-year period were reviewed. Indications for surgery
      included aortic aneurysm in 16 patients (infrarenal in 15 and thoracoabdominal in
      one) and aortoiliac occlusive disease in five (with renovascular hypertension in
      two). The abnormal kidney was detected before surgery in 13 patients (65%) by
      excretory urography, arteriography, computed tomography, or ultrasonography.
      Arteriography revealed multiple and/or anomalous renal arteries in nine of 12
      patients studied. At surgery, 15 patients (75%) were found to have multiple or
      anomalous renal arteries. Six required renal revascularization (reimplantation
      four, endarterectomy one, aortorenal bypass one). The renal symphysis was divided
      in two patients. There were no operative deaths. Six major complications included
      bleeding requiring reoperation, renal failure requiring short-term dialysis,
      pancreatitis, gastrointestinal bleeding, pneumonia and thrombophlebitis.
      Preoperative aortography is recommended in patients with renal fusion or ectopia
      because of the high incidence of associated renal artery anomalies. The surgeon
      must be prepared to preserve or revascularize these anomalous renal arteries.
      Division of the renal symphysis is rarely required. Although perioperative
      morbidity is raised, aortic reconstruction in patients with renal fusion or
      ectopia can be safely performed without increased mortality.

PMID- 7582998
TI  - Does concomitant aortic bypass and renal artery revascularization using the
      retroperitoneal approach increase perioperative risk?
AB  - While elective repair of abdominal aortic aneurysms and aortoiliac occlusive
      disease is associated with an acceptable (3%) mortality rate, combined aortic and
      renal revascularization has usually been reported to have a higher perioperative
      mortality. Over the past 5 years, 785 elective aortic procedures have been
      performed at the authors' medical center. During the same period, 77 renal artery
      reconstructions have been performed in 73 patients in conjunction with aortic
      procedures. All were done using the retroperitoneal approach to the aorta and
      renal arteries. Indication for concomitant renal artery revascularization
      included 79% (61 of 77 patients) for either significant stenosis or anatomic
      involvement, 18% for renovascular hypertension (14 of 73) and 3% (two of 73) for
      renal impairment. The demographics and risk factors were similar in both groups.
      Operative mortality rate was 2.9% (23 of 785) in the aortic group and 3% (two of
      73) in the combined group. Complications in the combined group were one stroke
      (1.4%), one re-exploration for bleeding (1.4%), two pulmonary pneumonia (2.7%)
      and five patients had elevated serum creatinine (> 350 mumol/l) after operation.
      Of these patients two died, one had an occluded graft and two eventually
      improved. There was one early graft thrombosis and one late thrombosis. In the
      authors' experience, concomitant aortic bypass and renal artery revascularization
      can be performed with an acceptable mortality and morbidity using the
      retroperitoneal approach.

PMID- 7582999
TI  - Autogenous venous bypass grafts and limb salvage: 5-year results in 1971 and
      1991.
AB  - Claims have been made that the increased utilization of arterial reconstruction
      has not resulted in improved limb salvage. This report compares the results of
      two series of patients with autogenous venous bypass grafts and examines the
      institutional trends at a major regional vascular center with these procedures.
      The two groups of patients underwent operation between 1957 and 1964 (group I)
      and 1982 and 1985 (group II) respectively. Each patient was followed for a
      minimum of 5 years or until death. This review showed that the demographics of
      the population and the nature of the operation changed dramatically over the 20
      year period. Patients were older, had more medical co-morbid conditions, more
      operations were performed for salvage and more to vessels below the knee joint in
      the latter series. Despite these adverse factors, the 30-day patency rates were
      significantly better in the later group, 93% versus 76%. Likewise, limb salvage
      rates were improved both initially and after the 5-year period of observation.
      The 5-year primary patency, however, was no different between groups I and II,
      60% versus 56%. Since both series preceded the use of duplex scanning for graft
      surveillance, even further improvements in both graft patency and limb salvage
      rates would be expected in patients currently treated.

PMID- 7583003
TI  - Venous aneurysm of extremities: a case report and literature review.
AB  - A case of venous aneurysm of the short saphenous vein is described in a young
      woman. The aetiology, diagnosis and treatment of this rare anomaly is reviewed.

PMID- 7583000
TI  - Improvement in suction catheter efficiency and safety in arterial operations.
AB  - The Blood Shield is a new device which has been developed to attach easily to the
      tip of a conventional suction catheter. Two experiments were performed to
      determine if the Blood Shield could limit the degree of splash which occurs
      during vascular graft flushing and whether it could increase the efficiency of a
      standard suction tip in collecting shed blood for autotransfusion. The results of
      the experiments indicate that the Blood Shield, when added to a conventional
      suction catheter, diminishes the amount of spray which may occur during
      anastomotic flushing. Secondly, it more effectively collects blood from a flushed
      anastomosis or arteriotomy in comparison with a suction catheter alone.

PMID- 7583001
TI  - Tensile strength and histological changes of abdominal aorta of malnourished
      rats.
AB  - The resistance of the abdominal aorta of rats after 6, 7 and 8 weeks of
      malnutrition, compared with control animals, was evaluated by longitudinal
      tensiometry. Weakness of this vessel in malnourished rats was demonstrated;
      microscopic examination of the aorta stained by Masson, Calleja and hematoxylin
      eosin methods showed a decrease in amorphous ground substance and an increase in
      the width of elastic laminae. There was no visible alteration either in the
      endothelial lining layer or in the smooth muscle fibers. Such alterations of the
      aorta are, to the authors' knowledge, the first reported modifications in the
      peripheral vasculature after malnutrition.

PMID- 7583002
TI  - Recurrent aortic infection: treatment by arterial homograft replacement.
AB  - Deep infection remains the most problematic complication following prosthetic
      aortoiliofemoral reconstruction. Prosthetic excision and extra-anatomic
      revascularization is associated with significant morbidity and mortality. The
      possibilities of autogenous reconstruction are frequently limited. The authors
      present a patient with recurrent aortic infection who was successfully treated by
      prosthetic excision and revascularization in situ with a cryopreserved arterial
      homograft.

PMID- 7583004
TI  - Gradient of integrin alpha 6A distribution in the myocardium during early heart
      development.
AB  - The interactions of cells with extracellular matrices (ECM)1 are likely to be key
      determinants of embryonic development. Integrin adhesion receptors are ideally
      positioned to mediate some of these interactions since, in addition to mechanical
      adhesion, they transduce signals affecting cell proliferation and
      differentiation. We investigated expression of the integrin alpha 6 beta 1, a
      receptor for the ECM component, laminin in the early mouse embryo. An intriguing
      feature of this integrin is the existence of alpha 6 subunit isoforms. The A and
      B isoforms, which differ in the cytoplasmic tails, are expressed in cell-type
      specific fashion, and are likely to implement distinct cellular interactions with
      laminin. By RT-PCR, alpha 6B but not alpha 6A mRNA was detectable in embryo
      extracts from fertilized oocytes to 6.5 d.p.c. In subsequent stages, up to 11.5
      d.p.c., alpha 6A mRNA was observed in mRNA extracts from whole embryos, but still
      in significantly lower amounts than alpha 6B. However, in extracts from isolated
      heart (9.5 to 11.5 d.p.c.), alpha 6A was the predominant alpha 6 isoform, while
      in extracts from other embryo parts no alpha 6A mRNA was detectable. At the
      protein level, immunostaining with specific antibodies showed alpha 6A protein in
      myocardial cells, at the early stage of heart tube development (8.5 d.p.c.).
      Localization to the myocardium was tightly restricted, since other structures of
      the embryonic heart, e.g., endocardium, or of the remaining embryo did not stain
      with anti-alpha 6A antibody. In the ventricular myocardium, expression of alpha
      6A appeared more intense than in the subendocardial layer. Quantitation by
      confocal microscopy unveiled a gradient of expression of alpha 6A, increasing
      from the outer to the inner layers of the myocardium. This is the first
      demonstration of a gradient distribution of integrin molecules in a tissue, which
      appears to be directly connected with the process of organogenesis. The mechanism
      underlying our observations is not the turning on of a gene, rather it is the
      activation of a splicing mechanism that substitutes the cytoplasmic domain of a
      laminin receptor. Because integrin cytoplasmic domains are thought to be an
      important functional end of the molecule, this may be a mechanism to modulate
      cellular responses to laminin.

PMID- 7583005
TI  - Cadherin 11 expression marks the mesenchymal phenotype: towards new functions for
      cadherins?
AB  - Cadherin-11 (cad-11) belongs to the cell adhesion type II cadherin family, which
      seems to have different functions from the classic cadherin family. This study
      shows the overall pattern of cad-11 gene expression during rat embryonic
      development, from the pregastrula to very late embryonic stage. Cad-11 is the
      first cadherin found to be highly expressed in the dispersed and migrating
      mesenchymal cells that originate from the neuroectodermal neural crest cells and
      from the pre-chordal and paraxial mesoderm. A burst of cad-11 expression appears
      during the epithelial to mesenchymal transition, as observed by sclerotome
      formation. Cad-11 mRNAs were present in all mesenchymal cells throughout the
      embryo, regardless of their embryonic origin. A proximo-distal and antero
      posterior gradient of cad-11 expression is seen in the limb buds, genitalia, and
      tail. As development proceeds, while all epithelium are negative, cad-11 is
      present in all mesenchymal cells involved in various morphogenetic events, such
      as the mesenchyme condensations during chondrogenesis and in the formation of
      sclera, cornea, naris, palate and meninges. Cad-11 was strongly expressed in
      mesenchyme during lung or kidney branching morphogenesis or the many epithelium
      to mesenchyme inductions that operate in the nasal septum, skin, vibrissae, teeth
      and various glands. High levels of cad-11 transcripts were also found in the
      dispersed cells of the hyaloid plexus in the vitreous body and in the invading
      mesenchyme within the trabeculae of the outflow tract of the heart. Cad-11 is
      thus specific to the mesenchymal phenotype whatever the stage of embryonic
      development.

PMID- 7583006
TI  - Vascular cell adhesion molecule (VCAM)-Ig fusion protein defines distinct
      affinity states of the very late antigen-4 (VLA-4) receptor.
AB  - The Very Late Antigen-4 receptor (VLA-4) (alpha 4 beta 1) is constitutively
      expressed on leukocytes and plays a role in cell trafficking, activation and
      development through its interaction with two alternative ligands, Vascular Cell
      Adhesion Molecule (VCAM-1) and fibronectin (FN). VLA-4-dependent cell adhesion is
      augmented by various stimuli, such as divalent cations, certain beta 1-specific
      monoclonal antibodies (mAbs) and cell activation. However, the steps of the
      adhesive process which they affect are currently undefined. In order to
      investigate whether or not these stimuli affect the primary step, VLA-4/ligand
      binding, we employed a recombinant VCAM-IgG fusion protein (VCAM-Ig) as a soluble
      ligand for VLA-4. Using this soluble ligand, we have directly demonstrated that
      the VLA-4 receptor can exist in at least three different affinity states on the
      cell surface. Two distinct high affinity states are induced on normal peripheral
      blood T cells, one by the anti-beta 1 mAb TS2/16, and one of 15-20 fold higher
      affinity by the divalent cation Mn2+. Interestingly, activation through the T
      cell receptor (TcR), through CD31 or by the Macrophage Inflammatory Protein-1
      beta chemokine (MIP-1 beta) do not detectably increase VLA-4 affinity although
      they do augment VLA-4 dependent cell adhesion in vitro. Thus, VCAM-Ig binding
      defines high affinity VLA-4 receptors, revealing unique effects of the TS2/16 mAb
      and Mn2+ cations in vitro, and distinguishes VLA-4/VCAM interactions from
      subsequent steps in cell adhesion.

PMID- 7583007
TI  - An alternatively spliced exon in the extracellular domain of the human alpha 6
      integrin subunit--functional analysis of the alpha 6 integrin variants.
AB  - Variants in the extracellular domain of the integrin alpha 7 subunit which arise
      as a consequence of alternative splicing of mRNA have recently been reported. Two
      alternative exons, X1 and X2, have been identified in the alpha 7 gene, and
      homologous exons were found for alpha 6 (Ziober et al., 1993). In this study, we
      have isolated the region of the alpha 6 gene containing exons X1 and X2 that are,
      like those of alpha 7, located between stretches of DNA that encode the
      homologous repeat domains III and IV, proximal to the three divalent cation
      binding sites of the alpha 6 subunit. We demonstrated by reverse transcriptase
      polymerase chain reactions and confirmed by sequencing that alpha 6X1 and alpha
      6X1X2 mRNAs are generated by alternative splicing of exon X2. The alpha 6X1X2
      mRNA is expressed in a limited number of tissues and cell lines and it is always
      co-expressed with the ubiquitous alpha 6X1 mRNA. Stable transfection of K562
      cells with full length cDNAs for the alpha 6AX1X2 and beta 4 subunits resulted in
      cell populations that expressed the alpha 6AX1X2 variant, in association with
      either beta 1 or beta 4, on their surface. In addition, a population of cells was
      isolated that expressed the alpha 6AX1X2 variant at low levels and almost
      exclusively in association with beta 1. Comparison of the alpha 6AX1X2 integrins
      with alpha 6AX1 using similarly transfected cells showed no obvious differences
      between the alternative extracellular alpha 6A isoforms with respect to ligand
      specificity and activation-dependency of ligand binding. After treatment with the
      anti-beta 1 stimulatory antibody TS2/16, both the alpha 6AX1 beta 1 and alpha
      6AX1X2 beta 1 integrin variants mediated cell adhesion to EHS tumor laminin
      (laminin-1), kalinin (laminin-5), human placental (laminin-2 and -4) and bovine
      kidney laminins. In contrast, the alpha 6AX1 beta 4 and alpha 6AX1X2 beta 4
      integrins also mediated cell adhesion to laminin and kalinin without stimulation.
      Furthermore, the different transfectants did not differ in their ability to
      spread on kalinin. The presented data indicate that the X2 region in alpha 6 is
      not involved in defining ligand specificity or affinity.

PMID- 7583008
TI  - Gastrulation in the sea urchin, Strongylocentrotus purpuratus, is disrupted by
      the small laminin peptides YIGSR and IKVAV.
AB  - Laminin is present on the apical and basolateral sides of epithelial cells of
      very early sea urchin blastulae. We investigated whether small laminin-peptides,
      known to have cell binding activities, alter the development of sea urchin
      embryos. The peptide YIGSR-NH2 (850 microM) and the peptide PA22-2 (5 microM),
      which contains the peptide sequence IKVAV (Tashiro et al., J. Biol. Chem. 264,
      16174, 1989), typically blocked archenteron formation when added to the sea water
      soon after fertilization. At lower doses, the YIGSR peptide allowed invagination
      of the archenteron but blocked archenteron extension and differentiation and
      evagination of the feeding arms. The effect of YIGSR and PA22-2 peptides declined
      when added to progressively older stages until no effect was seen when added at
      the mesenchyme blastula stage (24 hours after fertilization). Control peptides
      GRGDS, YIGSE, and SHA22, a dodeca-peptide with a scrambled IKVAV sequence, had no
      effect on development. The YIGSK peptide containing a conserved amino acid
      modification had only a small effect on gastrulation. The results suggest that
      YIGSR and IKVAV peptides specifically disrupt cell/extracellular matrix
      interactions required for normal development of the archenteron and feeding arms.
      Our recent finding that YTGIR is at the cell binding site of the B1 chain of S.
      purpuratus laminin supports this conclusion. Evidently, laminin or other laminin
      like molecules are among the many extracellular matrix components needed for the
      invagination and extension of the archenteron during the gastrulation movements
      of these embryos.

PMID- 7583010
TI  - Memory for brief, widely spaced odor presentations in the rat.
AB  - Rats trained on a series of 16 novel 2-odor discrimination tasks using a 10-s
      intertrial interval (ITI) rapidly improved in performance and made only 0-3
      errors by the end of the test series. They were then tested on other novel pairs
      of odors, but with a 10- and a 30-min interval between trials. There was no
      decrement in performance accuracy in the longer ITI tests and, in most cases,
      criterion performance was achieved after making zero or 1 error after the first
      (information) trial. These results demonstrate that rats have the capacity to
      remember for at least 30 min whether a single brief presentation of a novel odor
      was followed by a reward.

PMID- 7583009
TI  - An examination of focal adhesion formation and tyrosine phosphorylation in
      fibroblasts isolated from src-, fyn-, and yes- mice.
AB  - As cells adhere to extracellular matrix proteins, several focal adhesion proteins
      become tyrosine phosphorylated. One of the most prominent of these has been
      identified as the tyrosine kinase p125FAK (focal adhesion kinase, FAK). An
      interaction between FAK and members of the Src family tyrosine kinases p59fyn,
      pp60v-src, and activated pp60c-src (527F) has been demonstrated, raising the
      possibility that these kinases may regulate FAK activity. To explore the role of
      Src family kinases in focal adhesions and in the regulation of FAK activity, we
      isolated fibroblasts from transgenic mice that lack either pp60c-src, p59fyn, or
      pp62c-yes. These primary fibroblasts, and those of a control mouse, were passaged
      numerous times and resulted in spontaneously immortalized cell lines without the
      addition of transforming agents. After confirming the absence of the appropriate
      nonreceptor tyrosine kinases in the fyn-, src- and yes- fibroblasts, the ability
      of these fibroblasts to form focal adhesions and stress fibers was assessed by
      immunofluorescence microscopy and found to be comparable to that of normal
      fibroblasts. We investigated phosphotyrosine levels in response to adhesion to
      fibronectin and identified the pp60src substrate p130 as the one major protein
      with reduced levels of tyrosine phosphorylation in the cells lacking p59fyn and
      pp62c-yes, and particularly in those lacking pp60c-src. We examined FAK
      phosphorylation and kinase activity and found that there were no significant
      differences between these cells.

PMID- 7583012
TI  - G-protein subunits expressed in catfish olfactory receptor neurons.
AB  - Olfactory signal transduction in a number of species has been shown to be
      mediated by heterotrimeric GTP-binding proteins (G-proteins). The expression of
      different G-proteins in channel catfish (Ictalurus punctatus) olfactory
      epithelium was investigated using antibodies to both the alpha and beta subunits
      of G-proteins. Based on Western blotting and immunohistochemical data, the
      following G-protein subunits were identified in the olfactory epithelium:
      Gs/G(olf), Gi1, Gi2, Gq and G beta. Immunohistochemical results indicated that
      all of these G-proteins, encompassing three G-protein subfamilies, were expressed
      in the dendrites and cilia of olfactory receptor neurons. These findings suggest
      that different G-protein subunits may mediate multiple signal transduction
      pathways in the catfish olfactory system, i.e. G(olf)/Gs, may mediate odorant
      activation of adenylyl cyclase while Gi and G beta may mediate odorant activation
      of phospholipase C.

PMID- 7583011
TI  - Relative sensitivity of the ocular trigeminal, nasal trigeminal and olfactory
      systems to airborne chemicals.
AB  - We measured thresholds for eye irritation and odor in homologous series of
      alcohols (ethanol, 1-butanol, 1-hexanol and 1-octanol), ketones (2-propanone, 2
      pentanone, 2-heptanone and 2-nonanone), and alkylbenzenes (toluene, ethyl benzene
      and propyl benzene). Eye irritation thresholds were well above odor thresholds
      for all series. Both sensory thresholds declined with carbon chain length, a
      trend that has implicated lipophilicity in the potency of these and related
      stimuli. Eye irritation thresholds were remarkably close to nasal pungency
      thresholds obtained previously in persons lacking olfaction (i.e. anosmics). The
      agreement between the two thresholds implies that, despite differences in the
      mucus layer at the two sites and in the epithelial tissue itself, there is
      remarkable similarity at the site of stimulation. As a practical matter, the eyes
      could serve as the sites to assess potency for induction of nasal pungency, an
      assessment previously limited to testing anosmics. Presumably, for our brief
      stimulus presentations (1-3 s), the differences between ocular and nasal mucosae
      have little relevance to chemical sensitivity. Studies of the ability of
      homologous chemical series to evoke threshold eye irritation, nasal pungency and
      odor not only have practical value, but also can help to define the
      physicochemical properties of the receptor and perireceptor biophases.

PMID- 7583013
TI  - Garlic ingestion by pregnant women alters the odor of amniotic fluid.
AB  - Amniotic fluid samples were obtained from 10 pregnant women undergoing routine
      amniocentesis procedure. Approximately 45 min prior to the procedure, five of the
      women ingested placebo capsules, whereas the remaining five ingested capsules
      containing the essential oil of garlic. Randomly selected pairs of samples, one
      from a woman who ingested garlic and the other from a woman who ingested placebo
      capsules, were then evaluated by a sensory panel of adults. The odor of the
      amniotic fluid obtained from four of the five women who had ingested the garlic
      capsules was judged to be stronger or more like garlic than the paired samples
      collected from the women consuming placebo capsules. Thus, garlic ingestion by
      pregnant women significantly alters the odor of their amniotic fluid.

PMID- 7583014
TI  - Prediction of sweetness intensity for equiratio aspartame/sucrose mixtures.
AB  - The Equiratio Mixture Model predicts the responses to a series of equiratio
      mixtures on the basis of the psychophysical functions for the unmixed components.
      The model predicts the sweetness of mixtures of sugars and sugar-alcohols
      successfully, but is unable to predict mixture intensity for substances with
      different dynamic ranges. In this paper, the equi-intensity concept is introduced
      in the Equiratio Mixture Model by transforming the physical concentrations
      expressed in molarity into units that produce approximately equi-intense
      sensations. An empirical test using aspartame/sucrose mixtures shows that the
      modified Equiratio Mixture Model yields good predictions of mixture intensities.

PMID- 7583015
TI  - Endocrine, gonadal and behavioral responses of male crucian carp to the hormonal
      pheromone 17 alpha,20 beta-dihydroxy-4-pregnen-3-one.
AB  - The olfactory-mediated responses to the sex hormone 17 alpha,20 beta-dihydroxy-4
      pregnen-3-one (17 alpha,20 beta-P) were studied in spermiated and regressed male
      crucian carp (Carassius carassius L.). The position and spontaneous locomotor
      activity of single male crucian carp were continuously recorded in an artificial
      stream. 17 alpha,20 beta-P (final concentration 10(-11) M) was supplied to one
      half and its ethanol carrier to the other half of the test area. Milt volume and
      gonadotropin (GtH-II) concentration in the plasma were also measured. The smell
      of 17 alpha,20 beta-P significantly increased both the GtH-II concentration in
      the plasma and the volume of strippable milt in spermiated crucian carp.
      Behaviorally, the side of the test area scented with 17 alpha,20 beta-P was
      significantly avoided by spermiated males. None of the described effects of 17
      alpha,20 beta-P on spermiated males were observed for the regressed crucian carp.
      In view of the lack of response from regressed crucian carp we suggest that the
      observed avoidance behavior of 17 alpha,20 beta-P by spermiated males is a
      relevant reaction for spawning male crucian carp. The results are well in
      accordance with responses obtained in the closely related goldfish and gives
      strong support that the wild male crucian carp use the 17 alpha,20 beta-P signal
      from the females to prepare for the coming spawning.

PMID- 7583016
TI  - Cytochemical localization of guanylyl cyclase activity in rabbit taste bud cells.
AB  - Guanylyl cyclase activity was cytochemically demonstrated in rabbit foliate taste
      buds. The enzymatic activity was localized in the apical portion (microvilli and
      neck) of taste bud cells. Especially strong activity was observed on the
      microvillous membrane of type I (dark) cells and often on a blunt process of type
      III cells. The microvilli of type II (light) cells showed weak enzymatic
      activity. Considering that the apical portion of taste cells is a likely site of
      interaction between taste stimuli and the cells, the results support the idea
      that cyclic GMP is involved in taste transduction.

PMID- 7583018
TI  - Gene expression in neuronal activity.

PMID- 7583017
TI  - Activity and stability of a new sweet protein with taste-modifying action,
      curculin.
AB  - Curculin elicited a sweet taste. After the sweetness of curculin diminished,
      application of deionized water or an acid to the tongue induced a sweet taste.
      The maximum sweetness of curculin itself was equivalent to the sweetness of 0.35
      M sucrose. The maximum sweetness induced by 0.02 M citric acid or deionized water
      after curculin dissolved in a buffer of pH 6.0 was held in mouth for 3 min was
      also equivalent to that of 0.35 M sucrose. The sweetness induced by deionized
      water was completely suppressed by the presence of 1 mM CaCl2 or MgCl2, while
      that induced by an acid was not suppressed by the presence of divalent cations.
      Based on these results, the mechanism of the taste-modifying activity was
      discussed. Stability of curculin was examined under various conditions. The taste
      modifying activity of curculin was unchanged when curculin was incubated at 50
      degrees C for 1 h between pH 3 and 11.

PMID- 7583021
TI  - The olfactory system as a model for the analysis of the contribution of gene
      expression to programmed cell death.
AB  - The process of programmed cell death is frequently attenuated by inhibitors of
      protein and RNA synthesis. This implies that gene expression is necessary for the
      active elimination of some cell types. Genes such as bcl-2 and bax have been
      implicated in the direct control of cell death, while cellular immediate-early
      genes (cIEGs), such as c-fos and c-jun have been repeatedly associated with
      neuronal degeneration. We are using the olfactory neuroepithelium as a model
      system to investigate the role that expression of such genes might play in cell
      death. The advantages of this system is that even in the adult, there is
      spontaneous degeneration of olfactory receptor neurons followed by their
      replacement by the division and differentiation of precursors. Furthermore, the
      receptor neurons can be induced to die synchronously by removal of the olfactory
      bulb or intranasal administration of toxic agents. We have generated fos-lacZ and
      jun-lacZ transgenic mice that can be used to assess expression of c-fos and c-jun
      following these various manipulations. In addition, a line of transgenic mice has
      been derived that express Bcl-2 under the control of the olfactory receptor
      protein promoter. These mice have high levels of Bcl-2 selectively in receptor
      neurons of the primary neuro-epithelium and vomeronasal organ. Since in some
      circumstances, Bcl-2 can protect against programmed cell death these mice are
      being assessed for neuronal turnover under basal conditions and following
      olfactory bulbectomy.

PMID- 7583020
TI  - Dopamine regulation of transcription factor-target interactions in rat striatum.
AB  - Transcriptional regulation is an important mechanism by which neurons adapt to
      environmental stimuli. The indirect dopamine agonists, amphetamine and cocaine
      have been shown to induce expression of immediate early genes, such as c-fos, and
      neuropeptide genes, such as prodynorphin in the rat striatum. Here we show that
      phosphorylation of transcription factor CREB is a critical early event coupling
      dopamine stimulation to gene regulation. CREB interacts with functional
      regulatory elements in both the c-fos and prodynorphin genes, and is
      phosphorylated in response to dopamine in a D1 dopamine receptor-dependent
      manner. In addition, we show by intra-striatal injection of antisense
      oligonucleotides directed against CREB mRNA, that CREB protein is required for c
      fos induction by amphetamine.

PMID- 7583019
TI  - The glucocorticoid receptor synergizes with Jun homodimers to activate AP-1
      regulated promoters lacking GR binding sites.
AB  - Jun/Fos (AP-1) and steroid hormone receptors (SHR) are distinct families of
      transcription factors that convert extracellular signals into long-term genetic
      responses. Despite clear differences in their modes of activation and DNA binding
      specificities, a regulatory cross-talk between AP-1 and SHR such as the
      glucocorticoid receptor (GR), has been established. Here, we show that the
      hormone-activated GR negatively or positively modulates the expression of AP-1
      dependent genes, depending on the subunits of the dimeric AP-1 complex. This type
      of regulation does not depend on the presence of a GR binding site in the
      promoter and is mediated through the DNA binding domain of Jun. Since individual
      subunits of AP-1 exhibit small differences in sequence specificity, specific
      subsets of AP-1-dependent genes may be regulated by steroid hormones in different
      directions.

PMID- 7583022
TI  - Functional mapping of odor-activated neurons in the olfactory bulb.
AB  - Induction of immediate-early gene expression, in particular c-fos, can be used to
      map neural activity in many brain areas, including the olfactory system. By
      making use of the resolution provided by cellular localization of c-fos mRNA or
      Fos protein, those neurons activated by a particular odor stimulus can be
      identified. Odor presentation to awake rats increases c-fos expression by bulb
      neurons located in discrete portions of the glomerular layer and in the
      underlying mitral and granule cell layers. The translaminar distribution of co
      ordinately activated cells corresponds to the 'functional unit' predicted by the
      synaptic organization of the bulb, and the distribution of these units throughout
      the bulb as a whole differs for different odors. The bulbar pattern of activity
      is spatially altered by changes in odor intensity and during the course of
      postnatal development. These findings support the idea that distributed patterns
      of odor-induced neuronal activity contribute to the encoding of olfactory
      information. Moreover, the role of c-fos in the transcriptional regulation of
      other genes suggests a mechanism whereby odor experience can lead to long-term
      changes in the olfactory system.

PMID- 7583023
TI  - Congener-specific bioavailability of PCDD/Fs and coplanar PCBs in cows:
      laboratory and field measurements.
AB  - To estimate congener-specific bioavailabilities for 17 PCDD/Fs in cows grazing
      near a MSW incinerator both a controlled lab study and a field study were
      performed. In the lab study the estimates were derived from the elevated
      concentrations in milk from two cows after administration of a single dose of
      contaminated fly ash. In the field study, located near a large MSW incinerator,
      daily samples of grass and milk collected over a period of 60 days were pooled to
      two monthly bulk samples. The concentrations in these bulk samples of grass and
      milk were used to estimate the bioavailabilities of the 17 PCDD/Fs as well as of
      three coplanar PCBs. With the concentrations of PCDD/Fs expressed in I-TEQs the
      bioavailability in cows was estimated at +/- 7.5% in the field study. The
      congener-specific bioavailabilities correlated well between the two studies, as
      well as with previously reported values in the literature. However, the absolute
      levels differed considerably between studies, indicating a strong matrix effect.

PMID- 7583024
TI  - Recalcitrant organochlorine compounds in captive bottlenose dolphins (Tursiops
      truncatus): biomagnification or bioaccumulation?
AB  - Organochlorine residues were measured in the diet, blood, faeces and exhaled air
      of captive bottlenose dolphins (Tursiops truncatus) to evaluate the absorption
      efficiency from food and the eliminatory potential via faeces and exhaled air.
      Differences between air-breathing and water-breathing animals feeding on similar
      prey are briefly discussed. It is concluded that high concentrations of
      recalcitrant organochlorines currently found in marine mammals feeding on fish
      are essentially due to the lack of branchial elimination and not to their
      predator status.

PMID- 7583026
TI  - Open Nissen fundoplication.
AB  - The Nissen fundoplication currently is the most commonly used antireflux
      operation. It may be performed using a transabdominal or a transthoracic
      approach. Early postoperative complications are not infrequent and include
      dysphagia and the "gas bloat" syndrome. Excellent or good long-term results are
      obtained in more than 85% of patients.

PMID- 7583025
TI  - PCDD/PCDF levels in the blood of workers at a pulp and paper mill.
AB  - Blood samples from 34 workers at a pulp and paper mill and from 14 control
      persons were analysed for 2,3,7,8-substituted PCDDs and PCDFs. There were no
      statistically significant differences in total lipid-adjusted PCDD/PCDF
      concentrations, expressed as toxic equivalents, in blood plasma between the
      potentially exposed bleaching plant or paper mill workers and the controls. The
      mean level was 61 pg/g I-TEQ in bleaching plant workers, 60 pg/g I-TEQ in paper
      mill workers and 49 I-TEQ pg/g in controls. Regarding the concentrations of
      individual isomers, however, there was an indication that the blood plasma
      concentrations might be affected by the living and working environment.

PMID- 7583027
TI  - Belsey Mark IV antireflux procedure.
AB  - The unmodified version of the Belsey Mark IV antireflux procedure is described.
      Specific indications for use of this procedure to treat gastroesophageal reflux
      disease are listed. Patient preparation and anesthetic considerations are
      discussed.

PMID- 7583028
TI  - Hill antireflux operation.
AB  - There are multiple published reports of the efficacy of the Hill procedure in
      controlling problems with primary reflux, recurrent hiatal hernias, and failed
      previous operations, and in patients with reflux complicated by peptic esophageal
      stricture. There also are more recent reports demonstrating its applicability in
      laparoscopic antireflux operations. Currently, the longest follow-up study for
      patients undergoing antireflux surgery originated at the Virginia Mason Medical
      Center and was published in 1988. This review followed 167 patients for a minimum
      of 15 to 20 years (mean 17.8 years) following their Hill operations. This study
      demonstrated the durability of the Hill antireflux operation in that more than
      85% of patients were still completely satisfied with their postoperative results
      15 to 20 years following the operation. In 1993 the author and colleagues carried
      out a quality-of-life analysis 1 year following standard open antireflux surgery
      in 60 patients operated on between April 1991 and November 1992. Forty-nine of
      these patients underwent primary operations, whereas 11 (18%) were undergoing
      repeat operations. A prospective modified Visick-type classification as proposed
      by Dr. Pope was used and all patients were asked to prospectively rate their
      quality of life on a standard scale (from 0 = worst to 10 = best) preoperatively
      and then 1 year following operation. It was found that symptom scores on the
      modified Visick scale improved dramatically (Table 1) and that patients'
      individual perceptions of their quality of life were equally dramatically
      improved (see Table 1). We have found the Hill procedure to be highly effective,
      safe therapy for primary, recurrent, and complicated antireflux problems. The
      repair is durable in the long-term, and it can be applied laparoscopically. We
      have made some minor changes in surgical technique to make the procedure easier
      to understand and apply by all surgeons interested in treating patients with
      antireflux disease.

PMID- 7583029
TI  - Uncut Collis-Nissen gastroplasty.
AB  - Surgical treatment of gastroesophageal reflux because of an incompetent lower
      esophageal sphincter and obstructive symptoms owing to a partial or incomplete
      intrathoracic stomach has evolved tremendously over the past several decades.
      Currently, there are several different techniques to improve the abnormalities
      caused by these defects, of which the uncut Collis-Nissen gastroplasty is one.
      The operation has withstood the test of time and has low mortality, acceptable
      morbidity, and excellent short- and long-term results. More importantly, it is
      reproducible and is an operation that can be taught to others. The author
      believes the data continue to warrant the use of this procedure; however, it
      should be acknowledged that there is as yet no perfect procedure and continued
      modifications and analysis of long-term results are needed.

PMID- 7583030
TI  - The technique of laparoscopic Nissen fundoplication.
AB  - Patients with severe GERD resistant to medical therapy are benefited greatly by
      laparoscopic fundoplication provided that there is careful preoperative patient
      selection and evaluation. Preoperative evaluation should include contrast
      esophagography, EGD with biopsies, stationary manometry, and 24-hour pH analysis.
      Significant esophageal shortening or severe dysplasia are contraindications to
      laparoscopic fundoplication. A short, loose Nissen fundoplication should be
      performed in patients with adequate esophageal body function, whereas patients
      with esophageal dysmotility should be offered a partial fundoplication such as
      the Toupet procedure. If these guidelines are followed, long-term good results
      can be expected, with minimal complications, and all of the advantages of the
      minimally invasive approach.

PMID- 7583031
TI  - Pharyngoesophageal diverticulum: technique of repair.
AB  - Pharyngoesophageal diverticulum is an acquired defect resulting from an
      incoordination of the cricopharyngeal muscle. Common symptoms are dysphagia,
      regurgitation, and aspiration. The defect is repaired through a cervical incision
      and should include a diverticulectomy and a myotomy. Results are excellent and
      complications are unusual.

PMID- 7583032
TI  - Thoracoscopic Heller's myotomy. Treatment of achalasia by the videoendoscopic
      approach.
AB  - In summary, the authors believe that minimally invasive surgery has added a new
      dimension to the treatment of achalasia. Thoracoscopic myotomy is feasible, safe,
      and effective in relieving dysphagia in the great majority of individuals
      affected with this disease without the many problems associated with dilatation;
      thus, the authors offer it to patients with achalasia as the initial and
      preferred form of treatment. Whether an antireflux procedure should be routinely
      added and whether a laparoscopic rather than a thoracoscopic approach is
      preferred, remains unanswered questions at this time.

PMID- 7583033
TI  - Technique of esophageal dilation.
AB  - The widespread use of flexible upper gastrointestinal (GI) endoscopy has renewed
      interest in management of strictures of the esophagus, including dilation. The
      rubber Maloney dilator is the most common dilator used, usually for symmetrical
      strictures 1.2 cm or greater in diameter. The "through the scope" (TTS) balloon
      dilators usually are used in asymmetrical strictures 1.2 cm or greater in
      diameter and are especially valuable if fluoroscopy is not available. The new
      thermoplastic Savary dilators, used with a guidewire and usually with
      fluoroscopy, have replaced the Eder-Puestow bougies. They are especially useful
      in difficult strictures that are 1.0 cm or less in diameter and are fibrotic or
      have transmural fibrosis.

PMID- 7583034
TI  - Atkinson tube placement.
AB  - Endoscopic intubation of a malignant esophageal stricture with an endoprosthesis
      allows quick and adequate palliation for a patient with a very limited life span.
      The technique of Atkinson tube insertion is described and illustrated.
      Complications are discussed briefly.

PMID- 7583035
TI  - Thoracoscopic staging of esophageal carcinoma.
AB  - Thoracoscopy is an excellent complement to mediastinoscopy in staging thoracic
      malignancies. The author describes the technique of thoracoscopic and
      laparoscopic lymph node staging for patients with esophageal carcinoma.

PMID- 7583036
TI  - Ivor Lewis esophagectomy.
AB  - Lewis described a technique for resection of cancer of the midthoracic esophagus
      in a staged manner in 1946. The same procedure done at one stage has remained a
      standard technique for resection of a carcinoma involving the thoracic esophagus.

PMID- 7583037
TI  - Transhiatal esophagectomy.
AB  - Transhiatal esophagectomy (THE) with cervical esophogastric anastomosis avoids
      thoracotomy and the potential for sepsis from an intrathoracic anastomotic leak.
      Knowledge of anatomy, careful attention to details of the operation, and good
      judgment toward patient selection will allow THE to be a valuable tool in the
      surgical palliation of esophageal carcinoma.

PMID- 7583039
TI  - Use of colon and jejunum as possible esophageal replacements.
AB  - When the stomach is not available, the colon or the small bowel can act as
      appropriate replacement conduits for the esophagus. A short left colon or small
      bowel interposition is favored for a short conduit. A long, left colon
      interposition is recommended for a subtotal or total esophagectomy. A long-limb
      Roux-Y jejunum interposition is favored following a total gastrectomy. The
      ultimate goal should be to restore the function of swallowing with minimal
      morbidity and mortality.

PMID- 7583040
TI  - Medical genetics in Israel.
AB  - The state of Israel was founded in 1948 and includes approximately 4.5 million
      Jews and 1 million of non-Jews, mainly Muslim Arabs. Subgroups can be
      distinguished within each of these two groups: among the Jews according to their
      country of origin and among the non-Jews according to their religion or even
      their village of origin. The precise origin of each patient is particularly
      important for the medical geneticists since in each subgroup some hereditary
      disorders have been reported with an increased frequency. This knowledge also
      allows in some cases for preventive genetic screening. The reasons for the
      relatively high frequency of mendelian disorders in the different communities in
      Israel are numerous including mainly a founder effect with genetic drift and
      selection. In Israel, medical genetics is a recognized medical speciality and
      there are eleven clinical genetic centers in the country. These centers are in
      close contact with the individuals active in the different fields of human
      genetics in Israel both for service and research.

PMID- 7583038
TI  - Left transthoracic esophagectomy.
AB  - Left transthoracic esophagectomy remains an important option in performing
      esophagectomy. This is especially appropriate for malignancies of the distal
      esophagus and gastroesophageal (GE) junction. Likewise, resections in patients
      who have had prior surgery at the GE junction are easily performed through the
      left chest. The technical details of left transthoracic esophagectomy are
      described and illustrated.

PMID- 7583041
TI  - Physical mapping evidence for a duplicated region on chromosome 10qter showing
      high homology with the facioscapulohumeral muscular dystrophy locus on chromosome
      4qter.
AB  - p13E-11, a probe (D4F104S1 locus) derived from chromosome 4q35, detects EcoRI
      rearranged fragments less than 28 kb in both sporadic and familial cases of
      facioscapulohumeral muscular dystrophy (FSHD). These fragments are smaller than
      those observed in healthy individuals. The interpretation of Southern blots is
      complicated by the fact that p13E-11 reveals two pairs of polymorphic alleles,
      one 4q35-specific and the other unlinked to 4q35, that sometimes overlap each
      other. We cloned a non-4q35 13-kb fragment not related to the disease from a
      sporadic FSHD patient of Italian origin. Haplotype analysis and in situ
      hybridization experiments showed that this fragment was located on the 10qter
      region. Restriction mapping of the 10qter clone, when compared with the 4q35
      fragment, indicates a similar arrangement of KpnI tandemly repeated units and
      flanking sequences. However 4q35 and 10q26 EcoRI clones can be distinguished by
      restriction analysis with SfiI and StyI. This observation could be exploited for
      future applications in the field of molecular diagnosis and genetic counseling.
      In addition the isolation of two 10q26 cosmid clones (D10S1484 and D10S1485) from
      a human genomic library and the construction of a detailed physical map, spanning
      about 40 kb, showed that the structural homology extended upstream of the EcoRI
      sites, suggesting that a duplicated FSHD locus resided in the subtelomeric region
      of the long arm of chromosome 10. We cannot exclude the involvement of the
      duplicated locus in the molecular mechanism of the disease and in the genetic
      heterogeneity of FSHD syndromes.

PMID- 7583042
TI  - Expression of the human Dp 71 (apo-dystrophin-1) gene from a 760-kb DMD-YAC
      transferred to mouse cells.
AB  - A 760-kb YAC was constructed by homologous recombination in yeast, containing the
      genes located in the distal portion of the DMD gene. The YAC was introduced in
      mouse LA-9 cells by PEG-mediated cell fusion. One transformant accommodated an
      intact DMD-YAC, i.e. a full copy of the DMD internal Dp 116, Dp 71 and Dp 40
      genes (apo-dystrophin-2, -1 and -3, respectively). We have studied the expression
      of the various gene products derived from the introduced DMD-YAC. RT-PCR revealed
      expression of human Dp 71 but not of Dp 116 or Dp 40. Remarkably, differences
      were observed in processing of the 3' region of the endogenous mouse and the
      human transcripts, due to different splicing of exons 71 (absent in human and
      present in mouse transcript) and 78 (present in human and absent in mouse
      transcript). The splicing pattern of the human transcript is the same as that of
      the major Dp 71 (apo-dystrophin-1) product in human blood. The observed splicing
      differences may be caused by either species-specific exon use and/or by cis
      acting factors, e.g. the upstream transcript composition, because we have no
      evidence for endogenous Dp 71 expression.

PMID- 7583043
TI  - An integrated map of human chromosome 13 allowing regional localization of
      genetic markers.
AB  - 37 CA repeats, 5 STSs, 9 ESTs, and 4 genes were mapped to 19 different intervals
      of chromosome 13 determined by the cytogenetic breakpoints of 19 different cell
      lines with interstitial deletions or translocations involving various parts of
      chromosome 13. A framework genetic linkage map was constructed from 25 of these
      microsatellite markers, to which 26 markers from other genetic maps were added.
      Thus, an integrated map of chromosome 13 resulted. Since the microsatellite
      markers included in this study derive from different genetic maps, an approximate
      regional localization can now be assigned in principle to any genetic marker on
      chromosome 13.

PMID- 7583044
TI  - A genetic map of chromosome 11q, including the atopy locus.
AB  - Atopy is a common and genetically heterogeneous syndrome predisposing to allergic
      asthma and rhinitis. A locus linked to the atopy phenotype has been shown to be
      present on chromosome 11q12-13. Linkage has only been seen in maternally derived
      alleles. We have constructed a genetic linkage map of the region, using 15
      markers to span approximately 27 cM, and integrate previously published maps.
      Under a model of maternal inheritance, the atopy locus is placed within a 7-cM
      interval between D11S480 and D11S451. The interval contains the important
      candidate gene FCERIB.

PMID- 7583045
TI  - Convergent myotonic dystrophy (DM) haplotypes: potential inconsistencies in human
      disease gene localization.
AB  - Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease which has
      been shown to be caused by an unstable trinucleotide repeat located on chromosome
      19q. We have conducted extensive haplotype analysis on 105 DM chromosomes using
      twelve 19q13.2 loci identifying 18 RFLPs, spanning a physical distance of 1.3 Mb
      containing the DM gene. Three major haplotypes (H1, H2 and H3) comprising 46.7%
      of the DM chromosomes in our population, were observed. With the exception of H1
      and H2 derivatives (H4, H5 and H6), the remainder of the DM chromosomes analyzed
      were found to have unique haplotypes. Haplotypes H2 and H3 observed exclusively
      on DM chromosomes of French-Canadian origin contain identical 500-kb core
      regions. The low frequency of this core haplotype in normal chromosomes (0.8%) is
      consistent with a mapping of the DM gene within this region. However, the DM
      mutation is found 160 kb distal to the point of divergence between the two
      haplotypes. In contrast, the 450-kb region shared by haplotypes H1 and H2
      contains the DM mutation. Further analysis of the DM region using a polymorphic
      microsatellite (GJ-VSSM2; D19S207) located 15 kb distal to the DM mutation
      revealed strong allelic association of one of the (CA)n repeat alleles to DM;
      allele 5 was observed on 88.2% of DM chromosomes and 6% of normal chromosomes.
      The fact that the (CA)n allele 5 was found on all 56 DM chromosomes containing
      the three major haplotypes indicates that DM chromosomes in our population,
      including the two French-Canadian haplotypes which have a common region outside
      the DM gene, are probably derived from the same mutational event.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7583046
TI  - Detection of homozygosity by descent.

PMID- 7583048
TI  - Podocyte architecture in puromycin aminonucleoside-treated rats administered
      tungsten or allopurinol.
AB  - The role of xanthine oxidase as a source of reactive oxygen species in puromycin
      aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine
      oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and
      tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell
      ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and
      urinary protein excretion were examined in puromycin aminonucleoside-treated
      rats. Co-administration of allopurinol to such rats reduced proteinuria by
      approximately 70% over the 10 days studied, and reduced the degree of glomerular
      epithelial cell foot process effacement at both 5 and 10 days, compared to rats
      that received puromycin aminonucleoside alone. Unexpectedly, co-administration of
      allopurinol to puromycin aminonucleoside-treated rats did not reduce xanthine
      oxidase activity; however, the combined activity of xanthine oxidase and xanthine
      dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten
      to puromycin aminonucleoside-treated rats did not reduce proteinuria or alter the
      number of filtration slits. Rats co-administered tungsten and puromycin
      aminonucleoside had significantly reduced renal xanthine oxidase and combined
      xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared
      to rats treated with puromycin aminonucleoside alone. These results provide
      evidence that the protection provided by allopurinol in puromycin aminonucleoside
      treated rats is due to the antioxidant properties of allopurinol, rather than to
      its activities as a xanthine oxidase inhibitor.

PMID- 7583047
TI  - Gene defect in polycystic kidney disease.

PMID- 7583049
TI  - Furosemide treatment alters the distribution of kallikrein gene expression in
      kidneys of mice.
AB  - The renal kallikrein gene is normally expressed in convoluted distal and
      connecting tubules of the renal cortex. After furosemide treatment of mice there
      was strong expression also in the distal thick ascending limb of the loop of
      Henle in the renal outer medulla. This expansion of the kallikrein-expressing
      distal tubule cell population did not occur in mice on a sodium-restricted diet,
      in sodium-restricted mice given a high potassium diet or in untreated controls.
      Although the overall level of kallikrein gene expression was significantly
      greater in kidneys from furosemide-treated mice than in any other group, there
      was no detectable change in renal kallikrein gene expression in the submandibular
      glands after any of the treatments.

PMID- 7583050
TI  - 1,25-Dihydroxycholecalciferol stimulates the expression of intercellular adhesion
      molecule-1 in renal carcinoma cells.
AB  - 1,25-Dihydroxycholecalciferol (1,25-D3) is a potent immunomodulatory vitamin
      modulating major histocompatibility complex class-II expression in monocytes and
      epithelial cells. However, the impact of 1,25-D3 on the expression of adhesion
      molecules in epithelial cells has not been investigated. Human renal tubular
      epithelial and renal carcinoma cells express intercellular adhesion molecule-1
      (ICAM-1), a ligand of the leukocyte-function-associated antigen-1 (LFA-1).
      Therefore, we addressed the question whether 1,25-D3 modulates ICAM-1 expression
      by renal carcinoma cells. Using an enzyme-linked immunoassay we detected an
      increase in ICAM-1 expression by a renal carcinoma cell line (ACHN) cultured in
      the presence of 1,25-D3. Also, in ACHN cells stimulated with gamma-IFN a
      significant stimulatory effect of 1,25-D3 was evident. ICAM-1 is crucial for the
      adhesion of LFA-1-expressing lymphocytes and is involved in antigen presentation.
      In addition, ICAM-1 may be of significance in lymphocyte lysis of tumor cells.
      Therefore, the impact of 1,25-D3 on ICAM-1 expression by renal and non-renal and
      non-renal carcinoma cells and renal tubular epithelial cells may be of clinical
      importance.

PMID- 7583051
TI  - Effects of antihypertensive therapy on blood pressure and renal function in rats
      with hypertension due to chronic blockade of nitric oxide synthesis.
AB  - Different antihypertensive treatment regimes were studied in rats during long
      term inhibition of nitric oxide synthesis. Male Munich Wistar rats (weight 150
      200 g) were put on oral L-nitro-arginine methyl ester (L-NAME, 50 mg/l drinking
      water) for 12 weeks. The control group (n = 16) received only tap water. Six
      weeks after starting L-NAME administration rats were divided into 7 groups (n =
      13 in each group: group 1, no treatment; group 2, l-arginine 1 g/l drinking
      water; group 3, doxazosin 30 mg/kg/day; group 4, felodipine 25-30 mg/kg/day;
      group 5, losartan 40 mg/kg/day; group 6, metoprolol 300-350 mg/kg/day, and group
      7, ramipril 1 mg/kg/day. Systolic blood pressure (sBP) was measured in the
      conscious rat 1, 6, and 12 weeks after study begin. After a treatment period of 6
      weeks albuminuria, glomerular filtration rate (GFR) and renal plasma flow (RPF;
      inulin and p-aminohippuric acid clearance) were analyzed. All rats showed a
      significant increase in sBP under 6 weeks of L-NAME administration. Control rats
      remained normotensive during the whole study period. Rats receiving L-NAME
      without antihypertensive treatment showed a further increase in sBP after 12
      weeks. Blood pressure was lowered in all treated animals, except in rats
      receiving l-arginine. Values for GFR were lowest in the placebo group, the l
      arginine group and in rats receiving felodipine (p < 0.05 compared to the control
      group). RPF was lowest in the placebo group, the l-arginine group, the felodipine
      group and the ramipril group (p < 0.05 compared to the control group).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7583052
TI  - Response to mucosal antigen challenge in IgA nephropathy.
AB  - While IgA nephropathy (IgAN) is characterized by the deposition of glomerular
      IgA, the source of the deposited IgA is not known, with both the mucosal and
      systemic IgA systems being implicated. In order to investigate mucosal and
      systemic antibody production to mucosal antigen challenge in IgAN, 9 patients and
      11 controls were immunized intranasally with tetanus toxoid (TT). There was no
      significant difference in the serum or saliva IgG, IgA, IgA1, or IgA2 antibody
      production to TT. However, in IgAN there was an increase of in vitro IgA anti-TT
      production in Epstein-Barr virus transformed cultures of peripheral blood
      lymphocytes taken after mucosal immunization. This increase in traffic of
      immunocompetent cells between the systemic and mucosal systems could play a role
      in the link between the mucosa and glomerulus in IgAN. Systemic immunization with
      TT following mucosal priming did not result in any difference in the antibody
      response between patients and controls. There was no evidence from this study
      that mucosal immunization results in an enhanced antibody response in IgAN or
      that mucosal priming alters the subsequent systemic antibody response.

PMID- 7583053
TI  - Myofibroblasts and the progression of experimental glomerulonephritis.
AB  - We have studied the sequential morphological changes that took place in the
      kidneys of 8 rats with nephrotoxic serum nephritis (NTN). Rats underwent kidney
      biopsies at different time intervals (days 7, 15, 30, 90 and 120). The tissues
      were processed for light microscopy as well as immunohistochemistry for
      inflammatory cellular infiltrate as well as for the components of the
      extracellular matrix (ECM) and myofibroblasts (cells expressing alpha-smooth
      muscle actin, alpha-SMA). Nephrotic rats developed severe proteinuria, impaired
      renal function as well as progressive renal scarring. However, the natural
      history of NTN was heterogeneous with some rats recovering (n = 5) and other
      progressing to end-stage renal failure (n = 3). The heterogeneous nature of the
      glomerulonephritis has established that those with a good outcome had a
      stabilisation, with some resolution, of the deposited ECM and of the scarring
      process. By contrast, rats with a poor outcome had a progressive increase in
      glomerular as well as interstitial ECM. Cells expressing alpha-SMA
      (myofibroblasts) were detected in the glomeruli as well as in the interstitium of
      nephritic rats. Changes in the expression of cells expressing alpha-SMA
      paralleled those of the components of the ECM in particular fibronectin. alpha
      SMA immunostain was the best predictor of progression. Early glomerular alpha-SMA
      immunostain (days 7 and 30) was a strong predictor of the subsequent development
      of glomerulosclerosis and renal dysfunction. The predictive value of interstitial
      alpha-SMA immunostain on days 7 for subsequent tubulo-interstitial scarring and
      renal insufficiency was also strong and exceeded that of other histological or
      immunohistochemical parameters of scarring. This study establishes the natural
      history of experimental renal scarring and identifies a renal cell type, the
      myofibroblast, as a useful marker of progression. It also suggests a role for
      myofibroblasts in the progression of glomerulosclerosis and tubulo-interstitial
      fibrosis.

PMID- 7583054
TI  - 14N nuclear quadrupole resonance studies of 1,8-bis(dimethylamino)naphthalene.
AB  - The presence of four resonance peaks from two nitrogen atoms in the 14N nuclear
      quadrupole resonance (NQR) spectrum of 1,8-bis(dimethylamino)naphthalene (DMAN)
      confirms the asymmetry of this molecule in the crystal. Spectroscopic parameters
      such as transition frequencies as well as the asymmetry parameters of the
      electric field gradient (EFG) tensors and differences in sigma bond occupation
      numbers have been assigned to particular nitrogen atoms in the molecule.

PMID- 7583055
TI  - Titanium carbide, nitride and carbonitrides: a 13C, 14N, 15N and 47,49Ti solid
      state nuclear magnetic resonance study.
AB  - The first 47,49Ti, 13C, 14N and 15N solid-state nuclear magnetic resonance (NMR)
      spectra of titanium carbide, nitride and a series of cubic carbonitrides have
      been obtained under both static and magic-angle spinning (MAS) conditions. The
      15N samples were isotopically enriched by gas-solid exchange at 1000 degrees C in
      a closed system. The Ti spectra of the carbide and nitride are sharp, reflecting
      the well defined cubic symmetry of these compounds, but become considerably
      broadened in the carbonitride series, with the spectra being approximately the
      sum of TiC and TiN together with some small electric field gradient (EFG)
      effects. The resonance positions and widths of all the NMR spectra change as
      carbon is progressively replaced by nitrogen. A relationship is observed between
      the 13C chemical shift and the nitrogen content of the carbonitrides, suggesting
      a possible NMR method for estimating the composition of these compounds. Although
      electron paramagnetic resonance (EPR) spectra of all these compounds show
      typically metallic behaviour, the NMR spectra show few effects attributable to
      conduction electrons, probably due to the lack of s-orbital contributions to the
      conduction band.

PMID- 7583056
TI  - Spin relaxation studies of pyrene by 13C nuclear magnetic resonance spectroscopy.
AB  - The effect of the repetition and contact times on the intensity of the magic
      angle spinning (MAS) spectra of pyrene has been studied. Pyrene, like a great
      number of fused polyaromatic compounds, has a very large 13C longitudinal
      relaxation time (T1Z). When using the cross-polarization (CP) MAS technique, the
      optimum repetition time is 800 s. The simulation of the central line of the
      pyrene CP-MAS spectra allowed us to determine the chemical shift of each carbon
      in the solid state. As the T1Z (13C of the total spectrum) of pyrene was observed
      to be 1780 s, attempts have been made to relax it by the addition of
      chromium(III) acetylacetonate or by supporting it on a carrier of gamma-Al2O3:
      the mixing of chromium(III) acetylacetonate to pyrene by solid mixing, or
      solution mixing followed by evaporation of the solvent, has no effect on its
      relaxation time; the Haldor Topsoe TK551 catalyst, a gamma-alumina supported Ni
      Mo-P catalyst, has been found to be a very efficient spin relaxation agent for
      the products adsorbed on it. For example, at 25 degrees C, the 10 wt.-% pyrene
      TK551 catalyst is 3 x 10(4) times more relaxed than pure pyrene.

PMID- 7583058
TI  - Variable-angle double rotation technique: a new two-dimensional high-resolution
      technique for quadrupolar nuclei.
AB  - We describe a new two-dimensional high-resolution technique for nuclei with semi
      integer spins subjected to strong quadrupole interactions. This variable-angle
      double rotation (VADOR) technique separates anisotropic spectral patterns
      according to the isotropic shift of each species. No sudden sample reorientation
      is needed for VADOR which can consequently be used regardless of the "relaxation
      times". This technique can also be utilized to characterize slow molecular
      reorientations in two- or three-dimensional experiments. We also propose a new
      geometry for DOR probes (theta e = 70.124 degrees, theta i = 54.736 degrees)
      which suppresses first-order interactions (chemical shift anisotropy and dipolar)
      more efficiently than the geometry (theta e = 54.736 degrees, theta i = 30.556
      degrees) presently employed.

PMID- 7583060
TI  - Molecular motions in solid estradiol studied by nuclear magnetic resonance
      spectroscopy.
AB  - The temperature dependence of the proton nuclear magnetic resonance (NMR)
      relaxation time T1 and second moment M2 of polycrystalline beta-estradiol
      hemihydrate (1,3,5-estratriene-3,17 beta-diol) is measured at frequencies of 14
      and 25 MHz. Below 260 K relaxation is found to be dominated by C3 reorientation
      of the single methyl group in each molecule, characterized by an activation
      energy of 9.4 +/- 0.1 kJ/mol. Above 260 K another relaxation mechanism becomes
      evident, characterized by an activation energy of 22 +/- 2 kJ/mol and ascribed to
      motion of the water molecules in the solid.

PMID- 7583059
TI  - 71Ga and 69Ga nuclear magnetic resonance study of beta-Ga2O3: resolution of four-
      and six-fold coordinated Ga sites in static conditions.
AB  - 71Ga and 69Ga nuclear magnetic resonance (NMR) spectra have been obtained for
      beta-Ga2O3 at magnetic fields of 11.7 and 7.0 T with a combination of static and
      spinning samples and using echo techniques. Isotropic chemical shifts and well
      constrained electric field gradient (EFG) tensors were measured for the GaIV and
      GaVI sites in beta-Ga2O3 and are reported for the first time. Due to its high
      quadrupolar coupling constant the GaIV site in beta-Ga2O3 is only resolved in
      static conditions. Analysis of spectral discontinuities obtained for different
      isotopes and magnetic field strengths and a method of readily obtaining very
      broad spectra without point by point acquisition demonstrate an approach that
      should be very useful in constraining the chemical shifts and quadrupole
      parameters involved in solid-state gallium NMR spectra.

PMID- 7583061
TI  - Fractional power time dependence of the nuclear magnetization in the presence of
      paramagnetic impurities.
AB  - We extend the theory of growth of the nuclear magnetization in the presence of
      paramagnetic impurities and the absence of spin diffusion to the case of multi
      paramagnetic centers. We show that for short times after saturation pulses, the
      rate of growth of the magnetization is proportional to t alpha where t is the
      time and alpha = 1/3, 1/2 and 2/3 for one-, two- and three-dimensional systems,
      respectively. We also present experimental data for which the total time
      dependent magnetization is proportional to exp[-(t/T1) alpha], which reduces to
      the above time dependence for short times.

PMID- 7583057
TI  - Empirical compensation function for eddy current effects in pulsed field gradient
      nuclear magnetic resonance experiments.
AB  - An empirical compensation function for the correction of eddy current effects in
      the Stejskal-Tanner pulsed-gradient spin-echo (PGSE) nuclear magnetic resonance
      (NMR) experiments has been established. Eddy currents may arise as a result of
      the application of sharp and strong gradient pulses and may cause severe
      distortion of the NMR signals. In this method, the length of one gradient pulse
      is altered to compensate for the eddy current effects. The compensation is
      considered to be ideal when the position and the phase of the spin-echo maximum
      obtained from an aqueous solution of poly(ethylene glycol) (PEG) is the same in
      the presence and absence of a gradient pulse in the PGSE pulse sequence. We first
      characterized the functional dependence of the length of the required
      compensation on the three principal variables in the PGSE experiment: the
      gradient strength, the duration of the gradient pulse, and the interval between
      the two gradient pulses. Subsequently, we derived a model which successfully
      describes the general relationship between these variables and the size of the
      induced eddy current. The parameters extracted from fitting the model to the
      experimental compensation data may be used to predict the correct compensation
      for any combination of the three principal variables.

PMID- 7583062
TI  - Separating subspectra from cross-polarization magic-angle spinning nuclear
      magnetic resonance spectra by proton spin relaxation editing.
AB  - Differences in proton spin relaxation time constants can be exploited to edit
      cross-polarization magic-angle spinning nuclear magnetic resonance (CP-MAS NMR)
      spectra of heterogeneous mixtures of different types of organic matter. This
      paper describes an extension of the editing procedure from two-component to three
      component mixtures. Clean separation of 13C NMR subspectra was achieved for three
      synthetic polymers mixed as powders. Applying the procedure to both 13C and 31P
      CP-MAS NMR spectra of solid dairy pond sludge provided clues to the location of
      the phosphorus relative to different types of organic matter, and provided
      estimates of the proportions of organic matter in categories labeled "plant
      fragments", "partly degraded residues" and "recalcitrant structures". The editing
      procedure increased noise levels by factors between 2 and 11 in these worked
      examples, depending on the degree of difficulty involved in distinguishing
      differences in proton spin relaxation time constants.

PMID- 7583063
TI  - Solid-state nuclear magnetic resonance investigations on chlorocyclophosphazenes.
AB  - The present study deals with solid-state nuclear magnetic resonance (NMR)
      investigations on hexachlorocyclotriphosphazene (N3P3Cl6) and T and K form of
      octachlorocyclotetraphosphazene (N4P4Cl8). Using 31P NMR we have recorded spectra
      of different magic-angle spinning (MAS) frequencies and static powder spectra. By
      means of the analysis of spinning sideband intensities the isotropic chemical
      shifts and the principal values of the chemical shift tensor could be determined.
      Because of the interactions between phosphorus and the neighbouring chlorine
      nuclei in the MAS spectra of N3P3Cl6 and N4P4Cl8 more lines were found to exist
      than was expected with regard to the isotropic chemical shift values according to
      the crystallographic phosphorus positions. To support this evidence solid-state
      spectra of the geminally disubstituted compound 2,2,4,4-tetrachloro-6,6
      bisthiophenylcyclotriphosphazene [N3P3Cl4(SPh)2] were used. In addition, by means
      of the individual gauched localized orbitals (IGLO) method 31P NMR chemical
      shifts, principal values and the orientation of the principal axes of the
      shielding tensor were calculated for the chlorocyclophosphazenes.

PMID- 7583064
TI  - 1H solid-state nuclear magnetic resonance study of the mobility of the
      tetrapropylammonium template in a purely siliceous MFI-type zeolite.
AB  - Dynamics of tetrapropylammonium (TPA) cation occluded during the synthesis in a
      siliceous MFI zeolite is investigated by 1H broad-line nuclear magnetic resonance
      (NMR) methods. Second moments M2, spin-lattice relaxation times T1 and T1 rho are
      measured in a large temperature domain. To al comparison, similar measurements
      are also reported in bulk tetrapropylammonium bromide (TPABr). Whereas methyl
      reorientation at low temperature and tumbling of the cation in the plastic phase
      are observed in crystalline TPABr in accordance with published studies, a new
      slower motion which could not be identified is observed below the phase
      transition. Such a motion is much more clearly shown by the existence of a
      minimum of T1 rho in a quenched sample. Our measurements in the zeolite
      demonstrate that the TPA template exhibits a larger and more complex mobility
      below 378 K. Beyond the fast methyl reorientation, the results disclose a motion
      which probably involves the entire propyl arms inside the channels. So the
      zeolite framework seems to make such a kind of motion easier. On the contrary,
      even at 450 K, the highest temperature investigated, the tumbling which would
      necessitate exchange of the propyl arms between the channels is not observed. A
      slow motion, responsible for a decrease of T1 rho above 350 K, could not be
      identified. While a simple correlation time is sufficient to describe the
      relaxation time dependences in TPABr, a distribution (such as Williams-Watts) is
      required to account for those in the zeolite.

PMID- 7583065
TI  - Set-up samples for 199Hg cross-polarization magic-angle spinning nuclear magnetic
      resonance spectroscopy.

PMID- 7583066
TI  - Pulsed-gradient spin-echo measurements of anisotropic diffusion by dipole
      decoupled 13C nuclear magnetic resonance.
AB  - A new approach for monitoring diffusion in anisotropic phases is proposed and
      demonstrated. The method relies on the observation of dilute spins (e.g., 13C) in
      the presence of heteronuclear high-power dipolar decoupling, a procedure which
      can yield time-domain nuclear magnetic resonance (NMR) signals lasting over three
      orders of magnitude longer than their 1H counterparts. This allows one to apply
      conventional 90-180 degrees pulsed-gradient spin-echo (PGSE) schemes on organic
      systems without having to employ complex and highly sensitive multiple-pulse 1H
      irradiation schemes. Instrumental aspects of this 13C method are discussed, and
      an application to the variable-temperature determination of anisotropic self
      diffusion in a thermotropic liquid crystal is illustrated.

PMID- 7583068
TI  - 17O magic-angle spinning nuclear magnetic resonance of CaCO3.
AB  - The first 17O magic-angle spinning nuclear magnetic resonance (MAS-NMR) from a
      carbonate ion in an inorganic compound is reported. The 17O MAS centreband of
      CaCO3 can be simulated with parameters CQ = 6.97 MHz, eta approximately 1 and an
      isotropic chemical shift of 204 ppm.

PMID- 7583067
TI  - Measurements of spin-lattice relaxation times, T1, in Na2O-MgO-SiO2 glasses doped
      with MnO.
AB  - Silicate glasses without paramagnetic components show 29Si relaxation times, T1,
      in the order of minutes. Because of these T1 values, unacceptably long instrument
      times are needed to obtain satisfactory' signal-to-noise ratios. Therefore, all
      samples were doped with MnO when microstructures of electrode glasses were
      investigated. Small amounts of paramagnetic ions in the glass reduce the
      relaxation time but do not affect the electrode properties. In any case when the
      distribution of manganese ions is homogeneous, the relaxation rates are
      proportional to the MnO content. The spin-lattice relaxation times of the
      different Qn species are similar within error limits. The best spectra were
      obtained using 0.1 mol% MnO.

PMID- 7583069
TI  - On the pictorial representation of the magnetic screening tensor: ellipsoid or
      ovaloid?
AB  - The pictorial representation of the magnetic screening tensor as ellipsoid (half
      axes root 1/sigma ii) is inconvenient. Much more obvious is an ovaloid with half
      axes sigma ii. The shape of this ovaloid is described in the dependence on the
      diagonal elements sigma 11, sigma 22 and sigma 33 of the principal axes of the
      screening tensor.

PMID- 7583070
TI  - Nuclear magnetic resonance proton dynamics study of [N(CH3)2H2]3Bi2I9 at low
      temperature.
AB  - The phase transitions of dimethylammonium nonaiododibismuthate [N(CH3)2H2]3Bi2I9
      were studied by investigating the temperature dependence of the line widths and
      proton spin-lattice relaxation times in the nuclear magnetic resonance spectrum.
      Two phase transitions appeared to be connected with motions of the cationic and
      CH3 group in the molecule, while the third one seemed to be connected with the
      dynamics of the Bi2I9 group.

PMID- 7583072
TI  - From basic advances to therapeutic strategies in ulcerative colitis.

PMID- 7583071
TI  - Proton dynamics in solid noradrenaline hydrochloride.
AB  - The temperature dependencies of the proton spin-lattice relaxation times and
      second moment of the 1H nuclear magnetic resonance line have been measured for
      noradrenaline hydrochloride. Two symmetric minima of T1 are observed. They can be
      explained in terms of reorientation of the ammonium groups and proton transfer in
      the hydrogen bond. The activation parameters have been determined.

PMID- 7583073
TI  - Pruritus of chronic cholestasis.
AB  - Pruritus is a challenging clinical problem which often complicates chronic
      cholestatic liver disease. For practical purposes, cholestasis may be defined as
      impaired hepatocellular secretion of bile and is a feature of a wide variety of
      liver diseases. Cholestasis is usually suspected clinically when a patient
      presenting with jaundice or pruritus is found to have an elevation in serum
      alkaline phosphatase activity disproportionate to increases in serum
      aminotransferase levels. Early imaging by ultrasonography, computerized
      tomography, or cholangiography is important to address the possibility of
      remediable biliary tract obstruction. The majority of patients who develop
      problematic pruritus due to chronic cholestasis will have one of several
      diseases: primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced
      cholestasis, autoimmune chronic active hepatitis, or alcoholic liver disease.
      Specific aetiological diagnosis is usually possible when history and physical
      examination are complemented, as appropriate, by serological testing,
      hepatobiliary imaging, and liver biopsy. This review does not address issues in
      diagnosis, but concentrates upon the management of pruritus, a potentially
      disabling complication of prolonged cholestasis.

PMID- 7583074
TI  - Long-term treatment of Wilson's disease with triethylene tetramine
      dihydrochloride (trientine).
AB  - Long-term treatment with triethylene tetramine dihydrochloride, (trientine, TETA)
      was evaluated in 19 patients with Wilson's disease (WD). Two were given the drug
      as first choice and 17 after treatment with penicillamine. The change was made
      because of side-effects, lack of improvement or worsening of neurological
      symptoms. All penicillamine-induced side-effects reverted. Thirteen patients
      still receive trientine, and the mean total observation time on this treatment is
      8.5 years/patient. Seven of the 13 are free from symptoms related to WD, five
      have mild to moderate neurological symptoms, mainly dysarthria. One patient with
      neurological symptoms who received trientine from the start of treatment
      deteriorated rapidly and is now severely dystonic. The symptoms initially
      worsened and later improved in one patient. All other patients improved during
      trientine treatment. Three patients died: two from a multifocal cancer including
      the liver and one non-complier from a ruptured spleen. Two patients underwent
      liver transplantation for progressive liver failure: one non-complier and one
      with liver cirrhosis whose liver function deteriorated despite treatment; both
      are now free from symptoms. Unexpectedly, two patients developed a serious
      colitis, one with duodenitis as well, that improved after withdrawal of the drug.
      No other unfavourable effects of trientine were recorded.

PMID- 7583075
TI  - Disseminated disease due to Mycobacterium avium complex in AIDS.
AB  - We retrospectively analysed 46 cases of disseminated infection with Mycobacterium
      avium complex (MAC) within a cohort of 702 HIV-infected patients in Edinburgh.
      Clinical features were compared with case-matched controls (AIDS cases without
      disseminated MAC), and survival and progression times were controlled for
      confounding variables that influence survival. Disseminated MAC was diagnosed
      antemortem in 18% of AIDS patients, and was the AIDS-defining diagnosis in 6% of
      all AIDS cases. Concomitant colonization of respiratory and gastrointestinal
      tracts was common (61% and 48%, respectively). In 58% of cases, CD4+ counts were
      < 10 cells/mm3 (median 6 cells/mm3). Weight loss, anaemia, leucopenia, and
      elevated liver transaminases and alkaline phosphatase were significantly more
      common among cases than controls. Therapy was given in 74%, and not tolerated in
      32%. Following AIDS diagnosis, disseminated MAC incidence was 14% at one year,
      25% at 2 years and 36% at 3 years. Median survival after disseminated MAC
      diagnosis was 6 months, with shorter survival in untreated cases. However,
      overall survival from AIDS diagnosis was not significantly different between
      patients who did or did not develop disseminated MAC. Disseminated MAC
      contributes significantly to AIDS morbidity, and its incidence increases with
      prolonged AIDS survival. Although survival following diagnosis is short, the
      development of disseminated MAC in AIDS probably does not affect overall
      survival. In cohorts with a low incidence, an alternative to prophylaxis might be
      surveillance and early diagnosis.

PMID- 7583076
TI  - HIV-associated renal disease in London hospitals.
AB  - We report experience from London hospitals which further illustrates the
      heterogeneous nature of HIV-associated nephropathy (HIVAN). Nineteen HIV-positive
      patients underwent renal biopsy from 1992 to 1994. Fourteen were male, five
      female. Eleven were Afro-Caribbean, 7 Caucasian and 1 Asian. Eleven patients had
      classical HIVAN with proteinuria, rapidly progressive renal failure and features
      of focal and segmental glomerulosclerosis (FSGS) on renal biopsy, and three of
      these had associated tubulo-interstitial nephritis (TIN). One further patient had
      TIN and tubular changes suggestive of HIVAN but no glomeruli were present in the
      biopsy. Other biopsy findings were of focal proliferative glomerulonephritis and
      TIN (1 patient), pauci-immune crescentic glomerulonephritis and TIN (1 patient),
      membranous nephropathy (1 patient), membranoproliferative nephropathy (1 patient)
      and haemolytic uraemic syndrome (2 patients). Of 11 patients with FSGS, seven
      died with median survival of 8 months (range 23 days-46 months) and five are
      still alive after median follow-up of 18 months (range 10-22 months). Of patients
      with glomerular disease other than FSGS, five died, with median survival of 3
      months (range 1-27 months) and two have survived (10 and 27 months,
      respectively). Thirteen patients had renal failure, 10 of whom had FSGS. In 10
      cases renal failure was acute and in two was the presenting feature of HIV
      infection. Thirteen patients underwent renal replacement therapy. Four received
      haemodialysis, and all died within one month. Nine patients received CAPD. Two
      were able to discontinue dialysis. Of the remaining seven, five died with median
      survival of 8 months (range 1.3-40 months) and two are alive 1 and 10 months
      after beginning dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583077
TI  - Decreased axial and peripheral bone density in patients taking long-term
      warfarin.
AB  - Impaired vitamin K metabolism is associated with under-carboxylation of the non
      collagenous bone-matrix protein osteocalcin, which is required in its fully
      carboxylated state for normal bone formation. Post-menopausal women have under
      carboxylation of osteocalcin which increases with age and is marked in the
      elderly. A similarly marked degree of impaired carboxylation occurs during
      coumarin therapy, and a key question is whether this may lead to accelerated loss
      of bone mass which is clinically important. We measured axial and peripheral bone
      mineral density (BMD) in 40 male patients on warfarin and 40 controls
      individually matched for age, disease and other drug therapy. A consistent trend
      for reduced BMD at all sites was observed in the warfarin-treated patients. This
      was particularly marked in the cancellous bone at the distal radius (9%
      reduction, p = 0.023) and at the cancellous rich lumbar spine site (10.4%
      reduction, p < 0.004). No significant relationship was observed between warfarin
      dose, International Normalized Ratio (INR) or duration of therapy and bone
      density. Because of the biochemical similarity, this study provides a new lead on
      post-menopausal osteoporosis, and supports the hypothesis that impaired
      carboxylation of osteocalcin plays a role in the pathogenesis of bone loss in the
      elderly through deficiency in vitamin K metabolism.

PMID- 7583078
TI  - Malignant hypertension in the elderly.
AB  - To investigate age-related differences in malignant hypertension (MHT), we
      studied 38 elderly patients (18 males, 20 females; mean age 70.6 years, SD 4.6
      years, range 65 to 84) and 277 younger patients (193 males, 84 females; mean age
      46.4 years, SD 10.5, range 15 to 64) with MHT presenting 1965-93. Mean duration
      of known hypertension before presentation was greater in the elderly group (43.8
      months vs. 23.1 months). The elderly group included 18 (47.4%) newly diagnosed
      hypertensives, compared to 160 (55.8%) in the younger group. At presentation, 19
      (50.0%) elderly patients were receiving no antihypertensive drug therapy, whilst
      18 (47.4%) were taking one or more drugs for hypertension. Presenting clinical
      features in elderly MHT patients included visual disturbance (9), headaches (2),
      headaches with visual disturbance (2), stroke (3), and heart failure (2). Six
      patients were asymptomatic. The commonest clinical complications were ischaemic
      heart disease (angina and myocardial infarction) (5), heart failure (4) and
      stroke (4). The majority (58%) of patients, however, had no vascular
      complications at presentation. Comparing elderly and younger MHT groups, there
      was no significant difference in presenting systolic blood pressures, although
      mean diastolic blood pressure was significantly greater in the younger group
      (mean 143.7 mmHg +/- 19.3 vs. 130.0 mmHg +/- 15.2; p < 0.0001). After a mean
      follow-up of 30.9 months (SD 37.1; range 1 to 123 months), 17 (44.7%) of the
      elderly patients were still alive, 15 were dead (39.5%) and six were lost to
      follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583079
TI  - In-patient workload in medical specialties: 1. Demographic profiles and time
      trends from linked statistics.
AB  - Admission rates, multiple admissions per individual and time spent in hospital in
      general medical and geriatric care are described using data from the Oxford
      Record Linkage Study from 1968-86. For patients aged 15-39 years, age-specific
      admission rates did not vary appreciably with age and were a little higher in
      women than in men. For patients aged 40 years and over, admission rates rose
      steeply with age and were considerably higher in men than in women. Admission
      rates, measured as episodes, increased over time by 3.4% per year in women and
      3.7% in men. Measured as individual people admitted per year, they increased by
      2.2% per year people in women and 2.6% in men. Expressed as age-standardized
      rates, they increased by 1.5% per year in women and 1.8% in men. The greater rise
      in episodes than in people treated reflected an increase in repeat admissions per
      patient admitted. Mean length of stay per hospital episode and total time spent
      in hospital per patient admitted per year both showed a consistent decline over
      time. Increases in admission rates were seen in all of the common broad clinical
      groupings studied, except infectious diseases which, as a group, showed a mean
      annual decrease of just over 2% per year.

PMID- 7583080
TI  - In-patient workload in medical specialties: 2. Profiles of individual diagnoses
      from linked statistics.
AB  - We analysed hospital use for 58 common clinical conditions in the medical
      specialties, using data from the two districts covered by the Oxford record
      linkage study 1968-1986. Episode rates, person rates, and ratios of multiple
      admissions per person were computed. In young adults, poisoning was the most
      common reason for admission. In older adults, the most common clinical conditions
      included atherosclerotic diseases and smoking-related lung diseases. Comparing
      the first and last time periods studied, admission rates increased by 10% or more
      in 37 of the 58 conditions, including 7 of the 10 conditions with the highest
      overall hospitalization rates. Conditions in which admissions increased by 10% or
      more included myocardial infarction, other ischaemic heart disease, chronic
      obstructive lung disease, asthma, pneumonia, diabetes, poisoning, dementia,
      prostate cancer and breast cancer among others. Workload declined by 10% or more
      in 13 conditions, including stroke, subarachnoid haemorrhage, hypertension,
      thyrotoxicosis, acquired hypothyroidism, and tuberculosis. Secular trends in
      hospital use are generally attributable either to changes in disease frequency in
      the population or to changes in clinic- or hospital-based technology and
      practice.

PMID- 7583081
TI  - Treating Alzheimer's disease.

PMID- 7583082
TI  - QT dispersion in essential hypertension.

PMID- 7583083
TI  - Exchange transfusion for falciparum malaria.

PMID- 7583084
TI  - The caduceus and the Aesculapian staff.

PMID- 7583085
TI  - Centromeric chromatin. Histone deviants.
AB  - Highly variant histones are targeted to specialized chromatin domains, such as
      the centromere where they have an essential role in the segregation of sister
      chromatids at mitosis.

PMID- 7583087
TI  - Evolutionary genetics. The silence of the genes.
AB  - A low mutation rate is required for the evolution of large genomes. But is the
      repression of inadvertent gene expression also important, and is the evolution of
      complexity limited by the efficiency of noise reduction?

PMID- 7583086
TI  - Molecular chaperones. Resurrection or destruction?
AB  - Recent studies implicate Hsp104/Clp family chaperones in both protein
      disaggregation and protein degradation. How do these homologous ring-shaped
      complexes function in such different ways?

PMID- 7583090
TI  - AIDS. Viruses, cytokines and Kaposi's sarcoma.
AB  - HIV infection strongly predisposes people to Kaposi's sarcoma, a complex
      proliferative lesion driven by autocrine and paracrine cytokine expression; new
      evidence implicates a second virus in the etiology of the disease.

PMID- 7583088
TI  - Haemoglobin engineering. For fun and money.
AB  - The recent transplantation of an unusual allosteric effect from crocodile to
      human haemoglobin has implications for both molecular evolution and the
      engineering of artificial blood substitutes.

PMID- 7583089
TI  - Photomorphogenesis. Seeing the light in plant development.
AB  - COP1, a protein thought to repress plant photomorphogenesis in the dark, is
      nuclear in the dark and cytoplasmic in the light. It may lie on the light signal
      transduction pathway and may be inactivated intracellularly by light.

PMID- 7583091
TI  - DNA replication. Once, and only once.
AB  - The preparation for DNA replication initiation is tightly linked to cell-cycle
      progression, ensuring that replication occurs only once per cycle. The time is
      ripe for a molecular dissection of the links between the two processes.

PMID- 7583092
TI  - Translational control. Awakening dormant mRNAs.
AB  - The translational control of many maternal mRNAs in oocytes and early embryos
      relies on changes in poly(A) tail length; the factors controlling poly(A) tail
      length are being identified in a range of species.

PMID- 7583093
TI  - Face recognition. What are faces for?
AB  - Recent studies suggest that the recognition of face identity and expression, and
      the interpretation of socially relevant information conveyed by faces, occur in
      distinct regions of the primate brain.

PMID- 7583095
TI  - Quantitative genetics. Loci with large effects.
AB  - Recent studies with the fruitfly Drosophila suggest that alleles of loci known
      from classical genetics can make major contributions to continuous-trait
      variation.

PMID- 7583094
TI  - Microtubule dynamics. Kinetochores get a grip.
AB  - Analysis of the interactions between purified motor proteins or isolated
      chromosomes and shrinking microtubules has shed light on the mechanism of
      chromosome segregation at mitosis.

PMID- 7583096
TI  - Structure prediction. How good are we?
AB  - Recent successes show that, in certain circumstances, protein secondary
      structures can be predicted with high accuracy. How far are we from being able to
      predict the complete structure of a protein from its sequence?

PMID- 7583097
TI  - Neural development. A 'LIM code' for motor neurons?
AB  - Combinatorial expression of LIM homeobox genes in subsets of embryonic motor
      neurons defines early stages in the topographic and functional organization of
      the spinal cord motor columns.

PMID- 7583098
TI  - Repair and recombination. How to make ends meet.
AB  - The repair of double-stranded breaks in DNA and the recombination of antibody
      gene V(D)J segments share a common pathway involving the Ku protein, which binds
      DNA ends, and its associated protein kinase.

PMID- 7583099
TI  - Functions of fibroblast growth factors and their receptors.
AB  - Fibroblast growth factors were first characterized twenty years ago as mitogens
      of cultured fibroblasts. Despite a wealth of data from experiments in vitro,
      insights have begun to emerge only recently on the normal function of these
      growth factors in mice and humans, as a result of studies of natural and
      experimental mutations in the factors and their receptors.

PMID- 7583100
TI  - A role for activator-mediated TFIIB recruitment in diverse aspects of
      transcriptional regulation.
AB  - BACKGROUND: Transcription by RNA polymerase II in eukaryotic cells requires the
      ordered assembly of general transcription factors on the promoter to form a
      preinitiation complex. Transcriptional activator proteins (activators) stimulate
      transcription by increasing the rate and/or extent of preinitiation complex
      assembly. We have shown previously that acidic activators increase the stable
      association of TFIIB on the promoter, a process we refer to as 'recruitment'. In
      this study, we provide evidence that diverse activators facilitate TFIIB assembly
      by a related mechanism. We then investigate the activator-mediated assembly of
      TFIIB with regard to two aspects of transcription: the distance-dependence of
      activator function, and reinitiation. RESULTS: We have previously described amino
      acid-substitution mutants of TFIIB that are able to support an activator
      independent basal level of transcription but do not respond to acidic activators.
      We now show that these mutants also do not respond to other classes of
      activators. We demonstrate that this defect is due to a failure of the activators
      to recruit the mutant TFIIB to the promoter. Activators often lose activity as
      their distance from the initiation site is increased. We show that this impaired
      transcriptional activity correlates with a decrease in TFIIB recruitment.
      Finally, we find that following the initiation of transcription, TFIIB
      dissociates from the promoter, requiring the activator-mediated reassembly of
      TFIIB in the preinitiation complex for each new round of transcription.
      CONCLUSION: We have provided evidence that diverse activators recruit TFIIB to
      the promoter by a related mechanism. This central step in transcriptional
      activation is sensitive to promoter architecture, and is required for each new
      round of transcription.

PMID- 7583101
TI  - The bacterial actin nucleator protein ActA of Listeria monocytogenes contains
      multiple binding sites for host microfilament proteins.
AB  - BACKGROUND: Several intracellular pathogens, including Listeria monocytogenes,
      use components of the host actin-based cytoskeleton for intracellular movement
      and for cell-to-cell spread. These bacterial systems provide relatively simple
      model systems with which to study actin-based motility. Genetic analysis of L.
      monocytogenes led to the identification of the 90 kD surface-bound ActA
      polypeptide as the sole bacterial factor required for the initiation of
      recruitment of host actin filaments. Numerous host actin-binding proteins have
      been localized within the actin-based cytoskeleton that surrounds Listeria once
      it is inside a mammalian cell, including alpha-actinin, fimbrin, filamin, villin,
      ezrin/radixin, profilin and the vasodilator-stimulated phosphoprotein, VASP. Only
      VASP is known to bind directly to ActA. We sought to determine which regions of
      the ActA molecule interact with VASP and other components of the host
      microfilament system. RESULTS: We used the previously developed mitochondrial
      targeting assay to determine regions of the ActA protein that are involved in the
      recruitment of the host actin-based cytoskeleton. By examining amino-terminally
      truncated ActA derivatives for their ability to recruit cytoskeletal proteins, an
      essential element for actin filament nucleation was identified between amino
      acids 128 and 151 of ActA. An ActA derivative from which the central proline-rich
      repeats were deleted retained its ability to recruit filamentous actin, albeit
      poorly, but was unable to bind VASP. CONCLUSIONS: Our studies reveal the initial
      interactions that take place between invading Listeria and host microfilament
      proteins. The listerial ActA polypeptide contains at least two essential sites
      that are required for efficient microfilament assembly: an amino-terminal 23
      amino-acid region for actin filament nucleation, and VASP-binding proline-rich
      repeats. Hence, ActA represents a prototype actin filament nucleator. We suggest
      that host cell analogues of ActA exist and are important components of structures
      involved in cell motility.

PMID- 7583102
TI  - Density-dependent regulation of cell growth by contactinhibin and the
      contactinhibin receptor.
AB  - BACKGROUND: The number of cells within mammalian tissues is maintained by growth
      stimulating and growth-inhibiting mechanisms, with inhibitory signals being
      superimposed over growth stimuli. This is reflected, in the culture of normal
      adherent cells, by the phenomenon of density-dependent inhibition of growth:
      cells cease proliferation after becoming a confluent monolayer. We have shown
      previously that a plasma membrane glycoprotein, contactinhibin, is a major
      effector of negative growth regulation. Although transformed cells express
      contactinhibin in a functionally active form, they are not growth-inhibited,
      suggesting that the defects that lead to their aberrant growth are located
      'downstream' of contactinhibin. RESULTS: Here, we provide evidence that a 92 kD
      plasma membrane protein, which we call CiR, binds specifically to contactinhibin
      and acts as a receptor mediating the contact-dependent inhibition of growth of
      cultured human fibroblasts. When polyclonal antibodies against CiR were
      introduced into cells using liposomes, confluent cells were released from density
      dependent growth control. By contrast, cross-linking CiR that is localized to the
      plasma membrane, using anti-CiR antibodies, led to growth inhibition, suggesting
      that CiR is a signalling molecule and implicating CiR oligomerization in signal
      generation. This conclusion is supported by the finding that binding of
      contactinhibin by CiR is strongly dependent on the local concentration of both
      molecules and has a sharp threshold. When CiR was isolated by immuno
      precipitation under conditions favouring phosphorylation, it was
      hyperphosphorylated on serine and threonine residues and had reduced
      contactinhibin-binding capacity; the binding capacity of CiR was restored after
      treatment with potato acid phosphatase. Fibroblasts transformed with simian virus
      40 had reduced CiR expression, higher CiR phosphorylation levels, and a strongly
      reduced capacity of CiR to bind to contactinhibin. Phosphatase treatment of the
      CiR isolated from transformed cells only partially restored its contactinhibin
      binding capacity. CONCLUSIONS: Homeostasis is the net result of a highly balanced
      network of growth-stimulating and growth-inhibitory signals. We have shown that
      density-dependent inhibition of growth in vitro is mediated by the interaction of
      contactinhibin with a 92 kD plasma membrane glycoprotein, CiR, the contactinhibin
      binding capacity of which is regulated by phosphorylation.

PMID- 7583103
TI  - Coincidence detection at the level of phospholipase C activation mediated by the
      m4 muscarinic acetylcholine receptor.
AB  - BACKGROUND: One of the principal mechanisms by which G-protein-coupled receptors
      evoke cellular responses is through the activation of phospholipase C (PLC) and
      the subsequent release of Ca2+ from intracellular stores. Receptors that couple
      to pertussis toxin (PTX)-insensitive G proteins typically evoke large increases
      in PLC activity and intracellular Ca2+ release. In contrast, receptors that use
      only PTX-sensitive G proteins usually generate weak PLC-dependent responses, but
      efficiently regulate a second effector enzyme, adenylyl cyclase. For example, in
      many cell types, agonist binding by the m4 muscarinic acetylcholine receptor (m4
      receptor) results in a strong inhibition of adenylyl cyclase and very little
      stimulation of PLC activity or release of intracellular Ca2+. We have
      investigated whether the weak, PTX-sensitive stimulation of PLC activity by the
      m4 receptor can play a significant role in the generation of cellular responses.
      RESULTS: We report here that PTX-sensitive Ca2+ release mediated by the m4
      receptor in transfected Chinese hamster ovary cells is greatly enhanced when
      endogenous purinergic receptors simultaneously activate a PTX-insensitive
      signaling pathway. Furthermore, m4-receptor-induced transcription of the c-fos
      gene (a Ca(2+)-sensitive response) is similarly potentiated when purinergic
      receptors are coactivated. These enhanced m4-receptor-dependent Ca2+ responses do
      not require an influx of external Ca2+, and occur in the absence of detectable
      purinergic-receptor-stimulated Ca2+ release; they apparently require the
      activation of both PTX-sensitive and PTX-insensitive G-protein pathways.
      Measurements of phosphoinositide hydrolysis indicate that the enhancement of m4
      receptor-mediated Ca2+ signaling by purinergic receptors is due to a synergistic
      increase in agonist-stimulated PLC activity. CONCLUSIONS: These studies
      demonstrate that the potency of m4-receptor-mediated PLC signaling is highly
      dependent upon the presence or absence of other PLC-activating agonists. The
      ability of the m4 receptor to evoke a strong, but conditional, activation of PLC
      may allow this type of receptor to participate in a coincidence-detection system
      that amplifies simultaneous PLC-activating signals through a mechanism involving
      crosstalk between PTX-sensitive and PTX-insensitive G-protein pathways.

PMID- 7583104
TI  - The McCollough effect reveals orientation discrimination in a case of cortical
      blindness.
AB  - BACKGROUND: The McCollough effect is a colour after-effect that is contingent on
      the orientation of the patterns used to induce it. To produce the effect, two
      differently oriented grating patterns--such as a red-and-black vertical grating
      and a green-and-black horizontal grating--are viewed alternatively for a few
      minutes. After this period of adaptation, if the black-and-white test gratings
      are viewed in the same orientation as the adaptation patterns, the white sections
      of the vertical grating will appear pale green and the white sections of the
      horizontal grating will appear pink. The McCollough effect indicates that colour-
      and orientation-coding mechanisms interact at some point during visual
      processing; but the question remains as to whether this interaction occurs at an
      early or later stage in the cortical visual pathways. In an attempt to answer
      this question, we studied a patient who had suffered extensive damage to
      extrastriate visual areas of the brain, which had left him able to see colour but
      little else. RESULTS: Neuropsychological and perceptual tests demonstrated that
      the patient, P.B., has a profound impairment in form perception and is even
      unable to discriminate between 90 degrees differences in the orientation of
      grating stimuli. He is also unable to use orientation information to control his
      reaching or grasping. Nevertheless, P.B. can name and discriminate different
      colours reliably, including those used to induce the McCollough effect. After
      adaptation with red-and-green gratings, P.B. appropriately reported the
      orientation-contingent aftereffect colours, even though he continued to be unable
      to discriminate the orientations of the test patterns. CONCLUSIONS: These results
      indicate that at some level in P.B.'s visual system orientation is being coded,
      but it is at a level that he is unable to use in making orientation judgements or
      in visuomotor control. Given the massive insult to the extrastriate cortex in
      P.B., it is likely that the anatomical locus of the mechanisms underlying the
      McCollough effect is within primary visual cortex or even earlier in the visual
      pathway.

PMID- 7583108
TI  - Colour vision. Adapting to change.
AB  - The colours we see reflect not only the light wavelengths presently being
      detected, but also those already received. To understand colour constancy
      therefore requires an understanding of adaptation in the visual system.

PMID- 7583107
TI  - DNA repair. Nucleotide excision-repair in the test tube.
AB  - The eukaryotic nucleotide excision-repair pathway has been reconstituted in
      vitro, an achievement that should hasten the full enzymological characterization
      of this highly complex DNA-repair pathway.

PMID- 7583106
TI  - Evolutionary immunology. A boost to immunity from nurse sharks.
AB  - A study of the nurse shark has revealed a type of rearranging gene that has yet
      to be seen in mammals; it encodes a secreted 'new antigen receptor' which, unlike
      shark immunoglobulin, revels in somatic hypermutation.

PMID- 7583105
TI  - Shape representation in the inferior temporal cortex of monkeys.
AB  - BACKGROUND: The inferior temporal cortex (IT) of the monkey has long been known
      to play an essential role in visual object recognition. Damage to this area
      results in severe deficits in perceptual learning and object recognition, without
      significantly affecting basic visual capacities. Consistent with these ablation
      studies is the discovery of IT neurons that respond to complex two-dimensional
      visual patterns, or objects such as faces or body parts. What is the role of
      these neurons in object recognition? Is such a complex configurational
      selectivity specific to biologically meaningful objects, or does it develop as a
      result of extensive exposure to any objects whose identification relies on subtle
      shape differences? If so, would IT neurons respond selectively to recently
      learned views of features of novel objects? The present study addresses this
      question by using combined psychophysical and electrophysiological experiments,
      in which monkeys learned to classify and recognize computer-generated three
      dimensional objects. RESULTS: A population of IT neurons was found that responded
      selectively to views of previously unfamiliar objects. The cells discharged
      maximally to one view of an object, and their response declined gradually as the
      object was rotated away from this preferred view. No selective responses were
      ever encountered for views that the animal systematically failed to recognize.
      Most neurons also exhibited orientation-dependent responses during view-plane
      rotations. Some neurons were found to be tuned around two views of the same
      object, and a very small number of cells responded in a view-invariant manner.
      For the five different objects that were used extensively during the training of
      the animals, and for which behavioral performance became view-independent,
      multiple cells were found that were tuned around different views of the same
      object. A number of view-selective units showed response invariance for changes
      in the size of the object or the position of its image within the parafovea.
      CONCLUSION: Our results suggest that IT neurons can develop a complex receptive
      field organization as a consequence of extensive training in the discrimination
      and recognition of objects. None of these objects had any prior meaning for the
      animal, nor did they resemble anything familiar in the monkey's environment.
      Simple geometric features did not appear to account for the neurons' selective
      responses. These findings support the idea that a population of neurons--each
      tuned to a different object aspect, and each showing a certain degree of
      invariance to image transformations--may, as an ensemble, encode at least some
      types of complex three-dimensional objects. In such a system, several neurons may
      be active for any given vantage point, with a single unit acting like a blurred
      template for a limited neighborhood of a single view.

PMID- 7583109
TI  - Bacterial pathogenesis. When a turn off is a turn on.
AB  - Pathogenic bacteria express distinct sets of genes at different stages in their
      life cycles; inappropriate expression of normally repressed genes during host
      colonization can interfere with bacterial survival.

PMID- 7583110
TI  - Intracellular regulation. Rac and Bcr regulate phagocytic phoxes.
AB  - The NADPH oxidase of phagocytes is essential for defence against invading
      microorganisms. The small GTpase Rac seems to be critical for the activation and
      deactivation of the phox proteins that make up this enzyme.

PMID- 7583111
TI  - Biodiversity. Managing nature when there are no 'ill winds'.
AB  - Interspecific interactions affect biodiversity, but in unpredictable ways that
      change over time and space. There is little evidence for the 'ill wind that blows
      no good' to any species. So how can we manage nature?

PMID- 7583112
TI  - Hearing. A gene for deaf ears?
AB  - Genetic mutations that lead to hearing losses have been identified in both human
      and mouse populations; the gene products include members of a class of
      unconventional myosins.

PMID- 7583114
TI  - Neurotrophic factors. Neurotrophin autocrine loops.
AB  - Developing neurons depend on neurotrophins supplied by the tissues they
      innervate. Before and after this period of target-dependent survival, brain
      derived neurotrophic factor also has autocrine actions on some neurons.

PMID- 7583113
TI  - Enzyme structures. DNA repair flips out.
AB  - New insights into the workings of the repair enzymes that police the genome for
      damage to DNA come from the recently determined structures of two uracil-DNA
      glycosylases.

PMID- 7583116
TI  - Steroid hormones. Membrane transporters of steroid hormones.
AB  - The discovery of a plasma membrane ABC protein that exports steroids in yeast
      highlights the possibility that similar membrane sorting systems in mammalian
      cells may modulate the access of steroids to their receptors.

PMID- 7583115
TI  - Intracellular signalling. Switching off signals.
AB  - In hematopoietic cells, the protein tyrosine phosphatase PTP1C appears to play a
      central role in the termination of signalling by receptors that activate protein
      tyrosine kinases.

PMID- 7583117
TI  - Lymphocyte migration. A new spin on lymphocyte homing.
AB  - New evidence confirms the multi-step model for leukocyte migration through
      endothelia, but with a twist. The selectins are not always required, and some
      lymphocyte subsets rely heavily on integrins for their migration to tissues.

PMID- 7583118
TI  - Cereal genome evolution. Grasses, line up and form a circle.
AB  - The genomes of six major grass species can be aligned by dissecting the
      individual chromosomes into segments and rearranging these linkage blocks into
      highly similar structures.

PMID- 7583119
TI  - Muscle development. Making Drosophila muscle.
AB  - Analysis of flies with mutations in the gene encoding the D-mef2 transcription
      factor identifies it as a controller of differentiation in multiple muscle cell
      types; it is the first such gene to be described.

PMID- 7583120
TI  - Inflammation. They're not just for clots anymore.
AB  - The identification of the blood-clotting inhibitor, protein S, as a ligand for a
      previously 'orphan' family of receptor tyrosine kinases demonstrates a new role
      for clotting and anti-clotting proteins in regulating cell proliferation.

PMID- 7583122
TI  - Targeting the mouse genome: a compendium of knockouts (Part II)

PMID- 7583121
TI  - Transcriptional control by protein phosphorylation: signal transmission from the
      cell surface to the nucleus.
AB  - Two general mechanisms have evolved for the rapid and accurate transmission of
      signals from cell-surface receptors to the nucleus, both involving protein
      phosphorylation. One mechanism depends on the regulated translocation of
      activated protein kinases from the cytoplasm to the nucleus, where they
      phosphorylate target transcription factors. In the second mechanism,
      transcription factors are kept in a latent state in the cytoplasm and are
      translocated into the nucleus upon activation.

PMID- 7583123
TI  - The first characterization of a eubacterial proteasome: the 20S complex of
      Rhodococcus.
AB  - BACKGROUND: The 26S proteasome is the central protease of the ubiquitin-dependent
      pathway of protein degradation. The proteolytic core of the complex is formed by
      the 20S proteasome, a cylinder-shaped particle that in archaebacteria contains
      two different subunits (alpha and beta) and in eukaryotes contains fourteen
      different subunits (seven of the alpha-type and seven of the beta-type). RESULTS:
      We have purified a 20S proteasome complex from the nocardioform actinomycete
      Rhodococcus sp. strain NI86/21. The complex has an apparent relative molecular
      mass of 690 kD, and efficiently degrades the chymotryptic substrate Suc-Leu-Leu
      Val-Tyr-AMC in the presence or absence of 0.05% SDS. Purified preparations reveal
      the existence of four subunits, two of the alpha-type and two of the beta-type,
      the genes for which we have cloned and sequenced. Electron micrographs show that
      the complex has the four-ringed, cylinder-shaped appearance typical of
      proteasomes. CONCLUSIONS: The recent description of the first eubacterial
      ubiquitin, and our discovery of a eubacterial proteasome show that the ubiquitin
      pathway of protein degradation is ancestral and common to all forms of life.

PMID- 7583125
TI  - Programmed cell death in the Drosophila central nervous system midline.
AB  - BACKGROUND: During the development of the central nervous system, large numbers
      of cells die by programmed cell death. This process requires the activity of
      specific gene products and subserves functions that include regulating the sizes
      of interacting cell populations and removing cells that provide transient
      functions. Resolution of programmed cell death often involves the elimination of
      dying cell corpses by phagocytic macrophages. In Drosophila, the reaper gene
      plays a crucial role in mediating programmed cell death; chromosomal deficiencies
      which remove reaper result in an absence of programmed cell death. We have used a
      reaper-deficiency mutant strain Df(3R)H99 (or H99), in conjunction with strains
      containing cell-type-specific markers, to examine the role of programmed cell
      death in differentiation of the embryonic central nervous system midline.
      RESULTS: Midline cell death was identified both by the presence of excess midline
      cells in H99 mutants and by the engulfment of dying midline cells by macrophages
      in wild-type embryos. These developmental deaths are lineage-specific: prominent
      midline glial death was observed, while little if any death was detected among
      the ventral unpaired median neurons. Examination of H99 mutants indicates that
      cell death is not required for the formation of macrophage precursors, or for
      their subsequent migration throughout the embryo; however, in the absence of
      dying cells, macrophage precursors do not exhibit morphological differentiation
      or phagocytosis. In both wild-type and H99 mutant embryos, a subset of
      macrophages migrate along the ventral midline. This midline migration is not
      observed in single-minded mutants, in which ventral midline cells fail to
      develop. CONCLUSIONS: Programmed cell death plays a crucial role in the
      development of the central nervous system midline, and dying midline cells are
      rapidly eliminated by phagocytic macrophages. It seems that the generation of
      engulfment signals in cells undergoing programmed cell death is downstream of
      reaper gene function, and that central nervous system midline and/or ventral
      epidermal cells provide directional cues for migrating macrophages.

PMID- 7583124
TI  - Phosphatidylinositol transfer protein dictates the rate of inositol trisphosphate
      production by promoting the synthesis of PIP2.
AB  - BACKGROUND: Phosphatidylinositol transfer protein (PI-TP), which has the ability
      to transfer phosphatidylinositol (PI) from one membrane compartment to another,
      is required in the inositol lipid signalling pathway through phospholipase C-beta
      (PLC-beta) that is regulated by GTP-binding protein(s) in response to
      extracellular signals. Here, we test the hypothesis that the principal role of PI
      TP is to couple sites of lipid hydrolysis to sites of synthesis, and so to
      replenish depleted substrate for PLC-beta. RESULTS: We have designed an
      experimental protocol that takes advantage of the different rates of release of
      endogenous PI-TP and PLC-beta from HL60 cells permeabilized with streptolysin O.
      We have examined the kinetics of stimulated inositol lipid hydrolysis in cells
      depleted of PI-TP, but not of endogenous PLC-beta, in the presence and absence of
      exogenous PI-TP. Linear time-courses were observed in the absence of any added
      protein, and the rate was accelerated by PI-TP using either guanosine 5'[gamma
      thio]-triphosphate (GTP gamma S) or the receptor-directed agonist fMetLeuPhe as
      activators. In addition, depletion from the cells of both PI-TP and PLC-beta
      isoforms by extended permeabilization (40 minutes) allowed us to control the
      levels of PLC-beta present in the cells. Once again, PI-TP increased the rates of
      reactions. To identify whether the role of PI-TP was to make available the
      substrate phosphatidylinositol bisphosphate (PIP2) for the PLC, we examined the
      synthesis of PIP2 in cells depleted of PI-TP. We found that PI-TP was essential
      for the synthesis of PIP2. CONCLUSIONS: The predicted function of PI-TP in
      inositol lipid signalling is the provision of substrate for PLC-beta from
      intracellular sites where PI is synthesized. We propose that PI-TP is in fact a
      co-factor in inositol lipid signalling and acts by interacting with the inositol
      lipid kinases. We hypothesize that the preferred substrate for PLC-beta is not
      the lipid that is resident in the membrane but that provided through PI-TP.

PMID- 7583126
TI  - Limb-patterning activity and restricted posterior localization of the amino
      terminal product of Sonic hedgehog cleavage.
AB  - BACKGROUND: Sonic hedgehog (Shh), a vertebrate homolog of the Drosophila segment
      polarity gene hedgehog (hh), has been implicated in patterning of the developing
      chick limb. Such a role is suggested by the restricted expression of Shh along
      the posterior limb bud margin, and by the observation that heterologous cells
      expressing Shh have limb-polarizing activity resembling that of cells from the
      polarizing region of the posterior limb bud margin. It has not been demonstrated,
      however, that the Sonic hedgehog protein (SHH) alone is sufficient for limb
      patterning. SHH has been shown to undergo autoproteolytic cleavage in vitro,
      yielding two smaller products. It is of interest, therefore, to determine whether
      processing of SHH occurs in the developing limb and how such processing
      influences the function of SHH. RESULTS: We demonstrate that SHH is
      proteolytically processed in developing chick limbs. Grafts of cells expressing
      SHH protein variants that correspond to individual cleavage products demonstrate
      that the ability to induce patterned gene expression and to impose morphological
      pattern upon the limb bud is limited to the amino-terminal product (SHH-N) of SHH
      proteolytic cleavage. We also demonstrate that bacterially synthesized and
      purified SHH-N, released from implanted beads, is sufficient for limb-patterning
      activity. Finally, we show that the endogenous amino-terminal cleavage product is
      tightly localized to the posterior margin of the limb bud. CONCLUSIONS: Our data
      show that, of the two cleavage products resulting from SHH autoproteolysis, SHH-N
      expressed in grafted heterologous cells or supplied in purified form is
      sufficient to impose pattern upon the developing limb. Moreover, the restricted
      localization of the endogenous amino-terminal SHH cleavage product to the
      posterior border of the chick limb bud makes it unlikely that its patterning
      activity results from it being distributed in a broad gradient across the antero
      posterior axis. More consistent with the observed localization is a model in
      which the amino-terminal SHH cleavage product exerts its patterning effects by
      local induction in or near the polarizing region, initiating a cascade of gene
      expression that ultimately extends across the developing limb.

PMID- 7583131
TI  - Light-harvesting complex. Rings of light.
AB  - The atomic structure of the bacterial light-harvesting complex helps to explain
      how the energy of sunlight is efficiently absorbed and transferred between
      bacteriochlorophyll molecules towards the reaction centre.

PMID- 7583130
TI  - Aging. Silence is golden.
AB  - A pioneering genetic analysis of aging in yeast has revealed that a protein
      complex known to play an essential role in transcriptional silencing at mating
      type loci and telomeres also controls aging and stress resistance.

PMID- 7583128
TI  - Tail bud determination in the vertebrate embryo.
AB  - BACKGROUND: Although as humans we lose our tails in the second month of embryonic
      development, a persistent tail is a prominent structural feature of most adult
      vertebrates. Indeed, the post-anal tail is part of the definition of a chordate.
      The internal organization of the developing tail--with neural tube, notochord and
      paired somites--is the same as that of the main body axis, so it can be expected
      that the mechanism of tail formation has a close relationship to that of the
      vertebrate body plan as a whole. Despite this, almost nothing is known about how
      tails arise. RESULTS: We present evidence to show that the tail bud of Xenopus
      laevis arises as the result of interactions between distinct zones of tissue at
      the posterior of the embryo at the neurula stage. These tissue interactions were
      demonstrated by manipulations of exogastrulae, which normally form no tail, and
      by transplantation experiments performed on the neural plate of stage 13
      neurulae, whereby embryos with supernumary tails were produced. CONCLUSIONS: We
      propose a new model of tail bud determination, termed the NMC model, to explain
      the results we have obtained. In this model, the tail bud is initiated by an
      interaction between two territories in the neural plate and a posterior
      mesodermal territory.

PMID- 7583129
TI  - Embryonic PCNA: a missing link?

PMID- 7583132
TI  - T-cell development. T-cell lineage commitment revisited.
AB  - Years of controversy about the lineage relationship between alpha beta and gamma
      delta T cells may at last have been resolved: it now appears that most T cells
      derive from an identical T-lineage committed precursor.

PMID- 7583133
TI  - Neural networks. Sleep and memory.
AB  - Recent experimental and theoretical advances suggest that memories may be
      reorganized in the cortex during sleep.

PMID- 7583134
TI  - Hybrid speciation. Evolution under the microscope.
AB  - Detailed genetic maps of three related sunflower species support the view that
      one species originated relatively recently from the other two by hybrid
      speciation, providing the first good evidence for this theory of speciation.

PMID- 7583127
TI  - A role for FGF-8 in the initiation and maintenance of vertebrate limb bud
      outgrowth.
AB  - BACKGROUND: The outgrowth of the vertebrate limb bud is the result of a
      reciprocal interaction between the mesenchyme and a specialized region of the
      ectoderm, the apical ectodermal ridge (AER), which overlies it. Signals emanating
      from the AER act to maintain the underlying mesenchyme, called the progress zone,
      in a highly proliferative and undifferentiated state. Removal of the AER results
      in the cessation of limb bud growth, thus causing limb truncation. The best
      candidates for this AER-derived signal are members of the fibroblast growth
      factor (FGF) family, in particular FGF-4, which can maintain limb bud outgrowth
      following removal of the AER. However, FGF-4 is only expressed after considerable
      outgrowth has occurred and a well-developed limb bud has formed, and then only in
      the posterior part of the AER. Likewise, the other FGFs studied to date are not
      candidates for this activity. RESULTS: We report evidence that a recently
      identified member of this family, FGF-8, is expressed in the ectoderm of the
      prospective limb territory prior to morphological outgrowth of the limb bud in
      both mouse and chick. Thereafter, expression is maintained throughout the AER
      during limb development. We have produced and purified the FGF-8 protein, and
      shown that it will substitute for the AER in maintaining limb bud outgrowth in
      mouse embryos from which the AER has been surgically removed. FGF-8 does not,
      however, maintain expression of the sonic hedgehog gene. CONCLUSIONS: These
      results indicate that FGF-8 is an AER-derived mitogen that stimulates limb bud
      outgrowth. Moreover, our data suggest that FGF-8 may also be an ectodermally
      derived mitogen that stimulates the onset of limb bud outgrowth (budding) in the
      absence of a morphological AER, and indicate the possible involvement of FGF-8 in
      the establishment of the limb field.

PMID- 7583135
TI  - Actin cytoskeleton. Missing link for intracellular bacterial motility?
AB  - Vasodilator-stimulated phosphoprotein (VASP) associates with virulence factors on
      the surface of intracellular bacteria; by binding to profilin, VASP may help
      direct the actin assembly that appears to drive bacterial motility.

PMID- 7583137
TI  - Limb evolution. Fish fins or tetrapod limbs--a simple twist of fate?
AB  - Comparisons between Hox gene expression patterns in teleost fins and tetrapod
      limbs are revealing new insights into the developmental mechanisms underlying the
      evolutionary transition from fin to limb.

PMID- 7583136
TI  - Neurotransmitters. NMDA receptors: do glia hold the key?
AB  - NMDA receptor stimulation requires binding of a 'co-agonist' and the
      neurotransmitter glutamate at separate sites. Are ligands for the co-agonist site
      liberated by glia, following activation of glial glutamate receptors?

PMID- 7583139
TI  - Memory mechanisms. Photographic memory in flies.
AB  - A new study of olfactory memory formation in Drosophila shows that a delicate
      balance of CREB transcription factor activity may play a decisive role in
      triggering long-term memory.

PMID- 7583140
TI  - Proteolysis. The proteasome: a protein-degrading organelle?
AB  - The crystal structure of the proteasome suggests that degradation of ubiquitin
      protein conjugates is achieved by unfolding the protein substrate and
      translocating it through a channel into a peptidase-containing chamber.

PMID- 7583141
TI  - Transcriptional regulation. Flipping the Myc switch.
AB  - When certain cells differentiate, Myc in Myc-Max heterodimers is replaced by Mad
      or Mxi, generating heterodimers that suppress transcription by interacting with
      the repressor Sin3.

PMID- 7583138
TI  - T-cell subsets. Who does the polarizing?
AB  - T cells can 'polarize' into T1 and T2 effector cell types in response to distinct
      cytokines. T cells and cells presenting antigen to the T cells are themselves
      candidate sources of these polarizing cytokines.

PMID- 7583143
TI  - T-cell activation. Two for T.
AB  - T-cell activation requires costimulation in addition to the antigen-specific
      signal. Recent results suggest that distinct costimulatory molecules can
      specifically activate different types of T-cell response.

PMID- 7583142
TI  - RNA processing. Wilms' tumour--the splicing connection?
AB  - Major isoforms of WT1--products of the tumour suppressor gene WT1, implicated in
      predisposition to Wilms' tumour--may preferentially interact with splicing
      factors, suggesting a role for WT1 in RNA processing.

PMID- 7583144
TI  - Photosynthesis. Regulation by redox signalling.
AB  - Photosynthesis is light-driven redox chemistry. Molecular redox signalling, the
      coupling of gene expression to electron transfer, is now implicated in the
      adaptation of photosynthesis to variation in light quality and quantity.

PMID- 7583145
TI  - Targeting the mouse genome: a compendium of knockouts (Part III)

PMID- 7583147
TI  - Involvement of MAP kinase in insulin signalling revealed by non-invasive imaging
      of luciferase gene expression in single living cells.
AB  - BACKGROUND: Studies of the mechanisms by which signals are transmitted from
      receptor tyrosine kinases would be facilitated by a way of monitoring events at
      the single-cell level. We have explored how luciferase imaging can be used to
      examine the role of specific signalling pathways in insulin-stimulated gene
      expression. The analysis of luciferase expression in single cells has previously
      been hampered by the insensitivity of existing methodologies and the lack of a
      way of monitoring quantitatively, and independently, more than one promoter
      within the same cell. We have developed a technique for examining the dynamics of
      insulin-stimulated AP-1-dependent transcription in single living cells, and have
      explored the signalling pathway involved. RESULTS: Luciferase and aequorin gene
      expression were examined in single living cells with a high-sensitivity photon
      counting camera. The technique involved the comicroinjection of luciferase- and
      aequorin-based reporter plasmids directly into the cell nucleus, and the
      subsequent analysis of luminescence in the presence of luciferin and
      coelenterazine, respectively. The method is quantitative and allows insulin
      stimulated gene expression to be monitored in real time. We found that insulin
      promoted a substantial increase in the expression of a luciferase gene under the
      control of the AP-1-binding site from the collagenase gene promoter. Aequorin
      expression, under the control of a cytomegalovirus promoter, was unaffected by
      insulin. The effect of insulin on luciferase expression was specifically blocked
      by overexpression of either the mitogen-activated protein (MAP) kinase
      phosphatase CL100, or the dominant-negative mutant MAP kinase kinase,
      MEKS217/221A. CONCLUSIONS: Microinjection coupled with luciferase imaging allows
      hormone-regulated gene expression from relatively weak promoters to be monitored
      in single living cells. We have used this method to demonstrate that MAP kinase
      plays a central role in the ability of insulin to stimulate AP-1-dependent gene
      transcription.

PMID- 7583146
TI  - Only one of the two DNA-bound orientations of AP-1 found in solution cooperates
      with NFATp.
AB  - BACKGROUND: The transcription factor AP-1 activates the expression of numerous
      genes in response to mitogenic stimuli. AP-1 regulates gene expression both
      through solitary binding to independent recognition sites and, in cooperation
      with various heterologous transcription factors, through targeting to composite
      response elements. The two subunits that make up the AP-1 heterodimer, Fos and
      Jun, possess identical residues at positions that make sequence-specific contacts
      to DNA. This degeneracy leaves the protein with no apparent way of orienting
      itself uniquely on DNA by differentially recognizing its two non-identical half
      sites. Here, we have analyzed the orientation of the AP-1 basic-leucine-zipper
      (bZip) domain on a cognate site, both alone and in the cooperative complex formed
      together with the 'nuclear factor of activated T cells' (NFATp). RESULTS: The
      results of affinity cleaving experiments demonstrate that, in solution, the AP-1
      bZip binds DNA as a mixture of two orientational isomers. However, in the
      cooperative complex formed with NFATp on a composite response element, the AP-1
      bZip adopts a single orientation, with Jun and Fos bound to the NFATp-proximal
      and NFATp-distal half-sites, respectively. Protein cross-linking experiments
      demonstrate that protein-protein contacts are responsible for this 'orientational
      locking'. CONCLUSIONS: Our results demonstrate that, through protein-protein
      interactions, one protein can force another to adopt a single DNA-bound
      orientation. Thus, cooperative interactions between adjacent regulatory proteins
      can influence not only the energetics of their interactions with DNA, but also
      their precise geometric and stereochemical arrangement. Because orientational
      isomers present markedly different structures to the transcriptional apparatus,
      it seems likely that orientation will exert an effect on the ability to activate
      transcription.

PMID- 7583148
TI  - How does taxol stabilize microtubules?
AB  - BACKGROUND: The antimitotic agent taxol is an important new drug for the
      treatment of certain cancers. It blocks the cell cycle in its G1 or M phases by
      stabilizing the microtubule cytoskeleton against depolymerization. RESULTS: We
      have used electron cryomicroscopy and image analysis to investigate the structure
      of microtubules assembled in vitro, and found that their fine structure was
      sensitive to the presence of taxol. The conformation of the microtubule lattice
      depended on whether the drug was added before or after assembly. The structure of
      preassembled microtubules changed only slightly when taxol was added; a larger
      change was observed when microtubules were assembled in the presence of the drug.
      In both cases, taxol-containing microtubules were stable over many days at, or
      below, room temperature. CONCLUSIONS: As in another recent investigation using
      guanylyl-(alpha,beta)-methylene-diphosphonate (a non-hydrolyzable GTP analogue),
      microtubule stabilization with taxol is accompanied by a conformational change in
      the microtubule surface lattice and, implicitly, in the tubulin dimer. We
      speculate that a general mechanism may underlie the stabilization of microtubules
      by different agents.

PMID- 7583149
TI  - Analysis of gene expression in a complex differentiation hierarchy by global
      amplification of cDNA from single cells.
AB  - BACKGROUND: Many differentiating tissues contain progenitor cells that differ in
      their commitment states but cannot be readily distinguished or segregated.
      Molecular analysis is therefore restricted to mixed populations or cell lines
      which may also be heterogeneous, and the critical differences in gene expression
      that might determine divergent development are obscured. In this study, we
      combined global amplification of mRNA transcripts in single cells with
      identification of the developmental potential of processed cells on the basis of
      the fates of their sibling cells from clonal starts. RESULTS: We analyzed clones
      of from four to eight hemopoietic precursor cells which had a variety of
      differentiative potentials; sibling cells generally each formed clones of
      identical composition in secondary culture. Globally amplified cDNA was prepared
      from individual precursors whose developmental potential was identified by
      tracking sibling fates. Further cDNA samples were prepared from terminally
      maturing, homogeneous hemopoietic cell populations. Together, the samples
      represented 16 positions in the hemopoietic developmental hierarchy. Expression
      patterns in the sample set were determined for 29 genes known to be involved in
      hemopoietic cell growth, differentiation or function. The cDNAs from a bipotent
      erythroid/megakaryocyte precursor and a bipotent neutrophil/macrophage precursor
      were subtractively hybridized, yielding numerous differentially expressed cDNA
      clones. Hybridization of such clones to the entire precursor sample set
      identified transcripts with consistent patterns of differential expression in the
      precursor hierarchy. CONCLUSIONS: Tracking of sibling fates reliably identifies
      the differentiative potential of a single cell taken for PCR analysis, and
      demonstrates the existence of a variety of distinct and stable states of
      differentiative commitment. Global amplification of cDNA from single precursor
      cells, identified by sibling fates, yields a true representation of lineage- and
      stage-specific gene expression, as confirmed by hybridization to a broad panel of
      probes. The results provide the first expression mapping of these genes that
      distinguishes between progenitors in different commitment states, generate new
      insights and predictions relevant to mechanism, and introduce a powerful set of
      tools for unravelling the genetic basis of lineage divergence.

PMID- 7583150
TI  - LMP2+ proteasomes are required for the presentation of specific antigens to
      cytotoxic T lymphocytes.
AB  - BACKGROUND: Major histocompatibility complex (MHC) class I molecules present
      short peptides generated by intracellular protein degradation to cytotoxic T
      lymphocytes (CTL). The multisubunit, non-lysosomal proteinases known as
      proteasomes have been implicated in the generation of these peptides. Two
      interferon-gamma (IFN-gamma)-inducible proteasome subunits, LMP2 and LMP7, are
      encoded within the MHC gene cluster in a region associated with antigen
      presentation. The incorporation of these LMP subunits into proteasomes may alter
      their activity so as to favour the generation of peptides able to bind to MHC
      class I molecules. It has been difficult, however, to demonstrate a specific
      requirement for LMP2 or LMP7 in the presentation of peptide epitopes to CTL.
      RESULTS: We describe a T-cell lymphoma, termed SP3, that displays a novel
      selective defect in MHC class I-restricted presentation of influenza virus
      antigens. Of the MHC-encoded genes implicated in the class I pathway, only LMP2
      is underexpressed in SP3 cells. Expression of IFN-gamma in transfected SP3 cells
      simultaneously restores LMP2 expression and antigen presentation to CTL.
      Expression of antisense-LMP2 mRNA in these IFN-gamma-transfected cells
      selectively represses antigen recognition and the induction of surface class I
      MHC expression. Moreover, the expression of this antisense-LMP2 mRNA in L929
      fibroblast cells, which constitutively express LMP2 and have no presentation
      defect, blocks the presentation of the same influenza virus antigens that SP3
      cells are defective in presenting. CONCLUSIONS: Our results show that the LMP2
      proteasome subunit can directly influence both MHC class I-restricted antigen
      presentation and class I surface expression.

PMID- 7583151
TI  - High-frequency developmental abnormalities in p53-deficient mice.
AB  - BACKGROUND: Several strains of mice carrying null mutations of the tumour
      suppressor gene p53 have been developed. It has been reported that homozygous
      mice from all of these strains develop normally to birth, but then succumb
      rapidly to neoplasia. RESULTS: Here, we report that a significant proportion of
      female p53-/- mice die during embryogenesis or in the period between birth and
      weaning, being subject to a spectrum of abnormalities. In a significant
      proportion (23%) of p53-/- female embryos, the normal process of neural tube
      closure failed, leading to exencephaly and subsequent anencephaly. Although this
      phenomenon was predominantly associated with females, we observed one affected
      male embryo. In addition to a spectrum of neural tube defects, many of these
      embryos exhibited a range of craniofacial malformations, including ocular
      abnormalities and defects in upper incisor tooth formation. We observed a
      significant reduction in the number of p53-/- female progeny of p53+/- x p53+/-
      matings, and also in an in utero analysis of the p53+/- female progeny of p53-/-
      x p53+/+ matings. When male mice were exposed to irradiation prior to mating, a
      significant increase in the rate of abnormality was seen in the progeny, which
      was specifically associated with p53 deficiency. CONCLUSIONS: We have identified
      a high rate of developmental abnormalities associated with p53 deficiency. This
      manifests itself as a spectrum of lesions, predominantly female-associated
      defects in neural tube closure. These defects may arise either because p53 plays
      a physiological role at the time of neural tube closure, or because of an
      abnormally high frequency of mutation within the haploid gametes of p53-null
      parents.

PMID- 7583152
TI  - Spiral and concentric waves organize multicellular Dictyostelium mounds.
AB  - BACKGROUND: It has been known for more than 20 years that the early aggregation
      of the slime mould Dictyostelium is driven by periodic waves of cAMP, which
      instruct the cells to collect at the aggregation centre. Although it has been
      hypothesized that cAMP waves are also involved in the organization of
      multicellular morphogenesis, wave propagation in the later stages of
      Dictyostelium development has not previously been demonstrated. RESULTS: We have
      developed special optical and digital-image-processing techniques that allow
      propagating waves of chemotactic activity to be visualized in multicellular
      aggregates. Using this technology, we have observed signal propagation in the
      multicellular, 'mound' stage of Dictyostelium discoideum. Within mounds, these
      waves were propagated as concentric rings, single armed spirals or multi-armed
      spirals. The spontaneous appearance of the latter structures was new and
      unexpected. The geometry of wave propagation was strain specific: strain XP55
      predominantly showed concentric ring waves, whereas spiral waves were typical of
      a derivative of XP55, streamer F mutant NP377, and of the widely used axenic
      strain AX-3. The different geometry of the signals was reflected by distinct cell
      movement patterns and different cell-movement speeds--cells in AX-3 mounds,
      organized by spiral waves, moved faster than cells in XP55 mounds, and spiral
      waves were always accompanied by rotational cell movement, whereas cells in XP55
      mounds moved towards the aggregation centre. CONCLUSIONS: The same principles-
      wave propagation and chemotaxis--that control Dictyostelium aggregation also
      govern the morphogenesis of the mound stage. Mounds behave as a highly excitable
      system in which a diverse range of signal-propagation geometries create the same
      biological structure--a migrating slug.

PMID- 7583154
TI  - PKC2 gene enquiry.

PMID- 7583155
TI  - Loose ends. Molecular biology by numbers ..... one.

PMID- 7583153
TI  - Patterning activities of vertebrate hedgehog proteins in the developing eye and
      brain.
AB  - BACKGROUND: The hedgehog (hh) family of secreted signaling proteins is
      responsible for developmental patterning in a variety of systems, including the
      neural tube, limbs and somites. Within the neural tube, at the level of the
      spinal cord, products of the vertebrate gene sonic hedgehog (shh) are proposed to
      function as a ventral patterning influence, with the capability of inducing floor
      plate and motor neurons. RESULTS: We report the isolation of tiggy-winkle
      hedgehog (twhh), a novel member of the zebrafish hh gene family. Both twhh and
      shh are expressed in the ventral midline of the embryonic zebrafish neural tube
      and brain, but twhh expression becomes limited to the neural tube, whereas shh is
      also expressed in the notochord. Both genes are expressed in the developing
      brain, in domains that include a discrete region in the floor of the
      diencephalon, located between the sites of the future optic stalks. Using pax-2
      and pax-6 as markers of proximo-distal fate within the developing eye, we found
      that ectopic expression of either hh gene promoted proximal fates and suppressed
      distal fates. In contrast, proximal fates were lost in cyclops mutant embryos,
      which lack twhh- and shh-expressing forebrain cells. Both twhh and shh proteins
      undergo autoproteolytic processing in vivo; a fragment corresponding to the amino
      terminal cleavage product was sufficient to carry out all signaling activities
      associated with twhh in eye and brain development. CONCLUSIONS: These findings
      suggest that secreted signals encoded by members of the hedgehog gene family,
      emanating from the ventral midline of the neural tube, not only play important
      roles in dorso-ventral patterning of the brain but also appear to constitute an
      early patterning activity along the proximo-distal axis of the developing eyes.

PMID- 7583156
TI  - Molecular biology in the intensive care unit: a framework for interpretation.
AB  - The tools of cellular and molecular biology provide insight into the mechanisms
      operating in cellular functions and have already advanced the diagnosis and
      treatment of human disease. The goal of this article is to provide a framework
      utilizing recent advances in basic science. Changing the frame of analysis from
      clinically familiar systems physiology to the interior of a cell, and then
      considering the cell as an information repository and processor, may simplify the
      interpretation of molecular and cellular studies. Gene therapy and manipulation
      of signal transduction pathways are used to demonstrate how the framework can be
      applied to augment clinicians' understanding of these processes.

PMID- 7583157
TI  - Introduction to modern molecular biology: fundamental concepts and techniques.
AB  - Over the past 15 years, knowledge of the molecular pathophysiology of human
      disease has increased at a remarkable pace. Most of this progress can be
      attributed to concomitant advances in basic molecular biology and, specifically,
      the development of an ever-expanding aramentarium of technologies for analysis of
      gene structure and function referred to as recombinant DNA technology. In this
      article, we provide an introduction to this technology by describing the basic
      language, principles, and tools of molecular biology as well as a few of the most
      widely used recombinant DNA techniques. By necessity, this discussion does not
      encompass the huge body of available molecular methodologies, but the information
      provided here should provide a sufficient framework for appreciating how
      recombinant DNA has already impacted, and how it will most certainly reshape, the
      practice of medicine.

PMID- 7583158
TI  - The use of molecular biology techniques for diagnostic microbiology and hospital
      epidemiology.
AB  - Clinical microbiologists and hospital epidemiologists have traditionally been
      concerned with the isolation and identification of organisms for diagnosis in
      individual patients, and the detection of transmission of such organisms from
      patient to patient. The use of molecular biology techniques, such as nucleic acid
      probing and amplification, provides the potential for revolutionizing how we
      diagnose infecting pathogens and determining the relation between nosocomial
      isolates. In clinical microbiology, this means that we will be able to detect
      smaller amounts of DNA or RNA of pathogens than is currently possible, that the
      time required to identify and determine the antimicrobial susceptibility of slow
      growing pathogens will be dramatically reduced, and that the diagnosis of
      nonculturable organisms will become possible. In hospital epidemiology, the use
      of such techniques has already provided tests with exceptional discriminatory
      power. Molecular techniques allow more efficient typing of all pathogens, and
      permit discrimination between strains of organisms that were previously
      phenotypically identical or uncharacterizable. Currently, cost and complexity
      limit the applicability of these techniques; however, they are likely to be
      developed for routine laboratory use in the next decade, and their impact will be
      considerable.

PMID- 7583159
TI  - The oxidative stress response.
AB  - Oxidative stress resulting from toxic effects of reactive oxygen species (ROS)
      plays an important role in the pathogenesis of a variety of diseases and
      important biological processes. Toxic effects of these ROS, including the
      superoxide and hydroxyl radicals, and hydrogen peroxide can cause cellular damage
      by oxidizing nucleic acids, proteins, and membrane lipids. While the chemical
      reactions involved in the generation and detoxification of ROS have been studied
      in great detail, little is known about the cellular and molecular responses to
      oxidative stress in mammalian cells. This article discusses some of the major
      aspects of these molecular responses, including alterations in the gene
      expression of antioxidant enzymes, stress-response genes, and cytokines. The
      regulatory mechanisms that control this genetic response are highly complex,
      involving activation of transcription factors and signal transduction pathways.
      Further characterization of the mechanisms that regulate these molecular
      responses is essential for understanding the physiologic function of the
      responses and for the development of new therapeutic modalities to defend and/or
      adapt to oxidant injury.

PMID- 7583160
TI  - The acute-phase response.
AB  - Inflammation and tissue injury elicit profound changes in the concentrations of
      several plasma proteins. These proteins are predominantly synthesized in the
      liver and named acute-phase proteins. The regulatory mechanisms that control this
      response are highly complex and include the release of various mediators
      affecting specific subsets of acute-phase genes. Individual mediators can either
      synergistically enhance or inhibit the effects of other mediators. Binding of
      mediators to their respective receptors on hepatocytes and transduction of this
      signal induce changes in acute-phase protein gene expression that are primarily
      regulated on a transcriptional level. However, under certain conditions post
      transcriptional mechanisms may also be involved in this process. Although some
      acute-phase proteins have been shown to minimize tissue damage, as well as to
      participate in hemostasis, tissue repair, and regeneration in response to injury,
      the actual in vivo functions of several acute-phase reactants remain speculative.
      Measurements of acute-phase protein plasma concentrations can be of diagnostic or
      prognostic value under certain clinical conditions. Further characterization of
      the regulatory mechanisms that govern the acute-phase response in vivo could lead
      to the development of new therapeutic strategies aimed at improving the
      organism's integrated response to injury.

PMID- 7583161
TI  - The heat-shock response.
AB  - Heat-shock proteins (HSPs) are a family of gene products that are expressed in
      response to stress in every living cell. This name was derived from early
      observations demonstrating their synthesis in fruit flies following elevations in
      temperature. More recently, a number of other environmental and pathological
      events have been observed to increase the expression of HSPs; consequently, they
      are also referred to as stress proteins. After expression of the stress genes,
      cells become resistant to subsequent stresses. This phenomenon has been termed
      "stress tolerance." The mechanisms by which stress tolerance is achieved are
      still poorly understood. Recent evidence suggests that stress tolerance is, at
      least in part, due to the stabilization of cellular processes such as protein
      synthesis. Expression of HSPs has been observed during clinically relevant
      situations, especially under conditions in which the delivery of oxygen is
      diminished (e.g., hemorrhage, ischemia). Since the expression of HSPs is part of
      the cellular defense system protecting cells from harmful conditions, the
      regulation of their expression may be useful as a preventative measure prior to
      surgical manipulations, such as organ transplantation.

PMID- 7583162
TI  - Hypoxia-associated proteins.
AB  - The vascular endothelium is an important mediator of vascular tone, angiogenesis,
      inflammatory-immune reactions, vascular permeability, and hemostasis. Thus, it
      plays an important role in the pathogenesis of numerous critical care processes,
      including septic shock, myocardial infarction, the adult respiratory distress
      syndrome, and acute tubular necrosis. Endothelial functions may be altered by
      changes in the local cellular environment, particularly changes in PO2. The
      ability of endothelial cells (EC) to not only sense, but also to adapt to, acute
      and chronic changes in PO2 is critical to maintaining endothelial metabolic
      functions and, in turn, to maintaining homeostasis, particularly in the critical
      care setting. Recent studies have shown that the EC is one of the more hypoxia
      tolerant mammalian cell types; however, the mechanisms by which ECs respond and
      adapt to hypoxia are unknown. Our laboratory has shown that cultured ECs exposed
      to hypoxia upregulate a set of stress proteins, termed hypoxia-associated
      proteins (HAPs), that are distinct from the classically described stress proteins
      induced by heat shock (heat-shock proteins) or glucose deprivation (glucose
      regulated proteins). We have recently identified one of these proteins as the
      glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Further
      studies have shown that GAPDH expression is regulated by hypoxia, primarily at
      the transcriptional level. Subcellular fractionation of hypoxic EC has shown that
      GAPDH is upregulated in the cytoplasmic fraction as would be expected with a
      glycolytic enzyme; however, a protein corresponding to GAPDH is also upregulated
      in the nuclear fraction. This suggests that the upregulation of GAPDH in EC
      during hypoxia is related to the potential nonglycolytic functions of this
      enzyme. Furthermore, the upregulation of GAPDH and the other HAPs (that have yet
      to be identified) may be related to the relative hypoxia tolerance of EC.

PMID- 7583163
TI  - Initial interaction of leukocytes within the microvasculature: deformability,
      adhesion, and transmigration.
AB  - Sequestration and migration of neutrophils in response to acute inflammation
      involve sequential steps, including delivery of cells to the site of
      inflammation, sequestration within the microvasculature, adhesion, and
      transmigration out of the vascular space into interstitial tissues. Soluble
      mediators released in the inflammatory milieu and into the circulation cause
      profound changes in leukocytes, both circulating and sequestered, as well as in
      the vascular endothelium promoting this leukocyte sequestration and adhesion.
      Although common mechanisms exist regulating leukocyte sequestration in the
      systemic and pulmonary microcirculations, important differences are also
      apparent. Alterations in cellular deformability appear to be most important in
      sequestration of neutrophils in the pulmonary capillaries because of the unique
      geometric and hydrodynamic conditions in the pulmonary microcirculation.
      Neutrophils undergo dramatic morphologic and functional alteration not only
      during these processes, but as a consequence of them. This can lead to the
      release of a substantive armamentarium of toxic mediators from activated
      leukocytes, including reactive oxygen species via the oxidative burst and
      secretion of proteolytic enzymes contained within granules. These toxic compounds
      can have profound and detrimental effects on host tissues, leading to pulmonary
      dysfunction and multiorgan failure.

PMID- 7583164
TI  - Epithelial dysfunction in acute lung injury.
AB  - More than a quarter century has passed since Ashbaugh and colleagues postulated
      that abnormalities of surfactant are causally related to the abrupt and severe
      organ dysfunction that occurs in individuals with acute lung injury (ALI). In
      this time, much progress has been made in expanding our understanding of the
      normal functions of the alveolar epithelium and how these functions may be
      disrupted in the context of ALI. Alveolar epithelial cells are a key structural
      component of the spatial separation of gas and plasma, essential for normal gas
      exchange in the lung. In addition, alveolar epithelial cells synthesize, secrete,
      and take up surfactant, which, by reducing surface tension, is a key determinant
      of intra-alveolar pressure. Surfactant is qualitatively and quantitatively
      abnormal in lung injury due to changes in synthesis, secretion, intra-alveolar
      metabolism, and biophysical inhibition by protein and lipid inhibitors. Alveolar
      epithelial cells also subserve additional host defense functions, such as
      modulation of lymphocyte, macrophage, and neutrophil function; production of
      prostanoids, complement proteins, and nitric oxide; and display of major
      histocompatibility complex II molecules and intracellular adhesion molecule-1.
      Although the physiologic and pathogenic significance of some these functions is
      not absolutely clear, they are of potential relevance in the context of lung
      injury, wherein they may participate in the process of alveolar injury and
      repair.

PMID- 7583165
TI  - The role of active Na+ transport by lung epithelium in the clearance of airspace
      fluid.
AB  - Clinical and laboratory-based studies of pulmonary edema have usually focused on
      the mechanisms responsible for the production of the edema and how therapeutic
      maneuvers can oppose or treat such processes. Recently, there has been increasing
      interest in the mechanisms involved in the clearance of airspace fluids. These
      studies have demonstrated that active transport of Na+ by the distal lung
      epithelium plays an important physiologic role in the clearance of pulmonary
      edema fluid. Specifically, the ability of the lung to clear its fluid by active
      transport processes correlates with survival from high-pressure or high
      permeability pulmonary edema. Also, studies have shown that immaturity of Na+
      transport processes and, specifically, inadequate expression of Na+ channels
      contribute to the pathogenesis of respiratory distress syndrome in the newborn.

PMID- 7583166
TI  - Control of vascular reactivity.
AB  - The two commonly recognized sequelae of acute lung injury (ALI) are pulmonary
      hypertension and arterial hypoxemia. The mechanism of the pulmonary hypertension
      is not precisely known, but undoubtedly is contributed to by both vasoactive
      mediators and pulmonary parenchymal structural changes. The pulmonary circulation
      is normally tightly controlled such that there is excellent matching of perfusion
      to ventilation through attenuation of hypoxic pulmonary vasoconstriction (HPV).
      In ALI, there is an attenuation of HPV and resulting areas of low
      ventilation/perfusion or shunt. The mechanism behind this abnormal pulmonary
      vascular contractility in disease is under investigation, but may involve the
      release of endogenous vasodilator mediators such as nitric oxide.

PMID- 7583167
TI  - Sepsis and multiple organ dysfunction syndrome: a clinical-mechanistic overview.
AB  - Multiple organ dysfunction syndrome (MODS) is the primary cause of death in
      patients admitted to ICUs. Despite the development of better resuscitation, more
      powerful antibiotics, and more sophisticated methods for organ support, our
      ability to rescue patients from established MODS has not improved significantly
      since the syndrome was first described two decades ago. Rapid advancements in
      molecular biology have begun to unravel some of the potential mechanisms behind
      the development of this syndrome, and have suggested many potential therapeutic
      approaches. To effectively use these new treatment options as they become
      available, it is necessary to have a clear understanding of how these therapies
      fit into the current theories on the pathophysiology of MODS. Thus, the goal of
      this article is to integrate what is new in our understanding of the development
      of MODS with current concepts regarding potential therapies of this complex and
      perplexing syndrome.

PMID- 7583168
TI  - Pathogenic effects of endotoxin.
AB  - Endotoxin is a lipopolysaccharide contained within the cell wall of Gram-negative
      bacteria. This molecule initiates a host inflammatory response to Gram-negative
      bacterial infection. An adequate inflammatory response likely enhances host
      survival by mediating clearance of infection and bacterial toxins. Unfortunately,
      this same host response can also produce dysfunction of multiple organ systems
      and mortality. This article focuses on the history of our understanding of the
      role of endotoxin in human septic shock. These pathophysiologic connections have
      led to therapies directed at endotoxin. Unfortunately, antiendotoxin therapy has
      not achieved significantly improved outcome in humans with severe sepsis. This
      may represent lack of antiendotoxin efficacy in the compounds used, or a failure
      of the investigative approach. Interest in antiendotoxin therapies persists,
      while investigators express more humility in their understanding of endotoxin's
      role in the pathophysiology of septic shock.

PMID- 7583169
TI  - Regulation of cytokine gene expression: tumor necrosis factor, interleukin-1, and
      the emerging biology of cytokine receptors.
AB  - Cytokines are bioactive molecules which mediate host responses to inflammatory
      stimuli. For cytokines to exert their effects, a number of molecular processes
      must occur. Inflammatory cells must sense the presence of a stimulus, often by
      detection of that stimulus via cell-surface receptors. Information detected at
      the cell surface must be transduced intracellularly, and the machinery of
      cytokine messenger RNA and protein synthesis initiated. Once secreted, cytokines
      must bind specific receptors on target tissues; these receptors in turn transduce
      signals which alter target cell phenotypes and responses. Each one of these steps
      is tightly regulated and may serve as a target for therapeutic manipulation. In
      this article, the regulation of cytokine gene expression is summarized, with
      particular emphasis on the regulation of tumor necrosis factor alpha and
      interleukin-1 biosynthesis. Attention is focused on therapeutic agents which
      alter cytokine production or activity, some of which are currently used in the
      ICU.

PMID- 7583171
TI  - Induction of the stress response to prevent organ injury.
AB  - Septic shock, multiorgan dysfunction, and the acute respiratory distress syndrome
      are major contributors to morbidity and mortality in the ICU setting. Animal
      studies have shown that these forms of injury can be attenuated or prevented if a
      phenomenon, called the stress response, is activated. The stress response,
      characterized by a transient downregulation of most cellular products and by the
      upregulation of the heat-shock proteins (HSPs), has been shown to provide
      protection to cells and experimental animals if triggered prior to an otherwise
      lethal injury. The mechanisms by which the stress response is protective are not
      known with certainty, but HSPs appear to play an important role. HSPs are
      constitutively present in all cells studied to date and can also be induced by
      artificial fever and by nonthermal means. They act as molecular chaperones,
      interacting transiently with newly synthesized proteins and proteins experiencing
      difficulty in proper folding. HSPs also escort and help proteins to cross
      membranes. This chaperone function is essential for cellular protection since it
      provides a mechanism by which defective polypeptides may be directed to lisosomes
      for degradation. This article summarizes the current literature on the effects of
      the stress response in protecting cells and animals from lethal forms of systemic
      and organ damage.

PMID- 7583170
TI  - Molecular biology of myocardial hypertrophy and failure: gene expression and
      trophic signaling.
AB  - Pressure-overload cardiac hypertrophy is associated with the re-expression of an
      ensemble of genes representative of embryonic myocardium, whose protein products
      modulate myocardial function. Regulation of cardiac-specific gene expression in
      end-stage myocardial disease in humans implies a pathophysiologic role for
      altered gene expression in the progression from compensatory hypertrophy to
      decompensated heart failure. The molecular signals that transduce load into a
      hypertrophic cardiac myocyte phenotype involve mechanical deformation and the
      local myocardial production of trophic factors, including angiotensin II, and
      transforming and fibroblast growth factors. Growth factors provoke a pattern of
      gene expression in cultured cardiac myocytes resembling that seen in pressure
      overload in vivo, in keeping with an autocrine or paracrine model of hypertrophy.
      Moreover, growth factor stimulation and pressure-overload hypertrophy share
      intracellular signaling pathways, including the activation of nuclear proteins
      encoded by cellular oncogenes. Elucidation of these signaling pathways may
      provide new therapeutic targets for the treatment of cardiac muscle disease that
      overcomes the limitations of currently available strategies.

PMID- 7583172
TI  - Heat shock and tissue protection.
AB  - Tissue injury, resulting from ischemia and reperfusion, is a common theme seen in
      many clinical disease processes. Conditions ranging from hemorrhagic shock in the
      young trauma victim to myocardial infarction in the elderly have, as part of
      their pathophysiology, some degree of ischemia and reperfusion. The conditions
      typical of modern organ preservation are extremely stressful and injurious to
      living tissues. Organ preservation is a model of ischemia and reperfusion unique
      to the medical field as it permits the opportunity for preventive interventions.
      The established fields of thermotolerance and heat-shock biology have focused
      their studies upon the understanding of the cellular response to hyperthermia.
      The knowledge gained from these two disciplines shows that the cellular response
      to heat is an example of a more generalized stress response. Following the acute
      heat-shock response, the cell rapidly acquires a state of temporary protection
      against injury due to heat and other noxious conditions such as ischemia and
      reperfusion. The studies described here illustrate that the purposeful induction
      of the heat-shock response in whole organs prior to procurement and preservation
      can successfully protect these tissues against preservation (ischemia) and
      transplantation (reperfusion) injuries.

PMID- 7583174
TI  - Antioxidant therapy in critical care medicine.
AB  - Antioxidant therapies are currently undergoing clinical trials to determine their
      benefit in a number of diseases seen in the critical care unit. It is
      particularly likely that their use will become standard therapy in a number of
      situations in which there is reperfusion injury following an ischemic episode.
      During the lag time from the conception of antioxidant interventions to their
      introduction into clinical practice, our understanding of how oxidant injuries
      are mediated has changed considerably. This understanding has allowed the
      development of more rational approaches to antioxidant therapy while exposing the
      limitations of some of the approaches currently being evaluated in a clinical
      setting. In addition, some existing therapeutic agents have previously
      unrecognized antioxidant and pro-oxidant effects. An inherent requirement of an
      effective antioxidant therapy is that such therapy is effective against the
      radicals being generated, and that sufficient quantities of the antioxidants used
      reach all sites of radical generation in time to limit tissue injury. Recent
      observations suggest that few, if any, of the currently known individual
      antioxidants can adequately meet these goals. However, combination therapy, or
      the development of synthetic compounds that can combine the properties of current
      antioxidants, may come close.

PMID- 7583173
TI  - Gene therapy in acute critical illness.
AB  - The development of techniques for manipulating nucleic acids and strategies for
      delivering DNA to humans has made gene therapy a reality. Although mostly focused
      on genetically based diseases so far, there is every reason to expand the concept
      to include acquired diseases. Critical illness may be a good target for gene
      therapy because of the high mortality and need for only transient treatment.
      Genes can be delivered in vivo using viral vectors (replication-deficient
      adenovirus and adeno-associated virus most often). Viral vectors have some
      negatives, mainly the triggering of an inflammatory and an immune response.
      Nonviral DNA delivery systems include liposomes (cationic or anionic), direct DNA
      injection, and polycation-DNA-glycoconjugates. Combining liposomes with viral
      components to deliver plasmids with a transgene may improve efficiency of
      delivery without causing toxicity. In a model of acute lung injury, in vivo
      delivery of a vector hyperexpressing the prostaglandin synthase gene using
      cationic liposomes resulted in increased production of prostaglandin E2 and
      prostacyclin in the lungs, and protected the lungs from the effects of endotoxin.
      This end-result demonstrates the feasibility of this approach. A similar
      rationale for the treatment of sepsis could be used. Other promising therapeutic
      genes would include those encoding antioxidant enzymes or antiproteases. The
      logistics for moving to initial studies of gene therapy in critically ill humans
      have been worked out for other diseases; such steps should expedite the
      exploration of this new category of therapies.

PMID- 7583176
TI  - Nitric oxide in the gut.
AB  - Nitric oxide (NO.) plays a central role in the physiology of the gastrointestinal
      tract and its response to critical illness. Potential sources of NO. in the gut
      include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle,
      neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes),
      reduction of luminal gastric nitrate, and denitrification by commensal anaerobes.
      The brain and endothelial isoforms of nitric oxide synthase are expressed under
      resting conditions, whereas inflammatory stimuli are required for the induction
      of the inducible type. Under resting conditions, mucosal perfusion is regulated
      by NO. derived from the vascular endothelium of the mesenteric bed. During
      inflammation, excessive NO. production from the inducible synthase may contribute
      to mucosal hyperemia. Coordination of peristalsis and sphincteric action is
      mediated by the release of NO., which acts as the principal neurotransmitter of
      the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel
      motility, such as ileus, result from excessive concentrations of NO. generated
      during endotoxicosis and inflammatory bowel disease. The role of NO. in the
      regulation of salt and water secretion is poorly understood. Endotoxin-induced
      inhibition of gastric acid secretion appears to be mediated by the action of NO.
      on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of
      stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early
      endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion
      to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell
      activation. Excessive NO., however, may directly injure the mucosa. Barrier
      function of the intestinal mucosa is protected by NO. in the early stages of
      injury, when neutrophil adhesion, ischemia, and mast cell activation are
      relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more
      advanced stages of inflammation, when activation of inducible NOS yields toxic
      concentrations of NO.. At high concentrations, NO. disrupts the actin
      cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and
      produces a hyperpermeable state. Selective inhibition of the inducible isoform of
      NOS and maintenance of the constitutive types may be therapeutic.

PMID- 7583175
TI  - Signaling events in monocytes and macrophages.
AB  - The cellular signaling events leading to the systemic inflammatory response
      syndrome and sepsis in monocytes/macrophages activated by lipopolysaccharide
      (LPS) are well understood. LPS is a glycolipid component of Gram-negative
      bacterial cell wall. It exerts its effect through the lipid A moiety. LPS binds
      to monocytes/macrophages via a membrane-bound receptor, CD14, an interaction
      which is optimized in the presence of plasma factors, LPS-binding protein, and
      septin. Although LPS is known to bind to other receptors, the roles of these
      receptors in transmembrane signaling and activation of monocytes/macrophages are
      not as well understood as is that of the CD14 receptor. Intracellular events in
      response to LPS stimulation are mediated by phospholipase (PL) C, protein
      kinases, PLA2, and PLD. Activation of PLC by LPS results in the release of
      diacylglycerol and inositol 1,4,5-trisphosphate. The former mediates the
      stimulation of protein kinase C, and the latter induces an increase in
      intracellular calcium concentration. LPS stimulation of monocytes/macrophages
      also results in the phosphorylation and activation of several protein kinases,
      including protein tyrosine kinases which mediate cytokine production, and mitogen
      activated protein kinase which activates cytosolic PLA2 to release arachidonate.
      LPS also plays a role in cellular proliferation and differentiation. Upregulation
      of the secretory form of PLA2 has also been documented in response to LPS. PLD is
      stimulated by LPS to release phosphatidic acid (PA). PA can activate the
      respiratory burst by increasing diacylglycerol production and by modulating the
      effects of guanine nucleotide-binding proteins. Therapeutic strategies to
      decrease the clinical effects of sepsis would logically include agents which
      block at initial receptor-ligand interaction, as well as those which attenuate
      the intracellular events that follow LPS stimulation. Early in vivo studies are
      promising, but clearly much work remains to be done.

PMID- 7583177
TI  - Osteoarthritis of the hand. New methods. New data.

PMID- 7583178
TI  - Sensitivity of radiographic features and specificity of scintigraphic imaging in
      hand osteoarthritis.
AB  - We undertook to determine which of the radiographic features most reliably
      detected the presence and disease progression in osteoarthritis in the hand; and
      which of the radiographic features corresponded with the radionuclide bone scan
      images. 32 patients with osteoarthritis had X 5 macroradiographs taken of their
      wrists and hands at 6 monthly intervals over an 18 month period. The high
      magnification and resolution of microfocal radiography permitted quantitative
      detection of the extent and change in joint space width, subchondral sclerosis,
      osteophytosis and juxtaarticular radiolucencies. 4-hour technetium 99m methylene
      bisphosphonate bone scans were taken at 0 and 12 months and the activity of the
      tracer uptake at each joint scored. The latter was compared with the radiographic
      features at each visit and the changes between visits analysed. In hand OA the
      most sensitive radiographic parameters for detecting disease were osteophytes,
      subchondral sclerosis and juxtaarticular radiolucencies, with radionuclide
      imaging demonstrating the increased activity in bone formation associated with
      the growth and remodelling of osteophytes. Changes in the number and size of
      osteophytes and joint space narrowing were the only reliable and sensitive
      parameters for assessing disease progression. We conclude that in osteoarthritis,
      the bony changes progress significantly before the occurrence of radiographically
      evident joint space narrowing indicative of cartilage thinning.

PMID- 7583179
TI  - Numerical scoring systems for the progression of osteoarthritis of the finger
      joints.
AB  - We developed methods to assess and to score progression of osteoarthritis (OA) of
      the distal and proximal interphalangeal (DIP and PIP) and metacarpophalangeal
      (MCP) finger joints. Thirty-six patients with osteoarthritis (OA) of the finger
      joints were followed for five years. Anteroposterior radiographs of the hands
      were obtained at the start of this prospective study and at yearly intervals. The
      scoring systems used were based on: -1- the increase in incidence of OA during
      consecutive years in previously normal joints. -2- the radiological progression
      of the anatomical lesions (changes in osteophyte growth, loss of joint space,
      subchondral cysts or sclerosis) in pathological finger joints. -3- the
      consecutive pathological phases recognized in the course of the disease.
      Significant increases in both the numbers of affected DIP, PIP and MCP joints per
      subject and the anatomical progression of the disease in the different finger
      joints of each individual patient were recorded during the 5-year follow-up. In
      approx. 40% of the patients the classical picture of OA was complicated by
      manifest erosive changes, which preceded a period in which repair phenomena in
      the 'eroded' finger joints led to generation of a new subchondral plate covered
      by cartilaginous tissue. Huge osteophytes were then responsible for the nodular
      aspect of the affected finger joints. OA of the finger joints in our patients was
      progressive in nature and went through predictable phases. Recognition and
      scoring of these phases allowed faster assessment of OA progression and led to
      the same conclusions as scoring the anatomical progression.

PMID- 7583180
TI  - The epidemiology of osteoarthritis of the hand.
AB  - The hand is a common site of osteoarthritis. Defining hand OA, particularly for
      epidemiological studies, has undergone reassessment and revision over the last
      few years. Although many studies to date have used a system of grading
      radiographic severity that was developed by Kellgren and Lawrence, there are
      significant problems with this system. In this paper we consider a number of
      alternative methods for grading hand OA including a scale which grades the
      individual joint features separately. Patterns of hand OA as well as the natural
      history and risk factors are also discussed.

PMID- 7583182
TI  - Validation of an algofunctional index for osteoarthritis of the hand.
AB  - Although hand osteoarthritis is common, it has been the focus of few therapeutic
      trials. In addition to the problems raised by clinical trials in osteoarthritis
      in general and to the difficulties due to the unforeseeable course of
      osteoarthritis of the trapezometacarpal and finger joints, the lack of a clinical
      tool for assessing pain and function over time is an additional obstacle. We
      propose an algofunctional index designed for evaluation and symptomatic follow-up
      of patients with digital osteoarthritis. The index is based on a physician
      administered questionnaire on 10 daily activities involving the hands. The
      patient is asked to answer each item using a 4-point verbal scale, from "possible
      without difficulty" (0) to "impossible" (3 points); thus, total scores range from
      0 to 30. This index has been used in a few clinical placebo-controlled trials and
      was found sensitive to change. The aim of this study was to assess the
      metrological qualities of this index, including consistency (internal and
      external), sensitivity and specificity (by scoring the index in different groups
      of subjects), intra-observer reproducibility, and ease of use. Three hundred
      patients were recruited by 25 rheumatologists: 100 had a painful attack of
      digital and/or trapezometacarpal osteoarthritis (mean age: 64.9 years) with a
      score of more than 40 mm on a visual analog scale for overall pain severity
      (mean: 57.3 +/- 14 mm), 100 had "inactive" hand osteoarthritis (mean age 67.0
      years), and 100 had no diseases of the upper limbs. Specificity/sensitivity: the
      mean index score was 12.41 +/- 5.41 in patients with painful OA, 4.28 +/- 3.87 in
      "inactive" cases, and 0.59 +/- 1.23 in controls. External consistency: the
      overall mean score was well correlated with pain severity: r = 0.49 (p < 0.001).
      Internal consistency: principal component analysis identified a primary axis
      responsible for 44.2% of the variance and two secondary axes each responsible for
      slightly more than 9% of the variance. None of the questions seemed redundant.
      Intra-observer reproducibility: two evaluations done one hour apart in
      symptomatic patients yielded the following scores: 12.32 +/- 5.41 and 12.5 +/-
      5.51 (correlation: 0.95; mean difference: 0.17 +/- 1.64; coefficient of
      variation: 9.32%). Kappa values for both measurements of each item ranged from
      0.68 to 0.87. Ease of use: mean time needed to determine the score 2.5 +/- 2 min.
      The scoring process was considered simple by 100% of investigators and easy/very
      easy by 98% of patients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7583183
TI  - Methodology of clinical trials in hand osteoarthritis. Issues and proposals.
AB  - Although very common, hand osteoarthritis has rarely been the focus of clinical
      trials aimed at determining whether old or new drugs are effective on its
      symptoms or anatomical course. In addition to the difficulties inherent to
      studies of osteoarthritis in general, the highly unpredictable course of hand
      osteoarthritis poses specific challenges. Hand osteoarthritis is only beginning
      to be considered a potentially useful model for therapeutic trials and clinical
      research, in addition to the two widely-used models, knee and hip osteoarthritis.
      Recent studies have provided new information on the clinical and roentgenographic
      course of hand osteoarthritis. An algofunctional index and a quantitative
      roentgenographic score have been developed and validated as tools for evaluating
      and monitoring hand osteoarthritis. These tools are now available for use during
      therapeutic trials. In this article, we will make a number of recommendations
      about the selection of patients and of quantitative evaluation methods. These
      recommendations take into account the specific features of hand osteoarthritis
      and of the various categories of drugs for osteoarthritis; they place special
      emphasis on the most recent drug classes, namely symptomatic slow-acting drugs
      for osteoarthritis and potentially "chondroprotective" agents.

PMID- 7583184
TI  - Etiologic factors in finger osteoarthritis.
AB  - Etiological factors in finger osteoarthritis are both local (single injury or
      repetitive joint use) and general. Epidemiological studies, twin studies, and
      studies of the ethnic influence have established that genetic factors play a
      role. The disease is more common in postmenopausal women, suggesting an influence
      of hormonal factors. Findings from studies of associations between finger
      osteoarthritis and osteoarthritis at other sites (spine, hips, knees),
      hyperostosis, and obesity, as well as the fact that the disease is less common in
      patients with osteoporosis and absent in hemiplegia, suggest that the concept of
      "osteoarthritic disease" is relevant.

PMID- 7583181
TI  - Therapeutic trials in digital osteoarthritis. A critical review.
AB  - Although common, hand osteoarthritis is controversial and rarely used as a model
      for clinical trials in osteoarthritis. We found only 13 therapeutic trials
      conducted in digital or trapeziometacarpal osteoarthritis between 1983 and 1994.
      Eleven of these trials were published. Seven were on nonsteroidal
      antiinflammatory drugs given either per os (two trials, meclofenamate and
      ibuprofen) or percutaneously (one trial each on etofenamate, ibuprofen, and
      ketoprofen gel, and two trials on niflumic acid gel), three were on symptomatic
      slow-acting drugs (glycosaminoglycanes in two trials and chondroitin sulfate in
      one), and three were on miscellaneous agents (the muscle relaxant idrocilamide,
      as a gel; the antisubstance P agent capsaicin, also as a gel; and a spa
      treatment). We have reviewed the methodology and findings of these trials with
      the goal of determining the optimal approach to realize better standardized
      trials in the next future for identifying symptomatic slow-acting drugs and/or
      "chondroprotective" agents with beneficial effects in digital osteoarthritis.

PMID- 7583185
TI  - Variables and events in the syntax of agrammatic speech.
AB  - This paper examines aggrammatics' interpretation of quantificationally ambiguous
      sentences. Although agrammatics are capable of recognizing quantificational
      ambiguities, they ascribe nonstandard entailments to those sentences involving
      universal quantification. Since quantificational ambiguity arises from movement
      of quantifiers at LF, doubt is cast on accounts of agrammatic behavior that rely
      on an inability to interpret moved constituents. Furthermore, the agrammatics are
      seen to improve in their thematic interpretation of arguments in reversible
      passive constructions and relatives if one of the arguments is universally
      quantified. The nonstandard entailments and improved performance on passive and
      relatives are accounted for via an elaboration of event semantics in which we
      propose that the agrammatic treats the event variable associated with a verb as
      nominal.

PMID- 7583186
TI  - Levels of representation and units of access relevant to agrammatism.
AB  - The paper differentiates argument structure from other levels of representation
      and uses linguistic analysis of aphasic narrative production to support an
      enriched lexical entry for verbs that includes the d-structure representation of
      the configuration of the verb, its arguments, and any other lexically selected
      material. A single narrative production study and portions of two follow-up
      studies are presented. The argument structure distributions for two agrammatics
      (with varying degrees of fluency) and a nonagrammatic conduction aphasic with
      anomia are compared and contrasted with both matched controls and each other.

PMID- 7583187
TI  - Training sentence production in agrammatism: implications for normal and
      disordered language.
AB  - This paper presents an overview of our work concerned with treatment of sentence
      production deficits seen in agrammatic (Broca's) aphasic individuals. Using a
      single-subject experimental research paradigm, we examined emergent sentence
      production patterns in a subset of Broca's subjects who evinced sentence
      production (and comprehension) deficits involving "complex" sentences in which
      noun phrases (NPs) have been moved out of their canonical positions. We used
      aspects of Chomsky's Principles and Parameters approach of Government Binding
      (GB) Theory (Chomsky, 1986, Chomsky & Lasnik, 1991), as well as findings from the
      psycholinguistic and neurolinguistic literature as a basis for selecting
      sentences entered into our experiments and for designing our intervention
      approach, in general. Subjects were trained to produce sentences which rely on NP
      movement (i.e., passives) or WH-movement (i.e., wh-questions, object clefts)-
      sentences formed by applying the rule "Move-alpha" in which moved constituents
      leave behind a "trace" or "gap" of their movement. Training emphasized the
      lexical and syntactic properties (e.g., thematic role assignment, NP-movement) of
      target sentences. Throughout this training we carefully measured generalization
      to untrained sentences relying on similar movement operations and error patterns
      were examined as they evolved over time. Results of our work indicated not only
      improved sentence production abilities in all subjects under study, but also--in
      many cases--generalization of sentence production across linguistic lines. That
      is, training WH-movement structures (e.g., object clefts) improved production of
      untrained WH-movement constructions (e.g., wh-questions) that are very different
      in their s-structure representation; however, no effect of this training on NP
      movement structures occurred. In addition, within the class of wh-questions,
      generative production across questions relying on argument (direct object NP)
      movement (i.e., what- and who-questions) occurred in the absence of
      generalization to wh-questions requiring movement from adjunct position (i.e.,
      where- and when-questions) for some subjects. For others, generalized production
      occurred only when wh-morphemes were the focus of treatment, indicating that at
      least two processes must be completed for successful wh-question production to
      take place: movement of the wh-item itself and control of sublexical features
      that determine wh-morpheme selection. These data are discussed in terms of the
      contribution that detailed recovery data, controlled for lexical and syntactic
      properties of sentence production, can make both to understanding the nature of
      sentence production deficits and to issues regarding normal sentence production.

PMID- 7583188
TI  - Syntactic processing in aphasia.
AB  - In this report we comment upon subject selection and methodology, and we describe
      some recent studies of syntactic processing in aphasia. Our data show that, like
      neurologically intact subjects, Wernicke's patients reactivate moved constituents
      (instantiate coreference) at the site of their extraction (even for sentences
      that they do not understand). Broca's patients, by constrast, are shown not to
      create such syntactically governed links (even for sentences that they do
      understand). These data isolate the processing bottleneck in Broca's aphasia and
      more generally suggest that syntactic comprehension limitations can be traced to
      changes in cortically localizable resources that sustain lexical processing.

PMID- 7583190
TI  - The time course of syntactic activation during language processing: a model based
      on neuropsychological and neurophysiological data.
AB  - This paper presents a model describing the temporal and neurotopological
      structure of syntactic processes during comprehension. It postulates three
      distinct phases of language comprehension, two of which are primarily syntactic
      in nature. During the first phase the parser assigns the initial syntactic
      structure on the basis of word category information. These early structural
      processes are assumed to be subserved by the anterior parts of the left
      hemisphere, as event-related brain potentials show this area to be maximally
      activated when phrase structure violations are processed and as circumscribed
      lesions in this area lead to an impairment of the on-line structural assignment.
      During the second phase lexical-semantic and verb-argument structure information
      is processed. This phase is neurophysiologically manifest in a negative component
      in the event-related brain potential around 400 ms after stimulus onset which is
      distributed over the left and right temporo-parietal areas when lexical-semantic
      information is processed and over left anterior areas when verb-argument
      structure information is processed. During the third phase the parser tries to
      map the initial syntactic structure onto the available lexical-semantic and verb
      argument structure information. In case of an unsuccessful match between the two
      types of information reanalyses may become necessary. These processes of
      structural reanalysis are correlated with a centroparietally distributed late
      positive component in the event-related brain potential.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7583189
TI  - Lexical properties, prosody, and syntax: implications for normal and disordered
      language.
AB  - This paper is primarily about sentence processing in neurologically intact
      subjects--but carries with it the underlying message that though both grammatical
      and on-line analyses of agrammatism have borne considerable fruit, there is much
      about the efforts from normal psycholinguistics that has yet to find its way into
      investigations of aphasia. We describe some of our psycholinguistic work and show
      how it has influenced our work in aphasia. This work involves three different
      kinds of information that the human sentence processing system appears to
      exploit: (1) lexical properties, particularly those having to do with verbs; (2)
      syntactic operations that connect one position in the sentence to another,
      nonadjacent position; and (3) prosody, which is often overlooked but which may
      turn out to be crucial to accounts of both normal and disordered sentence
      processing. Finally, we suggest that lexical properties interact with prosody to
      help the parser in its initial analysis.

PMID- 7583191
TI  - A time-based approach to agrammatic production.
AB  - A time-based approach to agrammatic speech is presented. The paper consists of
      three parts. In the first part, the literature which deals with agrammatic
      comprehension as a problem of disrupted timing, that is, as a slow-down of
      syntactic computation and/or a rapid decay of the results of syntactic
      processing, is reviewed. In a second part, the hypothesis that similar timing
      problems cause difficulties in production as well is discussed. Two possible ways
      in which this can happen are described. First, slow down or rapid decay can lead
      to desynchronization within the process of syntactic tree formation. Second, a
      slow down of syntactic processing can cause asynchrony between the production of
      a syntactic slot and the retrieval of the proper grammatical morpheme from the
      mental lexicon. This hypothesis predicts that morphemes which are dependent on a
      relatively complex part of the syntactic tree will elicit relatively many errors.
      Results from the literature which seem to confirm this prediction are discussed.
      In the third part of the paper, the possible ways in which a patient can adapt to
      the reduced temporal window that would result from a timing deficit are
      discussed. Message simplification will reduce the size of the required temporal
      window and will therefore have a beneficial effect on the error rate. Restart of
      the computational process will profit from previously reached activation levels
      so that synchrony is easier to reach and error rate is reduced. Empirical work
      which appears to support these hypotheses is reviewed.

PMID- 7583192
TI  - On the relation between representational and processing models of asyntactic
      comprehension.
AB  - Most accounts of asyntactic comprehension fall along a spectrum from pure
      representational accounts to pure processing accounts. The double dependency
      hypothesis of Mauner, Fromkin, and Cornell (1993) is an example of the former,
      while the SYNCHRON model of Haarman and Kolk (1991; see also Kolk, this volume)
      is an example of the latter. This paper attempts to demonstrate some of the ways
      that these two approaches interact. We introduce GENCHRON, a computer model based
      on Haarman and Kolk's SYNCHRON. GENCHRON is a parser subject to the kinds of
      processing deficits examined in Haarman and Kolk (1991). We present a simple
      grammar which leads GENCHRON to produce the kinds of semantic representations
      which Mauner, Fromkin, and Cornell (1993) propose for asyntactic comprehenders.

PMID- 7583193
TI  - Issues arising in contemporary studies of disorders of syntactic processing in
      sentence comprehension in agrammatic patients.
AB  - This paper reviews recent studies of sentence comprehension in agrammatic
      patients. The conclusion is reached that more detailed study of individual
      patients is necessary to support hypotheses that have been presented concerning
      the deficit in these patients and that the rationale for studying comprehension
      in this group of patients is not well developed. A set of suggested criteria is
      presented for patient analysis in this field.

PMID- 7583194
TI  - Examining the empirical and linguistic bases of current theories of agrammatism.
AB  - This paper, which is organized into five sections, critically examines the
      empirical support and linguistic assumptions underlying several current accounts
      of language disturbances in Broca's aphasia. In the first section, following a
      discussion of the use of signal detection methodologies in investigating
      grammatical sensitivity, the reliability of results from two studies that suggest
      that Broca's aphasic patients are differentially sensitive to grammatical
      constraints is examined. It is concluded that in some cases, claims of intact
      sensitivity are not supported. The second section examines the empirical support
      for the hypothesis that agrammatic patients are unable to compute syntactic
      dependency relationships because of slowed lexical processing. It is argued that
      the statistical treatment of the data and interpretive problems associated with
      the lexical decision paradigm undermine this hypothesis. In the third section,
      some of the linguistic assumptions underlying criticisms of chain-disruption
      hypotheses are examined. It is concluded that these criticisms are based on
      arguable linguistic assumptions. In the fourth section, it is argued that the
      linguistic and empirical support for both earlier and revised versions of
      Grodzinsky's default interpretive strategy is lacking. Methodological and
      conceptual shortcomings arising from this proposal are also discussed. In the
      final section, potential relationships between disordered language and currently
      developing models of normal language processing are discussed.

PMID- 7583195
TI  - The elusive character of agrammatism.
AB  - Traditionally, agrammatism was viewed as a restricted disorder of speech
      production which was associated with Broca's aphasia. This view has been replaced
      by a more complex picture which involves a range of linguistic impairments in
      both language production and comprehension. These disorders have been variously
      characterized as deficits, in the representation of linguistic structures and
      deficits in the on-line computation of sentence structures and their
      interpretations. A variety of analyses of production and comprehension in
      agrammatism, invoking both representational and computational analyses, are
      reviewed. Each has inadequacies, but, at the same time, it is argued that each
      also advances the understanding of agrammatism.

PMID- 7583196
TI  - Septo-hippocampal cholinergic system under the discrimination learning task in
      the rat: a microdialysis study with the dual-probe approach.
AB  - To investigate regulation of the septo-hippocampal cholinergic system by
      dopaminergic inputs to the septum in rats which performed a discrimination
      learning task, an in vivo microdialysis method with the dual-probe approach was
      used. Rats were trained to discriminate between lamp-on and -off states under an
      operant-type learning procedure. After stable discriminative behavior was
      established, dialysis probes were implanted into the hippocampus and the lateral
      septum area of each rat. The concentration of dopamine (DA) in the septum rapidly
      increased within 20 min after the beginning of a learning session. However,
      another group of rats trained on a similar but non-discriminative task showed no
      such increase. The concentration of acetylcholine (ACh) in the hippocampus was
      significantly enhanced during the learning session and rapidly returned to the
      basal value after the session, but showed a delayed and diminished increase in
      the non-discrimination group. These results suggest that DAergic inputs to the
      septum may be involved in control of the septo-hippocampal cholinergic system
      which is of importance for discrimination learning behavior.

PMID- 7583197
TI  - Regulation of extracellular adenosine levels in the striatum of aging rats.
AB  - Extracellular adenosine concentrations, evaluated by microdialysis in the
      striatum of young and aged rats, were 66.8 +/- 0.7 and 71.6 +/- 1.0 nM,
      respectively. The adenosine deaminase inhibitor EHNA (100 microM) increased the
      extracellular adenosine levels in young rats only. The adenosine kinase inhibitor
      iodotubercidin (10 microM) brought about the same increase in young and aged
      rats. In aged rats the resting adenosine outflow was reduced by the N-methyl-D
      aspartate (NMDA) receptor antagonist D-(-)-2-amino-7-phophonoheptanoic acid (D
      AP7) (1 mM). It is concluded that extracellular levels of adenosine in the
      striatum are not affected by age, irrespective of the differences in adenosine
      deaminase activity and that the release of excitatory amino acids is responsible
      for much of resting adenosine outflow in aged but not in young rats.

PMID- 7583198
TI  - Alterations in the action potential of Aplysia neurons evoked by a phorbolester
      are mediated by protein kinase C.
AB  - Alterations in the parameters of action potentials upon changes in protein kinase
      C (PKC) activity were studied on neurons of the visceral ganglion of Aplysia
      californica. The amplitude and maximum speed of the up-and downstroke of the
      action potentials (APs) were measured. Intracellularly injected PKC and intra-
      and extracellularly applied phorbol-12,13-diacetate (PDAc) had similar effects on
      the Aplysia neurons, the most prominent being an increase of the upstroke speed
      of the AP in every neuron. The non-PKC-activating 4 alpha-phorbol didecanoate had
      no effect, and the effects of the PKC blocker H-7 were opposite to those of PDAc.
      It was concluded that the changes of the AP evoked by PDAc are mediated through
      PKC activation.

PMID- 7583199
TI  - Alterations in GABAA receptor binding in the prefrontal cortex following exposure
      to chronic stress.
AB  - The present study was designed to examine the effects of chronic stress on GABAA
      receptor binding. Animals were randomly assigned to either a control, acute, or
      chronic stress condition and changes in specific binding were assessed using the
      GABAA receptor antagonist [3H]SR 95531. Exposure to chronic restraint stress led
      to a significant reduction in GABAA receptor binding in the prefrontal cortex.
      Alterations in specific binding were not observed in the cerebellum, caudate
      putamen, hippocampus, or cingulate cortex however, suggesting that the effects of
      chronic stress may be regionally specific. Exposure to acute restraint did not
      lead to a significant alteration in [3H]SR 95531 binding in any brain region
      examined.

PMID- 7583200
TI  - Short-term and long-term effects of p-chloroamphetamine on hippocampal serotonin
      and corticosteroid receptor levels.
AB  - Hippocampal corticosteroid receptors are regulated by corticosterone as well as
      by neurotransmitters, such as serotonin (5-HT). Studies have demonstrated that
      long-term changes in 5-HT levels are associated with alterations in hippocampal
      glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) number. However,
      the effect of short-term manipulations of 5-HT levels on hippocampal
      corticosteroid receptor levels has not been thoroughly investigated. The present
      set of studies examined the effect of para-chloroamphetamine (PCA) administration
      on both short-term and long-term regulation of hippocampal 5-HT and
      corticosteroid receptor levels. PCA is a selective serotonergic neurotoxin which
      initially releases 5-HT to cause a short-term depletion of 5-HT stores, followed
      by a long-term decrease in 5-HT levels which presumably reflects the destruction
      of 5-HT nerve terminals. In the initial study rats were adrenalectomized and 24 h
      later injected with PCA (20 mg/kg) and sacrificed 3 h later. PCA produced a large
      decrease in hippocampal 5-HT (-79%) and 5-hydroxyindoleacetic acid (5-HIAA) (
      40%) concentrations. In addition, PCA significantly decreased both hippocampal GR
      (-28%) and MR (-35%) levels. Pretreatment with fluoxetine (20 mg/kg), which
      presumably blocks the uptake of PCA into 5-HT nerve terminals, completely blocked
      the PCA-induced decreases in both 5-HT and corticosteroid receptor
      concentrations. In a final experiment, the long-term (7 days) effect of PCA
      administration on hippocampal 5-HT and corticosteroid receptor levels was
      examined. PCA (10 mg/kg given on 2 consecutive days) was administered to adrenal
      intact rats which were adrenalectomized 6 days later and subsequently sacrificed
      following a 24 h interval. PCA produced an 87% decrease in hippocampal 5-HT and 5
      HIAA levels, but did not alter hippocampal GR or MR levels.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7583201
TI  - Ventral pallidal GABA-A receptors regulate prepulse inhibition of acoustic
      startle.
AB  - Prepulse inhibition (PPI) of the acoustic startle reflex occurs when a weak
      auditory stimulus is presented 30-500 ms before the startling stimulus. Previous
      studies have shown that PPI is modulated by GABAergic projections from the
      ventral striatum to the ventral pallidum (VP). To evaluate the anatomical and
      pharmacological substrates of pallidal modulation of PPI, we measured PPI after
      intrapallidal infusion of GABA-B and GABA-A antagonists. Intrapallidal infusion
      of the GABA-B antagonist, 2-OH-saclofen (0.025-0.10 microgram), did not
      significantly alter PPI, startle amplitude or peak startle latency. Infusion of
      the GABA-A antagonist, picrotoxin (0.02-0.08 microgram), into the medial or
      central VP significantly reduced PPI; this effect appeared somewhat weaker after
      picrotoxin infusion into the lateral VP and was absent after infusion into the
      adjacent fundus striatum (FS). There was no significant effect of picrotoxin
      infusion into any of the VP sites or FS on startle amplitude or peak startle
      latency. Thus, ventral striato-pallidal GABAergic modulation of PPI appears to be
      mediated solely by GABA-A receptors and this modulatory substrate is
      predominantly distributed across the medial and central portions of the VP.

PMID- 7583202
TI  - Nitric oxide synthase immunoreactivity and NADPH diaphorase staining are co
      localised in neurons closely associated with the vasculature in rat and human
      retina.
AB  - Nitric oxide synthase (NOS) is widely distributed throughout the nervous system
      and is found in neurons which produce nitric oxide (NO). In attempting to
      elucidate the biological roles of NO in neurotransmission, vasodilation, and in
      neurodegeneration, nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPHd) histochemistry has been widely used. NADPHd histochemistry and NOS
      immunoreactivity (NOS-IR) have been assumed to stain the same population of
      neurons. However, there have been numerous reports which suggest that this may
      not always be the case, and in all neuronal populations investigated, the
      coincidence of NOS and NADPHd must be unequivocally demonstrated. We have
      examined NADPHd histochemistry and NOS immunoreactivity in the human and rat
      retina and shown that these are 100% co-localised. Further, we have described the
      morphology of NADPHd and NOS-IR neurons in the human and rat retina and shown a
      close association of these neurons and their processes to the retinal
      vasculature. We have taken the NOS-IR to the ultrastructural level and have
      identified NOS-IR cells in close association with the basal lamina covering
      endothelial cells and pericytes of the retinal capillaries. We suggest that NO
      released from these neurons may be involved in the regulation of retinal
      microcirculation.

PMID- 7583203
TI  - Four-day hyperinsulinemia in euglycemic conditions alters local cerebral glucose
      utilization in specific brain nuclei of freely moving rats.
AB  - Although insulin is a well known regulator of peripheral tissue glucose
      metabolism, there is little agreement over its effects on brain glucose
      metabolism. Several investigators report that peripheral insulin may enter the
      brain via several routes. The presence of insulin receptors specific to brain,
      coupled to diverse reports of the effect of acute insulin administration on brain
      glucose use, led us to carry out a 4-day hyperinsulinemic euglycemic clamp in
      freely moving rats with subsequent labelled 2-deoxyglucose metabolic mapping
      studies. It was found that after 4 days of peripheral insulin infusion, several
      brain regions (Anterior Hypothalamic area, Suprachiasmatic nucleus, Basolateral
      Amygdaloid nucleus, Supramammillary bodies, Medial Geniculate nucleus and Locus
      Coeruleus) had an altered local cerebral glucose utilization. Upon subsequent
      analysis of their anatomical and functional connections it is proposed that
      insulin may regulate an integrated circuit of pathways within the central nervous
      system.

PMID- 7583204
TI  - cAMP accumulation in the hypothalamus, cerebral cortex, pineal gland and brown
      fat across the wake-sleep cycle of the rat exposed to different ambient
      temperatures.
AB  - The concentration of adenosine 3':5' cyclic monophosphate (cAMP) was determined
      in the anteroventro-medial hypothalamus, the cerebral cortex, the pineal gland
      and the interscapular brown adipose tissue, during the different stages of the
      wake-sleep cycle of rats kept, under a 12-12-h light-dark cycle, in different
      environmental conditions, i.e., control (47-52 h at ambient temperature (Ta) 23
      +/- 0.5 degrees C), exposure (47-52 h at Ta 0 +/- 1 degree C) and recovery (1-4 h
      at Ta 23 degrees C after 48 h at Ta 0 degree C). The results show that cAMP
      concentration consistently changed: (1) during the wake-sleep cycle in the
      anteroventro-medial hypothalamus, decreasing from wakefulness to sleep; (2)
      during the dark-light transition in the pineal gland, increasing with the onset
      of the light phase; and (3) with the environmental condition in the interscapular
      brown adipose tissue increasing, with respect to the control condition, in
      exposure and recovery. No significant changes in cAMP concentration were observed
      in the cerebral cortex.

PMID- 7583205
TI  - Direct projection from the suprachiasmatic nucleus to hypophysiotrophic
      corticotropin-releasing factor immunoreactive cells in the paraventricular
      nucleus of the hypothalamus demonstrated by means of Phaseolus vulgaris
      leucoagglutinin tract tracing.
AB  - The diurnal rhythm of the activity of the hypothalamo-pituitary-adrenal axis is
      generated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN).
      However, the neuronal circuit connecting the SCN with the neurosecretory
      corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of
      the hypothalamus is not clear. To investigate the existence of a direct link
      between the SCN and the CRF neurons in the PVN we combined microiontopheretic
      injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L)
      into the SCN with immunohistochemical detection of CRF in adrenalectomized male
      rats. The majority of the PHA-L-ir axons originating from the SCN terminated in
      the subparaventricular area. A minor contingent of fibers continued into the PVN
      proper, involving the medial and dorsal parvicellular subnuclei of the PVN. All
      PHA-L injections involving the entire SCN gave rise to PHA-L positive fibers
      endowed with boutons en passage and terminal boutons contacting CRF positive cell
      bodies in the PVN. Notably, varicosities on the PHA-L labelled fibers were
      present in close proximity to cell bodies and proximal dendrites of a subportion
      of the CRF neurons located in the periphery of the CRF cell cluster. The present
      study provides the first evidence to suggest a direct connection between the SCN
      and the CRF producing neurons of the hypothalamo-pituitary-adrenocortical axis in
      the PVN. Considering the sparse number of PHA-L-ir varicosities in close
      proximity to the CRF-ir cells, it seems likely that this direct pathway
      constitutes but a part of a projection system from the SCN, possibly involving
      multisynaptic pathways, influencing the hypothalamo-pituitary-adrenocortical
      axis.

PMID- 7583206
TI  - Tau protein is altered by focal cerebral ischaemia in the rat: an
      immunohistochemical and immunoblotting study.
AB  - Breakdown of the cytoskeleton may be involved in the evolution of ischaemic brain
      damage and alterations in microtubule-associated proteins may play an important
      role in this process. In the present study, tau, a microtubule-associated protein
      predominantly located in axons, was examined after 2 or 6 h of focal cerebral
      ischaemia in the rat. Immunohistochemistry revealed increased Tau1 staining in
      the neuropil, some perikarya and in glial cells throughout the dorsolateral
      caudate nucleus and ventrolateral neocortex in the ipsilateral hemisphere at both
      2 and 6 h after occlusion of the middle cerebral artery. Contrastingly,
      immunostaining of another tau antibody, TP70, was unchanged in the neuropil, but
      was increased specifically in glial cells in these regions. Immunoblotting
      revealed the presence of additional tau bands in tissue extracts of the caudate
      nucleus and ventrolateral neocortex ipsilateral to the occluded middle cerebral
      artery as detected by both tau antibodies after either 2 or 6 h. The results
      suggest that tau is dephosphorylated and/or degraded in axons and some neuronal
      perikarya in response to focal cerebral ischaemia. In contrast to the response in
      neurons, increased immunoreactivity of both tau antibodies in glial cells
      indicates a differential response of neuronal and glial tau to focal cerebral
      ischaemia.

PMID- 7583208
TI  - Comparison of the antinociceptive and antispastic action of (-)-baclofen after
      systemic and intrathecal administration in intact, acute and chronic spinal rats.
AB  - Baclofen is particularly effective in treating spasticity of spinal origin in
      humans. However, most investigations of this drug in animals have only assessed
      its antinociceptive effect, presumably because of the difficulty in developing
      animal models of spasticity. This study attempted to evaluate both, the
      antinociceptive and antispastic action of (-)-baclofen (the more active
      enantiomer) by incorporating the chronic spinal preparation, in which spasticity
      gradually develops following spinal transection. Separate groups of intact, acute
      (1 day) or chronic (20-25 days) spinal rats were pretested on the nociceptive
      tail-flick (TF) assay prior to either subcutaneous (SC; 1-30 mg/kg) or
      intrathecal (IT; 0.1-12 micrograms) injection of (-)-baclofen and retested at
      specific post-injection intervals. Hindlimb spasticity was elicited in chronic
      spinal rats by mechanical stimulation to the abdomen. Because the clinical use of
      baclofen generally involves chronic administration, both responses were tested
      for 3 successive days to assess tolerance. Results confirmed the analgesic effect
      of SC and IT (-)-baclofen in intact rats. As previously reported, the
      antinociceptive effect of IT (-)-baclofen was increased in acute spinal rats.
      However, three weeks after spinalization there was a profound decrease in this
      response. In contrast, antinociception produced by SC (-)-baclofen was reduced in
      acute and chronic spinal rats compared to intact animals; but there was no
      difference between the acute and chronic conditions. In spite of this
      differential decrease in antinociception after IT, relative to SC,
      administration, both routes of administration produced an antispastic effect in
      chronic spinal rats. There was no antinociceptive tolerance to SC administration
      and only minimal tolerance to IT (-)-baclofen (in intact rats); the antispastic
      effect did not become tolerant. A peripheral action might explain the dichotomy
      between SC and IT (-)-baclofen in regard to antinociception. However, further
      research is needed to determine why both routes of administration were effective
      against spasticity while only SC (-)-baclofen retained an antinociceptive action
      in chronic spinal rats.

PMID- 7583207
TI  - Apoptotic cell death of a temperature-sensitive central neuronal cell line.
AB  - A neuron-like cell line HS-2, derived from a primary fetal rat (E17) hippocampal
      cell culture using the temperature-sensitive SV 40 large T antigen, exhibits flat
      shape and grows well in culture medium with 5% fetal calf serum (FCS) at the
      permissive temperature (PT, 33.5 degrees C). At the non-permissive temperature
      (NPT, 38.5 degree C), many, but not all cells, have a neuronal shape with
      processes. The addition of dibutyryl-cAMP promotes the morphological changes in
      the cells to a neuron-like shape with long neurite-like processes and the cells
      exhibit neuron-specific enolase- and glutamic acid decarboxylase
      immunoreactivity. Apoptotic cell death also occurs in these cultures at the NPT.
      DNA fragmentation and chromatin condensation that are characteristic of apoptosis
      occur within 8 h of being placed at the NPT. By 48 h after being placed at the
      NPT, the number of surviving cells decreases by 40% in the presence of 5% FCS.
      This cell line should be useful for investigating the mechanisms of 'programmed
      cell death' of neurons, which appears to occur during brain development and
      possibly in CNS degenerative diseases.

PMID- 7583209
TI  - Hyperactivity of central noradrenergic and CRF systems is involved in social
      isolation-induced decrease in pentobarbital sleep.
AB  - The modulatory effects of the central noradrenergic and CRF systems on the
      pentobarbital-induced hypnotic activity were investigated in socially isolated
      mice. Pentobarbital-induced sleeping time decreased depending on the duration of
      isolation period and reached the minimum at 4 weeks after the isolation. The
      intermale aggressive behavior tested in isolated mice increased along with the
      decrease of hypnotic activity of pentobarbital. I.c.v. injection of CRF
      (corticotropin-releasing factor; 0.6-2.1 nmol) and i.p. injection of yohimbine
      (0.5-1 mg/kg), an alpha 2-adrenoceptor antagonist, significantly decreased the
      pentobarbital-induced sleeping time in group-housed but not in socially isolated
      mice while alpha-helical CRF9-41 (alpha hCRF; 3.3-6.5 nmol i.c.v.), a CRF
      antagonist, and clonidine (12.5-100 micrograms/kg i.p. and 7.5-15 nmol i.c.v.),
      an alpha 2-adrenoceptor agonist, recovered the hypnotic activity of pentobarbital
      decreased by social isolation to the level in group-housed mice without changing
      the activity observed in group-housed animals. alpha hCRF (6.5 nmol i.c.v.)
      significantly abolished the yohimbine (1 mg/kg i.p.)-induced decrease in the
      hypnotic activity of pentobarbital in group-housed mice. Propranolol (50-100 nmol
      i.c.v. and 5-10 mg/kg i.p.), a beta-adrenoceptor antagonist, and prazosin (5-10
      nmol i.c.v. and 250-500 micrograms/kg i.p.), an alpha 1-adrenergic antagonist,
      significantly and dose-dependently recovered the hypnotic activity of
      pentobarbital in socially isolated mice to the level in group-housed
      mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583210
TI  - Calcium/calmodulin-dependent protein kinase II and protein phosphatase 2B
      (calcineurin) immunoreactivity in the rat hippocampus long after ischemia.
AB  - Calcium/calmodulin-dependent protein kinase II (kinase II) and protein
      phosphatase 2B (calcineurin) immunoreactivity in the rat hippocampus was studied
      100 days after ischemic damage to hippocampal CA1 pyramidal neurons. One-hundred
      days after ischemia, only a few CA1 pyramidal neurons survived and they exhibited
      enhanced kinase II and calcineurin immunoreactivity in their basal and apical
      dendrites. The stratum lucidum of the CA3 (mossy fiber terminal area) had
      enhanced kinase II and calcineurin immunoreactivity. These results suggest
      activity-dependent regulation and redistribution of kinase II and calcineurin
      after intervention in neuronal circuitry.

PMID- 7583211
TI  - Nitro-L-arginine augments the endothelin-1 content of cerebrospinal fluid induced
      by cerebral ischemia.
AB  - The effect of nitro-L-arginine (NLA), inhibitor of NO synthase, on ET-1 content
      in cerebrospinal fluid (CSF) and on the vascular system was investigated in
      global ischemia/reperfusion of Mongolian gerbils. The results indicate that NLA
      induced a prolonged (2-3-fold) increase of ET-1 concentration above that seen in
      the CSF of untreated animals during ischemia/reperfusion. Both the transient and
      prolonged rise of ET-1 content observed in the CSF coincided with the reduction
      in the cerebral blood flow seen in untreated and NLA-treated gerbils,
      respectively, at the time of reperfusion.

PMID- 7583212
TI  - Haloperidol and reduced haloperidol-induced exacerbation of the dystonia produced
      by the kappa opioid U50,488H in guinea-pigs is associated with inhibition of
      sigma binding sites: behavioural and autoradiographical studies.
AB  - A single dose of haloperidol and reduced haloperidol has been found to exacerbate
      the dystonic response produced by U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N
      [2-(1-pyrrolidinyl) -cyclohexyl]-benzeacetamide methane sulphonate) in guinea
      pigs [8]. The present study sought to correlate the behavioural effect of
      haloperidol and reduced haloperidol with their effect on inhibition of sigma
      binding sites in guinea-pig brain using receptor binding and semi-quantitative
      autoradiography. In the first experiments, groups of guinea-pigs were injected
      with saline (control, n = 12), haloperidol (0.1 and 1 mg/kg i.p., n = 5) or
      reduced haloperidol (0.1 and 1 mg/kg i.p., n = 5) 1, 3 and 10 days before,
      followed by U50,488H (10 mg/kg s.c.) and the effect on the dystonic response
      rated using a behavioural rating scale [8]. In the second experiments, animals (n
      = 5) were injected with saline, haloperidol and reduced haloperidol as above and
      killed 1, 3 and 10 days later, their brains removed, dissected and tissue
      sections processed for sigma binding site autoradiography using [3H]3-(3
      hydroxyphenyl)-N-(n-propyl)piperidine ([3H]-3-PPP). Triplicate tissue sections
      were wiped using GF/C filters and radioactivity counted. Injection of haloperidol
      and reduced haloperidol 1, 3 and 10 days earlier exacerbated the dystonic
      response by decreasing the latency to maximal dystonia and increasing the
      duration of the response at each dose tested compared with saline-treated
      animals. These effects of haloperidol and reduced haloperidol on latency and
      duration were time-related since the effect at 1 > 3 > 10 days. In addition, [3H]
      3-PPP binding was inhibited by haloperidol and reduced haloperidol in a dose-and
      time-related manner. For example, % inhibition of [3H]-3-PPP binding for
      haloperidol (1 mg/kg) > haloperidol (0.1 mg/kg) and % inhibition of binding (mean
      +/- SEM) produced by haloperidol (0.1 mg/kg) at 1 (96.1 +/- 2.4) > 3 (74.8 +/-
      4.8) > 10 days (36.2 +/- 1.6). Similar results were obtained for haloperidol (1
      mg/kg) and reduced haloperidol (0.1 and 1 mg/kg). [3H]-3-PPP autoradiography
      confirmed these binding data. The results indicate that the exacerbation by sigma
      ligands of the dystonia produced by U50,488H was associated with the degree of
      inhibition of [3H]-3-PPP binding.

PMID- 7583213
TI  - Calretinin-containing preganglionic nerve terminals in the rat superior cervical
      ganglion surround neurons projecting to the submandibular salivary gland.
AB  - The distribution and targets of calretinin-immunoreactive preganglionic nerve
      terminals in the superior cervical ganglion of the rat were examined using
      immunohistochemistry and retrograde neuronal tracing. Calretinin-immunoreactive
      nerve terminals were found throughout the ganglion, forming distinct pericellular
      baskets around a sub-population of postganglionic neurons. The targets of
      postganglionic neurons surrounded by calretinin-immunoreactive nerve terminals
      were determined after injection of tracer into the submandibular salivary gland,
      the extra-orbital lacrimal gland, the thyroid gland, the anterior chamber of the
      eye or the skin of the forehead. Only when tracer was injected into the
      submandibular gland were neurons labelled that were surrounded by calretinin
      immunoreactive nerve terminals. When immunohistochemistry using antisera to
      neuropeptide Y was combined with retrograde tracing, only submandibular gland
      projecting neurons lacking neuropeptide Y were surrounded by calretinin
      immunoreactive terminals. When retrograde neuronal tracer was injected into the
      superior cervical ganglion, a proportion of retrogradely-labelled neurons in the
      upper thoracic spinal cord showed relatively weak calretinin-immunoreactivity.
      All calretinin-immunoreactive terminals in the superior cervical ganglion
      disappeared following section of the sympathetic chain distal to the superior
      cervical ganglion. Thus, calretinin is present in a population of preganglionic
      neurons projecting exclusively to neuropeptide Y non-immunoreactive (presumably
      secretomotor) neurons innervating the submandibular salivary gland of the rat.

PMID- 7583214
TI  - Degradation of fodrin and MAP 2 after neonatal cerebral hypoxic-ischemia.
AB  - Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral
      occlusion of the common carotid artery + 7.70% O2 for 100 min) and allowed to
      recover for 3 h, 24 h, 2 days or 14 days. Consecutive tissue sections were
      stained with antibodies against alpha-fodrin, the 150 kDa breakdown product of
      alpha-fodrin (FBDP, marker of calpain proteolysis) or microtubule associated
      protein 2 (MAP 2, marker of dendrosomatic neuronal injury). Cortical tissue
      pieces were subjected to Western blotting using the antibody against the FBDP.
      Areas with brain injury displayed a distinct loss of MAP 2 which clearly
      delineated the infarct. FBDP accumulated in injured and borderline regions
      ipsilaterally and a less conspicuous, transient increase in FBDP also occurred in
      the contralateral hemisphere, especially in the white matter. A reciprocal
      staining pattern could be seen in the cerebral cortex, i.e. loss of MAP 2 and
      accumulation of FBDP, most pronounced 14 days after the insult. Fodrin and MAP 2
      are known calpain substrates, and degradation of these proteins preceded neuronal
      degeneration, indicating that these proteases may be involved in the early events
      triggering the cascades leading to neuronal death.

PMID- 7583216
TI  - Effects of dietary restriction on motor learning and cerebellar noradrenergic
      dysfunction in aged F344 rats.
AB  - Fisher 344 rats were fed either ad libitum or with a diet containing a 40%
      reduction of calories beginning at 4 months of age. At 14 months and 22 months
      male rats were tested for their ability to learn a complex motor skill. At both
      ages the diet restricted rats reached criterion of performing 10 successful
      crosses in 10 min at an earlier time than ad libitum fed controls. At 22 months
      of age the diet restricted rats showed improved acquisition of running times for
      the task. Male rats at 14 and 22 months and female rats at 24 months were
      examined electrophysiologically for the ability of isoproterenol to augment the
      action of GABA in the cerebellum when both substances were applied
      iontophoretically from an extracellular multibarreled glass electrode. In all 3
      age and sex groups there was an improvement in the beta-adrenergic receptor
      modulation of GABA responses in the dietary restricted vs. ad libitum rats.
      However, no difference was observed between dietary restricted and ad libitum
      rats when the number and affinity of cerebellar beta-adrenergic receptors was
      assessed with 125I-iodopindolol binding. Overall, there was a significant
      improvement in cerebellar noradrenergic function in the dietary restricted rats
      and this was accompanied by an improvement in motor learning.

PMID- 7583215
TI  - Fodrin degradation and subcellular distribution of calpains after neonatal rat
      cerebral hypoxic-ischemia.
AB  - Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral
      occlusion of the common carotid artery + 7.70% O2 for 100 min). Ipsi-and
      contralateral parietal cerebral cortex was assayed with Western blotting for
      fodrin breakdown product (FBDP). Calpain immunoreactivity was assayed in the
      cytosolic fraction (CF) and the membrane and microsomal fraction (MMF). Calpain
      immunoreactivity decreased bilaterally in the CF during the insult (62-68% of
      controls) and remained significantly lower during early recovery, whereas the MMF
      showed no significant changes. This relative redistribution of calpains coincided
      with the appearance of FBDP in the left, ipsilateral hemisphere, displaying a
      significantly higher level of FBDP from immediately after the insult until at
      least 1 day of recovery (204-292% of controls). No significant changes in FBDP
      could be detected in the right, contralateral hemisphere, indicating that
      although redistribution of calpains occurred, hypoxia per se did not suffice to
      initiate fodrin degradation in this model of neonatal hypoxic-ischemia.

PMID- 7583217
TI  - Increased vasopressor actions of intraventricular neuropeptide Y-(13-36) in
      spontaneously hypertensive versus normotensive Wistar-Kyoto rats. Possible
      relationship to increases in Y2 receptor binding in the nucleus tractus
      solitarius.
AB  - The C-terminal NPY fragment (13-36)[NPY-(13-36)], a Y2 receptor agonist, elicits
      vasopressor responses upon central administration. The cardiovascular responses
      of NPY-(13-36) together with the distribution of NPY receptor subtypes within the
      nucleus tractus solitarius (nTS) have therefore been studied in spontaneously
      hypertensive rats (SHR). NPY-(13-36) was injected intracerebro-ventricularly in
      different doses (7.5 to 3000 pmol) in awake, unrestrained rats to evaluate the
      cardiovascular effects. NPY receptor subtypes were studied by autoradiography
      using [125I]peptide YY ([125I]PYY) as a radioligand and by masking the NPY Y1 and
      Y2 receptor subtypes with unlabelled [Leu31,Pro43]NPY and NPY-(13-36)
      respectively. In both male SHR and age-matched male normotensive Wistar-Kyoto
      rats (WKY) NPY-(13-36) injections elicited vasopressor effects. In WKY this
      effect was dose-dependent and became significant at doses from 75 pmol, whereas
      in the SHR the vasopressor effect had a longer duration than in the WKY and
      became significant at lower doses (25 pmol) but associated with the development
      of an early ceiling effect. The heart rate was unaffected in both groups of rats.
      Total specific [125I]PYY binding in the nTS was 25% higher in SHR than in WKY
      rats. By masking the Y1 and Y2 receptor subtypes respectively it could be shown
      that this difference was due to an increase in Y2 receptor binding within the
      nTS. The present results give evidence for an increased potency but not an
      increased efficacy of NPY-(13-36) in inducing a pressor response in the SHR
      associated with a longer duration as compared with the WKY rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7583218
TI  - Indirect potentiation of synaptic transmission by metabotropic glutamate
      receptors in the rat hippocampal slice.
AB  - The role that the metabotropic glutamate receptor plays in synaptic transmission
      is complex due to the multiple subtypes involved, which initiate a number of
      intracellular mechanisms. Here we have investigated the role of the metabotropic
      glutamate receptor in the induction of long-term potentiation (LTP). We have
      shown that, providing the CA3 region remains attached to the slice, it is
      possible to induce potentiation by bath perfusion of the metabotropic receptor
      agonist (1S,3R) 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) alone. The
      extent of the potentiation observed showed a strong negative correlation with the
      age of the animal from which the slices were prepared. Perfusion of ACPD was
      associated with an increase in the excitability of antidromically activated CA3
      neurones, the appearance of spontaneous burst firing within the CA3 region, and
      an increased fibre volley recorded in the CA1 region. Blockade of N-methyl-D
      aspartate (NMDA) receptors prevented all these effects. We suggest that the ACPD
      induced potentiation of CA1 fEPSPs is an indirect effect caused by spontaneous
      burst firing and/or increased excitatory drive from CA3 neurones.

PMID- 7583219
TI  - Impulse-dependent and tetrodotoxin-sensitive release of GABA in the rat's
      substantia nigra measured by microdialysis.
AB  - gamma-Aminobutyric acid (GABA) release in the rat substantia nigra pars
      reticulata (SNR) was studied by microdialysis coupled with high-performance
      liquid chromatography and fluorimetric detection. Electrical stimulation of
      striatonigral axons in the internal capsule (IC) increased nigral GABA release in
      conscious and halothane-anaesthetized rats. This was prevented by intranigral
      infusion of tetrodotoxin (TTX) while basal GABA release was unaffected. Calcium
      free, cobalt-containing (2 mM CoCl2) artificial cerebrospinal fluid reduced basal
      GABA overflow but not that evoked with high K+ (100 mM). Extracellular levels of
      glutamate (GLU) and taurine (TAU) were not modified by IC stimulation, TTX or 0
      Ca2+ although high K+ promoted GABA and TAU release but not that of GLU. These
      data demonstrate an impulse-and sodium-dependent release of GABA from nigral
      afferent neurones which contribute little to the extracellular concentration of
      GABA under steady-state conditions.

PMID- 7583220
TI  - Anisomycin induces phase shifts of circadian pacemaker in primary cultures of rat
      suprachiasmatic nucleus.
AB  - We have developed a cell culture system for the rat suprachiasmatic nucleus, in
      which a clear circadian oscillation of vasopressin release was observed. Using
      this culture system, the effect of anisomycin, an inhibitor of protein synthesis,
      on the circadian rhythm was studied. A phase-delay of more than 15 h could be
      produced by a 6-h anisomycin pulse. The magnitude of the phase-shift was
      dependent on the circadian time of the drug treatment and on its dose. The phase
      response curve was similar to the response curves that have been measured for
      protein synthesis inhibitors in other organisms. These results strongly suggest
      that protein synthesis may be involved in the generation of circadian rhythms in
      mammals.

PMID- 7583221
TI  - Immunoelectron microscopy of beta-endorphinergic synaptic innervation of nitric
      oxide synthase immunoreactive neurons in the dorsal raphe nucleus.
AB  - On the basis of the comparing of the distribution of beta-endorphin-like
      immunoreactive neuronal fibres and nitric oxide synthase-like immunoreactive
      neurons in the dorsal raphe nucleus, the synapses between the two
      immunocytochemically identified neurons were studied with a modified DAB-silver
      gold intensification double immunostaining technique at the electron microscopic
      level. Although both of them can be found in the mediodorsal and medioventral
      parts of the dorsal raphe nucleus, the synapses between them could only be found
      in the mediodorsal part. The majority of the beta-endorphin-like immunoreactive
      neuronal fibers contained many dense-cored vesicles. The synapses made by beta
      endorphin-like immunoreactive neuronal axon terminals on nitric oxide synthase
      like immunoreactive neurons were both symmetrical and asymmetrical with the
      former predominant, especially in the axo-dendritic ones. beta-Endorphin-like
      immunoreactive perikarya could only be found in the ventrobasal hypothalamus.
      These findings suggest the possibility that the beta-endorphin- producing neurons
      in the ventrobasal hypothalamus could influence nitric oxide synthase-containing
      neurons in the dorsal raphe nucleus by synaptic relations.

PMID- 7583222
TI  - Reciprocal photolabile O2 consumption and chemoreceptor excitation by carbon
      monoxide in the cat carotid body: evidence for cytochrome a3 as the primary O2
      sensor.
AB  - High carbon monoxide (CO) gas tensions (> 500 Torr) at normoxic PO2 (125-140
      Torr) stimulates carotid chemosensory discharge in the perfused carotid body (CB)
      in the absence but not in the presence of light. According to a metabolic
      hypothesis of O2 chemoreception, the increased chemosensory discharge should
      correspond to a photoreversible decrease of O2 consumption, unlike a non
      respiratory hypothesis. We tested the respiratory vs. non-respiratory hypotheses
      of O2 chemoreception in the cat CB by measuring the effect of high CO.
      Experiments were conducted using CBs perfused and superfused in vitro with high
      CO in normoxic, normocapnic cell-free CO2-HCO3- buffer solution at 37 degrees C.
      Simultaneous measurements of the rate of O2 disappearance with recessed PO2
      microelectrodes and chemosensory discharge were made after flow interruption with
      and without CO in the perfusate. The control O2 disappearance rate without CO was
      -3.66 +/- 0.43 (S.E.) Torr/s (100 measurements in 12 cat CBs). In the dark, high
      CO reduced the O2 disappearance rate to -2.35 +/- 0.33 Torr/s, or 64.2 +/- 9.0%
      of control (P < 0.005, 34 measurements). High CO was excitatory in the dark, with
      an increase in baseline neural discharge from 129.2 +/- 47.0 to 399.3 +/- 49.1
      impulses per s (P < 0.0001), and maximum discharge rate of 659 +/- 76 impulses/s
      (N.S. compared to control) during flow interruption. During perfusion with high
      CO in the light, there were no significant differences in baseline neural
      discharge or in the maximum neural discharge after flow interruption, and little
      effect on O2 metabolism (88.8 +/- 11.5% of control, N.S., 29
      measurements).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583224
TI  - Increase in the calcium level following anodal polarization in the rat brain.
AB  - The accumulation of calcium ions (Ca) was examined in the rat brain by means of
      45Ca autoradiography following the application of a weak anodal direct current to
      the surface of the sensorimotor cortex. Repetition of the anodal polarization
      with 3.0 microA for 30 min caused more Ca to accumulate in the cerebral cortex.
      The degree and extent of accumulation was greater in the hemisphere ipsilateral
      to the polarization than in the other. Accumulation was also noted in the
      hippocampus and thalamus. Ca accumulation was detected after 24 h and it remained
      virtually constant up to 72 h after the last polarization. The results suggest
      that a long-lasting disturbance of Ca homeostasis is involved in the cortical
      plastic changes seen following anodal polarization.

PMID- 7583225
TI  - Long-term increases in synaptic density in chick CNS after passive avoidance
      training are blocked by an inhibitor of protein synthesis.
AB  - Long-term increases in synaptic density (first recorded 24 h after training of
      chicks on a one-trial passive avoidance task, and still present 48 h post
      training), are found bilaterally in a part of the striatum, the lobus
      parolfactorius (LPO) [23,36], and are believed to reflect a trace of long-term
      memory formation. Such increases in synaptic density are most likely to occur by
      either de novo synthesis of new synaptic material, or via post-translational
      modification of pre-existing components. Several previous studies have shown that
      inhibitors of protein synthesis such as anisomycin injected just before, or after
      training, can prevent long-term memory formation in the chick. The present study
      therefore examined whether the long-term increases in synaptic density in the LPO
      that occur after passive avoidance training can be blocked by anisomycin. Our
      data show clearly that chicks injected with anisomycin 30 min pre-training were
      amnesic on testing 24 h later, and the bilateral increases in synaptic density
      (of spine and shaft synapses) seen in saline injected trained controls, were
      significantly reduced, demonstrating that protein synthesis de novo is involved
      in the post-training increase in synaptic density in the LPO.

PMID- 7583223
TI  - The effect of hippocampal sympathetic ingrowth and cholinergic denervation on
      hippocampal M2 cholinergic receptors.
AB  - After cholinergic denervation of the hippocampus, via medial septal (MS) lesions,
      peripheral sympathetic fibers, originating from the superior cervical ganglia,
      grow into the hippocampus. In this study, we sought to determine the effect of
      hippocampal sympathetic ingrowth (HSI) on the M2 subtype of muscarinic
      cholinergic receptors, by examining the membrane binding of [3H]AF-DX 384 in
      hippocampal tissue from control rats, rats with HSI and rats with MS lesions +
      concurrent ganglionectomy (CD group). In dorsal hippocampus, Kd was found to be
      increased while Bmax was decreased in the CD group as compared with both the HSI
      and control group which did not differ from one another. In ventral hippocampus,
      Kd was found to be increased while Bmax was decreased in the CD group when
      compared only with the control group. These results suggest that sympathetic
      ingrowth, which has its greatest concentration in dorsal hippocampus, can
      'normalize' the M2 receptor in hippocampus.

PMID- 7583230
TI  - Synergism between diltiazem and MK-801 but not APV in protecting hippocampal
      slices against hypoxic damage.
AB  - In the present study, we investigated the possibility that MK-801 (dizocilpine),
      a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, owes its potent
      neuroprotective properties to calcium channel blocking ability rather than to its
      NMDA receptor antagonism. Rat hippocampal slices were exposed to a long hypoxic
      period (20 min) from which only 13.8% recovered their neuronal function after 30
      min of reoxygenation. The recovery rate of neuronal function from 20-min hypoxia
      was increased to 100% when slices were pretreated with 5 microM MK-801. DL-2
      amino-5-phosphonovalerate (APV), a competitive NMDA receptor antagonist, even at
      relatively high concentration (100 microM), provided only marginal protection
      against such severe hypoxic insult. The L-type calcium channel blocker diltiazem
      (DILT) was more effective than APV in protecting hypoxic slices against neuronal
      damage. Combining suboptimal concentrations of DILT and MK-801 produced a
      neuroprotective effect with significantly exceeded the calculated additive effect
      of the two drugs. Such synergism could not be demonstrated between DILT and APV,
      a combination that produced only the expected additive neuroprotective effect.
      The observed synergy between the calcium channel blocker (DILT) and MK-801, along
      with other studies that demonstrated interaction between these two drugs, led us
      to postulate that MK-801 possesses calcium channel blocking properties through
      which its neuroprotective effect is exerted. These calcium channels could either
      be of the L-type or otherwise, channels which are being activated only under
      stressful conditions, such as hypoxia or ischemia.

PMID- 7583228
TI  - Cholecystokinin octapeptide and the D2 antagonist raclopride induce Fos-like
      immunoreactivity in the shell part of the rat nucleus accumbens via different
      mechanisms.
AB  - Induction of neuronal Fos-like immunoreactivity (IR) in the rat brain by
      cholecystokinin octapeptide (CCK-8) and the dopamine (DA) D2 receptor antagonist
      raclopride was demonstrated. In vivo treatment with the CCK-8 (0.01, 0.1 and 1
      nmol/rat, i.c.v.) or the D2 antagonist raclopride (0.1, 0.5 and 1 mg/kg, i.p.)
      alone increased in a dose-dependent way the Fos-like ir profiles in the shell
      part of the rat nucleus accumbens (AcbSh). Combined treatment with CCK-8 (0.1
      nmol/rat) and raclopride (0.5 mg/kg) caused significant additive increases in the
      Fos-like ir profiles in the AcbSh. In the central caudate-putamen, the medial
      olfactory tubercle, and the frontal cerebral cortex where either compound alone
      was weakly active or inactive, the combined treatment with both compounds led to
      a significant induction of neuronal Fos-like ir profiles. These results suggest
      that the blockade of D2 and activation of CCK transduction lines can induce Fos
      like IR via different mechanisms. They may produce additive effects in AcbSh and
      synergistic effects in the caudate-putamen and the olfactory tubercle on the
      induction of neuronal Fos-like IR and thus on long-term regulation of gene
      expression in the striatum.

PMID- 7583226
TI  - Localization and possible interactions of catecholamine-and NADPH-diaphorase
      neurons in human medullary autonomic regions.
AB  - The human medulla contains catecholamine-and NADPH-diaphorase (NADPH-d) neurons
      in both the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS).
      There is abundant experimental evidence for the critical role of these areas in
      control of arterial pressure. We sought to determine the pattern of distribution
      and topographic relationship between tyrosine hydroxylase (TH)-immunoreactive and
      NADPH-d-reactive cell groups in normal human VLM and NTS, in view of their
      potential implications in human autonomic control and involvement in central
      autonomic disorders. Medullae from three patients with no neurologic disease were
      obtained at autopsy within 24 h of death. Individual sections, obtained from the
      rostral and caudal medulla, were stained for TH, NADPH-d or both. We found that:
      (1) TH-and NADPH-d positive neurons are topographically segregated in the VLM;
      (2) in the VLM, TH and NADPH-d neurons may coexist within a given area but both
      markers do not appear to coexist in single neuron; (3) NADPH-d-reactive fibers
      and processes overlap the distribution of TH neurons within the VLM; and (4) both
      TH-and NADPH-d-reactive processes appear to innervate intrinsic blood vessels in
      the VLM and NTS. Thus, there are important topographic relationships between
      catecholamine and NO-synthesizing neurons in human VLM and perhaps NTS, including
      innervation of intrinsic blood vessels. This may have important implications in
      regulation of autonomic reflexes, sympathetic excitatory drive and intrinsic
      control of cerebral blood flow in humans.

PMID- 7583229
TI  - Evidence for a human spinal stepping generator.
AB  - Flexion reflexes elicited by surface stimulation in spinal cord-injured man have
      been used to provide limb flexion in gait restoration. In this study, the pattern
      of the flexion reflexes observed in one subject supports the theory that a spinal
      stepping generator exists in man.

PMID- 7583227
TI  - Intrastriatal injections of the succinate dehydrogenase inhibitor, malonate,
      cause a rise in extracellular amino acids that is blocked by MK-801.
AB  - The effects of intrastriatal injections of a reversible inhibitor of succinate
      dehydrogenase, malonate, on the extracellular concentrations of amino acid
      neurotransmitters were examined using a microdialysis probe that was positioned a
      fixed distance from an injection cannula. Malonate (2 mumol) caused a 23 +/- 5
      fold increase in extracellular glutamate (Glu), a 18 +/- 6-fold increase
      extracellular gamma-aminobutyric acid (GABA) and a modest increase in
      extracellular aspartate (Asp, 2.9 +/- 0.8-fold increase). Administration of the
      NMDA receptor antagonist MK-801 (5 mg/kg) prior to injection of malonate almost
      completely blocked these increases. This study provides direct evidence that
      inhibition of succinate dehydrogenase causes an increase in extracellular amino
      acid neurotransmitters and further evidence that bioenergetic defects may
      contribute to the pathogenesis of chronic neurodegenerative diseases through an
      excitotoxic mechanism.

PMID- 7583233
TI  - 45Ca accumulation in rat brain after closed head injury; attenuation by the novel
      neuroprotective agent HU-211.
AB  - 45Ca accumulation was studied autoradiographically as a marker for lethally
      injured brain tissue following closed head injury (CHI), and applied to an
      investigation of the neuroprotective effect of the non-psychoactive cannabinoid
      (+)-(3S,4S)-7-hydroxy-D-6 tetrahydro-cannabinol 1,1-dimethylheptyl (HU-211).
      Amassment of 45Ca in rat brain was examined 24 or 72 h after induction of CHI in
      the left hemisphere by a weight-drop device. Concentration of 45Ca within 15
      different brain regions was assessed by relative optical density. There was
      increased 45Ca accumulation in the hemisphere ipsilateral to the side of the
      insult as compared with the contralateral hemisphere. The highest density of
      radioactive labeling was found in the anterior cortex and in the frontal parts of
      the parietal cortex, with accumulation expanding as a function of time post
      injury. On the third day following trauma the amount of accumulated 45Ca was
      higher than that at 24 h after CHI, with more distant 45Ca-accumulating
      structures involved: the ventral posterolateral nucleus of the thalamus and the
      substantia nigra. Histological examination revealed necrotic tissue in the
      regions accumulating 45Ca. HU-211, a stereoselective inhibitor of the N-methyl-D
      aspartate (NMDA) receptor, was injected immediately after induction of trauma.
      One day after trauma, HU-211 had significantly decreased both the volume of the
      45Ca accumulating zone and the concentration of the amassed radioisotope. In the
      HU-211 treated rats a considerable reduction in radioactive labeling was also
      found 72 h after trauma. The ability of HU-211 to decrease 45Ca accumulation
      after head trauma is probably due to its ability to attenuate Ca2+ fluxes through
      the NMDA receptor-mediated calcium channels and to reduce the depolarization
      evoked Ca2+ fluxes. On the basis of our results, HU-211 seems to be a promising
      therapeutic agent for head trauma in humans.

PMID- 7583232
TI  - Increased polyamine levels and changes in the sensitivity to convulsions during
      chronic treatment with cocaine in mice.
AB  - Polyamines have been demonstrated to modulate seizure activity in animals.
      Repeated administration of a subthreshold dose of cocaine resulted in the
      development of sensitization to cocaine-induced seizures during an initial 3 or 4
      days, followed by the development of tolerance to seizures on days 5 and 6. In
      the present study, polyamines, such as putrescine, spermidine and spermine, were
      measured in regions of the brain obtained from mice that showed differential
      sensitivity in seizure activity during repeated cocaine injections. Animals were
      sacrificed for polyamine measurements 24 h after the second and the fifth
      injections of either cocaine or saline (on day 3 and day 6, respectively), and 3
      days after the last injection. On day 3, there were significant increases in
      putrescine in the striatum, hippocampus and cerebellum, and in spermine in the
      cerebellum of cocaine-treated mice, as compared to saline-treated mice. On day 6,
      treatment with cocaine significantly increased putrescine in all regions, and
      spermidine in striatum and hippocampus, as compared to saline treatment. Cocaine
      treatment had no effect on any polyamine levels measured 3 days after the last
      injection, except for spermidine in the cortex. Because putrescine has been shown
      to be an antagonist of the polyamine-binding site on the N-methyl-D-aspartate
      receptor and to retard the development of amygdala-kindling, the present results
      suggest that the increases in putrescine content may be associated with the
      development of tolerance to convulsant effects observed during the later period
      of repeated administration of cocaine.

PMID- 7583231
TI  - Intrahippocampal administration of (+)-SKF 10,047, a sigma ligand, reverses MK
      801-induced impairment of working memory in rats.
AB  - In order to clarify the roles of the hippocampal sigma site and phencyclidine
      (PCP) binding site on the NMDA receptor/channel complex in the regulation of
      working memory in rats, the effects of intrahippocampal administration of ligands
      for both binding sites on this behavior were examined with a three-panel runway
      task. MK-801, a potent noncompetitive NMDA antagonist with high affinity for the
      PCP site, significantly increased the number of working memory errors (attempts
      to pass through two incorrect panels of the three panel-gates at four choice
      points), when injected bilaterally at 0.1 and 0.18 microgram/side into the dorsal
      hippocampus. However, intrahippocampal injection of (+)-SKF 10,047, a sigma
      ligand, at doses up to 1.0 microgram/side had no significant effect on the number
      of working memory errors. The working memory impairment induced by
      intrahippocampal MK-801 (0.18 microgram/side) was attenuated by concurrent
      injection of 1.0 microgram/side (+)-SKF 10,047, but not by that of 1.0
      microgram/side (-)-SKF 10,047. These results suggest that activation of
      hippocampal sigma and PCP binding sites exerts antagonistic effects on working
      memory function, possibly through modulation of NMDA receptor-mediated
      glutamatergic neurotransmission.

PMID- 7583235
TI  - Glycine-induced CA1 excitotoxicity in the rat hippocampal slice.
AB  - We evaluated the effects of glycine exposure upon CA1 evoked response in the rat
      hippocampal slice. Exposure to 10 mM glycine for 16 min, produced rapid neuronal
      firing and increased orthodromic population spike (PS), followed by loss of CA1
      neural transmission. Upon recovery, CA1 orthodromic and antidromic PS regained a
      mean of only 12 +/- 6% and 8 +/- 5% of initial amplitude. The
      electrophysiological pattern of glycine injury was similar to the excitotoxic
      damage produced by 8 min exposure to sodium glutamate 9 mM. L-Histidine, an
      inhibitor of glycine transport, exacerbated glycine-induced injury, just as
      dihydrokainic acid, a glutamate transport inhibitor, exacerbated glutamate
      induced injury. The anticonvulsant felbamate (1.3 mM), as well as 100 microM zinc
      chloride, provided excellent protection from glycine-induced injury. 7
      Chlorokynurenic acid appeared to be toxic. Blockers of the NMDA-associated ionic
      channel and methyl arginine, prevented loss of neural transmission, but did not
      prevent accompanying hyperexcitability. Only 10 mM magnesium sulfate provided
      full protection against 9 mM glutamate exposure. Perfusion with low calcium ACSF
      protected against both glycine and glutamate-induced injury. Thus, exposure to
      glycine resembled the excitotoxic effects of glutamate, but showed a different
      profile of protection. These results suggest that glycine elevations as occur
      under physiologic and pathologic conditions may modulate neuronal activity.

PMID- 7583234
TI  - Distinction between binding of [3H]triamcinolone acetonide to a ligand binding
      domain on the glucocorticoid receptor complex in cytosol fractions of brain and
      liver from the rat with intact adrenals.
AB  - Binding of [3H]triamcinolone acetonide (TA) was examined to evaluate possible
      differences in biochemical and pharmacological profiles of a ligand binding
      domain on the naive glucocorticoid (GC) receptor complex between cytosol
      fractions of brain and liver obtained from the rat with intact adrenals.
      Unlabeled TA was 3-times less potent in displacing [3H]TA binding at equilibrium
      in the presence of Na2MoO4 at 2 degrees C in brain than in liver, while
      dexamethasone was more than 15-times more potent in displacing brain binding than
      liver binding. Both progesterone and aldosterone caused more than 20-times more
      potent displacement of [3H]TA binding in brain than in liver. However, zinc ions
      were effective in similarly inhibiting binding at equilibrium via lowering the
      affinity without affecting the density. In contrast to these experiments done at
      2 degrees C, the addition of Na2MoO4 potentiated binding in brain and liver in a
      transient manner at 30 degrees C. Prolongation of incubation period from 30 min
      to 5 h induced a rightward shift of concentration-response curves of Na2MoO4 for
      [3H]TA binding at 30 degrees C in brain and liver in an irreversible fashion. The
      potentiation by Na2MoO4 was prevented by the addition of leupeptin but not 5
      other protease inhibitors in brain cytosol fractions. Ion exchange chromatography
      revealed that elution profiles were entirely different from each other for [3H]TA
      binding between brain and liver cytosol fractions. These results suggest that GC
      receptors may respond to a variety of signals mediated by different steroid
      hormones through broader pharmacological spectrum of the ligand binding domain in
      brain than in liver.

PMID- 7583239
TI  - Differential testicular responses to short daylength in deer mice are reflected
      by regional and morphological differences in the GnRH neuronal system.
AB  - Male deer mice (Peromyscus maniculatus) respond to short photoperiod with a range
      of spermatogenic responses. About one-third of all short day exposed mice exhibit
      a complete cessation of spermatogenesis (reproductive responsive), while about an
      equal number remain reproductively competent (reproductive nonresponsive). These
      differential spermatogenic responses are mirrored by endocrine measures;
      reproductive responsive males exhibit reduced circulating levels of testosterone
      and luteinizing hormone, while reproductive nonresponsive males exhibit long day
      levels of both hormones. A variety of evidence indicates that despite individual
      differences in reproductive responses, all short day exposed mice detect and
      respond to the change in photoperiod at the level of the hypothalamus,
      irrespective of gonadal response. We investigated whether deer mice exhibiting
      disparate gonadal responses to short days differed in aspects of the GnRH
      neuronal system, as revealed by immunocytochemistry. Reproductively mature males
      were maintained on either long (16L:8D) or short (8L:16D) photoperiod for 8
      weeks. Thereafter, regional and morphological differences in GnRH-containing
      neurons were compared among long day (n = 8) and short day reproductive
      responsive (n = 8) and nonresponsive (n = 8) deer mice. Results demonstrate both
      an effect of photoperiod and reproductive state on the number, location and
      morphology of immunoreactive-GnRH neurons. Short days caused immunoreactive GnRH
      cell number to increase in both short day phenotypes relative to long day mice.
      Significant differences among treatment groups in the numbers of cells per region
      were confined to the lateral hypothalamus and lateral preoptic area. Both short
      day phenotypes exhibited an increase in cell number in the lateral preoptic area,
      compared to long day mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583237
TI  - LIF-and IL-1 beta-mediated increases in substance P receptor mRNA in axotomized,
      explanted or dissociated sympathetic ganglia.
AB  - Regulation of substance P receptor (SPR) mRNA was examined in the rat sympathetic
      superior cervical ganglion (SCG) in vitro and in vivo after axotomy. Interleukin
      1 beta (IL-1 beta) treatment of explanted ganglia elevated levels of SPR mRNA. By
      contrast, dissociated cultures of purified sympathetic neurons, purified
      fibroblasts, and purified Schwann cells each expressed only low levels of SPR
      mRNA, and treatment with the cytokine did not alter levels of the receptor mRNA.
      Treatment of Schwann cell or fibroblast cultures with leukemia inhibitory factor
      (LIF) also did not alter SPR mRNA. However, treatment of pure neuronal cultures
      with LIF significantly elevated levels of the receptor mRNA. Further, SPR mRNA
      increased in pure sympathetic neurons cultured in the presence of conditioned
      medium from IL-1 beta treated fibroblasts or Schwann cells; this effect was
      blocked in the presence of LIF antibody. This suggests that the stimulatory
      effects of IL-1 beta on SPR mRNA in explants is mediated by LIF release. Axotomy
      of the SCG in vivo resulted in a significant increase in LIF mRNA. Further,
      axotomy resulted in a significant increase in SPR mRNA, suggesting that LIF may
      mediate the increase in SPR mRNA. In view of the known effects of substance P
      (SP) on inflammatory responses, these observations suggest that coordinated
      expression of SP and SPR mRNA in neurons after nerve injury may participate in
      inflammatory and repair processes in the ganglion.

PMID- 7583238
TI  - Effects of streptozotocin-induced diabetes on prodynorphin-derived peptides in
      rat brain regions.
AB  - Pharmacological studies suggest that diabetes produces changes in the brain
      opioid system, affecting several behavioral functions including analgesia,
      feeding and self-stimulation. Previous investigations of opioid receptor binding
      have failed to explain the unusual opioid pharmacology of the diabetic animal. In
      the present study, the effects of streptozotocin-induced diabetes on levels of
      three immunoreactive (ir)-prodynorphin-derived peptides, ir-dynorphin A1-17 (A1
      17), ir-dynorphin A1-8 (A1-8) and ir-dynorphin B1-13 (B1-13), were determined in
      eleven brain regions known to be involved in appetite, taste and reward. Diabetes
      was found to increase levels of A1-17 in the ventromedial and dorsomedial
      hypothalamic nuclei (+60% and +25%, respectively) and levels of A1-8 in the
      dorsomedial and lateral hypothalamus (+45% and +35%, respectively). The possible
      significance of these results is discussed in relation to (i) diabetic
      hyperphagia, (ii) medial hypothalamic transduction of circulating insulin levels,
      and (iii) the potentiation of reward by metabolic need states.

PMID- 7583236
TI  - Effects of selective dopamine depletion in medial prefrontal cortex on basal and
      evoked extracellular dopamine in neostriatum.
AB  - In this study, we demonstrate that 6-hydroxydopamine (6-OHDA) can be used to
      produce a lesion of dopamine (DA) terminals in medial prefrontal cortex (mPFC)
      while sparing the noradrenergic innervation in this region. Furthermore, we
      determined the impact of these lesions on both extracellular DA in neostriatum,
      using in vivo microdialysis, and locomotor activity. Our results demonstrate
      that, whereas higher doses of 6-OHDA (> or = 4 micrograms) depleted both DA and
      norepinephrine (NE) in mPFC, 1 micrograms 6-OHDA produced a depletion of DA (
      79%) without significantly affecting NE content (-13%). Selective depletion of DA
      content in mPFC did not alter basal levels of extracellular DA in neostriatum
      determined 14 days after the lesion. The lesion also did not alter the ability of
      acute tail pressure (30 min) to increase extracellular DA in neostriatum or to
      stimulate locomotor activity. Depletion of DA in mPFC did not alter the ability
      of d-amphetamine (1.5 mg/kg, i.p.) to increase intracellular DA in neostriatum.
      In contrast, the maximum amphetamine-induced increase in locomotor activity was
      attenuated in lesioned rats as compared with control rats (670 and 280 locomotor
      counts/15 min, respectively). These data suggest that in the intact system, DA
      terminals in mPFC do not regulate extracellular DA in neostriatum. In addition,
      these data confirm that DA terminals in mPFC can influence stimulant-induced
      locomotion.

PMID- 7583240
TI  - Sleep deprivation differentially alters the mRNA and protein levels of
      neurogranin in rat brain.
AB  - The mRNA level of the 17-kDa protein neurogranin (NG), a postsynaptic substrate
      of the protein kinase C, has previously been found to be decreased in rat
      forebrain after 24-h sleep deprivation (SD). To investigate the functional
      significance of this finding in various forebrain regions, the effect of 24-h SD
      on the mRNA level and the protein level of NG was determined in the cerebral
      cortex, hippocampus, and the total of the remaining subcortical forebrain plus
      midbrain areas (SFMA) of rats. In these areas, high levels of both NG mRNA and NG
      protein were detected by in situ hybridization and immunohistochemistry,
      respectively. NG protein was recognized in brain tissue by newly developed
      polyclonal antibodies. As determined by RNase protection assays, the level of NG
      mRNA was decreased in SFMA by 34 +/- 7% (P < 0.05) after 24-h SD, and was not
      significantly affected in the cerebral cortex and hippocampus. In contrast, on
      Western blots, the protein concentration of NG was reduced in the cerebral cortex
      by 37 +/- 7% (P < 0.05) whereas no significant changes were present in other
      brain areas tested. The results indicate that the mRNA and protein levels of NG
      are differentially modulated in rat brain by the prolongation of the waking
      period.

PMID- 7583241
TI  - Quantitation of Alzheimer's amyloid peptide and identification of related amyloid
      proteins by dot-blot immunoassay.
AB  - In Alzheimer's disease, the main component of amyloid deposits is a 39-43 amino
      acid peptide referred to as amyloid peptide or A beta. A crucial issue in the
      study of this disorder is to define the sequence of events that lead to amyloid
      deposition. In the present study, a new approach was developed that allows to
      specifically solubilize A beta peptide trapped within amyloid deposits and to
      quantify its amount by dot-blot immunoassay. The present method also permits to
      isolate components tightly bound to A beta and that are likely to catalyze its
      aggregation. Biochemical A beta quantitation was performed in 4 Brodmann areas
      from 17 elderly individuals exhibiting different degrees of amyloidosis. In
      parallel, classical neuropathology was done by histochemical and
      immunohistochemical methods. A beta amounts (pmol) were correlated to the number
      of amyloid deposits determined by neuropathology showing high statistical
      significance. Moreover, amyloid-binding proteins including apolipoprotein E and
      heparan sulfate proteoglycans were also found associated to A beta in the amyloid
      preparation. The present biochemical procedure is a new and reliable method to
      quantify amyloid deposition in brain. Furthermore, it allows to detect amyloid
      associated components such as apolipoprotein E, that may be involved in the
      pathological process of amyloidogenesis.

PMID- 7583242
TI  - Learning-specific, time-dependent increase in [3H]phorbol dibutyrate binding to
      protein kinase C in selected regions of the rat brain.
AB  - Several lines of evidence indicate that protein kinase C (PKC) participates in
      long-term potentiation (LTP) and in certain forms of learning. Here we describe a
      rapid, specific and time-dependent increase in [3H]phorbol-12,13-dibutyrate
      ([3H]PDBu) binding to membrane-associated PKC in selected brain regions of rats
      submitted to an inhibitory avoidance task. A quantitative film autoradiographic
      method was used to determine the amount and distribution of membrane-bound PKC in
      rats sacrificed at various time intervals after training. At 0, 30 and 120 min
      following training there was a prominent increase (up to 200%) in the binding of
      [3H]PDBu throughout the hippocampus relative to naive, shocked or habituated
      control groups. No significant changes in [3H]PDBu binding in any brain region
      were found at 180 min after training. Similar training-specific increments in the
      binding of [3H]PDBu were observed in the frontal, parietal and entorhinal
      cerebral cortices, amygdala and cerebellum. The maximal effect was seen at 30 min
      in the CA2 region of the hippocampus (+200%) and at 30 and 120 min after training
      in the amygdala (+170%) in comparison to naive control values. No alterations in
      [3H]PDBu binding were found in the other brain regions studied. The present
      findings, together with previous data reporting a similar temporal course in the
      effects of intrahippocampal or intraamygdala infusion of specific PKC inhibitors
      on memory, suggest that PKC activation plays a role in the acquisition and
      consolidation of an inhibitory avoidance learning.

PMID- 7583243
TI  - Modulation by inositol of cholinergic- and serotonergic-induced seizures in
      lithium-treated rats.
AB  - Hippocampal and cortical EEG recordings in rats were used to monitor the in vivo
      modulation by lithium of responses to agonists for 5HT2/5HT1c serotonergic (DOI)
      and cholinergic (pilocarpine) receptors and the influence of inositol
      administration. Administration of DOI (8 mg/kg) or pilocarpine (30 mg/kg) to rats
      pretreated with lithium acutely (3 mmol/kg) or chronically (dietary, 4 weeks)
      resulted in seizures, whereas these doses did not cause seizures without lithium
      pretreatment. This indicated that lithium most likely affects a signal
      transduction process common to both systems, which is the phosphoinositide second
      messenger system. To examine the potential influence of altered inositol levels
      on these responses, we tested the effects of infusions (10 mg, i.c.v.) of myo
      inositol, a precursor of phosphoinositide synthesis, and of epi-inositol, an
      isomer not used for phosphoinositide synthesis. Administration of myo-inositol
      (10 mg) slightly reduced the incidence of seizures induced by acute lithium plus
      DOI but almost completely blocked seizures induced by acute lithium plus
      pilocarpine. This was surprising since seizures induced by acute lithium plus DOI
      were less severe than those after acute lithium plus pilocarpine, but myo
      inositol was more effective in blocking the latter. Epi-inositol also blocked
      seizures under both conditions but it was less effective than myo-inositol after
      treatment with acute lithium plus pilocarpine. The latencies to seizures and/or
      severity of seizures were potentiated more by chronic than acute lithium
      pretreatment with both DOI and pilocarpine, but attenuation by myo-inositol was
      less with each agonist after chronic lithium compared with acute lithium
      treatment. Peripheral administration of a high dose of myo-inositol blocked
      seizures induced by acute lithium plus pilocarpine, but the inositol treatment
      itself was toxic and caused seizures prior to pilocarpine administration, so the
      mechanism of action cannot simply be attributed to increased brain inositol
      levels. These results demonstrate that lithium modulates the in vivo responses to
      DOI and pilocarpine, most probably through an effect on the phosphoinositide
      signal transduction system. They also show that centrally administered myo
      inositol modifies responses to these agents, but the effectiveness of epi
      inositol and other results leave unclear the mechanistic basis of its actions.

PMID- 7583244
TI  - Prenatal stress in rats facilitates amphetamine-induced sensitization and induces
      long-lasting changes in dopamine receptors in the nucleus accumbens.
AB  - Exposure of rats to restraint stress during late pregnancy produces offspring
      with a variety of behavioral and neurobiological alterations. It has been
      suggested that prenatal stress leads to long-lasting changes in the hypothalamo
      pituitary-adrenal axis in the offspring. One feature of prenatally-stressed rats
      is a susceptibility to amphetamine self-administration. Since this behavior has
      been related to amphetamine-induced sensitization and the activity of the
      mesolimbic dopamine system, we measured dopamine receptor densities and
      amphetamine-induced sensitization in these animals. The motor response to the
      first administration of amphetamine was similar in both prestressed and
      unstressed groups of adult animals, but after repeated drug injections,
      behavioral sensitization was observed sooner in the prenatally-stressed rats than
      in the controls. In separate groups of adult animals, densities of D1, D2 and D3
      dopamine receptor subtypes in the striatum and nucleus accumbens were measured in
      prenatally-stressed and control rats by quantitative autoradiography using
      [3H]SCH23390, [3H]sulpiride and [3H]7-OH-DPAT as ligands respectively. Prenatal
      stress was found to produce the following alterations in the adult offspring: (i)
      no significant change in D1 receptor binding in either striatum or nucleus
      accumbens; (ii) a significant (+24%) increase in D2 receptor binding in the
      nucleus accumbens; (iii) a significant decrease in D3 receptor binding in both
      the shell (-16%) and the core (-26%) of the nucleus accumbens. These observations
      indicate that prenatal stress induces long-lasting changes in the dopamine
      sensitivity of the nucleus accumbens and in the capacity to develop amphetamine
      induced sensitization in adulthood. The possible relationship between an impaired
      control of corticosterone secretion in prenatally-stressed animals and long-term
      changes in the mesolimbic dopamine system is discussed.

PMID- 7583245
TI  - Functional properties of regenerated optic axons terminating in the primary
      olfactory cortex.
AB  - When the optic nerve of Rana pipiens is cut and deflected into the telencephalon,
      the regenerating fibers terminate selectively in the superficial neuropil of the
      primary olfactory cortex. These redirected fibers and their terminals on the
      dendrites of the cortical cells appear normal by LM and EM criteria. Electrical
      recording, done 2-16 months after surgery, shows visually evoked activity in the
      superficial neuropil (Layer I) of the olfactory cortex, and visually excited
      responses in the deep cortical cell layer (Layer II). In the normal frog, the
      electrical activity seen in the neuropil of the olfactory cortex consists of
      small transients about 2-3 x the noise level of the electrode contact. These
      occur spontaneously and are also excited by puffs of air to the nose. There is no
      such excitation by visual stimuli. Larger initially negative spikes cell above
      noise level are recorded in the cell layer next to the ependymal surface, and
      these are also spontaneous, or excited by puffs of air to the nose, but not by
      visual stimuli. In the operated frog, the small transients in the neuropil appear
      and are excited by the puffs of air and by visual stimuli. Similarly the
      responses in the cell layer are excited by both sorts of stimuli. But new types
      of electrical signals appear in the neuropil; they are driven only by visual
      stimuli presented to the affected eye. These are very large transients of the
      kind found in the tectal neuropil and have the two characteristic shapes which
      were classified as B and C types in the tectum. Such large transients are never
      seen in the neuropil of the olfactory cortex in normal frogs. The receptive
      fields of the small visually driven transients in the neuropil are not easy to
      make out because the signal levels are so close to the noise level that different
      units cannot be reliably distinguished from each other. But the receptive fields
      of the much larger B and C type unit responses are as easy to classify and plot
      as they are in tectum, even though on the average they are only about 2/3 as
      large as in tectum. The single-unit receptive fields belong to one or another of
      the several types of retinal ganglion cell classes distinguished in optic-nerve
      recordings. Four of the major classes normally project to the tectum and a fifth
      projects to the lateral geniculate complex. But all five are present in the
      ectopic projection to the olfactory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7583246
TI  - Gonadotropin-releasing hormone neurons in the rhesus macaque are not
      immunoreactive for the estrogen receptor.
AB  - The issue of whether gonadotropin-releasing hormone (GnRH) neurons in the primate
      contain the estrogen receptor was examined by immunocytochemistry using
      prepubertal and adult (intact and ovariectomized) female rhesus macaques. No GnRH
      neurons were found to contain nuclei that were immunoreactive for the estrogen
      receptor. These results confirm in primates what has been reported in other
      species and leave open the question of how the effects of gonadal steroids on
      GnRH neurons are mediated.

PMID- 7583247
TI  - Eicosanoids are produced by microglia, not by astrocytes, in rat glial cell
      cultures.
AB  - To determine principal sources of eicosanoid production in glial cells, we
      analyzed the metabolites of arachidonic acid in cultured rat glial cells by use
      of reversed-phase, high-performance liquid chromatography and an on-line
      radioisotope detector. Prostaglandin D2, leukotriene B4, leukotriene C4, and 5
      hydroxyeicosatetraenoic acid were present in cultures in which microglia appeared
      on a monolayer astrocytes. None were detected in culture dishes that contained
      only astrocytes, although astrocytes have been believed to be a main source of
      eicosanoid production in brain.

PMID- 7583248
TI  - Selective actions of central mu and kappa opioid antagonists upon sucrose intake
      in sham-fed rats.
AB  - Intake of a palatable sucrose solution in real-fed rats is mediated in part by
      central mu and kappa opioid receptors. Since general opioid antagonists still
      inhibit sucrose intake in sham-fed rats, the present study examined whether
      centrally administered mu (beta-funaltrexamine: 5, 20 micrograms), mu1
      (naloxonazine: 50 micrograms), kappa (nor-binaltorphamine: 1, 5, 20 micrograms),
      delta (naltrindole: 20 micrograms) or delta 1 (DALCE: 40 micrograms) opioid
      subtype antagonists altered sucrose intake in sham-fed rats in a similar manner
      to systemic naltrexone (0.01-1 mg/kg) and whether such effects were equivalent to
      altering the sucrose concentration. Sucrose (20%) intake in sham-fed rats was
      significantly and dose-dependently reduced by naltrexone (59%), beta
      funaltrexamine (44%) and nor-binaltorphamine (62%), but not by naloxonazine,
      naltrindole or DALCE. The reductions in sham sucrose (20%) intake by general, mu
      and kappa antagonism were similar in pattern and magnitude to diluting sucrose
      concentration from 20% to 10% in untreated sham-fed rats. Since both real-fed and
      sham-fed rats share similar patterns of specificity of opioid effects, magnitudes
      and potencies of inhibition, it suggests that central mu and kappa antagonism
      acts on orosensory mechanisms supporting sucrose intake.

PMID- 7583249
TI  - Ethanol enhances muscarinic cholinergic neurotransmission in rat hippocampus in
      vitro.
AB  - Previous studies from our laboratory showed that ethanol enhances muscarinic
      excitatory responses in rat hippocampal neurons in vivo and, like muscarinic
      agonists, reduces the M-current (IM) in these neurons in vitro. Therefore, we
      used extracellular and intracellular recording techniques in the hippocampal
      slice preparation to examine the mechanisms underlying this ethanol-muscarinic
      interaction. Surprisingly, superfusion or local application of low concentrations
      of acetylcholine (ACh), carbachol (CCh) or muscarine reduced the amplitudes of
      CA1 field potentials evoked by stratum radiatum (SR) stimulation. This effect was
      blocked by 1 microM atropine but was independent of the method of agonist
      application, the site of application or the SR stimulus paradigm. In
      intracellular and extracellular single unit recordings, cholinergic depressions
      of field potentials were correlated with: (1) depolarization of pyramidal
      neurons; (2) spike discharge increases; (3) reduction of amplitudes of
      postsynaptic potentials and (4) reduction of late afterhyperpolarizations (AHPs).
      Superfusion of low ethanol concentrations (11-22 mM) alone had little effect on
      SR-evoked field potentials but enhanced (by 10-90%) both the depressions of
      evoked field potentials and depolarizations elicited by the muscarinic agonists.
      Ethanol (22-44 mM) also enhanced both the amplitude and duration of the
      muscarinic slow excitatory postsynaptic potentials (sEPSPs) recorded
      intracellularly in CA1 and CA3 neurons. This effect was enhanced by eserine and
      blocked by atropine, verifying involvement of muscarinic receptors. These results
      suggest that: (1) caution be used in interpreting results of field potential
      studies regarding drug-induced excitability changes; and (2) ethanol in just
      intoxicating concentrations enhances endogenous muscarinic synaptic transmission
      as well as responses to exogenous muscarinic agonists.

PMID- 7583250
TI  - Deposition of apolipoproteins E and J in senile plaques is topographically
      determined in both Alzheimer's disease and Down's syndrome brain.
AB  - The link between the immunolocalization of apolipoproteins E (apo E) and J (apo
      J) and the different severity of beta-amyloid deposition in various areas of
      Alzheimer's disease (AD) and Down's syndrome (DS) brain was analyzed. Both
      apolipoproteins were found in all types of senile plaques (SPs) in the cerebral
      cortex, which is early and severely involved in beta-amyloidosis, but apo E was
      seen more often than apo J in diffuse A beta deposits, especially in young DS
      cases and nondemented elderly persons. In the striatum and cerebellum, which show
      predominance of diffuse A beta deposits throughout the lifespan, apo J was
      absent, except for few compact deposits, whereas apo E was more widely
      distributed, apart from diffuse plaques in the striatum. By immunoelectron
      microscopy, A beta fibrils were disclosed in diffuse plaques in all brain regions
      studied, but not all of these early fibrillar deposits, even in the neocortex of
      young DS cases, showed apo E and apo J labeling. Thus, our data indicate that the
      immunoreactivity to apo E and J within A beta deposits is topographically
      determined in both AD and DS brain. Moreover, although it appears that neither of
      apolipoproteins studied is necessary to initiate A beta fibrillogenesis,
      disclosed topographic dissimilarities of their distribution within parenchymal A
      beta deposits suggest that they may be involved in different ways in the
      pathogenesis of beta-amyloidosis.

PMID- 7583251
TI  - Medial forebrain bundle stimulation in rats activates glycogen phosphorylase in
      layers 4, 5b and 6 of ipsilateral granular neocortex.
AB  - Functional activation in human brain produces an increase in glycolytic
      metabolism. Animal studies suggest activation-induced glycolysis is coupled to
      brain glycogenolysis. Medial forebrain bundle (MFB) stimulation activates the
      release of neurotransmitters which promote neocortical glycogenolysis in vitro.
      In the present study, active glycogen phosphorylase (GP), an index of
      glycogenolysis, is assessed histochemically in rat brain after 15 min of MFB self
      stimulation. Active GP increased significantly in layers 4, 5b and 6 of granular
      neocortex ipsilateral to MFB self-stimulation. Restriction of increased
      glycogenolysis to granular neocortex suggests an important functional interaction
      between sensory neocortical processing and ascending MFB systems.

PMID- 7583252
TI  - Synaptic contact of neuropeptide-and amine-containing axons on parasympathetic
      preganglionic neurons in the superior salivatory nucleus of the rat.
AB  - Parasympathetic preganglionic neurons in the superior salivatory nucleus (SSNNs)
      projecting to the pterygopalatine ganglion were labeled by retrograde transport
      of cholera toxin B subunit (CTB) in the rat. Morphological interactions between
      SSNNs and afferent fibers immunoreactive (IR) for neuropeptide and amine were
      examined with light and electron microscopes by double-immunostaining techniques.
      SSNNs were found in the ipsilateral ventrolateral part of the rostral medulla
      oblongata. Around SSNNs, substance P-, enkephalin-, neuropeptide Y-and
      somatostatin-IR nerve fibers were very rich and tyrosine hydroxylase (TH)-,
      serotonin (5-HT)-, vasoactive intestinal polypeptide- and calcitonin gene-related
      peptide (CGRP)-IR axons showed moderate density. Thyrotropin-releasing hormone
      containing axons were scarce in this region. The electron microscopic
      examinations revealed that CTB-IR structures directly received synaptic input
      from axon varicosities IR for TH, 5-HT and all neuropeptides except for CGRP.
      These findings suggest that catecholamine, 5-HT and the neuropeptides directly
      influence the activity of SSNNs and are concerned with the autonomic regulation
      of nasal and palatal mucosa, lacrimal glands and cerebral blood vessels of the
      rat.

PMID- 7583253
TI  - Effects of scopolamine infusions into the anterior and posterior cingulate on
      passive avoidance and water maze navigation.
AB  - We examined the role of anterior and posterior cingulate cortical muscarinic
      receptors in water maze spatial learning and passive avoidance. Pretraining and
      posttraining trial scopolamine (a mixed a muscarinic acetylcholine antagonist)
      infusions into the anterior cingulate cortex dose dependently (3 no effect; 10
      and 30 micrograms impaired) impaired passive avoidance performance. Pretesting
      infusion into the anterior cingulate had no effect on passive avoidance.
      Scopolamine infusion into the anterior cingulate did not impair spatial
      navigation. On the contrary, scopolamine (3 micrograms no effect, 10 and 30
      micrograms impaired) infusions into the posterior cingulate before daily training
      trials impaired water maze navigation to a hidden platform, but did not affect
      navigation to a visible escape platform or passive avoidance. Posttraining and
      pretesting infusion into the posterior cingulate did not impair WM spatial
      navigation. The present results indicate that muscarinic acetylcholine receptor
      antagonist may modulate passive avoidance performance via cholinergic receptors
      located in anterior cingulate cortex and the ability to develop a spatial
      navigation strategy via muscarinic receptors located in posterior cingulate.

PMID- 7583255
TI  - Interaction between afferent input from fingers in human somatosensory cortex.
AB  - We recorded somatosensory evoked magnetic fields from eight healthy subjects with
      a 122-channel whole-scalp SQUID magnetometer. The stimulus sequence consisted of
      'standard' stimuli (85%) delivered to palmar side of the left thumb with an
      interstimulus interval of 0.6 s and of 'deviants' (15%), randomly interspersed
      among the standards, to little finger, and vice versa. Both stimuli activated
      four source areas: the contralateral primary somatosensory cortex (SI), the
      contra-and ipsilateral secondary somatosensory cortices (SII), and the
      contralateral posterior parietal cortex (PPC). The short-latency (20-40 ms)
      responses originated in the SI cortex, whereas long-latency responses arose from
      all 4 areas. At SII and PPC, the deviant stimuli elicited larger responses when
      presented alone, without intervening standards, than among standards. This
      implies interaction between afferent impulses from the two fingers and/or partly
      intermingled cortical representations. Our findings show, in agreement with
      animal data, different excitatory/inhibitory balance in the various somatosensory
      areas.

PMID- 7583254
TI  - CNTF regulation of astrogliosis and the activation of microglia in the developing
      rat central nervous system.
AB  - In response to physical or chemical brain injury, the mammalian central nervous
      system (CNS) often reacts by evoking astrogliosis. The most prominent feature
      describing this state is an upregulation of glial fibrillary acidic protein
      (GFAP). The agent(s) responsible for inducing astrogliosis remains unclear;
      however, recent observations have shown cytokines may play a pivotal role. During
      CNS trauma, macrophages and lymphocytes infiltrate the CNS where they are thought
      to synthesize and secrete cytokines; moreover, activated microglia and reactive
      astrocytes are known to be capable of cytokine production. We are the first to
      report that an intracerebral injection of the pleiotropic cytokine, ciliary
      neurotrophic factor (CNTF), increases astrogliosis and the appearance of
      activated microglia in the neonatal rat. This response to CNTF was comparable to
      the response observed in animals receiving a well known pro-inflammatory
      cytokine, tumor necrosis factor-alpha (TNF-alpha). Only a moderate increase was
      observed in the proliferative index of cytokine-injected animals; therefore, we
      conclude that GFAP is largely upregulated in a pre-existing GFAP negative cell
      population. Interestingly, coinjections of CNTF and TNF-alpha appeared to act
      synergistically. Coinjected animals displayed a wave of hypertrophied astrocytes
      reaching far into the contralateral hemisphere. No contralateral spreading of
      microglia was observed. This article clearly provides interesting information
      regarding the regulatory mechanisms that govern astrogliosis and discusses the
      probable relationship of reactive astrocytes to microglia.

PMID- 7583256
TI  - Neuronal differentiation of PC12 and chick embryo ganglion cells induced by a
      sciatic nerve conditioned medium: characterization of the neurotrophic activity.
AB  - The present work deals with the finding and characterization of a neurotrophic
      factor present in serum-free Dulbecco's modified Eagle's medium in which rat
      sciatic nerves previously cultured for 9 days were maintained for 24 h. This
      sciatic nerve conditioned medium (SNCM) produced neuronal differentiation and
      neurite outgrowth on PC12 cells, as well as survival and differentiation of eight
      day old chick embryo dorsal root ganglion (E8-DRG) and ciliary ganglion (E8-CG)
      neurons. SNCM activity was decreased by dilution, heating and trypsin treatment;
      it was not inhibited by anti-NGF and anti-bFGF antibodies; and it was not
      mimicked by CNTF, laminin and fibronectin. By utilizing its neurite-promoting
      activity on PC12 cells, experiments oriented to purify the factor were carried
      out. Ultrafiltration, heparin-affinity chromatography and size-exclusion high
      pressure liquid chromatography (HPLC) were employed. The ability of SNCM to
      induce PC12 cell, E8-DRG and E8-CG neuronal differentiation, the heparin affinity
      of the active SNCM protein, and the size-exclusion HPLC elution characteristics
      of the active protein suggest that the active component of the SNCM is, in all
      probability, a novel sciatic nerve neurotrophic factor (SNTF).

PMID- 7583257
TI  - Assessment of cerebral pO2 by EPR oximetry in rodents: effects of anesthesia,
      ischemia, and breathing gas.
AB  - This report describes experiments designed to assess and illustrate the
      effectiveness of a new method for the measurement of cerebral interstitial pO2 in
      conscious rodents. It is based on the use of low frequency electron paramagnetic
      resonance (EPR) spectroscopy with lithium phthalocyanine as the oxygen sensitive
      probe. Magnetic resonance imaging was used to document placement of the probe in
      the brain, and to assess potential cerebral changes associated with the
      placement. The technique provided accurate and reproducible measurements of
      localized pO2 in the brains of conscious rodents under a variety of physiological
      conditions and for time periods of at least 2 weeks. Using this approach we
      quantitated the depressing effects on cerebral pO2 of three representative
      anesthetics, isoflurane, ketamine/xylazine, and sodium pentobarbital. The effects
      of changing the content of oxygen in the breathing gas was investigated and found
      to change the cerebral pO2. In experiments with gerbils, crystals of lithium
      phthalocyanine were implanted in each side of the brain and using a one
      dimensional magnetic field gradient, simultaneous measurement of pO2 values from
      normal and ischemic (ischemia induced by unilateral ligation of a carotid artery)
      hemispheres of the brain were obtained. These results demonstrate that EPR
      oximetry with lithium phthalocyanine is a versatile and useful method in the
      measurement of cerebral pO2 under various physiological and pathophysiological
      conditions.

PMID- 7583258
TI  - Glucose enhancement of scopolamine-induced increase of hippocampal high-affinity
      choline uptake in mice: relation to plasma glucose levels.
AB  - The administration of glucose has been shown to improve memory for various
      learning tasks in rodents. In humans, glucose also increases declarative memory
      performance in elderly people and in some patients with mild Alzheimer's disease.
      One of the possible physiological bases for the effect of glucose on memory
      processes is a facilitation of cholinergic function through increased synthesis.
      In support of this hypothesis, glucose was shown to attenuate the amnesia induced
      by scopolamine and, in similar conditions, glucose increased extracellular levels
      of acetylcholine following a scopolamine injection. To further examine the
      interaction between glucose and cholinergic function, the present experiment
      measured the effects of combined injections of glucose and scopolamine on
      hippocampal sodium-dependent high-affinity choline uptake, an indirect index of
      cholinergic activity. Results showed that the injection of 3 g/kg glucose
      enhanced the increase in high affinity choline uptake in hippocampal synaptosomes
      produced by scopolamine. A regression analysis revealed the existence of a
      positive correlation between plasma blood glucose level and hippocampal choline
      uptake particularly in the animals receiving a combined injection of scopolamine
      and glucose. These data further support the hypothesis that glucose
      administration can facilitate acetylcholine synthesis under certain conditions
      and that this action could explain how glucose attenuates scopolamine-induced
      amnesia.

PMID- 7583259
TI  - Enhanced release of acetylcholine in the rostral ventrolateral medulla of
      spontaneously hypertensive rats.
AB  - We examined whether the altered rostral ventrolateral medulla (RVLM) cholinergic
      function in spontaneously hypertensive rats (SHR) results from enhanced
      presynaptic cholinergic tone. Male 12- to 16-week-old SHR and age-matched Wistar
      Kyoto rats (WKY) were anesthetized, paralyzed and artificially ventilated.
      Unilateral microinjection of cholinergic agents into the RVLM produced a pressor
      response. The pressor response to physostigmine was greater in SHR than that of
      WKY whereas the response to ACh and carbachol was the same in WKY and SHR.
      Bilateral microinjection of scopolamine produced a decrease in blood pressure.
      The depressor response was greater in SHR than that of WKY. When a microdialysis
      probe was placed in the RVLM, ACh release in the RVLM was greater in SHR than
      that of WKY. Choline acetyltransferase (CAT) activity was increased only in the
      rostro-ventral part of the medulla, which contained the RVLM, but not in other
      parts of the medulla oblongata. Physostigmine (0.5 mg/kg, i.p.)-induced increases
      in ACh content were also enhanced only in the rostro-ventral part of the medulla.
      These results provide direct evidence that ACh release in the RVLM is enhanced in
      SHR. It appears that the enhanced cholinergic activity in the RVLM of SHR results
      from an increase in cholinergic impulse flow in the RVLM of SHR. This abnormality
      may play a role in the maintenance of hypertension in SHR.

PMID- 7583260
TI  - Suprachiasmatic nucleus grafts restore circadian function in aged hamsters.
AB  - The regulation of circadian rhythms changes with age. In humans, changes in the
      timing of sleep and wakefulness are especially common. In Syrian hamsters
      Mesocricetus auratus the free running period of the activity/rest rhythm shortens
      with age. The present study tested the hypothesis that critical age-related
      changes occur within the hypothalamic suprachiasmatic nucleus (SCN), known to
      contain a circadian pacemaker. Fetal SCN were transplanted into the brains of
      younger (20 weeks) and older (81 weeks) hamsters which had had their own SCNs
      ablated. The restoration of rhythmicity and the free running period of the
      rhythmicity were determined from continuous records of wheel-running activity.
      Transplantation restored rhythmicity in hosts of both ages. In older hamsters,
      the mean free running period after transplantation was longer than that measured
      before SCN ablation, but a similar lengthening of period was not observed after
      transplantation to younger hamsters. In addition, the mean period after
      transplantation was the same for both younger and older hosts even when there was
      a difference between the groups before SCN ablation. When the grafts were allowed
      to age, the mean free running period of the restored rhythms became shorter,
      indicating that the grafts can also undergo age-related changes. The results
      indicate that age-related changes specifically in the SCN are responsible for an
      age-related change in free running period.

PMID- 7583261
TI  - Taurine prevents haloperidol-induced changes in striatal neurochemistry and
      behavior.
AB  - Repeated daily administration of haloperidol produces changes in striatal
      neurochemistry (decreased dopamine synthesis, upregulation of D2 receptors) and
      behavior (increasing catalepsy). Coadministration of taurine greatly attenuated
      these neuroleptic-induced changes. Possible mechanisms of taurine's mitigating
      effects are its attenuating influences on glutamatergic transmission and its
      actions as a GABAA agonist. The possibility was discussed of adding taurine to
      chronic antipsychotic regimens to block the side-effects typically accompanying
      such therapy.

PMID- 7583262
TI  - Reduced hippocampal CA1 Ca(2+)-induced long-term potentiation is associated with
      age-dependent impairment of spatial learning.
AB  - Expression of Ca(2+)-induced CA1 long-term potentiation (LTP) was analysed in
      hippocampal slices obtained from (1) 3-month-old and (2) 18-20-month-old Sprague
      Dawley rats selected for their performances in the Morris water maze task. In all
      slices, a transient (10 min) increase of extracellular Ca2+ concentration (4 mM)
      caused a long-lasting enhancement of potentials evoked by electrical stimulation
      of radiatum fibers. However, a significant difference was found in the degree of
      potentiation among groups. In particular, increases of the CA1 response
      amplitudes were significantly lower in old rats impaired in spatial learning than
      in young at 30 (P < 0.05), 60, 90 and 120 min (P < 0.01) after restoring the
      normal Ca2+ concentration. On the contrary, no differences were observed between
      young animals and the old ones with good performances in spatial learning. The
      data suggest that amplitude of CA1 Ca(2+)-induced LTP in old rats is related to
      spatial learning abilities.

PMID- 7583263
TI  - Relationship of the ipsilateral rotation in night period and striatal dopamine
      content reduction in unilateral nigrostriatal 6-OHDA lesioned rats.
AB  - In order to discriminate well-lesioned rats after unilateral microinjection of 6
      OHDA into the nigrostriatal dopamine system, we measured the spontaneous rotation
      in the night period and calculated the rate of ipsilateral rotation movement. The
      rate of ipsilateral rotation movement increased along with the total rotation
      movement. The rats with over 95% of ipsilateral rotation kept the rate relatively
      constant for 4 weeks after 6-OHDA lesion and showed a significant increase of
      contralateral rotation (253.2 +/- 37.9) as compared with the rat that had lower
      than 95% ipsilateral rotation (3.6 +/- 1.4) after the injection of apomorphine
      (0.25 mg/kg, s.c.). The reduction percentages of striatal DA contents in animals
      with unilateral rotation over 95% and under 95% to the lesioned side were 97.8 +/
      0.6% and 59.6 +/- 5.8% (P < 0.001), respectively. The rats with over 90%
      reduction of striatal DA levels corresponded nicely to rats with 95% ipsilateral
      rotation among rats injected with apomorphine. These results suggested that the
      evaluation of ipsilateral rotation, taken the level of 95% rotation to the
      lesioned side as a standard, was able to discriminate well-lesioned rats without
      apomorphine treatment after unilateral nigrostriatal 6-OHDA application.

PMID- 7583264
TI  - Decrease in cerebellin and corticotropin-releasing hormone in the cerebellum of
      olivopontocerebellar atrophy and Shy-Drager syndrome.
AB  - Four neuropeptides; cerebellin, corticotropin-releasing hormone (CRH),
      neuropeptide Y and somatostatin were studied by radioimmunoassay in the
      postmortem human brains obtained from three patients with olivopontocerebellar
      atrophy (OPCA) and one with Shy-Drager syndrome. Significant decreases in
      cerebellin and CRH concentrations were found in the cerebellar hemisphere of
      these diseases compared with controls. These findings suggest important
      pathophysiological roles of cerebellin and CRH in these cerebellar diseases. Such
      significant decreases were not found in neuropeptide Y and somatostatin.

PMID- 7583265
TI  - Possible use-dependent changes in adult primate somatosensory cortex.
AB  - Topographic changes in adult primate somatosensory cortical maps have been
      reported to follow well-regulated manipulations in the animals' experience. We
      report briefly here cortical mapping data from one monkey which arrived at our
      laboratory with a chronic paralytic condition in one hand that resulted in a
      unique pattern of skin surface stimulation. Isolated receptive fields across the
      mediolateral extent of cortical area 3b were highly unusual with respect to
      normal topography, but they were completely consistent with the hypothesis that
      the correlated activation of peripheral afferents acts to shape expressed
      cortical receptive fields.

PMID- 7583266
TI  - In vitro thermosensitivity of the midline thalamus.
AB  - This study compared the thermosensitivity and spontaneous activity of thalamic
      midline neurons with those of neurons in areas widely regarded to be involved in
      thermoregulation (preoptic/anterior hypothalamus and posterior hypothalamus). In
      vitro single unit recordings were made from neurons within the thalamic midline
      nuclei, the preoptic/anterior hypothalamus and posterior hypothalamus prior to
      and during a temperature change 3-7 degrees C above and below 37 degrees C. There
      were no significant differences in the degree of thermosensitivity or the
      proportion of thermosensitive neurons in the three areas. In each area examined,
      the thermosensitive neurons had a spontaneous activity which was significantly
      greater than that of the temperature-insensitive neurons. The results suggest
      that structures of the midline thalamus may play a role similar to that of the
      preoptic/anterior hypothalamus and posterior hypothalamus in the processing of
      temperature related information.

PMID- 7583267
TI  - Pituitary adenylate cyclase activating polypeptide enhances rapid eye movement
      sleep in rats.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP), a member of the
      vasoactive intestinal polypeptide family, was tested for its effects on sleep in
      adult male Sprague-Dawley rats. PACAP was injected via intracerebro-ventricular
      cannula at light or dark onset; sleep and brain temperature (Tbr) were recorded
      for 12 h after injection. Rapid eye movement sleep (REMS) was significantly
      enhanced by 30 pmol, but not 3 or 300 pmol PACAP injected at dark onset. Non-REMS
      was not influenced by 3, 30, or 300 pmol PACAP Sleep and Tbr were not influenced
      by 3 or 30 pmol PACAP injected at light onset.

PMID- 7583269
TI  - Post-injury administration of BIBN 99, a selective muscarinic M2 receptor
      antagonist, improves cognitive performance following traumatic brain injury in
      rats.
AB  - Mild to moderate traumatic brain injury (TBI) is associated with enduring
      impairments of cognitive function in both humans and animals. However, few
      experiments have investigated the role of post-injury pharmacologic strategies
      for attenuating the observed cognitive impairment after TBI. This investigation
      examined the effects of selective blockade of the presynaptic muscarinic M2
      autoreceptor with BIBN 99 on cognitive recovery following rodent TBI. Experiment
      1 investigated the effects of delayed post-injury administration of BIBN 99 on
      cognitive performance following moderate central fluid percussion TBI (2.1 +/-
      0.05 atm). On days 11-15 after injury-cognitive performance was assessed with a
      Morris water maze (MWM) task. One hour before MWM testing injured rats were
      injected (s.c.) with either vehicle (n = 9), 0.5 (n = 8), or 1.0 (n = 8) mg/kg of
      BIBN 99. Results indicated that injured rats receiving the delayed post-injury
      treatment with BIBN 99 performed no better than injured-vehicle treated rats. In
      experiment 2, injured rats were injected (s.c.) once daily with either vehicle (n
      = 9), 0.5 (n = 9), or 1.0 (n = 9) mg/kg of BIBN 99 throughout the duration of the
      experiment beginning 24 h after TBI. Sham-injured animals injected (s.c.) with
      vehicle (n = 9) or 1.0 (n = 8) mg/kg of BIBN 99 were included for comparison. On
      days 11-15 after injury, cognitive performance was assessed with the MWM
      procedure. Results of the second experiment indicated that both doses of BIBN 99
      were effective in attenuating cognitive deficits in the MWM as compared to the
      injured-vehicle treated animals (P < 0.05 for both comparisons).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7583268
TI  - Pharmacology of volume regulation following hypotonicity-induced cell swelling in
      clonal N1E115 neuroblastoma cells.
AB  - When exposed to hypotonic solutions, clonal N1E115 neuroblastoma cells initially
      swell and later undergo a regulatory volume decrease (RVD). We studied the
      effects of a variety of transport inhibitors on the time course of cross
      sectional area of N1E115 cells exposed to a solution of reduced osmolarity (pi =
      186 mosm). Application to the bath of either: (i) blockers of net K efflux
      through K channels (e.g. isotonic KCl or 20 mM TEA); or (ii) blockers of net
      efflux through anion channels (e.g. isotonic methanesulfonate, 10 microM DIDS or
      100 microM IAA-94) all prevent RVD. In contrast, ouabain (a Na+/K+ pump blocker),
      bumetanide (a Na+/K+/Cl- cotransporter blocker) and SITS (a HCO3-/Cl- exchange
      blocker) do not. These data support the involvement of these channels over pumps
      or exchangers in solute exit during RVD. Only variable block of RVD was achieved
      using blockers of stretch activated non-selective cation C+ (SA) channels (i.e.,
      amiloride and gadolinium, Gd3+) or a membrane permeant Ca chelator (BAPTA-AM)
      suggesting that neither the opening of C+ (SA) channels nor a global rise in
      cytosolic Ca2+ is critical for triggering RVD.

PMID- 7583270
TI  - Transition from ischemic neuronal necrosis to infarction in repeated ischemia.
AB  - To study morphological changes in the cortex that follow repeated ischemia, one,
      two, and three 7-min unilateral occlusions of the carotid artery at 6-h
      intervals, and three, four, and five 7-min similar occlusions at 12-h intervals
      were produced in gerbils. Animals with one and two 7-min occlusions at 6-h
      intervals showed selective neuronal necrosis in the cortex; those with three 7
      min occlusions at 6-h intervals showed focal infarction in the third layer of the
      cortex. Animals with three 7-min occlusions at 12-h intervals showed selective
      neuronal necrosis; those with four 7-min occlusions at 12-h intervals showed
      focal infarction in the third layer. In animals with five 7-min occlusions at 12
      h intervals, infarction affecting all layers of the cortex was seen. Results of
      the present study indicate that cortical infarction occurred when a brief
      ischemic insult that does not cause any visible morphological damage in cortical
      neurons was inflicted repeatedly, and that development of infarction in the
      cortex following repeated episodes of ischemia depended on both the number of
      insults and the time intervals between them. This finding suggests that there is
      a threshold of infarction in repeated ischemia. In our model, various stages of
      ischemic brain injury could be achieved more easily than in transient ischemia by
      altering the number of insults or the intervals between them. This model is
      suitable for studying the pathophysiology on transition from ischemic neuronal
      necrosis to infarction.

PMID- 7583272
TI  - Oscillations in the discharge frequency of cat primary muscle spindle afferents
      during the dynamic phase of a ramp-and-hold stretch.
AB  - Under a ramp-and-hold stretch the Ia afferent responds to the beginning of the
      ramp phase with an initial frequency peak, which is followed during the ongoing
      dynamic phase of stretching by further frequency peaks. In this investigation the
      behavior of the initial peak is compared with the behavior of the subsequent
      peaks under four experimental conditions: (i) increasing prestretch of the
      muscle, (ii) increasing stretch rate, (iii) change in the waiting time before a
      ramp stretch, (iv) variations in the degree of prestretch preceding a ramp
      stretch, which is then started from a medium degree of prestretch. Under three of
      these four experimental conditions the initial peak behaves qualitatively
      differently from the subsequent peaks. This result gives rise to the
      interpretation that the causes of the initial peak and the subsequent peaks are
      different. The initial peak is caused by a largely synchronous opening of acto
      myosin bonds in the polar parts, whereas the subsequent peaks may be caused by
      intrinsic oscillatory properties of the receptor potential.

PMID- 7583271
TI  - Cell death induced by beta-amyloid 1-40 in MES 23.5 hybrid clone: the role of
      nitric oxide and NMDA-gated channel activation leading to apoptosis.
AB  - The molecular events associated with beta-amyloid-induced neuronal injury remain
      incompletely characterized. Using a substantia nigra/neuroblastoma hybrid cell
      line (MES 23.5) synthetic beta-amyloid 1-40 induced a time and dose-dependent
      apoptotic cell death which was characterized by cell shrinkage and fragmentation
      of DNA, and was inhibited by aurintricarboxylic acid (ATA), and cycloheximide
      (CHX). Following beta-amyloid 1-40 treatment, cyclic GMP, an index of NO
      synthesis, was increased in MES 23.5 cells. The NO scavenger hemoglobin, as well
      as the NO synthase inhibitors NG-monomethyl-L-arginine acetate (L-NMMA) and L-N5
      (1-iminoethyl)ornithine hydrochloride (L-NI0) attenuated such increases. These
      same inhibitors and scavengers also significantly prevented cytotoxicity. beta
      Amyloid also induced an early and transient increase in intracellular calcium as
      monitored with laser scanning confocal microscopy and Fluo-3 imaging. These
      induced calcium transients could be significantly blocked by the N-methyl-D
      aspartic acid (NMDA) receptor antagonist MK-801. Pretreatment with MK-801 or
      removal of extracellular Ca2+ also reduced beta-amyloid-induced NO production and
      neurotoxicity. Furthermore, beta-amyloid neurotoxicity was greatly enhanced in
      the absence of Mg2+ or in the presence of glutamate or NMDA. These data suggest
      that beta-amyloid can lead to apoptotic cell death through a NO mediated process
      possibly triggered by Ca2+ entry through activated NMDA-gated channels.

PMID- 7583274
TI  - Dexamethasone and activators of the protein kinase A and C signal transduction
      pathways regulate neuronal calcitonin gene-related peptide expression and
      release.
AB  - Primary cultures of adult rat dorsal root ganglia (DRG) neurons were used to
      determine if activation of either the protein kinase A or C signal transduction
      pathways or treatment with the synthetic glucocorticoid dexamethasone modulate
      neuronal calcitonin gene-related peptide (CGRP) synthesis and release. DRG are
      the sites of neuronal cell bodies known to produce abundant CGRP levels, and to
      send axons peripherally to blood vessels and centrally to the spinal cord. Using
      immunocytochemical techniques, we confirmed that synthesis of immunoreactive CGRP
      (iCGRP) is restricted to a subpopulation of DRG neurons. Subsequently, we
      determined that treatment (24 h) of the neurons with either dibutyryl cAMP (1 mM)
      or phorbol 12-myristate 13-acetate (2 microM) increased CGRP mRNA content 2.2 +/-
      0.4 (n = 6, p < 0.03) and 3.0 +/- 0.6-fold (n = 6, P < 0.02) respectively, while
      secreted iCGRP levels were increased 1.8 +/- 0.2 (n = 14, P < 0.005) and 4.5 +/-
      1.0 (n = 14, P < 0.001)-fold over control levels. Treatment of the neurons with
      dexamethasone alone had no effect on CGRP expression; however, this agent was
      able to significantly attenuate the stimulatory effects of NGF on both CGRP mRNA
      accumulation and release of iCGRP. Time course studies demonstrated that in the
      phorbol ester treated neurons CGRP mRNA levels continued to increase at 48 h,
      while maximal induction with dibutyryl cAMP occurred at approximately 12 h. These
      results indicate that local and/or circulating factors which act through the
      protein kinase A and C signal transduction pathways upregulate both CGRP
      expression and release, while glucocorticoids attenuate the stimulatory effects
      of NGF.

PMID- 7583273
TI  - Involvement of benzodiazepine/GABA-A receptor complex in ethanol-induced state
      dependent learning in rats.
AB  - State-dependent learning (SDL) induced by ethanol (EtOH) was investigated on the
      step-through passive avoidance task in rats. Pretraining injection of EtOH dose
      dependently reduced step-through latency in the test session 24 h after the
      training. Injection of EtOH (1.0 g/kg) before both the training and test
      sessions, however, failed to reduce the latency. These results show that EtOH
      produces SDL. The failure of learning performance in SDL (dissociation in SDL)
      induced by EtOH was blocked by bicuculline, Ro15-4513 and picrotoxin injected
      before the training session. The success of learning performance in SDL (non
      dissociation in SDL) induced by EtOH was also blocked by bicuculline, Ro15-4513
      and picrotoxin injected before the test session. The antagonism of Ro15-4513
      against EtOH was blocked by flumazenil. In the substitution test, pretest
      injection of EtOH produced non-dissociation in SDL in the both of pretraining
      diazepam-and muscimol-treated rats. On the other hand, neither pretest injection
      of diazepam nor muscimol produced non-dissociation in the pretraining EtOH
      treated rats: asymmetrical cross-substitution between EtOH and diazepam and
      between EtOH and muscimol was observed. These results suggest that the EtOH
      induced SDL is partially mediated by the benzodiazepine (BDZ)/GABA-A receptor
      complex.

PMID- 7583275
TI  - Truncation of IGF-I yields two mitogens for retinal Muller glial cells.
AB  - In the CNS only a truncated form of insulin-like growth factor-I (IGF-I) is
      detected. Although truncated IGF-I (t-IGF-I) retains mitogenicity, growth
      promoting activities have not been detected for the tripeptide that is cleaved
      from IGF-I during truncation. Here, we asked whether the tripeptide is itself a
      growth factor. Using cultured Muller glial cells from the adult human retina, we
      found that the cleaved tripeptide, glycine-proline-glutamate, stimulated the
      proliferation of these cells. Pharmacological experiments indicated that this
      proliferative effect involves activation of N-methyl-D-aspartate (NMDA)
      receptors. In addition, t-IGF-I was also mitogenic in our culture system and had
      an EC50 markedly less than that for IGF-I. Thus, truncation of IGF-I may be a
      mechanism to augment the mitogenic effect of this gene product by creating a more
      potent variant and a cleaved tripeptide that is itself a mitogen.

PMID- 7583276
TI  - In vivo stimulated dopamine release in the nucleus accumbens: modulation by the
      prefrontal cortex.
AB  - In vivo voltammetry was used to measure stimulated dopamine (DA) release in the
      nucleus accumbens following 6-hydroxydopamine (6-OHDA) lesions of the medial
      prefrontal cortex (PFC). Lesions of the PFC resulted in a significant
      potentiation of K(+)-stimulated DA release (383% of control). These data are in
      agreement with other studies which suggest DAergic activation of cortical sites
      can alter the activity of DAergic neurons at subcortical sites. Specifically
      these results suggest that DAergic nerve terminals in the nucleus accumbens are
      tonically inhibited by DAergic activity in the PFC and that alleviation of this
      tonic inhibition produces hyperresponsiveness in the nucleus accumbens.

PMID- 7583277
TI  - Role of nitric oxide in disruption of the blood-brain barrier during acute
      hypertension.
AB  - The goal of this study was to determine the role of nitric oxide in disruption of
      the blood-brain barrier during acute hypertension. We examined the
      microcirculation of the cerebrum in vivo. Permeability of the blood-brain barrier
      was quantitated by the formation of venular leaky sites and clearance of
      fluorescent-labeled albumin (FITC-albumin) before and during phenylephrine
      induced acute hypertension. We compared disruption of the blood-brain barrier
      during acute hypertension in untreated rats and in rats treated for 1 h with
      topical application of NG-monomethyl-L-arginine (L-NMMA; 100 microM) or NG-nitro
      L-arginine methyl ester (L-NAME; 100 microM). Under control conditions, no
      venular leaky sites were visible and clearance of FITC-albumin was minimal in
      untreated rats and in rats treated with topical application of nitric oxide
      synthase inhibitors. Phenylephrine (20 micrograms/kg/min for 5 min) infusion
      increased systemic arterial pressure by a similar magnitude in all groups of rats
      and produced disruption of the blood-brain barrier in venules. However, the
      magnitude of disruption of the blood-brain barrier during acute hypertension was
      significantly less in rats treated with L-NMMA (52% reduction in the clearance of
      FITC-albumin) and L-NAME (47% reduction in clearance of FITC-albumin). The
      findings of the present study suggest that synthesis/release of nitric oxide
      contributes to disruption of the blood-brain barrier during acute hypertension.

PMID- 7583278
TI  - TrkB-like immunoreactivity in trigeminal sensory nerve fibers of the rat molar
      tooth pulp: development and response to nerve injury.
AB  - The localization of TrkB, a signal transducing receptor for brain-derived
      neurotrophic factor and neurotrophin-4, was studied in the rat mandibular molar
      pulp during development and following nerve injury. Sections were incubated with
      rabbit polyclonal antiserum against the catalytic part of the TrkB receptor, thus
      only binding to full-length TrkB receptors, and examined by immunofluorescence
      microscopy and EM immunocytochemistry. At embryonic day 17, strongly TrkB
      positive fibers were located in mandibular nerve trunks, in nerve fibers of
      deeper mesenchyme in close spatial relation to sites of future tooth development
      and in subepithelial nerve plexa. At postnatal days 1-12 intensely TrkB-positive
      nerve fibers surrounded and eventually invaded the developing dental papillae and
      pulps. In the normal adult pulp TrkB-immunoreactive axons were seen extending
      through the radicular pulp into the coronal areas. Double labelling demonstrated
      a considerable overlap between TrkB-like immunoreactivity and low affinity
      neurotrophin receptor-like immunoreactivity in the pulp, although some low
      affinity neurotrophin receptor-positive nerve fibers lacked TrkB-like
      immunoreactivity. Immunogold electron microscopy showed TrkB-like
      immunoreactivity in myelinated as well as in unmyelinated axons. One week
      following inferior alveolar nerve injury there was a dramatic decrease in the
      level of TrkB-like immunoreactivity labelling in the pulp, which paralleled an
      increase in the expression of Schwann cell low affinity neurotrophin receptor
      like immunoreactivity. The first signs of regenerating TrkB-positive nerve fibers
      were found at 4 weeks post-operative, and at 9 weeks the distribution of pulpal
      TrkB-like immunoreactivity had returned to normal. These data indicate that brain
      derived neurotrophic factor and/or neurotrophin-4 could be target-derived factors
      involved in sensory trigeminal tooth pulp nerve fiber development,
      differentiation or regeneration.

PMID- 7583279
TI  - Site-selective acute desensitization following local administration of opioid in
      the hippocampus.
AB  - Electrophoretic administration of the mu selective opioid agonist [D-Ala2, NMe
      Phe4, Gly-ol]-Enkephalin (DAMGO) in the dentate gyrus of the hippocampus acutely
      produces a marked increase in the responsiveness of dentate granule cells to
      perforant path stimulation. This can be measured by an increase in the primary
      population spike (PS) amplitude and by disinhibition in the paired-pulse (PP)
      paradigm. Concomitantly, the spontaneous single unit activity of interneurons is
      usually inhibited. We have observed that after prolonged (usually 10-20 min)
      local (electrophoretic) administration of DAMGO, a second, late effect is noted,
      suggesting acute desensitization. There is a loss of the disinhibition seen in
      the PP paradigm while the primary PS shows only some increased variability in
      response to stimulation. Furthermore, in a time course parallel to the loss of
      disinhibition, single cell activity initially inhibited by DAMGO appears to lose
      its responsiveness. Pretreatment with kappa or delta opioid agonists, or with
      GABA agonists and antagonists, does not affect the development of this
      desensitization suggesting selective involvement of the mu receptor. We further
      propose a regional specificity within the hippocampus since we are unable to
      detect evidence of desensitization to opioid in CA1 using the same techniques.

PMID- 7583281
TI  - Sleep permissive components within the dorsal raphe nucleus in the rat.
AB  - Two peptides known for their hypnogenic properties, CLIP (corticotropin-like
      intermediate lobe peptide or ACTH 18-39) or VIP (vasoactive intestinal
      polypeptide), were injected locally into the nucleus raphe dorsalis (nRD) of rats
      pretreated with p-chlorophenylalanine (PCPA). During the dark period, the PCPA
      insomnia was primarily associated with a reduction in paradoxical sleep (PS),
      whereas both slow wave sleep (SWS) and PS were decreased during the light period.
      Immunohistochemistry of serotonin in PCPA-pretreated animals indicated a clear
      disappearance of 5-HT fibers in the basal hypothalamus and the nRD as compared to
      control animals. Local injections of CLIP or VIP in the nRD restored PS and SWS.
      The positive injection sites corresponded to the anatomical distribution of
      either CLIP or VIP fibers, i.e., the entire nRD for VIP and the antero-dorsal
      part of this nucleus for CLIP. The sleep effects obtained in PCPA-pretreated rats
      involve a non-5-HT sleep permissive component within the nRD upon which these
      injected peptides act.

PMID- 7583280
TI  - Distribution of myelin lipid antigens in adult and developing rat spinal cord.
AB  - We examined the distribution of myelin antigens recognized by monoclonal
      antibodies (mAbs) 01 and 04 in the developing ventral white matter of the
      cervical spinal cord of the rat using immunogold-labeled ultrathin cryosections.
      From the beginning of myelination after birth to multilamellar myelin in adult
      animals, we observed colocalization of 04 and 01 label in myelin. In the
      oligodendrocyte soma, immunolabel was found primarily over Golgi cisternae. In
      the oligodendrocyte processes, immunolabeling was also found in the cytoplasm and
      along the plasmalemma. More cytoplasmic 04 and 01 label was found in the external
      loop of myelin than in the internal loop. The amount of 01 and 04 label increased
      over compact myelin in proportion to the number of lamellae, but the label
      density per unit length of membrane remained approximately the same in compact
      myelin as in oligodendrocyte plasmalemma. We did not see a concentration gradient
      for either 04 or 01 label across, or along multilamellar myelin sheaths.

PMID- 7583282
TI  - Calcium-dependent nitric oxide formation in glial cells.
AB  - We have previously demonstrated nitric oxide (NO)-dependent cyclic GMP (cGMP)
      formation in response to noradrenaline (NA) and glutamate (GLU) in astrocyte
      enriched cultures from rat cerebrum. In the present work we show heterogeneity in
      agonist responses in astrocyte cultures from cerebellum, hippocampus and cortex.
      The response to NA was higher in cells from cerebellum, intermediate in cultures
      from hippocampus and low in cortical astrocytes. GLU had no significant effect in
      cortical and cerebellar cultures and presented lower effects than NA in cells
      from hippocampus. The NO donor sodium nitroprusside (SNP) produced much higher
      cGMP levels than agonists and the order of efficacies was cerebellum > cortex >
      hippocampus. Responses to NA and SNP in cerebellar astrocytes were sensitive to
      culture conditions decreasing when cells were seeded at low density or
      subcultured. Microglial cells were the main contaminants of the cerebellar
      astrocyte cultures but did not contribute to the NA or the SNP responses. No
      soluble guanylyl cyclase or calcium-dependent NO synthase (cNOS) activities were
      detected in microglial cultures. The effect of NA in cerebellar astrocytes was
      blocked by L-arginine analogues and by the alpha 1-adrenoceptor antagonist
      prazosin. The calcium ionophore A23187 mimicked the effect of NA and omission of
      calcium from the medium prevented both responses. NA did not elicit cGMP
      formation in granule cell cultures. These results support an astroglial location
      of the alpha 1-adrenoceptors and the cNOS that mediate NA stimulation of cGMP
      formation in cerebellum.

PMID- 7583283
TI  - Stimulation of dopaminergic amacrine cells by stroboscopic illumination or
      fibroblast growth factor (bFGF, FGF-2) injections: possible roles in prevention
      of form-deprivation myopia in the chick.
AB  - Form-deprivation myopia (FDM) in the chick is a popular model for studying the
      postnatal regulation of ocular growth. Using this model, we have shown previously
      that dopamine and FGF-2 can counteract the effects of form-deprivation, thereby
      producing emmetropia. In the present study, we tested the hypothesis that the
      emmetropizing effects of flickering light and intraocular injections of FGF-2 in
      the chick are mediated by the activity of dopaminergic retinal amacrine cells. We
      have assessed the rate of dopamine synthesis in the retina by measuring the
      accumulation of 3,4-dihydroxyphenylalanine (DOPA). We found that form-deprivation
      reduces the rate of dopamine synthesis in the light-adapted retina, and that the
      normal rate of dopamine synthesis in the light can be restored by stroboscopic
      illumination at frequencies around 10 Hz. By labeling cells immunocytochemically
      we have shown that the synthesis of c-fos, a putative transcriptional regulator
      of the tyrosine hydroxylase gene, is induced in dopaminergic amacrine cells by
      stroboscopic illumination at around 10 Hz. These observations are consistent with
      a critical role for dopaminergic amacrine cells in the regulation of ocular
      growth by intermittent illumination. We have found also that intraocular
      injections of FGF-2 cause emmetropization without altering levels of expression
      of c-fos, amounts of tyrosine hydroxylase, or rates of dopamine synthesis with
      respect to vehicle-injected controls. We conclude that FGF acts either in
      parallel to or downstream from the dopaminergic amacrine cells, rather than
      through them. We observed that intravitreal injection per se induces high levels
      of c-fos expression in both form-deprived and non-deprived retinas, and causes
      partial emmetropization in form-deprived eyes, while inhibiting dopamine
      synthesis in non-deprived retinas. It is likely, therefore, that injection
      stimulates the production and/or release of unknown factors whose diverse effects
      on ocular growth and dopamine metabolism are mediated by complex pathways. Taken
      together, our results are consistent with the view that the retinal circuitry
      that controls postnatal ocular growth in the chick involves multiple messengers
      and pathways.

PMID- 7583285
TI  - Chaotic responses of the hippocampal CA3 region to a mossy fiber stimulation in
      vitro.
AB  - Undoubted evidence of chaotic activity of a biological neural network are given.
      Spontaneous epileptiform bursts of a neuron population in the CA3 region of rat
      hippocampal slices were caused in a perfusing medium with 2 mM penicillin and 8
      mM K+ ions, and responses of field potential in the CA3 region to a periodic
      mossy fiber stimulation were investigated. Phase-locked and chaotic responses
      occur depending on stimulus parameters; for example, when the frequency of the
      stimulation increases, 1:1 phase-locking bifurcates to chaos through 1:2 phase
      locking. The chaotic responses show a broad-band spectrum, and their trajectories
      in the three-dimensional phase space (V(t), V(t + tau), V(t + 2 tau)) reconstruct
      a strange attractor. Lyapunov exponents of the strange attractors estimated by
      the Wolf's algorithm are positive. Moreover, one-dimensional strobomaps obtained
      from the chaotic responses show a non-invertible function. Since the slope of
      each strobomap at their fixed point is more negative than -1, the fixed points
      are unstable. These are undoubted evidences for chaotic responses of the CA3
      region in hippocampal slices maintained in vitro. Cross-correlation functions
      between field potential responses which were simultaneously observed at different
      sites show that the responses are spatially coherent throughout the CA3 region
      even when the responses are chaotic.

PMID- 7583284
TI  - Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe
      epilepsy.
AB  - The distribution of the VIP receptor in the human hippocampus was studied by
      receptor autoradiography using [3-iodotyrosyl-125I]Vasoactive Intestinal Peptide
      (VIP) as a ligand, and the relationship of receptor distribution to the
      distribution of the peptide (visualized by immunocytochemistry) was examined in
      hippocampi surgically removed from patients with medically intractable temporal
      lobe epilepsy (TLE) and hippocampi obtained at autopsy from neurologically normal
      subjects. In the autopsy hippocampi and hippocampi from TLE patients with
      extrahippocampal temporal lobe lesions [125I]VIP binding was highest in the
      dentate molecular layer, with lower levels in the fields of Ammon's Horn (CA
      fields) and the subiculum. In hippocampi from patients with no temporal lobe
      lesions but considerable hippocampal neuronal loss there were significant
      elevations in the levels of ligand binding in all CA fields and the subiculum.
      Ligand binding densities in all CA fields of the patient hippocampi were strongly
      negatively correlated with neuronal numbers. Immunocytochemical localization of
      VIP shows no obvious change in the distribution patters of VIP immunoreactivity
      in the patient groups. This is the first demonstration of VIP and its receptor
      distribution in the human hippocampus. It is suggested that the elevated levels
      of receptor binding in the hippocampal seizure focus may indicate a mechanism for
      greater excitability of neurons and/or for their survivability in the face of the
      increased excitation and potential for injury in a seizure focus.

PMID- 7583286
TI  - Metabolic mapping of rat striatum: somatotopic organization of sensorimotor
      activity.
AB  - Diseases that affect the striatum produce movement disorders, for which rats have
      been a useful model. To determine the organization of functional, neural activity
      in the rat striatum related to motor activity, we used electrical stimulation of
      the motor cortex and [14C]deoxyglucose autoradiography. The stimulation produced
      movements of each of three body regions. Both the motor and somatosensory cortex
      were activated. Image analysis was used to objectively localize peak activation
      and to provide a map for further stereotaxic and localization studies. In the
      anterior striatum, in the dorsolateral sector, regions of peak activation were
      well separated for each body region: the hindlimb peak activation was
      dorsomedial, the forelimb ventrolateral and vibrissae medial. Also, the
      activation fields were larger in anterior than in posterior striatum.
      Furthermore, activation ipsilateral to movement was present and the peak
      localization was offset from peaks contralateral to movement. In addition, there
      were activation regions in lateral striatum where body region representations may
      overlap. This is the first demonstration of a global striatal somatotopy that
      separates the limbs and vibrissae in rats. The functional average revealed by the
      deoxyglucose autoradiography showed a predominant isotropic or rod-like
      representation of sensorimotor activity for the limbs in striatum during movement
      and confirms aspects of the anatomy known for the corticostriate system in
      primates: metabolism was 'patchy,' and extended throughout long anteroposterior
      domains in striatum. These extensive and patchy arrangements suggest integrative,
      combinational and/or associative networks.

PMID- 7583287
TI  - Distribution of glial fibrillary acidic protein (GFAP) in the cochlear nucleus of
      adult and aged rats.
AB  - The age-related change in glial fibrillary acidic protein (GFAP) immunoreactivity
      was analyzed in young (3 months) and old (24 months) adult rat cochlear nuclei
      (CN). Quantitative analyses show a significant increase with age, in the number
      of GFAP positive astrocytes and processes in the old adult when compared with the
      young adult rat. There was also a differential distribution of GFAP
      immunoreactivity in the young adult CN where it predominates in the granular cell
      region, whereas in old rats, the GFAP immunoreactivity distribution was
      homogeneous in all parts of the nucleus. There was no change in the total number
      of neurons between these two stages in any part of the nucleus except for the
      antero-ventral CN, where a decrease in neuronal number was observed in the aged
      rats. The increase in GFAP immunoreactivity was related to an increase of both
      GFAP positive astrocyte number and processes. The increase of GFAP positive
      astrocytes may be due either to an alteration of auditory nerve fibers, changing
      the trophic interactions with post-synaptic cells, or to intrinsic alterations of
      CN neurons and local circuits reflecting aging of the CN.

PMID- 7583288
TI  - 4-Aminopyridine differentially affects the spontaneous release of radiolabelled
      transmitters from rat brain slices in vitro.
AB  - 4-Aminopyridine increased the release of [3H]noradrenaline from dorsal
      hippocampus slices in vitro in a concentration-dependent manner. When the slices
      were exposed to 4-aminopyridine for 5 min, the overflow of radioactivity returned
      to pre-exposure values within 20-25 min. When the exposure of the slices was
      continued, a sustained enhancement of the release of [3H]noradrenaline was
      observed for the duration of the exposure. 4-Aminopyridine, 10(-4) M, had an
      effect of similar magnitude, or an even more pronounced effect, on the release of
      [3H]catecholamine from cortex, septum, periaqueductal gray and striatum slices.
      The effects of the compound on the release of [3H]5-hydroxytryptamine and
      [14C]acetylcholine were less pronounced. At this concentration 4-aminopyridine
      had no effect on the release of [3H]D-aspartate from hippocampus or septum
      slices, whereas the effect on the release of this transmitter in striatal slices
      was marginal. The effect of 4-aminopyridine on the release of [3H]noradrenaline
      in hippocampus slices was largely dependent on the presence of Ca2+ in the
      superfusion medium. This was also the case for the effect on the release of
      [3H]noradrenaline from preloaded dorsal hippocampus synaptosomes. In the presence
      of nitrendipine the effect of 4-aminopyridine was dose-dependently reduced, but
      the maximal reduction, at a nitrendipine concentration of 10(-4) M, was only 40%.
      Cd2+ completely abolished the effect of 4-aminopyridine on the release of
      [3H]noradrenaline. These results confirm that the enhancing effect of 4
      aminopyridine on the release of [3H]noradrenaline depends on the entry of
      extracellular Ca2+ into the nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583289
TI  - Occurrence of the opiate alkaloid-selective mu3 receptor in mammalian microglia,
      astrocytes and Kupffer cells.
AB  - Evidence is presented for occurrence of opiate alkaloid-selective, opioid-peptide
      insensitive receptor binding sites, labeled with [3H]morphine, in primary
      cultures of cat microglia and cat astrocytes, as well as on highly purified
      preparations of rat Kupffer cells. These receptors have been designated mu3 on
      the basis of their close similarity to receptors first found to be present on
      human peripheral blood monocytes. Exposure of the microglia to morphine and
      etorphine caused marked quantifiable changes in cellular morphology, including
      assumption of a more rounded shape and retraction of cytoplasmic processes; in
      contrast, several opioid peptides were without effect on morphology. The effects
      of morphine on microglial morphology were blocked by the opiate antagonist
      naloxone. These effects of drugs on morphology were as predicted for action via
      the mu3 receptor. Opiate alkaloid binding sites previously detected on the rat C6
      glioma cell line were also characterized here as of the mu3 receptor subtype. It
      is proposed that mu3 receptors have broad distribution in different macrophage
      cell types of bone marrow lineage, including microglia and Kupffer cells.
      Furthermore, these receptors are not restricted to cells of bone marrow lineage,
      since they are also present on astrocytes.

PMID- 7583292
TI  - Differences in monosynaptic EPSPs elicited by masseter and temporalis spindle
      afferents in anaesthetised rats.
AB  - We have used the intracellular variant of the spike triggered averaging method to
      examine the monosynaptic connexions of masseter and temporalis spindle afferents
      on jaw-elevator motoneurones. Temporalis spindle afferents elicited larger
      averaged EPSPs in motoneurones than masseter spindle afferents, in part because
      transmission at synapses of temporalis afferents was associated with lower
      incidences of failures. We conclude that EPSP amplitude in this motor system in
      governed, at least in part, by the presynaptic neurone rather than the identity
      of the postsynaptic neurone.

PMID- 7583290
TI  - Determination of microdialysis extraction fraction of cocaine by the no net flux
      method under high, low, and zero steady-state cocaine concentrations in rats.
AB  - The effect of different steady-state cocaine concentration maintenance on the
      microdialysis extraction fraction of cocaine (in situ recovery; Ed) in the medial
      prefrontal cortex (mPFC) was examined. Male, adult Sprague-Dawley rats
      anesthetized with chloral hydrate were used. All rats were randomly divided into
      three groups and were given cocaine i.v. infusion of either 0.6 mg/kg/min (group
      A), 0.3 mg/kg/min (group B), or 0.0 mg/kg/min (group C). A steady-state cocaine
      concentration in the blood was obtained for both A and B groups. They were 24.3
      +/- 2.3 microM, respectively. We then applied the no net flux microdialysis
      method to determine the Ed of cocaine in vivo for all three groups. Results
      revealed that there was no significant difference of Ed under these three
      different infusion regimens (group A: 16 +/- 2%; group B: 17 +/- 1%; group C: 21
      +/- 2%). The steady-state cocaine concentration in the mPFC was also estimated to
      be 17.7 +/- 1.3 microM, 11.3 +/- 2.0 microM, and 0.7 +/- 0.6 microM,
      respectively. We then concluded that the Ed of cocaine in the mPFC is invariable
      while the steady-state cocaine concentration in the mPFC was ranging from 0 to 18
      microM. This information is useful in the cocaine pharmacokinetic study since
      scientists are concerned about the variations of Ed while cocaine concentration
      in the mPFC is changing.

PMID- 7583294
TI  - Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve
      injury and adrenal medullary grafting.
AB  - Excessive activation of N-methyl-D-aspartate (NMDA) receptors in the spinal cord
      consequent to peripheral injury has been implicated in the initiation of
      neuropathologic events leading to a state of chronic hyperexcitability and
      persistence of exaggerated sensory processing. In other CNS disease or injury
      states, NMDA-mediated neurotoxic damage is associated with a loss of NMDA
      receptors, and outcome may be improved by agents reducing NMDA activation.
      Previous findings in our laboratory have demonstrated that the transplantation of
      adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory
      abnormalities and reduce the induction of a putative nitric oxide synthase
      consequent to peripheral nerve injury. In order to determine changes in NMDA
      receptor expression in the spinal cord following peripheral nerve injury and
      adrenal medullary grafting, NMDA receptor binding using a high-affinity
      competitive NMDA receptor antagonist, CGP-39653, and NMDAR1 subunit distribution
      using immunocytochemistry were investigated. Two weeks following peripheral nerve
      injury by loose ligation of the right sciatic nerve, either adrenal medullary or
      striated muscle (control) tissue pieces were implanted in the spinal subarachnoid
      space. Binding studies revealed a marked reduction in [3H]CGP-39653 binding at L4
      L5 levels ipsilateral to peripheral nerve injury in control transplanted animals.
      In contrast, NMDA binding was normalized in adrenal medullary grafted animals. In
      addition, NMDAR1 immunoreactivity was reduced in both the dorsal horn neuropil
      and motor neurons of the ventral horn in animals with peripheral nerve injury,
      while levels in adrenal medullary grafted animals appeared similar to intact
      controls. These results suggest that adrenal medullary transplants reduce
      abnormal sensory processing resulting from peripheral injury by intervening in
      the spinal NMDA-excitotoxicity cascade.

PMID- 7583295
TI  - DNQX inhibits phencyclidine (PCP) and ketamine induction of the hsp70 heat shock
      gene in the rat cingulate and retrosplenial cortex.
AB  - Phencyclidine (PCP) and ketamine are known to block NMDA receptor mediated
      excitotoxicity by non-competitively blocking the NMDA receptor calcium channel.
      PCP and ketamine have the paradoxical effect of also inducing the heat shock
      gene, hsp70, in the cingulate and retrosplenial cortex of the rat. The present
      study shows that DNQX, a specific AMPA receptor antagonist, given as either a 5
      mg/kg or 10 mg/kg intraperitoneal dose or into the lateral cerebral ventricle (5
      microliters of 0.5 mg/ml) significantly diminished PCP (40 mg/kg) and ketamine
      (80, 100, 120 mg/kg) hsp70 induction in the posterior cingulate and retrosplenial
      cortex. The most dramatic decrease of hsp70 induction was seen with the
      intraventricular dose of DNQX. Present findings show that the AMPA receptor has a
      role in PCP/ketamine induction of hsp70 in the cortex. DNQX inhibition of
      PCP/ketamine hsp70 induction was likely related to AMPA receptor antagonism which
      prevented excess calcium influx via voltage-gated calcium channels.

PMID- 7583293
TI  - Effects of systemic and local ethanol on responses of rat cerebellar Purkinje
      neurons to iontophoretically applied gamma-aminobutyric acid.
AB  - The goals of this study were: (1) to determine the effects of acute systemic or
      local application of ethanol (ETOH) on the response of cerebellar Purkinje cells
      (P-cells) to iontophoretically applied gamma-aminobutyric acid (GABA) and (2) to
      characterize the effects of Ro15-4513, a putative antagonist of ETOH-GABA
      interactions, on ETOH-induced changes in GABA responsiveness. Male Sprague-Dawley
      rats (230-370 g) were anesthetized with halothane and implanted with
      intraperitoneal catheters for administration of ETOH (1.0-2.0 g/kg), before the
      recording session. Extracellular activity of single P-cells was recorded with the
      central barrel of a five-barrel micropipette, the other barrels of which were
      used for microiontophoresis of GABA and electro-osmosis of ETOH at the recording
      site. Spontaneous discharge and response of P-cells to GABA were monitored during
      a pre-ETOH control and for 1-1.5 h after systemic or electro-osmotic
      administration of ETOH. Transient suppression of spontaneous P-cell discharge was
      usually observed within 4-8 min of systemic ETOH injection. This effect lasted 2
      4 min in 10 out of 19 rats tested. GABA-mediated inhibitory responses of
      cerebellar P-cells were increased by 45-50% relative to pre-ETOH values at 10 and
      90 min post-ETOH injection. Prior administration of the imidazobenzodiazepine
      Ro15-4513 (4-6 mg/kg) failed to antagonize either the ETOH-induced enhancement of
      GABA-mediated inhibition or the transient inhibition of spontaneous P-cell
      activity rat cerebellar P-cell produced by ETOH. In these studies, electro
      osmotically applied ETOH produced a potent suppression of spontaneous P-cell
      activity which precluded further augmentation of unit responses to GABA. These
      results show that doses of systemically administered ETOH which are mildly
      intoxicating in the awake, behaving animal, enhance the inhibitory action of GABA
      on cerebellar P-cell discharge.

PMID- 7583291
TI  - AMPA receptor antagonism attenuates MK-801-induced hypermetabolism in the
      posterior cingulate cortex.
AB  - The effect of pretreatment with an AMPA receptor antagonist, NBQX, on MK-801
      induced alterations in glucose use was examined using [14C]-2-deoxyglucose
      autoradiography. NBQX (7 mg/kg) had minimal effect on glucose utilisation in all
      anatomical regions examined. The intravenous administration of MK-801 (0.2 mg/kg)
      induced increases in glucose use in the limbic system and cingulate cortex. MK
      801 reduced glucose utilisation in the sensory motor and auditory cortices.
      Pretreatment with NBQX attenuated the MK-801-induced hypermetabolism in the
      posterior cingulate cortex. The decreases in glucose utilisation induced by MK
      801 were not exacerbated by the pretreatment with NBQX. The interaction between
      NBQX and MK-801 suggests a possible method of attenuating some of the adverse
      effects of the non-competitive NMDA receptor antagonists in the posterior
      cingulate cortex.

PMID- 7583296
TI  - Effects of systemic and local ethanol on responses of rat cerebellar Purkinje
      neurons to iontophoretically applied norepinephrine and gamma-aminobutyric acid.
AB  - The goal of the present study was to determine the effect of acute ethanol
      (ETOH), administered intraperitoneally or electro-osmotically, on norepinephrine
      (NE) induced increases in gamma-aminobutyric acid (GABA) mediated inhibition of
      single cerebellar Purkinje neurons (P-cells). Male Sprague-Dawley rats (230-370g)
      were anesthetized with halothane and implanted with an intraperitoneal catheter
      for systemic administration of ETOH (1.0-1.5 g/kg) prior to the recording
      session. Extracellular activity of single P-cells was recorded before and after
      iontophoresis of GABA and NE using five-barrel glass micropipettes. GABA was
      administered at the recording site by microiontophoretic pulses before, during
      and after continuous iontophoretic application of NE. Spontaneous discharge, GABA
      responses and NE-GABA interactions in P-cells were monitored for each experiment
      before and 1-1.5 h following systemic administration of ETOH. As in our previous
      reports administration of NE, at low ejection currents (10-60 nA), augmented GABA
      mediated suppression of P-cell spontaneous discharge. Between 10 and 60 min after
      injection of ETOH, this NE induced augmentation of GABA inhibition was further
      potentiated. This potentiation involved increases in both the magnitude and the
      duration of the GABA inhibition observed after NE alone. NE-induced augmentation
      of GABA inhibition persisted for 2-13 min longer after ETOH administration than
      in the pre-ETOH control period. Local electro-osmotic application of ETOH, which
      resulted in strong depression of spontaneous activity and caused small increases
      in GABA-mediated inhibition, did not directly potentiate NE-induced augmentation
      of GABA action. These results indicate that NE-mediated augmentation of GABA
      inhibition of P-cell activity is potentiated following systemic, but not local,
      ETOH administration.

PMID- 7583298
TI  - Effects of adrenalectomy and corticosterone replacement on glucocorticoid
      receptor levels in rat brain tissue: a comparison between western blotting and
      receptor binding assays.
AB  - A sensitive Western blotting technique, using a commercially available antibody,
      was developed herein to study glucocorticoid receptor (GR) autoregulation in
      brain tissue. A prominent immunoreactive band at approximately 94 kDa,
      representing the GR, was observed in soluble fractions prepared from rat
      hippocampus whereas two bands (approximately 97 and 94 kDa) were detected in
      frontal cortex preparations. Four-day adrenalectomy significantly increased
      immunoreactive GR levels in both brain regions. In contrast, adrenalectomized
      animals implanted with corticosterone pellets of varying concentrations displayed
      dose-dependent decreases in immunodetectable GR levels. Radioligand binding
      assays ([3H]dexamethasone +/- RU 28362), performed on these same tissue
      preparations, revealed a similar pattern of GR response to that measured by
      Western blotting. However, changes in GR binding capacity were generally greater
      in magnitude than corresponding changes in immunoreactive GR levels. This
      discrepancy was most pronounced in adrenalectomized animals administered a bolus
      of corticosterone 1 h prior to sacrifice where a 60-70% reduction in receptor
      binding sites occurred, in sharp contrast to the 25-30% decrease in
      immunoreactive GR levels. Taken together, our findings suggest that Western
      blotting can be used to study GR regulation in brain tissue and that changes in
      steroid-binding capacity may not necessarily reflect changes in receptor protein
      levels.

PMID- 7583299
TI  - C-Fos-like immunoreactivity in the cat brainstem evoked by sneeze-inducing air
      puff stimulation of the nasal mucosa.
AB  - Sneeze is one of the most important protective reflex of the respiratory tract.
      It is elicited from trigeminal peripheral fields and results in major changes in
      the discharge patterns of the medullary respiratory-related neurons. The pattern
      of c-Fos-like immunoreactivity evoked by sneezing was explored as a structural
      approach to the networks involved in this particular model of trigemino-
      respiratory interactions. Sneezes were elicited in anaesthetized adult cats by
      driving air puffs to the superior nasal meatus through a catheter. Additional
      cats were used as controls for anaesthesia and for catheter insertion into the
      nostril. In sneezing cats, immunoreactivity was evoked in projection areas of the
      ethmoidal afferents which innervate the superior nasal meatus, e.g. the subnuclei
      caudalis, interpolaris and in the interstitial islands of the trigeminal sensory
      complex. Immunoreactivity was also markedly enhanced in the areas devoted to
      respiratory control in the medulla (solitary complex, nucleus retroambiguus) and
      in the pontine parabrachial area. C-Fos expression was also evoked in the lateral
      aspect of the parvicellular reticular formation in sneezing cats. This area might
      be of major importance in the adaptation of the ventilatory system to expulsive
      functions.

PMID- 7583297
TI  - Melatonin activates an outward current and inhibits Ih in rat suprachiasmatic
      nucleus neurons.
AB  - Whole-cell voltage-clamp recordings were made from suprachiasmatic nucleus (SCN)
      neurons maintained in horizontal brain slices. The majority of neurons exhibited
      spontaneous and evoked excitatory and inhibitory synaptic currents (EPSC and
      IPSC), mediated by glutamate and GABA respectively. Melatonin had no effect on
      either the spontaneous or evoked EPSC or IPSC. Application of melatonin (0.1-30
      microM) during circadian time (CT) 9-12 activated an outward current at -60 mV
      and increased the membrane conductance in a concentration-dependent manner. The
      current was augmented by depolarization, reduced by hyperpolarization and, in
      some cells, reversed its polarity near the potassium equilibrium potential. Some
      neurons also responded to melatonin during other times of the circadian day (CT 3
      9 or CT 12-15). Hyperpolarizing steps, in a portion of cells, activated an inward
      cation current which resembled the Ih described in other neurons. Melatonin (10
      microM) inhibited activation of the Ih. These data indicate that melatonin may
      inhibit SCN neurons by activating a potassium current and inhibiting the Ih.

PMID- 7583301
TI  - Protection from neuronal damage induced by combined oxygen and glucose
      deprivation in organotypic hippocampal cultures by glutamate receptor
      antagonists.
AB  - Organotypic hippocampal cultures were exposed to defined periods (30 and 60 min)
      of combined oxygen and glucose deprivation, mimicking transient ischemic
      conditions. The involvement of different glutamate receptors in individual
      hippocampal subfields (CA1, CA3 and dentate gyrus) was studied using antagonists
      of NMDA (dizocilpine) and AMPA/kainate receptors (CNQX and GYKI 52466). Staining
      with the fluorescent dye propidium iodide (PI) allowed detection of damaged
      cells. For quantitative determination of neuronal damage, fluorescence intensity
      was measured after a 22 h recovery period and was related to maximal fluorescence
      intensity measured after fixation and PI restaining of the cultures at the end of
      the experiment. Dizocilpine (10 microM), CNQX (100 microM) and GYKI 52466 (100
      microM) provided complete protection in CA1, CA3 and dentate gyrus following the
      moderate ischemic insult, when the antagonists were present permanently. This
      indicates that none of the ionotropic glutamate receptor subtypes dominated
      toxicity in the most sensitive subpopulation of neurons. When applied only during
      the recovery period protection with dizocilpine (10 microM) or CNQX (100 microM)
      was drastically reduced by about 60% in the most sensitive area (CA1), but only
      slightly by 15% in CA3. Therefore the onset of irreversible damage seems to occur
      earlier in CA1 than in CA3. Blockade of AMPA/kainate receptors by GYKI 52466 (100
      microM) offered no neuroprotection if the compound was applied only during the
      recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583303
TI  - Pseudorabies virus mutants as transneuronal markers.
AB  - The transneuronal labeling properties of three genetically engineered forms of
      the Bartha strain of pseudorabies virus (PRV) were studied in the ocular
      sympathetic pathway of rats. Bartha PRV mutants in which expression of the viral
      glycoprotein gI (homologous to gE of herpes simplex virus type 1, HSV-1) was
      restored (Bartha gI+) or which express a wildtype form of glycoprotein gIII
      (homologous to gC of HSV-1 and referred here as Bartha gIIIKa) were analyzed. In
      addition, a Bartha PRV mutant (Bartha beta-gal) containing the lacZ gene encoding
      E. coli beta-galactosidase inserted into the gX gene (homologous to gG of HSV-1)
      was also studied. These were compared to the parental strain--Bartha PRV. The
      pattern of transneuronal labeling in the intermediolateral cell column was
      studied 4 days after 5 microliters of different concentrations of viral stocks
      were injected into the anterior chamber of the eye. The optimal infectious dose
      required to produce the maximal number of cases with specific transneuronal
      labeling of sympathetic preganglionic neurons was determined and these were as
      follows: Bartha PRV = 10(7.5) pfu/ml, Bartha beta-galactosidase = 10(6.5) pfu/ml,
      Bartha gIIIKa = 10(5) pfu/ml, Bartha gI+ = 10(4) pfu/ml. An inverse relationship
      between specificity and infectivity rate was observed. Bartha beta-gal produced
      the greatest number of cases with specific labeling (76%); Bartha gI+ produced
      the lowest level (10%) and thus, this virus is not useful for transneuronal
      labeling studies. Bartha gIIIKa labeled more sympathetic preganglionic neurons
      (second-order neurons) than Bartha beta-gal or Bartha PRV. Bartha gIIIKa and
      Bartha beta-gal viruses labeled more interneurons (third-order) than the standard
      Bartha PRV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583302
TI  - Rapid recovery of rat brain intracellular pH after cardiac arrest and
      resuscitation.
AB  - We studied the intracellular pH in rat cerebral cortex of rats subjected to
      reversible total cerebral ischemia by cardiac arrest and resuscitation. Brain
      acidoses was more pronounced during ischemia in hyperglycemic rats (6.21 +/-
      0.14) than in normoglycemic rats (6.56 +/- 0.07). Brain tissue lactate
      accumulated proportionally. Nevertheless, within 5 min of reperfusion, pHi in
      both normoglycemic and hyperglycemic groups had recovered to baseline levels,
      i.e. near 7.1-7.2, despite the fact that lactate concentrations were still
      elevated. These results demonstrate a rapid reversal of ischemic acidosis during
      recovery from 10 min of cardiac arrest, and suggest that acidosis, per se, may
      not be responsible for neuronal damage following cardiac arrest and
      resuscitation, even in hyperglycemic conditions.

PMID- 7583300
TI  - Subcellular distribution of receptor sites in human brain: differentiation
      between heavy and light structures of high and low density.
AB  - Studies of the subcellular localization of neuroreceptors in the rat brain have
      shown that most of them are associated with light and low density subcellular
      fractions. In two human brain areas, quite different subcellular distributions
      were observed. After fractionation by differential centrifugation of frontal
      cortex homogenates, benzodiazepine and serotonin 5-HT2 receptors were mainly
      found in the heavy mitochondrial (M) fraction, whereas mu-opiate and muscarinic
      cholinergic receptors were mainly concentrated in the microsomal (P) fraction. In
      human putamen, the presynaptic markers of dopaminergic nerve terminals
      (neurotensin receptors, dopamine uptake sites and amine vesicular transporter
      binding sites), benzodiazepine receptors and serotonin uptake sites were
      recovered both in the high and low density fractions, whereas the muscarinic,
      opiate and, to a lesser extent, dopamine D2 receptors were mostly concentrated in
      the microsomal fraction. In the cerebral cortex, after isopycnic centrifugation
      in sucrose gradients, neuroreceptors were found in the high density fractions
      where the peaks of cytochrome oxidase and that of nerve endings, as identified by
      amine uptake and by means of electron microscopy were also found. A single peak
      of benzodiazepine receptors was observed in high density (1.15-1.17 g/ml)
      fractions suggesting that these receptors are much more concentrated in the nerve
      terminals or dendrites rather than in the dendritic spines or vesicles. The fact
      that muscarinic and opiate receptors were recovered in the P fraction with plasma
      membrane constituents and also in M and L fractions, which is confirmed by a
      bimodal distribution in sucrose gradient, suggests that they are localized in
      both the nerve terminals or dendrites and in the small vesicles or dendritic
      spines. In the putamen, much of the specific binding to uptake sites for dopamine
      and serotonin was recovered in the high density fractions, but the existence of
      another peak at a lower density indicates the presence of microsomal uptake
      sites. The results indicate that differential and isopycnic fractionation methods
      performed on human brain samples, make it possible to separate tissue fractions
      enriched in nerve endings, dendrites, dendritic spines, plasma membranes or
      vesicles.

PMID- 7583305
TI  - Phenytoin inhibits expression of microtubule-associated protein 2 and influences
      cell-viability and neurite growth of cultured cerebellar granule cells.
AB  - The objective of this study was to show whether an in vitro model for Phenytoin
      related cytoskeletal impairment could be helpful to investigate cerebellar side
      effects of Phenytoin (DPH). DPH dose-and time-dependently resulted in decreasing
      numbers of vital cells. Cells formed only a rarefied intercellular neuritic
      network. This effect was already evident 24 h after plating. Western-blot
      analysis revealed that the expression of the dendritic marker microtubule
      associated protein 2 (MAP2) was dramatically decreased in DPH-treated cultures.

PMID- 7583304
TI  - Studies on the distribution of vasopressin-immunoreactive neuronal perikarya and
      their fibers in the hypothalamus of Tupaia belangeri.
AB  - The distribution of vasopressin (VP)-immunoreactive neuronal perikarya and its
      fibers had been studied in the hypothalamus of Tupaia belangeri using the avidin
      biotin complex (ABC) immunocytochemical technique. VP-immunoreactive neurons were
      found in the hypothalamic paraventricular nucleus (PVN), supraoptic nucleus
      (SON), accessory supraoptic nucleus (ASN), hypothalamic lateral nucleus (HLN),
      perifornical nucleus (PFN) and ansa peduncularis (AP) but not in the
      suprachiasmatic nucleus (SCN). VP neurons of the rostral PVN could be divided
      into three subnuclei and the caudal PVN could also be divided although not so
      distinctly into four subnuclei. The VP-immunoreactive neuronal perikarya of SON
      were divided into three parts, i.e., medioventral, mediodorsal and laterodorsal.
      Three types of VP neuronal perikarya, i.e., large, medium and small cells,
      existed in PVN and SON. Between PVN and SON, there were a large number of VP
      immunopositive nerve fibers. In addition, there were numerous immunopositive
      fibers projecting into the infundibulum and the neurohypophysis. VP
      immunoreactive-positive products localized in the large granular vesicles and on
      the rough-surfaced endoplasmic reticulum could be seen under electron microscope.

PMID- 7583306
TI  - Mg2+-dependent phosphatase as an inhibitory mediator of the nonselective cation
      current induced by aluminum fluoride in guinea-pig chromaffin cells.
AB  - Internal administration of the G protein activator, guanosine-5'-o-(3
      thiotriphosphate) (GTP gamma S) or aluminum fluoride (AIF) complex, produced an
      inward nonselective cation current (INS) at -55 mV. This current was rapidly
      diminished under conditions of high intracellular Mg2+ ([Mg2+] = 979 microM), the
      half decay time (T1/2) being 80 to 100 s. As [Mg2+] in AlF solutions decreased
      from 400 to 12 microM, the maximum amplitude of AlF-induced INS became larger and
      the current was diminished more slowly. The AlF INS in the presence of 12 microM
      Mg2+ reversed polarity at about +9 mV, irrespective of the extent of decline.
      Bath application of muscarine produced a sustained INS in the absence of AlF
      complex, but in its presence, the overall current comprising a spontaneously
      developed INS and muscarine-induced INS was rapidly diminished. Addition of
      vanadate (0.5 mM) to 979 microM Mg2+ -containing AlF solution mimicked the
      effects of low Mg2+ solution. Inversely, addition of alkaline phosphatase (40
      units/ml) to 12 microM Mg2+ AlF solution reproduced the effects of high Mg2+
      solution. It is suggested that AlF complex deactivates INS through facilitating
      an apparent activity of Mg2+ -dependent phosphatase.

PMID- 7583308
TI  - Decrease in cytosolic Aspartyl-aminopeptidase but not in Alanyl-aminopeptidase
      activity in the frontal cortex of the aged rat.
AB  - To test the neurotoxic hypothesis of excitatory amino acids, we evaluated the
      possible contribution to the free acidic amino acid pool of Aspartyl
      aminopeptidase activity in the frontal cortex of adult (3 month old) and aged
      rats (3 groups of animals aged 26, 29 and 33 months). Aspartyl-aminopeptidase
      activity showed a significant decrease in the oldest rats (29 and 33 months old)
      whereas the activity of Alanyl-aminopeptidase, an unspecific enzyme, did not
      change with age. These data invalidate the idea that excess free acidic amino
      acids are released by aminopeptidases in the aged rat but do provide evidence of
      age-related changes in this enzymatic activity. The possible implications of our
      findings for general alterations in protein degradation are discussed.

PMID- 7583307
TI  - Dopaminergic periventriculo-hypophyseal nerves show tryptophan-hydroxylase
      immunoreactivity but lack serotonin synthesis.
AB  - Hypothalamic dopaminergic periventricular and arcuate nuclei are known to project
      to the pituitary gland and contain serotonin in their terminals. In order to
      elucidate the potential of these neurons to synthesize serotonin, we studied
      immunohistochemically the possible tryptophan hydroxylase content of
      periventriculo-hypophyseal neurons, identified by retrograde tracing from the
      pituitary gland. These neurons were found to contain tryptophan hydroxylase
      immunoreactivity (TpOH-IR), which was enhanced after colchicine treatment. All of
      the TpOH-IR neurons contained tyrosine hydroxylase-immunoreactivity as well.
      However, none of them were immunoreactive for serotonin in either intact animals
      or in animals pretreated with serotonin precursor L-tryptophan and MAO inhibitor
      pargyline. Thus, neurons of the dopaminergic periventriculo-hypophyseal pathway
      express tryptophan hydroxylase, but are unable to synthesize serotonin. These
      findings (i) raise the possibility that, in these nerves, serotonin might serve a
      function other than regular synaptic transmission, and (ii) suggest that
      expression of an enzyme synthesizing certain transmitter does not necessarily
      confirm the corresponding transmitter phenotype of that neuron.

PMID- 7583309
TI  - Activation of endogenous protein kinase C enhances currents through alpha 1 and
      alpha 2 glycine receptor channels.
AB  - The effects of Ca2+ /phospholipid dependent (PKC) phosphorylation on the current
      amplitudes of alpha 1 and alpha 2 glycine receptors expressed in Xenopus oocytes
      were examined by whole cell voltage clamp recording. In studies using phorbol
      esters, PKC phosphorylation has been shown to reduce glycine-induced currents.
      Endogenous PKC activation by pretreatment with serum, however, enhanced the
      currents to around 140% in both alpha 1 and alpha 2 glycine receptors. This
      effect was completely blocked by a specific PKC inhibitor, GF109203X. Instead,
      treatment with a potent PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA)
      revealed a decrease in glycine-gated channel currents. Thus, the present results
      demonstrate that glycine receptor phosphorylation mediated by endogenous pathway
      of PKC activation potentiates glycine-induced currents and phorbol esters may
      have a direct action on glycine receptor channels independent of PKC activation.

PMID- 7583310
TI  - Met-enkephalin-like immunoreactivity in microdialysates from nucleus tractus
      solitarii in piglets during normoxia and hypoxia.
AB  - Met-enkephalin-like immunoreactivity in microdialysates from the respiratory
      related nucleus tractus solitarii was determined simultaneously with ventilatory
      responses in seven, spontaneously breathing, developing swine under conditions of
      normoxia, hypoxia and recovery from hypoxia for 30 min each. Assayed levels of
      Met-enkephalin-like immunoreactivity in normoxia were 0.89 +/- 0.23
      pg/microliters. These levels increased to 203.6 +/- 32.2% and 283.1 +/- 55.8% of
      control during hypoxia and recovery, respectively. Hyperventilation during
      hypoxia was not sustained, comprising brief stimulation followed by return to
      near-control level. Taken together, these results provide further evidence that
      opioid release may contribute to the suppression of ventilation in hypoxia during
      development.

PMID- 7583311
TI  - Preservation of fetal ventral mesencephalic cells by cool storage: in-vitro
      viability and TH-positive neuron survival after microtransplantation to the
      striatum.
AB  - Preservation of fetal ventral mesencephalic (VM) dopaminergic tissue prior to
      transplantation has been hampered by the fact that the cells are vulnerable to
      mechanical and osmotic stress after storage. Previous quantitative studies have
      shown that cool storage in a so-called 'hibernation medium' prior to grafting,
      can be used safely for up to 2 days without morphological or functional losses
      [16,32] using standard transplantation techniques. In the present study on rat
      fetal VM tissue we have investigated (i) the accuracy of different vital stains
      (trypan blue exclusion and ethidium bromide stain) to predict in vivo viability
      of VM cell suspensions after grafting; (ii) the influence of different storage
      media (glucose-saline, HBSS, DMEM, CO2-independent medium and hibernation
      medium), temperatures (+4 degrees C or +21 degrees C) and preparations (cell
      suspension or intact pieces) on the viability scores and total number of cells in
      vitro; and (iii) the survival and functional effects of intrastriatally grafted
      VM tissue after preservation by cool storage for up to 12 days using a less
      traumatic microtransplantation technique. The results show that cool storage at
      +4 degrees C of intact VM pieces in hibernation medium gives the best in vitro
      viability scores. Microtransplantation of cell suspensions prepared from cool
      stored VM tissue produced good survival of tyrosine hydroxylase (TH)-positive
      graft neurons for up to 8 days of storage, and functional compensation in the
      amphetamine-rotation test for up to 12 days of storage. The total yield of
      surviving TH-positive neurons was unchanged, compared to fresh grafts, after 5
      and 8 days of storage, and only reduced by 48% in the grafts stored for 12 days
      prior to implantation. These findings highlight the potential usefulness of a
      combination of cool storage and microtransplantation techniques to be able to
      extend the preservation periods of VM tissue. Such procedures may ultimately help
      to increase the safety and flexibility in experimental and clinical studies on
      neural transplantation of dopaminergic neurons.

PMID- 7583312
TI  - Effect of MPTP on dopaminergic neurons in the goldfish brain: a light and
      electron microscope study.
AB  - The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes a
      Parkinsonian syndrome in the goldfish (Carassius auratus), characterized by
      transient bradykinesia, the accumulation of MPP+ in the brain, and a decrease in
      the forebrain and midbrain content of catecholamines (Pollard et al., FASEB J., 6
      (1992) 3108-3116). Using light and electron microscopy, we studied the effect of
      MPTP on the distribution and ultrastructure of tyrosine hydroxylase (TH)
      immunoreactive, dopaminergic neurons, and on the ultrastructure of other selected
      areas of the goldfish brain. Goldfish were treated with MPTP (50 mg/kg) in the
      absence or presence of L-deprenyl (10 mg/kg) or clorgyline (10 mg/kg). In the
      medial part of the central telencephalon, the nucleus telencephali, pars
      medialis, MPTP caused a decrease in the number of TH-immunoreactive neurons and
      distortions in their labelling pattern. Electron microscopic observations showed
      that MPTP caused swelling of cell processes, changes in neuronal nuclear
      profiles, dilation of endoplasmic reticulum, intracellular vacuolization and
      membrane distortions, and degeneration of neuronal fibers in this brain area.
      MPTP also caused a small reduction and some diffuseness in the labelling of
      dopaminergic neurons in several diencephalic periventricular nuclei. Moreover,
      MPTP induced cell swelling and degeneration in the subependymal cell layers along
      the forebrain ventricles. In all areas, L-deprenyl appeared to partially prevent
      the MPTP-induced degenerative changes. We conclude that in the goldfish MPTP
      causes marked histochemical changes in selected dopaminergic brain systems
      coincident with the Parkinson-like locomotor and neurochemical deficits.

PMID- 7583313
TI  - Changes of opioid binding density in the rat spinal cord following unilateral
      dorsal rhizotomy.
AB  - Mu, delta and kappa opioid receptors in the vertebrate spinal cord mediate the
      potent antinociceptive effects of opioid agonists administered onto the spinal
      cord. The present experiments were conducted to determine the effect of
      unilateral dorsal rhizotomy on mu, delta and kappa spinal opioid binding sites.
      Measurements of opioid binding were made at 1, 2, 4 or 8 days after rhizotomy and
      comparisons were made to intact animals. The changes in mu, delta and kappa
      opioid binding sites were determined by receptor autoradiography using the highly
      selective radioligands [3H]sufentanil, [3H]DPDPE and [3H]U69593, respectively.
      Within autoradiograms of each spinal cord, three regions on each side of the
      spinal cord were targeted for densitometric analysis: laminae I-II (medial), V
      (lateral) and X. When effects of unilateral rhizotomy within animals were
      assessed by comparison of the density of binding on the side ipsilateral to the
      rhizotomy to the contralateral side, decreases in the binding of all three
      radioligands were observed in laminae I-II on the side of the spinal cord
      ipsilateral to the rhizotomy at 2-8 days postlesion. A significant reduction in
      binding was also noted for mu and delta sites in lamina V after 8 days and for
      delta binding in lamina X at 2 and 4 days on the side ipsilateral to the
      rhizotomy. However, when densities of binding sites were compared with the
      corresponding regions in control, it was clear that dorsal rhizotomy resulted in
      significant changes in opioid binding on both sides of the spinal cord; changes
      differed for each type of opioid binding site. On the contralateral side of the
      spinal cord, rhizotomy caused a significant decrease of mu opioid sites 1 day
      after the lesion and showed partial recovery by day 8. Delta opioid sites were
      also significantly decreased as early as 1 day postlesion, but did not recover.
      Kappa opioid sites did not change at 1 day after the rhizotomy but increased on
      day 2, decreased on day 4 and fully recovered 8 days after rhizotomy. The present
      results support the hypothesis that a significant proportion of spinal mu, delta
      and kappa opioid binding sites are present on the central terminations of primary
      afferents. Finally the present data are the first to report a contralateral
      effect of the unilateral rhizotomy on spinal opioid binding sites. The
      contralateral changes in binding were specific to the type of opioid site
      examined, time after the surgery and region of the spinal cord examined.

PMID- 7583314
TI  - A cell-specific role for the adrenal gland in regulating CRH mRNA levels in rat
      hypothalamic neurosecretory neurons after cellular dehydration.
AB  - In the rat, the cellular dehydration induced by water deprivation rapidly
      increases CRH mRNA in magnocellular neurosecretory neurons, but gradually reduces
      mRNA levels in hypothalamic paraventricular parvicellular neurosecretory neurons.
      Using in situ hybridization we investigated a possible role for corticosterone as
      a mediator of the effects of water deprivation on the levels of CRH mRNA in the
      paraventricular and supraoptic nuclei. Following adrenalectomy and water
      deprivation, the reduction of CRH mRNA in the medial parvicellular part of the
      paraventricular nucleus was inhibited. However, replacement of low-doses of
      corticosterone to dehydrated adrenalectomized animals was not sufficient to
      reduce parvicellular CRH mRNA levels to those seen in intact dehydrated animals.
      Neither adrenalectomy nor corticosterone replacement had any effect on the
      increased CRH mRNA levels in magnocellular neurosecretory neurons. We conclude
      that an intact adrenal gland is required for the decreased levels of CRH mRNA
      seen during water deprivation in parvicellular paraventricular neurosecretory
      neurons, but not magnocellular neurosecretory neurons. These effects may be
      mediated by the increased corticosterone secretion seen during water deprivation.

PMID- 7583315
TI  - Characterization of in vivo brain muscarinic acetylcholine receptor subtype
      selectivity by competition studies against (R,S)-[125I]IQNB.
AB  - We have studied the in vivo rat brain muscarinic acetylcholine receptor (mAChR)
      m2 subtype selectivities of three quinuclidine derivatives: (R)-3-quinuclidinyl
      benzilate (QNB), E-(+,+)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo
      1-propen-3-yl)-alpha-phenylacetate (E-(+,+)-IQNP), and E-(+,-)-1
      azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha
      phenylacetate (E-(+,-)-IQNP), and two tricyclic ring compounds: 5-[[4-[4
      (diisobutylamino)butyl]-1-phenyl]-10,11-dihydro-5H-dibenz o [b,e][1,4]diazepin-11
      one [sequence: see text] (DIBD) and 11-[[4-[4-(diisobutylamino)butyl-1
      phenyl]acetyl]-5,11-dihydro-6H- pyrido [2,3-b][1,4]benzodiazepin-6-one [sequence:
      see text] (PBID), by correlating the regional inhibition of (R,S)-[125I]IQNB with
      the regional composition of the m1-m4 subtypes. Subtle effects are demonstrated
      after reduction of the between-animal variability by normalization to corpus
      striatum. Substantial in vivo m2-selectivity is exhibited by QNB and DIBD, modest
      in vivo m2-selectivity is exhibited by E-(+,+)-IQNP, and little or no in vivo m2
      selectivity is exhibited by PBID and E-(+,-)-IQNP. Surprisingly, the in vivo m2
      selectivity is not correlated with the in vitro m2-selectivity. For example, QNB,
      which appears to be the most strongly in vivo m2-selective compound, exhibits
      negligible in vitro m2-selectivity. These examples indicate that a strategy which
      includes only preliminary in vitro screening may very well preclude the discovery
      of a novel compound which would prove useful in vivo.

PMID- 7583316
TI  - Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic
      antidepressant.
AB  - Desipramine (DMI), a tricyclic antidepressant drug used in the treatment of
      depression, has been shown to increase steady-state levels of glucocorticoid
      receptor type II (GRII) mRNA in vitro and in vivo. To determine whether this
      effect is secondary to norepinephrine (NE) reuptake inhibition i.e., increases in
      synaptic NE induced by DMI, GRII mRNA levels were assayed in rat hippocampus
      following neurotoxic lesioning of NE neurons with DSP4. Chronic DMI treatment
      significantly increased GRII mRNA levels to the same degree in lesioned and non
      lesioned animals. In contrast to DMI, the non-tricyclic antidepressant fluoxetine
      had no effect on GRII mRNA. These results provide evidence which demonstrates
      that a tricyclic antidepressant can regulate steady-state mRNA levels in vivo by
      a mechanism which is independent of its effects on synaptic monoamine levels.

PMID- 7583317
TI  - Expression of enkephalin and dynorphin precursor mRNAs in brain areas of hypo-and
      hyperthyroid rat: effect of kainic acid injection.
AB  - An abnormal thyroid status induces morphological and neurochemical modifications
      in the adult brain. In this study we have analyzed the expression of enkephalin
      (ENK) and dynorphin (DYN) precursor mRNAs by means of in situ hybridization in
      the brain of hypothyroid and hyperthyroid rats. The influence of thyroid hormones
      on kainic acid (KA)-induced expression of ENK and DYN mRNAs in the granule cells
      of the dentate gyrus was also studied. Our results can be summarized as follows:
      (1) hypothyroidism induces an up-regulation of ENK mRNA in the granule cells of
      the dentate gyrus and layers V/VI of the cingulate cortex and of DYN mRNA in the
      granule cells of the dentate gyrus; (2) the up-regulation of ENK mRNA expression
      in the granule cells induced by KA is not modified by altered thyroid status; (3)
      in contrast, the KA injection fails to up-regulate DYN precursor mRNA expression
      in the granule cells of the rostral dentate gyrus of the hypothyroid rats; (4)
      injection of KA in hyperthyroid rats increases the expression of DYN mRNA in the
      granule dentate gyrus more than in euthyroid rats. The present results suggest
      that thyroid hormones exert an inhibitory control of expression of ENK and DYN
      mRNAs in selected brain areas. This effect could be directly mediated though the
      thyroid hormone nuclear receptor or could be secondary to changes in
      glutamatergic transmission in the dentate gyrus, as suggested by the profound
      alteration of the KA-induced expression of DYN mRNA in the dentate gyrus of hypo
      and hyperthyroid rats.

PMID- 7583318
TI  - Multiple effects of opiates on intracellular calcium level and on calcium uptake
      in three neuronal cell lines.
AB  - The present study examines the modulation by opiates of intracellular calcium
      levels and calcium entry, using fura-2 imaging and 45Ca2+ uptake, in three
      neuronal cell lines. We show that opiates (10(-7)-10(-5) M morphine and 10(-9)
      10(-7) M etorphine) exert both inhibitory and excitatory effects on KCl-induced
      elevation in intracellular calcium level in SK-N-SH, NG108-15 and NMB cell lines.
      In addition, opiates elevate basal (non KCl-stimulated) intracellular calcium
      level in all three cell cultures. 45Ca2+ uptake is augmented by opiates in SK-N
      SH cells and this stimulatory effect is not blocked by pertussis toxin. In NMB
      cells, an additional inhibitory effect of opiates on basal calcium takes place:
      opiates reduce intracellular calcium level as measured by fura-2, and decrease
      calcium influx as detected by 45Ca2+ uptake. The heterogeneity in the opioid
      regulation of calcium could not be attributed to the type of opioid drug, neither
      to its concentration nor to the experimental conditions, since neighboring cells
      within the same culture responded differently.

PMID- 7583319
TI  - Suicide retrograde transport of volkensin in cerebellar afferents: direct
      evidence, neuronal lesions and comparison with ricin.
AB  - Volkensin and ricin, either free or conjugated with colloidal gold, were injected
      into the cerebellar cortex of rats. The inferior olive and pontine nuclei were
      examined to verify the retrograde axonal transport of these two toxins, and the
      consequent neuronal damage. No evidence was obtained of a retrograde axonal
      transport of ricin in these pathways. Injection of gold-conjugated volkensin in
      the cerebellar cortex resulted in retrogradely labelled neurones in the inferior
      olive after 3 h, and in the pontine nuclei after 6 h. Degenerative changes were
      very severe in the retrogradely labelled neurones 48 h after the gold-conjugated
      volkensin injection. In the Nissl-stained material, neuronal degeneration started
      to be evident in the inferior olive 12 h, and in pontine nuclei 6 h, after
      volkensin injection. The neuronal degeneration in both the inferior olive and
      pons increased up to 4 days after the injection. These findings provide direct
      evidence of the retrograde axonal transport of volkensin in the central nervous
      system, and the time course of the consequent degenerative changes in the
      afferents to the cerebellar cortex.

PMID- 7583320
TI  - gamma-Aminobutyric acid and somatostatin immunoreactivity in the visual cortex of
      normal and dark-reared rats.
AB  - Our previous single unit and ultrastructural studies of visual cortex of dark
      reared rats revealed an impairment of intracortical inhibitory mechanisms
      [2,3,5]. Neurochemical changes in inhibitory neurotransmitter and/or
      neuropeptides, such as gamma-aminobutyric acid (GABA) and somatostatin (SS),
      respectively, may contribute to the observed alterations. The present study was
      designed to measure GABA and SS alterations in the visual cortex of the same dark
      reared preparation, as possible neurochemical correlates of the changes seen both
      physiologically and anatomically in previous companion studies. In the present
      investigation the mean densities of GABA- and SS-immunoreactive neurons in area
      17 of dark-reared rats were determined and compared to the density of those of
      rats reared in normal lighting conditions. Dark-rearing resulted in a significant
      decrease in the density of GABA-immunoreactive neurons in all cell layers of area
      17 of the rat visual cortex; not limited to the thalamorecipient layer(s). There
      was also a higher mean density of total cortical cells in dark-reared animals. No
      differences, however, were seen in the density of SS-immunoreactive neurons. The
      alterations of GABA-immunoreactive neurons in all cortical layers agree with the
      altered synaptic ultrastructure and physiological responses seen in all cortical
      layers as reported in our previous companion studies. Taken together, these
      studies further support the notion of a deficit in intracortical inhibitory
      mechanisms in the visual cortex of dark-reared adult rats.

PMID- 7583321
TI  - Relationship between opioids and activation of phospholipase C and protein kinase
      C in brain injury induced pial artery vasoconstriction.
AB  - Previously, it has been observed that newborn pig pial artery constriction after
      fluid percussion brain injury was associated with elevated CSF dynorphin and beta
      endorphin concentration. Additionally, brain injury reversed dynorphin-induced
      pial artery vasodilation to vasoconstriction. The present study was designed to
      characterize the relationship between opioids and activation of phospholipase C
      (PLC) and protein kinase C (PKC) in brain injury-induced pial vasoconstriction.
      Anesthetized newborn 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. Brain injury decreased
      pial arteriolar diameter within 10 min of injury and continued to fall
      progressively for 3 h (130 +/- 5, 108 +/- 4 and 102 +/- 5 microns for 0, 10 and
      180 min postinjury). In contrast, the PLC inhibitor, neomycin (10(-4) M), blunted
      brain injury-induced pial vasoconstriction (133 +/- 4, 129 +/- 4 and 135 +/- 5
      microns for 0, 10 and 180 min postinjury, respectively). Similarly, staurosporine
      (10(-7) M), a PKC inhibitor, also blunted brain injury-induced vasoconstriction.
      beta endorphin (10(-8), 10(-6) M)-induced pial artery vasoconstriction was
      blunted by neomycin (12 +/- 1, 19 +/- 1 vs. 2 +/- 1, 4 +/- 2% constriction before
      and after neomycin, respectively). Staurosporine similarly blunted beta endorphin
      pial constriction (10 +/- 1, 15 +/- 1 vs. 1 +/- 1, 1 +/- 1% constriction before
      and after staurosporine, respectively). The constrictor potential for dynorphin
      was also inhibited by neomycin and staurosporine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7583322
TI  - Spermine increases paired-pulse facilitation in area CA1 of hippocampus in a
      calcium-dependent manner.
AB  - The effect of spermine on neurotransmission was studied in area CA1 of the
      hippocampal slice preparation. Paired-pulse stimulation (20 ms interpulse
      interval) was delivered to stratum radiatum; the evoked field potential responses
      were recorded simultaneously from stratum radiatum and from stratum pyramidale.
      At mM and sub-mM concentrations, spermine decreased the slope of pEPSP in stratum
      radiatum and the area of the conditioning population spike in stratum pyramidale.
      Short-latency paired-pulse inhibition of the population spike was converted to
      facilitation by spermine. These effects of spermine resembled those observed at
      low calcium concentration. In addition, dose-response and input-output curves
      determined at various Ca2+ concentrations demonstrated that the depressant
      effects of spermine were larger at low Ca2+ levels. The results support the
      notion that spermine competitively blocks presynaptic voltage-sensitive Ca2+
      channels, thus causing a decreased release of neurotransmitter. Since spermine is
      present in brain, it is likely that it is a natural modulator of Ca2+ channels.

PMID- 7583324
TI  - An analysis of astrocytic cell lines with different abilities to promote axon
      growth.
AB  - The adult mammalian central nervous system (CNS) lacks the capacity to support
      axonal regeneration. There is increasing evidence to suggest that astrocytes, the
      major glial population in the CNS, may possess both axon-growth promoting and
      axon-growth inhibitory properties and the latter may contribute to the poor
      regenerative capacity of the CNS. In order to examine the molecular differences
      between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of
      astrocyte cell lines exhibiting a range of axon-growth promoting properties was
      generated and analysed. No clear correlation was found between the axon-growth
      promoting properties of these astrocyte cell lines with: (i) the expression of
      known neurite-outgrowth promoting molecules such as laminin, fibronectin and N
      cadherin; (ii) the expression of known inhibitory molecules such tenascin and
      chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen
      activator inhibitor activity; and (iv) growth cone collapsing activity. EM
      studies on aggregates formed from astrocyte cell lines, however, revealed the
      presence of an abundance of extracellular matrix material associated with the
      more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell
      lines was assessed for axon-growth promoting activity, matrix from permissive
      lines was found to be a good substrate, whereas matrix from the inhibitory
      astrocyte lines was a poor substrate for neuritic growth. Our findings, taken
      together, suggest that the functional differences between the permissive and the
      inhibitory astrocyte cell lines reside largely with the ECM.

PMID- 7583323
TI  - Vestibular inputs to the lateral tegmental field of the cat: potential role in
      autonomic control.
AB  - The lateral tegmental field (LTF), which is comprised of the lateral reticular
      formation near the obex, is an important integrative area involved in
      cardiovascular control and the production of emesis. Using neuroanatomical and
      electrophysiological techniques, we tested the hypothesis that LTF neurons
      receive vestibular inputs; the neurons studied included those projecting into the
      subretrofacial rostral ventrolateral medulla (sRVLM), which contains cells that
      make direct connections with sympathetic preganglionic neurons. Injections of the
      anterograde tracer PHA-L into the medial and inferior vestibular nuclei produced
      labeled terminals in the LTF. Electrical stimulation of the vestibular nerve
      affected the firing rate of LTF neurons, including approximately one-third of
      those antidromically activated from the sRVLM. The response latencies ranged from
      1.5 to 20 ms, suggesting that the neurons received both direct and polysynaptic
      vestibular inputs from the vestibular nuclei. The LTF may be involved in the
      production of vestibulosympathetic reflexes and vestibular-elicited vomiting.

PMID- 7583325
TI  - Recovery of vibrissae-dependent behavioral responses following barrelfield damage
      is not dependent upon the remaining somatosensory cortical tissue.
AB  - Previous work has demonstrated that damage to the primary somatosensory cortex
      produces substantial deficits in a vibrissal cue-dependent discrimination task
      which recover gradually over the course of post-injury testing. The present study
      was designed to evaluate the possible site(s) and mechanisms underlying
      behavioral recovery in this task. Wistar rats were trained under red light in a T
      maze to produce ipsilateral turns depending upon the presence of a vibrissal cue.
      Animals were then subjected to photothrombotic infarctions of either the
      ipsilateral medial parietal cortex, the ipsilateral primary and secondary
      somatosensory cortex (SI/SII), the primary and secondary somatosensory cortices
      of both hemispheres (bilateral SI/SII) or sham surgical procedures. Behavioral
      testing resumed 24 hours following surgery, and continued for a total of 60 days.
      The performance of animals with infarcts restricted to the medial parietal cortex
      did not differ from that of sham-operated controls. Animals with either
      unilateral or bilateral SI/SII infarcts exhibited a significant decrease in
      percent correct responding as compared to shams and rats in the medial parietal
      group. These deficits recovered to pre-infarct levels over approximately 35-40
      days. This rate of recovery was slower than the recovery exhibited by animals
      given medial parietal infarcts which spared the primary barrelfield cortex. The
      results of this study suggest that neither the contralateral somatosensory cortex
      nor the vibrissal representation within ipsilateral SII cortex play a critical
      role in the recovery process. The possibility that subcortical structures
      underlie the deficits observed following barrelfield cortical damage is
      discussed.

PMID- 7583326
TI  - Postnatal maturation of the blood-brain barrier for unbound bilirubin in newborn
      piglets.
AB  - The postnatal maturation of the blood-brain barrier (BBB) for unbound bilirubin
      was studied in 2-day- and 2-week-old piglets. Hyperbilirubinemia was induced by
      bolus infusion of bilirubin at 25 mg/kg followed by continuous infusion of 20
      mg/kg/h for 3 h. During the study period, arterial blood pH and blood gas
      tensions, serum osmolarity, and mean arterial blood pressures were within the
      physiologic range. Brain bilirubin content and the brain/blood distribution ratio
      for bilirubin were higher in the 2-day-old than in the 2-week-old piglets. In
      both age groups, regional brain bilirubin concentration and brain/blood ratios
      were higher in subcortical regions (cerebellum and brainstem) than in the
      cerebral cortex. We conclude that in newborn piglets the blood-brain barrier for
      unbound bilirubin matures with increasing postnatal age and that irrespective of
      maturity the relative permeability of the BBB for bilirubin appears higher in
      subcortical than in cortical regions.

PMID- 7583327
TI  - Changes in hypothalamic prostaglandin E2 may predict the occurrence of sleep or
      wakefulness as assessed by parallel EEG and microdialysis in the rat.
AB  - Prostaglandin (PG) E2 is produced by mammalian hypothalamus and when administered
      exogenously prolongs wakefulness. In order to study the relation of endogenous
      hypothalamic PGE2 to sleep and wakefulness, we have used microdialysis in freely
      moving rats associated with EEG recording. Male Wistar rats were implanted with
      three cortical electrodes and with a guide cannula for microdialysis in the space
      between the paraventricular nucleus (PVN) and the ventromedial hypothalamus
      (VMH). PGE2 was measured by RIA in 3- or 6-min dialysates 15 days after surgery,
      when sleep patterns were normal again and PGE2 production stabilised. PGE2 levels
      were significantly higher during wakefulness (601 +/- 35 pg/ml, 5 experiments, 35
      samples) than during slow-wave sleep (487 +/- 24 pg/ml, 5 experiments, 49
      samples). Samples corresponding to paradoxical sleep showed a tendency towards
      higher PGE2 values compared to slow-wave sleep but lower compared to wakefulness.
      In epochs of wakefulness or sleep lasting at least 12 min, high PGE2 levels in
      the middle of wakefulness regularly dropped, thus announcing the occurrence of
      sleep. During sleep, PGE2 first went on dropping and then reincreased towards the
      values that characterize early periods of wakefulness. In its turn, this
      reincrease in PGE2 announced the end of sleep and the imminent occurrence of
      wakefulness. It is the first study to our knowledge showing that the evolvement
      in endogenous PG profile may predict the occurrence of sleep or wakefulness.

PMID- 7583328
TI  - Cholecystokinin-induced release of dopamine in the nucleus accumbens of the
      spontaneously hypertensive rat.
AB  - Changes in dopamine neurotransmission in the nucleus accumbens of the
      spontaneously hypertensive rat (SHR) may be involved in the pathogenesis of
      hypertension. This investigation tested the hypothesis that the sulfated
      octapeptide cholecystokinin (CCK8S) induced release of dopamine is greater in the
      SHR than in its normotensive control, the Wistar-Kyoto rat (WKY). Dopamine and
      its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      were sampled using microdialysis in the caudal half of the nucleus accumbens of
      10-week-old anesthetized SHRs and WKYs. Samples were collected in the following
      order: 3 baseline, 3 CCK8S (10 mumol/l), and 3 postdrug samples. The samples were
      then analyzed using high pressure liquid chromatography with electrochemical
      detection. CCK8S increased dopamine and DOPAC levels in both the SHR and WKY with
      a larger increase in basal dopamine in the SHR (greater than 200%). Perfusion of
      the nucleus accumbens with 1 mumol/l of CCK8S or the nonsulfated form of CCK8
      (CCK8US, 10 mumol/l) produced no significant increase in the release of dopamine
      in the SHR. These results indicate that CCK8S-induced release of dopamine in the
      nucleus accumbens is greater in the SHR. Changes in CCK8S
      neurotransmission/receptor function may be responsible for the alterations in
      dopaminergic function of the SHR and the pathogenesis of hypertension.

PMID- 7583329
TI  - Estrogen-receptive neurons in the anteroventral periventricular nucleus are
      synaptic targets of the suprachiasmatic nucleus and peri-suprachiasmatic region.
AB  - The anteroventral periventricular nucleus (AVPv) in the rat preoptic area is a
      key site underlying control of the steroid dependent preovulatory gonadotropin
      surge. Estrogen and progesterone receptor-containing neurons in the
      preoptic/hypothalamic continuum, particularly those in the AVPv, are believed to
      transduce steroidal signals and, in turn convey this information to the LHRH
      system, which lacks steroid receptors. In addition to the influence of the
      gonadal steroids, the precise timing of the preovulatory gonadotropin surge is
      believed to be regulated by the hypothalamic suprachiasmatic nucleus (SCN). The
      SCN and peri-SCN neurons send efferent projections rostrally to the anterior
      preoptic area suggesting that circadian signals are communicated synaptically to
      steroid-responsive neurons in the AVPv. To test this hypothesis, ultrastructural
      double label immunocytochemistry was conducted to determine whether SCN efferents
      contact estrogen receptor-immunoreactive neurons in the AVPv. Brain sections with
      SCN injections of phaseolus vulgaris leucoagglutinin (PHA-L) were immunostained
      for estrogen receptors and PHA-L. Light and electron microscopic data show that
      the anterior preoptic area received robust PHA-L-immunoreactive efferents from
      SCN neurons and immediately adjacent subparaventricular zone. In particular, the
      AVPv contained abundant labeled fibers and terminal boutons. Ultrastructurally,
      SCN- and subparaventricular zone-derived terminals synaptically contacted the
      perikaryon of many estrogen receptor-immunoreactive neurons in the AVPv. The
      perikarya of unlabeled neurons were also contacted, but the majority of the
      labeled contacts were observed upon neuronal processes. These results demonstrate
      that estrogen responsive AVPv neurons are regulated by SCN efferents.
      Furthermore, the present data provide strong support to the idea of collective
      control of pituitary gonadotropin release by steroid sensitive and circadian
      signal neural pathways.

PMID- 7583331
TI  - Expression of a glycosyl phosphatidylinositol-anchored adhesion molecule, the
      glycoprotein F3, in the adult rat hypothalamo-neurohypophysial system.
AB  - The F3 cell surface glycoprotein consists of six immunoglobulin-like domains,
      four fibronectin type III repeats and a glycosylphosphatidylinositol anchor and
      is found in membrane-bound and soluble form. Until now, it has been localized
      mainly on axons of subsets of developing and postnatal neurons and has been
      implicated in axonal growth and synaptogenesis. We here examined its expression
      in the adult rat hypothalamo-neurohypophysial system composed of magnocellular
      neurons whose axons can undergo remodelling in adulthood in response to lesion or
      physiological stimulation. Immunoblot analyses demonstrated high levels of F3
      immunoreactivity in the hypothalamic nuclei containing the somata of the neurons,
      in the median eminence, through which pass their axons and in the
      neurohypophysis, where they terminate. The amount of F3 detected in the latter
      was 2-fold that in the hypothalamus. In addition, soluble forms predominated in
      the neurohypophysis and GPI-linked forms in the hypothalamus. Immunocytochemistry
      revealed a strong F3 immunoreactivity throughout the neurohypophysis and internal
      layer of the median eminence, characterized by a punctate labeling of fibers and
      dense filling of dilatations. In the hypothalamic nuclei, staining of variable
      intensity was visible in the cytoplasm of some magnocellular somata. In contrast,
      in colchicine-treated rats, all magnocellular somata throughout the hypothalamus
      displayed intense labeling while staining in the neurohypophysis was greatly
      reduced. Our observations reveal that neurons of the adult hypothalamo
      neurohypophysial system express high level of F3, even under normal conditions.
      In view of its distribution and the differing proportions of membrane-bound and
      soluble forms, we propose that, after synthesis in the hypothalamus, F3 is
      targeted to the neurohypophysis where it accumulates in neurosecretory terminals
      or is released into the extracellular space. It remains to be seen whether its
      expression is linked to the secretion of the neurohypophysial peptides and in
      particular, to the ability of these neurons to undergo structural remodelling in
      adulthood.

PMID- 7583334
TI  - Effects of afferent firing frequency on the amplitude of the monosynaptic EPSP
      elicited by trigeminal spindle afferents on trigeminal motoneurones.
AB  - We have examined the effect of changes in afferent firing frequency on the
      monosynaptic EPSP elicited by trigeminal muscle spindle afferents in elevator
      motoneurones, using both paired pulse and repetitive activation of the masseter
      nerve. Both modes of stimulation resulted in significant facilitation of EPSP
      amplitude over intervals of 5-19 ms, but no significant change in EPSP amplitude
      at either longer or shorter intervals. The facilitation obtained stands in
      contrast to the predominant depression of EPSP amplitude reported in hindlimb
      motoneurones following stimulation at decreasing intervals.

PMID- 7583332
TI  - Potentiation of excitatory postsynaptic potentials by a metabotropic glutamate
      receptor agonist (1S,3R-ACPD) in frog spinal motoneurons.
AB  - We conducted intracellular recordings of lumbar motoneurons in the arterially
      perfused frog spinal cord and investigated the effects of a metabotropic
      glutamate receptor agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid
      (ACPD), on excitatory postsynaptic potentials evoked by stimulation of the
      descending lateral column fibers (LC-EPSPs). In the absence of Mg2+, ACPD
      reversibly potentiated the amplitude of monosynaptic LC-EPSPs by more than 15% in
      15 of 19 cells with 5 microM ACPD and in 7 of 12 cells with 0.5 microM ACPD. The
      EPSP amplitudes with 5 and 0.5 microM ACPD were 142 +/- 10% (mean +/- S.E.M., n =
      19) and 130 +/- 13% (n = 12) of the controls. The potentiation was seen without a
      decrease in the input conductance. Glutamate-induced depolarizations in the
      absence and the presence of 0.5 microM ACPD were not significantly different in
      cells perfused with the low Ca(2+)-high Mg2+ solution which eliminated chemical
      transmission. Paired pulse facilitation of LC-EPSPs was reversibly decreased in
      association with the potentiation. ACPD-induced potentiation of monosynaptic LC
      EPSPs was seen in 5 of 6 cells in the presence of D-(-)-2-amino-5
      phosphonopentanoic acid (D-AP5), an NMDA receptor antagonist. ACPD occasionally
      activated polysynaptic components of LC-EPSPs which were mediated mainly via NMDA
      receptors. On the other hand, ACPD-induced potentiation of EPSPs was inhibited by
      extracellular Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583333
TI  - Neural activity of chorda tympani mechanosensitive fibers during licking behavior
      in rats.
AB  - The chorda tympani nerve, supplying the anterior two-thirds of the tongue,
      contains gustatory and mechanosensitive afferent fibers. We have analyzed
      discharge patterns in rats of various fibers recorded from dissected nerve
      filaments during licking behavior of which 4 were taste-sensitive and 12
      mechanosensitive. The incidence of these two types were estimated
      electrophysiologically under anesthesia and their conduction velocity measured.
      Recordings in freely moving animals showed that the mechanosensitive fibers
      innervating the dorsal part of the tongue gave two burst discharges per lick,
      suggesting that contact of the tongue with the upper incisors and/or lip occurred
      during tongue protrusion and retraction. The fibers from the tip of the tongue
      showed one burst discharge per lick, which was the response to contact with a
      drinking spout. No rhythmical discharges synchronized with lick signals were
      observed in the fibers from the lateral part of the tongue or the taste-sensitive
      fibers. Such mechanoreceptor discharges were difficult to detect in recordings
      from the whole chorda tympani nerve. This masking of responses was due mainly to
      activation of a small number of mechanosensitive fibers by licking-induced
      mechanical stimulation. The lubricating action of saliva also decreased
      mechanoreceptor sensitivity. Despite their small number, the mechanosensitive
      fibers had axons with faster conduction velocities (larger diameter) than the
      taste-sensitive fibers. This was probably the reason why dissected nerve bundles
      more frequently showed mechanical than taste responses in conscious rats.

PMID- 7583335
TI  - Investigation of synergism in binary mixtures of sweeteners.
AB  - The purpose of the present study was to determine the presence and degree of
      synergism among all binary mixtures of 14 sweeteners varying in chemical
      structure. A trained panel evaluated binary combinations of the following
      sweeteners: three sugars (fructose, glucose, sucrose), two polyhydric alcohols
      (mannitol, sorbitol), two diterpenoid glycosides (rebaudioside-A, stevioside),
      two dipeptide derivatives (alitame, aspartame), one sulfamate (sodium cyclamate),
      one protein (thaumatin), two N-sulfonyl amides (acesulfame-K, sodium saccharin),
      and one dihydrochalcone (neohesperidin dihydrochalcone). Each sweetener was
      tested at three concentrations that were isosweet with 3%, 5%, and 7% sucrose.
      Two methods of analysis were performed to determine synergistic effects. In
      Method I, an ANOVA was performed for each intensity level to determine if the
      mean sweetness intensity ratings of each binary mixture were equal to nominal
      sweetness (i.e., additivity) or not equal to nominal sweetness (i.e., synergism
      or suppression). In Method II, an additional ANOVA was performed to determine if
      the sweetness intensity ratings of any given mixture were equal to or greater
      than the average of the sweetness ratings of the two pure components in that
      blend.

PMID- 7583330
TI  - Spinal cord neurons are vulnerable to rapidly triggered kainate neurotoxicity in
      vitro.
AB  - Initial studies found glutamate injury to murine spinal cultures (14-17 days in
      vitro) to reflect contributions of both NMDA and AMPA/kainate receptors.
      Subsequent experiments found the spinal cultures to be more sensitive than
      cortical cultures to injury from prolonged low level kainate exposures, and,
      unlike cortical cultures, to be significantly damaged by relatively brief (30-60
      min) kainate exposures. This rapidly triggered kainate damage to spinal neurons
      is Ca(2+)-dependent. Also, more than 40% of spinal neurons (in comparison to
      about 15% of cortical neurons) are subject to kainate-activated Co2+ uptake
      (Co2+(+) neurons), a histochemical technique that labels neurons with Ca(2+)
      permeable AMPA/kainate channels. These spinal Co2+(+) neurons are very sensitive
      to Ca(2+)-dependent kainate injury, and show greater kainate-induced elevations
      in intracellular Ca2+ concentrations ([Ca2+]i) than other spinal neurons during
      low level kainate exposures. Thus, the heightened vulnerability of spinal neurons
      to kainate toxicity may at least in part reflect the large proportion that
      possess Ca2+ permeable AMPA/kainate channels, permitting receptor activation to
      trigger rapid Ca2+ influx and overwhelm the cells Ca2+ homeostatic capabilities.

PMID- 7583336
TI  - Lesion with the neurotoxin AF64A alters hippocampal cholinergic receptor
      function.
AB  - The effect of selective lesion of cholinergic inputs to the hippocampus on the
      function of hippocampal cholinergic receptors was examined. Hippocampal
      cholinergic neurons were lesioned in the rat by administration of the selective
      cholinergic neurotoxin AF64A (ethylcholine mustard aziridinium). Cholinergic
      receptor function was examined by assessing the ability of cholinergic agonists
      and antagonists to modulate the evoked release of radiolabelled acetylcholine
      (ACh) from hippocampal slices. Nicotine enhanced release, with a bell-shaped dose
      response curve. The dose-response curve and EC50 for nicotine was shifted 10-fold
      to the left in lesioned rats, suggesting an increased sensitivity to nicotine.
      However, there were no differences in either the number of affinity of nicotinic
      receptors as determined with binding studies. The muscarinic agonist oxotremorine
      inhibited the evoked release of ACh in control tissues, but had much less effect
      in AF64A-lesioned tissues. Binding to the M1 receptor subtype was not changed.
      However, the Kd for binding to the high affinity subtype of the M2 receptor was
      increased 10-fold, suggesting that the receptor has become less sensitive to
      stimulation. Loss of M2 function may allow an increase in the effect of
      stimulating nicotinic receptors that modulate ACh release.

PMID- 7583339
TI  - Early postnatal diazepam exposure facilitates maternal behavior in virgin female
      rats.
AB  - Virgin female rats do not display maternal behavior if they are not exposed to
      the pups during several days. This exposure is called induction. In this work we
      have studied the effects of early postnatal (PO-P16) diazepam (DZ) administration
      (1 and 2.5 mg/kg, SC) on the display of maternal behavior of virgin female rats
      when adults. Although we did not find statistically significant differences
      between P0-P16 DZ treated and control females with respect to the latency of
      retrieval, P0-P16 DZ administration resulted in a statistically significant
      increase of the percentage of female rats that became maternal, showing retrieval
      behavior. This early postnatal treatment with DZ also increased other variables
      that are currently measured in maternal behavior tests, such as: time of physical
      contacts, grooming, crouching, and nest building quality. No statistically
      significant differences were found in the body weight of treated versus control
      animals during development, nor during adulthood. Our results provide further
      evidence that the GABAA-BDZ-Cl- receptor complex is implicated in the development
      of maternal behavior in female rats.

PMID- 7583338
TI  - CNS levels of mu opioid receptor (MOR-1) mRNA during chronic treatment with
      morphine or naltrexone.
AB  - The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution
      hybridization in rats treated chronically with morphine or naltrexone. Morphine
      treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4)
      resulted in the development of tolerance to morphine's antinociceptive
      (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7.
      Following the hot plate test, selected CNS regions were obtained by
      microdissection. The levels of MOR-1 mRNA in pg/microgram RNA ranged from 0.7 in
      sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not
      altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal
      grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate
      experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on
      CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was
      detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial
      thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in
      alterations in the size of full-length MOR-1 mRNA from rat brain, or in the size
      of the region protected by the MOR-1 riboprobe (i.e., the entire coding region).
      Thus, the neuroadaptive processes associated with the development of analgesic
      tolerance to morphine do not involve concurrent changes in the steady-state
      levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a
      region-specific downregulation of MOR-1 mRNA levels, which may be secondary to
      the naltrexone-induced increase in mu receptor binding.

PMID- 7583337
TI  - Focal 2-DG uptake persists following olfactory bulb lesions.
AB  - Exposure of rats to different odors produces spatially distinct patterns of 14C-2
      deoxyglucose uptake (2-DG) in the glomerular layer of the main olfactory bulb.
      However, lesions of specific regions of the bulb that reliably contain 2-DG foci
      reportedly do not impair the ability of rats to perform olfactory-guided
      behaviors, suggesting that the lesioned olfactory bulb retains odor
      responsiveness. Because the absence of focal 2-DG incorporation in lesioned
      olfactory bulbs has not been verified by 2-DG autoradiography, it cannot be
      concluded that focal responses in the olfactory bulb do not contribute to the
      encoding of olfactory information. To examine the effects of bulb lesions on 2-DG
      uptake in the olfactory bulb, we placed lesions in specific regions of the bulb
      that reliably contain 2-DG foci. We then exposed rats to odors 3 or 6 weeks later
      to determine if the lesions effectively eliminated focal 2-DG uptake in these
      bulbs. The results indicate that lesioned olfactory bulbs contain focal regions
      of 2-DG uptake in response to odor stimulation.

PMID- 7583340
TI  - Sex differences in interhemispheric correlation and spectral power of EEG
      activity.
AB  - EEG activity was recorded from left and right parietal cortex in adult male and
      female rats on a daily basis during 3 days. Absolute and relative power and
      interhemispheric correlation of the EEG activity were calculated and compared
      between males and females. Interhemispheric correlation of the theta rhythm was
      higher in males than in females. Interhemispheric asymmetry in absolute power was
      larger in males, who showed higher power in the right than in the left parietal
      for all bands except for delta. Beta2 relative power was significantly higher in
      females. These results indicate greater functional asymmetry and higher
      interhemispheric coupling of the parietal cortex in male than in female rats as
      assessed by cortical EEG activity.

PMID- 7583342
TI  - Filippo Pacini: a determined observer.
AB  - The life of Filippo Pacini (1812-1883) and his major scientific achievements are
      outlined. Pacini drew attention to the corpuscles named after him in 1831, when
      he was a medical student, and had to struggle for many years to convince the
      scientific community of the reliability and importance of his findings. In 1849
      Pacini became professor of anatomy at the University of Florence. Creative
      scientist, innovative teacher, well aware that the use of the microscope
      represented a revolutionary approach, Pacini pursued histological studies until
      his death. He also first discovered in 1854 (30 years before Robert Koch) the
      causative agent of cholera, and firmly believed that the disease was contagious.
      Strong-willed, modest, and poor, Pacini received from his colleagues more
      recognition in the obituaries than during his life.

PMID- 7583341
TI  - Further evidence that fluoxetine interacts with a 5-HT2C receptor in glial cells.
AB  - It is generally believed that the antidepressant drug fluoxetine (Prozac) exerts
      all its effects by inhibition of serotonin uptake into neurons and an ensuing
      increase in the extracellular concentration of serotonin. However, these studies
      have confirmed and expanded our previous observation that fluoxetine on its own
      exerts agonist effects on astrocytes (a glial cell type), which resemble those
      exerted by serotonin. Fluoxetine appears to act on a different subtype of
      receptor (the 5-HT2C receptor [in original terminology the 5-HT1C receptor]) than
      the one on which micromolar concentrations of serotonin are known to act in
      astrocytes (the 5-HT2A receptor [in original terminology the 5-HT2 receptor]).
      However, this study has shown that application of serotonin to these cells
      stimulates glycogenolysis and causes an increase in free cytosolic concentration
      of calcium that is not inhibited by the 5-HT2A selective antagonist, ketanserin.
      Moreover, both effects are pronounced at the low nanomolar level of serotonin
      and, therefore, by definition, act on the 5-HT2C receptor. The
      concentration/response correlation is identical for the serotonin effects on free
      cytosolic calcium concentration and on glycogenolysis. Fluoxetine exerts similar
      effects, but low nanomolar concentrations have no effect, and the concentration
      required to obtain half-maximum response is 1-3 microM, a concentration
      dependence that is consistent with the plasma levels of fluoxetine during
      treatment with this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583343
TI  - Interaction of serotonin and norepinephrine in spinal antinociception.
AB  - The interactions between different doses of serotonin (5-HT) and norepinephrine
      (NE) in in vivo experiments on rat spinal cord dorsal horn cells was investigated
      using the integrated electromyography (EMG) measurement of the nociceptive
      hindlimb flexor reflex (FR). The results indicate that (1) intrathecal (IT)
      administration of low doses of 5-HT (60 nmol) or NE (1.5 nmol) suppresses the
      nociceptive FR by 40% for 20 min, respectively; (2) administration of higher
      doses of 5-HT (240 nmol, IT) multiplies the suppression of the nociceptive FR by
      80% for 40 min, and NE (15 nmol, IT) produces similar suppression of the
      nociceptive FR for 80 min; (3) concomitant administration of low doses of 5-HT
      (60 nmol, IT) and NE (1.5 nmol, IT) produces a summation of the nociceptive FR
      suppression both in amplitude and duration; (4) concomitant administration of the
      higher doses of 5-HT (240 nmol IT) with NE (15 nmol, IT) produces similar effect
      obtained as 5-HT given separately, and no summation was obtained as observed
      following the lower dosages; (5) serotonin (240 nmol, IT) given 40 min before NE
      (15 nmol, IT) attenuates the duration of the suppression induced by NE; (6)
      pretreatment with a selective 5-HT2 receptor antagonist ketanserin (60 nmol, IT)
      failed to abolish the 5-HT effects; (7) pretreatment with ketanserin prior to
      concomitant administration of the higher doses of 5-HT and NE prolongs the time
      duration of the nociceptive FR suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583344
TI  - [3H]-noradrenaline release from streptolysin-O permeated rat cortical
      synaptosomes: enhancement of the Ca(2+)-induced signal.
AB  - We examined [3H]-noradrenaline ([3H]-NA) release from rat brain cortical
      synaptosomes permeated with streptolysin-O (SLO) under a variety of conditions.
      Three temperatures (20 degrees C, 25 degrees C, and 30 degrees C) were tested at
      different times of permeation. Lowering the incubation temperature to 20 degrees
      C decreased basal release, but Ca(2+)-induced [3H]-NA release increased slightly.
      Also, the incubation time to achieve the maximal ratio of Ca(2+)-induced release
      to basal release shifted to longer times with decreasing incubation temperature.
      If the synaptosomes were permeated with SLO before release was triggered, similar
      results were observed. Permeation at 20 degrees C allowed [gamma-32P] ATP and
      cAMP-dependent protein kinase (PKA) catalytic subunit to rapidly enter the
      synaptosomes to phosphorylate synapsins. Lactate dehydrogenase (LDH) efflux was
      time- and SLO-concentration dependent. The fact that 0.1 mM Cd2+ did not inhibit
      [3H]-NA release from permeabilized synaptosomes indicated that permeabilization
      by SLO was complete under these conditions. This also suggests that the release
      machinery involved after Ca2+ entry is not sensitive to Cd2+.

PMID- 7583346
TI  - An amino-terminal fragment peptide of acidic fibroblast growth factor modulates
      synaptic transmission in rat hippocampal slices.
AB  - Effects of acidic fibroblast growth factor (aFGF) fragments such as aminoterminal
      aFGF (1-15) and carboxyl-terminal aFGF (114-140) on synaptic transmission were
      investigated in rat hippocampal slices. Stimulation was applied to Schaffer
      collateral/commissural afferents, and evoked population spikes were recorded in
      the CA1 pyramidal cell layer. Continuous perfusion of slices with aFGF (1-15)
      slightly decreased the basal amplitude of population spikes and significantly
      increased the paired-pulse facilitation. When brief tetanic stimulation (7 pulses
      at 100 Hz) was applied 30 min after the perfusion of aFGF (1-15), aFGF (1-15)
      treated slices enhanced the magnitude of short-term potentiation after the
      tetanus and facilitated a generation of long-term potentiation. These effects of
      aFGF (1-15) were dose-dependent. Perfusion of slices with aFGF (114-140) had no
      effect on the basal spike amplitude, paired-pulse facilitation, and short-term
      potentiation. Both aFGF (1-15) and aFGF (114-140) had no effect on the DNA
      synthesis-stimulating activity in BALB/c 3T3-L1 cells. The results suggest that
      aFGF (1-15), which is not involved in mitogenic activity, is implicated in a
      modulatory mechanism of synaptic plasticity.

PMID- 7583345
TI  - Free D-serine concentration in normal and Alzheimer human brain.
AB  - We have analyzed both free L- and D-serine in frontal cortex of normal and
      Alzheimer human brain by high-performance liquid chromatography (HPLC). There was
      no significant difference between the two brains. In normal brain, L- and D
      serine concentrations were 666 +/- 222 and 66 +/- 41 nmol/g of wet tissue,
      respectively, and the ratio of D-isomer to L-isomer (D/L) was 0.099 +/- 0.031. In
      Alzheimer brain, the concentrations were 750 +/- 150 and 66 +/- 40 nmol/g,
      respectively, and the D/L ratio was 0.086 +/- 0.040. Thus, it was shown that the
      free D-serine concentration in the Alzheimer brain was comparable to that in the
      normal brain.

PMID- 7583347
TI  - Differences in Fos expression in the rat brains between cold and warm ambient
      exposures.
AB  - Fos expression in the rat diencephalon, brain stem, cerebellum, and spinal cord
      was examined after warm (33 degrees C) and cold (10 degrees C) ambient exposures.
      Fos expression was examined with use of immunohistochemical method and the number
      of Fos-positive neurons in each nucleus was quantitatively analyzed. When rats
      were exposed to cold ambient, significant number of Fos-positive neurons was
      found in the lateral septal nucleus (LS), preoptic hypothalamic area (POA),
      parvocellular paraventricular hypothalamic nucleus (pPVN), lateral preoptic area
      (LPO), zona incerta (ZI), paraventricular thalamic nucleus (PV), ventromedial
      hypothalamic nucleus (VMH), subparafascicular thalamic nucleus (SPF), posterior
      hypothalamic area (PH), supramammillary nucleus (SuM), microcellular tegmental
      nucleus (MiTg), lateral lemniscus nucleus (LL), lateral dorsal central grey
      (CGLD), lateral ventral central grey (CGLV), dorsal parabrachial nucleus (DPB),
      locus coeruleus (LC), dorsal tegmental nucleus (DTg), vestibular nucleus (Ves),
      nucleus of solitary tract (Sol), spinal cord, and cerebellum. When animals were
      exposed to warm ambient, the numbers of Fos-positive neurons in the LS, POA, PV,
      LPO, and SuM were significantly increased to be equal to those of cold ambient.
      However, after warm ambient exposure the numbers of Fos-positive neurons in the
      DPB and spinal cord were increased but less than those of cold ambient, and those
      in the pPVN, VMH, ZI, SPF, PH, CGLD, CGLV, MiTg, LL, LC, DTg, Ves, Sol, and
      cerebellum were not significantly increased as compared with those of control or
      cold ambient. Abdominal temperature was not changed during cold ambient exposure,
      but the temperature was significantly increased during warm ambient
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583348
TI  - Chronic administration of L-NAME in drinking water alters working memory in rats.
AB  - To examine the role of nitric oxide (NO) in the maintenance of working memory of
      rats, the effects of chronic administration (in drinking water) of the NO
      synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), on this
      behavior was examined with a simple test of remembering recently explored
      objects. Unlike other working memory tasks that require a subject to perform for
      a reward such as food or water or to avoid shock, our task measured spontaneous
      exploration of novel and familiar objects and has been described as a "pure"
      working memory task [9]. Normal subjects spend significantly more time in contact
      with new environmental components and less time with familiar objects. A subject
      that extensively reexplores a stimulus with which it has previous experience is
      presumed to exhibit some memory loss associated with the object. Memory changes
      were evaluated by measuring the relative time subjects explored familiar versus
      new stimulus objects. Rats (n = 15) that chronically drank L-NAME (approximately
      90 mg/kg/day) for 14 days spent significantly less time exploring a novel object
      than did rats (n = 13) that drank only tap water (p < .05). This effect of L-NAME
      was abolished by concurrent administration of L-Arginine (approximately 4.5
      g/kg/day). Total object exploration was not affected by our drug treatments,
      suggesting that our object discrimination task is not activity dependent. These
      data are consistent with the hypothesis that NO is required for some forms of
      working memory.

PMID- 7583349
TI  - Genetics of tumour necrosis factor-alpha in autoimmune, infectious, and
      neoplastic diseases.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is a potent immunomediator and
      proinflammatory cytokine that has been implicated in the pathogenesis of a large
      number of human diseases. The location of its gene with the major
      histocompatibility complex and biological activities have raised the possibility
      that polymorphism within this locus may contribute to the genetic association of
      this region of the genome with a wide range of autoimmune and infectious
      diseases. This review discusses the genetics of the TNF locus in several of the
      major autoimmune diseases and also in relation to infectious and neoplastic
      diseases. There is increasing evidence that genetic variation within the TNF
      locus is important in determining susceptibility to, or severity of, a
      significant number of these conditions.

PMID- 7583351
TI  - Genetic dissection of inflammatory responses.
AB  - Recent advances in classical genetics, molecular biology, and genomics herald a
      renaissance of genetic analysis of hereditary disease in both humans and animal
      models. It is increasingly feasible to analyze multifactorial traits both
      genetically and functionally. These advances parallel research aimed at
      unravelling the genetic code of humans and model species. Only the integration of
      these two approaches will secure the functionally significant conclusion of the
      genomic exercise.

PMID- 7583350
TI  - Molecular mechanism in tolerance to lipopolysaccharide.
AB  - Stimulation with lipopolysaccharide (LPS) will lead to the expression of a
      variety of genes in CD14+ monocytes/macrophages, but also in CD14- fibroblasts
      and endothelial cells. Upon secondary LPS stimulation, the expression of many of
      these genes is only minimal. This applies to several cytokines, most prominent
      among them tumor necrosis factor (TNF). Induction of tolerance appears to require
      some degree of activation in the primary exposure, as partial structures of LPS
      induce tolerance, as long as they are able to activate cells. Studies on the
      mechanism of unresponsiveness in tolerant cells show that the CD14 LPS receptor
      is not downregulated but may even increase in number at the cell surface.
      Furthermore, this receptor appears to be functional in that mobilization of the
      transcription factor NF-kappa B does still occur. This NF-kappa B complex is
      composed primarily of p50p50 homodimers, that bind to the respective DNA motif in
      the promoter region of many proinflammatory genes, thereby blocking
      transactivation. However, LPS tolerance does not lead to downregulation of all
      kinds of response, as some genes are even increased in expression upon secondary
      stimulation; these include p50 of NF-kappa B, TNF receptor type II and
      interleukin-10 (IL-10). These gene products are involved in the downregulation of
      proinflammatory cytokines and may thereby be instrumental in the unresponsiveness
      observed. Hence, tolerance to LPS is not a passive process that occurs in an
      exhausted cell; rather, it is a well-controlled active response that is
      orchestrated in order to prevent excessive inflammation. Important modulators of
      tolerance are glucocorticoids, which result in a general decrease of gene
      expression, and interferon-gamma (IFN-gamma), which enhances expression of
      proinflammatory genes. LPS tolerance does occur in some clinical settings, as in
      hemodialysis, in sepsis and in patients treated repeatedly with LPS or other
      monocyte activators. In fact, LPS tolerance may be exploited for prophylaxis of
      severe sepsis in patients at risk.

PMID- 7583352
TI  - Tumor necrosis factor-alpha and interleukin-1 beta mediate human endothelial cell
      activation in blood at low endotoxin concentrations.
AB  - Activation of endothelial cells by endotoxin (lipopolysaccharide, LPS) may occur
      through two different pathways. LPS can directly activate endothelial cells
      through its interaction with soluble CD14 or indirectly via cytokines produced in
      blood in response to LPS. Substitution of whole blood for plasma apparently
      increases the endothelial cells responses to LPS by a factor of 1,000, rendering
      them sensitive to subpicomolar quantities of LPS. This shift in sensitivity is
      dependent on the presence of monocytes or conditioned plasma from whole blood
      incubated with small concentrations of LPS. Herein, using agents that block the
      effects of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1
      beta), we demonstrate that TNF-alpha and IL-1 beta are the two LPS-induced
      cytokines responsible for the activation of endothelial cells, produced in blood
      in response to picomolar quantities of LPS. Anti-TNF-alpha monoclonal antibodies
      (mAbs) and IL-1 receptor antagonist separately had partial inhibitory effects.
      Complete and sustained inhibition of endothelial cell activation was obtained
      only when the two inhibitors were added together. We conclude that TNF-alpha and
      IL-1 beta induced in whole blood by picomolar concentrations of LPS mediate
      endothelial cell activation to these small quantities of LPS and that blocking of
      both cytokines is necessary to inhibit LPS-induced blood-dependent endothelial
      cell activation.

PMID- 7583354
TI  - Nuclear migration of NF-kappa B correlates with TNF-alpha mRNA accumulation.
AB  - Previous work on the transcriptional regulation of the mouse TNF-alpha promoter
      had indicated a major role for the NF-kappa B transcription factor in the
      induction of the gene by endotoxin. However, similar studies using the human
      promoter failed to establish a role for this factor. We measured the nuclear
      migration of NF-kappa B and the accumulation of TNF-alpha mRNA in murine T
      lymphoblasts and bone marrow-derived macrophages (BMDM) under different
      activation conditions, seeking to establish a correlation. Activation of NF-kappa
      B and accumulation of TNF-alpha mRNA correlated semiquantitatively under the
      following conditions: (1) inhibition of NF-kappa B by dithiocarbamates; (2)
      induction of TNF synthesis by taxol; (3) partial induction of TNF-alpha mRNA by
      various inducers in macrophages from lpsd mice; and (4) inhibition of NF-kappa B
      activation by a protease inhibitor. However, inhibition of TNF-alpha mRNA
      accumulation by cAMP inducers had no effect on NF-kappa B induction. We conclude
      that NF-kappa B translocation is necessary, but not sufficient for the
      transcriptional induction of the TNF-alpha gene by LPS in macrophages or by
      phorbol ester and ionomycin in T lymphocytes.

PMID- 7583353
TI  - Interleukin-10 is upregulated in LPS tolerance.
AB  - Lipopolysaccharide (LPS) stimulation of the human monocytic cell line Mono Mac 6
      leads to rapid expression of both the pro-inflammatory cytokine tumor necrosis
      factor (TNF) and the anti-inflammatory cytokine interleukin-10 (IL-10).
      Preculture of these cells with a low dose of LPS for 2 days rendered the cells
      tolerant to subsequent stimulation, in that TNF gene expression is only minimal,
      both at the mRNA and at the protein level. IL-10 shows a reciprocal pattern,
      however, as expression of this gene is upregulated in precultured cells, and it
      will further increase upon subsequent stimulation. Although TNF has been shown to
      induce IL-10, and IL-10 was found to downregulate TNF, this reciprocal regulation
      does not explain the pattern observed in LPS tolerance in Mono Mac 6, since
      neutralizing antibodies against TNF and IL-10 could not prevent upregulation of
      IL-10 and downregulation of TNF, respectively. Treatment of Mono Mac 6 cells
      during LPS preculture with interferon-gamma (IFN-gamma) could, however, reverse
      tolerance: LPS/IFN-gamma precultured cells produced high levels of TNF
      transcripts upon subsequent stimulation, while the response of the IL-10 gene was
      attenuated. The data show that LPS tolerance does not involve a passive
      downregulation of all types of monocyte functions, but it is an orchestrated
      response with downregulation of pro- and upregulation of anti-inflammatory
      cytokines.

PMID- 7583355
TI  - Absence of lymph nodes in lymphotoxin-alpha(LT alpha)-deficient mice is due to
      abnormal organ development, not defective lymphocyte migration.
AB  - Mice homozygous for a targeted null mutation of lymphotoxin-alpha (LT alpha) are
      born without lymph nodes (LN) or Peyer's patches (PP) and with altered splenic
      architecture. To investigate the mechanism of failed LN organogenesis, we
      transferred bone marrow (BM) from Thy 1.2 LT alpha-deficient or Thy 1.2 wild type
      mice to lethally irradiated 8-12-week-old Thy 1.1 wild type recipients. Six to 10
      weeks later, reconstitution of LN and spleen with Thy 1.2 cells was similar
      whether the BM was derived from LT alpha-deficient or wild type donors. In
      contrast, reconstitution of irradiated LT alpha-deficient mice with wild type BM
      did not induce the development of detectable LN, although reconstitution of the
      spleen occurred appropriately. The expression and regulation of the lymphocyte
      adhesion molecule L-selectin from the LT alpha-deficient mice appeared normal.
      These data indicate that LT alpha-dependent interactions must occur during
      development in order for LN genesis to take place; however, lymphocyte expression
      of LT alpha is not required for these cells to home to existing LN structures.

PMID- 7583356
TI  - Comparative expression of TNF-alpha alleles from normal and autoimmune-prone MHC
      haplotypes.
AB  - The tumor necrosis factor-alpha (TNF-alpha, or TNF) genes of NOD mice and NZW
      mice are reportedly underexpressed relative to the TNF genes of control mice in
      lipopolysaccharide (LPS)-induced peritoneal macrophages. These findings, as well
      as the well-known major histocompatibility complex (MHC) linkage of the TNF
      genes, have prompted speculation that mutations affecting expression of the TNF
      alpha loci might represent a primary cause of autoimmune diseases. Differences in
      expression of the TNF genes in different strains of mice might result either from
      effects of cis-acting mutations or from differences in the cellular environment
      that operate in trans. To discriminate between these possibilities, we directly
      examined the relative contribution made by each of two different TNF alleles (one
      associated with an autoimmune-prone haplotype and the other not) to the pool of
      TNF mRNA within the cells of F1 hybrid mice. Reverse transcription-polymerase
      chain reaction (RT-PCR) was used to amplify a polymorphic fragment derived from
      the total pool of TNF mRNA present in LPS-induced peritoneal macrophages of
      hybrid animals produced by crossing BALB/c to non-obese diabetic (NOD), and New
      Zealand black (NZB) to New Zealand white (NZW). In both types of F1 hybrid, the
      two alleles were represented in nearly equal quantities at the mRNA level. It may
      be inferred that at all pretranslational levels, the NZW and NOD TNF alleles are
      functionally equivalent to the control alleles that were examined. Interstrain
      differences in responsiveness to LPS are therefore responsible for interstrain
      differences in TNF gene expression.

PMID- 7583357
TI  - LPS-dependent interaction of Mac-2-binding protein with immobilized CD14.
AB  - CD14 is a glycosylphosphatidyl-inositol (GPI)-linked, 55 kDa protein that binds
      bacterial lipopolysaccharide (LPS, endotoxin) and plays a key role in mediating
      cellular responses to this potent inflammatory stimulus. Binding of LPS to CD14
      is facilitated by serum proteins such as LPS binding protein (LBP). To determine
      if there are additional plasma proteins that bind to CD14, plasma was passed over
      immobilized CD14 in the presence or absence of LPS, and retained proteins were
      eluted. This procedure isolated not only LBP but also a serum protein known as
      Mac-2-binding protein (Mac-2-BP), a 97 kDa species without a known function.
      Binding of both LBP and Mac-2-BP to CD14 required the simultaneous presence of
      LPS. Experiments with purified Mac-2-BP showed that this protein alone neither
      enabled responses of CD14-bearing cells to LPS nor blocked the ability of plasma
      to enable responses of CD14-bearing cells to LPS. However, Mac-2-BP did slow the
      neutralization of LPS mediated by plasma lipoprotein. These studies describe the
      first potential function for Mac-2-BP, and suggest that neutralization of LPS in
      plasma may be controlled by proteins in addition to LBP and CD14.

PMID- 7583358
TI  - RAW264 macrophages stably transfected with an HIV-1 LTR reporter gene provide a
      sensitive bioassay for analysis of signalling pathways in macrophages stimulated
      with lipopolysaccharide, TNF-alpha or taxol.
AB  - Bacterial lipopolysaccharide (LPS) modulates expression of a variety of genes in
      macrophages, and additionally activates viral promoters including the HIV-1 LTR.
      The HIV-1 LTR driving the luciferase reporter gene was stably transfected into
      the murine macrophage cell line, RAW264. In stably transfected cells, luciferase
      activity was LPS-dependent. As little as 0.01 ng/ml LPS was sufficient to
      increase luciferase activity over basal levels with maximal stimulation resulting
      in a 10- to 20-fold response. The cells also responded to human and murine tumour
      necrosis factor (TNF alpha). Endogenous TNF alpha was not involved in LPS
      responses, since pretreatment with alpha-TNF alpha antibody did not affect
      activation. Induction of HIV-1 LTR activity by LPS occurred independently of
      phorbol myristate acetate (PMA) sensitive protein kinase C (PKC), since depletion
      of PKC by prolonged exposure to PMA blocked TNF alpha and PMA responses but was
      not able to abolish LPS action on these cells. Taxol (5-20 micrograms/ml), a
      chemotherapeutic agent which mimics LPS action on macrophages, was also able to
      increase expression of the reporter gene driven by the HIV-1 LTR. However, lower
      doses of taxol that were not sufficient to trans-activate the LTR or to induce
      TNF alpha expression were cytotoxic to RAW264 cells suggesting that the cytotoxic
      and LPS-like activities of taxol were not linked. This cell line provides a
      convenient method for detecting LPS-like activity and is a useful tool for
      examining LPS and TNF alpha signalling pathways.

PMID- 7583360
TI  - Gaining insights into the ontogeny and activation of T cells through the use of
      gene-targeted mutant mice.
AB  - T lymphocytes recognize peptides bound to major histocompatibility complex
      products through the alpha- and beta-chains of their T-cell antigen receptors
      (TcR). The interaction between T cells and target cells or antigen-presenting
      cells is also assisted by a series of other accessory cell surface proteins.
      Probably most characterized of these accessory molecules are CD4 and CD8, which
      are differentially expressed on helper and cytotoxic T-cell lineages,
      respectively. Upon engagement of ligands by these cell surface proteins, a series
      of signals are transduced intracytoplasmically via associated protein kinases,
      such as the lymphocyte-specific tyrosine kinase lck. Another component important
      to signaling is the cell surface tyrosine phosphatase CD45, which through
      alternative splicing occurs in different isoforms on various hematopoietic and
      lymphopoietic cells. Despite the complexity of the TcR, signals generated via
      these receptors are thought to be insufficient to fully activate T lymphocytes.
      Many investigators believe that collateral (costimulatory) signaling of the CD28
      molecule and the TcR facilitates complete activation of T lymphocytes. In
      addition, immune responses are regulated by a number of cytokines and soluble
      factors. Finally, at a very basic level, transcriptional factors, such as those
      involved in controlling interferon production, are important in T-cell
      development and immune responses. In an attempt to better understand the roles of
      these molecules in T lymphocyte function and ontogeny, we generated a series of
      mutant mice with disruptions in the genes coding for these molecules. The
      following discussion reports on some of the findings observed with these mutant
      animals.

PMID- 7583359
TI  - Plasma interleukin 8 and polymorphonuclear leukocyte elastase concentrations in
      patients with septic shock.
AB  - We determined the plasma concentrations of interleukin 8 (IL-8),
      polymorphonuclear leukocyte elastase (PMNE), and endotoxin in patients with
      septic shock in order to investigate the role of IL-8 and PMNE in the development
      of septic shock, especially in septic adult respiratory distress syndrome (ARDS).
      The IL-8 concentration in patients with septic shock was 6.28 +/- 9.00 ng/mL
      (mean +/- SD, n = 29), which was significantly higher (P < 0.0001) than the
      concentration in septic patients without shock (0.35 +/- 0.35 ng/mL, n = 40).
      There was a significant correlation between the IL-8 concentration and the PMNE
      concentration at the onset of septic shock (r = 0.6916, P < 0.0001). The IL-8
      concentration was also significantly correlated with the endotoxin concentration
      (r = 0.5584, P = 0.0016). There was a significant negative correlation (r = 
      0.8237, P < 0.0001) between the serum PMNE concentration and the oxygenation
      index (PaO2/FiO2) at the onset of septic shock. These results indicate that IL-8
      and PMNE are produced in large quantities when septic shock occurs, and may play
      a role in the development of septic ARDS.

PMID- 7583363
TI  - Surgery of astrocytomas in the motor and premotor cortex under local anesthesia:
      report of 11 cases.
AB  - Under local anesthesia, gliomas of the premotor and primary motor cortex can be
      surgically removed with minimal morbidity. However, since these neoplasms exhibit
      an infiltrative growth pattern towards the pyramidal tract and are frequently not
      well delineated from functional motor cortex, the long-term outcome is
      unfavorable. In this series, 5 of 11 patients presented with a recurrent tumor
      within two years of operation. Two of these patients with recurrent tumors
      initially had a low grade glioma and three an anaplastic glioma. Due to the
      longer progression-free interval after surgery and the unpredictable course of
      patients with low grade gliomas, all efforts should be undertaken to achieve safe
      and radical resection with the use of intraoperative mapping and monitoring
      techniques as well as cryo-cut examinations at all tumor border zones to prove
      radicality. Since malignant tumors are known to recur in most instances, radical
      resection is justified only in functionally safe areas.

PMID- 7583362
TI  - Mechanism of action of bicyclic imidazoles defines a translational regulatory
      pathway for tumor necrosis factor alpha.
AB  - Expression of tumor necrosis factor alpha (TNF) by lipopolysaccharide-treated
      human monocytic cells is inhibited by bicyclic imidazoles. We studied the
      mechanism of action of a representative inhibitor, SK&F 86002, on synthesis of
      TNF by THP-1 cells. Levels of TNF protein were lowered by SK&F 86002 under
      conditions where TNF mRNA accumulation was unaffected, suggesting a post
      transcriptional action. No effect of SK&F 86002 was detected on the rate of
      induction of TNF mRNA or steady state levels over a 5 hr period. The kinetics of
      SK&F 86002 inhibition of TNF protein synthesis coincided with those of
      anisomycin, not with actinomycin, suggesting an effect of SK&F 86002 on TNF mRNA
      translation. By using sucrose gradient sedimentation, we showed that quiescent
      THP-1 cells contained a substantial amount of TNF mRNA which was primarily
      associated with 43S pre-ribosomal complexes. Activation of the cells with
      lipopolysaccharide caused an elevation of the TNF mRNA level and increased the
      proportion associated with polyribosomes. Treatment with lipopolysaccharide plus
      SK&F 86002 led to a marked accumulation of TNF mRNA in the 43S complex-containing
      fractions and a concomitant reduction of polysome-associated TNF message. Neither
      lipopolysaccharide nor SK&F 86002 affected the amount or distribution of
      cyclophilin mRNA in the same fractions. The results suggest that
      lipopolysaccharide activates TNF translation at the initiation step and that SK&F
      86002 inhibits this activation.

PMID- 7583361
TI  - Malaria-specific metabolite hemozoin mediates the release of several potent
      endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered
      thermoregulation in vivo.
AB  - A characteristic feature of malaria infection is the occurrence of periodic bouts
      of fever. Experimental and clinical studies have strongly implicated inflammatory
      cytokines, like tumour necrosis factor (TNF), in the induction of these
      intermittent fevers [Clark et al., Infect Immunol 32:1058-1066, 1981; Clark et
      al., Am J Pathol 129:192-199, 1987; Karunaweera et al., Proc Natl Acad Sci USA
      89:3200-3203, 1992], but the malaria-specific metabolite(s) which induce the
      production of such endogenous pyrogens have not yet been fully characterized. It
      is well known that during the course of malaria infection, a unique schizont
      component, alternatively referred to as "malaria pigment" or hemozoin, is
      released along with merozoites as the host erythrocyte bursts [Urquhart, Clin
      Infect Dis 19:117-131, 1994]. We have recently determined that the core structure
      of hemozoin comprises a novel insoluble polymer of heme units linked by iron
      carboxylate bonds [Slater et al., Proc Natl Acad Sci USA 88:325-329, 1991; Slater
      et al., Nature 355:167-169, 1992]. We now report that purified native, as well as
      chemically synthesized, hemozoin crystals potently induce the release of several
      pyrogenic cytokines, including TNF, MIP-1 alpha, and MIP-1 beta, from murine
      macrophages and human peripheral blood monocytes in vitro. Also, intravenous
      administration of chemically synthesized preparations of hemozoin to
      anaesthetized rats results in a marked drop in body temperature. A similar drop
      in body temperature is observed following the intravenous injection of other well
      characterized pyrogenic cytokines (e.g., TNF) which are known to induce a fever
      response in awake animals, and is thought to reflect the inability of rats to
      appropriately regulate their body temperature while anaesthetized. As a
      consequence of its ability to induce pyrogenic cytokines in vitro, and thermal
      dysregulation in vivo, we propose that this unique parasite metabolite is an
      important pyrogen released by malaria parasites at schizogomy, which acts by
      eliciting the production of a group of potent endogenous pyrogens, which include
      MIP-1 alpha and MIP-1 beta, as well as TNF, in macrophages.

PMID- 7583364
TI  - Stereotactically-guided microsurgical resection of deep-seated brain lesions:
      minimization of established and development of new unconventional approaches.
AB  - Since April 1987 we have operated upon 209 patients with deep-seated or
      subcortically located lesions of differing etiology utilizing stereotactical
      microresection techniques in conjunction with the Dortmunder microstereotactic
      device. By means of these techniques the size and subsequent trauma of
      established surgical approaches were minimized; the approaches could be chosen
      more selectively according to lesion-situs and the functional topographic
      anatomic considerations enroute; additionally, new, unconventional,
      transparenchymal, low-trauma approaches were adopted. A survey of our concept of
      minimal invasive neurosurgery stemming from the utilization of stereotactic
      microresection techniques with approach optimization and modification is
      presented.

PMID- 7583365
TI  - Endoscopic management of craniopharyngiomas: a review of 3 cases.
AB  - The authors describe the endoscopic management of cystic craniopharyngiomas in 3
      cases. This method has been attempted in cystic craniopharyngiomas using a rigid
      endoscope. The instrument has been described earlier (7-9). All these operations
      were done under general anaesthesia. Criteria for endoscopic extirpation and
      removal included type D, E, F classification according to Yasargil (17). All 3
      cases fitted in the F category. There were one female and two male patients. In
      the female patient an aspiration of cyst contents was performed as a first
      attempt to relieve her hydrocephalus. Two months later recurrent symptomology
      necessitated a larger intervention. All cysts were opened using the laser,
      drained by a Fogarthy balloon-catheter, and the capsule removed by forceps. This
      technique is safe and provides a reasonable alternative to open microsurgery,
      radioactive isotope instillation, or radiotherapy. In our series we achieved
      total removal in one case after the second intervention and partial removal in
      two cases. There was no mortality directly associated with this procedure and the
      female patient developed severe electrolyte disturbances after macroscopic total
      removal. Our results suggest that endoscopic of management of cystic
      craniopharyngiomas is a safe and effective procedure which could be considered as
      the initial management for cystic craniopharyngiomas of the intraventricular
      type.

PMID- 7583366
TI  - Endoscopic-image display system mounted on the surgical microscope.
AB  - This report describes a newly developed endoscopic-image display system which is
      mounted on the optical unit of the surgical microscope. This system permits the
      neurosurgeon to watch the endoscopic image through one of the eye lenses of a
      surgical microscope during application of neurosurgical endoscopy under open
      microsurgical procedures. It frees the neurosurgeon from the major conventional
      inconvenience that he has to discontinue watching the microscopic view in order
      to look at the endoscopic images through the ocular of the endoscope or on the
      video monitor.

PMID- 7583368
TI  - Percutaneous anterior discectomy under ultrasound guidance.
AB  - The object of this experiment was to demonstrate that, by using a peritoneal
      fluid infusion coupled with ultrasound guidance, a safe anterior entry into the
      L5-S1 disc of the pig could be made. The goal was to develop a procedure with the
      advantages of a laparoscopic approach to the disc which has been published to
      allow removal of extruded herniations, that a neurosurgeon could perform without
      a general surgeon in attendance. The procedure was carried out under general
      anesthesia and fluoroscopic control. One liter of normal saline was then infused
      into the abdomen of a pig. Under ultrasound guidance and laparoscopic
      confirmation, a Nucleotome was placed into the L5-S1 disc and the disc was
      aspirated. The results showed that the disc was safely entered in all 5 pigs. The
      disc was successfully removed in 4 of 5 pigs. In all animals the bowel floated
      out of the pelvis, obviating the need for bowel manipulation. Laparoscopic
      ultrasound was needed for visualization in 3 pigs, while external ultrasound was
      used in two. Our conclusion is that peritoneal fluid infusion and ultrasound
      guidance, when applied to laparoscopic anterior discectomy, eliminates the need
      for retroperitoneal dissection and bowel manipulation, significantly simplifying
      the laparoscopic discectomy procedure.

PMID- 7583369
TI  - A simple steady state model of the distribution of vertical temperature in
      broiler houses without internal air circulation.
AB  - 1. The vertical temperature profile in a broiler house depends on several
      factors: ground temperature, heat production by the birds, heating of litter by
      resting birds, stratification and radiation, microbial heat production in the
      litter, moisture loss from litter and natural convection around the birds. The
      effect on the vertical temperature profile is calculated for each factor and the
      effects are finally combined to estimate vertical temperature distribution. 2.
      The vertical temperature profile in a commercial broiler house depends on the age
      of the birds. Influential factors for young broilers are ground temperature and
      stratification. For older broilers, influential factors are floor construction
      and ground-water table, heat production of broilers and litter, the behaviour of
      the broilers and air circulation in the house. 3. Temperatures in the living zone
      can differ appreciably, by a maximum of about 4 degrees C, from mean house
      temperature. 4. The velocity of air induced by the heat production of the
      broilers is about 5 cm/s. This provides good air mixing in the living zone.

PMID- 7583367
TI  - Localization of superficial cerebral lesions using a magnetic resonance imaging
      guided localizer.
AB  - The localization of superficial cerebral lesions may be difficult even if they
      reach the surface of the cerebral cortex. Intraoperative ultrasound often fails
      to detect subcortical lesions. A localization device using multiplanar MR-imaging
      has been designed to project such lesions to the scalp. This device is a hood
      shaped grid made of polyethylene tubing filled with paramagnetic contrast agent.
      In this hemispherical grid the tubes are arranged at a distance of 15 to 30 mm so
      that the MR-plane always slices perpendicular to the axis of the tubing and
      depicts a bright spot per tube. It is rapidly filled prior to each MR
      examination, placed on the patient's head, and taped to his forehead to avoid
      unintentional displacement during and after the examination until the projection
      of the lesion is marked on the skin.

PMID- 7583370
TI  - Food intake and growth in chickens given food in the wet form with and without
      access to drinking water.
AB  - 1. Individually caged growing chickens were offered a commercial grower food
      mixed with 1.5 to 2.25 times the weight of water and the effects, compared to
      giving the same food in air-dry form, on food intake, body weight gain and
      carcase composition were investigated. 2. Male broilers (24) were given either a
      grower food in the air-dry form with access to drinking water or the same food
      mixed with 2.0 parts of water (700 g water/kg of mixed food) with no drinking
      water from 28 to 49 d of age. From 49 to 63 d all birds were given dry food and
      drinking water and were then killed for carcase analysis. Food intake and weight
      gain were significantly increased during the wet-feeding period, as was carcase
      protein but not abdominal or carcase fat at the end of the experiment. 3. Five
      male broilers were given each of 5 dietary treatments containing 0 (control),
      1.5, 1.75, 2.0 and 2.25 times added water (640, 673, 700 and 723 g water/kg) from
      28 to 49 d. Food intakes, body weight gains and carcase weights were
      significantly increased for all water additions compared with dry food, but there
      were no significant differences between different water additions. 4. Female
      broiler chicks responded to wet feeding (700 g water/kg) in a similar manner to
      males and the dry matter approximate digestibility was increased from 0.65 for
      the dry food to 0.73 for the wet. 5. Cockerels of an egg-laying strain did not
      increase their intake of dietary dry matter when it was fed in the wet form (700
      g water/kg), but there was a significant increase in body weight gain. 6. Male
      broilers were offered wet food (700 g water/kg) with or without access to
      drinking water. There was equal stimulation of food intake, growth and carcase
      weight with both wet-feeding treatments. 7. Providing food mixed with sufficient
      water to give a porridge-like consistency significantly increased weight gains in
      each of the five experiments and significantly improved food conversion
      efficiency in three of the five. It is not necessary to withhold drinking water
      in order to obtain this effect.

PMID- 7583371
TI  - The role of ion transport in the formation of sub-embryonic fluid by the embryo
      of the Japanese quail.
AB  - 1. Using a modification of the method of New (1955) explanted blastoderms of the
      Japanese quail were cultured for up to 72 h, and the role of ions in the
      formation of sub-embryonic fluid (SEF) investigated. 2. Culture media deficient
      in either sodium or chloride ions reduced the volume of SEF secreted by up to a
      quarter. Ionic composition of the fluid was little altered, and sodium was
      transported against a concentration gradient. 3. Amiloride, an inhibitor of
      Na+/H+ exchange, reduced SEF production by half, whereas ionic composition and
      osmolality of the fluid was unchanged. 4. Likewise, acetazolamide, an inhibitor
      of carbonic anhydrase, reduced SEF production by the blastoderm, and left the
      ionic composition and osmolality of the fluid unaltered. 5. Neither furosemide or
      4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid at the concentrations used
      changed the volume of SEF formed or its ionic composition. 6. It is concluded
      that the secretion of SEF is dependent upon the active transport of sodium across
      the blastoderm; an amiloride-sensitive Na+/H+ exchanger and carbon dioxide
      hydration catalysed by carbonic anhydrase are also involved. 7. Furthermore, it
      is proposed that fluid transport across the blastoderm is the result of local
      osmotic gradients, not from a sub-embryonic fluid hyperosmotic to albumen, as has
      been suggested previously.

PMID- 7583373
TI  - Incremental changes in and distribution of chick weight with hen age in four
      poultry species.
AB  - 1. It is proposed that a general biological pattern exists for chick weight
      increase with hen age for the various commercial species of poultry and that one
      general equation can be used for the estimation of chick weight increment. 2. The
      parameters estimated for this equation are based on (a) chick weights as a
      percentage of annual mean chick weight, and (b) age, from onset of lay, as a
      percentage of maximum age of the hen; both serving as common denominators. Hence,
      if the annual mean chick weight is known for any species, breed or strain, then
      the increase in chick weight can be predicted for the whole season, or for any
      particular hen age. 3. For early prediction, first-month chick weight can be used
      to estimate the annual mean weight and consequently the chick weight curve for
      the full season. Although such prediction will be somewhat less accurate, it
      still can be used for general planning. 4. Results indicate that chick weights of
      various avian species are normally distributed. Therefore, at each point of hen
      age, the chick weight distribution can be estimated by employing the computerised
      Burr's (1967) equation. This may be useful for segregating chicks by size, thus
      improving uniformity and reducing competition within the flock. 5. Computation
      results show that coefficient of variation (CV) of chick weights, originating
      from 22 and 62 week dam ages, is increased by up to about 75%. The CV may thus be
      used as a quality indicator.

PMID- 7583372
TI  - The effect of varying dietary concentrations of vitamin A on immune response in
      the turkey.
AB  - 1. The effect of dietary vitamin A on antibody production and T-cell
      proliferative response was determined in poults from 21 to 41 d old. Poults were
      fed on soyabean meal-sorghum-based diets with concentrations of supplemented
      vitamin A from 0 to 13.2 micrograms/g retinol equivalents from hatching and were
      immunised with Newcastle disease virus (NDV) and turkey pox vaccines. T-cell
      proliferation response to concanavlin A was determined in vitro at 31 d old.
      Antibodies to NDV and turkey pox in serum were determined at 10 and 20 d after
      inoculation. 2. Poults receiving the diet with no added dietary vitamin A died by
      22 d and had very low concentrations of plasma and liver vitamin A. 3. Increasing
      dietary concentrations of vitamin A enhanced the proliferative response until the
      diet contained 6.0 micrograms/g, above which the response began to decrease. The
      antibody titres to NDV and turkey pox increased as dietary vitamin A increased,
      with maximal values found 10 d after inoculation with 6.0 micrograms/g. At 20 d
      after inoculation low antibody titres were found with low vitamin A intake. 4.
      These data suggest that maximal immune responses in the poult may be achieved at
      dietary intakes of vitamin A at or higher than those recommended by NRC (1984,
      1994).

PMID- 7583375
TI  - Histopathological alterations of turkey skeletal muscle observed at the
      slaughterhouse.
AB  - 1. Six leg muscles (iliotibialis cranialis, iliotibialis lateralis, flexor cruris
      lateralis pars pelvica, gastrocnemius lateralis, gastrocnemius medialis and
      puboischiofemoralis medialis) were collected immediately after slaughter from
      each of 200 randomly selected male commercial turkeys. 2. Among these 1,200
      samples processed for histology and examined in cross-sections, 9.4% exhibited
      fibre splitting and 9% intrafascicular adipose tissue infiltration. 3.
      Gastrocnemius medialis muscles were more often affected than other muscles (P <
      0.05), with 33% showing isolated necrotic fibres. There were rarely more than 5
      necrotic cells out of roughly 4000 cells per sample. 4. Twelve percent of samples
      showed a high incidence of hypercontracted fibres, 63% a medium incidence (less
      than 8% present) and 24% none. Hypercontraction was more frequent in
      puboischiofemoralis medialis muscles (P < 0.05).

PMID- 7583374
TI  - Irradiation-induced off-odour in chicken and its possible control.
AB  - 1. Volatiles isolated from irradiated raw chicken were analysed by gas
      chromatography (GC) in conjunction with olfactory assessment of the effluent
      carrier gas to locate compounds with strong smells. 2. Sixteen odours of
      differing intensities were registered, some, but not others, coinciding with
      recognisable GC peaks. Identifications were made on the basis of retention data,
      mass spectrometric information and odour quality agreement. 3.
      Dimethyltrisulphide was found to be the most potent and obnoxious compound (foul
      gas, sulphurous), followed by cis-3- and trans-6-nonenals (soapy), oct-1-en-3-one
      (mushroom) and bis(methylthio-)methane (foul). With the exception of oct-1-en-3
      one, none of these compounds has been reported before in irradiated raw chicken.
      4. alpha-Tocopherol and ascorbic acid induce stability in tissues in vivo and
      post mortem. Chickens were reared on diets supplemented with high concentrations
      (800 mg/kg food) of each of these vitamins. Yields of irradiation volatiles from
      the tissues of these birds were very much reduced, compared to yields from
      similar tissues from birds fed unsupplemented diets. 5. Concomitantly with the
      reduced yield of volatiles, less odour was associated with the samples when
      analysed by GC-olfactory analysis. 6. The use of enhanced concentrations of the
      two vitamins in combination in the diet of poultry may provide a means of
      controlling development of off-odour in irradiated raw chicken, thus improving
      acceptability to the consumer.

PMID- 7583376
TI  - Influence of subclinical virus infections and other factors on broiler flock
      performance.
AB  - 1. The influence of subclinical infections with infectious bursal disease virus,
      adenoviruses, REO viruses and chicken anaemia virus and of various production
      variables on broiler flock performance was investigated. 2. A significant effect
      could not be demonstrated of any of the viral infections either alone or in
      combination. 3. The production results were profoundly influenced by several
      other factors, that is, breed, diet, stock density and contents of whole wheat
      grain in the food. 4. The incidence of horizontally-transmitted subclinical
      chicken anaemia virus infection in Danish broilers has decreased significantly
      during the period 1988-89 to 1992-93, probably because of improved hygiene and
      management. The incidence of adeno- and REO virus infections did not change
      during the same period. 5. It is concluded that factors other than subclinical
      viral infections presently have an economic impact on performance observed in the
      Danish broiler production.

PMID- 7583377
TI  - Interaction between dietary 1,25-dihydroxycholecalciferol and calcium and effects
      of management on the occurrence of tibial dyschondroplasia, leg abnormalities and
      performance in broiler chickens.
AB  - 1. Two experiments were performed to compare the relative effectiveness of
      feeding 1,25-dihydroxycholecalciferol (1,25-DHCC) in minimising leg abnormalities
      in broilers with other methods and to investigate interactions between dietary
      1,25-DHCC and calcium. 2. Adding 5 micrograms 1,25-DHCC/kg to a diet containing
      12 g calcium/kg was more effective than early food restriction or meal feeding in
      preventing leg abnormalities but was found to cause a growth depression. 3. The
      second experiment, which had a factorial design, with diets containing 7.5, 10.0
      and 12.5 g calcium and 0, 2.0, 3.5 and 5.0 micrograms 1,25-DHCC/kg, showed linear
      and quadratic interactions between these dietary factors. Diets with higher
      concentrations of both 1,25-DHCC and calcium resulted in growth depression
      associated with hypercalcaemia. 4. The incidence of tibial dyschondroplasia (TD)
      at 3 weeks of age was highest with the basal diet containing 7.5 g calcium/kg and
      was markedly reduced by addition of 1,25-DHCC and/or calcium. The incidence was
      very low or non-existent when 1,25-DHCC was fed at 3.5 micrograms/kg or greater.
      5. Feeding 5 micrograms/kg 1,25-DHCC had no effect on plasma 1,25-DHCC
      concentrations, although at the higher dietary calcium contents plasma
      concentrations of 25-hydroxy- and 24,25-dihydroxy-cholecalciferol were lower in
      those birds fed 1,25-DHCC. 6. It is concluded that 1,25-DHCC is most effective in
      preventing TD without accompanying growth depression when it is fed in
      conjunction with diets containing less than 10 g calcium/kg.

PMID- 7583378
TI  - Nutritive activity of soluble rice brain arabinoxylans in broiler diets.
AB  - 1. A soluble material (703 g/kg non-starch polysaccharide, 141 g/kg starch and
      166 g/kg protein) of low viscosity (termed RB-NSP), was isolated in large
      quantities from defatted Australian rice bran using a mild alkaline extraction
      and ethanol precipitation. 2. The soluble non-starch polysaccharide fraction of
      RB-NSP comprised arabinose (0.40 mol%), xylose (0.32 mol%) galactose (0.17 mol%),
      glucose (0.08 mol%) and mannose (0.03 mol%). 3. RB-NSP was included at graded
      concentrations (0, 20, 40 and 60 g/kg) in a sorghum/casein basal diet and the
      diet fed to male broilers in a classical balance trial to determine apparent
      metabolisable energy (AME). The AME values recorded were 13.26, 13.85, 14.26 and
      14.00 MJ/kg DM with a significant correlation (r = 0.65, P < 0.001) between
      dietary RB-NSP inclusion rate and dietary AME. 4. Feeding RB-NSP had no effect on
      growth, food conversion ratio or the digestibilities of starch and protein which
      were both high (0.98-0.99 and 0.88-0.89, respectively). 5. It was concluded that
      the RB-NSP may have been a substrate for hindgut fermentation in the broiler but
      that it possessed no anti-nutritive activity.

PMID- 7583379
TI  - Selection of foods by broiler chickens following corticosterone administration.
AB  - 1. The effects of corticosterone (CORT) on diet selection of broiler chickens
      offered a choice of a high protein concentrate (381 g CP/kg, 17.5 MJ/kg ME) and
      whole wheat (113 g CP/kg, 15.9 MJ/kg ME) in relation to age were examined in two
      experiments. 2. Daily intramuscular injections of 2 and 4 mg/kg of CORT for a 5-d
      period in both 2- and 5-week-old chickens resulted in increases in total food,
      protein and energy intakes. This led to a decrease in protein accretion in older
      but not younger chicks, an increase in total lipid contents of the carcase at
      both ages, and produced changes in internal organs. 3. CORT significantly reduced
      body weight gain of young but not old chickens, suggesting that mature birds
      respond better than young ones to the physiological changes caused by treatment,
      by making subsequent appropriate food choices. 4. Administration of CORT in young
      chicks increased wheat intake at 2 and 4 h after injection, while in older birds
      a similar increase was maintained up to 24 h after injection. Intake of HP food
      was decreased by both doses of CORT in young chicks but there was no significant
      effect in older chickens. 5. Changes in energy: protein ratio in the chosen diet
      appeared at 4 h after treatment in old chickens and at 24 h in younger chicks. 6.
      The results suggest that birds are able to detect metabolic changes caused by
      CORT administration and attempt to redress them by modifying their food pattern.
      The time course of the response of birds to these changes is age related.
      However, the food selection pattern did not completely compensate for the
      physiological defects.

PMID- 7583380
TI  - Use of ambroxol and bromhexine as mucolytics for enhanced diffusion of
      furaltadone into tracheobronchial secretions in broilers.
AB  - 1. Ambroxol and bromhexine were evaluated as mucolytics and to enhance the
      passage of furaltadone into tracheobronchial secretions (TBS) in chronic
      complicated respiratory disease-affected broilers. 2. Viscosity of TBS was
      noticeably increased in the ambroxol-treated birds and only slightly increased in
      the bromhexine groups; however, the physical (nature) of TBS was superior in the
      ambroxol-treated broilers. 3. There was a clear increase in the passage of
      furaltadone into tracheobronchial secretions only in the ambroxol-treated birds.
      4. Everyday use of ambroxol in broilers is discussed.

PMID- 7583382
TI  - Magnetic resonance imaging for evaluation of childhood aplastic anemia.
AB  - PURPOSE: We prospectively evaluated the ability of magnetic resonance imaging
      (MRI) of the thoraco-lumbar vertebrae to determine the relative amount of red and
      fatty marrow in children with aplastic anemia. PATIENTS AND METHODS: Twenty
      pediatric patients (ages 1-19 years) with aplastic anemia underwent T1-weighted
      (T1W, n = 31) and short T1 inversion recovery (STIR, n = 30) MRI of the midline
      sagittal thoraco-lumbar spine. Bone marrow (BM) biopsies from the posterior iliac
      crest (n = 29) were also performed. All studies were evaluated by blinded
      observers; MR grading was based on visual inspection of signal intensity. Biopsy
      estimated cellularity was compared with T1W and STIR grading when these were
      performed within 14 days of each other (n = 16). All studies were compared to a
      simultaneous absolute neutrophil count (ANC), absolute reticulocyte count (ARC),
      and platelet count. RESULTS: BM cellularity estimated by BM biopsy was
      significantly associated with STIR grading (p = 0.032, Jonckheere-Terpstra test),
      as were peripheral ANC (p = 0.044), ARC (p = 0.007), and platelet count (p =
      0.003). T1W grade was significantly associated with ANC (P = 0.011) but not ARC
      (p = 0.053) or platelet count (p = 0.377). Biopsy-estimated cellularity was
      associated with ANC (p = 0.032) and ARC (p = 0.036), but not platelet count (p =
      0.282). CONCLUSION: In childhood aplastic anemia patients, STIR (and, to a lesser
      extent, T1W) MRI of the thoraco-lumbar spine reflects BM activity, as measured by
      peripheral blood ANC, ARC, and platelet count, and BM cellularity, as measured by
      BM biopsy. MRI may thus provide a noninvasive measure of hematopoietic status.

PMID- 7583381
TI  - Abnormalities of chromosome band 11q23 and the MLL gene in pediatric
      myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an
      indicator of long survival.
AB  - PURPOSE AND METHODS: We reviewed the cytogenetic pattern of the malignant cells
      in 36 patients who were < 20 years of age and who had M4 and M5 leukemias,
      excluding M4Eo cases with inv(16). We performed fluorescence in situ
      hybridization (FISH) and molecular studies to determine the actual incidence of
      11q23/MLL abnormalities in these patients. RESULTS: Eighteen patients had 11q23
      translocations or insertions detected by cytogenetic analysis (15 cases) or by
      FISH (3 cases); 10 patients had t(9;11), all of whom had M5a. Eight patients had
      other 11q23 translocations or insertions not involving chromosome 9[t(11q23)]
      (four each had M4 or M5 leukemias). Eighteen cases with M4/M5 did not have 11q23
      abnormalities. MLL rearrangements were found in all patients with translocations
      or insertions of 11q23 who were studied. Clinically, children with t(9;11) were
      indistinguishable from other patients with M4-M5 leukemias. In contrast, the
      t(11q23) group was characterized by extreme hyperleukocytosis, CNS disease, and
      skin involvement. Patients with the t(9;11) had a better outcome when compared
      with patients in the t(11q23) group (EFS +/- SE at 3 years, 56 +/- 17% versus 10
      +/- 10%, p = 0.04), and to all the remaining children with M4-M5 leukemias (p =
      0.04). CONCLUSIONS: The combination of cytogenetic, FISH, and molecular analysis
      provides a highly sensitive strategy for detection of 11q23/MLL gene
      rearrangements in childhood M4-M5 leukemias. Our more precise classification of
      these patients allows a more accurate correlation with outcome. The favorable
      prognostic significance of the t(9;11) should be confirmed in prospective studies
      including a larger number of children as well as adults.

PMID- 7583383
TI  - Evans syndrome. Results of a pilot study utilizing a multiagent treatment
      protocol.
AB  - PURPOSE: We evaluate the efficacy of combination medical therapy in the treatment
      of ITP and AIHA episodes for patients with Evans syndrome. PATIENTS AND METHODS:
      Five patients with Evans syndrome were followed for a median of 3.8 years and
      were treated according to our multiagent (IVIG, steroids, vinca alkaloids,
      androgens, and cyclosporin) protocol. RESULTS: All patients initially received
      IVIG and IV steroids for either acute hemolysis or thrombocytopenia. IV vinca
      alkaloids and oral Danazol were added in three patients for ITP. All responded,
      but two required frequently repeated vinca alkaloid treatments. Both patients
      treated with vinca alkaloids for severe hemolysis responded. Two patients
      received oral cyclosporin for refractory ITP; one had a transient response.
      Splenectomy was not included in our regimen. Two patients underwent splenectomy
      prior to their referral; both required further therapy. In addition, review of
      the clinical courses of our patients indicate that the DAT may be a prognostic
      factor for the chronicity of ITP. CONCLUSION: In view of the high relapse rates
      after splenectomy and the encouraging results of our pilot study, we suggest that
      medical treatment with combination agents (IVIG, steroids, vinca alkaloids,
      androgens and possibly cyclosporin) may provide a useful therapeutic approach to
      patients with Evans syndrome.

PMID- 7583384
TI  - A novel hereditary macrothrombocytopenia.
AB  - PURPOSE: A family is described in which macrothrombocytopenia and hearing loss
      are transmitted in an autosomal-dominant fashion. PATIENTS AND METHODS: Several
      members of the family were studied extensively. Review of blood smears,
      coagulation studies, platelet function testing, and electron microscopy were
      performed. Platelet membrane glycoproteins were examined using flourescein
      conjugated antibodies and flow cytometry. RESULTS: Platelet counts ranged from
      50,000 to 123,000/microliters. Both mean platelet diameter and volume were
      increased. No leukocyte inclusions were noted by light or electron microscopy.
      Platelet aggregation was normal with adenosine diphosphate (ADP), collagen, and
      ristocetin but diminished with epinephrine and arachidonic acid. Flow cytometry
      showed normal platelet membrane glycoproteins and the unusual expression of
      glycophorin A on 40-60% of the giant platelets. CONCLUSIONS: This family's
      syndrome of macrothrombocytopenia and late-onset hearing loss appears to
      represent a novel giant platelet disorder. The expression of glycophorin A
      suggests disordered megakaryocytopoiesis with the early release of immature
      platelets.

PMID- 7583385
TI  - Refractoriness to platelet transfusions in children with acute leukemia.
AB  - PURPOSE: We evaluated the incidence of clinically significant refractoriness to
      platelet transfusions in children with acute leukemia. PATIENTS AND METHODS: We
      reviewed the complete transfusion records up to July 1993 of all 213 patients
      diagnosed with acute leukemia at our institution over the 4-year period 1987 to
      1990. The transfusion protocol called for all patients requiring transfusion of
      red cell and/or platelet concentrates to initially receive components that were
      not leukocyte reduced. Patients suspected clinically to be refractory to
      platelets were tested for anti-human leukocyte antigen (HLA) antibodies and those
      that tested positive were switched to HLA-matched platelets. RESULTS: Of 184
      patients diagnosed with acute lymphoblastic leukemia (ALL), 133 (72%) required
      platelet support, whereas all 29 patients with acute myeloid leukemia (AML) were
      transfused with platelets. The incidence of clinically suspected refractoriness
      to non-leukocyte-reduced platelets, which was confirmed by a positive test for
      anti-HLA antibodies and which resulted in a switch to HLA-matched platelets, was
      nine of 29 (31%) for patients with AML but only three of 133 (2.3%) for patients
      with ALL. CONCLUSIONS: The results of this study indicate that clinically
      significant platelet refractoriness requiring transfusion of HLA-matched
      platelets occurs infrequently in childhood ALL. For this group of patients, use
      of leukocyte-depleted cellular components for the purpose of preventing platelet
      refractoriness cannot be justified. This approach may be appropriate for children
      with AML.

PMID- 7583386
TI  - Differentiating effects of 1,25-dihydroxycholecalciferol (D3) on LA-N-5 human
      neuroblastoma cells and its synergy with retinoic acid.
AB  - PURPOSE: 1,25-Dihydroxycholecalciferol (D3) plays an important role in embryonic
      development and cell differentiation. It has previously been reported to decrease
      c-myc expression by HL-60 cells and downregulate c-myc expression by breast and
      ovarian cancer cells. We report the results of our investigations into the
      differentiating effects of D3 on LA-N-5 human neuroblastoma cells. METHODS: LA-N
      5 human neuroblastoma cell line was treated with D3, retinoic acid (RA), D3 and
      RA, or solvent control. Growth inhibitory effects, neurite extension,
      acetylcholinesterase activity, invasiveness, motility, and N-myc protein
      expression were examined following treatment. RESULTS: Growth inhibition was
      observed at concentrations of > 24 nM. D3 stimulated the differentiation of LA-N
      5 cells as demonstrated by increased neurite outgrowth, increased
      acetylcholinesterase activity, and decreased invasiveness. A decrease in N-myc
      expression was observed in immunostained cells treated with either agent alone,
      with a more profound effect appreciated with the combination. CONCLUSION: Vitamin
      D3 decreases N-myc expression in LA-N-5 human neuroblastoma cells, with extended
      treatment causing growth inhibition and differentiation. When used in combination
      with RA, these effects are more profound than with either agent alone. The
      therapeutic use of differentiating agent combinations such as D3 and RA may
      provide a relatively nontoxic means of treating susceptible tumor types.

PMID- 7583387
TI  - Pediatric germ cell tumor. An experience with BEP.
AB  - PURPOSE: This study is an analysis of our experience with bleomycin, etoposide,
      and cisplatin (BEP) chemotherapy, in pediatric germ cell tumors (GCTs). PATIENTS
      AND METHODS: The study included all children (age < 16 years) who were registered
      between May 1988 and May 1993 with a histologically confirmed diagnosis of GCT
      and received BEP chemotherapy. In addition to the clinicopathological features,
      the response rate, survival rate, and toxicity were analyzed. RESULTS: There was
      a total of 56 patients, of whom 22 had an ovarian tumor and 17 each had a
      testicular or an extragonadal tumor. Histologically, endodermal sinus tumor was
      the most common type (62%). Tumor markers were increased in 89% (50 of 56).
      Complete responses were observed in 89.1% (49 of 55) and partial responses in
      10.9% (6 of 55) of the evaluable patients. Five-year actuarial survival was 83%
      and progression free survival was 93%. Median follow-up was 18 months. Median
      survival is not yet reached. The chemotherapy was well tolerated. CONCLUSIONS:
      From the present report, it is apparent that BEP chemotherapy is very effective
      and well tolerated in children with GCT. The data probably suggests that
      conservative surgery, when combined with effective chemotherapy, can result in
      cure of the majority of children with GCTs.

PMID- 7583389
TI  - Cyclophosphamide dose escalation in combination with vincristine and actinomycin
      D (VAC) in gross residual sarcoma. A pilot study without hematopoietic growth
      factor support evaluating toxicity and response.
AB  - PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) initiated an escalating-dose
      cyclophosphamide (Cyc) pilot without hematopoietic growth factor (HGF) support in
      combination with vincristine (Vcr) and actinomycin-D (Amd), known as VAC, to
      establish a Cyc dose with myelotoxicity comparable to an ifosfamide (Ifos), Vcr,
      and Amd combination regimen (VAI). A Cyc dose equivalent to Ifos was to be
      determined when comparable myelotoxicity was achieved. PATIENTS AND METHODS:
      Patients with either rhabdomyosarcoma or undifferentiated soft-tissue sarcoma and
      gross residual (clinical group III) disease were eligible for the VAC pilot.
      Feasibility and toxicity were evaluated in the VAC pilot at each Cyc level before
      escalating the dose. Starting at CYC 1.2 g/m2 dose escalation was planned at
      increments of 20-25% in cohorts of 8-10 patients until myelotoxicity at a severe
      or worse grade was seen in > 90% of the patients. RESULTS: One hundred nineteen
      eligible patients were evaluated for toxicity and response at four Cyc levels:
      1.2, 1.5, 1.8, and 2.2 g/m2. Eight of 87 (9%) evaluable at 2.2 g/m2 had a toxic
      death. Six of these were attributable to myelotoxicity. Patients age 1-3 years
      were most vulnerable. The overall complete response (CR) rate of 68% was poorly
      predicted by the weeks 8 and 20 CR rates of 20 and 40%, respectively. During the
      first year and overall, myelotoxicity at 2.2 g/m2'1 with VAC was comparable to
      Ifos 1.8 g/m2'5. Cyc was relatively more myelotoxic than Ifos in the second year
      of the VAC pilot. Based on actual amount of drug given, a standardized Ifos dose
      of 9.0 g/m2 was equivalent to 2.1 g/m2 of Cyc, giving an Ifos/Cyc ratio of 4.3.
      CONCLUSION: Myelotoxicity using 2.2 g Cyc/m2 in a single intravenous infusion was
      dose limiting in this VAC pilot without HGF. In the first year and overall,
      myelotoxicity is comparable to that with VAI using Ifos at 9.0 g/m2. An ongoing
      IRS-IV randomized trial of VAC and VAI should provide a comparison of the
      efficacy of Ifos and Cyc in children and adolescents with embryonal or alveolar
      rhabdomyosarcoma and undifferentiated soft-tissue sarcomas.

PMID- 7583390
TI  - Vesiculated erythrocytes as a determination of splenic reticuloendothelial
      function in pediatric patients with Hodgkin's disease.
AB  - PURPOSE: To determine the effect of low-dose total, or subtotal, nodal
      irradiation (TNI/sub-TNI) on splenic reticuloendothelial function in pediatric
      patients with Hodgkin's Disease (HD). PATIENTS AND METHODS: Pediatric and
      adolescent patients with advanced stage HD were accrued from two Pediatric
      Oncology Group studies and subdivided into three groups: the first had
      chemotherapy (CT) only; the second received chemotherapy and low-dose (2,100 cGy)
      TNI or subtotal TNI (sub-TNI); the third underwent staging laparotomy with
      splenectomy followed by CT, with or without low-dose radiotherapy. Vesiculated
      erythrocyte counts (VRBC) were performed on all patients using Nomarski
      interference phase optics at the conclusion of therapy. RESULTS: The mean VRBCs
      were 3.2%, and 3.8% for the non-splenectomized patients who received chemotherapy
      only, and chemotherapy plus low-dose splenic irradiation, respectively. For those
      who underwent splenectomy before chemotherapy, the VRBC was 36.7%. Statistical
      analysis revealed no difference in vesiculated erythrocyte percentages between
      the CT only group and the CT + TNI/sub-TNI patients; however, there was a
      significant difference between both of these groups and the splenectomized
      patients. CONCLUSIONS: Our results indicate that the addition of low-dose splenic
      irradiation to chemotherapy in children and adolescents with advanced-stage
      Hodgkin's disease does not adversely affect splenic reticuloendothial function.

PMID- 7583388
TI  - Cessation of antibiotics regardless of ANC is safe in children with febrile
      neutropenia. A preliminary prospective trial.
AB  - PURPOSE: This study was designed to evaluate the safety and efficacy of stopping
      antibiotic treatment regardless of absolute neutrophil count (ANC) or signs of
      impending neutrophil recovery in children with febrile neutropenia (FN) and no
      identifiable infectious source. PATIENTS AND METHODS: Thirty-two consecutive
      cases of FN without identifiable source were prospectively evaluated. Patients
      were examined, cultured, and initially treated with ceftazidime +/- vancomycin.
      Antibiotics were discontinued and patients discharged regardless of ANC
      (WBC/microliter x [% segs + bands]) once all the following criteria were met:
      afebrile > or = 24 h; cultures negative at 48 h; thermometer and telephone
      available at home. Prompt notification of fever (T > 38.3 degrees C) and
      readmission were required. RESULTS: Median ANC was 60/microliters on admission
      and 160/microliters at discharge. Median length of treatment was 3 days. Four
      patients were readmitted for FN, and two patients were readmitted afebrile for
      cultures which became positive after discharge. None of the 32 cases suffered
      apparent complications from early discharge. CONCLUSION: Results of this
      preliminary trial suggest that cessation of antibiotics regardless of ANC is safe
      in cases of FN without identifiable source, provided that marrow is not
      infiltrated and that recurrent fever receives prompt antibiotic retreatment.

PMID- 7583391
TI  - Long-term central venous access in patients with sickle cell disease. Incidence
      of thrombotic and infectious complications.
AB  - PURPOSE: Central venous access devices (CVAD) have been used with increasing
      frequency in recent years among pediatric patients. We retrospectively reviewed
      our experience in 25 children and young adults with sickle cell disease (SCD)
      over a 4 1/2 year period in an attempt to define occurrence rates of
      perioperative complications, thrombosis requiring catheter removal, and
      infectious episodes. PATIENTS AND METHODS: The setting was a university
      associated tertiary children's hospital. Patients were 25 children and young
      adults (ages 8 months to 23 years) with SCD who required CVAD placement between
      February 1987 and April 1992. A total of 31 catheters (totally implantable ports
      and partially implanted catheters) were placed for 17,444 patient catheter days.
      RESULTS: Rates of significant perioperative complications, thrombotic events
      requiring catheter removal, and infectious episodes were recorded. No
      perioperative complications were noted. Five episodes of catheter occlusion
      requiring replacement occurred in two patients (0.29 per 1,000 catheter patient
      days, involving 8% of patients and 16% of catheters). Fifteen episodes of
      catheter-associated bacteremia occurred in eight patients (0.86 per 1,000
      catheter patient days involving 32% of patients and 26% of catheters). Three
      catheters required removal because of infection unresponsive to antibiotic
      therapy. CONCLUSION: The occurrence of thrombosis requiring catheter removal and
      infection in our population of patients with SCD was comparable to that reported
      in patients with malignant disease, cystic fibrosis and acquired immune
      deficiency syndrome. CVAD represents an effective, reliable, and reasonably safe
      means of establishing and maintaining venous access for a selective group of
      children and young adults with SCD who have limited peripheral venous access and
      require intravenous therapies.

PMID- 7583392
TI  - Boys but not girls with T-lineage acute lymphocytic leukemia (ALL) are different
      from children with B-progenitor ALL. Population-based data results of initial
      prognostic factors and long-term event-free survival. Swiss Pediatric Oncology
      Group.
AB  - PURPOSE: In a population-based data registry of children with ALL, initial
      prognostic factors were analyzed with regard to long-term event-free survival.
      PATIENTS AND METHODS: From 1976-1991 the Swiss Pediatric Oncology Group (SPOG)
      observed 610 children and adolescents who were diagnosed with ALL before the age
      of 15 years, and who were prospectively treated according to different study
      protocols. Immunophenotyping of B-progenitor- or T-lineage ALL was possible in
      573 children. Leucocyte count, age, and sex were compared with regard to
      immunophenotype of lymphoid cells and to event-free survival on Kaplan Meier
      curves by statistical analyses including multivariate analysis and the Cox
      regression backward elimination test. RESULTS: Of the 573 patients who were
      immunophenotyped 86.4% had B-progenitor ALL and 13.6% T-lineage ALL. The
      differences between B-progenitor ALL and T-lineage ALL with respect to initial
      white blood cell count, age and gender were significant. A comparison of event
      free survival in children with B-progenitor ALL versus T-lineage ALL revealed
      significant differences in boys (p < 0.001) but not in girls (p = 0.183).
      Statistical tests showed gender to be an independent risk factor. CONCLUSION: The
      long-term outcome following identical treatment of both genders was significantly
      better in girls with T-lineage ALL than in boys. Girls with T-lineage ALL, but
      not boys with T-lineage ALL, had a prognostic outcome similar to children with B
      progenitor ALL.

PMID- 7583393
TI  - Bone marrow transplantation for infantile malignant osteopetrosis.
AB  - PURPOSE: Most patients diagnosed with malignant osteopetrosis die during infancy
      or early childhood from hemorrhage and infection due to bone marrow failure.
      Allogeneic bone marrow transplantation (BMT) has been reported to provide
      curative therapy for this disorder. We report our experience with eight patients
      with malignant osteopetrosis who underwent BMT. PATIENTS AND METHODS: Between May
      1987 and August 1992, eight children with malignant osteopetrosis underwent
      allogeneic BMT. Median age at BMT was 9 months (range, 2-36 months). Six patients
      received marrow from HLA-identical sibling donors, one from phenotypically
      matched father, and one from a one antigen mismatched father. BMT conditioning
      for all patients was busulfan 16 mg/kg and cyclophosphamide 200 mg/kg each
      administered over 4 days. Graft versus host disease (GVHD) prophylaxis included
      cyclosporin A in six patients or cyclosporin A and methotrexate in two patients.
      RESULTS: Six patients, including those who received bone marrow from their
      father's, engrafted as documented by bone marrow biopsy showing an increase in
      osteoclasts in all cases and by chromosomal analysis in four patients. Two
      patients died without engraftment. Three out of six patients engrafted are alive
      and well at the follow-up of 48, 63, and 81 months. Serum calcium, alkaline, and
      acid phosphatase levels normalized within 2 months. These patients have full bone
      marrow reconstitution. Serial radiologic studies revealed bone marrow remodelling
      and a new nonsclerotic bone formation. Vision improved dramatically in the
      youngest patient. CONCLUSION: BMT offers cure to patients with malignant
      osteopetrosis with reconstitution of bone marrow and correction of metabolic
      disturbances. In our experience, reversibility in neurosensory deficit is
      possible when BMT is done at an early age.

PMID- 7583394
TI  - The role of the uniform.

PMID- 7583395
TI  - The creation of an N.D.U.--the Bradford story.

PMID- 7583396
TI  - Asthma: support in the community.

PMID- 7583397
TI  - Enuresis.

PMID- 7583399
TI  - A pond full of water lilies.

PMID- 7583398
TI  - Tailor-made courses in community children's nursing in order to qualify as a
      specialist practitioner.

PMID- 7583400
TI  - The pathways to a specialism.

PMID- 7583401
TI  - Community: the student perspective.

PMID- 7583402
TI  - Managing multiple births. Part 2: Conception and beyond.

PMID- 7583404
TI  - Devolving supervision.

PMID- 7583405
TI  - Small group practices. Part 1: The manager's perspective.

PMID- 7583406
TI  - The hurdles of direct entry.

PMID- 7583407
TI  - Perinatal death: the lessons from CESDI.

PMID- 7583403
TI  - Hidden misery of hydatidiform mole.

PMID- 7583408
TI  - Stress at work.

PMID- 7583409
TI  - Questionnaire training for breastfeeding.

PMID- 7583410
TI  - Women in normal labour.

PMID- 7583412
TI  - Midwives must determine midwifery matters.

PMID- 7583413
TI  - A different perspective.

PMID- 7583415
TI  - Good preconception care starts in school.

PMID- 7583414
TI  - Managing multiple births. Part 3: Supporting parents.

PMID- 7583416
TI  - Home births: the midwife's dilemma.

PMID- 7583411
TI  - We do need a new Midwives' Act!

PMID- 7583417
TI  - Small group practices. Part 2: The midwife's perspective.

PMID- 7583418
TI  - Rhesus sensitisation.

PMID- 7583419
TI  - Midwifery literature: getting started.

PMID- 7583422
TI  - Between a rock and a hard place.

PMID- 7583420
TI  - Breastfeeding: promoting good practice.

PMID- 7583423
TI  - Higher education: do we know what we want?

PMID- 7583421
TI  - What if the midwife falls down the stairs?

PMID- 7583424
TI  - Food for thought: a menu for supervision.

PMID- 7583426
TI  - Nurses' sensitivity to the ethical aspects of clinical practice.
AB  - The purpose of this study was to describe the extent to which nurses perceive the
      ethical dimensions of clinical practice situations involving patients, families
      and health care professionals. Using the composite theory of basic moral
      principles and the professional standard of care established by legal custom as a
      framework, situations involving ethical dilemmas were gleaned from the nursing
      literature. They were reviewed for content validity, clarity and
      representativeness in a two-stage process by expert panels. The situations were
      presented in a written format to a convenience sample of nurses (n = 125), who
      were primarily staff nurses (65.6%). Respondents' judgements about whether the
      main issue of each situation concerned ethics ranged from a low of 0.8% to a high
      of 40%. From analyses of the categories into which the majority of subjects
      placed each situation, it was concluded that these nurses generally perceived
      ethics as the main issue in situations that directly involve patients' autonomy.
      Analysis yielded unanticipated findings about the themes in ethical situations to
      which nurses in practice may respond.

PMID- 7583425
TI  - Artificial personhood: nursing ethics in a medical world.
AB  - Artificial persons are those who speak and act for others. Nurses speak and act
      for patients as well as for physicians and institutions, or, more aptly,
      institutionalized medicine. Yet, acting for institutionalized medicine can be
      harmful to nurses, due to the psychological experience of moral distress and the
      loss of integrity of their practice. This paper illustrates the harm to nurses as
      expressed in narratives of their practice, and suggests some initial steps we
      might take in resisting the artificial personhood imposed by institutionalized
      medicine.

PMID- 7583427
TI  - Culture and ethics: a tool for analysing the effects of biases on the nurse
      patient relationship.
AB  - For most nurses world-wide, activities are centred around working directly with
      patients and so the nurse-patient relationship is of the greatest importance.
      Ethnocentrism on the part of the health care community has led to misdiagnosis,
      mistreatment and undertreatment of culturally diverse individuals world-wide.
      This author discusses a tool, Greipp's Model of Ethical Decision-Making, which
      can be used to assist nurses in analysing the effects of culture, beliefs and
      diversity upon the caregiver and care recipient within an ethical framework.

PMID- 7583428
TI  - Ethical issues in qualitative nursing research.
AB  - This article is concerned with ethical issues that have to be considered when
      undertaking qualitative research. Some of the issues--such as informed consent,
      the dignity and privacy of the research subjects, voluntary participation and
      protection from harm--are the same as in other types of research and have their
      basis in moral and ethical principles. Qualitative research, however, generates
      specific ethical problems because of the close relationship that researchers form
      with participants. Qualitative research with patients is especially difficult
      because of their vulnerability and lack of power in the clinical situation.
      Therefore the potential conflict between the dual role of the nurse--the
      professional and the research roles--has to be solved. Researchers also learn how
      to cope with the tension of subjective and objective elements of the research.
      Nurses who attempt qualitative research have to consider a variety of complex
      ethical issues, which are addressed in this paper.

PMID- 7583431
TI  - Code of professional conduct. The College of Radiographers.

PMID- 7583429
TI  - Gender differences in moral reasoning among physicians, registered nurses and
      enrolled nurses engaged in geriatric and surgical care.
AB  - Physicians, registered nurses (RNs) and enrolled nurses (ENs) engaged in
      geriatric (n = 49) and surgical (n = 59) care at a large hospital in Sweden gave
      180 accounts of morally difficult care episodes. In total, the ENs (n = 40) gave
      78, the RNs (n = 38) 55 and the physicians (n = 30) 47 accounts; there were 83
      from geriatric care and 97 from surgical care. Forty-nine participants were male,
      and 59 were female; there were no differences in gender in the form and content
      of the moral reasoning disclosed in either morally difficult care episodes or in
      the complete interviews when coded as mainly narrative or propositional, or as
      showing a care or a justice orientation. The ENs showed a care orientation, while
      RNs and physicians, to an equal degree, showed both a justice and a care
      orientation. The ENs also used narrative reasoning more often than RNs and
      physicians. No differences were seen between the two health care specialties.

PMID- 7583432
TI  - Can nursing survive? A view through the keyhole.

PMID- 7583430
TI  - Midwives, their employers and the UKCC: an eternally unethical triangle.
AB  - The majority of midwives in the UK are employed within the NHS. They are legally
      bound to fulfil their contractual obligations to their employers. At the same
      time they are professionally mandated to interpret and act on the UKCC's Code of
      professional conduct. Midwives have always maintained that they are autonomous
      practitioners, and the Code is written in a way that endorses this belief.
      Underlying the Code is the assumption that midwives have moral and professional
      freedom to act on its imperatives. However, midwives' claim to autonomy is
      flawed, and therefore the Code's claim to be a source of empowerment is also
      flawed. Underlying the difficulties is a conflict derived from the imposition of
      a deontologically-based professional Code on to a workforce that is constrained
      within and employed by the utilitarian-based NHS.

PMID- 7583433
TI  - Your journal's methods of quality assurance through the process of refereeing.

PMID- 7583434
TI  - Superantigen toxic shock syndrome toxin-1 (TSST-1) enhances the replication of
      HIV-1 in peripheral blood mononuclear cells through selective activation of CD4+
      T lymphocytes.
AB  - Staphylococcus aureus has been recognized as a common cause of bacteremia of such
      infections in human immunodeficiency virus type 1 (HIV-1)-seropositive patients.
      Some staphylococcal exotoxins are recognized as superantigens. We have found that
      superantigen toxic shock syndrome toxin-1 (TSST-1) brings about a high level of
      viral production in HIV-1-infected peripheral blood mononuclear cells (PBMCs)
      through their activation in vitro. The p24 antigen level in the culture
      supernatant markedly increased in the presence of TSST-1 at a concentration of 1
      pg/ml or higher. Fluorescent-activated cell sorter analysis revealed that TSST-1
      specifically activated CD4+ T lymphocytes. Although significant production of
      tumor necrosis factor alpha (TNF-alpha) was observed in uninfected PBMCs treated
      with TSST-1 after 96 h of incubation, much earlier (after 12 h of incubation)
      production of TNF-alpha was identified in HIV-1 infected PBMCs with or without
      TSST-1 treatment. The addition of anti-TNF-alpha antibody to the culture medium
      resulted in a dramatic decrease in HIV-1 replication. These results suggest that
      the enhanced replication of HIV-1 by TSST-1 in PBMCs is attributable mainly to
      the activation of CD4+ T lymphocytes and that the induction of TNF-alpha further
      enhances replication. Since the enhancement of HIV-1 replication by TSST-1 occurs
      in a concentration range of picograms per milliliter, the superantigen TSST-1 may
      play an important role in the pathogenesis and clinical course of HIV-1
      infections.

PMID- 7583435
TI  - Neutralizing antibodies in slowly progressing HIV-1 infection.
AB  - Ten asymptomatic individuals who had experienced only limited CD4+ cell loss
      after prolonged infection with HIV-1 were studied. These individuals had a mean
      CD4+ cell count of 674 x 10(6) cells/L and a mean duration of infection of 8.5
      years. Also included were 10 asymptomatic HIV-1-infected individuals who, over a
      similar period of infection (7.5 years), had experienced a profound loss of CD4+
      cells (mean CD4+ cell count, 54 x 10(6) cells/L). Proviral load was determined
      using a semiquantitative polymerase chain reaction and was significantly lower in
      the subjects with slowly progressing infection (SPI) than in subjects with
      rapidly progressing infection (RPI) (4,000 vs. 40,000 proviral copies/10(6)
      peripheral blood mononuclear cells; p = 0.0089). Isolation of virus was attempted
      in all individuals but succeeded only in 6 of 10 individuals with SPI versus all
      10 individuals with RPI. Four of six virus isolates obtained from individuals
      with SPI and 6 of 10 obtained from individuals with RPI were of the syncytia
      inducing phenotype. We determined the neutralizing activity of serum against
      HIVMN, HIVIIIB, and the contemporaneous autologous isolate when available. Serum
      from individuals with SPI generally neutralized the contemporaneous isolate,
      whereas serum from individuals with RPI did not [geometric mean antibody titer
      (GMT), 45 vs. 3; p = 0.0047]. There was no difference in neutralizing ability
      against HIVMN (GMT,2,593 vs. 2,263; p = 0.74) and only a small difference against
      HIVIIIB (GMT, 115 vs. 50; p = 0.075). Our results indicate that individuals with
      SPI are characterized by an ability to neutralize their own HIV strain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7583437
TI  - Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific cytotoxic T
      lymphocytes by pentoxifylline.
AB  - HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the
      host immune response against HIV infection, and these cells release a variety of
      cytokines when they meet their target antigen. Since the phosphodiesterase
      inhibitor pentoxifylline is being used as a therapeutic agent in clinical trials
      of HIV infection due to its inhibitory effect on virus replication in vitro, we
      examined the effect of pentoxifylline on cytotoxicity and cytokine secretion by
      HIV-specific CD8+ CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and
      suppressed interferon-gamma, tumor necrosis factor-alpha, and granulocyte
      macrophage colony-stimulating factor release by these cells at the transcription
      level. Suppression of cytokine release resulted in reduced capacity of the CTLs
      to induce HLA class I and ICAM-1 expression and to stimulate HIV-1 replication.
      These results suggest that inhibition of HIV-specific CD8+ CTLs by pentoxifylline
      may be therapeutically relevant. Moreover, this study extends previous
      observations by demonstrating that, in addition to its ability to suppress
      cytokine production by macrophages and CD4+ T helper cells, pentoxifylline may
      inhibit cytotoxicity and cytokine secretion by antigen-specific CD8+ cytotoxic T
      lymphocytes.

PMID- 7583438
TI  - Quantifying HIV-1 RNA using the polymerase chain reaction on cerebrospinal fluid
      and serum of seropositive individuals with and without neurologic abnormalities.
AB  - We quantified HIV-1 RNA levels (copies per milliliter) in cerebrospinal fluid
      (CSF) and serum from subjects at various stages of HIV-1 disease and determined
      the relationship of RNA levels to clinical and neurologic disease status (HND)
      and to laboratory values. Ninety-seven HIV-1-seropositive men without CNS
      opportunistic infections, tumors, or neurosyphilis and 13 high-risk seronegative
      controls were included in the study. Each individual underwent a structured
      interview and physical and neurologic examinations, followed by standardized
      collection of blood and CSF. A custom-designed, fully automated polymerase chain
      reaction (PCR) system was used to perform a minimum of four separate
      amplifications per specimen, using two HIV-1 gag primer pairs. Southern blotting
      followed by hybridization with product-specific probes was used for post-PCR
      detection. The number of copies per milliliter was determined by relating
      unknowns to a built-in dilution-series standard curve using an image analysis
      system. HIV-1 RNA was detectable in 96% of the sera, 78% of the concentrated CSF
      samples, and 54% of the unconcentrated CSF samples. Serum RNA levels were
      significantly higher than in CSF. Serum RNA levels were significantly inversely
      correlated with CD4+ cell counts (p = -0.34; p = 0.03): i.e., higher RNA levels
      in seropositive subjects were associated with lower numbers of CD4+ cells. Serum
      RNA levels correlated positively with number of AIDS-related symptoms,
      dysfunction scores for total neurological examination, mental status score,
      cranial nerve score, and CNS motor signs score. Serum RNA levels did not
      correlate significantly with length of time on zidovudine therapy, intrathecal
      IgG synthesis rate, or albumin leakage. RNA levels in CSF significantly
      correlated only with intrathecal IgG synthesis rate and with serum RNA levels.
      These results confirm that serum levels of HIV-1 RNA correlate with HND and
      inversely correlate with CD4 counts, demonstrating that HND occurs predominantly
      in late stages of HIV-1 disease, although HIV-1 RNA can be detected in CSF from a
      majority of HIV-1-seropositive individuals at all stages of disease, which
      suggests that there can be early penetration of HIV into the CNS. However, HND
      can occur in the absence of high levels of CSF HIV-1 RNA. We also found that the
      concentration of HIV-1 in CSF is correlated with intrathecal IgG synthesis rate.

PMID- 7583436
TI  - Effect of antibody to HIV-1 Tat protein on viral replication in vitro and
      progression of HIV-1 disease in vivo.
AB  - In HIV-1-infected cell cultures, a relatively low concentration (5 micrograms/ml)
      of monoclonal antibody (mAb) against HIV-1-transactivating Tat protein was an
      efficient inhibitor of HIV-1 replication both in HIV-1(IIIB)-infected Jurkat cell
      and peripheral blood mononuclear cell (PBMC) cultures and significantly reduced
      the expression of a Tat-responsive CAT-reporter construct in HIV-1(IIIB)-infected
      Jurkat cells. Anti-Tat mAb also caused a significant reduction and a consistent
      delay in HIV-1 replication when added to PBMCs from HIV-1-infected patients
      cocultivated with phytohemagglutinin (PHA)-stimulated normal PBMCs. These data
      indicate that an autocrine-paracrine loop sustained by extracellular Tat protein,
      which is actively released by HIV-1-infected cells, may affect HIV-1 replication
      in cell cultures in vitro. An inverse relationship between natural anti-Tat
      antibody levels and p24 antigenemia was demonstrated by retrospective analysis of
      serial serum samples obtained from 10 HIV-1-seropositive hemophiliac patients
      followed over a 7-9-year period. This datum points to a possible influence of
      anti-Tat antibody on the progression of HIV-1 disease in vivo. These findings
      have strong implications for Tat protein as a possible target for specific
      immunotherapy in HIV-1-infected patients.

PMID- 7583440
TI  - Zygomycosis (mucormycosis) and HIV infection: report of three cases and review.
AB  - We report three cases of zygomycosis (mucormycosis) occurring in three
      individuals infected with the human immunodeficiency virus (HIV) and review 12
      other published cases. We present the only two case reports of disseminated
      zygomycosis in AIDS patients, and the only AIDS patient with renal zygomycosis to
      survive without nephrectomy, receiving intravenous (i.v.) amphotericin alone.
      Coinfection with zygomycosis and HIV is rare, occurs primarily in patients with
      low CD4+ lymphocyte counts, does not always require the usual predisposing
      conditions for zygomycosis, and may be the presenting opportunistic infection
      among HIV-infected persons. Transient episodes of neutropenia occurring within 4
      months before presentation may be a risk factor for this disease. Zygomycosis may
      arise in multiple sites including the basal ganglia, cutaneous tissue, kidney,
      respiratory tract, and may be disseminated. Occurring more commonly in, but not
      restricted to, injection drug users, it is significantly associated with sites
      other than basal ganglia in those patients with advanced HIV disease or AIDS. The
      presenting symptoms are related to the site of involvement, and the illness may
      develop insidiously or progress rapidly to a fulminant course. Successful therapy
      usually consists of surgical debridement and intravenous amphotericin B. Overall
      mortality in this review is 40%, and is significantly associated with sites of
      disease inaccessible to surgical debridement.

PMID- 7583439
TI  - PCR analysis of HIV-seronegative, heterosexual partners of HIV-infected
      individuals.
AB  - A cohort of human immunodeficiency virus (HIV)-discordant couples was established
      to evaluate risk factors associated with heterosexual viral transmission.
      Polymerase chain reaction (PCR) was utilized to document the HIV-uninfected
      status among members of discordant heterosexual couples and to rule out
      immunosilent infection. HIV DNA PCR specific for a gag gene region was performed
      on peripheral blood mononuclear cell samples from 203 HIV antibody-negative
      adults who have long-term heterosexual relationships with HIV-infected partners.
      The results were negative for 200 but consistently positive in three individuals.
      More extensive evaluation of these three individuals with an additional primer
      pair specific for the envelope gene, quantitative DNA PCR, multiple additional
      time points, and variable nucleotide tandem repeat analyses revealed specimen
      processing problems in two cases but an apparent true positive PCR assay in the
      third case. This subject remains antibody and PCR negative for a 32-month follow
      up period. These results confirm previous studies that document a negligible
      incidence of occult HIV infection as delineated by PCR in antibody negative
      heterosexual partners of HIV-infected individuals. Specimen processing errors
      occur at a low rate (1% in this study) and require careful evaluation. The
      possibility of transient, aborted infection versus successful infection with a
      long immunosilent period was observed in a single individual. Definitive
      resolution of infection status will require long-term evaluation.

PMID- 7583441
TI  - The 90K tumor-associated antigen and clinical progression in human
      immunodeficiency virus infection.
AB  - We investigated the possibility that a secreted glycoprotein of approximately
      90,000 daltons, termed 90K and identified as a member of the protein superfamily
      characterized by the scavenger receptor cysteine-rich (SRCR) domain, might have
      value as a predictor of progression to acquired immunodeficiency syndrome (AIDS)
      in subjects infected with the human immunodeficiency virus (HIV). Among 488 HIV
      seropositive intravenous drug users with a median follow-up of 32.5 months, high
      levels of serum 90K at baseline proved to be a significant predictor of faster
      progression to AIDS, either as a continuous variable (log 90K; p < 0.0001) or as
      a dichotomous variable with an optimized cutoff point of 30 U/ml (p < 0.00001).
      Analysis of 90K in relation to known prognostic factors found an association with
      CD4 count, beta 2-microglobulin, and p24 antigen but none with neopterin. In
      multivariate analysis, the baseline 90K level was an independent predictor of
      AIDS. As compared with subjects with low levels of 90K, the relative risk of
      developing AIDS was 3.5 (95% CI 1.9-6.5) among those with high levels of 90K. The
      predictive value of 90K was maintained after stratification by baseline CD4
      count: among subjects with > or = 500 x 10(6)/L CD4 cells, the proportion in whom
      AIDS developed was 10.5% for those with 90K levels < or = 30 U/ml as compared
      with 20% for those with 90K above the cutoff point (p = 0.006). Serum 90K is an
      independent predictor of the risk for progression to AIDS in HIV-infected
      subjects, including those whose CD4 counts have not fallen.

PMID- 7583443
TI  - CD4+ and CD8+ lymphocytes of patients with AIDS synthesize increased amounts of
      interferon-gamma.
AB  - Individual cells capable of interferon-gamma (IFN-gamma) synthesis are easily
      detected by immunofluorescence and flow cytometric analysis using an anti-IFN
      gamma monoclonal antibody as specific reagent. By IFN-gamma flow cytometry assay,
      we demonstrated that HIV-seropositive patients, starting at the early stage of
      viral infection, generally have an increased percentage of lymphocytes
      potentially able to produce IFN-gamma, compared with healthy blood donors. IFN
      gamma expression in patient lymphocytes was observed to increase with the
      progressive stages of HIV infection, with the highest figures occurring in stage
      C patients. Such increased IFN-gamma expression involved both CD4+ and CD8+ T
      cell subsets. Most interestingly, we found patients at the same stage of HIV
      infection who had similar numbers of total and CD4+ lymphocytes but highly
      different percentages of lymphocytes potentially capable of producing IFN-gamma.

PMID- 7583442
TI  - Comparison of the declines in CD4 counts in HIV-1-seropositive female sex workers
      and women from the general population in Nairobi, Kenya.
AB  - Studies from Kenya have reported rapid clinical disease progression among HIV
      infected professional sex workers. The reasons for this rapid decline are
      unknown. To better understand factors influencing the course of disease, HIV-1
      disease progression was explored in terms of declines in CD4 counts. Two samples
      from Nairobi, Kenya, were studied, one from a cohort of female sex workers and
      another, as a comparison group, from mothers enrolled in an HIV-1 vertical
      transmission study. A Markov model was used to analyze transitions between HIV-1
      disease stages as defined by CD4 counts. It appears that sex workers experience a
      rapid decline in CD4 counts, consistent with earlier findings of rapid clinical
      disease progression among individuals in this group. The rate of decline in CD4
      counts among the mothers appears to be lower. It is speculated that either
      intensive exposure to sexually transmitted pathogens or infection with several
      strains of HIV-1 may account for the rapid disease progression among female sex
      workers.

PMID- 7583444
TI  - Evidence for a shift from a type I lymphocyte pattern with HIV disease
      progression. Hemophilia Growth and Development Study.
AB  - Whether a shift from a type I (cell mediated) immune profile occurs with
      progressive HIV-related immune dysfunction is a matter of heated debate. We
      analyzed data for 333 HIV antibody-positive (HIV+) and -negative (HIV-)
      hemophilic children/adolescents, to examine whether the relationships among
      immunologic parameters and vaccine-related serology supported a shift with
      advancing HIV infection. In stepwise logistic regression analysis of HIV+
      children's data, anergy to a panel of delayed hypersensitivity skin test antigens
      was positively associated with serum immunoglobulin A (IgA) levels (p = 0.012)
      and CD8+ cell counts (p = 0.021) and negatively associated with CD4+ cell counts
      (p = 0.002). Modeling supported anergy as a positive correlate of log IgA level
      (p = 0.046) and CD4+ lymphocyte count as a negative correlate, for HIV+
      participants only (p < 0.0001). For mumps, the proportion of vaccinated HIV+
      participants with protective IgG antibody titers was higher among those with CD4+
      lymphocyte counts < 200 cells/mm3 (p = 0.058). For HIV+ participants < 14 years
      of age, this same trend was seen for measles and rubella, but was not seen in any
      age group for bacterial vaccine antigens. The intercorrelations among skin test
      anergy, CD4+ lymphocyte counts, serum IgA levels, and viral vaccine antigen
      related serologic titers for HIV+ participants are consistent with an association
      between progressive HIV-related immune dysfunction and a predominance of type II
      (humoral immunity) or Type 0 (mixed immunity), relative to type I, lymphocyte
      profiles.

PMID- 7583445
TI  - Dynamics of risk behavior for HIV infection among young Thai men.
AB  - The objective of this investigation was to analyze the dynamics of risk for HIV-1
      infection among young men in Thailand. We conducted a prospective study in a
      cohort (n = 1,236) of young men, aged 19-23 years at conscription into the Royal
      Thai Army and Air Force from six provinces in northern Thailand in May 1991 who
      were followed until their discharge in April 1993. The outcome measure was change
      since conscription in the frequency of self-reported sex with female commercial
      sex workers (CSW) during military service. Although 42% of conscripts reported no
      visit to a female CSW in the year prior to conscription, most had a visit during
      military service. Men who visited female CSWs infrequently at baseline increased
      their visits somewhat over time, whereas those with high initial rates of CSW
      visits decreased. Based on an assumed stable distribution over time, change from
      baseline was not statistically significant. Only marital status and high baseline
      CSW visit rates were associated with diminished visit frequency in multivariate
      analysis. No differences were seen in patterns of change in CSW visits by HIV-1
      serostatus. More aggressive preventive interventions are needed to reduce the
      frequency of CSW visits in northern Thailand, a setting where 40-80% of all
      female CSWs working in brothels are now HIV seropositive.

PMID- 7583446
TI  - Accuracy of a saliva test for HIV antibody.

PMID- 7583447
TI  - Recent trends in Pneumocystis carinii pneumonia as AIDS-defining disease in nine
      European countries.

PMID- 7583448
TI  - Seroprevalence of HIV-1 among pregnant women at Recife, northeastern Brazil.

PMID- 7583451
TI  - Increased expression of DNA cointroduced with nuclear protein in adult rat liver.

PMID- 7583449
TI  - Retrovirus-mediated transfer of MHC class II cDNA into swine bone marrow cells.

PMID- 7583453
TI  - Insertion/deletion polymorphism in the angiotensin-converting enzyme gene
      associated with macroangiopathy and blood pressure in patients with non-insulin
      dependent diabetes mellitus.
AB  - In the search for new risk factors for diabetic macroangiopathy the
      insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene
      was studied in 237 consecutive patients (125 men and 112 women) with non-insulin
      dependent diabetes. The female population showed an excess of ischemic
      electrocardiographic changes or definite myocardial infarctions in the patients
      homozygous for the deletion [D/D; odds ratio (OR) 2.8; 95% confidence interval
      (CI) 1.4-5.3] and in the insertion/deletion heterozygotes (I/D; OR 1.8; CI 1.1
      3.1) compared with the patients homozygous for the insertion (I/I). In the total
      series coronary heart disease, cerebrovascular disease, and claudication were
      more often observed in the patients with I/D (OR 1.5; CI 1.0-2.2) or the D/D
      genotype patients (OR 1.7; CI 1.1-2.6) than in those with the genotype I/I. The
      systolic blood pressure was lower in patients with genotype I/I (138 +/- 19 mmHg)
      than in those with the genotype I/D (149 +/- 22 mmHg) or D/D (150 +/- 21 mmHg; P
      < 0.02). The prevalence of hypertension and the median urinary albumin excretion
      rate also tended to be lowest in the I/I genotype patients. Multiple logistic
      analysis revealed that in women the angiotensin-converting enzyme D/D genotype is
      independently associated with coronary heart disease. Our findings suggest that
      variation at the angiotensin-converting enzyme gene locus is one of the factors
      involved in the predisposition of diabetic patients to the development of
      arterial disease and hypertension.

PMID- 7583452
TI  - Genetic mapping of adrenergic receptor genes in humans.
AB  - We have genetically mapped the genes encoding four human adrenergic receptors
      (ARs) of subtypes alpha 1C, alpha 2A, alpha 2B, and beta 1, which are prototypic
      G protein coupled receptors that mediate the physiological effects of
      neurotransmitters, hormones, and drugs. We placed these genes onto the
      Cooperative Human Linkage Center (CHLC) and Genethon framework maps, within
      confidence intervals with greater than 1000:1 odds. With multipoint analysis the
      alpha 1C gene (locus ADRA1C) mapped to the interval between NEFL and D8S283;
      alpha 2-C4, the gene encoding the alpha 2C AR (locus ADRA2C), mapped to the
      interval between D4S126 and D4S62; and the alpha 2-C10 (alpha 2A AR)/beta 1
      haplotype (loci ADRA2A/ADRB1) mapped to the interval between D10S259 and D10S187.
      A fifth AR gene, beta 2, yielded significant LOD scores with markers on the long
      arm of chromosome 5; however, this locus (ADRB2) could not be mapped to any
      specific interval with odds of greater than 1000:1. The two AR genes that are
      completely linked, alpha 2-C10 and beta 1, were oriented on their shared 225-kb
      genomic fragment relative to the direction of transcription, with beta 1 being 5'
      to alpha 2-C10. The positioning of these genes on high-density framework maps
      allows them to be tested as candidates in a spectrum of diseases that might
      involve AR dysfunction.

PMID- 7583450
TI  - A defective HIV-1 vector for gene transfer to human lymphocytes.

PMID- 7583456
TI  - [Evolution of human anti-rabies vaccines from Pasteur to the present].
AB  - Since the first immunization of man against rabies in 1885 by Louis Pasteur,
      antirabies vaccine has been continuously improved. Treatment failures, clinical
      infections by the fixed virus, neuroparalytic accidents in connection with myelin
      were progressively eliminated. Vaccines can be standardized and accurately
      controlled. After the original spinal cord, adult or newborn animals brains,
      embryonated eggs, primary tissue cultures, diploid and permanent cell lines have
      been used for the vaccine production. Today, safe and potent vaccines are
      available. New products might be developed from the technology of genetic
      recombinants.

PMID- 7583457
TI  - [Epidemiology and campaign against rabies in France and in Europe].
AB  - The red fox (Vulpes vulpes) is the reservoir and vector of rabies in Western
      Europe. Field trials to vaccinate it with vaccine-baits dispatched in the fields
      were carried out in Switzerland since 1985. When repeated twice a year in Spring
      and Autumn, for at least two years successively, this method was proven to be
      more efficacious to eliminate rabies than the destruction of fox population by
      shooting or gassing. Since 1986, the same technique was used and adapted in
      France with baits carrying various vaccines. By establishing an immunological
      barrier from the English channel to the national border with Switzerland more
      than 630 km long and 35 to 80 km wide, the advance of the disease towards south
      was stopped. During the following years, the vaccination plan has been extended
      to cover the whole contaminated area in France (at most: 141,700 km2). From 1989
      to 1994, the rabies incidence has been decreased by 98%. Elimination of rabies in
      France is now depending on the treatment of the disease in the neighbouring
      countries. At least, 13 other European countries are vaccinating foxes against
      rabies. Currently over 14 million vaccine baits are dropped annually from
      aeroplanes or distributed by hunters. As a result of oral immunisation there has
      been a sharp decrease in the number of rabies cases in animals in Western Europe.
      A complete elimination of rabies has been achieved over large areas, where
      vaccination is no longer needed. Summing up the results of oral vaccination
      programs carried out in Europe, it appears that reinfections have occurred due to
      various causes: budgetary restrictions limiting either the number of campaigns or
      the size of the possible vaccination zones and also cross-border contamination.
      Today the clearing of the western European peninsula from to east appears
      technically possible but the increase of fox population, and the cost of these
      operations are new challenge to tackled.

PMID- 7583458
TI  - [Laparoscopic cholecystectomy. Technique and complications. Report of 2,665
      cases].
AB  - Retrospective study of 2,665 laparoscopic cholecystectomies (LC) performed
      between April 1988 and December 1994 in the French technique with selective intra
      operative cholangiography. Obesity was present in 13% of patients, respiratory
      insufficiency in 4%, inflammation in 13% and common bile duct (CBD) stones in 4%.
      Those cases are now good indications for L.C. A conversion to laparotomy occurred
      in 52 cases (2%). The rate of post operative complications was 1.6%, including 24
      non biliary complications with 2 death and 17 biliary ones concerning the CBD in
      6 cases. Those results compare favourably with the ones of open cholecystectomy
      and the cost is about the half.

PMID- 7583454
TI  - Inositol phosphates in the heart: controversy and consensus.
AB  - Numerous studies have addressed various aspects of inositol phosphate release and
      metabolism in myocardial preparations, and many different viewpoints have been
      expressed. The various results and interpretations presented often appear
      confusing and extracting a consensus view can be difficult. The differences often
      derive from the differing cardiac preparations used, especially isolated cells
      versus intact tissue. Despite these problems there are aspects where consensus
      prevails. Both the metabolism and the functional activity of inositol phosphates
      in heart appear to differ from those previously described in non-excitable cells.
      Inositol phosphates do not appear to be of major importance in the control of
      cardiac function under physiological conditions but may well have greater
      influence under pathological conditions such as myocardial ischaemia and
      reperfusion. Hopefully, the near future will see remaining controversies
      resolved.

PMID- 7583455
TI  - [Introduction to the commemorative session of the centennial of the death of
      Louis Pasteur].
AB  - When elected a member of Academie de medecine in 1873, Pasteur was well known for
      his achievements in chemistry, fermentation and silk worm diseases. He denied
      spontaneity of diseases, their cause are living germs. Passionate disputations
      took place in Academy on subjects of septicaemia, childbirth fever, or fowl
      cholera. In 1881, his success was obtained by vaccination of sheep against
      epidemic anthrax: his method of virus action softening was available for many
      human infections diseases, in spite of many disputations. The same method applied
      to rabies gave him universal glory. When he died in 1895, his views on infections
      diseases were accepted by Academie de medecine and all over the world.

PMID- 7583460
TI  - [Beta-D-mannosidase].
AB  - Among the lysosomal hydrolytic enzymes, and especially the exoglycosidases which
      carry out the degradation of the glycan moieties of glycoconjugates, the beta-D
      mannosidase (beta-MAN) was the least investigated, up to the discovery of the
      inherited deficiency, in 1979-1980 for the caprine disease, and in 1986 for the
      human one. The beta-mannosidosis is characterized by mental retardation in
      children and by severe osteoarticular damage in kids. In both cases occurs the
      storage of oligosaccharides which are later excreted in urine: beta-mannosyl (1
      4)-N-acetyl-beta-glucosaminyl (1-4)-N-acetylglucosamine, and beta-mannosyl (1-4)
      N-acetylglucosamine in caprine disease, but only the last disaccharide in human
      patients. Having previously studied the serum enzymes, we report here the results
      obtained in the study of human urinary and renal beta-MAN. In each case we
      observed the existence of two isoforms of enzyme, B and a more acidic one, A. The
      main properties of these forms were determined, showing that A form of either
      origin seems to be identical, as well as the B form. But the ratios of activity
      B/A are inverted: 0.2-0.3 in urine, versus 15-20 in kidney. This observation led
      to the examination of the urinary enzyme of patients after a kidney
      transplantation. The B form is the major one, with a B/A ratio of around 3. The
      two isoforms are respectively identical to the normal renal and urinary ones.
      This shows that the B isoform determination way be used as reflecting a renal
      tubular damage.

PMID- 7583461
TI  - [The Royal Society of Medicine, harbinger of occupational medicine and
      ergonomics].
AB  - During her short life (1776-1793), the Royal Society of Medicine of Paris brought
      forth which will become Occupational Medicine. It was indeed at the meetings of
      the Royal Society that Fourcroy presented in 1776 the french translation of "De
      morbis artificum diatriba" from Ramazzini (1701), with introduction and notes
      showing evolution of knowledge. Then, from 1779 to 1793, corresponding fellows
      physicians, manufacturers, inspectors, showed professional diseases, prevention's
      means, learning's methods and diffusion's possibilities. Those impulses, too
      early stopped, will be born again during the XIX th. century and will arrive with
      Devoto in 1901 to the first using of a specific expression which will be in
      italian "Medicina del Lavoro".

PMID- 7583459
TI  - [Effects of morphine on murine infection with Friend retrovirus].
AB  - The immunomodulatory effects of opiates can modify host defenses against
      infection. We investigated the mechanisms involved in these effects by studying
      the influence of morphine on the pathogenesis of murine Friend retrovirus
      infection. The response to this opiate varied greatly according to the treatment
      schedule. Daily intra-peritoneal administration of morphine (50 mg/kg) for 16 to
      27 days attenuated pathological manifestations in infected animals without
      modifying the mortality rate. The protective effect increased proportionately
      with the duration of treatment, and depended on the time of treatment initiation
      relative to inoculation. Naloxone (10 mg/kg/day i.p.) inhibited the morphine
      induced decrease in both splenomegaly and viral titer. Mifepristone--a
      glucocorticoid receptor inhibitor--had no significant effect on the morphine
      induced attenuation of splenomegaly. The influence of the infection on acute
      morphine toxicity was also analysed, using a non lethal dose in noninfected mice
      (200 mg/kg). Susceptibility to morphine increased in parallel to the development
      of the infection, with mortality rates ranging from 20% on D14 to 90% on D21.
      Simultaneous administration of naloxone (20-100 mg/kg) reduced the mortality rate
      and postponed death. Administration of mifepristone, terfenadin, phentolamine or
      propranolol did not modify mortality at the used doses. These findings show that
      the influence of morphine on the development of Friend virus infection in mice
      depends on the conditions of administration. The transient protective effect seen
      in certain conditions of administration seems to be due essentially to the direct
      effects of morphine on its specific receptors.

PMID- 7583462
TI  - [Reform of Title II, Book III of the Public Health Code: campaign against
      venereal diseases].

PMID- 7583463
TI  - [Presentation of the session on the theme: epidemiologic studies and their
      coordination].

PMID- 7583464
TI  - [Sentinel networks. The national public health network. State information].
AB  - In the area of health, the information system used by the authorities is based on
      a series of networks that need to be coordinated. 1. State information: State
      information as regards health epidemiology was for a long time fragmented. The
      reasons for this relative ignorance are varied, and are based both on
      professional and technical factors (preference of physicians for personal
      exchange rather than for statistical analysis, difficulties in data collection
      and mathematical processing), and on socio-political factors (the euphoria of
      years of economic growth). For a long time only the causes of death were
      appropriately documented (cf. Mme Facy's report). In the last decade, a variety
      of initiatives has been directed towards all fields, and morbidity is becoming
      better defined thanks to the ORS (Regional Health Observatories) (cf. M. Garro's
      speech) and health registers (cf. M. Schaffer). Warning systems are becoming a
      principal preoccupation for most people in positions of authority, and explain
      the proliferation of surveillance networks. 2. Sentinel networks: A 'sentinel
      network' is an interactive surveillance system involving the collection of health
      data on a routine basis by a group of doctors (general physicians, biologists,
      etc.). Initially conceived for the surveillance of communicable diseases, they
      are also used for all diseases requiring early warning and rapid intervention
      (effects of sudden pollution, surveillance of drugs and poisons, etc.). These
      sentinel networks have expanded in our countries to complement the compulsory
      notification systems for infectious diseases, whose 'passive' nature often leads
      to under-notification (and therefore a non-representative selection) and delayed
      notification of cases, and whose range of influence does not cover all
      communicable diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583465
TI  - [Role of INSERM in descriptive epidemiologic studies].
AB  - The foundation of INSERM and its development over the past 30 years have led to
      the formation of a public body known in France as EPST. With scientific and
      technological interests, the general aim is to promote the advancement of science
      and to improve the diffusion of information among scientists, teachers or
      decision-makers and also the general public. Epidemiology counts among the
      medical disciplines which are methodologically well developed and widely used by
      many health sectors from clinical research to public health. In the face of more
      stringent social demands, there is a great need for appropriate use and
      exploitation of knowledge and resources. In this context, epidemiological
      research is acquiring a great importance in the production of medical information
      and also in the evaluation of health practices. A good example is provided by the
      epidemiological studies on drug abuse which, in spite of the restrictions,
      furnish new information regarding this problem. 1. Epidemiological studies are
      limited by legislation (Public Health Code). The Mortality Bureau (INSERM) is
      charged with the establishment of a register of the medical causes of death. 2.
      Research proposals are provided by the scientific community. 3. Evaluation
      studies are most often requested by the Ministry of Health, but, more and more
      frequently, may originate in other ministerial offices and local governing
      bodies. The role of the researcher in relation to external collaborations
      (politicians, administrators and consumers) should be precisely defined.

PMID- 7583466
TI  - [Role of regional health observation posts: structure, operation, actions].
AB  - The ORS were established at the beginning of 1980's to improve and to promote
      health informations to help decision makers. The ORS are non-profit making
      institutions supported by Health Ministry and local authorities. They also
      conclude contracts with private or public partners. A national federation exist
      since 1988. The ORS use a lot of scientific technics but have the constant
      preoccupation to adapt their communication for decision makers and non
      specialised public. From 1989 to 1994, more than 900 works have been published on
      a large variety of topics. In 1994, all of the ORS produced a "regional dashboard
      on health" according to a pattern elaborated by their national federation. In
      each region, these documents present most of the available indicators on health
      and social reality. So, the ORS associate local and national points of view.

PMID- 7583468
TI  - [Eulogy of Rene Truhaut (1909-1994)].

PMID- 7583467
TI  - [Role of cancer registries].
AB  - The first Cancer Registries were created in 1975 in France. Their ulterior
      development and their scientific production have been furthered by the apparition
      from 1986 under the aegis of the Health Ministry and of the INSERM, of a National
      Population Registry Committee. Cancer Registries have seriously contributed to a
      better knowledge of the cancer problem in our country and to describe the french
      specificities, in particular the importance of the mouth and pharynx cancers.
      They insure both a monitoring and an alert role; they also contribute to the
      medical supervision of the Chernobyl accident effects. French registries play a
      very active role concerning clinical research. They participate to many European
      studies of health care evaluation. In other respects, many etiological studies
      have been realized about professional risks of cancer, risks linked with
      nutritional habits, and on the etiologic role of the Tamoxifen. Finally, certain
      registries have created DNA banks. If nowadays their role in health planning
      remains modest, they very actively contribute in evaluating screening actions of
      breast, cervix and large bowel cancers. They also attracted the attention of
      Health Authorities on the cervix cancer screening's incoherencies. They evaluate
      the pilot project of the breast cancer and the registry of the Cote d'Or country
      evaluates the efficacity of a randomized colo rectal mass screening study. The
      main difficulties met by the registries are linked with the development of laws
      protecting more and more the individual freedoms, making it harder and harder the
      registration exhaustive character.

PMID- 7583469
TI  - [Drinking water for troops in the field].
AB  - To provide for Armed Forces' water wants, drinking water is only used. Its
      production is not an easy thing in military operations. Armed Forces must use
      their own production means. Four new individual and collective field purification
      systems adapted to manpower, will been soon in use in the French Army. Filtration
      or distillation processes always with chlorine addition are used. The results
      give satisfaction in bacterial epuration; nevertheless chemical and nuclear risks
      are not controlled except in case of distillation mechanism associated with ion
      resins exchanging and charcoal filtration.

PMID- 7583470
TI  - [Epidemiology and prevention of cancer: reflections on the ethics of public
      health measures].
AB  - About 5 million cancer deaths occur each year in the world, and many more cancer
      incident cases arise. It is estimated that at least 80% of these cancers could be
      avoided, based upon currently available epidemiological knowledge. Such a result
      could be achieved through modification of life-style and, to a much lesser
      extent, of the general environment. Therefore, prevention of cancer is a
      realistic and attainable goal. Two complementary approaches can be envisaged. The
      first would be an holistic enterprise aiming at health promotion in general. This
      can be achieved by adopting a life-style favourable to physical, moral and social
      well-being and consists of avoiding recognized cancer risks by the elimination of
      smoking, moderation in alcohol consumption, modification of diet and the
      suppression of occupational and environmental carcinogens. Public health
      programmes must be set up as soon and as widely as possible and should be
      directed primarily at children and be seriously evaluated. Doctors and health
      professionals have a major role to play in this important effort. By contrast,
      pharmacoprevention is only at a preliminary research stage. With the exception of
      immunization which has demonstrated its efficacy in infectious diseases and looks
      promising for the prevention of virus-associated cancers, other proposed
      chemopreventive agents are not yet ready for use in the population at large.
      Vitamin supplementation and particularly antihormones have been proposed for the
      prevention of cancers. Potential or demonstrated iatrogenicity of these products
      preclude large scale use and ethical questions remain unanswered, even within the
      context of research projects.

PMID- 7583471
TI  - Holding the line against wrong-headed changes.

PMID- 7583473
TI  - Attention-deficit hyperactivity disorder and comorbid substance use disorders in
      adults.

PMID- 7583472
TI  - What's a family to do?

PMID- 7583474
TI  - Psychiatric kibitzing.
AB  - Foreword from Dr. Sharfstein: In this era of managed care, utilization review,
      and concerns about costs, a clinician-reviewer who knows little about a case may
      make a decision that profoundly affects the course of a patient's treatment.
      Although Dr. Houghton's timely essay does not involve a managed care or
      utilization reviewer, it serves to remind us about the dangers inherent in
      criticizing the work and the judgment of other clinicians.

PMID- 7583475
TI  - Redefining the general psychiatrist: values, reforms, and issues for psychiatric
      residency education.
AB  - The structure and content of general psychiatric residency education must be
      redesigned to ensure the continued relevance of the profession of psychiatry as
      managed care and cost containment become more influential in the health care
      delivery system. The general psychiatrist in this new health care environment
      must be prepared to participate in a multidisciplinary team of health care
      professionals, have expertise in treating complex cases that often combine
      physical and psychological disorders, critically examine the role of
      psychotherapy, acknowledge patients as active participants in treatment, and
      integrate clinical and financial decision making. Reformed psychiatric residency
      curricula should include an expanded range of training settings, preparation for
      a variety of clinical roles, practice in developing strategies for improved
      service utilization, and opportunities to develop expertise in
      neuropsychopharmacology, to work with patients with serious mental illness, and
      to practice integration of psychotherapy with other core skills. In addition,
      redesigned curricula should enhance residents' appreciation of the interaction
      between patients' everyday behavior and mental illness and should provide
      training in supervision and in utilization review. Redefinition of the structure
      and organization of psychiatric residency education will depend on the resolution
      of several key issues such as length of training, financing of graduate medical
      education, and the role of subspecialization programs.

PMID- 7583476
TI  - Contact between psychotherapists and psychiatric residents who provide medication
      backup.
AB  - OBJECTIVE: Psychiatric residents frequently prescribe medication for patients who
      are in psychotherapy with another clinician. This study examined the extent and
      characteristics of communication between psychiatric residents and
      psychotherapists who treated patients in a university outpatient clinic. METHODS:
      Thirteen psychiatric residents who prescribed medications for 83 patients seen by
      other clinicians for therapy were surveyed about whether and how often during a
      five-month period they had contact with the therapist, who initiated the contact,
      and whether it took place with the patient's consent. Patients' charts were
      reviewed to determine if contacts were documented. RESULTS: The psychiatric
      residents indicated they had contact with the therapist in 44 of 83 cases (53
      percent). Contact was initiated by the prescribing psychiatrist in 47.7 percent
      of the cases and by the therapist in 43.2 percent of the cases. The charts of
      only seven patients (8.4 percent) included written documentation of contact.
      CONCLUSIONS: Several steps are necessary to optimize communication between
      treating clinicians and documentation of such communication. They include initial
      contact to discuss the treatment contract and clarify each clinician's
      responsibilities, formal written consent from the patient, regular contacts
      between clinicians to discuss the patient's progress, and collaboration between
      clinicians on the patient's treatment plan.

PMID- 7583477
TI  - A national survey of the use of outpatient commitment.
AB  - OBJECTIVE: To determine the extent of use of outpatient commitment, a survey was
      undertaken of each state and the District of Columbia. METHODS: One of the
      authors, an attorney, reviewed pertinent state statutes, then conducted telephone
      interviews with individuals in each state who were knowledgeable about the use of
      outpatient commitment. RESULTS: Thirty-five states and the District of Columbia
      have laws permitting outpatient commitment. Georgia, Hawaii, and North Carolina
      use different criteria for outpatient commitment than for inpatient commitment.
      In only 12 states and the District of Columbia was use of outpatient commitment
      rated as very common or common. Reasons for not using it include concerns about
      civil liberties, liability, and fiscal burden as well as lack of information and
      interest, the failure of some states to set enforceable consequences for
      noncompliance, and criteria that are too restrictive. Some states use alternative
      formal or informal mechanisms to encourage treatment compliance; conditional
      release is widely used in New Hampshire and conservatorship-guardianship in
      California. Within many states the availability of outpatient commitment varies
      considerably by locale. CONCLUSIONS: To clarify the role of outpatient commitment
      in psychiatric services, more research is needed to identify optimal candidates
      for its use. Research is also needed on its overall effectiveness compared with
      conditional release and conservatorship-guardianship and on the consequences of
      not using such mechanisms to improve treatment compliance.

PMID- 7583478
TI  - Characteristics of violence in the community by female patients seen in a
      psychiatric emergency service.
AB  - OBJECTIVE: This study examined differences in factors associated with violence
      toward others by female and male patients evaluated in a psychiatric emergency
      service. METHODS: A sample of 812 psychiatric patients recruited in the emergency
      service of an urban psychiatric hospital were followed in the community over a
      six-month period. Patients provided self-reports of violent incidents, and
      collateral informants also provided reports of the incidents. Official records
      were also reviewed. During the followup period, 369 patients (213 male and 156
      female patients) engaged in violence, defined as laying hands on another person
      in a threatening manner or threatening another person with a weapon. RESULTS:
      Male and female patients did not differ significantly in frequency and
      seriousness of violence, but they did differ on who the co-combatant was and
      where the incident took place. CONCLUSIONS: Gender is not a strong predictor of
      involvement in violence by psychiatric patients. The observed gender differences
      in location in which violence took place and identity of the co-combatant may be
      related to differences in the social worlds of men and women, with men having
      more opportunity for public violence with strangers.

PMID- 7583479
TI  - State psychiatric hospital patients with past arrests for violent crimes.
AB  - OBJECTIVE: This study examined associations between four types of major
      psychopathology--schizophrenia, schizoaffective disorder, and bipolar and
      unipolar affective disorders--and history of violent crime. The effects of
      demographic variables, substance abuse, psychosis, and paranoia on history of
      violent crime were also determined. METHODS: Diagnostic assessments using the
      Schedule for Affective Disorders and Schizophrenia and Research Diagnostic
      Criteria identified 172 state hospital inpatients with the four diagnoses of
      interest, as well as those with co-existing substance use disorders. Based on
      arrest records, patients were categorized according to the most violent crime for
      which they had been arrested. RESULTS: Patients with schizoaffective disorder
      were significantly more likely than those in the other diagnostic groups to have
      been arrested for a violent crime. Similar results were found for psychotic
      patients compared with nonpsychotic patients, patients who had paranoid
      schizophrenia compared with patients who had schizophrenia without paranoid
      features, and patients who had co-existing substance abuse compared with those
      with no history of substance abuse. Patients from racial minority groups and male
      patients were also more likely than white patients and female patients to have
      been arrested for a violent crime. CONCLUSIONS: Demographic features, a diagnosis
      of schizoaffective disorder, psychosis, paranoid symptoms, and substance abuse
      may all be associated with violent behavior.

PMID- 7583480
TI  - Characteristics of state hospital patients arrested for offenses committed during
      hospitalization.
AB  - OBJECTIVE: The study was a preliminary exploration of the relatively new
      phenomenon of arresting psychiatric inpatients for offenses committed in the
      hospital. METHODS: A retrospective record review at two New York state hospitals
      identified all 73 inpatients arrested over a 30-month period for an offense
      committed while they were hospitalized. Logistic regression was used to compare
      arrestees with a control group of 1,438 non-arrested inpatients. RESULTS: The
      number of arrests at the two hospitals significantly increased over the study
      period. Seventy-nine percent of arrests resulted from a violent incident. At
      least 68 percent of arrestees had been arrested previously. Compared with the
      control group, arrestees were more likely to be young, male, and black and to
      have a shorter length of stay. Axis I diagnoses did not differentiate arrestees
      from control patients. Ninety percent of arrestees had a diagnosis of substance
      use or personality disorder or both. The sample more closely resembled the
      population of criminal offenders in the community than the psychiatric inpatient
      population. Prosecution resulted in jail or prison terms for 11 percent of
      arrestees. CONCLUSIONS: This descriptive preliminary study was limited by its
      retrospective nature and reliance on records of varying quality. Although the
      increase in arrests is clear, the cause of the increase and the impact of arrests
      on arrestees and hospitals remain to be clarified.

PMID- 7583481
TI  - Effects of stringent criteria on eligibility for clozapine among public mental
      health clients.
AB  - OBJECTIVE: This study estimated rates of eligibility for treatment with clozapine
      among clients in a public mental health system using criteria with various
      degrees of restrictiveness. METHODS: A stratified, random cluster sample of 293
      clients was selected from among all clients with schizophrenic disorders known to
      the mental health system of the city and county of San Francisco during 1991.
      Data on variables associated with eligibility for clozapine were abstracted from
      clinical records, and eligibility was estimated using broad and stringent
      criteria. RESULTS: An estimated 42.9 percent of the clients were eligible for
      clozapine using broad eligibility criteria that included a diagnosis of
      schizophrenia or schizoaffective disorder, two previous neuroleptic trials of at
      least 600 mg per day chlorpromazine equivalents for at least four weeks or
      tardive dyskinesia, Global Assessment of Functioning score less than 61, and no
      contraindications. Eliminating eligibility due to tardive dyskinesia alone,
      excluding persons with schizoaffective disorder, requiring six-week medication
      trials, and requiring three adequate medication trials instead of two resulted in
      substantial reductions in the rate of eligibility. CONCLUSIONS: Varying
      interpretations of the criteria for clozapine treatment listed in the medication
      package insert dramatically affect patients' eligibility for clozapine. Mental
      health agencies should endeavor to maintain a balance between restricting use of
      clozapine due to cost and providing it to the full spectrum of patients who might
      benefit from the medication.

PMID- 7583482
TI  - A survey of an organization for families of patients with serious mental illness
      in The Netherlands.
AB  - OBJECTIVES: Members of Ypsilon, a Dutch family organization for relatives of
      patients with schizophrenia or chronic psychosis, were surveyed to determine
      whether patients whose families were involved in the organization were
      representative of all patients with schizophrenia in the Netherlands and whether
      Ypsilon was similar to family organizations in other countries, to learn about
      members' experience of the course of their relatives' illness, to determine the
      kinds of mental health care received by the patients, and to discern members'
      opinions of that care. METHODS: An extended version of the Involvement Evaluation
      Questionnaire, which measures consequences of psychiatric disorders for patients'
      relatives, was sent to a random sample of 1,000 Ypsilon members. The response
      rate was 70 percent. RESULTS: Members of Ypsilon are mainly older mothers of
      young male patients with a long history of schizophrenia. The patients as a group
      appeared to be more severely ill than the overall population of patients with
      schizophrenia in the Netherlands. Many respondents reported dissatisfaction with
      the quality of mental health care for their relative, particularly with their
      lack of access to treatment professionals, lack of information about their
      relative's illness, and lack of family involvement in treatment planning.
      CONCLUSIONS: Members of Ypsilon represent patients with severe mental illness who
      do not benefit sufficiently from treatment. Members want a greater role in
      treatment planning and more information and support from mental health care
      professionals. Members of Ypsilon and of family organizations in other countries
      have much in common, even though the extent of deinstitutionalization varies
      between countries.

PMID- 7583484
TI  - Cost-effective communication skills training for state hospital employees.
AB  - OBJECTIVE: This study evaluated the cost-benefits of a staff communications
      training program designed to improve patient management skills and relieve staff
      stress. METHODS: The interpersonal communications program, based on the Carkhuff
      model, was specially designed for mental health settings. The training program
      focused on developing accurate empathy by teaching staff members to use
      appropriate cognitive and emotional components of interpersonal communication.
      Staff on a short-stay adult inpatient recidivist unit received the training,
      while those on a matched unit served as a quasi-control group. Data from routine
      reports from six months before and six months after training were analyzed. The
      main cost-benefit variables of interest were improved staff retention and patient
      outcomes. RESULTS AND CONCLUSIONS: The trained unit had less staff turnover, and
      staff members on that unit used less sick and annual leave. Fewer patients'
      rights complaints were filed, and fewer assaults on staff were reported. The cost
      benefit analysis revealed substantial savings for the trained unit and increased
      expenditures for the control unit. The results suggested that training in
      empathic communication skills for direct care staff is a promising proactive,
      cost-effective approach to coping with staff stress and turnover and may also
      improve patient outcomes.

PMID- 7583483
TI  - Predictors of high and low levels of HIV risk behavior among adults with chronic
      mental illness.
AB  - OBJECTIVE: Several recent studies confirm elevated rates of human
      immunodeficiency virus infection among acute and chronic mentally ill adults in
      large urban areas. This research sought to characterize risk for HIV infection
      among adults with chronic mental illness and to examine psychosocial factors
      predictive of risk. METHODS: Two hundred and twenty-five adults with chronic
      mental illness who were sexually active in the past year outside of exclusive
      relationships were individually interviewed in community mental health clinics
      using a structured HIV risk assessment protocol. RESULTS: More than 50 percent of
      the study participants were sexually active in the past month, and 25 percent had
      multiple sexual partners during that period. Fifteen percent of the men had male
      sexual partners. In more than 75 percent of occasions of sexual intercourse,
      condoms were not used. When participants were categorized as at either high or
      lower risk for HIV infection based on their pattern of condom use, psychosocial
      factors that predicted risk level included measures of participants' self
      reported efficacy in using condoms, perceptions of social norms related to safer
      sex among peers and sexual partners, and expectations about outcomes associated
      with condom use, as well as participants' level of objectively assessed
      behavioral skills in negotiation and assertiveness in sexual situations.
      CONCLUSIONS: Interventions aimed at prevention of HIV and AIDS are urgently
      needed in settings that provide services to persons with chronic mental illness.

PMID- 7583485
TI  - Pathways to mental health care in Nigeria.
AB  - A total of 238 patients who attended a mental health service in Ilorin, Nigeria,
      over a one-month period were interviewed to assess the routes they took to
      psychiatric care. Ninety-five patients reported that they had first contacted
      traditional or religious healers when they became mentally ill. Patients who
      contacted such healers included significantly more males and Muslims and fewer
      patients with professional occupations. Family members played important roles in
      patients' decisions about the type of practitioner to consult. The author
      suggests that use of psychiatric care in developing countries could be improved
      by training primary health care workers to give mental health education to the
      communities they serve.

PMID- 7583486
TI  - Development of an integrated clinical database system for a regional mental
      health service.
AB  - The authors describe development of an automated system to provide caregivers in
      a regional mental health service in Calgary, Alberta, with access to information
      about persons with chronic mental illness served by the system. All participating
      organizations provided input about system design features and data elements.
      Issues of confidentiality of records were addressed. A working model demonstrated
      to caregivers was rated as useful and understandable by more than 90 percent of
      respondents.

PMID- 7583487
TI  - Six cases of patients with mental retardation who have antisocial personality
      disorder.
AB  - Evidence that antisocial personality disorder occurs in association with mental
      retardation is presented through case reports of six mildly to moderately
      retarded men who received a diagnosis of antisocial personality disorder. The men
      were identified when referred by care providers for more thorough psychological
      and psychiatric assessments. Their histories were marked by thefts, rapes,
      multiple assaults, arson, and other predatory acts; a lack of remorse for such
      actions; criminal charges; and predisposing factors such as an impoverished
      family. Only one man had received the diagnosis of antisocial personality
      disorder before the assessments, suggesting that clinicians are reluctant to find
      sociopathic behavior clinically significant in the presence of mental
      retardation.

PMID- 7583488
TI  - Parent orientation meetings to improve attendance and access at a child
      psychiatric clinic.
AB  - As one of several strategies to improve attendance and reduce the size of the
      waiting list at a child psychiatric clinic serving urban, multiproblem clients,
      parents were required to attend a free pretreatment orientation group meeting.
      The rate of missed appointments among families not oriented to the clinic was
      compared with that of families who attended the orientation meeting. The
      orientation process significantly improved attendance at intake appointments but
      did not appear to affect attendance at subsequent appointments. It screened out
      unmotivated parents, reduced the size of the waiting list, and allowed greater
      access to clinic services.

PMID- 7583491
TI  - Caregiver burden.

PMID- 7583489
TI  - Treatment of Hassidic Jewish patients in a general hospital medical-psychiatric
      unit.
AB  - A combined medical-psychiatric inpatient unit at a general medical center in
      Brooklyn, New York, provides inpatient psychiatric treatment to members of the
      Orthodox Jewish sect of the Lubavitcher Hassidim, who are generally reluctant to
      accept treatment in traditional psychiatric inpatient settings. The unit's
      biological treatment model, which emphasizes long-term maintenance on
      psychotropic medication, monthly postdischarge pharmacotherapeutic visits,
      lowered expectations, and minimal use of expressive psychotherapy, is compatible
      with the Hassidic community's view of mental illness. A practicing Orthodox
      Jewish psychiatrist on the unit staff sensitizes other staff members to religious
      and cultural issues in treating Hassidic patients.

PMID- 7583492
TI  - Pharmaceuticals and politics.

PMID- 7583490
TI  - Cost-benefits of new drugs.

PMID- 7583493
TI  - Psychiatrists' patients.

PMID- 7583494
TI  - "Boundary busting" and the mentally ill homeless population.

PMID- 7583495
TI  - Studies of the course and outcome of schizophrenia in later life.

PMID- 7583496
TI  - Deinstitutionalization and managed care: deja vu?

PMID- 7583497
TI  - Impact of a managed mental health program on Medicaid recipients with severe
      mental illness.

PMID- 7583498
TI  - A national survey of mobile crisis services and their evaluation.
AB  - OBJECTIVE: Although mobile crisis services have been widely accepted as an
      effective approach to emergency service delivery, no systematic studies have
      documented the prevalence or effectiveness of these services. This survey
      gathered national data on the use and evaluation of mobile crisis services.
      METHODS: In 1993 mental health agencies in 50 states, the District of Columbia,
      and U.S. territories were surveyed. Repeated follow-up was done to ensure a 100
      percent response. RESULTS: A total of 39 states have implemented mobile crisis
      services, dispatching teams to a range of settings. Although respondents reported
      that use of mobile crisis services is associated with favorable outcomes for
      patients and families and with lower hospitalization rates, the survey found that
      few service systems collect evaluative data on the effectiveness of these
      services. CONCLUSIONS: The claims of efficacy made for mobile crisis services,
      which have led to their widespread dissemination, are based on little or no
      empirical evidence. More rigorous evaluation of new and existing modes of service
      delivery is needed. The need for such evaluation will increase in the climate
      promulgated by managed care, in which greater emphasis is placed on cost
      effectiveness.

PMID- 7583499
TI  - Estimated societal costs of assertive community mental health care.
AB  - OBJECTIVE: The study used a societal costs model to estimate costs of assertive
      community treatment for persons with severe mental illness. METHODS: Resource use
      and cost data were collected for mental health, health, social, and law
      enforcement, and other maintenance services and family services for 94 clients
      enrolled in a mobile community treatment program in Madison, Wisconsin. Data
      sources included self-reports of clients and family members, private and public
      agency records, and insurance claims files. To make more precise estimates,
      outcome definitions were broadened, data sources were cross-validated, and prices
      of services were calculated independently of agencies' charges for such services.
      RESULTS: Average societal costs for participants in the study were estimated at
      $23,061 in 1988 ($29,965 in 1994 dollars). Use of a less sophisticated model with
      less careful costing methods would have resulted in an estimated average cost at
      least 30 percent lower. Maintenance costs (cash payments from government
      programs, subsidies, and in-kind services) were the largest cost component,
      followed by mental health treatment, family burden, indirect treatment, and law
      enforcement. Most of the financing for these services came from the public sector
      (85 percent). CONCLUSIONS: Accurate, reliable, and consistent measurement of
      societal costs will aid in the complex task of rationing fixed health and mental
      health care budgets.

PMID- 7583500
TI  - Psychopathology among children placed in family foster care.
AB  - OBJECTIVE: The literature on psychopathology among children in family foster care
      published in the last 20 years was reviewed to estimate prevalence and types of
      psychopathology in this population. METHODS: A comprehensive computerized
      database was searched for the period 1974 through 1994, with emphasis on recent
      literature. RESULTS AND CONCLUSIONS: Available evidence suggests that the
      prevalence of psychopathology among children in family foster care is higher than
      would be expected from normative data, even when this population is compared with
      children who have backgrounds of similar deprivation. As for the types of
      psychopathology in this population, the only apparent trend is the predominance
      of externalizing disorders, such as disruptive behavior disorders. A combination
      of social, psychological, and biological factors may render children in family
      foster care highly vulnerable to psychopathology.

PMID- 7583501
TI  - Command hallucinations and the prediction of dangerousness.
AB  - OBJECTIVES: Recent studies have supported the belief that command hallucinations
      can induce dangerous behavior. This study tried to replicate previous findings
      that compliance with the command was associated with delusions related to
      hallucinations and the ability to identify the hallucinated voice. This study
      also assessed the association between compliance and the dangerousness of the
      command, chronicity of illness, a diagnosis of schizophrenia, and past compliance
      with hallucinated commands. METHODS: The most recent command hallucination
      reported by 93 psychiatric inpatients was rated for level of dangerousness and
      level of compliance with the command. RESULTS: Subjects who experienced less
      dangerous commands or who could identify the hallucinated voice reported higher
      levels of compliance, although reported compliance with more dangerous commands
      was not uncommon. Commands experienced in the hospital were less dangerous than
      those experienced elsewhere and tended to be specific to the hospital
      environment. Subjects were less likely to comply with commands experienced in the
      hospital. CONCLUSIONS: Based on their self-reports, psychiatric patients who
      experience command hallucinations are at risk for dangerous behavior. Ability to
      identify the hallucinated voice is a fairly reliable predictor of reported
      compliance. Level of dangerousness resulting from compliance with command
      hallucinations may be a function of the patient's environment.

PMID- 7583502
TI  - Suicide contagion among adolescents during acute psychiatric hospitalization.
AB  - OBJECTIVE: The study investigated whether exposure to other suicidal adolescents
      led to suicide contagion among patients hospitalized on an acute adolescent
      psychiatry unit. It also examined whether some adolescents express more
      suicidality during hospitalization than before admission. METHODS: Fifty-seven
      adolescents with a range of diagnoses admitted to a university-based psychiatric
      inpatient unit were assessed for suicidality at hospital admission and discharge
      using the Spectrum of Suicide Behavior scale and the Suicidal Ideation
      Questionnaire-Jr. Suicidal intent or behavior was the primary reason for
      admission of 58 percent of the patients. RESULTS: Despite many patients' severe
      suicide risk at hospital admission, 94 percent expressed no active suicidal
      intent and engaged in no behavior that could be considered suicidal during
      hospitalization. Four patients engaged in possibly suicidal, self-cutting
      behaviors; however, these incidents did not cluster in time. Fourteen patients
      (26 percent) expressed a significant increase in suicidal ideation during
      hospitalization, but the increase was not associated with study measures of
      exposure to other suicidal adolescents. CONCLUSIONS: Contagion of suicidal
      behaviors may not be a frequent or significant problem on acute adolescent
      inpatient units, although the phenomenon of increased suicidal ideation among
      some inpatients warrants further study.

PMID- 7583503
TI  - Suicide: the interaction of clinical and ethical issues.
AB  - Although bioethical principles such as beneficence, nonmaleficence, and autonomy
      increasingly guide clinical decision making, in good clinical practice none of
      these principles is absolute. The authors describe how clinical and ethical
      issues interact in prioritizing principles in the treatment of suicidal patients.
      For the acutely suicidal patient, beneficence must be given primacy, as it should
      for the chronically suicidal patient who is unable to control self-destructive
      impulses. However, some chronically suicidal patients may be capable of resisting
      these impulses, and in such situations, respecting patients' autonomy facilitates
      clinical work and prevents the therapist from being drawn into a role that
      encourages regression. The successful management of the suicidal patient
      illustrates the need for dynamic, rather than rigid, application of ethical
      principles.

PMID- 7583504
TI  - Effects of homelessness on the quality of life of persons with severe mental
      illness.
AB  - OBJECTIVE: This study assessed the relationship between homelessness and specific
      quality-of-life problems for persons with severe and persistent mental illness.
      METHODS: The objective and subjective quality of life of 106 homeless persons
      with severe mental illness who lived on the streets or in shelters in Baltimore
      was compared with that of 146 domiciled persons with severe mental illness who
      lived in the community. RESULTS: Objective and subjective quality of life of the
      homeless subjects was clearly worse than that of the domiciled group in the areas
      of living situation, family and social relations, employment, daily activities,
      and legal and safety problems. Homeless subjects were also less likely to have
      federal disability entitlements. CONCLUSIONS: Poorer quality of life is
      associated with homelessness among persons with severe mental illness. Their
      quality of life may be improved by efforts to increase their access to disability
      entitlements and treatment services and to help them develop supportive social
      networks.

PMID- 7583505
TI  - A model for the classification and diagnosis of relational disorders. Committee
      on the Family, Group for the Advancement of Psychiatry.
AB  - Important and common relational conditions, such as severe couple dysfunction and
      family violence involving child or elder abuse, have been omitted from DSM-IV,
      the authors believe. They argue that such conditions can exist independently of
      severe individual psychopathology and that these conditions should be described
      in relational terms, with specific diagnostic criteria. They outline a
      classification of relational disorders and propose its addition to axis I of DSM
      IV. This classification scheme focuses on severe family dysfunction; problems of
      living usually treated by couple and family therapists are intentionally omitted.
      Descriptions of two relational disorders, written in DSM style, are provided. The
      authors discuss implications for the treatment and rehabilitation of patients,
      the future training of psychiatrists, and the direction of research.

PMID- 7583507
TI  - Mental health care needs of female veterans.
AB  - Gender differences in diagnosis, demographic and family characteristics, and
      trauma histories among psychiatric outpatients at a Veterans Affairs clinic were
      examined. Among the 51 women and 46 men, significantly more women had affective
      disorders and schizoaffective disorder; significantly more men had anxiety
      disorders, schizophrenia, and substance use disorders. Although women had sharply
      higher rates than men of every type of trauma except combat trauma, more male
      veterans received a diagnosis of posttraumatic stress disorder. Men were four
      times more likely to be married. Women were more likely than men to be the sole
      caretakers of minor children. These differences have important treatment and
      policy implications. The findings confirm that recently initiated VA programs
      recognize important treatment needs of female veterans.

PMID- 7583508
TI  - Psychiatric morbidity and family burden among parents of disabled children.
AB  - Twenty parents of mentally retarded children and 20 parents of children with
      neurological impairments were interviewed to determine their levels of
      psychiatric symptoms and of subjective and objective burden associated with care
      for their disabled child. The parents of disabled children had significantly
      higher levels of psychiatric symptoms and were more likely to meet criteria for
      depressive disorders, compared with a matched control group of parents of
      children without disabilities. The two groups of parents of disabled children
      reported considerable subjective and objective burden, although there were no
      differences between those groups in the level of burden.

PMID- 7583506
TI  - Diagnosis and hospital readmission rates of female veterans with substance
      related disorders.
AB  - OBJECTIVES: The study examined the prevalence of substance use, psychiatric, and
      medical disorders in female veterans discharged from VA hospitals. METHODS: The
      VA discharge abstract database was used to identify women discharged in fiscal
      year 1991 who received a diagnosis of substance abuse or dependence or substance
      induced psychosis (N = 1,698). They were compared with female veterans who did
      not receive a substance-related diagnosis (N = 12,037). RESULTS: Alcohol and
      cocaine use disorders were the most prevalent substance use disorders. Women with
      substance use disorders were more frequently diagnosed as having personality
      disorders, depression, and posttraumatic stress disorder than women without
      substance use disorders. Skin and subcutaneous tissue diseases, infectious and
      parasitic diseases, and digestive diseases were more prevalent among women with
      substance use disorders than among women in the same age group who did not have
      substance use disorders. Approximately 44 percent of women with substance use
      disorders who were discharged during the first six months of fiscal year 1991
      were rehospitalized within that year. CONCLUSIONS: Substance use disorders and
      associated comorbidities are endemic among women treated in VA hospitals.
      Additional studies examining characteristics of indigent women with substance use
      disorders are needed.

PMID- 7583509
TI  - Postdischarge follow-up of psychiatric inpatients and readmission in an HMO
      setting.
AB  - This study examined the relationship between follow-up and rehospitalization of
      inpatients discharged from treatment in two divisions of a health maintenance
      organization (HMO). Among 580 patients discharged, two-thirds made a follow-up
      visit within 30 days. Slightly less than a third were readmitted within six
      months. Readmission was less likely for patients who made a follow-up visit and
      for men. Patients who had a preadmission relationship with a mental health
      practitioner were more likely to make a follow-up visit and were more likely to
      be readmitted. Follow-up was also associated with diagnoses of adjustment and
      affective disorders.

PMID- 7583510
TI  - Nicotine addiction counseling for chemically dependent patients.
AB  - A total of 771 professionals employed in alcohol treatment programs in Nebraska
      were surveyed to determine whether their personal alcohol and tobacco use status
      or characteristics of their treatment programs were related to whether they
      provided nicotine addiction counseling. About a third of respondents agreed that
      clients in active treatment should be urged to quit smoking. Compared with
      respondents who had never smoked, current smokers were one-half to one-third as
      likely to provide such counseling. Greater knowledge of the effects of nicotine
      addiction and employment in programs that provided nicotine addiction education
      or treatment increased the odds of counselors' providing nicotine counseling.
      Counselors' alcohol use status was not associated with nicotine counseling
      practices.

PMID- 7583511
TI  - Effects of psychosocial rehabilitation for hospitalized mentally ill homeless
      persons.
AB  - The effectiveness of a psychosocial rehabilitation program in preventing further
      hospitalization among a group of hospitalized severely mentally ill homeless
      persons in Israel was evaluated. The program includes inpatient and community
      residential phases designed to help the participants gradually become more
      independent. All clients (N = 98) discharged from the inpatient phases to
      supervised or independent community residences since 1982 were followed until
      December 31, 1992, to determine changes in hospitalization rates. The average
      follow-up time was six years. The percentage of time clients were hospitalized
      dropped from 64.9 percent before discharge to the community residences to 12
      percent between discharge and follow-up.

PMID- 7583512
TI  - Risperidone guidelines.

PMID- 7583513
TI  - Risperidone and NMS?

PMID- 7583515
TI  - Attachments to the hospital.

PMID- 7583514
TI  - Housing options for patients.

PMID- 7583516
TI  - The 21st Meeting of the British Inflammation Research Society, "Inflammatory
      pain", King's College, London, 19th December, 1994.

PMID- 7583518
TI  - The role of non-protein sulfhydryl compounds in gastric adaptive cytoprotection
      against ethanol-induced mucosal damage in rats.
AB  - The contribution of the endogenous nonprotein sulfhydryl compounds (SH) in
      gastric adaptive cytoprotection was investigated in rats. N-ethylmaleimide (NEM)
      treatment significantly reduced mucosal SH level, and aggravated the mucosal
      injury induced by absolute ethanol. Oral administration of the mild irritants,
      20% ethanol, 5% NaCl or 0.3 M HCl, significantly increased the basal mucosal SH
      level. These agents also showed a cytoprotective action against the necrotizing
      effect of absolute ethanol. Administration of NEM did not alleviate this
      cytoprotective potential, although it abolished the increased SH level evoked by
      these mild irritants. Thus, it is concluded that modulation of endogenous SH by
      mild irritants perhaps only plays a minor role in the gastric adaptive
      cytoprotection.

PMID- 7583517
TI  - Spinal opioid systems in inflammation.
AB  - Until recently, basic science studies, both behavioural and electrophysiological,
      have concentrated on the antinociceptive actions of opioids primarily gauged
      against acute nociceptive responses. However, of more relevance to clinical
      situations are the actions of opioids in more persistent/prolonged pain states.
      This review sets out to examine the central actions of opioids against
      nociception of inflammatory origins. The first section deals with the response of
      the endogenous opioid system to the development of an inflammatory state and the
      second examines the ability of exogenous opioids to modulate inflammatory
      nociception. There are complex changes in the roles of endogenous opioids, in
      particular dynorphin, at the spinal level after inflammation although the
      physiological consequences remain unclear. With regard to exogenous opioids, the
      effectiveness of spinal morphine is rapidly enhanced after inflammation, likely
      to be due to changes in the interaction between the peptide cholecystokinin and
      the mu opioid receptor. The ability of inflammatory processes to alter both
      endogenous opioids and morphine analgesia at the spinal level illustrates the
      considerable degree of plasticity observed in opioid function.

PMID- 7583522
TI  - Effect of clodronate on established collagen-induced arthritis in rats.
AB  - The collagen-induced arthritis model in rats was used to study the effect of
      disodium clodronate on inflammation and destruction of tarsal, metatarsal, and
      interphalangeal bones and joints. Female DA rats were immunized with heterologous
      type II collagen. Fourteen days after immunization, rats with similar scores were
      assigned to the different experimental groups. They were treated subcutaneously
      either with saline (controls) or with clodronate at doses of 12.5 and 25
      mg/kg/day five times a week for 2 weeks. Clinical signs of arthritis including
      the severity of paw swelling were assessed weekly. At the time of killing,
      histological features of the non-decalcified tarsus with tarsal, tarsometatarsal
      and interphalangeal joints were assessed for inflammatory soft-tissue, articular,
      and bone changes. All the arthritic control rats developed severe arthritis as
      shown by the total histological scores of the hindpaw. The treatment with
      clodronate (25 mg/kg) decreased clinical signs of arthritis, the activity of the
      collagen-degrading lysosomal enzyme, beta-N-acetylglucosaminidase, in inflamed
      hindpaw tissue, serum osteocalcin level and serum cross-linked telopeptide of
      type I collagen level. Histological evaluation indicated moderate arthritis in
      29% of the rats and severe arthritis in 71%. The results show that clodronate
      given therapeutically to arthritic rats, induced with type II collagen,
      suppresses the intensity of inflammation and bone lesions in the tibiotarsal and
      tarsometatarsal regions.

PMID- 7583520
TI  - Measurement and drug induced modulation of interleukin-1 level during zymosan
      peritonitis in mice.
AB  - The time-course and pharmacological modulation of interleukin-1 (IL-1) production
      were investigated during zymosan induced peritonitis in mice. IL-1 alpha
      liberation was assessed by specific immunoassay (ELISA) and the IL-1 like
      bioactivity (sensitive to both alpha- and beta-forms of IL-1) was measured by a
      sensitive bioassay (D10G4.1 costimulation). I.p. injection of zymosan induced
      significant IL-1 release into the peritoneal exudate. The level peaked at 4 h and
      by 24 h dropped below the detection limit in both assays. The effects of the
      prototypical antiinflammatory drugs indomethacin (IND) and dexamethasone (DEX)
      and that of IX 207-887, a compound which has been reported to interfere primarily
      with IL-1 production, were also tested. DEX and IX 207-887 dose-dependently
      decreased the immunoassayable IL-1 alpha level and the IL-1 like bioactivity as
      well. However, IND had no suppressant effect. Thus, the data obtained by
      immunoassay and bioassay correlated well proving the suitability of zymosan
      peritonitis model for the examination of IL-1 production in experimental
      inflammation.

PMID- 7583519
TI  - Recepto-secretory mechanism in histamine-stimulated amylase release from rat
      parotid gland.
AB  - The recepto-secretory mechanism in histamine-stimulated amylase release from rat
      parotid slices was studied using blockers of receptors and inhibitors of the
      intracellular messenger systems. Amylase release stimulated by histamine was
      inhibited by pyrilamine, an H1-receptor blocker, but not by cimetidine, an H2
      receptor blocker. Atropine, prazosin and yohimbine had no effect on the release.
      Histamine-stimulated amylase release was inhibited by W-7, ML-9 and H-7,
      inhibitors of a calmodulin, a myosin light chain kinase (MLCK) and protein kinase
      C, respectively, while H-8, an inhibitor of protein kinase A, did not inhibit the
      release. These results suggest that histamine stimulation evokes amylase release
      via H1-receptors, followed by the Ca2+-dependent systems involving calmodulin,
      MLCK and protein kinase C.

PMID- 7583521
TI  - Inhibition of constitutive and inducible cyclooxygenase activity in human
      platelets and mononuclear cells by NSAIDs and Cox 2 inhibitors.
AB  - A range of NSAIDs and reported Cox 2 selective compounds were tested in human
      freshly isolated platelets and LPS-stimulated mononuclear cells to determine
      their potency and selectivity as inhibitors of constitutive (presumably Cox 1)
      and inducible (presumably Cox 2) cyclooxygenase respectively. All compounds
      tested were either equipotent at inhibiting constitutive and inducible
      cyclooxygenase or were selective for the inducible form. The most selective
      compound was Dup697 and the least selective, ketoprofen. Several compounds only
      produced a partial inhibition of constitutive cyclooxygenase as the maximum
      inhibitor concentration achievable in the assay was limited to 1 mM. With the
      exception of paracetamol, all compounds were able to produce full inhibition
      curves against the inducible form. Potency estimates against constitutive Cox
      compare closely with published data but most compounds were consistently more
      potent against the inducible isoform than in published data for human cloned,
      microsomal Cox 2. These data suggest that human mononuclear cells are either
      exquisitely sensitive to some NSAIDs or they may contain another Cox isoform as
      yet indistinguishable from Cox 2.

PMID- 7583524
TI  - T2-weighted contrast for NMR characterization of human atherosclerosis.
AB  - We sought to determine whether 1H NMR images without chemical-shift selection can
      adequately characterize the components of human atheromatous arteries. NMR, as a
      nondestructive, biochemical imaging tool, has the potential to identify lipids in
      atherosclerotic plaques but has not yet produced detailed images of atheroma
      components. Using 1H NMR spectroscopy at 9.4 T, we examined microdissected
      components of diseased and normal arteries to determine water relaxation
      constants (T1 and T2) as well as the relative content of mobile lipid. Relaxation
      times were also measured at 1.5 and 4.7 T. Sections of arteries with
      atherosclerotic lesions of graded severity were imaged at 1.5 and 9.4 T. The
      contrast-to-noise ratio (CNR) was used to assess lesion conspicuity. In the
      atheromatous core, the water NMR signal predominates over that of lipid (lipid-to
      water ratio, 0.11). At 9.4 T, T2 is 20.2 ms for the atheromatous core, 30.1 ms
      for the collagenous cap, and 29.5 ms for normal media. This results in a high CNR
      on T2-weighted (T2w) images for atheromatous core compared with the collagenous
      cap and normal media. A similar contrast was measured at lower field strength.
      Calcifications do not generate appreciable signal due to their low water content
      but can be detected on T1-weighted (T1w) images. The water T2 contrast allows
      discrimination of the atheromatous lipid core from collagenous regions. The
      combination of T1w and T2w sequences permits in vitro identification of the
      atheromatous core, collagenous cap, calcifications, media, adventitia, and
      perivascular fat. The discrimination of collagen fibers that overlie lipid
      deposits permits study of plaque protection and stability at all field strengths
      and may provide the basis for in vivo microscopy of human atherosclerosis.

PMID- 7583523
TI  - Involvement of blood coagulation factor XIII in burn healing in the carbon
      tetrachloride-induced hepatic injury model in rats.
AB  - An involvement of blood coagulation factor XIII (FXIII) in healing of burns was
      examined in rats with the carbon tetrachloride (CCl4)-induced hepatic injury. The
      oral administration of 2 and 4 ml/kg CCl4 to rats every 4 days delayed healing of
      the burns induced on the back skin and decreased FXIII activity. These animals
      showed some hepatotoxic signs (increased glutamic-oxaloacetic and glutamic
      pyruvic transaminases) and accelerated blood coagulation system (increased
      fibrino-peptide A and fibrin degradation product). The delay in the burn healing
      was shortened by repeated intravenous injections with normal human placenta
      derived FXIII concentrate (Fibrogammin P; 120 U/body) every 4 days. There was a
      negative correlation between plasma FXIII activity at the end of experiment and
      the time required for wound healing. These findings suggest that reduction in
      FXIII activity may be one of the factors inducing delayed wound healing in the
      CCl4-induced hepatic injury rats.

PMID- 7583526
TI  - Association of hormone replacement therapy with hemostatic and other
      cardiovascular risk factors. The FINRISK Hemostasis Study.
AB  - The risk of cardiovascular diseases in women is small until menopause but
      increases considerably afterwards. When all age groups are considered,
      cardiovascular diseases are responsible for approximately half of the total
      mortality in women. It has been suggested that hormone replacement therapy (HRT)
      in perimenopausal and postmenopausal women could be useful in the prevention of
      cardiovascular diseases, but its effects are insufficiently known. We performed a
      cross-sectional study on the associations of menopause and HRT with
      cardiovascular risk factors, in particular with hemostatic factors, on female
      participants of the FINRISK Hemostasis Study. The participants, aged 45 to 64
      years, were recruited from the Finnish population register by random sampling
      from three geographically defined areas. The participation rate of women was
      83.2%. Of the 1202 women included in the study, 29.2% were current users of HRT.
      Differences in cardiovascular risk factors by menopausal status and by HRT use
      were examined after adjustment for age, study area, current smoking, body mass
      index, self-reported diabetes, and years of education. Postmenopausal women not
      using exogenous sex hormones had on average a total cholesterol level 0.5 mmol/L
      (8.9%) higher and an LDL cholesterol level 0.4 mmol/L (11.4%) higher than
      premenopausal women. Women reporting irregular menstruation (presumably due to
      perimenopause) had higher adjusted plasma fibrinogen, factor VII coagulant
      activity, and factor VII antigen than women with regular menstruation or no
      menstrual periods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583525
TI  - Magnetic resonance imaging-assessed adipose tissue and serum lipid and insulin
      concentrations in growth hormone-deficient adults. Effect of growth hormone
      replacement.
AB  - The visceral and subcutaneous abdominal adipose tissue (AT) areas and the
      subcutaneous hip AT area were assessed by magnetic resonance imaging (MRI) in
      relation to serum lipid and plasma insulin levels in 12 growth hormone-deficient
      (GHD) adults before and after 6 months of replacement therapy with recombinant
      human growth hormone (rhGH) and in 12 healthy control subjects. Compared with
      control subjects, GHD patients had a significantly increased amount of visceral
      AT, which was inversely related with plasma HDL cholesterol and positively
      correlated with plasma triglyceride levels. Visceral AT was not associated with
      plasma total and LDL cholesterol or plasma insulin concentrations. GHD patients
      also had elevated serum total cholesterol, LDL cholesterol, and triglyceride
      levels compared with control subjects. After 6 months of rhGH replacement therapy
      the mean visceral, subcutaneous abdominal, and subcutaneous hip AT areas and
      serum concentration of total cholesterol decreased significantly, whereas serum
      HDL cholesterol concentration increased significantly. No significant
      correlations were found between changes in the amount of AT and changes in serum
      lipid and plasma insulin levels.

PMID- 7583527
TI  - Estrogen-induced alterations in lipoprotein metabolism in autoimmune MRL/lpr
      mice.
AB  - Estrogen replacement therapy has been demonstrated to shift the lipoprotein
      profile toward a less atherogenic one with concomitant increases in HDL and
      reductions in LDL cholesterol and serum triglycerides. Estrogen, however, has
      also been implicated in playing a significant role in autoimmune disease and may
      be involved with disease incidence and progression. The MRL/lpr mouse strain
      represents an autoimmune disease model with features resembling systemic lupus
      erythematosus including high-titer autoantibodies, glomerulonephritis, and
      vasculitis. In the present study, the effects of estrogen treatment on serum
      lipoprotein profiles were investigated by fast protein liquid chromatography in
      female MRL/lpr mice, in the MRL/++ strain with a milder form of disease, and in
      control Balb/c mice. Treatment of MRL/lpr mice for periods of 1 week or longer
      with pharmacologic doses of estrogen resulted in a significant increase in the
      amount of cholesterol carried on LDL particles. The up to eightfold increase in
      LDL cholesterol was less significant in the MRL/++ or Balb/c mice. Maximal
      increases were observed at 1 to 2 mg/kg of estrogen agonists, and the effect on
      LDL cholesterol increases was inhibited by tamoxifen. The HDL-to-LDL shift in
      cholesterol observed in estrogen-treated autoimmune mice correlated with an
      increase in apolipoprotein E, primarily on larger HDL particles. In addition to
      the increase in LDL cholesterol, hormonal treatment also resulted in a shift in
      triglycerides from the VLDL to the LDL fraction in both normal and autoimmune
      mice. These results suggest that pharmacologic doses of estrogen may contribute
      to cardiovascular disease progression by shifting the relative distribution of
      cholesterol from HDL to LDL in this murine model of lupus.

PMID- 7583528
TI  - T helper cell infiltration and foam cell proliferation are early events in the
      development of atherosclerosis in cholesterol-fed rabbits.
AB  - The involvement of T cells in the early cellular events in atherosclerosis was
      studied in rabbits fed a 1% cholesterol diet by use of specific monoclonal anti
      rabbit CD5 and CD4 antibodies. T cells were not seen in the aortic intimas of
      rabbits not fed cholesterol but were seen in intimal lesions in cholesterol-fed
      rabbits. Accumulation of T cells in plaques occurred between 2 and 4 weeks after
      commencement of cholesterol feeding, and the greatest density of CD5-positive T
      cells were observed after 4 weeks (11.2 +/- 6.0 cells/mm2 [mean +/- SEM]; P < .02
      compared with normal control rabbits, P < .03 compared with 2-week plaques).
      Staining for CD4 indicated that the majority of these T cells were T helper cells
      (9.9 +/- 4.9 cells/mm2). At this time, plaques showed a dense cellular infiltrate
      of macrophages (3623 +/- 467 cells/mm2) and macrophage proliferation was evident
      (2.1 +/- 1.1% of total plaque cells). As the cross-sectional area of intimal
      lesions increased progressively in subsequent weeks, their cellularity declined
      (8 weeks, 2239 +/- 271 cells/mm2; 12 weeks, 1535 +/- 55 cells/mm2; 16 weeks, 1747
      +/- 242 cells/mm2, P < .05 for all groups compared with the 4-week group). The
      density of the T cell infiltrate (8 weeks, 6.7 +/- 3.0 cells/mm2; 12 weeks, 0.6
      +/- 0.2 cells/mm2; 16 weeks, 1.0 +/- 0.4 cells/mm2) and the proliferative index
      of cells within plaques (8 weeks, 0.6 +/- 0.2%; 12 weeks, 0.8 +/- 0.3%; 16 weeks,
      0.2 +/- 0.2%) also declined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583530
TI  - Oxidized LDL induces enhanced antibody formation and MHC class II-dependent IFN
      gamma production in lymphocytes from healthy individuals.
AB  - The early stages of atherosclerosis are characterized by penetration into the
      arterial intima by both T lymphocytes and monocytes. Some of these T lymphocytes
      show signs of activation, though the mechanisms by which they become activated
      are not known. The monocytes develop into macrophages and subsequently into foam
      cells filled with oxidized LDL (oxLDL)-derived lipids. OxLDL has been found to
      exert several proinflammatory effects, including enhanced adhesiveness of
      endothelial cells and monocytes, chemotaxis of monocytes and T cells, and T-cell
      activation. The enzyme-linked immunospot (ELISPOT) assay has been shown to be a
      sensitive method for detection of single cells secreting antibodies or cytokines.
      Here we have used this method to characterize the T-cell cytokine secretion
      pattern after exposure to oxLDL in vitro. In peripheral blood mononuclear cells
      from healthy donors (n = 27), a significantly enhanced number of INF-gamma
      producing cells was detected by ELISPOT (P < .001) after stimulation with 5
      micrograms/mL oxLDL. In contrast, production of interleukin-4 was not
      significantly enhanced after stimulation with oxLDL. OxLDL-induced IFN-gamma
      secretion and T-cell proliferation were completely inhibited by major
      histocompatibility complex (MHC) class II antibodies. Furthermore, oxLDL was
      found to enhance the antibody secretion, indicating B-cell activation. Our
      results indicate that oxLDL activates T cells by an MHC class II-dependent
      mechanism. In healthy individuals, oxLDL induces IFN-gamma, which is produced by
      T helper type 1-like cells. These findings demonstrate that oxLDL induces a cell
      dependent immune reaction, which may play an important role in the development of
      atherosclerosis.

PMID- 7583531
TI  - Oxidized LDL induces transcription factor activator protein-1 but inhibits
      activation of nuclear factor-kappa B in human vascular smooth muscle cells.
AB  - Oxidized LDL (Ox-LDL) has been implicated in the development of atherosclerotic
      lesions, mainly due to its enhanced uptake by macrophages and its ability to
      alter gene expression in arterial cells. In the present study we demonstrated
      that Ox-LDL activates activator protein-1 (AP-1), a transcription factor
      generally induced by mitogenic substances. Lysophosphatidylcholine, which is
      generated during oxidation of LDL, stimulated AP-1 in a dose-dependent manner. In
      contrast, the radical-dependent transcription factor nuclear factor-kappa B (NF
      kappa B) was not activated by Ox-LDL, and at a concentration of 50 micrograms/mL,
      Ox-LDL inhibited lipopolysaccharide-induced activation of NF-kappa B. Oxysterols
      but not lysophosphatidylcholine inhibited lipopolysaccharide-induced NF-kappa B
      activation, suggesting that they may be responsible for the inhibitory effect of
      Ox-LDL. In conclusion, Ox-LDL has opposing effects on the activities of NF-kappa
      B and AP-1, suggesting involvement of mechanisms for transcriptional regulation
      that are strongly affected by lipid oxidation products.

PMID- 7583529
TI  - Increased autoantibody titers against epitopes of oxidized LDL in LDL receptor
      deficient mice with increased atherosclerosis.
AB  - Increasing evidence indicates that immune processes modulate atherogenesis.
      Oxidized LDL (Ox-LDL) is immunogenic, and autoantibodies recognizing epitopes of
      Ox-LDL have been described in plasma and in atherosclerotic lesions of several
      species. To determine whether the titer of such autoantibodies correlates with
      the extent of atherosclerosis, we followed the development of antibodies against
      malondialdehyde-lysine, an epitope of Ox-LDL, in two groups of LDL receptor
      deficient mice for 6 months. One group was fed an atherogenic diet (21% fat and
      0.15% cholesterol) that resulted in marked hypercholesterolemia and extensive
      aortic atherosclerosis; the other group was fed regular rodent chow (4% fat) that
      did not alter plasma cholesterol levels and induced minimal atherosclerosis.
      Autoantibody titers significantly increased over time in the group on the
      atherogenic diet, whereas they remained constant in the chow-fed group. When data
      from both groups were pooled, a significant correlation was found between the
      autoantibody titers and the extent of atherosclerosis (r = .61, P < .01).
      Autoantibody titers also correlated with plasma cholesterol levels (r = .48, P <
      .05). These results suggest that the rise in autoantibody titers to an epitope of
      Ox-LDL in this murine model is partially determined by the extent of
      atherosclerosis but could also be influenced by the degree of
      hypercholesterolemia or other factors that may influence lipid peroxidation.

PMID- 7583534
TI  - Glycosphingolipid accumulation in the aortic wall is another feature of human
      atherosclerosis.
AB  - High accumulation of lipids is a typical feature of an atherosclerotic lesion. We
      have previously identified the chemical structure of the major glycosphingolipids
      (GSLs) of human aorta; however, quantification of the absolute concentration of
      GSLs was not carried out. In the present study, for the first time we have
      performed a quantitative comparative analysis of GSL composition in the media and
      two sublayers of the intima taken from normal regions, fatty streaks, and
      atherosclerotic plaques of the human aorta. The intimal tissue containing fatty
      streaks and atherosclerotic plaques accumulated GSLs, predominantly
      glucosylceramide (GlcCer), lactosylceramide (LacCer), and ganglioside GM3. GSL
      levels in plaques were highest: GlcCer was 18- and 8-fold, LacCer was 8- and 7
      fold, and GM3 was 2.5- and 12-fold higher than in musculoelastic and elastic
      hyperplastic intimal layers of normal regions, respectively. We did not observe a
      significant increase in other GSLs. An increase in the content of gangliosides
      GD3 and GD1a was detected in the media underlying atherosclerotic lesions. On the
      basis of an analysis of the ratio of GlcCer, LacCer, and GM3 accumulated in the
      tissue and cells of the elastic-hyperplastic layer of intima, we have concluded
      that the accumulation of the above-mentioned GSLs occurs mainly in the
      extracellular space of the intima. In this study, we have also demonstrated that
      extracellular lipid liposomes, which appear in the early stages of atherogenesis,
      are one locus of GSL accumulation in the extracellular space of the
      intima.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583533
TI  - Inhibition of lecithin-cholesterol acyltransferase and modification of HDL
      apolipoproteins by aldehydes.
AB  - Experimental evidence suggests that aldehydes generated as a consequence of lipid
      peroxidation may be involved in the pathogenesis of atherosclerosis. It is well
      documented that aldehydes modify LDL: however, less is known concerning the
      effects of aldehydes on other plasma and interstitial fluid components. In the
      present study, we investigated the effects of five physiologically relevant
      aldehydes (acetaldehyde, acrolein, hexanal, 4-hydroxynonenal [HNE], and
      malondialdehyde [MDA]) on two key constituents of the antiatherogenic reverse
      cholesterol transport pathway, lecithin-cholesterol acyltransferase (LCAT) and
      HDL. Human plasma was incubated for 3 hours at 37 degrees C with each one of the
      five aldehydes at concentrations ranging from 0.16 to 84 mmol/L. Dose-dependent
      decreases in LCAT activity were observed. The short-chain (acrolein) and long
      chain (HNE) alpha,beta-unsaturated aldehydes were the most effective LCAT
      inhibitors. Micromolar concentrations of these unsaturated aldehydes resulted in
      significant reductions in plasma LCAT activity. The short- and longer-chain
      saturated aldehydes acetaldehyde and hexanal and the dialdehyde MDA were
      considerably less effective at inhibiting LCAT than were acrolein and HNE. In
      addition to inhibiting LCAT, aldehydes increased HDL electrophoretic mobility and
      cross-linked HDL apolipoproteins. Cross-linking of apolipoproteins A-I and A-II
      required higher aldehyde concentrations than inhibition of LCAT. The alpha,beta
      unsaturated aldehydes acrolein and HNE were fourfold to eightfold more effective
      cross-linkers of apolipoproteins A-I and A-II than the other aldehydes studied.
      These data suggest that products of lipid peroxidation, especially unsaturated
      aldehydes, may interfere with normal HDL cholesterol transport by inhibiting LCAT
      and modifying HDL apolipoproteins.

PMID- 7583535
TI  - Human atherosclerotic plaque contains both oxidized lipids and relatively large
      amounts of alpha-tocopherol and ascorbate.
AB  - We assessed the antioxidant status and contents of unoxidized and oxidized lipids
      in freshly obtained, homogenized samples of both normal human iliac arteries and
      carotid and femoral atherosclerotic plaque. Optimal sample preparation involved
      homogenization of human atherosclerotic plaque for 5 minutes, which resulted in
      recovery of most of the unoxidized and oxidized lipids without substantial
      destruction of endogenous vitamins C and E and 87% and 43% recoveries of added
      standards of alpha-tocotrienol and isoascorbate, respectively. The total protein,
      lipid, and antioxidant levels obtained from human plaque varied among donors,
      although the reproducibility of replicates from a single sample was within 3%,
      except for ubiquinone-10 and ascorbate, which varied by 20% and 25%,
      respectively. Plaque samples contained significantly more ascorbate and urate
      than control arteries, with no discernible difference in the vitamin C redox
      status between plaque and control materials. The concentrations of alpha
      tocopherol and ubiquinone-10 were comparable in plaque samples and control
      arteries. However, approximately 9 mol percent of plaque alpha-tocopherol was
      present as alpha-tocopherylquinone, whereas this oxidation product of vitamin E
      was not detectable in control arteries. Coenzyme Q10 in plaque and control
      arteries was only detected in the oxidized form ubiquinone-10, although coenzyme
      Q10 oxidation may have occurred during processing. The most abundant of all
      studied lipids in plaque samples was free cholesterol, followed by cholesteryl
      oleate and cholesteryl linoleate (Ch18:2). Approximately 30% of plaque Ch18:2 was
      oxidized, with 17%, 12%, and 1% present as fatty acyl hydroxides, ketones, and
      hydroperoxides, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583532
TI  - Transcriptional activation of the macrophage-colony stimulating factor gene by
      minimally modified LDL. Involvement of nuclear factor-kappa B.
AB  - Minimally modified LDL (MM-LDL), obtained by mild iron oxidation or prolonged
      storage at 4 degrees C, has been shown to induce the expression of macrophage
      colony stimulating factor (M-CSF) in cultured aortic endothelial cells. To
      examine whether other cell types also respond to MM-LDL, we investigated its
      effect on the expression of M-CSF mRNA in mouse L-cells and human aortic smooth
      muscle cells. Both L-cells and human aortic smooth muscle cells showed increased
      levels of M-CSF mRNA in response to 10 to 200 micrograms/mL MM-LDL in a dose
      dependent manner. This allowed us to use mouse L-cells as a model to study the
      mechanism involved in MM-LDL-mediated increase in M-CSF mRNA. Nuclear runon
      assays showed that M-CSF gene transcription was activated by MM-LDL. In the
      present study, we identified specific elements that conferred MM-LDL-mediated
      transcriptional activation of the human M-CSF gene. Chimeric constructs
      containing sequential deletions in the 5'-promoter region of the M-CSF gene
      linked to a reporter chloramphenicol acetyltransferase (CAT) gene were
      transfected into mouse L-cells. The human M-CSF promoter region extending
      upstream from the transcription start site to nucleotide -406 showed maximum
      induction of CAT activity by MM-LDL. Induction of CAT activity was drastically
      reduced, with a deletion plasmid lacking the promoter region -406 to -344. A
      functional nuclear factor (NF)-kappa B binding site present in this critical
      region was required for MM-LDL-mediated induction of CAT activity since an
      internal deletion construct lacking this element showed significant loss of
      transcriptional activation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583536
TI  - Effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) on
      atherosclerosis in apoE-deficient mice.
AB  - Apolipoprotein (apo) E-deficient mice develop atherosclerotic lesions that
      contain epitopes formed during the oxidative modification of lipoproteins, and
      they demonstrate high titers of circulating autoantibodies against such epitopes,
      suggesting that this murine strain may provide a model to investigate the
      atherogenic mechanisms of oxidized lipoproteins (Palinski et al, Arterioscler
      Thromb. 1994; 14:605-616). To test the hypothesis that lipoprotein oxidation
      contributes to lesion formation in apoE-deficient mice, we studied the effect of
      the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) in mice fed a high-fat
      diet containing 0.15% cholesterol. Animals were divided into two subgroups
      matched for sex and plasma cholesterol levels, and DPPD (0.5% wt/wt) was added to
      the diet of one subgroup. Throughout the 6 months of intervention, DPPD treatment
      had no significant effect on plasma cholesterol. Plasma levels of DPPD at the end
      of the experiment were 33.1 mumol/L. As judged by resistance to loss of
      polyunsaturated fatty acids, lipoproteins (d < 1.019 g/mL) from DPPD-treated
      animals showed greater resistance to copper-induced oxidation than lipoproteins
      from control animals. In addition, there was a greater than twofold prolongation
      of the lag time in the formation of conjugated dienes in the LDL and IDL
      fractions of DPPD-treated mice. Atherosclerosis was significantly reduced, by 36%
      in the DPPD-treated mice (14.0 +/- 4.53% of aortic surface area versus 21.9 +/-
      11.6%; n = 32; P < .02). These results are consistent with the hypothesis that
      lipoprotein oxidation contributes to atherogenesis in apoE-deficient mice.
      However, further studies with other antioxidants are needed to validate this
      hypothesis.

PMID- 7583539
TI  - Angiotensin II increases cGMP content via endothelial angiotensin II AT1 subtype
      receptors in the rat carotid artery.
AB  - Angiotensin II (Ang II) has been reported to modulate cGMP formation in various
      types of cells. To acquire direct information on the intracellular transduction
      involved in this mechanism, we tested the effects of Ang II on vascular tone and
      on cGMP content of in vitro isolated carotid arteries from 12-week-old Wistar
      Kyoto rats. Segments of carotid artery 20 mm long (n = 8 for each group)
      maintained at a transmural pressure of 100 mm Hg were immersed in a bath (38
      degrees C) containing oxygenated Tyrode's solution. At the end of each
      experiment, the vessel diameter was measured, and the wall cGMP content was
      determined by enzyme immunoassay. Under basal conditions, mean diameter was 968
      +/- 19 microns, and mean cGMP carotid artery content was 38.9 +/- 3.5 fmol/mg
      tissue. Incubation for 20 minutes with Ang II (10(-5) mol/L) significantly
      increased cGMP wall content, twofold above the basal content (P < .01), and
      constricted the vessel (60 +/- 2.2% of the control diameter, P < .001). After
      preincubation with a nonselective antagonist of Ang II receptors, saralasin
      ([Sar1,Val5,Ala8]Ang II, 5 x 10(-5) mol/L), or with a specific antagonist of Ang
      II AT1 receptor subtype, losartan (5 x 10(-5) mol/L), carotid diameter and cGMP
      content were no longer affected by Ang II. Exposure of carotid arteries to a
      specific antagonist of Ang II AT2 receptor, PD 123319 (10(-7) mol/L), modified
      neither Ang II-induced diameter decrease nor cGMP content increase. Constriction
      of the vessel with KCl (26 +/- 3%, P < .001) did not modify the basal cGMP wall
      content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583537
TI  - Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman
      primate by probucol. II. Cellular composition and proliferation.
AB  - In nonhuman primates (Macaca nemestrina) treated with the antioxidant probucol
      during diet-induced hypercholesterolemia, intimal lesion area in the thoracic
      aorta was decreased, with increased resistance of plasma LDL to oxidation. The
      cellular and molecular changes associated with the decrease in lesion size in the
      probucol-treated hypercholesterolemic animals are quantitatively evaluated in
      this study. Lesions from the probucol-treated animals appear less mature and have
      altered lipid distribution. Abundant lipid-laden smooth muscle cells are found in
      the intima and media of the probucol-treated animals, with fewer medial lipid
      laden macrophages, compared with lesions at similar sites in the control
      hypercholesterolemic animals. In both the control and probucol-treated animals,
      macrophages are the predominant cells in most lesions, but the ratio of
      macrophages to smooth muscle cells is decreased in the lower thoracic and upper
      abdominal aortic sites in the probucol-treated animals. Lesions at all aortic
      sites in the probucol-treated animals have a 35% to 80% reduction in the
      percentage of cells in cell cycle traverse, as indicated by immunostaining for
      proliferating cell nuclear antigen (% PCNA-positive). In both groups, macrophages
      and smooth muscle cells are PCNA-positive, but the majority (> 60%) are
      macrophages. No difference in % PCNA-positive cells is seen in the iliac
      arteries, where the most advanced lesions were present at the time probucol
      administration was initiated. Limited Northern analysis of growth-regulatory
      molecules possibly involved in the cellular changes associated with lesions shows
      a 30% to 50% decrease in mRNA levels of platelet-derived growth factor (PDGF) B
      chain, PDGF beta-receptor, colony-stimulating factor type 1, and monocyte
      chemotactic protein 1. Thus, a potential role for an antioxidant such as probucol
      in the treatment of atherosclerosis may be to alter the early inflammatory
      fibroproliferative processes of the disease. Whether these effects are directly
      related to the antioxidant properties or some other activity of probucol is not
      yet known.

PMID- 7583540
TI  - Nitric oxide protects against leukocyte-endothelium interactions in the early
      stages of hypercholesterolemia.
AB  - We studied the effects of CAS1609, a nitric oxide donor, on leukocyte-endothelial
      interactions during the early stages of hypercholesterolemia in rat mesenteric
      microcirculation. Rats were randomly divided into four groups: (a) rats fed
      control diet, (b) rats fed control diet while receiving CAS1609, (c) rats fed a
      high-cholesterol (HC) diet and given C93-4845 (an inactive control compound), and
      (d) rats fed an HC diet and given CAS1609. Both HC groups developed significantly
      elevated plasma cholesterol levels compared with rats fed the control diet.
      Intravital microscopy of mesenteric venules revealed a significant increase in
      leukocyte rolling and adherence in the untreated HC rats compared with control
      rats (P < .01). This was significantly attenuated in the HC rats given CAS1609.
      The HC rats given C93-4845 also developed aortic endothelial dysfunction (ie,
      impaired relaxation to acetylcholine or ADP) that was significantly prevented by
      CAS1609 infusion (P < .02). Immunohistochemical staining of ileum demonstrated
      significantly enhanced localization of P-selectin and intercellular adhesion
      molecule-1 (ICAM-1) on venular endothelium in the untreated HC rats compared with
      control rats (P < .01). However, P-selectin and ICAM-1 expression were
      significantly attenuated in HC rats given CAS1609 (P < .05 and P < .01,
      respectively). Thus, hypercholesterolemia induces microvascular dysfunction
      characterized by loss of endothelium-derived nitric oxide, increased rolling and
      adherence of leukocytes, and increased expression of P-selectin and ICAM-1.
      Infusion of CAS1609 significantly attenuated these changes due to
      hypercholesterolemia. Our data suggest that nitric oxide plays a significant role
      in the prevention of the early endothelial dysfunction observed in
      hypercholesterolemia.

PMID- 7583538
TI  - Relaxation of the carotid artery to hypoxia is impaired in Watanabe heritable
      hyperlipidemic rabbits.
AB  - We tested the hypothesis that relaxation of the carotid artery during hypoxia is
      mediated by activation of glibenclamide-sensitive potassium channels and that
      this response is impaired in hyperlipidemic rabbits. In New Zealand White rabbits
      (plasma cholesterol, 69 +/- 12 mg/dL, mean +/- SEM) and Watanabe heritable
      hyperlipidemic (WHHL) rabbits (plasma cholesterol, 677 +/- 99 mg/dL), tension of
      the carotid artery was measured in an organ bath under control conditions and
      during two levels of hypoxia. In normal rabbits, mild hypoxia produced 21 +/- 2%
      relaxation in arteries precontracted with phenylephrine. Removal of endothelium
      or the nitric oxide synthase inhibitor NG-nitro-L-arginine (10(-4) mol/L) almost
      abolished relaxation in response to mild hypoxia in normal rabbits. Glibenclamide
      (10(-6) mol/L), an inhibitor of ATP-sensitive potassium channels, attenuated
      relaxation during mild hypoxia by almost 60%. In WHHL rabbits mild hypoxia
      relaxed the carotid artery by only 9 +/- 4% (P < .05 versus normal rabbits).
      Severe hypoxia produced greater relaxation of the carotid artery in normal than
      in WHHL rabbits (85 +/- 5% versus 52 +/- 8%, respectively, P < .05).
      Glibenclamide but not endothelial denudation or NG-nitro-L-arginine attenuated
      relaxation during severe hypoxia in normal and WHHL rabbits. Relaxation of the
      carotid artery to sodium nitroprusside was similar in normal and WHHL rabbits.
      These findings suggest that relaxation of the carotid artery in response to mild
      and severe hypoxia is impaired in WHHL rabbits and is mediated, in large part, by
      activation of glibenclamide-sensitive potassium channels.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7583541
TI  - Retinoids stimulate fibrinogen production both in vitro (hepatocytes) and in
      vivo. Induction requires activation of the retinoid X receptor.
AB  - The in vitro effects of retinoids on fibrinogen synthesis were investigated in
      HepG2 cells and primary human hepatocytes. In vivo effects were studied in the
      rat. In HepG2 cells, maximal stimulation (twofold) of fibrinogen secretion was
      obtained when cells were incubated in the presence of 1 mumol/L all-trans
      retinoic acid (T-RA) for 24 hours. A comparable increase was observed for both de
      novo fibrinogen synthesis and fibrinogen beta chain mRNA level. In primary
      cultures of human hepatocytes, treatment with 1 mumol/L T-RA for 72 hours also
      gave a twofold increase in fibrinogen production. Furthermore, rats treated for 6
      days with 100 mg.kg-1.d-1 T-RA presented increased fibrinogen plasma levels
      (110%). A selective retinoic X receptor (RXR) agonist, 4-[1-3,5,5,8,8-pentamethyl
      5,6,7,8-tetrahydro-2-naphthyl)-ethenyl]benzoi c acid (3-methyl TTNEB), as well as
      9-cis retinoic acid, a natural RXR ligand, mimicked the effects of T-RA on
      fibrinogen synthesis in vitro at lower concentrations. In contrast, a selective
      retinoic A receptor alpha (RAR alpha) agonist was a poor activator. The ED50 of
      the different retinoids on fibrinogen secretion by HepG2 cells was 25 nmol/L for
      T-RA, 4 nmol/L for 9-cis retinoic acid, 11 nmol/L for the synthetic RXR agonist,
      and > 500 nmol/L for the RAR alpha agonist. However, incubation of HepG2 cells
      with RXR agonist together with RAR alpha agonist resulted in a further increase
      in fibrinogen production. The secretion of two other acute-phase proteins, alpha
      antichymotrypsin and caeruloplasmin, was also stimulated by retinoids in HepG2
      cells but by a different regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583542
TI  - Effects of exercise training and deconditioning on platelet function in men.
AB  - Platelets play an important role in the pathogenesis of cardiovascular disease.
      It has also been noticed that regular exercise can reduce the risk of
      cardiovascular disease. This is the first study to demonstrate that endurance
      exercise training may suppress platelet adhesiveness and aggregation and that
      deconditioning may reverse the training effects. Healthy male sedentary subjects
      were randomly divided into control and training groups. The trained men were
      trained on a bicycle ergometer at about 60% of maximal oxygen consumption for 30
      minutes per day, 5 days per week for 8 weeks, then deconditioned for 12 weeks.
      During the experimental period, blood samples of the trained subjects were
      collected before and immediately after a progressive exercise test every 4 weeks.
      The same experiments were applied to the controls at the beginning of this study
      and 8 weeks thereafter. A tapered parallel-plate chamber was used to assess
      platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the
      percentage of reduction in single platelet count. Our results showed that (1)
      platelet adhesiveness and aggregability were increased by short-term strenuous
      exercise in both control and trained groups, but the enhancement of platelet
      aggregability was decreased after exercise training in the trained subjects; (2)
      at rest and immediately after strenuous exercise, platelet adhesiveness and
      aggregability were decreased by training, whereas they were unchanged in the
      control group; and (3) deconditioning reversed the training effects on resting
      and postexercise platelet adhesiveness and aggregability back to the pretraining
      state. These results suggest that platelet adhesiveness and aggregability may be
      depressed by exercise training but be reversed back to the pretraining state
      after deconditioning.

PMID- 7583543
TI  - Heightened thrombin formation but normal plasma levels of activated factor VII in
      patients with acute coronary syndromes.
AB  - Plaque rupture with the exposure of a tissue factor-rich procoagulant surface is
      considered the common pathogenetic mechanism of unstable angina and myocardial
      infarction. Activated factor VII, the key enzyme for initiating blood coagulation
      under resting conditions, is increased in pathological situations associated with
      tissue factor exposure. We measured the plasma levels of activated factor VII and
      studied their relation with signs of coagulation enzyme activity in patients with
      acute coronary syndromes. The plasma levels of activated factor VII, prothrombin
      fragment 1 + 2, and fibrinopeptide A were measured on admission in consecutive
      patients presenting with acute myocardial infarction (n = 28), unstable angina (n
      = 32), and stable angina (n = 17) and in age- and sex-matched healthy individuals
      (n = 33). Plasma determinations of the same markers were also repeated at 15 days
      and 3 and 6 months. On admission, the patients with unstable angina or myocardial
      infarction had significantly higher plasma levels of prothrombin fragment 1 + 2
      (P < .0001) and fibrinopeptide A (P < .0001) than those with stable angina or
      healthy individuals, whereas no differences were detected in the plasma levels of
      activated factor VII. During follow-up there was a significant decrease in the
      plasma levels of fibrinopeptide A both in patients with unstable angina (P <
      .001) and in those with myocardial infarction (P < .001), whereas no changes in
      plasma prothrombin fragment 1 + 2 or activated factor VII levels were observed.
      Hence, in the acute and chronic phases of myocardial infarction and unstable
      angina, heightened coagulation enzyme activity is not accompanied by an increase
      in activated factor VII.

PMID- 7583544
TI  - Increased mitogenic response to heparin-binding epidermal growth factor-like
      growth factor in vascular smooth muscle cells of diabetic rats.
AB  - We investigated the mitogenic effects of heparin-binding epidermal growth factor
      like growth factor (HB-EGF) in vascular smooth muscle cells (SMCs) obtained from
      rats with streptozotocin (STZ)-induced diabetes and evaluated the role of heparan
      sulfate proteoglycan (HSPG) in inducing these effects. HB-EGF significantly
      increased DNA synthesis in the SMCs of diabetic rats (STZ-SMCs) compared with
      control rats (control SMCs). However, the mitogenic effects of EGF, which shares
      EGF receptors with HB-EGF, and basic fibroblast growth factor, another heparin
      binding growth factor, were similar in STZ-SMCs and control SMCs. The mitogenic
      response to HB-EGF in SMCs of insulin-treated diabetic rats was similar to the
      response in control SMCs. HB-EGF-induced autophosphorylation of EGF receptors was
      increased in STZ-SMCs compared with control SMCs, although the number of EGF
      receptors in STZ-SMCs was 40% of that in controls. This increased mitogenic
      response to HB-EGF in STZ-SMCs was completely inhibited by treatment with
      heparitinase, chlorate, and a synthetic peptide corresponding to the heparin
      binding domain of HB-EGF. Compared with heparan sulfate isolated from control
      SMCs, heparan sulfate isolated from STZ-SMCs was of smaller molecular size and
      caused a greater mitogenic effect of HB-EGF. These findings suggest that the
      mitogenic response to HB-EGF is increased in SMCs of diabetic rats. Changes in
      cell-associated heparan sulfate in STZ-SMCs may be related to the increased
      mitogenic response to HB-EGF.

PMID- 7583547
TI  - Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol
      levels in individuals heterozygous for familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is characterized by elevated plasma
      concentrations of LDL cholesterol resulting from mutations in the gene for the
      LDL receptor. Low HDL cholesterol levels are seen frequently in patients both
      heterozygous and homozygous for mutations in this gene. Suggested mechanisms for
      reduced HDL levels in FH patients have been altered apolipoprotein A-1 metabolism
      and elevated cholesteryl ester transfer protein activity, but the molecular basis
      for hypoalphalipoproteinemia in any of these patients has not yet been
      identified. We investigated four large families in which individuals were found
      to be double heterozygotes for both FH and lipoprotein lipase (LPL) deficiency.
      These double heterozygotes have significantly less HDL cholesterol than persons
      with FH or LPL heterozygosity alone. In the double heterozygotes, HDL particle
      composition is not significantly different from FH heterozygotes, suggesting a
      quantitative rather than qualitative defect in HDL metabolism in these persons.
      We propose that mutations in the LPL gene may be a cause of low HDL cholesterol
      levels in some individuals heterozygous for FH.

PMID- 7583545
TI  - Overexpression of human lipoprotein lipase protects diabetic transgenic mice from
      diabetic hypertriglyceridemia and hypercholesterolemia.
AB  - We investigated the role of the overexpression of lipoprotein lipase (LPL) in
      lipoprotein abnormalities in transgenic mice with streptozotocin-induced diabetes
      mellitus. Before the induction of diabetes, LPL activity was 4.6-fold in skeletal
      muscle and 2.0-fold higher in the heart in transgenic mice than in their
      nontransgenic littermates. LPL activity in skeletal muscles in diabetic
      nontransgenic mice and cardiac LPL activity in diabetic nontransgenic and
      transgenic mice were decreased. Body weights were similarly reduced, and no
      appreciable amount of adipose tissue was observed in diabetes in both groups. The
      plasma triglyceride level was lower in diabetic transgenic mice than in diabetic
      nontransgenic mice (33.2 +/- 22.5 versus 185.3 +/- 57.4 mg/dL). Induction of
      diabetes was associated with a significant increase in the plasma cholesterol
      level in nontransgenic mice (90.0 +/- 11.1 versus 163.9 +/- 39.3 mg/dL) but much
      less in transgenic mice. Our results indicate that overexpression of LPL in
      transgenic mice inhibited diabetes-associated hypertriglyceridemia and
      hypercholesterolemia but did not affect the loss of body weight induced by
      diabetes.

PMID- 7583548
TI  - Common mutations in the low-density-lipoprotein-receptor gene causing familial
      hypercholesterolemia in the Japanese population.
AB  - Familial hypercholesterolemia (FH) is a common genetic disorder caused by
      mutations of the LDL-receptor gene. In the present study, we investigated four
      Japanese FH homozygotes and identified five point mutations: a splice site
      mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon
      7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a
      missense mutation in exon 14 (the P664L mutation), and a missense mutation in
      exon 4 (the E119K mutation). We developed simple methods for detecting these
      mutations. When we examined the presence of these mutations in 24 unrelated FH
      homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other
      four mutations were unique for each proband. We also screened 120 unrelated FH
      heterozygotes for these mutations and found that the frequencies of the 1845 + 2
      T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7%
      (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These
      mutations were found in more than 30% of unrelated Japanese FH patients. By using
      the detection methods developed in this study, the diagnosis of more than 30% of
      the genetic bases of Japanese FH heterozygotes is expected.

PMID- 7583546
TI  - Patients with apoE3 deficiency (E2/2, E3/2, and E4/2) who manifest with
      hyperlipidemia have increased frequency of an Asn 291-->Ser mutation in the human
      LPL gene.
AB  - Approximately 1% to 2% of persons in the general population are homozygous for a
      lipoprotein receptor-binding defective form of apoE (apoE2/2). However, only a
      small percentage (2% to 5%) of all apoE2/2 homozygotes develop type III
      hyperlipoproteinemia. Interaction with other genetic and environmental factors
      are required for the expression of this lipid abnormality. We sought to
      investigate the possible role of LPL gene mutations in the development of
      hyperlipoproteinemia in apoE2/2 homozygotes and in apoE2 heterozygotes. As a
      first step, we performed DNA sequence analysis of all 10 LPL coding exons in 2
      patients with the apoE2/2 genotype who had type III hyperlipoproteinemia and
      identified a single missense mutation (Asn 291-->Ser) in exon 6 of the LPL gene.
      The mutation was then found in 5 of 18 patients with type III
      hyperlipoproteinemia who had the apoE2/2 genotype (allele frequency = 13.9%; P <
      or = 7.4 x 10(-5)) and 6 of 22 hyperlipidemic E2 heterozygous patients with the
      apoE3/2 and E4/2 genotype (allele frequency = 13.6%; P = 2.2 x 10(-5)). In
      contrast, this mutation was found in only 3 of 230 normolipidemic controls
      (allele frequency = 0.7%). In vitro mutagenesis studies revealed that the Asn 291
      ->Ser mutant LPL had approximately 60% of LPL catalytic activity and
      approximately 70% of specific activity compared with wild-type LPL. The heparin
      binding affinity of the mutant LPL was not impaired. Our data suggest that the
      Asn 291-->Ser substitution is likely to be a significant predisposing factor
      contributing to the expression of different forms of hyperlipidemia when
      associated with other genetic factors such as the presence of apoE2.

PMID- 7583549
TI  - Differences in the phenotypic characteristics of subjects with familial defective
      apolipoprotein B-100 and familial hypercholesterolemia.
AB  - Familial defective apolipoprotein B-100 (FDB) is a recently identified autosomal
      dominantly inherited disorder caused by a point mutation in the apolipoprotein
      (apo) B gene. To determine whether the phenotypic characteristics in FDB subjects
      are similar to those in subjects with familial hypercholesterolemia (FH), 76
      kindreds fulfilling the clinical criteria for heterozygous FH/FDB were
      characterized using molecular biological techniques. Allele-specific polymerase
      chain reaction (PCR) at the apoB locus was used for diagnosis or exclusion of
      FDB. PCR-based methods for detection of two point mutations (V408M and P664L) at
      the LDL receptor (LDLR) locus, cosegregation analysis using eight restriction
      fragment length polymorphisms (RFLPs) at the LDLR locus, or the exclusion of FDB
      confirmed the clinical diagnosis of FH. Three kindreds were not included because
      of a missing cosegregation between a particular haplotype and the FH phenotype.
      We predicted that a similar number of kindreds would be detected in the two
      groups, assuming comparable prevalences of the diseases in our population and
      similar phenotypic characteristics. However, only nine kindreds were identified
      with the FDB mutation compared with 64 kindreds with FH (P < .0001). From these
      73 kindreds, 28 FDB heterozygotes and 129 FH heterozygotes were compared using
      multivariate analysis. There were no differences between these two groups with
      respect to age, sex, and apoE genotype distribution, lipoprotein(a)
      concentrations, body mass index, blood pressure, and smoking habits. However, FDB
      subjects demonstrated significantly lower concentrations of total cholesterol
      (8.1 versus 10.2 mmol/L, P < .001), LDL cholesterol (6.3 versus 8.2 mmol/L, P <
      .001), and triglycerides (1.3 versus 1.8 mmol/L, P = .025) and higher
      concentrations of HDL cholesterol (1.4 versus 1.2 mmol/L, P = .015) than subjects
      with FH. In contrast to FH, female FDB subjects tended to have higher
      concentrations of total cholesterol (8.9 versus 7.5 mmol/L, P = .032) and LDL
      cholesterol (7.1 versus 5.7 mmol/L, P = .026) than FDB males. The same results
      regarding total and LDL cholesterol and sex differences were observed when
      individual data of 238 FDB and 415 FH subjects from the literature were compared.
      In addition, FDB subjects showed much larger total cholesterol fluctuations than
      FH subjects (median of intraindividual coefficients of variation: FDB, 14.5%; FH,
      5.3%; P < .001). In summary, these results demonstrate that FDB subjects tend to
      have a milder form of hyperlipoproteinemia than FH subjects and that only a part
      of the subjects with FDB fulfill the established criteria for identifying FH.

PMID- 7583550
TI  - A major locus influencing plasma high-density lipoprotein cholesterol levels in
      the San Antonio Family Heart Study. Segregation and linkage analyses.
AB  - To detect and measure the effects of a single locus on quantitative variation in
      plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical
      genetic analyses on data from 526 Mexican American individuals in 25 randomly
      ascertained pedigrees. By using maximum-likelihood complex segregation analysis,
      we found evidence for a major locus with a codominant mixture model that included
      the phenotypic means, standard deviations, relative frequency of a low HDL-C
      allele, and heritability for plasma HDL-C levels, plus the effects of sex
      (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of
      apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex
      hormone use, and menopausal status under an unrestricted general model. Inclusion
      of the four covariates (in addition to the sex and age-by-sex effects) accounted
      for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21%
      of the variance, the detected major locus accounted for approximately 55% in men
      and 21% in women; the total genetic contributions to the variance by genes were
      approximately 82% in men and 69% in women. Linkage analyses with penetrance
      parameter estimates from the segregation analysis excluded tight linkage between
      the detected major locus and markers for the following candidate loci: the
      apoAI/apoCIII genomic region (P < .05), apoB (P < .01), hepatic lipase (P <
      .001), lipoprotein lipase (P < .001), and the LDL receptor (P < .001). While not
      excluding the apoE locus (LOD = -0.348, P < .21), the analysis provided no
      support for tight linkage between it and the detected major locus.

PMID- 7583552
TI  - Generation of pre-beta 1-HDL and conversion into alpha-HDL. Evidence for
      disturbed HDL conversion in Tangier disease.
AB  - HDL encompasses several apoA-I-containing particles that differ by size and show
      pre-beta- or alpha-mobility on agarose gel electrophoresis: pre-beta 1-LpA-I, pre
      beta 2-LpA-I, pre-beta 3-LpA-I, alpha-LpA-I2, and alpha-LpA-I3. The
      quantitatively minor subclass pre-beta 1-LpA-I serves as an initial acceptor of
      cell-derived cholesterol. In this study, we generated a pre-beta 1-LpA-I-like
      particle in vitro by the incubation of biotinylated apoA-I with cholesterol
      loaded macrophages. Both native pre-beta 1-LpA-I and in vitro-generated pre-beta
      1-LpA-I were indistinguishable from lipid-free apoA-I by two-dimensional
      nondenaturing polyacrylamide gradient gel electrophoresis but exhibited a
      different size upon gel filtration. In vitro-generated biotin-pre-beta 1-LpA-I
      took up twofold to threefold more [3H]cholesterol from labeled fibroblasts during
      a 1-minute pulse incubation than lipid-free apoA-I. The in vitro conversion of
      biotin-pre-beta 1- LpA-I was investigated in the presence of plasmas of healthy
      probands and patients with Tangier disease, with apoA-I deficiency, and with
      lecithin-cholesterol acyltransferase (LCAT) deficiency. Incubation of biotin-pre
      beta 1-LpA-I with plasmas either from normoalphalipoproteinemic probands or from
      a patient with apoA-I deficiency generated a biotinylated particle with the size
      and electrophoretic mobility of alpha-LpA-I2. This conversion was sensitive to
      heating at 56 degrees C but not to the removal of calcium. Inhibition of LCAT by
      dithiobisnitrobenzoic acid led to the formation of alpha-LpA-I3 instead of alpha
      LpA-I2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583551
TI  - G-->A substitution at position -75 of the apolipoprotein A-I gene promoter.
      Evidence against a direct effect on HDL cholesterol levels.
AB  - The present study sought to resolve the contradictory evidence as to whether the
      G-->A substitution at position -75 of the apoA-I gene promoter raises HDL
      cholesterol (HDL-C) levels by examining the effect of this polymorphism in French
      Canadians, a relatively genetically homogeneous population. Among 308 women,
      carriers of the A allele displayed 12% and 10% higher mean plasma HDL-C and apoA
      I concentrations, respectively, than did noncarriers. Among 345 men, no effect of
      the A allele was noted. The frequency distribution of HDL-C levels in women
      carrying the A but not the G allele appeared bimodal, with one peak corresponding
      to the mean of the noncarriers and a second to higher HDL-C. Thus it appears that
      only a subset of A alleles confers high HDL-C levels. This hypothesis was
      supported by data from four kindreds within which some but not all A alleles
      segregated with hyperalphalipoproteinemia. The data suggest that the A
      substitution in the apoA-I gene promoter does not directly confer high HDL-C
      levels but may be in linkage disequilibrium with other sequence polymorphism(s)
      at this locus in a subset of alleles that raise HDL-C levels.

PMID- 7583553
TI  - Lipoproteins containing apolipoprotein A-IV but not apolipoprotein A-I take up
      and esterify cell-derived cholesterol in plasma.
AB  - Two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D
      PAGGE) identifies distinct apoA-I-or apoE-containing subclasses of high-density
      lipoproteins (HDLs), each of which plays a different role in reverse cholesterol
      transport. In this study we used 2D-PAGGE to investigate the role of apoA-IV
      containing lipoproteins in reverse cholesterol transport in native plasma.
      Incubation of 2D electrophoretograms with anti-apoA-IV antibodies identified up
      to three subclasses of particles. The smaller particle subclasses, LpA-IV-1 and
      LpA-IV-2, were found in every plasma sample. The largest particle subclass, LpA
      IV-3, was observed in fewer than 10% of the plasmas analyzed. 2D-PAGGE of apoA-I
      deficient plasma and apoA-I-depleted plasma and anti-apoA-I immunosubtracting 2D
      PAGGE of normal plasma revealed that LpA-IV-1 and LpA-IV-2 do not contain apoA-I.
      The importance of LpA-IV-1 and LpA-IV-2 for uptake and esterification of cell
      derived cholesterol was investigated using pulse-chase incubations of plasma with
      [3H]cholesterol-labeled fibroblasts followed by anti-apoA-I immunosubtracting 2D
      PAGGE. During 1-minute pulse incubation with cells, [3H]cholesterol was taken up
      by gamma-LpE > LpA-IV-1 > pre-beta 1-LpA-I > LpA-IV-2 (">" denotes "more than").
      During subsequent chase incubation without cells, proportionately less
      radioactivity disappeared from LpA-IV-1 and LpA-IV-2 than from pre-beta 1-LpA-I
      and gamma-LpE. During 5-minute pulse incubations, radioactive cholesteryl esters
      were formed in pre-beta 3-LpA-I > alpha-LpA-I > LpA-IV-1 > LpA-IV-2. The
      fractional estertification rate was highest in pre-beta 2-LpA-I and lowest in
      alpha-LpA-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583554
TI  - PAF-degrading acetylhydrolase is preferentially associated with dense LDL and
      VHDL-1 in human plasma. Catalytic characteristics and relation to the monocyte
      derived enzyme.
AB  - In human plasma, platelet activating factor (PAF)-degrading acetylhydrolase
      (acetylhydrolase) is principally transported in association with LDLs and HDLs;
      this enzyme hydrolyzes PAF and short-chain forms of oxidized phosphatidylcholine,
      transforming them into lyso-PAF and lysophosphatidylcholine, respectively. We
      have examined the distribution, catalytic characteristics, and transfer of
      acetylhydrolase activity among plasma lipoprotein subspecies separated by
      isopycnic density gradient ultracentrifugation; the possibility that the plasma
      enzyme may be partially derived from adherent monocytes has also been evaluated.
      In normolipidemic subjects with Lp(a) levels < 0.1 mg/mL, acetylhydrolase was
      associated preferentially with small, dense LDL particles (LDL-5; d = 1.050 to
      1.063 g/mL) and with the very-high-density lipoprotein-1 subfraction (VHDL-1; d =
      1.156 to 1.179 g/mL), representing 23.9 +/- 1.7% and 20.6 +/- 3.2%, respectively,
      of total plasma activity. The apparent Km values for PAF of the enzyme associated
      with such lipoproteins were 89.7 +/- 23.4 and 34.8 +/- 4.5 mumol/L for LDL-5 and
      VHDL-1, respectively: indeed, the Km value for LDL-5 was some 10-fold higher than
      that of the light LDL-1, LDL-2, and LDL-3 subspecies, whereas the Km of VHDL-1
      was some twofold greater than those of the HDL-2 and HDL-3 subspecies.
      Furthermore, when expressed on the basis of unit plasma volume, the Vmax of the
      acetylhydrolase associated with LDL-5 was some 150-fold greater than that in LDL
      1 (d = 1.019 to 1.023 g/mL). No significant differences in the pH dependence of
      enzyme activity or in sensitivity to protease inactivation, sulfydryl reagents,
      the serine protease inhibitor Pefabloc, or the PAF antagonist CV 3988 could be
      detected between apo B-containing and apo A-I-containing lipoprotein particle
      subspecies. Incubation of LDL-1 (Km = 8.4 +/- 2.6 mumol/L) and LDL-2 (d = 1.023
      to 1.029 g/mL; Km = 8.4 +/- 3.3 mumol/L) subspecies with LDL-5, in which
      acetylhydrolase had been inactivated by pretreatment with Pefabloc, demonstrated
      preferential transfer of acetylhydrolase to LDL-5. Acetylhydrolase transferred to
      LDL-5 from the light LDL subspecies exhibited a Km of 9.4 +/- 2.2 mumol/L, a
      value characteristic of the particle donors. Finally, acetylhydrolase (Km = 23.4
      +/- 7.6 mumol/L) released by adherent human monocytes in culture was found to
      bind preferentially to small, dense LDL subspecies upon incubation of Pefabloc
      inactivated plasma with monocyte supernatant.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7583555
TI  - Inhibitors for the in vitro assembly of Lp(a).
AB  - Lp(a) is composed of an LDL-like core and the glycoprotein apo(a). Current
      evidence strongly suggests that the assembly of this atherogenic lipoprotein
      proceeds outside the liver cells in a two-step fashion. In the first step, a
      loose complex is formed involving kringle-4 motifs in apo(a) and one or more Lys
      side chains in apoB-100. In the second step, this complex is stabilized by a
      disulfide bridge. Indications are that Lp(a) assembly is critical in the
      determination of plasma apo(a) concentrations. Therefore, we searched for
      substances that interfere with the first step of Lp(a) assembly. epsilon
      Aminohexoic acid (epsilon-AHA), known as an inhibitor from earlier assembly
      studies, had an IC50 of 4.8 mmol/L. The IC50 of Pro, HO-p-aminobenzene
      sulfonamide, Lys, N-epsilon-acetyl-Lys, taurine, Glu, serotonin, and benzamidine
      were all > 20 mmol/L. gamma-Aminobutyric acid, spermine, and spermidine exhibited
      IC50 on the same order of magnitude as epsilon-AHA. The substances with the
      highest inhibitory action were tranexamic acid and delta-aminovaleric acid. Seven
      of eight patients treated in a pilot study with tranexamic acid (Cyclocapron)
      responded with a decrease of plasma apo(a) of 18.5 +/- 8.2%. We suggest that
      substances that interfere with the Lp(a) assembly are worth pursuing further for
      their usefulness as therapeutic agents in reducing high plasma Lp(a)
      concentrations.

PMID- 7583556
TI  - Synergistic effects of fluid shear stress and cyclic circumferential stretch on
      vascular endothelial cell morphology and cytoskeleton.
AB  - The development of atherosclerosis is thought to be initiated by a dysfunctional
      state of the vascular endothelium. The proposal that mechanical forces play a
      role in the localization of this disease has led researchers to develop in vitro
      models to assess their effects on cultured endothelial cells. The arterial
      endothelium is exposed simultaneously to circumferential hoop stretch and wall
      shear stress, yet previous investigations have focused on the isolated effects of
      either cyclic stretch or shear stress. The influence of physiological levels of
      combined shear stress and hoop stretch on the morphology and F-actin organization
      of bovine aortic endothelial cells was investigated. Cells subjected for 24 hours
      to shear stresses higher than 2 dyne/cm2 or to hoop stretch greater than 2%
      elongated significantly compared with unstressed controls and oriented along the
      direction of flow and perpendicular to the direction of stretch. Exposure to more
      than 4% stretch significantly enhanced the responses to shear stress. Both shear
      stress and hoop stretch induced formation of stress fibers that were aligned with
      the cells' long axes. Simultaneous exposure to both stimuli appeared to enhance
      stress fiber size and alignment. These results indicate that shear stress and
      hoop stretch synergistically induce morphological changes in endothelial cells,
      which suggests that circumferential strain might modulate sensitivity of
      endothelial cells towards shear stress.

PMID- 7583557
TI  - Coffee consumption, alcohol use, and cigarette smoking as determinants of serum
      total and HDL cholesterol in two Serbian cohorts of the Seven Countries Study.
AB  - The associations between serum total and HDL cholesterol and three lifestyle
      factors--consumption of Turkish coffee, consumption of alcohol, and cigarette
      smoking--were examined in two Serbian cohorts of the Seven Countries Study. In
      1988 and 1989, 319 men from Zrenjanin and Belgrade, 65 to 84 years old and free
      of myocardial infraction, participated. The men from Zrenjanin were originally
      working in a large cooperative, and the men from Belgrade were faculty members of
      the university. HDL cholesterol, alcohol consumption, and cigarette smoking were
      significantly higher in Zrenjanin than in Belgrade. Serum total cholesterol
      levels and coffee consumption were not different. ANCOVA showed that serum total
      cholesterol levels were 8.2% higher (P < .05) in men consuming two small cups of
      coffee per day compared with abstainers, and this was also seen after adjustment
      for cigarette smoking, age, body mass index, cohort, and alcohol consumption. In
      men consuming one or more alcoholic drinks per day (more than 10 g/d alcohol),
      HDL cholesterol levels were increased by 0.19 mmol/L (15.4%) compared with men
      consuming no alcohol (P < .001). This association was stronger in the Zrenjanin
      cohort than in the Belgrade cohort (P < .05). Smoking was not associated with
      total cholesterol or with HDL cholesterol levels. In Serbian men, boiled Turkish
      coffee and alcohol consumption are independently associated with serum total and
      HDL cholesterol levels, respectively.

PMID- 7583558
TI  - Insulin sensitivity, lipids, and blood pressure in young American blacks.
AB  - The purpose of this study was to determine whether insulin resistance was linked
      with alterations in plasma lipids in adult young blacks with borderline
      hypertension. Ninety-four American blacks participated (46 men, 48 women, age
      range 28 to 33 years). Within this group of 94 subjects, there were 60
      normotensive (Nt) subjects and 36 subjects with borderline hypertension (BHt),
      defined as blood pressure > 135/85 mm Hg. None of the subjects were diabetic or
      receiving antihypertension medication. All participants had blood pressure and
      anthropometric measurements, a fasting lipid profile, an oral glucose tolerance
      test, and a euglycemic hyper-insulinemic clamp. Insulin-stimulated glucose
      utilization (M), determined by insulin clamp, was significantly lower in the BHt
      subjects compared with the Nt subjects (men, Nt 6.91 +/- 0.62 versus BHt 5.54 +/-
      0.65; women, Nt 5.97 +/- 0.47 versus BHt 3.79 +/- 0.38 mg.kg-1.min-1, P = .006).
      When M was corrected for adiposity and expressed in milligrams per kilogram of
      fat free mass (M'), the difference between Nt and BHt remained significant (P =
      .006). There was a significant correlation of M' with systolic blood pressure (r
      = .393, P < .0001), HDL-C (r = .382, P < .0001), triglyceride level (r = 308, P <
      .001), apolipoprotein A-I (r = .190, P = .033), and apolipoprotein B stepwise
      multiple linear regression analysis, HDL-C emerged as the most significant lipid
      component in the model for insulin resistance. These data suggest that in
      American blacks with mild hypertension, the risk for cardiovascular disease may
      be augmented in the presence of insulin resistance.

PMID- 7583559
TI  - Effect of diabetes on lipoprotein size.
AB  - The effects of diabetes on lipoprotein particle sizes were assessed using samples
      from 94 subjects with non-insulin-dependent diabetes mellitus. From a larger
      population of nondiabetic subjects who showed normal glucose tolerance, we
      selected an exact match in terms of age, sex, and menopausal status. We designed
      a protocol to make nondenaturing gradient gels for the resolution of LDL
      subfractions and generated two measures of LDL size: diameter of the predominant
      LDL species and proportion of LDL cholesterol (LDL-C) in particles larger than
      25.5 nm (large LDL-C). Similarly, we made two measures of HDL size, large HDL
      cholesterol (HDL-C) and large HDL-apoAI, which represents the proportion of HDL-C
      and apoAI, respectively, occurring on particles larger than HDL-3. In pairwise
      comparisons, diabetes was associated with significantly (P < .004) smaller
      lipoprotein particles for all measures except large HDL-C. Each of the size
      measures was significantly and positively correlated with each of the others,
      suggesting that common metabolic mechanisms influence lipoprotein particle sizes
      across classes of lipoproteins. In addition, each of the size measures was
      correlated with a variety of measures of HDL and beta-lipoprotein concentrations,
      which included HDL-C, LDL-C, triglycerides, and apoAI, apoB, and apoE. We used
      stepwise regression analyses to select from the measures of lipoprotein
      concentrations those independently correlated with each of the lipoprotein size
      measures. After adjusting for these metabolic correlates of lipoprotein size
      measures, we found the effect of diabetes on lipoprotein size measures was no
      longer significant except for a modest effect (P = .027) on large HDL-apoAI.

PMID- 7583564
TI  - Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction
      of cholesteryl ester transfer protein and hepatic triglyceride lipase.
AB  - Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state
      accompanied by a longevity syndrome. However, we reported the cases of markedly
      hyperalphalipoproteinemic subjects with juvenile corneal opacification. The
      patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities,
      and one of them has recently been identified to be homozygous for a missense
      mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP)
      gene. In the current study, to elucidate the clinical significance of and
      atherogenicity in marked HALP, we determined the incidence of atherosclerotic
      cardiovascular disease (ACD) in patients with marked HALP and characterized the
      lipoprotein abnormalities in those who had ACD, focusing especially on CETP and
      HTGL. The subjects were 201 patients (111 males and 90 females) with marked HALP
      ( > or = 2.58 mmol/L [100 mg/dL]), 67% of whom were demonstrated to have the CETP
      gene mutations in the intron 14 splice donor site or in exon 15. Their mean age
      was 54 +/- 15 years. Plasma levels of total cholesterol, HDL cholesterol, and
      triglyceride in all subjects were 6.28 +/- 1.78, 3.15 +/- 0.90, and 1.08 +/- 0.53
      mmol/L, respectively. Ten of the male patients (9.0%) and two of the female
      patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris,
      and peripheral vascular diseases. Ten patients with HALP who had ACD were
      identified to be heterozygotes for CETP deficiency. To further clarify the
      characteristics of marked HALP in patients with ACD, we compared the plasma
      lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP
      deficiency who were with and without ACD.

PMID- 7583561
TI  - Triglycerides are major determinants of cholesterol esterification/transfer and
      HDL remodeling in human plasma.
AB  - Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer
      protein (CETP) are responsible for the esterification of cell-derived cholesterol
      and for the transfer of newly synthesized cholesteryl esters (CE) from HDL to
      apoB-containing lipoproteins in human plasma. LCAT and CETP are also crucial
      factors in HDL remodeling, a process by which HDL particles with a high capacity
      for cell cholesterol uptake are generated in plasma. In the present study,
      cholesterol esterification and transfer were evaluated in 60 patients with
      isolated hypercholesterolemia (HC, n = 20) and isolated (HTG, n = 20) or mixed
      hypertriglyceridemia (MHTG, n = 20) and in 20 normolipidemic healthy individuals
      (NL). Cholesterol esterification rate (CER) and net CE transfer rate (CETR) were
      measured in whole plasma. LCAT and CETP concentrations were determined by
      specific immunoassays. HDL remodeling was analyzed by monitoring changes in HDL
      particle size distribution during incubation of whole plasma at 37 degrees C.
      Mean CER and CETR were 48% and 73% higher, respectively, in hypertriglyceridemic
      (HTG + MHTG) versus normotriglyceridemic individuals. HDL remodeling was also
      significantly accelerated in plasma from hypertriglyceridemic patients. Strong
      positive correlations were found in the total sample between plasma and VLDL
      triglyceride levels and CER (r = .722 and r = .642, respectively), CETR (r = .510
      and r = .491, respectively), and HDL remodeling (r = .625 and r = .620,
      respectively). No differences in plasma LCAT and CETP concentrations were found
      among the various groups except for a tendency toward higher CETP levels in
      hypercholesterolemic patients (+51% in MHTG and +20% in HC) versus control
      subjects (NL). By stepwise regression analysis, VLDL triglyceride level was the
      sole significant predictor of CER and CETR and contributed significantly together
      with baseline HDL particle distribution to HDL remodeling. These results indicate
      that plasma triglyceride level is a major factor in the regulation of cholesterol
      esterification/transfer and HDL remodeling in human plasma, whereas LCAT/CETP
      concentrations play a minor role in the modulation of reverse cholesterol
      transport.

PMID- 7583565
TI  - In vivo activation of met tyrosine kinase by heterodimeric hepatocyte growth
      factor molecule promotes angiogenesis.
AB  - Hepatocyte growth factor (HGF) is a powerful motogen and mitogen for epithelial
      cells. The factor is a 90-kD heterodimer composed of an alpha chain containing
      four kringle motifs and a beta chain showing structural homologies with serine
      proteases. It is, however, devoid of enzymatic activity. Recently, it has been
      reported that HGF activates migration and proliferation of endothelial cells and
      is angiogenic. In this article we discuss (1) the molecular domains of HGF
      required to activate in vitro and in vivo endothelial cells, studied by use of
      molecular mutants, and (2) the characteristics of the angiogenic response to HGF
      in an experimental model system of implanted reconstituted basement membrane
      (Matrigel). Two groups of mutants were made and used in vitro and in vivo: one
      with deletions of kringle domains and one with substitution at the cleavage site
      of the HGF precursor. In vitro, HGF variants containing only the first two (HGF
      NK2) or the first three kringles (HGF-NK3) of the alpha chain did not induce
      proliferation of endothelial cells even if used at concentration 160-fold higher
      than that optimal for HGF (0.05 nmol/L). High concentrations of these mutants (4
      to 8 nmol/L) activated a little endothelial cell motogenic response that was 60%
      lower than that elicited by HGF. Substitution of Arg 489 with Gln 489 in the HGF
      precursor generated an uncleavable single-chain factor, unable to induce either
      endothelial cell migration or proliferation. In vivo, HGF induced a dose
      dependent angiogenic response, which was enhanced by heparin.

PMID- 7583563
TI  - Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL
      subfraction patterns in normolipemic men and women.
AB  - VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were
      quantified in 304 normolipemic subjects together with postheparin plasma lipase
      activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of
      VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal
      range, but the association of plasma TGs with VLDL1 showed a steeper slope than
      that of VLDL2 (P < .001). Plasma TG level was the most important determination of
      LDL subfraction distribution. The least dense species, LDL-I, decreased as the
      level of this plasma lipid rose in the population. LDL-II in both men and women
      exhibited a positive association with plasma TG level in the range 0.5 to 1.3
      mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range
      the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed
      little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in
      LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS).
      Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL
      III concentrations in men than in women (P < .001); 42% of the men had and LDL
      III in the range associated with high risk of heart disease ( > 100 mg
      lipoprotein/dL plasma) compared with only 17% of the women. Other influences on
      the LDL subfraction profile were the activities of lipases and parameters
      indicative of the presence of insulin resistance. Men on average had twice the
      hepatic lipase activity of women. This enzyme was not strongly associated with
      variation in the LDL subfraction profile in men, but in women it was correlated
      with LDL-III (r = 39, P = .001) and remained a significant predictor in
      multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose
      were correlated negatively with LDL-I and positively with LDL-III, primarily, at
      least in the case of LDL-III, through raising plasma TGs. On the basis of these
      cross-sectional observations we postulate the following model for the generation
      of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number
      of reasons, including failure of insulin action. The increase in the
      concentration of VLDL1 expands the plasma TG pool, and this, via the action of
      cholesteryl ester transfer protein (which facilitates neutral lipid exchange
      between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the
      major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7583562
TI  - Association of postprandial triglyceride and retinyl palmitate responses with
      newly diagnosed exercise-induced myocardial ischemia in middle-aged men and
      women.
AB  - Although strong evidence exists linking fasting plasma levels of LDL cholesterol
      (LDL-C) and HDL cholesterol (HDL-C) to risk for development of coronary artery
      disease (CAD), the data in support of an independent role for fasting
      triglyceride (TG) concentrations are weak. Humans are in the postprandial state
      most of the day, however, and results from both basic and clinical studies
      suggest that postprandial TG levels may be atherogenic. Previous studies have
      not, however, attempted to determine if postprandial TG levels are associated
      with CAD independent of other traditional risk factors or plasma lipid levels,
      particularly fasting plasma concentrations of TG and HDL-C. Ninety-two men and
      113 women (mean age, 51.6 and 53.6 years, respectively) were recruited from
      populations undergoing diagnostic exercise electrocardiographic or thallium
      stress tests at our medical centers. Twenty-six men and 24 women had positive
      tests. We chose exercise-induced myocardial ischemia (EIM) as the criterion for
      defining case and control subjects because we wanted participants who did not
      have a prior diagnosis of CAD. Blood samples were obtained for measurement of
      plasma TG, TG-rich lipoprotein TG, and retinyl palmitate (RP) levels 2, 3.5, 5,
      and 8 hours after the subjects had consumed a fatty test meal. Logistic
      regression models were developed to test for associations between each variable
      and case-control status. Among men but not women postprandial TG and RP responses
      were associated with EIMI independent of age, race, and smoking status. In the
      male group, the odds ratio (OR) for an increase in postprandial TG response of
      approximately 1 SD was 1.69 (P = .007); the OR for an increase in RP response of
      1 SD was 2.47 (P = .011). However, when fasting TG was added to the model, the OR
      for postprandial TG area in the men was reduced to 1.44 (P = .17); the OR
      postprandial RP area in the men was reduced to 1.88 (P = .12). There was no
      effect of adding other risk factors, including LDL-C and HDL-C, to the model.
      Significant effect modification by body mass index (BMI) on the relationship
      between postprandial responses and case-control status was observed. In men with
      BMI < 30, the OR was 1.83 for postprandial TG (P = .041) and 2.77 for
      postprandial RP (P = .032) in models that included fasting TG, LDL-C, and
      hypertension.

PMID- 7583560
TI  - Serum paraoxonase activity, concentration, and phenotype distribution in diabetes
      mellitus and its relationship to serum lipids and lipoproteins.
AB  - Human serum paraoxonase is physically associated with HDL and has been implicated
      in the detoxification of organophosphates and possibly in the prevention of LDL
      lipid peroxidation. We investigated the serum activity and concentration of
      paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2
      diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally
      lower in diabetics than in control subjects. This decrease was unrelated to
      differences in paraoxonase phenotype distribution or its serum concentration.
      Rather, the difference in paraoxonase activity was explained by its specific
      activity, which was lower in diabetics, indicating either the presence of a
      circulating inhibitor or disturbance of the interaction of paraoxonase with HDL
      affecting its activity. Paraoxonase specific activity was lowest in patients with
      peripheral neuropathy, suggesting an association of paraoxonase with neuropathy.
      In control subjects but not patients with diabetes, paraoxonase correlated with
      HDL cholesterol and apolipoprotein A-1. Our results indicate that the low
      paraoxonase activity in diabetes is due to decreased specific activity. In other
      studies low serum paraoxonase activity has been associated with increased
      susceptibility to atherosclerosis, and the present results also suggest an
      association with peripheral neuropathy, which could be due to reduced capacity to
      detoxify lipid peroxides in diabetes.

PMID- 7583566
TI  - A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I
      gene without evidence of coronary heart disease.
AB  - We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as
      data from members of his family. Corneal opacity and a stomatocyte were found but
      not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol,
      apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and
      175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and
      apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase
      activity was half of normal, while lipoprotein lipase and hepatic triglyceride
      lipase activities were within normal limits. ApoA-I deficiency was confirmed by
      combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of
      the patient and five of his family members by direct sequencing after
      amplification by polymerase chain reaction and found a codon 8 nonsense mutation
      (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a
      pedigree analysis by DNA sequencing and restricted fragment length polymorphism
      (Sty I) were consistent with an autosomal codominant trait. Coronary angiography
      was performed to evaluate coronary atherosclerosis, but no significant luminal
      narrowing was detected. An intracoronary ultrasound study showed mild intimal
      hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without
      evidence of coronary heart disease.

PMID- 7583567
TI  - Lipid composition of HDL subfractions in dog plasma and lymph.
AB  - We report the lipid composition of dog plasma and peripheral lymph lipoproteins
      as separated into pre-beta, alpha, and pre-alpha fractions by agarose gel
      electrophoresis. Plasma lipoproteins with alpha mobility have a composition
      different from that of plasma lipoproteins with pre-alpha mobility, having 9%
      versus 11% free cholesterol, 21% versus 17% cholesterol ester, 1% versus 16%
      triacylglycerol, and 69% versus 56% phospholipid. On the other hand, lymph alpha
      and pre-alpha lipoproteins have compositions that are quite similar (9% versus 7%
      free cholesterol, 17% versus 17% cholesterol ester, 2% versus 4% triacylglycerol,
      and 71% versus 71% phospholipid). The lipid compositions of plasma and lymph
      alpha lipoproteins are quite similar (9% versus 9% free cholesterol, 21% versus
      17% cholesterol ester, 1% versus 2% triacylglycerol, and 70% versus 72%
      phospholipid). The lipid compositions of plasma and lymph pre-alpha lipoproteins
      are different (11% versus 7% free cholesterol, 17% versus 17% cholesterol ester,
      16% versus 4% triacylglycerol, and 56% versus 71% phospholipid). Peripheral lymph
      lipoproteins with pre-beta mobility contained 15% cholesterol, 13% cholesterol
      ester, 10% triacylglycerol, and 61% phospholipid. Compared with plasma,
      peripheral lymph lipoproteins are free cholesterol-enriched in all fractions.
      Calculated stoichiometric ratios of lipid to apoA-I per particle, alpha
      lipoproteins have two molecules of apoA-I per particle, and pre-alpha
      lipoproteins have four molecules of apoA-I per particle.

PMID- 7583568
TI  - Intravenous injection of rabbit apolipoprotein A-I inhibits the progression of
      atherosclerosis in cholesterol-fed rabbits.
AB  - The effects of intravenous injection of purified rabbit apoA-I on the progression
      of aortic atherosclerosis in cholesterol-fed rabbits were examined. In experiment
      1, 28 rabbits were equally divided into groups A and B and fed a 0.5% cholesterol
      diet for 90 days. For the last 30 days, group B received 40 mg apoA-I every week.
      The fatty streak lesions in group B (23.9 +/- 15.6%) were significantly
      suppressed compared with those in group A (46.0 +/- 24.9%) (P < .05). In
      experiment 2, 33 rabbits were divided into four groups (8 or 9 rabbits per group)
      and fed a 0.5% cholesterol diet. Group A was killed on day 105, while groups B,
      C, and D were maintained for an additional 60 days on a normal diet, during which
      time groups C and D received 1 mg apoA-I every other day or 40 mg apoA-I every
      week, respectively. The lesions in group C (70.2 +/- 15.4%) and group D (65.7 +/-
      20.0%) were significantly suppressed compared with those in group B (86.2 +/-
      13.7%) (P < .05) but were not reduced to the level of group A (50.0 +/- 22.9%).
      Although apparent regression was not observed under these conditions, the present
      study provided the first evidence for the antiatherogenic effect of homologous
      and apoA-I on the progression of atherosclerosis in cholesterol-fed rabbits.

PMID- 7583572
TI  - Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta
      analysis.
AB  - The objective of this study was to examine whether oils high in monounsaturated
      or polyunsaturated fats have a differential effect on serum lipid levels, using a
      meta-analytical approach. Fourteen studies (1983 through 1994) were identified
      that met six inclusion criteria, the primary criterion being that a study have at
      least two intervention diets that varied in monounsaturated and polyunsaturated
      fat content but were otherwise similar in total fat, saturated fat, fiber, and
      dietary cholesterol. Seven studies included a comparable high-saturated fat diet.
      Standardized effect sizes observed treatment difference in mean end-point lipid
      levels, divided by the pooled (SD) were calculated for individual studies, then
      individual effect sizes were pooled. The results indicated no significant
      differences in total, LDL, or HDL cholesterol levels when oils high in
      monounsaturated or polyunsaturated fats were compared directly. Triglyceride
      levels were modestly but consistently lower on the diets high in polyunsaturated
      fats (P = .05). Replacement of saturated fat with either monounsaturated or
      polyunsaturated fat led to significant decreases in total and LDL cholesterol (P
      < .001), and the pooled effect sizes were comparable for either type of
      unsaturate (effect sizes ranged from -0.64 to -0.68, ie, roughly a decrease of
      0.65 mmol/L [25 mg/dL] relative to the high-saturated fat diets). Neither type of
      unsaturated fat significantly changed HDL cholesterol or triglyceride levels
      relative to the high-saturated fat diets. In conclusion, the evidence from this
      meta-analysis strongly indicates there is no significant difference in LDL or HDL
      cholesterol levels when oils high in either monounsaturated or polyunsaturated
      fats are exchanged in the diet. Any dietary recommendations for the use of one in
      preference to the other should be based on outcomes other than serum cholesterol
      levels.

PMID- 7583569
TI  - Overexpression of human apolipoprotein B-100 in transgenic rabbits results in
      increased levels of LDL and decreased levels of HDL.
AB  - In this study, and 80-kb human genomic DNA fragment spanning the human apoB gene
      was used to generate transgenic New Zealand White rabbits that expressed human
      apoB-100. The concentration of human apoB in the plasma of the transgenic rabbits
      ranged between 5 and 100 mg/dL. The transgenic rabbits had nearly threefold
      elevations in the plasma levels of triglycerides and cholesterol compared with
      nontransgenic controls. Nearly all the cholesterol and human apoB in the plasma
      was in the LDL fraction. Pronounced triglyceride enrichment of the LDL fraction
      was a striking feature of human apoB overexpression in the transgenic rabbits, in
      which the LDL fraction contained more than 75% of the plasma triglycerides. The
      triglyceride-enriched LDL particles were smaller and more dense than the native
      rabbit LDL and contained markedly increased amounts of apoE and apoC-III. In the
      nontransgenic control animals most of the triglycerides were in the VLDL, and
      most of the apoE and apoC-III were in the VLDL and HDL fractions. In addition to
      increased LDL levels, overexpression of human apoB in rabbits resulted in lower
      plasma levels of HDL cholesterol and apoA-I. In our prior studies on transgenic
      mice expressing human apoB, we documented triglyceride-rich LDL and reduced
      levels of HDL cholesterol. These prior findings in mice, together with the
      present findings in transgenic rabbits, suggest that triglyceride-rich LDL and
      lowered levels of HDL cholesterol may be hallmark features of apoB
      overexpression.

PMID- 7583570
TI  - Level of apolipoprotein B mRNA has an important effect of the synthesis and
      secretion of apolipoprotein B-containing lipoproteins. Studies on transfected
      hepatoma cell lines expressing recombinant human apolipoprotein B.
AB  - The effect of apoB mRNA level on hepatic apoB production has not been studied
      extensively, primarily because the steady state level of apoB mRNA cannot be
      altered on a short-term basis. We studied the effect of vastly different apoB
      mRNA levels on the synthesis and secretion of apoB-containing lipoproteins using
      rat hepatoma (McA-RH7777) cell lines transfected with cDNA constructs encoding
      human apoB53 (the amino-terminal 53% of the protein; hapoB53) or apoB100
      (hapoB100). Among the three hapoB53-transfected cell lines, the relative steady
      state levels of the hapoB53 mRNA were 10:2.5: < 0.1. Correspondingly, the
      relative concentration of the intracellular hapoB53 protein was 8:3:1 and of the
      medium hapoB53 (accumulated over a period of 18 hours) was 12:4:1, which
      positively correlates with the hapoB53 (d = 1.06 to 1.21 g/mL) or endogenous rat
      apoB100 (d < 1.06 g/mL). When cell lines containing high or intermediate hapoB53
      mRNA levels were compared, there was an eightfold increase in the synthesis and a
      twofold increase in the secretion efficiency of hapoB53. Analysis of the
      synthesis and secretion of lipids revealed that in cells producing high levels of
      hapoB53, triglyceride synthesis (twofold) and secretion (twofold to threefold)
      were also increased. Furthermore, with the three hapoB100-transfected cells we
      also observed an increase in apoB100 synthesis (three-fold), apoB100 secretion
      efficiency (twofold), triglyceride synthesis (fourfold to fivefold), and
      triglyceride secretion (fourfold to fivefold) in the cells expressing high levels
      of hapoB100. In all the cell lines examined, secretion efficiency of endogenous
      rat apoA-I was not affected by transfection. Together these data suggest that
      secretion of apoB-containing triglyceride-rich lipoproteins can be influenced by
      the level of apoB mRNA or the rate of apoB translation.

PMID- 7583571
TI  - Relative contributions of apolipoprotein(a) and apolipoprotein-B to the
      development of fatty lesions in the proximal aorta of mice.
AB  - Transgenic mice expressing transgenes for both human apolipoprotein B-100 (h
      apoB) and apolipoprotein(a) [apo(a)] were fed a high-fat, atherogenic diet for 14
      weeks to examine the effect of lipoprotein(a) [Lp(a)]on the development of aortic
      fatty lesions. The extent of lesions in the proximal region of the aorta of Lp(a)
      mice was measured by use of a computer-assisted image analysis of 20 sections per
      animal and compared with that of nontransgenic mice as well as mice expressing
      either the apo(a) or h-apoB transgene. The control (n = 23) and apo(a) (n = 22)
      transgenic mice had very small mean lesions areas (607 versus 128 microns2 per
      section). The h-apoB-expressing mice (n = 20) had significantly higher mean
      lesion areas (3288 microns2 per section) than either the control or apo(a)
      transgenic animals. Coexpression of apo(a) and h-apoB transgenes resulted in only
      a modest increase in lesion area (4678 microns2 per section, n = 19). Thus, the
      expression of human apo(a) in C57BL/6/SJL hybrid mice fed an atherogenic diet
      failed to significantly potentiate the development of aortic fatty lesions in the
      absence or presence of high levels of h-apoB.

PMID- 7583573
TI  - Selective increase in cholesterol at atherosclerosis-susceptible aortic sites
      after short-term cholesterol feeding.
AB  - In rabbits, the aortic arch and branch sites of the descending thoracic and
      abdominal aortas are susceptible to atherosclerosis. This study investigated the
      hypothesis that the reported focal increase in LDL concentration and mean
      residence time at susceptible aortic sites after feeding cholesterol for 4 to 8
      days precede atherosclerotic change as indicated by increased aortic cholesterol
      concentration. Cholesterol concentrations for all aortic sites of normal rabbits
      were similar (approximately equal to 2.8 mumol/g). No change in aortic
      cholesterol concentration could be detected after feeding cholesterol for 8 days.
      However, after feeding cholesterol for 12 and 16 days, cholesterol concentrations
      for abdominal branch sites were increased compared with abdominal branch sites of
      normal rabbits (4.47 +/- 0.50, n = 8, and 4.85 +/- 0.33, n = 11, mumol/g,
      respectively, versus 2.87 +/- 0.27, n = 12, mumol/g; P < .025 and P < .005,
      respectively). In contrast, the cholesterol concentration of atherosclerosis
      resistant nonbranch abdominal aorta was unchanged after feeding cholesterol for
      16 days and was much less than that of the branch sites (2.72 +/- 0.12 versus
      4.85 +/- 0.33, mumol/g, n = 11; P < .001). Cholesterol concentrations for other
      susceptible sites were also increased after feeding cholesterol for 12 and 16
      days. Cholesterol concentrations for susceptible sites were linearly related to a
      combined measure of duration and extent of hypercholesterolemia (P < .001 to P <
      .0001), whereas no such relationship could be detected for resistant sites. Most
      (59% to 93%) of the cholesterol accumulating in susceptible aortic sites after
      feeding cholesterol for 12 and 16 days was nonesterified, suggesting that the
      increased cholesterol concentration did not reflect development of foam cells or
      the insudation of plasma lipoproteins. This study suggests that the reported
      focal increases in LDL concentration and mean residence time at susceptible
      aortic sites during cholesterol feeding precede atherosclerosis.

PMID- 7583574
TI  - Reduction of serum cholesterol levels alters lesional composition of
      atherosclerotic plaques. Effect of pravastatin sodium on atherosclerosis in
      mature WHHL rabbits.
AB  - We examined whether serum cholesterol reduction alters the lesional composition
      of atherosclerotic plaques. To reduce serum cholesterol levels, we gave
      pravastatin sodium, a 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor,
      to mature Watanabe heritable hyperlipidemic rabbits, an LDL receptor-deficient
      animal model, for 48 weeks. Atherosclerotic lesions were immunohistochemically
      and conventionally stained and each lesional component area was measured by a
      color image analyzer. Compared with those of a placebo group, serum LDL
      cholesterol levels were reduced by 22% (P<.05). Data for atherosclerosis
      indicated a significant decrease in percent of surface lesion area (26%
      reduction) and in intimal thickening (30% reduction) in the abdominal aorta, as
      well as in coronary stenosis (29% reduction). Data for lesional composition
      indicated a significant decrease in the percent area of macrophage plus
      extracellular lipid deposits in aortic lesions (32% reduction) and coronary
      lesions (45% reduction). A significant increase was observed in the percent area
      of collagen in aortic lesions and in the percent area of smooth muscle cells in
      coronary lesions. The plaques seemed to become stable lesions as a result of
      pravastatin treatment. In conclusion, a long-term reduction of serum LDL
      cholesterol reduced lipid-related lesional components, in addition to suppressing
      the progression of established atherosclerosis.

PMID- 7583575
TI  - Mechanism of inhibition of neointimal formation by the angiotensin-converting
      enzyme inhibitor cilazapril. A study in balloon catheter-injured rat carotid
      arteries.
AB  - We investigated the mechanism of inhibition of neointima formation by the
      angiotensin-covering enzyme the carotid artery. We looked for the effects of
      cilazapril on all phases of the response to injury, ie, on proliferation of
      smooth muscle cells (SMCs) in the media, their migration, their proliferation in
      the neointima, and their disposition of extracellular matrix in the neointima.
      Although treatment was discontinued after 2 weeks, the inhibitory effect of
      cilazapril on neointimal formation was evident even 52 weeks after injury. The
      amount of extracellular matrix deposited in the intima during cilazapril
      treatment was decreased by 20% 2 weeks after injury, but no effect was seen if
      tissues were analyzed at 4 or 52 weeks. [3H]Thymidine-labeled cells (pulse
      labeling as well as 14-day continuous labeling) showed a decrease in SMC labeling
      in the tunica medica by 50%, but no inhibition in the labeling indices was seen
      in the neointima. The fraction of unlabeled neointimal cells in the cilazapril
      treated rats as judged from continuous labeling experiments was inhibited by 86%.
      Taken together, these data suggest an antiproliferative effect on medial SMCs and
      an inhibition of SMC migration into the intima by cilazapril. Since intimal
      extracellular matrix deposition was only delayed, the decrease in medial SMC
      proliferation and subsequent migration seems to be the main reason for the
      reduction of neointima formation.

PMID- 7583576
TI  - In vivo effect of TGF- beta 1. Enhanced intimal thickening by administration of
      TGF- beta 1 in rabbit arteries injured with a balloon catheter.
AB  - The in vivo effect of transforming growth factor-beta 1 (TGF-beta 1) was studied
      in a model system in which arterial intimal thickening was induced by injury of
      rabbit arteries with a balloon catheter (BCI). Intimal area and its ratio to
      medial area in carotid arteries after BCI were significantly higher in rabbits
      treated with 10 micrograms/kg TGF-beta 1 and 10 mg/kg aspirin i.v. QD (TGF-beta 1
      group) than in those treated with 10 mg/kg aspirin i.v. QD only (control group).
      Intimal cell numbers in the TGF-beta 1 and control groups were not significantly
      different from each other, but matrix volume in the intimal layer was
      significantly higher in the TGF-beta 1 group. By immunohistochemical and Northern
      blot analyses, the fibronectin content in carotid intimal and medial layers was
      greater in the TGF-beta 1 group compared with that in the control group. Thus, in
      intimal thickenings induced by BCI. TGF-beta 1 mainly enhanced the formation of
      matrix containing fibronectin. Moreover, the mRNAs of TGF-beta 1 and type II
      receptors were detected in carotid arteries 7 and 14 days after, but not before,
      BCI. Thus, TGF-beta 1 influences the process of intimal thickening induced by BCI
      through a receptor-mediated mechanism in vivo. The significance of this fact is
      discussed in relation to the development of atherosclerosis.

PMID- 7583578
TI  - Lipoproteins regulate C-type natriuretic peptide secretion from cultured vascular
      endothelial cells.
AB  - We have shown that oxidized low-density lipoprotein (Ox-LDL) modulates various
      endothelial cell (EC) functions. C-type natriuretic peptide (CNP), the third
      member of the natriuretic peptide family to be discovered, is secreted from
      peripheral vascular ECs and regulates body fluid homeostasis, vascular tone, and
      vascular growth. This study was designed to investigate the effects of
      lipoproteins on CNP secretion from cultured ECs. Treatment of bovine carotid ECs
      with OX-LDL and its extracted lipids resulted in a concentration-dependent
      suppression of the spontaneous and transforming growth factor-beta 1-stimulated
      secretion CNP. Native LDL, its extracted lipids, and acetylated LDL were
      inactive. OX-LDL depleted of its amphiphilic lipids, which was prepared by
      incubation with defatted albumin, lost its suppressive effect on CNP secretion. 7
      Ketocholesterol, one of the amphiphilic lipids in OX-LDL that is transferable
      from OX-LDL to defatted albumin, suppressed CNP secretion by ECs, thus mimicking
      the effect of OX-LDL. Coincubation with high-density lipoprotein (HDL), which
      alone had no effect on CNP release, significantly prevented OX-LDL-induced
      inhibition of CNP secretion by ECs. Analysis by thin-layer chromatography
      demonstrated that oxysterols, including 7-ketocholesterol, in OX-LDL were
      transferred from OX-LDL to HDL during coincubation of these two lipoproteins.
      These results indicate that OX-LDL suppresses CNP secretion from ECs by 7
      ketocholesterol or other transferable hydrophilic lipids in OX-LDL, and the
      suppressive effect of OX-LDL is reversed by HDL. Lipoproteins thus may regulate
      CNP secretion from the endothelium of atherosclerotic arteries.

PMID- 7583577
TI  - Balloon catheterization induced arterial expression of embryonic fibronectins.
AB  - Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins
      that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and
      EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during
      embryogenesis, expressed to lesser degrees in normal adult tissues, and may be
      locally reexpressed at adult tissue injury. RNase mapping shows that normal rat
      arteries express low levels of FNs that are predominantly EIIIA- and EIIIB-.
      Following balloon injury, arterial walls produce increased total levels of FN
      transcripts that preferentially include both the EIIIA and EIIIB segments.
      However, despite inducing increased total FN mRNA, balloon injury does not alter
      the relative composition of V120+, V95+, AND V0 spliced forms. In situ
      hybridization reveals that as early as 4 days after injury medial cells express
      increased total FN mRNA, and by 7 days substantial neointimal and focal medial
      synthesis of EIIIA+, EIIIB+, and V120+ FNs occurs; macrophages do not
      significantly contribute to this observed vascular FN synthesis. Consistent with
      the mRNA data, immunofluorescence microscopic analysis reveals increased
      deposition of EIIIB+ and V+ FN protein forms in injured arterial walls,
      particularly within the neointima. Our results suggest that local synthesis of
      specific FN isoforms is important to the neointimal formation that ensues after
      balloon injury.

PMID- 7583579
TI  - HDL3 stimulates multiple signaling pathways in human skin fibroblasts.
AB  - The influence of HDL3 on phospholipid breakdown was examined in human skin
      fibroblasts. HDL3 elicited phosphatidylcholine (PC) and phosphatidylinositol (PI)
      turnover and activated multiple phospholipases. In [14C]lyso-PC-labeled or
      [14C]choline (Cho)-labeled cells, a biphasic activation of PC-specific
      phospholipase D (PLD) with peak maxima 30 to 60 seconds and 5 to 7 minutes after
      stimulation with 20 micrograms/mL HDL3 was shown by (1) a 1.5- to 3-fold increase
      in Cho release, and (3) transphosphatidylation of PC to phosphatidylbutanol in
      the presence of 0.3% butanol. Activation of PC-specific PLD was paralleled by an
      activation of PC-specific phospholipase C (PLC). A significant increase in
      [14C]diacylglycerol (DG) was seen from 2 minutes after stimulation onward and
      remained for at least 2 hours. By means of butanol, the PA-phosphohydrolase (PPH)
      inhibitor propranolol, and the PC-PLC inhibitor D609, we demonstrated that the
      initial PC-derived DG formation occurred primarily by a coupled PLD/PPH pathway
      and that a major part of the sustained DG formation was derived directly from PC
      by PC-PLC. By down-regulating protein kinase C (PKC) we demonstrated that PKC
      activates PC-PLC and desensitizes PC-PLD at no longer incubation times. The
      sustained PC hydrolysis as well as HDL3-mediated PI turnover and PC resynthesis
      was observed on stimulation with 5 to 75 micrograms/mL HDL3, whereas the rapid
      activation of PC-PLD/PPH was detected only on stimulation with HDL3 at
      concentrations of between 10 and 75 micrograms/mL. Only the latter response could
      be mimicked by apolipoprotein A-I and apolipoprotein A-II proteoliposomes, and
      only this response was inducible by cholesterol loading. The HDL3-mediated second
      messenger responses were inhibited by modification of HDL3 by tetranitromethane
      and could not be mimicked by protein-free liposomes. These data suggest that HDL3
      induced cell signaling in human skin fibroblasts is mediated by specific protein
      receptor interaction and that more than one agonist activity may be involved.

PMID- 7583580
TI  - High-density lipoproteins inhibit cytokine-induced expression of endothelial cell
      adhesion molecules.
AB  - While an elevated plasma concentration of HDLs is protective against the
      development of atherosclerosis and ensuing coronary heart disease (CHD), the
      mechanism of this protection is unknown. One early cellular event in
      atherogenesis is the adhesion of mononuclear leukocytes to the endothelium. This
      event is mediated principally by vascular cell adhesion molecule-1 (VCAM-1) but
      also involves other molecules, such as intercellular adhesion molecule-1 (ICAM-1)
      and E-selectin. We have investigated the effect of isolated plasma HDLs and
      reconstituted HDLs on the expression of these molecules by endothelial cells. We
      show that physiological concentrations of HDLs inhibit tumor necrosis factor
      alpha (TNF-alpha) or interleukin-1 (IL-1) induction of these leukocyte adhesion
      molecules in a concentration-dependent manner. Steady state mRNA levels of TNF
      alpha-induced VCAM-1 and E-selectin are significantly reduced by physiological
      concentrations of HDLs. An an HDL concentration of 1 mg/mL apolipoprotein A-I,
      the protein expressions of VCAM-1, ICAM-1, and E-selectin were inhibited by 89.6
      +/- 0.4% (mean +/-SD, n=4), 64.8 +/- 1.0%, and 79.2 +/- 0.4%, respectively. In
      contrast, HDLs have no effect on the expression of platelet endothelial cell
      adhesion molecule (PECAM) or on the expression of the p55 and p75 subunits of the
      TNF-alpha receptor. HDLs were effective when added from 16 hours before to 5
      minutes after cytokine stimulation. HDLs had no effect on TNF-alpha-induced
      expression of ICAM-1 by human foreskin fibroblasts, suggesting that the effect is
      cell-type restricted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583582
TI  - Beta-glycerophosphate accelerates calcification in cultured bovine vascular
      smooth muscle cells.
AB  - Calcification is a common feature of advanced atherosclerotic lesions and is
      being reemphasized as a clinically significant element of vascular disease.
      However, the scarcity of in vitro models of vascular calcification preclude
      studying its molecular and cellular mechanism. In the present study, we describe
      an in vitro calcification in which diffuse calcification can be induced by
      culturing bovine vascular smooth muscle cells (BVSMC) in the presence of beta
      glycerophosphate, ascorbic acid, and insulin in a manner analogous to in vitro
      mineralization by osteoblasts. Calcification was confirmed by von Kossa staining
      and 45Ca accumulation. Factor analysis revealed that beta-glycerophosphate is the
      most important factor for this calcification process, suggesting that alkaline
      phosphatase (ALP) may be involved. As predicted, high levels of ALP expression
      were detected by ALP assay and Northern blot analysis. Functional significance of
      ALP was confirmed by demonstrating that levamisole, a specific inhibitor of ALP,
      inhibited BVSMC calcification in a dose-dependent manner. Bisphosphonates such as
      etidronate and pamidronate potently inhibited BVSMC calcification, suggesting
      that hydroxyapatite formation may be involved. Importantly, expression of
      osteopontin mRNA was dramatically increased in calcified BVSMC compared with
      uncalcified control cells. These data suggest that beta-glycerophosphate can
      induce diffuse calcification by an ALP-dependent mechanism and that this in vitro
      calcification system is useful for analyzing the molecular and cellular
      mechanisms of vascular calcification.

PMID- 7583581
TI  - Expression of the macrophage scavenger receptor in atheroma. Relationship to
      immune activation and the T-cell cytokine interferon-gamma.
AB  - Scavenger receptors mediate internalization of modified lipoproteins and foam
      cell transformation of monocyte-derived cytokines. We investigated macrophage
      scavenger receptor (MSR) expression in monocyte-macrophages from human peripheral
      blood and in atherosclerotic lesions and analyzed its relationship to T
      lymphocytes and immunoregulatory cytokines by immunohistochemistry and polymerase
      chain reaction (PCR). Antibodies specific for the two MSR isoforms were generated
      by immunizing rabbits with isoform-specific synthetic peptides conjugated to
      keyhole limpet hemocyanin. In human atherosclerotic plaques, these antibodies
      stained macrophages and foam cells in a pattern that corresponded to the
      distribution of the macrophage marker CD68. CD3-positive T cells and alpha-actin
      positive smooth muscle cells exhibited no reactivity to the anti-MSR antibodies.
      The frequency of cells stained with antibodies to MSR type I was equal to that of
      cells stained for type II, suggesting that most macrophages coexpress both
      isoforms. Reverse transcription (RT)-PCR analysis confirmed that both MSR
      isoforms were expressed in all plaques examined. There was, however, a tendency
      toward a lower immunohistochemical staining intensity for MSR type I and a
      decreased number of lipid-rich foam cells in T cell-rich areas. The mRNAs for
      interleukin-2 and interferon-gamma, two major products of activated T cells, were
      detected by RT-PCR in all plaques tested. This indicates that activation of T
      lymphocytes occurs in atherosclerotic plaques. Since interferon-gamma
      downregulates MSR expression, these observations suggest a potential mechanism
      for local regulation of MSR expression in the atherosclerotic plaque.

PMID- 7583583
TI  - Osteopontin is not a marker for proliferating human vascular smooth muscle cells.
AB  - Osteopontin (OP) is a secreted glycoprotein that contains the Arg-Gly-Asp (RGD)
      cell-binding sequence that binds calcium and is chemotactic and adhesive for rat
      vascular smooth muscle cells (VSMCs). OP gene expression is upregulated in
      cultured rat VSMCs in vitro and after balloon carotid injury in vivo, suggesting
      that OP may be a marker for proliferating VSMCs in vivo and in vitro. Our in situ
      hybridization studies of human atherosclerotic coronary vessels, however, have
      shown OP mRNA expression in plaque macrophages but not VSMCs. The current study
      investigated OP mRNA expression in cultured human VSMCs and macrophages and in an
      organ culture model of neointima formation in human saphenous vein. OP mRNA
      expression was not detected by Northern blot analysis of total RNA from
      subconfluent or confluent cultures of human VSMCs of any passage maintained in
      normal growth medium or after stimulation with TGF beta 1 (20 ng/mL), angiotensin
      II (1 mumol/L), or basic fibroblast growth factor (10 mg/mL) but was just
      detectable after stimulation with activation vitamin D3 (1 mumol/L). In contrast,
      cultured human macrophages expressed high levels of OP mRNA that were not
      dependent on lipid loading. OP mRNA was detected in isolated foci in all layers
      of saphenous veins maintained in organ culture for 14 days, including <2% of
      neointimal cells, a distribution that paralleled that of tissue macrophages.
      These results suggest that OP gene expression is not a marker for proliferation
      of human VSMCs in vitro and highlight a fundamental difference in the biology of
      human and rodent VSMCs.

PMID- 7583584
TI  - Stimulation of Gs and inhibition of Gi protein functions by minimally oxidized
      LDL.
AB  - We have previously shown that treatment of aortic endothelial cells with
      minimally oxidized LDL (MM-LDL) induces their interaction with monocytes but not
      neutrophils and that these induced responses are associated with increased cAMP
      levels. Here we studied the mechanism of by which MM-LDL elevates cAMP levels.
      Treatment of human aortic endothelial cells with MM-LDL resulted in a saturable
      dose-dependent increase in cAMP levels. Studies using a combination of pertussis
      toxin and MM-LDL suggested that part of the cAMP increase was due to the
      stimulation of Gs complexes. Studies with pertussis toxin-treated membranes in
      which Gi was completely inhibited were used to directly address the effect of MM
      LDL on the Gs pathway. MM-LDL and an oxidized lipid (palmitoyl arachidonyl
      phosphatidylcholine), the effects of which mimic those of MM-LDL, caused a 40% to
      100% increase in cAMP levels in these isolated membranes that was augmented by
      GTP, thus showing Gs stimulation. These results also show that MM-LDL increases
      cAMP levels by inhibiting Gi. MM-LDL inhibited ADP ribosylation of Gi by about
      30% and completely abolished the ability of serotonin to interact with Gi
      complexes, whereas direct activation of Gi by mastoparan was not inhibited. This
      observation suggests that MM-LDL interferes with the interaction of Gi molecules
      with inhibitory receptors. There was no direct effect of MM-LDL on adenylate
      cyclase. Overall, these studies show that MM-LDL increases cAMP levels both by
      stimulating Gi and inhibiting Gi complexes.

PMID- 7583586
TI  - The interstitium of the human arterial wall contains very large amounts of
      extracellular superoxide dismutase.
AB  - The levels of the secreted, interstitially located extracellular superoxide
      dismutase (EC-SOD), the cytosolic copper-and-zinc-containing SOD (CuZn-SOD), and
      the mitochondrial manganese-containing SOD (Mn-SOD) were measured in the walls of
      human coronary arteries, proximal thoracic aortas, and saphenous veins. The blood
      vessel walls, particularly the arteries, were found to contain exceptionally
      large amounts of EC-SOD, whereas the levels of CuZn-SOD and Mn-SOD were
      relatively low compared with other tissues. Analysis of EC-SOD by
      immunohistochemistry indicates an even distribution in the vessel wall, including
      large amounts of the arterial intima. Arterial smooth muscle cells were found to
      secrete large amounts of EC-SOD and likely are the principal source of the enzyme
      in the vascular wall. The EC-SOD concentration in the human arterial wall
      extracellular space is high enough to efficiently suppress the putative
      pathological effects of the superoxide radical, such as oxidation of LDL and
      reaction with nitric oxide to form the deleterious peroxynitrite. The levels of
      EC-SOD in the aortic wall are found to vary widely among species and were on
      average 6440 U/g in humans, 4340 U/g in the cow, 2660 U/g in the pig, 160 U/g in
      the dog, 770 U/g in the mouse. There were only moderate differences in the
      amounts of CuZn-SOD and Mn-SOD. This wide variation in EC-SOD content suggests
      that the susceptibility to pathologies induced by superoxide radicals in the
      vascular wall interstitium should vary widely among species.

PMID- 7583585
TI  - Differing alpha-tocopherol oxidative lability and ascorbic acid sparing effects
      in buoyant and dense LDL.
AB  - The enhanced oxidizability of smaller, more dense LDL is explained in part by a
      lower content of antioxidants, including ubiquinol-10 and alpha-tocopherol. In
      the present studies, we also observed greater rates of depletion of alpha
      tocopherol (mole per mole LDL per minute) in dense (d = 1,040 to 1,054 g/mL)
      compared with buoyant (d = 1,026 to 1,032 g/mL) LDL in the presence of either
      Cu2+ or the radical-generating agent 2-2'-azobis (2
      amidinopropane)dihydrochloride. Differences were particularly pronounced at the
      lowest Cu2+ concentration tested (0.25 mumol/L), with a fivefold greater rate in
      dense LDL. At higher concentrations (1.0 and 2.5 mumol/L Cu2+), there was a
      greater dependence of depletion rate on initial amount of alpha-tocopherol, which
      was reduced in dense LDL, thus resulting in smaller subfraction-dependent
      differences in depletion rates. Inclusion of ascorbic acid (15 mumol/L), an
      aqueous antioxidant capable of recycling alpha-tocopherol by hydrogen donation,
      was found to extend the course of Cu(2+)-induced alpha-tocopherol depletion in
      both buoyant and dense LDL, but this effect was more pronounced in dense LDL
      (time to half-maximal alpha-tocopherol depletion was extended 15.6-fold and 21.2
      fold in buoyant and dense LDL, respectively, at 2.5 mumol/L Cu2+; P< .05). Thus,
      dense LDL exhibits more rapid alpha-tocopherol depletion and conjugated diene
      formation than buoyant LDL when oxidation is performed in the absence of ascorbic
      acid, but these differences are reversed in the presence of ascorbic
      acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583587
TI  - Human endothelial cell damage by neutrophil-derived cathepsin G. Role of
      cytoskeleton rearrangement and matrix-bound plasminogen activator inhibitor-1.
AB  - Cathepsin G, a major protease released by activated neutrophils, induces
      functional and morphological damage to human endothelial cells. We studied the
      mechanisms involved and ways to reverse this damage. Cathepsin G induced a
      concentration- and time-dependent injury to human umbilical vein endothelial cell
      (HUVEC) morphology simultaneous with cytoskeleton rearrangement. Preincubation of
      the endothelial monolayer with phallacidin completely prevented damage to cell
      morphology by cathepsin g, whereas preincubation with cytochalasin b potentiated
      its activity. Damage to cell shape and F-actin cytoskeleton were prevented by
      eglin C, and inhibitor of the active site of cathepsin G. Furthermore, cathepsin
      G increased transcellular permeability to albumin and induced a time-dependent
      detachment of PAI-1 from the extracellular matrix of a cell-free system. The
      inhibition of matrix-bound PAI-1 activity by specific antibodies induced matrix
      bound PAI-1 activity by specific antibodies induced changes in HUVEC monolayers
      similar to those observed after cathepsin G. However, although stabilization of F
      actin microfilaments by phallacidin prevented changes in cell shape, it did not
      prevent the ability of cathepsin G to increase cell permeability and release
      matrix PAI-1. The damage of cathepsin G to cell morphology and cytoskeleton
      arrangement was reversed within 12 hours if the deendothelialization area was <
      50% to 55% and the subendothelial matrix was still able to bind the newly
      synthesized PAI-1. Thrombin, whose role in the thrombotic process is well known,
      also induced changes in cell morphology and cytoskeleton arrangement of HUVEC.
      Cathepsin G reaches the subendothelial matrix through an increase in cell
      permeability and injures endothelial cell morphology by detaching matrix-bound
      PAI-1. These events expose a highly thrombogenic surface to which platelets can
      adhere, become activated, attract further neutrophils, and trigger thrombus
      formation.

PMID- 7583589
TI  - Thrombin induces the redistribution and acute release of tissue factor pathway
      inhibitor from specific granules within human endothelial cells in culture.
AB  - Tissue factor pathway inhibitor (TFPI) is a vascular anticoagulant that regulates
      the tissue (TF)-dependent pathway of coagulation. The majority of intravascular
      TFPI is thought to be noncovalently bound to the vessel wall. Our
      immunolocalization studies in cultures of human umbilical vein endothelial cells
      (HUVEC) and immortalized EA.hy926 cells that TFPI is located in well-defined
      granules evenly spread over the cell surface and with apical polarization within
      the cytoplasm. These granules are smaller than and distinct from Weibel-Palade
      bodies. Upon treatment of cultured cells with low concentrations of thrombin
      (0.01 to 1 NIH U/mL), a marked redistribution of TFPI, occurred with patching in
      focal points and increased exposure of both TFPI antigen and anticoagulant
      activity on the surface of the stimulated endothelial cells. This redistribution
      was paralleled by an acute release of TFPI in the cell medium. EA.hy926 cells
      responded more readily to thrombin stimulation than HUVECs. The process was
      inhibited by both hirudin and anti-thrombin receptor antibody. Our findings
      demonstrate a novel mechanism by which thrombin may exert a negative feedback
      control on blood coagulation. Therefore, this pathway can be physiological
      importance in controlling TF-mediated thrombin generation.

PMID- 7583588
TI  - Extracellular mast cell granules carry apolipoprotein B-100-containing
      lipoproteins into phagocytes in human arterial intima. Functional coupling of
      exocytosis and phagodytosis in neighboring cells.
AB  - In experimental studies in vitro, mast cells have induced uptake of
      apolipoprotein B-100 (apoB-100)-containing low-density lipoproteins by
      macrophages, with the subsequent formation of foam cells, the hallmarks of
      atherosclerosis. Recently, increased numbers of activated, ie, degranulated, mast
      cells were found to be present in human coronary fatty streaks and atheromas. We
      therefore sought evidence of a connection between mast cells and foam cell
      formation in vivo. In electron microscopic studies of human aortic and coronary
      fatty streaks and atheromas, exocytosed cytoplasmic secretory granules of mast
      cells were detected in the vicinity of their parent cells. These exocytosed
      granules had bound apoB-100-containing lipoproteins, as indicated by their
      positive staining with MB 47, a monoclonal antibody against apoB-100. A smooth
      muscle cell was observed to be in the process of phagocytosing one such
      exocytosed granule, and in the vicinity of a degranulated mast cell a foam cell
      contained an ingested mast cell granule. Therefore, the micrographs show that
      exocytosed granules of intimal mast cells may contribute to intimal foam cell
      formation and suggest a role for mast cells in human atherogenesis. More
      generally, the findings provide evidence that phagocytosis of apoB-100-carrying
      particles is one mechanism by which lipoproteins enter human arterial intimal
      cells.

PMID- 7583590
TI  - Role of nitric oxide in hemostatic system activation in vivo in humans.
AB  - NO is a potent inhibitor of in vitro platelet aggregation and adhesion. In view
      of possible future widespread use of NO in pulmonary and cardiovascular diseases,
      we investigated the role of NO in hemostatic system activation in vivo in humans.
      Sixteen healthy male volunteers (age range, 22 to 33 years) received either NO by
      inhalation (50 ppm over 30 minutes; n = 8) or the NO synthase inhibitor NG
      monomethyl L-arginine (L-NMMA 3mg/kg body weight i.v. over 5 minutes; n = 8),
      beta-Thromboglobulin (beta-TG), an indicator of platelet activity; prothrombin
      fragment 1 + 2 (F 1 + 2), an index of coagulation activation; and thromboxane B2
      (TxB2), a measure of platelet prostaglandin synthesis, were determined in blood
      samples obtained from bleeding-time incisions ("shed blood") at baseline and
      after administration of the respective drug. In addition, beta-TG and F 1 + 2
      were also determined in venous blood. To verify the systemic effects of the
      drugs, methemoglobin and plasma nitrites/nitrates were measured in the NO group,
      and cardiac output and exhaled NO were measured in the L-NMMA group. Compared
      with baseline, methemoglobin and plasma nitrates increased by 73 +/- 12% (P=
      .006) and 60 +/- 9% (P< .001), respectively, following NO inhalation. L-NMMA
      infusion resulted in decreases in both cardiac output by 16 +/- 2%; P< .001) and
      exhaled NO (by 54 +/- 7%; P< .001). NO inhalation or L-NMMA infusion had no
      significant effect on beta-TG, F 1 + 2, and TxB2 levels in shed blood.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7583591
TI  - Inhibition of nitric oxide biosynthesis promotes P-selectin expression in
      platelets. Role of protein kinase C.
AB  - Inhibition of NO synthesis promotes P-selectin expression on endothelial cells;
      however, the precise mechanism is unclear. Because No has been shown to inhibit
      protein kinase C (PKC) activity, we examined the hypothesis that the NO synthase
      inhibitor NG-nitro-L-arginine methyl ester (L-NAME) stimulates P-selectin
      expression on platelets via PKC activation. Ten-minute incubation with either
      phorbol 12-myristate 13-acetate (PMA), thrombin, or L-NAME significantly
      increased P-selectin expression on platelets (as assessed by flow-cytometric
      analysis) and PKC activity of platelet membranes. Increased P-selectin expression
      induced by either PMA, thrombin, or L-NAME was significantly attenuated by the
      selective PKC inhibitor UCN-01 (7-hydroxystaurosporine). Furthermore, L-NAME
      induced P-selectin expression was significantly attenuated by either L-arginine,
      8-bromo-cGMP, or sodium nitroprusside (SNP). Interestingly, L-NAME further
      potentiated P-selectin upregulation by thrombin. L-NAME, thrombin, and PMA also
      significantly increased polymorphonuclear leukocyte adherence to the coronary
      artery endothelium, an effect that was significantly attenuated by the anti-P
      selectin monoclonal antibody PB1.3 or by UCN-01, L-arginine, 8-bromo-cGMP or SNP
      but not by D-arginine or he nonblocking anti-P-selectin monoclonal antibody
      NBP1.6. These results indicate that inhibition of NO synthesis induces rapid P
      selectin expression, which appears to be at least partially mediated by PKC
      activation in platelets. Similar effects and mechanisms of L-NAME on P-selectin
      function were also observed in endothelial cells, another site of P-selectin
      expression.

PMID- 7583593
TI  - The American Federation for Clinical Research, Midwest section, annual meeting.
      Chicago, Illinois, September 28-30, 1995. Abstracts.

PMID- 7583592
TI  - Oxidized low-density lipoproteins facilitate leukocyte adhesion to aortic intima
      without affecting endothelium-dependent relaxation. Role of P-selectin.
AB  - Inflammatory cell deposition in atherosclerotic blood vessels has been thought to
      relate to loss of endothelium-derived nitric oxide (NO). To examine whether cell
      deposition correlates temporally with the loss of NO activity, rat aortic rings
      were incubated with buffer, native LDL (n-LDL), oxidized LDL (ox-LDL), or the
      endothelium-derived relaxing factor synthase inhibitor N omega-nitro-L-arginine
      methyl ester (L-NAME) for 2 hours, and vascular contractile response to
      norepinephrine and relaxant response to acetylcholine, thrombin, and calcium
      ionophore A23,187 were examined. Thereafter, the rings were exposed to biotin
      fluorescein isothiocyanate-labeled fluorescent or unlabeled leukocytes for 30
      minutes. Cell adhesion was quantitated by fluorescent microscopy as well as by
      scanning electron microscopy. Incubation with n-LDL or ox-LDL did not affect
      either the contractile or the relaxant response of rings. However, leukocyte
      adhesion increased markedly in all ox-LDL-treated rings but not in those treated
      with n-LDL. Thus, leukocyte adhesion occurred independent of NO activity. In
      keeping with this concept, pretreatment of rings with the NO precursor L-arginine
      failed to influence leukocyte adhesion to rings incubated with ox-LDL. Treatment
      of rings with L-NAME also resulted in adhesion of a large number of leukocytes.
      Furthermore, all rings treated with ox-LDL or L-NAME demonstrated marked
      expression of P-selectin leukocyte adhesion molecules, determined by
      immunohistochemistry. Pretreatment of rings with the P-selectin blocking antibody
      PB1.3 markedly decreased deposition of leukocytes in rings exposed to ox
      LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583594
TI  - Mitochondrial very long chain acyl-CoA dehydrogenase deficiency--a new disorder
      of fatty acid oxidation.
AB  - Very long chain acyl-CoA dehydrogenase is a newly characterised enzyme in
      mitochondrial fatty acid oxidation. A girl who presented on the second day of
      life with a sudden and severe illness due to deficiency of this enzyme is
      reported. There is evidence that some children (and perhaps all) originally
      diagnosed with a deficiency of long-chain acyl-CoA dehydrogenase, in fact, have a
      defect involving very long chain acyl-CoA dehydrogenase.

PMID- 7583595
TI  - Model to identify potentially preventable cerebral palsy of intrapartum origin.
AB  - A six stage model was applied to a geographically defined population of 210
      singleton children born at term who had a diagnosis of cerebral palsy at 5 years
      of age. Thirty five children were identified as those most likely to have
      cerebral palsy of intrapartum origin; in 26 of these there was evidence of
      suboptimal care. It is suggested that this simple model should be tested on
      populations of children with cerebral palsy and the underlying principles used
      when considering the likely cause of cerebral palsy in individual children.

PMID- 7583596
TI  - Failure of the urinary group B streptococcal antigen test as a screen for
      neonatal sepsis.
AB  - The accuracy of the urinary group B streptococcal antigen latex agglutination
      (LA) test for screening infants at risk of group B streptococcal (GBS) sepsis in
      the first 24 hours of life was prospectively studied in 236 infants for six
      months. Infection with GBS was defined by a positive blood culture while
      colonisation was defined by GBS cultured from any other site. The combination of
      infection and colonisation was used as the gold standard for the LA test.
      Although the LA test had a sensitivity of 90%, the specificity was only 70%, the
      positive predictive value 12% and the false positive rate 30%. The overall
      accuracy was only 71%. The LA test was unable to predict GBS sepsis in infants at
      risk of the disease. The false positive rate was unacceptably high and could not
      be potentially accounted for in 11 infants. However, a negative test was useful
      in excluding GBS disease.

PMID- 7583600
TI  - Raised cerebral artery blood flow velocity.

PMID- 7583598
TI  - Dr Francis Ramsbotham (1801-1868) and obstetric practice in London.

PMID- 7583601
TI  - Neonatal abstinence syndrome.

PMID- 7583599
TI  - Need to avoid bias in controlled trials.

PMID- 7583602
TI  - Pros and cons of antiseptic cord care.

PMID- 7583597
TI  - Antioxidants in neonatal lung disease.

PMID- 7583603
TI  - Cardiac arrest associated with vancomycin in a neonate.

PMID- 7583604
TI  - Guidance after twin and singleton death.

PMID- 7583606
TI  - Predictors for mortality.

PMID- 7583605
TI  - Intestinal dilatation in the fetus.

PMID- 7583607
TI  - Neural migration disorders studied by cerebral ultrasound and colour Doppler flow
      imaging.
AB  - Cerebral ultrasound and colour Doppler flow imaging (CDFI) were used to diagnose
      a wide spectrum of anomalies of cell migration (17 patients): presumed
      lissencephaly (n = 12); schizencephaly of both fused (n = 2) and open lips (n =
      2); hemimegalencephaly (n = 1); and subependymal type grey matter heterotopia (n
      = 12). The patients with grey matter heterotopia had irregular ventricular
      margins (n = 10), periventricular hyperechogenic bands (n = 12), and/or
      periventricular hyperechogenic nodules (n = 7). Some patients had more than one
      type of migration disorder as well as other central nervous system malformations.
      Cerebral ultrasound diagnoses were confirmed by magnetic resonance imaging (MRI)
      or necropsy. It is concluded that colour Doppler flow imaging is a worthwhile
      addition to the assessment of brain surface anomalies.

PMID- 7583608
TI  - Motor impairment in children 12 to 13 years old with a birthweight of less than
      1250 g.
AB  - AIM: To determine whether poor motor skills, previously identified in a cohort of
      very low birthweight (< 1250 g) children, born in 1980-1, have persisted or
      improved. Previous assessments had shown significant improvement between the ages
      of 6 and 8 years. METHODS: The original cohort were traced and were assessed
      using the Movement Assessment Battery for Children, an update of the Test Of
      Motor Impairment, used at 6 and 8 years. Where possible the classroom-matched
      controls from the original studies were assessed, otherwise new controls were
      selected. Teachers were also asked to identify those children whom they
      considered clumsy. Forty seven of the original cohort of 53 children, all but one
      still attending mainstream school, and 40 original and 20 new classroom-matched
      controls were studied. RESULTS: Fifty one per cent of the cohort showed
      clinically important or borderline impairment. More of these children had
      significant impairment (16/47, 34%) than the controls (3/60, 5%). The improvement
      seen by 8 years of age was maintained but there was no further improvement. Girls
      had significantly higher overall impairment scores (median 16; interquartile
      range 10-21.5) than the boys (5.5 (1.5-12.5)), and on a wider variety of subtests
      (5/8) than the boys (3/8). CONCLUSIONS: Many very low birthweight children have
      impaired motor skills. Despite early improvement it persists into adolescence and
      the deficit remains. Interventional studies may help to see if these problems can
      be alleviated.

PMID- 7583610
TI  - Predictive value of early neuroimaging, pulsed Doppler and neurophysiology in
      full term infants with hypoxic-ischaemic encephalopathy.
AB  - To evaluate their prognostic value, five different non-invasive techniques were
      used on 34 full term infants with hypoxic-ischaemic encephalopathy (HIE) within
      six hours of delivery. Cranial ultrasonography, the resistance index (RI) of the
      middle cerebral artery obtained with Doppler ultrasonography, somatosensory
      evoked potentials (SEPs), visual evoked potentials (VEPs) and the cerebral
      function monitor (CFM) were used. According to the criteria of Sarnat, 11 infants
      developed mild, seven moderate, and 16 severe encephalopathy. The CFM had the
      highest positive (PPV 84.2%) and negative predictive value (NPV 91.7%). All but
      one of the infants with a continuous pattern had a good outcome. The CFM of 11
      cases with a suppression-burst pattern changed to a continuous pattern over 24 to
      48 hours in four infants, and was associated with a normal outcome in three. All
      five cases with an isoelectric CFM died. The SEPs also provided useful
      information (PPV 81.8%; NPV 91.7%). VEPs were often delayed during the first
      hours or life and did not carry a poor prognosis in five of 14 cases (PPV 77.3%).
      Both ultrasonography and Doppler RI were of little value, as they were almost
      always normal at this early stage. In 34 full term infants with HIE, studied
      within 6 hours of life, the CFM and SEPs provided the most useful information
      about the expected course of encephalopathy and subsequent neurodevelopmental
      outcome.

PMID- 7583609
TI  - Ischaemic and haemorrhagic brain lesions in newborns with seizures and normal
      Apgar scores.
AB  - Serial ultrasound scans and conventional and diffusion weighted magnetic
      resonance imaging (MRI) were performed on 16 neonates who presented with
      seizures. The Apgar scores were normal and subsequently no metabolic or infective
      cause could be found. The aim of the study was to evaluate the extent to which
      early sequential imaging can elucidate the cause of seizures in apparently
      neurologically normal infants. Fourteen of the infants had haemorrhagic or
      ischaemic lesions on MRI and these were detected by ultrasound scanning in 11.
      Early ultrasound scanning detected the haemorrhagic lesions but the ischaemic
      lesions were often not seen until the end of the first week of life. Early MRI,
      however, was able to detect all the ischaemic lesions. The evolution of the
      insult could be timed by using serial ultrasound scans and a combination of
      diffusion weighted and conventional MRI during the first week of life, confirming
      a perinatal insult even in the absence of fetal distress. Although the aetiology
      of these lesions remains obscure, serial ultrasound scans will detect the
      presence of cerebral lesions in neonates presenting with isolated seizures but
      additional MRI sequences will give better definition on type, site, and extent of
      the pathology.

PMID- 7583611
TI  - Oxygen at birth and prolonged cerebral vasoconstriction in preterm infants.
AB  - To determine if the use of oxygen in the delivery room influences subsequent
      global cerebral blood flow (CBF), 70 infants of gestational age of less than 33
      completed weeks were randomly assigned to receive room air (group I) or 80%
      oxygen (group II) during the initial stabilisation at birth. In group I
      supplemental oxygen was administered on clinical indications, when required.
      After being admitted to the neonatal intensive care unit all infants were treated
      according to our normal practice. At a postnatal age of 2 hours CBF was measured
      by xenon clearance. Seventy four per cent of the infants in group I were
      successfully stabilised without the need for supplemental oxygen. CBF was
      significantly higher in group I than in group II (CBF median (interquartile
      range): 15.9 (13.6-21.9) v 12.2 (10.7-13.8) ml/100 g/minute). Differences in
      oxygen exposure seemed to be the only explanation for the differences in CBF. No
      differences in short term outcome were found between the groups.

PMID- 7583612
TI  - Third trimester fetal growth and umbilical venous blood concentrations of IGF-1,
      IGFBP-1, and growth hormone at term.
AB  - Insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein
      1 (IGFBP-1) and growth hormone (GH) concentrations were measured in umbilical
      venous blood after delivery of 78 term newborn infants. Three groups of
      pregnancies were prospectively identified during the third trimester, according
      to fetal size and subsequent fetal growth, assessed by repeated ultrasound scans.
      Fetal size was considered either appropriate for gestational age (AGA) or small
      for gestational age (SGA), according to whether the first ultrasound measurement
      of abdominal circumference was equal to or above, or below the tenth centile for
      gestational age, respectively. Subsequent fetal growth was quantified by the
      change in the standard deviation score of abdominal circumference measurements
      between the first and last scans before delivery. Fetal growth retardation (FGR)
      was defined as a (negative) change in SD score of greater than -1.5. Eighteen SGA
      fetuses with evidence of FGR had significantly lower IGF-1 (median 0.05 (range
      0.0-0.24) U/ml) at delivery than 35 SGA fetuses with normal growth (median 0.13
      (range 0.0-0.94) U/ml; P < 0.05) and 25 AGA fetuses with normal growth (median
      0.31 (range 0.0-0.84) U/ml; P < 0.05). The median concentration in the SGA group
      with normal growth was also significantly lower than that of the AGA group with
      normal growth. There were no significant differences in IGFBP-1 or GH
      concentrations between the three groups. These observations indicate that
      umbilical blood concentrations at birth of IGF-1, but not IGFBP-1 or GH, relate
      to both fetal size and fetal growth during the third trimester of pregnancies
      reaching term.

PMID- 7583613
TI  - Role of ECMO in the treatment of respiratory syncytial virus bronchiolitis: a
      collaborative report.
AB  - AIM: To report the collaborative experience of extracorporeal membrane
      oxygenation (ECMO) in the treatment of respiratory syncytial virus (RSV)
      bronchiolitis between April 1989 and January 1995. METHODS: The medical records
      of patients with confirmed RSV bronchiolitis referred to three centres
      (Leicester, Glasgow, and Great Ormond Street) were reviewed. RESULTS: Twenty four
      infants were identified. Seventeen had been born prematurely (gestational range
      23-40 weeks, median 30 weeks). Thirteen infants had been mechanically ventilated
      after birth and seven of these had evidence of bronchopulmonary dysplasia (BPD).
      The age of onset of RSV infection varied from three to 64 weeks (mean 17.4 weeks,
      median 12 weeks). Ventilation before ECMO ranged from one to 16 days and
      oxygenation indices at the time of referral ranged from 21-73 (mean 39).
      Ribavirin was used in eight of the 24 patients. Sixteen patients received
      venoarterial and eight veno-venous ECMO. ECMO hours ranged from 32-647 (median
      196 hours). One infant died (survival rate 96%). Cranial ultrasound abnormalities
      were detected in three patients. However, at follow up only one of the 23
      survivors had evidence of developmental delay. CONCLUSION: A group of paediatric
      patients in whom ECMO can be of benefit has been identified. The use of ECMO
      should be considered when other means of support prove unsuccessful.

PMID- 7583614
TI  - Pulmonary haemodynamics after surfactant replacement in severe neonatal
      respiratory distress syndrome.
AB  - Aortopulmonary pressure difference and pulmonary blood flow velocity were studied
      during the first 48 hours of life in 12 premature neonates with severe
      respiratory distress syndrome (RDS), treated by natural surfactant, and in 25
      premature neonates with mild RDS. A non-invasive Doppler ultrasound method was
      used to estimate aortopulmonary pressure difference and pulmonary blood flow
      velocity from the left pulmonary artery. Aortopulmonary pressure difference was
      significantly lower at 6 hours of age in the infants with severe RDS and was not
      increased one hour after surfactant therapy. Aortopulmonary gradient started to
      rise at 24 hours of age and was equal to that of neonates with mild RDS at 48
      hours. Pulmonary blood flow velocity was significantly lower, initially in the
      severe RDS group, and was not increased one hour after surfactant therapy. Left
      pulmonary artery flow velocity began to rise after 24 hours and reached the
      values of the mild RDS group at 48 hours. These data indicate that aortopulmonary
      pressure difference and pulmonary blood flow are low in the acute phase of RDS
      and that surfactant treatment does not seem to affect these values.

PMID- 7583616
TI  - Structural brain imaging in schizophrenia.
AB  - In vivo neuroimaging techniques have characterized the global features of brain
      dysmorphology in schizophrenia. These features include ventriculomegaly and
      widespread sulcal dilation, which particularly affect the frontal and temporal
      lobes and involve cortical gray matter rather than white matter. Dysmorphology of
      specific brain structures such as the basal ganglia and hippocampus, which have
      been implicated in the pathophysiology of schizophrenia by pharmacological
      manipulations and post mortem investigations, have not been consistently observed
      in vivo, perhaps because of differences in imaging and analysis techniques,
      methods used to control for variance due to age and head size, and sample
      characteristics. The epidemiology of the observed widespread brain dysmorphology
      supports a developmental origin, perhaps with limited progressive change beyond
      that expected in normal aging. Establishing the clinical significance of
      relatively static structural brain dysmorphologies remains a major challenge that
      may be best met by use of combined cross-sectional and longitudinal study
      designs.

PMID- 7583617
TI  - Utilization of radioligands in schizophrenia research.
AB  - Interest in the role of monoaminergic mechanisms in schizophrenia has stimulated
      the development of specific radioligands that allow PET analysis of quantitative
      aspects of monoamine receptor subtypes in the living human brain. Clinical
      studies with such ligands have not consistently demonstrated specific alterations
      of the total populations of D1 and D2 dopamine receptors in the caudate putamen
      complex of drug-naive schizophrenic patients. However, recent studies using
      [11C]SCH 23390, a specific D1 dopamine receptor ligand, disclosed a highly
      significant reduction of ligand binding in pixel elements of the basal ganglia
      that normally contain high activity. This finding may be related to reduced D1
      dopamine regulated transmission in subsets of neuronal pathways within the basal
      ganglia. D3, D4, and D5 receptor subtypes constitute minor fractions of the total
      number of dopamine receptors in the human brain. However, efforts to find
      selective ligands for D3 and D4 subtypes also show promise. Radioligands for
      monoamine receptors have also been used to follow drug effects on receptor
      subtypes in schizophrenic patients treated with different types of antipsychotic
      drugs. Such studies have allowed the analysis of relationships between occupancy
      of dopamine receptor subtypes and some clinical manifestations of drug treatment.
      Such studies with the selective D2 antagonist raclopride indicated quantitative
      relationships between the degree of D2 dopamine receptor occupancy in the basal
      ganglia and the extrapyramidal manifestations, as well as the antipsychotic
      action. Some of the currently available antipsychotic drugs also induced
      significant occupancy of D1 dopamine receptors. However, the selective D1
      antagonist SCH 39166 in doses inducing a more than 70% occupancy of D1 dopamine
      receptors in the caudate putamen failed to induce an antipsychotic action. This
      indicates that, in contrast to D2 blockade, selective antagonism of D1-regulated
      pathways does not mediate antipsychotic action in schizophrenia. Some but not all
      antipsychotic drugs also induced high occupancy of neocortical 5HT2A receptors.
      Because selective 5HT2A antagonism does not appear to be an efficient treatment
      for schizophrenia, it seems most likely that 5HT2A receptors and, perhaps, D1
      receptors act in concert to modify aspects of the mandatory D2 blockade to induce
      antipsychotic actions. Computer graphic methods for image analysis add new
      dimensions to brain imaging research, allowing three-dimensional visualization of
      receptor populations computed from molecular PET data. This will make possible
      further exploration of the detailed molecular compartmentalization of the human
      brain using radioligand binding.

PMID- 7583615
TI  - Effect of human colostrum on interleukin-2 production and natural killer cell
      activity.
AB  - The effect of human colostrum on the production of interleukin-2 (IL-2) and on
      natural killer (NK) cell activity by peripheral blood mononuclear cells (PBMC)
      was investigated in 50 healthy women. At concentrations as low as 0.5%, human
      colostrum stimulated IL-2 production; at a higher concentration (10%), IL-2
      secretion was inhibited. A time and dose dependent inhibitory effect of colostrum
      on NK cytotoxicity was also observed. This inhibition could be reversed by the
      addition of human recombinant IL-2 (hrIL-2). The stimulation of IL-2 production
      induced by human colostrum might compensate for its inhibitory effect on NK cell
      activity. These findings suggest an additional mechanism by which breast feeding
      may affect the neonatal immune system.

PMID- 7583618
TI  - Positron emission tomography studies of abnormal glucose metabolism in
      schizophrenic illness.
AB  - Advances in psychopharmacology and neuroscience have brought into view a wide
      field of competing mechanisms for the etiology of schizophrenia including, but
      not limited to, deficits in one or more neurotransmitters (dopamine, serotonin,
      GABA, glutamate, and noradrenaline systems), neurodevelopmental defects in
      cortical connectivity, and viral infection. Genetic studies suggest heterogeneity
      in the illness, with multifactorial inheritance. Since cerebral metabolic
      activity reflects regional brain work for all neurotransmitter systems, imaging
      studies can provide information on the functional neuroanatomy of a deficit in
      the individual patient, allowing the grouping of patients for more intensive
      investigation in more homogeneous groups. Metabolic imaging studies allow
      psychopharmacological response to be regionally assessed and clinical responders
      to be identified, even for medications that affect more than one neurotransmitter
      system or have clinical effects that derive from changes in activity one synapse
      or more removed from the site of primary action.

PMID- 7583619
TI  - Gating and habituation deficits in the schizophrenia disorders.
AB  - Gating and habituation deficits have been identified as major features of the
      schizophrenias. When gating and habituation functions are impaired, the
      schizophrenia patient can neither efficiently screen out trivial, distracting
      stimuli nor effectively attend to and process salient stimuli in the environment.
      Along with the clinical significance and symptom correlates of gating and
      habituation deficits in schizophrenia, studies of these functions have produced
      much important data. Specifically, such studies have demonstrated the involvement
      of structures in the cortico-striato-pallido-pontine (CSPP) neural circuitry in
      both schizophrenia and the normal processing of information. Thus,
      neurobiological manipulations along various axes of the CSPP can allow
      investigators to understand the neural basis of impaired gating and habituation
      in the schizophrenias.

PMID- 7583620
TI  - New diagnostic issues in schizophrenic disorders.
AB  - The evolution of our understanding of schizophrenia has provided new concepts
      that substantially alter answers to questions such as age of onset, distribution
      by sex, and treatment response. Moreover, these new concepts offer heuristic
      advantages in etiopathophysiological study designs and permit investigators to
      address key sources of artifact. We discuss the unitary versus the clinical
      syndromal concept of schizophrenia and describe the implications of the latter
      with regard to the study of schizophrenia. We also present a heuristic tripartite
      division of schizophrenic symptoms for reducing syndromal heterogeneity.

PMID- 7583621
TI  - Role of serotonin in the action of atypical antipsychotic drugs.
AB  - Clozapine is the first of a new generation of antipsychotic drugs which
      constitutes a major advance in the treatment of schizophrenia. Numerous theories
      have been proposed to explain the advantages of clozapine over typical
      neuroleptics. Most of these focus on its effects on dopaminergic and serotonergic
      neurotransmission. This article reviews the effects of clozapine and related
      antipsychotic drugs on dopamine (DA) D1, D2, and D4, and serotonin (5-HT) 5-HT2A,
      5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors, as well as its ability to modulate DA
      and 5-HT release. Clozapine and other atypical antipsychotic drugs share the
      ability to cause fewer extrapyramidal symptoms at clinically effective doses.
      This may be related to their potent 5-HT2A and weak D2 receptor blocking
      properties, a profile shared by risperidone, melperone, olanzapine, amperozide,
      HP-873, seroquel, sertindole, and ziprasidone. The basis for the superior ability
      of clozapine to treat negative symptoms and enhance cognitive function compared
      to typical neuroleptic drugs in schizophrenic patients has not yet been
      ascertained, but there is evidence that its effect on 5-HT2A, D2, or D4 receptors
      may be important. Other aspects of the pharmacology of clozapine which may
      contribute to its actions include potent alpha 1-adrenergic, M1, M2, M3, and M5
      receptor blocking properties, as well as M4 agonist effects.

PMID- 7583622
TI  - Genetic anticipation in schizophrenia: pro and con.
AB  - Recently, it has been demonstrated that unstable trinucleotide repeats are the
      etiologic factor in myotonic dystrophy, fragile-X syndrome, Kennedy's disease,
      Huntington's disease, spinocerebellar ataxia type 1, and dentatorubral
      pallidoluysian atrophy. All available evidence suggests that these expanded
      trinucleotide repeats, or unstable DNA, are the biological basis of the clinical
      phenomenon of genetic anticipation. Two components of anticipation, increased
      severity and earlier age of onset in subsequent generations, have been widely
      observed in schizophrenia. We review the evidence for and against genetic
      anticipation in schizophrenia. Although the major criticisms of the anticipation
      hypothesis can be questioned, so can the evidence in favor of it. We conclude
      that molecular genetic approaches might be the most useful means of resolving
      ambiguity in clinical arguments about the origin of the anticipation-like
      phenomenon in schizophrenia.

PMID- 7583623
TI  - New morphological and neuropathological findings in schizophrenia: a
      neurodevelopmental perspective.
AB  - This article reviews evidence for morphological abnormalities in schizophrenia as
      assessed by brain imaging and neurohistochemical techniques including
      immunohistochemistry and in situ hybridization. Localized deficits in
      schizophrenic brain appear in many regions including frontal and temporal lobes,
      anterior cingulate, mediodorsal thalamic nucleus, and corpus callosum. These
      areas are interconnected and may provide the basis for a "psychosis circuitry."
      Neuronal disruption of elements in this circuitry may result in a hypothesized
      dysconnection syndrome. Evidence suggests an alteration in neuronal development
      related to either genetic and/or environmental factors. Primary and secondary
      anterograde and retrograde effects may accompany this neurodevelopmental defect
      and may further alter intrinsic and extrinsic neuronal communications. A number
      of studies are consistent with the second trimester of gestation being a critical
      period for fetal brain development, especially for neuronal migration. Fetal
      trauma due to environmental insults (e.g., influenza) during this trimester may
      increase the incidence of schizophrenia. Recent advances in the identification of
      factors that modulate neuronal development including axon guidance molecules,
      neurotrophins, and programmed cell death genes provide intriguing new areas for
      potential investigation. Future research may focus on the factors controlling
      neuronal migration and programmed cell death in the schizophrenic brain.

PMID- 7583624
TI  - Schizophrenia: a disconnection syndrome?
AB  - We review the evidence of pathophysiological changes in the prefrontal and
      temporal cortices of schizophrenic subjects and of abnormal integration of the
      physiological dynamics in these two regions. The argument we develop is that some
      schizophrenic phenomena are best understood in terms of abnormal interactions
      between different areas, not only at the levels of physiology and functional
      anatomy, but at the level of cognitive and sensorimotor functioning. We discuss
      recent functional imaging evidence suggesting abnormal prefronto-temporal
      interactions in relation to a psychological analysis of experiential symptoms in
      schizophrenia. Cortico-cortical interactions have been assessed in terms of
      functional connectivity and eigenimages, using time series of neurophysiological
      data obtained with positron emission tomography. The results of these analyses
      suggest that there is a profound disruption of large-scale prefronto-temporal
      interactions in schizophrenia. These disruptions are particularly relevant if one
      considers that many positive symptoms of schizophrenia reflect a failure to
      integrate intrinsically generated behaviour and concurrent perception.

PMID- 7583625
TI  - Neurodevelopmental animal models of schizophrenia.
AB  - One difficulty in reproducing the core neurobiological features of schizophrenia
      in experimental animals is that most neurobiological data about the illness are
      inclusive: neither the inducing conditions nor the neurobiological mechanisms
      have been made clear. We review the advantages and limitations of animal models
      of schizophrenia based on neurodevelopmental hypotheses that implicate early,
      probably prenatal age, as the time at which the fundamental disease process
      occurs. These models, although principally founded on circumstantial clinical
      evidence of early developmental neuropathology, seem to reproduce a surprisingly
      broad spectrum of prominent neurobiological aspects of the disorder, and may help
      explain mechanisms that underlie the pathophysiology of this illness. In
      particular, the model based on neonatal excitotoxic hippocampal damage has
      provided data indicating the neurobiological plausibility of the notion that a
      developmental cortical defect has a delayed effect on cortical function and
      dopamine regulation (i.e., the neurodevelopmental hypothesis).

PMID- 7583626
TI  - New crystal structures of nucleic acids and their complexes.
AB  - In the past year, X-ray crystallographic studies of representatives of all
      nucleic acid structural types have been reported. Among the most interesting
      structures are the parallel DNA tetraplex formed by d(TGGGGT), the four-stranded
      structure formed by d(CCCT) and a double drug bound side by side in an
      antiparallel orientation to the minor groove of a B-DNA. Certainly, the structure
      that has received most attention is that of the first complex of a ribozyme with
      an inhibitor DNA.

PMID- 7583627
TI  - RNA cleavage by small catalytic RNAs.
AB  - Recent studies of the hammerhead ribozyme have provided an insight into its three
      dimensional structure. In addition, studies using chemical probes, functional
      group modification and mutational analysis, in combination with computer
      modelling, have led to proposals for the structure of both the hairpin and
      hepatitis delta virus ribozymes. Such structural elucidations will aid
      understanding of the mechanism of ribozyme catalysis. The discovery that certain
      RNA-binding proteins can increase the catalytic efficiency of ribozymes in
      encouraging for their use in the inhibition of gene expression in vivo.

PMID- 7583628
TI  - RNA folding.
AB  - The number of known motifs for RNA folding and RNA tertiary organization is
      expanding rapidly as we learn more about the diverse biological functions of RNA.
      Problems in protein and RNA folding have melded in recent investigations of
      ribonucleoprotein folding. Theoretical and experimental models are rapidly being
      developed for the pathways and stabilizing forces involved in RNA folding.

PMID- 7583629
TI  - Telomere structure and function.
AB  - Telomeres, the termini of linear eukaryotic chromosomes, contain specific DNA
      sequences that are widely conserved. These sequences not only recruit telomere
      specific proteins, but also give telomeric DNA the ability to fold into four
      stranded DNA structures. Recent structural studies have shown that the repertoire
      of quadruplexes formed by the G-rich strand is larger than had been envisaged.
      Even more surprising is a novel four-stranded structure formed by the C-rich
      strand, called the i-tetraplex. Genetic and biochemical analyses have been used
      to identify proteins involved in telomeric DNA packaging and organization. The
      possibility that four-stranded structures may play a role in telomere function
      has been strengthened by the discovery that telomeric proteins can bind to and
      promote the formation of G-quadruplexes.

PMID- 7583630
TI  - Salt effects on nucleic acids.
AB  - Salt-dependent electrostatic effects are a major factor in determining the
      stability, structure, reactivity, and binding behavior of nucleic acids.
      Increasingly detailed theoretical methods, especially those based on Monte Carlo
      and Poisson-Boltzmann methodologies, combined with powerful computational
      algorithms are being used to examine how the shape, charge distribution and
      dielectric properties of the molecules affect the ion distribution in the
      surrounding aqueous solution, and how they play a role in ligand binding,
      structural transitions and other biologically important reactions. These studies
      indicate that inclusion of detailed structural information about the nucleic acid
      and its ligands is crucial for improving models of nucleic acid electrostatics,
      and that better treatment of the ion atmosphere and dielectric effects is also of
      major importance.

PMID- 7583631
TI  - Hydration and solution structure of nucleic acids.
AB  - Of particular interest among the revelations from recent new DNA structures is
      the finding that both strands of the repeated DNA sequences found in telomeres
      and centromeres may adopt alternative conformations. High-definition NMR studies
      yielded information on the residence time of the water molecules interacting with
      nucleic acids. A better knowledge of the residence time of the hydration water
      may be useful in assessing its contribution to nucleic acid structure.

PMID- 7583633
TI  - Backbone modifications in oligonucleotides and peptide nucleic acid systems.
AB  - In the past year major advances have been made in the design, synthesis and
      characterization of two classes of modified oligonucleotides. In the first class,
      the phosphodiester backbone of 2'-deoxyribo-oligonucleotides has been replaced in
      several different ways. The second group represents a completely different type
      of oligonucleotide modification in which the backbone and the 2'-deoxyribose
      moieties are replaced by amino acids. These advances present new possibilities
      for the pharmaceutical applications of modified oligonucleotides in antisense
      strategies.

PMID- 7583632
TI  - The thermodynamics of DNA structures that contain lesions or guanine tetrads.
AB  - It is becoming increasingly apparent that energetic as well as structural
      information is required to develop a complete appreciation of the critical
      interrelationships between structure, energetics, and biological function.
      Motivated by this recognition, we have reviewed in this article the current state
      of the thermodynamic databases associated with lesion-containing DNA duplexes and
      DNA quadruplexes, while highlighting important considerations concerning the
      methods used to obtain the requisite data.

PMID- 7583635
TI  - Protein secondary structure prediction.
AB  - The past year has seen a consolidation of protein secondary structure prediction
      methods. The advantages of prediction from an aligned family of proteins have
      been highlighted by several accurate predictions made 'blind', before any X-ray
      or NMR structure was known for the family. New techniques that apply machine
      learning and discriminant analysis show promise as alternatives to neural
      networks.

PMID- 7583634
TI  - Statistical significance of sequence patterns in proteins.
AB  - I discuss three recent developments in sequence analysis by the statistical
      method of scores. First is the identification of segments of high aggregate score
      in a single protein sequence. Charge clusters and hyper-charge runs are prime
      examples. Proteins containing hyper-charge runs are principally associated with
      DNA and RNA processing, chromatin structure, ion storage and exchange, and
      protein complex assembly. Second is the protein sequence comparisons identifying
      common segments having high total similarity scores. These are illustrated by
      comparisons within the family of prokaryotic heat shock 70 kDa proteins. Third is
      the scoring protocols applied to the inverse folding problem.

PMID- 7583636
TI  - Seeking significance in three-dimensional protein structure comparisons.
AB  - What is the significance of three-dimensional structural similarity? This
      fundamental question still remains unanswered in spite of advances in automatic
      structure comparison methods that have been made in the last few years. The
      answer to this question will give us a much deeper insight into the principles of
      protein architecture.

PMID- 7583637
TI  - Structural features of a superfamily of zinc-endopeptidases: the metzincins.
AB  - A large number of zinc endopeptidases contain an HEXXHXXGXXH consensus motif in
      their catalytic site (single letter code; X is any amino acid residue). These
      enzymes can be grouped into four distinct families, the astacins, the
      adamalysins, the serralysins and the matrix metalloproteinases (matrixins).
      Despite a low degree of sequence similarity, their catalytic modules are
      topologically similar. A topology derived sequence alignment suggests that the
      four families form a superfamily, called the metzincins because of a perfectly
      superimposable methionine residue close to the zinc-binding active site.
      Topological similarity to the thermolysin-like enzymes indicates that these
      enzymes may have had a common ancestor.

PMID- 7583638
TI  - Cystine knots.
AB  - Recent reports of the crystal structure of the glycoprotein hormone human
      chorionic gonadotrophin show that cystine knots are proving to be versatile
      structural motifs that enable the construction of a variety of proteins with
      different functional properties. Because of their shape, there appears to be an
      intrinsic requirement for the cystine-knot growth factors to form dimers. This
      extra level of organization increases the variety of structures built around this
      simple structural motif.

PMID- 7583640
TI  - Pleckstrin homology domains: a fact file.
AB  - Structures of three different pleckstrin homology domains have been determined
      within the past year. They have a common core consisting of a seven-stranded and
      strongly bent beta-sheet and a C-terminal alpha-helix that packs against the beta
      sheet. Phosphatidylinositol 4,5-bisphosphate and related compounds specifically
      bind to pleckstrin homology domains, suggesting that the domain may be involved
      in reversible anchorage to membranes or in recognition of a second messenger,
      such as inositol 1,4,5-trisphosphate. Pleckstrin homology domains have also been
      suggested to bind to the G beta gamma complex, but direct evidence for this is
      missing.

PMID- 7583641
TI  - Proteins with leucine-rich repeats.
AB  - Leucine-rich repeats are short sequence motifs present in over sixty proteins,
      all of which appear to be involved in protein-protein interactions. The crystal
      structure of ribonuclease inhibitor demonstrated that the repeats correspond to
      beta-alpha structural units. The recently determined crystal structure of the
      ribonuclease A-ribonuclease inhibitor complex suggests the basis for the protein
      binding function of leucine-rich repeats.

PMID- 7583639
TI  - The protein kinase C and protein kinase C related gene families.
AB  - Protein kinase C is an important target enzyme for lipid second messengers.
      Recent developments have focused on the tertiary structure analysis of domains
      present in protein kinase C and in combination with functional approaches such as
      mutagenesis and domain expression have generated a detailed understanding of the
      modular mechanism by which lipids cause activation. This provides a reference for
      the study of the protein kinase C-related kinases, a recently identified new
      class of kinases that are highly related to protein kinase C in their catalytic
      characteristics but have distinct regulatory features.

PMID- 7583642
TI  - Nucleic acids.

PMID- 7583643
TI  - Sequences and topology.

PMID- 7583644
TI  - Medical informatics: a real discipline?

PMID- 7583645
TI  - Medical informatics on the Internet: creating the sci.med. informatics newsgroup.
AB  - A Usenet newsgroup, sci.med.informatics, has been created to serve as an
      international electronic forum for discussion of issues related to medical
      informatics. The creation process follows a set of administrative rules set out
      by the Usenet administration on the Internet and consists of five steps: 1)
      informal discussion, 2) request for formal discussion, 3) formal discussion, 4)
      voting, and 5) posting of results. The newsgroup can be accessed using any news
      reader via the Internet.

PMID- 7583647
TI  - Trade-offs in producing patient-specific recommendations from a computer-based
      clinical guideline: a case study.
AB  - This case study explored 1) how much online clinical data is required to obtain
      patient-specific recommendations from a computer-based clinical practice
      guideline, 2) whether the availability of increasing amounts of online clinical
      data might allow a higher specificity of those recommendations, and 3) whether
      that increased specificity is necessarily desirable. The "quick reference guide"
      version of the guideline for acute postoperative pain management in adults,
      developed by the Agency for Health Care Policy and Research, was analyzed.
      Patient-specific data items that might be used to tailor the computer's output
      for a particular case were grouped into rough categories depending on how likely
      they were to be available online and how readily they might be determined from
      online clinical data. The patient-specific recommendations were analyzed to
      determine to what degree the amount of text produced depended on the online
      availability of different categories of data. An examination of example
      recommendations, however, illustrated that high specificity may not always be
      desirable. The study provides a concrete illustration of how the richness of
      online clinical data can affect patient-specific recommendations, and describes a
      number of related design trade-offs in converting a clinical guideline into an
      interactive, computer-based form.

PMID- 7583646
TI  - Discrete-event simulation of a wide-area health care network.
AB  - OBJECTIVE: Predict the behavior and estimate the telecommunication cost of a wide
      area message store-and-forward network for health care providers that uses the
      telephone system. DESIGN: A tool with which to perform large-scale discrete-event
      simulations was developed. Network models for star and mesh topologies were
      constructed to analyze the differences in performances and telecommunication
      costs. The distribution of nodes in the network models approximates the
      distribution of physicians, hospitals, medical labs, and insurers in the Province
      of Saskatchewan, Canada. Modeling parameters were based on measurements taken
      from a prototype telephone network and a survey conducted at two medical clinics.
      Simulation studies were conducted for both topologies. RESULTS: For either
      topology, the telecommunication cost of a network in Saskatchewan is projected to
      be less than $100 (Canadian) per month per node. The estimated telecommunication
      cost of the star topology is approximately half that of the mesh. Simulations
      predict that a mean end-to-end message delivery time of two hours or less is
      achievable at this cost. A doubling of the data volume results in an increase of
      less than 50% in the mean end-to-end message transfer time. CONCLUSION: The
      simulation models provided an estimate of network performance and
      telecommunication cost in a specific Canadian province. At the expected operating
      point, network performance appeared to be relatively insensitive to increases in
      data volume. Similar results might be anticipated in other rural states and
      provinces in North America where a telephone-based network is desired.

PMID- 7583648
TI  - Outcomes monitoring: adjusting for risk factors, severity of illness, and
      complexity of care.
AB  - Adjusting for risk factors, severity of illness, and complexity of care is
      important when comparing and interpreting outcomes. Current and future approaches
      for examining risk factors, severity of illness, and complexity of care are
      described within the contexts of administrative, economic, and clinical outcomes.
      Reasons why the current standardized instruments, computerized severity systems,
      and workload/intensity measurements, when used alone, are inadequate for outcomes
      monitoring are proposed. A more comprehensive model for outcomes monitoring is
      required, one that adjusts outcomes for risk factors, severity of illness, and
      complexity of care.

PMID- 7583649
TI  - Patient satisfaction and normative decision theory.
AB  - This article explores the application of normative decision theory (NDT) to the
      challenge of facilitating and measuring patient satisfaction. Patient
      satisfaction is the appraisal, by an individual, of the extent to which the care
      provided has met that individual's expectations and preferences. Classic decision
      analysis provides a graphic and computational strategy to link patient
      preferences for outcomes to the treatment choices likely to produce the outcomes.
      Multiple criteria models enable the complex judgment task of measuring patient
      satisfaction to be decomposed into elemental factors that reflect patient
      preferences, thus facilitating evaluation of care in terms of factors relevant to
      the individual patient. Through the application of NDT models, it is possible to
      use patient preferences as a guide to the treatment planning and care monitoring
      process and to construct measures of patient satisfaction that are meaningful to
      the individual. Nursing informatics, with its foundations in both information
      management and decision sciences, provides the tools and data necessary to
      promote care provided in accord with patient preferences and to ensure appraisal
      of satisfaction that aptly captures the complex, multidimensional nature of
      patient preferences.

PMID- 7583650
TI  - Care planning as a strategy to manage variation in practice: from care plan to
      integrated person-based record.
AB  - This article begins with a summary of the trend toward a person-based health
      record, and the need to integrate data from a variety of sources to achieve this.
      A project is described that demonstrated problems with the structure of nursing
      care plans. These problems affected the ability to integrate care plan data into
      a clinical database capable of analysis to link control of process with clinical
      outcome. A second project is described that focused on the development of data
      sets holding higher-level descriptions suitable for the maintenance of a person
      based record, but at a summarized level and with no clinical detail. Finally, a
      prototype care planning system is described that, while maintaining the data
      required by the Nursing Process, was more flexibly structured to support analysis
      and hierarchical levels of description.

PMID- 7583651
TI  - Informatics: the infrastructure for quality assessment and quality improvement.

PMID- 7583652
TI  - The importance of Internet Newsgroups.

PMID- 7583653
TI  - Structure-based design of a lysozyme with altered catalytic activity.
AB  - Here we show that the substitution Thr 26-->His in the active site of T4 lysozyme
      causes the product to change from the alpha- to the beta-anomer. This implies an
      alteration in the catalytic mechanism of the enzyme. From the change in product,
      together with inspection of relevant crystal structures, it is inferred that wild
      type T4 lysozyme is an anomer-inverting enzyme with a single displacement
      mechanism in which water attacks from the alpha-side of the substrate. In
      contrast, the mutant T26H is an anomer-retaining enzyme with an apparently double
      displacement mechanism in which a water molecule attacks from the opposite side
      of the substrate. The results also show that the mechanism of wild-type T4
      lysozyme differs from that of hen egg-white lysozyme even though both enzymes are
      presumed to have evolved from a common precursor.

PMID- 7583654
TI  - Structure of a single-cytidine hairpin loop formed by the DNA triplet GCA.
AB  - In certain contexts the DNA triplet GGA, when juxtaposed on opposite strands of a
      DNA duplex, shows the unusual property of pairing with itself in an antiparallel
      orientation to form the (GGA)2 motif. In this motif the central guanines do not
      pair but intercalate and stack between sheared G.A pairs. Similar studies with
      GCA triplets reveal that they do not form analogous paired (GCA)2 motifs but
      instead strongly promote formation of a hairpin, the structure of which is now
      reported here. The GCA hairpin loop consists of a single cytidine residue closed
      by a sheared G.A pair and this structure is discussed in the context of triplet
      expansions in triplet-repeat diseases.

PMID- 7583655
TI  - A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria
      has a novel D2-symmetric active site.
AB  - Bacteria expressing R67-plasmid encoded dihydrofolate reductase (R67 DHFR)
      exhibit high-level resistance to the antibiotic trimethoprim. Native R67 DHFR is
      a 34,000 M(r) homotetramer which exists in equilibrium with an inactive dimeric
      form. The structure of native R67 DHFR has now been solved at 1.7 A resolution
      and is unrelated to that of chromosomal DHFR. Homotetrameric R67 DHFR has an
      unusual pore, 25 A in length, passing through the middle of the molecule. Two
      folate molecules bind asymmetrically within the pore indicating that the enzyme's
      active site consists of symmetry related binding surfaces from all four identical
      units.

PMID- 7583656
TI  - Assembly of VP26 in herpes simplex virus-1 inferred from structures of wild-type
      and recombinant capsids.
AB  - The 1250 A diameter herpes simplex virus-1 (HSV-1) capsid shell consists of four
      major structural proteins, of which VP26 (approximately 12,000 M(r)) is the
      smallest. Using 400 kV electron cryomicroscopy and computer reconstruction, we
      have determined the three-dimensional structures of the wild-type capsid and a
      recombinant baculovirus-generated HSV-1 capsid which lacks VP26. Their difference
      map demonstrates the presence of VP26 hexamers attached to all the hexons in the
      wild-type capsid, and reveals that the VP26 molecule consists of a large and a
      small domain. Although both hexons and pentons are predominantly composed of VP5,
      VP26 is not present on the penton. Based on the interactions involving VP26 and
      the hexon subunits, we propose a mechanism for VP26 assembly which would account
      for its distribution. Possible roles of VP26 in capsid stability and DNA
      packaging are discussed.

PMID- 7583657
TI  - Meetings and membrane proteins.

PMID- 7583661
TI  - Untangling the pathophysiochemistry of beta-amyloid.

PMID- 7583660
TI  - Turning lysozyme upside down.

PMID- 7583658
TI  - A barrel in the stalk.

PMID- 7583659
TI  - Twixt form and function.

PMID- 7583663
TI  - Picture story. Considering a reducing plan.

PMID- 7583662
TI  - A taste of copper.
AB  - New structures of copper containing proteins with cupredoxin-like folds confirm
      earlier predictions, and reveal electron-transfer routes in cytochrome oxidase,
      while a new fold for amine-oxidase reveals a new use for copper in forming self
      derived quino-cofactor.

PMID- 7583664
TI  - Crystal structure of the haemopexin-like C-terminal domain of gelatinase A.
AB  - The crystal structure of the haemopexin-like C-terminal domain of gelatinase A
      reveals that it is a four-bladed beta-propeller protein. The four blades are
      arranged around a channel-like opening in which Ca2+ and a Na-Cl+ ion pair are
      bound.

PMID- 7583665
TI  - X-ray analysis reveals conformational adaptation of the linker in functional
      calmodulin mutants.

PMID- 7583667
TI  - NMR structure of an inhibitory R2 C-terminal peptide bound to mouse
      ribonucleotide reductase R1 subunit.
AB  - The structure of peptide N-AcYTLDADF when bound to the large subunit of mouse
      ribonucleotide reductase has been elucidated by transfer NOE. This structure
      suggests a general design for type 1 RR inhibitors.

PMID- 7583669
TI  - Structural features of the epsilon subunit of the Escherichia coli ATP synthase
      determined by NMR spectroscopy.
AB  - The tertiary fold of the epsilon subunit of the Escherichia coli F1F0 ATPsynthase
      (ECF1F0) has been determined by two- and three-dimensional heteronuclear (13C,
      15N) NMR spectroscopy. The epsilon subunit exhibits a distinct two domain
      structure, with the N-terminal 84 residues of the protein forming a 10-stranded
      beta-structure, and with the C-terminal 48 amino acids arranged as two alpha
      helices running antiparallel to one another (two helix hairpin). The beta-domain
      folds as a beta-sandwich with a hydrophobic interior between the two layers of
      the sandwich. The C-terminal two-helix hairpin folds back to the N-terminal
      domain and interacts with one side of the beta-domain. The arrangement of the
      epsilon subunit in the intact F1F0 ATP synthase involves interaction of the two
      helix hairpin with the F1 part, and binding of the open side of the beta-sandwich
      to the c subunits of the membrane-embedded F0 part.

PMID- 7583668
TI  - Mechanisms of growth for protein and virus crystals.
AB  - The growth of six protein and virus crystals was investigated in situ using
      atomic force microscopy. Most of the crystals grew principally on steps generated
      by two-dimensional nucleation on surfaces though some grew by development of
      spiral dislocations. Apoferritin grew by a rarely encountered mechanism, normal
      growth, usually associated only with melt or vapour phase crystallization. Cubic
      crystals of satellite tobacco mosaic virus (STMV) grew, at moderate to high
      levels of supersaturation, by the direct addition of three-dimensional nuclei
      followed by their rapid normal growth and lateral expansion, a mechanism not
      previously described to promote controlled and reproducible crystal growth from
      solutions. Biological macromolecules apparently utilize a more diverse range of
      growth mechanisms in their crystallization than any previously studied materials.

PMID- 7583666
TI  - High-resolution structural studies of the factor XIIIa crosslinking site and the
      first type 1 module of fibronectin.
AB  - The N-terminal domain of fibronectin undergoes factor XIIIa-catalysed
      crosslinking to fibrin, bacteria and collagen. The reactive glutamine residue is
      in an extended, random coil 'tail' of about 18 residues that would be accessible
      for crosslinking.

PMID- 7583670
TI  - Ca(2+)-bridging mechanism and phospholipid head group recognition in the membrane
      binding protein annexin V.
AB  - Structural evidence is presented for a 'Ca(2+)-bridging' mechanism, proposed for
      Ca(2+)-binding interfacial membrane proteins such as annexins, protein kinase C,
      and certain coagulation proteins. Crystal structures of Ca(2+)-annexin V
      complexes with phospholipid polar heads provide molecular details of 'Ca(2+)
      bridges' as key features in the membrane attachment exhibited by these proteins.
      Distinct binding sites for phospholipid head groups are observed, including a
      novel, double-Ca2+ recognition site for phosphoserine that may serve as a
      phosphatidylserine receptor site in vivo.

PMID- 7583671
TI  - Pseudospecific docking surfaces on electron transfer proteins as illustrated by
      pseudoazurin, cytochrome c550 and cytochrome cd1 nitrite reductase.
AB  - The structure of pseudoazurin from Thiosphaera pantotropha has been determined
      and compared to structures of both soluble and membrane-bound periplasmic redox
      proteins. The results show a matching set of unipolar, but promiscuous, docking
      motifs based on a positive hydrophobic surface patch on the electron shuttle
      proteins pseudoazurin and cytochrome c550 and a negative hydrophobic patch on the
      surface of their known redox partners. The observed electrostatic handedness is
      argued to be associated with the charge-asymmetry of the membrane-bound
      components of the redox chain due to von Heijne's 'positives-inside' principle.
      We propose a 'positives-in-between' rule for electron shuttle proteins, and
      expect a negative hydrophobic patch to be present on both the highest and lowest
      redox potential species in a series of electron carriers.

PMID- 7583675
TI  - Genetically engineered animal models of human neurodegenerative diseases.
AB  - The influence of a single gene, engineered to be normally or abnormally
      expressed, can be evaluated in vivo through the development of transgenic
      animals. Application of this approach in the study of human neurological problems
      is contributing to an increased understanding of the pathogenic components
      operative in a variety of disorders. These include Alzheimer's disease, prion
      encephalopathies, motor neuron disease such as amyotrophic lateral sclerosis, and
      fragile X syndrome, as well as a number of viral-mediated neurological disorders.
      These transgenic animals can also serve as models to investigate the possible
      involvement of additional genetic and environmental factors on the disease state.
      Moreover, transgenic animals can be used in the development of intervention
      strategies. The application of this powerful and increasingly popular tool to
      investigate neurodegenerative disorders is reviewed.

PMID- 7583672
TI  - Solution structure of a mammalian PCB-binding protein in complex with a PCB.
AB  - Metabolites of polychlorinated biphenyls (PCBs) bind with high affinity to
      uteroglobin, a small homodimeric protein that also binds progesterone. We present
      the solution structure of the reduced form of rat uteroglobin in complex with a
      PCB methylsulphone, (MeSO2)2-TCB. The structure reveals the molecular basis for
      the accumulation of (MeSO2)2-TCB by uteroglobin. The structure also shows how
      ligand binding and release might be controlled by reduction/oxidation of two
      intermolecular disulphide bonds. Breakage of these bonds induces a local
      unfolding of the N- and C-termini and a separation of helices creating a channel
      into the binding site. These effects make the ligand binding cavity readily
      accessible to entry of the ligand.

PMID- 7583676
TI  - 6-Hydroxydopamine lesion of the rat substantia nigra: time course and morphology
      of cell death.
AB  - The 6-hydroxydopamine (6-OHDA) model of nigral injury in rats has been in use as
      a standard animal model of parkinsonism for many years. While earlier studies
      established the time course for loss of catecholamine histofluorescence or
      tyrosine hydroxylase immunostaining in the cell bodies and terminals, these
      alterations in phenotypic expression do not define the time course of morphologic
      degeneration. We have therefore used a silver impregnation method to characterize
      the time course and morphology of the degeneration of neurons in the
      nigrostriatal system. Abundant neuronal death was observed in substantia nigra
      pars compacta (SNpc) as early as 12 hours after nigral 6-OHDA injection, and
      prior to any evidence of striatal terminal degeneration. From 1 to 7 days neuron
      death was accompanied by striatal fibre degeneration. After 7 days, fibre
      degeneration was no longer seen, but identifiable neuron death continued at low
      levels for as long as 31 days, and stained amorphous material was present at 60
      days. The morphologic pattern of cell death in the early phase was similar to
      that in the late phase, and included cytoplasmic silver deposits and dark
      staining of the nucleolus. At no time was the morphology of apoptosis observed.
      We conclude that neuron death is a progressive process following 6-OHDA lesion,
      with similar morphology throughout the course of degeneration.

PMID- 7583673
TI  - Structural model for the beta-amyloid fibril based on interstrand alignment of an
      antiparallel-sheet comprising a C-terminal peptide.
AB  - Amyloids are a class of noncrystalline, yet ordered, protein aggregates. A new
      approach was used to provide the initial structural data on an amyloid fibril-
      comprising a peptide (beta 34-42) from the C-terminus of the beta-amyloid protein
      -based on measurement of intramolecular 13C-13C distances and 13C chemical shifts
      by solid-state 13C NMR and individual amide absorption frequencies by isotope
      edited infrared spectroscopy. Intermolecular orientation and alignment within the
      amyloid sheet was determined by fitting models to observed intermolecular 13C-13C
      couplings. Although the structural model we present is defined to relatively low
      resolution, it nevertheless shows a pleated antiparallel beta-sheet characterized
      by a specific intermolecular alignment.

PMID- 7583677
TI  - Activation of the subthalamic nucleus and pedunculopontine tegmentum: does it
      affect dopamine levels in the substantia nigra, nucleus accumbens and striatum?
AB  - Parkinson's disease is a neurodegenerative disorder, of which the most prominent
      morphological feature is the progressive loss of dopaminergic nigrostriatal
      neurons. Increased glutamatergic transmission in the basal ganglia has been
      implicated in the pathophysiology of Parkinson's disease (PD). This study
      investigated whether death of substantia nigra (SN) dopaminergic neurons could be
      caused by the hyperactivity of afferent pathways resulting in the release of a
      toxic dose of excitatory amino acids in the SN. Twice-daily unilateral
      stimulation of the subthalamic nucleus (STN) for 21 days, using two different
      pulse frequencies and current strengths, significantly increased amphetamine
      induced rotation, whereas sham stimulated rats showed significantly reduced
      rotation. Striatal and SN dopamine (DA) levels were unaffected when compared to
      naive and sham stimulated rats. However, levels of the DA metabolite,
      homovanillic acid (HVA), were significantly higher in the ipsilateral anterior
      striata of rats that had been stimulated at high frequency (100 Hz) and low
      current (100 microA) as compared to sham treated animals. Stimulation of the
      pedunculopontine tegmentum (PPT), using a single kainic acid injection, did not
      affect DA concentration in the ipsilateral striatum and nucleus accumbens when
      compared to sham-treated rats. DA levels in the contralateral striatum and
      nucleus accumbens of lesioned rats were significantly higher than ipsilateral
      levels. DOPAC/DA ratios were lower in the contralateral striatum and nucleus
      accumbens, suggesting decreased DA turnover. Glutamic acid decarboxylase activity
      was significantly higher in the ipsilateral than the contralateral SN. The
      physical manifestations of PD require a large reduction in caudate and putamen DA
      levels and no such depletion was measured in this study.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7583674
TI  - A short linear peptide derived from the N-terminal sequence of ubiquitin folds
      into a water-stable non-native beta-hairpin.
AB  - A 16-residue peptide derived from the N-terminal sequence of ubiquitin forms a
      stable monomeric beta-hairpin that is estimated to be approximately 80% populated
      in aqueous solution. The peptide sequence has been modified from native ubiquitin
      by replacing the five residues found in a type I G1 bulged turn (Thr-Leu-Thr-Gly
      Lys) with four residues (Asn-Pro-Asp-Gly) to maximize the probability of forming
      a beta-turn. Unexpectedly, the bulged turn conformation is re-established in the
      beta-hairpin in solution with two consequences: a one-amino acid frameshift in
      the alignment of the peptide main chain occurs relative to the native hairpin,
      and side chains formerly on opposite faces of the hairpin are brought together on
      the same face. The presence of the bulged turn in native ubiquitin may help in
      the avoidance of the stable non-native register of amino acids found here which
      would be unproductive for folding.

PMID- 7583679
TI  - Peroxidation of synaptosomes alters the dopamine uptake complex but spares the
      exocytotic release of dopamine.
AB  - Synaptosomes, prepared from the striata of mice, and incubated for 1 h in a Krebs
      Ringer medium with the peroxidative combination of ascorbic acid (0.1 mM)/Fe2+ (1
      microM), lose their ability to take up [3H] dopamine. This effect is associated
      with a decrease in binding of the dopamine uptake inhibitor [3H] GBR 12783. The
      free radical scavenger trolox C (0.1 mM) and the Ginkgo biloba extract EGb 761
      (10 micrograms/ml) prevent both effects. Although submitted to these peroxidative
      conditions after loading with [3H] DA, superfused synaptosomes retain their
      ability to release [3H] DA when depolarized by high potassium concentrations (40
      mM). This release is higher than that observed when synaptosomes are incubated
      without ascorbic acid/Fe2+, and does not seem to depend upon peroxidation, since
      it is also observed when incubation is performed in the presence of the free
      radical scavengers EGb 761 (10 micrograms/ml) and trolox C (0.1 mM).

PMID- 7583678
TI  - Lipid peroxidation in brain: interactions of L-DOPA/dopamine with ascorbate and
      iron.
AB  - Recent reports have stressed an accumulation of iron and enhanced levels of lipid
      peroxides in the substantia nigra as essential factors in the pathogenesis of
      Parkinson's disease. Many investigators believe that tissue antioxidants, such as
      ascorbate, play a protective role. On the other hand, L-DOPA, which is used
      extensively to treat Parkinson's disease, undergoes autoxidation (as does
      dopamine), thus generating reactive oxygen species. We studied lipid peroxidation
      (LPO) in mouse brain homogenates and evaluated the effects of iron (5 microM
      ferric-ADP), L-DOPA, dopamine and ascorbic acid, added either alone or in
      mixtures. Ascorbic acid was used at levels of 0.5 mM or 2.0 mM, approximating
      those present normally in brain. LPO in brain homogenates was stimulated by the
      addition of either ascorbic acid or iron, as well as by a combination of the two,
      in agreement with other reports. The effects of L-DOPA were complex: L-DOPA
      strongly suppressed LPO both with and without added iron-ADP. In sharp contrast,
      however, when ascorbic acid was also added, L-DOPA no longer suppressed LPO;
      indeed, L-DOPA stimulated LPO in the presence of added iron and ascorbic acid.
      Dopamine behaved similarly to L-DOPA. When ascorbic acid was studied over a
      concentration range, LPO was stimulated at 0.5, 1, 2 or 3 mM, with or without
      added iron and/or dopamine; 5 and 10 mM ascorbic acid were either not as
      effective or suppressed LPO below control levels. Deferoxamine, a powerful iron
      chelator, greatly suppressed LPO under all conditions, as did
      diethylenetriaminepentaacetate (DTPA). Added superoxide dismutase had no
      effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583680
TI  - Intrastriatal dopamine infusion reverses compensatory increases in D2-dopamine
      receptors in the 6-OHDA lesioned rat.
AB  - Direct infusion of dopamine into the corpus striatum has been proposed as a
      potential approach for the treatment of Parkinson's disease. The present study
      examined the effect of intrastriatal dopamine infusion on D2-dopamine receptors
      in the 6-hydroxydopamine (6-OHDA) lesioned rat brain. The completeness of the 6
      OHDA-induced nigrostriatal injury was confirmed using [3H]-mazindol
      autoradiography and apomorphine-induced behaviour. Intrastriatal infusion of
      three different dopamine doses significantly reduced the apomorphine-induced
      behaviour. [3H]-spiperone autoradiography performed one day after the termination
      of dopamine infusion into the striatum revealed a dramatic reduction of D2
      dopamine receptor binding. The mean +/- SEM percent reduction of D2 receptor
      binding in the affected areas of the striatum was 28.8 +/- 1.0% for 4.74
      micrograms dopamine/h infusion rate, 35.0 +/- 1.6% for 9.48 micrograms dopamine/h
      infusion rate and 33.3 +/- 5.0% for 14.22 micrograms dopamine/h infusion rate
      when compared to the unlesioned side. Infusion of vehicle alone did not have any
      effect. The present results support the concept that intrastriatal dopamine
      infusion may be a useful therapeutic approach for the treatment of Parkinson's
      disease.

PMID- 7583684
TI  - Proliferating cell nuclear antigen immunohistochemistry in astrocytes in
      experimental Creutzfeldt-Jakob disease and in human kuru, Creutzfeldt-Jakob
      disease and Gerstmann-Straussler-Scheinker syndrome.
AB  - We have used immunohistochemical techniques and a monoclonal antibody against
      proliferating cell nuclear antigen (PCNA) to investigate the proliferative
      activity of glial cells in mice with experimental Creutzfeldt-Jakob disease
      (CJD), and in human cases of CJD, kuru and Gerstmann-Straussler-Scheinker
      syndrome (GSS). Only a small proportion of hypertrophic astrocytes showed PCNA
      immunoreactivity (labelling index, LI: 0-4.5%). PCNA-specific immunostaining was
      confined entirely to cell nuclei. During the early stages of illness, with
      minimal CJD pathology, PCNA-immunopositive nuclei were occasionally observed in
      the subependymal zone of experimentally infected mice. From 18 weeks
      postinoculation, PCNA-immunopositive astrocytes were most frequently found in the
      corpus callosum and cerebellar white matter; regions which characteristically
      exhibit robust vacuolation. No other cells, particularly no cells of microglial
      morphology, showed PCNA immunoreactivity. In human cases of kuru, CJD and GSS, no
      PCNA-immunopositive cells were detected despite the presence of numerous
      microglial cells and reactive hypertrophic astrocytes. These results indicate
      that only a limited proportion of astrocytes proliferate in the experimental
      models of subacute spongiform encephalopathies and that microglia are probably
      postmitotic cells.

PMID- 7583685
TI  - MRI assessment of the blood-brain barrier in a hamster model of scrapie.
AB  - Magnetic resonance (MR) imaging in combination with gadolinium
      diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement was used to investigate
      the integrity of the blood-brain barrier in a hamster model of scrapie (263K)
      during the clinical phase of the disease. The post Gd-DTPA images of the infected
      hamster brain showed marked enhancement, which was not present in control
      animals. These results suggest that blood-brain barrier function is disrupted in
      the clinically-affected animal.

PMID- 7583681
TI  - Synapse loss and gliosis in the molecular layer of the cerebral cortex in
      Alzheimer's disease and in frontal lobe degeneration.
AB  - Changes in density of synapses and astrocytes in the molecular layer of the
      frontal and parietal cortex were compared in Alzheimer's disease (AD) and frontal
      lobe degeneration of non-Alzheimer type (FLD). The investigation was limited to
      the molecular layer because it is possible in this part of the cortex to measure
      changes in synapses and astrocytes without contamination by nerve cell body
      changes. In the frontal pole synapse density declined by 40% in both FLD and AD
      whereas in the parietal area there was a 50% decrease in synapse density in AD
      but no significant change in FLD. Number of astrocytes showed an inverse
      relationship to synapse density. There was a significant increase in astrocytes
      in the frontal cortex in both FLD and AD but in the parietal cortex such an
      increase was seen only in AD. These results confirm previous reports of synapse
      loss in AD and demonstrate a similar loss in FLD in the frontal, but not parietal
      cortex. The findings underscore the regional pattern changes of FLD, previously
      shown for other parameters, and its difference from that of AD. We propose that
      these changes in molecular layer may be representative of the pathology (and the
      functional deficit) within the underlying cortical layers.

PMID- 7583682
TI  - Factors determining the morphology of beta-amyloid (A beta) deposits in Down's
      syndrome.
AB  - Immunostained preparations of the medial temporal lobe from patients with Down's
      syndrome (DS) were counterstained with cresyl violet to reveal the beta-amyloid
      (A beta) deposits and their associated cell populations. A beta deposits in the
      cornu Ammonis (CA) of the hippocampus were, on average, more strongly stained,
      less often directly associated with neurons and more often associated with glial
      cells than the adjacent areas of cortex. Cored deposits were more frequently
      recorded in sulci rather than gyri and were associated with more glial cells than
      the uncored deposits. Multiple regression analyses suggested there was a positive
      correlation in the cortex between A beta deposit size and the frequency of
      closely associated neurons, the correlation being most significant with larger (>
      25 microns) neurons. The morphology of A beta deposit was also correlated with
      the location of deposits in the cortex, CA and dentate gyrus but this factor was
      of lesser importance. No significant variation in the morphology of the A beta
      deposits was associated with the presence of blood vessels within or adjacent to
      the deposit. The data suggest that neuronal cell bodies are important in the
      initial formation of A beta deposits and glial cells with the development of more
      mature amyloid deposits.

PMID- 7583686
TI  - CSF and plasma amino acid levels in motor neuron disease: elevation of CSF
      glutamate in a subset of patients.
AB  - Fasting plasma and/or CSF amino acid levels have been measured in a group of 37
      patients with motor neurone disease (MND) and in 35 neurological control patients
      undergoing lumbar puncture prior to myelography. There were no significant
      differences in the plasma levels of 22 amino acids between the two groups. In
      CSF, there was a significant elevation of the glutamate level in the MND patients
      (P = 0.008). However, the MND group were heterogeneous with regard to CSF
      glutamate: 19/31 (61%) had levels within the normal range; eight (26%) had levels
      more than twice the upper limit of normal (> or = 10 mumol/l) and five (16%) had
      levels more than seven times normal (> or = 30 mumol/l). In a subset of seven MND
      patients there was a significant inverse correlation (rs = -0.775, P < 0.03)
      between CSF glutamate levels in life and the density of pre-synaptic glutamate re
      uptake sites in the lumbar spinal cord measured in a post-mortem autoradiographic
      study. A possible interpretation of these findings is that an abnormality of
      glutamate transport may underlie the increase in CSF glutamate. The
      identification of a subgroup of MND patients with high CSF glutamate levels may
      be important in evaluating the clinical response to antiglutamate therapeutic
      agents.

PMID- 7583683
TI  - Cerebrospinal fluid 'neuronal thread protein' comes from serum by passage over
      the blood-brain barrier.
AB  - Cerebrospinal fluid (CSF) biochemical markers for Alzheimer's disease (AD) would
      be of great value, both to improve clinical diagnostic accuracy and to increase
      our knowledge of the pathogenesis of the disorder. An increase in the CSF-level
      of 'neuronal thread protein' (pancreatic thread protein (PTP) immunoreactive
      material in the brain) has been suggested to be just such a biochemical marker.
      We have studied CSF 'neuronal thread protein'-like immunoreactivity (NTPLI) using
      a microparticle enzyme immunoassay. CSF-NTPLI did not differ significantly
      between AD type I (pure AD) and controls, but was significantly higher in AD type
      II (senile dementia) and vascular dementia (VAD) as compared with controls. Signs
      of blood-brain barrier (BBB) damage (elevated CSF/S albumin ratio) were found in
      both AD type II and in VAD, but not in AD type I. In a multiple ANOVA, with age
      and CSF/S albumin ratio as covariates, no significant difference in CSF-NTPLI
      between diagnostic groups was noted though both CSF/S albumin ratio and age (P <
      0.0001 and P < 0.001 respectively) were found to influence the CSF-NTPLI level.
      Since BBB function was found to influence the CSF-NTPLI level, we examined
      whether NTPLI was present in serum. Indeed, serum NTPLI was about 40 times higher
      than CSF-NTPLI in neurological patients. Moreover, there was a statistically
      significant correlation between S-NTPLI and CSF-NTPLI. Taken together, present
      findings suggest that most of NTPLI in CSF comes from the serum, by passage over
      the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583687
TI  - Alzheimer's disease: maladaptive synaptoplasticity hypothesis.
AB  - A deposition of amyloid is considered by many to be the principal causative event
      in Alzheimer's disease, with abnormal neurites, neurofibrillary tangles, cell
      loss, and dementia all occurring secondarily to this. This present hypothesis
      differs by proposing a maladaptive synaptoplastic response, in conjunction with
      an involution of cortico-cortical projection neurons, as the principal causative
      events. The specificity of the maladaptive synaptoplastic response for a
      subpopulation of human nerve cells is related to the evolutionary advancement of
      the association cortex and the adaptation of functionally connected brain
      regions.

PMID- 7583689
TI  - Dystrophic neurites define diffuse as well as core-containing senile plaques in
      Alzheimer's disease.

PMID- 7583690
TI  - An algorithm for analysing probed partial digestion experiments.
AB  - A partial digestion of DNA (e.g. cosmid. Lambda, YAC, chromosome) is performed
      and the lengths of thoses fragments which hybridize to a labeled probe are
      measured using gel electrophoresis. We give an efficient algorithm that takes as
      input this experimental data and proposes one or more candidate solutions. Each
      solution designates the location of each restriction site and specifies the
      endpoints of each fragment. (Further experiments can then be designed to select
      the correct solution from this small set of candidates.) The algorithm works well
      even when the experiment gives inexact values for the lengths.

PMID- 7583688
TI  - Serial studies of free radical and antioxidant activity in motor neurone disease
      and the effect of selegiline.

PMID- 7583691
TI  - A new data model for biological classification.
AB  - In the domain of biological classification, classifications are performed
      hierarchically. There are no standard classifications which are unanimously
      accepted by the community of each domain; many different interacting views of
      classification exist about the same data, and the discovery of new data results
      in changes to the existing classification. Even a single individual may change
      his or her own classification of a particular group. Since multiple
      classification views interact, they are semantically related. It is difficult to
      model this kind of dynamically evolving and semantically interacting
      classification system using traditional data models, which lack the structural
      flexibility necessary to support dynamic views of hierarchic classifications, and
      cannot properly capture the history of these complex interactions. We have
      developed a new data model which is suitable for supporting semantically
      interacting dynamic views of hierarchic biological classifications. On the basis
      of our new data model we have developed a prototype database system called HICLAS
      (HIerarchical CLAssification System); its domain is plant taxonomy. HICLAS is
      available through the Internet and an X-window interface has been implemented to
      support queries to classification data.

PMID- 7583692
TI  - Comparative analysis by independent contrasts (CAIC): an Apple Macintosh
      application for analysing comparative data.
AB  - CAIC is an application for the Apple Macintosh which allows the valid analysis of
      comparative (multi-species) data sets that include continuous variables.
      Comparison among species is the most common technique for testing hypotheses of
      how organisms are adapted to their environments, but standard statistical tests
      like regression should not be used with species data. Such tests assume
      independence of data points, but related species often share traits by common
      descent rather than through independent adaptation. CAIC uses a phylogeny of the
      species in the data set to partition the variance among species into independent
      comparisons (technically, linear contrasts), each comparison being made at a
      different node in the phylogeny. There are two partitioning procedures--one used
      when all variables are continuous, the other when one variable is discrete. The
      resulting comparisons can be analysed validly in standard statistical packages to
      test hypotheses about correlated evolution among traits, to estimate parameters
      such as allometric exponents, and to compare rates of evolution. Previous
      versions of the package have already been used widely; this version is simpler to
      use and works on a wider range of machines. The package and manual are freely
      available by anonymous ftp or from the authors.

PMID- 7583694
TI  - Automat and BLAST: comparison of two protein sequence similarity search programs.
AB  - Since the early 1980s, protein/DNA sequence similarity search has become of major
      importance to biologists, and the need for fast and efficient tools grows with
      the size of databanks. Two programs use the strategy of finite state
      deterministic automatons to accomplish these searches. One of these two is BLAST,
      which is now widely used, and the other Automat, which has just been published.
      The differences and similarities in their basic principles, their use and their
      performances are analysed in this paper in order to allow optimal use of these
      important softwares.

PMID- 7583693
TI  - LGANN: a parallel system combining a local genetic algorithm and neural networks
      for the prediction of secondary structure of proteins.
AB  - In this work we describe a parallel system consisting of feed-forward neural
      networks supervised by a local genetic algorithm. The system is implemented in a
      transputer architecture and is used to predict the secondary structures of
      globular proteins. This method allows a wide search in the parameter space of the
      neural networks and the determination of their optimal topology for the
      predictive task. Different neural network topologies are selected by the genetic
      algorithm on the basis of minimal values of mean square errors on the testing
      set. When the alpha-helix, beta-strand and random coil motifs of secondary
      structures are discriminated, the maximal efficiency obtained is 0.62, with
      correlation coefficients of 0.35, 0.31 and 0.37 respectively. This level of
      accuracy is similar to that previously attained by means of neural networks
      without hidden layers and using single protein sequences as input. The results
      validate the neural network topologies used for the prediction of protein
      secondary structures and highlight the relevance of the input information in
      determining the limit of their performance.

PMID- 7583695
TI  - A rapid access motif database (RAMdb) with a search algorithm for the retrieval
      patterns in nucleic acids or protein databanks.
AB  - We present here a codification structure, entirely interfaced with the main
      packages for biomolecule database management, associated with a new search
      algorithm to retrieve quickly a sequence in a database. This system is derived
      from a method previously proposed for homology search in databanks with a
      preprocessed codification of an entire database in which all the overlapping
      subsequences of a specific length in a sequence were converted into a code and
      stored in a hash-coding file. This new algorithm is designed for an improved use
      of the codification. It is based on the recognition of the rarest strings which
      characterize the query sequence and the intersection of sorted lists read in the
      codification structure. The system is applicable to both nucleic acid and protein
      sequences and is used to find patterns in databanks or large sets of sequences. A
      few examples of applications are given. In addition, the comparison of our method
      with existing ones shows that this new approach speeds up the search for query
      patterns in large data sets.

PMID- 7583697
TI  - NUVIEW: software for display and interactive manipulation of nucleic acid models.
AB  - The NUVIEW software package allows skeletal models of any double helical nucleic
      acid molecule to be displayed on a graphics monitor and to apply various
      rotations, translations and scaling transformations interactively, through the
      keyboard. The skeletal model is generated by connecting any pair of
      representative points, one from each of the bases in the basepair. In addition to
      the above mentioned manipulations, the base residues can be identified by using a
      locator and the distance between any pair of residues can be obtained. A sequence
      based color coded display allows easy identification of sequence repeats, such as
      runs of Adenines. The real time interactive manipulation of such skeletal models
      for large DNA/RNA double helices, can be used to trace the path of the nucleic
      acid chain in three dimensions and hence get a better idea of its topology,
      location of linear or curved regions, distances between far off regions in the
      sequence etc. A physical picture of these features will assist in understanding
      the relationship between base sequence, structure and biological function in
      nucleic acids.

PMID- 7583696
TI  - NUPARM and NUCGEN: software for analysis and generation of sequence dependent
      nucleic acid structures.
AB  - Software packages NUPARM and NUCGEN, are described, which can be used to
      understand sequence directed structural variations in nucleic acids, by analysis
      and generation of non-uniform structures. A set of local inter basepair
      parameters (viz. tilt, roll, twist, shift, slide and rise) have been defined,
      which use geometry and coordinates of two successive basepairs only and can be
      used to generate polymeric structures with varying geometries for each of the 16
      possible dinucleotide steps. Intra basepair parameters, propeller, buckle,
      opening and the C6...C8 distance can also be varied, if required, while the sugar
      phosphate backbone atoms are fixed in some standard conformation in each of the
      nucleotides. NUPARM can be used to analyse both DNA and RNA structures, with
      single as well as double stranded helices. The NUCGEN software generates double
      helical models with the backbone fixed in B-form DNA, but with appropriate
      modifications in the input data, it can also generate A-form DNA and RNA duplex
      structures.

PMID- 7583699
TI  - An image-processing approach to dotplots: an X-Window-based program for
      interactive analysis of dotplots derived from sequence and structural data.
AB  - We present an approach to the study of the relationships between biological
      sequences and structures applying image analysis methods to dotplots. We
      introduce a set of analytical tools based on different types of digital image
      processing filters that are new within the context of dotplots. We have
      reformulated some of the usual approaches in dotplot analysis as mathematical
      operations on images within the framework of mathematical morphology. An X-Window
      based implementation of this new approach has been developed and is available by
      anonymous FTP.

PMID- 7583701
TI  - DNAView: a quality assessment tool for the visualization of large sequenced
      regions.
AB  - This communication describes DNAView, a graphical tool for the visualization and
      printing of large nucleic acid sequences. DNAView uses color coding to compactly
      display genomic segments of up to 100 kb on a single printed page. The specific
      color schemes integrated into DNAView can highlight 'local aggregate' properties
      of large segments of DNA. We have also incorporated a confidence expression for
      the assigned sequence. This is represented by base color intensity that is
      proportional to the number of times that base was sequenced. Areas of interest,
      such as exons, introns, repetitive elements and splice sites, can be emphasized
      using overlays. The colored image can be saved in a standard TIFF image file
      format that may be imported and annotated by other application software.

PMID- 7583698
TI  - Analysis of transcription control signals using artificial neural networks.
AB  - The role of the upstream region in controlling the transcription efficiency of a
      gene is well established. However, the question of predicting the extent of gene
      expressed given the upstream region has so far remained unresolved. Using an
      artificial neural network (ANN) to capture the internal representation associated
      with the transcription control signal, the present work predicts the rate of mRNA
      synthesis based on the pattern contained in the upstream region. Further, the
      model has been used to predict the transcription efficiency for all possible
      single base mutations associated with the beta-globin promoter. The simulation
      results reveal that apart from the experimental observation that alpha-79G-A and 
      78G-A mutation increases the efficiency of transcription, mutation in these
      regions by C or T also causes an increase in transcription. Furthermore the
      simulation results verify that mutations in the conserved region, in general,
      decrease the transcriptional efficiency. However, the results also show that
      certain sequence elements, when mutated, either cause a marginal increase in the
      level of transcription or have no effect on transcription levels. The simulation
      results can be used as a guide in designing mutation experiments since an a
      priori estimate of the possible outcome of a mutation can be obtained.

PMID- 7583700
TI  - A parallel neural network simulator on the connection machine CM-5.
AB  - We here present a parallel implementation of artificial neural networks on the
      connection machine CM-5 and compare it with other parallel implementations on
      SIMD and MIMD architectures. This parallel implementation was developed with the
      goal of efficiently training large neural networks with huge training pattern
      sets for applications in molecular biology, in particular the prediction of
      coding regions in DNA sequences. The implementation uses training pattern
      parallelism and makes use of the parallel I/O facilities of the CM-5 and its
      efficient reduction operations available within the control network to achieve a
      high scalability. The parallel simulator obtains a maximum speed of 149.25 MCUPS
      for training feedforward networks with backpropagation on a 512 processor CM-5
      system without using the CM-5 vector facility. The implementation poses no
      restriction on the type of network topology and works with different batch
      training algorithms like BP. Quickprop and Rprop.

PMID- 7583702
TI  - Co-inertia analysis of amino-acid physico-chemical properties and protein
      composition with the ADE package.
AB  - A multivariate analysis method called co-inertia analysis was used to determine
      the main relationships between two data tables having identical rows. This method
      is available in the ADE multivariate analysis package for Macintosh micro
      computers. It was applied to two data sets, one containing the amino-acid
      composition of 999 E. coli proteins, and the other the values of 402 physico
      chemical properties for the 20 natural amino-acids. There were strong
      relationships between amino-acid physico-chemical properties and the composition
      of proteins. The first common factor was hydrophobicity; it is linked to the
      biological environment of proteins, either in the cytoplasm (or outside the
      cell), or in the nonpolar environment of the phospholipid bilayer of biological
      membranes. The second factor linked the expressivity of protein genes and the
      propensity of amino-acids to form alpha helix/beta sheets. The third factor
      showed that heavy, aromatic amino-acids tend to be avoided, except when they are
      needed for structural or functional reasons. These results are discussed in terms
      of selective pressure acting on amino-acid composition of proteins.

PMID- 7583704
TI  - Treatment of neurotoxic side effects of interferon-alpha with naltrexone.
AB  - Interferon-alpha (IFN-alpha) has potential dose-limiting neurotoxic side effects
      when used in cancer therapy. The nature of this neurotoxicity is speculative, and
      there is no definitive treatment. Because animal studies suggest that IFN-alpha
      acts at opioid receptor sites, we gave naltrexone, a long-acting opioid
      antagonist, to 9 patients who had hematological malignancies and who suffered
      from IFN-alpha side effects. Seven of these patients experienced complete or
      moderate relief of side effects. Five of the patients tested before and during
      naltrexone treatment showed improvement of cognitive functioning. Two patients
      could not tolerate naltrexone side effects. This study suggests an intervention
      against IFN-alpha side effects and provides support for the role of opioid
      receptor interaction in IFN-alpha neurotoxicity.

PMID- 7583703
TI  - DNASUN: a package of computer programs for the biotechnology laboratory.
AB  - The paper describes a new software package DNASUN developed for supporting gene
      engineering laboratories. The package provides a user-friendly interface for
      experimental researches and supports the traditional nucleotide/protein sequence
      analysis as well as physical mapping, sequencing, plasmid manipulations, optimal
      oligonucleotide probe selection and other common molecular biology procedures.

PMID- 7583705
TI  - Chemotherapy rapidly alternating with twice-a-day accelerated radiation therapy
      in carcinomas involving the hypopharynx or esophagus: an update.
AB  - Laboratory studies have suggested that rapidly alternating chemotherapy and
      radiation therapy might act synergistically. We undertook this study to evaluate
      the toxicity and effectiveness of this approach in patients with carcinoma
      involving the hypopharynx or esophagus. Between 1987 and 1991, we treated 47
      patients (23 with carcinoma involving the hypopharynx and 24 with carcinoma
      involving the esophagus) by three cycles of chemotherapy (during weeks 1, 4, and
      7) rapidly alternating with twice-a-day radiation therapy (during weeks 2, 5, and
      8). Chemotherapy consisted of cisplatin 100 mg/m2 and 5-fluorouracil 3-4 g/m2
      given over 4 days. Radiation therapy consisted of 180-200 cGy twice each day to
      2000 cGy/cycle, total 6000 cGy over 7 weeks. The histology was squamous cell
      carcinoma in 44 patients and adenocarcinoma in 3 patients with esophagus cancer.
      Median follow-up is 2 years (range 1-5 years). The observed survival rate for all
      47 patients was 54% at 1 year and 38% at 2 years. Acute toxicity was
      considerable. Twelve patients (25%) died during therapy from toxicity, without
      tumor progression, leaving 35 patients (18 hypopharynx, 17 esophagus) evaluable
      for response. Among the hypopharyngeal patients, 83% had a complete response, 11%
      had a partial response, and 6% had no response. Among the esophageal patients,
      94% had a complete response, and 6% had a partial response. Local control was
      better for the esophageal patients than the hypopharyngeal patients (98% vs. 52%
      at 2 years, p = 0.038). The incidence of distant metastases was 25% at 2 years
      and not significantly different between the two groups. A high rate of local
      control was achieved, particularly in esophageal cancer, by delivering
      chemotherapy and radiation therapy in a rapidly alternating fashion. This was
      achieved at a considerable cost in terms of toxicity, however. Although our
      response rates and local control compare favorably with those of other recently
      published studies of combined modality therapy in esophagus or head and neck
      cancer, much additional work is required to reduce the toxicity and, in
      hypopharyngeal cancer, to further improve the local control.

PMID- 7583706
TI  - Diagnosis of breast carcinoma with radiolabeled monoclonal antibodies (MoAbs) to
      carcinoembryonic antigen (CEA) and human milk fat globulin (HMFG).
AB  - The current study attempted to assess the potential proficiency of
      radioimmunodetection (RAID) of primary, residual, multicentric, and recurrent
      breast carcinoma using two radiolabeled murine monoclonal antibodies (MoAbs),
      anti-human milk fat globulin (HMFG1) labeled with iodine (123I) and anti
      carcinoembryonic antigen (CEA) labeled with technetium (99Tc). Thirteen patients
      with suspicious clinical and/or mammographic primary or recurrent breast
      carcinoma were studied in a phase I-II prospective, consecutive, nonrandomized,
      noncontrolled study. Five patients received intravenous infusion with 0.5-2.0 mg
      anti-CEA MoAb type CYT 380 labeled with 99Tc [13-22 millicurie (mCI)] and 8
      patients received intravenous infusion with 0.25-1.0 mg anti-HMFG1 MoAb (Unipath,
      U.K.) labeled with 123I (4-17 mCI). Both MoAbs used in this study demonstrated
      ability to bind specifically to breast cancer lesions, resulting in successful
      RAID in 10 of 12 of studied patients (5 of 5 patients in the anti-CEA-99Tc and 5
      of 7 in the anti-HMFG-123I group--accuracy 83.3%). One patient was excluded due
      to protocol violation. Seven patients had true-positive scans when correlated
      with surgery (sensitivity 87.5%). The MoAb scans accurately diagnosed lesions in
      3 of the 4 primary invasive breast carcinomas confirmed histologically. Presence
      of residual carcinoma following wide excision was established in 1 of 2 patients
      and presence of soft tissue metastases in 3 patients. Three patients had true
      negative scan (specificity 75%): 2 patients presented with suspicious
      mammographic recurrence postlumpectomy and 1 patient had questionable soft tissue
      recurrence. One patient with primary breast carcinoma had a false-negative scan
      and another had a false-positive scan in the presence of fibrosis following
      lumpectomy and radiation therapy. No adverse reactions were noted in the patients
      studied. RAID findings were confirmed by immunohistochemistry in 6 of 9 cases
      studied. Our data suggest that radiolabeled MoAbs used in this study are
      potentially useful diagnostic agents for evaluation of primary or recurrent
      breast carcinoma, particularly in the areas where conventional methodology is
      limited.

PMID- 7583708
TI  - Suppression of tumor cell growth by anthocyanins in vitro.
AB  - Bioflavonoids, extracted from flower petals, were examined for their growth
      inhibitory effect on cells in culture. They were found to significantly suppress
      the growth of the cultured cells. Anthocyanins tended to show greater inhibitory
      effect than other flavonoids. Commercially synthesized or purified aglycones of
      flavonoids were also studied for their suppression of tumor cells. The
      anthocyanins were more effective than other flavonoid aglycones, although the
      aglycones were easily inactivated under the culture conditions.

PMID- 7583707
TI  - Increase of plasma transforming growth factor beta (TGF beta) during
      immunotherapy with IL-2.
AB  - Interleukin-2 (IL-2) is a lymphokine with pleiotropic activities on the immune
      system. When administered in vivo, besides inducing unrestricted tumor
      cytotoxicity, it is also responsible for the secondary release of other
      lymphokines, such as IL-1, TNF, and marrow growth factors, which may mediate some
      of the clinical toxicities (as well as therapeutic effects) seen during IL-2
      immunotherapy. Among the clinical effects of IL-2, we previously reported
      thrombocytopenia and IL-2-induced in vitro inhibition of platelet aggregation
      accompanied by rapid secretion of alpha-granule components such as platelet
      factor 4 (PF4) and beta-thromboglobulin. Platelets constitute one of the largest
      storage forms of TGF beta. Preliminary evaluation of this factor in patients
      receiving IL-2 had indicated that plasma TGF beta activity increased in cancer
      patients following IL-2 therapy. We report a more detailed study of the
      quantitation of TGF beta activity in the plasma of 23 cancer patients treated
      with IL-2 immunotherapy. Of interest, we found that although elevation of the
      bioactive form of TGF beta occurred in most patients during IL-2 therapy, it was
      significantly higher in patients with clinical regression of tumor (p = .004). In
      the first 2 weeks of therapy increase of plasma TGF beta activity appeared to
      correlate with a decrease of platelet counts, suggesting that the factor may
      derive from the storage form of TGF beta contained therein.

PMID- 7583710
TI  - Radiation recall dermatitis induced by edatrexate in a patient with breast
      cancer.
AB  - Enhancement of radiation injury to the skin and mucous membranes has been
      observed with a number of chemotherapeutic agents. A 32-year-old woman with
      metastatic breast cancer received local radiation therapy to the lumbosacral
      area. Six weeks later, systemic edatrexate therapy was initiated and a localized
      painful erythema with edema and a vesicular eruption occurred over the previous
      site of radiation therapy. Physicians should be aware that edatrexate can cause
      radiation recall, and that careful use of anti-inflammatory agents may allow
      continued chemotherapy treatment.

PMID- 7583709
TI  - Effect of human recombinant interferon-alpha on the activity of cis
      diamminedichloroplatinum(II) in human non-small cell lung cancer xenografts.
AB  - Interferons (IFNs) augment the effect of some antitumor agents, including cis
      diamminedichloroplatinum(II) (cDDP), in experimental systems. The effect of human
      recombinant interferon-alpha 2b (rIFN alpha) on the cDDP-dependent growth delay
      of a human non-small cell lung cancer established as a xenograft in nude mice
      (NX002) has been investigated. IFN (10(5) IU/mouse, s.c.) as a single agent had
      no effect on the growth of the xenograft. cDDP (4.2 mg/kg, i.p.) caused a
      specific growth delay of 0.42, and this delay was significantly enhanced (to
      1.08) by concomitant dosing with the otherwise inactive IFN. Possible mechanisms
      for this supra-additive relationship between IFN and cDDP have been investigated:
      increased intratumoral accumulation of platinum was seen at late time points
      (maximally at 36 hr) during the pharmacokinetic beta-phase of cDDP elimination
      from the plasma of the nude mice. Tumor:plasma platinum concentration ratios at
      36-48 hr indicated significantly increased accumulation of platinum in tumors
      from IFN-treated mice compared to controls (p < 0.05). Scheduling experiments
      suggest that this IFN-mediated effect can persist for 4 hr. These differences may
      account for the enhanced antitumor activity of cDDP when coadministered with IFN.

PMID- 7583714
TI  - Is there a role for intraperitoneal therapy in the management of gastrointestinal
      malignancies?

PMID- 7583712
TI  - Local surgical treatment of rectal cancer.
AB  - Patients with cancer of the lower third of the rectum can avoid both the
      morbidity of an APR and the need for a permanent colostomy by having the cancer
      removed by local excision. If the surgeon clinically suspects that a patient has
      an early cancer, the first step should be local excision of the tumor. The
      pathological features of the cancer specimen will then indicate the next step in
      treatment. This can range from no further therapy to proctectomy with or without
      an anastomosis (Table 2). Patients with a low risk of local failure can be
      treated by excision alone. Those with a higher risk of local failure should
      undergo APR or LAR or enter a protocol to determine the role of local excision
      and adjuvant chemoradiation.

PMID- 7583713
TI  - The cell cycle as therapeutic target.
AB  - Approved by the FDA in 1991 with indications for acceleration of neutrophil
      recovery in several clinical settings, CSFs may prove clinically useful in ways
      beyond hemorestoration. Myeloprotection conferred by GM-CSF may enable higher
      doses of chemotherapy to be given with only short intervals between cycles.
      Priming may make resting AML blasts more chemosensitive. Mobilization of
      peripheral blood stem cells may facilitate and even improve autologous stem cell
      transplantation.

PMID- 7583715
TI  - Some tumor cell protein kinases activated by receptors as markers, including
      elastin receptors.

PMID- 7583717
TI  - Genetics of chromosome 11: loci for pediatric and adult malignancies,
      developmental disorders, and other diseases.

PMID- 7583716
TI  - The metabolism service.
AB  - The Metabolism Branch, originally the Metabolism Service, created by Mider and
      Zubrod largely in the image that Mider had projected, has had two leaders: Berlin
      (1956-1971) and Waldmann (1971-present). The original design of a comparatively
      small senior staff of five Senior Investigators and 10 Clinical Associates
      (fellows), together with an 11-bed patient care unit in close proximity to the
      offices and laboratories, has in essence continued to the present with a
      comparatively small expansion under Waldmann. This unit has served as a training
      ground. Among its present members and alumni there are 18 members of the
      Association of American Physicians (AAP) and 22 members of the American Society
      of Clinical Investigation (ASCI). In 1994, two of the presidents of the clinical
      research societies, Rosenberg of the AAP and Berzofsky of the ASCI, are from the
      Service's ranks. This model, some would say paradigm, for the organization and
      function of clinical research units could be an answer to what Ahrens has called
      a crisis. The Metabolism Branch had the benefit of strong leadership from the
      NCI, particularly Endicott, The Director in the 1960s, and Mider and Zubrod, the
      Scientific Directors. There can be no doubt that the Branch benefited
      substantially, some would say enormously, from the doctor draft of the 1950s and
      1960s and from the funding of the intramural research program as an integral part
      of the funding of each of the National Institutes.

PMID- 7583711
TI  - Disabling encephalopathy during 5-fluorouracil and levamisole adjuvant therapy
      for resected colorectal cancer: a report of two cases.
AB  - We observed leukoencephalopathy in 1 patient, and progressive dementia in
      another, during the administration of 5-fluorouracil (5-FU) and levamisole. A
      retrospective search, among 80 other patients with resected colorectal cancer
      receiving 5-FU and levamisole as adjuvant therapy, 166 resected malignant
      melanoma patients receiving adjuvant levamisole, and 254 advanced colorectal
      cancer patients receiving 5-FU often combined with leucovorin, for other cases of
      encephalopathy was negative. The frequency of this neurotoxicity is low (about 2%
      of patients receiving 5-FU and levamisole), but it appears specific for this
      combination of drugs. The lack of complete reversibility on stopping the drugs is
      worrisome, as this therapy is used to improve the curability of resected colon
      cancer.

PMID- 7583719
TI  - The metabolism branch: an exemplar of patient-oriented research.

PMID- 7583718
TI  - Re: "Local surgical treatment of rectal cancer".

PMID- 7583720
TI  - Health care reform.

PMID- 7583721
TI  - Creighton University to open hereditary cancer prevention clinic.

PMID- 7583722
TI  - Ultrasonography of the fetal neck in the second and third trimesters. Part 3.
      Anomalies of the anterior and anterolateral nuchal region.
AB  - Current ultrasound instrumentation yields high-resolution scans that allow
      accurate assessment of the fetal neck. Most neck structures are normally small
      and barely visible, so anomalous development can be easily identified, for
      example, when the nuchal fold is measured in the second trimester. The author
      examined the anterior and anterolateral nuchal region in a total of 15,200 second
      and third-trimester scans obtained over a 10-year period. The abnormalities
      identified were differentiated with respect to their position (at the central
      midline or anterolateral or lateral to the midline) and ultrasonographic
      characteristics (solid, cystic or mixed; calcified or vascular). This pictorial
      essay depicts the ultrasonographic appearance of masses that can be detected
      antenatally, including thyroid masses, teratoma, thyroglossal duct cyst, cystic
      hygroma, hemangioma, branchial cleft cyst and other developmental cystic lesions.
      In addition, the methods of elucidating these lesions is described.

PMID- 7583723
TI  - Magnetic resonance imaging of lateral ventricular tumours.
AB  - The authors review their experience with magnetic resonance imaging (MRI) of
      giant lateral ventricular tumours, placing special emphasis on the imaging
      features that aid in the differential diagnosis. The tumours illustrated include
      astrocytoma, oligodendroglioma, neurocytoma, subependymoma, metastatic lesions
      and subependymal giant cell astrocytoma. Because of their large size, most of
      these lesions cause hydrocephalus. The presence of associated edema indicates
      direct brain invasion or a higher grade of tumour differentiation. The degree and
      pattern of contrast enhancement, as well as the signal characteristics before
      administration of contrast agent, are nonspecific. The location of the tumour
      within the lateral ventricles and the patient's age are the most helpful
      diagnostic clues. Giant lateral ventricular tumours are uncommon, and the
      patients usually come to clinical attention with symptoms related to increased
      intracranial pressure. MRI assists in surgical planning by defining the exact
      location of the lesion and its relation to adjacent structures. Although the
      signal characteristics and patterns of contrast enhancement are nonspecific,
      preoperative diagnosis is possible in most cases if the imaging findings are
      correlated with the patient's age and the specific location of the tumour within
      the lateral ventricles.

PMID- 7583724
TI  - Comparison of helical and conventional computed tomography of the liver.
AB  - OBJECTIVE: To compare helical and conventional computed tomography (CT) of the
      liver in terms of enhancement (with different contrast media) and image quality,
      using optimal technique for each type of acquisition. PATIENTS AND METHODS: Of
      218 consecutive patients referred to a tertiary-care hospital for CT of the
      liver, 166 were randomly assigned to undergo helical (79 patients) or
      conventional (87) CT. Fifty patients were excluded from the study because they
      were unable to hold their breath or were unable to cooperate or because they
      weighted more than 120 kg. Two other patients were excluded at the time of
      scanning because of a technical problem. Monophasic injections of contrast agent
      at 3 mL/second were given to patients undergoing helical CT and biphasic
      injections at 2 and 0.7 mL/second to patients undergoing conventional CT. The
      contrast media used were iothalamate meglumine, ioversol, iopamidol and iohexol.
      For each patient, liver enhancement over baseline attenuation was calculated for
      every slice, and time to peak enhancement was calculated. In addition,
      visualization of anatomic landmarks and image quality were scored by two
      independent reviewers. RESULTS: Minimum, maximum and mean liver enhancement were
      significantly greater in the group that underwent helical imaging (49, 62 and 55
      Hounsfield units [HU] respectively) than in the group that underwent conventional
      imaging (36, 51 and 44 HU respectively) (Student's t-test, p < 0.0001). Similar
      differences were obtained when the results were analysed separately for each
      contrast medium. Image quality was not significantly different between the two
      acquisition modes. CONCLUSIONS: For computed tomography of the liver, monophasic
      injection of contrast medium at a high rate and helical acquisition (rather than
      biphasic injection and conventional acquisition) resulted in significantly better
      enhancement, without compromising image quality.

PMID- 7583725
TI  - Dimenhydrinate pretreatment in patients receiving intra-arterial ioxaglate:
      effect on nausea and vomiting.
AB  - OBJECTIVE: To determine the effectiveness of the antihistamine dimenhydrinate
      (Dramamine) as a prophylactic agent against the nausea and vomiting that
      occasionally accompany the use of ioxaglate. PATIENTS AND METHODS: Three hundred
      patients (165 men and 135 women, ranging in age from 18 to 89 [mean 62] years)
      undergoing noncoronary arteriography received dimenhydrinate or placebo before
      the injection of the low-osmolality contrast material ioxaglate (Hexabrix). The
      patients were observed and questioned about nausea and vomiting, as well as many
      other possible reactions to the contrast material. RESULTS: There were no
      statistical differences in the occurrence of adverse reactions between the groups
      receiving dimenhydrinate and placebo (chi 2 or Fisher's exact test, p > 0.05).
      CONCLUSION: Dimenhydrinate, as administered in this study, was ineffective as a
      prophylactic agent against adverse reactions accompanying administration of
      ioxaglate.

PMID- 7583726
TI  - Giant cell tumour of the seventh cervical vertebra.
AB  - A 43-year-old man presented with bubbly expansion and rarefaction of the body of
      the seventh cervical vertebra. The lesion involved the right side of the
      vertebral arch and had a soft-tissue component extending mainly anterior to the
      vertebra. Histopathologic examination of the specimen obtained by open biopsy
      revealed a giant cell tumour. Giant cell tumours of the spine, excluding the
      sacrum, are rare. Radiographically, they may be confused with metastatic
      carcinoma, plasmacytoma, lymphoma, chordoma and even benign lesions, particularly
      aneurysmal bone cyst and brown tumour of hyperparathyroidism. However, giant cell
      tumour occurs mainly in younger patients, involves the vertebral body selectively
      in most cases and has a bubbly appearance associated with rarefaction and
      expansion of the vertebral body, characteristics that may be helpful in the
      diagnosis.

PMID- 7583727
TI  - Facial artery pseudoaneurysm: diagnosis by colour Doppler ultrasonography.
AB  - Pseudoaneurysms of the facial region are rare and usually result from direct
      penetrating or blunt trauma. The authors report a pseudoaneurysm of the facial
      artery in a 22-year-old man injured in a motor vehicle accident. Colour Doppler
      ultrasonography was used to locate the aneurysm sac and establish its relation to
      the adjacent facial artery. Successful operative repair of the aneurysm was
      performed on the basis of the sonographic findings alone, without selective
      angiography.

PMID- 7583729
TI  - Antegrade placement of a ureteric stent by a pull-through technique.
AB  - Internal double-J ureteric stents are valuable in the treatment of ureteric
      obstruction, obviating the need for an external drainage catheter. Retrograde
      placement of these stents is often performed by the urologist, or, if such
      placement fails, antegrade placement is performed by the interventional radiology
      service. In cases of high-grade obstruction it may be possible to pass a guide
      wire through the stricture but impossible to do so with a catheter. The authors
      describe a pull-through technique, which was used to place a ureteric stent in a
      65-year-old man with bilateral hydronephrosis. The method consists of gaining
      control of the distal end of the guide wire by retrieving it through the penile
      urethra to allow the stenosis to be crossed with a catheter.

PMID- 7583728
TI  - Multiple cardiac masses diagnosed with prenatal ultrasonography in the fetus of a
      woman with tuberous sclerosis.
AB  - Cardiac rhabdomyomas are associated with tuberous sclerosis, but their
      identification in utero is uncommon. The authors report a case of multiple
      cardiac masses discovered in utero by prenatal ultrasonography at about 30 weeks
      gestational age. Follow-up included neonatal echocardiography, ultrasonography
      and computed tomography of the head. The differential diagnosis of echogenic
      intracardiac masses, as well as their management, is discussed.

PMID- 7583730
TI  - Fatigue fracture of the sacrum in a child.
AB  - The authors describe a 9-year-old girl with stress fracture of the sacrum. Such
      fractures can cause low-back or hip pain in children but may not be evident on
      plain films. The appearance on scintigraphy is not diagnostic. Likewise, the
      findings on magnetic resonance imaging may be nonspecific or confusing, because
      changes in signal intensity in the marrow may not be sufficient to distinguish
      infection or malignancy from healing of the fracture. Computed tomography can be
      more specific in delineating a sclerotic fracture oriented parallel to the
      sacroiliac joint. Recognition of the characteristic radiographic findings in
      sacral fatigue fractures can prevent incorrect diagnosis and unnecessary
      diagnostic procedures or treatments.

PMID- 7583731
TI  - A technique for preoperative localization of osteoid osteoma.
AB  - Preoperative localization of osteoid osteoma using a bone biopsy needle and
      methylene blue tissue staining is quick, inexpensive, accurate and easy to
      perform. This technique allows the surgeon to limit resection to the nidus of the
      lesion and minimal surrounding bone. No hardware is left in situ, so the surgical
      exposure and dissection planes are not limited by localization hardware.

PMID- 7583733
TI  - Menkes disease and occipital horn syndrome.

PMID- 7583732
TI  - Residents' corner. Answer to case of the month #34. Partial jejunal obstruction
      caused by a large phytobezoar.

PMID- 7583734
TI  - Sexual dysfunctions: relationship to childhood sexual abuse and early family
      experiences in a nonclinical sample.
AB  - Studies investigating a possible relationship between childhood sexual abuse and
      adult sexual dysfunction have reported highly discrepant results. The purpose of
      the present study was to examine 202 female university students for early
      familial experience and childhood sexual abuse in relation to adult sexual
      disorders. Each student was asked to complete three questionnaires on
      victimization, sexual dysfunction, early familial experiences. Results indicated
      that: (a) victims of multiple CSA more frequently reported sexual desire
      disorders and orgasm disorders than did single-incident victims and nonvictims;
      (b) single-incident victims and nonvictims reported no significantly different
      rates for any kind of sexual dysfunction; (c) negative early familial experiences
      were significantly related to any kind of sexual disorder; and (d) women who
      reported orgasm disorders more often reported an inadequate sex education than
      did women with another or no sexual dysfunction. The data suggest that both
      family dysfunction and sexual victimization contribute to sexual disorders in
      adulthood, and that later sexual disorders are to a large extent the result of
      sexual abuse-related factors in particular and family dysfunction in general.

PMID- 7583735
TI  - Child sexual abuse: psychosocial aspects of 101 cases seen in an urban Malaysian
      setting.
AB  - This paper describes a case note and interview study of a cross sectional sample
      comprised of all children seen and confirmed as being sexually abused between
      June 1985 and December 1990 by the Suspected Child Abuse and Neglect (SCAN) Team
      of Kuala Lumpur General Hospital. A total of 101 cases, which represented 18.2%
      of all child abuse cases, were seen together with their accompanying adults.
      Information about ethnicity, socioeconomic status, family constellation
      relationship of perpetrator to the child, and reported psychosocial factors that
      could have contributed towards the abuse were recorded. The Indian ethnicity
      group was found to be overrepresented. The mean age of children was 6-8 years, SD
      4.1, with age ranging 1.5-16 years. Forty-one and one-half percent were in the
      age range 5-9 years. Among the important associated psychosocial factors found
      were the absence of another adult at home, unemployment, and history of drug
      abuse among the perpetrators.

PMID- 7583736
TI  - Whatever happened on the way to counselling? Hurdles in the interagency
      environment.
AB  - A study of confirmed cases of child sexual abuse showed that only 56% of children
      received an appointment at a counselling agency in spite of explicit policy
      guidelines that children have an opportunity for counselling in the aftermath of
      the abuse. The study revealed that problems created at all levels within the
      interagency environment led to children becoming "lost" in the system and not
      receiving the services from which they could have benefited. Particular attention
      is given to changes in the broader policy and resource context which have
      ramifications at the local interagency level and in the services provided for
      sexually abused children.

PMID- 7583737
TI  - Sibling incest offenders.
AB  - Sibling incest is the least investigated but probably the most common form of
      incest. This study describes a predominantly Caucasian, middle-income sample of
      sibling incest offenders from primarily intact families. Demographics, behavioral
      dysfunction, psychiatric diagnoses, history of victimization, family
      characteristics, and abuse characteristics are presented. Findings included that
      92% of the offenders had a history of being physically abused, whereas only 8%
      had a history of sexual victimization. Issues of parental denial and minimization
      and intergenerational transmission of abusive patterns are discussed. Sibling
      incest demands further attention from clinicians and researchers.

PMID- 7583738
TI  - Serum dopamine beta hydroxylase and maltreatment in psychiatrically hospitalized
      boys.
AB  - Fifty boys, hospitalized on a school-age and an adolescent unit in an
      intermediate length psychiatric hospital, were studied while off psychoactive
      medication to determine how serum dopamine beta hydroxylase (DBH) activity varies
      with different childhood maltreatment experiences. Childhood maltreatment was
      categorized according to onset (before 36 months old, between 36-72 months old
      and over 72 months old). Childhood maltreatment groups were compared with a group
      of psychiatrically hospitalized boys who had neither been abused nor neglected.
      Boys who were younger than 72 months at age of onset of maltreatment had
      significantly lower DBH activity than those who had experienced maltreatment
      later in childhood and those who had not been subjected to abuse or neglect. This
      difference appeared attributable to the DBH activity of school age (but not
      adolescent) boys who had been abused/neglected before 72 months. Boys with a
      principal diagnosis of conduct disorder solitary aggressive type had lower DBH
      activity than boys without this diagnosis regardless of whether or not they had
      been maltreated. Low serum DBH may be a biological sequela of maltreatment early
      in life that correlates with the development of conduct disorder solitary
      aggressive type in boys.

PMID- 7583739
TI  - Benzodiazepine administration induces exogenic psychosis: a case of child abuse.
AB  - An 11-year-old boy with psychiatric symptoms was brought to the pediatric clinic
      by his father. The boy exhibited anxiety, sometimes exaggerating to panic
      reactions, rage, and disorientation. Because of the boy's behavior it was
      presumed he was having delusions. Careful physical examination revealed evidence
      of physical abuse. This article alerts readers to the possible combination of
      physical abuse and purposeful drug administration.

PMID- 7583741
TI  - Commentary: the review of child maltreatment fatalities: snatching victory from
      the jaws of defeat.

PMID- 7583740
TI  - Pattern of intentional burns to children in Ghana.
AB  - Intentional (inflicted) injury to children through burns has been studied and
      mentioned extensively in the literature, although much less so in developing
      countries. A community-based survey of children aged 0-5 years in the Ashanti
      Region of Ghana found that of 650 childhood burns, 35 (5.4%) were purposefully
      inflicted. The perpetrators were mostly friends (43%) and siblings (37%) of the
      victims, and traditional healers (6%) who inflicted these burns to children who
      were comatose after convulsions. Intentional burns were more likely to be
      inflicted by flame (OR = 3.87, 95% CI = 1.52-10.0), and contact with a hot object
      (OR = 1.66, 95% CI = .62-4.44) than through scalding, the most common cause of
      burns in this region. Other patterns of intentional burns included the absence of
      any adult, burns covering < 3-5% of body surface area, and increased rate of
      wound infection. These findings contrast with the pattern of intentional burns
      seen in other countries, notably developed ones. Even though these inflicted
      burns were minor, it is important that doctors working in this setting become
      aware of their presence and that traditional healers and the general public be
      educated about the appropriate treatment for childhood convulsions.

PMID- 7583744
TI  - Child fatalities in Scottish house fires 1980-1990: a case of child neglect?
AB  - This paper considers 168 child (< 17 years) fatalities killed in house fires in
      Scotland. Data were obtained from the records retained by the procurators fiscal,
      as part of a survey into all Scottish fire fatalities during the period 1980 to
      1990. Although these fires were generally perceived as being tragic "accidents,"
      we conclude that they were largely a direct result of the activities of adults in
      the home. We analyze this in terms of contemporaneous supervision and the child
      care environment. The role of alcohol in domestic fires is particularly
      important. Behavioral patterns of parents and caregivers are seen to be placing
      children in a very high risk category and fatality rate could be significantly
      reduced if behavior was modified to reduce the risk. Whether these considerations
      imply "neglect" is partly a question of definition. It is important to recognize
      that the fire safety message could usefully be integrated within a more general
      child care or family welfare scheme. Front line professionals in these fields are
      ideally placed to convey this message and to make a contribution towards reducing
      the risk of children being killed or injured in fire.

PMID- 7583743
TI  - Understanding fatal child abuse.
AB  - Medical, social service and coroner reports were reviewed for 14 cases of fatal
      child abuse and neglect identified at a children's hospital from 1988-1992.
      Twelve cases involved physical abuse and two neglect. The median age was 6.5
      months (range 24 days to 3 years). Six families (43%) had prior protective
      service involvement; however, four of the referrals involved a sibling. Only two
      of 12 physical abuse victims had a history of a prior suspicious injury. Clinical
      and postmortem findings are presented. The cause of death in all physically
      abused patients was blunt impact head injury; one also had contributing
      intraabdominal injuries. Ten cases were ruled due to homicide; 12 have come to
      legal closure resulting in nine felony convictions. These findings emphasize the
      role of blunt impact brain injury in fatal child abuse cases. Two findings have
      significant implications for prevention: (a) the paucity of injuries recognized
      prior to the fatal event, and (b) among families known to child protection
      agencies the focus was not the fatally injured child.

PMID- 7583742
TI  - Childhood deaths from physical abuse.
AB  - This paper gives a detailed account of 30 cases of childhood deaths caused by
      physical abuse, detected by the Suspected Child Abuse and Neglect (SCAN) team,
      General Hospital, Kuala Lumpur. They consisted of 12 Malays, 6 Chinese, 9 Indian,
      and 1 Indonesian child. Three cases could not be ascertained as to their ethnic
      origin. There were 13 male and 17 female children. The average age of the abused
      children was 2 years 5 months. The most frequent causes of death were
      intracranial hemorrhage and intraabdominal trauma. Of the 17 cases of
      intracranial hemorrhage, only four had X-ray evidence of skull fracture. This
      suggests the possibility of whiplash injuries with/without the abuser suspecting
      that he/she had injured the child. Of the 22 abusers who could be identified,
      there was no sex differentiation. Fathers formed the largest group of
      perpetrators, followed by mothers and childminders. Fifteen of the natural
      parents of the abused children were married, four were divorced and four were
      never married. Five of the abusers had aggressive personalities and three were
      drug addicts. Only one abuser was found to be an alcoholic even though a few were
      also under suspicion. For most cases, trigger factors could not be identified.

PMID- 7583747
TI  - Seminar on child abuse.

PMID- 7583746
TI  - Estimating the occurrence of child maltreatment and risk-factor effects: benefits
      of a mixed-design strategy in epidemiologic research.
AB  - Despite the large volume of literature on child abuse and neglect generated over
      the past two decades, there has been relatively little comprehensive discussion
      of the limitations of different study designs for achieving major epidemiologic
      research goals. Although some improvements have been made in conventional
      research designs, there have been few efforts to develop new approaches. This
      article discusses the methodologic limitations of four observational study
      designs--ecologic, case-control, cross-sectional, and cohort--that dominate the
      child abuse and neglect literature; identifies key features of an "ideal" study
      of child maltreatment; and proposes a new mixed-design research strategy. The
      major advantage of the proposed strategy is that it greatly improves the ability
      to identify cases of child maltreatment from a well-defined population at risk
      representing diverse segments of the US population.

PMID- 7583745
TI  - Fatalities assessed by the Orange County child death review team, 1989 to 1991.
AB  - Interagency child death review teams have emerged in response to the increasing
      awareness of severe violence perpetrated against children in the United States.
      Child death review involves a systematic, multidisciplinary, and multiagency
      process to coordinate data and resources from the coroner, law enforcement, the
      courts, child protective services, and health care providers. The Orange County,
      CA team reviews all coroner's cases (unattended death or questionable cause of
      death) for children 12 years old and younger. This paper describes the
      interagency review in Orange County and provides data on the demographics of
      cases reviewed by the team (N = 637) compared to unreviewed deaths (N = 1,463)
      for the period 1989 to 1991. Trends were analyzed to assess differences in: (1)
      age distribution; (2) gender; (3) ethnicity; (4) cause of death (non-SIDS
      natural; non-natural including traffic deaths, SIDS, other injuries; homicide;
      and undetermined); and (5) cause of death by age, gender, and ethnicity.
      Implications of the data for other jurisdictions with child death review teams
      are discussed.

PMID- 7583748
TI  - Neglectful mothers, their mothers, and partners: the significance of mutual aid.
AB  - Those who work to prevent the conditions that lead to child neglect need to know
      which supportive resources parents lack and why. The goals of this paper are to:
      (a) determine if mothers who neglect their children exchange (i.e., give and
      receive) fewer resources with two network members: their mothers and partners;
      and (b) identify a set of relationship characteristics that create barriers to
      the receipt of resources. Sixty-nine neglectful mothers were compared to a
      demographically comparable sample of 138 mothers. The results support the
      conclusion that neglectful mothers exchange fewer resources with both their
      partners and mothers, but the deficit varied depending on the network member and
      the type of support. Several additional relationship characteristics
      differentiated neglectful mothers from comparison mothers. Neglectful mothers
      were more likely to state their mothers had fewer positive attributes (e.g., was
      not warm and caring), their relationship was less positive, and they were less
      interested in receiving resources from their mothers. Partners of neglectful and
      comparison mothers did not differ on any of these characteristics. Instead,
      neglectful mothers and their partners knew each other for less time, were likely
      to be living with each other, and saw each other less frequently.

PMID- 7583749
TI  - Client and worker satisfaction in a child protection agency.
AB  - Client and staff satisfaction with the workings of a multidisciplinary child
      protection agency were investigated using interviews and standard questionnaires.
      The goal was to discover the nature and strength of the helping relationship
      between service-recipients and providers. Current clients (N = 24) expressed a
      great deal of satisfaction with the staff and services. The agency staff (N = 21,
      with 11 employed at least half-time to work directly with families) were
      relatively satisfied with their jobs, and showed little evidence of the burnout
      which has been recognized as a risk for child protection workers. They were able
      to relate empathically to clients and felt enthusiasm for the work. Taking
      account of possible bias in both sets of answers, there is still evidence that
      the agency is succeeding in creating a necessary precondition for therapeutic
      change: the development of accepting and positive worker-client relationships.

PMID- 7583751
TI  - The impact of a media campaign on public action to help maltreated children in
      addictive families.
AB  - Developed because of the need to promote public understanding of the link between
      addictions and child maltreatment, a multimedia campaign helped to increase by
      62% the average monthly number of people who called a telephone service for
      information about how to aid abused and neglected children. The campaign was
      supported by market research and professional experience that indicated the
      campaign should focus on easy action a citizen could take, avoid inducing fear or
      blame, and target third party helpers and younger families-at-risk. Campaign
      exposure was promoted through the support of corporate partners. A random
      household survey found that 61% of the general population had seen or heard the
      campaign slogan. The average monthly calls to the child maltreatment information
      service regarding alcohol and other drug abuse tripled and the requests regarding
      at-risk children almost doubled. An auxiliary project provided interprofessional
      education to increase the probability that people seeking help would get it when
      referrals were made. The project yielded several lessons for future public
      awareness campaigns: focus on helping action rather than the problem; use of
      client-based market research; a strategic plan to assure necessary exposure;
      reliance on public-private-nonprofit sector partnerships; preparation of the
      service system; promotion of personal ways of helping.

PMID- 7583750
TI  - Childhood maltreatment, childhood social support, and child abuse potential in a
      Basque sample.
AB  - The present study obtained data on childhood physical and sexual abuse in a
      Basque sample in order to compare abuse rates with a similar study conducted in
      the United States. The study also examined the relationships between childhood
      physical and sexual abuse, childhood social support, and abuse potential in the
      Basque sample. Although the overall rates of physically abusive behaviors were
      similar in the Basque and US samples, the rates of physical abuse sequelae
      (bruises/welts, cuts/scratches, dislocations, burns, and/or bone fractures) were
      lower in the Basque sample. In addition, while the rates of sexual abuse were
      similar for females, the sexual abuse rates for Basque males were more than
      double the rates reported for US males. As expected, a childhood history of
      physical and sexual abuse were directly related to child abuse potential.
      Childhood social support, especially father support, was inversely associated
      with abuse potential. An interaction between a childhood history of physical
      abuse and father support was found where those with a history of abuse and low
      levels of father support had the highest level of abuse potential and those with
      a history of abuse and high levels of father support had the lowest level of
      abuse potential.

PMID- 7583752
TI  - A study of the variability of training and beliefs among professionals who
      interview children to investigate suspected sexual abuse.
AB  - The study aimed to examine the relationship between professional background,
      number of qualifications, specific training in child sexual abuse and beliefs
      about indicators of child sexual abuse in professionals who conduct sexual abuse
      investigatory interviews. A questionnaire was sent to all professionals within a
      discrete geographical area who were involved in the investigation of child sexual
      abuse. One hundred and six of 136 questionnaires were returned (77.9%), 60 of
      which were from investigatory interviewers. The latter comprised eight different
      professions. There was a considerable variation in general training and in
      training in child sexual abuse specifically, both of which were more likely to
      have been received by medical psychological and social work respondents than
      residential care workers and police officers. Beliefs about sexual abuse
      indicators showed a striking variation between respondents. Most of the variation
      was not accounted for by the respondent variables examined. Where there was
      evidence for an association, the interviewer's professional background had the
      strongest effect, followed by the number of qualifications and the number of
      investigatory interviews conducted per year. Previous training in child sexual
      abuse had no significant effect on these beliefs. Further research is needed into
      the optimal training necessary for members of different professions in order to
      change their beliefs about child sexual abuse.

PMID- 7583754
TI  - Assessing juvenile sex offenders to determine adequate levels of supervision.
AB  - The present study analyzed the internal consistency of four inventories currently
      being used by probation officers in the state of Utah to determine adequate and
      efficacious supervision levels and placement for juvenile sex offenders. The
      internal consistency or reliability of the inventories ranged from moderate to
      good. Factor analysis was utilized to significantly increase the reliability of
      the four inventories by collapsing them into the following three factors: (a)
      Custodian's and Juvenile's Attitude Toward Intervention; (b) Offense
      Characteristics; and (c) Historical Risk Factors. These three inventories/factors
      explained 41.2% of the variance in the combined inventories' scores. Suggestions
      are made regarding the creation of an additional inventory. "Characteristics of
      the Victim" to account for more of the variance. In addition, suggestions as to
      how these inventories can be used by probation officers to make objective and
      consistent decisions about adequate supervision levels and placement for juvenile
      sex offenders are discussed.

PMID- 7583753
TI  - Impact of patient history on residents' evaluation on child sexual abuse.
AB  - OBJECTIVE: To determine if historical information influences residents'
      interpretation of physical findings in sexually abused children. METHODOLOGY: In
      a pediatric residency training program, all residents viewed 15 slides of
      children's genitalia (8 normal, 7 abnormal) with either a history specific for
      sexual abuse or one which was nonspecific. Three weeks later the same slides were
      viewed but with the alternate history scenario. The residents were asked if the
      physical findings were specific for sexual abuse. RESULTS: Sixty-four percent of
      residents completed both surveys. Correct response rate did not vary by gender or
      year of training. Responses were most often correct when the slide and history
      were normal (87%). Responses were least accurate when normal historical
      information was presented with abnormal slides (49%). A logistic regression model
      demonstrated that residents were less accurate when history and physical did not
      agree (95% CI = .54- .78). Reexamination of the data using areas under the
      Receiver Operating Characteristic (ROC) curve confirmed that residents performed
      on a less accurate ROC curve when the slide and history were incongruent (p <
      .01). CONCLUSION: Incongruency between patient history and physical exam findings
      negatively affected this group of residents' ability to discriminate between
      abuse and nonabuse findings.

PMID- 7583755
TI  - Characteristics of child sexual abuse victims according to perpetrator gender.
AB  - Characteristics of child sexual abuse victims were determined through a
      comparison of 87 victims of lone female perpetrators to 93 victims of lone male
      perpetrators according to age, gender, and relationship of perpetrator to the
      victim. Lone female perpetrators abused children 3.3 years younger (M = 6.0
      years) than lone male perpetrators (M = 9.3 years). Both lone female and lone
      male perpetrators abused more girls (62%, 76%, respectively) than boys. Female
      perpetrators were more likely to be caretakers than male perpetrators, whereas
      male perpetrators were more likely to be strangers than female perpetrators.
      Lastly, lone female perpetrators, lone male perpetrators, and male/female
      coperpetrators did not differ regarding severity of abuse. Thus, contrary to
      popular assumption, abuse by female perpetrators was not less severe than abuse
      by male perpetrators.

PMID- 7583756
TI  - Psychological sequelae in adult females reporting childhood ritualistic abuse.
AB  - The present study sought to increase current scientific knowledge about the
      controversial issue of subjectively reported childhood ritualistic abuse by
      addressing several key unresolved issues. In particular, the possibility that
      those reporting ritualistic abuse may be characterized primarily by the severity
      of their abuse histories or the severity of their present psychological symptoms,
      rather than the veridicality of the ritualistic events, was explored. Adult
      female outpatients reporting childhood sexual abuse with ritualistic features
      were compared with a second group of women who reported childhood sexual abuse
      without ritualism. Measures included characteristics of childhood sexual and
      physical abuse, current posttraumatic stress disorder (PTSD) diagnostic status
      and symptom severity, and severity of current dissociative experiences. Women
      reporting ritualistic features scored significantly higher on measures of
      childhood sexual and physical abuse. Neither PTSD diagnostic status nor severity
      for PTSD nor dissociative experiences were significantly different between the
      groups. While preliminary in nature, these results suggest that it may be helpful
      to conceptualize reported childhood ritualistic abuse as indicative of the need
      to assess carefully for severe abuse and its predictable sequelae within existing
      traumatic victimization conceptual frameworks.

PMID- 7583757
TI  - Sexually abused and nonabused mothers' discussions about sex and their children's
      sexual knowledge.
AB  - This study investigated the impact of a mother's experience of childhood sexual
      abuse on her discussion of sex with her child. Two groups of sexually abused and
      nonabused mothers, drawn from a larger community sample and matched for social
      class and the sex and age of their index children, were asked about discussion of
      sexual information within their family. Children were interviewed about their
      sexual knowledge. Significantly more mothers who reported an incident of sexual
      abuse during their childhood said that they had detailed discussions with their
      child about sexual development and contraception than mothers who reported no
      childhood incidence of abuse. Although there was no difference between the two
      groups in independent interviewers' ratings of the children's overall sexual
      knowledge, more children from the abused mothers' group mentioned their parents
      as a definite source of sexual information, in particular, regarding
      contraception. There were also differences between the two groups in the
      children's responses to a set of ambiguous pictures. More children in the abused
      mothers' group than the nonabused group gave stories related to child abductions
      and the possibility of sexual abuse in response to two of the pictures. A
      mothers' willingness to acknowledge childhood sexual abuse is related to more
      open discussion of sexual information within the family.

PMID- 7583760
TI  - Biodiversity and its molecular foundation [.

PMID- 7583758
TI  - Children's anticipation of and response to colposcopic examination.
AB  - Just prior to and following general physical and colposcopic anogenital exams, 43
      mothers and daughters (3-15 years), referred because of allegations of sexual
      abuse, were interviewed separately to determine their knowledge of and feelings
      about the exam. Children were not retraumatized by the examination of their
      anogenital anatomy. Although poorly prepared for it, children reported medical
      staff touch to their genitals, anus, and buttocks at a higher rate than touch to
      all other body locations, 84.5% versus 16%, but did not rate that touch as more
      painful. Children were significantly less distressed after the exam; mothers were
      not.

PMID- 7583759
TI  - [XXth Congress of the Society of Biomechanics. Lausanne, Switzerland, 11-12
      September 1995. Abstracts].

PMID- 7583761
TI  - A C4HC3 zinc finger motif.
AB  - Metal-binding cysteine and histidine residues are often used to stabilise a
      protein fold through coordination of zinc ions. These zinc fingers are either
      involved in nucleic acid binding (TFIIIA, GAL4, nuclear receptors, retroviral
      gag...) or in yet unidentified biochemical functions (LIM and RING domains). The
      latter characterized by a unique histidine residue in the zinc binding motif
      (C2HC5 and C3HC4 for the LIM and RING respectively) may constitute
      protein/protein interaction interfaces. We have identified a new C4HC3 motif in a
      variety of proteins including the Drosophila trithorax and its human homologue
      ALL-1 involved in oncogenic translocations in acute leukaemias. This domain, for
      which we propose the name TTC (for trithorax consensus) is found in many
      transcriptional regulators or DNA-binding proteins. Interestingly, TTC was found
      in several bromodomain containing transcriptional adaptors including the E1A
      binding p300 and the CREB-binding CBP proteins. In CBP, this domain does not
      appear to be involved in DNA, CREB or TFIIB binding. In the chromosomal
      translocations that involve the 11q23 locus, the C-terminal end of ALL-1 (which
      contains 4 TTC fingers) is constantly lost. The absence of these motifs in the
      fusion genes may relate to their leukemogenic potential.

PMID- 7583763
TI  - Olfactory learning and memory in the honeybee: comparison of different classical
      conditioning procedures of the proboscis extension response.
AB  - Olfactory learning in the honeybee was investigated using the conditioned
      proboscis extension reflex on restrained individuals. We compared, under the same
      experimental conditions, the most commonly used conditioning procedures, i.e. 1
      trial, 3 massed trials (1 min inter-trial intervals), and 3 spaced trials (10 min
      inter-trial intervals) procedures, using linalool as the conditioned stimulus.
      Two experiments were performed in which worker bees were subjected to: (1) a
      single test at different times (30 s to 14 days) after the conditioning
      procedure; (2) a first test within 3 h after the conditioning procedure, and were
      then retested daily (up to 5 tests). The memory trace of a learnt odorant
      stimulus could last for the lifetime of the bee, even after a single association
      with sugar. Repeated tests with 1 day inter-test duration induced a strong
      decrease of the response level, this effect being more pronounced after a 1-trial
      conditioning.

PMID- 7583762
TI  - Immunocytochemical characterization of Tau proteins during cerebral aging of the
      lemurian primate Microcebus murinus.
AB  - The immunocytochemistry of Tau proteins in the cortical pyramidal neurons of the
      adult microcebes has been studied, using antibodies against human normal and
      pathological Tau proteins. Some changes related to the age and to some
      pathologies were observed. In fact, during the adult life, Tau proteins appeared
      as very thin granulations scattered in the whole neuronal cytoplasm. With age, a
      part of these proteins aggregated and became like thick granules at the neuron
      periphery; the distribution was not uniform, and numerous neurons with aggregated
      Tau proteins were observed in amyloid plaque-containing brains. Abnormally
      phosphorylated Tau proteins were also observed in some aged animals, using an
      absorbed anti-PHF recognizing the pathological Tau proteins characteristic of
      Alzheimer's disease. This present work confirms that the microcebe is a good
      model for studying disfunctions involved in the normal cerebral aging and in some
      neurodegenerative disorders which affect humans.

PMID- 7583764
TI  - [Effects of hydrostatic pressure on malondialdehyde (MDA) determination in brain
      from yellow freshwater eels].
AB  - Malondialdehyde (MDA) content in a tissue can be an indicator of lipoperoxidation
      and thus of membrane alteration. MDA concentrations have been measured in the
      brain of yellow freshwater eels (Anguilla anguilla) submitted to 1.51 or 101 ATA
      of hydrostatic pressure. Exposure to pressure was performed for 6 h at constant
      water temperature and in normoxic conditions. The results thus obtained show a
      significant increase (P < 0.05 or better) of MDA brain concentrations at 51 ATA
      (+ 124%) and 101 ATA (+ 290%). These results mean that hydrostatic pressure is
      able to activate lipoperoxidation and can alter membrane functions together with
      the decrease in membrane fluidity it induces. Such a membrane alteration can
      explain, at least in part, the excitation periods which are observed during and
      after animal compression.

PMID- 7583765
TI  - Factors regulating megakaryocyte progenitor commitment to polyploidization.
AB  - Recognizable megakaryocytes are polyploid cells generated by a clonogenic,
      diploid progenitor, termed CFU-MKC (colony forming unit, megakaryocyte). In order
      to quantify polyploidization, ploidy histograms of megakaryocytes determined by
      microphotometric or flow cytometric measurements of megakaryocyte DNA have
      generally been used. However these techniques provide no information on the rate
      of commitment of CFU-MKC to polyploidy. Using a technique of clonal analysis
      determining the distributions of the number of doublings (NbD) undergone by CFU
      MKC before committing to polyploidization, the polyploidization probability of
      CFU-MKC could be derived. This probability was found to be a constant independent
      from CFU-MKC mitotic history, since NbD distributions are exponential functions
      characterized by a constant rate of decay per doubling. By studying the effects
      of growth factors on polyploidization probability, it was also shown that: (1)
      this parameter is negatively regulated by growth factors contained in poke-weed
      or WEHI conditioned media, as well as by erythropoietin; (2) commitment to
      polyploidization does not require prior CFU-MKC division; (3) bipotent erythroid
      megakaryocyte progenitors have a lower polyploidization probability than CFU-MKC;
      (4) determination of polyploidization probability reflects the activity of growth
      factors with greater accuracy than megakaryocyte colony count.

PMID- 7583766
TI  - Interaction of 2 amino acid substitutions within the same beta chain of human
      hemoglobin: the examples of Hb Corbeil and Hb Villeparisis.
AB  - Only 16 hemoglobin (Hb) variants carrying 2 point mutations within the same
      polypeptide chain have been identified up to now. Two of those are reported in
      this paper. In Hb Villeparisis, the beta 77 (EF1) His-->Tyr mutation is identical
      to that of Hb Fukuyama while the other mutation, beta 80 (EF4) Asn-->Ser, has not
      yet been described. These 2 abnormalities are located almost within interacting
      distance. They lead to decreased oxygen affinity and, according to molecular
      simulations, to a remodeling of the surface of the molecule. Hb Corbeil
      associates 2 substitutions, that of Hb E [beta 26 (B8) Glu-->Lys], and of Hb
      Sherwood Forest [beta 104 (G6) Arg-->Thr], which are far from one another. The
      resulting properties consist only in the additive effects of both abnormalities.
      Hb Corbeil is, thus, a thalassemic Hb, like Hb E, and a molecule having altered
      oxygen binding properties, characterized by decreased heterotropic effects,
      similar to those of Hb Sherwood Forest. The simultaneous presence of more than 1
      structural abnormality leads to a large spectrum of possible consequences on the
      function of the molecule, from local effects to a perturbation of intermolecular
      interactions. The genetic mechanism resulting in Hb with more than 1 point
      mutation is discussed: in some cases it is very likely that the second mutation
      arose on a chromosome already carrying a point mutation, in contrast a single
      mutational event involving a micro gene conversion has been proposed in other
      cases.

PMID- 7583767
TI  - [Identification of spermatozoa L-selectin and two potential pellucida ligands].
AB  - At the molecular level, gamete interactions partly depend on zona pellucida
      glycoproteins fucosylation. We show, by immunocytochemistry, the sialyl-lewisx
      and sialyl-lewisa oligosaccharides on human zonae pellucidae. These epitopes are
      potential ligands of cell adhesion molecules named selectins which are known to
      play a role in endothelium-leukocyte interactions. By immunofluorescence, we find
      the leukocyte selectin (L-selectin) on the spermatozoa head. Preincubation of
      spermatozoa with an anti-L-selectin monoclonal antibody produces a significant
      inhibition of zona pellucida tight binding, under hemizona assay conditions. In
      contrast, preincubation of the zonae pellucidae with anti-sialyl-lewisx or anti
      sialyl-lewisa antibodies does not produce a significant inhibition of spermatozoa
      binding. Western blot analysis of spermatozoa-detergent extracts revealed a band
      at approximatively 90 kDa with the anti-L-selectin monoclonal antibody. This
      spermatozoa selectin could play a role in human spermatozoa-zona pellucida
      binding. Zona-ligands have yet to be precisely defined.

PMID- 7583769
TI  - [Paleoparasitology: presumption of a case with bilharzia of the 15th century at
      Montbeliard (Doubs, France)].
AB  - On the archeological site of Montbeliard, paleoparasitological and
      sedimentological analysis of cesspit deposits led to the detection of well
      preserved parasitological forms (remains of helminths with associated eggs). The
      morphology and morphometry of these forms point to a plausible case of bilharzia
      transmitted by Schistosoma haematobium. The chance of ancient or recent
      contamination of the sample is discussed.

PMID- 7583768
TI  - A rare allele of a microsatellite located in the tyrosine hydroxylase gene found
      in schizophrenic patients.
AB  - We investigated the frequency of a rare variant of a common microsatellite
      tetrarepeat allele in the tyrosine hydroxylase gene in 2 independent ethnic
      groups of schizophrenic patients and their matched controls. In a French
      population we found the rare variant allele in 5 of 94 (5%) unrelated chronic
      schizophrenic patients and in none of 145 unaffected controls, thus yielding a
      significant association (p < 0.01) between schizophrenia and the tyrosine
      hydroxylase gene. Similarly, in a replication study, we found the rare allele in
      4 of 44 (9%) unrelated chronic schizophrenic patients and in none of 44
      unaffected controls in a Tunisian population. Albeit the reason of this
      association is at the moment unknown, it is possible that this polymorphism in
      the tyrosine hydroxylase gene may be involved in the regulation of its activity.

PMID- 7583770
TI  - [HLA-G: a non classical antigen of major histocompatibility complex].

PMID- 7583771
TI  - From collagen type I solution to fibers with a helical pattern: a self-assembly
      phenomenon.
AB  - To determine whether collagen solubilized from tendons can regenerate the most
      relevant characteristics of the tendon supraorganization was the aim of the
      present study. Extracted and purified collagen in acetic acid solutions subjected
      to precipitation and extensive dialysis was found to produce gels with
      rheological properties that allowed them to form threads and rubber-like rods.
      Molecular order and the ordered aggregational state of the fibers were detected
      by optical anisotropy at the polarization microscope. Self-assembly and self
      organization resulted in a supraorganized structure in which the fibers are
      ordered parallel to the long axis of the thread or the rod, and in an intertwined
      helical organization. The highly birefringent fibers and their geometrically
      ordered self-organization resembled the original tendons. Some questions related
      to morphogenesis, recognition and adhesion events, biomechanical properties of
      collagen-containing structures and development of biomaterial for medical use may
      be answered by this model. In terms of perspectives it would be important to
      consider collagen fibers as models for producing organic-inorganic interface
      depositions to achieve optical properties.

PMID- 7583772
TI  - [Alternative transcripts of the MHC of the non-classical class I HLA-G gene in
      the in trophoblast during the first pregnancy trimester and in the placenta at
      term].
AB  - HLA-G, a non-classical class I gene, is located within the human major
      histocompatibility complex locus. It has a tissue-specific expression in
      trophoblast, where the products of HLA-A, -B and -C classical genes are absent.
      Therefore, the HLA-G gene may have a role during pregnancy in inducing protection
      of the semi-allogeneic fetus from recognition and destruction by maternal immune
      cells. The primary transcript of the HLA-G gene is alternatively spliced into 6
      mRNA forms (HLA-G1 to HLA-G6), 2 of them may encode soluble forms of the HLA-G
      antigen (HLA-G5 and HLA-G6). In this work, by using reverse transcription
      polymerase chain reaction technique, we demonstrate that all transcripts are
      detected in similar amounts, both in the first and third trimester of gestation.
      These results are discussed in context of putative function of HLA-G antigen
      isoforms.

PMID- 7583773
TI  - [Modifications of the olfactory bulb electrocorticogram and trans-glomerular
      evoked potentials in staggerer mutant mice].
AB  - Electrophysiological observations have been made on normal C57-BL/6J and
      staggerer mutant mice. Morphological observations have given evidence it existed
      various neurones modifications which affected the olfactory bulb in the mutant
      mice. Olfactory bulb electrocorticograms (ECoG) of mutant have shown rare bursts
      of potentials of longer time duration than in normal mice. These bursts were less
      affected by odor stimulations (ammonia and urine of opposite sexes) than in the
      normal mice and never varied under urine odor influence in female mutant. Evoked
      potential induced by the odors had long latency and long duration (up to 50 ms vs
      30 ms). In a large amount of them, the late phases and the late oscillatory
      potentials, which generally followed the evoked potential, were absent. All these
      results improved the idea that staggerer mutation, which mainly affected the N
      CAM gene, not only induced cerebellar diseases, but also functionally affects the
      olfactory bulb.

PMID- 7583776
TI  - [Heart rate fluctuations in the horse at rest: (2) Biological variation factors
      related to behavioural profile].
AB  - Variability of heart rate was analysed within a sample of 30 horses in order to
      determine the influence of factors (animal, age, sex and breed) associated with
      different behavioural patterns. The heart rate fluctuations were analysed by
      computing the power spectral density of a series of heartbeat intervals. A
      generalized linear model was used to compare the spectra and to reveal the effect
      of each factor: animal age, sex and breed. The scale and shape of spectral
      densities were significantly different between animals. This individual
      variability was partly explained by the sex and age effects while the breed
      effect had only a weak influence. Young horses and mares exhibited a greater
      heart rate fluctuation which may be related to their higher emotionality.

PMID- 7583775
TI  - [Heart rate fluctuations in the horse at rest: (1) Investigation of heart rate
      changes by spectrum analysis].
AB  - The heart rate fluctuations at rest were studied in order to explore the
      emotionality of the horses by isolating the influence of the autonomic control.
      This paper presents a method of spectral analysis which was used to analyse the
      heart rate variability in the frequency domain. The heartbeat intervals were
      recorded during 1 h and a series of 1,024 heartbeats was extracted to compute a
      power spectrum of density. This was obtained by calculating the Fourier transform
      of the autocorrelation function of the series. This spectral analysis was applied
      to heart rate recordings in order to illustrate its sensitivity. The normal heart
      rate fluctuations at rest were compared with those obtained after atropine and
      atropine+adrenaline injections. The normal power spectrum revealed several low
      frequency components (< 0.1 cycle/beat). The atropine injection reduced heart
      rate variability while the atropine+adrenaline injection increased the power of
      low frequency fluctuations.

PMID- 7583774
TI  - Differential expression of somatostatin receptors by quantitative PCR in the rat
      brain.
AB  - Five subtypes of somatostatin receptors (sst) have recently been cloned and
      reported to be expressed in rat brain. However, conventional mRNA measurement
      techniques do not allow to accurately compare the levels of expression of the 5
      sst. Thus, we established a quantitative reverse transcriptase polymerase chain
      reaction method for the 5 sst. A cRNA internal standard was constructed by
      inserting in msst1 plasmid sequences corresponding to specific sense primers for
      amplification of each sst. Using a common reverse primer, a unique primer pair by
      receptor amplifies both wild type and standard RNAs with the same efficiency. The
      technique was validated by evaluating sst mRNAs in 3 brain structures in which
      different somatostatin receptor binding levels were previously reported. While
      the absolute level of expression is similar between regions, sst3 is the major
      subtype in cerebellum, sst1 predominates in spinal cord and sst4 and sst2 are
      equally expressed in the hypothalamus.

PMID- 7583777
TI  - Cyclosporin A promotes nuclear transfer of a cytoplasmic progesterone receptor
      mutant.
AB  - The effects of cyclosporin A (CsA), FK506 and rapamycin (Rapa) on the
      intracellular localization of a mutated rabbit progesterone receptor (PR) which
      lacks the main constitutive nuclear localization signal (NLS) (delta 638-642) and
      is cytoplasmic in the absence of progesterone (Prog), were assayed by indirect
      immunofluorescence in Lcl3 cells, a mouse L-cell line stably expressing this
      mutant. CsA alone, at 5-10 microM concentrations, induced almost complete nuclear
      transfer of the PR-mutant within 18 h. In contrast, FK506 and Rapa at the same
      concentrations had no effect. This nuclear transfer induced by CsA was
      concentration and time dependent and was independent of protein synthesis. It was
      not a potentiation of hormone action since it took place in the absence of
      hormone, including in serum-free culture conditions. The implications of this
      specific effect of CsA are discussed.

PMID- 7583778
TI  - Readjusting the localization of long QT syndrome gene on chromosome 11p15.
AB  - Long QT syndrome (LQT) is an autosomal dominant cardiac disease characterized by
      ventricular arrhythmia. A first locus for LQT has been identified on chromosome
      11p15.5 (LQT1), closely linked to HRAS. To refine the location of LQT1,
      microsatellites were genotyped in 8 French families and the following order was
      determined: tel-HRAS-DRD4-D11S922-D11S4046- IGF2-INS-TH-D11S1318-D11S1323
      D11S1338-D11S90 9-D11S1346-cen. By haplotype analysis, 12 crossing-over events
      were identified in affected and unaffected subjects, delineating the LQT1
      candidate region to 7 cM. This new delineated localization between D11S1318 and
      D11S1323 is in a more centromeric region than previously thought and is 5 cM
      proximal to HRAS.

PMID- 7583779
TI  - Managed care and health information networks.
AB  - Communication and data exchange among existing health information systems is
      becoming increasingly important in the health care industry. In a managed care
      environment, the focus is on delivering value by providing consumers access to
      high-quality health care at reasonable cost. This article explains how the use of
      a health information network in the managed care system, which links all related
      entities, improves the quality of health care by allowing access to critical data
      on demand and decreases the cost of delivery by enhancing communication among
      managed care providers.

PMID- 7583780
TI  - Assessing the quality of primary care: the use and importance of reimbursement
      data.
AB  - Although inpatient quality assessment efforts have advanced greatly in recent
      years, similar growth has not yet been experienced in ambulatory care. However,
      given the growth of primary care and its role in managed care systems, the need
      for quality assessment innovations is great and the future looks promising. The
      authors describe their experience in developing such an innovation in an
      ambulatory care setting. The goal of this article is to identify and describe how
      secondary data--in particular, data from reimbursement systems--may be used to
      develop a primary care quality of care assessment system. This investigation
      highlights the importance of reimbursement data in developing clinically
      meaningful and practical models for quality assessment.

PMID- 7583781
TI  - The availability of health care information for consumer use.
AB  - This study assesses the current availability of health care cost and quality
      information at both the state and national levels. More than 130 sources were
      contacted, including all state commissioners of health and state hospital
      associations. Eighty-one percent of the responding states report provider
      specific information to the public, 73% require providers to submit data to the
      state, and the department of health or a state health care commission is the data
      collection entity of 69% of the states. However ambitious or mature some state
      health care data initiatives have become, the comparative measures of provider
      performance are generally primitive, the data sources are unreliable in many
      cases, and the data sources and measures are widely variant across states.

PMID- 7583783
TI  - Academic medical centers and the fight for survival in the new era of managed
      care.
AB  - This article reviews the threatened state of academic medical centers in the new
      era of managed care. Particular emphasis is given to the onslaught of capitation
      and risk sharing. Related strategies of quality enhancement, system development,
      and cost reduction are also discussed.

PMID- 7583784
TI  - The use of relational databases in health care information systems.
AB  - The relational database is especially well suited to be the cornerstone of the
      next generation of health care information systems. Health care organizations can
      take advantage of the lessons learned from major corporations that have built
      entire information infrastructures using it. The relational model's strength in
      handling the analysis of transaction data makes it ideal for fulfilling complex
      utilization review requirements and providing a solid foundation for the
      increasing operational demands of large physician-managed managed care networks.

PMID- 7583782
TI  - Managed care organizations and confidential patient information: the need for a
      uniform standard.
AB  - There is a lack of comprehensive implementation of a cognizable national standard
      regarding use of confidential patient information by managed care organizations.
      As such, it is difficult for a managed care organization to balance the goal of
      demonstrating its quality and efficiency with the necessity of maintaining a
      patient's right to confidentiality of medical records, and in so doing, avoid or
      at least limit exposure to liability for violating that right.

PMID- 7583785
TI  - Capital financing along the integration highway.
AB  - In the process of reshaping the entire nation's health care delivery system, it
      is only natural that financing vehicles which we once considered "standard" are
      evolving as well. The purpose of this article is to explore some of the creative
      and nontraditional vehicles available to emerging health care organizations and
      integrated systems to access capital. This brief overview focuses on the
      organizational structures, financial characteristics, and financial structures of
      emerging health care delivery networks and providers. Select case studies provide
      examples of the more creative financial structures currently being employed to
      meet rapidly growing fund needs.

PMID- 7583786
TI  - Hospital indigent care expenditures.
AB  - The Georgia State Health Planning Agency provided financial information for 144
      general hospitals for the year 1992. Not-for-profit hospitals do not appear to
      fund charity care to a greater degree than for-profit hospitals. Uninsured
      patients in Georgia do not appear to use emergency department services instead of
      a primary care physician. Patient behavior may be influenced by the fact that
      many public health departments offer free primary care.

PMID- 7583787
TI  - Nematode development is inhibited by methyl viologen and high oxygen
      concentrations at a rate inversely proportional to life span.
AB  - Eight strains of C. elegans, including seven recombinant inbred (RI) strains with
      mean life spans ranging from 10.9 to 28.8 days, were reared under two conditions
      (95% oxygen or methyl viologen) known to elevate the concentration of free
      radicals. Both agents inhibited development, as ascertained by measuring the
      lengths of animals at regular intervals. The degree of inhibition correlated
      inversely with mean life span with both agents; that is, development of short
      lived strains was inhibited more profoundly than was development of long-lived
      strains. Thus, at least some of the polygenes which prominently influence aging
      are the same as those which control resistance to free radicals. These genes
      likely influence aging and response to oxidative stress in many ways, both direct
      and indirect.

PMID- 7583788
TI  - Lipofuscin as a record of "rate of living" in an aquatic poikilotherm.
AB  - As an integral of oxidative metabolism and physiological age index, lipofuscin
      accumulation was used to evaluate assumptions underlying previous rejection of
      the rate of living theory of aging. Lipofuscin in the olfactory lobe cell mass of
      crayfish, Cherax quadricarinatus, was measured throughout life under a wide range
      of temperature regimes, using image analysis of fluorescence micrographs of brain
      sections. The relationship between temperature, chronological age, and rate of
      living, as indicated by lipofuscin accumulation rate, had a complex nonlinear
      three-dimensional structure, suggesting a thermal optimum, thermal mid-range
      metabolic compensation, and age-associated variation. The particular experimental
      window through which this response surface is viewed will have a profound effect
      on the outcome of life span experiments such as those previously used to test the
      rate of living theory. The results of this study further challenge assumptions
      leading to previous rejection of this theory.

PMID- 7583789
TI  - Caloric restriction decreases age-dependent accumulation of the glycoxidation
      products, N epsilon-(carboxymethyl)lysine and pentosidine, in rat skin collagen.
AB  - Nonenzymatic glycation of body proteins and subsequent advanced glycation
      reactions have been implicated in the aging process, while caloric restriction
      (CR) in rodents results in an increase in both mean and maximum life span. We
      have evaluated the effect of chronic (25 months) CR on glycation of blood
      proteins and accumulation of advanced glycation and oxidation (glycoxidation)
      products, N epsilon-(carboxymethyl)lysine (CML), and pentosidine, in skin
      collagen. Brown-Norway rats, fed ad libitum (AL) from birth, were divided into
      two equal groups at 4 months of age and placed on AL or CR diets (CR = 60% of AL
      diet). Cohorts of animals were sacrificed at 7, 13, and 25 months after the
      initiation of CR. At necropsy glycated hemoglobin was measured by affinity HPLC
      and glycated plasma protein by the fructosamine assay; extracts of skin collagen
      were analyzed by gas chromatography-mass spectrometry for CML and by reversed
      phase HPLC for pentosidine. Glycation of hemoglobin, plasma proteins, and skin
      collagen was decreased significantly (18-33%) by CR. Concentrations of CML and
      pentosidine increased significantly with age in skin collagen in both AL and CR
      animals; however, CR significantly reduced levels of CML (25%), pentosidine
      (50%), and fluorescence (15%) in collagen in the oldest rats. We conclude that CR
      reduces the extent of glycation of blood and tissue proteins and the age-related
      accumulation of glycoxidation products in skin collagen.

PMID- 7583790
TI  - GnRH receptor site increase on the surface of cultured gonadotropes of senescent
      C57BL/6NNia mice.
AB  - Anterior pituitary cells were cultured for 2 days from 6-, 14-, and 23-25-month
      old C57BL/6NNia mice. The cells were then stimulated with one of three
      biotinylated GnRHs [biotinyl-Lys6]-[D-Lys6]GnRH, [biotinyl-Ser4]-[D-Lys6]GnRH,
      [biotinyl-Ser4]-[D-Trp6, des-Gly10]GnRH) at 4 degrees C for 1 h. Some of these
      cells were processed unfixed, attaching avidin-fluorescein and examined with
      fluorescent microscopy. Other cells were fixed and the biotinylated GnRH coupled
      to avidin-gold (20 nm particles), which was subsequently silver-enhanced (70 nm
      particles) and examined with light and scanning electron microscopy (SEM). To
      enhance the location of receptor sites for quantitation, a back-scattering
      electron detector was employed with the SEM. Gonadotropes from all three age
      groups ranged in size from 3 to 13 microns in diameter. The largest gonadotropes
      in each age group displayed the highest number of GnRH receptors, but the
      concentration/surface area (microns2) was less than for smaller cells. Smaller
      gonadotropes (3-6 microns diameter) from 14- and 23-25-month-old mice contained
      more GnRH receptor sites/microns2 (p < .001) than those from 6-month-old mice;
      the percentage of these gonadotropes was markedly higher for 14-(65%) and 25
      (52%) versus 6-month-old (5%) mice. The number of receptor sites in larger
      gonadotropes (6.1-13 microns diameter) did not decline with the increasing age of
      the mouse. Decreased secretory activity in gonadotropes of 25-month-old mice may
      result from age-related changes in pituitary peptide processing or release, but
      it is not due to a lack of GnRH receptors or the inability of GnRH to bind to its
      receptor site.

PMID- 7583791
TI  - Age-related effects in rabbit hearts of N6-R-phenylisopropyladenosine, an
      adenosine A1 receptor agonist.
AB  - Interventions known to increase cytoplasmic Ca2+ appear to amplify age-related
      impairment of cardiac function. In addition, increased release of interstitial
      adenosine, an endogenous nucleoside, has been suggested to mediate the diminished
      beta-adrenergic responsiveness in senescent heart. However, the direct effects of
      adenosine A1 receptor activation on senescent myocardium have not been
      investigated thoroughly. Therefore, the effects of N6-R-phenylisopropyladenosine
      (R-PIA), an A1 agonist, on atrial rate and contractility (+dF/dt) in adult (6-8
      months) and senescent (5-7 years) New Zealand White rabbits were compared in
      spontaneously beating right atria and electrically stimulated isolated right
      papillary muscles. Although senescent right atria appeared to be more sensitive
      to the negative chronotropic-effects of R-PIA, the effective concentrations
      producing 50% of the maximum response (EC50 values) of R-PIA were not
      significantly different between adult (26 nM, 95% confidence limits: 12-52 nM)
      and senescent (13 nM; 95% confidence limits: 10-16 nM). However, senescent right
      ventricular papillary muscles were more sensitive to the negative inotropic
      effects of R-PIA. For example, at 90 contractions/min, 100 nM R-PIA decreased
      +dF/dt 25.3 +/- 7.4% and 61.9 +/- 4.8% in adult and senescent papillary muscles,
      respectively. To investigate whether R-PIA might alter sarcoplasmic reticulum
      (SR) function as a mechanism of decreased inotropy, we determined the inotropic
      effects of R-PIA on steady-state and 30-s postrest-potentiated contractions (PRP;
      an index of SR Ca2+ release) of left atria. R-PIA did not selectively decrease
      contractility of PRP compared to steady state in either adult or senescent left
      atria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583792
TI  - Age-related changes in cardiac norepinephrine release: role of calcium movement.
AB  - The purpose of this study was to determine if the age-related decrease in
      norepinephrine (NE) release from cardiac adrenergic nerve terminals is due to a
      defect in Ca2+ movement into the nerve terminal or to an alteration in Ca2+
      activation of intracellular events leading to NE release. NE release was assessed
      in cardiac synaptosomes prepared from 6- and 24-month-old male F344 rats. K(+)
      induced NE release was significantly greater in young vs old rats. Raising
      extracellular [Ca2+] increased NE release, but NE release always remained higher
      in the younger animals. Ionomycin, a Ca2+ ionophore, induced NE release from
      cardiac synaptosomes, and there was no age difference in the response. The age
      related reduction in NE release induced by K+ and the capacity of ionomycin to
      induce similar NE release in young and old cardiac synaptosomes points to a
      reduction in Ca2+ movement during depolarization.

PMID- 7583793
TI  - Diminished cell-cell binding by lymphocytes from healthy, elderly humans:
      evidence for altered activation of LFA-1 function with age.
AB  - We studied the kinetics of cell-cell adhesion by monocyte-depleted peripheral
      blood lymphocytes with a stirred-cuvette aggregometer using samples from healthy
      young (mean age = 25 years) and healthy elderly (mean age = 75 years) human
      donors. This was a very reproducible assay, as there was virtually no
      intraindividual variability and very little interindividual variability among
      donors of the same age group. In all cases, aggregation of cells began
      immediately upon addition of the protein kinase C activator phorbol myristate
      acetate (PMA) or the calcium ionophore ionomycin, and continued until reaching an
      asymptotic limit by 20 minutes or less. Unstimulated cells did not aggregate
      during this time. The rate of aggregate formation and total amount of aggregation
      (using young donors' cells) varied between PMA- and ionomycin-stimulated cells,
      suggesting different mechanisms for initiating cellular aggregation, or possibly,
      different peripheral blood lymphocyte subsets affected by these activating
      agents. However, for both stimuli, the rate of aggregation and the total amount
      of cellular aggregation were significantly lower with the elderly donors' cells.
      Further, aggregation was Ca2+/Mg2+ dependent, and the reaction required
      metabolically active cells, as the reaction was inhibited by the addition of
      sodium azide and 2-deoxy-D-glucose in both donor groups. Pretreating cells with
      the actin polymerization inhibitor cytochalasin B resulted in 35-40% inhibition
      of aggregation among young donors' cells, although, interestingly, there was no
      apparent effect upon the cells capable of forming aggregates in the old donor
      group. In both donor groups, aggregation by activated cells could be partially
      blocked by pretreating cells with monoclonal antibodies directed against the
      alpha and beta chains of the integrin leukocyte function-associated antigen-1
      (LFA-1) (CD11a/CD18). These results show that there is diminished cell-cell
      binding among lymphocytes from healthy, elderly humans, and this is partly due to
      altered activation of LFA-1 function with age.

PMID- 7583794
TI  - Immune parameters in a longitudinal study of a very old population of Swedish
      people: a comparison between survivors and nonsurvivors.
AB  - As a part of an ongoing longitudinal investigation, this study examined
      relationships between survival and selected immune system parameters in a sample
      (n = 102) of very old individuals (86-92 years at the time of initial immune
      system data collection). Analyses were performed comparing initial time-point
      measurements from those individuals who were alive (n = 75) and those who were
      deceased (n = 27) two years after initial data collection. Immune system
      measurements consisted of determination of peripheral blood lymphocytes and
      lymphocyte subsets, as well as T-cell responses to activation by Concanavalin A.
      Cluster analysis identified a subgroup associated with nonsurvival which
      indicated characteristics that included: poor T-cell proliferative responses,
      high CD8 percentages, and low CD4 and CD19 percentages. This multivariate
      analysis suggested that combinations of immune system parameters predict two-year
      survival otherwise not apparent when single immune system parameters were
      evaluated in the elderly.

PMID- 7583795
TI  - Altered switch in lipid composition during T-cell blast transformation in the
      healthy elderly.
AB  - Decreased mitogen responsiveness of lymphocytes during aging correlates inversely
      with membrane microviscosity, which reflects an altered lipid composition.
      Therefore, we addressed the question, whether age-related alterations of lipid
      metabolism affect the switch in lipid composition during formation of blasts.
      Membrane lipids and fatty acids of peripheral blood lymphocytes from SENIEUR
      protocol compatible ("healthy") elderly donors (66-77 yr) and young controls (18
      30 yr) were quantified after incubation with or without the mitogen
      phytohaemagglutinin. The blastic change in membrane lipid composition was
      different for young controls with respect to cholesterol,
      phosphatidylethanolamine, total phospholipids, as well as several fatty acids.
      Moreover, the age-related alterations in the switch of membrane lipids and fatty
      acids were significantly correlated with a decreased mitogen response. Thus, the
      alterations in membrane reorganization during blast formation of lymphocytes from
      the elderly point to a disturbed cellular lipid homeostasis with possible impact
      on the age-related reduction in immune function.

PMID- 7583796
TI  - Time course of hypertrophic adaptations of the anterior latissimus dorsi muscle
      to stretch overload in aged Japanese quail.
AB  - The purpose of this study was to determine if aged Japanese quail demonstrated an
      altered time course of change in the morphology of the anterior latissimus dorsi
      (ALD) muscle during the first two weeks of hypertrophy induced by stretch
      overload. The left wing of adult (12 weeks of age) and aged (90 weeks of age)
      birds were weighted with 10% of their body weight; the right wing served as the
      intra-animal control. Thirteen to sixteen birds from each age group were killed
      after 7 and 14 days of stretch overload. Total fiber number was quantified by
      counting all the fibers in a transverse section from the mid-belly of the ALD
      muscle. The aged ALD retained the ability to increase the mass and total fiber
      number of the stretched ALD after 7 (82%, 16%) and 14 (102%, 19%) days of stretch
      overload. However, there was a main effect of age on the capacity to increase
      muscle mass and total fiber number after stretch overload. These results suggest
      that aging diminishes the increase and alters the time course of adaptation in
      fiber number and myofibrillar mass of the stretch overloaded ALD during the first
      two weeks of stretch overload.

PMID- 7583797
TI  - The influence of aging on muscle strength and muscle fiber characteristics with
      special reference to eccentric strength.
AB  - It is well established that aging seriously reduces isometric and concentric
      muscle strength due to atrophy, deterioration of mechanical properties, and motor
      unit loss. However, there is limited information on the impact of aging on
      eccentric strength despite the fact that such forces play an equally important
      role during daily activities. The purpose of this study was to examine the
      influence of aging on three expressions of muscle strength (isometric,
      concentric, and eccentric) in relation to muscle fiber characteristics, with
      special emphasis on eccentric force. Sedentary but healthy men (age range 18-80
      years, n = 60) and women (20-74 years, n = 30) were tested for maximal effort
      isometric, concentric, and eccentric (1.05, 2.09, 3.14 rads.s-1) quadriceps
      strength, body composition, and muscle fiber characteristics of the vastus
      lateralis (men only). There was a significant (p < .05) approximately 30 N per
      decade decline in isometric and concentric forces, but only 9 N per decade
      reduction in eccentric strength. There was a significant reduction in Type II
      muscle fiber area with aging (p < .05). Isometric, eccentric, and concentric
      force correlated r = .33, r = .32 (p < .05), and r = .12 (p > .05) with Type II
      muscle fiber area, respectively. The correlation between age and fat-free
      mass/force ratio ranged from r = .39 to .43 in men and r = .27 to .50 in women.
      The data suggest a relative preservation of eccentric strength with aging in men
      and women that seems to be independent of muscle mass or muscle fiber type or
      size.

PMID- 7583798
TI  - Food odor thresholds in relation to age, nutritional, and health status.
AB  - Odor perception plays an important role in nutrition. In the present study, the
      effect of aging and health status on detection of food odors is shown and
      interrelations with nutritional status are explored. We have tested 26 healthy
      young (20-25 yrs) and 23 elderly (61-74 yrs) subjects who were screened according
      to the SENIEUR protocol. Anthropometric measures and blood samples provided 20
      parameters of nutritional status. A validated measurement procedure under forced
      choice conditions was used to quantify the detection thresholds of two food odors
      of which one had a trigeminal effect and the other mainly had an olfactory
      effect. There is a significant declining sensitivity for both odors. Our
      observations indicate that a relation between nutrition and odor perception in
      the elderly population exists. Whether olfactory deficits cause or are caused by
      increased nutritional risk deserves further study.

PMID- 7583799
TI  - A cross-sectional validation study of the FICSIT common data base static balance
      measures. Frailty and Injuries: Cooperative Studies of Intervention Techniques.
AB  - BACKGROUND: Two simple balance scales comprising three or four familiar tests of
      static balance were developed, and their validity and reliability are described.
      The scales were such that the relative difficulties of the basic tests were taken
      into consideration. METHODS: Using FICSIT data, Fisher's method was used to
      construct scales combining ability to maintain balance in parallel, semi-tandem,
      tandem, and one-legged stances. Reliability was inferred from the stability of
      the measure over 3-4 months. Construct validity was assessed by cross-sectional
      correlations. RESULTS: Test-retest reliability (over 3-4 months) was good (r =
      .66). Validity of the FICSIT-3 scale was suggested by its low correlation with
      age, its moderate to high correlations with physical function measures, and three
      balance assessment systems. The FICSIT-4 scale discriminated balance over a wide
      range of health status; the three-test scale had a substantial ceiling effect in
      community samples. CONCLUSION: A balance scale was developed that appears to have
      acceptable reliability, validity, and discriminant ability.

PMID- 7583800
TI  - Classification trees for decision making in long-term care.
AB  - BACKGROUND: The purpose of the study was to develop a classification tool
      predicting a requirement for nursing home care in a population of nursing home
      applicants. In long-term care services, the objectives of classification
      mechanisms will include the prevention of inappropriate nursing home admission.
      METHOD: We studied 295 nursing home applicants residing in the Lower North Shore
      Area of Sydney, a high socioeconomic status area of Sydney, Australia. The
      predictor variables examined included: demographic data, social work assessment
      data, the presence of dementia and incontinence, the Barthel Index of Activities
      of Daily Living, and the Mini-Mental State Examination. RESULTS: Classification
      analysis using the C4.5 Program resulted in several classification trees for a
      decision for nursing home care with sensitivities greater than 70%. The best
      classification tree was one which combined the scores of the Barthel Index and
      the Mini-Mental State Examination. CONCLUSION: Classification trees in their
      simplicity of design and application have advantages over other analytical
      methods of classification. Classification analysis and the trees examined in this
      study may have future useful application in decision making for long-term care.

PMID- 7583801
TI  - Observed sleep/wakefulness and severity of dementia in an Alzheimer's disease
      special care unit.
AB  - BACKGROUND: This study tested the hypothesis that behaviorally defined sleep
      disturbance among residents in a Special Care Unit (SCU) for Alzheimer's disease
      (AD) was related to the severity of their dementia. Previously, sleep laboratory
      studies have reported such relationships when sleep has been recorded
      polysomnographically over several nights. Observational studies of sleep have not
      shown such relationships, presumably because of the impression involved in
      determining sleep/wake state behaviorally. METHODS: Nightly sleep data based on
      observations made every two hours by nursing staff for a period of 13 to 18
      months were examined for 47 AD residents with a mean age of 80.7 +/- 6.5 years.
      Level of dementia and functional capacity were assessed with the Mattis Dementia
      Rating Scale (DRS) and the Katz Activities of Daily Living Scale (ADL). RESULTS:
      Data indicated that these SCU residents experienced a moderately disturbed night
      of sleep an average of 24% +/- 10% of their nights in the facility and a severely
      disturbed night of sleep on 7% +/- 6% of those nights. More profound dementia was
      associated with more sleep disturbance; however, incapacity in ADLs, age, gender,
      and psychoactive medications were unrelated to such disturbances. CONCLUSIONS:
      The results indicate that patterns of relationships noted between laboratory
      based measures of sleep and variables such as severity of dementia can be
      detected using behavioral observations of sleep, provided that the number of
      nights of observation are sufficiently large to offset the measurement error
      involved in their use.

PMID- 7583802
TI  - Cross-sectional age differences in body composition in persons 60+ years of age.
AB  - BACKGROUND: There is little information for age differences in body composition
      in elderly people > 65 years of age, especially for those > 80 years. As the
      proportion of people older than 65 years is expected to nearly double during the
      next few decades, this information is needed. METHODS: Age differences in body
      composition and anthropometry were examined in 316 men and women aged 60 to 95
      years. Multiple components of body composition were quantified using dual energy
      X-ray absorptiometry and isotope dilution methods, and expressed in molecular and
      cellular models. Analysis of variance was used to test for differences between
      age groups 60 to 70, 71 to 80, and > 80 years in each sex. Body composition
      components were regressed on age, controlling for knee height, fat-free mass, or
      total body fat. Age-adjusted correlations were calculated with anthropometric
      variables. RESULTS: Fat-free mass (FFM), body cell mass (BCM), and appendicular
      skeletal muscle (ASM) decreased with age in both sexes. ASM decreased relative to
      FFM in both the men and the women, while BCM decreased relative to FFM in the
      women only. Total fat mass and percent body fat decreased with age in the women,
      but not in the men. Body fat distribution did not appear to change with age.
      Anthropometric indices, muscle area and waist/hip ratio, had low correlations
      with muscle mass and fat distribution. CONCLUSIONS: "Sarcopenia," or muscle loss,
      continues to occur into old age, and may have significant impacts on physical
      function and health status. New anthropometric techniques are needed for
      assessing muscle loss with age.

PMID- 7583803
TI  - Interrelationships of peak expiratory flow rate with physical and cognitive
      function in the elderly: MacArthur Foundation studies of aging.
AB  - BACKGROUND: Peak expiratory flow rate (PEFR) is correlated with several measures
      of health in the elderly, including physical and cognitive function. It is
      unclear, however, whether these relationships persist among the non-frail.
      METHODS: The Community-based Studies of the MacArthur Foundation Research Network
      on Successful Aging included measures of PEFR using a mini-Wright peak flow meter
      on a sample of 1,354 subjects selected from those aged 70-79 in three population
      samples. Subjects were chosen on the basis of simple measures of physical and
      cognitive function (high = 1192; medium = 80; low = 82), and were given a series
      of more detailed tests. RESULTS: Residual PEFR, adjusted for age, sex, height,
      weight, and smoking, was highly correlated (p < .001) with several physical
      performance measures, including number of steps in a tandem walk, number of
      seconds in a single leg stand, times to turn in a circle, write one's name, and
      walk 10 feet at a fast pace, foot-tapping (time per tap), and hand grip strength.
      The strongest association was evident for a combination of six physical function
      items. Residual PEFR was also correlated with cognitive performance, including
      tests of similarities, naming, spatial recognition, memory, and figure drawing.
      The strongest association was present for a combined measure. These associations
      persisted in analyses restricted to those in the "high" function group as well as
      with no history of previous myocardial infarction, stroke, or cancer. Residual
      PEFR also exhibited a strong independent association with urinary norepinephrine,
      as measured in 12-hour overnight urine specimens. This relation did not appear to
      be mediated by smoking or medication use.

PMID- 7583805
TI  - Treatment of hepatitis C virus in elderly persons with interferon alpha.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a health problem that is common in adults.
      Because screening of blood and blood products for HCV has only been possible
      recently, older adults are more likely than younger adults to have HCV. Despite
      the higher prevalence of HCV in older adults, few are treated. This failure to
      treat is a result of the concern that the untoward effects of Interferon alpha
      (IFN) may not be tolerable in older individuals. METHODS: Twenty-five subjects
      age > 65 years who were Ab-HCV positive and desired IFN therapy were treated with
      5 MU Interferon administered TIW for 6 months. Twenty-five adults (mean age 44 +/
      1 years) matched for gender and histologic disease were utilized as a control
      population. Responses were classified as full if the ALT level was normal, and
      partial if the ALT fell by > 50% but was still abnormal after 6 months of
      therapy. All other responses were defined as failures. RESULTS: At the end of
      treatment, no biochemical difference between the elderly and younger adults was
      evident for any parameter. Moreover, the response rates (48% and 41%,
      respectively) were nearly identical. None of the elderly discontinued IFN therapy
      during the treatment period. The rate of untoward events reported by the elderly
      was similar to that reported by the younger controls. CONCLUSIONS: These data
      demonstrate that: (a) the elderly with HCV infections can be treated with IFN;
      (b) the response rate is similar in elderly and younger adults; and, (c) the rate
      and type of untoward IFN effects experienced by the elderly do not differ from
      that reported by younger adults.

PMID- 7583804
TI  - Hormonal responses in elders experiencing pre-syncopal symptoms during head-up
      tilt before and after exercise training.
AB  - BACKGROUND: Hormonal responses of elderly individuals experiencing pre-syncopal
      symptoms during head-up tilt testing (HUT) were compared with responses of
      nonsymptomatic subjects both before (T1) and after (T2) 6 months of endurance
      training. METHODS: Based on responses to HUT at T1, 35 men and women (ages 61-79
      years) were placed into symptomatic and nonsymptomatic groups for analysis.
      Symptomatic subjects (n = 5) experienced lightheadedness, nausea, sweating, or
      syncope during T1 HUT but completed 15 minutes of HUT at T2. Training consisted
      of treadmill walking or stairclimbing 3 x/wk, 30-45 min/day, at 75-85% of maximal
      heart rate reserve. Adrenocorticotropic hormone (ACTH), vasopressin, aldosterone,
      norepinephrine, epinephrine, hemoglobin, and hematocrit were measured during
      supine rest prior to HUT, and either at the end of the 15-minute HUT or at
      symptom onset. Plasma volume (PV) was measured at supine rest; tilt-induced
      changes in PV were calculated from changes in hemoglobin and hematocrit. RESULTS:
      During T1 HUT, symptomatic subjects had greater increases in vasopressin and a
      greater rate of PV loss (p < .05). Increases in ACTH and aldosterone were greater
      in symptomatic subjects at T1 and T2, while increases in norepinephrine were
      greater at T2 (p < .05). Reductions in tilt-induced vasopressin concentration and
      a decreased rate of PV loss were seen at T2 in symptomatic subjects. CONCLUSIONS:
      T1 results from symptomatic subjects are consistent with greater stimulation of
      volume-sensitive receptors induced by a greater rate of fall in PV. Exercise
      training resulted in increased tilt tolerance for symptomatic subjects associated
      with reductions in vasopressin concentration and rate of PV loss during tilt.

PMID- 7583807
TI  - Psychological obstacles to job or career change in late life.
AB  - Four studies involving middle-aged and older workers were conducted to (a)
      explore perceived obstacles to adaptive job or career changes in later-life, and
      (b) develop an instrument with which to identify older adults who might be more
      sensitive to such obstacles. A reliable instrument was developed which reflected
      three broad categories of perceived risk: (a) age-inappropriateness of the
      change, (b) potential for age-discrimination, and (c) risk of hastened
      obsolescence. As evidence for the convergent validity of the instrument, the
      results indicated a heightened sensitivity to job change obstacles among
      respondents with: (a) age-sensitized concerns about job and financial security,
      (b) poorer psychological adjustment to a plateaued career, and (c) poorer
      psychological and social adjustment to their own aging.

PMID- 7583808
TI  - The effects of cognitive impairment on 9-year mortality in a community sample.
AB  - Using 9-year mortality data on a community sample of 3,560 adults aged 40 and
      over, this study assessed the effects of cognitive functioning and one-year
      declines in cognitive functioning on mortality controlling for comorbid chronic
      medical illness, physical disability, and psychiatric illness. The study
      determined the 9-year vital status and, among the decreased, date of death of
      respondents who were first interviewed in 1980 by the New Haven Epidemiologic
      Catchment Area Study. Mortality risk by cognitive functioning, as assessed by the
      Mini-Mental State Examination (MMSE), was estimated using Cox Proportional
      Hazards Models controlling for baseline assessments of physical and mental
      health. For both men and women, lower scores on the MMSE decreased the risk of
      survival, although the effect was stronger for younger respondents than older
      respondents. Decline in MMSE scores over the course of one year had no additional
      effect on mortality beyond the resulting MMSE score. Cause-specific mortality was
      also examined.

PMID- 7583809
TI  - Aging, inhibition, working memory, and speed.
AB  - An implication of the hypothesis that failures of inhibition contribution to
      adult age differences in working memory (Hasher & Zacks, 1988) is that
      statistical control of measures of inhibition should reduce the age-related
      effects on working memory. This implication was tested in a study in which
      interference measures from three variants of a Stroop task served as the measures
      of inhibition. Although the age-related variance in measures of working memory
      was substantially reduced after control of the interference measures, the degree
      of attenuation was at least as large when speed measures from other tasks were
      controlled. Furthermore, additional analysis revealed that speed measures from
      tasks requiring oral, written, and keypress responses shared large proportions of
      their age-related variance. It was suggested that age-related influences on
      specific processes, such as inhibition, cannot be accurately assessed unless the
      contributions of more general age-related influences are taken into
      consideration.

PMID- 7583806
TI  - Metabolic and hormonal changes induced by hypodermoclysis of glucose-saline
      solution in elderly patients.
AB  - BACKGROUND: Hypodermoclysis, i.e., infusion of solutions into the subcutaneous
      tissues, is an alternative method for hydration. The aim of our study was to
      describe the metabolic changes induced by hypodermoclysis of a glucose-saline
      solution in elderly patients. METHODS: Twelve experiments were conducted in a
      random cross-over study, intravenous infusion (IV) vs subcutaneous infusion (SC),
      in 6 hospitalized patients (81.5 +/- 9.8 years). The solution (1000 mL of 5%
      glucose solution containing 4 g NaCl) was infused over 6 hours in fasted patients
      who remained in bed. Blood was sampled at -10, 0, 30, 60, 90, 120, 180, 240, 300,
      and 360 minutes for measurement of plasma concentrations of glucose, insulin,
      free fatty acids, and beta-hydroxybutyrate. Plasma concentration of cortisol was
      analyzed only at T-10, T0, T180, and T360. RESULTS: The increases in glucose and
      insulin and the decrease in plasma concentrations of free fatty acids were lower
      with SC infusion than with IV infusion. The decrease in beta-hydroxybutyrate
      plasma concentration was lower at T300 with SC infusion than with IV infusion.
      The decrease in cortisol did not differ with the route. Plasma concentrations of
      all compounds were similar at T360. CONCLUSION: We conclude that hypodermoclysis
      of glucose-saline solution induced similar but smaller metabolic and hormonal
      changes than the IV infusion.

PMID- 7583810
TI  - A longitudinal study of Off-Target Verbosity.
AB  - This study reports a follow-up examination of the speech of 175 subjects, aged 65
      and over, who had participated in an initial evaluation of the cognitive and
      psychosocial correlates of Off-Target Verbosity (OTV). OTV speech showed
      significant stability across the 15 months of the study. The pattern of
      relationships among age, cognitive function, psychosocial variables, and OTV
      scores was similar for the two test occasions. Subjects who had experienced more
      frequent and less desirable life changes and had lower verbal fluency scores were
      more verbose. An association between age and OTV appeared due to age-related
      inhibition and psychosocial functioning. The results were interpreted within a
      conceptual model framework illustrating causal and other links among variables.

PMID- 7583811
TI  - Age changes in the distribution of visual attention.
AB  - Two experiments examined adult age differences in the controlled allocation of
      visual selective attention. Both experiments were identical with the exception of
      the stimulus display where targets and distractors were linearly increased with
      eccentricity in Experiment 2. A spatial cuing task was used with four cue-target
      presentation intervals (SOAs) of 250, 500, 1000, and 2000 msec (Experiment 1) and
      250, 500, 750, and 1000 msec (Experiment 2). Results were fit to three
      quantitative models based on attentional distribution metaphors (spotlight, zoom
      lens, and ring) in order to determine the best fitting model of attentional
      distribution. Data from Experiment 1 indicated that older subjects distributed
      attention in a qualitatively different manner than younger subjects and suggested
      a different time course of processing. When stimuli visibility was controlled a
      single flexible resource allocation (ring) model of attention could account for
      the results of both age groups at all SOAs. Results further suggested that older
      adults employ compensatory strategies to offset visual processing difficulties.

PMID- 7583812
TI  - What have we "made" of aging?

PMID- 7583813
TI  - Self-ratings of health: do they also predict change in functional ability?
AB  - Self-ratings of health by individuals responding to surveys have shown themselves
      to be potent predictors of mortality in a growing number of studies; they appear
      to contribute significant additional independent information to health status
      indicators gathered through self-reported health histories or medical
      examinations. A key question raised by these studies is: What are the mediating
      processes involved in the association? Specifically, do poor self-ratings
      increase the risk of disability and morbidity, and are these outcomes intervening
      steps in the link to mortality? In this report we address the first question, of
      self-ratings predicting future levels of functional disability, our choice of an
      index of overall impact of morbidity. Data come from the New Haven Established
      Populations for Epidemiologic Studies of the Elderly (EPESE) site (N = 2,812).
      Results show that self-ratings of health in 1982, net of baseline functional
      ability, health and sociodemographic status, are associated with changes in
      functional ability over periods of one through six years. These findings extend
      our understanding of the meaning of excellent, good, fair, and poor ratings of
      health, and that they have implications not just for survival but for the loss or
      maintenance of functional ability in daily life.

PMID- 7583815
TI  - Women's caregiving: changing profiles and pathways.
AB  - This study draws on panel data from a random sample of 293 wives and mothers,
      interviewed in 1956 and 1986, to: (1) examine changes in women's caregiving
      experiences across four different birth cohorts, and (2) assess the likelihood of
      women becoming caregivers. Women born in the late 1920s and early 1930s reported
      more episodes of caring for members of an older generation, for disabled
      children, and for more than one person at a time than women born prior to 1926.
      The percentage of women with two or more episodes of caregiving increases
      significantly from the earliest (born 1905-1917) to the most recent cohort (born
      1927-1934). Using event history analysis, we tested the effects of social
      structural variables and subjective dispositions, as well as the number,
      duration, and timing of competing roles, on the likelihood of women becoming
      caregivers. We find that women with more traditional life styles are more likely
      to become caregivers; however, potentially competing roles, such as employment,
      do not seem to decrease, and actually are positively related to, the likelihood
      of caregiving. To consider various pathways to caregiving, we also conduct
      subgroup analyses by cohort and educational level.

PMID- 7583814
TI  - Social support, depression, and recovery of walking ability following hip
      fracture surgery.
AB  - The importance of social support and depression to recovery from illness is
      examined with reference to hip fracture. Subjects were community-dwelling,
      ambulatory White females 59 years of age and over who were recovering from hip
      fracture surgery. The respondents were interviewed at baseline and clinically
      interviewed 2 and 6 months postsurgery. Inadequacy of social support and
      depression resulted in less improvement in walking ability at 2 months. By 6
      months, the flow of casual influence was in the reverse direction, with low
      improvement in walking ability leading to increased level of depression. Social
      support's influence mediated the impact of health and background factors, but
      this was primarily at 2 months. If social support is to influence recovery, it
      must be present early in the recovery process. Social support's long-term
      consequences are indirectly operating through recovery measures taken shortly
      after the illness event.

PMID- 7583816
TI  - Race, control, mastery, and caregiver distress.
AB  - This study investigated the relationship between race, psychological resources of
      sense of control and caregiver mastery, and distress outcomes of caregiver
      depression and role stain among 77 African American and 138 White spouse
      caregivers of persons with dementia. Patterns of association between
      psychological resources and caregiving distress outcomes varied by type of
      outcome. Sense of control had a direct negative relationship with depression.
      Caregiver mastery moderated the effects of stressors on depression and was the
      only significant psychological resource predicting role strain. Although African
      American caregivers were less likely to report caregiver depression and role
      strain, there were no race differences in the process influencing caregiver
      distress.

PMID- 7583817
TI  - Transitions in functional status and active life expectancy among older people in
      Japan.
AB  - This study analyzes the patterns and determinants of the transitions in
      functional status among elderly Japanese persons. Data for this research came
      from a two-wave national probability sample survey of persons aged 60 and over
      conducted between 1987 and 1990 in Japan. The study focuses on the transitions
      from two states of origin, "not disable" and "disabled," to three states of
      destination, "not disabled," "disabled," and "dead." Through multinomial logit
      analyses, the effects of sociodemographic factors, social relationships, health,
      and health behavior on transitions in functional status were examined. To assess
      the impact of panel attrition, the risk of nonresponse was analyzed in
      conjunction with health transition within the same framework. Finally, an
      increment-decrement active life table for Japanese elderly people was derived on
      the basis of the multivariate analyses. According to the life table, a Japanese
      older person at age 60 is expected to spend about 18.7 years (81%) in functional
      independence and about 4.4 years (19%) in disability throughout his or her
      remaining lifetime.

PMID- 7583818
TI  - Motive and the geographic mobility of very old Americans.
AB  - The proposition that motives for migration are important in explaining geographic
      mobility of very old persons was explored in this study. Data from the biennial
      1984 through 1990 rounds of the Longitudinal Study on Aging were used to predict
      the move/not-move behavior of a nationally representative sample of
      noninstitutionalized respondents aged 70 years and over in 1984. Six motives for
      elderly migration were identified: health, affiliation, economic security,
      comfort, functional independence, and getting on with life after family crisis.
      When incorporated within this motivational framework, reason-for-move data showed
      that health was not the dominant motive; responses were divided among the five
      other motive categories. The logistic regression analysis showed that increasing
      disability was positively related to mobility for respondents in only one of six
      motive categories. The results suggest that a motive-for-migration perspective
      broadens the debate on types of, and explanations for, migration behavior of
      noninstitutionalized very old Americans.

PMID- 7583820
TI  - Second proton-pump inhibitor marketed.

PMID- 7583819
TI  - Study assigns dollar value to alteplase-streptokinase debate.

PMID- 7583822
TI  - Obtaining prescribing authority for pharmacists: lessons learned.

PMID- 7583823
TI  - Requirements for pharmacists dispensing ephedrine products.

PMID- 7583821
TI  - Adenosine approved for use in stress testing.

PMID- 7583824
TI  - Videotapes for staff training.

PMID- 7583825
TI  - Pharmacist prescribing.

PMID- 7583826
TI  - Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors.
AB  - Drug-drug, drug-food, and drug-disease interactions involving
      hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are reviewed. The
      four available HMG-CoA reductase inhibitors-lovastatin, simvastatin, pravastatin,
      and fluvastatin-have different potentials for drug interactions, probably because
      of their different pharmacokinetic characteristics. Interactions of some of these
      cholesterol-lowering agents with cyclosporine, erythromycin, high-dose niacin, or
      gemfibrozil may produce myopathy with or without rhabdomyolysis. Interactions
      with other commonly prescribed agents, such as bile acid sequestrants, coumarin
      anticoagulants, and cardiovascular drugs, may alter the pharmacokinetics of
      either drug, but the clinical significance is generally minor. Food may affect
      plasma lovastatin concentrations, systemic pravastatin bioavailability, and the
      maximum serum concentration (Cmax) and time to achieve Cmax for fluvastatin.
      Hepatic dysfunction may influence the pharmacokinetics of pravastatin; all HMG
      CoA reductase inhibitors are contraindicated in patients with liver disease or
      unexplained elevations in serum aminotransferases. Severe renal insufficiency may
      necessitate dosage modification in lovastatin recipients. Renal dysfunction seems
      to affect the pharmacokinetics of pravastatin, simvastatin, and fluvastatin only
      minimally, but caution is still warranted. Although the HMG-CoA reductase
      inhibitors rarely have severe adverse effects, they may interact, in some cases
      dangerously, with other drugs, with food, and with disease states.

PMID- 7583828
TI  - Making a difference for patients, one pharmacist at a time.

PMID- 7583827
TI  - Fluctuations in syringe-pump infusions: association with blood pressure
      variations in infants.
AB  - Flow continuity of two brands of syringe pumps and four brands of syringes was
      studied as a possible cause of hemodynamic fluctuations observed in neonates.
      Cyclical fluctuations were observed in the blood pressure of 14 neonates
      receiving dopamine infusions by syringe pump at flow rates from 0.2 to 1 mL/hr.
      Atom 235 and IVAC 770 pumps and various sizes of Terumo, Becton Dickinson,
      Omnifix, and IVAC syringes were evaluated. Flow continuity was assessed by using
      a gravimetric technique. The force needed to initiate and maintain syringe
      plunger motion was also measured. Noncontinuous flow was encountered most
      commonly with Terumo syringes, which delivered boluses at regular intervals at
      flow rates up to 5 mL/hr. The interval was dependent on flow rate and was similar
      to the time between the blood pressure fluctuations observed clinically. The
      syringe plunger force exhibited regular fluctuations indicative of the plunger
      sticking, and simultaneous measurement of flow established a direct temporal
      relationship with boluses. The other syringes tested did not exhibit such
      fluctuations. No differences were found between the two syringe pumps. Syringe
      plunger sticking, resulting in intermittent boluses and potential blood pressure
      fluctuations, may occur at low flow rates and with certain syringe brands. This
      appeared to be the cause of hemodynamic fluctuations in neonates receiving
      dopamine infusions.

PMID- 7583829
TI  - An essential ingredient.

PMID- 7583830
TI  - Society shows strength in a changing climate.

PMID- 7583832
TI  - ASHP directory.

PMID- 7583831
TI  - Mastering the forces of change.

PMID- 7583833
TI  - Prescribing medications: changing the paradigm for a changing health care system.

PMID- 7583834
TI  - The key to pharmacist prescribing: collaboration.

PMID- 7583835
TI  - Do pharmacists need prescribing privileges to implement pharmaceutical care?

PMID- 7583837
TI  - Sibling rivalry?

PMID- 7583836
TI  - Correction to drug facts and comparisons.

PMID- 7583838
TI  - Bioavailability of itraconazole from oral liquids in question.

PMID- 7583839
TI  - Collaborative drug therapy management.

PMID- 7583840
TI  - Measurement of organic acids, aldehydes, and ketones in residential environments
      and their relation to ozone.
AB  - Ozone and several polar volatile organic compounds (VOCs) including organic acids
      and carbonyls (aldehydes and ketones) were measured over an approximately 24 hour
      period in four residences during the winter of 1993 and in nine residences during
      the summer of 1993. All residences were in the greater Boston, Massachusetts
      area. The relation of the polar VOCs to the ozone concentration was examined.
      Indoor carbonyl concentrations were similar between the summer and winter, with
      the total mean winter concentration being 31.7 ppb and the total mean summer
      concentration being 36.6 ppb. However, the average air exchange rate was 0.9 hr-1
      during the winter and 2.6 hr-1 during the summer. Therefore, the estimated
      carbonyl emission rates were significantly higher during the summer. Indoor
      organic acid concentrations were about twice as high during the summer as during
      the winter. For formic acid, the indoor winter mean was 9.8 ppb, and the summer
      indoor mean was 17.8 ppb. For acetic acid, the indoor winter mean was 15.5 ppb,
      and the summer indoor mean was 28.7 ppb. The concentrations of the polar VOCs
      were found to be significantly correlated with one another. Also, the emission
      rates of the polar VOCs were found to be correlated with both the environmental
      variables such as temperature and relative humidity and the ozone removal rate;
      however, it was difficult to apportion the relative effects of the environmental
      variables and the ozone removal.

PMID- 7583841
TI  - The use of health risk assessment to estimate desirable sampling detection
      limits.
AB  - The inclusion of non-detected chemicals in a health risk assessment may lead, in
      some cases, to estimated risks that exceed regulatory thresholds, because one
      must use the detection limit or half of the detection limit. This study presents
      a methodology which will allow one to estimate appropriate detection limits by
      conducting a health risk assessment prior to the source sampling program. The
      advantages and shortcomings of various levels of detail in the risk assessment to
      determine those detection limits are discussed. The application of the
      methodology is demonstrated with a case study of the potential health effects of
      power plant stack emissions.

PMID- 7583842
TI  - Olfaction and rhinitis.

PMID- 7583843
TI  - Allergenic cross-reactivity of foods and characterization of food allergens and
      extracts.
AB  - OBJECTIVE: The intent of this review article is to familiarize the reader with
      the clinical implications of cross-allergenicity among foods, the allergens
      involved in the oral allergy syndrome, and the progress to date in the
      identification of major food allergens. DATA SOURCES: English language papers
      identified through a Medline search and bibliographies of the identified papers.
      STUDY SELECTION: Reference were selected that provided historical background or
      contributed significantly to our current understanding of the objectives.
      RESULTS: (1) Cross-allergenicity in food families is commonly demonstrated in
      vitro or by skin testing, but oral challenge results indicate that clinically
      relevant food allergy is usually specific, and dietary restrictions of entire
      food families are rarely needed. (2) Patients with pollinosis and the oral
      allergy syndrome have IgE binding that cross-reacts secondarily to binding of
      highly homologous proteins found in various unrelated plants (pollens) and foods.
      (3) Identification and characterization of several major food allergens from
      codfish, milk, egg, peanut, soybean, and shrimp have been accomplished. (4)
      Commercial food allergy extracts are currently non-standardized and not well
      characterized. CONCLUSIONS: Accurate diagnosis of food allergy is essential
      because of the potential for serious adverse reactions, but this fact should not
      lead to the unnecessary prescription of overly restricted diets based solely on
      results of in vitro or skin testing. The further identification of major
      allergenic components of food and the identification of specific IgE antibodies
      to these allergens should make the clinical approach to the treatment,
      understanding, and diagnosis of food hypersensitivity easier.

PMID- 7583844
TI  - Noncardiogenic pulmonary edema due to radiocontrast media.

PMID- 7583845
TI  - Allergic rhinitis and olfactory loss.
AB  - BACKGROUND: Allergic rhinitis is associated with reports of olfactory loss, but
      there are few formal investigations. Patients with diminished smell function
      frequently have nasal polyps or sinusitis, making it difficult to separate the
      impact of allergic rhinitis from the effects of these other problems. OBJECTIVE:
      The goals of this descriptive study were to establish the prevalence of positive
      skin tests in patients reporting rhinitis and olfactory deficiency, and to assess
      olfactory function and the results of skin testing in a patient group with
      chronic rhinitis but without concomitant sinusitis or nasal polyps. METHODS:
      Sixty-two patients reporting olfactory loss and chronic rhinitis were examined by
      history, physical examination, olfactory testing, skin testing with perennial and
      seasonal allergens, endoscopic rhinoscopy, and CT scan of the paranasal sinuses.
      RESULTS: Seventy-one percent of all the subjects had at least one positive skin
      test, 69% to a perennial allergen, and 58% to mite. Eighty-two percent of the 28
      subjects with chronic rhinitis but no evidence of polyps or sinusitis had
      positive tests. The mean olfactory score for this rhinitis group was 4.35,
      consistent with moderate hyposmia. The mean olfactory score of 34 subjects with
      polyps and/or chronic sinusitis was 0.61, consistent with anosmia, and
      significantly lower (P < .001). Sixty-two percent of this group had positive skin
      tests. CONCLUSION: These subjects who experienced olfactory loss and rhinitis
      appeared to have a high prevalence of allergic rhinitis as suggested by the
      number of positive skin tests. Olfactory loss was observed in patients without
      polyps or sinusitis, which suggests that allergic processes may have affected
      olfactory function.

PMID- 7583846
TI  - Biologic potency and immunoblotting studies of extracts of three cockroach
      species.
AB  - BACKGROUND: Although cockroaches are responsible for severe allergic disease,
      cockroach extracts are not yet standardized by the ID50EAL method, nor have the
      allergens been completely characterized. OBJECTIVE: To determine biologic potency
      and immunoblotting patterns of whole-body extracts of three cockroach species:
      Periplaneta americana, Blattella germanica, and Blatta orientalis. METHOD: Twenty
      four subjects puncture test positive to mixed cockroach extract were puncture
      tested with the three extracts. Fourteen qualified for endpoint titration testing
      by the ID50EAL method to P. americana with a sum of erythema (sigma E) > or = 20
      mm by puncture testing, while 13 qualified for B. germanica and 12 qualified for
      B. orientalis. RESULTS: The mean D50s were 9.67 +/- 1.33 (mean +/- SD) for P.
      americana, 10.24 +/- 1.16 for B. germanica, and 10.36 +/- 1.40 for B. orientalis,
      resulting in a potency of 1000 BAU/mL for each extract. Omitting data from
      subjects with puncture sigma E < 30 mm did not change the calculated potency.
      Sixteen serum specimens revealed up to 17 bands with molecular weight 14 to 263
      kD by SDS-PAGE immunoblotting. Four specimens showed no bands; of these, one had
      a positive RAST only to P. americana and one only to B. germanica. There was no
      correlation between number of bands or RAST counts with D50. CONCLUSIONS: IgE
      immunoblots of cockroach-allergic patients vary considerably as to the number and
      intensity of bands. Most patients react similarly to all three species. Current
      nonstandardized products (1:10 wt/vol) in glycero-Coca's solution appear to
      contain approximately 1000 BAU/mL. Ideally these extracts should be more potent,
      eg, 10,000 BAU/mL.

PMID- 7583847
TI  - Major cat allergen (Fel d I) levels in the homes of patients with asthma and
      their relationship to sensitization to cat dander.
AB  - BACKGROUND: Exposure and sensitization to the major cat allergen, Felis
      domesticus allergen I (Fel d I), significant causes of allergic respiratory
      disease. Many patients who are allergic to cats, however, do not own a cat and
      there is not an obvious source of allergen in their home environment. OBJECTIVE:
      We investigated the levels of Fel d I in dust from homes of 120 subjects with
      asthma in two climatologically diverse Canadian cities (Vancouver and Winnipeg).
      Fel d I levels were related to exposure to cats as well as to skin reactivity to
      cat dander. METHODS: Dust samples from bedroom floors and mattresses were
      collected in four different seasons and Fel d I content was determined by 2-site
      monoclonal antibody based-ELISA. RESULTS: Although only 18 patients (15%) were
      cat owners, detectable levels of Fel d I were found on at least one occasion in
      all homes. The geometric mean concentration of Fel d I on floors was 1.15
      micrograms/g of dust (range 0.07 to 26.3 micrograms/g) and on mattresses 0.89
      micrograms/g (range 0.01 to 17.4 micrograms/g). Seasonal variation of Fel d I
      levels was only observed in Winnipeg, where Fel d I concentrations were highest
      in the winter and spring compared with either summer (P < .05) or autumn (P <
      .005). The highest Fel d I levels were found in homes with a cat (P < .05),
      however, rather high levels were also found in homes of patients who did not have
      a cat but visited others with cats. Cat dander was the most frequent sensitizer
      (60%) in these patients but no correlation was found between the size of the
      wheal induced by cat dander extract and Fel d I levels in dust samples.
      CONCLUSION: Cat allergen was universally found in homes of asthmatic patients and
      this may explain the high frequency of cat sensitization among patients with
      asthma in these two cities. A seasonal variation in cat allergen was observed in
      Winnipeg with no variation in Vancouver.

PMID- 7583849
TI  - Prevalence of house dust mites in the Rocky Mountain states.
AB  - BACKGROUND: Due to low rainfall and high elevation the ten Rocky Mountain states
      would not be expected to have the indoor humidity required to support the growth
      of significant numbers of house dust mites. Nevertheless, a recent survey
      reported that house dust mite allergen levels were not significantly different in
      the various regions of the United States, including the arid and mountainous
      regions. METHODS: Each summer for 5 years (1988-92) patients with bronchial
      asthma scheduled to be evaluated at the National Jewish Center for Immunology and
      Respiratory Medicine were invited to submit a dust sample from their mattress or
      bedroom carpet for mite analysis. RESULTS: Fifty-eight patients from the ten
      Rocky Mountain states submitted dust specimens. Forty-eight contained no mites,
      five had levels of mites considered clinically insignificant (less than 100
      mites/g dust), three contained 100 mites/g of dust, a level at the threshold of
      significance, and two had high levels of mites (1,000 and 3,000 mites/g). Both of
      the homes with high mite levels had specific sources of excess moisture. Twenty
      eight patients from adjacent states also submitted dust specimens. Significant
      levels of mites were encountered in specimens from these states reflecting the
      transition to zones of greater humidity and lower elevation. CONCLUSION: Except
      in homes with unusual sources of humidity, significant levels of house dust mites
      are rarely encountered in homes in the ten Rocky Mountain states.

PMID- 7583848
TI  - IgE levels in pediatric HIV-1 infection.
AB  - BACKGROUND: Atopic symptoms such as sinusitis, eczema, and wheezing are common in
      human immunodeficiency virus (HIV)-infected children. OBJECTIVE: To determine
      whether IgE levels are increased in HIV-seropositive children, and to determine
      whether there is a relationship between IgE, stage of disease, and atopic
      symptoms. METHODS: Levels of serum IgE and parameters of HIV infection, including
      absolute CD4 and CD8 T lymphocyte counts, and serum levels of neopterin, beta 2
      microglobulin and HIV P24 antigen were measured. Clinical parameters including
      stage of disease, opportunistic infections, and atopic symptoms were recorded.
      RESULTS: IgE was increased prior to 1 year of age and mean levels remained
      elevated through age 6 years but regressed to the normal mean in children ages 7
      to 9. There was a strong association between increased IgE and the presence of
      secondary disseminated or systemic diseases including pulmonary lymphoid
      hyperplasia, Pneumocystis carinii pneumonia, or disseminated cytomegalovirus
      infection. There was no correlation between CD4 levels and IgE levels (r = .03).
      The relationship between IgE and serum P24 antigen, beta 2 microglobulin, and
      neopterin levels was also analyzed. A weak positive correlation was found only
      with serum p24 antigen levels (r = .24). Atopic symptoms were found in a
      subpopulation of these children, with wheezing occurring in 27% of all patients,
      atopic dermatitis in 5%, drug reactions in 7% and sinusitis in 8% but IgE levels
      were not significantly elevated in patients with atopic symptoms. CONCLUSIONS:
      These findings demonstrate that serum IgE is increased in children very early
      after HIV infection and that IgE levels increase in association with HIV
      associated systemic disease. Increased IgE is not associated with atopic symptoms
      in children.

PMID- 7583850
TI  - Anaphylaxis to mustard as a masked allergen in "chicken dips".
AB  - BACKGROUND: Masked allergens in processed foods are sometimes responsible for
      "idiopathic" anaphylaxis because of the lack of full ingredient labeling.
      Patients, even if they are aware of a specific hypersensitivity, may be unaware
      of trace amounts of the offending allergen(s) that are present in these products.
      METHODS: We report a case of severe anaphylaxis to mustard masked in "chicken
      dips." A 38-year-old woman had an anaphylactic reaction beginning 20 minutes
      after eating "chicken dips" in a fast food restaurant. She was treated
      successfully in an emergency room and then referred to us for evaluation. We
      performed skin prick tests, IgE antibody, and inhibition assays to identify
      allergens in foods eaten just prior to the anaphylactic reaction. RESULTS: She
      had a history of allergy to mustard. Skin prick tests revealed sensitivity to
      mustard, coriander, and curry powder, which contains mustard. She had 56.3 KU/L
      mustard-specific serum IgE antibody in a Phadebas CAP RAST assay (Pharmacia,
      Sweden). The mustard RAST was inhibited with an extract of "chicken dips,"
      confirming the presence of mustard in "chicken dips." CONCLUSIONS: This case
      points out the risk of masked allergens in modern food products and the value of
      the RAST inhibition assay for the identification of such hidden allergens.

PMID- 7583851
TI  - Allergic bronchopulmonary aspergillosis presenting with cough variant asthma and
      identifiable source of Aspergillus fumigatus.
AB  - BACKGROUND: A 76-year-old man developed allergic bronchopulmonary aspergillosis
      initially presenting with cough variant asthma. Symptoms worsened after exposure
      to ground mulch which was an identifiable source of Aspergillus fumigatus.
      Symptoms improved after corticosteroids and avoidance measures were instituted.
      OBJECTIVE: To report a case of allergic bronchopulmonary aspergillosis presenting
      as cough variant asthma with identifiable source of Aspergillus fumigatus.
      METHODS: Single case report. Serum precipitating antibodies against Aspergillus
      fumigatus were tested using gel diffusion techniques. Total IgE, specific IgE,
      and IgG indices were measured by ELISA. Cutaneous reactivity to Aspergillus
      fumigatus was also tested. RESULTS: Skin test and serum precipitating antibodies
      to Aspergillus fumigatus were positive. Precipitins were also detected between
      Aspergillus fumigatus and the mulch. Total serum IgE was 538 IU/mL (1290 ng/mL)
      which declined to 228 IU/mL (544 ng/mL) after corticosteroid therapy. IgE index =
      1.10 and IgG index = 2.86. CONCLUSION: Allergic bronchopulmonary aspergillosis
      can present as cough variant asthma. Identification of exacerbating factors such
      as sources of Aspergillus fumigatus are important in management.

PMID- 7583852
TI  - Tannic acid's effect on bird antigen.
AB  - BACKGROUND: Birds have been associated with many diseases including
      hypersensitivity pneumonitis and allergic diseases such as asthma and rhinitis.
      Bird antigen from homes of patients with hypersensitivity pneumonitis persists
      long after the bird is removed from the home. This may account for the
      persistence of symptoms, signs, and bird-specific IgG in patients with
      hypersensitivity pneumonitis. Tannic acid application has been effective in
      decreasing cat and mite allergen levels. No data have been available on tannic
      acid's effect on bird antigen. OBJECTIVE: It is the purpose of this study to
      determine whether tannic acid reduces bird antigen in the home. METHOD: Dust
      samples were collected from homes with bird antigen before and after application
      of tannic acid. Samples were assayed for bird antigen levels using a competitive
      inhibition ELISA. Pre- and post-bird antigen levels were compared using a paired
      t test to determine whether antigen was reduced significantly. RESULTS: There was
      not a statistical difference between bird antigen levels before and after
      application of tannic acid as compared by paired t test (P = .09). CONCLUSION:
      Tannic acid is not effective in decreasing bird antigen levels. In patients with
      hypersensitivity pneumonitis or allergic disease to birds, the bird should be
      removed from the home and environmental cleanup should be undertaken, but tannic
      acid application is not indicated.

PMID- 7583854
TI  - Childhood asthma in Qatar.
AB  - BACKGROUND: Asthma is one of the most important causes of morbidity in childhood.
      Significant differences in the prevalence of asthma have been reported in
      children from different countries. OBJECTIVE: Our objective was to study the
      profile of asthmatic children in Qatar and compare it with other countries.
      METHODS: The study consisted of our outpatient asthmatic cases. It consists of
      detailed clinical questionnaires, physical examinations, and laboratory
      evaluations. RESULTS: Four hundred fourteen children with asthma were reviewed.
      The ages of the patients ranged from 7 months to 12 years with a mean of 6.15
      years. There were 135 girls (32.6%) and 279 boys (67.4%). Seventy percent of
      patients had their first episodes within the first 2 years of life. Viral
      respiratory infections were the most common precipitating factor (95.17%). Fumes
      were incriminated as a triggering factor in 36% of patients with Bokhour
      representing 54% of them. The majority of cases were moderate in severity
      (56.52%), while 27.78% were mild and 15.7% of cases were severe. Fifty percent of
      patients had been hospitalized at least once. Eighty-six percent had positive
      family histories of allergic diseases. Absolute eosinophil counts of more than
      500 cells/mm3 were found in 36.62%. Total serum IgE was elevated for age in
      61.59%. Positive skin tests to significant antigens were noted in 80.4% of cases.
      CONCLUSIONS: Our study describes the characteristic findings of asthma in Qatari
      children which are similar to reports from other developing countries except that
      our patients were younger in age of onset and Bokhour (an Arabian Gulf incense)
      was an important precipitating factor. It will help to improve understanding and
      management of asthma.

PMID- 7583853
TI  - English plantain and psyllium: lack of cross-allergenicity by crossed
      immunoelectrophoresis.
AB  - BACKGROUND: English plantain (Plantago lanceolata) weed pollen and psyllium
      (Plantago ovata) husk dust are inhalant allergens. Because of the phylogenetic
      relationship between these plant species, cross-allergenicity has been a concern.
      OBJECTIVE: The purpose of this study was to investigate the possible cross
      allergenicity of plantain and psyllium. METHODS: Homologous and heterologous
      crossed immunoelectrophoresis (CIE) were performed using a commercial English
      plantain pollen extract and an extract of psyllium seed embryo. Crossed
      radioimmunoelectrophoresis (CRIE) was performed using sera from subjects who were
      RAST positive only to plantain (group A), RAST positive only to psyllium (group
      B), RAST positive to both plantain and psyllium (group C), or RAST negative to
      both (group D). RESULTS: All of the group A plantain subjects showed IgE binding
      to at least one of the six plantain allergens in homologous plantain CRIEs while
      only one of the sera from the group B subjects reacted very weakly to these
      plantain allergens. In homologous psyllium CRIE, all group B subjects showed
      pronounced IgE binding to 2 to 7 of the seven psyllium allergens. Several of the
      plantain subjects demonstrated only very weak binding to psyllium allergens.
      Heterologous CRIEs demonstrated little relevant IgE binding. CONCLUSIONS: These
      results indicate that there is little cross-allergenicity between psyllium husk
      and English plantain pollen.

PMID- 7583855
TI  - Comparison of serum and plasma leukotriene B4 levels in normal and asthmatic
      subjects.
AB  - BACKGROUND: Leukotriene B4 (LTB4) serum and plasma concentrations were reported
      to be higher in some asthmatic patients than in normal subjects; however,
      reported LTB4 concentrations in normal subjects vary widely. One study suggested
      that blood clotting causes the increased LTB4 concentration. OBJECTIVE: To
      determine whether LTB4 concentration is increased in asthmatic patients, and
      whether it is affected by clotting. METHODS: We studied seven normal subjects and
      nine clinically stable asthmatic patients. Venous blood was drawn into test tubes
      without additives; containing heparin; or containing heparin and cyclo- and
      lipoxygenase inhibitors. Cells were separated after 30 minutes. Leukotriene B4
      was measured by radioimmunoassay following its extraction from serum or plasma.
      In three subjects, plasma was separated also at times 0 through 30 minutes.
      RESULTS: Serum and plasma concentrations of LTB4 in normal volunteers and
      asthmatic patients were similar, but the variance of LTB4 concentrations among
      the asthmatic patients was significantly higher than in the normal subjects.
      Leukotriene B4 concentrations, measured in plasma only, were significantly
      reduced in both asthmatic and nonasthmatic subjects in the presence of
      inhibitors. There was no significant difference in LTB4 concentrations between
      time 0 and 30 minutes, but there was considerable variability. CONCLUSIONS: We
      conclude that clotting is unlikely to affect serum LTB4 concentrations.
      Leukotriene B4 serum and plasma concentrations are not consistently increased in
      asthmatic patients; however, LTB4 is synthesized during and possibly after blood
      has been drawn. Proper handling of the specimens and probably the addition of
      cyclo-oxygenase and lipoxygenase inhibitors is of the utmost importance for
      accurate LTB4 determination.

PMID- 7583856
TI  - Bezalip-induced anaphylaxis.

PMID- 7583857
TI  - Latex-specific IgE in patients evaluated for allergy.

PMID- 7583858
TI  - Clinical immunotherapy studies needed.

PMID- 7583860
TI  - Diagnostic complexity in a patient with asthma, pulmonary infiltrates, and
      eosinophilia.

PMID- 7583859
TI  - Interferons: their role in clinical practice.
AB  - OBJECTIVE: To describe the current indications and side effects of Interferons in
      the treatment of human disease together with sufficient background information to
      understand the rationale for their use. DATA SOURCES: Literature searches on
      interferons extended back to the time of their discovery. Citations were limited
      to English and human aspects. Reference lists from recent reviews were also
      consulted. STUDY SELECTION: Reviews of fundamental mechanisms were selected
      together with studies of individual clinical trials and anecdotal experiences
      with human use of interferons. CONCLUSIONS: Interferons are accepted therapy for
      a number of conditions. Their range of therapeutic uses will undoubtedly increase
      as further knowledge is obtained.

PMID- 7583861
TI  - Successful replacement of allergen-specific immunotherapy by allergen-mixture
      therapy.
AB  - BACKGROUND: Some clinicians utilize allergen-specific immunotherapy (specific
      therapy), employing only the extracts of allergens that produce positive skin
      tests. Others use allergen-mixture immunotherapy (mixture therapy), employing
      premixed extracts containing both skin reactive and non-reactive (irrelevant)
      allergens. OBJECTIVE: The purpose of this study was to compare the efficacy of
      these two approaches and to identify sensitization to irrelevant allergens
      included in mixture therapy. METHOD: A total of 20 adults with allergic
      rhinitis/asthma who were switched from successful specific therapy (average
      duration of 6.1 years) to mixture therapy (2.0 years) were evaluated with symptom
      medication scores, skin test results, and local/systemic reactions at three time
      points: before specific therapy, before, and 2 years after mixture therapy.
      RESULTS: Symptom-medication scores for all patients improved at the end of
      specific therapy and remained improved during mixture therapy (12.3 versus 12.0
      with P = .75). The sums of positive skin tests at three points were not different
      (7.8 versus 8.3 versus 9.8 with P > .4 at all points). Reaction rates did not
      differ either. Skin sensitization to irrelevant allergens occurred in five
      patients during mixture therapy. These patients, however, also experienced
      spontaneous conversions from negative to positive reactions to the allergens not
      included in the therapy, indicating that sensitization may be partly due to a
      spontaneous increase in skin reactivity. CONCLUSION: These findings suggest that
      allergen-mixture immunotherapy is as efficacious as allergen-specific therapy and
      may be associated with skin sensitization in some patients. There was no evidence
      of increased adverse clinical reaction.

PMID- 7583863
TI  - Seasonal characteristics of ragweed pollen dispersal in the United States.
AB  - BACKGROUND: The most definitive reports concerning the seasonal characteristics
      of ragweed (Ambrosia spp) pollen dispersal in the United States date back 60
      years to work conducted with gravity slide samples. OBJECTIVE: Volumetric pollen
      data from 23 sampling sites were used to study the ragweed pollen season.
      METHODS: The date of first and final pollen capture and the date with maximum
      airborne pollen concentration (the "peak date") were used to compare the pollen
      seasons at locations ranging from approximately 30 degrees N to 45 degrees N
      latitude. RESULTS: Sixteen cities located north of 38 degrees N possessed similar
      peak dates (P = 1), generally achieving maximum airborne pollen concentration in
      late August or early September. Four cities located south of 38 degrees N
      experienced later peak dates, with the most southerly city reaching maximum
      pollen levels in mid-October. Three cities located in the Northwest did not
      recover ragweed pollen in air samples. CONCLUSION: This study confirms earlier
      reports and suggests what time of year source avoidance is most critical for
      ragweed sensitive individuals in various locations.

PMID- 7583862
TI  - Efficacy of once daily extended-release theophylline in decreasing the use of
      inhaled beta 2-agonists in stable, mild-to-moderate asthma patients.
AB  - BACKGROUND/OBJECTIVE: The purpose of this study was to determine whether the
      addition of extended-release theophylline to the daily treatment regimen of
      inhaled beta 2-agonist users would result in decreased use of beta 2-agonist
      while maintaining similar efficacy for treatment of asthma. METHODS: This was a
      single-blind, multicenter (six sites) study. Sixty-one patients with a history of
      mild-to-moderate asthma treated with inhaled beta 2-agonist were randomized to
      treatment with Theo-24 (anhydrous extended-release capsules) plus inhaled beta 2
      agonist or placebo plus beta 2-agonist. Patients kept daily symptom diaries,
      measured peak flow rates, recorded puffs of inhaled beta 2-agonist, and adverse
      events during a 4-week treatment period. RESULTS: Fifty-five patients were
      included in the efficacy analysis. The primary efficacy variable in this study
      was the mean number of puffs (adjusted for baseline differences) of beta 2
      agonist inhaled per day. In this study, the addition of theophylline to the daily
      regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total
      daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with
      placebo. The differences were significant at the P < .05 level. For patients in
      the theophylline group, the number of puffs decreased from an unadjusted mean of
      9.81 at baseline to an adjusted mean of 6.78 after 4 weeks of treatment compared
      with 9.91 at baseline and 8.17 for the placebo group. There were no unexpected or
      serious adverse events. CONCLUSIONS: In this study, the addition of once daily,
      extended-release theophylline to the daily regimen of inhaled beta 2-agonist for
      4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at
      weeks 3 and 4 of treatment compared with placebo, while maintaining acceptable
      asthma symptom scores.

PMID- 7583866
TI  - Comparison of three methods of using the DermaPIK with the standard prick method
      for epicutaneous skin testing.
AB  - BACKGROUND: The Greer DermaPIK is a plastic disposable device used for
      epicutaneous allergy skin testing. Various methods have been proposed for
      applying this device. The recommended methods are to use it as either a punch or
      scratch device. A third method- the prick, uses the device similarly to standard
      prick testing with the bifurcated needle. OBJECTIVE: To compare three methods of
      using the DermaPIK for epicutaneous skin testing with the bifurcated needle.
      METHODS: Twenty volunteers with a mean age of 30 years (range 6 to 45) were skin
      tested using saline and histamine. Each test was done in triplicate on the back.
      Discomfort for each technique was rated on a scale from 0 to 100. Wheal and
      erythema were measured at 15 minutes and a photograph was taken. RESULTS: The
      scratch method was rated highest in discomfort. The mean coefficient of variation
      for the punch method was 39.2% for erythema which was significantly higher than
      for the other methods (P < .0001). The scratch method had a mean wheal and
      erythema to saline of 3.85 +/- 1.3 and 6.23 +/- 2.2 that was significantly larger
      than the other methods (P < .001). There was no difference between the prick
      method and the bifurcated needle for discomfort or size of wheal/erythema to
      saline or histamine. CONCLUSIONS: The punch method is too imprecise and the
      scratch method produces considerable dermatographism. The prick method was
      comparable to the bifurcated needle in discomfort, sensitivity and precision.

PMID- 7583865
TI  - Inhalation challenge effects of perfume scent strips in patients with asthma.
AB  - BACKGROUND: Perfume- and cologne-scented advertisement strips are widely used.
      There are, however, very few data on the adverse effects of perfume inhalation in
      asthmatic subjects. OBJECTIVES: This study was undertaken to determine whether
      perfume inhalation from magazine scent strips could exacerbate asthma. METHODS:
      Twenty-nine asthmatic adults and 13 normal subjects were included in the study.
      Histories were obtained and physical examinations performed. Asthma severity was
      determined by clinical criteria of the National Heart, Lung, and Blood Institute
      (NHLBI). Skin prick tests with common inhalant allergens and with the perfume
      under investigation were also performed. Four bronchial inhalation challenges
      were performed on each subject using commercial perfume scented strips, filter
      paper impregnated with perfume identical to that of the commercial strips, 70%
      isopropyl alcohol, and normal saline, respectively. Symptoms and signs were
      recorded before and after challenges. Pulmonary function studies were performed
      before and at 10, 20, and 30 minutes after challenges. RESULTS: Inhalational
      challenges using perfume produced significant declines in FEV1 in asthmatic
      patients when compared with control subjects. No significant change in FEV1 was
      noted after saline (placebo) challenge in asthmatic patients. The percent decline
      in FEV1 was significantly greater after challenge in severely asthmatic patients
      as compared with those with mild asthma. Chest tightness and wheezing occurred in
      20.7% of asthmatic patients after perfume challenges. Asthmatic exacerbations
      after perfume challenge occurred in 36%, 17%, and 8% of patients with severe,
      moderate, and mild asthma, respectively. Patients with atopic asthma had greater
      decreases in FEV1 after perfume challenge when compared with patients with
      nonallergic asthma. CONCLUSIONS: Perfume-scented strips in magazines can cause
      exacerbations of symptoms and airway obstruction in asthmatic patients. Severe
      and atopic asthma increases risk of adverse respiratory reactions to perfumes.

PMID- 7583867
TI  - Characterization of latex and chestnut antigens by immunoblotting.
AB  - BACKGROUND: Cross-reactions between latex, chestnut, and other fruits have been
      demonstrated by RAST, although the results show some discrepancies. OBJECTIVE: To
      detect and characterize cross-reacting antigens in both extracts by
      immunoblotting. METHODS: Polyclonal rabbit antisera were raised against
      ammoniated latex and an aqueous chestnut extract. The antigenic extracts were
      studied by immunoblotting using a diffusion transfer method. Cross-reactivities
      were measured by immunoblotting inhibition. RESULTS: Both antisera detected a
      high number of antigenic proteins in both latex and chestnut extracts. Latex was
      a good self-inhibitor and inhibitor of chestnut with respect to both antisera.
      Chestnut was only a good inhibitor for the two antisera on the chestnut-blot as
      well as on the latex-blot when the anti-chestnut antiserum was employed. No
      inhibition was obtained on latex immunoblotting by chestnut using anti-latex
      antiserum. CONCLUSIONS: The results suggested that latex and chestnut contained
      common epitopes detected by antibodies raised by immunization with both antigens.
      The anti-latex antiserum, however, possessed antibodies that could not be
      inhibited by other allergens. This could explain why latex has been described as
      a good inhibitor of chestnut-RAST while no inhibition by chestnut was found on
      the latex-RAST in latex and chestnut allergic patients. Other common pollen
      extracts were also inhibitors of immunoblotting with the exception of the
      latex/anti-latex pair. This suggests that antibodies induced by immunization with
      latex or chestnut showed unexpected cross-reactions.

PMID- 7583864
TI  - Salmeterol xinafoate in children on high dose inhaled steroids.
AB  - BACKGROUND: Current UK and international guidelines on asthma management
      recommend that, in pediatric patients still symptomatic on treatment with high
      dose inhaled corticosteroids, consideration should be given to the introduction
      of regular twice daily long-acting beta 2-agonists. OBJECTIVE: The purpose of
      this study was to assess the efficacy and safety of inhaled salmeterol xinafoate
      50 micrograms bid via the Diskhaler when added to the existing treatment of
      children with moderate to severe asthma. METHODS: A 12-week multicenter, double
      blind, placebo-controlled, parallel group study was conducted at 78 hospital
      centers throughout the United Kingdom, involving 210 asthmatic children aged
      between 4 and 16 years of age. Morning peak expiratory flow (PEF), evening PEF,
      night-time and daytime symptoms and relief medication usage were recorded daily
      by the patient or parent over a 12-week treatment period. RESULTS: Compared with
      placebo, the addition of salmeterol xinafoate to existing high dose inhaled
      corticosteroid treatment significantly improved mean morning PEF expressed as
      percent predicted (PEF-PP) during the first 4 weeks of treatment (median increase
      6.5 percentage points P < .001). This effect persisted throughout the 12-week
      treatment period (P < .05). Both groups demonstrated an overall improvement in
      mean morning PEF-PP, 7.5 percentage points for salmeterol xinafoate and 4
      percentage points for placebo. The mean evening PEF-PP followed a similar
      although less pronounced trend which was significant only during the first 4
      weeks of treatment (P = .014). Daytime relief medication and recorded symptoms
      were reduced significantly in both groups. There was a greater improvement in the
      number of symptom-free days during the first 4 weeks (P < .01) and the last 4
      weeks (P < .05) of treatment for salmeterol xinafoate. The overall incidence and
      nature of minor adverse events was similar in both groups. CONCLUSIONS: This
      study demonstrates that the addition of salmeterol xinafoate to inhaled
      corticosteroid therapy in symptomatic asthmatic children significantly improves
      morning PEF-PP, and reduces their symptoms and use of relief medication.

PMID- 7583868
TI  - Oxatomide reduces inflammatory events induced by allergen-specific conjunctival
      challenge.
AB  - BACKGROUND: Allergen-specific conjunctival challenge is a safe and reproducible
      experimental model to evaluate effectiveness and possible mechanism(s) of action
      of drugs employed in the treatment of allergic diseases. OBJECTIVE: The
      protective effect of oxatomide on inflammatory changes that follow allergen
      specific conjunctival challenge was assessed in 20 patients with
      rhinoconjunctivitis due to Parietaria judaica in a double-blind study. METHODS:
      After a screening allergen-specific conjunctival challenge, patients were
      randomized into two treatment groups, each being given oxatomide (oral tablets)
      at 60 mg daily or matching placebo for seven days during off-pollen season.
      Clinical evaluation, cytologic assessment (number of inflammatory cells and ICAM
      1 expression on epithelial cells) were assessed at baseline, 30 minutes, 6 hours,
      and 24 hours after allergen-specific conjunctival challenge, before and after
      treatment. In addition, electrocardiograms were obtained before and after
      treatment. RESULTS: Early phase reaction clinical events as well as total numbers
      of inflammatory cells were significantly reduced by oxatomide compared with
      placebo. Late phase reaction clinical events as well as total numbers of
      inflammatory cells were significantly reduced by oxatomide compared with placebo.
      ICAM-1 expression was significantly reduced by oxatomide in early phase reactions
      and late phase reactions compared with placebo. No pathologic cardiac events were
      detected in any subject. CONCLUSIONS: Oxatomide has a protective effect on
      clinical and cellular early phase reactions and late phase reactions (including
      ICAM-1 expression on epithelium) induced by allergen-specific conjunctival
      challenge and is safe and well tolerated.

PMID- 7583870
TI  - Influence of sample preparation on cellular glutathione recovery from adherent
      cells in culture.
AB  - During the last decade, the unbound glutathione content of cultured adherent
      cells has become a very important biological marker for many pharmacological and
      toxicological in vitro studies with regard to the protective role of the
      tripeptide in its reduced form (GSH). However, the literature does not provide
      extensive information on the influence of sample preparation on cellular GSH and
      thiol analyses. Using the fibroblast-like V79 cell line as model, we undertook a
      comparative study of the efficiency of different procedures reported in the
      literature with respect to GSH recovery. Depending on the preanalytical step, up
      to 10-fold discrepancies could be observed in the recovery of intracellular GSH.
      Different parameters that must be controlled in order to maximize GSH recovery
      are discussed. The optimal strategy consisted in rapid perchloric acid
      deproteinization performed directly in the dish, which was extremely valuable for
      preparing GSH samples from adherent cells, and especially from cells expressing
      elevated gamma-glutamyl transferase activity.

PMID- 7583869
TI  - Extensive subcutaneous fibrosis in a patient treated with alum precipitated
      allergenic extract.
AB  - BACKGROUND: Alum-precipitated allergenic extract (Allpyral) used for
      immunotherapy has been associated with subcutaneous nodule formation at injection
      sites. OBJECTIVE: We describe a severe localized reaction at the site of Allpyral
      injections and evaluate possible mechanisms for this reaction. METHODS: Case
      report with cutaneous patch testing and CAT scan imaging. RESULTS: The patient
      developed extensive subcutaneous inflammation and fibrosis with overlying skin
      changes which appear to be permanent. CAT scan findings were corroborative and
      cutaneous patch testing to aluminium was positive. CONCLUSIONS: Alum-precipitated
      allergenic extract used for immunotherapy caused extensive subcutaneous fibrosis
      with overlying skin changes at the site of injections. The lesions are
      disfiguring and appear to be permanent. This may be due in part to a type IV
      hypersensitivity response to the aluminum component of Allpyral extract. A CAT
      scan was valuable in demonstrating structural changes associated with this
      lesion.

PMID- 7583871
TI  - Effects of concanavalin A on desensitization kinetics of GABA responses in
      Achatina fulica neurons.
AB  - The effects of the lectin concanavalin A (Con A), on the kinetics of
      desensitization of the responses of voltage clamped Achatina fulica LP5 neuron to
      microperfused acetylcholine (ACh) and GABA were compared. Both ACh and GABA
      elicited increases in chloride conductance which decayed biphasically during
      prolonged applications of these agonists; an initial rapid decay was followed by
      a later slow decay. Con A (5 micrograms/ml) accelerated both the fast and the
      slow decays of responses to ACh. Con A (5 micrograms/ml) also accelerated the
      fast decay of responses to GABA, but the slow decay was unaffected, even by 20
      micrograms/ml or more of the lectin. It is suggested that, at least in the case
      of GABA receptor, the fast and slow decays involve distinct desensitization
      kinetics. The effects of Con A on the desensitization of the ACh and GABA
      responses were reversed by D-mannose, a competitive and specific inhibitor of Con
      A binding to membrane sugar residues. These results provide further evidence that
      receptor desensitization can be influenced by perturbing the sugar moieties
      associated with the subunits comprising these signalling macromolecules. The
      carbohydrate residues may play an important role in regulating desensitization of
      transmitter receptors.

PMID- 7583872
TI  - The enzymatic removal of a surfactant coating from quartz and kaolin by P388D1
      cells.
AB  - The macrophage-like cell line, P388D1, was exposed to dipalmitoyl lecithin (DPL)
      coated respirable quartz and kaolin, and the disappearance of the DPL was
      monitored for up to 9 days. The coating was removed rapidly at first (about 50%
      in the first 3 days) and then more slowly over the remaining 6 days, until about
      30% remained on day 9. The rate of DPL digestion was independent of the type of
      dust and the amount of coated dust within the cell, indicating the existence of
      an extracellular phospholipase activity. This extracellular phospholipase
      activity was partially characterized. It was sensitive to temperatures above 56
      degrees C, the presence of EDTA, the action of the proteases trypsin and
      proteinase K, and pH, being active at pH 7 but not at pH 5. This is consistent
      with reports in the literature of the existence of an extralysosomal
      phospholipase which is active at pH 7 and dependent on the presence of divalent
      metal ions. There was a dust-dependent difference in the extracellular rate of
      DPL digestion from quartz and kaolin. The coating was removed more slowly from
      the kaolin than it was from quartz. The removal of the DPL coating seen in the
      presence of cells was presumably due to both an intracellular and an
      extracellular phospholipase.

PMID- 7583874
TI  - An in vitro study on the cytotoxicity of chlorhexidine digluconate to human
      gingival cells.
AB  - Chlorhexidine digluconate is the active ingredient in mouthrinses used to prevent
      dental plaque and gingivitis. The in vitro cytotoxicity of chlorhexidine was
      evaluated with the Smulow-Glickman (S-G) gingival epithelial cell line. The
      potency of chlorhexidine was dependent on the length of exposure and composition
      of the exposure medium. The midpoint cytotoxicity values for 1-, 24-, and 72-h
      exposures were 0.106, 0.011, and 0.0045 mmol/L, respectively. S-G cells exposed
      for 2 h to chlorhexidine and then maintained for 48 h in chlorhexidine-free
      medium were unable to recover from the initial insult. The adverse effects of
      chlorhexidine on the plasma membrane were suggested by the leakage of lactic acid
      dehydrogenase from chlorhexidine-treated S-G cells and by the increased
      permeability of chlorhexidine-treated liposomes to Ca2+. The toxicity of a 24-h
      exposure to chlorhexidine to the S-G cells was progressively lessened as the
      content of fetal bovine serum (FBS) in the exposure medium was increased from 2%
      to 8%. The potency of a 1-h exposure to chlorhexidine was reduced in medium
      amended with albumin, lecithin, and heat-killed Escherichia coli. These
      reductions in toxicity were presumably due to the binding of the cationic
      chlorhexidine to the negatively charged chemical moieties of the components of
      FBS and of albumin and lecithin and of sites on the surfaces of bacteria.
      Combinations of chlorhexidine and carbamide peroxide were additive in their
      cytotoxicities.

PMID- 7583876
TI  - Once more into the breach.

PMID- 7583875
TI  - Assessment of sulfur mustard interaction with basement membrane components.
AB  - Bis-2-chloroethyl sulfide (sulfur mustard, HD) is a bifunctional alkylating agent
      which causes severe vesication characterized by slow wound healing. Our previous
      studies have shown that the vesicant HD disrupts the epidermal-dermal junction at
      the lamina lucida of the basement membrane. The purpose of this study was to
      examine whether HD directly modifies basement membrane components (BMCs), and to
      evaluate the effect of HD on the cell adhesive activity of BMCs. EHS laminin was
      incubated with [14C]HD, and extracted by gel filtration. Analysis of the [14C]HD
      conjugated laminin fraction by a reduced sodium dodecyl sulfate-polyacrylaminde
      gel electrophoresis (SDS-PAGE) revealed the incorporation of radioactivity into
      both laminin subunits and a laminin trimer resistant to dissociation in reduced
      SDS-PAGE sample buffer, suggesting direct alkylation and cross-linking of EHS
      laminin by [14C]HD. Normal human foreskin epidermal keratinocytes were
      biosynthetically labeled with [35S]cysteine. 35S-labeled laminin isoforms,
      Ae.B1e.B2e. laminin and K.B1e.B2e. laminin (using the nomenclature of Engel),
      fibronectin, and heparan sulfate proteoglycan were isolated by
      immunoprecipitation from the cell culture medium, treated with HD or ethanol as
      control, and then analyzed by SDS-PAGE. On reduced SDS gels, these three BMCs not
      treated with HD showed the typical profile of dissociated subunits. However, HD
      treatment caused the appearance of higher molecular weight bands indicative of
      cross-linking of subunits within these BMCs. The HD scavengers sodium thiosulfate
      and cysteine prevented the cross-linking of BMC subunits by HD. Finally, tissue
      culture dishes coated with laminin or fibronectin were treated with HD or ethanol
      as a control, and human keratinocytes were plated on the BMC-coated surfaces.
      After 20 h of incubation, it was observed that cell adhesion was decreased
      significantly on the BMC-coated surfaces treated with HD. As expected, the
      preincubation of HD with cysteine diminished the HD inhibition of cell adhesion.
      Thus, HD alkylates adhesive macromolecules of the basement membrane zone and
      inhibits their cell adhesive activity. These findings support the hypothesis that
      the alkylation of basement membrane components by HD destabilizes the epidermal
      dermal junction in the process of HD-induced vesication. The failure of the HD
      alkylated BMCs to support the attachment of keratinocytes might also contribute
      to the slow reepithelialization of the wound site which is characteristic of HD
      induced blistering.

PMID- 7583873
TI  - Chronic and acute ethanol treatment modifies fluidity and composition in plasma
      membranes of a human hepatic cell line (WRL-68).
AB  - The aim of this study was to compare the effects of chronic (0.1 mol/L ethanol
      exposure during 30 days) and acute (0.5 mol/L ethanol exposure during 24 h)
      ethanol treatment on the physical properties and the lipid composition of plasma
      membranes of the WRL-68 cells (fetal human hepatic cell line). Using fluorescence
      polarization we found that ethanol treatment reduced membrane anisotropy due to
      disorganization of acyl chains in plasma membranes and consequently increased
      fluidity, as measured with the diphenylhexatriene probe. Addition of ethanol in
      vitro reduced anisotropy in control plasma membranes, whereas chronically ethanol
      treated plasma membranes were relatively tolerant to the in vitro addition of
      ethanol. Acutely ethanol-treated plasma membranes exhibited a smaller anisotropy
      parameter value than control plasma membranes. We found a decrease in total
      phospholipid content in acute ethanol WRL-68 plasma membranes. Cholesterol
      content was increased in both ethanol treatments, and we also found a significant
      decrease in phosphatidylinositol and phosphatidylcholine and an increase in
      phosphatidylethanolamine content in ethanol-treated plasma membranes. Our data
      showed that ethanol treatment decreased the anisotropy parameter consistently
      with increased fluidity, while increasing the cholesterol/phospholipid ratio of
      plasma membranes of WRL-68 cells, but only chronically ethanol-treated plasma
      membranes exhibited tolerance to the in vitro addition of ethanol. It is
      important to note that some changes that were interpreted as a result of chronic
      ethanol treatment were also present in short-period ethanol treatments.

PMID- 7583877
TI  - Advanced practice nursing is the answer ... what is the question?

PMID- 7583878
TI  - Revisiting interdisciplinary education: one way to build an ark.

PMID- 7583880
TI  - Family practice health care: making collaborative practice a reality.

PMID- 7583883
TI  - Paul Wellstone is not standing aside. Interview by Andrea Steiner.

PMID- 7583882
TI  - Re-examining Nightingale's vision: clinical excellence and health services policy
      and research.

PMID- 7583879
TI  - Advanced practice education for the twenty-first century.

PMID- 7583884
TI  - Diploma programs in nursing accredited by the National League for Nursing 1995
      1996.

PMID- 7583881
TI  - Seamless progression: a competency-based program for nursing education.

PMID- 7583885
TI  - Practical nursing programs accredited by the National League for Nursing 1995
      1996.

PMID- 7583886
TI  - [Development of locoregional anesthesia and management of postoperative pain:
      inadequate!].

PMID- 7583887
TI  - [Does neuroplasticity have a role on postoperative pain?].
AB  - The neurophysiologic concept of neuroplasticity represents one of the current
      basis of the pathophysiology of painful post-injury phenomenons (postoperative,
      post-traumatic...). Deriving directly from these experimental data, the idea of
      preemptive analgesia has gradually developed in the last five years, the central
      question being to know if an analgesic intervention preceding surgical
      intervention is more efficient, as efficient, or less efficient than the same
      intervention following surgery. The authors bring current data of the literature
      in favor of the role of neuroplasticity in the genesis and the persistence of
      painful states in the course of postoperative outcome. A review of the various
      clinical studies and controversies published is proposed, in the attempt to make
      the point on current therapeutic implications of the concept of preemptive
      analgesia.

PMID- 7583888
TI  - [Optimal use of non opioid analgesics].
AB  - This review describes the mechanisms of analgesic effect, advantages and risks
      related to the perioperative use of non steroidal antiinflammatory drugs
      (NSAID's). The NSAID's should be used as the first analgesic, around the clock,
      with a rapid onset of the therapy. Their combination with other NSAID's
      (acetaminophen) or opioids can have an additive analgesic effect and may limit
      frequent secondary effects as nausea and vomiting. Their potential toxicity must
      be remembered and the contra indications, maximum doses and duration of treatment
      have to be respected.

PMID- 7583889
TI  - [Optimal use of the administration of morphine derivatives].
AB  - During the postoperative period, the efficacy of opioid treatment is different
      among patients. Indeed, an extreme variability exists between patients,
      concerning their analgesic requirement and their sensibility to opioids. To
      improve opioid analgesia, some empiric considerations must be observed: 1)
      Techniques of opioid administration must allow to titrate analgesic requirement.
      Patient Controlled Analgesia represents a real improvement and should be
      developed. 2) Occurrence of side effects must be avoided. The combination of
      different analgesics must be prescribed systematically, if there is no
      contraindication. 3) Opoid side effects must be appropriately treated, in order
      to improve the quality of analgesia. These simple measures require regular
      evaluation of opioid analgesia, and treatment of the side effects.

PMID- 7583890
TI  - [Optimal use of peripheral nerve blocks].
AB  - The advantages of regional over general anaesthesia have led to an increased use
      of peripheral nerve blocks. Among the few risks of regional anaesthesia are those
      of overdosage, systemic and neural toxicity. Techniques have been proposed to
      improve the success of peripheral nerve blocks and to avoid nerve damage or
      systemic toxicity. Nerve stimulator, anatomic landmarks, needles and anaesthetic
      solutions are discussed.

PMID- 7583891
TI  - [New routes for infiltration: intraperitoneal injections].
AB  - Intraperitoneal administration of local anaesthetics is frequently used during
      gynaecological laparoscopy and especially after laparoscopic sterilization where
      the solution may be instilled, sprayed or infiltrated around the clip or the
      rings. In addition, the subdiaphragmatic instillation of local anaesthetics by
      the surgeon during laparoscopy is followed by a decrease in the intensity of
      postoperative scapular pain which is known to last 2-3 days and is due to some
      degree of residual pneumoperitoneum. After laparoscopic cholecystectomy, the
      analgesic effects of the administration of local anaesthetics via the
      intraperitoneal route remain controversial. The pharmacokinetic data available
      which confirm the safety of doses up to 100 mg of bupivacaine or 800 mg of
      lidocaine, should encourage the use of larger doses, especially after
      cholecystectomy.

PMID- 7583892
TI  - [New routes for infiltration: surgical wound infiltration].
AB  - Wound infiltration with a local anaesthetic may be used either to provide
      anaesthesia for superficial surgery or for postoperative pain relief. In the
      latter situation, its efficacy is real but remains moderate and usually requires
      a combination with other analgesics. Ilio-iguinal and ilio-hypogastric block has
      been shown to have an analgesic efficacy close to that obtained with a wound
      infiltration but the duration of analgesia may be longer. These blocks remain
      unfrequently used in adults.

PMID- 7583893
TI  - [Spinal anesthesia in children].

PMID- 7583894
TI  - [Caudal anesthesia in children].
AB  - Caudal block is the most frequently epidural block performed in children. A
      better knowledge of the child anatomy, physiology and pharmacokinetics has
      increased the safety of regional anaesthesia in children. The technique of
      puncture has been adapted to the child anatomy and special needles fit for
      children are now manufactured. The children, as well as adult, have benefited of
      new drugs (opioids, alpha 2 agonists) which increase the indications regarding
      time duration or pain intensity. If complications are still possible the respect
      of safety rules and the use of adapted equipment make caudal block a safe
      regional anaesthesia.

PMID- 7583895
TI  - [Lumbar and sacral epidural anesthesia in children].
AB  - This article will briefly review the techniques of epidural anaesthesia via
      lumbar and sacral routes, as well as the indications and contraindications of the
      techniques. Guidelines for per- and postoperative use of epidural anaesthesia are
      provided.

PMID- 7583896
TI  - [Peripheral nerve block of the limbs in children].

PMID- 7583897
TI  - [Penile block. Block of ilio-inguinal and iliohypogastric nerves in children.
      Techniques, indications, advantages and adverse effects].
AB  - Peripheral blocks as penile blocks, ilio-inguinal ou ilio-hypogastric nerve
      blocks provide an useful alternative to caudal block in children, especially for
      penile surgery, herniotomy, and orchidopexy, frequently performed at this age. A
      precise anatomic location and a strict technique increase the success rate of
      these blocks. Complications are rare. Postoperative analgesia in ambulatory
      surgery is one of the best reasons to select these techniques. In addition they
      avoid prolonged motor effects observed with epidural anaesthesia.

PMID- 7583898
TI  - [Postoperative analgesia in children: techniques].

PMID- 7583899
TI  - [Hemodynamic effect of intrathecal clonidine].
AB  - Intrathecal administration of bupivacaine and clonidine results in a significant
      prolongation of both motor and sensitive blocks but side effects-hypotension and
      bradycardia-are observed. We compared two groups of patients allocated randomly.
      One group received intrathecal bupivacaine-morphine and the other one received
      clonidine-bupivacaine-morphine. In the group which received clonidine a blood
      pressure decrease was observed from 2nd to 8th hour, independently from the
      sympathetic block and easily corrected by i.v. ephedrine. Some possible
      explanations are discussed. No complications due to clonidine were observed.

PMID- 7583900
TI  - [Analgesia with intra-articular injection of buprenorphine after surgery of the
      shoulder].
AB  - The effect of 10 ml of intra-articular buprenorphine (0.30 mg) or normal saline
      on postoperative pain after shoulder surgery was studied in a randomized,
      prospective, double-blind study in 30 ASA I-II patients receiving general
      anaesthesia. The pain scores (Five Point Scale ranging from "no pain" to
      "unbearable pain" and Visual Analog Pain Scale) 1, 2, 3, 4, 6 and 24 hours after
      surgery, time to first analgesic use and total 6-hours and 24-hours analgesic
      requirements were recorded. VAPS was significantly lower in the buprenorphine
      group compared with placebo-treated patients one hour after surgery (p < 0.05).
      The time to first analgesic use was longer and total 6-h opioid requirements were
      lower in the buprenorphine group when compared with the control group (p < 0.05).
      No significant differences were detected in total 24-h analgesic requirements
      between the two groups. These results indicate that intra-articular injection of
      buprenorphine after shoulder surgery provides short analgesia. This effect may be
      mediated by systemic absorption.

PMID- 7583901
TI  - [Postoperative analgesia after ligamentoplasty of the knee. Comparison of
      epidural morphine and intravenous nalbuphine].
AB  - Surgery of the anterior cruciate ligament causes severe postoperative pain. This
      study aimed to compare efficacy and side effects of two postoperative analgesia
      methods, during 24 hours. Twenty healthy patients were assigned to two groups (n
      = 10): the patients of the first group were given by an epidural catheter 3 mg of
      morphine hydrochloride, every twelve hours. The patients of the second group
      received 2 mg h-1 of intravenous nalbuphine. The degree of pain was studied with
      a visual analogue scale. After the third postoperative hour, it was significantly
      higher in the second group, but the nalbuphine dose was low. The incidence of
      respiratory depression, nausea, pruritus was not statistically different between
      the groups, but 7/10 patients in the first group suffered of urinary retention
      (the first micturition was obtained 10.5 hours after the end of surgery in the
      first group and 5.3 h in the second one). Two patients needed an uretral
      catheter. These results might tend to show a greater efficactly of epidural
      morphine, with a higher incidence of urinary side effects.

PMID- 7583905
TI  - Early diagnosis and treatment of head and neck cancer.

PMID- 7583904
TI  - [Physiology of pain in the XVIII century].

PMID- 7583903
TI  - [Hyponatremia disclosing abdominal cystic lymphangioma].

PMID- 7583902
TI  - [Fatal hepatic necrosis during treatment with sodium valproate].
AB  - The authors report a case of fatal hepatic failure in a 19-year old young man
      suffering from absence seizures and treated for two months with valproic acid
      (VPA). The duration of VPA therapy before onset of clinical manifestations was
      four weeks. The prodromal symptoms were weakness, anorexia, and vomiting, then in
      a few weeks occurred a jaundice and an hepatic encephalopathy leading to death.
      Among laboratory findings disturbance of liver tests and particularly depressed
      levels of clotting factors were observed. The histologic study of the liver
      showed an extended centrolobular necrosis associated with fatty change and
      fibrosis. The mechanism of this hepatic failure remains unknown. The seriousness
      of this complication necessitates to respect any contraindications.

PMID- 7583907
TI  - Treatment of cancer of the head and neck.

PMID- 7583906
TI  - Early diagnosis of asymptomatic oral and oropharyngeal squamous cancers.
AB  - An examination of the oral cavity and oropharynx in asymptomatic patients at high
      risk requires an orderly visual inspection of the entire oral and oropharyngeal
      mucosa with particular attention to the tongue, floor of mouth, soft palate,
      uvula, tonsillar pillars, and the lingual aspects of the retromolar trigones.
      Completion and clear documentation of the entire examination should be recorded.
      Detected lesions that do not resolve in a reasonable length of time--two to three
      weeks--require intense and assiduous investigation. The following specifics
      should be considered. 1. Alcohol drinkers and cigarette smokers, especially those
      40 years of age and older, are at very high risk for the development of upper
      aerodigestive tract and lung squamous carcinomas. 2. The floor of the mouth, the
      ventrolateral tongue, and the soft palate complex are the high-risk sites within
      the oral cavity and oropharynx. 3. Persistent mucosal erythroplasia rather than
      leukoplakia is the earliest visual sign of oral and oropharyngeal carcinoma.
      These lesions should not be regarded merely as precancerous changes. The evidence
      indicates that these lesions in high-risk sites should be considered to be
      invasive carcinoma or carcinoma in situ unless proven otherwise by biopsy. 4.
      Toluidine blue staining is a useful diagnostic adjunct, particularly as a method
      of ruling out false-negative clinical impressions. It may also be used as a rinse
      in high-risk patients to encompass the entire oral mucosa after a negative
      clinical examination and as a guide to improve biopsy yields. 5. If oral or
      oropharyngeal cancer is identified, evaluations of the larynx, hypopharynx,
      esophagus, and lungs should be performed to rule out multiple primary
      cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7583910
TI  - Ovarian cancer.

PMID- 7583909
TI  - Breast cancer.

PMID- 7583908
TI  - The role of the primary care physician in tobacco use prevention and cessation.

PMID- 7583912
TI  - Oral fluid as a specimen for detection and confirmation of antibodies to human
      immunodeficiency virus type 1.
AB  - Paired serum and oral fluid specimens (n = 287) were collected with the Omni-Sal
      device and were assayed for the presence of antibodies to human immunodeficiency
      virus type 1 (HIV-1). Enzyme immunoassays (EIAs)--Abbott 3A11, an Organon Teknika
      Corporation research-use-only test, and the Murex GACELISA--were used per the
      manufacturers' inserts or were modified slightly to accommodate the oral fluid
      specimens. Compared with serum Western blot (immunoblot) results, each EIA had a
      sensitivity of 100% and the specificities were 89.6% for the Abbott 3A11 EIA,
      96.5% for the GACELISA, and 97.8% for the Organon Teknika Corporation EIA.
      Specificities based on specimens that were repeatedly reactive were 99.3% for all
      EIAs. A miniaturized Western blot technique used for confirmatory testing of both
      the serum and oral fluid specimens found 149 of the 287 samples to be HIV-1
      antibody positive in both sample types. The Western blot banding patterns
      observed for the serum and oral fluid specimens were essentially identical.
      Immunoglobulin G concentrations were determined for all oral fluid specimens and
      ranged from < 0.5 to > 40.0 micrograms/ml. Immunoglobulin G concentrations did
      not correlate with the ability of any of the EIAs to detect HIV-1-specific
      antibody or with the ability of the modified Western blot to detect HIV-1 protein
      specific antibodies.

PMID- 7583911
TI  - Structural and functional properties of human lambda-light-chain variable-region
      subgroups.

PMID- 7583914
TI  - Decreased T-cell proliferative response to common environmental antigens could be
      an indicator of early human immunodeficiency virus-mediated lymphocyte lesions.
AB  - To evaluate CD4+/CD29+ cells and their responses to different antigens in polar
      stages of human immunodeficiency virus (HIV) infection, we studied 26 HIV
      seropositive carriers (SPCs) and 15 patients with AIDS simultaneously with 20
      healthy volunteers (HVs) and 10 seronegative homosexual and bisexual men (SNH).
      CD3, CD4, CD29, and CD45RA phenotypes were analyzed by two-color flow cytometry.
      Significant depletion of CD4+ T cells and both memory (CD4+/CD29+) and naive
      (CD4+/CD45RA+) T-cell subsets was found among SPCs and AIDS patients compared
      with the numbers of such cells in the HV and SNH groups. Responses to optimal
      doses of Candida albicans, streptokinase, and tetanus toxoid were explored in
      peripheral blood mononuclear cells and CD4(+)- and CD4+/CD29(+)-enriched cell
      populations. In SPCs, the response to C. albicans in peripheral blood mononuclear
      cells showed a statistically significant diminution compared with the response of
      HVs (15,308 versus 35,951 cpm). In addition, a significantly reduced response to
      streptokinase was evident only when cell preparations were CD4+/CD29+ enriched
      (3,048 versus 10,367 cpm). Furthermore, the SPC group comprised seven responders
      to at least one antigen and seven nonresponders to any of the selected specific
      antigens. Absence of a response in these latter patients was independent of the
      absolute counts of memory and naive T-cell populations. The response to tetanus
      toxoid, although diminished in SPCs, was not significantly different from that in
      controls. Our results suggest that defective responses to common environmental
      antigens, unrelated to the absolute number of CD4+/CD29+ cells, is probably an
      early indicator of an HIV-induced lymphocyte lesion.

PMID- 7583913
TI  - Presence of neutralizing antibodies to heterologous human immunodeficiency virus
      type 1 isolates in sera of infected individuals is not predictive of rate of
      disease progression.
AB  - These studies were undertaken to examine whether the presence of human
      immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies in sera of infected
      individuals would alter the rate of disease progression. HIV-1-infected
      individuals (n = 87) were initially examined for neutralizing activity in vitro
      against both laboratory and tissue culture-adapted clinical heterologous HIV-1
      isolates. The neutralizing activities of sera were determined by a 90% or greater
      reduction in HIV-1 p24 levels in vitro. In a cross-sectional analysis of all
      infected individuals, we observed that sera from asymptomatic individuals
      neutralized a significantly greater number of heterologous HIV-1 isolates than
      sera from symptomatic patients. Patients who could be followed up longitudinally
      (n = 24) were then studied to determine the impact of neutralizing antibodies on
      the rate of disease progression. We observed no significant difference between
      the numbers of HIV-1 isolates neutralized in vitro by sera from patients who
      remained clinically stable and by those from patients who progressed rapidly. Our
      data indicated that the presence or absence of neutralizing antibodies to
      heterologous HIV-1 isolates was not associated with the rate of disease
      progression.

PMID- 7583915
TI  - Reversal of immunosuppression of lymphocyte proliferation caused by sera from
      persons with AIDS.
AB  - Sera from persons with AIDS contain inhibitors of lymphocyte proliferation.
      Inhibitory activity can be detected before the development of AIDS in humans.
      There appear to be at least three distinct suppressive moieties, one of which is
      prostaglandin E2. We and others had previously shown that serum samples from
      subjects with AIDS contained antibody to the cell line HUT 102B2. We attempted to
      remove this antibody and to determine if that action would also remove the
      inhibitory activity present in human immunodeficiency virus-positive sera. We
      incubated sera from subjects with AIDS with HUT 102B2 cells and tested the
      resultant supernatants for inhibition of cell proliferation. We found that this
      procedure significantly reversed inhibition by serum. Other cells and cell lines
      were similarly tested, but only HUT 102B2 cells absorbed the inhibitory
      product(s). However, we determined that secretory material from another cell
      line, MLA 144, also reversed inhibition. The physical characteristics of the
      supernatant were investigated. Thus, two procedures and likely separate products,
      possibly cytokines, reverse immunosuppression by sera from persons with AIDS.

PMID- 7583916
TI  - Intrinsic defect in B cells of patients with hyper-immunoglobulin M syndrome.
AB  - We challenge the theory that the CD40-CD40 ligand is the only explanation for X
      linked immunodeficiency in patients with hyper-immunoglobulin M (IgM) syndrome
      (HIGM1), and we demonstrate an intrinsic defect in the patients' B cells.
      Patients with HIGM1 have a defective CD40 ligand on their activated T-helper
      cells; therefore, they cannot receive signals for isotype switching when the
      cells are activated by T cell-dependent antigens. We activated mononuclear cells
      from three patients with HIGM1 and from three healthy blood donors with T cell
      independent mitogens and studied their proliferative responses and Ig secretion.
      Normal murine plasma membrane fragments were implanted into peripheral blood
      mononuclear cells, and the cells were activated with Staphylococcus aureus Cowan
      I, pokeweed mitogen, and lipopolysaccharide. This implantation significantly
      augmented the proliferative responses to the mitogens in two patients. However,
      it augmented IGM secretion in response to B-cell mitogens in only one patient. No
      IgG or IgA response could be detected in the implanted mononuclear cells that
      originated from patients with HIGM1, unlike implanted mononuclear cells from
      healthy donors, which responded by IgM, IgG, and IgA antibody secretion following
      their stimulation with B-cell mitogens. The data suggest that the B cells of
      patients with HIGM1 possess an additional defect which prevents Ig isotype
      switching in response to T cell-independent mitogens. This defect is not located
      in the membrane receptors or within the membrane enzymes.

PMID- 7583917
TI  - Use of hydroethidine and flow cytometry to assess the effects of leukocytes on
      the malarial parasite Plasmodium falciparum.
AB  - Flow cytometry was evaluated as a method of assessing in vitro the effects of
      leukocytes on blood-stage Plasmodium falciparum. Hydroethidine is converted by
      metabolizing cells to ethidium, a nucleic acid fluorochrome. After incubation
      with hydroethidine, viable and dead leukocytes and parasitized and uninfected
      erthrocytes could all be identified on the basis of fluorescence intensity and
      size. Leukocytes can therefore be eliminated from further analysis; this allows
      assessment, at any parasite developmental stage, of the level of parasitemia
      within erythrocytes in the presence of any of several types of leukocytes.
      Whether leukocytes actually kill intraerythrocytic parasites can therefore be
      determined and the level of cytotoxicity can be assessed. The ability of
      leukocytes to prevent merozoites from invading new erythrocytes, i.e., inhibition
      of parasite invasion, can also be assessed by this method. When erythrocytes
      containing schizont-stage parasites were cocultured with different leukocyte
      populations and the level of parasitemia was determined after merozoite release
      and invasion, only cultures containing gamma delta T cells inhibited parasite
      invasion. The different blood-stage forms of the parasite vary in nucleic acid
      content, which allows each of the developmental stages to be distinguished by
      flow cytometry; this permits assessment of changes in parasite development in the
      presence of leukocytes. Monocyte-derived macrophages (MDMs) appeared to have an
      effect on parasite development. In this instance, when erythrocytes containing
      ring-form parasites were cocultured with MDMs and harvested 24 h later, the
      parasites in cultures containing MDMs were at the late schizont stage, whereas
      parasites in control cultures were early trophozoites; this finding suggests that
      MDMs accelerate parasite development. Together, these results indicate that flow
      cytometry is potentially useful for measuring the following effects mediated by
      leukocytes: (i) level of cytotoxicity, (ii) changes in parasite development, and
      (iii) inhibition of parasite invasion.

PMID- 7583918
TI  - Impairment of monocytic function after influenza virus infection.
AB  - In order to analyze the immunosuppression associated with influenza virus
      infection, we investigated monocytic function in macrophage hybridoma cell lines
      5 weeks after infection with two strains of influenza virus. Clones 30 and 63,
      chosen for stability in long-term culture, were infected with two strains of
      influenza virus, X-31 and PR-8. Uniform infection of both cell lines was
      confirmed by intracytoplasmic staining with the antihemagglutinin strain-specific
      monoclonal antibodies PY 102 and PY 206. One week after infection, clones 30 and
      63 lost their ability to stimulate tetanus toxoid-specific major
      histocompatibility complex (MHC)-matched responder T cells. Coincident with the
      inability to stimulate MHC-matched T cells, there was diminished surface
      expression of class II MHC antigens and LFA-1-alpha and LFA-3 compared with that
      in uninfected cells: DR, 2.5 versus 10.6% (mean channel 0.3 versus 1.5); DQ, 1.6
      versus 15.6% (mean channel 0.3 versus 3.0); DP, 5.0 versus 30.9% (mean channel
      0.3 versus 2.0). LFA-1-alpha expression was reduced (13.1 versus 20.0%; mean
      channel 1.5 versus 2.0) while LFA-3 expression remained the same (22.2 versus
      324%; mean channel 3.0 versus 3.3). Class I MHC surface antigen expression was
      unaltered. Cytokine secretion was also perturbed, as interleukin 1-alpha (IL-1
      alpha) and IL-1-beta production was lost 1 week after infection. Production of IL
      12 and IL-10 was unchanged, while IL-6 production was increased. The viability of
      the T cells cocultured with 63Flu was unaltered, demonstrating that the inability
      of the MHC-restricted T cells to proliferate in response to tetanus toxoid was
      not due to a toxic effect of 63Flu. Interestingly, other accessory functions,
      including the ability to support mitogen- and anti-CD3-mediated T-cell
      proliferation, remained intact. These data suggest that alteration of macrophage
      function relating to viral infection occurs at multiple levels and may contribute
      to the immunosuppression observed following influenza virus infection.

PMID- 7583919
TI  - Differential effects of human immunodeficiency virus type 1 envelope protein
      gp120 on interferon production by mononuclear cells from adults and neonates.
AB  - While considerable progress in examining the course of human immunodeficiency
      virus (HIV) infection in adults has been made, a better understanding of the
      natural history of perinatal HIV infection remains to be obtained. Dysregulation
      of the production and functions of various cytokines, especially the interferons
      (IFNs), during HIV infections has been reported. Using an in vitro model system,
      we examined the effects of the HIV type 1 envelope protein, gp120 (10, 50, and
      100 ng/ml), on gamma IFN (IFN-gamma) and IFN-alpha production by lymphocytes from
      neonates and adults and also examined the potential regulatory effects of gp120
      on phorbol 12-myristate acetate (PMA)- and Sendai virus-induced IFN-gamma and IFN
      alpha production by lymphocytes. PMA at a concentration of 50 ng/ml plus 50 ng of
      calcium ionophore A23187 per ml was used to induce IFN-gamma, while 150
      hemagglutinating units of Sendai virus was used to induce IFN-alpha production.
      The antiviral activity of both IFN-alpha and IFN-gamma in leukocyte culture
      supernatants was assayed on BG-9 cells by a dye uptake technique using vesicular
      stomatitis virus as a challenge virus. Placental cord blood leukocyte (CBL)
      samples from healthy, term infants and adult peripheral blood leukocytes (APBL)
      produced no IFN in response to gp120. However, CBL produced significantly
      decreased levels of IFN-gamma compared with APBL in response to PMA plus
      ionophore. gp120 significantly suppressed both Sendai virus-induced IFN-alpha and
      PMA-induced IFN-gamma production by both CBL and APBL in a dose-dependent manner.
      However, gp120-induced suppression of IFN-alpha and IFN-gamma was significantly
      greater with CBL than with APBL. Treatment of CBL and APBL with gp120 did not
      induce any phenotypic alteration of the CD45 RO+ subset. Increased suppression of
      IFN-alpha and IFN-gamma production by gp120 in neonates may partially explain
      their apparent increased susceptibility to the clinical progression of HIV
      infections compared with that of adults.

PMID- 7583920
TI  - Development of monoclonal antibodies against Hantaan virus nucleocapsid protein.
AB  - Forty-five hybridoma cell lines producing monoclonal antibodies against Hantaan
      virus, the etiologic agent of hemorrhagic fever with renal syndrome, were
      generated by fusion of P3-X63-Ag8.V653 myeloma cells with spleen cells of mice
      immunized with inactivated Hantaan virus vaccine. Among these, 38 antibodies were
      identified as binding to the 48-kDa nucleocapsid protein by immunoblot assay or
      radioimmunoprecipitation. Twenty-six of them were of the immunoglobulin G1
      (IgG1), nine were of the IgG2a, and three were of the IgA isotype. According to
      cross-reactivities with other serotypes of the genus Hantavirus, the antibodies
      were classified into three groups: 6 antibodies specific to the Hantaan serotype
      (group I), 20 antibodies cross-reacting with Hantaan and Seoul serotypes (SR-11,
      Tchoupitoulas, and R22) (group II), and 12 antibodies cross-reacting with
      Hantaan, Seoul, and Prospect Hill serotypes (group III). None of the antibodies
      cross-reacted with the Puumala serotype. With a panel of antibodies of different
      cross-reactivities, serotypes of Hantavirus could be differentiated. Thirty-eight
      monoclonal antibodies against Hantaan virus nucleocapsid protein which have
      different cross-reactivities between serotypes were developed. These results
      confirmed the presence of multiple serotype-specific epitopes on the nucleocapsid
      protein of Hantaan virus, which can be utilized in differentiation of serotypes.

PMID- 7583921
TI  - Age-dependent humoral responses of children to mycobacterial antigens.
AB  - In the United States, disseminated infection with environmental mycobacteria,
      including the Mycobacterium avium complex, is the most common opportunistic
      bacterial infection seen in AIDS patients. However, the source and relative
      degree of exposure to environmental mycobacteria during childhood are unknown. To
      examine the age-related exposure to mycobacteria, we obtained serum samples from
      150 children ranging in age from 6 months to 18 years. Each sample was tested
      against both M. avium (serovar 1) sonic extracts and mycobacterial
      lipoarabinomannan, using an enzyme-linked immunosorbent assay (ELISA). All serum
      samples were also subjected to immunoblot analysis with the sonic extract
      antigen. These studies established that elevated ELISA values (P < 0.0001) and
      increased immunoblot reactivity (P < 0.0001) against mycobacterial antigens were
      both associated with increasing age. The seroreactivity differences were most
      striking when comparing the age groups of children below the age of 6 with the
      older age groups. Our results suggest that the development of humoral immune
      responses to mycobacterial antigens in children correlates with increasing age
      and that there may be an environmental factor predisposing to mycobacterial
      exposure which is related to advancing age.

PMID- 7583922
TI  - Oligonucleotide primers designed to differentiate pathogenic pseudomonads on the
      basis of the sequencing of genes coding for 16S-23S rRNA internal transcribed
      spacers.
AB  - Universal primers targeting conserved sequences flanking the 3' end of the 16S
      and the 5' end of the 23S rRNA genes (rDNAs) were used to amplify the 16S-23S
      rDNA internal transcribed spacers (ITS) from eight species of pseudomonads which
      have been associated with human infections. Amplicons from reference strains of
      Pseudomonas aeruginosa, Pseudomonas cepacia, Pseudomonas gladioli, Pseudomonas
      mallei, Pseudomonas mendocina, Pseudomonas pickettii, Pseudomonas pseudomallei,
      and Xanthomonas maltophilia were cloned from each species, and sequence analysis
      revealed a total of 19 distinct ITS regions, each defining a unique sequevar with
      ITS sizes ranging from 394 (P. cepacia) to 641 (P. pseudomallei) bp. Five
      distinct ITS sequevars in P. cepacia, four in P. mendocina, three in P.
      aeruginosa, two each in P. gladioli and P. pseudomallei, and one each in P.
      mallei, P. pickettii, and X. maltophilia were identified. With the exception of
      one P. cepacia ITS, all ITS regions contained potential tRNA sequences for
      isoleucine and/or alanine. On the basis of these ITS sequence data, species
      specific oligonucleotide primers were designed to differentiate P. aeruginosa, P.
      cepacia, and P. pickettii. The specificities of these primers were investigated
      by testing 220 clinical isolates, including 101 strains of P. aeruginosa, 103
      strains of P. cepacia, and 16 strains of P. pickettii, in addition to 24 American
      Type Culture Collection (ATCC) Pseudomonas strains. The results showed that
      single primer pairs directed at particular ITSs were capable of specifically
      identifying the ATCC reference strains and all of the clinical isolates of P.
      aeruginosa and P. pickettii, but this was not the case with several ITS-based
      primer pairs tested for P. cepacia. This pathogen, on the other hand, could be
      specifically identified by primer pairs directed against the 23S rDNA.

PMID- 7583923
TI  - Measurement of sputum antibodies in the diagnosis of acute and chronic
      respiratory infections associated with Chlamydia pneumoniae.
AB  - The aim of this study was to develop methods for the measurement of sputum
      antibodies in the laboratory diagnosis of acute and chronic lower respiratory
      tract infections caused by Chlamydia pneumoniae. Paired serum specimens, sputum
      specimens, and pharyngeal or nasopharyngeal swabs were obtained from 97 patients;
      51 of them had community-acquired pneumonia, and 46 had chronic obstructive
      pulmonary disease (COPD). C. pneumoniae-specific serum immunoglobulin G (IgG),
      IgA, and IgM antibodies were measured by the microimmunofluorescence (micro-IF)
      test. For sputa, specific IgA and IgG antibodies were measured by the micro-IF
      test and secretory IgA (sIgA) was measured by enzyme immune assay (EIA) with C.
      pneumoniae elementary bodies as the antigen. Sputum IgA and sIgA antibodies to C.
      pneumoniae were found, respectively, in 52 and 51% of the COPD patients. Elevated
      levels of stable serum IgG and IgA antibodies (IgG titer of > or = 128 and IgA
      titer of > or = 40), suggesting chronic infection, were found in 54% of the COPD
      patients. The sensitivity for the sputum IgA micro-IF test compared with elevated
      serum antibody levels was 87.5%, and that for the sputum sIgA EIA was 88%; the
      respective specificities were 90 and 95%. Acute C. pneumoniae infection was
      diagnosed in seven pneumonia patients, and two (29%) of these patients were
      positive by sputum EIA antibody measurements. Two pneumonia patients without
      acute infection had stable elevated IgG and IgA levels in their sera, and both of
      them were sputum antibody positive. We conclude that the measurement of IgA
      antibodies to C. pneumonia in sputum is a useful additional diagnostic tool for
      chronic C. pneumoniae infections.

PMID- 7583924
TI  - Anti-human immunodeficiency virus type 1 antibodies of noninfected subjects are
      not related to autoantibodies occurring in systemic diseases.
AB  - Indeterminate Western blot (WB) (immunoblot) patterns for anti-human
      immunodeficiency virus type 1 (HIV-1) antibodies are often observed when testing
      serum samples from noninfected individuals. We investigated here the possible
      involvement of some frequently occurring autoantibodies (anti-SmB/B', U1snRNP [68
      kDa, A, and C], Ro/SS-A [60 and 52 kDa], and Jo-1) in the generation of such
      indeterminate HIV-1 WB. In particular, the role of a reported sequence homology
      between p24 gag and the SmB/B' autoantigen was investigated. Serum samples were
      obtained from 50 healthy controls, 51 patients with systemic lupus erythematosus
      (SLE), 46 with systemic sclerosis, 6 with Sjogren's disease, 3 with mixed
      connective tissue disease, and 41 healthy subjects with persistent indeterminate
      HIV-1 WB. Reactivity to HIV-1 p24 gag was slightly but not significantly more
      frequent in patients with SLE than in controls (25.5% versus 14.0%; P > 0.1),
      whereas reactivity to HIV-1 p17 gag was significantly more frequent in the former
      subjects (23.5% versus 8.0%; P = 0.03). Simultaneous reactivity to p17 and p24
      was observed in patients with SLE (11.8%; P = 0.014) or systemic sclerosis (8.7%;
      P = 0.049) but not in controls. There was no association found between the
      presence of any autoantibody and the occurrence of indeterminate HIV-1 WB nor
      between the presence of p24-reactive antibodies and anti-SmB/B'; this indicates
      that most p24-reactive antibodies are directed to epitopes other than the proline
      rich sequences shared by p24 gag and SmB/B'.

PMID- 7583925
TI  - Interlaboratory variability of CD8 subset measurements by flow cytometry and its
      applications to multicenter clinical trials. NAID/NICHD Women and Infants
      Transmission Study Group.
AB  - Recent studies have demonstrated the utility of measuring subsets of CD8+ T cells
      as prognostic markers in epidemiology cohort studies of human immunodeficiency
      virus (HIV)-infected patients. Most of these studies evaluating the value of CD8+
      T-cell subsets have been performed at single centers, and few data are available
      on variability in the measurement of the CD8+ cell populations in multicenter
      trials. In the current study, we addressed this question by evaluating
      interlaboratory variability from the five laboratories enrolled in the Women and
      Infants Transmission Study sponsored by the National Institutes of Health. This
      study evaluated 35 HIV-positive and 28 HIV-negative proficiency testing samples
      sent to the laboratories for evaluation. The study focused on the robust
      coefficient of variation (RCV) for CD38 (11%), HLA-DR (21%), and CD57 (15%)
      expression on the CD8+ population. Data from the current study indicated that the
      variability in these measurements is greater than that for CD3+ CD4+ (RCV, 5%)
      and CD3+ CD8+ (RCV, 5%) cells. Knowledge of the variability of the CD8+ subset
      measurements should guide investigators in the design and analysis of clinical
      trials and epidemiology studies. Ability to obtain improved interlaboratory
      agreement on CD8+ subset measurements will facilitate further evaluation of these
      markers in HIV studies.

PMID- 7583926
TI  - Multireactive pattern of serum autoantibodies in asymptomatic individuals with
      immunoglobulin A deficiency.
AB  - Selective immunoglobulin A (IgA) deficiency (sIgAD) is associated with certain
      autoimmune states. Increased production of autoantibodies and eventual
      development of overt autoimmune disease are related in part to genetic and
      environmental factors as well as to the immune deficiency. We surveyed serum
      specimens from 60 healthy subjects with sIgAD for the presence of 21 different
      autoantibodies by enzyme-linked immunosorbent assays. The frequencies of 16
      autoantibodies were higher in sIgAD patients than in normal healthy controls.
      Autoantibodies to Jo-1 (28%), cardiolipin (21%), phosphatidylserine (20%), Sm
      (15%), asialo-GM1 (21%), sulfatide (32%), sulfoglucuronyl paragloboside (11%),
      and collagen type I (10%) were detected at high frequencies in comparison to
      those of normal healthy controls. Many of the serum samples were multireactive
      (i.e., exhibited binding to more than two autoantigens). Forty percent (24 of 60)
      of sIgAD serum samples reacted against six or more autoantigens; 10% (6 of 60) of
      sIgAD serum samples were not reactive with any of the 21 autoantigens. Three
      percent (7 of 209) of consecutive serum samples submitted for autoimmune antibody
      analysis that were positive for autoantibodies were from patients with IgA
      deficiency. Our finding of an increased frequency of autoantibodies in sIgAD
      patients supports the notion of polyclonal stimulation by repeated environmental
      stimuli as an etiologic mechanism. Alternatively, the increased frequency may be
      caused by a dysregulation of the immune response in such individuals. The mere
      detection of autoantibodies cannot predict whether a subject with sIgAD will
      develop an autoimmune disease or determine which specific disease will emerge.

PMID- 7583929
TI  - Analysis of immunoglobulin G-binding-protein expression by invasive isolates of
      Streptococcus pyogenes.
AB  - Invasive group A streptococcal isolates collected as part of a Centers for
      Disease Control and Prevention surveillance study were analyzed for expression of
      immunoglobulin G (IgG)-binding proteins. Two IgG-binding phenotypes of group A
      isolates of the M1 serotype were identified. The first group expressed a surface
      protein that bound all four human IgG subclasses (type IIo) and was recognized by
      rabbit anti-serotype M1-specific antiserum but not by normal rabbit serum. The
      second group expressed an IgG-binding protein that was also recognized by the
      anti-serotype M1 antiserum but demonstrated significant nonimmune reactivity only
      with human IgG3 (type IIb). Analysis of extracts of the isolates for reactivity
      with human IgA, fibrinogen, and albumin was also performed. The importance of the
      binding of human plasma proteins to pathogenic group A streptococci remains to be
      established.

PMID- 7583928
TI  - Distinct profiles of immunoglobulin G-binding-protein expression by invasive
      serotype M1 isolates of Streptococcus pyogenes.
AB  - Analysis of immunoglobulin G (IgG)-binding-protein expression by invasive group A
      streptococcal isolates of the M1 serotype collected as part of a Centers for
      Disease Control and Prevention surveillance study revealed two distinct
      phenotypes. One group of type M1 isolates expressed a surface protein reactive
      with all four human IgG subclasses (type IIo), while a second group expressed a
      surface protein demonstrating significant reactivity only with human IgG3 (type
      IIb). The functional forms of IgG-binding protein were antigenically related, and
      both were recognized by a rabbit polyclonal antiserum to serotype M1 but not by
      normal rabbit serum. While the quantities of antigenic M1 protein present in the
      extracts of representative isolates displaying each phenotype differed, the
      functional differences were found to be qualitative and not solely quantitative.
      The IgG-binding properties of these antigenically related M1 proteins could be
      readily distinguished from those of another IgG-binding protein, protein H. Type
      M1 isolates of the IIb phenotype differed from those of the IIo phenotype by
      secreting larger amounts of a casein-hydrolyzing protease into culture
      supernatants.

PMID- 7583930
TI  - Levels of interleukin 6 and tumor necrosis factor in serum from humans vaccinated
      with live, attenuated Francisella tularensis.
AB  - The levels of interleukin 6 (IL-6) and tumor necrosis factor alpha in serum did
      not change significantly during the course of immunization with the live vaccine
      strain of Francisella tularensis. Higher levels of circulating IL-6 were found in
      the sera of vaccinees with good antibody responses than in the sera from
      nonresponders. Preimmunization levels of IL-6 in serum were also higher in
      responders than in nonresponders.

PMID- 7583927
TI  - Cytokine secretion induced by superantigens in peripheral blood mononuclear
      cells, lamina propria lymphocytes, and intraepithelial lymphocytes.
AB  - Superantigens are potent inducers of T-cell proliferation and induce a broad
      range of cytokines, including tumor necrosis factor (TNF), gamma interferon, and
      interleukin 2 (IL-2). In the present study, we compared the abilities of
      different staphylococcal superantigens (staphylococcal enterotoxin B [SEB],
      staphylococcal enterotoxin E [SEE], and toxic shock syndrome toxin 1 [TSST-1]) to
      stimulate distinct cytokine profiles in peripheral blood mononuclear cells
      (PBMC), lamina propria lymphocytes (LPL), and intraepithelial lymphocytes (IEL).
      One million PBMC, LPL, and IEL were stimulated with various concentrations of
      superantigen (10 to 0.001 ng/ml) for 24, 48, and 72 h. Maximum cytokine
      production by PBMC, LPL, and IEL was observed for all three superantigens at 48 h
      at a concentration of 1 ng/ml. In PBMC, SEE and TSST-1 stimulated more IL-2 and
      gamma interferon than SEB. SEE and TSST-1 also stimulated more TNF and IL-4
      production than SEB. In contrast, SEB stimulated more IL-6 than either SEE or
      TSST-1. In LPL, there was no SEE-induced IL-2 or IL-4 production, but IL-6, TNF,
      and gamma interferon were induced. SEB similarly induced no IL-2 or gamma
      interferon from the LPL, but IL-4, IL-6, and TNF were detected. TSST-1
      stimulation of LPL resulted in IL-2 and TNF production but no IL-4, IL-6, or
      gamma interferon. In IEL, SEE induced no IL-2, IL-4, or gamma interferon but
      produced IL-6 and TNF, while SEB stimulation resulted in no IL-2 or gamma
      interferon but did result in detectable IL-4, IL-6, and TNF. Taken together,
      these data indicate that there are significant differences in the cytokine
      profiles induced by superantigens in LPL and IEL compared with those in PBMC, and
      these differences may relate to differences in activation requirements.

PMID- 7583931
TI  - Early appearance of antibodies to simian immunodeficiency virus in saliva and
      serum of infected macaques.
AB  - Simian immunodeficiency virus (SIV) infection in macaques is an important animal
      model for human immunodeficiency virus infection in humans. This study evaluated
      the temporal development of antibodies to SIV in the parotid saliva of macaques
      inoculated with the virus and compared these findings with the development of
      antibodies to SIV in the animals' sera. Three animals (ages, 14, 18, and 18
      years) were inoculated with the macrophagetropic strain SIVmac239. Prior to
      inoculation and at consecutive weekly intervals during a four-week period
      following the initial virus inoculations, parotid saliva and serum were collected
      from each animal. A fourth animal (age, 9 years) served as a negative control,
      and the fifth and sixth animals (ages, 2 and 22 years) served as positive
      controls (6 and 18 months postinoculation, respectively) with SIVmac239. Saliva
      and serum samples were reacted against SIV antigen in Western blots (immunoblots)
      prepared in the standard fashion to determine the presence of antibodies. The
      reactions of these antigen-antibody complexes with biotinylated anti-human
      immunoglobulin A (IgA), IgM, and IgG and biotinylated anti-human secretory
      component (SC) determined the class of antibody present or the presence of SC in
      the original parotid saliva or serum samples. In infected animals, the IgM to SIV
      was detectable in serum and saliva at 13 days, and antiviral IgA and IgG in serum
      and saliva were detectable at 20 to 27 days postinoculation. The antibody to SC
      reacted to saliva from only two animals at 20 and 27 days, and long-term positive
      controls were positive for SC in saliva, indicating that either secretory IgA or
      secretory IgM was present in these samples. Antibodies to SIVmac239 antigens have
      therefore been detected in saliva as early as 13 days postinfection. Saliva may
      be as useful as serum as a diagnostic specimen and/or disease-monitoring method
      in this important animal model.

PMID- 7583932
TI  - Cytokines in the stools of children with complicated shigellosis.
AB  - The pathogenesis of the systemic complications, leukemoid reaction and hemolytic
      uremic syndrome, associated with Shigella dysenteriae type 1 infection is not
      well understood. The excessive production of proinflammatory cytokines, including
      tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), has been
      suggested as a possible factor. We measured IL-6 and TNF-alpha in stools of 56
      children with S. dysenteriae 1 infection and 29 children without any apparent
      infection, all age 12 to 60 months. Sixteen children with S. dysenteriae 1
      infection had leukemoid reaction or hemolytic uremic syndrome (complicated
      shigellosis), while the others did not (uncomplicated shigellosis). Stool IL-6
      and TNF-alpha concentrations were higher in children with uncomplicated
      shigellosis than in children with complicated shigellosis (P = 0.009 and < 0.001,
      respectively) or in uninfected children (P < 0.001). It is concluded that
      complicated infection is not associated with higher concentrations of the
      proinflammatory cytokines IL-6 and TNF-alpha in stool.

PMID- 7583933
TI  - Seroepidemiologic study of three zoonoses (leptospirosis, Q fever, and tularemia)
      among trappers in Quebec, Canada.
AB  - This study was undertaken to evaluate the prevalence of antibodies against
      Francisella tularensis, Coxiella burnetii, and certain serovars of Leptospira
      interrogans among trappers in Quebec, Canada. Muskrat trapping was identified as
      a risk factor for F. tularensis infection, whereas having a cat at home
      apparently protected trappers against infection by L. interrogans. High
      percentages of control sera were positive for antibodies against C. burnetii
      (15%) and L. interrogans (5%), most frequently serovar bratislava. This is the
      first report of human infection by serovar bratislava in North America.

PMID- 7583934
TI  - Bioactive tumor necrosis factor in the sputa of cystic fibrosis patients.
AB  - Eighty sputum samples from 37 cystic fibrosis patients were assayed for tumor
      necrosis factor alpha (TNF-alpha) in the L929 bioactivity assay. In addition, the
      presence of TNF-alpha-specific mRNA in the sputum was determined by using TNF
      alpha-specific DNA probes in a PCR amplification step after reverse transcription
      of the mRNA to cDNA. Bioactive TNF-alpha was detected in 69 (86%) of the 80
      sputum samples tested and, on at least one occasion, in 35 (95%) of the 37 cystic
      fibrosis patients sampled. The highest levels of TNF-alpha were observed in sputa
      obtained from patients presenting with an exacerbation of their disease.

PMID- 7583935
TI  - Immunomodulatory effects of alpha interferon and thymostimulin in patients with
      neoplasias.
AB  - In this report, we have evaluated the immunological effects following
      administration of alpha interferon (IFN-alpha) in combination with thymostimulin
      (TP-1), as well as of IFN-alpha and TP-1 alone in patients with neoplasias who
      underwent surgery and were subsequently treated with conventional chemotherapy.
      Data suggest that the combination of IFN-alpha and TP-1 is the most effective in
      the up-regulation of some immune parameters such as the CD4(+)-CD8+ cell
      dependent antibacterial activity. Since this immune function plays an important
      role in the host protection against different targets such as invading
      microorganisms and/or neoplastic cells, the administration of TP-1-IFN-alpha is
      advisable for patients with neoplasias under chemotherapy.

PMID- 7583936
TI  - Heterogeneity of VP4 neutralization epitopes among serotype P1A human rotavirus
      strains.
AB  - We have used serotype-specific VP4 and VP7 neutralizing monoclonal antibodies (Nt
      MAbs), as well as subgroup (SG)-specific MAbs, to characterize by enzyme
      immunoassay rotavirus strains isolated from diarrheic infants in the city of
      Monterrey, Mexico, from July 1993 to March 1994. Of a total of 465 children
      studied, 140 were rotavirus positive, including 3 patients infected with non
      group A rotaviruses. The SG and VP7 (G) serotype specificities could be
      determined for 118 (84%) of the 140 rotavirus-positive stool specimens; 4
      rotavirus strains were serotype G1 and SGII; 1 strain was serotype G2 and SGI+II;
      112 strains were serotype G3 and SGII; 1 strain was serotype G3 and SGI; and none
      of the strains was serotype G4. Fifty-eight specimens, representing the 13
      different group A rotavirus electropherotypes detected, were chosen for VP4 (P)
      serotyping. Of these, 48 (83%) strains reacted with the P1A serotype-specific Nt
      MAb 1A10. None of the strains reacted with the serotype P2-specific Nt-MAbs
      tested. Not all viruses that reacted with Nt-MAb 1A10 were recognized by Nt-MAbs
      2A3 and 2G1, which also recognize P1A strains, indicating heterogeneity of
      neutralization epitopes among serotype P1A human rotaviruses. This heterogeneity
      could be relevant for the specificity of the VP4-mediated neutralizing antibody
      immune response and indicates the need for antigenic characterization, in
      addition to genomic typing, of the VP4 proteins of circulating human rotavirus
      field strains.

PMID- 7583937
TI  - Rare anorectal pathologic conditions.
AB  - Among the rare anorectal pathologic conditions published in the literature since
      1992, except for malignant pathology, we have taken an interest in anal
      dermatology with Hailey-Hailey disease; infectious diseases, including
      tuberculosis, gangrene, actinomycosis, and cytomegalovirus ulcerations; vascular
      pathology with rectal varices and tumoral pathology with leiomyomas and lipomas;
      embryologic disorders, including gastric and salivary heterotopia; and a few
      exceptional lesions, such as spontaneous hematomas and certain traumatic lesions.

PMID- 7583938
TI  - Preoperative endocrine tumor localization utilizing a cost-effective approach.
AB  - Endocrine tumors commonly produce characteristic clinical signs, and laboratory
      tests lead to accurate diagnosis in a high percentage of cases. The successful
      management of these tumors usually requires complete surgical resection. A large
      number of preoperative localization procedures to facilitate the operative
      management of these tumors have been developed. This report reviews the recent
      contributions to this literature, with a particular emphasis on cost-effective
      use of these procedures.

PMID- 7583939
TI  - Esophageal, gastric, and small intestine.

PMID- 7583940
TI  - Extended resections in the management of esophageal carcinoma.
AB  - The survival rate of patients with carcinoma of the esophagus is dismal.
      Improvement could be achieved only by earlier diagnosis and radical resection
      techniques to remove the esophagus and its draining lymphatic bed. En bloc
      esophagectomy and esophagectomy with three-field lymph node dissection are
      practiced in some centers in North America, Europe, and Japan. Survival rates
      with these techniques are better than those obtained with standard resection
      techniques.

PMID- 7583942
TI  - The role of minimal-access surgery in esophageal disease.
AB  - Modern advances in equipment and techniques have made it possible to treat many
      esophageal diseases with minimally invasive techniques. This chapter describes
      the impact of thoracoscopy and laparoscopy on esophageal surgery, with particular
      emphasis on the technique and results of esophageal myotomy, antireflux
      operations, and esophageal resection.

PMID- 7583943
TI  - Peptic ulcer disease, Helicobacter pylori, and the surgeon: changing of the
      guard.
AB  - The ability to assign causative roles to Helicobacter pylori and nonsteroidal
      anti-inflammatory drug use in peptic ulcer disease, and proof that eradication of
      H. pylori infection results in cure of peptic ulcer disease, are resulting in a
      reassessment of the indications for surgery and the type of surgery to be
      performed. With only a few exceptions, surgery is rapidly becoming an outdated
      approach to the management of peptic ulcer disease. We will soon see the day when
      surgeons with great technical skill in peptic ulcer disease will be rare, just as
      it happened when chest surgeons were no longer needed for the management of
      chronic pulmonary infections.

PMID- 7583941
TI  - Histologic, flow cytometric, and genetic criteria in endocrine surgery.
AB  - Differential diagnosis of endocrine neoplasms as benign or malignant is
      frequently extremely difficult. Similarly, assessing prognosis in cases of
      malignancy is problematic. Traditionally, histologic criteria, including grade of
      the tumor, architectural features, and cytologic appearance, have been used to
      predict biologic behavior. In addition, clinical scoring systems may be useful in
      assigning prognosis in individual cases. Examination of the DNA profile of
      individual cells by flow cytometry may correlate with the aggressiveness of the
      tumor. Recent developments in molecular genetics have yielded genetic markers
      that may be useful in diagnosis and prognosis as well as illuminating the
      pathogenesis of endocrine neoplasia. This review summarizes the status of
      traditional and newer methods of pathologic interpretation of endocrine
      neoplasms. In general, the most accurate assessment of these tumors is derived
      from consideration of a collage of the clinical and pathologic criteria discussed
      herein.

PMID- 7583944
TI  - Incidentally discovered adrenal tumors.
AB  - The introduction of computed tomography has dramatically increased the detection
      and in turn the incidence of incidentally identified adrenal abnormalities; the
      current incidence rate is approximated at 2%. Improvements in technology can be
      expected to increase the reported incidence even further and magnify the clinical
      problem these abnormalities pose. Although most clinicians would agree that
      surgery is indicated in patients with primary adrenal malignancy and those with
      significant endocrine function, strategies for the management of patients with
      incidentally identified lesions remain controversial. One approach is to base the
      risk of primary adrenal malignancy on lesion size and undertake biochemical
      evaluation only for patients who, on clinical grounds, are likely to have
      endocrinopathy. Another approach is to assess endocrine function (biochemically
      and radiographically) in all patients and recommend surgery or additional
      evaluation (eg, needle biopsy) for those found to have abnormalities. Recent
      studies of patients with benign, incidentally discovered adrenal lesions suggest
      that these common lesions are almost all hormonally functional to some extent.
      The natural history of subclinical but functioning adrenal adenomas is not known.

PMID- 7583946
TI  - Preoperative cardiac risk assessment and management.
AB  - Perioperative cardiac morbidity is the leading cause of death following the
      administration of general anesthesia. With the aging of the population, the
      number of patients at significant cardiac risk for noncardiac surgical procedures
      is expected approximately to double over the next 30 years. Assessing cardiac
      risk will assume increasing importance in surgical decisions. Historical
      predictors, diagnostic testing predictors, and recent data concerning
      preoperative cardiac physiology assessment and optimization are discussed.

PMID- 7583945
TI  - Progress in the management of gastric cancer.
AB  - Over the past 30 years, numerous major centers have published analyses of
      potential factors influencing survival following resection of gastric cancer. The
      independent significance of depth of tumor penetration and lymph node status has
      been consistently documented. With proper staging, we know which patients are
      most likely to die of their disease. Unfortunately, adjuvant treatment in
      surgical resection has not altered patient outcome. Emphasis should now be on
      selecting the patients who should receive radical surgery for cure, adjuvant
      therapy with a hope for cure, or palliation. This brief review concentrates on
      recent developments in our ability to stage patients preoperatively, developments
      that may change the way we approach the patient with stomach cancer in the
      future.

PMID- 7583947
TI  - Medical and radiologic evaluation and operative treatment of primary
      hyperparathyroidism.
AB  - The diagnosis of primary hyperparathyroidism (HPT) relies principally on repeated
      measurements of total serum calcium and determination of intact parathyroid
      hormone. A careful patient history and routine blood chemistry will generally
      verify symptoms in the common patient with HPT, who should be a candidate for
      surgery. The operative treatment in primary HPT is efficient, with reported high
      success rate, minimal complications and frequent alleviation of symptoms.
      Nonoperative medical surveillance should preferentially be considered in elderly
      patients with borderline increases in serum calcium of around 2.7 mmol/L or less,
      who in fact constitute a major proportion of hypercalcemic individuals detected
      at population screening. The patients in whom an operation is deferred should
      lack any symptoms or complications associated with primary HPT known to benefit
      from surgery, and this includes the commonly encountered neurobehavioral
      disability. Surveillance may also occasionally be chosen for really old
      individuals, when expected improvement fails to justify operative risks. In
      keeping with the generally liberal indications for parathyroid surgery,
      surveillance may be time limited if the patients develop disability or display a
      rise in serum calcium during follow-up.

PMID- 7583948
TI  - Recent advances in the localization and surgical management of duodenal
      gastrinomas.
AB  - Duodenal gastrinomas are now more frequently recognized as the source of
      hypergastrinemia in patients with Zollinger-Ellison syndrome. The cell lineage of
      duodenal gastrinomas may differ from that of pancreatic gastrinomas, which
      accounts for variations in their clinical behavior. Attempts to localize the
      submucosal tumors are difficult and are limited by their small size.
      Intraoperative endoscopic transillumination, selective intra-arterial secretin
      injection, and duodenotomy with mucosal eversion are currently the most sensitive
      and reliable methods of localization. Endoscopic ultrasonography and somatostatin
      scintigraphy further enhance the accuracy of preoperative localization of these
      tumors. Current information based on cure rates and survival data mandates a
      primary surgical approach in patients with either the sporadic or the multiple
      endocrine neoplasia type 1-associated form of the disease. Thus, wide local
      resection of duodenal gastrinomas with removal of all tumor-bearing lymphatic
      tissue and acid inhibitory pharmacotherapy (proton pump inhibition) may yield 5
      year survival rates of 80% to 90%. Similarly, in patients with pancreatic and
      duodenal gastrinomas as a manifestation of multiple endocrine neoplasia type 1,
      the additional enucleation of pancreatic lesions with or without distal
      pancreatectomy has resulted in cure rates of 67% to 100%.

PMID- 7583949
TI  - Mucosal healing and adaptation in the small intestine.
AB  - The closely related processes of healing and adaptation in the intestinal mucosa
      are of substantial clinical significance in patients after injury, intestinal
      surgery, and inflammatory or infectious ulceration, as well as all patients who
      are fasting. Recent investigations demonstrate that mucosal healing and
      adaptation are complex processes that seem likely to be regulated by a variety of
      autocrine and juxtacrine growth factors as well as conventional gut peptides.
      Further studies of the biology of mucosal healing may permit pharmacological
      intervention to promote healing and adaptation in the future.

PMID- 7583951
TI  - Liver, biliary tract, and pancreas.

PMID- 7583953
TI  - Nonsurgical treatment of liver metastases.
AB  - Experimental studies demonstrate that angiotensin II and somatostatin analogues
      have some ability to redirect hepatic arterial blood flow toward liver
      metastases. Albumin microspheres and liposomes are both effective to animal
      models in enhancing intra-arterial drug delivery to tumor tissue. Clinical
      studies show that such strategies can also improve drug targeting in humans.
      Clinical trials of intrahepatic arterial chemotherapy demonstrate definite
      response and survival benefits, but toxicity can be considerable, and progression
      of extrahepatic disease remains an unsolved problem. Selective means of
      delivering radiation, biologic therapy, and thermal energy to liver metastases
      are possible alternative nonsurgical treatments that merit further investigation.

PMID- 7583950
TI  - Perianal inflammatory conditions in inflammatory bowel disease.
AB  - Perianal complications of Crohn's disease are fairly common in the adult and
      pediatric populations. Transrectal ultrasonography is effective for the diagnosis
      and follow-up of patients with anorectal abscesses and fistulas in Crohn's
      disease. Metronidazole and 6-mercaptopurine therapy have been used effectively to
      treat perianal complications of Crohn's disease in the pediatric population.
      Asymptomatic perianal fistulas in a patient with Crohn's disease do not require
      treatment. If a fistula is symptomatic and involves only a small portion of the
      sphincter mechanism, conventional fistulotomy may be performed with good results.
      Complex fistulas that involve larger areas of the sphincter are best treated by
      optimizing medical management and seton placement. The management of rectovaginal
      fistulas in the presence of Crohn's disease is controversial. Conventional
      fistulotomy and transvaginal mucosal advancement flap with diverting ileostomy
      have been advocated as primary treatment modalities. Rectovaginal fistulas
      secondary to ulcerative colitis may be treated by ileoanal pouch anastomosis and
      primary repair.

PMID- 7583954
TI  - Surgery for sclerosing cholangitis.
AB  - The diagnosis of primary sclerosing cholangitis is made radiologically in
      patients with extrahepatic obstructive jaundice. This condition lacks a known
      cause and another method of diagnosis, and its treatment is palliative
      mechanical, with bypasses, dilation, or orthotopic liver transplantation. Recent
      progress has been seen in stratifying patients with respect to prognosis.
      Stratification is important for conducting clinical trials and for predicting
      which patients should receive a transplant at an earlier, less risky stage in the
      course of the disease. Expandable metal stents are on trial in patients with
      benign or malignant strictures. These newer stents seem to be better than
      polyethylene stents, although their use has not been reported in sclerosing
      cholangitis. With survival data used as a measuring point, relief of jaundice
      does not appear to correlate with increased survival. Of concern has been the
      association of cholangiocarcinoma with sclerosing cholangitis. Cholangiocarcinoma
      is difficult to recognize clinically and has a negative impact on the results of
      transplantation.

PMID- 7583952
TI  - Continence disorders.
AB  - Strategies to evaluate patients with continence disorders continue to evolve at a
      rapid pace. These novel methods quantify physiologic events that, in turn,
      facilitate increasingly accurate discrimination among the causes of incontinence
      and constipation. This review discusses recent advances in the causes, diagnostic
      approaches, and management options available for patients with continence
      disorders.

PMID- 7583955
TI  - Continence-preserving procedures for benign and malignant disease.
AB  - The musculature of the anal sphincter is not involved in ulcerative colitis and
      is seldom invaded directly by rectal carcinoma. Because the sphincter is capable
      of preserving a good degree of continence, even after removal of the entire
      rectum for rectal carcinoma, or even of the entire rectum and colon in ulcerative
      colitis, it should be preserved in most patients who require surgical treatment
      for these conditions. This review is primarily concerned with what type of
      enteric substitute should be used for the excised rectum. It addresses the issues
      of whether retention of a few centimeters of distal rectum above the anal high
      pressure zone (when permissible) is of value in patients with rectal carcinoma;
      whether the entire anal sphincter complex, including the so-called "sampling
      zone" of anal mucosa, should be preserved in the course of rectal excision for
      ulcerative colitis; or whether, alternatively, all mucosa above the dentate line
      should be removed and continuity restored by means of an endoanal, pouch-anal
      anastomosis. For the patient, the eventual clinical result depends on the quality
      of the anal sphincter, the physiologic characteristics of the "neorectum," the
      degree to which anal and rectal function are coordinated, and finally, the
      judgment and technical skill of the surgeon.

PMID- 7583956
TI  - Current status of surgery for Klatskin tumors.
AB  - Klatskin tumors, or hilar cholangiocarcinomas, are an uncommon cause of
      obstructive jaundice. With the advent of sophisticated imaging studies and
      cholangiography, these tumors can be preoperatively identified in most patients,
      and a treatment plan can be outlined before operative exploration. Surgical
      resection of the hepatic bifurcation with the addition of a hepatic lobectomy as
      indicated by tumor extension is the treatment of choice. Although complete
      surgical resection improves survival over that achieved with palliative
      procedures, the 5-year survival rate remains less than 20%. Postoperative
      radiation therapy may increase long-term survival.

PMID- 7583957
TI  - Is there a place for the Kasai procedure in biliary atresia?
AB  - The survival of infants with biliary atresia has improved significantly during
      the past two decades as a result of modification of the Kasai
      hepatoportoenterostomy procedure complemented by advances in liver
      transplantation. Recent reports suggest that the long-term success rate of the
      Kasai procedure is 40%. Failures are salvaged by liver transplantation. Advances
      in organ preservation, the use of reduced-sized grafts, and newer
      immunosuppressive agents (cyclosporine, FK 506) have strongly influenced these
      improved results. Unfortunately, liver transplantation is associated with a high
      complication rate, the risk of opportunistic infection, and an increased rate of
      malignancy due to immunosuppression. Until immunotolerance can be achieved, the
      Kasai procedure remains the procedure of choice for infants with biliary atresia.
      Liver transplantation is a life-saving complementary procedure for patients who
      fail to drain bile following the Kasai procedure, who are older than 3 to 4
      months of age at diagnosis, or who have advanced cirrhosis. In the current era,
      the overall survival should exceed 80%.

PMID- 7583958
TI  - Evaluation of hepatic function.
AB  - Nine articles published since January 1992 on new methods of evaluating hepatic
      function are reviewed. These articles described the clinical significance of
      blood levels of cytokines, fibrin- or fibrinogen-related antigens, vitronectin,
      and endothelin, and of magnetic resonance spectroscopy, methionine metabolism,
      vasopressin clearance, vascular compliance, and radioreceptor imaging in
      gastroenterology. None of the methods have yet been applied to surgery. In
      addition, the redox theory, the evaluation of hepatic mitochondrial redox
      potential by arterial ketone body ratio and its clinical application, is
      introduced, and recent publications on the assessment of graft viability in liver
      transplantation and preoperative hepatic functional reserve in liver surgery
      based on the theory are reviewed.

PMID- 7583959
TI  - Laparoscopic antireflux repair and myotomy.
AB  - Since 1991, the techniques of endosurgical antireflux repair and myotomy have
      been developed for the treatment of gastroesophageal reflux disease and
      esophageal motility disorders. The principles of open surgery for the treatment
      of these conditions learned over several decades should be incorporated into
      minimally invasive approaches. Moreover, proper patient evaluation and selection
      are critical to the success of these procedures. This paper describes the
      technical aspects of endosurgical antireflux repair and myotomy.

PMID- 7583962
TI  - Barrett's esophagus.
AB  - A new stimulus for research into the etiology and pathogenesis of Barrett's
      columnar-lined lower esophagus has been provided by the discovery that Barrett's
      esophagus has a very high prevalence in the general population and that
      adenocarcinoma of the esophagus and cardia is the fastest-growing cancer in the
      United States. Gastroesophageal reflux disease is the single most important
      factor in the pathogenesis of Barrett's esophagus, and duodenal juices may play a
      key role in the development of complications of stricture, ulceration, and
      possibly even malignant degeneration. Treatment is, therefore, aimed at
      abolishing all forms of reflux. Acid suppression, if used, needs to be given in
      massive doses to be effective in gastric hypersecretion and has no effect on
      other constituents of the refluxed material. Antireflux surgery has been shown to
      be superior to all forms of medical treatment. Regression is rare after any
      therapy, but continued surveillance is essential, with increased vigilance in
      patients with dysplasia or DNA abnormalities on flow cytometry. The role of
      cigarettes and alcohol in malignant degeneration is refuted.

PMID- 7583960
TI  - Pancreatic pseudocysts, ascites, and fistulas.
AB  - Recent publications dealing with pancreatic pseudocysts, pancreatic ascites, and
      pancreatic fistulas are reviewed. Terminology relevant to pancreatic pseudocysts
      and other complications of acute pancreatitis is clarified. The natural history
      of pseudocysts is examined. Newer management strategies for these complications
      of pancreatic inflammatory disease are discussed, including percutaneous drainage
      of pseudocysts and the use of octreotide in the management of pancreatic ascites
      and pancreatic fistulas.

PMID- 7583961
TI  - Whole-organ versus islet pancreatic transplantation.
AB  - The goals of pancreatic transplantation are to improve the quality of life for
      the diabetic patient, reverse the metabolic abnormalities of diabetes, and
      prevent the dreaded secondary complications. Although transplantation of the
      whole pancreas is the only therapy that reliably achieves euglycemia, the
      complications associated with this procedure and the need for immunosuppression
      make it undesirable except to a select subpopulation of type I diabetic patients.
      Islet cell transplantation is the exciting alternative; however, insulin
      independence has been achieved in only 10% to 20% of patients. Although advances
      in technology could make islet transplantation the treatment of choice for type I
      diabetic patients, islet transplantation currently remains an experimental
      procedure. Diabetes is not commonly considered a surgical disease, but surgeons
      have made major contributions to its treatment and must remain active in the
      development of new treatment modalities for this debilitating disease.

PMID- 7583963
TI  - Endocrine tumors of the pancreas.
AB  - Pancreatic endocrine tumors are rare, yet can cause significant morbidity due to
      excessive secretion of hormones. Octreotide is effective in reducing the plasma
      concentrations of many of these hormones. The availability of potent H2-receptor
      antagonists and omeprazole has altered the emphasis in patients with Zollinger
      Ellison syndrome away from total gastrectomy and towards resection of the
      gastrinoma for potential cure. Fifty percent of insulinomas and gastrinomas are
      not evident on preoperative imaging studies, despite their sophistication.
      Calcium angiography, endoscopic ultrasonography, isotope-labeled octreotide
      scanning, and injection of methylene blue during secretin angiography are recent
      imaging modalities that have shown promise in the localization of these tumors.
      Intraoperative ultrasound has emerged as the best method for operative detection
      of insulinomas. Duodenotomy and intraoperative endoscopic transillumination are
      especially important in the surgical management of Zollinger-Ellison syndrome
      because 30% to 40% of gastrinomas are located in the duodenum. The management of
      patients with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome
      continues to be controversial. Some advocate an aggressive surgical approach,
      whereas others have had little success in rendering patients eugastrinemic.

PMID- 7583967
TI  - Laparoscopy and endoscopy.

PMID- 7583966
TI  - The surgical treatment of morbid obesity.
AB  - Several new developments promise to improve the lot of the morbidly obese.
      Perhaps the most important of these is the gradual recognition that morbid
      obesity is a serious illness that is not the result of immorality or gluttony but
      is, in most cases, a disabling genetically determined handicap. The second
      advance was the agreement at the National Institutes of Health Consensus
      Conference, March 25-27, 1991 that medical therapies generally fail to control
      severe obesity and that surgery should be considered for those individuals who
      have a body mass index over 40 and, if the comorbidities of obesity, such as
      diabetes or sleep apnea, are present, to consider surgical intervention when the
      body mass index is greater than 35. The third development has been the
      improvement of bariatric surgery, ie, the surgery for morbid obesity, with better
      operations, better quality controls, and rigorous follow-up. This article reviews
      the newer concepts of morbid obesity as a disease, delineates the indications for
      surgery, describes the currently recommended operations, and presents the risks
      and benefits of these procedures.

PMID- 7583964
TI  - Pharyngoesophageal swallowing disorders.
AB  - Pharyngoesophageal dysphagia is chiefly a disorder of the elderly. This review
      examines recent advances in the understanding of the normal physiology of
      oropharyngeal bolus transport. Techniques for the evaluation of symptomatic
      patients are discussed with an emphasis on the complementary nature of manometry
      and videoradiography. The technical limitations of manometry are detailed.
      Therapy for the condition is aimed at the underlying cause, and patients with
      neurologic deficits (largest subgroup of patients) should have a good response to
      myotomy provided they fulfill basic criteria. Surgery for Zenker's diverticulum
      is always necessary, and a short discussion of technique has been included.

PMID- 7583968
TI  - Laparoscopic inguinal herniorrhaphy.
AB  - Traditional open hernia repairs are usually performed as outpatient procedures
      under local anesthesia, with minimal morbidity and low recurrence rates. To be
      widely accepted, any new procedure must at least match current standards of
      performance. This review summarizes the most widely used techniques for
      laparoscopic inguinal herniorrhaphy. Early results of over 1700 cases using these
      techniques are reported. Recurrence was lowest using the total extraperitoneal
      repair. In selected patients, laparoscopic inguinal herniorrhaphy is a safe and
      comparable alternative to standard open repairs.

PMID- 7583965
TI  - Surgical infections: blocking the mediator cascade responsible for sepsis and
      septic shock.
AB  - In conventional usage, "sepsis" denotes a clinical syndrome caused by excessive
      release of a variety of proinflammatory mediators, including tumor necrosis
      factor alpha, interleukin-1, and metabolites of arachidonic acid. Because this
      condition can be precipitated by infectious or noninfectious causes (eg, acute
      pancreatitis), a recent consensus conference has advocated replacing the term
      sepsis with the phrase systemic inflammatory response syndrome. Improvements in
      our understanding of the pathophysiologic basis for systemic inflammatory
      response syndrome have resulted in the development of a number of novel
      approaches for treating, preventing, or limiting its deleterious consequences.
      Although much of this work remains confined to the laboratory, several of these
      approaches are undergoing (or recently have undergone) clinical evaluation. Among
      these are the use of monoclonal antibodies against endotoxin, monoclonal
      antibodies against tumor necrosis factor, recombinant proteins that antagonize
      the effects of or bind to circulating interleukin-1 or tumor necrosis factor, and
      drugs that inhibit the enzyme cyclooxygenase, which is responsible for the
      formation of certain key metabolites of arachidonic acid.

PMID- 7583969
TI  - Laparoscopic and endoscopic management of common bile duct stones.
AB  - The rapid evolution and acceptance of laparoscopic cholecystectomy for the
      management of symptomatic cholelithiasis and acute and chronic cholecystitis are
      unprecedented in modern surgical practice. With rapid advances in laparoscopic
      and endoscopic instrumentation and surgical skills, many surgeons are developing
      minimally invasive techniques and strategies for treating the patient with known,
      suspected, or unsuspected choledocholithiasis. Recent articles describing the
      current status, complications, results, and future directions of laparoscopic and
      endoscopic management of common bile duct stones are reviewed. The role of
      endoscopic retrograde cholangiopancreatography and sphincterotomy, laparoscopic
      exploration of the common bile duct, choledochoscopy, and percutaneous
      transhepatic extraction techniques are discussed.

PMID- 7583972
TI  - Treatment of gastric cancer.
AB  - Progress in techniques of diagnosing gastric cancer has made it possible to
      detect small lesions. Because of this advance, mass screenings for gastric cancer
      have been encouraged. Early gastric cancers have reached more than 30% of all
      gastric cancers at many hospitals in Japan. However, more than 50% of patients
      with gastric cancer have advanced cases. To detect early gastric cancer and to
      treat advanced cancer are both important clinically. This paper reviews studies
      of special interest in these areas.

PMID- 7583971
TI  - Controversies regarding laparoscopic colectomy for malignant diseases.
AB  - Surgical investigators have shown that a hemicolectomy can be done
      laparoscopically. This minimally invasive approach to treat colon cancer
      potentially reduces hospitalization time, hastens return to normal activity, and
      reduces health care costs. Hopefully, all of these favorable outcomes can be
      achieved without compromising cancer control. At present, however, the issues
      regarding laparoscopic colectomy are not clear, and prospective studies are
      necessary to validate that this new procedure is superior to open colectomy.
      Because cancer control might be compromised by this new procedure, laparoscopic
      colectomy should not be accepted by the surgical community because of the allure
      of new technology or the hope that it is equivalent to open colectomy in
      controlling a curable disease. Rather, a randomized trial of laparoscopic
      colectomy compared with open colectomy is needed to prove that cancer control is
      not different and that laparoscopic colectomy is cost-effective.

PMID- 7583970
TI  - Surgical treatment of peptic ulceration.
AB  - Evidence continues to accrue that proximal gastric vagotomy is a safe and
      effective elective operation for duodenal ulcer. Recurrent ulceration remains the
      major shortcoming of the procedure but reoperation is rarely required.
      Laparoscopic surgery for peptic ulcer disease is rapidly evolving with anterior
      seromyotomy and posterior truncal vagotomy emerging as the elective procedure of
      choice. Perforated ulcer can also be treated by laparoscopic techniques in some
      cases. Hemorrhage is often amenable to initial endoscopic control measures, but
      when surgery is required, a definitive acid-reducing operation should be
      employed. Ulcerogenic drug use appears to be responsible for an increasing number
      of emergency interventions for life-threatening peptic ulcer complications,
      although simple closure of perforation due to such drugs may be sufficient
      surgical treatment. Long-term follow-up data suggest that there is a real risk
      increase for gastric remnant cancer development 20 years after partial
      gastrectomy for peptic ulcer but the value of regular endoscopic screening of
      patients at risk has not been demonstrated. The long-acting somatostatin
      analogue, octreotide acetate, has been shown to ameliorate the symptoms of the
      postoperative dumping syndrome markedly, although the mechanism of action remains
      largely unknown.

PMID- 7583973
TI  - The diagnosis and treatment of breast cancer.
AB  - There have been several new developments in breast cancer research. Investigators
      are closer to identifying the breast cancer gene, which may aid in the diagnosis
      and treatment of the disease. The more established routine of screening
      mammography has been questioned by the results of the Canadian National Breast
      Screening Study. Many authors challenge this study's validity. Largely because of
      screening mammography, noninvasive breast cancer is one of the most frequently
      diagnosed types of breast cancer. The treatment options for noninvasive breast
      cancers are discussed along with recent publications. The option of breast
      conserving therapy for early stage cancers is also reviewed. Recent investigators
      have sought to identify the most appropriate patients for breast conservation.
      This overview also discusses treatment options for advanced cancers and the use
      of hormonal therapy for all patients with breast cancer.

PMID- 7583975
TI  - Limb-sparing therapy for soft tissue sarcomas.
AB  - Effective therapy for soft tissue sarcoma of the extremities continues in its
      lengthy evolution from mandatory amputation or radical compartment resection to
      multimodality limb salvage procedures. This current approach typically includes
      preoperative neoadjuvant systemic chemotherapy, followed by negative margin
      surgical resection in conjunction with radiotherapy. The scope and functional
      outcome of these resections has been markedly enhanced by the application of
      microvascular-dependent free tissue transfer techniques. Because of the rarity of
      this tumor system, problems in soft tissue sarcoma receive proportionally less
      attention. Nonetheless, the past year has witnessed several important advances in
      this field, as is discussed.

PMID- 7583976
TI  - Gastrointestinal vascular and ischemic syndromes.
AB  - Among the vascular disorders of the small intestine, two major categories are
      mesenteric ischemia and occult gastrointestinal bleeding secondary to a mucosal
      or muscular lesion. Mesenteric ischemia remains a clinical entity with a high
      mortality. Recent advances in the understanding of the pathogenesis of mesenteric
      ischemia have focused on the role of the neutrophil in modulating reperfusion
      injury. The advent of duplex scanning has provided a noninvasive method to detect
      hemodynamically significant stenoses in the mesenteric vessels. Effective small
      bowel endoscopy remains a critical requirement for endoluminal intestinal
      enteroscopy, and its application has proved of increasing advantage in the
      localization of small intestinal lesions that may be the source of occult
      gastrointestinal bleeding.

PMID- 7583974
TI  - Small bowel tumors.
AB  - Small bowel tumors include adenocarcinomas, carcinoids, lymphomas, and sarcomas,
      as well as a variety of benign polyps, which should be excised to rule out
      malignancy. Although small bowel tumors are traditionally difficult to diagnose,
      a heightened index of suspicion should be combined with improved diagnostic
      techniques to increase yield and decrease delays in identification. The
      management of bioactive carcinoid tumors has rapidly advanced over the past year.
      Increasing experience with the stable somatostatin analogue octreotide has
      enabled regulation of hormonal secretion by these tumors both chronically and
      during acute "carcinoid crisis." In addition, early identification may be
      facilitated by the use of isotopically labeled variants of the compound. Although
      the development of sophisticated pharmacotherapeutic probes has improved the
      management of secretory small intestinal tumors, the prognosis for
      adenocarcinomas, lymphomas, and sarcomas still primarily reflects on the time of
      delay in diagnosis and awaits an improved understanding of the pathobiology of
      these malignant lesions.

PMID- 7583978
TI  - Liver, biliary tract, and pancreas.

PMID- 7583979
TI  - Cellular immunotherapy of cancer.
AB  - Recent developments in the understanding of antigen processing and presentation
      and T-cell receptor recognition of antigens have immediate applications to the
      cellular immunotherapy of cancer. The specific antigens and processed peptide
      sequences responsible for T-cell recognition of some human melanomas have
      recently been identified. T cells with antitumor activity are undergoing genetic
      modification to improve their function and clinical efficacy. In addition, novel
      T-cell constructs are being created with chimeric T-cell receptors that confer
      new tumor reactivities to these lymphocytes. Current understanding of the basic
      processes involved in the immune recognition and destruction of tumors is
      allowing the manipulation of these processes to enhance experimental clinical
      therapies.

PMID- 7583977
TI  - Alternative surgical procedures for primary rectal carcinoma.
AB  - This review summarizes the recent literature on alternative surgical procedures
      for treating rectal carcinoma. After a brief examination of publications on
      preoperative staging, current reports on alternative surgical procedures, from
      local excision to anterior resection and extended resection, are discussed.
      Although radiotherapy and chemotherapy are assuming increasingly prominent roles
      in the management of rectal carcinoma, detailed examination of these therapies is
      beyond the scope of this review.

PMID- 7583980
TI  - Liver transplantation.
AB  - From more than 900 articles in the medical literature, published between August
      1, 1991 and July 31, 1992, 46 were selected for review. During the year of
      review, major international symposiums were held on a new drug, FK506, and
      intestinal transplantation. In addition, at least one new attempt at a unifying
      hypothesis regarding graft adaptation was proposed. Other studies included living
      related donor transplantation, results with transplantation for alcoholics, and
      the controversy regarding the role of liver transplantation for the treatment of
      Budd-Chiari syndrome. Concerns regarding the recurrence of both hepatitis and
      primary hepatic malignancy following liver transplantation were also addressed.
      Two innovative approaches to the treatment of acute liver failure offer exciting
      promise for the future. Other subjects include histologic evaluation of renal
      dysfunction in patients with liver disease, quality of life after
      transplantation, and the proper distribution of precious donor livers.

PMID- 7583981
TI  - Management of nutrition in the critically ill patient.
AB  - Many recent clinical studies focus on the critically ill or injured
      hypermetabolic patient and investigate nutritional factors and regimens that can
      potentially reduce septic complications and improve clinical outcome. In addition
      to better defining the amount and type of nutrients appropriate for this
      population, these studies provide insight into important variables such as route
      of nutrient administration, supplementation of formulas with immune-enhancing (or
      nonimmunosuppressive) nutrients, and anabolic agents that promote increased
      nitrogen retention and lean body mass accumulation.

PMID- 7583982
TI  - Molecular biology and clinical applications to cancer.
AB  - New insights into the genetic changes associated with cancer, the genetic control
      of programmed cell death, and the availability of new tools to study biologic
      problems including targeted gene disruption and quantitative polymerase chain
      reaction have defined new questions and allowed more sophisticated answers in
      studies of fundamental cellular processes. The development of new approaches in
      the clinic, including nascent gene therapies, is rapidly evolving.

PMID- 7583983
TI  - Portal hypertension.
AB  - The treatment of portal hypertensive gastrointestinal hemorrhage has seen many
      new and innovative advances in the past 15 years, including pharmocotherapy,
      sclerotherapy, transjugular intrahepatic portacaval shunt, partial portacaval
      shunt, and hepatic transplantation. Such an array of therapeutic options provides
      great flexibility for the physicians managing this complex disorder. The less
      invasive procedures tend to be associated with higher rates of rebleeding from
      esophageal varices. However, these procedures serve as excellent bridges to
      hepatic transplantation in poor-risk patients. Surgical portasystemic shunts
      offer a permanent solution to portal hypertensive bleeding but also have several
      drawbacks. Standard (end-to-side or side-to-side) portacaval shunts are
      associated with unacceptably high rates of p4rtasystemic encephalopathy because
      of complete diversion of portal flow away from the liver. Selective shunts, such
      as the distal splenorenal shunt, result in maintenance of portal perfusion, but
      this is not lasting in alcoholic cirrhotics. Partial shunting (small-diameter
      portacaval H-graft with collateral ligation) is the most recent addition to the
      surgical armamentarium. This allows for hepatic portal perfusion, thus minimizing
      encephalopathy rates, but it violates the right upper quadrant if the patient is
      a candidate for hepatic transplantation. This large array of treatment options,
      each with its own advantages and disadvantages, permits for careful selection of
      the best modality based on several influencing factors. These include the
      underlying liver disease, the prognosis, the health team's experience, the
      resources available to the patient and the community, and the cost-effectiveness
      of each treatment.

PMID- 7583984
TI  - Primary and secondary hepatic malignancies.
AB  - Hepatic malignancy accounts for a large number of cancer-related deaths
      worldwide. Radiologic evaluation of the liver is critically important in the
      selection of patients for surgical treatment and newer modalities including
      computed tomographic arterial portography and intraoperative sonography show
      promise in the detection of small lesions. Advances in our understanding of the
      segmental anatomy of the liver, studies of intraoperative hepatic ischemia, and
      improved care of patients following major hepatic resections have extended the
      limits of surgical treatment of liver lesions, especially in cirrhotic patients
      with limited functional reserve. Along with hepatitis B, new data suggest that
      hepatitis C is also important as an agent causing hepatocellular carcinoma. In
      addition, the tumor suppressor gene p53 is frequently mutated in aflatoxin
      induced hepatoma. In endemic regions, mass screening for early hepatocellular
      carcinoma appears to increase the surgical cure rate. Resectional surgery remains
      the best treatment for primary liver cancer and, in selected cases, liver
      transplantation is worthwhile. Liver resection for some patients with metastases
      of colorectal origin is now considered standard therapy and studies of regional
      chemotherapy for liver cancer are beginning to show promise. It remains to be
      seen whether adjuvant chemotherapy after liver resection will increase cure
      rates.

PMID- 7583985
TI  - Thrombolytic therapy for acute arterial occlusion.
AB  - The standard treatment of peripheral arterial occlusion has been operative,
      employing embolectomy, thrombectomy, or bypass grafting to restore blood flow to
      the compromised extremity. Intra-arterial thrombolysis has been advocated as an
      initial intervention designed to unmask the anatomic lesion responsible for the
      occlusive event, with a directed or endovascular modality thereafter. Four
      thrombolytic agents are in clinical use: streptokinase, urokinase, recombinant
      tissue plasminogen activator, and acylated plasminogen streptokinase activator
      complex. The agents differ with respect to efficacy of thrombolysis, fibrin
      specificity, and cost. At present, urokinase is the most widely used. Recent
      randomized clinical trials suggest a benefit of thrombolytic therapy in the
      initial management of acute peripheral arterial occlusion, with improved patient
      survival and similar amputation rates compared with immediate open intervention.
      Each modality has its place in specific patient subcategories; the determination
      of which patients are best served by a specific modality awaits the results of
      large clinical trials.

PMID- 7583986
TI  - Multiple organ failure.
AB  - Multiple organ failure remains a leading cause of death in surgical intensive
      care units. This review of multiple organ failure focuses on recent (1990 to
      1992) laboratory and clinical advances related to diagnosis, prognosis, and
      therapy of multiple organ failure and is divided into three parts. First, it
      recasts multiple organ failure into the currently accepted terminology, ie, the
      multiple organ dysfunction syndrome. Second, it examines the strengths and
      weaknesses of three mechanistic hypotheses proposed for the clinical syndrome.
      The three hypotheses focus on the gut, molecular mediators, and the
      microvasculature. Third, it synthesizes those three mechanisms into a single
      paradigm; this unifying paradigm can serve as a framework in which to interpret
      subsequent laboratory and clinical advances.

PMID- 7583987
TI  - Biliary infections.
AB  - The scope and importance of biliary infections from both a clinical and
      scientific perspective is rapidly changing. During this past year, considerable
      attention in the literature has focused on infections that are increasing in
      frequency in the United States and throughout the world, as a result of evolving
      demographics and continued spread of the acquired immunodeficiency syndrome
      epidemic. Pyogenic cholangitis remains a challenge for us to treat and
      significant controversy remains regarding optimal management. The myriad
      hepatobiliary manifestations of human immunodeficiency virus infection have led
      to a resurgence in the interest in parasitic and viral infections. Our
      understanding of infections and their pathogenesis and sequelae has progressed,
      although there are still many important questions that remain unanswered.

PMID- 7583988
TI  - Randomized clinical trial results define operative indications in symptomatic and
      asymptomatic carotid endarterectomy patients.
AB  - Randomized clinical trials on the efficacy of carotid endarterectomy have
      assisted in the selection of patients for operative intervention. Three such
      trials involving symptomatic carotid stenosis have confirmed the value of
      endarterectomy in patients with stenoses 70% or greater. Patients with recent
      transient ischemic attack or nondisabling stroke should be referred for
      noninvasive testing. If the patient's stenosis exceeds a threshold level (50% to
      70% diameter-reducing lesion), arteriography should be performed and prompt
      endarterectomy scheduled, rather than antiplatelet therapy, as the primary means
      of treatment. Furthermore, the results of one clinical trial on asymptomatic
      stenosis have demonstrated benefits for operative intervention in reducing
      neurologic events (transient ischemic attack plus stroke). These data require
      additional confirmation in the analysis of stroke alone, which should be
      available within the next year from another clinical trial. These trials help to
      define indications for operation, and the thorough knowledge of their results has
      become essential to our practices.

PMID- 7583991
TI  - Biliary neoplasms.
AB  - Several large series have been reported describing extensive surgery for
      gallbladder cancer; prolonged survival, however, has not been shown compared with
      more conservative treatment. Although in the case of bile duct tumors, excision
      of adjoining structures might confer some benefit and further improvement might
      be seen by the use of radiotherapy. Accurate preoperative imaging is beginning to
      be beneficial in the selection of patients for the different modalities of
      treatment.

PMID- 7583990
TI  - Ischemic nephropathy as an indication for renal artery reconstruction in
      renovascular hypertension.
AB  - The utility of renal revascularization to control hypertension secondary to renal
      artery occlusive disease is widely recognized. However, revascularization for
      purposes of renal salvage, although performed successfully in many instances, is
      a more difficult issue, owing to the higher morbidity and mortality rates
      associated with operative intervention in an older patient population with
      significant comorbid conditions. It is therefore imperative to appropriately
      select patients who may benefit from revascularization, and the aim of our
      discussion is to aid in this selection process.

PMID- 7583989
TI  - Biliary surgery.
AB  - In the past 2 years, a revolution of unprecedented scope has occurred in biliary
      surgery. Laparoscopic cholecystectomy, first performed in 1987, has now become
      the procedure of choice to treat cholelithiasis. Because laparoscopic surgery
      proliferated in the absence of controlled clinical trials, concerns have been
      raised regarding its complications. This article reviews the technique of
      laparoscopic cholecystectomy, examines its feasibility and complications, and
      discusses the evolving role of intraoperative cholangiography and the approach to
      common bile duct stones. In a separate section, we review the year's literature
      on gallstone pancreatitis and on surgical treatment of benign biliary strictures.

PMID- 7583993
TI  - Surgical therapy in chronic pancreatitis.
AB  - Chronic pancreatitis should be treated medically until a surgically correctable
      complication develops. Incapacitating abdominal pain refractory to medical
      therapy is the most common indication for operation. Preoperative evaluation of
      chronic pancreatitis should include a dynamic computed tomography scan to
      evaluate the pancreas and pancreatic duct. If the pancreatic duct is not seen or
      is not dilated on computed tomography, an endoscopic retrograde
      cholangiopancreatogram should be performed. If the pancreatic duct is dilated
      more than 5 mm, a side-to-side pancreaticojejunostomy should be performed in
      symptomatic patients. If the pancreatic duct is not dilated and all other causes
      of pain have been ruled out, a pylorus-preserving Whipple resection or duodenum
      preserving pancreatic head resection should be performed. Distal pancreatectomy
      is reserved for disease isolated to the tail. Total pancreatectomy is used only
      as a salvage procedure and, whenever possible, should be accompanied by
      autotransplantation of the residual gland or islet cells.

PMID- 7583992
TI  - Complications of acute pancreatitis and their management.
AB  - Severe acute pancreatitis remains a disease with high hospital mortality. In the
      period from 1991 to 1992, several articles dealt with the complicated form of
      acute pancreatitis. There is no question that necrosis of the pancreas and fatty
      tissue in the peripancreatic spaces and particularly secondary infection of
      necrosis are the most important prognostic factors for these patients.
      Indications for surgery and the efficacy of conservative treatment of acute
      pancreatitis (including interventional measures) have not been clearly
      determined. Most surgeons would elect to operate on a patient with multiorgan
      failure caused by infected necrosis, however. Another major question is the type
      of surgery to be performed: closed continuous lavage of the lesser sac and
      retroperitoneal cavities, staged relaparotomy, or open packing. This review
      concentrates on articles pertaining to complicated acute pancreatitis in humans.

PMID- 7583994
TI  - Treatment of pancreatic carcinoma.
AB  - Pancreatic carcinoma remains a significant cause of cancer death worldwide. In
      spite of more effective diagnostic techniques, most patients still have advanced
      and incurable disease when the diagnosis is made. Treatments differ depending on
      the extent of the disease at presentation, but accurate staging preoperatively is
      difficult. The Whipple procedure is now done with an operative mortality of 5% or
      less. More effective means of nonoperative palliation are being developed.
      Adjuvant therapy is still largely ineffective.

PMID- 7583995
TI  - Surgical oncology and tumor immunology.

PMID- 7583996
TI  - Critical care and trauma.

PMID- 7583997
TI  - The techniques and uses of lasers in general surgery.
AB  - This paper presents a brief description of current uses of the carbon dioxide,
      neodymium:yttrium aluminum garnet, and other lasers in common general surgical
      procedures. It focuses on the author's own experiences and includes a review of
      the current literature.

PMID- 7583998
TI  - Peripheral vascular injury.
AB  - Over the past 20 years, the predominant trend in the care of the civilian trauma
      patient has been toward less invasive therapy. Splenic injuries that are now
      being identified with computed tomography scan or ultrasound are managed without
      laparotomy. Similarly, in caring for the patient with potential vascular injury
      of the extremity, the trend has been toward less invasive means of diagnosis and
      therapy. Defining which patients need angiography and how to use duplex scanning
      and pressure indices are still evolving issues.

PMID- 7583999
TI  - The case for wide local excision and regional node dissection for high-risk
      cutaneous melanoma.
AB  - For melanomas less than 1 mm thick, a 1-cm margin is considered adequate by most
      authors. For melanomas 1 to 4 mm thick, the results of the Intergroup Melanoma
      Trial in the United States suggest that a 2-cm margin is adequate. European
      studies indicate that a 1-cm margin may be satisfactory for all melanomas 2 mm
      thick or less. Elective node dissection is not indicated for melanomas less than
      1 mm thick. Survival benefit has not been shown in two prospective studies,
      although retrospective studies suggest that elective node dissection improves the
      survival of patients with intermediate melanomas 1 to 4 mm thick. Elective
      dissection is more likely to benefit patients at high risk of harboring
      microscopic disease in the regional nodes, such as men with melanomas 1 to 4 mm
      thick or women with 2- to 4-mm lesions. For melanomas thicker than 4 mm, elective
      dissection is generally not indicated, except for staging purposes in the context
      of a protocol because the predominant mode of dissemination in this group is
      hematogenous. Therapeutic dissection is indicated in all patients with clinically
      suspicious regional nodes and no evidence of distant dissemination. In doubtful
      cases, a biopsy of the node may be done, to be followed, if the results are
      positive, with the definitive procedure. Although the majority of these patients
      relapse, the surgical treatment offers appreciable 5-year survival rates which
      cannot, at present, be attained by other modalities. Some evidence suggests that
      prompt detection of palpable regional nodes and thorough dissection improve the
      survival rates.

PMID- 7584000
TI  - The case for minimal margins and delayed regional node dissection for high-risk
      cutaneous melanoma.
AB  - Some aspects of the surgical treatment of cutaneous melanoma are still currently
      debated. There is presently a general agreement in favor of a less wide excision
      of primary lesions. Specifically, data coming from a randomized study of the
      World Health Organization (WHO) Melanoma Programme indicates that the width of
      resection has no impact on either disease-free and overall survival of 612 stage
      I entered patients. Opportunity of an elective (ELND) or delayed (DLND) lymph
      node dissection remains much more controversial. Complications, including
      lymphedema, associated with this type of surgery, and no evidence of regional
      lymph node disease in at least 70% of clinical stage I patients submitted to node
      dissection, argue for avoiding ELND. Some studies show a positive value for ELND,
      but they are flawed by biased entry of patients into the ELND group, and
      conclusions are not derived from randomized studies. Two prospective trials show
      that ELND does not improve the prognosis of patients with stage I cutaneous
      melanoma. The results of the WHO study of 553 cases will be evaluable at 20
      years. So far, on the basis of many biologic, clinical, and statistical findings,
      there is no evidence, in our opinion, of a substantial benefit related to ELND.

PMID- 7584003
TI  - Immunologic status of the cancer patient and the effects of blood transfusion on
      antitumor responses.
AB  - For patients undergoing potentially curative surgery for cancer, the
      perioperative period is when they appear to be most vulnerable. The antitumor
      immune response is subjected to a number of iatrogenic insults at this time, not
      the least of which is the surgery itself. Any improvements that can be made by a
      further understanding of the pathophysiology of the events in the perioperative
      period, and the therapeutic interventions to control them, would obviously
      benefit the patient. Over the past 10 years, the desire for such benefits has led
      to the intense investigation of "the blood transfusion effect" in cancer surgery,
      which this article reviews.

PMID- 7584002
TI  - Growth factors and comprehensive surgical care of diabetic wounds.
AB  - In diabetic patients, nonhealing cutaneous ulcers are a significant clinical,
      social, and healthcare problem. Based on more than 10 million diabetic patients
      in the United States and an estimated prevalence of 15% for chronic cutaneous
      ulcers, there are approximately 1.5 million patients with this problem. These
      nonhealing cutaneous ulcers result in a high rate of lower extremity amputations
      in the diabetic population. Patients with diabetes have many complications that
      cause chronic cutaneous ulcers. These include peripheral vascular disease,
      autonomic and sensory neuropathy, impaired host defense against infection, and
      delayed wound repair. To treat diabetic patients with chronic cutaneous ulcers
      effectively all the complicating factors must be addressed. In this review we
      discuss the surgical care of these patients and the use of growth factors in
      combination with a comprehensive treatment algorithm.

PMID- 7584004
TI  - Recent progress in the use of monoclonal antibodies for imaging and therapy.
AB  - Despite their availability since 1975, monoclonal antibodies (MAbs) have failed
      to make a significant impact in the clinical treatment of patients outside of
      diagnostic assays for the measurement of tumor markers. Recently, however,
      studies have appeared demonstrating that MAb-directed imaging techniques may have
      a meaningful role to play in the diagnosis and treatment of patients with solid
      tumors such as colorectal cancer and malignant melanoma. Furthermore, second
      generation MAbs are appearing that mediate more specific binding characteristics,
      and experimental studies have suggested that genuine antitumor activity may not
      be far away. Finally, the recent development of newer molecules, such as chimeric
      and human antibodies, may lead to significant advances in MAb use. Specifically,
      allergic reactions to murine antibodies can be reduced or avoided altogether, and
      repeated doses can be administered safely. These newer MAbs appear to mediate
      cell lysis more efficiently and have been combined with chemotherapeutic agents
      and cell toxins. Greater understanding of host responses to MAbs and the
      development of anti-idiotype and anti-anti-idiotype antibodies have led to
      clinical trials that, it is hoped, will confirm the place of MAb therapy in
      clinical oncology.

PMID- 7584001
TI  - Early invasive carcinoma of the breast.
AB  - Breast carcinoma remains the most common malignancy and the second leading cause
      of cancer deaths among adult women in the United States. The benefits of early
      detection by screening mammography continue to be demonstrated. Fine-needle
      aspiration biopsy has become established as a highly accurate and cost-effective
      diagnostic tool that may supplant open surgical biopsy of even nonpalpable breast
      lesions. The safety and efficacy of breast conservation treatment for early
      invasive carcinoma continue to be affirmed. Analysis of several issues in
      management indicate no proven benefit for any different or less aggressive
      locoregional treatment of early "minimal" or "microinvasive" disease than that
      applied to later more established forms of invasive breast carcinoma. These
      frontiers in our understanding of the biology, diagnosis, and treatment of breast
      carcinoma can best be advanced through scientific investigation of this disease.

PMID- 7584005
TI  - New diagnostic techniques in trauma.
AB  - Advances in diagnostic and therapeutic interventions originally intended for use
      under elective circumstances have been applied to the trauma victim. This review
      examines the use of three of these techniques--transesophageal echocardiography
      (TEE), laparoscopy, and thoracoscopy--in the evaluation and treatment of the
      trauma patient. Initial experiences with TEE show it to be superior to
      transthoracic echocardiography in the evaluation of the heart. In limited
      studies, TEE appears to have the sensitivity to use as a screening tool for
      aortic disruption; however, it is severely limited by its ability to evaluate the
      distal aorta only. TEE cannot be used to visualize the ascending aorta or
      brachiocephalic vessels, which may account for 15% to 20% of injuries. Use of
      laparoscopy has been reported in more than 350 patients. Its primary use appears
      to be in decreasing negative and nontherapeutic laparotomies associated with
      penetrating trauma. The ability to operate through the scope continues to
      increase as additional improvements in instrumentation are introduced.
      Thoracoscopy has recently been shown to be able to evacuate retained hemothoraces
      and even drain empyemas and decorticate the pleural cavity.

PMID- 7584006
TI  - Trauma systems, shock, and resuscitation.
AB  - This review of early care covers issues pertaining to the analysis of system
      function, prehospital intravascular volume replacement, diagnosis of proximity
      vascular injury, the role of emergency thoracotomy, and the value of
      transesophageal echocardiography. The first six articles deal with various
      aspects of system function, from triage to analysis of outcome. The next series
      of articles reviews work in progress evaluating optimal fluid for resuscitation.
      Hypertonic saline and dextran combinations have been shown to restore vital signs
      better than isotonic solutions; they are safe, require smaller volumes, and may
      improve head injury outcome. Danger lies in the restoration of perfusion without
      hemorrhage control. Two articles on emergency thoracotomy review the indications
      and outcome in blunt and penetrating trauma. Survival in blunt trauma is
      virtually zero. An article and two editorials summarize state of the art for
      diagnosis and treatment of proximity vascular injury. Two articles describe the
      potential use of the new technique of transesophageal echocardiography. This new
      modality has not formed a solid indication at present and can be considered
      investigational in trauma care.

PMID- 7584007
TI  - Advances in the treatment of pediatric trauma.
AB  - Injury is the leading cause of death among US children over 1 year of age. The
      financial burden of acute care is over $15 billion annually. The unique anatomic
      and physiologic differences of children predispose them to certain types of
      injuries and require a specialized approach to pediatric trauma care. This
      article reviews the common etiologies of injuries to children and identifies
      injury subgroups at increased risk of mortality. Resuscitation and assessment are
      discussed, emphasizing fluid management, rapid intravenous access, and the
      physiologic evaluation of the child in shock. Protocols for evaluating head,
      thoracic, abdominal, and pelvic injuries are presented in light of recent
      advances in the diagnosis, treatment, and rehabilitation of children sustaining
      these injuries.

PMID- 7584008
TI  - Advances in the management of musculoskeletal trauma.
AB  - During the past year, several important advances have occurred in the diagnosis
      and treatment of orthopedic trauma. The increased use of magnetic resonance
      imaging in the diagnosis of acute cervical spine injuries has enhanced the
      ability to treat these patients. The development of better fixation systems for
      the lumbar spine, particularly pedicle screw systems, has increased our ability
      to stabilize and decompress fractures and fracture-dislocations in this region.
      New techniques for pelvic stabilization have proved useful in the treatment of
      these complex injuries. In extremity trauma, the association of compartment
      syndrome with intramedullary nailing has gained more attention and more
      aggressive treatment is advocated for fractures secondary to penetrating trauma.

PMID- 7584009
TI  - The role of total thyroidectomy in the management of differentiated thyroid
      cancer.
AB  - The extent of surgical resection required in the optimal management of
      differentiated (papillary and follicular) thyroid carcinoma remains
      controversial. Arguments in favor of total thyroidectomy include the adequate
      treatment of tumor multifocality, reduction in local recurrence rates and
      anaplastic transformation, and creating a suitable environment for radioactive
      iodine scanning and treatment of metastases. The benefits of this procedure have
      to be weighed against the potential but minimal morbidity.

PMID- 7584012
TI  - Visceral injury.
AB  - Trauma is a major health and social problem. It is the leading cause of death for
      those under age 45, and is a major expense to society, in terms of direct medical
      expense and lost wages. Visceral injury continues to be a major cause of
      morbidity and mortality in the overall trauma picture. This article reviews the
      significant developments in the diagnosis and management in specific areas of
      visceral injury.

PMID- 7584010
TI  - Advances in neurotrauma.
AB  - Neurotrauma advances in 1992 include further elucidation and understanding of the
      pathophysiologic processes involved in head and spine trauma, major contributions
      from multicenter clinical pharmacologic trials, and significant refinement of
      acute management principles. This article integrates the neurotrauma advances of
      1992 in the context of the daily treatment of patients with head and spinal cord
      injuries.

PMID- 7584011
TI  - Genetic aspects of multiple endocrine neoplasia types 1 and 2.
AB  - Multiple endocrine neoplasia (MEN) type 1 is an autosomal, dominantly inherited
      predisposition to develop neoplastic lesions of the parathyroid glands, the
      neuroendocrine pancreas-duodenum, and the anterior pituitary. The genetic defect
      was mapped to the centromeric part of the long arm of chromosome 11 based on
      studies of somatic deletions in MEN-1-associated tumors and linkage analysis in
      families in whom the disease is segregated. Combined family and tumor analysis
      has shown that tumorigenesis in MEN-1 involves loss of the wild-type chromosome,
      indicating that the putative MEN-1 gene is a tumor suppressor gene. Similar
      deletions are also seen in a proportion of sporadic parathyroid and pancreatic
      tumors, suggesting that tumorigenesis involves related mechanisms in both
      sporadic and familial cases. Based on results from linkage analysis in more than
      40 MEN-1 families, predictive testing for MEN-1 using DNA polymorphisms can now
      be performed with high accuracy. Hence, biochemical screening programs can focus
      on individuals at risk to identify early signs of tumor development. MEN-2, an
      autosomal dominant cancer syndrome of variable expressivity, has previously been
      localized to chromosome 10q11.2 by positional cloning tactics. The RET
      protooncogene mapping to the MEN2 susceptibility locus has recently emerged as a
      candidate gene for MEN-2A. RET, a transmembrane receptor protein, has a large
      glycosylated extracellular domain containing clustered cysteine residues and
      calcium-binding motifs, a single hydrophobic transmembrane domain, and a
      cytoplasmic domain with tyrosine kinase catalytic activity. Several germline
      missense mutations in a codon specifying one of these highly conserved cysteine
      residues have been detected in patients affected with MEN-2A.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7584013
TI  - The place for curative surgical procedures in the treatment of sporadic and
      familial Zollinger-Ellison syndrome.
AB  - The surgical treatment of patients with the Zollinger-Ellison syndrome has
      undergone a dramatic evolution since the syndrome was originally described. It is
      now recognized that an aggressive surgical approach is mandatory because of the
      malignant potential of gastrinomas in both the sporadic and the familial forms of
      the syndrome. Although initially regarded as an incurable neoplasm, it is now
      known that complete surgical resection of gastrinomas can result in eugastrinemia
      even in the presence of lymph node metastases. It is now recognized that
      extrapancreatic gastrinomas are more common than pancreatic gastrinomas, and the
      most common location for an extrapancreatic gastrinoma is the duodenal wall.
      Major improvements in preoperative imaging and intraoperative localization
      techniques combined with an increased awareness of the anatomic distribution of
      gastrinomas have markedly increased the surgeon's ability to care for and cure
      patients with the Zollinger-Ellison syndrome.

PMID- 7584014
TI  - The management of acute respiratory failure.
AB  - The mortality rate of severe respiratory failure in most centers remains 60% to
      90% with conventional pulmonary support techniques. Recent advances in the
      physiologic management of patients with acute respiratory failure include
      optimizing systemic oxygen delivery as reflected by continuous mixed-venous
      saturation monitoring, avoidance of the damaging effects of high inflation
      pressures and volumes during mechanical ventilation, and the increasing
      application of extracorporeal life support techniques for refractory respiratory
      failure. The future promises the routine clinical application of novel support
      techniques including implantable intracorporeal gas exchange devices and
      perfluorocarbon liquid ventilation.

PMID- 7584015
TI  - Regulation of protein metabolism during stress.
AB  - Stress induces a hypermetabolic state of increased urinary nitrogen loss and
      increased metabolic rate. The principal reason for such a response is the
      mobilization of amino acids and the production of glucose to provide energy for
      the cells involved in the host immune response and wound repair. The endocrine
      hormones, eg, cortisol, the catecholamines, and glucagon, are largely responsible
      for these effects. Insulin and growth hormone administration can produce anabolic
      effects to block the loss of body protein. Administration of specific amino
      acids, such as glutamine, also appears to be beneficial. However, the
      hypermetabolic state goes beyond derangement of endocrine hormone levels.
      Although the cytokines are also important mediators, it is not clear how these
      mediators, in concert with hormonal changes, produce all of the manifestations of
      the hypermetabolic state seen in stress.

PMID- 7584016
TI  - Colorectal.

PMID- 7584018
TI  - Screening for colorectal cancer.
AB  - This paper reviews studies on fecal occult blood testing and sigmoidoscopy
      screening for colorectal cancer. Recently published data from a randomized
      controlled trial provides the first concrete evidence that annual screening for
      fecal occult blood can reduce colorectal cancer mortality by at least 33%. These
      results are corroborated by a nonrandomized but controlled study that showed a
      43% colorectal cancer mortality reduction with early detection through fecal
      occult blood testing and sigmoidoscopy, and by a case-control study that showed a
      31% colorectal cancer mortality reduction associated with fecal occult blood
      testing. Persuasive data to support screening recommendations for sigmoidoscopy
      are not yet available; however, results from observational studies are suggestive
      and should stimulate further research to assess the benefit of sigmoidoscopy
      screening.

PMID- 7584017
TI  - Lipid fuel metabolism in health and disease.
AB  - Rates of adipose tissue lipolysis are increased in critically ill patients, thus
      increasing the systemic supply of free fatty acids. This increase in the
      availability of free fatty acids is probably mediated by various factors
      including increases in counterregulatory hormones and tumor necrosis factor
      alpha. The cytokines tumor necrosis factor and interleukin-1 also promote de novo
      lipogenesis in the liver and may be responsible for impaired triglyceride removal
      in peripheral tissues; these effects together contribute to the
      hypertriglyceridemia often seen in septic states. This hypertriglyceridemia may
      have a teleologic basis, because triglyceride-rich lipoproteins have been shown
      to bind and inactivate endotoxin. When present in excess, free fatty acids may be
      responsible for tissue injury in the cold-stored liver allograft, in ischemic
      reperfusion cardiac injury, and in ischemic brain injury. Hypoketonemia commonly
      occurs in septic states and may be due to the combination of a defect in hepatic
      ketogenesis and accelerated ketone body uptake by peripheral tissues. Both tumor
      necrosis factor and interleukin-1 have a hypoketonemic effect in animals. Whether
      ketone bodies have significant protein-sparing properties remains controversial.

PMID- 7584019
TI  - Nutrition and the gut mucosal barrier.
AB  - That the gastrointestinal tract performs important immunologic, metabolic, and
      barrier functions, in addition to nutrient digestion and absorption, has recently
      become clear, as have the potential deleterious consequences of loss of mucosal
      barrier function. Because of the potentially important relationship between
      nutrition and gut barrier function, this area has received increasing clinical
      and experimental attention over the past several years. Consequently, this review
      focuses on how nutrition can modulate the integrity of the gut mucosal barrier.
      Special attention will be given to the biology of normal intestinal barrier
      function, as well as to studies investigating the role of nutritionally related
      variables on the gut mucosal barrier.

PMID- 7584021
TI  - Critical care and trauma.

PMID- 7584020
TI  - Adjuvant radiation for rectal cancer: when and with what?
AB  - This review outlines the progress made in recently reported trials to establish
      an effective adjuvant treatment for the surgical management of rectal cancer.
      Many of the trials of preoperative and postoperative radiation conducted over the
      past two decades are now mature. Moderate-to-high doses of radiation given prior
      to or following surgery reduce pelvic tumor recurrence rates but have little
      effect on survival. The coupling of radiation with cytotoxic chemotherapy,
      particularly 5-fluorouracil-based protocols, has been reported to improve
      survival as well as reduce the risk of recurrence in the pelvis and elsewhere.
      The status of ongoing trials is outlined.

PMID- 7584022
TI  - Malnutrition, injury, and the host immune response: nutrient substitution.
AB  - Improvements in surgical management and intensive care therapy have enabled many
      patients to initially survive severe life-threatening trauma or major surgical
      procedures only to die after delayed bouts of sepsis. This paper reviews
      literature published within the past year on the effects of nutrient substitution
      on malnutrition, injury, and the host immune response. Topics discussed include
      immunodeficiencies in trauma and malnutrition, immunomodulation by nutrition, and
      parenteral versus enteral nutrition. We also discuss the roles of arginine,
      glutamine, omega-3 fatty acids, and dietary nucleotides in the host immune
      response.

PMID- 7584023
TI  - Sensitivity versus cost effectiveness in postoperative follow-up for colorectal
      cancer.
AB  - The incidence of colorectal cancer is increasing. Approximately 20% of patients
      present with untreatable, disseminated disease. The remaining 80% are generally
      treated by intended curative resection. Unfortunately, about 40% of the Dukes B2
      and C patients will develop recurrent disease. Of these patients, about one third
      will develop hepatic metastases, one fifth pulmonary metastases, one fifth intra
      abdominal metastases, one tenth retroperitoneal metastases, and one twentieth
      anastomotic recurrences. Rectal cancer patients may have pelvic recurrence rates
      as high as one third. Unfortunately, only about one fifth of the Dukes B2 and C
      patients will initially develop recurrences at only one site and are, thus,
      potentially curable. Indeed, when considering all colorectal cancer patients,
      resectable recurrences will be detected in the liver in only 2%, regional
      recurrences in about 10%, in the lungs in 2%, anastomotic recurrences in less
      than 1%, and in the ovaries in 1%. In general, long-term survival can be achieved
      in about 30% of these patients with salvage surgery. The goal of intensive follow
      up programs has been to identify these sole site recurrences at an earlier,
      asymptomatic stage and thereby improve survival. Unfortunately this laudable goal
      has not been achieved. Intensive (and expensive) follow-up programs consistently
      achieve long-term survival in 0% to 4% of patients. Reliance on symptoms,
      however, achieves remarkably similar end results.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7584024
TI  - Systematic sequencing of the 180 kilobase region of the Bacillus subtilis
      chromosome containing the replication origin.
AB  - We have determined a 180 kb contiguous sequence in the replication origin region
      of the Bacillus subtilis chromosome. Open reading frames (ORF) in this region
      were unambiguously identified from the determined sequence, using criteria
      characteristic for the B. subtilis gene structure, i.e., starting with an ATG,
      GTG or TTG codon preceded by sequences complementary to the 3' end of the 16S
      rRNA. Four rRNA gene sets, 7 individual tRNA genes and 1 scRNA gene were
      identified, occupying 20 kb in total. In the remaining 160 kb region, 158 ORFs
      were identified, suggesting that 1 ORF is coded on average by 1 kb of DNA of the
      B. subtilis genome. Among the 158 ORFs, the functions of 48 ORFs were assigned
      and those of 11 ORFs are suggested through significant similarities to known
      proteins present in data banks. However, the functions of more than half of the
      ORFs (63%) remain to be determined.

PMID- 7584028
TI  - Prediction of the coding sequences of unidentified human genes. I. The coding
      sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly
      sampled cDNA clones from human immature myeloid cell line KG-1 (supplement).

PMID- 7584029
TI  - Multi-gene family of major surface glycoproteins of Pneumocystis carinii: full
      size cDNA cloning and expression.
AB  - The major surface glycoprotein (MSG) of Pneumocystis carinii plays a crucial role
      in the fatal pneumonia caused by this organism in AIDS patients. A cDNA encoding
      a full-length MSG polypeptide was isolated from a lambda library of rat-derived
      P. carinii cDNAs. The deduced MSG, referred to as the MSG5 subtype, is a 120,765
      Da protein composed of 1,076 amino acids and contains an anchoring hydrophobic
      sequence at the C-terminus of the protein. Sequence analyses of cloned MSG-cDNAs
      revealed an MSG-gene family with approximately 70% protein sequence identity
      between subtypes. P. carinii karyotype hybridization analyses indicated that the
      MSG gene family members are scattered throughout most of the P. carinii
      chromosomes. These recombinant MSG proteins reacted with the antiserum from P.
      carinii-infected rats, as expected, and antiserum generated against P. carinii
      infected mice, indicating the existence of common determinants in MSG
      polypeptides. The family of MSG proteins is rich in cysteine residues and these
      cysteines are highly conserved in all MSG subtypes regardless of species
      specificity, suggesting the structural and/or functional importance of these
      cysteines. The pathobiological significance of the MSG gene family and its
      sequence diversity in P. carinii is discussed.

PMID- 7584030
TI  - Cloning and mapping of telomere-associated sequences from rice.
AB  - We have isolated three telomere-associated sequences from rice using cassette
      ligation-mediated polymerase chain reaction (PCR). Each of the obtained clones
      hybridized to the terminal of one or several rice chromosome arms. The telomeres
      recognized by the clones displayed a high level of polymorphism between two rice
      varieties, Nipponbare (a japonica variety) and Kasalath (an indica variety).
      Variability in the chromosome termini was also detected among individual F2
      progeny plants, which were derived from a cross between the two rice varieties.
      One clone containing telomere-associated sequences was located to one end of
      chromosome 5, and another clone to one end of chromosome 11. For another clone,
      non-allelic segregation of polymorphic hybridization bands was observed between
      japonica and indica rice; this clone was mapped to one end of chromosome 12 in
      japonica and to one end of chromosome 11 in indica rice. This indicates an
      exchange of termini between nonhomologous chromosomes.

PMID- 7584025
TI  - Characterization of cDNAs induced in meiotic prophase in lily microsporocytes.
AB  - To identify and analyze genes functioning during reproductive cell formation in
      higher plants, cDNAs harboring the messages induced in meiotic prophase were
      isolated and characterized. A cDNA library constructed from microsporocytes in
      meiotic prophase of Lilium longiflorum was screened with a subtraction probe
      specific to meiotic prophase. Clones selected were classified into 18 groups by
      cross hybridization and partial sequencing. Northern blot analysis revealed that
      the transcripts corresponding to the respective cDNA groups began accumulating at
      the early stages of meiosis and exhibited clone-specific profiles during meiosis
      and the spore formation process. The amino acid sequences of the predicted gene
      products showed similarity with known gene products, e.g. heat shock proteins,
      serine proteases in Bacillus, and RAD 51 gene product in yeast. Half of the
      putative gene products had hydrophobic N-terminal regions, suggesting that they
      may function as signal peptides.

PMID- 7584032
TI  - Sixty new STSs (sequence-tagged sites) of human chromosome 21.
AB  - From human chromosome 21-specific libraries, 22 SfiI linking clones and 38 P1
      clones were isolated and regionally mapped on the chromosome. The terminal
      sequences of these clones were determined and pairs of PCR primers were generated
      which could specifically amplify the sequenced regions. These sequence-tagged
      sites (STSs) should be useful for constructing a high resolution map of human
      chromosome 21.

PMID- 7584026
TI  - Prediction of the coding sequences of unidentified human genes. I. The coding
      sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly
      sampled cDNA clones from human immature myeloid cell line KG-1.
AB  - We established a protocol for the prediction of the coding sequences of
      unidentified human genes based on the double selection and sequence analysis of
      cDNA clones with inserts carrying unreported 5'-terminal sequences and with
      insert sizes corresponding to nearly full-length transcripts. By applying the
      protocol, cDNA clones with inserts longer than 2 kb were isolated from a cDNA
      library of human immature myeloid cell line KG-1, and the coding sequences of 40
      new genes were predicted. A computer search of the sequences indicated that 20
      genes contained sequences similar to known genes in the GenBank/EMBL databases.
      The sequences of the remaining 20 genes were entirely new, and characteristic
      protein motifs or domains were identified in 32 genes. Other sequence features
      noted were that the coding sequences of 23 genes were followed by relatively long
      stretches of 3'-untranslated sequences and that 5 genes contained repetitive
      sequences in their 3'-untranslated regions. The chromosomal location of these
      genes has been determined. By increasing the scale of the above analysis, the
      coding sequences of many unidentified genes can be predicted.

PMID- 7584031
TI  - Chromosomal assignments of novel genes expressed in HL60 granulocytes.
AB  - By collecting 3'-directed cDNA sequences called gene signatures (GSs) on a large
      scale, it is possible to make an expression profile of genes in a particular
      tissue, as well as discovering a number of novel genes. A total of 305 novel GSs
      collected from granulocytoid cells derived from HL60, a human promyelocytic
      leukemia cell line, by exposure to dimethyl sulfoxide were radiolabeled and used
      for Southern blot analyses to determine the copy number of the corresponding
      genes. Of these, 198 GSs identified as representing single-copy genes were then
      used as probes for hybridization analyses using a monochromosomal hybrid cell DNA
      panel. Sixty-nine of them were assigned to individual chromosomes. These results
      demonstrate that the chromosomal distribution of the GSs seems not to be
      proportional to the cytogenetic length of each chromosome.

PMID- 7584033
TI  - Construction of an equalized cDNA library from human brain by semi-solid self
      hybridization system.
AB  - A cDNA library enriched in clones for mRNA species (an equalized cDNA library)
      was constructed from human brain employing semi-solid self-hybridization system
      and cDNA amplification by in vitro transcription. Sequence analysis of the clones
      in the cDNA library indicated that (1) clones representing abundant species such
      as those of mitochondrial origin and expression sequence taq (EST) are
      drastically reduced in their proportion compared to the original library and (2)
      clones representing rare mRNA species or which do not have matched sequences in
      the database increased substantially in their proportion. cDNA libraries thus
      constructed, therefore, are a good source for cloning of cDNA for rare mRNA
      species from specific mammalian tissues and also for direct expression cloning
      since the inserts maintained their original molecular sizes after equalization.

PMID- 7584027
TI  - An expression profile of active genes in human colonic mucosa.
AB  - An expression profile of genes active in the human colonic mucosa was obtained by
      collecting 959 partial sequences from a 3'-directed cDNA library. Seven genes
      were found to produce mRNA each of which comprised more than 1% of total mRNA.
      Four of these genes are novel, and are likely to be uniquely expressed in the
      colonic mucosa, and the other three have been identified as genes for fatty acid
      binding protein, immunoglobulin lambda chain, and carcinoma-associated antigen
      GA733-2. In the remaining 952 clones, 310 were composed of 118 species occurred
      recurrently but less than 1%, and 533 clones appeared only once. Because the 3'
      directed cDNA library faithfully represents the mRNA population in the source
      tissue, these numbers represent the relative activities of the gene expression.
      Altogether 156 gene species were identified in GenBank, and a significant portion
      of these genes encode proteins found in Golgi apparatus and lysosomes, chromosome
      encoded mitochondrial proteins, cell surface proteins, and components in the
      protein synthesis machinery. The types and proportions of genes identified is
      consistent with the known major activities of the colonic mucosa such as mucous
      protein production, energy-dependent water absorption, and rapid cell
      proliferation and turnover.

PMID- 7584034
TI  - Nucleotide sequence of a putative sensory kinase gene from the cyanobacterium,
      Anacystis nidulans 6301.
AB  - The nucleotide sequence of a 2,146 bp portion of the Anacystis nidulans
      (Synechococcus PCC6301) genome has been determined. This region contains an open
      reading frame (ORF) of 392 codons, whose predicted protein sequence shows partial
      homology to those of E. coli phoM and envZ. Hence ORF392 is suggested to be a
      sensory kinase gene in cyanobacteria.

PMID- 7584035
TI  - Application of the RLGS method to large-size genomes using a restriction trapper.
AB  - We developed a method for producing restriction landmark genomic scanning (RLGS)
      profiles of large-size genomes, such as those of higher plants or amphibians
      using a restriction trapper. Use of the conventional RLGS method is limited to
      genomes smaller than 3 x 10(9) bp, because the larger genomic DNAs, especially
      those of more than 1 x 10(10) bp, produce high background due to incorporation of
      radioactivity at non-specifically damaged sites. Our new method reduces the
      background levels by reducing genome complexity to 1/200-1/300 using a
      purification step to enrich DNA fragments carrying specific restriction landmarks
      at their ends using a restriction trapper. This step makes it possible to obtain
      RLGS patterns of larger genomes. Our paper describes the practical application
      for the RLGS method using a restriction trapper with the pine tree genome (3 x
      10(10) bp/haploid genome; Pinus koraiensis Sieb. et Zucc.) as an example.

PMID- 7584037
TI  - Determination of Gardnerella vaginalis genome size by pulsed-field gel
      electrophoresis.
AB  - The chromosomal DNA of four strains of Gardnerella vaginalis were digested with
      rare cutting restriction enzymes and analyzed by pulsed-field gel electrophoresis
      (PFGE). The four strains studied were two clinical isolates (GVP 004 & GVP 007)
      and two American Type Culture Collection strains (ATCC 14018 & ATCC 14019). The
      restriction enzyme SfiI generated two DNA fragments of about 0.6 Mb and 1.1 Mb in
      all four strains giving a G. vaginalis genome size of about 1.7 Mb. A similar
      genome size was calculated utilizing two more GC-rich sequence specific
      restriction endonucleases, NotI and AscI. When digested with AscI, the
      chromosomal DNA of all four strains gave rise to 11 to 12 DNA fragments ranging
      between 0.01 Mb to 0.43 Mb. DNA from the two clinical isolates were digested by
      NotI (yielding 7 to 9 fragments), while the DNA from the two ATCC strains were
      resistant to NotI digestion. In contrast the clinical isolates, DNA from the two
      ATCC strains gave an identical profile for all restriction endonucleases tested.
      From double digestion experiments, the two SfiI sites could be localized on two
      AscI fragments. From these PFGE studies, it is concluded that the G. vaginalis
      genome is a circular DNA that ranges between 1.67 Mb and 1.72 Mb in size.

PMID- 7584036
TI  - Cloning and characterization of the ribosomal protein genes in the spc operon of
      a prokaryotic endosymbiont of the pea aphid, Acyrthosiphon kondoi.
AB  - To correlate a prokaryotic endosymbiont in the pea aphid, Acyrthosiphon kondoi,
      with the endosymbionts in related aphid species as well as with free-living
      bacteria and subcellular organelles, and to study the mode of its gene expression
      within aphid cells, we have cloned and characterized the genes encoding ribosomal
      proteins S3, L16, L29, S17, L14, L24, L5, S14, S8, L6, L18, S5, L30, L15 and
      secretion protein Y (Sec Y) from the S10 and spc ribosomal protein gene operons
      of this endosymbiont. The organization of these genes is identical to that in
      Escherichia coli, and their nucleotide sequences are highly similar (87%
      identity) to the corresponding E. coli genes. They are much less similar to the
      corresponding chloroplast and mitochondrial genes. The guanine plus cytosine G+C
      content of the genes of the A. kondoi endosymbiont is much higher than those of
      the endosymbionts in related aphid species reported so far. It appears either
      that the A. kondoi endosymbiont is derived from an ancestral bacterium different
      from those in other aphids or that its G+C content increased in a relatively
      short time after the evolutionary divergence of its host.

PMID- 7584038
TI  - The nature of the nucleotide at the 5' side of the tRNA Su9 anticodon affects UGA
      suppression in Escherichia coli.
AB  - In Escherichia coli a UGA codon can be efficiently suppressed by a suppressor
      tRNA(Trp) called Su9. Here, we show that the level of UGA suppression is
      determined by the nature of the nucleotide at the 5' side of the anticodon of the
      suppressor (position 33). UGA suppression occurs when a pyrimidine residue is
      located in position 33 of the tRNA, and suppression is more efficient with a U
      than with a C in this position. On the other hand, when a purine residue is
      located at this position UGA suppression is extremely low. These results show
      that in the case of tRNA Su9, the UGA codon context effect does not require base
      pairing between the nucleotide at the 3' side of the codon and the 5' side of the
      anticodon.

PMID- 7584039
TI  - Restriction enzyme-resistant high molecular weight telomeric DNA fragments in
      tobacco.
AB  - Restriction endonuclease-resistant high-molecular-weight (HMW) DNA fragments were
      isolated from nuclear DNA fragments in tobacco. The size of the fragments
      produced by EcoRI, HindIII, AfaI, and HaeIII ranged from 20 kb to over 166 kb.
      The kinetics of digestion by Bal31 nuclease showed that most of the HMW fragments
      are chromosome ends. The consensus sequence for tobacco telomere repeats was
      determined to be CCCTAAA by genomic sequencing using the HMW fragments and by
      sequencing after cloning. Besides the telomere sequence, 9 tandem repeats of a 45
      bp sequence were identified, in which a 35-bp unit sequence
      (AGTCAGCATTAGGGTTTTAAACCCTAAACTGAACT) formed a stem structure. The front of the
      stem is composed of a palindrome of the telomere repeats. This highly conserved
      unit is surrounded by less conserved internal sequences that are around 10-11 bp
      in size and contain a TTTT stretch. The internal sequences resemble the 10-11 bp
      consensus for the scaffold attachment regions found in yeast and drosophila. The
      characteristic 45-bp sequence was abundant on the ends of chromosomes. The
      shortest distance between the repeats containing telomeric stem and the telomere
      was less than 20 kb. This architecture of the tobacco chromosome end region
      resembles the end region of yeast chromosomes in which autonomous replication
      sequences are present frequently.

PMID- 7584040
TI  - Determination of RAPD markers in rice and their conversion into sequence tagged
      sites (STSs) and STS-specific primers.
AB  - We produced 102 randomly amplified polymorphic DNA (RAPD) markers mapped on all
      12 chromosomes of rice using DNAs of cultivars Nipponbare (japonica) and Kasalath
      (indica) and of F2 population generated by a single cross of these parents. Sixty
      random primers 10 nucleotides long were used both singly and in random pairs and
      about 1,400 primer-pairs were tested. Using both agarose gel and polyacrylamide
      gel electrophoresis enabled us to detect polymorphisms appearing in the range
      from < 100 bp to 2 kb. The loci of the RAPD markers were determined onto the
      framework of our RFLP linkage map and some of these markers were mapped to
      regions with few markers. Out of the 102 RAPD markers, 20 STSs (sequence-tagged
      sites) and STS-specific primer pairs were determined by cloning, identifying and
      sequencing of the mapped polymorphic fragments.

PMID- 7584041
TI  - Chromosomal assignment of short cDNA sequences by PCR using overlapping and
      tailed short primers.
AB  - Overlapping primers and tailed short primers are effective agents for mapping
      very short cDNA sequences. By using such primers, human cDNAs as short as 32
      nucleotides in length can produce PCR bands. Using these and other primers of
      ordinary size, 44 cDNAs were assigned to chromosomes, of which 24 were assigned
      to single chromosomes, and 2 were assigned to two chromosomes and two were
      assigned to three chromosomes, respectively. Among the 24 cDNAs, all of which
      matched GenBank entries, 6 cDNAs were observed to map to the same chromosomes as
      reported previously.

PMID- 7584042
TI  - Evolution of the replication regions of IncI alpha and IncFII plasmids by
      exchanging their replication control systems.
AB  - The basic replicons of bacterial plasmids consist of two sets of genetic systems,
      the replication-structural system and the replication control system. Comparison
      of nucleotide sequences suggested that the basic replicons of plasmids P307
      (IncFI) and pMU2200 (IncZ) were generated by reciprocal recombination between
      ancestors of R100 (IncFII) and ColIb-P9 (IncI alpha), or vice versa. The plasmids
      of each pair, P307/pMU2200 and R100/ColIb-P9, are structurally unrelated to each
      other. Based on this information, we constructed in vitro and analyzed P307-like
      chimeric replicons from ColIb-P9 and R100. When the replication-structural region
      of ColIb-P9 was combined with the whole replication control region of R100, the
      resultant replicon replicated stably as R100 did. These results revealed that the
      basic replicons of the plasmids diverged by exchanging their replication control
      systems. Thus, we propose that the replication control systems of plasmids, in
      some cases, evolved independently of their structural systems, although these two
      systems work together to maintain the replication functions. We also showed that
      the reciprocal recombination was specified by the unique secondary structures of
      RNA involved in the control of expression of the genes encoding the replication
      initiator proteins.

PMID- 7584043
TI  - Organ-specific and auxin-inducible expression of two tobacco par A-related genes
      in transgenic plants.
AB  - We have isolated four genomic DNA clones that contain the transcription
      initiation site of the parA gene(s) from a tobacco genomic library by
      hybridization with the 5' segment of the parA cDNA previously isolated. They were
      classified into two types on the basis of their nucleotide sequences. Southern
      blot analysis indicated that two types of clones were respectively derived from
      the two parental species of tobacco, Nicotiana tomentosiformis and Nicotiana
      sylvestris. The genes corresponding to these clones were designated as parAt and
      parAs, respectively, and the parA cDNA clone was shown to code for mRNA from
      parAt on the basis of its nucleotide sequence. The 5' regions about 400
      nucleotides upstream from the transcription initiation sites of the parAt and
      parAs genomic clones were highly homologous to one another, but regions further
      upstream showed no significant similarity. The coding sequence of the GUS (beta
      glucuronidase) reporter gene was linked to the 5'-upstream regions of parAt and
      parAs, and the sites of expression of these fusion genes were examined in
      transgenic tobacco plants. In the absence of auxins, both fusion genes were
      expressed in capsules at a late stage of seed development, mature seeds, a root
      apex and a root-hair zone whereas no significant expression was seen in other
      organs. Their expression was enhanced by 2,4-dichlorophenoxyacetic acid in most
      of the organs of tobacco. The results show that expression of these genes is
      regulated by both organ-specific and auxin-inducible mechanisms.

PMID- 7584045
TI  - DNA sequencing directly from a mixture using terminal-base-selective primers.
AB  - DNA cloning is often used to select and amplify one DNA species from a mixture.
      However, the cloning process is complex and labor-intensive. We have developed a
      new two-step method for DNA sequencing directly from a mixture. The first is the
      introduction of a known oligonucleotide (common part) into the terminus of
      unknown DNA by ligation. The second is selective DNA sequencing using primers
      with two additional nucleotides at the 3' terminus in addition to the common part
      (terminal-base-selective primers). The primers work only for templates on which
      the primers perfectly hybridized. This method was found to be effective for the
      HindIII digestion products of lambda phage.

PMID- 7584044
TI  - Prediction of the coding sequences of unidentified human genes. II. The coding
      sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones
      from human cell line KG-1.
AB  - By applying the protocol previously established, we isolated and sequenced full
      length cDNA clones longer than 2 kb from cDNA library of human immature myeloid
      cell line KG-1, and the coding sequences of 40 new genes were predicted. A
      computer search of the sequences indicated that 29 genes contained sequences with
      similarities to reported genes in the GenBank/EMBL databases. Significant
      transmembrane domains were identified in 9 genes, 5 of which harbored multiple
      hydrophobic regions. Protein motifs that matched those in the PROSITE motif
      database were identified in 13 genes. In terms of sequence similarities and
      protein motifs, 5 genes were related to transcriptional factors. Repetitive
      sequences were found in the 3'-untranslated region of 8 genes. Northern
      hybridization demonstrated that the expression of 9 genes was tissue-specific,
      while the remaining 31 genes were expressed ubiquitously. It was also noted that
      17 genes yielded different sizes of bands possibly due to either alternative
      splicing or alternative initiation. The chromosomal location of these genes has
      been determined.

PMID- 7584046
TI  - Direct determination of NotI cleavage sites in the genomic DNA of adult mouse
      kidney and human trophoblast using whole-range restriction landmark genomic
      scanning.
AB  - Restriction landmark genomic scanning (RLGS) is a method for visualizing
      restriction landmarks, employing direct labeling of restriction sites of genomic
      DNA and high-resolution two-dimensional electrophoresis. We determined the
      conditions for both the first and second dimensions of RLGS that define all of
      the restriction fragments which carry the NotI landmark. Using this system, we
      determined the number of cleavable NotI sites of genomic DNA from the mouse
      kidney (C57BL/6) and from the human placenta. The mouse and human genomes were
      cleaved at 2,380 +/- 80 sites (4,760 +/- 160 spots) and 3,240 +/- 110 sites
      (6,480 +/- 220 spots), respectively with NotI.

PMID- 7584047
TI  - A PCR-mediated method for cloning spot DNA on restriction landmark genomic
      scanning (RLGS) gel.
AB  - A PCR-mediated direct cloning for target spot DNA from RLGS gel has been
      established. The method consists of PCR amplification of adaptor-ligated spot DNA
      fragments without excluding similar-sized DNA fragments co-localized on RLGS gel,
      and following selective ligation with the NotI-dT vector. Applying this method,
      we have successfully cloned several DNA fragments derived from target spots whose
      intensities change developmentally due to DNA methylation in the telencephalon of
      C3H/HeN mice. Since only a few micrograms of total DNA is sufficient for our spot
      cloning, our method may be highly useful when the total DNA sample prepared for
      cloning is limited.

PMID- 7584048
TI  - Prediction of the coding sequences of unidentified human genes. II. The coding
      sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones
      from human cell line KG-1 (supplement).

PMID- 7584049
TI  - Cloning and sequencing of a 36-kb region of the Bacillus subtilis genome between
      the gnt and iol operons.
AB  - Within the framework of an international project for the sequencing of the entire
      Bacillus subtilis genome, a 36-kb chromosome segment, which covers the region
      between the gnt and iol operons, has been cloned and sequenced. This region
      (36447 bp) contains 33 complete open reading frames (ORFs; genes) including the
      four gnt genes and one partial gene. A homology search for the products of the 33
      complete ORFs revealed significant homology to known proteins in 16 of them such
      as tetracycline resistance protein (Clostridium perfringens), asparagine
      synthetase (Arabidopsis thaliana), aldehyde dehydrogenase (Pseudomonas
      oleovorans), 2,5-dichloro-2,5-cyclohexadiene-1, 4-diol dehydrogenase (P.
      paucimobilis), heat shock protein HtpG (Escherichia coli), galactose-proton
      symporter (E. coli), auxin-induced protein (common tobacco), glucitol operon
      repressor (E. coli) and methylmalonate-semialdehyde dehydrogenase (P.
      aeruginosa). Unlike the regions we sequenced so far, this region contained two
      short sequence multiplications: one was a tandem sequence duplication (409 and
      410 bp), and the other a triplication consisting of two highly conserved 118-bp
      tandem sequences preceded by a less conserved similar sequence (129 bp). The
      reasons for the presence of these sequence multiplications in the gnt to iol
      region were deduced.

PMID- 7584050
TI  - Genes encoding the group I intron-containing tRNA(Leu) and subunit L of NADH
      dehydrogenase from the cyanobacterium Synechococcus PCC 6301.
AB  - A part of the tRNA(Leu)(UAA) gene containing a 240-nucleotide group I intron was
      amplified by PCR from cyanobacterium Synechococcus PCC 6301 genomic DNA. The pre
      tRNA synthesized from the cloned PCR product was efficiently self-spliced in
      vitro under physiological conditions. The gene encoding the tRNA(Leu)(UAA), trnL
      UAA, was isolated from a Synechococcus PCC 6301 genomic library and the
      nucleotide sequence of a 2,167-bp portion was determined. The trnL-UAA consists
      of a 34-bp 5' exon, a 240-bp group I intron and a 50-bp 3' exon. In addition,
      three open reading frames (ORF1, ORF2 and ORF3) were found in the 5' and 3'
      flanking regions of trnL-UAA. The predicted protein sequence of ORF3, which is
      located 74-bp upstream from trnL-UAA on the opposite strand, shows 66.2% amino
      acid identity to that of the Synechocystis PCC 6803 gene encoding subunit L of
      NADH dehydrogenase (ndhL).

PMID- 7584054
TI  - Gene therapy--heralding a new era.

PMID- 7584053
TI  - srb: a Bacillus subtilis gene encoding a homologue of the alpha-subunit of the
      mammalian signal recognition particle receptor.
AB  - We cloned a Bacillus subtilis gene (srb) encoding a homologue of the mammalian
      signal recognition particle receptor alpha-subunit (SR alpha). The gene is 987 bp
      in length and encodes a 329-amino acid protein. The deduced amino acid sequence
      of the protein shared 26.6, 36.2 and 49.7% identity with those of mammalian SR
      alpha, archaebacterial DP alpha and Escherichia coli FtsY, respectively. The
      protein contains three conserved GTP-binding elements like the other three SRP
      receptor proteins, though the N-terminal portion of the putative B. subtilis
      protein was shorter than the others. Secondary structure prediction showed than
      an amphipathic alpha-helix is positioned in the N-terminal region. A defect in
      srb inhibited cell growth and protein translocation.

PMID- 7584051
TI  - Isoform diversity and tandem duplication of the glycoprotein A gene in ferret
      Pneumocystis carinii.
AB  - Two ferret P. carinii gpA cDNA clones were identified that reacted identically
      with a panel of anti-gpA monoclonal antibodies, although their nucleotide
      sequences were 22% divergent. Each clone hybridized to a single mRNA species of
      3,600 nucleotides only in P. carinii-infected lung mRNA, but RT-PCR analysis
      demonstrated that these cDNA clones were derived from two distinct gpA mRNA
      transcripts. Further PCR analysis demonstrated that the ferret P. carinii genome
      contains at least two gpA genes lying in tandem on a single chromosome separated
      by a 329-bp intergenic region. Based on the terminal gene sequences of this
      tandem repeat and the cDNA clones, a composite full-length ferret P. carinii gpA
      coding sequence was constructed. The intergenic region immediately downstream of
      the stop codon of the first gpA gene contains three putative polyadenylation
      signals, and constitutes the 3' untranslated region (UTR) of the gpA mRNA. Primer
      extension of the gpA mRNA resulted in products extending 74 and 244 nucleotides
      into the 5' UTR. However, the intergenic region lying greater than 25 nucleotides
      upstream of the first methionine of the second gpA gene was found to be absent
      from the 5' UTR.

PMID- 7584052
TI  - Structural analysis of a recA-like gene in the genome of Arabidopsis thaliana.
AB  - A recA-like gene was identified in the genome of Arabidopsis thaliana by means of
      PCR using primers designed on the basis of previously reported amino acid
      sequences of eukaryotic RecA-like proteins. The structure of the gene, termed
      ArLIM15, was investigated by comparing the primary structure of the genomic DNA
      with that of the corresponding cDNA. The open reading frame, which was split into
      15 exons, was established to have the capacity for encoding a 37.3-kDa
      polypeptide. The amino acid sequence of the putative product of ArLIM15 showed a
      high degree of similarity to that of LIM15 in the monocotyledonous plant Lilium,
      including a 93% identity, and to those of other recA-like genes in yeasts and
      vertebrates with identities of 69-71%. Phylogenetic analysis indicated ArLIM15 to
      be much closer to meiosis-specific LIM15 and DMC1 in Saccharomyces cerevisiae
      than to RAD51 in S. cerevisiae and its homologues on an evolutionary scale.

PMID- 7584056
TI  - Rapid protection against human immunodeficiency virus type 1 (HIV-1) replication
      mediated by high efficiency non-retroviral delivery of genes interfering with HIV
      1 tat and gag.
AB  - Efficient transduction of inhibitory genes is a critical requirement in the
      development of a gene therapy strategy against human immunodeficiency virus type
      1 (HIV-1). Commonly used systems based on retrovirus-mediated gene delivery are
      characterized by low efficiency gene transfer into the target cell. Genes were
      transduced in the absence of cell selection into 60-90% of human CD4+ cells by
      using a novel technique that allows high efficiency gene transfer mediated by
      adenoviruses coupled with DNA-polylysine complexes. Protection of these cells
      against HIV-1 acute infection was evaluated by transducing them with three
      different inhibitory genes which interfere with HIV-1 replication at separate
      levels (polymeric Tat activation response element [TAR] decoy, dominant-negative
      mutant of the gag gene and antisense sequences of the gag gene) and subsequent
      challenging with HIV-1. The polymeric TAR decoy inhibited HIV-1 replication over
      95%. Both the dominant-negative mutant and the antisense sequence of the gag gene
      were less potent inhibitors than the polymeric-TAR decoy. Combinations of either
      polymeric-TAR with dominant-negative mutant or antisense of the gag gene
      synergistically enhanced the inhibitory effects of the single genes. These data
      suggest that the combination of a highly efficient transduction technique with
      effective HIV-1 inhibitory genes confers rapid protection against HIV-1 acute
      infection in vitro.

PMID- 7584057
TI  - Regulated expression of a dominant negative form of Rev improves resistance to
      HIV replication in T cells.
AB  - Infection by the human immunodeficiency virus (HIV) has remained refractory to
      treatment, and molecular genetic interventions have been developed for the
      treatment of the acquired immunodeficiency syndrome (AIDS). Previous studies have
      focused on the development of gene products which inhibit productive HIV
      replication, including transdominant proteins, RNA decoys and ribozymes. In this
      report, we show that appropriate expression vectors which optimize production and
      regulated synthesis of a transdominant mutant form of Rev improve its antiviral
      effect. The combination of a strong constitutive enhancer, a Tat activation
      response (TAR) regulatory element and transdominant Rev take advantage of three
      aspects of early viral gene expression to confer increased resistance to HIV
      replication. This vector may be useful, alone or in combination with other
      antiviral genes, to provide gene therapy for AIDS.

PMID- 7584058
TI  - Intracellular immunization of human T cells with a hairpin ribozyme against human
      immunodeficiency virus type 1.
AB  - T-cell lines (Jurkat and Molt-4) were transduced with retroviral vectors
      containing a hairpin ribozyme that targets a conserved sequence in the 5'
      transcribed leader sequence of human immunodeficiency virus (HIV) type 1. Stable
      cell lines were generated which constitutively and persistently expressed the
      ribozyme gene driven by either the Moloney retroviral long terminal repeat (LTR)
      or an internal human tRNA(val) promoter. There was no apparent deleterious effect
      of long-term ribozyme expression on cell proliferation or viability. Cells
      expressing ribozyme were resistant to challenge from diverse strains of HIV,
      including an uncloned clinical isolate. No reverse transcriptase activity or
      virus infectivity was detectable in the culture supernatants of Jurkat cells
      expressing the ribozyme driven by the tRNA(val) promoter up to 35 days after
      challenge with HIV-1/HXB2. Expression of the ribozyme also significantly
      decreased (by approximately 50- to 100-fold) the efficiency of incoming virus to
      synthesize viral DNA. These and previously reported results indicate that
      transfer and expression of the ribozyme gene interfere with both early and late
      events in the HIV replication cycle and confer long-term resistance to HIV-1
      infection.

PMID- 7584055
TI  - Progress towards gene therapy for HIV infection.
AB  - The retroviral life cycle and genetic plasticity of human immunodeficiency virus
      1 (HIV-1) present unprecedented therapeutic challenges. Twelve years into the HIV
      epidemic, satisfactory treatment remains elusive. Our current understanding of
      AIDS pathogenesis calls for early intervention with antiviral agents. Although
      still in its infancy, human gene therapy holds considerable potential for the
      long-term treatment of genetic disorders, cancer and chronic infectious diseases.
      Gene therapy for HIV infection is receiving particularly intensive study:
      approaches that are in development include both immunotherapy (e.g. therapeutic
      vaccines and adoptive transfer of CD8+ T-cell clones) and direct antiviral
      therapy (intracellular immunization). The latter strategies include transdominant
      modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes and
      modifications of cellular proteins (e.g. intracellular antibodies, soluble CD4).
      Several of these strategies are now entering clinical trials. While significant
      conceptual and technical hurdles remain to be overcome before the promise of gene
      therapy for HIV infection can be fully realized, progress in this field is likely
      to be rapid and to contribute to the broader applicability of human gene therapy
      to the treatment of other disorders.

PMID- 7584059
TI  - Strategy for achieving selective killing of carcinomas.
AB  - Carcinomas are malignancies derived from epithelial cells that frequently respond
      poorly to conventional chemotherapy. Selective expression or transduction of
      toxin genes to carcinomas, i.e. molecular chemotherapy, may offer important
      advantages over conventional chemotherapy. As one approach to developing a means
      of selectively expressing toxin genes, the transcriptional regulatory sequences
      of a gene expressed in multiple carcinomas were used to direct expression of the
      herpes simplex virus thymidine kinase (HSVtk) coding sequences. The secretory
      leukoprotease inhibitor (SLPI) gene was found to be expressed in lung, breast,
      oropharyngeal, bladder, endometrial, ovarian and colorectal carcinomas. The
      tissue-specific transcriptional regulatory sequences were isolated and used to
      construct a chimeric gene in which the SLPI sequences directed HSVtk expression.
      SLPI-expressing carcinomas were reduced in number by transduction of the SLPI
      directed toxin plasmid plus ganciclovir, but the same treatment had no effect on
      a cell line that did not express SLPI. These results suggest that SLPI-directed
      therapeutic genes could be used for directing toxicity to carcinoma tissues,
      especially if combined with other targeting strategies.

PMID- 7584060
TI  - Efficient catheter-mediated gene transfer into the heart using replication
      defective adenovirus.
AB  - The ability to express recombinant genes in the coronary vasculature and the
      myocardium holds promise for the treatment of a number of acquired and inherited
      cardiovascular diseases. Previous in vivo gene transfer approaches in the heart
      have been limited by relatively low efficiencies of gene transduction. In this
      report, we demonstrate that catheter-mediated infusion of replication-defective
      adenovirus into the coronary arterial circulation in vivo represents a novel and
      efficient method for the induction of recombinant gene expression in both the
      coronary arteries and the myocardium. A single intracoronary infusion of 2 x
      10(9) - 1 x 10(10) p.f.u. of adenovirus resulted in high level recombinant gene
      expression in both the coronary arteries and surrounding myocardium of adult
      rabbits for at least 2 weeks. No inflammatory response or myocardial necrosis was
      observed following the adenovirus infusions. The polymerase chain reaction (PCR)
      was used to assess the tissue distribution of infection following intracoronary
      infusion of adenovirus. Adenovirus DNA was detected by PCR in the livers,
      kidneys, lungs, brains and testes of animals 5 days after virus infusion.
      Percutaneous transluminal gene transfer (PTGT) into the heart by intracoronary
      infusion of replication-defective adenovirus represents a relatively non-invasive
      and efficient method of inducing recombinant gene expression both in the coronary
      arterial wall and in the surrounding myocardium.

PMID- 7584061
TI  - A powerful method for in vitro selection of normal versus cystic fibrosis airway
      epithelial cells.
AB  - In preparation for a gene therapy approach to cystic fibrosis involving the
      precise repair of mutations on the CF gene by homologous recombination, we
      developed a method that would allow for selection of the CFTR+ cells originated
      in gene targeting experiments on CFTR- cells in vitro. The method is based on the
      differential sensitivity we observed between CFTR+ and CFTR- cells to agents
      stimulating cyclic adenosine monophosphate (cAMP). Controlled treatment with
      epinephrine or forskolin allows for selectively killing CFTR- cells. The
      efficiency of the selection method would make it suitable for rescuing the few
      corrected cells originated from rare homologous recombination events.

PMID- 7584062
TI  - Suppression of intra-articular responses to interleukin-1 by transfer of the
      interleukin-1 receptor antagonist gene to synovium.
AB  - We have developed an ex vivo method for delivering genes to the synovial lining
      of joints and expressing them intra-articularly. The present studies were
      designed to determine whether transfer of a human interleukin-1 receptor
      antagonist protein (IRAP) gene by this method was able to antagonize the intra
      articular actions of interleukin-1. Intra-articular injections of human
      recombinant interleukin-1 beta (hrIL-1 beta) into the knees of control rabbits
      provoked a marked leukocytic infiltrate into the joint space, severe synovial
      thickening and hypercellularity, and loss of proteoglycans from articular
      cartilage. Genetically modified knees contained several nanograms of human IRAP
      and inhibited each of these effects of IL-1 beta. These data demonstrate for the
      first time that delivery of an appropriate gene to joints can prevent intra
      articular pathology. Such findings permit cautious optimism about the eventual
      development of a gene treatment for arthritis and other disorders of the joint.

PMID- 7584064
TI  - Insertion of a pathogenic mutation into a yeast artificial chromosome containing
      the human amyloid precursor protein gene.
AB  - The genetic modelling of human disease would be considerably facilitated if
      pathogenic mutations could be inserted into transgenes which were then expressed
      in an appropriate manner. Yeast artificial chromosomes (YACs), when used as
      transgenes appear to direct expression with the correct temporal and spatial
      distribution. Here we demonstrate that it is comparatively straightforward to
      introduce pathogenic mutations into such YACs by the use of the 'pop-in, pop-out'
      procedure, by inserting an Alzheimer-causing mutation (APP717Val-->lle) into an
      APP-containing YAC which has previously been used as a transgene. The
      significance of these procedures for the modelling of human disease is discussed.

PMID- 7584063
TI  - Mammalian artificial chromosomes: a new tool for gene therapy.
AB  - Effective therapy by in vivo delivery of DNA requires efficient delivery, long
      term maintenance of the DNA that is delivered and physiological levels of
      expression of the therapeutic gene. Full levels of physiologically controlled
      expression can be obtained after transfer of intact genes on fragments of DNA
      hundreds of kilobases in size, as has been demonstrated by the transfer of yeast
      artificial chromosomes into transgenic mice. Long-term maintenance of input DNA
      could be achieved if the DNA carried replication origins, a centromere and
      telomeres to allow maintenance and segregation in mammalian cells, and there has
      been recent progress towards cloning these elements. These features could be
      combined as a mammalian artificial chromosome which would confer full levels of
      controlled expression as well as being maintained in any cell into which it was
      introduced. Methods which would allow delivery of such large fragments of DNA
      include liposomes and receptor-mediated uptake, both of which have been shown to
      work in vivo, making such large constructs potentially applicable for use in gene
      therapy.

PMID- 7584066
TI  - Pharmacological enhancement of in vivo foreign gene expression in muscle.
AB  - Intramuscular injection of naked plasmid DNA provides a means for gene transfer
      and expression in striated muscle. In this study, the effects of treating muscle
      with normal saline, etidocaine, mepivacaine, acetic anhydride, sodium
      bicarbonate, Notechis scutatus venom, cardiotoxin and bupivacaine before plasmid
      DNA injection on foreign gene expression were evaluated. Dose dependence, strain
      and species specificity, the time interval between pharmacological agent and
      plasmid DNA injection, the stability of gene expression and the fate of the
      injected plasmid DNA were studied using reporter gene expression, by histological
      examination and semi-quantitative polymerase chain reaction. Of the various
      agents tested, the best enhancement of foreign gene expression occurred in muscle
      treated with 0.75% bupivacaine five to seven days before plasmid DNA injection.
      Rat and mouse quadriceps muscle treated with 0.75% bupivacaine had levels of
      luciferase activity four- to 40-times greater than non-bupivacaine-treated
      muscle. Also, beta-galactosidase expressing myofibers were observed throughout
      the length of the muscle in samples treated with 0.75% bupivacaine before
      reporter gene injection. Muscle treated with 0.75% bupivacaine fully recovered
      from the degeneration caused by its injection with no long-term effects
      histologically. The heightened level of reporter gene expression persisted in
      0.75% bupivacaine-treated muscle for one month, but decreased to that of non
      bupivacaine-treated muscle by two months after plasmid DNA injection. Enhancement
      of foreign gene expression may be particularly advantageous in vaccination
      protocols employing intramuscular plasmid injection.

PMID- 7584065
TI  - Gene complementation using myoblast transfer into fetal muscle.
AB  - Gene complementation by myoblast transfer into neonatal or adult muscle has been
      proposed as a therapy for primary myopathies as well as to augment non-muscle
      gene products that may be diminished in the adult circulation. This paper
      describes a technique whereby myoblasts have been injected into limb muscles of
      normal and dystrophin-deficient (mdx) fetal mice (during the period of active
      myotube formation and prior to the development of the host's immune competence)
      without significantly interfering with fetal viability or further maturation.
      More mosaic myofibers (myofibers containing both host- and donor-derived
      myonuclei) appear to result from these transfers than have been reported
      following myoblast transfer into neonatal muscle or adult muscle. The small size
      of the fetal hosts' muscles and the lack of well-defined connective tissue septa
      facilitate migration of donor myoblasts into muscle groups distal to the
      injection site. The use of donor myoblasts derived from a tetraploid variant of a
      mouse myogenic cell line (MM14) provides a convenient and permanent cytological
      marker for the recognition of donor myoblasts and donor-derived myonuclei. When
      MM14 myoblasts are injected into mdx fetuses, whose muscles lack dystrophin,
      mosaic myofibers contain sufficient dystrophin to be visualized with routine
      immunohistochemical techniques. The myoblast transfer system, using fetal hosts,
      described in this study will facilitate the evaluation of myoblasts as vectors to
      overcome genetic deficiencies that may be manifested during fetal development.

PMID- 7584067
TI  - In vivo adenovirus-mediated gene transfer into ocular tissues.
AB  - Replication-deficient adenoviruses have been successfully used to transfer
      foreign DNA into a variety of cells including post-mitotic cells, in vivo. In the
      eyes, most of the cells are quiescent or slowly dividing. They constitute the
      obligatory targets of gene transfer for a number of ocular diseases that have
      been elucidated at the molecular level and are potential targets for gene
      therapy. We have therefore analysed the ability of an adenovirus vector to
      transfer in vivo the Escherichia coli lacZ gene into ocular cells of mice.
      Injection of up to 3 x 10(7) p.f.u. into the vitreous body, the anterior chamber
      or the peribulbar space, did not result in any detectable cytopathic effect and
      was associated with endocytosis of viral particles in corneal endothelial,
      photoreceptor, bipolar, ganglionic and oculomotor muscle cells, depending on the
      administration route. At the viral titer used (3 x 10(7) p.f.u.), the expression
      was detected for at least 50 days. These results open new prospects for the
      treatment of some retinal hereditary disorders and acquired corneal or retinal
      alterations due to inflammatory disease.

PMID- 7584068
TI  - Antisense inhibition of acetylcholinesterase gene expression causes transient
      hematopoietic alterations in vivo.
AB  - Hematopoietic acetylcholinesterase (ACHE) gene expression and its implication for
      development were studied by in vivo administration to mice of an antisense
      phosphorothioate oligonucleotide targetted toward ACHE (AS-ACHE). Hematopoietic
      alterations were observed by differential cell counts and ACHE mRNA levels
      determined by quantified RNA polymerase chain reaction (RNA-PCR) and in situ
      hybridization analyses. In control mice, injected with phosphate-buffered saline
      and untreated, ACHE mRNA labeling with ACHE [35S]cRNA was about 10-fold higher on
      megakaryocytes (MK) compared with all other bone marrow cells and increased by 20
      fold during MK development, similar to reports for MK actin mRNA. Drastic
      reductions occurred in the bone marrow lymphocyte and erythroid fractions 12 days
      following intraperitoneal injection of AS-ACHE (5 micrograms/g weight) into
      groups of four mice. RNA-PCR revealed over 1000-fold decreases in ACHE mRNA
      levels in lymph nodes and bone marrow at this time, while actin mRNA levels
      dropped by 10 and 100-fold in lymph nodes and bone marrow of AS-ACHE treated mice
      compared with controls. In view of the developmental increase in MK actin, this
      suggested arrest in MK development as well. By 20 days postinjection, bone marrow
      actin mRNA was fully restored and the sensitive in situ hybridization technique
      revealed that ACHE mRNA levels were also restored and reached levels only 2-3
      fold lower than in controls in all bone marrow cells of AS-ACHE treated mice.
      Moreover, lymphocytes and erythroid cells repopulated to levels 25% above normal,
      and promegakaryocyte and mature MK fractions of the total MK were 3 and 2-fold
      higher, respectively, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584069
TI  - Versatile retroviral vectors for potential use in gene therapy.
AB  - A set of retroviral vectors is described whose capacity for high efficiency
      transduction of functional genes into undifferentiated murine embryonic and
      haematopoietic cells makes them ideally suited for preclinical studies with
      murine models. Multiple unique cloning sites permit insertion of genes into the
      vectors such that no selectable marker exists or either the neomycin
      phosphotransferase (neo) gene, the hygromycin B phosphotransferase (hph) gene or
      the puromycin N-acetyl transferase (pac) gene is included as a dominantly acting
      selectable marker. Because the sequences in the viral gag region shown to improve
      the encapsidation of viral RNA have been modified to prevent viral protein
      synthesis and all env sequences have been removed to eliminate helper virus
      production by homologous recombination with packaging DNA, these vectors might
      prove useful in human gene therapy protocols.

PMID- 7584071
TI  - Skeletal muscle as a target for gene therapy.

PMID- 7584070
TI  - Gene therapy for cystic fibrosis in humans by liposome-mediated DNA transfer: the
      production of resources and the regulatory process.
AB  - The number of clinical trials using gene transfer technology, either active or
      under discussion, is increasing rapidly. However, little information is available
      describing the regulatory procedures or safety specifications that must be
      considered before initiation of such trials in Europe. We describe the procedure
      used by our group to produce resources for the first stage of a phase I trial of
      liposome-mediated gene therapy for cystic fibrosis. The current lack of written
      and co-ordinated guidance from the numerous interested regulatory agencies within
      the UK and Europe makes determination of the appropriate safety specifications
      and procedures for these novel trials difficult, as does the fact that some new
      agencies (such as the Genetic Therapy Advisory Committee in the UK) and some
      which are unfamiliar with clinical trials (such as the Department of the
      Environment) are involved as well as the Medicines Control Agency. In addition,
      we estimate that the realistic cost of these trials, which in many cases will
      have to be covered from research budgets provided by government agencies or
      medical charities, could lead to delays in the clinical application of this
      important new therapeutic strategy.

PMID- 7584072
TI  - The role of IL-2 in gene therapy.
AB  - Interleukin-2 (IL-2) is a growth factor for T-cells which enhances both non
      specific immune responses such as natural killer (NK) and lymphokine-activated
      killer (LAK) cells as well as MHC-restricted cytotoxic T-cell responses. Early
      studies using IL-2 to treat a number of advanced cancers suggested that it may be
      active against malignant melanoma and renal cell carcinoma. However, responses
      were at the expense of considerable morbidity and mortality. Those, and
      subsequent studies, which aimed at increasing the efficacy and reducing the
      toxicity of IL-2-based treatments, are briefly reviewed and the current situation
      in which IL-2 is being used more frequently, in low dose subcutaneously
      administered regimens (often in combination with other agents such as alpha
      interferon) assessed. The ultimate application of IL-2 against human cancer may
      be when it is secreted either by tumour-infiltrating lymphocytes or the tumour
      cells themselves. A number of studies using this approach are about to commence
      or have already started. Tumour cells transduced with IL-2 could effectively act
      as a therapeutic vaccine against low volume disease.

PMID- 7584073
TI  - Gene transfer technologies for the gene therapy of cancer.
AB  - Gene therapy for cancer relies upon the delivery of a therapeutic gene to a
      target cell population which may comprise either the tumour cells themselves or
      specific host effector cells with anti-tumour activity. In addition, gene
      delivery may be targeted directly to the tumour cells in vivo or towards cells
      explanted from the patient. The precise requirements of the delivery system
      depend upon the specific therapeutic strategy being used. In each case, however,
      delivery must be accurate, efficient and must result in correctly regulated
      expression of the gene in only the desired cell type. Equally important, the
      delivery system must be safe for both the patient and the community as a whole.
      Here, we summarize the types of gene therapy which have been proposed for the
      treatment of cancer and review how currently available delivery systems are
      suited to each of these individual strategies.

PMID- 7584076
TI  - Liver-directed gene therapy: prospects and problems.
AB  - The development of strategies for gene therapy in the liver is a challenging task
      because this organ is particularly involved in the manifestation of numerous
      genetic diseases as well as in malignant and infectious diseases. Most of the
      available techniques for gene transfer were already applied to hepatocytes ex
      vivo. Attempts to retransplant retrovirally transduced hepatocytes back to
      patients have shown the limits of the ex vivo approach. The obvious alternative
      would be the development of suitable techniques for gene transfer in vivo. Both
      viral and non-viral delivery systems were tested in animal models with limited
      success. This article summarizes the state of the art of the available techniques
      and vectors and discusses the essential future developments.

PMID- 7584075
TI  - Genetic approaches to cancer therapy.

PMID- 7584074
TI  - Primary myoblast-mediated gene transfer: persistent expression of human factor IX
      in mice.
AB  - Primary myoblast-mediated gene transfer was tested for its ability to mediate a
      persistent expression of recombinant human factor IX in SCID mice. Mouse primary
      myoblasts were transduced with factor IX retroviral vectors, LIXSN, which uses
      the retroviral long-terminal repeats as the promoter, or dLMMBAIX, which uses
      muscle creatine kinase enhancer and beta-actin promoter to drive factor IX
      transcription. In vitro, myoblasts transduced with either LIXSN or dLMMBAIX
      expressed recombinant human factor IX with full biological activity. Upon
      implantation of transduced myoblasts into skeletal muscles of SCID mice, a
      sustained systemic expression of factor IX at a level of 10-30 ng/ml plasma was
      achieved. This was further supported by the presence of recombinant factor IX
      protein and mRNA in muscle tissues after 5 months of myoblast implantation.
      Intramuscular implantation of the transduced myoblasts resulted in a gene
      transfer which was confined locally to the region of injection, with no
      dissemination to other organs and tissues including testis. Additionally, basic
      fibroblast growth factor co-injected with primary myoblasts significantly
      improved the expression level of recombinant factor IX in vivo. These results
      demonstrate that primary myoblast-mediated gene therapy for hemophilia B is
      feasible and safe, and can be optimized by using cytokines or other conditions
      which augment myoblast survival and fusion with myofibers.

PMID- 7584077
TI  - Targeted integration of transfected and infected adeno-associated virus vectors
      containing the neomycin resistance gene.
AB  - Human adeno-associated virus (AAV) integrates specifically into a site (AAVS1) on
      chromosome 19q13.3-qter. We report that both transfected and infected AAV-vectors
      will target a foreign gene preferentially to AAVS1. Of 11 infected cell lines
      studied, nine (82%) showed integration of the neomycin resistance marker into
      AAVS1, which confirms the findings of previous investigations. We also show site
      specific integration (nine out of 12 cell lines, 75%) following transfection of
      an AAV vector containing the neomycin gene. The ability of transfected AAV
      sequences to preferentially target and express selectable genes at a known site
      in the human genome extends the potential use of AAV as a vector in gene therapy.

PMID- 7584078
TI  - Gene therapy for cancer using tumour-specific prodrug activation.
AB  - Current treatments for metastatic malignant disease are often ineffective. One of
      the most promising of the selective genetic strategies against cancer is VDEPT
      (virally directed enzyme prodrug therapy). This uses a viral vector to carry a
      prodrug-activating enzyme gene into both tumour and normal cells. By linking the
      foreign gene downstream of tumour-specific transcription units, tumour-specific
      expression of the foreign enzyme gene can be achieved. We have developed a
      genetic therapy strategy using VDEPT against cancers that overexpress the
      oncogene ERBB2. This occurs in approximately one-third of breast and pancreatic
      tumours (and in a smaller proportion of other tumours) and involves
      transcriptional up-regulation of the ERBB2 gene with or without gene
      amplification. We have constructed a chimeric minigene consisting of the proximal
      ERBB2 promoter linked to the gene encoding cytosine deaminase, an enzyme that can
      deaminate the prodrug 5-fluorocytosine (5-FC) to form cytotoxic 5-fluorouracil (5
      FU). We have constructed a double-copy recombinant retrovirus to deliver the
      enzyme gene under the control of the ERBB2 promoter into a panel of ERBB2
      expression-positive (ERBB2+) and -negative (ERBB2-) pancreatic and breast cell
      lines. Cytosine deaminase activity was high in ERBB2+ transduced cells but was
      not detected in ERBB2- transduced cells. Significant cell death was observed in
      ERBB2+ transduced cells treated with 5-FC whereas ERBB2- cells were not affected.
      Hence we present a novel gene therapy strategy that is potentially tumour
      specific and could be used against a range of tumour types that overexpress the
      ERBB2 oncogene.

PMID- 7584079
TI  - Transduction of CD34+ enriched cord blood and Gaucher bone marrow cells by a
      retroviral vector carrying the glucocerebrosidase gene.
AB  - One promising strategy for gene therapy of Gaucher disease involves ex vivo
      retroviral transduction of autologous hematopoietic stem cells. Studies in small
      animals have demonstrated that this approach provides a life-long supply of the
      glucocerebrosidase (GC) enzyme. Human application has developed to the stage of a
      clinical trial. In this study, we describe development of a high titer
      amphotropic producer line for the vector, MFG-GC, and explore transduction of
      CD34+ cells from various human sources. Higher than three times the normal levels
      of glucocerebrosidase activity in non-transduced cells were achieved following
      transduction of CD34+ cells obtained from bone marrow or cord blood from normal
      donors. The improvement in enzyme activity in Gaucher marrow was about 40-fold
      above deficient levels. We examined the timing and stepwise effect of multiple
      rounds of infection and evaluated post-infection expansion of cells in two
      different cytokine mixtures. Transduction efficiency was determined using
      immunocytochemistry and Southern blot hybridization.

PMID- 7584080
TI  - Folate receptor mediated DNA delivery into tumor cells: potosomal disruption
      results in enhanced gene expression.
AB  - We have used a particular folate receptor, which is overexpressed in tumor cells,
      for targeted DNA delivery into these cell types. This folate receptor
      internalizes folate through caveolae by a process named potocytosis, which is
      distinct from endocytosis, through clathrin-coated pits. When folate conjugated
      to poly-L-lysine was used to deliver the E. coli beta-galactosidase gene into
      tumor cells overexpressing the folate receptor, only low levels of beta
      galactosidase activity were detectable. When a replication-defective adenovirus
      was coincubated with the DNA/folate complexes, 20 to 30% of the cells stained
      blue with X-gal and a 1000-fold increase of beta-galactosidase activity was
      observed. Thus, for high efficient DNA delivery and gene expression via the
      caveolae system, a potosomal disruption agent is needed. Furthermore, folate
      mediated DNA delivery is restricted to tumor cells that highly overexpress the
      folate receptor, which will permit future development of tumor cell-specific
      delivery of toxic genes for cancer gene therapy.

PMID- 7584081
TI  - Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of
      repeated in vivo vector administration to the lung.
AB  - Adenoviral vectors have an important role as in vivo gene delivery vehicles in
      developing human gene therapy for the fatal pulmonary component of cystic
      fibrosis. In this study we evaluated the immune responses to wild-type adenovirus
      and replication-deficient, first generation adenoviral (Av1) vectors in the
      cotton rat (Sigmodon hispidus) and then quantitatively evaluated the efficiency
      of gene delivery and expression of single and repeated in vivo administration of
      Av1 vectors to the respiratory tract. Av1 vector reporter gene expression was
      quantitatively evaluated by employing a luciferase expression vector (Av1Luc1)
      and measuring luciferase activity in whole lung tissue homogenates by routine
      luminometry. Gene transfer and expression in naive animals (e.g. first Av1 vector
      dose) was efficient. A repeat dose also resulted in successful gene transfer and
      expression, although at a significantly reduced level (p < 0.01) compared with
      naive animals. This reduction inversely correlated with serum human adenovirus
      neutralizing antibody (HANA) titers. Importantly, increasing doses of Av1Cf2, an
      Av1 vector expressing the human CFTR cDNA, resulted in a graded HANA response
      consistent with a lack of in vivo replication. These observations have
      significant implications for repeated administration of adenoviral vectors to the
      lungs of individuals with cystic fibrosis.

PMID- 7584082
TI  - Transduction of mobilized peripheral blood CD34+ cells with the
      glucocerebrosidase cDNA.
AB  - Gaucher disease (GD), the most common human lysosomal storage disorder, results
      from a genetic deficiency of the enzyme glucocerebrosidase (GC). The cloning of
      human GC cDNA, the benefits of allogeneic bone marrow transplantation and the
      success of enzyme replacement therapy support the feasibility of gene therapy as
      an approach to a cure for GD. We report the transfer of the GC gene to mobilized
      human peripheral blood (PB) CD34+ cells obtained from patients primed with
      granulocyte colony-stimulating factor and/or chemotherapy. A tenfold enrichment
      of CD34+ cells was achieved using an avidin-biotin immunoadsorption technique.
      Prestimulation of the CD34+ cells with cytokines, followed by infection for 5
      days with a supernatant containing the MFG-GC retroviral vector, resulted in
      enzyme activity up to 2.5-times greater than non-infected and lac-Z infected
      controls. Southern blot hybridization of DNA from these cells demonstrated a
      transduction efficiency of 10-30%. These studies show that the GC gene is
      transferred efficiently to mobilized PB CD34+ cells by the MFG-GC retroviral
      vector and results in expression of enzyme activity in the population of cells
      capable of bone marrow reconstitution. These results advance the development of
      gene therapy for GD.

PMID- 7584083
TI  - Block of HIV-1 infection by a combination of antisense tat RNA and TAR decoys: a
      strategy for control of HIV-1.
AB  - The tat gene product (Tat) of HIV-1 is an early regulatory protein necessary for
      viral gene expression and replication. Tat may also play a role as an
      extracellular protein in both HIV-1 replication and AIDS-associated disorders
      such as Kaposi's sarcoma. Thus, Tat represents a good target for gene therapy
      against AIDS. Here we show that when vectors expressing antisense tat RNA are
      transiently transfected into CD4+ cells, they block about 70% of HIV-1
      replication and inhibit the rescue of Tat-defective HIV-1 proviruses by
      inhibition of Tat protein expression and consequent lack of transcriptional
      activation of the HIV-promoter. However, antisense tat vectors cannot block the
      activity of extracellular Tat protein. Another tat inhibitory construct (poly-Tat
      activation response; TAR) previously suggested to inhibit HIV-1 transactivation
      by sequestering the Tat protein, inhibited the activity of extracellular Tat, but
      like antisense tat RNA did not completely block viral gene expression and
      replication. These results suggested that one mode of inhibition is not
      sufficient to block Tat function. However, when the antisense tat and the poly
      TAR constructs were combined HIV-1 gene expression was completely blocked (94
      98%), suggesting that a combination of inhibitory genes blocking Tat by
      sequential steps may be a better approach for AIDS gene therapy.

PMID- 7584084
TI  - The promise and overpromise of human gene therapy.

PMID- 7584086
TI  - Tumor cell bystander killing in colonic carcinoma utilizing the Escherichia coli
      DeoD gene to generate toxic purines.
AB  - Inefficiency of gene delivery, together with inadequate bystander killing,
      represent two major hurdles in the development of a toxin-mediated gene therapy
      for human malignancy. The product of the Escherischia coli DeoD gene (purine
      nucleoside phosphorylase, PNP) differs from the mammalian enzyme in its substrate
      specificity and is capable of catalyzing the conversion of several non-toxic
      deoxyadenosine analogs to highly toxic adenine analogs. We have found that
      expression of E. coli PNP in < 1% of a human colonic carcinoma cell line leads to
      the death of virtually all bystander cells after treatment with 6-methyl-purine
      2'-deoxyribonucleoside, a deoxyadenosine analog that is a substrate for E. coli
      PNP but not human PNP. Minimal toxicity was observed in non-transfected or E.
      coli LacZ transfected cells that were treated with this compound. These results
      establish a rational approach to achieve significant bystander killing, even
      after gene transfer to only a small fraction of tumor cells.

PMID- 7584087
TI  - Lipopolysaccharide is a frequent contaminant of plasmid DNA preparations and can
      be toxic to primary human cells in the presence of adenovirus.
AB  - Endotoxin (lipopolysaccharide, LPS) is commonly found as a contaminant in plasmid
      DNA preparations. We demonstrate here that the quantities of LPS typically
      contaminating DNA preparations can generate a toxicity to primary cells (primary
      human skin fibroblasts, primary human melanoma cells) in the presence of entry
      competent adenovirus particles. Toxicity can be observed with as little as 100
      ng/ml free LPS or 100 pg/ml LPS when the LPS is assembled into
      polylysine/adenovirus complexes. Simple and effective methods of removing the
      contaminating LPS using either a polymyxin B resin or Triton X-114 extraction are
      described. Treatment of DNA samples to remove LPS eliminates the toxicity to
      primary cells.

PMID- 7584085
TI  - Strategies to achieve targeted gene delivery via the receptor-mediated
      endocytosis pathway.
AB  - Gene transfer to eukaryotic cells may be accomplished by capitalizing on
      endogenous cellular pathways of macromolecular transport. In this regard,
      molecular conjugate vectors have been developed which deliver DNA via the
      receptor-mediated endocytosis pathway. An attractive feature of this vector
      system is the potential to achieve targeted gene delivery based upon flexible
      incorporation of a targeting ligand. In this review we describe steps that have
      been taken to optimize this vector system. Specific strategies include the
      incorporation of mechanisms to achieve conjugate escape from the endosome and the
      derivation of methods to eliminate sources of nonspecificity. These developments
      have demonstrated the potential to construct a vector system in which multiple
      independent components may function in a concerted manner to accomplish targeted
      high efficiency gene delivery. In their present state of development, molecular
      conjugate vectors may have many potential applications for in vitro use.

PMID- 7584090
TI  - Expression of the human glucocerebrosidase and arylsulfatase A genes in murine
      and patient primary fibroblasts transduced by an adeno-associated virus vector.
AB  - We have constructed two recombinant adeno-associated virus (AAV) vectors (pJJ-3GC
      and pJJ-3ASA) which contained either the human glucocerebrosidase (GC) or
      arylsulfatase A (ASA) cDNA under the control of an SV40 promoter. These plasmids
      were co-transfected to 293 cells with a helper plasmid containing trans-acting
      AAV genes required for packaging the vectors. The two recombinant vectors
      successfully infected murine and patient fibroblasts. The human
      glucocerebrosidase and arylsulfatase A genes were expressed at high levels in the
      cells as determined by Western blot analysis, enzyme assay and immunochemical
      staining. GC enzyme activity in Gaucher patient fibroblasts (GM-0877) infected by
      AAV-GC was 15-fold higher than in non-infected cells. ASA enzyme activity in MLD
      557g cells infected by AAV-ASA was up to 500-fold higher than in the
      metachromatic leukodystrophy (MLD) control cells. Southern blotting results
      showed that the vector integrated 1-2 copies of pJJ-3GC and ASA in the targeted
      cell genome. These two vectors will be useful in studying AAV-mediated transfer
      of the GC and ASA genes in cells and animals.

PMID- 7584088
TI  - Gene therapy for phenylketonuria: phenotypic correction in a genetically
      deficient mouse model by adenovirus-mediated hepatic gene transfer.
AB  - Classical phenylketonuria (PKU), which predisposes affected individuals to severe
      mental retardation, is caused by a deficiency of hepatic phenylalanine
      hydroxylase (PAH). A recombinant adenoviral vector containing the human PAH cDNA
      was constructed and administered to PAH-deficient mice (strain PAHenu2). The
      hyperphenylalaninemic phenotype of these animals was completely normalized within
      1 week of treatment. Although this therapeutic effect did not persist, analysis
      of the relationship between hepatic PAH activity and serum phenylalanine levels
      indicated that only 10-20% of normal enzymatic activity in the mouse liver is
      sufficient to restore normal serum phenylalanine levels. These results
      demonstrate that PKU and other metabolic disorders secondary to hepatic
      deficiencies can be completely corrected by gene therapy when more persistent
      vector systems are developed.

PMID- 7584089
TI  - Receptor-mediated gene delivery employing lectin-binding specificity.
AB  - Selective targeting of malignant cells will be necessary to implement many of the
      gene therapy strategies being designed to combat cancer. Targeting can be
      achieved by transductional or transcriptional approaches. Transductional
      targeting can be accomplished by exploiting differences in the molecules or
      receptors expressed on the cell surface of malignant versus normal cells. Given
      that malignant cells can be distinguished from normal by differences in the
      expression of cell surface carbohydrates, we hypothesized that transductional
      targeting would be feasible by molecular conjugate vectors which achieve cell
      binding by virtue of lectins directed against the cell surface glycocalyx. We
      have shown that gene transfer can be accomplished by these novel lectin-targeted
      molecular conjugate vectors and that lectin binding specificities may serve as a
      means for potential targeting of cancer cells for the purposes of gene therapy.

PMID- 7584092
TI  - Germline gene therapy?

PMID- 7584091
TI  - Gene therapy for Lewis lung carcinoma with tumor necrosis factor and interleukin
      2 cDNAs co-transfected subline.
AB  - Gene therapy with cytokine cDNA will provide a new tool for cancer treatment. We
      have already reported that immunization with interleukin-2 (IL2) cDNA transfected
      Lewis lung carcinoma (LLC) cells induced anti-tumor immunity, which, however, was
      not strong enough to eradicate an established tumor. In an attempt to develop
      more effective gene therapy methods, we have used tumor cells co-transfected with
      IL-2 and tumor necrosis factor (TNF) cDNAs. These cDNAs were introduced into pBMG
      Neo and pcDV-X819 vectors, respectively, and then co-transfected into LLC cells.
      The co-transfectants were selected by incubating them in a medium containing G418
      followed by the limiting dilution method twice to obtain IL2 and TNF cDNA co
      transfected LLC (LLC-TNF-IL2) cells. When 5 x 10(5)/ml LLC-TNF-IL2 cells were
      incubated for 48 h, they secreted 7.56 U/ml TNF and 527.0 U/ml IL2 into the
      culture supernatant. When C57BL/6 mice were transplanted with 1 x 10(6) LLC-TNF
      IL2 cells, all the tumors were rejected. The growth of transplanted LLC, but not
      B16F10 melanoma cells, was retarded in mice inoculated with LLC-TNF-IL2 on their
      contralateral sides, which suggests specific immunity was induced. The
      immunization effect by the co-transfectant was superior to that of the IL2- and
      TNF-transfectants alone.

PMID- 7584093
TI  - Inflammatory effects of gene transfer into the CNS with defective HSV-1 vectors.
AB  - The use of viral vectors which infect and express genes in post-mitotic neurons
      is a potential strategy for the treatment of disorders affecting the central
      nervous system (CNS). However, the inflammatory consequences of such strategies
      have yet to be systematically examined. Preparations of non-replicating defective
      herpes simplex virus type 1 (HSV-1) amplicon vectors containing the lacZ gene
      were obtained by standard methods and stereotaxically injected into the adult rat
      dentate gyrus (DG). The consequent gene expression and inflammatory effects
      following microinjection were investigated. beta-Galactosidase activity was
      detected in neurons of the DG from 24 h to at least 12 days after vector
      injection. A strong inflammatory response developed within 2 days, characterized
      by diffuse up-regulation of major histocompatibility complex (MHC) class I
      antigens and the activation of microglia. After 4 days the recruitment of MHC
      class II+ cells, activated T lymphocytes and macrophages was detected. These
      features persisted for at least 31 days. Of importance was the finding of beta
      galactosidase activity in a bilateral group of neurons in the supramammillary
      nuclei (SMN) of the posterior hypothalamus, known to send afferent projections to
      the DG. The onset of inflammation at this secondary site was delayed, but its
      cellular characteristics resembled those found at the primary site of injection.
      Thus, the use of preparations of defective HSV-1 vectors for gene transfer in the
      CNS has immunological implications both at primary and secondary sites within the
      CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584096
TI  - A comparison of the properties of different retroviral vectors containing the
      murine tyrosinase promoter to achieve transcriptionally targeted expression of
      the HSVtk or IL-2 genes.
AB  - To target therapeutic genes specifically to melanoma cells, we have constructed
      recombinant retroviruses where transcriptional control of the murine interleukin
      2 (mIL-2) or herpes simplex virus thymidine kinase (HSVtk) genes is provided by
      the 5' promoter region of the murine tyrosinase gene. Tissue-specific expression
      of these genes is observed both at the mRNA and protein levels in the B16
      melanoma line compared with NIH3T3 fibroblasts. Thus, B16 cells infected with one
      such retrovirus containing the HSVtk gene exhibited a > 90% reduction in colony
      forming efficiency after exposure to 1 microgram/ml ganciclovir, relative to
      controls, whereas similarly infected NIH3T3 cells showed < 10% reduction in
      colony-forming efficiency under comparable conditions. The degree of preservation
      of tissue-specific expression from the internal tyrosinase promoter depended upon
      the exact molecular design of the vector, possibly as a consequence of the
      interference between closely juxtaposed promoters within the provirus. Our
      results show that retroviral vectors can be prepared with the capacity to
      regulate expression of inserted genes specifically in a particular cell type and
      may be useful for developing efficient, targeted vectors for the in vivo delivery
      of genetic therapies for malignant melanoma.

PMID- 7584097
TI  - Transplantation of retrovirus-transduced canine keratinocytes expressing the beta
      galactosidase gene.
AB  - We studied transplantation of retrovirus vector transduced canine keratinocytes
      to determine whether keratinocytes could persist and express the transferred gene
      after superficial transplantation to full-thickness wounds of dogs, a large
      random-bred model for gene transfer studies. Canine keratinocytes were transduced
      by co-cultivation with PA317 retrovirus packaging cells which produced helper
      free amphotropic retroviral vectors (LZSN and LNPOZ) encoding the genes for beta
      galactosidase (beta-gal) and neomycin phosphotransferase (neo). Efficient
      transfer and expression of the two genes could be demonstrated in confluent
      keratinocyte cultures for both vectors. When transduced keratinocytes were grown
      in organotypic cultures on a collagen matrix containing autologous dermal
      fibroblasts at the air-liquid interface, the cultures showed well-organized and
      defined epidermal cell layers and several markers of terminal differentiation,
      including the presence of keratohyalin granules and a multilayered stratum
      corneum. To determine whether the transferred beta-gal gene was also expressed in
      vivo, we performed autologous transplantation of transduced keratinocytes onto
      full-thickness wounds of dogs. beta-Gal expressing keratinocytes could be
      demonstrated in situ in the regenerating epidermis 2 weeks after transplantation.
      We conclude that keratinocytes can be efficiently transduced by retroviral
      vectors, that retroviral transduction does not interfere with proliferation or
      differentiation, and that transduced keratinocytes express the transferred gene
      after transplantation to full-thickness skin wounds of dogs. Keratinocytes thus
      seem to be good target cells for gene therapy.

PMID- 7584094
TI  - Cell targeting with retroviral vector particles containing antibody-envelope
      fusion proteins.
AB  - Retroviral vectors are the most efficient tool to introduce genes into vertebrate
      cells. However, their use is limited by the host range of the retrovirus from
      which they were derived. To alter the host range of the vector particle, we
      developed a method to substitute the receptor-binding domain of the envelope
      protein of a retrovirus with an antigen-binding site of an antibody. To test
      whether such particles are competent for infection, we established a model system
      using an antigen-binding site of an antibody against the hapten dinitrophenol
      (DNP). Retroviral vector particles containing such chimeric envelope proteins
      were able to bind to and infect cells that were not infectable with wild-type
      virus after DNP was conjugated to the cell surface. They did not infect such
      cells without DNP conjugation. Control experiments with chimeric envelope
      proteins of ecotropic murine leukemia virus (eco-MLV) and spleen necrosis virus
      (SNV) indicate that the pathway of virus entry of scA-env-containing virus
      particles was different from that of wild-type virus.

PMID- 7584095
TI  - An in vitro ligation and transfection system for inserting DNA sequences into the
      latency-associated transcripts (LATs) gene of herpes simplex virus type 1.
AB  - This report describes a simple, rapid and highly efficient method for introducing
      specific DNA sequences into a defined locus of the herpes simplex virus type 1
      (HSV-1) genome by restriction enzyme cleavage and ligation. The genome of the HSV
      1 strain HFEM contains a 4.1 kb deletion in one copy of the RL region, deleting
      one copy of the latency-associated transcript (LAT) gene. It does not contain any
      site for restriction enzyme PacI. Two unique PacI restriction enzyme sites
      flanking an HSV-1 ICP6 promoter-LacZ reporter gene cassette were engineered into
      the LAT region to generate a recombinant virus HFEM/ICP6-LacZ which produced blue
      plaques in the presence of X-gal. This viral vector allowed the insertion of
      foreign genes directly into the HSV-1 genome by restriction enzyme digestion and
      ligation. The system was tested by digesting the HFEM/ICP6-LacZ DNA with PacI and
      with SwaI (an endogenous unique restriction enzyme site upstream of the LAT
      promoter locus and inserting by in vitro ligation a LAT promoter-LacZ gene
      cassette into the HFEM/ICP6-LacZ genome. The new recombinant virus HFEM/LAT-LacZ
      was detected as white plaques in the presence of X-gal, since beta-galactosidase
      expression, when driven by the LAT promoter, is not detectable during viral
      replication in tissue culture. The high yield (approximately 100%) of the
      recombinant virus obtainable from this in vitro ligation and transfection
      procedure coupled with a blue-white or reversible white-blue plaque detection
      scheme makes this a powerful method for constructing HSV-1 vectors around the LAT
      promoter locus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584098
TI  - Antitumor activity and reporter gene transfer into rat brain neoplasms inoculated
      with herpes simplex virus vectors defective in thymidine kinase or ribonucleotide
      reductase.
AB  - Herpes simplex virus (HSV) mutants or recombinant vectors might be useful
      oncolytic agents. Three general types of HSV vectors can be potentially used for
      this purpose: (1) mutants in viral transcription factors, such as ICP0 and ICP4;
      (2) mutants in enzymes involved in nucleic acid metabolism, such as thymidine
      kinase (TK) and ribonucleotide reductase (RR); and (3) mutants in neurovirulence
      factors, such as gamma 34.5. We tested the destructive ability of each type
      against rat 9L gliosarcoma cells in culture. We found that the HSV vectors
      defective in TK or RR were more efficient at tumor cell lysis in culture than the
      other types of HSV vectors. This increased efficiency provided the rationale for
      evaluating the TK and RR mutants in vivo following their stereotactic inoculation
      into 9L gliosarcomas implanted in rat brains. We employed the X-gal enzymatic
      histochemical assay to show that HSV-mediated lacZ gene expression was present in
      cells within the tumor mass in a relatively selective fashion. Immunoreactive HSV
      capsid and core antigens were present both in cells within the tumor, as well as
      in cells such as neurons and astrocytes, directly adjacent to the tumor mass.
      Long-term survival studies revealed that rats treated with either the TK or RR
      mutant lived significantly longer than control rats (p = 0.014, Kruskal-Wallis
      one-way analysis of variance). These results indicate that HSV vectors, defective
      in enzymes needed in nucleic acid metabolism, can preferentially mediate lacZ
      gene expression in cells within the tumor. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584099
TI  - Intracellular single-chain antibody directed against erbB2 down-regulates cell
      surface erbB2 and exhibits a selective anti-proliferative effect in erbB2
      overexpressing cancer cell lines.
AB  - Overexpression of the tyrosine kinase receptor erbB2 is important in the
      pathogenesis of a variety of neoplasms. Based on this concept, targeted anti
      cancer strategies have been designed to selectively eradicate erbB2
      overexpressing tumor cells. These strategies have employed either monoclonal
      antibodies or antibody toxin molecules with specificity for the cell surface
      erbB2 protein. As an alternative strategy, anti-erbB2 single-chain immunoglobulin
      (sFv) genes were constructed to direct expression of intracellular anti-erbB2
      antibodies. Expression of an endoplasmic reticulum (ER) form of the anti-erbB2
      sFv resulted in a profound down-regulation of cell surface erbB2 in an erbB2
      overexpressing ovarian carcinoma cell line. In addition, expression of the
      intracellular antibody resulted in marked inhibition of tumor cell proliferation.
      Whereas stable transfectants expressing the anti-erbB2 sFv could be dervied from
      non-erbB2 overexpressing cancer cell lines, expression of the intracellular
      antibody was incompatible with long-term survival of the erbB2 overpressing tumor
      cells. The ability to selectively 'knock-out' erbB2 demonstrates that cell
      surface localization of erbB2 is essential to its ability to induce aberrant
      cellular proliferation in tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584100
TI  - Cultured human myoblasts and myotubes show markedly different transducibility by
      replication-defective adenovirus recombinants.
AB  - Human adenovirus (AV) is a favored vector for delivery of therapeutic genes into
      certain target cells, such as skeletal muscle cells for gene therapy. Here we
      show that replication-defective (E1 + E3 deleted) human type 5 adenovirus (AV)
      recombinants containing a reporter gene insert (RSV-luciferase or RSV-Lux) can
      very efficiently transduce cultured human myoblasts. However, transduction
      efficiency is about one order of magnitude less in cultured myotubes 16 days
      postfusion. The high transduction of myoblasts by AV-RSV-Lux could be effectively
      blocked by an arginine-glycine-asparagine (RGD) oligopeptide that serves as a
      ligand for the natural internalization receptor of AV. The normalized level of
      beta 3/beta 5-integrin, the main component of the internalization receptor for AV
      is about three times as abundant in myoblasts than in myotubes. This could
      contribute, among other things, to the relatively high susceptibility of
      myoblasts to AV infection and AV-mediated gene transduction.

PMID- 7584101
TI  - Guidance on making research proposals to conduct gene therapy research on human
      subjects. Gene Therapy Advisory Committee.

PMID- 7584103
TI  - The use of DNA viruses as vectors for gene therapy.
AB  - The need for efficient transfer of potentially therapeutic genes to defined cell
      populations has stimulated the development of vectors based on viruses. To date,
      most effort has been spent on the RNA-containing retroviruses. These viruses,
      however, possess a number of disadvantages including an inability to infect
      nondividing cells as well as having potential for oncogenicity and insertional
      mutagenesis of host cell genes due to random chromosomal integration. These
      disadvantages have led to the development of vectors based on DNA-containing
      viruses such as adenovirus, herpes simplex virus and parvovirus. These viruses
      possess a number of attributes favourable to their use in gene therapy.
      Adenoviruses, for example, were first considered as potential vectors for the
      genetic treatment of lung conditions due to their natural affinity for
      respiratory epithelium. However, other features including their ability to be
      prepared at high titres, to direct high levels of foreign gene expression and
      their extrachromosomal existence has resulted in their development for the
      treatment of numerous other diseases. In many studies, adenovirus vectors have
      been shown to efficiently infect target cell populations and to express proteins
      at therapeutic levels in the absence of significant toxicity. The ability of
      herpes simplex virus to reside in neurons in a latent state that does not appear
      to affect normal cellular physiology has sparked interest in this virus as a
      potential vector in the treatment of neurological disorders. A subgroup of
      parvoviruses, namely the adeno-associated viruses, have a prediliction for
      integration at a defined chromosomal location and may represent a safer
      alternative to retroviruses.

PMID- 7584102
TI  - UK guidelines for gene therapy.

PMID- 7584105
TI  - The impact of developmental stage, route of administration and the immune system
      on adenovirus-mediated gene transfer.
AB  - Important aspects of successful adenovirus gene transfer include the amount and
      persistence of gene expression, the ability to readminister virus and the
      localization of virus-directed gene expression to target organs. Our objective in
      this study was to use a single recombinant adenovirus bearing a quantifiable
      reporter gene [chloramphenicol acetyltransferase (CAT)] to establish the
      parameters which define the limits of adenovirus gene expression in a rat model.
      First, we determined how the route of virus administration affected the amount,
      duration and distribution of expression in different tissues and in rats of
      different developmental stages. All routes resulted in infection of all tissues
      tested. Surprisingly, the most efficient and widespread gene transfer was
      achieved by intracardiac muscle injection. The high levels of CAT protein that
      can be produced in a liver (< or = 1.7 mg) or a heart (< or = 196 micrograms) 5
      days after infection suggest that the amount of gene product will not be a
      limitation in the use of adenovirus. Following peak activity at 5 days after
      infection, a gradual decline of CAT expression was observed in all tissues
      assayed; by 80 days neither CAT activity nor adenovirus DNA were detectable. In
      addition, adults could not be boosted by a second administration of virus,
      presumably due to the presence of high levels of neutralizing antibodies. The
      limited persistence of gene expression could be circumvented when virus was
      injected into neonates. Blocking T lymphocyte expansion by cyclosporine enhanced
      the persistence of CAT gene product over a 25-day period in heart and lung but
      not in liver compared with control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584106
TI  - Suppression of various human tumor cell lines by a dominant negative H-ras
      mutant.
AB  - A dominant negative H-ras mutant, N116Y, was transfected into a variety of human
      tumor cell lines. N116Y extremely inhibited the proliferation of A431 (vulva),
      PC3 (prostate), T24 (bladder), MCF7 (breast), NKPS and TMK1 (stomach) cancer cell
      lines. A431 and PC3 cells were particularly susceptible to N116Y. In order to
      examine the effects of N116Y on the neoplastic phenotypes, we transfected a less
      efficient N116Y expression vector into A431 cells. Almost all clones survived
      after G418 selection. However, they did not retain the N116Y gene and only one
      clone faintly expressed N116Y. This N116Y-expressing clone had no tumorigenicity
      in vivo, and revealed deformed morphology and DNA fragmentation, suggesting that
      N116Y might have induced apoptotic cell death. Thus, N116Y may be applicable for
      gene therapy of a wide spectrum of human tumors.

PMID- 7584104
TI  - In vivo adenovirus-mediated transfer of human CFTR cDNA to rhesus monkey airway
      epithelium: efficacy, toxicity and safety.
AB  - We have administered replication defective recombinant adenovirus harboring the
      human CFTR cDNA (Ad.CFTR) to lungs of Rhesus monkeys and assessed toxicity,
      efficiency of gene transfer and containment of recombinant adenovirus in the
      lungs. Gene transfer efficiencies, as measured by PCR analysis, were dose
      dependent. Administration of low dose Ad.CFTR [1.5 x 10(7) plaque forming units
      (p.f.u.)] was not accompanied by any clinical chemical or histopathological
      changes. Mild to moderate multifocal perivascular and peribronchial lymphocytic
      infiltrates were found upon histopathological analysis only after administration
      of a high dose of recombinant adenovirus, although not accompanied by changes in
      clinical chemical parameters. Long-term expression (up to 128 days) was found
      after administration of recombinant adenovirus. Re-challenging of the monkeys
      treated with high-dose recombinant adenovirus resulted again in gene transfer at
      all levels of lungs and airways, without being accompanied by additional
      histopathological changes. Circulating anti-adenovirus antibodies were elicited.
      Animals treated with high-dose adenovirus secreted virus in pharynx and faeces
      for maximally 2 and 4 days after administration, respectively. These results show
      that recombinant adenovirus can be used for efficient delivery of genes into
      primate airway epithelium without signs of severe toxicity.

PMID- 7584107
TI  - Transgene expression in the coronary circulation: transcatheter gene delivery.
AB  - Therapeutic and research applications of direct gene transfer in the coronary
      vasculature are limited by varying transgene activity found in the vessel wall.
      It remains to be determined whether this is due to difficulties in delivery of
      recombinant DNA into the coronary arteries or if it relates to the state of
      recipient cells in the arterial wall. Accordingly, using a clinically applicable
      protocol, we have examined the time course of transgene (luciferase) expression
      in porcine coronary vasculature following transcatheter gene transfer (1 day to 4
      weeks). Liposome-mediated transfection by means of a transcatheter approach
      resulted in detectable luciferase activity in all transfected vessels at 1 day
      after gene delivery. However, the activity of a reporter gene rapidly declined at
      7 days thereafter, with only 33% of coronary arteries demonstrating luciferase
      activity. Comparable levels of transgene sequences were present in transfected
      vessels, although no correlation with luciferase activity was found. To further
      determine possible mechanisms responsible for rapidly declining transgene
      expression in vivo, cell proliferation was induced in the vessel wall by means of
      either balloon denudation or by intramural injections of platelet derived growth
      factor BB (PDGF-BB) into the porcine coronary vasculature at the time of gene
      transfer. Luciferase activity was significantly augmented (23-fold) following
      mitogenic stimulation in vivo as compared with the control transfected coronary
      arteries. These data demonstrate that a practical transcatheter approach provides
      an effective route to deliver recombinant DNA sequences into the coronary
      arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584108
TI  - Rigor in gene therapy studies.

PMID- 7584109
TI  - Adeno-associated virus vectors for gene therapy.
AB  - Adeno-associated virus type 2 (AAV) is a non-pathogenic DNA virus which has been
      utilized as a eukaryotic gene transfer vector in vitro and in vivo. AAV possesses
      a unique set of characteristics which may make it useful for human gene therapy.
      AAV infection does not require host cell proliferation, although expression from
      AAV vectors may exhibit a relative preference for actively dividing cells. Both
      wild-type AAV and AAV vectors tend to persist in infected cells for prolonged
      periods of time, without any significant adverse consequences for the host. Wild
      type AAV integrates frequently in one specific region of chromosome 19, whereas
      rep-deleted AAV vectors integrate in a less specific fashion in the host cell
      genome and may also persist in an episomal state. AAV vectors have been used to
      transduce a wide range of cell types in vitro including respiratory epithelial
      cells as well as bone marrow and lymphocyte-derived cells. As a prelude to AAV
      based gene therapy for cystic fibrosis (CF), in vivo transduction and expression
      in the lungs has been observed in rodents and non-human primates after direct
      delivery to the airway surface, without any detectable toxicity. Based on these
      findings, the National Institutes of Health Recombinant DNA Advisory Committee
      (RAC) has recently approved a phase I human trial of CF gene therapy using an AAV
      vector.

PMID- 7584112
TI  - Inhibition of HIV-1 in CEM cells by a potent TAR decoy.
AB  - TAR decoys are short RNA oligonucleotides, corresponding to the HIV TAR sequence,
      which inhibit HIV expression and replication by blocking the binding of the HIV
      regulatory protein Tat to the authentic TAR region. In previous studies, TAR
      decoys expressed from a tRNA polIII promoter were moderately effective at
      inhibiting HIV in isolated human T cell lines and less effective at inhibiting
      HIV in peripheral blood CD4+ T cells. In this study, a series of modifications
      was introduced into the tRNA expression cassette in order to improve their
      effectiveness. These modifications included the addition of sequences which are
      predicted to have stem-loop secondary structures and addition of a wild-type tRNA
      processing site. TAR decoy RNA expressed in CEM cells from modified tRNA-based
      expression cassettes yielded five- to 20-fold more TAR transcripts than
      unmodified tRNA-based expression cassettes. HIV replication, as measured by a
      flow cytometric method to quantify intracellular viral p24 expression, was
      significantly reduced in polyclonal populations of CEM cells expressing a
      modified tRNA-TAR transcript that contains a wild-type tRNA processing site and
      stem-loops 5' and 3' to the TAR sequence. Similar modifications to the tRNA
      expression cassette also increased the intracellular concentration of a random
      test oligonucleotide, indicating that this improved expression system may also be
      useful for antisense and ribozyme based gene inhibition strategies.

PMID- 7584111
TI  - A new reporter system for detection of retroviral infection.
AB  - We describe a novel reporter molecule, the murine surface antigen Thy-1, useful
      for immunoselection and detection of retrovirus-mediated transduction by flow
      cytometry. A cDNA encoding the murine thy-1 gene was isolated, and cell surface
      expression of its gene product was demonstrated. The Thy-1 glycoprotein was
      tested as a cell surface reporter molecule in the context of replication
      defective and -competent retroviruses. Cells transduced via murine retroviral
      vectors carrying the thy-1 and the neomycin phosphotransferase genes express Thy
      1 glycoprotein on their surfaces. The Thy-1 marker is potentially useful in gene
      transfer protocols because selection of transduced cells can be achieved by
      immunoselection with anti-Thy-1 antibodies shortly after infection with the
      retroviral vector. In addition, a human immunodeficiency virus type 1 (HIV-1)
      recombinant expressing Thy-1 is described, which is replication-competent and
      syncytium-inducing in human peripheral blood mononuclear cells (PBMCs) and
      immortalized CD4-positive cell lines. Cells infected with this HIV-1 recombinant
      express Thy-1 on their surfaces and can be detected and purified by fluorescence
      activated cell sorting (FACS). Because of these properties, retroviruses
      expressing this genetic marker can be useful for studies in gene therapy and of
      the retroviral life-cycle.

PMID- 7584113
TI  - Herpes simplex virus type 1 vector mediated gene transfer to muscle.
AB  - Herpes simplex virus type 1 (HSV-1) has a broad host range although in natural
      human infections the virus is neurotropic, establishing latent infections in
      sensory neurons where the viral DNA persists as an intact episome. The
      establishment of latency does not depend on viral replication functions,
      suggesting that infection of non-neuronal cells, including tissue of myogenic
      origin, by replication defective mutants may result in genome persistence in a
      similar episomal state. In this report a replication defective HSV-1 recombinant
      vector containing the beta-galactosidase reporter gene under transcriptional
      control of the strong human cytomegalovirus immediate-early gene promoter (HCMV
      IEp-lacZ) was used to infect muscle cells in vitro and in vivo. This replication
      defective mutant virus (d120), deleted for both copies of the essential immediate
      early gene (ICP4) and thus incapable of expressing early and late viral genes,
      displayed highly reduced cytotoxicity in myogenic cells. This vector infected
      both myoblasts and myotubes in culture with transgene expression persisting for
      at least 8 days. The transduction efficiency in myotubes was similar to myoblasts
      at several multiplicities of infection (MOIs), suggesting that HSV could infect
      differentiated muscle fibers and that myoblast differentiation would neither
      prevent expression of the cellular receptor(s) for the virus nor inhibit viral
      penetration. Direct inoculation of mouse muscle fibers in vivo with 10(6) to
      10(8) plaque forming units (p.f.u.) of vector was sufficient to transduce
      significant numbers of muscle fibers in newborn mice and some fibers in adult
      normal and mdx mice. These results suggest that recombinant HSV-1 vectors may be
      useful for gene transfer to muscle.

PMID- 7584110
TI  - Overexpression of arylsulfatase A gene in fibroblasts from metachromatic
      leukodystrophy patients does not induce a new phenotype.
AB  - We tested the influence of overexpression of arylsulfatase A (ASA) on the
      activity of other sulfatases in fibroblasts from patients with metachromatic
      leukodystrophy (MLD). We demonstrated that the overexpression of ASA reduces the
      activity of various sulfatases by a small amount but does not induce an
      accumulation of glycosaminoglycan. Our results indicate that influence of ASA
      overexpression on other sulfatases is different from that of N-acetyl
      galactosamine-4-sulfatase overexpression reported by Anson et al. We conclude
      that gene therapy for MLD based on the transfer of a normal ASA gene to mutant
      cells will be feasible because the overexpression of ASA peptides in cells does
      not lead to profound deficiency of other sulfatases or result in a new phenotype.

PMID- 7584115
TI  - Systemic delivery of a recombinant protein by genetically modified mesothelial
      cells reseeded on the parietal peritoneal surface.
AB  - To evaluate the ability of genetically modified peritoneal mesothelial cells to
      deliver recombinant proteins to the systemic circulation, we used our previously
      described mesothelial cell-based ex vivo gene therapy strategy. Rat primary
      peritoneal mesothelial cells, isolated from parietal peritoneum by enzymatic
      digestion, were stably transfected (using strontium phosphate DNA co
      precipitation) with the plasmid pSVTKgh to express a secreted reporter gene
      product, human growth hormone (hgh). Such hgh-secreting mesothelial cells were
      reseeded on the denuded peritoneal surface of syngeneic recipients and delivery
      of the reporter gene product to the systemic circulation was monitored by
      analysis of serum samples for the presence of hgh at various times after
      mesothelial cell implantation. Polymerase chain reaction (PCR) analysis
      demonstrated that the hgh-transfected mesothelial cells repopulated the denuded
      areas and remained attached there for at least 12 weeks. Moreover, these
      genetically modified mesothelial cells continued to express the reporter gene
      product in vivo and secreted hgh in sufficient quantity to be detected in the
      systemic circulation (ie statistically significant amounts of hgh could be
      measured in the serum of cyclosporine A-treated rats for at least 2 months; Mann
      Whitney test, P < 0.05). Our results demonstrate the successful, sustained,
      systemic delivery of a recombinant protein by genetically modified peritoneal
      mesothelial cells following their reattachment to the peritoneal surface, and
      suggest the potential of ex vivo mesothelial cell-mediated gene therapy for the
      treatment of inherited or acquired disorders requiring delivery of therapeutic
      proteins to the circulation.

PMID- 7584114
TI  - Mesothelial cell-mediated gene therapy: feasibility of an ex vivo strategy.
AB  - We have developed a model system in the rat to test the feasibility of
      recombinant protein expression by genetically modified peritoneal mesothelial
      cells following autologous peritoneal implantation. Rat primary peritoneal
      mesothelial cells, isolated from parietal peritoneum by enzymatic digestion, were
      stably transduced (using a Moloney murine leukemia virus (MoMLV)-derived
      retroviral vector, BAG, expressing the Escherichia coli lacZ gene) to mark the
      cells with a reporter protein (beta-galactosidase, beta-gal). Such transduced
      mesothelial cells, tagged with DiO, a fluorescent lipophilic dye used for long
      term tracing of transplanted cells, were then reseeded on the denuded peritoneal
      surface of syngeneic recipients. DiO-labeled, BAG-transduced mesothelial cells
      were observed to repopulate the denuded areas and remain attached there for > 90
      days. Moreover, these genetically modified mesothelial cells continued to express
      the reporter gene product in vivo (ie beta-gal activity was present for at least
      1 month). Our results demonstrate the feasibility of ex vivo gene therapy using
      peritoneal mesothelial cells.

PMID- 7584116
TI  - Organoids direct systemic expression of erythropoietin in mice.
AB  - Organoids are adenoviral vector transduced cells embedded ex vivo in a collagen
      polytetrafluoroethylene lattice that is saturated with angiogenic factors.
      Organoids provide an alternative method of cell mediated gene transfer following
      implantation in the donor/recipient. The feasibility of adenovirally mediated
      delivery via organoids using the erythropoietin (Epo) cDNA was tested.
      Fibroblasts were transduced by two recombinant adenoviral vectors encoding the
      Macaca cynomolgus Epo cDNA, driven by a viral (RSV LTR) or a murine housekeeping
      gene promoter (PGK-1). A functional in vivo assay was used to monitor Epo
      production via the rise in hematocrit(s) (hct). The hct remained elevated for as
      long as 6 weeks after implantation. Subcutaneous implants gave consistently
      higher hct than intraperitoneal implants, while organoids made with a greater
      number of cells, or an equal number of cells transduced at higher multiplicities
      of infection (MOI) also produced a larger increase in hct. AdPGKEpo-organoids
      produced a greater increase in hct than AdRSVEpo-organoids under comparable
      conditions, but the duration of expression was similar. A 10- to 50-fold lower
      input of AdRSVEpo using organoids versus direct intravenous injections resulted
      in an equal to, or greater than hct response in mice. Explanted organoids caused
      a rapid decrease in the hct of mice. Organoid supernatant had little or no
      detectable free viral particles making this method safe from unwanted recombinant
      adenovirus dissemination.

PMID- 7584117
TI  - Gene delivery into the central nervous system by nasal instillation in rats.
AB  - Replication-deficient adenoviruses have been used successfully to transfer
      foreign DNA into postmitotic cells. This article demonstrates that it is possible
      to transfer the Escherichia coli lacZ gene in vivo into the central nervous
      system structures of rats after nasal instillation of replication-defective
      adenoviral vector AdRSV beta gal. Mitral cells from the olfactory bulb, neurons
      from the anterior olfactory nucleus, locus coeruleus and area postrema expressed
      beta-galactosidase for at least 12 days. No cytopathic effect was observed in the
      CNS structures studied at the viral titer used (1-3 x 10(9) plaque-forming units
      (p.f.u.)). This method could be useful for the gene therapy of diseases affecting
      different CNS structures.

PMID- 7584120
TI  - Therapeutic exploitation of genetic defects in haematological malignancies.

PMID- 7584118
TI  - Retrovirus mediated in vivo gene transfer to synovium in bacterial cell wall
      induced arthritis in rats.
AB  - Gene therapy may provide an effective alternative to conventional approaches for
      treating rheumatoid arthritis. Direct in vivo gene delivery to synovium has a
      distinct advantage with respect to clinical use. To date, retroviral vectors are
      the best studied constructs for gene delivery, and almost all approved gene
      therapy trials in humans rely on retroviral vectors. However, the applicability
      of retroviral transduction is limited by requirement for cell division, and
      attempts to transduce normal synovium in situ using retroviral vectors are
      reported to fail. The present study was undertaken in order to investigate
      susceptibility of inflamed synovium to retroviral infection in vivo. Using an
      experimental model of bacterial cell wall (BCW)-induced arthritis in rats, we
      attempted two approaches for delivery of retroviral vectors to synovium. In the
      first approach, recombinant retroviral vectors carrying reporter genes lacZ and
      neo were directly injected into inflamed rat ankle joints. Alternatively,
      inflamed joints were inoculated with gamma-irradiated murine retroviral vector
      producing packaging cells. We found that about 1% of cells in explants from
      joints inoculated with packaging cells were lacZ-neo-positive. The lacZ+ neo+
      cells in joint explants proliferated in culture and were of rat origin as
      determined using species-specific polymerase chain reaction (PCR) analysis. There
      was no evidence of transduction in explants from joints directly injected with
      retroviral vectors or from contralateral, control joints. These findings show
      that arthritic joints have a population of cells susceptible to retroviral
      infection in situ and demonstrate the possibility of using retroviral vectors for
      direct gene delivery to inflamed synovium.

PMID- 7584121
TI  - Expression of human interleukin-1 receptor antagonist in mouse lungs using a
      recombinant adenovirus: effects on vector-induced inflammation.
AB  - Pulmonary inflammation is a major obstacle to using adenovirus-based vectors for
      gene transfer to the lung. Since the pro-inflammatory cytokine, interleukin-1 (IL
      1), is expressed early following adenovirus infection, we hypothesized that
      inhibition of IL-1 might block the inflammation caused by adenoviral vectors. To
      inhibit IL-1 activity at the site of infection continuously, we employed a
      recombinant adenovirus that contained the cDNA for human IL-1 receptor antagonist
      protein (IL-1ra) designated as Ad.RSVIL-1ra. When Ad.RSVIL-1ra was instilled
      intratracheally into CBA/J mice, human IL-1ra was recovered in lung tissue and
      bronchoalveolar lavage fluid for up to 30 days. Human IL-1ra is known to bind to
      murine IL-1 receptors and inhibit IL-1-mediated responses. To measure pulmonary
      inflammation, the number of inflammatory cells contained within suspensions of
      protease-digested lung tissue were counted 6 days after virus administration.
      Ad.RSVIL-1ra failed to reduce the number of inflammatory cells below that induced
      by a control vector that lacked an expression cassette (Ad.BgIII). Light
      microscopy showed that the lung tissue from Ad.RSVIL-1ra and Ad.BgIII-treated
      mice contained qualitatively similar amounts of inflammatory infiltrate. We
      conclude that adenovirus-based vectors can be used to induce high levels of IL
      1ra expression within the lung, but such expression was unable to prevent
      adenoviral vector-induced inflammation.

PMID- 7584119
TI  - Increased titer of recombinant AAV vectors by gene transfer with adenovirus
      coupled to DNA-polylysine complexes.
AB  - One of the principal problems with using recombinant adeno-associated virus
      vectors (rAAV) as vehicles for gene delivery has been the difficulty in obtaining
      high-titer virus stocks after the initial transfection into producer cells. In
      this report we describe a method for transfecting cells at extremely high
      efficiency with rAAV vector DNA and complementation plasmid while simultaneously
      infecting those cells with replication competent adenovirus using adenovirus
      polylysine-DNA complexes. We further show that this technique results in an
      increase in rAAV transducing titer by two orders of magnitude over what is
      typically achieved by standard calcium phosphate transfection.

PMID- 7584122
TI  - Successful transduction of oligodendrocytes and restoration of arylsulfatase A
      deficiency in metachromatic leukodystrophy fibroblasts using an adenovirus
      vector.
AB  - Metachromatic leukodystrophy (MLD) is an inherited metabolic disease which is
      characterized by deficient activity of arylsulfatase A (ASA). This deficiency
      causes progressive accumulation of cerebroside sulfate (CS) in oligodendrocytes
      (OLs) in the brain resulting in dysmyelination. We are developing approaches for
      treating MLD based on direct delivery of ASA genes to brain. In this paper, we
      report a recombinant adenovirus (Adex1SRLacZL) that efficiently transduces OLs.
      Moreover, transduction and expression of the human transgene was efficient in
      primary fibroblasts from MLD patients exposed to similar recombinant adenovirus
      carrying the ASA gene (Adex1SRASA) In addition, the expressed ASA protein was
      correctly targeted to lysosomes and was immunoreactive to anti-ASA antibody. The
      enzymatic activity of ASA in MLD patient cells is corrected from the deficient
      state to 2.3 to 5.0 times the activity of normal control cells. These results
      demonstrate the correction of ASA deficiency by a recombinant adenovirus that is
      potentially useful for transferring the gene to brain.

PMID- 7584123
TI  - Intratracheal gene delivery to the mouse airway: characterization of plasmid DNA
      expression and pharmacokinetics.
AB  - Intratracheal administration of plasmid DNA resulted in gene expression in mouse
      airways in the absence of any enhancing agent. Administration of plasmid DNA
      encoding the chloramphenicol acetyltransferase gene (CAT) in sterile water lead
      to CAT transgene expression that peaked between 1 and 3 days and was detected up
      to 28 days after DNA administration. Transgene expression was independent of
      mouse gender, age and strain. Levels of expression from DNA in various isotonic
      solutions did not differ from levels obtained with DNA administered in water,
      suggesting that transfection is not dependent on damage to airway cells caused by
      a hypo-osmotic delivery vehicle. Pharmacokinetic studies using radiolabeled
      plasmid DNA showed that DNA was rapidly degraded, while higher levels of
      radioactivity were retained for longer duration following administration of
      cationic liposome-DNA complexes in the airway. Southern blot and PCR analysis
      confirmed that DNA complexed with DOTMA-DOPE was retained in the airways for a
      longer period. However, cationic liposomes DOTMA-DOPE (1:1) or DOTAP complexed
      with DNA, did not enhance expression over DNA alone. These results suggest that
      'naked' plasmid DNA should be included as a control in all studies on
      intratracheal gene delivery using nonviral systems.

PMID- 7584124
TI  - Complementation of defective leucine decarboxylation in fibroblasts from a maple
      syrup urine disease patient by retrovirus-mediated gene transfer.
AB  - Maple syrup urine disease (MSUD) is a genetic disease caused by a deficiency of
      branched-chain keto acid dehydrogenase, a mitochondrial multienzyme complex
      responsible for the decarboxylation of leucine, isoleucine and valine. The
      complex consists of three subunits (E1, E2, and E3) and mutations in any subunit
      result in MSUD. No satisfactory treatment for MSUD is currently available. Here
      we report the successful use of retroviral gene transfer to restore leucine
      decarboxylation activity in fibroblasts derived from a MSUD patient containing a
      mutation in the E2 subunit. A full-length human E2 cDNA was inserted into a
      retroviral vector (MFG) and a stable CRIP producer line was generated. The
      amphotropic virus was then used to transduce mutant human fibroblasts. In
      untransduced mutant cells, 1-14C leucine decarboxylation activity was less than
      2% that of the wild-type cells. Decarboxylation of 1-14C leucine in transduced
      mutant cells was restored to 93% of the wild-type level. Correct targeting of the
      expressed wild-type E2 protein to mitochondria was demonstrated by comparing the
      immunofluorescent pattern of E2 and a mitochondrial marker protein. Stable
      expression of enzyme activity has been obtained for at least 7 weeks. In contrast
      to most previous gene therapy attempts, which replace a single enzyme defect, the
      present results demonstrate complementation of a phenotype resulting from a gene
      defect whose product is a part of a multienzyme complex. Based on these results,
      studies can now be undertaken to investigate the feasibility of gene therapy to
      correct MSUD.

PMID- 7584127
TI  - Evaluation of retroviral vectors based on the gibbon ape leukemia virus.
AB  - The gibbon ape leukemia viruses (GaLVs) are primate-derived C-type retroviruses
      with a broad host range. Using an infectious, full-length clone of the GaLV SEATO
      strain, we have determined that this virus replicates efficiently in 13 of 17
      human cell lines tested. In fact, the SB lymphoblast cell line, while resistant
      to infection by wild-type amphotropic mouse leukemia virus (A-MLV), was infected
      by GaLV-SEATO. We constructed vectors containing GaLV components and compared the
      performance of genomes containing an enhancer and promoter derived either from
      the SEATO or SF strains of GaLV. The GaLV vector genomes were packaged in a
      Moloney (Mo)MLV core with either an A-MLV or GaLV SEATO envelope. We found that,
      in some cases, the vector genome appeared to be critical in obtaining optimal
      infection. For example, vectors with a GaLV SF-based genome infected the human
      HL60 cell line, whereas vectors with a GaLV SEATO-based genome did not. We also
      found that most, but not all, of the human cell lines tested were more
      susceptible to vectors packaged with the GaLV SEATO than A-MLV envelope. The
      source of the viral core was also important, in that some human cells appeared
      susceptible to infection only with GaLV genomes packaged in particles composed of
      a GaLV core and envelope. Our results show that GaLV-based packageable genomes
      can be expressed in target cells not efficiently infected by vectors containing
      MoMLV-based genomes. These results suggest that judicious combinations of
      retroviral genomes and structural components can significantly improve gene
      transfer into human cells.

PMID- 7584125
TI  - A recombinant adenoviral vector expressing a soluble form of VCAM-1 inhibits VCAM
      1/VLA-4 adhesion in transduced synoviocytes.
AB  - Intra-articular injection of recombinant adenovirus has been shown to be a
      feasible approach to the introduction of genetic reagents into synovial tissues
      in vivo. Rheumatoid arthritis (RA) is an autoimmune disorder characterized by the
      infiltration of lymphocytes and monocytes into inflamed synovium. It has been
      hypothesized that the recruitment of T lymphocytes/monocytes into sites of
      chronic inflammation is mediated by enhanced binding of very late antigen-4 (VLA
      4) to vascular cell adhesion molecule-1 (VCAM-1) expressed on microvascular
      endothelial cells. Additional evidence suggests that VLA-4 binding continues to
      be important within the inflamed synovial membrane, where it appears to play a
      role in T cell retention and activation. A feasible therapeutic strategy for RA
      could be to utilize a soluble congener of the VCAM-1 molecule to block VLA-4
      binding. In order to test this concept, a recombinant serotype Ad5 human
      adenovirus encoding a secreted form of VCAM-1 (Ad.CBsVCAM) was constructed. Human
      synoviocytes were readily infected in vitro with Ad.CBsVCAM, and sVCAM-1
      expression and processing were analyzed by immunoprecipitation studies. Secretion
      of transgenic sVCAM was identified by ELISA of tissue culture supernatants, and
      biological activity was demonstrated with cell adhesion assays. In vivo,
      transgenic sVCAM-1 expression was determined by immunohistochemical analysis and
      in situ hybridization of synovial tissue, and secretion of transgenic sVCAM-1 was
      demonstrated by ELISA of tidal knee lavage fluid. The results showed that
      recombinant adenovirus can mediate the expression of a biologically active sVCAM
      1 by synoviocytes in vivo and suggest that this strategy may be useful for
      inhibiting T lymphocyte retention and activation within rheumatoid synovium.

PMID- 7584126
TI  - Generation of recombinant adeno-associated virus (rAAV) from an adenoviral vector
      and functional reconstitution of the NADPH-oxidase.
AB  - The human parvovirus, adeno-associated virus-2 (AAV-2), has many attributes that
      recommend its use as a gene transfer vehicle, including a broad tissue tropism,
      the ability to integrate stably into the host genome, and efficient transduction
      of cells which proliferate slowly. However, application to human gene therapy is
      currently limited by existing methods for generation of recombinant AAV (rAAV),
      resulting in relatively low transducing titres. In an attempt to overcome some of
      these problems, we have developed a defective adenoviral vector which improves
      the efficiency of rAAV vector delivery to cells in which rAAV is propagated, and
      from which the rAAV genome can be efficiently rescued. A functional copy of the
      p47phox gene was successfully transferred to cell lines derived from patients
      with autosomal recessive chronic granulomatous disease (CGD) by rAAV recovered in
      this way, and function of the NADPH-oxidase was restored to levels which were
      stable for at least 8 weeks. This method for generation of rAAV, although still
      limited by the need for cotransfection of AAV Rep and Cap functions, may permit
      recovery of higher titre transducing stocks from cell lines in which these genes
      are stably incorporated, and significantly reduces the risk of contamination with
      wild-type adenovirus (wtAd).

PMID- 7584128
TI  - Local regression of breast tumors following intramammary ganciclovir
      administration in double transgenic mice expressing neu oncogene and herpes
      simplex virus thymidine kinase.
AB  - Females from a mouse lineage transgenic for the activated rat neu oncogene under
      the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR)
      all develop breast tumors with high reproducibility within the first 2-3 months
      of life. These animals were crossed with mice from a lineage transgenic for the
      herpes simplex virus thymidine kinase gene (HSVtk) under the control of its own
      promoter and polyoma enhancer. Double transgenic mice (for both neu and tk)
      developed breast neoplasias with the same kinetics as the neu-only mice. Tumor
      bearing double transgenic mice, treated intratumorally with the antiviral agent
      ganciclovir (GCV), showed an inhibiting effect on tumor growth. However, this
      effect was not seen either on GCV-treated neu-only transgenic mice or on saline
      injected controls. This suggests that tk-engineered breast tumors are susceptible
      to GCV administered locally, and implies that neu-mice could be a useful model
      for testing the effectiveness of HSVtk-bearing vectors followed by systemic GCV
      on breast cancer cells.

PMID- 7584129
TI  - Efficient gene delivery and expression in mammalian cells using DNA coupled with
      perfringolysin O.
AB  - Current non-viral DNA vectors for gene therapy are limited by low cellular
      transfection efficiencies and low levels of gene expression due to inefficient
      endosomal DNA release. We have used perfringolysin O (PFO), a membrane active
      bacterial protein, to deliver DNA into cells. PFO belongs to the so-called
      sulphydryl-activated family of membrane active bacterial proteins, which have
      been used to deliver small molecules and proteins into cells. PFO was
      incorporated into DNA complexes through a biotin-streptavidin bridge and the DNA
      PFO complexes were used to deliver the Escherichia coli beta-galactosidase gene
      into cells. High levels of gene expression were achieved in murine sol 8 myoblast
      cells using these DNA-PFO complexes. The level of gene expression correlated well
      with the content of PFO in the complexes. Under optimal conditions, 15-20% of the
      cells were stained blue with X-gal. Furthermore, the expression was independent
      of a receptor ligand. Thus, membrane active bacterial proteins may be an
      important tool for the future development of non-viral DNA delivery systems for
      gene therapy.

PMID- 7584130
TI  - Enhanced transduction efficiency of retroviral vectors coprecipitated with
      calcium phosphate.
AB  - Retroviral vectors are being used increasingly in clinical gene therapy protocols
      but low transduction frequencies are presenting a significant obstacle to
      progress. In this paper we report a simple method to enhance the efficiency of ex
      vivo retroviral gene transfer. Calcium chloride is added to the vector stock and
      calcium phosphate precipitates out of solution in complex with the retroviral
      vectors. When such coprecipitated vectors were used for gene transfer, the vector
      titres were increased at least five-fold and as much as 50-fold compared with the
      titres obtained in standard polybrene-enhanced infection protocols. Titre
      enhancement was not dependent on the starting concentration of vector, was
      equally effective for ecotropic and amphotropic vectors on a variety of mouse and
      human cells, and was not associated with any alteration in vector host range
      properties. The method may be of value to concentrate retroviral vectors and to
      enhance the efficiency of gene transfer in selected human gene therapy protocols.

PMID- 7584131
TI  - An altered peptide ligand mediates immune deviation and prevents autoimmune
      encephalomyelitis.
AB  - In experimental autoimmune encephalomyelitis (EAE) induced with myelin
      proteolipid protein (PLP) peptide 139-151, we have previously shown that the
      disease is mediated by Th1 cells, which recognize tryptophan 144 as the primary
      TCR contact point. Here we describe an altered peptide ligand (APL), generated by
      a single amino acid substitution (tryptophan to glutamine) at position 144
      (Q144), which inhibits the development of EAE induced with the native PLP 139-151
      peptide (W144). We show that the APL induces T cells that are cross-reactive with
      the native peptide and that these cells produce Th2 (IL-4 and IL-10) and Th0 (IFN
      gamma and IL-10) cytokines. Adoptive transfer of T cell lines generated with the
      APL confer protection from EAE. These data show that changing a single amino acid
      in an antigenic peptide can significantly influence T cell differentiation and
      suggest that immune deviation may be one of the mechanisms by which APLs can
      inhibit an autoimmune disease.

PMID- 7584132
TI  - Low avidity recognition of self-antigen by T cells permits escape from central
      tolerance.
AB  - The immunodominant epitope of myelin basic protein, Ac1-9, is encephalitogenic in
      H-2u mice. We have previously demonstrated that this epitope displays low
      affinity for I-Au and have suggested that the avidity of T cell recognition in
      the thymus may be compromised, enabling autoreactive T cells to escape self
      tolerance. We have addressed this hypothesis directly by constructing transgenic
      mice expressing an encephalitogenic T cell receptor (TCR). Parenteral
      administration of Ac1-9 had no discernable impact on developing thymocytes. In
      contrast, peptide analogs displaying far higher affinity for I-Au, provoked
      deletion of CD4+ CD8+ cells and transient down-regulation of the TCR by mature
      CD4+ CD8- thymocytes. The use of analogs of intermediate affinity permitted a
      margin of error to be defined for the induction of tolerance and confirmed that
      the affinity of Ac1-9 lies well below the critical threshold.

PMID- 7584133
TI  - Selective CD28pYMNM mutations implicate phosphatidylinositol 3-kinase in CD86
      CD28-mediated costimulation.
AB  - CD28 costimulatory signals are required for lymphokine production and T cell
      proliferation. CD28 signaling recruits the intracellular proteins PI 3-kinase,
      ITK, and GRB-2/SOS. PI 3-kinase and GRB-2/SOS bind the CD28 cytoplasmic pYMNM
      motif via SH2 domains. We generated CD28 pYMNM mutants and found that Y191
      mutation (Y191CD28F) disrupted both PI 3-kinase and GRB-2 binding, while M194
      mutation (M194CD28C) disrupted only PI 3-kinase binding. Both mutants still bound
      ITK. We have assessed the ability of these selective mutants to support IL-2
      production upon TCR zeta/CD3 ligation in the presence of CHO-CD86 (B7-2) cells.
      Both Y191CD28F and M194CD28C mutants failed to generate IL-2. These data directly
      implicate PI 3-kinase in CD28-mediated costimulation leading to IL-2 secretion.
      Wortmannin, an inhibitor of PI 3-kinase, induced cell apoptosis and as such was
      unsuitable for use in this study.

PMID- 7584134
TI  - TCR-associated zeta-Fc epsilon RI gamma heterodimers on CD4-CD8- NK1.1+ T cells
      selected by specific class I MHC antigen.
AB  - The origin of autoreactive CD4-CD8- T cells is largely unknown. In TCR transgenic
      (Tg) mice expressing the cognate class I MHC antigen, CD4-CD8- T cells differed
      depending on characteristics of Tg-TCR/antigen interaction. Tg-TCR/CD3lo CD4-CD8-
      T cells expressing the NK1.1 marker were observed only for a Tg-TCR whose
      stimulation by antigen was independent of CD8. Unlike normal T cells, which have
      essentially TCR-associated zeta homodimers, these cells had a high proportion of
      TCR-associated zeta-Fc epsilon RI gamma heterodimers. They were also
      characterized by an unusually high content of Fc epsilon RI gamma mRNA and low
      content of mRNA encoding CD3 epsilon, CD3 gamma, CD3 delta, and zeta. Based on
      their phenotype and selection requirements, it is proposed that CD4-CD8- thymic
      precursor cells can be driven along the CD4-CD8-NK1.1+ pathway following
      coreceptor-independent TCR signaling at an intrathymic stage when Fc epsilon RI
      gamma and CD3 components are coexpressed.

PMID- 7584135
TI  - The role of short homology repeats and TdT in generation of the invariant gamma
      delta antigen receptor repertoire in the fetal thymus.
AB  - Fetal thymic and adult epithelial V gamma 3+ and V gamma 4+ T cells express gamma
      delta antigen receptors (TCR) with invariant junctions lacking N nucleotides.
      Using transgenic recombination substrates, we show that di- or trinucleotide
      repeats, either in the coding region or in P elements, have strong effects on the
      site of recombination. In other mice bearing a terminal deoxynucleotidyl
      transferase (TdT) transgene under the control of the CD2 promoter, we found that
      the frequency of canonical junctions was markedly reduced with a concomitant
      increase in in-frame noncanonical junctions with N nucleotides. Together, our
      results show that short homology repeats direct the site of rearrangement and
      thus play a critical role in the generation of gamma delta T cell receptor
      canonical junctions. Increased TdT activity in V gamma 3+ T cells has a
      inhibitory effect on junctional homogeneity in these cells.

PMID- 7584136
TI  - Allelic exclusion of mouse T cell receptor alpha chains occurs at the time of
      thymocyte TCR up-regulation.
AB  - We report a detailed analysis of TCR V alpha and V beta chain expression on
      immature versus mature thymocytes of normal, TCR beta-transgenic, and TCR alpha
      hemizygous mice. Chain pairing between TCR V alpha and V beta chains is random on
      immature thymocytes, but individual chain pairs are selected in mature
      thymocytes. This indicates that V alpha-V beta chain pairing preferences are
      determined during thymic selection, and not as a result of structural
      constraints. Dual V alpha chain expression is found frequently on immature, but
      not mature thymocytes. It is not found in TCR alpha-hemizygous mice, showing that
      cell surface expression of dual alpha chains is caused by lack of allelic
      exclusion in immature thymocytes. Down-regulation of one of the alpha chains
      occurs concurrently with differentiation from TCRlo, CD69- to TCRhi, CD69+
      phenotype, suggesting that it is associated with positive selection of the
      functional TCR.

PMID- 7584139
TI  - Mannose binding protein (MBP) enhances mononuclear phagocyte function via a
      receptor that contains the 126,000 M(r) component of the C1q receptor.
AB  - Mannose-binding protein (MBP), C1q, the recognition component of the classical
      complement pathway, and pulmonary surfactant protein A (SP-A) are members of a
      family of molecules containing a collagen-like sequence contiguous with a
      noncollagen-like sequence, and usually having the properties of a lectin. C1q and
      SP-A have been shown to enhance monocyte FcR- and CR1-mediated phagocytosis,
      suggesting that the common structural features of the collagen-like domains may
      provide a basis for this immunologically important function. Results presented
      here demonstrate that MBP also enhanced FcR-mediated phagocytosis by both
      monocytes and macrophages, and stimulated CR1-mediated phagocytosis in human
      culture-derived macrophages and in phorbol ester-activated monocytes.
      Furthermore, a monoclonal antibody that recognizes a 126,000 M(r) cell surface
      protein and inhibits C1q-enhanced phagocytosis, inhibited the MBP-mediated
      enhancement of phagocytosis. Thus, the receptors that mediate the enhancement of
      phagocytosis by MBP and C1q share at least one critical functional component, the
      126,000 M(r) ClqRP.

PMID- 7584137
TI  - Human T, B, natural killer, and dendritic cells arise from a common bone marrow
      progenitor cell subset.
AB  - The early stages of lymphoid cell formation were studied by testing the
      differentiative potential of phenotypically defined subsets of CD34+ bone marrow
      cells. A subpopulation of CD34+ Lin- CD45RA+ cells expressing CD10 was isolated
      by flow cytometry. Such cells are CD38+, HLA-DR+, do not express significant
      levels of Thy-1 and c-kit, lack erythroid, myeloid, megakaryocytic potential, and
      give rise only to lymphoid T, B, natural killer (NK), and dendritic cells (DC) in
      kinetics and titration experiments. Limiting dilution analysis demonstrates the
      existence of multipotential B/NK/DC progenitor clones in the CD34hi Lin-CD10+
      adult bone marrow cell population. Thus, nonprimitive progenitors for lymphoid
      cells and for DCs can be distinct from those of myeloid, megakaryocytic, and
      erythroid cells, implying that the DC lineage is developmentally more closely
      related to the lymphoid lineage than to the myeloid lineage. This study provides
      new insights into the organization and development of the human lympho
      hematopoietic system.

PMID- 7584138
TI  - Resident bone marrow macrophages produce type 1 interferons that can selectively
      inhibit interleukin-7-driven growth of B lineage cells.
AB  - Type 1 interferons alpha and beta are found to be potent inhibitors of IL-7
      induced growth of early B lineage cells, while having no effect on cell growth
      induced by IL-2, IL-3, IL-4, or autogenous factors. The combination of IL-7 and
      interferons alpha/beta induces bcl-2 down-regulation and cell death by apoptosis.
      These conclusions were derived initially from experiments employing exogenous
      cytokines, but functional type 1 interferons are also shown to be produced by
      resident bone marrow macrophages. As physiological modulators of IL-7-driven
      proliferation and cell survival, interferons alpha/beta may cooperate with other
      homeostatic factors to maintain the balanced production of normal B lineage
      cells.

PMID- 7584141
TI  - Anatomy of autoantibody production: dominant localization of antibody-producing
      cells to T cell zones in Fas-deficient mice.
AB  - The goal of this study was to examine the in vivo site of autoantibody production
      in normal and autoimmune-prone mice. B cells were identified in tissue sections
      with IgM- and IgG2a-specific riboprobes that readily distinguished resting cells
      from antibody-forming cells (AFC). In normal mice, the few identifiable IgG2a
      secreting cells were found in the red pulp. By contrast, in Ipr mice exceedingly
      high numbers of IgG2a and autoantibody-producing cells were found deep within the
      T cell-rich periarteriolar lymphoid sheaths (PALS). This unusual anatomic
      location of autoantibody-secreting B cells is unique to Fas dysregulated strains,
      since IgG2-producing cells in MRL/+ and (SWR x NZB)F1 mice were found
      predominantly in the red pulp or outer PALS, similar to normal mice. Furthermore,
      analysis of spleens from Ipr and non-Ipr anti-DNA immunoglobulin transgenic mice
      revealed dramatic accumulation of Tg+ cells in the inner PALS only in Ipr mice.
      These data suggest that in the absence of Fas, autoreactive B cells accumulate in
      T cell-rich zones, and this anatomic feature may contribute to autoantibody
      production.

PMID- 7584140
TI  - Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma
      delta T cells.
AB  - Human V gamma 2V delta 2+ T cells recognize mycobacterial nonpeptide antigens,
      such as isopentenyl pyrophosphate, and their synthetic analogs, such as monoethyl
      phosphate, through a TCR-dependent process. Here, we examine the presentation of
      these antigens. V gamma 2V delta 2+ T cells recognized secreted prenyl
      pyrophosphate antigens in the absence of other accessory cells but, under such
      conditions, required T cell-T cell contact. Recognition required neither the
      expression of classical MHC class I, MHC class II, or CD1a, CD1b, and CD1c
      molecules, nor MHC class I or class II peptide loading pathways. Fixed accessory
      cells also presented the prenyl pyrophosphate antigens to gamma delta T cells.
      Thus, in contrast with the presentation of conventional peptide antigens, protein
      antigens, and superantigens to alpha beta T cells, prenyl pyrophosphate antigens
      are presented to gamma delta T cells through a novel extracellular pathway that
      does not require antigen uptake, antigen processing, or MHC class I or class II
      expression. This pathway allows for the rapid recognition of bacteria by gamma
      delta T cells and suggests that gamma delta T cells play a role in the early
      response to bacterial infection.

PMID- 7584142
TI  - Interleukin-2 receptor alpha chain regulates the size and content of the
      peripheral lymphoid compartment.
AB  - Interleukin-2 receptor alpha chain (IL-2R alpha) expression occurs at specific
      stages of early T and B lymphocyte development and is induced upon activation of
      mature lymphocytes. Young mice that lack IL-2R alpha have phenotypically normal
      development of T and B cells. However, as adults, these mice develop massive
      enlargement of peripheral lymphoid organs associated with polyclonal T and B cell
      expansion, which, for T cells, is correlated with impaired activation-induced
      cell death in vivo. Older IL-2R alpha-deficient mice also develop autoimmune
      disorders, including hemolytic anemia and inflammatory bowel disease. Thus, IL-2R
      alpha is essential for regulation of both the size and content of the peripheral
      lymphoid compartment, probably by influencing the balance between clonal
      expansion and cell death following lymphocyte activation.

PMID- 7584143
TI  - New insights into V(D)J recombination and its role in the evolution of the immune
      system.

PMID- 7584144
TI  - Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue
      destruction, revealing a critical negative regulatory role of CTLA-4.
AB  - The B7-CD28/CTLA-4 costimulatory pathway can provide a signal pivotal for T cell
      activation. Signaling through this pathway is complex due to the presence of two
      B7 family members, B7-1 and B7-2, and two counterreceptors, CD28 and CTLA-4.
      Studies with anti-CTLA-4 monoclonal antibodies have suggested both positive and
      negative roles for CTLA-4 in T cell activation. To elucidate the in vivo function
      of CTLA-4, we generated CTLA-4-deficient mice. These mice rapidly develop
      lymphoproliferative disease with multiorgan lymphocytic infiltration and tissue
      destruction, with particularly severe myocarditis and pancreatitis, and die by 3
      4 weeks of age. The phenotype of the CTLA-4-deficient mouse strain is supported
      by studies that have suggested a negative role for CTLA-4 in T cell activation.
      The severe phenotype of mice lacking CTLA-4 implies a critical role for CTLA-4 in
      down-regulating T cell activation and maintaining immunologic homeostasis. In the
      absence of CTLA-4, peripheral T cells are activated, can spontaneously
      proliferate, and may mediate lethal tissue injury.

PMID- 7584145
TI  - Impaired proliferation of peripheral B cells and indication of autoimmune disease
      in lyn-deficient mice.
AB  - The Src family protein-tyrosine kinase Lyn associates physically with the BCR and
      has been suggested to play an important role in BCR-mediated signaling. Studies
      with lyn-/- mice showed that the number of B cells decreased by half in their
      peripheral tissues. In addition, these B cells do not respond normally to a
      number of stimuli, including BCR cross-linking and CD40 ligand. Induction of
      tyrosine phosphorylation on a variety of cellular proteins, such as Vav, Cbl, and
      HS1, upon BCR cross-linking was also abolished in these B cells. Despite the
      impaired BCR-mediated signaling, concentrations of IgM and IgA in sera were
      remarkably elevated, and production of autoantibodies was detected in lyn-/-
      mice. Histological study showed splenomegaly and enlargement of lymph nodes that
      became evident with age in the mutant mice. The spleen contained significant
      number of plasma cells as well as unusual lymphoblast-like cells carrying Mac1
      antigen and cytoplasmic IgM. These cells spontaneously secreted a large amount of
      IgM in vitro. Finally, significant number of lyn-/- mice show glomerulonephritis,
      an indication of autoimmune disease. From these data, we conclude that Lyn plays
      a role in signal transduction for not only clonal expansion and terminal
      differentiation of peripheral B cells but also elimination of autoreactive B
      cells.

PMID- 7584148
TI  - The MHC class I homolog encoded by human cytomegalovirus binds endogenous
      peptides.
AB  - The ability of a human cytomegalovirus-encoded homolog of MHC class I molecules
      to serve as a peptide receptor was investigated. Sequencing of peptide material
      eluted from the purified viral protein revealed a mixture of endogenous peptides
      with characteristics similar to those eluted from conventional class I molecules,
      that is, anchor residues, and a predominance of short peptides derived from
      cytoplasmic proteins. The possible function(s) of this viral MHC homolog are
      discussed in light of the finding that it binds endogenous peptides.

PMID- 7584146
TI  - The MHC class II molecule H2-M is targeted to an endosomal compartment by a
      tyrosine-based targeting motif.
AB  - The nonpolymorphic human class II molecule HLA-DM (DM) has been found to play a
      key role in antigen presentation by MHC class II molecules. HLA-DM and its murine
      equivalent H2-M are located intracellularly and are absent from the cell surface.
      In transfected HeLa cells, H2-M was transported to an endosomal compartment in
      the absence of invariant chain. A tyrosine-based targeting motif in the
      cytoplasmic tail of H2-M beta was responsible for the endosomal location and, if
      this tyrosine was mutated, H2-M accumulated at the cell surface. In the presence
      of invariant chain the mutated H2-M was redistributed to endosomes. The targeting
      motif of H2-M appeared not to be crucial for efficient peptide loading of class
      II, but if the invariant chain targeting motif also was removed, peptide loading
      decreased drastically. Thus, the targeting motif of H2-M appears to be
      supplementary, rather than essential for class II-peptide association.

PMID- 7584147
TI  - Evidence that the antigen receptors of cytotoxic T lymphocytes interact with a
      common recognition pattern on the H-2Kb molecule.
AB  - Recognition of class I MHC antigens involves interaction between TCRs of
      cytotoxic T lymphocytes (CTL) and the two alpha helices of MHC molecules. Using a
      combined panel of H-2Kb mutants selected by either a CTL clone or MAbs, we have
      shown evidence that the TCRs of 59 Kb-specific CTL clones shared a common binding
      pattern on the H-2Kb molecule. Mutations of amino acid residues at the C-terminal
      regions, but not the N-terminal regions, of the alpha helices abrogated the
      recognition by the majority of the clones. The data suggests that TCRs
      predominantly recognize the class I MHC molecule with an orientation that is
      parallel to the beta-pleated strands and diagonal to the alpha helices.

PMID- 7584149
TI  - The membrane-bound and soluble forms of HLA-G bind identical sets of endogenous
      peptides but differ with respect to TAP association.
AB  - The class Ib antigen HLA-G is expressed as a membrane-bound protein like
      classical class Ia molecules (M.HLA-G) but, unlike typical class I, is also
      expressed as a soluble protein (S.HLA-G) with a unique C terminus. Our results
      show that, similar to classical class I proteins, the membrane-bound form of HLA
      G associated with TAP, as evidenced by the ability to immunoprecipitate HLA-G
      class I heavy chain with TAP antisera. In contrast, the soluble G protein did not
      appear to associate with TAP in the same manner, since similar
      immunoprecipitation experiments failed to detect soluble G complex. A detailed
      analysis of peptides bound to the soluble and membrane HLA-G proteins expressed
      in the B lymphoblastoid cell line 721.221 showed that, like class Ia complexes,
      both HLA-G proteins consist of heavy and light chains complexed with nonameric
      peptides in a 1:1:1 ratio. The two proteins bind essentially the same set of
      peptides, which are derived from a variety of intracellular proteins and define a
      peptide motif for HLA-G. The peptides contain Leu at the C terminus and Pro or
      small hydrophobic amino acids in position 3 followed by Pro or Gly in position 4.
      The complexity of the bound peptides is lower than that found for some class Ia
      complexes, but is more similar to class Ia than to the limited repertoire of some
      murine class Ib molecules.

PMID- 7584151
TI  - V-D-J rearrangements at the T cell receptor delta locus in mouse thymocytes of
      the alpha beta lineage.
AB  - The T cell receptor (TCR) delta locus lies within the TCR alpha locus and is
      excised from the chromosome by V alpha-J alpha rearrangement. We show here that
      delta sequences persist in a large fraction of the DNA from mature CD4+CD8- alpha
      beta+ mouse thymocytes. Virtually all delta loci in these cells are rearranged
      and present in extrachromosomal DNA. In immature alpha beta lineage thymocytes
      (CD3-/loCD4+CD8+) and in CD4+CD8- alpha beta+ thymocytes expressing a transgene
      encoded alpha beta receptor, rearranged delta genes are present both in
      chromosomal and extrachromosomal DNA. Thus, contrary to earlier proposals,
      commitment to the alpha beta lineage does not require recombinational silencing
      of the delta locus or its deletion by a site-specific mechanism prior to V alpha
      J alpha rearrangement.

PMID- 7584152
TI  - Tyrosine-phosphorylated T cell receptor zeta chain associates with the actin
      cytoskeleton upon activation of mature T lymphocytes.
AB  - The multichain T cell antigen receptor (TCR) is composed of an antigen binding
      (alpha/beta) domain and associated signal-transducing complexes, the CD3 (gamma,
      delta, and epsilon) and the zeta chains. The zeta chain (TCR zeta) plays a key
      role in signal transduction. We show here that TCR ligation induces association
      of tyrosine-phosphorylated TCR zeta with the detergent-insoluble cell fraction.
      The microfilament poison, cytochalasin D, disrupts this association and enhances
      the coprecipitation of actin with TCR zeta after receptor ligation. This
      microfilament association is specific to TCR-associated polypeptides containing
      at least one intact immunoreceptor tyrosine-based activation motif (ITAM).
      Mapping studies using transfectants and chimeric TCR zeta chain constructs
      suggest that the third ITAM is necessary and sufficient for association, if the
      distal tyrosine is intact. This cytoskeletal association is directly correlated
      with IL-2 production, and ligation of TCR on immature thymocytes does not induce
      TCR zeta-cytoskeleton association. These data thus provide direct evidence of a
      developmentally regulated activation-dependent interaction between a lymphocyte
      antigen receptor and the actin cytoskeleton.

PMID- 7584150
TI  - Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional
      immunoglobulin heavy chain rearrangement.
AB  - Two waves of immunoglobulin gene rearrangements, first of the heavy, then of the
      light chain chain gene loci form functional immunoglobulin genes during B cell
      development. In mouse bone marrow the differential surface expression of B220
      (CD45R), c-kit, CD25, and surrogate light chain as well as the cell cycle status
      allows FACS separation of the cells in which these two waves of rearrangements
      occur. The gene products of two recombination activating genes, RAG1 and RAG2 are
      crucial for this rearrangement process. Here, we show that the expression of the
      RAG genes is twice up- and down-regulated, at the transcriptional level for RAG1
      and RAG2, and at the postranscriptional level for RAG2 protein. Expression levels
      are high in D-->JH and VH-->DJH rearranging proB and preB-I cells, low in preB
      cells expressing the preB cell receptor on the cell surface, and high again in VL
      ->JL rearranging small preB-II cells. In immature B cells expressing on the cell
      surface RAG1 and RAG2 mRNA is down-regulated, whereas RAG2 protein levels are
      maintained. Down-regulation of RAG1 and RAG2 gene expression after productive
      rearrangement at one heavy chain allele might be part of the mechanisms that
      prevent further rearrangements at the other allele.

PMID- 7584153
TI  - The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc
      gamma RIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation.
AB  - The cell-triggering properties of BCR, TCR and FcR depend on structurally related
      immunoreceptor tyrosine-based activation motifs (ITAMs). Fc gamma RIIB have no
      ITAM and do not trigger cell activation. When coaggregated to BCR, they inhibit B
      cell activation. We show here that, when coaggregated to these receptors, Fc
      gamma RIIB inhibit Fc epsilon RI-, Fc gamma RIIA-, and TCR-dependent cell
      activation. Inhibition also affected cell activation by single ITAMs, in isolated
      FcR or TCR subunits. The same tyrosine-based inhibitory motif (ITIM), which is
      highly conserved in murine and human Fc gamma RIIB and that was previously shown
      to inhibit BCR-dependent B cell activation, was required to regulate TCR- and FcR
      dependent cell activation. Our findings endow Fc gamma RIIB, and thus IgG
      antibodies, with general immunoregulatory properties susceptible to act on all
      ITAM-containing receptors.

PMID- 7584154
TI  - A targeted glucocorticoid receptor antisense transgene increases thymocyte
      apoptosis and alters thymocyte development.
AB  - The exquisite sensitivity of thymocytes to steroid-induced apoptosis, the
      steroidogenic potential of thymic epithelial cells, and the ability of steroid
      synthesis inhibitors to enhance antigen-specific deletion of thymocytes in fetal
      thymic organ cultures suggest a role for glucocorticoids in thymocyte
      development. To address this further, transgenic mice that express antisense
      transcripts to the glucocorticoid receptor (GR) specifically in immature
      thymocytes were generated. The consequent hyporesponsiveness of thymocytes to
      glucocorticoids was accompanied by a reduction in thymic size, primarily owing to
      a decrease in the number of CD4+CD8+ cells. While an enhanced susceptibility to T
      cell receptor (TCR)-mediated apoptosis appeared to be partially responsible for
      this reduction, thymocyte loss could also be detected before thymocytes
      progressed to the CD4+CD8+ TCR alpha beta-expressing stage. These results suggest
      that glucocorticoids are necessary for survival and maturation of thymocytes, and
      are consistent with a role for steroids in both the transition from CD4-CD8- to
      CD4+CD8+ cells and the survival of CD4+CD8+ cells stimulated via the TCR.

PMID- 7584155
TI  - Tissue-specific targeting of cytokine unresponsiveness in transgenic mice.
AB  - The ubiquitous cellular distribution of certain cytokine receptors has hampered
      attempts to define the physiologically important cell-specific functions of
      cytokines in vivo. Herein, we report the generation of transgenic mice that
      express a dominant-negative IFN gamma receptor alpha chain mutant under the
      control of either the human lysozyme promoter or the murine lck proximal
      promoter, which display tissue-specific unresponsiveness in the macrophage or T
      cell compartments, respectively, to the pleiotropic cytokine, IFN gamma. We
      utilize these mice to identify previously undefined cellular targets of IFN gamma
      action in the development of a murine antimicrobial response and the mixed
      lymphocyte reaction. Moreover, we identify the macrophage as a critical
      responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T
      helper subset development. These studies thus represent a novel approach to
      studying the cell-specific actions of an endogenously produced pleiotropic
      cytokine in vivo.

PMID- 7584156
TI  - Effect of amylase treatment on the consistency of cooked, fermented oat bran
      porridge.
AB  - Oat bran porridges were cooked and fermented at 5, 10, 15, and 20% solids (as is
      basis). Cooking was carried out on gas stove and viscograph. Supplementation with
      malt flour at 0.1, 0.25, 0.5, 0.75, and 1%. Cooked oat bran porridge was
      inoculated with fresh yoghurt and fermented 18 h overnight in an incubator at 42
      degrees C. Falling number values were made to estimate the effects of amylase
      treatments by addition of malt flour on oat bran slurry when heated in an aqueous
      suspension. Pasting properties were observed with the viscograph and consistency
      measurements were made with Bostwick consistometer. The falling number method was
      not suitable for consistency measurements due to wide variations in values
      obtained. Enzymatic additions reduced the consistency of porridge with an
      increase in flowability during measurements. The peak heights obtained from the
      viscograms reduced proportionally with an increase in malt flour supplementation.
      The desirability of a product with higher energy values and a sufficiently low
      consistency that is spoonable was possible with cooked, fermented oat bran
      porridge.

PMID- 7584157
TI  - Studies on the underexploited legumes, Indigofera linifolia and Sesbania
      bispinosa: nutrient composition and antinutritional factors.
AB  - The nutrient composition and antinutritional factors of two Indian tribal pulses,
      Indigofera linifolia (L.f)Retz. and Sesbania bispinosa (Jacq.) W.F. Wight, were
      determined. The mature seeds contained 296.6-321.2 g kg-1 crude protein, 47.2
      64.2 g kg-1 crude lipid, 56.7-72 g kg-1 crude fiber, 27.6-31.9 g kg-1 ash and
      531.3-550.6 g kg-1 carbohydrates. The seeds of Indigofera linifolia were rich in
      K, Ca, Mn and Cu, whereas Sesbania bispinosa were rich in P and Zn. While
      albumins and globulins constituted the major proportion of seed proteins in
      Indigofera linifolia, globulins and glutelins formed the major bulk of seed
      proteins in Sesbania bispinosa. Seed lipids of both legumes contained a large
      proportion of unsaturated fatty acids with linoleic acid as the predominant one.
      These two pulses contained adequate levels of all the essential amino acids
      except sulpho-amino acids in total seed proteins and globulin fraction of
      Sesbania bispinosa. The in vitro protein digestibility of the raw seeds of
      Indigofera linifolia and Sesbania bispinosa were found to be 74.15% and 66.71%
      and cooked seeds 81.4% and 76.8%, respectively. Antinutritional factors such as
      total free phenolics, tannins, phytic acid, hydrogen cyanide, trypsin inhibitor
      and phytohaemagglutinating activities were also analysed.

PMID- 7584159
TI  - Nutritional evaluation of desi and kabuli chickpeas and their products commonly
      consumed in Pakistan.
AB  - Physicochemical and nutritional quality of five improved cultivars of desi and
      kabuli chickpeas and their products were studied. The kabuli chickpea had larger
      seed (26 g/100 seeds) than desi type (21 g/100 seeds). The hydration capacity per
      seed of desi (0.16 g) was lower than kabuli type (0.26 g). A positive correlation
      (r = 0.87) between seed weight and hydration capacity was observed. The mean
      cooking time of dry desi vs kabuli seed (124.5 vs 113.8 min) was reduced to 37.5
      vs 32.8 min and to 28.8 vs 22.5 min when soaked overnight in water and in 0.5%
      solution of sodium bicarbonate respectively. The mean value of protein (25.4 vs
      24.4%), fat (3.7 vs 5.1%), carbohydrate (47.4 vs 55%), crude fibre (11.2 vs
      3.9%), ash (3.2 vs 2.8%) and caloric value (327 vs 365 kcal/100 g) were for desi
      vs kabuli chickpeas respectively. There was no difference in the essential amino
      acid contents and in chemical scores of desi (65) and kabuli (67) chickpeas. The
      order of limiting amino acid was methionine+cystine, threonine and valine in both
      types. The chickpeas products contained 8.9-21.1% protein (N x 6.25), 3.1-21.8%
      fat, 53.4-75.9% carbohydrate, 1.6-11.1% crude fibre, 1.2-5.9% ash, 226-360mg Ca,
      126-315 mg P, 3.8-8.2 mg Fe, 1.8-5.4 mg Zn, 1.5-5.4 mg Mn, 0.6-1.1 mg Cu and 370
      490 kcal per 100 g. All chickpea products provided 7-23%, 7-40% and 52-78% of the
      total calories from protein, fat and carbohydrates respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584158
TI  - Fatty acid composition of the milk of well-nourished Sudanese women.
AB  - The fatty acid (FA) composition of samples of breast milk obtained from well
      nourished Sudanese women was determined by capillary gas chromatography.
      Saturated fatty acids (SFA) constituted 46%, monoenoic acids (MONOENE) 33% and
      polyunsaturated fatty acids (PUFA) accounted for 21% of total fatty acids. The
      mean value (18.28%) of the essential fatty acid linoleic acid was comparable to
      the levels reported for well-nourished mothers from industrialised countries. The
      proportions of fatty acids synthesised de novo in the mammary gland (10:0, 12:0,
      14:0) were less than expected from published studies of mothers consuming low fat
      diet averaging 17.4%. The amount of 22:6 n-3 which is synthesised from 18:3 n-3
      and also taken up by consumption of fish were found to be low. The possible
      nutritional implications of the low n-3 fatty acids for the infants should
      therefore be investigated.

PMID- 7584160
TI  - Effect of Japanese mint (Mentha arvensis) oil as fumigant on stored sorghum:
      physical characteristics, sensory quality and germination.
AB  - The Japanese mint (Mentha arvensis) oil (JMO) was effective as fumigant against
      Sitophilus oryzae in sorghum (Sorghum bicolor). The observations on the effect of
      JMO treatment at a dose of 166.6 microliters/l of space to grains stored for 3
      months in desiccators at 28 +/- 5 degrees C showed non significant (P
      approximately 0.05) effect on grain hardness, grain density and per cent water
      absorption. The cooking quality evaluated in terms of cooking time required for
      boiling of grains was also not significantly affected. The JMO treated samples of
      boiled sorghum scored significantly lower values for sensory quality
      characteristics viz. taste, aroma and overall acceptability compared to untreated
      samples. No effect of JMO on seed germination was observed. As sensory quality is
      lowered by use of JMO, the technique can only be recommended for seed sorghum
      preservation, not food.

PMID- 7584161
TI  - Comparative determination of ascorbic acid in bass (Morone lebrax) liver by HPLC
      and DNPH methods.
AB  - A reverse-phase high pressure liquid chromatographic technique (RP-HPLC) was
      developed for the analysis of ascorbic acid in bass liver. Ascorbic acid was
      extracted from bass liver and simultaneously assayed by RP-HPLC. The results were
      compared to the Dinitrophenylhydrazine (DNPH) method now in use. Recovery studies
      showed about 97% by the HPLC method compared to about 96% by the DNPH method.
      There was no statistically significant difference found in the values obtained
      from the two methods. The HPLC method described here is considered the preferred
      method both in terms of a shorter analysis time and greater sensitivity.

PMID- 7584162
TI  - An evaluation of a project to improve child nutrition in Tanzania.
AB  - Dietary bulk has been cited as an important factor influencing the nutritional
      intake of young children in developing countries. In Tanzania, a potential
      solution to the problem of dietary bulk in weaning foods, has been the promotion
      of 'kimea' or 'power flour' which is a cereal grain that has been sprouted
      (germinated). Flour made from this germinated grain contains amylase and has a
      thinning effect when added in small quantities to thick porridge thus allowing
      small children to consume a greater quantity of porridge. Alternatively, the
      effect of adding kimea to porridge can be seen as improving energy density
      because more flour can be added to the mixture whilst the same consistency is
      maintained. The frequency of use of kimea and mothers' perceptions about its
      value for young child feeding were evaluated in eight villages of Kyela district,
      Mbeya region, Tanzania. In four villages kimea had been promoted (project
      villages) and in the other four villages there had been no special programme of
      promotion (nonproject). A total of 131 mothers attending MCH clinics and 37
      dispensary staff were interviewed. Forty two per cent of project village mothers
      and 18% of nonproject village mothers had heard about the use of kimea for young
      child feeding but only 45% of these mothers used kimea when preparing porridge
      for their young children. Reasons for low adoption rates are discussed. Thirty
      seven per cent of mothers who had heard about kimea were unable to describe
      correctly how to use it to thin porridge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584163
TI  - The effects of processing on the availability of lysine in kenkey, a Ghanaian
      fermented maize food.
AB  - The effects of processing steps such as soaking, fermentation, cooking and drying
      on the availability of lysine in kenkey were investigated. Soaking increased
      lysine availability by 21% and 22% for maize and maize-cowpea mixtures,
      respectively. Cooking of soaked samples further improved lysine availability by
      68% and 31% for maize and maize-cowpea mixtures, respectively. Further
      significant improvements in lysine availability were effected by fermentation and
      cooking and values of 3.42 and 4.43 g/16 g N were recorded, respectively for
      maize and maize-cowpea doughs fermented for 4 days and cooked for 3 h. Cabinet
      drying had no significant effect on lysine availability, but drum drying of
      fermented maize and maize-cowpea doughs significantly lowered lysine availability
      in the resulting kenkey. A 1:1 mixture of cabinet and drum dried flours gave a
      product with higher available lysine content than the drum dried flour.

PMID- 7584166
TI  - Studies on the baking properties of non-wheat flours--I. Breadfruit (Artocarpus
      artilis).
AB  - The possibility of producing bread from wheat (WF)/Breadfruit (BF), composite
      flour has been examined. Wheat flour was supplemented with up to 50% breadfruit
      flour. Chemical analysis of the breadfruit flour indicated a high starch content
      (80.9 +/- 0.9%), a fairly high crude fibre and ash contents (1.6 +/- 0.3; 4.2 +/-
      0.3%) respectively and a low protein content (4.0 +/- 0.5%). Brabender amylograph
      pasting viscosity of the various flour and flour blends indicated that apart from
      the 100% WF, 10% BF/WF blends recorded the best pasting characteristics in terms
      of the starch stability, gelatinization index and set back values. While the 100%
      BF exhibited the poorest pasting characteristics. Physical characteristics
      indicated that only 100% WF and 10% BF/WF were free of cracks and crumbliness,
      20% and 30% BF/WF had slight cracks, while others are dense and highly cracked.
      This was reflected on the panellist judgment during sensory evaluation. There was
      no significant difference at P < 0.05 between the control (100% WF) and the
      composite bread samples up to 30% level of breadfruit flour. Others differed
      significantly.

PMID- 7584165
TI  - Alteration of circulating micronutrients with overt and occult infections in
      anaemic Guatemalan preschool children.
AB  - Clinical and laboratory data to define conditions of apparent health, localised
      infection or inapparent infection were available for 74 anaemic Guatemalan
      preschool children in the baseline phase of a clinical trial of the effect of
      iron and vitamin A on haematological status to be correlated with serum levels of
      four circulating micronutrients--iron, zinc, copper and retinol--known to be
      influenced by activation of the acute-phase reaction. Upon enrolment, only 29.7%
      of the children were free of all evidence of infection, 36.5% had one or more
      localised conditions detected on clinical examination, and 33.8% had an elevated
      white cell count and/or sedimentation rate, without localising features. These
      were classified as 'inapparent infections'. With respect to the healthy children,
      levels of iron, zinc, and retinol declined and copper generally increased in the
      four categories of clinical infections (acute respiratory infection, dermal
      infections, conjunctivitis, and 'other') but were also displaced in inapparent
      infections. Some activation of the acute-phase response in anaemic children may
      occur in the absence of clinical findings. Care must be taken in interpreting
      circulating micronutrient levels in relation to nutritional status in such
      population.

PMID- 7584164
TI  - Maternal nutritional status may be stressed by seasonal fluctuations in food
      availability: evidence from rural women in Kenya.
AB  - The effect of seasonal changes in household food availability on the dietary
      intakes and the nutritional status of 24 lactating women from smallholder rural
      households in Nakuru district Kenya, were investigated over a 15-month period in
      1992/93 agricultural cycle. Dietary intakes and body weights were measured on
      monthly basis. Significant seasonal differences were found in intakes of calcium,
      vitamin A, vitamin C, riboflavin, and niacin respectively (P < 0.01), as well as
      in the intake of protein, iron, and thiamin (P < 0.05), but not with energy and
      fat intake. Large interseasonal weight losses of 5.6 kg (about 9%) at the rate of
      1.1 kg/month, were observed between baseline measurements and the peak of the
      lean months when the energy intakes were 36.7 kcal/kg/day and protein at 1.1
      g/kg/day. About 50% of the lost weight (2.8 kg) were recovered during the harvest
      months of January and February, when energy intakes improved to 41.0 kcal/kg/day,
      and protein to 1.2 g/kg/day. However, further weight losses of 1.6 kg or 0.5
      kg/month occurred in the immediate postharvest months between March and June.
      While much of the weight loss may have been due to reduced energy intake during
      periods of food scarcity, part of the lost weight may have been due to increased
      energy requirement as a result of lactation and to increased physical activities.
      Further investigations are recommended.

PMID- 7584167
TI  - The use of high-phosphorus supplements to inhibit dental enamel demineralisation
      by ice lollies.
AB  - Five new formulations of water ice lollies with a high-phosphorus (low Ca)
      supplementation ratio were tested for their erosiveness of dental enamel or
      hydroxylapatite in vitro. Compared with the basic unsupplemented lolly, all five
      formulations that had been prepared with additional calcium and phosphorus, but
      in a low Ca/P ratio, as potential inhibitors of demineralisation, were associated
      with significantly less attack on dental mineral, as measured by the dissolution
      of calcium and phosphorus.

PMID- 7584168
TI  - The use of sugar as a vehicle for iodine fortification in endemic iodine
      deficiency.
AB  - The use of sugar as a vehicle for iodine supplementation was explored in a study
      of iodine deficiency in the Sudan. A survey of sugar consumption was conducted
      and established a widespread and uniform intake of sugar in all ages with no
      differences among socio-economic groups. The daily intake among adults varied
      from 48 g to 78 g as examined in five different geographical areas in the
      country. Iodinated sugar was produced by addition to sugar solution prior to
      crystallisation in an evapocrystallizer or sprayed on the conveyor of cured sugar
      before it entered the dryers. Subsequently, the iodinated sugar was given to
      members of 18 and 60 families in a mildly (urinary iodine < 5.1 micrograms/dl)
      and moderately (urinary iodine < 3 micrograms/dl) iodine deficient areas,
      respectively, over a 1-month and a 6-month period, respectively. In both tests,
      improvements were recorded, i.e. the rates of goitre decreased, urinary iodine
      levels increased significantly (from 5.1 to 14.4 micrograms/dl and from 3 to 9.8
      micrograms/dl, respectively) and thyroid hormones values rose. No side effects
      were noted. The results indicate that fortification of sugar with iodine may
      serve as a new alternative approach in attempts to eradicate iodine deficiency
      related disorders in endemic areas.

PMID- 7584176
TI  - Intra-articular osteoid osteoma of the humerus with synovitis simulating chronic
      monoarthritis of the elbow in a recreational tennis player.
AB  - We present a case of intra-articular osteoid osteoma of the humerus simulating
      chronic monoarthritis of the elbow in an 18-year-old male right-handed
      recreational tennis player. CT revealed a well-defined nidus in the coronoid
      fossa. Microscopic examination of the synovium showed a lymphofollicular
      synovitis that resembled the synovitis in rheumatoid arthritis.

PMID- 7584169
TI  - Dietary intake of fruits and vegetables in Norway: influence of life phase and
      socio-economic factors.
AB  - The aim of the study was to contribute to a better understanding of factors
      influencing the consumption of fruits, vegetables and potatoes among consumers in
      Norway. It is built on data from two consumer surveys; one including 1103 persons
      and the other including 13,857 persons. The data indicate that a considerable
      proportion of the consumers had a very low frequency of consumption when compared
      to present recommendations of intake; 31% consumed vegetables, and 24% fruits
      twice a week or less. Data from multivariate analyses (logistic regression)
      showed that age, sex, income and household structure were important determinants
      for the consumption of fruits. These factors, as well as education and place of
      living were important determinants of the consumption of vegetables and potatoes.
      Consumers who were very interested in health issues, were more likely to have a
      high consumption of fruits and vegetables, whereas those who had a preference for
      quickly prepared food tended to have a low consumption of vegetables. These
      results are discussed in relation to the consumers own perception of important
      limitations for consumption of these products.

PMID- 7584174
TI  - Retropatellar forces after rupture of the PCL and patello-tibial transfixation:
      an in vitro study.
AB  - Compared to injuries of the other knee ligaments, a rupture of the posterior
      cruciate ligament (PCL) is relatively rare. Treatment may be conservative or
      operative. A rupture that has been operated on temporarily can be stabilised
      using a Grammont patello-tibial transfixation (olecranisation). Flexion and
      extension between 30 degrees and 60 degrees are allowed. The advantage of this
      method is that it avoids complete immobilisation of the joint and also the
      reduction of pull on the PCL. However, patients treated with this method show
      long-term osteoarthritis of the retropatellar joint area. Our study aimed to show
      the distribution of forces at the dorsal patellar surface in the following: (1)
      knee with intact ligaments; (2) knee with PCL rupture; (3) knee with PCL rupture
      plus olecranisation. Fourteen fresh knee specimens were investigated in a
      Plitz/Wirth knee kinemator. The femur was fixed while the tibia was flexed
      between 5 degrees and 120 degrees. Pull was placed on the patella and on the
      dorsal side of the tibia with weights over the tendons of the quadriceps and the
      roots of the ischio-crural muscles. With the aid of a special measurement device
      in the patella, the medially laterally, proximally and distally acting forces in
      a movement cycle could be measured as well as the total retropatellar force in
      the above experimental setups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584173
TI  - Kinematic and dynamic axial computerized tomography of the normal patellofemoral
      joint.
AB  - Fourteen normal volunteers with no history suggesting previous or current knee
      pathology underwent axial computed tomographic examination of the patellofemoral
      joint. There were 11 men and 3 women, whose ages ranged from 10 to 46 years
      (average 25 years). Axial images were obtained at 0 degrees, 10 degrees, 20
      degrees, 30 degrees, 40 degrees, and 60 degrees flexion both with and without
      contraction of the thigh muscles. Thus, 12 images were obtained for each
      individual. The CT scanner was focused at the midpatellar level prior to each
      image. Three measurements were made on 24 knees for each individual: congruence
      angle (CA), patellar tilt angle (PTA), and sulcus angle (SA). PTA increased
      slightly from 0 degrees to 20 degrees, and decreased slightly with more flexion
      (not significant, NS). The lower limit of PTA was usually 9 degrees-10 degrees;
      it was not lower than 7 degrees in any knee position. Muscle contraction
      increased PTA slightly at each degree of flexion (NS). Mean CA was +18.3 degrees
      (SD 20.8 degrees) at 0 degrees, which means that normal individuals may have CAs
      as high as +39 degrees at full extension. There was a gradual decrease in CAs
      with knee flexion. The mean values became negative between 20 degrees and 60
      degrees flexion. Contraction of the thigh muscles caused lateralisation of the
      patella except at 30 degrees and 40 degrees flexion. This lateral pull was
      statistically significant at full extension (P < 0.01) and at 10 degrees flexion
      (P < 0.05). The SA decreased gradually as the flexion of the knee
      increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584172
TI  - 1994 Nicola Cerulli Young Researchers Award. Downhill walking: a stressful task
      for the anterior cruciate ligament? A biomechanical study with clinical
      implications.
AB  - Accelerated rehabilitation after anterior cruciate ligament (ACL) reconstruction
      has become increasingly popular. Methods employed include immediate extension of
      the knee and immediate full weight bearing despite the risks presented by a graft
      pull-out fixation strength of 200-500 N. The purpose of this study was to
      calculate the tibiofemoral shear forces and the dynamic stabilising factors at
      the knee joint for the reasonably demanding task of downhill walking, in order to
      determine whether or not this task presented a postoperative risk to the patient.
      Kinematic and kinetic data were collected on six male and six female healthy
      subjects during downhill walking on a ramp with a 19% gradient. Planar net joint
      moments and mechanical power at the knee joint were calculated for the sagittal
      view using a force platform and videographic records together with standard
      inverse dynamics procedures. A two-dimensional knee joint model was then utilised
      to calculate the tibiofemoral shear and compressive forces, based on the
      predictions of joint reaction force and net moment at the knee. Linear envelopes
      of the electromyographic (EMG) activity recorded from the rectus femoris,
      gastrocnemius and biceps femoris muscles were also obtained. The maximum
      tibiofemoral shear force occurred at 20% of stance phase and was, on average, 1.2
      times body weight (BW) for male subjects and 1.7 times BW for female subjects.
      The tibiofemoral compressive force was 7 times BW for males and 8.5 times BW for
      females during downhill walking. The hamstring muscle showed almost continuous
      activity throughout the whole of the stance phase.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7584171
TI  - Factors of patellar instability: an anatomic radiographic study.
AB  - We analyzed the radiographs and computed tomography (CT) scans of 143 knees
      operated on for symptomatic patellar instability and 67 contralateral
      asymptomatic knees, together with 190 control knee radiographs and 27 control
      knee scans, to determine the factors affecting patellar instability. Four factors
      were relevant in knees with symptomatic patellar instability: (1) Trochlear
      dysplasia (85%), as defined by the crossing sign (96%) and quantitatively
      expressed by the trochlear bump, pathological above 3 mm or more (66%), and the
      trochlear depth, pathologic at 4 mm or less. (2) Quadriceps dysplasia (83%),
      defined a present when the patellar tilt in extension is more than 20% on the CT
      scans. (3) Patella alta (Caton-Deschamps) index greater than or equal to 1.2
      (24%). (4) Tibial tuberosity-trochlear groove, pathological when greater than or
      equal to 20 mm (56%). The factors appeared in only 3%-6.5% of the control knees.
      The etiology of patellar instability is multifactorial. Determination of the
      factors permits an effective elective therapeutic plan which aims at correcting
      the anomalies present.

PMID- 7584175
TI  - Synovial fluid cytokine concentrations as possible prognostic indicators in the
      ACL-deficient knee.
AB  - Approximately 44% of patients develop osteoarthritis (OA) following rupture of
      the anterior cruciate ligament (ACL) if the injury is left unrepaired. Restoring
      knee stability through reconstruction, while providing symptomatic relief, has
      not been shown to reduce the incidence of degenerative changes. In fact, recent
      studies have shown that 50%-60% of ACL-reconstructed patients go on to develop
      degenerative changes or frank osteoarthritis. In light of these data, our group
      suggests that the cause of post-traumatic osteoarthritis is not biomechanical but
      biochemical. To test this hypothesis, we measured levels of nine cytokines which
      are important in modulating physiological and pathophysiological metabolism of
      cartilage in knee joint synovial fluid following ACL rupture. Our patient
      population contained both acute and chronic ACL ruptures. A total of 84 samples
      were collected and analyzed by enzyme-linked immunosorbent assay. On the basis of
      the data collected, we were able to identify subgroups of patients who, on the
      basis of their synovial fluid cytokine profile, may be at greater or lesser risk
      of developing post-traumatic OA. In general, patients displayed concentrations of
      interleukin-1 alpha (IL-1 alpha), basic fibroblastic growth factor (bFGF),
      transforming growth factor-beta (TGF-beta), granulocyte/macrophage-colony
      stimulating factor (GM-CSF), IL-6, and IL-8 that we interpreted as being
      consistent with an inflammatory reaction. Of great interest is the fact that the
      levels of these cytokines were very similar in patients 4 weeks after injury and
      in chronic patients, leading us to hypothesize that a chronic smoldering
      inflammatory reaction persists after resolution of the acute effusion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584178
TI  - Kinematics of successful knee prostheses during weight-bearing: three-dimensional
      movements and positions of screw axes in the Tricon-M and Miller-Galante designs.
AB  - Using roentgen stereophotogrammetric analysis we recorded the three-dimensional
      movements in six knees with implanted Tricon-M prostheses and ten knees with
      Miller-Galante prostheses as the patients ascended a platform. Fourteen patients
      with normal knees were used as controls. The two prosthetic designs displayed
      decreased internal tibial rotation and the Tricon-M increased valgus rotation. A
      central point on the tibial articular surface had a more lateral position in the
      Tricon-M design and a more distal one in the Miller-Galante design compared to
      normal knees. Increased posterior displacement with increasing flexion was
      observed in both designs. When the normal knees were extended at full weight
      bearing the helical axes mainly shifted inclination in the frontal plane. In the
      prosthetic knees there was a tendency to anterior-posterior displacement of the
      axes as extension proceeded, especially in the Miller-Galante design.
      Translations along the helical axes were larger than normal in the Miller-Galante
      and smaller in the Tricon-M knees, reflecting differences in constraint of the
      two designs.

PMID- 7584179
TI  - Non-union of a midshaft anterior tibial stress fracture: a frequent complication.
AB  - We report a case of non-union of a midshaft anterior cortex tibial stress
      fracture and review the literature concerning this pathological entity. This is a
      relatively rare clinical form of tibial stress fracture which often results in
      delayed union, non-union or complete fracture. Initial management is as for a
      conventional stress fracture, associated in some cases, according to certain
      authors, with pulsing electromagnetic field physiotherapy. If after 4-6 months no
      sign of union is present, surgical management is indicated, in the form of
      excision of the fracture site with or without bone graft.

PMID- 7584170
TI  - Neural and vascular complications of arthroscopic meniscal surgery.
AB  - Injuries to vessels and nerves are very rare complications of arthroscopic
      meniscal surgery. The clinical development and diagnosis of such complications
      are described and illustrated by cases described in the literature and by two of
      our own cases. Typical patterns of injury are simulated by dissection of cadaver
      knees. To avoid neural complications in suturing the menisci, on the medial side
      the joint capsule has to be prepared when using the inside-out or the outside-in
      technique. On the lateral side of the outside-in technique can be performed by
      small suture incisions in this area when the lateral knee structures can be
      palpated. When using the inside-out technique the peroneal nerve must be
      dissected free. When resecting the posterior horn of the medial meniscus forced
      external rotation of the knee should be avoided because in this position the
      popliteal artery and the medial inferior genicular artery lie close to the
      posterior horn.

PMID- 7584177
TI  - Measurement of stress-strain relationship and stress relaxation in various
      synthetic ligaments.
AB  - In an experimental study various synthetic augmentation devices for knee ligament
      surgery were tested in a servo-mechanical universal tensile testing machine under
      uniaxial loading. Two tests were done to elucidate the mechanical behaviour:
      stress relaxation and stress-strain relationship. Regarding the point of failure
      or rupture, the strongest ligament was the Trevira at 1800 N, followed by the 8
      mm-wide Kennedy LAD at 1720 N. At a working load of 500 N the Gore-tex band, the
      Trevira, and the Kennedy-LAD stretched by between 2% and 3%. For synthetic
      augmentation in repair of proximally ruptured anterior cruciate ligaments we
      recommend a synthetic ligament that reaches failure point at a load of more than
      1000 N with an alteration in length of less than 5%. Otherwise, stress protection
      of the biological reconstruction in full extension will be impossible. The
      requisite criteria were fulfilled by the Trevira, Kennedy-LAD and Gore-tex
      synthetic ligaments.

PMID- 7584181
TI  - Posterior cruciate ligament (PCL) reconstruction--an in vitro study of isometry.
      Part I. Tests using a string linkage model.
AB  - In six intact cadaver knees, we measured how the distance between six selected
      points in and around the femoral and tibial attachment area of the posterior
      cruciate ligament (PCL) changed with knee flexion. After complete removal of the
      PCL, 2-mm drill holes were made at the selected points. Each femoral point was
      measured against each tibial point using a heavy string that was passed through
      the drill holes. The distal end of the string was attached to a measuring unit.
      The changes in femorotibial distance were noted during flexion from 0 degrees to
      110 degrees in 10 degree steps. The tibial drill hole locations had only a minor
      effect on the changes in femorotibial distance. The most isometric point was
      located in the centre of the posterior intercondylar area. The femoral locations
      of the drill holes were the primary determinant of whether the distance
      increased, decreased or remained nearly constant. According to our results, the
      most isometric femoral point is located at the posterosuperior margin of the
      anatomical PCL attachment. Using the tibial isometric point as a reference, the
      femoral points positioned anterior or posterior to the isometric point produced
      considerable changes in the femorotibial distance upon knee flexion. The anterior
      point led to an increase of about 7-8 mm at 110 degrees of flexion, the posterior
      point to a decrease of the same extent. Much smaller changes in femorotibial
      distance resulted from the points located superior or inferior to the femoral
      isometric point.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584183
TI  - Comparative evaluation of different anchoring techniques for synthetic cruciate
      ligaments. A biomechanical and animal investigation.
AB  - Under certain well-defined indications alloplastic material may be used in
      cruciate ligament surgery. The stability and survival of such a synthetic
      ligament is to a great extent dependent on the anchorage with which it is
      fastened to the bone. Most fixation methods have proved to be too weak or have
      revealed other essential drawbacks, resulting in clinical and experimental
      failure. A new ligament fixation device (LFD) was developed and tested
      biomechanically and in animal experiments. In the biomechanic investigation the
      new LFD was compared to single staples, double staples in the belt-buckle
      technique, and ligament guidance through additional bone tunnels (Z-technique).
      The tests were carried out on human cadaver knees, plastic bones, and dog stifle
      joints. The evaluated parameters were linear and maximum load, stiffness, and
      elongation. In addition, hysteresis tests were performed to assay the long-term
      resistance of the fixation. The tests showed a significant superiority of the LFD
      in all measured variables compared to the other anchorages. The pull-out
      strength, at 1866 +/- 43 N (cadaver knee), was about four times that for the
      single staple, and about twice as high as that for the double staple and Z
      technique. The animal experiments were performed on German shepherd cross-breed
      dogs. In six animals the anterior cruciate ligaments were excised bilaterally and
      replaced by a 6-mm Trevira ligament, on one side anchored with staples in the Z
      technique, on the other with the LFD. Postoperatively the dogs were allowed to
      move freely; no additional protection was employed. After 6 months the animals
      were sacrificed and the knees examined macroscopically, radiologically,
      microscopically, and by biomechanical testing. After half a year of implantation,
      the pull-out strength of the alloplastic ligament was 662 +/- 62 N for the LFD
      and 531 +/- 67 N for the staples. Three ligaments in the staple group and one in
      the LFD group had ruptured completely, and two ligaments partially, one in each
      group. The average anterior drawer in the LFD group was 2.8 mm, in the staple
      group 4.0 mm. In all cases the alloplastic ligament was separated from the bone
      by a fibrous interface. None of the fixation devices showed signs of loosening.
      There was no foreign body reaction around the anchorages. Major cartilage
      degeneration was observed in two stifle joints of each group, mainly associated
      with instability.

PMID- 7584182
TI  - Posterior cruciate ligament (PCL) reconstruction--an in vitro study of isometry.
      Part II. Tests using an experimental PCL graft model.
AB  - Isometric positioning of the posterior cruciate ligament (PCL) graft is important
      for successful reconstruction of the PCL-deficient knee. This study documents the
      relationship between graft placement and changes in intra-articular graft length
      during a passive range of motion of the knee. In eight cadaveric knees the PCL
      was identified and cut. The specimens were mounted in a stabilising rig. PCL
      reconstruction was performed using a 9-mm-thick synthetic cord passed through
      tunnels 10 mm in diameter. Three different femoral graft placement sites were
      evaluated: (1) in four specimens the tunnel was located around the femoral
      isometric point, (2) in two specimens the tunnel was positioned over the guide
      wire 5 mm anterior to the femoral isometric point, (3) in two specimens the
      tunnel was positioned over the guide wire 5 mm posterior to the isometric femoral
      point. In all knees only one tibial tunnel was created around the isometric
      tibial point. The location of the isometric points is described in part I of this
      study. The proximal end of the cord was fixed to the lateral aspect of the femur.
      Distally, the cord was attached to a measuring unit. The knees were flexed from 0
      degrees to 110 degrees, and the changes in the graft distance between the femoral
      attachment sites were measured in 10 degrees steps. Over the entire range of
      motion measured, the femoral tunnels positioned around the isometric point
      produced femorotibial distance changes of within 2 mm. The anteriorly and
      posteriorly placed tunnels produced considerable changes in femorotibial distance
      with knee flexion, e.g. about 8 mm at 110 degrees of flexion.

PMID- 7584180
TI  - Strain-related long-term changes in the menisci in asymptomatic athletes.
AB  - In 82 asymptomatic subjects aged 8-62 years we evaluated the menisci by magnetic
      resonance imaging [MRI; 1.0 tesla; spin-echo (SE 700/20), PS (partial saturation;
      500/10), STIR (short time inversion recovery sequence; 1600/130/30)]. For grading
      the degeneration of the meniscus we used a standard classification (grades 0-4).
      MR findings were correlated with the patients' age, weight, profession, and
      athletic activity. Statistic analysis revealed a correlation between athletic
      activity and meniscal degeneration of both anterior horns and the posterior horn
      of the lateral meniscus. Especially the anterior horn of the lateral meniscus
      seems to be loaded during athletic activities. Correlation of meniscus
      degeneration with subjects' age showed an increase in grade 3 and grade 4 lesions
      with advancing age. Among subjects older than 50 years, grade 3 and 4 lesions
      were present in the SE sequence in 28.5% of cases, in PS sequences in 40.7% of
      case, and in STIR sequences in 25% of cases. CLINICAL RELEVANCE: Athletic
      activity seems to load the anterior knee compartments, especially the lateral
      compartment. MRI shows meniscal lesions in a significant number of asymptomatic
      subjects, especially those older than 50 years.

PMID- 7584186
TI  - McMurray's test tested.
AB  - We studied the validity of McMurray's test for a torn meniscus in 93 patients.
      The clinical test results were compared with arthroscopic and/or arthrotomy
      findings as reference. The clinical test had a sensitivity of 58.5%, a
      specificity of 93.4%, and the predictive value of a positive result was 82.6%.
      The test therefore seems to be of limited value in current clinical practice.

PMID- 7584184
TI  - Nerve supply of anterior cruciate ligaments and of cryopreserved anterior
      cruciate ligament allografts: a new method for the differentiation of the nervous
      tissues.
AB  - We investigated the nerve supply of anterior cruciate ligaments ((ACLs) and of
      cryopreserved bone-ACL-bone allografts in a rabbit model with immunohistochemical
      methods to establish the distribution pattern of the nervous tissues and to
      determine the reinnervation rate of ACL allografts. The ACL is innervated by
      three different classes of nerve fibre: (1) fibres of large diameter,
      characterized by neurofilament immunoreactivity, which are fast-conducting
      mechanoreceptive sensory afferents; (2) fibres of small diameter, characterized
      by substance P-immunoreactivity, which are slow-conducting nociceptive sensory
      afferents; and (3) sympathetic efferent vasomotor fibres, characterized by their
      immunoreactivity to the rate-limiting enzyme of noradrenaline synthesis, tyrosine
      hydroxylase. The ACLs showed numerous fibres of all three nerve classes; as
      specialised sensory nerve endings only Ruffini corpuscles were observed. All
      nerve fibres were located subsynovially, none within the collagen core of the
      ligament itself. No nerve fibres were detected in the ACL allografts at 3 and 6
      weeks. Sparse fibres were detected at 12 weeks, while the 24-, 36- and 52-week
      specimens showed plenty of all three fibre types. No mechanoreceptors were found
      in the ACL allografts. To our knowledge, this method for the first time allows a
      differentiation of the nerve fibres of ACLs and ACL allografts into three
      different nerve fibre classes with known neurophysiological functions.

PMID- 7584185
TI  - Theo van Rens Prize. Arthroscopic assessment of the unstable shoulder.
AB  - The purpose of this study was to evaluate prospectively the findings during
      shoulder arthroscopy in patients with recurrent anterior instability of the
      glenohumeral joint. One hundred and seventy-eight patients who fulfilled the
      criteria of having had at least one documented shoulder dislocation were included
      in the study. The pathological findings most frequently noted at arthroscopy
      were: anterior glenoid labral tears (85%), ventral capsule insufficiency (80%),
      Hill-Sachs compression fractures (67%), glenohumeral ligament insufficiency
      (55%), rotator cuff tears (20%), posterior glenoid labral tears (8%), and SLAP
      lesions (5%). Abnormalities were noted more frequently than expected, and there
      were significant differences between preoperative and postoperative diagnoses.
      Our study has taught us that a multiplicity of morphological changes are
      associated with instability of the glenohumeral joint, and that there is no
      single cause. The labrum and rim of the anterior inferior glenoid, for instance,
      showed typical abnormalities corresponding to different entities of anterior
      instability. In practice, this is very important, as the abnormalities visualized
      by imaging methods determine the surgical treatment.

PMID- 7584187
TI  - Arthroscopic treatment of the flexed arthritic knee in active middle-aged
      patients.
AB  - Twenty patients (22 knees) treated by arthroscopic removal of the anterior tibial
      osteophyte were selected for review from more than 150 arthroscopic debridements
      of the knee over a 5-year period (1986-1991). All the patients were middle-aged
      active individuals with competitive sports activity in their past. Their main
      complaint was flexion deformity of the knee (5 degrees-20 degrees) associated
      with pain and discomfort in recreational sporting activities and/or in activities
      of daily living. Roentgenographic examination in all cases showed an anterior
      tibial osteophyte located just anterior and medial to the anteromedial tibial
      spine of the intercondylar eminence. No varus or valgus malalignment or
      subchondral necrosis was detected. Arthroscopic treatment consisting of removal
      of the anterior tibial osteophyte by shaving and extraction of the bone, followed
      by a moderate notchplasty, was sufficient to improve the active extension of the
      knee and to decrease the pain and stiffness of the joint.

PMID- 7584188
TI  - Problems in regaining full extension of the knee after anterior cruciate ligament
      reconstruction: does arthrofibrosis exist?
AB  - A total of 194 patients was reviewed after ACL reconstruction using a patellar
      tendon graft or Leeds-Keio prosthesis supplemented with a MacIntosh lateral
      substitution. There were five groups of patients: patellar tendon with cast
      immobilisation in flexion (n = 34); restricted extension but no cast (n = 40);
      immediate full extension (n = 40); 40); immediate full extension with notch
      widening (n = 40); Leeds-Keio ligament prosthesis (n = 40). The incidence of a
      click or a block to extension requiring operation ranged from 59% following cast
      immobilisation to 2.5% with the Leeds-Keio ligament. The incidence was
      significantly less when a Leeds-Keio prosthesis was used, and these problems may
      be associated with biological materials only. Restricting extension after
      operation significantly increased the loss of extension, confirming the work of
      others. Loss of extension was due to a mechanical block in all cases examined
      arthroscopically. All were relieved by arthroscopic surgery, and no case of
      flexion contracture or arthrofibrosis was encountered. A simple mechanical block
      to extension caused by a Cyclops lesion should be clearly distinguished from
      flexion contracture and arthrofibrosis, conditions which are probably extremely
      rare and overdiagnosed.

PMID- 7584190
TI  - Arthroscopy of the knee without pathological findings.
AB  - From 1983 to 1990, 82 knee arthroscopies (8.2%) carried out in our patients found
      nothing pathological. Sixty-four percent of these patients were active in sports,
      but trauma was noted in 32% of the cases only. Football and other ball games,
      skiing, and track and field athletics were the main causes. Twenty-six percent of
      the patients had undergone previous surgery in the affected knee. At a mean of
      4.6 years postoperatively, clinical and radiological re-assessment was conducted
      so as to compare our pre- and intraoperative findings with the further course of
      events. We found that 48.2% of the patients were symptom-free after the
      diagnostic arthroscopy, 37.5% had persistent discomfort and 14.3% had a
      recurrence of discomfort after 6 months to 2 years. The objective measurement
      score (Zarins Rowe score), at 47.5 out of 50 points, was better than the
      subjective score, at 40 out of 50 points. Our diagnoses had to be changed
      retrospectively: meniscal lesions were diagnosed too frequently, while
      chondropathia patellae and instability were often missed. Additionally,
      complaints could be related to abnormal axis, limited range of motion of the hip
      or knee, leg length inequality and hypermobility. Being unable to verify a
      presumed intra-articular lesion arthroscopically is frustrating for both doctor
      and patient. Our data suggest that meniscal signs should be looked at more
      critically and emphasise the need for a complete evaluation of the whole
      locomotor system.

PMID- 7584189
TI  - Which factors influence the progression of degenerative osteoarthritis after ACL
      surgery?
AB  - The knee radiographs of 77 patients were examined by two physicians not involved
      in the operation a mean of 41.2 months after implantation of a synthetic ligament
      (Trevira hochfest). They evaluated the increase of degenerative osteoarthritis on
      a five-grade scale (0-4) by Jonasch and Mohing as modified by Holz, and using the
      IKDC score. Fifty patients with acute rupture had the synthetic ligament
      implanted for protection of anterior cruciate repair. Twenty-seven patients had a
      salvage procedure with the alloplastic ligament functioning as a prosthesis. Both
      examiners found a statistically significant increase of degenerative arthritis.
      Patients with acute anterior cruciate tears had a lower degree of osteoarthritis
      on the day of surgery compared to the patients with chronic insufficiency, but
      the postoperative increase was identical in both groups. Statistical analysis
      revealed correlations between osteoarthric changes and several factors such as
      concomitant meniscus or posterior cruciate injury and demonstrated no correlation
      to the grade of postoperative stability or injuries to the medial or lateral
      collateral ligaments or capsule.

PMID- 7584191
TI  - Significance of laser treatment in arthroscopic therapy of degenerative
      gonarthritis. A prospective, randomised clinical study and experimental research.
AB  - To ascertain the efficiency of different techniques of arthroscopic therapy for
      gonarthritis and establish the relevance of the extent of chondromalacia,
      clinical and experimental studies were performed. In principle, the process of
      chondromalacia determines the course of the disease. Treatment of additional
      meniscus lesions temporarily leads to better clinical results, but after only a
      few months the symptoms caused by the arthritic process reappear. Compared with
      the temporary relief of complaints after debridement and lavage, smoothing with a
      xenon chloride excimer laser in grade II chondromalacia leads to statistically
      significantly better clinical results. Scanning electron microscopic studies
      confirm the extremely good smoothing. These studies permit clear statements as to
      the various methods of treatment and their application in the different grades of
      chondromalacia, thus leading to differentiated arthroscopic treatment of
      degenerative gonarthritis.

PMID- 7584193
TI  - Proceedings of the ESSKA Scientific Workshop on Reconstruction of the Anterior
      and Posterior Cruciate Ligaments.

PMID- 7584192
TI  - A comparative study of single- and double-bundle ACL reconstructions in sheep.
AB  - Work in vitro has previously shown superior restoration of knee stability using a
      double-bundle anterior cruciate ligament (ACL) reconstruction compared with
      single bundles taken through the condyle or 'over the top'. This paper describes
      an animal study designed to compare the three ACL reconstructions in vivo, in
      order to collect data that could support the clinical use of a double-bundle
      reconstruction. The three methods were compared in three groups of eight sheep,
      the ovine ACL having a distinct double-bundle structure. Biomechanically matched
      polyester fibre implants were used, with 6 months in vivo. The three methods led
      to similar intra-articular fibrous tissue integration of the implants and no
      evidence of implant damage, and biomechanical testing found greater laxity than
      normal for all three groups. The double-bundle group, however, had more joint
      surface degeneration than the other groups. It was concluded that clinical use of
      the double-bundle reconstruction was not indicated by the results of this
      experiment, in view of the more complex surgery and lack of superior performance.

PMID- 7584194
TI  - Positioning of the posterior cruciate ligament.
AB  - The isometric position in ligament reconstruction is the one in which there is
      little or no change in the length of the graft with range of motion of the joint.
      It varies according to the positions of the tunnels that will become the
      attachment sites of whatever graft is being used. Better understanding of this
      concept that greatly improved the surgical results of intra-articular
      reconstructions of the anterior cruciate ligament. Unfortunately, the results of
      posterior cruciate ligament (PCL) reconstructions have lagged behind. A better
      understanding of the isometry of the PCL and how it relates to the positioning of
      a graft at the time of reconstruction should help improve the situation. The
      current scientific studies on the PCL as they relate to isometry are evaluated
      and summarised in this paper. The tibial isometric point was universally less
      sensitive to changes in position than was the femoral isometric point. However,
      all the points that were evaluated for the tibia fell within the normal insertion
      area of the PCL. This has important ramifications when extrapolating these
      laboratory studies to the operating room, where it is imperative to get the
      tibial tunnel or attachment site distal enough on the tibia so that it will be in
      the usual anatomic location of the PCL. There is less uniformity when it comes to
      the femoral isometric point, but once again the isometric point from each of the
      studies fell within the normal anatomic femoral attachment site. The differences
      between the selected points may be explained by the different study designs.

PMID- 7584196
TI  - Occult posttraumatic bone injury.
AB  - Knee injury evaluation with magnetic resonance imaging (MRI) has enabled a high
      percentage of associated diagnoses of occult bone injuries. An experimental
      occult bone injury was produced in the rabbit knee with a controlled impact in
      the range of approximately half the fracture force. An MR image of the occult
      bone injury was obtained after killing the animals at 1, 3 and 9 weeks after
      impact. Histological study of the area under optical microscopy showed a benign,
      self-resolving injury pattern in the subchondral cancellous bone. The samples
      were compared with 11 human biopsy samples obtained during knee surgery. The same
      benign pattern was observed except for one case. The healing response of this
      injury at the subfracture level appears rather benign, and a permanent scar will
      probably not develop.

PMID- 7584195
TI  - Tibial attachment area of the anterior cruciate ligament in the extended knee
      position. Anatomy and cryosections in vitro complemented by magnetic resonance
      arthrography in vivo.
AB  - Knowledge of the anatomy of the anterior cruciate ligament (ACL), including its
      course and orientation in relation to the roof of the intercondylar fossa, is a
      prerequisite for successful intra-articular ACL reconstruction. To attain
      precision placement of the tibial attachment site and to avoid graft/roof
      conflict in the extended knee position, we assessed the anteroposterior tibial
      insertion of the ACL in the midsagittal plane of the extended knee. We measured
      the anterior-posterior (AP) limits and the center of the tibial attachment area
      of the ACL from the anterior tibial margin. The inclination angle of the
      intercondylar fossa roof was measured with respect to the shaft axis of the
      femur. The tibial attachment area of the ACL was determined in ten cadaveric
      knees. Using the cryoplaning technique, we determined the tibial attachment of
      the ACL in five knees. Using contrast magnetic resonance arthrography (MRA), we
      measured the tibial insertion of the ACL in 35 patients (23 male and 12 female)
      with intact ACLs. The total AP midsagittal diameter of the tibia averaged 51.0 +/
      5.8 mm in the cadaveric knees, 49 mm on cryosections, and 53.7 mm in men and
      49.0 mm in women with MRA. The average anterior limit of the ACL, measured from
      the anterior tibial margin, was 14 +/- 4.2 mm in the cadaveric knees, 12.1 mm at
      cryosectional anatomy, and 15.2 mm in men and 13.4 mm in women with MRA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584197
TI  - Anterior cruciate ligament reconstruction using cryopreserved irradiated bone-ACL
      bone-allograft transplants.
AB  - Bone-ACL-bone allograft transplantation has been investigated as a potential
      solution to reconstruction of the anterior cruciate ligament (ACL). To minimize
      disease transmission (e.g. the acquired immuno deficiency syndrome), bony and
      collagenous tissues should be sterilized. Recent animal studies indicate that
      gamma irradiation and ethylene oxide sterilization result in diminished
      histological and biomechanical properties. The purpose of the present study was
      biomechanical and histological determination of the fate of deep-frozen gamma
      irradiated (2.5 Mrad) canine bone-ACL-bone allografts with argon gas protection.
      Particular attention was paid to collagenous and neuroanatomical morphology 3, 6
      and 12 months after implantation, by comparison to a non-irradiated control
      group. Sixty skeletally mature foxhounds were operated on in this study, divided
      up in two groups of 30 dogs each. In group A animals the ACL was replaced by a
      deep-frozen (-80 degrees C) bone-ACL-bone LAD-augmented allograft subjected to
      2.5 Mrad gamma irradiation with argon gas protection. The animals in group B
      received an LAD-augmented ACL-allograft transplant without gamma irradiation. All
      knees from both groups were evaluated 3, 6 and 12 months after implantation in
      regard to biomechanical properties, collagen morphology and routine histology
      (haematoxylin and eosin stain, polarization microscopy), neuroanatomical
      morphology (silver and gold chloride stain) and microvasculature (modified
      Spalteholz technique). The irradiated ACL allografts withstood a maximum load
      that was 63.8% (718.3 N) of the maximum load of normal ACLs after 12 months. By
      contrast, the non-irradiated allografts failed at 69.1% (780.1 N) of the maximum
      load of normal control ACLs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584199
TI  - Early development of patella infera after knee fractures.
AB  - The condition referred to as patella infera is characterized by a permanent
      shortening of the patellar ligament and is associated with a severely limited
      range of motion of the knee joint. Patella infera is a common complication of
      injury or surgery to the knee joint, and it is generally considered a condition
      that presents after a variable, albeit considerable time after injury. A review
      of the knee roentgenograms of patients with arthrofibrosis and patella infera
      showed this condition to be an immediate complication of knee fractures.
      Therefore, in order to better define the development of patella infera, the
      patellar height was studied during treatment of 146 knee joint fractures (46
      supracondylar fractures, 50 patellar fractures and 50 tibial plateau fractures).
      Using the Caton-Deschamps method patella infera was detected in eight cases
      (17.39%) immediately after supracondylar fractures, in six cases (12%) after
      patellar fractures, and only in two cases (4%) after tibial plateau fractures.
      The patellar ratio remained unchanged or worsened further after treatment, and
      its incidence was unaffected by the type of treatment. These observations rule
      out etiologies such as inflammatory or algodystrophic phenomena and quadriceps
      inhibition, because the reduction of patellar height was evident immediately and
      persisted at follow-up examinations.

PMID- 7584205
TI  - Normal regional anatomy of the shoulder.
AB  - The shoulder joint is a remarkable structure enjoying a greater range of motion
      than any other articulation in the human body. The shoulder is not a single joint
      but actually four separate articulations that act synergistically. The authors
      review the complex anatomy of the shoulder.

PMID- 7584200
TI  - Kinematic and dynamic axial computed tomography of the patello-femoral joint in
      patients with anterior knee pain.
AB  - Thirty-eight knees of 26 patients with anterior knee pain (12 bilateral) were
      included in the study. There were 22 women and 4 men, and their average age was
      29 years. Axial computed tomography (CT) examination of both knees were done at 0
      degrees, 10 degrees, 20 degrees, 30 degrees, 40 degrees and 60 degrees of flexion
      with and without muscle contraction. Images were always taken at the mid-patellar
      level. Patellar tilt angle (PTA), congruence angle (CA) and sulcus angle (SA)
      were measured at each knee position. Normal values were also obtained from 14
      healthy volunteers (28 knees). Thus, the types of patello-femoral incongruence
      were determined at each knee position: 1, tilt + lateralisation (TL: 12 knees);
      2, lateralisation (L: 4 knees); 3, medialisation (M: 5 knees); 4, lateral to
      medial instability (LM: 1 knee); 5, tilt (T: 1 knee). Fifteen knees were
      classified as normal. When the groups were analysed separately, in the TL group
      the T or L component would have been missed in nine cases if the images were
      taken only at 30 degrees or only in the first 30 degrees of flexion. In the L
      group two patellae were reduced at 30 degrees. In three knees in the M group,
      medialisation began at 10 degrees, 20 degrees and 30 degrees. One patella was
      reduced at 40 degrees. In the LM case, the patella was lateralised at 0 degrees,
      10 degrees, 20 degrees and medialised at 30 degrees and 40 degrees. In the T
      case, the patella was tilted only at 20 degrees, 40 degrees and 60
      degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584201
TI  - Opioids as novel intra-articular agents for analgesia following arthroscopic knee
      surgery.

PMID- 7584203
TI  - Chronic Achilles peritendinitis and retrocalcanear bursitis. Long-term follow-up
      of surgically treated cases.
AB  - Forty-nine patients with Achilles peritendinitis (APT) (11 bilateral) and 31
      patients with retrocalcanear bursitis (RCB) (5 bilateral) were treated surgically
      (altogether 96 heels). There were 37 men and 12 women in the APT group, with a
      mean age of 38.4 years, and 26 men and 5 women in the RCB group, with a mean age
      of 32.3 years. Forty-five patients in the APT group and 30 patients in the RCB
      group were active in sports. All patients had been treated conservatively for at
      least 6 months (range 6 months to 13 years) without relief of symptoms. The
      operative method was bilateral longitudinal incision of fascia cruris and
      trimming of the adhesions to fascia and base of Kager's triangle in APT group,
      and ablation of the posterior upper corner of os calcaneus in RCB group. In order
      to assess the ability to return to sports, the healing results were evaluated by
      questionnaire in 42 patients (47 operations) in the APT group and 25 patients (28
      operations) in the RCB group 2-11 years postoperatively. The results were
      excellent in 27, good in 11, fair in 7 and poor in 2 in the APT group, and
      excellent in 13, good in 10, fair in 2 and poor in 3 in the RCB group,
      respectively. Operative treatment of APT and RCB in patients whose symptoms
      persist after conservative treatment seems to give favourable results in the
      majority of cases.

PMID- 7584204
TI  - Synovial hemangioma--a rare benign synovial tumor. Report of four cases.
AB  - We report our clinical experiences in the diagnosis and treatment of four
      patients with synovial hemangiomata. Synovial hemangiomata are rare causes of
      recurrent, nonspecific joint complaints and occur most often at the knee joint.
      Nontraumatic joint swelling combined with recurrent, possibly hemorrhagic joint
      effusions must be considered signs of a synovial hemangioma. Although no
      preoperative diagnostic tool enables confirmation of the diagnosis, and MRI seems
      to be the diagnostic procedure of first choice, it is most important fact for the
      clinician to be aware of the existence of this disease. Early surgical treatment
      with excision of the tumor within wide margins of noninvolved normal synovial
      tissue as partial or total synovectomy is the therapy of choice and avoids
      degenerative changes as demonstrated with the four cases reported here.

PMID- 7584202
TI  - Arthroscopic treatment of anterior synovitis of the ankle in athletes.
AB  - In a retrospective study we analysed the results of arthroscopic treatment of
      anterior synovitis of the ankle in 35 athletes. Five athletes additionally
      suffered from anterior osteophytes, and three presented with an anterolateral
      plica. Their average age was 25 years (SD 8.3), and the follow-up interval was
      32.4 months (SD 19.4). Eight patients suffered from additional hyperlaxity of the
      ankle joint. At the time of follow-up, the patients were examined clinically as
      well as radiologically. The results were scored according to an ankle index
      containing the criteria pain, function, athletic activity, walking aids, range of
      motion and swelling. During surgery a partial synovectomy was performed and
      removal of anterior osteophytes or anterolateral plica as necessary. The overall
      score increased non-significantly from 66.2 preoperatively to 78.7
      postoperatively (P > 0.05). Comparing the different criteria, the score parameter
      pain significantly increased after arthroscopy. All other parameters (function,
      athletic activity, walking aids, range of motion, swelling) showed only slight
      changes in this patient group. Athletes with a hypermobile joint showed worse
      results compared with the others. Even after surgery we documented severe
      restriction concerning athletic activity. Only 9 patients performed their
      activities at their previous level, 19 had reduced their activity level, and 7
      had discontinued their athletic activity. In 6 cases we found temporary
      iatrogenic neurological damage. Regarding the uncertain clinical outcome and the
      documented high risk for neurovascular complication, patient selection for
      arthroscopic partial synovectomy in the athletic population should be extremely
      carefully performed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584208
TI  - Magnetic resonance imaging of the postoperative shoulder.
AB  - The use of MR imaging in the evaluation of the postoperative shoulder and the
      findings indicative of postoperative pathology remain largely unexplored. MR
      imaging does seem to be diagnostic of complete rotator cuff tears following cuff
      repair. In all postoperative cases, a key to differentiating the expected from
      the pathologic is to be familiar with the procedure that was performed.

PMID- 7584207
TI  - Magnetic resonance arthrography of the shoulder.
AB  - Recently, there have been attempts to improve the accuracy of MR imaging by
      distending the glenohumeral joint with fluid prior to imaging. This article
      reviews the techniques employed in performing MR arthrography, imaging
      characteristics of MR arthrography, and diagnostic use of the procedure.

PMID- 7584209
TI  - Magnetic resonance imaging of arthritides affecting the shoulder.
AB  - MR imaging has thus far had a limited role in the evaluation of arthritis
      involving the shoulder. In certain cases, such as in amyloid and synovial osteo
      chondromatosis, however, MR imaging may be virtually diagnostic. It is likely
      that MR imaging will have an expanded role in the evaluation of arthritis in the
      future.

PMID- 7584206
TI  - Glenohumeral instabilities and the role of magnetic resonance imaging techniques.
      The orthopedic surgeon's perspective.
AB  - Orthopedic surgeons often have different philosophies regarding the diagnosis and
      treatment of glenohumeral instability. Some surgeons will rely extensively on
      imaging studies to ascertain pathology relevant to a specific method of
      treatment; others will only use imaging in cases where the diagnosis is
      uncertain. This article reviews the concept of glenohumeral instability and its
      treatment.

PMID- 7584210
TI  - Magnetic resonance imaging of miscellaneous disorders of the shoulder.
AB  - The ability to simultaneously and comprehensively evaluate both articular and
      extra-articular structures represents a distinct advantage for MR imaging over
      all other diagnostic methods. This article reviews how the technique can
      demonstrate a wide spectrum of abnormalities in and around the shoulder, with an
      emphasis on abnormalities encountered during MR imaging that were clinically
      unsuspected at the time of examination.

PMID- 7584211
TI  - Magnetic resonance imaging of the brachial plexus.
AB  - Magnetic resonance imaging is the modality of choice for the evaluation of the
      brachial plexus. Regardless of the cross-sectional imaging modality used, a
      knowledge of the anatomy in the lower neck and thorax is necessary in the
      interpretation of these studies. Before imaging an attempt should be made to
      determine the possible etiology and location of the lesion.

PMID- 7584198
TI  - Combination of cold and compression after knee surgery. A prospective randomized
      study.
AB  - The objective of this study was to investigate the effect of continuous long-term
      application of a combined cooling and compression system (Cryo/Cuff, Aircast
      Inc., Summit, New Jersey, USA) on postoperative swelling, range of motion (ROM),
      pain, consumption of analgesics, and return of function after anterior cruciate
      ligament (ACL) reconstruction. We compared the cold-compression system with
      traditional ice therapy. There were 44 patients in the series (aged 15-40 years)
      who were randomly assigned to a control group (ICE) or a study group (CC). The
      ICE group consisted of 23 patients (aged 24.2 +/- 4.5 years); the CC group
      consisted of 21 patients (aged 24.8 +/- 5.6 years). The ICE group received ice
      bags postoperatively; the CC group was provided with the Cryo/Cuff during the 14
      day hospital stay. Girth, ROM, pain score (visual analog scale), and consumption
      of analgesics were determined on postoperative days 1, 2, 3, 6, 14, and 28.
      Twelve weeks after surgery, isokinetic testing was performed, and the functional
      knee score was determined. In the CC group, significantly less swelling was
      observed (P < 0.035). These patients also reported less pain and had a
      significantly reduced consumption of analgesics (P < 0.04). On all examination
      days, ROM in the CC group was up to 17 degrees greater than in the ICE group (P <
      0.02). The functional knee score was significantly increased in the CC group (P =
      0.025). The results from our study document the advantages of continuous cold
      compression therapy over cold alone following ACL reconstruction.

PMID- 7584212
TI  - Imaging techniques, normal variations, and diagnostic pitfalls in shoulder
      magnetic resonance imaging.
AB  - Various techniques available for performing shoulder MR imaging and methods for
      optimizing technical performance of shoulder MR examinations are reviewed.
      Anatomic variations and diagnostic pitfalls that may be encountered on MR images
      of the shoulder and how these variations may be distinguished from pathology are
      described.

PMID- 7584213
TI  - Pathogenesis of rotator cuff disorders. Magnetic resonance imaging
      characteristics.
AB  - In summary, rotator cuff pathology is a continuum that begins with degeneration
      of collagen fibers at a rate that exceeds that of repair. The degenerative
      process is accelerated with aging, chronic inflammatory diseases, impingement,
      and repetitive activity. A tendon weakened by disease may then be torn by routine
      physical activity. MR imaging can help predict which patients are at risk for
      rotator cuff disease because of abnormal anatomy and can detect the disease at an
      early stage so that the progression may be altered before a tear occurs.

PMID- 7584214
TI  - Magnetic resonance imaging of impingement and rotator cuff tears.
AB  - This article addresses the role of MR imaging in the spectrum of impingement and
      rotator cuff tears. Rotator cuff and coracoacromial arch anatomy, the cause of
      impingement syndrome, and the pathology and imaging of calcific tendinitis are
      reviewed.

PMID- 7584215
TI  - Magnetic resonance imaging of impingement and rotator cuff disorders. A surgical
      perspective.
AB  - In conclusion, the clinical picture of impingement syndrome is one of a continuum
      occurring as a result of compression of the bursa and rotator cuff within the
      subacromial space. In its early stages nonoperative management will often
      suffice, but in resistant cases and in cuff tears operative intervention is often
      indicated. The usefulness of MR imaging has greatly expanded for the orthopaedist
      diagnosing and treating the patient with impingement. After careful clinical
      evaluation and plain radiographs, MR imaging can significantly add to our
      knowledge as to the extent of the disease process. This added information can aid
      in tailoring an individualized treatment regimen and can be invaluable in the
      preoperative planning for patients with rotator cuff pathology.

PMID- 7584217
TI  - Magnetic resonance imaging of glenohumeral instability.
AB  - Familiarity with normal anatomy and pathologic features of the capsulolabral
      complex as well as high resolution imaging are important factors in achieving a
      consistently high accuracy rate in diagnosis of glenohumeral instabilities by
      conventional MR imaging. The various types of glenoid labrum lesions and features
      that are most often associated with glenohumeral instability are defined.

PMID- 7584221
TI  - Venography of the extremities and pelvis.
AB  - The ability of MR imaging to depict flow coupled with the inherent soft tissue
      contrast available on MR images has propelled this modality into the forefront of
      diagnostic imaging. The precise clinical utility of MR angiography is still in
      evolution; therefore, this article focuses on practical approaches to assessing
      the venous system of the extremities and pelvis.

PMID- 7584220
TI  - Magnetic resonance angiography of the peripheral arteries.
AB  - MR angiography techniques have recently been applied to evaluation of peripheral
      vascular disease, both phase-contrast and time-of-flight techniques have been
      used. Preliminary clinical experience has shown promise in identification of
      angioplasty candidates, preoperative evaluation in iliofemoral occlusive disease,
      and identification of tibial run-off vessels.

PMID- 7584219
TI  - Time-of-flight techniques. Pulse sequences and clinical protocols.
AB  - Time-of-flight, the most commonly used angiographic sequence, relies on the
      inflow of bright, relaxed blood into a region whose magnetization is suppressed
      by radiofrequency pulses. Good angiographic contrast relies on pulse rates (i.
      e., repetition times) that are fast enough and pulse amplitudes (i. e., flip
      angles) that are large enough to saturate the magnetization of the background
      without saturating the magnetization of entering blood.

PMID- 7584218
TI  - Magnetic resonance angiography of the body. Physical principles and technical
      challenges.
AB  - Methods for body MR angiography must contend with problems of motion, complex
      flow patterns and geometrics, and suppression of undesired material, while
      striving for adequate spatial resolution and signal-to-noise. Fortunately, MR
      offers a wide array of imaging options to tackle this formidable set of
      challenges, making this field an active area of research and development.

PMID- 7584216
TI  - Magnetic resonance imaging of the biceps complex.
AB  - A variety of disorders primarily involving the long head of the biceps tendon is
      discussed. By virtue of its particular intra-articular position, this tendon may
      be affected by primary articular and degenerative processes because of
      impingement by the coracoacromial arch. Disorders of the biceps, including
      traumatic tears and displacement out of the bicipital groove, are best evaluated
      by MR imaging.

PMID- 7584223
TI  - Portal magnetic resonance angiography.
AB  - MR angiography has shown definite clinical use in the portal venous system.
      Methods have been developed for noninvasive assessment of portal venous anatomy
      and blood flow using a variety of techniques. Time-of-flight techniques for
      portal angiography and both time-of-flight and phase-contrast techniques for flow
      measurement are reviewed.

PMID- 7584222
TI  - Magnetic resonance angiography of the aorta and renal arteries.
AB  - Recently developed MR angiographic techniques currently provide useful
      information regarding arterial vascular abnormalities within the abdomen. With
      further improvements in technique, MR angiography in the abdomen is expected to
      provide the radiologist and clinician with extensive information regarding
      vascular pathology without the need for iodinated contrast or intravascular
      catheters. Further work is needed to evaluate the role of MR angiography with
      respect to other noninvasive imaging techniques.

PMID- 7584224
TI  - Magnetic resonance angiography of systemic thoracic and abdominal veins.
AB  - The development of MR angiography has greatly expanded the use of MR imaging for
      investigating the systemic veins both in the thorax and in the abdomen. With its
      multiplanar imaging capabilities and three-dimensional image acquisition, MR
      angiography is the definitive method for imaging the systemic veins in the vast
      majority of patients.

PMID- 7584225
TI  - Pulmonary arteriography.
AB  - This article reviews current trends in MR angiography of the pulmonary
      vasculature, including both two-dimensional and three-dimensional MR imaging
      techniques. Focus is on those techniques used for the diagnosis of pulmonary
      embolism. Three-dimensional techniques are discussed in more detail,
      demonstrating a combination of two techniques incorporating magnetization
      prepared rapid gradient acquisitions that have added substantial versatility in
      diagnosing pulmonary vascular disease.

PMID- 7584229
TI  - Black-blood and segmented k-space magnetic resonance angiography.
AB  - K-space segmentation can be used to produce both black-blood and bright-blood
      images that improve visualization of blood vessels in the presence of disturbed
      or time-varying flow. When used judiciously, these techniques can serve as
      effective problem-solving tools in clinical situations in which alternative
      techniques are prone to error.

PMID- 7584227
TI  - Phase-contrast magnetic resonance angiography in the abdomen and thorax.
AB  - Clinical applications of phase-contrast MR angiography have been focused mainly
      on the head and neck, and its applications to the thorax and abdomen are still
      limited. This technique, however, has several unique uses that can be used to
      good effect. This articles examines the practical uses of phase-contrast MR
      angiography in the abdomen and thorax.

PMID- 7584228
TI  - Magnetic resonance angiography and flow quantification of coronary arteries.
AB  - Although further work is needed to improve spatial resolution and flow contrast
      as well as to lessen dependence on a regular cardiac rhythm, the potential
      clinical utility of MR coronary angiography is substantial. For the first time,
      information regarding coronary artery anatomy can be acquired in a completely
      noninvasive manner.

PMID- 7584230
TI  - Echo-planar magnetic resonance angiography.
AB  - Practical ultrafast, especially echo-planar, imaging is still in its infancy. All
      the more so for ultrafast angiography. Nevertheless, a few practical forays into
      this imaging application have shown promise. Compared to conventional MR
      angiography, the use of EP imaging can offer net advantages in reduced
      sensitivity both to motion artifacts from gross patient motion and to signal
      losses from changing blood flow velocities. Little work has been done to date on
      obvious application of ultrafast MR angiography (e.g., interleaved phase-contrast
      methods). The few existing reports on this topic suggest that EP imaging may be
      useful for much more exotic applications such as the imaging and velocity
      quantitation of the major coronary arteries. EP imaging will most likely have its
      greatest impact on MR angiography in these more exotic areas, tackling imaging
      problems in the moving structures most difficult to study.

PMID- 7584226
TI  - Magnetic resonance angiography of the thoracic aorta.
AB  - The development of MR angiography techniques has improved the quality of
      information available from MR of the thoracic aorta. With current cine techniques
      and three-dimensional MR angiography, the thoracic aorta can be examined
      noninvasively with a high degree of accuracy.

PMID- 7584231
TI  - Normal magnetic resonance imaging anatomy of the ankle and foot.
AB  - The normal anatomy of the ankle and fore-foot is quite complex and presents a
      challenge for both MR imaging and interpretation. Many of the critical ligaments
      and tendons require imaging in several planes for greatest diagnostic accuracy.
      We hope this article serves as a solid foundation and a reference for the
      excellent articles that follow.

PMID- 7584233
TI  - Magnetic resonance imaging of the diabetic foot.
AB  - MR is useful in evaluating foot abnormalities in diabetic patients. MR offers
      superior spatial resolution over radionuclide bone scans and superior soft tissue
      contrast over CT and radiography. MR is able to localize and distinguish soft
      tissue abscesses from soft tissue edema. MR is sensitive at demonstrating the
      presence and extent of osteomyelitis.

PMID- 7584232
TI  - Magnetic resonance imaging of pediatric disorders of the ankle and foot.
AB  - This article discusses the unique contribution of MR imaging to the evaluation of
      selected pediatric disorders of the ankle and foot. MR imaging is helping to
      unravel the complex congenital malformation of talipes equinovarus. It is the
      study of choice for the examination of intraarticular abnormalities such as
      Trevor's disease. The MR imaging staging of osteochondritis dissecans and
      delineation of a tarsal coalition have shown great promise in guiding surgical
      management of these abnormalities.

PMID- 7584235
TI  - Tumors of the ankle and foot.
AB  - Although tumor and tumor-like conditions of the foot and ankle are unusual,
      certain bone and soft tissue lesions are more common than others. Conventional
      radiographs remain essential in all such cases and are especially specific for
      intraosseous tumors. MR imaging is more sensitive to the presence and extent of
      both bone and soft tissue lesions.

PMID- 7584234
TI  - Magnetic resonance imaging manifestations of synovial lesions of the ankle and
      foot.
AB  - Inflammatory, infectious, neoplastic, degenerative, or idiopathic disorders may
      all be manifested as synovial disease. MR imaging allows noninvasive evaluation
      of synovial disease and is a highly sensitive modality for detection of synovial
      pathology. Intravenous or intra-articular contrast administration will sometimes
      further increase signal differences between inflamed synovium, joint effusion,
      and surrounding structures.

PMID- 7584236
TI  - Technical considerations for magnetic resonance imaging of the ankle and foot.
AB  - The hardware and software factors that impinge on the appearance and quality of
      MR images of the ankle and foot are reviewed. The importance of static field
      strength is discussed. The local (surface) coils that can be applied to this
      anatomic region are reviewed. The properties of the available pulse sequences and
      the differences among them are addressed with particular attention to their
      impact on the imaging of the ankle and foot.

PMID- 7584237
TI  - Clinical significance of magnetic resonance imaging of the ankle and foot.
AB  - Magnetic resonance imaging is of major diagnostic value in foot and ankle
      pathology. It is noninvasive and extremely accurate, and rarely gives false
      negative or false positive results. Any false results are due invariably to poor
      imaging, or inept interpretation by the radiologist or orthopedist or both.
      Diagnostic accuracy is increased by clinical correlation. Magnetic resonance
      imaging is not only a valuable diagnostic tool with respect to the foot and ankle
      but also is often of great value in either indicating or contraindicating surgery
      or modifying the preoperative surgical management. Finally, the orthopedist must
      be aware of the current limitations of MR imaging and not assume that a negative
      reading indicates the absence of pathology.

PMID- 7584240
TI  - Tarsal tunnel syndrome.
AB  - The diagnosis of tarsal tunnel syndrome can be difficult to make. Clinical
      findings may be varied and symptoms are commonly vague and diffuse. MR imaging,
      with its excellent soft tissue contrast and ability to demonstrate
      musculotendinous and neurovascular structures, clearly demonstrates the anatomy
      of the tarsal tunnel and its contents and the presence and extent of lesions
      causing this syndrome.

PMID- 7584238
TI  - Magnetic resonance imaging of ankle ligaments. Emphasis on anatomy and injuries
      to lateral collateral ligaments.
AB  - Ankle ligament sprains are the most frequent sports injury, and radiographic
      evaluation of the ankle accounts for 10% or all radiographic examinations
      requested from an emergency department. This article reviews the diagnosis of the
      ankle sprain and the anatomy and injuries of the ankle ligaments.

PMID- 7584239
TI  - Sinus tarsi syndrome.
AB  - Sinus tarsi syndrome is a clinical-pathologic entity with characteristic MR
      imaging manifestations related to the inflammatory changes and ligamentous tears
      occurring in the hindfoot. Frequently, this entity is associated with other
      tendon and ligamentous injuries of the ankle. Radiologists should be aware of
      this condition to direct their search to the specific MR imaging findings.

PMID- 7584241
TI  - Chronic rupture of the posterior tibial tendon.
AB  - Chronic rupture of the posterior tibial tendon is a common disorder causing a
      progressive flat foot deformity. MR imaging is an excellent modality for
      assessing dysfunction of the tendon. It can easily and accurately detect and
      grade the tears. A variety of secondary soft tissue and bony abnormalities are
      associated with the tear and can be useful in confirming the diagnosis.

PMID- 7584242
TI  - Achilles tendon and miscellaneous tendon lesions.
AB  - Abnormalities of the tendons of the foot and ankle are quite common and their
      number seems to be increasing. Commonly involved tendons include the Achilles and
      peroneal tendons; the tibialis anterior and flexor hallucis longus tendons are
      involved less commonly. Magnetic resonance imaging is well suited to imaging
      these abnormalities. It is a noninvasive modality that uses no ionizing
      radiation. It has the capability of imaging in any plane, which is well suited to
      imaging the tendons of the ankle because their course is not in standard
      orthogonal planes. MR imaging provides excellent soft tissue contrast and is well
      able to differentiate the tendons from surrounding fat as well as to detect the
      presence of hemorrhage and edema. Abnormalities of these tendons include complete
      and partial tears as well as tendinitis and tenosynovitis. These abnormalities
      are usually secondary to trauma or to mechanical irritation or synovial
      inflammation. They can be diagnosed routinely and confidently by MR imaging.
      Complete tears may be seen as a discontinuity within the substance of a tendon
      with interposed edema or hemorrhage. Partial tears may be seen as increased
      signal within a tendon that extends to a surface. Tendinitis is manifested by
      thickening of the tendon with intratendinous signal that does not extend to its
      surface.

PMID- 7584243
TI  - Magnetic resonance imaging of plantar fasciitis and other causes of heel pain.
AB  - Heel pain can be caused by disorders of either the plantar fascia, calcaneus,
      tendons, or adjacent nerves. Because these conditions can lead to pain located in
      a small area of the heel, a precise clinical diagnosis may be difficult. This
      article describes some of these various causes of heel pain and how MR imaging
      helps to characterize them.

PMID- 7584244
TI  - MR angiography of the central nervous system. Basic flow phenomena.
AB  - To properly understand MR angiography and its artifacts, one needs to be firmly
      grounded in the basic physics of MR flow. Concepts such as "flow-related
      enhancement" are crucial to a proper understanding of time-of-flight MR
      angiography. Phase contrast MR angiography draws from the same principles used to
      explain "even echo rephasing." This article not only provides a physical basis
      for MR angiography but also explains the flow phenomena observed on routine MR
      images.

PMID- 7584245
TI  - Time-of-flight method of MR angiography.
AB  - Results of preliminary clinical studies of time-of-flight MR angiography indicate
      that this technique can provide accurate reproducible flow images in different
      anatomic regions of the body. A unique advantage of this technique is its
      capacity to provide multiple projections of complex vascular abnormalities with a
      single data acquisition. This may increase both the sensitivity and specificity
      of MR angiography in some patients with cerebrovascular diseases. Preliminary
      clinical results suggest that time-of-flight MR angiography can screen for
      identification of normal vasculature as well as stenosis and/or occlusions
      produced by atherosclerotic disease.

PMID- 7584246
TI  - Phase contrast MR angiography techniques.
AB  - Phase contrast MR methods encode information from macroscopic motion into the
      phase of the MR signal. Phase contrast methods can be applied with small and
      large fields-of-view, can give quantitative measures of velocity, and provide
      excellent suppression of signals from stationary tissue. Unlike time-of-flight
      methods, phase contrast methods directly measure flow and thus are not hindered
      by the artifactual appearance of tissue having short T1. Phase contrast
      angiograms can be two-dimensional (thin slice or projectile), three-dimensional,
      and/or time resolved and have applications throughout the body.

PMID- 7584247
TI  - Flow quantification and analysis methods.
AB  - The sensitivity of nuclear magnetic resonance to motion can be harnessed to
      produce quantitative measurements of low flow velocity and volume flow rate. MR
      flow quantification is noninvasive, can be performed in arbitrary locations and
      in any image orientation, and is fairly rapid. This article discusses the basic
      techniques with particular attention to phase contrast quantitation of volume
      flow rate, especially the determinants of accuracy and reproducibility in these
      measurements.

PMID- 7584249
TI  - MR angiography of the extracranial carotid arteries.
AB  - As described earlier, if MR angiography is to replace conventional angiography,
      the entire course of the carotid arteries should be imaged. De Marco et al
      describe initial success in imaging the entire circulation from the aortic arch
      through the circle of Willis, combining 2-D and 3-D TOF methods without
      gadolinium, electrocardiograph gating or breath holding. The technique requires 1
      to 1.5 hours of imaging time, and accuracy in establishing tandem lesions is not
      yet established. It is likely that future refinements will allow for more
      widespread acceptance of MR angiography as a sometime alternative to conventional
      angiography.

PMID- 7584248
TI  - Diffusion and perfusion imaging techniques.
AB  - Diffusion imaging techniques including the Stejskal-Tanner and the stimulated
      emission of amplitude echoes (STEAM) pulse sequences are discussed. The
      calculation of apparent diffusion coefficient (ADC) maps is reviewed. The
      perfusion imaging techniques of blood oxygen level dependent (BOLD) and first
      pass bolus perfusion techniques as well as the newer technique of echo-planar
      imaging with signal targeting and altering radiofrequency (EPISTAR) are also
      discussed. Finally, the theory of intravoxel incoherent motion (IVIM) and its
      relationship to both diffusion and perfusion phenomena is examined.

PMID- 7584250
TI  - MR angiography in carotid stenosis. A clinical prospective.
AB  - MR angiography is a major advancement in the diagnosis and treatment of patients
      with carotid artery stenosis. It has become the major preoperative diagnostic
      test for these patients. An understanding of the principles of MR imaging allows
      the clinician to overcome the occasional drawback of MR angiography. Use of MR
      imaging with duplex scanning allows the surgeon to have an extremely accurate
      image of the carotid artery bifurcation. Studies conclude that by using these
      tests as the preoperative assessment for the patient undergoing carotid artery
      endarterectomy, the procedure is performed with decreased complication, as the
      risks of conventional cerebral angiography are avoided.

PMID- 7584251
TI  - Intracranial aneurysms.
AB  - MR angiography provides a rapid, accurate, and extremely flexible noninvasive
      evaluation of intracranial aneurysms without the cost and risk of conventional
      angiography. TOF and phase contrast techniques each have specific advantages and
      disadvantages that can be selectively exploited to optimize aneurysm evaluation.
      Present indications for MR angiography in aneurysm evaluation include: (1) the
      presence of incidental findings on a CT or MR examination that suggest the
      possibility of aneurysm (Figs. 7 and 8), (2) when angiography is contraindicated
      or when the risk is too high, (3) non-invasive follow-up of patients with known
      aneurysms, (4) patient refusal of contrast angiography, and (5) evaluation of
      patients with specific clinical symptoms (i.e., third cranial nerve palsy) or
      patients with non-specific subacute symptoms in whom an aneurysm might explain
      the clinical presentation. Although MR angiography certainly can detect aneurysms
      with a high rate of sensitivity and specificity, detailed decision analyses
      generally have not supported the overall benefit of this type of screening.
      Future technical advances as well as advances in the overall understanding of
      aneurysms may one day prove unequivocally the benefit of MR angiography in
      screening high-risk patient groups. MR angiography has not yet been clinically
      evaluated as a tool in the evaluation of acute subarachnoid hemorrhage. Potential
      obstacles to such an evaluation include the clinical instability of SAH patients,
      limited spatial resolution of the MR angiography acquisitions, the potential for
      subarachnoid blood or focal intraparenchymal hematomas to obscure or mimic small
      aneurysms, and the unreliability of MR angiography in demonstrating vasospasm.
      Currently these factors continue to provide an integral role for contrast
      angiography in aneurysm evaluation.

PMID- 7584252
TI  - Vascular malformations.
AB  - MR angiography supplements conventional MR imaging in the diagnosis and
      evaluation of patients with arteriovenous malformations. MR angiography may also
      have a significant role in the planning and follow up of patients undergoing
      radiosurgical treatment. The technique has a much more limited role in the
      evaluation of vascular formations with low flow or no flow, such as developmental
      venous anomalies, cavernous malformations, and capillary telangiectasis.

PMID- 7584253
TI  - MR imaging and MR angiography in the diagnosis of dural arteriovenous fistulas.
AB  - Intracranial DAVFs are most commonly found in the cavernous, transverse, and
      sigmoid sinuses. MR imaging and MR angiography can be used to screen for these
      lesions and determine if there is cortical venous drainage. Conventional
      angiography still has a major role in screening and is mandatory prior to any
      therapy. Spinal DAVFs are uncommon lesions seen predominantly in older men. The
      diagnosis can be suspected with MR imaging if a large draining vein is seen in
      association with swelling and enhancement of the conus and increased signal on T2
      weighted images. MR angiography shows some promise in identifying the vascular
      anatomy of these lesions.

PMID- 7584254
TI  - Venous disease and tumors.
AB  - MR imaging of the venous system of the brain plays an important role in the
      diagnosis and follow up of intracranial venous vascular diseases. This article
      serves to acquaint the reader with the currently available methods to study the
      venous vascular system in addition to covering specific instances in which these
      methods should be used.

PMID- 7584255
TI  - Stroke and ischemia.
AB  - With the introduction of diffusion imaging the diagnosis and acute stroke can be
      made within minutes of clinical onset. In combination with perfusion imaging,
      tissue viability can be assessed. The etiology of ischemia can in most cases be
      investigated by MR angiography. The current applications of these techniques are
      reviewed, and pitfalls as well as problems in the diagnosis of acute stroke are
      discussed. With the availability of these techniques, patients can almost
      instantaneously be approved for pharmacotherapy and monitored and thus clinical
      outcome potentially can be improved tremendously.

PMID- 7584256
TI  - MR angiography flow analysis. Neurovascular applications.
AB  - The ability to directly measure velocity and volume flow rates adds a new
      dimension to the MR angiographic evaluation of patients with cerebrovascular
      disease. Reduced volume flow rates are associated with flow restrictive stenoses.
      Flow volumes begin to drop when the area of the vessel lumen is reduced by
      greater than 80%. Cerebrovascular flow reserve also can be determined by
      obtaining volume flow measurements before and after the administration of a
      vasodilator such as acetazolamide. Recent applications include the investigation
      of the flow dynamics associated with subclavian steal, aneurysms, and
      arteriovenous malformations.

PMID- 7584257
TI  - The importance of cue familiarity and cue distinctiveness in prospective memory.
AB  - Both retrospective cued-memory tasks and event-based prospective memory tasks
      require that cue and target information be associated, and that aspects of that
      association be reinstated for successful remembering. These functional
      similarities between retrospective memory and prospective memory were the bases
      for the hypothesis that the familiarity and the distinctiveness of the target
      event (cue) would influence prospective memory performance. Experiment 1,
      focusing on target familiarity, found a nominal advantage in prospective memory
      with unfamiliar target events. Experiment 2 showed a significant benefit for
      unfamiliar target events, as well as for target events that were distinctive
      relative to the local context. Additionally, prospective memory performance did
      not reliably correlate with explicit retrospective memory tasks (recall and
      recognition), but did correlate with an indirect retrospective memory task (word
      fragment completion). This pattern suggests and helps specify the general view
      that prospective memory processes may be similar to those involved in both direct
      and indirect tests of retrospective memory.

PMID- 7584258
TI  - Similarity as an organising principle in short-term memory.
AB  - The role of stimulus similarity as an organising principle in short-term memory
      was explored in a series of seven experiments. Each experiment involved the
      presentation of a short sequence of items that were drawn from two distinct
      physical classes and arranged such that item class changed after every second
      item. Following presentation, one item was re-presented as a probe for the
      'target' item that had directly followed it in the sequence. Memory for the
      sequence was considered organised by class if probability of recall was higher
      when the probe and target were from the same class than when they were from
      different classes. Such organisation was found when one class was auditory and
      the other was visual (spoken vs. written words, and sounds vs. pictures). It was
      also found when both classes were auditory (words spoken in a male voice vs.
      words spoken in a female voice) and when both classes were visual (digits shown
      in one location vs. digits shown in another). It is concluded that short-term
      memory can be organised on the basis of sensory modality and on the basis of
      certain features within both the auditory and visual modalities.

PMID- 7584259
TI  - Forgotten variables in memory theory and research.
AB  - Memory research, like other scientific research, disregards many variables in
      order to bring the full force of the scientific method to bear on clearly
      important variables. The reasons why memory research attends to certain variables
      and disregards others emanate largely from theoretical assumptions that
      distinguish memory systems from other psychological systems, and that distinguish
      variables intrinsic to memory from those extrinsic to memory. Nevertheless, a
      number of these 'forgotten' variables affect memory performance. Regardless of
      past practice, it is a mistake for memory research to continue to ignore relevant
      variables. Doing so introduces measurement error that contaminates memory
      performance measures, and classification error that precludes the discovery of
      legitimate memory variables. It is proposed here that if forgotten memory
      variables are controlled, manipulated, and measured more extensively, then future
      memory research will have greater power and memory theories will have greater
      validity.

PMID- 7584260
TI  - A developmental deficit in short-term phonological memory: implications for
      language and reading.
AB  - QU, an eight-year-old boy, was identified from a large scale normative study on
      the basis of his greatly reduced digit span, combined with normal long-term
      memory and non-verbal intelligence. Further investigation indicated that his
      visual STM was normal, but that he was clearly impaired on two verbal STM tests,
      nonword repetition, and memory span for words. His span showed clear effects of
      phonological similarity and word-length, suggesting qualitatively normal
      functioning of the phonological loop component of working memory, despite a
      quantitative impairment in level of performance. This pattern resembles that
      found in an earlier study of children with a specific language disorder. We
      tested QU on measures of vocabulary, syntax, and reading, and found him to be
      substantially below the age norms on all three. The implications of these
      findings are discussed for the role of the phonological loop in language
      development.

PMID- 7584263
TI  - Misinformation and warnings in eyewitness testimony: a new testing procedure to
      differentiate explanations.
AB  - Although psychologists agree that the presentation of misleading post-event
      information often results in errant recollections, there is disagreement about
      the explanation as to why this occurs. Some (cf. Loftus, Donders, Hoffman, &
      Schooler, 1989) believe this misinformation alters the memory trace created by
      the original information, whereas others (cf. McCloskey & Zaragoza, 1985) have
      argued that the data do not necessitate this explanation. An experiment, designed
      to differentiate the various explanations, was conducted. Its critical elements
      were: (1) a condition with a specific warning presented immediately after the
      misleading information; and (2) a ranking procedure used at testing. The results
      suggest multiple traces may exist for a limited period, but not indefinitely.

PMID- 7584262
TI  - Perceptual and conceptual cueing in implicit and explicit retrieval.
AB  - Subjects saw or heard words in a list (e.g. limerick) and then took two
      successive tests. The first was a yes/no recognition test in which
      auditory/visual modality of test words was manipulated orthogonally to the study
      modality. The second test varied with experimental conditions: subjects produced
      words to either perceptual (fragment) cues (l- -e-ick) or conceptual cues (What
      name is given to a lighthearted five-line poem?), under either explicit or
      implicit retrieval instructions. The major findings were: (a) that regardless of
      the type of retrieval cue (perceptual or conceptual) the degree of dependency
      between recognition and cued recall was greater than that between recognition and
      implicit retrieval; and (b) that modality shifts adversely affected perceptually
      cued explicit and implicit retrieval, whereas they had no effect either on
      conceptually cued retrieval or on recognition. These results suggest that the
      memory system subserving, and the processes involved in, conceptual priming
      differ from those underlying recognition and perceptual priming.

PMID- 7584261
TI  - Recollecting naturally-occurring intentions: a study of cognitive and affective
      factors.
AB  - This paper is concerned with the recall of naturally-occurring intentions during
      the interval between their formulation and their enactment, hours, days, or
      months later. When these intentions were spontaneously recalled, subjects
      recorded the prevailing cognitive and affective circumstances, and current events
      and actions. This task was undertaken for a period of five consecutive days. A
      subsequent task elicited similar information from the same subjects, on randomly
      sampled occasions that did not coincide with the recall of an intention, during a
      comparable time period. The results indicate that on occasions on which subjects
      report these spontaneous recollections, they often judge themselves to be
      concentrating less on a concurrent activity that requires less attention,
      compared to occasions on which behaviour is randomly sampled. The results suggest
      also that this prototypical 'recollective state' may vary with the type of
      intention that is recalled. The advantages and disadvantages of the methodology
      adopted in this study for research on prospective memory processes are
      considered.

PMID- 7584264
TI  - Does inhibition spread in a manner analogous to spreading activation?
AB  - Two experiments explored limited capacity inhibitory selective attention
      processes in working memory. Experiment 1 used a modified Sternberg-type 'short
      term memory scanning' task, where both irrelevant and relevant memory-set words
      were included to see if an inhibitory fan effect operated on lexical associates
      of the should-be-ignored (irrelevant) words. Experiment 2 used a 'negative
      priming' task, where a target letter to be named was flanked by one, two, or
      three distractor letters to see if an inhibitory fan effect operated on the
      should-be-ignored letters. Results from both experiments supported the existence
      of a limited capacity spreading inhibition counterpart to spreading activation.
      The findings were discussed in terms of a model recently proposed by Neumann and
      DeSchepper (1991; 1992) in which two selective attention subprocesses (one
      excitatory and one inhibitory) in the brain each maximise opposed functions
      within their respective resource limitations in working memory.

PMID- 7584266
TI  - The generalisability of confidence-accuracy studies in eyewitnessing.
AB  - This paper discusses the evidence on the confidence-accuracy relationship in
      eyewitness research. It is pointed out that the conclusion often drawn on the
      basis of such research, that there is little or no relationship between
      eyewitness confidence and accuracy, is an unwarranted generalisation based on the
      use of experimental paradigms that are limited in terms of their generalisability
      to courtroom situations. In particular, almost all studies involve between
      subject rather than within-subject designs, thereby limiting the generalisability
      of findings. A within-subjects analysis examines whether, within an individual,
      more confident responses are associated with greater accuracy than are less
      confident responses. A between-subjects analysis examines whether a more
      confident individual is likely to be more accurate than a less confident
      individual. A further limitation on the generalisability to real life situations
      of studies conducted to date is that experiments must involve making errors in
      identification in order to allow correlational analysis to take place. This means
      that findings cannot be generalised to those real life situations where all
      subjects are likely to be completely accurate and confident.

PMID- 7584267
TI  - An ecological study of professors' memory for student names and faces: a
      replication and extension.
AB  - This experiment measured university professors' memory for the names and faces of
      current and former students over a two-semester span. If courses function as
      contextual retrieval cues for professors to remember their students, the passing
      of each semester should diminish the distinctiveness of these cues. Based on the
      Bruce and Young (1986) model of face recognition, we hypothesised that as
      contextual cues become less distinctive, performance should suffer more on name
      recall tests than on name or face recognition tests. We found that name free
      recall and portrait-cued name recall declined very sharply after one semester (6
      months), and face recognition declined after two semesters (12 months), whereas
      name recognition remained perfect. These results provide a general replication
      and extension of Bahrick (1984), and show that difficulties in recalling names
      cannot be due to any weakening of name representations in memory. We suggest that
      name recall may be dependent on contextual cues that become less distinctive with
      succeeding semesters.

PMID- 7584265
TI  - Field and observer modes of remembering.
AB  - Nigro and Neisser (1983) contrasted two ways of remembering personal experiences:
      the rememberer may 'see' the event from his or her perspective as in normal
      perception, or 'see' the self engaged in the event as an observer would. Several
      factors contribute to the determination of perspective, but Nigro and Neisser
      also reported that many subjects claimed they could change to another perspective
      at will. We sampled personal memories from several life periods and assessed
      ability to change the initially reported perspective. Changing was easier for
      recent or vividly recalled events, harder for older and less vividly recalled
      events. Memory perspectives may differ in other aspects than their imagery. A
      second study was conducted to determine whether affective experience is altered
      when perspectives are changed. The affect experienced decreased when shifting
      from a field to an observer perspective, but did not change with the converse
      shift. These studies provide further evidence that remembering is more than
      retrieval. The information that enters awareness is determined by the information
      sources in memory and the organisational scheme adopted for recollection.

PMID- 7584269
TI  - Mathematical constraints and the Tulving-Wiseman law: a rejoinder.
AB  - Hintzman (1991; 1992) has claimed that the reason data points approximate the
      recognition failure function discovered by Tulving and Wiseman (1975) is that
      they are mathematically constrained to do so, and the reason that a few data
      points do not approximate the function, but are exceptions to it, is that these
      data points are less subject to mathematical constraints. He has additionally
      argued that such exceptions are more likely with low levels of recall and strong
      underlying sources of positive covariance. We provide empirical evidence relevant
      to this mathematical model using 301 observations from a database of all relevant
      experimental conditions published between 1973 and 1992 (Nilsson & Gardiner,
      1993). We conclude that mathematical constraints have only a minor influence on
      the function, not the causal role assigned to them in Hintzman's (1992) model. By
      our account, both the function and exceptions to it reflect a single
      psychological principle, the functional effectiveness of contextual cues.

PMID- 7584268
TI  - Priming effects in prospective memory.
AB  - The objective of this study was to examine whether an increased activation of
      knowledge structures facilitates memory for future actions. Priming effects were
      manipulated by giving subjects a category fluency task for half of the target
      categories used in the subsequent prospective memory task. In this task, younger
      and older adults performed an action whenever an instance of a given semantic
      category occurred in the context of a free association task. The degree of
      retrieval support was varied by using typical and atypical category instances as
      targets. Although reliable priming effects were observed for both age groups, the
      magnitude of priming interacted with the degree of retrieval support. Older
      adults showed priming effects for typical targets only, whereas the opposite
      pattern of results was obtained for younger adults. These findings indicate that,
      in addition to retrieval-related factors, the operations performed at the time of
      planning also contribute to optimal prospective remembering.

PMID- 7584270
TI  - On the origin of functional differences in recollective experience.
AB  - Subjects studied target words that were repeated either immediately (lag0) or
      after six intervening items (lag6). At retention testing, subjects were required
      to discriminate targets from distractors and, contingent on a 'yes' response, to
      classify each identified item as one that evoked either a 'remember' (R) response
      or a 'know' (K) response. An R response indicated recognition based on conscious
      recollection, and K, recognition without conscious recollection. R responses were
      significantly greater in lag6 than lag0 whereas the reverse was found for K
      responses. The data are interpreted as showing that R responses depend on the
      probability of a target stimulus engaging conscious effortful processing, whereas
      K responses are increased in the absence of conscious involvement at learning.

PMID- 7584271
TI  - Memory for proper names: a review.

PMID- 7584273
TI  - Selective preservation of place names in an aphasic patient: a short report.

PMID- 7584272
TI  - Production of proper names: a clinical case study of the effects of phonemic
      cueing.
AB  - The production of proper names is a task that in everyday life is particularly
      prone to temporary failures, especially in elderly subjects. The reason for this
      is still rather obscure but indications in recent literature suggest an
      independent status for proper names in comparison with common ones, which may
      entail differences in processing or in processing demands. The main sources of
      empirical evidence come, on the one hand, from studies of face and person
      identity recognition and, on the other, from neuropsychological observations. All
      the findings appear to concur in supporting theoretical distinctions that have
      been made for a long time in the field of philosophy of language. These
      distinctions have directed the endeavours of experimental research. The present
      study describes, for the first time, a neuropsychological patient who shows, in
      certain conditions, a sparing of proper names despite an otherwise deeply
      troubled linguistic production. This finding may appear to be counterintuitive,
      considering the fact that proper names are viewed, in general, as more difficult
      to produce than common ones. However, in consideration also of other emerging
      neuropsychological and experimental findings, it is proposed that possible
      differences in lexical access for the two categories of common and proper names
      may explain the phenomenon and still be consistent with mainstream philosophical
      theories.

PMID- 7584274
TI  - Spared written naming of proper nouns: a case report.
AB  - In this study we describe an investigation into the residual written word
      retrieval skills of M.E.D., a patient with a severe aphasia. M.E.D.'s performance
      on written naming and writing to dictation tasks showed a distinctive pattern of
      performance across semantic categories. The patient's ability to write the names
      of countries and famous people was consistently superior to her ability to write
      the names of objects. These results could be considered as indicative of a double
      dissociation in the proper nouns category, as there are already patients on
      record who have a selective deficit in retrieving proper nouns.

PMID- 7584275
TI  - Selective preservation of a lexical category in aphasia: dissociations in
      comprehension of body parts and geographical place names following focal brain
      lesion.
AB  - The selective dissociation of memory for proper names is discussed in the context
      of a review of dissociations involving broadly defined vs narrowly defined
      semantic categories in brain damaged adults. Two narrowly defined categories for
      which dissociations have been reported are body parts (selectively impaired in
      comprehension) and geographical place names (selectively preserved in
      comprehension). In this study, 167 aphasic patients were tested for their ability
      to correctly identify body parts and map locations from spoken names, relative to
      a baseline for correct responses on general word discrimination (object
      identification). Wernicke's aphasics and Global aphasics both had significantly
      more success in pointing to named map locations and significantly worse
      performance in pointing to named body parts than they had in selecting other
      objects from multiple choice. Anomic aphasics showed precisely the opposite
      pattern of results. Other aphasic subgroups (Broca's aphasics, Mixed Nonfluent
      aphasics, Conduction aphasics, Transcortical Motor and Transcortical Sensory
      aphasics, and Mixed Fluent aphasics) did not show significant deviations in
      either direction. We suggest that the selective preservation for place names may
      be related to their status as proper names.

PMID- 7584276
TI  - Repetition priming and proper name processing. Do common names and proper names
      prime each other?
AB  - Three experiments are reported in which a repetition priming technique was used
      to investigate whether recognition of a person's surname which is also a known
      word (e.g. Baker) activates the lexical representation that mediates word
      recognition. Experiment 1 showed that a familiarity decision to familiar full
      names produced an effect of repetition priming on subsequent lexical decision to
      words that were presented in the initial task as surnames. Experiment 2
      demonstrated that, conversely, a lexical decision primed subsequent familiarity
      decision to full names involving the same word. Experiment 3 showed that
      repeating the same decision during the initial and test phases did not produce a
      larger repetition priming effect than that obtained when the task at test
      differed from the prime task (name familiarity decision vs lexical decision or
      vice versa). The results are interpreted as support for the view that repetition
      priming is due to repeated activation of representations that are accessed by
      both common names and proper names.

PMID- 7584277
TI  - Retrieval failures in face naming.
AB  - Several authors have reported that the incidence of retrieval failures is higher
      for people's names than for object names. The first aim of the paper was to
      evaluate the role of one factor that might contribute to making face naming
      difficult. Face naming usually requires the retrieval of one specific label: the
      name of the seen individual. Object naming is less restricting. First, object
      names may have synonyms. Second, labels available from different levels of
      categorisation of an object may be appropriate to name that object (e.g.
      trousers, jeans, Levis). Such a degree of freedom does not exist in naming faces.
      The hypothesis that face naming is made difficult by the simple fact that people
      have only one name was tested by studying faces having the exceptional property
      of bearing two names: faces of actors playing nameable characters (e.g. Harrison
      Ford playing Indiana Jones). Consistent with the hypothesis, data from two
      experiments showed that when bypassing a block is possible by producing another
      name that is known for a face, the incidence of blocks falls dramatically. The
      other aim of the paper was to test the reversed frequency effect in person naming
      reported previously in several diary studies, in an experimental setting. A
      direct frequency effect rather than a reversed frequency effect was obtained in
      the present study.

PMID- 7584278
TI  - Access to visual information from a name is contingent on access to identity
      specific semantic information.
AB  - In this study, we investigated subjects' ability to retrieve information about a
      familiar person's facial appearance in response to seeing their name. Each famous
      name was associated with one of four occupations (sport, music, politics, and
      acting) and one of four distinctive facial features (beard, long hair, glasses,
      baldness). Subjects were asked to state which occupation, and which facial
      feature was associated with each name. The most important finding was that
      subjects were generally only able to recall the distinctive facial feature that a
      person possessed if they were also able to recall their occupation. Recall of the
      person's occupation, by contrast, was not contingent on remembering the person's
      facial appearance. These results suggest that there are no direct links between
      the representation of a person's name in memory and visual information about
      their facial appearance. The link appears to be indirect, and to be mediated by
      non-visual semantic information about the person, such as their occupation. This
      conclusion was also supported by an examination of the effects of biographical
      cues on subjects' ability to recall facial information that they had previously
      failed to recall. In a second experiment, subjects were presented with
      biographical details about famous people, and were asked to retrieve information
      about their face and name. Retrieval of facial information did not appear to be
      contingent on recall of the name, nor did recall of the name appear to be
      contingent on retrieval of facial information. On the basis of the results, an
      hierarchical model of name recognition is presented which is analogous to current
      models of face recognition (e.g. Bruce & Young, 1986).

PMID- 7584279
TI  - Spontaneous mnemonic strategies used by older and younger adults to remember
      proper names.
AB  - Little attention has been focused on the spontaneous mnemonic strategies that
      people use to remember proper names. In the experiment reported here, groups of
      younger (< 25 years old) and older subjects (> or = 55 years old) were shown a
      series of 12 name-face pairs and instructed to remember them. In a subsequent
      test, they were shown the same faces and asked to recall the corresponding names.
      After the recall task, subjects completed a questionnaire about the mnemonic
      strategies they used. Our analyses revealed not only that the younger subjects
      recalled more names than did the older subjects, but also that older and younger
      subjects reported using certain strategies more frequently than other strategies.
      Moreover, regression analyses indicated that use of certain mnemonic strategies
      accounted for a significant proportion of recall performance beyond that
      accounted for by age alone. Older-old subjects (> or = 70 years old) recalled
      fewer names than did younger-old subjects (> or = 55 and < 70 years old), but
      they did not differ in the extent to which they used specific mnemonic
      strategies. Our results suggest that the use of spontaneous mnemonic strategies
      may play a role in the difference in proper name recall between younger and older
      adults.

PMID- 7584280
TI  - The difficulty with recalling people's names: the plausible phonology hypothesis.
AB  - Recalling the name of a person is a simple, but often a problematic, everyday
      task. There are various explanations of this phenomenon, but here it is argued
      that the explanations offered so far, by failing to consider learning of names,
      have overlooked a simple account of name recall difficulty. The starting
      observation for this viewpoint is that names of people are often non-words, in
      that they have never been encountered before. This is not true of, say, names of
      professions. Not only does the relatively high rate of new exemplars mean that
      people's names are likely to be underlearned, but furthermore, even for equal
      degrees of learning, a person's name is at a disadvantage because of the high
      plausibility of most phonologies: "dreaner" is much more readily accepted as the
      name of a person than as the name of their profession. So specifying the
      phonology of people's names is inherently a more demanding task, compared to the
      phonology of other names. The implications of this view are explored with regard
      to explanations of empirically established name recall phenomena in normal
      subjects, the patterns of performance of anomic patients and the difficulty of
      name recall in different word domains. It is shown that these arguments, derived
      from a real world fact, account in a simple way for existing data and make
      predictions in different areas of research.

PMID- 7584282
TI  - Naming faces and naming names: exploring an interactive activation model of
      person recognition.
AB  - In this paper we present an interactive activation and competition (IAC) model of
      name recognition. This is an extension of a previous account of name retrieval
      (Burton & Bruce, 1992) and is based on a functional model due to Valentine,
      Bredart, Lawson, and Ward (1991). Several empirical effects of name recognition
      are simulated: (1) names that are known are read faster than names that are
      unknown; (2) common names are read faster than rare names; and (3) rare names are
      recognised as familiar faster than common names. The simulations demonstrate that
      these complex effects can arise as a natural consequence of the architecture of
      the IAC model. Finally, we explore a modification of the Valentine et al.
      functional model, and conclude that the model as originally proposed is best able
      to account for the available data.

PMID- 7584281
TI  - Proper names and how they are learned.
AB  - Proper names function in our conceptual lives as means for denoting individuals
      in kinds. Kinds are denoted by common names, more precisely count nouns, and so
      there are important interrelations between proper names and common nouns. All of
      this shows up in the way we interpret proper names and employ them in everyday
      inferences. For example, an airline may count three passengers in relation to a
      single person Jane, if Jane takes three trips with the airline. Each of the three
      passengers is Jane, but there is only one Jane. To handle such operations we
      propose a theory of proper names as part of the theory of kinds. This enables us
      to specify certain resources (some of them unlearned) that are necessary for the
      learning of proper names and also a theory of how they are learned. We review the
      experimental literature on the learning of proper names from the standpoint of
      the theory. We do not extend the theory to cover recognition or recall.

PMID- 7584283
TI  - Involuntary conscious memory and the method of opposition.
AB  - Priming in an indirect test of stem completion should reflect involuntary memory,
      but can be accompanied by conscious awareness of the past (involuntary conscious
      memory) or unaccompanied by such awareness (involuntary unconscious memory). We
      adapted the method of opposition developed by Jacoby, Woloshyn, and Kelley (1989)
      to obtain a measure of stem-completion priming that should reflect only
      involuntary unconscious memory. Subjects completed stems with the first word
      coming to mind, but wrote down a different word if the word that came to mind
      first had been previously encountered. Facilitatory priming was expected only
      when involuntary unconscious influences outweighed inhibitory effects of
      involuntary conscious memory, or of intentional retrieval. We observed a
      facilitation effect for items processed graphemically at encoding, in conjunction
      with an inhibition effect for items processed semantically at encoding. In
      contrast, a standard indirect test showed similar levels of priming following
      graphemic and semantic encoding, whereas a direct test showed a strong advantage
      of semantic over graphemic encoding. We argue that the two encoding activities
      produced approximately equivalent involuntary influences of memory, but that
      items encoded semantically were associated with involuntary conscious memory to a
      greater extent than were items encoded graphemically. Comparing indirect and
      opposition test performance can provide a quantitative index of relative levels
      of involuntary conscious and involuntary unconscious memory.

PMID- 7584284
TI  - Effects of practice on tip-of-the-tongue states.
AB  - Tip-of-the-tongue (TOT) states were examined in relation to acquisition
      manipulations, using named imaginary animals (TOTimals) as targets. High levels
      of TOT states were found in three experiments. In the first experiment an
      increase in the duration of initial exposure to target material improved recall
      and recognition, and reduced the number of unrecalled items not in TOT states
      (NTOTs), but did not affect TOT levels. In Experiment 2 practice at writing
      target names, as compared with only reading them, improved recall performance and
      decreased TOT levels, but did not reduce NTOTs. Experiment 3 replicated the
      finding that writing during practice reduced TOT states, but did not reduce
      NTOTs, and also found that more frequent practice trials increased recall without
      affecting TOT levels. The results suggest that practice writing target names
      prevents TOT states by strengthening otherwise deficient phonological connections
      in memory, a deficiency that can cause TOT states when visual-to-lexical
      connections give only partial access to a target in memory. The results also
      demonstrate the usefulness of the TOTimal technique for testing effects of
      acquisition variables on TOT experiences.

PMID- 7584285
TI  - Autobiographical memory and daily schemas at work.
AB  - This exploratory study examines how daily schemas for work activities influence
      retrospective memory. Twelve subjects were asked to describe their 'typical day'
      at work, and to recall their work activities of yesterday and of the same day a
      week ago. The number of basic activities occurring in each description was
      counted, and the number of basic activities occurring in the typical day
      description was viewed as an index of the degree of elaboration of the schema.
      There were three major findings. First, people recalled fewer activities from
      last week than they did from yesterday, and those activities that were recalled
      from last week tended to be those that were in the daily schema. Second, there
      was a tendency for people with highly elaborated daily schemas to recall more
      activities from last week than people with poorly elaborated schemas. And third,
      there were more schematic references in the recalls from last week than in those
      from yesterday. Taken together, these findings indicate that there are strong
      schematic influences on the recall of activities from last week, but not on those
      from yesterday. The discussion points to a number of research issues, both
      applied and theoretical, which arise from this preliminary investigation of daily
      work schemas.

PMID- 7584286
TI  - Why are there sometimes concreteness effects in memory for prose?
AB  - Four experiments explored on-line encoding strategies and memory for high imagery
      and low imagery texts. Results consistently indicated that concreteness effects
      in memory for text depend on how materials are presented in several different
      respects. Most importantly, the experiments clarified apparently contradictory
      results of previous studies by indicating that concreteness effects generally do
      not occur in memory for prose when imageability is manipulated between-subjects,
      and that their occurrence when imageability is manipulated within-subjects
      depends on the order occurrence when imageability is manipulated within-subjects
      depends on the order of presentation. In addition, moving window analyses of text
      processing strategies indicated that differential strategies observed in previous
      studies when subjects listened to high vs low imagery text do not generalize to
      reading of the same materials. Potential explanations for the pattern of results
      are evaluated, and implications for theories of mental imagery and memory are
      considered.

PMID- 7584287
TI  - The Children's Test of Nonword Repetition: a test of phonological working memory.
AB  - This article presents findings from the Children's Test of Nonword Repetition
      (CNRep). Normative data based on its administration to over 600 children aged
      between four and nine years are reported. Close developmental links are
      established between CNRep scores and vocabulary, reading, and comprehensive
      skills in children during the early school years. The links between nonword
      repetition and language skills are shown to be consistently higher and more
      specific than those obtained between language skills and another simple verbal
      task with a significant phonological memory component, auditory digit span. The
      psychological mechanisms underpinning these distinctive developmental
      relationships between nonword repetition and language development are considered.

PMID- 7584288
TI  - Assessment of long-term verbal memory in children.
AB  - This study was designed to evaluate the use of a Paired Associate Learning Test
      (PALT) and a Story Recall test with children aged from 8 to 12 years. 46 normal
      control children and 19 children of low ability were given the PALT from the
      Wechsler Memory Scale, and a story recall task, based on Wechsler's Logical
      Memory subtest, but using stories designed to be suitable for children.
      Performance on PALT approached ceiling levels for the control children. Both PALT
      and story recall were more strongly correlated with measures of verbal ability
      than with digit span. Reliable measures of immediate story recall can be obtained
      using two or three stories. Many children who are unable to recall a story after
      a 45 minute delay show dramatic improvement when given a single cue, and it is
      argued that cued delayed recall gives a better index of long-term memory than
      uncued recall. Correlations between immediate recall and cued delayed recall are
      high, and the data presented here may be used to compute a forgetting score which
      takes into account the level of immediate recall. In the sample seen here, rate
      of forgetting was remarkably constant across individuals, in both normal and low
      ability individuals. It is concluded that memory deficits affecting rate of
      forgetting are rare, but that the test materials described here could be useful
      for identifying such disorders in children with neurological impairments.

PMID- 7584289
TI  - The Extended Rivermead Behavioural Memory Test: a measure of everyday memory
      performance in normal adults.
AB  - The Rivermead Behavioural Memory Test provides a well-validated instrument for
      detecting everyday memory problems in patient groups. It was however designed as
      a screening test, and thus is insufficiently sensitive to detect mild deficits,
      whether due to brain damage or to the introduction of a drug or stressor. The
      Extended Rivermead Behavioural Memory Test (ERBMT) increases the level of
      difficulty by doubling the amount of material to be remembered, by combining
      material from Forms A and B, and Forms C and D of the original test to produce
      two parallel versions of the new extended test. The sensitivity of the ERBMT was
      assessed by comparing the performance of a middle-aged and an elderly group of
      normal subjects, who would be expected to show modest differences in memory
      performance. The subtests varied in their sensitivity to this small age
      difference, but when performance was assessed in terms of scaled scores that
      allow an overall combined measure of memory performance to be calculated, the
      test proved sensitive (t = 4.87, P < 0.0001), and free of ceiling and floor
      effects. We suggest that the ERBMT provides a promising measure of everyday
      memory in normal adults.

PMID- 7584290
TI  - Four easy memory tests for older adults.
AB  - This report describes four short memory tests which have been developed for use
      with older adults. Three of these tests are recognition memory tests; one is
      verbal, one is visual, and one is predominantly visual, but likely to involve
      some verbal mediation. The fourth task is a verbal paired-associate learning test
      which uses two sets of six high frequency words. Normative data obtained from 107
      subjects aged 64-81 on all four tests are provided. A ceiling effect was
      obtained, indicating that these tests are relatively easy. A validation study was
      carried out, in which a group of patients with a cortical degenerative condition
      was assessed on the easy tests, and performance on published recognition memory
      tests could be compared with performance on the easy tests. Several patients who
      had scored at chance on the published version not only obtained measurable scores
      on the easy version, but also obtained discrepancy scores. Possible uses for the
      four short memory tests are suggested.

PMID- 7584292
TI  - The Autobiographical Memory Interview (AMI) in organic and psychogenic amnesia.
AB  - The Autobiographical Memory Interview (AMI) is a semi-structured interview,
      sampling a subject's recollections across three broad time-periods. In patients
      with organic amnesia or dementia, there is an impairment in recalling both
      autobiographical facts and incidents, and there is a temporal gradient such that
      early memories are relatively spared. Correlations with measures of anterograde
      memory are relatively low, and lesions affecting the frontal lobes, anterior
      temporal poles, the posterior-medial temporal lobes, or even projections from the
      occipital lobes, can impair retrieval of autobiographical memories. In
      schizophrenia, an impairment in retrieving autobiographical incidents, comparable
      with organic amnesia, has been reported in some patients. However a patient with
      delusional memories secondary to schizophrenia is cited, in whom AMI performance
      was normal. Finally, patients with psychogenic amnesia show a variable pattern of
      performance, but, in general, there is a disproportionate impairment of
      autobiographical memory, and often an anomalous temporal gradient, which can
      recover subsequently.

PMID- 7584293
TI  - Memory tools for the researcher and clinician.

PMID- 7584291
TI  - Two tests for assessing remote public knowledge: a tool for assessing retrograde
      amnesia.
AB  - Guidelines for the construction and development of tests of remote memory are
      provided. These guidelines follow from methodological considerations and from
      certain theoretical issues we believe that remote memory tests should address if
      they are to further our understanding of amnesia. These include: the pattern of
      temporal gradient; memory for different broad classes of information such as
      famous names and famous events; and recall and recognition of different types of
      detail such as contextual and non-contextual information associated with remote
      memory. With respect to the first of these, we argue that it is impossible to
      fully evaluate competing hypotheses about temporally graded retrograde amnesia
      unless items are selected from at least two difficulty levels, and from at least
      two time periods. The construction of two equivalent tests of remote memory, one
      for famous people, the other for famous events, is described, and the theoretical
      issues listed earlier were addressed using these tests in a study comparing the
      remote memory of 13 organic amnesics and 13 age- and IQ-matched controls. The
      principal findings were as follows. There was only weak evidence that amnesics'
      remote memory for famous people and events was temporally graded over a 20 year
      period, and recognition memory and memory for non-contextual detail were equally
      impaired. Mayes, Meudell, and Pickering's (1985) context memory deficit
      hypothesis was supported, however, because amnesics were more impaired in their
      ability to date recognised items. In addition, although there was little support
      for a temporally graded retrograde impairment on the recognition question, there
      was much clearer evidence for the temporal dating question. Also, one patient,
      SR, showed a selective deficit in dating recognised names and events from the
      1980s. Finally, the correlations between measures of anterograde and retrograde
      amnesia were all non-significant. Suitable items for the construction of remote
      memory tests probing the four decades 1950s to 1980s are presented. A subset of
      these, from the 1970s and 1980s, were shown to have satisfactory psychometric
      qualities, and can therefore be recommended for more widespread clinical use,
      although more extensive normative data than that provided here will be necessary.

PMID- 7584294
TI  - No selective deficit in recall in amnesia.
AB  - Are amnesic patients selectively impaired in recall relative to recognition?
      Experiment 1 studied a group of Korsakoff amnesics and matched the amnesic level
      of recognition with that of control subjects by testing control recognition of
      unrelated words after longer delays. It was found that under these conditions the
      observed levels of recall were also approximately equal. In Experiment 2, a
      similar result occurred when the Korsakoff amnesic level of recognition for
      unrelated words was matched by varying the number of presentations as well as
      delay before testing. In Experiment 3, a similar result occurred again with a
      group of amnesics of mixed aetiology and recognition levels for related words
      matched by varying the duration of presentation and delay before testing. In this
      experiment, both recognition and recall of the same items were assessed. It was
      found that for the amnesic group the observed level of dependency between
      recognition and recall was less than that for the control group. One possible
      interpretation of this result is that the microstructure of the recall process
      may be selectively disturbed in amnesia. The principal finding, however, is that
      in all three experiments there was no significant evidence of the existence in
      amnesia of a selective deficit in the overall level of recall relative to that of
      recognition.

PMID- 7584295
TI  - Identifying the basis for the word frequency effect in recognition memory.
AB  - Recent theories of recognition memory have identified two bases on which
      recognition-memory judgments may be made: recollection, which involves retrieval
      of contextual information from an earlier episode of stimulus presentation; and
      familiarity, which is distinguished by a general sense of familiarity in the
      absence of recollection. Four experiments were conducted to test whether the word
      frequency effect (WFE) in recognition memory (superior performance with low- in
      comparison with high-frequency targets) results from recollection-based
      processes, familiarity-based processes, or both. In two of the experiments,
      superior memory for aspects of the study context was found for low-frequency in
      comparison with high-frequency words, suggesting frequency-related differences in
      recollection. The other two experiments used Jacoby's (1991) inclusion/exclusion
      paradigm to provide estimates of the contribution of recollection and familiarity
      to recognition. In both experiments the data suggested that the WFE is primarily
      a recollection-based phenomenon. These findings suggest that the recognition
      memory WFE for old items results primarily from the effects of word frequency on
      recollection. The implications of these findings for theories of recognition
      memory are discussed.

PMID- 7584297
TI  - Auditory priming in elderly adults: impairment of voice-specific implicit memory.
AB  - Previous research has shown that elderly adults often exhibit intact priming
      effects on visual implicit memory tests, but little is known about auditory
      priming and ageing. We examined priming effects on auditory stem-completion and
      filter identification tasks in older and younger adults. Young subjects showed
      more priming when speaker's voice was the same as study and test than when it
      differed, but elderly subjects failed to exhibit this voice-specific priming
      effect in each of five experiments. The elderly did, however, show robust
      nonspecific priming. We attempt to rule out hearing deficit accounts of the
      priming impairment and consider alternative theoretical interpretations of the
      effect.

PMID- 7584298
TI  - Norms of paired-associate recall during multitrial learning of Swahili-English
      translation equivalents.
AB  - No normative data have been available for the recall of recently studied foreign
      language vocabulary items. We report data from 200 university undergraduates who
      had three study-recall trials on Swahili-English translation equivalents (e.g.
      ardhi-soil). Performance on each of the three study-recall trials is reported for
      each of the 100 items. Recall varied from near-zero to near-perfect across the
      combinations of items and trials, thereby allowing investigators to choose
      combinations of items and trials that will produce any desired range of recall
      difficulty. Substantial improvements in recall of the items occurred across study
      test trials, and therefore the items seem suitable both for investigations of the
      effect of acquisition variables and for most of the other goals that are
      satisfied by laboratory paired-associate items.

PMID- 7584296
TI  - Recognition and recall-like processes in the long-term reconstruction of order.
AB  - Four experiments examined whether the recovery of an item's position in a
      sequence taps processes similar to recognition and/or recall. Across the
      experiments, subjects either recalled, recognised, or made position judgements
      about list items that differed in word frequency. Typical word frequency effects
      were found in recall and recognition, but frequency failed to affect measures of
      position memory consistently across the four experiments. Despite the apparent
      procedural similarities across tasks, it appears that the recovery of position
      information may tap mnemonic processes that are different from those tapped by
      recognition and recall. Implications of these findings for current models of
      position memory are discussed.

PMID- 7584299
TI  - Very long-term recall in infants: infantile amnesia reconsidered.
AB  - Subjects who had participated in a study on non-verbal recall before their first
      birthday returned to the laboratory one year later and were tested for recall of
      their previous visit. During their previous visit they had shown recall of both
      familiar and novel actions on a set of novel objects. However, after a year's
      delay, evidence for recall was found for the familiar actions only. One action in
      particular was responsible for this finding: feeding a teddy bear with a
      schematic bottle. The majority of the returning subjects who had been shown this
      action repeated it after a year, whereas none of the other returning subjects and
      few of the subjects in the control groups performed this action. The results
      indicate that young infants have the ability to recall an event both at 11 months
      of age and after a delay as long as one year. The finding that infants can recall
      during a period that later becomes inaccessible to memory is important to our
      understanding of infantile amnesia.

PMID- 7584300
TI  - After 8 months have passed: long-term recall of events by 1- to 2-year-old
      children.
AB  - The time course of development of the ability to remember specific past events is
      a matter of considerable curiosity and debate. Traditional and contemporary
      theories alike suggest that infants are unable to consolidate and stabilise event
      knowledge for recall after a long time period. In two experiments, we used
      elicited imitation, a nonverbal analogue to cued verbal recall, to test 21-, 24-,
      and 29-month-old children's recall of events they had experienced eight months
      previously. At the time of original exposure some of the events were novel,
      whereas others depicted activities familiar to 1-year-olds. At the eight-month
      retention test, performance of the experienced children was compared to that of
      matched naive controls. In both experiments the experienced children produced a
      greater number of the novel events; there were no differences between the groups
      on the familiar events. The results demonstrate long-term recall of specific past
      events by 1- to 2-year-olds. They thus challenge the suggestion that the absence
      of memories from infancy and early childhood is attributable to the inability to
      form memories that are enduring and accessible over time.

PMID- 7584301
TI  - Fifty months of memory: a longitudinal study in early childhood.
AB  - Three studies were conducted to evaluate long-term memory longitudinally. In
      Study 1, 10-month-olds (N = 20) were taught to operate a toy in their homes and
      were tested at home after four months, as were age-matched (14 months)
      inexperienced controls (N = 20). Experienced infants were more willing to remain
      in the play situation, relearned faster than controls, and one operated the toy
      spontaneously. In Study 2, conducted 18 months thereafter, two subgroups (N = 5)
      of Study 1 groups and an age-matched (32 months) control group (N = 5) were
      observed in a lab playroom. Only the children with experiences at both 10 months
      and 14 months operated the toys without being shown. Children with a single 14
      month experience made equivalent numbers of toy contacts and successful
      responses, however, and both groups exceeded controls. In Study 3, conducted 2+
      years after Study 2, 36 children played in a novel playroom. Subgroups differed
      in amount and timing of experience (in Studies 1 and 2); a naive age-matched (60
      months) control group (N = 6) was added. Controls took longer to make the toy
      work than children in the combined experience groups. Only experienced children
      elected to operate the toys later in the session. Two children verbally recalled
      part of the 10-month event. The findings are discussed in the light of their
      relevance to the assessment and description of memory during early childhood.

PMID- 7584306
TI  - Professional practice and role diversity: a team concept for patient
      transportation systems.
AB  - Critical care nurses providing interhospital transportation services face new
      challenges in structuring a professional practice model in a diverse role
      environment. Nurses are now finding themselves working together with a variety of
      health care professionals with different educational and experience levels. This
      article discusses the program development and shared governance development of
      one such interhospital transportation team. Shared governance in a unique
      environment such as this was achieved using a functional model (self-directed
      work teams) and several outcome-focused components that are described in detail.
      The difficulties encountered with the introduction of a governance structure are
      also shared as too are the resolutions. With the changing health care system and
      the evolving changes in critical care nursing roles, innovation is fundamental to
      patient care practices. Shared governance does have a place in nurse/nonnurse
      amalgamations.

PMID- 7584305
TI  - How to make professional practice models work.
AB  - Professional practice models and shared governance have had much attention
      recently. They have been credited with being the answer to nurse retention,
      advancing the nursing profession, expanding nursing roles, and increasing
      autonomy for practice and work life. This article describes strategies for
      implementing and maintaining a professional practice model. Organizational
      support, nurse manager role change, unit readiness, salaried compensation, and
      incentives are areas that must be assessed before implementing a model. The
      models described are unit based and use the concepts of shared governance and
      group practice.

PMID- 7584304
TI  - Long-term retention of memory for preverbal experience: evidence and
      implications.

PMID- 7584302
TI  - Three-year-olds remember a novel event from 20 months: evidence for long-term
      memory in children?
AB  - Thirty-seven 3-year-old children, who had learned a 9-action event sequence
      ("making Play-Doh spaghetti") when they were 20 months old, returned to the lab
      to determine whether they would be able to verbally and/or behaviourally recall
      the event after a 12- to 22-month delay. Children originally participated in the
      event either one or three times and experienced different parts of the event
      either at three distinct locations (spatial condition) or at a single location
      (nonspatial condition). Results show very little evidence of long-term memory for
      the event after one to two years. Returning children did not verbally recall the
      event, and they did not perform more actions or sequence the event more
      accurately than controls, with the exception of the older experimental children
      who had a tendency to sequence the event more accurately than same-aged controls.
      Although the results indicate that young children's memory for novel events is
      not very enduring, there were individual differences in children's ability to
      remember the event. These differences are discussed in terms of potential
      differences in cognitive abilities and changing knowledge about retrieval
      strategies or memory.

PMID- 7584303
TI  - Reactivation of toddlers' event memory.
AB  - Toddlers of 14 and 18 months learned to produce target actions for six
      activities, were allowed to forget their training, and were reminded of the
      activities 8 or 10 weeks later, depending on their age. Reminders were
      administered in a memory-reactivation paradigm in which toddlers were shown the
      target actions of three of the six activities but were not allowed to imitate the
      modelled actions. Toddlers were tested for their recall of all six activities 24
      hours after the reactivation treatment. Toddlers who were passively exposed to
      three activities during the reactivation session recalled more activities than
      controls who either were not reminded or did not originally engage in the
      activities. This study reveals that 14- and 18-month-olds encode components of an
      event associatively and that they are able to remember seemingly forgotten
      components through passive re-exposure to other components of the event.

PMID- 7584307
TI  - Focus on autonomy: supporting an innovative, empowered staff.
AB  - Current nursing literature documents the benefits of nurse autonomy with evidence
      of increased job satisfaction. Health care organizations can support autonomous
      behavior through empowerment. This article reports how one hospital is responding
      to nurses' requests for empowerment. The request to focus the nursing division's
      efforts to enable an innovative empowered staff was initiated during an annual
      planning session with clinical and administrative staff participation. The first
      phase of the project involved baseline measurements of autonomy and strategic
      planning for empowerment through education and leadership modeling. Initial
      autonomy studies were conducted in 1994 and will be repeated at 18, 36, and 48
      months.

PMID- 7584308
TI  - A cardiovascular intensive care nursing staff response to managed care: a change
      in practice.
AB  - Managed care has brought competition to the health care workplace. This
      competitive atmosphere creates challenges to attain quality outcomes while
      minimizing costs. A large community hospital in the mid-Atlantic region, in a
      collaborative effort with all members of the health care team, undertook the
      challenge to revise the way care was delivered to the cardiac surgical patient.
      This article will report the changes the cardiovascular intensive care nursing
      staff had to undergo and the methods that were used to incorporate these changes.

PMID- 7584309
TI  - Peer review: an approach to performance evaluation in a professional practice
      model.
AB  - Role expectations of staff nurses are changing, and nurses must become empowered
      and actively involved in facilitating that change, rather than having their role
      changed for them. The shared governance framework provides an efficient way to
      meet current changes and increased responsibilities. Peer review is an integral
      component of this framework. A professional practice model with peer review
      increases the accountability of its members by encouraging improved work
      achievement and reinforcing high standards of practice. Promoting communication
      and sharing of each individual's practice enhances a sense of teamwork and
      encourages creativity and an increased sense of ownership regarding nursing
      practice among all model members.

PMID- 7584310
TI  - Evolution of peer review: enhancing communication through team review.
AB  - Few institutions have successfully implemented peer review. It is considered a
      hallmark of the nursing profession and in theory has positive effects by
      stimulating personal and professional development and challenging nurses to think
      critically about their practice. The key is that the change must be managed, unit
      readiness assessed, and an implementation plan developed. It is suggested that
      all members of the critical care team be involved in the review process.
      Characteristics of a unit that is ready to implement team review are presented
      and discussed.

PMID- 7584314
TI  - Differences in professional practice model outcomes: the impact of practice
      setting.
AB  - Over the past several years, involvement strategies such as professional practice
      models and shared governance strategies have been implemented in a variety of
      nursing practice settings. This article reviews the results of a secondary
      analysis of an evaluation of a professional practice model at a large academic
      medical center. This review compares critical care and general acute care nurses
      in terms of their perceptions of and satisfaction with work in a professional
      practice environment and identifies and contrasts significant predictors of
      general job satisfaction and turnover intent within the two groups. Implications
      of differences in outcomes in different settings are explored.

PMID- 7584311
TI  - The successful utilization of nonlicensed assistive staff in a critical care
      area.
AB  - Health care organizations are under public and political pressure to control
      costs, produce quality outcomes, and have high client/patient satisfaction
      levels. To reduce costs and capitalize on the talents and skills of professional
      nurses, a variety of organizational redesigns, reengineerings, and new role
      creations are taking place. This article explores the use of nonlicensed
      assistive/supportive staff in a critical care unit. The focus includes the
      salient objectives for the use of assistive/supportive staff, as well as criteria
      for decisions and design and a developmental model for role development.

PMID- 7584312
TI  - Satisfaction with a new model of professional practice in critical care.
AB  - Although only a moderately severe general nursing shortage exists at this time,
      the shortage of critical care nurses remains severe. Innovative administrators
      across the country are trying new professional practice models aimed at
      maximizing autonomy and freeing nurses from mundane tasks with the hopes of
      retaining experienced clinicians. We implemented a professional practice model in
      which unlicensed assistive personnel were trained to assist registered nurses in
      patient care. Monies saved by increasing nurse-patient ratios were distributed to
      staff nurses. Acuity-based staffing was maintained and professional practice
      encouraged through self-scheduling and elimination of hierarchical relationships.
      Satisfaction among nurses working in the program increased in terms of coworkers
      and supervision. Patient satisfaction with the quality of care provided did not
      change during the course of the program. Data from interviews demonstrated that
      staff were satisfied with the quality of care provided by the assistants, but the
      changes in the staffing ratios coupled with the increased responsibility for
      overseeing the assistants caused stress in the nurses. We conclude that a
      professional practice model in which critical care assistants are added to the
      work force is a viable option, but creative methods of addressing the stress of
      increased workload are needed.

PMID- 7584313
TI  - Increasing job satisfaction and motivation while reducing nursing turnover
      through the implementation of shared governance.
AB  - In today's cost-conscious, changing health care environment, health care agencies
      must identify and implement strategies to promote fiscal responsibility while
      maintaining employee satisfaction and retention. The cost to recruit professional
      nurses is high. Therefore, the business objective is to retain the productive
      employee. Through the implementation of shared governance, employees find the
      workplace rewarding and stimulating--motivating factors as described by Herzberg.
      The Secretary's Commission on Nursing identified 16 strategies for the reduction
      of the nursing shortage and retention of professional nurses. One recommendation
      reinforces a report by the American Academy of Nursing that states work
      satisfaction among nurses in higher and turnover rates lower when organizational
      climates provide for nursing's involvement in decision making relating not only
      to nursing practice and unit management but also patient care. Through shared
      governance, staff nurse involvement in nursing and patient care policy is
      advanced.

PMID- 7584315
TI  - The clinical nurse specialist role in shared governance.
AB  - In the current health care environment, changes in organizational structure and
      care delivery systems are occurring in an effort to improve quality, efficiency,
      and customer satisfaction while decreasing cost. Shared governance empowers the
      staff to help facilitate these changes. The clinical nurse specialist (CNS) is a
      key person in facilitating and maintaining the shared governance environment.
      This new facet of the role makes the CNS a valuable resource and is instrumental
      in helping the organization achieve its goals. This article addresses the CNS's
      role in the initiation and continuation of shared governance within the nursing
      department.

PMID- 7584317
TI  - Characterization of proteoglycan accumulation during formation of cartilagenous
      tissue in vitro.
AB  - In order to study proteoglycan retention and accumulation, we optimized a
      chondrocyte cell culture system in which isolated bovine articular chondrocytes
      accumulate extracellular matrix to form a continuous layer of cartilagenous
      tissue. The tissue can attain a thickness of up to 110 microns by 35 days. The
      cells synthesize large keratan sulfate containing proteoglycans and type II
      collagen indicating that the chondrocytes maintain their phenotype in these
      culture conditions. Matrix accumulation is enhanced by increased cell density and
      the presence of serum and ascorbic acid. The amount of proteoglycans synthesized
      by the chondrocytes increases up to day 21 and then decreases to the same levels
      as are synthesized during the first week of culture. The percentage of newly
      synthesized proteoglycans retained in the matrix increases from 20% on day 6 to a
      maximum of 85% by day 35. The proteoglycan and collagen content in the tissue
      increases with time in culture. The changes in the percentage of proteoglycans
      retained parallels the increase in proteoglycan content. After day 35, there is
      no further increase in the amount of proteoglycans and collagen nor in the
      percentage of newly synthesized proteoglycans retained in the extracellular
      matrix. These studies demonstrate that the cultures are going through two phases:
      one of matrix accumulation and then one of maintaining the existing matrix. The
      period of matrix accumulation occurs between days 10-21 whereas matrix
      maintenance is observed after day 35. Using this culture system to study
      proteoglycan accumulation and maintenance during these culture periods may prove
      useful in identifying the mechanisms regulating these processes.

PMID- 7584318
TI  - Effects of transforming growth factor beta on proteoglycan synthesis by cell and
      explant cultures derived from the knee joint meniscus.
AB  - Repair of meniscal tears depends in part upon the ability of the resident
      fibrochondrocytes to produce new extracellular matrix molecules including
      proteoglycans. Three culture systems have been used to investigate proteoglycan
      production by meniscal fibrochondrocytes from the inner, middle and outer zones
      of medial and lateral menisci of the sheep stifle joint. Cultures of meniscal
      explants, monolayered cells, and cells encapsulated in alginate beads were
      labeled with 35SO4H2 for 48 h in the absence and presence of transforming growth
      factor beta (TGF beta) and the proteoglycans were analysed by Sephacryl S-1000
      chromatography. In general, the lateral meniscus produced more proteoglycan than
      the medial. Explants from the inner and middle zones produced predominantly
      aggrecan-like proteoglycan, together with a smaller proteoglycan population
      eluting with an average distribution coefficient of around 0.65. The outer
      meniscal zones synthesized less proteoglycan overall, the majority of which
      consisted of the smaller proteoglycans. These characteristic proteoglycan size
      profiles obtained with explant cultures also were preserved when cells isolated
      from the respective zones were cultured in alginate beads. Monolayer cell
      cultures, however, produced almost entirely small proteoglycans, regardless of
      their zone of origin. Chromatography of chondroitinase AC and ABC digested
      samples indicated that the small proteoglycan population comprised mostly
      dermatan sulphate-containing proteoglycans. In all meniscal zones and in all
      culture systems, TGF beta stimulated proteoglycan production by up to 100% and
      the proteoglycans were slightly larger. TGF beta also stimulated cell division in
      fibrochondrocyte monolayer cultures. Long term intermittent stimulation of
      alginate bead cultures with TGF beta resulted in large increases in proteoglycan
      synthesis, increased aggregation of large proteoglycan monomers, and an increase
      in the production of the larger of two small proteoglycans, putatively, biglycan.

PMID- 7584319
TI  - Efficacy of traditional Chinese acupuncture in the treatment of symptomatic knee
      osteoarthritis: a pilot study.

PMID- 7584320
TI  - Recommended methodology for assessing the progression of osteoarthritis of the
      hip and knee joints.

PMID- 7584316
TI  - Biosynthesis and characterization of type X collagen in human fetal epiphyseal
      growth plate cartilage.
AB  - We examined in vitro collagen biosynthesis by organ cultures from human fetal
      epiphyseal growth plate cartilage. The biosynthetic products were characterized
      by NaCl fractional precipitation, limited proteolytic digestion, and sodium
      dodecyl sulfate-polyacrylamide slab gel electrophoresis. Organ cultures of human
      fetal epiphyseal growth plate cartilage synthesized large amounts of type X
      collagen in addition to type II, type IX, and type XI collagens. The individual
      polypeptide chains of human type X collagen migrated with an apparent M(r) of 45
      kDa after proteolytic digestion with pepsin. The migration pattern of these
      molecules did not change when examined under reducing and nonreducing conditions,
      indicating that they did not contain intrahelical disfulfide bonds. Comparison of
      the rates at type X collagen biosynthesis at weeks 20 and 24 of human fetal
      development showed a marked increase of 24 weeks. Northern hybridization analysis
      of total RNA from freshly isolated epiphyseal growth plate chondrocytes with a
      cDNA corresponding to the carboxyl terminus of human type X collagen indicated
      that the developmental increase of type X collagen production is determined by
      pre-translational mechanisms.

PMID- 7584321
TI  - The isolation and characterization of magnesium whitlockite crystals from human
      articular cartilage.
AB  - A number of basic calcium phosphate crystals have been demonstrated in human
      articular tissues. The exact relationship between crystal deposition and disease
      remains obscure, although there is evidence supporting a rapid degenerative
      arthropathy within a specific set of patients. Limited reports of 'cuboid'
      calcium phosphate microcrystals in articular cartilage have been made over the
      last 10 years. In this study the occurrence of such crystals, not apparent by
      light microscopy, in human articular cartilage has been confirmed by transmission
      electron microscopy and X-ray microanalysis of tissue prepared by aqueous and
      anhydrous processing techniques. A crystal isolation technique involving
      collagenase digestion, centrifugation and sodium hypochlorite treatment was
      developed enabling crystal characterization by electron and X-ray diffraction.
      Crystals were identified as magnesium whitlockite; the first report of this
      mineral in articular cartilage. The presence of this mineral phase in normal and
      osteoarthritic articular cartilage is discussed with consideration given to
      physical conditions known to favor whitlockite formation and those extant in
      articular cartilage.

PMID- 7584322
TI  - Articular cartilage proteoglycans in osteoarthritic STR/Ort mice.
AB  - Compared to controls, the lateral and medial tibial articular cartilage
      chondroitin sulfate (CS) content in male STR/Ort mice was elevated between 8 and
      19 weeks of age, fell at 24-26 weeks and increased again thereafter. The CS
      cartilage content of CBA mice remained relatively unchanged. Cartilage CS content
      was measured in female CBA and STR/Ort mice and in male and female Balb C mice,
      all at 18 weeks of age. In every case the content was much lower than that found
      in male STR/Ort mice. CS unsaturated disaccharides were analysed by capillary
      electrophoresis after digestion of the glycosaminoglycans with chondroitinase
      ABC. Chondroitin-4-sulfate (C4S) was the predominant isomer at all ages in both
      strains. The C4S:C6S isomer ratio in CBA mice was much higher in the lateral than
      the medial cartilage. This difference was much less marked in STR/Ort knee
      joints: these mice have relatively more C6S than CBA mice. Proteoglycans,
      extracted from STR/Ort and CBA male mouse cartilage, were characterized by large
      pore gel electrophoresis and Western blotting. All cartilages contained two slow
      mobility bands identified as aggrecan by the reactivity with the mab 1C6. Both
      bands contained C4S and C6S chains. A third band of faster mobility contained
      only C4S and was 1C6 negative. It was present in both strains. Thus the STR/Ort
      cartilage contained a normal spectrum of murine articular cartilage
      proteoglycans.

PMID- 7584324
TI  - Representation for discovery of protein motifs.
AB  - There are several dimensions and levels of complexity in which information on
      protein motifs may be available. For example, one-dimensional sequence motifs may
      be associated with secondary structure identifiers. Alternatively, three
      dimensional information on polypeptide segments may be used to induce
      prototypical three-dimensional structure templates. This paper surveys various
      representations encountered in the protein motif discovery literature. Many of
      the representations are based on incompatible semantics, making difficult the
      comparison and combination of previous results. To make better use of machine
      learning techniques and to provide for an integrated knowledge representation
      framework, a general representation language--in which all types of motifs can be
      encoded and given a uniform semantics--is required. In this paper we propose such
      a model, called a spatial description logic, and present a machine learning
      approach based on the model.

PMID- 7584325
TI  - Protein secondary structure modelling with probabilistic networks.
AB  - In this paper we study the performance of probabilistic networks in the context
      of protein sequence analysis in molecular biology. Specifically, we report the
      results of our initial experiments applying this framework to the problem of
      protein secondary structure prediction. One of the main advantages of the
      probabilistic approach we describe here is our ability to perform detailed
      experiments where we can experiment with different models. We can easily perform
      local substitutions (mutations) and measure (probabilistically) their effect on
      the global structure. Window-based methods do not support such experimentation as
      readily. Our method is efficient both during training and during prediction,
      which is important in order to be able to perform many experiments with different
      networks. We believe that probabilistic methods are comparable to other methods
      in prediction quality. In addition, the predictions generated by our methods have
      precise quantitative semantics which is not shared by other classification
      methods. Specifically, all the causal and statistical independence assumptions
      are made explicit in our networks thereby allowing biologists to study and
      experiment with different causal models in a convenient manner.

PMID- 7584327
TI  - Probabilistic structure calculations: a three-dimensional tRNA structure from
      sequence correlation data.
AB  - Algorithms based on probability theory can address issues of uncertainty directly
      through their representational framework and their theory for data combination.
      In this paper, we discuss the advantages of probabilistic formulations for
      molecular-structure calculations, describe one implementation of such a
      formulation, and show its performance on a data set derived from analysis of the
      statistical correlations within a set of aligned transfer RNA sequences. By
      assigning reasonable physical interpretations to certain statistical
      correlations, we are able to calculate three-dimensional structures for tRNA from
      a random starting structure. The constraints that we use are associated with
      different variances, and so their effects are not uniform, and must be reconciled
      by a probabilistic algorithm to yield the most likely structure. As might be
      predicted, the uncertainty in the position for each base is a function of both
      the number and strength of the constraints, and is reflected in the variances in
      atomic position calculated by the algorithm. For example, the hinge region in the
      tRNA is shown to be the most uncertain. In addition, the algorithm retains
      information about positional covariation that is useful for understanding the
      relationships between different parts of the structure. These experiments also
      demonstrate that we can define a single-sphere representation for each base that
      is useful for nucleic acid structural calculations in the same way that alpha
      carbon representations are useful for protein structural calculations.

PMID- 7584323
TI  - Proceedings of the 1st International Conference on Intelligent Systems for
      Molecular Biology. ISMB--93.

PMID- 7584326
TI  - Comparison of two variations of neural network approach to the prediction of
      protein folding pattern.
AB  - We have designed, trained and tested two types of neural networks for the
      prediction of protein folding pattern from sequence. Here we describe the
      differences in the networks and compare their performance on a variety of
      proteins. Both network representations are generally successful in predicting
      protein fold and can also be used together to confirm a prediction.

PMID- 7584328
TI  - Protein classification using neural networks.
AB  - We have recently described a method based on Artificial Neural Networks to
      cluster protein sequences into families. The network was trained with Kohonen's
      unsupervised-learning algorithm using, as inputs, matrix patterns derived from
      the bipeptide composition of the proteins. We show here the application of that
      method to classify 1758 protein sequences, using as inputs a limited number of
      principal components of the bipeptidic matrices. As a result of training, the
      network self-organized the activation of its neurons into a topologically ordered
      map, in which proteins belonging to a known family (immunoglobulins, actins,
      interferons, myosins, HLA histocompatibility antigens, hemoglobins, etc.) were
      usually associated with the same neuron or with neighboring ones. Once the
      topological map has been obtained, the classification of new sequences is very
      fast.

PMID- 7584329
TI  - Pattern recognition for automated DNA sequencing: I. On-line signal conditioning
      and feature extraction for basecalling.
AB  - The massive scale of DNA sequencing for the Human Genome Initiative compels
      efforts to reduce the cost and increase the throughput of DNA sequencing
      technology. Contemporary automated DNA sequencing systems do not yet meet
      estimated performance requirements for cost-effective and timely completion of
      this project. Greater accuracy of basecalling software would minimize manual
      review and editing of basecalling results, and facilitate assembly of primary
      sequences to large contig(uous) arrays. In this report we describe a neural
      network model for photometric signal conditioning during raw data acquisition
      with an automated DNA sequencer. This network supports on-line extraction and
      evaluation of informative arrays of oligomer separations and yields, as a feature
      table for accurate, real-time basecalling.

PMID- 7584331
TI  - Integrating order and distance relationships from heterogeneous maps.
AB  - There is no automatic mechanism to integrate information between heterogeneous
      genome maps. Currently, integration is a difficult, manual process. We have
      developed a process for knowledge base design, and we use this to integrate order
      and distance relationships between genetic linkage, radiation hybrid, and
      physical maps. Until now, the only way to develop a persistent, knowledge
      intensive application was to either develop a new knowledge base from scratch or
      coerce the application to fit an existing knowledge base. This was not from lack
      of interest by the knowledge base or database community, but merely from a lack
      of theoretical tools powerful enough to tackle the problem. We import formalisms
      from knowledge representation, natural language semantics, programming language
      research, and databases. These form a strong, theoretical foundation for
      knowledge base design upon which we have implemented the knowledge base design
      tool called WEAVE.

PMID- 7584330
TI  - A modular learning environment for protein modeling.
AB  - We propose in this paper a modular learning environment for protein modeling. In
      this system, the protein modeling problem is tackled in two successive phases.
      First, partial structural informations are determined via numerical learning
      techniques. Then, in the second phase, the multiple available informations are
      combined in pattern matching searches via dynamic programming. It is shown on
      real problems that various protein structure predictions can be improved in this
      way, such as secondary structure prediction, alignment of weakly homologous
      protein sequences or protein model evaluations.

PMID- 7584334
TI  - Grammatical formalization of metabolic processes.
AB  - In the field of biotechnology and medicine it is of interest to model and
      simulate metabolic processes. The usual methods to model metabolic pathways are
      chemical descriptions and differential equations. Moreover, the graph theoretical
      aspect is discussed and the development of expert systems is in process. In this
      paper we present the formalization of metabolic processes. Our formalization is
      based on the theory of formal languages. This formalization is called genetic
      grammar and represents an expansion of the Semi-Thue-System.

PMID- 7584333
TI  - PALM--a pattern language for molecular biology.
AB  - This paper presents a new pattern language, PALM, for describing patterns in
      molecular biology sequences. The language is intended for representing knowledge
      about such patterns in a declarative, clear and concise way. It is also shown
      that its expressive power enables the definition of any regular or context free
      language, and also higher languages in the Chomsky hierarchy by parameter
      attachment, variables and procedural attachment. It is also possible to define
      approximate patterns. The language is rigorously defined, and several examples of
      its use and expressive power are given.

PMID- 7584332
TI  - Inference of order in genetic systems.
AB  - We survey and discuss issues required of intelligent systems to support research
      efforts in locus mapping. In particular we focus on the issues of order, on how
      one can automate the reasoning processes of ordering, and the database structures
      required to support orders, including ambiguity and uncertainty. We conclude with
      a summary of work to be done.

PMID- 7584335
TI  - Finding relevant biomolecular features.
AB  - Many methods for analyzing biological problems are constrained by problem size.
      The ability to distinguish between relevant and irrelevant features of a problem
      may allow a problem to be reduced in size sufficiently to make it tractable. The
      issue of learning in the presence of large numbers of irrelevant features is an
      important one in machine learning, and recently, several methods have been
      proposed to address this issue. A combination of machine learning approaches and
      statistical analysis methods can be used to identify a set of relevant attributes
      for currently intractable biological problems. We call our framework F/I/E (Focus
      Induce-Extract). As an example of this methodology, this paper reports on the
      identification of the features of mutations in collagen that are likely to be
      relevant in the bone disease Osteogenesis imperfecta.

PMID- 7584336
TI  - Constructive induction and protein tertiary structure prediction.
AB  - To date, the only methods that have been used successfully to predict protein
      structures have been based on identifying homologous proteins whose structures
      are known. However, such methods are limited by the fact that some proteins have
      similar structure but no significant sequence homology. We consider two ways of
      applying machine learning to facilitate protein structure prediction. We argue
      that a straightforward approach will not be able to improve the accuracy of
      classification achieved by clustering by alignment scores alone. In contrast, we
      present a novel constructive induction approach that learns better
      representations of amino acid sequences in terms of physical and chemical
      properties. Our learning method combines knowledge and search to shift the
      representation of sequences so that semantic similarity is more easily recognized
      by syntactic matching. Our approach promises not only to find new structural
      relationships among protein sequences, but also expands our understanding of the
      roles knowledge can play in learning via experience in this challenging domain.

PMID- 7584337
TI  - Representations of metabolic knowledge.
AB  - Construction of electronic repositories of metabolic information is an
      increasingly active area of research. Encoding detailed knowledge of a complex
      biological domain requires finely honed representations. We survey
      representations used for several metabolic databases, including Eco-Cyc, and
      reach the following conclusions. Representation of the metabolism must
      distinguish enzyme classes from individual enzymes, because there is not a one-to
      one mapping from enzymes to the reactions they catalyze. Individual enzymes must
      be represented explicitly as proteins, e.g., by encoding their subunit structure.
      The species variation of metabolism must be represented. So must the substrate
      specificity of enzymes, which may be treated in several ways.

PMID- 7584339
TI  - Protein sequencing experiment planning using analogy.
AB  - Experiment design and execution is a central activity in the natural sciences.
      The SeqER system provides a general architecture for the integration of automated
      planning techniques with a variety of domain knowledge in order to plan
      scientific experiments. These planning techniques include rule-based methods and,
      especially, the use of derivational analogy. Derivational analogy allows planning
      experience, captured as cases, to be reused. Analogy also allows the system to
      function in the absence of strong domain knowledge. Cases are efficiently and
      flexibly retrieved from a large casebase using massively parallel methods. The
      SeqER system is initially configured to plan protein sequencing experiments.
      Planning is interleaved with experiment execution, simulated using the SequenceIt
      program. SeqER interacts with a human user who analyzes the data generated by
      laboratory procedures and supplies SeqER with new hypotheses. SeqER is a vehicle
      in which to test theories about how scientists reason about experimental design.

PMID- 7584338
TI  - Database techniques for biological materials & methods.
AB  - The Biological sciences produce an enormous research literature every year.
      Research papers are highly structured documents whose content is not captured
      using the traditional techniques of information retrieval: keywords and flat
      text. This is especially true of the Materials & Methods section of experimental
      papers. A great deal of highly structured information is packed into this
      section. It involves logical and temporal sequences of operations that combine
      and operate on materials using various instruments and depending on many
      parameters. We are designing and implementing databases that will allow this
      complex knowledge to be represented, stored in object-oriented databases and
      retrieved. We are developing an application of this technology called the
      Laboratory Notebook. This application is a software system that will contain
      personal laboratory information as well as have access to databases of Materials
      & Methods sections drawn from the literature.

PMID- 7584341
TI  - Design of an object-oriented database for reverse genetics.
AB  - We present the design of an object-oriented database system for reverse genetics
      applications. Such a database will encapsulate not only the data in the genetic
      and physical maps, but also the methods used to create the maps as well as
      methods to link them to other databases, such as GenBank, PIR, and MedLine. The
      purpose of this database is to provide the fungal genetics community with an
      electronic tool for identifying the biochemical function of any DNA fragment in
      the database--electronic reverse genetics. Such a tool for reverse genetics will
      enable researchers to identify the biochemical functions associated with genes
      encoding proteins in fungal development pathways, purine metabolism, the heat
      shock response, and molecular chromosome mechanics and evolution. Our initial
      goal is to apply the database for the genome mapping of the filamentous fungi,
      Aspergillus nidulans and Neurospora crassa, at the University of Georgia and the
      University of Leeds in England.

PMID- 7584340
TI  - Detection of correlations in tRNA sequences with structural implications.
AB  - Using an flexible representation of biological sequences, we have performed a
      comparative analysis of 1208 known tRNA sequences. We believe we our technique is
      a more sensitive method for detecting structural and functional relationships in
      sets of aligned sequences because we use a flexible representation (for
      sequences), as well as a general statistical method that can detect a wide range
      of relationships between positions in a sequence. Our method utilizes functional
      classifications of the sequence building-blocks (nucleotide bases and amino
      acids) based on physical or chemical properties. This flexibility in sequence
      representation improves the significance of finding sequence relationships
      mediated by the defining property. For example, using a purine/pyrimidine
      classification, we can detect base-stacking interactions in sets of nucleotide
      sequences that form base-paired helices. We use several statistical measures,
      including chi 2-tests, Monte Carlo simulations and an information measure to
      detect significant correlations in sequences. In this paper we illustrate our
      method by analyzing a set of tRNA sequences and showing that the correlations our
      program discovers, in each case, correspond to the known base-pairing and higher
      order interactions observed in tRNA crystal structures. Furthermore, we show that
      novel and interesting features of tRNAs are detected when sequence correlations
      with the charged amino acid (and anticodon) are evaluated. This technique is a
      powerful method for predicting the structure of RNAs and for analyzing specific
      functional characteristics.

PMID- 7584342
TI  - A small automaton for word recognition in DNA sequences and its application to
      consensus analysis of regulatory elements in DNA regions controlling gene
      expression.
AB  - A method for pattern analysis of DNA sequence data is considered. A space
      economical automaton for word recognition was presented elsewhere together with
      an algorithm for its compilation in linear time. An algorithm for the
      localization of words including imperfect matches (motif search) was developed. A
      program was implemented on the Macintosh and used extensively for the
      representation of the word composition of DNA data. We explore different sets of
      regulatory sequences to illustrate the performance of this method. In mammalian
      DNA, this analysis reveals "consensus motifs" corresponding to functional (or
      putative) cis-acting elements mediating the regulation of gene expression.

PMID- 7584343
TI  - Protein secondary structure prediction using two-level case-based reasoning.
AB  - We have developed a two-level case-based reasoning architecture for predicting
      protein secondary structure. The central idea is to break the problem into two
      levels: first, reasoning at the object (protein) level, and using the global
      information from this level to focus on a more restricted problem space; second,
      decomposing objects into pieces (segments), and reasoning at the internal
      structures level; finally, synthesizing the pieces back to the objects. The
      architecture has been implemented and tested on a commonly used data set with
      69.3% predictive accuracy. It was then tested on a new data set with 67.3%
      accuracy. Additional experiments were conducted to determine the effects of using
      different similarity matrices.

PMID- 7584344
TI  - MultiMap: an expert system for automated genetic linkage mapping.
AB  - With the advent of the Human Genome Project, the ability to rapidly construct
      comprehensive and accurate linkage maps based on genetic marker data from family
      studies is an absolute necessity. In addition to their usefulness in localizing
      genes for both simple and complex disorders, linkage maps are invaluable tools
      for genetic counseling using linked marker genes. Several computer program
      packages are publicly available which aid in the construction of linkage maps by
      computing multipoint likelihoods for specified locus orders. However, these
      programs work in a step-by-step fashion, requiring intensive user-intervention
      and analysis at each step. Such a repetitive process is amenable to computerized
      automation. We have developed and tested an expert system computer program,
      MultiMap, for automated genetic linkage mapping. This program greatly reduces the
      amount of user-computer interaction, increasing the accuracy and speed with which
      a map can be constructed. In addition, because the total mapping time is greatly
      reduced through automation, it is now feasible to explore and compare various
      mapping heuristics and mapping criteria in order to develop the most appropriate
      approach, or set of approaches, for genetic linkage mapping. MultiMap need not be
      restricted to the construction of genetic maps, but could be adapted to aid in
      the automated construction of physical maps as well.

PMID- 7584346
TI  - Identification of localized and distributed bottlenecks in metabolic pathways.
AB  - The usual thermodynamic evaluation, based solely on the Standard Gibbs Energy of
      reaction, does not take into account the permissible ranges of concentrations of
      metabolites, and it faces further difficulties when, instead of isolated
      reactions, we are examining whole pathways. For pathways, we seek not only to
      decide whether they are feasible but also to pinpoint the pathway segment that
      causes any thermodynamic difficulties. We define a set of scaled quantities which
      reformulate the thermodynamic-feasibility problem for the whole pathway. We
      present an algorithm which analyzes individual reactions and selective
      construction of larger subpathways and uncovers localized and distributed
      thermodynamic bottlenecks of the biotransformation. This type of thermodynamic
      treatment contributes to the effort to include more physical, chemical, and
      biological factors in the computer-aided analysis of metabolic pathways.

PMID- 7584345
TI  - Constructing a distributed object-oriented system with logical constraints for
      fluorescence-activated cell sorting.
AB  - This paper describes a fully distributed biological-object system that supports
      FACS (Fluorescence Activated Cell Sorter) instrumentation. The architecture of
      the system can be applied to any laboratory automation system that involves
      distributed instrument control and data management. All component processes of
      FACS (such as instrument control, protocol design, data analysis, and data
      visualization), which may run on different machines, are modeled as cooperatively
      working "agents." Communication among agents is performed through shared-objects
      by triggered methods. This shared-object metaphor encapsulates the details of
      network programming. The system facilitates the annotation of classes with first
      order formulae that express logical constraints on objects; these constraints are
      automatically maintained upon updates. Also, the shared-object communication and
      polymorphic triggered methods are exploited to produce a homogeneous interface
      for instrument control.

PMID- 7584347
TI  - Discovering sequence similarity by the algorithmic significance method.
AB  - The minimal-length encoding approach is applied to define concept of sequence
      similarity. A sequence is defined to be similar to another sequence or to a set
      of keywords if it can be encoded in a small number of bits by taking advantage of
      common subwords. Minimal-length encoding of a sequence is computed in linear
      time, using a data compression algorithm that is based on a dynamic programming
      strategy and the directed acyclic word graph data structure. No assumptions about
      common word ("k-tuple") length are made in advance, and common words of any
      length are considered. The newly proposed algorithmic significance method
      provides an exact upper bound on the probability that sequence similarity has
      occurred by chance, thus eliminating the need for any arbitrary choice of
      similarity thresholds. Preliminary experiments indicate that a small number of
      keywords can positively identify a DNA sequence, which is extremely relevant in
      the context of partial sequencing by hybridization.

PMID- 7584348
TI  - The induction of rules for predicting chemical carcinogenesis in rodents.
AB  - This paper presents results from an ongoing effort in applying a variety of
      induction-based methods to the problem of predicting the biological activity of
      noncongeneric (structurally dissimilar) chemicals. It describes initial
      experiments, the long-term goal of which is to assist toxicologists, cancer
      researchers, regulators, and others to predict the toxic effects of chemical
      compounds. We describe a series of experiments in tree and rule induction from a
      set of example chemicals whose carcinogenicity has been determined from long-term
      animal studies, and compare the resulting classification accuracy with eight
      published human and computer predictions for a common set of 44 test chemicals.
      The accuracy of our system is comparable to the most accurate human expert
      prediction yet published, and exceeds that of any of the computer-based
      predictions in the literature. The induced rules provide confirmation of current
      expert heuristic knowledge in this domain. These early results show that an
      inductive approach has excellent potential in predictive toxicology.

PMID- 7584349
TI  - Prediction of primate splice junction gene sequences with a cooperative knowledge
      acquisition system.
AB  - We propose a cooperative conceptual modelling environment in which two agents
      interact: the machine and the human expert. The former is able to extract
      knowledge from data using a symbolic-numeric machine learning system, and the
      latter is able to control the learning process by accepting and validating the
      machine results, or by criticizing those results or the explanation that the
      system produces on them. The improvement of the conceptual modelling relies on
      the cooperation between the two agents. Results obtained with our method on
      prediction of primate splice junctions sites in genetic sequences are far better
      than those reported in the literature with other symbolic machine learning
      systems, and are as better as those obtained with some artificial neural networks
      methods reported at present. But in opposite to neural networks which lack of
      argumentation, our system provides the user a plausible explanation of its
      prediction.

PMID- 7584350
TI  - Knowledge discovery in GenBank.
AB  - We describe various methods designed to discover knowledge in the GenBank nucleic
      acid sequence database. Using a grammatical model of gene structure, we create a
      parse tree of a gene using features listed in the FEATURE TABLE. The parse tree
      infers features that are not explicitly listed, but which follow from the listed
      features. This method discovers 30% more introns and 40% more exons when applied
      to a globin gene subset of GenBank. Parse tree construction also entails
      resolving ambiguity and inconsistency within a FEATURE TABLE. We transform the
      parse tree into an augmented FEATURE TABLE that represents inferred gene
      structure explicitly and unambiguously, thereby greatly improving the utility of
      the FEATURE TABLE to researchers. We then describe various analogical reasoning
      techniques designed to exploit the homologous nature of genes. We build a
      classification hierarchy that reflects the evolutionary relationship between
      genes. Descriptive grammars of gene classes are then induced from the instance
      grammars of genes. Case based reasoning techniques use these abstract gene class
      descriptions to predict the presence and location of regulatory features not
      listed in the FEATURE TABLE. A cross-validation test shows a success rate of 87%
      on a globin gene subset of GenBank.

PMID- 7584351
TI  - A multi-level description scheme of protein conformation.
AB  - We propose a novel description scheme of protein backbone conformation that can
      model the important factors of protein structure formation, such as global
      interaction and geometric constraints. This description scheme represents a
      protein conformation with several symbolic sequences of multiple levels of
      abstraction. Each symbol in the sequence denotes the class of abstracted topology
      of subconformation with the size specific to the level. Low level sequences of
      this description represent fine structures of high resolution, and high level
      sequences represent the abstracted topologies of large scale. The classification
      of protein backbone subconformations of various sizes is the most important base
      for this description scheme. This has never been tried so far due to the
      complexity in dealing with the number of degrees of freedom in subconformations.
      However, the proposed technique solved this problem by abstracting the topology
      of middle and large scale subconformations. This linear expansion technique
      extracts a fixed number of parameters as the expansion coefficients from the co
      ordinate representation of subconformations. In this case, the simple reverse
      transformation from the expansion coefficients reconstructs the three-dimensional
      topology of a subconformation. The analysis of the relation between primary
      structure of a region and the subconformation of that region at each level in
      this description helps to model both local and global interactions of protein
      structure formation. Further, the statistic analysis of overlapping patterns of
      two subconformations models the geometric constraints important for a structure
      prediction system in generating a conformation which is geometrically sound.

PMID- 7584352
TI  - Genetic algorithms for DNA sequence assembly.
AB  - This paper describes a genetic algorithm application to the DNA sequence assembly
      problem. The genetic algorithm uses a sorted order representation for
      representing the orderings of fragments. Two different fitness functions, both
      based on pairwise overlap strengths between fragments, are tested. The paper
      concludes that the genetic algorithm is a promising method for fragment assembly
      problems, achieving usable solutions quickly, but that the current fitness
      functions are flawed and that other representations might be more appropriate.

PMID- 7584355
TI  - Minimizing complexity in cellular automata models of self-replication.
AB  - Understanding self-replication from an information processing perspective is
      important because, among other things, it can shed light on molecular mechanisms
      of biological reproduction and on prebiotic chemical evolution. Intuition,
      biological knowledge, and early computational models of self-replication all
      suggested that self-replication is an inherently complex process. In this paper
      we describe recent computational studies that challenge this viewpoint. We
      summarize our recent work with cellular automata models of simple yet non-trivial
      self-replicating structures called unsheathed loops. For example, one unsheathed
      loop consists of only six components and requires only 20 rules to specify the
      local intercomponent interactions needed to bring about replication. The
      implication of this work is that, when viewed as an emergent property of numerous
      local, concurrent interactions between components, self-replicating systems can
      be substantially simpler than is generally recognized.

PMID- 7584354
TI  - Petri net representations in metabolic pathways.
AB  - The present methods for representing metabolic pathways are limited in their
      ability to handle complex systems, incorporate new information, and to provide
      for drawing qualitative conclusions from the structure of pathways. The theory of
      Petri nets is introduced as a tool for computer-implementable representation of
      pathways. Petri nets have the potential to overcome the present limitations, and
      through a multitude of properties, enable the preliminary qualitative analysis of
      pathways.

PMID- 7584353
TI  - Object-oriented knowledge bases for the analysis of prokaryotic and eukaryotic
      genomes.
AB  - The amount of biological sequences introduced in the general collections, and the
      growing complexity of the biological knowledge require the construction of models
      to formalize this knowledge and particularly the relationships between several
      data types. Two examples of such situations are presented here, they result from
      the biological research lead in our team in the field of molecular evolution.
      ColiGene is a modelling of E. coli genetics devoted to the analysis of
      relationships between genomic sequences and gene expressivity. MultiMap
      implements a new formalization of genome maps allowing manipulation of "maps of
      maps" in two species. Application of ColiGene and MultiMap are not restricted to
      molecular evolution and, for instance, MultiMap offers new capabilities for
      infering data on a genome from knowledge on another species. This could be
      essential for many mapping projects (human, mouse but also other mammals like
      pig). Development and implementation of those models have been done using an
      object-oriented knowledge base management system (SHIRKA) interfaced with a
      dedicated genomic data base management system (ACNUC). Graphical interfaces have
      been designed to give an environment similar to the biological representations
      used by biologists.

PMID- 7584357
TI  - Testing HIV molecular biology in in silico physiologies.
AB  - The natural and medical sciences have strongly benefitted from technological
      advances that help to create and store more raw information than can be
      effectively processed. In particular, this rapid growth has created a strong need
      for a flexible and far-reaching approach to cross-database simulation. The paper
      uses a highly simplified example, called the 'TinyMouse' simulator, to explain
      the design and functioning of interactive cross-database simulators that can be
      applied to prototype experiments with animal models of human disease, such as the
      hu-SCID mouse model for the Acquired Immune Deficiency Syndrome (AIDS). Work in
      progress is discussed to extend 'TinyMouse' into 'CyberMouse', an informational
      organism that synthesizes factual databases of the murine neuroendocrine-immune
      system.

PMID- 7584356
TI  - Building large knowledge bases in molecular biology.
AB  - Large scale genome sequencing projects are now producing hugh amounts of data
      which can be readily stored and managed within data base management systems, and
      analyzed using dedicated software packages. The results of these analyzes should
      also be stored with the input DNA sequences. The increasing complexity and size
      of the objects to be described and managed have led biologists to rely on
      advanced data models such as the object-oriented model. As a joint effort between
      our computer science and molecular biology research projects, the knowledge bases
      we have developed in molecular genetics have shown however that the basic object
      oriented model is not fully adapted to the complexity of some biological
      situations encountered. Advanced descriptive capabilities, provided only by
      knowledge models originated from the AI field, are required. Composite or
      evolving objects, multiple viewpoints, constraints, tasks and methods, textual
      annotations are some examples of such capabilities. They are illustrated by
      biological situations for which they appeared to be necessary. Supporting
      powerful reasoning mechanisms (e.g. object classification, constraint propagation
      or qualitative simulators), they allow the development of large knowledge bases
      in molecular biology. These knowledge bases are expected to become the adequate
      support for co-operative distributed research efforts.

PMID- 7584359
TI  - Identification of human gene functional regions based on oligonucleotide
      composition.
AB  - Accurate recognition of coding and intron regions within large regions of
      uncharacterized genomic DNA is an unsolved problem. A data base of more than
      4,240,791 bp coding and 7,790,682 bp noncoding human sequences was extracted from
      GenBank to develop a function for locating coding regions in anonymous sequences.
      Several coding measures based on oligonucleotide preferences were tested on a
      control set that including 1/3 of all extracted sequences. An accuracy of
      separation of coding/noncoding regions is 87% for 9 bp oligonucleotides on 54 bp
      windows and 91% on 108 bp windows, respectively. For separation of coding/intron
      regions the accuracy is 89-90% for 8 bp oligonucleotides on 54 bp windows and up
      to 95% on 108 bp windows. Using the information about preferences of
      octanucleotides in protein coding and intron regions and significant triplet
      frequencies as a function of position near splice junctions, a joint splice site
      prediction scheme was developed. The accuracy of the joint scheme for predicting
      splice site positions on the test set was about 96-97%, which exceeds the
      accuracy of the previously reported splice site selection method based on a more
      complex artificial neural network approach. A model of splicing using poly-G(C)
      rich exon flanking sequences is suggested. A remarkable difference of
      oligonucleotide composition 5'- and 3'- gene regions is displayed and applied in
      a gene structure predictive system.

PMID- 7584360
TI  - SENEX: a CLOS/CLIM application for molecular pathology.

PMID- 7584358
TI  - A partial digest approach to restriction site mapping.
AB  - We present a new practical algorithm to resolve the experimental data of
      restriction site analysis, which is a common technique for mapping DNA.
      Specifically, we assert that multiple digests with a single restriction enzyme
      can provide sufficient information to identify the positions of the restriction
      sites with high probability. The motivation for the new approach comes from
      combinatorial results on the number of mutually homeometric sets in one
      dimension, where two sets of n points are homeometric if the multiset of (n2)
      distances they determine are the same. Since experimental data contains error, we
      propose algorithms for reconstructing sets from noisy interpoint distances,
      including the possibility of missing fragments. We analyze the performance of
      these algorithms under a reasonable probability distribution, establishing a
      relative error limit of r = theta (1/n2) beyond which our technique becomes
      infeasible. Through simulations, we establish that our technique is robust enough
      to reconstruct data with relative errors of up to 7.0% in the measured fragment
      lengths for typical problems, which appears sufficient for certain biological
      applications.

PMID- 7584361
TI  - A service-oriented information sources database for the biological sciences.
AB  - Researchers in the biological sciences require access to a variety of information
      sources located in various places on different computer networks. In order to
      satisfy the information needs of a researcher, appropriate information sources
      must be selected and access to these information sources and the computing
      services supporting them must be provided in a way that does not distract the
      researcher from problems of real interest. At the University of Missouri-Columbia
      a service-oriented information sources database is being developed as a key
      component of a layered-model design of an intelligent system which will provide a
      research environment appropriate to the needs of researchers in the biological
      sciences.

PMID- 7584362
TI  - Computationally efficient cluster representation in molecular sequence
      megaclassification.
AB  - Molecular sequence megaclassification is a technique for automated protein
      sequence analysis and annotation. Implementation of the method has been limited
      by the need to store and randomly access a database of all the sequence pair
      similarities. More than 80,000 protein sequences are now present in the public
      databases, and the pair similarity data table for the full protein sequence
      database requires over 1 gigabyte of storage. In this paper we present a
      computationally efficient representation of groups based on a graph theory
      approach where sequence clusters are described by a minimal spanning tree of
      highest scoring similarity pairs. This representation allows a classification of
      N proteins to be stored in order(N) memory. The use of this minimal spanning tree
      representation simplifies analysis of groups, the description of group
      characteristics and the manual correction of artifacts resulting from false hits.
      The new tree representation also introduces new possibilities for artifact
      generation in sequence classification. Methods for detecting and removing these
      artifacts are discussed.

PMID- 7584365
TI  - Pattern discovery in gene regulation; designing an analysis environment.
AB  - Interactions that determine cellular fate are exceedingly complex, can take place
      at different levels of gene regulation and involve a large number of components
      (such as genes, proteins). 'Wet lab' biology has an inherent difficulty in
      considering multiple components within one experimental set-up. Thus, the
      individual experimental results may reflect the behavior of a sub-system and be
      missing some important information concerning interactions with other components.
      Computational tools can help in simultaneously analyzing many different pieces of
      biological knowledge from different data sources. Such tools will aid in
      comprehending the whole system (cell, organism) as a function of all of its
      components; this, in turn, will facilitate discovery of the global patterns in
      genetic regulation. The Worm Community System (WCS) which contains extensive
      knowledge from many different sources regarding model organism C. elegans,
      presents a suitable environment for development of the integrated analysis tools.
      Here we describe a working version of WCS and the strategies employed for the
      development of the global analysis tools within the System. The present paper
      deals with the construction of a highly interconnected information space (in the
      context of the problem) by introducing more sophisticated data objects
      representing knowledge about genetic regulation. We describe construction of the
      in-depth objects, development of the analysis tools and discuss the type of
      analysis feasible within such interconnected space. The analysis tools will serve
      as an ideal environment for 'dry biology' experimentation and provide a context
      for 'wet' experiments.

PMID- 7584366
TI  - Transmembrane segment prediction from protein sequence data.
AB  - We consider the automated identification of transmembrane domains in membrane
      protein sequences. 324 proteins (containing 1585 segments) were examined,
      representing every protein in the PIR database having the transmembrane domain
      feature annotation. Machine learning techniques were used to evaluate the
      efficacy of alternative hydrophobicity measures and windowing techniques. We
      describe a simpler measure of hydrophobicity and a new variable window size
      concept. We demonstrate that these techniques are superior to some previous
      techniques in minimizing the segment error rate. Using these new techniques, we
      describe an algorithm that has a 7.9% segment error rate on the sampled proteins,
      while classifying 16.7% of the amino acid residues as transmembrane.

PMID- 7584363
TI  - Hidden Markov models and iterative aligners: study of their equivalence and
      possibilities.
AB  - There are many shared attributes between existing iterative aligners and Hidden
      Markov Model (HMM). A learning algorithm of HMM called Viterbi is the same as the
      iteration of DP-matching of iterative aligners. HMM aligners can use the result
      of an iterative aligner initially, incorporate the similarity score of amino
      acids, and apply the detailed gap cost systems to improve the matching accuracy.
      On the other hand, the iterative aligner can inherit the modeling capability of
      HMM, and provide the better representation of the proteins than motifs. In this
      paper, we present an overview of several iterative aligners which include the
      parallel iterative aligner of ICOT and the HMM aligner of Haussler's group. We
      compare the merits and shortcomings of these aligners. This comparison enables us
      to formulate a better, more advanced aligner through proper integration of the
      iterative technique and HMM technique.

PMID- 7584364
TI  - Protein structure prediction system based on artificial neural networks.
AB  - Methods based on the neural network techniques are among the most accurate in the
      secondary structure prediction of globular proteins. Here the same principles
      have been used for the tertiary structure prediction problem. The map of dihedral
      phi and psi angles is divided into 10 by 10 squares each spanning 36 by 36
      degrees. By predicting the classification of each residue in the protein chain in
      this map a rough tertiary structure can be deduced. A complete prediction system
      running on a cluster of workstations and a graphical user interface was
      developed.

PMID- 7584367
TI  - Neural networks for molecular sequence classification.
AB  - A neural network classification method has been developed as an alternative
      approach to the search/organization problem of large molecular databases. Two
      artificial neural systems have been implemented on a Cray supercomputer for rapid
      protein/nucleic acid sequence classifications. The neural networks used are three
      layered, feed-forward networks that employ back-propagation learning algorithm.
      The molecular sequences are encoded into neural input vectors by applying an n
      gram hashing method or a SVD (singular value decomposition) method. Once trained
      with known sequences in the molecular databases, the neural system becomes an
      associative memory capable of classifying unknown sequences based on the class
      information embedded in its neural interconnections. The protein system, which
      classifies proteins into PIR (Protein Identification Resource) superfamilies,
      showed a 82% to a close to 100% sensitivity at a speed that is about an order of
      magnitude faster than other search methods. The pilot nucleic acid system, which
      classifies ribosomal RNA sequences according to phylogenetic groups, has achieved
      a 100% classification accuracy. The system could be used to reduce the database
      search time and help organize the molecular sequence databases. The tool is
      generally applicable to any databases that are organized according to family
      relationships.

PMID- 7584369
TI  - A constraint reasoning system for automating sequence-specific resonance
      assignments from multidimensional protein NMR spectra.
AB  - AUTOASSIGN is a prototype expert system designed to aid in the determination of
      protein structure from nuclear magnetic resonance (NMR) measurements. In this
      paper we focus on one of the key steps of this process, the assignment of the
      observed NMR signals to specific atomic nuclei in the protein; i.e. the
      determination of sequence-specific resonance assignments. Recently developed
      triple-resonance (1H, 15N, and 13C) NMR experiments [Montelione et al., 1992]
      have provided an important breakthrough in this field, as the resulting data are
      more amenable to automated analysis than data sets generated using conventional
      strategies [Wuethrich, 1986]. The "assignment problem" can be stated as a
      constraint satisfaction problem (CSP) with some added complexities. There is very
      little internal structure to the problem, making it difficult to apply subgoaling
      and problem decomposition. Moreover, the data used to generate the constraints
      are incomplete, non-unique, and noisy, and constraints emerge dynamically as
      analysis progresses. The traditional inference engine is replaced by a set of
      very tightly-coupled modules which enforce extensive constraint propagation, with
      state information distributed over the objects whose relationships are being
      constrained. AUTOASSIGN provides correct and nearly complete resonance
      assignments with both simulated and real 3D triple-resonance data for a 72 amino
      acid protein.

PMID- 7584368
TI  - Automatic derivation of substructures yields novel structural building blocks in
      globular proteins.
AB  - Because the general problem of predicting the tertiary structure of a globular
      protein from its sequence is so difficult, researchers have tried to predict
      regular substructures, known as secondary structures, of proteins. Knowledge of
      the position of these structures in the sequence can significantly constrain the
      possible conformations of the protein. Traditional protein secondary structures
      are alpha-helices, beta-sheets, and coil. Secondary structure prediction programs
      have been developed, based upon several different algorithms. Such systems,
      despite their varied natures, are noted for their universal limit on prediction
      accuracy of about 65%. A possible cause for this limit is that traditional
      secondary structure classes are only a coarse characterization of local structure
      in proteins. This work presents the results of an alternative approach where
      local structure classes in proteins are derived using neural network and
      clustering techniques. These give a set of local structure categories, which we
      call Structural Building Blocks (SBBs), based upon the data itself, rather than a
      priori categories imposed upon the data. Analysis of SBBs shows that these
      categories are general classifications, and that they account for recognized
      helical and strand regions, as well as novel categories such as N- and C-caps of
      helices and strands.

PMID- 7584370
TI  - Using Dirichlet mixture priors to derive hidden Markov models for protein
      families.
AB  - A Bayesian method for estimating the amino acid distributions in the states of a
      hidden Markov model (HMM) for a protein family or the columns of a multiple
      alignment of that family is introduced. This method uses Dirichlet mixture
      densities as priors over amino acid distributions. These mixture densities are
      determined from examination of previously constructed HMMs or multiple
      alignments. It is shown that this Bayesian method can improve the quality of HMMs
      produced from small training sets. Specific experiments on the EF-hand motif are
      reported, for which these priors are shown to produce HMMs with higher likelihood
      on unseen data, and fewer false positives and false negatives in a database
      search task.

PMID- 7584371
TI  - FLASH: a fast look-up algorithm for string homology.
AB  - A key issue in managing today's large amounts of genetic data is the availability
      of efficient, accurate, and selective techniques for detecting homologies
      (similarities) between newly discovered and already stored sequences. A common
      characteristic of today's most advanced algorithms, such as FASTA, BLAST, and
      BLAZE is the need to scan the contents of the entire database, in order to find
      one or more matches. This design decision results in either excessively long
      search times or, as is the case of BLAST, in a sharp trade-off between the
      achieved accuracy and the required amount of computation. The homology detection
      algorithm presented in this paper, on the other hand, is based on a probabilistic
      indexing framework. The algorithm requires minimal access to the database in
      order to determine matches. This minimal requirement is achieved by using the
      sequences of interest to generate a highly redundant number of very descriptive
      tuples; these tuples are subsequently used as indices in a table look-up
      paradigm. In addition to the description of the algorithm, theoretical and
      experimental results on the sensitivity and accuracy of the suggested approach
      are provided. The storage and computational requirements are described and the
      probability of correct matches and false alarms is derived. Sensitivity and
      accuracy are shown to be close to those of dynamic programming techniques. A
      prototype system has been implemented using the described ideas. It contains the
      full Swiss-Prot database rel 25 (10 MR) and the genome of E. Coli (2 MR). The
      system is currently being expanded to include the complete Genbank
      database.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584374
TI  - Protein topology prediction through parallel constraint logic programming.
AB  - In this paper, two programs are described (CBS1e and CBS2e). These are
      implemented in the parallel constraint logic programming language ElipSys. These
      predict protein alpha/beta-sheet and beta-sheet topologies from secondary
      structure assignments and topological folding rules (constraints). These programs
      illustrate how recent developments in logic programming environments can be
      applied to solve large-scale combinatorial problems in molecular biology. We
      demonstrate that parallel constraint logic programming is able to overcome some
      of the important limitations of more established logic programming languages i.e.
      Prolog. This is particularly the case in providing features that enhance the
      declarative nature of the program and also in addressing directly the problems of
      scaling-up logic programs to solve scientifically realistic problems. Moreover,
      we show that for large topological problems CBS1e was approximately 60 times
      faster than an equivalent Prolog implementation (CBS1) on a sequential device
      with further performance enhancements possible on parallel computer
      architectures. CBS2e is an extension of CBS1e that addresses the important
      problem of integrating the use of uncertain (weighted) protein folding
      constraints with categorical ones, through the use of a cost function that is
      minimized. CBS2e achieves this with a relatively minor reduction of performance.
      These results significantly extend the range and complexity of protein structure
      prediction methods that can reasonably be addressed using AI languages.

PMID- 7584373
TI  - Protein structure prediction: selecting salient features from large candidate
      pools.
AB  - We introduce a parallel approach, "DT-SELECT," for selecting features used by
      inductive learning algorithms to predict protein secondary structure. DT-SELECT
      is able to rapidly choose small, nonredundant feature sets from pools containing
      hundreds of thousands of potentially useful features. It does this by building a
      decision tree, using features from the pool, that classifies a set of training
      examples. The features included in the tree provide a compact description of the
      training data and are thus suitable for use as inputs to other inductive learning
      algorithms. Empirical experiments in the protein secondary-structure task, in
      which sets of complex features chosen by DT-SELECT are used to augment a standard
      artificial neural network representation, yield surprisingly little performance
      gain, even though features are selected from very large feature pools. We discuss
      some possible reasons for this result.

PMID- 7584372
TI  - Toward multistrategy parallel and distributed learning in sequence analysis.
AB  - Machine learning techniques have been shown to be effective in sequence analysis
      tasks. However, current learning algorithms, which are typically serial main
      memory-based, are not capable of handling the vast amounts of information being
      generated by the Human Genome Project. The multistrategy parallel learning
      approach presented in this paper is an attempt to scale existing learning
      algorithms. Learning speed is improved through running multiple learning
      processes in parallel and prediction accuracy is improved through multiple
      learners. Our approaches are independent of the learning algorithms used. This
      paper focuses on one of the MSPL approaches and preliminary empirical results
      that we present are encouraging.

PMID- 7584376
TI  - Proceedings of the 2nd International Conference on Intelligent Systems for
      Molecular Biology. ISMB--94.

PMID- 7584375
TI  - Knowledge-based generation of machine learning experiments: learning with DNA
      crystallography data.
AB  - Though it has been possible in the past to learn to predict DNA hydration
      patterns from crystallographic data, there is ambiguity in the choice of training
      data (both in terms of the relevant set of cases and the features needed to
      represent them), which limits the usefulness of standard learning techniques.
      Thus, we have developed a knowledge-based system to generate machine learning
      experiments for inducing DNA hydration pattern classifiers. The system takes as
      input (1) a set of classified training examples described by a large set of
      attributes and (2) information about a set of learning experiments that have
      already been run. It outputs a new learning experiment, namely a (not necessarily
      proper) subset of the input examples represented by a new set of features. Domain
      specific and domain independent knowledge is used to suggest subsets of training
      examples from suspected subpopulations, transform attributes in the training data
      or generate new ones, and choose interesting ways to substitute one experiment's
      set of attributes with another. Automatic hydration pattern predictors are of
      both theoretical and practical interest to DNA crystallographers, because they
      can speed up a labor intensive process, and because the extracted rules add to
      the knowledge of what determines DNA hydration.

PMID- 7584377
TI  - The Repeat Pattern Toolkit (RPT): analyzing the structure and evolution of the C.
      elegans genome.
AB  - Over 3.6 million bases of DNA sequence from chromosome III of the C. elegans have
      been determined. The availability of this extended region of contiguous sequence
      has allowed us to analyze the nature and prevalence of repetitive sequences in
      the genome of a eukaryotic organism with a high gene density. We have assembled a
      Repeat Pattern Toolkit (RPT) to analyze the patterns of repeats occurring in DNA.
      The tools include identifying significant local alignments (utilizing both two
      way and three-way alignments), dividing the set of alignments into connected
      components (signifying repeat families), computing evolutionary distance between
      repeat family members, constructing minimum spanning trees from the connected
      components, and visualizing the evolution of the repeat families. Over 7000
      families of repetitive sequences were identified. The size of the families ranged
      from isolated pairs to over 1600 segments of similar sequence. Approximately
      12.3% of the analyzed sequence participates in a repeat element.

PMID- 7584378
TI  - Constraint satisfaction techniques for modeling large complexes: application to
      the central domain of 16S ribosomal RNA.
AB  - Standard experimental techniques for determining the structure of small to
      moderately-sized molecules are difficult to apply to large macromolecular
      complexes. These complexes, consisting of multiple protein and/or nucleic acid
      components, can contain many thousands of atoms and the experimental techniques
      used to study them provide relatively sparse structural information with
      significant measurement uncertainty. Computational technologies are required to
      reduce the conformational search space and synthesize the data in order to
      produce the structures or (more usually) sets of structures compatible with the
      data. In this paper, we show that a method based on the constraint satisfaction
      paradigm produces a three-dimensional topology for the central domain of the 16S
      ribosomal RNA that is generally consistent with interactively built models,
      although differing in significant ways. The modeling incorporates information
      about secondary structure of the nucleic acid, neutron diffraction data about the
      relative positions and uncertainties of the proteins, and protection experiments
      indicating proximities of segments of RNA to specific protein subunits. Unlike
      previously proposed models, our model contains explicit information about the
      range of positions for each subunit that are compatible with the data. The system
      uses a grid search, checks distances in a direction-dependent manner, uses
      disjunctive distance constraints, and checks for volume overlap violations.

PMID- 7584379
TI  - Using interval logic for order assembly.
AB  - Temporal logic, in particular, interval logic has been used to represent genome
      maps and to assist genome map constructions. However, interval logic itself
      appears to be limited in its expressive power because genome mapping requires
      various information such as partial order, distance and local orientation. In
      this paper, we first propose an integrated formalism based on a spatial-temporal
      logic where the concepts of metric information, local orientation and uncertainty
      are merged. Then, we present and discuss a deductive and object-oriented data
      model based on this formalism for a genetic deductive database, and the inference
      rules required. The formalism supports the maintenance of coarser knowledge of
      unordered, partially ordered and completely ordered genetic data in a relational
      hierarchy. We believe that this integrated formalism also provides a formal basis
      for designing a declarative query language.

PMID- 7584380
TI  - A restriction mapping engine using constraint logic programming.
AB  - Restriction mapping generally requires the application of information from
      various digestions by restriction enzymes to find solution sets. We use both the
      predicate calculus and constraint solving capabilities of CLP(R) to develop an
      engine for restriction mapping. Many of the techniques employed by biologists to
      manually find solutions are supported by the engine in a consistent manner. We
      provide generalized pipeline and cross-multiply operators for combining sub-maps.
      Our approach encourages the building of maps iteratively. We show how other
      techniques can be readily incorporated.

PMID- 7584381
TI  - Stochastic motif extraction using hidden Markov model.
AB  - In this paper, we study the application of an HMM (hidden Markov model) to the
      problem of representing protein sequences by a stochastic motif. A stochastic
      protein motif represents the small segments of protein sequences that have a
      certain function or structure. The stochastic motif, represented by an HMM, has
      conditional probabilities to deal with the stochastic nature of the motif. This
      HMM directly reflects the characteristics of the motif, such as a protein
      periodical structure or grouping. In order to obtain the optimal HMM, we
      developed the "ilerative duplication method" for HMM topology learning. It starts
      from a small fully-connected network and iterates the network generation and
      parameter optimization until it achieves sufficient discrimination accuracy.
      Using this method, we obtained an HMM for a leucine zipper motif. Compared to the
      accuracy of a symbolic pattern representation with accuracy of 14.8 percent, an
      HMM achieved 79.3 percent in prediction. Additionally, the method can obtain an
      HMM for various types of zinc finger motifs, and it might separate the mixed
      data. We demonstrated that this approach is applicable to the validation of the
      protein database; a constructed HMM has indicated that one protein sequence
      annotated as "leucine-zipper like sequence" in the database is quite different
      from other leucine-zipper sequences in terms of likelihood, and we found this
      discrimination is plausible.

PMID- 7584382
TI  - Assigning function to CDS through qualified query answering: beyond alignment and
      motifs.
AB  - In this paper, we show how to use qualitative query answering to annotate CDS-to
      function relationships with confidence in the score, confidence in the tool, and
      confidence in the decision about the function. The system, implemented in Prolog,
      provides users with a powerful tool to analyze large quantities of data that have
      been produce by multiple sequence analysis programs. Using qualified query
      answering techniques, users can easily change the criteria for how tools
      reinforce each other and for how numbers of occurrences of particular functions
      reinforce each other. They can also alter how different scores for different
      tools are categorized.

PMID- 7584383
TI  - RNA modeling using Gibbs sampling and stochastic context free grammars.
AB  - A new method of discovering the common secondary structure of a family of
      homologous RNA sequences using Gibbs sampling and stochastic context-free
      grammars is proposed. Given an unaligned set of sequences, a Gibbs sampling step
      simultaneously estimates the secondary structure of each sequence and a set of
      statistical parameters describing the common secondary structure of the set as a
      whole. These parameters describe a statistical model of the family. After the
      Gibbs sampling has produced a crude statistical model for the family, this model
      is translated into a stochastic context-free grammar, which is then refined by an
      Expectation Maximization (EM) procedure to produce a more complete model. A
      prototype implementation of the method is tested on tRNA, pieces of 16S rRNA and
      on U5 snRNA with good results.

PMID- 7584384
TI  - Creating a knowledge base of biological research papers.
AB  - Intelligent text-oriented tools for representing and searching the biological
      research literature are being developed, which combine object-oriented databases
      with artificial intelligence techniques to create a richly structured knowledge
      based of Materials and Methods sections of biological research papers. A
      knowledge model of experimental processes, biological and chemical substances,
      and analytical techniques is described, based on the representation techniques of
      taxonomic semantic nets and knowledge frames. Two approaches to populating the
      knowledge base with the contents of biological research papers are described:
      natural language processing and an interactive knowledge definition tool.

PMID- 7584385
TI  - The prediction of the degree of exposure to solvent of amino acid residues via
      genetic programming.
AB  - In this paper I evolve programs that predict the degree of exposure to solvent
      (the buriedness) of amino acid residues given only the primary structure. I use
      genetic programming (Koza 1992; Koza 1994) to evolve programs that take as input
      the primary structure and that output the buriedness of each residue. I trained
      these programs on a set of 82 proteins from the Brookhaven Protein Data Bank
      (PDB) (Bernstein et al. 1977) and cross-validated them on a separate testing set
      of 40 proteins, also from the PDB. The best program evolved had a correlation of
      0.434 between the predicted and observed buriednesses on the testing set.

PMID- 7584386
TI  - A flexible approach to genome map assembly.
AB  - A major goal of the Human Genome Project is to construct detailed physical maps
      of the human genome. A physical map is an assignment of DNA fragments to their
      locations on the genome. Complete maps of large genomes require the integration
      of many kinds of experimental data, each with its own forms of noise and
      experimental error. To facilitate this integration, we are developing a flexible
      approach to map assembly based on logic programming and data visualization. Logic
      programming provides a convenient and mathematically rigorous way of reasoning
      about data, while data visualization provides layout algorithms for assembling
      and displaying genome maps. To demonstrate the approach, this paper describes
      numerous rules for map assembly implemented in a data-visualization system called
      Hy+. Using these rules, we have successfully assembled contigs (partial maps)
      from real and simulated mapping data-data that is noisy, imprecise and
      contradictory. The main advantage of the approach is that it allows a user to
      rapidly develop, implement and test new rules for genome map assembly, with a
      minimum of programming effort.

PMID- 7584387
TI  - Prototyping a genetics deductive database.
AB  - We are developing a laboratory notebook system known as the Genetics Deductive
      Database. Currently our prototype provides storage for biological facts and rules
      with flexible access via an interactive graphical display. We have introduced a
      formal basis for the representation and reasoning necessary to order genome map
      data and handle the uncertainty inherent in biological data. We aim to support
      laboratory activities by introducing an experiment planner into our prototype.
      The Genetics Deductive Database is built using new database technology which
      provides an object-oriented conceptual model, a declarative rule language, and a
      procedural update language. This combination of features allows the
      implementation of consistency maintenance, automated reasoning, and data
      verification.

PMID- 7584388
TI  - Induction of rules for biological macromolecule crystallization.
AB  - X-ray crystallography is the method of choice for determining the 3-D structure
      of large macromolecules at a high enough resolution. The rate limiting step in
      structure determination is the crystallization itself. It takes anywhere between
      a few weeks to several years to obtain macromolecular crystals that yield good
      diffraction patterns. The theory of forces that promote and maintain crystal
      growth is preliminary, and crystallographers systematically search a large
      parameter space of experimental settings to grow good crystals. There is a wealth
      of experimental data on crystal growth most of which is in paper laboratory
      notebooks. Some of the data has been gathered in electronic form, e.g., the
      Biological Macromolecular Crystallization Database (BMCD) which is a repository
      of successful experimental conditions for growing over 800 different
      macromolecules (Gilliland 1987). Crystallographers are in need of computational
      tools to gather and analyze past data to design new crystal growth trails. We are
      building the Crystallographer's Assistant (CA) to help crystallographers record
      and maintain experimental context in electronic form, offer suggestions on
      experimental conditions that are likely to be successful, and provide
      explanations for failed experiments. As an initial step in this project, we have
      applied RL, an inductive learning program, to the BMCD. In this paper we report
      initial experiments and findings in applying RL to the BMCD. From the point of
      view of crystallography, we have discovered possibly significant new empirical
      relationships in crystal growth. From the point of view of machine learning, our
      work suggests refinements of existing methods for incorporating detailed domain
      knowledge into inductive analysis techniques.

PMID- 7584391
TI  - Aligning genomes with inversions and swaps.
AB  - The decision about what operators to allow and how to charge for these operations
      when aligning strings that arise in a biological context is the decision about
      what model of evolution to assume. Frequently the operators used to construct an
      alignment between biological sequences are limited to deletion, insertion, or
      replacement of a character or block of characters, but there is biological
      evidence for the evolutionary operations of exchanging the positions of two
      segments in a sequence and the replacement of a segment by its reversed
      complement. In this paper we describe a family of heuristics designed to compute
      alignments of biological sequences assuming a model of evolution with swaps and
      inversions. The heuristics will necessarily be approximate since the appropriate
      way to charge for the evolutionary events (delete, insert, substitute, swap, and
      invert) is not known. The paper concludes with a pairwise comparison of 20
      Picornavirus genomes, and a detailed comparison of the hepatitis delta virus with
      the citrus exocortis viroid.

PMID- 7584389
TI  - Neural networks for determining protein specificity and multiple alignment of
      binding sites.
AB  - We use a quantitative definition of specificity to develop a neural network for
      the identification of common protein binding sites in a collection of unaligned
      DNA fragments. We demonstrate the equivalence of the method to maximizing
      Information Content of the aligned sites when simple models of the binding energy
      and the genome are employed. The network method subsumes those simple models and
      is capable of working with more complicated ones. This is demonstrated using a
      Markov model of the E. coli genome and a sampling method to approximate the
      partition function. A variation of Gibbs' sampling aids in avoiding local minima.

PMID- 7584390
TI  - Finding an average core structure: application to the globins.
AB  - We present a procedure for automatically identifying from a set of aligned
      protein structures a subset of atoms with only a small amount of structural
      variation, i.e., a core. We apply this procedure to the globin family of
      proteins. Based purely on the results of the procedure, we show that the globin
      fold can be divided into two parts. The part with greater structural variation
      consists of the residues near the heme (the F helix and parts of the G and H
      helices), and the part with lesser structural variation (the core) forms a
      structural framework similar to that of the repressor protein (A, B, and E
      helices and remainder of the G and H helices). Such a division is consistent with
      many other structural and biochemical findings. In addition, we find further
      partitions within the core that may have biological significance. Finally, using
      the structural core of the globin family as a reference point, we have compared
      structural variation to sequence variation and shown that a core definition based
      on sequence conservation does not necessarily agree with one based on structural
      similarity.

PMID- 7584393
TI  - An efficient method for multiple sequence alignment.
AB  - Multiple sequence alignment has been a useful method in the study of molecular
      evolution and sequence-structure relationships. This paper presents a new method
      for multiple sequence alignment based on simulated annealing technique. Dynamic
      programming has been widely used to find an optimal alignment. However, dynamic
      programming has several limitations to obtain optimal alignment. It requires long
      computation time and cannot apply certain types of cost functions. We describe
      detail mechanisms of simulated annealing for multiple sequence alignment problem.
      It is shown that simulated annealing can be an effective approach to overcome the
      limitations of dynamic programming in multiple sequence alignment problem.

PMID- 7584394
TI  - Inductive logic programming used to discover topological constraints in protein
      structures.
AB  - This paper describes the application of the Inductive Logic Programming (ILP)
      program GOLEM to the discovery of constraints in the packing of beta-sheets in
      alpha/beta proteins. These constraints (rules) have a role in understanding the
      protein folding problem. Constraints were learnt for four features of beta-sheet
      packing: the winding direction of two sequential strands, whether two consecutive
      strands pack parallel or anti-parallel, whether two strands pack adjacently, and
      whether a beta-strand is at an edge. Investigation of the learnt constraints
      revealed interesting patterns, some of which were previously known, others that
      were novel. Novel features include the discovery: that the relationship between
      pairs of sequential strands is in general one of decreasing size, and that more
      sequential pairs of strands wind in the direction out than the direction in. We
      conclude that machine learning has a useful place in molecular biology as a
      pattern discovery tool.

PMID- 7584392
TI  - Representations of metabolic knowledge: pathways.
AB  - The automatic generation of drawings of metabolic pathways is a challenging
      problem that depends intimately on exactly what information has been recorded for
      each pathway, and on how that information is encoded. The chief contributions of
      the paper are a minimized representation for biochemical pathways called the
      predecessor list, and inference procedures for converting the predecessor list
      into a pathway-graph representation that can serve as input to a pathway-drawing
      algorithm. The predecessor list has several advantages over the pathway graph,
      including its compactness and its lack of redundancy. The conversion between the
      two representations can be formulated as both a constraint-satisfaction problem
      and a logical inference problem, whose goal is to assign directions to reactions,
      and to determine which are the main chemical compounds in the reaction. We
      describe a set of production rules that solves this inference problem. We also
      present heuristics for inferring whether the exterior compounds that are
      substrates of reactions at the periphery of a pathway are side or main compounds.
      These techniques were evaluated on 18 metabolic pathways from the EcoCyc
      knowledge base.

PMID- 7584395
TI  - Toward unification of taxonomy databases in a distributed computer environment.
AB  - All the taxonomy databases constructed with the DNA databases of the
      international DNA data banks are powerful electronic dictionaries which aid in
      biological research by computer. The taxonomy databases are, however not
      consistently unified with a relational format. If we can achieve consistent
      unification of the taxonomy databases, it will be useful in comparing many
      research results, and investigating future research directions from existent
      research results. In particular, it will be useful in comparing relationships
      between phylogenetic trees inferred from molecular data and those constructed
      from morphological data. The goal of the present study is to unify the existent
      taxonomy databases and eliminate inconsistencies (errors) that are present in
      them. Inconsistencies occur particularly in the restructuring of the existent
      taxonomy databases, since classification rules for constructing the taxonomy have
      rapidly changed with biological advancements. A repair system is needed to remove
      inconsistencies in each data bank and mismatches among data banks. This paper
      describes a new methodology for removing both inconsistencies and mismatches from
      the databases on a distributed computer environment. The methodology is
      implemented in a relational database management system, SYBASE.

PMID- 7584396
TI  - Discovering side-chain correlation in alpha-helices.
AB  - Using a new representation for interactions in protein sequences based on
      correlations between pairs of amino acids, we have examined alpha-helical
      segments from known protein structures for important interactions. Traditional
      techniques for representing protein sequences usually make an explicit assumption
      of conditional independence of residues in the sequences. Protein structure
      analyses, however, have repeatedly demonstrated the importance of amino acid
      interactions for structural stability. We have developed an automated program for
      discovering sequence correlations in sets of aligned protein sequences using
      standard statistical tests and for representing them with Bayesian networks. In
      this paper, we demonstrate the power of our discovery program and representation
      by analyzing pairs of residues from alpha-helices. The sequence correlations we
      find represent physical and chemical interactions among amino-acid side chains in
      helical structures. Furthermore, these local interactions are likely to be
      important for stabilizing and packing alpha-helices. Lastly, we have also detect
      correlations in side-chain comformations that indicate important structural
      interactions but which don't appear as sequence correlations.

PMID- 7584397
TI  - Evolution of a computer program for classifying protein segments as transmembrane
      domains using genetic programming.
AB  - The recently-developed genetic programming paradigm is used to evolve a computer
      program to classify a given protein segment as being a transmembrane domain or
      non-transmembrane area of the protein. Genetic programming starts with a
      primordial ooze of randomly generated computer programs composed of available
      programmatic ingredients and then genetically breeds the population of programs
      using the Darwinian principle of survival of the fittest and an analog of the
      naturally occurring genetic operation of crossover (sexual recombination).
      Automatic function definition enables genetic programming to dynamically create
      subroutines dynamically during the run. Genetic programming is given a training
      set of differently-sized protein segments and their correct classification (but
      no biochemical knowledge, such as hydrophobicity values). Correlation is used as
      the fitness measure to drive the evolutionary process. The best genetically
      evolved program achieves an out-of-sample correlation of 0.968 and an out-of
      sample error rate of 1.6%. This error rate is better than that reported for four
      other algorithms reported at the First International Conference on Intelligent
      Systems for Molecular Biology. Our genetically evolved program is an instance of
      an algorithm discovered by an automated learning paradigm that is superior to
      that written by human investigators.

PMID- 7584398
TI  - DNA sequence analysis using hierarchical ART-based Classification Networks.
AB  - Adaptive resonance theory (ART) describes a class of artificial neural network
      architectures that act as classification tools which self-organize, work in
      realtime, and require no retraining to classify novel sequences. We have adapted
      ART networks to provide support to scientists attempting to categorize tandem
      repeat DNA fragments from Onchocerca volvulus. In this approach, sequences of DNA
      fragments are presented to multiple ART-based networks which are linked together
      into two (or more) tiers; the first provides coarse sequence classification while
      the subsequent tiers refine the classifications as needed. The overall rating of
      the resulting classification of fragments is measured using statistical
      techniques based on those introduced by Zimmerman, et al. (1994) to validate
      results from traditional phylogenetic analysis. Tests of the Hierarchical ART
      based Classification Network, or HABclass network, indicate its value as a fast,
      easy-to-use classification tool which adapts to new data without retraining on
      previously classified data.

PMID- 7584399
TI  - Segmentation and interpretation of 3D protein images.
AB  - The segmentation and interpretation of three-dimensional images of proteins is
      considered. A topological approach is used to represent a protein structure as a
      spanning tree of critical points, where each critical point corresponds to a
      residue or the connectivity between residues. The critical points are
      subsequently analyzed to recognize secondary structure motifs within the protein.
      Results of applying the approach to ideal and experimental images of proteins at
      medium resolution are presented.

PMID- 7584400
TI  - High speed pattern matching in genetic data base with reconfigurable hardware.
AB  - Homology detection in large data bases is probably the most time consuming
      operation in molecular genetic computing systems. Moreover, the progresses made
      all around the world concerning the mapping and sequencing of the genome of Homo
      Sapiens and other species have increased the size of data bases exponentially.
      Therefore even the best workstation would not be able to reach the scanning speed
      required. In order to answer this need we propose an algorithm, A2R2, and its
      implementation on a massively parallel system. Basically, two kinds of algorithms
      are used to search in molecular genetic data bases. The first kind is based on
      dynamic programming and the second on word processing, A2R2 belongs to the second
      kind. The structure of the motif (pattern) searched by A2R2 can support those
      from FAST, BLAST and FLASH algorithms. After a short presentation of the
      reconfigurable hardware concept and technology used in our massively parallel
      accelerator we present the A2R2 implementation. This parallel implementation
      outperforms any kind of previously published genetic data base scanning hardware
      or algorithms. We report up to 25 million nucleotides per scanning seconds as our
      best results.

PMID- 7584402
TI  - Fitting a mixture model by expectation maximization to discover motifs in
      biopolymers.
AB  - The algorithm described in this paper discovers one or more motifs in a
      collection of DNA or protein sequences by using the technique of expectation
      maximization to fit a two-component finite mixture model to the set of sequences.
      Multiple motifs are found by fitting a mixture model to the data,
      probabilistically erasing the occurrences of the motif thus found, and repeating
      the process to find successive motifs. The algorithm requires only a set of
      unaligned sequences and a number specifying the width of the motifs as input. It
      returns a model of each motif and a threshold which together can be used as a
      Bayes-optimal classifier for searching for occurrences of the motif in other
      databases. The algorithm estimates how many times each motif occurs in each
      sequence in the dataset and outputs an alignment of the occurrences of the motif.
      The algorithm is capable of discovering several different motifs with differing
      numbers of occurrences in a single dataset.

PMID- 7584401
TI  - Predicting location and structure of beta-sheet regions using stochastic tree
      grammars.
AB  - We describe and demonstrate the effectiveness of a method of predicting protein
      secondary structures, beta-sheet regions in particular, using a class of
      stochastic tree grammars as representational language for their amino acid
      sequence patterns. The family of stochastic tree grammars we use, the Stochastic
      Ranked Node Rewriting Grammars (SRNRG), is one of the rare families of stochastic
      grammars that are expressive enough to capture the kind of long-distance
      dependencies exhibited by the sequences of beta-sheet regions, and at the same
      time enjoy relatively efficient processing. We applied our method on real data
      obtained from the HSSP database and the results obtained are encouraging: Using
      an SRNRG trained by data of a particular protein, our method was actually able to
      predict the location and structure of beta-sheet regions in a number of different
      proteins, whose sequences are less than 25 per cent homologous to the training
      sequences. The learning algorithm we use is an extension of the 'Inside-Outside'
      algorithm for stochastic context free grammars, but with a number of significant
      modifications. First, we restricted the grammars used to be members of the
      'linear' subclass of SRNRG, and devised simpler and faster algorithms for this
      subclass. Secondly, we reduced the alphabet size (i.e. the number of amino acids)
      by clustering them using their physicochemical properties, gradually through the
      iterations of the learning algorithm. Finally, we parallelized our parsing
      algorithm to run on a highly parallel computer, a 32-processor CM-5, and were
      able to obtain a nearly linear speed-up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584403
TI  - Kinematic manipulation of molecular chains subject to rigid constraints.
AB  - We present algorithms for kinematic manipulation of molecular chains subject to
      fixed bond lengths and bond angles. They are useful for calculating conformations
      of a molecule subject to geometric constraints, such as those derived from two
      dimensional NMR experiments. Other applications include searching out the full
      range of conformations available to a molecule such as cyclic configurations. We
      make use of results from robot kinematics and recently developed algorithms for
      solving polynomial systems. In particular, we model the molecule as a serial
      chain using the Denavit-Hartenberg formulation and reduce these problems to
      inverse kinematics of a serial chain. We also highlight the relationship between
      molecular embedding problems and inverse kinematics. As compared to earlier
      methods, the main advantages of the kinematic formulation are its generality to
      all molecular chains without any restrictions on the geometry and efficiency in
      terms of performance. The algorithms give us real time performance (order of tens
      of milliseconds) on smaller chains and are applicable to all chains.

PMID- 7584405
TI  - Sequence comparisons via algorithmic mutual information.
AB  - One of the main problems in DNA and protein sequence comparisons is to decide
      whether observed similarity of two sequences should be explained by their
      relatedness or by mere presence of some shared internal structure, e.g., shared
      internal tandem repeats. The standard methods that are based on statistics or
      classical information theory can be used to discover either internal structure or
      mutual sequence similarity, but cannot take into account both. Consequently,
      currently used methods for sequence comparison employ "masking" techniques that
      simply eliminate sequences that exhibit internal repetitive structure prior to
      sequence comparisons. The "masking" approach precludes discovery of homologous
      sequences of moderate or low complexity, which abound at both DNA and protein
      levels. As a solution to this problem, we propose a general method that is based
      on algorithmic information theory and minimal length encoding. We show that
      algorithmic mutual information factors out the sequence similarity that is due to
      shared internal structure and thus enables discovery of truly related sequences.
      We extend that recently developed algorithmic significance method (Milosavljevic
      & Jurka 1993) to show that significance depends exponentially on algorithmic
      mutual information.

PMID- 7584406
TI  - Flow cytometry data analysis: comparing large multivariate data sets using
      classification trees.
AB  - This paper describes a method to compare flow cytometry data sets, which
      typically contain 50,000 six-parameter measurements each. By this method, the
      data points in two such data sets are divided into subpopulations using a binary
      classification tree generated from the data. The chi 2 test is then used to
      establish the homogeneity of the two data sets based on how their data are
      distributed across these subpopulations. Preliminary results indicate that this
      comparison method is sufficiently sensitive to detect differences between flow
      cytometry data sets that are too subtle for human investigators to notice.

PMID- 7584407
TI  - The Multi-Scale 3D-1D compatibility scoring for inverse protein folding problem.
AB  - The applicability of the Multi-Scale Structure Description (MSSD) scheme to the
      inverse-folding problems was investigated. An MSSD represents a 3D protein
      structure with multiple symbolic sequences, where fine structures are represented
      with the sequence at low levels, the middle scale structural motifs at middle
      levels, and global topology at high levels. Each symbol in the symbolic sequence
      denotes a type of local structure of the level scale. The structure fragments are
      classified at each scale level respectively according to the shape and the
      environment around the fragments: how the structure is exposed to the solvent or
      buried in the molecule. I modeled the propensity of an amino-acid sequence to the
      structure fragment type (i.e., primary constraint) at each scale level. The local
      propensity is, therefore, modeled at small scale (low) levels, while the global
      propensity modeled at large scale (high) levels. Thus, superposing all the
      primary constraint, a 3D protein structure yields an amino-acid sequence profile.
      Evaluating the fit of an amino acid sequence to the profile derived from the
      known 3D protein structure, we can identify which 3D structure the given amino
      acid sequence would fold into. I checked whether a sequence identifies its own
      structure over two hundred protein sequences. In many cases, an amino acid
      sequence identified its own 3D protein structure.

PMID- 7584408
TI  - Geometric problems in molecular biology and robotics.
AB  - Some of the geometric problems of interest to molecular biologists have
      macroscopic analogues in the field of robotics. Two examples of such analogies
      are those between protein docking and model-based perception, and between ring
      closure and inverse kinematics. Molecular dynamics simulation, too, has much in
      common with the study of robot dynamics. In this paper we give a brief survey of
      recent work on these and related problems.

PMID- 7584404
TI  - Describing multiple levels of abstraction in the metabolism.
AB  - We discuss some central issues that arise in the computer representation of the
      metabolism and its subsystems. We provide a framework for the representation of
      metabolites and bioreactions at multiple levels of detail. The framework is based
      on defining an explicit linear mapping of metabolites and reactions from one
      level of detail to another. A simple reaction mechanism serves as an illustration
      and shows the emergence of the concept of a catalyst from metabolic abstraction
      levels.

PMID- 7584409
TI  - Intelligent DNA-based molecular diagnostics using linked genetic markers.
AB  - This paper describes a knowledge-based system for molecular diagnostics, and its
      application to fully automated diagnosis of X-linked genetic disorders. Molecular
      diagnostic information is used in clinical practice for determining genetic
      risks, such as carrier determination and prenatal diagnosis. Initially, blood
      samples are obtained from related individuals, and PCR amplification is
      performed. Linkage-based molecular diagnosis then entails three data analysis
      steps. First, for every individual, the alleles (i.e., DNA composition) are
      determined at specified chromosomal locations. Second, the flow of genetic
      material among the individuals is established. Third, the probability that a
      given individual is either a carrier of the disease or affected by the disease is
      determined. The current practice is to perform each of these three steps
      manually, which is costly, time consuming, labor-intensive, and error-prone. As
      such, the knowledge-intensive data analysis and interpretation supersede the
      actual experimentation effort as the major bottleneck in molecular diagnostics.
      By examining the human problem solving for the task, we have designed and
      implemented a prototype knowledge-based system capable of fully automating
      linkage-based molecular diagnostics in X-linked genetic disorders, including
      Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation
      of gel electrophoresis images to determine individual DNA marker labels, a
      constraint satisfaction search for consistent genetic flow among individuals, and
      a blackboard-style problem solver for risk assessment. We describe the system's
      successful diagnosis of DMD carrier and affected individuals from raw clinical
      data.

PMID- 7584410
TI  - Distributed machine learning: scaling up with coarse-grained parallelism.
AB  - Machine learning methods are becoming accepted as additions to the biologists
      data-analysis tool kit. However, scaling these techniques up to large data sets,
      such as those in biological and medical domains, is problematic in terms of both
      the required computational search effort and required memory (and the detrimental
      effects of excessive swapping). Our approach to tackling the problem of scaling
      up to large datasets is to take advantage of the ubiquitous workstation networks
      that are generally available in scientific and engineering environments. This
      paper introduces the notion of the invariant-partitioning property--that for
      certain evaluation criteria it is possible to partition a data set across
      multiple processors such that any rule that is satisfactory over the entire data
      set will also be satisfactory on at least one subset. In addition, by taking
      advantage of cooperation through interprocess communication, it is possible to
      build distributed learning algorithms such that only rules that are satisfactory
      over the entire data set will be learned. We describe a distributed learning
      system, CorPRL, that takes advantage of the invariant-partitioning property to
      learn from very large data sets, and present results demonstrating CorPRL's
      effectiveness in analyzing data from two databases.

PMID- 7584411
TI  - GeneQuiz: a workbench for sequence analysis.
AB  - We present the prototype of a software system, called GeneQuiz, for large-scale
      biological sequence analysis. The system was designed to meet the needs that
      arise in computational sequence analysis and our past experience with the
      analysis of 171 protein sequences of yeast chromosome III. We explain the
      cognitive challenges associated with this particular research activity and
      present our model of the sequence analysis process. The prototype system consists
      of two parts: (i) the database update and search system (driven by perl programs
      and rdb, a simple relational database engine also written in perl) and (ii) the
      visualization and browsing system (developed under C++/ET++). The principal
      design requirement for the first part was the complete automation of all
      repetitive actions: database updates, efficient sequence similarity searches and
      sampling of results in a uniform fashion. The user is then presented with "hit
      lists" that summarize the results from heterogeneous database searches. The
      expert's primary task now simply becomes the further analysis of the candidate
      entries, where the problem is to extract adequate information about functional
      characteristics of the query protein rapidly. This second task is tremendously
      accelerated by a simple combination of the heterogeneous output into uniform
      relational tables and the provision of browsing mechanisms that give access to
      database records, sequence entries and alignment views. Indexing of molecular
      sequence databases provides fast retrieval of individual entries with the use of
      unique identifiers as well as browsing through databases using pre-existing cross
      references. The presentation here covers an overview of the architecture of the
      system prototype and our experiences on its applicability in sequence
      analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584412
TI  - The prediction of human exons by oligonucleotide composition and discriminant
      analysis of spliceable open reading frames.
AB  - Discriminant analysis is applied to the problem of recognition 5'-, internal and
      3'-exons in human DNA sequences. Specific recognition functions were developed
      for revealing exons of particular types. The method based on a splice site
      prediction algorithm that uses the linear Fisher discriminant to combine the
      information about significant triplet frequencies of various functional parts of
      splice site regions and preferences of oligonucleotides in protein coding and
      intron regions (Solovyev, Lawrence, 1994). The accuracy of our splice site
      recognition function is about 97%. A discriminant function for 5'-exon prediction
      includes hexanucleotide composition of upstream region, triplet composition
      around the ATG codon, ORF coding potential, donor splice site potential and
      composition of downstream intron region. For internal 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% and a level of pseudoexon ORF
      prediction of 99.96%. The recognition quality computed at the level of individual
      nucleotides is 89% for exon sequences and 98% for intron sequences. A
      discriminant function for 3'-exon prediction includes octanucleotide composition
      of upstream intron region, triplet composition around the stop codon, ORF coding
      potential, acceptor splice site potential and hexanucleotide composition of
      downstream region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584413
TI  - An expert system for processing sequence homology data.
AB  - When confronted with the task of finding homology to large numbers of sequences,
      database searching tools such as Blast and Fasta generate prohibitively large
      amounts of information. An automatic way of making most of the decisions a
      trained sequence analyst would make was developed by means of a rule-based expert
      system combined with an algorithm to avoid non-informative biased residue
      composition matches. The results found relevant by the system are presented in a
      very concise and clear way, so that the homology can be assessed with minimum
      effort. The expert system, HSPcrunch, was implemented to process the output to
      the programs in the BLAST suite. HSPcrunch embodies rules on detecting distant
      similarities when pairs of weak matches are consistent with a larger gapped
      alignment, i.e. when Blast has broken a longer gapped alignment up into smaller
      ungapped ones. This way, more distant similarities can be detected with no or
      little side-effects of more spurious matches. The rules for how small the gaps
      must be to be considered significant have been derived empirically. Currently a
      set of rules are used that operate on two different scoring levels, one for very
      weak matches that have very small gaps and one for medium weak matches that have
      slightly larger gaps. This set of rules proved to be robust for most cases and
      gives high fidelity separation between real homologies and spurious matches. One
      of the most important rules for reducing the amount of output is to limit the
      number of overlapping matches to the same region of the query sequence.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584414
TI  - Optimally parsing a sequence into different classes based on multiple types of
      evidence.
AB  - We consider the problem of parsing a sequence into different classes of
      subsequences. Two common examples are finding the exons and introns in genomic
      sequences and identifying the secondary structure domains of protein sequences.
      In each case there are various types of evidence that are relevant to the
      classification, but none are completely reliable, so we expect some weighted
      average of all the evidence to provide improved classifications. For example, in
      the problem of identifying coding regions in genomic DNA, the combined use of
      evidence such as codon bias and splice junction patterns can give more reliable
      predictions than either type of evidence alone. We show three main results: 1.
      For a given weighting of the evidence a dynamic programming algorithm returns the
      optimal parse and any number of sub-optimal parses. 2. For a given weighting of
      the evidence a dynamic programming algorithm determines the probability of the
      optimal parse and any number of sub-optimal parses under a natural Boltzmann
      Gibbs distribution over the set of possible parses. 3. Given a set of sequences
      with known correct parses, a dynamic programming algorithm allows one to apply
      gradient descent to obtain the weights that maximize the probability of the
      correct parses of these sequences.

PMID- 7584415
TI  - An intelligent system for comparing protein structures.
AB  - An approach to protein structure comparison is presented which uses techniques of
      artificial intelligence (AI) to generate a mapping between two protein
      structures. The approach proceeds by first identifying the seed of a possible
      mapping, and then searching for ways to extend the seed by incorporating
      corresponding elements from the two proteins. Correspondence is judged using
      heuristic functions which assess the similarity of the structural environments of
      the elements. The search can be guided by separately encoded knowledge. A
      prototype has been implemented which is able to rapidly create mappings with a
      high degree of accuracy in test cases.

PMID- 7584416
TI  - An improved system for exon recognition and gene modeling in human DNA sequences.
AB  - A new version of the GRAIL system (Uberbacher and Mural, 1991; Mural et al.,
      1992; Uberbacher et al., 1993), called GRAIL II, has recently been developed (Xu
      et al., 1994). GRAIL II is a hybrid AI system that supports a number of DNA
      sequence analysis tools including protein-coding region recognition, PolyA site
      and transcription promoter recognition, gene model construction, translation to
      protein, and DNA/protein database searching capabilities. This paper presents the
      core of GRAIL II, the coding exon recognition and gene model construction
      algorithms. The exon recognition algorithm recognizes coding exons by combining
      coding feature analysis and edge signal (acceptor/donor/translation-start sites)
      detection. Unlike the original GRAIL system (Uberbacher and Mural, 1991; Mural et
      al., 1992), this algorithm uses variable-length windows tailored to each
      potential exon candidate, making its performance almost exon length-independent.
      In this algorithm, the recognition process is divided into four steps. Initially
      a large number of possible coding exon candidates are generated. Then a rule
      based prescreening algorithm eliminates the majority of the improbable
      candidates. As the kernel of the recognition algorithm, three neural networks are
      trained to evaluate the remaining candidates. The outputs of the neural networks
      are then divided into clusters of candidates, corresponding to presumed exons.
      The algorithm makes its final prediction by picking the best canadidate from each
      cluster. The gene construction algorithm (Xu, Mural and Uberbacher, 1994) uses a
      dynamic programming approach to build gene models by using as input the clusters
      predicted by the exon recognition algorithm. Extensive testing has been done on
      these two algorithms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584417
TI  - Protein design by optimization of a sequence-structure quality function.
AB  - An automated procedure for protein design by optimization of a sequence-structure
      quality has been developed. The method selects a statistically optimal sequence
      for a particular structure, on the assumption that such a protein will adopt the
      desired structure. We present two optimization algorithms: one provides an exact
      optimization while the other uses a combinatorial technique for comparatively
      rapid results. Both are suitable for massively parallel computers. A prototype
      system was used to design sequences which should adopt the four-helix bundle
      conformation of myohemerythrin. These appear satisfactory to secondary structure
      and profile analysis. Detailed inspection reveals that the sequences are
      generally plausible but, as expected, lack some specific structural features. The
      design parameters provide some insight into the general determinants of protein
      structure.

PMID- 7584418
TI  - A generalized profile syntax for biomolecular sequence motifs and its function in
      automatic sequence interpretation.
AB  - A general syntax for expressing biomolecular sequence motifs is described, which
      will be used in future releases of the PROSITE data bank and in a similar
      collection of nucleic acid sequence motifs currently under development. The
      central part of the syntax is a regular structure which can be viewed as a
      generalization of the profiles introduced by Gribskov and coworkers. Accessory
      features implement specific motif search strategies and provide information
      helpful for the interpretation of predicted matches. Two contrasting examples,
      representing E. coli promoters and SH3 domains respectively, are shown to
      demonstrate the versatility of the syntax, and its compatibility with diverse
      motif search methods. It is argued, that a comprehensive machine-readable motif
      collection based on the new syntax, in conjunction with a standard search
      program, can serve as a general-purpose sequence interpretation and function
      prediction tool.

PMID- 7584419
TI  - Integration of competing ancillary assertions in genome assembly.
AB  - Assembly of genomic sequences and maps relies on a primary set of experimental
      data (e.g., the sequences of individual DNA fragments, or hybridization
      fingerprints of individual clone inserts), but almost always also relies on
      several streams of related but distinct kinds of data for completeness and
      accuracy of the final construction. These secondary data sets, which we term
      ancillary information, usually contain errors (as do the primary data sets,
      therefore creating the possibility of conflict between data sets), often arise
      from different experimental protocols and correspond to different scales of
      measurement, and occasionally include non-quantitative statements about the data.
      We present an approach for integration of ancillary assertions in the
      optimization of genome assembly, based on simultaneous balancing among the
      primary and secondary data sets, and include specific examples in the context of
      assembling DNA sequencing fragments to reconstruct a parent sequence.

PMID- 7584420
TI  - Design and application of a C++ macromolecular class library.
AB  - PDBlib is an extensible object oriented class library written in C++ for
      representing the 3-dimensional structure of biological macromolecules. PDBlib
      forms the kernel of a larger software framework being developed for assiting in
      knowledge discovery from macromolecular structure data. The software design
      strategy used by PDBlib, how the library may be used and several prototype
      applications that use the library are summarized. PDBlib represents the
      structural features of proteins, DNA, RNA, and complexes thereof, at a level of
      detail on a par with that which can be parsed from a Protein Data Bank (PDB)
      entry. However, the memory resident representation of the macromolecule is
      independent of the PDB entry and can be obtained from other back-end data
      sources, for example, existing relational databases and our own object oriented
      database (OOPDB) built on top of the commercial object oriented database,
      ObjectStore. At the front-end are several prototype applications that use the
      library: Macromolecular Query Language (MMQL) is based on a separate class
      library (MMQLlib) for building complex queries pertaining to macromolecular
      structure; PDBtool is an interactive structure verification tool; and PDBview, is
      a structure rendering tool used either as a standalone tool or as part of another
      application. Each of these software components are described. All software is
      available via anonymous ftp from cuhhca.hhmi.columbia.edu.

PMID- 7584421
TI  - Genetic map construction with constraints.
AB  - A pilot program, CME, is described for generating a physical genetic map from
      hybridization fingerprinting data. CME is implemented in the parallel constraint
      logic programming language ElipSys. The features of constraint logic programming
      are used to enable the integration of pre-existing mapping information (partial
      probe orders from cytogenetic maps and local physical maps) into the global map
      generation process, while parallelism enables the search space to be traversed
      more efficiently. CME was tested using data from chromosome 2 of
      Schizosaccharomyces pombe and was found able to generate maps as well as (and
      sometimes better than) a more traditional method. This paper illustrates the
      practical benefits of using a symbolic logic programming language and shows that
      the features of constraint handling and parallel execution bring the development
      of practical systems based on AI programming technologies nearer to being a
      reality.

PMID- 7584423
TI  - Knowledge discovery of multilevel protein motifs.
AB  - A new category of protein motif is introduced. This type of motif captures, in
      addition to global structure, the nested structure of its component parts. A
      dataset of four proteins is represented using this scheme. A structured machine
      discovery procedure is used to discover recurrent amino acid motifs and this
      knowledge is utilized for the expression of subsequent protein motif discoveries.
      Examples of discovered multilevel motifs are presented.

PMID- 7584422
TI  - VQLM: a Visual Query Language for Macromolecular structural databases.
AB  - Databases of macromolecular structures allow researchers to identify general
      principles of molecular behavior. They do this by providing a variety of data
      obtained under a number of different experimental conditions. Many new tools have
      been developed recently to aid in exploratory analysis of structural data.
      However, some queries of interest still require considerable manual filtering of
      data. In particular, studies attempting to make generalizations about complex
      arrangements of atoms or building blocks in macromolecular structures cannot be
      approached directly with existing tools. Such studies are frequently carried out
      on only a few structures or else require a labor-intensive process. To address
      this problem, we have developed a visual language, VQLM (Visual Query Language
      for Macromolecules). A query is formulated in this language by drawing an
      abstract picture of substructures to be searched for in the database and
      specifying constraints on the objects in them. To illustrate the usefulness of
      our language, we show how to encode a number of queries that were found
      scientifically interesting in the published literature in molecular biology. VQLM
      relies on VQL, a new database language, as its underlying engine for database
      retrieval and computation. We believe that VQLM will make macromolecular
      structural data more accessible to scientists, enabling faster and deeper data
      analysis.

PMID- 7584424
TI  - Proceedings of the 3rd International Conference on Intelligent Systems for
      Molecular Biology. ISMB--95.

PMID- 7584425
TI  - A divide and conquer approach to multiple alignment.
AB  - We present a report on work in progress on a divide and conquer approach to
      multiple alignment. The algorithm makes use of the costs calculated from applying
      the standard dynamic programming scheme to all pairs of sequences. The resulting
      cost matrices for pairwise alignment give rise to secondary matrices containing
      the additional costs imposed by fixing the path through the dynamic programming
      graph at a particular vertex. Such a constraint corresponds to a division of the
      problem obtained by slicing both sequences between two particular positions, and
      aligning the two sequences on the left and the two sequences on the right,
      charging for gaps introduced at the slicing point. To obtain an estimate for the
      additional cost imposed by forcing the multiple alignment through a particular
      vertex in the whole hypercube, we will take a (weighted) sum of secondary costs
      over all pairwise projections of the division of the problem, as defined by this
      vertex, that is, by slicing all sequences at the points suggested by the vertex.
      We then use that partition of every single sequence under consideration into two
      'halfs' which imposes a minimal (weighted) sum of pairwise additional costs,
      making sure that one of the sequences is divided somewhere close to its midpoint.
      Hence, each iteration can cut the problem size in half. As the enumeration of all
      possible partitions may restrict this approach to small-size problems, we
      eliminate futile partitions, and organize their enumeration in a way that starts
      with the most promising ones.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584426
TI  - Multiple alignment using hidden Markov models.
AB  - A simulated annealing method is described for training hidden Markov models and
      producing multiple sequence alignments from initially unaligned protein or DNA
      sequences. Simulated annealing in turn uses a dynamic programming algorithm for
      correctly sampling suboptimal multiple alignments according to their probability
      and a Boltzmann temperature factor. The quality of simulated annealing alignments
      is evaluated on structural alignments of ten different protein families, and
      compared to the performance of other HMM training methods and the ClustalW
      program. Simulated annealing is better able to find near-global optima in the
      multiple alignment probability landscape than the other tested HMM training
      methods. Neither ClustalW nor simulated annealing produce consistently better
      alignments compared to each other. Examination of the specific cases in which
      ClustalW outperforms simulated annealing, and vice versa, provides insight into
      the strengths and weaknesses of current hidden Markov model approaches.

PMID- 7584427
TI  - Characterizing oriented protein structural sites using biochemical properties.
AB  - A protein site is a region of a three-dimensional protein structure with a
      distinguishing functional or structural role. Certain sites recur in different
      protein structures (for example catalytic sites, calcium binding sites, and some
      types of turns), but maintain critical shared features. To facilitate the
      analysis of such protein sites, we have developed a computer system for analyzing
      the spatial distributions of biochemical properties around a site. The system
      takes a set of similar sites and a set of control nonsites, and finds differences
      between them. Specifically, it compares distributions of the properties
      surrounding the sites with those surrounding the nonsites, and reports
      statistically significant differences. In this paper, we use our method to
      analyze the features in the active site of the serine protease enzymes. We
      compare the use of radial distributions (shells) with 3-D grids (blocks) in the
      analysis of the active site. We demonstrate three different strategies for
      focusing attention on significant findings, based on properties of interest,
      spatial volumes of interest, and on the level of statistical significance.
      Finally, we show that the program automatically identifies conserved sequential,
      secondary structural and biophysical features of the serine protease active site,
      using noncatalytic histidine residues as a control environment.

PMID- 7584431
TI  - Parallel sequence alignment in limited space.
AB  - Sequence comparison with affine gap costs is a problem that is readily
      parallelizable on simple single-instruction, multiple-data stream (SIMD) parallel
      processors using only constant space per processing element. Unfortunately, the
      twin problem of sequence alignment, finding the optimal character-by-character
      correspondence between two sequences, is more complicated. While the innovative
      O(n2)-time and O(n)-space serial algorithm has been parallelized for multiple
      instruction, multiple-data stream (MIMD) computers with only a communication-time
      slowdown, typically O(log n), it is not suitable for hardware-efficient SIMD
      parallel processors with only local communication. This paper proposes several
      methods of computing sequence alignments with limited memory per processing
      element. The algorithms are also well-suited to serial implementation. The
      simpler algorithms feature, for an arbitrary integer L, a factor of L slowdown in
      exchange for reducing space requirements from O(n) to O(L square root of n) per
      processing element. Using this result, we describe an O(n log n) parallel time
      algorithm that requires O(log n) space per processing element on O(n) SIMD
      processing elements with only a mesh or linear interconnection network.

PMID- 7584430
TI  - Automatic RNA secondary structure determination with stochastic context-free
      grammars.
AB  - We have developed a method for predicting the common secondary structure of large
      RNA multiple alignments using only the information in the alignment. It uses a
      series of progressively more sensitive searches of the data in an iterative
      manner to discover regions of base pairing; the first pass examines the entire
      multiple alignment. The searching uses two methods to find base pairings. Mutual
      information is used to measure covariation between pairs of columns in the
      multiple alignment and a minimum length encoding method is used to detect column
      pairs with high potential to base pair. Dynamic programming is used to recover
      the optimal tree made up of the best potential base pairs and to create a
      stochastic context-free grammar. The information in the tree guides the next
      iteration of searching. The method is similar to the traditional comparative
      sequence analysis technique. The method correctly identifies most of the common
      secondary structure in 16S and 23S rRNA.

PMID- 7584428
TI  - Symbolic generation and clustering of RNA 3-D motifs.
AB  - Non canonical G.A. base pairs play important structural and functional roles in
      ribonucleic [sequence: see text] acids (RNA). In particular, the 3'-A-G-5' motif
      and three of its sequence variants have a relatively high occurrence in 16S and
      23S ribosomal RNA. Extensive 3-D modeling of these variants has allowed to
      support a previously proposed 3-D model and to identify another series of
      conformations consistent with phylogenetic data. The library of 3-D conformations
      generated by the MC-SYM program was then used to produce 3-D conformations of the
      small ribonucleotide r(GGCGAGCC)2. This new library includes the conformation
      determined by nuclear magnetic resonance spectroscopy.

PMID- 7584429
TI  - Reconstruction of metabolic networks using incomplete information.
AB  - This paper describes an approach that uses methods for automated sequence
      analysis (Gaasterland et al. August 1994) and multiple databases accessed through
      an object+attribute view of the data (Baehr et al. 1992), together with metabolic
      pathways, reaction equations, and compounds parsed into a logical representation
      from the Enzyme and Metabolic Pathway Database (Selkov, Yunus, & et.al. 1994), as
      the sources of data for automatically reconstructing a weighted partial metabolic
      network for a prokaryotic organism. Additional information can be provided
      interactively by the expert user to guide reconstruction.

PMID- 7584433
TI  - Classifying nucleic acid sub-sequences as introns or exons using genetic
      programming.
AB  - An evolutionary computation technique, genetic programming, created programs that
      classify messenger RNA sequences into one of two classes: (1) the sequence is
      expressed as (part of) a protein (an exon), or (2) not expressed as protein (an
      intron).

PMID- 7584432
TI  - Neural net representations of empirical protein potentials.
AB  - Recently, there has been considerable interest in deriving and applying knowledge
      based, empirical potential functions for proteins. These empirical potentials
      have been derived from the statistics of interacting, spatially neighboring
      residues, as may be obtained from databases of known protein crystal structures.
      In this paper we employ neural networks to redefine empirical potential functions
      from the point of view of discrimination functions. This approach generalizes
      previous work, in which simple frequency counting statistics are used on a
      database of known protein structures. This generalization allows us to avoid
      restriction to strictly pairwise interactions. Instead of frequency counting to
      fix adjustable parameters, one now optimizes an objective function involving a
      neural network parameterized probability distribution. We show how our method
      reduces to previous work in special situations, but also allows extensions to
      include orders of interaction beyond pairwise interaction. Given the close
      packing of proteins, steric interactions etc., the inclusion of higher order
      interactions is critical for developing an accurate potential. A key feature in
      the approach we advocate is the development of a representation to describe the
      spatial location of interacting residues that exist in a sphere of small fixed
      radius around each residue. This is a "shape representation" problem that has a
      natural solution for the interaction neighborhoods of protein residues. We
      demonstrate in a series of numerical experiments that the neural network approach
      improves discrimination over that obtained by previous methodologies limited to
      pair-wise interactions.

PMID- 7584436
TI  - Evaluating regularizers for estimating distributions of amino acids.
AB  - This paper makes a quantitative comparison of different methods, called
      regularizers, for estimating the distribution of amino acids in a specific
      context, given a very small sample of amino acids from that distribution. The
      regularizers considered here are zero-offsets, pseudocounts, substitution
      matrices (with several variants), and Dirichlet mixture regularizers. Each
      regularizer is evaluated based on how well it estimates the distributions of the
      columns of a multiple alignment--specifically, the expected encoding cost per
      amino acid using the regularizer and all possible samples from each column. In
      general, pseudocounts give the lowest encoding costs for samples of size zero,
      substitution matrices give the lowest encoding costs for samples of size one, and
      Dirichlet mixtures give the lowest for larger samples. One of the substitution
      matrix variants, which added pseudocounts and scaled counts, does almost as well
      as the best known Dirichlet mixtures, but with a lower computation cost.

PMID- 7584435
TI  - 3-D lookup: fast protein structure database searches at 90% reliability.
AB  - There are far fewer classes of three-dimensional protein folds than sequence
      families but the problem of detecting three-dimensional similarities is NP
      complete. We present a novel heuristic for identifying 3-D similarities between a
      query structure and the database of known protein structures. Many methods for
      structure alignment use a bottom-up approach, identifying first local matches and
      then solving a combinatorial problem in building up larger clusters of matching
      substructures. Here, the top-down approach is to start with the global comparison
      and select a rough superimposition using a fast 3-D lookup of secondary structure
      motifs. The superimposition is then extended to an alignment of C alpha atoms by
      an iterative dynamic programming step. An all-against-all comparison of 385
      representative proteins (150,000 pair comparisons) took 1 day of computer time on
      a single R8000 processor. In other words, one query structure is scanned against
      the database in a matter of minutes. The method is rated at 90% reliability at
      capturing statistically significant similarities. It is useful as a rapid
      preprocessor to a comprehensive protein structure database search system.

PMID- 7584434
TI  - Constituting a receptor-ligand information base from quality-enriched data.
AB  - Many different resources are needed for analyzing relevant experimental data in
      drug design. Currently this data is difficult to access, because it is stored in
      heterogeneous databases, spread over many platforms, poorly interconnected,
      incomplete, erroneous, or just not electronically available. In order to
      establish a high quality database for drug design we have developed a new demand
      driven methodology for integrating and semantically enriching heterogeneous data
      from different research areas and for migrating the data into an object-oriented
      database management system. In this way we have established a database containing
      well-prepared, relevant data needed for drug design and offering the advantages
      of modern database technology, like a comprehensive object-oriented data model, a
      flexible declarative query language and support for persistent storage and
      sharing of data in a multi-user environment.

PMID- 7584437
TI  - Computer tool FUNSITE for analysis of eukaryotic regulatory genomic sequences.
AB  - We present the computer tool FUNSITE for description and analysis of regulatory
      sequences of eukaryotic genomes. The tool consists of the following main parts:
      1) An integrated database for genomic regulatory sequences. The integrated
      database was designed on the basis of the databases TRANSFAC (Wingender 1994) and
      TRRD (Kel et al. 1995) that are currently under development. The following
      functions are performed: i) linkage to the EMBL database; ii) preparing samples
      of definite types of functional sites with their flanking sequences; iii)
      preparing samples of promoter sequences; iv) preparing samples of transcription
      factors classified with regard to structural and functional features of DNA
      binding and activating domains, functional families of the factors, their tissue
      specificity and other functional features; v) access to data on mutual
      disposition of cis-elements within the regulatory regions. 2) The second
      component of FUNSITE tool is the set of programs for analysis of the structural
      organization of regulatory sequences: i) Program for revealing of potential
      transcription factors binding sites based on their consensi; ii) program for
      revealing of the potential binding sites using homology search with nucleotide
      sequences of real binding sites; iii) program for analysis of oligonucleotide
      context features which are characteristic of flank sequences of the binding
      sites; iv) program for design of recognition method for the functional sites
      based on generalized weight matrix; v) program for revealing potential composite
      elements. The results of analysis of the promoter sequences of eukaryotic genes
      with the FUNSITE are presented, too.

PMID- 7584438
TI  - Identification of cDNA sequences by specific oligonucleotide sets. Computer tool
      and application.
AB  - A computer tool has been developed for revealing sets of oligonucleotides
      invariant for isofunctional families of DNA (RNA) and for using these in
      functional identification of nucleotide sequences. The tool allows one to: build
      up vocabularies of invariant oligonucleotides for the families of isofunctional
      nucleotide sequences; assess significance of the vocabularies; identify
      nucleotide sequences with the vocabularies of invariant oligonucleotides;
      determine the most effective identification parameters to minimize first and
      second type errors; assess the efficiency of identification of individual
      isofunctional families with the oligonucleotide vocabularies; determine the
      evolutionary characteristics of the families of isofunctional sequences on which
      vocabulary volume depends. Based on the system mentioned, we have analyzed a
      total of 322 protein-encoding gene families and have built up sets of invariant
      oligonucleotides, or again, oligonucleotide vocabularies that are characteristic
      of gene families and subfamilies. Identification of nucleotide sequences
      belonging to these families with the sets of invariant oligonucleotides revealed
      has been shown. Under the most effective identification parameters, the first
      type error (false negative) on control (independent) data was 10-15%, the second
      type error (false positive) was just 1-2 redundant sequences per sequence being
      examined. As has been shown, the volume of a vocabulary of invariant
      oligonucleotides depends on the percentage of variable positions in the multiple
      alignment within a family.

PMID- 7584439
TI  - The value of prior knowledge in discovering motifs with MEME.
AB  - MEME is a tool for discovering motifs in sets of protein or DNA sequences. This
      paper describes several extensions to MEME which increase its ability to find
      motifs in a totally unsupervised fashion, but which also allow it to benefit when
      prior knowledge is available. When no background knowledge is asserted. MEME
      obtains increased robustness from a method for determining motif widths
      automatically, and from probabilistic models that allow motifs to be absent in
      some input sequences. On the other hand, MEME can exploit prior knowledge about a
      motif being present in all input sequences, about the length of a motif and
      whether it is a palindrome, and (using Dirichlet mixtures) about expected
      patterns in individual motif positions. Extensive experiments are reported which
      support the claim that MEME benefits from, but does not require, background
      knowledge. The experiments use seven previously studied DNA and protein sequence
      families and 75 of the protein families documented in the Prosite database of
      sites and patterns, Release 11.1.

PMID- 7584442
TI  - A constraint-based assignment system for automating long side chain assignments
      in protein 2D NMR spectra.
AB  - The sequential assignment of protein 2D NMR data has been tackled by many
      automated and semi-automated systems. One area that these systems have not
      tackled is the searching of the TOCSY spectrum looking for cross peaks and
      chemical shift values for hydrogen nuclei that are at the end of long side
      chains. This paper describes our system for solving this problem using constraint
      logic programming and compares our constraint satisfaction algorithm to a
      standard backtracking version.

PMID- 7584443
TI  - Relation between protein structure, sequence homology and composition of amino
      acids.
AB  - A method of quantitative comparison of two classifications rules applied to
      protein folding problem is presented. Classification of proteins based on
      sequence homology and based on amino acid composition were compared and analyzed
      according to this approach. The coefficient of correlation between these
      classification methods and the procedure of estimation of robustness of the
      coefficient are discussed.

PMID- 7584441
TI  - An optimized parsing algorithm well suited to RNA folding.
AB  - The application of stochastic context-free grammars to the determination of RNA
      foldings allows a simple description of the sub-class of sought secondary
      structures, but it needs efficient parsing algorithms. The more classic
      thermodynamic model of folding, popularized by Zuker under the framework of
      dynamic programming algorithms, allows an easy computation of foldings but its
      use is delicate when constraints have to be introduced on sought secondary
      structures. We show here that S-attribute grammars unify these two models and we
      introduce a parsing algorithm whose efficiency enables us to handle problems
      until then too difficult or too large to deal with. As a matter of fact, our
      algorithm is as efficient as a standard dynamic programming one when applied to
      the thermodynamic model (yet it offers a greater flexibility for the expression
      of constraints) and it is faster and saves more space than other parsing
      algorithms used so far for stochastic grammars.

PMID- 7584440
TI  - Maximum entropy weighting of aligned sequences of proteins or DNA.
AB  - In a family of proteins or other biological sequences like DNA the various
      subfamilies are often very unevenly represented. For this reason a scheme for
      assigning weights to each sequence can greatly improve performance at tasks such
      as database searching with profiles or other consensus models based on multiple
      alignments. A new weighting scheme for this type of database search is proposed.
      In a statistical description of the searching problem it is derived from the
      maximum entropy principle. It can be proved that, in a certain sense, it corrects
      for uneven representation. It is shown that finding the maximum entropy weights
      is an easy optimization problem for which standard techniques are applicable.

PMID- 7584445
TI  - MMDB: an ASN.1 specification for macromolecular structure.
AB  - We present an exchange specification for data describing the three-dimensional
      structure of biological macromolecules. The specification was designed for MMDB,
      a Molecular Modeling Database supported by the National Center for Biotechnology
      Information (NCBI), based on information from the Protein Data Bank (PDB). In the
      MMDB specification, the chemical structures of molecules are described
      hierarchically as connectivity graphs, to directly support comparison by subgraph
      isomorphism or assignment algorithms. Three-dimensional coordinates are linked
      unambiguously to nodes in the chemical graph, so that homology-derived structures
      may be generated directly from alignment of chemically similar groups. In
      conversion to this form, data from PDB are extensively validated, so as to
      provide a description of chemical and spatial structure that is as accurate as
      possible. These changes in format and content of the known structure data are
      intended to support development of intelligent molecular modeling applications
      that make use of this invaluable information resource.

PMID- 7584444
TI  - Cooperative computer system for genome sequence analysis.
AB  - Analysis of the huge volumes of data generated by large scale sequencing projects
      clearly requires the construction of new sophisticated computer systems. These
      systems should be able to handle the biological data as well as the results of
      the analysis of this data. They should also help the user to choose the most
      appropriate method for a simple task and to string together the methods needed to
      solve a global analysis task. In this paper we present the prototype of a
      software system that provides an environment for the analysis of large-scale
      sequence data. In a first approach this environment has been put to the test
      within the B. subtilis sequencing project. This system integrates both a
      descriptive knowledge of the entities involved (genes, regulatory signals etc.)
      and the methodological knowledge concerning an extendable set of analytical
      methods (i.e. how to solve a sequence analysis problem through task decomposition
      and method selection). A knowledge representation based on two existing object
      oriented models, named Shirka and SCARP, is used to implement this integrated
      system. In addition, the present prototype provides a suitable user interface for
      both displaying the results generated by several methods and interacting with the
      objects. We present in this paper an overview of the knowledge-based models used
      to build this integrated system, and a description of the way in which biological
      entities and sequence analysis tasks are represented. We give illustrations of
      the co-operation between user and system during the problem solving process. Such
      a system constitutes a computer workbench for molecular biologists studying the
      genetic programs of living organisms.

PMID- 7584446
TI  - Softening constraints in constraint-based protein topology prediction.
AB  - This paper is concerned with the handling of uncertain data about the
      applicability of constraints in protein topology prediction. It discusses the use
      of novel methods of representing and reasoning with uncertain data, and presents
      the results of some experiments in using these methods to build probabilistic
      models of constraint application. It thus builds on work by other authors in both
      constraint satisfaction and probabilistic reasoning.

PMID- 7584447
TI  - DNA sequence assembly and genetic algorithms new results and puzzling insights.
AB  - Applying genetic algorithms to DNA sequence assembly is not a straightforward
      process. Significantly improved results in terms of performance, quality of
      results, and the scaling of applicability have been realized through non-standard
      and even counter-intuitive parameter settings. Specifically, the solution time
      for a 10kb data set was reduced by an order of magnitude, and a 20kb data set
      that was previously unsolved by the genetic algorithm was solved in a time that
      represents only a linear increase from the 10kb data set. Additionally,
      significant progress has been made on a 35kb data set representing real
      biological data. A single contig solution was found for a 752 fragment subset of
      the data set, and a 15 contig solution was found for the full data set. This
      paper discusses the new results, the modifications to the previous genetic
      algorithm used in this study, the experimental design process by which the new
      results were obtained, the questions raised by these results, and some
      preliminary attempts to explain these results.

PMID- 7584449
TI  - Investigations of Escherichia coli promoter sequences with artificial neural
      networks: new signals discovered upstream of the transcriptional startpoint.
AB  - In this paper we present a novel method for using the learning ability of a
      neural network as a measure of information in local regions of input data. Using
      the method to analyze Escherichia coli promoters, we discover all previously
      described signals, and furthermore find new signals that are regularly spaced
      along the promoter region. The spacing of all signals correspond to the helical
      periodicity of DNA, meaning that the signals are all present on the same face of
      the DNA helix in the promoter region. This is consistent with a model where the
      RNA polymerase contacts the promoter on one side of the DNA, and suggests that
      the regions important for promoter recognition may include more positions on the
      DNA than usually assumed. We furthermore analyze the E. coli promoters by
      calculating the Kullback Leibler distance, and by constructing sequence logos.

PMID- 7584450
TI  - Protein docking combining symbolic descriptions of molecular surfaces and grid
      based scoring functions.
AB  - With the growing number of known 3D protein structures, computing systems, that
      can predict where two protein molecules interact with each other is becoming of
      increasing interest. A system is presented, integrating preprocessing like the
      computation of molecular surfaces, segmentation, and searching for
      complementarity in the general framework of a pattern analyzing semantic network
      (ERNEST). The score of coarse symbolic computations is used by the problem
      independent control strategy of ERNEST to guide a more detailed analysis
      considering steric clash and judgements based on grid-based surface
      representations. Successful examples of the docking system are discussed that
      compare well with other approaches.

PMID- 7584448
TI  - A new approach to primer selection in polymerase chain reaction experiments.
AB  - We address the problem of primer selection in polymerase chain reaction (PCR)
      experiments. We prove that the problem of minimizing the number of primers
      required to amplify a set of DNA sequences is NP-complete, and show that even
      approximating solutions to this problem to within a constant factor times optimal
      is intractable. On the practical side, we give a simple branch-and-bound
      algorithm that solves the primers minimization problem within reasonable time for
      typical instances. We present an efficient approximation scheme for this problem,
      and prove that our heuristic always produces solutions no worse than a
      logarithmic factor times the optimal, this being the best approximation possible
      within polynomial time. Finally, we analyze a weighted variant, where both the
      number of primers as well as the sum of their "costs" is optimized
      simultaneously. We conclude by presenting the empirical performance of our
      methods on biological data.

PMID- 7584451
TI  - Periodic sequence patterns in human exons.
AB  - We analyse the sequential structure of human exons and their flanking introns by
      hidden Markov models. Together, models of donor site regions, acceptor site
      regions and flanked internal exons, show that exons--besides the reading frame-
      hold a specific periodic pattern. The pattern, which has the consensus: non
      T(A/T)G and a minimal periodicity of roughly 10 nucleotides, is not a consequence
      of the nucleotide statistics in the three codon positions, nor of the well known
      nucleosome positioning signal. We discuss the relation between the pattern and
      other known sequence elements responsible for the intrinsic bending or curvature
      of DNA.

PMID- 7584452
TI  - Time-efficient docking of flexible ligands into active sites of proteins.
AB  - We present an algorithm for placing flexible molecules in active sites of
      proteins. The two major goals in the development of our docking program, called
      FLEXX, are the explicit exploitation of molecular flexibility of the ligand and
      the development of a model of the docking process that includes the physico
      chemical properties of the molecules. The algorithm consists of three phases: The
      selection of a base fragment, the placement of the base fragment in the active
      site, and the incremental construction of the ligand inside the active site.
      Except for the selection of the base fragment, the algorithm runs without manual
      intervention. The algorithm is tested by reproducing 11 receptor-ligand complexes
      known from X-ray crystallography. In all cases, the algorithm predicts a
      placement of the ligand which is similar to the crystal structure (about 1.5 A
      RMS deviation or less) in a few minutes on a workstation, assuming that the
      receptor is given in the bound conformation.

PMID- 7584453
TI  - Subclass approach for mutational spectrum analysis.
AB  - Analysis and comparison of mutational spectra represents a burning question in
      molecular biology. We report an algorithm based upon the SEM subclass approach
      (SEM--stochastique, estimations, maximizations). Any real mutational spectrum is
      regarded as a mixture of standard binomial distributions. The separation
      procedure is run by rounds. Each iteration includes simulation, maximization and
      estimation. The algorithm has been checked on random spectra with the preset
      parameters and on real mutational spectra. As has been shown, any real mutational
      spectrum can be represented as a mixture of two and more binomial distributions,
      of which one contains hotspots of mutation.

PMID- 7584454
TI  - TOPITS: threading one-dimensional predictions into three-dimensional structures.
AB  - Homology modelling, currently, is the only theoretical tool which can
      successfully predict protein 3D structure. As 3D structure is conserved in
      sequence families, homology modelling allows to predict 3D structure for 20% of
      SWISSPROT. 20% of the proteins in PDB are remote homologues to another PDB
      protein. Threading techniques attempt to predict such remote homologues based on
      sequence information. Here, a new threading method is presented. First, for a
      list of PDB proteins, 3D structure was projected onto 1D strings of secondary
      structure and relative solvent accessibility. Then, secondary structure and
      accessibility were predicted by neural network systems (PHD). Finally, the
      predicted and observed 1D strings were aligned by dynamic programming. The
      resulting alignment was used to detect remote 3D homologues. Four results stand
      out. Firstly, even for an optimal prediction (assignment based on known
      structure), only about half the hits that ranked above a given threshold were
      correctly identified as remote homologues; only about 25% of the first hits were
      correct. Secondly, real predictions (PHD) were not much worse: about 20% of the
      first hits were correct. Thirdly, a simple filtering procedure improved
      prediction performance to about 30% correct first hits. The correct hit ranked
      among the first three for more than 23 out of 46 cases. Fourthly, the combination
      of the 1D threading and sequence alignments markedly improved the performance of
      the threading method TOPITS for some selected cases.

PMID- 7584456
TI  - Using temporal reasoning for genome map assembly.
AB  - Genomic maps are an indispensable tool for molecular biologists; their modelling
      has to take into account representation as well as computational issues. The
      algorithmic complexity of the assembly task is already huge and is even made
      worse when one wishes to deal with inconsistencies and provide generic tools.
      This work presents an algorithm tackling the assembly problem by using temporal
      reasoning techniques. The algorithm has to transform the initial input data, i.e.
      qualitative and quantitative relations between entities that appear on the maps,
      so that temporal reasoning algorithms can be applied successfully; this is
      achieved by performing a partition of these relations upon their relative
      orientation, creating islets of relations in which reasoning mechanisms are
      applied. The implementation of the algorithm is based on a temporal reasoning
      software, taken as is, which gives a high genericity since any improvement in
      this software (such as efficiency or the management of flexible constraints) can
      be immediately used by the algorithm.

PMID- 7584455
TI  - A distance-based block searching algorithm.
AB  - We present in this paper an algorithm for the multiple comparison of a set of
      protein sequences. Our approach is that of peptide matching and consists in
      looking for all the words that occur approximatively in at least q of the
      sequences in the set, where q is a parameter. Words are compared by using a
      reference object called a model, that is itself a word over the alphabet of the
      amino acids, and the comparison between a model and a word is based on w-length
      words instead of single symbols. This idea is similar to the one used in the
      Blast program in the case of pairwise comparisons. Two w-length words are
      considered to be related if an alignment without gaps of the two using a
      similarity matrix has a score greater than a certain threshold value t. In our
      case, we say that a k-length word u is an occurrence of a model m of the same
      length if every w-length subword of u is related to the corresponding subword of
      m in the sense given above. If a model m has occurrences in at least q of the
      sequences of the set, m is said to occur in the set. In percentage terms, the
      value of q may correspond to something as small as 5% of the sequences (search
      for recurrent words in a set of non homologous proteins) or as high as 70-100%
      (establishment of a list of all similar words as a first step in a multiple
      alignment program). The algorithm presented here is an efficient and exact way of
      looking for all the models, of a fixed length k or of the greatest possible
      length kmax, that occur in a set of sequences. It can work with any kind of
      scoring matrix and an extension of the algorithm allows for the introduction of
      gaps between a model and its occurrences.

PMID- 7584457
TI  - Automata-theoretic models of mutation and alignment.
AB  - Finite-state automata called transducers, which have both input and output, can
      be used to model simple mechanisms of biological mutation. We present a
      methodology whereby numerically-weighted versions of such specifications can be
      mechanically adapted to create string edit machines that are essentially
      equivalent to recurrence relations of the sort that characterize dynamic
      programming alignment algorithms. Based on this, we have developed a visual
      programming system for designing new alignment algorithms in a rapid-prototyping
      fashion.

PMID- 7584458
TI  - Solvent accessible surface representation in a database system for protein
      docking.
AB  - Protein docking is a new and challenging application for query processing in
      database systems. Our architecture for an efficient support of docking queries is
      based on the multistep query processing paradigm, a technique well-known from
      spatial database system. Along with physicochemical parameters, the geometry of
      the molecules plays a fundamental role for docking retrieval. Thus, 3D structures
      and 3D surfaces of molecules are basic objects in molecular databases. We specify
      a molecular surface representation based on topology, define a class of
      neighborhood queries, and sketch some applications with respect to the docking
      problem. We suggest a patch-based data structure called the TriEdge structure,
      first, to efficiently support topological query processing, and second, to save
      space in comparison to common planar graph representations such as the quad-edge
      structure. In analogy to the quad-edge structure, the TriEdge structure has an
      algebraic interface and is implemented via complex pointers. However, we achieve
      a reduction of the space requirement by a factor of four. Finally, we investigate
      the time performance of our prototype.

PMID- 7584459
TI  - BONSAI Garden: parallel knowledge discovery system for amino acid sequences.
AB  - We have developed a machine discovery system BONSAI which receives positive and
      negative examples as inputs and produces as a hypothesis a pair of a decision
      tree over regular patterns and an alphabet indexing. This system has succeeded in
      discovering reasonable knowledge on transmembrane domain sequences and signal
      peptide sequences by computer experiments. However, when several kinds of
      sequences are mixed in the data, it does not seem reasonable for a single BONSAI
      system to find a hypothesis of a reasonably small size with high accuracy. For
      this purpose, we have designed a system BONSAI Garden, in which several BONSAI's
      and a program called Gardener run over a network in parallel, to partition the
      data into some number of classes together with hypotheses explaining these
      classes accurately.

PMID- 7584460
TI  - Identification of human gene structure using linear discriminant functions and
      dynamic programming.
AB  - Development of advanced technique to identify gene structure is one of the main
      challenges of the Human Genome Project. Discriminant analysis was applied to the
      construction of recognition functions for various components of gene structure.
      Linear discriminant functions for splice sites, 5'-coding, internal exon, and 3'
      coding region recognition have been developed. A gene structure prediction system
      FGENE has been developed based on the exon recognition functions. We compute a
      graph of mutual compatibility of different exons and present a gene structure
      models as paths of this directed acyclic graph. For an optimal model selection we
      apply a variant of dynamic programming algorithm to search for the path in the
      graph with the maximal value of the corresponding discriminant functions.
      Prediction by FGENE for 185 complete human gene sequences has 81% exact exon
      recognition accuracy and 91% accuracy at the level of individual exon nucleotides
      with the correlation coefficient (C) equals 0.90. Testing FGENE on 35 genes not
      used in the development of discriminant functions shows 71% accuracy of exact
      exon prediction and 89% at the nucleotide level (C = 0.86). FGENE compares very
      favorably with the other programs currently used to predict protein-coding
      regions. Analysis of uncharacterized human sequences based on our methods for
      splice site (HSPL, RNASPL), internal exons (HEXON), all type of exons (FEXH) and
      human (FGENEH) and bacterial (CDSB) gene structure prediction and recognition of
      human and bacterial sequences (HBR) (to test a library for E. coli contamination)
      is available through the University of Houston, Weizmann Institute of Science
      network server and a WWW page of the Human Genome Center at Baylor College of
      Medicine.

PMID- 7584461
TI  - Towards an intelligent system for the automatic assignment of domains in globular
      proteins.
AB  - The automatic identification of protein domains from coordinates is the first
      step in the classification of protein folds and hence is required for databases
      to guide structure prediction. Most algorithms encode a single concept based and
      sometimes do not yield assignments that are consistent with the generally
      accepted perception. Our development of an automatic approach to identify
      reliably domains from protein coordinates is described. The algorithm is
      benchmarked against a manual identification of the domains in 284 representative
      protein chains. The first step is the domain assignment by distance (DAD)
      algorithm that considers the density of inter-residue contacts represented in a
      contact matrix. The algorithm yields 85% agreement with the manual assignment.
      The paper then considers how the reliability of these assignments could be
      evaluated. Finally the use of structural comparisons using the STAMP algorithm to
      validate domain assignment is reported on a test case.

PMID- 7584462
TI  - Recursive dynamic programming for adaptive sequence and structure alignment.
AB  - We propose a new alignment procedure that is capable of aligning protein
      sequences and structures in a unified manner. Recursive dynamic programming (RDP)
      is a hierarchical method which, on each level of the hierarchy, identifies
      locally optimal solutions and assembles them into partial alignments of sequences
      and/or structures. In contrast to classical dynamic programming, RDP can also
      handle alignment problems that use objective functions not obeying the principle
      of prefix optimality, e.g. scoring schemes derived from energy potentials of mean
      force. For such alignment problems, RDP aims at computing solutions that are near
      optimal with respect to the involved cost function and biologically meaningful at
      the same time. Towards this goal, RDP maintains a dynamic balance between
      different factors governing alignment fitness such as evolutionary relationships
      and structural preferences. As in the RDP method gaps are not scored explicitly,
      the problematic assignment of gap cost parameters is circumvented. In order to
      evaluate the RDP approach we analyse whether known and accepted multiple
      alignments based on structural information can be reproduced with the RDP method.
      For this purpose, we consider the family of ferredoxins as our prime example. Our
      experiments show that, if properly tuned, the RDP method can outperform methods
      based on classical sequence alignment algorithms as well as methods that take
      purely structural information into account.

PMID- 7584463
TI  - Protein modeling with hybrid Hidden Markov Model/neural network architectures.
AB  - Hidden Markov Models (HMMs) are useful in a number of tasks in computational
      molecular biology, and in particular to model and align protein families. We
      argue that HMMs are somewhat optimal within a certain modeling hierarchy. Single
      first order HMMs, however, have two potential limitations: a large number of
      unstructured parameters, and a built-in inability to deal with long-range
      dependencies. Hybrid HMM/Neural Network (NN) architectures attempt to overcome
      these limitations. In hybrid HMM/NN, the HMM parameters are computed by a NN.
      This provides a reparametrization that allows for flexible control of model
      complexity, and incorporation of constraints. The approach is tested on the
      immunoglobulin family. A hybrid model is trained, and a multiple alignment
      derived, with less than a fourth of the number of parameters used with previous
      single HMMs. To capture dependencies, however, one must resort to a larger hybrid
      model class, where the data is modeled by multiple HMMs. The parameters of the
      HMMs, and their modulation as a function of input or context, is again calculated
      by a NN.

PMID- 7584464
TI  - Neweyes: a system for comparing biological sequences using the running Karp-Rabin
      Greedy String-Tiling algorithm.
AB  - A system for aligning nucleotide or amino acid biosequences is described. The
      system, called Neweyes, employs a novel string matching algorithm. Running Karp
      Rabin Greedy String Tiling (RKR-GST), which involves tiling one string with
      matching substrings of a second string. In practice, RKR-GST has a computational
      complexity that appears close to linear. With RKR-GST, Neweyes is able to detect
      transposed substrings or substrings of one biosequence that appears rearranged in
      a second sequence. Repeated substrings can also be detected. Neweyes also
      supports a form of matching-by-group that gives the effect of different amino
      acid mutation matrices. Neweyes can be used in a macro mode (searching a database
      for a list of biosequences that are similar to a given biosequence) or in a micro
      mode, where two biosequences are compared and more detailed output formats are
      available.

PMID- 7584465
TI  - Identification of protein motifs using conserved amino acid properties and
      partitioning techniques.
AB  - Analyzing a set of protein sequences involves a fundamental relationship between
      the coherency of the set and the specificity of the motif that describes it.
      Motifs may be obscured by training sets that contain incoherent sequences, in
      part due to protein subclasses, contamination, or errors. We develop an algorithm
      for motif identification that systematically explores possible patterns of
      coherency within a set of protein sequences. Our algorithm constructs alternative
      partitions of the training set data, where one subset of each partition is
      presumed to contain coherent data and is used for forming a motif. The motif is
      represented by multiple overlapping amino acid groups based on evolutionary,
      biochemical, or physical properties. We demonstrate our method on a training set
      of reverse transcriptases that contains subclasses, sequence errors,
      misalignments, and contaminating sequences. Despite these complications, our
      program identifies a novel motif for the subclass of retroviral and retrovirus
      related reverse transcriptases. This motif has a much higher specificity than
      previously reported motifs and suggests the importance of conserved hydrophilic
      and hydrophobic residues in the structure of reverse transcriptases.

PMID- 7584466
TI  - Viewing genome data as objects for application development.
AB  - Genomics is becoming a data-intensive science, and an increasing number of
      laboratories are generating data which swamps storage in traditional paper-and
      ink notebooks. Capturing the data flow requires large systems with multiple
      applications manipulating the same or similar data. Large systems often have
      conflicting requirements for data representation. Consistency across applications
      is a prime consideration, and appropriate data representation is an important
      issue in developing practical systems for molecular biologists. Graphs are a
      natural representation for describing genome data, while objects are good for
      modeling the behavior necessary for laboratory applications. We present a method
      for translating graph descriptions of genome data into objects using objects as
      views on graphs. Graph representations describe genome concepts while objects
      capture individual views for application development insuring consistency across
      genome applications.

PMID- 7584467
TI  - APIC: a generic interface for sequencing projects.
AB  - In this paper, we describe the APIC graphical interface that aims at displaying
      the results produced by the genomic sequence analysis methods and at helping a
      comparison of these results. The major feature of APIC lies in its genericity. As
      a matter of fact, this interface can obviously be used to visualise genetic or
      physical maps but it also able to display other kinds of information such as
      curves or pictures. On the one hand, APIC provides the biologist who builds a new
      sequence analysis method with a standard interface allowing to display his
      results. Thus, he can avoid implementing a specific visualisation tool. On the
      other hand, even when the methods already have their own interfaces, using APIC
      has the advantage of giving a homogeneous way to compare several results coming
      from different analysis tools. Moreover, it provides some powerful functions for
      navigating and browsing into the results.

PMID- 7584468
TI  - A specification for defining and annotating regions of macromolecular structures.
AB  - We present a program- and machine-independent standard for annotating
      macromolecular structures. Data encoded by this specification may be used for
      communicating information about structures and for exchanging it between
      different computer systems. The format consists of a set of ASN.1 objects which
      are mechanically straightforward to parse, but are also easy for humans to create
      and understand. It differs from all other related standards in that it specifies
      how a molecule should be displayed without requiring a custom format for the
      coordinate data.

PMID- 7584469
TI  - Graph-theoretic approach to RNA modeling using comparative data.
AB  - We have examined the utility of a graph-theoretic algorithm for building
      comparative RNA models. The method uses a maximum weighted matching algorithm to
      find the optimal set of basepairs given the mutual information for all pairs of
      alignment positions. In all cases examined, the technique generated models
      similar to those based on conventional comparative analysis. Any set of pairwise
      interactions can be suggested including pseudoknots. Here we describe the details
      of the method and demonstrate its implementation on tRNA where many secondary and
      tertiary base-pairs are accurately predicted. We also examine the usefulness of
      the method for the identification of shared structural features in families of
      RNAs isolated by artificial selection methods such as SELEX.

PMID- 7584470
TI  - Predicting free energy contributions to the conformational stability of folded
      proteins from the residue sequence with radial basis function networks.
AB  - Radial basis function neural networks are trained on a data base comprising 38
      globular proteins of well resolved crystallographic structure and the
      corresponding free energy contributions to the overall protein stability (as
      computed partially from chrystallographic analysis and partially with multiple
      regression from experimental thermodynamic data by Ponnuswamy and Gromiha
      (1994)). Starting from the residue sequence and using as input code the
      percentage of each residue and the total residue number of the protein, it is
      found with a cross-validation method that neural networks can optimally predict
      the free energy contributions due to hydrogen bonds, hydrophobic interactions and
      the unfolded state. Terms due to electrostatic and disulfide bonding free
      energies are poorly predicted. This is so also when other input codes, including
      the percentage of secondary structure type of the protein and/or residue-pair
      information are used. Furthermore, trained on the computed and/or experimental
      delta G values of the data base, neural networks predict a conformational
      stability ranging from about 10 to 20 kcal mol-1 rather independently of the
      residue sequence, with an average error per protein of about 9 kcal mol-1.

PMID- 7584471
TI  - Recognising promoter sequences using an artificial immune system.
AB  - We have developed an artificial immune system (AIS) which is based on the human
      immune system. The AIS possesses an adaptive learning mechanism which enables
      antibodies to emerge which can be used for classification tasks. In this paper,
      we describe how the AIS has been used to evolve antibodies which can classify
      promoter containing and promoter negative DNA sequences. The DNA sequences used
      for teaching were 57 nucleotides in length and contained procaryotic promoters.
      The system classified previously unseen DNA sequences with an accuracy of
      approximately 90%.

PMID- 7584472
TI  - Predicting protein folding classes without overly relying on homology.
AB  - An important open problem in molecular biology is how to use computational
      methods to understand the structure and function of proteins given only their
      primary sequences. We describe and evaluate an original machine-learning approach
      to classifying protein sequences according to their structural folding class. Our
      work is novel in several respects: we use a set of protein classes that
      previously have not been used for classifying primary sequences, and we use a
      unique set of attributes to represent protein sequences to the learners. We
      evaluate our approach by measuring its ability to correctly classify proteins
      that were not in its training set. We compare our input representation to a
      commonly used input representation--amino acid composition--and show that our
      approach more accurately classifies proteins that have very limited homology to
      the sequences on which the systems are trained.

PMID- 7584473
TI  - Extracellular matrix 1: Fibril-forming collagens.

PMID- 7584475
TI  - Directed cytokine expression in tumour cells in vivo using recombinant vaccinia
      virus.
AB  - Athymic (Swiss nude) and euthymic (DBA) tumour-bearing mice were injected
      intravenously with various vaccinia virus (Copenhagen strain) recombinants.
      Several days after inoculation, tumour cells were found to be well infected with
      infective vaccinia particles, while organs such as liver, spleen, brain and bone
      marrow showed barely detectable levels or no signs at all of virus infection.
      Injection of tumour bearing mice with recombinant VV harbouring the cDNA for
      either huIL-2 or muIL-6 resulted in detectable lymphokine in the sera of injected
      animals. Injection of tumour-bearing nude mice with VV-IL-6, but not with VV-IL
      2, resulted in significant reduction in growth rate of the tumour, and in some
      cases, complete rejection of the tumour. Tumour-bearing euthymic mice responded
      differently. Intravenous injection of VV-IL-2, but not VV-IL-6 resulted in
      reduced growth rate of 50% of tumours and complete rejection of 17% of tumours.

PMID- 7584474
TI  - Actin-binding proteins. 1: Spectrin super family.

PMID- 7584476
TI  - Interaction of tumour necrosis factor-alpha and radiation against human colon
      tumour cells.
AB  - Recent reports demonstrating that the lethal effects of radiation on tumour cells
      can be augmented by tumour necrosis factor-alpha (TNF-alpha) prompted us to
      investigate whether this premise holds true for the LS174T human colon
      adenocarcinoma cell line. Three different techniques were used to assess cell
      damage: 3H-thymidine (3H-TdR) uptake, clonogenic survival, and vital dye
      exclusion. In these assays human recombinant TNF-alpha treatment was administered
      before single-dose-gamma-radiation at 4, 6, 8, or 10 Gy. Oxygen radical formation
      by the tumour cells in the presence of TNF-alpha and radiation, alone and in
      combination, was also investigated. TNF-alpha and radiation, when used as single
      modalities, decreased LS174T cell viability with time. However, treatment with
      TNF-alpha before irradiation resulted in highly significant reductions in 3H-TdR
      uptake and decreased clonogenic survival compared to their counterparts receiving
      only radiation. Our data show that these two measurements of tumour-cell damage
      correlate well. No difference was noted in vital dye exclusion when comparisons
      were made between TNF-alpha+radiation and radiation alone. This latter finding
      may be partly due to the fact that although apoptotic cells are 'dead', they
      generally do not become more permeable to normally excluded macromolecules.
      Chemiluminescence measurements indicate that the radiation-enhancing mechanism of
      TNF-alpha may be related to oxygen radical production by the LS174T cells. Taken
      together our results suggest that TNF-alpha may be useful as an adjunctive
      modality in the radiotherapy of colon cancer.

PMID- 7584477
TI  - Single-chain mono- and bispecific antibody derivatives with novel biological
      properties and antitumour activity from a COS cell transient expression system.
AB  - Single-chain antibody molecules were expressed from modified eukaryotic
      expression vectors as individual protein domains encoded on interchangeable cDNA
      cassettes. Two different single-chain antibody derivatives were constructed by
      linking individual light- and heavy-chain variable domains. The first was
      specific for the L6 tumour-associated antigen and the second was specific for
      human CD3. Each single-chain variable domain was genetically fused with an Fc
      'tag' and expressed as a fusion protein in a COS cell transient transfection
      system. These single-chain antibody derivatives demonstrated specific binding to
      cells expressing appropriate antigen and bound with affinities similar to native
      antibody. The CD3 single chain molecule mediated stronger activation of PLC gamma
      1 and similar levels of T-cell proliferation compared with native antibody. A
      bispecific Fv single-chain cassette was created by fusing the expression
      cassettes encoding the binding domains for L6 and CD3 single-chain molecules
      using oligonucleotide primers encoding a short 27-residue 'helical' peptide
      linker. The CD3-L6 variable domains were fused to the Fc tag and expressed in COS
      cells. The CD3-L6FvIg bispecific fusion protein mediated adhesion between T cells
      and L6-positive tumour cells, and stimulated potent T-cell proliferation and
      cytotoxicity against tumour cells expressing the L6 antigen.

PMID- 7584478
TI  - New immunosuppressive drugs--pharmacologic approaches to alter immunoregulation.

PMID- 7584479
TI  - Xenograft rejection--molecular mechanisms and therapeutic implications.
AB  - The rejection of a vascularized xenograft between phylogenetically distant
      species is a result of natural antibody binding to the graft endothelium and the
      activation of complement. The subsequent dysfunction of endothelial cell
      physiology results in the loss of vascular integrity and ultimately the failure
      of the graft. Strategies aimed at preventing the initial steps of antibody
      binding and complement activation have successfully prevented hyperacute
      rejection in experimental models resulting in a significant prolongation of
      xenograft survival. The rapidly increasing understanding of the mechanisms of
      xenograft rejection, and the potential ability to counter these mechanisms using
      recent advances in molecular biology, immunology, and vascular biology, provide
      encouragement that discordant xenotransplantation may prove clinically
      applicable.

PMID- 7584480
TI  - Humanized immunotoxins.

PMID- 7584482
TI  - Induction of donor-specific tolerance by transplantation of bone marrow.

PMID- 7584481
TI  - Immunospecific drug design--prospects for treatment of autoimmune diseases.
AB  - Recent advances in elucidating the activation and regulation of the autoimmune
      processes have provided new approaches for selective immunotherapy. Three
      different strategies are described: autoantigen-based therapy utilizing
      immunospecifically designed macromolecules and peptides, T-suppressor lines and
      clones, as well as antibodies specific to the antigen-MHC complex. These
      modalities, the efficacy of which has been demonstrated for experimental allergic
      encephalomyelitis, may be adapted to other experimental as well as human
      autoimmune diseases.

PMID- 7584484
TI  - Lymphocyte development in genetically manipulated mice.

PMID- 7584485
TI  - Human recombinant TNF-alpha on localization of 90Y-radioantibody in human tumour
      xenografts.
AB  - The effect of recombinant human tumour necrotic factor-alpha (TNF-alpha) on the
      intratumour and whole-body distributions of 90Y-labelled C110
      anticarcinoembryonic antigen (CEA) monoclonal antibody (MAb) was studied using
      nude mice bearing two different tumours. The nude mice were injected
      subcutaneously with the CEA-positive LS174T colorectal cancer xenograft and the
      CEA-negative H-MESO-1 malignant mesothelioma xenograft. One hour before injection
      of radiolabelled MAb, mice were injected intravenously with human recombinant TNF
      alpha (3 mg per mouse) or saline, and biodistributions of radiolabel were
      determined by tissue counting and whole-body autoradiography (ARG). Twenty-four
      hours after injection, TNF-alpha administration increased radioactivity in the
      LS174T tumour by 57% (17.30 +/- 1.61 vs. 9.83 +/- 1.55% ID g-1, P < 0.01), while
      decreasing radioactivity in blood and other normal organs. Diminished but similar
      effects on radioantibody biodistribution were seen at 48 and 72 hours. TNF-alpha
      did not affect specific MAb localization in the control H-MESO xenograft.
      Tumour:blood ratios were increased from 0.7 to 1.7 at 24 h with TNF-alpha
      administration. Pretreatment with TNF-alpha may be of value in increasing
      specific localization of monoclonal antibodies in tumour tissue.

PMID- 7584483
TI  - Interleukin-I antagonists.

PMID- 7584487
TI  - The production and preclinical characterization of a chimeric anti-breast-cancer
      antibody, cBC2.
AB  - A chimeric (mouse-human) BC2 antibody (cBC2) was produced which may be used in
      the diagnosis and treatment of breast cancer. The BC2 variable region genes were
      amplified by polymerase chain reaction (PCR), using oligonucleotide primers
      homologous to the framework sequences of mouse VH and V kappa genes. The PCR
      products were used to create cBC2 expression vectors containing the mouse BC2 VH
      and V kappa and human constant region (IgG1 and K) genes. Chimeric antibody was
      produced following transfection of these constructs into Sp2/0 myeloma cells.
      Binding assays in vitro demonstrated that cBC2 had the same specificity for human
      milk fat globule membrane (HMFGM) and MUC1+ cells as mBC2, and bound antigen with
      a similar affinity (cBC2, Ka 5.53 +/- 2.09 x 10(8); mBC2, Ka 1.44 +/- 0.98 x
      10(9)). Functionally, only cBC2 (5-25 micrograms ml-1), was able to mediate
      antibody-dependent cellular cytotoxicity (ADCC) with human effector cells, with
      25% maximal specific lysis of MUC1+ cells at an E/T ratio of 100:1. Human
      complement-mediated lysis was minimal (10-15% specific lysis) with both mBC2 and
      cBC2. Neither cBC2 nor mBC2 was able to inhibit tumour growth in vivo in the
      absence of covalently coupled anticancer drugs. However, biodistribution studies
      demonstrated that both antibodies preferentially targeted MUC1+ tumour cells,
      with 17% of the injected dose of cBC2, as compared to 27% of mBC2, localized to
      the MUC1+ tumour at 24 h (less than 6% detected in any other tissue).

PMID- 7584486
TI  - Evaluation of anti-CD5 ricin A chain immunoconjugate for prevention of acute
      graft-vs.-host disease after HLA-identical marrow transplantation.
AB  - Anti-CD5 ricin A chain immunoconjugate (XZ-CD5) is an immunotoxin that inhibits
      proliferative and cytotoxic responses to alloantigen in vitro and has activity in
      the treatment of acute graft-vs.-host disease (GVHD). To determine if XZ-CD5
      could be used to prevent acute GVHD, 11 adult recipients of HLA-identical
      allogeneic marrow received XZ-CD5 0.1 mg kg-1 day-1 intravenously with high-dose
      methyl-prednisolone for 10, 14 or 17 doses early post-transplant. Six additional
      patients received 17 doses of XZ-CD5 and cyclosporine (CSA). All patients
      engrafted. Severe capillary leak syndrome was the most common serious toxicity
      and occurred more frequently in patients receiving CSA (5/5 vs. 3/11, P = 0.03).
      All evaluable patients developed acute GVHD; 88% had grade II-IV GVHD. Flow
      cytometric analysis demonstrated a substantial number of circulating CD5+ and
      CD3+ lymphocytes during and early after administration of XZ-CD5. These results
      suggest that the immunotoxin did not eliminate alloreactive T cells in this
      setting.

PMID- 7584488
TI  - The status of HIV/AIDS vaccines--1993.

PMID- 7584489
TI  - The effects of FK506 and dexamethasone on rat thymocyte differentiation.
AB  - We investigated the effects of FK506 and glucocorticoids (GC) on rat thymocytes
      using flow cytofluorometry. Rats were treated with GC (0.1 mg/body, by single
      injection), with FK506 (1 mg/kg/day, for 7 days), or with FK506 and GC. GC alone
      significantly decreased the percentage of CD4+8+ thymocytes and increased the
      percentages of CD4-8-, CD4+8- and CD4-8+ thymocytes on day 7. FK decreased the
      percentage of CD4+8- and CD4-8+ thymocytes and increased the percentage of CD4+8+
      thymocytes on days 5 to 14. FK and GC induced a significant decrease in the
      number of CD4+8+ thymocytes greater than that seen with GC alone on day 7. The
      absolute number of TCR alpha beta high MHC class Ihigh thymocytes after FK and GC
      was significantly lower than that of the control group, and was slightly lower
      than that after FK alone on day 14. These results suggest that combined treatment
      with FK506 and GC acts complexly to decrease rat CD4+8+ thymocytes and prevents
      thymocyte differentiation and maturation.

PMID- 7584490
TI  - Rapid induction of cytolytic T cells via CD28 stimulation for cellular
      immunotherapy.
AB  - One approach to adoptive cancer immunotherapy is based on the use of bispecific
      monoclonal antibodies (mAb) capable to redirect ex vivo generated cytolytic T
      lymphocytes (CTL) onto tumour cells. The efficiency of the CD28 T-cell activation
      pathway to induce CD3-dependent cytolytic activity was investigated while
      avoiding modulation of the TCR/CD3 complex needed for targeting by bispecific
      mAb. When used e.g. in conjunction with anti-CD2 antibodies or diacylglycerol
      derivatives, the in vitro stimulation of T cells with anti-CD28 mAb resulted
      within 36 h in high levels of CD3-dependent cytolysis (tested on a FcR+ target in
      the presence of anti-CD3 mAb) and sustained lymphokine production, such as TNF
      alpha, IFN gamma and IL-2, which may affect tumour growth when delivered locally
      by the transferred T cells. Rapid activation may reduce costly in vitro
      procedures, preserve homing capacities of retransfused T cells, and thus
      facilitate implementation of clinical trials based on the use of bispecific
      antibodies.

PMID- 7584492
TI  - Blocking of adhesion molecules in vivo as anti-inflammatory therapy.

PMID- 7584493
TI  - Interleukin-10 and its receptor.
AB  - The cytokine interleukin-10 (IL-10) has several important activities on cells of
      the immune system. IL-10 profoundly suppresses activation of macrophages,
      inhibiting their ability to secrete cytokines and serve as accessory cells for
      stimulation of T cell and natural killer (NK) cell function. IL-10 also plays a
      role in stimulating proliferation and differentiation of B cells, mast cells, and
      both mature and immature T cells. At least two herpesviruses harbor analogs of
      the IL-10 gene; the Epstein-Barr virus (EBV) homolog (BCRF1, viral IL-10, vIL-10)
      shares several of the cellular cytokine's activities, one or all of which may be
      important in the host-virus relationship. This article reviews recent studies on
      the function of IL-10 and discusses the initial characterization of its receptor.

PMID- 7584494
TI  - Interleukin-12: a cytokine with therapeutic potential in oncology and infectious
      diseases.
AB  - IL-12 is a cytokine that promotes cell-mediated immunity by promoting Th1-type
      cytokine responses, enhancing the lytic activity of NK/LAK cells, augmenting
      specific CTL responses, and inducing the production of IFN-gamma. On the other
      hand, IL-12 suppresses the development of Th2-type cytokine responses and humoral
      immunity, particularly IgGl and IgE responses. It is likely that IL-12 normally
      plays an important role in the host defense against intracellular microbial
      pathogens. In addition, the administration of rIL-12 to mice has been shown to
      have potent therapeutic effects in several tumour and infectious disease models.
      IL-12 has been shown to be more efficacious than IL-2 in several murine tumour
      models, and toxicology studies suggest that it may have a substantially better
      therapeutic index. In addition, the long serum half-life of IL-12 relative to
      other cytokines will allow more flexibility in dosing schedules. However, future
      clinical trials are required to determine whether the efficacy of IL-12 seen in
      these experimental models is predictive for its use as an immunomodulatory drug
      in humans.

PMID- 7584495
TI  - Degradation of ricin A chain by endosomal and lysosomal enzymes--the protective
      role of ricin B chain.
AB  - We investigated the role of intracellular processing of ricin A chain (RTA) by
      proteolytic enzymes on the expression of its ribosome inhibitory activity.
      Endosomal and lysosomal proteases extracted from Jurkat cells and purified
      cathepsins B, D and G were incubated with RTA, resulting in generation of a 28
      kDa fragment by proteolytic cleavage. This process was reminiscent of the nicking
      of Pseudomonas exotoxin and Diphtheria toxin by intracellular proteases to
      produce functionally active toxin fragments. However, the ribosome inhibitory
      activity of the purified 28-kDa fragment of RTA was 11,000-fold less than that of
      native RTA, suggesting that such cleavage is not an essential step in the
      cytotoxic activity of the toxin. Addition of ricin B chain (RTB) in degradation
      assays resulted in the protection of RTA from proteolytic activities of lysosomes
      and cathepsins. However, RTB did not protect another RNA acting protein, RNAase;
      nor did excess amounts of unlabeled RTA or IgG protect labelled RTA from
      degradation, suggesting that the protective effect of RTB was specific to its
      interaction with RTA. Such a protective role for RTB may partially account for
      the higher toxicity of immunotoxins (ITs) containing whole ricin compared to ITs
      containing only RTA.

PMID- 7584496
TI  - The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates.
AB  - LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3
      fused to the hinge, CH2 and CH3 domains of human IgG1, inhibits proliferation of
      human T cells in vitro. LFA3TIP also inhibits responses of human CD2 transgenic
      mice by rapidly and totally depleting peripheral T cells. These effects require
      binding of the LFA-3 and CH2 domains of LFA3TIP to CD2+ T cells and Fc gamma R+
      accessory cells, respectively. As CD2 is well conserved in primate species, we
      evaluated the effects of LFA3TIP in nonhuman primates. We report in vitro results
      leading to the selection of the baboon as a model for analysis of LFA3TIP, and in
      vivo effects of single and multidose regimens of LFA3TIP administration. This is
      the first report of the in vivo administration of an immunomodulatory fusion
      protein to primates. LFA3TIP is shown to mediate effects on primate T lymphocytes
      without apparent related toxicities or immunogenicity. Results are discussed in
      context of potential mechanisms of LFA3TIP immunotherapy.

PMID- 7584497
TI  - The CD28 costimulatory pathway.

PMID- 7584491
TI  - Xenobiotics, chimerism and the induction of tolerance following organ
      transplantation.
AB  - The successful results seen after organ transplantation are largely attributable
      to the potency and specificity of modern immunosuppressive agents. Although drug
      free unresponsiveness to graft alloantigens has not been routinely achieved in
      clinical practice, recent appreciation of the importance of cell chimerism, which
      develops after the migration from donor to host of leukocytes contained in solid
      organ grafts, has introduced a concept which may explain the mechanism of graft
      tolerance. Recent evidence has indicated that immunosuppressive drugs may have a
      common potential to induce graft tolerance, even though they act through diverse
      mechanisms, and that this potential may be mediated by a permissive effect on the
      migration and survival of donor-derived leukocytes. This review briefly examines
      the mechanisms by which immunosuppressive drugs function and analyses the
      different methods which these agents might use to induce chimerism associated
      with graft tolerance. Furthermore, we describe ongoing clinical studies in which
      the chimerism produced after solid organ transplantation is augmented with donor
      bone marrow in an attempt to facilitate the induction of tolerance.

PMID- 7584498
TI  - Chemokines, inflammation and the immune system.
AB  - The chemokine superfamily comprise two families of small secreted proteins that,
      with the exception of RANTES, beta-TG, and PF-4, are not expressed in resting
      cells but are rapidly induced in response to various inflammatory and mitogenic
      stimuli. These proteins function as chemoattractants and activating agents for
      inflammatory cells. At present, it appears that each of the chemokines have some
      activities that are unique and many that are overlapping. Important areas that
      still need to be unravelled are the signal transduction pathways that lead to
      induction of these genes and the identification of the serpentine receptors and
      signal transduction pathways that are activated by these proteins. alpha and beta
      chemokines are implicated as major participants in acute as well as chronic
      inflammatory reactions, inhibition of haematopoeisis, modulation of angiogenesis,
      and fibroplasia. Chemokines that act on T lymphocytes presumably influence the
      recruitment of immunocompetent cells to inflammatory sites. Although there is no
      evidence that chemokines play a role in the induction of immune reactions, they
      undoubtedly promote the effector limb of immunity. The likely possibility that
      chemokines may also contribute to the normal homing and distribution of
      leukocytes also needs to be evaluated. Although chemokines obviously have major
      differentiative effects on the functions of target cells, the possibility that
      they act as costimulants of cell growth also needs more study. Finally,
      chemokines are attractive targets for the development of new therapeutic agents.
      Inhibition of their activities may be an effective anti-inflammatory strategy;
      promoting their activity might enhance wound healing and tissue repair.

PMID- 7584499
TI  - Engineering multiple-domain forms of the therapeutic antibody CAMPATH-1H: effects
      on complement lysis.
AB  - Antibody-mediated lysis of cells involves a complex interaction between the cell,
      the target antigen, the antibody and host effector mechanisms. One such
      mechanism, complement-mediated cell lysis, requires the interaction of C1q with
      the antibody heavy chain constant regions, and in particular the CH2 domain. Here
      we investigate the potential benefit of multiple-domain forms of the therapeutic
      monoclonal antibody CAMPATH-1H. This antibody is directed against the CDw52
      antigen expressed by human lymphocytes and has proven lytic abilities both in
      vitro and in vivo. Using target cells with either high or low antigen density,
      engineered antibodies that contained additional domains in tandem (CH2, hinge-CH2
      or Fc intramolecular repeats) showed no improvement in complement-mediated lysis
      when compared with controls. However, a homodimeric form of the antibody that was
      engineered by mutation of a serine residue to cysteine near the carboxy-terminal
      of the CH3 domain, exhibited markedly improved lysis using target cells
      expressing antigen at low density. Interestingly, no improvement was seen using
      cells expressing antigen at high density. These results suggest that dimeric
      forms of antibodies could be useful for converting cells with low density
      antigens into useful targets for therapy.

PMID- 7584500
TI  - The regulation of lymphoid function during schistosomiasis: influence of T-cell
      derived suppressor molecules on antigen recognition, cellular activation and
      granuloma formation.
AB  - We have previously studied a T-cell derived soluble suppressor factor (TseF)
      which regulates immunopathology in schistosomiasis. The current studies address
      the mechanism whereby TseF suppresses the functional immune response in murine
      schistosomiasis. We assessed three stages of the immune response: (1) initial
      antigenic recognition using the criteria of antigen-mediated cell division or
      blast transformation (AMBT); (2) intracellular differentiation utilizing criteria
      of glutathione (GSH) and ornithine decarboxylase (ODC) production; and (3)
      efferent function utilizing criteria of in vitro granuloma formation (IVGF). We
      studied these three criteria of immune reactivity during the course of
      schistosomiasis. Lymphoid cells from acutely infected animals demonstrated high
      levels of antigen-mediated cell division and in vitro granuloma formation; ODC
      and GSH levels were low. Cells obtained from chronically infected animals
      demonstrated lower antigen-mediated cell division and granuloma formation;
      however, ODC and GHS levels were much higher, indicating that cells obtained from
      chronically infected animals are in a non-reactive state of increased activation.
      TseF strongly increased GSH and ODC levels in lymphocytes obtained from acutely
      infected animals, and this effect was augmented by the presence of antigen.
      However, TseF had minimal effects on initial antigenic recognition, and
      profoundly suppressed the effector function. The relationship between the effects
      of TseF on antigen recognition and function was regulated at the clonal level.
      TseF function required the generation of GSH. Since TseF is produced in chronic
      disease under conditions of decreased immunological reactivity, the alterations
      of GSH and ODC activity, induced by TseF, may be responsible for the regulation
      of immunopathology.

PMID- 7584501
TI  - Anti-CD4 activity of normal human immunoglobulin G for therapeutic use.
      (Intravenous immunoglobulin, IVIg).
AB  - The effects of intravenously administered normal immunoglobulin G (IVIg) in
      autoimmune diseases are dependent on the ability of IVIg to interact with surface
      molecules of lymphocytes. In the present study, we demonstrate the presence of
      anti-CD4 activity in IVIg by showing the ability of IVIg to bind to CD4 and to
      inhibit CD4-dependent cellular functions. Binding of IVIg to recombinant soluble
      human CD4 was assessed by ELISA, immunoblotting and real time analysis of complex
      formation. Anti-CD4 antibodies isolated from IVIg by affinity-chromatography
      bound to human CD4+ T cells. These anti-CD4 antibodies inhibited proliferative
      responses in MLR and infection of CD4+ human T cells with HIV. These results
      indicate that IVIg contains antibodies reactive with human CD4 and that these
      anti-CD4 antibodies exhibit biological functions. The presence of anti-CD4
      antibodies in IVIg may be relevant to the immunoregulatory effects of normal
      polyspecific immunoglobulin G.

PMID- 7584502
TI  - Evaluation of Fc gamma receptor mediated T-cell activation by two purified CD3 x
      CD19 bispecific monoclonal antibodies with hybrid Fc domains.
AB  - Two bispecific monoclonal antibodies (BsAb), differing in H chain isotype
      combination, were made for treatment of B-cell leukaemia/lymphoma; QAI-2, CD3
      mouse-IgG1 x CD19-mouse-IgG2a and QAI-3, CD3-mouse-IgG1 x CD19-mouse-IgG2b. Both
      purified BsAb proved equally effective for their ability to target pre-activated
      T cells towards CD19 positive tumour cells. In T-cell proliferation assays, the
      capacity of Fc gamma RIa (CD64), Fc gamma RIIa-R131 and Fc gamma RIIa-H131 (CD32)
      transfected fibroblasts was tested to present the BsAb. The BsAb combining mouse
      (m) IgG1 and mIgG2a promoted T-cell activation in combination with the Fc gamma
      RIa transfectant; the mIgG1-mIgG2b BsAb was only marginally active. Both BsAb
      could not induce T-cell activation when presented by either of the Fc gamma RIIa
      transfectants. Similar results were obtained using PBMC cultures, containing Fc
      gamma RIa+/Fc gamma RIIa+ monocytes as accessory cells. The importance of Fc
      gamma R-dependent BsAb-mediated T-cell activation emerged from experiments with T
      cells and CD19 positive B-cell lines, showing that cross-linking via CD19+ target
      cells alone did not induce T-cell proliferation. Therefore, BsAb with
      functionally different Fc domains represent alternative strategies in BsAb
      therapy, the efficacy of which deserves to be compared in vivo.

PMID- 7584504
TI  - Role of cell-mediated immunity in bovine leukemia virus (BLV) infection in
      ruminants: its implication for the vaccination strategy against retroviruses.
AB  - Recent studies in the immunopathogenesis of bovine leukemia virus (BLV) infection
      in ruminants, reviewed herein, provide an insight into the vaccination strategy
      against retrovirus infection. It was shown that vaccination of naive sheep with a
      recombinant vaccinia virus (RVV) expressing BLV envelope glycoprotein protected
      the animals against BLV infection. The involvement of cell-mediated immunity
      (CMI) in this phenomenon was strongly suggested. The postinfection vaccination,
      that is, the vaccination of BLV-infected animals with RVV, also significantly
      suppressed BLV replication in the carrier animals. These findings support the
      idea that vaccination against retroviruses should put its emphasis on the
      induction of CMI and that such vaccine could be used not only for prophylactic
      but also for therapeutic purposes.

PMID- 7584503
TI  - Considerations in the design and production of small anti-receptor antibody
      forms: optimizing gains while reducing size.
AB  - Recent advances which have lead to the cloning of numerous immunoglobulin genes
      has resulted in the production of a variety of recombinant small antibody-like
      molecules. These smaller immunoglobulin derived molecules have potential for the
      development of diagnostic and pharmaceutical compounds. The considerations in the
      design and production of smaller antibody-like molecules and their clinical
      applications will be summarized in this review.

PMID- 7584505
TI  - Helplessness as a strategy for avoiding antiglobulin responses to therapeutic
      monoclonal antibodies.
AB  - The antiglobulin (anti-Ig) response to therapeutic monoclonal antibodies (mAbs)
      poses a significant obstacle to their routine application in man. Whilst
      humanization has lessened the problem, repeated courses of humanized mAbs still
      sensitise some patients. Previous work suggested that unresponsiveness to cell
      binding (therapeutic) mAbs could not be achieved due to an unexpected
      immunogenicity of their idiotypes (ids). The current work examines this
      phenomenon in more detail using CBA/Ca mice receiving rat antimouse CD8 mAbs as a
      model system. It is shown that the anti-Ig response is dependent on CD4+ T-cells.
      Furthermore, for at least some mAbs, most helper epitopes appear to reside within
      the mAb c-region. Consequently, when tolerance is induced to c-region (isotype),
      the anti-id response is extremely weak (induced helplessness). For one (weakly
      immunogenic) CD8 mAb concomitant administration of a CD4 mAb was sufficient to
      induce tolerance, whereas for another (more immunogenic) CD8 mAb, tolerance could
      only be achieved by prior concomitant exposure to both a CD4 mAb and an isotype
      matched non-cell-binding mAb. The general applicability of these results is
      discussed and extrapolated to the clinical situation. Non-cell-binding variants
      of therapeutic mAbs could be usefully exploited to generate therapeutic
      unresponsiveness to any clinically useful mAb.

PMID- 7584506
TI  - Suppressive effect of cyclophosphamide on the progression of lethal graft-versus
      host disease in mice--a therapeutic model of fatal post-transfusion GVHD.
AB  - In this paper, we examine in a murine system whether cyclophosphamide (CY) could
      prevent the development of fatal GVHD and furthermore whether it could be used to
      treat on-going GVHD. (C57BL/6xDBA/2)F1 (BDF1) mice were injected with spleen
      cells from B6 donors and their thoraces were opened to mimic cardiac operation.
      These mice lost body weight gradually and most of them died during 2-4 weeks post
      transfusion. They showed splenomegaly, thymic atrophy and marked bone-marrow
      aplasia. When CY was administered at 100 mg kg-1 on days 0, 2, 7 and 9, all mice
      were relieved of GVHD and their organs were almost free of signs of GVHD. CY (100
      mg kg-1) administered on days 7 and 9 also save mice from lethal GVHD. Moreover,
      CY administered at a dose of 20 mg kg-1 on days 9 and 11 when GVHD became
      apparent was also effective. These data suggest that CY might be used as a
      therapeutic agent for lethal post-transfusion GVHD.

PMID- 7584508
TI  - Sparing of first dose effect of monovalent anti-CD3 antibody used in allograft
      rejection is associated with diminished release of pro-inflammatory cytokines.
AB  - The murine monoclonal antibody OKT3 is the best known of the anti-CD3 antibodies
      used for the prevention and treatment of renal allograft rejection. Use of this
      antibody is associated with improved graft outcome but it has a number of adverse
      effects thought to result from the massive release of pro-inflammatory cytokines.
      It has been postulated that OKT3 causes cytokine release because of cross-linking
      of CD3 molecules on the cell surface by bivalent anti-CD3 antibodies, such as
      OKT3, and the simultaneous binding of the Fc regions of these monoclonal
      antibodies to Fc receptors on other cells resulting in cell activation.
      Monovalent antibodies directed against the CD3 antigen should not, in theory,
      cause cell activation and cytokine release by this postulated mechanism. This
      study details the use of a monovalent anti-CD3 monoclonal antibody in the
      treatment of allograft rejection in five renal transplant recipients and
      documents the degree of TNF, IFN-g and IL6 release generated after antibody
      injection. Monovalent anti-CD3 monoclonal antibody reversed the rejection episode
      for which it was used and was well tolerated in all patients. TNF, IFN-g and IL6
      measurement showed that little pro-inflammatory cytokine release occurred after
      this drug. It is likely that the relative lack of side-effects of monovalent anti
      CD3 reflects the blunted release of pro-inflammatory cytokines. Monovalent anti
      CD3 monoclonal antibody may be a useful addition to the reagents available to
      treat allograft rejection.

PMID- 7584507
TI  - Induced regression of bovine papillomas by intralesional immunotherapy.
AB  - It has long been assumed that papilloma regression is mediated by immunological
      mechanisms which are probably cellular in nature. The potentiation of these
      responses may alter the course of papilloma progression. Certain strains of the
      bacterium Corynebacterium parvum (Propionibacterium acnes) have been shown to
      augment cellular immune mechanisms by increasing both macrophage and natural
      killer cell activity. This study involves the use of naturally occurring bovine
      papillomas to investigate the immune mechanisms involved in induced papilloma
      regression. Papillomas were treated by intralesional injection of a C. parvum
      suspension. Treated papillomas were biopsied at various stages of regression.
      Tissue samples were subjected to immunohistochemical staining to identify
      specific infiltrating cells. Results showed that intralesional administration of
      C. parvum was capable of inducing regression of bovine papillomas in 8-15 weeks.
      Immunological staining revealed that regression was associated with an increased
      number of CD8+ and gamma delta+ cells in the dermis, as well as a marked
      infiltration of neutrophils.

PMID- 7584509
TI  - Differential permeability of the blood-tumour barrier in intracerebral tumour
      bearing rats: antidrug antibody to achieve systemic drug rescue.
AB  - The feasibility of utilizing the differential permeability of the blood-tumour
      barrier to low- vs. high-molecular-weight compounds is demonstrated in a brain
      tumour model. Nude rats (n = 27) with or without intracerebral tumours received
      intravenous [3H]methotrexate (M(r) 454), followed 60 min later by
      antimethotrexate antibody (M(r) 150,000) or nonspecific mouse antibody.
      Antimethotrexate antibody resulted in 93% binding of serum methotrexate. In
      contrast, the percentage of antibody-bound methotrexate in brain and
      intracerebral tumour was only slightly greater than preantibody protein binding.
      Methotrexate delivery to tumour was significantly greater than to brain adjacent
      to tumour and normal brain. The percentage delivery of [3H]methotrexate to all
      areas of brain was similar between animals receiving antimethotrexate antibody
      and nonspecific antibody. These findings support the theory that a drug rescue
      method may be developed that may permit the safe administration of increased
      dosages of chemotherapeutic drugs for the treatment of intracerebral tumours.

PMID- 7584510
TI  - Better dead than red.

PMID- 7584512
TI  - Translocation of protein kinase C isozymes in rat pituitary lactotroph-enriched
      cell cultures by substance P: effects of sex and age.
AB  - It is generally accepted that the phospholipid and calcium-dependent enzyme
      protein kinase C (PKC) plays a significant role in secretion of hormones from
      anterior pituitary cells. The present study was undertaken to study age and sex
      related changes in 1. levels of immunoreactivity of PKC isozymes and 2.
      distribution of immunoreactivity of PKC isozymes after stimulation with substance
      P (SP) in rat lactotroph-enriched cell cultures. The alpha, beta, delta and zeta
      isozymes were present in both sexes and at all ages. There was a sex-specific
      differential regulation of the different PKC isozymes as a function of sexual
      maturation. In male rats there was an up-regulation of the alpha isozyme
      throughout the sexual development, while the beta subtype showed a small, but
      significant decrease in immunoreactivity with increasing age. In female rats, on
      the other hand, the beta species was up-regulated with increasing age while the
      other subtypes remained constant. The concentration of the delta and zeta
      isozymes was unaffected of sex and age. Stimulation of lactotroph-enriched cell
      cultures with substance P (SP) resulted in translocation of the alpha and beta
      isozymes from the soluble to the particulate fraction while the delta and zeta
      species were left unchanged independently of age and sex. However, a decrease in
      responsiveness was observed in adult male rats, although a significant degree of
      translocation of alpha and beta species was still detected. On the basis of these
      results it is suggested that in lactotroph-enriched cell cultures basal levels of
      PKC subtype immunoreactivity and distribution of immunoreactivity of PKC isozymes
      after SP challenge might be regulated as a function of sex and age.

PMID- 7584511
TI  - Diazepam biphasically modulates [3H]TBOB binding to the convulsant site of the
      GABAA receptor complex.
AB  - Interactions of GABA, bicuculline methochloride and diazepam with [3H]TBOB
      binding to rat brain membranes were evaluated in vitro. GABA displaced [3H]TBOB
      binding with and IC50 of 4 microM and a slope factor near unity. The competitive
      GABA antagonist bicuculline methochloride shifted the displacement curve of GABA
      parallelly to the right, indicating that the interaction of GABA with [3H]TBOB
      binding is of an allosteric nature. In the presence of GABA, diazepam displaced
      the binding of [3H]TBOB according to a two-site model: a high affinity site with
      an IC50 of about 50 nM and a lower affinity site with an IC50 of about 30 microM.
      Bicuculline methochloride abolished the nanomolar displacement by diazepam and
      increased the micromolar IC50 value. These results indicate that the interaction
      of the high affinity diazepam site with the [3H]TBOB binding site is totally GABA
      dependent and that the low affinity effect of diazepam on [3H]TBOB binding is at
      least partially GABA dependent. It is likely that the low affinity potency of
      diazepam to displace [3H]TBOB binding has physiological relevance.

PMID- 7584514
TI  - AMPA (amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors in human
      brain tissues.
AB  - AMPA receptors may play an important role in acute and chronic neurodegenerative
      diseases. An assay for the specific binding of [3H]-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) to receptors in membranes from post
      mortem human brain is described, which can be used in screening for selective
      AMPA receptor antagonists. Membranes were prepared from frozen human adult
      hippocampus and whole fetal brain tissues. [3H]-AMPA binding to human hippocampus
      was saturable; Scatchard analysis of equilibrium binding data indicated high and
      low affinity sites with affinity binding constants (KD) of 3.4 +/- 0.5 nM and 65
      +/- 9 nM (n = 7) respectively. Biphasic association and dissociation rate
      constants for [3H]-AMPA binding were consistent with the biphasic Scatchard
      analysis. Inhibition of [3H]-AMPA binding revealed a rank order of potency as
      quisqualate = AMPA > BOAA > L-glutamate = DNQX = CNQX > kainate > L-aspartate =
      NMDA. AMPA receptors in human fetal brain had a comparable pharmacology.
      AMPA/kainate receptors were expressed in frog oocytes following injection of RNA
      prepared from human fetal brain. Human brain tissues may therefore be utilized
      for screening and functional analysis of AMPA receptor antagonists.

PMID- 7584513
TI  - Subunit-specific redox modulation of NMDA receptors expressed in Xenopus oocytes.
AB  - We have examined the effects of oxidizing and reducing agents on a number of
      subtypes of N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes.
      Oocytes were injected with cRNA for the zeta 1 subunit from mouse to express
      homomeric receptors or with zeta 1 in combination with either epsilon 1, epsilon
      2, epsilon 3 or epsilon 4 subunits to express heteromeric receptors. All
      heteromeric combinations resulted in receptors that were affected by the redox
      reagents, dithiothreitol (DTT) and 5-5-dithio-bis-2-nitrobenzoic acid (DTNB).
      However, the effects on the small currents from homomeric receptors were quite
      variable. The zeta 1/epsilon 3 combination showed a greater enhancement by DTT
      than any of the other combinations. All four receptors expressed showed both a
      component of persistent potentiation and a slowly reversible component. The
      reversible component was largest for zeta 1/epsilon 3. Additional experiments
      were done with S-nitrosocysteine (SNOC), a nitric oxide donor that may affect
      NMDA receptors by oxidation. SNOC had transient effects on the four heteromeric
      subunit combinations. The different sensitivities of particular subunit
      combinations may have pharmacological and clinical significance.

PMID- 7584516
TI  - RT-PCR and alternative methods to PCR for in vitro amplification of nucleic
      acids.
AB  - The amplification of small amounts of nucleic acids via PCR (Mullis and Faloona,
      1985) has undergone a tremendous development in biology, biochemistry, clinical
      diagnosis, and related fields. The typical three step reaction consisting of heat
      denaturation, primer annealing, and primer elongation together with the advanced
      technology in the instrumentation of thermal cyclers has made the reaction simple
      and fast. The idea to use a heat stable DNA polymerase, primers, and dNTPs in
      order to amplify double stranded DNA molecules in an exponential manner is not
      the only way to produce large amounts of nucleic acids starting from a few
      molecules only. This paper will give an overview of some alternatives and their
      applications.

PMID- 7584519
TI  - Crude urinary human chorionic gonadotropin contains variant forms of HCG with low
      sialic acid content that exhibit an increased thyrotropic activity in CHO cells
      expressing the human TSH receptor.
AB  - Hyperthyroidism occurs in association with pregnancy or trophoblastic tumours.
      This is due to the secretion of thyroid stimulators by trophoblastic cells, most
      likely hCG or a variant form of hCG. In the present studies we sought to identify
      hCG variants with enhanced thyrotropic activity contained in crude hCG extract
      from pregnancy urine (hCGc). Such studies seem now feasible, because highly
      sensitive assays employing CHO cells transfected with the recombinant human TSH
      receptor recently became available. Initially, we found the activity of hCGc to
      both inhibit the binding of 125I-bTSH to CHO-TSHr cells and to stimulate the cAMP
      release by the cells to be increased, compared to highly purified hCG (hCGp),
      which was tested in comparable immunological concentrations. We then processed
      hCGc on a DEAE-52 anionexchange column to separate materials of interest, termed
      hCGv, from hCGp. HCGv was further purified by gel chromatography, and found to be
      enriched in terms of both, its holo-hCG immunoactivity and its TSH binding
      inhibiting activity, compared to hCGc where it was derived from. It also proved
      more potent than hCGp to bind to recombinant hTSH receptor and to stimulate
      adenylate cyclase activity in CHO-TSHr cells. Enzymatic desialylation was able to
      increase the potency of both hCGv and hCGp, and rendered the two desialylated hCG
      forms nearly equipotent. Isoelectric focusing and direct measurement of sialic
      acid contents revealed hCGv to be less sialylated than hCGp.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7584515
TI  - Gangliocytomas of the sellar region--a review.
AB  - Gangliocytomas are benign, slow growing neuronal tumors and are found for the
      most part in children and young adults. They are most often localized in either
      the spinal cord or the cerebral hemispheres. Gangliocytomas in the sellar region
      are extremely rare and only 43 such tumors (including 4 own cases) have ever been
      described in the literature. Although these tumors are genuine rarities without
      any epidemiological importance, they do provide some interesting information on
      tumorigenesis of pituitary adenomas: 65% of the sellar gangliocytomas are
      associated with a pituitary adenoma. 74% of patients with these tumors suffered
      hormonal oversecretion of at least one of the pituitary hormones (mostly growth
      hormone). With only one exception, the hypothalamic releasing hormone
      corresponding to the hormonal oversecretion syndrome could be demonstrated in the
      gangliocytoma immunohistochemically. Ultrastructural studies could demonstrate
      close cell to cell contacts between adenoma and gangliocytome cells. All these
      data support the hypothesis that chronic overstimulation by hypothalamic
      releasing hormones play a role in the development of hormone secreting pituitary
      adenomas. However, in contrast to sellar gangliocytemas, extrahypothalamic tumors
      secreting excessive hypothalamic hypophysiotropic hormones have never been
      associated with a pituitary adenoma. They have only been associated with
      pituitary cell hyperplasia. Therefore, the hypothesis can be made that
      hypothalamic releasing hormones only promote but do not initiate tumorigenesis of
      pituitary adenomas.

PMID- 7584517
TI  - Increase of serum insulin and stable c-peptide concentrations with exhaustive
      incremental graded exercise during acute hypoxia in sedentary subjects.
AB  - Hypoxia was shown to reduce insulin concentrations at rest and during exercise.
      However, some studies have also demonstrated increases in the hormone associated
      with arterial desaturation. This study was conducted in order to decide [1]
      whether acute alveolar hypoxia increased or decreased the circulating insulin
      levels, and [2] to elucidate whether interactions of insulin with other hormones
      were of relevance in this respect. Glucose (GLU), insulin (INS), c-peptide (CP),
      adrenaline and noradrenaline (CATs), atrial natriuretic peptide (ANP) and
      cortisol (CORT) as well as the capillary blood gases were determined in 15
      healthy fasting male volunteers (age: 26.2 +/- 2.8 years, body mass index: 22.4
      +/- 2.7 kg.m-2). On two separate test days the subjects breathed, in random
      order, either normal air (N) or a gas mixture with reduced oxygen content (H;
      FIO2: 0.14). Measurements were made at rest as well as during an incremental
      cycle exercise in a supine position (increments of 6 min and 50 W) at 100 W and
      150 W, at volitional exhaustion (N: 227 +/- 36 W; H: 200 +/- 32 W) as well as in
      the 5th min of recovery. Arterial desaturation was seen throughout on H-day. At
      rest all hormones and GLU were normal and showed no influence of H. During
      exercise INS remained constant on N-day, increased on H-day and was significantly
      higher with H than with N, most pronounced at 150 W and at volitional exhaustion
      with 20%, respectively. For CP and GLU no significant exercise-induced changes
      were seen on either test day and no influence of H was detected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584518
TI  - Potential of endogenous peptides to induce immunological reactions as observed in
      type I diabetes, a study in mice.
AB  - The initiation of the immunological processes leading to type I diabetes is still
      not understood. The potential of endogenous peptides to induce autoimmune
      reactions was investigated. Peptides generated in the beta-cell by proteolysis
      could bypass antigen processing by binding to MHC molecules. Selfreactive T and B
      lymphocytes could be activated by these MHC peptide complexes. The antibody
      production of peptide-induced B lymphocytes was investigated in mice. Insulin A
      chain, B chain, C-peptide or amylin were tested for potential induction of
      antibodies to antigens other than the immunizing peptide. Lymph node B
      lymphocytes were characterized with an avidin at solid phase ELISA-spot assay. In
      BALB/c mice insulin A chain induced more spots to B29biotin- and to B1biotinDOP
      insulin than to A chain itself (P < 0.01, each). Spots to insulin were not
      inhibited by insulin A chain. Spots to B1DOP insulin were not inhibited by A
      chain or insulin, excluding crossreaction. Inbred strains of mice with H-2d but
      not with H-2k or H-2b showed the effect. Application of A chain without adjuvant
      produced the effect. The antigens recognized by A chain-induced B lymphocytes had
      to be included in the natural IgM antibody repertoire of the spleen. The study
      supports the hypothesis that endogenous breakdown peptides can bypass antigen
      processing resulting in an autoreactive T-B cell interaction. A potential to
      induce type I diabetes could exist.

PMID- 7584520
TI  - The DNA and steroid binding domains of the glucocorticoid receptor are not
      altered in mononuclear cells of treated CLL patients.
AB  - The aim of this study was to investigate whether mutations in the glucocorticoid
      receptor could account for the increasing unresponsiveness of patients with
      chronic lymphatic leukemia (CLL) to combination chemotherapy. The receptor was
      tested immunocytochemically, in steroid binding assays, and by a mutation
      screening (denaturing gradient gel electrophoresis) of the receptor-cDNA. The
      receptor concentration, as measured by staining and steroid binding test, varied
      considerably but showed no clear correlation to clinical response. Using a highly
      sensitive mutation screening assay of the DNA- and the steroid-binding region,
      none of the treated patients revealed any mutation, suggesting that the
      glucocorticoid receptor in the CLL patients tested is not altered in these
      domains. In one individual who had not been treated before analysis a silent
      mutation was found in one receptor allele. The results suggest that mechanisms
      other than altered ligand or DNA binding of the receptor may be responsible for
      the lack of response to chemotherapy. This conclusion is discussed in relation to
      the mechanism of corticoid resistance in mouse and human lymphoma cells in
      culture.

PMID- 7584521
TI  - Changes in anterior pituitary response in patients with idiopathic hypothalamic
      hypogonadism caused by pulsatile GnRH therapy and testosterone replacement.
AB  - OBJECTIVE: This study evaluated in male patients with idiopathic hypothalamic
      hypogonadism the effect of pulsatile GnRH therapy or testosterone replacement on
      the response of all anterior pituitary hormones to adequate dynamic stimuli.
      PATIENTS AND DESIGN: In nine patients with idiopathic hypothalamic hypogonadism-
      mean age 21 +/- 1 (mean +/- SE)--a combined pituitary stimulation (CPS) with 200
      micrograms TRH, 100 micrograms GnRH, 100 micrograms CRH and 100 micrograms GRH
      and an insulin tolerance-test (ITT) with 0.1 U insulin/kg body weight were
      performed. Both tests were repeated during pulsatile GnRH therapy and thereafter
      on testosterone replacement. MEASUREMENTS: Hormone levels were measured by
      immunometric assays. For statistical analysis the area under the curve (AUC) was
      used as a measure for hormone response. RESULTS: Testosterone levels did not
      differ significantly during GnRH therapy (16.6 +/- 2.1 nmol/L) and testosterone
      replacement (18.5 +/- 1.7 nmol/L). No significant differences were observed
      before and during the two treatment modalities for TSH and ACTH. PRL increase was
      significantly higher during GnRH therapy (AUC: 73580 +/- 8940) compared to the
      rise before treatment (AUC: 36161 +/- 5853; p < 0.01) and on testosterone
      replacement (AUC: 49995 +/- 6158; p < 0.01). The GH response to CPS and ITT was
      higher under testosterone replacement (AUC: 1826 +/- 353 and 1423 +/- 125)
      compared with the pretreatment situation (AUC: 727 +/- 115; p < 0.05 and 541 +/-
      110; p < 0.01) and also more pronounced than under GnRH therapy (AUC: 1148 +/-
      180 and 798 +/- 129; p < 0.05). FSH and LH after CPS rose significantly more
      during GnRH therapy (AUC: 864 +/- 122 and 2215 +/- 219) than before (AUC: 418 +/-
      61 and 1424 +/- 277; p < 0.01) and on testosterone treatment (342 +/- 83 and 1153
      +/- 323; p < 0.05). CONCLUSION: These results show that GnRH exerts a stimulatory
      effect on PRL secretion and may modulate GH secretion independently from sex
      steroids.

PMID- 7584522
TI  - Antisense oligodeoxynucleotide complementary to oxytocin mRNA blocks lactation in
      rats.
AB  - The posterior lobe peptide oxytocin (OT) is known to control lactation and
      parturition, as well as maternal and sexual behavior. An antisense
      oligodeoxynucleotide (ODN) directed against the mRNA of OT was injected
      intracerebroventricularly 6 times in 12 hour intervals to manipulate the
      transcriptional message of OT in lactating rats. OT immunoreactivity in
      magnocellular hypothalamic nuclei and in the posterior lobe of the pituitary was
      reduced in antisense treated animals in comparison to ODN with scrambled base
      composition and vehicle controls. This decline in OT levels was associated with a
      decrease of pup weight. Our results demonstrate that central infusions of
      antisense ODN significantly reduce OT expression in vivo.

PMID- 7584524
TI  - Growth hormone secretion in response to the new centrally acting antihypertensive
      agent moxonidine in normal human subjects: comparison to clonidine and GHRH.
AB  - It is well established that the central alpha 2-adrenergic agonist clonidine can
      enhance growth hormone (GH) secretion in humans. This effect is most likely due
      to stimulation of hypothalamic growth hormone releasing hormone (GHRH) release.
      To determine the potency of the new I1-imidazoline receptor agonist moxonidine to
      release pituitary hormones, 12 normal volunteers received clonidine (0.3 mg),
      moxonidine (0.3 mg), or placebo orally according to a randomized, double-blind
      protocol. Blood was drawn prior and up to 180 min after drug administration for
      determination of GH, adrenocorticotropic hormone (ACTH), prolactin, thyrotropin
      (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), glucose,
      clonidine, and moxonidine concentrations. The results were compared to those
      obtained in a standard GHRH stimulation test (1 microgram/kg i.v.). Serum GH
      levels increased significantly in response to GHRH, clonidine, and moxonidine.
      However, the increase was less pronounced in response to clonidine and moxonidine
      as compared to GHRH (mean +/- SEM): after clonidine, GH increased from 0.2 +/-
      0.1 to 5.4 +/- 1.5 ng/ml, p < 0.05; moxonidine increased GH levels from 0.1 +/-
      0.04 to 4.8 +/- 1.9 ng/ml (p < 0.05); GHRH caused an increase from 0.01 +/- 0.05
      to 14.8 +/- 2.5 ng/ml (p < 0.05). No significant change was observed in the
      concentration of any other pituitary hormone. We conclude that the new I1
      imidazoline receptor agonist moxonidine stimulates GH release to a similar extent
      as clonidine.

PMID- 7584523
TI  - Time course of the effects of steroid hormone deprivation elicited by ovariectomy
      or ovariectomy plus adrenalectomy on the affinity and density of GABA binding
      sites in distinct rat brain areas.
AB  - The time course of the behaviour of GABAA receptors (affinity of muscimol for
      GABA binding sites and their number) in membranes obtained from five distinct rat
      brain areas was evaluated in dependence of the decline of the serum
      concentrations of estradiol and progesterone following hormone deprivation by
      either ovariectomy (OVX) or ovary- plus adrenalectomy (OVX-ADX) after 1, 2, 3, 5,
      14 and 30 days. Diestrus rats served as control. The effect of OVX on the GABA
      binding sites was due to a decrease of affinity rather than alterations in their
      density. Conversely, the combined surgery of OVX plus ADX affected both the
      affinity and the density. Also, the OVX-linked changes of muscimol binding were
      observed only after five days as compared to control animals, while the initial
      OVX-ADX associated changes occurred already after one day. OVX-ADX produced
      significant decreases in the number of binding sites at the shortest times
      investigated, in frontal cortex (FC) at day one and two and in the medulla
      oblongata (MED) after three days, which disappeared in the subsequent times
      studied. Concomitant with the major decrease of steroid hormone serum levels one
      day after OVX-ADX the FC displayed an increase in affinity by 45%. From the time
      when steroid serum levels are low the alterations in affinity elicited by both
      OVX-ADX and OVX only take a similar course, reflected by the following decrease
      in affinity. In MED an additional adrenalectomy did not significantly modify the
      OVX linked decrease of affinity, except that the initial effect was already
      evident two days after OVX-ADX.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584525
TI  - Total and free triiodothyronine in euthyroid individuals: the ambivalent
      influence of albumin in advanced age.
AB  - As T3 thyrotoxicosis may be difficult to be assessed in the low T3 syndrome and
      in advanced age, the matrix influence on different T3 parameters was evaluated in
      identical serum specimens of euthyroid non critically ill patients aged up to 95.
      The values obtained by the conventional TT3 RIA and the FT3 analog single step
      method with known albumin interference showed a strong relation to age (r =
      0.4877 and r = 0.6929, respectively; both p < 0.001). Free T3 measurement by a
      labeled monoclonal antibody technique was independent of age effects (r = 0.0324,
      p = 0.748). Upon analyzing the binding parameters, albumin decreased with age and
      correlated closely with the age dependent T3 parameters (TT3: r = 0.6610,
      apparent FT3 by analog: r = 0.7664; both p < 0.001). In identical specimens, FT3
      obtained by labeled monoclonal antibody is not influenced by albumin changes (r =
      0.1986, p = 0.063). Consequently, TT3 cannot exactly predict the thyrometabolic
      status without corrections regarding binding protein variation including albumin,
      which is the underlying cause of the age dependence. The FT3 assay using labeled
      monoclonal antibody represents a precise and convenient technique and gives
      reliable results independent of changes of binding protein.

PMID- 7584526
TI  - Perioperative management of the diabetic patient.
AB  - Patients with diabetes mellitus are at a higher risk to undergo surgical
      intervention compared with the non-diabetic population, and additionally, they
      have an increased perioperative morbidity and mortality. Insulin deficiency and
      insulin resistance are aggravated by surgery and anaesthesia. The consequences of
      hyperglycemia are glycosuria, volume depletion from osmotic diuresis, impairment
      of wound healing and leucocyte function and exacerbation of ischemic brain
      damage. Depending on the extent of hypoinsulinemia, lipolysis and ketogenesis are
      enhanced which may result in metabolic acidosis with subsequent electrolyte
      disturbances. Protein catabolism is increased because of increased breakdown and
      decreased synthesis. Insulin administration reverts or overcomes most of these
      disturbances. The preoperative assessment includes the diagnoses of the long-term
      complications to judge the intraoperative risks. Long-acting insulins, such as
      ultralente of animal origin should be stopped preoperatively and substituted by
      protamine and lente insulins. In type-2-diabetic patients, long-acting
      sulfonylurea drugs such as chlorpropamide should be stopped and substituted by
      short-acting agents. Metformin must always be stopped. Type-2-diabetic patients
      with marked hyperglycemia under oral treatment should be switched to insulin
      before operation. The insulin requirements in diabetic patients during surgery
      vary from 0.25-0.40 U per gram glucose in normal weight patients, 0.4-0.8 U per
      gram glucose in case of obesity, liver disease, steroid therapy or sepsis, to 0.8
      1.2 U per gram glucose in patients undergoing cardiopulmonary bypass surgery.
      Therefore, the appropriate dose has to be determined individually. The regimen
      nowadays preferred by most authors is based on variable rate insulin
      infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584527
TI  - Defects in the synthesis and metabolism of vitamin D.
AB  - It is now recognized that it is casual exposure to sunlight that provides most
      humans with their vitamin D requirement. During exposure to sunlight, the high
      energy ultraviolet B photons (290-315 mm) photolyzes cutaneous stores of 7
      dehydrocholesterol to previtamin D3. Once formed, previtamin D3 undergoes a
      thermal isomerization that results in the formation of vitamin D3. Vitamin D3 is
      biologically inert and requires successive hydroxylations in the liver and kidney
      to form its biologically active hormone 1,25-dihydroxyvitamin D3. The major
      physiologic function of 1,25-dihydroxy-vitamin D3 is to maintain blood calcium in
      the normal range. It accomplishes this by increasing the efficiency of intestinal
      calcium absorption and mobilizing stem cells to become osteoclasts which, in
      turn, remove calcium from the bone. It is now recognized that there are a variety
      of calcium metabolic disorders that are related to defects in the synthesis and
      metabolism of vitamin D. Chronic granulomatous disorders are often associated
      with hypercalciuria and hypercalcemia. The mechanism by which this occurs is that
      activated macrophages within granulomatous tissue, in an unregulated manner,
      convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Besides its calcemic
      activity 1,25-dihydroxyvitamin D3 is a potent antiproliferative factor for cells
      and tissues that possess its vitamin D receptor. This has clinical utility in
      that 1,25-dihydroxyvitamin D3 and its analogs have been successfully used for the
      treatment of the hyperproliferative skin disease psoriasis.

PMID- 7584528
TI  - Morphology and steroidogenesis of cultured granulosa cells from endometrioidally
      changed ovaries.
AB  - The aim of the study was to see the function of follicular cells collected from
      ovaries of women suffering from endometriosis. The material was granulosa cells
      taken from 11 patients operated on 3rd and 4th degree of endometriosis. Antral
      granulosa cells were harvested from 34 medium-size (5-10 mm in diameter)
      follicles located on the cysts' walls or in the cysts' vicinity. Using the
      culture method, morphology and steroid secretion was estimated. Morphological
      properties of the cells in the culture did not differ significantly from that of
      healthy ones. All cells formed a monolayer and achieved different degrees of
      luteinization. Steroidogenesis of these granulosa cells was defected,
      particularly in the production of progesterone and testosterone.

PMID- 7584529
TI  - Effects of corticotropin-releasing hormone on respiratory parameters during sleep
      in normal men.
AB  - Corticotropin-releasing hormone (CRH) is well-known to be a centrally acting
      respiratory stimulant after systemic application both in healthy subjects and in
      patients suffering from respiratory failure. In order to study the effects of CRH
      on sleep EEG and respiratory parameters during sleep, 14 healthy male volunteers
      were investigated in a single-blind placebo controlled design. After an
      adaptation night, polysomnography was performed during two successive nights
      between 23.00 hrs. and 7.00 hrs. During one night placebo was applied, on the
      other 50 micrograms ovine CRH was administered intravenously as a bolus every
      hour from 0.00 hrs. to 6.00 hrs. For the assessment of respiration, blood oxygen
      saturation and thoracic wall movements were measured, as well as nasal and oral
      airflow using the thermistor method. Sleep efficiency parameters and subjective
      perception of sleep quality were not affected following CRH. The following
      alterations were found regarding sleep architecture: REM sleep as well as slow
      wave sleep showed a tendency to decrease under CRH, whereas light sleep tended to
      increase. After an injection of CRH a stimulation of respiration could be
      observed, with an increase of tidal volume over a time interval of a few minutes.
      Blood oxygen saturation was only slightly increased. Cortisol and ACTH
      concentrations were found to be constantly elevated. These results indicate that
      respiration during sleep is clearly affected by CRH with only slight alterations
      of global sleep parameters. No association was found between stimulation of
      ventilation and the occurrence of arousals; the respiratory analeptic effect of
      CRH thus appears to be specific.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584530
TI  - Experience in the long-term treatment of patients with hirsutism and/or acne with
      cyproterone acetate-containing preparations: efficacy, metabolic and endocrine
      effects.
AB  - The effects and side effects of long-term treatment with cyproterone acetate
      (CPA) are described. Hammerstein's reverse sequential regimen (10 days 100 mg
      CPA, 21 days 50 micrograms ethinylestradiol (EE)) was used in most cases,
      although postmenopausal and hysterectomized women received 50 mg CPA/day
      continuously as monotherapy. The degree of androgenization was assessed in 143 of
      a total group of 188 women treated from 1968 to the present. The results of the
      treatment were good or very good in about 75% of hirsutism patients and in more
      than 90% of acne patients. Adverse events were recorded in 23% of cases. Most
      were mild and transient, and caused discontinuation of the therapy in only 9% of
      patients. From this population representing all cases treated and analysed
      retrospectively, a subgroup of patients was selected for a prospective
      investigation. Thirty-five patients with good response to CPA and longlasting
      therapy were included into this 2-year follow-up study; of these, 24 had
      previously received CPA for 5 or more years, 9 for more than 10 years and 2 for
      more than 15 years. Treatment in these patients consisted of 5 different regimens
      of various doses of CPA combined with EE and CPA alone in order to evaluate
      possible effects of concomitant estrogen treatment as well as a possible dose- or
      time-dependency of potential side effects. Clinicochemical, metabolic and
      endocrine parameters were determined at the start and end of the study. The
      hematological and clinicochemical parameters were within the normal ranges. There
      was a slight decrease of glucose tolerance and a moderate increase of insulin and
      C peptide after oral glucose loading. The effects of CPA and EE on lipometabolism
      were slight and apparently dependent on the dose of CPA and the therapeutic
      regimen. No suppression of adrenal function or of responsiveness to ACTH was
      seen. Fasting prolactin levels and serum prolactin concentrations after
      provocation with metoclopramide did not show any gross deviations. Sonography of
      the breast and liver did not show any abnormalities apart from adenofibrosis or
      mastopathy in 2 patients. In conclusion, CPA with or without EE was in our hands
      an effective and safe method of long-term treatment of hirsutism and/or acne in
      women.

PMID- 7584531
TI  - Identification of macroprolactin in a patient with asymptomatic
      hyperprolactinemia as a stable PRL-IgG complex.
AB  - We characterize the molecular form of PRL in a female patient with asymptomatic,
      idiopathic hyperprolactinemia. Size exclusion chromatography revealed that PRL
      was present exclusively in the form of macroprolactin (> 200 kD mol wt). By
      immunoaffinity purification, Western blot analysis, and binding studies the
      molecule was identified as a PRL-IgG complex of extremely high stability.
      Sequence analysis revealed no mutations in the protein coding region of the hPRL
      gene using hPRL cDNA amplified from the patient's peripheral blood lymphocytes.
      In spite of full bioactivity in vitro, as determined by Nb2 bioassay, the complex
      apparently lacks bioactivity in vivo. Its high molecular weight may reduce its
      access to target organs in the periphery as well as centrally.

PMID- 7584532
TI  - Long-term adherence to intensified conventional insulin therapy.
AB  - All diabetic patients of the outpatient clinic of the University of
      Frankfurt/Main, who started intensified conventional insulin therapy (ICT)
      between 1980 and 1991, and who could be followed for at least one year (n = 141)
      were evaluated retrospectively. Fourteen patients changed from ICT to continuous
      subcutaneous insulin infusion (CSII). No patient changed back permanently to
      conventional insulin therapy. Mean glycosylated hemoglobin-levels (HbA1)
      decreased significantly in the first year from 9.3% to 8.5% and remained at a
      near normal level in the following years. HbA1-levels were found not to be
      associated with age, age at diagnosis, weight gain, frequency of visits to the
      outpatient clinic, number of consultations with the dietician as well as the
      frequency of attendance at special seminars for ICT. These results demonstrate
      that ICT lowered blood glucose levels permanently, that patients were highly
      compliant, and that ICT was practicable and safe for long-term treatment under
      routine conditions without initial hospitalization and with an acceptable
      expenditure of time for patients and medical staff.

PMID- 7584535
TI  - Effect of FSH on progesterone secretion by porcine large and small luteal cells
      isolated from early-developing corpora lutea.
AB  - Isolated porcine luteal cells from d 0-3 of the estrous cycle (estrus-d 0) were
      incubated with or without addition of 0, 10, 10(2) or 10(3) ng FSH/ml.
      Progesterone (P4) content was determined after 24 hrs of incubation. In
      nonstimulated conditions the basal P4 production of large cells (LCs) was 65 fold
      higher than that of small cells (SCs). The LCs but not SCs were stimulated by
      doses of 10 and 10(2) ng FSH. FSH in doses of 10 and 10(2) ng did not influence
      P4 production by SCs, but higher doses (10(3) ng) significantly decreased their
      P4 secretion The results indicated that FSH can have a distinct cellular
      luteotropic effect during the early development luteal phase of the pig. FSH
      influenced P4 secretion by LCs whereas, with SCs it had no effect (10 and 10(2)
      ng) or P4 secretion decreased (10(3) ng).

PMID- 7584533
TI  - Glibenclamide stimulates growth of human chondrocytes by IGF I dependent
      mechanisms.
AB  - In rats and men the sulfonylurea glibenclamide augmented skeletal growth.
      However, with the design of the in vivo studies it was not possible to
      distinguish whether the growth promoting effect of glibenclamide was mediated by
      the augmented peripheral insulin or IGF-I levels or if the sulfonylurea had a
      direct effect on chondrocytes. We therefore measured clonal growth of isolated
      human chondrocytes in response to glibenclamide in vitro. Cells were isolated
      from human nose septal cartilage and incubated in a semi-solid medium. Colony
      formation in response to glibenclamide and IGF-I was determined. Glibenclamide
      stimulated clonal growth of chondrocytes in a bell-shaped fashion (p < 0.001). 50
      ng/ml glibenclamide as the maximal dose augmented colony formation to 144 +/- 9%
      compared to clonal growth without glibenclamide in the incubation medium, which
      was designated as 100%. Basal values were obtained with 200 ng/ml glibenclamide.
      Insulin-like growth factor-I (IGF-I) at 3 ng/ml (118 +/- 4%) and 25 ng/ml (149 +/
      8%, p < 0.02) stimulated growth of chondrocytes. To elucidate the possible
      mechanism of glibenclamide on clonal growth, chondrocytes were incubated with the
      sulfonylurea and the IGF-I receptor antibody alpha IR-3. The antibody completely
      abolished the effect of glibenclamide on colony formation. The results suggest
      that the growth promoting effect of glibenclamide on isolated human chondrocytes
      is mediated by IGF-I dependent mechanisms.

PMID- 7584537
TI  - [Life review: promoting the developmental potentials in aging].
AB  - In this paper the theoretical background and practical applications of the life
      review are discussed. Particular emphasis is placed on the relevance of the life
      review for the mastery of developmental transitions across the entire life span
      as well as for adaptation to the challenges commonly associated with aging. The
      terms guided autobiography, life review and reminiscence are explained as are
      techniques for guiding reminiscence and life review. The life review is presented
      as a method which can be effectively used in community or institutional settings.

PMID- 7584534
TI  - Effect of injectable bromocriptine in patients with Cushing's disease.
AB  - The therapeutic efficacy of sustained dopaminergic stimulation in Cushing's
      disease (CD), was investigated performing a three-month trial with monthly 50-100
      mg injections of a bromocriptine depot preparation (Parlodel LAR, Sandoz) in six
      patients with CD. Dopaminergic treatment did not consistently influence pituitary
      adrenal activity, as judged by plasma ACTH, cortisol and urinary free cortisol
      levels as well as by clinical findings. Interestingly, treatment with
      bromocriptine was associated with reappearance of menses in the three patients
      who were amenorrheic. In the five patients submitted to inferior petrosal sinus
      sampling, a parallelism between ACTH and PRL concentrations could be observed
      with a PRL rise, ipsilateral to that of ACTH, ensuing in three patients after
      administration of corticotropin-releasing hormone. In one patient a 55% reduction
      in the size of the pituitary adenoma was demonstrated by MRI carried out at the
      end of treatment. Our findings lead to the following conclusions: a)
      administration of depot injections of bromocriptine to patients with CD appears
      unable to correct hypercortisolism, although it can induce restoration of menses
      in amenorrheic patients; b) enhanced PRL concentrations at the pituitary level
      are probably involved in the amenorrhea often accompanying Cushing's disease.

PMID- 7584538
TI  - [The hospice idea--a new ars moriendi?].
AB  - The concept of hospices, which aim it is to improve the quality of life of dying
      people, so that the possibility of a spiritual and mental development is given
      until their death, finds more and more supporters worldwide. It refers to the
      diaconian attitude of the Middle Ages. As it is open to the religious aspects of
      death, there is a relation to the literature of ars moriendi of the late Middle
      Ages.

PMID- 7584539
TI  - [Terminal care--a burden for professional and familial caregivers?].
AB  - Within a framework of the results of thanatological research the main concerns of
      caring for the dying are worked out. It is shown that the personal besides
      education and training on the job needs a sort of permanent supervision in that
      field of work. Nevertheless caring for the dying will be a burden as long as the
      society neglects and ignores the needs of dying people. This is also true for the
      members of the family, friends and other nonprofessional people, who engage
      themselves in the care for the dying.

PMID- 7584540
TI  - [Support in dying: orientation of expectations and needs of dying patients].
AB  - Experience and behavior of dying people are on a lot of variables. Age, cultural
      background, human relations, personality and environment are some of these
      determinants. For an appropriate care for the dying it is necessary to perceive
      and realize the expectations and requirements of the dying person. The human
      relationships get an important role. Barton (1977) developed a complete
      conception. Accompanying a dying person in a nursing home for the old demands an
      answer on many organizational questions.

PMID- 7584541
TI  - [Experiences from terminal care. Anthropological principles in human practice].
AB  - Paper gives the personal account by physiotherapist working in hospitals and
      geriatric care centers compelled to give moral assistance to old people engaged
      in the process of dying without being prepared for it. Moral assistance ad hoc is
      necessitated by compassion and by patient's struggle to come to terms with an
      extreme situation. To grasp the real meaning of some main topics of philosophical
      and theological anthropology is advocated here as a means to prepare assisting
      person effectively and practically for this task. Topics discussed are: Personal
      presence of a human being, the human soul, vital activity vs. higher life;
      experiences of good and evil in one's life time; success and loss in terms of
      social values; human dignity.

PMID- 7584543
TI  - [Assisted dying--death on demand: borderline between medicine and law].
AB  - In medicine and law the ethical values confront one another: "death with dignity"
      ("allowing to die") versus the "right to life" ("preservation of life"). An
      individual's right to self-determination conflicts with the physician's
      obligation to preserve life. The problematic is discussed from the standpoints of
      both medicine and law, and current developments in the medical profession and
      legal practice are presented.

PMID- 7584542
TI  - [Patients in the terminal phase and their caregivers as a "dyad": how do they
      perceive the finite stage of life, how do they cope with it?--Results of a
      longitudinal study].
AB  - 50 patients in the terminal phase who were treated at home by medical doctors,
      and their caregivers (one caregiver a family) were interviewed up to six times in
      a longitudinal study. Additionally, scales for assessing degree of independence
      in daily living, intensity of pain, and engagement in intra- and extrafamilial
      relationships were used. --Interindividual differences in perceiving (own)
      finitude and in coping with it were high in the group of patients and caregivers.
      Moreover, patients' and caregivers' forms of perceiving and coping with finitude
      were related. These relations point to the necessity of a "dyadic" perspective in
      analyzing patterns of perceiving and coping with finitude. --In the group of
      patients, perceiving own finitude and coping with it was also related to
      intensity of pain, degree of independence in daily life, degree of perceived
      social integration, and to the feeling of being needed. Results of our study do
      not confirm the assumption that there is a characteristic pattern of perceiving
      and coping with finitude in terminally ill patients and their caregivers.

PMID- 7584536
TI  - [Assisted dying and death on demand].

PMID- 7584544
TI  - [Euthanasia as legally liable homicide or sanctioned assisted suicide].
AB  - Euthanasia is as culpable homicide guilty (murder), counselling or aiding suicide
      however not. The patient has the right to take own decisions concerning the
      treatment which could unduly prolong the death process.

PMID- 7584545
TI  - [Aging and dying--reflections on statistical figures].
AB  - Aging and death of man have changed decisively during the last centuries. Today,
      three age-dependent mortalities can be distinguished: the mortalities in the
      early years of life, those caused by external forces, and the rest of mortality.
      The logarithm of the rest of mortality is, starting with the 20th year of life,
      relatively strictly correlated to age. Only this age-dependent mortality can be
      regarded as a "natural" mortality. It is however enabled only by a culturally and
      technically extremely favorable environment. The slope of the age-dependent
      mortality is relatively stable geographically and in the course of time, and is
      nearly equal for both sexes. Of various diseases, their relative mortalities
      (expressed in percent of total mortality) indicates an age-specific
      susceptibility for the causes of death, with high percentages either in youth, in
      midlife or in high age. The mortality of all cancers was relatively stable during
      the last decades, whereas the specific mortalities of different cancer sites
      varied to a much higher degree ("vicarious mortality"). Death is programmed
      relatively rigidly, as far as it is not related to violence (accidents,
      poisoning, murder). Perhaps the genetical determination is prevailing. The slope
      of the programmed part of mortality of woman changes in its steepness after the
      age of 60, with an increasing rate of mortality.

PMID- 7584546
TI  - [Geriatric assessment--case finding by screening hospitalized patients].
AB  - The effectiveness of geriatric assessment depends on patient selection. A simple
      screening procedure should facilitate the detection of appropriate patients by
      recording functional impairments and geriatric risks. We studied the feasibility
      of, and the information from the screening, and the recommendations of
      assessments derived from the screening. The screening revealed an average of five
      findings in 245 of 247 patients consecutively admitted. The most frequent
      problems were impaired activities of daily living and mobility, and impaired
      memory. Geriatric assessment was recommended to 44% of newly hospitalized
      patients. These patients were older, with more of them living at home and alone,
      and nearly half of them had five or more findings in the screening with chronic
      problems being predominant. The screening procedure is feasible. It appears
      useful and reasonable to select patients for geriatric assessment while they are
      in hospital.

PMID- 7584548
TI  - Vasoactive intestinal polypeptide and nitric oxide synthase distribution in the
      enteric plexuses of the human colon: an histochemical study and quantitative
      analysis.
AB  - Vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS) positive
      innervation patterns were immunohistochemically and statistically evaluated in
      the human colon. Specimens from the right colon (cecum, ascending and right
      transverse colon) and left colon (left transverse and descending colon) were
      obtained surgically, fixed either in paraformaldehyde or in Carnoy's or in
      Bouin's and paraffin embedded. Sections were stained with hematoxylin-eosin,
      toluidine blue, cresyl violet, neuron-specific enolase, anti-VIP, and anti-NOS.
      The same results were obtained regardless of the fixative used. Enolase-positive,
      VIP-positive, and NOS-positive cells were occasionally found within the circular
      muscle and interpreted as neurons. VIP-positive nerve fibers were evenly
      distributed within the circular muscle while NOS-positive ones were lacking in
      its inner portion. The left colon was richer in neurons than the right colon, at
      both plexuses. VIP- and NOS-positive neuron densities were higher at the left
      than at the right colon, whereas at all colonic levels VIP-positive neuron
      percentages at both plexuses and NOS-positive ones at the myenteric plexus were
      similar. At the submucous plexus the NOS-positive neuron percentage was lower
      than that of the VIP-positive one. IN CONCLUSION: (a) the right colon contains a
      lower number of neurons and of VIP- and NOS-positive ones than the left colon,
      and (b) VIP- and NOS-positive fibers are differently distributed in the inner and
      outer portions of the circular muscle.

PMID- 7584550
TI  - Lectin histochemistry of lipofuscin and certain ceroid pigments.
AB  - Little is known at present about the saccharide components of lipofuscin (age
      pigment) and ceroid pigments in situ. The purpose of this study was, therefore,
      to study in detail the lectin reactivities of lipofuscin in neurons and cardiac
      myocytes of old humans and rats. In addition, those of diverse ceroid pigments
      found in human aortic atheromas, in the livers of choline-deficient rats, in the
      uteri of vitamin E-deficient rats and in the crushed epididymal fat pad of rats,
      are included. Cryostat and deparaffinized sections from all these tissues were
      either extracted with a solvent mixture of chloroform-methanol-water (10:10:3,
      v/v) and incubated with 7 different biotinylated lectins or left untreated.
      Delipidation was done in order to study whether it was possible to discriminate
      between the saccharide moieties of glycolipids and glycoproteins of lipofuscin
      and ceroid pigments in situ. Other similarly treated sections were used to study
      the autofluorescence, sudanophilia, acid-fastness and reactivity to PAS. The
      frequency and intensity of lectin binding and standard histochemical properties
      of all the pigments were evaluated semi-quantitatively and blind. The results
      indicated that mannose was in general the most consistently detected sugar
      residue in lipofuscin granules of humans and rats, and that this pigment may also
      contain acetylglucosamine, acetylgalactosamine, sialic acid, galactose and
      fucose. However, notable differences were found not only in the lipofuscin
      saccharide components of different cell types of humans and rats, but also in
      those in the same type of cells in both species. Although mannose was not
      detected in the hepatic ceroid of choline-deficient rats, this saccharide moiety
      was almost always present in the other ceroid pigments. Each of the ceroids also
      contained other types of saccharides although the frequency of the latter varied
      between different ceroid pigments. While lipofuscin and each of the ceroid
      pigments showed somewhat different lectin binding patterns, the variability in
      the frequency of reactivity to lectins suggests that these patterns may not be
      permanent but transient. In this sense, it appears that lectin histochemistry may
      not allow these pigments to be differentiated. Furthermore, the extractive
      procedures used in this study did not enable us to determine whether the
      saccharides detected in the pigments in situ corresponded to glycolipids or
      glycoproteins.

PMID- 7584547
TI  - Microwave irradiation improvements in the silver staining of the nucleolar
      organizer (Ag-NOR) technique.
AB  - The well-known technique of silver staining of the nucleolar organizer (Ag-NOR)
      is improved in contrast, selectivity and speed when performed with microwave
      irradiation. The Ag-NOR technique is a very useful tool for studies on the
      functional morphology and molecular architecture of the nucleolus, and is reputed
      to be one of the best techniques for diagnosis and prognosis of cancer lesions.
      To test the generality of the enhancing effects, our study has involved the use
      of both mammalian and plant cells. Two steps in the process are improved
      quantitatively by microwave irradiation: fixation and staining itself. Fixation
      with the ethanol-based reagent, Kryofix, for 3 min in the microwave oven,
      resulted in good structural preservation at the optical level, and enhanced the
      contrast and selectivity of silver staining. On the contrary, we found that
      neither glutaraldehyde fixation, nor a treatment of sections with Carnoy's
      solution, improved Ag-NOR staining. After an analysis of the effects of the
      different substances involved in sample preparation, we conclude that ethanol is
      an essential factor for fixation for nucleolar staining, particularly if
      aldehydes are eliminated from fixative solutions. The process of staining was
      performed with a drop of staining solution on a semithin section of plastic
      embedded tissue in the microwave oven for 1 min. Staining under these conditions
      always improved the visualization of nucleoli, regardless of the fixation
      procedure. Therefore, microwave irradiation at both steps is recommended for
      giving the best results. Microwave irradiation probably enhances fixation by
      controlled heat, whereas the increase in reactivity of the staining solution is a
      direct effect by the microwaves on the silver ions themselves. We used this
      method to study nucleolar materials during mitosis in proliferating plant cells.
      Current applications of Ag-NOR staining can be improved with this technical
      modification.

PMID- 7584552
TI  - Changes in NADPH-diaphorase activity in the rat dorsal horn following an acute
      experimental myositis.
AB  - Previous neurophysiological experiments have shown that in rats with an acute
      myositis of the gastrocnemius-soleus muscle, dorsal horn neurones exhibit an
      increase in responsiveness to peripheral stimulation and in background activity.
      The present study investigated the possible correlation between changes in NADPH
      diaphorase activity and neurophysiological alterations. In the animals used for
      the electrophysiological experiments the diaphorase activity in sections of the
      lumbar spinal cord was determined with the NADPH-nitroblue tetrazolium reaction.
      The main findings was a massive reduction in the number of diaphorase-positive
      cells in the superficial dorsal horn in animals with a myositis. The staining
      intensity in the remaining neurones was unchanged. The results are interpreted as
      indicating that the myositis in addition to the surgical operations represents a
      supramaximal input to the dorsal horn causing neurotoxic effects in diaphorase-
      positive neurones.

PMID- 7584549
TI  - Changes in cytokeratin expression in epidermal keratinocytes during wound
      healing.
AB  - In order to investigate the re-epithelialization process during wound healing,
      the hair on the back of guinea pigs was shaved and then excisional wounds were
      made through the entire thickness of the skin. Histological changes were observed
      and changes in the expression of different cytokeratin polypeptides were examined
      using an immunohistochemical technique. Immunohistochemical study revealed that
      the proliferating and migrating keratinocytes expressed the same cytokeratins as
      the basal cells of normal epidermis. In addition, the entire epidermis of fairly
      remote areas from the edges of the wound where no thickening was observed showed
      a temporarily abnormal staining pattern. The suprabasal cells in the regenerating
      epidermis temporarily expressed cytokeratins not only specific for suprabasal
      cells but also specific for basal cells. The cytokeratins expressed in normal
      basal keratinocytes were also present in the thickened granular layers. These
      data indicate that the expression of cytokeratins in the epidermal keratinocytes
      (even in fairly remote areas from the wound edges) changes during wound healing,
      that the origin of the migrating keratinocytes from the remaining epidermis seems
      to be the basal cells in the epidermis, and that the appearance of keratohyalin
      granules is not related to changes in cytokeratin expression.

PMID- 7584553
TI  - Qualitative and quantitative detection of alkaline phosphatase coupled to an
      oligonucleotide probe for somatostatin mRNA after in situ hybridization using
      unfixed rat brain tissue.
AB  - In situ hybridization (ISH) of somatostatin (SOM) mRNA was carried out on
      sections of rat brain using an alkaline phosphatase (AP) coupled oligonucleotide
      probe. Different hybridization and AP development conditions were tested for
      qualitative and quantitative detection of target mRNA on sections of unfixed
      tissue. Hybridization signal intensities after 24 h of hybridization were high.
      Comparison with adjacent formaldehyde-fixed tissue sections and hybridization for
      various lengths of time (2-42 h) indicated that in unfixed tissue retention of
      SOM mRNA was at least as high as after fixation, and that the mRNA was not
      degraded during hybridization. The use of tetranitroblue instead of nitroblue
      tetrazolium chloride in the AP detection medium provided a superior signal-to
      noise ratio, and medium stability was improved for quantitative studies on
      unfixed sections by adding 10% polyvinyl alcohol at pH 8.5. Microphotometric
      measurements of mean optical densities (MOD) of the formazan reaction product in
      a defined area within individual neurons of the lateral central amygdaloid
      nucleus showed a linear increase over the first 23 h of AP reaction time. The
      mean MOD values per neuron were comparably high in various equally thick sections
      of the nucleus and increased with section thickness in a linear manner. The
      findings indicate that the ISH and detection reagents penetrate the entire
      section and that there is a linear relationship between the amount of AP reaction
      product measured and the amount of mRNA present in the measured area. Thus, ISH
      using an AP-coupled oligonucleotide on sections of unfixed tissue appears
      suitable for quantitative mRNA detection.

PMID- 7584551
TI  - Immunocytochemical evaluation of protein kinase C translocation to the inner
      nuclear matrix in 3T3 mouse fibroblasts after IGF-I treatment.
AB  - The complex pathway which links the agonist-cell membrane receptor binding to the
      response at the genome level involves, among other elements, protein kinase C
      (PKC). Agonists acting at the cell membrane can affect an autonomous nuclear
      polyphosphoinositide signaling system inducing an activation of nuclear
      phosphoinositidase activity and a subsequent translocation of PKC to the nuclear
      region. The fine localization of PKC has been investigated by means of electron
      microscopy quantitative immunogold labeling in 3T3 mouse fibroblasts,
      mitogenically stimulated by IGF-I. The enzyme, which in untreated cells is
      present in the cytoplasm, except for the organelles, and in the nucleoplasm,
      after IGF-I treatment is reduced in the cytoplasm and almost doubled in the
      nucleus. The PKC isoform translocated to the nucleus is the alpha isozyme, which
      is found not only associated with the nuclear envelope but mainly with the
      interchromatin domains. By using in situ matrix preparations, PKC appears to be
      retained at the nuclear matrix level, both at the nuclear lamina and at the inner
      nuclear matrix, suggesting a direct involvement in the phosphorylation of nuclear
      proteins which are responsible for the regulation of DNA replication.

PMID- 7584556
TI  - Nitric oxide synthase in guinea pig sympathetic ganglia: correlation with
      tyrosine hydroxylase and neuropeptides.
AB  - Nitric oxide synthase (NOS) has previously been reported in a small population of
      postganglionic sympathetic neurons in the guinea pig. The present study of
      paravertebral ganglia and the inferior mesenteric ganglion aimed to classify
      these neurons according to their content of neuropeptides (calcitonin gene
      related peptide, neuropeptide Y, vasoactive intestinal peptide) and the rate
      limiting enzyme of catecholamine synthesis, tyrosine hydroxylase, by means of
      immunohistochemical and histochemical double-labelling techniques. NOS-containing
      neurons belonged to the non-catecholaminergic population of postganglionic
      neurons, and partial co-existence was found with neuropeptide Y and vasoactive
      intestinal peptide immunoreactivities but not with calcitonin gene-related
      peptide. However, most of the NOS-containing neurons contained none of the
      neuropeptides, thus representing a hitherto unrecognized population of
      postganglionic neurons. The findings show that NOS is localized to small but
      neurochemically highly specific populations of postganglionic neurons, which most
      likely reflects an association with target- and function-specific pathways.

PMID- 7584555
TI  - Secretoneurin: a new peptide in the human enteric nervous system.
AB  - Secretoneurin is a functional neuropeptide derived from secretogranin II
      (chromogranin C). This proprotein is processed to varying degrees in
      neuroendocrine tissues. In the present study we established by gel filtration
      high performance liquid chromatography that in human intestinal wall and mucosa
      an antiserum against secretoneurin detects as the major immunoreactive moiety the
      free peptide secretoneurin. In the mucosa some larger immunoreactive peptides
      were also present, however, a significant amount of the intact proprotein
      secretogranin II could not be detected. By immunohistochemistry we studied the
      distribution of secretoneurin within the gut. Antibodies to protein gene product
      9.5 and chromogranin A were used to identify all neurons and endocrine cells,
      respectively, whilst those to the peptides substance P, CGRP and somatostatin
      were used for the further characterization of individual secretoneurin-positive
      structures. Secretoneurin immunoreactivity was found in nerve fibres in all
      layers of the gut wall. In both myenteric and submucous plexuses, nerve fibres
      and the majority of ganglion cells were secretoneurin-immunoreactive. In the
      mucosa, some secretoneurin-positive nerve processes ran parallel to the basal
      membrane of epithelial cells, occasionally invading the epithelial layer.
      Secretoneurin immunoreactivity was found in endocrine cells, mostly D cells, in
      the following regions in descending order of density: stomach/duodenum; rectum;
      colon; ileum. Thus, secretoneurin is a new major peptide within the human enteric
      neuroendocrine system. Its presence in abundant myenteric ganglion cells may
      imply a role in the modulation of gastrointestinal motility. The chemotactic
      properties of secretoneurin and its possible localization in sensory fibres
      suggest that this peptide may be involved in the genesis of intestinal
      inflammation.

PMID- 7584554
TI  - Cellular distribution of the aquaporins: a family of water channel proteins.
AB  - A group of transmembrane proteins that are related to the major intrinsic protein
      of lens fibers (MIP26) have been named "aquaporins" to reflect their role as
      water channels. These proteins are located at strategic membrane sites in a
      variety of epithelia, most of which have well-defined physiological functions in
      fluid absorption or secretion. However, some aquaporins have been localized in
      cell types where their role is at present unknown. Most of the aquaporins are
      delivered to the plasma membrane in a non-regulated (constitutive) fashion, but
      AQP2 enters the regulated exocytotic pathway and its membrane expression is
      controlled by the action of the antidiuretic hormone, vasopressin. These pathways
      of constitutive versus regulated delivery to the plasma membrane have been
      reconstituted in transfected LLC-PK1 epithelial cells, indicating that the
      information encoded within the protein sequence is sufficient to allow sorting of
      newly synthesized protein into distinct intracellular vesicles. Finally,
      different members of the aquaporin family can be targeted to apical, basolateral
      or both apical and basolateral plasma membrane domains of polarized epithelial
      cells. This implies that signals for the polarized targeting of these proteins
      also is located in non-homologous regions of these similar proteins. Thus, future
      investigations on the aquaporin family of proteins will provide important
      information not only on the physiology of membrane transport processes in many
      cell types, but also on the targeting and trafficking signals that allow proteins
      to enter distinct intracellular vesicular pathways in epithelial cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584557
TI  - The effect of sodium tetrathionate stabilization on the distribution of three
      nuclear matrix proteins in human K562 erythroleukemia cells.
AB  - Using both conventional fluorescence and confocal laser scanning microscopy we
      have investigated whether or not stabilization of isolated human erythroleukemic
      nuclei with sodium tetrathionate can maintain in the nuclear matrix the same
      spatial distribution of three polypeptides (M(r) 160 kDa and 125 kDa, previously
      shown to be components of the internal nuclear matrix plus the 180-kDa nucleolar
      isoform of DNA topoisomerase II) as seen in permeabilized cells. The incubation
      of isolated nuclei in the presence of 2 mM sodium tetrathionate was performed at
      0 degrees C or 37 degrees C. The matrix fraction retained 20-40% of nuclear
      protein, depending on the temperature at which the chemical stabilization was
      executed. Western blot analysis revealed that the proteins studied were
      completely retained in the high-salt resistant matrix. Indirect
      immunofluorescence experiments showed that the distribution of the three antigens
      in the final matrix closely resembled that detected in permeabilized cells,
      particularly when the stabilization was performed at 37 degrees C. This
      conclusion was also strengthened by analysis of cells, isolated nuclei and the
      nuclear matrix by means of confocal laser scanning microscopy. We conclude that
      sodium tetrathionate stabilization of isolated nuclei does not alter the spatial
      distribution of some nuclear matrix proteins.

PMID- 7584560
TI  - Immunocytochemical localization of L-alpha-hydroxyacid oxidase in dense bar of
      dumb-bell-shaped peroxisomes of monkey kidney.
AB  - Localization of the B of L-alpha hydroxyacid oxidase (HOX-B) in monkey kidney
      peroxisomes was investigated by immunoelectron microscopic techniques. Kidneys of
      Japanese monkeys, Macaca fuscata, were fixed with 4% paraformaldehyde + 0.25%
      glutaraldehyde and embedded in LR White resin. Thin sections were stained for HOX
      B and catalase by the immunogold technique. HOX-B was localized in the marginal
      plates of normal peroxisomes and the dense bar of dumb-bell-shaped peroxisomes.
      Catalase was detected in the matrix of normal peroxisomes and in the terminal
      dilatations of dumb-bell-shaped peroxisomes. There were no gold particles
      indicating presence of catalase associated with the marginal plates or with the
      dense bars. Immunoblot analysis of monkey kidney homogenate showed that HOX-B has
      a molecular mass of 42 kDa that was slightly larger than that of rat kidney HOX-B
      (39 kDa). The results show that the dense bar of dumb-bell-shaped peroxisomes in
      monkey kidney is composed of at least HOX-B and is a variation of the marginal
      plates.

PMID- 7584559
TI  - Muscle-specific enzyme activity patterns of the capillary bed of human oro
      facial, masticatory and limb muscles.
AB  - Enzyme-histochemical methods were used to analyse the activities of alkaline
      phosphatase (AP), dipeptidylpeptidase IV (DPP IV) and adenosine triphosphatase
      (ATPase) in capillaries of four different human oro-facial muscles, the major and
      minor zygomatic, the orbicularis oris and buccinator, one masticatory, the
      masseter and two limb muscles, the biceps brachii and first dorsal interosseus
      muscles. In all muscles, except for the orbicularis oris, the majority of the
      capillaries lacked enzyme activity. Therefore, none of these enzymes seems to be
      reliable as a general marker for human muscle capillaries. In general, the
      capillaries of the limb muscles and the major and minor zygomatic and the
      buccinator, were similar in their staining pattern for AP and ATPase, but
      differed in DPP IV staining. The orbicularis oris muscle differed from the other
      muscles by showing the largest proportion of capillaries with AP and ATPase
      activity. The masseter muscle had the largest proportion of capillaries stained
      for DPP IV. The muscle specific differences in enzyme activity of the capillaries
      are in agreement with our previous findings of specific differences between limb,
      oro-facial and masticatory muscles with respect to capillary supply and
      composition of fibre types and myosins. The results reflect functional
      specialization of the capillary bed of human muscles.

PMID- 7584558
TI  - Changes in the ultrastructural distribution of prolactin and growth hormone mRNAs
      in pituitary cells of female rats after estrogen and bromocriptine treatment,
      studied using in situ hybridization with biotinylated oligonucleotide probes.
AB  - The expression and distribution of prolactin (PRL) mRNA and their alterations
      induced by estrogen and bromocriptine were investigated using non-radioisotopic
      in situ hybridization (ISH) at the electron microscopic (EM) level. Our EM-ISH
      studies using biotinylated oligonucleotide probes showed that estrogen induced
      whirling changes of the rough endoplasmic reticulum (RER) of female rat PRL cells
      and increased transcription of PRL genes located on the polysomes of the whirling
      RER. The presence of mammosomatotroph cells in the rat pituitary gland was also
      verified in our EM-ISH studies. After bromocriptine administration, PRL cells
      contained many secretory granules due to the inhibition of secretion. Pre- and
      post-embedding EM-ISH and northern hybridization studies revealed that
      bromocriptine induced the distorted, vesiculated, and dilated RER, and also the
      suppressed PRL mRNA expression. The activity of protein kinase C (PKC), which
      mediates PRL gene expression, tended to be elevated by estrogen and suppressed by
      bromocriptine. Therefore, it is considered that the ultrastructural and
      quantitative changes in PRL mRNA expression evoked by estrogen and bromocriptine
      may be mediated by the intracellular signal transduction system, including PKC.

PMID- 7584561
TI  - Catecholamine-synthesizing enzymes in the rat stomach.
AB  - Local production of catecholamines in the stomach of the rat was studied by
      immunohistochemical demonstration of tyrosine hydroxylase (TH), dopamine-beta
      hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT), the enzymes
      catalyzing the formation of dopamine, noradrenaline and adrenaline, respectively.
      A rich innervation of TH- and DBH-immunoreactive nerve fibers was seen in the
      muscular layers and the myenteric plexus, in the submucosa and in the walls of
      submucosal blood vessels and in the lamina propria at the base of the epithelial
      layer. In addition, TH-, but not DBH-immunoreactive nerve fiber networks
      surrounding ganglion cells in the myenteric plexus were frequently observed,
      indicating dopaminergic preganglionic innervation of the myenteric plexus. In the
      oxyntic epithelium, single TH- and DBH-immunoreactive fibers extended in the
      strands of lamina propria as far as the middle portion of the gastric glands. A
      small population of single angulate cells in the oxyntic epithelium showed TH-,
      but not DBH-immunoreactivity. No specific PNMT immunoreactivity was observed.

PMID- 7584564
TI  - [Obstetric complications and medical and surgical complication: intensive care
      and management. A symposium summary].

PMID- 7584563
TI  - Fluorescence of the natural dye saffron: selective reaction with eosinophil
      leucocyte granules.
AB  - Treatment of methanol-fixed chicken, rat, horse and human blood smears with
      saturated solutions of saffron in borate buffer at pH 10 results in a bright
      yellow-green fluorescence reaction of the acidophilic cytoplasm granules in
      mammalian eosinophils and chicken heterophils under violet-blue exciting light.
      Spectral characteristics of saffron (emission peak at 543 nm under 436 nm
      excitation) and its selective fluorescence with acidophilic structures support
      the possibility of employing this old microscopic stain as a new fluorochrome.

PMID- 7584562
TI  - Fluorescence of eosinophil leucocyte granules induced by 1-hydroxy-3,6,8
      pyrenetrisulfonate. Visualization of differences in protein isoelectric points.
AB  - After treatment of horse, rat and human blood smears with alkaline solutions of 1
      hydroxy-3,6,8-pyrenetrisulfonate (HPTS), eosinophil leucocyte granules were the
      unique cell components which showed a bright green fluorescence. When stained
      with HPTS at pH 10, the whole granule of horse eosinophils showed high emission
      which strongly diminished after washing or staining in salt solutions or by using
      blocking methods for amino groups. Using HPTS at pH 12, the fluorescence reaction
      of horse granules was specifically located in the peripheral region, appearing as
      fluorescent rings. These microscopic observations, which indicate differences in
      the isoelectric point of proteins within the eosinophil granule, were also
      confirmed by HPTS staining of protein blots as model substrates. Spectral
      analysis of HPTS at pH 10 and 12 showed practically identical absorption and
      emission spectra with peaks at 450 nm and 510 nm, respectively. Our results
      indicate that mainly ionic binding occurs between cationic proteins and HPTS in
      alkaline solution, and that the most cationic proteins (with isoelectric points
      at pH higher than 12) are located in the peripheral annular region of horse
      eosinophil granules.

PMID- 7584565
TI  - [Clinical use of selective reduction in multifetal pregnancies].
AB  - Selective reduction under ultrasound guidance was carried out in 12 multifetal
      pregnancies with over 3 fetuses during 8 to 14 gestational weeks. It was
      performed transabdominally in 9 women but in other 3, tansvaginal approach was
      used. Ten women have already delivered 19 viable infants, but the remaining 2
      aborted after amniotic rupture during the second trimester. Selective reduction
      is a safe, feasible method for management of multifetal pregnancies with over 3
      fetuses.

PMID- 7584566
TI  - [Lipid peroxidation in plasma and the activity of superoxide dismutase (SOD) in
      pregnant women with premature rupture of membrane].
AB  - To investigate the condition of lipid peroxidation and antioxidation in premature
      rupture of membrane (PROM), we selected 50 women with PROM, without significant
      inducing factors, as study group, and 116 healthy and uneventful gestational age
      pregnant women as controls. Blood samples were collected from the maternal and
      umbilical cord vein. The concentration of plasma malondialdehyde (MDA) and the
      activity of erythrocyte superoxide dismutase (SOD), selenium glutathione
      peroxidase (SeGSH-Px) were determined. The results showed that the plasma
      concentrations of MDA in the maternal and umbilical cord vein were significantly
      higher in the PROM group than in the control group (P < 0.01), and the activity
      of erythrocyte SOD and SeGSH-Px were significantly lower in the PROM group than
      in the control group (P < 0.01). The levels in plasma of MDA and SeGSH-Px in
      erythrocyte were significantly higher in the maternal blood than in the umbilical
      cord blood, but the SOD activity was significantly lower. A positive correlation
      of MDA concentration in plasma was found both in the maternal and umbilical cord
      veins (P < 0.01). It is suggested that lipid peroxidation improved may be one of
      the factors of PROM induced, and one of the factors of other related diseases
      induced by PROM.

PMID- 7584567
TI  - [Changes of proto-oncogene expression and cytosolic free calcium in activited T
      lymphocytes of aged mice].
AB  - Dot blot showed that the expression of proto-oncogene c-fos was inhibited in
      lymphocytes from old mice (20-24 months). In order to measure the effect of aging
      on signal transduction, we separated T cells by passage of spleen lymphocytes
      through long nylon fiber columns. Con A-induced [3H] TdR incorperation in cells
      from old mice was lower than that from young mice (2 months). The maximum level
      of [3H]TdR incorperation of old mouse T cells was only 22% of that of young mouse
      T cells. When T cells were stimulated with the combination of a phorber ester
      (PMA) and a calcium ionophore (ionomycin), [3H]TdR incorperation remained
      depressed in old mouse T cells. Further, cytosolic free calcium level was
      measured by monitoring fluoresence intensity in fura-2/AM loaded T cells. At 10
      minutes after con A stimulation, the concentration of cytosolic free calcium
      ([Ca2+]) in old mouse T cells elevated to 273 x 10(-9)mol/L, while [Ca2+] in
      young mouse T cells markedly increased to 637 x 10(-9)mol/L. When T cells were
      stimulated with the combination of PMA and ionomycin, at 7 minutes, [Ca2+] in old
      mouse T cells elevated to 790 x 10(-9)mol/L, while [Ca2+] in young mouse T cells
      markedly increased up to 2190 x 10(-9)mol/L.

PMID- 7584568
TI  - [Effect of electric fields on the proteins in nerve regeneration conditioned
      fluid].
AB  - 80 SD rats were randomly divided into four groups of 20 each: local
      electrostimulation of nerve stump (Group LS); electro-stimulation of myeloneure
      (Group N); electrostimulation of the denervated muscle (Group M); and controls
      (Group C). The left lateral sciatic nerve of rats was excised 5mm in length, and
      the severed nerve was bridged with the silicon tube. The gap between the stumps
      was about 10mm. At 3rd, 7th, 14th, 21st and 28th day after nerve transection and
      tube implantation, the fluid in the silicon tube was aspirated. The sample of
      fluid was spun and 4 microliters aliquots were taken from the supernatant. Then
      the electrophoresis of the aliquots was made by phase-system and assayed to the
      amount and variety by Gel Scan system. The results showed that the group LS had a
      high increase in the protein amount than others in the range of 6.16-10.23 x
      10(3)D molecular weight. We believe that it is one of the mechanisms of the
      electric fields promoting nerve regeneration.

PMID- 7584569
TI  - [Quantitative study of myocardial mitochondrial DNA4977 deletion in rheumatic
      heart disease and its significance].
AB  - To better understand the mechaenisms of cardiac function damaged by chronic
      hypoxemia in rheumatic heart disease, we investigated the level of the 4977 base
      pair mitochondrial DNA (mtDNA4977) deletion in 16 patients with rheumatic heart
      disease (RHD) by using polymerase chain reaction (PCR). Myocardial
      malondialdehyde (SOD) activity was also measured. In control group, mtDNA4977
      deletion appeared after 45 years old and reached a maximum of 0.0042%. A higher
      level of mtDNA4977 deletion (0.02%-1.26%) was found in RHD group. Because
      mtDNA4977 deletion removes 8 genes coding for subunits of complexes of
      respiratory chain, its deletion can inhibit oxidative phosphorylation, reduce ATP
      production and hinder the recovery of cardiac function. In addition, myocardial
      MDA content increased and SOD activity decreased in the RHD group as compared
      with the control group. This indicates that the generation of oxygen free
      radicals enhances and the elimination of free radicals reduces. Oxygen free
      radical can be an important factor in myocardial mitochondrial DNA injury and
      lead to mitochondrial DNA deletion.

PMID- 7584571
TI  - [Expression of endothelin-1 mRNA, endothelin receptor-A and nitric oxide synthase
      mRNA in pulmonary artery and right ventriculus cordis of rats exposed to
      hypoxia].
AB  - Endothelins (ETs) are a family of novel regulatory peptides which can constrict
      the vascular and promote the proliferation of vascular smooth muscle cells. Serum
      ET-1 was elevated, and nitric oxide (NO) levels were reduced in hypoxic pulmonary
      hypertension. However, the exact mechanism remains unclear, and no study has
      elucidated if hypoxia could stimulate directly overgrowth of right ventricle in
      patients with chronic cor pulmonale. To investigate the role of ET-1 and NO in
      hypoxia-induced pulmonary hypertension and right ventricular hypertrophy, we
      measured the levels of ET-1 mRNA, ET receptor-A (ETR-A) mRNA and nitric oxide
      synthase (NOS) mRNA in the pulmonary artery and right ventricle of rats exposed
      to hypoxia (FiO = 0.1, 8 hours daily for 1, 2 and 3 weeks) by reverse
      transcription-polymerase chain reaction (RT-PCR). ET-1 mRNA level of pulmonary
      artery raised after 1 week's hypoxia (P < 0.05), and after 2 weeks' hypoxia, it
      returned to near normal, but elevated significantly again after 3 weeks' hypoxia.
      Pulmonary artery ETR-A mRNA in 1 and 2 weeks hypoxic groups showed no significant
      change, but it raised significantly in 3 weeks' hypoxic group. After exposure to
      hypoxia for 1, 2 and 3 weeks, NOS mRNA in the pulmonary artery all reduced
      significantly (P < 0.05). The right ventriculus cordis showed a significant
      increase in weight after 3 and 2 weeks' hypoxia. ET-1 mRNA showed no significant
      change but ETR-A mRNA increased significantly after 2 weeks' hypoxia; both ET-1
      mRNA and ETR-A mRNA showed significant increase in weight after 3 and 2 weeks'
      hypoxia. In the ventriculus cordis of rats exposed to hypoxia for 2 and 3 weeks,
      NOS mRNA had no significant change.

PMID- 7584570
TI  - [Changes in cytosolic free calcium and thromboxane B2 synthesis in platelets from
      diabetic subjects].
AB  - Using fura-2, a fluorescence indicator, we evaluated the changes of platelet
      cytosolic free calcium concentration ([Ca2+]i) and its role in regulation of
      thromboxane B2 (TXB2) synthesis in patients with diabetes mellitus (DM group, n =
      27) and in healthy subjects (control group, n = 15). The A23187-evoked elevation
      of [Ca2+]i and TXB2 production were higher in the DM group than in the control
      group (P < 0.01 respectively). The rise in [Ca2+]i was correlated positively with
      TXB2 production. In contrast, stimulation with arachidonic acid, TXB2 production
      was unaltered between the groups, although arachidonate-induced [Ca2+]i was
      higher in the DM group than in the control group (P < 0.05). The results
      suggested that changes in platelets [Ca2+]i in diabetic subjects may contribute
      to increase in TXB2 synthesis, involved libration of free arachidonate from
      membrance phospholipids by the action of phospholipases. Since no significant
      difference was found between the diabetic patients with microangiopathy (n = 13)
      and without microangiopathy (n = 14), the results above may be involved in the
      development of diabetic microangiopathy.

PMID- 7584572
TI  - [Gene diagnosis of adult polycysitic kidney disease--using polymorphic
      microsatellite markers].
AB  - Gene diagnosis of adult polycystic kidney disease (APKD) is possible by genetic
      linkage analysis using linked restriction fragment length polymorphisms (RFLP) on
      both sides of the PKD1. This technique is laborious, expensive and sample- time-
      consuming. SM7 is a polymorphic microsatellite that tightly linked with the PKD1.
      We combined PCR with polyacrylamide gel electrophoresis and method of gel Ag+
      staining to detect the allelus and genotype frequencies of the microsatellite
      amplificated in unrelated Chinese population. The study of 8 APKD families with
      SM7 demonstrated that the technique is quite simple, fast, sensitive and does not
      require the use of radioisotopes and ultraviolet. It could provide a powerful
      method for the presymptomatic and prenatal diagnosis of APKD.

PMID- 7584574
TI  - [Pulmonary function detection in newborn infants].
AB  - We studied 120 full-term newborn infants and 20 pre-term infants by means of
      recording tidal breathing flow volume loops, passive flow volume technique and
      open circuit N2 washout technique. In the preterm infants, ventilatory function,
      FRC and Crs were lower than those in full-term infants, and Rrs were higher than
      those of full-term infants. TV, MV and PTEF were positively corelated with age
      (day), weight and height FRC, Crs and Trs were positively corelated with weight
      and height. TBFV loop in normal newborn infants did not show round or ellipse
      curve. The curve of expiration rose quickly, the position of expiration peak
      closed to the front, and decending line of expiration was relatively tilting. RR,
      Ti/Ttot, VPF, TPF, PF25, PTEF/TV, ME/MI, FRCkg, Crskg, sCrs, Rrs and sRrs were
      valuble indices in neonatal pulmonary function test. The results of our study are
      important in the establishment of normal values of pulmonary function indices for
      newborn infants in China.

PMID- 7584575
TI  - [Variant gap phenomenon in A-V conduction].
AB  - In 361 consecutive patients 4 with variant gap phenomenon (VGP) underwent
      intracardiac electrophysiological studies. The premature atrial response
      initially delayed in His-Purkinje system (HPS) which had a long relative
      refractory period (RRP), and H-V interval was prolonged. However, as atrial
      responses were more premature, the atrioventricular node (AVN) showed RRP and
      slowed down the conduction, that made HPS get rid of RRP before the response
      arriving. Thus the conduction resumed, and H-V interval became normal. It was
      different from the classic gap phenomenon. We call it variant gap phenomenon.

PMID- 7584573
TI  - [Correlative study of erythrocyte membrane insulin receptor with blood lipids and
      albumin in non-obese noninsulin-dependent diabetics (NIDDM) patients before and
      after exercise].
AB  - To understand the effects of the levels of blood lipids and albumin on insulin
      receptor binding before and after acute exercise, we measured insulin binding to
      erythrocyt membrane before and after 30 minutes moderate exercise in thirty-eight
      non-obese noninsulin-dependent diabetics (NIDDM) and thirty-seven normal
      subjects. The correlations between parameters of insulin receptor and blood
      lipids and albumin were also studied. The results showed that before acute
      exercise, the level of high-binding-affinity (K1) was significantly correlated
      with that of total cholesterol (r = -0.473, P = 0.013), and albumin (r = -0.483,
      P = 0.011). The low-binding-affinity (K2) was significantly correlated with that
      of triglycerides (r = 0.503, P = 0.008) and high-density-lipoprotein (HDL)
      cholesterol (r = -0.480, P = 0.011). After acute exercise, no significant
      correlations between the parameters of insulin receptor, blood lipids and albumin
      were found. These suggest that blood lipids and albumin are important influential
      factors for affinities of insulin receptor.

PMID- 7584576
TI  - [Relation of bulging disc and herniated disc].
AB  - Fifteen lumbar bulging discs from 23 cadavers were examined by CT and
      histological technique, and 386 degenerating lesions in lumbar discs were studied
      if it has any relationship with degenerative diseases of intervertebral discs.
      Histologically, trasverse, concentric or/and radial tears were found in some
      anulus fibrosus of bulging discs. Clinically, the coexistence of bulging and
      hernia was noticed in a lesioned disc, we named it as "bulging and herniated
      disc", and the relation of which with bulging disc and herniated disc was
      discussed. This finding will change a well-known opinion that hernia would not
      occur in a bulging disc. Here bulging and herniated disc would reasonably be
      considered as one of degeneerative diseases of intervertebral discs.

PMID- 7584577
TI  - The behavioural sciences in the undergraduate curriculum: which department should
      teach them?

PMID- 7584578
TI  - A novel school dental screening programme.
AB  - The study validated a novel school dental screening test based on the
      professional and public belief that regular, or asymptomatic dental attendance is
      beneficial to oral health. A randomly selected group of 175, 14-15-year-old boys
      and girls were questioned about their dental attendance which was verified either
      by the dentists whom they claimed to visit or by further questioning those whose
      behaviour was not clear. This method of separating symptomatic from asymptomatic
      attenders had a sensitivity of 1.00 and a specificity of 0.72. The method was
      inexpensive and acceptable to both the school staff and the pupils. The
      preventive dental knowledge of both groups was high. Although the dental
      attitudes of the asymptomatic attenders were significantly better than those who
      attended symptomatically it was not possible to demonstrate with confidence that
      they had better dental health.

PMID- 7584579
TI  - Annual screening for oral cancer and precancer by invitation to 60-year-old
      residents of a city in Japan.
AB  - Since 1986, annual screening for oral cancer and precancer by postal invitation
      has been undertaken among 60-year-old residents of Tokoname city, Japan. Clinical
      examination of the oral soft tissues is performed by groups of four different,
      specially trained general dental practitioners in the city health centre on one
      day each year. Following screening each subject receives an individual
      consultation with an oral medicine specialist. Individuals considered to need
      full diagnostic follow up or treatment are advised to attend a secondary care
      referral facility. Between 1986 and 1993, 802 out of 5187 eligible residents
      (15.5 per cent) were screened of whom 38 (4.7 per cent) were designated by the
      screeners as positive for oral cancer, erythroplakia, leukoplakia, lichen planus
      or chronic candidosis. Of these, 32 were referred and 25 attended for follow up
      examination in hospital departments by specialists with full diagnostic back up
      facilities. Twenty subjects were confirmed as having a potentially malignant
      lesion. For these referred patients only, the proportion of correct decisions by
      the screeners out of all oral cancer/precancer screening decisions was 81 per
      cent. Positive and negative predictive values for those attending for follow up
      were 0.80 and 0.82 respectively. Ways of improving the effectiveness and adequacy
      of the programme are considered.

PMID- 7584581
TI  - The Modified Dental Anxiety Scale: validation and United Kingdom norms.
AB  - The Corah Dental Anxiety Scale (CDAS) has been used extensively in epidemiology
      and clinical research. It is brief and is claimed to have good psychometric
      properties. However, it does not include any reference to local anaesthetic
      injections, a major focus of anxiety for many. Also, the multiple choice answers
      for three of the four questions are not clearly in order of severity of anxiety
      as the CDAS intends. The answers differ among the questions thus making them
      difficult to compare. They include descriptions of physiological reactions and
      anxiety, confusing two loosely related components of the experience. The Modified
      Dental Anxiety Scale (MDAS) described, added a question on anxiety about oral
      injections. New multiple choice answers, in clear order of anxiety and the same
      for each question, were provided. Twenty five dental personnel all confirmed
      independently the order of the multiple choice answers for the MDAS. They
      disagreed among themselves however, about the appropriate sequence for the
      answers denoting intermediate anxiety in the CDAS. Therefore the CDAS, unlike the
      MDAS, can provide meaningful measures only of extremely high or extremely low
      dental anxiety. Of 1392 subjects tested, 13 per cent expressed extreme anxiety
      about injections on the MDAS but were only 'fairly' or less anxious about
      drilling. Thus, the CDAS, unlike the MDAS, must overlook subjects very afraid of
      injections only. Data confirm the high reliability and validity of the MDAS and
      provide norms for phobic and nonphobic subjects.

PMID- 7584580
TI  - The use of an index of material deprivation to identify groups of children at
      risk to dental caries in County Durham.
AB  - An investigation of the potential for an index of material deprivation to
      indicate groups of young children at risk to dental caries and to assess caries
      experience in their age group at three levels of deprivation, measured by the
      Townsend Index, was undertaken in County Durham. Electoral wards were ranked on
      an index of material deprivation derived from 1991 Census data. Dental caries
      data for the upper quartile, inter-quartile range and lower quartile of material
      deprivation in the County were obtained from a dental survey of 6052 five-year
      old children in 1991-92. The number of children in each group ranged from 1145 to
      3058. Significant differences in dental caries experience between high, middle
      and low ranges of material deprivation existed. The index of material deprivation
      can indicate groups of children in the community at high and low risk of dental
      caries.

PMID- 7584582
TI  - The pattern of patient attendance for emergency care in a British dental teaching
      hospital.
AB  - All new patients attending a dental hospital emergency clinic over a 10 week
      period were surveyed as to their reason for attendance. Six hundred and seven
      patients were seen and surveyed. Most complained of orofacial pain (77 per cent),
      swelling (22 per cent) or a lost restoration (21 per cent) but only 11 per cent
      had had their problem for less than one day. Most (60 per cent) had had symptoms
      for more than two days, and 29 per cent had had problems for more than 1 week.

PMID- 7584585
TI  - Differences in epidemiological findings when changing from the Anglepoise desk
      lamp to the Daray Versatile Medical Light.
AB  - The effect on epidemiological findings arising from changing from an Anglepoise
      desk lamp to a Daray Versatile Medical Light was studied using 155 school
      children aged between 11 and 14 years. The children were examined on separate
      days using the two types of illumination. Differences observed in DMFT, sealed
      teeth, gingival health, plaque and calculus were not significant. The mean DT (+/
      SE) was 0.12 (+/- 0.03) for the Anglepoise desk lamp and 0.16 (+/- 0.04) for the
      Daray Versatile Medical Light, the difference between these values being
      significant (P < 0.05). The magnitude of the difference was small (0.04 DT, SE +/
      0.02) when compared with observed changes in the mean DT in 15-year-old children
      in the districts where the study took place between 1986 and 1990. The level of
      agreement ranged from very good (kappa = 0.81-1.00) for DMFT and components to
      fair for plaque (kappa = 0.32). It is concluded that there is no evidence from
      this study that changing the type of illumination from Anglepoise desk lamp to
      Daray Versatile Medical Light would affect markedly the results of dental
      prevalence surveys.

PMID- 7584583
TI  - Estimation of procedure times in a publicly funded dental programme.
AB  - For the purposes of planning and evaluation, knowing the time-costs associated
      with each dental procedure carried out in a publicly funded dental programme is
      very helpful. This knowledge, along with the expected or known benefits, also
      allows researchers to assess the efficacy of a dental procedure. However, only a
      few estimates of dental procedure times exist in the literature, and most of
      these focus on restorative treatments. The North York Public Health Department
      operates a school-based public dental programme, where each dental procedure
      carried out by a dentist or hygienist is entered into a dental management
      information system database, along with the date of the procedure and the hours
      worked by the provider on that date. Using these data and multiple regression
      analyses it was possible to estimate the average time required to carry out the
      most common procedures in North York's dental programme. These estimates were
      found to be similar to estimates published in the dental literature and very
      similar to estimates of the Ontario Dental Association. Thus, this method of
      calculating procedure times appears valid and may be very useful to managers of
      public dental programmes and public dental health researchers.

PMID- 7584584
TI  - The dental health of 3-year-old children in east Cumbria 1993.
AB  - A study of the dental health of 135 3-year-old children, with reference to social
      class group, was undertaken in East Cumbria District between September and
      December 1993. Caries free subjects numbered 110 (81.5 per cent), the mean number
      of decayed, missing, and filled teeth was 0.59; the value of the decayed
      component of the dmft index was 0.49. Caries experience was confined to 25 (18.5
      per cent) individuals whose mean dmft was 3.20, seven of these subjects
      experienced rampant decay to the maxillary incisor teeth and three had received a
      dental general anaesthetic. An inverse relationship was demonstrated between
      dental caries and social class. Trauma to the maxillary incisors had occurred in
      17 (12.6 per cent) children, with discolouration and fracture of the enamel and
      dentine the most prevalent types of injuries sustained. A relatively high
      proportion of the subjects, 39 (28.9 per cent), had experienced erosion to
      palatal surfaces of the maxillary incisors. The most prevalent type of erosion
      was that involving both enamel and dentine. Only 14 (10.4 per cent) children
      examined used fluoride supplements in this low-fluoride area; 98 (72.6 per cent)
      subjects reported registration with a dentist.

PMID- 7584589
TI  - [Gastric rupture secondary to barotrauma in the framework of a diving accident.
      Apropos of a case report and literature review].
AB  - Gastric perforation secondary to barotrauma is rare. The case of a diver
      suffering from gastric rupture due to a decompression accident is presented here.
      This rupture was a linear one, localized on the lesser curvature and responsible
      for a large pneumoperitoneum. Rupture occurs with an excluded stomach, a
      condition implying cardio-pyloric occlusion. The expansion of intra-gastric air,
      further worsened by accelerated surfacing provokes excessive gastric dilatation
      leading to partial or complete rupture (by virtue of the Boyle-Mariotte law:
      Pressure x Volume = constant). The lesion is always on the lesser curvature.
      However, it is often difficult to locate, even when peroperative gastroscopy is
      performed.

PMID- 7584586
TI  - The NHS reform programme: implications for dental public health and the community
      dental services.
AB  - The structure and funding of the National Health Service in the United Kingdom
      has undergone major changes in recent years. A survey was conducted among senior
      personnel working within the dental public health and the community dental
      services to identify their roles and responsibilities, their views on the effects
      of the changes, and the future opportunities and challenges. A response rate of
      76 per cent was obtained using a postal questionnaire. In general the reforms
      were viewed as positive, although purchasers were consistently more optimistic
      than providers. The survey also highlighted that until the uncertainty
      surrounding the future direction of oral health care services has been clarified,
      the future role of senior personnel within the Community Dental Service and
      dental public health will remain unclear.

PMID- 7584588
TI  - [Small bowel injuries in blunt abdominal trauma--a diagnostic problem!].
AB  - AIMS: Injuries of the small bowel following a blunt abdominal trauma are rare
      (incidence 6%). The diagnosis is difficult and therefore often missed. The aim of
      this paper is to acquire an useful diagnostic sequence of our own results in
      comparison to the literature. METHODS: The diagnostic procedures and the time of
      the final diagnosis of 13 patients with this rare injury have been
      retrospectively analysed. RESULTS: Two of these 13 patients died in the emergency
      room. Five of the remaining 11 patients had signs of peritonitis at the first
      examination. These were confirmed by findings either in peritoneal lavage (3),
      ultrasound (1) or X-ray (1). Patients without signs of peritonitis revealed no
      pathological signs at the first examination with these diagnostic tools. Correct
      diagnosis was achieved on 7/11 patients within 24 hours. The diagnosis of small
      bowel injury was confirmed by the rest of the patients (n = 4) after an average
      of 11 days after trauma. DISCUSSION/CONCLUSION: Initial assessment with
      diagnostic tools as ultrasound, peritoneal lavage or X-ray is poor. Therefore
      repetitive controls (Nowadays by ultrasound) are indicated. The CT is a valuable
      tool to detect an organ lesion in hemodynamic stable patients with positive proof
      of liquid in the ultrasound. Today the value of the diagnostic laparoscopy is not
      established. It should be considered that a local ischemia due to the blunt
      trauma can cause a delayed perforation.

PMID- 7584590
TI  - [Splenic neoformation following trauma-induced splenectomy--diagnosis and
      function].
AB  - GOAL: Regeneration of the spleen after posttraumatic splenectomy has been
      described in the literature. The goal of this study was to determine the rate of
      splenosis, its effect on hematology and postoperative infections and the value of
      sonography in the diagnosis of splenosis. PATIENTS AND METHODS: Fifty patients
      were examined sonographically one to 14 years after splenectomy. They were
      questioned concerning infections and a blood count was done. Data concerning the
      grading of the splenic rupture, additional injuries and postoperative
      complications were collected from their charts. RESULTS: Splenosis was detected
      sonographically in 17 patients. It was seen more often, the more severe the
      injury of the spleen had been. Patients under 30 years in the splenosis group had
      a shorter ICU and hospital stay and significantly less postoperative infections.
      Fourteen of 17 patients with splenosis had no hematological changes, while 32 of
      33 patients without splenosis demonstrated Howell-Jolly bodies and acanthocytes.
      CONCLUSIONS: Sonography is a reliable method for visualisation of splenosis. The
      latter seems to prevent the hematological changes usually found after
      splenectomy. It also seems to reduce the number of postoperative infections in
      young patients.

PMID- 7584591
TI  - [Dynamic skin suture for secondary skin closure and treatment of skin defects].
AB  - Dynamic skin suture exerts progressive traction to the wound margins which allows
      a stepwise closure of a defect. It consists of interrupted sutures with two
      additional plastic tubes lying parallel to the wound margins on the surface of
      the skin. The extracuticular slopes of the sutures and the knots pass over these
      tubes. This decreases local pressure on the skin. The knots are performed in a
      way that, once they have been tied, permits further tightening without opening
      them. A viscoelastic property of the skin--stress-relaxation- reduces the tension
      on the sutures over time and allows a further tightening. As an example for the
      use of this technique, the results of closures of fasciotomies in compartment
      syndromes are presented. In 1993, 50 fasciotomies in 35 patients were treated
      with dynamic suture. In 42 defects (84%) a complete obliteration was possible. In
      the residual 8 defects reduction of size was significant. The mean time until
      obliteration was 11.5 days, in average sutures were tightened 4 times. The
      results suggest that dynamic suture is a useful technique for repair in
      fasciotomies. It helps avoiding tissue transplantations. The operative procedure
      itself is speedy and simple. Possible indications in limited excisional defects
      are demonstrated in a case report.

PMID- 7584587
TI  - Presidential address to the British Association for the Study of Community
      Dentistry, Warwick, April 1995.

PMID- 7584592
TI  - [Increased plasma level of Type I (p55) and Type II (p75) TNF-receptors following
      trauma].
AB  - Excessive synthesis and release of proinflammatory cytokines following trauma
      have been correlated with poor outcome of injured patients. TNF-alpha seems to
      play a pivotal role as trigger for the induction of systemic inflammation.
      Recently, two naturally occurring inhibitors of TNF-alpha, soluble TNF-receptors
      (sTNFRs) p55 and p75, have been characterized. The present study was undertaken
      to determine whether severe trauma increases circulating sTNFRs dependent on
      severity of injury. Injured patients (n = 190) revealed significantly increased
      plasma levels of both sTNFRs throughout the observation period of 21 days
      compared to healthy volunteers (n = 125). Patients with severe injury (ISS > 16
      pts; n = 130) revealed higher (p < 0.0001) levels of sTNFRs on day of admission
      than patients with minor trauma (< or = 16 pts; n = 60). Thus, anti-inflammatory
      mechanisms are activated during the posttraumatic course dependent on severity of
      injury.

PMID- 7584594
TI  - [Interlocking nailing of the tibia].
AB  - Centromedullary nailing is a well-established method of treatment for diaphyseal
      long bone fractures. The indications have been broadened greatly since the
      introduction in 1974 of interlocking centromedullary nailing. The purpose of this
      paper is to review our first results with locked intramedullary nailing of the
      tibia. We report our experience with the first 19 cases of interlocking tibia
      nails (15 fractures, 1 delayed union, 2 pseudarthrosis, 1 osteotomy). On the
      extension table, the insertion of the nail and the placement of the interlocking
      screws did not cause any problem. In 3 cases, a proximal screw had to be removed
      within two weeks because of spontaneous displacement. Complications have been
      noticed in three patients (15.8%) (pulmonary embolism on day 1, and compartment
      syndrome two days later in one case, sciatic nerve neuroapraxia in the other
      two). The other patients have been mobilized 24 to 48 hours after surgery. 94% of
      the fractures were consolidated 4 months post-operatively, with no major
      deformation. Interlocking tibia nailing seems to be an attractive method in the
      treatment of certain fractures of the tibia. Early mobilisation and weight
      bearing are provided. The indications, the technical aspects as well as the
      dangers of the method must be carefully respected in order to avoid complications
      and poor results.

PMID- 7584593
TI  - [Determination of serum lead levels following shotgun injury].
AB  - Lead concentration of pellets is over 95%. Four patients who had sustained
      shotgun injury with retained shotgun bullets in the body are described. In 3 of 4
      patients the blood level of lead was increased, as well as the concentration of
      Delta-ALA in the urine. In all four patients symptoms due to lead intoxication
      were absent. Usually the surgical goal is limited to a proper debridement of
      large wounds in the soft tissue. Therefore it is mandatory to assess the lead
      level in the blood and the concentration of Delta-ALA in the urine. Thus
      asymptomatic lead intoxication can be recognized and treated.

PMID- 7584595
TI  - The unique structures of protozoan myoglobin and yeast hemoglobin: an
      evolutionary diversity.
AB  - A hemoglobin-like protein is found in some of the single-celled organisms, but
      its structure is quite different from that of mammalian myoglobin or hemoglobin.
      For instance, a protozoan myoglobin isolated from Paramecium caudatum consists of
      116 amino acid residues, so that this contracted form is nearly two thirds of
      sperm whale myoglobin. Yeast hemoglobin from Candida norvegensis, on the other
      hand, is composed of a single polypeptide chain with 387 amino acid residues, but
      of two distinct domains carrying different functions; that is the N-terminal,
      heme-containing region and the C-terminal, FAD-containing reductase domain. The
      very unique structures of these ancient hemoproteins tell us their own strategies
      to overcome many difficulties in the reversible and stable binding of molecular
      oxygen, a very strong oxidizing agent, to the heme iron(II) in aqueous solutions.

PMID- 7584596
TI  - Syngeneic anti-idiotypic monoclonal antibodies against an anti-human chorionic
      gonadotrophin antibody.
AB  - Monoclonal antibody designated 1B10 (Mab 1B10) has been shown to be highly
      specific for the beta-chain of human chorionic gonadotrophin (HCG). We used this
      antibody to investigate its paratope using anti-idiotypic antibodies. Purified
      Mab 1B10 has been used to immunize syngeneic BALB/c mice to produce anti
      idiotypic monoclonal antibodies. An enzyme immunoassay (ELISA) on Mab 1B10 coated
      plate was employed to screen the supernatants of growing hybridomas. The
      specificity of each antibody selected was assessed using an inhibition ELISA and
      immunoblotting. Monoclonal antibodies belonging to two categories were selected.
      (a) Those (designated Mab 4F8 and Mab 7G9) recognizing epitopes of the Ig
      molecule located in/or near the antigen-binding site of Mab 1B10. In ELISA these
      antibodies were shown to inhibit in a dose-dependent manner, the reaction of Mab
      1B10 with its specific antigen; (b) those (Mab 2B8, Mab 3B8) reacting with
      epitopes located outside of the antigen binding site of the antiHCG antibody
      molecule and did not influence the reactions of Mab 1B10 and its antigen.
      Following immunization of syngeneic BALB/c mice monoclonal antibodies (Mab 4F8,
      Mab 7G9) were produced which recognized epitopes located on the variable region
      of Mab 1B10 since they did not react with other murine monoclonal antibodies of
      the same isotype. These antibodies inhibited the binding of Mab 1B10 to its
      corresponding epitope on the molecule of HCG and they can be defined as syngeneic
      anti-idiotypic antibodies.

PMID- 7584597
TI  - Interaction of calcyclin and its cyanogen bromide fragments with annexin II and
      glyceraldehyde 3-phosphate dehydrogenase.
AB  - The structural properties of calcyclin protein are quite well characterized but
      its function remains obscure. To help elucidate the biological role of calcyclin
      we have performed the in vitro studies of the Ca(2+)-dependent interaction of
      Ehrlich ascites tumor cells calcyclin and its cyanogen bromide fragments with two
      potential calcyclin targets: annexin II and glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH). The binding of annexin II, evidenced by the reaction with
      125I-calcyclin, was found to be very weak and occurred only for intact calcyclin.
      On the other hand the interaction between calcyclin and GAPDH was of high
      affinity and could be assigned to the N-terminal region of calcyclin. Intact
      calcyclin and its N-terminal fragment bound to GAPDH in the gel overlay and
      affinity chromatography assay. When examined in the presence of a crosslinking
      agent the interaction resulted in the formation of 46K covalent adduct between
      calcyclin monomer and GAPDH subunit. Fluorescence of 5-iodoacetamido-fluorescein
      labelled calcyclin was efficiently quenched by GAPDH in the presence of Ca2+.
      Titration experiments revealed the stoichiometry of one calcyclin monomer binding
      to each of GAPDH subunits with a binding constant of 10(8) M-1. The results of
      this work suggest that the binding between calcyclin and GAPDH may have bearing
      on calcyclin function.

PMID- 7584598
TI  - Palmitoylation of brain capillary proteins.
AB  - Palmitoylation is a reversible posttranslational modification which is involved
      in the regulation of several membrane proteins such as beta 2-adrenergic
      receptor, p21ras and trimeric G-protein alpha-subunits. This covalent
      modification could be involved in the regulation of the numerous membrane
      proteins present in the blood-brain barrier capillaries. The palmitoylation
      activity present in brain capillaries was characterized using [3H]palmitate
      labeling followed by chloroform methanol precipitation. Palmitate solubilizing
      agents such as detergents and bovine serum albumin (BSA), were used for
      optimizing activity. Some palmitoylated substrates were identified using
      [3H]palmitate labeling followed by immunoprecipitation with specific antibodies.
      Two optimal palmitate solubilization conditions were found, one involves cell
      permeabilization (Triton X-100) and the other represents a more physiological
      condition where membrane integrity is conserved (BSA). Sensitivity to the
      cysteine modifier N-ethylmaleimide and to hydrolysis, using hydroxylamine or
      alkaline methanolysis, indicated that palmitic acid was bound to the proteins by
      a thioester bond. Maximal palmitate incorporation was reached after 30 or 60 min
      of incubation in the presence of Triton or BSA, respectively. Depalmitoylation
      was observed in the presence of BSA, but not with detergents. The palmitoylation
      reaction was optimal at pH 8 or 9 in the presence of Triton or BSA, respectively,
      but palmitoylated substrates were detectable over a wide range of pH values. In
      the presence of Triton X-100, the addition of ATP, CoA and Mg2+ to the incubation
      medium increased palmitoylation by up to 80-fold. Two palmitoylated substrates
      were identified, a 42 kDa G-protein alpha subunit and p21ras. The study shows
      that the utilization of palmitate solubilizing agents is essential to measure in
      vitro palmitoylation in brain capillaries. Several palmitoylated proteins are
      present in the blood-brain barrier including five major substrates of 12, 21, 35,
      42 and 55 kDa. It is suggested that palmitoylation could play a crucial role in
      the regulation of brain capillary function, since the two substrates identified
      in this study are known to be involved in signal transduction, vesicular
      transport and cell differentiation.

PMID- 7584599
TI  - Purification and properties of the pyruvate kinase isozyme M1 from the pig brain.
AB  - There are four pyruvate kinase isozymes in vertebrate tissues, designated as L,
      M1, M2, and R. Although pyruvate kinases have been purified and characterized
      from pig liver, muscle, kidney, and heart, the brain isozyme has not. The aim of
      this work was to purify, characterize and make an isozymic designation for the
      pig brain pyruvate kinase. Purification was accomplished by chromatography on
      phosphocellulose, Sephadex G200, and blue-dextran agarose columns. The molecular
      weight of the native enzyme was determined by sucrose density centrifugation. The
      degree of purity, and subunit molecular weight were determined by polyacrylamide
      gel electrophoresis in sodium dodecyl sulfate. The isoelectric point was
      estimated by the rapid isoelectric focusing method in sucrose gradients. The pH
      optimum, and kinetics in the presence and absence of fructose-1,6-diphosphate
      were determined spectrophotometrically. The purification scheme used resulted in
      a 382-fold purification of pig brain pyruvate kinase, and a final specific
      activity of 191 Units/mg protein. As estimated by scanning of the sodium dodecyl
      sulfate polyacrylamide gels, the purification scheme also resulted in a
      preparation that was of at least 98% purity. Pig brain pyruvate kinase has a
      native molecular weight of approx. 230,000, and a subunit molecular weight of
      approx. 60,000. The pI was determined to be approximately 8.0, while the pH
      optimum was estimated at pH 7.4. Fructose-1,6-diphosphate had no effect on either
      the Km for phospho(enol)pyruvate, or the Vmax of the reaction.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7584600
TI  - Depletion of urate in human nasal lavage following in vitro ozone exposure.
AB  - Ozone, a strong oxidant present in summer smog, is thought to primarily react
      with antioxidant molecules found in the epithelial lining fluid of the
      respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in
      the nasal cavity where the major extracellular antioxidant has been identified as
      uric acid. The present study was undertaken to examine urate/oxidant interactions
      in human nasal lavage fluid following in vitro exposure to ozone at
      concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers
      using a modified Foley catheter which permits prolonged contact of isotonic
      saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates
      were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were
      removed at intervals from 15 to 240 min following exposure and assayed for uric
      acid depletion. Uric acid concentrations in the nasal lavage were found to fall
      from 8.52 (time zero) to 3.99 microM, 0.05 and 0.07 microM after 240 min at 50,
      100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone
      concentration of 1000 ppb, uric acid was completely depleted after 60 min.
      Regression analysis showed a linear correlation between rate of loss of urate and
      ozone concentration (R2 = 0.97). A novel, non-invasive technique is described to
      investigate antioxidant compromise and its importance in individual subjects. We
      conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose
      and time dependent manner.

PMID- 7584605
TI  - Glucose-induced phosphorylation and activation of a high molecular weight
      cytosolic phospholipase A2 in neonatal rat pancreatic islets.
AB  - Previous studies have shown that stimulus-secretion coupling for the release of
      insulin from the pancreatic islet is potentiated by phospholipase A2 activity.
      Several biochemically distinct phospholipase A2 activities have been described in
      the islet. A recently identified cytosolic high molecular weight phospholipase
      A2, which requires Ca2+ for association with cellular membranes but not for
      catalytic activity can be activated in a protein kinase C-dependent manner in
      other cell-types. We determined its phosphorylation and activation in response to
      phorbol ester and glucose in cultured islet cells from neonatal rats. Islet cell
      monolayers were labelled to equilibrium with [32P]orthophosphate. Following
      stimulation cytosolic phospholipase A2 was immunoprecipitated and, after
      electrophoretic separation and transfer to nitrocellulose membrane, 32P-labelled
      protein was detected by autoradiography. Phospholipase A2 activity of islet cell
      cytosol was determined by hydrolysis of exogenous I-stearyl- 2[14C]arachidonyl
      phosphatidylcholine substrate. It could be shown that phosphorylation of
      immunoprecipitated phospholipase A2 was augmented by prolonged glucose exposure
      (> 1 hr) in a protein kinase C-dependent manner. Phosphorylation occurred
      concomitant with a glucose-induced increase in total cellular phospholipase A2
      activity (177 +/- 3 nmol substrate hydrolysed/mg protein at glucose 5.6 mM vs 267
      +/- 32 (SEM, n = 4) at glucose 25 mM, P < 0.05). Both acute protein kinase C (459
      +/- 71) and glucose-activated phospholipase A2 activities were reduced in the
      presence of a specific arachidonic acid analogue inhibitor of cytosolic
      phospholipase A2 (to 231 +/- 10 and 161 +/- 17, respectively).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7584602
TI  - Thermostability of lactate dehydrogenase LDH-A4 isoenzyme: effect of heat shock
      protein DnaK on the enzyme activity.
AB  - Cells exposed to temperature a few degrees higher than their growth temperature
      synthesize heat shock proteins (hsp) which may then compose even 20% of total
      protein content. This paper examined the in vitro protective effect of heat shock
      protein DnaK (70 kDa) from Escherichia coli against the heat inactivation of
      lactate dehydrogenase isoenzyme LDH-A4. The LDH-A4 isoenzyme was purified from
      fish skeletal muscle using the affinity chromatography on Oxamate-agarose. The
      enzyme was then heated in the absence and the presence of DnaK protein in a water
      bath at either 51 or 55 degrees C. The LDH activity was determined by measuring
      the change in absorbency at 340 nm min-1 at 30 degrees C. The addition of DnaK
      protein to the LDH-A4 isoenzyme before heat treatment can protect enzyme activity
      against mild thermal inactivation. Incubation of the LDH-A4 isoenzyme at 51
      degrees C in the presence of DnaK protein stimulates its activity by about 30%.
      The presence of 2 mM ATP can raise LDH activity by another 10%. No significant
      recovery was observed when DnaK protein was added to LDH at 25 degrees C
      following earlier inactivation. The maximal activities (Vmax) in the presence of
      DnaK protein are almost twice those without DnaK protein in the case of heat
      treated LDH-A4 isoenzyme at 51 degrees C. The observed protection of LDH-A4
      activity increased with the increasing DnaK protein concentration in the
      incubation medium. Results suggested that the presence of DnaK protein can
      protect LDH-A4 from heat inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584601
TI  - Effect of prolonged starvation on the activities of malic enzyme and
      acetylcholinesterase in tissues of Japanese quail.
AB  - During starvation muscle protein degradation is increased but the mechanism for
      this is uncertain. In this study Japanese quail were starved for 5 days and the
      activities of malic enzyme and acetylcholinesterase were determined in various
      tissues. SDS-polyacrylamide gel electrophoresis showed that the soluble proteins
      with molecular weights corresponding to 160, 120, 108, 99 and 38 kDa were absent
      in the liver of the starved group. In the pectoral muscle the soluble proteins
      with molecular weights corresponding to 69, 41 and 34 kDa were missing. The
      activity of malic enzyme in the liver, heart and pectoral muscle of the starved
      group decreased markedly whereas that of acetylcholinesterase increased markedly
      in the pectoral muscle (P < 0.005). It is concluded that in prolonged starvation
      acetylcholinesterase synthesis may be induced in tissues being subjected to
      protein catabolism and that this enzyme may be involved as a protease in protein
      degradation.

PMID- 7584604
TI  - Energetics of heart mitochondria during acute phase of Trypanosoma cruzi
      infection in rats.
AB  - The energetics of heart mitochondria was studied in the acute phase of
      Trypanosoma cruzi infection in rats. Wistar rats were infected with 2 x 10(5)
      trypomastigote forms of the Y strain of T. cruzi, and heart mitochondria and
      submitochondrial particles isolated after 7 and 25 days of infection.
      Ultrastructure of mitochondria seemed to be preserved, but cytochrome c levels
      were significantly depressed. Respiratory control ratios (RCR) were decreased for
      glutamate and succinate oxidations, as a consequence of inhibition of respiration
      in state 3 and/or of stimulation of respiration in state 4. Stimulation of
      hydrolytic activity of FoF1-ATPase by energization of mitochondria was approx. 2
      fold higher in relation to controls. Mitochondrial ATP concentration remained
      constant. In conclusion, during the acute phase of T. cruzi infection in rats
      there is an energy impairment at the level of heart mitochondria, but their
      ultrastructure and ATP concentration seem to be preserved; the maintenance of ATP
      may be due to an adaptative mechanism of the cell which includes inhibition of
      the hydrolytic activity of FoF1-ATPase.

PMID- 7584603
TI  - Vitamin E protects guinea pig liver from lipid peroxidation without depressing
      levels of antioxidants.
AB  - Oxidative stress is considered a pathogenic factor in many disorders. The
      capacity of dietary vitamin E to increase global antioxidant capacity and to
      decrease lipid peroxidation was studied in the guinea pig, an animal that cannot
      synthesize ascorbate. Male guinea pigs were subjected for 5 weeks to three diets
      differing in vitamin E content in the presence of optimum levels of vitamin C:
      group 15 (15 mg vitamin E/kg diet), group 150 (150 mg/kg), and group 1500 (1500
      mg/kg). Hepatic vitamin E increased in the three groups in relation to the level
      of vitamin E in the diet. The increase in vitamin E between groups 15 and 150 was
      accompanied by a reduction in sensitivity to enzymatic lipid peroxidation. This
      did not occur between groups 150 and 1500. The different liver vitamin E
      concentrations did not affect the antioxidant enzymes superoxide dismutase,
      catalase, GSH-peroxidase and GSH-reductase, nor the non-enzymatic antioxidants
      vitamin C, GSH and ascorbate. It is concluded that dietary supplementation with
      vitamin E, at a level 6 times higher than the minimum daily requirement for
      guinea pigs, increases protection against hepatic lipid peroxidation without
      depressing endogenous antioxidant defences. Further increases in vitamin E to
      megadose levels did not provide additional protection from oxidative stress. The
      results also suggest that optimum levels of both vitamin C and vitamin E,
      simultaneously needed for protection against oxidative stress, are much higher
      than the minimum daily requirements.

PMID- 7584606
TI  - Purification and kinetic characterization of gamma-aminobutyraldehyde
      dehydrogenase from rat liver.
AB  - Oxidative deamination of putrescine, the precursor of polyamines, gives rise to
      gamma-aminobutyraldehyde (ABAL). In this study an aldehyde dehydrogenase, active
      on ABAL, has been purified to electrophoretic homogeneity from rat liver
      cytoplasm and its kinetic behaviour investigated. The enzyme is a dimer with a
      subunit molecular weight of 51,000. It is NAD(+)-dependent, active only in the
      presence of sulphhydryl compounds and has a pH optimum in the range 7.3-8.4.
      Temperatures higher than 28 degrees C promote slow activation and the process is
      favoured by the presence of at least one substrate. Km for aliphatic aldehydes
      decreases from 110 microM for ABAL and acetaldehyde to 2-3 microM for
      capronaldehyde. The highest relative V-values have been observed with ABAL (100)
      and isobutyraldehyde (64), and the lowest with acetaldehyde (14). Affinity for
      NAD+ is affected by the aldehyde present at the active site: Km for NAD+ is
      approximately 70 microM with ABAL, approximately 200 microM with isobutyraldehyde
      and capronaldehyde, and > 800 microM with acetaldehyde. The kinetic behaviour at
      37 degrees C is quite complex; according to enzymatic models, NAD+ activates the
      enzyme (Kact approximately 500 microM) while NADH competes for the regulatory
      site (Kin approximately 70 microM). In the presence of high NAD+ concentrations
      (4 mM), ABAL promotes further activation by binding to a low-affinity regulatory
      site (Kact approximately 10 mM). The data show that the enzyme is probably an E3
      aldehyde dehydrogenase, and suggest that it can effectively metabolize aldehydes
      arising from biogenic amines.

PMID- 7584608
TI  - Fibrillin-containing microfibrils: structure and function in health and disease.
AB  - Fibrillin-containing microfibrils are a unique class of connective tissue
      macromolecules whose critical contribution to the establishment and maintenance
      of diverse extracellular matrices was underlined by the recent linkage of their
      principal structural component fibrillin to Marfan syndrome, a heritable disorder
      with pleiotrophic connective tissue manifestations. The complexity of the
      structure: function relationships of these macromolecules was highlighted by the
      recent elucidation of the primary structure of fibrillin and characterisation of
      fibrillin mutations in Marfan patients. This review examines current
      understanding of the expression and assembly of fibrillin and describes new
      approaches which are now being applied to elucidate the many outstanding
      structural, organisational and functional aspects of the fibrillin-containing
      microfibrils.

PMID- 7584607
TI  - Recent advances in the metabolism of cannabinoids.
AB  - This review describes recent advances in the metabolism of cannabinoids.
      Cannabidiol was metabolized to cannabielsoin, 6 beta-hydroxymethyl-delta 9
      tetrahydrocannabinol and an oxepine derivative through epoxide intermediates by
      hepatic microsomal enzymes containing cytochrome P450 of animals. Cannabidiol
      inactivated cytochrome P450 UT-2 (CYP2C11) not equal to in male rats and a member
      of 3A subfamily in mouse liver. These inactivations may be very important because
      serious drug-drug interactions will occur in the case that cannabidiol is co
      administered with drugs which are metabolized mainly by the enzyme system
      containing these P450 isozymes. A member of cytochrome P450 belonging to 2C
      subfamily was the major isozymes responsible for the cannabinoid metabolism in
      many experimental animals and that of 3A subfamily made some contribution to the
      metabolism of cannabinoids by human hepatic microsomes. Microsomal aldehyde
      oxygenase, a particular isozyme of cytochrome P450 catalyzing the oxidation of 11
      oxo-tetrahydrocannabinol to tetrahydrocannabinol-11-oic acid, was found for the
      first time by the authors. Cytochrome P450 MUT-2 (CYP2C29) is the major isozyme
      responsible for the microsomal aldehyde oxygenase activity in mouse hepatic
      microsomes.

PMID- 7584609
TI  - In vitro adsorption of amino acids onto isolated rat erythrocyte membranes.
AB  - Amino acids adsorbed onto blood cell membranes represent about 8% of the total
      amino acids in blood. The aim of this study was to determine the in vitro
      adsorption kinetics of different amino acids (L-alanine, glycine, L-glutamate, L
      glutamine, L-phenylalanine and L-leucine) onto rat erythrocyte membranes and to
      assess the effect of 24-hr starvation on these adsorption kinetics. Isolated red
      cell membranes were incubated at 37 degrees C for 10 sec in the presence of 14C
      amino acids--with different specific radioactivity--the radioactivity retained in
      the membrane fraction measured and kinetic parameters of amino acid adsorption
      determined. With the exception of glutamate, where the adsorption was negligible,
      all amino acids studied were adsorbed onto isolated red cell membranes, adhering
      to simple Michaelis-Menten kinetics. Km' values of glycine, phenylalanine and
      leucine adsorption in control rats (14.7 +/- 3.8 mM, 8.41 +/- 0.95 mM and 4.65 +/
      0.46 mM respectively, SEM, n = 6-8) decreased in response to 24-hr starvation,
      giving the following values: 0.792 +/- 0.122 mM, 5.32 +/- 0.82 mM and 3.53 +/-
      0.31 mM respectively (SEM, n = 6-8), Vmax' value of glycine adsorption of control
      rats decreased (from 61.0 +/- 15.5 mmol/mol P/sec to 4.25 +/- 0.70 mmol/mol
      P/sec, SEM, n = 7) and that of leucine increased (from 13.5 +/- 1.0 mmol/mol
      P/sec to 18.9 +/- 2.0 mmol/mol P/sec, SEM, n = 7) as an effect of 24-hr
      starvation. This study shows that alanine, glycine, glutamine, phenylalanine and
      leucine, but not glutamate, adsorbed onto erythrocyte membranes according to
      Michaelis-Menten-like kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584610
TI  - Quantitation of protein phosphatase 1 and 2A in extracts of the budding yeast and
      fission yeast.
AB  - Serine/threonine protein phosphatases are also involved in the control of cell
      division. The aim of the present study was to compare the activity of protein
      phosphatase 1 (PP1) and 2A (PP2A) in cell extracts of the budding and fission
      yeast, made at different phases of growth. The activities of PP1 and PP2A toward
      phosphorylase were similar in extracts of S. cerevisiae. In S. pombe extracts,
      PP1 was responsible for more than 80% of the phosphorylase phosphatase activity.
      Ammonium sulfate-ethanol treatment increased the specific activity of the
      phosphatases and the percentage of PP2A in S. cerevisiae extracts. No increase in
      the proportion of PP2A was observed upon the same treatment of S. pombe extracts.
      The above results were confirmed by fractionation of PP1 and PP2A activities on a
      heparin-Sepharose column. The proportion of PP1 and PP2A activities did not
      change significantly during exponential cell growth but cells from stationary
      phase exhibited lower phosphatase activities. These results may indicate a lower
      level of expression of the PP2A genes in S. pombe and/or differences in the
      structure of the holoenzymes or their regulators in the two genera.

PMID- 7584611
TI  - Immunoquantification of type I, III, IV and V collagen in small samples of human
      lung parenchyma.
AB  - The involvement of collagen in pathological conditions underscores the need for
      sensitive, collagen type-specific assays. A method for the quantification of
      different types of collagen in lung has been developed. Human lung parenchyma is
      digested with cyanogen bromide which results in almost complete solubilization of
      collagen to type-specific collagen peptides. The peptides are quantified using
      inhibition enzyme immunoassays with type-specific antibodies. The 50% inhibition
      value for the type I collagen assay is 1 microgram type I collagen peptides, for
      the type III collagen assay 350 ng type III collagen peptides, for the type IV
      collagen 200 ng type IV collagen peptides, and for the type V collagen assay 50
      ng type V collagen peptides. Using less than 1 mg lyophilized human parenchymal
      lung tissue it was established that the amount of collagen/mg dry tissue (+/- SD,
      n = 10) is 84.6 +/- 16.1 micrograms for type I collagen, 26.6 +/- 10.3 micrograms
      for type III collagen, 9.6 +/- 2.0 micrograms for type IV collagen and 1.8 +/-
      0.3 micrograms for type V collagen. The procedure is useful for the
      quantification of different types of collagen, including minor collagens, and
      requires only minimal sample preparation.

PMID- 7584612
TI  - The effect of spermine on calcium requirement for protein kinase C association
      with phospholipid vesicles.
AB  - We have previously reported that polyamines interfere with protein kinase C
      membrane interactions. With the aim of clarifying the influence of the
      relationship between calcium and polyamines on this process we have investigated
      the effect of spermine on the formation of active protein kinase C-membrane
      complexes as a function of Ca++ concentrations. Protein kinase C, purified from
      rat brain, was allowed to interact with phospholipid vesicles of defined
      composition. The active complex protein kinase C-liposomes was determined by its
      ability to bind radioactive phorbol ester with an exact 1:1 stoichiometry. The
      results show that, at Ca++ levels below 0.1 microM, spermine inhibits the
      formation of complexes between protein kinase C and membranes. At higher Ca++
      concentrations, spermine does not prevent the association process but does
      influence the ratio between the enzyme molecules irreversibly inserted into the
      membrane and those reversibly associated with it. We have also demonstrated that
      spermine, by reducing the density of acidic component of liposomes, influences
      the calcium requirement for protein kinase C-membrane binding. This study
      indicates that spermine may regulate the activation of protein kinase C and
      affects the calcium requirement for the association of this enzyme with the
      phospholipid bilayer. The results suggest a possible role for polyamines in
      signal transduction when protein kinase C is involved.

PMID- 7584615
TI  - Effects of glucosamine on insulin-stimulated glucose metabolism in rat soleus
      muscle.
AB  - Intracellular accumulation of glucosamine metabolites (which can be achieved by
      pre-incubation of cells with glucosamine) during hyperglycaemia may decrease the
      rate of insulin-mediated glucose transport in cells. Soleus muscle preparations
      were pre-incubated in the presence or absence of glucosamine in media that
      contained glutamine (Dulbecco's modified Eagle medium, DMEM; Medium 199, M199) or
      devoid of glutamine (Krebs-Henseleit's buffer, KHB). Subsequently, muscles were
      transferred to fresh media, in the absence of glucosamine, but with various
      concentrations of insulin and the rates of 2-deoxyglucose transport or
      intracellular glucose metabolism were measured. Glucosamine pre-exposure
      decreased both insulin-stimulated (1000 microU/ml) glucose transport and
      phosphorylation. The percentage decreases for 3H-2-deoxyglucose transport after
      pre-incubation with 40 mM glucosamine compared with untreated muscles were: DMEM,
      48%; KHB, 50%; M199, 29%. The percentage decreases for 3H-2-deoxyglucose-6
      phosphate accumulation were: DMEM, 53%; KHB 60%; M199, 37%. In DMEM and KHB,
      glucosamine pre-treatment of soleus muscle preparations markedly decreased the
      rate of lactate release and stimulated the rate of 14C-glucose incorporation into
      glycogen. Thus, a distinct shift of glucosyl units from glycolysis to
      glycogenesis occurred with low and high insulin concentrations. For the latter
      (1000 microU of insulin/ml) the ratio of moles of glucose converted to lactate
      divided by moles of glucose incorporated into glycogen in muscles pre-incubated
      in the absence or presence of glucosamine (40 mM) was, respectively: DMEM, 4.34 +
      0.52 vs 1.55 + 0.06, P < 0.001; KHB, 2.80 + 0.44 vs 0.76 + 0.03, P < 0.005).
      Glycogen synthesis was not stimulated in muscles pre-exposed to glucosamine in
      M199. In muscles pre-incubated to glucosamine and incubated in DMEM or KHB, there
      was a marked shift of glucose transported into the cell from glycolysis to
      glycogenesis. Thus, glucosamine or its metabolites had distinct effects on
      intracellular glucose handling.

PMID- 7584616
TI  - The local and systemic effects of minor injury on muscle protein synthesis in the
      rat.
AB  - Massive physical trauma has marked effects on metabolism of body tissues. At
      present, however, there is little data available on the effect of minor injury on
      protein metabolism. In this study we examined the effects of a minor muscle
      injury on the rate of protein synthesis in injured muscle as well as its
      contralateral control. Rats were injured by removing a small piece of tissue from
      the interior of one gastrocnemius muscle. Muscle protein synthesis was measured
      in vivo by a flooding dose technique. The injury had no significant effect on
      food intake, body weight, muscle protein content or plasma insulin concentration
      at any time during the following 48 hr. However the rate of protein synthesis in
      the injured muscle increased 48 hr after injury (mean value in injured muscle
      16.1 +/- 1.8 (SEM, n = 18) % per day, uninjured muscle in the same animals 13.1
      +/- 1.3% per day, P < 0.05 by paired t-test). These results indicate that even a
      minor injury causes a local increase in the rate of protein synthesis 48 hr
      later. This may be an obligatory part of the process of repair and regrowth of
      muscle tissue.

PMID- 7584614
TI  - The effect of osmolarity on human placental mitochondria function.
AB  - Human placental explants survive large changes in osmolarity, but the mechanism
      for this property is unknown. The goal of this work was to examine the effect of
      osmolarity on human placental mitochondria. Mitochondria from human term placenta
      were isolated by differential centrifugation, and incubated in the presence of
      different concentrations of sucrose or KCl, to modify the osmolarity of the
      media. Rat liver mitochondria were used as control. The parameters studied were:
      respiration rate, adenine nucleotide hydrolysis, calcium transport, membrane
      potential, and mitochondrial morphology. Stimulation of the mitochondrial
      respiration rate and an increase in Ca2+ transport was observed in the presence
      of K+. With sucrose, Ca2+ transport showed a complex kinetic behavior, whereas
      the respiratory control was slightly diminished. Although the ATPase activity was
      enhanced in the absence of a respiratory substrate, no change in ATP hydrolysis
      due to osmolarity was observed. ADP hydrolysis was inhibited by a high K+
      concentration, but not by sucrose. The membrane potential was not modified by
      osmolarity, even in the absence of sucrose or K+ in the medium. Mitochondria
      isolated with KCl showed aggregation, whereas dispersed mitochondria were
      observed with sucrose. This study showed that sucrose-induced changes in
      osmolarity, does not modify metabolic and transport properties of human placental
      mitochondria, whereas KCl-induced osmolarity changes does affect these functions.

PMID- 7584617
TI  - Enzymatic control of glycogenolysis during anoxic submergence in the freshwater
      turtle Trachemys scripta.
AB  - Freshwater turtles Trachemys scripta elegans endure prolonged severe hypoxia, and
      even complete anoxia, while diving or hibernating underwater. Metabolic
      adaptations supporting survival include the activation of glycogenolysis and
      glucose output from liver, as well as strong metabolic rate depression. The
      present study analyzes the enzymes of both the phosphorolytic (glycogen
      phosphorylase, phosphorylase b kinase, cAMP-dependent protein kinase) and
      glucosidic (alpha-glucosidase) pathways of glycogenolysis in turtle organs.
      Turtles were subjected to 5 hr of submergence in N2-bubbled water at 7 degrees C
      and then activities of phosphorolytic and glucosidic enzymes were assayed in
      liver, heart, brain, and red and white skeletal muscle, and compared with aerobic
      controls. In vitro incubations also assessed protein kinase A control of
      phosphorolytic enzymes. A functional enzyme cascade system for the activation of
      glycogen phosphorylase was found in all organs, and both phosphorylase and
      phosphorylase kinase were stimulated by in vitro incubation with the catalytic
      subunit of cAMP-dependent protein kinase. Anoxic submergence led to significant
      increases in phosphorylase activities in liver and heart (phosphorylase a rose 2-
      and 2.5-fold, respectively) but phosphorylase kinase and protein kinase A
      activities in liver were reduced after 5 hr exposure. Both acidic (pH 4) and
      neutral (pH 7) forms of alpha-glucosidase were detected in all five organs with
      highest activities in liver. Activity of acid alpha-glucosidase, which degrades
      lysosomal glycogen, increased by 2-fold in liver during anoxic submergence. The
      data show that glycogen breakdown in turtle liver during anoxic submergence may
      result from coordinated activations of both the cytoplasmic phosphorolytic and
      the lysosomal glucosidic pathways of glycogenolysis.

PMID- 7584613
TI  - Detection of mutagen specific adduct formation in DNA using sequencing
      methodology.
AB  - It has been reported that single stranded viral DNA reacts with the carcinogen,
      chloroacetaldehyde at specific hot spots (Premaratne et al., 1993 Int. J.
      Biochem. 25, 1669-1672). We tested this occurrence with several other mutagens
      and potential carcinogens. A series of chemicals (chloroacetaldehyde, methyl,
      ethyl, and propyl nitro nitrosoguanidine, hydrazine, 2,4 dinitrophenyl hydrazine,
      hydroxylamine and methyl methanesulfonate) were each separately reacted with
      viral M13mp18 DNA for 2 hr at 37 degrees C and pH 4.9. The locations of adduction
      were identified as points of chain termination (or polymerase fall off) when the
      reacted DNA was subjected to a modified sequencing procedure that had ample
      regular labeled and unlabeled nucleotides but lacked dideoxy chain termination
      mixtures. Chain termination was observed to occur at specific, non-random, sites
      rather than with equal probability at all bases of the DNA. Chemicals with
      similar structures had identical points of "fall off". The pattern of chain
      termination appears to be unique to each class of compounds and is independent of
      temperature, pH, and salt concentration. Termination is believed to occur when
      the DNA polymerase encounters an adduct. Mutagens of different unrelated
      structures when reacted with this DNA produced different sites of adduct
      formation, while the alkyl nitro nitrosoguanidines, compounds with homologous
      structure showed identical points of chain termination.

PMID- 7584622
TI  - Regulation of the DNA binding activity of NF-kappa B.
AB  - The DNA binding activity of the dimeric sequence-specific transcription factor NF
      kappa B can be controlled by a variety of post-translational mechanisms,
      including interactions with inhibitor proteins and by its redox state. The NF
      kappa B family of transcription factors bind to kappa B motif sequences found in
      promoter and enhancer regions of a wide range of cellular and viral genes.
      Normally NF-kappa B family proteins are held in the cytoplasm in an inactive, non
      DNA binding form by labile I kappa B inhibitor proteins. When the cell is
      activated by one of a wide range of stimuli, typically those associated with the
      cellular response to pathogens or stress, proteolytic degradation of I kappa B
      inhibitor proteins allows active NF-kappa B to translocate to the nucleus where
      it activates transcription of responsive genes. The initial trigger for I kappa B
      degradation is a signal-induced site-specific phosphorylation by an as yet
      unidentified kinase, which appears to target I kappa B for the covalent addition
      of multiple copies of the ubiquitin polypeptide. This modification subsequently
      allows the proteolytic degradation of the ubiquitinated I kappa B by the cellular
      26S multicatalytic proteinase (proteasome) complex. It was recently shown that
      increased I kappa B-alpha expression in the cytoplasm leads to I kappa B-alpha
      accumulating in the nuclear compartment, removing template-bound NF-kappa B, and
      reducing NF-kappa B-dependent transcription. These NF-kappa B-I kappa B-alpha
      complexes could then be actively re-exported to the cytoplasm, allowing the cell
      to respond to further stimuli.

PMID- 7584621
TI  - Purification and characterization of a lectin from the seeds of Erythrina
      costaricensis.
AB  - This work compares three methods used for the purification of the lectin of
      Erythrina costaricensis and presents new data regarding its physicochemical
      properties and N-terminal sequence. The lectin was isolated from the seeds of
      Erythrina costaricensis using O-alpha-D galactosyl polyacrylamide, galactose
      derivatized Sepharose and ConA-Sepharose as affinity chromatography supports. The
      lectin content is about 110 mg/100 g dry flour. The protein agglutinates human
      and rabbit erythrocytes; other animal erythrocytes were not agglutinated. The
      agglutination is inhibited by galactosyl moieties, p-nitrophenyl-beta-galactoside
      being the strongest inhibitor. The lectin is a dimeric protein (56 kDa) with
      identical subunits, each with a mol. wt of 27.2 kDa. The lectin is a glycoprotein
      with 3.6% neutral sugars. The amino acid content shows a high proportion of
      acidic and hydroxy residues; cysteine is absent and there are 6 methionines/mol
      protein. The N-terminal sequence is similar to those of Erythrina lectins; Ala is
      the N-terminal amino acid. In summary this paper reports the isolation of a
      lectin which shares many structural and functional properties with other
      Erythrina lectins. However, differences in some of its characteristics (pI,
      interactions with animal erythrocytes, mitogenic ability) indicate some
      distinctions in structure amongst this group of proteins.

PMID- 7584619
TI  - Optimized bacterial production of nonglycosylated human transferrin and its half
      molecules.
AB  - Transferrin is a glycoprotein functioning in iron transport in higher eukaryotes,
      and consists of two highly homologous domains. To study the function of the
      glycan residues attached exclusively to the C-terminal domain, we have
      constructed a plasmid allowing production of nonglycosylated human transferrin in
      Escherichia coli. By molecular biological and genetic techniques, production was
      stepped up to 60 mg/l. Similar plasmids were constructed for production of the
      two half-transferrins. The recombinant proteins accumulate in inclusion-body-like
      aggregates, where they appear to bind iron without causing bacteriostasis.
      Proteins active in iron binding have been purified from these inclusion bodies.

PMID- 7584620
TI  - Polyamine uptake by a rodent filariid, Acanthocheilonema viteae (Nematoda:
      Filarioidea).
AB  - Helminth parasites lack the capacity to synthesize polyamines de novo. With the
      view to characterise alternative pools for the replenishment of polyamines,
      uptake of spermidine and spermine, were studied in Acanthocheilonema viteae, a
      parasite known to infect rodents. Motile worms recovered from the subcutaneous
      tissues of experimentally infected Mastomys natalensis were incubated in vitro
      with radiolabelled polyamines for the uptake assays. A time-dependent,
      temperature-sensitive, energy-requiring and saturable-uptake of the polyamines
      was observed. Male worms exhibited better uptake than the females and spermidine
      influx occurred at a higher rate than for spermine. A marginal competition of
      spermine with spermidine uptake and vice-versa was noticed while putrescine did
      not compete with uptake of either polyamines. Methyl-glyoxal-bis-guanyl hydrazone
      and Berenil caused significant inhibition of spermidine as well as spermine
      uptake. Subcutaneous tissues of A. viteae infected animals exhibited markedly
      higher levels of polyamines compared with the tissues obtained from healthy
      animals. Filarial worms are thus equipped with multiple polyamine transport
      systems which may aid their growth and survival within the host.

PMID- 7584618
TI  - Enzymatic reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) by lysate of rat
      liver mitochondria.
AB  - The oxidation of mitochondrial sulphydryl groups is known to increase the
      permeability of mitochondrial membranes and to be a key event in oxidative
      stress. Resistance to this damage is thought to involve thioredoxin reductase. In
      this study, the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) by a
      lysate of rat liver mitochondria was used to assay the mitochondrial disulphide
      reducing capacity. NADPH-dependent reduction of DTNB was used to distinguish
      enzymatic reduction from the non-enzymatic reduction. Enzymatic reduction by the
      mitochondrial lysate was suppressed by DTNB at concentrations exceeding 0.25 mM
      and by pH above 7.0. It was strongly inhibited by Zn2+ and Mn2+ (IC50 about 2.5
      and 20 microM, respectively) and was more weakly inhibited by Mg2+ and Ca2+ (IC50
      about 1.8 and 2.1 mM, respectively). As a consequence of inhibition by divalent
      cations, the reaction was stimulated by both physiological (ATP, ADP,
      pyrophosphate and citrate) and non-physiological (EDTA and EGTA) chelators.
      Reduction of insulin disulphides by the mitochondrial lysate was dependent on the
      presence of a divalent cation chelator during the isolation of mitochondria and
      during the enzyme assay. Our results suggest that stimulation of mitochondrial
      disulphide reducing activity by lowered pH, as well as by increased levels of
      ATP, ADP and citrate, has the potential to contribute to the maintenance of
      mitochondrial sulphydryl groups under oxidative conditions.

PMID- 7584623
TI  - A study of a synaptosomal thyrotropin releasing hormone-inactivating
      pyroglutamate aminopeptidase from bovine brain.
AB  - Pyroglutamate aminopeptidase type II is a highly specific membrane-bound
      neuropeptidase that has the ability to remove N-terminal pyroglutamate (Glp) from
      Thyrotropin Releasing Hormone (Glp-His-Pro-NH2) or very closely related
      tripeptides or tripeptide amides. In this paper we report on the purification and
      characterisation of a pyroglutamate aminopeptidase activity from the synaptosomal
      membranes of bovine brain. The Triton X-100 solubilised enzyme was purified
      nearly 600-fold by a combination of conventional column chromatography steps with
      a recovery/yield of 17.0%. Phase-partitioning experiments with Triton X-114
      showed the activity to be an integral membrane protein. This detergent
      solubilised pyroglutamate aminopeptidase activity was found to have a relative
      molecular mass of 240 kDa on a calibrated S-200 column. HPLC analysis on a C18
      reverse-phase column showed that the purified activity displayed a very narrow
      substrate specificity cleaving only Thyrotropin Releasing Hormone (TRH) or the
      very closely related acid-TRH, LHRH (1-3) and the TRH-analogue (methyl-His)-TRH
      and had a Km of 100 microM for the fluorimetric substrate Glp-His-Pro-methyl
      coumarin. The enzyme was inactivated by the metalchelator 1,10-ortho
      phenanthroline but showed less sensitivity to EDTA. It also showed some
      inhibition by thiol protease inhibitors such as iodoacetate and n-ethyl
      maleimide. In summary, we have purified a pyroglutamate aminopeptidase from the
      synaptosomal membrane of bovine brain. This enzyme displays characteristics
      consistent with it being classified as a PAP type II neuropeptidase with only
      minor differences from other proteases in this group.

PMID- 7584624
TI  - Biotinylated aprotinin: a versatile probe for the detection of serine proteinases
      on western blots.
AB  - The present study was undertaken to provide a highly sensitive detection system
      for the identification and characterisation of serine proteinases separated by
      sodium dodecyl sulphate polyacrylamide gel electrophoresis. Biotinylated
      aprotinin of high specific activity (88-92% active) was prepared (i) by reaction
      of aprotinin directly with N-hydroxy sulfosuccinimidyl-6-(biotinamido) hexanoate,
      and (ii) by reaction of aprotinin-trypsin complex with N-hydroxy
      succinimidobiotin. Both biotinylated aprotinin samples were suitable as probes
      for the detection of the serine proteinases, neutrophil elastase and cathepsin G,
      pancreatic trypsin and chymotrypsin and plasmin on nitrocellulose blots. Specific
      irreversible chloromethyl ketone proteinase inhibitors used in combination with
      this detection system enabled respective proteinases to be selectively
      inactivated and thus positively identified. The biotinylated aprotinin detection
      system was highly sensitive and could detect as little as 0.2 ng (8.5 fmol) of
      active proteinase (trypsin). In summary, a method has been developed for the
      sensitive detection of serine proteinases separated by SDS-PAGE. The method is
      more sensitive and convenient to perform than conventional zymography and
      significantly, when used in conjunction with specific serine proteinase
      inhibitors or specific antibodies can yield appreciable information on the
      identity of the respective serine proteinases being examined. Furthermore the
      molecular mass of the serine proteinase may be reliably obtained by this method.
      This method should find application in identifying the role that serine
      proteinases play in the etiopathogenesis of connective tissue disorders.

PMID- 7584625
TI  - NADP-malate dehydrogenase activity in rat erythrocytes. Comparison with pyruvate
      kinase in relation to coupling with lactate dehydrogenase.
AB  - The present study explores the possible channelling of pyruvate generated by
      either pyruvate kinase or NADP-malate dehydrogenase to lactate dehydrogenase in
      cross-linked and permeabilized erythrocytes. The generation of both unlabelled
      and 14C-labelled pyruvate and lactate was measured in rat erythrocytes, which
      were prepared for cross-linking with dimethyl suberimidate and permeabilization
      by digitonin and then exposed to unlabelled or 14C-labelled malate and/or phospho
      enol-pyruvate. Rat erythrocytes were found to display NADP-malate dehydrogenase
      activity. Under conditions in which the generation rates of pyruvate from either
      phospho-enol-pyruvate (15 microM) or malate (0.5 mM) were not vastly different
      from one another, a greater fraction of the 2-keto acid was converted to lactate
      when produced from phospho-enol-[1-14C]pyruvate rather than [U-14C]malate. This
      difference was most obvious when the availability of exogenous NADH was close to
      or somewhat below that theoretically required to ensure full conversion of
      endogenously formed pyruvate to lactate. These findings are compatible with the
      view that pyruvate generated at the pyruvate kinase level is converted to lactate
      more efficiently than pyruvate produced in the reaction catalysed by NADP-malate
      dehydrogenase.

PMID- 7584629
TI  - Absence of circadian variations in urinary porphyrin excretion in normal
      subjects.
AB  - The hypothesis that urinary porphyrins could be excreted in a circadian rhythm
      was examined. A group of 20 healthy subjects, 10 males and 10 females, aged 20-40
      years, were used in this study. Urine was collected at 4-hr intervals over three
      24-hr periods. Median porphyrin concentrations (microgram l-1 or microgram g-1 of
      creatinine) were similar in the six groups, but significant differences were
      observed in that excreted. Highest porphyrin excretion was detected in the
      afternoon (12.00-16.00 hr) and, in the evening (16.00-20.00 hr). pH values were
      also increased at evening but did not correlate with porphyrin excretion. Despite
      these temporal variations, no cycles indicating circadian periodicity were
      observed. Therefore, a 24-hr collection of urine is not necessary for the initial
      evaluation of porphyrin metabolism.

PMID- 7584627
TI  - Modification of kinetic parameters of glycogen phosphorylase from mantle tissue
      of Mytilus galloprovincialis by a phosphorylation mechanism.
AB  - Initial rate and affinity studies on mantle Mytilus phosphorylase a were carried
      out in order to find possible differences in its kinetic properties with respect
      to phosphorylase b. Phosphorylase a was not stimulated for any AMP
      concentrations. Michaelis constants (Km) are 0.05 mg/ml glycogen, 1.15 mM
      inorganic phosphate and 1.50 mM glucose-1-phosphate. The Kms for the substrates,
      in the direction of glycogen breakdown, are enhanced by non-saturating
      concentrations of cosubstrate, without reducing the apparent maximum velocity.
      First order and hyperbolic kinetics and values of the allosteric constant smaller
      than 2 were observed. These results suggest a catalytic mechanism different to
      that shown for mantle Mytilus phosphorylase b.

PMID- 7584626
TI  - Caffeine inhibition of glycogen phosphorylase from Mytilus galloprovincialis
      mantle tissue.
AB  - A different caffeine inhibition of both phosphorylated and unphosphorylated forms
      of glycogen phosphorylase from Mytilus mantle has been demonstrated. Caffeine
      increases the allosteric constant of phosphorylase b 30-fold, acting as an
      allosteric inhibitor (nH = 2) of mixed type with respect to inorganic phosphate
      (Pi) and AMP, and of single competitive type with respect to glycogen. The
      Mytilus phosphorylated form is also caffeine inhibited through competitive
      inhibition in relation to Pi and glycogen. In this case, the inhibitor does not
      modify the allosteric constant (near 2), neither does it display allosteric
      effects (nH = 1). The results demonstrate the notable modification of the
      nucleotide site promoted by the phosphorylation process and the existence of a
      functional inhibitory nucleoside site in Mytilus phosphorylase.

PMID- 7584628
TI  - Antioxidant enzyme activities and lipid peroxidation levels in exercised and
      hypertensive rat tissues.
AB  - Previous studies have shown that exercise-induced changes in muscle antioxidant
      status occur shortly after exercise. The present studies were designed to
      determine if longer-term exercise-related changes in antioxidant enzyme
      activities in both normotensive (WKY) and hypertensive rats (SHR) occurred, and
      if these changes were related to the levels of lipid peroxidation. WKY and SHR
      rats were exercised over a 10-week period using a progressive treadmill regimen.
      After a 1-week detraining period, the animals were euthanized and measurements of
      tissue antioxidant enzyme activities and lipid peroxide levels were determined in
      both exercised and cage-sedentary groups. Decreases in antioxidant activities
      (particularly glutathione peroxidase and catalase) in liver, kidney, skeletal and
      cardiac were associated with exercise training in both WKy and SHR rats (e.g.
      left ventricular glutathione peroxidase specific activity in WKY rats was
      decreased from 234 +/- 25 [SD, n = 12] to 187 +/- 17 [SD, n = 11] units/mg
      protein). Elevations in activities of antioxidant enzymes were generally
      associated with hypertension in these tissues (e.g. left ventricular glutathione
      peroxidase specific activity in SHR rats was 275 +/- 30 [SD, n = 12] units/mg
      protein), but changes in activities were more variable than those seen in
      response to exercise. Exercise-related changes in tissue levels of thiobarbituric
      acid-reactive substances (an indirect measure of tissue lipid peroxide levels)
      generally did not correlate with exercise-related antioxidant enzyme activity
      changes, and hypertension had no effect on these levels except in liver.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584631
TI  - Leishmania donovani: cellular control of ornithine decarboxylase in
      promastigotes.
AB  - Ornithine decarboxylase, a key enzyme in polyamine biosynthesis, is essential for
      normal cell growth and proliferation. Furthermore, the inhibition of this enzyme
      is a potential way of controlling such growth. In order to shed light on the role
      of ornithine decarboxylase in regulation of Leishmania growth we examined the
      activity of this enzyme during the life cycle of these organisms. Exponentially
      growing Leishmania promastigotes were resuspended at a density of 3 x 10(6)
      cells/ml. 2 x 10(7) cells were withdrawn 24 hr later at different time intervals
      for induction studies and ornithine decarboxylase activity was measured.
      Ornithine decarboxylase showed a growth related pattern in L. donovani
      promastigotes. Induction studies showed that ornithine decarboxylase activity
      rapidly increased in late log phase cells when resuspended in fresh medium. A
      biphasic induction curve was observed similar to that observed in mammalian
      cells. The first peak was observed at 6 hr and the second at 16 hr. Cycloheximide
      and Actinomycin D inhibited induction at 16 hr by 65-68%. Polyamines at a level
      not inhibitory to growth (10 microM) inhibited ornithine decarboxylase induction
      by 30-40% late in the induction period. Putrescine and spermidine both inhibited
      the first peak of induction. Putrescine suppressed ornithine decarboxylase
      activity by 39% at 16 hr whereas spermidine by only 29%. The half life of
      ornithine decarboxylase in promastigote forms grown in the presence of
      cycloheximide was >6 hr. These studies indicate that although the Leishmanial
      ornithine decarboxylase follows a similar induction pattern to that previously
      reported in the mammalian cells, it is less susceptible to exogenous polyamines
      and is comparatively stable. This lack of ornithine decarboxylase regulation and
      turnover may be exploitable in the development of various therapeutic agents to
      inhibit Leishmanial growth.

PMID- 7584630
TI  - Age-related alterations in collagen and total protein metabolism determined in
      cultured rat dermal fibroblasts: age-related trends parallel those observed in
      rat skin in vivo.
AB  - The cultured fibroblast has been extensively used as a model system to study
      aging. However, few studies have examined the veracity of observations obtained
      in cultured fibroblasts aged in vitro to those made in animal tissues in vivo.
      This paper compares age-related alterations in collagen metabolism measured in
      cultured cells with previously reported results in the aging rat (Mays et al.
      (1991) Biochem. J. 276, 307-313). Age-related changes in collagen synthesis in
      rat skin fibroblasts in vitro over 30 population doublings were determined based
      on the production of hydroxy-[14C]proline. Degradation of newly synthesized
      collagen was based on the appearance of free hydroxy-[14C]proline in the culture
      system. Total protein synthesis rates were based on the incorporation of
      [14C]proline into proteins. In vitro rates of collagen synthesis decreased 5-fold
      over 30 population doublings (P < 0.05). Degradation of newly synthesized
      collagen increased from 33.0 +/- 0.8% (n = 4, SEM) to 45.2 +/- 1.1% (n = 4; P <
      0.05) over the same period, with a maximum after 25 population doublings of 55.8
      +/- 1.1% (n = 4). Total protein synthesis rates decreased by one-half over 30
      population doublings (P < 0.05). The results indicated that collagen production
      decreased as cells aged in vitro and that this was due to both changes in
      synthesis and degradation. The results demonstrate that age-related alterations
      in collagen and total protein metabolism of skin fibroblasts in culture were
      similar to those reported previously for skin in vivo, suggesting that for
      studies of these processes, fibroblasts in culture provide an appropriate model.

PMID- 7584635
TI  - Acknowledging expert practice.

PMID- 7584632
TI  - Kinetics for the inhibition of acetylcholinesterase from human erythrocyte by
      cisplatin.
AB  - The antitumor drug cisplatin causes neurological side-effects in patients treated
      with this drug. Since acetylcholine plays a key role in human neurotransmission
      we characterized the inhibitory effect of cisplatin on the enzyme,
      acetylcholinesterase. Enzyme activity was monitored spectrophotometrically using
      Ellman's method. The time for 50% inhibition (t1/2) was inversely proportional to
      the concentration of the cisplatin. The reaction was therefore assessed to have a
      bimolecular rate constant of 36.5 (mM min)-1. The Km and Vmax were both decreased
      by 45 and 48%, respectively by 7.0 mM cisplatin during the reversible phase while
      the Km was increased 138% and Vmax was decreased up to 65% in the irreversible
      phase. The nature of the inhibition was uncompetitive and complex irreversible at
      the reversible and irreversible stages respectively. The inhibition constants for
      reversible and irreversible steps were estimated as 1.12 mM and 97.70 (mM min)-1
      respectively. The dissociation constant for the irreversible complex was 2.62 mM.
      These studies show that cisplatin is an uncompetitive inhibitor of
      acetylcholinesterase. Such effects may contribute, at least in part, to the
      neurotoxic effects associated with the use of cisplatin.

PMID- 7584634
TI  - Heterogeneous responses to an intravenous glucose load.
AB  - The aim of this study was to determine how the insulin sensitive enzymes pyruvate
      dehydrogenase (PDH) complex and glycogen synthase (GS) of different tissues
      respond to an endogenous pulse of insulin elicited by an intravenous infusion of
      glucose. An infusion of glucose (0.5 g/kg) into conscious, unrestrained animals
      via an indwelling cannula rapidly elevated plasma insulin concentration (to
      approx. 600 microU/ml after 10 min). The animals were sacrificed at selected time
      points after the commencement of infusion. Samples of heart, red quadriceps
      muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) were excised
      and assayed for PDH complex and GS activities. The glucose infusion elicited a
      rapid (< 5-10 min) increase in both PDH complex and GS activities in heart, BAT
      and WAT. The maximum rise in the activity of PDH and GS above basal were
      (respectively) 2- and 8-fold for heart, 5.5- and 5-fold for BAT, and 3.5- and 4
      fold for WAT. The return of PDH complex activity to basal values was also very
      rapid (occurring over the next 20 min). The glucose infusion also stimulated GS
      activity in red quadriceps muscle but was, however without effect on PDH complex
      activity in this tissue. We conclude that although insulin stimulates PDH and GS
      with the same time course and magnitude in many insulin sensitive tissues, the
      time course and magnitude of insulin stimulation of these enzymes can vary
      between tissues. These results may mean that the stimulation of PDH complex and
      GS by insulin occurs via different receptor-effector pathways.

PMID- 7584633
TI  - Ribonuclease inhibitors in human blood: comparative studies on the inhibitors
      detected in erythrocytes, platelets, mononuclear leukocytes and granulocytes.
AB  - The erythrocyte ribonuclease inhibitor (RI) and platelet RI were separately
      purified to homogeneity and showed similar properties to those of human brain and
      placental RIs. The same type of RI seemed to be present in mononuclear leukocytes
      and granulocytes. The RI contents of these cells were detectable by immunoblot
      analysis using anti-human placental RI antibody. Neither RI activity nor the
      molecule cross-reactive with the anti-human placental RI antibody was detectable
      in any plasma sample. It is intriguing to detect active RI in mature
      erythrocytes, where no nucleus exists and RNA metabolism is unlikely to occur.

PMID- 7584636
TI  - Fewer nurses means poorer care.

PMID- 7584638
TI  - Future career directions. Interview by Teresa O'Connor.

PMID- 7584639
TI  - Getting to grips with the code.

PMID- 7584637
TI  - Promoting night shift.

PMID- 7584640
TI  - Promoting a Maori voice. Interview by Teresa O'Connor.

PMID- 7584641
TI  - Who owns patients' files?

PMID- 7584642
TI  - Nursing overseas. Island nursing brings rewards.

PMID- 7584643
TI  - Nursing people in their own homes. Interview by Anne Manchester.

PMID- 7584644
TI  - NZNO conference. Conference to empower nurses.

PMID- 7584645
TI  - Trusting the team.

PMID- 7584646
TI  - Reforms round-up. Freedom to care.

PMID- 7584647
TI  - Changing the face of health service providers.

PMID- 7584648
TI  - Public health--a service to be saved.

PMID- 7584649
TI  - True stories.

PMID- 7584651
TI  - Helping families the healthy way.

PMID- 7584650
TI  - The battle for health services.

PMID- 7584652
TI  - Colon cleansing at home.

PMID- 7584653
TI  - Bringing healing through touch. Interview by Anne Manchester.

PMID- 7584654
TI  - Beating bad backs.

PMID- 7584655
TI  - A way of seeing.

PMID- 7584656
TI  - The management of leg ulcers in a patient with ulcerative colitis. This case
      study details the treatment of a patient with pyoderma gangrenosum on the shins
      of both legs.
AB  - Pyoderma gangrenosum is a rare condition which is sometimes associated with
      ulcerative colitis and Crohn's disease. The pathological basis is not completely
      understood but it may be caused by vasculitis. The lesions are typically said to
      have purple overhanging edges and a necrotic base. The condition may also occur
      with rheumatoid arthritis, multiple myeloma and leukaemia. The treatment of
      choice is systemic steroids but it may also respond to azathioprine, minocycline
      or clofazimine.

PMID- 7584657
TI  - The cost of wound care in the community. Part two in a series of three articles
      discusses the expenditure on wound management materials.
AB  - As part of a project examining expenditure on all wound management materials
      currently prescribed by general practitioners in Wales, the cost of dressing
      packs, pharmaceutical preparations and surgical absorbents was analysed. The
      findings suggest that by replacing non-woven swabs for woven swabs and by
      discontinuing the use of topical antibiotic powders and multiple dressing packs,
      considerable savings can be made.

PMID- 7584659
TI  - Leg ulcer odour detection identifies beta-haemolytic streptococcal infection.
AB  - beta-Haemolytic streptococci were identified in bacteriological cultures from 14
      of 24 chronic venous leg ulcers in 21 patients. Multi-element odour detection
      (MEOD) analysis demonstrated a significant difference in odour in those ulcers
      from which beta-haemolytic streptococci were isolated (p < 0.01). MEOD has
      potential to detect pathogenic organisms instantaneously in the clinical setting.

PMID- 7584660
TI  - Mattresses and beds. A guide to systems available for relieving and reducing
      pressure.

PMID- 7584658
TI  - Granulocyte monocyte-colony stimulating factor as an agent for wound healing. A
      study evaluating the use of local injections of a genetically engineered growth
      factor in the management of wounds with a poor healing prognosis.

PMID- 7584661
TI  - A contemporary approach to wound care education. Education must enable the
      practitioner to replace traditional and out-dated practices in wound care with
      research-based practice.

PMID- 7584662
TI  - Wound healing and the role of the podiatrist.A discussion of the rule of the wide
      range of foot disorders diagnosed and managed by the podiatrist.

PMID- 7584663
TI  - Review of classic research: Control of scarring.

PMID- 7584665
TI  - Characterization of a domain of a human type I interferon receptor protein
      involved in ligand binding.
AB  - Two monoclonal antibodies that recognize different epitopes of the extracellular
      domain of one of the proteins that constitute the type I interferon receptor were
      used to delineate the interferon binding site. Antibody 64G12 both inhibits the
      binding of radiolabeled interferon-alpha 2 and IFN-alpha 8 to their cell surface
      receptors and neutralizes the antiviral and antiproliferative actions of all the
      type I interferons tested, including IFN-beta, IFN-omega, and human leukocyte
      IFN, a mixture of different interferon-alpha isotypes. Antibody 34F10 recognizes
      the type I interferon receptor with an affinity similar to that of the MAb 64G12
      but does not inhibit either the binding or the biologic activity of any of the
      type I interferons tested. Both antibodies recognize a protein of 105 +/- 5 kD
      from either Daudi or Ly28 cells. Immunoprecipitation following surface iodination
      demonstrated that the neutralizing MAb recognizes a protein of 105 kD and the
      nonneutralizing MAb a protein of 110 kD in extracts of Daudi cells. A second less
      intense band was also detected by both antibodies. Cross-linking of IFN-alpha 2
      to its receptor before immunoprecipitation prevented the neutralizing antibody
      from immunoprecipitating the receptor protein, but the nonneutralizing MAb was
      still able to recognize a 140 kD protein corresponding to the cross-linked
      interferon-receptor protein complex. Thus, an interferon binding domain appears
      to be localized in a region between amino acids 23 and 229 of the extracellular
      domain of a transmembrane protein that forms part of the type I interferon
      receptor complex containing the epitopes recognized by each antibody.

PMID- 7584664
TI  - A monoclonal antibody to the NH2-terminal region of human interferon-gamma
      inhibits its antiproliferative activity without affecting its internalization.
AB  - MAb IGMB-15, an anti-hIFN-gamma MAb, neutralizes the antiproliferative activity
      of hIFN-gamma without affecting that of hIFN-alpha or hIFN-beta. The neutralizing
      capacity of MAb IGMB-15 is wide: it has been assessed on cell lines whose origin
      and sensitivity to hIFN-gamma differ. The binding of hIFN-gamma to its receptor
      and its subsequent internalization into the target cell were not influenced by
      the antibody. MAb IGMB-15 has been found to interact with hIFN-gamma in solution
      but not when the lymphokine was associated with its cell surface receptor,
      showing that the growth of certain cell lines can be inhibited at the cell
      membrane level. This finding is consistent with the existence of an accessory
      factor responsible for the antiproliferative activity of hIFN-gamma.

PMID- 7584666
TI  - Potential for interferon-alpha-based therapy in mesothelioma: assessment in a
      murine model.
AB  - Malignant mesothelioma is an aggressive tumor, usually induced by asbestos
      exposure, that has a poor prognosis and is unresponsive to conventional therapy.
      The present study was aimed at assessing the potential for interferon-alpha (IFN
      alpha)-based therapies in a murine model for malignant mesothelioma. The effect
      of recombinant human IFN-alpha B/D on tumor growth, alone and in combination with
      either of two immunomodulatory and antiproliferative agents beta-carotene or
      alpha-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN
      alpha treatment is most efficacious when commenced early in tumor development.
      Combination of IFN-alpha with either DFMO or dietary beta-carotene
      supplementation improved the effect of an otherwise suboptimal IFN-alpha therapy
      regimen. Both IFN-alpha and beta-carotene had in vivo stimulatory effects on
      immune cells, perhaps indirectly by inhibiting TGF-beta generation. The
      immunomodulatory effects may contribute, at least in part, to the positive
      antitumor and clinical activities of the treatments in this model.

PMID- 7584668
TI  - Comparison of the in vitro host range of recombinant met-interferon-con1,
      interferon-alpha 2b, and interferon-beta [corrected].
AB  - The antiviral activity of human r-metIFN-con1 was compared with that of IFN-alpha
      2b and IFN-beta on a number of human, other primate, rodent, feline, and canine
      cell lines. Although the specific activities of r-metIFN-con1 and IFN-alpha 2b
      differed 10-fold, the host range was very similar. The host range of IFN-beta
      differed from that of r-metIFN-con1 and IFN-alpha 2b in that Vero cells were 100
      fold better protected by IFN-beta and MDBK protected at a 100-fold less
      efficiency. In general, there were only minor differences between the host ranges
      of the three interferons, human and primate cells being better protected than
      those of other species. However, the tissue of origin of the cell appears to be
      more important than the species of origin in defining host range [corrected].

PMID- 7584667
TI  - Pulmonary catabolism of interferon-gamma evaluated by lung perfusion of both
      normal and smoke-exposed rats.
AB  - The role of the lungs in the catabolism of rat recombinant interferon-gamma,
      either in normal rats or in rats subjected to an acute cigarette smoking episode,
      was evaluated using an isolated and perfused lung preparation. After
      administration of interferon-gamma into the lung perfusion medium, there was no
      clearance of the cytokine in either control or smoke-exposed rat lungs, and only
      0.1 +/- 0.2% of the total dose was recovered in the bronchoalveolar lavage fluid.
      When the same amount of interferon-gamma was instilled into the bronchial
      alveolar tree, concentrations of the cytokine in the perfusate increased
      progressively so that after 3 h up to 71.2 +/- 4.3 and 62 +/- 5.7% of the
      administered dose, as measured by ELISA test, had been transferred from the
      bronchial lumen to the perfusion medium of either control or smoke-exposed rat
      lungs, respectively, the latter values being significantly lower (p < or = 0.05)
      than those obtained in control lungs. Moreover, total recoveries of interferon
      gamma evaluated in smoke-exposed rat lungs (78.4 +/- 8.6%) were also
      significantly lower than those observed in control rat lungs (91.4 +/- 11.8%).
      Biologic activity evaluations on the same samples gave values significantly lower
      than those obtained using ELISA, indicating a partial loss of biologic activity
      during transalveolar transit. In conclusion, it appears that the transfer of
      interferon-gamma is almost exclusively unidirectional from the alveolar space to
      the plasmatic pool, with partial degradation during transalveolar passage.

PMID- 7584669
TI  - Normal mouse skin lymphocyte, Langerhans cell, and keratinocyte responses to
      intradermal injections of interferon-alpha and interferon-gamma.
AB  - To investigate the skin immune responses induced by intradermal injections of
      interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), normal C3H mice
      were injected intradermally with murine recombinant interferon-alpha (rIFN
      alpha), interferon-gamma (rIFN-gamma), or the combination of rIFN-alpha and rIFN
      gamma, three times per week for 2 or 4 weeks. Contralateral sites were similarly
      injected with placebo (saline). The results showed that after 6 or 12 injections
      of rIFN-alpha (10,000 IU/per injection), epidermal ATPase+ and Ia+ Langerhans
      cells (LGs) decreased significantly (p < 0.01 and p < 0.05) but dermal
      lymphocytic infiltrates, including CD3+ (pan-T cells), L3T4+ (T helper cells),
      Lyt-2+ (T suppressor/cytotoxic cells), MOMA+ (macrophages and monocytes), and
      dermal Ia+ cells, increased significantly (p < 0.01) compared with both saline
      injection sites and untreated skin. In contrast to rIFN-alpha, 6 injections of
      10,000 IU rIFN-gamma failed to induce significant changes in either epidermal LGs
      or dermal lymphocytic infiltrates, except for an increase in dermal MOMA+ cells.
      High-dose rIFN-gamma injections (50,000 IU) strongly enhanced the expression of
      Ia antigen in epidermal keratinocytes (KCs), increased dermal lymphocytic
      infiltrates, and decreased the LGs in a similar pattern to that of rIFN-alpha.
      Furthermore, rIFN-gamma (50,000 IU) injections induced Ia antigen expression on
      the KCs in the contralateral saline injection areas, suggesting a systemic
      effect. Injections of a combination of rIFN-alpha and rIFN-gamma failed to show
      synergism for induction of skin immune responses.

PMID- 7584670
TI  - A synthetic inhibitor of interleukin-1 beta converting enzyme prevents endotoxin
      induced interleukin-1 beta production in vitro and in vivo.
AB  - A potent, reversible, tetrapeptide inhibitor of interleukin-1 beta converting
      enzyme (ICE), L-709,049, has been shown to suppress the in vitro production of
      mature IL-1 beta. We now report that this inhibitor also effectively suppresses
      the production of mature IL-1 beta in a murine model of endotoxic shock.
      Intraperitoneal administration of L-709,049 reduced the elevations of IL-1 beta
      in the plasma and peritoneal fluid of mice treated with LPS in a dose-related
      manner (ED50 = 2 +/- 0.9 mg/kg). LPS-induced elevations in IL-1 alpha and IL-6 in
      these mice were unaffected, indicating that the inhibitor specifically affected
      IL-1 beta production. Immunoblot analysis of plasma and peritoneal fluid
      indicated that L-709,049 suppressed the formation of mature IL-1 beta production
      in vivo. When mouse blood was incubated in vitro with LPS, IL-1 beta was released
      into the plasma. This assay was used to determine ex vivo the activity of an ICE
      inhibitor in the blood following its administration to mice. Blood obtained 15
      minutes after ip administration of 10 mg/kg of L-709,049 to mice produced 80%
      less IL-1 beta than control blood, and IL-1 beta production returned to control
      levels in blood obtained 30 minutes after injection of this inhibitor. In
      addition, the capacity of the blood plasma obtained from these animals to prevent
      the cleavage of a synthetic substrate by ICE disappeared within 1 h of ip
      administration of 50 mg/kg of inhibitor.

PMID- 7584671
TI  - In vivo administration of granulocyte-macrophage colony-stimulating factor and
      granulocyte colony-stimulating factor increases neutrophil oxidative burst
      activity.
AB  - The influence of CSF therapy on the superoxide (O2-) releasing capacity in
      response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) of neutrophils from 32
      patients with testicular cancer receiving high-dose chemotherapy followed by
      autologous bone marrow transplantation (ABMT) was assessed: 8 patients were
      treated as control group without CSF therapy, 12 patients received GM-CSF, and 12
      patients received G-CSF. To monitor the kinetics of the respiratory burst,
      leukocytes were collected before initiation of chemotherapy and ABMT, during CSF
      administration on days 1 and 3 after leukocyte recovery, and 7 days after
      leukocyte recovery (controls) or 3 days after the end of CSF therapy. Neutrophils
      from patients who received GM-CSF showed a significantly higher superoxide anion
      release compared with control patients (p < 0.001). O2- production in these
      patients was higher than that achieved by in vitro preincubation of neutrophils
      from control patients. Increased burst activity was seen only during infusion of
      GM-CSF and returned to pretherapeutic values after the end of GM-CSF
      administration. A similar but less pronounced increase was seen in patients who
      received G-CSF. In vitro preincubation of neutrophils from the same patients with
      GM-CSF, G-CSF, or TNF showed that O2- production by neutrophils from patients
      receiving GM-CSF could not be further enhanced, whereas O2- production by
      neutrophils derived from patients receiving G-CSF could be further augmented by
      TNF but not by GM-CSF. Interestingly, neutrophils from patients treated with GM
      CSF but not those with G-CSF therapy retained a higher response to in vitro
      stimulation with GM-CSF or TNF after the end of CSF administration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584672
TI  - Spontaneous release of interleukin-6 by primary cultures of lymphoid and tumor
      cell populations purified from human ovarian carcinoma.
AB  - Interleukin-6 (IL-6) is a cytokine that has been implicated as a growth factor in
      human ovarian carcinoma, yet the in vivo source of IL-6 in patients remains
      undefined. We measured IL-6 by ELISA in cell-free ascites (CFA) of 19 patients
      with ovarian carcinoma. IL-6 was detectable in all samples (mean level 3.3
      ng/ml). To identify the cellular source of IL-6, we measured this cytokine by
      ELISA in 24-48 h supernatants of cultured lymphocyte-, macrophage-, and tumor
      cell-enriched populations purified from three solid ovarian carcinomas by
      centrifugal elutriation. All cell populations spontaneously released IL-6;
      however, tumor cells and tumor-associated macrophage released levels of IL-6 that
      greatly exceeded those released by tumor-associated lymphocytes. Kinetic studies
      revealed that IL-6 was detectable at 6 h and that levels increased in all
      cultures examined over a 48 h time course. These data suggest that both tumor and
      infiltrating host cells may be the source of the high levels of IL-6 found in
      carcinomatous ascites. Furthermore, although all three cell types examined may
      contribute to IL-6 production in patients with ovarian carcinoma, tumor cells are
      perhaps the most clinically significant source.

PMID- 7584673
TI  - Cytokine expression in large cell lymphoma associated with acquired
      immunodeficiency syndrome.
AB  - Cytokine expression was examined by reverse transcriptase-polymerase chain
      reaction (RT-PCR) in a retrospective sampling of 16 AIDS-associated large cell
      lymphomas (LCL). IL-6 receptor (IL-6R) and IL-10 expression was detected in a
      majority of the tumor specimens tested, IL-6 expression was detected in 5 of 16
      lymphomas that also expressed IL-6R, suggestive of an autocrine mechanism of
      disease. A subset of tumor samples described as mixed immunophenotype contained
      large numbers of infiltrating T lymphocytes and macrophages. Immunoperoxidase
      staining of a representative tumor of mixed immunophenotype demonstrated the
      presence of HIV-infected macrophages that also stained with anti-IL-6. This
      finding suggests that IL-6 produced by nonlymphoid cells may act as a paracrine
      growth factor for tumor cells that express IL-6R. Although earlier studies of
      AIDs burkitt's lymphoma cell lines suggested that IL-10 expression required EBV
      infection, 7 of 12 AIDS LCLs that expressed IL-10 did so in the absence of EBV by
      EBER in situ hybridization. Because AIDS LCLs frequently express cell surface
      CD5, we speculate that IL-10 may act as an autocrine or paracrine growth factor
      for this class of lymphoma. These studies suggest that IL-6 and IL-10 are
      involved in the pathogenesis of AIDS-associated large cell and mixed
      immunophenotype lymphoma.

PMID- 7584674
TI  - Immunologic effects of low-dose polyethylene glycol-conjugated recombinant human
      interleukin-2 in common variable immunodeficiency.
AB  - Children or adults with the primary immunodeficiency disease, common variable
      immunodeficiency (CVI), have abnormally low levels of at least two of the three
      serum Ig isotypes. Although there appear to be intrinsic B cell defects, many
      have poor T cell proliferation and deficient secretion of IL-2, IL-4, IL-5
      interferon-gamma, and B cell differentiation factor. Because the addition of
      various T cell factors can enhance Ig secretion in vitro in CVI, we have
      hypothesized that the B cells in this disease may be defective because they lack
      appropriate investigating the in vivo effects of recombinant IL-2 using a new
      biologic, polyethylene glycol-conjugated recombinant IL-2 (PEG-IL-2). In these
      studies, CVI patients were treated with weekly subcutaneous injections of PEG-IL
      2. After 12 weeks, each patient had enhanced T cell proliferation, normal IL-2
      production, boosted BCDF secretion, and B cells responsive to differentiation
      signals. During PEG-IL-2 treatment, four of five patients produced detectable
      serum antibody to keyhole limpet hemocyanin. These data suggest that CVI, which
      has the phenotype of B cell deficiency, may be caused by a lack of appropriate T
      cell signals for B cell maturation.

PMID- 7584676
TI  - Lymphocyte markers and disease activity in asthma.

PMID- 7584675
TI  - Desperately seeking a solution--total serum immunoglobin E and airways
      obstruction.

PMID- 7584677
TI  - Sulfite sensitivity.

PMID- 7584678
TI  - Total serum IgE and FEV1 by respiratory symptoms and obstructive lung disease in
      adults of a Norwegian community.
AB  - BACKGROUND: The importance of total serum IgE level on lung function impairment
      has not been established in a general population. OBJECTIVE: The aim of this
      cross-sectional community study was to examine the relationship between total
      serum IgE and level of lung function in adults, and whether this relationship
      differed by sex, age, smoking habits or by respiratory symptoms and disease
      status. METHODS: A stratified random sample of 18-73 year old adults from the
      general population were invited to spirometry and serum analyses of total and
      specific IgE. Of 1512 subjects invited, 82% met and performed complete
      examinations. RESULTS: Increasing level of total serum IgE was related to reduced
      lung function (P < 0.01) given as sex, age, and height standardized residuals of
      one second forced expiratory volume (SFEV1). Subjects with total serum IgE in the
      highest vs the lowest tertile had a mean SFEV1 of -0.28, corresponding to age and
      height adjusted FEV1 differences of 120 and 150 mL in women and men,
      respectively. The relationship between IgE and lung function impairment did not
      differ significantly by sex, age or smoking habits. In subjects with obstructive
      lung disease increasing level of total serum IgE was more negatively associated
      with lung function level than in subjects with respiratory symptoms alone. No
      relationship was observed in asymptomatic subjects. This was confirmed in a
      multiple linear regression analysis adjusting for sex, age, smoking habits and
      lifetime smoking consumption showing that SFEV1 was predicted by an interaction
      between total serum IgE level and symptom and disease status (P < 0.01). This
      interaction remained after excluding subjects (n = 105) having specific IgE
      antibodies. CONCLUSION: Increasing total serum IgE level was associated with
      progressively lower lung function in a general adult population after taking
      other predictors of impaired spirometric lung function into account, though
      dependent on the subjects' respiratory symptom and disease status. Variation in
      prevalences of respiratory symptoms and obstructive lung disease in previous
      examined populations may thus explain conflicting observations of the association
      between total IgE and airflow impairment.

PMID- 7584680
TI  - Pickled onion-induced asthma: a model of sulfite-sensitive asthma?
AB  - BACKGROUND: Asthma elicited by sulfite ingestion has been mainly described in
      steroid-dependent and in non-atopic asthmatics. We have studied a group of 18
      young extrinsic asthmatics who presented with asthma attacks immediately after
      eating pickled onions. OBJECTIVE: The aim of this study is to ascertain if these
      asthma attacks are elicited by sulfites contained in pickled onions and the
      influence of the dose and pH of onions. METHODS: The bronchial hyperreactivity of
      the patients was assessed by a methacholine challenge test. Oral challenge tests
      were performed with sodium metabisulfite (MSB) diluted in lemon juice at pH 4.2
      and at pH 3.3 (only in patients who did not react with pH 4.2). Two types of
      pickled onions, Spanish and Dutch pickled onions, were used for oral challenge in
      seven of the patients. The Monier-Williams method was used to measure the SO2
      concentration in pickled onions. RESULTS: The oral provocation test with MBS, pH
      4.2, elicited a positive response in six patients (33.3%) and the test at pH 3.3
      was positive in three out of 12. No significant difference in PD20 values was
      found between these groups. Three of the seven patients challenged with Spanish
      pickled onions had a positive reaction but had no reaction with Dutch pickled
      onions. The SO2 concentration in Spanish pickled onions varied between 765 and
      1182 ppm while in Dutch pickled onions were 200 ppm; this exceeded the permitted
      level (100 ppm). SO2 release in Spanish pickled onion samples was nearly 2.5
      times higher when the pH of the sample decreased from 4.2 to 3.3. CONCLUSION:
      High levels of SO2 in Spanish pickled onions, and their low pH (3.3) would be the
      responsible factors of the asthmatic outbreaks after ingestion of Spanish pickled
      onions by these patients.

PMID- 7584681
TI  - Tryptase and histamine release due to a sting challenge in bee venom allergic
      patients treated successfully or unsuccessfully with hyposensitization.
AB  - BACKGROUND: Hyposensitization with been venom leads to full protection in most,
      but not all patients with IgE-mediated systemic reactions to bee stings.
      OBJECTIVE: To determine the relationship of clinical reactivity to the release of
      mediators and to changes of antibody concentrations in the peripheral circulation
      at a bee sting challenge test. METHODS: Blood was sampled before (1 min) and at
      15, 60 and 180 min after a sting challenge from 19 patients on hyposensitization.
      Of these six still reacted and 13 were protected. Histamine, mast cell tryptase,
      bee venom-specific IgE and IgG in the serum, and histamine release from
      peripheral blood leucocytes (PBL) upon exposure to bee venom were determined.
      RESULTS: Tryptase above the detection level was found only at 15 (60) min in 4/6
      (1/6) patients who reacted. After the sting challenge there was a significant
      increase of the histamine levels in patients who reacted at 15 min (P < 0.05) and
      in patients who did react at 60 and 180 min (P < 0.01). The total histamine
      content of PBL was significantly decreased after 15 and 60 min in patients who
      reacted (P < 0.01) and in those that did not (P < 0.05). Bee venom-induced
      histamine release was significantly reduced in patients reacting and those that
      did not at 15 min (P < 0.05), and was significantly decreased in reactors also at
      60 and 180 min (P < 0.05/0.01). Specific IgG antibodies showed a minor decrease
      (P < 0.05) after the sting challenge in both groups, whereas specific IgE did not
      change significantly. CONCLUSION: These results indicate that bee venom
      anaphylaxis is associated with the release of mediators from both mast cells as
      well as basophils. Successful hyposensitization does not induce a state of
      immunological non-reactivity, but rather alters the magnitude and the pattern of
      mediator release.

PMID- 7584679
TI  - Effect of an asthmatic attack on CD23 and CD21 expression on lymphocytes from
      allergic children during the allergen season.
AB  - BACKGROUND: The overproduction of IgE antibodies by atopic individuals in
      response to inhaled aeroallergen, forms the basis of an allergic disease.
      Furthermore, the exposure to allergen might trigger the symptom exacerbation.
      OBJECTIVE: In children with bronchial asthma, the possible effects of seasonal,
      natural exposure to allergen on the expression of CD21 and CD23 antigens on B
      lymphocytes, and on the expression of HLA-DR, CD45RA and CD45RO on CD4+ T cells
      investigated. METHODS: Heparinized blood samples were obtained from 15 children
      with bronchial asthma allergic to Dermatophagoides pteronyssinus (Der p) at the
      time of an acute asthmatic attack and 2-4 weeks after the attack when the peak
      expiratory flow (PEF) was stabilized. The samples were analysed on a flow
      cytometer after the three-colour immunofluorescence staining had been performed.
      RESULTS: The increased proportion of B cells expressing CD23 antigen was found at
      the time of attack rather than after stabilization. Serum levels of total and Der
      p-specific IgE increased 2-4 weeks after the asthmatic attack. This increase was
      accompanied by a further increase in the expression of CD23 antigen on CD21- B
      lymphocytes. In 10 out of 15 tested children, we found CD23 expressed on CD4+HLA
      DR+ T cells during the asthmatic attack. No significant difference was found in
      the expression of CD45RA and CD45RO. CONCLUSION: Since we have previously
      demonstrated the increased percentage of CD23 on CD21- B cells in allergic
      children as compared with controls, we speculate that natural exposure to the
      allergen which caused the increase in total and specific IgE levels might be
      related to the increased expression of CD23 on CD21- B cells.

PMID- 7584683
TI  - IL-5, IL-8 and GM-CSF immunostaining of sputum cells in bronchial asthma and
      chronic bronchitis.
AB  - BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) and
      interleukin (IL)-5 or IL-8 have been suggested to play an important role in the
      pathogenesis of eosinophilic airway inflammation in bronchial asthma or
      neutrophilic airway inflammation in chronic bronchitis, respectively, However, GM
      CSF and IL-8 have biological activities to either eosinophils or neutrophils.
      OBJECTIVE: To investigate the contribution of these cytokines to airway
      inflammation, we compared the cellular differential and immunolocalization of GM
      CSF, IL-5 and IL-8 in sputum cells from patients with bronchial asthma and
      chronic bronchitis. METHODS: Cytospins of sputum cells from 12 patients with
      bronchial asthma and 12 with chronic bronchitis were subjected to cellular
      differential counting and immuno-cytochemistry with anti-human GM-CSF, IL-5 and
      IL-8 antibody. RESULTS: The predominant cells in bronchial asthma were
      eosinophils and lymphocytes, while those in chronic bronchitis were neutrophils.
      All cytokines examined were detected in either bronchial asthma or chronic
      bronchitis, although the percentage of GM-CSF and Il-5 positive cells in
      bronchial asthma (53.4 +/- 6.0 [mean +/- SEM]% and 9.7 +/- 2.8%, respectively)
      was significantly higher than that in chronic bronchitis (11.4 +/- 2.5%; P <
      0.001 and 1.7 +/- 0.3%; P < 0.007, respectively). In contrast, the percentage of
      IL-8 positive cells in chronic bronchitis (23.8 +/- 7.0%) was significantly
      higher than that in bronchial asthma (7.& +/- 1.9%; P < 0.04). The cells positive
      for IL-5 were lymphocytes in bronchial asthma and chronic bronchitis. The cells
      positive for GM-CSF in bronchial asthma were predominantly eosinophils, while
      those in chronic bronchitis were monocytes/macrophages and neutrophils. In
      contrast, neutrophils are mainly positive for IL-8 in chronic bronchitis, while
      monocytes/macrophages and bronchial epithelial cells are positive for IL-8 in
      bronchial asthma. CONCLUSION: The immunochemical comparison of GM-CSF and IL-8
      localization in sputum cells between bronchial asthma/chronic bronchitis suggests
      the differential regulation and roles of these cytokines in eosinophilic vs
      neutrophilic airway inflammation, resulting in the development of different types
      of airway inflammation.

PMID- 7584682
TI  - The differential release of eosinophil granule proteins. Studies on patients with
      acute bacterial and viral infections.
AB  - BACKGROUND: Earlier in vitro studies have suggested that the eosinophil may
      release its granule proteins selectively depending on the stimulus to which the
      cell is exposed. OBJECTIVE: The object of the present study was to study the
      question of selective release in vivo by means of serum measurements of the two
      eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil
      peroxidase (EPO) in acute infections. METHODS: Fourty-six subjects with acute
      infections were studied before treatment, 20 with bacterial infections and 26
      with viral infections. Serum ECP, EPO and MPO were measured by specific RIA.
      RESULTS: In acute bacterial infections ECP, but not EPO, was significantly raised
      in serum (P < 0.0001) compared with non-infected healthy subjects. In acute
      bacterial infections ECP was significantly correlated to the levels of the
      neutrophil marker myeloperoxidase (MPO) (rs = 0.96, P < 0.0001) but not to EPO.
      In acute viral infections neither ECP nor EPO were on average raised. However,
      almost 20% the patients had elevated levels of bot proteins. In the viral
      infections the serum-levels of ECP and EPO were correlated (rs = 0.63, P <
      0.001), but no correlation was found with MPO. CONCLUSION: It is concluded that
      eosinophils are activated during acute bacterial infections and that this
      activation results in the preferential mobilisation of ECP. The simultaneous
      assay of the two eosinophil proteins, ECP and EPO, may give new insight into the
      role of the eosinophil in disease.

PMID- 7584684
TI  - Leukotriene B4 production by blood neutrophils in allergic rhinitis--effects of
      cetirizine.
AB  - BACKGROUND: Mucosal inflammatory processes in late phase of allergic diseases
      involve cytokine production, cell adhesion molecule overexpression and release of
      inflammatory mediators with chemotactic activity, such as leukotriene B4 (LTB4).
      We had previously observed increased production of LTB4 by neutrophils in
      patients with allergic rhinitis and discussed the role of granulocyte macrophage
      colony stimulating factor (GM-CSF) priming. Some antihistaminic compounds were
      shown to diminish the production of leukotrienes by neutrophils. OBJECTIVES: In a
      first step, we evaluated in ex vivo and in vitro studies, the effects of
      cetirizine on LTB4 production by blood neutrophils from allergic and healthy
      subjects. In a second step, we studied the in vitro effect of cetirizine on LTB4
      production by neutrophils from healthy subjects during GM-CSF priming of these
      cells. METHODS: Neutrophils from both populations were purified from venous blood
      and LTB4 production was measured using high performance liquid cromatography
      (HPLC) method. RESULTS: In ex vivo studies, cetirizine treatment induced a
      decreased LTB4 production by neutrophils in allergic rhinitis. This effect of
      decreased LTB4 production was reproduced in vitro with 10(-8)-10(-6)M cetirizine.
      Nevertheless, this anti-H1 compound had no effect on neutrophil priming with GM
      CSF. CONCLUSION: As LTB4 is an important chemotactic factor, Cetirizine could act
      on inflammatory cell recruitment by inhibiting LTB4 production by neutrophils.

PMID- 7584686
TI  - Soluble ICAM-1 as a regulator of nasal allergic reaction under natural allergen
      provocation.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) plays a key role in the
      early stage of the signal cascade leading to cellular extravasation and
      development of an inflammatory response. Recently, it has been reported that the
      soluble form of this adhesion molecule is present in human sera, possibly
      mediating biological actions. OBJECTIVE: The purpose of this study was to
      investigate levels of soluble ICAM-1 (sICAM-1) and its receptors in patients with
      allergic rhinitis, and to discuss sICAM-1's biological function. METHODS: The
      levels of sICAM-1 in sera and nasal epithelial lining fluids (ELF), the
      percentage of CD11a-positive lymphocytes in the peripheral blood, and scores of
      subjective symptoms from 14 patients with pollinosis (allergic group) were
      measured from pre- to post-season, results were compared with those from 10 non
      allergic subjects (control group). RESULTS: The levels of sICAM-1 in sera and ELF
      were upregulated, and CD11a-positive lymphocytes were downregulated during the in
      season in the allergic group. In addition, levels of sICAM-1 sera from the
      allergic group remained high during the post-season, when levels of other
      parameters (symptoms, blood eosinophil counts, sICAM-1 in ELF and CD11a-positive
      lymphocytes) had roughly returned to the initial pre-season levels. CONCLUSIONS:
      We demonstrate systemic and local upregulation of sICAM-1 and systemic
      downregulation of LFA-1 positive lymphocytes in patients with seasonal allergic
      rhinitis under natural allergen provocation, suggesting that sICAM-1 plays a role
      in regulating seasonal allergic inflammation.

PMID- 7584687
TI  - An increased frequency of IgE-producing B cell precursors contributes to the
      elevated levels of plasma IgE in atopic subjects.
AB  - BACKGROUND: The production of specific IgE, which underlies the allergic
      response, may be a normal correlate of the immune response to a certain class of
      antigen (allergens), or could represent a unique response driven by regulatory
      signals that are absent in non-allergic individuals. If atopic subjects do
      possess a regulatory environment favoring IgE production, they may display not
      only allergen-specific IgE, but also higher levels of total IgE and higher
      frequencies of IgE-producing B lymphocytes. OBJECTIVE: To address the
      contribution of antibody-producing cell number to the circulating IgE titre in
      atopic vs non-atopic subjects. METHODS: Frequency determination by limiting
      dilution of EBV transformants and Poisson distribution analysis. Titres of total
      and allergen-specific IgM, IgG, and IgE by specific ELISA. RESULTS: In contrast
      to findings reported by others, the atopic subjects had a significantly higher
      frequency of IgE-producing B cells than non-atopics (0.79% of total Ig-producing
      cells, as compared with 0.17% for the control group; P < 0.01), suggesting that
      one factor contributing to the high plasma IgE titres in atopic subjects is the
      high frequency of B lymphocytes with the potential to produce IgE. Although only
      the atopic subjects produced allergen-specific IgE, the frequency of specific IgE
      producing B cells was undetectable in both groups. CONCLUSION: Atopic subjects
      have higher frequencies of IgE-producing B cell precursors than non-atopics. A
      correlation exists between IgE-producing B cell frequency and levels of
      circulating IgE.

PMID- 7584685
TI  - A placebo-controlled study of fluticasone propionate aqueous nasal spray and
      beclomethasone dipropionate in perennial rhinitis: efficacy in allergic and non
      allergic perennial rhinitis.
AB  - BACKGROUND: Fluticasone propionate is a new potent, topically active
      corticosteroid with negligable oral bioavailability. Data on its comparative
      efficacy in perennial allergic and non-allergic rhinitis are limited. OBJECTIVE:
      To compare the efficacy and safety of fluticasone propionate aqueous nasal spray
      (FPANS) 200 micrograms once or twice daily with beclomethasone dipropionate
      aqueous nasal spray (BPD) 200 micrograms twice daily and placebo in patients with
      allergic and non-allergic perennial rhinitis. METHODS: The 12-week study had a
      multicentre, double-blind, randomized, parallel group design. Efficacy was
      assessed from symptom scores recorded on daily diary cards. RESULTS: FPANS 200
      micrograms once or twice daily was significantly better than placebo but not
      better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose
      was equally effective in the treatment of allergic and non-allergic perennial
      rhinitis. There were few adverse events and no treatment-related abnormalities in
      laboratory measurements in either FPANS-treated group. Comparison between
      treatment groups indicated that FPANS was as well tolerated as placebo and BDP at
      the doses studied. CONCLUSIONS: In the majority of patients FPANS 200 micrograms
      once daily in as effective as BDP 200 micrograms twice daily in the relief of
      perennial allergic rhinitis.

PMID- 7584688
TI  - Increased serum IgE in alcohol abusers.
AB  - BACKGROUND: It has been reported that total serum IgE is increased in patients
      with alcoholic cirrhosis, but it is not clear if this fact is related to
      alcoholic liver disease or to alcohol intake. OBJECTIVE: To measure serum IgE in
      a group of chronic alcoholics with different stages of liver injury in order to
      elucidate if IgE increase in related to alcoholic liver damage. PATIENTS AND
      METHODS: Total serum IgE was determined by enzyme immunoassay in 186 chronic
      alcoholic patients (137 male/49 female) and 101 healthy controls. Patients and
      controls with known reasons for IgE elevation were excluded. Among alcoholic
      patients, 24 had fatty liver, 28 hepatic fibrosis, 29 alcoholic hepatitis, and 67
      liver cirrhosis (38 patients were not evaluable concerning liver injury).
      RESULTS: Total serum IgE was found to be increased in alcoholics (median 154.5
      IU/mL, range 1-7329 IU/mL) with respect to healthy controls (median 20 IU/mL,
      range < 1-1417 IU/mL) (P < 0.001). IgE increase was moderate (180-1000 IU/mL) in
      60 alcoholics (32.3%) and marked ( > 1000 IU/mL) in 27 (14.5%). Male alcoholics
      had higher IgE levels than females (median 191 IU/mL and range 1-7329 IU/mL vs
      105 IU/mL and range 2-2189 IU/mL) ( P = 0.009). On logistic regression analysis,
      alcoholism, male sex and younger age (but not smoking) were independently
      associated with higher IgE levels. No clear relationship was noted between serum
      IgE and severity of alcoholic liver disease. Thus, no correlation was observed
      between IgE and parameters of liver function (serum bilirubin, albumin or
      prothrombin index). Likewise, IgE concentrations were not significantly different
      in patients with liver cirrhosis with respect to patients with less severe liver
      disease. Serum IgE was increased ( > 180 IU/mL) in 47.8% of cirrhotics and in 44%
      of patients without liver cirrhosis. In contrast, other immunoglobulins (IgG, IgA
      and IgM) were significantly correlated with liver dysfunction. CONCLUSION:
      Chronic alcoholism should be considered as a cause of increased total serum IgE,
      regardless of the severity of the underlying liver disease.

PMID- 7584689
TI  - The decay of house dust mite allergens, Der p I and Der p II, under natural
      conditions.
AB  - BACKGROUND: Fluctuations in the level of mite allergens in domestic house dust
      are the result of changes in the balance between synthesis, removal and decay.
      Purely physical forces as well as enzymatic degradation, mediated by house dust
      inhabiting microbes, may contribute to the decay of allergens in domestic dust.
      Knowledge about the speed of decay is essential for an understanding of the
      dynamics of allergen levels. OBJECTIVE: The present study is a quantitative
      assessment of the speed of decay at nine combinations of temperature (15 degrees
      C, 20 degrees C and 25 degrees C) and relative humidity (33%, 55% and 75%).
      METHODS: Samples of mite infested material of an old rug were stored at these
      temperature/relative humidity-combinations for 6, 12 or 18 months, after the
      mites were killed by either a freezing treatment or an acaricide (lindane). The
      microbes living in the rug presumably survive these treatments. Concentrations of
      Der p I and Der p II + Der f II, in extracts of the rug material, were measured
      by radio immunoassay. RESULTS: No significant changes in the levels of der p I
      and Der p II + Der f II, could be detected even after 1 1/2 year at a high
      temperature and humidity. CONCLUSION: These findings indicate that mite allergens
      can be extremely stable under normal domestic circumstances.

PMID- 7584690
TI  - Asthma mechanisms, determinants of severity and treatment: the role of nedocromil
      sodium. Report of a workshop held in Whistler, British Columbia, Canada, 18-19
      May 1995.

PMID- 7584691
TI  - The timing of sexual maturation in a group of US white youths.
AB  - The purpose of this study was to present US reference data for chronological ages
      at which stages of sexual maturation were observed in white youths. Recent serial
      data from 78 males and 67 females were analyzed to obtain descriptive statistics
      for the ages at onset of these stages and the mean ages at which the stages are
      observed. These reference data should assist the identification of white US
      youths who are maturing at rapid or slow rates and the interpretation of growth
      data.

PMID- 7584692
TI  - Characterization of zona glomerulosa function in patients with classic and non
      classic forms of congenital adrenal hyperplasia due to 11 beta-hydroxylase
      deficiency.
AB  - The function of the adrenal zona glomerulosa was studied in 18 patients with 11
      hydroxylase deficiency confirmed by elevated plasma levels of 11-deoxycortisol.
      Patients were divided into two groups. Group I (4 males, 7 females; aged 1.2-2.8
      yrs) had symptoms at birth or shortly after (classic form), and Group II (4
      males, 3 females; aged 7.3-20.1 yrs) had their first clinical manifestation
      during childhood (non-classic form). To study zona glomerulosa function, patients
      were given dexamethasone p.o. 2 mg/m2/day x6 days, thus suppressing the zona
      fasciculata. Six hours after the last dose of dexamethasone, the zona glomerulosa
      was stimulated by i.v. administration of furosemide 1.0 mg/kg as a single dose.
      Blood was drawn 2 h later. In the untreated state, all patients had striking
      elevation of ACTH (Group I: 1,070 +/- 380 pg/ml; Group II: 764 +/- 180 pg/ml), 11
      deoxycortisol (Group I: 63,000 +/- 22,000 ng/dl; Group II: 17,200 +/- 5,200
      ng/dl) and deoxycorticosterone (Group I: 1,100 +/- 67 ng/dl; Group II: 499 +/- 27
      ng%) while plasma renin activity (< 0.5 ng/ml/h in both groups) and aldosterone
      (Group I: 3.0 +/- 1.8 ng/dl; Group II: 2.3 +/- 1.8 ng/dl) were markedly
      suppressed. After the administration of furosemide 4 patients in Group I were
      unable to increase aldosterone (2.8 +/- 0.9 ng/dl) secretion in spite of marked
      elevation of plasma renin activity (28 +/- 7 ng/ml/h), suggesting an impairment
      of 11-hydroxylase in the zona glomerulosa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584693
TI  - Single intravenous bolus of dexamethasone for the differential diagnosis of
      Cushing's syndrome.
AB  - We developed a 24 hour intravenous dexamethasone suppression test for the
      differential diagnosis of Cushing's syndrome. Basal ACTH and cortisol levels were
      measured at 8 and 9 AM; a bolus of 8 mg dexamethasone phosphate (in children 5
      mg/m2) was administered intravenously, and cortisol levels were measured hourly
      until 3 PM, then every 2 hours until midnight, and the next morning at 8 and 9
      AM. We studied 13 patients with an ACTH-secreting pituitary adenoma, four with an
      autonomous adrenal adenoma, a 10 year-old girl with primary adrenocortical
      nodular dysplasia, one male with an ACTH-secreting medullary carcinoma of the
      thyroid, and one male with an ACTH-secreting non-small cell carcinoma of the
      lung, and compared their results to those obtained in 8 lean and 12 obese normal
      individuals (controls). The clinical diagnosis was first ascertained by the
      response to the oral administration of dexamethasone in low and high doses
      (standard Liddle test), then by the intravenous dexamethasone suppression test,
      and finally confirmed surgically. Although both controls and patients with an
      ACTH-secreting pituitary adenoma significantly suppressed their cortisol levels
      within hours after the injection (50% reduction of basal value at 2 hours, and
      75% at 4 hours, p < 0.0001), levels remained suppressed the next morning only in
      the controls, while in the patients they returned to basal values. No suppression
      was observed in any of the patients with an adrenal adenoma and the child with
      primary adrenocortical nodular dysplasia (whose ACTH levels were low), or in the
      patients with ectopic ACTH secretion tumors (whose ACTH levels were
      high).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584694
TI  - Exposure to superantigens as an immunogenetic explanation of type I diabetes mini
      epidemics.
AB  - Insulin-dependent diabetes mellitus (IDDM) is considered to be an autoimmune
      disease. Autoimmune diseases result from the breakdown of self-tolerance elicited
      by environmental factors on a susceptible genetic background. This reduced
      tolerance allows immunocompetent cells to attack normal structures present on an
      individual's tissues. The study of the T cells present in the islets of patients
      who died at the onset of the disease allowed the recognition of "superantigens"
      as etiopathogenetic factors in the development of IDDM. Since superantigens are
      the product of bacteria or viruses able to quickly stimulate a large number of
      the peripheral T cells sharing the same T cell receptor V beta segments once
      presented by certain HLA class II molecules, a number of observations in
      genetics, immunology, virology and epidemiology can now find a unifying
      explanation.

PMID- 7584695
TI  - Comparison between spinal and radial bone mineral density in children measured by
      X-ray absorptiometry.
AB  - Several studies have analyzed the correlation between axial bone mineral density
      (BMD) measured by dual X-ray absorptiometry (DXA) and growth parameters. However,
      little is known about the growth-related changes in appendicular BMD measured by
      this technique. We used DXA to measure BMD in the lumbar spine (L1-L4) and distal
      radius in 121 normal growing children (69 boys, 52 girls), aged 3 to 18 yr. Both
      lumbar and radius BMD showed a steady increase with age and a steeper increment
      during puberty. There was a good correlation between spinal and radial BMD (r =
      0.83; p < 0.001) and both were highly correlated with growth parameters; their
      respective correlation coefficients did not differ significantly for
      chronological age (r = 0.70 vs 0.80), weight (r = 0.77 vs 0.76), height (r = 0.73
      vs 0.79), body surface (r = 0.78 vs 0.80), body mass index (r = 0.54 vs 0.49) and
      bone age (r = 0.77 vs 0.79). By multiple regression analysis the best predictors
      for spinal BMD were bone age, pubertal stage and weight, while for radial BMD the
      best predictors were chronological age and weight. We have shown that the
      measurement of BMD by DXA at distal radius, an easily accessible bone, has a
      correlation with growth parameters as good as lumbar spine BMD measurements in
      children.

PMID- 7584698
TI  - Pachydermoperiostosis in a 13 year-old boy presenting as an acromegaly-like
      syndrome.
AB  - A thirteen year-old boy with progressive enlargement of the joints and distal
      extremities, clubbing, coarse facial features and hyperhidrosis was investigated.
      His endocrine profile was normal. Radiological studies demonstrated bilateral
      symmetrical periosteal new bone formation with acroosteolysis. After extensive
      investigation to exclude systemic and endocrine causes, a diagnosis of
      pachydermoperiostosis was made. Awareness of this condition helps to
      differentiate this syndrome from pulmonary osteoarthropathy and acromegaly.

PMID- 7584697
TI  - Thyrotropin secreting pituitary adenoma associated with hypopituitarism and
      diabetes insipidus in an adolescent boy.
AB  - A 13 year-old boy was referred to our hospital because of several months of
      school performance deterioration, behavioral changes and secondary enuresis.
      Hyperthyroidism, diabetes insipidus and hypopituitarism due to thyrotropin
      secreting pituitary macroadenoma were found. Six weeks of therapy with octreotide
      failed to reduce the serum TSH levels and the tumor size. Transsphenoidal
      pituitary surgery had a transient effect on serum TSH levels as the patient
      redeveloped hyperthyroidism with elevated serum TSH levels. Several months had
      elapsed from the time the patient first presented with the symptoms to the time
      the diagnosis was made. Thyrotropin secreting pituitary adenoma is a rare cause
      of hyperthyroidism. Recognizing the signs of the disease might lead to early
      diagnosis and might improve the prognosis.

PMID- 7584696
TI  - Short term effect of intranasal administration of hexarelin--a synthetic growth
      hormone-releasing peptide. Preliminary communication.
AB  - Twice or three times daily intranasal administration of the hexapeptide hexarelin
      for 7 days to children with short stature and normal growth hormone (GH)
      secretion evoked a significant rise in serum levels of insulin-like growth factor
      1 (IGF-1) and alkaline phosphatase. There was also a significant, within normal
      limits, rise of thyroid stimulating hormone (TSH) without evidence of thyroxine
      suppression.

PMID- 7584699
TI  - Hypopituitarism and chorioretinopathy in two siblings.
AB  - Two male siblings with chorioretinopathy and pituitary dysfunction (CPD) were
      found to have empty sellas on CT scan. Extensive ophthalmological and
      endocrinological investigation revealed the absence of gonadotrophins in both
      brothers and growth hormone deficiency in one. ACTH, TSH, and posterior pituitary
      function were normal. Karyotyping in one brother revealed a 46XY complement.
      Ophthalmological evaluation of three other siblings and both parents revealed
      normal vision and no evidence of retinopathy. The brothers represent two
      additional examples of CPD syndrome, suggesting a genetic etiology for this
      syndrome complex. The empty sellas present add another facet to the central
      nervous system disorders found in CPD syndrome.

PMID- 7584700
TI  - Pseudohypoaldosteronism: report of a case presenting as failure to thrive.
AB  - We report a 2 month-old infant referred for failure to thrive. At birth, weight
      was 3820 g and length 52 cm. After physiologic weight loss, the patient showed no
      further weight gain for the next two months. On admittance (age 2 mo), weight was
      3340 g and length 53 cm; the infant had severe dystrophy, generalized hypotonia
      and dehydration; blood chemistry showed hyponatremia, hyperkalemia and
      hypochloremia. A salt losing syndrome of adrenal origin was hypothesized.
      However, rehydration and hydrocortisone administration failed to correct
      hyponatremia and hyperkalemia. Endocrine assessment showed high levels of
      aldosterone and plasma renin activity, suggesting pseudohypoaldosteronism. Oral
      sodium chloride supplementation normalized electrolyte balance and the patient
      showed progressive weight gain and catch-up growth, confirming the diagnosis.

PMID- 7584701
TI  - Male pseudohermaphroditism with 5-alpha-reductase deficiency: report of two new
      familial cases. The importance of early diagnosis.
AB  - We report two new familial cases of male pseudohermaphroditism due to 5-alpha
      reductase deficiency, from the south of Spain. They were born with ambiguous
      genitalia and were reared as females. At the time of puberty, both brothers
      virilized partially and underwent a change of gender role from female to male
      with a stormy psychic readjustment period. We stress the value of the prolonged
      chorionic gonadotropin test for an early diagnosis.

PMID- 7584702
TI  - Turner's syndrome and hypogonadotrophic hypogonadism: thalassemia major and
      hemochromatosis.
AB  - We report here the first case of an association between thalassemia major,
      hemochromatosis, hypogonadotrophic hypogonadism and Turner's syndrome. The
      patient is an Albanese girl born in 1980; thalassemia major was diagnosed at 1
      year and she was started on a transfusion program; in 1987 iron chelation therapy
      was started. Six years ago, at 7 years of age, her short stature was observed and
      she was referred to the endocrinology clinic for evaluation; the basal and
      stimulation tests done at that time failed to reveal growth hormone deficiency,
      hypothyroidism or any other disease. Nevertheless, at 12 years old, she was still
      prepubertal and there was a bone age delay of 1.5 years; a gonadotropin-releasing
      hormone (GnRH) stimulation test showed no response of either FSH (basal: 0.2
      mU/ml; peak: 0.8 mU/ml) or LH (basal: < 0.1 mU/ml; peak: 0.6 mU/ml), suggesting
      hypogonadotrophic hypogonadism. Small dysmorphies called our attention to the
      possibility of Turner's syndrome which was confirmed by the karyotype (45 XO/46
      XX). In this patient, thalassemia major and its lifelong consequences, namely the
      hemochromatosis-related hypogonadotrophic hypogonadism, masked the usual hormonal
      findings of Turner's syndrome.

PMID- 7584703
TI  - Determination of body composition in children and adolescents: validation of
      bioelectrical impedance with isotope dilution technique.
AB  - The determination of body composition as part of the clinical and auxologic
      follow up of childhood growth disorders necessitates the use of a quick,
      portable, reliable and simple non-invasive method. The present study was
      undertaken to validate bioelectrical conductance, height2/resistance (Ht2/R),
      against isotopically determined total body water (TBW) using heavy water tracer
      H2[18O]. The subjects (n = 56) consisted of normal children, children with
      various endocrine disorders, and young adults between the ages of 8-26 years.
      Isotopically determined TBW and fat free mass (FFM) were highly correlated with
      Ht2/R (r = 0.94, p = < 0.001, and r = 0.94, p = < 0.001, respectively). In a
      multiple regression analysis, 96% of the variability in FFM in normal subjects
      could be predicted by the following equation: FFM = 0.524 Ht2/R + 0.415 Wt-0.32,
      while in the group of patients by FFM = 0.659 Ht2/R + 0.254 Wt + 2.851. These
      data suggest that bioelectrical impedance measurements give valid and reliable
      estimates of FFM in children and adolescents. This easy technique could be
      incorporated in the auxologic follow up of children on hormone therapy.

PMID- 7584704
TI  - Comparison of transdermal and oral estrogen therapy in girls with Turner's
      syndrome.
AB  - Eight girls with Turner's syndrome were given low dose oral ethinyl estradiol or
      transdermal 17 beta-estradiol in order to compare the effect of the route of
      administration on selected markers of hepatic metabolism, and various hormonal
      concentrations. Oral estrogen was given at a dose of 100 ng/kg/day and
      transdermal estrogen via adhesive skin patch at 0.0125 mg/kg/day. The subjects
      received one form of estradiol for one month, and after a one month washout
      period, received the other form. Both oral and transdermal estradiol caused a
      significant decrease in FSH while only transdermal resulted in a significant
      decrease in LH. Oral estradiol, though not transdermal estradiol, increased serum
      high density lipoprotein, thyroxine binding protein and growth hormone binding
      protein. Urinary growth hormone excretion increased after both forms of therapy,
      while insulin-like growth factor-I and insulin-like growth factor binding protein
      3 remained unchanged. Thus, in girls with Turner's syndrome, estrogen replacement
      by the transdermal route may have less deleterious effect on hepatic metabolism
      than oral estrogen.

PMID- 7584705
TI  - Long term treatment with low dose testosterone in constitutional delay of growth
      and puberty: effect on bone age maturation and pubertal progression.
AB  - We compared the effects of long term low dose treatment with testosterone on
      pubertal growth and sexual development in boys with constitutional delay of
      growth and puberty (CDGP). We treated 24 boys with intramuscular monthly
      injections with low dose testosterone enanthate (33-50 mg) for 20 months, at a
      chronological age of 14.5 +/- 1.0 years and SDS height of -3.31 and compared
      their response to a group of 14 control boys. Treated patients showed an earlier
      and significant increase in height velocity compared to controls, 10.1 vs 4.0
      cm/year, while the latter group showed their growth spurt twelve months later.
      Both groups showed an initial acceleration in bone age without impairment of
      predicted adult height. During the first 12 months of treatment the increment of
      testicular volume in the treated patients was slightly slower than controls;
      however the earlier the puberty, the slower the testicular increment compared to
      controls. We conclude that treatment of boys with constitutional delay of growth
      with low dose testosterone is effective in improving their height velocity
      without impairment of predicted final height. Progression of testicular volume
      during treatment in some patients is more delayed; however, after treatment it
      increased normally.

PMID- 7584707
TI  - Familial blepharophimosis: an uncommon marker of ovarian dysgenesis.
AB  - We report on six young female patients from two families who were found to have a
      very rare form of ovarian failure. Hypogonadism is inherited with an ocular
      abnormality consisting of a congenital dysplasia of the eyelids. In one family
      inheritance is autosomal dominant and in the other it is a de novo mutation. The
      patients have no other dysmorphic features and are of normal intelligence. Plasma
      levels of follicle-stimulating and luteinizing hormones are significantly
      elevated. Examination of the internal genitalia by laparoscopy was performed in
      four cases with ovarian biopsy in one case; the results are compatible with
      gonadal dysgenesis. Cytogenetic studies indicate the absence of chromosomal
      defects.

PMID- 7584706
TI  - Goiter prevalence in children immigrating from an endemic goiter area in Ethiopia
      to Israel.
AB  - A survey study was performed to assess the prevalence of goiter and thyroid
      dysfunction in a population of 534 Ethiopian children, one year after arrival in
      Israel. The overall prevalence of goiter was 43.6%. Children in the age group 1-2
      years had the lowest prevalence of goiter (6.7%). A progressive increase in
      goiter prevalence and size with age was observed, with peak occurrence around
      puberty for both boys (56.7%) and girls (72.2%). Serum FT4 levels were elevated
      in 4 children; elevated serum TSH levels (above 4.5 mIU/l) were found in 11
      children, all of them had normal FT4 levels. Thus the prevalence of
      hypothyroidism and hyperthyroidism was 2% and 0.8%, respectively, with an even
      distribution across the various age groups. All the children were clinically
      normal. The high prevalence of goiter in this group of Ethiopian children with
      the low frequency of hypothyroidism may be attributed to the combined effects of
      food goitrogens and iodine deficiency prevailing in Ethiopia. The standard
      Israeli diet seems to be adequate in respect to iodine requirements, and no
      iodine enrichment is needed for children immigrating from Ethiopia.

PMID- 7584710
TI  - Pituitary adenomas in childhood and adolescence.

PMID- 7584709
TI  - Pituitary abscess: an unusual presentation of "aseptic meningitis".
AB  - Granulomatous inflammation of the pituitary and pituitary abscesses are rare
      entities. These conditions are found even more rarely in the pediatric aged
      population. We report a case of a radiographic and clinical, sterile pituitary
      abscess with non-caseating granulomatous inflammation in a girl who presented
      with hypopituitarism, meningeal irritation, and symptoms of pituitary apoplexy.

PMID- 7584711
TI  - Growth outcome of "normal" short children who are retarded in skeletal
      maturation.
AB  - The growth and adult stature of "short normal slow maturing" children (SNSMC)
      have not been adequately studied. We applied a well-known adult stature
      prediction method to SNSMC and average children (AC). The accuracy of adult
      stature prediction in SNSMC warranted its use as a guide to the effectiveness of
      treatment (average median absolute errors: 1.71 cm males, 1.61 cm females).
      Additionally, we derived biological parameters from the serial statures for SNSMC
      and AC. Several of the biological parameters differed significantly between the
      SNSMC and AC in both sexes (stature velocity and age at onset of the pubescent
      spurt, age at peak height velocity, and the increment in stature from peak height
      velocity to 18 years) and the differences between these groups in stature at
      onset of the pubescent spurt and at peak height velocity were significant for
      males. The differences were not significant in either sex for the rate of growth
      at peak height velocity or the increase in stature from the onset of the
      pubescent spurt to peak height velocity.

PMID- 7584713
TI  - [Recent progress in development of psychotropic drugs (2)--antipsychotics].
AB  - The discovery of chlorpromazine led to rapid progress in drug therapy for
      schizophrenia. However, conventional neuroleptics frequently induce EPS and
      tardive dyskinesia in addition to the drawback of having little effect against
      negative symptoms. New types of atypical antipsychotics has been actively
      developed in Japan to overcome these drawbacks. Firstly, serotonin-dopamine
      antagonist (SDA) is most actively developed. Eight SDAs have been introduced into
      clinical trials: risperidone's trials have been finished and a NDA has been
      filed, Org 5222 has been dropped because of worsening of significant cases, and 6
      SDAs (SM-9018, sertindole, seroquel, AD-5423, ziprasidone and olanzapine) are now
      under development. Secondly, OPC-14597, a unique atypical antipsychotic has been
      advanced to the phase 3 study, which has both DA autoreceptor-agonistic and D2
      receptor blocking actions. Thirdly, we have much interest in NE-100, a selective
      sigma receptor antagonist which potently suppresses the phencyclidine-induced
      behaviors. Finally. a 5-HT3 receptor antagonist, alosetron was already dropped
      because it showed no antipsychotic effects, although it was introduced with great
      expectations. We hope that as many as possible new antipsychotics will be
      approved for the battle against schizophrenia.

PMID- 7584708
TI  - Estrogen and diclofenac sodium therapy in a prepubertal female with idiopathic
      juvenile osteoporosis.

PMID- 7584715
TI  - [Assessment of anxiolytics (3)--biochemical approach].
AB  - Synaptoneurosomes are entities in which a presynaptic sac (synaptosome) is
      attached to a resealed postsynaptic vesicle (neurosome). Biochemical studies have
      demonstrated that the synaptoneurosomes retain several receptor-mediated
      activities such as accumulations of cyclic AMP and ion fluxes. GABAA receptor
      mediated 36Cl- uptake and modulatory effects of the uptake by benzodiazepines,
      barbiturates and neurosteroids have been reported in rat brain synaptoneurosomes.
      The in vitro protocol of the GABAA receptor ligand-stimulated 36Cl- influx proves
      to be of value for the screening of new compounds such as anxiolytics.

PMID- 7584712
TI  - Facilitation of the growth promoting effect of growth hormone (GH) by an antibody
      to methionyl-GH.
AB  - Despite the development of antibodies to methionyl growth hormone in a child with
      hypopituitarism, the patient grew at a rapid rate on low doses of somatotropin.
      Serum immunoglobulins from this patient stimulated the growth of Nb2 lymphoma
      cells in vitro in samples obtained within 48 hours after the last dose of growth
      hormone, while samples obtained several weeks after an injection of methionyl
      growth hormone did not. Immunoglobulins from normal subjects or from
      hyposomatotropic patients being treated with methionyl growth hormone who had not
      developed antibodies did not stimulate Nb2 lymphoma cell growth. We suggest that
      the antibodies to methionyl growth hormone in this child served as a reservoir
      for exogenous growth hormone or facilitated the interaction of growth hormone
      with the prolactin receptor on the Nb2 lymphoma cell.

PMID- 7584714
TI  - [The assessment of drug effects on memory in animals].
AB  - The methodology of experiments on animal memory for the preclinical evaluation of
      cognition enhancers was reviewed. Representative experiments such as passive
      avoidance, the radial-arm maze, and delayed response are described. From the
      viewpoint of the predictability of drug effects in humans, the usefulness and the
      problems associated with these experiments are discussed. For example, such
      problems as the significance of response latency in the passive avoidance
      experiment, the innate robustness of the behavior in the radial-arm maze
      experiment, and the stability of the behavioral baseline in the delayed response
      experiment were noted. As for future directions, three issues are proposed: the
      importance of the descriptive principle in evaluating the data, the systematic
      construction of the testing battery, and the need for the development of new
      experimental methods that simulate human memory disorders.

PMID- 7584716
TI  - Relation between age-related changes in hyper-emotionality and serotonergic
      neuronal activities in the rat limbic system.
AB  - To examine the relationship between higher concentrations of 5-HT and 5-HIAA in
      the aged rat brain and their hyper-emotionality, behavioral and neurochemical
      studies were performed. In the behavioral studies, under novel circumstances, the
      aged rats showed an significant increase in defecation. Furthermore, their
      locomotor activity was much less than that of young rats, and the numbers of head
      dips of aged rats were significantly decreased compared to those of young rats.
      In the neurochemical studies, the concentrations of 5-HT and 5-HIAA in the limbic
      system (e.g., hippocampus, amygdala and septal area) of aged rats were much
      higher than those of young rats (P < 0.001) under normal conditions. The
      possibility that the hyper-emotionality of aged rats might be related to the
      hyper-activities of serotonergic neurons in their limbic system were taken into
      consideration when the results were analyzed.

PMID- 7584719
TI  - Haloperidol and restraint differently inhibit the induction of sensitization to
      the ambulation-increasing effect of methamphetamine in mice.
AB  - Haloperidol (HPD: 0.4 mg/kg, sc) completely abolished not only the ambulatory
      stimulation by methamphetamine (MAP: 2 mg/kg, sc) but also the induction and
      expression of MAP sensitization in the combined administration schedule. HPD also
      significantly reduced the induction of MAP sensitization when the mice were
      treated with HPD at 1/12, 1/4, 1, 2, 3, 4 or 5 hr but not at 1/2 hr or later than
      6 hr, after each administration of MAP. The inhibition by the 3-hr post-treatment
      with HPD was as strong as that by the combined administration. On the other hand,
      a restraint of abulation for 3 hr (putting the mouse in a small jar)
      significantly inhibited the induction of MAP sensitization when it was started at
      0/4 hr, but not at 1/2-6 hr, after each MAP administration. The inhibitory
      effects of restraint, starting at 0-1/4 hr, were almost equivalent to those of
      the post-treatments with HPD at the same times. The post treatments with HPD +
      restraint showed similar inhibitory effects on MAP sensitization to those of HPD
      alone. The repeated administration of saline together with post-treatment with
      either HPD, restraint or HPD + restraint did not change MAP sensitivity. These
      results suggest that a couple of free movement in the activity cage and
      stimulation of dopamine receptors for longer than 1/2 hr immediately after
      administration of MAP, and an agonistic effect on dopamine receptors during 1-5
      hr after MAP are responsible for perfect induction of the MAP sensitization in
      terms of ambulation in mice.

PMID- 7584718
TI  - [Behavioral effects of chronic apomorphine, and D-1/D-2 dopamine receptor
      activities in rats].
AB  - The present study was conducted to investigate the effects of chronic treatment
      with apomorphine on yawning and stereotyped behaviors induced by apomorphine, and
      catalepic responses induced by haloperidol. Rats received apomorphine (1 mg/kg,
      sc), a direct dopamine D1/D2 agonist, or vehicle once a day for 21 days. The
      chronic treatment with apomorphine shifted to the right the dose response curve
      of yawning to administration of apomorphine, which preferentially activates
      presynaptic dopamine D-2 receptors (auto receptors) at low doses. Haloperidol
      (0.5 mg/kg, ip)-induced catalepsy mediated by the inhibition of postsynaptic D-2
      receptors was unaltered. A subsequent challenge dose of apomorphine (5 mg/kg, ip)
      produced oral stereotyped behaviors such as sniffing, licking and biting in the
      vehicle-treated rats. Chronic apomorphine treatment produced significant
      enhancement of sniffing alone, which may be behavioral sensitization to
      apomorphine, and, in contrast, attenuated licking and biting, which depend on D-2
      receptor activities. These phenomena lasted for at least 30 days. Sniffing might
      involve relatively increased stimulation of D-1 receptors, as compared with
      licking and biting. These results suggest that chronic apomorphine reduces
      presynaptic dopamine D-2 receptor activity, and as a consequence may induce long
      lasting postsynaptic dopamine receptor (mainly D-1 receptor) activation.

PMID- 7584720
TI  - [Changes in GABAA/benzodiazepine receptor complex function in the pentobarbital
      dependent rat].
AB  - Changes in GABAA receptor function were studied in pentobarbital (PB)-dependent
      rats. Physical dependence on PB in male Lewis rats was induced by the drug
      admixed food method. The 36Cl- influx into cerebral cortical synaptoneurosomes
      induced by 10 microM GABA in the PB-dependent rat was significantly decreased
      compared with the control. The enhancement of GABA-dependent 36Cl- influx by the
      addition of PB, ethanol (EtOH) and flunitrazepam (FZ) was not recognized in the
      PB-dependent group. The addition of picrotoxin and bicuculline had no effect on
      GABA-dependent 36Cl- influx in PB-dependent rats. In the [3H]muscimol binding
      assay of low affinity sites of the GABAA receptor, Kd was significantly increased
      and Bmax was significantly decreased in PB-dependent rats compared with the
      control. However, these values were similar between PB-dependent and control rats
      in the study of [3H]FZ binding to benzodiazepine (BZ) receptors. The present
      study indicates that GABAergic transmission involving GABA-dependent chloride
      channels was altered in PB dependent rats. This alteration of the
      GABAA/BZ/chloride channel complex function may be related to the cross-tolerance
      among barbiturates, BZ and EtOH.

PMID- 7584722
TI  - [Control mechanisms of locomotor movements from a viewpoint of behavioral
      control].
AB  - Locomotor movements are generally considered to be established by integrating the
      activities of the neuronal mechanisms related to each of the "automatic" and
      "volitional" control. As one of the neuronal mechanisms contributing to such
      integration, the possible roles played by the ponto-medullary reticular formation
      have recently been reexamined. As is well established, cells in the ponto
      medullary reticular formation are related to arousal behavior, and the reticular
      formation itself is one of the major sources for generalized motor drive. In
      intact, awake cats, electrical stimulation delivered directly or indirectly to
      the reticular formation can evoke locomotor movements accompanied by an "alerting
      response" and preceded by postural adjustments adequate for locomotion.
      Microinjection of bethanechol, a short-acting cholinergic agonist, into the
      pontine reticular formation results in a peculiar modification of posture and, as
      a consequence, locomotor movements, even changing the arousal level of the
      animals. The cats with bilateral tegmental lesions in the pons exhibit locomotor
      movements during a state of rapid eye movement sleep without atonia. It is
      conceivable that the ponto-medullary reticular formation contributes greatly to
      the integration of neuronal activities related to automatic and volitional
      control of locomotor movements so as to establish a goal-directed behavioral
      locomotor movement.

PMID- 7584721
TI  - [Midkine in relation to development and pathological status of the nervous
      system].
AB  - Midkine (MK) is a novel heparin-binding growth factor whose expression is
      regulated by retinoic acid. Midkine is structurally unrelated to other growth
      factors, and together with pleiotrophin (PTN) subsequently cloned forms a new
      family of growth factors. Midkine enhances neurite outgrowth and survival of
      several embryonic neurons. Midkine mRNA is strongly expressed in the nervous
      system during the midgestation period, while the normal adult brain scarcely
      expresses it. Immunohistochemical studies revealed midkine localization beside
      radial glial processes along which neurons migrate. Upon experimental brain
      infarction in the rat, midkine expression in the ischemic region begins as early
      as 1 day after the operation. Senile plaques of patients with Alzheimer's disease
      invariability express midkine. These findings indicate that midkine plays
      significant roles both in the formation and repair of the central nervous system
      and processes leading to its diseases.

PMID- 7584717
TI  - Inhibitory effects of newly synthesized Ser-contained GABA-peptides administered
      into either caudate putamen or amygdala on methamphetamine-induced hyperactivity.
AB  - The locomotor activities induced by methamphetamine (MAP: 1 mg/kg) following the
      microinjection of either GABA or three synthesized GABA-peptides (PLG, PSLG,
      PDSLG) into the rat caudate putamen or the amygdala were measured by using
      behavioral analysis. The ip administration of MAP induced hyperactivities in a
      time-dependent manner, and the maximum activity was measured 30 min after MAP
      administration. This hyperactivity was observed for more than 2 hrs. By the
      microinjection of GABA-peptides (0.054-540 nmol) into each brain region, the MAP
      induced hyperactivity was significantly reduced in a dose-dependent manner,
      although the single administration of examined dosages of these peptides did not
      influence the locomotor activity. In the case of microinjection of GABA into
      either one of the brain regions, only the larger dosage (27,000 nmol)
      significantly reduced the MAP-induced hyperactivity, whereas this inhibition was
      less than that seen at the dose of 540 nmol of GABA-peptides. Furthermore, the
      microinjection of newly synthesized GABA-peptides, PSLG and PDSLG, into the
      caudate putamen was more effective than those obtained by injection into the
      amygdala. However, either microinjection of PLG or GABA into both regions showed
      similar inhibition. These results suggest that the pharmacological properties of
      newly synthesized GABA-peptides are different compared to those of PLG and GABA,
      and that these differences might be due to the primary inhibitory effects of the
      serine-contained GABA-peptides on dopaminergic neuronal activity, but not on GABA
      neurons.

PMID- 7584723
TI  - [Dystrophin, dystrophin-associated protein and dystrophinopathy].
AB  - Dystrophin is a protein product of the gene responsible for Duchenne muscular
      dystrophy (DMD), and is a long slender protein localized at the protoplasmic
      surface of sarcolemma. Dystrophin binds with actin filaments at its amino
      terminal region, and with dystrophin-associated proteins (DAPs) at its carboxyl
      terminal region. DAPs are composed of a glycoprotein complex and a syntrophin
      complex, a complex of proteins binding with dystrophin and located
      intracellularly. Glycoprotein complex is composed of dystroglycan complex and
      sarcoglycan complex, both of which are membrane-integrated. Dystrophin binds with
      dystroglycan complex which transverse through sarcolemma and then binds with
      laminin in the basal lamina, forming a long axis between action threads and the
      extracellular matrix. Sarcoglycan complex does not directly bind with dystrophin
      but binds with dystroglycan complex. Disruption of the axis results in dystrophic
      changes in one kind of congenital muscular dystrophy (CMD). Loss of the
      sarcoglycan complex gives rise to childhood severe autosomal recessive muscular
      dystrophy (SCARMD) which is clinically very similar to DMD. In DMD, the
      sarcoglycan complex is mostly lost, and the axis is for the most part defective.
      Therefore, it is likely that the causes of DMD and SCARMD may be similar and may
      be modified by the mechanism which gives rise to CMD.

PMID- 7584724
TI  - [Assessment of anxiolytics (4)--Social interaction test].
AB  - The rat social interaction test is based on spontaneous social interaction
      behaviors, such as sniffing and following between two rats, and thus does not
      necessitate noxious food or water deprivation, electric shocks and lengthy
      training. The amount of time that pairs of rats spent interacting with each other
      varied systematically with the environmental stimuli, such as the illumination
      and familiarity of the test arena. When tested under the most aversive high
      light: unfamiliar condition, control subjects exhibited low levels of social
      interaction. Acute treatment with benzodiazepine-related agents exerted
      anxiolytic effects, as measured by an increase in the time spent by pairs of rats
      engaged in social interaction, while anxiogenic agents decreased social
      interaction under the same high light: unfamiliar condition. The minimum
      effective doses of benzodiazepine-related agents in this paradigm corresponded
      well to their respective clinical dosages. Thus, the simple social interaction
      test is beneficial in assessing effects of agents on the anxiety states of
      animals in a qualitative and quantitative manner. Treatment with 5-HT-related
      anxiolytic agents also increased social interaction. However, there existed some
      differences in the magnitude of increases or characteristics of each behavioral
      component between benzodiazepine- and 5-HT-related agents, which were consistent
      with the clinical literature regarding their efficacy in the treatment of anxiety
      disorders. Therefore, the rat social interaction test is predictable for clinical
      anxiolytic effects of non-benzodiazepine agents in comparison with
      benzodiazepines.

PMID- 7584726
TI  - Evaluation of acute and sub-acute effects of cocaine by means of circadian
      variation in wheel-running and drinking in mice.
AB  - The effects of cocaine on wheel-running and drinking activities in mice, housed
      under a 12-h light-dark schedule (lighted period; 6:00-18:00 h), were
      investigated through long continuous observation. Cocaine (20 and 40 mg/kg, sc),
      administered at 11:00 h, acutely increased wheel-running and drinking, but it was
      followed by a sub-acute suppression of the spontaneous increment in both of these
      behaviors during the coming dark period (18:00-6:00 h). Such behavioral
      accelerating and suppressing effects of cocaine did not change throughout the
      whole course of administration, which was repeated five times at 3- to 5-day
      intervals. In addition to these findings, wheel-running and drinking
      spontaneously increased during the light period and decreased during the dark
      period on the day after the drug administration. On the other hand, the repeated
      administration of cocaine at 18:00 h never increased, but rather acutely
      suppressed both behaviors during the dark period, and no trends in the behavioral
      changes on the next day were clearly shown. These results suggest that the
      effects of cocaine on wheel-running and drinking differ depending on the time of
      day of the administration.

PMID- 7584727
TI  - [Increase in extracellular levels of serotonin and amino acids in the rat brain
      following cyanide-induced energy failure].
AB  - We studied the effects of ATP depletion on neurotransmitter release in the rat
      brain using the microdialysis method. Ringer's solution containing 2 mM sodium
      cyanide (NaCN) was perfused into the hippocampus and striatum for 60 min via a
      microdialysis probe, and changes in serotonin (5-HT) and amino acids (glutamate,
      aspartate and taurine) levels in dialysates were investigated. NaCN perfusion
      induced a transient 3.9-fold increase in 5-HT levels in the hippocampal
      dialysate. Amino acid levels in dialysates also increased during NaCN perfusion,
      but differently in the striatum and hippocampus (glutamate: 1.3- and 2.4-fold,
      taurine: 2.3- and 1.3-fold, respectively). Perfusion of Ca(2+)-free Ringer's
      solution remarkably suppressed the NaCN-induced increase in 5-HT but not the
      increases in amino acid levels. Depolarization by 100 mM KCl perfusion could
      induce increases in 5-HT and amino acids in dialysates at 3 hr after NaCN
      perfusion similarly with that of control. These findings indicate that the
      sensitivity of nerve terminals to energy failure are different between neurons
      containing different neurotransmitters and also between brain regions, and
      suggest that this regionally different sensitivity of amino acid neurons might be
      involved in the underlying mechanism of the localized vulnerability to transient
      ischemia.

PMID- 7584728
TI  - [Chronic treatment with nicotine enhances the sensitivity of dopamine
      autoreceptors that modulate dopamine release from the rat striatum].
AB  - This study was undertaken to investigate the effect of chronic nicotine treatment
      on electrically evoked dopamine (DA) release from striatal slices and locomotor
      activity in rats under the influence of DA autoreceptor agonists and antagonist.
      Nicotine was supplied chronically by Alzet osmotic minipump for two weeks. B
      HT920 and quinpirole decreased and (-)-sulpiride increased the evoked DA release
      from striatal slices. The B-HT920 and quinpirole-induced decrease and the (-)
      sulpiride-induced increase in evoked DA release were enhanced by chronic
      treatment with nicotine. Nicotine itself has little effect on the evoked DA
      release. B-HT920 and quinpirole decreased and (-)-sulpiride, methamphetamine and
      apomorphine increased the locomotor activity in the rat. The B-HT920 and
      quinpirole-induced decrease and the (-)-sulpiride-induced increase in locomotor
      activity were enhanced by chronic treatment with nicotine. On the other hand, the
      methamphetamine and apomorphine-induced increase in locomotor activity were
      unaltered by chronic treatment with nicotine. Chronic nicotine treatment itself
      has no effect on locomotor activity. These data indicate that chronic treatment
      with nicotine caused a supersensitivity in presynaptic DA autoreceptors that
      modulate DA release from DA terminals in the rat striatum, and no change in the
      function of postsynaptic DA receptors.

PMID- 7584730
TI  - [Study of zopiclone with quantitative EEG analysis and topography].
AB  - Zopiclone is a cyclopyrrolone derivative which possesses hypnotic activity. This
      drug is known to increase the slow sleep stage compared to benzodiazepines in
      polysomnography. The subjects were 10 right-handed healthy male volunteers aged
      21-23 years. Double-blind crossover trials with placebo control were conducted in
      a random sequence at intervals of 1 week. Zopiclone 7.5 mg and placebo were
      administered as single oral doses. Three-minute vigilance controlled EEGs at
      before and at 1, 3, and 5 h after drug administration, and the response times
      were recorded. One minute out of the 3-minute EEGs was analyzed with FFT and the
      power spectrum was obtained. Then the absolute amplitude power (microV) was
      calculated. These results were subjected to Student's t-test (double difference)
      and displayed with topographic maps (t statistic significance probability
      mapping). Zopiclone prolonged the latency of the response time, and increased the
      amount of delta absolute amplitude power over the right central region, beta 1
      absolute amplitude power over the left central region and beta 2 absolute
      amplitude power over the right central area along with decreased alpha absolute
      amplitude power over the occipital region and theta power over the left frontal
      pole area after 1 h, when the peak pharmacological effect was expected. The EEG
      profiles of zopiclone were different from that of diazepam reported previously
      concerning the increase in delta activity.

PMID- 7584729
TI  - [Changes in GABAA/benzodiazepine receptor complex function in the pentobarbital
      dependent rat. II: Strain differences between Lewis and Wistar-Kyoto rats].
AB  - We studied the differences in alterations of GABAAergic receptor function between
      pentobarbital (PB)-dependent female Lewis (LEW) and Wistar-Kyoto (WKY) rats. The
      36Cl- influx induced by 10 microM GABA in the PB-dependent WKY was significantly
      lower than that in the control, while there was no significant 36Cl- influx
      change in both PB-dependent and control LEW. The additions of PB, flunitrazepam
      (FZ) and ethanol (EtOH) enhanced the GABA-dependent 36Cl- influx in control rats
      of both strains. However, the enhancements of 36Cl- influx by PB, FZ, EtOH were
      not recognized in PB-dependent WKY. On the other hand, the enhancement of GABA
      dependent 36Cl- influx was observed only with the addition of PB in PB-dependent
      LEW. The additions of bicuculline (BIC) and picrotoxin (PIC) inhibited GABA
      dependent 36Cl- influx in control rats of both strains. However, inhibition of
      36Cl- influx by BIC and PIC was not recognized in the PB-dependent WKY. These
      results suggest that physical dependence on PB in WKY may cause greater
      functional alterations of the GABA/benzodiazepine receptor complex than those in
      LEW, and that these changes in this receptor complex may relate to the difference
      in the development of physical dependence on PB between the two strains.

PMID- 7584725
TI  - [Assessment of anxiolytics (5)--Vogel-type conflict task in mice].
AB  - The Vogel-type conflict task, in which drinking of water by animals is punished
      by electric shock, is well known as a simple conflict procedure, and has come
      into wide use. This task has almost been established in rats. On the other hand,
      there are only few reports about application of the task to mice, and such
      studies have not proceeded smoothly. This report presents technical problems in
      the application of the task to mice based on various experiments, in which
      experimental conditions such as procedures, intensity of electric shock and mouse
      strain differed, in order to determine the anti-conflict action of diazepam (DZ).
      These experiments showed that successful detection of DZ action depended upon the
      experimental conditions. Therefore, experimental designs are important in
      evaluating anti-conflict action of chemicals in the Vogel-type task in mice.

PMID- 7584731
TI  - Spontaneous recurrence of methamphetamine psychosis: process and monoamine
      neurotransmitter function.
AB  - We studied the process that causes a spontaneous recurrence of methamphetamine
      (MAP) psychosis, a phenomenon known as flashbacks, in 41 female flashbackers by a
      comparison of clinical characteristics between the 41 flashbackers and 87 non
      flashbackers with previous MAP psychosis. We evaluated plasma levels of monoamine
      metabolites in 25 of the 41 flashbackers, 19 of the 87 non-flashbackers, 9 female
      patients with persistent MAP psychosis and 61 physically healthy female controls.
      All 41 flashbackers had experienced a significantly greater frequency of
      threatening events and threatening paranoid-hallucinatory states than the 87 non
      flashbackers during previous MAP abuse. The triggering factor was a mild fear of
      other persons due to the evocation of frightening images, encoded through
      threatening experiences during previous MAP abuse. Norepinephrine (NE) levels
      were significantly associated with a history of flashbacks. Plasma 3-methoxy-4
      hydroxyphenylglycol (MHPG) levels were significantly higher during flashbacks and
      during periods of normalcy in the flashbackers, and in the non-flashbackers, than
      MHPG levels in the user controls. NE levels in the patients with persistent MAP
      psychosis were also significantly higher than NE levels in the user controls.
      Elevated NE levels in the flashbackers were associated with disrupted NE, 5-HT
      and DA turnover. Thus, MAP-induced sensitization to frightening images may have
      caused the flashbacks due to aggravated noradrenergic hyperactivity.

PMID- 7584732
TI  - Aseptic tenosynovitis of the digital flexor tendon sheath, fetlock and pastern
      annular ligament constriction.
AB  - The anatomy of the digital flexor tendon sheath and related tendons and ligaments
      is described. Diagnosis and management of acute tenosynovitis and long-term
      tenosynovitis and associated tendon injuries are discussed, as well as the
      syndrome of stenosis of the fetlock canal (or fetlock annular ligament
      constriction) and palmar annular ligament constriction. Desmitis of the palmar
      annular ligament is also described.

PMID- 7584735
TI  - Tendon, tendon sheath, and ligament injuries in the pastern.
AB  - The palmar (plantar) aspect of the pastern is an anatomically complex area and an
      understanding of this is a prerequisite for accurate diagnosis of injuries in
      this area. The gross and normal ultrasonographic anatomy are described, and
      injuries of the superficial and deep digital flexor tendons and the digital
      flexor tendon sheath, the distal sesamoidean ligaments, and the palmar ligaments
      of the proximal interphalangeal joint are discussed.

PMID- 7584733
TI  - Infectious tenosynovitis.
AB  - Infectious tenosynovitis is treated similarly to infectious arthritis. The
      principles of treatment include an early diagnosis and immediate therapy. Therapy
      should include use of systemic and local antimicrobials and sheath lavage and
      drainage. Fibrosis and adhesions can be minimized with passive range of motion
      exercises, intrathecal hyaluronate, and phenylbutazone therapy. Restrictive
      fibrosis may be treated successfully by annular ligament resection.

PMID- 7584734
TI  - Suspensory ligament desmitis.
AB  - The gross and functional anatomy of the suspensory ligament (SL) and its
      ultrasonographic variability are described. Injuries of the suspensory apparatus
      are divided into lesions confined to the proximal one third of the metacarpus or
      metatarsus (proximal suspensory desmitis and avulsion fractures), lesions of the
      body, and branch lesions. Complete breakdown injuries are also discussed. In view
      of the close association of the SL, the second, third, and fourth metacarpal or
      metatarsal bones, and the proximal sesamoid bones, associated bony lesions are
      also considered.

PMID- 7584738
TI  - Tendon lacerations.
AB  - Early and appropriate therapy for tendon lacerations can result in a sound,
      athletic horse in more than 50% of cases. Extensor tendon lacerations have a
      better prognosis and wound care, immobilization, and protection from flexor
      dominance are the goals of therapy. Flexor tendon lacerations are more serious
      because of the loss of support to the limb. Therapy goals include wound care,
      tendon suturing, and strict immobilization for approximately 6 weeks. This
      article describes management of horses with tendon lacerations and the outcomes
      in detail.

PMID- 7584737
TI  - Ligaments associated with joints.
AB  - This article contains a short introduction to the anatomy, physiology, and
      pathophysiology of ligaments associated with diarthrodial joints. Individual
      ligaments are discussed on a regional basis as forelimb, distal limb, and
      hindlimb. Emphasis is placed on the anatomy of the ligaments because this is the
      key to sound clinical application of their involvement in joint disease. There
      are few conditions of diarthrodial joints that do not involve their associated
      ligaments, and this role may be in causative, diagnostic, and therapeutic or
      convalescent considerations.

PMID- 7584736
TI  - Soft tissue injuries of the tarsus.
AB  - Contrast radiography provides a clear survey of the size, shape, and location of
      extratendovaginal fluid-filled cavities, distended bursa, and tendon sheaths and
      demonstrates intersynovial communication. Ultrasonography effectively
      demonstrates Achilles tendon injury, slippage of the SDFT off the summit of the
      calcaneus, assorted ligamentous injuries, and cystic or solid extratendovaginal
      masses. It will also demonstrate distended bursae and tendon sheaths, but it is
      not as effective in demonstrating a synovial herniation, or a narrow synovial
      fistula. Contrast radiography may prove to be the imaging modality of choice for
      examination of fluctuating swellings, whereas ultrasonography is preferred for
      the assessment of firm swellings. Routine radiographic evaluation in the clinical
      assessment of soft tissue injuries in the hock region continues to play an
      invaluable diagnostic role.

PMID- 7584740
TI  - Old and vulnerable in the emergency department.

PMID- 7584739
TI  - Miscellaneous conditions of tendons, tendon sheaths, and ligaments.
AB  - The use of diagnostic ultrasonography has greatly enhances our ability to
      diagnose injuries of tendons and tendon sheaths that were previously either
      unrecognized or poorly understood. For may of these injuries, there is currently
      only a small amount of follow-up data. This article considers injuries of the
      deep digital flexor tendon and its accessory ligament, the carpal tunnel syndrome
      soft tissue swellings on the dorsal aspect of the carpus, intertubercular
      (bicipital) bursitis and bicipital tendinitis, injuries of the gastrocnemius
      tendon, common calcaneal tendinitis, rupture of peroneus (fibularis tertius) and
      ligaments injuries of the back.

PMID- 7584741
TI  - Cardiopulmonary resuscitation research models: motherboards, mammals, and man.

PMID- 7584742
TI  - Economics of "Fast-track" centers.

PMID- 7584743
TI  - Compression rates in cardiopulmonary resuscitation: how fast is fast enough?

PMID- 7584744
TI  - Biochemical markers of cerebral injury in patients with minor head trauma and
      ethanol intoxication.
AB  - OBJECTIVE: To determine whether biochemical markers can selectively identify
      those intoxicated patients with presumed minor head injuries who are likely to
      have CT evidence of intracranial injury. METHODS: Patients presenting to the ED
      with simultaneous presumed minor head trauma and ethanol intoxication were
      prospectively entered into this cross-sectional study. Following phlebotomy, all
      patients received cranial CT. Associations between the presence of an abnormal CT
      scan for injury and serum levels of the following biochemical markers were
      sought: serum catecholamines, creatine kinase-brain band (CK-BB), and serum
      amylase. Serum levels are reported as mean +/- SEM. RESULTS: Nine of the 107
      patients (8.4%; 95% CI 3.9-15.4%) had evidence of intracranial injury on CT. Mean
      serum CK-BB (16.1 +/- 3.7 vs 13.2 +/- 9.6 ng/mL), serum norepinephrine (913 +/-
      117 vs 1,089 +/- 76 pg/mL), and serum amylase (64.9 +/- 14.8 vs 84 +/- 4.7 U/L)
      levels were not significantly different in patients with and without CT evidence
      of intracranial injury, respectively. Mean serum epinephrine (298 +/- 54 vs 167
      +/- 18 pg/mL; p = 0.03) and serum dopamine (218 +/- 50 vs 130 +/- 9 pg/mL; p =
      0.014) levels were significantly elevated in the group with intracranial injury
      on CT. A threshold level of serum dopamine > or = 140 pg/mL yields a sensitivity
      of 89% (95% CI 52-100%) and a specificity of 80% (95% CI 70-87%) for CT-evident
      injury. A threshold level of serum epinephrine > or = 218 pg/mL yields a
      sensitivity of 89% (95% CI 52-100%) and a specificity of 80% (95% CI 70-87%) for
      CT-evident injury. CONCLUSION: Elevated serum epinephrine and dopamine levels are
      associated with intracranial CT-evident injury for ethanol-intoxicated patients
      with presumed minor head injuries. The potential use of these biochemical markers
      to guide a more selective approach to cranial CT scanning warrants further
      evaluation.

PMID- 7584745
TI  - Effect of delayed treatment with sodium polystyrene sulfonate on serum lithium
      concentrations in mice.
AB  - OBJECTIVES: To determine the efficacy of sodium polystyrene sulfonate (SPS) in
      lowering serum lithium (Li) concentrations. Specifically, to determine the
      effects of both different doses of SPS and different times to treatment with SPS
      on serum Li levels. METHODS: The study was a controlled, single-dose murine trial
      of SPS on serum Li levels. Male CD-1 mice (n = 525) were given orogastric LiCl
      and then divided into three main treatment groups: group SPS received a single
      orogastric administration of SPS in a dose of 5 gm/kg body weight at either 0,
      15, 30, 45, or 90 minutes after LiCl; group half-SPS received a single orogastric
      administration of SPS in a dose of 2.5 gm/kg body weight at times equivalent to
      those of group SPS; and the control group received orogastric deionized water in
      a volume equivalent to that of group SPS at 0, 15, 30, 45, or 90 minutes after
      LiCl. Subgroups of seven to ten mice in each of the four treatment groups were
      sacrificed at one, two, four, and eight hours after administration of LiCl, and
      their blood was analyzed for Li concentration. RESULTS: 1) Single doses of SPS
      significantly lowered serum Li concentrations; 2) this effect was dose-related;
      3) the delays in administration of SPS used in this study did not significantly
      reduce its ability to lower serum Li concentrations; and 4) even when
      administered after peak serum Li concentrations had been achieved, a single dose
      of SPS was effective in lowering serum Li levels. CONCLUSIONS: SPS may be
      efficacious in the treatment for Li toxicity under certain circumstances, even
      when there is delay to treatment. Additional study is warranted to further
      characterize the ability of SPS to alter Li kinetics.

PMID- 7584747
TI  - Dehydration and orthostatic vital signs in women with hyperemesis gravidarum.
AB  - OBJECTIVES: To assess the hydration status of women presenting to an ED with
      hyperemesis gravidarum and to determine whether clinically relevant changes in
      orthostatic vital signs occur. METHODS: A convenience sample of 23 pregnant women
      who had hyperemesis gravidarum, with each patient serving as her own control. The
      study took place in the ED observation unit of an urban teaching hospital. Women
      who had pregnancies of < or = 16 week's gestation who had been vomiting for at
      least 24 hours were included. Supine and standing pulse rates and blood pressures
      (BPs) were measured sequentially after 5 minutes in each position. Patient weight
      and urine specific gravity (SG) also were recorded. After 6 L of lactated
      Ringer's solution was infused over a 12-hour period, the same measurements were
      repeated. Pre- and posthydration changes were analyzed using the paired t-test.
      RESULTS: The mean treatment weight gain as a percentage of the total body weight
      was 5.6% +/- 2.2% (mean +/- SD). The urine SG decreased from 1.027 +/- 0.004 to
      1.008 +/- 0.003 (p < 0.001). The mean change in systolic BP upon assuming the
      standing position was -8.3 +/- 12.7 mm Hg before hydration vs 2.9 +/- 7.8 mm Hg
      after hydration (p < 0.001). The corresponding change in mean diastolic BP was
      3.7 +/- 10.9 mm Hg before hydration vs 8.6 +/- 10.9 mm Hg after hydration (p =
      0.12). The mean change in pulse rate upon standing was 26.8 +/- 14.5 beats/min
      before hydration vs 14.5 +/- 10.1 beats/min after hydration (p = 0.002).
      CONCLUSIONS: Women who present to the ED with hyperemesis gravidarum are
      significantly dehydrated and experience measurable improvement in postural pulse
      rate and systolic BP changes with rehydration. However, the presenting
      orthostatic changes lack sufficient sensitivity to be effectively used as
      quantitative screening tests for dehydration.

PMID- 7584746
TI  - Terbutaline vs albuterol for out-of-hospital respiratory distress: randomized,
      double-blind trial.
AB  - OBJECTIVE: To determine the efficacy and safety of single doses of subcutaneous
      terbutaline (TERB) or nebulized albuterol (ALB) during out-of-hospital treatment
      for respiratory distress from asthma or chronic obstructive pulmonary disease.
      METHODS: Patients aged > 18 years who had respiratory distress were enrolled in a
      double-placebo, double-blind, randomized trial. Paramedics measured respiratory
      severity using an empiric score [respiratory rate, wheezing, speech, and peak
      expiratory flow rate (PEFR)], and the patients rated their own respiratory
      distress using a visual analog scale (VAS). The patients received O2 plus ALB
      (2.5 mg) and saline injection (n = 40) or TERB (0.25 mg) and saline aerosol (n =
      43). RESULTS: The groups were similar with respect to age, gender, initial
      empiric scores (median score 9 for both groups), PEFRs (89 +/- 84 L/min, mean +/-
      SD, for ALB vs 97 +/- 84 L/min for TERB), and respiratory distress VAS scores.
      Both groups showed significant improvement in their respiratory distress VAS
      scores by the time of ED arrival. The ALB group had a greater improvement in
      respiratory distress VAS score than did the TERB group (p < 0.05). Empiric
      scores, PEFR scores, and hospital admission frequencies were not significantly
      different. No complication was observed. CONCLUSION: The out-of-hospital
      administration of either aerosolized ALB or subcutaneous TERB reduced respiratory
      severity. Albuterol provided greater subjective improvement in respiratory
      distress.

PMID- 7584750
TI  - Bi-level positive airway pressure support system use in acute congestive heart
      failure: preliminary case series.
AB  - OBJECTIVE: To describe the use of a noninvasive bi-level positive airway pressure
      (PAP) support system for ED patients with acute congestive heart failure (CHF).
      METHODS: Retrospective case series analysis of ED patients presenting with acute
      CHF in imminent need of endotracheal intubation (ETI) managed with a bi-level PAP
      system. The bi-level PAP system was applied at the discretion of the treating
      emergency physician. Management of the bi-level PAP system, including setting of
      inspiratory PAP (IPAP) and expiratory PAP (EPAP), weaning, adjunct pharmacologic
      therapy, and failure of bi-level PAP support, was determined by the treating
      physician. RESULTS: Only two (9%) of 22 patient presentations necessitated ETI.
      The mean duration of bi-level PAP therapy was 7.9 hours. The mean maximum IPAP
      and EPAP settings were 10.8 and 5.8 cm H2O, respectively. Mean intensive care
      unit length of stay (LOS) was 2.4 days, with a median LOS of only 1 day. There
      were three deaths in the series; none were attributed to the bi-level PAP system.
      No technical difficulty with the bi-level PAP system was noted. CONCLUSION:
      Noninvasive pressure support ventilation with a bi-level PAP support system may
      avert ETI in acute CHF patients. This device can be effectively used by ED
      personnel.

PMID- 7584751
TI  - Out-of-hospital ventilation: bag--valve device vs transport ventilator.
AB  - OBJECTIVE: To examine the patterns of out-of-hospital airway management and to
      compare the efficacy of bag-valve ventilation with that of the use of a transport
      ventilator for intubated patients. METHODS: A prospective, nonrandomized,
      convenience sample of 160 patients requiring airway management in the out-of
      hospital urban setting was analyzed. A survey inquiring about airway and
      ventilatory management was completed by emergency medical services (EMS)
      personnel, and arterial blood gas (ABG) samples were obtained within 5 minutes of
      patient arrival in the ED. The ABG parameters were compared for patients grouped
      by different airway techniques and presence or absence of cardiac arrest
      (systolic blood pressure < 50 mm Hg) upon ED presentation. RESULTS: Over a one
      year period, 160 surveys were returned. The majority (62%) of the patients were
      men; the population mean age was 61 +/- 19 years. Presenting ABGs were obtained
      for 76 patients; 17% (13/76) had systemic perfusion and 83% (63/76) were in
      cardiac arrest. There was no difference in ABG parameters between the intubated
      cardiac arrest patients ventilated with a transport ventilator (pH 7.17 +/- 0.17,
      PaCO2 37 +/- 20 torr, and PaO2 257 +/- 142 torr) and those ventilated with a bag
      valve device (pH 7.20 +/- 0.16, PaCO2 42 +/- 21 torr, and PaO2 217 +/- 138 torr).
      The patients ventilated via an esophageal obturator airway (EOA) device had
      impaired gas exchange, compared with the groups who had endotracheal (ET)
      intubation (pH 7.09 +/- 0.13, PaCO2 76 +/- 30 torr, and PaO2 75 +/- 35 torr). The
      intubated patients not in cardiac arrest had similar ABG parameters whether
      ventilated manually with a bag-valve device or with a transport ventilator.
      Endotracheal intubation was successfully accomplished in 93% (123/132) of
      attempted cases. CONCLUSIONS: In this sample, ET intubation was the most
      frequently used airway by EMS providers. When ET intubation was accomplished,
      adequate ventilation could be achieved using either bag-valve ventilation or a
      transport ventilator. Ventilation via the EOA proved inadequate.

PMID- 7584748
TI  - Theoretically optimal duty cycles for chest and abdominal compression during
      external cardiopulmonary resuscitation.
AB  - OBJECTIVE: To use an electronic model of human circulation to compare the
      hemodynamic effects of different durations of chest compression during external
      CPR, both with and without interposed abdominal compression (IAC). METHODS: An
      electrical analog model of human circulation was studied on digital computer
      workstations using SPICE, a general-purpose circuit simulation program. In the
      model the heart and blood vessels were represented as resistive-capacitive
      networks, pressures as voltages, blood flow as electric current, blood inertia as
      inductance, and cardiac and venous valves as diodes. External pressurization of
      the heart and great vessels, as would occur in IAC-CPR, was simulated by the
      alternate application of damped rectangular voltage pulses, first between
      intrathoracic vascular capacitances and ground, and then between intra-abdominal
      vascular capacitances and ground. With this model compression frequencies of 60,
      80, and 100 cycles/min and duty cycles ranging from 10% to 90%, both with and
      without IAC, were compared. RESULTS: There was little difference in hemodynamics
      when the overall compression frequency was varied between 60 and 100 cycles/min,
      but the effects of duty cycle were substantial. During both standard CPR and IAC
      CPR, total flow and coronary flow were greatest at chest compression durations
      equal to 30% of cycle time. Interposed abdominal compression substantially
      improved simulated systemic blood flow and perfusion pressure at all duty cycles,
      compared with standard CPR without abdominal compression. Mean arterial pressure
      > 75 mm Hg and artificial cardiac output > 2.0 L/min could be generated by 30%
      duty cycle compression with IAC. Coronary perfusion in the model is clearly
      optimized at 30% chest compression (i.e., high-impulse chest compression
      technique). CONCLUSION: Combined high-impulse chest compressions and IACs
      maximize blood flow during CPR in the electrical analog model of human
      circulation.

PMID- 7584752
TI  - Padded vs unpadded spine board for cervical spine immobilization.
AB  - OBJECTIVES: To determine whether padding the long spine board improves patient
      comfort, affects cervical spine (c-spine) immobilization, or increases sacral
      transcutaneous O2 tension. METHODS: A prospective randomized, controlled
      crossover study of healthy volunteers was conducted over a two-week period.
      Participants included 30 volunteers with no previous history of c-spine injury or
      disease. The subjects were randomized to either padded or unpadded long spine
      board immobilization with serial measurements of discomfort (using a visual
      analog scale) and transcutaneous tissue O2 tension obtained at zero and 30
      minutes. Measurements of ability to flex, extend, rotate, and laterally bend the
      c-spine were made using a goniometer. The subjects then returned a minimum of
      three days later to complete the opposite half of the study (padded vs unpadded
      boards). RESULTS: Subject discomfort was significantly reduced in the padded
      group compared with the unpadded group (p = 0.024). There was no significant
      difference in flexion (p = 0.410), extension (p = 0.231), rotation (p = 0.891),
      or lateral bending (p = 0.230) for the two groups. There was no significant
      difference in the actual drop in sacral transcutaneous O2 tension from time zero
      to 30 minutes for the padded and the unpadded groups (mean drop = 14.8% +/- 17.5%
      vs 12.2% +/- 16.8%, respectively; p = 0.906). CONCLUSION: Adding closed-cell foam
      padding to a long spine board significantly improves comfort without compromising
      c-spine immobilization. Sacral tissue oxygenation does not appear affected by
      such padding for healthy volunteers.

PMID- 7584749
TI  - Chest compression and ventilation rates during cardiopulmonary resuscitation: the
      effects of audible tone guidance.
AB  - OBJECTIVES: To determine: 1) whether chest compressions during CPR are being
      performed according to American Heart Association (AHA) guidelines during cardiac
      arrest; and 2) the effect of an audio prompt to guide chest compressions on
      compliance with AHA guidelines and hemodynamic parameters associated with
      successful resuscitation. METHODS: An observational clinical report and
      laboratory study was conducted. A research observer responded to a convenience
      sample of cardiac arrests within a 300-bed hospital and counted the rate of chest
      compressions and ventilations during CPR. To evaluate the effect of an audio
      prompt on CPR, health care providers performed chest compression without guidance
      using a porcine cardiac arrest model for 1 minute, followed by a second minute in
      which audio guidance was added. Chest compression rates, arterial and venous
      blood pressures, end-tidal CO2 (ETCO2) levels, and coronary perfusion pressures
      were measured and compared for the two periods. RESULTS: Twelve in-hospital
      cardiac arrests were observed in the clinical part of the study. Only two of 12
      patients had chest compressions performed within AHA guidelines. No patient had
      respirations performed within AHA guidelines. In the laboratory, 41 volunteers
      were tested, with 66% performing chest compressions outside the AHA standards for
      compression rate without audible tone guidance. With guided chest compressions,
      the mean (+/- SD) chest compression rate increased from 74 +/- 22 to 100 +/-
      3/min (p < 0.01). End-tidal CO2 levels increased from 15 +/- 7 to 17 +/- 7 torr
      (p < 0.01). Coronary perfusion pressure increased minimally with audible tone
      guided chest compressions. CONCLUSIONS: The majority of Basic Cardiac Life
      Support--certified health care professionals did not perform CPR according to AHA
      recommended guidelines. The use of audible tones to guide chest compression
      resulted in significantly higher chest compression rates and ETCO2 levels.

PMID- 7584753
TI  - Multicenter study of case finding in elderly emergency department patients.
AB  - OBJECTIVES: To assess the feasibility of a brief comprehensive case-finding
      program for detecting functional, cognitive, and social impairments among elderly
      ED patients and to estimate the prevalence of unknown, undetected, or untreated
      impairments elderly patients may have. METHODS: A multicenter prospective study
      conducted at five private and public hospital EDs in five different communities
      across the country. Patients aged 60 years and older released to their homes
      during 52 randomly selected evening and weekend shifts between February 1 and
      April 30, 1993, were eligible for the case-finding program. They were evaluated
      by medical students who received special training (instructional videotape,
      supervised examinations, and conference calls) in the administration of a
      standardized 17-item protocol that included an interview and simple tests of
      function. The patients' physicians were notified of the screening results and
      were asked to return a one-month follow-up questionnaire. The physicians answered
      whether the presumed problem had been confirmed and whether a treatment plan for
      a new problem had been developed. RESULTS: Patient acceptance of the case-finding
      program was good; 252 of 338 eligible patients (75%) agreed to participate, and
      281 conditions were detected for 242 screened patients (96%). The most frequently
      reported problems were with: performing the activities of daily living (79%);
      vision (55%); lack of influenza vaccination (54%); home environment (49%); mental
      status (46%); general health (41%); falls (40%); and depression (36%). The
      physicians returned questionnaires for 153 patients (63%); 76 patients (50%) were
      evaluated at follow-up visits, during which 47 newly identified problems (62%)
      were confirmed and treatment plans were developed for 25 problems (53%) among 21
      patients. A mean time of 17.7 +/- 10.2 minutes was required to complete the
      screen. CONCLUSIONS: A brief comprehensive case-finding program for functional,
      cognitive, and social impairment among elderly ED patients is feasible. The
      screening uncovered a significant amount of morbidity among older patients
      visiting EDs.

PMID- 7584754
TI  - Stiff-man syndrome: case report.
AB  - Stiff-man syndrome is a rare neurologic disorder characterized by progressive,
      fluctuating muscle rigidity with painful muscle contractions affecting
      predominantly the back and proximal extremities. In the ED, the diagnosis can be
      easily overlooked and misdiagnosed as acute or chronic low back pain and muscle
      spasm. This syndrome is often associated with diabetes, autoimmune diseases, and
      cancer. This report describes an illustrative case of a 39-year-old woman who
      presented to the ED with a two-year history of right leg spasms and low back pain
      that had become so severe in the preceding two days that she was unable to
      ambulate. Clues to the patient's proper diagnosis coincide with the diagnostic
      criteria for stiff-man syndrome: the presence of a slowly progressive stiffness
      of the axial muscles and proximal limb muscles, making ambulation difficult;
      hyperlordosis of the lumbar spine; episodic spasms precipitated by jarring or
      sudden movement; a normal intellectual, sensory, and motor examination when not
      in spasm; and a marked amelioration of symptoms with the IV administration of
      diazepam. High-dose oral diazepam is the maintenance drug of choice.

PMID- 7584756
TI  - Jerry Mandell, leukocyte watcher, searching for the role of cytokines in
      infection.

PMID- 7584755
TI  - The use of a break-even analysis: financial analysis of a fast-track program.
AB  - OBJECTIVE: To calculate the financial break-even point and illustrate how changes
      in third-party reimbursement and eligibility could affect a program's fiscal
      standing. METHODS: Demographic, clinical, and financial data were collected
      retrospectively for 446 patients treated in a fast-track program during June
      1993. The fast-track program is located within the confines of the emergency
      medicine and trauma center at a 1,050-bed tertiary care Midwestern teaching
      hospital and provides urgent treatment to minimally ill patients. A financial
      break-even analysis was performed to determine the point where the program
      generated enough revenue to cover its total variable and fixed costs, both direct
      and indirect. RESULTS: Given the relatively low average collection rate (62%) and
      high percentage of uninsured patients (31%), the analysis showed that the
      program's revenues covered its direct costs but not all of the indirect costs.
      CONCLUSIONS: Examining collection rates or payer class mix without examining both
      costs and revenues may lead to an erroneous conclusion about a program's fiscal
      viability. Sensitivity analysis also shows that relatively small changes in third
      party coverage or eligibility (income) requirements can have a large impact on
      the program's financial solvency and break-even volumes.

PMID- 7584757
TI  - Case conference: complete heart block in a young man.
AB  - A previously healthy 32-year-old man presented to the ED in complete heart block.
      Ischemic, infectious, and inflammatory conditions were considered in the
      differential diagnosis. Management options for complete heart block, the etiology
      of heart block in young adults, and treatment guidelines are reviewed.

PMID- 7584760
TI  - The shocking state of external defibrillation.

PMID- 7584758
TI  - Clinical forensic medicine.

PMID- 7584759
TI  - Adverse effects with administration of phenytoin: infusion pump vs manual
      infusion.

PMID- 7584761
TI  - Speaking sober in the emergency department.

PMID- 7584763
TI  - HIV seroprevalence in emergency department patients: Portland, Oregon, 1988-1991.
AB  - OBJECTIVES: In Portland, OR: 1) to determine the changes in HIV seroprevalence
      for ED patients from 1988 to 1991, 2) to define the characteristics of the HIV
      positive ED patient, 3) to determine the hepatitis B seroprevalence of HIV
      seropositive ED patients, and 4) to demonstrate the feasibility of an ED
      population-based surveillance investigation. METHODS: A prospective, multiyear
      observational, cross-sectional, multicenter, population-based seroprevalence
      study was performed using seven urban hospital EDs. Serologic testing for HIV and
      hepatitis B was performed on excess blood obtained from ED patients. Four
      sampling periods were used at each hospital at 14-month intervals starting June
      1988 and ending December 1991. The blood specimens were obtained concurrently at
      all the participating hospitals. RESULTS: Of 1,681 patients, 17 (1.0%) were HIV
      positive. The HIV seroprevalence rate was relatively stable over time: 0.5%
      (2/444) in 1988, 1.7% (7/396) in 1989, 1% (3/296) in 1990, and 0.9% (5/545) in
      1991. Most (94%) HIV patients were men, 100% were white, 81% were > or = 30 years
      old. Most (59%) of the HIV-positive patients also were positive for hepatitis B
      core antibody. Many (76%) of the HIV-positive patients were known to be positive
      by the emergency health care worker. CONCLUSION: HIV seroprevalence among the ED
      patients in Portland, OR, was generally stable from 1988 to 1991. Many HIV
      positive patients also were hepatitis B-positive, thus representing a double
      occupational infectious disease risk to ED personnel. A significant minority
      (24%) of the HIV-positive patients were not known to be HIV-positive by the ED
      personnel. Universal precautions and hepatitis B immunization are paramount for
      reducing the risk of infectious disease due to exposure to body fluids.

PMID- 7584762
TI  - Screening and empiric treatment for syphilis in an inner-city emergency
      department.
AB  - OBJECTIVE: To examine targeted screening and empiric treatment for syphilis in an
      urban ED. METHODS: Screening of emergency patients during previously arranged
      shifts from July 1991 through January 1992 in a university-affiliated, inner-city
      ED. Emergency patients who perceived that they had high-risk factors for syphilis
      (i.e., cocaine or heroin use or sexual contact with a user of these substances)
      were compared with emergency patients denying high risk. All presumed high-risk
      patients and alternate patients in the group who denied high risk (control group)
      were screened in the ED with the rapid plasma reagin (RPR) test. Empiric
      antibiotic treatment was initiated if the patient was RPR-positive and gave no
      previous history of syphilis. In addition, serum was submitted to the state
      laboratory for VDRL and microhemagglutination-Treponema pallidum (MHA-TP)
      testing. Blinded serologic testing for HIV antibody was performed later on frozen
      serum. RESULTS: Of 806 patients presenting to the ED, 276 (34%) admitted to high
      risk behavior. Of 373 patients tested by RPR in the ED (216 high-risk and 157
      control patients), no significant difference was found between the high-risk and
      the control patients in untreated syphilis [8 (4%) vs 4 (3%)] or positive MHA-TP
      [47 (22%) vs 25 (16%)]. In the high-risk group, the women were more likely than
      the men to be MHA-TP-positive (OR = 2.58, 95% CI 1.12-7.98, p = 0.04). Among the
      women, the MHA-TP was more often positive for the high-risk than for the control
      patients (34% vs 15%, OR = 2.27, 95% CI 1.12-4.67, p = 0.023). For the high-risk
      group, seven (3%) new cases of syphilis were managed empirically, vs three (2%)
      new cases for the control group. HIV antibodies were detected in 16 of 212 (8%)
      high-risk patients and five of 155 (3%) control subjects (p = 0.13). CONCLUSION:
      This inner-city ED population has a high frequency of positive syphilis and HIV
      serologies, regardless of acknowledged drug use risk factors. Therefore, in areas
      reporting high syphilis infection rates, consideration should be given to
      offering screening for syphilis to all emergency patients, along with
      establishment of adequate counseling and follow-up.

PMID- 7584764
TI  - Alcohol use among subcritically injured emergency department patients.
AB  - OBJECTIVES: To determine the incidence of alcohol use in subcritically injured
      patients presenting to the ED, by using a saliva alcohol test (SAT) at ED triage
      during the ED initial assessment; to compare the incidence of alcohol use
      revealed by the SAT with documentation of alcohol use by ED nurses and emergency
      physicians (EPs) blinded to the SAT results; and to describe the demographics of
      the SAT-positive, subcritically injured population. METHODS: A blinded,
      prospective, observational evaluation of ED patients presenting with subcritical
      injuries was performed. The patients were tested for alcohol use with an SAT, and
      a subsequent record review was conducted for extraction of demographic data and
      evidence of documentation of alcohol use by ED nurses and EPs blinded to the SAT
      results. RESULTS: During the study, 791 subcritically injured patients had SATs
      performed. Twenty-one percent of these patients were found to be alcohol-positive
      by SAT. Either the ED nurse or the EP documented a clinical impression of alcohol
      use for 52% of the SAT-positive patients. There were higher SAT-positive rates
      among men (24%), victims of assault (47%), and patients arriving at night (41%).
      CONCLUSIONS: While the SAT identified 21% of the subcritically injured patient
      population as alcohol-positive, ED nurse and EP documentation did not identify
      half of these alcohol-positive patients. Many of these patients may be at risk
      for additional injuries related to their drinking behavior.

PMID- 7584765
TI  - The dextromethorphan defense: dextromethorphan and the opioid screen.
AB  - OBJECTIVE: To determine whether a single oral dose of dextromethorphan produces a
      falsely positive qualitative urine opioid screen. METHODS: A prospective,
      randomized, triple-blind, placebo-controlled, crossover exposure study design was
      used. Twenty adult volunteers participated. All were without routine medications,
      not pregnant or lactating, without known sensitivity to dextromethorphan, and
      negative for urine toxicologic screening immediately prior to testing. These
      volunteers underwent three separate urine Enzyme-Multiplied Immunoassay Technique
      (EMIT) opioid screens. Each screen was performed six hours after the subject had
      ingested a single liquid medication, either dextromethorphan, codeine, or
      placebo. Each volunteer took all three medications randomly, at least 72 hours
      apart. Half of the volunteers took the standard adult dose of dextromethorphan
      (20 mg), while the other half ingested twice this amount (40 mg). The amounts of
      codeine (30 mg) and sucrose placebo (10 mL) remained constant. RESULTS: For these
      young adults (mean age +/- SD = 30.7 +/- 2.8 years), all urine EMIT assays six
      hours after ingestion of dextromethorphan, at both dosage levels, were negative
      for opioids and all other drugs. All assays after codeine and placebo ingestion
      were positive and negative for opioids, respectively. CONCLUSION: Although
      dextromethorphan is structurally similar to opioid drugs, the ingestion of a
      single normal (or even twice normal) dose of dextromethorphan is not likely to
      produce a falsely positive six-hour urine opioid EMIT screen.

PMID- 7584766
TI  - Validation of a rapid urine screening assay for cocaine use among pregnant
      emergency patients.
AB  - OBJECTIVES: To determine the accuracy of the OnTrak rapid urine latex
      agglutination immunoassay (AIA) for testing pregnant ED patients for the cocaine
      metabolite benzoylecgonine (BE), and to determine the frequency of urine BE in
      pregnant ED patients and the association of test results with patient
      demographics. METHODS: A test performance evaluation was conducted using an
      inception cohort of pregnant patients at an urban teaching hospital ED. Patients
      with positive urine chorionic gonadotropin tests who had adequate remaining urine
      samples were studied. Patient demographics, ED diagnoses, and assay results were
      recorded without patient identifiers. Urine was tested using the rapid AIA. The
      first 150 samples were confirmed using a second immunoassay and gas
      chromatography with a nitrogen phosphorus detector. All positive samples also
      were confirmed with thin-layer chromatography, and quantification by gas
      chromatography-mass spectrometry. RESULTS: Twenty of 342 (5.9%, 95% CI 3.4-8.4%)
      pregnant patients had urine samples positive by AIA testing for BE. Confirmation
      testing demonstrated no false-positive or -negative AIA result. Positive test
      results were not associated with specific patient diagnoses or demographics.
      CONCLUSIONS: ED screening for cocaine use among pregnant patients can be
      accurately performed using the OnTrak AIA for BE. In the ED population screened,
      5.9% of the pregnant women had urine samples positive for BE.

PMID- 7584767
TI  - Hematologic safety of intraosseous blood transfusion in a swine model of
      pediatric hemorrhagic hypovolemia.
AB  - OBJECTIVE: To assess the risk of hemolysis, disseminated intravascular
      coagulation (DIC), or fat embolism syndrome (FES) with pressurized intraosseous
      (IO) blood transfusion following hemorrhage. METHODS: A controlled, repeated
      measures, randomized animal study with blinded pathologic evaluations was
      conducted. Sixteen pentobarbital-anesthetized, instrumented immature swine
      underwent a 20-mL/kg hemorrhage into citrate-phosphate-dextrose bags, then
      received autologous blood transfusion via a 16-ga i.v. catheter (eight), or via a
      15-ga IO needle in the proximal tibia (eight) under maximal manual pressure using
      a 30-mL syringe. At baseline and at one hour and 48 hours posttransfusion, blood
      samples were assayed for hemoglobin (Hb), schistocytes, free Hb in plasma,
      bilirubin, lactate dehydrogenase, platelets, fibrinogen, and alveolar-arteriolar
      O2 gradient. Lung sections were examined for inflammation after hematoxylin/eosin
      stain, and for fat emboli after oil red-O-stain. Kidney sections were examined
      for inflammation using hematoxylin/eosin stain. RESULTS: Though the IO
      transfusion rate of 21 +/- 6 mL/min was slower than the i.v. rate of 35 +/- 5
      mL/min (p = 0.0012), all the animals returned to baseline blood pressure within
      15 minutes and survived. The presence of schistocytes and mildly elevated free Hb
      in plasma was noted in both groups at baseline and each time period, and was
      presumed to be due to sampling from the arterial catheter. All other laboratory
      values remained within normal limits and without intergroup differences at any
      time period. No fat embolus was noted, and all lung and kidney specimens were
      free of inflammation. CONCLUSIONS: In this model, pressurized IO blood
      transfusion appears to be hematologically safe, i.e., without risk of appreciable
      hemolysis, DIC, or FES.

PMID- 7584768
TI  - Time to equilibration of oxygen saturation using pulse oximetry.
AB  - OBJECTIVE: To determine the time it takes for O2 saturation measured by pulse
      oximetry to equilibrate after a change is made in supplemental O2 administered by
      nasal cannula in patients with cardiac and pulmonary disease. METHODS: A
      prospective, observational study of a convenience sample of 51 patients treated
      in a university-affiliated ED with nasal cannula O2. Patients were placed on
      and/or subsequently taken off O2 via nasal cannula set at 2 or 4 L/min based on
      clinical indications. Oxygen saturation was measured at 1-minute intervals over a
      30-minute period using finger-probe pulse oximetry. Of the 51 patients in the
      study, 43 were monitored while O2 treatment was initiated and 18 were monitored
      when it was discontinued. RESULTS: Most (95%) of the patients placed on O2
      attained equilibration of O2 saturation within 3.5 minutes. Most (95%) of the
      patients taken off supplemental O2 attained equilibration of O2 saturation within
      4.5 minutes. CONCLUSION: The interval to equilibration of O2 saturation in
      patients receiving O2 by nasal cannula is considerably shorter than the 20-30
      minutes generally suggested. Adequacy of O2 supplementation should be assessable
      much sooner than was previously taught.

PMID- 7584770
TI  - Agreement in the interpretation of extremity radiographs of injured children and
      adolescents.
AB  - OBJECTIVES: To measure agreement beyond chance (kappa) for comparison
      interpretations of extremity radiographs by pediatric radiologists and emergency
      physicians (EPs) and to identify factors associated with disagreement. METHODS: A
      random sample of 205 radiographs was selected from 1,016 patients having x-rays
      of their extremities in the emergency and radiology departments of a tertiary
      care pediatric hospital. Interpretations by the "official" reporting pediatric
      radiologist (ORPR), the treating EP, and a pediatric radiologist blinded to all
      clinical information (BPR) were compared for three categories: "abnormal" (one or
      more of fracture, dislocation, or effusion); "possibly abnormal"; and "normal."
      RESULTS: The overall weighted kappa (Kw) for the ORPRs and the EPs was 0.55. For
      fractures alone, the Kw for the ORPRs vs the EPs was 0.77; and for effusions
      alone, the value was 0.34. The Kw for the ORPRs vs the BPR was 0.63 (range 0.43
      0.83 for individual ORPRs). The main areas of disagreement were in the
      identification of joint effusions and of nondisplaced fractures of the phalanges,
      elbow joint, tarsals, or metatarsals. CONCLUSIONS: There is good agreement
      between EPs and pediatric radiologists in interpreting extremity radiographs of
      injured children and adolescents. Disagreement occurs mainly for effusions or
      minor fractures and for the elbow region. Because of the importance of
      recognizing abnormalities in this region, an educational intervention to improve
      this area of deficiency is recommended.

PMID- 7584769
TI  - Injury as a motivator to reduce drinking.
AB  - OBJECTIVES: To identify predictors of readiness to change drinking behavior by
      minor-injury patients who had positive saliva alcohol tests (SATs) in the ED. To
      develop and test a model intended to be prognostic of readiness to change, which
      included predispositional and injury-event-related variables. METHODS: An on-site
      survey was conducted of minor-injury ED patients sampled consecutively during
      predesignated periods. Patients were identified as SAT-positive during their
      screening evaluations. After giving their consent, they were administered a self
      report battery that assessed predispositional and injury-event-related variables
      as well as readiness to change their drinking. Predictors of readiness to change
      drinking were tested with regression analyses. RESULTS: Twenty-four SAT-positive
      patients participated; there were 18 men and six women (average age 34 years).
      Preinjury predispositional variables were by themselves unrelated to the
      patient's readiness to change while in the ED. Aversiveness of the injury and
      perception of degree of alcohol involvement were injury-event-related variables
      predictive of readiness to change (p < 0.008). Negative consequences attributed
      to drinking prior to the injury event strengthened the association of injury
      aversiveness and alcohol involvement with readiness to change (p < 0.0075).
      CONCLUSION: Interventions to decrease drinking in this population should focus on
      increasing patient awareness of the association between drinking, injuries, and
      other alcohol-related negative consequences.

PMID- 7584772
TI  - Fever and neck pain. Ludwig's angina.

PMID- 7584771
TI  - A new model for teaching corneal foreign body removal.
AB  - OBJECTIVE: To determine whether a skills laboratory for corneal foreign body and
      rust ring removal improves self-assessed skill and confidence. METHODS: A
      prospective trial was conducted as part of the didactic curriculum of a
      university-based residency program in emergency medicine (EM). A convenience
      sample of 26 EM residents and five fourth-year medical students participated. The
      skills laboratory used model corneas made by coating 3.2-cm glass spheres with a
      1-2-mm film of paraffin. Foreign bodies were simulated by embedding small pieces
      of metal into the paraffin. Rust rings were simulated by dipping a hot,
      straightened paper clip into a rust-colored crayon and then into the paraffin.
      The model eyes fit into a life-sized model of a human head. Participants removed
      the foreign bodies and rus rings under supervision, using the slit lamp. Each
      participant anonymously completed a questionnaire before and after participating
      in the skills laboratory. The questionnaire recorded educational level, previous
      experience, and self-assessed comfort and skill levels (0 = lowest, 10 =
      highest). RESULTS: Most (66%) of the participants had not previously removed a
      corneal foreign body; 86% had not previously removed a rust ring. On a ten-point
      scale, the median comfort level for removing a foreign body rose from 2 to 7, and
      the self-assessed skill level rose from 1 to 7 (p = 0.0001). Similar improvements
      in self-assessed comfort and skill levels were seen for rust ring removal.
      CONCLUSIONS: Participation in this skills laboratory significantly improved the
      self-reported comfort and self-assessed skill levels in removing corneal foreign
      bodies and rust rings. This technique provides useful practice of a fine-motor
      procedural skill requiring eye-hand coordination prior to supervised application
      of these skills in clinical practice.

PMID- 7584773
TI  - New models for emergency and ambulatory care at academic health centers--Part I:
      New York city.

PMID- 7584774
TI  - Physician transformation from hero to lover.

PMID- 7584775
TI  - Emergency department photography.

PMID- 7584776
TI  - Pain management in the emergency department.

PMID- 7584777
TI  - Rectal perforation following manual-anal intercourse.

PMID- 7584778
TI  - [Comparative study of the prevalence of hepatitis B virus infection and human
      immunodeficiency virus type 1 infection in the prison population between 1985 and
      1992].
AB  - The prisoner population of the penitentiaries presents an elevated prevalence of
      hepatitis B virus (HBV) and human immunodeficiency type 1 (HIV-1) infection
      markers. In the last few years different measures have been developed to prevent
      infection. This study evaluates whether there have been changes in the prevalence
      of infection by these virus over the last few years within a penitentiary. A
      group of prisoners (n = 163) studied in 1985 were therefore compared with another
      group (n = 750) studied in 1992. Demographic, social, risk and penitentiary
      factors were included. In each of the subjects studied alanine aminotransferase
      (ALT), hepatitis B virus (HBsAG, antiHBs and antiHBc) and anti-HIV-1 markers were
      determined. It was globally observed that following the 7 years between the two
      studies there was a decrease in the prevalence of HBV (X = 14.63, p = 0.0001, OR
      = 2; CI 95%: 1.38-2.9), which was mainly observed in the group of prisoners with
      no drug addiction habits. No differences were observed with regard to the
      prevalence of anti-HIV-1 which remained similar among the IV drug consumers and
      not consumers (64% and 66.6% in 1985 and 1992, respectively). In conclusion, from
      1985 to 1992 a decrease has been observed in the prevalence of hepatitis B virus
      infection in the penitentiary population while the prevalence of anti-HIV-1 has
      remained unchanged.

PMID- 7584779
TI  - [Severe complications of percutaneous hepatic biopsy in patients with orthotopic
      liver transplantation].
AB  - The incidence and type of complications appearing following the performance of
      liver biopsies were analyzed in the first 166 liver transplants in our hospital.
      The presence of a severe complications was defined if a patient presented
      hemoperitoneum, pneumothorax, hemothorax, post biopsy infection or symptomatic
      puncture of abdominal organs other than the liver. Four hundred thirty-eight
      liver biopsies were carried out in 129 patients with a mean of 3.4 biopsies per
      patient. The severe complications were observed in 7 (1.6%), all of which were
      bleeding episodes. Four hemothorax requiring the placement of a thoracic drainage
      tube were observed. In two cases thoracotomy was required with death occurring in
      one patient. Three hemoperitoneum were also seen requiring laparotomy in one and
      transfusion in the remaining two patients. Out of the non transplanted patients,
      four presented severe complications (0.7%), 50% of which were hemoperitoneum. No
      patient presented hemothorax and no deaths were reported. The authors conclude
      that the incidence of severe post liver biopsy complications in transplanted is
      low, similar to that reported in non transplanted patients. Nonetheless, there
      does appear to be a higher incidence of bleeding complications in the
      transplanted patients.

PMID- 7584780
TI  - [Veno-occlusive liver disease due to intake of Senecio vulgaris tea].
AB  - Veno-occlusive liver disease (VOLD) is a cause of portal hypertension by non
      thrombotic obstruction of hepatic venous drainage attributed to multiple
      etiologies (toxic, irradiation, antineoplastic, conditioning for bone marrow
      transplantation). One case of VOLD in a senile patient due to continuous two year
      consumption of Senecio vulgaris tea is reported. This compound, which has a high
      pyrrolizidine alkaloid content induced a subacute course of portal hypertension
      and death. The clinicopathologic features of VOLD and the etiopathogenesis in
      relation to the pyrrolizidine alkaloids present in Senecio vulgaris are
      discussed. The need for considering the history of medicinal plant ingestion in
      patients under portal hypertension studies are strongly recommended as is the
      advice regarding the possible dangers involved in the inappropriate use of
      remedies provided by herbalists.

PMID- 7584781
TI  - [Juvenile polyposis in 2 patients of the same family].
AB  - Two cases of juvenile familiar polyposis (one 40-year-old male and his 14-year
      old daughter) are presented. The girl presented intermittent rectal bleeding
      since the age of 10 with growth retardation and chronic anemia. The child was
      treated by colectomy with more than 100 juvenile polyps without adenomatous
      alterations being observed in the surgical specimen. Juvenile gastric polyps were
      also endoscopically observed. The father underwent sigmoidectomy for a
      adenomatous polyp of this localization. Later review of the surgical specimen
      demonstrated a juvenile polyp with zones of adenomatous alterations. The
      diagnostic difficulties of this rare entity and the therapeutic options available
      are discussed.

PMID- 7584782
TI  - [Arteriovenous malformation of the superior mesenteric artery with secondary
      portal hypertension].
AB  - The case of a 60-year-old patient who was repeatedly admitted for ascitic
      decompensation secondary to hyperflow portal hypertension provoked by congenital
      arteriovenous malformation of the superior mesenteric artery is presented.
      Diagnosis was performed by arteriography. Surgical treatment was conducted with
      total resection of the malformation thereby achieving complete resolution and
      normalization of portal pressure. The literature is reviewed and the
      pathophysiologic mechanism as well as the clinical manifestations, diagnosis and
      treatment are discussed.

PMID- 7584783
TI  - [Gas gangrene as presentation of colonic carcinoma in familial adenomatous
      polyposis].
AB  - One case of gas gangrene by Clostridium septicum associated to colon cancer is
      herein presented. Spontaneous gas gangrene is often associated with neoplasms
      among which hematologic and colon neoplasms are the most frequent. The present
      case has also peculiarity that the colon cancer had developed from a familiar
      adenomatous polyposis syndrome.

PMID- 7584784
TI  - [Hepatopulmonary syndrome and liver transplantation: a realistic alternative?].

PMID- 7584785
TI  - [Alternative treatment to interferon therapy in chronic viral hepatitis].

PMID- 7584786
TI  - [Analysis of information consumption in the Gastroenterologia y Hepatologia
      journal].

PMID- 7584787
TI  - [Cystic tumors of the pancreas: 9 case reports].

PMID- 7584789
TI  - [Hemochromatosis and bacteremia caused by Yersinia enterocolitica].

PMID- 7584788
TI  - [Alcoholic osteopenia: observations].

PMID- 7584790
TI  - [Tuberculous adenitis as a cause of obstructive jaundice].

PMID- 7584791
TI  - Thrombosis as a unitary hypothesis of cardiovascular risk.

PMID- 7584794
TI  - Fibrinogen and cardiovascular risk.
AB  - Ischaemic heart disease and stroke are the major causes of death in the Western
      world. Established risk factors such as smoking, hypertension and
      hypercholesterolaemia explain only some of these events. Most myocardial
      infarctions and cardiac deaths are precipitated by acute occluding coronary
      thrombi, and it has been known for some time that thrombosis participates in
      atherogenesis. For these reasons, haemostatic variables have been included in
      studies of cardiovascular risk. The plasma fibrinogen level is associated with
      both the severity and the extent of coronary, cerebral and peripheral
      atherosclerosis. In prospective studies, fibrinogen was found to be an
      independent predictor of myocardial infarction in both sexes and of stroke in
      men. The plasma fibrinogen level thus provides information on risk over and above
      that supplied by established risk factors. Fibrinogen may play a part in
      atherothrombosis via several mechanisms: (1) by promoting atherosclerosis, (2) as
      an essential component of platelet aggregation, (3) because the amount of fibrin
      deposited and the size of the clot are directly related to the plasma fibrinogen
      level and (4) because fibrinogen increases plasma viscosity. Nevertheless, it is
      not yet possible to determine whether high fibrinogen levels are a cause or a
      consequence of cardiovascular disease because no drugs that selectively lower
      plasma fibrinogen levels are available. In addition, further standardization of
      measurements is needed before routinely including plasma fibrinogen in
      cardiovascular risk scores.

PMID- 7584793
TI  - Presence of thrombosis in coronary atherosclerotic plaques.

PMID- 7584796
TI  - Homocysteine as a risk factor for coronary artery disease.
AB  - This article reviews the evidence that homocysteine is a risk factor for coronary
      artery disease. This evidence ranges from that obtained from in-vitro experiments
      sometimes using non-physiological concentrations of homocysteine to
      epidemiological studies involving large numbers of subjects. Despite the variety
      of studies and methodologies employed, the hypothesis that homocysteine is a risk
      factor remains plausible. The relationship between certain nutrients and serum
      homocysteine and the therapeutic implications of this relationship are discussed.

PMID- 7584792
TI  - Cholesterol and the coronary endothelium.
AB  - The root causes of atherosclerosis lie in cellular events that precede the
      clinical presentation of the disease by many years. The initiating events centre
      around the response of endothelial cells to chronic injury, such as that
      sustained in hypercholesterolaemia. These responses involve the activation,
      attachment and migration of leucocytes and platelets.

PMID- 7584795
TI  - Lipoprotein (a): a prothrombotic risk factor for coronary artery disease.
AB  - New data on the interactions between lipoprotein (a) [Lp(a)] and the coagulation
      fibrinolytic system, which emphasize the importance of the activity of lysine
      binding sites on apolipoprotein (a) [apo(a)], provide an increasingly strong
      basis for the role of Lp(a) in thrombosis. Further insights into the genetic
      control of Lp(a) levels show that inherited factors other than the size of the
      apo(a) gene are important. The clinical relationship between Lp(a) and coronary
      heart disease has been more firmly established by two further large prospective
      cohort studies. The consensus that the concentration of Lp(a) does not predict
      the outcome of thrombolytic therapy still holds, although Lp(a) does affect
      endogenous fibrinolysis after myocardial infarction. The effect of Lp(a) on
      mortality should soon be known.

PMID- 7584797
TI  - Role of catecholamines and sympathetic activation as a risk factor for coronary
      artery disease.
AB  - After acute myocardial infarction and in chronic heart failure, several
      abnormalities of the autonomic control of the heart have been described, and
      evidence of marked neurohumoral activation has been found. Increased sympathetic
      activation can be identified using a number of methods, including simple or
      dynamic measurement of catecholamines and the study of heart rate variability by
      direct sympathetic nerve or muscle activity and by measurement of baroreceptor
      sensitivity. The analysis of heart rate variability is becoming more popular and
      has advantages over other more invasive methods.

PMID- 7584798
TI  - Modification of coronary artery disease using antithrombotic therapy.
AB  - I review some of the literature concerning antithrombotic therapy in coronary
      artery disease. The beneficial effects shown are compatible with the unitary
      hypothesis of thrombosis as a fundamental of cardiovascular risk. The therapeutic
      approach is limited by the haemorrhagic risk produced by most antithrombotic
      therapies. A search should therefore be made for antithrombotic therapies without
      this risk, of which serotonin antagonism appears to be the most promising at
      present.

PMID- 7584799
TI  - Fasting serum insulin levels and coronary heart disease in a Danish cohort: 17
      year follow-up.
AB  - AIM: Our objective was to examine the association between the fasting serum
      insulin level and coronary heart disease (CHD) and cardiovascular disease in 40
      year-old men and women. METHODS: In 1976, all of the men and women born in 1936
      living in four municipalities in the County of Copenhagen were invited for a
      health examination. The participation rate was 87% (504 men and 548 women). All
      of the participants were followed through the Danish register of deaths and the
      register of hospital admissions until 1993. RESULTS: After controlling for
      relevant risk factors (sex, fasting glucose, total cholesterol, high density
      lipoprotein cholesterol, systolic blood pressure, smoking, triglycerides, body
      mass index, physical activity and alcohol consumption) the P value for the
      association between the insulin level and CHD or cardiovascular disease was found
      to be 0.002; the above risk factors did not appear to be intermediate variables
      in a causal chain from insulin level to the development of CHD or cardiovascular
      disease. The significant association between body mass index and CHD disappeared
      when the fasting insulin level was controlled for, and insulin seemed to be an
      intermediate factor between body mass index and CHD. CONCLUSION: The fasting
      serum insulin level in both men and women is a very good predictor of the
      development of CHD and cardiovascular disease even after controlling for relevant
      confounding factors.

PMID- 7584801
TI  - Behavioural characteristics in patients with myocardial infarction: a case
      control study.
AB  - BACKGROUND: Over the past 10-20 years, evidence has accumulated suggesting that
      it is not just biological risk factors that are important for the development of
      coronary heart disease. The present study is one of a series of case-control
      studies in which a wide range of psychosocial factors have been analysed in the
      same population to obtain information on their relationship with myocardial
      infarction, as well as of the interaction between psychosocial and biomedical
      variables. METHODS: The relationship between behavioural factors and non-fatal
      myocardial infarction was studied by comparing consecutively admitted male (n =
      288) and female (n = 55) patients with a population sample of 283 men and 129
      women. All participants were under 65 years of age. The behavioural variables
      (type-A behaviour, health locus of control, sleep problems and alcohol
      consumption) were investigated by means of a self-administered questionnaire.
      RESULTS: No significant differences emerged between patients with myocardial
      infarction and controls in terms of their type-A behaviour pattern. After
      controlling for traditional risk factors (smoking, hypertension, serum
      cholesterol level and diabetes), men with myocardial infarction reported a
      significantly stronger external health locus of control (i.e. a weak belief in
      their capacity to control their health) compared with their controls, as well as
      more problems with sleep and a lower alcohol consumption; women with myocardial
      infarction reported significantly more problems with sleep than their controls.
      CONCLUSION: The importance of health locus of control, sleep problems and alcohol
      consumption is amplified by the fact that they are related to myocardial
      infarction independently of conventional biomedical risk factors. These
      behavioural factors should be studied further in prospective investigations.

PMID- 7584800
TI  - Asymptomatic hyperglycemia in coronary heart disease: frequency and associated
      lipid and lipoprotein levels in the bezafibrate infarction prevention (BIP)
      register. The BIP Study Group.
AB  - BACKGROUND: The lipid profile of patients with type-II diabetes is characterized
      by low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and
      increased levels of lipoprotein (a), all of which may affect the prognosis in
      patients with atherosclerotic cardiovascular disease. This study aimed to assess
      the prevalence of asymptomatic hyperglycemia and the associated lipid profile in
      a large group of patients with documented coronary heart disease. METHODS: From
      February 1990 to October 1992, 14,326 patients aged 45-74 years with documented
      coronary heart disease (a history of myocardial infarction or angina pectoris)
      were screened for inclusion in a secondary prevention study using bezafibrate
      retard. All screened patients underwent a medical examination and a blood test
      after fasting for 14 h. Asymptomatic hyperglycemia was defined as a fasting blood
      glucose level of 140 mg/dl or above in patients with no previous history of
      diabetes mellitus. RESULTS: The prevalence of asymptomatic hyperglycemia was 4%,
      with no differences between the sexes or age groups. Total cholesterol and
      triglyceride levels were significantly higher and the high-density lipoprotein
      cholesterol level significantly lower in asymptomatic hyperglycemic than in
      normoglycemic patients. After multiple adjustments, the relative risk of death
      was 1.75 and 1.71 in patients with diabetes or asymptomatic hyperglycemia
      compared with those with no glycemic disorders. CONCLUSION: Asymptomatic
      hyperglycemia was detected in 4% of patients with ischemic heart disease. The
      lipid profile in these 4% resembles that of patients with confirmed diabetes, and
      their morbidity and mortality may therefore be higher than that of normoglycemic
      patients. Repeated assessment of glucose levels in patients with coronary heart
      disease is mandatory.

PMID- 7584804
TI  - Bibliography of the current world literature.

PMID- 7584803
TI  - Oxidized high-density lipoproteins modulate endothelin secretion by adult bovine
      aortic endothelial cells.
AB  - BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are well
      established as an inverse risk factor for atherosclerosis. This fact is probably
      related to the ability of HDL to induce cholesterol efflux from the vascular
      cell. It is also possible that HDL affects the production of different mediators
      implicated in the development of atheroslerosis. Endothelin is a vasconstricting
      mitogenic peptide involved in the development of atherosclerosis. We studied
      whether native HDL, oxidized HDL and tetranitromethane HDL modulate the
      endothelin secretion of cultured adult bovine aortic endothelial cells. METHODS:
      We determined the effect of native HDL and modified HDLs (oxidized HDL and
      tetranitromethane HDL) on the secretion of endothelin by cultured adult bovine
      aortic endothelial cells. An endothelin radioimmunoassay system was used to
      quantify levels of immunoreactive endothelin in the cultured media. RESULTS:
      Native HDL, tetranitromethane HDL and oxidized HDL produced a highly significant
      stimulation of endothelin secretion (maximum 294% of control), even at low
      concentrations (10 and 20 micrograms/ml). Oxidized HDL2 and oxidized HDL3
      produced a biphasic effect, with maximum secretion occurring with 100
      micrograms/ml oxidized HDL3 (294% of control) and 50 micrograms/ml oxidized HDL2
      (252% of control). The secretion of the peptide decreased with higher
      concentrations of oxidized HDL2 and oxidized HDL3. CONCLUSION: Because modified
      HDLs (oxidized HDL and tetranitromethane HDL) do not bind to the 'HDL receptor'
      to stimulate endothelin secretion, we propose that the stimulation of secretion
      is mediated by unspecific binding of the lipoprotein to the cell membrane.
      Nevertheless, oxidized HDL and tetranitromethane HDL may stimulate endothelin
      secretion via the scavenger-receptor pathway. Our results suggest that HDL and
      modified HDL participate in the regulation of vascular tone.

PMID- 7584805
TI  - General principles of working to develop alaryngeal speech.

PMID- 7584802
TI  - Left ventricular structure and function in previously untreated hypertensive
      patients: the importance of blood pressure, the nocturnal blood pressure dip and
      heart rate.
AB  - BACKGROUND: Cardiac assessment is an important part of risk stratification in
      hypertensive patients. Left ventricular hypertrophy in particular is a powerful
      predictor of subsequent cardiovascular morbidity and mortality. Previous studies
      assessing haemodynamic factors that may be responsible for cardiac changes in
      hypertensive patients have been performed in those previously treated for
      hypertension. To investigate more fully these haemodynamic relationships, a large
      group of previously untreated patients were studied. METHODS: Ninety-eight
      previously untreated hypertensive patients underwent electrocardiography, two
      dimensional and Doppler echocardiography, 24 h ambulatory blood pressure
      monitoring and exercise stress testing. RESULTS: The left ventricular mass index
      (LVMI) was more closely related to mean 24 h than to clinic blood pressures (24 h
      systolic r = 0.48, P < 0.01; 24 h diastolic r = 0.49, P < 0.01; clinic systolic r
      = 0.28, P < 0.01; clinic diastolic r = 0.31, P < 0.01). In addition, the systolic
      nocturnal blood pressure dip was found to be inversely related to LVMI in men (r
      = -0.32, P < 0.01). Of the indices of left ventricular diastolic function, age (r
      = -0.64, P < 0.01), heart rate (r = -0.25, P = 0.02) and LVMI (r = -0.22, P =
      0.02) were independently related to the E-A ratio. Age (r = 0.40, P < 0.01),
      blood pressure (systolic r = 0.39, P < 0.01; diastolic r = 0.43, P < 0.01), the
      nocturnal blood pressure dip (systolic r = -0.38, P < 0.01, diastolic r = -0.31,
      P < 0.01) and LVMI (r = 0.37, P < 0.01) were independently related to the
      isovolumic relaxation time. CONCLUSIONS: Blood pressure was the only independent
      determinant of LVMI; nocturnal blood pressure may be particularly important in
      men. Age and both haemodynamic and structural factors are independent
      determinants of parameters of left ventricular diastolic function in hypertensive
      patients.

PMID- 7584806
TI  - Coping with laryngeal cancer.

PMID- 7584807
TI  - Tracheoesophageal speech.

PMID- 7584808
TI  - The artificial larynx.

PMID- 7584809
TI  - Counseling laryngectomees and families.

PMID- 7584810
TI  - Surgical treatment of laryngeal cancer.

PMID- 7584813
TI  - Standardized performance analysis.
AB  - This article covers the methodology used for calculating reproduction and
      production performance for the Standardized Performance Analysis (SPA) reports.
      Computation, limitations, and interpretations of each measurement are discussed.

PMID- 7584812
TI  - The history of IRM and SPA.
AB  - In Columbus, Ohio, in 1988, five economists prepared an executive summary on
      competitive issues in the beef sector and, specifically, addressed "Can beef
      compete in the 1990s?" One of the challenges to the beef industry is that the cow
      calf sector needed to become more business orientated and create ways of
      maintaining or reducing costs to maintain a competitive position in the food
      production cycle. The IRM concept and the National IRM Coordinating Committee
      have been focusing on helping the cattle industry to achieve that goal.

PMID- 7584811
TI  - Chemotherapy and radiation therapy for laryngeal cancer.

PMID- 7584814
TI  - NCA-IRM desk record.
AB  - Cost of production will remain the primary focus for the cattle industry for
      years to come. Having accurate detailed records to generate this information will
      improve the decision-making process for managers. Certainly, the statement "if
      you do not measure it, you cannot manage it" will be more evident in the future.
      Providing good tools to record the measurements will be important to the
      industry. The IRM will continue to work to fill this need.

PMID- 7584815
TI  - Farm Financial Standards.
AB  - The Farm Financial Standards were developed by a national effort to encourage
      standardization. Standardization includes financial statement formats,
      terminology, and calculations for measuring financial position and format.
      Comparative analysis and education efforts are enhanced greatly by
      standardization. The Standardization Performance Analysis (SPA) system was
      developed on the basis of the performance standards for beef cattle and sheep
      enterprises. This article summarizes the Farm Financial Standards and illustrates
      the calculations with a worksheet.

PMID- 7584816
TI  - Measuring financial performance: an overview of financial statements.
AB  - Financial management has emerged as a critical component in the long-term
      viability of today's ranches and farms. Proper and timely financial reporting and
      analysis of financial statements are valuable tools that agricultural producers
      can use to monitor, coordinate, and plan their operational production and
      marketing schemes and strategies. A side note to preparation of financial
      statements. With the concerns over lender liability issues associated with
      statements either assisted with or prepared by a lending officer, agricultural
      producers will be responsible for preparing their own statements. The lending
      institutions may prepare their own statements in their assessment of the
      financial condition of a business and or individual, but, ultimately, the
      responsibility of financial statements is the borrower's. Some of the material
      presented in this article provides important input for use in such analytical
      programs as the National Cattlemen's Association, Integrated Resource Committees,
      and Standard Performance Analysis (SPA). SPA techniques and associated software
      have been or currently are under development for cow-calf, stocker, seedstock,
      and sheep enterprises. Critical to the analysis is having complete and correct
      financial statements. These analytical programs build on the financial
      statements. These analytical programs build on the financial statements as
      recommended by the FFSTF. Proper financial reporting is critical not only to a
      SPA assessment but also to the overall financial management of today's farms and
      ranches. Recognizing the importance of financial management in production
      agriculture is not enough, taking a proactive stance in one's financial plan is
      paramount to success. Failure to do so will only enhance the exit rates of
      producers from production agriculture.

PMID- 7584818
TI  - Stocker/feeder cattle standardized performance analysis.
AB  - The Standardized Performance Analysis (SPA) for stocker/feed cattle is a
      recommended set of production and financial performance analysis guidelines
      developed specifically for the grazing, growing, and finishing phases of beef
      cattle production. Guidelines were developed by members of the National
      Cattlemen's Association (NCA), Extension Specialists, and the National Integrated
      Resource Management Coordination Committee to provide beef cattle producers with
      a comprehensive, standardized means of measuring, analyzing, and reporting the
      performance and profitability of an operation. This article describes and
      illustrates through an example the performance measures chosen. The NCA certifies
      software and education materials conforming to the Stocker/Feeder Guidelines.

PMID- 7584817
TI  - SPA: marketing and financial performance measures for the cow-calf enterprise.
AB  - The Standardized Performance Analysis (SPA) process can be an important business
      analysis activity. This article outlines the important considerations in terms of
      the process, necessary data, and interpretations and limitations of SPA measures
      of performance. A case ranch example is used to illustrate the SPA process.

PMID- 7584819
TI  - Seedstock beef cattle: SPA.
AB  - The Standardized Performance Analysis (SPA) for seedstock beef cattle (SPA-SB) is
      a recommended set of production and financial performance analysis guidelines
      developed specifically for the seedstock cow-calf, replacement heifer, and the
      sale bull enterprises. These guidelines were developed by members of the National
      Cattlemen's Association (NCA) and the National Integrated Resource Management
      Coordinating Committee to provide beef cattle producers with a comprehensive,
      standardized means of measuring, analyzing, and reporting the performance and
      profitability of an operation. This article describes and illustrates through an
      example the performance measures chosen. NCA certifies software and education
      materials conforming to the Seedstock SPA Guidelines.

PMID- 7584820
TI  - Bibliography of Comparative Biochemistry and Physiology A generated from the
      Current Awareness in Biological Sciences database.

PMID- 7584821
TI  - gamma-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural
      tissues.
AB  - 4-Aminobutyric acid (GABA), a major inhibitory neurotransmitter of mammalian
      central nervous system, is found in a wide range of organisms, from prokaryotes
      to vertebrates. GABA is widely distributed in nonneural tissue including
      peripheral nervous and endocrine systems. GABA acts on GABAA and GABAB receptors.
      GABAA receptors are ligand-gated chloride channels modulated by a variety of
      drugs. GABAB receptors are essentially presynaptic, usually coupled to potassium
      or calcium channels, and they function via a GTP binding protein. In neural and
      nonneural tissues, GABA is metabolized by three enzymes--glutamic acid
      decarboxylase (GAD), which produces GABA from glutamic acid, and the catabolic
      enzymes GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase
      (SSADH). Production of succinic acid by SSADH allows entry of the GABA carbon
      skeleton into the tricarboxylic acid cycle. Alternate sources of GABA include
      putrescine, spermine, spermidine and ornithine, which produce GABA via
      deamination and decarboxylation reactions, while L-glutamine is an additional
      source of glutamic acid via deamination. GAD from mammalian brain occurs in two
      molecular forms, GAD65 and GAD67 (referring to subunit relative molecular weight
      (Mr) in kilodaltons). These different forms of GAD are the product of different
      genes, differing in nucleotide sequence, immunoreactivity and subcellular
      localization. The presence and characteristics of GAD have been investigated in a
      wide variety of nonneural tissues including liver, kidney, pancreas, testis, ova,
      oviduct, adrenal, sympathetic ganglia, gastrointestinal tract and circulating
      erythrocytes. In some tissues, one form (GAD65 or GAD67) predominates. GABA-T has
      been located in most of the same tissues, primarily through histochemical and/or
      immunochemical methods; GABA-T is also present in a variety of circulating cells,
      including platelets and lymphocytes. SSADH, the final enzyme GABA catabolism, has
      been detected in some of the tissues in which GAD and GABA-T have been
      identified, although the presence of this enzyme has not been in mammalian
      pancreas, ova, oviduct, testis or sympathetic ganglia.

PMID- 7584823
TI  - Riboflavin binding proteins and flavin assimilation in insects.
AB  - Recent studies on developmentally regulated hemolymph proteins in insects have
      shown that two proteins, a lipoprotein and a member of a hexamerin gene family,
      bind riboflavin. The biosynthesis, developmental regulation, and properties of
      these proteins are described and compared with the riboflavin-binding proteins
      and flavin distributions in vertebrates. The importance of riboflavin-binding
      proteins in insect development is discussed in relation to existing information
      and avenues for future research are presented.

PMID- 7584822
TI  - The influence of isotonic exercise on cardiac hypertrophy in arterial
      hypertension: impact on cardiac function and on the capacity for aerobic work.
AB  - Intense physical training through isotonic exercises has controversial effects in
      individuals with moderate to severe hypertension. In this study, normotensive
      Wistar rats and rats with renovascular hypertension (Goldblatt II) were subjected
      to intense physical exercise involving two 50-min swimming sessions per day for a
      period of 12 weeks. At the end of the study, we evaluated the effect of training
      on arterial pressure, the capacity for aerobic work and cardiac function. Our
      results demonstrate that intense physical training has no effect on the arterial
      blood pressure of normotensive rats or of animals with moderate renovascular
      hypertension. Hypertensive animals with cardiac hypertrophy require a greater
      period of training in order to attain the same capacity for aerobic work as
      normotensive rats. This difference may result from an inability of the former
      animals to increase cardiac compliance, thereby impeding more extensive usage of
      the Frank-Starling mechanism to subsequently increase the systolic cardiac
      performance. Cardiac hypertrophy induced by exercise did not summate with that
      induced by arterial hypertension. Physical exercise normalized the end-diastolic
      left ventricular pressure in hypertensive animals without any corresponding
      increase in the compliance of the chamber. The first derivative of left
      ventricular pulse pressure (+/- dP/dt) was greater in the hypertensive trained
      group than in the hypertensive sedentary rats. These observations suggest that a
      systolic dysfunction of the left ventricle involving an elevated residual volume
      secondary to arterial hypertension may be corrected by physical exercise such as
      swimming.

PMID- 7584824
TI  - Characterization of microvillar membrane proteins of dog small intestine by two
      dimensional electrophoresis.
AB  - A method for analysing microgram amounts of microvillar membranes by two
      dimensional electrophoresis (protein mapping) is described, and has been used to
      characterize the microvillar proteins of the small intestine of German shepherd,
      corgi, and beagle dogs. Detergent-solubilized microvillar membranes were
      radiolabelled with 14C and separated by isoelectric focussing followed by SDS
      PAGE. Proteins were detected fluorographically and glycoproteins by lectin
      affinity staining. The microvillar hydrolases alkaline phosphatase and dipeptidyl
      aminopeptidase IV were identified by active-site labelling and aminopeptidase N
      by immunoprecipitation. Changes following pancreatic duct diversion were
      consistent with accumulation of pro-sucrase-isomaltase and diminished expression
      of the sucrase and isomaltase subunits. Cytoskeletal proteins were concentrated
      in the core fraction remaining after extraction of microvillar membranes with
      Triton X-100. There were no consistent differences between dogs of different
      breed, and the canine protein maps were similar to the human.

PMID- 7584825
TI  - A diversity of enzymes involved in the regulation of reversible tyrosine
      phosphorylation in sea urchin eggs and embryos.
AB  - Reversible tyrosine phosphorylation is involved in the fertilization reaction and
      early embryogenesis of the sea urchin (Foltz and Shilling, 1993; Ramachandran et
      al., 1993). To determine the enzymes present that may be involved in this
      regulation, we used a PCR screen to identify sequences that encode protein
      tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP). We identified
      five PTKs and eight PTPs using cDNA libraries from two sea urchin species at two
      different stages of development, and the similarities to known PTK and PTP amino
      acid sequences ranged from 70 to 95%. The cognate proteins represented both
      "receptor"-class and cytoplasmic enzymes. Using RNAse protection assays we found
      that the respective mRNAs showed many accumulation profiles that we have grouped
      into three basic patterns: (1) mRNA levels that do not vary by more than two to
      three times throughout development; (2) mRNA levels highest in eggs or ovaries;
      and (3) mRNA levels highest in gastrula or pluteus stages. mRNAs specific to
      adult somatic cells of the ovary were not found, nor were mRNAs that accumulated
      selectively at the blastula stage. The results show that a diversity of enzymes
      involved in the regulation of reversible tyrosine phosphorylation is present in
      eggs and embryos of the sea urchin and that the differential accumulation in
      development of each mRNA suggests specific functional responsibilities by members
      of these enzyme families.

PMID- 7584827
TI  - Free sphingosines in oral epithelium.
AB  - Free sphinogosines, intermediates in the biosynthesis of ceramides and inhibitors
      of protein kinase C, have been found to be present in significant concentrations
      in epidermis and oral epithelia of the pig (Sus scrofa). Concentrations of
      sphingosines were higher in the outer portion of epidermis (4.4 mg/g), palatal
      epithelium (3.9 mg/g) and buccal epithelium (0.7 mg/g) compared to the inner
      portion of the epithelia (1.0, 0.9 and 0.4 mg/g, respectively). Free sphingosines
      may provide antimicrobial activity at the epithelial surfaces, and the
      sphingosine gradient may modulate epithelial differentiation.

PMID- 7584826
TI  - Immunohistochemical localization of phospholipase A2 in human and bovine male
      reproductive organs.
AB  - Phospholipase A2 (PLA2) taken from human seminal plasma and purified about 1450
      fold was injected into rabbits to prepare polyclonal antibodies. The antiserum
      produced and the IgG purified from the antiserum were used to compare the
      immunohistochemical localization of PLA2 in the human male reproductive system
      with that in the bull. In Western blot analyses, the polyclonal antibodies cross
      reacted with purified PLA2s from human seminal plasma, bovine Cowper's glands and
      with partly purified PLA2 from bovine seminal vesicle fluid. On the other hand,
      purified PLA2s from Crotalus adamanteus venom, bovine pancreas or from bovine
      prostate were not recognized by the polyclonal antibodies. With an indirect
      peroxidase technique, PLA2 was localized in the epithelial cells of the human
      prostate and bovine seminal vesicles as well as in the fibrous connective tissue
      of bovine Cowper's gland. Indirect peroxidase staining also gave an
      immunoreaction in the enlarged acrosomes of round spermatids in the human testis.
      Using an indirect immunofluorescence method, ejaculated human spermatozoa
      revealed an immunoreaction which was not uniform, and the reaction was restricted
      to the middle piece and the acrosomal and postacrosomal regions. In conclusion,
      human seminal plasma, spermatozoa and prostate PLA2s were immunohistochemically
      related to those from bovine Cowper's gland, seminal vesicles and seminal fluid.

PMID- 7584828
TI  - The hemocyanin of the Californian black sea hare, Aplysia vaccaria Winkler.
AB  - The hemocyanin of the Californian black sea hare. Aplysia vaccaria exists in
      solution largely as a di-decameric protein with a molecular weight of close to
      8.0 x 10(6) and a sedimentation coefficient of about 92 S. Light-scattering
      measurements at pH 8.0, 0.1 M Tris, 0.05 M Mg2+, 0.01 M Ca2+ gave a molecular
      weight of 8.0 +/- 0.6 x 10(6), and scanning transmission electron microscopic
      determinations (STEM) gave a slightly higher particle mass of 8.49 +/- 0.41 x
      10(6) daltons. Measurements using the STEM method gave a particle mass of 4.27 +/
      0.26 x 10(6) daltons for the dissociated half-molecules or decamers. Light
      scattering measurements on the dissociated monomers at pH 11.1 and in 8.0 M urea
      gave molecular weights of 4.74 x 10(5). Sedimentation measurements in the
      presence of 0.01 M Mg2+ indicate that the hemocyanin of A. vaccaria is largely in
      the di-decameric form in the pH region from about 5.0 to 8.0. Above pH 8.0 the
      hemocyanin di-decamers are found to dissociate to half-molecules or decamers,
      followed by dissociation to dimers and monomers as the pH is increased above pH
      9.0.

PMID- 7584829
TI  - Wallaby transthyretin.
AB  - A cDNA library was constructed from liver RNA of the Australian diprotodont
      marsupial Macropus eugenii, the Tammar wallaby. A cloned full-length
      transthyretin cDNA was sequenced. The derived amino-acid sequence showed 68%
      overall similarity to that of human transthyretin, with 86% similarity in the
      thyroxine binding site. Comparisons of nucleotide and amino acid sequences from
      several vertebrate species indicated that the greatest differences were in the
      region corresponding to the disordered N-terminus of mature human transthyretin.
      The evolutionary trees deduced from parsimony analyses of amino acid and
      nucleotide sequences of transthyretins, are consistent with that derived from
      fossil records.

PMID- 7584830
TI  - Increased expression and activity of ornithine decarboxylase in chicks
      genetically selected for rapid growth rate.
AB  - Polyamines are essential requirements for cell proliferation and their role in
      stimulation of RNA, DNA, and protein synthesis is clearly established. Ornithine
      decarboxylase is a key enzyme in the biosynthesis of the polyamines and its
      activity is regulated in response to factors that stimulate cell proliferation.
      Steady-state ODC mRNA levels and enzyme activity were measured in muscle of
      chicks genetically selected for increased growth rate or for egg production. In
      muscle, muscle satellite cells and myotubes, two ODC mRNA transcripts are present
      of molecular size 2.05 and 1.75 kb. Northern blotting analysis suggest that these
      transcripts are produced as a result of using different polyadenylation sites.
      Between day 1 and day 6 after hatching, a period of rapid muscle growth in these
      animals, a peak in muscle ODC mRNA levels is followed by a peak in enzyme
      activity in both lines. Significantly higher ODC mRNA levels and enzyme activity
      are associated with selection for rapid growth in the broiler line. The results
      are consistent with other data showing that ODC is a major factor in cell growth
      and provide further evidence that it is a candidate 'trait-gene' for growth.

PMID- 7584832
TI  - Distribution and characterization of apolipoproteins in Chrysemys picta plasma.
AB  - Very low density lipoproteins (VLDL) (d < 1.006), low density lipoproteins (LDL)
      (1.006 < d < 1.063), and high density lipoproteins (HDL) (1.063 < d < 1.21) were
      isolated by ultracentrifugation from the plasma of female and male Chrysemys
      picta. The protein components of lipoproteins (apolipoproteins) were analysed by
      electrophoresis in denaturing polyacrylamide gradient gel. Gel filtration
      chromatography, electroelution from gradient gel and two dimensional
      electrophoresis were utilized to partially purify and characterized the main
      apolipoproteins. A 350 kDa Apo B-like protein was found associated with VLDL and
      LDL fractions. In HDL, Apo AI was the main protein component which, after
      purification on Sephadex G-200, showed the same electrophoretic mobility as human
      Apo AI (28 kDa). When analysed by two dimensional electrophoresis, Apo AI gave a
      pI value of 5.2. A 36 kDa apolipoprotein was purified from VLDL fraction. The
      purified putative Apo E showed an electrophoretic mobility slightly lower than
      human Apo E (34 kDa). The only sex difference observed was a band in the female
      bottom fraction (d > 1.21) with similar electrophoretic mobility to vitellogenin.

PMID- 7584833
TI  - Cloning and expression of frog rhodopsin cDNA.
AB  - The cDNA encoding the putative rhodopsin of frog (Rana catesbeiana) was cloned
      and expressed in cultured cells. The deduced amino acid sequence (354 residues)
      has more than 90% identity with the rhodopsins of two other frogs (Rana pipiens
      and Xenopus laevis) and 80% identity with other vertebrate rhodopsins. The
      isoelectric point calculated from the sequence was about 8.2, which is
      intermediate between rhodopsins and the cone visual pigments of higher
      vertebrates. The cloned cDNA was expressed in cultured mammalian cells. The
      difference absorbance maximum before and after photobleaching was about 500 nm,
      the same as that observed in the retina, demonstrating that the cloned cDNA does
      indeed encode functional rhodopsin.

PMID- 7584831
TI  - An ouabain-sensitive Na+,K(+)-ATPase in tentacles of the sea anemone
      Stichodactyla helianthus.
AB  - Tentacles of Stichodactyla helianthus contain an ouabain-inhibitable, (Na+,K+)
      stimulated ATPase. The K0.5 for Na+ was 24 mM and for K+, 3.2 mM. The apparent
      affinity for ouabain was low, I50 = 10(-4) M. The order of cation affinities was
      Rb+ > K+ > NH4+ = Cs+. The catalytic subunit of the enzyme comprised a single
      band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, M(r) = 105
      kDa, that was phosphorylated by [32P]ATP in the presence of NaCl and
      dephosphorylated by the addition of KCl. The alpha subunit was weakly reactive
      with antibodies directed against the rat alpha subunit.

PMID- 7584836
TI  - Sea urchins--a new model for PAF research in embryology.
AB  - This study reports on the effect of PAF on sperm motility, fertilization and
      early embryo development in the sea urchin Strongylocentrotus intermedius. PAF
      proved to be the amplifier of sperm motility and fertilizing capability at 10(-8)
      10(-9) M and was toxic at higher concentrations. BN 52201 did not counteract the
      PAF action. The advantages of using sea urchins for PAF research in embryology
      are discussed.

PMID- 7584835
TI  - Expression profile of Ldh-a in the developing rat (Rattus norvegicus) testis
      suggests regulation at the translational level.
AB  - Expression of Ldh-a and Ldh-c mRNAs was examined in the rat testis. The mRNA
      levels of both Ldh-a and Ldh-c increase during testicular maturation. In the
      adult testis, Ldh-a mRNA is expressed maximally in primary spermatocytes.
      Comparison of the Ldh-a mRNA expression profile with its translation product
      suggests that this gene is translationally down-regulated during spermatogenesis.

PMID- 7584837
TI  - Amino acid composition of pinniped milk.
AB  - The total amino acid concentration and the amino acid pattern, i.e. the relative
      proportion of each amino acid (protein-bound plus free) to the total amino acids,
      in the milks of the Northern elephant seal, Antarctic fur seal, California sea
      lion, and Australian sea lion were determined. Total amino acid concentration was
      10% (w/v) or greater and did not vary significantly among species. The most
      abundant amino acids in the milks of all species were glutamate, proline and
      leucine. Essential amino acids were 40%, branched-chain amino acids were 20%, and
      sulfur amino acids were 4% of the total milk amino acids in all species. There
      were differences among the pinnipeds in some of the individual amino acids; the
      milk of the Northern elephant seal was the most distinct among the pinnipeds with
      higher histidine, serine and cystine contents and a lower methionine content than
      that of other pinnipeds. There was little effect of stage of lactation on total
      amino acid concentration or amino acid pattern in pinniped milk. Comparison of
      milk from the four pinniped species with that of 14 other mammalian species
      suggests commonality in milk amino acid pattern despite the wide variation in
      total amino acid concentration among the species.

PMID- 7584834
TI  - Adenosine triphosphate catabolism in bovine spermatozoa.
AB  - Adenosine triphosphate metabolism in caudal epididymis bovine spermatozoa was
      studied. Measurements by HPLC at appropriate time intervals of the spermatozoa
      content of ATP and its derivatives were carried out under different experimental
      conditions. In the presence of 2-D-glucose, cellular ATP was transformed almost
      quantitatively into ADP and AMP at a rate of 2.3 nmol/min per 10(8) cells. At the
      same time, ADP and AMP accumulated at a rate of 1.52 and 0.58 nmol/min per 10(8)
      cells, respectively. In the first 4 min, about 50% of total ATP was degraded, the
      AEC of the cells dropped to non-physiological values while the content of other
      nucleosides did not vary significantly. Inorganic P(i) content also remained
      unchanged. Under non-induced conditions up to 240 min, no variations of the
      adenylic content and of the EC value was observed. Under induced and non-induced
      conditions, IMP and adenosine were not detected within the spermatozoa. The lack
      of IMP might be ascribed either to the absence of AMP deaminase, whose activity
      has never been found in the spermatozoa or to the intracellular environment which
      down regulates the activity of the enzyme. In order to explain low levels and
      absence of variations of adenosine, several enzymic investigations were carried
      out. Adenosine kinase activity was not determined, therefore the transformation
      of adenosine into AMP had to be excluded. Nevertheless, enzymic activities
      potentially able to dephosphorylate the formed AMP are present in the
      spermatozoa. Our findings are indicative of the existence in the spermatozoa of
      acid and alkaline phosphatase and of 5'-nucleotidase membrane-derived.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584838
TI  - Partial purification of plasma phenoloxidase of the yellow fever mosquito Aedes
      aegypti L. (Diptera: Culicidae).
AB  - A nitrocellulose-based assay was developed using a dot-blot apparatus to detect
      phenoloxidase activity in column fractions. Using this assay, plasma
      phenoloxidase was partially purified from Aedes aegypti larvae using hydrophobic
      interaction chromatography, gel filtration, and ion-exchange chromatography. The
      molecular weight (M(r)) native enzyme was 130,000, and it contained subunits of
      76,000, 62,000, and 58,000. Two phenoloxidase peaks were observed by ion exchange
      chromatography, and these fractions had distinct polypeptide profiles as detected
      by SDS-PAGE.

PMID- 7584839
TI  - Overexpression of genes in health and sickness. A bird's eye view.
AB  - Many human disorders are associated with gene alterations, such as
      translocations, deletions, insertions, inversions, rearrangements and point
      mutations. However, an overexpression of certain normal genes could also
      contribute to the pathology of neurological disorders, retinal degeneration,
      diabetes, fibrosis of lung, cardiac and skin, programmed cell death and cancer.
      This implies that the regulated expression of normal genes is an important factor
      in determining human health. An understanding of the mechanisms involved in the
      control of expression of normal genes may provide a greater or more refined
      success in correcting, delaying or possibly preventing the disorders by a gene
      therapeutic approach.

PMID- 7584840
TI  - Two endogenous methyl-alpha-D-glucopyranoside uptake activities in Xenopus
      oocytes.
AB  - Endogenous methyl-alpha-D-glucopyranoside (AMG) uptake in Xenopus oocytes was
      measured with 14C-labeled AMG. Two AMG uptake activities, one Na(+)-dependent and
      the other Na(+)-independent, were observed in oocytes incubated with 2 mM AMG.
      However, only Na(+)-dependent uptake was observed at 0.1 mM AMG. Na(+)-dependent
      AMG uptake was attributed to the endogenous Na+/glucose co-transporter since it
      was inhibited by phlorizin. On the other hand, Na(+)-independent AMG uptake was
      inhibited by cytochalasin B or 2-deoxy-D-glucose. This suggests that AMG can be
      transported by the endogenous facilitated glucose transporter as well as by the
      endogenous co-transporter. In addition, a substrate range of the endogenous co
      transporter was examined by competition experiments.

PMID- 7584841
TI  - In vitro Catabolism of very low density lipoproteins from horse (Equus caballus)
      by the action of autologous lipoprotein lipase.
AB  - Incubation of equine very low density lipoproteins with lipoprotein lipase
      isolated from horse postheparin plasma resulted in the formation of lipoproteins
      of a higher density. Lipoproteins isolated after incubation and plasma
      lipoproteins had a different chemical composition and triacylglycerol fatty acid
      pattern. In vitro-obtained low density lipoproteins contained substantially more
      phospholipids and triacylglycerols but significantly less cholesteryl esters than
      native low density lipoproteins. Comparing the triacylglycerol fatty acid pattern
      of plasma very low density lipoproteins and in vitro--obtained low density
      lipoproteins, a drastic decrease in the proportion of linolenic acid was observed
      with increasing density.

PMID- 7584843
TI  - Storage proteins in ants (Hymenoptera:Formicidae).
AB  - Storage proteins are a major feature of holometabolous development in insects,
      accumulating during the larval period and disappearing during metamorphosis. In
      ants (Hymenoptera:Formicidae), storage proteins also play important roles in
      adult females. Three types of storage proteins have been characterized from ants:
      hexamerins, proteins high in glutamine/glutamic acid, and very high density
      lipoproteins (VHDLs). The hexamerins have moderately high levels of aromatic
      amino acids and belong to the arthropod hemocyanin family of proteins. The
      proteins high in glutamine/glutamic acid can form hexamers under some conditions,
      but the subunit size is larger than that of typical hexamerins. The VHDLs are
      dimeric and share features with storage chromoproteins described from
      Lepidoptera. In Camponotus festinatus (Formicinae), storage proteins are found in
      adult ants in two situations. First, lack of brood stimulates workers to
      accumulate the same two storage hexamers found in larvae. Second, young virgin
      queens store large reserves of these proteins before mating. Protein storage by
      queens has been confirmed in two other subfamilies of ants, indicating it is
      widespread. The capacity to store proteins as adults enables queens to rear brood
      without leaving the nest and workers to store rich reserves and regulate larval
      diet seasonally.

PMID- 7584845
TI  - Electrophoretic polymorphism in rabbit tear lysozyme.
AB  - Rabbit tears were found to contain two lysozymes which differed in their
      electrophoretic mobility and were designated tear lysozymes 1 and 2. Rabbit tear
      lysozyme 1 was purified to homogeneity by conventional purification methods. It
      was found to be distinct from other known mammalian c-type lysozymes, rabbit tear
      lysozyme 2 and the major rabbit gastrointestinal lysozyme. The activity profile
      is centered around the neutral region with an optimum of 7 which is slightly
      lower than that for chicken lysozyme. The thermal stability as well as inhibition
      profiles by the substrate analogues, N-acetylglucosamine (NAG) and chitotetraose
      (NAG)4 are comparable to those of chicken lysozyme. Based on its molecular weight
      and catalytic properties this isozyme is classified as a c-type lysozyme.

PMID- 7584844
TI  - Interaction of arginase with metal ions: studies of the enzyme from human liver
      and comparison with other arginases.
AB  - As determined by atomic absorption, fully activated human liver arginase
      contained 1.1 +/- 0.1 Mn2+/subunit. Upon dissociation to inactive subunits (<
      0.01 Mn2+/subunit), there was decreased intensity and a red shift in the
      tryptophan fluorescence emission spectra of the enzyme, and the resulting species
      were markedly sensitive to thermal and proteolytic inactivation by trypsin.
      Arginine and lysine specifically protected the subunits from heat inactivation.
      Subunit activation by Mn2+ followed hyperbolic kinetics (Kd = 0.08 +/- 0.01
      microM). In addition to Mn2+, Ni2+ and Co2+ converted inactive subunits into
      active monomers, and favoured their association to the oligomeric state of the
      enzyme (M(r) = 120,000 +/- 2000). The replacement of Mn2+ by Ni2+ or Co2+
      resulted in significant changes in Vmax without any change in the Km values for
      the substrates (arginine or canavanine) or the Ki value for lysine inhibition.
      The results support our previous suggestion (Carvajal et al., 1994) that Mn2+ is
      not essential for substrate binding to arginase, and substantiates the conclusion
      that species differences may exist in the interaction of arginase with metal
      ions.

PMID- 7584842
TI  - Purification properties and specificity of cathepsin D from Cyprinus carpio.
AB  - Cathepsin D was purified 750-fold from a homogenate of Cyprinus carpio muscles.
      The purified enzyme has a molecular weight of 36,000, is inhibited by pepstatin
      and is active between pH 2.7 and 3.7 when tested on hemoglobin as the substrate.
      It consists of two isoenzymes with pIs of 5.65 and 6.1, respectively. The mode of
      cleavage of the beta chain of oxidized insulin was determined by analysis of the
      N-terminal amino acids of the cleaved peptides. The major points of cleavage of
      the beta chain of oxidized insulin are 56% at Tyr16-Leu17 and 40% at Phe25-Tyr26.
      The minor points of cleavage are at Leu15-Tyr16, Phe24-Phe25, Gly23-Phe24, Leu11
      Val12, Ala14-Leu15 and Gln4-His5.

PMID- 7584846
TI  - Developmental patterns of diurnal variations in 3-hydroxy-3-methylglutaryl
      coenzyme A reductase, D-site binding protein (DBP), and serine dehydratase mRNA
      levels in rat liver.
AB  - Rats were housed under a 12-hr light (07:00-19:00)/12-hr dark cycle. Hepatic 3
      hydroxy-3-methylglutaryl coenzyme A reductase mRNA appeared at 3 weeks of age,
      and diurnal variation was established at 5 weeks of age. Diurnal variation of the
      D-Site binding protein (DBP) mRNA was faintly seen 1 week after birth and became
      evident with age. Serine dehydratase mRNA level was high at 11:00 in the livers
      of rats at 2-3 days of age, and at 15:00 in those at 1-2 weeks of age. The rhythm
      became ambiguous at 3-4 weeks of age, but an adult-type rhythm with a peak at
      19:00 was established at 5 weeks of age.

PMID- 7584848
TI  - Comparative study on brush border membranes prepared from rat and monkey small
      intestine by Ca2+ and Mg2+ precipitation.
AB  - Brush border membranes, prepared by Ca2+ or Mg2+ precipitation, from monkey or
      rat small intestine were compared for marker enzyme enrichment and lipid
      composition. Membranes prepared from rat intestine by Mg2+ precipitation were
      less pure in terms of their marker enzyme enrichment than Ca2+ precipitated
      membranes. Moreover, Mg2+ precipitated membranes were contaminated by basolateral
      membranes as evidenced by the enrichment of Na(+)-K+ ATPase. The content and
      composition of phospholipids were different in Mg2+ and Ca2+ precipitated
      membranes. The membranes prepared by the two methods from monkeys were identical
      in their marker enzyme enrichment and lipid composition and unlike those obtained
      from the rat, there was no basolateral membrane contamination.

PMID- 7584847
TI  - Activities of carbohydrate and amino acid metabolizing enzymes from liver of mink
      (Mustela vison) and preliminary observations on steady state kinetics of the
      enzymes.
AB  - The activity and some kinetic parameters of the key enzymes of the glycolysis,
      the gluconeogenesis and the amino acid catabolism from the liver of male and
      female mink have been determined and compared to the corresponding activities
      from rat and cat. The activities of glucose-6-phosphatase and pyruvate kinase are
      dependent on sex, both being higher in females. Except for pyruvate carboxylase
      the glycolytic and the gluconeogenic enzyme activities of the mink are higher
      than those of rat and cat; especially the activities of phosphoenolpyruvate
      carboxykinase and glucose-6-phosphatase are markedly higher. The activities of
      glutamate dehydrogenase and glutamate oxaloacetate transaminase are smaller than
      the corresponding activities of rat but higher than those of cat. The results
      suggest that mink has a high capacity for gluconeogenesis compared to rat.

PMID- 7584849
TI  - Fatty acids in the triglycerides and phospholipids of the common shrew (Sorex
      araneus) and the water shrew (Neomys fodiens).
AB  - Fatty acid composition of the liver, brown fat, thigh muscle and heart of Sorex
      araneus and Neomys fodiens was determined by GLC and GLC-MS. In both species of
      shrew the total amounts of omega 3-PUFAs in the phospholipids were greater than
      those in the triglycerides. Sorex araneus, which feeds solely on a terrestrial
      diet, had a larger total amount of omega 6-PUFAs in the triglycerides of the
      brown fat. The phospholipids of the thigh muscle and heart of Neomys fodiens,
      however, contained more omega 6-PUFAs than did those of Sorex araneus. These
      results suggest that the fatty acid composition of the membrane phospholipids of
      shrews is largely genetically regulated and is affected by diet less than the
      composition of triglycerides. The main C16-monounsaturated fatty acid of most of
      the specimens studied was 16:1 omega 5, which is unusual among mammals.

PMID- 7584850
TI  - Proteolysis of Japanese quail and chicken plasma apolipoprotein B and
      vitellogenin by cathepsin D: similarity of the resulting protein fragments with
      egg yolk polypeptides.
AB  - Plasma very-low density lipoprotein (VLDL) and vitellogenin (VTG) from mature
      female Japanese quail (Coturnix coturnix japonica) and chickens (Gallus
      domesticus) were isolated and digested in vitro with cathepsin D (EC3.4.23.5).
      The incubation mixtures were then reduced and subjected to gradient (4.5-18%) SDS
      polyacrylamide gel electrophoresis. Protein fragments were stained with either
      Coomassie Brilliant Blue R-250 (VLDL digests) or Coomassie Brilliant Blue R-250
      containing 20 mM AlCl3 (VTG digests). Fragments resulting from the in vitro
      enzymatic digestion of quail and chicken plasma VLDL-apolipoprotein B (apo B) and
      VTG closely resembled those produced in vivo and isolated from egg yolks of each
      respective species. Phosvitin, a proteolytically derived fragment of VTG,
      primarily existed as a single band (M(r) approximately 42 kDa) in Japanese quail
      yolk granules. In contrast, chicken phosvitin mainly consisted of a cluster of
      phosphoproteins ranging in size from approximately 37 to 45 kDa. In addition to
      reporting a novel species difference in phosvitin moieties, the present study is
      the first to examine the role of cathepsin D in the generation of egg yolk
      proteins from plasma precursors in Japanese quail. Confirmatory evidence also was
      provided concerning the important role of this aspartic endopeptidase in the
      proteolytic cleavage of plasma VLDL-apo B and VTG in the chicken.

PMID- 7584852
TI  - Induction of ovalbumin mRNA by ascorbic acid in primary cultures of tubular gland
      cells of the chicken oviduct.
AB  - The present study was conducted to investigate the effects of aging and medium
      supplements on steroid-induced ovalbumin mRNA in primary cultures of tubular
      gland cells from the chicken oviduct. In experiment 1, the effect of aging was
      examined by comparing the responsiveness to administration of estrogen and
      corticosterone in cells derived from laying hens and estrogen-primed chicks. In
      experiment 2, the effect of supplementing a culture medium with various compounds
      on the responsiveness to the steroid treatment was examined. In experiment 3, the
      effect of supplementing with ascorbic acid was tested in the presence or absence
      of the steroid hormones. The results indicated that the oviduct cells from
      immature chicks had clearer induction of ovalbumin mRNA by the steroid treatment
      than did those from laying hens. Among medium supplements, ascorbate increased
      the steroid responsiveness to a great extent, and fetal calf serum had modest,
      but long lasting, induction of ovalbumin mRNA. The drastic induction of ovalbumin
      mRNA by ascorbic acid supplementation was exerted only when the steroid hormones
      were present in the medium, implying that the effect of ascorbic acid may be
      auxiliary in steroid-induced transcription of the ovalbumin gene.

PMID- 7584851
TI  - Bovine chondrocyte link protein cDNA sequence: interspecies conservation of
      primary structure and mRNA untranslated regions.
AB  - The sequence for bovine link protein cDNA, including 108 bases of the 5'
      untranslated region (UTR) and 768 nucleotides of the 3' UTR, was determined from
      polymerase chain reaction products and bovine articular chondrocyte cDNA clones.
      The deduced primary structure for bovine link protein predicts a protein 354
      amino acid residues in length. Comparative analysis with link protein sequence
      from several other species revealed overall high conservation of protein coding
      sequence. High nucleotide sequence conservation was observed within the extensive
      5' and 3' UTRs of bovine, human, pig, chick and rat link protein mRNA. As
      evidence that the UTRs might play a role in regulation of link protein mRNA
      turnover, multiple occurrences of the adenosine-uridine binding factor motif
      A(Ua)A were found to be conserved between species within 3' UTRs. A
      polyadenylation signal was conserved between the bovine and chicken sequence, use
      of which would result in the smallest of multiple bovine link protein mRNA
      species observed by Northern blot analysis.

PMID- 7584853
TI  - Serum amyloid A protein in humans and four animal species: a comparison by two
      dimensional electrophoresis.
AB  - Two-dimensional electrophoresis and N-terminal analysis were used to study serum
      amyloid A protein (SAA) from humans, mink, fox, goat and rabbit. Previously
      uncharacterized SAA variants were demonstrated in fox, goat and rabbit, and
      considerable interspecies homology was seen. In rabbit, two novel SAAs were
      characterized, and SAA1 and SAA2 were demonstrated in mink and rabbit sera. The
      results confirm previous cDNA studies and indicate that SAA do possess an
      important function also in fox and goat.

PMID- 7584855
TI  - N-acetyltransferase activity in the quail (Coturnix coturnix jap) duodenum.
AB  - The activity and kinetics of N-acetyltransferase (NAT) in the quail duodenum were
      studied by radioenzymatic assay. NAT activity was highest when incubated under 37
      degrees C, at pH 5.8 for 15 sec. Of the four substrates tested (tryptamine, 5,6
      dihydroxytryptamine, serotonin, and N-acetylserotonin at concentrations of 0.08-4
      mM), only tryptamine showed the substrate saturation phenomenon when incubated
      with the duodenal enzyme and acetyl-14C-coenzyme A. The saturation concentration
      of tryptamine was about 4 mM. Using the double reciprocal plot and regression
      equation, the Michaelis constant (Km) and maximal rate (Vmax) of NAT activity
      were found to be 0.204 mM and 0.917 nmol.mg protein-1.min-1, respectively.
      Diurnal study demonstrated higher NAT activity at middark (3.7 nmol.mg protein
      1.min-1) and lower activity at midlight (2.4 nmol.mg protein-1.min-1), suggesting
      a circadian rhythm of the enzyme activities in the quail duodenum.

PMID- 7584854
TI  - Immunosuppressive activity of angiogenin in comparison with bovine seminal
      ribonuclease and pancreatic ribonuclease.
AB  - Angiogenin, a member of the pancreatic-like ribonuclease family with a special
      biological action (RISBAses), is a basic protein that induces blood vessel
      formation. Another member of these special ribonucleases, bovine seminal
      ribonuclease (BS RNase), displays biological properties, including
      aspermatogenic, embryotoxic, antitumor and immunosuppressive activities. The
      effects of two angiogenin preparations tested on the biological activities
      mentioned above are reported and compared with those of BS RNase and RNase A. In
      contrast to RNase A, which was ineffective in all biological activities tested,
      angiogenin suppressed significantly the proliferation of human lymphocytes
      stimulated by phytohemagglutinin or concanavalin A or by allogenic human
      lymphocytes (mixed lymphocyte culture). However, angiogenin did not affect the
      growth of human tumor cell lines, development of cow and mouse embryos and
      spermatogenicity in mice. On the basis of these results, angiogenin is the first
      monomeric ribonuclease described so far that displays immunosuppressive activity
      similar to that of the dimeric BS RNase. The immunosuppressive activity of
      angiogenin might synergize with the effect on neovascularization of tumor tissues
      and thus contribute to the development of tumor.

PMID- 7584856
TI  - Isolation and properties of white skeletal muscle alpha-actinin from sea-trout
      (Salmo trutta) and bass (Dicentrarchus labrax).
AB  - Fish alpha-actinin purified from sea-trout and bass white muscle by means of two
      different extraction procedures was used to investigate the eventual presence of
      different muscle isoforms in Z-disks. These fish alpha-actinins have the same
      apparent molecular weight (100 kDa) and the same isoelectric point (pI = 5.6),
      and also have a total antigenic identity towards anti-bass and anti-chicken alpha
      actinin antibodies, suggesting a single molecular species. The role of fish alpha
      actinin as an anchorage site for thin actin filaments and elastic titin filaments
      in Z-bands was studied. Despite conservation of the actin-binding site, fish
      alpha-actinin has a better actin-binding ability (kD = 0.3 microM) than chicken
      smooth muscle alpha-actinin (kD = 1.6 microM). Several other structural and
      functional characteristics of fish alpha-actinin were also studied: conservation
      of sequence and domain structure, the role of divalent ions (Ca2+, Mg2+) and the
      dielectric constant of the medium in alpha-actinin-actin interaction. Although
      the reason for fish white muscle alpha-actinin's close affinity to actin was not
      clearly established, our results suggested that the physicochemical environment
      of the Z-filaments in Z-disks might be crucial.

PMID- 7584858
TI  - 2,3-Bisphosphoglycerate-independent phosphoglycerate mutase is conserved among
      different phylogenic kingdoms.
AB  - We have previously demonstrated that maize (Zea mays) 2,3-bisphosphoglycerate
      independent phosphoglycerate mutase (PGAM-i) is not related to 2,3
      bisphosphoglycerate-dependent phosphoglycerate mutase. With the aid of specific
      anti-maize PGAM-i antibodies, we demonstrate here the presence of a closely
      related PGAM-i in other plants. We also describe the isolation and sequencing of
      a cDNA-encoding almond (Prunus amygdalus) PGAM-i that further demonstrates this
      relationship among plant PGAM-i. A search of the major databases for related
      sequences allowed us to identify some novel PGAM-i from different sources: plants
      (Arabidopsis thaliana, Oryza sativa and Antithamniom sp.), monera (Escherichia
      coli, Bacillus subtilis and Bacillus megaterium) and animals (Caenorhabditis
      elegans). All of these amino acid sequences share a high degree of homology with
      plant PGAM-i. These observations suggest that the PGAM-i from several biological
      kingdoms constitute a family of protein different from other proteins with
      related enzymatic function and arose from a common ancestral gene that has
      diverged throughout its evolution.

PMID- 7584857
TI  - Decreased phospholipid polyunsaturated fatty acid content and superoxide
      dismutase activity in cardiac muscle of malignant hyperthermia-susceptible swine.
AB  - Homogenates of cardiac left ventricle from malignant hyperthermia-susceptible
      (MHS) pigs produced a circa 72% more pentane than those from malignant
      hyperthermia-resistant (MHR) animals, indicating enhanced peroxidation of n-6
      fatty acids. This is consistent with the observed circa 70% decrease in total
      phospholipid polyunsaturated fatty acids (PUFA) in MHS compared with MHR tissue,
      a decrease mainly due to the quantitatively greater loss of n-6 PUFA. Although
      the percentage loss of n-3 PUFA was greater than that of n-6 PUFA (90% vs 60%),
      absolute amounts were insufficient to register as ethane production. Three-fold
      greater phospholipid content of MHS compared with MHR ventricles indicates
      reduced neutral lipid content probably due to increased catecholamine
      stimulation. These findings were associated with a small but significant decrease
      in superoxide dismutase activity in MHS tissues.

PMID- 7584860
TI  - Allozyme divergence among four representatives of the subfamily Alcelaphinae
      (family: Bovidae).
AB  - We used protein gel electrophoresis to study genetic diversity within and between
      blue wildebeest (Connochaetes taurinus), black wildebeest (C. gnou), red
      hartebeest (Alcelaphus buselaphus caama) and blesbok (Damaliscus dorcas
      phillipsi). Twenty-nine protein encoding loci were resolved, average
      heterozygosity ranged from 3.25-5.36% and between population gene diversity
      accounted for the major share of the total relative gene diversity (69.34%).
      Genetic distance values ranged from 0.021 to 0.132 and 0.029 to 0.136, with
      closest identity between the two wildebeest species (as expected for congeneric
      species). The results are discussed with specific reference to taxonomic
      relationships between species within the subfamily where interbreeding is known
      to have occurred.

PMID- 7584859
TI  - Echinococcus granulosus, E. multilocularis and mammalian liver-type alkaline
      phosphatases: a comparative study.
AB  - The alkaline phosphatases (EC 3.1.3.1) from Echinococcus granulosus and E.
      multilocularis (Cestoda) were compared to each other and to a liver-type enzyme.
      The purified proteins (210 and 220 kDa, respectively) had a tetrameric structure
      composed of 4, 56/53 kDa subunits. Enzymatic removal of their N-linked sugar
      moieties abolished the differences in their apparent molecular weight under
      reducing conditions. After phase separation in Triton X-114, the E.
      multilocularis enzyme was the most amphiphilic, and treatment with PI-P1C reduced
      the amount of the parasite alkaline phosphatases that were in a hydrophobic form
      by about 50%. Both parasite enzymes were highly resistant to heat denaturation
      and insensitive to the inhibitors L-phenylalanine and L-leucine. In addition, L
      homoarginine, levamisole and ZnCl2 can be used to differentiate the parasite and
      mammalian liver-type enzymes from each other. The Echinococcus alkaline
      phosphatases have original biochemical properties when compared to the mammalian
      liver-type enzyme.

PMID- 7584861
TI  - Lipid provisioning of turtle eggs and hatchlings: total lipid, phospholipid,
      triacylglycerol and triacylglycerol fatty acids.
AB  - Lipid composition of eggs and hatchlings was studied in painted, snapping and
      Blanding's turtles from western Nebraska. The average total lipid proportions of
      the egg yolk, post-embryonic yolk and hatchling soma dry masses were high in
      painted turtles (29.80%, 42.16% and 14.18%, respectively) relative to snapping
      and Blanding's turtles (egg yolk < 14%, postembryonic yolk < 17%, hatchling soma
      < 2%). The proportion of total egg yolk lipid used during development varied
      among species (painted turtles, x = 45.4%; snapping turtles, x = 68.9%;
      Blanding's turtles, x = 86.6%). Total lipid data are consistent with patterns
      reported for turtle species whose hatchlings overwinter in the nest (e.g.,
      painted turtles) vs those whose hatchlings emerge in the fall (e.g., snapping and
      Blanding's turtles). In all species, the total lipid quantity of egg and
      hatchling components was primarily triacylglycerol (> 63%), an energy storage
      form. Predominant triacylglycerol fatty acids in eggs and hatchlings were 16:0,
      16:1 and 18:1, and concentration changes of some yolk fatty acids occurred during
      development. The average phospholipid (a membrane form) quantity of the egg and
      hatchling components was relatively low in painted turtles (< 2% of the total
      lipid). In snapping and Blanding's turtles, the relatively large phospholipid
      proportion of the post-embryonic yolks (approximately 7%) could potentially
      contribute more to post-embryonic growth in these species than the phospholipids
      of painted turtle post-embryonic yolks.

PMID- 7584862
TI  - Age-associated changes in the content and fatty acid composition of brain
      glycerophospholipids.
AB  - The fatty acid composition of total lipids and individual phospholipids and the
      ratio of cholesterol-to-phospholipid content were studied in cerebral cortex,
      subcortical white matter, cerebellum and medulla oblongata/pons in 4-, 21.5- and
      28-month-old rats. The cholesterol-to-phospholipid molar ratio in subcortical
      white matter, medulla oblongata/pons and cerebellum in 28-month-old rats was
      found to be 17, 17 and 16% higher, respectively, than in adult rats. These
      alterations in the molar ratio were produced as a result of a net increase in
      cholesterol content rather than by changes in the total phospholipid content. The
      content of alkenylacylglycerophosphoethanolamine (alkenylacyl GPE) increased in
      28-month-old rats with respect to 4-month-old rats, following the order cerebral
      cortex > cerebellum > medulla oblongata/pons > subcortical white matter. The
      fatty acid composition of total lipids showed an increase in monounsaturated
      fatty acids (MUFA) and a decrease in polyunsaturated fatty acid (PUFA) content
      with increasing age in all regions studied, such changes being more marked in
      cerebellum, medulla oblongata/pons and subcortical white matter than in cerebral
      cortex. The proportion of 22:6(n-3) in cholineglycerophospholipids in the
      different brain regions of 28-month-old rats showed a slight decrease with
      respect to that in adult rats following the order cerebellum > medulla
      oblongata/pons > subcortical white matter, whereas that of 20:4(n-6) decreased
      only in cerebellum. Ethanolamineglycerophospholipid fatty acid composition was
      modified in 28-month-old rats through a marked increase in monounsaturated fatty
      acids (18:1(n-9) and 20:1(n-9) specifically) in all brain areas. The MUFA content
      of alkenylacyl GPE increased with increasing age in all the regions studied, in
      the order cerebral cortex > medulla oblongata/pons > subcortical white matter >
      cerebellum. An increase in the MUFA content of diacylglycerophosphoethanolamine
      was observed in medulla oblongata/pons and cerebellum of aged rats with respect
      to control rats. PUFA content of alkenylacyl GPE decreased mainly in medulla
      oblongata/pons, cerebral cortex and subcortical white matter of aged rats. The
      PUFA content of serineglycerophospholipids was the most affected by aging.
      Changes occurred mainly in the content of 22:6(n-3), 22:4(n-6) and 20:4(n-6) in
      cerebellum and of 22:6(n-3) and 22:4(n-6) in subcortical white matter. Changes in
      the inositolglycerophospholipid fatty acid content of 28-month-old rats were
      observed mainly in medulla oblongata/pons, which showed a decrease in PUFA
      (22:4(n-6) and 22:6(n-3)) content and an increase in MUFA (18:1 and 20:1).

PMID- 7584863
TI  - Conservation of functionally important epitopes on myelin associated glycoprotein
      (MAG).
AB  - Phylogenetic conservation of protein domains often points to functionally
      important regions. As a step toward mapping these sites on myelin associated
      glycoprotein (MAG) we have determined the species distribution of epitopes
      recognized by a panel of anti-MAG antibodies (Ab). Monoclonal antibodies (mAb)
      B11F7, GenS3 and 28 recognized MAG only in mammalian species. However, the mAb
      513 which inhibits MAG binding recognized a conformational epitope in a wider
      distribution of species including, human (Homo sapiens), bovine (Bos taurus), rat
      (Rattus norvegicus), chicken (Gallus gallus), quail (Coturnix coturnix japonica),
      lizard (Iguana iguana), snake (Thamnophis sirtalis), frog (Xenopus laevis) and
      turtle (all tetrapods) but not in goldfish (Crassius aurata) (a teleost).
      However, only MAG from mammals was shown to bind rat dorsal ganglion neurons
      (DRGs) suggesting that structures additional to those recognized by mAb 513 must
      be involved in function. Antibody 28, on the other hand, recognized only MAG
      species which bound to neurons, suggesting that this epitope, in comparison with
      mAb 513, more closely represented the functionally important region of MAG.
      Observed species differences in glycosylation of MAG may be functionally
      significant. A newly developed polyclonal Ab against MAG recognized the protein
      in tetrapods and teleosts, but not chondricthyes. The results show that MAG is
      present in a wide spectrum of species.

PMID- 7584864
TI  - Hormonal regulatory adjustments during voluntary diving in Weddell seals.
AB  - Subadult male Weddell seals were instrumented with microcomputer-based backpacks
      and were then monitored during voluntary diving and recovery periods in McMurdo
      Sound, Antarctica. Depth and duration of diving, swim speed, and dive pattern
      were routinely monitored. An indwelling venous catheter was used to collect
      plasma samples at various time periods before and following diving episodes, so
      that changes in plasma concentrations of hormones and of metabolites could be
      measured. Adrenergic and nitroxidergic regulatory effects were assessed
      indirectly by measuring concentration changes in catecholamine and cyclic
      guanosine monophosphate (cGMP), respectively. The studies found that (i), except
      for dives of less than several minutes, epinephrine and norepinephrine both
      increased as a function of diving duration, then rapidly decreased during
      recovery (with a half time of about 10 min), (ii) that the changes in
      catecholamine concentrations correlated with splenic contraction and an increase
      in circulating red blood cell mass (hematocrit), (iii) that the changes in
      catecholamines, especially [epinephrine], were inversely related to
      insulin/glucagon ratios, which mediated a postdiving hyperglycemia, and (iv) that
      in long dives (but not short ones) the changes in catecholamines correlated with
      increasing reliance on anaerobic metabolism, indicated by increased plasma
      lactate concentrations. These diving-catecholamine relationships during voluntary
      diving at sea were similar to those observed during enforced submergence
      (simulated diving) under controlled laboratory conditions. At the end of diving,
      even while catecholamine concentrations were still high, many of the above
      effects were rapidly reversed and the reversal appeared to correlate with
      accelerated nitric oxide production, indirectly indicated by increased plasma
      cGMP concentrations. Taken together, the data led to the hypothesis of important
      adrenergic regulation of the diving response in seals, with rapid reversal at the
      end of diving and during recovery being regulated by nitroxidergic mechanisms.

PMID- 7584866
TI  - Chymotrypsin isoenzymes in Atlantic cod; differences in kinetics and substrate
      specificity.
AB  - Two chymotrypsin isoenzymes, ChT1 and ChT2 from cod pyloric caeca showed
      different kinetics against both chromogenic peptide and proteinaceous substrates.
      The enzymes have similar kcat values but ChT1 had substantially lower values for
      KM compared to ChT2. The enzymes also differed in cleaving site specificity with
      the oxidised B-chain of bovine insulin as substrate. ChT1 exhibited broader
      cleavage specificity compared to ChT2. This difference is parallel to the
      difference between chymotrypsin C and the A and B isotypes in higher animals.
      Direct N-terminal amino acid sequence analysis of the isoenzymes revealed that
      the active forms consisted of two polypeptide chains. The A chains were 13
      residues long and ChT1 and ChT2 differed in three positions. The Cod enzyme A
      chains differed from the A-chains of bovine chymotrypsin in four and five
      positions, respectively. The N-terminal part of the B-chains of the cod enzymes
      were nearly identical to that of the bovine A and B isoenzymes.

PMID- 7584865
TI  - Isolation of cDNA encoding a novel serpin of crayfish hemocytes.
AB  - We have cloned a serpin-type proteinase inhibitor from a crayfish hemocyte cDNA
      library. The deduced amino acid sequence consists of 429 amino acids with a
      putative signal peptide of 21 amino acids. The mature protein has a calculated
      molecular mass of 45,029 daltons. Identities ranging up to 38% were observed
      between the crayfish serpin and other members of the serpin family. Phylogenetic
      analysis shows that the crayfish serpin has a closer relationship to insect
      serpins than to other animal serpins. Phe369-Ser370 were proposed to be the P1
      P1' residues of the inhibitor reactive site. This protein was found to be
      expressed in hemocytes but not in the hepatopancreas of the crayfish Pacifastacus
      leniusculus.

PMID- 7584867
TI  - Age-related changes of mRNA expression of amyloid precursor protein in the brain
      of senescence-accelerated mouse.
AB  - APP695 mRNA is only expressed in the brains of SAM. The expression of APP mRNA in
      SAM P1 mice brains is more marked than that in SAM R1 mice brain. APP mRNA
      expression was increased with advancing age in all brain regions of SAM P1 mice
      compared with SAM R1. Especially, the changes of the amount of APP mRNA in the
      prosencephalon and the mesencephalon are significant at P value of 0.05. We
      suggest that overexpression of APP mRNA may be related to accelerated aging
      phenomenon in the SAM brain. This is the first report of age-related increase in
      the amount of APP mRNA in the SAM brain.

PMID- 7584868
TI  - Urinary biochemical markers for bone resorption during the menstrual cycle.
AB  - In order to analyze the effects of serum ovarian steroid hormones on bone
      metabolism during the menstrual cycle, we have measured urinary levels of type I
      collagen cross-linked N-telopeptide (NTx), hydroxylysylpyridinoline (HP),
      lysylpyridinoline (LP). and hydroxyproline (OH-Pr) in nine healthy Japanese
      women, aged 22-43 years, with normal ovarian function. The cycles were
      synchronized by serum LH peaks, and follicular and luteal periods were normalized
      by lengths. Serum gonadotropins and ovarian sex steroids showed significantly
      different cyclic variations during the menstrual periods. Urinary NTx remained
      unchanged during the early follicular period, showed a rise during the mid- and
      late follicular period, and a fall during the mid- and late luteal periods. There
      were significant differences in NTx levels between early follicular period and
      midfollicular period (P < 0.01), or late follicular period (P < 0.05), and
      between early luteal period and late luteal period (P < 0.05). The levels of HP
      and LP showed a rise during the early an midfollicular periods and a fall during
      the midluteal period. The correlation of NTx with urinary OH-Pr was better than
      with urinary HP or LP (r = 0.731 versus r = 0.449 or r = 0.634). This variation
      suggests that cyclic changes in serum ovarian sex steroids might modulate bone
      resorption markers during the menstrual cycle.

PMID- 7584869
TI  - Evolution of spinal bone loss and biochemical markers of bone remodeling after
      menopause in normal women.
AB  - The main objective of this study was to describe longitudinal patterns of spinal
      bone loss in normal women who undergo a natural menopause. The second objective
      was to determine if a proportion of women suffer excessively rapid postmenopausal
      bone loss from the spine. If this was the case it was the aim to devise a means
      of predicting the woman at excess risk; but if all women lost bone at similar
      rates, the aim was to document changing loss rates over the first 5-8
      postmenopausal years. Responding women in six suburban general practices recalled
      for cervical smears who had their last menstrual period 9- 36 months previously
      were invited to participate in a longitudinal study of bone loss and the
      biochemical markers plasma osteocalcin and urinary hydroxyproline. Sixty-four
      subjects agreed to participate, a response rate of 80%. In the ensuing 5 years,
      six received hormone replacement therapy and are not reported on. The main
      outcome measures were rates of spinal bone loss over 5 years, measured by dual
      photon absorptiometry, and radial bone loss over the first 2 years measured to
      quantitative computed tomography. Spinal bone loss was similar between
      individuals, with 94% of the variability in the data being accounted for by a
      statistical model that assumed parallel rates of bone loss. A less restrictive
      model allowing women to have different rates of spinal bone loss accounted for
      12% more of the remaining variance in the data than the previous model. However,
      rates of radial bone loss were more dissimilar between women than rates of spinal
      loss. The results of the biochemical data collected serially showed that the
      plasma osteocalcin rose slowly to a plateau at 5 years postmenopause; in
      contrast, the hydroxyproline fell progressively with time over the whole period
      of study. These results were interpreted as being consistent with diminishing
      rates of bone destruction which gradually reequilibrated with bone formation as
      time passed after menopause.

PMID- 7584871
TI  - Users of low-dose glucocorticoids have increased bone loss rates: a longitudinal
      study.
AB  - Although high doses of glucocorticoids are believed to cause bone loss, the
      effects of low glucocorticoid doses are still controversial. Our study examined
      the effects of low-dose glucocorticoids on the rate of bone loss at three
      appendicular bone sites. The study population was a cohort of elderly Japanese
      Americans, 1094 women and 1378 men. The women were all postmenopausal. At the
      baseline examination the mean age of the women was 64 years (range 45-81), and
      the mean age of the men was 68 years (range 61-82). Glucocorticoid users (19
      women and 21 men) had used oral systemic or inhaled glucocorticoids on a regular
      schedule for more than 1 month (mean use was 2.1 years for the women and 1.9
      years for the men). The most common dose was equivalent to 5 mg/day of
      prednisone; fewer than 15% of users had taken doses equivalent to 10 mg/day or
      more. Changes in bone mass at the calcaneus, distal radius, and proximal radius
      were documented using bone densitometry at 1 to 2-year intervals over an 8-year
      period. The initial bone mass of the glucocorticoid users and controls was
      similar at the baseline examination. The subsequent loss rates among females
      during glucocorticoid use, however, were approximately double that of the
      controls. Among males, bone loss rates during glucocorticoid use were 2-3 times
      that of controls for the calcaneus and radius sites. The differences between
      glucocorticoid users and controls persisted after adjusting for confounding
      variables such as age and use of thiazides and estrogens.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7584870
TI  - Vertebral fractures and osteopenia in chronic alcoholic patients.
AB  - To assess whether vertebral fractures are associated with osteopenia in chronic
      alcoholic patients, a transversal study was carried out in 76 chronic alcoholic
      males and 62 age-matched healthy males. Lumbar bone mineral density (BMD) by dual
      photon absorptiometry and spinal chest X-ray films were done in all patients.
      Twenty-seven patients (36%) had vertebral fractures, but only 5 of them had a BMD
      below the fracture threshold. Twenty-two patients (29%) had osteoporosis by
      densitometric criteria. There were no significant differences in lumbar BMD
      between alcoholic patients with and without vertebral fractures (1.11 +/- 0.2
      versus 1.13 +/- 0.2, P = ns). Previous trauma was recorded in 24 of the 27
      patients with vertebral fractures and in 28 of the 49 patients without vertebral
      fractures (P < 0.001). Moreover, patients with vertebral fractures had more
      peripheral fractures than patients without vertebral fractures (81% versus 49%, P
      = 0.01). Only one patient was aware of a previous episode of traumatic vertebral
      fracture. In conclusion, chronic alcoholics frequently have traumas and vertebral
      fractures, the latter despite having a lumbar BMD above the fracture threshold,
      suggesting a frequent but unrecognized association between both processes. These
      results suggest that both spine films and BMD measurements should be obtained for
      diagnosis of osteoporosis in alcoholic patients.

PMID- 7584872
TI  - Differential effects of glucocorticoids on human osteoblastic cell metabolism in
      vitro.
AB  - Clinical observations suggest that the onset and severity of glucocorticoid (GC)
      induced osteoporosis is dependent on the duration of the GC treatment and the
      applied GC compound. To test whether these in vivo observations are reflected by
      different in vitro effects of various synthetic GCs on human bone cell metabolism
      we isolated human osteoblast-like cells (HOC) from bone biopsies of healthy (no
      clinical symptoms of arthritis or arthrosis) adults who underwent selective
      orthopedic surgery. HOC were identified as bone cells by 1,25-vitamin D3
      stimulated increase of specific alkaline phosphatase (ALP) activity, secretion of
      osteocalcin and type-I procollagen peptide, and the ability to form mineral in
      vitro. We investigated the effects of dexamethasone (dexa), methylprednisolone
      (mpred), prednisolone (pred), and deflazacort (defla) on DNA-synthesis, ALP, and
      osteocalcin (OC)- and type-I procollagen peptide secretion of HOC in vitro. In
      summary, (1) GC exposure stimulates DNA synthesis after 6-12 hour treatment
      periods; (2) dex and mpred strongly inhibit DNA (48-hour treatment) and collagen
      synthesis but stimulate ALP, whereas pred and defla exhibit smaller effects on
      DNA synthesis, ALP, and collagen production; and (3) all tested glucocorticoids
      inhibit OC secretion by HOC in vitro. Thus, the effect of GC on DNA synthesis of
      HOC varies with the duration of GC exposure, and dex and mpred more potently
      affect HOC metabolism in vitro than pred and defla.

PMID- 7584874
TI  - Enamel matrix protein turnover during amelogenesis: basic biochemical properties
      of short-lived sulfated enamel proteins.
AB  - The formation and turnover of sulfated enamel proteins was investigated by SDS
      PAGE, fluorography, and TCA-precipitations using freeze-dried incisors of rats
      injected intravenously with 35S-sulfate (35SO4) and processed at various
      intervals from 1.6 minutes to 4 hours thereafter. Some rats were injected first
      with 35SO4 followed 5 minutes later by 0.3 mg of cycloheximide. This was done to
      terminate protein translation and allow events related to extracellular
      processing and degradation of the sulfated enamel proteins to be visualized more
      distinctly. Other rats were injected with cycloheximide followed at 0 minutes
      (simultaneous injection) to 30 minutes later by 35SO4. This was done to
      characterize the time required for proteins to travel from endoplasmic reticulum
      to Golgi apparatus, where they became sulfated. The results indicated that enamel
      organ cells (ameloblasts) rapidly incorporated 35SO4 into a major approximately
      65 kDa protein that was secreted into the enamel within 6-7.5 minutes. This
      parent protein appeared to be processed extracellularly within 15 minutes into
      major approximately 49 kDa and approximately 25 kDa fragments which themselves
      had apparent half-lives of about 1 and 2 hours, respectively. There were also
      many minor sulfated fragments varying in molecular weight (Mr) from approximately
      13-42 kDa, which appeared to originate from extracellular processing and/or
      degradation of the parent approximately 65 kDa sulfated enamel protein or its
      major approximately 49 kDa and approximately 25 kDa fragments. Experiments with
      glycosidases further suggested that the majority of sulfate groups were attached
      to sugars N-linked by asparagine to the core of the approximately 65 kDa sulfated
      enamel protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584876
TI  - Changes in serum carboxyterminal telopeptide of type I collagen in an
      experimental model of canine osteomyelitis.
AB  - Blood biochemical indices of bone turnover were followed up for 1 month in six
      dogs with experimental osteomyelitis. The bone infection resulted in significant
      increase in parameters of bone formation (serum bone alkaline phosphatase and
      serum osteocalcin) and bone resorption [serum carboxyterminal telopeptide of type
      I collagen (i-ICTP)] as early as the end of the second week after the operation
      and inoculation. There was strong evidence that serum i-ICTP levels could be
      useful for the early diagnosis of postoperative complications in veterinary
      orthopedics, such as posttraumatic osteomyelitis.

PMID- 7584877
TI  - Bone-bonding behavior of three heat-treated silica gels implanted in mature
      rabbit bone.
AB  - Silica gel has been reported to induce apatite nucleation on its surface in vitro
      and it can act as a stimulant that induces formation of chemical apatite (Ca-P)
      layers on the surfaces of bioactive glass-ceramics. In this study, apatite
      formation in response to and the bone-bonding behavior of silica gels implanted
      in the tibiae of mature rabbits were studied. Implants were made from three
      silica gels treated at 400, 800, and 1000 degrees C, and the effects of such heat
      treatment on the above parameters were investigated. The silica gel was made by
      hydrolysis and polycondensation of tetraethoxysilane in aqueous solution
      containing polyethylene glycol. Rectangular implants (15 mm x 10 mm x 2 mm) of
      each heat-treated silica gel were implanted into both tibial bones of mature male
      rabbits, which were killed 4 or 8 weeks after implantation, and the tibiae
      containing the implants were dissected out. The bone-implant interfaces were
      investigated using Giemsa surface staining, contact microradiography, scanning
      electron microscopy-electron probe microanalysis, and X-ray diffraction.
      Histologically, no bonding of bone to any of the silica gels was observed at any
      time postimplantation. Soft tissue was observed at the bone-silica gel interface,
      but there were no giant foreign body or inflammatory cells. A Ca-P-rich layer was
      observed only on small areas of the surfaces of the silica gels treated at 400
      and 800 degrees C 4 and 8 weeks after implantation. X-ray diffraction analysis
      confirmed the presence of hydroxyapatite in these Ca-P-rich layers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7584875
TI  - Immunoblotting studies on artifactual contamination of enamel homogenates by
      albumin and other proteins.
AB  - The reason for the presence of albumin and other serum, cytoskeletal, cytosolic,
      and extracellular matrix proteins in enamel fractions was investigated by
      immunoblotting using homogenates prepared from freeze-dried and freshly dissected
      rat incisors, and antibodies capable of resolving at least 1 ng of the primary
      antigen. The data indicated that most of the 16 antibodies examined in this study
      reacted with antigens present only within "cell" homogenates (enamel organ cells
      + adhering labial connective tissue and blood vessels). One exception was rat
      serum albumin which was detected routinely in enamel homogenates prepared from
      freshly dissected, wiped incisors but rarely within enamel homogenates prepared
      from freeze-dried incisors. Another exception was calbindin-D 28 kDa which was
      consistently found within secretory stage enamel homogenates irrespective of
      preparative technique. A third exception was enamel proteins (amelogenins) which
      were enriched in secretory and early maturation stage enamel homogenates compared
      with cell homogenates and distributed as multiple molecular weight, antigenic
      bands in enamel homogenates (14-30 kDa), but mostly as a single antigenic band in
      cell homogenates (near 27 kDa). Overall, the results of this study suggest that
      developing rat incisor enamel naturally contains few exogenous proteins such as
      albumin. High concentrations of albumin (or other serum proteins) in crude
      homogenates, or purified fractions, derive mostly from blood and/or tissue fluids
      soaking into the enamel during sample preparation. This type of artifact can be
      avoided by using freeze-dried teeth for biochemical analyses.

PMID- 7584878
TI  - Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D
      receptor density.
AB  - We determined vitamin D receptor (VDR) gene alleles (based on the BsmI
      restriction site polymorphism), duodenal mucosal receptor density, bone mass at
      spine and total body, and body size in 32 healthy premenopausal females. While we
      found no relationship between allele and receptor density in duodenal mucosa,
      bone mineral content (BMC) at both spine and total body was significantly
      associated with VDR gene alleles. BMC was highest for the bb allele, lowest for
      BB, and intermediate for Bb. A similar association was noted between allele and
      body size variables, particularly weight. When BMC was adjusted for body weight,
      the association with VDR polymorphism disappeared. The VDR gene polymorphism may
      be affecting bone mass not through classical nutritional mechanisms (e.g.,
      intestinal calcium absorption), but through an influence on body size.

PMID- 7584879
TI  - Predictions on future diagnosis and treatment of osteoporosis: results and
      discussion of a recent opinion poll.

PMID- 7584883
TI  - Hints.
AB  - The systematic use of hints in the learning-from-examples paradigm is the subject
      of this review. Hints are the properties of the target function that are known to
      use independently of the training examples. The use of hints is tantamount to
      combining rules and data in learning, and is compatible with different learning
      models, optimization techniques, and regularization techniques. The hints are
      represented to the learning process by virtual examples, and the training
      examples of the target function are treated on equal footing with the rest of the
      hints. A balance is achieved between the information provided by the different
      hints through the choice of objective functions and learning schedules. The
      Adaptive Minimization algorithm achieves this balance by relating the performance
      on each hint to the overall performance. The application of hints in forecasting
      the very noisy foreign-exchange markets is illustrated. On the theoretical side,
      the information value of hints is contrasted to the complexity value and related
      to the VC dimension.

PMID- 7584880
TI  - Diet, bone mass, and osteocalcin: a cross-sectional study.
AB  - To determine the relationships among nutrients intake, bone mass, and bone
      turnover in women we have investigated these issues in a population-based, cross
      sectional, observational study in one county in central Sweden. A total of 175
      women aged 28-74 at entry to the study were included. Dietary assessment was made
      by both a semiquantitative food frequency questionnaire and by four 1-week
      dietary records. Dual energy X-ray absorptiometry was performed at five sites:
      total body, L2-L4 region of the lumbar spine, and three regions of the proximal
      femur. Serum concentrations of osteocalcin (an osteoblast-specific protein
      reflecting bone turnover) were measured by a radioimmunoassay. Linear regression
      models, with adjustment for possible confounding factors were used for
      statistical analyses. A weak positive association was found between dietary
      calcium intake as calculated from the semiquantitative food frequency
      questionnaire and total body bone mineral density (BMD) among premenopausal
      women. No association emerged between dietary calcium intake and site-specific
      bone mass, i.e., lumbar spine and femoral neck, nor was an association found
      between dietary calcium intake and serum osteocalcin. BMD at some of the measured
      sites was positively associated with protein and carbohydrates and negatively
      associated with dietary fat. In no previous studies of diet and bone mass have
      dietary habits been ascertained so carefully and the results adjusted for
      possible confounding factors. Neither of the two methods of dietary assessment
      used in this study revealed any effect of calcium intake on BMD at fracture
      relevant sites among these healthy, mostly middle-aged women.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7584881
TI  - Bone mass in androgen-insensitivity syndrome: response to hormonal replacement
      therapy.
AB  - The response of bone mass to long-term treatment with estrogen and progesterone
      in patients with complete androgen-insensitivity syndrome (AIS) is unknown. We
      report a 17-year-old female patient (karyotype 46 X, Y) with AIS studied during a
      4-year period. Bone mineral density (BMD) measured by dual X-ray absorptiometry
      in lumbar spine and proximal femur was sharply reduced at the initial visit; and
      remained unchanged during long-term follow-up on hormone replacement therapy with
      estrogens and progestin. Bone metabolism markers were all in the normal range.
      The lack of significant increase in BMD highlights the importance of androgens on
      bone physiology that cannot be balanced in spite of an appropriate estrogenic
      milieu.

PMID- 7584873
TI  - Parathyroid hormone decreases in vivo insulin effect on glucose utilization.
AB  - Hyperparathyroidism is associated with impaired glucose tolerance, and
      parathyroidectomy may improve carbohydrate homeostasis. It has been suggested
      that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear
      whether it also interferes with the peripheral action of insulin. To evaluate in
      vivo effects of PTH on insulin-mediated glucose utilization, 15 male Sprague
      Dawley rats were continuously infused with rat PTH (1-34) using an Alzet
      miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the
      vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were
      higher in the PTH-infused rats (12.3 +/- 0.2 versus 9.9 +/- 0.1 mg/dl, P < 0.01).
      On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a
      bolus infusion through the left femoral vein, blood samples were obtained from
      the right femoral vein, and plasma glucose and insulin were measured at basal (0
      minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose
      levels were higher (166 +/- 4 versus 155 +/- 4 mg/dL, P < 0.04) in the PTH
      infused rats but their insulin levels were similar to those of controls (6.5 +/-
      0.6 versus 5.6 +/- 0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and
      insulin levels were similar in both groups. However, although insulin levels were
      similar in both groups at all measured time points, glucose levels at 20 minutes
      were higher in the PTH-treated rats (205 +/- 13 versus 173 +/- 9; P <
      0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584882
TI  - Bone mineral density in patients with prostatic cancer treated with orchidectomy
      and with estrogens.
AB  - Bone mineral density (BMD) and bone mineral content (BMC) were measured in the
      femoral neck area, trochanteric area and Wards triangle, and in the distal radius
      of the left forearm before and after 1 year of endocrine treatment in 27 patients
      with prostatic cancer. Eleven of the patients were treated with orchidectomy and
      16 with combined oral and intramuscular estrogens. The patients were free from
      metastases during the entire observation period. In the orchidectomized patients,
      BMD and BMC of the distal radius decreased significantly following treatment,
      whereas no changes were observed in the estrogen-treated patients. These
      preliminary results demonstrate that estrogens may protect bone in male subjects
      also and may merit further investigations on larger groups of patients.

PMID- 7584884
TI  - Time-Skew Hebb rule in a nonisopotential neuron.
AB  - In an isopotential neuron with rapid response, it has been shown that the
      receptive fields formed by Hebbian synaptic modulation depend on the principal
      eigenspace of Q(0), the input autocorrelation matrix, where Qij(tau) = <xi i(t)
      xi j(t-tau)> and xi i(t) is the input to synapse i at time t (Oja 1982). We relax
      the assumption of isopotentiality, introduce a time-skewed Hebb rule, and find
      that the dynamics of synaptic evolution are determined by the principal
      eigenspace of Q. This matrix is defined by Qij = integral of 0 infinity (Qij *
      psi i) (tau) Kij (tau) d tau, where Kij (tau) is the neuron's voltage response to
      a unit current injection at synapse j as measured tau seconds later at synapse i,
      and psi(tau) is the time course of the opportunity for modulation of synapse i
      following the arrival of a presynaptic action potential.

PMID- 7584885
TI  - Synapse models for neural networks: from ion channel kinetics to multiplicative
      coefficient wij.
AB  - This paper relates different levels at which the modeling of synaptic
      transmission can be grounded in neural networks: the level of ion channel
      kinetics, the level of synaptic conductance dynamics, and the level of a scalar
      synaptic coefficient. The important assumptions to reduce a synapse model from
      one level to the next are explicitly exhibited. This coherent progression
      provides control on what is discarded and what is retained in the modeling
      process, and is useful to appreciate the significance and limitations of the
      resulting neural networks. This methodic simplification terminates with a scalar
      synaptic efficacy as it is very often used in neural networks, but here its
      conditions of validity are explicitly displayed. This scalar synapse also comes
      with an expression that directly relates it to basic quantities of synaptic
      functioning, and it can be endowed with meaningful physical units and realistic
      numerical values. In addition, it is shown that the scalar synapse does not
      receive the same expression in neural networks operating with spikes or with
      firing rates. These coherent modeling elements can help to improve, adjust, and
      refine the investigation of neural systems and their remarkable collective
      properties for information processing.

PMID- 7584887
TI  - A modular and hybrid connectionist system for speaker identification.
AB  - This paper presents and evaluates a modular/hybrid connectionist system for
      speaker identification. Modularity has emerged as a powerful technique for
      reducing the complexity of connectionist systems, and allowing a priori knowledge
      to be incorporated into their design. Text-independent speaker identification is
      an inherently complex task where the amount of training data is often limited. It
      thus provides an ideal domain to test the validity of the modular/hybrid
      connectionist approach. To achieve such identification, we develop, in this
      paper, an architecture based upon the cooperation of several connectionist
      modules, and a Hidden Markov Model module. When tested on a population of 102
      speakers extracted from the DARPA-TIMIT database, perfect identification was
      obtained.

PMID- 7584886
TI  - Generalization and analysis of the Lisberger-Sejnowski VOR model.
AB  - Lisberger and Sejnowski (1992) recently proposed a computational model for motor
      learning in the vestibular-ocular reflex (VOR) system. They showed that the
      steady-state gain of the system can be modified by changing the ratio of the two
      time constants along the feedforward and the feedback projections to the Purkinje
      cell unit in their model VOR network. Here we generalize their model by including
      two additional time constant variables and two synaptic weight variables, which
      were set to fixed values in their original model. We derive the stability
      conditions of the generalized system and thoroughly analyze its steady-state and
      transient behavior. It is found that the generalized system can display a
      continuum of behavior with the Lisberger-Sejnowski model and a static model
      proposed by Miles et al. (1980b) as special cases. Moreover, although
      mathematically the Lisberger-Sejnowski model requires two precise relationships
      among its parameters, the model is robust against small perturbations from the
      physiological point of view. Additional considerations on the gain of smooth
      pursuit eye movement, which is believed to share the positive feedback loop with
      the VOR network, suggest that the VOR network should operate in the parameter
      range favoring the behavior studied by Lisberger and Sejnowski. Under this
      condition, the steady-state gain of the VOR is found to depend on all four time
      constants in the network. The time constant of the Purkinje cell unit should be
      relatively small in order to achieve effective VOR learning through the
      modifications of the other time constants. Our analysis provides a thorough
      characterization of the system and could thus be useful for guiding further
      physiological tests of the model.

PMID- 7584888
TI  - Learning and generalization in radial basis function networks.
AB  - The two-layer radial basis function network, with fixed centers of the basis
      functions, is analyzed within a stochastic training paradigm. Various definitions
      of generalization error are considered, and two such definitions are employed in
      deriving generic learning curves and generalization properties, both with and
      without a weight decay term. The generalization error is shown analytically to be
      related to the evidence and, via the evidence, to the prediction error and free
      energy. The generalization behavior is explored; the generic learning curve is
      found to be inversely proportional to the number of training pairs presented.
      Optimization of training is considered by minimizing the generalization error
      with respect to the free parameters of the training algorithms. Finally, the
      effect of the joint activations between hidden-layer units is examined and shown
      to speed training.

PMID- 7584890
TI  - Methods for combining experts' probability assessments.
AB  - This article reviews statistical techniques for combining multiple probability
      distributions. The framework is that of a decision maker who consults several
      experts regarding some events. The experts express their opinions in the form of
      probability distributions. The decision maker must aggregate the experts'
      distributions into a single distribution that can be used for decision making.
      Two classes of aggregation methods are reviewed. When using a supra Bayesian
      procedure, the decision maker treats the expert opinions as data that may be
      combined with its own prior distribution via Bayes' rule. When using a linear
      opinion pool, the decision maker forms a linear combination of the expert
      opinions. The major feature that makes the aggregation of expert opinions
      difficult is the high correlation or dependence that typically occurs among these
      opinions. A theme of this paper is the need for training procedures that result
      in experts with relatively independent opinions or for aggregation methods that
      implicitly or explicitly model the dependence among the experts. Analyses are
      presented that show that m dependent experts are worth the same as k independent
      experts where k < or = m. In some cases, an exact value for k can be given; in
      other cases, lower and upper bounds can be placed on k.

PMID- 7584889
TI  - Patterns of functional damage in neural network models of associative memory.
AB  - Current understanding of the effects of damage on neural networks is rudimentary,
      even though such understanding could lead to important insights concerning
      neurological and psychiatric disorders. Motivated by this consideration, we
      present a simple analytical framework for estimating the functional damage
      resulting from focal structural lesions to a neural network model. The effects of
      focal lesions of varying area, shape, and number on the retrieval capacities of a
      spatially organized associative memory are quantified, leading to specific
      scaling laws that may be further examined experimentally. It is predicted that
      multiple focal lesions will impair performance more than a single lesion of the
      same size, that slit like lesions are more damaging than rounder lesions, and
      that the same fraction of damage (relative to the total network size) will result
      in significantly less performance decrease in larger networks. Our study is
      clinically motivated by the observation that in multi-infarct dementia, the size
      of metabolically impaired tissue correlates with the level of cognitive
      impairment more than the size of structural damage. Our results account for the
      detrimental effect of the number of infarcts rather than their overall size or
      structural damage, and for the "multiplicative" interaction between Alzheimer's
      disease and multi-infarct dementia.

PMID- 7584891
TI  - The Helmholtz machine.
AB  - Discovering the structure inherent in a set of patterns is a fundamental aim of
      statistical inference or learning. One fruitful approach is to build a
      parameterized stochastic generative model, independent draws from which are
      likely to produce the patterns. For all but the simplest generative models, each
      pattern can be generated in exponentially many ways. It is thus intractable to
      adjust the parameters to maximize the probability of the observed patterns. We
      describe a way of finessing this combinatorial explosion by maximizing an easily
      computed lower bound on the probability of the observations. Our method can be
      viewed as a form of hierarchical self-supervised learning that may relate to the
      function of bottom-up and top-down cortical processing pathways.

PMID- 7584893
TI  - An information-maximization approach to blind separation and blind deconvolution.
AB  - We derive a new self-organizing learning algorithm that maximizes the information
      transferred in a network of nonlinear units. The algorithm does not assume any
      knowledge of the input distributions, and is defined here for the zero-noise
      limit. Under these conditions, information maximization has extra properties not
      found in the linear case (Linsker 1989). The nonlinearities in the transfer
      function are able to pick up higher-order moments of the input distributions and
      perform something akin to true redundancy reduction between units in the output
      representation. This enables the network to separate statistically independent
      components in the inputs: a higher-order generalization of principal components
      analysis. We apply the network to the source separation (or cocktail party)
      problem, successfully separating unknown mixtures of up to 10 speakers. We also
      show that a variant on the network architecture is able to perform blind
      deconvolution (cancellation of unknown echoes and reverberation in a speech
      signal). Finally, we derive dependencies of information transfer on time delays.
      We suggest that information maximization provides a unifying framework for
      problems in "blind" signal processing.

PMID- 7584892
TI  - Spontaneous excitations in the visual cortex: stripes, spirals, rings, and
      collective bursts.
AB  - As a simple model of the cortical sheet, we study a locally connected net of
      spiking neurons. Refractoriness, noise, axonal delays, and the time course of
      excitatory and inhibitory postsynaptic potentials are taken into account
      explicitly. In addition to a low-activity state and depending on the synaptic
      efficacy, four different scenarios evolve spontaneously, viz., stripes, spirals,
      rings, and collective bursts. Our results can be related to experimental
      observations of drug-induced epilepsy and hallucinations.

PMID- 7584894
TI  - A perceptron reveals the face of sex.

PMID- 7584895
TI  - Self-organization as an iterative kernel smoothing process.
AB  - Kohonen's self-organizing map, when described in a batch processing mode, can be
      interpreted as a statistical kernel smoothing problem. The batch SOM algorithm
      consists of two steps. First, the training data are partitioned according to the
      Voronoi regions of the map unit locations. Second, the units are updated by
      taking weighted centroids of the data falling into the Voronoi regions, with the
      weighing function given by the neighborhood. Then, the neighborhood width is
      decreased and steps 1, 2 are repeated. The second step can be interpreted as a
      statistical kernel smoothing problem where the neighborhood function corresponds
      to the kernel and neighborhood width corresponds to kernel span. To determine the
      new unit locations, kernel smoothing is applied to the centroids of the Voronoi
      regions in the topological space. This interpretation leads to some new insights
      concerning the role of the neighborhood and dimensionality reduction. It also
      strengthens the algorithm's connection with the Principal Curve algorithm. A
      generalized self-organizing algorithm is proposed, where the kernel smoothing
      step is replaced with an arbitrary nonparametric regression method.

PMID- 7584896
TI  - On the distribution and convergence of feature space in self-organizing maps.
AB  - In this paper an analysis of the statistical and the convergence properties of
      Kohonen's self-organizing map of any dimension is presented. Every feature in the
      map is considered as a sum of a number of random variables. We extend the Central
      Limit Theorem to a particular case, which is then applied to prove that the
      feature space during learning tends to multiple gaussian distributed stochastic
      processes, which will eventually converge in the mean-square sense to the
      probabilistic centers of input subsets to form a quantization mapping with a
      minimum mean squared distortion either globally or locally. The diminishing
      effect, as training progresses, of the initial states on the value of the feature
      map is also shown.

PMID- 7584897
TI  - Sorting with self-organizing maps.
AB  - A self-organizing feature map (Von der Malsburg 1973; Kohonen 1984) sorts n real
      numbers in O(n) time apparently violating the O(n log n) bound. Detailed analysis
      shows that the net takes advantage of the uniform distribution of the numbers
      and, in this case, sorting in O(n) is possible. There are, however, an
      exponentially small fraction of pathological distributions producing O(n2)
      sorting time. It is interesting to observe that standard learning produced a
      smart sorting algorithm.

PMID- 7584898
TI  - Introducing asymmetry into interneuron learning.
AB  - A review is given of a new artificial neural network architecture in which the
      weights converge to the principal component subspace. The weights learn by only
      simple Hebbian learning yet require no clipping, normalization or weight decay.
      The net self-organizes using negative feedback of activation from a set of
      "interneurons" to the input neurons. By allowing this negative feedback from the
      interneurons to act on other interneurons we can introduce the necessary
      asymmetry to cause convergence to the actual principal components. Simulations
      and analysis confirm such convergence.

PMID- 7584899
TI  - Learning and generalization with Minimerror, a temperature-dependent learning
      algorithm.
AB  - We study the numerical performances of Minimerror, a recently introduced learning
      algorithm for the perceptron that has analytically been shown to be optimal both
      on learning linearly and nonlinearly separable functions. We present its
      implementation on learning linearly separable boolean functions. Numerical
      results are in excellent agreement with the theoretical predictions.

PMID- 7584901
TI  - The target switch algorithm: a constructive learning procedure for feed-forward
      neural networks.
AB  - We propose an efficient procedure for constructing and training a feed-forward
      neural network. The network can perform binary classification for binary or
      analogue input data. We show that the procedure can also be used to construct
      feedforward neural networks with binary-valued weights. Neural networks with
      binary-valued weights are potentially straightforward to implement using
      microelectronic or optical devices and they can also exhibit good generalization.

PMID- 7584900
TI  - Regularized neural networks: some convergence rate results.
AB  - In a recent paper, Poggio and Girosi (1990) proposed a class of neural networks
      obtained from the theory of regularization. Regularized networks are capable of
      approximating arbitrarily well any continuous function on a compactum. In this
      paper we consider in detail the learning problem for the one-dimensional case. We
      show that in the case of output data observed with noise, regularized networks
      are capable of learning and approximating (on compacta) elements of certain
      classes of Sobolev spaces, known as reproducing kernel Hilbert spaces (RKHS), at
      a nonparametric rate that optimally exploits the smoothness properties of the
      unknown mapping. In particular we show that the total squared error, given by the
      sum of the squared bias and the variance, will approach zero at a rate of n(
      2m)/(2m+1), where m denotes the order of differentiability of the true unknown
      function. On the other hand, if the unknown mapping is a continuous function but
      does not belong to an RKHS, then there still exists a unique regularized
      solution, but this is no longer guaranteed to converge in mean square to a well
      defined limit. Further, even if such a solution converges, the total squared
      error is bounded away from zero for all n sufficiently large.

PMID- 7584902
TI  - On the practical applicability of VC dimension bounds.
AB  - This article addresses the question of whether some recent Vapnik-Chervonenkis
      (VC) dimension-based bounds on sample complexity can be regarded as a practical
      design tool. Specifically, we are interested in bounds on the sample complexity
      for the problem of training a pattern classifier such that we can expect it to
      perform valid generalization. Early results using the VC dimension, while being
      extremely powerful, suffered from the fact that their sample complexity
      predictions were rather impractical. More recent results have begun to improve
      the situation by attempting to take specific account of the precise algorithm
      used to train the classifier. We perform a series of experiments based on a task
      involving the classification of sets of vowel formant frequencies. The results of
      these experiments indicate that the more recent theories provide sample
      complexity predictions that are significantly more applicable in practice than
      those provided by earlier theories; however, we also find that the recent
      theories still have significant shortcomings.

PMID- 7584903
TI  - LeRec: a NN/HMM hybrid for on-line handwriting recognition.
AB  - We introduce a new approach for on-line recognition of handwritten words written
      in unconstrained mixed style. The preprocessor performs a word-level
      normalization by fitting a model of the word structure using the EM algorithm.
      Words are then coded into low resolution "annotated images" where each pixel
      contains information about trajectory direction and curvature. The recognizer is
      a convolution network that can be spatially replicated. From the network output,
      a hidden Markov model produces word scores. The entire system is globally trained
      to minimize word-level errors.

PMID- 7584904
TI  - Koch's postulates and the digitalis-like factor.
AB  - Substantial, but still circumstantial evidence, supports strongly a role for a
      circulating digitalis-like factor in the pathogenesis of salt-sensitive
      hypertension. Although supported by many lines of evidence, this intriguing
      concept remains controversial, in large part because the responsible factor has
      proven to be very elusive. A very large number of candidates from a wide range of
      chemical classes have been proposed. Indeed, the large number of candidates, none
      supported by absolutely definitive evidence, has contributed to the controversy.
      In this essay, we have attempted to define the information that will be required
      before a candidate becomes widely accepted. Because the current situation
      resembles so strikingly the situation late in the nineteenth century--when
      efforts focused on the attempt to identify a specific micro-organism as the agent
      responsible for specific disease--we employed Koch's postulates as the organizing
      principle. The challenge faced by Robert Koch over a century ago is identical to
      the challenge that we face today.

PMID- 7584905
TI  - Nitroxidergic nerves and hypertension.
AB  - We studied vasodilator innervation in canine cerebral arteries and analyzed
      mechanisms of neurally induced vasodilatation. Available pharmacological,
      biochemical and histological evidence supports the hypothesis that nitric oxide
      (NO) synthesized in nerve terminals acts as a neurotransmitter that activates
      soluble guanylate cyclase in vascular smooth muscle and increases the production
      of cyclic GMP, resulting in relaxation. Peripheral arteries, such as the
      mesenteric, temporal, saphenous, uterine, and retinal, arteries, respond to nerve
      stimulation with contractions that are reversed to relaxations by alpha
      adrenoceptor blockade. The relaxation is also mediated by NO derived from
      perivascular nerves. Thus, reciprocal regulation by NO-mediated (nitroxidergic)
      and adrenergic nerves is speculated. Potentiation by NO synthase inhibitors of
      the arterial contraction associated with adrenergic nerve stimulation in vitro is
      ascribed to depressed vasodilator nerve function. Systemic blood pressure in
      anesthetized dogs is increased by intravenous injections of NO synthase
      inhibitors. Our evidence strongly suggests that the pressor response is
      associated with suppressed synthesis and release of NO derived mainly from
      vasodilator nerves. It is concluded that nitroxidergic vasodilator nerves play
      important roles in the regulation of vascular tone in vitro and in vivo and in
      the control of systemic blood pressure. Presented here are new concepts for the
      mechanism of hypertension and the role played by NO-mediated nerve function.

PMID- 7584907
TI  - Human urinary kallikrein can generate angiotensin II from homologous renin
      substrates.
AB  - We previously proposed the "kinin-tensin system," a unique vasoregulatory system
      that can produce both angiotensin II and kinins. To verify whether tissue
      kallikrein is a part of this system in humans, we examined the ability of human
      urinary kallikrein (HUK) to generate angiotensin (ANG) II directly from
      homologous renin substrates such as purified human angiotensinogen (AOGEN) and
      authentic human tridecapeptide renin substrate (13 RS). HUK released ANG II not
      only from ANG I but also directly from both AOGEN and 13RS at an optimum pH of
      7.0. The amount of generated ANG II from 7.5 nmol of each of the three substrates
      at pH 7.0 was as follows: ANG I, 292.7 +/- 67.2; 13 RS, 1951.7 +/- 239.6; AOGEN,
      2.2 +/- 0.3 (pmol/3h, n = 3 mean +/- SE). HUK cleaved Phe-His and His-Leu bonds
      in 13 RS, and Tyr-Ile and Phe-His bonds in ANG I. These results suggest that HUK
      is a part of the "kinintensin system", i.e., HUK can not only release kinins, but
      can also generate ANG II mainly through ANG I conversion and from AOGEN, the
      latter being a minor source of ANG II. Furthermore, HUK may play a role in
      regulating vascular tone under certain conditions in vivo.

PMID- 7584906
TI  - Percutaneous transluminal renal angioplasty in patients with renovascular
      hypertension: long-term results.
AB  - This study evaluated the long-term effects of percutaneous transluminal renal
      angioplasty (PTRA) on blood pressure and renal function in patients with
      renovascular hypertension. Seventy-eight patients with hypertension and
      unilateral or bilateral stenoses of the renal arteries (16 with fibromuscular
      dysplasia and 62 with atherosclerosis) were studied. All patients with
      fibromuscular dysplasia (group A) had normal renal function, while 27 of the 62
      patients with atherosclerosis (group B) presented with various degrees of renal
      failure. PTRA was technically successful in 87.5% patients of group A. The
      overall technical success rate (complete plus partial) was 72.3% (55/76 renal
      arteries) in group B. Mean follow-up (range) in months was 42 (12-108) for group
      A and 39 (13-106) for group B. After successful PTRA, the overall benefit rate
      (cure plus improved) for hypertension was 100% in group A; 10 of 14 patients were
      cured and 4 of 14 were improved. In group B, the overall benefit rate was 70.8%;
      9 of 48 were cured and 25 of 48 were improved. PTRA was technically successful in
      18 of 27 patients with renal failure. Renal function improved in 4 of 18
      patients, remained stable in 9 of 18, and deteriorated in 5 of 18 patients. The
      above results suggest that PTRA is an effective method for the long-term
      management of patients with renovascular hypertension, although the results were
      less favorable in the presence of bilateral renal artery stenoses: in addition to
      improved control of blood pressure, PTRA might improve renal function or delay
      its progressive deterioration.

PMID- 7584908
TI  - Systemic magnesium deficiency disclosed by magnesium loading test in patients
      with essential hypertension.
AB  - The present study was designed to determine whether magnesium (Mg) deficiency is
      present in patients with essential hypertension. We measured the retention of an
      intravenously administered Mg load (0.2 mmol/kg MgSO4 over 4 h), and serum and
      erythrocyte Mg concentrations in 17 inpatients with essential hypertension and in
      15 normotensive controls. There was no significant difference between the two
      groups in erythrocyte Mg concentration (normotensives vs., hypertensives: 2.0 +/-
      0.5 vs. 2.1 +/- 0.4 mmol/l cells), serum Mg concentration (normotensives vs.
      hypertensive: 2.1 +/- 0.2 vs. 2.1 +/- 0.2 mg/dl), or in urinary Mg excretion
      (normotensives vs. hypertensives: 65.8 +/- 25.5 vs. 73.7 +/- 26.7 mg/day).
      However, Mg retention was significantly higher in hypertensives than in
      normotensives (normotensives vs. hypertensives: 31.8 +/- 12.1 vs. 41.9 +/-
      13.3%). These results suggest that a systemic Mg deficiency, which is
      undectectable by serum or erythrocyte Mg determination, may exist in patients
      with essential hypertension.

PMID- 7584909
TI  - Changes in plasma endothelin-1 concentration during blood volume depletion and
      expansion: role of the cardiopulmonary baroreflex.
AB  - To study the relationship between blood volume and the plasma level of endothelin
      1 (ET-1), we examined the effects of blood volume depletion and expansion on the
      plasma ET-1 level in the rat. Anesthetized Wistar rats were subjected to
      hemorrhage (7 ml/kg), blood transfusion (7 ml/kg), or sham treatment. The same
      blood volume depletion and expansion were performed in other groups of rats,
      after bilateral cervical vagotomy or administration of intravenous atropine, to
      examine the role of the cardiopulmonary baroreflex. Hemorrhage produced mild
      decreases in the central venous pressure and arterial blood pressure, and an
      increase in the heart rate. Blood transfusion caused the opposite responses. The
      plasma ET-1 level was significantly higher in the volume-depleted rats (4.7 +/-
      0.4 pg/ml, mean +/- SE, p < 0.05 vs. control), and was lower in the volume
      expanded rats (2.6 +/- 0.2 pg/ml, p < 0.05) than in the control group (3.5 +/-
      0.3 pg/ml). In the vagotomized rats, the blood volume depletion decreased and the
      volume expansion increased the central venous pressure and the arterial pressure,
      but they did not change the heart rate or the plasma ET-1 level. Vagal efferent
      inhibition with atropine did not affect the volume-induced changes in the plasma
      ET-1 level. These results indicate that the plasma level of ET-1 increases with
      blood volume depletion, and decreases with volume expansion. The cardiopulmonary
      baroreflex may play an important role in the regulation of plasma ET-1 levels
      when the blood volume is altered.

PMID- 7584911
TI  - Effect of inhibition of nitric oxide synthesis on the cardiovascular and
      endocrine responses to hemorrhage in conscious rabbits.
AB  - Nitric oxide plays an important role in the regulation of arterial pressure by
      its actions to dilate vascular smooth muscle, alter sympathetic neural activity,
      and modulate the vasoconstrictor action of norepinephrine, angiotensin II and
      vasopressin. Nitric oxide may also influence blood pressure regulation by
      altering the secretion of renin and vasopressin. To test this possibility, we
      investigated the effects of inhibiting nitric oxide synthesis on the
      cardiovascular, renin and vasopressin responses to hypotensive hemorrhage, a
      situation in which the renin-angiotensin system and vasopressin contribute
      significantly to the control of blood pressure. Arterial blood was withdrawn from
      conscious, chronically-prepared rabbits at 1.0 ml/kg/min for 15 min under control
      conditions, and during i.v. infusion of the nitric oxide synthase inhibitor L
      NAME. Hemorrhage decreased mean arterial pressure from 69 +/- 2 to 45 +/- 4 mm Hg
      (p < 0.01) and increased heart rate from 211 +/- 10 to 270 +/- 15 bpm (p < 0.05).
      Plasma renin activity increased from 7.7 +/- 1 to 36.1 +/- 9.6 ng/ml/2h at 15 min
      (p < 0.01), while plasma vasopressin concentration increased from 1.7 +/- 0.6 to
      183.2 +/- 98.5 pg/ml (p < 0.05). Infusion of L-NAME increased blood pressure and
      plasma vasopressin concentration, and decreased heart rate and plasma renin
      activity. L-NAME markedly attenuated the hypotensive response to hemorrhage (72
      +/- 3 to 62 +/- 4 mmHg), but did not alter the increases in heart rate, plasma
      renin activity or plasma vasopressin concentration. In separate experiments, L
      NAME did not alter the setpoint or gain of the baroreceptor reflex control of
      heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584910
TI  - Effects of Ca-antagonists on oxidative susceptibility of low density lipoprotein
      (LDL).
AB  - Twelve adults (age 32-61 years) with essential hypertension were recruited from
      the outpatient clinics of National Defense Medical College hospital to serve as
      subjects in the present study. They were treated with nilvadipine, a Ca
      antagonist, 4 mg b.i.d. for 4 weeks. LDL samples were isolated by
      ultracentrifugation at the beginning (week 0) and at the end (week 4) of the
      treatment regimen. The formation of conjugated dienes was measured by incubating
      100 micrograms of LDL protein with 2 mumol CuSO4 in 2 ml phosphate buffered
      saline (PBS). There were no significant differences between lipids levels,
      composition and anti-oxidant levels of LDL at weeks 0 and 4. The lag time of LDL
      oxidation was 71.1 +/- 11.3 min at week 0 and 81.3 +/- 13.2 min at week 4 (p <
      0.05). In vitro studies of LDL oxidation, evaluated by thiobarbituric acid
      reactive substances (TBARS) and by agarose electrophoretic mobility, indicated
      that nilvadipine inhibited the oxidative modification of LDL while amlodipine,
      used as control, did not. Nilvadipine, a lipophilic Ca-antagonist, significantly
      prolonged the lag time of conjugated diene formation of LDL by 12.6% but
      amlodipine, a hydrophilic Ca-antagonist, had no major effect on LDL oxidation.
      These results suggest that Ca-antagonists are effective for the prevention of
      atherosclerosis but the effect is dependent upon the lipophilicity of the drugs.

PMID- 7584913
TI  - Effects of the non-peptide angiotensin II receptor antagonist TCV-116 on systemic
      and renal hemodynamics in dogs with renal hypertension.
AB  - The effects of TCV-116, a new non-peptide angiotensin II receptor antagonist, on
      systemic and renal hemodynamics were studied in conscious normotensive and renal
      hypertensive (2-kidney, 1-clip Gold-blatt type) dogs. When orally administered at
      0.03 to 1.0 mg/kg, TCV-116 inhibited the pressor response to angiotensin II in
      conscious normotensive dogs in a dose-dependent fashion. The IC50 and IC100
      values were 0.06 mg/kg and 0.86 mg/kg, respectively. TCV-116 at doses of 0.3
      mg/kg and 1.0 mg/kg dose-dependently and persistently decreased systolic and
      diastolic blood pressure in both dogs with acute renal (hyperreninemic) and those
      with chronic renal (normoreninemic) hypertension. Even a high dose of TCV-116 (10
      mg/kg, p.o.) increased effective renal plasma flow without affecting blood
      pressure or glomerular filtration rate in normotensive dogs. Furthermore, even at
      this high dose, TCV-116 did not reduce effective renal plasma flow or glomerular
      filtration rate in dogs with renal hypertension despite marked reduction in
      systemic blood pressure. The angiotensin converting enzyme inhibitor enalapril
      (10 mg/kg, p.o.) had renal hemodynamic effects similar to those of TCV-116. These
      findings indicate that TCV-116 has potent hypotensive effects not only in dogs
      with acute renal hypertension but also in those with chronic renal hypertension,
      but does not appear to adversely affect renal hemodynamics.

PMID- 7584914
TI  - Recent advances in the study of renin and angiotensinogen genes: from molecules
      to the whole body.
AB  - The renin-angiotensin system (RAS) plays a key role in the regulation of the
      circulation and is critically involved in the pathogenesis of several diseases,
      including hypertension. Renin is synthesized mainly in the kidney and is secreted
      into the bloodstream. It catalyzes the rate-limiting cleavage of substrate
      angiotensinogen, which is derived mainly from the liver, to generate angiotensin
      I. Renin and angiotensinogen genes have been isolated and their structure has
      been determined by the methods of molecular biology. Renin and angiotensinogen
      genes are expressed in many tissues, and the tissue-specific regulation of these
      genes has been studied. The existence of local RASs in contrast to the classical
      circulating RAS has been suggested, although their exact functional role remains
      to be determined. Recent molecular analyses have led to a detailed description of
      the transcriptional mechanism of the renin and angiotensinogen genes, and have
      made it possible to study the regulation of the expression of these genes in
      several physiological and pathological states. In addition, several types of
      transgenic animals have been developed to study the functional importance of the
      RAS in vivo. Transgenic mice with human renin and human angiotensinogen genes may
      be a good model of human hypertension. In such mice, the human genes are
      expressed in the normal tissue-specific pattern, the circulating RAS is
      activated, and blood pressure is high. Finally, angiotensinogen-deficient mice
      have also been developed by homologous recombination in mouse embryonic stem
      cells. These mice do not produce angiotensinogen in the liver. As a result, they
      have no plasma immunoreactive angiotensin I and are hypotensive. The profound
      hypotension in these mice indicates the importance of the RAS in maintaining
      pressure.

PMID- 7584916
TI  - Cerebral blood flow and brain function in hypertension.
AB  - In mild hypertensive patients, regional cerebral blood flow, measured by positron
      emission tomography, was reduced in the frontal cortex and basal ganglia compared
      with normotensive patients. In moderate to severe hypertensive patients, cerebral
      oxygen metabolism was diminished, although the patients were neurologically
      intact. In elderly hypertensives, white matter vascular lesions on brain imaging
      were more frequent and cognitive function was impaired, compared with age-matched
      normotensives. In nontreated spontaneously hypertensive rats (SHR), local
      cerebral blood flow was decreased in the cortex and thalamus, compared with
      normotensive rats (NTR). Spatial memory and learning in maze tests were more
      impaired in aged SHR than in old NTR or young SHR. This impairment was related to
      decreased cerebral glucose utilization in the medial septal nucleus, hippocampus,
      and other regions of the brain. Reduced cerebral blood flow, increased media
      thickness of the cerebral arteries and impaired cognitive function in SHR were
      improved by long-term antihypertensive treatment. In humans as well as animals,
      long-standing hypertension per se leads to reductions in cerebral blood flow,
      metabolism, and cognitive function, each of which possibly may be improved by
      controlling hypertension with long-term antihypertensive treatment.

PMID- 7584915
TI  - Patient-hospital relationship and quality of life in elderly patients with
      hypertension.
AB  - To investigate the influence of the patient-hospital relationship on the quality
      of life (QOL) and on medication compliance in elderly patients with hypertension,
      we developed a comprehensive scale for assessing the patient-hospital
      relationship. In the first phase, an original questionnaire consisting of 40
      items was designed under five fields for global assessment of the concept. We
      administered this questionnaire to 715 patients with cardiovascular diseases.
      Variations in the scores were evaluated by factor analysis. Three factors that
      comprised the majority of variance were derived by principal components analysis
      and varimax transformation. These orthogonal factors were considered to reflect
      "convenience of outpatient clinic", "satisfaction with clinical staff", and
      "communication with physician". We adopted three items under each of the three
      domains. Using this instrument, we assessed the patient-hospital relationship in
      402 elderly outpatients with hypertension at 8 clinical centers. QOL and
      medication compliance were simultaneously assessed. A linear regression analysis
      revealed a significant positive correlation between patient-hospital relationship
      and QOL scores (r = 0.403, p < 0.0001), which means that patient-hospital
      relationship explained up to 16% of the total variability in scores on the
      Overall Quality of Life scale. The medication compliance was also better in
      patients with higher scores on the Patient-Hospital Relationship scale. These
      results indicate that the patient-hospital relationship is one of the substantial
      factors determining QOL and medication compliance in elderly patients with
      hypertension.

PMID- 7584912
TI  - Gap junction protein locus on chromosome 18 cosegregates with body weight in the
      spontaneously hypertensive rat.
AB  - To detect genetic predisposing factors for hypertension, we screened the genome
      of the spontaneously hypertensive rat (SHR). We determined the genotypes of all
      F2 rats at polymorphic sites between the two strains, using the DNA of F2 rats
      derived from mating of SHR and Wistar-Kyoto rats (WKY). Cosegregation analysis
      was conducted to assess whether the genotypes of polymorphic markers associate
      with any phenotypic parameters such as directly measured blood pressure, heart
      rate or body weight. All measurements in F2 rats were performed at 15 weeks of
      age. Two polymorphic markers on chromosome 18 cosegregated with body weight. Gap
      junction protein (heart connexin 43) gene showed the most significant association
      with body weight as a recessive trait, but no association was noted with other
      parameters. We conclude that the gap junction protein locus is a new candidate
      for the determinant gene of body weight in SHR.

PMID- 7584919
TI  - Role of cathepsin B as prorenin processing enzyme in human kidney.
AB  - Renin is synthesized from an inactive precursor, prorenin, through cleavage at a
      pair of basic amino acids catalyzed by prorenin processing enzyme (PPE). A
      lysosomal protease, cathepsin B, has been suggested to be a strong candidate for
      PPE. However, there still remains a possibility that other protease(s) can also
      catalyze prorenin processing. We studied the subcellular distribution of PPE in
      human renal cortex using pure recombinant prorenin as a PPE assay substrate. PPE
      and renin activities, and cathepsin B activity and protein were colocalized in
      the lysosomal fraction. The PPE activity was completely inhibited by a cathepsin
      B specific inhibitor, CA074. Taken together with the immunohistochemical data
      showing that cathepsin B and PPE are colocalized in dense secretory granules of
      juxtaglomerular cells of kidney, we conclude that cathepsin B is the authentic
      PPE in human kidney.

PMID- 7584918
TI  - Differential effects of an alpha 1-blocker (doxazosin) on diurnal blood pressure
      variation in dipper and non-dipper type hypertension.
AB  - A study was conducted to determine whether sympathetic nerve activity, one of the
      main regulators of blood pressure, is involved in high blood pressure in the
      night-time and morning. Twenty-seven untreated hypertensive subjects, in whom
      hypertension was diagnosed by ambulatory blood pressure (ABP) measurement, who
      showed a 24 h systolic ABP value over 140 mmHg and/or 24 h diastolic ABP over 90
      mmHg were recruited. They also showed a night-time systolic ABP value of over 130
      mmHg and/or a night-time diastolic ABP of over 80 mmHg. They were divided into
      two groups: "dippers (D)" whose night-time ambulatory blood pressure fell by more
      than 10% of the day-time blood pressure, and "non-dippers (ND)" in whom this
      phenomenon was absent. We examined the effect of a long-acting alpha 1-blocker
      (doxazosin) on diurnal blood pressure variation in these subjects with essential
      hypertension. Baseline casual blood pressure and 24 h systolic ABP were not
      significantly different between the two groups. However, both night-time and
      morning ABP in ND were higher than those in D. Administration of doxazosin (mean
      73 +/- 13 (SE) d) significantly decreased casual blood pressure, and 24 h, day
      time, night-time and morning systolic ABP in the whole cohort. When subjects were
      divided into D and ND, the day-time and morning systolic ABP decreased
      significantly after doxazosin treatment in both groups, whereas the night-time
      systolic ABP decreased significantly only in ND but not in D. These results
      suggest that sympathetic nerve activity involved in elevating blood pressure
      during the night may differ between D and ND.

PMID- 7584917
TI  - Differences in ischemic threshold and nitrate efficacy between normotensive and
      hypertensive patients with stable angina pectoris.
AB  - The coexistence of ischemic heart disease with hypertension makes
      antihypertensive therapy essential, since relief of hypertension may ameliorate
      the coronary disease. On the other hand, the effect of antianginal nitrate
      therapy in patients with stable angina pectoris and systemic arterial
      hypertension is not fully understood. This study assessed the effects of
      hypertension on the ischemic threshold and the time to moderate angina, measured
      as parameters of nitrate efficacy. In this double-blind, parallel-group study,
      141 patients with stable angina pectoris were randomly assigned to receive 5 mg,
      10 mg or 20 mg isosorbide-5-mononitrate or matching placebo bid for 21 days.
      Ninety-three normotensive and 48 hypertensive patients were compared with regard
      to the time to moderate anginal pain and the ischemic threshold before and after
      nitrate treatment on the first day of the study. The acute nitrate effect 2 h
      after drug administration was substantially attenuated in hypertensives at both
      10 and 20 mg of isosorbide-5-mononitrate, with the time to moderate anginal pain
      being significantly shortened. Impaired vasodilatator response of the arterial
      vasculature to organic nitrates, probably due to impaired biotransformation of
      organic nitrates to nitric oxide in hypertensive patients, is suggested as a
      possible mechanism for the diminished nitrate effect. Thus, oral nitrate therapy
      does not have the same beneficial antianginal effect in hypertensive patients as
      it does in normotensives. Dose adjustment based on the pretreatment blood
      pressure, and the administration of higher doses of oral nitrates should
      therefore be considered in hypertensive patients suffering from stable angina
      pectoris.

PMID- 7584921
TI  - Effects of intracerebroventricular infusion of Fab fragments of digoxin antibody
      (Digibind) on development of reduced renal mass-saline hypertension in rats.
AB  - To clarify the role of brain ouabain-like compound in reduced renal mass-saline
      hypertension, we examined the effects of intracerebroventricular infusion of the
      Fab fragments of antidigoxin antibody (Digibind) on the change in blood pressure
      of saline-drinking subtotally nephrectomized rats. Twenty male Wistar rats
      weighing 250 g each underwent subtotal nephrectomy. Two groups of 10 rats
      received intracerebroventricular infusion of Digibind (20 mg/ml) or normal sheep
      IgG (20 mg/ml) at a rate of 0.5 microliters/h for 11 days. All rats began to
      drink 1% NaCl solution after two days of infusion. Systolic blood pressure was
      measured by the tail-cuff method on days 2, 6 and 9 of infusion. Two groups of
      saline-drinking rats with reduced renal mass developed hypertension. However,
      systolic blood pressure was significantly higher in Digibind-infused rats than in
      IgG-infused rats (day 2, 144 +/- 3(SEM) vs. 133 +/- 1 mmHg, p < 0.05; day 6, 161
      +/- 4 vs. 151 +/- 2 mmHg, 0.05 < p < 0.1, day 9, 181 +/- 8 vs. 155 +/- 2 mmHg, p
      < 0.05). In spite of similar renal dysfunction, plasma aldosterone
      concentrations, and plasma OLC levels, the accelerated increase in blood pressure
      was accompanied by a significantly impaired pressure-natriuresis relationship
      (0.089 +/- 0.013 vs. 0.131 +/- 0.013 mmol/day/mmHg, p < 0.05). These results
      indicate that chronic intracerebroventricular infusion of Digibind augmented
      reduced renal mass-saline hypertension in rats and suggest that brain ouabain
      like compound may play a protective role against the elevation of blood pressure,
      at least in this model of hypertension.

PMID- 7584920
TI  - Prolonged inhibition of neutral endopeptidase 24.11 by sinorphan in stroke-prone
      spontaneously hypertensive rats.
AB  - The cardiovascular consequences of inhibition of the neutral endopeptidase 24.11
      (NEP) with the orally active NEP inhibitor sinorphan were evaluated by
      determining long-term effects of the drug on hemodynamic, hormonal and structural
      parameters in stroke-prone spontaneously hypertensive rats (SHR-SP). Systolic
      blood pressure increased in young SHR-SP from 194 +/- 2 to 266 +/- 7 mmHg,
      whereas in sinorphan (30 mg/kg p.o. bid) treated animals systolic blood pressure
      increased only from 193 +/- 4 to 229 +/- 4 mmHg during the treatment period of 9
      weeks. The increase in relative heart weight was also delayed. Plasma ANP was
      higher in the sinorphan group than in the controls. The results of a second study
      demonstrate a substantial improvement of cardiac pump function and ventricular
      hypertrophy in old SHR-SP with compromised cardiac function by long-term
      inhibition of NEP. Thirteen-month-old SHR-SP were treated with sinorphan (30
      mg/kg p.o. bid) for two weeks. At the end of experiment, the increase in ANP
      plasma levels did not reach statistical significance, whereas plasma cGMP was
      higher in sinorphan treated animals than in controls. Left ventricular end
      diastolic pressure was markedly elevated in controls and significantly lower in
      sinorphan treated animals. In addition, sinorphan reduced cardiac hypertrophy in
      these old SHR-SP. In conclusion, the results of the present studies demonstrate
      that long-term NEP inhibition with sinorphan has inhibitory effects on malignant
      hypertension and associated cardiac hypertrophy in young SHR-SP on a high-sodium
      diet. NEP inhibition substantially improves cardiac pump function and reduces
      ventricular hypertrophy of old SHR-SP with compromised cardiac function.

PMID- 7584922
TI  - Left ventricular geometry and cardiac function in mild to moderate essential
      hypertension.
AB  - To elucidate left ventricular (LV) cardiac structure and function in patients
      with mild to moderate essential hypertension, we studied the relationship between
      LV geometry and function. We evaluated LV diastolic and systolic functions by M
      mode echocardiography in 91 age-matched normotensive control subjects (NT) and
      124 patients with essential hypertension. Hypertensive patients were divided into
      two groups based on the WHO stage classification: WHO I (n = 76) and WHO II (n =
      48). Patients in WHO I and WHO II were further categorized according to the
      relative wall thickness as normal left ventricle (n = 47), concentric remodeling
      (n = 29), concentric hypertrophy (n = 25), and eccentric hypertrophy (n = 23). LV
      diastolic function was significantly decreased in the hypertensive groups
      compared to NT. There was no significant difference in LV systolic performance
      among NT, WHO I and WHO II. LV contractility was significantly increased in WHO I
      compared to NT. In respect to ventricular geometric pattern, LV diastolic
      function was significantly decreased in both the concentric hypertrophy and
      eccentric hypertrophy groups. LV systolic dysfunction was noted only in the
      eccentric hypertrophy group. In conclusion, patients with concentric remodeling
      had normal systolic and diastolic functions. LV diastolic function was impaired
      in both the concentric and eccentric hypertrophy groups due to an increase in
      LVMi. Moreover, LV systolic impairment was noted in the eccentric hypertrophy
      group due to an inappropriate compensation to LV systolic load.

PMID- 7584923
TI  - Exercise-induced secretion of brain natriuretic peptide in essential hypertension
      and normal subjects.
AB  - To determine the major stimuli for the release of brain natriuretic peptide (BNP)
      and atrial natriuretic peptide (ANP), we measured their plasma concentrations in
      14 normal subjects and 19 patients with essential hypertension during exercise
      with a bicycle ergometer. The plasma levels of both hormones at baseline were
      significantly higher in the hypertensive group than in the controls (p < 0.05).
      The exercise raised both the plasma BNP and ANP, with concomitant increases in
      systolic blood pressure (SBP), heart rate (HR) and plasma norepinephrine (NE) or
      epinephrine (Epi) in each group. In the controls the change in ANP correlated
      with those in SBP, HR and NE (p < 0.05), and similarly the change in BNP with
      those in SBP, HR, NE and Epi (p < 0.05). In multivariate regression analysis only
      NE was found to be a significant stimulus for ANP secretion, whereas SBP or Epi
      was related to BNP release. In the hypertensives the change in ANP correlated
      with those in HR and NE, but on multivariate regression analysis the change in
      ANP correlated only with that in HR. The change in BNP in the hypertensives
      correlated only with that in HR. These findings indicate that in normal subjects
      the exercise-induced release of BNP and ANP is more sensitive to a similar but
      slightly different sympathetic stimulus, whereas in hypertensives the major
      stimulus for the release of both hormones is heart rate, indicating that the
      mediators for BNP or ANP release are altered by some factors involved in
      hypertension.

PMID- 7584924
TI  - Endothelium-dependent responses in hypertension.
AB  - The endothelium controls the tone of the underlying vascular smooth muscle by
      releasing relaxing factors. These include prostacyclin, nitric oxide (NO), and
      endothelium-derived hyperpolarizing factor (EDHF). In certain types of
      hypertension, endothelium-dependent relaxations are curtailed, because of a
      reduced production and/or action of endothelium-derived NO and EDHF. In the
      spontaneously hypertensive rat, endothelium-dependent relaxations are reduced,
      because of the endothelium-dependent production of vasoconstrictor prostanoids
      (endoperoxides and, in some cases, thromboxane A2). These prostanoids may be
      produced in the vascular smooth muscle cells rather than in the endothelium. The
      endothelial dysfunction observed in hypertensive blood vessels is likely to be a
      consequence rather than a cause of the disease process.

PMID- 7584925
TI  - The role of the autonomic nervous system in hypertension.
AB  - The role of the autonomic nervous system in the genesis and maintenance of
      hypertension is becoming clearer with time. Early research suggested that
      increased vascular resistance in hypertension was not dependent on excess
      autonomic tone and thus it was presumed that the autonomic nervous system had
      little to do with hypertension. More recent studies have demonstrated that the
      initial hemodynamic abnormality in hyperkinetic borderline hypertension is
      "normal" vascular resistance, with an elevated cardiac optput and heart rate,
      associated with markers of increased sympathetic and decreased parasympathetic
      tone of central origin. Over time there is a transition to the high peripheral
      resistance and normal cardiac output hemodynamic state characteristic of
      established hypertension, which is due to the development of adaptive structural
      changes in the peripheral resistance vessels and heart. The autonomic abnormality
      in hypertension and subsequent vascular and cardiac changes may explain some of
      association between hypertension and risk factors for coronary heart disease. The
      autonomic imbalance found in hypertension may not be a chance occurrence and we
      postulate that it is due to the inheritance of the genes responsible for a more
      pronounced defense reaction, which in earlier times may have conferred a survival
      advantage but now permit the negative impact of this trait to become evident.

PMID- 7584926
TI  - Endocrine and auto-paracrine factors in the pathogenesis of primary hypertension.
AB  - Referring to the mosaic theory of Page, the authors present an overview of recent
      topics related to the participation of endocrine and auto-paracrine factors, such
      as steroids, ouabain-like substance, insulin, renin-angiotensin and endothelin,
      in the pathogenesis of primary hypertension. These factors promote the
      development of hypertension in either a direct or indirect manner; in addition,
      they promote, to some extent, the proliferation of vascular smooth muscle cells.
      Future research should attempt to elucidate interactions between these factors in
      cardiovascular tissues and to define how these factors interact with various
      vasodepressor substances to regulate blood pressure.

PMID- 7584927
TI  - Framingham study insights into hypertensive risk of cardiovascular disease.
AB  - Elevated blood pressure is a common and powerful predisposing factor for stroke,
      coronary disease, cardiac failure and peripheral artery disease imposing a 2-3
      fold increased risk of one or more of these atherosclerotic sequelae. The risk
      ratio imposed by hypertension is greatest for cardiac failure and stroke, but in
      Western countries coronary disease is the most common and lethal hazard. In
      hypertensive men and women respectively, 35% and 45% of myocardial infarctions
      are silent or unrecognized necessitating routine periodic ECG examination for its
      detection. Comparison of the impacts of systolic and diastolic blood pressure
      gives no indication of a greater impact of diastolic pressure and isolated
      systolic hypertension is distinctly hazardous. Over-reliance on diastolic
      pressure to assess risk can be misleading, particularly in advanced age.
      Attributable risk estimates suggest that 78% of hypertension in men and 65% in
      women is directly attributable to adiposity, making weight control of paramount
      importance for primary prevention of hypertension. The likelihood of development
      of cardiovascular disease in the hypertensive patient is greatly enhanced by the
      presence of metabolically-linked risk factors and already existent cardiovascular
      conditions. These influence the urgency and choice of therapy. Rational and
      efficient assessment of the hypertensive candidate for cardiovascular disease
      requires use of a cardiovascular risk profile evaluating the joint effect of
      multiple risk factors and effective treatment improves multivariate risk.

PMID- 7584928
TI  - Effect of moderately increased intrapelvic pressure on renal tissue pressure and
      vasopressin release in rabbits.
AB  - Electrical stimulation of afferent renal nerves and activation of intrarenal
      receptors increases plasma vasopressin concentration, but the role of afferent
      renal nerves in the control of vasopressin secretion is not clear. Recently, we
      reported that activation of renal mechanoreceptors stimulates the release of
      vasopressin. However, intrapelvic pressure was increased to 50 mmHg, and this
      increase is above the normal physiological range. Therefore, in the present
      study, we investigated the effect of moderately increased intrapelvic pressure on
      plasma vasopressin concentration in anesthetized rabbits. First, we measured
      renal tissue pressure while intrapelvic pressure was increased stepwise in 10
      mmHg increments. Basal renal tissue pressure was 17 +/- 2 mmHg. Renal tissue
      pressure increased only when intrapelvic pressure was higher than the basal
      tissue pressure of each animal. Usually, increases in intrapelvic pressure less
      than 20 mmHg did not increase renal tissue pressure. This finding suggests that
      only increases in intrapelvic pressure more than 20 mmHg can activate renal
      mechanoreceptors. Based on this finding, the effects of moderate increases in
      intrapelvic pressure (15 and 30 mmHg) were studied. With a 15-mmHg increase in
      intrapelvic pressure, plasma vasopressin concentration did not change
      significantly. However, when intrapelvic pressure was increased to 30 mmHg,
      plasma vasopressin concentration increased from 5.6 +/- 1.4 to 9.5 +/- 2.8 pg/ml
      at 5 min (p < 0.05) and to 8.8 +/- 2.0 pg/ml at 10 min (p < 0.05). Plasma renin
      activity and mean arterial pressure also increased when intrapelvic pressure was
      increased to 30 mmHg. We conclude that moderate increases in intrapelvic pressure
      stimulate vasopressin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7584929
TI  - Recombinant human erythropoietin stimulates tubular reabsorption of sodium in
      anesthetized rabbits.
AB  - To determine whether recombinant human erythropoietin (rHuEPO) exerts a direct
      vasoconstrictive effect on renal arteries or affects renal function, we measured
      renal hemodynamics and renal function during a 30-min intrarenal infusion of
      rHuEPO in anesthetized rabbits without renal failure. Intrarenal infusion of
      rHuEPO at a rate of 100 U/min did not alter mean arterial pressure, renal blood
      flow, or renal vascular resistance, as compared with controls treated with
      vehicle. There were no significant rHuEPO-associated changes in glomerular
      filtration rate, filtration fraction, or arterial hematocrit. However, urine
      volume, urinary excretion of sodium and potassium, and fractional sodium
      excretion were significantly reduced by intrarenal infusion of rHuEPO. These
      observations indicate that rHuEPO has no direct effects on mean arterial pressure
      or renal hemodynamics, but that it stimulates net tubular sodium reabsorption,
      and reduces urine volume and urinary excretion of sodium and potassium in
      anesthetized rabbits without renal failure.

PMID- 7584930
TI  - Seasonal variation in 24-h blood pressure pattern of young normotensive women.
AB  - To investigate the seasonal variations in ambulatory blood pressure patterns, 24
      h blood pressure was measured every 15 minutes noninvasively in ten young
      normotensive women. Urine was collected every 4 hours. The examinations were
      repeated in spring, summer, autumn, and winter in a standardized living
      environment. The 24-h average systolic and diastolic blood pressures did not
      differ significantly among the seasons. Similarly, there were no significant
      differences in the average values of either daytime or nighttime blood pressure.
      In contrast, the average pulse rate during nighttime was significantly higher in
      winter than in summer (64 +/- 2 beats/min vs. 59 +/- 2 beats/min, p < 0.05). The
      variabilities of either blood pressure or pulse rate did not change significantly
      among the seasons. The mesors and acrophases of both systolic and diastolic blood
      pressures, determined by a single cosinor method, were not significantly
      different among the seasons. On the other hand, the acrophase of pulse rate
      appeared significantly later in winter (16:19) compared with those in spring
      (14:54), summer (14:42), and autumn (14:21). Urine volume and urinary excretion
      of norepinephrine were significantly greater in winter than in summer. These
      results indicate that the 24-h pattern of blood pressure is reproducible and
      shows no seasonal difference in young normotensive women.

PMID- 7584931
TI  - Insulin receptor gene polymorphism and hyperinsulinemia in hypertensive patients.
AB  - Although insulin resistance often occurs in association with hypertension,
      considerable variation is observed in the degree of insulin resistance among
      hypertensive patients. Since there is evidence of a genetic basis in the
      development of insulin resistance in hypertension, we analyzed the contribution
      of genetic factors to insulin resistance in hypertensive patients. Sixty-six
      Japanese hypertensive patients were studied. These patients were divided into two
      groups (hyperinsulinemia group and normoinsulinemia group) according to plasma
      insulin response during a 75-g oral glucose tolerance test (75g-OGTT). Insulin
      receptor gene (INSR) was studied for association with insulin resistance in
      hypertensive patients. A microsatellite polymorphism in intron-2 of the insulin
      receptor gene was analyzed by the polymerase chain reaction method. Five alleles
      were detected in the INSR microsatellite. The frequency of C/C genotype in the
      hyperinsulinemia group was significantly higher than that in the normoinsulinemia
      group (73% vs. 43%, p = 0.02). There was no difference in genotype frequency of
      INSR between hypertensive patients and control subjects. When the hypertensive
      patients were divided into two groups, the frequency of C/C genotype in the
      hyperinsulinemia group was significantly higher than that in the control group
      (73% vs. 45%, p = 0.014). There was no significant difference between the
      normoinsulinemia group and control group. These data suggest that the insulin
      receptor gene may contribute to insulin resistance in hypertensive patients with
      hyperinsulinemia.

PMID- 7584932
TI  - Pharmacodynamics of atrial natriuretic peptide in isolated perfused Dahl rat
      kidneys.
AB  - Atrial natriuretic peptide (ANP) has been implicated in the development of
      hypertension in Dahl R and S rats. To test the responses of DR and DS kidneys in
      the absence of the influence of neural and humoral mechanisms, we investigated
      the pharmacokinetics and pharmacodynamics of ANP in isolated perfused DR and DS
      kidneys, obtained from rats given a high or low sodium diet, after a bolus
      injection of ANP (1 microgram) or after a bolus injection plus infusion of ANP to
      maintain the perfusate concentration at 1000 pg/ml. The elimination rate constant
      was not different between the groups (DR, 0.044 min-1 vs. DS, 0.050 min-1).
      Clearance of ANP was 4 times greater than the glomerular filtration rate,
      indicating that a receptor-mediated peritubular clearance is probably the primary
      route of elimination. DS kidneys excreted 50% less sodium than DR kidneys.
      However, ANP caused a 5-fold increase in fractional sodium excretion in both DR
      and DS. ANP also increased sodium excretion, creatinine clearance, and urine
      flow. No alteration in ANP kinetics occurred to account for the reportedly
      increased circulating concentrations of ANP seen in DS rats. We conclude that
      isolated DR and DS kidneys respond differently to ANP after bolus ANP
      administration to concentrations of 10,000 pg/ml. This difference in response is
      due to the sodium excretory defect inherent in the DS kidney and not to an
      alteration in the DS kidney's ANP responsiveness.

PMID- 7584933
TI  - Effects of intra-arterial infusion of insulin on forearm vasoreactivity in
      hypertensive humans.
AB  - We previously demonstrated that intra-arterial infusion of insulin attenuates
      vasoreactivity to phenylephrine and angiotensin II in the forearm of normotensive
      humans, which suggests that the pressor effects of insulin via sympathetic
      activation may be offset in peripheral arteries. In the present study, we
      investigated the effects of insulin on vasoreactivity in hypertensive humans.
      Seven male patients with essential hypertension (age, 26 +/- 2 yr; blood
      pressure, 159 +/- 4/103 +/- 4 mmHg; mean +/- SEM) were studied. We measured
      forearm blood flow by a strain gauge plethysmograph while infusing phenylephrine
      (1, 4, 12 nmol/min) and angiotensin II (5, 10, 20 pmol/min) locally into the
      brachial artery before and during simultaneous intra-arterial infusion of human
      insulin (0.15 mU/kg/min). Forearm vascular resistance was calculated from
      directly measured arterial pressure and forearm blood flow. Intra-arterial
      infusion of insulin raised the local plasma insulin level without changing the
      blood glucose level, basal forearm blood flow, or forearm vascular resistance.
      Phenylephrine and angiotensin II increased forearm vascular resistance dose
      dependently before and during insulin infusion. In contrast to the previous
      results in normotensive subjects, locally infused insulin did not attenuate
      vasoconstrictive responses to phenylephrine and angiotensin II in patients with
      essential hypertension. These results suggest that the balance between the
      pressor and depressor effects of insulin might be altered in favor of a pressor
      effect in patients with hypertension.

PMID- 7584936
TI  - A unique case of renovascular hypertension caused by combined renal artery
      disease.
AB  - We present a unique case of renovascular hypertension due to combined renal
      artery disease in a 22-year-old woman. Renal angiography revealed renal artery
      stenosis with poststenotic dilatation and an aneurysm due to fibromuscular
      dysplasia in the left kidney, and a congenital arteriovenous fistula in the right
      kidney. The results of a captopril test and plasma renin sampling demonstrated
      that the renin-angiotensin-aldosterone system was stimulated in both kidneys,
      accounting for the hypertension in this patient. Almost all cases of renovascular
      hypertension are due to only one underlying renal artery disease. This is the
      first case of renovascular hypertension associated not only with renal artery
      stenosis and an aneurysm due to fibromuscular dysplasia, but also with a
      congenital arteriovenous fistula.

PMID- 7584935
TI  - Possible linkage between renal injury and cardiac remodeling in Dahl salt
      sensitive rats treated with the calcium channel antagonist benidipine.
AB  - Interest in cardiovascular protection by calcium channel antagonists has grown
      over the past decade. We investigated the prevention of cardiac remodeling and
      renal injury by the long-acting calcium channel antagonist benidipine using 12
      week-old Dahl salt-sensitive (Dahl S) rats fed a high-salt (4% NaCl) diet. Six
      week benidipine treatment (10 mg/kg chow) decreased systolic blood pressure by
      22% in Dahl S rats. This blood pressure reduction was associated with decreases
      in cardiac mass and weight of the aortic wall. Collagen content in the left
      ventricle tended to decline with benidipine treatment. In addition, glomerular
      filtration rate increased by 33% and arterial and glomerular lesions improved
      morphologically with this treatment. Regression of cardiac mass and collagen
      content in the left ventricle was due mainly to blood pressure reduction;
      however, collagen content in the low-pressure right ventricle was not only
      related to systemic blood pressure but to the severity of renal lesions. These
      data suggest that the calcium channel antagonist benidipine attenuates cardiac
      and renal injury in hypertensive Dahl S rats, and that part of the cardiac
      hypertrophy is due to a non-hemodynamic mechanism that might be responsible for,
      or be a consequence of, the lesions in the kidney.

PMID- 7584934
TI  - A 12-month comparison of ACE inhibitor and CA antagonist therapy in mild to
      moderate essential hypertension--The GLANT Study. Study Group on Long-term
      Antihypertensive Therapy.
AB  - Patients with mild to moderate essential hypertension were treated mainly with an
      ACE inhibitor (delapril, n = 980) or a Ca antagonist (n = 956) for 12 months, and
      the incidence of cerebrovascular and cardiovascular events as well as drug
      related side effects were compared between the two groups. There were no
      significant differences between the clinical backgrounds of the two groups. In
      both groups, the blood pressure was decreased significantly from 1 month of
      treatment onwards, with the degree of reduction being greater in the Ca
      antagonist group throughout the study period (p < 0.001). Cerebrovascular or
      cardiovascular events occurred in 11 out of 980 patients in the delapril group
      and 18 out of 956 patients in the Ca antagonist group (p = NS). Cerebrovascular
      disease developed in 5 delapril-treated patients and 11 Ca antagonist-treated
      patients, and heart disease developed in 5 and 7 patients, respectively (both p =
      NS). Discontinuation of treatment due to side effects was significantly more
      common in the delapril group than in the Ca antagonist group (p < 0.001). There
      was no significant difference in the incidence of cerebrovascular and
      cardiovascular events between the two groups, and the results suggested that
      blood pressure reduction per se did not necessarily lead to a parallel decrease
      in cerebrovascular and cardiovascular complications.

PMID- 7584937
TI  - Molecular medicine in a changing world.

PMID- 7584938
TI  - Clinical trials in Japan.

PMID- 7584939
TI  - Too many scientists, too few academic jobs.
AB  - Graduate education in the sciences is not doing its job. By preparing students
      only for academic research, the system neglects the range of opportunities for
      work in science that young scientists want and society needs.

PMID- 7584941
TI  - Lesion versus lumen.

PMID- 7584942
TI  - The form and the substance.

PMID- 7584943
TI  - Human embryo research deserves public support.

PMID- 7584940
TI  - The gene as the drug.

PMID- 7584944
TI  - Hypersensitivity to nonsteroidal anti-inflammatory drugs.

PMID- 7584945
TI  - An opportunity in organ transplantation.
AB  - Further progress in organ transplantation must overcome two key problems: a
      shortage of organs and long term immunological tolerance. Xenografts and
      immunological conditioning may help.

PMID- 7584947
TI  - A question of culture.

PMID- 7584946
TI  - Many roads lead to atheroma.
AB  - For many years cholesterol was seen as the worst enemy of coronary arteries.
      Recent advances show that interactions between lipoproteins, coagulation and
      growth factors are important in atherosclerosis.

PMID- 7584948
TI  - Coxsackieviruses and diabetes.

PMID- 7584949
TI  - Angiogenesis in cancer, vascular, rheumatoid and other disease.
AB  - Recent discoveries of endogenous negative regulators of angiogenesis,
      thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor,
      all associated with neovascularized tumours, suggest a new paradigm of
      tumorigenesis. It is now helpful to think of the switch to the angiogenic
      phenotype as a net balance of positive and negative regulators of blood vessel
      growth. The extent to which the negative regulators are decreased during this
      switch may dictate whether a primary tumour grows rapidly or slowly and whether
      metastases grow at all.

PMID- 7584950
TI  - Immunophilins and the nervous system.
AB  - The search for immunosuppressant drugs to increase the success of organ
      transplantation led to the discovery of the immunophilins, proteins that
      interface with a range of signal transduction systems inside cells, especially in
      the nervous and immune systems. Here we review how these interesting molecules
      work and consider their therapeutic potential.

PMID- 7584952
TI  - The paternal inheritance of the centrosome, the cell's microtubule-organizing
      center, in humans, and the implications for infertility.
AB  - Successful fertilization in humans, achieved when parental chromosomes intermix
      at first mitosis, requires centrosome restoration and microtubule-mediated
      motility. Imaging of inseminated human oocytes reveals that the sperm introduces
      the centrosome. The centrosome then nucleates the new microtubule assembly to
      form the sperm aster--a step essential for successful fertilization. Oocytes from
      some infertile patients failed to complete fertilization because of defects in
      uniting the sperm and egg nuclei, indicating that failure to properly effect the
      cytoplasmic motions uniting the nuclei results in human infertility. These
      discoveries have important implications for infertility diagnosis and managing
      reproduction.

PMID- 7584951
TI  - Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with
      cystic fibrosis.
AB  - We report the results of a double-blind, placebo-controlled trial in nine cystic
      fibrosis (CF) subjects receiving cationic liposome complexed with a complementary
      DNA encoding the CF transmembrane conductance regulator (CFTR), and six CF
      subjects receiving only liposome to the nasal epithelium. No adverse clinical
      effects were seen and nasal biopsies showed no histological or immuno
      histological changes. A partial restoration of the deficit between CF and non-CF
      subjects of 20% was seen for the response to low Cl- perfusion following CFTR
      cDNA administration. This was maximal around day three and had reverted to
      pretreatment values by day seven. In some cases the response to low Cl- was
      within the range for non-CF subjects. Plasmid DNA and transgene-derived RNA were
      detected in the majority of treated subjects. Although these data are
      encouraging, it is likely that transfection efficiency and the duration of
      expression will need to be increased for therapeutic benefit.

PMID- 7584954
TI  - HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women.
AB  - A crucial requirement in the rational design of a prophylactic vaccine against
      the human immunodeficiency virus (HIV) is to establish whether or not protective
      immunity can occur following natural infection. The immune response to HIV
      infection is characterized by very vigorous HIV-specific cytotoxic T-lymphocyte
      (CTL) activity. We have identified four HIV-1 and HIV-2 cross-reactive peptide
      epitopes, presented to CTL from HIV-infected Gambians by HLA-B35 (the most common
      Gambian class I HLA molecule). These peptides were used to elicit HIV-specific
      CTLs from three out of six repeatedly exposed but HIV-seronegative female
      prostitutes with HLA-B35. These women remain seronegative with no evidence of HIV
      infection by polymerase chain reaction or viral culture. Their CTL activity may
      represent protective immunity against HIV infection.

PMID- 7584955
TI  - Microsatellite instability in primary neoplasms from HIV + patients.
AB  - AIDS is associated with a high risk of certain malignancies, notably Kaposi's
      sarcoma (KS) and B-cell non-Hodgkin's lymphoma (NHL). The pathogenesis of these
      malignancies is not fully understood. One mechanism of malignant transformation
      recently described in colon tumorigenesis results from defects in DNA mismatch
      repair, manifest as widespread microsatellite instability. We demonstrate a high
      rate of microsatellite instability in KS and aggressive lymphomas obtained from
      HIV-infected patients, whereas there is no evidence of instability in similar
      lesions from HIV-negative patients. Further elucidation of the underlying
      mechanisms responsible for HIV-associated instability in primary tumours may
      provide insight into the pathogenesis of these AIDS-related neoplasms.

PMID- 7584953
TI  - Basic fibroblast growth factor increases dopaminergic graft survival and function
      in a rat model of Parkinson's disease.
AB  - The clinical use of fetal neural grafts as an intracerebral source of dopamine
      for patients with Parkinson's disease has met with limited success. Since basic
      fibroblast growth factor (bFGF) enhances the survival and growth of dopaminergic
      neurons in vitro, we explored whether cells genetically modified to produce bFGF
      would improve the functional efficacy of dopaminergic neurons implanted into rats
      with experimental Parkinson's disease. Results show that bFGF-producing cells
      grafted together with fetal dopamine neurons have potent growth-promoting effects
      on the implanted neurons in vivo. Moreover, rats implanted with such co-grafts
      display the most pronounced behavioural improvements post-grafting. These
      findings not only provide insight into the function of bFGF in situ, but also
      suggest an approach for enhancing the survival and function of dopamine neurons
      grafted into the damaged brain.

PMID- 7584956
TI  - Serial magnetic resonance imaging of experimental atherosclerosis detects lesion
      fine structure, progression and complications in vivo.
AB  - A major problem in the study of lesions of atherosclerosis is the difficulty of
      imaging noninvasively the lesions and following their progression in vivo. To
      address this problem, we have developed advanced magnetic resonance techniques to
      noninvasively and serially image advanced lesions of atherosclerosis in the
      rabbit abdominal aorta. Both lumen and wall were imaged with high resolution.
      Progression of disease, resulting in increase in lesion mass, decrease in
      arterial lumen, or stenosis, and intralesion complications, can be detected.
      Images acquired in vivo correlate with the fine structure of the lesions of
      atherosclerosis, including the fibrous cap, necrotic core, and lesion fissures,
      as verified by gross examination, dissection microscopy, and histology. The
      ability to noninvasively identify the features of atherosclerotic plaques, has
      significant implications for determining risks and benefits associated with
      different therapeutic approaches.

PMID- 7584957
TI  - Making global blood safety a priority.

PMID- 7584958
TI  - The serum concentration of active transforming growth factor-beta is severely
      depressed in advanced atherosclerosis.
AB  - Recent evidence has led us to propose that transforming growth factor-beta (TGF
      beta) is a key inhibitor of atherosclerosis. We show here that a population of
      patients with advanced atherosclerosis all have less active TGF-beta in their
      sera than patients with normal coronary arteries, with a fivefold difference in
      average concentration between the two groups. This correlation with
      atherosclerosis is much stronger than for other known major risk factors and it
      may therefore have important diagnostic and prognostic significance. Aspirin
      medication correlates with an increase in active TGF-beta concentration,
      indicating that therapeutic interventions for TGF-beta are possible.

PMID- 7584961
TI  - Medical informatics in clinical medicine and the biosciences.

PMID- 7584960
TI  - Elimination of Ehrlich tumours by ATP-induced growth inhibition, glutathione
      depletion and X-rays.
AB  - ATP-induced tumour growth inhibition is accompanied by a selective decrease in
      the content of the tripeptide glutathione (GSH) within the cancer cells in vivo.
      Depletion of cellular GSH sensitizes tumours to chemotherapy and radiation, but
      the usefulness of this depletion depends on whether the levels of GSH can be
      reduced in the tumour relative to normal tissues. We report here that
      administration of ATP in combination with diethylmaleate and X-rays leads to
      complete regression of 95% of Ehrlich ascites tumours in mice. This shows that an
      aggressive tumour can be eliminated by using a therapy based on modulation of GSH
      levels in cancer cells.

PMID- 7584962
TI  - Illuminating informed consent.

PMID- 7584959
TI  - Purification and expansion of human Schwann cells in vitro.
AB  - The ability to culture cells from the human nervous system provides new insight
      into the pathophysiology of neurological diseases and could be crucial to the
      development of gene replacement therapies and neural transplantation. We report
      that the proliferation of human Schwann cells isolated from paediatric and adult
      nerves is sustained in vitro by recombinant glial growth factor. Agents that
      increase intracellular cyclic cAMP were also mitogenic towards Schwann cells but
      suppress growth of contaminating fibroblasts. As the lifespan of highly enriched
      cultures can be extended for up to twelve population doublings, large numbers of
      cells can be generated from nerve biopsies.

PMID- 7584963
TI  - The dangers of xenotransplantation.

PMID- 7584964
TI  - The cystic fibrosis heterozygote advantage.

PMID- 7584966
TI  - Animal rights and wrongs.

PMID- 7584965
TI  - Randomized clinical trials: the worst kind of epidemiology?

PMID- 7584967
TI  - The value of a family physician.

PMID- 7584969
TI  - Finnish mutations in Swedish HNPCC families.

PMID- 7584968
TI  - Enzymatic/non-enzymatic formation of nitric oxide.

PMID- 7584970
TI  - Managing medicine.

PMID- 7584971
TI  - gp 120: good, bad or indifferent?

PMID- 7584972
TI  - Courts favour HIV compensation.

PMID- 7584973
TI  - The state of the art in antisense research.

PMID- 7584975
TI  - The slowing of treatment discovery, 1965-1995.

PMID- 7584974
TI  - Does antisense exist?

PMID- 7584976
TI  - Whether and when an AIDS vaccine?

PMID- 7584977
TI  - No bones about fluoride.
AB  - We now have a number of effective drugs for osteoporosis. However, close
      inspection of clinical trials results suggests we should aim for even better
      ones.

PMID- 7584979
TI  - Subjective attacks on statistical significance.

PMID- 7584978
TI  - A sweeter life for diabetics?

PMID- 7584981
TI  - Human gene therapy--of tortoises and hares.

PMID- 7584980
TI  - The pros and cons of drug 'trafficking'.
AB  - Internalization of targeted therapeutics is often needed for efficacy, but also
      alters drug penetration of a tissue. A new model explores the trade-offs of
      intracellular drug trafficking.

PMID- 7584982
TI  - Palpometry: a novel concept in pain measurement.

PMID- 7584984
TI  - Gridlock: a model for coarctation of the aorta?

PMID- 7584983
TI  - Peptide vaccination against cancer?

PMID- 7584985
TI  - Gridlock, a localized heritable vascular patterning defect in the zebrafish.
AB  - We are using the zebrafish, Danio rerio, to identify genes that generate and
      pattern the vertebrate vasculature. We have isolated a recessive mutation,
      gridlockm145 (grlm145) in which blood flow to the tail is impeded by a localized
      vascular defect. Using a novel microangiographic method, we show that the
      blockade is in the anterior trunk, where the paired lateral dorsal aortae
      normally merge to form the single midline aorta. Arterial-venous shunts and
      collateral vessels develop in most mutant embryos, bypassing the lesion and
      reconstituting caudal blood flow. The grl defect resembles coarctation of the
      aorta, a human congenital cardiovascular malformation of unknown aetiology, in
      the location of the lesion and its consequences and in the mutants' dependence on
      collateral vessels for survival.

PMID- 7584986
TI  - A pilot study of ex vivo gene therapy for homozygous familial
      hypercholesterolaemia.
AB  - The outcome of the first pilot study of liver-directed gene therapy is reported
      here. Five patients with homozygous familial hypercholesterolaemia (FH) ranging
      in age from 7 to 41 years were enrolled; each patient tolerated the procedure
      well without significant complications. Transgene expression was detected in a
      limited number of hepatocytes of liver tissue harvested four months after gene
      transfer from all five patients. Significant and prolonged reductions in low
      density lipoprotein (LDL) cholesterol were demonstrated in three of five
      patients; in vivo LDL catabolism was increased 53% following gene therapy in a
      receptor negative patient, who realized a reduction in serum LDL equal to
      approximately 150 mg dl-1. This study demonstrates the feasibility of engrafting
      limited numbers of retrovirus-transduced hepatocytes without morbidity and
      achieving persistent gene expression lasting at least four months after gene
      therapy. The variable metabolic responses observed following low-level genetic
      reconstitution in the five patients studied precludes a broader application of
      liver-directed gene therapy without modifications that consistently effect
      substantially greater gene transfer.

PMID- 7584987
TI  - Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in
      obese and weight-reduced subjects.
AB  - Leptin, the gene product of the obese gene, may play an important role in
      regulating body weight by signalling the size of the adipose tissue mass. Plasma
      leptin was found to be highly correlated with body mass index (BMI) in rodents
      and in 87 lean and obese humans. In humans, there was variability in plasma
      leptin at each BMI suggesting that there are differences in its secretion rate
      from fat. Weight loss due to food restriction was associated with a decrease in
      plasma leptin in samples from mice and obese humans.

PMID- 7584988
TI  - Gene transfer through the blood-nerve barrier: NGF-engineered neuritogenic T
      lymphocytes attenuate experimental autoimmune neuritis.
AB  - Nerve-specific autoimmune T lymphocytes were used as vehicles to deliver
      therapeutically useful neurotrophic factors across the endothelial blood-nerve
      barrier. P2 protein-reactive T-lymphocyte lines from Lewis rats were transduced
      with a recombinant retrovirus containing the mouse nerve growth factor (NGF)
      gene. The engineered T cells released high amounts of NGF dependent on antigenic
      stimulation in vitro. After intravenous injection, the T cells infiltrated the
      rat peripheral nervous system and persisted there for at least two weeks. Local
      release of NGF from engineered T cells was demonstrable by immunocytochemistry
      and by an anti-inflammatory effect on infiltrating macrophages.

PMID- 7584989
TI  - Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in
      vaccinated macaques.
AB  - In order to develop a successful subunit vaccine against infection with the human
      immunodeficiency virus (HIV), protective immune effector functions must be
      identified. Until now, there has been only indirect evidence that HIV-specific
      cytotoxic T lymphocytes (CTLs) fulfill this role. Using the macaque simian
      immunodeficiency virus (SIV) model, the protective potential of nef-specific
      CTLs, stimulated by vaccination, was examined in animals challenged with a high
      intravenous dose of the pathogenic simian immunodeficiency virus,
      SIVmac251(32H)(pJ5). An inverse correlation was found between the vaccine-induced
      nef-specific CTL precursor frequency and virus load measured after challenge. In
      addition, the early decline in viraemia, observed in both vaccinated and
      unvaccinated control animals was associated with the development of virus
      specific CTL activity and not with the presence of virus-specific neutralizing
      antibodies. The results imply that vaccines that stimulate strong CTL responses
      could protect against HIV infection.

PMID- 7584990
TI  - Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model
      for HIV-associated neurotoxicity.
AB  - HIV infection can cause extensive neuronal loss and clinically a severe dementia.
      The cause of the neurotoxicity remains unclear as neurons are not infected, but
      disturbance of glutamate-linked calcium entry has been implicated. In this study,
      we have shown a decrease in HIV-infected brain of the expression of mRNA and
      protein of the GluR-A flop subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) glutamate receptor in cerebellar Purkinje cells. Although
      Purkinje cells are relatively resistant to loss, the observed disturbance of AMPA
      receptors may contribute to the neurotoxic process in other vulnerable brain
      regions and clinically to the development of dementia.

PMID- 7584991
TI  - Regression of established murine carcinoma metastases following vaccination with
      tumour-associated antigen peptides.
AB  - The cure of micrometastases following surgery is the major goal of cancer
      immunotherapy. We have recently isolated tumour-associated antigen (TAA)
      peptides, MUT 1 and MUT 2, derived from a mutated connexin 37 gap-junction
      protein, from the malignant 3LL-D122 murine lung carcinoma. We now report that
      synthetic MUT 1 or MUT 2 induces effective antitumour cytoxic T lymphocytes.
      Peptide vaccines protect mice from spontaneous metastases of 3LL-D122 tumours.
      Moreover, peptide vaccines reduce metastatic loads in mice carrying pre
      established micrometastases. Tumour-specific immunity was primarily mediated by
      CD8+ T cells. This is the first evidence that peptide therapy may be effective in
      treatment of residual tumours and provides a rationale for the development of
      peptide vaccines as a modality for cancer therapy.

PMID- 7584994
TI  - Plug and seal: prevention of hypoxic cardiocyte death by sealing membrane lesions
      with antimyosin-liposomes.
AB  - The hallmark of cell death is the development of cell membrane lesions. Such
      lesions in the myocardium are usually associated with acute myocardial
      infarction. Minimizing myocardial necrosis by thrombolytic reperfusion therapy
      constitutes the only major treatment to date. We envisioned a method to seal
      these membrane lesions using immunoliposomes as a novel adjunctive approach. An
      antigen to intracellular cytoskeletal myosin in hypoxic embryonic cardiocytes is
      used as an anchoring site, and a specific antibody on immunoliposomes as the
      anchor to plug and to seal the membrane lesions. H9C2 cells were used because
      they are cardiocytes and are propagated in tissue culture and their viability may
      be assessed by various methods. Viability assessed by [3H]thymidine uptake in
      hypoxic cardiocyte cultures (n = 6 each) treated with antimyosin-immunoliposomes
      (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to that of normoxic cells (3.68 +/-
      0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells
      (0.115 +/- 0.155 x 10(6) c.p.m.) or hypoxic cells treated with plain liposomes
      (1.140 +/- 0.577 x 10(6) c.p.m.). These results were reconfirmed by trypan blue
      exclusion and by fluorescent, confocal and transmission electron microscopy. They
      indicated that cell death in hypoxic cardiocytes can be prevented by targeted
      cell membrane sealing. This concept of cell salvage should be applicable in the
      prevention of cell death in different biological systems.

PMID- 7584992
TI  - Induction of dopaminergic neuron phenotype in the midbrain by Sonic hedgehog
      protein.
AB  - Loss of substantia nigra dopaminergic neurons, which develop from the ventral
      region of the midbrain, is associated with Parkinson's disease. During
      embryogenesis, induction of these and other ventral neurons is influenced by
      interactions with the induction of mesoderm of the notochord and the floor plate,
      which lies at the ventral midline of the developing CNS. Sonic hedgehog encodes a
      secreted peptide, which is expressed in notochord and floor plate cells and can
      induce appropriate ventral cell types in the basal forebrain and spinal cord.
      Here we demonstrate that Sonic hedgehog is sufficient to induce dopaminergic and
      other neuronal phenotypes in chick mesencephalic explants in vitro. We find that
      Sonic hedgehog is a general ventralizing signal in the CNS, the specific response
      being determined by the receiving cells. These results suggest that Sonic
      hedgehog may have utility in the induction of clinically important cell types.

PMID- 7584993
TI  - Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit
      remarkable axonal target specificity and distinct growth patterns of glial and
      axonal fibres.
AB  - Clinical trials are under way using fetal cells to repair damaged neuronal
      circuitry. However, little is known about how transplanted immature neurons can
      grow anatomically correct connections in the adult central nervous system (CNS).
      We transplanted embryonic porcine neural cells in vivo into adult rat brains with
      neuronal and axonal loss typical of Parkinson's or Huntington's disease. Using
      complementary species-specific cellular markers, we found donor axons and CD44+
      astroglial fibres in host white matter tracts up to 8 mm from CNS transplant
      sites, although only donor axons were capable of reaching correct gray matter
      target regions. This work demonstrates that adult host brain can orient growth of
      transplanted neurons and that there are differences in transplant donor glial and
      axonal growth patterns in cellular repair of the mature CNS.

PMID- 7584995
TI  - Measurement of glucose in diabetic subjects using noninvasive transdermal
      extraction.
AB  - Results from the Diabetes Care and Complications Trial show that tight blood
      glucose control significantly reduces the long-term complications of diabetes
      mellitus. In that study, frequent self-testing of glucose and insulin
      administration resulted in a significant reduction in long-term complications.
      This protocol, however, also resulted in a threefold increase in the frequency of
      hypoglycaemic incidents. Currently, self-testing requires a drop of blood for
      each measurement. The pain and inconvenience of self-testing, along with the fear
      and danger of hypoglycaemia has led to poor patient acceptance of a tight control
      regimen, despite the clear long-term advantages. A continuously worn, noninvasive
      method to periodically measure glucose would provide a convenient and comfortable
      means of frequent self-testing. A continuously worn device could also alert the
      user of low glucose levels, thereby reducing the incidence of hypoglycaemia. Guy
      et al. demonstrated a noninvasive method to transport glucose through the skin
      using low-level electrical current. To provide a quantitative measurement, the
      flux of glucose extracted across the skin must correlate with serum glucose in a
      predictive manner. The results presented here show a quantitative relationship
      between serum and transdermally extracted glucose in diabetics.

PMID- 7584996
TI  - In utero gene transfer into the pulmonary epithelium.
AB  - In early gestation the internal surface of the lung is structurally simple and an
      ideal target for somatic gene transfer. The transfer of genes into the growing
      lung would be particularly useful in the prenatal correction of cystic fibrosis,
      which has devastating pulmonary complications. In addition, in utero gene therapy
      has the potential to immunotolerize the individual, and thereby to avoid the
      immune reactions now seen with the current generation of adenoviral vectors. We
      injected a replication-defective adenoviral vector containing the lacZ reporter
      gene (Ad5.CMVlacZ) into the amniotic fluid of rat pups on the 16th day of
      gestation. At 16 days of gestation, rat lungs are equivalent in maturity to those
      of a 22-week human fetus as their airways are lined with undifferentiated
      multipotential stem cells. The pups showed high-level reporter gene expression in
      their airways a week following birth (13 days following infection). The
      expression was maintained during a time when the lung volume increased
      approximately 20-fold, alveolarization occurred, and the epithelial cells
      differentiated. These data establish gene targeting of undifferentiated fetal
      cells as an effective means of gene therapy.

PMID- 7584997
TI  - Founding mutations and Alu-mediated recombination in hereditary colon cancer.
AB  - By screening members of Finnish families displaying hereditary nonpolyposis
      colorectal cancer (HNPCC) for predisposing germline mutations in MSH2 and MLH1,
      we show that two mutations in MLH1 together account for 63% (19/30) of kindreds
      meeting international diagnostic criteria. Mutation 1, originally detected as a
      165-base pair deletion in MLH1 cDNA comprising exon 16, was shown to consist of a
      3.5-kilobase genomic deletion most likely resulting from Alu-mediated
      recombination. Mutation 2 destroys the splice acceptor site of exon 6. A simple
      diagnostic test based on polymerase chain reaction was designed for both
      mutations. Our results show that these two ancestral founding mutations account
      for a majority of Finnish HNPCC kindreds and represent the first report of Alu
      mediated recombination causing a prevalent, dominantly inherited predisposition
      to cancer.

PMID- 7585000
TI  - Japan to open first AIDS clinic.

PMID- 7584998
TI  - Blood substitutes--a moving target.

PMID- 7584999
TI  - Radiotherapy for genes that cause cancer.
AB  - Many approaches to cancer gene radiotherapy are possible. Even existing
      strategies, devised with other goals in mind, can cause radiosensitization by
      altering the intrinsic radiosensitivity of tumour cells or by modifying the
      tumour microenvironment. Small increases in the levels of radiosensitization
      could, over a fractionated radiation course, have major effects on the
      probability of tumour cure. The clinical application of gene radiotherapy will
      require use of in vivo gene delivery systems that still need validation but,
      because radiation is effective at decreasing tumour burden, genes will not have
      to be expressed in all cells in order to achieve a cure.

PMID- 7585001
TI  - Witches, multiple personalities, and other psychiatric artifacts.
AB  - Contemporary psychiatric misdirections derived primarily from standard medical
      errors of oversimplification, misplaced emphasis, and invention are reviewed.
      These particular errors, however, were in part prompted and sustained by the
      sociocultural fads and fashions of the day. The results have been disastrous for
      everyone--patients, families, the public and psychiatry itself.

PMID- 7585003
TI  - Tumour dormancy: not so sleepy after all.

PMID- 7585002
TI  - Academic misconduct.

PMID- 7585005
TI  - Sand in the sheets.

PMID- 7585004
TI  - Apoptosis in HIV infection.

PMID- 7585006
TI  - A fight to the death.

PMID- 7585007
TI  - Is the spinal muscular atrophy gene found?

PMID- 7585008
TI  - Apoptosis occurs predominantly in bystander cells and not in productively
      infected cells of HIV- and SIV-infected lymph nodes.
AB  - Although 13 years have passed since identification of human immunodeficiency
      virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its
      primary target, the T cell that carries the CD4 antigen. We and others have shown
      an increase in the percentage of apoptotic cells among circulating CD4+ (and
      CD8+) T cells of HIV-seropositive individuals and an increase in frequency of
      apoptosis with disease progression. However, it is not known if this apoptosis
      occurs in infected or uninfected T cells. We show here, using in situ labelling
      of lymph nodes from HIV-infected children and SIV-infected macaques, that
      apoptosis occurs predominantly in bystander cells and not in the productively
      infected cells themselves. These data have implications for pathogenesis and
      therapy, namely, arguing that rational drug therapy may involve combination
      agents targeting viral replication in infected cells and apoptosis of uninfected
      cells.

PMID- 7585009
TI  - Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta
      protein following head injury.
AB  - Deposition of amyloid beta-protein (A beta) in the brain plays a key role in the
      pathogenesis of Alzheimer's disease. Apolipoprotein E epsilon 4 allele (apo E
      epsilon 4) is a strong risk factor for Alzheimer's disease, and there is in vitro
      evidence that apo E is directly involved in A beta deposition. Head injury is an
      epidemiological risk factor for Alzheimer's disease and deposition of A beta
      occurs in approximately one-third of individuals dying after a severe head
      injury. We report here that the frequency of apo E-epsilon 4 in those individuals
      with A beta deposition following head injury (0.52) is higher than in most
      studies of Alzheimer's disease, while in those head-injured individuals without A
      beta deposition the apo E-epsilon 4 frequency (0.16) is similar to controls
      without Alzheimer's disease (P < 0.00001). This finding provides further evidence
      linking apo E-epsilon 4 with A beta deposition in vivo and suggests that known
      environmental and genetic risk factors for Alzheimer's disease may act
      additively. In addition our finding indicates a genetic susceptibility to the
      effects of a head injury.

PMID- 7585010
TI  - In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid
      beta-peptide analogues.
AB  - We have studied the effects of amyloid beta-peptide analogues on the activity of
      tissue-type plasminogen activator (t-PA) in vitro. We have found that these
      peptides have a marked stimulatory effect upon plasminogen activation by t-PA,
      comparable to that of known stimulators of t-PA. This stimulatory activity
      appears to increase when beta-peptides form aggregated fibrillar structures
      similar to those found in amyloid deposits. This finding is significant in that
      it may provide insights into the pathogenesis of hereditary cerebral haemorrhage
      with amyloidosis-Dutch type (HCHWA-D) and cerebral amyloid angiopathy-related
      cerebral haemorrhage. It may also provide an explanation for the deaths resulting
      from intracerebral haemorrhage that have occurred in patients undergoing t-PA
      treatment for acute myocardial infarction.

PMID- 7585011
TI  - Arresting amyloidosis in vivo using small-molecule anionic sulphonates or
      sulphates: implications for Alzheimer's disease.
AB  - Amyloid is a term for extracellular protein fibril deposits that have
      characteristic tinctorial and structural properties. Heparan sulphate, or the
      heparan sulphate proteoglycan perlecan, has been identified in all amyloids and
      implicated in the earliest stages of inflammation-associated (AA) amyloid
      induction. Heparan sulphate interacts with the AA amyloid precursor and the beta
      peptide of Alzheimer's amyloid, imparting characteristic secondary and tertiary
      amyloid structural features. These observations suggest that molecules that
      interfere with this interaction may prevent or arrest amyloidogenesis. We
      synthesized low-molecular-weight (135-1,000) anionic sulphonate or sulphate
      compounds. When administered orally, these compounds substantially reduced murine
      splenic AA amyloid progression. They also interfered with heparan sulphate
      stimulated beta-peptide fibril aggregation in vitro.

PMID- 7585012
TI  - Dormancy of micrometastases: balanced proliferation and apoptosis in the presence
      of angiogenesis suppression.
AB  - In cancer patients, dormant micrometastases are often asymptomatic and clinically
      undetectable, for months or years, until relapse. We have studied dormant lung
      metastases under angiogenesis suppression in mice. The metastases exhibited rapid
      growth when the inhibition of angiogenesis was removed. Tumour cell
      proliferation, as measured by bromodeoxyuridine incorporation and
      immunohistochemical staining proliferating cell nuclear antigen, was not
      significantly different in dormant and growing metastases. However, tumour cells
      of dormant metastases exhibited a more than threefold higher incidence of
      apoptosis. These data show that metastases remain dormant when tumour cell
      proliferation is balanced by an equivalent rate of cell death and suggest that
      angiogenesis inhibitors control metastatic growth by indirectly increasing
      apoptosis in tumour cells.

PMID- 7585013
TI  - Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic
      phospholipids: insight into the mechanism and reversal of NSAID-induced
      gastrointestinal injury.
AB  - The molecular basis of the injurious actions of non-steroidal anti-inflammatory
      drugs (NSAIDs) on the gastrointestinal (GI) tract is only partly understood. In
      this study we have obtained evidence, employing both in vitro and in vivo
      systems, that five NSAIDs have the ability to form a chemical association with
      zwitterionic phospholipids. Since this same class of phospholipids line the
      luminal aspects of the mucus gel layer to provide it with non-wettable
      properties, this intermolecular association may be the mechanism by which NSAIDs
      attenuate the hydrophobic barrier properties of the upper GI tract.
      Preassociating a number of NSAIDs with exogenous zwitterionic phospholipids
      prevented this increase in surface wettability of the mucus gel layer and
      protected rats against the injurious GI side-effects of these drugs, while
      enhancing their lipid permeability, antipyretic and anti-inflammatory activity.

PMID- 7585014
TI  - Neurodevelopmental effects of the FMR-1 full mutation in humans.
AB  - Brain dysfunction is the most important sequelae of the fragile X (FMR-1)
      mutation, the most common heritable cause of developmental disability. Using
      magnetic resonance imaging (MRI) and quantitative morphometry, we have compared
      the neuroanatomy of 51 individuals with an FMR-1 mutation with matched controls
      and showed that subjects with an FMR-1 mutation have increased volume of the
      caudate nucleus and, in males, the lateral ventricle. Both caudate and lateral
      ventricular volumes are correlated with IQ. Caudate volume is also correlated
      with the methylation status of the FMR-1 gene. Neuroanatomical differences
      between two monozygotic twins with an FMR-1 mutation who are discordant for
      mental retardation are localized to the cerebellum, lateral ventricles and
      subcortical nuclei. These findings suggest that the FMR-1 mutation causing the
      fragile X syndrome leads to observable changes in neuroanatomy that may be
      relevant to the neurodevelopmental disability and behavioural problems observed
      in affected individuals.

PMID- 7585015
TI  - Regional changes of ciliary neurotrophic factor and nerve growth factor levels in
      post mortem spinal cord and cerebral cortex from patients with motor disease.
AB  - Ciliary neurotrophic factor (CNTF) rescues motor neurons in animal models of
      injury and neurodegeneration, and disruption of the mouse CNTF gene results in
      motor neuron degeneration in mature adults. Glial cells increase nerve growth
      factor (NGF) expression in neuropathological conditions, and the sensory system
      can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic
      disease. We therefore studied CNTF and NGF levels in post mortem spinal cord and
      cerebral cortex from patients with ALS and matched controls. We report a marked
      decrease of CNTF in the ventral horn of spinal cord in ALS, with no change in
      cerebral motor cortex. In contrast, NGF levels were decreased in ALS cerebral
      motor cortex, where the corticospinal tract originates, but increased in the
      lateral column of spinal cord, which includes the region of corticospinal tract
      degeneration in ALS. Both CNTF and NGF levels were decreased in ALS dorsal spinal
      cord.

PMID- 7585016
TI  - Exploring the universe of molecules for new drugs.

PMID- 7585017
TI  - A conundrum of ethics.

PMID- 7585020
TI  - Politics and genes.

PMID- 7585018
TI  - Carotenoids protect against cell membrane damage by the nitrogen dioxide radical.

PMID- 7585019
TI  - The impact of family history on early detection of prostate cancer.

PMID- 7585021
TI  - Gene therapy for cystic fibrosis.

PMID- 7585024
TI  - Dingell disavows 'Dingell' report on Gallo.

PMID- 7585023
TI  - Premature ischaemic heart disease and the gene for coagulation factor V.

PMID- 7585022
TI  - IL-6 release and airway administration of human CFR cDNA adenovirus vector.

PMID- 7585025
TI  - FDA panel reluctantly approves AIDS vaccine trial.

PMID- 7585027
TI  - In defence of indirect costs.
AB  - In all nations that do science, researchers need support not only for the direct
      costs of experimentation, but also for the direct costs of their institutions.
      The US is about to see a vast change in the system for such costs that will
      affect its ability to do science and, quite possibly, limit the opportunities for
      researchers from other countries who are studying or working in US laboratories.

PMID- 7585026
TI  - DNA-based testing not yet ready for routine screening of blood.

PMID- 7585028
TI  - The minor issue of electroconvulsive therapy.
AB  - ECT can be life-saving for patients with certain mental illnesses, such as severe
      depression, but that is no reason to allow ECT without informed consent. Nor is
      there general medical justification for the use of ECT on children, a practice in
      the United Kingdom that is out of control.

PMID- 7585030
TI  - Do the ends justify the means?

PMID- 7585029
TI  - Radical directions in Parkinson's disease.

PMID- 7585031
TI  - A peppy response to PEPI results.

PMID- 7585032
TI  - Agalactosyl IgG and mannose-binding proteins: biochemical nicety or
      pathophysiological paradigm?

PMID- 7585033
TI  - Does Borna disease virus infect humans?

PMID- 7585034
TI  - Getting to the core of the matter.

PMID- 7585035
TI  - Multiple sclerosis: TNF revisited, with promise.

PMID- 7585036
TI  - A miracle enough: the power of mice.
AB  - "A mouse is miracle enough to stagger sextillions of infidels" Leaves of Grass,
      Walt Whitman The mouse has become our experimental surrogate. It is the creature
      we turn to to do the experiments, so important in reaching an understanding of
      ourselves, that are either technically impossible or morally inconceivable in
      human subjects.

PMID- 7585037
TI  - Selective liver targeting of antivirals by recombinant chylomicrons--a new
      therapeutic approach to hepatitis B.
AB  - Hepatitis B virus (HBV) infection is the world's most important chronic virus
      infection. No safe and effective treatment is available at present, and clinical
      exploration of promising antiviral agents, such as nucleoside analogues is
      hampered because of significant side-effects due to their aspecific body
      distribution. We are exploring the possibility of the selective delivery of
      antiviral active drugs to liver parenchymal cells, the main site of infection and
      replication of HBV. Chylomicrons, which transport dietary lipids into the liver
      via apolipoprotein E-specific receptors, could serve as drug carriers. However,
      their endogenous nature hampers their application as pharmaceutical drug
      carriers. We report here that incorporation of a derivative of the nucleoside
      analogue iododeoxyuridine into recombinant chylomicrons leads to selective
      targeting to liver parenchymal cells. Potentially effective intracellular drug
      concentrations of 700 nM can be achieved, and we therefore anticipate that these
      drug carrier complexes represent a conceptual advance in the development of an
      effective and safe therapy for hepatitis B.

PMID- 7585038
TI  - Overexpressing Cu/Zn superoxide dismutase enhances survival of transplanted
      neurons in a rat model of Parkinson's disease.
AB  - A high survival rate of grafted dopamine neurons is crucial for reversing
      neurological deficits following brain tissue transplantation in Parkinson's
      disease. For unknown reasons the survival rate of transplanted dopamine neurons
      is only around 10% in experimental animals. The hypothesis that oxidative stress
      causes the loss of transplanted neurons was tested by grafting neurons from
      transgenic mice that overexpress Cu/Zn superoxide dismutase. Compared with the
      survival of those taken from non-transgenic littermates, the survival was 4 times
      higher for the transgenic dopamine neurons with a concomitant more extensive
      functional recovery. The results provide direct support for the free radical
      hypothesis of dopaminergic neuron death in brain tissue grafting.

PMID- 7585039
TI  - Borna disease virus genome transcribed and expressed in psychiatric patients.
AB  - Borna disease virus (BDV) is a neurotropic, negative and single-stranded
      enveloped RNA virus that persistently infects various domestic animal species.
      Infection causes disturbances in behaviour and cognitive functions, but can also
      lead to a fatal neurologic disease. Human infections seemed likely, since serum
      antibodies were detected in neuropsychiatric patients. Further proof came from
      our discovery that peripheral blood monocytes carry viral antigens. Here, we
      present the first data on different viral genomic transcripts in such patients'
      cells as well as sequence data of transcripts. Both viral markers seem to
      coincide with acute episodes of mood disorders, thus pointing to a new human
      virus infection possibly threatening mental health.

PMID- 7585040
TI  - Glycosylation changes of IgG associated with rheumatoid arthritis can activate
      complement via the mannose-binding protein.
AB  - The glycosylation of the circulating immunoglobulin-gamma (IgG) antibody
      molecules changes in rheumatoid arthritis. The extent of the changes correlates
      with the disease severity and reverses in remission. We demonstrate here that the
      alteration in glycosylation associated with rheumatoid arthritis can create a new
      mode for the interaction of IgG with complement through binding to the
      collagenous lectin mannose-binding protein (MBP). Rheumatoid arthritis is
      associated with a marked increases in IgG glycoforms that lack galactose
      (referred to as G0 glycoforms) in the Fc region of the molecule and that
      terminate in N-acetyl glucosamine (GlcNAc). We show, using nuclear magnetic
      resonance (NMR) and X-ray data, that these terminal GlcNAc residues become
      accessible for MBP binding. We further demonstrate that multiple presentation of
      IgG-G0 glycoforms to MBP results in activation of the complement. This suggests
      that a contribution to the chronic inflammation of the synovial membrane could
      arise from the localization of the IgG-G0 glycoforms in the affected joint and
      from resulting activation of complement.

PMID- 7585041
TI  - The antidepressant rolipram suppresses cytokine production and prevents
      autoimmune encephalomyelitis.
AB  - In multiple sclerosis (MS) and its animal model experimental autoimmune
      encephalomyelitis (EAE) the cytokines tumour necrosis factor-alpha (TNF),
      lymphotoxin-alpha (LT), and interferon-gamma (IFN-gamma) are of central
      pathogenetic importance. A therapy capable of stopping neurological deterioration
      in MS patients is not yet available. Here, we report that rolipram, a selective
      type IV phosphodiesterase inhibitor, stereospecifically suppresses the production
      of TNF/LT and less strongly also IFN-gamma in human and rat auto-reactive T
      cells. Moreover, we show that rolipram is an effective treatment for EAE.
      Rolipram has extensively been studied in humans for the treatment of depression,
      but has not yet been marketed. The data presented here identify rolipram as
      potential therapy for multiple sclerosis and provoke the immediate initiation of
      clinical trials.

PMID- 7585042
TI  - Correlating telomerase activity levels with human neuroblastoma outcomes.
AB  - Telomerase activity was analysed in 100 neuroblastoma cases. Although telomerase
      activity was not detected in normal adrenal tissues or benign ganglioneuromas,
      almost all neuroblastomas (94%) did express it, suggesting an important role for
      telomerase in neuroblastoma development. Neuroblastomas with high telomerase
      activity had other genetic changes (for example, N-myc amplification) and an
      unfavourable prognosis, whereas tumours with low telomerase activity were devoid
      of such genetic alterations and were associated with a favourable prognosis.
      Three neuroblastomas lacking telomerase activity regressed (stage IVS). Thus
      telomerase expression may be required as a critical step in the multigenetic
      process of tumorigenesis, and two different pathways may exist for the
      development of neuroblastoma.

PMID- 7585043
TI  - Antifibrinolytic activity of apolipoprotein(a) in vivo: human apolipoprotein(a)
      transgenic mice are resistant to tissue plasminogen activator-mediated
      thrombolysis.
AB  - The extensive homology between apolipoprotein(a) and plasminogen has led to the
      hypothesis that the increased risk for atherosclerosis, cardiac disease and
      stroke associated with elevated levels of apolipoprotein(a) may reflect
      modulation of fibrinolysis. We have investigated the role of apolipoprotein(a) on
      clot lysis in transgenic mice expressing the human apolipoprotein(a) gene. These
      mice develop fatty streak lesions resembling early lesions of human
      atherosclerosis. Pulmonary emboli were generated in mice by injection, through
      the right jugular vein, of a human platelet-rich plasma clot radiolabelled with
      technetium-99m-labelled antifibrin antibodies. Tissue plasminogen activator was
      introduced continuously via the right jugular vein. Clot lysis, determined by ex
      vivo imaging, was depressed in mice carrying the apolipoprotein(a) transgene
      relative to their sex-matched normal littermates. These results directly
      demonstrate an in vivo effect of apolipoprotein(a) on fibrinolysis, an effect
      that may contribute to the pathology associated with elevated levels of this
      protein.

PMID- 7585045
TI  - Induction of human autologous cytotoxic T lymphocytes on formalin-fixed and
      paraffin-embedded tumour sections.
AB  - Human autologous tumour-specific cytotoxic T lymphocytes (CTL) were generated
      from peripheral blood on small formalin-fixed paraffin-embedded sections of a
      gastric cancer. The CTL killed live target cells at an effector/target ratio of 1
      within 24 hours and showed the same target specificity as those induced on live
      cancer cells. The killing activity of the CTL lasted for more than four months in
      culture and was inhibited by antibodies against CD8 and MHC-class I. These
      results suggest that adoptive immunotherapy of tumours will be possible with CTL
      induced on a stable source of tumour antigen.

PMID- 7585046
TI  - Pseudotyped retroviral vectors for studies of human gene therapy.

PMID- 7585044
TI  - Rotenoids mediate potent cancer chemopreventive activity through transcriptional
      regulation of ornithine decarboxylase.
AB  - For the discovery of new cancer chemopreventive agents, we have studied the
      potential of plant extracts to inhibit phorbol ester-induced ornithine
      decarboxylase (ODC) activity in cell culture. Four active rotenoids were obtained
      from the African plant Mundulea sericea (Leguminosae). These isolates were highly
      potent when evaluated for inhibition of chemically induced preneoplastic lesions
      in mammary organ culture and inhibition of papillomas in the two-stage mouse skin
      model, and they appear to function by a unique mechanism at the level of ODC
      messenger RNA expression. Based on our findings, rotenoids can be regarded as
      promising new chemopreventive or anticancer agents.

PMID- 7585047
TI  - Ribozymes in gene therapy.

PMID- 7585048
TI  - Clinical investigation: an endangered science.

PMID- 7585049
TI  - Elevated plasma levels of TGF-beta 1 in patients with invasive prostate cancer.

PMID- 7585050
TI  - Coxsackie virus and diabetes revisited.

PMID- 7585051
TI  - AIDS drugs lurch towards market.

PMID- 7585052
TI  - Assessing animal models of AIDS.

PMID- 7585053
TI  - Anatomical research lives!

PMID- 7585054
TI  - Genetics and environment in Hodgkin's disease.

PMID- 7585055
TI  - Molecular DIY with hairpins and hammerheads.

PMID- 7585056
TI  - Testing for cancer genes: decisions, decisions.

PMID- 7585057
TI  - CTL to HIV-1: surrogates or sirens.

PMID- 7585058
TI  - Filling in the matrix of kidney disease.

PMID- 7585059
TI  - Sickle cell paths converge on hydroxyurea.

PMID- 7585060
TI  - Molecular foundations of cancer: new targets for intervention.
AB  - Conceptual and practical advances in molecular medicine are changing our
      understanding of cancer pathogenesis. In time this should provide the opportunity
      to alter the natural history of many cancers.

PMID- 7585061
TI  - HIV-1 recombinant poxvirus vaccine induces cross-protection against HIV-2
      challenge in rhesus macaques.
AB  - Rhesus macaques were immunized with attenuated vaccinia or canarypox human
      immunodeficiency virus type 1 (HIV-1) recombinants and boosted with HIV-1 protein
      subunits formulated in alum. Following challenge with HIV-2SBL6669, three out of
      eight immunized macaques resisted infection for six months and another exhibited
      significantly delayed infection, whereas all three naive controls became
      infected. Immunizations elicited both humoral and cellular immune responses;
      however, no clear correlates of protection were discerned. Although more
      extensive studies are now called for, this first demonstration of cross
      protection between HIV-1 and -2 suggests that viral variability may not be an
      insurmountable problem in the design of a global AIDS vaccine.

PMID- 7585063
TI  - Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1
      allele.
AB  - Various types of alcoholics have been described and heredity has been shown to be
      involved in some of these types. An important role of the mesolimbic dopamine
      system has been suggested in the reinforcing effects of alcohol and recent
      molecular genetic studies are implicating the gene for the D2 dopamine receptor
      (DRD2) in alcoholism. In a double-blind study, bromocriptine, a DRD2 agonist, or
      placebo was administered to alcoholics with either the A1 (A1/A1 and A1/A2
      genotypes) or only the A2 (A2/A2 genotype) allele of the DRD2 gene. The greatest
      improvement in craving and anxiety occurred in the bromocriptine-treated A1
      alcoholics and attrition was highest in the placebo-treated A1 alcoholics. The
      feasibility of a pharmacogenetic approach in treating certain types of alcoholics
      is suggested.

PMID- 7585062
TI  - Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to
      selection for mutant HIV variants and subsequent disease progression.
AB  - An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic
      T lymphocyte (CTL) clone directed against the HIV-1 nef protein. This clone was
      adoptively transferred to determine whether supplementing CTL activity could
      reduce viral load or improve clinical course. Unexpectedly, infusion was followed
      by a decline in circulating CD4+ T cells and a rise in viral load. Some of the
      HIV isolates obtained from the plasma or CD4+ cells of the patient were lacking
      the nef epitope. These results suggest that active CTL selection of viral
      variants could contribute to the pathogenesis of AIDS and that clinical
      progression can occur despite high levels of circulating HIV-1-specific CTLs.

PMID- 7585064
TI  - In utero surgery rescues neurological function at birth in sheep with spina
      bifida.
AB  - We hypothesize that the neurologic deficit associated with open spina bifida is
      not directly caused by the primary defect but rather is due to chronic mechanical
      and chemical trauma since the unprotected neural tissue is exposed to the
      intrauterine environment. We report here that exposure of the normal spinal cord
      to the amniotic cavity in midgestational sheep fetuses leads to a human-like open
      spina bifida with paraplegia at birth, indicating that the exposed neural tissue
      is progressively destroyed during pregnancy. When open spina bifida was repaired
      in utero at an intermediate stage, the animals had near-normal neurologic
      function. The spinal cord was deformed but largely preserved. These findings
      suggest that secondary neural tissue destruction during pregnancy is primarily
      responsible for the functional loss and that timely in utero repair of open spina
      bifida might rescue neurologic function.

PMID- 7585065
TI  - Genetic instability occurs in the majority of young patients with colorectal
      cancer.
AB  - Replication errors (RER) associated with genetic instability have been found in
      cancers of several different types and particularly in the tumours of patients
      with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined
      the prevalence of such instability in relation to age among patients without
      HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or
      younger exhibited instability (58% of 31 patients), whereas CRCs from patients
      older than 35 uncommonly did (12% of 158, p < 0.0001). Twelve of the patients
      under 35 with instability were evaluated for alterations of mismatch repair
      genes, and five were found to harbour germline mutations. These data suggest that
      the mechanisms underlying tumour development in young CRC patients differ from
      those in most older patients, regardless of HNPCC status. The results have
      important implications for genetic testing and management of young CRC patients
      and their families.

PMID- 7585066
TI  - Long-term delivery of a lysosomal enzyme by genetically modified fibroblasts in
      dogs.
AB  - We have evaluated the feasibility and efficacy of intraperitoneal implants (neo
      organs) for protein delivery in large animals. Skin biopsies were taken from four
      healthy dogs. Primary fibroblast cultures were transduced with a retroviral
      vector coding for the human beta-glucuronidase. One to six lattices each
      containing 10(9) skin fibroblasts were implanted into the omentum of the donor
      animal. Laparotomies performed at regular intervals showed vascularized neo
      organs without local inflammation. Human beta-glucuronidase levels equivalent to
      0.8 to 3.1% of the endogenous canine activity were detected for up to 340 days on
      liver biopsy samples. These results indicate that neo-organs can be considered
      for the long-term delivery of therapeutic proteins or enzymes in humans.

PMID- 7585067
TI  - The PKD1 gene produces a developmentally regulated protein in mesenchyme and
      vasculature.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      human genetic diseases. In addition to polycystic kidneys, the disease can cause
      cystic changes in liver and other organs, cardiac valvular insufficiency and
      cerebral arterial aneurysms. Using antibodies raised against the predicted gene
      product of PKD1, which is mutated in about 85% of ADPKD cases, we show that PKD1
      is a 530-kD protein localized to the extracellular matrix of kidney, liver and
      cerebral blood vessels. We discovered that the PKD1 protein was highly expressed
      in the mesenchyme of developing kidney and liver, transiently localized in the
      developing glomerulus and juxtaglomerular apparatus and restricted to
      perivascular, extraglomerular areas in adult renal cortex. These data suggest
      that the PKD1 protein plays a role in renal and hepatic morphogenesis.

PMID- 7585068
TI  - Tau protein directly interacts with the amyloid beta-protein precursor:
      implications for Alzheimer's disease.
AB  - The simultaneous presence of intracellular neurofibrillary tangles (NFT) and
      extracellular senile plaques in Alzheimer's disease (AD) suggests that the two
      lesions could be synergistically interrelated. However, although the main protein
      components of NFT and senile plaques, tau (tau) and amyloid beta-protein,
      respectively, are well characterized, the molecular mechanisms responsible for
      their deposition in lesions are unknown. We demonstrate, using four independent
      techniques, that tau directly interacts with a conformation-dependent domain of
      the amyloid beta-protein precursor (beta PP) encompassing residues beta PP714
      723. The putative tau-binding domain includes beta PP717 mutation sites that are
      associated with familial forms of AD. Our findings strongly suggest that NFT and
      senile plaques, often thought of as independent structures, may play a role in
      each other's formation during the pathogenesis of AD.

PMID- 7585069
TI  - High nitric oxide production in human paranasal sinuses.
AB  - Nitric oxide (NO) is present in air derived from the nasal airways. However, the
      precise origin and physiological role of airway-derived NO are unknown. We report
      that NO in humans is produced by epithelial cells in the paranasal sinuses and is
      present in sinus air in very high concentrations, close to the highest
      permissible atmospheric pollution levels. In immunohistochemical and mRNA in situ
      hybridization studies we show that an NO synthase most closely resembling the
      inducible isoform is constitutively expressed apically in sinus epithelium. In
      contrast, only weak NO synthase activity was found in the epithelium of the nasal
      cavity. Our findings, together with the well-known bacteriostatic effects of NO,
      suggest a role for NO in the maintenance of sterility in the human paranasal
      sinuses.

PMID- 7585071
TI  - Functional magnetic resonance imaging depicts the brain in action.
AB  - In summary, FMRI is a new technique for discovering the organization and function
      of the brain. The ability rapidly and non-invasively to image regional cerebral
      blood flow, blood volume, and blood oxygenation may strengthen diagnoses in
      neurology, neurosurgery, and trauma medicine. The ability to localize specific
      functions in an individual's brain will have a large impact on the planning of
      therapeutic interventions, and in predicting outcomes after disease and injury.
      Substantial contributions to the diagnosis and treatment of psychiatric disorders
      are expected based on the ability to image subtle differences in a patient's
      response to auditory and visual stimuli of different emotional content.

PMID- 7585070
TI  - Association of hepatitis B surface antigen carriage with severe malaria in
      Gambian children.
AB  - Severe malaria is a major cause of childhood mortality in sub-Saharan Africa but
      the factors predisposing children to severe forms of malaria have not been fully
      elucidated. In a case-control study of over 1,200 Gambian children hepatitis B
      virus carriage was significantly increased amongst cases of severe malaria
      compared to matched controls. We suggest that this association may relate to
      impaired clearance of liver stage parasites in the presence of the reduced level
      of HLA class I antigen expression on hepatocytes infected by hepatitis B virus.
      If this association is causal and viral carriage predisposes to severe malaria,
      widespread vaccination against hepatitis B virus may reduce mortality from severe
      malaria.

PMID- 7585072
TI  - Genes and discrimination.

PMID- 7585073
TI  - Science, medicine and Golgi.

PMID- 7585074
TI  - Apoptosis and HIV disease.

PMID- 7585075
TI  - MHC molecular mimicry in diabetes.

PMID- 7585076
TI  - Tokyo HIV-contaminated blood product hearing.

PMID- 7585077
TI  - Considerable ferment over antifungal agents.

PMID- 7585078
TI  - The patient and the public good.

PMID- 7585079
TI  - Nudging xenotransplantation towards humans.

PMID- 7585080
TI  - Deficient diet evokes nasty heart virus.

PMID- 7585081
TI  - A 'senseless' immune response to DNA.

PMID- 7585082
TI  - Getting to know you: viruses meet CD40 ligand.

PMID- 7585083
TI  - Testing anti-HIV drugs in the FIV model.

PMID- 7585085
TI  - Slowing ageing by caloric restriction.

PMID- 7585084
TI  - A foundation for limb-girdle muscular dystrophy.

PMID- 7585086
TI  - CRH, a placental clock and preterm labour.

PMID- 7585087
TI  - Mitochondrial toxicity of antiviral drugs.
AB  - Long-term treatment with antiviral nucleoside analogue drugs, such as AZT, can
      give rise to delayed and at times severe mitochondrial toxicity. Although these
      toxic effects are manifest in many tissues, a common disease mechanism can
      explain the diverse clinical events. A better understanding of these disorders
      will shed light on genetic mitochondrial diseases and lead to the design of safer
      and more effective antiviral drugs.

PMID- 7585088
TI  - Human complement regulatory proteins protect swine-to-primate cardiac xenografts
      from humoral injury.
AB  - The susceptibility of xenografts to hyperacute rejection is postulated to reflect
      in part failure of complement regulatory proteins (CRPs) to control activation of
      heterologous complement on graft endothelium. To test this concept, transgenic
      swine expressing the human CRP decay accelerating factor and CD59 were developed
      using a novel expression system involving transfer of the proteins from
      erythrocytes to endothelial cells. Hearts from transgenic swine transplanted into
      baboons had markedly less vascular injury and functioned for prolonged periods
      compared to hearts from nontransgenic swine. These results indicate that
      expression of human CRPs in xenogeneic organs may contribute to successful
      xenografting and suggest that intercellular protein transfer might be a useful
      approach for expression of heterologous proteins in endothelial cells.

PMID- 7585089
TI  - The essential roles of parenchymal tissues and passenger leukocytes in the
      tolerance induced by liver grafting in rats.
AB  - Liver allografts in pigs and rodents are uniquely capable of inducing tolerance
      to themselves and to other grafts of donor tissues, instead of succumbing to the
      acute rejection that follows transplantation of other allogeneic tissues. We
      demonstrate here, using normal and chimaeric rat liver grafts, that both the
      allogeneic liver parenchyma and the intrahepatic leukocytes of donor type
      contribute to the establishment of long-term tolerance, each component being
      essential and complementary. The essential role of hepatic parenchyma may be
      related to its continuous release of soluble transplantation antigens that
      facilitate tolerogenesis. We suggest that clinical attempts at tolerance
      induction by the infusion of donor bone marrow-derived leukocytes may likewise be
      facilitated by the coadministration of soluble transplantation antigens of donor
      type.

PMID- 7585090
TI  - Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient
      mice results in selection of identical virulent isolates.
AB  - Previous work from our laboratory demonstrated that selenium deficiency in the
      mouse allows a normally benign (amyocarditic) cloned and sequenced Coxackievirus
      to cause significant heart damage. Furthermore, Coxsackievirus recovered from the
      hearts of selenium-deficient mice inoculated into selenium-adequate mice still
      induced significant heart damage, suggesting that the amyocarditic Coxsackievirus
      had mutated to a virulent phenotype. Here we report that sequence analysis
      revealed six nucleotide changes between the virulent virus recovered from the
      selenium-deficient host and the avirulent input virus. These nucleotide changes
      are consistent with known differences in base composition between virulent and
      avirulent strains of Coxsackievirus. To the best of our knowledge, this is the
      first report of a specific nutritional deficiency driving changes in a viral
      genome, permitting an avirulent virus to acquire virulence due to genetic
      mutation.

PMID- 7585091
TI  - CD40 ligand has potent antiviral activity.
AB  - For B cells to make antibodies against most antigens, they require help from T
      cells. T cell help is delivered as two signals to the B cell, one of which is via
      CD40 and the other can be through receptors for any of a variety of soluble
      cytokines. We have constructed recombinant vaccinia viruses that express the
      ligand for CD40 and have shown that the growth of these viruses is dramatically
      controlled in vivo, even in mice that lack T or B cells. In this paper, we also
      describe our attempts to analyse the CD40 ligand-mediated antiviral activity by
      studying the clearance of these viruses in mice that are deficient in important
      antiviral mechanisms. Thus, the antiviral activity of CD40L may represent a
      surprising and potent effector mechanism of T cells activated during a virus
      infection.

PMID- 7585092
TI  - Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a
      primary immune, but not keratinocyte, pathogenic basis.
AB  - Psoriasis is a hyperproliferative and inflammatory skin disorder of unknown
      aetiology. A fusion protein composed of human interleukin-2 and fragments of
      diphtheria toxin (DAB389IL-2), which selectively blocks the growth of activated
      lymphocytes but not keratinocytes, was administered systemically to ten patients
      to gauge the contribution of activated T cells to the disease. Four patients
      showed striking clinical improvement and four moderate improvement, after two
      cycle of low dose IL-2-toxin. The reversal of several molecular markers of
      epidermal dysfunction was associated with a marked reduction in intraepidermal
      CD3+ and CD8+ T cells, suggesting a primary immunological basis for this
      widespread disorder.

PMID- 7585093
TI  - Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ
      antigenic determinant in patients with early rheumatoid arthritis.
AB  - A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid
      arthritis (RA) by bacterial antigens that activate T lymphocytes previously
      'educated' by peptides derived from a class of human histocompatibility antigens
      is reported here. These antigens have the amino acid sequence QKRAA, which is
      also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid
      cells of early RA patients have strong immune responses to the bacterial antigen,
      but cells from normal subjects or controls with other autoimmune diseases do not.
      The activated T cells may cross-react with autologous dnaJ heat-shock proteins
      that are expressed at synovial sites of inflammation. Our findings may have
      direct relevance to new strategies for the immune therapy of RA.

PMID- 7585094
TI  - Ischaemia-induced expression of bFGF in normal skeletal muscle: a potential
      paracrine mechanism for mediating angiogenesis in ischaemic skeletal muscle.
AB  - To test the hypothesis that induction of endogenous bFGF can lead to angiogenesis
      in ischaemic skeletal muscle, we studied the expression of bFGF after
      transposition of a well-vascularized muscle flap onto an ischaemic hindlimb in
      the rabbit. The results indicated a marked induction of bFGF mRNA throughout the
      myoblasts of the well-perfused muscle flap but not the myoblasts of the ischaemic
      muscle. bFGF protein was detected in the muscle flap, particularly in the
      myoblasts located closest to a newly formed, adjacent interface, and in the
      interface itself. In contrast, bFGF expression was not induced after
      transposition of a well-perfused muscle flap onto healthy muscle tissue. These
      data provide evidence that the juxtaposition of ischaemic skeletal muscle with
      healthy mesenchymal tissue triggers an increased expression of bFGF in the
      myoblasts of the well-perfused muscle. This paracrine induction of bFGF, in turn,
      leads to increased angiogenesis and regeneration of the ischaemic skeletal
      muscle.

PMID- 7585095
TI  - A placental clock controlling the length of human pregnancy.
AB  - We report the existence of a 'placental clock', which is active from an early
      stage in human pregnancy and determines the length of gestation and the timing of
      parturition and delivery. Using a prospective, longitudinal cohort study of 485
      pregnant women we have demonstrated that placental secretion of corticotropin
      releasing hormone (CRH) is a marker of this process and that measurement of the
      maternal plasma CRH concentration as early as 16-20 weeks of gestation identifies
      groups of women who are destined to experience normal term, preterm or post-term
      delivery. Further, we report that the exponential rise in maternal plasma CRH
      concentrations with advancing pregnancy is associated with a concomitant fall in
      concentrations of the specific CRH binding protein in late pregnancy, leading to
      a rapid increase in circulating levels of bioavailable CRH at a time that
      coincides with the onset of parturition, suggesting that CRH may act directly as
      a trigger for parturition in humans.

PMID- 7585096
TI  - The association of an HPV16 oncogene variant with HLA-B7 has implications for
      vaccine design in cervical cancer.
AB  - HLA-restricted cytotoxic T-lymphocyte (CTL) recognition of human papillomavirus
      (HPV) oncogene products may be important in the control of the HPV infections
      associated with the development of cervical cancer. We have identified, in HLA-B7
      individuals, a consistent variation in the HPV16 E6 oncoprotein sequence, which
      alters an HLA-B7 peptide binding epitope in a way likely to influence immune
      recognition by CTLs. These results illustrate a biologically relevant mechanism
      for escape from immune surveillance of HPV16 in HLA-B7 individuals. Thus, both
      HLA type and HPV16 strain variation need to be considered in the screening of at
      risk individuals and for the rational design of anti-HPV vaccines.

PMID- 7585097
TI  - A recombinant Listeria monocytogenes vaccine expressing a model tumour antigen
      protects mice against lethal tumour cell challenge and causes regression of
      established tumours.
AB  - Listeria monocytogenes is an intracellular organism that has the unusual ability
      to live in the cytoplasm of the cell. It is thus a good vector for targeting
      protein antigens to the cellular arm of the immune response. Here we use a model
      system, consisting of colon and renal carcinomas that express the influenza virus
      nucleoprotein and a recombinant L. monocytogenes that secrets this antigen, to
      test the potential of this organism as a cancer immunotherapeutic agent. We show
      that this recombinant organism can not only protect mice against lethal challenge
      with tumour cells that express the antigen, but can also cause regression of
      established macroscopic tumours in an antigen-specific T-cell-dependent manner.

PMID- 7585098
TI  - Gene gun and other non-viral approaches for cancer gene therapy.

PMID- 7585099
TI  - Biotechnology and God.

PMID- 7585101
TI  - Psychiatry disabused.

PMID- 7585100
TI  - Psychiatry disabused.

PMID- 7585102
TI  - Psychiatry disabused.

PMID- 7585103
TI  - The role of clinical research.

PMID- 7585104
TI  - Blood safety.

PMID- 7585105
TI  - Blood safety.

PMID- 7585106
TI  - The PKD1 gene product.

PMID- 7585107
TI  - 'Bypass' budget reveals AIDS research funding priorities.

PMID- 7585108
TI  - A new representation of knowledge concerning human anatomy and function.
AB  - By integrating concepts of computer graphics and artificial intelligence, novel
      ways of representing medical knowledge become possible. They allow unprecedented
      possibilities ranging from three-dimensional interactive atlases to systems for
      surgery rehearsal.

PMID- 7585109
TI  - Bringing cell growth research together.

PMID- 7585110
TI  - Cascading towards vascular disorder gene therapy.

PMID- 7585112
TI  - Measuring NO2 exposure in respiratory disease.

PMID- 7585111
TI  - Nitric oxide in mucosal immunity.

PMID- 7585113
TI  - Rational drug design and HIV: hopes and limitations.

PMID- 7585114
TI  - Paving the way towards DNA vaccines.

PMID- 7585115
TI  - G protein gene knockout hits the gut.

PMID- 7585116
TI  - Molecular struggle for transcriptional control.

PMID- 7585117
TI  - Multidrug resistance: locked in the vault?

PMID- 7585118
TI  - A single-injection protein kinase A-directed antisense treatment to inhibit
      tumour growth.
AB  - Expression of the RI alpha subunit of cAMP-dependent protein kinase type I is
      enhanced in human cancer cell lines, in primary tumours, in cells after
      transformation and in cells upon stimulation of growth. We have investigated the
      effect of sequence-specific inhibition of RI alpha gene expression on in vivo
      tumour growth. We report that single injection RI alpha antisense treatment
      results in a reduction in RI alpha expression and inhibition of tumour growth.
      Tumour cells behaved like untransformed cells by making less protein kinase type
      I. The RI alpha antisense, which produces a biochemical imprint for growth
      control, requires infrequent dosing to halt neoplastic growth in vivo.

PMID- 7585119
TI  - Clotrimazole inhibits cell proliferation in vitro and in vivo.
AB  - Cell proliferation is critically dependent on the regulated movement of ions
      across various cellular compartments. The antimycotic drug clotrimazole (CLT) has
      been shown to inhibit movement of Ca2+ and K+ across the plasma membrane. Our
      results show that CLT inhibits the rate of cell proliferation of normal and
      cancer cell lines in a reversible and dose-dependent manner in vitro. Moreover,
      CLT depletes the intracellular Ca2+ stores and prevents the rise in cytosolic
      Ca2+ that normally follows mitogenic stimulation. In mice with severe combined
      immunodeficiency disease (SCID) and inoculated intravenously with MM-RU human
      melanoma cells, daily subcutaneous injections of CLT induced a significant
      reduction in the number of lung metastases. Modulation of early ionic mitogenic
      signals and potent inhibition of cell proliferation both in vitro and in vivo are
      new and potentially useful clinical effects of CLT.

PMID- 7585120
TI  - Inhibition of cellular ras prevents smooth muscle cell proliferation after
      vascular injury in vivo.
AB  - Proliferation of smooth muscle cells of the arterial wall in response to local
      injury is an important aetiologic factor of vascular proliferative disorders such
      as atherosclerosis and restenosis after angioplasty. Ras proteins are key
      transducers of mitogenic signals from membrane to nucleus in many cell types. We
      investigated the role of ras proteins in the vascular response to arterial injury
      by inactivating cellular ras of rats in which the common carotid artery was
      subjected to balloon injury. DNA vectors expressing ras transdominant negative
      mutants, which interfere with ras function, reduced neointimal formation after
      injury. Our results indicate a key role for ras in smooth muscle cell
      proliferation and show that the local delivery of transdominant negative mutants
      of ras in vivo might prevent some of the acute vascular injury caused by balloon
      injury.

PMID- 7585121
TI  - Chemical generation of nitric oxide in the mouth from the enterosalivary
      circulation of dietary nitrate.
AB  - High concentrations of nitrite present in saliva (derived from dietary nitrate)
      may, upon acidification, generate nitrogen oxides in the stomach in sufficient
      amounts to provide protection from swallowed pathogens. We now show that, in the
      rat, reduction of nitrate to nitrite is confined to a specialized area on the
      posterior surface of the tongue, which is heavily colonized by bacteria, and that
      nitrate reduction is absent in germ-free rats. We also show that in humans
      increased salivary nitrite production resulting from nitrate intake enhances oral
      nitric oxide production. We propose that the salivary generation of nitrite is
      accomplished by a symbiotic relationship involving nitrate-reducing bacteria on
      the tongue surface, which is designed to provide host defence against microbial
      pathogens in the mouth and lower gut. These results provide further evidence for
      beneficial effects of dietary nitrate.

PMID- 7585122
TI  - Gamma delta T cell-induced nitric oxide production enhances resistance to mucosal
      candidiasis.
AB  - Despite the prevalence of gamma delta T cells in mucosae that are typically
      colonized by Candida albicans, little is known of the possible role of these
      cells in resistance to candidiasis. A sharp increase in the number of gamma delta
      T cells and macrophages following intraperitoneal inoculation of mice with C.
      albicans led us to examine the role of these cells in the immune response to C.
      albicans. We show that the gamma delta T cells enhance macrophage nitric oxide
      (NO) production and anti-candida activity, in vitro. We also propose that the
      gamma delta T cells regulate macrophage function during candidiasis in vivo as
      well, because depletion of these cells abrogated inducible NO synthase expression
      in mucosae and enhanced murine susceptibility to candidiasis.

PMID- 7585123
TI  - Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine
      arthritis.
AB  - A ubiquitous cell adhesion receptor, CD44, preferentially binds hyaluronan, a
      polysaccharide macromolecule that is present in most extracellular matrices.
      Hyaluronan molecules have large hydrodynamic volumes that entrap substantial
      amounts of water and can therefore control tissue hydration (swelling). CD44 is
      overexpressed by synovial cells and leukocytes, and hyaluronan is overproduced in
      the rheumatoid synovium and in other inflammatory sites. Nevertheless, the role
      of the CD44-hyaluronan interaction during inflammation is unclear. Our evidence
      shows that the CD44 receptor plays a critical role in governing the migration of
      inflammatory leukocytes into the extravascular compartment of the synovium in
      murine arthritis. An anti-CD44 antibody induces a rapid loss of CD44 from both
      leukocytes and synovial cells and displays an inhibitory effect on cell
      extracellular matrix interactions in the synovium. As a result, the
      administration of such an antibody abrogates tissue swelling and leukocyte
      infiltration, two major components of inflammation.

PMID- 7585124
TI  - Isolation of novel virus-like sequences associated with human hepatitis.
AB  - Two viruses, GB virus A (GBV-A) and GB virus B (GBV-B), were recently identified
      in the GB hepatitis agent. Human sera containing antibodies that recognize GBV-A
      and/or GBV-B recombinant proteins were subjected to polymerase chain reaction
      studies with degenerate oligonucleotides capable of amplifying a segment of the
      putative helicase genes from GBV-A, GBV-B or hepatitis C virus. Novel sequences
      related to members of the Flaviviridae were identified in sera from 12
      individuals including 4 individuals with hepatitis. The limited nucleotide
      sequence identity between GBV-A, GBV-B and HCV sequences suggests that a novel
      virus, tentatively named GB virus C, may be responsible for some cases of non-A,
      non-B, non-C, non-D, non-E hepatitis.

PMID- 7585125
TI  - p53 activates expression of HIC-1, a new candidate tumour suppressor gene on
      17p13.3.
AB  - For several human tumour types, allelic loss data suggest that one or more tumour
      suppressor genes reside telomeric to the p53 gene at chromosome 17p13.1. In the
      present study we have used a new strategy, involving molecular analysis of a DNA
      site hypermethylated in tumour DNA, to identify a candidate gene in this region
      (17p13.3). Our approach has led to identification of HIC-1 (hypermethylated in
      cancer), a new zinc-finger transcription factor gene which is ubiquitously
      expressed in normal tissues, but underexpressed in different tumour cells where
      it is hypermethylated. Multiple characteristics of this gene, including the
      presence of a p53 binding site in the 5' flanking region, activation of the gene
      by expression of a wild-type p53 gene and suppression of G418 selectability of
      cultured brain, breast and colon cancer cells following insertion of the gene,
      make HIC-1 gene a strong candidate for a tumour suppressor gene in region
      17p13.3.

PMID- 7585126
TI  - The drug resistance-related protein LRP is the human major vault protein.
AB  - Multidrug-resistant cancer cells frequently overexpress the 110-kD LRP protein
      (originally named Lung Resistance-related Protein). LRP overexpression has been
      found to predict a poor response to chemotherapy in acute myeloid leukaemia and
      ovarian carcinoma. We describe the cloning and chromosome localization of the
      gene coding for this novel protein. The deduced LRP amino acid sequence shows
      87.7% identity with the 104-kD rat major vault protein. Vaults are multi-subunit
      structures that may be involved in nucleo-cytoplasmic transport. The LRP gene is
      located on chromosome 16, close to the genes coding for multidrug resistance
      associated protein and protein kinase C-beta, and may mediate drug resistance,
      perhaps via a transport process.

PMID- 7585127
TI  - Preclinical efficacy of a prototype DNA vaccine: enhanced protection against
      antigenic drift in influenza virus.
AB  - Vaccination with plasmid DNA expression vectors encoding foreign proteins elicits
      antibodies and cell-mediated immunity and protects against disease in animal
      models. We report a comparison of DNA vaccines, using contemporary human strains
      of virus, and clinically licensed (inactivated virus or subvirion) vaccines in
      preclinical animal models, to better predict their efficacy in humans. Influenza
      DNA vaccines elicited antibodies in both non-human primates and ferrets and
      protected ferrets against challenge with an antigenically distinct epidemic human
      influenza virus more effectively than the contemporary clinically licensed
      vaccine. These studies demonstrate that DNA vaccines may be more effective,
      particularly against different strains of virus, than inactivated virus or
      subvirion vaccines.

PMID- 7585128
TI  - Genome engineering: the new mouse genetics.

PMID- 7585130
TI  - Aspirin, salicylate and gastrointestinal injury.

PMID- 7585129
TI  - Wanted: a few good ideas.

PMID- 7585131
TI  - Head injury, amyloid beta and Alzheimer's disease.

PMID- 7585133
TI  - Euthanasia. Should anyone be denied the freedom to commit suicide?

PMID- 7585132
TI  - Electroconvulsive therapy for children.

PMID- 7585134
TI  - T-cell dynamics of immunodeficiency.

PMID- 7585136
TI  - Dopamine transporter, alcoholism and other diseases.

PMID- 7585135
TI  - The psychobiological regulation of social cooperation.

PMID- 7585138
TI  - Targeting HIV reverse transcriptase in novel ways.

PMID- 7585137
TI  - Identifying the killer in cystic fibrosis.

PMID- 7585139
TI  - Mental health in low-income countries.

PMID- 7585141
TI  - Methylation and p16: suppressing the suppressor.

PMID- 7585140
TI  - A target for tumour-directed therapy.

PMID- 7585142
TI  - To metastasize or not? Selection of CD44 splice sites.

PMID- 7585143
TI  - Effects of the MYC oncogene antagonist, MAD, on proliferation, cell cycling and
      the malignant phenotype of human brain tumour cells.
AB  - To investigate how overexpression of MAD, an antagonist of MYC oncogenes
      influences the malignant phenotype of human cancer cells, an adenovirus vector
      system was used to transfer the human MAD gene (AdMAD) into human astrocytoma
      cells. Decreased growth potential of AdMAD-infected cells was evidenced by a
      decrease in [3H]thymidine incorporation, an increase in cell doubling time and
      alteration of cell-cycle distribution. Diminished malignant potential of AdMAD
      infected cells was manifested by their loss of anchorage-independent growth in
      soft agar and by their inability, in general, to induce tumorigenesis in a
      xenograft animal model. These studies indicate that adenovirus constructs
      encoding MAD dramatically inhibit the proliferation and tumorigenicity of human
      astrocytoma cells and support the use of MAD for gene therapy of human tumours.

PMID- 7585144
TI  - Prevention of breast tumour development in vivo by downregulation of the p185neu
      receptor.
AB  - Certain strains of transgenic mice that express the rat neu oncogene (neuT) in
      mammary epithelial cells develop breast tumours at an average of 44 weeks of age.
      In this study, intraperitoneal injection of a monoclonal anti-receptor antibody
      specific for the rat neuT oncogene product dramatically affected tumour
      development in these transgenic mice in a dose-dependent manner. A significant
      proportion (50%) of mice, when injected with anti-receptor antibodies, did not
      develop tumours even after 90 weeks of age. The phosphotyrosine levels of the
      membrane fraction of breast tissues in the anti-receptor antibody-treated mice
      were almost completely abolished when a higher dose of antibodies was used. This
      study demonstrates, for the first time, that immunologic manipulation of an
      oncogene product can effectively prevent the development of tumours in a rodent
      transgenic model.

PMID- 7585145
TI  - Targeting antigen into the phagocytic pathway in vivo induces protective tumour
      immunity.
AB  - Cytotoxic T lymphocytes (CTLs) kill neoplastic or virally infected cells after
      recognizing on their surface antigenic peptides bound to major histocompatibility
      complex class I molecules. These peptides are derived from antigens that are
      degraded in the cytosol of the affected cell. Because exogenous proteins cannot
      enter the cytosol, immunizations with killed pathogens or their proteins do not
      generally elicit CTLs. However, antigens that are internalized into phagocytic
      cells can enter the cytosol and be processed for class I presentation. Here we
      show that immunization with a purified antigen on an avidly phagocytized particle
      primes CTLs, which in turn protect animals from subsequent challenge with tumours
      transfected with the antigen gene. Interestingly, these animals also become
      immune to other antigens expressed by the tumour. This approach could be
      exploited to develop tumour and viral vaccines.

PMID- 7585146
TI  - Altered striatal dopamine re-uptake site densities in habitually violent and non
      violent alcoholics.
AB  - Animal studies suggest that development of substance dependence is associated
      with dopaminergic activity in striatum and the limbic system. Several genetic
      studies indicate that allele A1 is associated with both D2 receptor density and
      alcoholism, although these findings have remained controversial. We studied
      striatal dopamine (DA) re-uptake site densities in 48 subjects (19 healthy
      controls, 19 habitually impulsive violent alcoholics, and 10 non-violent
      alcoholics) with single photon emission computed tomography (SPECT) using iodine
      123-labelled 2 beta-carbomethoxy-3 beta(4-iodophenyl)tropane, (beta-CIT) as a
      tracer. Blind quantitative analysis revealed that the striatal DA transporter
      density was markedly lower in non-violent alcoholics than in healthy controls (P
      < 0.001), while violent alcoholics had slightly higher DA transporter densities
      than controls (P < 0.10). The results indicate that both types of alcoholics have
      alterations in striatal dopaminergic system, though these occur in opposite
      directions.

PMID- 7585147
TI  - Brain stem activation in spontaneous human migraine attacks.
AB  - Evidence from animal experiments shows that the brain stem is involved in the
      pathophysiology of migraine. To investigate human migraine, we used positron
      emission tomography to examine the changes in regional cerebral blood flow as an
      index of neuronal activity in the human brain during spontaneous migraine
      attacks. During the attacks, increased blood flow was found in the cerebral
      hemispheres in cingulate, auditory and visual association cortices and in the
      brain stem. However, only the brain stem activation persisted after the injection
      of sumatriptan had induced complete relief from headache and phono- and
      photophobia. These findings support the idea that the pathogenesis of migraine is
      related to an imbalance in activity between brain stem nuclei regulating
      antinociception and vascular control.

PMID- 7585148
TI  - The emergence of a highly transmissible lineage of cbl+ Pseudomonas
      (Burkholderia) cepacia causing CF centre epidemics in North America and Britain.
AB  - The rapid increase in Pseudomonas (Burkholderia) cepacia infection in cystic
      fibrosis (CF) patients suggests epidemic transmission, but the degree of
      transmissibility remains controversial as conflicting conclusions have been drawn
      from studies at different CF centres. This report provides the first DNA sequence
      based documentation of a divergent evolutionary lineage of P. cepacia associated
      with CF centre epidemics in North America (Toronto) and Europe (Edinburgh). The
      involved epidemic clone encoded and expressed novel cable (Cbl) pili that bind to
      CF mucin. The sequence of the cblA pilin subunit gene carried by the epidemic
      isolates proved to be invariant. Although it remains to be determined how many
      distinct, highly transmissible lineages exist, our results provide both a DNA
      sequence and chromosomal fingerprint that can be used to screen for one such
      particularly infectious, transatlantic clone.

PMID- 7585149
TI  - Intracellular expression of antibody fragments directed against HIV reverse
      transcriptase prevents HIV infection in vitro.
AB  - We have tested a novel strategy of intracellular immunization to block human
      immunodeficiency virus (HIV) infection. The expression of a specific antibody
      within a cell was achieved by transduction of genes that encode for
      immunoglobulin chains with specificity to viral reverse transcriptase. We
      demonstrated that inhibition of this enzyme makes cells resistant to HIV
      infection by blocking an early stage of viral replication. If high efficiency
      transduction with a stable vector into lymphohaematopoietic stem cells or mature
      lymphocytes can be achieved, gene transfer-mediated intracellular immunization
      might be a feasible treatment strategy in AIDS.

PMID- 7585150
TI  - Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter
      AIDS Cohort Study.
AB  - We and others have postulated that a constant number of T lymphocytes is normally
      maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis).
      Here we confirm essentially constant T-cell levels (despite marked decline in
      CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human
      immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired
      immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In
      contrast, seroconverters who developed AIDS exhibited rapidly declining T cells
      (both CD4+ and CD8+) for approximately two years before AIDS, independent of the
      time between seroconversion and AIDS, suggesting that homeostasis failure is an
      important landmark in HIV disease progression. Given the high rate of T-cell
      turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV
      pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of
      lost CD4+ T cells.

PMID- 7585151
TI  - Neutralization of HIV-1 by secretory IgA induced by oral immunization with a new
      macromolecular multicomponent peptide vaccine candidate.
AB  - Control of pandemic infection of human immunodeficiency virus type 1 (HIV-1)
      requires some means of developing mucosal immunity against HIV-1 because sexual
      transmission of the virus occurs mainly through the mucosal tissues. However,
      there is no evidence as yet that the secretory immunoglobulin A (IgA) antibody
      induced by immunization with antigens in experimental animals can neutralize HIV
      1. We demonstrate here that oral immunization with a new macromolecular peptide
      antigen and cholera toxin (CT) induces a high titre (1:2") of gut-associated and
      secretory IgA antibody to HIV-1. Using three different neutralizing assays, we
      clearly demonstrate that this secretory IgA antibody is able to neutralize HIV
      1IIIB, HIV-1SF2 and HIV-1MN. Our new approach may prove to be important in the
      development of a mucosal vaccine that will provide protection of mucosal surfaces
      against HIV-1.

PMID- 7585152
TI  - 5' CpG island methylation is associated with transcriptional silencing of the
      tumour suppressor p16/CDKN2/MTS1 in human cancers.
AB  - Loss of heterozygosity on chromosome 9p21 is one of the most frequent genetic
      alterations identified in human cancer. The rate of point mutations of p16, a
      candidate suppressor gene of this area, is low in most primary tumours with
      allelic loss of 9p21. Monosomic cell lines with structurally unaltered p16 show
      methylation of the 5' CpG island of p16. This distinct methylation pattern was
      associated with a complete transcriptional block that was reversible upon
      treatment with 5-deoxyazacytidine. Moreover, de novo methylation of the 5' CpG
      island of p16 was also found in approximately 20% of different primary neoplasms,
      but not in normal tissues, potentially representing a common pathway of tumour
      suppressor gene inactivation in human cancers.

PMID- 7585153
TI  - Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant
      stress resulting in cytokine gene expression and release of amyloid beta-peptide.
AB  - Paired helical filament (PHF) tau is the principal component of neurofibrillary
      tangles, a characteristic feature of the neurodegenerative pathology in
      Alzheimer's disease (AD). Post-translational modification of tau, especially
      phosphorylation, has been considered a major factor in aggregation and diminished
      microtubule interactions of PHF-tau. Recently, it has been recognized that PHF
      tau is also subject to non-enzymatic glycation, with formation of advanced
      glycation end products (AGEs). We now show that as a consequence of glycation,
      PHF-tau from AD and AGE-tau generate oxygen free radicals, thereby activating
      transcription via nuclear factor-kappa B, increasing amyloid beta-protein
      precursor and release of approximately 4 kD amyloid beta-peptides. These data
      provide insight into how PHF-tau disturbs neuronal function, and add to a growing
      body of evidence that oxidant stress contributes to the pathogenesis of AD.

PMID- 7585154
TI  - Serum p53 antibodies as early markers of lung cancer.
AB  - The p53 alteration is the most common alteration found in human cancer. It
      usually involves missense mutations that stabilize the p53 protein, which in turn
      accumulates, reaching levels detectable by immunohistochemistry. We and others
      have demonstrated that this overexpression of mutant p53 protein can induce a
      specific humoral response in cancer patients. This result was assessed by the
      presence of p53 antibodies in sera of patients with various types of cancers,
      whereas normal populations do not exhibit such antibodies. In lung cancer, the
      prevalence of p53 antibodies is high (30%) and is correlated with a very high
      rate of p53 mutations in this cancer (60-70%). We show that these antibodies are
      always present at the time of diagnosis, but never appear during tumour
      development, an observation strengthened by the fact that these antibodies are
      mostly IgG, corresponding to a secondary immune response. These results suggest
      that the humoral response is an early event and that p53 antibodies can be used
      as a precocious marker of p53 alteration before clinical manifestation of the
      disease.

PMID- 7585155
TI  - Protection against bronchial asthma by CFTR delta F508 mutation: a heterozygote
      advantage in cystic fibrosis.
AB  - Cystic fibrosis (CF) is a multisystem autosomal recessive disorder caused by
      mutations of the cystic fibrosis transmembrane regulator (CFTR), a protein that
      regulates cyclic-AMP-mediated chloride conductance at the apical membrane of
      secretory epithelia. Mutations in the CFTR gene are common in many populations.
      In North America, 4-5% of the general population are heterozygous for a CFTR
      mutation. Although there are over 400 known CFTR mutations, a single mutation, a
      deletion of the phenylalanine at position 508 (delta F508) in exon 10, accounts
      for about 70% of all CF chromosomes worldwide. The reasons for the high frequency
      of the delta F508 CFTR allele--the selective advantage associated with CF
      heterozygosity--are unknown. Many physiological abnormalities have been observed
      in CF heterozygotes, although the clinical significance of these observations is
      unknown. Preliminary unpublished data and anecdotal information from CF families
      suggested that, remarkably, the delta F508 allele might protect heterozygotes
      against bronchial asthma prompted us to further investigate this possibility.
      Here we present evidence that the delta F508 CF allele protects against asthma in
      childhood and early adult life.

PMID- 7585157
TI  - The feasibility of targeted selective gene therapy of the hair follicle.
AB  - Loss of hair and hair colour is associated with ageing, and when it involves the
      scalp hair, it can be distressing to both sexes. Hair loss resulting from cancer
      chemotherapy is particularly distressing. However, safe, effective therapies
      directed to hair have only just started to be developed. The hair follicle is a
      complex skin appendage composed of epidermal and dermal tissue, with specialized
      keratinocytes, the hair matrix cells, forming the hair shaft. Specific therapy of
      the hair follicle depends on selective targeting of specific cells of the hair
      follicle. We have developed the histoculture of intact hair-growing skin on
      sponge-gel matrices. We have recently found in histocultured skin that liposomes
      can selectively target hair follicles to deliver both small and large molecules.
      That liposomes can target the hair follicle for delivery has been confirmed
      independently. Two decades ago we introduced the technique of entrapping DNA in
      liposomes for use in gene therapy. In this report we describe the selective
      targeting of the lacZ reporter gene to the hair follicles in mice after topical
      application of the gene entrapped in liposomes. These results demonstrate that
      highly selective, safe gene therapy for the hair process is feasible.

PMID- 7585156
TI  - A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is a previously rare, tumour-like lesion of controversial
      biological nature. KS has since the early 1980s become frequent in patients with
      AIDS, particularly in homosexuals. KS is also endemic in Central Africa
      predominantly in otherwise healthy men but also in women and children. Recently,
      evidence for the presence of novel, herpes virus DNA sequences in more than 90%
      of AIDS Kaposi lesions (AKS) was presented. This DNA was identified using
      representational difference analysis (RDA) generating short, unique sequences
      with variable homology to several herpes virus, but no intact virus was
      recovered. If these DNA-sequences are also present in other, non-HIV-associated
      forms of Kaposi's sarcoma this would strongly suggest a specific,
      aetiopathological involvement of this putative new herpes virus in the
      pathogenesis of Kaposi's sarcoma, rather than a contamination of yet another
      opportunistic virus in immunosuppressed AIDS patients.

PMID- 7585158
TI  - Magnetic resonance of the heart and great vessels.

PMID- 7585160
TI  - Defining the risk in health insurance.

PMID- 7585159
TI  - The hostile takeover of medicine.

PMID- 7585161
TI  - Bromocriptine in the treatment of alcoholics.

PMID- 7585162
TI  - . . . and anatomical research.

PMID- 7585163
TI  - More sober research...

PMID- 7585164
TI  - CDC and Congress at odds over mandatory HIV testing.

PMID- 7585165
TI  - What direction for AIDS drug task force?

PMID- 7585166
TI  - Scandal touches HIV vaccine development in Japan.

PMID- 7585167
TI  - Can results from clinical trials be generalized?
AB  - Randomized clinical trials are powerful tools to refute old prejudices and
      establish new therapeutic regimes. We propose that they should be afforded a more
      widespread application in modern clinical medicine.

PMID- 7585168
TI  - Monkey eyes grow into focus.

PMID- 7585171
TI  - Genomic prospecting.

PMID- 7585172
TI  - Transfection and malaria.

PMID- 7585169
TI  - Metastases suppressors and prostate cancer.

PMID- 7585170
TI  - Independent mechanisms converge on pain.

PMID- 7585173
TI  - Rational cancer therapy.

PMID- 7585175
TI  - The rise and fall and rise of tuberculosis.

PMID- 7585174
TI  - Heart and lung disease in engineered mice.

PMID- 7585176
TI  - Human retroviruses in the second decade: a personal perspective.
AB  - Human retroviruses have developed novel strategies for their propagation and
      survival. A consequence of their success has been the induction of an
      extraordinarily diverse set of human diseases, including AIDS, cancers and
      neurological and inflammatory disorders. Early research focused on their
      characterization, linkage to these diseases, and the mechanisms involved.
      Research should now aim at the eradication of human retroviruses and on treatment
      of infected people.

PMID- 7585177
TI  - Spectacle lenses alter eye growth and the refractive status of young monkeys.
AB  - The influence of visual experience on ocular development in higher primates is
      not well understood. To investigate the possible role of defocus in regulating
      ocular growth, spectacle lenses were used to optically simulate refractive
      anomalies in young monkeys (for example, myopia or nearsightedness). Both
      positive and negative lenses produced compensating ocular growth that reduced the
      lens-induced refractive errors and, at least for low lens powers, minimized any
      refractive-error differences between the two eyes. These results indicate that
      the developing primate visual system can detect the presence of refractive
      anomalies and alter each eye's growth to eliminate these refractive errors.
      Moreover, these results support the hypothesis that spectacle lenses can alter
      eye development in young children.

PMID- 7585181
TI  - Spatial and temporal control of gene therapy using ionizing radiation.
AB  - Activation of transcription of the Egr-1 gene by X-rays is regulated by the
      promoter region of this gene. We linked the radiation-inducible promoter region
      of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal
      cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication
      deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in
      nude mice. Combined treatment with Ad5.Egr-TNF and 5,000 cGy (rad) resulted in
      increased intratumoral TNF-alpha production and increased tumour control compared
      with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in
      tumour control was achieved without an increase in normal tissue damage when
      compared to tissue injury from radiation alone. Control of gene transcription by
      ionizing radiation in vivo represents a novel method of spatial and temporal
      regulation of gene-based medical treatments.

PMID- 7585180
TI  - Marked amelioration of established collagen-induced arthritis by treatment with
      antibodies to CD23 in vivo.
AB  - CD23 is a low-affinity receptor for immunoglobulin E (IgE) expressed by a variety
      of haematopoietic cells. Proteolytic cleavage of the transmembrane receptor
      generates soluble forms, which can be detected in biological fluids. CD23
      regulates many functional aspects of immune cells, both in its cell-associated
      and soluble forms. In view of the increased levels of CD23 in rheumatoid
      arthritis, we have studied the effect of neutralizing CD23 in type II collagen
      induced arthritis in mice, a model for human rheumatoid arthritis. Successful
      disease modulation is achieved by treatment of arthritic DBA/1 mice with either
      polyclonal or monoclonal antibodies to mouse CD23. Treated mice show a dose
      related amelioration of arthritis with significantly reduced clinical scores and
      number of affected paws. This improvement in clinical severity is confirmed by
      histological examination of the arthritic paws. A marked decrease in cellular
      infiltration of the synovial sublining layer and limited destruction of cartilage
      and bone is evident in animals treated with therapeutic doses of anti-CD23
      antibody. These findings demonstrate the involvement of CD23 in a mouse model of
      human rheumatoid arthritis.

PMID- 7585179
TI  - The biological effects of endogenous nerve growth factor on adult sensory neurons
      revealed by a trkA-IgG fusion molecule.
AB  - Evidence suggests that nerve growth factor (NGF) may function as a mediator of
      some persistent pain states. We have used a synthetic protein, trkA-IgG, to
      sequester endogenous NGF and block the survival effects of NGF on cultured
      sensory neurons. We show that administration of trkA-IgG produces a sustained
      thermal and chemical hypoalgesia and leads to a downregulation of the sensory
      neuropeptide CGRP (calcitonin gene-related peptide) in treated sensory neurons.
      Acute administration of the molecule blocks the hyperalgesia that develops with
      carrageenan-induced inflammation. These data suggest that peripherally produced
      NGF normally acts to maintain the sensitivity of nociceptive sensory neurons and
      that, in some inflammatory states, an upregulation of NGF is responsible for
      alterations in pain-related behaviour. Antagonists of NGF may therefore be of
      clinical use in treating some chronic pain states.

PMID- 7585178
TI  - Are there separate central nervous system pathways for touch and pain?
AB  - Information about bodily events is conveyed by primary sensory fibres to higher
      brain centres through neurons in the dorsal column nuclei (DCN) and spinal dorsal
      horn. The DCN route is commonly considered a 'touch pathway', separate from the
      spinal pain pathway', in part because DCN neurons respond to gentle tactile
      stimulation of small skin areas. Here we report that DCN neurons can additionally
      respond to gentle and noxious stimulation of viscera and widespread skin regions.
      These and other experimental and clinical data suggest that the DCN and spinal
      routes cooperate, rather than operate separately, to produce the many perceptions
      of touch and pain, an ensemble view that encourages novel approaches to health
      care and research.

PMID- 7585182
TI  - Inhibition of farnesyltransferase induces regression of mammary and salivary
      carcinomas in ras transgenic mice.
AB  - For Ras oncoproteins to transform mammalian cells, they must be post
      translationally modified with a farnesyl group in a reaction catalysed by the
      enzyme farnesyl-protein transferase (FPTase). Inhibitors of FPTase have therefore
      been proposed as anti-cancer agents. We show that L-744,832, which mimics the
      CaaX motif to which the farnesyl group is added, is a potent and selective
      inhibitor of FPTase. In MMTV-v-Ha-ras mice bearing palpable tumours, daily
      administration of L-744,832 caused tumour regression. Following cessation of
      treatment, tumours reappeared, the majority of which regressed upon retreatment.
      No systemic toxicity was found upon necropsy of L-744,832-treated mice. This
      first demonstration of anti-FPTase-mediated tumour regression suggests that
      FPTase inhibitors may be safe and effective anti-tumour agents in some cancers.

PMID- 7585183
TI  - Marfan syndrome as a paradigm for transcript-targeted preimplantation diagnosis
      of heterozygous mutations.
AB  - Among the many clinical applications of the polymerase chain reaction (PCR) is
      its potential use in preimplantation diagnosis of genetic disorders. Performing
      PCR on single blastomeres from early cleavage stage (six- to eight-cell) human
      embryos should, in principle, enable reliable determination of disease status for
      certain inherited conditions. However, reports of misdiagnoses using this
      technique have diminished enthusiasm for its widespread clinical use. One
      principal source of error is the propensity for genome-targeted PCR to
      exclusively amplify one allele in reactions assaying a single heterozygous
      diploid cell. Complete reaction failure is also common. Employing the Marfan
      syndrome (MFS) as a paradigm, we have developed a reliable, reverse transcription
      PCR-based method of genotyping single cells that overcomes these obstacles. The
      technique should facilitate accurate preimplantation diagnosis of MFS and other
      selected genetic diseases caused by heterozygous or compound-heterozygous
      mutations.

PMID- 7585184
TI  - Enzyme-independent formation of nitric oxide in biological tissues.
AB  - The gaseous free radical nitric oxide (NO.) is an important regulator of a
      variety of biological functions and also has a role in the pathogenesis of
      cellular injury. It has been generally accepted that NO. is solely generated in
      biological tissues by specific nitric oxide synthases, NOSs, which metabolize
      arginine to citrulline with the formation of NO.. We report that NO. can also be
      generated in the ischaemic heart by direct reduction of nitrite to NO. under the
      acidotic and highly reduced conditions that occur. This NO. formation is not
      blocked by NOS inhibitors, and with long periods of ischaemia progressing to
      necrosis, this mechanism of NO. formation predominates. We observe that enzyme
      independent NO. generation results in myocardial injury with a loss of
      contractile function. The existence of this enzyme-independent mechanism of NO.
      formation has important implications in our understanding of the pathogenesis and
      treatment of tissue injury.

PMID- 7585185
TI  - The limit of human adaptation to starvation.
AB  - During the height of the 1992-93 famine in Somalia, data were collected from 573
      inpatients at the Concern Worldwide Adult Therapeutic Centre in Baidoa, the town
      at the epicentre of the disaster. These data indicate that a body mass index
      (BMI, body weight in kilograms divided by height in metres squared) of less than
      10 kg m-2 can be compatible with life, so long as specialized care is provided.
      Such low levels of BMI may be explained, in part, by the high ambient
      temperature, the tall phenotype of the Somalis, the gradual reduction in food
      intake and previous exposure to chronic energy deficiency. Famine oedema occurred
      with the same prevalence in male and female patients, but male patients had more
      severe oedema and a poorer prognosis at any given degree of severity. Survival
      from these extremes of emaciation has never before been recorded, and many of the
      BMI values documented here are below the level of 12, previously thought to mark
      the limit of human adaptation to starvation.

PMID- 7585186
TI  - The intrinsic transmission dynamics of tuberculosis epidemics.
AB  - In developed countries the major tuberculosis epidemics declined long before the
      disease became curable in the 1940s. We present a theoretical framework for
      assessing the intrinsic transmission dynamics of tuberculosis. We demonstrate
      that it takes one to several hundred years for a tuberculosis epidemic to rise,
      fall and reach a stable endemic level. Our results suggest that some of the
      decline of tuberculosis is simply due to the natural behaviour of an epidemic.
      Although other factors must also have contributed to the decline, these causal
      factors were constrained to operate within the slow response time dictated by the
      intrinsic dynamics.

PMID- 7585187
TI  - Tumour suppression by the human von Hippel-Lindau gene product.
AB  - A partial cDNA sequence for the gene linked to the von Hippel-Lindau (VHL)
      syndrome was reported in 1993. Mutation or loss of both VHL alleles has been
      documented in sporadic renal cell carcinomas and in the neoplasms that arise in
      von Hippel-Lindau kindreds. We have determined that the protein product of the
      VHL gene is an approximately 30 kilodalton cytoplasmic protein. The renal
      carcinoma cell line 786-O is known to harbour a VHL mutation and, as shown here,
      fails to produce a wild-type VHL protein. Reintroduction of wild-type, but not
      mutant, VHL into these cells had no demonstrable effect on their growth in vitro
      but inhibited their ability to form tumours in nude mice.

PMID- 7585188
TI  - Evidence of an X-linked or recessive genetic component to prostate cancer risk.
AB  - We used data from a population-based cohort study of blacks, Hispanics, Japanese
      and whites to examine the frequency of prevalent prostate and breast cancer by
      family history status of first-degree relatives (parents and siblings).
      Independent of race, the age-adjusted relative risk for prevalent prostate cancer
      in subjects with affected brothers was approximately two times that in subjects
      with affected fathers (P < 0.00005). No such excess risk for breast cancer was
      observed among subjects with affected sisters compared to those with affected
      mothers (age- and race-adjusted relative risk = 1.10, P = 0.34). The magnitude of
      the relative risk for prostate cancer in sibling- versus parent-affected groups
      was significantly different from that of the comparable relative risk for breast
      cancer (P < 0.00005). An excess risk of prostate cancer in men with affected
      brothers compared to those with affected fathers is consistent with the
      hypothesis of an X-linked, or recessive, model of inheritance.

PMID- 7585189
TI  - Decreased alpha-secretase-cleaved amyloid precursor protein as a diagnostic
      marker for Alzheimer's disease.
AB  - The neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular
      plaques and intracellular neurofibrillary tangles. A constituent of senile
      plaques in AD is beta-amyloid, a hydrophobic peptide of 39-43 amino acids and a
      fragment of the amyloid precursor protein (APP). APP can be metabolized by at
      least two pathways, one of which involves generation of soluble APP by an
      unidentified enzyme named alpha-secretase. This cleavage generates alpha
      secretase-cleaved, soluble APP (alpha-sAPP), which in this investigation was
      measured by a new assay in cerebrospinal fluid (CSF) from members of a Swedish AD
      family with a pathogenic mutation at APP670/671 (ref. 2). Family members who
      carry the mutation and are diagnosed with AD had low levels of alpha-sAPP (160 +/
      48 ng ml-1), with no overlap compared with non-carriers (257 +/- 48 ng ml-1).
      Carriers of the presymptomatic mutation showed intermediate alpha-sAPP levels.
      Today there exists no antemortem marker in AD with sufficient sensitivity and
      specificity, but measurement of alpha-sAPP represents a new and promising
      diagnostic marker.

PMID- 7585190
TI  - Synthetic human antibodies.

PMID- 7585191
TI  - Complement-specific antibodies: designing novel anti-inflammatories.

PMID- 7585192
TI  - There's a xeno in your future.

PMID- 7585196
TI  - Euthanasia.

PMID- 7585195
TI  - Animal experimentation.

PMID- 7585197
TI  - Psychiatric artifacts.

PMID- 7585194
TI  - Androgen receptor and familial prostate cancer.

PMID- 7585193
TI  - Familial Alzheimer's chromosome 14 mutations.

PMID- 7585198
TI  - Diphtheria disaster relief.

PMID- 7585199
TI  - ApoE as a prognostic factor for post-traumatic coma.

PMID- 7585200
TI  - Keeping a lid on marijuana research.

PMID- 7585201
TI  - New global AIDS programme trying to break with the past.

PMID- 7585205
TI  - Necessary but insufficient.

PMID- 7585203
TI  - Genome sequencing projects.

PMID- 7585204
TI  - Barriers to xenotransplantation.

PMID- 7585202
TI  - The challenge of fetal gene therapy.
AB  - Three recent reports describe the first in vivo attempts at fetal gene therapy.
      The results underline the need for more intensive studies of the scientific and
      ethical implications of this new and perhaps more preventive approach to gene
      therapy.

PMID- 7585206
TI  - Genetic origins of protein shape and interaction rules.

PMID- 7585207
TI  - DNA damage, p53 and anticancer therapies.

PMID- 7585208
TI  - HIV and CD26.

PMID- 7585210
TI  - Vitamin A megatherapy for retinal abnormalities.

PMID- 7585209
TI  - Aspirin--now we can see it.

PMID- 7585211
TI  - Unpleasant pain evoked by thalamic stimulation.

PMID- 7585212
TI  - Immunomodulation to enhance gene therapy.

PMID- 7585213
TI  - Recombinant IL-12 prevents formation of blocking IgA antibodies to recombinant
      adenovirus and allows repeated gene therapy to mouse lung.
AB  - Enthusiasm for the use of recombinant adenoviruses in gene therapy has been
      tempered by the problematic immune responses that develop to the virus and virus
      infected cells. Humoral immune responses to the input viral proteins generate
      neutralizing antibodies that thwart attempts to effectively administer the
      therapy more than once. Previous studies in murine models of gene therapy for
      cystic fibrosis (CF) have shown that the formation of adenoviral antibodies of
      the IgA subtype, a process that is dependent on T helper cells of the TH2 subset,
      contributes to a block in gene transfer that occurs following a second
      administration of virus. We show in this report that coadministration of
      interferon-gamma (IFN-gamma) (or interleukin-12, which activates TH1 cells to
      secrete IFN-gamma) with the recombinant adenovirus into the airway of C57BL/6
      mice diminishes the activation of TH2 cells and formation of neutralizing
      antibody, allowing for efficient readministration of recombinant virus. This
      suggests a strategy for gene therapy of CF in which administration of a short
      acting immune modulator at the time of gene therapy may be sufficient to overcome
      the problems of humoral immunity.

PMID- 7585214
TI  - The antisense homology box: a new motif within proteins that encodes biologically
      active peptides.
AB  - Amphiphilic peptides approximately fifteen amino acids in length and their
      corresponding antisense peptides exist within protein molecules. These regions
      (termed antisense homology boxes) are separated by approximately fifty amino
      acids. Because many sense-antisense peptide pairs have been reported to recognize
      and bind to each other, antisense homology boxes may be involved in folding,
      chaperoning and oligomer formation of proteins. The antisense homology box
      derived peptide CALSVDRYRAVASW, a fragment of human endothelin A receptor, proved
      to be a specific inhibitor of endothelin peptide (ET-1) in a smooth muscle
      relaxation assay. The peptide was able to block endotoxin-induced shock in rats
      as well. Our finding of endothelin receptor inhibitor among antisense homology
      box-derived peptides indicates that searching proteins for this new motif may be
      useful in finding biologically active peptides.

PMID- 7585215
TI  - Microallelotyping defines the sequence and tempo of allelic losses at tumour
      suppressor gene loci during colorectal cancer progression.
AB  - Microallelotyping of many regions from individual colorectal tumours was used to
      determine the sequence and tempo of allelic loss on 5q, 17p and 18q during
      neoplastic progression. No allelic losses were found in normal tissues
      surrounding colorectal neoplasms, but losses occurred abruptly on 5q at the
      transition from normal colonic epithelium to the benign adenoma, and on 17p at
      the transition from adenoma to carcinoma, indicating an essential role for these
      losses in tumour progression. Allelic losses were uniform throughout extensively
      microdissected benign adenomas and carcinomas. However, substantial allelic
      heterogeneity was found in high-grade dysplasia, the transition lesion between
      adenoma and carcinoma. Thus, allelic losses on 5q and 17p are associated with
      abrupt waves of clonal neoplastic expansion, and high-grade dysplasia is
      characterized by a high degree of allelic heterogeneity.

PMID- 7585217
TI  - Long-term protection against SIV-induced disease in macaques vaccinated with a
      live attenuated HIV-2 vaccine.
AB  - The aim of this study was to test the ability of a live attenuated human
      immunodeficiency virus type 2 (HIV-2) vaccine to protect cynomolgus monkeys
      against superinfection with a pathogenic simian immunodeficiency virus (SIVsm).
      This report is an update on our previously reported observation period of nine
      months. The new data here show that three of four monkeys vaccinated with live
      HIV-2 were protected against immunosuppression and SIV-induced disease during
      more than five years of follow-up. The quality of the immunity was permissive for
      infection, but monkeys that survived showed restricted viral replication in
      peripheral blood and lymph nodes. This study shows that it is possible to induce
      protection against a pathogenic heterologous primate lentivirus and to prevent
      disease in vaccinated monkeys even if infection is not prevented. These findings
      provide evidence that protection against AIDS can be achieved by immunization.

PMID- 7585216
TI  - Stimulation in the human somatosensory thalamus can reproduce both the affective
      and sensory dimensions of previously experienced pain.
AB  - Thalamic structures involved in the unpleasant emotional or affective aspect of
      pain are poorly understood. We now describe studies of the region of the thalamic
      principal somatosensory nucleus (Vc) performed before thalamotomy for tremor in a
      patient who also had panic disorder. Microstimulation in the region posterior to
      Vc evoked chest pain, including a strong affective dimension, almost identical to
      that occurring during his panic attacks, as measured using a questionnaire.
      Results in our other patients indicate that stimulation-associated pain with a
      strong affective dimension occurred only in those patients who had previously
      experienced spontaneous pain with a strong affective component. These results are
      consistent with stimulation-evoked activation of limbic structures, which are
      connected through cortex with the region posterior to Vc and involved in the
      affective dimension of pain through conditioning by previous experience.

PMID- 7585218
TI  - CD26 expression correlates with entry, replication and cytopathicity of
      monocytotropic HIV-1 strains in a T-cell line.
AB  - Experiments to identify cell determinants involved in HIV-1 tropism revealed a
      specific decrease in the expression of the T-cell activation antigen CD26 after
      monocytotropic (M-tropic) but not T-cell line-tropic (T-tropic) virus infection
      of the PM1 T-cell line. The level of CD26 expression in single-cell clones of PM1
      correlated with the entry rate and cytopathicity of M-tropic HIV-1 variants,
      resulting in preferential survival of cells with low CD26 levels after infection.
      Experiments with recombinant viruses showed that the third hypervariable region
      of the envelope gp120 plays an important role in this selection process. This
      study identifies CD26 as a key marker for M-tropic human immunodeficiency virus
      type 1 (HIV-1) infection and suggests a mechanism for the early loss of CD26
      expressing cells in HIV-1-infected individuals.

PMID- 7585219
TI  - A picornaviral protein synthesized out of frame with the polyprotein plays a key
      role in a virus-induced immune-mediated demyelinating disease.
AB  - The DA strain and other members of the TO subgroup of Theiler's murine
      encephalomyelitis virus (TMEV) induce a chronic demyelinating disease with a
      restricted virus expression. This disease serves as an experimental model of
      multiple sclerosis; in both diseases the immune system contributes to a similar
      demyelinating pathology. Like all picornaviruses, TMEV encodes a polyprotein
      translated from one long open reading frame. The polyprotein is then processed
      into structural and non-structural viral proteins. Here, we demonstrate that the
      DA strain of TMEV has an additional alternative open reading frame that encodes a
      protein called L* that is present in infected cells. Virus with a mutation of L*
      has a dramatically decreased demyelinating activity, indicating that L* plays a
      critical role in TO subgroup-induced demyelinating disease. L* is associated with
      membranes, suggesting that L* may interact with the immune system and thereby
      mediate the viral-induced demyelinating disease.

PMID- 7585220
TI  - Release and activation of platelet latent TGF-beta in blood clots during
      dissolution with plasmin.
AB  - Transforming growth factor beta 1 (TGF-beta 1) is a platelet-derived cytokine
      involved in both normal wound healing and scarring. We show that human platelets
      contain two pools of latent TGF-beta 1, which constitute more than 95% of the
      total TGF-beta assayed in whole platelets. During clotting, one pool, the large
      latent TGF-beta complex consisting of latent TGF-beta binding protein (LTBP), the
      latency-associated peptide (LAP) and the 25-kD mature TGF-beta 1 dimer is
      released into the serum. A second pool, which contains LAP but not LTBP, is
      retained in the clot, but can be released by RGD peptide. When the clot is
      dissolved by plasmin this bound TGF-beta 1 is gradually activated and released.
      If similar mechanisms operate in vivo, the clot will act as a slow-release
      capsule of TGF-beta 1 activity during wound healing.

PMID- 7585221
TI  - Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant
      gliomas.
AB  - We have created a double mutant of the herpes simplex virus (HSV) type 1 (termed
      G207) with favourable properties for treating human malignant brain tumours:
      replication-competence in glioblastoma cells (and other dividing cells),
      attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity,
      and the presence of an easily detectable histochemical marker. G207 has deletions
      at both gamma 34.5 (RL1) loci and a lacZ gene insertion inactivating the ICP6
      gene (UL39). G207 kills human glioma cells in monolayer cultures. In nude mice
      harbouring subcutaneous or intracerebral U-87MG gliomas, intraneoplastic
      inoculation with G207 causes decreased tumour growth and/or prolonged survival.
      G207 is avirulent upon intracerebral inoculation of mice and HSV-sensitive non
      human primates. These results suggest that G207 should be considered for clinical
      evaluation in the treatment of glioblastomas.

PMID- 7585222
TI  - Identification of endothelin-1 in the pathophysiology of metastatic
      adenocarcinoma of the prostate.
AB  - Prostate cancer is the second most common cause of death from cancer in U.S. men,
      and advanced, hormone-refractory disease is characterized by painful osteoblastic
      bone metastases. Endothelin-1, more commonly known as a potent vasoconstrictor,
      is a normal ejaculate protein that also stimulates osteoblasts. We show here that
      plasma immunoreactive endothelin concentrations are significantly elevated in men
      with metastatic prostate cancer and that every human prostate cancer cell line
      tested produces endothelin-1 messenger RNA and secretes immunoreactive
      endothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and
      increases alkaline phosphatase activity in new bone formation, indicating that
      ectopic endothelin-1 may be a mediator of the osteoblastic response of bone to
      metastatic prostate cancer.

PMID- 7585224
TI  - Increased obese mRNA expression in omental fat cells from massively obese humans.
AB  - Obesity presents a significant challenge to the general health of affluent
      nations in terms of the number of people affected, the serious associated
      maladies and the lack of effective treatments. While common wisdom has held that
      obesity results from 'gluttony and sloth', a number of studies have indicated
      physiological causes of underlying the pathogenesis of obesity, with the degree
      of adiposity having a strong genetic component. Recently, the obese gene in the
      ob/ob mouse was cloned, along with its human homologue. The specific production
      of the obese protein by adipose tissue suggested that it may function in a
      feedback loop from fat tissue to the hypothalamus to control energy intake and/or
      energy expenditure, and that it may play a role in the pathogenesis of human
      obesity. In this study we report that obese mRNA expression is elevated in ex
      vivo omental adipocytes isolated from massively obese humans in the absence of an
      identifiable mutation. Therefore, we speculate that this increased expression may
      suggest that the massively obese are insensitive to the putative regulatory
      function(s) of the obese gene product.

PMID- 7585223
TI  - Overexpression of the obese (ob) gene in adipose tissue of human obese subjects.
AB  - Obesity is accompanied by complications such as hypertension, non-insulin
      dependent diabetes mellitus and atherosclerosis, which in turn cause ischaemic
      heart disease, stroke and premature death. The underlying mechanisms behind
      imbalance in energy intake and energy expenditure that lead to obesity are still
      controversial. In most populations, obesity is more common among women than men
      and is a multifactorial phenotype, which may result from a complex network of
      genetic and nongenetic factors. The relative importance of genetic factors for
      obesity is under debate. Genome searches using polymorphic markers in inbred mice
      with phenotypes that result in extreme obesity and studies of human candidate
      genes are being performed in an attempt to identify genes that contribute to
      obesity. There is evidence that body weight is physiologically regulated and it
      has been postulated that the storage of fat may provide signals to the brain that
      the body is obese, which in turn may make the subject eat less and burn more
      fuel. One of the molecules that may be involved in such signalling is the obese
      (ob) gene product. Mutations in ob result in profound obesity and type II
      diabetes in mice. The mouse ob gene and its human homologue have been cloned and
      sequenced. The gene is expressed in adipose tissue and the product has features
      of a secreted protein. We have investigated human ob expression in subcutaneous
      and omental adipose tissue obtained from non-obese and massively obese subjects
      using in situ hybridization histochemistry and report on overexpression in obese
      people.

PMID- 7585225
TI  - Resistance of microorganisms to disinfection in dental and medical devices.
AB  - The U.S. Centers for Disease Control and Prevention (CDC) recommends that only
      heat sterilization be used for all reusable devices entering the oral cavity.
      However, chemical disinfection is still employed for reprocessing dental devices
      in many areas of the world. In an analysis of a Florida dental practice
      responsible for nosocomial human immunodeficiency virus (HIV) transmissions, the
      possible role of contaminated devices was deemed unlikely in part because they
      were subjected to high-level disinfection with 2% glutaraldehyde. Disease
      transmissions have, however, been documented for endoscopes used in diagnostic
      and surgical procedures even after this treatment. In some dental devices,
      lubricants mix with potentially infectious patient materials, and organic debris
      has been observed in endoscopes after cleaning. We have investigated whether
      lubricants can render high-level chemical disinfection procedures ineffective and
      have addressed the role that some common devices may play in disease
      transmission. We report here that HIV in whole-blood samples and Pseudomonas
      aeruginosa in blood and plasma survived high-level disinfection when entrapped in
      lubricants used in dental handpieces and endoscopes. We also found that
      lubricated dental devices used to clean and polish teeth (prophylaxis angles)
      have the potential to transfer sufficient amounts of blood to infect human
      lymphocyte cultures with HIV. These results emphasize the need to subject
      reusable dental devices to a heat-sterilization protocol that penetrates the
      lubricant.

PMID- 7585227
TI  - Complement inhibitory therapeutics and xenotransplantation.
AB  - Once complement-mediated HAR has been inhibited, the full spectrum of cellular
      and antibody-mediated inflammatory and immune responses characteristic of acute
      and chronic rejection will need to be counter-manded. But the fact remains that
      if xenotransplantation is to become a clinical reality, a clinically relevant
      means of inhibiting complement activation will be required. Soluble complement
      receptor type 1 provides such a therapeutic option and an option where the dosing
      regimen is under the control of the physician and can be adjusted in response to
      the needs of the patient.

PMID- 7585228
TI  - Tolerance and xenograft survival.

PMID- 7585226
TI  - The generation of transgenic pigs as potential organ donors for humans.

PMID- 7585230
TI  - World blindness data.

PMID- 7585229
TI  - Optical biopsy and imaging using optical coherence tomography.
AB  - Optical coherence tomography is a new imaging technique that can perform high
      resolution, micrometre-scale, cross-sectional imaging in biological systems. The
      technology has been developed, and reduced to, preliminary clinical practice in
      ophthalmology. The challenging problem that OCT may address is the development of
      'optical biopsy' techniques. These techniques can provide diagnostic imaging of
      tissue morphology without the need for excision of specimens. Many investigations
      remain to identify optimal areas for clinical application, and additional
      engineering must be done to integrate vertically the technology and to reduce it
      to clinical practice. Nevertheless, preliminary studies indicate the feasibility
      of developing this technology for a wide range of clinical and research
      diagnostic imaging applications. The ability to non-excisionally evaluate tissue
      morphology using a catheter or an endoscope could have a significant impact on
      the diagnosis and management of a wide range of diseases.

PMID- 7585232
TI  - Percentage scattergram to depict changes in large amounts of data over time.
AB  - Graphical representation of changes in epidemiologic or clinical parameters over
      time is difficult when a large amount of data is involved. The traditional
      methods either cannot incorporate all necessary information (bar graphs, pie
      charts, tables) or are unable to depict information on more than a limited number
      of individuals (scattergrams). We have designed an effective way of visual
      presentation of the changes a variable demonstrates over time. The percentage
      scattergram provides accurate and complete depiction of any number of data
      points, allowing comprehensive and rapid analysis.

PMID- 7585231
TI  - Vision screening of preschool children in Italy.
AB  - Vision screening of preschool children is designed and performed to identify
      those affected by amblyopia or related, predisposing visual defects. In order to
      determine the prevalence of preschool vision screening in Italy, a questionnaire
      was mailed to the 635 regional health offices in which the country's national
      health system was organized at the time of the study. Results of this survey
      demonstrated that in 61.3% of the regions which responded, some form of preschool
      vision screening is performed. However, individual, non-standardized methods are
      used by the physicians or health care professionals responsible in each regional
      program. It is evident from this study that standardized procedures for preschool
      vision testing are lacking in Italy, and that the existing European Community
      guidelines should be disseminated and applied on a greater scale for the
      development of such a program on the national and European level.

PMID- 7585235
TI  - Changes of the eye caused by the climate in Rwanda, Africa.
AB  - Rwanda is a small but densely populated country, situated at the watershed
      between East and West Africa, close to the equator. The mean elevation is around
      1500 m. We studied 114 males (mean age 28.42 years) and 111 females (mean age
      29.84 years) at the ophthalmological outpatient department of the Centre
      Hospitalier in Kigali. Changes to the eye caused by the climate were fewer than
      expected. Only 10 patients (5 males, 5 females) with pterygium (mean age 33.0
      years), and four males and two females with climatic droplet keratopathy (mean
      age 47.5 years) were observed. However, the size of the pinguecula was marked.
      Corneal thickness, measured with Haag-Streit's device, averaged 0.524 mm in 38
      males and 0.521 mm in 38 females. The Rwandans showed a normal chamber depth, a
      mean of 2.98 mm being noted in 107 males and a mean of 2.80 mm in 106 females.

PMID- 7585233
TI  - Older-onset diabetes and lens opacities. The Beaver Dam Eye Study.
AB  - PURPOSE: To determine the prevalence of lens opacities in older-onset diabetic
      persons. METHODS: A study of age-related eye disease in a population (n = 4926)
      of adults in Beaver Dam, Wisconsin. Study participants were examined and
      interviewed according to protocol. Photographs were taken of the lenses of both
      eyes of all study participants. Photographs were graded in a standard fashion.
      Diabetes was defined by history, doctors' records and serum glucose criteria.
      RESULTS: Persons who were diabetic were significantly more likely to have
      cortical lens opacities (age-adjusted odds ratio 1.72, 95% CI 1.29-2.30 for right
      eyes) and were more likely to have previously undergone cataract surgery (age
      adjusted odds ratio 2.01, 95% CI 1.43-2.82 for either eye) than people without
      diabetes. Longer duration of diabetes significantly increased the odds of having
      cortical opacity. CONCLUSION: Older-onset diabetes is associated with increased
      frequency of a specific age-related lens change, cortical opacity. It is also
      associated with increased frequency of cataract surgery.

PMID- 7585236
TI  - Eradication of blindness secondary to diabetic retinopathy.

PMID- 7585234
TI  - Available data on blindness (update 1994)

PMID- 7585237
TI  - Validation of methods for the assessment of cataract progression in the Roche
      European-American Anticataract Trial (REACT)
AB  - The Roche European-American Anticataract Trial (REACT) will assess the effect of
      antioxidants on progression of cataract in humans. This report evaluates the
      methods used in REACT. Seventy three subjects (139 eyes) with cortical (C),
      posterior subcapsular (P), nuclear (N) or mixed cataract were seen twice within
      two weeks for eye examinations, assessments of visual function, lens photographs
      and CCD images. The degree of cataract and nuclear color (NC) were assessed with
      subjective (LOCS III) and objective (computerized, CASE 2000 CCD) methods. Repeat
      visit values were used to calculate intraclass correlation coefficients (r1) and
      95% tolerance limits (TL). A clinically significant change (CSC) was defined as
      one step in LOCS III. The relative power of each method to detect cataract change
      and sample sizes needed to achieve statistically significant results were
      calculated. The r1 values for visual function tests ranged from 0.76 to 0.88; if
      these tests of visual function were used to detect a clinically significant
      change in cataract severity, sample sizes of 840 to 2707 per group would be
      needed. The r1 values for LOCS III were 0.88 to 0.97, and sample sizes ranged
      from 50 to 135 per group. The r1 values for the CCD were 0.93 to 0.98, and sample
      sizes ranged from 1 to 42 with poorer values relating to measurement of P. We
      conclude that the methods used in REACT are reproducible. The analytical
      algorithms in the image analysis programs did not permit differentiation between
      C and P opacification; therefore, P cataract is best measured with LOCS III.
      REACT sample sizes are adequate to detect a difference of 0.2 LOCS III units/year
      between the mean rates of cataract progression in two groups.

PMID- 7585238
TI  - Causes of childhood blindness in east Africa: results in 491 pupils attending 17
      schools for the blind in Malawi, Kenya and Uganda.
AB  - Pupils attending 12 schools for the blind in Malawi, 3 schools in Kenya and 2
      schools in Uganda were examined to determine the causes of severe visual
      impairment or blindness (visual acuity in the better eye of less than 6/60). A
      total of 491 pupils aged 3-22 years was examined. Visual acuity was measured in
      each eye using a Snellen E chart. The anatomical site of abnormality and
      underlying cause of visual loss were determined by clinical examination for each
      eye, and for the child. Information was recorded on a standard reporting form
      (the WHO/PBL Eye Examination Record for Children with Blindness and Low Vision).
      Data were analysed for those aged less than 16 years using a database which
      accompanies the form. Preventable and treatable causes were identified. 260
      pupils aged 5-20 years were examined in Malawi, 163 pupils aged 3-19 years were
      examined in Kenya and 68 pupils aged 6-22 years were examined in Uganda. Of the
      491 students included in the study 309 (62.9%) were blind (BL) and 69 (14.1%)
      were severely visually impaired (SVI). 244 were aged less than 16 years and had
      SVI/BL. In these 244 children 35.2% of visual loss was due to corneal pathology,
      13.5% was due to cataract and 14.8% to diseases of the retina. Corneal pathology,
      attributed to vitamin A deficiency and measles infection in the majority, was
      responsible for proportionally more SVI/BL in students in Malawi than in Uganda
      or Kenya.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585239
TI  - Patterns of diabetic eye care by primary care physicians in the state of Indiana.
AB  - Diabetic retinopathy is the leading cause of new blindness in the 20 to 74-age
      group in the United States. The American Academy of Ophthalmology (AAO) and
      American Diabetes Association (ADA) have recommended guidelines for eye
      examination to assist primary care physicians in managing these patients. The
      purpose of this study is to investigate the patterns of diabetic eye care offered
      by primary care physicians in the State of Indiana. A survey questionnaire was
      sent to 1279 primary care physicians in central Indiana. Of those surveyed, 259
      (20%) responded. Thirty-five percent of respondents stated that they never refer
      patients for ocular examination while 26% refer all patients. The remainder refer
      on a case-by-case basis. Patients who are not referred have their fundus examined
      only 70% of the time by the primary care physician and 96% of these examinations
      are performed with an undilated pupil. When referred, 20% of Type I patients are
      referred at the time of diagnosis and 50% by one year. Of the Type II patients,
      only 2% are referred at the time of diagnosis and 70% by one year.
      Ophthalmologists receive 75% of the referrals while optometrists receive 20%. Our
      results show that a significant number of primary care physicians in the State of
      Indiana do not follow the recommended guidelines set forth for diabetic eye care.

PMID- 7585240
TI  - Patterns of referral and examination for retinopathy in pregnant women with
      diabetes by primary care physicians.
AB  - PURPOSE: Family practice (FP), General Practice (GP) and obstetrics-gynecology
      (OB/GYN) physicians were surveyed to determine whether they routinely referred
      pregnant patients with diabetes to an ophthalmologist, looked into the patient's
      eyes to screen for retinopathy, and dilated the eyes for fundi examination.
      METHODS: Hospitals providing obstetrical services were contacted to identify
      primary-care physicians. Physicians identified as having obstetrical privileges
      were surveyed by mail to determine if they were actively providing obstetrical
      care. Physicians who provided both obstetrical and diabetes care were mailed a
      survey. RESULTS: Of 668 physicians surveyed, 429 responded: 224 FPS, 184 OB/GYNS
      and 21 GPS. A relatively small percentage (27%) of physicians in both groups
      routinely refer all of their pregnant patients with pre-existing diabetes to an
      ophthalmologist. Family practice physicians were more likely to perform an eye
      exam to screen for retinopathy in patients with both pre-existing and gestational
      diabetes than OB/GYNS (p < .0005). Only 11% of FPS and no OB/GYNS reported that
      they dilated the eyes when performing a fundus examination (p = .04). CONCLUSION:
      The physicians surveyed under-utilize recommended strategies for eye care of
      pregnant women with pre-existing diabetes. Based upon these results, we call for
      a recommitment to partnership of primary-care physicians and ophthalmologists in
      the detection and treatment of diabetic retinopathy during pregnancy.

PMID- 7585242
TI  - An element in human U6 RNA destabilizes the U4/U6 spliceosomal RNA complex.
AB  - Large-scale changes in RNA secondary structure, such as those that occur in some
      of the spliceosomal RNAs during pre-mRNA splicing, have been proposed to be
      catalyzed by ATP-dependent RNA helicases. Here we show that deproteinized human
      U4/U6 spliceosomal RNA complex, which has the potential for extensive
      intermolecular base pairing, contains a cis-acting element that promotes its
      dissociation into free U4 and U6 RNAs. The destabilzing element corresponds to
      the bae of putative intramolecular stem in U6 RNA that includes the 3' three
      quarters of the molecule. Oligonucleotides expected to compete for U6 RNA 3' stem
      formation promote assembly of the human U4/U6 RNA complex under conditions that
      otherwise result in dissociation of the U4/U6 complex. Truncation of the putative
      3' stem-forming sequences in U6 RNA by oligonucleotide-directed RNase H cleavage
      increases the melting temperature of the U4/U6 RNA complex by almost 20 degree C,
      to a level commensurate with its intermolecular base-pairing potential. We
      conclude that the stability of the competing human U6 RNA intramolecular 3' stem,
      combined with a low activation energy for conformational rearrangement, causes
      the human U4/U6 RNA complex to be intrinsically unstable despite its base-pairing
      potential. Therefore a helicase activity may not be necessary for disassembly of
      the human U4/U6 complex during activation of the spliceosome. We propose that a
      previously identified base-pairing interaction between U6 and U2 RNAs may
      stabilize the human U4/U6 RNA complex by antagonizing U6 RNA 3' stem formation.

PMID- 7585243
TI  - Specificity of Prp24 binding to RNA: a role for Prp24 in the dynamic interaction
      of U4 and U6 snRNAs.
AB  - Prp24 was previously isolated as a suppressor of a cold-sensitive U4 mutation and
      is required for at least the first step of splicing in vitro. Our investigation
      of the in vitro RNA binding properties of the purified Prp24 protein shows that
      it binds preferentially to the U4/U6 hybrid snRNAs compared to other snRNAs. The
      interaction between Prp24 and the U4/U6 hybrid appears to involve two regions in
      the RNA: the 39-57 region of U6 and stem II of the U4/U6 hybrid. Interestingly,
      some U4 mutations, which destabilize stem II, increase the affinity of Prp24 for
      the U4/U6 RNAs compared to the wild type. This suggests that the binding of Prp24
      to the U4/U6 RNAs may involve some destabilization of the RNA duplex. We also
      found that Prp24 can stimulate the annealing of U4 and U6, suggesting that Prp24
      participates in both the formation and disassembly of the U4/U6 hybrid during
      splicing.

PMID- 7585244
TI  - Analysis of the role of the pseudoknot component in the SRV-1 gag-pro ribosomal
      frameshift signal: loop lengths and stability of the stem regions.
AB  - The simian retrovirus-1 (SRV-1) gag-pro frameshift signal was identified in
      previous work, and the overall structure of the pseudoknot involved was confirmed
      (ten Dam E, Brierley I, Inglis S, Pleij C, 1994, Nucleic Acids Res 22:2304-2310).
      Here we report on the importance of specific elements within the pseudoknot. Some
      mutations in stem S1 that maintain base pairing have reduced frameshift
      efficiencies. This indicates that base pairing in itself is not sufficient. In
      contrast, frameshifting correlates qualitatively with the calculated stability of
      mutations in S2. The stems thus play different roles in the frameshift event. The
      nature of the base in L1 has little influence on frameshift efficiency. It is
      however required to bridge S2; deleting it lowers frameshifting from 23 to 9%. In
      L2, frameshift efficiency was not affected in a mutant that changed 10 to 12
      bases. This makes it unlikely that the primary sequence of L2 plays a role in -1
      frameshifting, in contrast to readthrough in Moloney murine leukemia virus (Wills
      N, Gesteland R, Atkins J, 1994, EMBO J 13:4137-4144). Deletions of 2 and 3 bases
      gave more frameshifting than the wild type, probably reflecting the increased
      stability of the pseudoknot due to a shorter loop L2. Deleting even more bases
      reduces frameshifting compared to wild-type levels. At this point, stress will
      build up in L2, and this will reduce overall pseudoknot stability.

PMID- 7585245
TI  - Differential regulation of two related RNA-binding proteins, iron regulatory
      protein (IRP) and IRPB.
AB  - The iron regulatory protein (IRP) is a cytoplasmic RNA-binding protein that
      regulates cellular iron metabolism at the posttranscriptional level. IRP is an
      unusual bifunctional molecule: in iron-replete cells it predominantly exists as a
      4Fe-4S protein and exhibits aconitase enzymatic activity, whereas apo-IRP
      prevails in iron-starved cells and binds to iron-responsive elements (IREs),
      structural motifs within the untranslated regions of mRNAs involved in iron
      metabolism. A related protein with iron-regulated IRE-binding activity, IRPB, was
      previously identified in rodent cells. IRE-binding by IRP and IRPB is induced by
      iron deprivation and nitric oxide (NO). Controversial hypotheses have proposed
      that the induction of IRE-binding activity by iron results either from de novo
      synthesis of the apo-protein or from a posttranslational conversion of the Fe-S
      to the apo-protein form. This prompted a detailed analysis of how iron and NO
      regulate the RNA-binding activities of IRP and IRPB. We demonstrate that IRP is a
      relatively stable protein (half-life > 12 h). The induction of IRE-binding does
      not require de novo protein synthesis but results from conversion of Fe-S IRP to
      apo-IRP. In contrast, IRPB appears less stable in nonstarved cells (half-life
      approximately 4-6 h) and must be synthesized de novo following iron starvation.
      Our results furthermore reveal that two RNA-binding proteins with close
      structural and functional similarities that respond to the same cellular signals
      are regulated by predominantly different mechanisms.

PMID- 7585241
TI  - Reliability of visual acuity measurements and screening under field conditions.
AB  - PURPOSE: The purpose of this analysis was to investigate the reliability of
      visual acuity screening and measurements made under field conditions when
      standardization of all test conditions is not possible. SETTING AND METHODS: In
      the Washington County Follow-Up Eye Study conducted in 1985 among cases of ocular
      histoplasmosis and controls from the same community who had been selected in
      1970, a primary goal was to obtain a current visual acuity measurement of each
      eye of each participant in order to assess 15-year changes in visual acuity. Both
      visual acuity screening and measurement were accomplished on two separate
      occasions and in two separate locations (home or workplace and clinic) for 308
      eyes and 317 eyes, respectively, of 161 participants. Screening was used to
      classify the visual acuity as 20/40 or better, worse than 20/40 but at least
      20/160, or worse than 20/160. Screening and measurement were accomplished on at
      least one occasion for the eyes of 192 of 216 eligible individuals. RESULTS:
      Among 308 eyes screened twice, 289 (94%) were classified identically (kappa =
      0.80). Among 317 eyes with visual acuity measured on two occasions, the
      measurements were within two lines for 305 eyes (96%; kappa = 0.50). Among eyes
      for which classifications of visual acuity from screening and measurement could
      be compared, 325 (96%) of 340 assessed at home and 326 (96%) of 338 assessed in
      clinic were classified in the same way (kappa = 0.86 and 0.88, respectively).
      CONCLUSION: Despite the unavoidable lack of standardization of test conditions
      when visual acuity was screened and measured in the home or work-place, the
      results were highly reliable when compared with visual acuity testing in the
      clinic under standard conditions.

PMID- 7585247
TI  - Isolation and characterization of a novel, low abundance hnRNP protein: A0.
AB  - Pre-messenger RNA is bound by a variety of proteins to form large heterogeneous
      nuclear ribonucleoprotein (hnRNP) complexes. As defined by immunoprecipitation
      and two-dimensional gel electrophoresis, there appear to be more than 20 abundant
      hnRNP proteins ranging in size from 34 kDa to 120 kDa. One major class, the A/B
      family, is typified by its characteristic primary structure containing two RNA
      binding domains followed by a glycine-rich C-terminus. We report the cloning and
      characterization of a novel, low-abundance member of the A/B family named hnRNP
      A0. This protein was affinity isolated using a biotinylated RNA probe [G4(AU3)4A]
      designed to select a 32-kDa protein implicated in mRNA stability in mammalian
      cells. hnRNP A0 is a basic protein with a predicted mass of 31.7 kDa and an
      isoelectric point of 10.1. Comparative protease mapping shows that it is not the
      AUUUA binding protein we intended to clone. A0 is present in hnRNP complexes and
      is encoded by a gene distinct from that of any previously cloned A/B family
      member.

PMID- 7585246
TI  - SL1 trans-splicing specified by AU-rich synthetic RNA inserted at the 5' end of
      Caenorhabditis elegans pre-mRNA.
AB  - In Caenorhabditis elegans, pre-mRNAs of many genes are trans-spliced to one of
      two spliced leaders, SL1 or SL2. Some of those that receive exclusively SL1 have
      been characterized as having at their 5' ends outrons, AU-rich sequences similar
      to introns followed by conventional 3' splice sites. Comparison of outrons from
      many different SL1-specific C. elegans genes has not revealed the presence of any
      consensus sequence that might encode SL1-specificity. In order to determine what
      parameters influence the splicing of SL1, we performed in vivo experiments with
      synthetic splice sites. Synthetic AU-rich RNA, 51 nt or longer, placed upstream
      of a consensus 3' splice site resulted in efficient trans-splicing. With all
      sequences tested, this trans-splicing was specifically to SL1. Thus, no
      information beyond the presence of AU-rich RNA at least as long as the minimum
      length C. elegans intron, followed by a 3' splice site, is required to specify
      trans-splicing or for strict SL1 specificity.

PMID- 7585248
TI  - Enhanced self-splicing of Physarum polycephalum intron 3 by a second group I
      intron.
AB  - The third group I intron of Physarum polycephalum is found at the same site in
      the large subunit rRNA as the well-characterized intron from Tetrahymena
      thermophila. Formation of alternative structures in the rRNA can inhibit self
      splicing of the Tetrahymena intron. We report that splicing of Physarum intron 3
      is also influenced by adjacent sequences. In this case, however, splicing is
      stimulated by the presence of a second group I intron 24 nucleotides downstream.
      In vitro, intron 3 self-splices 10-25-fold faster in transcripts containing both
      introns. In vivo, intron 3 is excised from pre-rRNA before intron 2 in the
      majority of transcripts, as judged by PCR amplification of processing
      intermediates. This is an unusual example in which self-splicing is enhanced by
      the juxtaposition of two group I introns. This cooperative effect may be mediated
      by a conformational change in the rRNA.

PMID- 7585249
TI  - Hydroxyl radical footprinting of ribosomal proteins on 16S rRNA.
AB  - Complexes between 16S rRNA and purified ribosomal proteins, either singly or in
      combination, were assembled in vitro and probed with hydroxyl radicals generated
      from free Fe(II)-EDTA. The broad specificity of hydroxyl radicals for attack at
      the ribose moiety in both single- and double-stranded contexts permitted probing
      of nearly all of the nucleotides in the 16S rRNA chain. Specific protection of
      localized regions of the RNA was observed in response to assembly of most of the
      ribosomal proteins. The locations of the protected regions were in good general
      agreement with the footprints previously reported for base-specific chemical
      probes, and with sites of RNA-protein crosslinking. New information was obtained
      about interaction of ribosomal proteins with 16S rRNA, especially with helical
      elements of the RNA. In some cases, 5' or 3' stagger in the protection pattern on
      complementary strands suggests interaction of proteins with the major or minor
      groove, respectively, of the RNA. These results reinforce and extend previous
      data on the localization of ribosomal proteins with respect to structural
      features of 16S rRNA, and offer many new constraints for three-dimensional
      modeling of the 30S ribosomal subunit.

PMID- 7585250
TI  - Identification of phosphates involved in catalysis by the ribozyme RNase P RNA.
AB  - The RNA subunit of ribonuclease P (RNase P RNA) is a catalytic RNA that cleaves
      precursor tRNAs to generate mature tRNA 5' ends. Little is known concerning the
      identity and arrangement of functional groups that constitute the active site of
      this ribozyme. We have used an RNase P RNA-substrate conjugate that undergoes
      rapid, accurate, and efficient self-cleavage in vitro to probe, by
      phosphorothioate modification-interference, functional groups required for
      catalysis. We identify four phosphate oxygens where substitution by sulfur
      significantly reduces the catalytic rate (50-200-fold). Interference at one site
      was partially rescued in the presence of manganese, suggesting a direct
      involvement in binding divalent metal ion cofactors required for catalysis. All
      sites are located in conserved sequence and secondary structure, and positioned
      adjacent to the substrate phosphate in a tertiary structure model of the ribozyme
      substrate complex. The spatial arrangement of phosphorothioate-sensitive sites in
      RNase P RNA was found to resemble the distribution of analogous positions in the
      secondary and potential tertiary structures of other large catalytic RNAs.

PMID- 7585251
TI  - GNRA tetraloops make a U-turn.
AB  - The U-turn (uridine turn) is an RNA structural motif that contains a change in
      backbone direction stabilized by specific interactions across the bend. It was
      first identified in the anticodon loop and the T-loop of yeast tRNA(Phe) (Quigley
      & Rich, 1976, Science 194:796-806) and has recently also been found in the
      crystal structure of the hammerhead ribozyme (Pley HW, Flaherty KM, McKay DB,
      1994a, Nature 372:68-74). These U-turn motifs follow a UNR consensus sequence
      (where N is any nucleotide and R is G or A). Here we report that the frequently
      occurring GNRA tetraloops also contain a U-turn motif, and we discuss the role of
      U-turns as abundant tertiary structural motifs in RNA.

PMID- 7585252
TI  - The superfamily of arginine/serine-rich splicing factors.

PMID- 7585253
TI  - Accurate and efficient insertional RNA editing in isolated Physarum mitochondria.
AB  - RNA editing is a process whereby nucleotide insertion, deletion, or base
      substitution results in the production of an RNA whose sequence differs from that
      of its template. The mitochondrial RNAs of Physarum polycephalum are processed
      specifically at multiple sites by both mono- and dinucleotide insertions, as well
      as apparent cytidine (C) to uridine (U) changes. The precise mechanism and timing
      of these processing events are currently unknown. We describe here the
      development of an isolated mitochondrial system in which exogenously supplied
      nucleotides can be incorporated into RNAs under defined conditions. The results
      of S1 nuclease protection, nearest neighbor and RNase T1 fingerprint analyses
      indicate that the vast majority of these newly synthesized mitochondrial RNAs
      have been accurately and efficiently processed by both mono- and dinucleotide
      insertions. This work provides a direct demonstration of faithful nucleotide
      insertion in a mitochondrial editing system. In contrast, the newly synthesized
      RNAs are not processed by C to U changes in the isolated mitochondria, suggesting
      that the base changes observed in Physarum are unlikely to occur via a
      deletion/insertion mechanism.

PMID- 7585254
TI  - SR proteins escort the U4/U6.U5 tri-snRNP to the spliceosome.
AB  - Pre-spliceosomes, formed in HeLa nuclear extracts and isolated by sedimentation
      on glycerol gradients, were chased into spliceosomes, the macromolecular enzyme
      that catalyzes intron removal. We demonstrate that the pre-spliceosome to
      spliceosome transition was dependent on ATP hydrolysis and required both a U-rich
      small nuclear ribonucleoprotein (U snRNP)-containing fraction and a fraction of
      non-snRNP factors. The active components in the non-snRNP fraction were
      identified as SR proteins and were purified to apparent homogeneity. Recombinant
      SR proteins (ASF, SC35, SRp55), as well as gel-purified SR proteins, with the
      exception of SRp20, were able to restore efficient spliceosome formation. We also
      demonstrate that the pre-spliceosome to spliceosome transition requires
      phosphorylated SR proteins. This is the first evidence that SR proteins are
      required for the pre-spliceosome to spliceosome transition, the step at which the
      U4/U6.U5 tri-snRNP assembles on the pre-mRNA. The results shown here, together
      with previous data, suggest U snRNPs require SR proteins as escorts to enter the
      assembling spliceosome.

PMID- 7585255
TI  - Evidence for a conserved relationship between an acceptor stem and a tRNA for
      aminoacylation.
AB  - The anticodon-independent aminoacylation of RNA hairpin helices that reconstruct
      tRNA acceptor stems has been demonstrated for at least 10 aminoacyl-tRNA
      synthetases. For Escherichia coli cysteine tRNA synthetase, the specificity of
      aminoacylation of the acceptor stem is determined by the U73 nucleotide adjacent
      to the amino acid attachment site. Because U73 is present in all known cysteine
      tRNAs, we investigated the ability of the E. coli cystein enzyme to aminoacylate
      a heterologous acceptor stem. We show here that a minihelixCys based on the
      acceptor-T psi C stem of yeast tRNACys is a substrate for the E. coli enzyme, and
      that aminoacylation of this minihelix is dependent on U73. Additionally, we
      identify two base pairs in the acceptor stem that quantitatively convert the E.
      coli acceptor stem to the yeast acceptor stem. The influence of U73 and these two
      base pairs is completely retained in the full-length tRNA. This suggests a
      conserved relationship between the acceptor stem alone and the acceptor stem in
      the context of a tRNA for aminoacylation with cysteine. However, the primary
      determinant in the species-specific aminoacylation of the E. coli and yeast
      cysteine tRNAs is a tertiary base pair at position 15:48 outside of the acceptor
      stem. Although E. coli tRNACys has an unusual G15:G48 tertiary base pair, yeast
      tRNACys has a more common G15:C48 that prevents efficient aminoacylation of yeast
      tRNACys by the E. coli enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585256
TI  - Most mRNAs in the nematode Ascaris lumbricoides are trans-spliced: a role for
      spliced leader addition in translational efficiency.
AB  - Some pre-mRNAs in nematodes are processed by trans-splicing. In this reaction, a
      22-nt 5' terminal exon (the spliced leader, SL) and its associated 2,2,7
      trimethylguanosine cap are acquired from a specialized Sm snRNP, the SL RNP.
      Although it has been evident for many years that not all nematode mRNAs contain
      the SL sequence, the prevalence of trans-spliced mRNAs has, with the exception of
      Caenorhabditis elegans, not been determined. To address this question in an
      organism amenable to biochemical analysis, we have prepared a message-dependent
      protein synthesis system from developing embryos of the parasitic nematode,
      Ascaris lumbricoides. Using this system, we have used both hybrid-arrest and
      hybrid-selection approaches to show that the vast majority (80-90%) of A.
      lumbricoides mRNAs contain the SL sequence and therefore are processed by trans
      splicing. Furthermore, to examine the effect of SL addition on translation, we
      have measured levels of protein synthesis in extracts programmed with a variety
      of synthetic mRNAs. We find that the SL sequence itself and its associated
      hypermethylated cap functionally collaborate to enhance translational efficiency,
      presumably at the level of initiation of protein synthesis. These results
      indicate that trans-splicing plays a larger role in nematode gene expression than
      previously suspected.

PMID- 7585258
TI  - Characterization of multiple circular RNAs derived from a plant viroid-like RNA
      by sequence deletions and duplications.
AB  - Northern blot hybridizations with a probe complementary to a 275-nt circular RNA
      isolated from carnation plants revealed that this RNA co-exists in vivo with
      minor amounts of other small circular RNAs. Sequencing of cDNA clones of nine RNA
      species demonstrated deletions and duplications of the predominant 275-nt RNA.
      Minor sequence heterogeneities were observed at the crossover sites. Deletions
      mapped to three arms of the cruciform structure of lowest free energy obtained
      previously for the parental 275-nt RNA, whereas repeats encompassed mostly
      regions of the arm where deletions were not found. Some of the deleted and
      duplicated regions corresponded to sequences forming part of the two hammerhead
      structures involved in the in vitro self-cleavage of the plus and minus strands
      of the 275-nt RNA. A copy choice model is proposed for the emergence of deletions
      and duplications, where the RNA polymerase with the nascent strand dissociates
      from the template at regions rich in secondary and possibly tertiary structures,
      and reinitiates synthesis at different upstream and downstream positions.

PMID- 7585257
TI  - Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry.
AB  - Protein complexes assembled on mRNA precursors can be separated by gel filtration
      chromatography to yield spliceosomal and H complex fractions (Reed R, Griffith J,
      Maniatis T, 1988, Cell 53:949-961; Reed R, 1990, Proc Natl Acad Sci USA 87:8031
      8035.). Here we use Nano electrospray mass spectrometry (Wilm M, Mann M, 1994,
      Int J Mass Spectrometry Ion Processes 136:167-180) to identify proteins complexed
      with Adeno-pre-mRNA in the H complex peak. Four of the major hnRNP proteins, A1,
      B1, C1, and G, were identified by database analysis based on peptide mass and
      sequence information. A fifth protein in the H complex peak, corresponding to
      hnRNP P2, is shown to be the product of the TLS/FUS gene. This was originally
      identified as a chimeric oncogene formed by the chromosome translocation t(12;16)
      that is responsible for myxoid liposarcoma. The involvement of hnRNP P2 in
      oncogenesis provides a clear example of the importance of hnRNP proteins in
      molecular disease.

PMID- 7585260
TI  - Infection control.

PMID- 7585261
TI  - Infection control.

PMID- 7585259
TI  - Competition between ribosome and SecA binding promotes Escherichia coli secA
      translational regulation.
AB  - SecA protein, the protein translocation ATPase of Escherichia coli, autogenously
      regulates its translation during normal protein secretion by binding to a
      secretion-responsive element located near the 5' end of its gene on geneX-secA
      mRNA. In order to characterize this autoregulation further, RNA footprinting and
      primerextension inhibition (toeprinting) studies were carried out with a segment
      of geneX-secA RNA, 30S ribosomal subunits and tRNAfMet along with purified SecA
      protein. The results show that ribosome and SecA-binding sites overlap,
      indicating that a simple competition for binding of geneX-secA mRNA presumably
      governs the translation initiation step. Further analysis showed that SecA
      protein was able to specifically dissociate a preformed 30S-tRNAfMet-geneX-secA
      RNA ternary complex as indicated by the disappearance of its characteristic
      toeprint after SecA addition. These findings are consistent with secA
      autoregulation, and they suggest a novel mechanism for the autoregulatory
      behavior of this complex protein.

PMID- 7585263
TI  - Office overhead expense insurance: understanding the sometimes "misunderstood"
      plan.

PMID- 7585264
TI  - Creating value for your patients.

PMID- 7585262
TI  - Uncommon postoperative temporomandibular joint complications.

PMID- 7585265
TI  - PSR offers quick, easy periodontal screening.

PMID- 7585266
TI  - Detection of premalignant oral lesions: a 10 year retrospective study in Alberta.
AB  - A comprehensive review of all oral premalignant lesions and squamous cell
      carcinomas (SCC) diagnosed and biopsied by the oral pathology diagnostic service
      at the University of Alberta over two sequential five-year periods (1984-1988 and
      1989-1993) was undertaken. There was a disproportionate increase in the number of
      premalignant biopsies conducted in 1989-93 relative to the number of SCC
      biopsies, suggesting an improvement in the detection of oral pre-malignancy by
      dentists.

PMID- 7585267
TI  - Human bites to the hand.
AB  - Human bites to the hand or penetrating injuries contaminated with saliva can be a
      source of aggressive infection and debilitating injury. These types of injuries
      may also be a mode for the transmission of disease, notably hepatitis B. Dental
      personnel have an increased risk of experiencing bite injuries and should
      understand the general principles of appropriate management. Staphylococcal or
      streptococcal species are often associated with infected bite injuries, and
      amoxicillin and clavulanate are currently advised for prophylaxis. Wound
      cleansing and careful monitoring, combined with appropriate prophylaxis, are the
      mainstays of treatment.

PMID- 7585269
TI  - Cancer of the tongue.
AB  - Squamous cell carcinoma of the tongue is the most common intraoral malignancy. It
      may be preceded by visible precursor lesions showing hyperkeratosis,
      erythroplakia or a combination of these conditions. The clinical appearance is
      highly variable, and ranges from asymptomatic white patches to large fungating,
      infiltrating lesions. Earlier detection of squamous cell carcinoma of the tongue
      should improve survival rates for this malignancy, which have not appreciably
      increased over the past several decades. The oral cavity is an accessible site
      and the dentist has an important role to play in early detection.

PMID- 7585268
TI  - The use of diagnostic tests to aid clinical diagnosis.
AB  - Clinical decision making in dentistry involves some uncertainty and error, but in
      the absence of good clinical research it is often more of an art than a science.
      This article demonstrates a way in which clinicians can consistently and
      effectively base the diagnostic process on scientific evidence. The authors
      examine the selection and utility of supplemental diagnostic tests, describe the
      properties of these tests, and explain how test results can be used to augment
      clinical opinion. To aid the dental clinician in the decision making process, a
      step-by-step strategy is presented for the detection of squamous cell carcinoma
      using toluidine blue dye.

PMID- 7585272
TI  - The globalization of heart research. Reflections on the XVth World Congress of
      the International Society for Heart Research, Prague 1995.

PMID- 7585271
TI  - [Benign migratory glossitis: an enigmatic lesion].
AB  - Although benign migratory glossitis, commonly called "geographic tongue," is
      frequently observed, we still have not been able to determine its etiology. While
      the condition is usually asymptomatic, the spectacular appearance of the lesion
      frequently causes the patient considerable worry. Based on a review of the
      literature, different theories on the lesion's etiology as well as therapeutic
      modalities will be discussed.

PMID- 7585270
TI  - Verrucous carcinoma of the mouth.
AB  - Verrucous carcinoma is a slow-growing, well differentiated carcinoma that is
      chiefly exophytic but can invade and destroy oral tissues. It typically presents
      as an extensive, white, warty lesion of the buccal mucosa or mandibular gingiva,
      although it also occurs at other sites. Diagnosis can be difficult, with repeat
      biopsies being needed in some cases. The persistent nature of the condition can
      make management difficult and the possibility of recurrent disease is high.

PMID- 7585273
TI  - Role of stress concentration in the pathogenesis of cardiac rupture following
      acute myocardial infarction.
AB  - OBJECTIVE: To study the cause of myocardial rupture and its related complications
      using a computer-assisted model of left ventricular (LV) function following acute
      myocardial infarction. DESIGN: A model previously described by other authors was
      modified. The LV was portrayed as a three-layered ellipsoid at end-diastolic
      volume (135 mL). The aspect ratio of the ellipsoid's semi-minor: semi-major axis
      was 0.6. The apical middle layer was infarcted with an angle of damage of 40%,
      the infarcted layer being 81.8% of total LV wall thickness. A one-half symmetry
      condition generated an axisymmetrical, linear, elastic finite element model with
      1056 first-order elements and 1127 nodes. The endocardial surface was subjected
      to static internal pressure, modelling the instant of end-isovolumetric
      contraction. Noninfarcted myocardium was assumed to be variably stiffer than
      infarcted muscle. A simple orthotropic model was used to approximate the
      directional characteristics of muscle layers. RESULTS: Maximum von Mises stresses
      were found on the endocardial surface near the centre and edge of the angle of
      damage, the latter generally observed as the site of myocardial rupture. Static
      stress concentration factors were computed for the isotropic and orthotropic
      cases. The directional characteristics of the myocardium appeared to be
      protective. CONCLUSIONS: A more complete pathogenic model for myocardial rupture
      following acute infarction is stress concentration --> endocardial tear -->
      dissecting hemorrhage. Marked deformation is predicted in the endocardial surface
      within the angle of damage, consistent with the correlation between acute
      myocardial infarction and LV aneurysm formation.

PMID- 7585274
TI  - Morphological characteristics of the regurgitant rheumatic mitral valve.
AB  - Reparative surgery for valvular insufficiency is attempted frequently. The
      success of surgery depends partly on the underlying etiology. To establish the
      morphological characteristics of rheumatic mitral valve disease (insufficiency)
      (n = 12), mitral insufficiency due to infective endocarditis (n = 12), mitral
      insufficiency postinfarction (n = 6), rheumatic (predominant) mitral
      insufficiency postinfarction (n = 6), rheumatic (predominant) mitral stenosis (n
      = 12) and normal patients (n = 12) were examined retrospectively. In the groups
      of patients with mitral insufficiency< the mobility of the posterior leaflet tip
      (change in angle from the annular plane) was significantly less than normal 48 +/
      9 degrees only in the rheumatic group (12 +/- 7 degrees, P < 0.01). The
      posterior mitral leaflet tip had greater than normal mobility in the other mitral
      insufficiency groups: infective endocarditis 53 +/- 15 degrees (P = 0.35 versus
      normals), postinfarction 63 +/- 11 degrees (P = 0.02 versus normals), myxomatous
      63 +/- 19 degrees (P = 0.03 versus normals). The mobility of the posterior mitral
      leaflet tip was also significantly less than normal in the rheumatic mitral
      stenosis group: 16 +/- 7 degrees, P < 0.01 versus normals. In the two rheumatic
      groups, diastolic doming of the anterior mitral leaflet was seen solely in mitral
      stenosis. In the predominant regurgitant group, the tip of the anterior mitral
      leaflet was much more mobile than in the stenosis group. Doming of the anterior
      mitral leaflet was absent from the predominant regurgitant group (2.1 +/- 0.9 cm,
      P < 0.001). The stenotic mitral valves domed 0.75 +/- 0.15 cm.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7585275
TI  - Comparison of in-hospital mortality from myocardial infarction in the pre- and
      post-thrombolysis eras at the Royal University Hospital, Saskatoon, Saskatchewan.
AB  - PURPOSE: To compare in-hospital mortality of acute myocardial infarction (AMI) in
      two groups of patients in the pre- (1978-79) and post- (1990-91) thrombolysis era
      via a retrospective study. DATA SOURCE: Hospital files of patients discharged
      from the Royal University Hospital (RUH) in Saskatoon, Saskatchewan with the
      diagnosis of AMI. RESULTS: The diagnosis of AMI was established in 125 patients
      in 1978-79 and in 164 patients in 1990-91. The two groups were comparable with
      exceptions noted in the recorded family history of myocardial infarction and
      hypercholesterolemia. The overall in-hospital mortality decreased from 21.6%
      (1978-79) to 11.0% (1990-91; P = 0.05). The difference was more significant for
      patients admitted directly to the RUH, 24.0% (1978-79) versus 7.0% (1990-91; P =
      0.05), and for patients over the age of 70 years. Marked differences were
      observed in the treatments provided to patients between these two decades.
      CONCLUSIONS: The in-hospital mortality of patients with AMI has decreased
      considerably in the past two decades. The use of thrombolytic agents,
      acetylsalicylic acid, heparin and beta-blockers may have contributed to these
      changes. A worse prognosis was observed with advancing age, hypotension on
      admission and the development of congestive heart failure, malignant arrhythmias
      or shock.

PMID- 7585277
TI  - Propionibacterium acnes endocarditis.
AB  - Propionibacterium acnes endocarditis is a rare disease. A case of prosthetic
      valve endocarditis involving P acnes complicated by multiple mycotic aneurysms is
      reported. A brief review of the literature is presented.

PMID- 7585279
TI  - Ethanol- and threonine-induced hypertension in rats: a common mechanism.
AB  - OBJECTIVE: To investigate the effects of oral L-threonine and ethanol, precursor
      of endogenous acetaldehyde, on systolic blood pressure, cystolic free calcium
      ([Ca2+]i) and vascular calcium uptake in Wistar-Kyoto (WKY) rats. METHODS: Twenty
      four male WKY rats aged eight weeks were divided into four groups of six animals
      each. Animals were given either water or 5% ethanol, 8% L-threonine or 8% L
      glycine in drinking water for 15 weeks, animals were sacrificed, aortic rings
      were incubated in physiological buffer containing 45Ca2+ and uptake was measured
      after 20 mins. ([Ca2+]i in platelets was measured with a fluorescence [Ca2+]i
      indicator, FURA-2. Tissues were processed for morphological investigation.
      RESULTS: After 15 weeks, systolic blood pressure, platelet [Ca2+]i and aortic
      calcium uptake were all significantly higher (P < 0.001) in rats given either
      threonine or ethanol than in control rats given water or glycine. Animals in
      threonine or ethanol group also showed smooth muscle cell hyperplasia, with some
      thickening of the wall and narrowing of the lumen in small arteries and
      arterioles of the kidney. Glycine treatment did not cause any of these changes in
      rats. CONCLUSION: These results suggest that acetaldehyde may be a common cause
      of both ethanol- and threonine-induced hypertension.

PMID- 7585276
TI  - Quality of life, bypass surgery and the elderly.
AB  - OBJECTIVE: To examine changes in health-related quality of life (HQOL) following
      coronary artery bypass surgery (CABS) in elderly patients and to compare patient
      ratings with proxy ratings. DESIGN: Descriptive, nonrandomized, prospective
      study. SETTING: Patients from a single primary care facility in a major urban
      centre within a one-year period. PATIENTS: All eligible patients undergoing CABS
      at the site within a one-year period were approached for study participation. The
      study sample consisted of 18 patients 65 years of age or older and 18 proxies at
      baseline. Fourteen patients and 13 proxies completed follow-up assessments.
      INTERVENTIONS: All patients underwent CABS. HQOL was studied using the Sickness
      Impact Profile (SIP) and the Psychological Well-Being Schedule (PGWB). MAIN
      RESULTS: Significant improvements were noted in physical, social and
      psychological functioning (P < 0.05). Proxies' reports provided good indications
      of patient functioning for these dimensions with significant differences found
      only for certain preoperative measures including the total SIP score and the
      Anxiety and Depression subscales of the PGWB (P < 0.05). CONCLUSIONS: Patients 65
      years of age and older accrue improvements in HQOL following CABS. Such findings
      may influence the allocation and justification of various medical procedures.
      Proxy ratings closely reflected the patients' own ratings and may therefore be
      considered a reliable, alternate source of information.

PMID- 7585280
TI  - Clentiazem and diltiazem preserve endothelium-dependent relaxation following
      global rat heart ischemia.
AB  - OBJECTIVE: To evaluate the effects of the calcium channel blocker diltiazem and
      its chloride derivative clentiazem on coronary vasoregulation of isolated rat
      hearts exposed to ischemia-reperfusion. Diltiazem has been reported to prevent
      postreperfusion myocardial damage but its beneficial effects on coronary blood
      flow regulation remain uncertain. METHODS: Two groups of hearts were pretreated
      with a 10 min infusion of either diltiazem (10(-9) to 10(-6) mol/L) or clentiazem
      (10(-9) to 10(-7) mol/L) (n = 6 for each concentration) and exposed to 30 mins of
      no-flow ischemia. Another group (n = 6) received no pretreatment and was used as
      control. Endothelium-dependent and -independent relaxation were tested by
      assessing coronary flow increase to 5-hydroxytriptamine (10(-6) mol/L) and sodium
      nitroprusside (10(-5) mol/L) infusions, respectively, and were assessed before
      and after ischemia-reperfusion. Left ventricular pressure, dP/dt and coronary
      basal flow were also recorded. Postreperfusion results are expressed as a
      percentage of pre-ischemic value. Dunnet variance analysis was used to compare
      means of pretreated groups with the control group. RESULTS: Endothelium-dependent
      relaxation was significantly improved with both drugs. Optimal preservation was
      obtained with diltiazem 10(-6) mol/L (66 +/- 4%) and clentiazem 10(-7) mol/L (83
      +/- 4%), whereas endothelial response was almost abolished in control hearts (6
      +/- 11%, P < 0.01). Clentiazem was found to be more potent than diltiazem at low
      concentration (10(-9) mol/L, clentiazem 89 +/- 13% versus diltiazem 3 +/- 16%, P
      < 0.05). Optimal endothelium-independent relaxation preservation was achieved at
      10(-8) mol/L in both groups (diltiazem 86 +/- 4%, clentiazem 82 +/- 8%, control
      47 +/- 10%, P < 0.05). Left ventricular pressure and dP/dt were not affected by
      any pretreatment. However, postreperfusion coronary basal flow was significantly
      increased in control hearts. CONCLUSION: This study indicated that pre-ischemic
      infusion of diltiazem and clentiazem enhances endothelium-dependent and 
      independent coronary artery relaxation following reperfusion in the isolated rat
      heart model, without affective ventricular hemodynamics, and contributes to
      preservation of coronary artery autoregulation.

PMID- 7585281
TI  - Calcium channel blockers for heart rate control in atrial fibrillation
      complicated by congestive heart failure.
AB  - OBJECTIVES: To review the safety and efficacy of verapamil and diltiazem with
      respect to ventricular response in atrial fibrillation (AF) in the setting of
      left ventricular (LV) systolic dysfunction. DATA SOURCES: Pertinent articles were
      identified through a MEDLINE search of the English language literature from 1984
      to 1993, followed by a manual search of the bibliographies of pertinent articles.
      STUDY SELECTION: Studies selected were case reports, controlled trials, review
      articles and editorials. DATA EXTRACTION: Effects of verapamil and diltiazem on
      hemodynamics, ventricular response in AF, clinical parameters and mortality were
      reviewed. DATA SYNTHESIS: There are limited data about the effects of verapamil
      and diltiazem on ventricular function in patients with congestive heart failure.
      In vitro diltiazem has fewer negative inotropic effects than verapamil.
      Clinically there are some reports of hemodynamic and clinical deterioration in
      patients with significant LV dysfunction given verapamil although most patients
      improve with verapamil. There are more data concerning diltiazem in the setting
      of AF complicated by congestive heart failure. The drug does not appear to
      exacerbate heart failure, although hypotension can result. In chronic AF
      complicated by heart failure, there is concern that diltiazem may increase
      mortality. Options for therapy are digoxin, beta-blockers and atrioventricular
      node ablation. CONCLUSIONS: Calcium channel blockers may have a role in the acute
      reduction of ventricular response in patients with AF complicated by congestive
      heart failure; however, their safety in chronic heart rate control remains to be
      proven.

PMID- 7585278
TI  - Disorders of body fluid balance: a new look into the mechanisms of disease.
AB  - OBJECTIVE: To review the mechanisms of disease on the basis of dysfunction in
      body fluid distribution secondary to abnormalities in capillary permeability and
      plasma membrane transport disorders, leading to quantitative and qualitative
      alterations of the interstitial space, a mainly strategic compartment positioned
      between the microcirculation and cell mass. DATA SOURCES: The recent literature
      on the mechanisms involved in the control of body fluid balance, with special
      reference to microcirculation and interstitial compartment physiology, as well as
      published and unpublished original data from the authors laboratory. DATA
      EXTRACTION AND SYNTHESIS: To illustrate the importance of capillary permeability
      dysfunction in the development of disease, animal (rat and dog) models of chronic
      renal failure, acute diuretic-induced fluid depletion, diabetes mellitus,
      arterial hypertension and ischemia-reperfusion of the kidney were used in an
      attempt to show that in all these experimental models, basic capillary
      permeability dysfunction (measured by the extravasation of Evans blue, a marker
      of albumin leakage) develops in specific microcirculation beds. As a consequence,
      tissue edema (interstitial and/or cellular) develops and likely impairs the
      traffic of nutrients and waste products to and from the cellular mass, and/or
      challenges the microcirculation, leading to organ damage. Kidney dysfunction is
      measured by conventional clearance methods (renal hemodynamics and tubular
      function). In some models, the eventual mediators of vascular abnormality are
      examined by use of pharmacological tools. CONCLUSIONS: The critical role of
      microcirculation dysfunctions, in particular capillary permeability, resulting in
      interstitial compositional changes is presented as the basis of disease. The
      apparent specificity of target organ damage may represent the nonspecific result
      of physicochemical alteration in the strategic interstitial fluid compartment.

PMID- 7585282
TI  - Antioxidants in the Mediterranean diet.
AB  - It has been suggested that antioxidant vitamins or other antioxidants might
      inhibit the oxidation of low density lipoproteins into a particularly atherogenic
      form and preserve endothelial function. Antioxidants in the Mediterranean diet
      have been evaluated in relation to cardiovascular disease protection in this
      area. Observational epidemiologic data obtained from case-control, cohort or
      cross-cultural studies have consistently suggested that persons, such as those
      living in the Mediterranean area, who consume large amounts of antioxidant
      vitamins have a lower than average risk of cardiovascular disease. In another
      cross-cultural comparison, dietary intake, antioxidant status and plasma lipid
      peroxidation were compared in healthy young persons in Naples (Southern Italy)
      who consumed typical regional foods, and in Bristol (UK). The Naples group
      consumed more tomatoes and tomato juice, a higher proportion of monounsaturated
      fatty acids (from olive oil) and had a higher level of lipid antioxidant vitamin
      E (P = 0.005) and of beta carotene (P < 0.001) than the Bristol group. The intake
      of vitamin C, fresh fruit and vegetables, plasma vitamin A, serum selenium and
      copper levels did not differ. Several indices of plasma lipid peroxidation were
      significantly lower in the Naples group: conjugated dienes (P < 0.001), diene
      conjugation index (P = 0.019), lipid peroxides (P < 0.001). Dietary habits
      leading to relatively low levels of oxidized lipoproteins might contribute to the
      lower risk of coronary artery disease in Southern Italy.

PMID- 7585283
TI  - Relationships between nutrient intake and progression/regression of coronary
      atherosclerosis as assessed by serial quantitative angiography.
AB  - To elucidate the direction and magnitude of effects of nutrition on coronary
      artery disease (CAD), the relation between nutrient intake and angiographic
      changes were examined in the course of a controlled dietary trial. Ninety men
      with symptomatic CAD and serum cholesterol greater than 232 mg/dL were entered
      into a randomized controlled trial of a lipid-lowering diet, or of diet plus
      cholestyramine, compared with usual cardiac care. Of those in the first and
      second groups, 50 patients completed the trial and are the subject of this
      report. Quantitative coronary angiography was performed at baseline and at 39
      months. From repeated dietary assessment during the trial, mean nutrient intakes
      were computed, and their relationships with change of coronary artery narrowing
      were analyzed. Progression of coronary disease was directly, strongly and
      independently associated with intake of saturated fatty acids of chain length 14
      18. This was not fully explained by the effects of saturated fat in raising serum
      cholesterol; after adjustment for low density lipoprotein cholesterol level,
      stearic acid (C18:0) intake remained independently predictive of progression. No
      'protective' effect of linoleic, linolenic or eicosapentaenoic acid was
      demonstrable. Intake of trans fatty acids was directly related to progression.
      Together with the favourable treatment effects on angiographic appearance and
      clinical end-points, these findings provide further support for a causal role of
      saturated fats in CAD; restriction of foods containing such fats should be
      emphasized as part of regimens aimed to reduce progression of coronary
      atherosclerosis.

PMID- 7585284
TI  - Role of dietary cholesterol in the optimal diet for the treatment of
      hypercholesterolemia.
AB  - OBJECTIVE: This paper discusses studies in which the effects of dietary
      cholesterol on the plasma concentrations of lipids and lipoproteins have been
      evaluated in adult human subjects including patients with hypo- and
      hypercholesterolemia. DESIGN: The dietary studies were conducted on an outpatient
      basis in the Clinical Research Center. Each dietary period was four weeks in
      duration and an adequate washout period was interposed between each dietary
      phase. SETTING: A university medical centre. PATIENTS: The participants in these
      studies were adult men or women with hypocholesterolemia, normal volunteers or
      patients with primary hypercholesterolemia. INTERVENTIONS: The dietary periods
      consisted of three separate dietary phases in which dietary cholesterol was a
      single variable. The diets contained 50 mg/day of cholesterol for the low
      cholesterol diet, 350 mg/day for the moderate cholesterol diet and 650 mg/day for
      the high cholesterol diet. RESULTS: Concentrations of total and low density
      lipoprotein (LDL) cholesterol increased in all three patient groups from the low
      cholesterol to the moderate cholesterol to the high cholesterol diet but the
      magnitude of increase in LDL cholesterol concentrations was greater in the
      patients with pre-existent hypercholesterolemia and least in the patients with
      hypocholesterolemia. In all three patients groups an increased intake of dietary
      cholesterol was associated with suppression of endogenous cholesterol
      biosynthesis as assessed by the urinary excretion of mevalonic acid. CONCLUSIONS:
      An increased intake of dietary cholesterol results in increases in the plasma
      concentrations of total and LDL cholesterol in patients with inherently low,
      normal or high concentrations of LDL cholesterol but the magnitude of increase is
      greatest in those patients with pre-existent hypercholesterolemia. These results
      support the view that restriction of dietary cholesterol leads to a reduction in
      the plasma concentrations of total and LDL cholesterol and is an appropriate
      recommendation for patients with known hypercholesterolemia or patients in whom
      medical recommendations call for a reduction in the plasma concentrations of
      total and LDL cholesterol.

PMID- 7585285
TI  - Optimal diet for reducing the risk of arteriosclerosis.
AB  - The primary objectives of current dietary advice for those at risk from coronary
      artery disease (CAD) focus on progressive restriction of dietary saturated (and
      trans) fatty acids and cholesterol intake, combined with exercise and achievement
      of ideal body weight. These principles are endorsed by the official bodies of
      most western nations concerned with reducing CAD mortality and have recently been
      reaffirmed by the Adult Treatment Panel of the National Cholesterol Education
      Program. There has been concern, however, in view of the increasing use of drug
      therapy, that additional strategies should supplement the primary goals to
      increase the palatability and effectiveness of the diet. These additional
      strategies include increased intake of foods high in soluble viscous fibres,
      vegetable proteins, possibly antioxidants such as vitamin E and the
      isoflavonoids, increased intake of alpha-linolenic acid and, for those with low
      high density lipoprotein cholesterol levels, increased monounsaturated fat
      intake. These strategies translate into advice to significantly increase
      consumption of specific plant foods such as green leafy vegetables, nuts and
      seeds, and dried legumes, all of which improve the overall nutritional quality of
      the diet and contain specific active ingredients. These changes represent a
      regression to a more primitive diet on the evolutionary scale.

PMID- 7585286
TI  - Dietary cholesterol and the optimal diet for reducing risk of atherosclerosis.
AB  - The importance of dietary cholesterol in the incidence of hypercholesterolemia in
      the population remains a topic of scientific debate. Analysis of the results from
      over 30 years of cholesterol feeding studies (n = 128) in more than 2750 patients
      indicate that for the majority of individuals modest changes in dietary
      cholesterol have little if any effect on plasma lipoprotein cholesterol levels.
      Data demonstrate that on average a change in cholesterol intake of 100 mg/day
      results in a change in plasma total cholesterol of 0.07 mmol/L (2.5 mg/dL). The
      studies also show that the extent of response to dietary cholesterol is
      independent of the amount of dietary fat and of the baseline plasma cholesterol
      level. In contrast, the dose adjusted plasma cholesterol response to a dietary
      cholesterol challenge is affected by the type of dietary fat and the baseline
      dietary cholesterol intake. Based on these data a reduction in dietary
      cholesterol intake from 450 to 300 mg/day will, on average, lower plasma
      cholesterol levels by 0.10 mmol/L (3.7 mg/dL). This decrease is modest and highly
      variable due to significant interindividual heterogeneity of responses. It is
      estimated that one-third of the population is sensitive to dietary cholesterol
      whereas two-thirds are resistant to plasma cholesterol changes. In comparison, a
      1% decrease in energy intake from saturated fat decreases plasma cholesterol 0.08
      mmol/L (3 mg/dL). Consumption of products marketed as 'No cholesterol' with high
      total and saturated fat clearly does not contribute to the optimal diet for
      reducing plasma cholesterol levels of risk of atherosclerosis.

PMID- 7585288
TI  - The concept and history of satellite symposia associated with international
      symposia on atherosclerosis.

PMID- 7585291
TI  - Dietary trans fatty acids and their impact on plasma lipoproteins.
AB  - Foods contain isomers of unsaturated fatty acids that have double bonds in
      unusual configurations (trans instead of cis) or unusual positions, or both. Such
      fatty acids arise through biohydrogenation in the rumen of cows and sheep or
      catalytic hydrogenation in industrial hardening of oils. The effects of
      transmonounsaturates on lipoproteins in man are opposite to those of their cis
      isomer, oleic acid: trans fatty acids raise low density lipoprotein (LDL)
      cholesterol and lipoprotein Lp(a) and lower high density lipoprotein (HDL)
      cholesterol, all in a dose-dependent fashion. Trans fatty acids raised serum
      cholesteryl ester transfer activity in 52 of 55 volunteers (mean change 18%, P <
      0.02), and lowered the ratio of cholesteryl esters to triglycerides in HDL.
      Lecithin cholesterol acyl transferase was unchanged. The effects of trans fatty
      acids on HDL and LDL may thus be mediated through cholesterol ester transfer
      protein.

PMID- 7585289
TI  - Individuality of lipemic responses to diet.
AB  - The objective of this review is to assemble reports dealing with variability in
      the lipemic responses of both humans and experimental animal models to dietary
      fat and cholesterol; to extract indications of the metabolic processes
      controlling responsiveness; and, if possible, identify allelic variations in
      genes that are responsible for these difference in responses to diet. There is
      strong evidence of genetic control of lipemic responsiveness to dietary fat and
      cholesterol in several animal species (rabbit, swine, mouse, marsupial, squirrel
      monkey, rhesus monkey, cynomolgus monkey and baboon). Variations in bile acid
      secretion and cholesterol absorption are the metabolic variables most commonly
      associated with responsiveness. The metabolic process most frequently associated
      with human responsiveness is low density lipoprotein apoB production rate. The
      mechanism controlling dietary responsiveness varies among species and, in humans,
      probably among individuals. No genetic polymorphism is unequivocally identified
      as responsible for individual variability.

PMID- 7585287
TI  - Potential role of raising dietary protein intake for reducing risk of
      atherosclerosis.
AB  - OBJECTIVE: To ascertain the effect on plasma lipoprotein lipids of substituting
      moderate amounts of protein for carbohydrate in human diets. DESIGN: Subjects
      were first stabilized on the desired fat intake for one to two weeks. Using a
      cross-over design, subjects were randomly allocated to either the high or low
      protein diet for four to five weeks and then switched to the alternative diet for
      four to five more weeks. Fasting venous blood was obtained weekly. SETTING:
      Subjects were studied in tertiary care lipid clinic setting. PATIENTS: Studies in
      two groups of hypercholesterolemic subjects have been completed: group MH - 10
      subjects with moderate hypercholesterolemia (5.8 to 8.0 mmol/L) and group FH -
      five subjects with familial hypercholesterolemia (more than 8.2 mmol/L prior to
      treatment with cholestyramine). Preliminary findings in Group NL - six
      normolipidemic subjects (3.5 to 4.9 mmol/L) are also discussed briefly.
      INTERVENTIONS: Body weight, intakes of fat, fibre and cholesterol and fat
      composition were constant. Either 11, 17 or 10% of total energy from protein was
      exchanged for carbohydrate in groups MH, FH and NL, respectively. MAIN RESULTS:
      Exchange of dietary protein for carbohydrate: significantly reduced mean plasma
      low density lipoprotein (LDL) cholesterol 6% in group MH and 9% in group NL (P <
      0.02); significantly increased mean fasting plasma high density lipoprotein (HDL)
      cholesterol by 12% in group MH and by 17% in group FH (P < 0.01); significantly
      reduced the mean value for the ratio of plasma total cholesterol to HDL
      cholesterol by 15% in group MH and by 16% in group FH (P < 0.05); and
      significantly reduced fasting total triglycerides by 23% in groups MH and FH and
      by 18% in NL (P < 0.05). CONCLUSION: Substitution of dietary protein for
      carbohydrate favourable alters human blood cholesterol cardiovascular risk
      profiles.

PMID- 7585292
TI  - Saturated fats and blood lipids: new slant on an old story.
AB  - In recent years the association between dietary saturated fat,
      hypercholesterolemia, and coronary artery disease has been re-explored. Prompted
      largely by the notion that dietary fats, and their attendant fatty acids, can
      specifically influence the distribution of the plasma cholesterol between low
      density (LDL) and high density (HDL) lipoprotein cholesterol, the focus of the
      original research has shifted from total cholesterol to lipoproteins. Several
      new, sometimes controversial, concepts have arisen that challenge underlying
      assumptions of the Keys-Hegsted regression equations. First, although saturated
      fats as a class raise LDL, they also appear to have primary responsibility among
      dietary fatty acids for raising HDL, possibly depending on a balanced intake of
      polyunsaturated fats. Second, not all saturated fatty acids are equally
      responsible for changes in LDL or HDL. Only natural triglycerides (TG) rich in
      lauric (12:0) and myristic (14:0) acids are especially cholesterolemic, whereas
      16:0-rich fats can be neutral or cholesterol-raising depending on the metabolic
      circumstances (lipoprotein setpoint) of the host. In normolipemic individuals
      with normal lipoprotein metabolism, dietary palmitic acid (16:0) typically
      appears neutral. When lipoprotein metabolism is impaired, eg, if LDL receptor
      activity is depressed by the presence of dietary cholesterol, consumption of 16:0
      rich TGs can contribute to hypercholesterolemia. Although stearic acid (18:0) is
      typically considered neutral, exaggerated consumption of 18:0-rich fat (cocoa
      butter) lowers both LDL and HDL. Third, the saturated fat effect is related both
      to the dietary cholesterol load and the lipoprotein setpoint of the host, eg,
      16:0 becomes progressively cholesterolemic as dietary cholesterol raises the
      setpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585293
TI  - Omega-3 fatty acids--nutritional aspects.
AB  - Omega-3 fatty acids contain a double bond in the third position from the methyl
      group. The very long-chain (20 or 22 carbon atoms) omega-3 fatty acids are mostly
      found in fatty fish and fish oils. The omega-3 fatty acids are essential and may
      act as precursors for eicosanoids, altering membrane fluidity or binding to
      transcription factors. Dietary intake of omega-3 fatty acids reduces plasma
      concentration of triglycerides, probably by decreasing hepatic secretion of very
      low density lipoprotein (VLDL) and by increasing catabolism of chylomicrons. In
      addition, lipid peroxidation of omega-3 fatty acids may take place, with good and
      bad consequences. As the number of double bonds is high, the omega-3 fatty acids
      may easily react with oxygen radicals. We performed studies where 5 g/day of very
      long-chain omega-3 fatty acids was given as a supplement for four months along
      with vitamin E, whereas control groups received similar amounts of other oils.
      The unsaturation index was higher in fatty acids of LDL from individuals exposed
      to omega-3 fatty acids, and the amounts of cholesteryl esters and total lipids
      were lower compared with control LDL, whereas similar electrophoretic mobility
      and apolipoprotein B structure were observed. There was a decrease in the melting
      temperature of cholesteryl esters in omega-3 fatty acid-enriched LDL, but no
      change in the susceptibility of LDL to Cu2+ catalyzed lipid peroxidation, as
      measured by changes in amounts of lipid peroxides or in the uptake of LDL in
      macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585294
TI  - Dietary fibre, complex carbohydrate and coronary artery disease.
AB  - Animal studies indicate that viscous, soluble fibres such as psyllium, oat gum,
      guar gum and pectin have substantial hypocholesterolemic effects. Epidemiologic
      data suggest that the intake of complex carbohydrate and dietary fibre is
      associated in an inverse manner to risk for coronary artery disease (CAD). Two
      long term clinical trials indicate that increasing soluble fibre intake as part
      of a low fat, low cholesterol diet reduces serum cholesterol concentration from 3
      to 5% below that for the low fat, low cholesterol diet. Short term, controlled
      clinical trials indicate that oat bran or beans, in a metabolic ward setting,
      decrease serum cholesterol concentrations of hypercholesterolemic individuals by
      10 to 12%. Studies of free-living hypercholesterolemic individuals document that
      incorporation of oat products, psyllium or guar gum into the diet decreases serum
      cholesterol by 6 to 8%. Other studies suggest that increased fibre intake may
      decrease blood pressure slightly, assist in weight management, alter blood
      clotting factors, and increase insulin sensitivity. Intake of dietary fibre and
      complex carbohydrate appear to have a protective role for CAD. Further controlled
      clinical trials are required to examine the role of fibre and complex
      carbohydrate in prevention or regression of CAD.

PMID- 7585290
TI  - Essentiality of omega-3 and omega-6 fatty acids for efficient liver sterol
      metabolism.
AB  - Abundant data from both experimental animals and humans now support the
      conclusion that the incidence of atherosclerosis is related to the concentration
      of plasma cholesterol. Cholesterol homeostasis in the body is maintained by
      regulatory mechanisms, which control the input and output processes. The liver
      plays a key role in cholesterol balance. In this organ, the major part of the
      cholesterol synthesis, cholesterol conversion to bile acids and the delivery of
      cholesterol to the plasma in the form of lipoprotein remnants, low and high
      density lipoproteins. While many studies have related dietary intake of fatty
      acids to concentrations of cholesterol in the circulation, their potential
      effects on liver sterol metabolism have received relatively less attention.
      However, the liver represents the target of many stimuli capable of affecting
      cholesterol homeostasis. This review will focus on the regulation of liver sterol
      metabolism by omega-3 versus omega-6 fatty acids.

PMID- 7585296
TI  - Nutrition and Atherosclerosis. Proceedings of a satellite symposium of the Xth
      International Symposium on Atherosclerosis. Quebec City, Quebec, October 6-8,
      1994.

PMID- 7585295
TI  - Role of dietary fish protein in the regulation of plasma lipids.
AB  - The following studies have been carried out to compare the effects of fish
      protein with other dietary proteins on plasma cholesterol and lipoproteins in
      animal models and in humans. In rabbits, fish protein has been shown to induce
      relatively variable effects compared to casein and soy protein on serum
      cholesterol depending in part on the origin of dietary lipids with which it is
      combined. In a protein-lipid interaction study, casein, soy or cod protein were
      combined with corn or coconut oil. Casein and soy protein in the presence of corn
      oil induced lower serum cholesterol levels despite its combination with either
      corn or coconut oil. This is in part due to serum high density lipoprotein (HDL)
      cholesterol concentrations, which were consistently higher with cod protein than
      with either casein or soy protein, regardless of the dietary lipid source. In
      rabbits, this rise in HDL cholesterol was associated with a decrease in very low
      density lipoprotein (VLDL) triglycerides and an increase in postheparin plasma
      lipoprotein lipase activity. The effects of lean white fish on plasma
      lipoproteins also have been investigated in post and premenopausal women fed a
      low-fat, high P/S (polyunsaturated/saturated fat) ratio diet. In postmenopausal
      women, lean white fish compared with other animal protein products induced higher
      concentrations of plasma cholesterol, LDL-apolipoprotein (apo) B and HDL
      cholesterol, mainly in the HDL3 fraction. In premenopausal women, lean white fish
      induced lower concentrations of VLDL triglycerides and higher concentrations of
      LDL-apoB in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585297
TI  - Nutritional regulation of lipoprotein lipase.
AB  - Lipoprotein lipase (LPL) is needed for normal catabolism of triglyceride-rich
      lipoproteins. In some tissues, notably the adipose tissue, the local LPL activity
      is an important determinant for how much lipid is taken up. There is regulation
      of gene expression, but the rapid changes that occur in response to the
      nutritional state are mediated mainly by post-transcriptional mechanisms. In the
      fed state, the adipose tissue expresses its full potential for LPL production, as
      set by the mRNA levels and the rate of protein synthesis. During fasting, LPL
      activity is suppressed by an unknown post-translational mechanism. In heart,
      regulation is primarily exerted on the equilibrium between LPL at endothelial
      sites and LPL in blood, with more endothelial LPL in the fasted state. LPL forms
      complexes with fatty acids which results in shut-down of lipolysis and detachment
      of both lipase and lipoproteins from the endothelial site. This provides a
      molecular coupling device between the cellular metabolic state and the rate of
      lipoprotein catabolism. There is growing evidence that LPL is a ligand for
      binding of lipoprotein particles such as chylomicron remnants to cell surfaces
      and receptors.

PMID- 7585299
TI  - Genetic variation of apolipoprotein B can produce both low and high levels of
      apoB-containing lipoproteins in plasma.
AB  - The polymorphic markers of the apolipoprotein B (apoB) gene include restriction
      fragment length polymorphisms (RFLPs) scattered along the length of the gene, an
      insertion/deletion (I/D) polymorphism at the 5' and variable numbers of tandem
      repeats (VNTRs) at the 3' untranslated ends. The Xbal and I/D polymorphisms which
      do not affect apoB structure, produce modest effects on fasting and postprandial
      lipids and on responsiveness to dietary lipids, but the effects are population,
      age and gender-dependent. Much larger effects on fasting lipid levels are
      produced by structural mutations of the apoB gene. The apoB 3500 mutation
      affecting the low density lipoprotein (LDL) receptor recognition region of apoB
      100, is one of the causes of the autosomal codominant familial
      hypercholesterolemia phenotype, characterized by fasting LDL elevations and
      atherosclerosis. Neither fasting nor postprandial hypertriglyceridemia are
      consistently present. Some forms of familial hypobetalipoproteinemia (FHBL) are
      genetically linked to various truncation-producing mutations of the gene. To date
      approximately 30 deletion, insertion or non-sense mutations have been identified
      resulting in apoB truncations ranging in size from apoB-9 to apoB-89. FHBL
      segregates as an autosomal dominant trait. Heterozygotes have less than a 5th to
      10th percentile levels while compound heterozygotes and true homozygotes have
      much less than 5th percentile levels of total and LDL cholesterol. Heterozygotes
      have no symptoms traceable to the gene defect. Alterations in the distributions
      of apoB truncations among the lipoproteins in plasma and in the metabolism of the
      lipoproteins containing apoB-truncations depend on the lengths of the
      truncations.

PMID- 7585298
TI  - Restriction fragment length polymorphism of the apolipoprotein B gene and
      response to dietary fat and cholesterol.
AB  - OBJECTIVE: The relationship between response to dietary fat and cholesterol, and
      the EcoRI restriction fragment length polymorphism (RFLP) of the apolipoprotein
      B(apoB) gene was examined. DESIGN: Forty-nine free-living subjects took part in a
      prospective double-blind crossover dietary intervention study. The apoB EcoRI
      cutting site was present in five women and 18 men (E+) and absent in 15 women and
      11 men (E-). INTERVENTION: Subjects consumed a low fat (25% energy), low
      cholesterol (less than 200 mg/day) diet. After two weeks on this background diet
      (baseline) subjects were randomly assigned to consume a liquid supplement for
      three weeks which was either fat and cholesterol free or which contained fat (30
      to 36 g) and cholesterol (650 to 780 mg). After the first three-week period
      subjects switched to the other supplement. Blood samples were collected for
      plasma lipid analysis after an overnight fast on two consecutive days at the end
      of baseline and on three consecutive days after each three-week supplement
      period. RESULTS: There was no significant difference in response to diet between
      the RFLP groups. Changes in plasma total, low density lipoprotein (LDL), high
      density lipoprotein(HDL), HDL2 and HDL3 cholesterol or plasma triglyceride were
      not different between the two RFLP groups. There was a significant difference
      between RFLP groups for baseline HDL2-cholesterol (0.31 +/- 0.04 and 0.16 +/-
      0.02 mmol/L for E- and E+ subjects, respectively) which was independent of sex
      and apoE genotype (P = 0.032). CONCLUSIONS: These results indicate that the EcoRI
      RFLP of the apoB gene is not associated with response to dietary fat and
      cholesterol.

PMID- 7585300
TI  - Controlling coronary risk through nutrition.
AB  - The epidemic of coronary artery disease (CAD), the main cause of deaths in
      'western' countries, could have been avoided through appropriate lifestyles of
      eating and activities. The dramatic decline in CAD in some countries is more
      difficult to attribute to changes that is the rapid rise in eastern European
      countries (high dietary saturated fat plus smoking). While CAD rates in
      Asian/Pacific countries are relatively low, subgroups, mainly through affluence,
      show high rates. Inappropriate eating patterns are superimposed on genetic
      factors (commonly diabetes in Asia) and on other lifestyle factors (smoking).
      Eventually the combination of dyslipidemia ('high triglyceride-low high density
      lipoprotein' in Asia Pacific rim), plus smoking plus hypertension (part salt
      related) may trigger a CAD epidemic. The challenge is better public health
      management including balancing the nature of the food supply with the nutritional
      needs for preventing CAD through national food and nutrition policies. Critical
      are the sources of fats (often key economic commodities), the amount of salt,
      preventing obesity especially of the central type, and provision of plant foods
      with a better understood mix of fatty acids, antioxidants and specific starches
      and nonstarch polysaccharides. The anti-atherogenic effects of specific
      antioxidants and of n-3 fatty acids in fish probably explain the lower than
      expected CAD rates in several countries. Although many of the risk factors are
      common, important regional differences demand national strategies, while
      providing wider perspectives on the multifactorial nature of the disease and the
      value of certain traditional diets.

PMID- 7585303
TI  - Nursing informatics. Making financial management come alive.
AB  - The authors describe integration of nursing informatics concepts and computer
      based instructional strategies in a financial management course for graduate
      level nursing administration students. Major components include: 1) computer
      based instruction for financial management theory; 2) spreadsheet used for
      decision support; 3) utilization of forecasting software; and 4) evaluation of
      learning involving computer use.

PMID- 7585302
TI  - Effect of vitamin E, vitamin C and beta-carotene on LDL oxidation and
      atherosclerosis.
AB  - OBJECTIVE: The oxidative modification of low density lipoprotein (LDL) may be an
      early step in atherogenesis. Furthermore, evidence of oxidized LDL has been found
      in vivo. The most persuasive evidence shows that supplementation of some animal
      models with antioxidants slows atherosclerosis. The purpose of this review is to
      examine the roles that vitamin E, vitamin C and beta-carotene may play in
      reducing LDL oxidation. DATA SOURCES: English language articles published since
      1980, particularly from groups active in this field of research. STUDY SELECTION:
      In vitro, animal, and human studies on antioxidants, LDL oxidation, and
      atherosclerosis were selected. DATA SYNTHESIS: Vitamin E has shown the most
      consistent effects with regard to LDL oxidation. Beta-carotene appears to have
      only a mild or no effect on oxidizability. Ascorbate, although it is not
      lipophilic, can also reduce LDL oxidative susceptibility. CONCLUSIONS: LDL
      oxidizability can be reduced by antioxidant nutrients. However, more research is
      needed to establish their utility in the prevention of coronary artery disease.

PMID- 7585301
TI  - Apolipoprotein E polymorphism and dietary plasma cholesterol response.
AB  - All studies have demonstrated a strong association between plasma cholesterol and
      apoE phenotypes in the following order: E4/E4 > E4/E3 > E3/E3 > E3/E2. It has
      been thought possible that the apoE gene might be involved in the modulation of
      dietary plasma cholesterol responses, perhaps explaining the differences in
      cholesterol concentrations. Some dietary intervention studies have suggested that
      apoE4 individuals react to dietary change with exaggerated cholesterol responses.
      In one study, apoE4/E4 individuals responded by increased cholesterol reductions
      during low fat intake, and by increased cholesterol elevations during switchback
      to high fat diet. Plausible mechanisms have been postulated which could explain
      such differences. However, other studies have reported no differences in plasma
      lipid responses among apoE phenotypes. The studies cannot be directly compared
      because of different designs and study populations with differing apoE allele
      frequencies. Thus the possible role of genetic variation in the apoE gene in the
      modulation of dietary plasma lipid responses remains to be confirmed in
      prospective dietary studies, involving diets both rich and poor in fat and
      cholesterol.

PMID- 7585304
TI  - How reliable is computerized assessment of readability?
AB  - To assess the consistency and comparability of readability software programs,
      four software programs (Corporate Voice, Grammatix IV, Microsoft Word for
      Windows, and RightWriter) were compared. Standard materials included 28 pieces of
      printed educational materials on human immunodeficiency virus/acquired
      immunodeficiency syndrome distributed nationally and the Gettysburg Address.
      Statistical analyses for the educational materials revealed that each of the
      three formulas assessed (Flesch-Kincaid, Flesch Reading Ease, and Gunning Fog
      Index) provided significantly different grade equivalent scores and that the
      Microsoft Word program provided significantly lower grade levels and was more
      inconsistent in the scores provided. For the Gettysburg Address, considerable
      variation was revealed among formulas, with the discrepancy being up to two grade
      levels. When averaging across formulas, there was a variation of 1.3 grade levels
      between the four software programs. Given the variation between formulas and
      programs, implications for decisions based on results of these software programs
      are provided.

PMID- 7585307
TI  - Building a nursing activity database for processing free-text entry during
      computerized clinical simulation testing.
AB  - Computerized Clinical Simulation Testing is under research and development by the
      National Council of State Boards of Nursing for potential use as a component of
      the National Council Licensure Examination for Registered Nurses. This
      interactive software permits the realistic assessment and management of client
      needs through free-text entry of requests for nursing activities, each of which
      elicit a response from the client. The efficiency and accuracy of system
      recognition of the free-text requests depends on the careful structuring of a
      comprehensive nursing activity database. This article describes and illustrates
      the processes and challenges encountered in building a system-compatible nursing
      activity database from a very unstructured, unstandardized nursing language.

PMID- 7585306
TI  - Using interactive video to add physical assessment data to computer-based patient
      simulations in nursing.
AB  - The use of computer-based simulations can enhance problem-based learning in
      nursing education. Adding interactive video allows students to "see" the patient
      they are interviewing and to "examine" the patient rather than having the
      examination findings described by the software developer. These features both
      increase the realism of the simulations and challenge the learner to interpret
      the physical examination findings. The use of interactive videotape has proved to
      be a medium that lends itself to in-house production of interactive video.

PMID- 7585308
TI  - Air gun injuries to the eye in children: Canadian ophthalmologists have to stop
      the onslaught.

PMID- 7585305
TI  - An inductive algorithm approach to knowledge acquisition for expert system
      development. A pilot study.
AB  - Knowledge acquisition, which consists of knowledge elicitation and knowledge
      representation, often is considered the weakest link in the design of expert
      systems. Systems frequently are built on the knowledge of one expert and require
      extensive use of knowledge engineering techniques to elicit this knowledge from
      the expert. Inductive algorithms are a potential alternative method of knowledge
      acquisition for expert system development. The aim of this pilot study was to
      examine the feasibility of applying machine learning techniques, specifically,
      inductive algorithms, to an existing research database as a method for knowledge
      elicitation and knowledge representation for expert system development. Two
      inductive algorithms (C4 and Classification and Regression Trees [CART]) that
      generate decision trees were selected for the analysis using a data set of 201
      patients hospitalized for Pneumocystis carinii pneumonia. Neither C4 nor CART
      produced trees with an accuracy that was significantly better than the baseline
      accuracy (71.3%) for prediction of outcome in the data set. The mean accuracy of
      the C4 decision trees was below baseline and the mean accuracy of CART decision
      trees was 74.6%. The experts found both algorithms comprehensible, but not
      adequate, and identified important missing predictor variables. The study
      findings suggest that additional research is needed to examine the appropriate
      use of inductive algorithms in the transformation of nursing data and information
      into nursing knowledge.

PMID- 7585309
TI  - Unilateral vs. simultaneous bilateral photorefractive keratectomy.

PMID- 7585310
TI  - Air guns: the main cause of enucleation secondary to trauma in children and young
      adults in the greater Ottawa area in 1974-93.
AB  - OBJECTIVES: To determine the proportion of enucleation procedures attributable to
      injuries from air guns in people aged 18 years or less and to identify the
      associated pathological findings. DESIGN: Case series. SETTING: Ophthalmic
      Pathology Registry, University of Ottawa, and affiliated Children's Hospital of
      Eastern Ontario (Ottawa), Ottawa General Hospital and Ottawa Civic Hospital. In
      addition, information on air gun injuries from April 1990 to December 1993 was
      obtained from the Canadian Hospitals Injury Reporting and Prevention Program
      (CHIRPP) database, with data from 10 pediatric and 5 general hospitals across
      Canada. PATIENTS: All patients aged 18 years or less who underwent enucleation
      between Jan. 1, 1974, and Dec. 31, 1993. RESULTS: Eighty-five patients were
      identified as having undergone enucleation. Trauma accounted for 51 cases (60%),
      of which 13 (25%) were caused by air guns, the largest single cause of
      enucleation secondary to trauma. Overall, air gun injuries accounted for 15% of
      enucleation procedures, whereas retinoblastoma accounted for 21%. All air gun
      injuries were in boys (median age 14 years, range 9 to 16 years). Of the 13 eyes
      with air gun injuries 7 had ocular perforation and 6 had ocular penetration. In
      all cases the intraocular structures were severely disrupted. The CHIRPP database
      included 165 air gun injuries; 32 were to the eye or ocular adnexa, resulting in
      26 hospital admissions. CONCLUSIONS: Air guns were the largest single cause of
      enucleation secondary to trauma in our study. These guns are widely available in
      Canada and are unrestricted at muzzle velocities capable of causing death or
      serious injury, especially to the eye. We feel that air guns should be licensed
      only to people aged 16 to 18 years or older and that education in their use
      should be mandatory.

PMID- 7585311
TI  - Field trial of the Otago photoscreener.
AB  - OBJECTIVE: To assess the effectiveness of the Otago photoscreener in detecting
      amblyogenic factors in the general population. DESIGN: Prospective clinical
      trial. SETTING: Suburban school district in Delta, BC. PARTICIPANTS: A total of
      1245 kindergarten children. INTERVENTIONS: Screening for visual defects was done
      with the Otago photoscreener (by a technician) and the regular manual method (by
      a health care aide). A standard ophthalmologic examination was performed by a
      pediatric ophthalmologist and an orthoptist in a random sample of 20% of all
      children with normal results of screening (n = 241) plus all those with abnormal
      results (n = 29). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive
      predictive value, rates of false-negative and false-positive results. RESULTS:
      The Otago screener had higher sensitivity than the manual technique (81% vs.
      33%), especially for strabismus and cataracts. The specificity values of the two
      techniques were 98% and 97% respectively, and the positive predictive values were
      77% and 54% respectively. The manual technique failed to identify 5.8% of
      children with visual defects, compared with 1.6% for the Otago screener.
      CONCLUSIONS: The Otago photoscreener is a superior instrument for identifying
      amblyogenic eye disease. However, given the relatively low yield, the value of
      any screening method should be assessed with regard to both costs and benefits.

PMID- 7585312
TI  - Severe toxic keratopathy secondary to topical anesthetic abuse.
AB  - OBJECTIVE: To describe the clinical findings in three cases of abuse of topically
      administered ophthalmic anesthetics and to review the clinical signs, diagnosis
      and treatment. DESIGN: Case series. SETTING: Two university-affiliated hospitals
      in Montreal. PATIENTS: Three patients with toxic keratopathy due to abuse of
      topically applied anesthetics. RESULTS: The three patients presented with a
      nonhealing epithelial defect, marked stromal edema, folds in Descemet's membrane
      and a typical stromal ring infiltrate. All three required a conjunctival flap,
      and two underwent penetrating keratoplasty. The drugs (0.5% tetracaine and 0.5%
      proparacaine) were easily obtained, at the workplace in two cases and by stealing
      from the ophthalmologist's examining room in the third case. CONCLUSIONS: The
      unrestricted availability of topically applied ophthalmic anesthetics as over-the
      counter medications in Canada must be reevaluated.

PMID- 7585314
TI  - The management of age-related macular degeneration: patterns of referral and
      compliance in seeking low-vision aids.

PMID- 7585313
TI  - Granulomatous reaction to Bowman's layer in herpetic keratitis and band
      keratopathy.
AB  - OBJECTIVE: To characterize granulomatous reactions around Bowman's layer. DESIGN:
      Case series. SETTING: Registry of Ophthalmic Pathology, Armed Forces Institute of
      Pathology, Washington. PATIENTS: All patients with a code for granulomatous
      reactions to Bowman's (membrane) layer or Descemet's membrane. In addition, all
      corneas identified as having elastotic or calcific degeneration of Bowman's layer
      were reexamined to identify a possible granulomatous reaction to Bowman's layer.
      RESULTS: Review of 210 corneal buttons and enucleated eyes yielded eight cases in
      which evidence of a granulomatous reaction to Bowman's layer was present: five
      patients with chronic keratitis, including three with herpetic keratitis
      (disciform in two and ulcerative in one), and three patients whose corneas had
      old degenerative pannus with calcification of Bowman's layer. In the patients
      with chronic keratitis the reaction tended to be focal and accompanied by
      inflammation; in those with degenerative pannus the reaction was diffuse and
      accompanied by minimal inflammation. CONCLUSIONS: Granulomatous reactions to
      Bowman's layer are observed much less frequently than granulomatous reactions to
      Descemet's membrane. Although the pathogenesis of granulomatous reaction to
      Bowman's layer is unclear, a change in the antigenic properties of Bowman's layer
      may be implicated.

PMID- 7585315
TI  - Progressive, refractory keratoconjunctivitis associated with lichen planus.

PMID- 7585316
TI  - Practical application of ultrasound biomicroscopy.
AB  - It is beyond the scope of this article to comment in detail on every condition in
      which ultrasound biomicroscopy has provided useful information. Details of the
      use of this method in clinical conditions are provided in the references cited.
      Ultrasound biomicroscopy has given us a new way of looking at disease in the
      living eye. We can now observe the interrelationships and movement of structures
      that previously could not be imaged. Future theoretic and technologic advances
      should expand the usefulness of this imaging method.

PMID- 7585318
TI  - Vascular alpha-adrenoceptors: from the gene to the human.
AB  - Adrenoceptors can be subdivided into three major types, the alpha 1-, alpha 2-,
      and beta-adrenoceptors. Each of these types can be further subdivided into three
      subtypes, based on pharmacological characteristics. Molecular cloning techniques
      have supported this subclassification. Recent data now suggest that alpha
      adrenoceptor subtypes identified by pharmacological and molecular techniques
      correspond well, although species orthologs of several adrenoceptor subtypes have
      been identified. The secondary structure of the adrenoceptors has been elucidated
      and correlated with their interaction with second messenger molecules. alpha 1
      Adrenoceptors, beta-adrenoceptors, and alpha 2-adrenoceptors mediate their
      actions through stimulation of inositol phosphate release, stimulation of
      adenylate cyclase, and inhibition of adenylate cyclase, respectively. Site
      directed mutagenesis and the preparation of chimeric receptors have located the
      site of receptor--second messenger interaction to the third intracellular loop
      for each of these adrenoceptors. While subtypes of each of these classes all
      interact with the same second messenger, studies with recombinant alpha 2
      adrenoceptors show subtype-related differences in receptor--second messenger
      interaction. Multiple alpha-adrenoceptor subtypes are expressed in vascular
      smooth muscle and are involved in various aspects of blood vessel function,
      including contraction, cellular growth, and proliferation. Various physiological
      factors can selectively influence responses to a particular subtype, and the
      relative roles of each subtype can vary between vascular beds and along an
      individual blood vessel as its caliber changes. Functional studies in blood
      vessels suggest the presence of additional alpha-adrenoceptor subtypes not yet
      identified via molecular techniques. Optimization of the therapeutic profile of
      an alpha-adrenoceptor antagonist may be possible via enhancement of selectivity
      for a particular subtype or by design of a specific profile of affinity for the
      individual subtypes.

PMID- 7585317
TI  - Roles of peptides and other substances in cotransmission from vascular autonomic
      and sensory neurons.
AB  - Blood vessels may be innervated by up to three major classes of neurons:
      sympathetic vasoconstrictor neurons; sympathetic or parasympathetic vasodilator
      neurons; and peripheral fibres of small diameter sensory neurons, which can
      mediate vasodilation. Most vascular neurons utilise multiple transmitters,
      including neuropeptides and small nonpeptides such as ATP or nitric oxide, often
      in addition to noradrenaline or acetylcholine. Subpopulations of each major class
      of vascular neurons innervating different vascular segments may contain different
      combinations of neurotransmitters. Furthermore, the same population of neurons
      can release different cotransmitters in response to different patterns of
      stimulation. In general, peptides mediate slower and more long lasting changes in
      vascular resistance than do nonpeptides. Thus, autonomic and sensory neurons are
      well adapted to produce qualitatively different vascular effects in response to
      different types of afferent input. The major challenge for the future is to
      develop new antagonists for many of the substances colocalised in vascular
      neurons, particularly neuropeptides. These agents will allow us to precisely
      determine the relative roles of multiple cotransmitters, and are likely to
      provide therapeutic agents that can be targeted to specific regions of the
      vasculature.

PMID- 7585319
TI  - Regulation of vascular tone.
AB  - The intimal surface of the blood vessel in vivo is subject to shear stress
      resulting from blood flow, which in most of the circulation, at least at rest, is
      laminar. Turbulence can occur at bifurcations, especially those of the large
      arteries, and where vessels curve significantly. Shear stress is a frictional
      tangential force exerted at the fluid-intimal interface in the long axis of the
      vessel. It is now known that hemodynamic shear stress can influence a large
      variety of biological processes in endothelial cells, which vary from those with
      a short response time, just a few milliseconds, such as the opening of ion
      channels, to those that change over a period of minutes to several hours, for
      example, endocytosis and cytoskeleton rearrangement, and those features that
      alter much more slowly, such as cell shape and stiffness. In addition to these
      types of changes, there are suggestions that flow acting through shear stress may
      be responsible for several basic attributes of the vasculature, including the
      relative size and diameter of the components of a branching vascular system. In
      this symposium on the flow regulation of the blood vessel, the first presentation
      dealt with optimality principles that appear to govern the dimensions of the
      vasculature, in particular the geometry of the arterial branching and the role of
      shear stress. An optimally designed system is one that requires the least
      metabolic work to perform its function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585321
TI  - New aspects of the role of histamine in cardiovascular function: identification,
      characterization, and potential pathophysiological importance of H3 receptors.
AB  - As a result of intensive research during several decades, the distribution,
      function, and pathophysiological role of cardiovascular H1 and H2 receptors are
      well known, whereas reports on the occurrence and function of H3 receptors in
      blood vessels and the heart have not become available before the last 7 years
      (i.e., 4 years after the first description of these receptors in the central
      nervous system in 1983). The development of selective and potent H3 receptor
      agonists and antagonists was a prerequisite for convenient investigations of
      cardiovascular H3 receptors, which like H1 and H2 receptors are G-protein coupled
      but unlike them have not yet been cloned. Both in blood vessels and the heart, H3
      receptors are located on noradrenergic nerve endings and upon stimulation mediate
      an inhibition of noradrenaline release. Whereas it remains to be clarified under
      which conditions the vascular H3 receptors may be stimulated by endogenous
      histamine, those in the heart become activated in the early phases of myocardial
      ischemia characterized by an increased histamine spillover. The H3 receptors in
      the central nervous system also appear to be of importance for the control of
      vascular function. Inhibitory presynaptic H3 receptors occur on trigeminal
      sensory C fibres supplying blood vessels in the dura mater. Release of
      neuropeptides from these fibres induces a neurogenic inflammation, which has been
      suggested to be involved in the pathogenesis of migraine. An interaction,
      involving presynaptic H3 receptors, between sensory C fibres and mast cells in
      close apposition to these fibres plays a role in the control of histamine
      synthesis in the dura mater.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585320
TI  - Regulation of vascular tone: cross-talk between sarcoplasmic reticulum and
      plasmalemma.
AB  - Selected topics on the roles of sarcoplasmic reticulum (SR) in the control of
      vascular smooth muscle (VSM) tone are briefly reviewed with particular reference
      to the regulation of cytosolic concentration of free calcium ions, [Ca2+]i.
      Although morphological evidence and subcellular membrane studies indicate a
      relatively meager quantity of SR in VSM and of endoplasmic reticulum (ER) in
      endothelial cells (ECs) compared with skeletal muscle and cardiac muscle,
      contractility studies suggest that vascular tone is, to a large extent, regulated
      by the intracellular Ca2+ stores in smooth muscle and endothelial cells.
      Cytosolic Ca2+ levels control myosin light chain phosphorylation and contraction
      in VSM and activation of NO synthase and phospholipase A2 in ECs to regulate
      nitric oxide (NO) and prostaglandin I2 formation. Understanding of the importance
      of SR or ER in modulating the [Ca2+]i in VSM and ECs has been further advanced as
      a result of the new development and refinement of biophysical techniques in the
      measurement of cellular Ca2+ concentrations and ion currents, such as fluorescent
      Ca2+ indicators and patch-clamp techniques. Experimental evidence has accumulated
      in support of the existence of cross-talk between SR-ER and the plasma membrane
      (PM). Novel pharmacological tool drugs selective for the SR-ER Ca2+ pump, such as
      thapsigargin and cyclopiazonic acid, as well as for SR-ER Ca2+ channels, such as
      ryanodine (for the Ca(2+)-induced Ca2+ release channel) and inositol
      polyphosphates and heparin (for the inositol-1,4,5-trisphosphate activated Ca2+
      channel), together with the use of blockers for selective PM Ca2+ channels have
      enabled better formulation and elucidation of the mechanisms of cross-talk
      between SR-ER and PM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585322
TI  - Intracellular mechanisms involved in the regulation of vascular smooth muscle
      tone.
AB  - Vascular smooth muscle contraction is thought to occur by a mechanism similar to
      that described for striated muscles, i.e., via a cross-bridge cycling--sliding
      filament mechanism. This symposium focused on Ca2+ signalling and the role of
      intracellular free Ca2+ concentration, [Ca2+]i, in regulating vascular tone: how
      contractile stimuli leading to an increase in [Ca2+]i trigger vasoconstriction
      and how relaxant signals reduce [Ca2+]i causing vasodilation. M.P. Walsh opened
      the symposium with an overview emphasizing the central role of myosin
      phosphorylation-dephosphorylation in the regulation of vascular tone and
      identifying recent developments concerning regulation of [Ca2+]i, Ca2+
      sensitization and desensitization of the contractile response, Ca(2+)-independent
      protein kinase C induced contraction, and direct regulation of cross-bridge
      cycling by the thin filament associated proteins caldesmon and calponin. The
      remainder of the symposium focused on three specific areas related to the
      regulation of vascular tone: Ca2+ signalling in relation to smooth muscle
      structure, structure-function relations of myosin, and the role of cyclic GMP
      (cGMP) dependent protein kinase. G.J. Kargacin described how smooth muscle cells
      are structured and how second messenger signals such as Ca2+ might be modified or
      influenced by this structure. J. Kendrick-Jones then discussed the results of
      mutagenesis studies aimed at understanding how the myosin light chains,
      particularly the phosphorylatable (Ca(2+)-calmodulin dependent) regulatory light
      chains, control myosin. The vasorelaxant effects of signalling molecules such as
      beta-adrenergic agents and nitrovasodilators are mediated by cyclic nucleotide
      dependent protein kinases, leading principally to a reduction in [Ca2+]i. T.M.
      Lincoln described the roles of cyclic nucleotide dependent protein kinases, in
      particular cyclic GMP dependent protein kinase, in vasodilation.

PMID- 7585323
TI  - Pathophysiology of smooth muscle in hypertension.
AB  - Structural changes of the arteries in hypertension are determined by the unique
      genetics of the animals and by various growth promoters and growth inhibitors.
      Vascular smooth muscle cell growth promoting factors include fibroblast growth
      factor, platelet-derived growth factor, and vasoactive peptides such as
      norepinephrine, angiotensin II, and endothelin. Endothelial cells secrete three
      types of growth inhibiting factors. These are heparin--heparan sulfate,
      transforming growth factor beta, and nitric oxide. The effect of sympathetic
      innervation on vascular growth is probably dependent on its interaction with the
      renin-angiotensin system. In the mesenteric vascular bed, the elevated resistance
      in the arterial system is present in both the macroarteries and in the more
      distal microarteries and veins. Changes in resistance arteries include
      hypertrophy and reduction in outer diameter (remodelling). In the resistance
      arteries from human essential hypertensives, remodelling is the predominant
      finding. Long-term treatment with an angiotensin I converting enzyme inhibitor
      but not with a beta-blocker was effective in reversing this type of vascular
      change. Studies have suggested that in addition to angiotensin II, endothelin may
      play a role in vascular remodelling of resistance arteries.

PMID- 7585325
TI  - Pharmacological investigation of signaling mechanisms contributing to phasic and
      tonic components of the contractile response of rat arteries to noradrenaline.
AB  - The mechanisms contributing to the contractile responses to two different
      concentrations of noradrenaline (NA) in rat aorta and mesenteric artery were
      compared using nifedipine, which inhibits calcium influx through dihydropyridine
      sensitive channels, ryanodine, which depletes intracellular calcium stores, and
      calphostin C, which inhibits protein kinase C (PKC). Both submaximal and maximal
      concentrations of NA induced a biphasic response in aorta and mesenteric artery,
      with an early fast phase and a later sustained tonic component. Calcium release
      from intracellular stores contributed to the phasic component of contraction to
      both concentrations of NA in aorta, although to a greater extent to the
      submaximal concentration. In aorta, inhibiting both intracellular calcium release
      and calcium influx through dihydropyridine-sensitive channels simultaneously or
      inhibiting PKC activity alone significantly reduced the tonic response to a
      maximal concentration of NA. However, the tonic response to a submaximal
      concentration of NA in aorta was significantly inhibited only when intracellular
      calcium stores were depleted with ryanodine. In mesenteric artery, the phasic
      response to a maximal concentration of NA was significantly depressed only when
      both calcium influx and intracellular calcium release were inhibited
      simultaneously. However, the phasic response to a submaximal concentration of NA
      was significantly inhibited by blocking calcium influx alone, but not by blocking
      intracellular calcium release alone. The tonic component of the contractile
      response to both concentrations of NA in mesenteric artery appeared to be
      mediated in part by calcium from both intracellular and extracellular
      sources.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585324
TI  - Specific [3H]spiperone binding sites in the pituitary of rainbow trout
      (Oncorhynchus mykiss) and goldfish (Carassius auratus).
AB  - Dopamine, a catecholamine neurohormone, modulates pituitary hormone release in
      teleost fishes and other vertebrates. The existence and binding parameters of a
      pituitary dopamine-neuroleptic receptor from trout were examined and compared
      with those from goldfish. Pituitary homogenate was incubated with [3H]spiperone
      (D2 antagonist) under several experimental paradigms; incubations were terminated
      by filtration and bound 3H radioactivity was assessed by liquid scintillation
      spectroscopy. Specific binding of [3H]spiperone was tissue dependent. Equilibrium
      displacement analyses using domperidone (D2 antagonist) indicated a single class
      of binding site (LIGAND) with Kd = 2.49 +/- 0.89 microM and a capacity of 3.10 +/
      0.45 nmol/mg protein; the goldfish Kd and capacity were both significantly (p <
      0.05) larger: Kd = 4.63 +/- 0.30 microM and capacity = 20.66 +/- 2.03 nmol/mg
      protein. The Kd and capacity for the trout pars distalis (2.45 +/- 0.33 microM
      and 3.27 +/- 0.24 nmol/mg protein, respectively) did not differ significantly (p
      < 0.05) from that of the neurointermediate lobe (2.50 +/- 0.08 microM and 3.58 +/
      0.56 nmol/mg protein, respectively). Dopamine D2 receptor ligands differentially
      displaced [3H]spiperone from the trout pituitary, while D1 ligands, a D4 ligand,
      and a 5-hydroxytryptamine (5HT2) receptor antagonist had only small nonspecific
      effects. Comparison of the trout and goldfish pituitary dopamine-neuroleptic
      receptor indicates conservation of receptor affinity (Kd); however, differences
      in receptor numbers and in the distribution of receptors between the pars
      distalis and neurointermediate lobe in the two species may be due in part to
      species or developmental differences, and may reflect differences in the role(s)
      and degrees of influence of dopamine in these fishes.

PMID- 7585326
TI  - Relationship among sensitivity to adrenaline, plasma corticosterone level, and
      estrous cycle in rats.
AB  - The dose-response curves to the chronotropic effect of adrenaline obtained in
      right atria isolated from female rats indicated an order of increasing
      sensitivity to adrenaline, at the pD2 level, according to the estrous cycle, as
      follows: estrus < or = metestrus < or = diestrus < or = proestrus. Inhibition of
      neuronal and extraneuronal uptake shifted the dose-response curves to adrenaline
      to the left only in right atria isolated from rats during estrus or metestrus.
      Moreover, under these experimental conditions, right atria were subsensitive to
      adrenaline during proestrus, in contrast to metestrus. Plasma corticosterone
      levels were lower during estrus and higher at proestrus. There was a positive
      correlation between right atria sensitivity to adrenaline and plasma
      corticosterone levels and estrous cycle phases. Our results also suggest that in
      the rat atria during proestrus, as opposed to the other phases of the estrous
      cycle, there was an endogenous inhibition of extraneuronal uptake together with
      some alteration at the adrenoceptor level and (or) at intracellular mechanisms
      beyond receptors.

PMID- 7585327
TI  - Actions of diazoxide on CA1 neurons in hippocampal slices from rats.
AB  - Membrane effects of diazoxide (DZX) were examined in CA1 pyramidal neurons,
      mainly by whole-cell recording in slices kept at 33 degrees C (from Sprague
      Dawley rats). Bath applications of DZX (0.65 mM) did not significantly change the
      resting input conductance; but instantaneous inward rectification was reduced by
      47 +/- 14% (near -110 mV). There was a similar depression of a large, sustained
      voltage-dependent outward current (by 44 +/- 11% near 0 mV). A nearly identical
      reduction of the outward current recorded in a Ca current suppressing medium (but
      not in 30 mM tetraethylammonium) indicated that the DZX-sensitive current
      includes the delayed rectifier. In Mn, low-Ca medium containing
      tetraethylammonium and carbachol, DZX potentiated (by 43 +/- 12%) the D-type
      slowly decaying outward current seen after hyperpolarizing pulses at a holding
      potential of approximately -50 mV. DZX abolished or depressed slow inward
      currents, such as the tetrodotoxin-sensitive persistent Na current, high voltage
      activated Ca currents (IC50 = 0.47 mM), and the Q current. In 6 of 13 cells
      recorded with electrodes containing either guanosine or adenosine diphosphate,
      DZX potentiated the voltage-dependent outward current, but input conductances
      were reduced. In conclusion, although there was little indication that it
      activates classical KATP channels in CA1 neurons, DZX strongly depresses several
      voltage-dependent, slowly inactivating outward and inward currents, which are
      important modulators of cell excitability.

PMID- 7585328
TI  - Differential effect of desipramine and 2-hydroxydesipramine on depolarization
      induced calcium uptake in synaptosomes from rat limbic sites.
AB  - This study was conducted to investigate the inhibition of synaptosomal 45Ca
      uptake by desipramine and its major metabolite 2-hydroxydesipramine in the rat
      hippocampus and cingulate cortex, areas associated with emotional control. A
      concentration-dependent inhibition of net depolarization-induced 45Ca uptake was
      observed for desipramine (20-200 microM) in synaptosomes from both sites.
      However, 20 microM 2-hydroxydesipramine failed to inhibit calcium channel
      function in either of the two limbic sites; higher concentrations (60 or 200
      microM) did produce a minor degree of inhibition in hippocampus synaptosomes.
      Others have shown that the clinically encountered plasma concentrations of 2
      hydroxydesipramine are lower than those of desipramine, and the brain
      concentration of 2-hydroxydesipramine is therefore not expected to surpass or
      even reach 20 microM. In view of the previously observed clinical activity of 2
      hydroxydesipramine, the present results indicate that calcium channel antagonism
      may not be the basis for the therapeutic effect of tricyclic antidepressants.

PMID- 7585329
TI  - Hemostatic profile of bovine ovarian follicular fluid.
AB  - The hemostatic profile of bovine ovarian follicular fluid was evaluated and the
      levels of procoagulant, fibrinolytic, and inhibitory activity compared with
      plasma. The results of the prothrombin time assay and the presence of fibrinogen
      along with factor VII and factor X activity indicate that bovine follicular fluid
      possesses components of the "extrinsic" or "tissue factor" coagulation system.
      The absence of factor VIII:C activity, along with the extremely low levels of
      factors IX and XI, indicates that there is not a functional "intrinsic"
      coagulation pathway. The fluid derived from large follicles exhibited increased
      levels of factors VII and X activity and a shorter prothrombin time compared with
      fluid obtained from the less mature small follicles. Similar alterations in the
      levels of the inhibitory proteins antithrombin III and alpha 2-macroglobulin were
      observed. Overall the amount of antithrombin III was similar to that in plasma,
      the levels of fibrinogen and factor X were approximately 2-fold lower, and the
      levels of factor VII and factor X were approximately 10-fold lower than in
      plasma. The fibrinolytic activity in follicular fluid was greater than the
      procoagulant or inhibitory activity. Plasminogen activator activity was 5-fold
      higher, while both plasminogen and antiplasmin values were similar to plasma
      levels.

PMID- 7585331
TI  - Characteristics of tetanic contractions in caffeine-treated rat myocardium.
AB  - Skinned fiber preparations are used to obtain the maximal contractile activation
      of isolated myocardial preparations. Tetanic contractions elicited in the
      presence of sarcoplasmic reticulum inhibitors have also been used as an
      alternative method to produce maximal active tension in the intact myocardium. In
      this work our purpose was to define the best conditions to obtain tetanic
      contractions in the rat myocardium and to compare the influence of muscle length
      and inotropic interventions (Ca2+ and Bay K 8644) in the tension produced in
      twitches and tetanic contractures. Papillary muscles were mounted in a perfusion
      chamber to record isometric force. Tetanic contractions were elicited by using
      suprathreshold stimulation with rectangular pulses (10 ms duration) at 5 Hz in
      the presence of 2.5 mM caffeine. Caffeine depressed the twitch tension but the
      tetanic tension was similar to that produced under steady-state stimulation (0.5
      Hz) in control conditions. Tetanic and twitch tensions were similar along the
      whole extension of the length-tension curve and under the positive inotropic
      effects produced by Ca2+ (0.25 to 3.75 mM) or by the Ca(2+)-channel agonist Bay K
      8644 (1 microM). During long tetanic stimuli (60 s) a time-dependent tension
      decay was observed. This decay was prolonged by reducing the extracellular K+
      from 5.4 to 1.0 microM, suggesting that Ca2+ extrusion through the Na-Ca
      exchanger seems to occur during tetanic stimulation. Since tetanic tension was
      never higher than the tension obtained in twitches elicited at the same Ca2+
      concentration (0.5 Hz), we conclude that tetanic contractures represent a useful
      tool to investigate the contractile response of intact myocardial preparations
      with a nonfunctional sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585330
TI  - Mitochondrial biogenesis during pressure overload induced cardiac hypertrophy in
      adult rats.
AB  - Existing literature provides an equivocal picture of the behavior of
      mitochondrial synthesis during the time course of cardiac hypertrophy. Therefore,
      we examined the effect of cardiac hypertrophy on mitochondrial cytochrome c
      oxidase (CYTOX) activity, the content of CYTOX subunit VIc mRNA, and the
      expression of molecular chaperones. Adult male Sprague-Dawley rats were subjected
      to either abdominal aortic constriction to induce pressure overload (PO) or a
      sham operation (SH). Animals were studied 2, 4, 7, 14, 21, or 28 days after
      surgery. Aortic constriction resulted in a significant evaluation in arterial
      pressure by 4 days after surgery. Significant (p < 0.05) hypertrophy was attained
      by 4 days and was stabilized at 37% between 7 and 28 days. CYTOX activity (U/g)
      did not differ significantly between PO and SH animals at either early (< 7 days)
      or later time points, indicating that mitochondrial content increased in
      proportion to adaptive cellular hypertrophic growth. The concentration of the
      molecular chaperones HSP60 and GRP75 involved in mitochondrial protein import did
      not change with PO treatment. The levels of mRNAs encoding both CYTOX subunit VIc
      and HSP60 remained constant, in proportion to cardiac growth. This suggests that
      the accelerated synthesis of CYTOX and HSP60 during cardiac hypertrophy is
      regulated transcriptionally. The data help to resolve the controversy in the
      literature regarding mitochondrial biogenesis during moderate, stable cardiac
      hypertrophy, and they indirectly indicate that proportional mitochondrial
      synthesis relative to cellular hypertrophy is regulated at the transcriptional
      level.

PMID- 7585332
TI  - Effects of angiotensin II on plasma atrial natriuretic factor in nonpregnant and
      pregnant ewes.
AB  - The release of atrial natriuretic factor (ANF) is primarily determined by atrial
      stretch, but may also be modulated by circulating angiotensin II (AngII). During
      pregnancy, the circulating concentrations of both ANF and AngII are increased. To
      further define possible effects of AngII on ANF release, four doses of AngII
      (0.5, 5, 20, 40 ng.kg-1.min-1) were intravenously infused into five nonpregnant
      and five pregnant (105-140 days of gestation) ewes alone and during the
      simultaneous infusion of sodium nitroprusside at doses sufficient to abolish the
      pressor effects of AngII. Mean arterial pressure (MAP) was increased from 80 +/-
      2 to a maximum of 121 +/- 5 mmHg (1 mmHg = 133.3 Pa) in nonpregnant ewes (p <
      0.01) and from 79 +/- 2 to 116 +/- 4 mmHg in pregnant ewes (p < 0.01) over the
      range of AngII infusion. MAP was unaltered during AngII plus nitroprusside
      infusion, averaging 78 +/- 3 mmHg in nonpregnant ewes and 80 +/- 2 mmHg in
      pregnant ewes. Basal ANF was higher (p < 0.01) in pregnant sheep than in
      nonpregnant sheep. With AngII infusion alone, plasma ANF was increased from 13 +/
      2 to 42 +/- 4 fmol/microL in nonpregnant ewes (p < 0.01) and from 23 +/- 5 to 72
      +/- 16 fmol/microL in pregnant ewes (p < 0.01). However, during AngII plus
      nitroprusside infusion, the increases in plasma ANF observed were completely
      abolished in both nonpregnant and pregnant ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585335
TI  - In vivo pharmacological evaluation of two novel type II (inducible) nitric oxide
      synthase inhibitors.
AB  - Selective type II (inducible) nitric oxide synthase (NOS) inhibitors have several
      potential therapeutic applications, including treatment of sepsis, diabetes, and
      autoimmune diseases. The ability of two novel, selective inhibitors of type II
      NOS, S-ethylisothiourea (EIT) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine
      (AMT), to inhibit type II NOS function in vivo was studied in lipopolysaccharide
      (LPS) treated rats. Type II NOS activity was assessed by measuring changes in
      plasma nitrite and nitrate concentrations ([NOx]). Both EIT and AMT elicited a
      dose-dependent and > 95% inhibition of the LPS-induced increase in plasma [NOx].
      The ED50 values for EIT and AMT were 0.4 and 0.2 mg/kg, respectively. In
      addition, the administration of LPS and either NOS inhibitor resulted in a dose
      dependent increase in animal mortality; neither compound was lethal when
      administered alone. Pretreatment with L-arginine (but not D-arginine) prevented
      the mortality, while not affecting the type II NOS-dependent NO production,
      suggesting the toxicity may be due to inhibition of one of the other NOS isoforms
      (endothelial or neuronal). Thus, although EIT and AMT are potent inhibitors of
      type II NOS function in vivo, type II NOS inhibitors of even greater selectivity
      may need to be developed for therapeutic applications.

PMID- 7585333
TI  - Peripheral vascular smooth muscle responsiveness to tumour-promoting phorbol
      esters in pacing-induced heart failure.
AB  - Contractions of the dorsal pedal artery and saphenous vein to phorbol 12,13
      dibutyrate (PDBu), 12-O-tetradecanoylphorbol 13-acetate (TPA), and 4 alpha
      phorbol 12,13-didecanoate (4 alpha-phorbol) were measured from dogs with and
      without pacing-induced heart failure. The effects of polymyxin B (a relatively
      selective protein kinase C inhibitor), nifedipine (calcium channel blocker), and
      prazosin (alpha 1-adrenoceptor antagonist) were examined on the contractions
      developed to PDBu before heart failure, after 1 week of pacing, and at end-stage
      heart failure. PDBu and TPA, but not 4 alpha-phorbol, produced concentration
      dependent increases in contractile force in both the artery and the vein. In the
      dorsal pedal artery, efficacy of and sensitivity to PDBu and TPA were enhanced
      after 1 week of pacing, but returned to control level at end-stage heart failure.
      In the saphenous vein, the concentration-effect curve to PDBu was displaced to
      the left after 1 week of pacing; EC50 values for PDBu were 3.2 x 10(-9) and 3.2 x
      10(-8) M for 1 week paced and control, respectively. Polymyxin B significantly
      decreased the efficacy of PDBu in the dorsal pedal artery at all time points, but
      was less effective with advancing heart failure. In contrast, in the vein, there
      was a significant increase in inhibitory potential at end-stage heart failure. In
      all cases, nifedipine inhibited PDBu in a concentration-dependent manner. With
      the progression of heart failure, the contractions of the saphenous vein,
      developed to PDBu, became more sensitive to inhibition by nifedipine. Prazosin
      failed to inhibit vascular effects of PDBu. These results are discussed in terms
      of protein kinase C involvement in vascular contractions and its role in the
      pathogenesis of heart failure.

PMID- 7585334
TI  - Direct depressant effect of phosphodiesterase inhibitors on ATPase activity of
      rat cardiac myofibrils.
AB  - The aim of this study was to determine (i) whether phosphodiesterase inhibitors
      influenced ATPase activity of maximally calcium activated cardiac myofibrils and
      (ii) whether this effect varied in relation to isomyosin composition. Myofibrils
      were prepared from ventricular myocardium of 2- to 3-month-old rats. ATPase
      activity was determined at low ionic strength at high (> 7.5) and low (4.4) pCa.
      Five compounds (amrinone, milrinone, enoximone, piroximone, and rolipram) were
      examined at concentrations between 10 microM and 1 mM. The results obtained
      showed that only milrinone and amrinone inhibited ATPase activity; inhibition was
      dose dependent, and milrinone was more potent than amrinone. To assess whether
      isomyosin composition might influence the responsiveness of myofibrils to
      phosphodiesterase inhibitors, the effect of 1 mM milrinone was also determined in
      myofibrils from hypothyroid rats. According to previous observations
      hypothyroidism caused an isomyosin shift from V1 to V3 in rat ventricular
      myocardium. The inhibitory effect of milrinone was lower in myofibrils prepared
      from hypothyroid rats than in myofibrils from euthyroid rats.

PMID- 7585336
TI  - Inhibition of neurons in the rat medial amygdaloid nucleus in vitro by
      somatostatin.
AB  - Effects of somatostatin (SRIF) on neurons in the medial amygdaloid nucleus were
      investigated in rat brain slice preparations, using extracellular recordings.
      Following bath application of SRIF at 10(-7) - 10(-6) M, 63 of 81 (78%) medial
      amygdala neurons showed an inhibitory response. The inhibitory effect of SRIF was
      dose dependent, and the threshold concentration was approximately 10(-9) M. The
      inhibitory response to SRIF persisted during synaptic blockade in two-thirds of
      neurons tested. The inhibitory effect of SRIF was reduced by picrotoxin, a GABAA
      receptor antagonist, in one-third of neurons. These results suggest that SRIF
      exerts an inhibitory effect on medial amygdala neurons through either a direct
      action on SRIF receptors or a GABAergic synaptic involvement.

PMID- 7585337
TI  - The 1994 Stevenson Award Lecture. Follicle-stimulating hormone and luteinizing
      hormone: a tale of two gonadotropins.
AB  - Although most gonadotropes synthesize both luteinizing hormone and follicle
      stimulating hormone, the transcription, content, and secretion rates of the two
      gonadotropins can be separated. The signals external to the gonadotropic cells
      that appear to be important in the differential regulation are gonadotropin
      releasing hormone pulse frequency (high pulse frequency favors luteinizing
      hormone), steroid feedback (works on both but induces a more powerful negative
      feedback on luteinizing hormone), and gonadal peptide feedback (activin increases
      follicle-stimulating hormone; inhibin and follistatin decrease it). We know very
      little about the pathways within the gonadotropes that favor one gonadotropin
      rather than another. It is expected that the cloning of the genes for both
      gonadotropins and the use of specific cell lines and transfections will lead to
      elucidation of these pathways.

PMID- 7585338
TI  - Ontogeny of 2-[125I]iodomelatonin binding sites in the chicken (Gallus
      domesticus) kidney and spleen.
AB  - To understand the possible role of melatonin receptors in the development of
      renal and immune functions, age-related variations of 2-[125I]iodomelatonin
      binding sites in the chicken kidney and spleen were investigated by radioreceptor
      assay. Chickens at embryonic day 20, as well as 2 days, 9 days, 2 weeks, 6 weeks,
      12 weeks, and 16 weeks after hatching, were kept under a 12 h light:12 h dark
      photoperiod and killed at the middle of the light period. Binding sites for 2
      [125I]iodomelatonin in membrane preparations of the chicken kidney and spleen
      were present on embryonic day 20. The maximum binding densities (Bmax) in the
      kidney increased to a peak between 9 days and 2 weeks of age, then progressively
      decreased. Bmax values of 2-[125I]iodomelatonin binding sites in the chicken
      spleen were lower than in the kidney. The peak density in the chicken spleen was
      recorded at day 2 after hatching and decreased significantly after 6 weeks of
      age. There were no significant differences in binding affinities (Kd) in kidney
      and spleen of chicken in the different age groups studied. The unity of Hill
      coefficients of 2-[125I]iodomelatonin binding sites of the chicken kidney and
      spleen in all age groups tested suggested that only a single class of binding
      sites was present in these tissues during development. It is proposed that the
      developmental changes in 2-[125I]iodomelatonin binding sites in the chicken
      kidney and spleen may be pertinent to the development of diurnal rhythms of
      kidney functions and the post-pubertal decline in immune functions of the
      chicken.

PMID- 7585340
TI  - Exposure to ionizing radiation alters vasoreactivity in rat jejunum ex vivo.
AB  - The effect of ionizing radiation on jejunal blood flow was investigated in rats
      receiving whole-body exposure to 10 Gy gamma-radiation. Irradiation resulted in
      increased myeloperoxidase activity, indicative of neutrophil infiltration, and
      prostaglandin E2 synthesis by 2 h post-irradiation, but had no effect on
      leukotriene B4 synthesis. In ex vivo intestinal chamber studies, exposure to
      radiation reversed the mucosal-submucosal blood flow changes elicited by
      intravenous administration of leukotriene C4 (1 microgram.kg-1.min-1 for 10 min)
      or endothelin 1 (1 microgram.kg-1.min-1 for 5 min), but not that elicited by
      topical capsaicin (100 or 640 microM), as measured by laser Doppler flowmetry.
      The effect of radiation on vascular responses to leukotriene C4, but not those to
      endothelin 1, was reversed by pretreatment of the rats with the cyclooxygenase
      inhibitor, indomethacin (5 mg/kg). There was no significant effect of irradiation
      on mean arterial pressure or on ion or protein effluxes into the chamber bathing
      solution, nor did irradiation alter transmural potential difference. These
      studies point to altered responsiveness of the jejunal mucosal-submucosal
      vasculature shortly after exposure to ionizing radiation. Changes in function
      could reflect the onset of an acute inflammatory response, and appear to have
      cyclooxygenase-dependent and -independent components.

PMID- 7585341
TI  - Baclofen-induced block of the Hering-Breuer expiratory-promoting reflex in rats.
AB  - Baclofen, a gamma-aminobutyric acid (GABA) agonist acting on GABAB receptors, has
      profound effects on respiratory function. We tested a hypothesis that GABAB
      receptors are involved in modulation of the respiratory reflexes mediated by
      pulmonary slowly adapting stretch receptors. Urethane-anesthetized (1.2-1.6 g/kg;
      i.p.) Wistar rats with body weight 230-320 g were breathing room air supplemented
      with oxygen. The gas mixture was applied to the T-shaped tracheal cannula at a
      flow rate of 1.5 L/min. The head of the animals was mounted in a stereotaxic
      apparatus, and the medulla was exposed. We recorded integrated diaphragmatic EMG
      (Di) and tracheal and arterial blood pressures. Injections of 100 nL of saline
      into the nucleus tractus solitarii (NTS) preceded injections of 60 or 110 pmol
      baclofen in group 1 (n = 14), and 2.8 nmol CGP 35348, a GABAB receptor
      antagonist, in group 2 (n = 5). Saline had no effects on baseline Di. Occlusion
      of the tracheal cannula caused an increase in tracheal pressure to 8 cmH2O (1
      cmH2O = 98.1 Pa) and provoked a prolongation of expiration (the Hering-Breuer
      expiratory-promoting reflex) in all drug-free rats. Baclofen abolished the Hering
      Breuer reflex in all rats. CGP 35348 reversed the block of the reflex. In group
      2, CGP 35348 prevented the effects of baclofen, and alone did not affect
      respiration. These results support our hypothesis and suggest that GABAB
      receptors are present on the medullary pathway of slowly adapting mechanoreceptor
      input. However, GABAB receptors in the rat NTS may not be involved in modulation
      of the fundamental respiratory function.

PMID- 7585339
TI  - Role of nitric oxide and prostaglandins in the regulation of blood pressure in
      conscious rats.
AB  - The present study was designed to investigate the possible role of endothelium
      derived vasodilators, nitric oxide and prostaglandins, in the regulation of blood
      pressure during the presence and absence of the major pressor systems. Conscious
      rats were infused with a cocktail of inhibitors of the sympathetic nervous
      system, renin-angiotensin system, and V1 vascular receptor to vasopressin
      (achieved with hexamethonium, captopril, phentolamine, propranolol, and the V1
      vasopressin (AVP) antagonist des-(CH2)5Tyr(Me)-AVP). The cocktail of
      vasoconstrictor inhibitors induced a marked fall of mean arterial pressure (MAP)
      from 109 +/- 2 to 52 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 24). In animals with
      blockade, the specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginine
      methyl ester (L-NAME), induced a significant increase of MAP from 51 +/- 1 to 84
      +/- 2 mmHg (n = 6). In the presence of indomethacin, a cyclooxygenase inhibitor,
      the pressor response to L-NAME was from 52 +/- 2 to 126 +/- 4 mmHg (n = 6).
      Neither indomethacin (n = 6) nor vehicle (n = 6) alone altered MAP. In intact
      animals without blockade, L-NAME caused a similar increase of MAP when it was
      injected alone (from 107 +/- 3 to 144 +/- 4 mmHg, n = 7) or with indomethacin
      (from 113 +/- 3 to 144 +/- 3, n = 6). Indomethacin alone (n = 8) did not change
      MAP. In conclusion, in the absence of the major pressor systems, the pressor
      effect of the inhibition of the production of endogenous nitric oxide and
      vasodilator prostanoid synthesis appears to be synergistic. These results suggest
      that these two endogenous vasodilators are involved in the maintenance of blood
      pressure.

PMID- 7585342
TI  - Effects of propofol and thiopentone on picrotoxin convulsive threshold in the
      rabbit.
AB  - The purpose of the present study was to examine the effect of intravenous
      administration of propofol and thiopentone on picrotoxin-induced seizures using
      the picrotoxin convulsive threshold test in the rabbit. Neither propofol nor
      thiopentone at a dose of 1.25 mg/kg had any significant effect on picrotoxin
      seizure threshold. However, at higher doses (2.5, 5, 10 mg/kg) both propofol and
      thiopentone produced a significant and dose-dependent increase in the picrotoxin
      convulsive threshold. These findings suggest that propofol is an effective
      anticonvulsant against picrotoxin-induced seizures in the rabbit.

PMID- 7585343
TI  - Similar distribution of trans fatty acid isomers in partially hydrogenated
      vegetable oils and adipose tissue of Canadians.
AB  - The objective of this study was to evaluate the composition of trans fatty acids
      in the subcutaneous fat of Canadians relative to the composition of dietary
      sources of trans fatty acids. The fatty acid composition, total trans acid
      content, and the geometric and positional isomer distribution of unsaturated
      fatty acids of subcutaneous adipose tissue of Canadians were determined using a
      combination of capillary gas-liquid chromatography and silver nitrate thin-layer
      chromatography. The mean total trans fatty acid content was 6.80% at the
      abdominal site and 5.80% at the lateral thigh site. Total trans isomers of
      linoleic acid (18:2n-6) were present at 1.17% in abdominal and 1.59% in thigh
      adipose tissue, with 9c.12t-18:2 being the most prevalent isomer followed by 9c
      13t-18:2 and 9t,12c,-18:2. The oleic acid (18:1) trans isomer distribution in
      adipose tissue differed from that in butter fat, but it was similar to that in
      partially hydrogenated vegetable oils. The reverse was true for the 18:1 cis
      isomers. Total 18:1 trans isomers were inversely related to 18:2n-6 content in
      adipose tissue, suggesting the trans fatty acid intake is inversely related to
      the intake of linoleic acid. Partially hydrogenated vegetable oils appear to be
      the major source of trans fatty acids in adipose tissue of Canadians.

PMID- 7585344
TI  - Interaction between calcium and zinc on L-threonine absorption in rabbit jejunum.
AB  - The essential minerals calcium and zinc serve unique functions in higher
      organisms, and it is well recognized that homeostatic mechanisms are involved in
      regulating their metabolism. However, it has been reported that zinc, at higher
      concentrations (1 mM), inhibits intestinal absorption of sugars and amino acids.
      The aim of the present work was to determine whether the inhibitory effect on L
      threonine absorption across the rabbit jejunum could be modified by calcium. In
      media with Ca2+, zinc significantly reduced L-threonine absorption. In Ca(2+)
      free media, where calcium chloride was omitted and replaced isotonically with
      choline chloride, the amino acid transport was not modified by zinc, but when
      calcium chloride was replaced isotonically with magnesium chloride, the
      inhibition was observed. Verapamil (blocking mainly Ca2+ transport) did not
      modify the inhibitory effect of zinc on L-threonine transport. When A23187
      (Ca(2+)-specific ionophore) was added in media with and without Ca2+, zinc
      produced no change in L-threonine transport. These results suggest that calcium
      and zinc could have an affinity with the same chemical groups of the enterocyte
      membrane, which would be related to the intestinal absorption of amino acids.

PMID- 7585345
TI  - Myocardial metabolic and functional responses to acetylcholine are altered in
      thyroxine-induced cardiac hypertrophy.
AB  - We tested the hypothesis that acetylcholine would reduce myocardial O2
      consumption and function, and that thyroxine (T4, 0.5 mg/kg for 16 days) induced
      cardiac hypertrophy would change this relationship. Anesthetized open-chest New
      Zealand white rabbits were divided into four groups: control-vehicle (CV, n = 8),
      control-acetylcholine (CA, n = 10), T4-vehicle (T4V, n = 9), and T4-acetylcholine
      (T4A, n = 10). Either vehicle or acetylcholine (10(-3) M) was topically applied
      to the left ventricular surface. Coronary blood flow (radioactive microspheres)
      and O2 extraction (microspectrophotometry) were used to determine O2 consumption,
      and muscarinic receptor density and affinity were also determined. T4 increased
      the heart weight/body weight ratio from 2.6 +/- 0.1 to 3.4 +/- 0.1. T4-treated
      animals had higher heart rates, blood pressures, and left ventricular dP/dtmax
      than control rabbits. Topical acetylcholine depressed hemodynamic parameters with
      a greater decrement in pressures and cardiac output in the T4A group (CA, -25%,
      T4A, -40%). Myocardial O2 consumption and coronary blood flow were higher in the
      T4-treated hearts. Myocardial O2 consumption significantly declined in both
      groups during acetylcholine, but the reduction was greater in the T4-treated
      hearts (CV 7.9 +/- 0.4 to CA 5.8 +/- 0.6 and T4V 18.8 +/- 3.0 to T4A 7.3 +/- 1.0
      mL O2.min-1.100 g-1). Muscarinic receptor density (Bmax) was elevated by 41% in
      the T4-treated hearts, but affinity (Kd) was not altered. Thus, the T4-treated
      hearts responded to acetylcholine to a greater extent than control hearts in
      terms of functional and O2 consumption decrements.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7585346
TI  - Endothelial cell products alter mammalian skeletal muscle function in vitro.
AB  - We tested the hypothesis that endothelin and nitric oxide (NO) alter the force
      developed by fast-twitch and slow-twitch mammalian skeletal muscle, using a mouse
      skeletal muscle preparation trimmed to approximately 50% of the original diameter
      to decrease diffusion distances. We suspended trimmed soleus (SOL) and extensor
      digitorum longus (EDL) muscles in Krebs-Henseleit buffer (27 degrees C; pH 7.4)
      gassed with 95% O2 -5% CO2. Muscles were stimulated once every 90 s for 500 ms at
      50 Hz for SOL and 100 Hz for EDL. The force developed by trimmed SOL was 223.8 +/
      9.1 mN/mm2 and by EDL was 247.3 +/- 9.4 mN/mm2. Endothelin 1 (ET-1) had no
      effect on EDL but significantly accelerated the rate of decrease of developed
      force of SOL at concentrations of 10(-10) mol/L and higher within 10
      contractions. When ET-1 was removed, force returned toward control value.
      Endothelin 3 (ET-3) had no effect on either muscle. S-Nitroso-N
      acetylpenicillamine (SNAP), a source of NO, increased developed force over time
      in both muscles, with a threshold of 10(-6) mol/L. The effect was evident within
      5 contractions in both muscles. Force remained elevated above control values
      after the removal of SNAP. Thus ET-1 attenuated and NO amplified mammalian
      skeletal muscle function.

PMID- 7585347
TI  - Characterization of the vasorelaxant activity of tyramine and other
      phenylethylamines in rat aorta.
AB  - We recently reported that tyramine caused concentration-dependent relaxation of
      rat aorta, which was endothelium independent and was not exerted via alpha 1
      adrenoceptors (AR), alpha 2AR, beta 1AR, beta 2AR, or receptors for 5
      hydroxytryptamine, histamine, and adenosine. The present studies were done on
      endothelium-denuded strips to determine structure-vasorelaxant activity after
      blockade of beta AR by propranolol plus irreversible blockade of alpha 1AR with
      benextramine. Vasorelaxation under these conditions was limited to
      noncatecholamines, and their vasorelaxant potencies were methoxyphenamine >
      tyramine > p-hydroxyephedrine > L-amphetamine > L-ephedrine > phenylethylamine >
      synephrine > methoxamine > octopamine. beta 3AR agonists (BRL 37344 and CGP
      12177A) did not produce vasorelaxation, although tyramine could compete for
      cyanopindolol binding to murine L cells expressing human beta 2AR or beta 3AR.
      There was no significant specific binding of [3H]tyramine to aortic membrane
      preparations after the inhibition of monamine oxidase. Yohimbine, which has a
      high affinity for Drosophila tyramine receptors, also caused dose-dependent
      vasorelaxation like tyramine. It is concluded that tyramine and several other
      phenylethylamines produce relaxation of rat aorta, which does not involve any of
      the known adrenoceptors but may be exerted via novel tyramine receptors.

PMID- 7585348
TI  - Ethics for working with communities of Indigenous Peoples.
AB  - Specific ethical guidelines for working with Indigenous Peoples have been adopted
      by several research institutions. Ethical principles aim at promoting cooperation
      and mutual respect between researchers and communities of Indigenous Peoples.
      These principles are meant to be continually assessed. This article reports on
      the content and format of current ethical guidelines and highlights directions
      for further development.

PMID- 7585349
TI  - Current status of nutritional deficiencies in Canadian aboriginal people.
AB  - Since the Nutrition Canada Survey (1973) there has been clear evidence that
      Aboriginal people have low intakes of many nutrients such as iron, vitamin D,
      calcium, folate, vitamin A, and fluoride. Recent surveys suggest that the
      situation has not changed. Children are most likely to be affected clinically.
      More than half of Aboriginal children in some subpopulations in Manitoba suffer a
      period of iron deficiency, which may affect development. Nutritional rickets is
      still a common problem in Manitoba. We have seen cases of megaloblastic anemia
      due to folate deficiency. The relationship of the well-described low folate
      intake in pregnancy and birth defects has received no attention for the
      Aboriginal population. In a recent survey of Inuit children, dental caries of the
      primary teeth were present in over 70% of children, with a mean DMF (decayed,
      missing, and filled) index of 1.8 teeth in children under 2 and 9.5 in children 6
      to 8 years. Although clinical vitamin A deficiency is not seen, there is now good
      evidence that subclinical deficiency increases susceptibility to infections.
      Although not all Aboriginal populations suffer all of these deficiencies, the
      problems are sufficiently widespread to suggest this is an urgent problem. It
      will not be solved simply by education. There must be a political will and a
      coordinated effort to make a balanced diet available to all at an affordable
      cost.

PMID- 7585350
TI  - Evaluating food use by Canadian aboriginal peoples.
AB  - Canadian Aboriginal people encompass diverse cultural groups, whose daily food
      patterns vary in regard to the kinds and proportions of indigenous foods.
      Standard dietary methods of assessing food consumption sometimes require
      modification to be understandable and acceptable to Aboriginal communities.
      Depending upon the purpose of the research, food frequency methods, repeated 24-h
      recalls of individual food consumption, and (or) examination of food preferences
      and food health beliefs may be used. Consultation with Aboriginal community
      leaders in planning the research is essential, to ensure collaboration and
      support. Explaining the purpose and methods to community members requires
      assistance of a respected local Aboriginal person, fluent in the language. Extra
      time is required for becoming acquainted with local foods, for translation, and
      for training community members as interviewers. Examples of these principles are
      discussed from the author's experience in the Yukon, the Northwest Territories,
      and northern Alberta.

PMID- 7585351
TI  - Benefits and risks of traditional food for Indigenous Peoples: focus on dietary
      intakes of Arctic men.
AB  - A variety of community and external pressures on Indigenous Peoples are leading
      to increased use of food that is available through industrialization and market
      economics; food in traditional food systems derived from local, natural
      environments is declining in use. This report focusses on dietary intake of
      Arctic men. While nutrient density of Arctic traditional food systems is superior
      to that of the composite of market food consumed in the North, the percentage of
      men's daily energy derived from market food is more than double that from
      traditional food in some communities. Older members of communities consume more
      traditional food than younger members; men consume more traditional food than do
      women. In addition to providing excellent nutrition and opportunities for
      physical exercise. Indigenous Peoples identify many sociocultural benefits to the
      harvest and use of traditional food. Evaluation of environmental accumulation of
      organochlorines in wildlife animal food species shows that risk of organochlorine
      consumption is higher in food systems containing sea mammals, and that tolerance
      levels for some organochlorines may be exceeded.

PMID- 7585352
TI  - Killer activity of yeasts isolated from the water environment.
AB  - The killer activity of 46 strains belonging to 12 yeast and yeast-like species
      isolated from water or sediment samples was studied. Only two strains of the
      genus Cryptococcus did not show killer activity. Killer activity of yeast-like
      species Aureobasidium pullulans, Hyphopichia burtonii and Geotrichum candidum,
      and yeast species Candida krusei and Candida lambica was low. Sporobolomyces
      salmonicolor, Cryptococcus laurentii and Cryptococcus albidus had better activity
      against basidiomycetous than ascomycetous species. Hansenula anomala strains
      showed good activity against Geotrichum candidum strains, Cryptococcus albidus,
      and Sporobolomyces salmonicolor. Rhodotorula species showed activity against the
      majority of both ascomycetous and basidiomycetous species.

PMID- 7585353
TI  - Sequential enrichment of microbial populations exhibiting enhanced biodegradation
      of crude oil.
AB  - The distribution of oil-degrading bacteria in the coastal water and sediments of
      Hokkaido, Japan, was surveyed. The potential of mixed microbial populations to
      degrade weathered crude oil was not confined to any ecological components (water
      or sediment) nor to the sampling stations. One microbial culture that was stable
      during repeated subculturing degraded 45% of the saturates and 20% of the
      aromatics present in crude oil in 10 days during the initial screening. The
      residual hydrocarbons in this culture were extracted by chloroform and dispersed
      in a fresh seawater-based medium and subsequently inoculated with microorganisms
      from the first culture. After full growth of the second culture, the residual
      hydrocarbons were again extracted and dispersed in a fresh medium in which
      microorganisms from the second culture had been inoculated. This sequential
      process was carried out six times to enrich those microorganisms that grew on the
      recalcitrant components of crude oil. After repeated exposure of the residual
      crude oil to the enriched microorganisms, about 80% of the initially added crude
      oil was degraded. The cultures obtained after each enrichment cycle were kept,
      and the degradation of fresh crude oil by the enriched microorganisms was
      examined. The degradative activity of the enriched cultures increased as the
      number of enrichment cycles increased. A microbial population that had been
      selected six times on the residual crude oil could degrade 70% of the saturates
      and 30% of the aromatics of crude oil. Thus, growth of a microbial population on
      residual crude oil improved its ability to biodegrade crude oil.

PMID- 7585354
TI  - Low temperature growth, freezing survival, and production of antifreeze protein
      by the plant growth promoting rhizobacterium Pseudomonas putida GR12-2.
AB  - The plant growth promoting rhizobacterium Pseudomonas putida GR12-2 was
      originally isolated from the rhizosphere of plants growing in the Canadian High
      Arctic. Here we report that this bacterium was able to grow and promote root
      elongation of both spring and winter canola at 5 degrees C, a temperature at
      which only a relatively small number of bacteria are able to proliferate and
      function. In addition, the bacterium survived exposure to freezing temperatures,
      i.e., -20 and -50 degrees C. In an effort to determine the mechanistic basis for
      this behaviour, it was discovered that following growth at 5 degrees C, P. putida
      GR12-2 synthesized and secreted to the growth medium a protein with antifreeze
      activity. Analysis of the spent growth medium, following concentration by
      ultrafiltration, by SDS-polyacrylamide gel electrophoresis revealed the presence
      of one major protein with a molecular mass of approximately 32-34 kDa and a
      number of minor proteins. However, at this point it is not known which of these
      proteins contains the antifreeze activity.

PMID- 7585355
TI  - Weak acid effects and fluoride inhibition of glycolysis by Streptococcus mutans
      GS-5.
AB  - Fluoride and a variety of other weak acids acted to reduce reversibily the acid
      tolerance of glycolysis by intact cells of Streptococcus mutans GS-5 as shown by
      higher final pH values in acid-drop experiments with glucose in excess. The order
      of effectiveness was fluoride > indomethacin > ibuprofen > ketoprofen >
      salicylate > sorbate > cinnamate > p-hydroxybenzoate > benzoate > ascorbate. Only
      fluoride also acted as an inhibitor of the glycolytic enzyme enolase. However,
      enolase in permeabilized cells was also inhibited by acidification with a sharp
      drop-off in activity between pH 6 and 5. It was proposed that the weak acids,
      including fluoride, acted to reduce glycolytic acid tolerance by enhancing
      cytoplasmic acidification and thereby inhibiting enzymes such as enolase. The
      potencies of the acids could not be predicted accurately from knowledge of pKa
      values, octanol-water partition coefficients, and molecular weights. It was
      concluded that their modes of action in acid sensitization involved perturbations
      of membrane function in addition to their acting as transmembrane carriers of
      protons. Methylparaben (methyl ester of p-hydroxybenzoate) was also a sensitizer
      but was less effective than the parent acid.

PMID- 7585356
TI  - Distribution of the streptomycin-resistance transposon Tn5393 among phylloplane
      and soil bacteria from managed agricultural habitats.
AB  - The distribution of the strA-strB streptomycin-resistance (Smr) genes associated
      with Tn5393 was examined in bacteria isolated from the phylloplane and soil of
      ornamental pear and tomato. Two ornamental pear nurseries received previous
      foliar applications of streptomycin, whereas the tomato fields had no prior
      exposure to streptomycin bactericides. Although the recovery of culturable Smr
      bacteria was generally higher from soil, the highest occurrence of Smr was
      observed in phylloplane bacteria of an ornamental pear nursery that received 15
      annual applications of streptomycin during the previous 2 years. Twenty-two and
      12% of 143 Gram-negative phylloplane and 163 Gram-negative soil isolates,
      respectively, contained sequences that hybridized to probes specific for the strA
      strB Smr genes and for the transposase and resolvase genes of Tn5393. These
      sequences were located on large plasmids (> 60 kb) in 74% of the isolates. The 77
      Smr Gram-positive bacteria isolated in the present study showed no homology to
      the Tn5393-derived probes. Although the repeated use of a single antibiotic in
      clinical situations is known to favor the development of strains with resistance
      to other antibiotics, we found no evidence that intensive streptomycin usage in
      agricultural habitats favors the development of resistance to tetracycline, an
      antibiotic also registered for disease control on plants. The detection of Tn5393
      in bacteria with no prior exposure to streptomycin suggests that this transposon
      is indigenous to both phylloplane and soil microbial communities.

PMID- 7585358
TI  - Analysis of sewage effluent for human immunodeficiency virus (HIV) using
      infectivity assay and reverse transcriptase polymerase chain reaction.
AB  - Environmental survival of human immunodeficiency virus type 1 (HIV-1) is an
      important public health concern. Survival of HIV in waste water is of particular
      interest to those who work at treatment facilities and to the general public who
      have contact with rivers or ocean water receiving treated sewage effluent. Other
      researchers have reported that HIV can be detected in waste water. Their studies,
      however, detected homologous nucleic acid sequences but did not attempt to
      determine infectivity. The current study tested primary and secondary effluent
      from a major metropolitan sewage agency for the presence of HIV-1 using reverse
      transcriptase polymerase chain reaction (RT-PCR), HIV-1 p24 antigen enzyme-linked
      immunosorbent assay, and infectivity testing. For RT-PCR, primers SK38/SK39 and
      M667/AA55 were used to identify HIV-1 RNA sequences from concentrated and
      extracted sewage samples. Infectivity assays employed donor peripheral blood
      mononuclear cells (PBMCs) stimulated with phytohemagglutinin. Coxsackievirus B4,
      echovirus 7, and poliovirus 1, enteroviruses normally present in sewage, were
      tested for replication in PBMCs. Poliovirus 1 was found to infect the PBMCs. To
      eliminate other enteroviruses that may also infect the PBMCs and interfere with
      HIV-1 testing, concentrated sewage was treated with human immunoglobulin (free of
      HIV antibodies) and poliovirus antisera before infectivity assays were performed.
      All treated sewage samples tested negative for HIV-1 by all methods used. HIV-1
      seeded into sewage, however, remained infectious in the assay, indicating that
      the sewage water sample did not interfere with HIV infectivity nor was it toxic
      to the PBMCs.

PMID- 7585357
TI  - Regulation of valine catabolism by ammonium in Streptomyces ambofaciens, producer
      of spiramycin.
AB  - In Streptomyces ambofaciens, valine favored spiramycin biosynthesis by supplying
      aglycone precursors. The kinetics of valine consumption and isobutyrate
      production showed that isobutyrate accumulated in the cell during the growth
      phase, was excreted in the stationary phase, and then was reassimilated during
      spiramycin production. When valine was in excess, its deamination led to high
      ammonium excretion and to a significant drop in spiramycin production. We
      demonstrated that ammonium ions were the cause of the negative effect. Addition
      of a chelator agent, Ca3(PO4)2, improved spiramycin production by sixfold. In
      contrast, addition of ammonium, between 0 and 48 h, severely reduced spiramycin
      production. The negative effect of ammonium was reversed by addition of a
      catabolic intermediate of valine, isobutyrate. In addition to stimulating the
      specific growth rate, ammonium ions slowed down valine catabolism: the specific
      valine uptake rate, excretion, and reassimilation of isobutyrate were lowered by
      the pulse of ammonium. Our study showed that in addition to valine dehydrogenase,
      which provided the nitrogen necessary to the cell, ammonium ions repressed
      ketoisovalerate dehydrogenase, which introduced valine as carbon, energy, and
      aglycone precursor sources. However, valine dehydrogenase and ketoisovalerate
      dehydrogenase did not constitute the principal enzymatic targets of the negative
      effect of ammonium in spiramycin production.

PMID- 7585360
TI  - Characterization of diacetin B, a bacteriocin from Lactococcus lactis subsp.
      lactis bv. diacetylactis UL720.
AB  - Fourteen Lactococcus lactis strains showing inhibitory activity against Listeria
      innocua SICC 4202 were isolated from different French raw milks and raw milk
      cheeses and screened for bacteriocin production by the triple layer method under
      conditions that eliminate the effects of lactic acid and hydrogen peroxide. Three
      bacteriocinogenic strains (two Lactococcus lactis subsp. lactis bv. diacetylactis
      UL719 and UL720 and one Lactococcus lactis subsp. lactis UL730) were selected for
      their high capacity to inhibit the growth of various food pathogens, including
      Listeria monocytogenes, Staphylococcus aureus, and clostridial strains. The
      inhibitory compounds from these three strains are inactivated by selected
      proteases, indicating their protein nature. They retained their antibacterial
      activity after heat treatments of 100 degrees C for 60 min and 121 degrees C for
      20 min, and in the pH range from 2 to 11. The bacteriocin diacetin B produced by
      strain UL720 has been purified by a pH-dependent adsorption-desorption procedure,
      followed by reverse-phase high performance liquid chromatography, with a yield of
      1.25% of the original activity. Mass spectrometry analysis indicates that the
      pure peptide has a molecular mass of 4292.32 or 4490.28 Da, while amino acid
      sequencing allowed the identification of the primary structure of the bacteriocin
      composed of 37 amino acid residues. The structure of the peptide did not show
      similarity with other known bacteriocins from lactic acid bacteria.

PMID- 7585361
TI  - Subtyping of Legionella pneumophila isolates by arbitrarily primed polymerase
      chain reaction.
AB  - Arbitrarily primed polymerase chain reaction (AP-PCR) was used to differentiate
      strains of Legionella pneumophila isolated from different water sources in a
      resort hotel in Benidorm, Alicante, Spain, where an outbreak of Legionnaires'
      disease occurred among a group of tourists between 65 and 80 years of age. All
      isolates were L. pneumophila serogroup 1, subtype Pontiac (Knoxville 1). Five
      different patterns (P1 to P5) were obtained by AP-PCR. The number of bands per
      pattern varied between 4 and 11. Patterns P1 and P2 represented 60 and 20% of L.
      pneumophila isolates, respectively. Since different subpopulations of L.
      pneumophila coexisted (up to three different AP-PCR patterns were identified in a
      single room), it was not possible to link an individual L. pneumophila strain to
      the occurrence of this outbreak.

PMID- 7585359
TI  - Detection of Rhizobium meliloti cells in field soil and nodules by polymerase
      chain reaction.
AB  - A genetically marked Rhizobium meliloti strain, R692, was prepared by insertion
      of a 1.7-kb DNA segment from Tn903 between the nifHDK and fixABC genes in the nod
      megaplasmid. This DNA was used as a marker, detectable by polymerase chain
      reaction (PCR), for the specific identification of bacteria in soil samples and
      alfalfa nodules. This detection technique was tested by applying different titres
      of the marked strain to field plots seeded with alfalfa. Samples of soil and
      nodules were assayed for the presence of the marker DNA fragment by PCR using
      primers specific to the marker sequence. The experiments revealed that the
      bacteria could be detected directly in soil containing about 10(3)-10(4)
      bacteria/g, but greater sensitivity was prevented by potent PCR inhibitors
      present in the samples. The titre of the bacteria in the soil decreased rapidly
      after inoculation, dropping about 10-fold per week. Tests of vertical location of
      the bacteria in soil cores showed that the bacteria were initially dispersed to a
      depth of 18 cm, and subsequently retained viability in the top 2-8 cm. As few as
      10 marked R. meliloti per gram of soil resulted in its establishment at
      detectable levels in nodules. Application of about 10(4)-10(5) bacteria/g soil
      was sufficient to give the maximum number of nodules per plant and resulted in 70
      90% occupancy by the marked strain. Limited movement of the inoculant was
      detected by analysis of nodules from plants adjacent to the sites where the
      bacteria were applied, probably by movement in water. The experiments
      demonstrated the advantages of PCR for the monitoring of marked microorganisms in
      the environment.

PMID- 7585364
TI  - Counselling patients before death: support for their decisions.

PMID- 7585362
TI  - The two overlapping Azospirillum brasilense upstream activator sequences have
      differential effects on nifH promoter activity.
AB  - The Azospirillum brasilense nifH promoter is positively controlled by the NifA
      protein bound to the upstream activator sequences (UASs). Two overlapping UASs
      located at -191 and -182 were identified with the consensus TGT-N10-ACA motif.
      The role of the two UASs of Azospirillum brasilense nifH promoter was examined by
      introducing base substitutions in the NifA binding sites. Both the promoter down
      phenotype of a mutation in UAS2 and increased activation when UAS1 was mutated
      reveal that the integrity of the UAS2 is required for the efficient activation of
      nifH promoter. This atypical NifA-binding site may represent a region interacting
      with two NifA dimers.

PMID- 7585363
TI  - Mother's milk for preterm infants.

PMID- 7585365
TI  - Private health care services.

PMID- 7585366
TI  - Blood lead levels in children: poor methods or good news?

PMID- 7585367
TI  - Blood lead levels in children: poor methods or good news?

PMID- 7585369
TI  - Medical education and society.
AB  - As health care changes under the pressures of restraint and constraint our vision
      of the future of medical education should be based on the medical school's
      responsibility to the community. The medical school is "an academy in the
      community": as an academy, it fosters the highest standards in education and
      research; as an institution in the community, it seeks to improve public health
      and alleviate suffering. The author argues that to better achieve these goals
      medical schools need to become more responsible and responsive to the population
      they serve. Medical schools have been slow to accept fully the social contract by
      which, in return for their service to society, they enjoy special rights and
      benefits. This contract requires that medical educators listen to the public,
      talk honestly and constructively with government representatives and assess the
      needs and expectations of the community.

PMID- 7585372
TI  - Surgical care in rural Canada: training and planning for the future.
AB  - The survey results reported by Chiasson and Roy in this issue (see pages 1447 to
      1452) document a growing problem with the provision of surgical services in rural
      western Canada. Recognizing the need to improve access to surgical services in
      rural communities, the College of Family Physicians of Canada and the Royal
      College of Physicians and Surgeons of Canada have proposed guidelines for
      training family physicians in resuscitative and surgical techniques as well as in
      the safe transfer of seriously ill patients to specialized facilities. It is
      hoped that these guidelines will provide the basis of a national policy for
      general-practice training that will improve the standard of surgical care in
      rural communities.

PMID- 7585370
TI  - Recent trends in the use of inhaled beta 2-adrenergic agonists and inhaled
      corticosteroids in Saskatchewan.
AB  - OBJECTIVE: To examine recent trends in the use of inhaled beta 2-adrenergic
      agonists and inhaled corticosteroids for the treatment of asthma among
      Saskatchewan residents and to determine whether these trends are in keeping with
      widely publicized guidelines recommending a reduction in the use of agents to
      treat symptoms (i.e., inhaled beta 2-adrenergic agonists) and increased use of
      prophylactic agents (i.e., inhaled corticosteroids). DESIGN: Descriptive
      pharmacoepidemiologic study conducted with the use of data from the computerized
      database of the Saskatchewan Prescription Drug Plan. SETTING: Saskatchewan.
      PATIENTS: Saskatchewan residents 5 to 54 years of age who received one or more
      outpatient prescriptions for drugs to treat asthma (inhaled drugs, ingested beta
      2-adrenergic agonists and ingested methylxanthines) from 1989 to 1993. OUTCOME
      MEASURES: Epidemiologic trends, calculated for each year: number of prescriptions
      per 1,000 persons; number of patients who received prescriptions for inhaled
      corticosteroids, inhaled beta 2-adrenergic agonists and any type of drug to treat
      asthma; mean number of such prescriptions per patient; and weighted mean amount
      of salbutamol, fenoterol and beclomethasone dispensed per patient. RESULTS: There
      has been an increase in the proportion of the population receiving prescriptions
      for drugs to treat asthma. The number of patients receiving these drugs per 1,000
      people rose during the study period from 33.38 to 46.59 for any drug to treat
      asthma, from 24.70 to 33.77 for inhaled beta 2-adrenergic agonists and from 6.1
      to 19.9 for inhaled corticosteroids. The mean number of prescriptions per patient
      decreased steadily for all drugs to treat asthma (from 5.34 in 1989 to 3.88 in
      1993), for inhaled beta 2-adrenergic agonists (from 4.35 to 3.09) and for inhaled
      corticosteroids (from 2.98 to 2.25). The weighted mean amount of inhaled
      salbutamol dispensed per patient per year decreased by 40%, from 178.08 mg in
      1989 to 109.14 mg in 1993. The weighted amount of fenoterol dispensed per patient
      per year declined even more, by 58%, from 387.91 mg in 1989 to 164.00 mg in 1993.
      Conversely, the weighted amount of inhaled beclomethasone dispensed per patient
      per year increased by 35% from 46.95 mg in 1989 to 63.50 mg in 1992, then dropped
      to 56.17 mg per year in 1993. CONCLUSION: These data demonstrate a substantial
      change in Saskatchewan in the prescribing of drugs to treat asthma; they suggest
      that many physicians responded to current guidelines advocating increased
      attention to prevention of airway inflammation in the treatment of asthma.

PMID- 7585373
TI  - Meeting the challenge: providing anesthesia services in rural hospitals.
AB  - Although the volume and intensity of surgery done in rural hospitals are not
      sufficient to support a fully trained staff anesthetist, it is not practicable
      for all surgical, anesthesia and obstetric services to be provided by specialists
      in referral centres. As the study reported by Chiasson and Roy in this issue
      shows (see pages 1447 to 1452), general practitioners (GPs) with limited
      additional training in anesthesia already play an important role in the provision
      of these services in rural areas. To ensure that there is a continued supply of
      physicians prepared to meet the needs of small communities, funding and
      opportunities for supplemental training in surgery, anesthesia and obstetrics
      must be made available to GPs.

PMID- 7585368
TI  - No magic bullets: a systematic review of 102 trials of interventions to improve
      professional practice.
AB  - OBJECTIVE: To determine the effectiveness of different types of interventions in
      improving health professional performance and health outcomes. DATA SOURCES:
      MEDLINE, SCISEARCH, CINAHL and the Research and Development Resource Base in CME
      were searched for trials of educational interventions in the health care
      professions published between 1970 and 1993 inclusive. STUDY SELECTION: Studies
      were selected if they provided objective measurements of health professional
      performance or health outcomes and employed random or quasi-random allocation
      methods in their study designs to assign individual subjects or groups.
      Interventions included such activities as conferences, outreach visits, the use
      of local opinion leaders, audit and feedback, and reminder systems. DATA
      EXTRACTION: Details extracted from the studies included the study design; the
      unit of allocation (e.g., patient, provider, practice, hospital); the
      characteristics of the targeted health care professionals, educational
      interventions and patients (when appropriate); and the main outcome measure. DATA
      SYNTHESIS: The inclusion criteria were met by 102 trials. Areas of behaviour
      change included general patient management, preventive services, prescribing
      practices, treatment of specific conditions such as hypertension or diabetes, and
      diagnostic service or hospital utilization. Dissemination-only strategies, such
      as conferences or the mailing of unsolicited materials, demonstrated little or no
      changes in health professional behaviour or health outcome when used alone. More
      complex interventions, such as the use of outreach visits or local opinion
      leaders, ranged from ineffective to highly effective but were most often
      moderately effective (resulting in reductions of 20% to 50% in the incidence of
      inappropriate performance). CONCLUSION: There are no "magic bullets" for
      improving the quality of health care, but there are a wide range of interventions
      available that, if used appropriately, could lead to important improvements in
      professional practice and patient outcomes.

PMID- 7585371
TI  - Role of the general practitioner in the delivery of surgical and anesthesia
      services in rural western Canada.
AB  - OBJECTIVE: To determine the present role of general practitioners (GPs) in the
      delivery of surgical and anesthesia services in rural western Canada. DESIGN:
      Survey by mailed questionnaire in November 1993, with telephone follow-up of
      nonresponders. SETTING: Rural British Columbia, Alberta, the Yukon Territory and
      the Northwest Territories. PARTICIPANTS: Administrators of 148 rural hospitals;
      of the 121 who completed it 101 represented hospitals that met the inclusion
      criteria (fewer than 51 beds and serving a population of 15,000 or less). OUTCOME
      MEASURES: Hospital characteristics, type of practitioners providing surgical and
      anesthesia services, length and location of GPs', surgical and anesthesia
      training, types of surgical procedures performed by GPs and opinions of
      administrators regarding the delivery of surgical services in their community.
      RESULTS: Surgical services were provided by 56 (55%) of the 101 hospitals; at 45
      (80%) they were provided by GPs, and at 33 (59%) they were provided by GPs with
      limited additional surgical training. Fifteen (27%) of the 56 hospitals were said
      to rely solely on GPs with limited surgical training for surgical services. At 45
      (80%) of the 56 hospitals anesthesia services were provided by GPs, all of whom
      had limited additional training in anesthesia; 36 (64%) were said to rely solely
      on GPs for anesthesia services. Just over three quarters (76% [74/98]) of the
      administrators felt that their community's surgical needs were well met.
      CONCLUSION: GPs with limited specialty training continue to play a role in
      providing surgical and anesthesia services in rural western Canada. This has
      implications for postgraduate training programs in Canada.

PMID- 7585375
TI  - Improvement of early renal bone disease with alfacalcidol therapy.

PMID- 7585377
TI  - Physical activity and hypertension.

PMID- 7585376
TI  - Withdrawal of corticosteroid therapy after acute asthma attacks.

PMID- 7585378
TI  - Number of needlestick injuries still a concern.

PMID- 7585374
TI  - Programmed cell death and the gene behind spinal muscular atrophy.
AB  - A gene involved in the development of spinal muscular atrophy (SMA) has been
      found on human chromosome 5 after a 4-year search. Named the neuronal apoptosis
      inhibitor protein (NAIP) gene, it is believed to inhibit the normal process of
      apoptosis--the disintegration of single cells that results from programmed cell
      death--in motor neurons. The researchers who found the NAIP gene also discovered
      that healthy people carry one complete copy of the gene along with many other
      partial copies. Many children with SMA have the partial copies but not the
      complete gene. This discovery facilitates the accurate genetic diagnosis of SMA.
      But gene therapy for SMA will not be possible until researchers find a suitable
      vector to stably introduce activated and intact copies of the gene into the motor
      neurons of children with SMA in time to stop motor neuron loss.

PMID- 7585380
TI  - Crucible of fire: the Boer War and the birth of the Canadian Army Medical Corps.
AB  - Although Canada's military physicians didn't come to prominence until WW I and WW
      II, the Canadian Army Medical Corps (CAMC), the forerunner of the Royal Canadian
      Army Medical Corps and the current Canadian Forces Medical Service, actually had
      its origins in the Boer War. During that turn-of-the-century conflict, field
      hospitals accompanied Canadian troops to South Africa. Ian McCulloch discusses
      that early type of medical service and the steps that led to the creation of the
      CAMC.

PMID- 7585381
TI  - Vancouver conference hailed as latest step in "revolution for children".
AB  - Physicians who organized a major conference on children's health in Vancouver
      this summer say it provided further evidence of the growing strength of a
      "revolution for children." The conference, which attracted 4000 delegates,
      followed up on earlier meetings held to improve the health care available to
      children around the world.

PMID- 7585382
TI  - History and evolution of the role of the medical director.
AB  - Federal regulations that were published in 1974 required a physician to be
      employed full or part time as the medical directory by a skilled nursing
      facilities. Negotiation was needed in each facility to reconcile the traditional
      role of the physician who care for individual patients with the new role of the
      physician who would be involved in decisions regarding the care of groups of
      residents. Professional and provider organizations attempted to define the new
      role, which developed through experience, networking, and educational
      opportunities. A consensus conference held in January 1988 identified the
      functions and tasks associated with medical direction, and, subsequently,
      educational opportunities focusing on the competencies associated with performing
      these tasks and functions were developed. This article traces the history and
      evolution of the formalization of the medical director's role.

PMID- 7585379
TI  - WHO launches school health plan.

PMID- 7585384
TI  - The medical director in the multi-level long-term care facility.
AB  - This article describes the medical director's role in a multi-level long-term
      care facility, the continuing care retirement facility (CCRC). The history of
      CCRCs, different types, services available, and demographics of residents are
      discussed. Special attention is given to the role that the medical director plays
      in providing primary care services for the highest functioning of residents at a
      CCRC.

PMID- 7585383
TI  - Current role of the medical director in community-based nursing facilities.
AB  - The majority of community-based nursing facilities in the United States have part
      time medical directors whose basic training is either in primary care, internal
      medicine, or family practice. Some medical directors have a Certificate of Added
      Qualification in Geriatric Medicine. Very few have received formal training in
      medical direction in long-term care. This article presents information on the
      demographics of community medical staffs and medical directors, administrative
      and medical staff relationships, committee responsibilities, policies and
      procedures, teaching and research, community activities, and resources of value
      that should enhance the ability of part-time medical directors to perform more
      effectively and increase the knowledge of other health professionals about the
      complex role of the medical director in community-based nursing facilities.

PMID- 7585385
TI  - The medical director in hospital-based transitional care units.
AB  - This article begins with a brief overview of what subacute care is and why it is
      growing exponentially. It then discusses the characteristics of patients
      appropriate for treatment in a transitional care unit (TCU) and the evolving role
      of physicians in their care. The process of care in a typical hospital-based TCU
      from admission to discharge is discussed with an emphasis on documentation and an
      interdisciplinary approach. The role of the medical director is emphasized. The
      article closes with strategies the authors feel are useful for improving care in
      hospital-based TCUs.

PMID- 7585387
TI  - The corporate medical director.
AB  - Long-term care is in a period of significant transition driven partially by more
      knowledgeable and demanding consumers, a national focus on controlling health
      care costs, and by the rising acuity level of today's nursing facility patients.
      It is the rising patient acuity level and the increasing array of healthcare
      services they require that is creating a demand for more physician involvement
      and supervision. Similar to the acute care industry, there are now many large
      long-term care provider corporations recognizing the need for physician
      involvement at the senior-management level. This article reviews the
      justification for, the attributes, and the responsibilities of the long-term care
      corporate medical director.

PMID- 7585386
TI  - The medical director in non-institutional long-term care programs.
AB  - Non-institutional long-term care is a broad, poorly defined, rapidly developing
      field. The need for it, the technologic ability to provide it, and the amount of
      money spent on it are all growing. Reconciling the public's reluctance to support
      social programs with the inevitable overlap of social and medical needs in the
      care of the frail elderly presents a serious challenge in formulating policy.
      Medical directors of programs in non-institutional long-term care will have to
      face governmental constraints and will be responsible for developing and
      implementing new policy in the future.

PMID- 7585390
TI  - Policy and procedure development and implementation.
AB  - A basic medical director function is to help draft and implement policies and
      procedures. Physicians should not underestimate the knowledge and skills involved
      in doing it well. Instead of viewing this role as merely unpleasant paper work,
      they should look beneath the surface for the much broader implications. Effective
      medical directors must be astute problem solvers and and analysts of attitudes,
      systems, and processes. The vital role of effective processes in helping apply
      knowledge effectively and improve outcomes deserves much greater recognition and
      study.

PMID- 7585388
TI  - Omnibus Budget Reconciliation Act of 1987 and its implications for the medical
      director.
AB  - The nursing home reform amendments passed by Congress in 1987 (known as OBRA 87)
      have several sections that are relevant to medical practice and medical direction
      in the nursing home. The regulations and interpretive guides specify the medical
      director's role, physician services, resident assessments, resident rights, and
      restrictions on the use of chemical and physical restraints. This article
      provides the nursing home attending physician and medical director with basic
      information to help bring medical services into regulatory compliance.

PMID- 7585391
TI  - Infection control in long-term care.
AB  - Elderly residents of long-term care facilities are especially vulnerable to
      certain infectious diseases such as pneumonia, urinary tract infection, and skin
      or soft tissue infections. As part of quality of care, the detection, control,
      and prevention of infections in long-term care facilities through an organized
      infection control program is a requirement of federal, state, and professional
      regulatory agencies. Implementation of the major components of an infection
      control program requires a cooperative interdisciplinary effort among the
      facility administration, medical director, infection control committee, infection
      control practitioner, staff, and local health department.

PMID- 7585389
TI  - Total quality management and the medical director.
AB  - Physicians practicing in nursing homes can best influence the quality of care by
      managing the processes through which treatment orders are requested by nursing
      home staff and then implemented. This article describes how total quality
      management principles can be used to effectively manage these treatment order
      processes.

PMID- 7585392
TI  - The acute and long-term care interface. Integrating the continuum.
AB  - Acute and long-term care traditionally have been distinctly different health care
      services, separated by reimbursement mechanisms, types and numbers of providers,
      and overall approach to the management of chronic illness. Considerable effort
      has been made of late, primarily due to financial incentives, to integrate these
      two levels of care into a "seamless" continuum. Barriers to such an integration
      process must first be identified. Physician and other health care providers will
      need to develop the tools and resources necessary to manage frail, chronically
      ill patients in settings other than the traditional acute care hospital, as well
      as to develop information systems that allow communication to flow easily between
      all levels of care. As subacute or transitional care becomes a central piece of a
      health care delivery system, those tools become critical to the provision of
      quality, integrated care.

PMID- 7585393
TI  - Academics and the nursing home.
AB  - Several characteristics of the nursing home justify its new found status as an
      academic site, including a heterogenous patient population, a rich and varied
      milieu for teaching, opportunities for faculty development, and more importantly,
      the nursing home's new found position in the health care continuum. Mandates from
      a number of professional and accrediting bodies pertaining to primary care
      training experiences further highlight the nursing home's role in medical
      education. In addition to education, research in the nursing home has become
      increasingly recognized and valued. The incorporation of nursing facilities into
      the academic mainstream will impact positively not only in patient care and age
      related clinical investigation but also on the breadth and quality of training
      for the primary care physician of the future.

PMID- 7585394
TI  - Long-term care reimbursement issues.
AB  - There have been dramatic changes in long-term care funding recently. Considered
      only an insignificant part of the continuum of care system just a few years ago,
      this level of care is now looked to as a wellspring for desperately needed health
      care cost reductions. Government, insurance companies, intermediaries, large
      providers, and consumer and physician groups are actively focused on the
      development and expansion of alternative care provision sites; sub-acute care;
      hospice; home health care; social, medical, and rehabilitative day care; assisted
      living and adult congregate care facilities; risk or capitation contracting;
      expanded health maintenance organizations; alternative care providers; and
      alternative care approaches. In addition, the improvement in reimbursement is
      reviewed and is one aspect in ensuring that the economics are right for those
      needed services to continue to be provided.

PMID- 7585395
TI  - The future of long-term care and the role of the medical director.
AB  - Anticipating the needs of aging baby boomers and responding to market demands for
      consumer choice and low-cost care, long-term care providers are changing the way
      they do business. As part of that change, they are offering new and, in some
      cases, more complex services at both the high and low end of the spectrum. At the
      high acuity end, long-term care providers are delivering hospital-like subacute
      care to increasing numbers of patients at roughly half the costs of providing the
      same care in hospitals. At the low acuity end, providers are offering new
      assisted living services, as well as a full range of community-based long-term
      care. At the same time, traditional nursing facilities continue to meet the needs
      of chronically ill elderly and people of all ages needing rehabilitative care.
      These changes point to a shifting role for physicians (and especially medical
      directors) in the long-term care setting.

PMID- 7585396
TI  - Child psychiatric epidemiology: current status and future prospects.
AB  - OBJECTIVE: The purpose of this paper is to present selected findings from child
      psychiatric epidemiology in areas of prevalence and correlates, and discuss
      issues in interpreting these data and their relevance. METHOD: Selected
      references were used. RESULTS: Prevalence rates of 1 or more child psychiatric
      disorders in nonclinical community samples of children and adolescents vary
      between 17.6% and 22%. Issues in interpreting these data include: the boundary
      between normal and abnormal, boundary between disorders, disagreement among
      informants, and problems with instrumentation. Knowledge about the correlates of
      child psychiatric disorders is quite extensive, but information on causal factors
      is relatively sparse. CONCLUSIONS: Findings in child psychiatric epidemiology are
      relevant to clinicians, and future emphasis in the field will be on prospective
      studies with multiple waves of data from different domains including the child,
      the family, the school, and the wider community.

PMID- 7585398
TI  - Firesetting during the preschool period: assessment and intervention issues.
AB  - OBJECTIVE: To describe a methodology of assessing preschoolers involved in
      firesetting incidents, and outline the psychiatric implications of firesetting
      incidents in young children. METHOD: To outline The Arson Prevention Program for
      Children and present case vignettes. RESULTS: The heightened risk of burn injury
      or fatality in fires caused by young children is highlighted and practical
      suggestions for facilitating the immediate safety of the child and family are
      presented. CONCLUSION: Despite the popular notion that fire interest and play is
      relatively benign in young children, the cases show that, as with older children,
      firesetting in preschoolers can be associated with serious child and/or family
      psychopathology.

PMID- 7585399
TI  - Socio-cultural determinants of psychiatric symptomatology in James Bay Cree
      children and adolescents.
AB  - OBJECTIVE: To examine the type of psychiatric disorders found in 100 Cree
      children living in a Native community in northern Quebec. METHOD: Standardized
      semi-structured interviews were given to all children and their caregivers,
      collecting 24 items of information. RESULTS: 51% of the children did not qualify
      for a DSM-III-R diagnosis but their frequently severe behavioural symptoms could
      be categorized by using 5 types of socio-cultural disturbances. There were also
      significant correlations between parental educational level, including length of
      time spent away from home, and the number of stress factors the children had been
      exposed to. CONCLUSION: There is a need to develop a diagnostic classification
      for child psychiatric disorders for aboriginal children.

PMID- 7585397
TI  - Current research findings on childhood autism.
AB  - OBJECTIVE: To review the main areas of current research findings regarding the
      core deficits in autism and the implications of these findings for the practicing
      clinician. METHOD: Behavioural, cognitive, emotional and neurophysiological
      aspects are covered with an emphasis on the importance of methodology. RESULTS:
      The implication of these findings for the treatment of autism is discussed.
      CONCLUSION: Autism can teach us how we learn about emotions and the possibility
      of sensitive periods of development.

PMID- 7585400
TI  - Conduct disorder and substance use disorder: comorbidity in a clinical sample of
      preadolescents and adolescents.
AB  - OBJECTIVE: To examine the rate of comorbidity between conduct disorder and
      substance use disorder in a clinical sample using the Diagnostic Interview for
      Children and Adolescents--Revised. METHOD: Examined the pattern of conduct
      disorder symptoms, including type, number, and severity, in conduct-disordered
      youth diagnosed with, and without a comorbid substance use disorder. RESULTS: The
      examination revealed no significant differences in the incidence of comorbidity
      between younger (aged 10 to 13) and older (above age 13) youth. Among youth who
      met criteria for conduct disorder, 52% also met criteria for a substance use
      disorder. Odds ratios indicated that the probability of comorbidity of conduct
      and substance use disorders was higher in the younger group. CONCLUSION:
      Substance abuse and dependence tend to develop rapidly following first use,
      suggesting that a slim window of opportunity exists to prevent substance
      disorders once drug use has begun.

PMID- 7585401
TI  - Short-term efficacy of interventions by a youth crisis team.
AB  - OBJECTIVE: To determine the impact of an outpatient psychiatric Emergency Room
      Follow-up Team (ERFUT) on the hospitalization rate of youth in crisis (mostly
      suicidal adolescents). METHOD: The rate of psychiatric admissions of youth to a
      general pediatric hospital during a year prior to the ERFUT creation was compared
      to that same rate after the team's creation. The proportion of patients returning
      to the Emergency Room (ER) 2 or more times was also compared for those same
      years. Deaths were identified at 3-year follow-up for the experimental group.
      RESULTS: A 16% reduction in the hospitalization rate followed the team's
      creation, without an increase in the proportion of patients returning to the ER.
      Also, none of the experimental group subjects had died at 3-year follow-up.
      CONCLUSION: There is a subpopulation of previously hospitalized suicidal
      adolescents who can be effectively cared for as outpatients when treated rapidly
      and intensively.

PMID- 7585402
TI  - Tricyclic medication in children and the QT interval: case report and discussion.
AB  - OBJECTIVE: To identify the necessity for close monitoring of the QT interval in
      children and adolescents treated with tricyclics. METHOD: Guidelines for
      permissible ECG changes are reviewed and a case report of a 12-year-old girl with
      idiopathic long QT syndrome, no history of cardiac disorder, a questionable
      family history, and normal physical examination and baseline ECG is presented.
      RESULTS: Marked increase in QT corrected for heart rate (QTc) occurred on low
      dose tricyclic. Possible factors in deaths on desipramine are reviewed.
      CONCLUSION: It is recommended that children and adolescents on tricyclics receive
      an ECG at baseline and after each dose increase. Recommendations are made
      regarding ECG parameters and indications for cardiac consultation.

PMID- 7585405
TI  - Training residents for rural child psychiatry: defining the objectives.
AB  - OBJECTIVE: To discuss the contribution of consultative skills to the practice of
      child psychiatry and to develop curriculum which enhances the ability of
      residents to participate in community-based care. METHOD: The development of a
      training site for residents and fourth year medical students in a weekly half-day
      travelling child psychiatry clinic to a rural children's aid society is
      described. A method of designing educational objectives for community-based
      training is reviewed and expanded to provide a template for constructing a
      comprehensive curriculum. RESULTS: The educational objectives specific to the
      rural training site chosen are provided and their contribution as a subset of the
      curriculum is defined. CONCLUSION: The authors suggest that a more fulsome
      discussion of curriculum design and content in the Canadian literature will aid
      in the development of emerging practice patterns in child psychiatry.

PMID- 7585407
TI  - Psychiatric abuse in Cuba.

PMID- 7585403
TI  - The acute management of aggressive behaviour in hospitalized children and
      adolescents.
AB  - OBJECTIVE: To examine how health care professionals attempt to manage acutely
      aggressive behaviours exhibited by children and adolescents in various hospital
      settings. METHOD: A review of the literature examining management techniques on
      child psychiatric and pediatric wards is presented. Techniques reviewed include
      pharmacotherapy, psychotherapy, seclusion, restraint and the use of pro re nata
      (prn) medications. RESULTS: Effects of various management techniques are
      presented, where available. CONCLUSION: There is little evidence for the
      effectiveness of most presently used acute management techniques in containing
      aggressive child behaviours over the long term. Suggestions for improved
      evaluation of management techniques are made.

PMID- 7585404
TI  - Mendacious moms or devious dads? Some perplexing issues in child custody/sexual
      abuse allegation disputes.
AB  - OBJECTIVE: To explore relevant literature about sexual abuse allegations arising
      in child custody disputes. METHOD: A literature review of false allegations is
      given and the contribution of gender bias to this issue is discussed. The role a
      child psychiatrist may play in such cases is outlined. RESULTS: Contrary to much
      popular and professional opinion, sexual abuse allegations are found in only 2%
      of child custody disputes, and, of these, 8% to 16.5% are false. While false
      allegations arise for a variety of reasons, the word "false" can imply both
      erroneous and deceitful activities. This ambiguity, along with gender bias, may
      lead to disbelief of, and blame towards, parents who report sexual abuse in the
      context of a dispute about custody or access. CONCLUSION: The child psychiatrist
      who testifies in such custody disputes should have caution, humility, and an open
      mind both in the courtroom and in dealing with other professionals working in
      this area.

PMID- 7585408
TI  - Re: Immigrant and refugee children in Canada.

PMID- 7585406
TI  - The function of the multidisciplinary team in child psychiatry--clinical and
      educational aspects.
AB  - OBJECTIVE: To present experiences with teams in a university hospital and various
      community settings that promote the learning of collaboration among different
      professionals. METHOD: Research in developmental psychopathology has increasingly
      linked childhood vulnerabilities and risk factors to adolescent and adult
      disorders. In this context the multidisciplinary teams can be seen as the
      expression of the expanding knowledge and expertise of the medical and allied
      health professionals, which can be directed toward promotion of health as well as
      prevention and cure of illness. RESULTS: Collaboration reflects the application
      of biopsychosocial principles to consultation and research both in the community
      and in hospital, and the general trend in medicine to move from solo to team
      practice. CONCLUSION: Psychiatrists have the obligation to promote, develop and
      maintain the psychosocial and personal dimension in the teaching and practice of
      medicine.

PMID- 7585409
TI  - Re: A treatment for impulse control disorders.

PMID- 7585410
TI  - The loss of the therapeutic effect of antidepressant medication.

PMID- 7585411
TI  - Hair loss associated with fluoxetine but not with citalopram.

PMID- 7585412
TI  - Personality disorder in alcohol dependents.

PMID- 7585413
TI  - Re: Auto-erotic asphyxial death.

PMID- 7585414
TI  - Evaluation of methods for the euthanasia of cattle in a foreign animal disease
      outbreak.

PMID- 7585415
TI  - Enthusiasm is contagious.

PMID- 7585417
TI  - Effects of various vaccination protocols on passive and active immunity to
      Pasteurella haemolytica and Haemophilus somnus in beef calves.
AB  - Two field trials were conducted in a beef cow herd in Saskatchewan to determine
      the effectiveness of a combined Pasteurella haemolytica and Haemophilus somnus
      vaccine in increasing passively and actively acquired antibodies in beef calves.
      Vaccination of dams at 4 and/or 7 weeks prepartum was associated with increased
      antibody titers to P. haemolytica and H. somnus in their serum (P < 0.05),
      colostrum(P < 0.05), and serum of their calves at 3 days and 1 month of age (P <
      0.05). There was no significant(P > 0.05) difference in antibody titers in the
      colostrum and serum of calves from single or double vaccinated dams. Calves
      vaccinated at 1 and 2 months of age in the face of maternal antibodies toP.
      haemolytica and H. somnus had significantly(P < 0.05) higher antibodies to P.
      haemolytica and H. somnus at 4 and 6 months of age than did unvaccinated calves.
      Calves vaccinated at 3 and 4 months of age in the face of low levels of
      preexisting antibodies had significantly (P < 0.05) higher antibodies toP.
      haemolytica at 5 months of age and to H. somnus at 5 and 6 months of age than did
      unvaccinated calves. Calves vaccinated once at 4 months of age had
      significantly(P < 0.05) higher antibody titers toP. haemolytica and H. somnus at
      4.5 months of age than did unvaccinated calves, but this difference was not
      apparent at 6 months of age. These results suggest that vaccination of beef cows
      with a combined Pasteurella haemolytica and Haemophilus somnus vaccine once at 4
      weeks prepartum will significantly (P < 0.05) increase passive antibody titers
      toP. haemolytica and H. somnus in their calves. Double vaccination of calves with
      preexisting maternal antibodies at 1 and 2 months of age will increase antibody
      titers to P. haemolytica and H. somnus until 6 months of age. Vaccination of beef
      calves with low levels of preexisting antibody at 3 and 4 months of age will
      increase antibody titers to H. somnus until 6 months of age and to P. haemolytica
      until 5 months of age.However, the level of antibodies achieved by vaccination
      may depend on the calves being studied, the level of preexisting antibodies, and
      the efficiency of passive transfer.

PMID- 7585416
TI  - An ethicist's commentary on the case of the recent graduate who is offended by
      conversations between employers.

PMID- 7585418
TI  - Cecal impaction in a cow.

PMID- 7585419
TI  - Pseudocyst of the testis of a prepubertal horse.

PMID- 7585421
TI  - Craniomandibular osteopathy in a Shetland sheepdog.

PMID- 7585423
TI  - Critical thinking: radiographic misdiagnoses in horses.

PMID- 7585424
TI  - Haemobartonella canis infection following splenectomy and transfusion.

PMID- 7585426
TI  - Yew poisoning in sheep.

PMID- 7585420
TI  - Pyriform bovine spermatozoa and fertilization potential.

PMID- 7585428
TI  - Further thoughts on the use of bovine somatotropin.

PMID- 7585425
TI  - Anaranthus retroflexus (redroot pigweed) poisoning in lambs.

PMID- 7585422
TI  - Diffuse abdominal epithelioid mesothelioma in a cow.

PMID- 7585427
TI  - Potomac horse fever in eastern Ontario.

PMID- 7585430
TI  - An ethicist's commentary on the case of a client who refuses euthanasia for a
      sick cat.
AB  - An 8-year-old, neutered, male, domestic shorthaired cat is admitted to your
      clinic with a complaint of lethargy and anorexia. The cat was last examined 2
      months previously with a urinary tract infection and severe cellulitis at the
      site of a ventral abdominal urethrostomy. The urethrostomy was performed several
      years ago at another clinic. Euthanasia was recommended during your first
      examination, but the owner insisted on treatment. The cat improved after
      receiving fluids and systemic and topical antibiotics, but its condition suddenly
      deteriorated 2 days ago. Physical examination reveals severe dehydration,
      bradycardia, hypothermia, and an infected and fly-blown urethrostomy opening.
      Euthanasia is again recommended. The owner refuses and leaves the clinic,
      apparently intending to seek a second opinion.

PMID- 7585431
TI  - Premedication of fragile dogs and cats.

PMID- 7585429
TI  - Treatment of canine sarcoptic mange using milbemycin oxime: a correction.

PMID- 7585432
TI  - Canine streptococcal toxic shock syndrome in Ontario: An emerging disease?

PMID- 7585435
TI  - Discoid lupus erythematosus.

PMID- 7585433
TI  - "No-mucus skin disease" of farmed Atlantic salmon (Salmo salar) fingerlings in a
      freshwater lens in British Columbia.

PMID- 7585434
TI  - Ocular and orbital porcupine quills in the dog: a review and case series.
AB  - A retrospective evaluation of 5 cases of orbital or intraocular porcupine quills
      in the dog and a literature review from MEDLINE (1983-1995) is presented. This
      paper reviews the diagnosis, therapy, and visual prognosis of ocular and orbital
      quills in the dog. Distinguishing penetration and perforation of the eye and
      intraocular structures is paramount in establishing a visual prognosis and
      appropriate therapy. Perforation of the cornea or sclera, lens, or the uvea and
      retina necessitates prompt specialized surgical therapy to save vision. The
      diagnosis of orbital quills can be readily confirmed with ultrasonography. The
      characteristic sonographic appearance of a double-banded, linear, hyperechoic
      object allows accurate localization of the quill, which aids surgical removal.

PMID- 7585436
TI  - The pathogenesis and diagnosis of canine hip dysplasia: a review.
AB  - Hip dysplasia is a common developmental problem affecting the canine population.
      Despite extensive research into the condition, many questions remain unanswered
      and numerous misconceptions are present among the general public. The purpose of
      this paper is to review the current knowledge on the development of hip
      dysplasia, factors modifying its development, and current diagnostic techniques.A
      computerized literature search was conducted for the period of January 1983 to
      April 1985 using the MEDLINE and CAB databases, and the keywords hip dysplasia,
      hip, dog, and canine. Other articles,wherever possible original research
      articles, published before 1983 were also reviewed. Animals affected by hip
      dysplasia are born with normal hips, but quickly develop subluxation of the
      femoral head. Degenerative joint disease follows. Hip dysplasia is a complex,
      inherited, polygenic trait. Selective breeding of only normal dogs with normal
      littermates, parents, and grandparents is there commended method of reducing the
      incidence in the general population.Gene expression in affected individuals may
      be modified by a number of environmental factors. These factors do not cause hip
      dysplasia, but they alter manifestations of the trait and its severity. Nutrition
      is a major environmental factor. Excess energy consumption increases the
      frequency and severity of hip dysplasia in genetically predisposed dogs. Food
      intake should be regulated to maintain a slender figure with the ribs and dorsal
      vertebral spines easily palpable, but not visible. Excess dietary calcium and
      vitamin D contribute to hip dysplasia in genetically predisposed individuals and
      should be avoided. High dose vitamin C supplementation ingrowing puppies does not
      prevent hip dysplasia, and this practice should be discontinued. Animals must be
      2 years old before they can be certified as normal, but the disease may be
      diagnosed earlier. Earlier diagnosis of the condition would be very useful for
      the selection of breeding stock, but palpation techniques and the standard
      extended view radiographs have unacceptably high rates of error in young puppies.
      Stress radiography techniques may improve the accuracy of early diagnosis in the
      future.

PMID- 7585437
TI  - Treatment of canine hip dysplasia: a review.
AB  - This article discusses the treatment approaches and recommendations for canine
      hip dysplasia. A search of the literature database MEDLINE (1969-1994) was
      conducted and relevant journal articles regarding the medical and surgical
      treatment of hip dysplasia were selected and reviewed. Dysplastic dogs can be
      divided, for treatment purposes, into those with no or minimal osteoarthrosis,
      and those with moderate to severe osteoarthrosis. In young animals with joint
      laxity and pain, but with no or minimal radiographic evidence of osteoarthrosis,
      the treatment approach is controversial. Conservative management may be effective
      in the short term, but progressive development of osteoarthrosis occurs and
      clinical signs may manifest at an older age. Options for surgical treatments in
      these young dogs include pectineal myectomy, lengthening of the femoral neck, and
      corrective osteotomies. Corrective osteotomies are advocated to reestablish joint
      congruency and prevent development of osteoarthrosis. In the mature
      osteoarthritic dog, effective conservative management depends on the severity of
      the degenerative joint disease. Proposed surgical treatments for clinically
      debilitating hip dysplasia include biocompatible osteoconductive/shelf
      arthroplasty; femoral head and neck excision arthroplasty, with or without muscle
      sling interposition; and total hip replacement. Although research directly
      comparing the salvage procedures has not been reported, studies suggest that
      total hip replacement is more effective in returning large dogs to full
      functional weight bearing.

PMID- 7585441
TI  - Diagnostic ophthalmology. Amelanotic melanoma in an 8-year-old cat.

PMID- 7585440
TI  - Methemoglobinemia and anemia in a dog with acetaminophen toxicity.

PMID- 7585438
TI  - Injuries suffered by dogs from riding in the back of open pickup trucks: a
      retrospective review of seventy cases.
AB  - Case records of 70 dogs injured while riding in the back of open pickup trucks
      during the period January 1, 1982, to May 1, 1993, were reviewed. Most dogs were
      young (mean age 2.4 y) and of medium to large size (average weight 22.6 kg).
      Sixty-five dogs (93%) were injured during the months of April through October.
      Forty-nine dogs (70%) had single injuries and 21 dogs (30%) sustained multiple
      injuries. Fractures were the most frequent injury incurred, with fractures of the
      femur the most common. Surgical repair was recommended in all but 2 cases.

PMID- 7585439
TI  - Canine Lyme borreliosis in Ontario--a case report.

PMID- 7585442
TI  - Ultrastructural aspects of DRG satellite cell involvement in experimental
      cisplatin neuronopathy.
AB  - Different substances may induce neurological impairment, clinically expressed as
      peripheral neuropathies, due to damage of the neuronal bodies (neuronopathy) of
      sensory or motor neurons. Neuronopathies have generally been studied referring to
      neurons, although other cellular components may also be damaged. Cisplatin (CDDP)
      is known to be neurotoxic to the neurons of the dorsal root ganglia (DRG). The
      scarcity of information as to the possible involvement and role played by dorsal
      root ganglion (DRG) satellite cells in neuronopathies prompted this study using
      the chronic DRG neuronopathy induced by the repeated administration of CDDP in
      rats as a model. Eighteen female Wistar rats were treated according to 3
      different schedules of CDDP administration (6 rats for each group). Six further
      animals were used as controls. At the end of the experiment the L4-L5-L6 dorsal
      root ganglia were examined at the light and electron microscope. Ag-NOR reaction
      was also examined in 4 further CDDP-treated rats and 4 controls. Pathological
      changes in satellite cells of animals treated with CDDP were remarkable in the
      nucleus where heterochromatin clumps were reduced or even completely absent.
      Morphometric analysis of the area occupied by heterochromatin indicated that this
      nuclear component decreased in an exposure-time dependent manner. Frequently,
      nucleolar-like structures became apparent in the nucleus of the rats treated with
      the higher doses of CDDP. Ag-NOR positive regions in the nuclei of treated rats
      were increased with respect to the controls. Cytoplasmic changes in DRG satellite
      cells of CDDP treated rats were limited, being characterized by an increased
      electron-density of the matrix. In treated rats deep invaginations between
      satellite cells and the neuronal surface were evident, leading to the formation
      of vacuoli. The interstitial connective space often showed edematous areas. Our
      observations demonstrate that in chronic cisplatin neuronopathy, DRG satellite
      cells are also involved in the pathological changes induced by drug exposure, and
      that these changes may be interpreted as being mainly reactive.

PMID- 7585445
TI  - Toxic and neurogenic factors in chloroquine myopathy fibre selectivity.
AB  - Biopsies from soleus and extensor digitorum longus (EDL) muscles obtained in rats
      with an experimental chloroquine myopathy were studied ultrastructurally. Two
      different histopathological pictures were observed: type I fibres from soleus
      exhibited a vacuolar myopathy with an almost normal sarcomeric structure; type II
      fibres from EDL did not show vacuoles but changes similar to neurogenic atrophy.
      Our results suggest that chloroquine produces direct toxic effects in type I
      fibres and secondary neurogenic damage in type II fibres.

PMID- 7585444
TI  - Morphological changes induced in HEp-2 cells by Salmonella typhimurium porins.
AB  - The effects of different doses of Salmonella typhimurium porins were investigated
      on human laryngeal epithelial (HEp-2) cells by fluorescence and transmission
      electron microscopy. The changes observed in microfilament organization suggested
      an involvement of cytoskeleton in the cell response. Furthermore, morphologic
      phenomena characterized by ultrastructural membrane modifications also involved
      the nuclear membrane.

PMID- 7585443
TI  - Structural alterations of human immortal astrocytes after inhibition of 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase by lovastatin.
AB  - This investigation was designed to study the specific structural alterations of
      astroglial cells following the inhibition of 3-hydroxy-3-methylglutaryl coenzyme
      A (HMG-CoA) reductase, which is a key enzyme in cholesterol synthesis. In our
      previous investigations, it has been demonstrated that lovastatin, which is a
      specific competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase, effectively inhibited cholesterol synthesis in human primary and
      immortal astrocytes in serum and lipid-free media, and we also showed that the
      effects on both astrocytes of primary cultures and immortal astrocytes (ASCh-7)
      were very similar. In the present study we therefore examined effects of
      lovastatin at a concentration of 100 ng/ml on human immortal astrocytes (ASCh-7)
      using electron microscopic analysis. We have found that lovastatin significantly
      affects human immortal astrocytes, resulting in degenerative ultrastructural
      changes including accumulation of a large number of phagosomes, oedema of the
      cytoplasm and destruction of gliofilaments. The results obtained suggest that the
      human immortal astrocyte cell line (ASCh-7) can be not only very useful for
      screening drugs in pharmacological research but can also provide a useful model
      for examining fine structural alterations of cells following selective
      disturbances of metabolism.

PMID- 7585446
TI  - An ultrastructural and immunocytochemical study of thoracic aortic endothelium in
      aged Sprague-Dawley rats.
AB  - The distribution of various vasoactive agents [nitric oxide synthase (NOS)- type
      I, endothelin-1 (ET-1), arginine-vasopressin (AVP), serotonin (5-HT), histamine
      and substance P (SP)] in the thoracic aortic endothelium of aged Sprague-Dawley
      rats was investigated using electron microscopic immunocytochemical methods. The
      aged thoracic aortic intima was characterized by a large number of leukocytes
      that adhered to the endothelium, an accumulation of a flake-like precipitate and
      clusters of leukocytes and smooth muscle cells (SMC) in the subendothelium. Age
      associated alterations were also seen in the medial and adventitial layers of the
      vascular wall. An extensive vasa-vasorum was present in the adventitia from which
      leukocytes penetrated into perivascular tissue. Some vasa-vasorum showed mast
      cells adhered to perivascular pericytes. Immunocytochemistry showed about 70%
      endothelial cells (EC) with positive immunostaining for the brain isoform NOS
      type I, compared to 10% in adult mature rats. About 10% of cells showed a
      positive immunoreaction for ET-1, which is about the same as for the mature adult
      thoracic aorta (8-9%). Subendothelial macrophages often showed positive
      immunostaining for antibodies against ET-1. The percentage of EC immunopositive
      to AVP, 5-HT, and histamine was 16-18, 15 and 12%, respectively compared to 5-8,
      7-8 and 6% in mature adult rats. A few cells showed an immunopositive reaction
      for SP. In summary, the ageing vessel was characterized by a large number of
      leukocytes adhering to the endothelium and also by the presence of many
      macrophages and SMC in the subendothelial layer. The percentage of EC in rat
      thoracic aorta showing NOS immunostaining increased substantially from 10% in
      mature rats to 70% in aged rats. The percentage of EC immunopositive for AVP, 5
      HT and histamine also increased about twofold compared to mature adult rats,
      while no changes were seen for ET-1.

PMID- 7585447
TI  - Inhibitory effects of vesicles shed by human breast carcinoma cells on lymphocyte
      3H-thymidine incorporation, are neutralised by anti TGF-beta antibodies.
AB  - When membrane vesicles shed in vitro by 8701-BC, a human breast carcinoma cell
      line, are added to peripheral blood lymphocytes, a strong, dose dependent
      inhibition of the lymphocyte capability to incorporate 3H-thymidine is observed.
      Inhibition is evident on both PhA stimulated and non stimulated lymphocytes, it
      is not specie-specific and occurs after three days of culture. Vesicles shed by
      the human breast carcinoma cell line MCF-7 have inhibitory effects similar to
      those observed with 8701-BC vesicles, but vesicles shed by HT-1080, a human
      fibrosarcoma cell line, do not inhibit, but rather stimulate 3H-thymidine
      incorporation by peripheral blood lymphocytes. The inhibitory effect of vesicles
      shed by human breast carcinoma cells is recovered in their acid soluble
      components, and it is completely neutralised by anti TGF-beta 1 antibodies. These
      findings suggest a role for shed vesicles, in the escape of breast carcinoma
      cells from immunological surveillance. The immune suppressing cytokine TGF-beta,
      which is produced by breast carcinoma cells, could be specifically delivered to
      lymphocytes reacting with vesicles, which are HLA positive, tumour-associated
      antigen-rich, membrane structures.

PMID- 7585448
TI  - Extracellular and intracellular rickettsia-like microorganisms in gonads of
      mosquitoes.
AB  - The mosquitoes Culex tigripes, C. decens and C. quinquefasciatus have been
      investigated by electron microscopy. An intracytoplasmic rickettsia-like
      microorganism is present in ovaries and testes of the three species. An
      extracellular form of a rickettsia-like microorganism is described in the testis
      of C. tigripes in which it sometimes appears in great number. The extra- and
      intracellular forms present ultrastructural differences. The possibility they
      represent two different morphotypes of the same microorganism or simply two
      different types is discussed. They both disappear after treatment with
      tetracycline. This is believed to be the first electron microscope description of
      extracellular rickettsia-like cells in mosquitoes.

PMID- 7585450
TI  - Submicroscopic mathematical evaluation of spermatozoa in assisted reproduction.
      I. Intracytoplasmic sperm injection. (Notulae seminologicae 6).
AB  - After a large introduction concerning the influence of sperm quality in the
      success of in vitro fertilization, the debated problem of the importance of the
      sperm quality in intracytoplasmic sperm injection is investigated. The
      spermatozoa are studied by electron microscopy, and the results evaluated by the
      formula of Baccetti et al. (1995). The quality of spermatozoa has been correlated
      with the success of ICSI. The first conclusion has been that ejaculates which
      produced embryos contained higher percentages and overall higher total number of
      'healthy' spermatozoa than those which obtained fertilizations arrested at the
      two pronuclei stage, or showed no fecundation at all. A second conclusion was
      that the quality of sperm organelles is mainly involved in the oocyte activation,
      but after the 2 pronuclei stage, segmentation usually proceeds with few
      influences from sperm quality. The highest involvement of spermatozoa is
      therefore the initiation of oocyte activation. A third conclusion confirmed the
      need of ultrastructural evaluation of sperm cell organization, deeply
      investigating the inner organelles. Moreover, we observed that the head
      organelles are more involved that the tail ones. Three acrosomal characteristics
      are concerned: the shape, the dimensions and the content. All of them are
      significantly better in the oocyte activating than in non activating spermatozoa.
      Also the nuclear shape and the status of the chromatin (frequently strictly
      interdependent) are significantly concerned with the oocyte activation and with
      the embryo segmentation. In the tail, the mitochondrial shape is significantly
      different in activating and not activating spermatozoa, and also in those
      producing embryo segmentation. Moreover, the absence of dynein arms seems to be
      determinant in impeding the oocyte activation.

PMID- 7585449
TI  - Human sperm and spermatogonia express a galactoglycerolipid which interacts with
      gp120.
AB  - Sexual transmission is a major mode of spread of HIV-1 although the mechanisms
      involved remain to be elucidated. The role of spermatozoa as carriers of the HIV
      is supported by recent publications, while the expression of the CD4 on the
      membrane of the sperm has not yet been demonstrated. The data reported in this
      paper show that a glycolipid molecule, most likely the galactosyl-alkyl
      acylglycerol, structurally similar to galactosylceramides, is present on the
      surface membrane of the spermatozoa. Consistent with a structure similar to
      galactosylceramide, the sperm glycolipid is capable of binding the gp120 as
      demonstrated utilizing an improved ELISA assay which favors sensitivity and
      specificity. Immunocytochemistry of testicular tissue shows the presence of this
      glycolipid on the membrane of immature germ cells, preferentially in the
      spermatogonia. These data indicate that human sperm express a glycolipid similar
      in structure to the receptor for HIV described on the CD4- neural and colonic
      epithelial cell lines, and moreover suggest that this glycolipid could also
      function as HIV receptor and possibly be implied in its transmission. The
      demonstration that this molecule is also expressed by the spermatogonia suggests
      its involvement in the interaction of the HIV with spermatogonia, as recently
      reported, and could explain the inhibition of spermatogenesis observed in AIDS
      patients.

PMID- 7585451
TI  - Frequent mutations of Ki-ras codon 12 in N-bis (2-hydroxypropyl)-nitrosamine
      initiated thyroid, kidney and lung tumors in Wistar rats.
AB  - N-Bis (2-hydroxypropyl) nitrosamine (DHPN) is a very potent mutagen and wide
      spectrum carcinogen in rodents. In the present study, we investigated mutational
      activation of the Ki-ras gene in eight thyroid, five kidney (four mesenchymal and
      one transitional cell lesion) and two lung tumors induced with DHPN. Mutations
      were identified using single-strand conformation polymorphism, restriction
      fragment length polymorphism and DNA sequencing analysis. All of the 15 neoplasms
      could be shown to have mutations in codon 12 (GGT-->GAT). These results suggest
      that Ki-ras mutations are frequent events during the development of DHPN-induced
      carcinomas in these organs. In a separate experiment, moreover, we analyzed the
      presence of Ki-ras mutations in various tissues 8 weeks after DHPN treatment. One
      of five thyroid tissues treated with DHPN was found to have the same
      characteristic mutation, suggesting that it may represent an early event during
      carcinogen-induced tumor formation in the thyroid.

PMID- 7585453
TI  - Loss of heterozygosity of APC/MCC gene in differentiated and undifferentiated
      gastric carcinomas in Taiwan.
AB  - Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were
      identified, and also shown to be associated with the development of esophageal
      and lung cancers. To determine if these genes are also involved in the
      development of gastric cancer, 79 primary human gastric cancers were examined for
      loss of heterozygosity of APC or MCC or both. Loss of APC was detected in 20% of
      15 informative differentiated cases, but not in 20 informative undifferentiated
      cases, while loss of MCC occurred in 23.5% of 17 informative undifferentiated
      cases, but not in 19 informative differentiated cases. These data suggest that
      loss of heterozygosity of APC/MCC gene is involved in the development of gastric
      carcinomas, and that distinctly different molecular mechanism(s) may be
      responsible for the development of differentiated and undifferentiated gastric
      carcinomas.

PMID- 7585452
TI  - Histogenesis of adenosquamous bronchogenic carcinoma.
AB  - In our hamster lung cancer model studies, among 463 non-small-cell lung cancers
      (NSCLC), there were 47 adenosquamous neoplasms. In 24 of 27 lesions with
      diameters of less than 3.0 mm, the adenocarcinoma and the squamous cell carcinoma
      components arose as separate, spatially discrete lesions, but these were separate
      in only 7 of 20 lesions with diameters of 30 mm or greater. Co-infiltration of
      the components became more frequent as tumor size increased. The usual
      adenosquamous variety of NSCLC is likely a collision tumor, with each component
      possessing separate biological characteristics. Thus, future prognostically
      directed studies of this variety of NSCLC must recognize that these neoplasms
      have two components, each of which needs to assessed.

PMID- 7585454
TI  - Linear relationship between flux density and tumor co-promoting effect of
      prolonged magnetic field exposure in a breast cancer model.
AB  - Previous epidemiologic studies have suggested that exposure to 50- or 60-Hz
      (power-frequency) magnetic fields in occupational or residential environments may
      increase the risk of certain cancers, including breast cancer. However, in view
      of the methodological problems of epidemiological studies on associations between
      magnetic field exposures and increased incidence of cancers, laboratory studies
      are necessary to determine if 50/60-Hz magnetic fields are cancer promoters or
      can progress cancers. The objective of the present study was to characterize the
      relation, if any, between dose (i.e. flux density) of 50-Hz magnetic field
      exposure and tumor growth in a model of breast cancer in female rats. Mammary
      tumors were induced by the chemical carcinogen 7, 12-dimethylbenz[a]anthracene
      (DMBA). The dosing protocol of DMBA chosen for the magnetic field experiments
      induced mammary tumors in about 50% of sham-exposed control animals within 3
      months after application. Per flux density, a group of 36-99 rats was exposed to
      a magnetic field of 50-Hz for 24 h/day 7 days/week; another group of 36-99 rats
      was sham-exposed under the same environmental conditions as the MF-exposed rats.
      The exposure chambers were identical for MF-exposed and sham-exposed animals.
      DMBA was administered orally at a dose of 5 mg per rat at the first day of
      exposure and at weekly intervals thereafter up to a total dose of 20 g per rat.
      Duration of MF- or sham-exposure was 91 days. At the end of the exposure period,
      the animals were sacrificed for examination of the number of mammary tumors. Four
      flux densities were studied in a total of 666 rats (including sham-exposed
      controls): 0.3-1 muT, 10 muT, 50 muT, and 100 muT. At autopsy, i.e. at the end of
      the 13 weeks period of MF-exposure, incidence of macroscopically visible mammary
      tumors was significantly enhanced in the experiment with 50 muT (25.5% above
      control) and 100 muT (50% above control). No increase in incidence of mammary
      tumors was seen in the experiment with 0.3-1 muT, while a 10% (non-significant)
      increase was determined in the experiment with 10 muT. Linear regression analysis
      of the data from the four experiments indicated a highly significant linear
      relation between flux density and increase in tumor incidence at time of autopsy.
      The correlation coefficient was 0.9944 (P < 0.01). The data demonstrate that long
      term exposure of DMBA-treated female rats increases the growth of mammary tumors
      in a highly dose-related fashion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7585455
TI  - Intracellular ATP is required for actinomycin D-induced apoptotic cell death in
      HeLa cells.
AB  - In the present report, we demonstrate that reduction of cellular ATP content with
      antimycin A blocks actinomycin D-induced apoptotic cell death in HeLa cells.
      Compared to cells (approximately 80%) treated with actinomycin D (1 microgram/ml;
      48 h) alone in glucose-containing medium, a much smaller percentage of cells
      (approximately 20%) treated with actinomycin D in the presence of antimycin A in
      glucose-free medium shows morphological characteristic of apoptosis. ATP-depleted
      cells with or without actinomycin D treatment, on the other hand, die
      necrotically. In cells under actinomycin D short exposure treatment (1
      microgram/ml; 1 h), apoptosis occurs when cellular ATP content is rapidly
      recovered after the removal of antimycin A and resupplementation of glucose
      containing medium. In the incubation of isolated Triton-permeabilized cells with
      ATP ( > 0.5 mM), apoptotic nuclei become abundant 4 h after ATP treatment. These
      results implicate the requirement of ATP for the induction of apoptosis.

PMID- 7585456
TI  - Glyoxalase activities in tumor and non-tumor human urogenital tissues.
AB  - Glyoxalase I and glyoxalase II activities have been measured in human tumor and
      non-tumor samples of 15 kidneys, 15 bladders, 4 testes, 2 adrenals as well as in
      4 samples of prostatic adenomas. In all tissues examined glyoxalase I and
      glyoxalase II activity values varied widely from one patient to another. No
      significant difference in glyoxalase I activity between the tumor and non-tumor
      samples was found. When comparison was made between normal and neoplastic tissues
      of the same patients, glyoxalase I activity was found to be lower in tumor
      tissues of 10 out of 15 kidneys, and 2 out of 8 bladders and 1 out of 3 testes. A
      significant (P < 0.004) decrease of glyoxalase II activity was found only in
      tumor kidney. The possibility of using the present data to predict the relative
      sensitivity of human tumor tissues to glyoxalase-related chemotherapy is
      discussed.

PMID- 7585457
TI  - Influence of various concentrations of taxol on cell survival, micronuclei
      induction, and LDH activity in cultured V79 cells.
AB  - The clastogenic effect of various concentrations of taxol, namely 0, 10, 25, 50,
      100, 250 and 500 nM was evaluated in V79 cells grown in vitro. Treatment of V79
      cells with different concentrations of taxol reduced the survival in a
      concentration dependent manner. However, the frequency of micronuclei increased
      in a concentration dependent manner and the dose response was linear quadratic.
      Similarly, lactate dehydrogenase also increased with the increase in taxol
      concentration. The micronuclei and lactate dehydrogenase showed an inverse
      relationship with the cell survival.

PMID- 7585459
TI  - Effect of rat thyroid proliferative lesion development by intermittent treatment
      with sulfadimethoxine.
AB  - To determine whether production of thyroid proliferative lesions would be
      enhanced by intermittent rather than continuous treatment with a goitrogen, male
      F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2800 mg/kg body
      weight, single s.c. injection) were given water containing 0.1% sulfadimethoxine
      (SM) for 20 weeks (group 1) or 0.1% SM for the first 8 weeks followed by 2 cycles
      consisting of 2 weeks withdrawal and 4 weeks retreatment with 0.1% SM (group 2).
      Control rats (group 3) were untreated for 20 weeks after the DHPN initiation.
      Serum T3 and T4 levels were significantly decreased in groups 1 and 2 compared to
      group 3. Serum thyroid stimulating hormone level was significantly increased in
      all treated groups compared to group 3. The numbers of follicular cell
      hyperplasias were significantly increased in group 2 compared to group 1. BrdU
      labeling indices for follicular cells and hyperplasias were also significantly
      elevated in group 2 compared to group 1. Electron microscopic examination of
      thyrotrophs in the anterior pituitary in groups 1 and 2 revealed dilated rough ER
      cisternae with intracisternal dense granules. The number of intracytoplasmic
      secretory granules in group 2 was moderately decreased compared to group 1.
      Therefore, the results of the present study suggest that it may be possible to
      enhance production of thyroid neoplastic lesions by intermittent treatment.

PMID- 7585458
TI  - Effect of beta-carotene on the expression of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase in rat liver.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), is a rate
      limiting enzyme in the biosynthesis of not only cholesterol but also a variety of
      non-sterol isoprenoids. It is subjected to multivalent feedback suppression by
      transcriptional and post-transcriptional control mechanisms mediated by sterols
      and non-sterol substances. In the present study, the effect of a plant
      isoprenoid, beta-carotene, on the expression of HMG-CoA reductase in rat liver
      was investigated. In control rats the hepatic levels of mRNA transcripts of HMG
      CoA reductase increased following 2/3 partial hepatectomy with two peaks, one at
      8 h and the other at 24 h. Administration of the carotenoid (70 mg/kg, given
      every alternate day for 3 consecutive weeks) partially inhibited the increase in
      the transcript level with a 50% reduction at 8 h and 30% reduction at 24 h post
      partial hepatectomy. Nuclear run-off assays with nuclei isolated from the resting
      liver and from livers of control rats and rats exposed to beta-carotene for 3
      consecutive weeks and killed 8 h after partial hepatectomy indicated that beta
      carotene did not inhibit the rate of transcription of HMG-CoA reductase gene.
      These observations suggest that beta-carotene regulates the expression of HMG-CoA
      reductase by some post-transcriptional mechanisms.

PMID- 7585460
TI  - Increasing development of pepsinogen-altered pyloric glands and adenocarcinoma in
      glandular stomach of analbuminemic rats.
AB  - The susceptibility of pepsinogen-altered pyloric glands (PAPG) and neoplastic
      glandular stomach lesions induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG)
      and catechol or sodium cholate in Nagase analbuminemic rats (NAR) was compared to
      Sprague-Dawley rats (SD). Male NAR and SD rats were given a single dose of 80
      mg/kg body weight of MNNG by gastric intubation and, 2 weeks later, fed basal
      diet containing 0.8% catechol or 0.3% sodium cholate for 18 weeks. The animals
      were killed at the end of week 20 or after maintenance on basal diet at week 60.
      The number of pepsinogen-altered pyloric glands at week 20 was significantly (P <
      0.001) higher in NAR fed either catechol or sodium cholate compared with SD rats.
      At week 60, adenomatous hyperplasias and adenocarcinomas were observed in 7 (88%;
      P < 0.01) and 3 (38%; P < 0.01) of 8 NAR fed catechol and in 4 (22%) and 0 of 18
      SD rats, respectively. The results show that the frequency of PAPG in NAR and SD
      rats is related to the susceptibility to glandular stomach carcinoma. PAPG is a
      useful endpoint lesion for evaluation of gastric carcinogenicity in a 20-week
      carcinogenicity test, and NAR are sensitive for glandular stomach carcinogenesis.

PMID- 7585462
TI  - Involvement of folic acid in the synthesis of membrane-associated nucleotide
      sugars by normal and transformed mouse fibroblasts.
AB  - A plasma-membrane-containing fraction isolated from Swiss mouse (3T3) fibroblasts
      was found to contain uridine diphosphate sugars and methyl-uridine diphosphate
      (mUDP) sugars. The synthesis of the mUDP sugars by membrane preparations of
      normal and transformed 3T3 cells occurred from the intrinsic membrane uridine
      diphosphate sugars + methylenetetrahydrofolic acid. Compared to the normal 3T3
      cells, the synthesis of mUDP sugars by the transformed 3T3 cells was reduced by
      49%. It is proposed that the plasma-membrane-associated mUDP sugars may be
      essential for normal cell growth.

PMID- 7585464
TI  - Precise mapping of t(12;14) leiomyoma breakpoint on chromosome 14 between D14S298
      and D14S540.
AB  - Uterine leiomyoma is a common tumor of smooth muscle cell origin often
      characterized by the presence of a balanced t(12;14)(q13-15;q24.1) chromosomal
      translocation. This breakpoint on chromosome 14 had previously been placed
      between the markers SPTB and D14S77, a region estimated to span 7 cM. In this
      study we have used a meiotic breakpoint mapping panel to construct a high
      resolution genetic map of this interval. Markers that mapped within this interval
      were used to analyze DNA from a somatic cell hybrid containing the t(12;14)
      translocated chromosome. The results of this analysis localize the t(12;14)
      breakpoint on chromosome 14 between D14S298 and D14S540, between which no meiotic
      recombination was detected. This sets the stage for identifying the gene(s)
      disrupted by the chromosomal translocation by defining the markers that flank the
      translocation breakpoint.

PMID- 7585461
TI  - Increased p53 site-specific DNA binding in cells producing mutant p53.
AB  - Chemotherapeutic and DNA-damaging agents were found to increase p53 site-specific
      DNA binding in human breast and rat liver epithelial WBrasII cells which produce
      mutant p53. Increased p53 site-specific DNA binding by chemotherapeutic or DNA
      damaging agents was also induced in transfected Saos-2 cells producing wild type
      or transforming mutant p53. Therefore, exposure of cells containing a
      transforming p53 mutant to chemotherapeutic or DNA-damaging agents may
      potentially enhance their transformation state and tumorigenic potential.

PMID- 7585465
TI  - Bi-directional stimulation of adherence to extracellular matrix components by
      human head and neck squamous carcinoma cells and endothelial cells.
AB  - Head and neck squamous cell carcinoma (HNSCC) cultures were established from two
      patients to determine if cancer and endothelial cells bi-directionally regulate
      their adherence to extracellular matrix components (ECM), an important process
      for tumor vascularization and metastasis. Soluble products from endothelial cells
      transiently enhanced adherence by HNSCC to ECM and increased surface levels of
      beta 1 and beta 4 integrins, although not beta 3. HNSCC products enhanced
      endothelial cell adherence to fibronectin and laminin, and beta 1 and beta 4
      expression. These data show bi-directional enhancement of adherence to ECM and
      integrin expression among endothelial and tumor cells, which may facilitate
      metastasis and neovascularization.

PMID- 7585463
TI  - Growth inhibition and regression of human prostate and breast tumors in athymic
      mice by tea epigallocatechin gallate.
AB  - The human prostate cancer cell lines, PC-3 (androgen-insensitive) and LNCaP 104-R
      (androgen-repressed) were inoculated subcutaneously into nude mice to produce
      prostate tumors. Intraperitoneal injection of green tea (-)epigallocatechin-3
      gallate but not structurally related catechins, such as (-)epicatechin-3-gallate,
      inhibited the growth and rapidly reduced the size of human prostate tumors in
      nude mice. (-)Epigallocatechin-3-gallate also rapidly inhibited the growth of
      tumor growth formed by the human mammary cancer cell line MCF-7 in nude mice. It
      is possible that there is a relationship between the high consumption of green
      tea and the low incidence of prostate and breast cancers in some Asian countries.

PMID- 7585467
TI  - Cathepsin B, L, and D activities in colorectal carcinomas: relationship with
      clinico-pathological parameters.
AB  - Cathepsins, which are secreted by tumour and/or stromal cells, are thought to be
      involved in the degradative processes of tumour invasion and metastasis. The
      purpose of our study was to compare the cytosolic content of cathepsin B, L, and
      D in a series of matched malignant and adjacent normal colorectal tissues.
      Further we attempted to correlate these different proteinase values to classical
      clinico-pathological prognostic variables. Cathepsin B, L, and D activities were
      higher in tumour tissues than in normal mucosa (P < 10(-6), P < 0.004, P < 0.004,
      respectively) with median tumour/normal ratios of 7.9, 5.9, and 1.4,
      respectively. We found no difference in cathepsin B, L, and D activities either
      as a function of gender (except for cathepsin B values), age at time of surgery,
      tumour site, tumour differentiation, tumour stage (TNM or Astler-Coller staging
      system) or whether or not we found a mucinous component. Based on our data,
      cathepsin B seems to be the most discriminant parameter of the three proteinases
      that we studied, suggesting that cathepsin B expression may be of critical value
      in the progression of colorectal cancers.

PMID- 7585466
TI  - Tubercidin stabilizes microtubules against vinblastine-induced depolymerization,
      a taxol-like effect.
AB  - A sensitive assay for the detection of microtubule-stabilizing agents [1] was
      used to screen an extensive collection of cyanobacterial and microalgal extracts.
      The hydrophilic extract of the cyanobacterium, Plectonema radiosum (UH isolate IC
      70-1), exhibited microtubule-stabilizing activity. Bioassay-directed purification
      of the active compound yielded tubercidin (7-deazaadenosine), a potent cytotoxic
      nucleoside analog. Further studies revealed that tubercidin protected a
      population of cellular microtubules against vinblastine-induced depolymerization,
      a microtubule-stabilizing, taxol-like effect. The microtubule-stabilizing effect
      of tubercidin is dose dependent and limited by the cytotoxicity of the agent.
      Tubercidin represents another natural product that interacts with microtubules
      and is one of the few to cause microtubule stabilization.

PMID- 7585468
TI  - Tobacco-specific nitrosamines in some Nigerian cigarettes.
AB  - Ten popular brands of cigarettes on the Nigerian market were analyzed for tobacco
      specific nitrosamines (TSNA) in tobacco and in mainstream smoke, as well as
      nitrate in tobacco. TSNA was analyzed using a gas chromatography/thermal energy
      analyzer (GC-TEA), while nitrate was determined spectrophotometrically as nitrite
      following on-line reduction with copper, diozatization with sulfanilamide and
      coupling with N-(1-naphthyl) ethylene diamine to form an azo dye. In mainstream
      smoke, the concentration of NNN, NAB/NAT and NNK were respectively, between 8 and
      90 ng, 10 and 65 ng, and between 15 and 72 ng/cigarette. Preformed NNN ranged
      between 64 and 565 ng/cigarette, while preformed NAB/NAT and NNK ranged
      respectively from 109 to 476 ng/cigarette, and from 55 to 317 ng/cigarette.
      Nitrate levels ranged between 1.5 and 6.1 mg/g tobacco. In general, the results
      indicate that the TSNA content of Nigerian cigarettes are within the range found
      for European and American cigarettes.

PMID- 7585469
TI  - Growth arrest associated changes of mRNA levels in breast cancer cells measured
      by semi-quantitative RT-PCR: potential early indicators of treatment response.
AB  - To find early and sensitive indicators of treatment response in breast cancer, we
      studied the mRNA levels of proliferation-related genes during growth arrest of
      the human breast cancer cell lines T47D and MCF7. A sensitive reverse
      transcriptase-PCR (RT-PCR) technique was used in order to monitor gene expression
      in small samples of cells. Estrogen-depletion and treatment with tamoxifen
      effectively induced a G1-arrest in both cell lines, accompanied by a decrease of
      the mRNA levels of histone H4, cyclin A, cyclin D1, and c-myc. Cyclin A
      expression decreased most strongly: up to 32-fold within 7 days. The expression
      of c-fos and WAF1 increased during growth arrest. In conclusion, significant
      changes of the levels of proliferation-related mRNAs, induced by growth arrest,
      can be measured in small samples of breast carcinoma cells using RT-PCR.
      Especially the decrease of the cyclin A mRNA level seems a potential early
      indicator of clinical response to tamoxifen therapy in breast cancer patients.

PMID- 7585470
TI  - Increase of a guinea pig natural killer cell (Kurloff cell) during
      leukemogenesis.
AB  - The guinea pig Kurloff cell (KC) is an estradiol-dependent circulating
      mononuclear cell that had natural killer cytotoxic activity in vitro. We studied
      the variation of KC number during the development of transplanted leukemia in
      inbred strain 2 (S2) leukemia-sensitive guinea pigs. Grafts of leukemic cells
      (L2C) produced a significant increase in the number of KC. Leukemia occurred in
      35.5% of non-estrogenized animals and in 18.3% of estrogenized guinea pigs. The
      increased number of KC seems to have antileukemia activity in vivo. This could be
      part of the general phenomenon of cancer resistance in guinea pigs.

PMID- 7585472
TI  - Loss of heterozygosity at 9p and 17q in human laryngeal tumors.
AB  - Recent investigations revealed that the 9p arm and 17q arm of human chromosomes
      harbour tumour suppressor genes (TSGs) with an important role in multistage
      carcinogenesis. At the 9p arm is located the p16 (MTS1) TSG and probably others
      with an effect on various human tumours such as acute lymphoblastic leukaemia,
      bladder cancer, gliomas, malignant mesotheliomas, melanomas and non-small cell
      lung carcinomas. In addition, the 17q arm harbours BRCA1 TSG which is responsible
      for approximately 80% of the familial breast/ovarian cancer cases. In order to
      investigate the implication of these performed a loss of heterozygosity (LOH)
      analysis with 10 polymorphic microsatellite markers (three at the 17q arm
      surrounding the BRCA1 region and seven at the 9p arm). Fourteen of the 17 (82%)
      tumours exhibited deletions at 9p. The highest incidence of LOH (6/13, 46%) was
      found for the marker D9S157 at 9p22. One sample exhibited deletion of all the
      informative markers tested indicating deletion of the complete 9p arm. No
      homozygous deletions were found. LOH at the 17q arm near the BRCA1 locus was
      found in 6 (35%) among 17 specimens. The results of this study indicate that
      allelic deletions at 9p are frequent in the development of laryngeal tumours. The
      highest incidence of LOH was found for the marker D9S157 which is near, but
      distinct from the location of p16 (MTS1) tumour suppressor gene, indicating the
      presence of multiple tumour suppressor genes within this chromosomal region. In
      addition, BRCA1 TSG is implicated in the development of laryngeal tumours.

PMID- 7585471
TI  - Polyamine acetylation in rat brain during N-ethyl-N-nitrosourea-induced cerebral
      carcinogenesis.
AB  - The behavior of cerebral polyamine acetylation was examined in rat brain during N
      ethyl-N-nitrosourea-induced carcinogenesis. Before tumor development, treated
      brains exhibited an enhancement in cytosolic spermidine/spermine N1-acetyl
      transferase activity with concomitant accumulation of N1-acetylspermidine and
      increases in putrescine and spermidine. This indicates a stimulation of the
      interconversion pathway of polyamines into putrescine, an important molecule for
      cell growth. Our data also show the presence of a cytosolic spermidine N8
      acetyltransferase activity in fetal rat brain, with values similar to those
      previously observed in gliomas. The detection of cytosolic spermidine N8
      acetyltransferase activity in tumors may thus represent the expression of a fetal
      gene that does not seem to have a particular function during carcinogenesis.

PMID- 7585474
TI  - Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and
      inhibiting tumor growth.
AB  - It has been recently reported that a diet enriched in n-3 polyunsaturated fatty
      acids reduces the growth of different kinds of tumors as well as the host tissue
      hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH
      130 is a fast growing tumor that causes a rapid and progressive body weight loss
      in the host and tissue waste associated with a hypercatabolic condition. Plasma
      levels of classical hormones and humoral mediators (prostaglandin E2 and tumor
      necrosis factor-alpha) are early perturbed after tumor transplantation
      (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for
      cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein
      degradation rates and alteration of lipoprotein lipase activity mainly account
      for the wasting of protein and adipose mass, respectively. However, the daily
      intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130
      bearing rats was completely ineffective either in preventing tissue waste or in
      reducing tumor growth. The low degree of differentiation and the high growth rate
      of the AH0130 hepatoma probably account for this lack of effect.

PMID- 7585473
TI  - No effect of treatment with carcinogens on cytosine methylation of mitochondrial
      DNA isolated from rat organs by phenol-free alkaline extraction.
AB  - Due to the postulated role of mitochondrial DNA damage in aging as well as in the
      pathogenesis of several chronic degenerative diseases, including tumors, there is
      a need for easy, safe, rapid and inexpensive methods for mitochondrial DNA
      isolation. We propose a simple, 1-day protocol based on alkaline extraction,
      which avoids time-consuming gradient centrifugations and use of toxic phenol.
      This procedure was used for the recovery of mitochondrial DNA from different rat
      organs (liver, kidney, heart, lung, brain and testis). The yield was quite high.
      Purity was sufficient enough to perform restriction analyses with several
      endonucleases. No changes were observed in the structure or methylation patterns
      of -CCGG- sites in liver mitochondrial DNA isolated from rats exposed whole-body
      to mainstream cigarette smoke or treated with the carcinogens benzo[alpha]pyrene,
      2-acetylaminofluorene or diethylnitrosamine.

PMID- 7585475
TI  - Anticancer and antioxidant activity of synthetic chalcones and related compounds.
AB  - Nineteen synthetic chalcones and ten structurally related compounds were
      investigated for their cytotoxic, tumour reducing and antioxidant activities.
      Methyl and hydroxy substituted chalcones were found to be cytotoxic in vitro
      whereas only hydroxy substituted chalcones could reduce ascites tumour in
      animals. Although most of the compounds analysed showed antioxidant activity,
      hydroxy and methyl substituted compounds were found to be the most potent
      antioxidants.

PMID- 7585476
TI  - Passage of X-ray-induced immortal, non-transformed phenotype by DNA-mediated
      transfection.
AB  - To better understand the molecular basis of X-ray-induced carcinogenesis, the
      immortalization step of this multistep process was examined. Primary rat embryo
      cells were X-irradiated in vitro and six clones were isolated. Three of these,
      one designated X-REF-23, were immortal and non-transformed. Transfection of high
      molecular weight DNA from rat X-REF-23 cells into primary mouse cells yielded two
      immortal and non-transformed mouse clones, 1K and 2I. Using a 2.3 kb rat-specific
      repetitive sequence as probe, 1K and 2I were demonstrated to contain rat DNA.
      This transfected DNA was not any of the known immortalization-associated proto
      oncogenes. DNA from 1K was then transfected into primary mouse cells, with or
      without co-transfection of pSV2 neo DNA. Six immortal mouse clones were isolated
      and confirmed to contain rat sequences. In conclusion, the immortal phenotype can
      be transferred by DNA transfection.

PMID- 7585477
TI  - An assay for the determination of reduced methotrexate accumulation in cells
      displaying limited viability in vitro.
AB  - Amongst the mechanisms known to mediate resistance to methotrexate (MTX), a major
      component in the treatment of childhood leukemia, reduced drug accumulation
      appears to have direct clinical relevance. However, due to the poor viability of
      patient-derived acute lymphoblastic leukemia cells in vitro, determination of
      this parameter in clinical samples is associated with a number of difficulties.
      We have therefore developed an assay for reduced MTX accumulation, which controls
      for the metabolic state of the cell population under study by utilizing
      accumulation of the nucleoside thymidine as an independent indicator of this
      parameter. To establish this assay, we have utilized pediatric leukemic cell
      populations maintained as xenografts in nude mice, which, despite displaying
      sensitivity to MTX, demonstrated reduced accumulation of MTX when assayed using
      standard methodology. When accumulation of MTX by such cell populations was
      expressed, however, relative to their accumulation of thymidine, MTX accumulation
      was shown to be equal to that of drug-sensitive CCRF-CEM cells maintained in long
      term culture. In contrast, significantly less MTX was accumulated, in this assay,
      by xenografted cell populations with demonstrated resistance to MTX. Identical
      results were obtained using either fresh or cryopreserved cells. The data thus
      indicate that by controlling for variable metabolic status of leukemic cells, it
      is possible to accurately assess MTX accumulation in leukemic samples displaying
      limited viability in culture.

PMID- 7585478
TI  - Increased reproductive tract tumors in the female offspring of mice fed a high
      fat diet during the fetal stage of pregnancy.
AB  - In a previous study, female offspring of mice consuming a high fat diet
      throughout pregnancy developed reproductive system tumors and tumor metastases
      with a frequency significantly higher than offspring of mice on a low fat diet.
      To test for the sensitive period more specifically, the feeding of a high fat
      diet was restricted to the fetal period of pregnancy in the present experiment.
      The offspring were raised to terminal illness and autopsied. The total number of
      ovarian, uterine and mammary tumors was 14 among 74 mice exposed prenatally to
      low fat and 34 among 75 mice exposed prenatally to high fat (P < 0.002). In mice
      exposed to high fat during the fetal period 13 tumors produced metastases, but no
      metastases were identified after exposure to low fat (P < 0.001). Thus, a
      maternal diet high in fat during the fetal period of pregnancy was sufficient to
      increase reproductive system tumors and metastases in the female offspring.

PMID- 7585479
TI  - Crocetin protects against oxidative damage in rat primary hepatocytes.
AB  - Crocetin is a major component in the fruit of Gardenia jaminoides Ellis, a
      Chinese herbal medicine. Its protective action and mechanism against oxidative
      damage were investigated and mechanism against oxidative damage were
      investigated. Reactive oxygen species (ROS) were generated enzymatically in the
      xanthine-xanthine oxidase (X/XO 5 microM/0.01 u/ml) system and non-enzymatically
      in the paraquat (PQ 5 mM) system. Both systems increased leakage of lactate
      dehydrogenase (LDH) and alanine transaminase (ALT) in rat primary hepatocytes,
      but the hepatotoxicity was significantly suppressed on pretreatment with crocetin
      (10, 20 microM). Crocetin decreased formation of malondialdehyde (MDA) as an
      index of lipid peroxidation induced by ROS. The oxyradical generation by X/XO or
      PQ caused DNA damage evaluated with unscheduled DNA synthesis (UDS) in rat
      primary hepatocytes. The addition of crocetin decreased genotoxicity evaluated
      with UDS in both systems. The data showed that crocetin also inhibited the
      formation of superoxide anion in the X/XO system and bleached the free radical 1,
      1-diphenyl-2- picrylhydrazyl (DPPH). The protective action of crocetin operated
      via quenching of the superoxide anion and/or free radical.

PMID- 7585480
TI  - Effect of osteoblast supernatants on cancer cell migration and invasion.
AB  - Malignant tumor cells of different origin seem to have preferential sites for
      metastasis. Breast cancer, prostate cancer and certain melanomas have bone as one
      of their preferential targets for metastasis. Bone is continuously being
      remodelled, a process largely controlled by local growth factors. A possible
      explanation for malignant cell recruitment to bone is that osteoblast products,
      directly secreted or released from the matrix by osteoclast resorbing activity,
      are able to stimulate cancer cell migration. To test this hypothesis we have
      utilized an in vitro system of differentiating osteoblasts which in culture
      progress all the way to the formation of mineralized nodules. Conditioned media
      obtained from these osteoblast cultures at different stages were able to induce
      chemotactic migration and invasion of both melanoma and breast cancer cells. The
      migratory and invasive phenotype was accompanied by enhanced gelatinolytic
      activity of osteoblast stimulated cancer cells. Our data suggest that osteoblasts
      secrete potent factors able to direct tumor cell migration towards remodelling
      bone.

PMID- 7585481
TI  - Studies on the mechanism of sulofenur and LY295501 toxicity: effect on the
      regulation of cytosolic calcium in relation to cytotoxicity in normal and
      tumorigenic rat kidney cell lines.
AB  - Treatment of NRK-52E (normal) and H/1.2-NRK-52E (Harvey-ras transfected NRK-52E)
      rat kidney epithelial-like cells with two Eli Lilly antitumor compounds,
      sulofenur and LY295501 (15.6 microM-1000 microM) resulted in concentration- and
      time-dependent cell killing. Cytosolic Ca2+ became elevated in both cell lines in
      the presence of extracellular Ca2+ but only minimally in its absence. Both drugs
      were more toxic to the tumorigenic cells than to the normal cells, but LY295501
      was significantly more toxic to both cells. The similarity in toxic response by
      both cell lines suggests a similar mechanism of toxic action for both drugs.
      Since LY295501 is highly toxic to tumorigenic cells but has a manageable dose
      limiting toxicity it shows excellent potential for use in chemotherapy.

PMID- 7585486
TI  - 20th Muntendam Award.

PMID- 7585484
TI  - Flow injection analysis quantifies multidrug resistance phenotype.
AB  - Flow injection analysis (FIA? of DNA damage, repair and drug accumulation was
      employed to examine the relation between DNA damage, drug resistance and cell
      survival. Resistant sublines to adriamycin (P388/ADR), mitoxantrone (P388/MTN)
      and drug sensitive (P388/S) leukemic cells were exposed to different
      concentrations of adriamycin. The subtle difference in tumor response between
      sensitive and resistant cells was well differentiated and the results were
      comparable with other methods of measuring DNA strand-break and repair. Drug
      concentrations as low as 5 x 10(-11)M could be measured by FIA. In addition the
      method also enables assessment of cross-resistance/sensitivity. The speed,
      sensitivity and reproducibility make FIA a good technique for routine monitoring
      of tumor cell response to DNA damaging agents.

PMID- 7585483
TI  - Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumour
      angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells
      in mice.
AB  - We examined the inhibitory effect of an aqueous extract (referred to as KM-110)
      from Viscum album coloratum, a Korean mistletoe, on tumour metastasis produced by
      highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma
      and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis
      models in syngeneic mice. In experimental metastasis of B16-BL6 and colon 26-M3.1
      cells, intravenous (i.v.) administration of KM-110 (100 micrograms/mouse) 1 day
      after tumour inoculation significantly inhibited lung metastasis of both tumour
      cells. The administration of KM-110 also exhibited a therapeutic effect on liver
      and spleen metastasis of L5178Y-ML25 lymphoma cells. Furthermore, in spontaneous
      metastasis of B16-BL6 melanoma cells, multiple administration of KM-110 into
      tumour-bearing mice resulted in significant inhibition of lung metastasis by
      tumour cells, as well as the suppressive activity to the growth of primary
      tumour. In in vivo analysis for tumour-induced angiogenesis, the i.v.
      administration of KM-110 suppressed tumour growth and inhibited the number of
      blood vessels oriented towards the tumour mass. In a bioassay, the culture
      supernatant (KM-110-treated medium) of murine peritoneal macrophages that had
      been stimulated with KM-110 (1-10 micrograms/ml) for 30 min followed by 24 h
      incubation in fresh medium showed a strong tumour necrosis factor-alpha (TNF
      alpha) activity. In addition, KM-110-treated medium significantly inhibited the
      growth of in vitro cultures of rat lung endothelial (RLE) cells. These results
      suggested that the extract of Korean mistletoe inhibits tumour metastasis caused
      by haematogenous as well as non-haematogenous tumour cells, and that its
      antimetastatic effect results from the suppression of tumour growth and the
      inhibition of tumour-induced angiogenesis by inducing TNF-alpha.

PMID- 7585485
TI  - Effects of vitamin D3 derivatives on growth, differentiation and apoptosis in
      tumoral colonic HT 29 cells: possible implication of intracellular calcium.
AB  - In addition to the effects on tumor cell differentiation and growth inhibition,
      vitamin D3 derivatives may exert other cellular actions such as the inhibition of
      angiogenesis or the induction of apoptosis. In this study, we demonstrated that
      vitamin D3 derivatives, 1,25-dihydroxyvitamin D3, the natural derivative and Ro
      23-7553, a synthetic derivative, displayed complex effects in tumoral colonic HT
      29 cells. Indeed, as a function of the stage of culture, they induced either
      apoptosis or differentiation along with a constant cell cycle blockade in G1.
      Intracellular calcium analysis indicated that treatment resulted in disturbance
      in the distribution of calcium suggesting a possible role for intracellular
      calcium in the observed effects. The association of 9-cis-retinoic acid, the
      ligand of RXR, with vitamin D3 derivatives modified the demonstrated effects,
      indicating in our model, a preferential effect of vitamin D3 derivatives via the
      heterodimeric form of the receptor.

PMID- 7585482
TI  - The mRNA overexpression of inflammatory enzymes, phospholipase A2 and
      cyclooxygenase, in the large bowel mucosa and neoplasms of F344 rats treated with
      naturally occurring carcinogen, 1-hydroxyanthraquinone.
AB  - Inflammation has been considered to be related to carcinogenesis. Previously, we
      demonstrated that 1-hydroxyanthraquinone (1-HA), a naturally occurring
      carcinogen, induced severe inflammation such as ulcerative colitis in colonic
      mucosa. We also showed that indomethacin inhibited the tumorigenicity of 1-HA. In
      this study, we examined the expressions of major enzymes in arachidonic acid
      cascade related to inflammation in the colon mucosa of rats treated with 1-HA.
      After the treatment of 1% 1-HA diet, colon lesions were observed and RNA was
      extracted from mucosa and neoplasms. The mRNA expressions of group II
      phospholipase A2, cyclooxygenase-2 and 5-lipoxygenase, were examined by using a
      reverse transcriptase polymerase chain reaction. The expressions of phospholipase
      A2 and cyclooxygenase were significantly increased in non-neoplastic mucosa in
      rats treated with 1-HA compared with those in control rats. The expressions in
      the neoplasms induced by 1-HA were also increased. Phospholipase A2, especially,
      was much higher in the neoplasms than in non-neoplastic mucosa. However, the
      expression of 5-lipoxygenase showed no change in the non-neoplastic mucosa and
      neoplasms of rats treated with 1-HA, compared with that in control rats. These
      findings suggest that the inflammation induced by 1-HA may be related to the
      metabolites through a cyclooxygenase pathway, which indicates a prostaglandin
      synthesis, but not through a lipoxygenase pathway, which indicates a leukotriene
      synthesis in arachidonic acid cascade.

PMID- 7585487
TI  - Need for overnight respite for primary caregivers of hospice clients.
AB  - A major reason for admission of community hospice clients to the hospital is
      exhaustion of the primary caregiver. One way to prevent the problem of caregiver
      exhaustion may be the use of trained laypersons who remain overnight with the ill
      person, thereby providing respite that allows the caregiver to sleep. A survey
      was conducted to assess primary caregivers' appraisal of the need for overnight
      respite and their willingness to receive this support from trained laypersons.
      Thirty-seven primary caregivers, who used the services of a community hospice,
      were interviewed to determine primary caregivers' appraisals of problems,
      resources, and needs. Ten (27%) primary caregivers reported usually receiving 0
      to 4 of sleep per night and 27 (73%) reported receiving > 4 h. Sleep time was
      described by the majority as insufficient, but insufficient, sleep was
      statistically not a main reason for hospital admission. Findings suggested that
      those in the 0- to 4-h category were more vulnerable to exhaustion. Seventy
      percent of respondents indicated that they would use the services of a trained
      layperson for overnight respite and an additional 6% indicated that they would
      under certain conditions.

PMID- 7585488
TI  - Stories about becoming a hospice nurse. Reasons, expectations, hopes and
      concerns.
AB  - Two months after the opening of Sweden's first purpose-built free-standing
      hospice, 19 nurses were asked to narrate their reasons, expectations, hopes, and
      concerns about their future work as hospice nurses. The stories were analyzed
      using a phenomenological-hermeneutic approach inspired by the philosophy of
      Ricoeur. The tension between endurance and enjoyment seems to be the essential
      feature of the nurses' stories. The nurses who were experienced in terminal care
      hope and expect to enjoy being hospice nurses, provided they are able to give
      good terminal care, that is, nursing care that is experienced as being
      meaningful. Those nurses who are inexperienced in terminal care hope and expect
      that they will be able to give and to grow as people and to develop as
      professionals, but do not yet know what to make of their experiences. Possible
      implications of the nurses' reasons, expectations, hopes, and concerns are
      discussed, and an understanding of the tension between endurance and enjoyment of
      being a hospice nurse is presented.

PMID- 7585489
TI  - Hope and quality of life, two central issues for cancer patients: a theoretical
      analysis.
AB  - During the past years, the number of people diagnosed with cancer has increased.
      Cancer can be a threat to life itself, as well as to the individual's perception
      of the quality of life. The question of what contributes a clinically significant
      change or difference in perceived quality of life remains unanswered. Hope is
      frequently referred to as important for coping with a disease such as cancer.
      Hope enables people to cope with difficult and stressful situations and
      suffering. Nevertheless, hope is seldom stressed in definitions of the quality of
      life for cancer patients and discusses the relationship between hope and quality
      of life, and hope can be regarded as a coping strategy. From existing theory,
      hope can be seen as a variable positively contributes to the experience of
      quality of life. Future research should empirically explore to what extent hope
      contributes to the adaptive process that maintains the quality of life at an
      acceptable level despite having cancer.

PMID- 7585490
TI  - What kind of social support do cancer patients get from nurses?
AB  - Health care workers have been identified as sources of social support for cancer
      patients. However, little is known about the type of support patients receive
      from nurses. The primary purpose of this study was to determine if patients
      perceived differences in how often they received different types of support from
      nurses. The dimensions of support assessed were based on House's
      conceptualization of social support as made up of four components: emotional,
      informational, instrumental, and appraisal. A secondary purpose was to determine
      how satisfied the patients were with the nursing care they received while
      hospitalized. Sixty-six patients completed a questionnaire containing a 23-item
      self-report scale that measured how often they received specific types of support
      from nurses. The questionnaire also contained a seven-item self-report scale that
      measured how satisfied they were with the nursing care they received. Patients
      reported receiving significantly more instrumental and less appraisal support
      than other types of support (p < 0.008). Satisfaction with nursing care was
      significantly related to the amount of support they perceived receiving (p <
      0.01). Implications for the importance of affirming the personal worth of cancer
      patient's as a part of routine nursing care are discussed and intervention
      strategies suggested.

PMID- 7585491
TI  - A program for the home care of patients with a symptomatic malignant terminal
      disease.
AB  - The goal of this program was to identify problems in patients with symptomatic
      malignant terminal disease relating to the improvement of their care at home. A
      program was developed consisting of guidelines and instructions which built on
      the previous training of the family members assuming their care. Patient needs
      assessment was performed to identify the major problems afflicting patients.
      Problems were described by nursing diagnoses using the classification system of
      altered functional patterns. Based on their problems, family members were trained
      so that they could offer patients more adequate care and attention in their
      homes. The effectiveness of the program was evaluated, as was its impact on the
      patients themselves and their families.

PMID- 7585492
TI  - Functions and preferred methods of receiving information related to radiotherapy.
      Perceptions of patients with cancer.
AB  - A convenience sample of 83 patients with cancer were interviewed before and/or
      after a full course of radiotherapy, with 36 patients interviewed both times, to
      determine their perceptions about the functions served by the information
      received from standard care personnel. Patients indicated the preferred sources
      of receiving information. The results indicate that information served three main
      functions. Active participation was the most frequently cited function. There was
      no difference by gender, age, education, or socio economic status (SES) in type
      of functions cited. Disadvantages in receiving information were rarely cited but
      included receiving bad news and inaccurate or vague information. Many stated that
      they nevertheless still wanted the information. Verbal communication, especially
      form the physician, followed by written material, was the most popular choice for
      receiving information at treatment. Written material was more frequently cited as
      the preferred type of information at posttreatment. Nurses were mentioned as an
      information source more frequently at posttreatment than at pretreatment.
      Implications of the findings for practitioners working with patients with cancer
      are discussed.

PMID- 7585493
TI  - Fatalism among elderly African Americans. Effects on colorectal cancer screening.
AB  - The goal of increasing participation in fecal occult blood testing (FOBT) for
      elderly African Americans is a national priority. Fatalism is believed to be a
      barrier to screening among this population. Fatalism is the belief that death is
      inevitable when cancer is present. The Powe Fatalism Model guided this
      descriptive, correlational study that reports on the relationship between race
      and fatalism, as well as the relationship between fatalism and participation in
      FOBT. Participants (N = 192) were recruited from randomly selected congregate
      meal sites. The majority of participants were African American, female, had
      minimal education, and minimal incomes. Elderly African Americans were
      significantly more fatalistic than elderly white participants and less likely to
      participate in FOBT. Not only was fatalism a significant predictor of FOBT, but
      it remained the only significant predictor of FOBT, but it remained the only
      significant predictor even when factors such as age, poverty, and education were
      controlled. Nursing science must accept the challenges of promptly identifying
      fatalistic individuals and the development of interventions to counteract its
      influence.

PMID- 7585494
TI  - A combined analysis of a toothbrush, foam brush, and a chlorhexidine-soaked foam
      brush in maintaining oral hygiene.
AB  - Oral hygiene in immunocompromised patients is important in preventing oral
      infection and may be important in preventing systemic infections. By mechanically
      reducing bacterial plaque levels in the oral cavity, the risk of infection may be
      reduced. Foam brushes have been shown to be ineffective in controlling plaque
      levels and gingivitis. In a 2-week trial, we demonstrated that using a foam brush
      soaked in chlorhexidine reduces plaque and controls gingivitis as effectively as
      using a toothbrush. Foam brushes soaked in chlorhexidine should be used when
      toothbrushing cannot be performed.

PMID- 7585495
TI  - Biotherapy module. II. Overview of biotherapy.

PMID- 7585496
TI  - Emergence of adenomatous aberrant crypt foci (ACF) from hyperplastic ACF with
      concomitant increase in cell proliferation.
AB  - To investigate the relationship between aberrant crypt foci (ACF) and colon
      neoplasia in colorectal carcinogenesis, we evaluated 433 ACF, which were
      collected from the grossly normal mucosa of surgical specimens from 57 patients
      with colorectal cancer. The ACF ranged in size from 3 to 412 aberrant
      crypts/focus. Large ACF (> or = 50 crypts/focus) comprised 25% of the total ACF
      studied. Histopathologically, 65% (67 of 103) of large ACF were diagnosed as
      hyperplasia, 10% (10 of 103) as adenoma, and 1% (1 of 103) as within normal
      colorectal mucosa. The remaining 24% (25 of 103) were diagnosed as "stage I
      abnormality crypts," which were characterized by their extension of the
      proliferative compartment to the surface of crypts but with no changes in the
      major site of proliferation, as designated by E. E. Deschner [Pathol. Annu., 18
      (Part 1): 205-219, 1983]. Of the 25 stage I abnormality ACF, 7 ACF coexisted with
      hyperplasia. Of 10 adenomatous ACF, two coexisted with stage I abnormality
      crypts. A K-ras codon 12 mutation was identified in 85% (93 of 109) of large ACF.
      The proliferative activity of stage I crypts was significantly higher than that
      of hyperplastic crypts in the same ACF. These observations suggest that some
      hyperplastic ACF may develop into adenomatous ACF by way of stage I abnormality
      ACF with concomitant acquisition of higher proliferative activity through some
      genetic and/or epigenetic changes.

PMID- 7585497
TI  - Tumor growth inhibition mediated by lymphotoxin: evidence of B lymphocyte
      involvement in the antitumor response.
AB  - The antitumor effect of lymphotoxin (LT) and the underlying cellular mechanism
      were analyzed. To achieve an increased local concentration of LT at the site of
      tumor growth, which mimics the physiological fashion of cytokine action, we
      transfected the murine plasmacytoma J558L cells with a human LT expression
      plasmid and selected several clones that produce varying levels of LT for
      analysis of their tumorigenicity. The LT produced by the transfected J558L cells
      effectively suppressed tumor growth in syngeneic BALB/c mice without any obvious
      side effects. This antitumor function is indirect and LT specific, because the
      tumor cells did not show altered growth kinetics after the gene transfer in
      vitro, and tumor growth inhibition in vivo could partially be reversed by an anti
      LT mAb. In nude mice, LT producing tumors were initially suppressed, but most
      mice developed a tumor at the end of the study. However, the requirement of T
      cells for complete tumor rejection could be compensated for by higher amounts of
      LT secretion. Furthermore, the antitumor activity of LT seems to involve B
      lymphocytes in the absence of functional T lymphocytes since a significant
      difference existed between tumor growth of J558-LT cells in nude and in SCID
      mice. LT-producing tumors but not parental tumors were massively infiltrated by
      B220+ cells in nude mice. The secretion of LT by tumor cells also induced a heavy
      infiltration of Mac-1+ and Mac-3+ cells and a moderate infiltration of Gr-1+
      cells, both in nude and in SCID mice. Together, LT-producing J558L cells are
      rejected by a complex immunological mechanism, which seems to involve T as well
      as B and other cells. This distinguishes LT from a number of other cytokines
      analyzed in analogous experiments.

PMID- 7585498
TI  - Treatment of human malignant meningiomas by G207, a replication-competent
      multimutated herpes simplex virus 1.
AB  - We have demonstrated that replication-competent attenuated mutants of herpes
      simplex virus type 1 (HSV-1) have therapeutic potential for malignant gliomas.
      Moreover, a recently described multiple mutant HSV (termed G207) has properties
      which may allow human clinical trials. G207 is able to replicate within and kill
      cells from three human malignant meningiomas in cell culture. In nude mice
      harboring s.c. human malignant meningioma (F5), G207 can inhibit growth in a dose
      dependent fashion. In nude mice harboring intracranial subdural human malignant
      meningioma (F5), one injection of G207 caused significantly decreased tumor
      growth and one apparent cure with neither neurological dysfunction nor
      pathological changes in the surrounding brain. These results suggest that G207
      should be considered for therapeutic trials in the treatment of malignant
      meningioma refractory to currently available therapies.

PMID- 7585500
TI  - Elevated DNA repair capacity is associated with intrinsic resistance of lung
      cancer to chemotherapy.
AB  - Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy
      even without previous drug treatment, as opposed to small cell lung cancer
      (SCLC), which is initially responsive to chemotherapy. The mechanisms of this
      intrinsic resistance are unknown. This study was designed to investigate the role
      of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary
      N-SCLC cell cultures and established cell lines were examined and compared to
      SCLC cell lines established previously from untreated patients. The overall DNA
      repair capacity was estimated by the ability of cells to reactivate the pRSV-CAT
      plasmid damaged by cisplatin ("host cell reactivation" assay). Cytotoxicity was
      determined for cisplatin in vitro. N-SCLC cells were found to be significantly
      more resistant to cisplatin than SCLC cell lines isolated from untreated patients
      (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged
      with cisplatin and transfected into cells was higher in N-SCLC cells than in SCLC
      cells originating from patients who were untreated previously (P < 0.05).
      Correlation was also observed between chloramphenicol acetyltransferase activity
      and intrinsic resistance to cisplatin. However, no significant difference was
      observed between primary N-SCLC cultures and established cell lines. This study
      indicates that elevated DNA repair capacity is associated with drug resistance in
      lung cancer and suggests that modulation of DNA repair mechanism(s), such as the
      incorporation of specific DNA repair inhibitor(s) in therapeutic regimens, may
      help to improve therapeutic strategies of N-SCLC.

PMID- 7585499
TI  - Correlation of high lactate levels in human cervical cancer with incidence of
      metastasis.
AB  - Tissue concentrations of ATP, glucose, and lactate in cervical cancer biopsies
      that were taken before a conventional radiation treatment were imaged
      quantitatively with a bioluminescence technique. Concomitantly, a number of
      clinically relevant data, such as local tumor control, patient survival,
      metastatic spread, etc., were documented. There was no correlation between
      staging or grading and any of the metabolic parameters measured. Local
      correlations between ATP, glucose, and lactate on a pixel-to-pixel basis were
      generally positive, with respective Spearman's correlation coefficients being
      lower in patients without clinically documented metastasis compared to those with
      metastatic spread. Lactate concentrations were significantly higher and scattered
      over a wider range in tumors with metastatic spread in comparison to malignancies
      in patients without metastasis. Thus, high local lactate levels of > or = 20
      mumole/g appear to be associated with a high risk of metastasis, at least in the
      ten human cervical tumors investigated to date.

PMID- 7585501
TI  - High cytokine production and effective antitumor activity of a recombinant
      vaccinia virus encoding murine interleukin 12.
AB  - We have constructed a recombinant vaccinia virus (recVV), vKT0334 mIL-12,
      containing the genes encoding the p35 and p40 subunits of murine interleukin-12
      (mIL-12). In vitro experiments demonstrated that vKT0334 mIL-12 efficiently
      infected a variety of murine and human tumor cell lines and produced very high
      amounts (1.5 micrograms/10(6) cells/24 h) of biologically active mIL-12. Mice
      injected s.c. with 10(6) MCA 105 sarcoma cells, followed by injection at the same
      site with saline or a control recVV, vKT033, containing no mIL-12 genes, all
      developed progressively growing tumor, whereas 60% of animals injected with
      vKT0334 mIL-12 remained tumor free (P < 0.0005). Furthermore, tumor growth was
      significantly reduced in the remaining mice treated with vKT0334 mIL-12 that did
      develop tumor compared with mice treated with vKT033 (P < 0.03) or saline (P <
      0.0001). We conclude that recVV expressing high levels of mIL-12 offers an
      effective in vivo method of cytokine gene delivery and expression in tumors with
      subsequent antitumor effect.

PMID- 7585503
TI  - Regression of established tumors in mice mediated by the oral administration of a
      recombinant Listeria monocytogenes vaccine.
AB  - We have shown previously that Listeria monocytogenes, a gram-positive,
      facultative intracellular bacterium, is a potent vector for targeting tumor
      specific antigens to the immune system. After parenteral administration, we
      observed protection against both renal and colorectal mouse tumors and regression
      of established renal tumors. In the present study, we have exploited the fact
      that the normal route of infection of this organism is through the gut. We show
      that an L. monocytogenes recombinant that expresses a model tumor antigen is an
      effective cancer immunotherapeutic agent when delivered orally in that it causes
      regression of established, macroscopic mouse renal and colorectal tumors
      expressing the same antigen.

PMID- 7585502
TI  - Transfection of complementary DNAs for the heavy and light subunits of human
      gamma-glutamylcysteine synthetase results in an elevation of intracellular
      glutathione and resistance to melphalan.
AB  - Although glutathione (GSH) has long been implicated in resistance to certain
      common chemotherapeutic agents, including alkylating agents, platinum analogues,
      and doxorubicin, evidence establishing a direct role in the resistant phenotype
      has been lacking. We cotransfected COS cells with the cDNAs for the two subunits
      of gamma-glutamylcysteine synthetase (GCS), which catalyzes the rate-limiting
      step in the de novo synthesis of GSH and is itself up-regulated in some drug
      resistant tumor cells. Transfection resulted in increased GCS activity and
      elevated GSH levels (up to 2.6-fold). Cotransfection with the two subunits
      greatly enhanced the synthetic efficiency of the heavy subunit. A direct
      correlation (P < 0.01) between intracellular GSH levels and the LD99 dose of
      melphalan was observed, signifying that elevation of the thiol secondary to GCS
      expression is sufficient to confer the resistance phenotype.

PMID- 7585504
TI  - Rejection antigen peptides on BALB/c RL male 1 leukemia recognized by cytotoxic T
      lymphocytes: derivation from the normally untranslated 5' region of the c-akt
      proto-oncogene activated by long terminal repeat.
AB  - Tumor antigen peptides on BALB/c leukemia RL male 1 that were recognized by
      cytotoxic T lymphocytes were shown to be derived from a normally untranslated
      region of the akt proto-oncogene (Uenaka, A. et al., J. Exp. Med., 180: 1599,
      1994). We show here that the murine leukemia virus (MuLV) long terminal repeat
      (LTR) was inserted directly into the exon of c-akt in RL male 1 leukemia and that
      transcription started from the cap site of the LTR. Translation appeared to start
      from the ATG codon created in the six nucleotides of unknown origin, which were
      inserted into the LTR/akt junction. The deduced molecular size is approximately
      M(r) 59,000 due to the addition of 33 amino acid residues to the normally
      expressed c-AKT protein. Western blot analysis demonstrated the presence of M(r)
      59,000 molecules in an RL male 1 lysate, and their expression at about ten times
      the level of normal AKT molecules of M(r) 56,000, which is consistent with the
      increased expression of akt mRNA demonstrated by Northern blot analysis. The
      findings show that the molecular alteration of AKT protein by insertion of MuLV
      LTR is the mechanism for creating rejection antigen peptides derived from the
      untranslated region of akt.

PMID- 7585505
TI  - The normal cell cycle activation program is exploited during the infection of
      quiescent B lymphocytes by Epstein-Barr virus.
AB  - B lymphocytes in the peripheral circulation are maintained in a non-proliferative
      state. Antigen recognition stimulates limited proliferation, whereas infection
      with Epstein-Barr virus (EBV) results in continual proliferation and the
      outgrowth of immortal cell lines. Because it is not clear at which point in cell
      cycle the peripheral B lymphocytes are arrested, we characterized the expression
      of several cell cycle-associated genes in quiescent and stimulated cells. We show
      that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are
      up-regulated approximately 100-fold as a result of EBV-mediated immortalization.
      Because these genes play a positive role in cell proliferation, we suggest that
      this regulatory switch contributes to controlling entry into the cell cycle.
      Transient stimulation of quiescent B lymphocytes with either a cocktail of anti
      CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four
      genes, suggesting that, after infection, EBV exploits the normal program of B
      lymphocyte cell cycle activation.

PMID- 7585507
TI  - X chromosome inactivation and microsatellite instability in early and advanced
      bilateral ovarian carcinomas.
AB  - Ovarian carcinoma can arise synchronously from multiple independent sites and
      metastasize widely. Therefore, it is frequently unclear whether bilateral tumors
      represent two independent primaries or one primary and a metastasis. We have used
      X chromosome inactivation of the androgen receptor gene and microsatellite
      instability at four chromosomal loci to evaluate the clonal origin of 39
      bilateral ovarian carcinomas. An identical monoclonal pattern was found
      bilaterally in all cases including 10 stage I bilateral ovarian carcinomas.
      Microsatellite alterations were identified in three cases, and in all three,
      identical alterations were present in tumor tissue from both ovaries. These
      results suggest that bilateral ovarian carcinomas evolve as unifocal neoplasias
      and that metastatic dissemination can occur early in the course of the disease.

PMID- 7585508
TI  - Microsatellite instability in colorectal adenocarcinoma cell lines that have full
      length adenomatous polyposis coli protein.
AB  - Almost 20% of colon cancers are characterized by genomic instability at simple
      repeated sequences. This instability is the result of a deficient DNA mismatch
      repair system. Sporadic, as well as hereditary carcinomas of the proximal colon
      display this effect. In this study, we examined colorectal adenocarcinoma cell
      lines, with or without wild-type adenomatous polyposis coli (APC) protein, for
      the presence of microsatellite instability. The three cell lines that maintained
      full-length APC protein also displayed the highest level of instability,
      suggesting a negative correlation between APC mutations and microsatellite
      instability. This data, in addition to other studies that show a negative
      correlation between microsatellite instability and mutations in p53 and K-ras,
      support the idea of a second pathway for colorectal cancer development.

PMID- 7585506
TI  - Expression of thymidine kinase messenger RNA and a related transcript is
      modulated by radioprotector WR1065.
AB  - Previous studies have shown that the radioprotector WR1065 protects against
      mutagenesis across a wide concentration range (i.e., 40 microM to 4 mM) but
      protects against cell killing by ionizing radiation at concentrations greater
      than 1 mM. Other work has demonstrated that many genes are induced or repressed
      after exposure of cells in culture to ionizing radiation, but the actual inducing
      agents for this gene modulation response are unknown. In these experiments, we
      set out to identify genes that would be modulated in response to two different
      concentrations of WR1065 (i.e., a lower dose that is incapable of protecting
      against cell killing but effective in protecting against mutation induction, and
      a high dose that is effective in protecting against both end points). Using
      differential display reverse transcription-PCR, we compared genes expressed in
      untreated cells to those expressed in cells treated with different concentrations
      of WR1065 (4 mM or 40 microM) with or without radiation exposure (7.5 Gy). One
      band, which showed a differential response, was sequenced and found to have
      homology in the 3'-untranslated region of the mouse thymidine kinase (tk) gene
      but not identity to the Chinese hamster ovary tk gene. Dot blot and Northern blot
      analyses confirmed the differential display results and also determined that
      regulation of the tk-like gene is similar to that of tk itself. These experiments
      established that in Chinese hamster ovary cells, radiation causes a repression in
      accumulation of tk mRNA and a related tk-like transcript. This repression is made
      less dramatic by the presence of 40 microM WR1065, and, in fact, expression
      becomes enhanced when cells are pretreated with 4 mM WR1065. This suggests a role
      for regulation of tk and its related gene in the survival response of cells after
      exposure to ionizing radiation.

PMID- 7585509
TI  - Loss of the chromosomal region 10q23-25 in prostate cancer.
AB  - Loss of the chromosomal region 10q23-25 is a frequent event in the progression of
      prostate adenocarcinoma. A candidate tumor suppressor gene from this region, Mxi1
      at 10q25, has recently been shown to be mutated in a small number of prostate
      tumors. To more strictly define those regions of 10q loss that are likely to be
      involved in tumor advancement, we have constructed a detailed deletion map
      spanning 10q23-25 that incorporates Mxi1. Sixty-two % (23 of 37) of tumors
      analyzed exhibited some degree of 10q23-25 loss. Our data suggest the presence of
      a prostate tumor suppressor gene(s) near the 10q23-24 boundary, which was deleted
      in the overwhelming majority (22 of 23) of tumors showing loss. In contrast,
      specific loss of Mxi1, as opposed to loss of other 10q23-25 regions or of the
      entire region, was observed in only 1 of 23 tumors and was accompanied by loss of
      markers at the 10q23-24 boundary. Furthermore, we failed to detect any mutations
      in Mxi1 in those tumors showing Mxi1-associated marker loss by either single
      strand conformation polymorphism analysis or direct DNA sequencing.

PMID- 7585511
TI  - Enzyme/prodrug gene therapy: comparison of cytosine deaminase/5-fluorocytosine
      versus thymidine kinase/ganciclovir enzyme/prodrug systems in a human colorectal
      carcinoma cell line.
AB  - We have been developing an enzyme/prodrug gene therapy approach for the treatment
      of primary and metastatic tumors in the liver. This system uses the cytosine
      deaminase/5-fluorocytosine (CD/5-FCyt) enzyme/prodrug combination. Another system
      that has received considerable attention is the herpes simplex virus thymidine
      kinase/ganciclovir (HSV-TK/GCV) enzyme/prodrug combination. The purpose of the
      present study was to compare these two enzyme/prodrug systems. The human
      colorectal tumor cell line, WiDr, was genetically modified to express either the
      CD gene (WiDr/CD) or the HSV-TK gene (WiDr/TK). The IC50 (concentration of drug
      producing 50% inhibition of cell growth) for GCV was approximately 3.4 microM in
      WiDr/TK cells, while the IC50 for 5-FCyt was approximately 27 microM in WiDr/CD
      cells. In vivo antitumor studies were conducted using high but nontoxic levels of
      GCV (50 mg/kg/day) or 5-FCyt (500 mg/kg/day). When tumor xenografts were composed
      of 100% of cells expressing either HSV-TK or CD, 100% tumor-free animals were
      observed after GCV or 5-FCyt treatment, respectively. However, when only 10% of
      the tumor cells expressed HSV-TK, no antitumor effect by GCV treatment could be
      observed. In contrast, when tumors were composed of 4% of the cells expressing
      CD, 60% of the animals were tumor-free after 5-FCyt treatment. Transmission
      electron microscopy of the WiDr solid tumors revealed the presence of desmosomes
      but no gap junctions.

PMID- 7585512
TI  - Chromosome 5 suppresses tumorigenicity of PC3 prostate cancer cells: correlation
      with re-expression of alpha-catenin and restoration of E-cadherin function.
AB  - Considerable evidence now exists to support an important role for the E-cadherin
      mediated cell-cell adhesion pathway as a suppressor of the invasive phenotype in
      adenocarcinoma cells. Previous studies have found that this pathway is frequently
      aberrant in prostate cancers, particularly those that are likely to metastasize.
      In this study, we report on the effects of re-establishment of this pathway in a
      prostate cancer cell line, PC-3, in which this adhesion system is dysfunctional
      by virtue of a deletion of the gene that codes for alpha-catenin, an E-cadherin
      associated protein necessary for normal E-cadherin function. Re-expression of
      alpha-catenin was accomplished either by transfection of PC-3 cells with a copy
      of the alpha-catenin cDNA under the control of a heterologous promoter or by
      microcell-mediated transfer of chromosome 5, which contains the alpha-catenin
      gene and its normal regulatory elements. In both cases, re-expression of alpha
      catenin is associated with a similar, dramatic alteration in cell morphology,
      whereby extensive cell-cell contact is observed. In the case of transfection of
      the cDNA, this expression is only transient, because the transfected cells either
      cease to proliferate or, more commonly, revert to the parental phenotype with
      concomitant cessation of alpha-catenin expression. In contrast, cells containing
      one or more copies of microcell-transferred chromosome 5 express alpha-catenin in
      a stable manner and continue to proliferate. Upon injection into nude mice, these
      latter cells are no longer tumorigenic, or form only slowly growing tumors with
      greatly extended doubling times when compared to the parental PC-3 cells. During
      passage in culture, clones that contain only one transferred copy of chromosome 5
      reproducibly revert to the parental phenotype. This reversion is associated with
      loss of the chromosome 5 region containing the alpha-catenin gene and consequent
      loss of alpha-catenin expression, as well as re-emergence of tumorigenicity.
      Transfer of chromosome 5 into prostate cancer cells that are E-cadherin negative
      does not result in either morphological transformation or suppression of
      tumorigenicity, suggesting that these effects of alpha-catenin expression are
      dependent upon concomitant expression of E-cadherin. These data demonstrate the
      tumor suppressive ability of chromosome 5 in the PC-3 prostate cancer cells and
      suggest that re-expression of alpha-catenin with resultant restoration of E
      cadherin function plays a critical role in this process.

PMID- 7585510
TI  - Suppression of growth of renal carcinoma cells by the von Hippel-Lindau tumor
      suppressor gene.
AB  - Clear cell renal carcinomas are most frequently characterized by loss of function
      of both copies of the von Hippel-Lindau (VHL) disease gene, suggesting that the
      VHL gene product plays an important role in regulating renal cell proliferation.
      To directly assess the function of the VHL gene product, we transfected the wild
      type VHL gene into two renal carcinoma cell lines that lacked normal expression
      of the gene. Expression of the wild-type VHL gene led to a dramatic suppression
      of growth in two renal carcinoma cell lines, A498 and UMRC6 in vitro, as measured
      by colony formation and direct cell counting. Transfection of a naturally
      occurring mutant VHL gene (nucleotide 713 G to A, Arg to Gln) did not lead to
      growth suppression of these renal carcinoma cells, nor did transfection of the
      wild-type VHL gene into two non-renal tumor cell lines that expressed the
      endogenous wild-type VHL gene. Expression constructs, which included the first
      ATG at nucleotide 214, were sufficient to produce the strongest growth
      suppression. These experiments provide direct evidence that the VHL gene product
      functions to suppress the growth of renal carcinoma cells and also provide a
      model for mapping the domains of the VHL protein important in suppressing tumor
      growth.

PMID- 7585513
TI  - Oncogenic aberrations of p16INK4/CDKN2 and cyclin D1 cooperate to deregulate G1
      control.
AB  - The p16INK4/CDKN2, D-type cyclins, their partner cyclin-dependent kinases, and
      retinoblastoma protein constitute a G1 regulatory pathway commonly targeted in
      oncogenesis. We show that, unexpectedly, abnormalities of p16INK4/CDKN2 occur
      concomitantly in two-thirds of cancer cell lines harboring aberrations of cyclin
      D1. Gene and protein transfer experiments demonstrated that concurrent
      alterations of cyclin D1 and p16 levels cooperate to (de)regulate G1 control in
      diploid fibroblasts, and that both events influence growth of retinoblastoma (RB)
      positive, but not RB-deficient cancer cells. These results show that biological
      consequences of deregulating individual components along the pathway are unequal,
      reflecting their hierarchical roles in the G1 checkpoint control. Whereas RB
      defects eliminate the checkpoint completely, aberrations of the upstream
      components, such as cyclin D1 and p16INK4/CDKN2, can cooperate in multistep
      tumorigenesis.

PMID- 7585514
TI  - Tumor necrosis factor alpha-induced leukocyte adhesion in normal and tumor
      vessels: effect of tumor type, transplantation site, and host strain.
AB  - Tumor necrosis factor alpha (TNF-alpha) can lead to tumor regression when
      injected locally or when used in an isolated limb perfusion, and it can enhance
      the tumoricidal effect of various therapies. TNF-alpha can also up-regulate
      adhesion molecules, and thus, facilitate the binding of leukocytes to normal
      vessels. The present study was designed to investigate the extent to which the
      host leukocytes roll and adhere to vessels of different tumors (MCaIV, a murine
      mammary adenocarcinoma; HGL21, a human malignant astrocytoma) at a given site or
      to the same tumor at different sites (dorsal skin and cranium), in different
      mouse strains [C3H and severe combined immunodeficient (SCID)], both with and
      without TNF-alpha-activation. There was no significant difference in hemodynamic
      parameters such as RBC velocity, diameter, or shear rate between PBS-treated
      control groups and corresponding TNF-alpha-treated groups. Under PBS control
      conditions, the leukocyte rolling count in MCaIV tumor vessels in the dorsal
      chamber in C3H and SCID mice and in the cranial window in C3H mice was
      significantly lower than that in normal vessels (P < 0.05), but stable cell
      adhesion was similar between normal and tumor vessels. TNF-alpha led to an
      increase (P < 0.05) in leukocyte-endothelial interaction in vessels in the
      following cases: normal tissue regardless of sites and strains, MCaIV tumor in
      the cranial window in C3H mice, and HGL21 tumor in the cranial window in SCID
      mice. However, the increase in rolling and adhesion in the MCaIV tumor in
      response to TNF-alpha was significantly lower than in the corresponding normal
      vessels (P < 0.05) in the dorsal chamber in C3H and SCID mice and in the cranial
      window in C3H mice. The HGL21 tumor in the cranial window in SCID mice showed
      leukocyte rolling and adhesion comparable to that in normal pial vessels. These
      findings suggest that (a) in general, basal leukocyte rolling is lower in tumor
      vessels than in normal vessels; (b) leukocyte rolling and adhesion in tumors can
      be enhanced by TNF-alpha-mediated activation; and (c) the TNF-alpha response is
      dependent on tumor type, transplantation site, and host strain. These results
      have significant implications in the gene therapy of cancer using TNF-alpha-gene
      transfected cancer cells or lymphocytes.

PMID- 7585515
TI  - Different tumor types from BRCA2 carriers show wild-type chromosome deletions on
      13q12-q13.
AB  - In this study we examined loss of heterozygosity (LOH) on chromosome 13q12-13 in
      50 tumors from BRCA2 carriers in five families showing strong evidence of linkage
      to BRCA2. In addition to high frequency of LOH in female breast cancer, LOH was
      observed in tumors of the prostate, ovary, cervix, colon, male breast, and
      ureter. All detected losses involved the wild-type chromosome. These results
      suggest that BRCA2 is a tumor suppressor gene and may be involved in the
      tumorigenesis of several cancer types in addition to breast cancer.

PMID- 7585516
TI  - Lack of p16INK4 or retinoblastoma protein (pRb), or amplification-associated
      overexpression of cdk4 is observed in distinct subsets of malignant glial tumors
      and cell lines.
AB  - In this study the expression of p16INK4, retinoblastoma protein (pRb), and cdk4
      proteins have been examined in 18 malignant glioma cell lines and in 45 malignant
      glial tumors. Loss of p16INK4 expression associated with p16INK4 gene homozygous
      deletion was evident in 12 cell lines and in 10 primary tumors. Lack of p16INK4
      expression was also evident in five tumors for which there was no evidence of
      p16INK4 gene homozygous deletion. Two of the cell lines and six of the primary
      tumors in which p16INK4 was present were determined to overexpress cdk4 in
      association with CDK4 gene amplification. Absence of pRb was determined in two of
      the cell lines and in ten of the tumors. In total, 16 of 18 cell lines and 25 of
      45 tumors showed either a lack of p16INK4 or pRb or amplification-associated
      overexpression of cdk4. Two additional tumors showed an absence of pRb and
      p16INK4, and one tumor showed a lack of pRb combined with amplification
      associated overexpression of cdk4. These results suggest a common growth
      regulatory mechanism that is disrupted in gliomas by either suppressing the
      expression of p16INK4 or pRb or by increasing the expression of cdk4.

PMID- 7585517
TI  - Riboflavin-mediated photosensitization of Vinca alkaloids distorts drug
      sensitivity assays.
AB  - Poor reproducibility of cytotoxicity tests with Vinca alkaloids has frequently
      been reported. A commonly presumed light sensitivity of the drugs could not be
      confirmed. However, we found that they are photosensitized by riboflavin (vitamin
      B2), an obligatory component of cell culture media. Light of wavelengths below
      500 nm triggered rapid photoreactions of riboflavin with vinblastine,
      vincristine, and vindesine in aqueous solutions. The photoreactions altered the
      absorption spectra of these alkaloids and yielded degradation products that could
      be separated by TLC. In cell cultures, both immediate and persisting, riboflavin
      mediated photoreactivity could be distinguished. They preclude reliable
      determinations of sensitivity and resistance to Vinca alkaloids, as exemplified
      on chemosensitive and multidrug-resistant mouse ascites cells. In experiments
      involving photosensitization, the 50% inhibitory concentration values of
      sensitive and resistant cells were overlapping and fluctuated in the ranges from
      3 to 30 nM and 15 to 360 nM vinblastine, respectively. Corresponding values from
      series of experiments protected from photosensitization were 1.02 +/- 0.22 nM and
      18.5 +/- 3.42 nM. Hence, riboflavin-mediated photoreactions must be fully
      prevented in assays of cellular drug sensitivity. Procedures for eliminating
      immediate as well as persisting photoreactivity were established.

PMID- 7585519
TI  - The H-ras oncogene interferes with retinoic acid signaling and metabolism in
      NIH3T3 cells.
AB  - We have previously shown that retinoic acid (RA) fails to induce transglutaminase
      C in H-ras transformed NIH-3T3 cells. Therefore, we investigated the effect of
      the H-ras oncogene on the metabolism of RA and on the expression of the cellular
      RA-binding protein I mRNA. HPLC analysis of the media and cell extracts
      demonstrated that H-ras-transformed cells metabolize RA to a much lesser extent
      than control cells, resulting in a higher concentration of RA in H-ras cells.
      Although inactive in endogenous transglutaminase induction, H-ras cell-associated
      RA was shown to be biologically available to induce activation of a reporter
      construct containing a retinoid response element and in stimulating
      transglutaminase activity in nontransfected cells. Cellular RA-binding protein I
      mRNA, supposedly involved in RA storage, was significantly increased in the H-ras
      transformed cells. These data demonstrate that, even though H-ras-transformed
      cells accumulate up to 20 fold the concentration of RA as NIH-3T3 cells, they
      fail to show transglutaminase induction, suggesting that H-ras interferes with
      signal transduction by RA.

PMID- 7585518
TI  - ET-18-OCH3 inhibits nuclear factor-kappa B activation by 12-O
      tetradecanoylphorbol-13-acetate but not by tumor necrosis factor-alpha or
      interleukin 1 alpha.
AB  - 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is a synthetic
      diether phospholipid that is competitive with phosphatidylserine binding to the
      regulatory domain of protein kinase C (PKC). Our previous studies indicate that
      the selective inhibition of tumor cell growth by ET-18-OCH3 may be due to altered
      signal transduction mechanisms, including the inhibition of PKC. To further
      define the mechanism of action of ET-18-OCH3, we have used it to study the role
      of PKC in regulation of the transcription factor NF-kappa B, which is activated
      by diverse stimuli. In the 293.27.2 human kidney cell line, as in hematopoietic
      cells of all lineages, NF-kappa B is stimulated by 12-O-tetradecanoylphorbol-13
      acetate (TPA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha
      (IL-1 alpha). The response to either TNF-alpha or IL-1 alpha is synergistically
      enhanced by TPA. However, the regulatory mechanisms and signal transduction
      systems responsible for NF-kappa B activation in response to these different
      stimuli have not been determined in detail. We have used ET-18-OCH3 and
      auranofin, which inhibit PKC by different mechanisms, to assess the role of PKC
      in NF-kappa B activation. ET-18-OCH3 markedly inhibits TPA-induced NF-kappa B
      activation, as measured by HIV long terminal repeat-directed expression of beta
      galactosidase. The IC50 for inhibition by ET-18-OCH3 is approximately 2 microM, a
      noncytotoxic concentration. Inhibition of TPA-induced NF-kappa B activation was
      dependent upon preincubation with ET-18-OCH3, and the drug was active at
      approximately 2 mol% of total cellular phospholipid. ET-18-OCH3 did not inhibit
      NF-kappa B activation by either TNF-alpha or IL-1 alpha, indicating that there
      are multiple distinct signal transduction pathways leading to activation of NF
      kappa B. We have confirmed these results using auranofin, an antirheumatic drug
      that is a specific PKC inhibitor interacting with the catalytic domain. Like ET
      18-OCH3, auranofin blocked NF-kappa B activation by TPA but not by TNF-alpha or
      IL-1 alpha. Also like the ether lipid, auranofin only partially blocked the
      synergy exhibited by TPA and TNF-alpha. To confirm the role of NF-kappa B in this
      response, we measured NF-kappa B by electrophoretic mobility shift assay. Both ET
      18-OCH3 and auranofin inhibited cellular induction of the active NF-kappa B
      complex in response to TPA but not in response to TNF-alpha.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7585521
TI  - Cholesterol sulfate, a second messenger for the eta isoform of protein kinase C,
      inhibits promotional phase in mouse skin carcinogenesis.
AB  - Cholesterol sulfate is a second messenger for the eta isoform of protein kinase C
      mediating squamous differentiation. We found that cholesterol sulfate inhibited
      the promotional phase of skin carcinogenesis in female CD-1 mice, which was
      initiated by 100 micrograms 7,12-dimethylbenz[a]-anthracene and promoted by a
      single application of 10 micrograms 12-O-tetradecanoylphorbol-13-acetate,
      followed by repeated applications of 10 micrograms mezerein once a week for 19
      weeks. Cholesterol sulfate, when applied topically at a dose of 400 micrograms
      (820 mumol) 10 min before treatment with the promoters, markedly suppressed tumor
      formation, resulting in decrease of 56% in the incidence of tumor-bearing mice,
      81% in the number of tumors/mouse, and 60% in the size of tumors at 20 weeks of
      the promotion. This inhibition was not due to elimination of the initiated cells.
      Treatment with the parental cholesterol at a dose of 320 micrograms (820 mumol),
      which does not activate the eta isoform, did not inhibit tumor promotion.
      Repeated treatment with cholesterol sulfate induced scaling of skin at the site
      of application. Cholesterol sulfate, unlike most inhibitors of tumor promotion,
      did not inhibit induction of ornithine decarboxylase and hyperplasia in mouse
      epidermis caused by topical treatment with 12-O-tetradecanoylphorbol-13-acetate.
      These findings suggest that cholesterol sulfate inhibits tumor promotion by
      stimulating a differentiation pathway mediated by the eta isoform of protein
      kinase C.

PMID- 7585520
TI  - Characterization of the receptor protein tyrosine phosphatase gene product PTP
      gamma: binding and activation by triphosphorylated nucleosides.
AB  - A full-length cDNA for a novel isoform of the human receptor tyrosine phosphatase
      gamma gene (PTPRG) was overexpressed in Sf9 insect cells, and the gene product,
      PTP gamma, was purified and characterized. The protein was expressed as a M(r)
      approximately 185,000 protein accompanied by a M(r) approximately 120,000
      putative cleavage product on SDS-PAGE analysis. The protein undergoes N-linked
      glycosylation and constitutive phosphorylation of serine residues. When assayed
      for tyrosine-specific phosphatase activity, PTP gamma dephosphorylated myelin
      basic protein at a pH optimum of 7.5 and a Km of 12.6 microM; reduced
      carboxyamidomethylated and maleylated lysozyme (RCM-lysozyme) at a pH optimum of
      6.0 and a Km of 12 microM; and p-nitrophenylphosphate with a pH optimum of 5.5
      and a Km of 3.5 mM. Phosphatase activity was inhibited by ZnCl2 and sodium
      orthovanadate; Mg2+, Mn2+, and Ca2+ ions were ineffective. The partially purified
      form of the enzyme was allosterically activated by triphosphorylated nucleosides,
      with a preference for purines. This activation was prevented by Mg2+ addition and
      did not occur when a purified form of the enzyme was utilized, suggesting that
      its activation depends on specific activating factors or conformational
      constraints. Interestingly, PTP gamma protein was specifically bound by an ATP
      agarose matrix through its intracellular domain, suggesting a link between
      binding of nucleotides and activation of the phosphatase.

PMID- 7585522
TI  - Chemoprevention by dehydroepiandrosterone and indomethacin in a rat multiorgan
      carcinogenesis model.
AB  - The chemopreventive efficacy of dehydroepiandrosterone (DHEA) and indomethacin
      (IM) alone or in combination was investigated in a rat multiorgan carcinogenesis
      model. These two chemicals were selected as chemopreventive agents with different
      functions. Animals were sequentially given five carcinogens with different organ
      target sites in the first 4-week initiation period. One week after its
      completion, the rats received 0.3% DHEA in the diet, 20 ppm IM in the drinking
      water, or 0.3% DHEA + 20 ppm IM until experimental week 28. DHEA enhanced
      hepatocarcinogenesis, but concurrent treatment with IM suppressed tumor
      development as compared to the DHEA group. DHEA inhibited tumor development in
      the thyroid, with a similar tendency observed for the small intestine. In
      addition, treatment with this hormone decreased occurrences of preneoplasias in
      the urinary bladder and seminal vesicles. Treatment with IM clearly suppressed
      development of preneoplasias or neoplasias in the lung and small and large
      intestines. In the urinary bladder, treatment with IM tended to decrease
      preneoplastic lesion development. Analysis of multiplicity of total tumors of any
      category revealed comparable values for DHEA and control groups, while the IM
      group showed a significant reduction. IM in combination with DHEA caused
      suppression as compared to DHEA alone. In a separate 8-week experiment, DHEA or
      IM were administered for 4 weeks after prior carcinogen application, and
      biochemical responses in the target organs were investigated. DHEA increased
      glucose-6-phosphate dehydrogenase levels in the liver but caused a decrease in
      the small intestine. In addition, DHEA decreased serum T4 but not T3. IM
      decreased prostaglandin E2 content in the small intestine. In conclusion,
      although DHEA or IM exert significant chemopreventive effects in multiorgans with
      the exception of the DHEA-treated liver case, treatment in combination did not
      result in amplification of their beneficial influence. Our results suggest the
      possible application of IM for chemoprevention in high-risk individuals, but the
      question of effects of DHEA in the liver must be answered before this hormone can
      be considered for use in humans.

PMID- 7585524
TI  - Tumor necrosis factor and coagulopathy in patients with prostate cancer.
AB  - This study was undertaken to evaluate the relationship between serum tumor
      necrosis factor (TNF) and coagulopathy in patients with prostate cancer. TNF
      levels in 104 sera obtained from 101 prostate cancer patients were determined
      using an enzyme immunoassay. Serum levels of fibrin/fibrinogen degradation
      product E fragment (FDP) and plasma levels of fibrin degradation product D-dimer
      in patients with elevated serum TNF levels were 1221.95 +/- 375.94 ng/ml and
      27.34 +/- 9.81 micrograms/ml, which were significantly higher than those (FDP,
      94.35 +/- 13.17 ng/ml; D-dimer, 1.03 +/- 0.20 micrograms/ml) in patients with
      undetectable serum TNF levels (P < 0.01). In addition, patients with elevated
      serum TNF levels showed significant increases in plasma levels of thrombin
      antithrombin-III complex and plasmin-alpha 2-antiplasmin inhibitor complex and a
      significantly higher incidence of positive plasma soluble fibrin monomer complex
      than did those with undetectable serum TNF levels. The percentage of prothrombin
      time was significantly decreased in the group with elevated serum levels of TNF.
      Serum levels of TNF were significantly elevated in patients with serum FDP levels
      of > or = 200 ng/ml than in those with serum FDP levels of < 200 ng/ml (3.91 +/-
      0.45 versus 2.17 +/- 0.08 units/ml) and in patients with plasma D-dimer levels of
      > or = 2 micrograms/ml than in those with plasma D-dimer levels of < 2
      micrograms/ml (3.82 +/- 0.48 versus 2.10 +/- 0.06 units/ml). These results
      suggest that TNF may be one of the pathogenetic factors that could explain the
      occurrence of coagulopathy in patients with prostate cancer.

PMID- 7585523
TI  - Promotion of N-nitrosodiethylamine-initiated hepatocellular tumors and
      hepatoblastomas by 2,3,7,8-tetrachlorodibenzo-p-dioxin or Aroclor 1254 in
      C57BL/6, DBA/2, and B6D2F1 mice.
AB  - To investigate the hypothesis that tumor promotion by chlorinated aromatic
      hydrocarbons involves Ah receptor occupation and subsequent induction of
      cytochromes P-450 1a-1, effects of Aroclor 1254 or 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) were examined in N-nitrosodiethylamine-initiated mice with
      different Ah receptor phenotype. Levels of cytochromes P-450 1a and 2b were
      measured by enzyme assay and Western immunoblots. Males of the C57BL/6, DBA/2, or
      (C57BL/6 x DBA/2)F1 (hereafter referred to as "B6D2F1") strain were initiated
      with a single i.p. dose of N-nitrosodiethylamine (90 mg/kg body weight), followed
      by either multiple doses of TCDD (0.05 micrograms/kg) weekly or Aroclor 1254
      chronically in the diet (100 ppm) for 20 weeks, and then no treatment for 24
      weeks. Lung tumor incidence or multiplicity was not altered by either of the
      promoters. Liver tumor incidence was similar among the three strains after N
      nitrosodiethylamine alone (14, 21, and 21%, respectively). In DBA/2 mice, TCDD
      neither induced Cyp 1a nor promoted liver tumors. Aroclor caused an 8-fold
      induction of hepatic Cyp 2b, which was its maximum at the 12-week time point but
      did not promote tumors. Inductions of hepatic Cyp 1a by TCDD and 1a and 2b by
      Aroclor were similar in C57BL/6 and B6D2F1 mice, but tumor promotion responses
      were quite different. Dietary Aroclor significantly promoted liver tumors in
      C57BL/6 mice (59 versus 14%) but not in B6D2F1 mice (24 versus 21%). Repeated
      TCDD promoted only in B6D2F1 mice (52 versus 21%) and not in C57BL/6 mice (19
      versus 14%). Thus, whereas these data confirm that a functional Ah receptor is
      required for liver tumor promotion, the degree of activation as measured by
      induction of Cyp 1a is not directly related to the degree of tumor-promoting
      capability. Other genetic factors must play a role in mediating the final tumor
      outcome.

PMID- 7585526
TI  - Reduction in the expression and action of transforming growth factor beta 1 on
      lactotropes during estrogen-induced tumorigenesis in the anterior pituitary.
AB  - We have previously shown that transforming growth factor beta 1 (TGF-beta 1)
      receptor and TGF-beta type II receptor (T beta R-II) are produced in lactotropes,
      and that TGF-beta 1 inhibits the growth of these anterior pituitary cells by an
      autocrine mechanism. To study the changes of the expression and function of this
      growth factor during tumorigenesis, we have measured the levels of TGF-beta 1 and
      T beta R-II mRNAs and proteins in the normal and tumor anterior pituitary cells
      in vivo and in vitro and have compared the cell growth responses to TGF-beta 1 in
      normal and tumor pituitary cells in vitro. Treatment with estradiol-17 beta for
      1, 2, 4, and 8 weeks caused a time-dependent increase in pituitary protein,
      prolactin, and prolactin mRNA levels and in plasma prolactin levels, suggesting
      that estrogen enhanced lactotropic proliferation in anterior pituitary glands.
      The levels of TGF-beta 1 protein and mRNA in anterior pituitary tissues were
      reduced over time after estrogen treatment during the development of pituitary
      tumors. The mRNA and protein levels of T beta R-II decreased markedly during the
      development of pituitary tumors. In addition, two transformed lactotropes, GH3
      and PR1 cell lines, showed markedly reduced levels of TGF-beta 1 as well as T
      beta R-II mRNA. Comparison of the antiproliferative effects of TGF-beta in
      transformed and normal lactotropes in cultures revealed that the sensitivity of
      GH3 cells is reduced, and that PR1 cells are virtually resistant to TGF-beta
      1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585525
TI  - Pituitary adenylate cyclase activating peptide receptors regulate the growth of
      non-small cell lung cancer cells.
AB  - We have identified pituitary adenylate cyclase activating peptide (PACAP)
      receptors on small cell lung cancer cell line NCI-N417 in a previous study. In
      this study, the role of PACAP in the growth and signal transduction of non-small
      cell lung cancer cells was investigated. Northern blot analysis with a full
      length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing
      transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound
      with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 14,000/cell)
      when NCI-H838 cells were used. Specific 125I-labeled PACAP binding was inhibited
      with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6
      38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38),
      and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the
      increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not
      vasoactive intestinal polypeptide, elevated cytosolic Ca2+ in individual NCI-H838
      cells. PACAP-27 stimulated arachidonic acid release, and the increase caused by
      PACAP was reversed by PACAP(6-38). PACAP-27 stimulated colony formation in NCI
      H838 cells, whereas the PACAP antagonist PACAP(6-38) reduced colony formation in
      the absence or presence of exogenous PACAP-27. In nude mice bearing NCI-H838
      xenografts, PACAP(6-38) slowed tumor growth significantly. These data suggest
      that biologically active type 1 PACAP receptors are present on human non-small
      cell lung cancer cells, which exhibit dual signal transduction pathways and
      regulate cell proliferation.

PMID- 7585528
TI  - Cigarette smoking in relation to risk of large bowel cancer in women.
AB  - Smoking habits were ascertained by interview from Wisconsin women aged 30-74
      years with newly reported diagnoses of colon (n = 536) and rectal (n = 243)
      cancer and 2315 randomly selected population controls. After controlling for age,
      body mass index, alcohol consumption, family history of large bowel cancer, and
      history of screening sigmoidoscopy, significantly elevated risks were observed
      for women who had ever smoked, in both the colon (odds ratio, 1.28; 95%
      confidence interval, 1.03-1.58) and rectum (odds ratio, 1.44; 95% confidence
      interval, 1.08-1.92). Risk significantly increased with greater number of
      cigarettes smoked per day, longer duration of smoking, and earlier age at
      initiation for both the colon and the rectum; however, only duration of smoking
      was not independently associated with risk. Among former smokers, risk for both
      colon and rectal cancer remained elevated. These data suggest that women who
      smoke are at elevated risk of both colon and rectal cancer and that increased
      risk persists even among former smokers.

PMID- 7585527
TI  - Alcohol and pancreatic cancer in blacks and whites in the United States.
AB  - A population-based, case-control study of pancreatic cancer based on direct
      interviews with 307 white and 179 black incident cases and 1164 white and 945
      black population controls was conducted in three areas of the United States to
      determine the role alcohol drinking plays as a risk factor for pancreatic cancer
      and to estimate the extent to which it may explain the higher incidence of
      pancreatic cancer in blacks compared to whites. Our findings indicate that
      alcohol drinking at the levels typically consumed by the general population of
      the United States is probably not a risk factor for pancreatic cancer. Our data
      suggest, however, that heavy alcohol drinking may be related to pancreatic cancer
      risk. Among men, blacks and white who drank at least 57 drinks/week had odds
      ratios (ORs) of 2.2 [95% confidence interval (CI) = 0.9-5.6] and 1.4 (95% CI =
      0.6-3.2), respectively. Among women, blacks who drank 8 to < 21 drinks/week had
      an OR of 1.8 (95% CI = 0.8-4.0), and those who drank at least 21 drinks/week had
      an OR of 2.5 (95% CI = 1.02-5.9), but whites with the same levels of alcohol
      intake experienced no increased risk. Compared to whites, blacks had
      significantly higher ORs associated with heavy alcohol drinking (> or = 57
      drinks/week) in men (P = 0.04) and with moderate-to-heavy drinking (> or = 8
      drinks/week) in women (P = 0.03). Additional research is needed to determine
      whether heavy alcohol drinking is causally related to pancreatic cancer and
      whether the risk of alcohol-related pancreatic cancer is greater in blacks than
      in whites.

PMID- 7585530
TI  - A radioresistant variant derived from a human neuroblastoma cell line is less
      prone to radiation-induced apoptosis.
AB  - By subjecting radiosensitive human neuroblastoma IMR 32 cells to a regime of
      fractionated X-irradiation, a radioresistant variant, XRIMR 32, was obtained.
      Radiation resistance of XRIMR 32 cells was demonstrated by clonogenic and
      spheroid regrowth delay assays. The XRIMR 32 cultures were phenotypically
      unstable, with the resistant phenotype being lost after 3 passages in the absence
      of radiation-selective pressure, but a monoclonal cell line (clone F) was
      established that maintained its resistance over 35 passages without irradiation.
      Flow cytometry showed that exponentially growing IMR 32, XRIMR 32, and clone F
      cells all had very similar cell cycle distributions. Studies of initial DNA
      damage and repair, using the technique of neutral filter elution, revealed no
      differences between these lines. Chromosomal damage, as measured by micronucleus
      frequency following irradiation, was also seen to be very similar. However,
      studies of apoptosis following irradiation showed significantly higher levels of
      apoptosis in IMR 32 cells, compared to the resistant lines. This was true at all
      time points studied between 6 and 42 h after irradiation. p53 status was examined
      in the IMR 32 and clone F cells. No mutations were detected in exons 5-8 of the
      cDNA. Both lines showed increased p53 expression after irradiation. These data
      are consistent with the evolution of cellular resistance as a possible mechanism
      for the evolution of cellular radioresistance during protracted radiation
      regimes. However, the molecular mechanism responsible for the increased
      radioresistance remains to be discovered.

PMID- 7585529
TI  - Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen
      induced damage in human lung.
AB  - The formation of carcinogen-DNA adducts within the respiratory epithelium is
      thought to be a critical factor in the induction of lung cancer from tobacco
      smoke. A reliable surrogate measure of carcinogen damage to the lung would be of
      great value in molecular epidemiological studies of cancer risk. The validity of
      measurements of DNA adducts formed from hydrophobic aromatic hydrocarbons in
      peripheral blood mononuclear cells (MNCs) was investigated by comparing the
      levels of aromatic DNA adducts detected in lung tissue from 31 lung cancer
      patients with those detected in MNCs from the same individuals using the 32P
      postlabeling assay. The associations of smoking history and intake of dietary
      antioxidants with adduct levels also were assessed. Tissue-specific, as well as
      common DNA adducts were detected in lung and blood; total MNC adduct levels were
      highly correlated with total lung adducts. After smoking cessation, adduct levels
      appeared to decay in both tissues at similar rates. Multivariate analyses
      (Poisson regression modeling) indicated that dietary antioxidant intake
      (carotenoids, vitamin A, and retinol) modified the levels of aromatic DNA adducts
      in both the lungs and blood. Of all models tested, the optimal one for predicting
      lung adduct levels included the measure of blood MNC adduct levels only.
      Therefore, blood MNCs are a valid surrogate tissue for estimating the burden of
      DNA adducts in respiratory tissue in molecular epidemiological studies.

PMID- 7585533
TI  - Efficacy of Acylfulvene Illudin analogues against a metastatic lung carcinoma
      MV522 xenograft nonresponsive to traditional anticancer agents: retention of
      activity against various mdr phenotypes and unusual cytotoxicity against ERCC2
      and ERCC3 DNA helicase-deficient cells.
AB  - Four second-generation Illudin analogues were synthesized and tested for
      antitumor activity using a metastatic lung carcinoma xenograft model resistant to
      conventional antitumor agents. One analogue, the parent illudofulvene-derivative
      called Acylfulvene, inhibited xenograft primary tumor growth and prolonged life
      span of tumor-bearing animals when administered i.p. or i.v. The efficacy of
      Acylfulvene exceeded that of mitomycin C, cisplatin, paclitaxol, the parent
      compound Illudin S, and an earlier analogue, dehydroilludin M. Promising features
      of this new analogue are: (a) the retention of in vitro activity against a
      variety of mdr tumor phenotypes including gp170+, gp150+, GSHTR-Pi, topoisomerase
      I, and topoisomerase II mutants; and (b) an apparent selective cytotoxicity
      toward cells deficient in either ERCC2 or ERCC3 DNA helicase activity.

PMID- 7585531
TI  - BCL-2 expression delays drug-induced apoptosis but does not increase clonogenic
      survival after drug treatment in HeLa cells.
AB  - Apoptosis is a major form of cell death induced by chemotherapeutic drugs.
      Overexpression of the proto-oncogene bcl-2 can prevent apoptosis in various types
      of cells. We have constructed a HeLa S3 cell line in which the expression of bcl
      2 can be controlled by the concentration of tetracycline in the medium. Using
      this system, we show that apoptosis induced by various cytostatic treatments
      could be delayed by the overexpression of bcl-2, as assayed by vital dye
      exclusion, apoptotic nuclei morphology, DNA histogram shift, and DNA
      fragmentation. Quantitative analysis revealed a hyperbolic curve when protection
      from apoptosis was plotted against the amount of Bcl-2. When cells were treated
      with aphidicolin for 12, 24, or 36 h and then replated in fresh media to assay
      for colony formation, the majority of cells that did not show apoptotic
      morphology at the time of drug removal failed to form colonies. Furthermore, Bcl
      2 did not increase colony formation after 12-36 h of aphidicolin treatment.
      Therefore, with aphidicolin treatment, cells were committed to the death program
      upstream of the point of Bcl-2 action.

PMID- 7585532
TI  - Attenuation of interleukin 2-induced pulmonary vascular leak syndrome by low
      doses of oral methotrexate.
AB  - Pulmonary vascular leak induced in mice by interleukin 2 (IL-2) was attenuated by
      pretreatment with single or multiple doses of oral methotrexate. Methotrexate
      also attenuated pulmonary vascular leak when either larger doses of IL-2 or when
      lymphokine-activated killer (LAK) cells or LAK cells plus IL-2 were administered.
      Lymphoid infiltrates in the lungs of mice treated with IL-2 and methotrexate were
      significantly lower. The number of mice surviving treatment with high doses of IL
      2 was also significantly increased when these mice were treated with
      methotrexate. Methotrexate prevented the IL-2-induced increase in the number of
      splenocytes that were asialo GM1+ but had no effect on Lyt 2+ or L3T4+ cell
      content. A marginal but significant inhibition in the generation of effector
      splenocytes that were cytolytic to either YAC or MCA-205 tumor targets was
      observed in mice treated with methotrexate and IL-2. In vivo studies indicated
      that methotrexate did not compromise the anti-tumor efficacy of treatment
      regimens that contained IL-2, LAK cells, or IL-2 and LAK cells. These results
      demonstrate the potential clinical utility of methotrexate in attenuating
      pulmonary vascular leak induced by IL-2 without compromising its efficacy. One
      potential mechanism of action of methotrexate is related to its ability to
      stimulate the release of adenosine followed by the inhibition of the adhesion of
      leukocytes to the IL-2-activated endothelium.

PMID- 7585534
TI  - Combined vaccination with major histocompatibility class I and interleukin 2 gene
      transduced melanoma cells synergizes the cure of postsurgical established lung
      metastases.
AB  - We have analyzed and compared in detail the malignant phenotypes of, the immune
      mechanisms induced by, and the immunotherapeutic potentials of B16-F10.9 melanoma
      cells manipulated by gene transfer to express syngeneic H-2Kb molecules or to
      secrete the cytokines interleukin 2 (IL-2) or IL-6. Local tumor growth in the
      footpad of transduced cells is mainly retarded by expression of H-2Kb and IL-2
      genes and less by expression of IL-6. Mice given injections intrafootpad of
      tumorigenic doses of transduced clones manifested significantly reduced
      postsurgical spontaneous metastasis. After i.v. inoculation, mice given
      injections of F10.9-Kb expressors did not develop experimental lung metastases;
      mice given injections of F10.9-IL-6 secretors developed reduced metastatic loads;
      whereas mice given injections of F10.9-IL-2 secretors developed high loads of
      lung metastases. On the basis of injections into nude mice, in vivo depletions of
      CD4+, CD8+, and NK1.1+ cells, and in vitro CTL and natural killer (NK) assays, we
      show that all F10.9-modified cells induce CD8+ tumor-specific CTL activity and
      that F10.9-IL-2 secretors also induce nonspecific NK/lymphokine-activated killer
      cell activity. Vaccinations with F10.9-modified cells were capable of
      significantly reducing metastatic spread from small established F10.9 footpad
      tumors. However, in mice carrying preestablished lung metastases, a highly
      therapeutic effect was achieved only when H-2Kb expressors and IL-2 secretors
      were combined in vaccination, whereas individual vaccines or other combinations
      had marginal effects. This higher efficiency of the combined vaccine is due to
      the combined effect of efficient CTL induction and NK/lymphokine-activated killer
      cell activity as concluded from depletion of CD8+ and NK1.1 cells during
      immunotherapy. Thus, the cure of established metastasis can be achieved by the
      synergistic effects of vaccination with class I and IL-2-transduced tumor cells.

PMID- 7585535
TI  - The erbstatin analogue methyl 2,5-dihydroxycinnamate cross-links proteins and is
      cytotoxic to normal and neoplastic epithelial cells by a mechanism independent of
      tyrosine kinase inhibition.
AB  - Differentiation therapy is an attractive option for the treatment of superficial,
      localized neoplastic lesions of the skin. Topical application of agents that
      induce differentiation could selectively inhibit tumor cell growth, inducing a
      program of cell death with the production of cross-linked protein envelopes as
      the terminal event of this process at the skin surface, effectively eliminating
      the neoplastic phenotype. The nonspecific kinase inhibitor staurosporine induces
      cornified envelope assembly in neoplastic keratinocytes and causes tumor
      regression (A. A. Dlugosz and S. H. Yuspa, Cancer Res., 51: 4677-4684, 1991). In
      pursuit of less toxic agents, specific tyrosine kinase inhibitors were tested for
      the ability to induce differentiation in keratinocyte-derived cells. Of a range
      of inhibitors tested, only MC was able to induce cross-linked protein and
      consequent cell death in mouse and human primary normal keratinocytes, 308
      neoplastic mouse keratinocytes, HPV-18-infected immortalized human keratinocytes,
      and human lines SQCC-Y1 (squamous carcinoma) and A431 (epidermoid carcinoma). MC
      increased cross-linked protein in a dose-dependent manner (0.05-1 mM). To confirm
      differentiation, MC-treated mouse primary normal keratinocytes were tested for
      activation of the endogenous cross-linking enzyme transglutaminase, but no
      association was found between transglutaminase activity and MC-induced protein
      cross-linking. MC also induced protein cross-linking in the fibroblast cell line
      NIH3T3 and in B16 melanoma cells, in which cornified envelope assembly is not
      part of the differentiation process. This cross-linking occurred at 4 degrees C,
      suggesting a nonphysiological process. Western blot analysis of an in vitro assay
      with purified EGF receptor showed that MC was able to cross-link the receptor. As
      in NIH3T3 cells, DTT inhibited cross-linking, suggesting that oxidation of MC or
      an acceptor group may be required for this effect. Thus, MC does not induce
      differentiation by a physiological mechanism in epithelial cells but causes
      chemical protein cross-linking into cornified envelope-like structures at high
      concentration.

PMID- 7585536
TI  - Antiproliferative and angiostatic activity of suramin analogues.
AB  - Suramin, a polyanionic naphthylurea, represents a novel class of antineoplastic
      drugs with a variety of activities against tumor cell proliferation. However, its
      clinical use is hampered by serious toxicity. To gain more insight into structure
      activity relationships of suramin, we investigated the antiproliferative action
      of suramin and 19 suramin analogues in vitro using 5 different human cell lines
      (HT29, MCF7, SW13, PC3, and T47D). In addition, for seven analogues the
      angiostatic potential with and without hydrocortisone was assessed using a
      modified chorioallantois membrane assay. Only the symmetric compounds exhibited
      antiproliferative action in vitro; several analogues were more active than
      suramin (e.g., NF031, NF037, NF326). Suramin analogues with six sulfonic acid
      groups showed a wide range of activity in HT29 cells (IC50 = 43-390 microM),
      indicating that besides the polyanionic feature, other structural elements are
      important (e.g., stiffness of the bridge between the two terminal naphthyl
      rings). Some of the smaller ureas with only four sulfonic acid groups retained
      significant antiproliferative activity. Compounds active in cell lines also
      inhibited angiogenesis in the chorioallantois membrane assay, suggesting a
      similar mode of action. Hydrocortisone increased the angiostatic effect of most
      but not all of the screened suramin analogues. These findings may guide the use
      of suramin analogues for improved antitumor therapy in vivo.

PMID- 7585537
TI  - Selective use of an alternative stop codon and polyadenylation signal within
      intron sequences leads to a truncated topoisomerase II alpha messenger RNA and
      protein in human HL-60 leukemia cells selected for resistance to mitoxantrone.
AB  - Topoisomerase II alpha is an essential nuclear enzyme involved in DNA replication
      and a target for many of the clinically useful antineoplastic agents. In a
      mitoxantrone-selected human leukemia cell line, HL-60/MX2, cellular topoisomerase
      II (topo II) catalytic activity is decreased, in association with the finding of
      reduced nuclear topo II alpha and beta protein levels. In addition, HL-60/MX2
      cells contain a novel M(r) 160,000 topo II alpha-related protein that localizes
      predominantly to the cell cytoplasm (W. G. Harker et al., Biochemistry, 30: 9953
      9961, 1991). In these studies, we have investigated the molecular mechanisms
      underlying the altered expression of the topo II alpha protein(s) in these cells.
      Three topo II alpha mRNAs, 7.2, 6.3, and 4.8 kb, were identified in the HL-60/MX2
      cells, with the 6.3 and 4.8 kb transcripts being present in roughly equivalent
      amounts, while the 7.2-kb mRNA represents < 7% of the total topo II alpha
      specific mRNA. Portions of the 3'-coding and 3'-untranslated regions were found
      to be missing from the 7.2- and 4.8-kb topo II alpha mRNAs by Northern blot
      analysis. Sequences encoding the 3' regions of the normal and truncated forms of
      the topo II alpha enzyme were obtained from the HL-60/MX2 cells through the use
      of a 3'-rapid amplification of cDNA ends strategy. Approximately 1321 nucleotides
      are missing from the 3'-coding and 3'-untranslated regions of the 4.8-kb mRNA and
      are replaced by 122 nucleotides that contain an in-frame stop codon and consensus
      polyadenylation signal. The translation product of the truncated 4388-bp topo II
      alpha transcript would have a predicted M(r) of 157,850, with 108 COOH-terminal
      amino acids being replaced by 13 novel residues. Immunoblot analysis confirmed
      that amino acids in the COOH-terminal region of topo II alpha were missing from
      the M(r) 160,000 HL-60/MX2 protein, and antisera generated to a synthetic peptide
      representing the 13 unique amino acids identified a M(r) 160,000 protein in
      nuclear extracts from these cells. PCR evaluation of the organization of the 3'
      region of the topo II alpha gene revealed that the 4.8-kb mRNA found in HL-60/MX2
      cells diverges from that of the 6.3-kb mRNA at a consensus exon-intron splice
      donor site. The 122-bp novel nucleotides identified in the truncated transcript
      appear to originate from an adjacent intron as a result of altered RNA
      processing. These studies suggest that as a result of the disruption of the
      carboxy terminus of the topo II alpha protein and the putative nuclear targeting
      sequences identified therein, cellular localization of the protein is altered,
      which may confer a growth advantage for the HL-60/MX2 cells in the presence of
      mitoxantrone.

PMID- 7585538
TI  - Recognition of multiple epitopes in the human melanoma antigen gp100 by
      peripheral blood lymphocytes stimulated in vitro with synthetic peptides.
AB  - gp100 is a melanocyte lineage-specific antigen recognized by tumor-infiltrating
      lymphocytes whose adoptive transfer has been associated with tumor regression in
      patients with metastatic melanoma. The peripheral blood mononuclear cells of five
      melanoma patients were sensitized in vitro with synthetic peptides to elicit
      antigen-specific cytotoxic T lymphocyte (CTL) lines against four gp100 epitopes.
      These epitope-specific CTL lines were generated following weekly in vitro
      stimulation with the synthetic decamer G10(476) (V-L-Y-R-Y-G-S-F-S-V) or the
      nonamers G9(280) (Y-L-E-P-G-P-V-T-A), G9(154) (K-T-W-G-Q-Y-W-Q-V), or G9(209) (I
      T-D-Q-V-P-F-S-V) pulsed onto autologous irradiated peripheral blood mononuclear
      cells. These lines grew as long as 4 months in culture in low-dose interleukin 2
      (30 IU/ml) and exhibited antigen-specific, MHC class I-restricted lysis of
      peptide-pulsed T2 cells and HLA-A2+, gp100+ established melanoma cell lines.
      G10(476)- and G9(280)-specific CTLs demonstrated specific release of granulocyte
      macrophage-colony-stimulating factor and tumor necrosis factor alpha in response
      to T2 cells pulsed with relevant peptide, as well as to gp100+ melanoma cell
      lines. These results demonstrate that several peptides derived from the gp100
      protein are presented on the surface of melanoma cells and are sufficiently
      immunogenic to generate, in vitro, potent CTLs capable of cytolysis and the
      secretion of cytokines. Therefore, for HLA-A2+ melanoma patients, these and
      possibly other gp100 peptides could represent good candidates for antigen
      specific immunotherapy either singly or in a multivalent regimen.

PMID- 7585539
TI  - B7-1 and interleukin 12 synergistically induce effective antitumor immunity.
AB  - Enhanced host rejection of tumor cells is the primary goal of cancer
      immunotherapy and, in many murine tumor models, has been accomplished by
      engineering cells to express B7 costimulatory molecules or creating an
      environment rich in certain cytokines. We examined the effect of tumor cell B7-1
      expression and administered recombinant interleukin 12 (IL-12) on the syngeneic
      host response to rapidly growing, poorly immunogenic SCK mammary carcinoma cells
      and to more slowly growing, immunogenic K1735 melanoma cells. Whereas B7-1
      expression induced rejection of K1735 cells in 78% of mice, and IL-12 induced
      rejection in 38%, B7-1 expression induced rejection of SCK cells in only 28% of
      mice, and IL-12 induced rejection in none. The relative ineffectiveness of either
      B7-1 or IL-12 alone to induce rejection of SCK cells led us to combine the two
      manipulations. This resulted in rejection of SCK cells in 74% of mice and
      dramatically delayed tumor development in the remainder. Tumor rechallenge
      studies indicated that the surviving mice developed specific immunity to wild
      type SCK cells. Lymphocyte subset ablation and IFN-gamma depletion studies
      indicated that rejection of SCK tumor cells brought about by the synergistic
      effects of B7-1 and IL-12 is mediated by a rapidly developing, systemic antitumor
      immune response that is dependent on the presence of both CD8+ and CD4+ T cells
      and involves IFN-gamma. Additionally, the synergistic effect of B7-1 expression
      and IL-12 administration is capable of inducing rejection of control SCK tumors
      simultaneously established in the opposite flank. The efficacy of B7-1 and IL-12
      in inducing protective immunity against a poorly immunogenic, aggressive murine
      tumor indicates that this combination is particularly effective at producing a
      potent antitumor immune response that may be of therapeutic benefit.

PMID- 7585541
TI  - Loss of heterozygosity on the short arm of chromosome 8 in male breast
      carcinomas.
AB  - Identification of loss of heterozygosity (LOH) at specific genetic loci in
      neoplastic cells suggests the presence of a tumor suppressor gene within the
      deleted region. LOH on chromosome 8p has been identified in colorectal, bladder,
      hepatocellular, and prostatic carcinomas. Little is currently known about the
      molecular events occurring during the development of male breast cancer. We
      studied LOH on chromosome 8p in 23 male breast carcinomas. Five polymorphic DNA
      markers were used: D8S136 and D8S137 on 8p12-21.3; and D8S254, D8S258, and D8S349
      on 8p22. DNA was extracted from microdissected normal and tumor cells obtained
      from formalin-fixed, paraffin-embedded tissue sections and amplified by the PCR.
      LOH was identified in 19 of 23 cases (83%) with at least one marker. Seven cases
      showed LOH only at 8p22, six cases showed LOH only at 8p12-21.3, and six cases
      showed LOH at both 8p22 and 8p12-21.3. In five of these last six cases, at least
      one locus was retained between the two deleted regions; thus, the whole short arm
      of chromosome 8 was not lost in these tumors. Our results show that there are two
      discrete areas of deletion on chromosome 8p in male breast cancer, suggesting the
      presence of one or more tumor suppressor genes that may play a role in the
      development or progression of the disease.

PMID- 7585543
TI  - Biallelic inactivation of the APC gene in hepatoblastoma.
AB  - Familial adenomatous polyposis (FAP) is an inherited disorder caused by germline
      mutation of the adenomatous polyposis coli (APC) gene. Increased risk of
      hepatoblastoma (HBL) in FAP kindreds has been reported. To determine whether
      inactivation of the APC gene plays a role in development of HBL, 13 sporadic
      infantile hepatic tumors were analyzed for genetic alterations in the APC gene. A
      PCR-mediated RNase protection analysis was performed to detect subtle genetic
      alterations in the mutation cluster region and in exons 3 and 4 of the APC gene.
      The results showed that a G to T transversion at the splice acceptor site of the
      intron 3-exon 4 junction had occurred in one HBL. Sequence analysis of normal
      tissue of the patient proved the mutation to be germinal. Southern blot analysis
      at the APC locus revealed that the tumor had lost the opposite allele and was
      isodisomic at this locus. RNA analysis indicated that the tumor contained only
      the small APC transcript, from which exon 4 was entirely absent. Since abnormal
      splicing causes termination due to frameshift, it was hypothesized that only the
      truncated APC protein was expressed in this tumor. These findings suggest that
      inactivation of the APC gene is closely related to tumorigenesis of HBLs in FAP
      patients.

PMID- 7585540
TI  - Interleukin 15 induction of lymphokine-activated killer cell function against
      autologous tumor cells in melanoma patient lymphocytes by a CD18-dependent,
      perforin-related mechanism.
AB  - Interleukin 15 (IL-15) is a novel cytokine that shares no homology with IL-2, but
      it requires the use of beta and gamma chains of the IL-2 receptor complex for
      binding and signaling. In vitro studies have shown induction of CTL and
      lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear
      cells (PBMCs) from normal donors by IL-15 against known tumor targets. The
      present study attempts to define the role of IL-15 in generating LAK activity
      from melanoma patient lymphocytes. PBMCs of patients newly diagnosed with
      metastatic melanoma were incubated with different doses of recombinant human IL
      15 and tested against autologous tumor cells, LAK sensitive cell lines (i.e.,
      FMEX and Daudi), as well as the natural killer-sensitive cell line K562, in a 15
      h 51Cr release assay. The effect of IL-15 was found to be both time and dose
      dependent, with peak activity detected after 2 or 3 days of culture with 100
      ng/ml of this cytokine. LAK and not CTL activity in patient PBMCs was detected by
      the inability of mAbs against CD4, CD8, and MHC class I to effectively block
      lysis of autologous tumor and FMEX melanoma cells. In addition, interaction via
      the CD18 adhesion molecule was shown to be critical in IL-15-induced LAK-mediated
      lysis of autologous tumor cells. Finally, incubation of patient PBMCs with IL-15
      for 6 h resulted in the up-regulation of perforin mRNA transcription. These
      findings suggest that LAK activity can be generated from melanoma patient PBMCs
      in the presence of IL-15 to lyse autologous tumor cells in a non-MHC-restricted
      manner. This new cytokine may play an important role in antitumor immunity with a
      possible use for cancer immunotherapy.

PMID- 7585544
TI  - Differences between Burkitt's lymphomas and mouse plasmacytomas in the
      immunoglobulin heavy chain/c-myc recombinations that occur in their chromosomal
      translocations.
AB  - Burkitt's lymphomas (BLs) and mouse plasmacytomas (MPs) are characterized by
      chromosomal translocations juxtaposing the c-myc oncogene to one of the
      immunoglobulin loci. Here we describe illegitimate recombinations and the DNA
      sequence at the junction between c-myc and immunoglobulin heavy chain (IgH)
      regions in these B-cell lineage tumors. In 15 BLs and in 29 MPs, recombination
      products were amplified by PCR and sequenced. Molecular analysis of the IgH/c-myc
      junctions revealed the following characteristics: (a) rearrangements in BLs
      represent nearly reciprocal exchanges between c-myc and IgH switch sequences,
      whereas in MPs, several hundred bp of c-myc may be duplicated or deleted; (b)
      short homologies of up to 5 bp between immunoglobulin and c-myc sequences can be
      found at most junction sites in both tumors; and (c) pentameric sequences
      typically found in switch regions and V(D)J recognition motifs also occur
      frequently at the sites of recombination in c-myc.

PMID- 7585542
TI  - Estradiol regulation of the human retinoic acid receptor alpha gene in human
      breast carcinoma cells is mediated via an imperfect half-palindromic estrogen
      response element and Sp1 motifs.
AB  - Estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines express
      significantly higher levels of retinoic acid receptor alpha (RAR alpha) (isoform
      1) mRNA than ER-negative HBCs. Estradiol enhances RAR alpha mRNA expression in
      different ER-positive HBCs by 2-3-fold, which in turn results in increased
      sensitivity of ER-positive HBCs to the growth inhibitory effects of retinoic
      acid. To investigate the regulatory mechanisms of estradiol-mediated enhancement
      of RAR alpha mRNA expression, the functional promoter for the human RAR alpha
      isoform 1 was cloned and used to assess estradiol-mediated promoter-dependent
      enhancement of firefly luciferase reporter gene activity in transiently
      transfected ER-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231) HBCs.
      Deletional promoter constructs were obtained to further delineate the promoter
      region responsible for estradiol-mediated enhancement of promoter activity. Here,
      we present evidence that approximately 130 bp of the promoter fragment preceding
      the transcriptional start site are responsible for estradiol-mediated enhancement
      of hRAR alpha gene expression. The estradiol-mediated enhancement is dependent on
      ER binding. Further deletional analysis showed that a promoter sequence of 42
      base pairs, located approximately 100 bases upstream of the transcriptional start
      site, contains elements for estradiol-mediated enhancement. Specific deletion of
      either the Sp1 motif or mutations in the imperfect half-palindromic estrogen
      response element motif of this fragment abolish its estradiol responsiveness in
      transient transfections.

PMID- 7585546
TI  - Simultaneous amplification of four DNA repair genes and beta-actin in human
      lymphocytes by multiplex reverse transcriptase-PCR.
AB  - We describe here the development, optimization, and use of a non-radioactive,
      quantitative, multiplex reverse transcriptase-PCR technique to measure, in a
      single reaction, the relative levels of the transcripts of four DNA repair genes
      (XPCC, hMSH2, XRCC1, and ERCC1) and the beta-actin gene in lymphoblastoid cell
      lines and frozen peripheral blood lymphocytes. Expression of defective DNA repair
      genes was not detected in DNA repair-deficient human cell lines, whereas the
      intact genes were detected in repair-proficient cell lines and in lymphocytes
      from a normal donor. The assay was reproducible, and repeated determinations of
      the same samples generated highly consistent results for each target gene. This
      approach should facilitate molecular epidemiological studies that incorporate
      screening for germline alterations that may affect gene expression and for
      changes in the levels of gene expression.

PMID- 7585548
TI  - Aberrant p53 expression predicts clinical resistance to cisplatin-based
      chemotherapy in locally advanced non-small cell lung cancer.
AB  - The development of cisplatin-based induction chemotherapy followed by surgical
      resection or radiation has improved the poor prognosis of stage III non-small
      cell lung cancer (NSCLC). In vitro studies indicate that p53 can modulate
      cisplatin-induced cytotoxicity, but the molecular genetic features determining
      response or resistance to cisplatin in vivo must be defined. For this reason,
      tumor specimens from 52 patients with stage IIIA NSCLC entered in a prospective
      clinical trial of cisplatin-based induction chemotherapy followed by surgical
      resection were examined for p53 expression by immunohistochemical staining before
      and after induction chemotherapy. p53 expression was correlated with clinical and
      pathological response using Fisher's exact test. No correlation was established
      between p53 expression and clinical response because 47 of the 52 patients
      studied had a major response. However, a significant association was observed
      between aberrant p53 expression and resistance to chemotherapy as assessed by
      pathological response. Only 3 of the 20 patients whose tumors exhibited a high
      level (+ + to + + + +) of p53 staining experienced a major (+ + + to + + + +)
      pathological response to chemotherapy. Only 7 of 52 cases examined before and
      after chemotherapy treatment exhibited a change in the level of p53 expression
      after cisplatin-based chemotherapy. These results indicate that cisplatin alters
      p53 expression infrequently and suggest a direct link between aberrant p53
      expression and resistance to cisplatin-based chemotherapy in NSCLC.

PMID- 7585547
TI  - Distinct nonrandom patterns of chromosomal aberrations in the progression of
      squamous cell carcinomas of the head and neck.
AB  - Fifty-one randomly selected primary squamous cell carcinomas of the head and
      neck, derived from the larynx (n = 18) and pharynx (oropharynx, n = 18, and
      hypopharynx, n = 15) were analyzed with centromeric probes for chromosomes 1, 7,
      9, 11, 17, and 18 to study numerical aberrations, chromosome imbalances, and
      aneuploidy by fluorescence in situ hybridization. The tumors were grouped into
      nonmetastasizing (N0) tumors (from patients clinically free of lymph node
      metastases for at least 18 months after surgery, n = 25) and metastasizing (N1-3)
      tumors (n = 26). We found a significant association between the tumor ploidy and
      the nodal status; in the N0 group, diploidy prevailed, and the most common
      aberration was loss to monosomy for chromosome 9 (44%), whereas in the N1-3
      group, aneuploidy predominated (P = 0.002). Specifically, these genomic changes
      associated with progression to metastasis were: (a) tetrasomic or polysomic
      chromosomes were detected in 17 of 26 N1-3 tumors but in none of the 25 N0 tumors
      (P < 0.0001); (b) heterogeneous chromosomal copy numbers (i.e., extensive
      chromosomal imbalances) were also much more frequent in the N1-3 tumors (69.2%
      versus 24.0% in the N0 group; P = 0.018); and (c) loss of chromosome 9 (73%) and
      gains of chromosomes 7 (35%) and 17 (31%) persisted, but in addition, loss of
      chromosome 18 occurred in 31%. Overexpression of the p53 protein correlated with
      an increased incidence of chromosomal imbalances and aneuploidy (P < 0.001) and,
      hence, constituted an additional risk factor. The lower metastatic potential of
      larynx tumors as compared with tumors from the pharynx was reflected by a lower
      incidence of these genomic changes. These specific patterns of chromosomal
      aberrations can characterize and distinguish different stages of tumor
      progression of squamous cell carcinomas of the head and neck and should be
      valuable diagnostic and prognostic markers.

PMID- 7585545
TI  - Expression of cell cycle regulatory factors in differentiating osteoblasts:
      postproliferative up-regulation of cyclins B and E.
AB  - The representation of cyclins and cyclin-dependent kinases (cdks) was analyzed
      during progressive development of the bone cell phenotype in cultures of normal
      diploid rat calvarial osteoblasts. Three developmental stages were examined: (a)
      proliferation; (b) monolayer confluency; and (c) mineralization of the bone
      extracellular matrix. We demonstrate that the presence of cyclins and cdks is not
      restricted to the proliferation period. Consistent with their role in cell cycle
      progression, cdc2 and cdk2 decrease postproliferatively. However, cdk4 and
      cyclins A, B, and D1 persist in confluent cells. Cyclin E is significantly up
      regulated during the extracellular matrix mineralization developmental period.
      Examination of the cytoplasmic levels of these cell cycle regulatory proteins
      indicates a marked increase in cyclin B in the late differentiation stage. The
      elevation of nuclear cyclin E and cytoplasmic cyclin B is not observed in
      osteoblasts maintained under culture conditions that do not support
      differentiation. Furthermore, treatment with transforming growth factor beta for
      48 h during the proliferation period renders the cells incompetent for
      differentiation and abrogates the postproliferative up-regulation of cyclins B
      and E. Density-induced growth inhibition of ROS 17/2.8 osteosarcoma cells is not
      accompanied by up-regulation of nuclear cyclin E and cytoplasmic cyclin B when
      compared to the proliferation period. This observation is consistent with
      abrogation of both growth control and differentiation regulatory mechanisms in
      tumor cells. These results suggest that cell cycle regulatory proteins function
      not only during proliferation but may also play a role in normal diploid
      osteoblast differentiation.

PMID- 7585550
TI  - Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and
      carcinomas with clinicopathological correlations.
AB  - Angiogenesis is a crucial step in tumor growth and progression. Its quantitation
      by microvessel counting is of prognostic value in several types of malignancies.
      Scarce data are available on angiogenesis in gastrointestinal tumors. We studied
      36 adenomas and 178 large bowel carcinomas to evaluate the onset of angiogenesis
      in colorectal tumorigenesis and to assess the prognostic significance of
      microvessel quantitation. Endothelial cells were immunostained with an anti-CD31
      mAb; in each case three microscopic fields (x 200) with the highest number of
      microvessels were counted: the average value of the three fields was used to
      evaluate the significance of microvessel density (MVD). MVD of normal mucosa (41
      cases) served as controls. MVD was 42 +/- 10 in the normal mucosa, 64 +/- 10 in
      adenomas, and 115 +/- 39 in carcinomas (normal versus adenomas, P < 0.001;
      adenomas versus carcinomas, P < 0.0001). The transitional mucosa adjacent to
      carcinomas displayed intermediate levels of MVD (89 +/- 23; P < 0.001 versus
      adenomas; P < 0.001 versus carcinomas). High MVDs were not associated with
      metastases, disease stage, and patient survival. The data indicate that
      angiogenesis is an early, critical step in colorectal tumorigenesis. MVD,
      however, does not provide significant prognostic information in colorectal cancer
      patients.

PMID- 7585549
TI  - Regulation of the expression of E-cadherin on human cancer cells by gamma
      linolenic acid (GLA).
AB  - E-cadherin is a cell to cell adhesion molecule which acts as a suppressor of
      metastasis. This study examined the effect of gamma-linolenic acid (GLA), a n-6
      polyunsaturated fatty acid, on the expression of E-cadherin in human cancer
      cells. Western blotting studies demonstrated that treatment of cells with GLA for
      24 h increased the expression of E-cadherin in lung, colon, breast, melanoma, and
      liver cancer cells, but not in endothelial cells and fibroblasts. The results
      were confirmed by immunocytochemistry. In contrast, two other n-6 fatty acids,
      linoleic acid and arachidonic acid, failed to induce these changes. The increased
      expression of E-cadherin was correlated with reduced in vitro invasion and
      increased aggregation, indicating that the increased E-cadherin expression
      induced by GLA was biologically active. These data add GLA to the short list of E
      cadherin up-regulatory factors. The up-regulation of E-cadherin expression in
      human cancer cells may contribute to the anticancer properties of GLA.

PMID- 7585552
TI  - Characterization of progesterone receptor A and B expression in human breast
      cancer.
AB  - The human progesterone receptor (PR) is a ligand-activated nuclear transcription
      factor that mediates progesterone action in target tissues. Two PR proteins, PR-A
      (M(r) 81,000-83,000) and PR-B (M(r) 116,000-120,000), have been described and
      different physiological activities ascribed to each on the basis of in vitro
      studies, suggesting that their ratio of expression may control progesterone
      responsiveness in target cells. Presence of PR in breast tumors is an important
      indicator of likely responsiveness to endocrine agents. However, the relative
      expression of PR-A and B in breast cancer has not been described, and its
      clinical significance has not been addressed. Expression of PR-A and B was
      measured by immunoblot analysis of 202 PR-positive human breast tumor cytosols.
      The ratio of expression of the two PR proteins (PR-A/B) ranged from 0.04 to
      179.3. The median PR-A/B ratio was 1.26, and 61.4% of samples had PR-A/B ratios
      between 0 and 2. PR-A/B ratios deviated significantly from a normal log
      distribution; tumors containing a PR-A/B ratio greater than 4 were
      overrepresented in the group. Linear regression analysis revealed that high PR
      A/B ratios, in general, derived from a low concentration of PR-B rather than high
      expression of PR-A. PR-A/B protein ratios were not correlated with the age of the
      patient or with total PR concentration. A third PR protein band (PR78kDa) was
      detected in a number of samples and comprised greater than 20% of total PR
      protein in 52 (25.7%) of the 202 tumor samples examined. The range or frequency
      distribution of PR-A/B ratios in samples containing PR78kDa was not different to
      the overall group. In summary, in PR-positive breast tumors, the ratio of
      expression of PR-A and B proteins is close to unity, as is seen in a number of
      other progestin target tissues. However, a significant proportion of tumors
      expressed very low levels of PR-B and a consequently high PR-A/B ratio. Although
      the clinical consequence of this observation is not known, the in vitro findings
      that PR-A may act as a repressor of PR-B suggest that tumors containing primarily
      PR-A may identify a subset of patients with low or aberrant response to endocrine
      agents.

PMID- 7585551
TI  - Egr-1 negatively regulates human tumor cell growth via the DNA-binding domain.
AB  - Human HT1080 fibrosarcoma cells, subclone H4, express little or no Egr-1
      (Zif/268, Krox 24), an early growth response gene encoding a transcription
      factor. Phorbol ester (but not serum) treatment only can elicit a small increase
      in Egr-1 expression in H4, in contrast to the normally rapid, high transient
      expression of Egr-1 observed after the addition of a wide range of stimulating
      agents to normal or immortalized cell lines. Because several human tumor cell
      lines express little Egr-1, we tested the hypothesis that this loss was causal to
      transformation. We report here that the expression of exogenous mouse Egr-1 in H4
      cells inhibits transformed growth in a dose-dependent manner and significantly
      suppresses tumorigenicity in athymic mice. By overexpression of the fragment in
      Egr-1 that is responsible for its DNA-binding activity, the zinc-finger domain,
      we show that this domain has a similar activity. Moreover, the expression of
      antisense mRNA encoding the DNA-binding domain increases the transformed
      character of the H4 cells. One possible conclusion is that endogenous Egr-1-like
      genes perform growth-regulatory functions. Other human tumor lines are also
      growth suppressed by Egr-1 overexpression including ZR-75-1 breast carcinoma,
      U251 glioblastoma, and to a lesser extent, SAOS-2 osteosarcoma cells. These
      results are surprising in light of the "early growth response" character of Egr-1
      but extend our earlier report of suppression of growth in v-sis-transformed
      NIH3T3 cells.

PMID- 7585553
TI  - Cell cycle constraints on peroxide- and radiation-induced inhibitory checkpoints.
AB  - The growth of human skin fibroblasts was reduced in a dose-dependent manner after
      either treatment with hydrogen peroxide or exposure to ionizing radiation. Serum
      starved cells were markedly responsive to the inhibitory properties of large
      doses of either agent at any time during the first 12-14 h after restimulation.
      In contrast, when logarithmically growing cells were treated with hydrogen
      peroxide, a large percentage of G1 cells synchronously traversed S phase in a
      wave that appeared after a 3-4 h delay, with a population of these cells
      eventually arresting in late S and G2. An analogous compartment of cells exiting
      G1 was not obvious when logarithmically growing cells were treated with ionizing
      radiation alone. However, when irradiated cells were subsequently treated for 4 h
      with aphidicolin to depress ongoing DNA synthesis to the levels seen in cultures
      treated with peroxide, a similar pattern of cells synchronously exiting G1 was
      seen. Therefore, although cells between G0 and S had a marked sensitivity to the
      inhibitory effects of either peroxide or radiation, logarithmically growing cells
      in G1 between M and S were far less susceptible to either type of growth
      inhibition.

PMID- 7585556
TI  - Invasion of selectively permeable sea urchin embryo basement membranes by
      metastatic tumor cells, but not by their normal counterparts.
AB  - The selectively permeable basement membranes and the associated extracellular
      matrix of sea urchin embryos can be obtained intact. Their exterior surfaces have
      been used as invasion substrates for metastatic melanoma, squamous cell
      carcinoma, and fibrosarcoma cells, for primary squamous cell carcinoma cells, and
      for neonatal melanocytes, fibroblasts, and keratinocytes. About 18% of all
      metastatic tumor cells placed in contact with sea urchin embryo basement
      membranes and their associated extracellular matrix invaded them. About 4% of the
      cells of a primary squamous cell carcinoma, which later metastasized, invaded
      these substrates. As expected, neonatal melanocytes, keratinocytes, and
      fibroblasts failed to invade; however, melanocytes treated with scatter factor
      (hepatocyte growth factor) invaded as efficiently as metastatic tumor cells. This
      suggests that the lack of invasion by epidermal melanocytes is not due to
      irreversible differentiation to a noninvasive phenotype. Invasion time courses
      showed that the metastatic cells tested reached their maximal invasion
      frequencies in 4 h; thus, invasion of these substrates is rapid and efficient.
      This suggests that molecules participating in basement membrane recognition and
      invasion have been functionally conserved during the time separating vertebrates
      from invertebrates and that their constitutive activity may allow metastatic
      cells to escape their tissues of origin.

PMID- 7585555
TI  - X chromosome inactivation in the normal female genital tract: implications for
      identification of neoplasia.
AB  - Monoclonal proliferative lesions may be identified by X chromosome inactivation
      skewing relative to normal polyclonal tissues. We have quantitatively analyzed X
      inactivation patterns throughout polyclonal uterine tissues to develop
      interpretive criteria for recognition of monoclonal neoplasms. Six fresh tissue
      samples (two samples each of cervix, endometrium, and myometrium) were collected
      from hysterectomy specimens, and the percentage of androgen receptor (HUMARA)
      marker allele present on inactive X chromosomes was calculated from a PCR assay.
      Exact balancing yields 50% of the marker on the inactive X, whereas complete
      skewing shows either 0 or 100%. X inactivation was similar throughout the tissues
      of each uterus but was significantly different among the 11 women studied.
      Comparison of differences in X inactivation between pairs of polyclonal tissue
      samples within each uterus (Xi spread) permitted delineation of cumulative
      experimental and biological variation of this parameter. Polyclonal-polyclonal Xi
      spread averaged 10.7 and was independent of the tissue type, sampling site, or
      the individual studied. Severe baseline skewing of reference polyclonal tissues
      or contamination of monoclonal tissue by polyclonal cells may reduce the
      polyclonal-monoclonal Xi spread. The extent of X-inactivation skewing necessary
      to infer a monoclonal process should exceed the 20 or 27 point spread seen,
      respectively, between 85 and 95% of polyclonal samples.

PMID- 7585554
TI  - Inhibition of fibroblast growth factor 2 expression by antisense RNA induced a
      loss of the transformed phenotype in a human hepatoma cell line.
AB  - Fibroblast growth factor 2 (FGF-2 or basic FGF) is associated with the cell
      transformed phenotype. To clarify the function of FGF-2 in the malignancy of
      tumor cells, we designed experiments to express antisense RNA in a hepatoma cell
      line. Using FGF-2 mRNA, alternative initiations of translation at one AUG and
      three CUG start codons led to the synthesis of four isoforms. SK-Hep1 cells,
      which naturally produce the four FGF-2 proteins, were stably transfected with
      expression vectors that generate antisense RNAs targeted against different sites
      of human FGF-2 mRNA. A variable decrease of all of the isoforms of FGF-2
      synthesis was observed compared with the control: the strongest inhibition was
      obtained with the smaller antisense targeted against AUG codon. Our results
      clearly demonstrated that inhibition of FGF-2 expression led to a loss of
      anchorage independence in soft agar. This effect was not reversed by adding
      exogenous FGF-2, indicating that an intracrine process of FGF-2 probably is
      involved in the phenotypic changes of SK-Hep1 cells. Furthermore, the inhibition
      of FGF-2 synthesis was correlated with a loss of tumorigenicity in nude mice.
      These results clearly argue for a key role of endogenous FGF-2 in transformation
      and tumorigenesis of the hepatoma cell line used in this study.

PMID- 7585558
TI  - Both transforming growth factor-beta and substrate release are inducers of
      apoptosis in a human colon adenoma cell line.
AB  - VACO-330, a nontransformed cell line established from a human colon adenoma,
      undergoes spontaneous apoptosis and shedding of cells into the culture medium.
      Shed cells were shown to be apoptotic, both by nuclear morphology and by
      generation of a typical "laddered" pattern of degraded DNA. Quantitation of DNA
      released into the medium, compared with the amount retained on the plate,
      demonstrated that 6.2 +/- 1.1% of the total cell mass underwent apoptotic death
      daily. The addition of transforming growth factor beta (20 ng/ml) accelerated
      this spontaneous apoptotic rate 3.2-fold. Moreover, apoptosis could be rapidly
      induced in up to 45% of the VACO-330 cells by using brief exposure to a calcium
      chelating medium to release the cells from the substratum. We suggest that
      transforming growth factor beta is a likely physiological regulator of apoptosis
      during maturation of the colonic epithelial cells. We additionally suggest the
      existence of an alternate pathway, which at the time of shedding from the crypt
      induces apoptosis in colonic epithelial cells that have escaped earlier apoptotic
      signals.

PMID- 7585557
TI  - Antigenic cancer cells that escape immune destruction are stimulated by host
      cells.
AB  - Cancers induced by UV light in murine skin often regress completely when
      transplanted into normal syngeneic recipients and grow progressively only in T
      cell-deficient hosts. Heritable cancer variants that grow progressively and kill
      normal mice occasionally evolve in vivo. It is surprising that most of these
      variants appear to retain their antigenicity and immunogenicity. We have compared
      three such variants (4102-PRO, 6132A-PRO, and 6134-PRO) with the parental tumors
      to determine why the variants acquired progressive phenotypes without antigen
      loss. We found that all three variants grew substantially faster than the
      parental tumors in T-cell-deficient hosts; one variant, 6132-PRO, also grew
      faster in vitro. Furthermore, the growth of all of the variants was stimulated by
      soluble factors released by tumor-induced peritoneal exudate cells, and all
      attracted more leukocytes than the parental cells. Finally, pretreatment of mice
      with antigranulocyte antibody reduced the growth of variant but not parental 4102
      and 6134A tumor cells. The treatment reduced the growth of both the parental and
      the variant 6132A lineage cells. We found no evidence for acquired resistance of
      variant tumors to immune destruction by a host defense mechanism. The parental
      cells did not grow faster in beige nude mice deficient in natural killer and
      alpha beta T cells or in SCID mice deficient in B and T cells. The variant
      parental cells had a similar sensitivity to lysis by polyinosinic-polycytidic
      acid-induced natural killer cells or thioglycolate- and LPS-induced macrophages.
      Together, our results are consistent with the notion that these variants escape
      from immune destruction in vivo by attracting leukocytes that stimulate tumor
      cell growth.

PMID- 7585560
TI  - Evidence of cumulative gene losses with progression of premalignant epithelial
      lesions to carcinoma of the bronchus.
AB  - Human bronchial carcinoma is thought to develop through progressive stages from
      basal cell hyperplasia to squamous metaplasia, dysplasia, carcinoma in situ, and
      finally invasive cancer. In this study, we used tissue microdissection to examine
      loss of heterozygosity of chromosomes 3p21, 5q21, and 9p21 at each stage of the
      epithelial progression to invasive cancers. Forty-eight premalignant/malignant
      bronchial sites were biopsied from 13 patients (including 9 subjects without
      cancer) using fluorescence bronchoscopy. Eighteen sites with moderate/severe
      dysplasia in 6 patients were subjected to bronchoscopic and molecular follow-up
      during a 3-month to 2-year period. Seven separate cases of advanced non-small
      cell bronchial cancers were also analyzed. From the baseline biopsies, the
      prevalence of 3p and 9p deletions increased significantly from no deletion in the
      hyperplasia/metaplasia samples (n = 9) to 37 and 31% of the informative cases,
      respectively, in the dysplasia samples (n = 29), to 100 and 83%, respectively,
      for the carcinomas in situ (n = 6), and 100% in the invasive cancers (n = 11).
      Chromosome 5q deletion was significantly more frequent in invasive cancers (70%
      of the informative cases) as compared to carcinoma in situ (40%), dysplasias
      (33%), and hyperplasia/metaplasia samples (11%). The number of chromosome
      alterations also increased significantly from the lowest to the highest grade
      lesions, showing evidence of accumulation of genetic damage from one group to
      another. The molecular follow-up analysis showed that the same genomic alteration
      can persist in a given dysplastic bronchial area for several months or years, and
      that the persistence or the regression of the molecular abnormality is well
      correlated with the evolution of the disease on follow-up. Our results suggest
      that molecular analysis of bronchial biopsies obtained by fluorescence
      bronchoscopy may be a very useful means to study the natural history of
      preinvasive bronchial lesions and the outcome of interventions, such as with
      chemopreventive treatment.

PMID- 7585559
TI  - SCH 51344 inhibits ras transformation by a novel mechanism.
AB  - A pyrazolo-quinoline compound, 6-methoxy-4-[2-[(2-hydroxyethoxyl)-ethyl]amino]-3
      methyl-1M-pyrazo lo [3,4-b]quinoline (SCH 51344), was identified based on its
      ability to derepress human smooth muscle alpha-actin promoter activity in ras
      transformed cells. In this study, we show that SCH 51344 reverts several key
      aspects of ras transformation, such as morphological changes, actin filament
      organization, and anchorage-independent growth, and also inhibits Val-12 Ras
      induced maturation of Xenopus oocytes. SCH 51344 is also a potent inhibitor of
      the anchorage-independent growth of human tumor lines known to contain multiple
      genetic alterations in addition to activated ras genes. We have sought to
      determine whether SCH 51344 disrupts the signaling pathway that activates mitogen
      activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) in
      normal and ras-transformed fibroblast cells. NIH 3T3 cells transformed by
      different oncogenes, which have products that participate at different steps of
      the Ras signaling pathway, were tested in a soft-agar colony formation assay to
      determine which step of the pathway is inhibited by SCH 51344. Our results
      indicate that SCH 51344 inhibits the ability of v-abl, v-mos, H-ras, v-raf, and
      mutant active MAP kinase kinase-transformed NIH 3T3 cells to grow in soft agar.
      Only v-fos-transformed cells were found to be resistant to the treatment of SCH
      51344. SCH 51344 treatment had very little effect, if any, on the activation of
      MAP kinase kinase, MAP kinase, and p90RSK activity in response to growth factor
      stimulation. Treatment of ras-transformed cells with SCH 51344 led to stimulation
      of serum response factor DNA binding activity and activation of serum response
      element-dependent gene transcription, accounting for its ability to activate
      alpha-actin promoter activity in ras-transformed cells. Our results indicate that
      SCH 51344 inhibits ras transformation by a novel mechanism and acts at a point
      either downstream or parallel to extracellular signal-regulated kinase-dependent
      Ras signaling pathway.

PMID- 7585561
TI  - Pyruvate utilization, phosphocholine and adenosine triphosphate (ATP) are markers
      of human breast tumor progression: a 31P- and 13C-nuclear magnetic resonance
      (NMR) spectroscopy study.
AB  - We have used 31P- and 13C-nuclear magnetic resonance spectroscopy to measure key
      metabolite levels and fluxes through enzymes regulating phospholipid and
      mitochondrial metabolism in normal human mammary epithelial cells. We have
      compared these values to those found in a progression series of breast cancer
      cell lines of varying metastatic potential established from a single patient. We
      find a 16-19-fold increase in phosphocholine content in two primary breast cancer
      cell lines (21PT and 21NT) and a 27-fold increase in phosphocholine content in
      the metastatic breast cancer cell line (21MT-2) compared with the normal breast
      epithelial cell strain 76N. Thus, phosphocholine may serve as a metabolic marker
      for the human breast cell progression state. A 30% decrease in ATP levels, a 83%
      decrease in phosphocreatine levels, along with a 2-fold increase in NAD(+) + NADH
      levels in 21PT, 21NT, and 21MT-2 cells compared to the normal breast cells
      further suggests impaired mitochondrial metabolism in the breast carcinoma cell
      lines. Consistent with this suggestion is our finding that the primary breast
      cancer cell lines (21PT and 21NT) and the metastatic breast cell line (21MT-2)
      showed a 50 and 89% relative reduction, respectively, in the flux of pyruvate
      utilized for mitochondrial energy generation compared to pyruvate utilized to
      replenish tricarboxylic acid cycle intermediates. These results demonstrate that
      diminished mitochondrial energy generation may be quantitatively related to the
      progression state of human breast cells.

PMID- 7585562
TI  - Differential cellular expression of the human MSH2 repair enzyme in small and
      large intestine.
AB  - The human MSH2 (hMSH2) protein is responsible for the initial recognition of
      mismatched nucleotides during the postreplication mismatch repair process. Loss
      of hMSH2 function has been demonstrated to lead to the accumulation of
      replication errors, resulting in a mutator phenotype, which may be responsible
      for the multiple mutations required for multi-stage carcinogenesis. Alterations
      of the hMSH2 gene has been linked to approximately 60% of hereditary nonpolyposis
      colon cancer cases. Colon tumors in hereditary nonpolyposis colon cancer patients
      originate within benign preneoplastic adenomas and display replication errors in
      the form of microsatellite instability. The aim of this study was to investigate
      the cellular expression of the hMSH2 protein in cells of the large and small
      intestines. Using antibody specific for hMSH2, we have determined that this
      protein is highly expressed in cells of the crypts of Lieberkuhn that are
      undergoing rapid renewal in both the ileum and colon. Proliferative
      perifibroblasts in the colon also showed significant presence of the hMSH2
      protein. These results confirm the hypothesis that hMSH2 is expressed in highly
      proliferative cells of the gut, and mutations in this gene could, therefore, be
      expected to expedite the progression of adenoma to carcinoma in this tissue.

PMID- 7585563
TI  - In vivo gene therapy with p53 or p21 adenovirus for prostate cancer.
AB  - We introduced the gene for wild-type human p53 or p21, a critical downstream
      mediator of p53-induced growth suppression, into a p53-deficient mouse prostate
      cancer cell line using a recombinant adenoviral vector (Ad5CMV-p53 or Ad5CMV
      p21). Elevated levels of endogenous mouse p21 mRNA provided evidence for the
      functional activity of virally transduced p53. Functional activity of viral
      transduced p21 was demonstrated through immunoprecipitation of cellular protein
      extracts, which showed that the viral-transduced p21 associates with cyclin
      dependent kinase 2 and was sufficient to down-regulate the activity of the cyclin
      dependent kinase by approximately 65%. In vitro growth assays revealed
      significantly higher growth suppression after Ad5CMV-p21 infection compared to
      Ad5CMV-p53. In vivo studies in syngeneic male mice with established s.c. prostate
      tumors demonstrated that the rate of growth and final tumor volume were reduced
      to a much greater extent in mice that received intratumor injection of Ad5CMV-p21
      compared to Ad5CMV-p53. In addition, the survival of host animals bearing tumors
      that were infected with Ad5CMV-p21, but not Ad5CMV-p53, was significantly
      extended. These data suggest that Ad5CMV-p21 may be effective as a therapeutic
      agent for prostate cancer.

PMID- 7585565
TI  - Inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) activity
      by suramin and suramin analogues is correlated to interaction with the GM-CSF
      nucleotide-binding site.
AB  - Suramin and suramin analogues strongly inhibit both nucleotide interaction with
      the nucleotide-binding site of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and bioactivity of the molecule as assessed by competition photoaffinity
      labeling and cell proliferation assay, respectively. The half-maximal inhibition
      of cell proliferation by suramin occurs at 68 +/- 2.5 microM; three suramin
      analogues achieved comparable activity. The degree of competitive inhibition of
      nucleotide-binding by these compounds and the inhibition of GM-CSF bioactivity
      are correlated such that the compounds show similar rank-order by both of these
      methods. The strong interaction of suramin and related compounds with the
      nucleotide-binding site may mimic nucleotide-mediated inhibition of GM-CSF
      bioactivity and may be an important mechanism by which suramin acts as a
      pharmacological anti-growth factor agent.

PMID- 7585564
TI  - Sodium phenylacetate induces growth inhibition and Bcl-2 down-regulation and
      apoptosis in MCF7ras cells in vitro and in nude mice.
AB  - Using a highly tumorigenic human breast cancer model (Ha-ras-transfected MCF7
      cell line) we analyzed the efficacy of the differentiation-inducing agent sodium
      phenylacetate (NaPA), both in vitro and in vivo. NaPA-treated MCF7ras cells
      showed dose-dependent growth inhibition from 2.5 to 15 mM without apparent
      toxicity. Western blot analysis showed a Bcl-2 down-regulation after 48 h
      treatment with 5 mM NaPA, together with apparition of apoptotic nuclei by DAPI
      staining. Mice bearing MCF7ras xenografts (n = 40) were treated for 2 weeks
      through s.c.-delivering osmotic pumps, followed by 6 weeks of daily i.p. NaPA
      administration. After 3 weeks, the treated tumors showed growth arrest without
      regression for the whole observation time, e.g., 12 weeks. Immunohistochemical
      analysis showed Bcl-2 down-regulation and differentiation patterns: decrease of
      Ki-67 and increase of steroid receptors (estrogen and progesterone receptors)
      compared to controls. Cells cultured from treated tumors (II.b) displayed
      pseudotrabecular disposition as MCF7ras cells treated in vitro. They also showed
      a higher NaPA sensitivity, together with 70% Bcl-2 down-regulation as compared to
      the derived cells of untreated tumors (II.a). When reinjected into nude mice,
      II.b cells induced only one poorly vascularized, noninvasive tumor (8%) with
      lower proliferation index, 100% progesterone receptor positive cells, and 35%
      terminal deoxynucleotidyltransferase-mediated dUTP-X nick end labeling (+)
      nuclei, as compared to 100% induction of highly vascularized and invasive tumors
      with 3% terminal deoxynucleotidyltransferase-mediated dUTP-X nick end labeling
      (+) nuclei induced by II.a cells.

PMID- 7585566
TI  - Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell
      cycle checkpoints.
AB  - Agents that disrupt mitochondrial function were used to monitor the contribution
      of ATP to cell cycle progression. Following nontoxic exposure to these agents,
      flow cytometric analysis of the cell population showed a significant increase in
      the proportion of cells in G1 at low doses of the agent and in G2-M at higher
      doses, in accordance with the degree of ATP reduction induced by the compound.
      These data indicate that cycling cells must maintain a minimal ATP content to
      satisfy the energy requirement of the checkpoint that allows passage through G1
      into S phase. Once committed, successful passage through G2 into mitosis is also
      conditional upon maintenance of a critical ATP content sufficient to satisfy the
      second energy-sensitive checkpoint that exists at this transition. These data
      establish a foundation for future investigations into the energy dependence of
      cell cycle events and propose novel means for cell cycle intervention.

PMID- 7585567
TI  - Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated
      mouse skin tumors.
AB  - p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and
      inhibit the cyclin D-dependent kinases, cdk4 and cdk6. Because these genes
      undergo frequent deletions and/or mutations in various human cancers, we examined
      the status and expression of the cognate mouse cdk inhibitors in a panel of 29
      cell lines, as well as in 12 primary tumors, representing different stages of
      mouse skin carcinogenesis. Deletion of p16INK4a and/or p15INK4b was seen in 8 of
      10 cell lines derived from spindle carcinomas, the most advanced stage of skin
      carcinogenesis. Five showed deletion of both genes, and three had independent
      deletions of p16INK4a or p15INK4b, but in those retaining p16INK4a, expression of
      the protein was not detected. By contrast, none of 19 more differentiated
      squamous cell lines exhibited such deletions. In several cases, primary tumor DNA
      was available, and two spindle tumors showed the same deletion pattern as
      observed in the corresponding cell lines. In apparent contrast, comparison of two
      clonally related squamous and spindle cell lines derived from a single carcinoma
      showed unusually high levels of p16INK4a and p15INK4b only in the invasive
      spindle cells. Therefore, deletion or altered regulation of p16INK4a and p15INK4b
      occur concomitantly with the loss of differentiation associated with the late
      spindle stage of tumor progression in mouse skin.

PMID- 7585568
TI  - Detection of mammary tumor virus env gene-like sequences in human breast cancer.
AB  - Mouse mammary tumor virus (MMTV) has been related to human breast cancer (BC) in
      previous studies. Although suggestive sequence homology to MMTV has been
      described in BC DNA, the presence of human endogenous retroviruses (HERs)
      confounded these results. We have selected a 660-bp sequence of the MMTV env gene
      with very low homology to HER or to any other human or viral gene. We have
      searched for sequences homologous to it using the polymerase chain reaction. DNA
      was extracted from fresh or frozen tissues using primers and probes constructed
      to detect 660 bp; for paraffin-embedded tissues, we sought 250-bp sequences by
      similar methodology. The 660-bp sequence was detected in 121 (38.5%) of the 314
      unselected BC samples, in cultured BC cells, in 2 (6.9%) of 29 breast
      fibroadenomas and in 2 (1.8%) of 107 breast specimens from reduction
      mammoplastias. The sequence was not found in normal tissues including breast,
      lymphocytes from BC patients, nor in other human cancers or cell lines. The 250
      bp sequence was detected in 60 (39.7%) of the 151 BCs, and in 1 of 27 normal
      breast samples assayed from paraffin-embedded sections. Cloning and sequencing of
      the 660 bp and 250 bp demonstrated that they are 95-99% homologous to MMTV env
      gene, but not to the known HERs nor to other viral or human genes (< 18%).
      Southern blot analysis using labeled cloned sequences showed that the 660-bp
      sequences were present in low copy number as a 7-8-kb EcoRI fragment only in
      breast cancer samples and two breast cancer cell lines that were positive by PCR.
      These data indicate that 38-40% of human breast cancers contain gene sequences
      homologous to the MMTV env gene that are absent from other tumors and tissues.
      These MMTV env gene-like sequences may play a role in the etiology of a large
      proportion of human breast cancer.

PMID- 7585569
TI  - Allelic loss and the progression of breast cancer.
AB  - To study genetic changes and the evolution of breast cancer, we assayed for loss
      of heterozygosity (LOH) in 12 sets of synchronous carcinoma in situ (CIS) and
      invasive cancer, compared to normal control DNA. Microsatellite markers were
      used, which map to each nonacrocentric autosomal arm. Eight tumor sets
      demonstrated LOH of the same allele in both concurrent invasive cancer and ductal
      CIS, for a total of 18 chromosomal loci. Three of nine tumor sets showed LOH on
      11p. In two of these sets, LOH was seen on 11p only in the invasive tumor, not
      the corresponding CIS. One of these tumors also exhibited allelic loss in the
      invasive tumor for 4 loci, all of which were retained in the noninvasive tumor.
      For two tumor sets, LOH was mirrored in matched ductal CIS, invasive tumor, and
      lymph node metastasis. The maintenance of LOH for certain loci throughout the
      stages of breast cancer suggests clonality of the cancer cells.

PMID- 7585570
TI  - Absence of secretory phospholipase A2 gene alterations in human colorectal
      cancer.
AB  - A potent modifying locus of intestinal tumorigenesis in the mouse was recently
      identified as secretory phospholipase A2 (sPLA2). The human homologue of sPLA2
      maps to chromosome 1p35, a region frequently lost in human tumors. To evaluate
      the possibility that sPLA2 was a tumor suppressor gene that was the target of the
      1p loss events, we identified polymorphisms within the human sPLA2 gene. Using
      these polymorphisms, 31% of 16 colorectal carcinomas were found to lose a sPLA2
      allele. However, sequence analysis of the complete coding region of sPLA2
      revealed no somatic mutations in the remaining allele of those tumors with
      allelic loss, nor in 18 additional colorectal cancers. Thus, sPLA2 is within the
      chromosomal region often lost during colorectal tumorigenesis, but mutations of
      this gene do not appear to play a major role in colorectal cancer development,
      and sPLA2 is unlikely to be the 1p35 tumor suppressor.

PMID- 7585571
TI  - p21 is necessary for the p53-mediated G1 arrest in human cancer cells.
AB  - DNA-damaging agents induce a p53-dependent G1 arrest that may be critical for p53
      mediated tumor suppression. It has been suggested that p21WAF1/CIP1, a cdk
      inhibitory protein transcriptionally regulated by p53, is an effector of this
      arrest. To test this hypothesis, an isogenic set of human colon adenocarcinoma
      cell lines differing only in their p21 status was created. The parental cell line
      underwent the expected cell cycle changes upon induction of p53 expression by DNA
      damage, but the G1 arrest was completely abrogated in p21-deficient cells. These
      results unambiguously establish p21 as a critical mediator of one well-documented
      p53 function and have important implications for understanding cell cycle
      checkpoints and the mechanism(s) through which p53 inhibits human neoplasia.

PMID- 7585572
TI  - Loss of transporter in antigen processing 1 transport protein and major
      histocompatibility complex class I molecules in metastatic versus primary breast
      cancer.
AB  - We studied by immunohistochemistry the HLA-allelic, beta 2-microglobulin, and TAP
      1 expression in primary breast carcinomas and related lymph node metastases.
      Thirty-three of the primary tumors and 44% of the lymph node metastases had a
      complete HLA class I loss. The higher incidence of antigenic loss in metastatic
      tumors suggests that recognition of HLA class I antigens by the host immunity
      could have an important role in the metastatic evolution of breast cancer. We
      observed a simultaneous defective expression of all three components involved in
      HLA class I expression. Since the controlling genes of heavy chain and TAP-1 are
      located in different chromosome than beta 2-microglobulin, it could be that a
      common factor exists regulating HLA class I antigenic expression. Five of 25
      (20%) primary and metastatic tumors from HLA-A2-positive individuals also had a
      selective loss. The high incidence of HLA class I loss in breast cancer patients
      shows that adjuvant immunotherapy to induce HLA class I expression could be of
      value in a subgroup of patients.

PMID- 7585574
TI  - Lack of correlation between DNA-dependent protein kinase activity and tumor cell
      radiosensitivity.
AB  - Lack of DNA-dependent protein kinase (DNA-PK) activity confers radiosensitivity
      and defective DNA double-strand break repair. Nine human malignant glioma cell
      lines were studied to determine whether differences in DNA-PK activity reflect
      differences in inherent radiosensitivity or are predictive of tumor treatment
      response. DNA-PK activity was present in all cell extracts, as were the DNA-PK
      proteins, DNA-PK catalytic subunit, Ku p70, and Ku p80. No correlation was found
      between the levels of DNA-PK activity and inherent radiosensitivity or in the
      tumor treatment response. These preliminary results suggest that variation in DNA
      PK activity may not be a determinant of clinical response in malignant glioma.

PMID- 7585573
TI  - E-cadherin expression is silenced by DNA hypermethylation in human breast and
      prostate carcinomas.
AB  - Expression of the Ca(2+)-dependent, homotypic cell:cell adhesion molecule, E
      cadherin (E-cad), suppresses tumor cell invasion and metastasis in experimental
      tumor models. Decreased E-cad expression is common in poorly differentiated,
      advanced-stage carcinomas. These data implicate E-cad as an "invasion suppressor"
      gene. The mechanism by which E-cad is silenced in advanced stage carcinomas is
      unclear. In this report, we show that: (a) the 5' CpG island of E-cad is densely
      methylated in E-cad-negative breast and prostate carcinoma cell lines and primary
      breast carcinoma tissue but is unmethylated in normal breast tissue; (b)
      treatment with the demethylating agent, 5-aza-2'-deoxycytidine, partially
      restores E-cad RNA and protein levels in E-cad-negative breast and prostate
      carcinoma cell lines; and (c) and E-cad promoter/CAT construct is expressed in
      both E-cad-positive and -negative breast and prostate carcinoma cell lines,
      indicating that these cells have the active transcriptional machinery necessary
      for E-cad expression. Our data demonstrate that frequent loss of E-cad expression
      in human breast and prostate carcinomas results from hypermethylation of the E
      cad promoter region.

PMID- 7585577
TI  - Partial allelotype of carcinoma in situ of the human bladder.
AB  - Carcinoma in situ (CIS) of the urinary bladder is an aggressive lesion that
      frequently progresses to an invasive tumor, yet the underlying molecular changes
      in this lesion are largely unknown. In this study, we microdissected 31 cases of
      CIS and examined them for loss of heterozygosity (LOH) on 13 chromosomal arms.
      Twenty-nine microsatellite markers were chosen for this analysis based on their
      location in regions previously shown to be frequently lost in primary
      transitional cell carcinoma of the bladder. LOH of chromosome 9 was a frequent
      event in these samples, occurring in 77% of these lesions, with 19 of 31 cases
      showing deletion on the 9p arm (61%) and 17 of 28 cases displaying LOH on 9q
      (61%). Fine mapping at 9p21 demonstrated that CIS also displayed a high frequency
      of homozygous deletion surrounding the p16INK4A locus, like superficial papillary
      tumors, the other form of noninvasive lesion found in the bladder. However, loss
      of 14q (70%) was frequent in CIS yet extremely rare in papillary lesions (9%).
      Other chromosomal arms showing frequent LOH included 8p (65%), 17p (60%), 13q
      (56%), 11p (54%), and 4q (52%), whereas slightly lower frequencies of loss were
      observed for 11q (36%), 4p (32%), 3p (31%), 18q (29%), and 5q (20%). CIS lesions
      already possess many of the genetic alterations displayed by invasive
      transitional cell carcinomas, potentially accounting for the aggressive nature of
      these lesions.

PMID- 7585576
TI  - Radiation-induced apoptosis: effects of cell age and dose fractionation.
AB  - The cell cycle dependence of radiation-induced apoptosis was measured using
      mitotically synchronized REC:myc(ch1) and Rat1:mycb cells. Cells in S and G2
      phases were more susceptible; the apoptotic fraction was about 0.7-0.8 as
      compared to about 0.4 for G1 cells at a dose of 10 Gy. Two-dimensional
      cytofluorimetric analysis of cells, pulsed-labeled with bromodeoxyuridine and
      then irradiated with 10 Gy, showed both G1 and G2 blocks (6-8 h) for REC:myc(ch1)
      cells but only G2 block for Rat1:mycb cells. Consistent with these results, wild
      type p53 and WAF1 (or p21), known to play a role in G1 delay, was induced by
      radiation in REC:myc(ch1) but not in Rat1:mycb cells. The cell cycle dependence
      of radiation-induced apoptosis and the absence of a G1 block for Rat1:mycb cells
      led to the prediction and observation of the novel "inverse split-dose effect,"
      i.e., a radiation dose given in two equal halves separated by a few hours yielded
      a higher level of apoptosis relative to that resulting from the same total dose
      given all at once. This effect is due to cell cycle progression from G1 to the
      more sensitive S-G2 phase during the interval between the split doses. In
      contrast, the inverse split-dose effect for apoptosis is absent for REC:myc(ch1),
      due presumably to the radiation-induced G1 delay. Parallel split-dose
      experiments, but using clonogenic survival as end points, show recovery for
      REC:myc(ch1) cells but not for Rat1:mycb cells, reflecting the influence of split
      dose, radiation-induced apoptosis.

PMID- 7585578
TI  - p53 point mutation and survival in colorectal cancer patients.
AB  - We have examined the relationship between point mutation of the p53 tumor
      suppressor gene and survival in colorectal cancer patients. We found that
      patients with tumors harboring mutated p53 genes showed a significantly poorer
      prognosis than did those patients with genes without point mutations, and,
      moreover, patient response to postoperative therapies depended significantly on
      mutation status in both adjuvant and palliative treatment cohorts. However, not
      all point mutations were the same functionally; point mutations within the
      conserved domains of the p53 tumor suppressor gene were inherently more
      aggressive than tumors with point mutations outside of these domains, and
      mutations of codon 175 were particularly aggressive. These results suggest that
      knowledge of a patient's p53 status, both with respect to the presence of point
      mutations and to the specific nature of the lesion, may be required to accurately
      predict both the course of the disease and the response of the disease to
      postoperative therapeutic interventions, especially those therapies based on the
      induction of apoptosis in the neoplastic cell.

PMID- 7585575
TI  - The differential expression of cytokeratin 18 in cisplatin-sensitive and 
      resistant human ovarian adenocarcinoma cells and its association with drug
      sensitivity.
AB  - DNA is the primary target of cis-diamminedichloroplatinum (cisplatin), but the
      drug also interacts with the cellular cytoskeleton composed of microtubules and
      intermediate filaments. It was found that the cisplatin-resistant 2008/C13* cell
      line contained markedly lower levels (6-fold) of cytokeratin 18, when compared to
      the cisplatin-sensitive 2008 cell line. Northern blot analysis revealed a
      markedly decreased level of cytokeratin 18 mRNA in the resistant cell line.
      Southern blot analysis of the DNA extracted from the two cell lines and then
      digested with HpaII and its methylation-sensitive isoschizomer, MspI, revealed no
      detectable differences in the methylation status of the cytokeratin gene. Neither
      5-azacytidine (5 microM) nor retinoic acid (1 microM) treatment enhanced the
      expression of cytokeratin 18 in the resistant cell line. However, transfection of
      full-length cytokeratin 18 cDNA into the cisplatin-resistant 2008/C13* cells
      resulted in clones with increased levels of cytokeratin 18, which was accompanied
      in the majority of clones by a marked increase in their sensitivity to cisplatin.
      These results demonstrate that modulating the expression of an intermediate
      filament protein results in sensitization of a drug-resistant human ovarian cell
      line to cisplatin.

PMID- 7585579
TI  - Failure to dephosphorylate retinoblastoma protein in drug-resistant cells.
AB  - Hypophosphorylation of retinoblastoma protein (RB) accompanies the DNA damage
      induced, p53-independent G1 arrest and apoptosis in two p53-null human leukemic
      cell lines, HL-60 and U937 (Q.P. Dou et al., Proc. Natl. Acad. Sci. USA, 92: 9019
      9023, 1995). When an HL-60 cell line resistant to cytosine arabinoside was
      exposed to this DNA-damaging agent, neither RB hypophosphorylation nor apoptosis
      were observed. In contrast, treatment of these cells with another DNA-damaging
      agent, etoposide, dramatically induced these events, which were inhibitable by
      the addition of zinc chloride, a protein tyrosine phosphatase inhibitor.
      Induction of hypophosphorylation of RB may be an important novel strategy for
      treating drug-resistant cancers.

PMID- 7585580
TI  - Polymorphism in the N-acetyltransferase 1 (NAT1) polyadenylation signal:
      association of NAT1*10 allele with higher N-acetylation activity in bladder and
      colon tissue.
AB  - Exposures to carcinogens present in the diet, in cigarette smoke, or in the
      environment have been associated with increased risk of bladder and colorectal
      cancer. The aromatic amines and their metabolites, a class of carcinogen
      implicated in these exposures, can be N- or O-acetylated by the NAT1 and NAT2
      enzymes. Acetylation may result in activation to DNA-reactive metabolites or, in
      some cases, detoxification. Many studies have focused on genetic variation in
      NAT2 and its potential as a risk factor in bladder and colorectal cancer;
      however, NAT1 activity is higher in bladder and colonic mucosa than NAT2, and the
      NAT1 enzyme also exhibits phenotypic variation among human tissue samples. We
      hypothesized that specific genetic variants in the polyadenylation signal of the
      NAT1 gene would alter tissue levels of NAT1 enzyme activity and used a PCR-based
      method to distinguish polymorphic NAT1 alleles in samples obtained from 45
      individuals. When the NAT1 genotype was compared with the NAT1 phenotype in
      bladder and colon tissue samples (p-aminobenzoic acid activity), we observed a
      approximately 2-fold higher NAT1 enzyme activity in samples from individuals who
      inherited a variant polyadenylation signal (NAT1*10 allele). This is the first
      observation relating a genetic polymorphism in NAT1 to a rapid/slow NAT1
      phenotype in humans.

PMID- 7585581
TI  - Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA
      adduct formation in the human urinary bladder.
AB  - The metabolic activation and detoxification pathways associated with the
      carcinogenic aromatic amines provide an extraordinary model of polymorphisms that
      can modulate human urinary bladder carcinogenesis. In this study, the metabolic N
      acetylation of p-aminobenzoic acid (PABA) to N-acetyl-PABA (NAT1 activity) and of
      sulfamethazine (SMZ) to N-acetyl-SMZ (NAT2 activity), as well as the O
      acetylation of N-hydroxy-4-aminobiphenyl (OAT activity; catalyzed by NAT1 and
      NAT2), were measured in tissue cytosols prepared from 26 different human bladder
      samples; then DNA was isolated for determination of NAT1 and NAT2 genotype and
      for analyses of carcinogen-DNA adducts. Both PABA and OAT activities were
      detected, with mean activities +/- SD of 2.9 +/- 2.3 nmol/min/mg protein and 1.4
      +/- 0.7 pmol bound/mg DNA/min/mg protein, respectively. However, SMZ activities
      were below the assay limits of detection (< 10 pmol/min/mg protein). The levels
      of putative carcinogen-DNA adducts were quantified by 32P-postlabeling and
      averaged 2.34 +/- 2.09 adducts/10(8) deoxyribonucleotide phosphate (dNp).
      Moreover, the DNA adduct levels in these tissues correlated with their NAT1
      dependent PABA activities (r = 0.52; P < 0.01) but not with their OAT activities.
      Statistical and probit analyses indicated that this NAT1 activity was not
      normally distributed and appeared bimodal. Applying the NAT1:OAT activity ratios
      (N:O ratio) allowed arbitrary designation of rapid and slow NAT1 phenotypes, with
      a cutpoint near the median value. Within each of these subgroups, NAT1 correlated
      with OAT (P < 0.05); DNA adduct levels were elevated 2-fold in individuals with
      the rapid NAT1 or NAT1/OAT phenotype. Examination of DNA sequence polymorphisms
      in the NAT1 gene by PCR have demonstrated that an NAT1 polyadenylation
      polymorphism is associated with differences in tissue NAT1 enzyme activity;
      accordingly, NAT1 activity in the bladder of individuals with the heterozygous
      NAT1*10 allele was 2-fold higher than in subjects homozygous for the putative
      wild-type NAT1*4 allele. Likewise, DNA adduct levels in the mucosa of the urinary
      bladder were found to be 2-fold (P < 0.05) higher in individuals with the
      heterozygous NAT1*10 allele (3.5 +/- 2.1 adducts/10(8) dNp) as compared to NAT1*4
      homozygous (1.8 +/- 1.9 adducts/10(8) dNp). Thus, these data provide strong
      support for the hypothesis that NAT1 activity in the urinary bladder mucosa
      represents a major bioactivation step that converts urinary N-hydroxy arylamines
      to reactive N-acetoxy esters that form covalent DNA adducts.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7585582
TI  - Dose-dependent promotion effects of potassium chloride on glandular stomach
      carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine
      and the synergistic influence with sodium chloride.
AB  - The modifying effects of potassium chloride (KCl) ingestion on glandular stomach
      carcinogenesis were investigated in male Wistar rats induced by N-methyl-N'-nitro
      N-nitrosoguanidine (MNNG) and were compared with those of sodium chloride (NaCl).
      A total of 120 male 6-week-old Wistar rats were divided into six groups, each
      consisting of 20 animals. After initiation of treatment with a MNNG solution (100
      parts/million) as their drinking water for 10 weeks, rats were fed a diet
      supplemented with 5% NaCl, 2.5% NaCl, 2.5% NaCl plus 2.5% KCl, 5% KCl, 2.5% KCl,
      or a basal diet alone for the following 62 weeks. Under this experimental
      condition, there were no statistical differences in the final body weights
      between groups. The incidences of adenocarcinomas in the glandular stomachs were
      significantly higher in the 5% NaCl and combined 2.5% NaCl-plus-2.5% KCl groups
      (P < 0.05 and 0.01) than in the MNNG alone (control) group. The incidences of
      atypical or precancerous hyperplasias in the glandular stomachs were increased
      significantly by the 5% NaCl, 2.5% NaCl-plus-2.5% KCl, and 5% KCl treatments (P <
      0.05 or 0.01). The multiplicities of adenocarcinomas were significantly greater
      in the 5% NaCl, 2.5% NaCl, and combined NaCl-plus-KCl groups (P < 0.05 or 0.01)
      compared with the control value. The multiplicity data for atypical hyperplasias
      were most striking; namely, their multiplicities were increased significantly by
      the treatments of NaCl or KCl (P , 0.01) in a clear dose-dependent manner and
      enhanced synergistically by the combined treatment of NaCl and KCl. Because the
      concentrations of KCl used in this study were about 1.3 times lower than those of
      NaCl on a molar basis, although the doses of each chemical were exactly the same
      on a weight-percent basis, it is suggested that the enhancing effects of KCl
      might not be much different from those of NaCl. The results in the present study
      thus indicate that, similarly to NaCl, KCl ingestion exerts dose-dependent
      promoting effects and a synergistic influence with NaCl when given during the
      postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

PMID- 7585583
TI  - Ras-transduced diethylnitrosamine-treated hepatocytes develop into cancers of
      mixed phenotype in vivo.
AB  - The cell of origin of hepatocellular carcinoma (HCC) is controversial. A method
      for marking cells of different lineages in vivo and then determining their
      carcinogenic potential should resolve this issue. A retroviral vector expressing
      activated ras and beta-gal genes (Ras-gal) was transferred into adult rat
      hepatocytes in vivo, and some animals were treated with diethylnitrosamine (DEN).
      Bile ductule cells and the putative stem cells of the liver (the oval cells) did
      not appear to be transduced by this method. At 1 month after transfer, 5-bromo-4
      chloro-3-indolyl-beta-D-galactopyranoside staining was performed on transduced
      rat livers to determine the blue cluster size. Eight % of the clusters in Ras-gal
      transduced, DEN-treated livers contained at least twice as many cells as the
      largest cluster in Ras-gal-transduced, DEN-untreated rats, demonstrating that
      they had acquired markedly abnormal growth properties. When the retroviral vector
      containing beta-gal without ras (Gal-509) was transferred into DEN-treated rats,
      2.5% of the cells were present in clusters containing at least twice as many
      cells as the largest cluster in Gal-509-transduced, DEN-untreated animals. Thus,
      p21-ras may increase the percentage of cells that acquire mutations in response
      to DEN, or it may behave synergistically with other mutations to increase the
      replication rate of cells. Occasional foci in Ras-gal-transduced, DEN-treated
      rats had extramedullary hematopoiesis. Forty % of the Ras-gal-transduced, DEN
      treated rats developed unifocal HCC, mixed HCC/cholangiocarcinoma (CC), or CC at
      3-6 months after transduction, suggesting that hepatocytes can develop into HCC
      or CC if sufficient genetic alterations occur.

PMID- 7585585
TI  - Mechanism of action of chemoprotective ursodeoxycholate in the azoxymethane model
      of rat colonic carcinogenesis: potential roles of protein kinase C-alpha, -beta
      II, and -zeta.
AB  - Several lines of evidence from our laboratory and others indicate that epigenetic
      alterations in protein kinase C (PKC) are involved in colonic carcinogenesis in
      both man and experimental animals. Furthermore, bile salts, known activators of
      PKC, have also been implicated in colonic tumor development. Recently, however,
      our laboratory has demonstrated that, whereas dietary cholic acid increased the
      occurrence of azoxymethane (AOM)-induced rat colonic tumors, ursodeoxycholic acid
      was associated with a significant protective effect. In the present studies, we
      therefore examined changes in PKC isoforms that accompanied AOM-induced tumor
      formation and investigated whether the chemopromotional and/or chemopreventional
      actions of these supplemental dietary bile salts involved changes in specific
      isoforms of PKC. Rats treated with vehicle (saline) or AOM and maintained on bile
      salt unsupplemented or supplemented diets were used to isolate control
      colonocytes and carcinogen-induced tumors, which were then subjected to
      subcellular fractionation. The homogenates and subcellular fractions were then
      probed for individual PKC isoforms by quantitative Western blotting using isoform
      specific antibodies. Normal rat colonocytes expressed PKC-alpha, -beta II, 
      delta, -epilson, and -zeta. AOM, in unsupplemented or cholate-supplemented
      groups, caused significant down-regulation of PKC-alpha, -delta and -zeta and up
      regulation of PKC-beta II, while increasing particulate PKC-alpha, -beta II, and 
      zeta in carcinogen-induced tumors compared to normal colonocytes. Dietary
      supplementation with ursodeoxycholic acid, in marked contrast to these groups,
      prevented the changes in the subcellular distributions of PKC-alpha, -beta II,
      and -zeta, and preserved the expression of PKC-zeta in AOM-induced tumors. These
      studies suggest that changes in specific isoforms of PKC (particularly, PKC
      alpha, -beta II, -delta, and/or -zeta) are involved in colonic malignant
      transformation in the AOM model but do not account for the chemopromotional
      actions of cholic acid in this model. Furthermore, the ability of ursodeoxycholic
      acid to block AOM-induced increases in particulate PKC-alpha, -beta II, and 
      zeta, and/or inhibit down-regulation of PKC-zeta, may contribute to the
      chemopreventive effects of this bile acid.

PMID- 7585586
TI  - Renal tubular tumors and atypical hyperplasias in B6C3F1 mice exposed to lead
      acetate during gestation and lactation occur with minimal chronic nephropathy.
AB  - Lead is a high-priority hazardous substance in humans and a renal carcinogen in
      adult rodents. This study assessed the carcinogenic potential and toxicity of
      gestational and lactational lead exposure in (C57BL/6NCr x C3H/HeN)F1 (hereafter
      called B6C3F1) mice. Effects of a renal tumor promoter [barbital sodium (BB)] on
      lead-initiated lesions were also studied. Pregnant female C57BL/6NCr mice (10
      15/group) previously bred with C3H/HeN males were given lead acetate (0, 500, 750
      and 1000 ppm lead) ad libitum in their drinking water, starting on gestation day
      12 and continuing to 4 weeks postpartum. Offspring were then weaned and divided
      into same-sex groups of 23-25 and observed for a maximum of 112 weeks. Other
      groups received lead and then continuous BB (500 ppm) ad libitum in their
      drinking water from weaning onward. In control male offspring (0 lead/0 BB),
      renal proliferative lesions [(RPLs); defined as atypical tubular hyperplasia or
      tumor] occurred rarely (1 lesion-bearing mouse/23 mice examined, 4%) and did not
      include tumors. RPLs increased in a dose-related fashion with lead exposure (500
      lead/0 BB, 4/25, 16%; 750 lead/0 BB, 6/25, 24%; 1000 lead/0 BB, 12/25, 48%) in
      male offspring and were often multiple. All lead-treated groups had renal tumors,
      including carcinoma, but these were most common at the highest dose (1000 lead/0
      BB, 5/25). Lead-induced renal tumors arose in the absence of the extensive
      chronic nephropathy and lead inclusion bodies typically seen with lead
      carcinogenesis in rodents exposed chronically as adults. Postnatal BB exposure
      had no effect on RPL incidence (e.g., 1000 lead/500 BB, 8/25, 32%). Lead-treated
      female offspring also developed RPLs, including adenoma and carcinoma, but at a
      much lower rate than males. Thus, short-term lead exposure during the
      gestational/lactational period has carcinogenic potential in the mouse kidney.

PMID- 7585584
TI  - Comparative carcinogenic effects of nickel subsulfide, nickel oxide, or nickel
      sulfate hexahydrate chronic exposures in the lung.
AB  - The relative toxicity and carcinogenicity of nickel sulfate hexahydrate
      (NiSO4.6H2O), nickel subsulfide (Ni3S2), and nickel oxide (NiO) were studied in
      F344/N rats and B6C3F1 mice after inhalation exposure for 6 h/day, 5 days/week
      for 2 years. Nickel subsulfide (0.15 and 1 mg/m3) and nickel oxide (1.25 and 2.5
      mg/m3) caused an exposure-related increased incidence of alveolar/bronchiolar
      neoplasms and adrenal medulla neoplasms in male and female rats. Nickel oxide
      caused an equivocal exposure-related increase in alveolar/bronchiolar neoplasms
      in female mice. No exposure-related neoplastic responses occurred in rats or mice
      exposed to nickel sulfate or in mice exposed to nickel subsulfide. These findings
      are consistent with results from other studies, which show that nickel subsulfide
      and nickel oxide reach the nucleus in greater amounts than the do water-soluble
      nickel compounds such as nickel sulfate. It has been proposed that the more water
      insoluble particles are phagocytized, whereas the vacuoles containing nickel
      migrate to the nuclear membrane, where they release nickel ions that effect DNA
      damage. The findings from these experimental studies show that chronic exposure
      to nickel can cause lung neoplasms in rats, and that this response is related to
      exposure to specific types of nickel compounds.

PMID- 7585589
TI  - Adenovirus-mediated gene therapy of hepatocellular carcinoma using cancer
      specific gene expression.
AB  - Most patients with hepatocellular carcinoma have an elevated alpha-feto-protein
      (AFP) level. This high level of AFP expression is transcriptionally controlled by
      the 5'-flanking sequence of the AFP gene. Using the 5'-flanking sequence as a
      promoter for the herpes simplex virus thymidine kinase (HSV-TK) gene in an
      adenoviral vector (Av1AFPTK1), the therapeutic efficacy of adenovirus-mediated
      HSV-TK gene transduction, followed by ganciclovir (GCV) administration, was
      studied in tumors in athymic nude mice. Av1AFPTK1 transduction of two cell lines
      demonstrated HSV-TK enzyme activity only in the AFP-producing cells (HuH7) and
      not in the AFP nonproducing cells (SK-Hep-1). As expected, only transduced HuH7
      cells were killed by GCV treatment. Transduction by an adenoviral vector
      harboring a Rous sarcoma virus promoter and HSV-TK gene (Av1TK1) showed enzymatic
      activity and GCV killing in both cell lines. All HuH7 tumors that were transduced
      with either Av1AFPTK1 or Av1TK1 completely regressed after GCV treatment. On the
      other hand, there was complete regression of SK-Hep-1 tumors only when treated
      with Av1TK1 and GCV and not when treated with Av1AFPTK1 and GCV. Thus, cell
      specific killing was achieved by adenoviral vector containing AFP promoter for
      the HSV-TK gene and GCV treatment.

PMID- 7585587
TI  - Relaxin activates the L-arginine-nitric oxide pathway in human breast cancer
      cells.
AB  - Recently, we demonstrated that relaxin (RLX), a peptide hormone of ovarian
      origin, inhibits growth and promotes differentiation of MCF-7 breast
      adenocarcinoma cells. We also showed that RLX stimulates the production of nitric
      oxide (NO) in several cell types. NO has been reported to have antitumor activity
      by inhibiting proliferation, promoting differentiation, and reducing the
      metastatic spread of some tumor cell types. In this study, we aimed at evaluating
      whether RLX influences the L-arginine-NO pathway in MCF-7 cells. The cells were
      grown in the absence or presence of RLX at different concentrations, and cell
      proliferation, constitutive and inducible NO synthase activities, nitrite
      production, and intracellular levels of cyclic GMP were investigated. The results
      obtained indicate that RLX increases inducible NO synthase activity and
      potentiates NO production. This was accompanied by an elevation of intracellular
      cyclic GMP, which is known to mediate the cell response to NO. The RLX-induced
      activation of the L-arginine-NO pathway in the MCF-7 cells was inversely related
      to the rate of cell proliferation. These results suggest that the cytostatic
      effect of RLX on MCF-7 breast cancer cells may rely on its ability to stimulate
      endogenous production of NO.

PMID- 7585588
TI  - Chemosensitivity testing of human tumors using a microplate adenosine
      triphosphate luminescence assay: clinical correlation for cisplatin resistance of
      ovarian carcinoma.
AB  - An ATP luminescence assay (TCA 100) was used to measure chemotherapeutic drug
      sensitivity and resistance of dissociated tumor cells cultured for 6 days in
      serum-free medium and 96-well polypropylene microplates. Studies were performed
      with surgical, needle biopsy, pleural, or ascitic fluid specimens using 10,000
      20,000 cells/well. ATP measurements were used to determine tumor growth
      inhibition. Single agent and drug combinations were evaluated using the area
      under the curve and 50% inhibitory concentration (IC50) results for a series of
      test drug concentrations. The ATP luminometry method had high sensitivity,
      linearity, and precision for measuring the activity of single agents and drug
      combinations. Assay reproducibility was high with intraassay and interassay
      coefficients of variation of 10-15% for percentage of tumor growth inhibition, 5
      10% for area under curve, and 15-20% for IC50 results. Good correlation (r =
      0.93) between the area under the curve, and IC50 results was observed.
      Cytological studies with 124 specimens demonstrated selective growth of malignant
      cells in the serum-free culture system. Studies with malignant and benign
      specimens also showed selective growth of malignant cells in the serum-free
      medium used for assay. The assay had a success rate of 87% based on criteria for
      specimen histopathology, magnitude of cell growth, and dose-response drug
      activity. Cisplatin results for ovarian carcinoma are presented for 81 specimens
      from 70 untreated patients and 33 specimens from 30 refractory patients. A model
      for interpretation of these results based on the correlation of clinical response
      with the area under the curve and IC50 results indicates that the assay has > 90%
      accuracy for cisplatin resistance of ovarian carcinoma. Additional studies are in
      progress to evaluate the clinical efficacy of this assay.

PMID- 7585590
TI  - Lysine reduces renal accumulation of radioactivity associated with injection of
      the [177Lu]alpha-[2-(4-aminophenyl) ethyl]-1,4,7,10-tetraaza-cyclodecane-1,4,7,10
      tetraacetic acid-CC49 Fab radioimmunoconjugate.
AB  - The high uptake and prolonged renal retention of monoclonal antibody fragments
      that are conjugated with radiometal chelates precludes their routine clinical use
      due to high background counts, which may hinder detection of nearby lesions
      and/or cause renal radiotoxicity. We report on the potential use of Lys as a
      pharmacological agent to enhance renal excretion of the [177Lu]alpha-[2-(4
      aminophenyl) ethyl]-1,4,7,10-tetraaza-cyclodecane-1,4,7,10-tetraacetic acid CC49
      Fab ([177Lu]CC49 Fab) radioimmunoconjugate. The monoclonal antibody portion of
      this complex is directed toward the tumor-associated glycoprotein-72 antigen. Lys
      was administered to female BALB/c mice by i.p. injections. [177Lu]CC49 Fab bolus
      injections were given by the i.v. route. Results of our investigations showed
      that: (a) kidney radioactivity concentrations were inversely related to Lys dose.
      The optimal dose (50 mg/mouse) evoked a 3-fold reduction in kidney counts; (b)
      Lys was most effective when injected 15 min before, or at the same time as,
      [177Lu]CC49 Fab; (c) the renal effect was both rapid (3-fold decrease at 15 min
      after injection) and prolonged (4-fold decrease at 24 h after injection); (d) a
      single Lys dose decreased total body radioactivity by > 2.5-fold; (e) urine
      excretion of radioactivity was enhanced in Lys-treated mice. High pressure liquid
      chromatographic analyses using a GF-250 column showed that a large fraction of
      this urine radioactivity coeluted with a [177Lu]CC49 Fab injection standard. We
      conclude that Lys enhances the urinary excretion of radioactivity associated with
      [177Lu]CC49 Fab. These observations warrant further study with regard to the use
      of amino acids or their derivatives as pharmacological agents to enhance the
      urinary excretion of small-molecule radioimmunoconjugates.

PMID- 7585592
TI  - A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage
      dependent and -independent growth of human tumor cell lines.
AB  - Farnesyl protein transferase (FPTase) catalyzes the first of a series of
      posttranslational modifications of Ras required for full biological activity.
      Peptidomimetic inhibitors of FPTase have been designed that selectively block
      farnesylation in vivo and in vitro. These inhibitors prevent Ras processing and
      membrane localization and are effective in reversing the transformed phenotype of
      Rat1-v-ras cells but not that of cells transformed by v-raf or v-mos. We have
      tested the effect of the FPTase inhibitor L-744,832 (FTI) on the anchorage
      dependent and -independent growth of human tumor cell lines. The growth of over
      70% of all tumor cell lines tested was inhibited by 2-20 microM of the FTI,
      whereas the anchorage-dependent growth of nontransformed epithelial cells was
      less sensitive to the effects of the compound. No correlation was observed
      between response to drug and the origin of the tumor cell or whether it contained
      mutationally activated ras. In fact, cell lines with wild-type ras and active
      protein tyrosine kinases in which the transformed phenotype may depend on
      upstream activation of the ras pathway were especially sensitive to the drug. To
      define the important targets of FTI action, the mechanism of cellular drug
      resistance was examined. It was not a function of altered drug accumulation or of
      FPTase insensitivity since, in all cell lines tested, FPTase activity was readily
      inhibited within 1 h of treatment with the inhibitor. Furthermore, the general
      pattern of inhibition of cellular protein farnesylation and the specific
      inhibition of lamin B processing were the same in sensitive and resistant cells.
      In addition, functional activation of Ras was inhibited to the same degree in
      sensitive and resistant cell lines. However, the FTI inhibited the epidermal
      growth factor-induced activation of mitogen-activated protein kinases in
      sensitive cells but not in two resistant cell lines. These data suggest that the
      drug does inhibit ras function and that resistance in some cells is associated
      with the presence of Ras-independent pathways for mitogen-activated protein
      kinase activation by tyrosine kinases. We conclude that FPTase inhibitors are
      potent antitumor agents with activity against many types of human cancer cell
      lines, including those with wild-type ras.

PMID- 7585591
TI  - Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal
      antibody to human vascular endothelial growth factor/vascular permeability
      factor121.
AB  - We elucidated the relationship between vascular endothelial growth
      factor/vascular permeability factor (VEGF/VPF), which is a potent angiogenic
      factor, and the growth of primary and metastatic tumors using an
      immunoneutralizing monoclonal antibody against human VEGF/VPF121. The monoclonal
      antibody, MV303, suppressed the growth of human umbilical vein endothelial cells
      (HUVEC) induced by VEGF/VPF121 or VEGF/VPF165 but did not inhibit its growth
      induced by basic fibroblast growth factor. MV303 inhibited the binding of 125I
      VEGF/VPF121 to HUVEC. We examined the effects of MV303 on tumor angiogenesis
      using a membrane chamber packed with the human fibrosarcoma cell line HT-1080 and
      implanted s.c. into BALB/c mice. The neovascularization induced by HT-1080 was
      inhibited by the i.v. injection of MV303 at a dose of 100 micrograms/mouse.
      Furthermore, the growth of solid tumors of s.c. implanted HT-1080 in BALB/c nude
      mice was almost completely inhibited by the i.v. and s.c. administration of MV303
      ten times from day 1 at a dose of 100 micrograms/mouse (T/C values of tumor
      volume at day 18 were 0.20 and 0.18, respectively). Tumor growth was suppressed
      when MV303 was administered, even from eight days after tumor inoculation. MV303
      suppressed the increase in lung weight caused by experimental metastasis with
      i.v. inoculation of cultured HT-1080 cells to BALB/c nude mice. The life spans of
      the mice treated with MV303 were significantly prolonged. These results indicated
      that VEGF/VPF played an important role in both primary and metastatic tumor
      growth as a tumor angiogenesis factor. MV303, an immunoneutralizing monoclonal
      antibody against VEGF/VPF, potently inhibited both primary and metastatic tumor
      growth with no marked side effects.

PMID- 7585593
TI  - Inhibition of human tumor xenograft growth by treatment with the farnesyl
      transferase inhibitor B956.
AB  - ras oncogenes are present in several types of cancers but are most frequently
      described in colon and pancreatic carcinomas. Consequently, ras is being targeted
      for drug development as a means to develop therapies for these types of cancer.
      The ras protein is posttranslationally modified by the addition of a farnesyl
      group, followed by cleavage of the COOH-terminal 3 amino acids and methylation of
      the prenylated cysteine. Because the posttranslational addition of farnesyl is
      obligatory not only for the remaining modifications to take place but also for
      ras control of cell growth, inhibitors of farnesylation are being developed as
      potential antitumor agents. In this report, a new peptidomimetic inhibitor of
      farnesyl transferase is described. This compound, B956, and its methyl ester
      B1086, inhibit the formation of colonies in soft agar of 14 human tumor cell
      lines expressing different ras oncogenes at concentrations between 0.2 and 60
      microM. Higher concentrations of B956 (10-80 microM) were required to inhibit
      colony formation by 5 tumor cell lines without ras mutations. B956/B1086 at 100
      mg/kg also inhibited tumor growth by EJ-1 human bladder carcinoma, HT1080 human
      fibrosarcoma, and to a lesser extent by HCT116 human colon carcinoma xenografts
      in nude mice. Furthermore, inhibition of tumor growth by B956 is shown to be
      correlated with inhibition of ras posttranslational processing in the tumor.
      Thus, peptidomimetic inhibitors of ras farnesylation have the potential to be
      developed as therapy for ras-dependent tumors.

PMID- 7585594
TI  - Design and analysis of in vitro antitumor pharmacodynamic studies.
AB  - The relationship between drug concentration (C), exposure time (t), and the
      resulting effect (h) for a chemotherapeutic agent is expressed as Cn x t = h. The
      value of n, derived from curve fitting of the C versus t plot, indicates the
      relative importance of concentration and exposure time. The selection of
      concentrations and exposure times in a pharmacodynamic experiment may affect the
      precision and accuracy of parameter estimation. The use of optimal designs is
      even more critical when the numbers of experimental conditions are limited by
      tumor availability (e.g., small size of surgical specimens from patients). The
      present study used computer-simulated data to define the most efficient in vitro
      pharmacodynamic experimental designs and the optimal method of pharmacodynamic
      data analysis. All studies used Monte Carlo simulations to compare designs with
      varying numbers of drug concentrations, exposure times, and replications. For
      each selected design, 50-100 error-containing data sets were created by addition
      of experience-based random errors to expected concentration-response profiles. To
      compare methods of data analysis, the same 1250 simulated data sets were analyzed
      by two methods (i.e., surface response method and traditional method). The
      results showed that simultaneous fitting of drug effect at all concentrations and
      all exposure times by the surface response method yielded n estimates that had
      greater precision and accuracy than a traditional method that required sequential
      determination of the effective inhibitory concentration (e.g., IC50) and then the
      n value using the IC50 at different exposure times. Subsequent studies were
      analyzed using the surface response method. To evaluate the effect of selection
      of concentrations and exposure times on the precision of n estimation, between
      1100 and 2200 simulated data sets, with 400 observations per data set, were
      generated using different exposure times and drug concentrations. Because the
      number of observations was limited to 400, the number of replications at each
      condition varied depending on the total number of selected conditions.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7585597
TI  - In vivo antitumor effects of unconjugated CD30 monoclonal antibodies on human
      anaplastic large-cell lymphoma xenografts.
AB  - CD30 is a M(r) 120,000 surface antigen identified originally by the Ki-1
      monoclonal antibody (moAb) against primary and cultured Reed-Sternberg cells
      present in Hodgkin's disease and anaplastic large-cell lymphomas (ALCLs).
      Examination of two ALCL cell lines (Karpas 299 and Michel) demonstrated cell
      surface expression of CD30. Incubation of these lymphomas with two anti-CD30
      moAbs that recognize the ligand-binding site (M44 or HeFi-1) resulted in
      significant growth inhibition in vitro, with significant decreases in cell
      viability. Another anti-CD30 moAb, Ber-H2, which recognizes a determinant not
      involved in ligand binding, had no effect on ALCL growth in vitro. When these
      human ALCL lines were transferred i.v. into mice with severe combined immune
      deficiency, the mice developed extensive metastasis in the s.c., brain, or eye
      tissues. The treatment of mice with either M44 or HeFi-1 anti-CD30 moAbs resulted
      in significant increases in survival, with some mice remaining disease free for
      more than 100 days. Thus, anti-CD30 treatment is efficacious for CD30+ ALCL cell
      lines in vivo, and unconjugated anti-CD30 moAbs may be of potential clinical use.

PMID- 7585595
TI  - Biodistribution of 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv
      fragments in nude mice with interleukin 2 alpha receptor-positive tumor
      xenografts.
AB  - We evaluated the biodistribution, pharmacokinetics, and generation of catabolites
      of an 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragment (dsFv) in
      tumor-bearing nude mice. This dsFv is genetically engineered from a murine
      monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2
      alpha) receptor. Labeling was performed with 18F using N-succinimidyl 4
      ([18F]fluoromethyl)benzoate or with 125I using the Iodo-Gen method. The
      immunoreactivities of the radiolabeled anti-Tac dsFv were > 82%. The
      biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude
      mice (approximately five/group) bearing s.c. tumor xenografts. Cell line A431
      served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line
      served as our IL-2 receptor-positive tumor. Animals received injections of 18F
      labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 micrograms) and 125I-labeled
      anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 microgram). Blood clearance for both
      preparations was rapid, with < 10% retained in the blood by 15 min. Maximum
      accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean
      of 4.2% injected dose/g (18F) and 5.6% of injected dose/g (125I). At 6 h, the
      ATAC4 tumors contained 11 times more 18F and 3 times more 125I than did the A431
      tumors. The ATAC4 tumor:blood ratios for the 18F and 125I were > 12:1 and > 1.4:1
      at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were
      less than 1. The kidneys were the major route of elimination. Catabolites
      appeared quickly and were identified as [125I]iodide and predominantly N-epsilon
      [18F]4-fluoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to
      evaluate the biodistribution of an 18F-labeled Fv fragment in vitro and in vivo.
      In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine
      containing catabolites for 18F-labeled dsFv and [125I]iodide for 125I-labeled
      dsFv.

PMID- 7585596
TI  - Generation of antimelanoma cytotoxic T lymphocytes from healthy donors after
      presentation of melanoma-associated antigen-derived epitopes by dendritic cells
      in vitro.
AB  - MHC class I-restricted CTLs specific for antigens expressed by malignant cells
      are an important component of immune responses against human cancer. Recently, in
      melanoma a number of melanocyte differentiation antigens have been identified as
      potential tumor rejection antigens. In the present study, we show that by
      applying peptide-loaded dendritic cells, induced by granulocyte-macrophage colony
      stimulating factor and interleukin 4 from peripheral blood monocytes of healthy
      donors, we were able to elicit melanoma-associated antigen-specific CTL in vitro.
      We demonstrate the induction of CTLs directed against HLA-A2.1 presented epitopes
      derived from tyrosinase, gp100, and Melan A/MART-1. Apart from lysis of peptide
      loaded target cells, these CTLs displayed reactivity with HLA-A2.1+ melanoma
      tumor cell lines and cultured normal melanocytes endogenously expressing the
      target antigen. These data indicate that these CTLs recognize naturally processed
      and presented epitopes and that precursor CTLs against melanocyte differentiation
      antigens are present in healthy individuals. The ability to generate tumor
      specific CTLs in vitro, using granulocyte-macrophage colony-stimulating
      factor/interleukin 4-induced dendritic cells, illustrates the potential use of
      this type of antigen-presenting cells for vaccination protocols in human cancer.

PMID- 7585600
TI  - Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women
      in Hong Kong.
AB  - Accumulating evidence suggests that the p53 gene is a good target for molecular
      epidemiological studies to search for risk factors in carcinogenic events. The
      lung cancer incidence for females in Hong Kong is unusually high, ranking among
      the highest in the world despite a low percentage with a history of smoking. To
      gain insights into possible etiological risk factors responsible for this high
      incidence, we examined p53 mutations in 35 lung cancer specimens from Chinese
      females living in Hong Kong and compared them with 35 matched cases from Japanese
      women as well as previously reported p53 mutations in the world literature. p53
      mutations in exons 5-8 were present in 20 and 31% of the Hong Kong and Japanese
      cases, respectively. Notably, single-base deletions within runs of identical
      bases were observed in 3 (43%) of the 7 mutations in the Hong Kong cases, in
      contrast to the absence of such mutations in the controls and the extreme
      scarcity in the literature, suggesting that distinct environmental and/or genetic
      factor(s) might be involved. Although the frequent occurrence of characteristic
      single-base deletions could be a reflection of mutator mutations leading to
      inefficient mismatch repair of slipped strand mispairings, none of the lung
      cancer specimens exhibited such microsatellite instabilities.

PMID- 7585598
TI  - Expression of multidrug resistance-associated protein in NIH/3T3 cells confers
      multidrug resistance associated with increased drug efflux and altered
      intracellular drug distribution.
AB  - Multidrug resistance is a major obstacle to cancer treatment. Using an expression
      cDNA library transfer approach to elucidating the molecular basis of non-P
      glycoprotein-mediated multidrug resistance, we previously established that
      expression of multidrug resistance protein (MRP), an ATP-binding cassette
      superfamily transporter, confers multidrug resistance (G. D. Kruh et al., Cancer
      Res., 54: 1649-1652, 1994). In the present study, we generated NIH/3T3 MRP
      transfectants without using chemotherapeutic drugs to facilitate the
      pharmacological analysis of the MRP phenotype. MRP transfectants displayed
      increased resistance to several lipophilic drugs, including doxorubicin,
      daunorubicin, etoposide, actinomycin D, vincristine, and vinblastine. However,
      increased resistance was not observed for Taxol, a drug for which transfection of
      MDR1 confers high levels of resistance. Verapamil increased the sensitivity of
      MRP transfectants relative to control transfectants, but reversal was incomplete
      for doxorubicin and etoposide, the drugs for which MRP conferred the highest
      resistance levels. For the latter two drugs, MRP transfectants, which were
      approximately 8- and approximately 10-fold more sensitive than control cells in
      the absence of verapamil, exhibited 3.8- and 3.3-fold relative sensitization with
      10 microM verapamil, respectively, but remained approximately 2 and approximately
      3-fold more resistant than control cells. Analysis of drug kinetics using
      radiolabeled daunorubicin revealed decreased accumulation and increased efflux in
      MRP transfectants. Confocal microscopic analysis of intracellular daunorubicin in
      MRP transfectants was consistent with reduced intracellular drug concentrations,
      and also revealed an altered pattern of intracellular drug distribution
      characterized by the initial accumulation of drug in a perinuclear location,
      followed by the development of a punctate pattern of drug scattered throughout
      the cytoplasm. This pattern was suggestive of a process of drug sequestration,
      possibly followed by vesicle transport. Both increased drug efflux and
      perinuclear drug accumulation are consistent with the reported localization of
      MRP in plasma and cytosolic membranes (N. Krishnamachary and M. S. Center, Cancer
      Res., 53: 3658-3663, 1993; M. J. Flens et al., Cancer Res., 54: 4557-4563, 1994).
      These results thus indicate that the drug specificity of MRP is quite similar to
      that of MDR1, but also suggest potential differences in Taxol specificity and the
      level of verapamil sensitivity. In addition, these results indicate that MRP
      functions to extrude drug from the cell, but additionally suggest the intriguing
      possibility that drug sequestration contributes to drug resistance by protecting
      cellular targets and/or contributing to drug efflux.

PMID- 7585599
TI  - Loss of heterozygosity at the familial RCC t(3;8) locus in most clear cell renal
      carcinomas.
AB  - Previously, we had observed that more than 80% of clear cell renal carcinomas
      (RCCs) exhibited loss of heterozygosity (LOH) between the microsatellite markers
      D3S1285 (in 3p14.1) and D3S1295 (in 3p21.1), a region which includes the protein
      tyrosine phosphatase gamma locus (PTPRG locus, PTP gamma gene) and the 3p14.2
      break of the familial RCC-associated translocation, t(3;8)(p14.2;q24), which has
      been hypothesized to affect expression of an RCC suppressor gene or oncogene.
      Using seven microsatellite markers and four markers derived from a PTPRG YAC
      contig, we have further delineated the 3p14.2 region of LOH in RCCs. Eighty-nine
      % of clear cell RCCs (31 of 35) showed a common region of loss between the
      D3S1481 and D3S1312 loci which flank the 3p14.2 t(3;8) translocation breakpoint
      and the PTP gamma gene. The PTP gamma gene occupies approximately 780 kilobase
      pairs between markers D3S1480 and D3S1312, with its currently defined 5' end
      greater than 200 kilobase pairs centromeric to the 3p14.2 translocation break.
      Although most of the RCCs with LOH between D3S1481 and D3S1312 loci have lost at
      least a portion of one PTP gamma allele, we have tested all known exons of the
      remaining PTP gamma gene in a number of the kidney tumors and have not observed
      mutations. Thus, there may be another gene in the vicinity of the 3p14.2 break
      that is important not only in the familial RCCs in the t(3;8) family but in the
      majority of clear cell RCCs.

PMID- 7585601
TI  - Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered
      epidermal growth factor receptor activity.
AB  - Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected
      NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These
      cells, designated as NODC-2 cells, acquire proliferative properties associated
      with tumorigenic transformation such as loss of contact inhibition, decreased
      population doubling time, anchorage-independent growth, and tumor production in
      nude mice. At least one of these parameters, loss of contact inhibition, remains
      dependent on elevated ODC levels. We have used these cells to investigate the
      molecular mechanisms by which ODC overexpression drives cell transformation and
      to examine the involvement of other proto-oncogene products in this process. An
      interaction between ODC overexpression and the epidermal growth factor receptor
      (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand
      induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to
      similarly treated control NLK cells. Disruption of EGF-R mediated signal
      transduction in NODC-2 cells both by treatment with tyrphostin-25 or by
      transfection with a vector expressing a dominant negative EGF-R mutant resulted
      in reacquisition of contact-inhibited growth and suppression of anchorage
      independent, clonogenic growth in soft agar. We conclude that ODC-induced
      transformation of NIH/3T3 cells is mediated, at least partly, by alterations in
      EGF-R signal transduction activity.

PMID- 7585602
TI  - The 1p deletion is not a reliable marker for the prognosis of patients with
      neuroblastoma.
AB  - Human neuroblastoma cells often have deletions of the distal short arm of
      chromosome 1 (1p). Earlier studies using chromosome analysis had suggested that
      the 1p deletion is correlated with a poor survival chance for the patient. We
      have reevaluated this possibility by analyzing 51 neuroblastomas for loss of
      heterozygosity (LOH) at 1p. We detected LOH in 32% of the cases. LOH did not
      correlate with the age of the patients at diagnosis or with tumor stage but was
      correlated significantly with amplification of the MYCN proto-oncogene. Nine of
      10 MYCN-amplified tumors had deletions in 1p (P < 0.001). Survival chances of
      patients with tumors carrying MYCN amplification together with the deletion at 1p
      were decreased significantly (eight of nine affected patients died) compared with
      a patient group without any of these aberrations (P < 0.001). However, the
      deletion of 1p alone without MYCN amplification was not associated with a poor
      outcome compared with patients who had neither deletion nor amplification (only
      two of eight affected patients died; P = 0.803). From these data we conclude that
      1p deletions are not reliable markers to determine a patient's prognosis. They
      may, however, identify a subgroup of neuroblastomas in which MYCN is amplified
      readily, resulting in rapid tumor progression.

PMID- 7585603
TI  - Suppression of rat glutathione transferase P expression by peroxisome
      proliferators: interaction between Jun and peroxisome proliferator-activated
      receptor alpha.
AB  - Glutathione transferase-P (GST-P) in rats is specifically expressed in
      precancerous lesions and in hepatomas induced by carcinogens or spontaneously
      arising hepatomas. GST-P expression in preneoplastic lesions is suppressed by
      peroxisome proliferators. To determine the mechanism of suppression of GST-P
      expression by peroxisome proliferators on a molecular level, we have analyzed the
      effects of peroxisome proliferators and their receptor (peroxisome proliferator
      activated receptor alpha, PPAR alpha) on GST-P expression. GST-P gene expression
      linked to a reporter gene was specifically suppressed by cotransfection with a
      PPAR alpha expression plasmid in the presence of the peroxisome proliferator,
      clofibrate. The target element of the suppression was a 12-O-tetradecanoylphorbol
      13-acetate-responsive element located 61 nucleotides upstream from the cap site,
      which is also internal to a Maf consensus binding sequence. Both Jun and Maf bind
      to this element and activate the gene having this element, but only Jun-activated
      expression was specifically inhibited by PPAR alpha. Expression of a transfected
      reporter gene linked to a PPAR-responsive element was inhibited by cotransfection
      with a Jun expression plasmid. These results suggest that PPAR alpha and Jun
      interact and share inhibitory activities, similar to Jun and the glucocorticoid
      receptor.

PMID- 7585604
TI  - Allelotype analysis of childhood acute lymphoblastic leukemia.
AB  - To identify the genetic events that may play an important role in leukemogenesis
      of childhood ALL, we report for the first time the allelotyping of childhood ALL.
      Twenty-four cases of childhood ALL were screened for loss of heterozygosity (LOH)
      using 101 highly polymorphic microsatellite markers, which are distributed among
      all autosomal chromosomes. For LOH analysis on both chromosomes 9 and 12, 54
      childhood ALL samples were examined. The most frequent allelic loss was found on
      chromosomal arm 9p, where 20 of 50 (40%) informative samples showed LOH.
      Moreover, nearly 30% of samples that did not have either homozygous deletions or
      point mutations of the putative tumor suppressor genes CDKN2/INK4A/p16 and
      INK4B/p15 on chromosomal arm 9p had LOH at D9S171. Loss of chromosomal arm 12p
      was also frequent (26%). Mutational analysis suggested that the altered gene on
      12p is not the cyclin-dependent kinase inhibitor p27/Kip1, which is also on 12p.
      Several other regions that had LOH included 1p, 4q, 5p, 6q, 7p, 8p, 9q, 10q, 13q,
      17p, 17q, 18q, 19q, and 22q. Of 24 patients, 19 (79%) showed allelic loss on at
      least one chromosomal arm. Samples of two patients (8%) showed LOH on almost all
      chromosomes. Fractional allelic loss, calculated for each sample as the total
      number of chromosomal arms lost/total number of arms with information, showed a
      median value of 0.04 and a mean of 0.123 (range, 0 to 0.95). This fractional
      allelic loss is lower than those reported for many solid tumors. This analysis
      shows the extreme power of LOH analysis using microsatellite markers in childhood
      ALL.

PMID- 7585606
TI  - Regulation of the proto-oncogenes bcl-2 and c-myc by the Wilms' tumor suppressor
      gene WT1.
AB  - The Wilms' tumor gene WT1 functions as a tumor suppressor gene, repressing
      transcription of several growth factors and growth factor receptors. The bcl-2
      and c-myc proto-oncogenes are essential for regulation of apoptosis and cell
      proliferation with roles in development and oncogenesis. We found that WT1 can
      repress transcription of both the bcl-2 and c-myc promoters. This suggests that
      WT1 regulates bcl-2 and c-myc during renal development, and the loss of
      functional WT1 results in deregulation of bcl-2 and c-myc, contributing to tumor
      formation.

PMID- 7585605
TI  - Terminal deletion of chromosome 3p sequences in nonpapillary renal cell
      carcinomas: a breakpoint cluster between loci D3S1285 and D3S1603.
AB  - Deletion of chromosome 3p13-pter sequences is a specific genetic change in
      nonpapillary renal cell carcinomas (RCC). The VHL gene, a putative tumor
      suppressor gene, has already been cloned from the 3p25-26 chromosomal region.
      Conflicting cytogenetic and RFLP studies, however, suggest multiple interstitial
      deletions and additional tumor suppressor genes at chromosome 3p. To investigate
      the loss of DNA sequences on chromosome 3p in nonpapillary RCCs, we analyzed 41
      paired normal and tumor DNAs obtained from short-term cultures of pure tumor
      cells with 12 polymorphic microsatellite markers covering the 3p11.2-p25 region.
      Deletion mapping provided evidence for terminal deletion with the most distal
      breakpoint between D3S1300 and D3S1285 loci, which is the site of breakpoint in
      familial 3;8 translocation predisposing to nonpapillary RCC. All breakpoints,
      including those occurring in familial translocation 3;6, were clustered in a more
      than 20-cM-large region between loci D3S1285 and D3S1603. Interestingly, 7 of the
      28 cases with 3p deletion showed a recurrent breakpoint between D3S1603 and
      D3S1595, which cover about 1 cM genetic distance. The results suggest that a
      tumor suppressor gene, in addition to the VHL gene, might be localized somewhere
      on chromosome 3p distal to the familial 3;8 translocation, or it might be at the
      breakpoint cluster. Alternatively, the breakpoint serves as a mechanism to lose
      distal DNA sequences.

PMID- 7585608
TI  - Distinct regions of allelic loss on chromosome 4 in human primary bladder
      carcinoma.
AB  - Accumulating evidence implicates the presence of putative tumor suppressor genes
      on human chromosome 4 that are potentially inactivated in the genesis of several
      different neoplasms. To accurately determine the frequency of allelic loss on
      both arms of human chromosome 4, we screened 282 fresh-frozen human bladder
      carcinomas for allelic loss. Loss of heterozygosity of at least one marker for
      chromosome 4 was identified in 129 tumors (45.7%). Fine mapping was accomplished
      using up to 15 polymorphic markers on the p arm and 19 markers on the q arm. We
      identified a 3-cM minimal area of loss on the p arm between microsatellite
      markers D4S1608 and D4S404 deleted in 82 tumors (29%). A total of 68 tumors (24%)
      targeted a 14-cM critical region identified on the distal q arm between markers
      D4S426 and D4S408. Loss of these two regions correlated with advanced stage and
      grade of the lesions. These data identify distinct regions of loss on chromosome
      4 potentially involved in the late progression of bladder carcinoma.

PMID- 7585610
TI  - Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma
      detected by fluorescence in situ hybridization.
AB  - The pathogenetic relationship between high-grade prostatic intraepithelial
      neoplasia (PIN), prostatic carcinoma, and metastases is poorly understood. We
      used fluorescence in situ hybridization (FISH) with centromere-specific probes
      for chromosomes 7, 8, 10, 12, and Y to evaluate numeric chromosomal anomalies in
      PIN (68 foci), localized prostatic carcinoma (78 foci), and lymph node metastases
      (8 foci) in 40 whole-mount radical prostatectomy and pelvic lymphadenectomy
      specimens. Chromosomal anomalies were found in 50, 51, and 100% of the foci of
      PIN, carcinoma, and metastases, respectively. The mean numbers of abnormal
      chromosomes per focus were 0.66 in PIN, 1.09 in carcinoma, and 3.75 in
      metastases. The most frequent anomaly in PIN was a gain of chromosome 8 (32% of
      foci), followed by gains of chromosomes 10 (13%), 7 (10%), 12 (4%), and Y (4%).
      The most frequent anomalies in foci of carcinoma were gains of chromosomes 7 and
      8 (28% and 30% of foci, respectively), followed by gains of chromosomes 10 (23%),
      12 (9%), and Y (9%). There was a positive correlation of the gain of chromosome 8
      with the pathological stage and Gleason score (both P < 0.05). Usually, carcinoma
      foci contained more anomalies than paired PIN foci, but five prostates contained
      one or more foci of PIN with more anomalies than carcinoma. Among the cases with
      metastases, usually one or more foci of the primary tumor shared chromosomal
      anomalies with the matched metastases. Our results indicate that PIN and
      prostatic carcinoma foci have similar proportions of chromosomal anomalies, but
      foci of carcinoma usually have more alterations. This observation supports the
      hypothesis that PIN is often a precursor of carcinoma, although there are some
      carcinoma foci that have few or no apparent chromosomal alterations, whereas
      concurrent PIN foci have multiple alterations. A gain of chromosome 8 was the
      most common numerical alteration and was associated with increasing cancer stage
      and grade, suggesting that it may play a role in the initiation and progression
      of prostatic carcinoma. Usually, one or more foci of the primary tumor shared
      chromosomal anomalies with associated lymph node metastases, suggesting that,
      often, just a single focus of carcinoma gives rise to metastases.

PMID- 7585607
TI  - Evidence for three tumor suppressor gene loci on chromosome 8p in human prostate
      cancer.
AB  - Allelic loss of human chromosome sequences is often equated with inactivation of
      putative tumor suppressor genes. Loss of sequences on the short arm of chromosome
      8 (8p) has been observed in human cancers, especially of 8p22 in prostate tumors.
      By using PCR analysis of highly polymorphic microsatellite repeat markers at nine
      8p loci in 135 tumors, we observed deletion of sequences at 8p22 and at two other
      proximal deletion domains. These novel deletion domains encompass the NEFL locus
      and D8S87-ANK1 loci, respectively. These data suggest that three 8p tumor
      suppressor gene loci may be independently deleted in human prostate cancers.

PMID- 7585611
TI  - Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast
      tumors reveals different patterns of chromosomal gains and losses in
      fibroadenomas and diploid and aneuploid carcinomas.
AB  - Comparative genomic hybridization serves as a screening test for regions of copy
      number changes in tumor genomes. We have applied the technique to map DNA gains
      and losses in 33 cases of formalin-fixed, paraffin-embedded primary breast tumors
      (13 fibroadenomas and 10 diploid and 10 aneuploid carcinomas). No genomic
      imbalances were found in fibroadenomas. Recurrent findings in adenocarcinomas
      include copy number increases for chromosomes 1q (14 of 20 samples), 8q (10 of
      20), 17q (5 of 20), 6p (3 of 20), 13q (3 of 20), and 16p (3 of 20), and copy
      number decreases for chromosomes 22 (7 of 20), 17p (6 of 20), and 20 (3 of 20).
      Regional high level copy number increases were observed on chromosome bands 1q32,
      8p11, 8q24, 10p, 11q13, 12p, 12q15, 17q11-12, and 17q22-24. The majority of the
      samples were studied for gene amplification of c-myc, c-erbB2, cycD1, and int-2
      by means of Southern blot analysis. The comparison with DNA ploidy measurements
      revealed a different distribution and a significantly higher number of
      chromosomal aberrations in aneuploid tumors than in diploid tumors and in
      fibroadenomas.

PMID- 7585609
TI  - ERBB-2 (HER2/neu) gene copy number, p185HER-2 overexpression, and intratumor
      heterogeneity in human breast cancer.
AB  - Amplification of the ERBB-2 (HER-2/neu) gene is accompanied by overexpression of
      its cell surface receptor product, p185HER-2. Heterogeneity has been observed for
      both the gene copy number and the level of overexpression of its protein product.
      To better understand their relationship, correlation between the level of
      cellular expression of p185HER-2 and ERBB-2 gene amplification was studied in
      four human breast cancer cell lines (BT-474, SK-BR-3, MDA-453, and MCF-7) and in
      a primary human breast tumor sample. The relative expression of p185HER-2 was
      measured by immunofluorescence by using flow and/or image cytometry while
      correlated DNA analysis was performed on the same cells by fluorescence in situ
      hybridization to determine ERBB-2 gene and chromosome 17 copy numbers. Marked
      heterogeneity was observed in both protein expression and ERBB-2 copy number.
      Despite this heterogeneity, and in accordance with previous studies, the average
      levels of p185HER-2 expression correlated well with average ERBB-2 gene copy
      numbers in the four lines examined (r = 0.99). When the relationship between copy
      number and protein expression was studied on a cell-by-cell basis, p185HER-2
      expression correlated with both the absolute number of ERBB-2 gene copies/cell (r
      = 0.59-0.63) and chromosome 17 copy number (r = 0.45-0.61). It is of interest
      that there was weak or no correlation between p185HER-2 protein expression and
      the ERBB-2 copy number:chromosome 17 copy number ratio (r = 0.0-0.25). In more
      than one-half of cells expressing a high level of p185HER-2, the chromosome 17
      copy number was high (two or three times the average copy number), whereas < 2%
      of an unselected population had a high chromosome 17 copy number.
      Bromodeoxyuridine incorporation indicated that the S-phase-labeling index was
      homogeneous across various p185HER-2-expressing subpopulations in the SK-BR-3
      cell line. Analysis of the primary breast tumor sample showed results similar to
      the cell lines, supporting the strong possibility of a mechanistic link among
      p185HER-2 overexpression, ERBB-2 amplification, and high chromosome 17 copy
      number.

PMID- 7585613
TI  - Increase in suprabasilar integrin adhesion molecule expression in human epidermal
      neoplasms accompanies increased proliferation occurring with immortalization and
      tumor progression.
AB  - In a previous prospective study of 80 patients with squamous cell carcinoma of
      the upper aerodigestive tract, a progressive increase in expression of the
      integrin cell adhesion molecule alpha 6 beta 4 in suprabasilar cell layers of the
      tumor parenchyma was associated with an increase in early recurrence after
      therapy. In this study, we determined the relationship of the altered expression
      pattern of the integrin to changes occurring during benign, invasive, or
      metastatic stages of tumor development. Suprabasilar expression of integrin alpha
      6 beta 4 appeared with neoplastic transformation in benign squamous papillomas,
      but homogeneous expression occurred more frequently in the parenchyma of primary
      and metastatic squamous cell carcinomas. The variation in the extent of
      suprabasilar integrin expression among the tumors corresponded to the variation
      in the population undergoing proliferation as determined by two independent
      markers of proliferation. Integrin expression was quantified in primary, HPV 16
      DNA-immortalized, and v-ki-ras oncogene-transformed keratinocytes, and the
      pattern of expression was compared with cell cycle progression. Primary
      keratinocyte lines showed a bimodal distribution of integrin expression, with one
      population showing decreased integrin expression, cell size, and a block of cell
      cycle progression consistent with differentiation, whereas another population
      exhibited high integrin expression and full progression through the cell cycle,
      consistent with proliferation. HPV-immortalized and v-ki-ras-transformed cell
      lines undergoing continuous proliferation exhibited uniformly strong integrin
      expression, which was similar in intensity to that observed in the proliferating
      population of normal keratinocytes. Similar increases in expression of two
      additional integrins, alpha 2 beta 1 and alpha 3 beta 1, occurred along with
      integrin alpha 6 beta 4 in tissue specimens and cell lines derived from
      neoplasms. Thus, epidermal neoplasms display an increase in a population of cells
      exhibiting constitutive expression of a repertoire of integrins, which is similar
      to that found transiently in the acute phase of epidermal wound healing, a
      physiological response in which hyperproliferation, retention of multiple layers
      of proliferating cells, and migration occur. The association of a progressive
      increase in suprabasilar expression of these integrins with early tumor
      recurrence and advanced neoplasia suggests that constitutive expression and
      function of the same repertoire of integrins may be advantageous, rather than
      sufficient, for tumor progression.

PMID- 7585612
TI  - CD44 isoforms correlate with cellular differentiation but not with prognosis in
      human breast cancer.
AB  - CD44 is a transmembrane glycoprotein occurring in several isoforms with different
      extracellular regions. The various transcripts are encoded by one gene locus
      containing 20 exons, of which at least 10 can be alternatively spliced in nascent
      RNA. Isoforms encoded by the variant exons (termed CD44v) are highly restricted
      in their distribution in nonmalignant tissue as opposed to the standard form of
      CD44 (CD44s) abundant in many tissues. Specific variant isoforms containing exon
      6v have been shown to render nonmetastatic rat tumor cells metastatic. Based on
      the prominent role in rat metastasis formation, CD44v isoforms were suggested to
      be involved in human tumor progression. Correlations between prognosis and
      expression of CD44v have been reported for gastric and colon carcinoma, for non
      Hodgkin's lymphoma, and recently for breast carcinoma. We evaluated the
      expression of CD44 isoforms in node-positive (n = 119) and node-negative (n =
      108) cases of breast carcinoma by immunohistochemistry using CD44v exon-specific
      mAbs. In a subset of 43 cases of high-risk patients, reverse transcription-PCR
      was used to determine the exon composition of the transcripts. Protein and RNA
      expression data were probed statistically for their correlation to survival of
      the patients and clinical risk factors. In contrast to recently published data
      (M. Kaufmann et al., Lancet, 345: 615-619, 1995), in our cohort disease-free and
      overall survival data did not indicate significant correlations with the
      expression of the analyzed isoforms in univariate and multivariate analyses.
      Comparison of CD44 protein expression with established clinical risk factors for
      survival such as tumor size (pT1+pT2) and histological grading revealed
      correlations with the presence of CD44s (P = 0.02 and P = 0.03, respectively) and
      CD44-9v (P = 0.05 for histological grading). Carcinoma tissues with elevated
      estrogen and progesterone receptor levels showed positive correlation with CD44
      6v (P = 0.001), while a trend for significant coexpression of CD44s and CD44-9v
      isoforms was observed in estrogen receptor-positive tissues (P = 0.08 and 0.06,
      respectively). In breast cancer, CD44s, CD44-9v, and CD44-6v are apparently
      markers for cellular differentiation but not for tumor progression. Our data
      suggest that steroid hormone receptors may be associated with the in vivo
      expression of CD44-6v-containing isoforms in human mammary carcinoma.

PMID- 7585614
TI  - Cloning of a brain-type isoform of human Rab GDI and its expression in human
      neuroblastoma cell lines and tumor specimens.
AB  - Rab proteins, a family of Ras-related small GTP-binding proteins, play a key role
      in regulating intracellular vesicle trafficking. Rab GDP dissociation inhibitor
      (GDI3) forms a soluble complex with Rab proteins and thereby prevents the
      exchange of GDP for GTP. Recently, two isoforms of Rab GDI cDNA were isolated
      from rats and mice. In this study, we have isolated a brain-type isoform of human
      Rab GDI cDNA and examined its expression in neuroblastoma. We tentatively
      designate it as human Rab GDI alpha (hu GDI alpha) and another human Rab GDI, as
      human Rab GDI beta (hu GDI beta). Hu GDI alpha cDNA encodes a protein of 447
      amino acids with a deduced molecular weight of 50,200. Northern blot analysis
      revealed that hu GDI alpha gene is expressed abundantly in the brain but much
      less in other tissues, while hu GDI beta gene is ubiquitously expressed. All
      human neuroblastoma cell lines and tumor specimens examined express hu GDI alpha
      gene to various extents, while a human T cell leukemia cell line, MOLT3, does
      not. The levels of both hu GDI alpha and beta mRNA were constant in a human
      neuroblastoma cell line, NB1, during its neuronal differentiation, while Rab3A
      and neurofilament-L gene expression and the number of neurosecretory granules
      were elevated at this condition. These results suggest that hu GDI alpha gene
      expression is not related to the differentiation state of neuronal cells.

PMID- 7585615
TI  - Time-dependent behavior of interstitial fluid pressure in solid tumors:
      implications for drug delivery.
AB  - Elevated interstitial fluid pressure (IFP) may constitute a significant
      physiological barrier to drug delivery in solid tumors. Strategies for overcoming
      this barrier have not been developed to date. To identify and characterize
      various mechanisms regulating IFP and to develop strategies for overcoming the
      IFP barrier, we modeled the tumor as a poroelastic solid. We used this model to
      simulate the effect of changes in microvascular pressure and tumor blood flow
      (TBF) on IFP. To test model predictions, the effects of changes in arterial
      pressure and TBF on IFP were measured using a tissue-isolated tumor preparation.
      IFP in the center of an isolated tumor was predicted to follow variation of the
      arterial pressure with a time delay of the order of magnitude of 10 s, and this
      delay was found to be 11 +/- 6 s experimentally. Following a cessation of TBF,
      the time constant of the drop in IFP was predicted to be of the order of 1000 s
      and was found to be 1500 +/- 900 s experimentally. The former time scale is
      characteristic of transcapillary fluid exchange, and the latter of percolation of
      fluid through the interstitial matrix. Relying on the good agreement between
      theoretical predictions and experimental data, we estimated the effect of blood
      pressure modulation on macromolecular uptake in solid tumors. Our results show
      that no appreciable increase of macromolecular uptake should occur either by an
      acute or by a chronic increase of blood pressure. On the other hand, higher
      uptake would result from periodic modulation of blood pressure. Therefore, the
      effectiveness of a vasoconstrictor such as angiotensin II to increase
      macromolecular delivery should be significantly enhanced by periodic rather than
      bolus or continuous administration of the vasoactive agent.

PMID- 7585616
TI  - Apoptosis in tumors and normal tissues induced by whole body hyperthermia in
      rats.
AB  - Apoptosis in tumor and normal tissues was examined in rats treated with whole
      body hyperthermia (WBH; 41.5 degrees C for 2 h). WBH alone produced 0.5 day of
      tumor growth delay (TGD) in a fibrosarcoma and 5.8 days of TGD in the Ward colon
      carcinoma. This difference in WBH-induced TGD indicates that the fibrosarcoma is
      relatively resistant to WBH, whereas the Ward colon carcinoma is relatively heat
      sensitive. A quantitative histological assay for apoptosis demonstrated that the
      extent of apoptosis in the fibrosarcoma reached a maximum level of 19% 4 h after
      WBH and returned to the control level by 24 h. In contrast, WBH induced apoptosis
      with a peak value of 43% at 8 h in the Ward colon carcinoma, and the apoptotic
      level remained elevated above the control level until 48 h after WBH. Within
      normal tissues, the spleen and the lymph nodes showed WBH-induced apoptosis;
      however, the highest level of WBH-induced apoptosis as well as the most prolonged
      increase in apoptotic levels occurred in the thymus. The WBH-induced apoptosis in
      the thymus remained elevated above the control level until 48 h after WBH. Within
      the entire gastrointestinal tract, the small intestine was the most sensitive to
      WBH. Apoptotic cells were observed in the small bowel mucosa following WBH
      exposure. We also noted a minor WBH-induced increase in the apoptotic level in
      the bone marrow. Except for the case of the thymus, increased apoptotic levels in
      the normal tissues declined after peak levels at 4 h, and apoptosis above control
      levels was not seen beyond 12 h following WBH. Thus, within the normal tissues,
      WBH-induced apoptosis declined to basal levels within 12-48 h. These data
      indicate that both the extent and the kinetics of WBH-induced apoptosis differ
      between the two tumors and, meaningfully, between tumor and normal tissues. The
      extent and duration of apoptosis seem to correlate with tumor response to WBH.

PMID- 7585618
TI  - Molecular biology of cancer: implications for prevention and therapy--third Joint
      Meeting of the American Association for Cancer Research and the Japanese Cancer
      Association.

PMID- 7585617
TI  - Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and
      18q21 in an oral carcinoma and its derivative cell line.
AB  - A human papillomavirus (HPV) type 16 containing oral squamous cell carcinoma cell
      line 93VU147T at early passage was demonstrated to match its primary tumor with
      regard to HPV status and loss of heterozygosity at loci potentially involved in
      HPV-mediated carcinogenesis. DNA in situ hybridization of the cell line and the
      primary tumor revealed the presence of HPV 16 DNA clonally associated with the
      neoplastic cells. One- and two-dimensional Southern blot hybridization suggested
      HPV 16 to be integrated in the host genome at over hundred copies/cell. An
      identical restriction enzyme profile was observed for the tumor and the cell
      line. Viral DNA integration was confirmed by fluorescence in situ hybridization
      on metaphase spreads of the cell line, which revealed six stained loci comprising
      one at 15q14-15 and five at cytogenetically unidentifiable chromosomes. In
      addition, the tumor and the cell line displayed mRNA expression of the E6/E7
      region encoding the viral oncoproteins, as determined by reverse transcription
      PCR. Northern blot analysis of the cell line revealed three major and three minor
      transcripts harboring E6/E7 sequences. Both the primary tumor and cell line
      showed loss of heterozygosity at the 11q22 (D11S35) and 18q21 (DCC) loci. These
      data support a role for HPV 16 in the development of a subset of oral cancers,
      presumably in concert with loss of function of tumor suppressor genes at 11q and
      18q.

PMID- 7585619
TI  - Mismatch repair, somatic mutations, and the origins of cancer.
AB  - This paper outlines the basic properties of a newly recognized pathway that
      should enable somatic cells to generate double-stranded mutations in the complete
      absence of cell proliferation. Recognition of the existence of this pathway
      provides us with the basis for a better understanding of a number of important
      biological phenomena and, in particular, may help us to understand the origins of
      cancers in unselected human populations.

PMID- 7585621
TI  - Differential expression of CD44 splice variants in human pancreatic
      adenocarcinoma and in normal pancreas.
AB  - Immunohistochemical screening of pancreatic adenocarcinomas from 24 different
      patients and 9 pancreatic carcinoma cell lines revealed variant CD44 expression
      in all specimens tested. In contrast to normal pancreatic tissue, carcinomas were
      strongly positive for epitopes encoded by variant exons v5, whereas v6 was
      expressed on carcinoma cells as well as normal ductal pancreatic cells. Analysis
      of RNA expression revealed clear differences between normal pancreatic tissue and
      tumor specimens. In normal pancreas, v6 and v3 solely and one major chain
      consisting of v6-v10 were expressed, whereas in pancreatic carcinoma, multiple
      splice variants were detected. In about 80% of all carcinoma cases and all cell
      lines tested, the exon v5 appeared in the chain containing at least v4-v10. These
      data thus far suggest that not the presence alone but the chain composition of
      the CD44 variant chains could be important for their altered function because one
      of the major differences between normal and cancer tissue is the linkage of
      CD44v5 to the CD44v6-containing chain.

PMID- 7585620
TI  - Retroviral vector-mediated gene transfer of antisense cyclin G1 (CYCG1) inhibits
      proliferation of human osteogenic sarcoma cells.
AB  - Genetic changes found in human osteogenic sarcoma cells, including loss of the
      p53 and Rb tumor suppressor elements and overexpression of the cyclin G1 (CYCG1)
      proto-oncogene, suggest the potential of gene transfer as a treatment for
      metastatic disease. In this study, we examined the effects of antisense cyclin
      G1, in comparison with antisense cyclin D1 (CYCD1) and enforced expression of the
      universal cyclin-dependent kinase inhibitor p21WAF1/CIP1 on the proliferation of
      human MG-63 osteosarcoma cells. Retroviral vectors bearing antisense CYCG1 as
      well as antisense CYCD1 and WAF1/CIP1 (in sense orientation) driven by the
      Moloney murine leukemia virus long terminal repeat promoter inhibited the growth
      and/or survival of transduced MG-63 cells in 2-7 day cultures. This represents
      the first demonstration that cyclin G1 is essential for the survival and/or
      growth of human osteosarcoma cells. Cytostatic and cytopathic effects were
      accompanied by a significant increase in the incidence of apoptosis, as
      determined by immunocytochemical analysis of DNA fragmentation. Furthermore,
      transduction of MG-63 cells with a retroviral vector bearing the suicide gene,
      herpes simplex thymidine kinase (HStk), induced cell death on treatment with
      ganciclovir, exhibiting pronounced bystander effects. Taken together, the data
      affirm the feasibility of modulating inducible cell cycle control enzymes as a
      potential gene therapy approach in the clinical management of osteogenic sarcoma.

PMID- 7585622
TI  - Human homologue of a candidate for the Mom1 locus, the secretory type II
      phospholipase A2 (PLA2S-II), maps to 1p35-36.1/D1S199.
AB  - Mice heterozygous for the dominant Min mutation in their Apc gene develop
      multiple intestinal neoplasia. Analogously, family members from familial
      adenomatous polyposis kindreds inheriting mutations in their human APC homologue
      develop a similar phenotype. Quantitative trait loci studies have identified the
      Mom1 locus (for modifier of Min-1), which is responsible for part of the genetic
      variability in polyp number found among inbred mouse strains. The secretory type
      II phospholipase [nonpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been
      demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice
      carrying the Min mutation has been proposed to account for an increased polyp
      number compared to mice without the Pla2s-II mutation. In this study, we have
      mapped the chromosomal position of the human homologue of Pla2s-II. We have
      identified 3 mega-yeast artificial chromosomes that carry PLA2S-II and localized
      one of them by fluorescence in situ hybridization to the border between 1p35 and
      1p36.1. The presence of the microsatellite marker D1S199 in all three clones
      integrates PLA2S-II into different genetic maps. This highly polymorphic CA
      repeat D1S199 has previously been shown by us to identify loss of heterozygosity
      in 48% of sporadic colorectal tumors, indicating that the human homologue of the
      Pla2s-II/Mom1 locus might be related to human colorectal cancer.

PMID- 7585625
TI  - Human glutathione S-transferase M1 null genotype is associated with a high
      inducibility of cytochrome P450 1A1 gene transcription.
AB  - We investigated the transcriptional regulation of cytochrome P450 1A1 (CYP1A1)
      gene in human lymphoblastoid B cells and report that a high inducibility of
      CYP1A1 gene transcription by 2,3,7,8-tetrachlorodibenzo-p-dioxin is associated
      with glutathione S-transferase M1 (GSTM1) null genotype, whereas the presence of
      at least one GSTM1 allele is correlated with induction of only low levels of
      CYP1A1 mRNA by 2,3,7,8-tetrachlorodibenzo-p-dioxin. These data underline the
      major importance of the CYP1A1 inducibility phenotype associated with the
      homozygous GSTM1 null genotype in chemically induced cancers.

PMID- 7585624
TI  - Mitogen-activated protein kinase acts as a negative regulator of the heat shock
      response in NIH3T3 cells.
AB  - Exposure of NIH3T3 cells to elevated temperatures induces the phosphorylation and
      activation of mitogen-activated protein (MAP) kinases [or extracellular signal
      regulated kinases (ERKs)]. To investigate the significance of MAP kinase
      activation by heat shock, we examined the effect of inhibiting the activity of
      MAP kinase on heat shock protein 70 (hsp 70) expression. Overexpression of a
      dominant inhibitory mutant of ERK1, but not ERK2, in heat-shocked cells increased
      hsp70 reporter gene activity, suggesting that ERK1 acts as a repressor of hsp70
      gene expression. Increases in ERK1 activity through treatment of cells with
      sodium vanadate (SV), an inhibitor of the dual-specificity MAP kinase phosphatase
      1 (PAC1), resulted in increased phosphorylation of the heat shock transcription
      factor-1 (HSF-1) in unheated cells, delayed the activation of HSF-1 by heat
      shock, and inhibited the induction of hsp 70 by heat shock. Furthermore, the
      induction of thermotolerance was reduced significantly in cells that increased
      ERK1 activity by SV pretreatment. Immune complex kinase assays of heat shocked or
      SV-pretreated cells indicated that HSF-1 is a potential in vivo substrate for
      ERK1 phosphorylation. Taken together, these results suggest that agents that
      modulate MAP kinase act as negative regulators of the heat shock response in
      mammalian cells by modulating HSF-1 activity and hsp 70 expression.

PMID- 7585626
TI  - In vivo cisplatin-exposed macrophages increase immunostimulant-induced nitric
      oxide synthesis for tumor cell killing.
AB  - Mice pre-exposed to cisplatin increased their production of nitric oxide (NO)
      when treated with lipopolysaccharide (LPS). Peritoneal macrophages, isolated from
      mice 11 days after cisplatin treatment and cultured with LPS plus IFN-gamma,
      increased NO production, whereas the macrophages isolated 2 days after cisplatin
      treatment decreased it. In both cases, NO was not produced without
      immunostimulant(s). Northern and Western Blot analysis showed that macrophages
      exposed to cisplatin for 11 days increased production of mRNA and protein
      expression of inducible nitric oxide synthase (iNOS). THis result indicated that
      macrophages became more sensitive to LPS and IFN-gamma when they were exposed to
      cisplatin in vivo. Peritoneal macrophages, when activated with LPS plus IFN-gamma
      and then cocultured with several tumor cells, exhibited cytotoxic activity
      against both cisplatin-sensitive and cisplatin-resistant tumor cells. There was
      no difference in cytotoxicity between the paired cells. Under the same
      experimental condition, macrophages that were exposed to cisplatin for 11 days
      had significantly increased their cytotoxicity to the tumor cells. This cytotoxic
      activity was inhibited by the NOS inhibitor NG-monomethyl-L-arginine, indicating
      that NO is a major effector for macrophage-mediated tumor cell killing. Treatment
      of tumor cells with S-nitroso-N-acetylpenicillamine, a NO-generating compound,
      showed the similar tumoricidal effect. These data demonstrated that injection of
      cisplatin into the mice can enhance the sensitivity of macrophages to the
      subsequent treatment of immunostimulant(s) for effective tumor cell killing
      through enhanced NO production.

PMID- 7585627
TI  - Expression of Fas/APO-1 during the progression of astrocytomas.
AB  - Fas/APO-1 (CD95) is an apoptosis-signaling receptor molecule on the surface of
      cells. To investigate the possible role of Fas during malignant transformation of
      glial cells, we analyzed the expression of Fas mRNA by reverse transcription-PCR
      in human astrocytic brain tumors. Expression was found in 1 of 4 (25%) juvenile
      pilocytic astrocytomas (WHO grade I), 1 of 9 (11%) low-grade astrocytomas (WHO
      grade II), 6 of 12 (50%) anaplastic astrocytomas (WHO grade III), and all of 9
      glioblastomas (WHO grade IV). Thus, the frequency of Fas expression appears to
      correlate with the malignancy grade of astrocytomas. The soluble form of the Fas
      mRNA lacking the transmembrane domain was detected in one anaplastic astrocytoma
      and in two glioblastomas.

PMID- 7585628
TI  - Homozygous loss of the p15INK4B gene (and not the p16INK4 gene) during tumor
      progression in a sporadic melanoma patient.
AB  - Homozygous deletions of 9p21, including the cyclin-dependent kinase inhibitor
      genes p16INK4 and p15INK4B, have been reported frequently in melanoma (as well as
      other tumor) cell lines. Germline mutations within the p16INK4 gene have also
      been described in a proportion of familial melanoma kindreds, suggesting that
      p16INK4 is the 9p21 "melanoma" gene. We have previously concluded that deletion
      of this chromosomal region can occur early (before metastasis) and in vivo in
      sporadic melanoma due to the identification of identical hemizygous losses on
      9p21 in six autologous melanoma cell lines established from an individual patient
      (DX). These related cell lines have now been used to evaluate the timing of
      deletion/mutation of the p16INK4 and p15INK4B genes during tumor progression in
      melanoma. Surprisingly, homozygous deletions of a < or = 200-kb region
      surrounding p15INK4B, but not p16INK4, were detected in all six cell lines.
      Furthermore, single strand conformation polymorphism and sequencing analysis of
      the remaining p16INK4 allele in each case revealed only one intragenic mutation
      (in DX-6), whereas Western analysis provided evidence that p16INK4 protein was
      expressed in all six instances. These findings, taken together with those
      generated on other unrelated melanoma tumors and cell lines, suggest that
      hemizygous loss (or haplo-insufficiency) of the p16INK4 gene may be enough to
      place a melanocyte on a tumor pathway, and/or that the p16INK4 gene is not the
      sole 9p21 locus targeted in sporadic melanoma.

PMID- 7585623
TI  - Anti-retinoic acid (RA) antibody binding to human premalignant oral lesions,
      which occurs less frequently than binding to normal tissue, increases after 13
      cis-RA treatment in vivo and is related to RA receptor beta expression.
AB  - Nuclear retinoic acid receptor beta (RAR-beta) expression decreases in human
      premalignant oral lesions (POLs). RAR-beta suppression could result from a
      decrease in the cellular level of retinoids because RAR-beta gene transcription
      is enhanced by retinoids. To explore this hypothesis, we compared the binding of
      a monoclonal antibody (mAb) against all-transretinoic acid (RA; anti-RA mAbs) to
      normal oral tissue and POLs. All 7 normal specimens stained positive with the
      antibody compared to only 20 of 43 POLs; similarly, 7 of 7 normal specimens
      contained RAR-beta mRNA compared to only 14 of 43 POLs. Twenty-four specimens
      were available before and after a 3-month treatment with 13-cis-RA in vivo. Anti
      RA mAb binding to these specimens increased from 10 of 24 before to 22 of 24
      after treatment, and the expression of RAR-beta mRNA increased from 7 of 24
      before to 21 of 24 after treatment, respectively. There was a strong agreement
      between the binding of anti-RA mAbs and the expression of RAR-beta. Thus, we
      propose that the binding of anti-RA mAbs reflects the level of retinoids in the
      tissues and that this level is related strongly to RAR-beta expression.

PMID- 7585630
TI  - The oncogene qin codes for a transcriptional repressor.
AB  - The retroviral oncogene qin codes for a protein that belongs to the winged helix
      family of transcriptional regulators. The Qin protein is localized in the nucleus
      and binds to the same DNA consensus sequence as rat brain factor 1 (BF-1).
      Cellular Qin shows greater affinity to DNA than does viral Qin. Alone or fused to
      the DNA-binding domain of the yeast GAL4 protein, both Qin proteins act as
      transcriptional repressors. The major transcriptional repression domain maps to
      the region of amino acids 252-395 of viral Qin.

PMID- 7585629
TI  - Frequent expression of a mutant epidermal growth factor receptor in multiple
      human tumors.
AB  - The epidermal growth factor receptor has received much interest as a target for
      various antineoplastic agents, but a complication is that many normal tissues
      also express this receptor. We have previously identified in human glial tumors
      an 801-bp in-frame deletion within the epidermal growth factor receptor gene that
      created a novel epitope at the junction. By using Western blot assays with a
      mutant-specific antibody as a rapid and sensitive means for detecting this
      alteration in primary human tumors, it was found that 57% (26 of 46) of high
      grade and 86% (6 of 7) of low-grade glial tumors, but not normal brain, express
      this protein. This altered receptor was also present in 66% (4 of 6) of pediatric
      gliomas and 86% (6 of 7) of medulloblastomas, 78% (21 of 27) of breast
      carcinomas, and 73% (24 of 32) of ovarian carcinomas. The fact that this receptor
      is frequently found in tumors but not in normal tissue makes it an attractive
      candidate for various antitumor strategies.

PMID- 7585632
TI  - Microsatellite instability and mutations of the transforming growth factor beta
      type II receptor gene in colorectal cancer.
AB  - The TGF beta type II receptor (RII) was found to be mutated within a polyadenine
      tract in 100 of 111 (90%) colorectal cancers with microsatellite instability.
      Other polyadenine tracts of similar length were mutated in these samples but not
      as frequently as RII. In most cases, the polyadenine tract mutations affected
      both alleles of RII, and in four tumors heterozygous for the polyadenine
      mutations, three had additional mutations that were expected to inactivate the
      other RII allele. These genetic data support the idea that RII behaves like a
      tumor suppressor during CR cancer development and is a critical target of
      inactivation in mismatch repair-deficient tumors.

PMID- 7585631
TI  - A transforming growth factor beta receptor type II gene mutation common in colon
      and gastric but rare in endometrial cancers with microsatellite instability.
AB  - We have recently demonstrated that mutation of the transforming growth factor
      beta (TGF-beta) receptor type II (RII) gene is characteristic of colon cancers
      exhibiting microsatellite instability or replication errors (RER+). Moreover, we
      have shown that RII mutations in these RER+ colon cancers are characteristically
      frameshift mutations within a 10-bp polyadenine repeat present in the RII-coding
      region. We now show that RII gene mutations in this polyadenine repeat are also
      commonly present in RER+ gastric cancers (71%). In contrast, we find these same
      RII gene mutations are distinctly uncommon in RER+ endometrial cancers (17%, P <
      0.02). These results suggest that RII gene mutations confer a growth advantage
      and are selected for in RER+ cancers of both the upper and lower gastrointestinal
      tract. The genesis of RER+ endometrial tumors must, however, be by a different
      route.

PMID- 7585633
TI  - Adenovirus E1a-mediated tumor suppression by a c-erbB-2/neu-independent
      mechanism.
AB  - We reported previously that the adenovirus E1a gene reversed the transformed
      phenotype of one human melanoma and one fibrosarcoma cell line (S. Frisch, Proc.
      Natl. Acad. Sci. USA, 88: 9077-9081, 1991). To determine the generality of the
      tumor suppression effects of E1a, a diversity of tumor cell lines, including A204
      rhabdomyosarcoma, RD rhabdomyosarcoma, Saos-2 osteosarcoma, NCI-H23 non-small
      cell lung carcinoma, MDA-MB435S breast carcinoma, and ras-transformed MDCK kidney
      epithelial cells, were infected with a retrovirus bearing the 12S E1a coding
      sequence. We demonstrate here that the expression of E1a severely reduced the
      anchorage-independent and tumorigenic growth of these cell lines without
      affecting their growth under normal culture conditions. The parental tumor cells
      used in this study did not overexpress c-erbB-2/neu, and E1a did not affect its
      expression in these cells. Thus, tumor suppression by E1a can operate in a wide
      variety of human tumor cells by c-erbB-2/neu-independent mechanisms. E1a also
      sensitized these cell lines to the cytotoxic effects of the anticancer drugs
      etoposide and cisplatin. The results suggest that E1a could prove useful for the
      gene therapy of a wide variety of human cancers.

PMID- 7585634
TI  - Mutations in DNA mismatch repair genes are not responsible for microsatellite
      instability in most sporadic endometrial carcinomas.
AB  - Endometrial carcinoma is the second most common tumor type in women with
      hereditary nonpolyposis colorectal carcinoma. Microsatellite instability (MI) has
      been observed in the inherited (hereditary nonpolyposis colorectal carcinoma
      associated) form of endometrial carcinoma as well as in approximately 20% of
      presumably sporadic cases. Recent studies suggest that MI in many cell lines or
      xenografts derived from sporadic colorectal carcinomas is not attributable to
      mutations in four known human DNA mismatch repair (MMR) genes (hMSH2, hMLH1,
      hPMS1, and hPMS2). Mutational analyses of these four MMR genes in endometrial
      carcinomas have not been previously reported. We analyzed nine sporadic MI
      positive primary endometrial carcinomas for mutations in the above four MMR
      genes. Mutations were detected in two tumors (in hMSH2), and both of the
      mutations were acquired somatically. Immunohistochemical staining revealed a lack
      of expression of hMSH2 protein in the two tumors containing hMSH2 mutations. Our
      data suggest that mutations in these four known DNA MMR genes are not responsible
      for MI in the majority of sporadic endometrial carcinomas displaying this
      phenotype.

PMID- 7585635
TI  - Genetic radiotherapy overcomes tumor resistance to cytotoxic agents.
AB  - We report that radiation enhances gene therapy of a radioresistant tumor by
      upregulating the induction of a chimeric gene encoding a radiosensitizing
      protein, tumor necrosis factor alpha (TNF-alpha). We ligated the radiation
      inducible CArG elements of the radiation-inducible Egr-1 promoter/enhancer region
      upstream to the transcriptional start site of the human TNF cDNA (pE425-TNF).
      This construct was transfected using cationic liposomes into the variant murine
      fibrosarcoma cell line, P4L. The P4L cell line was both radioresistant (D0 = 188)
      and resistant to TNF. After a single intratumoral injection of 10 micrograms of
      pE425-TNF in cationic liposomes and two 20-Gy doses of irradiation, mean tumor
      volumes were significantly reduced in P4L tumors as compared to those receiving
      either pE425-TNF in liposomes or radiation alone (P = 0.01). TNf protein in P4L
      tumors was induced by radiation as high as 29 times control levels and remained
      detectable for 14 days. Our data indicate that combined gene therapy using
      liposomes, together with ionizing radiation to locally activate the induction of
      a radiosensitizing protein, is successful at overcoming resistance to both TNF
      and radiation.

PMID- 7585636
TI  - Activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human lung
      microsomes by cytochromes P450, lipoxygenase, and hydroperoxides.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific
      carcinogen, has been demonstrated to induce lung tumors in animals and is
      suspected to be a human carcinogen. Cytochromes P450 are the major enzymes
      responsible for the activation of NNK in microsomes from the lung and liver of
      rat and mouse, as well as human liver. The present study investigated the enzymes
      responsible for the metabolic activation of NNK in human lung microsomes. In the
      presence of a NADPH-generating system, the formation of keto aldehyde and keto
      alcohol (alpha-hydroxylation products, measured together), keto acid, hydroxy
      acid, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was observed in human
      lung microsomes. Carbon monoxide (90%) decreased the rate of NNK oxidation by 5
      49%, depending on the human lung microsomal samples analyzed. Coumarin decreased
      the oxidation of NNK by 9-34%, and an antibody against human P450 2A6 decreased
      the metabolism of NNK by 8-37%, suggesting the involvement of P450 2A6 in NNK
      oxidation. alpha-Napthoflavone inhibited NNK oxidation by 6-26%, possibly due to
      the inhibition of P450 1A1. P450 1A1-expressed microsomes catalyzed the formation
      of keto aldehyde and keto alcohol, exhibiting Km values of 1400 microM and 371
      microM, respectively. In the absence of NADPH, NNK metabolism resulted in the
      formation of keto acid, keto aldehyde, and keto alcohol, and the activities in
      different lung samples were decreased by indomethacin (100 microM; cyclooxygenase
      inhibitor) or nordihydroguaiaretic acid (100 microM; lipoxygenase inhibitor) by 0
      27% or 30-66%, respectively. The addition of arachidonic acid (10-100 microM)
      increased the rate of the formation of keto aldehyde and keto alcohol
      approximately 2-fold but inhibited the formation of keto acid. Soybean
      lipoxygenase increased the rate of formation of keto aldehyde and keto alcohol in
      a concentration-dependent manner. The increased rate in NNK oxidation by
      arachidonic acid or lipoxygenase was inhibited completely by nordihydroguaiaretic
      acid. Catalase, thiourea, and conjugated linoleic acid decreased the rate of NNK
      oxidation by 47, 20, and 45%, respectively. tert-Butyl-hydroperoxide, cumene
      hydroperoxide, and hydrogen peroxide increased the rate of formation of keto
      aldehyde and keto alcohol by 210, 40, and 50%, respectively. The results suggest
      that P450 enzymes are only partially responsible for the activation of NNK in
      human lung microsomes, and P450 2A6 or a P450 2A6-related enzyme seems to be
      involved in the activation. Furthermore, lipoxygenase and lipid hydroxperoxides
      may play important roles in the oxidation of NNK in human lung microsomes.

PMID- 7585639
TI  - Carcinogenicity studies of astemizole in mice and rats.
AB  - The histamine H1 antagonist astemizole (Hismanal) was tested for carcinogenicity
      in Swiss mice and Wistar rats. Astemizole was administered with the food to mice
      for 18 and to rats for 24 consecutive months. The doses given--approximately 5,
      20, and 80 mg/kg body weight.day--were equivalent to 25, 100, and 400 times,
      respectively, the recommended human dose of 10 mg/day. Survival of both mice and
      rats was comparable between groups. Peto's age-adjusted, dose-related trend
      analysis for the tumor-bearing rats did not reveal a statistically significant
      difference for males or females. There was no evidence that astemizole led to an
      increased incidence of spontaneously or unusually occurring neoplastic lesions in
      either mice or rats. Special attention was given to the effect of astemizole on
      the progression of spontaneously occurring mammary gland adenomas and
      fibroadenomas. Peto's analysis applied to the number of female rats bearing these
      benign mammary gland tumors disclosed no statistically significant dose-related
      trend. There was no positive trend for the onset of this tumor type, and the
      median size of the tumor over time per rat was also not statistically
      significantly different in a comparison of the control group with each of the
      dosed groups. The findings from these carcinogenicity studies suggest that
      astemizole is not tumorigenic and that it does not promote tumor growth.

PMID- 7585638
TI  - Effects of phenethyl isothiocyanate on the tissue distribution of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone and metabolites in F344 rats.
AB  - Phenethyl isothiocyanate (PEITC), a naturally occurring chemopreventive agent,
      inhibits lung tumor induction in rats by the tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, we examined
      the mechanism of tumor inhibition by determining the effects of dietary PEITC on
      levels of NNK and its metabolites in various tissues of NNK-treated F344 rats.
      F344 rats were fed control or PEITC-containing diets (3 mumol/g diet) before and
      throughout NNK treatment. To study NNK metabolism and distribution under both
      short-term and chronic NNK/NNK+PEITC treatments, control and PEITC-treated groups
      were divided into four subgroups. Subgroups were treated with either a single
      injection of [5-3H]NNK (1.76 mg/kg) or a total of 12, 24, and 36 doses of NNK
      administered three times/week. After a final injection of [5-3H]NNK in each
      subgroup, the rats were sacrificed at various time intervals, and NNK and its
      metabolites in lung, liver, nasal mucosa, pancreas, kidney, stomach, and serum
      were measured. Time-course curves for the tissue metabolites were generated, and
      the areas-under-the-curves were compared. We observed that lung, liver, and nasal
      mucosa, target tissues of NNK carcinogenesis in F344 rats, were also the tissues
      that had the highest levels of alpha-hydroxylation metabolites relative to NNK
      and its carbonyl reduction metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL). The most pronounced effect of PEITC was a reduction in levels of
      alpha-hydroxylation metabolites in most tissues examined (except nasal mucosa).
      The ratio of alpha-hydroxylation products to NNK + NNAL in most tissues was
      decreased by PEITC, indicating that alpha-hydroxylation of NNK/NNAL was
      inhibited. PEITC did not significantly affect the total levels of NNK and its
      metabolites in the lung and most tissues examined, indicating that PEITC does not
      alter the amount of NNK reaching the lung. These results support the hypothesis
      that inhibition of NNK-induced lung tumorigenesis by PEITC is a result of
      decreased metabolic activation of NNK.

PMID- 7585640
TI  - Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma.
AB  - This study was undertaken to determine the extent of apoptosis in lung carcinoma
      and to evaluate it as a prognostic marker. A series of 75 lung carcinomas (47
      squamous cell carcinomas, 24 adenocarcinomas, 3 small cell carcinomas, and 1
      large cell carcinoma) was analyzed for the extent of apoptosis by using the 3'
      end-labeling method of DNA in tissue sections. Apoptosis was correlated with the
      rate of cell proliferation, the immunohistochemically detectable p53 and bcl-2,
      the extent of tumor necrosis, and the survival data. The end-labeling method
      allowed a precise evaluation of the extent of apoptosis. In tumor tissue, the
      number of apoptotic bodies was roughly 2-fold greater than the number of
      apoptotic cells, whereas in nonneoplastic control tissues, the ratio was 1:1. The
      apoptotic indexes (percentages of apoptotic cells and bodies among tumor cells)
      were slightly higher in adenocarcinoma than in squamous cell carcinoma. There was
      no association between the extent of apoptosis and the expression of
      proliferating cell nuclear antigen or p53. On the other hand, tumor necrosis
      correlated significantly with proliferating cell nuclear antigen and p53
      positivity (P = 0.00025 and 0.00087, respectively). Surprisingly, the extent of
      apoptosis was also found to be independent of the expression of bcl-2. Patients
      with apoptotic indexes greater than 1.5% had significantly shorter survival time
      than patients with apoptotic indexes equal to 1.50% or less (P < 0.01 by log
      rank). Aberrant p53 positivity also predicted a poor prognosis (P < 0.002 by log
      rank). By multivariate analysis, enhanced apoptosis showed a 1.9-fold risk (P =
      0.04), and p53 positivity showed a 2.3-fold risk (P = 0.005) for a shortened
      survival. We conclude that both enhanced apoptosis and p53 positivity are
      independent prognostic markers in non-small cell lung carcinoma, predicting
      shortened survival time of the patients.

PMID- 7585637
TI  - Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1
      metabolism in human hepatocytes in primary culture.
AB  - Dithiolethiones are thought to act as potent chemoprotective agents against
      aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rat by inducing
      glutathione S-transferases (GSTs). To determine whether these antioxidants can be
      similarly effective in human beings, we have investigated metabolism of AFB1, in
      primary human hepatocytes with or without pretreatment by oltipraz (OPZ), a
      synthetic derivative of the natural 1,2-dithiole-3-thione. Aflatoxin M1 (AFM1),
      glutathione conjugates of AFB1 oxides (AFBSGs), and unchanged AFB1 were
      quantitated in cultures derived from eight human liver donors. Parenchymal cells
      obtained from the three GST M1-positive livers metabolized AFB1 to AFM1 and to
      AFBSGs derived from the isomeric exo-and endo-8,9-oxides, whereas no AFBSGs were
      formed in the GST M1-null cells. Pretreatment of the cells with 3
      methylcholanthrene or rifampicin, inducers of CYP1A2 and CYP3A4, respectively,
      caused a significant increase in AFB1 metabolism. Although OPZ induced GST A2,
      and to a lesser extent GST A1 and GST M1, it decreased formation of AFM1 and
      AFBSG, which involves CYP1A2 and CYP3A4. Inhibition by OPZ of AFB1 metabolism by
      reducing CYP1A2 and CYP3A4 was also demonstrated by decreased activity of their
      monooxygenase activities toward ethoxyresorufin and nifedipine, respectively. The
      significant inhibition by OPZ of human recombinant yeast CYP1A2 and CYP3A4 was
      also shown. These results demonstrate that AFBSG can be formed by GST M1-positive
      human hepatocytes only, and suggest that chemoprotection with OPZ is due to an
      inhibition of activation of AFB1, in addition to a GST-dependent inactivation of
      the carcinogenic exo-epoxide.

PMID- 7585641
TI  - Retinoid refractoriness occurs during lung carcinogenesis despite functional
      retinoid receptors.
AB  - Retinoids have demonstrated activity in the prevention of second primary tumors
      in patients with non-small cell lung cancer (NSCLC). They also contribute to the
      normal growth and differentiation of human bronchial epithelial (HBE) cells.
      Because retinoids mediate their actions through retinoid nuclear receptors (RARs
      and RXRs), aberrant signaling through retinoid receptors could contribute to lung
      carcinogenesis. Using a lung carcinogenesis model consisting of normal,
      premalignant, and malignant HBE cells, we examined all-trans retinoic acid (t-RA)
      induced changes in cellular growth. These studies revealed that t-RA treatment
      inhibited the growth of normal HBE cells, but premalignant and malignant HBE
      cells were relatively resistant to t-RA. Coincident with the development of
      retinoid refractoriness, basal expression of the retinoic acid nuclear receptor
      beta (RAR-beta) increased. Analysis of receptor function by gel shift and
      transient transfection assays of normal, premalignant, and malignant HBE cells
      demonstrated that receptor-DNA binding and transcriptional activation properties
      were intact in the t-RA-refractory malignant HBE cells. To compare these findings
      to NSCLCs in patients, we investigated retinoid receptor expression in NSCLC
      biopsies. A subset of the tumors expressed RAR-beta, reflecting the RAR-beta
      expression observed in the malignant HBE cells in culture. These findings
      demonstrate that retinoid receptor function was intact in the t-RA-refractory
      malignant HBE cell line, suggesting that the defect in retinoid signaling in this
      lung carcinogenesis model is not intrinsic to the retinoid receptors.

PMID- 7585642
TI  - High levels of DNA adducts in human colon are associated with colorectal cancer.
AB  - Colon cancer is one of the most frequent causes of cancer death in western
      countries. Epidemiological studies suggest that colorectal cancer can be
      attributed, at least in part, to carcinogens and mutagens present in the diet
      and/or the environment. The covalent binding of these xenobiotics or their
      reactive metabolites to DNA is believed to initiate this chemical carcinogenesis.
      In the present study, using a 32P-postlabeling method, we investigated DNA adduct
      levels in control colons from patients without colorectal adenocarcinoma and in
      nontumoral and tumoral tissues from patients with colorectal adenocarcinoma. Our
      results show that the DNA adduct level is significantly higher (P < 0.001) in
      nontumoral than in control or tumoral colon samples. For the first time, we
      demonstrate in humans that the presence of numerous adducts in colonic mucosa is
      associated with colorectal cancer, a finding in agreement with the importance of
      chemical factors in causing this disease; therefore, after confirmation of the
      link between DNA adducts and colorectal cancer, the measurement of DNA adduct
      levels in colon samples could constitute a useful approach to the early detection
      of colorectal cancer.

PMID- 7585643
TI  - Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid
      carcinomas from children exposed to the Chernobyl nuclear accident.
AB  - Since the Chernobyl nuclear reactor accident, a striking increase of thyroid
      carcinoma has been reported in children exposed to radiation in Belarus. Because
      of its unprecedented scale and its emotional implications, this finding has
      raised concern and called the attention of the scientific community to this major
      health problem. Although epidemiologically documented, a direct correlation
      between thyroid cancer and radiation exposure has not been definitely proven at
      the molecular level. On the assumption that ionizing radiation could cause
      specific and common cancer-associated genetic lesions, an analysis of oncogene
      activation and/or tumor suppressor gene inactivation would help to define
      radiation-induced thyroid carcinomas. Therefore, we have analyzed by different
      molecular approaches, including Southern blotting, DNA transfection assay on NIH
      3T3 cells, and reverse transcription-PCR analysis, six papillary carcinomas from
      children living in the region of Belarus at the time of the Chernobyl nuclear
      accident to identify tumor-specific gene rearrangements of the proto-oncogenes
      RET and TRK, previously found activated in a tumor type-specific manner in
      papillary thyroid carcinoma. Using Southern blot analysis in four cases, we could
      detect specific rearranged bands indicating an oncogenic activation of RET that
      in three cases resulted in rearranged sequences provided by the same activating
      gene. Moreover, the DNA of the last three cases showed a biological activity in
      transforming NIH-3T3 cells after the DNA-mediated transfection assay, and the
      respective NIH-3T3 transfectants were found to express the oncogenic fusion
      transcripts. These results support the possibility that RET oncogenic activation
      could represent a major genetic lesion associated with thyroid carcinoma in
      children exposed to the Chernobyl nuclear accident.

PMID- 7585645
TI  - The distribution of the deleted in colon cancer (DCC) protein in human tissues.
AB  - A gene called deleted in colon cancer (DCC) has been identified on a region of
      chromosome 18, which is deleted in 70% of colorectal cancers. The DCC gene
      encodes a protein belonging to the immunoglobulin superfamily with similarity to
      the N-CAM transmembrane proteins and is a putative tumor-suppressor gene.
      Alternative splicing of transcripts of transmembrane proteins, including N-CAM,
      is known to occur, resulting in different isoforms of the protein. Using five
      antibodies against the DCC gene product (three monoclonal antibodies raised in
      our laboratory, one commercially available antibody, and a rabbit polyclonal
      antibody), we have demonstrated by immunostaining a DCC protein isoform in
      reticuloendothelial cells in human thymus, tonsil, and lymph node. This can be
      distinguished from another isoform described in normal colonic epithelium,
      because this latter is not demonstrable with the antibodies we have used. It
      could not be detected in normal colonic epithelium, polyps or colorectal
      carcinomas. This restrictive distribution suggests that not all DCC gene products
      are important in colonic cancer.

PMID- 7585644
TI  - Chemopreventive activity of tamoxifen, N-(4-hydroxyphenyl)retinamide, and the
      vitamin D analogue Ro24-5531 for androgen-promoted carcinomas of the rat seminal
      vesicle and prostate.
AB  - We evaluated the ability of dietary N-(4-hydroxyphenyl)retinamide; 1 alpha,25
      dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531); and
      tamoxifen to inhibit the development of androgen-promoted carcinomas of the
      accessory sex organs of male Lobund-Wistar rats. Invasive carcinomas of the
      seminal vesicle (SV) and anterior prostate (AP) were induced in Lobund-Wistar
      rats with three different combinations of initiator [N-nitroso-N-methylurea
      (NMU)] and promoter [testosterone propionate (TP)]: (a) high-dose NMU (30 mg/kg)
      + high-dose TP (20 mg via implant every 2 months); (b) high-dose NMU + low-dose
      TP (10 mg implanted every 2 months); or (c) low-dose NMU (15 mg/kg) + low-dose
      TP. During the period of TP administration, rats were fed a diet supplemented
      with either N-(4-hydroxyphenyl)retinamide (1 or 2 mmol/kg diet), Ro24-5531 (1.25
      or 2.5 nmol/kg diet), tamoxifen (0.5 or 5 mg/kg diet), or vehicle alone. After
      sacrifice at 8.5 or 11 months, the prostate-seminal vesicle complex from each rat
      was processed in toto and histologically staged as to the extent of tumor
      involvement. In animals given low-dose TP, all three agents were significantly
      effective at reducing the incidence of invasive carcinomas of the SV and, to a
      lesser degree, the AP. Of the three agents, tamoxifen given in high dose (5
      mg/kg) had the strongest activity, reducing the occurrence of invasive SV
      carcinomas from 72-83% in controls to 6% (P = 0.0001) and the occurrence of
      invasive AP carcinomas from 50-72% to 18-22% (P < 0.05).

PMID- 7585646
TI  - Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast
      cancer cell line and decreases cell growth.
AB  - In a previous study, we found that morphine decreases, in a dose-dependent
      manner, the cell growth of T47D human breast cancer cells, despite the lack of mu
      opioid receptors and an interaction of morphine with other opioid sites. We have
      therefore examined a possible interaction of morphine with other membrane
      receptor systems of the cell. The present study describes for the first time an
      interaction between mu-acting opioid drugs and the somatostatinergic system. We
      have found that [125I]Tyr11-somatostatin binds with high affinity to T47D cells.
      Analysis of the binding data showed the presence of two components: one with high
      affinity but low capacity (Kd, 0.145 nM; 1450 sites/cell), and another of lower
      affinity but higher capacity (Kd, 1.192 nM; 11920 sites/cell). Somatostatin-14
      and somatostatin-28 showed multiphasic displacement curves, indicating
      heterogeneity of binding sites. The latter was confirmed by reverse transcription
      PCR, which revealed the existence of the somatostatin receptor subtypes 2 and 3
      (SSTR2 and SSTR3), with a relative mRNA concentration of 85 and 15%,
      respectively. Morphine and the morphinomimetic peptide morphiceptine (Tyr-Pro-Phe
      Pro-NH2) displace somatostatin from its binding sites. Further analysis indicated
      that mu-acting opioids interact with the SSTR2 receptor subtype.

PMID- 7585647
TI  - Growth inhibition of human cancer metastases by camptothecins in newly developed
      xenograft models.
AB  - Several metastatic models have been developed using clonal selection of human
      malignant cells metastasizing into a specific organ in NIH-I Swiss
      immunodeficient mice. The organs of choice were the central nervous system (CNS),
      targeted by metastases of malignant melanoma, and the liver, with metastases of
      colon adenocarcinoma. Additional models of adrenal metastases by malignant
      melanoma, and CNS involvement by implanted human lung squamous carcinoma or
      lymphoblastoid cells, are also available. Organ metastases, as well as the
      effects of treatment, were confirmed by autopsies and histological examination of
      the tissues or by a surgical inspection of the liver. The treatment end points
      were established as the increases in survival times of treated mice relative to
      placebo-treated controls. Camptothecins injected i.m. or delivered via
      gastrointestinal tract inhibit the growth of CNS metastases and increase the
      survival of treated animals. 9-Amino-20(S)-camptothecin was effective in the CNS
      model and in the model of liver metastases. The drug increased 3.3- and 5.7-fold
      the survival rates relative to untreated controls with metastases of colon
      adenocarcinoma to the liver, and all camptothecins were significantly more
      effective than 5-fluorouracil, currently a drug of choice in treatment of this
      disease. The xenograft models of metastases are available for studies of drug
      passage through the blood-brain barrier optimization of drug delivery to the
      liver, and for the development of new camptothecin-based treatment strategies.

PMID- 7585648
TI  - B-lymphoma cells are activated by peptide ligands of the antigen binding receptor
      or by anti-idiotypic antibody to induce extracellular acidification.
AB  - Synthetic peptide ligands specific for the surface immunoglobulin receptor of the
      human Burkitt's lymphoma cell line SUP-B8, previously identified using phage
      display libraries, induced apoptosis of the SUP-B8 cells in vitro when
      administered as dimers or tetramers. The use of synthetic peptide ligands is
      being explored for immunotherapy of B-cell lymphoma. It will be critical to
      identify which of the peptide ligands identified are the most active
      functionally. Using the Cytosensor microphysiometer, SUP-B8 cells and B-lymphoma
      cells obtained from patients were found to acidify their extracellular
      environment within minutes of specific activation by surrogate peptide ligands or
      by anti-idiotype antibodies. This signal was blocked by pretreatment of the
      lymphoma cells with the tyrosine kinase inhibitor genistein. Treatment of SUP-B8
      cells with dimeric and tetrameric specific peptide ligands caused a rapid
      increase in extracellular acidification rate, which peaked after 10 min at
      approximately 15 and 20% above basal rates, respectively. These responses were
      blocked by excess monomeric peptide. To evaluate the ability of different peptide
      ligands to induce a signal directly on lymphoma cells, thereby establishing their
      relative affinity to the surface immunoglobulin receptor, acidification rate
      changes were measured at varying peptide concentrations. The microphysiometer
      signal correlated with the known relative affinities and antiproliferative
      potencies of the peptides. This approach is particularly useful for primary tumor
      cells that cannot be cultured. The signal may be predictive of the efficacy of
      treatment with synthetic peptide ligands and may be useful in the evaluation of
      ligands for other cell surface receptors with biological effects on B-lymphoma
      cells.

PMID- 7585651
TI  - Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine
      sarcoma cell lines defective in mismatch repair activity.
AB  - We have examined a panel of gynecological sarcomas for microsatellite
      instability. The genomic DNA from 11 of 44 sarcomas contained somatic alterations
      in the lengths of one or more di-, tri-, tetra-, or pentanucleotide
      microsatellite sequence markers, and 6 of these cases had alterations in two or
      more markers. In addition, di-, tri-, and tetranucleotide microsatellites were
      found to be highly unstable in single cell clones of two cell lines derived from
      a uterine mixed mesodermal tumor. Since such instability is characteristic of
      cells defective in postreplication mismatch repair, we examined mismatch repair
      activity in extracts made from these lines. Both extracts were repair deficient,
      while an extract of another gynecological sarcoma cell line not exhibiting
      microsatellite instability was repair proficient. The repair deficiency was
      complemented by a colon tumor cell extract that was defective in the hMLH1
      protein but not by an extract defective in hMSH2 protein. This suggested that the
      defect in the uterine sarcoma line could be in hMSH2. Subsequent analysis of the
      gene revealed a 2-bp deletion in exon 14, leading to premature truncation of the
      hMSH2 protein at codon 796 and no detectable wild-type gene present. These data
      suggest that the microsatellite instability observed in these cell lines, and
      possibly in a significant number of gynecological sarcomas, is due to defective
      postreplication mismatch repair. There was no apparent correlation with
      microsatellite instability and clinical outcome.

PMID- 7585649
TI  - Methylcholanthrene-induced mouse sarcomas express individually distinct major
      histocompatibility complex class I-associated peptides recognized by specific
      CD8+ T-cell lines.
AB  - Mouse sarcomas induced by methylcholanthrene (MC) are immunologically distinct
      even if they are induced in the same strain of mice. T-cell lines were derived
      from mice immunized against a series of syngeneic MC sarcomas on B6 background,
      known to carry unique tumor-specific transplantation antigens. Tumor necrosis
      factor-alpha (TNF-alpha) release assays concurred with the in vivo rejection
      tests. The strongest response in the TNF-alpha release was always obtained with
      the corresponding tumor, with very limited cross-reactivity against five other MC
      tumors or two virally induced B6 lymphomas. The specific TNF-alpha release from
      the anti-MC tumor CTL lines was mainly mediated by CD8+ cells. T-cell lines from
      intact and CD4-/- mice gave a similarly specific pattern. In contrast, T-cell
      lines derived from CD8-/- mice cross-reacted with several other MC-induced
      tumors. Peptides eluted from MC sarcomas under mild acid conditions were
      fractionated by reverse-phase high performance liquid chromatography and tested
      for their ability to sensitize the processing- and presentation-defective mutant
      RMA-S line. Only one high performance liquid chromatographic fraction from each
      of the three different tumor-derived peptide eluates capacitated RMA-S to induce
      TNF-alpha release and sensitized the cell to the cytotoxic effect of the
      corresponding tumor-specific T-cell line. A different Kb-restricted peptide
      fraction was active for each of the three MC sarcomas tested, indicating that
      they all expressed individually distinct peptide epitopes.

PMID- 7585652
TI  - Association of minisatellite instability with c-myc amplification and K-ras
      mutation in methylcholanthrene-induced mouse sarcomas.
AB  - Instability of microsatellite sequences are frequently found in human tumors. In
      addition, minisatellite sequences, another group of highly unstable sequences,
      serve as sensitive markers of genetic instability. We have studied minisatellite
      instability in methylcholanthrene-induced mouse sarcomas. These sarcomas
      frequently carry the amplified c-myc gene. Seven sarcomas without the
      amplification and seven others with the amplification were selected randomly.
      Regardless of the state of the c-myc gene amplification, these sarcomas exhibited
      a varying degree of transplantability in syngeneic mice. The hypervariable mouse
      minisatellite locus Ms6hm was found to be highly unstable, specifically among
      sarcomas with the amplified c-myc gene. However, chromosome instability, as
      analyzed by micronucleus assay, was observed similarly for two groups of
      sarcomas. In addition, transversion of G to C and A to T was detected at the K
      ras gene in four of the seven sarcomas with the amplified c-myc gene, and these
      mutations are thought to be induced directly by methylcholanthrene. Thus,
      concomitant occurrence was observed for three seemingly unrelated mutations,
      amplification of the c-myc locus, point mutation of the K-ras gene, and
      instability at the hypervariable mouse minisatellite locus. The present study
      indicates a possible involvement of K-ras mutation and c-myc amplification in
      induction of genetic instability in methylcholanthrene-induced mouse sarcomas.

PMID- 7585650
TI  - Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone
      disorder xeroderma pigmentosum group D.
AB  - Xeroderma pigmentosum (XP) is a sun-sensitive, cancer-prone genetic disorder
      characterized by a defect in nucleotide excision repair. The human nucleotide
      excision repair and transcription gene ERCC2 is able to restore survival to
      normal levels after exposure to UV light in XP complementation group D cells. No
      enhancement of UV survival is seen in groups C, E, F, or G. XP-CS-2 cells are
      complemented by ERCC2, confirming the reassignment to group D of this combined
      XP/Cockayne's syndrome patient. Nucleotide sequence analysis of the ERCC2 cDNA
      from five XP group D cell strains [XP6BE(SV40), XP17PV, XP102LO, A31-27 (a
      HeLa/XP102LO hybrid), and XP-CS-2] revealed mutations predominantly affecting
      previously identified functional domains. The mutations include base
      substitutions resulting in amino acid substitutions, deletions due to splicing
      alterations, and defects in expression. XP6BE(SV40), XP17PV, XP102LO, and A31-27
      all have one allele with an Arg683 to Trp substitution within the putative
      nuclear location signal. The genetic disorder trichothiodystrophy (which is not
      cancer-prone) can also result from mutations in the ERCC2 gene, some of which are
      the same as those found in XP-D. The various clinical presentations can be
      correlated with the particular mutations found in the ERCC2 locus.

PMID- 7585653
TI  - Alterations of microsatellites in neurofibromas of von Recklinghausen's disease.
AB  - von Recklinghausen's disease, or type I neurofibromatosis, a common familial
      tumor syndrome, is characterized by the occurrence of multiple benign neoplasms
      of nerve sheath cells. The disease is caused by germ-line mutations of the NF1
      gene, which encodes a member of the GTPase-activating superfamily of Ras
      regulatory proteins. We analyzed 5 dinucleotide repeat loci in DNAs from
      neurofibromas and matched normal skin from 16 NF1 patients. Eight cases (50%)
      manifested microsatellite alterations. Expansions or compressions of dinucleotide
      repeats were observed at one locus in four cases and at two loci in one case.
      Banding patterns compatible with the loss of a microsatellite allele were
      observed in four cases, including one that also presented microsatellite
      instability. The surprisingly high frequency of microsatellite alterations
      suggests that the NF1 gene or another gene(s) contributing to the pathogenesis of
      neurofibromas might be directly or indirectly implicated in the control of
      genomic integrity.

PMID- 7585654
TI  - Deletion of chromosome 1p loci and microsatellite instability in neuroblastomas
      analyzed with short-tandem repeat polymorphisms.
AB  - We have analyzed DNA from 46 neuroblastoma tumors of all clinical stages and five
      ganglioneuroma tumors together with corresponding control DNA for loss of
      heterozygosity (LOH) on the distal 1p chromosomal region (1p-LOH). The markers
      used for the analyses were genetically mapped DNA polymorphisms detectable with
      PCR analysis. In general, there was concordance among aggressive tumor stage, 1p
      deletion, and N-myc amplification, although exceptions were found. Twelve (26%)
      of the 46 neuroblastoma tumors displayed 1p-LOH, 11 being stage 4 and 1 stage 2
      (which progressed subsequently to stage 4), whereas 10 stage 4 tumors showed no
      1p-LOH. Of 12 neuroblastomas shown to have N-myc amplification, 10 had 1p-LOH. In
      8 cases it was possible to test for parental origin of the chromosome involved in
      1p-LOH. No significant correlation between LOH and paternal or maternal allele
      was found. Commonly deleted loci in the distal 1p region in the neuroblastoma
      tumors indicated that the region for a tentative neuroblastoma tumor suppressor
      gene is defined proximally by marker D1S244 and distally by marker D1S80. One
      striking feature of three stage 2 neuroblastomas and one of the stage 3 tumors
      was the presence in the tumor DNA of alleles not present in the constitutional
      DNA of the patients, i.e., microsatellite instability. The significance of this
      phenomenon in localized neuroblastoma tumors remains to be clarified. Aggressive
      neuroblastoma in young children (younger than 2 years of age) seems to be a
      homogenous disorder consistently showing concomitant 1p-LOH and N-myc
      amplification. In the majority of unfavorable neuroblastoma in older children,
      however, neither 1p-LOH nor N-myc amplification could be detected. This indicates
      that neuroblastoma in older children is a biologically more heterogenous disorder
      in which genetic alterations other than deletions of chromosome 1p and
      amplification of N-myc also may contribute to tumorigenesis.

PMID- 7585655
TI  - Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR,
      in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death
      caused by ionizing radiation.
AB  - Vascular endothelial growth factor (VEGF) has been identified as a peptide growth
      factor specific for vascular endothelial cells. In this study, we demonstrated
      the expression of the KDR gene transcript, which encodes a cell surface receptor
      for VEGF, in normal human hematopoietic stem cells, megakaryocytes, and platelets
      as well as in human leukemia cell lines, HEL and CMK86. Moreover, we showed the
      expression of VEGF gene transcript in these normal fresh cells and cell lines. To
      elucidate biological functions of VEGF on hematopoiesis, we determined whether
      this growth factor has mitogenic activity to hematopoietic cells or the ability
      to suppress apoptotic cell death. The liquid culture and colony-formation assay
      revealed that VEGF suppressed apoptotic cell death of both CMK86 cells and normal
      hematopoietic stem cells caused by gamma-ray irradiation, although mitogenic
      activity of VEGF was not detected. The ability of VEGF to suppress apoptotic cell
      death was independent of the change of cell cycle distribution. These data
      suggest that VEGF may play an important role in survival or maintenance of
      hematopoietic stem cells due to the prevention of apoptotic cell death caused by
      some stresses such as ionizing radiation and that VEGF may give leukemia cells
      some abilities of resistance against radiotherapy in an autocrine or paracrine
      manner.

PMID- 7585658
TI  - Photodynamic therapy.

PMID- 7585659
TI  - Bone marrow transplantation from volunteer unrelated donors.

PMID- 7585656
TI  - Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers:
      correlation with overall survival.
AB  - Few molecular genetic alterations have been identified in endometrial cancers
      that are associated with poor clinical outcome. Overexpression of HER-2/neu,
      transforming growth factor alpha, and p53 proteins have all been associated with
      poor prognosis in women with endometrial cancer. In this study, the level of HER
      2/neu gene amplification and expression was characterized in 92 endometrial
      cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER
      2/neu gene copy number, and immunohistochemistry was used to characterize
      expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as
      showing moderate or high immunostaining. HER-2/neu gene amplification was
      detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results
      were both available for 80 cases. Fourteen of these cases showed both moderate or
      high immunostaining and gene amplification. Clinical follow-up information was
      available for 76 women in this study. Women whose endometrial cancer exhibited
      HER-2/neu gene amplification by FISH had a shorter overall survival than women
      whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with
      moderate or high HER-2/neu immunostaining were associated with a lower cumulative
      overall survival than tumors with low immunostaining by log rank analysis (P <
      0.0001). Multivariate analysis of survival rates revealed HER-2/neu
      overexpression to be an independent predictor of overall survival (P = 0.0163).
      Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or
      radiation therapy was associated with an improved overall survival (P = 0.039).
      However, among those women whose tumor lacked overexpression, overall survival
      was not improved by adjuvant treatment.

PMID- 7585662
TI  - Brain stem dermoid cyst.

PMID- 7585661
TI  - Transforming growth factor beta and cancer.

PMID- 7585657
TI  - Angiofollicular lymph node hyperplasia (Castleman's disease).
AB  - This review provides a comprehensive assessment of angiofollicular lymph node
      hyperplasia (ALNH) or Castleman's disease including pathogenesis, clinical
      presentation, histomorphologic and immunophenotypic findings, laboratory results,
      treatment, and prognosis. A division of ALNH into clinically relevant subtypes
      provides a framework for the consideration of the disorder. A comprehensive
      search of the medical literature involving ALNH using Medline was performed.
      Reports judged to be significant for the understanding of the disorder were
      analyzed and their findings incorporated into this review. ALNH is divided into
      localized/unicentric ALNH and generalized/multicentric ALNH due to the profound
      clinical differences seen between these variants. Localized/unicentric ALNH is
      separated by clinical and histomorphologic criteria into hyaline-vascular (HV)
      and plasma-cell (PC) subtypes. Generalized/multicentric ALNH may be divided by
      clinical criteria into generalized/multicentric ALNH without neuropathy (non
      neuropathic) and generalized/multicentric ALNH with neuropathy (POEMS-associated
      or neuropathic). The dichotomy between these two subtypes is not absolute, with
      considerable clinical overlap occurring among patients presenting with
      generalized disease. Immunophenotypic and molecular probe studies demonstrate
      clonal B-cell lymphocyte populations in some cases, particularly those with
      generalized/multicentric ALNH. However, the finding of clonal populations is of
      no value in predicting malignant clinical progression. We conclude that using
      this division of ALNH, patients presenting with symptoms and histomorphology
      consistent with ALNH can be subdivided into the appropriate category of ALNH.
      Localized or unicentric disease, either HV or PC subtype, has an excellent
      prognosis with surgery being curative in the majority of cases. Generalized or
      multicentric disease indicates a poor prognosis with short survival, with the
      neuropathic variant possessing resistance to steroids and chemotherapy and a
      corresponding worse prognosis.

PMID- 7585666
TI  - Intracranial pressure and cerebral arterial flow velocity indices in childhood
      hydrocephalus: current review.
AB  - Because of its noninvasive and repeatable nature, Doppler ultrasound has been
      increasingly used to assess changes in cerebral haemodynamics in infants and
      children with hydrocephalus. There is general agreement that a direct correlation
      exists between the intracranial pressure (from experimental, fontanometric and
      direct measurement evidence) and the resistance index. In addition, this
      increasing index has been predominantly due to a reduction in the end-diastolic
      velocity. Stable ventriculomegaly is associated with normal pulsatility. The
      cerebral blood flow velocity parameters change significantly following CSF
      drainage by tapping or shunting. The measurement of intracranial pressure and
      cerebral blood flow velocity are currently the best ways of assessing the need
      for CSF diversion and monitoring subsequent shunt function.

PMID- 7585664
TI  - The light-flash-evoked response as a possible indicator of increased intracranial
      pressure in hydrocephalus.
AB  - Surgical treatment of infantile hydrocephalus by shunt implantation may result in
      suboptimal intracranial pressure. Major neurological impairments and death are
      usually prevented by shunt treatment, but minor sequelae may persist or develop.
      The introduction of adjustable shunts has improved the possibilities of
      optimizing shunt function and minimizing the risk of such impairments. However,
      it is still impossible to determine the intracranial pressure without invasive
      measurements. Clinical findings and procedures such as computed tomography (CT)
      are not always enough to allow a conclusion as to whether a child's signs and
      symptoms are the result of suboptimal intracranial pressure (shunt dysfunction)
      or are of another etiology. With the aim of reducing the number of invasive
      pressure measurements and CT scans, we investigated the effect of increased
      intracranial pressure on the visual evoked response (VER). Binocular light flash
      stimuli of supramaximal intensity were used and VER recordings were performed
      from Oz and Cz. The VER results from a group of 31 infants and children with
      hydrocephalus and 2 children with pseudotumor cerebri were compared with
      responses from a control group of 35 healthy children. The results show that a
      subpotential, P' (P-prime), usually just preceding P1 (P100), had an increased
      latency ( > 96 ms) in all hydrocephalic children before surgery. The P' latency
      in this group was usually even above 110 ms. The latencies of other VER
      potentials were also increased but not as consistently as P'. After surgical
      intervention the VER latencies decreased and usually normalized. The P' latency
      in four children in the control group was just above the borderline latency, but
      was less than 110 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585667
TI  - Cerebrospinal fluid pulse pressure waveform analysis in hydrocephalic children.
AB  - Analysis of cerebrospinal fluid pulse pressure was reported to be useful in the
      assessment of the cerebrospinal pressure-volume compensation. The method for the
      estimation of high-frequency centroid (HFC) was modified and used to verify the
      correlation between HFC and other compensatory parameters investigated by means
      of the lumbar infusion test in 94 hydrocephalic children. The results confirm
      that in hydrocephalus HFC is positively correlated to cerebrospinal elasticity
      coefficient, but inversely to mean CSF pressure and pulse wave amplitude. It was
      also demonstrated that HFC decreased dynamically during the infusion test.

PMID- 7585665
TI  - Xenon CT measurement of cerebral blood flow in hydrocephalus.
AB  - Since the recognition of normal-pressure hydrocephalus as an entity (1965),
      ventriculo-atrial or peritoneal shunting has been proposed as a treatment for
      this disease. Unfortunately, selection of patients who would benefit from
      shunting has always been difficult, and no clinical or brain imaging criteria
      have been entirely satisfactory. Functional studies intended to measure the local
      cerebral blood flow (lCBF) seem more promising. Xenon CT CBF measurement has been
      chosen because of its ability to measure deep white matter lCBF with good spatial
      resolution. This preliminary study reports the results of lCBF measurement in
      four patients examined by this technique before and after shunting or
      cerebrospinal fluid subtraction by lumbar puncture. In this small collective the
      two patients who improved clinically after shunting or lumbar puncture also had a
      substantial improvement in deep white matter lCBF.

PMID- 7585663
TI  - Selective posterior rhizotomy for children with cerebral palsy: a 7-year
      experience.
AB  - Although selective posterior rhizotomy (SPR) was pioneered as early as 1913, only
      over the past decade has the procedure gained popular use for the treatment of
      spasticity in cerebral palsy. The medical knowledge base regarding this procedure
      is expanding, and surgical techniques continue to be revised. We present our 7
      years of experience in treating spastic cerebral palsy using SPR. The aspects of
      preoperative evaluation used by the multidisciplinary team to determine candidacy
      are outlined. The surgical procedure is detailed with a particular emphasis on
      the role of intraoperative nerve root stimulation to aid in selection for rootlet
      sectioning. Historical nerve stimulation protocols are reviewed and compared to
      our findings over the years. The functional goals are discussed in the context of
      the postoperative evaluation and therapies. Specific outcome in relation to joint
      range of motion, self care tasks, and ambulation is reported. The paper outlines
      a concise overview of our experiences and will assist the clinician in defining a
      protocol and expectations for SPR.

PMID- 7585660
TI  - Late effects of treatment in long-term survivors of cancer.

PMID- 7585668
TI  - Predictive value of brain-stem auditory evoked potentials in children with post
      traumatic coma produced by diffuse brain injury.
AB  - In the present study, brain-stem auditory evoked potentials (BAEPs) in 31
      children in post-traumatic coma with diffuse brain injury were examined. The
      BAEPs were recorded in the first 72 h after hospital admission and the findings
      of 29 patients related to the level of neurological recovery at 6 months after
      head injury. On the basis of the results, children were divided into three
      groups: the first consisted of children with bilateral and normal BAEPs (n = 19);
      the second of those with asymmetrical BAEPs (n = 6); and the third of those in
      whom BAEPs has disappeared or in whom only responses of the seventh cranial nerve
      and cochlear nucleus were recorded (n = 4). All the patients in the first group
      presented a good clinical outcome, with excellent recovery in 80%. In the second
      group three children (42.8%) had a good recovery, two (28.6%) were moderately
      disabled and one (14.3%) died of extraneurological causes. All the patients in
      the third group died. Abnormal BAEPs showed a significant correlation with
      absence of pupillary and/or corneal reflex, but not with the Glasgow Coma Score
      and anisocoria. Good statistical correlation was observed between normal BAEPs
      and visualization of basal cisterns on computed tomographic scan. The incidence
      of increased intracranial pressure was higher in patients with abnormal BAEPs,
      but the differences were not significant (P = 0.06). Our study confirms the
      predictive value of BAEPs in children's post-traumatic coma due to diffuse brain
      injury.

PMID- 7585669
TI  - Transarterial embolization of vein of Galen aneurysmal malformation after
      unsuccessful stereotactic radiosurgery. Report of three cases.
AB  - The authors present three cases of vein of Galen aneurysmal malformations (VGAMs)
      diagnosed in infancy and submitted by the referring teams for stereotactic
      radiosurgery as the initial therapy (therapeutic doses ranging between 20-25 Gy
      and 40-50 Gy to the peak dose). After the conventional follow-up of 18-24 months,
      no change could be detected in the angioarchitecture of the lesions. All three
      cases were then referred for endovascular treatment and underwent embolization by
      the transarterial route using liquid adhesives (N-butyl cyanoacrylate). This
      resulted in complete anatomical exclusion of the lesion. Regardless of the
      theoretical efficiency of radiosurgery in the management of brain arteriovenous
      malformations, the present authors believe that transarterial embolization
      remains the treatment of choice in VGAMs. It offers a high rate of morphological
      cure and the best chances for normal neurocognitive development. The time
      required by radiosurgery to achieve a significant result is too long for
      developing and maturing brain and may not prevent the negative effects of the
      lesion, mainly in regard to hemo- and hydrodynamic disorders (atrophy,
      subcortical calcifications, etc.) created by the VGAM, thus leading to
      irreversible mental retardation.

PMID- 7585671
TI  - Cerebellar dermoid tumor and occipital meningocele in a monozygotic twin: clues
      to the embryogenesis of craniospinal dysraphism.
AB  - A case of monochorionic/monoamnionic twin with discordant occipital developmental
      malformations is presented. One female twin appeared to have an occipital
      meningocele with cerebellar aplasia and died immediately after birth. The other
      twin presented with signs and symptoms of raised intracranial pressure at the age
      of 7 months. Severe hydrocephalus was present due to an infected intracerebellar
      dermoid tumor with a contiguous occipital dermal sinus. The clinical and
      pathological characteristics are described and the different theories concerning
      twinning, embryogenesis, and dysmorphology in relation to neural tube defects are
      discussed. Analysis of the features of these monozygotic twins indicates that a
      meningocele is not a post-neurulation disorder but results from deficient
      neurulation, probably due to mesodermal insufficiency.

PMID- 7585673
TI  - Ammar shunt: an option to overcome shunt complications in premature and term
      neonates.
AB  - It has been hypothesized, and generally accepted, that the final outcome of the
      treatment of hydrocephalus is to a great extent related to the earliness of
      intervention and treatment. However, there is special concern regarding the
      higher risk of infection and shunt malfunctions in neonates as compared with
      older infants. Therefore, two new shunt systems have been designed specifically
      to tip the balance in favor of early shunting. The first shunt is made for
      premature neonates and the second for neonates in general. The general
      characteristics of these two shunts are: (1) the entire shunt is a low-pressure
      valve, with double distal slit valves; (2) the shunts are made of soft silicon
      material; (3) they are of very small configuration, without any compressing
      elements which may lead to skin necrosis over the shunt; (4) no metal has been
      used in them, so they are MRI compatible.

PMID- 7585672
TI  - A method for continuous external drainage in the management of infantile subdural
      collections.
AB  - There is no consensus on the management of infantile chronic subdural
      collections. Subdural tapping, craniotomy and removal of membranes, and shunting
      from the subdural space have all been used. We performed continuous external
      subdural drainage (CESD) as a step prior to subdural-peritoneal shunt placement
      in the management of infantile chronic subdural fluid collections. A lumbar
      drainage set was used for CESD. The catheter was placed in the subdural space
      through the anterior fontanel with a Touhy needle. This percutaneous technique
      seems an easy and safe method for CESD in infants with chronic subdural
      collections.

PMID- 7585670
TI  - Intracranial ependymomas in childhood: a report of 24 cases followed for 5 years.
AB  - The management and outcome of 24 patients with intracranial ependymomas admitted
      to our institution between January 1979 and May 1988 have been analysed. Four
      patients out of the ten with infratentorial ependymomas who underwent a visible
      total resection were alive and free of disease at 5 years, whereas all those who
      had had an incomplete resection were dead. The prognosis in the supratentorial
      group was worse; only one patient out of seven was alive and free of disease at 5
      years. Nine patients (six infratentorial and three supratentorial ependymomas)
      were investigated with myelography for occult spinal metastases, and apart from
      one who had a direct extension of an infratentorial tumour into the upper
      cervical spine, none had detectable metastases. Eight patients with
      infratentorial tumours underwent a ventriculo-peritoneal shunt insertion, and in
      three of them this followed a visible total resection of the tumour. Comparison
      of our results with those from other series suggests that any improvement in
      outlook is related primarily to an increased number of children surviving their
      initial surgical treatment, rather than to better methods of postoperative tumour
      control.

PMID- 7585674
TI  - Dermoid cyst of the frontal bone away from the anterior fontanel.
AB  - A case with a midline dermoid cyst of the frontal bone away from the anterior
      fontanel is reported. Although a few such cases have been reported, detailed
      descriptions are not given. Possible intracranial extension of these lesions is
      discussed with review of the pertinent literature.

PMID- 7585675
TI  - Proximal migration and subcutaneous coiling of a peritoneal catheter: report of
      two cases.
AB  - The authors report two cases with a rare complication of ventriculoperitoneal
      shunt. The peritoneal catheters migrated upward to the scalp and to the
      clavicular area. In one case, the whole length of the peritoneal catheter was
      pulled out from the peritoneal cavity and was coiled subcutaneously. Both of the
      patients had the habit of head rotation and one of the patients had a history of
      subcutaneous fluid collection at the site of coiling. At surgery, whitish
      inflammatory granulation tissues were noted around the catheter in both cases,
      which might act as an anchoring point for the "windlass effect".

PMID- 7585676
TI  - Infarction of the territory supplied by the contralateral superior cerebellar
      artery in a case of descending transtentorial herniation.
AB  - Infarction of the territory supplied by the contralateral superior cerebellar
      artery in cases of descending transtentorial herniation has not been reported.
      The authors experienced a primitive neuroectodermal tumor in a patient whose
      consciousness deteriorated transiently due to descending transtentorial
      herniation. On the magnetic resonance imaging taken 8 days after the herniation,
      lesions thought to be infarction of territories supplied by the ipsilateral
      posterior cerebral artery and the contralateral superior cerebellar artery were
      noted. The possible mechanism of this peculiar pattern of infarction is
      discussed.

PMID- 7585678
TI  - Radiotherapy in the treatment of low-grade astrocytomas. I. A survival analysis.
AB  - Between 1954 and 1986 inclusive, 160 children in the North West Region of England
      were registered with histologically proven lowgrade astrocytomas (grade 1 or 2).
      Ten died before receiving any treatment, and a further seven died within 28 days
      of surgery, leaving 143 children whose survival in relation to treatment modality
      is the subject of this paper. Low-grade astrocytomas are responsive to radiation
      therapy. This treatment has no clear benefit to offer children with superficial
      tumours that can be resected completely or nearly so, but significantly improves
      survival rates when tumours are deep-seated and not amenable to excision.

PMID- 7585680
TI  - Ventriculoperitoneal shunts for hydrocephalus: a focus group discussion on the
      selection of shunt systems in pediatrics. A report of the Pediatric Neurosurgery
      Research Group meeting, December 1992.
AB  - As part of the Continuing Quality Improvement Study, phase I, 12 pediatric
      neurosurgeons participated in a discussion group to respond to the various issues
      related to selection of ventriculoperitoneal shunt systems in their practice. It
      was estimated that between then all the 12 participants performed approximately
      1200 shunt procedures per year in the USA. The data were analyzed by grid and
      fish-bone charts as part of the data collection. All 12 participants indicated
      that they preferred a reservoir in the shunt system, 8 of them indicating that
      they preferred this for a manual test of the system. Three indicated that they
      did not routinely manipulate the system for testing. One participant stated that
      he placed a reservoir within the shunt system primarily to prevent migration of
      the ventricular catheter. Nine neurosurgeons indicated that they employed cranial
      valves in their shunt systems, and three indicated that they employed slit-end
      peritoneal catheters only. In reference to Delta valves, nine participants
      indicated that they employed them on occasions. In reference to pressure in the
      valve system, one participant employed high-pressure valves at all times, five
      employed only medium-pressure systems, and the remaining six always employed low
      pressure valves. All 12 neurosurgeons stated that the incidence of symptomatic
      slit ventricle in their practices was between 1% and 5%, in their mind
      irrespective of the system used. It was concluded that any form of
      ventriculoperitoneal shunt, with or without valves, with slit-end valves or
      cranial valves seemed to work equally well in the hands of a dedicated pediatric
      neurological surgeon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585681
TI  - Myotonic dystrophy in a large Sicilian kinship: a case report.
AB  - A large Sicilian kinship in which myotonic dystrophy (DM) affected spanning four
      generations is presented. The pedigree clearly illustrates the phenomenon of
      anticipation, and illustrates that this phenomenon is more marked when
      transmission occurs through an affected female rather than an affected male. The
      pedigree is interpreted in light of recent genetic advances in DM. Neurosurgeons
      and neurologists should consider a diagnosis of DM when asked to evaluate a
      floppy infant with enlarged lateral ventricles, and should be aware of special
      features regarding its inheritance pattern.

PMID- 7585679
TI  - Radiotherapy in the treatment of low-grade astrocytomas. II. The physical and
      cognitive sequelae.
AB  - The purpose of the present study was to define the late effects, both physical
      and psychological, of treating low-grade astrocytomas with radiotherapy. Fifty
      patients, half of whom received radiotherapy, underwent an assessment of
      neurological and neuropsychological function. There was no difference in
      neurological function between the two groups. The radiotherapy recipients,
      including those with cerebellar tumours, performed significantly worse on
      measures of intelligence and information processing. In addition, there was a
      greater incidence of special education needs in the irradiated group. We conclude
      that children with low-grade astrocytomas who receive radiotherapy have no
      greater neurological deficit but that the use of radiotherapy carries a penalty
      in terms of long-term cognitive function and confirmed the findings of many
      previous reports that supratentorial irradiation is detrimental. More
      surprisingly, it has been demonstrated that local field irradiation to the
      posterior fossa can also produce significant cognitive impairment.

PMID- 7585682
TI  - Familial neurofibromatosis 1 with germinoma involving the basal ganglion and
      thalamus.
AB  - Intracranial germinoma associated with neurofibromatosis 1 (NF-1) has never been
      documented previously. We report a case of familial NF-1 with a germinoma
      involving the right basal ganglion and thalamus. A 12-year-old boy presented with
      multiple cafe-au-lait spots and a family history of neurofibromatosis in his
      mother, one of two siblings, and his maternal grandfather. His intracranial
      lesion was subtotally resected. Histologically, it was a pure germinoma. Serum
      alpha-feto protein and beta-human chorionic gonadotropin levels were within the
      normal range. Postoperative myelographic examination and cerebrospinal fluid
      cytology study showed no evidence of subarachnoid seeding. The patient received
      postoperative combination chemotherapy resulting in complete response and
      clearance of the residual tumor. Although this finding of an intracranial
      germinoma in a patient with familial NF-1 may be coincident, it is suggestive of
      a potential genetic predisposition. Longitudinal evaluation for the possibility
      of neoplasm, especially germ cell tumor, in basal ganglion lesions in NF-1
      patients is necessary.

PMID- 7585683
TI  - Infantile subdural fluid collection: diagnosis and postoperative course.
AB  - The authors reviewed 47 cases of infantile subdural fluid collection with regard
      to diagnosis and postoperative course after placement of a subdural-peritoneal
      shunt. CT scan with contrast enhancement proved to be an important diagnostic
      modality, showing vessels in the subarachnoid space as high-density spots.
      Utilizing this technique, we were able to differentiate the following varieties
      of fluid collection: (1) subdural fluid collection, in which enhancing vessels
      were seen on the brain surface, (2) subarachnoid fluid collection, in which
      vessels were on the inner table of the cranium, and (3) coexistence of subdural
      and subarachnoid fluid collections, in which vessels were between the inner table
      of the cranium and the brain surface. The postoperative course of subdural fluid
      collection was characterized as follows: (1) the subdural fluid collection
      decreased first, with increased subarachnoid fluid collection; (2) the
      subarachnoid fluid collection remained after the disappearance of subdural fluid
      collection; and (3) the brain expanded again later. Subdural fluid collection
      disappeared about 1 month after the shunt operation, which could lead occlusion
      of the shunt system. Postoperative enlargement of the subarachnoid space was an
      early indicator of the efficacy of the subdural-peritoneal shunt.

PMID- 7585677
TI  - Clival chordoma in early childhood.

PMID- 7585684
TI  - Assessment of mortality associated with mild head injury in the pediatric age
      group.
AB  - Reducing mortality among accident and trauma patients requires careful attention
      to monitoring those regarded as being at low risk. We hospitalized almost 1600
      head-injured patients in the period between 1979 and 1992 at the Neurosurgery
      Department of Gazi University Medical School, Ankara, Turkey. These patients were
      selected from among the numerous patients admitted to our emergency unit and
      treated with the same protocol in the same department. Among the hospitalized
      children, there were three patients defined as having a mild head injury on the
      basis of Glasgow Coma Scale scores of 15 who later had unfavorable outcomes.
      Clinical signs that might identify potentially endangered patients with mild
      injury were gathered; these included the presence of post-traumatic amnesia,
      somnolence, irritability, anisocoria, local evidence of trauma to the head,
      associated injuries, history of altered consciousness, and skull fracture. The
      study was designed to identify features by which patients who are in real danger
      can be distinguished among the many with trivial trauma that we face every day.
      We did not find any identifying clinical features and concluded that computed
      tomographic scanning is the only reliable answer. This will reduce avoidable
      mortality and morbidity by identifying the patients who are at higher risk than
      is at first evident.

PMID- 7585685
TI  - Effects of carbamazepine and valproate on brainstem auditory evoked potentials in
      epileptic children.
AB  - Brainstem auditory evoked potentials (BAEPs) were recorded in 18 epileptic
      children receiving carbamazepine and 10 epileptic children receiving valproate.
      BAEPs were recorded before the administration of antiepileptic drugs (AEDs) and
      13 months later during which the children received AEDs. Statistical analysis of
      peak latencies and interpeak intervals of waves I-III-V were made. Carbamazepine
      treatment resulted in prolongation of peak latencies of waves I-III-V and
      interpeak intervals I-III and I-V. Valproate monotherapy, on the other hand,
      caused no consistent changes on BAEP. On the basis of these results we suggest
      that chronic carbamazepine therapy exerts a suppressive influence on the auditory
      pathways, both peripherally at the level of the cochlea and/or auditory nerve,
      and centrally at the brainstem.

PMID- 7585688
TI  - Treatment of hydrocephalus in patients with meningomyelocele or encephalocele: a
      recent series.
AB  - Meningomyelocele/encephalocele with associated ventriculomegaly can be treated as
      a single-stage procedure (i.e., both lesions treated simultaneous) or as two
      stage procedures (i.e., each lesion treated at a separate time). A delay in
      closure of the meningomyelocele/encephalocele is associated with a higher
      incidence of ventriculitis/ventricular shunt infection-particularly when closure
      is performed more than 36 h after birth. In these situations, closure followed by
      surveillance cultures, appropriate antibiotics, ventricular drainage, and then
      delayed ventricular shunting seems more reasonable.

PMID- 7585686
TI  - Neuroimaging and functional examination in hydrocephalus: a comment.
AB  - All the papers were of a high scientific standard, giving us clearly defined
      information that will be applicable in the diagnosis and further management of
      infantile hydrocephalus. Particularly interesting subjects were the comparison of
      CT and MRI in the evaluation of hydrocephalus and cine MRI, which allows
      evaluation of the CSF dynamic flows. CBF measurements with xenon CT/CBF imaging
      or transcranial Doppler examinations of CBF velocity are used much more for
      evaluation of the shunt indications for shunting and also for definition of the
      outcome of shunting procedures. Although measurements of physiological CSF
      parameters are important, studies on the pathophysiology of hydrocephalus should
      be focused on the changes in CBF in hydrocephalus patients. The key points and
      conclusions presented by each author are discussed and the prospects mentioned
      for the future in neuroimaging and functional examination in hydrocephalus.

PMID- 7585687
TI  - Intraoperative monitoring of cerebral blood flow during ventricular shunting in
      hydrocephalic pediatric patients.
AB  - Several studies have demonstrated lowered cerebral blood flow (CBF) in patients
      with hydrocephalus and symptoms of raised intracranial pressure. Ventricular
      shunting in such cases permits a sudden increase in CBF. The pathophysiology of
      functional brain deficit secondary to hydrocephalus is little understood.
      Improvement of the patient's clinical status after drainage of CSF suggests that
      cerebral dysfunction is not necessarily due to permanent brain damage. In fact,
      it improves rapidly after ventricular taps. In view of this it would be helpful
      to monitor cerebral perfusion. The transcranial Doppler (TCD) ultrasonography
      technique allows real-time monitoring of the intracranial circulation and makes
      it possible to evaluate the physiopathological correlation between ventricular
      dilatation and CBF. Continuous monitoring of the middle cerebral artery (MCA) by
      TCD was performed in three hydrocephalic children (2 months, 14 months, and 8
      years old) during a ventricular-peritoneal shunt operative procedure. A TC-2000S
      device provided by an IMP-F fixed probe was utilized. In all patients, when the
      lateral ventricle was shunted and the CSF could flow away, a clear and sudden
      increase of flow velocity above 30% was detected. The pulsatility index (PI) was
      also pathologically increased in all patients. A gradual normalization of this
      index was revealed after the shunting procedure. Our experience has to be
      considered preliminary, but nonetheless, it suggests a clear correlation between
      hydrocephalic disease and concomitant CBF alterations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7585689
TI  - Shunt-valve noise as an unusual reason for shunt revision.
AB  - A 29-year-old male patient suffering from communicating hydrocephalus was treated
      by placement of a ventriculoatrial shunt (Pudenz-Heyer bur-hole valve). A
      disturbingly loud, pulse-synchronous, bruit in the ear on getting up from lying
      down remained unrecognized for 3 years as possibly generated by air bubbles in
      the valve. Clinical and technical investigations by a phonocardiographic and a
      transcranial Doppler device demonstrated that the noise was a functional
      indicator of shunting activity, relying on intracranial pressure conductional on
      arterial blood pressure as determined by its close relationship to the cardiac
      cycle. When this phenomenon was looked for, it was detected in three other
      patients, one of whom saw it as a shunt-function indicator.

PMID- 7585690
TI  - Intraventricular blood after "traumatic" lumbar puncture: a report of two cases.
AB  - Blood was detected in the lateral ventricles on head computed tomograms performed
      after "traumatic" lumbar punctures in two children. This finding has not
      previously been observed or reported. The likely mechanisms by which blood from
      the spinal thecal sac reached the ventricles are discussed. This potentially
      confusing observation, if not correctly accounted for, may lead to an
      unnecessary, fruitless search for the site of a supposed "primary"
      intraventricular haemorrhage.

PMID- 7585691
TI  - Endovascular treatment of an infantile nongalenic cerebral arteriovenous fistula
      with cyanoacrylate.
AB  - We report the radiological features, including Doppler sonography and magnetic
      resonance angiography (MRA) findings, of a nongalenic arteriovenous fistula
      diagnosed in the neonatal period. Hypertensive hydrocephalus developed in
      infancy. Emergent percutaneous transarterial embolization with n-butyl-2
      cyanoacrylate was successfully performed and lead to clinical improvement. MRA
      allowed a noninvasive follow-up.

PMID- 7585692
TI  - Hemangioblastoma of the IV ventricle.
AB  - A case of solid hemangioblastoma in the IV ventricle in a 16-year-old boy is
      reported because of the rarity of this type of lesion. Microsurgical removal of
      the lesion was accomplished without any side effects in this highly vascular
      tumor in a strategic location.

PMID- 7585693
TI  - A total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x) sequence.

PMID- 7585694
TI  - Total synthesis of sulfated Le(a) pentaosyl ceramide.

PMID- 7585695
TI  - Circular dichroism of the O-specific polysaccharide of Vibrio cholerae O1 and
      some related derivatives.
AB  - The O-specific polysaccharide (O-SP) of Vibrio cholerae O1 is a homopolymer of
      alpha-(1 --> 2)-linked 4-amino-4, 6-dideoxy-D-mannopyranose whose amino group is
      acylated with 3-deoxy-L-glycero-tetronic acid [N-(3-deoxy-L-glycero- tetronyl)
      alpha-D-perosamine]. The circular dichroism (CD) of the O-SP as well as of a
      number of N-acyl (formyl, acetyl, 4-hydroxybutyl, 3-deoxy-L-and D-glycero
      tetronyl) derivatives of methyl alpha-glycosides of 4-amino-4,6-dideoxy-D
      mannopyranose (methyl alpha-D-perosaminide) has been studied for solutions in
      water, acetonitrile and 1,1,1-trifluoroethanol. The strong solvent dependence of
      the sign and intensity of the CD observed for the monosaccharide amides bearing
      achiral acyl groups is explained by solvent-mediated change of the orientation of
      the amido group relative to the proximal hydroxyl group at C-3. A change in the
      population of the nonplanar conformers with a pyramidal arrangement of bonds at
      the amido nitrogen has also been considered. The effect of solvents upon the CD
      spectra of compounds bearing chiral N-acyl substituents is less pronounced than
      that of their counterparts bearing achiral N-acyl substituents. The sign of the
      CD for the O-SP was found negative in all solvents used. This result is in
      agreement with the negative sign of the CD of the n --> pi electron transition
      observed, independent of the solvent, for the monosaccharide derivative
      containing the L-glycero-3-deoxytetronamido group, and the positive sign found
      for its D-glycero-counterpart.

PMID- 7585696
TI  - Enzymatic synthesis of mannobioses and mannotrioses by reverse hydrolysis using
      alpha-mannosidase from Aspergillus niger.
AB  - Various manno-oligosaccharides including alpha-D-man-(1 --> 2)-D man and alpha-D
      man-(1 --> 2)-alpha-D-man-(1 --> 2)-D-man were formed when a highly concentrated
      mannose solution was incubated in the presence of alpha-mannosidase from
      Aspergillus niger. alpha-D-Man-(1 --> 2)-D-man and alpha-D- man-(1 --> 2)-alpha-D
      man-(1 --> 2)-D-man were isolated by activated carbon chromatography followed by
      high performance liquid chromatography using an amino-silica column. In addition
      to the above oligosaccharides, alpha-D-man-(1 --> 3)-D-man, alpha-D-man-(1 --> 6)
      D-man, and alpha-D-man-(1 --> 2)-alpha-D-man-(1 -->6)-D-man were also isolated.

PMID- 7585697
TI  - Utility of non-covalent complexes in the matrix-assisted laser desorption
      ionization mass spectrometry of heparin-derived oligosaccharides.
AB  - Molecular weights of heparin-derived oligosaccharides ranging from disaccharides
      to hexadecasaccharides have been determined by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry. While these compounds ionize poorly
      or not at all when used as such, a strong signal can be obtained of their ionic
      complexes formed with a basic peptide or protein. The molecular weight of the
      sulfated oligosaccharide is determined by subtracting the mass of the basic
      component from that of the complex. Optimization of the experimental conditions
      resulted in sub-picomole sensitivity, in the elimination of sulfate loss and of
      the interference from attachment of inorganic cations. Synthetic peptides (Arg
      Gly)10 and (Arg-Gly)15 were specifically designed as complexing agents for
      synthetic and natural heparin fragments up to decasaccharides. Accurate molecular
      weight determination on chemically homogeneous oligosaccharides (+/- 0.05%)
      unambiguously identified the number of saccharide units, and the number of O,N
      sulfate and N-acetyl groups. For oligosaccharides larger than decasaccharides, a
      small basic protein, angiogenin (M(r) = 14,120), was used to form the complex (an
      inhomogeneous hexadecasaccharide fraction was the largest available for this
      study). For inhomogeneous samples larger than decasaccharides, the mass accuracy
      is lower (+/- 0.2-0.3%) but still suffices to determine the number of saccharide
      units present and to estimate the number of sulfate groups, except it is no
      longer possible to differentiate one sulfate from two N-acetyl groups (delta = 4
      Da). However, taking into account known regularities of sulfation and
      acetylation, the specificity of heparin lyases and chemical degradation steps,
      the method promises to contribute significantly to the determination of the
      primary structure of heparin and other sulfated glycosaminoglycans.

PMID- 7585698
TI  - Preparation of alpha -and beta-dienyl glycosides used as dienes in aqueous Diels
      Alder reactions. Influence of the carbohydrate moiety on the thermodynamics of
      the reaction.
AB  - A series of 1,3-butadienyl glycosides (mono- and di-saccharides) have been
      prepared and the kinetics of their Diels-Alder reaction with buten-2-one in water
      have been studied. The activation parameters for these aqueous cycloadditions
      provide clues for the hydration structure of such glyco-organic compounds.

PMID- 7585699
TI  - Structure of an acidic microcapsular glycan from the reference strain (C.D.C. 866
      57) for Serratia marcescens serogroup O1.
AB  - The structure of the acidic polysaccharide from Serratia marcescens serogroup O1
      has been investigated. NMR spectroscopy together with sugar and methylation
      analysis have been used as well as a uronic degradation. The polysaccharide
      consists of pentasaccharide repeating units having the following structure.
      (sequence see text) The polysaccharide also contains one equivalent of O-acetyl
      groups per repeating unit present on, inter alia, a hydroxymethyl group.

PMID- 7585700
TI  - Characterisation of the endo-polygalacturonase-resistant region of the pectin
      from Bupleurum falcatum L.--a polysaccharide with an active function in clearance
      of immune complexes.

PMID- 7585702
TI  - Stereoselective synthesis of O-serinyl/threoninyl-2-acetamido-2-deoxy-alpha- or
      beta-glycosides.
AB  - General glycosidation methodology has been developed which can selectively
      provide 2-acetamido-2-deoxy-alpha- or beta-glycosides of beta-hydroxy-alpha-amino
      acid derivatives [glucopyranoside-(8, 43), galactopyranoside- (9, 13),
      mannopyranoside- (10), lactoside analogs (11, 38) and 3-O-beta-galactopyranosyl
      mannopyranoside (12)] stereoselectively in excellent yield from the highly
      nucleophilic alpha-imino esters (Schiff bases) of L-serine and L-threonine.
      Various glycosides were converted via their amino and acetamido derivatives to
      Fmoc-protected serinyl- or threoninyl-glycosides (24-28, 37, 41, 46) which are
      all suitable building blocks for the solid-phase synthesis of O-glycopeptides.
      Complete 1H- and 13C-NMR data are provided for all compounds.

PMID- 7585701
TI  - Conformational flexibility in highly sulfated beta-D-glucopyranoside derivatives.
AB  - Triggered by findings on heparin-like disaccharides, the conformation of sulfated
      glucopyranosides was investigated. Sodium (methyl 2,3,4-tri-O-sulfonato-beta-D
      glucopyranosid)uronate tetrasodium salt is in a conformational equilibrium, to
      which a non-chair conformation contributes. The same is true for methyl (methyl
      2,3,4-tri-O-sulfonato-beta-D-glucopyranosid)uronate trisodium salt, methyl
      2,3,4,6-tetra-O-sulfonato-beta-D-glucopyranoside tetrasodium salt, and octa-O
      sulfonato-beta, beta-trehalose octasodium salt, with less obvious non-chair
      contributions. The effect is charge related. The conformational effect, which
      does not occur in analogous alpha-D-glucopyranoside derivatives, is discussed in
      terms of the anomeric effect.

PMID- 7585703
TI  - Syntheses and testing of substrates and mechanism-based inactivators for
      xylanases.
AB  - The syntheses of the 2,5- and 3,4-dinitrophenyl beta-xylobiosides by two separate
      routes are described, as well as the syntheses of the 2,4-dinitrophenyl beta
      glycosides of 2-chloro-2-deoxy-xylobiose and 2-deoxy-2-fluoro-xylobiose. Both the
      3,4- and 2,5-dinitrophenyl beta-xylobiosides proved to be good substrates for the
      Bacillus subtilis xylanase, with kcat/Km values of 1.0 and 34.4 mM-1 s-1,
      respectively. Excellent time-dependent inactivation of the exoxylanase/glucanase
      from Cellulomonas fimi was provided by 2,4-dinitrophenyl 2-deoxy-2-fluoro-beta
      xylobioside, according to inactivation parameters of ki = 0.057 min-1 and Ki =
      0.0035 mM.

PMID- 7585704
TI  - Synthesis of sialyl Lewis X ganglioside analogues containing modified L-fucose
      residues.
AB  - Sialyl Le(x) ganglioside analogues containing 2-epi-, 2,3-di-epi-, 4-epi-, and 2
      O-methyl-L-fucose in place of the L-fucose residue have been synthesized.
      Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy
      beta-D-glucopyranosyl)-(1-->3)- 2,4,6- tri-O-benzyl-beta-D-galactopyranoside with
      the methyl 1-thioglycoside derivatives of the respective fucose analogues, using
      dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the
      corresponding protected 2-(trimethylsilyl)ethyl deoxy-alpha-L-hexopyranosyl-(1-
      >3)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-beta-D-galactopyrano
      sid es. These were transformed by reductive ring-opening of their benzylidene
      acetal groups into the glycosyl acceptors. Dimethyl (methylthio)sulfonium
      triflate-promoted glycosylation of these compounds with methyl O-(methyl 5
      acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2-
      nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D-
      galactopyranoside afforded the desired pentasaccharides, which were converted via
      reductive removal of their benzyl groups, O-acetylation, selective removal of the
      2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the
      corresponding alpha-tri-chloroacetimidates. Glycosylation of (2S,3R,4E)-2-azido-3
      O-benzoyl-4-octadecene-1,3-diol these in the presence of boron trifluoride
      etherate afforded the expected beta-glycosides, which were transformed in good
      yields, via selective reduction of the azido group, coupling with octadecanoic
      acid, O-deacylation, and deesterification, into the target gangliosides. The 2
      (trimethylsilyl)ethyl glycosides of sialyl Le(x) oligosaccharides containing
      modified fucose were also prepared from the intermediates of the ganglioside
      synthesis.

PMID- 7585705
TI  - Synthesis of carbocyclic analogues of the mannosyl trisaccharide: ether- and
      imino-linked methyl 3,6-bis(5a-carba-alpha-D-mannopyranosyl)-3,6-dideoxy-alpha-D
      mannopyran osides.
AB  - Carbocyclic analogues 2 and 3 of the "trimannosyl structure 1", methyl 3,6-bis(5a
      carba-alpha-D-mannopyranosyl)-3,6-dideoxy-alpha-D-ma nnopyranosides bonded by way
      of respective ether and imino linkages, were synthesized. The ether 2 had no
      inhibitory activity against alpha-D-mannosidase; in contrast, the imino compound
      3 was a mild inhibitor. Furthermore, the inhibitory activity of 4, related to 3
      by introduction of unsaturation between C-5 and C-5a of the carba-sugar moieties,
      was shown to be somewhat greater.

PMID- 7585706
TI  - New syntheses of D-tagatose and of 1,5-anhydro-D-tagatose from D-galactose
      derivatives.
AB  - 3,4-O-Isopropylidene-D-lyxo-hexopyranosid-2-ulose derivatives, obtained by
      oxidation of 3,4,6-protected D-galactopyranosides, can be alkylated in their
      anionic 2,6-pyranose forms to produce bis-glycosides containing the 2,5
      dioxabicyclo[2.2.2]octane ring system. The 1-benzyl-2-methyl bis-glycoside 4b,
      when subjected to catalytic hydrogenolysis, produces the methyl D-lyxo
      hexopyranos-2-uloside 10, existing as an 8:2 mixture of 1,5-pyranose anomers 9.
      Computational and NMR evidence is presented in favour of the hypothesis that the
      major anomer has the alpha configuration. Reduction of 9/10 with NaBH4 gives
      methyl 3,4-O-isopropylidene-beta-D-tagatopyranoside, that can be hydrolyzed to D
      tagatose. A simple synthesis of 1,5-anhydro-D-tagatose, starting from 1,5-anhydro
      D-galactitol, is also presented. All new compounds were fully characterized by
      elemental analysis and by 1H and 13C NMR spectroscopy.

PMID- 7585707
TI  - Synthesis of specifically deoxygenated disaccharide derivatives of the Shigella
      dysenteriae type 1 O-antigen.
AB  - The synthesis of methyl O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-D
      galactopyranosides specifically deoxygenated at position 2 (31), or 4 (21) of the
      rhamnopyranosyl residue was accomplished using methyl 3,4,6-tri-O-benzoyl-alpha-D
      galactopyranoside (18) as the glycosyl acceptor. Phenyl thionocarbonate
      activation of the penta-O-benzoylated disaccharide precursor followed by Barton
      reduction and Zemplen transesterification gave 31, while 21 was obtained via
      condensation of the deoxygenated monosaccharide donor with 18, and subsequent
      debenzoylation of the product.

PMID- 7585708
TI  - Structural studies on a cell wall polysaccharide from Bifidobacterium longum
      YIT4028.
AB  - The major fraction of rhamnogalactan was isolated from the cell wall of
      Bifidobacterium longum YIT4028 by treatment with N-acetylmuramidase. This
      polysaccharide was composed of rhamnose and galactose in a molar ratio of about
      2:3. The 13C NMR spectrum indicated that it contained a pentasaccharides
      repeating unit. This observation, and the results of Smith degradation, partial
      acid hydrolysis and methylation analysis led to the conclusion that its structure
      is [formula: see text]

PMID- 7585709
TI  - A mild and efficient procedure to remove acetal and dithioacetal protecting
      groups in carbohydrate derivatives using 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone.

PMID- 7585710
TI  - Towards the synthesis of sialic acid-based Salmonella typhimurium sialidase
      inhibitors.

PMID- 7585711
TI  - Synthesis of 4-methylumbelliferyl-beta-D-glucan oligosaccharides as specific
      chromophoric substrates of (1-->3), (1-->4)-beta-D-glucan 4-glucanohydrolases.

PMID- 7585712
TI  - Authentic standards for the reductive-cleavage method. The positional isomers of
      partially methylated and acetylated or benzoylated 1,4-anhydro-D-xylitol.
AB  - Described herein is a general method for the synthesis of all positional isomers
      of methylated and acetylated or benzoylated 1,4-anhydro-D-xylitol. The benzoates
      are generated simultaneously from 1,4-anhydro-D-xylitol by sequential partial
      methylation and benzoylation or sequential partial benzoylation and methylation.
      The individual isomers are obtained in pure form by high-performance liquid
      chromatography. Debenzoylation and acetylation provided the corresponding
      acetates. The 1H NMR spectra of the benzoates and the electron ionization mass
      spectra of the acetates and the tri-O-methyl derivative are reported herein as
      are the linear temperature programmed gas-liquid chromatography retention indices
      of the acetates and the tri-O-methyl derivative on three different capillary
      columns.

PMID- 7585714
TI  - Authentic standards for the reductive-cleavage method. The positional isomers of
      partially methylated and acetylated or benzoylated 1,5-anhydro-D-mannitol.
AB  - Described herein is an efficient method for the synthesis of the sixteen
      positional isomers of methylated and acetylated or benzoylated 1,5-anhydro-D
      mannitol. The compounds are generated simultaneously by partial methylation of
      1,5-anhydro-D-mannitol and subsequent benzoylation, and the individual isomers
      are obtained in pure form by high-performance liquid chromatography.
      Debenzoylation of the latter and acetylation yielded the desired acetates. The
      the benzoates and the electron-ionization mass spectra of the acetates and the
      tetra-O-methyl derivative are reported herein as are the linear temperature
      programmed gas-liquid chromatography retention indices of the acetates and the
      tetra-O-methyl derivative on three different capillary columns.

PMID- 7585715
TI  - Authentic standards for the reductive-cleavage method. The positional isomers of
      partially methylated and acetylated or benzoylated 1,5-anhydro-D-glucitol.
AB  - Described is an efficient method for the synthesis of the sixteen positional
      isomers of methylated and acetylated or benzoylated 1,5-anhydro-D-glucitol. The
      compounds are generated simultaneously by partial methylation of 1,5-anhydro-D
      glucitol and subsequent benzoylation, and the individual isomers are obtained in
      pure form by high-performance liquid chromatography. Debenzoylation of the latter
      and acetylation yielded the desired acetates. Reported are the 1H NMR spectra of
      the benzoates and the electron-ionization mass spectra of the acetates and the
      tetra-O-methyl derivative. Also reported for the acetates and the tetra-O-methyl
      derivative are their linear temperature programmed gas-liquid chromatography
      retention indices on three different capillary columns.

PMID- 7585716
TI  - Synthesis and characterization of authentic standards for the analysis of
      ribofuranose-containing carbohydrates by the reductive-cleavage method.
AB  - Described herein is the synthesis of  all positional isomers of partially
      methylated and acetylated or benzoylated 1,4-anhydro-D-ribitol. The benzoates are
      generated simultaneously from 1,4-anhydro-D-ribitol by sequential partial
      methylation and benzoylation or sequential partial benzoylation and methylation.
      The individual isomers are obtained in pure form by  high-performance liquid
      chromatography. Debenzoylation and acetylation provided the corresponding
      acetates. Reported herein are the 1H NMR spectra of the benzoates and the
      electron-ionization mass spectra of the acetates and the tri-O-methyl derivative
      and also for the acetates and the tri-O-methyl derivative, their linear
      temperature programmed gas-liquid chromatography retention indices on three
      different capillary columns.

PMID- 7585717
TI  - Separation of cyclodextrins and their derivatives by thin-layer and preparative
      column chromatography.
AB  - Cyclodextrins, their derivatives and products of their partial hydrolysis are
      clearly separated by chromatography on silica gel by mobile phases containing
      aqueous ammonia and organic solvent (acetonitrile or 1-propanol). This system
      allows separation of compounds with different numbers of substituents on
      cyclodextrin, but does not allow the separation of isomers; the system can be
      used both for thin-layer chromatography and for preparative column
      chromatography. The isomers in the fraction thus obtained can be in some cases
      separated, after peracetylation, by chromatography on silica gel using a mobile
      phase consisting of methanol and dichloromethane. This chromatographic sequence
      potentially yields derivatives of cyclodextrins in quantities which enable
      evaluation of their solubilization and biological properties.

PMID- 7585713
TI  - Synthesis and characterization of authentic standards for the reductive-cleavage
      method. The positional isomers of partially methylated and acetylated or
      benzoylated 1,4-anhydro-L-fucitol.
AB  - Described herein is the synthesis of all positional isomers of methylated and
      acetylated or benzoylated 1,4-anhydro-L-fucitol. The benzoates are generated
      simultaneously from 1,4-anhydro-L-fucitol by sequential partial methylation and
      benzoylation or sequential partial benzoylation and methylation. The individual
      isomers are obtained in pure form by high-performance liquid chromatography.
      Debenzoylation and acetylation provided the corresponding acetates. The 1H NMR
      spectra of the benzoates and the electron-ionization mass spectra of the acetates
      and the tri-O-methyl derivative are reported herein as are the linear temperature
      programmed gas-liquid chromatography retention indices of the acetates and the
      tri-O-methyl derivative on three different capillary columns.

PMID- 7585721
TI  - The structure of the O-specific polysaccharide chain of Proteus penneri strain 42
      lipopolysaccharide.

PMID- 7585720
TI  - Complete assignments of 13C NMR resonances to all the carbon atoms of the
      trimannosido-di-N-acetylchitobiosyl structure in a pentaantennary decasaccharide
      glycopeptide.

PMID- 7585719
TI  - Structure of the capsular polysaccharide from Alteromonas sp. CMM 155.
AB  - Capsular polysaccharide (CPS) was obtained by water-saline extraction of the
      Alteromonas sp. CMM 155. On the basis of solvolysis with anhydrous HF and 1H- and
      13C-NMR spectral data, including NOE experiments, it was concluded that the
      capsular polysaccharide had the following structure containing novel N-acyl-amino
      sugar and bacillosamine residues: --> 3)-alpha-D-GalpNAc-(1 --> 4)-alpha-L
      GalApNAc(1 --> 3)- alpha-D-QuipNAc4NAc-(1 --> 3)-beta-D-Quip4NAlaAc-(1 -->

PMID- 7585722
TI  - Liquid-crystal properties of octyl 6'-O-alkylmelibiosides.
AB  - 6-O-alpha-D-Galactopyranosyl-D-glucopyranose (melibiose) derivatives with alkyl
      groups at the terminal 1-O and 6'-O positions have been synthesized. They show
      thermotropic and lyotropic liquid-crystal properties. The d-spacings of the
      strong inner X-ray diffraction rings correspond to approximately 0.9 times the
      extended length of the molecule. The molecules are therefore either extended in
      monomolecular layers or U-shaped in bimolecular layers.

PMID- 7585718
TI  - Synthesis and crystal structure of methyl 4-6-dideoxy-4-(3-deoxy-L- glycero
      tetronamido)-2-O-methyl-alpha-D-mannopyranoside, the methyl alpha-glycoside of
      the terminal unit, and presumed antigenic determinant, of the O-specific
      polysaccharide of Vibrio cholerae O:1, serotype Ogawa.
AB  - Methyl 4-azido-4,6-dideoxy-3-O-benzyl-alpha-D-mannopyranoside and its analogous 3
      O-(4-methoxybenzyl) derivative were methylated and the 2-O-methyl derivatives
      formed were converted into methyl 4-amino-4,6-dideoxy-2-O-methyl-alpha-D-
      mannopyranoside [sequence: see text]. Reaction of the latter with 3-deoxy-L
      glycero-tetronolactone gave the methyl glycoside of 4,6-dideoxy-4-(3-deoxy-L
      glycero- tetronamido)-2-methyl-alpha-D-mannopyranose [sequence: see text], the
      monosaccharide that is reported to be the terminal moiety of the O-specific
      polysaccharide of Vibrio cholerae O:1, serotype Ogawa. The unit cell packing of
      the compound, which crystallized as a monohydrate, differs from that of the
      previously described crystalline compound lacking the 2-O-methyl group. The
      unmethylated sugar is the terminal moiety of the O-specific polysaccharide of
      Vibrio cholerae O:1, serotype Inaba. The crystal structure of methyl 4,6-dideoxy
      2-O- methyl-4-trifluoroacetamido-alpha-D-mannopyranoside [sequence: see text] is
      also described.

PMID- 7585723
TI  - Synthesis of 1D-(1,3,5/2,4)-4-acetamido-5-amino-1,2,3-cyclohexanetriol and its
      incorporation into a pseudo-disaccharide.
AB  - The synthesis of the title compound and 1D-(1,3,5/2,4)-4-acetamido-5-amino-3-O
      (beta-D-glucopyranosyluronic acid)- 1,2,3-cyclohexanetriol [sequence: see text]
      is described. Starting from methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside 2L
      (2,4,5/3)-4-acetamido-3-benzoyloxy-2-benzyloxy-5- hydroxycyclohexanone [sequence:
      see text] was prepared via a series of transformations including the
      regioselective ring opening of the benzylidene acetal and the mercury(II)
      catalyzed carbocyclic ring closure reaction of 5-enopyranoside. Stereoselective
      reduction of ketone 11 with NaBH(OAc)3 gave 1D-(1,2,4/3,5)-2-acetamido-3-O
      benzoyl-4-O-benzyl-1,3,4,5- cyclohexanetetrol [sequence: see text] (88%), which
      was then converted into 1D-(1,3,5/2,4)-4-acetamido-5-azido-3-O-benzoyl-2-O-
      benzyl-1-O-pivaloyl-1,2,3-cyclohexanetriol [sequence: see text] through selective
      5-OH protection, 1-O-mesylation, and subsequent azide displacement.
      Saponification and hydrogenation of this gave the title compound. Selective O
      debenzoylation with 1.1 equiv of K2CO3 in MeOH gave 1D-(1,3,5/2,4)-4-acetamido-5
      azido-2-O-benzyl-1-O- pivaloyl-1,2,3-cyclohexanetriol [sequence: see text] (73%).
      Glycosylation of this compound with methyl (2,3,4-tri-O-acetyl-alpha-D
      glucopyranosyl bromide) uronate in Ch2Cl2, using silver triflate as the promoter,
      afforded 1D-(1,3,5/2,4)-4-acetamido-5-azido-2-O-benzyl-3-O-(methyl 2,3,4-tri-O
      acetyl-beta-D-glucopyranosyluronate)-1-O- pivaloyl-1,2,3-cyclohexanetriol
      [sequence: see text] and subsequent hydrogenation of this compound gave the basic
      pseudo-disaccharide.

PMID- 7585724
TI  - Association of serum antibodies against defined epitopes of human papillomavirus
      L1, E2, and E7 antigens and of HPV DNA with incident cervical cancer.
AB  - In order to provide a large-scale evaluation of the association with cervical
      cancer of antibodies against human papillomavirus (HPV) antigens, sera from 233
      patients with primary, untreated cervical cancer and from 157 healthy age- and
      sex-matched blood donors were analyzed for IgG and IgA antibodies against HPV
      derived peptide antigens and against bovine papillomavirus. Several serological
      responses were strongly associated with cervical cancer, notably the IgG response
      against the HPV 16 epitopes L1:13 (Relative risk [RR]: 5.3), E2:9 (RR: 2.9), and
      E7:5 (RR: 4.3), and the IgA response against an HPV 18 E2-derived antigen
      (245:18, RR: 3.1). HPV DNA in corresponding cervical tumors was analyzed by
      Southern blotting (SB) and polymerase chain reaction (PCR) in 47 patients. Sixty
      six percent of the patients carried HPV DNA as determined by SB, 91% of patients
      analyzed by PCR. Neither the antibody responses, nor the presence of HPV DNA were
      significantly associated with the biological properties of the tumors.

PMID- 7585725
TI  - Detection of antibodies to avian leukosis/sarcoma viruses (ALSV) and
      reticuloendotheliosis viruses (REV) in humans by ELISA.
AB  - We used a modified commercial ELISA kit to test for antibodies to avian
      leukosis/sarcoma and reticuloendotheliosis viral antigens in the sera of 45
      poultry workers and their matched controls. We found that 42% of sera from
      poultry workers had anti-avian leukosis Sarcoma viruses (anti-ALSV) and 20% had
      anti-reticuloendotheliosis viruses (anti-REV), antibody titers that were higher
      than the highest titer recorded in control subjects, and hence were regarded as
      positive. To determine the specificity of these reactions, selected sera were
      absorbed with ALSV or REV antigens alone, or with chick embryo fibroblasts (CEF)
      alone, or with both CEF and ALSV/REV, and then retested. In each case, absorption
      resulted in a statistically significant reduction in absorbance, which was
      greatest for the combined CEF and ALSV/REV absorption, thus suggesting that the
      reactions involved viral as well as chicken antigens. However, definitive tests
      such as Western Blot analyses are needed to confirm whether indeed antibodies to
      these viruses were specifically elicited in human sera.

PMID- 7585726
TI  - Cytotoxic and transforming effects of some iron-containing minerals in Syrian
      hamster embryo cells.
AB  - Four physicochemically characterized iron-containing minerals, one fibrous (a
      nemalite [brucite]) and three nonfibrous (a biotite [phyllosilicate], a magnetite
      (Fe3O4), and a goethite [FeOOH alpha]), were studied for cytotoxicity and
      morphological transformation of Syrian hamster embryo (SHE) cells. When colony
      forming efficiency was used as a measure of cytotoxicity, it appeared that the
      nemalite was about 1.7-fold more cytotoxic than the biotite and magnetite.
      However, if the inhibitory effect on the cell growth was considered the nemalite
      appeared to be 8-fold more effective. The analysis of the cell cycle kinetics by
      flow cytometry revealed a time- and dose-dependent delay in the progression of
      cells through the cell cycle, with the accumulation of cells in S and G2-M
      phases, more particularly in the cultures treated with nemalite. While the
      goethite was neither cytotoxic nor transforming, the other three dusts were, in a
      dose-dependent manner, efficient in inducing morphological transformation of SHE
      cells. According to their transforming potency they ranged as follows: nemalite >
      biotite > magnetite. A 18-fold higher treatment concentration of magnetite than
      that of nemalite was necessary to induce the same transformation frequency. The
      iron chelator desferrioxamine abolished the transforming effect of nemalite. The
      results suggest that (i) the cytotoxicity and the transformation are induced by
      some divalent iron-containing minerals and that they are two distinct processes;
      (ii) there is a varying ability among these dusts to induce cell transformation;
      and (iii) the bioavailability of divalent iron leading to formation of reactive
      iron-oxygen species could mediate the transforming potency of a mineral.
      Physicochemical studies correlated to biological effects of many metallic mine
      dusts are the only approach for understanding their mechanisms of action and
      their role in occupational pathology.

PMID- 7585727
TI  - The effect of dietary omega-3 polyunsaturated fatty acids on T-lymphocyte subsets
      of patients with solid tumors.
AB  - The effect of omega-3 polyunsaturated fatty acids (PUFA) on the immune system
      seems to be beneficial. There has been a number of studies concerning the effect
      of dietary omega-3 PUFA on different immune parameters. The aim of our present
      study was to investigate the effect of dietary omega-3 PUFA on T-cell subsets and
      natural killer (NK) cells of patients with solid tumors. We studied 20 patients
      with solid tumors who received 18 g fish oil/day for 40 consecutive days. We
      detected a significant increase in T-helper/T-suppressor cell ratio 40 days into
      omega-3 supplementation, due mainly to a decrease in the number of suppressor T
      cells. We concluded that dietary omega-3 fatty acids may have a beneficial effect
      on the already compromised immune system of patients suffering from solid tumors.

PMID- 7585728
TI  - Chemoprevention of the naturally occurring carcinogen 1-hydroxyanthraquinone
      induced carcinogenesis by the nonsteroidal anti-inflammatory drug indomethacin in
      rats.
AB  - The chemopreventive effect of the nonsteroidal anti-inflammatory drug
      indomethacin (IMC) on 1-hydroxyanthraquinone (1-HA)-induced carcinogenesis was
      investigated in a total of 69 male ACI/N rats. Animals in Group 1 were fed the
      diet containing 1.5% 1-HA for 48 weeks. The rats in Group 2 were given the 1-HA
      diet together with 16 ppm IMC in the drinking water for 48 weeks. Group 3 was
      given IMC alone throughout the study. Group 4 was served as an untreated control.
      At the end of the study, the incidences of large bowel and forestomach tumors in
      Group 2 were significantly smaller than those in Group 1 (large bowel tumors:
      0/14 rats, 0% in Group 2 versus 12/27 rats, 44% in Group 1, p < 0.002;
      forestomach tumors: 2/14 rats, 14% in Group 2 versus 14/27 rats, 52% in Group 1,
      p < 0.01). Also, the incidences of inflammatory changes including ulcerative
      colitis and melanosis coli in colonic mucosa of rats of given 1-HA together with
      IMC were significantly reduced compared with those in rats given 1-HA alone
      (ulcerative colitis: 2/14 rats, 14% in Group 2 versus 20/27 rats, 74% in Group 1,
      p < 0.004). Concurrent administration of IMC with 1-HA caused a significant
      decrease in the bromodeoxyuridine labeling index of the colonic mucosa. These
      results indicate that the nonsteroidal anti-inflammatory drug IMC inhibits 1-HA
      induced carcinogenesis and that this effect in decreasing the cell proliferation.

PMID- 7585729
TI  - IgD myeloma: clinical characteristics and a new staging system based on analysis
      of Japanese patients.
AB  - The aim of this review was to compare the clinical characteristics and prognostic
      factors of Japanese and Western IgD myeloma patients, and also to introduce our
      new staging system, based on the analysis of Japanese patients. We reviewed 165
      Japanese with IgD myeloma reported since the first Japanese case report in 1967
      and compared these patients with Western IgD myeloma patients reported in the
      literature. Parameters evaluated were recorded at diagnosis. The staging systems
      of Durie and Salmon and the British Medical Research Council (BMRC) were also
      applied to our series. Survival curves were calculated according to the method of
      Kaplan & Meier and generalized Wilcoxon test and log-rank test were used to
      assess differences in survival. Multivariate analysis was performed by the Cox
      proportional hazard model. We were able to confirm the similarity of clinical
      features in Japanese patients and those reported in Western countries. We did,
      however, find small differences in the incidence of lymphadenopathy,
      thrombocytopenia, and high serum levels of creatinine, and in the 5-year survival
      rates. Assessment of prognostic factors influencing survival was compared in
      Japanese and Western patients. A multiple regression model in our series showed
      that light chain subtype and leukocyte count had a strong predictive relationship
      for duration of survival. A new risk grouping using these two major factors was
      introduced since neither the common staging system of Durie & Salmon nor those of
      the BMRC predicted survival in these patients; to date, there are still no
      reports from Western countries in this regard.

PMID- 7585731
TI  - Metabolism of dehydroepiandrosterone sulphate by breast cysts: possible role in
      the development of breast cancer.
AB  - Women with palpable breast cysts may have a higher risk of developing breast
      cancer. High concentrations of androgens and oestrogens have been found in breast
      cyst fluid, some of which may be implicated in mammary carcinogenesis. The aim of
      this study was to investigate whether breast cysts were capable of metabolizing
      radiolabeled dehydroepiandrosterone sulphate and, if so, to identify the
      metabolites formed. Breast cysts were found to possess the enzyme systems
      required for converting dehydroepiandrosterone sulphate to
      dehydroepiandrosterone, androstenedione, androstenediol, and testosterone.
      Steroid metabolism by breast cysts may play a role in the development of breast
      cancer.

PMID- 7585730
TI  - Changes in the number of silver-stained nucleolar organizer regions in the
      normal, preneoplastic, and neoplastic endometrium.
AB  - The number of silver-stained nucleolar proteins (AgNORs) were counted in
      preneoplastic and neoplastic endometrial lesions and compared with those of the
      normal endometrium in the menstrual cycle. In glandular cells in the normal
      menstrual cycle, the mean number of AgNORs in the proliferative phase endometrium
      (3.4) was significantly higher than that in the secretory phase endometrium (2.5,
      p < 0.01). The mean number of AgNORs in well-differentiated endometrioid type
      adenocarcinoma (4.2) was significantly greater than that in simple hyperplasia
      (3.0, p < 0.001) and complex hyperplasia without cytological atypia (3.6, p <
      0.05). The average number of AgNORs showed an increased tendency according to the
      neoplastic changes in the endometrium. These findings suggest that the one-step
      colloid method for AgNORs may therefore be a simple and partially useful
      technique for examining the proliferative activity in neoplastic and
      preneoplastic endometrial cells, but no clear distinction in each preneoplastic
      and neoplastic endometrial lesion can be drawn so far from our measurements.

PMID- 7585732
TI  - Growth fractions (Ki-67) in primary breast cancers, with particular reference to
      node-negative tumors.
AB  - We determined the growth fraction in 549 primary breast carcinomas using
      monoclonal antibody Ki-67. With respect to the course of disease, significant
      differences emerged for the whole collective as well as among the node-positive
      tumors. We paid special attention to the node-negative (N0) carcinomas in the
      group, the aim being to differentiate a prognostically unfavorable subgroup in
      this otherwise favorable collective. Owing to the comparative rarity of clinical
      events, our findings for such tumors failed to attain statistical significance;
      however, a strong clinical trend indicating an adverse prognosis for both overall
      and disease-free survival emerged for tumors exhibiting a high growth fraction.
      One-quarter of these patients had received adjuvant treatment. In the group
      exhibiting high levels of Ki-67 reactivity, significantly less favorable findings
      with respect to overall survival were observed among the untreated patients. The
      present results seem to confirm previous indications that antibody Ki-67 is of
      value in assessing the prognosis of N0 breast cancer.

PMID- 7585733
TI  - Cancer metastasis: negative regulation by an invasion-suppressor complex.
AB  - Invasion is the hallmark of tumor malignancy. We situate invasion within
      microecosystems comprising neoplastic cells as well as host cells. Modulation of
      invasion within such systems is ascribed to balances between promoter and
      suppressor pathways. The E-cadherin/alpha-, beta-, gamma-catenin complex has an
      invasion-suppressor function as evidenced by transfections either with sense cDNA
      encoding these molecules or with antisense cDNA inhibiting their expression. Loss
      of heterozygosity at the E-Cadherin (uvo) locus has been reported, but mutations
      in the E-cadherin gene seem to be rare. Downregulation of E-cadherin occurred at
      the level of transcription or of mRNA stability. Ex vivo cultures from invasive
      tumors or metastases produced cells that were homogeneously E-cadherin-positive
      and noninvasive in vitro. These observations have led to the idea that factors in
      the host downmodulate the E-cadherin complex and promote invasion most probably
      in a transient way.

PMID- 7585735
TI  - Solving nomenclature problems in cardiology. II. Updating terminology in clinical
      cardiology.

PMID- 7585734
TI  - Solving nomenclature problems in cardiology. I. Updating terminology in
      electrocardiography.

PMID- 7585736
TI  - Aggressive interventional treatment of acute myocardial infarction. Lessons from
      the animal laboratory applied to the catheterization suite.
AB  - Myocardial necrosis progresses with the duration of coronary occlusion in the
      early stages of acute myocardial infarction. Prompt recanalization of the infarct
      related artery resulting in effective and sustained reperfusion of jeopardized
      myocardium is the goal of modern therapy. Clinical thrombolysis trials have
      demonstrated a significant survival advantage for treated patients, but only a
      modest recovery of global or regional systolic left ventricular function.
      Accelerated regimens of administering currently available thrombolytic agents are
      associated with early coronary patency rates approaching 85%, although effective
      coronary perfusion is restored in only slightly better than one half of patients
      treated. Primary angioplasty without antecedent thrombolytic therapy has resulted
      in high patency rates with superior coronary flow when performed in some
      experienced centers. Treatment of cardiogenic shock requires immediate mechanical
      or surgical intervention to reestablish coronary perfusion often following
      placement of a circulatory assistance device. Future trends toward very early
      initiation of thrombolytic therapy, improvements in adjunctive therapy and
      advances in the noninvasive detection of recanalization should permit selective
      use of aggressive interventional therapy for failed thrombolysis in a minority of
      patients with acute myocardial infarction.

PMID- 7585739
TI  - Oximetry catheters in diagnostic heart catheterization in children.
AB  - The aim of this study was to assess the performance of pediatric-size oximetry
      catheters in diagnostic heart catheterization. Measurements of pressures and
      oxygen saturations were obtained with oximetry catheters as well as with standard
      methods during routine heart catheterizations in 10 infants and children with
      congenital heart defects. Maneuverability of the oximetry catheters was
      comparable to that of standard Swan-Ganz catheters. Pressure tracings were
      damped, but mean pressures were undistorted. Oxygen saturation measurements
      exhibited bias and scatter. It is concluded that no advantage is obtained by the
      use of oximetry catheters in diagnostic heart catheterization in children and
      infants.

PMID- 7585740
TI  - Angiographic follow-up of coronary artery ectasia.
AB  - Of 1,125 patients catheterized over a period of 8 years, 68 (6%) had coronary
      ectasia. Twenty-five of them were catheterized at least twice and constituted the
      study group. The time between the first and last catheterization ranged from 2 to
      8 years (mean +/- SD = 4.2 +/- 1.6). Coronary ectasia was more frequent in males
      (88%). The frequency of involvement was: the right coronary (47%), the left
      circumflex (30%), the left anterior descending (21%) and the left main arteries
      (2%). Proximal segments were most frequently involved (48%). Diffuse involvement
      was found in 29%. Severity of ectasia progressed in 6 segments (14%) and 2 new
      ectatic segments appeared over the follow-up period. During that period, 2
      patients had myocardial infarction, 1 of them due to a total occlusion of an
      ectatic segment. There were no deaths. In conclusion, coronary ectasia has a
      relatively benign course.

PMID- 7585738
TI  - Predictors of the effect of heparin during cardiac catheterization.
AB  - This study was designed to determine if the activated partial thromboplastin time
      (aPTT) present at the end of a diagnostic cardiac catheterization was correlated
      with specific patient or procedure characteristics. No relationship between time
      from heparin bolus and the aPTT was found. Age, weight and body surface area were
      found to influence the aPTT at catheterization completion (p < 0.05). Patient
      sex, height, smoking status, hematocrit, and type and volume of contrast used
      were not correlated with aPTT at the end of catheterization. This suggests
      possible usefulness of the age and weight of patients to guide the dose of
      heparin used at cardiac catheterization.

PMID- 7585737
TI  - Relationship of cigarette smoking to the severity of coronary and thoracic aortic
      atherosclerosis.
AB  - We studied the relationship of cigarette smoking to the severity of coronary and
      thoracic aortic atherosclerosis in 116 men who received coronary angiography and
      transesophageal echocardiography. Severity of coronary atherosclerosis was
      assessed in terms of Gensini's score (GS), and that of thoracic aortic
      atherosclerosis was assessed by the average sclerotic length (ASL) and average
      sclerotic area (ASA). The plasma fibrinogen levels were significantly positively
      correlated with smoking, and fasting blood sugar levels tended to be positively
      associated with smoking. GS was inversely associated with serum levels of high
      density lipoprotein (HDL) cholesterol. ASL and ASA were positively associated
      with age, fasting blood sugar levels and plasma fibrinogen levels, and these
      associations were statistically significant. Analysis of covariance was used to
      examine the net association between cigarette smoking and GS, ASL or ASA
      controlling for age, total cholesterol, HDL cholesterol, fasting blood sugar and
      plasma fibrinogen. We found that GS, ASL, and ASA were all significantly
      increased with increasing number of cigarette years. Additional adjustment for
      other risk factors (triglyceride, uric acid, body mass index, alcohol use and
      hypertension) also showed a strong independent contribution of smoking to GS, ASL
      and ASA. We concluded that the cumulative exposure to cigarette smoking was an
      independent indicator of the severity of coronary atherosclerosis as well as
      thoracic aortic atherosclerosis.

PMID- 7585742
TI  - Cardiovascular function during brain natriuretic peptide infusion in man.
AB  - To investigate the cardiovascular effects of pathophysiological levels of brain
      natriuretic peptide (BNP), 7 healthy subjects were submitted to equilibrium
      radionuclide angiocardiography in baseline conditions and during BNP infusion at
      increasing doses (4, 8, 10 and 12 pmol/kg.min for 20 min each). BNP induced a
      progressive, significant reduction in left ventricular end diastolic volume,
      stroke volume and end systolic volume and an increase in ejection fraction and
      heart rate. Cardiac output, arterial pressure and peripheral vascular resistance
      were unchanged. Activation of the sympathetic nervous system, as indicated by the
      significant increase in plasma norepinephrine levels, probably played a
      contributory role in the maintenance of cardiovascular homeostasis. These results
      indicate that BNP, at pathophysiological plasma concentrations, influences
      cardiovascular homeostasis in man.

PMID- 7585743
TI  - Incidence of structural cardiac disorders in neonates: an evaluation by color
      Doppler echocardiography and the results of a 1-year follow-up.
AB  - Non-biased 502 consecutive neonates were examined by sectorial and color Doppler
      flow imaging at a mean age of 1.0 day (SD 0.4). Patent foramen ovale was present
      in 266 (53%) and transient patent ductus arteriosus in 104 (21%). Cardiac
      disorders were recognized in 19 (3.8%); ventricular septal defect (VSD) in 10;
      atrial septal defect (ASD) in 4; pulmonary stenosis in 2; aortic stenosis,
      endocardial cushion defect and tricuspid regurgitation in 1 each. With a
      spontaneous closure of 8 VSDs and 4 ASDs during the first 12 months, the
      incidences of cardiac malformation were, consequently, 3.2% at 1 month, 1.4% at 6
      months and 1.0% at 12 months.

PMID- 7585741
TI  - Oral ibopamine substitution in patients with intravenous dopamine dependence.
AB  - In a prospective open study we evaluated whether intravenous dopamine infusions
      can be safely switched to enterally administered ibopamine in dopamine-dependent
      patients. Six patients defined as being clinically stable, normovolaemic, but
      dopamine dependent, i.e. with repeated inability to stop intravenous dopamine,
      were included. Ibopamine was administered via a nasogastric or nasoduodenal tube.
      During the initial 48-hour period of ibopamine administration the dopamine
      infusion was gradually decreased and then discontinued. Arterial blood pressure
      was continuously recorded via a 20-gauge cannula in the radial artery. Urine
      output was measured each hour. In all 6 patients it was possible to decrease and
      then discontinue the dopamine infusion whilst maintaining haemodynamic stability
      and an appropriate diuresis. It was then possible to discharge the patients from
      the intensive care unit. Normovolaemic, clinically stable but dopamine-dependent
      patients may be weaned off intravenous dopamine by substitution of enterally
      administered ibopamine, allowing discharge from the intensive care unit.

PMID- 7585746
TI  - Transesophageal echocardiography as an important tool in the diagnosis of
      postinfarction papillary muscle rupture.
AB  - Papillary muscle complicating acute myocardial infarction is an uncommon but
      potentially catastrophic event. We present 3 such cases to illustrate the
      difficulties in early identification of rupture. In each case, transesophageal
      echocardiography was employed providing rapid and unequivocal identification of
      the disorder. Prompt surgical intervention led to survival in 2 patients.

PMID- 7585745
TI  - High early peak creatine kinase after thrombolysis in patients with acute
      anterior infarction predicts poor left ventricular function.
AB  - Successful thrombolysis alters the pattern of creatine kinase (CK) release to the
      plasma after acute myocardial infarction (AMI). Among the important differences
      there are the early peak of the CK activity curve and the higher peak value for a
      given infarct size. To determine whether the magnitude of peak CK following
      thrombolysis still reflects the extent of myocardial damage, we correlated the
      peak CK value with left ventricular ejection fraction (LVEF) in 114 patients with
      first anterior AMI who had early peak CK ( < or = 12 h) after thrombolysis. There
      was a significant (p < 0.001) linear relation between the peak CK value and LVEF
      both at admission and 2 months later. High ( > or = 1,500 IU/1) as compared with
      low early peak CK was associated with significantly lower LVEF (p < 0.001) and a
      higher incidence of poor LVEF (p < 0.05).

PMID- 7585744
TI  - Plasma plasminogen activator inhibitor-1, tissue plasminogen activator and serum
      lipoprotein(a) after reperfusion therapy in acute myocardial infarction:
      comparison between sequential and direct percutaneous transluminal coronary
      angioplasty.
AB  - To determine which reperfusion therapy for acute myocardial infarction (AMI) is
      advantageous to avoid subsequent thrombotic coronary occlusion, 8 patients with
      AMI were studied. Four of them (group S) underwent sequential PTCA following
      unsuccessful intracoronary thrombolysis and the others (group D) direct PTCA.
      Serial changes in plasma plasminogen activator inhibitor-1 (PAI-1), plasma tissue
      plasminogen activator (t-PA) antigen and serum lipoprotein(a) levels were
      compared between the two groups. In group S, plasma PAI-1 levels showed no
      significant serial change after PTCA. However, in group D, plasma PAI-1 levels
      increased significantly 4-24 h after PTCA. We suggest that more attention should
      be focused on the prevention of thrombotic coronary closure as well as mechanical
      abrupt occlusion after direct PTCA.

PMID- 7585747
TI  - Significance of an atrial septal aneurysm in the presence of an ostium secundum
      atrial septal defect. A transesophageal echocardiographic study.
AB  - The aim of this study was to elucidate the mechanism by which an atrial septal
      aneurysm is formed in the presence of an atrial septal defect by characterizing
      the distinguishing echocardiographic features of atrial septal defects between
      patients with and without an atrial septal aneurysm. The transesophageal
      echocardiograms of 30 consecutive patients who underwent surgical closure of a
      secundum atrial septal defect were compared with those of 8 normal controls. In
      patients with secundum atrial septal defect, the maximal diameter (mean +/- SD)
      of the fossa ovalis was 21.73 +/- 3.43 compared to 11.43 +/- 1.00 mm in the
      control group (p < 0.01). In the 7 (23%) patients with atrial septal aneurysm,
      the mean maximal diameter of the fossa ovalis was 25.28 +/- 3.03 compared to
      20.65 +/- 2.78 mm in those without an atrial septal aneurysm (p < 0.01). The
      atrial septal defect was smaller in patients with than in those without an atrial
      septal aneurysm. In 4 patients with atrial septal aneurysm who had a history of a
      cerebrovascular event, the interatrial communication was only detected by
      contrast echocardiography. In conclusion, in patients with atrial septal
      aneurysm, atrial septal defects tend to be smaller but the incidence of
      cerebrovascular events is greater.

PMID- 7585749
TI  - Interrelationships between lipoprotein(a) and other cardiovascular risk factors.
AB  - Lipoprotein(a) [Lp(a)] had been shown to be a strong independent risk factor for
      ischaemic heart disease. Our aim was to investigate the relationships between
      Lp(a) and other cardiovascular risk factors. 423 male miners (age 40 +/- 8 years)
      were analysed according to the following variables: age, arterial blood pressure,
      alcohol and cigarette consumption, total cholesterol and Lp(a). Analysis of the
      data was performed using the Kruskal-Wallis and Spearman tests. Analysis of
      variance showed statistical differences in Lp(a) levels with cigarette
      consumption (p < 0.02) and age (p < 0.001). No differences with corrected total
      cholesterol, blood pressure and alcohol consumption were found. Lp(a) and total
      cholesterol were correlated (p < 0.0001), but after correction for the estimated
      contribution of Lp(a) cholesterol this significant correlation disappeared. We
      conclude that male smokers have significantly lower Lp(a) values than non-smokers
      and those who quit. Our findings suggest that cigarette consumption is a probable
      environmental factor that might influence Lp(a) levels.

PMID- 7585748
TI  - Long-term prognostic importance of exercise echocardiography after an episode of
      unstable angina.
AB  - The aim of this study was to determine whether exercise echocardiography gives
      long-term prognostic information in patients with unstable angina. Treadmill
      exercise echocardiography was performed before discharge in 33 consecutive
      patients (23 men, 10 women) with unstable angina. A wall motion score index
      (WMSI) was calculated from visual interpretation of 9 left-ventricular segments,
      registered with two-dimensional echocardiography. Within an 8-year follow-up
      period, there were 10 medical events (2 cardiac deaths and 8 myocardial
      infarctions). New or worsening wall motion abnormalities and a low WMSI
      immediately after the exercise test were associated with subsequent myocardial
      infarction or cardiac death during follow-up (p < 0.05). Only 1 of the patients
      with a WMSI above the median suffered a myocardial infarction, which was not
      fatal. In contrast, 9 (56%) of the 16 patients with a WMSI below the median
      suffered myocardial infarction or cardiac death during follow-up. These findings
      in patients with unstable angina suggest that exercise echocardiography is a
      sensitive method for detecting those with increased risk of myocardial infarction
      or cardiac death. These high-risk patients might benefit from a more aggressive
      therapeutic approach.

PMID- 7585750
TI  - Apical segmental dysfunction in hypertrophic cardiomyopathy: progression into end
      stage heart failure with sudden cardiac death.
AB  - Apical segmental dysfunction is an unusual finding in hypertrophic cardiomyopathy
      (HCM). It is characterized by a poor clinical course and a high incidence of
      malignant ventricular tachyarrhythmias. Long-term prognosis of patients with HCM
      and apical segmental dysfunction is still unclear. We report 2 cases of apical
      segmental dysfunction in HCM in whom progressive apical dilatation and congestive
      heart failure developed. Both patients died suddenly, and intractable ventricular
      tachyarrhythmias were documented in 1 case during resuscitation. This report
      provides further evidence that apical segmental dysfunction might predict a
      subgroup of patients with HCM who are likely to develop end-stage heart failure
      and are at high risk of sudden cardiac death.

PMID- 7585752
TI  - Disappearance of the Dressler syndrome.

PMID- 7585751
TI  - Cerebral embolism from the thrombus in the atrioventricular septal aneurysm.
AB  - Atriventricular septal aneurysm is a rare finding. Thrombus within the
      atrioventricular septal aneurysm has never been reported. Here, we report a girl
      with sudden-onset hemiparesis. Magnetic resonance imaging of the patient's head
      revealed a lesion at the right basal ganglion. Cerebral infarction was impressed.
      A series of examinations was performed to find the source of the cerebral
      embolism. Transthoracic echocardiography further showed a thrombus in the
      aneurysm. A subsequent operation revealed a fresh thrombus in the aneurysm. The
      presence of an anatomic substrate such as this might justify anticoagulation
      treatment or even surgical intervention before thromboembolism occurs.

PMID- 7585753
TI  - Short-term effects of captopril on exercise tolerance in patients with chronic
      stable angina pectoris and normal left ventricular function.
AB  - A double-blind, placebo-controlled, crossover study was carried out to evaluate
      the short-term effects of captopril on exercise tolerance in 18 normotensive
      patients with chronic stable angina pectoris and normal left ventricular
      function. Captopril 25 mg (or placebo) was given twice, i.e. in the evening (10
      p.m.) and the following morning (8 a.m.), prior to a maximal symptom-limited
      bicycle exercise test (11 a.m.). Captopril reduced the systolic and diastolic
      blood pressures at rest (p < 0.01) without causing any reflex tachycardia. The
      time to onset of S-T depression was prolonged (p < 0.05), and the maximal S-T
      depression was reduced (p < 0.02). No differences were found between captopril
      and placebo in total exercise duration or time to onset of angina. The effects of
      captopril on exercise-induced ischemia were demonstrated most clearly in patients
      who responded with a greater than 10 mm Hg fall in the resting systolic blood
      pressure. In conclusion, this study suggests that captopril has anti-ischemic
      properties, which may be of importance in the treatment of patients with chronic
      stable angina and normal left ventricular function. These beneficial effects
      probably relate to a reduction in afterload and myocardial wall stress and
      therefore a reduction in myocardial oxygen demand.

PMID- 7585755
TI  - ELAT study (embolism in left atrial thrombi): baseline clinical and
      echocardiographic data.
AB  - By transesophageal echocardiography, the prevalence of left atrial/appendage
      thrombi and spontaneous echo contrast and the size of the left atrial appendage
      and their association with clinical and echocardiographic characteristics were
      evaluated in 409 nonrheumatic atrial fibrillation outpatients (62 +/- 12 years)
      without recent (< 1 year) embolism. Left atrial/appendage thrombi (2.5%) were
      associated with diabetes (p < 0.05), heart failure (p < 0.05) and low fractional
      shortening (p < 0.001); spontaneous echo contrast (12%) with advanced age (p <
      0.01), constant atrial fibrillation (p < 0.01), hypertension (p < 0.01), heart
      failure (p < 0.05), valvular abnormalities (p < 0.01) and large left atrial
      diameter (p < 0.01), and large left atrial appendages with constant atrial
      fibrillation (p < 0.05), diabetes (p < 0.05) and valvular abnormalities (p <
      0.05).

PMID- 7585754
TI  - Normal post-race antimyosin myocardial scintigraphy in asymptomatic marathon
      runners with elevated serum creatine kinase MB isoenzyme and troponin T levels.
      Evidence against silent myocardial cell necrosis.
AB  - Recent epidemiologic studies confirm that heavy physical exertion can trigger
      myocardial infarction. Diagnosis of acute myocardial injury in marathon runners
      is complicated by elevations of serum creatine kinase MB isoenzyme activity in
      asymptomatic finishers with normal post-race infarct-avid myocardial
      scintigraphy. Such isoenzyme elevations can arise from exertional rhabdomyolysis
      of skeletal muscle biochemically altered by training, from silent injury to the
      myocardium or from a combined tissue source. To assess silent myocardial cell
      necrosis in marathon runners, we performed quantitative anti-myosin myocardial
      scintigraphy after competition with serum immunoassays for creatine kinase MB
      isoenzyme and troponin T. Therefore, 8 male marathon runners with a mean age of
      52 years underwent quantitative antimyosin myocardial scintigraphy immediately
      following the 1988 and 1993 Boston Marathons. Serum immunoassays for creatine
      kinase MB isoenzyme by a chemiluminescent method (CLIA) and troponin T by an
      enzyme-linked immunosorbent assay were performed in 4 runners after the 1993
      race. Quantitative antimyosin myocardial scintigraphy was normal in all runners
      including 3 who participated after both races 5 years apart. Post-race serum
      creatine kinase MB isoenzyme and/or troponin T levels were in a range otherwise
      diagnostic of acute myocardial infarction in 3 of 4 subjects. Normal quantitative
      antimyosin myocardial imaging in asymptomatic marathon runners excludes silent
      myocardial cell necrosis as the source of elevated serum protein markers. Such
      imaging may be the optimal diagnostic modality for detection of myocardial cell
      necrosis in symptomatic athletes when results of conventional testing are
      inconclusive.

PMID- 7585756
TI  - Isolated right atrial tamponade after open heart surgery: role of
      echocardiography in diagnosis and management.
AB  - Ten patients with isolated right atrial tamponade complicating open heart surgery
      were identified over a 3.5-year period at three institutions. Clinical
      manifestations varied but were typically those of decreased perfusion with
      elevated central venous pressure. Hemodynamically these patients had systemic
      hypotension and tachycardia with elevated central venous pressure but without
      elevation of pulmonary artery or pulmonary artery wedge pressures. The correct
      diagnosis in each case was established by echocardiography; 7 via the
      transthoracic and 3 via the transesophageal approach. The typical
      echocardiographic feature was an extrinsic extracardiac mass compressing the
      atrium. Doppler findings included high flow velocities through the right atria,
      and color flow demonstrated narrow color jets through compressed, slit-like right
      atria. Surgical exploration confirmed these findings in each case. We conclude
      that the combination of clinical awareness and appropriate hemodynamic evaluation
      can alert the physician to the possibility of isolated right atrial hematoma
      causing decreased perfusion and/or shock following open heart surgery.
      Echocardiography using either the transthoracic or transesophageal approach can
      establish the diagnosis and lead to timely surgical intervention.

PMID- 7585757
TI  - Left ventricular impairment in arrhythmogenic right ventricular dysplasia: what
      we can learn from angiography.
AB  - Left ventricular impairment of arrhythmogenic right ventricular dysplasia is a
      common feature. Angiographic left ventricular contraction abnormalities can be
      found in more than 20% of patients with arrhythmogenic right ventricular
      dysplasia. Left ventricular impairment appears at all functional and
      morphological stages of the disease, even in cases with only slight or moderate
      right ventricular dysfunction. An event of aborted sudden cardiac death with
      documented ventricular fibrillation can be found in 56% of patients with left
      ventricular impairment. Left ventricular abnormalities seem to be an independent
      risk factor of sudden cardiac death; this is particularly true in patients with
      cardiac arrest as the first manifestation of the disease.

PMID- 7585758
TI  - Successful treatment of hyponatremia with angiotensin-converting enzyme
      inhibitors in patients with congestive heart failure.
AB  - Hyponatremia commonly complicates the clinical course of patients with congestive
      heart failure (CHF) and seems to be an ominous prognostic factor. Angiotensin
      converting enzyme (ACE) inhibitors improve the symptomatology of CHF patients.
      Moreover, it has been reported that these drugs can raise serum sodium in
      hyponatremic patients. The aim of this prospective work was to study the
      mechanisms involved in the correction of hyponatremia in 6 patients aged 52-69
      years with CHF and hyponatremia (serum sodium 125-128 mmol/l) who were receiving
      digitalis and furosemide. In these patients, captopril was introduced in
      progressively increasing doses. The drug induced significant clinical
      improvement. Additionally, a statistically significant increase in serum sodium
      was observed which was correlated to a rise in the diluting ability of the kidney
      (increase in CeH2O). A slight increase in creatinine clearance was also found,
      which could have contributed to the improvement in hyponatremia. Therefore, we
      conclude that ACE inhibitors can improve hyponatremia in CHF patients by
      increasing the urinary diluting ability.

PMID- 7585759
TI  - Antihypertensive efficacy of optimally titrated doses of once-daily sustained
      release diltiazem: a placebo-controlled trial. DILPLACOMP Study Group.
AB  - This study assessed once-daily sustained-release (o.d. SR) diltiazem in essential
      hypertension; 158 patients with supine diastolic blood pressures (BP) of 95-115
      mm Hg were randomized to 200 mg diltiazem or placebo, then optimally titrated, at
      2-week intervals, to 200, 300 or 400 mg to achieve supine diastolic BP < 90 mm Hg
      or a > or = 10 mm Hg fall from baseline. BP was measured at trough level, 24 h
      after dosing. After 2 weeks at the dose of 200 mg, supine diastolic BP was
      significantly reduced (from 101 to 92 mm Hg) compared with placebo (from 101 to
      98 mm Hg; p < 0.001), and yielded 57% of responders with diltiazem against 22%
      with placebo (p < 0.001). Titration allowed supine diastolic BP normalization
      with diltiazem (88 mm Hg) compared with placebo (93 mm Hg; p < 0.001) and yielded
      78% of responders with diltiazem against 37% with placebo (p < 0.01). The safety
      profile was similar to placebo. 200 and 300 mg o.d. SR diltiazem formulations
      enable safe and close regimen adjustments in mild-to-moderate essential
      hypertension.

PMID- 7585760
TI  - Seven-year experience of noninvasive preoperative diagnostics in children with
      congenital heart defects: comprehensive analysis of 2,788 consecutive patients.
AB  - The spectrum of patients operated on without preoperative catheterization and
      angiography, the accuracy of echocardiographic diagnosis and its impact on the
      results of surgical treatment were prospectively assessed in 2,788 children
      consecutively operated for congenital heart defects (CHD) between 1986 and 1992.
      The overall percentage of surgery based solely on noninvasive preoperative
      examination increased from 63% in 1986 to 81% in 1990 and decreased to 72% in
      1992. There were no differences in the preoperative diagnostic approach between
      groups of newborn, infants and children. A high percentage of patients with
      patent ductus arteriosus (96.5%), atrial septal defect (94%), incomplete
      atrioventricular septal defect (88.6%), ventricular septal defect (86.3%),
      coarctation of the aorta (80.2%) and total anomalous pulmonary venous connection
      (79.3%) was referred for surgery without prior invasive examination, while a
      lower percentage was found in univentricular heart (48.4%), pulmonary atresia
      (34.6%) and double outlet right ventricle (27.7%). More patients with pulmonary
      and tricuspid atresia were catheterized before complete repair compared to those
      who underwent palliative surgery (p < 0.01 and p < 0.0001, respectively). The
      echocardiographic diagnosis was correct in 96% of patients. Two patients of those
      with incomplete preoperative diagnosis died early postoperatively, both with
      missed apical ventricular septal defect. One with tetralogy of Fallot died after
      reoperation, the other with persistent truncus arteriosus due to sepsis. When the
      echocardiographic findings are in full agreement with the clinical status,
      physical examination, ECG and chest X-ray, we recommend cardiac surgery without
      prior catheterization in many patients with CHD.

PMID- 7585761
TI  - Smoking habits in consecutive patients with acute myocardial infarction:
      prognosis in relation to other risk indicators and to whether or not they quit
      smoking.
AB  - In all patients hospitalized in one single hospital due to acute myocardial
      infarction (AMI) during a period of 21 months, we describe the prognosis in
      relation to smoking habits and other risk indicators with death. Of 862 AMI
      patients, 37% reported smoking at the onset of AMI. Of the patients who smoked at
      the onset of AMI and who survived the first year, 53% reported having quit
      smoking. Patients who had quit smoking reported fewer symptoms of chest pain (p <
      0.01), headache (p < 0.01) and dizziness (p < 0.001) as compared with patients
      who continued to smoke after one year. Of the patients who had quit smoking, the
      mortality during the subsequent 4 years was 17% as compared with 31% for patients
      who continued to smoke (p < 0.05). However, patients who quit smoking less
      frequently had a previous history of myocardial infarction and congestive heart
      failure. When correcting for such dissimilarities, quitting smoking did not
      remain significantly associated with prognosis.

PMID- 7585762
TI  - Two-dimensional echocardiographic evaluation of left ventricular ejection
      fraction by the ellipsoid single-plane algorithm: a reliable method for assessing
      low or very low ejection fraction values?
AB  - The reliability of two-dimensional (2D) echocardiographic estimation of left
      ventricular ejection fraction (EF) is commonly recognized, but no satisfactory
      data are available about the accuracy of low or very low EF values determined by
      2D echocardiography (ECHO-EF). The purpose of our study was to assess the
      reliability of low ECHO-EF values obtained using a simple time-economical
      algorithm such as the ellipsoid single-plane area-length method. Radionuclide
      angiography (RAD-EF) was taken as the standard of comparison. We studied 59
      consecutive patients (31 women and 28 men) referred to our echocardiographic
      laboratory. Both 2D echocardiography and radionuclide angiography were blindly
      performed within 48 h of one another. EF was calculated by the two methods and
      then compared. Data were globally analyzed. Furthermore, data were divided and
      analyzed according to the ECHO-EF cut-off point of 50%. An ECHO-EF value of 50%
      was chosen to conventionally distinguish between low ECHO-EF values and normal
      high ones. Data were plotted, and the line of equality and the regression lines
      were drawn. Regression line slopes, correlation coefficients, means and standard
      deviations were calculated. The agreement was analyzed by calculating the mean
      difference (RAD-EF-ECHO-EF) and the standard deviation of the differences. ECHO
      EF was linearly related to RAD-EF even when data were split. In particular, as
      regards ECHO-EF < or = 50%, the regression line practically overlapped the line
      of equality, and the two methods showed both a strong correlation and a good
      degree of agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585763
TI  - Doppler echocardiographic determination of geometric orifice areas in mechanical
      aortic valve prostheses.
AB  - In 63 St. Jude bileaflet and 34 Bjoerk-Shiley tilting disk aortic valve
      prostheses, Doppler continuity areas were compared to their corresponding
      geometric areas defined by the opening angle of the occluders. Continuity areas
      correlated significantly with geometric areas in Bjoerk-Shiley (p = 0.68) and St.
      Jude prostheses (p = 0.86). Differences between continuity and geometric areas
      were greater in St. Jude than in Bjoerk-Shiley valves (0.87 +/- 0.45 cm2 vs. 0.06
      +/- 0.47 cm2, p < 0.0001). Exclusion of patients with atrial fibrillation, with a
      postoperative interval of less than 1 year or valve sizes of 19 and 21 mm did not
      change the results. Thus, underestimation of geometric areas is present in the
      St. Jude bileaflet aortic valves, while geometric and continuity areas are not
      significantly different in Bjoerk-Shiley prostheses. These results are
      attributable to the effect of valve-type-dependent velocity profiles.

PMID- 7585764
TI  - Comparison of digital dipyridamole stress echocardiography and upright bicycle
      stress echocardiography for identification of coronary artery stenosis.
AB  - This study compared the diagnostic accuracy of dipyridamole (0.84 mg i.v./10 min)
      and bicycle stress echocardiography in 37 patients with inconclusive standard
      bicycle electrocardiography (ECG) tests; all underwent coronary angiography.
      Sensitivity for detection of coronary stenosis with dipyridamole echocardiography
      was 68% (21 of 31 patients), and for 1-, 2- and 3-vessel disease 56, 69 and 83%,
      respectively. Overall bicycle echocardiography sensitivity was 84%, and 78, 88
      and 83% for patients with 1-, 2- and 3-vessel disease, respectively. Dipyridamole
      echocardiography was negative in all 6 patients with negative coronary
      angiography (specificity 100%), bicycle echocardiography was positive in 2
      (specificity 67%). We conclude that dipyridamole echocardiography tends to be
      less sensitive in patients with mild disease, but is more specific than bicycle
      echocardiography.

PMID- 7585765
TI  - The presentation of a double aortic arch in adulthood in association with
      congestive heart failure attributed to a previously silent aortic regurgitation.
AB  - This paper describes an adult case of a double aortic arch (DAA; Edwards type
      IA). The patient had been asymptomatic for DAA but presented difficulty in
      swallowing in association with congestive heart failure, which she experienced as
      the result of attending to her sick husband while she apparently suffered from a
      silent aortic regurgitation. The symptoms disappeared and the patient recovered
      from heart failure following medical treatment. The patient soon discontinued the
      outpatient treatment and, after 2 years, the identical symptoms recurred under
      similar circumstances. In this paper we demonstrate that an asymptomatic case of
      DAA has the potential to clinically manifest itself.

PMID- 7585767
TI  - Rapid diagnosis of acute myocardial infarction.
AB  - At present the ideal method for the very early and very rapid diagnosis of acute
      infarction is still elusive, making it difficult to implement strategies in large
      numbers of patients. With further research and conjoint biochemical and imaging
      approaches, however, it is likely that the early diagnosis of infarction and
      detection of ischemia will be possible.

PMID- 7585766
TI  - Ectopic thyroid tissue in the ventricular outflow tract: embryologic
      implications.
AB  - The case of a 66-year-old female patient with a tumor located in the right
      ventricular outflow tract is reported. Histologic examination of an
      intraoperative biopsy revealed that the tumor was an intracardiac ectopic
      thyroid. We performed conservative surgery with partial resection of the mass.
      After 5 years, the patient is asymptomatic and leading a normal life. The authors
      examine the relation between the embryologic development of the primitive heart
      and the thyroid primordium and suggest the hypothesis of ectopic thyroid location
      in the right- or left-ventricular outflow tract.

PMID- 7585770
TI  - Direct angioplasty in acute myocardial infarction. State of the art and current
      controversies.
AB  - Although direct angioplasty may have been undervalued in the past, its utility in
      the treatment of acute coronary occlusion is now firmly established, and it
      unquestionably will remain an integral component of myocardial reperfusion
      therapy. As refinements in angioplasty equipment, cardiovascular support
      techniques, and adjunctive therapy occur, the challenge facing cardiologists in
      the 1990s will be to define the most effective role for direct angioplasty in the
      treatment of acute myocardial infarction.

PMID- 7585769
TI  - Streamlining the triage system for acute myocardial infarction.
AB  - The full benefits of thrombolytic therapy can be realized if and only if
      treatment is delivered as quickly as possible. Streamlining the triage system
      will not only increase the numbers of patients treated with thrombolytic therapy,
      it will ultimately reduce mortality and morbidity rates from acute myocardial
      infarction by limiting loss of heart muscle. Reducing the time to treatment,
      however, is a daunting task given that both patient and hospital delays
      contribute to the underutilization or inefficient use of thrombolytic therapy. In
      particular, patient delays can be difficult to attenuate, given that human
      behavior is complex and that designing interventions to change behavior is not
      only challenging but expensive. Results from the MITI registry show that the
      emergency medical system is the linchpin of an efficient triage system in that it
      is associated with reduced patient delays as well as reduced treatment delays.
      Clearly, patients with chest pain need to be aware of the need to take prompt
      action by calling 911. On the other hand, decisions to use these systems to
      acquire electrocardiograms or deliver thrombolytic treatment will be faced by
      increasing numbers of administrators and policy makers in the years to come.
      Without adequate community support to maintain and improve these systems, the
      full benefits of thrombolytic therapy cannot be attained.

PMID- 7585771
TI  - Risk-benefit of thrombolysis.
AB  - In larger trials the relative reduction in mortality rates brought about by
      thrombolytic therapy is similar among various subgroups. Accordingly, the
      absolute mortality reduction by thrombolytic therapy is largest in patients with
      the greatest expected mortality in the placebo groups. Similarly, the additional
      benefit by accelerated tissue plasminogen activator (TPA) is proportional to the
      expected mortality without thrombolytic therapy. Using logistic regression
      analysis a table has been developed predicting the survival benefit from
      thrombolytic therapy in groups of patients with different baseline
      characteristics. A table also has been developed to predict the risk of
      intracranial hemorrhage from thrombolytic therapy. Using these two tables, an
      individual risk/benefit assessment can be made. In most patients the benefits of
      thrombolytic therapy far exceed the risk of intracranial hemorrhage. Similarly,
      the advantage of more intensive therapy (accelerated TPA) exceeds the slightly
      increased bleeding risk. The model presented can help to allocate different modes
      of reperfusion therapy to individual patients, accounting for limited resources.

PMID- 7585768
TI  - Arterial thrombosis for the clinician. Pathobiology and emerging concepts.
AB  - The prevention and treatment of coronary atherosclerosis and thrombosis are
      linked closely by common pathobiologic features. Patient care will undoubtedly
      benefit from an increased knowledge of disease mechanisms and clinical
      expression.

PMID- 7585774
TI  - Angiotensin-converting enzyme inhibitors post-myocardial infarction.
AB  - Results from SOLVD, SAVE, AIRE, GISSI-III, ISIS-IV, and the Chinese Captopril
      Trial suggest that therapy with ACE inhibitors, at least with enalapril,
      captopril, ramipril, and lisinopril, induce significant reduction in morbidity
      and mortality rates in patients with ischemic heart disease, myocardial
      infarction, and a wide range of ventricular function and myocardial infarction.
      SOLVD and SAVE results, in particular, demonstrate improved survival and reduced
      major ischemic events in patients with depressed systolic ventricular function.
      SOLVD points out that institution of ACE inhibitor therapy need not be done
      immediately post-myocardial infarction to accrue benefit. GISSI-III and ISIS-IV,
      on the other hand, suggest that use of ACE inhibitor drugs early post-myocardial
      infarction produces significant, albeit small, benefits when drugs are begun
      early post-event in conjunction with other routinely used therapeutic strategies.
      The prospective, well-designed, and well-controlled nature of these clinical
      trials, the consistency of their findings, and the high level of morbidity and
      mortality in placebo groups establish the importance of preventing ischemic
      events with the prescribed ACE inhibitors. Particularly important is the fact
      that none of these clinical trials were designed to determine optimal dose or
      frequency of administration of the ACE inhibitors chosen. Targeting dose
      principles were utilized and clinicians wishing to generate similar results in
      their own patient population should choose one of the ACE inhibitors studied and
      administer it in the manner described in hopes of achieving outcomes similar to
      those detailed in the summarized clinical trials. Finally, recommendations
      regarding post-myocardial infarction therapy with ACE inhibitors can be
      summarized. Patients having acute or remote infarction should have an assessment
      of ventricular function. All patients with depressed systolic function, whether
      they are or are not symptomatic, should receive a trial of an appropriate ACE
      inhibitor. Patients suffering an acute myocardial infarction should have an
      assessment of ventricular function early and, if the ejection fraction is low
      (probably < 50%), an appropriately chosen ACE inhibitor should be begun after 24
      hours have elapsed. ACE inhibitor therapy should be begun in combination with
      other proven effective post-myocardial infarction treatment strategies. In
      patients with normal systolic function, advantages of ACE inhibitor therapy are
      less clear, but patients with large anterior wall myocardial infarction will
      likely benefit, even without objective evidence of left ventricular systolic
      dysfunction. Concomitant utilization of thrombolytic agents, aspirin, and beta
      blockers should not interdict use of ACE inhibitor therapy.

PMID- 7585772
TI  - Selecting a thrombolytic agent.
AB  - Streptokinase remains the most widely used agent worldwide, largely because it is
      the cheapest. Because of cost considerations when the incremental cost of the use
      of accelerated TPA exceeds $35,000 (US) per life year added, and because an
      iatrogenically induced stroke in a patient who is otherwise likely to have a good
      outcome is unacceptable, streptokinase may be used in patients with small to
      moderate-sized infarctions and those aged less than 60 years. Streptokinase is
      the agent of choice in patients who have an increased risk of stroke and may be
      used in patients presenting after 6 hours. Streptokinase also may have a role in
      patients with cardiogenic shock. Administration of accelerated TPA is the
      treatment of choice in patients at high risk such as those with large anterior
      infarctions, the elderly, and patients with bypass grafts, and it is an
      alternative to urokinase when streptokinase has been administered previously. The
      most important approach is to treat as many patients as early as possible with
      thrombolytic therapy regardless of which agent is used. Thrombolytic therapy
      still is widely underused. More lives will be saved, regardless of which
      thrombolytic drug is used, by encouraging patients to present early, improving on
      the "door-to-needle" time, and treating more patients with a therapy that can
      save thousands of lives worldwide.

PMID- 7585773
TI  - Prediction of myocardium at risk. Clinical significance during acute infarction
      and in evaluating subsequent prognosis.
AB  - Noninvasive cardiac imaging is currently used to assess myocardial salvage
      following reperfusion therapy for acute myocardial infarction and to stratify
      patients by risk for the development of subsequent cardiac events. The latter is
      most important when deciding who might benefit from coronary angiography and
      revascularization. This article summarizes the roles of radionuclide angiography,
      two-dimensional echocardiography, and myocardial perfusion imaging in the
      clinical assessment and management of patients with acute myocardial infarction.

PMID- 7585775
TI  - Cardiogenic shock.
AB  - Despite advancements in the pharmacologic treatment of acute myocardial
      infarction and the introduction of mechanical hemodynamic support, in-hospital
      mortality rates for cardiogenic shock have remained between 70% and 80%. In
      addition, the proven beneficial effects of thrombolytic therapy in reducing
      mortality in acute myocardial infarction have not been paralleled by similar
      results in cardiogenic shock. Emergency revascularization appears to be the only
      intervention that may modify the prognosis of cardiogenic shock. Because the
      absence of controlled data, however, final conclusions cannot yet be drawn. Two
      ongoing randomized clinical trials will try to answer the unsolved issues. In the
      multicenter international SHOCK trial (Should We Revascularize Occluded
      Coronaries for Cardiogenic Shock), patients are being randomized to PTCA or
      conservative treatment, with mortality as the primary end point. A similar end
      point will be evaluated in the Swiss Multicenter Study of Angioplasty for Shock
      following Myocardial Infarction (SMASH) trial. It is hoped that these two
      randomized trials will be able to prove the value of PTCA in cardiogenic shock
      and identify the subset of patients most likely to benefit from such treatment.

PMID- 7585776
TI  - Role of angiography.
AB  - The role of coronary angiography in acute myocardial infarction is multifaceted.
      In the acute situation--for example, for primary angioplasty, suspected
      thrombolytic failure, or reocclusion--the goal of the angiographer should be
      therapeutic: to provide hemodynamic support, relieve ischemia, and interrupt the
      infarction process. In the nonacute or elective setting after infarction, the
      angiographer's goal should be to obtain diagnostic information only and not to
      approach the catheterization as a definitive therapeutic maneuver. This
      "uncoupling" of diagnostic angiography and revascularization is appropriate in
      light of the numerous trials discussed above. Either an invasive or a noninvasive
      approach to patient management can be justified with currently available data.
      The physician should not feel compelled to proceed with either approach
      necessarily. The patient's comfort level and the physician's comfort level with
      both approaches should be discussed by all concerned, when appropriate for the
      time constraints that exist with acute infarctions. Very likely, in the near
      future the two approaches, invasive and conservative, will undergo further
      analysis and modification as new agents and therapies become available.

PMID- 7585777
TI  - Thrombin inhibitors in acute myocardial infarction.
AB  - Thrombin inhibitors play an important role as part of current (and potential
      future) thrombolytic-antithrombotic regimens for acute myocardial infarction.
      Heparin has been shown to improve infarct-related artery patency following TPA
      and is an integral adjunct to front-loaded TPA and aspirin, the regimen that has
      been demonstrated to be superior to standard thrombolytic regimens. The initial
      experience with direct thrombin inhibitors as an adjunct to thrombolytic therapy
      has shown promising results. They provide a predictable, dose-dependent increase
      in aPTT with a more stable level of anticoagulation than does heparin. Indices of
      infarct-related artery patency have been improved by direct thrombin inhibitors,
      and reocclusion appears to be reduced. In parallel with this improvement in
      coronary reperfusion, there are promising trends toward a lower incidence of
      clinical events as compared with heparin. Thus, it is hoped that these favorable
      initial results can be confirmed in the larger phase III trials and that the
      direct thrombin inhibitors will further improve the outcome of patients with
      acute myocardial infarction.

PMID- 7585779
TI  - Cardiac surgical procedures following myocardial infarction.
AB  - Advances in myocardial preservation have made possible operative intervention
      early post-myocardial infarction or in the face of an evolving myocardial
      infarction. Results are dictated by preoperative factors primarily related to the
      ravages of low flow state. Resuscitation of the myocardium is possible under the
      vast majority of circumstances.

PMID- 7585778
TI  - Platelets and platelet inhibitors in acute myocardial infarction.
AB  - Platelets and platelet-rich thrombi play a pivotal role in the pathogenesis of
      acute myocardial infarction. A ruptured atherosclerotic plaque evokes a
      hemostatic response that is mediated by platelets, its membrane receptors,
      adhesive ligands, the presence or generation of platelet agonists, and the
      activation of the coagulation cascade with fibrin generation. The interaction of
      platelets with the coagulation and the fibrinolytic systems is complex; new and
      exciting developments, however, in the ability to pharmacologically control
      platelet responses during thrombolysis in acute myocardial infarction will
      enhance our understanding of these interactions and will eventually translate
      into clinical benefit.

PMID- 7585780
TI  - How should clinicians interpret clinical trials?
AB  - Given the rapid evolution of cardiovascular medicine, clinicians must sift
      through an enormous array of information about new therapies in order to
      determine how best to treat patients with ischemic heart disease. They should
      first consider the evidence from randomized clinical trials, because these trials
      eliminate bias and permit broad statistical analyses. If randomized clinical
      trial data are not available, next in order of the strength of their evidence are
      observational studies, historically controlled studies, case series, and case
      reports. Clinicians must additionally ascertain that an investigation has the
      elements of good design, including a clear question, adequate sample size,
      appropriate inclusion and exclusion criteria, evidence that the right amount of
      data was collected carefully, and allowances in the analyses for patients taking
      multiple therapies and randomized into several clinical trials.

PMID- 7585782
TI  - Nurses aim to prevent pressure ulcers.

PMID- 7585783
TI  - Clinical pathways: a way to improve quality and reduce cost.

PMID- 7585784
TI  - Care delivery in an alternative site.

PMID- 7585785
TI  - Donor human milk: a gift of life and health.

PMID- 7585786
TI  - An opinion on differentiated practice.

PMID- 7585781
TI  - Panel explores competencies.

PMID- 7585787
TI  - Angel wings.

PMID- 7585789
TI  - Nurses--where have you gone?

PMID- 7585790
TI  - Preparing nursing students for the future.

PMID- 7585791
TI  - What's new in ethics?

PMID- 7585788
TI  - Paradigms--professionalism--paradoxes.

PMID- 7585792
TI  - A winning battle plan.

PMID- 7585794
TI  - A nurse speaks out.

PMID- 7585795
TI  - Independent prescriptive authority for advanced practice nurses.

PMID- 7585793
TI  - What I believe about CNA dues.

PMID- 7585796
TI  - The truth about bedpans and other task.

PMID- 7585797
TI  - Practice changes addressed: update on the Colorado Differentiated Practice Model.

PMID- 7585798
TI  - American Nurses Association denounces AMA action to restrict nurse practitioners.

PMID- 7585799
TI  - One new role for nurses.

PMID- 7585800
TI  - Cardiovascular protection by oestrogen is partly mediated through modulation of
      autonomic nervous function.
AB  - Experimental studies have provided evidence that the autonomic nervous activity
      is modulated by oestrogen. Such modulation at central and peripheral levels tends
      to suppress sympathetic but elevate parasympathetic tone to the cardiovascular
      system. Thus, available data support the view that cardiovascular protection by
      oestrogen may, at least in part, be mediated by its influence on autonomic
      nervous function.

PMID- 7585802
TI  - The promiscuous receptor: a case for the guardian enzyme.

PMID- 7585801
TI  - Sarcoplasmic reticulum function during myocardial ischaemia and reperfusion.

PMID- 7585804
TI  - Vesnarinone inhibits induction of nitric oxide synthase in J774 macrophages and
      rat cardiac myocytes in culture.
AB  - OBJECTIVE: We investigated whether vesnarinone alters the induction of nitric
      oxide (NO) synthesis by bacterial lipopolysaccharide (LPS) or in combination with
      interferon-gamma in cultured J774 macrophages and rat cardiac myocytes. METHODS:
      The induction of NO synthesis was determined by measuring the stable end-product
      nitrite. The cytotoxic effect of vesnarinone was assessed by measuring cell
      respiration. Any change in mRNA levels for NO synthase (NOS) was determined by RT
      PCR. RESULTS: Stimulation by LPS or in combination with interferon-gamma
      increased the accumulation of nitrite in the supernatant of J774 macrophages or
      cardiac myocytes. NOS induction accounted for this accumulation of nitrite, as
      dexamethasone, NG-methyl-L-arginine, and cycloheximide each reduced the
      production of nitrite in both types of cells. Vesnarinone produced a significant
      decline in the cumulative production of nitrite in both types of cells without
      evidence of cytotoxicity. However, the addition of vesnarinone after induction of
      NOS did not inhibit nitrite production. Treatment with LPS or in combination with
      interferon-gamma led to a significant expression of NOS mRNA in both types of
      cells that was significantly reduced by vesnarinone. CONCLUSIONS: Vesnarinone
      inhibited NO synthesis by inhibiting the induction of NOS in J774 macrophages and
      cardiac myocytes. This drug may exert a beneficial effect in patients with heart
      failure, in part, by attenuating the production of NO.

PMID- 7585806
TI  - L-arginine reverses low coronary reflow and enhances postischaemic recovery of
      cardiac mechanical function.
AB  - OBJECTIVE: To evaluate the effect of L-arginine, the physiological substrate of
      nitric oxide (NO), upon coronary flow (CF) and mechanical function during
      reperfusion following cardioplegic arrest. METHODS: Two groups of isolated rat
      hearts were subjected to cardioplegic arrest for 4 h at 4 degrees C. In group 1
      (n = 10) cardioplegic arrest was followed by 4 consecutive periods of reperfusion
      with Krebs buffer (control), Krebs plus L-lysine (1 mmol/1), Krebs plus L
      arginine (1 mmol/1) and Krebs plus L-NGmonomethylarginine (L-NMMA), a specific
      inhibitor of NO synthesis, (0.5 mmol/1). In group 2, hearts (n = 8) were perfused
      by Krebs, then L-NMMA, during both pre- and postischaemic periods. In group 3,
      hearts (n = 8) were perfused by Krebs, then L-arginine (1, 2 and 4 mmol/1). In
      group 4 (n = 5), NO released into the perfusate was measured before ischaemia and
      during reperfusion. RESULTS: In group 1, L-arginine enhanced the postischaemic CF
      (ml/min +/- s.e.m.) from 15.0 +/- 0.4 to 17.2 +/-0.4. This was reduced by L-NMMA
      to 11.3 +/- 0.3. Postischaemic cardiac output (% of preischaemic value +/-
      s.e.m.) was increased from 55.8 +/- 2.4 to 80.1 +/- 2.5 by L-arginine and dropped
      to 54.3 +/- 2.3 with L-NMMA. In group 2, the pre- and postischaemic loss of
      coronary flow (CF) by L-NMMA was 51% and 31% respectively. In group 3, L-arginine
      did not modify CF. In group 4 the preischaemic level of NO (in nmol/ml/min) in
      the coronary effluent, measured by chemiluminescence, was 14.84 +/- 0.83 and
      dropped significantly (P < 0.05) to levels ranging from 3.80 +/- 0.56 to 4.75 +/-
      0.51 during the postischaemic period. CONCLUSION: Exogenous administration of L
      arginine improves low coronary reflow and postischaemic mechanical function.

PMID- 7585803
TI  - The electrophysiology of rabbit hearts with left ventricular hypertrophy under
      normal and ischaemic conditions.
AB  - OBJECTIVES: To examine the cardiac electrophysiological effects of left
      ventricular hypertrophy (LVH) and to determine whether any observed differences
      are modified by global zero-flow ischaemia. METHODS: LVH was induced by
      perinephritic hypertension in New Zealand White rabbits. Transmembrane action
      potential recordings were made using conventional floating glass microelectrodes
      and effective refractory periods (ERP) determined by programmed stimulation in
      isolated arterially perfused interventricular septa during normal perfusion and a
      30-min period of global ischaemia. The electrophysiological data were pooled into
      6-min periods during ischaemia. RESULTS: The post-operative blood pressure was
      76(2) mmHg (mean(s.e.m.)) and 113(2) mmHg (P < 0.0005) in the sham and
      perinephritic rabbits respectively. The left ventricular to body weight ratio was
      0.27(0.01) g kg-1 in the sham and 0.36(0.02) g kg-1 in the perinephritic group (P
      < 0.005) representing 33% hypertrophy. In the isolated septa, prior to ischaemia,
      the hypertrophied group exhibited significant prolongations in action potential
      duration to 50% and 90% repolarisation (APD50, APD90) and ERP of 20%, 12% and 19%
      respectively (P < 0.005) without any differences in resting membrane potential
      (Em), upstroke velocity (dV/dtmax) or amplitude (APA) of the action potential.
      During ischaemia Em, APA and dV/dtmax progressively decreased to a similar extent
      in both groups. Ischaemia resulted in shortenings in APD50, APD90 and ERP in the
      hypertrophy group of 122(9) ms, 131(8) ms and 99 (6) ms respectively which were
      greater than those observed in the control group (84 (7) ms, 115 (7) ms and 50
      (13) ms, P < 0.05). These differences resulted in loss of the preischaemic
      prolongation of repolarisation and refractoriness in the hypertrophy group.
      CONCLUSIONS: There was enhanced shortening of APD and ventricular refractoriness
      in hypertrophied muscle during global ischaemia. This could increase the
      dispersion of repolarization and refractoriness between normal and ischaemic
      hypertrophied muscle during regional ischaemia which may explain the increased
      susceptibility of hypertrophied hearts to arrhythmias.

PMID- 7585805
TI  - Endothelin-1 is not involved in serotonin-induced coronary spasm in a swine
      model.
AB  - OBJECTIVES: The role of endothelin-1 (ET-1) in the pathogenesis of coronary
      artery spasm is not well understood. We aimed to determine if ET-1 is involved in
      serotonin-induced coronary spasm in the swine model. METHODS: In 10 miniature
      pigs, a segment of the left anterior descending coronary artery was denuded and
      irradiated with X-ray. Three months after endothelial denudation, coronary
      vasomotion was assessed in vivo by quantitative arteriography. RESULTS:
      Intracoronary serotonin at 10 micrograms/kg provoked coronary spasm (augmented
      narrowing of the luminal diameter) at the denuded site (diameter reduction 93 +/-
      4%) but not at the non-denuded control site (19 +/- 4%, P < 0.01) associated with
      ST segment elevation in the region perfused by the denuded artery. Intracoronary
      administration of ET-1 at 25 ng/kg caused mild vasoconstriction of the denuded
      (26 +/- 4) and non-denuded site (16 +/- 3%, n.s.), but provoked ST segment
      elevation in the regions perfused by both the denuded and non-denuded arteries.
      The treatment with an endothelin antagonist (BQ123 0.1 mg/kg) significantly
      attenuated coronary vasoconstriction and ST segment elevation evoked with ET-1,
      but did not alter serotonin-induced vasoconstriction either at the denuded or
      control site. CONCLUSIONS: The results of this study suggest that endogenous ET-1
      may not be involved in the pathogenesis of serotonin-induced coronary spasm in
      our swine model.

PMID- 7585807
TI  - Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show
      insulin resistance in the hypertensive rat heart.
AB  - OBJECTIVES: Insulin resistance in skeletal muscle and adipose tissue often
      accompanies hypertension; however, it has not been shown that heart muscle is
      similarly affected. The aims of this study were to determine whether basal and
      insulin-stimulated glucose transport and glucose transporter mRNA content are
      altered in the spontaneously hypertensive rat (SHR) heart. METHODS: Hearts from
      16-18-month-old SHRs were compared to their normotensive (WKY) controls. The
      accumulation of 2-deoxyglucose-6-phosphate (2DG6P), detected using 31P nuclear
      magnetic resonance spectroscopy, was used to assess glucose uptake before and
      during insulin stimulation in the isolated perfused heart. The mRNA levels of
      both the insulin-sensitive glucose transporter (GLUT-4) and the transporter
      responsible for basal glucose uptake (GLUT-1) were quantified by Northern blot
      analysis. RESULTS: The hypertensive rat hearts exhibited hypertrophy in that the
      heart/body weight ratio was increased by 59%. In these hearts, the basal rate of
      glucose uptake was 3-fold greater and hexokinase activity was 1.6 fold greater
      than that of the control rat hearts. On exposure to insulin, accumulation of
      2DG6P increased 5-fold in the control hearts, but only 1.4-fold in the SHR
      hearts. Thus, in the presence of insulin, the rate of glucose uptake by the
      hypertensive rat heart was significantly (P < 0.05) reduced, being 82% of
      control. GLUT-4 mRNA content was decreased was no significant difference in the
      GLUT-1 mRNA content. CONCLUSION: We have demonstrated insulin resistance in the
      hypertrophied heart of the hypertensive rat that may have a molecular basis in a
      lower GLUT-4 content.

PMID- 7585808
TI  - Intracellular calcium transients underlying interval-force relationship in whole
      rat hearts: effects of calcium antagonists.
AB  - OBJECTIVES: Much of the understanding about the cardiac interval-force
      relationship of the whole heart, including mechanical restitution and
      postextrasystolic potentiation (PESP), has been inferred from isolated muscle
      studies. We tested whether results from isolated muscles about intracellular
      Ca2+([Ca2+]i) transients underlying the interval-force relationship can be
      substantiated in whole hearts. Additionally, we investigated whether Ca2+
      antagonists could alter [Ca2+]i transients underlying mechanical restitution and
      postextrasystolic potentiation. METHODS: [Ca2+]i transients were studied in
      isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer
      controlled pacing protocols, we performed restitution curves for left ventricular
      developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a
      function of extrasystolic intervals). To quantify restitution curves, we fitted
      monoexponential functions to plots and analyzed their shift and slope. Then, we
      used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify
      restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as
      Ca2+ released from the sarcoplasmic reticulum. RESULTS: Interval-dependent
      changes in developed pressure were strongly correlated to interval-dependent
      changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts.
      Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not
      to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP
      increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of
      PESP on developed pressure was blunted by high concentrations of Ca2+
      antagonists. CONCLUSIONS: The results from isolated muscles about [Ca2+]i
      transients underlying the interval-force relationship could be substantiated in
      whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o)
      decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not
      change the release kinetics. On the other hand, PESP presumably accelerated Ca2+
      release kinetics of the sarcoplasmic reticulum.

PMID- 7585809
TI  - Evidence for the involvement of the ATP-sensitive potassium channel in a novel
      model of hypoxic preconditioning in dogs.
AB  - OBJECTIVES: The major aims of the present study were to determine if a 5 min
      period of hypoxic (pO2 = 30-40 mmHg) buffer perfusion of the left anterior
      descending (LAD) coronary artery 10 min prior to a 60-min LAD occlusion produces
      myocardial preconditioning (PC) and to determine if hypoxic PC is mediated via
      activation of ATP-sensitive potassium channels (KATP). Normoxic (pO2 = 500-600
      mmHg) buffer perfusion served as a control. METHODS: Barbital-anesthetized dogs
      were subjected to 60 min of LAD occlusion followed by 3 h of reperfusion. Hypoxic
      PC was produced by 5 min of LAD perfusion with hypoxic buffer followed by 10 min
      of blood reperfusion prior to a 60-min occlusion. A sham PC group, elicited by 5
      min of LAD perfusion with normoxic buffer, served as a control. A final group of
      animals was treated with glibenclamide (0.3 mg/kg i.v.), a specific KATP channel
      antagonist, 15 min prior to hypoxic PC and 3 microM of glibenclamide was also
      added to the hypoxic buffer. Transmural myocardial blood flow (TMBF, ml/min/100
      g) was determined by radioactive microspheres 30 min after the initiation of the
      prolonged 60-min occlusion and infarct size (IF/AAR) as a percent of the area at
      risk (AAR) was determined by triphenyltetrazolium staining. RESULTS: There were
      no significant differences between groups in hemodynamics, AAR, or TMBF. Five
      minutes of perfusion with hypoxic buffer prior to the 60-min occlusion produced a
      marked reduction in myocardial infarct size as compared to control animals
      (control, 30 +/- 7 to 9 +/- 2%, hypoxic PC, P < 0.05). Five minutes of perfusion
      with normoxic buffer had no effect on infarct size (30 +/- 6%) and pretreatment
      with glibenclamide completely blocked the protective effect of hypoxic PC (31 +/-
      7%). CONCLUSIONS: These results support the hypothesis that a brief period of
      hypoxic buffer perfusion can precondition the heart and that this
      cardioprotective effect is dependent on the opening of myocardial KATP channels.

PMID- 7585811
TI  - Sodium nitroprusside does not influence tissue oxygen extraction capabilities
      during a critical reduction in oxygen delivery.
AB  - By its regulating effects on blood vessel tone, nitric oxide (NO) may play an
      important role in the coupling of oxygen delivery (DO2) to metabolic rate. We
      reasoned that if endogenous NO synthesis is an important modulator of oxygen
      extraction ratio (O2ER), then administration of a NO donor will alter oxygen
      extraction capabilities during a fall in blood flow. We studied the effects of
      the NO donor, nitroprusside, on the relationship between DO2 and oxygen uptake
      (VO2) during an acute reduction in DO2 induced by cardiac tamponade. Twenty-one
      healthy, anaesthetised, mechanically ventilated dogs were randomly divided into 3
      groups. Group 1 (n = 7) served as control; Groups 2 and 3 were given sodium
      nitroprusside at 1.0 microgram/kg.min (n = 7), and 2.5 micrograms/kg.min
      intravenously (n = 7), respectively. All animals were given normal saline i.v. at
      a rate of 20 ml/kg.h throughout the study. Cardiac tamponade was induced by bolus
      injections of normal saline into the pericardial space. In the control animals
      the critical DO2 (DO2crit) was found at 10.1 +/- 1.5 ml/kg.min and critical O2ER
      (O2ERcrit) at 63.3 +/- 10.9%. Nitroprusside at the lower dose decreased systemic
      vascular resistance but did not significantly influence arterial pressure,
      cardiac output, DO2 or VO2; neither DO2crit nor O2ERcrit was altered (9.3 +/- 2.9
      ml/kg.min and 70.4 +/- 20.9%). Nitroprusside at the higher dose induced
      significant decreases in mean arterial pressure and systemic vascular resistance,
      but had no significant effect on cardiac output. DO2crit (9.2 +/- 2.0 ml/kg.min)
      and O2ERcrit (59.8 +/- 13.2%) were similar to the control group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7585810
TI  - Cardiac angiotensin converting enzyme overproduction indicates interstitial
      activation in renovascular hypertension.
AB  - OBJECTIVES: Angiotensin converting enzyme (ACE) activity in the plasma does not
      change significantly with hypertension in two-kidney, one-clip hypertensive (2K
      1C) rats. However, heart ACE activity and mRNA increase with hypertension. We
      measured the ACE activity and mRNA in hypertrophied hearts at different times
      after clipping, and determined the cellular distribution of its increase in the
      left ventricle of 2K-1C hypertensive rats. METHODS: Cardiac ACE activity was
      quantified in left and right ventricles using a radiolabeled synthetic ACE
      substrate, and ACE mRNA steady-state level was quantified by ribonuclease
      protection assay. Tissue localization of ACE in normal and hypertrophied hearts
      was determined by measuring ACE activity in isolated ventricular cells. In situ
      hybridization with a rat ACE cDNA and immunohistochemistry with a monoclonal anti
      ACE antibody were used to identify tissue compartments producing ACE mRNA and
      protein. RESULTS: The left ventricle was hypertrophied 2 weeks after clipping and
      remained hypertrophied at 12 weeks. Left ventricular ACE activity was
      significantly increased 2 and 4 weeks (3.2 +/- 0.3 in 2K-1C vs. 1.7 +/- 0.1
      pmol/mg prot/min in sham-operated rat) after renal artery clipping, but not at 12
      weeks. The right ventricle was slightly hypertrophied 4 weeks after clipping and
      remained hypertrophied at 12 weeks. Right ventricular ACE activity was
      significantly increased at 4 (6.7 +/- 0.6 in 2K-1C vs. 3.1 +/- 0.3 pmol/mg
      prot/min in sham-operated rat) and 12 weeks. ACE activity was not detectable in
      cardiomyocytes isolated by Percoll gradient. Neither was ACE mRNA detected in
      isolated cardiomyocytes, even after ACE mRNA amplification by RT-PCR. In
      contrast, ACE activity and mRNA were detected in pooled non-cardiomyocytic cells.
      Thus the increase in cardiac ACE activity associated with hypertension must be
      due to an increase in ACE expression by non-cardiomyocytic cells. In situ
      hybridization showed an autoradiographic signal for ACE mRNA over the endothelial
      cells of coronary arteries and over the interstitial spaces including
      pericoronary and fibrosis areas. Immunohistochemistry confirmed these data,
      showing ACE on endothelial cells and in pericoronary spaces with an increased
      signal in pericoronary and fibrosed areas in hypertensive hypertrophied left
      ventricle. CONCLUSION: Besides its usual endothelial expression, ACE is absent
      from cardiomyocytes and present in interstitial tissue, in the pericoronary
      spaces in normal tissue and more markedly in hypertrophied ventricles.

PMID- 7585812
TI  - Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced
      intimal thickening in miniature pigs.
AB  - OBJECTIVE: X-irradiation is known to enhance atherosclerotic change. We tested
      whether coronary vasoconstrictor responses are augmented at the sites of X-ray
      induced intimal thickening in Gottingen miniature pigs. METHODS: In 17 pigs, a
      major branch of the left coronary artery was denuded with a balloon catheter. In
      10 pigs, the denuded portion of the left coronary artery was selectively
      irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group
      1). The remaining 7 pigs were not irradiated (group 2). The effects of
      intracoronary administration of serotonin, histamine and phenylephrine on the
      coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After
      the angiographical study at 5M, the vessels were isolated and isometric tension
      was measured in an organ chamber. RESULTS: The percent reduction in coronary
      diameter evoked with 10 micrograms.kg-1 of serotonin increased from 39(s.e.m. 4)%
      before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P <
      0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M[ [39(6)%
      at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was
      frequently accompanied by ischemic ECG changes. Histamine (10 micrograms.kg-1)
      induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M
      vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group
      2[52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable
      contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated
      serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro
      studies, endothelium-dependent relaxation to serotonin was impaired at the
      denuded site with (group 1) and without (group 2) X-irradiation to a similar
      extent. Isometric tension of medial smooth muscle developed by serotonin was
      significantly greater at the denuded site with X-irradiation (group 1) than the
      control site and the denuded site without X-irradiation (group 2) (P < 0.05).
      Intimal thickening was significantly greater at the denuded sites with X
      irradiation [group 1, 238(45) microns] than at the denuded sites without X
      irradiation [group 2, 58(5) microns] (P < 0.05). CONCLUSIONS: These results
      indicate that X-irradiation augments the coronary vasoconstrictor responses to
      autacoids, predominantly to serotonin, and that this augmentation is accompanied
      by enhanced intimal thickening. Serotonin-induced hypercontraction after X
      irradiation resulted mainly from the hyperreactivity of medial smooth muscle.

PMID- 7585814
TI  - Immunohistochemical evaluation of the developing outflow tract in the rat:
      achieving aortic to mitral fibrous continuity.
AB  - OBJECTIVES: To study the development of aortic to mitral fibrous continuity in
      the normal rat heart. METHODS: The hearts and great vessels of normally developed
      rat embryos and fetuses aged between 13.25 and 19.75 days of gestation were
      studied in conjunction with those of newborns aged 2 and 7 days post-partum.
      Standard histological methods and monoclonal antibodies raised against alpha
      smooth muscle actin (clone 1A4) and ventricular beta myosin heavy chain were used
      to demonstrate the ventricular outlets, ventriculo-arterial junction, inner heart
      curve and aortic infundibulum from the early stages of aortopulmonary septation
      to attainment of their definitive morphology. RESULTS: The two antibodies
      demonstrated temporal specificity (actin specificity increased post-partum;
      myosin specificity maximal during fetal period) in the labelling of their
      intended structures which correlated with their known developmental profile. Full
      thickness fibrous continuity between aortic and mitral valves was not complete
      until 1 week after birth. After ventricular septation was complete, and
      thereafter towards the end of fetal life and beyond, separation was maintained by
      a muscular structure histologically identical to the vestigial netro-aortic root
      branch of the conduction tissue, a structure known to be derived from the
      primitive ventricular myocardium within the environs of the inner heart curve.
      CONCLUSIONS: Ventricular septation (occurring relatively early) and the
      attainment of fibrous continuity (occurring relatively late in development) are
      two independent processes. Muscular tissue separating left-sided arterial and
      atrioventricular valves is not derived from the aortic infundibulum but from the
      inner heart curve. Persistence of this structure is a feature of normal rat heart
      development and needs to be recognised when working with rodent-based animal
      models of congenital heart disease aimed at studying the disruption of the
      development of the ventricular outflow tracts.

PMID- 7585816
TI  - Cell geometry and contractile abnormalities of myocytes from failing human left
      ventricle.
AB  - OBJECTIVES: Systolic and diastolic dysfunction of the failing human heart may be
      due to changes in myocyte function, or to extracellular influences such as
      necrosis, fibrosis or repositioning of viable cells. In order to determine the
      contribution of cellular factors we have characterised the contraction
      amplitudes, and contraction and relaxation velocities of single myocytes isolated
      from failing human left ventricle. METHODS: Myocytes were enzymatically isolated
      from the left ventricles of 42 subjects, superfused at 32 degrees C and paced at
      0.2 Hz. Using a video/edge tracking system we obtained contraction amplitude and
      contraction and relaxation velocities as well as times to peak contraction (TTP)
      and to 50% and 90% relaxation (R50 and R90). Concentration-response curves to
      Ca2+ were constructed for each cell. RESULTS: There was little difference in
      contraction amplitude at any Ca2+ concentration between cells from failing and
      non-failing hearts at this low frequency. At maximally activating Ca2+
      concentrations (6-20 mM) there was a 30% slowing of relaxation velocity in
      myocytes from patients with both mild-moderate (P < 0.001) and severe (P < 0.001)
      congestive heart failure. Contraction and relaxation times were increased in
      myocytes from failing hearts [TTP: 0.46 +/- 0.02 s (n = 34 patients) vs. 0.35 +/-
      0.02 s (n = 6), P < 0.01 and R50: 0.25 +/- 0.02 s (n = 34) vs. 0.16 +/- 0.02 s (n
      = 6), P < 0.001]. Impaired relaxation was seen with most etiologies, including
      ischemic and dilated cardiomyopathies and mitral valve disease. Myocytes from
      failing hypertrophied ventricles were more severely affected than those from
      failing non-hypertrophied hearts for both contraction and relaxation velocities.
      Cells from failing hypertrophied ventricles had a significantly larger area than
      from non-failing or failing non-hypertrophied ventricles, although cell length
      and sarcomere length were similar between groups. Larger myocytes did not show a
      more pronounced change in relaxation velocity than normally sized cells from the
      same hypertrophied ventricle. CONCLUSIONS: Significant impairment of relaxation
      can be observed in ventricular myocytes from failing human heart under conditions
      where contraction amplitude appears normal. The defect is not confined to one
      etiology of disease, but is exacerbated during hypertrophy. An increase in cell
      size, although observed in myocytes from hypertrophied ventricle, does not itself
      account for changes in relaxation. Cellular changes contribute to diastolic
      dysfunction in the failing human heart.

PMID- 7585813
TI  - In vitro oxidative damage to tissue-type plasminogen activator: a selective
      modification of the biological functions.
AB  - OBJECTIVE: Tissue-type plasminogen activator (t-PA) is an important component of
      the blood fibrinolytic system responsible for thrombus dissolution. It is often
      required to function under oxidative stress, and exogenous t-PA is used
      clinically in the treatment of acute myocardial infarction (AMI). The aim of this
      study was to examine alterations in the residual activity of t-PA pre-treated
      with certain oxidants. METHODS: Recombinant t-PA (rt-PA) and native t-PA (nt-PA)
      were pre-treated with freshly generated hypochlorous acid (HOCl) and chloramine T
      at varying concentrations. The amidolytic activity, the plasminogenolytic
      activity and the fibrin-binding affinity were then examined using chromogenic
      assays based on S-2288 and S-2251. RESULTS: The amidolytic activity of t-PA was
      surprisingly found to be rather sensitive (IC50 1 and 12 mumol/1, respectively),
      and the plasminogenolytic activity rather resistant to pre-treatment with HOCl
      and chloramine T. The fibrin binding study of treated t-PA revealed substantial
      loss of binding to CNBr-digested fibrinogen (FDP-CNBr). The velocity of t-PA in
      reaction with plasminogen remained the same as non-treated t-PA. The possible
      mechanisms of this asymmetrical oxidative modification of the biological
      functions are also discussed. CONCLUSIONS: (1) The catalytic activity of t-PA and
      the binding affinity for its large-molecule substrate plasminogen, rather than
      the small-molecule substrate S-2288, are highly resistant to oxidative damage;
      (2) the fibrin-binding affinity of t-PA can be selectively and asymmetrically
      damaged by exposure to these oxidants. Thus it is possible that the
      characteristic advantage of thrombus selectivity of t-PA in both spontaneous
      thrombolysis and thrombolytic therapy may be diluted in circumstances where toxic
      and reactive oxidants exist.

PMID- 7585817
TI  - Angiotensin-II-induced increase in transcoronary protein clearance: role of
      hypertension vs. nitric oxide or cyclo-oxygenase products.
AB  - Elevations in plasma angiotensin II (AngII) are associated with an efflux of
      plasma macromolecules into the perivascular and contiguous interstitial space.
      Whether this exudative response is related to associated hypertension or another
      effect of AngII is uncertain. We therefore monitored plasma and cardiac lymph
      total protein, albumin and fibronectin and calculated transvascular clearances
      for total protein (TVPC) and albumin (TVAC) and lymph fibronectin transport (LFT)
      every 30 min in open-chested, instrumented dogs. After baseline observations were
      obtained over 30 min, pressor (250 ng.kg.min-1) or nonpressor (11 ng.kg.min-1)
      doses of AngII were given intravenously for 90 min. Saline-treated, instrumented
      dogs served as controls. To address a potential secondary effect of AngII on
      vascular protein clearance, we monitored lymph prostaglandin E2 and cGMP (a
      marker of released nitric oxide, NO). At > or = 30 min, each dose of AngII was
      associated with a significant (P < or = 0.05) and comparable increase in TVPC,
      TVAC and LFT over baseline, indicating that increase in protein clearance was not
      related to elevated arterial pressure. Lymph cGMP rose significantly (P < or =
      0.05) at 30 min for each dose of AngII and remained elevated thereafter. Lymph
      PGE2 was increased at > or = 60 min (P < or = 0.05) but only with the pressor
      dose. To determine the contribution of NO and PGE2 on AngII-induced transcoronary
      protein clearance, each dose of AngII was accompanied by co-administration of
      either the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or
      the cyclo-oxygenase inhibitor, indomethacin. L-NAME completely inhibited the
      release of cGMP and the increase in protein clearance was not seen. Indomethacin
      suppressed the release of PGE2, but did not prevent the increase in protein
      clearance. Thus, AngII-induced increase in transcoronary protein clearance is not
      related to arterial hypertension or the release of PGE2, but instead appears to
      be mediated by NO release.

PMID- 7585818
TI  - Effects of OPC-18790, a new positive inotropic agent, on energetics in the
      ischaemic canine heart: a 31P-MRS study.
AB  - OBJECTIVE: Effects of OPC-18790, a novel positive inotropic agent, on
      cardiohaemodynamics and cardiac energetics were assessed simultaneously in dogs
      with cardiac ischaemia using phosphorus-31 magnetic resonance spectroscopy (31P
      MRS) and compared with those of amrinone, a pure cGMP-inhibited PDE inhibitor.
      METHODS: Cardiac ischaemia was produced by partial stenosis of the coronary
      artery. Dogs with cardiac ischaemia were instrumented for the determination of
      regional coronary blood flow (non-radioactive coloured microsphere method),
      regional contractile function (sonomicrometry), and haemodynamics. Myocardial
      phosphate compounds were measured simultaneously by 31P-MRS. RESULTS: Coronary
      stenosis produced regional dyskinesis, a slight decrease in cardiac output (CO),
      intracellular acidosis, an increase in the inorganic phosphate (Pi)/creatine
      phosphate (PCr) ratio concomitantly with a decrease in regional coronary blood
      flow (CBF) in the ischaemic region. OPC-18790 dose-dependently produced an
      increase in contractility (measured by peak LVdP/dt) and CO, with only slight
      changes in heart rate (HR) and mean blood pressure (mBP). OPC-18790 did not
      change regional dyskinesis, but improved the Pi/PCr ratio at the high dose
      compared with ischaemic values (before drug administration). Amrinone produced an
      increase in CO comparable to that of OPC-18790; however, the increase in peak
      LVdP/dt was smaller while the increase in HR and decrease in mBP were larger than
      those seen with OPC-18790. Amrinone worsened the Pi/PCr ratio and intracellular
      acidosis only at the high dose. CONCLUSION: These observed differences in energy
      metabolism between OPC-18790 and amrinone at the high dose may be due to the
      ability of OPC-18790 to increase CBF in the ischaemic region and which may
      attributed to its differing effect on overall haemodynamics. Thus, OPC-18790 may
      be useful in the management of ischaemic heart failure.

PMID- 7585820
TI  - The pacemaker current (I(f)) does not play an important role in regulating SA
      node pacemaker activity.

PMID- 7585815
TI  - Acute and chronic effects of transient myocardial ischemia on sympathetic nerve
      activity, density, and norepinephrine content.
AB  - OBJECTIVES: The sympathetic nervous system has profound influences on myocardial
      function, particularly during ischemia. There is controversy, however, as to
      whether myocardial ischemia results in damage to myocardial sympathetic nerves
      coursing through the ischemic territory. To further evaluate these issues, we
      assessed the acute and chronic effects of transient myocardial ischemia on
      sympathetic nerve function and morphology. METHODS: A total of 20 dogs were
      studied. For acute studies (n = 9), we performed serial dynamic imaging of I-123
      metaiodobenzylguanidine (MIBG) washout during coronary occlusion and reperfusion,
      and assessed residual myocardial perfusion with thallium-201. For chronic studies
      (n = 11), we assessed sympathetic innervation and perfusion 11 days following a
      transient intracoronary balloon occlusion. Imaging results were correlated with
      electrocardiographic responses, histology, and tissue norepinephrine (NE).
      RESULTS: In the acute studies, regional MIBG washout increased more than 2-fold
      in the ischemic territory compared to the control region during coronary
      occlusion (14.2 +/- 2.3 vs. 5.9 +/- 1.2%, P < 0.01). Tissue NE was reduced in the
      ischemic territory compared to the non-ischemic territory (335 +/- 162 vs. 751 +/
      190 ng/g, P < 0.01). Myocardial perfusion was normal. In the chronic studies,
      9/11 dogs showed ischemic ECG changes during balloon occlusion, and developed
      ventricular arrhythmias. On follow-up imaging, 5/11 dogs showed reduced MIBG
      uptake relative to thallium, in viable myocardium overlying necrotic
      subendocardium, reduced NE (226 +/- 77 vs. 733 +/- 82 ng/g in control regions, P
      < 0.01), decreased nerve density, and a larger extent of denervation than scar
      (25.5 +/- 3.7 vs. 8.2 +/- 2.7%, P < 0.02). Six of 11 dogs showed normal
      innervation patterns. CONCLUSIONS: These studies suggest that the sympathetic
      nerves are acutely affected in regions of myocardial ischemia as detected by
      enhanced regional washout of MIBG. In addition, chronic sympathetic nerve
      denervation can occur in the absence of transmural myocardial necrosis; however,
      the occurrence of transient ischemia does not predict the development of chronic
      denervation. The severity of ischemia, as evidenced by the extent of the related
      necrosis, does appear to predict chronic denervation. The severity of ischemia,
      as evidenced by the extent of the related necrosis, does appear to predict
      chronic denervation. The mechanisms leading to chronic denervation of sympathetic
      nerves in the absence of transmural infarction remain to be defined.

PMID- 7585819
TI  - The pacemaker current (I(f)) plays an important role in regulating SA node
      pacemaker activity.

PMID- 7585822
TI  - Role of peripheral autonomic neurones in maintaining adequate cardiac function.
AB  - This review has focused on the putative effects that peripheral autonomic
      neurones exert on cardiac myocytes. Through data obtained by the use of in situ
      and in vitro models, the unique synaptology and chemical sensitivities of the
      various types of neurones in intrinsic cardiac and extracardiac intrathoracic
      ganglia are becoming evident. The intrathoracic nervous system acts as a
      distributive network, processing in a complex fashion information that arises not
      only from cardiac, vascular and pulmonary tissues but also from extrathoracic
      tissues, to maintain adequate cardiac function. In challenging the current
      understanding of cardiac regulation, this view provides novel opportunities to
      develop pharmacological and surgical strategies to manipulate cardiac function in
      disease states.

PMID- 7585821
TI  - Ion channels, oxygen sensation and signal transduction in pulmonary arterial
      smooth muscle.
AB  - In contrast to systemic arteries those of the pulmonary circulation constrict in
      response to hypoxia: a mechanism known as "hypoxic pulmonary vasoconstriction"
      (HPV). It is has been established that changes in alveolar oxygen tension are the
      primary stimulus for triggering HPV. The mechanisms underlying this unique
      response are unknown. Neither the role of the endothelium nor that of the smooth
      muscle of the pulmonary arteries in oxygen sensing has been elucidated, although
      both tissues may be involved. Evidence is accumulating to suggest that K+
      channels located in the plasma membranes of pulmonary arterial smooth muscle
      cells may play an important role in oxygen sensing. This process may involve
      novel mechanisms of signal transduction and K+ channel regulation by charged
      intermediates, redox reactions or membrane-delimited factors.

PMID- 7585823
TI  - Altering the topology of gap junctions a major therapeutic target for atrial
      fibrillation.

PMID- 7585824
TI  - Prostaglandin-mediated inhibition of nitric oxide production by bovine aortic
      endothelium during hypoxia.
AB  - OBJECTIVE: The present study utilized a monoculture of vascular endothelium to:
      (1) determine if nitric oxide (NO) production was decreased during hypoxia, (2)
      ascertain if specific prostaglandins were released in response to hypoxia, and
      (3) determine if cyclo-oxygenase inhibition would modulate hypoxia-induced
      decreases in NO production. METHODS: Bovine aortic endothelial cells (BAE cells)
      were grown to confluence on microcarrier beads. NO released in response to the
      receptor-independent agonist, A23187 calcium ionophore, was directly and
      continuously measured using a sensitive and specific chemiluminescence method.
      Cells were exposed to either "hypoxia" (pO2 = 10 mmHg) or "normoxia" (pO2 = 160
      mmHg) for 30 min. NO was quantitatively measured with and without indomethacin
      (1.7 microM) in the incubation medium, and also following incubation with the
      prostacyclin analog, iloprost. The prostaglandins PGI2 and PGE2 released in
      response to hypoxia were quantitated using an enzyme immunoassay. RESULTS:
      Hypoxia significantly decreased NO production, resulting in a 22.8(2.1)%
      reduction in NO from 94.3(5.3) nmol/micrograms protein (during normoxia) to
      73.5(2) nmol/micrograms protein (during hypoxia). Hypoxia significantly
      stimulated the production of PGI2 and PGE2, in excess of that released in
      response to A23187 when compared with normoxia. Following cyclo-oxygenase
      inhibition, the hypoxia-induced decrease in NO production was abolished (0.13
      [2.7] % change relative to controls). Furthermore, iloprost (10 nM) directly
      inhibited NO production. CONCLUSIONS: The results demonstrate that ionophore
      stimulated NO production is sensitive to oxygen tension, decreasing in response
      to hypoxia. Inhibition of prostaglandin synthesis restores NO production during
      hypoxia, while iloprost directly suppresses NO production. Thus, endothelium
      derived prostanoids produced in response to hypoxia may modulate NO production
      via an autocrine negative feedback mechanism.

PMID- 7585825
TI  - Myocardial interstitial purine metabolites and lactate with increased work in
      swine.
AB  - OBJECTIVE: Dobutamine stimulates the beta-receptors in the heart and increases
      myocardial blood flow and oxygen consumption 2-3-fold, similar to effects seen
      with exercise. The purpose of this study was to assess temporal changes in
      myocardial interstitial purine metabolites, adenosine monophosphate (AMP) and
      lactate during and following 30 min of dobutamine infusion. METHODS: Dobutamine
      (15 micrograms/kg/min) was infused via the jugular vein into 9 anesthetized, open
      chest, domestic swine. Interstitial fluid was sampled with microdialysis probes
      placed in the midmyocardium. The effluent from the probes, referred to as the
      dialysate, was used to estimate myocardial interstitial purine metabolites, AMP,
      and lactate levels before, during, and following a dobutamine-induced increased
      work state. RESULTS: Dobutamine infusion resulted in a 77% increase in heart
      rate, a 258% increase in left ventricular dP/dt, a 208% increase in myocardial
      oxygen consumption, and a 155% increase in rate x pressure product. Myocardial
      blood flow was increased in the subepicardium, midmyocardium, and subendocardium
      by 207, 268, and 268%, respectively, compared to the control period. Neither
      coronary venous nor dialysate lactate concentrations changed throughout the
      protocol. Dialysate adenosine and AMP levels were both significantly elevated (P
      < 0.05) during the dobutamine period and fell back to control values during the
      recovery period. CONCLUSIONS: The dobutamine-induced increases in myocardial
      oxygen consumption, rate x pressure product, and blood flow, without an increase
      in coronary venous or interstitial lactate suggest that energy balance is
      maintained during dobutamine infusion. Thus an increase in myocardial work, in
      the absence of demand-induced ischemia, resulted in accumulation of adenosine and
      AMP in the interstitium.

PMID- 7585826
TI  - Effects of thapsigargin on aequorin-injected and skinned preparations of ferret
      ventricular muscles.
AB  - OBJECTIVE: We investigated the effects of thapsigargin (TG) (0.1-1 microM) on the
      relation between intracellular Ca2+ concentration and tension in ferret papillary
      muscles using aequorin-injected and skinned preparations. METHODS: Aequorin was
      injected into the superficial cells of ferret papillary muscles; the Ca2+ signals
      of aequorin and tension in twitch and those with the application of 15 mM
      caffeine were simultaneously measured. The alteration of Ca2+ sensitivity of the
      contractile elements was examined by measuring the pCa-tension relation in Triton
      X-treated skinned preparations. RESULTS: TG decreased the peak of the Ca2+ signal
      accompanied by a prolonged decay time. However, the tension was scarcely altered
      even at 1 microM TG. TG inhibited the caffeine-induced Ca2+ signal. Prolongation
      of decay of the Ca2+ signal by TG in twitch was further enhanced by isoprenaline
      (10 nM). The pCa-tension relation of the skinned preparation was slightly but
      significantly shifted to the right by TG. CONCLUSIONS: The apparent dissociation
      of the effects of TG on the Ca2+ signal and tension in intact preparations is not
      a result of alteration of the Ca2+ sensitivity of the myofilaments. The effects
      of TG in multicellular preparations are probably limited to the outer layer of
      the preparation. The slower time course of the Ca2+ signal induced by TG is due
      to the inhibition of Ca2+ uptake by sarcoplasmic reticulum, which is more
      significantly observed when the intracellular Ca2+ transient is increased by
      isoprenaline.

PMID- 7585827
TI  - Annexin V is localized in association with Z-line of rat cardiac myocytes.
AB  - OBJECTIVE: The aim of this study was to characterize a 33-kDa protein (p33)
      isolated from bovine liver and to determine the subcellular localization of the
      protein in rat cardiocytes as well as in non-cardiac tissues. METHODS: Cycles of
      calcium-induced precipitation coupled with EGTA-resolubilization were used to
      isolate crude annexins from bovine and rat tissues. Column chromatography was
      performed to purify the p33 from the crude annexins. The protein was identified
      as annexin V by partial amino acid sequence determination. Specificity of anti
      annexin V antibody was examined by using Western blotting after one- or two
      dimensional electrophoresis. For characterization of the protein,
      immunofluorescence microscopy and actin-binding assays were carried out. RESULTS:
      Immunofluorescence microscopy showed that annexin V was stained as a striated
      pattern along myofibrils on frozen sections of both atria and ventricles of adult
      rats. The striations were seen more clearly in cultured rat atrial myocytes.
      Examination of doubly stained cardiocytes with anti-annexin V and anti-alpha
      actinin by a confocal laser scanning microscope suggests that annexin V is
      localized in association with the Z-line of rat cardiac myocytes. We also found
      that annexin V was stained intensely in actin-rich regions of non-cardiac tissues
      such as bile canaliculi of rat liver and brush border-terminal web region in the
      epithelial cells of both small intestine and kidney proximal tubular cells. F
      actin binding experiments revealed that annexin V failed to bind to F-actin
      directly in vitro. CONCLUSION: Our results suggest that annexin V is a new
      component of the Z-line in rat cardiocytes and might be involved in regulation of
      its organization.

PMID- 7585829
TI  - Sarcoplasmic reticulum and myofilament function in chemically-treated ventricular
      trabeculae from patients with heart failure.
AB  - OBJECTIVES: Assessment of sarcoplasmic reticulum calcium-loading ability,
      myofilament force production and myofilament calcium sensitivity in ventricular
      trabeculae from patients with heart failure. METHODS: Right ventricular
      trabeculae (diameter 150-250 microns) were obtained from 18 patients undergoing
      elective cardiac transplantation. These were mounted for isometric tension
      measurement and treated with saponin which permeabilises the sarcolemma leaving
      the sarcoplasmic reticulum (SR) functionally intact. The trabecula was bathed in
      a mock intracellular solution containing ATP and weakly buffered [Ca2+] at
      various concentrations (150-400 nM). The amplitude of caffeine-induced
      contractures was used as a quantitative measure of the SR calcium content and was
      correlated with the clinical severity of heart failure. The same trabecula was
      then exposed to a solution containing Triton-X100 (1%) which destroys all cell
      membranes leaving only the myofilaments intact. The maximum calcium-activated
      force (Cmax) and myofilament responsiveness to calcium was assessed. RESULTS:
      Patients with ischaemic heart disease (IHD) and severe heart failure (PCWP > 20
      mm Hg, ejection fraction < 15%, n = 8) demonstrated low SR Ca(2+)-loading ability
      compared with patients with IHD and moderate heart failure (PCWP-20 mmHg, LV
      ejection fraction > 20%, n = 6). Patients with dilated cardiomyopathy (DCM) (n =
      4) demonstrated SR Ca(2+)-loading ability which was lower than either of the two
      IHD groups. Myofilament force production (per unit cross-sectional area) was not
      significantly different between the three groups. Myofilament responsiveness to
      Ca2+ demonstrated no relationship with severity of heart failure. CONCLUSIONS: In
      human heart failure, SR Ca(2+)-loading ability diminishes with increasing
      severity of heart failure. Myofilament force production and sensitivity to
      calcium are unaffected by severity of heart failure.

PMID- 7585828
TI  - L-NMMA blocks carbachol-induced increases in cGMP levels but not decreases in
      tension in the presence of forskolin in rabbit papillary muscles.
AB  - OBJECTIVE: The purpose of the present investigation was to determine whether
      stimulation of the nitric oxide synthase pathway contributes to the muscarinic
      receptor-mediated elevation in cGMP levels and reversal of the positive inotropic
      response to the adenylyl cyclase activator forskolin in rabbit papillary muscles.
      METHODS: Intact rabbit papillary muscles suspended under tension in isolated
      tissue baths were incubated in the absence or presence of the nitric oxide
      synthase inhibitor L-NG-monomethyl arginine (L-NMMA) and then treated with
      forskolin followed by the muscarinic agonist carbachol. The developed tension of
      the preparations was monitored during their exposure to drug. Papillary muscles
      were then frozen and subsequently assayed for cGMP levels by radioimmunoassay.
      Tension and cGMP levels were also measured in some papillary muscles treated with
      forskolin followed by sodium nitroprusside. RESULTS: Incubation of papillary
      muscles with L-NMMA completely blocked increases in cGMP levels produced by
      carbachol, but had no effect on the reversal by carbachol of the increase in
      tension in response to forskolin. Sodium nitroprusside also caused a marked
      elevation of cGMP levels in rabbit papillary muscle, but had no significant
      effect on the forskolin-induced increase in tension. CONCLUSIONS: These data
      demonstrate that activation of muscarinic receptors results in increases in cGMP
      levels largely through the nitric oxide synthase pathway in rabbit papillary
      muscles. However, the cGMP produced through this pathway or by sodium
      nitroprusside does not appear to contribute to the reversal of the positive
      inotropic response to forskolin.

PMID- 7585830
TI  - Relation between myocardial beta-adrenoceptor density and hemodynamic and
      neurohumoral changes in a rat model of chronic myocardial infarction: effects of
      ibopamine and captopril.
AB  - OBJECTIVES: The purpose of this study was to investigate the changes in beta
      adrenoceptor density (Bmax) and distribution in a model of chronic myocardial
      infarction in rats, and to relate possible changes to hemodynamic and
      neurohumoral abnormalities. In addition, we examined the effects of 8 weeks
      treatment with ibopamine and captopril. METHODS: There were 3 experiments: (1)
      Bmax and plasma catecholamines were examined (n = 46), (2) Bmax was compared in
      infarcted and non-infarcted tissue (n = 13), and (3) contractile function was
      evaluated by isolated heart perfusion (n = 40). Of rats in Expts. (1) and (3),
      50% had myocardial infarction induced by coronary ligation and 50% were controls.
      Each group was divided between ibopamine, ibopamine and captopril, or standard
      (no drug) treatment. RESULTS: Bmax was not decreased in rats with myocardial
      infarction (10.8 +/- 0.8 fmol/mg protein), compared to normal rats (11.4 +/- 0.6
      fmol/mg protein), and the ratio beta 1/beta 2 was also unaffected. In infarcted
      tissue, Bmax was significantly (P = 0.03) lower than in non-infarcted tissue.
      Baseline left ventricular pressure, systolic and diastolic dP/dT were all
      impaired (P < 0.001), and plasma norepinephrine levels were elevated in rats with
      myocardial infarction (16.03 +/- 230 vs. 1287 +/- 83 pg/ml; P < 0.05), compared
      to normals. Both ibopamine alone and in combination with captopril reduced the
      elevated plasma norepinephrine levels in infarcted rats (P < 0.001), but only the
      combination of the 2 drugs significantly increased Bmax in infarcted rats (14.7
      +/- 0.8 fmol/mg protein; P = 0.03 vs. untreated myocardial infarction), while
      ibopamine alone had no significant effect (13.1 +/- 1.1 fmol/mg protein; p = ns).
      Also, active drug treatment had no significant effect on the hemodynamic changes.
      CONCLUSIONS: In this coronary artery ligation model of myocardial infarction in
      rats, no beta-adrenoceptor down-regulation is observed, despite marked
      abnormalities in baseline left ventricular function and plasma norepinephrine
      levels. The combination of ibopamine and captopril significantly increases Bmax
      in infarcted rats, which is accompanied by a reduction in plasma norepinephrine
      levels, but not by an improvement in hemodynamic parameters.

PMID- 7585832
TI  - Fluorescent vs. radioactive microsphere measurement of regional myocardial blood
      flow.
AB  - OBJECTIVES: This study compared simultaneous regional myocardial blood flow
      (RMBF) measurements using fluorescent microspheres (FM) and radiolabeled
      microspheres (RM). The utility of an internal standard during processing was also
      examined. METHODS: Paired FM and RM were injected into the left atrium of 9
      anaesthetised rabbits. RMBF was altered by use of either regional ischaemia or (
      )-N6-(2-phenylisopropyl)-adenosine. Radioactivity of blood reference and tissue
      samples was quantitated using standard methods. Samples were then digested with
      potassium hydroxide and microspheres recovered by vacuum filtration, with an
      additional label of FM as the internal standard. FM labels were extracted using
      Carbitol acetate and quantitated using fluorescence spectroscopy. Agreement
      between the fluorescent and radioactive methods was assessed using both
      orthogonal regression and difference-against-mean analyses. RESULTS: Using
      recovery-uncorrected data, the slope of the orthogonal regression of RM and FM
      determined RMBF was not statistically different from 1, but the intercept was
      statistically different from 0 [-0.03(0.01), P = 0.005] and the mean RMBF by each
      method differed from one another [1.24(0.08) vs. 1.17(0.08) ml.min-1.g-1, P =
      0.0002]. The mean +/- 2 s.d. of the differences of RMBF (RM minus FM) was +0.07
      +/- 0.30 ml.min-1.g-1. Although recovery of FM from tissue averaged 97.6(1.2)%,
      use of the internal standard to correct for losses substantially improved the
      agreement between RM and FM-determined RMBF: the orthogonal regression slope was
      not statistically different from 1, the intercept was not statistically different
      from 0, and the means of the flows were not different. The mean +/- 2 s.d. of the
      differences of RMBF was -0.01 +/- 0.22 ml.min-1.g-1. The internal standard also
      improved RMBF estimates from samples with simulated large spillage during
      processing. CONCLUSION: Fluorescent microspheres are an equivalent alternative to
      radiolabeled microspheres for the estimation of RMBF. Although the overall
      recovery of microspheres using this technique was high, use of an internal
      standard is recommended for correction of random losses.

PMID- 7585831
TI  - Myocardial Ca(2+)- and ATP-cycling imbalances in end-stage dilated and ischemic
      cardiomyopathies.
AB  - OBJECTIVES: We have previously demonstrated deficiencies in myocardial cycling of
      Ca2+, and ATP turnover, in animals with heart failure (HF). The objective of this
      study was to determine the relevance of these changes to human HF. METHODS: We
      used the Ca2+ dye, indo-1, and the Ca(2+)-channel modulator ryanodine to examine
      Ca(2+)-cycling in homogenates containing 2.5% myocardium from 12 patients
      undergoing cardiac transplantations because of ischemic or idiopathic dilated
      cardiomyopathies (ISCM, DCM), and compared them to homogenates from 11 organ
      donors who died from noncardiac causes. Key enzymes of ATP production and
      utilization were also assayed. RESULTS: In HF due to either ISCM or DCM, compared
      to nonfailing myocardium, rate constants (x 10(-3) s-1) for sarcoplasmic
      reticulum Ca(2+)-pumping (41.6 +/- 16.0 versus 15.1 +/- 5.9) and Ca(2+)-channel
      (25.1 +/- 8.3 versus 6.2 +/- 4.1) activities were decreased by 64 and 75%,
      respectively. These changes in rate constants were associated with a three-fold
      increase in ionized Ca2+ concentration. Compared to nonfailing myocardium,
      activities (IU/g) of ATP turnover were also decreased in ISCM and DCM HF by 39%,
      30%, and 34%, respectively, for ATP production capacity of creatine kinase (1830
      +/- 130 versus 1110 +/- 411) and oxidative phosphorylation (20.0 +/- 3.3 and 14.1
      +/- 4.8), and for ATP utilization (28.2 +/- 18.7 versus 18.7 +/- 4.0). Myoglobin,
      a key component of oxidative phosphorylation, was approximately 50% lower with HF
      (1.72 +/- 0.30 versus 0.97 +/- 0.20 mg/g). CONCLUSIONS: As in animal models,
      cycling of Ca2+ and ATP turnover were markedly impaired in human heart failure.
      There were no consistent biochemical differences attributable to difference in
      etiology, excepting that myoglobin deficiency was 33% greater in ISCM than DCM.
      We conclude that ATP and Ca2+ cycling are significantly impaired in human HF due
      to DCM and ISCM.

PMID- 7585833
TI  - Creatine supplementation in chronic heart failure increases skeletal muscle
      creatine phosphate and muscle performance.
AB  - BACKGROUND: Cardiac creatine levels are depressed in chronic heart failure. Oral
      supplementation of creatine to healthy volunteers has been shown to increase
      physical performance. AIM: To evaluate the effects of creatine supplementation on
      ejection fraction, symptom-limited physical endurance and skeletal muscle
      strength in patients with chronic heart failure. METHODS: With a double-blind,
      placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40)
      were supplemented with creatine 20 g daily for 10 days. Before and on the last
      day of supplementation ejection fraction was determined by radionuclide
      angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise
      performance on the cycle ergometer. Muscle strength as unilateral concentric knee
      extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated.
      Skeletal muscle biopsies were taken for the determination of energy-rich
      phosphagens. RESULTS: Ejection fraction at rest and at work did not change.
      Performance before creatine supplementation did not differ between placebo and
      creatine groups. While no change was seen in the placebo group compared to
      baseline, creatine supplementation increased skeletal muscle total creatine and
      creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05),
      respectively. Increments were seen only in patients with < 140 mmol total
      creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged
      performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both
      peak torque and 1-legged performance increased linearly with increased skeletal
      muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak
      torque were significant compared to the placebo group, (P < 0.05). CONCLUSIONS:
      One week of creatine supplementation to patients with chronic heart failure did
      not increase ejection fraction but increased skeletal muscle energy-rich
      phosphagens and performance as regards both strength and endurance. This new
      therapeutic approach merits further attention.

PMID- 7585834
TI  - Ca(2+)-growth coupling in angiotensin II-induced hypertrophy in cultured rat
      cardiac cells.
AB  - OBJECTIVES: There remain some controversies about the effect of angiotensin II on
      intracellular Ca2+ concentration ([Ca2+]i) in cardiac myocytes. The aim of this
      study was to investigate different roles of intracellular Ca2+ in the responses
      to angiotensin II between cardiac myocytes and nonmyocytes. METHODS: Primary
      cultures of neonatal rat cardiac myocytes and nonmyocytes were prepared. [Ca2+]i
      was measured with indo-1. Cellular growth was assayed by [3H]thymidine uptake,
      RNA content, [3H]phenylalanine incorporation and protein content. Induction of
      immediate-early gene was examined by Northern blot analysis. RESULTS: In
      myocytes, angiotensin II decreased [Ca2+]i transients, induced c-fos mRNA, and
      accelerated hypertrophy. These effects were completely suppressed by AT1 receptor
      blockade or protein kinase C inhibition. After chelation of extracellular Ca2+,
      angiotensin II caused no change in [Ca2+]i or no induction of c-fos in myocytes.
      Phorbol 12-myristate 13-acetate also decreased [Ca2+]i transients, caused c-fos
      induction, and provoked hypertrophy in myocytes. In nonmyocytes, angiotensin II
      increased [Ca2+]i transiently, induced c-fos mRNA and hypertrophy. These effects
      of angiotensin II were not fully abolished by protein kinase C inhibition.
      Extracellular Ca2+ chelation did not completely inhibit the effects of
      angiotensin II on [Ca2+]i or c-fos induction in nonmyocytes. Phorbol 12-myristate
      13-acetate did not affect [Ca2+]i or cellular growth in nonmyocytes but did cause
      c-fos induction. CONCLUSIONS: These results suggest that angiotensin II induces
      cellular hypertrophy and immediate-early genes through the activation of protein
      kinase C in myocytes, although angiotensin II decreases [Ca2+]i transients via
      this signaling pathway. Induction by angiotensin II of hypertrophy and immediate
      early genes in nonmyocytes may be in part mediated by a transient increase in
      [Ca2+]i which acts synergistically with protein kinase C activation.

PMID- 7585836
TI  - Depressed transient outward current in single hypertrophied cardiomyocytes
      isolated from the right ventricle of ferret heart.
AB  - OBJECTIVE: The aim of this study was to investigate transient outward potassium
      current (Ito) changes as a basis for the prolongation of the action potential
      associated with cardiac hypertrophy. METHODS: Right ventricular hypertrophy was
      induced by chronic pulmonary artery constriction in adult male ferrets. After 4-6
      weeks, hearts were excised and single myocytes were isolated from the right
      ventricles of banded and sham-operated (control) animals by enzymatic
      dissociation. Ito was recorded by means of the whole cell patch clamp technique.
      RESULTS: Heart weight:body weight ratio and cell membrane capacitance, as
      indications of hypertrophy, were increased by 17% (P < 0.05) and 32% (P < 0.01)
      respectively in the banded group. Analysis of Ito showed that in hypertrophied
      myocytes compared to normal controls: (1) the density of current was
      significantly reduced; (2) both the time to peak and the time constant of
      inactivation were increased; (3) the voltage-dependent steady-state availability
      was not changed, with similar potentials for half activation (30.4 +/- 6.8 mV in
      control and 33.9 +/- 8.5 mV in hypertrophied cells) and half inactivation (-12.3
      +/- 3.3 mV in control and -11.4 +/- 2.7 mV in hypertrophied cells); (4) the time
      constant for recovery from inactivation was significantly increased regardless of
      the holding potentials (-50 mV, -70 mV or -90 mV). CONCLUSIONS: Alterations of
      the transient outward potassium current with respect to its density, kinetics and
      recovery from inactivation can explain the prolongation of the action potential
      in myocytes isolated from pressure-overload hypertrophied heart and may thus be
      an important step in such cardiac adaptation.

PMID- 7585837
TI  - Block of impulse propagation at an abrupt tissue expansion: evaluation of the
      critical strand diameter in 2- and 3-dimensional computer models.
AB  - OBJECTIVE: Unidirectional conduction block in the heart can occur at a site where
      the impulse is transmitted from a small to a large tissue volume. The aim of this
      study was to evaluate the occurrence of conduction block in a 2-dimensional and 3
      dimensional computer model of cardiac tissue consisting of a narrow strand
      abruptly emerging into a large area. In this structure, the strand diameter
      critical for the occurrence of block, hc, was evaluated as a function of changes
      in the active and passive electrical properties of both the strand and the large
      medium. METHODS: The effects of changes in the following parameters on hc were
      analysed: (1) maximum sodium conductance (gNamax), (2) longitudinal (Rx) and
      transverse (Ry) intracellular resistivities, and (3) inhomogeneities in gNamax
      and Rx and Ry between the strand and the large area. Three ionic models for
      cardiac excitation described by Beeler-Reuter, Ebihara-Johnson, and Luo-Rudy
      ionic current kinetics were compared. RESULTS: In the 2-dimensional simulations,
      hc was 175 microns in Ebihara-Johnson and Beeler-Reuter models and 200 microns in
      the Luo-Rudy model. At the critical strand diameter, the site of conduction block
      was located beyond the transition, i.e. a small circular area was activated in
      the large medium, whereas with narrower strands conduction block occurred within
      the strands. The decrease of gNamax resulted in a large increase of hc. This
      increase was mainly due to the change of gNamax in the large area, while hc was
      almost independent of gNamax in the strand. Changing Rx had no effect on hc,
      whereas the increase of Ry decreased hc and reversed conduction block.
      Inhomogeneous changes of Rx and Ry in the strand versus the large medium had
      opposite effects on hc. When the resistivities of the strand alone were
      increased, hc also increased. In contrast, the increase of the resistivities in
      the large area reduced hc. In the 3-dimensional model, hc was 2.7 times larger
      than the corresponding 2-dimensional values at the various levels of gNamax and
      resistivity. CONCLUSIONS: (1) At physiological values for active and passive
      electrical properties, hc in the 2D simulations is close to 200 microns in all
      three ionic models. In the 3-dimensional simulations, hc is 2.7 larger than in
      the 2-dimensional models. (2) The excitable properties of the large area but not
      of the strand modify hc. The decrease of intercellular coupling in the large
      medium facilitates impulse conduction and reduces hc, while the same change in
      the strand increases hc. (3) Occurrence of conduction block at an abrupt
      geometrical transition can be explained by both the impedance mismatch at the
      transition site and the critical curvature beyond the transition.

PMID- 7585835
TI  - Inhibition of nitric oxide synthesis protects the isolated working rabbit heart
      from ischaemia-reperfusion injury.
AB  - OBJECTIVES: Nitric oxide (NO) exerts both protective and detrimental actions in a
      variety of biological systems. During acute reperfusion following myocardial
      ischaemia, a rapid overproduction of free radicals, including NO, may occur. We
      investigated the effects of the NO synthase inhibitors NG-nitro-L-arginine methyl
      ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), and the substrate for NO
      synthesis, L-arginine, on heart function during ischaemia and reperfusion injury.
      METHODS: Spontaneously beating, isolated working rabbit hearts, perfused with
      modified Krebs-Henseleit buffer containing 1.2 mM palmitate bound to 3% bovine
      serum albumin, were subjected to 15 min of aerobic perfusion followed by 35 min
      of global, no-flow ischaemia and 30 min of aerobic reperfusion. RESULTS:
      Throughout the reperfusion period there was a marked impairment in the recovery
      of mechanical function, measured as the product of heart rate x peak systolic
      pressure (rate-pressure product). Addition of L-NAME (3 microM) prior to the
      onset of ischaemia, but not at reperfusion, caused an immediate and significant
      increase in the recovery of mechanical function throughout the reperfusion
      period. The protective action of L-NAME was abolished by L- (but not D-) arginine
      (100 microM). L-NAME did not cause ischaemia as it did not alter glycogen or
      lactate content of aerobically perfused hearts. Furthermore, it did not prevent
      glycogen loss or lactate accumulation during 35 min of ischaemia, suggesting that
      the effects of L-NAME were not due to metabolic alterations during ischaemia
      itself. L-NMMA (30 microM) added prior to ischaemia, but not at reperfusion, also
      had a protective effect which was seen later in the reperfusion period. Addition
      of L- (but not D-) arginine (100 microM) prior to the onset of ischaemia resulted
      in an improved recovery of mechanical function only at 15 min of reperfusion.
      CONCLUSIONS: These results suggest that: (1) the recovery of mechanical function
      of hearts subjected to ischaemia-reperfusion injury can be improved by modulation
      of myocardial NO synthesis, (2) inhibition of NO synthesis (with L-NAME or L
      NMMA) may offer prolonged protection whereas its stimulation (with L-arginine)
      provides only brief protection, and (3) the reasons for the pharmacological
      effectiveness of these divergent strategies may be due to the formation of
      peroxynitrite from NO and superoxide anion during reperfusion.

PMID- 7585838
TI  - Regulation of glibenclamide-sensitive K+ current by nucleotide phosphates in
      isolated rabbit pulmonary myocytes.
AB  - OBJECTIVE: Although the existence of ATP-sensitive K+ (KATP) channels in vascular
      muscle is widely accepted, there appears to be little consensus as to what the
      primary regulator of these channels is under physiological or pathophysiological
      conditions. Recent evidence has suggested that nucleotide diphosphates (NDPs) may
      play a more important role than ATP. However, since the properties of vascular
      KATP channels are quite diverse, and the effects of these nucleotides are poorly
      understood, the aim of this study was to test the hypothesis that intracellular
      ATP can regulate whole-cell KATP current (IK,ATP) in the absence of NDPs.
      METHODS: Single cells were isolated from rabbit main pulmonary artery by
      enzymatic treatment with papain. Whole-cell patch clamp experiments were
      performed in cells dialysed with different nucleotides. The effect of the KATP
      channel activator, levcromakalim (10 microM), was investigated at a holding
      potential of -60 mV. The contribution of IK,ATP to the holding current was
      defined as the current which was blocked by glibenclamide following washout of
      levcromakalim. RESULTS: Lowering the intracellular ATP concentration ([ATP]i)
      from 1 to 0.1 mM, in the presence or absence of GTP, enhanced the levcromakalim
      induced current (Ilev) by approximately 2.5 fold and increased a glibenclamide
      sensitive background K+ current (Iglib). However, Iglib was larger with GTP and
      the total glibenclamide-sensitive current (Ilev+Iglib) increased with time.
      Significant activation of Iglib failed to occur when the pipette contained no
      nucleotides and the responses to levcromakalim were generally much smaller than
      seen with ATP. GDP (0.5 mM), in the absence of pipette ATP, activated a large
      background K+ current which had similar properties to Ilev. Consistent with this
      was the observation that Ilev became substantially reduced in the presence of
      GDP, presumably because a significant amount of IK,ATP was already activated.
      CONCLUSIONS: The response to levcromakalim in isolated cells from pulmonary
      artery was, as expected for an agent activating KATP channels, modulated by
      changes in the pipette [ATP]. This effect was not dependent on the presence of
      other pipette nucleotides, although the possibility cannot be excluded that
      metabolites from the cellular breakdown of ATP are essential for normal channel
      regulation. GDP could also activate IK,ATP under conditions where the channel is
      probably in a low phosphorylation state. The time-dependent effects of GTP
      require further work to determine the precise mechanism, but may suggest that GTP
      and/or G-proteins are involved in the regulation of KATP channels.

PMID- 7585839
TI  - Effects of nitric oxide synthase inhibition on the muscle blood flow response to
      exercise in rats with heart failure.
AB  - OBJECTIVE: The aim of this study was to investigate whether the role of nitric
      oxide (NO) in regulating blood flow (BF) to working skeletal muscle is impaired
      in chronic heart failure (CHF). METHODS: The effect of NG-nitro-L-arginine methyl
      ester (L-NAME), an inhibitor of NO synthesis, was studied in conscious rats with
      and without CHF due to myocardial infarction (MI). BF to the hindquarter
      musculature was measured with radiolabelled microspheres during exercise after 4
      min of treadmill running (10% grade, 20 m/min) before and after L-NAME (20 mg/kg
      i.a.) administration. RESULTS: Before L-NAME administration, BF measured in the
      total hindquarter musculature was less (P < 0.05) during exercise in rats with a
      large MI (MI size; 44 +/- 2% of the left ventricular endocardial circumference; n
      = 8) when compared with sham-operated rats (SHAM; n = 10) and rats with a small
      MI (MI size; 25 +/- 4%; n = 5). The BF measured during exercise following L-NAME
      administration was similar between the 3 groups. Of the 28 individual hindquarter
      muscles, BF was reduced in 23 and 19 muscles following the administration of L
      NAME for the SHAM rats and rats with a small MI, respectively. In comparison, BF
      was reduced to only 4 of 28 muscles in rats with a large MI. CONCLUSIONS: These
      results suggest that the contribution of the NO pathway to the hyperaemic BF
      responses found in the hindquarter muscles during exercise could be attenuated in
      rats with CHF. This attenuation of the NO pathway may be associated with the
      impairment of skeletal muscle BF distribution during exercise in CHF.

PMID- 7585840
TI  - Multicenter, phase IV evaluation of intravenous ciprofloxacin as initial therapy
      in patients with lower respiratory tract, urinary tract, and skin/skin structure
      infections.
AB  - A prospective, open-label, multicenter, Phase IV study of the efficacy and safety
      of intravenous (IV) ciprofloxacin (400 mg by 60-minute infusion every 12 hours)
      in the treatment of lower respiratory tract infections (LRTIs), urinary tract
      infections (UTIs), and skin/skin structure infections (SSSIs) in hospitalized
      patients was conducted in 1991. After a minimum of 3 days of IV therapy, patients
      could be switched to oral therapy with any antimicrobial. Of 360 patients who
      were valid for investigator assessment of clinical outcome at the end of IV
      therapy, a favorable outcome (cure and improvement in infection) was reported in
      337 (94%) patients and failure was reported in 23 (6%) patients. Of 330 patients
      valid for investigation assessment of clinical outcome at the end of all therapy
      (IV treatment alone or IV treatment followed by an oral antimicrobial), a
      favorable outcome was noted in 311 (94%) patients, and failure occurred in 19
      (6%) patients. Adverse events were noted in 72 (9%) of 782 patients and led to
      premature discontinuation of IV therapy in 23 (3%) patients. IV ciprofloxacin
      appears to be effective and safe in the management of mild-to-moderate LRTI and
      SSSI and mild, moderate, or severe UTI in hospitalized patients.

PMID- 7585842
TI  - Effect of low-dose simvastatin on cholesterol levels, oxidative susceptibility,
      and antioxidant levels of low-density lipoproteins in patients with
      hypercholesterolemia: a pilot study.
AB  - In this pilot study, 12 patients (6 men, 6 postmenopausal women) with
      hypercholesterolemia were treated with low-dose (5 mg/d) simvastatin, a 3-hydroxy
      3-methylglutaryl coenzyme A reductase inhibitor, for 4 weeks. Low-density
      lipoprotein (LDL) samples were isolated at the beginning (week 0) and at the end
      (week 4) of the treatment regimen. Simvastatin caused significant decreases of
      total cholesterol (-18.1%), LDL cholesterol (-27.6%), and apolipoprotein B (
      21.8%), and significantly reduced total cholesterol, free cholesterol,
      cholesterol esters, phospholipids, and protein in LDL without significantly
      changing the component ratios and fatty acid levels of LDL. However, simvastatin
      therapy had no major effects on either antioxidant levels in LDL or the oxidative
      susceptibility of LDL. We conclude that low-dose simvastatin significantly
      reduces LDL cholesterol levels without increasing the oxidative susceptibility of
      LDL or decreasing the antioxidant levels of LDL, and thus may reduce the risk of
      coronary artery disease.

PMID- 7585841
TI  - ICI 204,636, a novel, atypical antipsychotic: early indication of safety and
      efficacy in patients with chronic and subchronic schizophrenia.
AB  - We evaluated the effects of ICI 204,636 in 12 hospitalized patients with
      schizophrenia in a double-blind, placebo-controlled, parallel-group, rising-dose
      study. Patients met the Diagnostic and Statistical Manual of Mental Disorders,
      Third Edition, Revised criteria for chronic or subchronic schizophrenia and had a
      total score > or = 30 on the 18-item Brief Psychiatric Rating Scale (BPRS) and a
      score > or = 3 on the Clinical Global Impression (CGI) Severity of Illness item.
      Patients received 21 days of double-blind treatment with increasing doses of ICI
      204,636 (25 to 250 mg/d) or placebo. Efficacy was assessed using the BPRS and
      CGI. Response to treatment was defined as a > or = 30% decrease in the BPRS total
      score from baseline. Extrapyramidal symptoms and abnormal involuntary movements
      were assessed using the Simpson Scale and Abnormal Involuntary Movement Scale.
      Changes from baseline in the BPRS and CGI were significantly greater at end point
      for patients who received ICI 204,636 versus placebo (BPRS, -20.9 vs -4.8; CGI, 
      2.9 vs -1.0; P < 0.05, analysis of covariance; P < or = 0.06, Wilcoxon rank sum
      test). All patients in the ICI 204,636 group responded to treatment (P < 0.10)
      versus only two patients in the placebo group. Mild somnolence occurred in 50% of
      ICI 204,636-treated patients. No treatment-emergent extrapyramidal symptoms or
      dystonic reactions were observed. ICI 204,636 showed efficacy in the positive and
      negative symptoms of schizophrenia and was well tolerated.

PMID- 7585843
TI  - Efficacy and safety of twice-daily augmented betamethasone dipropionate lotion
      versus clobetasol propionate solution in patients with moderate-to-severe scalp
      psoriasis.
AB  - This 2-week, randomized, multicenter, investigator-blinded, parallel-group study
      was conducted to compare the efficacy and safety of augmented betamethasone
      dipropionate 0.05% lotion and clobetasol propionate 0.05% solution in the
      treatment of moderate-to-severe scalp psoriasis among 197 (193 assessable)
      healthy adult patients with at least 20% scalp-surface involvement. The patients
      received one of two treatments applied twice a day for 2 weeks. Signs and
      symptoms were evaluated at baseline, after 3 days (day 4), and after weeks 1 (day
      8) and 2 (day 15) of treatment. As early as 3 days after treatment, scaling and
      induration were improved significantly faster by betamethasone dipropionate than
      by clobetasol propionate. Both treatments also reduced erythema and pruritus.
      Patients receiving betamethasone dipropionate had a significantly greater mean
      percent improvement in total sign/symptom scores (P < or = 0.015) at all visits
      and better mean global clinical response scores at the early visits (days 4 and
      8) (P < or = 0.017). At the end of the study, only mild disease was present in
      both groups. Adverse events were reported by 34.0% and 36.4% of patients
      receiving betamethasone dipropionate and clobetasol propionate, respectively. All
      events were transient, most were mild and local, and no discontinuations
      resulted. The effects of treatment on the hypothalamic-pituitary-adrenal axis
      were not measured. In conclusion, augmented betamethasone dipropionate lotion and
      clobetasol propionate solution were equally effective, but betamethasone
      dipropionate lotion provided a faster onset of relief for scaling and induration,
      which may enhance patient compliance and patient satisfaction with treatment.

PMID- 7585844
TI  - Efficacy and safety of risperidone in the long-term treatment of patients with
      schizophrenia.
AB  - The long-term efficacy and safety of risperidone were evaluated in patients with
      chronic schizophrenia in an open-label study. Thirty-two patients received
      risperidone for 1 year and 19 of the 32 received risperidone for 2 years. The
      mean dose of risperidone was 9.4 mg/d in the 1-year follow-up. At the end of 1
      and 2 years, improvements were found in total scores on the Positive and Negative
      Syndrome Scale (PANSS), on four PANSS factors (positive, negative, excited, and
      cognitive), and the Clinical Global Impression scale. Severity of extrapyramidal
      symptoms (based on scores on the Extrapyramidal Symptom Rating Scale) was also
      reduced. Clinical improvement (defined as a 20% or more reduction in total PANSS
      scores) was shown by 54% of the patients at end point. Social functioning (as
      assessed by using the modified Strauss/Carpenter scale) was significantly
      improved after 2 years. Number of days spent in hospitals was significantly
      reduced during the 2 years of treatment, and the number of days in treatment
      (group) homes significantly increased. It is concluded that treatment with
      risperidone for 1 and 2 years is associated with significant reductions in
      symptoms of schizophrenia, improved social functioning, and reduction in days
      spent in the hospital.

PMID- 7585845
TI  - Single daily dose of cefodizime in patients with community-acquired pneumonia: an
      open-label, controlled, randomized study. The Italian Multicentre Community
      Acquired Pneumonia Group.
AB  - The objective of this study was to compare the clinical and bacteriologic
      efficacy and safety of cefodizime 1 g intramuscularly (IM) once daily (group A)
      versus cefodizime 1 g IM twice daily (group B) and versus ceftriaxone 1 g IM once
      daily (group C) in patients with community-acquired pneumonia. A total of 298
      patients, affected by bronchopneumonia or pneumonia with known or suspected
      bacterial cause, new focal signs on examination of chest, and radiographic
      evidence of a recent infiltrate, were randomized in three comparable groups. The
      infection was rated as mild, moderate, or severe. A total of 283 patients were
      assessable for efficacy: 95 in group A, 94 in group B, and 94 in group C. Mean
      (+/- SD) duration of treatment was 5.96 +/- 1.39 days in group A, 6.24 +/- 1.57
      days in group B, and 6.66 +/- 1.95 days in group C. Symptoms such as purulent
      sputum, cough, and dyspnea improved significantly after treatment in all groups;
      temperature normalized by about day 3. Clinical efficacy was rated good in 94.74%
      of patients in group A, in 92.55% in group B, and in 87.23% in group C. Positive
      bacteriologic cultures were obtained before treatment from 144 patients:
      bacteriologic responses were rated good in 98.11%, 98.08%, and 92.80% in groups
      A, B, and C, respectively. No significant differences were found between the
      three treatment groups for any measures of clinical efficacy. No serious adverse
      event occurred in any of the groups. We conclude that cefodizime 1 g IM once
      daily is an effective dosing regimen in the treatment of patients with community
      acquired pneumonia.

PMID- 7585846
TI  - Ganciclovir absolute bioavailability and steady-state pharmacokinetics after oral
      administration of two 3000-mg/d dosing regimens in human immunodeficiency virus-
      and cytomegalovirus-seropositive patients.
AB  - Oral ganciclovir has recently been approved for use in long-term maintenance
      therapy in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised
      patients. Although oral ganciclovir at a dose of 3,000 mg/d is moderately less
      effective than intravenous (i.v.) ganciclovir maintenance therapy (5 mg/kg as a 1
      hour i.v. infusion every 24 hours), convenience and practicality make oral
      maintenance therapy desirable. Two dosing regimens--1,000 mg three times daily
      (TID) and 500 mg every 3 hours (six times daily)--have been shown to be
      efficacious. Eighteen human immunodeficiency virus- and CMV-seropositive patients
      participated in a three-way, open-label, crossover study to evaluate the steady
      state pharmacokinetics and absolute bioavailability of the two oral regimens
      compared with the i.v. regimen. Sixteen patients completed the study and received
      ganciclovir as a single 5-mg/kg i.v. infusion over 1 hour, 500 mg orally every 3
      hours while awake (six times daily) for 3 days, and 1,000 mg TID orally for 3
      days. Blood samples were obtained over a 24-hour period after the single i.v.
      dose and on day 3 of the oral dosing regimens. Mean peak serum concentrations
      were 8.27, 1.02, and 1.18 micrograms/mL for the i.v. and oral regimens,
      respectively. Twenty-four-hour area under the curve (AUC) for the oral regimens-
      500 mg every 3 hours and 1,000 mg TID--were 15.9 and 15.4 micrograms.h/mL,
      respectively, as compared with a total AUC of 22.1 micrograms.h/mL for the single
      i.v. dose. The absolute bioavailabilities for the two oral regimens were 8.84%
      and 8.53%, respectively. The extent of ganciclovir absorption, peak
      concentrations, and average concentration at steady state were not statistically
      different between the two oral regimens. The peak-to-trough concentration ratio
      (Cmax:Cmin) was greater for the 1,000-mg TID regimen than for the regimen of 500
      mg every 3 hours (5.35 vs 3.81 [P < 0.01]). Both oral regimens resulted in
      concentrations in the range of the concentration that inhibits 50% of most human
      CMV isolates. Because both oral regimens provide equivalent absorption, the 1,000
      mg TID regimen may be preferred for the convenience and potentially greater
      compliance associated with fewer daily doses.

PMID- 7585847
TI  - Comparison of gastric mucosal surface pH response times after intravenous
      administration of histamine2-receptor antagonists.
AB  - Gastric mucosal surface pH was measured endoscopically in patients with peptic
      ulcer, erosive gastritis, or nonulcer dyspepsia following intravenous
      administration of either 200-mg cimetidine, 50-mg ranitidine, or 40-mg
      famotidine. The mean baseline pH in the three treatment groups before drug
      administration ranged from 0.85 to 0.99, with no significant difference between
      groups. Following treatment with cimetidine, ranitidine, and famotidine, the mean
      response times for the mucosal surface pH values to increase to 3.5 were 10.1 +/-
      5.9 minutes, 11.2 +/- 6.8 minutes, and 17.3 +/- 6.7 minutes, respectively. The
      corresponding response times to reach pH levels of 6.0 were 16.0 +/- 9.4 minutes,
      17.0 +/- 5.4 minutes, and 31.2 +/- 21.7 minutes, respectively. The response times
      to pH levels of 3.5 and 6.0 were significantly faster in patients who received
      cimetidine compared with patients who received famotidine (P = 0.0088 to pH 3.5
      and P = 0.046 to pH 6.0). The differences between cimetidine and ranitidine were
      not significant. These findings suggest that at recommended clinical doses,
      intravenous cimetidine provides rapid elevation of the gastric mucosal surface pH
      compared with other histamine2-receptor antagonists. This finding may be
      particularly relevant in the emergency care of patients with severe peptic ulcer
      disease (eg, patients with gastrointestinal hemorrhage).

PMID- 7585848
TI  - Lansoprazole: an alternative method of administration of a capsule dosage
      formulation.
AB  - A single-dose, open-label, randomized, fasting, two-period, crossover
      bioavailability study was conducted in 24 healthy adult men to assess an
      alternative method of administration of lansoprazole capsules. Half of the
      subjects received regimen A (contents from a 30-mg capsule placed in a
      tablespoonful of applesauce), and the other half received regimen B (an intact 30
      mg capsule) during period 1 of the crossover study. The regimens were reversed
      during the second period 1 week later. Blood samples were obtained over 12 hours
      and pharmacokinetic parameters were determined. Mean time elapsed to peak
      concentration (Tmax) was less than 2 hours for each regimen. The ratio (regimen
      A:regimen B) of peak concentration (Cmax) means and area under the curve (AUC)0
      infinity means were 0.889 and 0.944, respectively. (AUC0-infinity is the sum of
      AUC0-t and AUCt-infinity, where AUC0-t is the area under the plasma concentration
      time curve from time 0 to the time of the last measurable or nonzero
      concentration as computed by using the trapezoidal rule, and AUCt-infinity is
      computed as the last nonzero concentration divided by the terminal phase rate
      constant.) No statistically significant differences (P < or = 0.05) in Tmax,
      Cmax, and AUC0-infinity were detected between regimens. These data indicate
      similar bioavailabilities between the two regimens. Lansoprazole granules
      contained in a standard capsule dosage formulation may be removed and placed
      directly into applesauce and administered to appropriate patients.

PMID- 7585849
TI  - Effect of omeprazole on changes in gastric and upper small intestine pH levels in
      patients with chronic pancreatitis.
AB  - Gastric and upper small intestine pH levels were measured continuously over 24
      hours in patients with chronic pancreatitis, and values obtained before and after
      the administration of omeprazole were compared. Additionally, omeprazole was
      administered for 2 weeks and the fecal excretion of fat was compared before and
      after drug therapy. Postprandial gastric pH levels, initially 2.9 to 3.2,
      increased by 1.6 to 2.1 after treatment. Postprandial upper small intestine pH
      levels, initially 5.1 to 5.5, increased by 0.7 to 1.0. The lowest pH value of the
      upper small intestine was 2.2 to 2.4 postprandially; this was increased by > 1.0
      after omeprazole, and the amplitude of pH variation was reduced. The cumulative
      proportions of intraintestinal pH strata of < or = 3, < or = 4, or < or = 5, and
      higher, initially being 16.4% to 17.1%, 27.4% to 31.7%, and 52.6% to 57.8%,
      respectively, were remarkably improved after drug treatment. Gastric pH and upper
      small intestine pH levels showed a positive correlation; an increase in gastric
      pH levels by 2 corresponded to an increase in small intestine pH levels by 1.
      After omeprazole administration, mean fecal excretion of fat was decreased to 4.1
      +/- 2.6 g/d (range, 1.1 to 9.8 g/d) from 6.5 +/- 3.9 g/d (range, 1.6 to 13.5
      g/d). Decreases in excretion of fat averaged 3.4 g/d (range, 2.2 to 4.5 g/d) in
      patients with steatorrhea. It was concluded that steatorrhea due to chronic
      pancreatitis can be improved to some extent by improving upper small intestine pH
      levels following the elevation of gastric pH levels after administration of
      omeprazole.

PMID- 7585850
TI  - Effect of 24 weeks of treatment with epalrestat, an aldose reductase inhibitor,
      on peripheral neuropathy in patients with non-insulin-dependent diabetes
      mellitus.
AB  - The effects of treatment with epalrestat, an aldose reductase inhibitor, on
      peripheral neuropathy were studied in 45 patients with non-insulin-dependent
      diabetes mellitus (NIDDM). Epalrestat 150 mg three times daily was given for 24
      weeks. Subjective symptoms, such as spontaneous pain in the lower extremities and
      numbness and hypoesthesia of the extremities or trunk, were significantly (P <
      0.001) relieved after 12 and 24 weeks of epalrestat treatment. Vibratory
      perception thresholds, as measured by using a tuning fork (C-128) and a
      vibrometer, were improved after 24 weeks of treatment. Furthermore, there were no
      adverse effects on glucose or lipid metabolism during treatment. These results
      suggest that long-term (24-week) epalrestat therapy can be used effectively to
      treat peripheral neuropathy in NIDDM patients without affecting glucose or lipid
      metabolism.

PMID- 7585852
TI  - Comparison of intranasal triamcinolone acetonide with oral loratadine for the
      treatment of patients with seasonal allergic rhinitis.
AB  - This multicenter, double-blind, randomized, controlled, parallel-group study
      compared the safety and efficacy of intranasal triamcinolone acetonide with oral
      loratadine in relieving symptoms of ragweed-induced seasonal allergic rhinitis.
      Patients from community-based allergy practices with a history of at least two
      seasons of seasonal allergic rhinitis verified by a positive skin test received
      either once-daily treatment with intranasal triacinolone acetonide 220 micrograms
      plus 1 placebo capsule or oral loratadine 10 mg plus placebo nasal spray. Other
      medications for rhinitis were prohibited. Changes in rhinitis symptoms were
      assessed by using patient evaluations, physician global evaluations, and
      withdrawal rates. Efficacy was evaluated in 274 of 298 patients randomized to
      treatment (134 to triamcinolone acetonide and 140 to loratadine). Mean total
      nasal symptom scores for weeks 1, 2, 3, and 4 and the overall score showed
      greater improvement (P = 0.001) with triamcinolone acetonide than with
      loratadine. Improvement in all rhinitis symptoms was significantly greater with
      triamcinolone acetonide than with loratadine; there was a trend for greater
      improvement in ocular symptoms with triamcinolone acetonide. Physicians' global
      evaluations indicated triamcinolone acetonide provided moderate-to-complete
      relief in 78% of patients compared with 58% of loratadine-treated patients (P <
      or = 0.0001). Both treatments were well tolerated; headache was the most commonly
      reported adverse event in both groups. Intranasal triamcinolone acetonide was
      significantly more effective than oral loratadine in relieving the symptoms of
      seasonal allergic rhinitis.

PMID- 7585851
TI  - A multicenter, randomized, double-blind comparison of roxatidine with ranitidine
      in the treatment of patients with uncomplicated benign gastric ulcer disease. The
      Multicenter Roxatidine Cooperative Study Group.
AB  - Roxatidine (150 mg, 312 patients) was compared with ranitidine (300 mg, 308
      patients) in a randomized, double-blind, parallel-group, 6-week therapeutic study
      for the treatment of patients with uncomplicated, benign gastric ulcer disease.
      The study end points (verified by using endoscopy results) were fully healed
      ulcers at 4 or 6 weeks. The results of roxatidine therapy were comparable to
      those of ranitidine therapy: healing rates of 52% and 54% at week 4 and 77% and
      76% at week 6 were recorded for roxatidine and ranitidine, respectively. The
      drugs produced comparable reductions in ulcer diameters and decreases in
      abdominal pain. Adverse events associated with both roxatidine (27%) and
      ranitidine (28%) were headache, diarrhea, and dizziness; rash was associated in 6
      of 8 cases and in only 1 case with roxatidine. In this trial, roxatidine 150 mg
      once daily was as efficacious and safe as ranitidine 300 mg once daily for
      treatment of patients with uncomplicated, benign gastric ulcer disease.

PMID- 7585853
TI  - Comparison of enoxacin versus trimethoprim-sulfamethoxazole in the treatment of
      patients with complicated urinary tract infection.
AB  - Given the prevalence of complicated urinary tract infection (UTI) and the
      resistance patterns of common uropathogens, antimicrobial therapy for complicated
      UTI must be carefully selected. For patients with complicated UTI who can be
      treated with oral medication, the quinolones or trimethoprim-sulfamethoxazole
      (TMP-SMX) are reasonable treatment choices. Enoxacin and TMP-SMX were compared
      for efficacy, safety, and bacteriologic response in this study. A total of 260
      patients with complicated UTI were enrolled in a multicenter, open-label,
      randomized study and received enoxacin or TMP-SMX. Short-term assessments 5 to 9
      days posttherapy and long-term assessments 4 to 6 weeks posttherapy included
      physical and clinical evaluations, laboratory testing, urine cultures, and
      susceptibility testing. Although enoxacin and TMP-SMX demonstrated comparable
      short-term efficacy rates, enoxacin exerted a potent, long-term bacteriologic
      response, particularly against Escherichia coli. Enoxacin therapy achieved a
      94.7% long-term eradication rate against E coli compared with a 76.0% eradication
      rate against this pathogen with TMP-SMX. Most adverse events were mild, and a
      comparable incidence (approximately 17%) occurred in both treatment groups. These
      data indicate that enoxacin is an excellent addition to the armamentarium of
      agents commonly used in the treatment of patients with complicated UTI.

PMID- 7585855
TI  - Survey results from academic health center intensive care units: considerations
      for departments of pharmacy.
AB  - Using survey data collected from 24 University Hospital Consortium member
      institutions, this paper examines the role of pharmacy in quality-improvement and
      cost-reduction initiatives in academic health center intensive care units. The
      results illustrate that most institutions are not taking full advantage of the
      services a clinical pharmacy has to offer, and that using these services could
      improve the quality and cost-efficiency of care.

PMID- 7585856
TI  - Effects of Medicaid drug utilization review intervention letters.
AB  - The state of Texas Drug Utilization Review (DUR) Board, composed of six
      physicians and six pharmacists, meets quarterly to determine criteria for
      implementing retrospective DUR. The board agreed to send intervention letters to
      physicians concurrently prescribing: (1) two histamine2 (H2)-antagonists (H2As)
      or (2) either any H2A or omeprazole with sucralfate. To measure the effect of
      these intervention letters, approximately half of these physicians were randomly
      chosen to receive a letter while the others served as a control group and did not
      receive letters. This project focused on the H2A or omeprazole with sucralfate
      intervention letters in a two-step process. Data on concurrent therapy involving
      two H2As were analyzed separately and these results are not included in this
      report. Objective one was to examine feedback from the physicians who received
      the letters, and objective two was to review and compare patient profiles 6
      months after the letters were sent. Analysis of Medicaid prescription claims
      indicated that 190 physicians had concurrently prescribed either an H2A or
      omeprazole with sucralfate for 222 patients. Ninety-seven physicians (from 117
      identified patient profiles) were selected to receive an intervention letter with
      their patient's profile or profiles, a response form, and a stamped envelope
      addressed to the Texas Department of Human Services. A 67.5% response rate was
      obtained. Of these responses, 49.4% agreed with the letter and 29.1% disagreed
      with the letter. The remaining indicated responses such as "not my patient," they
      were no longer seeing the patient, or that they did not prescribe the medication
      in question. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585854
TI  - Triamcinolone acetonide aqueous nasal spray for the treatment of patients with
      perennial allergic rhinitis: a multicenter, randomized, double-blind, placebo
      controlled study.
AB  - In this multicenter, randomized, double-blind, placebo-controlled study, 178
      patients with symptoms of perennial allergic rhinitis (PAR) were treated with
      either triamcinolone acetonide (TAA) Aqueous nasal spray (220 micrograms once
      daily) or placebo for 4 weeks. Symptoms of PAR (nasal stuffiness, nasal
      discharge, sneezing, nasal index, and nasal itching) were evaluated throughout
      the treatment period through the use of patient diaries. In addition, both
      patients and physicians completed independent global evaluations of treatment
      efficacy at the conclusion of the study. TAA Aqueous provided clinically and
      statistically (P < or = 0.05) greater improvements in nasal stuffiness, sneezing,
      nasal index, and nasal itching over the 4-week study period than did placebo.
      Significant improvements in sneezing (P = 0.022) were observed as early as the
      first day (within 12 to 16 hours based on treatment in the morning and assessment
      of symptoms at bedtime), and in the nasal index (P = 0.009) by the third day
      after treatment with TAA Aqueous. Patients' and physicians' global evaluations of
      overall efficacy were concordant: 65% of patients rated their nasal symptoms
      greatly or somewhat improved with TAA Aqueous compared with 48% in the placebo
      group; physicians rated 66% of patients as having greatly or somewhat improved
      symptoms with the study drug compared with 48% of patients who received placebo.
      Adverse events were mild and the incidences were comparable for both groups; no
      significant changes in vital signs or clinical laboratory parameters were
      observed. This study demonstrated that TAA Aqueous administered once daily was
      well tolerated and provided relief of PAR symptoms in adults and adolescents.

PMID- 7585858
TI  - A comparative evaluation of oral contraceptive use and associated compliance
      issues in a rural population.
AB  - One hundred thirty-three patients were enrolled in a study designed to evaluate
      and compare oral contraceptive use in three rural communities. The patients
      averaged 31 years old (range, 13 to 49 years); 92% were white, 4.5% Hispanic, and
      3% Native American. Genora, Ortho-Novum, and Triphasil were the most frequently
      prescribed oral contraceptives. Triphasic oral contraceptives accounted for one
      third (n = 64) of 203 prescriptions, and conventional monophasic preparations
      accounted for two thirds. Twenty percent (n = 26) of the patients studied were
      non-compliant. The most frequent causes of noncompliance cited were cost and
      inconvenience. However, generic alternatives were requested in only 43% of the
      cases for which generic equivalents were available. Less-expensive alternatives
      (eg, generic products, medroxyprogesterone acetate injection) should be advocated
      to deter patient noncompliance because of cost issues. Drug interactions and
      adverse effects were not reported in our patient population and thus did not
      contribute to noncompliance.

PMID- 7585860
TI  - Use of anesthesia selection in controlling surgery costs in an HMO hospital.
AB  - The cost of induction and maintenance of anesthesia is analyzed in this article
      from the perspective of a health maintenance organization's (HMO) chief financial
      officer. While earlier economic studies tended to focus on the raw cost of
      anesthesia drugs, our model also includes the cost of the clinical labor involved
      in administering the drug as well as the fixed costs associated with the
      facility. Such a model is consistent with the goal of an HMO, which is to provide
      high-quality health care services to its membership while containing costs. Our
      model disaggregated the costs associated with anesthesia into cost centers. The
      costs associated with two anesthesia regimens, propofol and
      thiopental/isoflurane, were calculated and analyzed via cost-minimization
      methods. Our data were acquired from a prospective economic trial conducted in
      university, community, and HMO hospitals. Because institutional pricing policies
      differ greatly, only the findings at the HMO hospital are presented in this
      report. Our results suggest that intra-abdominal surgical procedures with a
      duration of less than 4 hours that use propofol for induction and maintenance of
      anesthesia reduce the total cost of surgery by $202.71, compared with the costs
      of using thiopental/isoflurane. Sensitivity analysis maintains the robustness of
      the conclusions with regard to all major parameters.

PMID- 7585861
TI  - Cost-effectiveness analysis of lipid-modifying therapy in Canada: comparison of
      HMG-CoA reductase inhibitors in the primary prevention of coronary heart disease.

PMID- 7585857
TI  - Pharmacist-managed intravenous to oral step-down program.
AB  - In an effort to provide cost-effective pharmaceutical care at a 650-bed community
      hospital, a pharmacist-managed intravenous to oral step-down program was
      developed and implemented. As part of this program, satellite pharmacists review
      daily the charts of patients receiving 1 or more of 10 targeted drugs given
      intravenously. Based on a predetermined set of criteria and their clinical
      judgment, pharmacists recommend that physicians switch to the oral formulation of
      the targeted drugs if appropriate. This program has been in place for 7 months,
      during which time 223 recommendations were made. Of these recommendations, 190
      were accepted and implemented, resulting in a cost savings of $21,596.00. When
      annualized, the expected savings is $37,000.00 or nearly the salary of one full
      time pharmacist. This program has been well accepted by physicians and
      pharmacists. It appears to be having a positive impact on physician awareness of
      using oral medications when appropriate.

PMID- 7585859
TI  - Meta-analysis of three trials with quinapril in the treatment of mild-to-moderate
      hypertension in the Mexican population.
AB  - A meta-analysis was performed to examine the therapeutic effect of quinapril in
      the treatment of patients with mild-to-moderate hypertension. Data from three
      clinical trials conducted in Mexico and including a total of 426 patients were
      examined using a retrospective approach and statistical methods. The meta
      analysis proved that quinapril induces positive diastolic and systolic responses
      at all the doses studied, particularly at the 10-mg dose. At this dose, 94.1% of
      patients reduced their diastolic blood pressure (DBP) by 10 mm Hg or attained a
      DBP of < or = 90 mm Hg. Overall, quinapril reduced DBP by between 14.8 and 24.8
      mm Hg proportionally to the baseline DBP. Systolic blood pressure decreased 16 to
      35.7 mm Hg from baseline levels. We conclude that the meta-analysis allowed a
      clearer and more dependable handling of the results regarding effectiveness and
      optimum dose of quinapril.

PMID- 7585862
TI  - [Use of laboratory animals for toxicologic testing of drugs and chemicals].
AB  - For evaluation of the possible risk of drugs and chemicals for the human organism
      and its vital functions and to detect possible undesirable action on the
      environment, laboratory animals must be used. In toxicology as biomodels standard
      strains, as regards genetic and health aspects, mice, rats, rabbits, guinea pigs
      and dogs are used. The basis of standardization of conditions for keeping
      laboratory animals is as regards physical, chemical and biological aspects
      adherence to conditions of the adopted regulations of the Council of European
      Communities of Nov. 24, 1986. Council Directive 86/609/EEC, known in this country
      as the "Strasbourg convention". Part of the protection of laboratory animals used
      for experimental and other scientific purposes is also the adherence to the
      optimal number of animals as regards the area or cage where they are kept as well
      as the cubic measure of the space. Standardization of scientific results is
      promoted also by adherence to transport conditions of the animals, the time of
      acclimatization, quarantine. Knowledge of the basic biology of laboratory animals
      used should be obvious for experimental workers. All work on animals must be
      governed by valid laws and instructions which make work with animals possible. In
      the Czech Republic its is the act of the Czech National Council No. 246 issued in
      1992 for the protection of animals from maltreatment according to which work with
      animals can be carried out only by institutions with accreditation for the given
      work which moreover have an ethical commission which issues permission for work
      with animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7585866
TI  - [Clinical biochemistry and laboratory medicine in the 21st century].
AB  - The author gives an outline of the assumed development of clinical biochemical
      examinations in future decades based on the development during the past 40 years.
      The development of biochemical analyzers will probably mean more perfect
      robotization; the increase in capacity (number of tests performed per hour)
      probably will not result from more rapid individual analyses (the rate of 900
      tests/hour is probably optimal) but the capacity will be increased by doubling
      and trebling of critical elements (photometry or technique of measurements,
      pipetting etc.). Probably the volume of blood samples will not be reduces (to
      less than 1-2 microliters); however, amplification techniques will be used far
      more (as at present the polymerase chain reaction and others (for replication of
      cellular substances such as DNA). There will be a shift and greater use of "in
      vivo" techniques such as magnetic resonance spectroscopy and examinations using
      biosensors (because of the possibility and in particular expedience of examining
      some analytes continuously). The examined spectrum will be extended by further
      substances (in particular those with a short-term existence such as e.g.
      cytokines, selectins, adhesive molecules etc.; manifestations of circadian
      dynamics will be followed up much more e.g. in tumours, or chronopharmacokinetics
      of some drugs. A great development may be foreseen in the sphere of the use of
      computer technique for evaluation and communication of laboratory data and other
      data on the patient. For consultations global (or at least regional) computer
      networks will be much more widely used.

PMID- 7585867
TI  - [The human genome--chromosome 15].
AB  - The Prader-Willi syndrome (PWS) with Angelman's syndrome form a pair known above
      all due to problems of genetic imprinting and uniparental disomy. Both phenomena
      drew attention to the importance of control of expression of different alleles
      and their genetic origin. The causes of the two syndromes have not been
      elucidated unequivocally so far. In case of the PWS, at least, there is the
      possibility of a gene of the protein carrier of a small nuclear ribonucleic acid
      described as SNRPN. In case of Marfan's syndrome the responsible gene is the
      fibrillin gene (FNB1) with the locus on area 15q21. The mentioned gene
      participates probably also in diseases caused by a change of the vascular wall
      (aneurysm) and in prolapse of the mitral valves. On the 15th chromosome are
      several representatives of the family of genes of cytochrome P450 the products of
      which play a part in the metabolism of exogenous substances, incl. pharmaceutical
      ones. Their activity is part of the natural sensitivity or resistance to some
      chemical cancerogens. The postscriptis devoted to the assumed locus of dyslexia
      DLX1.

PMID- 7585864
TI  - [Effectiveness of conservative and surgical treatment of lumboischiadic
      syndrome].
AB  - BACKGROUND: Hitherto performed retrospective studies of conservative and surgical
      treatment of compressive radicular lumboischiadic syndrome did not provide a
      clear answer to the question which procedure cures the disease more effectively.
      The reason is that severe types of the disease treated by surgery were compared
      with therapeutic results of milder forms treated conservatively. The authors
      compared therefore the effectiveness of both therapeutic procedures in a
      prospective study with a random selection of patients as regards the therapeutic
      procedure. METHODS AND RESULTS: In two groups--first group comprising 100
      patients with the global syndrome and second group comprising 64 patients with
      the pure syndrome--the authors enlisted the patients by random selection for
      conservative or surgical treatment. Early results were assessed three months
      after treatment. Satisfactory results (cure) were achieved in 50% of the operated
      patients with the global syndrome, compared with 23.81% treated conservatively (p
      < 0.01), and improvement was recorded in 77.77% operated patients as compared
      with 58.69% conservatively treated patients (p < 0.05). In the group with the
      pure syndrome satisfactory results were achieved in 68.75% operated patients as
      compared with 21.87% conservatively treated patients (p < 0.001) and improvement
      in 81.25% patients as compared with 53.12% conservatively treated patients (p <
      0.01). CONCLUSIONS: The investigation proved a statistically significantly
      greater effectiveness of the surgical method of treatment of compressive
      radicular lumboischiadic syndrome as compared with conservative treatment. The
      second finding was that both methods have a relatively low effectiveness as
      regards, complete recovery. It is necessary to seek methods to increase the
      effectiveness of both therapeutic procedures, in particular clearly more
      effective surgical treatment.

PMID- 7585869
TI  - [The attitude of students regarding human dignity].
AB  - Contemporary secular thinking concerning human dignity is discussed. The opinions
      of a great majority of 523 students (Medical Faculty, Masaryk University, Brno)
      do not agree with the suggestion that suffering and terminal illness can rob the
      patient of his dignity (as, e.g. Motion of European Parliament for a resolution
      on care of the terminally ill in 1991 suggested). On the contrary the students
      claim that it is necessary to fight against such possible feeling of patients and
      that this feeling might be brought about by disrespectful behaviour of medical
      staff. The question "Which ethics for bioethics" is discussed as well. Because of
      the existing pluralism in the actual moral and philosophical situation the values
      and principles which are proposed in bioethics are extremely diversified. The
      necessity of a philosophical point of view that justifies respect for human life
      and its dignity in all its aspects is pointed out.

PMID- 7585870
TI  - [Underrated importance of Professor Josef Halla in the development of Czech
      medicine].

PMID- 7585863
TI  - [Catheterization therapy of thromboembolic arterial occlusions of the lower
      extremities].
AB  - Thromboembolic occlusions of peripheral arteries may threaten the vitality of
      extremities and sometimes patients life. Till recently the main therapeutic
      method was Fogarty surgical thromboembolectomy. A less invasive procedure is
      systemic (intravenous) and local (intraarterial) thrombolysis. All these method
      have, however, certain disadvantages. A new approach to the treatment for acute
      and subacute occlusions of peripheral arteries represents catheter
      thromboembolectomy, which involves the following: a) Aspiration of thromboembolic
      material--percutaneous thrombembolextraction (PTEE), b) Local infiltration
      thrombolysis where the catheter penetrates through the occlusion while
      simultaneously administering a fibrinolytic agent, c) PTA of residual stenosis in
      case of thrombotic occlusion. A combination of these methods of treatment for
      thromboembolic occlusions of peripheral arteries is very effective and enables to
      use a small amount of thrombolytic agent. The thrombosis and the underlying
      atherosclerotic stenosis are resolved during the same session.

PMID- 7585868
TI  - [How old are our drugs?].

PMID- 7585865
TI  - [Renal impairment in monoclonal gammapathies. Clinical study].
AB  - BACKGROUND: Renal involvement is an important and frequent complication in
      patient with monoclonal gammapathy (MG), especially in multiple myeloma (MM).
      Light chain proteinuria produces many renal manifestations, the most serious form
      is acute renal failure, which occurs in 5-10% of patients with MM. The frequency
      and form of renal involvement was determined in a group of patients with MG. The
      disturbances observed were correlated with the concentration and type of
      paraprotein in serum and urine. METHODS AND RESULTS: We investigated 82 patients,
      37 men and 45 women with an average age of 63.5 years. Apart from standard
      nephrologic tests the aminoaciduria/24 h and urine acidification capacity was
      determined. In some patients renal biopsy was performed. Proteinuria was observed
      in 66 cases (80.5%), in 54 of them of Bence-Jones type. Nephrotic syndrome
      developed in 4 patients, in all cases the renal amyloidosis was present. Renal
      insufficiency was diagnosed in 39 patients (47.5%), mostly in MM. In 14 cases was
      renal insufficiency reversible, in 14 remain stable and in 11 progressed during
      the course of disease. Irreversible progression developed in terminal phase of
      disease in most cases. Acute renal failure was observed in 6 patients, only in
      four of them further course of renal disease could be evaluated. In half of these
      4 patients the renal failure was reversible. CONCLUSIONS: Higher frequency of
      proteinuria and renal insufficiency was detected in patients with light chain
      paraprotein of lambda type, or biclonal kappa+lambda type. Aminoaciduria was
      diagnosed in 40% of patients, we did not observe complete Fanconi's syndrome.
      Incompleted form of renal tubular acidosis we diagnosed in 52% of cases without
      other signs of renal involvement.

PMID- 7585871
TI  - [The origin and early development of biological catalysts].
AB  - Biochemical processes are based on the catalytic activity of enzymes. Highly
      ordered stereometry of protein macromolecules perfectly adapted to fyziological
      function of enzymes is the result of a long evolution. Catalytic processes, e.g.
      inorganic catalysis on the surface of cosmic dust grains, or on the surface of
      clay particles on the Earth, occurred as early as during chemical evolution.
      Enzyme predecessors in prebiotic systems-probably, thermal polymers of amino
      acids (proteinoids)-were polyfunctional catalysts. Low-effective proteinoids have
      been replaced by the highly efficient and specific enzymes in the course of
      evolution; spatial and temporal co-ordination of the individual enzymes has
      developed instead of the proteinoid polyfunctionality. The comprehensive effect
      of the mixtures of hydrolytic enzymes in systemic enzyme therapy can be regarded
      as a as a sort of reflection of these evolutionary trends.

PMID- 7585872
TI  - [Proteolytic enzymes in cell physiology and pathophysiology].
AB  - Extracellular proteases (proteinases, endopeptidases) are usually synthesized as
      larger precursors containing a signal sequence in the N-terminal part of their
      molecule. The signal sequence contains a sequence composed of hydrophobic amino
      acids which facilitate the transport of the polypeptide through membranes of the
      secretory apparatus. Extracellular proteinases play an important role in
      reproduction and spreading of tumor cells and in tissue remodelling in addition
      to their function in digestion food proteins. Intracellular proteinases are
      mostly localized in the cytoplasm and in specialized organelles (lysosomes) but
      are present also in nuclei and in mitochondria. They degrade or modify cell
      proteins and are thus involved in protein turnover which is necessary for cell
      viability. Intracellular proteinases are important components of the cell defense
      system which protects the cell against the effect of different stress factors by
      removing damaged and nonfunctional proteins. They modify different proteins and
      are thus involved in virus reproduction because some proteins are synthesized as
      nonfunctional virus precursors. Intracellular proteinases also play a role in the
      cell cycle control and in cytodifferentiation. Rather complex proteolytic enzymes
      were found even in very primitive organisms (archebacteria).

PMID- 7585874
TI  - Pharmacological effects of oral enzyme combinations.
AB  - Combinations of hydrolytic enzymes have been used for therapy of variety of
      diseases for a long time, their pharmacology, however, is being recognized only
      in the course of last decades. In the article, the following pharmacological
      effects of combinations of oral hydrolytic enzymes are reviewed: fibrinolytic,
      hemorheologic, anti-edematous, anti-inflammatory, activation of macrophages and
      NK cells, modulation of adhesion molecules, cytokines and immune complexes.
      Pharmacological effects are classified on four levels: biochemical,
      physiological, medical, and immunological. A spectrum of indications of enzyme
      therapy is inferred from the pharmacological effects: inflammations,
      traumatological events, surgical interventions, autoimmune and immune complex
      diseases, rheumatological diseases, viral infections and malignant tumors.

PMID- 7585873
TI  - [Systemic enzyme therapy: problems of resorption of enzyme macromolecules].
AB  - Systemic enzyme therapy represents a special therapeutic approach consisting in
      the oral application of high doses of hydrolytic animal and plant enzyme
      combinations. The originally empirical method was by detailed experimental
      analyses and successful clinical studies transformed into a widely appreciated
      therapeutic method of various pathologic processes. In spite of this fact
      systemic enzyme therapy has been repeatedly questioned by referring to an almost
      hundred year old dogma claiming the unabsorbality of enzymes in the
      macromolecular form. The authors present arguments denying the unexceptional
      validity of this dogma. The histological, radiological, biochemical
      (chromatographical, enzymological), immunological and biological methods have
      convincingly proven that a part of swallowed enzymes may pass the intestinal
      barrier in an undamaged macromolecular form and realize their activities in the
      body. The most important elements able to absorb macromolecules seem to be so
      called "M-cells" (FAE) which cover lymphoid foci of the organized gut lymphoid
      tissue. Other mechanisms of enzyme resorption are under discussion. The absorbed
      enzymes are rapidly complexed with naturally occurring blood antiproteases. In
      these complexes the potential immunogenicity of enzymes is restricted and they
      are concentrated into pathologically affected areas of the body. Complexes in
      addition display important immunoregulatory activities.

PMID- 7585875
TI  - Human genome--chromosome no. 19.
AB  - Chromosome 19 is short but has higher relative density of genes than other
      chromosomes. Increasing number of the genes coding for proteins implicated in the
      pathogenesis of various human diseases have been mapped on chromosome 19.
      Mutations of low density lipoprotein receptor (LDL-R) result in one of the most
      frequent mendelian inherited disorder-familial hypercholesterolemia. Mutations of
      insulin receptor (INSR) are causative for rare syndromes of insulin resistance
      and some of non insulin dependent diabetes mellitus (NIDDM). Erythropoietin
      receptor (EPOR) mutations are causative for rare primary familial and congenital
      polycythemias (PFCP). Defects of one of the largest gene in the human genome RYR
      1 (ryanodine receptor gene) (> 240 kb in size) accounts for majority of malignant
      hyperthermia (MH) and central core disease (CCD). All these disorders represent
      group of receptor diseases. The amplification of GCT trinucleotide repeats in
      myotonic dystrophy protein kinase (DMPK) gene is causative for myotonic dystrophy
      (DM) and represents a new class of human gene mutations: trinucleotide repeat
      mutations. Apolipoprotein E (APOE) locus plays a role in pathogenesis of the late
      onset familial Alzheimer's disease. Translocation of EA2 gene which encodes two
      helix-loop-helix (HLH) transcription proteins and its fusion with PBXI or hepatic
      leukemia factor (HLF) leads to the leukemogenesis in subgroup of ALL.
      Interestingly adeno-associated virus (AAV), currently widely used as vector for
      gene therapy has unique capability of specific integration into human chromosome
      19q.

PMID- 7585877
TI  - [The ugly word "euthanasia"].

PMID- 7585876
TI  - [Normal blood values in the adult population in the Czech Republic].
AB  - In a group of 2033 healthy subjects-1475 men, mean age 36 years and 558 women
      mean age 51 years-normal values of the haemogram of the present healthy Czech
      population were assessed. Men: Hb 135-174 g/l, haematocrit 0.39-0.51, Ery 4.19
      5.75 x 10(12)/l, MCV 82.6-98.4 fl, Leuco 4.1-10.2 x 10(9)/l, thrombocytes 142-327
      x 10(9)/l. Women: Hb 116-163 g/l, haematocrit 0.33-0.47, Ery 3.54-5.18 x
      10(12)/l, MCV 82.3-100.6 fl, Leuco 4.0-10.7 x 10(9)/l, thrombocytes 131-364 x
      10(12)/l. When examining the haemogram it is necessary, if possible, to adhere to
      a standard procedure. Results must be always evaluated in conjunction with
      anamnestic data, the physical finding, and possible slightly abnormal values may
      not be always evaluated as pathological.

PMID- 7585878
TI  - [100 years since the discovery of roentgen rays].

PMID- 7585879
TI  - Inhibition of secretion from isolated rat alveolar epithelial type II cells by
      the cell permeant calpain inhibitor II (N-acetyl-leucyl-leucyl-methioninal).
AB  - Although several signal transduction pathways, including activation of specific
      protein kinases have been proposed and studied for the secretory processes of
      lung surfactant from alveolar epithelial type II cells, the role of proteolytic
      processing by calpains (calcium-activated neutral proteases) in secretion has not
      been investigated. Therefore, we examined the effect of cell permeable calpain
      inhibitor I (N-acetyl-leucyl-leucyl-norleucinal) and II (N-acetyl-leucyl-leucyl
      methioninal) on secretion to test the hypothesis that calpains participate in the
      secretory processes of alveolar epithelial type II cells. Calpain inhibitor I
      preferentially inhibits micro (mu)-calpain while inhibitor II inhibits milli (m)
      calpain. Isolated type II cells were prelabelled with [3H]-choline for 18-24 h.
      To measure secretion, [3H]-labelled disaturated phosphatidylcholine (DSPC)
      released in the medium was monitored. Basal secretion of DSPC was maximally (87%)
      depressed by the presence of 10 microM inhibitor II. Secretagogue-stimulated
      secretion was also modulated by inhibitor II treatment. Stimulation with calcium
      ionophore A23187 enhanced secretion 3-fold. However, cells pre-exposed to
      inhibitor II displayed a 90% reduction of calcium-stimulated secretion.
      Terbutaline (10 microM) and ATP (1 mM) each increased secretion 2- and 4-fold,
      respectively. However, the inhibitor-treated cells, exposed to the same stimuli,
      attained only 53 or 62% of these increases. Calpain inhibitor I, on the other
      hand, inhibited neither basal nor stimulated secretion. The results suggest that
      m-calpain, the major isozyme of lung calpain requiring mM calcium for activity in
      vitro, is involved in the secretory pathways of alveolar epithelial type II
      cells.

PMID- 7585881
TI  - Addition of calmodulin antagonists to NRK cells during G1 inhibits proliferating
      cell nuclear antigen expression.
AB  - The mRNAs of most proteins involved in DNA synthesis show an S phase correlated
      expression when mammalian cells are stimulated to proliferate from G0. This is
      the case for proliferating cell nuclear antigen (PCNA), a cofactor of DNA
      polymerase delta that is essential for the synthesis of the leading and lagging
      strands of DNA. Normal rat kidney cells re-entering the cell cycle from
      quiescence start DNA synthesis at 12 h and reach a maximum at 20 h. The
      expression of PCNA parallels the synthesis of DNA. Progression through the S
      phase was inhibited by addition of the anticalmodulin drug W13 to the cells
      during G1, 5 h after activation. W13 also inhibited the increase in both PCNA
      protein and mRNA indicating that calmodulin regulates its expression. Using TK
      ts13 cells transfected with a plasmid containing the thymidine kinase gene under
      the control of the human 2.8 kb PCNA promoter, we demonstrated that this promoter
      is not regulated by calmodulin. The half-life of PCNA mRNA during G1/S transition
      was not modified by the treatment with W13, indicating that the decrease in the
      mRNA found when calmodulin was inhibited is not due to changes in its stability.
      Run-on assays revealed that control cells produced predominantly complete PCNA
      transcripts during S phase, while short incomplete transcripts were generated in
      W13-treated cells at the same time. These results indicate that calmodulin
      participates in a more direct or indirect way during G1 in the activation of PCNA
      expression. From data presented here it can be suggested that calmodulin
      activates the release of a transcriptional block leading to an increase in the
      amount of PCNA during S phase.

PMID- 7585880
TI  - Hormone-regulated Ca2+ channel in rat hepatocytes revealed by whole cell patch
      clamp.
AB  - An inward current responsible for hormone regulated Ca2+ entry has been
      identified in cultured rat hepatocytes using whole cell patch clamp. Addition of
      20 nM vasopressin or of 100 microM ATP induced the inward current, which could be
      observed more clearly after blocking an outward K+ current. This large outward K+
      current, which appeared after addition of vasopressin or ATP, could be blocked
      either by replacing K+ with Cs+ in the external medium and in the pipette
      solution, or by simply including 0.5 microM apamin in the K(+)-containing
      external medium. The outward current appears to be carried by a Ca2+ activated K+
      channel. In the presence of apamin, hepatocytes pretreated with vasopressin in a
      Ca(2+)-free media reveal an inward current on addition of external Ca2+ (5 mM).
      The current could also be elicited by addition of vasopressin when cells are
      preincubated in the presence of 5 mM external Ca2+. No current is seen on
      addition of Ca2+ in the absence of vasopressin. Initially, the inward current was
      ca 200-300 pA at -60 mV, but it declined rapidly over 3 min to ca 20 pA. The
      current approached zero, as an asymptote at positive potential, and appeared to
      be somewhat inwardly rectifying. Additions of 5 mM Mn2+ or 5 mM Ba2+ in place of
      Ca2+ produced little or no current. An inhibitor of ER Ca(2+)-ATPase,
      thapsigargin, could also trigger the cascade of events leading to plasma membrane
      conductance of Ca2+. The data suggest that hormone-stimulated Ca2+ entry into
      hepatocytes is mediated by a Ca(2+)-release activated channel highly specific for
      Ca2+. This is the first demonstration of such a channel in hepatocytes, though
      similar ones have been described in mast cells, in vascular endothelial cells and
      T-lymphocytes.

PMID- 7585883
TI  - Intracellular calcium transients in suctorian protozoa (Trichophrya spp.):
      correlation with spontaneous tentacle contractions.
AB  - The luminescent photoprotein aequorin was used to measure intracellular free Ca2+
      in three species of suctorian protozoon, Trichophrya riederi, Trichophrya collini
      and Trichophrya rotunda. Resting [Ca2+]i ranged from about 75-110 nM, and was
      unaffected by a change in temperature of the perfusate. Spontaneous Ca2+
      transients were observed in all three species, with peak amplitudes ranging from
      100-600 nM. In T. riederi and T. rotunda, three categories of transient (small,
      intermediate, large) were recorded; T. collini displayed only small transients.
      In both T. riederi and T. collini, raising the temperature from 5 degrees to 26
      degrees C led to an increase in the frequency of transients. Furthermore, in T.
      riederi, large transients occurred only at the higher temperature. The frequency
      of spontaneous contractions of the tentacles of T. riederi was also temperature
      dependent. Increasing the temperature over the range 5-26 degrees C led to a
      concomitant increase in contraction frequency and a decrease in mean tentacle
      length. The possible mechanisms of spontaneous Ca2+ transient generation and
      their role in the control of contraction are discussed.

PMID- 7585882
TI  - Acetylcholine-activated inward current induces cytosolic Ca2+ mobilization in
      mouse C2C12 myotubes.
AB  - We examined the spatiotemporal pattern of intracellular Ca2+ liberation in mouse
      myotubes by means of fluorescence imaging of cytosolic free Ca2+ together with
      the simultaneous recording of membrane whole-cell currents. Acetylcholine (ACh)
      applications to C2C12 myotubes equilibrated in Ca(2+)-free medium and voltage
      clamped at -50 mV evoked localized fluorescence transients of variable amplitude
      with less than 0.5 s delay. Under the same experimental conditions, fluorescence
      transients were elicited by ACh also in mouse primary myotubes. Ca2+ transients
      were inhibited in myotubes clamped at depolarized potentials (-10 mV to +50 mV),
      or equilibrated in a Na+,Ca(2+)-free medium as well as in cells loaded with
      heparin, or with inositol (1,4,5) trisphosphate (InsP3). To investigate whether
      InsP3 could induce Ca2+ mobilization, [Ca2+]i determinations were carried out in
      myotubes loaded with InsP3 through the whole-cell patch-clamp recording pipette
      or by extracellular application in permeabilized cells. InsP3 diffusion into the
      myoplasm caused Ca2+ spikes with 5 +/- 1 s (mean +/- SEM) delay from the rupture
      of the membrane patch. Spikes were followed by sustained increases in
      fluorescence or by damped oscillations. In permeabilized myotubes, InsP3 induced
      the release of sequestered 45Ca2+ with a half-maximally effective concentration
      (EC50) of 0.28 +/- 0.05 microM, and Hill coefficient of 0.79 +/- 0.09. It is
      concluded that the ACh-activated inward current in mouse myotubes is coupled to
      cytosolic Ca2+ mobilization from internal InsP3-sensitive pools.

PMID- 7585885
TI  - Inhibition of the sarcolemmal Ca2+ pump in embryonic chick heart cells by mini
      glucagon.
AB  - The effect of mini-glucagon, the metabolite (19-29) of glucagon was examined on
      the sarcolemmal (SL) Ca2+ pump activity measured in situ, in single quiescent
      embryonic chick heart ventricular cells loaded with Fura-2. The method consisted
      in triggering limited cytosolic Ca2+ concentration ([Ca2+]i) pulses by the
      addition of the Ca2+ ionophore 4-bromo-A23187. [Ca2+]i decays, imposed by the
      addition of EGTA, were monitored in conditions in which only the SL Ca2+ pump
      could ensure [Ca2+]i removal, i.e. in the presence of the sarcoplasmic reticular
      (SR) Ca2+ pump specific inhibitor, thapsigargin, substituting NaCI by LiCI in the
      external medium in order to quench the Na+/Ca2+ exchanger, and under null Ca2+
      gradient. Mini-glucagon elicited a dose-dependent inhibition of the SL Ca2+ pump,
      maximal 80% inhibition being observed with 1 nM mini-glucagon. In addition to its
      effect on the SL Ca2+ pump, mini-glucagon evoked a delayed onset of a [Ca2+]i
      oscillatory response in cells incubated in normal conditions. Both effects of
      mini-glucagon were mimicked by vanadate tested at 2 microM, a concentration at
      which it acts as a specific inhibitor of the SL Ca2+ pump. These results define
      the contribution of the cardiac sarcolemmal Ca2+ pump to Ca2+ homeostasis in situ
      and its role as a target for mini-glucagon action.

PMID- 7585884
TI  - Possibility of simultaneously measuring low and high calcium concentrations using
      Fura-2 and lifetime-based sensing.
AB  - We characterized the fluorescence probe Fura-2 for calcium measurements using
      frequency-domain phase-modulation fluorometry. By the use of different excitation
      wavelengths from 345 to 380 nm, the apparent calcium dissociation constants can
      be altered from 41 nM to 1.92 microM Ca2+. This change in apparent Kd results
      from changes in the relative extent of excitation of the calcium-bound and
      calcium-free forms, and the excitation wavelength-dependent contribution of each
      form to the intensity decay. These results indicate that lifetime-based
      measurements with Fura-2 can be used for imaging of calcium over a wide range of
      concentrations. An additional favorable feature of Fura-2 is that the calcium
      free form can be almost exclusively excited at wavelength of 390 nm or longer,
      and can thus be used as a reference providing the lifetime in the absence of
      calcium, without removing the calcium. Additionally, exposure of Fura-2 to
      intense illumination shifts but does not distort the frequency response. For
      cellular imaging, these favorable properties of Fura-2 may allow calibration of
      the calcium concentrations without the use of ionophores.

PMID- 7585886
TI  - Intracellular calcium release induced by human immunodeficiency virus type 1 (HIV
      1) surface envelope glycoprotein in human intestinal epithelial cells: a putative
      mechanism for HIV-1 enteropathy.
AB  - Intracellular Ca2+ ([Ca2+]i) was measured in single human epithelial intestinal
      HT-29-D4 cells with the Ca2+ probe Fura-2 and digital imaging microscopy.
      Treatment of these cells with HIV-1 surface envelope glycoprotein gp120 (or a
      soluble form of its precursor gp160) induced an important increase of [Ca2+]i.
      This effect was abolished by preincubation of the viral glycoprotein with
      neutralizing antibodies specific for the V3 domain of gp120. These antibodies
      inhibited the binding of both gp120 and gp160 to galactosylceramide (GalCer), the
      alternative HIV-1 receptor in HT-29-D4 cells. Moreover, treatment of HT-29-D4
      cells with an anti-GalCer mAb induced an increase in [Ca2+]i and rendered the
      cells insensitive to HIV-1 glycoprotein stimulation. The calcium response
      resulted from release of Ca2+ from caffeine-sensitive intracellular stores.
      Finally, the viral glycoprotein specifically abrogated the calcium response to
      the neuropeptide agonist neurotensin, a stimulator of chloride secretion via
      inositol trisphosphate-mediated calcium mobilization. Reciprocally, after
      neurotensin stimulation, the cells did not respond to gp120, showing that
      neurotensin and gp120 stimulate a common pathway of [Ca2+]i mobilization. These
      results suggest that HIV-1 may directly alter ion secretion in the intestine and
      thus be the causative agent of the watery diarrhea associated with HIV-1
      infection.

PMID- 7585887
TI  - Slow kinetics of InsP3-induced Ca2+ release: differences between uni- and bi
      directional 45Ca2+ fluxes.
AB  - The effects of a long-lasting stimulation with inositol 1,4,5-trisphosphate
      (InsP3) have been studied in monolayers of permeabilized A7r5 cells. When
      measured under unidirectional 45Ca2+ efflux conditions, i.e. in the presence of 2
      microM thapsigargin, an initial fast release was observed which then
      progressively slowed down into a slow phase which persisted for up to 20 min.
      When measured under bidirectional 45Ca2+ flux conditions with functional Ca2+
      pumps, a transient phase of re-uptake occurred between the initial fast and the
      subsequent slow release phase. These kinetics are compatible with intrinsic
      inactivation of the InsP3 receptor. However, this inactivation did not prevent
      the slow release component. The slow component was not due to the accumulation of
      an InsP3 metabolite nor to a GTP-dependent translocation of Ca2+ between stores.
      The slow release phase was more pronounced when the Ca2+ pumps were active than
      when they were inhibited. This observation is compatible with other findings
      indicating that the InsP3 receptor is controlled by luminal Ca2+. The decreasing
      effectiveness of a 20 min lasting InsP3 challenge in mobilizing Ca2+ from less
      filled stores is most likely due to a progressive depletion of the store and
      cannot be considered as an experimental artifact caused by a preferential
      emptying of InsP3-sensitive Ca2+ stores. We conclude that the InsP3 receptor can
      intrinsically inactivate but that this inactivation is unable to prevent the slow
      release, which is especially pronounced when Ca2+ pumps are active.

PMID- 7585889
TI  - Activation of Ca2+ influx by transforming Ha-ras.
AB  - The effect of an induction of transforming Ha-ras on Ca2+ influx into NIH3T3
      cells was studied employing Fura-2 quenching by Mn2+. The expression of
      transforming p21Ha-ras caused a significant increase in Mn2+ influx which was
      blocked by Cd2+, La3+, niguldipine and the Ca(2+)-channel blocker SK&F96365. This
      effect was specific for transforming Ha-ras and was not seen after overexpression
      of the Ha-ras proto-oncogene or v-mos. In addition to the enhanced Mn2+ influx,
      transforming p21Ha-ras elicited an increased efflux of the K(+)-congener 86Rb+
      which was inhibitable by Ca(2+)-channel blockers and charybdotoxin, a selective
      inhibitor of high and intermediate conductance Ca(2+)-dependent K+ channels.
      Charybdotoxin did not reduce the increase in Mn2+ influx by ras, demonstrating
      that the activation of Ca(2+)-dependent K+ channels was not required for the
      sustained Mn2+/Ca2+ influx in the presence of transforming Ha-ras. In ras
      expressing cells, the bradykinin-induced Mn2+ influx and charybdotoxin sensitive
      86Rb+ efflux were markedly potentiated. The increase in the inositol- 1,4,5
      trisphosphate and inositol-1,3,4,5-tetrakisphosphate levels by ras is not
      sufficient to explain the elevated Mn2+ influx. The mitogenic response to an
      expression of transforming Ha-ras was inhibited by the Ca(2+)-channel blockers
      not, however, by charybdotoxin. These data suggest the existence of an agonist
      independent activation of a receptor- or second messenger-operated Ca2+ channel
      by transforming Ha-ras which is necessary for the mitogenic response to the
      activation of the oncogene.

PMID- 7585890
TI  - The effect of furosemide on calcium ion concentration in myocardial cells.
AB  - The effect of furosemide and ouabain on the intracellular concentration of Ca2+
      was studies in myocardial cell cultures using Fura-2, a fluorescent agent, as an
      intracellular Ca2+ indicator. Introduction of 200 microM ouabain to the cultured
      cells increased the intracellular calcium concentration from an average of 236 nM
      up to an average of 833 nM. Introduction of 100 microM furosemide, prior to the
      administration of ouabain, decreased the ouabain induced Ca2+ elevation to an
      average of only 473 nM. Introduction of 2.5 mM EGTA prior to the administration
      of ouabain abolished the ouabain induced Ca2+ increase.

PMID- 7585892
TI  - Contractile and intracellular Ca2+ decay in potentiated contractions following
      multiple extrasystolic beats.
AB  - Developed pressure and intracellular Ca2+ ([Ca2+i) decay in postextrasystolic
      beats following multiple extrasystolic contractions (ESCs) was evaluated with
      surface fluorometry in atrioventricular-blocked perfused rat hearts loaded with
      Indo-1. After priming pacing at 400 ms intervals, 1-25 ESCs were interposed with
      a 160 ms interval, followed by 30 postextrasystolic beats with a 400 ms interval.
      Both left ventricular developed pressure and the amplitude of the Indo-1
      fluorescence ratio (F400/F510: an index of [Ca2+]i) increased in a
      monoexponential manner with an increase in the number of ESCs. Both potentiated
      left ventricular developed pressure and the amplitude of F400/F510 transients
      returned to control in a monoexponential fashion. Consistent with this
      exponential decay, the relationship between developed pressure or the amplitude
      of F400/F510 transients in a postextrasystolic beat and that in the preceding
      beat was linear and the slope of a fitted line (recirculation fraction; RF) was
      evaluated as an index of rapidity of decay. The number of ESCs did not affect RF
      of developed pressure and the amplitude of F400/F510 transients. Reducing
      extracellular Ca2+ concentration (1.25 --> 0.55 mM), and perfusion with an acidic
      solution (pH = 6.8) significantly decreased RF of both developed pressure (0.85
      +/- 0.06 --> 0.78 +/- P < 0.05 and 0.85 +/- 0.07 --> 0.78 +/- 0.06, n=8, P <
      0.05, respectively) and the amplitude of F400/F510 (0.87 +/- 0.06 --> 0.78 +/-
      0.05, P < 0.05, and 0.89 +/- 0.08 --> 0.78 +/- 0.07, P < 0.05, respectively).
      This study confirmed that, in all conditions evaluated, contractile decay was
      determined by [Ca2+]i decay and RF of contractile decay was an accurate estimate
      of [Ca2+]i decay in physiologically paced isolated perfused rat hearts.

PMID- 7585893
TI  - Glucose induces oscillations of cytoplasmic Ca2+, Sr2+ and Ba2+ in pancreatic
      beta-cells without participation of the thapsigargin-sensitive store.
AB  - Individual pancreatic beta -cells were used to study the glucose effects on the
      handling of Ca2+, Sr2+ and Ba2+. In extracellular medium containing one of these
      ions, single beta -cells responded to 11 mM glucose with large amplitude
      oscillations in cytoplasmic Ca2+, Sr2+ or Ba2+ with indistinguishable average
      frequencies (0.30-0.33/min). The oscillations disappeared after hyperpolarization
      with 400 microM diazoxide. Under such hyperpolarization, glucose stimulated the
      sequestration of Ca2+ and Sr2+ but not of repetitively mobilized by consecutive
      exposures to 100 microM carbachol. A 2-3 min exposure to 100 nM of the
      intracellular Ca(2+)-ATPase inhibitor thapsigargin also mobilized Ca2+ and Sr2+
      and irreversibly abolished subsequent release by carbachol. However, thapsigargin
      did not prevent the large amplitude oscillations in Ca2+, Sr2+ or Ba2+ under non
      hyperpolarizing conditions although the frequency of the Ca2+ oscillations was
      almost doubled. The results indicate that the slow oscillatory behavior of
      glucose-stimulated individual beta -cells does not depend on inositol 1,4,5
      trisphosphate mediated release of intracellular Ca2+.

PMID- 7585888
TI  - Human cytomegalovirus modulates the Ca2+ response to vasopressin and ATP in
      fibroblast cultures.
AB  - The free calcium concentrations in the nucleus ([Ca2+]n) and in cytosol ([Ca2+]c)
      of cultured human embryonic lung (HEL) fibroblasts were estimated by confocal
      laser microscopy using the Ca(2+)-indicator Indo-1. In resting HEL cells, The
      free cellular Ca(2+)-concentration significantly increased upon human
      cytomegalovirus (HCMV) infection. The ratio between [Ca2+]n and [Ca2+]c was not
      affected. Following stimulation by ATP or [Arg8] vasopressin (AVP), a
      differential Ca2+ response of the HCMV-infected HEL cells was observed. While
      uninfected cells were highly sensitive to AVP and only poorly sensitive to ATP,
      infected cells showed a high responsiveness to ATP but not to AVP. This switch in
      sensitivity to the agonists first observed at 24 h post infection. The Ca(2+)
      rise following ATP or AVP stimulation was derived from intracellular Ca2+ stores.
      The magnitude of the ATP-induced Ca(2+)-rise increased upon infection. In
      contrast to non-infected cells where [Ca2+]n > [Ca2+]c during stimulation with
      AVP or ATP, no nucleo-cytosolic Ca(2+)-gradient was observed in infected cells.
      Furthermore, the magnitude of the Ca2+ rise in the two compartments was higher in
      ATP-stimulated cells. It is concluded that HCMV infection significantly
      interferes with Ca(2+)-homeostasis in HEL cells which could be related to the
      pathogenesis of the disease.

PMID- 7585895
TI  - [Trend and prediction of cancer mortality in Beijing, China, during 1980-2001].
AB  - Mortality data gathered through registration system were analyzed systematically
      to predict the trend of cancer mortality. A grey-system model was established to
      forecast the epidemic trend for cancer mortality of Beijing in 2001. In result,
      the mortality of cancer in Beijing will increase annually upto 2001. The
      composition of various malignant tumer will charge notably. Rapid increase will
      occure in lung cancer. Liver cancer and colon-rectal cancer will aslo increase.
      Cancers of esophagus and cervix uteri will steadly decline. Stomach cancer begin
      to decrease. These information on the change of cancer mortality will provide
      scientific reference for the study of cancer prevention and control in Beijing.

PMID- 7585894
TI  - Calcium mobilization and entry induced by extracellular ATP in the non-sensory
      epithelial cell of the cochlear lateral wall.
AB  - Effects of external ATP application on the intracellular Ca2+ concentration
      ([Ca2+]i) of the epithelial lining cells of the cochlear lateral wall, the stria
      vascularis (SV), spiral prominence (SP), and external sulcus (ES) cells, were
      examined by the fluorescent Ca2+ indicator, Fura-2. ATP induced an increase in
      [Ca2+]i of these epithelial cells loaded with Fura-2 in a dose-dependent manner
      (1-100 microM). The strongest response was observed in SP and ES cells, whereas
      SV cells showed a weak response. The increase in [Ca2+]i was a biphasic response
      consisting of a rapid transient peak followed by a sustained phase. Removal of
      the external Ca2+ caused a slight transient increase in [Ca2+]i without a
      subsequent sustained phase. The Mn2(+)-quenching method revealed the Ca2+ entry
      across the plasma membrane immediately after the ATP application. The initial
      peak results from both the release of Ca2+ from intracellular stores and the Ca2+
      influx from the extracellular space. The sustained phase is totally derived from
      the external Ca2+. The effective order of purinergic agonists was 2-methylthio
      ATP > or = ATP > 3'-O-(4-benzoyl)benzoyl ATP > alpha, beta-methylene ATP > or =
      ADP, but adenosine or UTP showed no response. The ATP-induced [Ca2+]i response
      was inhibited by reactive blue 2. The [Ca2+]i was partially dependent on the
      concentration of the fully ionized form, ATP-4. These findings indicate the
      presence of both P2y- and P2z-purinergic receptors in the non-sensory epithelial
      cells of the lateral wall.

PMID- 7585891
TI  - Voltage control of calcium transients elicited by caffeine and tetracaine in
      cultured rat muscle cells.
AB  - Cultured hind limb skeletal muscle cells from newborn rats were used to study the
      effect of caffeine and tetracaine upon intracellular Ca2+ release under voltage
      or current clamp conditions. Free [Ca2+]i was measured using the fluorescent
      calcium-sensitive dye Fluo-3. A field containing one or several myotubes was
      observed with a video camera and image analysis of fluorescence changes was
      performed. Addition of 100-500 microM tetracaine to the external saline elicited
      strong fluorescence responses in non-clamped cells, but significantly lower
      responses in cells clamped at -90 mV. At the same time, tetracaine inhibited
      voltage induced calcium release. Voltage and tetracaine modulation over the
      action of caffeine (500 microM) was also observed. Pretreatment of cells with 10
      microM nifedipine abolished the caffeine induced fluorescence response in non
      clamped cells. These findings suggest that, in cultured muscle cells, calcium
      release through the caffeine and tetracaine sensitive pathways is controlled by
      both membrane potential and the dihydropyridine receptor.

PMID- 7585898
TI  - [A study on serotypes of U. urealyticum isolated from different populations].
AB  - This is a study on serotypes 1-14 Ureaplasma urealyticum (Uu) infections of
      genitourinary in different populations. The results show that 1) the Uu infection
      rate is the highest in sexually promiscuous persons with STDs (78/115, 67.83%),
      lesser in both sexually promiscuous persons without STDs (97/185, 52.43%) and in
      general population with common genitourinary infections (84/180, 46.67%), and the
      lowest in healthy controls (73/320, 22.81%); 2) all of the 14 serotypes and
      untypeable Uu infections existed in China are identified; 3) the relationship
      between Uu 1 and 4 serotype and infections is stronger, but medium strong in 2, 8
      and 10 serotype, whereas, 3, 9 and 14 serotype are major colonizational strains;
      4) multi-serotypes infections are closely associated with sexually promiscuous
      behaviour.

PMID- 7585896
TI  - [A matched case-control study on the relations between beta-carotene and lung
      cancer].
AB  - In order to discover the relationship between dietary nutrients intake and risk
      of lung cancer 1:1 matched case-control study on 156 recent histologiclly
      diagnosed primary lung cancer patients and 156 patients with respiratory tumour
      and other related diseases as controls, was conducted in Wuhan. All cases and
      controls were asked to participate in the nutritional assessment program and a
      food frequency questionnaire containing 64 food items was filled in. The findings
      showed that there was a statistically significant difference between dietary
      intake of beta-carotene between the two groups (2877.13 +/- 393.43 vs. 3445 +/-
      430.98 micrograms/day). Having controled the confounding factor of cigarette
      smoking, a significant linear trend for lower dietary carotene intake toward
      higher lung cancer risk was observed.

PMID- 7585897
TI  - [An analysis of relationship between mortality of cancer and age-period-cohort].
AB  - The APC (age-period-cohort analysis) model makes the assumption that the
      mortality mij in a given age-group and year is the (simple) product of three
      factors: an age-related factor ai, one period-related factor bj and one (birth)
      cohort-related factor Ck: mij = eai x ebj x eck. By taking the natural logarithm,
      a linear model results which can be treated with fairly standard statistics
      techniques: ln (mij) = ai+bj+ck. The mij data from observation data are used to
      estimate alpha, beta(a), beta(b), beta(c) by linear regression method. The value
      of EXP (beta) is to estimate the effect of each variable. The APC model is
      consistent with carcinogenesis modeling of molecular biology on tumour. The
      results of APC analysis for cervical cancer, male and female stomach cancer show
      that the risk factors have been changed. In fact, the risk factors of cervical
      cancer have been decreased since liberation, and the risk factor of stomach was
      increased in the first period of sixty's. The analytic method used in this paper
      will benefit the study on epidemiology and etiology of cancer.

PMID- 7585899
TI  - [Investigation of cervical Chlamydia trachomatis infection in gynecologic
      outpatients].
AB  - A group of 662 women in our gynecologic OPD were screened for Chlamydia
      trachomatis with direct immunofluorecence monoclonal antibody (DFA) staining
      technique. Their age distribution ranged from 16 to 60 years old. The overall
      positivity rate was 26.3%. Of the 269 pregnant women, 64 cases were found to have
      Chlamydia trachomatis infection, an infection rate of 23.74%. There was no
      statistically significant difference of infection rates among age groups. In the
      positive group, however, the rate of infertility was 25.43%, much higher than
      that in the negative group (12.88%, P < 0.01). And there was no statistical
      significance of infection rates between patients taking contraception and those
      did not. A positive correlation existed between the degree of cervicitis and the
      Chlamydia trachomatis infection.

PMID- 7585900
TI  - [Seroepidemiological study of HBV and HCV infection in sexually promiscuous
      groups].
AB  - A serological study on the detection of HBV and HCV infection markers and the
      investigation of related sexual behaviors were conducted among 431 female
      prostitutes and 109 normal women. The result showed of anti-HBc prevalence rate
      was 43.1% (186/431), anti-HBs positive rate was 36.9% (159/431), HBsAg positive
      rate was 11.1% (48/431) and anti-HCV positive rate 9.51% (41/431). They were all
      significantly higher in prostitutes than in normal women. The infection indexes
      of HBV and HCV were also higher in population with STD than in normal women. The
      prevalence of anti-HCV in female prostitutes tended to increase with increase of
      age. There was a significant correlation with the number of their clients and
      years of being prostitutes. This demonstrated that there was a relatively high
      HBV and HCV infection rates in prostitutes.

PMID- 7585902
TI  - [A study on the implementation of primary chemotherapy to pulmonary tuberculosis
      with positive bacillus].
AB  - A cohort study on chemotherapy implementation program with regards to newly
      detected bacillus positive pulmonary tuberculosis patients in 132 medical units
      was carried out. Results showed that a) one year sputum negative conversion rate
      was 80%; b) only 48.1% of the patients had received the standardization six-
      month short--course chemotherapy regimens promoted by M. O. H; c) among 60% of
      the patients the duration of treatment had been too long; d) the two--year
      relapse rate of initial drug--resistant patients was 7.6%. The result suggested
      that the standardized chemotherapy program should be strenghened.

PMID- 7585901
TI  - [The study of Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma
      urealyticum infection status by polymerase chain reaction].
AB  - The study involved 355 specimens of STD clinic patients collected from Beijing,
      Shantou and Wuhan, for the detection of Neisseria gonorrhoeae, Chlamydia
      trachomatis, Ureaplasma urealyticum by polymerase chain reaction. The results
      showed that the positive rate of Neisseria gonorrhoeae being the highest in the
      patients attending STD clinics from the three cities. The detection rate of
      Neisseria gonorrhoeae in male patients was higher than in females. The positive
      rates of Chlamydia trachomatis and Ureaplasma urealyticum in the three cities
      differed from each other greatly. Polymerase chain reaction was suitable for
      clinical Jetection and epidemiological study of the three kinds of STD pathogens.

PMID- 7585903
TI  - [Seroepidemiological surveillance and methodological study of pertussis,
      diphtheria and tetanus].
AB  - In this paper, we studied the diagnostic method of DPT using PA method developed
      by Japanese National Institute of Health (NIH) in 1993-1994, meanwhile we
      surveyed the antibody level of DPT. We collected 900 sera samples and 300 sera
      samples from Hebei province in 1993 and 1994. The result showed that PA method
      was simple, reliable and easy to observe, which can make up the shortages existed
      in PHA method. The antitoxin titers obtained by the PA method correlated well
      with the PHA method, while the latter was more sensitive. The antibody level of
      pertussis obtained through PA method did not correlate well with MA method. The
      result also showed that the antibody level of DPT was not high, with a 95.0%
      positive rate of pertussis. The rate of titers higher than 1:320 was 4.7% with
      GMT 1:121; the positive rate of diphtheria was 62.9% with GMT 0.0280 IU/ml, in
      1993 the positive rate of tetanus was 70.5% with GMT 0.1410 IU/ml, in 1994 the
      positive rate was 75.7% with GMT 0.3281 IU/ml. The titers in urban areas were
      higher than in rural areas and a decrease was observed with the increase of age.
      The titers in males was similar to in females. According to this result, a
      routine immunization followed by booster program should be emphasized.

PMID- 7585904
TI  - [A discussion on setting up target age group for immunization against
      leptospirosis].
AB  - This paper presented the lesson of setting up a false immunization priority age
      group for leptospirosis which failed to prevent the leptospirosis outbreak. Our
      experience was that in the rice paddy field type endemic area the priority age
      group for the vaccination against leptopirosis should be 15 to 34 year olds
      followed by 35 years old or above. There was no preventive effect in the
      vaccination for the children 14 years old or yaunger, to our observation.

PMID- 7585905
TI  - [Analysis of nosocomial infection in hospitalized critical and serious patients].
AB  - An investigation was made on 298 hospitalized critical and serious patients in
      Chongqing. the results showed that the nosocomial infection rate was 43.3%
      (129/298). The higher infection rate was found in the departments of brain
      surgery and hematopathy. The lower respiratory tract was found to be the most
      commonly seen infection sites (65.1%). Of 46 strains of the pathogenic organisms
      causing the nosocomial infection, gram-negative becilli were accounted for 52.2%
      and fungi 28.3%. The case fatality rate of infected patients (37.9%) was
      significantly higher than that of non-infected patient's (10.7%).

PMID- 7585908
TI  - [Epidemiological status of alveolar echinococcosis in China].

PMID- 7585906
TI  - [Epidemiological study of hepatitis C virus (HCV) infection in plasmapheresis and
      blood donors].
AB  - We actively adopted method to control hepatitis C (HC) epidemic in blood
      sampling. ELISA was used to detect anti-HCV antibody in different groups of 2348
      blood donors. The positive rates of anti-HCV for plasmaphersis and whole blood
      donors were 0.58% (2/343) and 1.34% (27/2005) respectively, with no statistical
      significance (P > 0.05). The positive rates of anti-HCV for plasmapheresis donors
      in 1-2 years and over 9 years were 0.99% (7/701) and 0.74% (2/270) respectively.
      There was no significant difference (P > 0.05) either. The positive rates of anti
      HCV for plasmapheresis donors in 1992 and in 1994 were 1.64% (7/426), and 0.58%
      (2/343). The results showed that HCV infection rate did not increase in
      plasmapheresis donors, nor did it increase parallel with the increasing gears of
      blood donnation.

PMID- 7585910
TI  - Questioning the level of efficacy of the measles vaccine in use in Zimbabwe.
AB  - A prospective study was carried out between 1987 and 1989 in the City of Gweru
      (Zimbabwe) to assess the efficacy of the measles vaccine. The vaccine efficacy
      assessment was carried out on an epidemiological basis by relating measles
      transmission in the vaccinated and unvaccinated children aged 10 to 23 months.
      Measles cases were identified on the basis of a standard case definition and data
      on occurrence of measles cases was collected through an active surveillance
      system. Efficacies of 73 pc, 82 pc and 77 pc were calculated for the years 1987,
      1988 and 1989 respectively. Over the three year period mean efficacy was found to
      be 77 pc (95 pc confidence interval 75 to 79 pc). The vaccine efficacies found in
      this study were lower than 85 pc which is the officially accepted efficacy of the
      measles vaccine that is in use in Zimbabwe. The low vaccine efficacy found in
      this study is attributed to the fact that the measles vaccine is applied (at nine
      months of age) when probably 10 to 20 pc of children still have prenatally
      acquired maternal antibodies. It is suggested that further studies be carried out
      in Zimbabwe to enable the country to define the way forward.

PMID- 7585907
TI  - [An epidemiological survey on Helicobacter pylori infection in children].
AB  - In this study serum anti-urease antibodies of Helicobacter pylori was examined in
      order to investigate the prevalence of H. pylori infection in 394 children
      between age 1 and 13. The results showed that the average infection rate was
      15.7% with a tendency of increase infection rate with age, and by the age of 12
      the H. pylori infection rate reached 30%, which was higher than those found in
      developed countries. We also noticed that there was a comparatively higher
      serapositivity among 1 and 7 year olds. This may possibly be due to the close
      contact between family members and school mates. In addition, the serum positive
      rate of antibody to H. pylori urease in children with recurrent abdominal pain
      was much higher than those asymptomatic children (P < 0.05).

PMID- 7585912
TI  - Hyperventilation in febrile Nigerian children without pneumonia: an evaluation of
      the influence of anaemia.
AB  - A total of 225 pre-school Nigerians were studied to evaluate the effect of
      anaemia on the respiratory rate of febrile children, and the influence of this on
      the reliability of the WHO criteria for the clinical diagnosis of pneumonia in
      the primary health care setting. Malaria was the commonest cause of febrile
      illness (63.1 pc). The prevalence of severe anaemia was 28.0 pc. The mean
      respiratory rate of anaemic children (53.9 +/- 12.8/min) was significantly higher
      than that of the non-anaemic (48.4 +/- 12.7/min; p = 0.011). Mean body
      temperature was not significantly different in both groups. Haematocrit was
      negatively correlated with respiratory rate. The positive correlation observed
      between temperature and respiratory rate was enhanced by decreasing haematocrit.
      More of the severely anaemic children (68.6 pc) exceeded the WHO respiratory rate
      threshold for diagnosis of pneumonia than the moderately anaemic (55.4 pc) or non
      anaemic (36.1 pc). The specificity of the WHO criteria for clinical diagnosis of
      pneumonia decreased with decreasing haematocrit.

PMID- 7585911
TI  - Ovarian tumours in Africans: a study of 512 cases.
AB  - This paper reports 512 cases of ovarian tumours seen over a 11 year period at Ga
      Rankuwa Hospital. Germ cell tumours constituted 47.8 pc and common epithelial
      tumours formed 29.3 pc of all the tumours. Sixty seven pc (341) tumours had a
      benign histology and 33 pc (171) tumours were histologically malignant. The
      tumours were seen at a younger age than experienced in the Western World.

PMID- 7585913
TI  - Predictive factors for medical students and housemen to work in rural health
      institutions in Zimbabwe.
AB  - A survey was conducted among medical students and housemen in order to identify
      factors associated with the choice of future practice in Zimbabwe. A total of 150
      medical students and housemen participated in the study. The medical students and
      housemen were 6.5 (95 pc CI 1.6-26.6), 4.0 (95 pc CI 1.3-12.8) and 3.2 (95 pc CI
      1.1-9.4) more likely to work in an urban than rural area for at least three years
      because of the prestige in the community, standard of living and salary,
      respectively. Further studies should be done to test whether raising the prestige
      in the community, standard of living and salary in rural areas would attract more
      physicians to work in rural health institutions in Zimbabwe.

PMID- 7585909
TI  - Fine needle aspiration cytology in the diagnosis of hepatocellular carcinoma.
AB  - Fine needle aspiration (FNA) of the liver without ultrasound guidance was
      performed on 110 patients with hepatocellular carcinoma (HCC). The median age was
      52 years, with a range of 16 to 86 years. There were 90 males and 20 females (a
      male: female ratio of 4.5:1), with a median age of 51.5 years (range 16 to 86
      years) and 55.5 years (range 17 to 72 years) respectively. FNA was reported as
      showing malignancy in 92 (84 pc, 95 pc CI 77 to 91 pc) patients; 80 (73 pc) were
      definite HCC, 12 (11 pc) were malignant unspecified, seven (6 pc) were suspicious
      of malignancy, seven (6 pc) had no malignant cells and four (4 pc) were non
      diagnostic. The only complication observed was dizziness in one patient. We
      conclude that FNA of the liver for the diagnosis of HCC is a safe, simple and
      accurate procedure which can be undertaken in settings that would otherwise not
      be suitable for formal liver biopsy.

PMID- 7585914
TI  - Autosomal dominant typical coloboma associated with unilateral pseudoptosis,
      myopia and cataract.
AB  - Ocular coloboma is considered to be hereditary ocular malformation which can
      manifest itself in various conditions ranging from iris defect to rudimentary
      cystic eye globe. We describe a three generation family affected by autosomal
      dominant typical coloboma, unilateral pseudoptosis, myopia and cataract.
      Correction of refractive errors improved their visual performance and prevented
      amblyopia. Genetic consultation was given in order to prevent blindness. We
      recommend a multidisciplinary approach regarding management of colobomatous
      patients.

PMID- 7585915
TI  - Ante-mortem diagnosis of human rabies by the skin biopsy technique: three case
      reports from Zimbabwe.
AB  - Three cases of human rabies were diagnosed antemortem by the skin biopsy
      technique. The skin biopsies were taken from the nape of the neck and processed
      by cryosectioning and staining using the direct fluorescent antibody test (FAT).
      Rabies antigen was demonstrated in the network of nerve fibres surrounding the
      hair follicles. As the skin biopsy technique is relatively simple and cheap to
      perform it could be a practical technique for use in African countries, where it
      is not routinely used in the diagnosis of rabies in humans.

PMID- 7585916
TI  - Bone marrow failure. Pathophysiology and management.

PMID- 7585917
TI  - Parametric or non-parametric: a case for comparing the distribution of a
      continuous variable between two populations using Epi Info.

PMID- 7585918
TI  - Artemether resistant P. falciparum.

PMID- 7585919
TI  - AIDS, Ebola and other new epidemics: theme of European Conference on Tropical
      Medicine in Hamburg.

PMID- 7585920
TI  - Migraine to the year 2000.
AB  - Although migraine is inextricably bound up with 5-hydroxytryptamine and its many
      receptors, its precise mechanisms continue to elude us and there is still no
      clear evidence supporting either a vascular or neurogenic hypothesis
      unequivocally. What appears to distinguish migraine sufferers from normal
      subjects may be a greater gentic sensitivity to a wide variety of triggering
      agents--even including nitric oxide and the migraine aura, as well as those more
      usually recognized. Attention is drawn to a possible role for neurotrophins, such
      as the hyperalgesia-provoking nerve growth factor (NGF) in particular, as well as
      basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor
      (BDNF).

PMID- 7585921
TI  - Platelet models and their possible usefulness in the study of migraine
      pathogenesis.
AB  - Platelets may be linked to migraine. On the one hand they are activated during
      the migraine attack and thus may participate in the pathogenesis of the disorder
      (the nature of this activation is still unknown). In order to understand this
      platelet anomaly, we discuss the data available in the literature. In particular,
      we review recent in vitro studies of alpha-granules and dense bodies secretion,
      and aggregation induced by collagen and PAF. On the other hand, platelets share
      many metabolic characteristics with serotonergic neurons and endothelial cells.
      Accordingly, platelets have been used to investigate the possible role of
      serotonin turnover and nitric oxide function in migraine. In both cases, the data
      obtained have shown peculiar abnormalities that may explain pathogenetic and
      clinical aspects of primary headache.

PMID- 7585922
TI  - Neuropeptides in the cerebral circulation: relevance to headache.
AB  - The article briefly describe the innervation of the human cerebral circulation by
      nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide
      (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). The
      neuropeptides in human cerebral arteries were characterized by radioimmunoassay
      in combination with HPLC. These neuropeptides mediate contraction (NPY) and
      dilation (VIP, SP, CGRP). In conjunction with spontaneous attacks of migraine or
      cluster headache, release of CGRP is seen. With the associated symptoms of nasal
      congestion and rhinorrhea, VIP is released. Successful treatment may abort the
      peptide release in parallel with disappearance of headache.

PMID- 7585923
TI  - Neurogenic model of migraine.
AB  - Activation of peripheral trigeminal fibers induces neurogenic inflammation in rat
      dura mater, as well as vascular and mat cell changes. These changes parallel an
      increase of vasodilating and permeability promoting peptides in venous effluent
      of the cephalic circulation. The experimental model of electrical trigeminal
      ganglion stimulation or systemic capsaicin administration has proven effective in
      detecting cellular activation in brainstem trigeminal nuclei. Animal experimental
      models of trigeminovascular activation and the effects of antimigraine drugs on
      functional and morphological consequences of such activation provide the
      background for further models and for developing pharmacological strategies in
      this field.

PMID- 7585924
TI  - Experimental headache in humans.
AB  - The need for valid human experimental models of headache is obvious. Several
      compounds have been proposed as headache-inducing agents, but only the
      nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous
      infusions of the nitric oxide (NO) donor NTG induce a dose-dependent headache and
      dilatation of the temporal, radial and middle cerebral artery. NTG-induced
      headache, although less intense, resembles migraine in pain characteristics, but
      the accompanying symptoms are rarely present. Cephalic large arteries are dilated
      during migraine headache as well as during NTG headache. N-acetylcysteine
      enhances the formation of NO and potentiates NTG-induced headache, whereas
      mepyramine, a H1-antagonist capable of blocking histamine-induced headache, has
      no effect. Thus, the headache is dependent on NO or other steps in the NO
      cascade. The model is useful for pharmacological interventions and sumatriptan
      reduced the NTG-induced headache. The NTG model may be a valuable tool in the
      development of future migraine drugs.

PMID- 7585925
TI  - Assessment of peripheral vascular effects of antimigraine drugs in humans.
AB  - The vascular beds of the forearm and finger can be used to study the peripheral
      effects of antimigraine drugs under normal and pathologic circumstances. We have
      investigated the novel antimigraine drug sumatriptan, a selective agonist for
      5HT1 receptors. Its antimigraine effect may be attributed, at least in part, to
      constriction of cranial arteriovenous anastomoses (AVAs). In assessing the
      peripheral vascular effects of sumatriptan we used a forearm and finger blood
      flow model. Forearm blood flow (FBF) is mainly determined by resistance vessels,
      whereas finger blood flow (FiBF) mainly involves skin vessels, which contain many
      AVAs. Changes in FBF and FiBF can be assessed using venous occlusion
      plethysmography. Changes in AVA flow are determined by measuring the patency of
      the vascular beds of the forearm and hand to well-defined radiolabelled
      microspheres, which are injected into the brachial artery. We report the effects
      of sumatriptan on FBF, FiBF and AVA flow when administered into the brachial
      artery of healthy volunteers, and discuss the peripheral vascular effects of
      therapeutic doses of sumatriptan when given subcutaneously in migraine patients
      during and between attacks.

PMID- 7585926
TI  - The neuroendocrine challenge paradigm in headache research.
AB  - The neuroendocrine challenge paradigm provides a "window" on central
      neurotransmitter function in vivo. This strategy is based on the premise that the
      sensitivity of certain central receptors can be inferred from the magnitude of
      the hormonal response to specific pharmacologic probes. For example, the
      serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the
      release of cortisol and prolactin and induces migraine-like headaches. We have
      previously reported that the headache and cortisol responses to m-CPP are highly
      correlated, which may implicate a disturbance in central serotonergic
      neurotransmission in the pathogenesis of migraine. As pharmacologic probes with
      greater specificity for 5HT receptor subtypes become available, we may be able to
      elucidate these mechanisms with greater precision. The neuroendocrine challenge
      methodology is also applicable to the study of other neurotransmitter systems and
      other headache disorders.

PMID- 7585927
TI  - Changes of neuroendocrine axes in patients with menstrual migraine.
AB  - Menstrual migraine (MM) is a menstrually related disorder (MRD) characterized by
      several symptoms in common with premenstrual syndrome (PMS). It has been
      hypothesized that in both MM and PMS hormonal cyclicity could change the balance
      of neurotransmitters and neuromodulators like monoamine and opioid. In this
      article we analyze all the data collected by our group on the central opioid
      tonus and the adrenergic and serotonergic systems in patients affected by
      menstrual migraine.

PMID- 7585928
TI  - Clinical neurophysiology and neurotransmitters.
AB  - Clinical neurophysiology allows non-invasive assessment of neurotransmitter
      function in various regions of the central and peripheral nervous system. In this
      review, we describe examples of functional evaluation of neurotransmission at the
      neuromuscular junction, in some spinal interneurons and intracortical circuits as
      well as evaluation of pharmacological modulation of some electrophysiological
      tests. These investigations are carried out to help our understanding of the
      pathophysiology of brain diseases. Finally, we discuss possible relationships
      between electrophysiological tests (evoked/event-related potentials and
      exteroceptive suppression of temporalis muscle activity) and neurotransmitter
      function in headache.

PMID- 7585929
TI  - In vivo neuroreceptor imaging by SPECT in migraine.
AB  - In vivo imaging of neuroreceptor ligand binding in the human brain is a young
      discipline. In migraine patients only few studies on dopamine D2 receptor binding
      have been reported. Many potentially useful radiolabeled receptor ligands for
      SPECT investigations in humans are currently being treated in animal models.
      There are no reports on development of radiolabeled, specific 5HT1D receptor
      ligands, which would be of considerable interest in studies of migraine patients.
      The radiochemistry of receptor ligand development for SPECT is complex and
      expensive. However, once a suitable radiolabeled ligand has been developed, e.g.
      labeled with I-123 with a fairly long decay ratio, it can be made widely
      accessible to nuclear medical units. SPECT might even prove to be as powerful a
      tool as PET for quantification of neuroreceptor binding profiles. Quantification,
      though, is not a trivial problem and there is still a need for development of
      kinetic models that can be applied in the clinical setting, particularly for
      studies of acute conditions like a migraine attack.

PMID- 7585930
TI  - Is positron emission tomography a useful tool for studying migraine?
AB  - Despite the high prevalence of migraine in the population, the pathophysiology of
      this condition remains poorly understood. Vascular changes have been postulated.
      With positron emission tomography and various radiotracers, it is possible to
      have a non-invasive access to a number of parameters of interest in migraine
      research. These are presented and discussed in this article. PET has great
      potential for answering some basic questions concerning the physiological or
      biochemical changes that can occur during and between migraine attacks. Few
      studies have been published, however, probably because of (i) limitations
      inherent to the technique and (ii) problems in study design.

PMID- 7585931
TI  - Magnetic resonance spectroscopy in migraine.
AB  - 31-phosphorus Magnetic Resonance Spectroscopy (MRS) is a technique developed for
      the non-invasive study of energy metabolism in living subjects. It determines the
      concentrations of high and low energy phosphates in resting and activated
      conditions, and of intracellular pH. 31P-MRS has been applied to the study of
      migraine, both during and in between attacks. Intracellular brain pH remains
      unchanged during the migraine attack, suggesting that ischemia does not play a
      relevant role in the origin of the neurological signs. During and in-between
      attacks, migraineurs display abnormalities in energy metabolism of brain and
      muscle, consisting of reduced levels of phosphocreatine, reduced cellular-free
      energy and increased rate of ATP biosynthesis. We suggest that these
      abnormalities in energy metabolism predispose migraineurs to develop an attack
      under conditions of increased brain energy demand.

PMID- 7585933
TI  - Axon guidance molecules.

PMID- 7585935
TI  - Neuronal target recognition.

PMID- 7585934
TI  - Making the connection: cytoskeletal rearrangements during growth cone guidance.

PMID- 7585932
TI  - The bond between sisters.

PMID- 7585938
TI  - Divergent seven transmembrane receptors are candidate chemosensory receptors in
      C. elegans.
AB  - Using their senses of taste and smell, animals recognize a wide variety of
      chemicals. The nematode C. elegans has only fourteen types of chemosensory
      neurons, but it responds to dozens of chemicals, because each chemosensory neuron
      detects several stimuli. Here we describe over 40 highly divergent members of the
      G protein-coupled receptor family that could contribute to this functional
      diversity. Most of these candidate receptor genes are in clusters of two to nine
      similar genes. Eleven of fourteen tested genes appear to be expressed in small
      subsets of chemosensory neurons. A single type of chemosensory neuron can
      potentially express at least four different receptor genes. Some of these genes
      might encode receptors for water-soluble attractants, repellents, and pheromones.

PMID- 7585940
TI  - A role for a small stable RNA in modulating the activity of DNA-binding proteins.
AB  - The 10Sa RNA, encoded by the E. coli ssrA gene, appears to modulate action of
      some DNA-binding proteins. When ssrA is inactivated, lacZ expression from the lac
      operon, as well as galK from a gal operon fused to a phage lambda promoter, is
      reduced from that observed in bacteria wild-type for ssrA. These differences are
      not observed if the relevant repressor is inactive, suggesting that in the
      absence of 10Sa RNA binding of LacI and lambda cI repressors is enhanced. Gel
      mobility shifts show that 10Sa RNA binds these repressors and that an excess of
      10Sa RNA competes for binding of lambda cI with a DNA fragment containing the OR2
      repressor-binding sequence. Similar observations were made in studies of the E.
      coli LexA repressor and phage P22 C1 transcription activator proteins. These
      results suggest that direct interaction with 10Sa RNA may explain this modulation
      of protein-DNA interactions.

PMID- 7585941
TI  - Small peptides activate the latent sequence-specific DNA binding function of p53.
AB  - Normal cells contain p53 protein in a latent state that can be activated for
      sequence-specific transcription by low levels of UV radiation without an increase
      in protein levels. Microinjection of cells with an antibody specific to the C
      terminal negative regulatory domain can activate the function of p53 as a
      specific transcription factor in the absence of irradiation damage, suggesting
      that posttranslational modification of a negative regulatory domain in vivo is a
      rate-limiting step for p53 activation. Small peptides derived from the negative
      regulatory domain of p53 have been used as biochemical tools to distinguish
      between allosteric and steric mechanisms of negative regulation of p53 tetramer
      activity. Presented is the development of a highly specific peptide activation
      system that is consistent with an allosteric mechanism of negative regulation and
      that forms a precedent for the synthesis of novel low molecular mass modifiers of
      the p53 response.

PMID- 7585936
TI  - Synaptic structure and function: dynamic organization yields architectural
      precision.

PMID- 7585939
TI  - Extracellular signal protein triggering the proteolytic activation of a
      developmental transcription factor in B. subtilis.
AB  - We present biochemical evidence for an intercellular signal transduction pathway
      in B. subtilis. This pathway governs the conversion of the proprotein pro-sigma E
      to mature transcription factor sigma E. Proteolytic processing is mediated by the
      membrane protein SpollGA and is triggered by the inferred extracellular signal
      protein SpollR. A factor in conditioned medium from B. subtilis cells engineered
      to produce SpollR during growth triggered processing in protoplasts of B.
      subtilis cells that had been engineered to produce SpollGA and pro-sigma E. The
      factor was also detected in, and partially purified from, extracts of SpollR
      producing cells of E. coli. We speculate that SpollGA is both a receptor and a
      protease and the SpollR interacts with SpollGA on the outside of the cytoplasmic
      membrane, activating the intracellular protease domain of SpollGA.

PMID- 7585942
TI  - Mei-S332, a Drosophila protein required for sister-chromatid cohesion, can
      localize to meiotic centromere regions.
AB  - Mutations in the Drosophila mei-S332 gene cause premature separation of the
      sister chromatids in late anaphase of meiosis I. Therefore, the mei-S332 protein
      was postulated to hold the centromere regions of sister chromatids together until
      anaphase II. The mei-S332 gene encodes a novel 44 kDa protein. Mutations in mei
      S332 that differentially affect function in males or females map to distinct
      domains of the protein. A fusion of mei-S332 to the green fluorescent protein
      (GFP) is fully functional and localizes specifically to the centromere region of
      meiotic chromosomes. When sister chromatids separate at anaphase II, mei-S332-GFP
      disappears from the chromosomes, suggesting that the destruction or release of
      this protein is required for sister-chromatid separation.

PMID- 7585937
TI  - A novel family of genes encoding putative pheromone receptors in mammals.
AB  - In mammals, olfactory sensory perception is mediated by two anatomically and
      functionally distinct sensory organs: the main olfactory epithelium (MOE) and the
      vomeronasal organ (VNO). Pheromones activate the VNO and elicit a characteristic
      array of innate reproductive and social behaviors, along with dramatic
      neuroendocrine responses. Differential screening of cDNA libraries constructed
      from single sensory neurons from the rat VNO has led to the isolation of a family
      of about 30 putative receptor genes. Sequence analysis indicates that these genes
      comprise a novel family of seven transmembrane domain proteins unrelated to the
      receptors expressed in the MOE. Moreover, the expression of each member of the
      gene family is restricted to a small subpopulation of VNO neurons. These genes
      are likely to encode mammalian pheromone receptors.

PMID- 7585944
TI  - Overexpression of the neural growth-associated protein GAP-43 induces nerve
      sprouting in the adult nervous system of transgenic mice.
AB  - Regulation of neurite outgrowth and structural plasticity may involve the
      expression of intrinsic determinants controlling growth competence. We have
      tested this concept by targeting constitutive expression of the growth-associated
      protein GAP-43 to the neurons of adult transgenic mice. Such mice showed striking
      spontaneous nerve sprouting at the neuromuscular junction and in the terminal
      field of hippocampal mossy fibers. In control mice, these nerve fibers did not
      express GAP-43, and did not sprout spontaneously. Lesion-induced nerve sprouting
      and terminal arborization during reinnervation were greatly potentiated in GAP-43
      overexpressing mice. A mutant GAP-43 that cannot be phosphorylated by PKC had
      reduced sprout-promoting activity. The results establish GAP-43 as an intrinsic
      presynaptic determinant for neurite outgrowth and plasticity.

PMID- 7585943
TI  - Regulation of clathrin assembly and trimerization defined using recombinant
      triskelion hubs.
AB  - Clathrin polymerization into a polyhedral vesicle coat drives receptor sorting at
      cellular membranes during endocytosis and organelle biogenesis. To study clathrin
      self-assembly, we expressed the C-terminal third of the clathrin heavy chain in
      bacteria. The recombinant fragment trimerized, bound clathrin light chains, and
      morphologically resembled the hub domain of the triskelion-shaped clathrin
      molecule. Self-assembly of recombinant hubs demonstrated a regulatory role for
      clathrin light chains and for the distal portions of triskelion legs in clathrin
      coat formation. Deletion mutagenesis of the hub localized a domain mediating
      light chain binding and clathrin self-assembly and mapped a transferable
      trimerization domain. These studies define molecular interactions controlling
      clathrin self-assembly and establish a recombinant system for future analysis.

PMID- 7585945
TI  - Signals for death and survival: a two-step mechanism for cavitation in the
      vertebrate embryo.
AB  - Conversion of a solid primordium to a hollow tube of cells is a morphogenetic
      process used frequently during vertebrate embryogenesis. In the early mouse
      embryo, this process of cavitation transforms the solid embryonic ectoderm into a
      columnar epithelium surrounding a cavity. Using both established cell lines and
      normal embryos, we provide evidence that cavitation in the early mouse embryo is
      the result of the interplay of two signals, one from an outer layer of endoderm
      cells that acts over short distances to create a cavity by inducing apoptosis of
      the inner ectodermal cells, and the other a rescue signal mediated by contact
      with the basement membrane that is required for the survival of the columnar
      cells that line the cavity. This simple model provides a paradigm for
      investigating tube morphogenesis in diverse developmental settings.

PMID- 7585946
TI  - A dominant mutation in the Ikaros gene leads to rapid development of leukemia and
      lymphoma.
AB  - The Ikaros gene is essential for lymphoid lineage specification. As previously
      reported, mice homozygous for a mutation in the Ikaros DNA-binding domain fail to
      generate mature lymphocytes as well as their earliest described progenitors. In
      addition, our studies with mice heterozygous for this mutation establish the
      Ikaros gene as an essential regulator of T cell proliferation. Thymocytes display
      augmented TCR-mediated proliferative responses, and peripheral T cells are
      autoproliferative. A general lymphoproliferation precedes the T cell leukemia and
      lymphoma that rapidly develop in all heterozygotes. The first step toward
      leukemic transformation occurs within the maturing thymocyte population and is
      demarcated by clonal expansions and loss of the single Ikaros wild-type allele.
      From these studies, we propose that within developing and mature T lymphocytes,
      distinct thresholds of Ikaros activity are required to regulate proliferation. A
      decrease in Ikaros activity below the first threshold causes the rapid
      accumulation of T lymphoblasts, whereas a further decrease leads to neoplastic
      transformation.

PMID- 7585948
TI  - Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor
      neuron deficits at birth.
AB  - Ciliary neurotrophic factor (CNTF) supports motor neuron survival in vitro and in
      mouse models of motor neuron degeneration and was considered a candidate for the
      muscle-derived neurotrophic activity that regulates motor neuron survival during
      development. However, CNTF expression is very low in the embryo, and CNTF gene
      mutations in mice or human do not result in notable abnormalities of the
      developing nervous system. We have generated and directly compared mice
      containing null mutations in the genes encoding CNTF or its receptor (CNTFR
      alpha). Unlike mice lacking CNTF, mice lacking CNTFR alpha die perinatally and
      display severe motor neuron deficits. Thus, CNTFR alpha is critical for the
      developing nervous system, most likely by serving as a receptor for a second,
      developmentally important, CNTF-like ligand.

PMID- 7585949
TI  - A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P
      selectin binding.
AB  - P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like glycoprotein expressed
      on the surface of myeloid cells and serves as the high affinity counterreceptor
      for P-selectin. The PSGL-1-P-selectin interaction is calcium dependent and
      requires presentation of sialyl-Lewisx (sLex)-type structures on the O-linked
      glycans of PSGL-1. We report here the identification of a non-carbohydrate
      component of the binding determinant that is critical for high affinity binding
      to P-selectin. Located within the first 19 amino acids, this anionic polypeptide
      segment contains at least one sulfated tyrosine residue. We propose that this
      sulfotyrosine-containing segment of PSGL-1, in conjunction with sLex presented on
      O-linked glycans, constitutes the high affinity P-selectin-binding site.

PMID- 7585947
TI  - Multiple defects in the immune system of Lyn-deficient mice, culminating in
      autoimmune disease.
AB  - Mice homozygous for a disruption at the Lyn locus display abnormalities
      associated with the B lymphocyte lineage and in mast cell function. Despite
      reduced numbers of recirculating B lymphocytes, Lyn-/- mice are immunoglobulin M
      (IgM) hyperglobulinemic. Immune responses to T-independent and T-dependent
      antigens are affected. Lyn-/- mice fail to mediate an allergic response to IgE
      cross-linking, indicating that activation of LYN plays an indispensable role in
      Fc epsilon RI signaling. Lyn-/- mice have circulating autoreactive antibodies,
      and many show severe glomerulonephritis caused by the deposition of IgG immune
      complexes in the kidney, a pathology reminiscent of systemic lupus erythematosus.
      Collectively, these results implicate LYN as having an indispensable role in
      immunoglobulin-mediated signaling, particularly in establishing B cell tolerance.

PMID- 7585950
TI  - PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus
      at the PSGL-1 amino terminus.
AB  - P-selectin binding to neutrophils requires a specific protein, P-selectin
      glycoprotein ligand 1 (PSGL-1), as well as sialyl-Lewis X (sLex) glycan
      determinants. We have found that a short segment near the amino terminus of PSGL
      1 that contains a tyrosine sulfation consensus is essential for P-selectin
      adhesion and that addition of the amino-terminal segment to some but not all
      mucin-like molecules confers on those molecules the ability to bind P-selectin.
      PSGL-1 synthesized in the presence of sulfation inhibitors binds P-selectin
      weakly, and within the amino-terminal 20 residues, mutation of the tyrosines to
      phenylalanine abolishes binding. Rolling of HL-60 cells on P-selectin-coated
      coverslips is strongly attenuated by treatment of cells with an inhibitor of
      sulfation.

PMID- 7585952
TI  - Protein translocation across mitochondrial membranes: what a long, strange trip
      it is.

PMID- 7585951
TI  - Vacuolar biogenesis in yeast: sorting out the sorting proteins.

PMID- 7585953
TI  - Shedding light on the chloroplast protein import machinery.

PMID- 7585954
TI  - How proteins penetrate peroxisomes.

PMID- 7585957
TI  - A ribosomal DNA promoter replacing the promoter of a telomeric VSG gene
      expression site can be efficiently switched on and off in T. brucei.
AB  - Trypanosoma brucei survives in the mammalian blood-stream by regularly changing
      its variant surface glycoprotein (VSG) coat. The active VSG gene is located in a
      telomeric expression site, and coat switching occurs either by replacing the
      transcribed VSG gene or by changing the expression site that is active. To
      determine whether VSG expression site control requires promoter-specific
      sequences, we replaced the active VSG expression site promoter in bloodstream
      form T. brucei with a ribosomal DNA (rDNA) promoter. These transformants were
      fully infective in laboratory animals, and the rDNA promoter, which is normally
      constitutively active, was efficiently inactivated and reactivated in the context
      of the VSG gene expression site. As there is no sequence similarity between the
      VSG expression site promoter and the rDNA promoter, VSG expression site control
      does not involve sequences specific to the VSG expression site promoter. We
      conclude that an epigenetic mechanism, such as telomeric silencing, is involved
      in VSG expression site control in bloodstream-form T. brucei.

PMID- 7585956
TI  - The stabilization of repetitive tracts of DNA by variant repeats requires a
      functional DNA mismatch repair system.
AB  - Simple repetitive tracts of DNA are unstable in all organisms thus far examined.
      In the yeast S. cerevisiae, we show that a 51 bp poly(GT) tract alters length at
      a rate of about 10(-5) per cell division. Insertion of a single variant repeat
      (either AT or CT) into the middle of the poly(GT) tract results in 100-fold
      stabilization. This stabilization requires the DNA mismatch repair system.
      Alterations within tracts with variant repeats occur more frequently on one side
      of the interruption than on the other. The stabilizing effects of variant repeats
      and polarity of repeat alterations have also been observed in trinucleotide
      repeats associated with certain human diseases.

PMID- 7585958
TI  - A developmentally regulated position effect at a telomeric locus in Trypanosoma
      brucei.
AB  - Trypanosoma brucei undergoes antigenic variation in the mammalian host. This can
      be achieved by activation and inactivation of telomeric variant-specific surface
      glycoprotein genes (vsg). In procyclic (insect midgut stage) cells, Vsg is not
      expressed. The mechanisms that regulate transcription of vsg expression sites
      (ESs) are unknown. Here we demonstrate that transcription from three different
      promoters was repressed when they were inserted at a transcriptionally silent
      telomere-proximal locus in bloodstream-form cells. This position effect was
      stable and heritable. Only transcription from an ES promoter was repressed in
      procyclic cells. The observed position effect and the promoter-specific
      developmental regulation suggest that these phenomena reflect the mechanisms that
      regulate vsg expression.

PMID- 7585955
TI  - A group II intron RNA is a catalytic component of a DNA endonuclease involved in
      intron mobility.
AB  - The mobility (homing) of the yeast mitochondrial DNA group II intron al2 occurs
      via target DNA-primed reverse transcription at a double-strand break in the
      recipient DNA. Here, we show that the site-specific DNA endonuclease that makes
      the double-strand break is a ribonucleoprotein complex containing the al2-encoded
      reverse transcriptase protein and excised al2 RNA. Remarkably, the al2 RNA
      catalyzes cleavage of the sense strand of the recipient DNA, while the al2
      protein appears to cleave the antisense strand. The RNA-catalyzed sense strand
      cleavage occurs via a partial reverse splicing reaction in which the protein
      component stabilizes the active intron structure and appears to confer preference
      for DNA substrates. Our results demonstrate a biologically relevant ribozyme
      reaction with a substrate other than RNA.

PMID- 7585959
TI  - The multidomain structure of Orc1p reveals similarity to regulators of DNA
      replication and transcriptional silencing.
AB  - The origin recognition complex (ORC) is a six protein assembly that binds S.
      cerevisiae origins of replication and directs DNA replication throughout the
      genome and transcriptional silencing at the yeast mating-type loci. Here we
      report the cloning of the genes encoding the 120 kDa (ORC1), 62 kDa (ORC3), and
      56 kDa (ORC4) subunits of ORC and the reconstitution of the complete complex
      after expression of all six subunits in insect cells. Orc1p is related to Cdc6p
      and Cdc18p, which regulate DNA replication and mitosis, and to Sir3p, a regulator
      of transcriptional silencing. The N-terminal region of Orc1p is highly related to
      Sir3p, and studies of Orc1p/Sir3p chimeric proteins indicate that this domain is
      dedicated to the transcriptional silencing function of ORC.

PMID- 7585961
TI  - Mechanism of GroEL action: productive release of polypeptide from a sequestered
      position under GroES.
AB  - The chaperonin GroEL is a large, double-ring structure that, together with ATP
      and the cochaperonin GroES, assists protein folding in vivo. GroES forms an
      asymmetric complex with GroEL in which a single GroES ring binds one end of the
      GroEL cylinder. Cross-linking studies reveal that polypeptide binding occurs
      exclusively to the GroEL ring not occupied by GroES (trans). During the folding
      reaction, however, released GroES can rebind to the GroEL ring containing
      polypeptide (cis). The polypeptide is held tightly in a proteolytically protected
      environment in cis complexes, in the presence of ADP. Single turnover experiments
      with ornithine transcarbamylase reveal that polypeptide is productively released
      from the cis but not the trans complex. These observations suggest a two-step
      mechanism for GroEL-mediated folding. First, GroES displaces the polypeptide from
      its initial binding sites, sequestering it in the GroEL central cavity. Second,
      ATP hydrolysis induces release of GroES and productive release of polypeptide.

PMID- 7585960
TI  - HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix
      to the core domain of integrase.
AB  - The karyophilic properties of the viral matrix (MA) protein govern HIV nuclear
      import in nondividing cells such as macrophages. A critical regulator of this
      process is the C-terminal tyrosine phosphorylation of MA during virus maturation.
      Here, we reveal the mechanism of this phenomenon, by demonstrating that tyrosine
      phosphorylation induces the binding of MA to integrase (IN). This leads to the
      incorporation of MA molecules into virus cores, and subsequently into uncoated
      viral nucleoprotein complexes. A direct interaction between tyrosine
      phosphorylated MA and the central domain of IN can be demonstrated in vitro. It
      is blocked by phosphotyrosine, indicating that IN recognizes the phosphorylated C
      terminal residue of MA. These results explain how the karyophilic potential of MA
      is conferred to the HIV nucleoprotein complex.

PMID- 7585963
TI  - pop-1 encodes an HMG box protein required for the specification of a mesoderm
      precursor in early C. elegans embryos.
AB  - In C. elegans embryogenesis, the MS blastomere produces predominantly mesodermal
      cell types, while its sister E generates only endodermal tissue. We show that a
      maternal gene, pop-1, is essential for the specification of MS fate and that a
      mutation in pop-1 results in MS adopting an E fate. Previous studies have shown
      that the maternal gene skn-1 is required for both MS and E development and that
      skn-1 encodes a transcription factor. We show here that the pop-1 gene encodes a
      protein with an HMG box similar to the HMG boxes in the vertebrate lymphoid
      specific transcriptional regulators TCF-1 and LEF-1. We propose that POP-1 and
      SKN-1 function together in the early embryo to allow MS-specific differentiation.

PMID- 7585962
TI  - Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle.
AB  - The Hsc70-interacting protein Hip, a tetratricopeptide repeat protein,
      participates in the regulation of the eukaryotic 70 kDa heat shock cognate Hsc70.
      One Hip oligomer binds the ATPase domains of at least two Hsc70 molecules
      dependent on activation of the Hsc70 ATPase by Hsp40. While hydrolysis remains
      the rate-limiting step in the ATPase cycle, Hip stabilizes the ADP state of Hsc70
      that has a high affinity for substrate protein. Through its own chaperone
      activity, Hip may contribute to the interaction of Hsc70 with various target
      proteins. We propose a mechanism for the regulation of eukaryotic Hsc70 that is
      distinct from that of bacterial Hsp70. The Hsc70/Hsp40/Hip system is apparently
      independent of a GrpE-like nucleotide exchange factor.

PMID- 7585964
TI  - An FGF receptor signaling pathway is required for the normal cell migrations of
      the sex myoblasts in C. elegans hermaphrodites.
AB  - The sex myoblasts (SMs) in C. elegans hermaphrodites undergo anteriorly directed
      cell migrations that allow for the proper localization of the egg-laying muscles.
      These migrations are controlled in part by a signal emanating from gonadal cells
      that allows the SMs to be attracted to their precise final positions flanking the
      center of the gonad. Mutations in egl-15 alter the nature of the interaction
      between the gonad and the SMs, resulting in the posterior displacement of the
      SMs. Here we show that egl-15 encodes a receptor tyrosine kinase of the
      fibroblast growth factor receptor (FGFR) subfamily with multiple roles in
      development. Three genes were identified that behave genetically as activators or
      mediators of egl-15 activity. One of these genes, sem-5, encodes an adaptor
      molecule that transduces signals from a variety of receptor tyrosine kinases.
      Like egl-15 and sem-5, the other two genes may similarly act in FGFR signaling
      pathways in C. elegans.

PMID- 7585965
TI  - The identification of two novel ligands of the FGF receptor by a yeast screening
      method and their activity in Xenopus development.
AB  - We have developed a functional screen in yeast to identify ligands for receptor
      tyrosine kinases. Using this method, we cloned two Xenopus genes that activate
      the fibroblast growth factor (FGF) receptor. These encode novel secreted
      proteins, designated FRL1 and FRL2, distantly related to the epidermal growth
      factor and angiogenin/ribonuclease families, respectively. Both genes activate
      the FGF receptor in Xenopus oocytes as well as in yeast. Overexpression induces
      mesoderm and neural-specific genes in Xenopus explants; induction is blocked by a
      dominant negative inhibitor of the FGF receptor. FRL1 is broadly expressed during
      gastrulation and neurulation, while FRL2 is expressed principally in the axial
      mesoderm and brain at later stages. Our results indicate that despite their lack
      of similarity with FGF, FRL1 and FRL2 are ligands for the FGF receptor that play
      distinct roles in development.

PMID- 7585966
TI  - Induction of the LIM homeobox gene Lmx1 by WNT7a establishes dorsoventral pattern
      in the vertebrate limb.
AB  - During vertebrate limb development, the ectoderm directs the dorsoventral
      patterning of the underlying mesoderm. To define the molecular events involved in
      this process, we have analyzed the function of WNT7a, a secreted factor expressed
      in the dorsal ectoderm, and LMX1, a LIM homeodomain transcription factor
      expressed in the dorsal mesenchyme. Ectopic expression of Wnt7a is sufficient to
      induce and maintain Lmx1 expression in limb mesenchyme, both in vivo and in
      vitro. Ectopic expression of Lmx1 in the ventral mesenchyme is sufficient to
      generate double-dorsal limbs. Thus, the dorsalization of limb mesoderm appears to
      involve the WNT7a-mediated induction of Lmx1 in limb mesenchymal cells.

PMID- 7585967
TI  - Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by
      altering the mesodermal expression domains of Hox genes.
AB  - Cdx1 is expressed along the embryonic axis from day 7.5 postcoitum until day 12,
      by which time the anterior limit of expression has regressed from the hindbrain
      level to the forelimb bud region. To assign a functional role for Cdx1 in murine
      embryonic development, we have inactivated the gene via homologous recombination.
      Viable fertile homozygous mutant mice were obtained that show anterior homeotic
      transformations of vertebrae. These abnormalities were concomitant with posterior
      shifts of Hox gene expression domains in the somitic mesoderm. The presence of
      putative Cdx1-binding sites in Hox gene control regions as well as in vitro
      transactivation of Hoxa-7 indicates a direct regulation.

PMID- 7585968
TI  - The Bloom's syndrome gene product is homologous to RecQ helicases.
AB  - The Bloom's syndrome (BS) gene, BLM, plays an important role in the maintenance
      of genomic stability in somatic cells. A candidate for BLM was identified by
      direct selection of a cDNA derived from a 250 kb segment of the genome to which
      BLM had been assigned by somatic crossover point mapping. In this novel mapping
      method, cells were used from persons with BS that had undergone intragenic
      recombination within BLM. cDNA analysis of the candidate gene identified a 4437
      bp cDNA that encodes a 1417 amino acid peptide with homology to the RecQ
      helicases, a subfamily of DExH box-containing DNA and RNA helicases. The presence
      of chain-terminating mutations in the candidate gene in persons with BS proved
      that it was BLM.

PMID- 7585969
TI  - The pattern of cytokine gene expression induced in rat T cells specific for
      myelin basic protein depends on the type and quality of antigenic stimulus.
AB  - Rat T cells reactive against myelin basic protein (MBP) are exclusively, CD4+ CD8
      CD45RC-, inevitably produce abundant IFN-gamma, and appear to correspond to
      members of the Th1 CD4+ T cell subset characterized in mice. To ascertain the
      basis of the pathogenic activity of these cells, we studied their pattern of
      cytokine expression in response to activation by distinct TCR ligands. Using RT
      PCR and Northern blot assays to quantify cytokine gene production and cytokine
      production from intact cells, we show that (i) rat MBP-reactive T cells express
      IL-2, IFN-gamma, and TNF-alpha as well as IL-5 and IL-10; (ii) cytokine
      production is not an all or nothing phenomenon, but rather varies according to
      the type and dose of TCR ligand, leading to variation in the pattern of cytokine
      production, or dissociation between cytokine production and cell proliferation;
      and (iii) nonencephalitogenic T cells do not differ appreciably from their
      encephalitogenic counterparts in ability to produce major cytokines.

PMID- 7585971
TI  - Autogeneic but not allogeneic earthworm effector coelomocytes kill the mammalian
      tumor cell target K562.
AB  - Earthworm coelomocytes have been used as effector cells against the human tumor
      target, K562. To first assess the viability of effectors, incorporation of [3H]
      thymidine was tested and was higher in autogeneic (A<==A, self) than in
      allogeneic (A<==>B, nonself) coelomocytes. A<==>A showed significantly greater
      numbers in S, G2, or M phases than A<==>B coelomocytes. When A<==>A or A<==>B
      were cultured, no significant cell killing occurred in either, as measured in a 4
      hr 51Cr release assay. A<==>A but not A<==>B killed K562 target cells.
      Cytotoxicity was dependent upon membrane binding between small, electron-dense
      coelomocytes and targets; it was enhanced by adding PHA. The heat labile
      supernatant from A<==>A but not from A<==>B killed K562 targets after cultivation
      for 10 min at 22 degrees C, but not immediately after washing. Recognition of,
      binding to, and killing of foreign cells in a natural killer cell-like reaction
      may reflect natural immunity in earthworms.

PMID- 7585973
TI  - Characterization of a new antigen expressed by B and myeloid lineage cells
      identified by the monoclonal antibody LIP-6.
AB  - The LIP-6 MAb was produced against the undifferentiated cell line bh2-1 and
      recognizes an antigen expressed on all pre-B and B cell lines tested and some
      myeloid lineage lines. FACS analysis of normal tissues showed that LIP-6 is
      expressed on B lineage cells at all stages of differentiation, from bone marrow
      pre-B to plasma cells. T cells and thymocytes are LIP-6-, and splenic CD11b+
      cells are heterogeneous for LIP-6 expression. The LIP-6 MAb was shown to
      precipitate a major 75-kDa and a minor 85-kDa protein under reducing conditions
      and a large protein of > 240 kDa under nonreducing conditions. Removal of N
      linked sugars from the reduced lysates resulted in a single 65-kDa protein,
      suggesting that there is differential glycosylation of a single 65-kDa protein
      that forms disulfide-linked multimers. Finally, the LIP-6 antigen was shown not
      to be linked to the cell surface via a GPI linkage.

PMID- 7585972
TI  - Suppression of murine experimental autoimmune thyroiditis by oral administration
      of porcine thyroglobulin.
AB  - Experimental autoimmune thyroiditis (EAT) induced by the transfer of mouse
      thyroglobulin (MTg)-immunized spleen cells, activated in vitro with MTg, can be
      suppressed by oral administration of PTg to donor mice prior to immunization.
      Oral administration of 1 mg PTg five times over a 10-day period before
      immunization with MTg-LPS resulted in reduced EAT severity in recipient mice
      compared with recipients of cells from saline-fed immunized donors. MTg- or PTg
      specific proliferative responses were not decreased in PTg-fed donors and anti
      MTg antibody was not decreased in the donor mice fed 1 mg PTg. However, anti-MTg
      antibody production was markedly decreased in recipients of cells from PTg-fed
      donors compared with recipients of control cells. IgG1, IgG2A, and IgG2B anti-MTg
      antibody responses were all suppressed by PTg feeding suggesting that tolerance
      may be induced in both Th1 and Th2 cells. The more severe and histologically
      distinct granulomatous form of EAT was also suppressed by feeding PTg to donor
      mice. Studies are underway to determine the mechanism of oral tolerance in this
      model.

PMID- 7585974
TI  - Characterization of tumor-specific cytotoxic effector cells with a novel CD3-/Thy
      1+ phenotype.
AB  - The introduction and expression of allogeneic MHC class I genes in tumors can
      generate tumor-specific immunity which subsequently results in the regression of
      parental tumors. Immunization of naive (AKR/J x C57BL/6)F1 mice with H-2Kb
      transformed K36 tumor cells was found to render recipient mice immune to a
      subsequent challenge by parental K36 tumor cells. Two types of cytotoxic T
      effector cells were demonstrated in these immune mice. One of the cytotoxic
      effector cells generated against the K36 tumor cells is the conventional CD3+
      cells, and these account for approximately one-third of the total observed tumor
      specific cytotoxicity in vitro. The other cytotoxic effector cell generated
      following the immunization of (AKR/J x C57BL/6)F1 mice with the H-2Kb-transformed
      K36 cells had the CD3-/Thy-1+ phenotype, and accounted for the remaining two
      thirds of the observed tumor-specific cytotoxicity in vitro. These CD3-/Thy-1+
      cells can lyse parental K36 tumor cells in a tumor-specific fashion, and tumor
      specific immunity can be adoptively transferred to naive animals via the CD3-/Thy
      1+ cells. In contrast to CD3+ CTL, CD3-/Thy-1+ cells express CD45RBlow, Ly
      6Chigh, and HSA molecules. Although the CD3-/Thy-1+ cells can be activated in
      vitro by IL-2, TPA, and ionomycin, they cannot be propagated in vitro. The CD3
      /Thy-1+ cells undergo apoptosis following prolonged culture in vitro. At present,
      the exact mechanism(s) by which CD3-/Thy-1+ cells can mediate tumor-specific cell
      lysis in the absence of identifiable T cell receptor molecules is unknown;
      nevertheless, these data suggest the existence of a novel T cell type to combat
      tumors.

PMID- 7585970
TI  - Immunosuppression and induction of anergy by CTLA4Ig in vitro: effects on
      cellular and antibody responses of lymphocytes from rats with experimental
      autoimmune myasthenia gravis.
AB  - The pathogenic antibody response to acetylcholine receptor (AChR) in experimental
      autoimmune myasthenia gravis (EAMG) is T cell dependent. Therefore, it should be
      possible to design specific immunotherapeutic approaches to treat EAMG (and human
      MG) by interfering with AChR-specific helper T cells. Productive T cell
      activation by antigen requires at least two signals: one signal delivered through
      the T cell receptor by antigen and a second costimulatory signal delivered
      through the CD28 receptor via the B7 counterreceptor expressed on antigen
      presenting cells. Here we show that interference with the B7 costimulatory
      signal, using a soluble CD28 analogue, CTLA4Ig, resulted in a profound decrease
      in IL2 production and significantly decreased lymphoproliferative responses and
      antibody responses by primed lymph node cells from rats with EAMG, when
      stimulated with AChR in vitro. Nonclonal AChR-specific T cell lines, when
      stimulated with AChR in the presence of CTLA4Ig, were also inhibited in their
      ability to proliferate and to produce the cytokines IL2 and IFN-gamma. They
      remained deficient in their ability to produce IL2 when restimulated with AChR
      plus fresh antigen-presenting cells and showed variable inhibition of
      proliferation. The induction of hyporesponsiveness was accompanied by the
      expression of functional IL2 receptors, as shown by vigorous proliferative
      responses to addition of exogenous IL2. These results indicate that specific
      antigen stimulation in the presence of CTLA4Ig can induce certain features
      typical of anergy. CTLA4Ig provides a promising approach for the immunomodulation
      of MG and other antibody-mediated autoimmune diseases.

PMID- 7585975
TI  - Development of ulcerative colitis-associated anti-idiotype antibody using a novel
      monoclonal antibody against a colonic autoantigen.
AB  - Earlier studies have established reactivity of ulcerative colitis colon-bound IgG
      antibody with an autoantigen recognized by a novel monoclonal antibody, 7E12H12
      (IgM isotype). Purified 7E12H12-IgM was used to raise anti-idiotype antibody in
      the rabbit, and the presence of disease-specific idiotype(s) was evaluated in
      patients with ulcerative colitis. F(ab')2 fragments were prepared from serum-IgG
      of the rabbit immunized with 7E12H12-IgM and extensively absorbed against
      unrelated mouse IgM and purified serum IgG from 4 normal subjects. The reactivity
      of the absorbed F(ab')2 fragment was tested in an ELISA against the serum from 19
      patients with ulcerative colitis, 15 patients with Crohn's disease, and 10 normal
      subjects. The OD values with ulcerative colitis sera were significantly (P <
      0.0005) higher than those with Crohn's disease and normal sera. Blood serum from
      84% of patients with ulcerative colitis contains antibodies that are reactive to
      the F(ab')2 fragments of the immune rabbit serum-IgG. Further studies of the anti
      idiotype antibodies may elucidate autoimmune processes in ulcerative colitis and
      may have diagnostic and therapeutic values.

PMID- 7585976
TI  - Interleukin-12 is a costimulatory cytokine for leukemic CD3+ large granular
      lymphocytes.
AB  - The activation signals leading to proliferation of leukemic CD3+ large granular
      lymphocytes (LGL) are incompletely understood. In this study, the role of
      recombinant human interleukin-12 (rhIL-12) alone or in combination with other
      activation signals was studied in vitro. Anti-CD3 monoclonal antibody (MoAb)
      alone caused marked stimulation of peripheral blood mononuclear cells (PBMC) from
      three CD3+ LGL leukemic patients, whereas rhIL-12 alone had less effect as
      measured in a [3H]thymidine incorporation assay. The combination signals of anti
      CD3 MoAb and rhIL-12 produced a proliferative response greater than anti-CD3 MoAb
      alone or rhIL-12 alone. Leukemic LGL, purified by CD8+ affinity chromatography,
      showed similar proliferative responses as PBMC from LGL leukemic patients,
      suggesting that the observed effect was indeed due to direct stimulation of
      leukemic LGL. Radiolabeled IL-12 binding studies demonstrated that anti-CD3 MoAb
      upregulated the number of IL-12 receptors per cell on PBMC from these patients.
      Neutralizing antibody to rhIL-12 partially blocked the proliferative response to
      anti-CD3 MoAb suggesting involvement of IL-12 in the pathway of activation of
      leukemic LGL via stimulation of the T cell receptor (TCR) (mimicking activation
      by antigen). These results show that IL-12 acts as a costimulatory cytokine for
      proliferation of leukemic LGL activated through the TCR in vitro.

PMID- 7585977
TI  - Phorbol ester-induced upregulation of polymorphonuclear leukocyte P-selectin
      ligand expression.
AB  - Proinflammatory stimuli cause the vascular endothelium to express P-selectin that
      tethers leukocytes by binding surface glycoprotein carbohydrate. While the
      activation of polymorphonuclear leukocytes (PMN) is associated with upregulation
      of the beta 2-integrins, there is little known about the regulated expression of
      the ligand for the endothelial P-selectin. We have used a soluble chimeric P
      selectin protein as a probe for the expression of ligand on the surface of the
      PMN. Treatment with phorbol ester for more than 20 min stimulated P-selectin
      ligand expression. The upregulation of beta 2-integrin expression was affected in
      a similar manner. The mechanism of selectin ligand upregulation did not involve
      de novo protein synthesis, and may involve translocation of membranes containing
      performed intracellular ligand. C5a, which is generated in response to complement
      activation in vivo, also stimulated selectin ligand upregulation. Degranulation
      induced by nigericin increased ligand expression, and TNF-alpha treatment
      resulted in a modest upregulation.

PMID- 7585978
TI  - A role for microfilaments but not microtubules in processing soluble antigens.
AB  - Ag processing involves multiple intracellular membrane transport events required
      for delivery of Ag to degradative compartments in the endocytic pathway of
      antigen-presenting cells (APC) and transport of newly synthesized class II MHC
      proteins to compartments where peptide loading occurs. Movement and distribution
      of various subcellular vesicles have been shown to involve elements of the
      cytoskeletal network. We have examined the role of microtubules and
      microfilaments in Ag processing and presentation by B lymphoblastoid cells.
      Experiments with nocodazole or colchicine, drugs that disrupt the microtubule
      network, demonstrate that intact microtubules are not required for efficient
      processing of soluble Ag in these cells. Cytochalasins, which disrupt actin
      microfilaments, are observed to partially inhibit processing of soluble Ag.
      Inhibition is reversible and dependent on both the dose of drug and length of
      exposure. Control experiments demonstrate that the effect does not result from
      drug toxicity or decreased Ag uptake. Treatment of APC with cytochalasin B does
      not block delivery of internalized protein to dense lysosomes. However, the
      ability of the cells to catabolize internalized protein is partially inhibited.
      Our results suggest that microfilament-dependent, but not microtubule-dependent,
      vesicular transport may be required for efficient Ag processing in B
      lymphoblastoid cells.

PMID- 7585979
TI  - Differential binding of two chicken beta-galactoside-specific lectins to
      homologous lymphocyte subpopulations and evidence for inhibitor activity of the
      dimeric lectin on stimulated T cells.
AB  - Plant lectins can be potent modulators of vertebrate immune functions.
      Biochemical characterization of lectins from animal tissues enables the
      determination of whether these endogenous activities display a comparable
      immunological potency. Focusing on chicken beta-galactoside-binding lectins, the
      monomeric intestinal (CL-14) and the dimeric liver lectin (CL-16) were purified
      and the lack of cross-contamination was ascertained. In very close agreement with
      the molecular masses of 14,974 and 14,976 calculated on the basis of the
      available sequence data (Y. Sakakura et al., J. Biol. Chem. 265, 21573-21579,
      1990), electrospray mass spectrometric analysis yielded values of 14,969 (CL-14)
      and 14,972 (CL-16), the reasons for the deviation in gel electrophoretic behavior
      being unclear. Solid-phase assays with immobilized lactosylated poly-L-lysine
      demonstrated a comparatively lower affinity and higher extent of binding at
      saturation for the monomeric lectin than for the dimeric protein, whose
      properties were similar to those of an immunomodulatory plant lectin. Flow
      cytometry revealed homogeneous and strong binding of the dimeric lectin within
      the chicken peripheral blood lymphocyte population, whereas the monomeric lectin
      stained two subpopulations at different intensities. Two-color flow cytometry
      disclosed preferential binding of this lectin to B cells. When a B cell line was
      employed for determination of affinity constants and extents of binding at
      saturation, qualitatively comparable parameters to those for the solid-phase
      assays were obtained. The similar profile of lectin-binding glycoproteins in
      blots of cellular extracts underscored that accessibility to ligands, not
      qualitatively different ligand display, may explain the differences for the cell
      line. At up to a concentration of 10 micrograms/ml of the lectins no stimulation
      of [3H]thymidine incorporation was seen for blood and spleen cell populations.
      However, the dimeric lectin reduced stimulation of cells that were responsive to
      an anti-TcR2 antibody. Thus, this lectin can apparently exhibit inhibitory
      activity to this kind of T cell activation in vitro.

PMID- 7585981
TI  - The role of integrins in adhesion of decidual NK cells to extracellular matrix
      and decidual stromal cells.
AB  - At the time of implantation, the decidua is infiltrated by a unique population of
      NK cells with large granular lymphocyte morphology, which are thought to
      influence placental trophoblast invasion and differentiation. The mechanisms used
      by these cells to migrate within decidua are not known, but in other biological
      processes such as wound healing and tumor invasion cell-matrix interactions are
      important. These interactions are mediated by specific receptors, mostly
      belonging to the family of integrins. Decidual NK cells are observed to bind to
      type IV collagen and fibronectin, but not to laminin. Adhesion to collagen was
      inhibited with an anti-alpha 1 integrin subunit mAb, whereas adhesion to
      fibronectin was blocked with anti-alpha 4, -alpha 5, and -beta 1 integrin subunit
      mAbs. Binding of decidual NK cells to decidual stromal cells was partially
      blocked with mAbs to the alpha 4 and alpha 5 integrin subunits. These results
      provide insight into the possible mechanisms utilized by decidual NK cells for
      migration and retention within the pregnant uterine mucosa.

PMID- 7585980
TI  - Evidence for protein tyrosine kinase involvement in CD6-induced T cell
      proliferation.
AB  - Several studies have demonstrated that addition of soluble anti-CD6 mAbs to 12-O
      tetradecanoylphorbol 13-acetate (TPA)-treated naive T cells can induce cell
      proliferation. We showed in the present study that cell proliferation in TPA
      treated T cell cultures can be enhanced several fold when the anti-CD6 mAbs are
      either immobilized or crosslinked with rabbit anti-mouse immunoglobulins (RAM
      Ig). Using a src family protein tyrosine kinase (PTK) inhibitor, herbimycin A,
      the cell proliferation induced by the anti-CD6 mAb, IOR-T1, in TPA-treated T
      cells were effectively abolished. Analysis of the cellular proteins in these
      cells after crosslinking the CD6 receptor with IOR-T1 (followed by RAM Ig) in the
      presence of TPA resulted in an increased level of tyrosine phosphorylation.
      Pretreatment of native T cells with herbimycin A (0.5 and 1 microgram/ml) for 18
      hr completely inhibited the tyrosine phosphorylation on cellular substrates in T
      cell cultures stimulated with IOR-T1/RAM Ig and TPA. Similar concentrations of
      herbimycin A also inhibited the increase in IL-2 mRNA expression and cell
      proliferation in T cell cultures after IOR-T1/RAM Ig and TPA treatment.
      Furthermore, the increase in cytosolic free Ca2+ concentration in naive T cells
      after crosslinking of the CD6 receptor with IOR-T1/RAM Ig was also inhibited by
      herbimycin A. Taken together, our results suggest that CD6-mediated T cell
      proliferation is IL-2 dependent, and involves tyrosine kinase activity which is
      strictly dependent on protein kinase C activation.

PMID- 7585982
TI  - A subset of splenic macrophages process and present native antigen to naive
      antigen-specific CD4+ T-cells from mice transgenic for an alpha beta T-cell
      receptor.
AB  - The progeny of individual macrophage precursors from mouse spleen were examined
      for their ability to constitutively process and present native pigeon cytochrome
      c or a peptide fragment of this antigen to naive CD4+ T-cells from mice
      transgenic for a V alpha 11/V beta 3 TCR that recognizes an epitope in the
      antigen fragment. The results show that constitutive Ag processing and
      presentation is a stable characteristic restricted to the progeny of
      approximately 20% of splenic macrophage precursors. This property does not appear
      to be randomly acquired, but to reflect the ability of certain macrophages to
      produce IL-12.

PMID- 7585983
TI  - Subcellular location of neutrophil opsonic receptors is altered by exogenous
      reactive oxygen species.
AB  - The effect of exposure of PMN to extracellular oxidants on the PMN oxidative
      burst on the subcellular location of CD64 (Fc gamma RI), CD32w (Fc gamma RII),
      CD16 (Fc gamma RIII), CD35 (complement receptor 1), and CD11b/CD18 (complement
      receptor 5) was studied. Incubation of PMN with glucose/glucose oxidase resulted
      in an intracellular shift in Fc gamma receptors from secretory vesicles to plasma
      membrane fractions while reducing complement receptor expression in plasma
      membrane fractions. Incubation of PMN with xanthine/xanthine oxidase resulted in
      an intracellular shift in Fc gamma receptors from specific granules to secretory
      vesicles. Incubation of PMN with xanthine/xanthine oxidase resulted in an
      intracellular shift from secretory vesicles to plasma membrane fractions for CD35
      and from secretory vesicles and specific granules to plasma membrane fractions
      for CD11b/CD18. The effects of glucose/glucose oxidase and xanthine/xanthine
      oxidase on receptor redistribution were blocked by catalase and catalase and
      superoxide dismutase, respectively. Cytoskeleton stabilization with phalloidin
      and Taxol blocked the effect of glucose/glucose oxidase and xanthine/xanthine
      oxidase on Fc gamma and complement receptor relocation. Both H-7 and
      staurosporine abrogated the effect of glucose/glucose oxidase and
      xanthine/xanthine oxidase on Fc gamma receptor relocation, while genistein
      abrogated the effect of glucose/glucose oxidase and xanthine/xanthine oxidase on
      complement receptor relocation. Increases in CD64, CD32w, CD16, CD35, and
      CD11b/CD18 expression associated with plasma membrane fractions corresponded to
      functional increases in monomeric IgG binding, E-IV.3, (sheep erythrocyte
      opsonized with monoclonal antibody IV.3 directed against CD32w) E-Con A, EC3b,
      and EC3bi rosetting. These studies indicate that exposure of PMN to extracellular
      oxidants does not occur as an isolated event but results in a coordinated
      subcellular relocation of opsonic receptors which corresponds to changes in PMN
      function.

PMID- 7585985
TI  - High-density presentation of an immunodominant minimal peptide on B cells is MHC
      linked to Th1-like immunity.
AB  - Ligand-directed differences in the amount of peptide presented on a specific APC
      subset could influence the functional outcome of any given immune response. We
      have investigated this issue with a biochemically determined immunodominant
      peptide that is presented at a higher density on the APC of Th1 responders (I-As
      genotypes) than on the APC of Th2 responders (I-Ab genotypes). MHC-linked high
      peptide density is expressed on B lymphocytes, predominantly those that bear the
      B7-2 activation marker/costimulatory ligand. We further investigated the role of
      I-As-specific polymorphism with transfected cells bearing an R-->Q change at
      position-70 of A beta (found only in the I-As allele). Strikingly, I-Ab
      restricted Th1 and Th2 clones proliferate at a peptide dose 10- to 100-fold lower
      than wild-type on transfected fibroblasts bearing this single s-like substitution
      in A beta b. Moreover, the shift in the clone dose response is sensitive to the
      peptide's C-terminus, as is MHC-linked Th1-like immunity to this peptide in vivo.
      Together, these data suggest that ligand-density can dictate Th1/Th2 selection
      via a single MHC polymorphism that determines the level of peptide presented to a
      given TCR on activated B cells.

PMID- 7585987
TI  - Production of polyclonal and monoclonal antibodies against hyphae from arbuscular
      mycorrhizal fungi.
AB  - Polyclonal and monoclonal antibodies were produced against hyphae of the
      arbuscular mycorrhizal fungus Glomus monosporum. The polyclonal antibodies (pAbs)
      were raised in a rabbit by immunizing with hyphae. They were tested for their
      specificity by a dot-immunoblot assay (DIBA). After the third immunization, a
      distinct difference in the signal strength was observed between the antisera and
      the preimmune serum. The pAbs showed cross-reactions to a number of fungal
      species, both mycorrhizal and other. For the production of monoclonal antibodies
      (mAbs), mice were immunized intraperitoneally with hyphae. The resulting
      hybridoma cell culture supernatants were tested by an indirect immunolabeling
      procedure. For this purpose the hyphae were immobilized on silane-coated
      microscopic slides. The mAb 8A7 reacted with hyphae from all Glomus isolates
      tested so far. Cross-reactivities were not observed with hyphae from fungi of the
      family Acaulosporaceae, phytopathogenic fungi tested so far, or from spores from
      Glomus species.

PMID- 7585984
TI  - B cell lines from a subset of patients with common variable immunodeficiency
      undergo enhanced apoptosis associated with an increased display of CD95 (Apo
      1/fas), diminished CD38 expression, and decreased IgG and IgA production.
AB  - Investigation of common variable immunodeficiency (CVI) is hampered by lack of a
      suitable in vitro models. We have developed EBV-transformed B lymphoblastoid cell
      lines from a selected subset of CVI patients and characterized them for
      phenotypic and functional properties that provide evidence for their
      representation of the CVI disease state. B cell lines from the patients expressed
      increased levels of sIgM and reduced levels of sIgD and sIgG. Essentially none of
      the CVI-derived B cell lines produced IgG and IgA while all produced IgM, in
      contrast to normal B cell lines that produced large amounts of IgG and IgM and
      detectable levels of IgA. Expression of CD95 (fas/Apo-1), a molecule that can
      induce apoptosis, was increased on the CVI B cell lines while CD38, a novel
      signaling molecule whose stimulation may prevent apoptosis, showed reduced
      expression. The B cell lines from the CVI patients exhibit increased apoptosis in
      vitro spontaneously, in response to anti-CD95 mAb and to X-irradiation. These
      phenotypic and functional changes are similar to findings on freshly derived B
      cells from the patients. EBV-derived B cell lines from patients with hyper-IgM
      immunodeficiency and X-linked agammaglobulinemia did not demonstrate increased
      CD95 expression or enhanced apoptosis. Thus the EBV-derived B cell lines from our
      selected CVI patients manifest many characteristics of the patients' fresh cells
      and may provide critical reagents for the further elucidation of the nature of
      the B cell dysfunction in the selected subset of CVI patients.

PMID- 7585986
TI  - Differential regulatory effects of cAMP-elevating agents on human normal and
      neoplastic B cell functional response following ligation of surface
      immunoglobulin and CD40.
AB  - The B cell response to ligation of surface immunoglobulin (sIg) and CD40 is
      dependent on the stage of cellular differentiation of the population studied.
      Cross-linking sIg promotes proliferation of follicular mantle (FM) B cells,
      rescues germinal center (GC) B cells from spontaneous apoptosis but induces
      apoptosis in susceptible Burkitt lymphoma (BL) B cells; signals transduced
      through CD40 induce resting FM B cells to enter cell cycle while promoting GC and
      BL B cell survival. This study investigates whether the 3', 5'-cyclic adenosine
      monophosphate (cAMP)-dependent second-messenger pathway plays a role in the
      regulation of these sIg- and CD40-promoted B cell responses, using prostaglandin
      E2 (PGE2) and forskolin to artificially increase intracellular levels of cAMP.
      The Epstein-Barr virus (EBV)-genome-negative BL B cell line Ramos is susceptible
      to growth arrest and apoptosis triggered by calcium ionophore, anti-IgM and
      forskolin but not by PGE2; forskolin does not affect the outcome of anti-IgM
      treatment. Anti-CD40 rescues Ramos-BL B cells from ionophore- and anti-IgM
      triggered but not forskolin-triggered growth arrest and apoptosis; moreover,
      forskolin and anti-CD40 act additively and independently for enhanced growth
      inhibition. By contrast, both forskolin and PGE2 potentiate the proliferative
      response of FM B cells cultured with anti-Ig and anti-CD40 together but not
      individually. Forskolin and PGE2 fail to affect the spontaneous apoptosis and
      anti-Ig- and anti-CD40-promoted survival of GC B cells. Thus, the cAMP-dependent
      second messenger pathway can differentially influence the BL, FM, and GC B cell
      functional response to signals transduced through sIg and CD40.

PMID- 7585988
TI  - Focal adhesion proteins associated with apical stress fibers of human
      fibroblasts.
AB  - Human fibroblasts stained with fluorescently labeled phalloidin revealed many
      stress fibers within the apical cytoplasm in addition to those located along the
      basal plasma membrane and associated with focal adhesions. The staining patterns
      of these apical stress fibers with fluorescent phalloidin, anti-alpha-actinin,
      and antimyosin were identical to those of the basal stress fibers, suggesting the
      same macromolecular organization for both types of stress fibers. There were two
      types of apical stress fibers that clearly interacted with the apical plasma
      membrane, those extending between the basal and the apical plasma membrane and
      those having both ends on the basal membrane forming arches whose top interacted
      with the apical plasma membrane. By electron microscopy, we observed that apical
      stress fibers were associated with the apical plasma membrane via electron-dense
      plaques reminiscent of the focal adhesion. Since several proteins have been
      specifically localized to the focal adhesion site, we examined whether they were
      also present at the apical stress fiber-membrane association site by using
      immunocytochemical methods and image reconstruction techniques. We found that
      vinculin, talin, paxillin, a fibronectin receptor protein, several integrin
      subunits including beta 1, fibronectin, and proteins with phosphorylated tyrosine
      were also components of the apical plaque. These observations indicate that
      apical stress fibers are attached to the plasma membrane by using principally the
      same molecular assembly as the focal adhesion associated with the basal stress
      fiber. We suggest that the complex molecular organization of the focal adhesion
      is not demanded by cell adhesion, but rather it is needed for anchoring stress
      fibers to the plasma membrane. Apical plaques did not stain with the anti
      integrin alpha v subunit or anti-focal adhesion associated kinase (FAK), although
      these antibodies stained focal adhesions. These results suggest that the apical
      stress fiber-membrane contact has some important functions different from those
      of the focal adhesion.

PMID- 7585989
TI  - Exogenous gelsolin binds to sarcomeric thin filaments without severing.
AB  - We have investigated the binding of gelsolin to thin myofilaments in situ and
      their stability against severing. Differentiated myotubes from chicken skeletal
      muscle containing cross-striated myofibrils were permeabilized with Triton X-100
      and incubated with gelsolin. Immunofluorescence microscopy localized both
      endogenous and exogenous gelsolin in the I-Z-I-regions of the sarcomers. The
      staining pattern suggested a binding of the exogenous gelsolin along the entire
      length of the thin filaments. This binding was Ca2+ dependent, but gelsolin was
      not removed after subsequent addition of EGTA. The fluorescence staining for
      actin remained unchanged after gelsolin incubation, indicating that thin
      filaments in cross-striated myofibrils were resistant to the severing action of
      gelsolin, in contrast to the microfilaments in stress fibers. After extraction of
      the permeabilized cells with high ionic strength to remove tropomyosin and
      myosin, gelsolin still bound along the entire thin filament and the actin pattern
      also remained unchanged. After Triton X-100 permeabilization and high ionic
      strength extraction, the giant protein nebulin was found to be still present as a
      myofibrillar component. Gelsolin treatment after high salt extraction affected
      neither actin nor nebulin in the thin filaments. We therefore conclude that
      nebulin confers the gelsolin resistance to the sarcomeric actin filaments.

PMID- 7585990
TI  - Novel mode of hyper-oscillation in the paralyzed axoneme of a Chlamydomonas
      mutant lacking the central-pair microtubules.
AB  - The flagellar axoneme of the mutant pf18 lacking the central pair does not beat,
      but undergoes a nanometer-scale, high-frequency oscillation (hyper-oscillation)
      in the presence of ATP [Yagi et al., 1994: Cell Motil. Cytoskeleton 29:177-185].
      The present study demonstrates that the amplitude of the hyper-oscillation
      increases significantly in the simultaneous presence of ATP and ADP. In addition,
      the hyper-oscillation under these conditions sometimes takes on an exceptionally
      simple asymmetric pattern, in which the maximal shearing velocity exceeds 50
      microns/sec, much higher than the maximal velocity of ordinary dynein-microtubule
      sliding. The asymmetric oscillation thus appears to be at least partly driven by
      an internal elastic force. Its amplitude suggests that the axoneme has an elastic
      component that can be stretched by as long as 0.1 micron. Analyses of the
      asymmetric pattern further suggests that the axonemal dyneins have a tendency to
      attach to and detach from the doublets cooperatively and that the mechanochemical
      cycle of dynein has an inherent refractory period of about 2 msec, during which
      dynein cannot interact with microtubules.

PMID- 7585991
TI  - Focal adhesion formation is associated with secretion of allergic mediators.
AB  - Adherence of cells to the extracellular matrix via focal adhesions is known to
      modulate many cellular functions. However, the role of focal adhesions in the
      regulation of secretion is unclear. To examine this we have used the RBL-2H3 rat
      mast cell line, in which we and others have observed cytoskeletal rearrangements
      and increased cell spreading during secretion. All activators of secretion
      examined, whether acting specifically through or bypassing the IgE-receptor,
      induced the assembly of focal adhesions, as defined by the localization of
      vinculin and talin. The extent of focal adhesion formation correlated with the
      extent of secretion and the time course of secretion also correlated with that of
      the assembly of focal adhesions. To examine the mechanism by which focal adhesion
      formation occurred, the protein kinase C inhibitor bisindolylmaleimide was used.
      Bisindolylmaleimide caused complete inhibition of both secretion and focal
      adhesion formation induced by antigen or the calcium ionophore A23187. Although
      PMA did not induce secretion, it induced focal adhesion assembly which was
      inhibited by bisindolylmaleimide. The inhibitor had no effect on secretion or
      focal adhesion formation induced by the ATP analogue, ATP gamma S in
      permeabilized cells, indicating ATP gamma S acts after the activation of protein
      kinase C in the secretory pathway. These data provide novel evidence that the
      formation of focal adhesions may have a role in the process of secretion from
      mast cells.

PMID- 7585992
TI  - Traction forces in locomoting cells.
AB  - A means of determining quantitative maps of the tractions exerted by locomoting
      cells on a substratum has been developed. This method is similar to the Harris
      silicone substratum assay [Harris et al., 1980: Science 208:177-179], but uses an
      improved non-wrinkling film that deforms more predictably in response to traction
      forces. The method also utilizes a mathematical analysis of rubber deformation to
      produce the final map of the distribution of tractions. The resulting maps
      consistently showed that fish keratocytes exert a steady-state "pinching" on the
      substratum, perpendicular to the cell's direction of locomotion. No significant
      rearward tractions were detected at or near the front edge of the cell. Likewise,
      no significant forward tractions associated with peeling of adhesions were found
      at the back of the cell. A second assay uses deflection of a lightly attached
      glass microneedle to measure the total force exerted by locomoting cells. Forces
      of approximately 4.5 x 10(-3) dyn were required to "stall" locomoting
      keratocytes. The implications of these findings for cell movement are discussed.

PMID- 7585994
TI  - A new way to look at an old condition.

PMID- 7585996
TI  - Occlusal neurotic or neuroticongenic occlusion.

PMID- 7585993
TI  - In Ascaris sperm pseudopods, MSP fibers move proximally at a constant rate
      regardless of the forward rate of cellular translocation.
AB  - Computer-assisted methods have been employed to obtain a high resolution
      description of pseudopod expansion, cellular translocation, and the subcellular
      dynamics of MSP fiber complexes in the motile sperm of the nematode Ascaris suum.
      Although Ascaris sperm translocating in a straight line or along a curved path do
      not retract their pseudopod or significantly alter pseudopod shape, they move in
      a cyclic fashion, with an average period between velocity peaks of 0.35 +/- 0.05
      min, which is independent of the forward velocity of sperm translocation.
      Expansion is confined to a central zone at the distal edge of the pseudopod for
      sperm translocating in a straight line and to a left-handed or right-handed
      lateral zone in the direction of turning, for sperm translocating along a curved
      path. For cells translocating in a straight line, the branch points and kinks of
      MSP fiber complexes move in a retrograde direction in relation to the substratum
      at an average velocity of 11 microns per min which is independent of the forward
      velocity of sperm translocation. The distal (anterior) end of a fiber complex,
      however, moves distally at the speed of sperm translocation when it emanates from
      the expansion zone, but when it is displaced to a nonexpanding surface of the
      pseudopod, it stops moving distally. When a cell is anchored to the substratum
      and is, therefore, nonmotile, the velocity of fiber complexes moving in a
      retrograde direction doubles. The unique aspects of pseudopod and MSP fiber
      complex dynamics in Ascaris are compared to the dynamics of pseudopod formation
      and actin filament dynamics in traditional actin-based amoeboid cells, and the
      treadmill model for MSP polymerization is reassessed in light of the discovery
      that fiber complex branch points move proximally (posteriorly) at a fixed rate.

PMID- 7585995
TI  - Submentovertex radiology: cephalometric considerations in temporomandibular
      dysfunction.
AB  - Controversy exists in the literature concerning the association between the
      radiographic and the clinical features of the temporomandibular dysfunction
      (TMD). Hence, this study reinvestigated possible correlations between
      radiographically detected asymmetries and the clinical signs and symptoms of TMD.
      Complete clinical and radiographic records were gathered from 52 patients
      sequentially referred for corrected angle tomographs of the temporomandibular
      joint (TMJ). Measurements from submentovertex (SMV), lateral and posterior
      anterior (PA) cephalographs and corrected angle parasagittal tomographs and
      recorded clinical signs and symptoms of TMD were the data inputs. Significant
      findings were as follows: a) as the discrepancy in the posterior condyle to
      pogonion measurement increased, the pogonion and both maxillary and mandibular
      incisors shifted laterally towards the shorter side; b) as the ANB angle
      increased, so did the difference in condylar angle measurements between the two
      condyles; c) the side with the larger condylar angle was positioned forward on
      the SMV; and d) a perpendicular bisector (Marmary's Centerline) of the line drawn
      between the right and left foramen spinosum was found to be a reliable baseline
      reference for SMV analyses. No statistically significant relation was found
      linking specific signs and symptoms of TMD to maxillofacial asymmetries recorded
      on SMV, lateral or PA cephalographs. None of the radiographic signs studied were
      found to be good predictors of specific signs and symptoms in TMD.

PMID- 7585997
TI  - A modified extraoral technique of mandibular manipulation in disk displacement
      without reduction.
AB  - A main reason for failure when manipulating a mandible in disk displacement
      without reduction is a lack of coordination, because of a sudden resistance on
      the patient's part when fingers are placed in his mouth. This work describes a
      new extraoral manipulation technique that avoids this problem. Basically, this
      technique involves three stages. In stage one, the patient performs rhythmic left
      and right sideways movements unassisted; in stage two, gentle finger pressure is
      applied by the clinician on the external aspect of the mandible in the same
      direction as the patient's movements; and in stage three, the mandible is
      forcefully pulled towards the non-lesion side in strict concomitance with the
      mandibular movement of the patient towards the same side (Figure 1). Usually a
      splint is then placed intra-orally for three-to-five months, and physical therapy
      and exercises are prescribed as needed. The technique described improves the rate
      of success in the management of permanently displaced disks, so that indication
      for surgery may drop to close to zero. The chronicity of the lesion does not seem
      to be an exclusion criteria, provided the lesion still has the characteristics of
      a disk displacement with reduction and no pseudodisk or degeneration has arisen.
      Treatment success is confirmed by the improvement of free mandibular and
      masticatory movements and by the absence of pain.

PMID- 7585998
TI  - Clinical analysis of mid-laser versus placebo treatment of arthralgic TMJ
      degenerative joints.
AB  - Laser therapy has been found effective in the management of pain associated with
      rheumatoid and degenerative joint arthritis and disease. The efficacy of mid
      laser therapy has been tested specifically on patients with degenerative joint
      disease (DJD) involving the temporomandibular joint (TMJ). The following
      controlled clinical study was designed to test the efficacy of mid-laser therapy
      to placebo therapy in the reduction of pain associated with TMJ disorders
      specific to arthralgic DJD.

PMID- 7586000
TI  - The effect of occlusal splint therapy on different curve parameters of
      axiographic TMJ tracings.
AB  - Computerized axiography was used as an objective instrumental method of
      evaluating the response of patients with temporomandibular joint (TMJ)
      symptomatology to occlusal splint therapy. Diagnosis was performed in a
      standardized manner by systematically analyzing TMJ path tracings obtained by
      computerized axiography. Thirty-six patients were axiographed before and after
      therapy with full-arch occlusal stabilizing appliances, followed by assessing the
      effect of therapy on various path curve parameters. The data obtained for the
      patient group treated with splints was compared to that of six patients also
      axiographed, but left untreated for a period of six weeks before a second TMJ
      tracing was obtained. The results show that splints have a certain effect on
      reciprocal TMJ clicking (response rate 67%). Retral stability and path
      characteristics are also substantially improved (response rates 44% and 40%).
      Less influence was noted on hypomobile joint paths (response rate 29%), the
      quality of movements (response rate 28%) and Bennett angle values (response rate
      23%). Patients with disk displacements without reduction were not treated with
      splints, they underwent surgery. Their results will be reported later. By
      contrast, TMJ tracings in the control group remained essentially unchanged.

PMID- 7585999
TI  - Mandibular exercises to control bruxism and deviation problems.
AB  - A discussion of bruxism, mandibular deviation and hypermobility problems
      producing temporomandibular joint (TMJ) and masticatory muscle pathology is
      presented. The pathophysiology of painful masticatory muscle hyperactivity, TMJ
      dysfunction and chondromalacia are presented. The role that pain mediators play
      in the degradation of TMJ fibrocartilage, acute synovitis and joint and muscle
      pain is analyzed. Isokinetic and stretching exercises are described to assist in
      correcting or preventing pathology and dysfunction of these structures.

PMID- 7586001
TI  - The TMJ-ear connection.
AB  - This article documents the existence of three structures that traverse through
      the petrotympanic fissure. These structures are the mandibular malleolar
      ligament, the chorda tympani nerve and the anterior tympanic artery. The
      mandibular malleolar ligament or the disk-malleolar ligament originates on the
      anterior process of the mallous. It traverses through the petro-tympanic fissure
      and attaches to the posterior portion of the capsule and disk of the
      temporomandibular joint. The chorda tympani nerve supplies sensory feeling to the
      posterior two thirds of the tongue. The anterior tympanic artery supplies blood
      to the area of the tympanic membrane. Clinical experience with implants that
      impinge or cover ear problems and other symptoms. Removal of these implants and
      placements with devices that do not cover these structures often relieve these
      symptoms.

PMID- 7586005
TI  - Headache.

PMID- 7586006
TI  - Problems and solutions. TMD patients who are gaggers.

PMID- 7586002
TI  - Evaluation of TMJ surgery in cases not responding to conservative treatment.
AB  - The aim of the study was to evaluate the treatment outcome after
      temporomandibular joint (TMJ) surgery, which was performed in 33 patients (27
      women and six men) between 1970 and 1986. Before surgery, the patients received
      different types of conservative treatment for an average time of 29 months. The
      most common diagnosis was anterior disk displacement (ADD) with or without
      reduction (n = 10), followed by unspecified arthralgia (n = 8), osteoarthrosis (n
      = 7) and ankylosis (n = 4). Standardized clinical records served as the basis for
      comparison of symptomatology at comparable time points. Furthermore, 31 of the 33
      patients were subjected to a clinical follow-up, including anamnestic, clinical,
      radiological and cast analysis, 2-17 years after operation. Pain, sleeping
      problems and consumption of analgesics were significantly reduced after surgery.
      The anamnestic, as well as the clinical dysfunction indices, according to
      Helkimo, were also significantly reduced. TMJ clicking was reduced, but
      crepitations increased in number. The best improvements were seen in patients
      with ADD without reduction and in patients with ankylosis.

PMID- 7586004
TI  - The MRI study as a diagnostic and therapeutic indicator in the non-surgical
      management of temporomandibular joint disorders: phase I management--a case
      report.
AB  - The dental profession frequently points to occlusion, muscle disorders or
      psychological stress as principal causes of temporomandibular joint (TMJ)
      disorders. Diagnosis and management is confusing, and no general consensus
      exists. Recent advances in magnetic resonance imaging (MRI) have allowed a means
      of evaluating large numbers of patients for internal derangements in an objective
      non-invasive fashion. This has unequivocally confirmed prior arthrographic and
      surgical observation that partial or complete dislocation of the articular disk
      with condylar compression of sensitive superior posterior joint space
      neurovascular elements is the principal pathophysiologic mechanism of TMJ
      disorders. TMJ disorders have been shown to be a general progression of
      degenerative joint disease characterized by joint space compression with
      displacement and degeneration of articular hard and soft tissues, most commonly
      the result of trauma. This article illustrates how the author has combined
      several different dental and medical diagnostic procedures with clinical
      therapeutic measures to manage patients to improved function and remission of
      symptoms by controlling the position of the joint hard structures in an objective
      fashion.

PMID- 7586003
TI  - Changes in the innervation of rabbit craniomandibular joint tissues associated
      with experimental induction of anterior disk displacement: histochemical and
      immunohistochemical studies.
AB  - We have previously reported that surgical induction of anterior disk displacement
      (ADD) in a rabbit craniomandibular joint (CMJ) leads to histopathological changes
      consistent with osteoarthritis. This paper reports the changes that were noted in
      the innervation of rabbit CMJ tissues following surgical induction of ADD. The
      right joint of 30 rabbits was exposed surgically and the discal attachments were
      severed except for the posterior discal attachment (bilaminar zone). The disk was
      then displaced anteriorly and sutured to the zygomatic arch. The left joints was
      used as sham-operated control. CMJ tissues were then removed after fixation and
      processed for histochemical localization of nerve fibers using the silver
      impregnation technique and immunohistochemical localization of neurofilaments
      using monoclonal antibodies. The results showed an absence of nerve fibers in the
      control and experimental disks and their presence in the control and experimental
      bilaminar zones. The bilaminar zone adhesions to the experimental condyles were
      also innervated. The spread of nerve fibers into the pathological fibrous
      adhesions surrounding the arthritic condyles in this animal model of ADD may
      indicate a possible mechanism of nociception in this disease.

PMID- 7586008
TI  - Introduction of macromolecules into living Dictyostelium cells by
      electroporation.
AB  - An attempt was made to optimize conditions for introduction of macromolecules
      into Dictyostelium cells by electroporation. The amount of fluorescein-labeled
      bovine serum albumin (FITC-BSA) introduced into cells was measured by fluorometry
      after extraction of FITC-BSA from cells with detergent. The amount increased as
      the applied voltage and capacitance of the discharger were increased. However,
      the survival of cells decreased at higher voltages and elevated capacitance. FITC
      BSA was introduced into 80-90% of treated cells. FITC-BSA at 0.25 mg/ml was
      introduced into cells under optimum conditions when the concentration of the
      extracellular protein was 2.5 mg/ml. Several discharges in sequence improved the
      extent of introduction of FITC-BSA although viability decreased. There was a
      linear correlation between final intracellular concentration and the initial
      extracellular concentration of FITC-BSA, suggesting the possible quantitative
      introduction of the protein into cells. The membrane pores that opened during
      electroporation closed within 2.5 sec after the discharge. FITC-labeled dextran
      with molecular weights of less than 5 x 10(5) were able to pass through these
      pores. Our results show that electroporation provides a quantitative and
      reproducible method for introduction of macromolecules into living Dictyostelium
      cells.

PMID- 7586007
TI  - Chewing pattern analysis in TMD patients with and without internal derangement:
      Part I.
AB  - In order to investigate the chewing movement of temporomandibular disorders (TMD)
      patients with and without internal derangement of the temporomandibular joint
      (TMJ), analysis of the envelope of motion during chewing was performed in 103 TMD
      patients with unilateral internal derangement (ID group), 94 TMD patients without
      internal derangement (NID group) and 10 normal subjects (normal group). The
      analysis of numeric parameters revealed that the ID group demonstrated a
      significantly restricted range of motion compared to the NID or normal groups,
      and the NID group demonstrated significant irregularity of chewing compared to
      the ID or normal groups. The analysis of chewing also demonstrated that the
      chewing pattern for the ID group demonstrated more frequent deviation of the
      turning point to the nonchewing side in the frontal plane and a narrow
      anteroposterior pattern in the sagittal plane compared to the other groups. No
      characteristic chewing patterns were identified for the NID group.

PMID- 7586009
TI  - Functional analysis and DNA polymorphism of the tandemly repeated sequences in
      the 5'-terminal regulatory region of the human gene for thymidylate synthase.
AB  - Triple tandemly repeated sequences and the corresponding complementary sequence
      are known to exist in the 5'-terminal regulatory region of the human gene for
      thymidylate synthase (TS). To examine the function of these sequences, a set of
      deletion mutants was prepared and used in a transient expression assay. The
      results showed that at least one repeated sequence and its complementary sequence
      were necessary for the efficient expression of the gene. As another approach to
      understanding the function of this unique structure, DNA polymorphism in the same
      region was analyzed. In addition to the TS gene with the triple tandem repeat,
      the TS gene with a double tandem repeat was found in genomes of normal human
      subjects at an estimated frequency of 19% when genomes of 21 unrelated Japanese
      were analyzed. The expression activity of a reporter gene linked to the promoter
      region of the human TS genes with the two types of repeated sequence was examined
      and the result showed that the expression activity of the gene with the double
      repeat was lower than that of the gene with the triple repeat in the transient
      expression assay. Thus, it appears that the unique repeated sequences in the 5'
      terminal region of the human TS gene are polymorphic and contribute to the
      efficiency of expression of the gene.

PMID- 7586010
TI  - Chondroitin sulfate immobilized onto culture substrates modulates DNA synthesis,
      tyrosine aminotransferase induction, and intercellular communication in primary
      rat hepatocytes.
AB  - Newly prepared phosphatidylethanolamine (PE) conjugates of glycosaminoglycans
      (GAGs) enabled us to immobilize GAGs to solid phase through hydrophobic
      interaction. Using these compounds, called GAG-PEs, we studied the effects of
      GAGs immobilized to culture plates coated with various extracellular matrix (ECM)
      proteins in terms of cell-substrate adhesion, DNA synthesis, tyrosine
      aminotransferase (TAT) induction, and intercellular communication in primary rat
      hepatocytes. Treatment with chondroitin sulfate (CS)-PE at 10 micrograms/ml made
      laminin, fibronectin, vitronectin, and collagens type I-V less adhesive as
      substrates for cell attachment and inhibited cell spreading on these substrates.
      The effect on cell attachment was lost after long incubations over 2 h. Dermatan
      sulfate (DS)-PE was also inhibitory, but less effective. The conjugates of
      heparan sulfate (HS), heparin, and hyaluronan were much less effective. DNA
      synthesis initiated by EGF in the culture on laminin substrates was inhibited
      most strongly by CS-PE, as well as by DS-PE and hyaluronan-PE, but not by either
      HS-PE or heparin-PE. With type I collagen substrates, GAG-PEs had similar effects
      but to lesser extent. TAT induction in the culture on laminin substrates but not
      on type I collagen substrates was significantly enhanced by CS-PE. In terms of
      DNA synthesis and TAT induction, the culture on laminin substrates treated with
      CS-PE was comparable to that at higher cell density on the non-treated laminin
      substrates. Intercellular communication assessed by dye coupling was maintained
      longer on the substrates treated with CS-PE. Taken together, our results
      demonstrate that CS immobilized especially onto laminin substrates inhibits the
      growth of hepatocytes and enhances their differentiated functions by modulating
      cell-ECM protein interactions.

PMID- 7586011
TI  - Enhancement of adhesive property of epithelial cell line Mm2T by culture in the
      presence of methylated vitamin B12.
AB  - A thymic epithelial cell line Mm2T was cultured in a medium containing a high
      concentration (100 micrograms/ml) of methylated vitamin B12 (CH3-B12). After 19
      days, cells were found to have a flat phenotype, to have lost the floating cells
      which were observed in the control cells at the confluent stage, and to have
      acquired a resistance to trypsin. However, treatment of the CH3-B12-treated cells
      with EDTA resulted in a dissociation of cell-to-cell contact and reaggregation
      was achieved by addition of Ca2+, indicating the involvement of Ca2+ ion in cell
      to-cell contact. Electron microscopic analyses revealed that the CH3-B12-treated
      cells were nearly square in their vertical section, which was in contrast to the
      dome-shaped feature of the control cells, and their cell-to-cell contact area was
      significantly widespread, as compared to those of the control, indicating that
      Mm2T cells acquires an adhesive property by treatment with CH3-B12. Biochemical
      analyses of both cells indicated that the concentration of glucosylceramide in
      the CH3-B12-treated cells was higher than that of the control. Free glucose
      characteristically inhibited the reattachment of cells dissociated with EDTA,
      suggesting the involvement of glucose in the cell-to-cell adhesion of CH3-B12
      treated cells. In addition, WGA-binding glycoconjugates were intensely observed
      in the boundary region of CH3-B12-treated cells by immunohistochemical staining,
      but not in that of the control cells. It is suggested that CH3-B12 may affect the
      morphological alteration of Mm2T by enhancing cell adhesion through elevated
      expression of the C-type lectin.

PMID- 7586012
TI  - Serum factor(s) stimulating cumulus expansion in porcine oocyte-cumulus complexes
      matured and fertilized in vitro.
AB  - We have investigated the factor(s) present in serum that stimulate cumulus
      expansion (accumulation of hyaluronic acid in the intercellular space of cumulus
      cells) and male pronucleus (mPN) formation in porcine oocytes matured and
      fertilized in vitro. After 24 hr of culture, oocyte-cumulus complexes that
      matured in the serum of pig, cow, rabbit and rat showed an expansion of the
      surrounding cumulus cell matrices. The cumulus expansion stimulating effect is
      not species-specific. Porcine serum was fractionated by ultracentrifugation at
      220,000 x g at 10 degrees C for 48 hr, resulting in four fractions. The oocyte
      cumulus complexes that matured in the 2nd fraction exhibited a marked expansion
      of the cumulus cell layers, including the corona radiata. Complexes cultured in
      the remaining fractions, however, showed very little or no expansion. There was
      no expansion of the oocytectomized complexes matured in the 2nd fraction. Serum
      was not effective in the formation of the male pronucleus. The active factor(s)
      was heat stable at 100 degrees C for 30 min and showed a relatively strong
      activity at a molecular weight of > 1.0 and < 6.5 kDa. These results indicate
      that serum contains a low molecular weight, heat stable factor(s) that acts on
      the oocyte to stimulate cumulus expansion.

PMID- 7586014
TI  - The vegetative micronucleus has a critical role in maintenance of cortical
      structure in Tetrahymena thermophila.
AB  - The vegetative role of the germinal micronucleus of Tetrahymena thermophila was
      studied. Amicronucleate cells that had spontaneously arisen in star strains (very
      aged cones with defective micronuclei) were observed in B* as well as in A* and
      in C* and were found to lack the oral apparatus and to have disordered ciliary
      rows. To reduce uncertainty given the very small micronucleus and possible
      effects of aging factors, we induced amicronucleate cells in a young clone by
      treatment with the antitubulin drug, nocodazole, and observed their cortical
      structure and nuclei. Amicronucleate cells gradually lost their oral apparatus
      and then their ciliary rows became disordered, even without cell division, and
      they became crinkled cells. It can be concluded that the vegetative micronucleus
      appears to play a critical role in the maintenance of the cortical structure,
      especially of the oral apparatus.

PMID- 7586013
TI  - Effects of SH-blocking compounds on the energy metabolism in isolated rat
      hepatocytes.
AB  - To investigate the importance of SH-groups in the energy metabolism of liver
      cells, isolated rat hepatocytes were exposed to various SH-blocking compounds.
      After 1.0 hr exposure, the cells were analyzed for the content of glycogen,
      lactate, pyruvate, ATP and the rate of oxygen consumption. Without affecting the
      cell viability, PCMB, PCMBS, mersalyl, NEM, DTP and DSF were found to decrease
      glycogen levels, whereas the disulphide reagent CDPS did not affect this
      endogenous energy reserve. Lactate and pyruvate levels were decreased by the
      organic mercury compounds, whereas NEM, DTP and DSF stimulated the formation of
      lactate, without affecting the levels of pyruvate. In both situations the oxygen
      consumption was slightly decreased. The FCCP uncoupled oxygen consumption was not
      affected. Up to the point of loss of cell viability, as measured by trypan blue
      exclusion and LDH-leakage, the liver cells maintained their ATP levels, during
      exposure to the various SH-reagents. In conclusion, the results with organic
      mercury compounds suggest a reaction of these agents with SH-groups in the outer
      membrane of cells, having an inhibiting effect on the glucose uptake. The most
      prominent effect of DTP, DSF and NEM was an increased lactate formation, implying
      an intracellular effect, most probably in the TCA-cycle.

PMID- 7586015
TI  - [Dopaminergic receptors--nomenclature and classification of types and subtypes].
AB  - At present, dopamine receptors are divided into two groups, dopamine D1-like
      receptors and dopamine D2-like receptors. In the study of these receptors,
      application of molecular biology methods has led to the identification of several
      structurally distinct subfamilies of receptors. D1-like subfamily contains D2,
      D3, and D4 receptors. These receptors are the primary targets in treatment of
      schizophrenia, Parkinson's disease and Huntington's chorea. Some of the
      neuroleptics have very selective action on certain subtypes of dopamine
      receptors, however, it seems that the efficient treatment of e.g. schizophrenia
      can be reached only by drugs which affect not only dopaminergic receptors but
      also 5-HT and possibly other receptors. It is of interest that the antipsychotic
      drugs originally led to the discovery of dopamine receptors and their subtypes
      and now, in turn, these receptors are used to search for more selective drugs
      with antipsychotic and antiparkinsonic effects.

PMID- 7586016
TI  - [5-hydroxytryptamine (serotonin) receptors--nomenclature and classification of
      types and subtypes].
AB  - 5-HT receptors represent a superfamily of receptors with the largest known number
      of receptor subtypes. At present 15 receptor subtypes of three groups has been
      recognized. The 5-HT1 subfamily of receptors contains subtypes 5-HT1A, 5-HT1B, 5
      HT1D, 5-HT1E, and 5-HT1F; activation of all of them results in the inhibition of
      adenylylcyclase. The subfamily of 5-HT2 contains subtypes 5-HT2A, 5-HT2B, and 5
      HT2C; their activation leads to the stimulation of PLC. Finally, subfamily of
      miscellaneous 5-HT receptors contains subtypes 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5
      HT7; some of them has been cloned, however, our knowledge on their function is
      still minimal. 5-HT receptors participate in many physiological functions and a
      disturbance in serotonergic neurotransmission might cause several types of
      disease. 5-HT plays an important role in depression; to cure this disease, drugs
      which increase levels of this neurotransmitter are used. A new drug group called
      Selective Serotonin Reuptake Inhibitors (SSRI) has been recently discovered.
      These drugs block the reuptake of 5-HT into nerve endings. There is an intensive
      search for new selective agonists as well as antagonists which could be use not
      only in the classification of receptor subtypes but which also possess certain
      therapeutic potential.

PMID- 7586017
TI  - [Purinergic receptors--nomenclature and classification of types and subtypes].
AB  - The purpose of this review is to present current knowledge regarding purinergic
      receptors and their subtypes. The main endogenous ligans for these receptors are
      adenosine and ATP which are released from cells and neurons under various
      pathophysiological conditions, and adenine nucleotides which are released as
      contransmiters together with noradrenaline, acetylcholine and substance P.
      Purinergic receptors which are present in various tissues and mediate numerous
      physiological effects can be divided into two main groups, P1 (for adenosine) and
      P2 (for adenine nucleotides) receptors. Both these types are further divided into
      subtypes. P1 receptors are better characterized than P2 receptors whose
      classification must be regarded as tentative rather than definitive. P1 receptors
      are named according to their natural ligand adenosine as A1, A2a, A2b, A3 and
      possibly A4 receptors. Their characteristics are summarized in tables which also
      present the main selective agonists and antagonists of their receptors. Since the
      classification of P2 receptors is still tenative, their nomenclatue does not
      follow the exact rules which are provided by IUPHAR. P2 receptors are subdivided
      into these subtypes: P2X, P2Y, P2U, P2T, P2Z and P2D. The article also lists the
      main agonists and antagonists for these receptors. The introduction of new
      selective agonists and antagonists not only helps to classify various receptors
      subtypes of purinoceptors but it also has a big therapeutic potential for various
      diseases.

PMID- 7586018
TI  - The muscle biopsy: a procedural overview.

PMID- 7586019
TI  - [Endothelin--a cardiovascular regulatory peptide. I. Physiologic activity].
AB  - Review article informs about the physiological and pathophysiological effects of
      the most potent vasoconstrictor agent endothelin (ET). This vasoactive
      polypeptide (21-aminoacids) is of the endothelial origin, it has three isoforms
      (ET-1, ET-2, ET-3), and it significantly participates in regulation of the
      vascular tone. Exploration of effects of the "family" of endothelins has expanded
      very dynamically since their discovery in eighties of the present century. At
      present, these studies affect almost all fields of medicine. The first part of
      the article brings information on the structure, biosynthesis and production of
      endothelins under the physiological conditions. Profound attention is given both
      to their effects on the cellular level and on the level of individual systems of
      the human organism. In conclusions the significance of endothelin receptor
      antagonists for the comprehensive explanation of endothelins role in the
      cardiovascular regulation and in the pathophysiology of those types of disorders
      and diseases which are linked to their activation is emphasized.

PMID- 7586021
TI  - [Should there be something new in the teaching of physiology in medical
      schools?].

PMID- 7586020
TI  - [Endothelin--a cardiovascular regulatory peptide. II. Outline of its
      pathophysiologic activity].
AB  - Review article informs about the physiological and pathophysiological effects of
      the most potent vasoconstrictor agent endothelin (ET). This vasoactive
      polypeptide (21-aminoacid) has three izoforms (ET-1, ET-2, ET-3) and participates
      on regulation of the vascular tone and on remodelling of the vascular and
      myocardial wall. Article is focused on the effects of endothelins on the
      cardiovascular system, kidney and the central nervous system with respect to
      their expected role in the initiation and sustaining of disorders and diseases
      accompanied by the local and general vasconstriction. Findings concerning the
      role of endothelins in the pathogenesis of arterial hypertension, myocardial
      infarction, congestive heart failure, atherosclerosis, shock conditions, renal
      failure, and vasospasm following the subarachnoidhem orrage are discussed.

PMID- 7586023
TI  - [Ioannes Marcus Marci (1595-1667)].

PMID- 7586022
TI  - [J.E. Purkinje--an educator].

PMID- 7586025
TI  - Expression of the FOX1 gene of Saccharomyces cerevisiae is regulated by carbon
      source, but not by the known glucose repression genes.
AB  - We have investigated the regulation of expression of the FOX1 gene of
      Saccharomyces cerevisiae which encodes acyl-CoA oxidase, the first enzyme in the
      peroxisomal beta oxidation of fatty acids. We have found that the FOX1 steady
      state mRNA level is repressed by glucose, partially induced by ethanol (but not
      by raffinose) and fully induced by oleic acid as a carbon source. Glucose
      repression was observed even if cultures were grown to stationary phase; however,
      if the glucose supply was limited initially then partial induction of FOX1 mRNA
      occurred upon growth to high cell density. A variety of mutants are known to
      affect the glucose repression of many genes, including the FOX3 gene which
      encodes the thiolase activity in peroxisomal beta oxidation. However, upon
      examination none of these mutants showed de-repression of FOX1 expression.
      Similarly we investigated the role of two inducers of genes encoding peroxisomal
      enzymes (namely SNF1 and ADR1). No evidence was found to suggest that either of
      these plays a significant role in the induction of FOX1 mRNA levels. These
      observations indicate that the regulation of FOX1 is under the control of as yet
      unidentified genes involved in catabolite repression and suggest that the
      regulatory circuit influencing acyl CoA oxidase activity, and hence beta
      oxidation and peroxisome function, is significantly different than that which
      might have been assumed from other studies.

PMID- 7586026
TI  - NCA3, a nuclear gene involved in the mitochondrial expression of subunits 6 and 8
      of the Fo-F1 ATP synthase of S. cerevisiae.
AB  - Respiratory-competent nuclear mutants have been isolated which presented a
      cryosensitive phenotype on a non-fermentative carbon source, due to a
      dysfunctioning of the mitochondrial F1-Fo ATP synthase which results from a
      relative defect in subunits 6 and 8 of the Fo sector. Both proteins are mtDNA
      encoded, but the defect is due to the simultaneous presence of a mutation in two
      unlinked nuclear genes (NCA2 and NCA3, for Nuclear Control of ATPase) promoting a
      modification of the expression of the ATP8-ATP6 co-transcript (formerly denoted
      AAP1-OLI2). This co-transcript matures at a unique site to give two cotranscripts
      of 5.2 and 4.6 kb in length: in the mutant, the 5.2-kb co-transcript was greatly
      lowered. NCA3 was isolated from a wild-type yeast genomic library by genetic
      complementation. The level of the 5.2-kb transcript, like the synthesis of
      subunits 6 and 8, was partly restored in the transformed strain. A 1011
      nucleotide ORF was identified that encodes an hydrophilic protein of 35417 Da.
      Disruption of chromosomal DNA within the reading frame promoted a dramatic
      decrease of the 5.2-kb mRNA but did not abolish the respiratory competence of a
      wild-type strain. NCA3 is located on chromosome IV and produces a single 1780-b
      transcript.

PMID- 7586024
TI  - Genetic and biochemical dissection of the mitochondrial protein-import machinery.
AB  - Mitochondria import most of their proteins from the cytosol. A multi-subunit
      machinery accomplishes the translocation of precursor polypeptides into and
      across the two mitochondrial membranes. Within recent years more than 20
      different proteins have been identified which are involved in mitochondrial
      protein import. This review summarizes the successful genetic and biochemical
      approaches that led to the identification of these transport and folding
      components. The identification and functional characterization of the components
      can be seen as a paradigm for the molecular analysis of a complex biological
      process by a combination of biochemical and genetic procedures.

PMID- 7586028
TI  - Mutants of Saccharomyces cerevisiae sensitive to oxidative and osmotic stress.
AB  - Although oxidative stress is involved in many human diseases, little is known of
      its molecular basis in eukaryotes. In a genetic approach, S. cerevisiae was used
      to identify elements involved in oxidative stress. By using hydrogen peroxide as
      an agent for oxidative stress, 34 mutants were identified. All mutants were
      recessive and fell into 16 complementation groups (pos1 to pos16 for peroxide
      sensitivity). They corresponded to single mutations as shown by a 2:2 segregation
      pattern. Enzymes reportedly involved in oxidative stress, such as glucose-6
      phosphate dehydrogenase, glutathione reductase, superoxide dismutase, as well as
      glutathione concentrations, were investigated in wild-type and mutant-cells. One
      complementation group lacked glucose-6-phosphate dehydrogenase and was shown to
      be allelic to the glucose-6-phosphate dehydrogenase structural gene ZWF1/MET19.
      In other mutants all enzymes supposedly involved in oxidative-stress resistance
      were still present. However, several mutants showed strongly elevated levels of
      glutathione reductase, gluconate-6-phosphate dehydrogenase and glucose-6
      phosphate dehydrogenase. One complementation group, pos9, was highly sensitive to
      oxidative stress and revealed the same growth phenotype as the previously
      described yap1/par1 mutant coding for the yeast homologue of mammalian
      transcriptional activator protein, c-Jun, of the proto-oncogenic AP-1 complex.
      However, unlike par1 mutants, which showed diminished activities of oxidative
      stress enzymes and glutathion level, the pos9 mutants did not reveal any such
      changes. In contrast to other recombinants between pos mutations and par1, the
      sensitivity did not further increase in par1 pos9 recombinants, which may
      indicate that both mutations belong to the same regulating circuit.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7586027
TI  - A mutant allele of the SUP45 (SAL4) gene of Saccharomyces cerevisiae shows
      temperature-dependent allosuppressor and omnipotent suppressor phenotypes.
AB  - Using a plasmid-based termination-read-through assay, the sal4-2 conditional
      lethal (temperature-sensitive) allele of the SUP45 (SAL4) gene was shown to
      enhance the efficiency of the weak ochre suppressor tRNA SUQ5 some 10-fold at 30
      degrees C. Additionally, this allele increased the suppressor efficiency of SRM2
      2, a weak tRNA(Gln) ochre suppressor, indicating that the allosuppressor
      phenotype is not SUQ5-specific. A sup+ sal4-2 strain also showed a temperature
      dependent omnipotent suppressor phenotype, enhancing readthrough of all three
      termination codons. Combining the sal4-2 allele with an efficient tRNA nonsense
      suppressor (SUP4) increased the temperature-sensitivity of that strain,
      indicating that enhanced nonsense suppressor levels contribute to the conditional
      lethality conferred by the sal4-2 allele. However, UGA suppression levels in a
      sup+ sal4-2 strain following a shift to the non-permissive temperature reached a
      maximum significantly below that exhibited by a non-temperature sensitive SUP4
      suppressor strain. Enhanced nonsense suppression may not therefore be the primary
      cause of the conditional-lethality of this allele. These data indicate a role for
      Sup45p in translation termination, and possibly in an additional, as yet
      unidentified, cellular process.

PMID- 7586029
TI  - Cloning and sequencing of cellulase cDNA from Aspergillus kawachii and its
      expression in Saccharomyces cerevisiae.
AB  - The cDNA encoding the endo-beta-1,4-glucanase (carboxymethylcellulase; CMCase-I)
      from Aspergillus kawachii IFO 4308 was cloned. Nucleotide-sequence analysis of
      the cloned cDNA insert showed a 717-bp open reading frame that encoded a protein
      of 239 amino-acid residues. The predicted amino-acid sequence of the mature
      protein had considerable homology with the protein sequence of the FI-CMCase of
      Aspergillus aculeatus. The cDNA was introduced into Saccharomyces cerevisiae. The
      expressed enzyme had carboxylmethylcellulase activity, identified by clear zones
      on a CMC-agar plate after Congo Red staining.

PMID- 7586031
TI  - Electrophoretic karyotype of the astaxanthin-producing yeast Phaffia rhodozyma.
AB  - The electrophoretic karyotype of three different strains of Phaffia rhodozyma was
      determined by contour-clamped homogeneous electric field (CHEF)-gel
      electrophoresis. Significant differences in electrophoretic karyotyping patterns
      were found among the three strains studied. Between nine and 17 bands were
      observed. The size of these bands, based on their migration relative to the
      chromosomal DNA of Schizosaccharomyces pombe, Hansenula wingei was estimated to
      be between 0.48 and 3.1 Mb.

PMID- 7586032
TI  - Heterozygosity at the b mating-type locus attenuates fusion in Ustilago maydis.
AB  - Mating and pathogenesis of the corn smut fungus, Ustilago maydis, are controlled
      by two unlinked mating-type loci, a and b. Yeast-like haploids that differ at
      both loci are compatible and fuse to establish a pathogenic dikaryon. Mating is
      assayed in vitro by co-inoculation on culture medium containing activated
      charcoal; compatible combinations have a characteristic "fuzzy" appearance caused
      by the growth of aerial hyphae. In general, this test has not been useful for
      assaying the mating ability of strains that are already mycelial (e.g., those
      heterozygous at b or at both mating-type loci). Using an assay for cytoduction
      involving transfer of a mitochondrial marker during transient cell fusion, and
      engineered strains with defined genotypes, we examined the mating abilities of
      strains heterozygous or hemizygous at the mating-type loci. The data (which have
      not been available from conventional pathogenicity or plate mating tests) show
      that heterozygosity at b attenuates fusion in haploid and diploid strains,
      whereas strains heterozygous at a retain the ability to fuse with a compatible
      haploid partner. It appears, therefore, that subsequent fusion events are
      attenuated once fusion has occurred to establish the U. maydis dikaryon.

PMID- 7586033
TI  - Presence of a P1 bacteriophage sequence in transforming plasmids of Pleurotus
      ostreatus.
AB  - Replicative plasmids pP01 and pP02, recovered from Pleurotus ostreatus
      transformants, contain an insert of bacteriophage origin. These plasmids have
      been amplified by the polymerase chain reaction (PCR) and have been shown to
      represent a low-grade component in the initial preparation of the vector pAN7-1.
      The pP01 and pP02 plasmids share an insert (P01A) of virtual identity with a SmaI
      BamHI genomic fragment of P 1 bacteriophage and retain remnants of a polylinker
      at the 5' end of this fragment. Such an insert undoubtedly represents an in vitro
      generated event and did not arise, as suggested previously, by recombination of
      pAN7-1 with the P. ostreatus genome. The P. ostreatus transformants, however, do
      select for the minority pP0 plasmid, apparently recognizing the P01A insert as a
      heterologous or surrogate replicon.

PMID- 7586030
TI  - Molecular cloning of the meiosis-induced rec10 gene of Schizosaccharomyces pombe.
AB  - The meiotic recombination gene rec10, which encodes a region-specific activator
      of recombination in Schizosaccharomyces pombe, has been cloned by genetic
      complementation and its nucleotide sequence determined. The rec10 gene was
      identified in a 5.6-kb cloned fragment by partial-deletion and insertion
      experiments. The nucleotide sequence of 3.5 kb of this clone revealed an open
      reading frame (ORF) encoding a 791 amino-acid polypeptide for the rec10 gene
      product. During meiosis, thermally induced in a temperature-sensitive pat1-114
      mutant, the transcript of rec10 was induced to a maximal level at 2-3 h but was
      present at much lower levels before and after this time. The transient induction
      of the rec10 transcript and the rec10 mutant phenotype suggest that the rec10
      gene product is involved primarily in the early steps of meiotic recombination
      localized to chromosome III in S. pombe.

PMID- 7586034
TI  - Sequence diversity and unusual variability at the het-c locus involved in
      vegetative incompatibility in the fungus Podospora anserina.
AB  - The het-c locus of the filamentous fungus Podospora anserina controls
      heterokaryon formation through genetic interaction with alleles of the unlinked
      loci het-e and het-d. We have isolated four wild-type and two mutant alleles of
      the het-c locus. A comparison of the predicted proteins encoded by the different
      wild-type alleles revealed an unusual high level of amino-acid replacements
      compared to silent polymorphisms but only one amino-acid difference is sufficient
      to modify the specificity of het-c alleles. Chimeric genes constructed in vitro
      may exhibit a new specificity different from that of any known wild-type allele.

PMID- 7586036
TI  - The replication origin position and its relationship to a negative trans-acting
      transcription regulator encoded by Dictyostelium discoideum nuclear plasmid Ddp1.
AB  - The replication origin of the Dictyostelium discoideum plasmid Ddp1 was localized
      to a 543-bp region. This includes most of the AT-rich intergenic region between
      the G1 and G5/D6 genes containing both of their promoters and multiple copies of
      a TTTTGACT repeat. The G5/D6 gene, which lies adjacent to, and partially
      overlaps, the 543-bp origin region, encodes a trans-acting factor that negatively
      regulates transcription of the G4/D5 gene. Inactivation of the G5/D6 gene led to
      expression of a transcript (G6) 0.2 kb larger than the D5 transcript from the
      G4/D5 gene in vegetative and developing cells. The G5/D6 gene also regulates
      transcription of the G1, G2/G3/D4 and G5/D6 genes either alone or in concert with
      other Ddp1 gene products.

PMID- 7586035
TI  - Cloning of the Rhizopus niveus pyr4 gene and its use for the transformation of
      Rhizopus delemar.
AB  - We have cloned a pyr4 gene encoding orotidine-5'-monophosphate decarboxylase of
      the filamentous fungus Rhizopus niveus. The pyr4 gene of R. nivens has an open
      reading frame composed of 265 amino-acid residues and has two putative introns.
      We have also isolated a pyr4 mutant of Rhizopus delemar from 5-fluoroorotic acid
      resistant mutants and transformed it with the pyr4 gene of R. niveus as a
      selectable marker. Introduced DNA was integrated into the chromosome in a
      multiple tandem array. The mitotic stability of the introduced DNA was increased
      by a repeated sporulation process. The expression of the Escherichia coli beta
      glucuronidase gene in R. delemar was successfully obtained under the control of
      the pgk2 gene promoter of R. niveus by co-transformation with the pyr4 gene.

PMID- 7586039
TI  - [Long-term results of scleroplasty surgery in children].
AB  - The authors presents results of scleroplastic operations in 411 children (773
      eyes) followed up to 7 years after surgery: Most frequently eyes with the
      diagnosis myopia progressiva (397 = 51.4%) and myopia gravis (330 = 12.7%) were
      operated. The mean age at the time of operation was 12.2 +/- 3.0 years myopia
      progressiva and 10.8 +/- 3.9 years in myopia gravis. The difference was
      statistically significant (p = 0.0002). The visual acuity was on average better
      throughout the follow-up period in both main diagnoses, as compared with initial
      values. The progression of myopia (subjective refraction) slowed down markedly
      after surgery and was 0.26 D/year in myopia progressiva and 0.23 D/year in myopia
      gravis. The authors recommend scleroplasty to prevent significant progression of
      myopia and for longterm preservation of visual functions.

PMID- 7586037
TI  - Selective amplification of a mammoth mitochondrial cytochrome b fragment using an
      elephant-specific primer.

PMID- 7586038
TI  - Remnants of a DNA polymerase gene in the mitochondrial DNA of Marchantia
      polymorpha.

PMID- 7586040
TI  - [Use of the DK-Line OPSIA liquid perfluorocarbon].
AB  - Since May 1993 to February 1995 we have used "DK-LINE" OPSIA in 137 patients in
      whom were 161 procedures on 141 eyes performed. It was used in 116 retinal
      detachments, 29 of them were posttraumatic. 28x in the eyes with proliferative
      diabetic retinopathy, 8x by injuries of the posterior segment of the eye, 5x in
      dislocated lenses and 3x by the removal of subretinal membranes. At the end of
      retinal detachment surgery was retina attached in 94.2%. Peroperatively we
      recorded subretinal migration of PFCL in 16 cases. 13x was removed peroperatively
      and 3x later by the reoperations. In three aphakic eyes we recorded
      postoperatively small bubble of PFCL at the bottom of the anterior chamber. From
      two of them was fully removed by paracenthesis and from the third by the
      reoperation. Only 1x we used an internal tamponade in duration of 5 day. We
      recorded serious sero-fibrinous exudation in the anterior chamber and in the
      vitreous cavity over the level of PFCL.

PMID- 7586042
TI  - [Neodymium:YAG trabeculotomy].
AB  - The author presents the results of ND: YAG trabeculotomy on 10 eyes with open
      angle glaucoma. The surgery has been carried out as last treatment before
      trabeculectomy. The mean intraocular pressure (IOP) before laser surgery was 35
      +/- 5.2 mm Hg. The IOP decrease below 22.0 mm Hg has been achieved in 50% of
      eyes. The mean follow-up of the patients was 1 year. Complications included
      transient postoperative IOP elevation (six eyes) and angle bleeding (three eyes).

PMID- 7586041
TI  - [Therapy of the fibrin reaction after intraocular surgery using fibrinolytic
      agents].
AB  - The presence of fibrinous reaction after some intraocular surgery causes in some
      cases the reduction of visual acuity. In our study we aimed at fibrinous response
      after ECCE with posterior chamber IOL implantation and the possibility of affect
      and treatment of the fibrinous reaction. From January 1991 to December 1993, 1160
      ECCE with implantation IOL were performed at Department of Ophthalmology
      Postgraduate Institute in Bratislava, Slovakia. The fibrinous reaction was
      encounted in 110 eyes (9.48%). Some of fibrinolytics which are commonly applied
      on the treatment of internal medicine can be used safely for fibrinous reaction
      after intraocular surgery. We used Fraxiparine (Sanofi, Choay), which was applied
      subconjunctivally in dose of 500 U.I.Axa. The treatment of fibrinous reaction
      with corticosteroids and Fraxiparine was compared. The results proved that after
      treatment with Fraxiparine the fibrinous reaction disappeared sooner. We have not
      found out any complications after application of Fraxiparine.

PMID- 7586044
TI  - [Relation between myopia and intelligence].
AB  - The objective of the investigation to confirm the authors experience and data
      from the literature that refractory myopia is as a rule associated with a higher
      of intelligence. In the first part one of the authors evaluated a group of 14
      year-old myopic children with hypermetropia children of the same age. For
      evaluation she used the intelligence quotient (IQ) and assessment by teachers
      before the children left elementary school. The results are clearly in flavour of
      the myopia children. In the second part the authors evaluated the intelligence of
      15-18-year-old myopic secondary school pupils as compared with their classmates.
      Assuring that myopia is usually associated with higher intelligence and makes
      thus more profound education possible, they compared the students with
      apprentires trained to be cooks and waiters. The myopic students won again. Arong
      students there were 36.8% myopic, among appretices only 8%. The mean progress of
      students is 1.99, of apprentices only 2.68%. The myopic students have a general
      better progress and better marks in mathematics than their classmates without
      refractory defects (1.86:2.07 and 2.14:2.39). Based on the results of the
      investigation the authors assume that they were able to confirm data in the
      literature that myopic students are on average more intelligent that their poors
      of the same age.

PMID- 7586045
TI  - [Diabetic retinopathy].

PMID- 7586046
TI  - [Decompression of the optic nerve sheath].

PMID- 7586048
TI  - Induction of metallothionein synthesis by glutathione depletion after trans- and
      cis-stilbene oxide administration in rats.
AB  - To investigate the relationship between glutathione (GSH) depletion and
      metallothionein (MT) synthesis, the effects of substrates and an inhibitor of GSH
      S-transferases on concentrations of hepatic GSH, zinc (Zn) and MT were studied in
      rats. Trans-stilbene oxide (TSO) is an inducer of drug metabolizing enzymes and
      also a substrate of GSH S-transferase, whereby it covalently reacts with and
      depletes GSH. The hepatic GSH level was decreased to 25% of the control 2 h after
      injection of TSO, and returned to the control level by 24 h. TSO significantly
      increased hepatic concentrations of Zn and MT in a dose-dependent manner. Two
      isoforms of MT (MT-I and MT-II) were increased by TSO; MT-II was the dominant
      form. Pretreatment with buthionine sulfoximine (BSO), an inhibitor of GSH
      synthesis, enhanced MT synthesis itself as well as that induced by TSO and cis
      stilbene oxide (CSO). On the contrary, infection into rats of perfluorodecanoic
      acid (PFDA), an inhibitor of GSH S-transferase, resulted in a decrease in basal
      levels of Zn, and prevented the increase in MT synthesis by TSO and CSO. These
      results suggest that the decrease of GSH concentration in the liver which causes
      oxidative stress conditions may be related to MT induction.

PMID- 7586047
TI  - Determination of structure-activity relationships of Annonaceous acetogenins by
      inhibition of oxygen uptake in rat liver mitochondria.
AB  - A new group of natural compounds, the Annonaceous acetogenins, have recently been
      determined to inhibit ATP production at a similar site of action and higher
      levels of potency as rotenone, i.e., at NADH-ubiquinone oxido-reductase, complex
      I of the mitochondrial electron-transport chain. The acetogenins had earlier been
      determined to be pesticidal, antimalarial, antimicrobial, anti-parasitic,
      cytotoxic, and in vivo active as potentially new antitumor agents. In order to
      determine structural activity relationships (SARs) among these compounds, at the
      subcellular level, several available acetogenins have been tested. Data obtained,
      from the inhibition of oxygen consumption by rat liver mitochondria, demonstrated
      that all of the twenty acetogenins tested are active with IC50 values in the
      range of 15-800 nM/mg protein. The IC50 value of rotenone was 17 nM/mg protein.
      The bis-adjacent THF ring acetogenins and the bis-nonadjacent THF ring compounds
      are about ten times more active than the mono-THF ring acetogenins. Overall, 30
      OH and 31-OH-bullatacinone were the most active and were slightly more active
      than rotenone. The least active were the 4-deoxy bis-adjacent THF ring compounds
      followed by the mono-THF ring group. There was some variation between the groups,
      e.g., within the bis-adjacent and mono-THF ring groups, the alpha, beta
      unsaturated-gamma-lactones were less active than the keto-lactones, but this
      observation was reversed for one of the pairs of bis-nonadjacent THF ring
      acetogenins. Additional hydroxylations, to a maximum of three, seemed to increase
      activity within all of the groups. Before final decisions on SARs can be made,
      additional comparisons of the results of this subcellular assay (as an in vitro
      assay) with the results of in vivo assays should be made. Also, future
      investigations into the exact site of action within complex I and other possible
      sites of action (such as the NADH oxidase of plasma membranes) need to be
      conducted for a more. complete understanding of the utility and potential of this
      new group of very potent compounds.

PMID- 7586043
TI  - [Ultrasonic imaging of the anterior segment of the eye].
AB  - Our survey of the anterior segment of the eye by the ultrasound, is based in the
      usage of the Kitecko, the eye covering gadget, made by Laboratories 3M. The
      Kitecko opened a new possibilities for us in the localization of the intraocular,
      RTG noncontrast foreign bodies of the anterior segment, as well obscure optical
      medium.

PMID- 7586049
TI  - Hepatocyte injury resulting from the inhibition of mitochondrial respiration at
      low oxygen concentrations involves reductive stress and oxygen activation.
AB  - By correlating lactate/pyruvate ratios and ATP levels, cytotoxicity induced by
      the mitochondrial respiratory inhibitors or hypoxia:reoxygenation injury can be
      attributed not only to ATP depletion but also to reductive stress and oxygen
      activation. Thus hypoxia, cyanide or antimycin markedly increases reductive
      stress, non-heme Fe release and H2O2 formation in hepatocytes. Cytotoxicity was
      partly prevented with the ferric chelator desferoxamine, the xanthine oxidase
      inhibitor oxypurinol and the hydrogen peroxide scavenger glutathione. No lipid
      peroxidation could be detected and phenolic anti-oxidants had little effect.
      However, polyphenolic antioxidants or the superoxide dismutase mimics TEMPO or
      TEMPOL partly prevented cytotoxicity. Furthermore, increasing the hepatocyte
      NADH/NAD+ ratio with NADH generating compounds such as ethanol, glycerol, or beta
      hydroxybutyrate markedly increased cytotoxicity (prevented by desferoxamine) and
      further increased the intracellular release of non-heme iron. Cytotoxicity could
      be prevented by glycolytic substrates (eg. fructose, dihydroxyacetone,
      glyceraldehyde) or the NADH utilising substrates acetoacetate or acetaldehyde
      which decreased the reductive stress and prevented intracellular iron release.
      These results suggest that liver injury resulting from insufficient respiration
      involves reductive stress which releases intracellular Fe, converts xanthine
      dehydrogenase to xanthine oxidase and causes mitochondrial oxygen activation. The
      cell's antioxidant defences are compromised and ATP catabolism contributes to
      oxygen activation.

PMID- 7586051
TI  - Studies of the reaction of acetaldehyde with deoxynucleosides.
AB  - The reaction of acetaldehyde with deoxynucleosides was studied in buffered
      solutions at room temperature (22-24 degrees C) and neutral pH. Reaction products
      were obtained with all deoxynucleosides with the exception of thymidine, as shown
      by reversed-phase HPLC analysis. The order of reactivity was dGuo > dAdo > dCyd,
      for which three, two and one reaction products, respectively, were obtained. We
      report here data on the kinetics of the reactions, the stability of the adducts
      at physiological pH, product yields, UV-spectroscopic data at different pH
      values, and describe the synthesis, isolation and structural characterization by
      FAB/MS and NMR of the stable adducts of acetaldehyde with dGuo. Furthermore, the
      formation of adducts with dGuo by the cooperative reaction of Aa with ethanol was
      studied.

PMID- 7586050
TI  - Peroxisome proliferation and associated effects caused by perfluorooctanoic acid
      in vitamin A-deficient mice.
AB  - Vitamin A-deficient male mice were treated for 10 days with 0.02%
      perfluorooctanoic acid (PFOA) in their diet. The effects of this highly potent
      peroxisome proliferator on peroxisomal palmitoyl-CoA oxidation and lauroyl-CoA
      oxidase activities were reduced by 3.1-7.5 times in comparison to the values
      obtained with mice receiving a vitamin A-adequate diet. The activity of
      peroxisomal catalase was virtually unaffected by vitamin A deficiency and
      treatment with PFOA had no significant effect on this activity in vitamin A
      adequate or vitamin A-deficient mice. However, vitamin A deficiency itself caused
      a more than 800% increase in cytosolic catalase activity. Thus, the percentage
      increase caused by PFOA on cytosolic catalase activity was reduced 12.6 times in
      vitamin A-deficient mice compared to the increase in vitamin A-adequate mice,
      although the total absolute activities were similar. These findings suggest that
      the peroxisome proliferation caused by this peroxisome proliferator is highly
      dependent on the vitamin A status of the mouse.

PMID- 7586052
TI  - Time dependence of accumulation and binding of inorganic and organic arsenic
      species in rabbit erythrocytes.
AB  - The uptake by rabbit erythrocytes of 0.4 mM arsenate, As(V), monomethylarsinate,
      MMA(V) and dimethylarsonate, DMA(V) were compared over 24 h. In membrane-free
      hemolysate, the distribution of As between proteins (10 kDa) and ultrafiltrate
      was determined by ultrafiltration and arsenic species in the ultrafiltrate were
      identified by thin layer chromatography methods. 1H spin-echo Fourier transform
      NMR was used to follow the binding of these arsenic species to glutathione (GSH).
      31P-NMR was used to observe their effects on high-energy adenine nucleotide
      levels (ATP, ADP). These results demonstrate that As(III) readily accumulates in
      cells, reaches a quasi-plateau at 78% of the total As in the incubation after 1 h
      and 88% of the total As after 24 h. On average, 20% of the total erythrocyte
      As(III) burden is associated with the protein fraction, particularly with
      hemoglobin (Hb). About 68% of the erythrocyte As(III) burden is bound to GSH.
      As(III) has no effect on ATP levels during a 5-h incubation. By comparison, As(V)
      enters erythrocytes more slowly (53% of the total As after 5 h). Erythrocytes
      take up 81% of the As(V) in the reaction system after a 24 h incubation. Of the
      total As burden in As(V)-exposed erythrocytes, 22% was associated with the
      proteins (10 kDa) and possibly reduced to As(III) and 59% was in the
      ultrafiltrate (8% as As(III) and 51% as As(V)). This finding indicates that, over
      a 24 h incubation period, the reduction of As(V) to As(III) may account for 30%
      of the total As in rabbit erythrocytes. As(V) present in the erythrocytes enters
      the phosphate pool and depletes ATP. In comparison, about 65% of the total MMA(V)
      or about 44% of the total DMA(V) in the incubation system is taken up by rabbit
      erythrocytes during a 24 h incubation. Neither organoAs species perturbed the Hb
      signals observed by spin-echo Fourier transform NMR and the binding to GSH was
      minimal. Unlike As(V), MMA(V) and DMA(V) do not perturb phosphate metabolism,
      showing that, despite their pentavalent oxidation state, these arsenic species
      are not analogs for phosphate.

PMID- 7586053
TI  - Cytotoxicity of aromatic amines in rat liver and oxidative stress.
AB  - A possible role of oxidative stress in producing acute toxicity in rat liver by
      aromatic amines and nitroarenes was tested. Oxidative stress was assessed by
      measuring the excretion of oxidized glutathione (GSSG) into the bile in isolated
      perfused livers and in female Wistar rats with cannulated bile ducts. The liver
      perfusion system was calibrated with t-butylhydroperoxide (t-BH) and menadione.
      The minimal concentration in the perfusate of t-BH necessary to observe a
      significant effect was 18 microM for 5 min. It was calculated that rat liver is
      able to cope with an extra production of about 70 nmol GSSG per min and g liver
      before GSSG is excreted into bile. No effect was observed when 2-aminofluorene, 2
      acetylaminofluorene (AAF), trans-4-aminostilbene, and trans-4-acetylaminostilbene
      were added to the perfusate at 50 microM for 20 min. Moreover, 2-aminofluorene,
      trans-4-aminostilbene, 2-nitrofluorene and trans-4-nitrostilbene did not increase
      GSSG excretion when administered simultaneously with effective concentrations of
      t-BH. AAF was not acutely toxic, blood transaminases and lipid peroxidation were
      not increased with AAF doses as high as 1 mmol/kg. Since the dose rate of
      aromatic amines, like AAF, in feeding studies for tumor formation is about 100
      times below that examined in the isolated perfused livers, it is highly unlikely
      that oxidative stress is generated by metabolites able to undergo redox cycling
      and that reactive oxygen contributes to acute toxic effects.

PMID- 7586055
TI  - Synthesis and pharmacological activities of novel bicyclic thiazoline derivatives
      as hepatoprotective agents II. (7-Alkoxycarbonyl-2,3,5,6-tetrahydropyrrolo[2,1
      b]thiazol-3-ylidend) acetamid derivatives.
AB  - A series of exomethylenic bicyclic thiazoline derivatives (3a--i) was synthesized
      and evaluated for hepatoprotective activity against galactosamine-induced and
      monoclonal antibody-induced acute liver injuries in rats. The structure-activity
      relationships were investigated. Among the compounds synthesized, N-methyl-(7
      isopropoxy-carbonyl-6,6-dimethyl-2,3,5,6- tetrahydropyrrolo[2,1-b]thiazol-3
      ylidene)acetamide (3i) exhibited the most potent hepatoprotective activity. This
      compound suppressed galactosamine-induced hepatic injury at 100 mg/kg by oral
      administration and further prevented monoclonal antibody-induced hepatic injury
      at 30 mg/kg by intraperitoneal injection, as judged from the changes in serum
      transaminase activities.

PMID- 7586054
TI  - Fungal metabolites. XX. Effect of proline residue on the structure of ion-channel
      forming peptide, trichosporin B-VIa.
AB  - The secondary structures of an ion-channel-forming icosapeptaibol, trichosporin B
      VIa, and its Aib14-substituted derivative containing no Pro were investigated on
      the basis of CD and various NM experiments in methanol. Trichosporin B-VIa has a
      fully helical structure with a kink stabilized by a 1<--4 hydrogen-bond between
      the Leu12 CO and Val15 NH. The helical structure is composed of 3(10)-helix in
      the N-terminal first turn and the C-terminal moiety following Leu12, and alpha
      helix in the middle region. In contrast, the Aib14 derivative predominantly has a
      straight alpha-helical structure except for a 3(10)-helix region in the N
      terminal first turn.

PMID- 7586056
TI  - Structure-activity relationship study of TXA2 receptor antagonists. 4-[2-(4
      substituted phenylsulfonylamino)ethylthio]phenoxyacetic acids and related
      compounds.
AB  - We have recently reported that 4-[2-(4-substituted phenylsulfonylamino)
      ethylthio]phenoxyacetic acids and related compounds showed potent thromboxane A2
      (TXA2) receptor antagonist activity. To understand how substituents affect the
      biological activity, the quantitative structure-activity relationship (QSAR) was
      analyzed by using the Hansch-Fujita method for 36 compounds, including newly
      synthesized compounds. The positive coefficient for pi R and FR in the results of
      the QSAR study suggested that a hydrophobic an sigma electron-withdrawing
      substituent R at the para-position of the phenylsulfonyl moiety is required to
      improve the activity. Further, a substituent R which is long and moderately wide,
      was suggested to be preferable for the activity. The positive coefficients for pi
      X,Y,W-COOH and sigma Q(1)-(6) may indicate that the introduction of a hydrophobic
      and electron-withdrawing group on the benzene ring of the phenoxy acetic acid
      moiety enhances the activity. The length of the W-COOH moiety may also be
      important. On the other hand, the effect of the presence of methylene (n = 1) was
      not clear.

PMID- 7586057
TI  - Synthesis and structure-activity relationships of 4-amino-5-chloro-2
      ethoxybenzamides with six- and seven-membered heteroalicycles as potential
      gastroprokinetic agents.
AB  - A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b--f and 5--8 bearing six-
      and seven-membered heteroalicycles was prepared and evaluated for
      gastroprokinetic activity. Compounds 3b--e, derived by replacement of the
      morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5- chloro-2
      ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally
      exhibited a potent gastric emptying activity. N-(4-Benzyl-3
      morpholinyl)methylbenzamide (5a) and its analogues 5b--e had weaker activity.
      However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a.
      Benzamides 6a--e, having seven-membered heteroalicycles, showed fairly potent
      activity. Molecular superimpositions of 5a, 6a and 8 upon 3a using computer
      graphics suggested that the direction of the N-benzyl group greatly influences
      the gastric emptying activity, whereas the location of the alicyclic nitrogen is
      less critical.

PMID- 7586060
TI  - Structures of toxic steroidal saponins from Narthecium asiaticum MAXIM.
AB  - The full structures of the two steroidal saponins from Narthecium asiaticum
      MAXIM. We previously identified as toxic substances by monitoring the toxicity in
      guinea pigs were phytochemically reinvestigation on the aerial parts of the
      plant. The desired toxic saponins (6,7) were isolated together with two known
      lignan glucosides (1,2), a known flavonoid glucoside (3), a new furanone
      glucoside (4), a known steroidal saponin (5) and a new steroidal saponin (8). The
      structures of the new furanone glucoside, toxic saponins and new saponin were
      determined on the basis of spectroscopic data and acid- or enzymatic-catalyzed
      hydrolysis to be (S)-5-beta-D-glucopyranosyloxy-4-methoxyfuran-2(5H)-one (4),
      (25R,S)-5 beta-spirostan-3 beta-ol 3-O-[O-beta-D-glucopyranosyl-(1-->2)-] O
      [alpha-L-arabinopyranosyl-(1-->3)]-beta-D-galactopyranoside] (6), (25R,S)-5 beta
      spirostan-3 beta-ol 3-}O[O-beta-D-glucopyranosyl-(1-->2- O-[beta-D-xylopyranosyl
      (1-->3)]-beta-D-galactopyranoside] (7) and (24S,25R)-5 beta-spirostan-3 beta,24
      diol 3-O-[O-beta-D- glucopyranosyl-(1-->2)-O-]alpha-L-arabinopyranosyl-(1-->3)]
      beta-D - galactopyranoside] (8), respectively.

PMID- 7586059
TI  - Structure-activity relationships of neuromedin U. II. Highly potent analogs
      substituted or modified at the N-terminus of neuromedin U-8.
AB  - To develop a highly potent agonist and to examine the structure-contractile
      activity relationship of neuromedin U-8(NMU-8), seventeen analogs were
      synthesized and tested for contractile activity on isolated chicken crop smooth
      muscle preparations. The analogs were designed to examine the contributions of
      cyclic structure and acidic function at the N-terminal of NMU-8 and NMU-8(2--8)
      to the biological activity. The relative activity (RA) values of NMU-8 analogs
      were as follows: [Dp-Glu1]-NMU-8,5.50; [pyrohomoglutamyl(pHgu)1]-NMU-8,4.65;[D
      pHgu1]-NMU-8, 4.66; [Asp1]-NMU-8, 11.4; [acetyl(Ac)-Asp1]-NMU-8, 9.81; [Ac-Glu1]-
      NMU-8, 18.6; [succinyl (Suc)-Tyr1-NMU-8,69.3; [3-sulfoalanyl (Sal)1]-NMU-8, 12.7.
      The RA values of NMU-8(2--8) analogs were as follows: alpha-picolinyl (Pic)-NMU-8
      (2--8), 7.96; 2-furoyl (Fur)-NMU-8, (2--8), 9.91; 2-thiophenecarboxyl (Thi)-NMU-8
      (2--8), 3.41; 4-hydroxyphenylpropionyl (Hpp)-NMU-8(2--8), 3.20; o-phthalyl (Pht)
      NMU-8 (2--8), 11.3; Suc-NMU-8 (2--8), 109; malonyl (Mlo)-NMU-8 (2--8), 17.9;
      maleyl (Mle)-NMU-8 (2--8), 31.6; glutaryl (Glt)-NMU-8 (2--8), 81.3; The potencies
      of the analogs were higher than that of p-NMU-8. Suc-NMU-8 (2--8) showed the
      highest potency among the analogs synthesized. The results reveal that the
      carboxylic acid group at the N-terminus of NMU-8 makes a major contribution to
      the activity.

PMID- 7586058
TI  - Structure-activity relationships of neuromedin U. I. Contractile activity of dog
      neuromedin U-related peptides on isolated chicken crop smooth muscle.
AB  - Synthetic dog neuromedin U-25(d-NMU-25), U-8(d-NMU-8) and their fragments wer
      examined for contractile activity on chicken crop smooth muscle preparation. The
      relative activities of d-NMU-25, d-NMU-25(15--25)NH2 and d-NMU-8 to porcine
      neuromedin U-8 (p-NMU-8) were 1.69, 2.54 and 5.78, respectively. High activity of
      d-NMU-8 may be attributable to the N-terminal pGlu residue, which provides
      resistance to aminopeptidases. Various NMU-8 analogs, having various amino acids,
      N alpha-acetylated amino acids, D-amino acids, or simple organic acids at
      position 1, were synthesized and evaluated for contractile activity. None of the
      substitutions caused a significant decrease of the biological activity.
      Modification at the N-terminal to give aminopeptidase resistance produced analogs
      with increased contractile activity, presumably because they were not degraded by
      soluble enzymes released into the bioassay fluid from isolated chicken crop
      tissue.

PMID- 7586061
TI  - Cytotoxic limonoids and tetranortriterpenoids from Melia azedarach.
AB  - The ethanolic extract of the root bark of Melia azedarach exhibited cytotoxic
      activity against lymphocytic leukemia P388 cell lines in vitro. Systematic
      fractionation of the extract monitored by cytotoxic bioassay led to the isolation
      of two new azadirachtin-type limonoids, 1-tigloyl-3-acetyl-11
      methoxymeliacarpinin (1) and 1-acetyl-3-tigloyl-11-methoxymeliacarpinin (2),
      together with three highly cytotoxic sendanin-type limonoids, 29-isobutylsendanin
      (3), 12-hydroxyamoorastin (4) and 29-deacetylsendanin (5). The acetylated
      derivatives of 4 also underwent cytotoxic bioassay.

PMID- 7586063
TI  - Protein chemotaxonomy of genus Datura. IV. Amino acid sequence of Datura
      ferredoxins depends not on the species but the section of Datura plants from
      which it comes.
AB  - The complete amino acid sequences of [2Fe-2S] ferredoxins from Datura quercifolia
      (section Stramonium) and D. fastuosa (section Dutra) have been determined by
      automated Edman degradation of the entire Cm-protein and of the peptides obtained
      by tryptic digestion and CNBr treatment. The D. quercifolia and D. fastuosa
      ferredoxins exhibited identical amino acid sequences to D. stramonium (section
      Stramonium) and D. metal (section Dutra) ferredoxins, respectively. This result
      suggests that the amino acid sequence of Datura ferredoxins depends on the
      section but not the species of Datura plants.

PMID- 7586062
TI  - Oleanene-type triterpene glycosides from Puerariae Radix. II. Isolation of
      saponins and the application of tandem mass spectrometry to their structure
      determination.
AB  - A continuing study of the ingredients of Puerariae Radix, the roots of Pueraria
      lobata (WILLD.) OHWI, which is one of the most important crude drugs, has
      resulted in the first isolation of four new oleanene-type triterpene glycosides,
      named kudzusaponins SA1, SA2, SA3 and C1 (1-4). Their structures were determined
      to be 3-O-beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl soyasapogenol
      A (1), 3-O-beta-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl soyasapogenol
      A 22-O-alpha-L-arabinopyranoside (2), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      galactopyranosyl-(1-->2)-D- glucuronopyranosyl kudzusapogenol C 21-O-beta-D
      glucopyranoside (4), respectively. The usefulness of tandem mass spectrometry in
      the structural determination of oleanene-type triterpene bisdesmosides is also
      discussed.

PMID- 7586064
TI  - Steroidal saponins from the underground parts of Hosta longipes and their
      inhibitory activity on tumor promoter-induced phospholipid metabolism.
AB  - Phytochemical study on the underground parts of Hosta longipes gave six new
      steroidal saponins together with a known one. The structures of the new compounds
      were determined by detailed analysis of their 1H- and 13C-NMR spectra including
      two-dimensional NMR spectroscopy, acid-catalyzed hydrolysis followed by chemical
      correlation, and by comparison with spectral data of known compounds. The
      isolated saponins and their aglycones were examined for inhibitory activity on 12
      O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P-incorporation into
      phospholipids of HeLa cells to identify new antitumor-promoter compounds.

PMID- 7586066
TI  - Rhodiocyanosides A and B, new antiallergic cyanoglycosides from Chinese natural
      medicine "si lie hong jing tian", the underground part of Rhodiola quadrifida
      (Pall.) Fisch. et Mey.
AB  - Two new antiallergic cyanoglycosides named rhodiocyanosides A and B were isolated
      from the Chinese natural medicine "Si Lie Hong Jing Tian" (Shiretsukoukeiten in
      Japanese), the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey.,
      together with two new glycosides, octyl alpha-L-arabinopyranosyl(1-6)-beta-D
      glucopyranoside and gossypetin 7-O-beta-D-glucopyranosyl(1-3)-alpha-L
      rhamnopyranoside. Their chemical structures were determined on the basis of
      chemical and physicochemical evidence. Rhodiocyanosides A and B exhibited
      inhibitory activity on the histamine release from rat peritoneal exudate cells
      sensitized with anti-DNP IgE. In addition, rhodiocyanoside A was found to inhibit
      the PCA reaction in rats.

PMID- 7586067
TI  - A novel 16,23-epoxy-5 beta-cholestane glycoside with potent inhibitory activity
      on proliferation of human peripheral blood lymphocytes from Ornithogalum
      saundersiae bulbs.
AB  - A novel 16,23-epoxy-5 beta-cholestane triglycoside (1) was isolated from the
      bulbs of Ornithogalum saundersiae (Liliaceae). The structure was determined by
      extensive spectroscopic analysis. The conformation of the E-ring part of 1 was
      studied through molecular mechanics and molecular dynamics calculation methods.
      Compound 1 potently inhibited proliferation of peripheral blood lymphocytes
      provided from a chronic renal failure patient without causing any cytotoxicity in
      the lymphocytes and HL-60 human leukemia cells.

PMID- 7586069
TI  - Chemical constituents of Chinese natural medicine, morindae radix, the dried
      roots of morinda officinalis how.: structures of morindolide and
      morofficinaloside.
AB  - A new iridoid lactone, morindolide, and a new iridoid glucoside,
      morofficinaloside, have been isolated from a Chinese natural medicine, Morindae
      Radix, the dried root of Morinda officinalis How. together with a number of known
      compounds: five anthraquinones, four iridoid glucosides, a monoterpene glycoside,
      two sterols, an ursane-type triterpene, and a lactone compound. The chemical
      structures of the new compounds were determined on the basis of chemical and
      physicochemical evidence.

PMID- 7586068
TI  - Syntheses of three interglycosidic isomers of N-acetyl-beta-D-mannosaminyl-L
      rhamnoses associated with O-antigens of several gram-negative opportunistic
      pathogens.
AB  - We achieved practical, highly stereoselective syntheses of three interglycosidic
      isomers of N-acetyl-beta-D-mannosaminyl-L-rhamnoses, among which a beta(1-->4)
      isomer corresponds to the repeating unit of the O-antigen of lipopolysaccharide
      (LPS) from the opportunistic pathogens Pseudomonas cepacia O5 and Pseudomonas
      aeruginosa X (Meitert). The other isomers are a beta(1-->2)-disaccharide, a
      constituent of LPS from Escherichia coli O1A, and an artificial beta(1-->3)
      isomer. The disaccharides were obtained by simple three-step reaction sequences
      from 2-(benzoyloxyimino)-2-deoxyglycosyl halides (mannosamine progenitor). beta
      Selective glycosylations of appropriately protected L-rhamnosyl acceptors were
      performed. Subsequent reduction of the 2-acyloxyimino function to an amino group,
      N-acetylation, and removal of the protecting groups provided the target
      disaccharides. 13C-NMR and nuclear Overhauser effect spectra proved to be useful
      for structural determination of the positional isomers of the disaccharides.

PMID- 7586065
TI  - Studies on pyridonecarboxylic acids. IV. Synthesis and antibacterial activity
      evaluation of S-(-)- and R-(+)-6-fluoro-1-methyl-4-oxo-7- (1-piperazinyl)-4H
      [1,3] thiazeto[3,2-a]quinoline-3-carboxylic acids.
AB  - Optically active isomers of 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H- [1,3]
      thiazeto [3,2-alpha] quinoline-3- carboxylic acid (NM394, 3) were prepared
      through optical resolution of their racemic intermediate ( +/- )-1 by high
      performance liquid chromatography (HPLC). The absolute configuration at the C-1
      position in the thiazeto-quinolone ring of ( - )-3 was confirmed by X-ray
      analysis ( - )-4 to be S. The in vitro antibacterial activity of ( - )-3 was 2--8
      times that of (+)-3.

PMID- 7586070
TI  - Studies on cognitive enhancing agents. I. Antiamnestic and antihypoxic activities
      of 2-dimethylaminoethyl ethers and related compounds.
AB  - N-(2-Dimethylaminoethyl)carboxamide (1a-d), 2-dimethylaminoethyl alkyl ether (2a,
      b), and 2-dimethylaminoethyl 2-hydroxy-2-phenethyl ether (3a-c) and its amino and
      methylene analogues (3d, 4) have been screened for antiamnestic and antihypoxic
      activities in mice. A clear reversing effect on electroconvulsive shock-induced
      amnesia was found with 1a-d, 2a,b, and 2-dimethylaminoethyl 2-hydroxy-2
      phenylethyl ether (3a). However, a protective effect against hypoxia was only
      observed with 3a. Compound 3a, which displayed the dual activity, was further
      investigated for ameliorating effect on CO2-induced memory impairment, and it was
      found to be more potent than indeloxazine and bifemelane. In addition, the acute
      toxicity of 3a in mice was significantly lower than that of tacrine, but its
      serum-to-brain penetration ability in rats was less than that of the reference
      drugs.

PMID- 7586071
TI  - Studies on cognitive enhancing agents. II. Antiamnestic and antihypoxic
      activities of 1-aryl-2-(2-aminoethoxy)ethanols.
AB  - A series of 2-(2-aminoethoxy)-1-phenylethanols having a variety of N- and phenyl
      substitution patterns as well as 5- and 6-membered heteroaryl counterparts of our
      prototype compound 1 (2-(2-dimethylaminoethoxy)-1-phenylethanol) have been
      prepared and evaluated for antiamnestic and antihypoxic activities. Compound 3b,
      the 3-methylphenyl analogue of 1, proved to be significantly more potent than 1
      in reversing electroconvulsive shock-induced amnesia as well as CO2-induced
      learning-impairment in mice. It exhibited low acute toxicity in mice and afforded
      a greater brain/serum concentration ratio than 1 after oral administration to
      rats.

PMID- 7586073
TI  - Studies on cerebral protective agents. VIII. Synthesis of 2-aminothiazoles and 2
      thiazolecarboxamides with anti-anoxic activity.
AB  - Various 2-aminothiazoles (2a-s and 3a-g) and 2-thiazolecarboxamides (4a-h),
      possessing a nitrogenous basic moiety at the C-2 position of the thiazole ring,
      were prepared and tested for anti-anoxic (AA) activity in mice. Among them, N-[2
      (4-morpholinyl)ethyl]-4-(3-trifluoromethylphenyl)-2- thiazolecarboxamide
      hydrochloride (4e, FR108143) (minimum effective doses of 3.2 mg/kg i.p. and 10
      mg/kg p.o., respectively) exhibited more potent AA activity than either FK360 or
      compound 1, each of which has a nitrogenous basic moiety at the C-5 position. The
      structure-activity relationships with regard to AA activity of this series of
      compounds are discussed, and the three-dimensional electrostatic potentials (3D
      MEP) around the basic nitrogen atom of FK360 and the thiazole derivative (4e) are
      compared.

PMID- 7586072
TI  - Studies on cognitive enhancing agents. III. Antiamnestic and antihypoxic
      activities of a series of 1-bicycloaryl-2-(omega-aminoalkoxy)ethanols.
AB  - 2-(2-Aminoethoxy)-1-hydroxyethyl derivatives of bicyclic arenes (naphthalene,
      thianaphthene, benzofuran, and indole) were prepared and screened for
      antiamnestic (AA) and antihypoxic (AH) activities which were evaluated by
      measuring the reversing potency in electroconvulsion-induced amnesia and the
      protective effect against hypoxia, respectively, in mice. Compound 3o, 1
      (benzo[b]thiophen-5-yl)-2- (2-diethylaminoethoxy)ethanol, showed the best AA and
      AH activity profile, being superior to our prototype compound, 2-(2
      dimethylaminoethoxy)-1-phenylethanol (1). Elongation of the ethylene linkage in
      the side chain of 3o to 3- and 4-carbon moieties brought about a significant
      decrease in AH activity. Compound 3o was further investigated for its protective
      effect against CO2-induced memory impairment and for acute toxicity in mice. It
      is ten-fold more potent than tacrine in the amnesia-reversal assay and is
      considerably less toxic than tacrine.

PMID- 7586075
TI  - Synthetic studies on condensed-azole derivatives. III. Synthesis and anti
      asthmatic activities of C-substituted alkyl side chain derivatives of omega
      sulfamoylalkylthioimidazo[1,2-b]pyridazines and related compounds.
AB  - A series of novel alkylthioimidazo[1,2-b]pyridazines was synthesized and
      evaluated for ability to inhibit platelet activating factor (PAF)-induced
      bronchoconstriction in guinea pigs. Among them, 3-(imidazo[1,2-b]pyridazin-6
      yl)thio-2,2-dimethylpropanesulfona mide (15) showed the most potent inhibitory
      effect. The structure-activity relationships in this series of compounds, in
      particular, the effects of conversion of the imidazopyridazine ring into other
      heterocyclic rings, introduction of a substituent group at the 2 or 3 position of
      the imidazopyridazine ring and introduction of a substituent group into the alkyl
      side chain, are also discussed.

PMID- 7586074
TI  - Synthetic studies on condensed-azole derivatives. I. Synthesis and anti-asthmatic
      activities of omega-substituted alkylthioimidazo[1,2-b]pyridazines.
AB  - A series of novel omega-substituted alkylthioimidazo[1,2-b]pyridazines was
      designed and synthesized in an effort to find a novel anti-asthmatic agent. The
      anti-asthmatic activity of these compounds was evaluated on the basis of their
      ability to inhibit thromboxane A2 synthetase and platelet activating factor (PAF)
      induced bronchoconstriction in guinea pigs. None of these compounds significantly
      inhibited thromboxane A2 synthetase, though, sulfonamide derivatives potently
      inhibited PAF-induced bronchoconstriction. Among them, 3-(imidazo[1,2-b]pyridazin
      6-yl)thiopropanesulfonamide (5) showed the most potent inhibitory effect. The
      anti-asthmatic effects of compound 5 in experimental models were superior to
      those of theophylline.

PMID- 7586078
TI  - Synthesis of ganglioside GM3 and GM4 analogs having mimics of ceramide moieties
      and their binding activities with influenza virus A.
AB  - Ganglioside GM4 (1) and GM3 (2) analogs, which contain mimics of the ceramide
      moieties of gangliosides, were synthesized. The syntheses of 1 and 2 feature
      stereoselective glycosylation of methyl (phenyl 5-acetamido-4,7,8,9-tetra-O
      acetyl-3,5-dideoxy-2-thio-beta-D- galacto-2-nonulopyranosid)onate (10) as the
      sialosyl donor with suitably protected galactose and lactose acceptors catalyzed
      by N-bromosuccinimide (NBS), iodine, and tetrabutylammonium
      trifluoromethanesulfonate (TBAOTf) as the glycosyl promoter in acetonitrile under
      kinetically controlled conditions. Compound 2 exhibited binding activity towards
      influenza virus A.

PMID- 7586077
TI  - Synthesis and antitumor activity of duocarmycin derivatives.
AB  - A series of duocarmycin B2 derivatives, modified at the phenolic hydroxyl group
      to ester, carbonate and carbamate, was synthesized. Antitumor activity of these
      analogs was preliminarily evaluated by assays of growth inhibition of HeLa S3
      cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The
      stability of the compounds under aqueous conditions was examined, and we found a
      correlation between antitumor activity in vivo and stability in aqueous solution,
      that is, the more stable derivatives exhibited higher antitumor activity. Among
      these derivatives, the N,N-dialkylcarbamoyl analogs exhibited both improved
      antitumor activity and higher stability compared with duocarmycin B2. These
      analogs were subjected to further biological evaluation and they expressed broad
      spectrum activity toward murine solid tumors M5076, Colon 26 and Colon 38, and
      human xenografted carcinoma MX-1.

PMID- 7586079
TI  - Synthesis and enantioselectivity of optically active 1- and 3-substituted 4
      phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols and related compounds as
      norepinephrine potentiators.
AB  - Optically active 1,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (1R,4R
      3a and 1S,4S-3b, 1S,4R-4a, and 1R,4S-4b) and 2-methyl-4-phenyl-1,2,3,4
      tetrahydroisoquinolines (4S-5a and 4R-5b) were prepared in order to examine the
      effects of the 1-, 3-, and 4-substituents of 2-methyl-4-phenyl- 1,2,3,4
      tetrahydroisoquinolin-4-ol (PI-OH) (1) on the enantioselectivity for
      norepinephrine (NE) potentiating activity. The conformations and absolute
      configurations of 3-5 were determined from their 1H-NMR and circular dichroism
      (CD) spectra and by single-crystal X-ray diffractometric analysis. The NE
      potentiating activity of the optically active 3-5 and previously prepared 3
      methyl derivatives (3R,4R-6a and 3S,4S-6b) of PI-OH were tested. The results show
      that compounds 3, 4, and 6 had high enantioselectivity for NE potentiation: the
      4R series of the enantiomers exhibited activity but not the 4S-enantiomers. The
      activity of the 4-desoxy compound 5 also resided exclusively in the 4S
      enantiomer. These findings suggest the presence of a specific receptor for NE
      uptake, and the enantiomers 3a, 4a, 5a, and 6a may be antagonistic at this NE
      uptake receptor.

PMID- 7586076
TI  - Synthesis and structure-activity studies of a series of 1-oxa-2,8
      diazaspiro[4.5]decan-3-ones and related compounds as M1 muscarinic agonists.
AB  - A series of novel 2,8-dialkyl-1-oxa-2,8-diazaspiro[4.5]decan-3-ones and 2,8
      dimethyl-1,2,8-triazaspiro[4.5]-decan-3-one (13), related to M1 muscarinic
      agonists YM796 and RS86, were synthesized by using Michael addition reaction of
      hydroxyurea or methylhydrazine to alpha, beta-unsaturated esters followed by
      cyclization reaction. These compounds were assessed for binding affinities for M1
      and M2 receptors and in vivo muscarinic activity: namely, amelioration of
      scopolamine-induced impairment in rat passive avoidance tasks and induction of
      hypothermia, tremor, and salivation. 2,8-Dimethyl-1-oxa-2,8-diazaspiro[4.5]decan
      3-one (6a) exhibited high affinities for both M1 and M2 receptors, showed
      antiamnesic activity (0.1 mg/kg, s.c.) and induced hypothermia (3 mg/kg, s.c.).
      In addition, 6a stimulated phosphoinositide hydrolysis in rat hippocampal slices,
      indicating partial agonistic activity for M1 muscarinic receptors. The alteration
      of the methyl group at N2 of 6a increased the selectivity in binding affinities
      for M1 over M2 receptors, but resulted in loss of M1 agonistic activity or
      antiamnesic activity. Compound 13 exhibited only low affinity for M1 receptors,
      suggesting that a basic nitrogen atom is not tolerated in M1 receptor binding as
      a substitute for an oxygen atom or a carbonyl group at the 1-position of 6a or
      RS86. None of these derivatives exhibited high selectivity for antiamnesic effect
      over induction of hypothermia compared to YM796.

PMID- 7586081
TI  - Synthesis of 19-hydroxylated bile acids and identification of 3 alpha,7 alpha,12
      alpha,19-tetrahydroxy-5 beta-cholan-24-oic acid in human neonatal urine.
AB  - The synthesis of 19-hydroxylated bile acids (3 alpha,19-dihydroxy-, 3 alpha,7
      alpha,19-trihydroxy-, 3 alpha,12 alpha,19-trihydroxy- and 3 alpha,7 alpha,12
      alpha,19-tetrahydroxy-5 beta-cholan-24-oic acids) was described. These
      synthesized 19-hydroxylated bile acids were used as standard samples for the
      analysis of bile acids in human urine by gas chromatography-mass spectrometry. 3
      alpha,7 alpha,12 alpha,19-Tetrahydroxy-5 beta-cholan-24-oic acid was identified
      in neonatal urines (0.1-1.5 micrograms/ml and 1.5-7% of total bile acids).

PMID- 7586080
TI  - Synthesis and opioid activities of [D-Leu-8]Dynorphin(1-8) analogs containing a
      reduced peptide bond, psi(CH2-NH).
AB  - [D-Leu8]Dynorphin(1--8)-NH2 analogs, in which each peptide bond was
      systematically replaced with a psi(CH2NH) peptide bond, were synthesized by the
      solid-phase method. The psi(CH2NH) bond was introduced by the Boc-amino acid
      aldehyde/NaCNBH3 method on a solid support. In the syntheses of the analogs,
      undesirable double alkylation took place at the sequences of Tyr1 psi(CH2NH)Gly2
      and Gly2 psi(CH2NH)Gly3, possibly due to the low steric hindrance of the glycine
      residue. To suppress the double alkylation, a minimum amount of aldehydes was
      employed. In the receptor binding assay, the psi(CH2NH) replacement of N-terminal
      peptide bonds which led to 1 psi 2-(2) and 2 psi 3-analogs (3) resulted in a
      marked reduction in binding affinities for mu-, delta-, and kappa-opioid
      receptors, while that of the other peptide bonds afforded analogs with a high
      kappa-receptor affinity. A 3 psi 4-analogs (4) showed extremely high kappa
      receptor selectivity (mu/kappa Ki ratio = 339, delta/kappa Ki ratio = 24104). In
      the in vitro bioactivity assay (guinea pig ileum assay), 2 showed a very low IC50
      ratio (2.0) in the presence and absence of peptidase inhibitors whereas those of
      other analogs were >27, suggesting that the introduction of the CH2NH isostere at
      Tyr1-Gly2 greatly enhanced the enzymatic stability of the parent peptide.
      Furthermore, analogs 2 and 3 showed a very low sensitivity to the inhibitory
      effect of NaCl plus 5'-guanylylimidodiphosphate on their binding at a kappa
      receptor site as compared with the other analogs and the parent peptide. These
      results suggest that the two analogs (2 and 3) have partial kappa-antagonist
      properties.

PMID- 7586082
TI  - Five new C-methyl flavonoids, the potent aldose reductase inhibitors from
      Matteuccia orientalis Trev.
AB  - Five new compounds, matteuorien, matteuorienin, and matteuorienate A (7), B (8),
      and C (9) were isolated together with five known compounds from the MeOH extract
      of the rhizome of Matteuccia orientalis Trev. The structures of these compounds
      were determined by the use of spectroscopic methods including two dimensional
      (2D)-NMR experiments and chemical methods, except for the configuration at the C
      3"' of matteuorienate A (7), B (8), and C (9). Among them, matteuorienate A, B,
      and C showed very strong aldose reductase inhibitory activity. A structure
      activity relationship study showed that a carboxyl group played an important part
      in aldose reductase inhibitory activity in these three compounds.

PMID- 7586084
TI  - Optimization of preparative conditions for polylactide (PLA) microspheres
      containing ovalbumin.
AB  - Polylactide (PLA) microspheres containing ovalbumin (OVA) as a model protein were
      prepared by a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method.
      The optimization of preparative parameters for the PLA microspheres containing
      OVA were performed, and the in vitro characteristics of the obtained microspheres
      were examined. Firstly, a smaller internal aqueous phase volume was found to be
      advantageous in obtaining high loading efficiency. Secondly, the addition of 2
      10% (w/v) NaCl into the external aqueous phase (0.5% (w/v) polyvinyl alcohol
      solution) also improved OVA loading efficiency. Prepared products showed a sharp
      release of OVA at the initial phase, but the following phase was characterized by
      a slow release rate of OVA that continued at least 28 d. The release rate of OVA
      from microspheres made of PLA with a molecular weight of 15400 was faster than
      that from microspheres made of PLA with a molecular weight of 58300. However, the
      LA/GA (lactide/glycolide) ratio was not likely to have much effect on the release
      profile of OVA. Finally, the effect of PLA microsphere particle size on the
      release profiles of OVA was examined. The extent of burst release at the initial
      phase increased as the mean diameter of prepared PLA microspheres decreased. For
      example, the PLA microspheres with a small mean diameter (5.0 microns) showed a
      40% burst release, but almost 30% of OVA remained in the PLA microspheres
      (confirmed by HPLC method) after the 28 d release test, suggesting the
      possibility of using this carrier as a long-acting protein delivery system.

PMID- 7586083
TI  - Studies on differentiation inducers. V. Steroid glycosides from periplocae
      radicis cortex.
AB  - Six pregnane glycosides and three cardenolides were isolated as differentiation
      inducers using mouse myeloid leukemia (Ml) cells from Periplocae Radicis Cortex
      (bark of Periploca sepium BGE., Asclepiadaceae). The cardenolides showed much
      higher activities than the pregnane glycosides. Besides these nine compounds,
      commercially available cardenolides were tested for their differentiation
      inducing activities using Ml cells. Digitoxin and digoxin induced Ml cells into
      phagocytic cells, but others did not. In the presence of 1 nM of actinomycin-D,
      the activity of steroid glycosides was enhanced against Ml cells.

PMID- 7586085
TI  - The inhibitory effect of the crude extract from a seaweed of Dygenea simplex C.
      Agardh on the in vitro cytopathic activity of HIV-1 and it's antigen production.
AB  - The crude water extract (NS-1) from a seaweed (Digenea simplex C. Agardh
      Rhodomelaceae) exhibited anti-human immunodeficiency virus (HIV)-1 activity in
      vitro. The inhibitory effect of the extract on the cytopathic activity of HIV-1
      and it's antigen production was examined using a microplate method,
      immunofluorescent assay, and an HIV antigen detection kit (Abbott). NS-1
      inhibited both the cytopathic effect of HIV-1 to MT-4 cells and the giant cell
      formation of Molt-4 cells infected with HIV-1.

PMID- 7586086
TI  - Studies on the preparation of bioactive lignans by oxidative coupling reaction.
      VI. Oxidation of methyl (E)-3-(4,5-dihydroxy-2-methoxyphenyl)-2-butenoate and
      lipid peroxidation-inhibitory effects of the produced caffeoquinone.
AB  - Oxidation of hydroxy-alpha-methylcinnamate 5 derived from 4-methylesculetin
      afforded the alpha-methylcaffeoquinone derivative 7 without formation of the
      oxidative coupling product. The reaction of the alpha-methylferulate derivative
      13 afforded a complex mixture of products. Thus, the hydroxy-alpha
      methylcinnamates seem not to be suitable substrates for oxidative coupling.
      Compound 7 was tested for inhibitory effect on lipid peroxidation. It showed more
      potent activity than idebenone in rat brain homogenate, and was much more potent
      than (+/-)-alpha-tocopherol in rat liver microsomes.

PMID- 7586087
TI  - Improved total synthesis and structure-activity relationship of arenastatin A, a
      potent cytotoxic spongean depsipeptide.
AB  - An efficient asymmetric synthesis of a cyclic depsipeptide arenastatis A (1) is
      described. 1, isolated from the marine sponge Dysidea arenaria, exhibited
      extremely potent cytotoxicity with IC50 of pg/ml for KB cells, and in this
      context the structure-activity relationship among several stereoisomers of 1 and
      allied compounds has also been examined.

PMID- 7586088
TI  - Detection of short-chain alpha-hydroxyaldehydic compounds as
      pentafluorbenzyloxime derivatives in bovine liver.
AB  - Pentafluorbenzyloxime derivatization allows fast, gentle and unambiguous
      identification of alpha-hydroxyaldehydic lipid peroxidation products via GC/MS in
      biological material. Even 1.5 g of a bovine liver sample is sufficient to detect
      short-chain 2-hydroxyalkanales resulting from cleavage reactions of dioxygenated
      fatty acids. Quantification is achieved after secondary derivatization with N
      methyl-N-t-butyldimethylsilyltrifluoracetamide (M-t-BSTFA) by mass spectrometry
      using characteristic ion traces of the derivatives. In addition, the
      corresponding (n-1)-hydroxy-n-oxo acids, previously unknown in biological
      material, could be detected.

PMID- 7586090
TI  - Mass spectrometric evidence for the anomalous chemical behavior of 11
      dehydrothromboxane B2.
AB  - When we subjected 11-dehydrothromboxane B2 (11-DTXB2), a metabolite of
      arachidonic acid, to standard chemical derivatization procedures we obtained a
      mixture of several products. Separation of the components was carried out by gas
      chromatography and their identification was accomplished through the study of
      their mass spectra, which are presented here. Anomalous behaviors include
      methylation of allylic and alcoholic hydroxyl groups by diazomethane, unusually
      slow derivatization of one of the hydroxyl groups with N,O-bis(trimethylsilyl)
      trifluoroacetamide (BSTFA) and etherification of another with ethanol. The
      underlying causes of these abnormal behaviors are not obvious, but appear to be
      related, at least in part, to the opening/closure of a lactone ring in the
      molecule. These observations have some bearing on the development of valid
      procedures for GC-MS quantification of this important marker of thromboxane A2
      synthesis in vivo, and of similar compounds.

PMID- 7586091
TI  - Aggregation properties of semisynthetic GD1a ganglioside
      (IV3Neu5AcII3Neu5AcGgOse4Cer) containing an acetyl group as acyl moiety.
AB  - GD1a ganglioside containing an acetyl group as acyl moiety, GD1a(acetyl), was
      synthesized from natural GD1a. The aggregative properties in aqueous solution of
      GD1a(acetyl) have been studied by static and dynamic laser light-scattering
      measurements. GD1a(acetyl) spontaneously aggregates as small micelles showing a
      hydrodynamic radius and molecular mass of 33 A and 96 kDa, respectively. Vibrio
      cholerae sialidase showed a very high activity on the micelles of GD1a(acetyl),
      compared to GD1a. This has been explained as a consequence of the high surface
      curvature of the the small micelles. High resolution proton NMR spectra were
      recorded from micelles of GD1a(acetyl) in deuterated water. The low overall
      correlation time of the GD1a(acetyl) micelles was calculated to be about 2 x 10(
      8)s, a value one order of magnitude lower than that determined for natural GD1a.

PMID- 7586089
TI  - Delay of copper-catalyzed oxidation of low density lipoprotein by in vitro
      enrichment with choline or ethanolamine plasmalogens.
AB  - Low density lipoprotein (LDL) isolated from human serum of different donors was
      enriched with plasmalogens and their diacyl analogs in order to investigate a
      possible effect of these phospholipids on the rate of lipid peroxidation in this
      lipoprotein. LDL was incubated with either vesicles of choline plasmalogen or
      phosphatidylcholine in presence of lipoprotein- deficient serum, or with
      liposomes of ethanolamine plasmalogen or phosphatidylethanolamine together with
      the non-specific phospholipid transfer protein isolated from beef liver. After re
      isolation of LDL by ultracentrifugation, a dose-dependent incorporation of the
      exogenous phospholipids was obtained. Enrichment of LDL with choline plasmalogen
      resulted in a delay of the copper-catalyzed oxidation of LDL from five different
      donors. LDL from two donors was also enriched with diacylglycerophosphocholine
      which led to a delay of oxidation, but the protective effect was smaller than
      with choline plasmalogen. Enrichment of LDL from two additional donors with
      ethanolamine plasmalogen resulted in the strongest protection against oxidation,
      whereas, diacylglycerophospho-ethanolamine had little effect. The delay of the
      copper-catalyzed LDL oxidation may be due to a direct antioxidative action of the
      plasmalogens, which are partially degraded during the lag phase of oxidation, or
      to an indirect effect caused by alteration of the LDL surface in the presence of
      an excess of glycerophospholipids.

PMID- 7586092
TI  - Method for measuring the activities of cholesteryl ester transfer protein (lipid
      transfer protein).
AB  - A continuous recording fluorescence assay was developed for cholesteryl ester
      transfer protein (CETP). The assay measures the increase in fluorescence
      accompanying the relocation of fluorescent lipids, cholesteryl esters and
      triglycerides, from a donor emulsion to an acceptor emulsion. In the absence of
      CETP, the quantum yields of the fluorescent lipids is low because their high
      concentrations in the donor emulsions result in self-quenching. CETP catalyzes
      the redistribution of the fluorescent lipids from the donor to the acceptor
      emulsions and fluorescence increases substantially. Efficient sonication and
      incorporation of apolipoproteins from human HDL into the emulsions significantly
      increased the transfer rates. Under optimal conditions, the redistribution of
      fluorescent compounds reaches equilibrium within < 30 min and the kinetics of
      this process are consistent with a simple, first-order reaction pathway. The
      redistribution kinetics support a mechanism of adsorption --> exchange -->
      desorption --> diffusion.

PMID- 7586094
TI  - Solubilizing effects caused by alkyl pyridinium surfactants in
      phosphatidylcholine liposomes.
AB  - The solubilization of neutral and electrically charged liposomes by a series of
      alkyl pyridinium surfactants (alkyl chain lengths C10-C14) was investigated.
      Solubilization was detected as a decrease in static light-scattering of liposome
      suspensions. Two parameters were regarded as corresponding to the effective
      surfactant/lipid molar ratios at which the surfactant saturated the liposomes
      Re(sat) and led to a complete solubilization of these structures Re(sol). From
      these parameters the corresponding surfactant partition coefficients were
      determined. The Re and K parameters fell as the surfactant alkyl chain length
      decreased or both the critical micellar concentration (CMC) and the
      hydrophilic/lipophilic balance (HLB number) increased, regardless of the bilayers
      electrical charge. Thus, although decyl-pyridinium bromide (DePB) showed the
      highest ability for saturation and solubilization of bilayers, its concentration
      was always higher than that needed for dodecyl-pyridinium bromide (DoPB) and
      tetradecyl-pyridinium bromide (TePB), the last one being the most active. These
      results emphasize the influence of the hydrophilic/lipophilic balance of these
      surfactants on liposome solubilization and the minor influence of the
      electrostatic factors in this process.

PMID- 7586095
TI  - Interaction of undecaprenyl phosphate with phospholipid bilayers.
AB  - The effect of undecaprenyl phosphate (C55-P) on dioleoylphosphatidylcholine
      (DOPC) bilayer lipid membranes has been studied. The current-voltage
      characteristics, steady-state diffusion potentials, membrane conductance
      temperature relationships, membrane electric capacitance and membrane breakdown
      voltage have been measured for different mixtures of undecaprenyl phosphate and
      DOPC. The ratio of permeability coefficients for sodium and chloride ions, the
      activation energy for ion migration across the membrane and membrane thickness
      have been determined. The electrical measurements showed that undecaprenyl
      phosphate decreases membrane-normalized conductance, membrane ionic permeability,
      membrane hydrophobic thickness and membrane selectivity for chloride ions, and
      increases the activation energy for ion transport, membrane nonlinearity
      potential, membrane specific capacitance, membrane electromechanical stability
      and membrane selectivity for sodium ions. From the results, we suggest that the
      interaction of the gradient of electric transmembrane potential with the negative
      charge of the phosphate group of C55-P determines the dynamics, conformation and
      aggregation behaviour of undecaprenyl phosphate in phospholipid membranes. Some
      implications of these findings for a possible regulation of the C55-P-dependent
      expression of polysialic acid capsule in Escherichia coli K1 bacterial cells are
      indicated.

PMID- 7586093
TI  - Differential solubilization of lipids along with membrane proteins by different
      classes of detergents.
AB  - Membrane proteins are typically extracted by detergent concentrations of 0.5
      2.0%, using detergent/protein ratios of 1:1 to 3:1. We have compared the ability
      of 14 different detergents from seven different structural and ionic classes, at
      a concentration of 2.0% and a detergent/protein ratio of 2:1, to extract an
      integral membrane protein (the serotonin 5-HT1A receptor) in active form and have
      observed profound differences in both lipids and proteins. All extracts were
      freed from detergents and dialyzed to form vesicles containing 95-100% of the
      extracted lipids, prior to [3H]8-hydroxy-2-(N,N-di-n-propylamino)tetralin ([3H]8
      OH-DPAT) binding. The most efficient detergents in extracting active 5-HT1A
      receptor protein were the zwitterionic 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate (CHAPS) and 3-[(cholamidopropyl)dimethylammonio]-2-hydroxy-1
      propanesulfonate (CHAPSO), followed by the neutral n-dodecyl-beta-D-maltoside.
      Zwitterionic detergents also produced the highest solubilized lipid/protein ratio
      (3.0 and 2.5, respectively) and in general the relative amounts of extracted
      lipids and proteins followed inverse profiles. Thus, hydrophobic detergents such
      as Tritons (with critical micelle concentrations similar to CHAPS) and Thesit
      (structurally similar to Lubrol) extracted the most protein, but relatively
      little lipid (ratios of less than 0.2) and very little active 5-HT receptor.
      Dramatic differences were also observed in the ratios of individual lipids
      extracted by the same concentrations of different detergents and resolved by high
      performance thin-layer chromatography. For example, galactosylceramide (GalCer)
      content ranged from 2.7% (CHAPSO) to 13.4% (sodium cholate) of the total lipid
      extract and cholesterol ranged from 0% (digitonin) to 17.9% (Triton X-100). The
      detergent-extractability profile for phosphatidylethanolamine (PE) (range 15-40%
      of total lipid) paralleled that of phosphatidylinositol (PI) (range 4-10%), but
      was inverse to that for GalCer and cholesterol. Detergent-extractability profiles
      for phosphatidylcholine (PC) and phosphatidylserine (PS) also followed inverse
      profiles, with zwitterionic detergents giving high PS/PC and high PE/PC ratios
      (approximately 2:1), whereas the Tritons and digitonin gave ratios of 1:2. We
      believe that differential solubilization of lipids, as well as proteins, by
      detergents is important for the biological activity of the extracted proteins,
      and lipid extractability should be taken into account when purifying membrane
      proteins.

PMID- 7586096
TI  - Single crystal X-ray structures of the two 4-heptadecyl derivatives of (1R,5S)
      3,6,8-trioxabicyclo[3.2.1]octane.
AB  - The single crystal structures of the two diastereomeric 4-heptadecyl derivatives
      of (1R,5S)-3,6,8-trioxabicyclo[3.2.1]octane have been determined by X-ray
      diffraction to be (1R,4R,5S)-heptadecyl-3,6,8-trioxabicyclo[3.2.1]octane (I) and
      (1R,4S,5S)-4-heptadecyl[3,6,8-trioxabicyclo[3.2.1]octane (II), respectively,
      which have an exo or axial 4-heptadecyl group, and an endo or equatorial 4
      heptadecyl group, respectively. The structures of I and II had been suggested by
      their phase-sensitive 2D NOESY 1H-NMR spectra, but are now established
      unambiguously. These optically pure non-ionic lipid-like amphipathic molecules (I
      and II) represent the first 3,6,8-trioxabicyclo[3.2.1]octanes for which single
      crystal structures have been solved. Crystals of both isomer I and isomer II were
      orthorhombic with space group P2(1)2(1)2(1), and had unit cell dimensions of a =
      9.586, b = 43.14, c = 5.289 A, and a = 7.34, b = 51.8, c = 5.636 A, respectively.
      The structures of I and II were both solved by using direct methods to R = 0.045
      and R = 0.086, respectively. Both I and II pack in stacked bilayers with
      interdigitating and tilting hydrocarbon chains. The molecular and hydrocarbon
      cross sections are I: S = 50.70 A2, sigma = 19.00 A2; and II: S = 41.37 A2, sigma
      = 18.26 A2.

PMID- 7586097
TI  - Stereospecific labeling of the glycerol moiety: synthesis of 1,2-dioleoyl-sn-[3
      3H]glycero-3-phospho(1-rac-glycerol).
AB  - 1,2-Dioleoyl-sn-[3-3H]glycero-3-phospho(1-rac-glycerol) was synthesized from 1,2
      dioleoyl-sn-glycerol using a new radiosynthetic procedure. 1,2-Dioleoyl-sn
      glycerol was oxidized to the corresponding aldehyde using pyridinium dichromate
      and pyridine. The aldehyde was reduced to the radiolabeled alcohol using
      tritiated sodium borohydride and crown ether. This material was then converted to
      the phosphocholine derivative using 2-chloro-2-oxo-1,3,2-dioxaphospholane,
      followed by displacement with trimethylamine. In the last step, the 1,2-dioleoyl
      sn-[3-3H]glycero-3-phosphocholine was converted to 1,2-dioleoyl-sn-[3-3H]glycero
      3-phospho-(1-rac-glycerol) via a classic transphosphatidylation reaction using
      glycerol and cabbage phospholipase D. A theoretical explanation of unusual
      chemical behavior of the primary alcohol of diglycerides is also given, based on
      semi-empirical calculations.

PMID- 7586099
TI  - Fourier-transform infrared spectroscopic analysis of rabbit lung surfactant:
      subfraction-associated phospholipid and protein profiles.
AB  - Surfactant obtained from bronchoalveolar lavage (BAL) can be separated into
      subfractions based on sedimentation characteristics. It has been suggested that
      the 10,000 x g, 60,000 x g and 100,000 x g subfractions isolated by this approach
      represent stages of surfactant extracellular processing. These three subfractions
      have been reported to differ in their morphology, composition and ability to
      lower surface tension. We wished to determine if infrared spectroscopy, which may
      be applied as a non-invasive technique could potentially prove useful for
      characterization and quantification of bronchoalveolar lavage (BAL) protein and
      phospholipid, and if this approach could detect differences in intermediate
      surfactant processing stages. Subfractions were collected from adult rabbit lungs
      by BAL and differential centrifugation and analyzed by Fourier transform infrared
      (FT-IR) spectroscopy. Biochemical assay of phospholipid and protein showed
      differences between subfractions that correlated well with the
      phospholipid/protein ratios obtained from FT-IR spectra (r = 0.939; r2 = 0.882).
      The subfraction sedimenting at 100,000 x g (P100) exhibited spectral shifts in
      the Amide I band, suggesting that the protein secondary structure was different
      compared to other fractions. Spectra obtained after separation of lipids and
      protein components showed an apparent disordering of protein secondary structure
      but little or no effect on the structure or mobility of phospholipids. These
      results support the idea that subfractions represent various processing stages of
      surfactant. In addition, they show that results from FT-IR analyses correlate
      significantly with traditional biochemical assay methods which may prove of
      clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586098
TI  - An improved assay for measuring the transverse redistribution of fluorescent
      phospholipids in plasma membranes.
AB  - The internalization of fluorescent 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)
      phospholipids from the plasma membrane can be assessed by the irreversible
      quenching of analogues in the outer leaflet by dithionite. Here we have utilized
      this assay to follow the redistribution of short-chain C6-NBD-sphingomyelin and
      C6-NBD-phosphatidylserine from the cell membrane of human gingiva fibroblasts.
      The significant uptake of dithionite across the plasma membrane and the
      subsequent reduction of NBD-analogues exposed to the cytoplasmic lumen does not
      allow an accurate measurement of the amount of internalized lipid probes even at
      low temperature. We could show that a precise determination can be achieved by
      extraction of analogues remaining in the exoplasmic half by a short pretreatment
      with bovine serum albumin prior to addition of dithionite. The fluorescence of
      those analogues localized to the cytoplasmic lumen was slowly destroyed by
      permeating dithionite. The fluorescence of those NBD-probes which are localized
      in the inner layer of intracellular vesicles remained almost unaffected in the
      time course of the assay. Thus, this approach allows to distinguish between
      different routes of internalization of NBD-phospholipids from the plasma
      membrane.

PMID- 7586101
TI  - Spontaneous transfer of GM3 ganglioside between vesicles.
AB  - The spontaneous transfer between membranes of GM3, a ganglioside present in a
      vesicular form of aggregation instead of micellar form like the majority of
      gangliosides in aqueous medium, has been studied. Upon incubation of GM3 in the
      presence of dipalmitoylphosphatidylcholine (DPPC) large unilamellar vesicles at
      50 degrees C, mixed GM3/DPPC vesicles are formed. The maximum amount of GM3 that
      can be inserted into vesicles is about 8%. The temperature dependence of the
      kinetics has been followed by the excimer formation technique, using the
      fluorescent analogue pyrenyldodecanoyl-GM3. The transfer of ganglioside from its
      vesicles to DPPC vesicles depends on the physicochemical characteristics of both
      the donor and of the acceptor vesicles and increases with the temperature (k =
      0.006 0.012, 0.037 at 30, 41 and 50 degrees C, respectively), with a major break
      point at 41 degrees C and a minor one at 35 degrees C. These temperatures
      correspond to the gel- to liquid-crystalline transition of DPPC (Tm = 41.3
      degrees C), and to a temperature transition displayed by GM3 ganglioside. Similar
      experiments performed with erythrocyte ghosts yielded a rate constant of 0.04 at
      37 degrees C. For the transfer of ganglioside from DPPC (donor) to DMPC
      (acceptor) the rate constants were 0 at 15 degrees C (both phospholipids in the
      gel phase), 0.005 at 37 degrees C (donor in the gel phase, acceptor in the fluid
      phase) and 0.04 at 50 degrees C (both phospholipids in the fluid phase).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7586100
TI  - Changes induced in bovine serum albumin following interactions with the lipid
      peroxidation product E-2-octenal.
AB  - Bovine serum albumin (BSA) undergoes a number of deteriorative changes when
      exposed to E-2-octenal. Reaction of BSA with E-2-octenal produced fluorescent BSA
      with an excitation maximum at 350 nm and emission maximum at 440 nm and promoted
      polymerization. Amino acid analysis of the modified BSA showed that the E-2
      octenal treatment leads to the selective loss of lysine residues and the
      formation of new amino acid derivatives. The same products were detected in acid
      hydrolysates of poly-L-lysine and N2-(carbobenzyloxy)-L-lysine after their
      reactions with E-2-octenal. The reaction of N2-(carbobenzyloxy)-L-lysine with E-2
      octenal led to the production of 1-[N2-(carbobenzyloxy)-L-lysyl]-2- (1'
      carboxymethyl)-4-pentylpyridinium betaine, 1-[N2-(carbobenzyloxy)-L-lysyl]-2- (3'
      carboxy-2'-E-propen-1'-yl)-4- pentylpyridinium betaine and bis[1-[N2
      (carbobenzyloxy)-L-lysyl]-2- (3'-carboxy-2'-propen-1',2'-diyl)- 4
      pentylpyridinium betaine] (isomeric mixture). Upon acid hydrolysis, these
      quaternary pyridinium salts led to new amino acid derivatives, presumably 1-(L
      lysyl)-2-(1'-carboxymethyl)-4-pentylpyridinium betaine, 1-(L-lysyl)-2-(3'-carboxy
      2'-E-propen-1'-yl)- 4-pentylpyridinium betaine and bis[1-(L-lysyl)-2-(3'-carboxy
      2'-propen-1',2'-diyl)- 4-pentylpyridinium betaine] (isomeric mixture) that were
      indistinguishable from those obtained from BSA, poly-L-lysine and N2
      (carbobenzyloxy)-L-lysine after similar treatment. The reaction of lysine
      residues with E-2-octenal provides the basis for methods by which the
      contributions of E-2-octenal in the modifications of proteins can be determined.

PMID- 7586102
TI  - Hypothermic cardiopulmonary bypass--time for a more temperate approach.

PMID- 7586103
TI  - The management of temperature during hypothermic cardiopulmonary bypass: I-
      Canadian survey.
AB  - During hypothermic cardiopulmonary bypass (CPB) patients are cooled, usually to
      between 30-32 degrees C, and, after myocardial blood flow is restored, they are
      rewarmed with blood heated in the pump-oxygenator. We audited our local practice
      by recording tympanic and nasopharyngeal temperatures in 11 patients undergoing
      hypothermic CPB. We found that, during rewarming, nasopharyngeal and tympanic
      temperatures commonly exceeded 38 degrees C although temperature measured in the
      bladder was < 37 degrees C. A survey of cardiac surgery centres in Canada
      suggested that most centres induce hyperthermia in highly perfused tissues during
      rewarming, sometimes inadvertently. This may be of some importance because it has
      become widely appreciated by neuroscientists that mild degrees of brain cooling
      (2-5 degrees C) are capable of conferring dramatic protection from ischaemic
      brain injury and, conversely, mild temperature elevation may be markedly
      deleterious. If control of brain temperature is considered desirable then we
      would suggest that nasopharyngeal temperature be monitored during rewarming on
      CPB.

PMID- 7586104
TI  - The management of temperature during hypothermic cardiopulmonary bypass: II-
      Effect of prolonged hypothermia.
AB  - In animals mild hypothermia (32-35 degrees C) reduces ischaemic brain injury, but
      this has not been investigated in humans. During hypothermic cardiopulmonary
      bypass (CPB) patients are made hypothermic (usually to 30-32 degrees C) but are
      then rewarmed at a time when they are still at risk of ischaemic brain injury. We
      investigated the feasibility and safety of maintaining mild hypothermia
      throughout the CPB period. Thirty adult cardiac surgical patients were randomized
      to either rewarming to 36-37 degrees C or to maintaining temperature at 34
      degrees C without rewarming. On arrival in the recovery room, patients in the
      hypothermic group had a mean bladder temperature of 33.8 +/- 0.45 degrees C
      compared with 35.4 +/- 0.58 degrees C (mean +/- SD, P < 0.05) in the rewarmed
      patients. There were no differences between groups in intra- or postoperative
      blood loss or blood use, inotrope use, dysrhythmias, or myocardial infarction.
      The hypothermic group received more muscle relaxant for the treatment of
      shivering postoperatively. Our results suggest that mild hypothermia following
      CPB did not increase morbidity although larger studies are needed for
      confirmation.

PMID- 7586105
TI  - Sedative and ventilatory effects of midazolam infusion: effect of flumazenil
      reversal.
AB  - The purpose of this study was to evaluate the effects of flumazenil (1 mg i.v.)
      on the ventilatory response of premedicated patients receiving a continuous
      infusion of midazolam for sedation. After assessing baseline ventilatory function
      using a modified Read rebreathing method for determining hypercapnic ventilatory
      drive, 16 healthy outpatients were administered fentanyl, 50 micrograms i.v., and
      midazolam 2 mg i.v., followed by a variable-rate midazolam infusion, 0.3-0.5
      mg.min-1. Upon termination of the midazolam infusion, serum midazolam
      concentrations were measured and ventilatory function was reassessed. Then, 10 ml
      either saline or flumazenil (1 mg) were administered according to a randomized,
      double-blind protocol. Ventilatory function was subsequently measured at 5 min,
      30 min and 60 min intervals after study drug. Compared with the baseline value,
      midazolam infusion reduced tidal volume and increased respiratory rate and
      alveolar dead space. However, midazolam did not decrease the slope of the CO2
      response curve. Flumazenil reduced the degree of midazolam-induced sedation and
      the decrease in tidal volume (P < 0.05), but not the change in resting
      respiratory rate. In some patients, the ventilatory response to hypercarbia
      actually decreased after flumazenil administration compared with the immediate
      prereversal (sedated) values. It is concluded that midazolam infusion, 0.43
      mg.min-1, did not impair CO2-responsiveness. Flumazenil's effect on central
      ventilatory drive was more variable than its reversal of midazolam-induced
      sedation.

PMID- 7586106
TI  - Upper airway obstruction during midazolam sedation: modification by nasal CPAP.
AB  - We examined the depressant effect of midazolam on respiration in 21 healthy women
      undergoing lower abdominal surgery with spinal anaesthesia. Airway gas flow,
      airway pressure, and the sound of snoring were recorded together with arterial
      oxygen saturation (SpO2). After spinal anaesthesia was established, subjects were
      deeply sedated with pentazocine 15 mg followed by incremental doses of midazolam
      1 mg i.v. up to 0.1 mg.kg-1. When SpO2 decreased to < 90% or snoring and/or
      apnoea was observed, continuous positive airway pressure applied through the nose
      (nasal CPAP) was increased until the respiratory deterioration was reversed.
      While one patient remained free of respiratory events, the other 20 patients were
      successfully treated with nasal CPAP restoring normal SpO2 (95.5 +/- 1.7%)
      without snoring. Stepwise reduction of nasal CPAP determined the minimally
      effective CPAP to prevent snoring to be 5.1 +/- 2.1 cm H2O. Further reduction of
      nasal CPAP induced snoring in 15 patients and obstructive apnoea in five patients
      with the latter accompanied by a severe reduction of SpO2 (87.4 +/- 6.1%).
      Patients with apnoea were older than those who snored (P < 0.05. We conclude that
      upper airway obstruction contributes considerably to decreases in SpO2 during
      midazolam sedation for spinal anaesthesia.

PMID- 7586108
TI  - Left ventricular regional wall motion and haemodynamic changes following bolus
      administration of pipecuronium or pancuronium to adult patients undergoing
      coronary artery bypass grafting.
AB  - The objective of this study was to compare the haemodynamic and myocardial
      effects of pipecuronium and pancuronium in patients undergoing coronary artery
      bypass grafting (CABG) during benzodiazepine/sufentanil anaesthesia. Twenty-seven
      ASA III-IV patients received lorazepam (1-3 mg) po and midazolam ( < 0.1 mg.kg-1)
      i.v. before induction of anaesthesia with sufentanil (3-8 micrograms.kg-1) was
      administered to facilitate tracheal intubation. According to random allocation,
      each patient received either pipecuronium (150 micrograms.kg-1) or pancuronium
      (120 micrograms.kg-1) after sternotomy but before heparinization. Mean arterial
      pressure, central venous pressure (CVP), pulmonary artery pressure (PAP), ST
      segment position and ECG (leads III, V5, AVF) were monitored continuously
      throughout the procedure. Thermodilution determinations of CO in triplicate were
      made immediately before, and at two and five minutes after muscle relaxant
      administration. Multiplane transoesophageal echocardiography (TEE, midpapillary
      short axis views of the left ventricle) images were continuously recorded from
      ten minutes before until ten minutes after muscle relaxant administration and
      graded by two experienced echocardiographic readers. Heart rate, MAP and CO
      increased after administration of pancuronium (by 13.6 beats.min-1, 10.8 mmHg and
      1.0 L.min-1 respectively) but not after pipecuronium (P < 0.05). Evidence of
      myocardial ischaemia was not detected in any patients using ECG ST segment
      analysis or TEE assessment of left ventricular wall motion. We conclude that
      pancuronium caused increases in HR, MAP and CO but that neither pancuronium nor
      pipecuronium caused myocardial ischaemia.

PMID- 7586107
TI  - Hypobaric spinal anaesthesia with bupivacaine (0.1%) gives selective sensory
      block for ano-rectal surgery.
AB  - Twenty adult male patients undergoing anorectal surgery in the jackknife position
      under spinal anaesthesia were studied for the anaesthetic properties of 5 ml
      hypobaric 0.1% bupivacaine. The patients were positioned in the prone, jack-knife
      position with a pillow under the hips and with an operating table break
      angulation of 30 degrees with head down tilt of 20 degrees. In this position a 25
      gauge Quincke spinal needle was inserted intrathecally through L3-4 and 5 ml
      solution, prepared by mixing 1 ml bupivacaine 0.5% with 4 ml of distilled water
      with a specific gravity of 1.001 at 20 degrees C, was given over 15-20 sec. Onset
      time, progression and upper level of sensory blockade evaluated by pin prick, and
      the extent of motor block (1 = full motor movement at ankle and knee joint, 2 =
      restricted motor movements, 3 = full motor block, no movements) were measured at
      one minute intervals for the first five minutes, then every five minutes for 30
      min. The number of dermatomes blocked was also noted. The median level of
      cephalad sensory blockage was of L1, with a range from T10-L3. On average, nine
      dermatomes were blocked (range 7-12). Motor blockade was not observed in any
      patient. Changes in heart rate and blood pressure were minimal. The average
      duration of postoperative analgesia was 339.5 +/- 182.9 min. Post-spinal headache
      was not observed in any patients. In conclusion, 5 ml intrathecal hypobaric
      bupivacaine, 0.1%, provided excellent perioperative analgesia without motor
      blockade and haemodynamic stability in patients undergoing anorectal surgery in
      jackknife position.

PMID- 7586110
TI  - Comparison of 26-gauge Atraucan and 25-gauge Whitacre needles: insertion
      characteristics and complications.
AB  - Ninety-six women undergoing post-partum tubal ligation under spinal anaesthesia
      were studied to compare 26G Atraucan with 25G Whitacre spinal needles for ease of
      insertion, number of attempts at needle insertion, cerebrospinal fluid (CSF) flow
      characteristics through the needles, quality of subsequent analgesia, and
      incidence of perioperative complications. A higher rate of successful dural
      puncture at the first attempt (40/50 vs 27/46, P < 0.05) and faster (mean +/- SD,
      11.5 +/- 2.2 vs 13.5 +/- 2.4, P < 0.001) CSF flow through the needle was achieved
      with the Atraucan than with the Whitacre needle. The incidence of failed spinal
      (4% vs 5%) and post-dural puncture headache (PDPH) (4% vs 4.3%) was similar with
      both needles, but more patients experienced paraesthesiae during needle insertion
      with the Whitacre than with the Atraucan needle (15% vs 2%, P < 0.05). We
      conclude that the use of the 26G Atraucan needle is associated with a higher rate
      of successful identification of the subarachnoid space at the first attempt,
      faster CSF backflow, and fewer paraesthesia when compared with the 25G Whitacre
      needle.

PMID- 7586111
TI  - Perioperative train-of-four monitoring and residual curarization.
AB  - It has been suggested that perioperative train-of-four (TOF) monitoring does not
      reduce the incidence of postoperative residual curarization (PORC). The purpose
      of this study was to examine whether the use of tactile assessment of the
      response of the adductor pollicis to supramaximal TOF stimulation of the ulnar
      nerve at the wrist during anaesthesia affected the incidence of PORC. Thirty-nine
      ASA I or II surgical patients were studied during thiopentone/fentanyl
      N2O/enflurane anaesthesia. Pancuronium (70-100 micrograms.kg-1) was used to
      facilitate tracheal intubation and additional pancuronium increments used to
      maintain surgical relaxation. The requirement for incremental doses of
      pancuronium and adequacy of recovery following reversal were assessed according
      to random allocation, either with (Group A; n = 20) or without (Group B; n = 19)
      access to TOF monitoring. Patients in the two groups received neostigmine in
      similar doses (Group A: 53 micrograms.kg-1 (5.9); Group B: 55 micrograms.kg-1
      (5.4)). On arrival of the patient to the recovery area, neuromuscular function
      was assessed electromyographically (using the Datex NMT 221 to measure TOF ratio)
      and clinically. The incidence of PORC (TOF ratio < 70%) was greater in Group B
      (47%) than in Group A (15%) (P = 0.029). We conclude that the use of
      perioperative TOF monitoring decreases the incidence of pancuronium-induced PORC.

PMID- 7586112
TI  - High-dose vecuronium neuromuscular block: a comparison of arrhythmias and onset
      of block during sufentanil anaesthesia.
AB  - This study compared the heamodynamic effects of sufentanil with those observed
      following concomitant sufentanil and high-dose vecuronium administration to
      determine whether vecuronium induces bradyarrhythmias. Sixty coronary artery
      bypass patients were stratified into beta blocker (n = 30) or non-beta blocker (n
      = 30) groups and following induction with sufentanil (9 +/- 3 micrograms.kg-1)
      and midazolam (0.07 +/- 0.04 mg.kg-1), received either succinylcholine 1 mg.kg-1
      (SxCh), vecuronium 0.3 mg.kg-1 (Vec 0.3), or vecuronium 0.5 mg.kg-1 (Vec 0.5).
      Using a Holter ECG monitor, bradyarrhythmias were classified as mild (HR 46-50),
      moderate (HR 40-45) or severe (HR < 40). In the pre-induction period, there were
      no differences in the incidence of mild, moderate or severe bradyarrhythmias
      among the SxCh, Vec 0.3 or Vec 0.5 groups, in either the beta blocker or non-beta
      blocker groups. Following induction, there were similar reductions in mean heart
      rate and mean arterial pressure in all three muscle relaxant groups in both the
      beta and the non-beta blocker groups; however, there was no difference in the
      incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or
      Vec 0.5 groups. The Vec 0.5 beta blocker group had a higher incidence of mild
      bradyarrhythmias (32 +/- 36%) than the Vec 0.5 non-beta blocker group (2 +/- 3%,
      P = 0.017). Using EMG recording, the onset time of maximal neuromuscular block
      for the Vec 0.3 group (108 +/- 17 sec) was longer (P < 0.05) than the SxCh (76 +/
      21 sec) and Vec 0.5 (82 +/- 13 sec) groups, which were similar.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7586109
TI  - A directional needle improves effectiveness and reduces complications of
      microcatheter continuous spinal anaesthesia.
AB  - The present prospective randomized study compares the impact of two different
      spinal needle designs--non-directional versus directional--on the effectiveness
      of continuous spinal anaesthesia provided via a microcatheter in orthopaedic
      patients. Using the midline approach, a 28-gauge spinal catheter was inserted
      either through a 22-gauge Quincke needle (non-directional, Group 1, n = 21) or a
      22-gauge Sprotte needle (directional, Group 2, n = 21) under standardized
      conditions. The incidence of technical difficulties and postoperative complaints,
      onset time of analgesia at the level of T10 and dose requirement of plain
      bupivacaine 0.5% were recorded. Postoperatively, the subarachnoid position of the
      catheters was radiographically evaluated. There was a higher incidence of
      technical problems during catheter insertion in Group 1 compared with Group 2
      (71% vs 19%, P < 0.05). Onset time of analgesia was shorter (P < 0.05) and
      anaesthetic dose requirement was lower in patients in Group 2 than in Group 1.
      While 40% of the catheters were found in a caudal position in Group 1, all
      catheters were in a cranial position or at the level of the puncture site in
      Group 2 (P < 0.05). There was no difference in the incidence of postoperative
      complaints between the groups. The faster onset of analgesia and lower dose
      requirement of local anaesthetics associated with a lower incidence of technical
      problems suggest that there is greater effectiveness and safety when
      microcatheters are inserted using directional needles rather than non-directional
      needles.

PMID- 7586113
TI  - Should the routine use of atropine before succinylcholine in children be
      reconsidered?
AB  - It is common practice to administer atropine before a first dose of
      succinylcholine in infants and children. However, the administration of
      succinylcholine without atropine has not been investigated in children. This
      study was designed to compare cardiovascular changes after the administration of
      either atropine with succinylcholine or succinylcholine alone. In 41 ASA I or II
      patients aged from 1 to 12 yr anaesthesia was induced with thiopentone 5 mg.kg-1.
      Patients were randomly allocated to receive either atropine 20 micrograms.kg-1
      and succinylcholine 1.5 mg.kg-1 (n = 20) or succinylcholine 1.5 mg.kg-1 alone (n
      = 21). Heart rate and rhythm were recorded continuously from two minutes before
      induction until two minutes after tracheal intubation. Blood pressure was
      measured non-invasively before and after induction of anaesthesia and both
      immediately and two minutes after laryngoscopy. One self-limiting episode of
      bradycardia was recorded during laryngoscopy in a child who received atropine.
      Heart rate increased in both groups compared with baseline values (108 +/- 25),
      with a greater increase in patients who had received atropine (150 +/- 13) than
      in those who had not (128 +/- 18) (P < 0.05). There was no difference in mean
      arterial pressure or incidence of arrythmias between the two groups. No recorded
      arrythmias were judged to be clinically important by a cardiologist. The
      incidence of bradycardia after succinylcholine in the absence of atropine in
      children aged from 1 to 12 yr appears to be lower than previously estimated. The
      use of atropine before a single dose of succinylcholine in children deserves to
      be reconsidered.

PMID- 7586114
TI  - Gastric fluid volume and pH after nizatidine in adults undergoing elective
      surgery: influence of timing and dose.
AB  - We conducted a prospective, randomized, double-blind study to investigate the
      effect of oral nizatidine (150-600 mg), a new potent H2 antagonist, on
      preoperative gastric fluid pH and volume in adults undergoing elective surgery.
      One hundred and seventy-five healthy adults (21-68 yr) were randomly allocated to
      seven treatment groups (n = 25); Placebo was administered at 21:00 and 06:30 the
      night before and on the day of surgery, respectively (0/0: control); nizatidine
      150 mg at 21:00 and placebo at 06:30 (150/0); placebo at 21:00 and nizatidine 150
      mg at 06:30 (0/150); nizatidine 150 mg at 21:00 and 06:30 (150/150); nizatidine
      300 mg at 21:00 and placebo at 06:30 (300/0); placebo at 21:00 and nizatidine 300
      mg at 06:30 (0/300); and nizatidine 300 mg at 21:00 and 06:30 (300/300). Each
      patient fasted overnight and took the drug and/or placebo with 20 ml water. After
      induction of anaesthesia, the pH and volume of gastric fluid obtained through an
      orogastric tube were measured. The mean pH of 0/150, 150/150, 300/0, 0/300, and
      300/300 groups was higher than that of the control group (P < 0.05). Gastric
      volume in these groups was smaller than in the control (P < 0.05). The 150/0
      group failed to decrease gastric fluid volume and increase pH. In the 300/0
      group, the gastric pH was lower than other regimens which effectively decreased
      gastric acidity (P < 0.05). The number of patients with a pH < 2.5 and a volume >
      0.4 ml.kg-1 in the 0/150, 150/150, 0/300, and 300/300 groups (0%) was less than
      in the control group (16%) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586116
TI  - Sudden unexpected sneezing during the insertion of peribulbar block under
      propofol sedation.
AB  - The author presents a case report where, following propofol sedation for a
      peribulbar block, sneezing was induced once the local anaesthetic needle was
      placed in the orbital cavity. The physiology of sneezing is discussed, as well as
      the pathophysiology of the ACHOO (Autosomal Dominant Compelling Helio-Ophthalmic
      Outburst) syndrome, an autosomal dominant condition, present in approximately 25%
      of the population, where sneezing is provoked upon exposure to bright light. It
      is suggested that the anaesthesia induced by propofol may have sensitized
      patients with this condition to sneeze, since there appeared to be no other
      excitatory sequelae which have previously been described with propofol.

PMID- 7586115
TI  - Twelve hour anaesthesia in a patient with epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB), an inherited disorder presents clinically with
      recurrent cutaneous blister formation with possible involvement of mucous
      membranes and other organs. The sequelae of this disease pose multiple challenges
      to the anaesthetist and operating room team. Recent literature describes several
      anaesthetic techniques for the short surgical procedures this patient population
      may undergo. We describe the anaesthetic technique employed in a 28-yr-old women
      with recessive dystrophic epidermolysis bullosa who underwent 12 hr
      reconstructive surgery followed by a review of the literature that includes a
      recent description of the possible association of EB with at least two distinct
      neuromuscular diseases. A detailed description of airway and skin management is
      described in addition to preoperative concerns. We conclude that a prolonged
      operative procedure can be undertaken successfully in this population with
      minimal sequelae involving skin integrity and airway management.

PMID- 7586117
TI  - Prolonged myoclonus and meningism following propofol.
AB  - The purpose of this report is to describe a new complication of propofol
      administration. A previously fit patient underwent intravenous anaesthesia with
      propofol for removal of dental wires. Postoperatively he developed myoclonic
      jerking of his limbs. On regaining consciousness he complained of an occipital
      headache, neck stiffness and photophobia, and was found to have nuchal rigidity
      on examination. These clinical features resolved over the following week.
      Subsequent investigations failed to explain the aetiology of the symptoms of
      meningeal irritation, which suggests that propofol was the causative agent. While
      prolonged myoclonus has been previously described with propofol administration,
      this is the first report of meningism occurring with its use.

PMID- 7586118
TI  - Ultrathin fibreoptic laryngoscope.

PMID- 7586119
TI  - Attenuation of the pressor response to laryngoscopy--misquotation.

PMID- 7586120
TI  - Laryngoscopy and arrhythmias in children.

PMID- 7586121
TI  - Authorship in anaesthesia journals.

PMID- 7586122
TI  - LMA in neurosurgery.

PMID- 7586123
TI  - Vitamin C as placebo.

PMID- 7586126
TI  - Topoisomerase inhibition by phenolic metabolites: a potential mechanism for
      benzene's clastogenic effects.
AB  - Exposure to benzene, a human and animal carcinogen, results in the formation of
      structural chromosomal aberrations in the bone marrow and blood cells of animals
      and humans. The mechanisms underlying these clastogenic effects are unknown.
      Inhibition of enzymes involved in DNA replication and repair, such as
      topoisomerase enzymes, by the metabolites of benzene represents a potential
      mechanism for the formation of chromosomal aberrations. To test this hypothesis,
      the inhibitory effects of various phenolic and quinone metabolites of benzene on
      the activity of human topoisomerases I and II were studied in vitro. No
      inhibition of topoisomerase I was seen with any of the tested metabolites.
      Inhibitory effects on topoisomerase II were not observed for hydroquinone,
      phenol, 2,2'-biphenol, 4,4'-biphenol and catechol at concentrations as high as
      500 microM. 1,4-Benzoquinone and 1,2,4-benzenetriol inhibited topoisomerase II at
      relatively high 500 and 250 microM concentrations, respectively. However
      following bioactivation using a peroxidase/H2O2 system, inhibitory effects were
      seen at concentrations as low as 50 microM for both phenol and 2,2'-biphenol and
      10 microM for 4,4'-biphenol. The addition of reduced glutathione (GSH) to the
      4,4'-biphenol and horseradish peroxidase reaction system protected topoisomerase
      II from inhibition suggesting that diphenoquinone or another oxidation product
      formed from 4,4'-biphenol might be the reactive species. These in vitro results
      indicate that inhibition of topoisomerase II may contribute to the clastogenic
      and carcinogenic effects of benzene. In addition, metabolites formed from these
      phenolic compounds appear to represent several new types of topoisomerase II
      inhibiting compounds.

PMID- 7586125
TI  - Induction of p53 in mouse cells decreases mutagenesis by UV radiation.
AB  - The tumor suppressor protein, p53, is proposed to have a critical role in
      maintaining the integrity of the genetic material. It has been established that
      p53 induces a cell cycle block in the G1 phase upon cellular DNA damage. Recent
      evidence also indicates the involvement of p53 directly and indirectly in
      nucleotide excision repair (NER). We have examined the role of p53 with respect
      to UV-induced mutagenesis. By gene transfer, we established a mouse fibroblast
      cell line overexpressing the val135 temperature-sensitive p53 allele. In this
      line, p53 activity can be modulated through temperature shift, as confirmed by
      Western blot and by cell cycle analysis. This cell line was also constructed to
      contain a recoverable lambda phage shuttle vector carrying the supF mutation
      reporter gene. Induction of p53 was found to enhance the clonogenic survival of
      the cells following UV-irradiation compared to the p53-deficient parental mouse
      cell line. The transfectant line also displayed a 4-fold reduction in the
      frequency of UV-induced mutations as measured in the chromosomally integrated
      supF reporter gene. Our results are consistent with a p53-induced cell cycle
      block at G1 allowing cells to repair chromosomal damage before DNA replication.
      However, our data may also reflect a more direct role of p53 in the repair of UV
      induced lesions as suggested by studies showing that p53 can interact directly
      with repair factors.

PMID- 7586127
TI  - In vitro mutagenicity studies on cyproterone acetate using female rat hepatocytes
      for metabolic activation and as indicator cells.
AB  - The synthetic sex steroid cyproterone acetate (CPA) was shown to induce DNA
      repair in primary hepatocytes from female rats, confirming previous reports about
      a sex-specific genotoxic potential of CPA in female rat liver. CPA did not induce
      gene mutations or chromosomal aberrations in V79 Chinese hamster cells co
      cultivated with hepatocytes from female rats as the metabolizing system.
      Hepatocytes from the same rats under identical exposure conditions as in the
      positive unscheduled DNA synthesis (UDS) test were used in these experiments. The
      maximum concentrations tested in the mutagenicity assays were 30-100 times higher
      compared with the lowest observed effect concentration of 3 x 10(-6) mol/l in the
      DNA repair test. The requirement for cell-cell transfer of the putative genotoxic
      metabolites in the co-culture experiments may be the reason for the discrepancy
      between positive UDS effects and negative mutagenicity and clastogenicity
      results. To further investigate if CPA can induce chromosomal mutations within
      the same cells that provide metabolic activation an in vitro micronucleus assay
      with proliferating female rat hepatocytes was performed. The results gave some
      indications of a micronucleus-inducing potential of CPA. However, under the
      conditions of the micronucleus assay CPA was also shown to increase the
      proliferative activity of hepatocytes. Since micronucleus formation is also
      dependent on mitotic activity, it cannot be determined whether the increase in
      micronucleus formation after CPA exposure indicates a clastogenic potential or
      whether it is just a consequence of the mitogenic potential of CPA. Although CPA
      or its metabolites obviously have a DNA damaging potential and stimulate
      considerable DNA excision repair, our findings do not establish a clear mutagenic
      potential.

PMID- 7586128
TI  - Genotoxicity of zearalenone, an estrogenic mycotoxin: DNA adduct formation in
      female mouse tissues.
AB  - Zearalenone is a non-steroidal estrogenic mycotoxin produced by several species
      of Fusarium which colonize maize, barley, oats, wheat and sorghum and have been
      implicated in numerous mycotoxicoses in farm animals, especially pigs. In a NTP
      mouse study a dose-related incidence of hepatocellular adenomas was seen in
      female mice. A limited number of genotoxicity assays have been conducted with
      zearalenone. Zearalenone was found to be negative in the Salmonella typhimurium
      assay. It was also negative in a eukaryotic cell mutation assay with
      Saccharomyces cerevisae. However, zearalenone and its estrogenic metabolites
      showed a positive DNA damaging effect in recombination tests with Bacillus
      subtilis. In this study DNA adducts in female mice and rat treated i.p or orally
      with zearalenone were determined using a 32P-postlabeling method. Several DNA
      adducts (12-15) were found in the kidney and liver of female mice treated with a
      single dose of zearalenone (2 mg/kg i.p. or orally). The total DNA adduct levels
      reached 114 +/- 37 and 1393 +/- 324 adducts/10(9) nucleotides respectively in
      kidney and liver after i.p. treatment and 548 +/- 50 adducts/10(9) nucleotides in
      liver after oral treatment. In mice ovary DNA adducts appeared only after
      repeated doses (1 mg/kg body wt on days 1, 5, 7, 9 and 10). The total DNA adducts
      after 10 days in this organ were 17 +/- 5 adducts/10(9) nucleotides. Some adducts
      were common to all organs. Others were specific to an organ. In contrast, no DNA
      adducts could be detected in rat organs after i.p. treatment. These results
      confirm the genotoxicity of zearalenone and its ability to induce hepatocellular
      adenomas, rather than tumours of genital organs, in mice.

PMID- 7586129
TI  - Inhibition of gap junctional intercellular communication by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in rat hepatocytes.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent rodent hepatic tumor
      promoter. Unlike observations with the majority of tumor promoting chemicals
      studied to date, most investigations have failed to demonstrate down-regulation
      of gap junctional intercellular communication (GJIC) in cultured cells by TCDD.
      The present study examined the effect of TCDD on GJIC in rat hepatocytes in
      primary culture. At non-cytolethal doses TCDD inhibited GJIC in a time- (1, 4, 24
      and 48 h) and concentration (1 x 10(-8) - 1 x 10(-14) M)-dependent manner. This
      inhibition occurred within 4 h of treatment at doses of 1 x 10(-8) - 1 x 10(-12)
      M TCDD and persisted for up to 48 h, despite removal of TCDD. Treatment of rat
      hepatocytes with TCDD resulted in a decrease in hepatocyte connexin 32 mRNA, but
      had no apparent effect on connexin 26 mRNA. Co-incubation of rat hepatocytes with
      TCDD and alpha-napthoflavone abolished down-regulation of GJIC by TCDD.
      Similarly, co-treatment with a cAMP analog (8-bromoadenosine 3',5'-cyclic
      monophosphate) prevented down-regulation of GJIC by TCDD. The results of this
      investigation demonstrated, for the first time, that TCDD inhibits GJIC in the in
      vivo target of its tumor promoting effect and that this effect may, in part, be
      mediated through the Ah receptor. In addition, this study showed that inhibition
      of GJIC by TCDD may be due to transcriptional down-regulation or stability of the
      connexin 32 gap junction mRNA.

PMID- 7586124
TI  - Oxidation of 1,2-epoxy-3-butene to 1,2:3,4-diepoxybutane by cDNA-expressed human
      cytochromes P450 2E1 and 3A4 and human, mouse and rat liver microsomes.
AB  - 1,3-Butadiene is carcinogenic in B6C3F1 mice and Sprague-Dawley rats, and has
      been classified as a probable human carcinogen. The genetic basis for butadiene
      carcinogenicity is likely mediated by its metabolite, 1,2:3,4-diepoxybutane
      (BDE). Oxidation of butadiene to 1,2-epoxy-3-butene (BMO) and further activation
      to BDE is catalysed by cytochrome P450 (CYP) isozymes. The production of BMO from
      butadiene is mediated by CYP2E1 and, at high butadiene concentrations, by CYP2A6.
      The purpose of the present study was to identify which human CYP isozymes have
      the ability to oxidize BMO to BDE, and to determine the extent to which this
      reaction occurs in B6C3F1 mouse, Sprague-Dawley rat, and human liver microsomes.
      Of the human cDNA-expressed CYP isozymes tested, only CYP2E1 formed detectable
      concentrations of BDE at 80 microM BMO. CYP2E1 and CYP3A4 were active at 5.0 mM
      BMO. Interindividual and interspecies variation in the initial rate of oxidation
      of 80 microM BMO to BDE was determined using 10 samples of human liver microsomes
      and single pooled samples from rats and mice. Those experiments revealed a 60
      fold variation in activity among 10 human liver samples (range: 0.005-0.324
      nmol/mg protein/min). Rates of BMO oxidation for mouse and rat liver microsomes
      were 0.473 and 0.166 nmol/mg protein/min, respectively. Apparent kinetic
      constants for the oxidation of BMO to BDE by four human microsomal preparations,
      and pooled samples from mice and rats were estimated from detailed investigations
      of BMO oxidation at various BMO substrate concentrations. Apparent Km for the
      human liver samples ranged from 0.304-0.880 mM, and Vmax values ranged from 0.38
      to 1.2 nmol/mg protein/min. The apparent values of Km and Vmax for mouse liver
      microsomes were 0.141 +/- 0.007 mM (mean +/- SE) and 1.303 +/- 0.141 nmol/mg
      protein/min, respectively. For rat liver microsomes, apparent Km and Vmax were
      0.145 +/- 0.036 mM and 0.408 +/- 0.031 nmol/mg protein/min, respectively.
      Measured rates of BDE formation correlated well with CYP2E1 protein
      concentrations in the human microsome samples. These results implicate human
      CYP2E1 as a hepatic isoform responsible for the oxidation of BMO to BDE at low
      concentrations of BMO. Moreover, our in vitro results reveal that microsomes
      prepared from human, rat and mouse liver possess the ability to form BDE from
      BMO. Previous in vitro results suggest that following exposure to butadiene more
      BMO would probably be present in mice than in rats or humans. Thus, in mice more
      BMO would be available for activation to BDE.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7586130
TI  - The expression of placental-type glutathione S-transferase (GST-pi) in human
      cutaneous carcinoma in situ, that is, actinic keratosis and Bowen's disease,
      compared with normal human skin.
AB  - The expression of human placental type glutathione S-transferase (GST-pi) was
      investigated in human cutaneous carcinoma in situ, that is, actinic keratosis and
      Bowen's disease, and compared with that in normal skin, using Northern blot and
      immunohistochemical analysis. In Northern blot examination, the expression of GST
      pi transcript was recognized in all instances. Carcinoma in situ showed
      significantly higher expressions of GST-pi than normal skin. In the
      immunohistochemical examination, nuclear staining of GST-pi was noticed in some
      dysplastic cells of carcinoma in situ, especially in Bowen's disease. In actinic
      keratosis, a framework appearance was noticed in the staining pattern at a lower
      magnification because the lower part of the cytoplasm of dysplastic cells lining
      the stratum basale was positive for GST-pi, and all cells of the stratum
      granulosum and more cells of the stratum spinosum showed stronger GST-pi positive
      reaction than normal skin. In Bowen's disease, GST-pi positive, dysplastic cells
      existed throughout the epidermis. Because GST-pi positive, dysplastic cells and
      GST-pi positive, normal looking squamous cells made the GST-pi positive cell
      nests throughout the epidermis, and GST-pi positive, dysplastic cells, and GST-pi
      negative, normal looking cells coexisted in the parabasal layer, they showed a
      sawtooth appearance in the staining pattern at a lower magnification. These
      findings suggest that GST-pi is involved in the process of carcinogenesis.

PMID- 7586133
TI  - cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of
      spontaneous mutations due to oxidation of guanine nucleotides.
AB  - The enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase), is
      present in various organisms and plays an important role in control of
      spontaneous mutagenesis. This enzyme degrades 8-oxoguanine-containing
      deoxyribonucleoside triphosphate, a potentially mutagenic substrate for DNA
      synthesis, to the corresponding monophosphate. To obtain appropriate probes for
      expression of the gene in various tissues and also to construct appropriate
      experimental models for carcinogenesis, we cloned cDNA for rat 8-oxo-dGTPase and
      elucidated its structure. The nucleotide sequence of the cDNA revealed that the
      rat 8-oxo-dGTPase protein is composed of 156 amino acid residues. The molecular
      weight of rat 8-oxo-dGTPase, calculated from the predicted amino acid sequence,
      was 18,006, and the 8-oxo-dGTPase protein of this size was detected when the cDNA
      was expressed in 8-oxo-dGTPase-deficient Escherichia coli mutT- cells. The
      predicted amino acid sequence of the rat 8-oxo-dGTPase has a close homology with
      those of human and bacterial counterparts. Using the cDNA as a probe, part of the
      rat gene for 8-oxo-dGTPase was isolated and was found to consist of at least
      three exons and spanned about 10 kb. A genomic region containing the pseudogene
      was also isolated.

PMID- 7586131
TI  - Risk of smoking for squamous and small cell carcinomas of the lung modulated by
      combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population.
AB  - Genes for cytochrome P4501A1 (CYP1A1) and glutathione S-transferase class mu
      (GSTM1) have been shown to be polymorphic, and have been implicated in tobacco
      related carcinogenesis. In the present study, the role of the combined genotypes
      CYP1A1 and GSTM1 as a possible modulator of smoking related lung cancers was
      studied in relation to the tobacco smoke exposure level in 118 Japanese patients
      aged < 70 with squamous or small cell carcinomas of the lung. Among male smoking
      patients, the overall proportion of the GSTM1 null genotype (GSTM1[-]) was
      slightly higher than among healthy male smoker controls (56.7% versus 48.1%, P =
      0.17). Little difference was observed between smoker patients and corresponding
      controls in overall frequencies of m2 mutant allele homozygotes (CYP1A1[m2/m2])
      (16-18%) and Val encoding allele homozygotes (5-6%). However, when subjects were
      categorized by both CYP1A1 genotype (MspI polymorphism) and GSTM1 genotype,
      GSTM1(-) became markedly more expressed in patients with CYP1A1(m2/m2) when
      compared to the corresponding smoker controls (81.3% versus 39.4%, P < 0.01).
      When odds ratios were estimated using nonsmoking patients and healthy controls as
      a reference, the relative risk for developing lung cancer was found to increase
      in a cigarette dose-dependent manner across all combinations of genotypes.
      Furthermore, a 7- to 8-fold variation in risk was found among the various
      combinations; 3.2 in individuals with combined GSTM1(+) and CYP1A1(m2/m2) and
      21.9 in those with combined GSTM1(-) and CYP1A1(m2/m2) genotype when the smoking
      index (sigma cigarettes smoked per day x years of smoking) was set at > or = 800.
      The results suggest that individuals having CYP1A1(m2/m2) are relatively
      resistant to tobacco-related lung cancers when combined with GSTM1(+), but are
      highly susceptible when combined with GSTM1(-). Combined CYP1A1 and GSTM1
      genotype is thus a potential predictor of genetic susceptibility to smoking
      related lung cancers in populations where CYP1A1 m2 or Val alleles are common.

PMID- 7586132
TI  - Chemoprevention of urinary bladder carcinogenesis by the natural phenolic
      compound protocatechuic acid in rats.
AB  - The modifying effect of dietary administration of protocatechuic acid (PCA)
      during the initiation and postinitiation phases on N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis was investigated in
      male F344 rats. Animals were divided into nine groups and groups 1-7 were given
      0.05% BBN in drinking water for 6 weeks to induce bladder neoplasms. Rats in
      groups 2, 3 and 4 were fed diets containing 500, 1000 and 2000 p.p.m. PCA
      respectively for 8 weeks, starting 1 week before BBN exposure. Groups 5, 6 and 7
      were fed the PCA-containing diets at three dose levels for 33 weeks. Group 8 was
      fed the diet containing 2000 p.p.m. PCA alone throughout the study. Group 9 was
      given tap water without BBN and the basal diet without PCA and served as an
      untreated control. At 41 weeks after the start, all animals were killed. The
      incidence of bladder tumors and preneoplastic lesions, and cell proliferation
      activity estimated by the numbers of silver-stained nucleolar organizer regions
      proteins (AgNORs) and proliferating cell nuclear antigen (PCNA)-immunoreactive
      cells were compared among the groups. PCA administration at 1000 and 2000 p.p.m.
      during the initiation and postinitiation phases significantly decreased the
      carcinoma incidence in a dose-dependent manner. Also, PCA at all doses given
      during either initiation or postinitiation phases reduced the development of the
      preneoplastic lesions. PCA feeding significantly reduced the numbers of AgNORs
      and PCNA-positive cells in the non-lesional transitional epithelium,
      preneoplasms, and neoplasms in the urinary bladder of rats treated with BBN.
      These results indicate that dietary administration of PCA is quite effective in
      preventing BBN-induced bladder carcinogenesis.

PMID- 7586134
TI  - Species variation in the metabolism of 15,16-dihydro-11
      methylcyclopenta[a]phenanthren-17-one to its 3,4-dihydrodiol, the proximate
      carcinogen.
AB  - The title compound is a strong carcinogen, similar in potency to benzo[a]pyrene
      in mouse skin assay. This paper describes a comparison of its in vitro metabolism
      by hepatic microsomal preparations from mouse, rat, rabbit, hamster, dog, monkey
      and man. Metabolites were isolated by preparative high pressure liquid
      chromatography from the ethyl acetate extractable material and their structures
      tentatively assigned on the basis of their retention times and ultraviolet
      spectra, when possible by direct comparison with authentic synthetic specimens.
      Mass spectrometry was then used to confirm these assignments. All these animals
      produce the same range of metabolites derived exclusively from oxidation at the
      benzo-ring A, the five-membered ring D, and at the 11-methyl group. However, the
      amounts of individual metabolites varied substantially. In particular all the
      animals yielded the proximate carcinogen 3,4-dihydroxy-11-methyl-3,4,15, 16
      tetrahydrocyclopenta[a]phenanthren-17-one, from which it is reasoned that all
      might be susceptible to its carcinogenic action. A rationalization for the
      observed distribution of the metabolites is proposed on the basis of a molecular
      model of the active site of cytochrome P450 1A1, the oxidative enzyme involved.

PMID- 7586135
TI  - Styrene oxide-induced HPRT mutations, DNA adducts and DNA strand breaks in
      cultured human lymphocytes.
AB  - Styrene-7,8-oxide (SO) is the major in vivo metabolite of styrene, a widely used
      plastic monomer. SO has been classified as probably carcinogenic to humans. We
      studied the genotoxic effects of SO in human peripheral blood lymphocytes (PBL)
      in vitro. SO-treatment in the range of 0.05-0.6 mM for 24 h resulted in a dose
      dependent decrease of cell survival and increase of HPRT mutation, O6-guanine DNA
      adducts and DNA strand breaks, whereas higher concentrations caused pronounced
      cell death. SO was a weak mutagen, inducing at most 10-20 mutants per 10(6)
      clonable cells (approximately 4-fold over the background) after treatment with
      0.2-0.4 mM for 24 h or 6 days. The levels of DNA adducts in treated cells
      correlated with SO-concentrations, but only four adducts per 10(8) nucleotides
      were detected at the highest treatment concentrations. Yet, adducts were still
      detectable in cells that had been cultured for 6-8 days after treatment. SO
      induced DNA strand breaks, measured with the Comet assay, were detectable after 1
      h exposure to 0.05-0.1 mM. Post-treatment incubation for 24 h decreased the level
      of DNA strand breaks to the control level. There was no correlation between the
      levels of DNA adducts and frequency of HPRT mutation. The present results
      indicate that SO is relatively inefficient in inducing HPRT mutation and O6
      guanine DNA adducts in human lymphocytes in vitro, which may be related to its
      pronounced cytotoxicity at concentrations above 0.4 mM. A comparison with
      previous in vivo data obtained by the same assays in T-lymphocytes of styrene
      exposed workers suggests that chronic, low dose exposure to styrene in the work
      environment may be more efficient in inducing persistent DNA adducts and HPRT
      mutation than acute, short-term exposure.

PMID- 7586138
TI  - Normal human cells at confluence get heat resistance by efficient accumulation of
      hsp72 in nucleus.
AB  - We investigated the heat-sensitivity of normal human cells and cells derived from
      human cancers (cancer cells) heated at 43 degrees C under different culture
      conditions. Primary human cells which keep in contact with each other show heat
      resistance, but cancer cells do not. This does not correlate with the total
      cellular amount of heat shock protein 72, but rather with accumulation of the
      protein in the nucleus after heating.

PMID- 7586139
TI  - Dosimetry of O6-methylguanine in rat DNA after low-dose, chronic exposure to N
      nitrosodimethylamine (NDMA). Implications for the mechanism of NDMA
      hepatocarcinogenesis.
AB  - Groups of female Wistar Furth/NCr rats, aged 6 weeks or 7 months at the start of
      the experiment, were administered drinking water containing N
      nitrosodimethylamine (NDMA) for up to 28 days at concentrations in the range 0.2
      2.64 p.p.m., resulting in daily intakes in the range 28-372 micrograms/kg/day at
      age 10 weeks. The levels of the premutagenic DNA adduct O6-methylguanine (O6-meG)
      in liver and blood leukocyte DNA were measured at different times during this
      exposure as well as on the days immediately following cessation of exposure. The
      adduct was found to accumulate rapidly in both tissues, reaching within 2-7 days
      steady states in the range 0.08-0.45 mumol/molG, similar in young and adult
      animals. Accumulation of O6-meG in blood leukocytes was approximately 30% lower
      than in the liver. Following cessation of NDMA treatment, adducts were lost
      rapidly from the DNA of both tissues, with an apparent t1/2 of approximately 19
      23 h for the liver and 30-35 h for blood leukocytes. No change in liver O6
      alkylguanine-DNA alkyltransferase (AGT) took place throughout this treatment. The
      steady-state adduct levels were approximately linearly related to NDMA dose-rate,
      except that a clear break (corresponding to a 2.6-fold lower slope) was observed
      at dose rates > 0.4 p.p.m. (approximately 56 micrograms/kg/day). This dose
      response relationship is in contrast to the sharp increase in the liver tumour
      induction in rats chronically treated with similar concentrations of NDMA
      reported by Peto et al. (Cancer Res., 51, 6415-6451) and suggests that
      accumulation of O6-meG cannot by itself account for the hepatocarcinogenic
      efficacy of NDMA in the rat. Following i.g. administration of single doses of
      NDMA in a range approximately corresponding to the daily intake during the above
      mentioned chronic exposure study (25, 50 or 100 micrograms/kg), repair of O6-meG
      followed sharply biphasic kinetics in both liver and blood leukocytes. In the
      liver, an initial rapid phase (t1/2 approximately 1.5-1.7 h) was followed by much
      slower repair (t1/2 approximately 20.7-24.9 h) despite the absence of any change
      in AGT. Extrapolation of the two segments of the repair kinetics plots back to 0
      time suggests that approximately 52-61% of the adducts originally formed in the
      liver and 33-35% of those formed in blood leukocytes belonged to the rapidly
      repaired category.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7586136
TI  - Frequent mutations of the p53 gene and infrequent H- and K-ras mutations in
      urinary bladder carcinomas of NON/Shi mice treated with N-butyl-N-(4
      hydroxybutyl)nitrosamine.
AB  - To elucidate whether common genetic events in human urinary bladder
      carcinogenesis also occur in rodent models, we investigated the presence of p53,
      H- and K-ras mutations in 18 urinary bladder carcinomas induced by various
      concentrations of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male NON/Shi
      mice. Histopathologically, all were invasive, 11 being squamous cell carcinomas
      (SCCs) and the remaining seven being transitional cell carcinomas (TCCs). Using
      polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP)
      analysis followed by DNA sequencing, p53, H- and K-ras mutations were observed in
      14 (78%; exons 5-7), two (11%; one each on exons 1 and 2) and one (5.6%; exon 1)
      animals respectively. The frequencies of mutations in p53 exons 5, 6 and 7 were 7
      (39%), 4 (22%), and 9 (50%) respectively, and no mutation was found in exon 8.
      All mutations involved one base-pair substitution with or without amino acid
      changes and the types of base-pair substitution were random. No evident
      association was observed between mutation sites and the histological phenotypes.
      In conclusion, p53 mutations are frequent in BBN-induced mouse invasive urinary
      bladder tumors, at similar levels to those observed for human high-grade invasive
      carcinomas, and this plus their distribution suggests their possible
      participation in this model of urinary bladder carcinogenesis.

PMID- 7586137
TI  - Accumulation and persistence of DNA adducts of the synthetic steroid cyproterone
      acetate in rat liver.
AB  - Cyproterone acetate (CPA) is a synthetic steroid which is widely used in
      antiandrogenic and gestagenic drugs. We have recently shown that CPA induces DNA
      adducts in cultured rat hepatocytes and in rat liver (1). In the present
      investigation, we studied the persistence and accumulation of CPA-derived DNA
      adducts in the liver of rats using the 32P-postlabeling technique. To study the
      persistence of CPA-DNA adducts, rats were treated with a single oral dose of 10
      (female rats) or 100 mg CPA/kg body wt (male rats). Four DNA adducts were
      detected in the liver of both gender. In female rats, maximal total DNA adduct
      levels of 3.40 +/- 0.04 adducts/10(6) nucleotides were observed after 1 week.
      Eleven weeks later, 40% of the adducts determined after 1 week were still
      detectable. In male rats, maximal hepatic DNA adduct levels of approximately 98
      +/- 3/10(9) nucleotides were attained after 2 weeks. The adduct level decreased
      during the following 4 weeks to approximately 40% of the earlier observed maximal
      level. To study the accumulation of the CPA-DNA adducts, rats were treated daily
      with a low oral dose of 50 micrograms CPA/kg body wt for 42 days. During this
      treatment period, the level of the four adducts increased continuously from
      approximately 10 to approximately 380 adducts/10(9) nucleotides in the liver of
      female rats. DNA adducts were formed at much lower levels in male rats; only one
      type of DNA adduct was detectable, the level of which increased to approximately
      6 adducts/10(9) nucleotides after 42 days. In conclusion, CPA induces DNA adducts
      in rat liver; binding of the steroid is much higher in female compared to male
      rats. The CPA-DNA adducts show a high persistence and as a consequence of their
      long half life, CPA-DNA adducts accumulate significantly in the liver of rats.

PMID- 7586140
TI  - Molecular analysis of mutations induced by 2-chloroacetaldehyde, the ultimate
      carcinogenic form of vinyl chloride, in human cells using shuttle vectors.
AB  - Vinyl chloride (VC) is a carcinogen associated with human and animal cancers. The
      ultimate carcinogenic form of VC, 2-chloroacetaldehyde (CAA), has been suspected
      to be mutagenic and we confirmed the mutagenicity of CAA using a modified shuttle
      vector plasmid. Base sequence analyses of 109 mutant plasmids with mutations in
      the supF gene, which were treated with CAA and propagated in the cultured human
      cells, revealed that more than half of the single base substitutions were G:C to
      A:T transitions with eight hotspots. The majority of the mutations involving G:C
      base pairs were in 5'-AAGG-3' or 5'-CCTT-3' sequences suggesting that these
      sequences are the main targets of mutagenesis caused by CAA.

PMID- 7586142
TI  - Chromium(VI)-induced nuclear factor-kappa B activation in intact cells via free
      radical reactions.
AB  - Incubation of chromium(VI) [Cr(VI)] with cultured Jurkat cells resulted in
      activation of DNA binding activity of the nuclear factor (NF)-kappa B. In a
      combination with glutathione reductase, a Cr(VI) reducing agent, Cr(VI) expressed
      an enhanced activity in induction of NF-kappa B. This activation of NF-kappa B
      was decreased by a metal chelator, diethylene-triaminepentaacetic acid or
      catalase, but increased by superoxide dismutase. Addition of Mn2+, which reacts
      with Cr(IV) and inhibits Cr(IV)-mediated hydroxyl radical (.OH) generation via
      Fenton-like reaction, attenuated the activation of NF-kappa B. Sodium formate, an
      .OH radical scavenger, also inhibited the activation. Electron spin resonance
      measurements showed that the incubation of Cr(VI) with intact Jurkat cells
      generated reactive Cr(V) intermediate. Glutathione reductase and NADPH enhanced
      Cr(V) generation. Electron spin resonance spin trapping measurements using 5,5
      dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent provided evidence
      that the incubation of Cr(VI) with the Jurkat cells in the presence of
      glutathione reductase generated .OH radicals. H2O2 enhanced .OH radical
      generation and also enhanced Cr(V) formation, indicating the role of Cr(IV) in
      .OH radical generation. We conclude that Cr(VI) can activate NF-kappa B in vitro
      via Cr(IV)-mediated free radical reactions. We hypothesize that Cr(VI)-mediated
      NF-kappa B activation may be involved in the mechanism of Cr(VI)-induced
      carcinogenicity.

PMID- 7586141
TI  - Standardization of counting micronuclei: definition of a protocol to measure
      genotoxic damage in human exfoliated cells.
AB  - The proportion of exfoliated buccal mucosal cells with micronuclei gives the
      opportunity to assess sensitivity to gamma-radiation and genotoxic compounds and
      in addition to monitor the effectiveness of cancer intervention strategies. So
      far, results on counting micronuclei in various publications are difficult to
      compare because of differences in methods used, especially with regard to
      microscopical magnification used and number of cells counted. The aims of this
      study were (i) to define a protocol for counting micronuclei; (ii) to assess the
      feasibility of manually counting micronuclei; and (iii) the assessment of inter-
      and intra-patient variability of the number of micronuclei. We propose the
      definition of a strict protocol on counting micronuclei, with regard to
      cytological preparation, definition of micronuclei, instrumentation, sampling of
      cells in a cytological specimen and sample size. Such a strict protocol is a
      prerequisite for counting micronuclei in exfoliated cells to get a reproducible
      and sensitive indicator of exposure and for cancer risk. Although the inter- and
      intra-observer reproducibility of counting micronuclei per 1000 cells using such
      a protocol is well, we show that the variability among 10 assessments of
      micronuclei per 1000 cells taken sequentially from a sample size of 10,000 nuclei
      of the same specimen can be enormous (coefficients of variation varied in seven
      individuals studied between 42.1 and 102.9%). Based on the observed low
      frequencies varying from 1.2 to 5.2 micronuclei per 1000 cells and the variation
      found, we conclude that at least 10,000 exfoliated cells should be screened to
      monitor a significant reduction of 50% in the number of micronuclei (for a
      patient with an initial frequency in the micronuclei frequency range given).
      Since it takes approximately 7 h to evaluate this number of cells, it is also
      concluded that counting of micronuclei requires automation.

PMID- 7586143
TI  - Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ
      and carcinomas by the injection of sexually immature female rats with 1-methyl-1
      nitrosourea.
AB  - While most data in the literature indicate that chemically-induced mammary
      carcinogenesis in the rat proceeds through morphologically identifiable stages,
      little quantitative data exist on the frequency of their occurrence. A carcinogen
      induction protocol is reported that defines conditions under which approximately
      38% of detectable lesions in the abdominal-inguinal mammary glands were
      histologically classified as either intraductal proliferations or ductal
      carcinoma in situ. The remainder of the lesions were classified as carcinomas.
      This response was observed in a group of 30 female Sprague-Dawley rats injected
      i.p. with 50 mg 1-methyl-1-nitrosourea (MNU)/kg body wt at 21 days of age. The
      experiment was terminated 35 days following carcinogen administration. The
      methods used to prepare whole mounts and to identify, excise and process lesions
      in the whole mounts to permit histological classification are described in
      detail. This carcinogenesis protocol also induced a significant palpable tumor
      response. The first palpable tumor, histologically classified as an
      adenocarcinoma, was observed 30 days post carcinogen administration. When the
      experiment was terminated (35 days post MNU), the cumulative incidence of
      palpable carcinomas was 60%. The rapidity of the carcinogenic response was
      remarkable. Unlike the i.v. administration of 7,12-dimethylbenz[a]anthracene
      (DMBA) to rats of this age, MNU injection resulted in > 99% incidence of palpable
      mammary gland tumors that were malignant. The data reported in this paper confirm
      and support the pathogenetic pathway described for the induction of mammary
      tumors in the rat by DMBA. The induction of mammary carcinogenesis in immature
      animals described in this paper may be of value in the investigation of early
      morphologically identifiable stages of this disease process as well as providing
      an extremely rapid method for tumor induction.

PMID- 7586144
TI  - Differential response of normal and HPV immortalized ectocervical epithelial
      cells to B[a]P.
AB  - Cigarette smoking has been established as a risk factor for the development of
      cervical cancer. Polycyclic aromatic hydrocarbons such as benzo[a]pyrene (B[a]P),
      which are present in cigarette smoke, might account for this increased risk. The
      effects of B[a]P on cell growth, aryl hydrocarbon hydroxylase, DNA adducts and
      p53 levels was measured in cervical cells. Since 90% of cervical preneoplastic
      lesions are positive for the human papillomavirus (HPV) we compared the effects
      of these chemicals in normal ectocervical epithelial cells (ECE) and human
      papillomavirus 16 (HPV16) immortalized ectocervical epithelial cells (ECE16-1).
      Exposure of normal ECE and HPV immortalized ECE16-1 cells to B[a]P inhibited cell
      proliferation. Inhibition occurred at 20-fold lower concentrations in the normal
      ECE cells compared to ECE16-1 cells. The proliferation of cervical cells which
      express mutated p53 was unaffected by B[a]P. Neither cervical stromal cells nor
      endometrial stromal cells were affected by these compounds. The effects of B[a]P
      on normal ECE cell proliferation correlated with increased terminal
      differentiation as measured by increased envelope formation. In contrast, B[a]P
      exposure did not induce envelope formation in immortalized ECE16-1 cells or in
      cervical tumor cells. Pretreatment of both ECE and ECE16-1 cells with 2,3,7,8
      tetrachlorodibenzo-p-dioxin, which induces P450 expression and activity, did not
      alter B[a]P metabolism in either normal or immortalized cells. Furthermore,
      equivalent levels of DNA adducts were formed by B[a]P in ECE and ECE16-1 cells.
      Neither the extent of adduct formation nor the rate of their removal differed in
      normal and immortalized cervical cells. Therefore, the diminished growth
      inhibition of the ECE16-1 cells as compared to normal ECE cells by B[a]P is not
      due to changes in cytochrome P450 of the 1A family metabolism or DNA adduct
      number. Furthermore, analysis of the p53 levels in both normal and ECE16-1 cells
      revealed that p53 levels are higher in normal versus immortalized ectocervical
      cells, and p53 is induced in both cell types following B[a]P treatment. Thus
      reduced p53 levels in ECE16-1 cells may contribute to a lack of growth
      suppression following B[a]P treatment. These results demonstrate that HPV16
      immortalization diminishes ectocervical epithelial cell responsiveness to
      toxicant damage (i.e. decreased cell proliferation and increased terminal
      differentiation). As a result, ECE16-1 cells that sustain genotoxic damage which
      leads to DNA adduct formation continue to proliferate and may be at increased
      risk for mutations and further progression towards a fully transformed phenotype.

PMID- 7586145
TI  - Phenobarbital promotes the development of adenocarcinomas in the accessory sex
      glands of MNU-inoculated L-W rats.
AB  - Aged Lobund-Wistar (L-W) rats develop: (i) spontaneous and induced metastasizing
      adenocarcinomas in the prostate and seminal vesicle (P-SV) complex; and (ii)
      spontaneous hepatomas and hepatocarcinomas. Within the time-frame of 14 months,
      similar adenocarcinomas were induced in the P-SV complex in 70-90% of younger L-W
      rats by a single i.v. inoculation of methylnitrosourea (MNU) which was followed
      by slow release s.c. implants of testosterone propionate (TP). Within the same
      time-frame, neither MNU nor TP alone induced significant incidences of P-SV
      tumors; and untreated control L-W rats were disease-free. Methylnitrosourea or TP
      and combinations thereof did not induce liver tumors. However, when MNU
      inoculated L-W rats were fed phenobarbital (PB), they developed (i) metastasizing
      adenocarcinomas in the P-SV complex and (ii) altered cellular foci and nodules in
      the livers. Methylnitrosourea induced a high incidence of benign lung adenomas
      which progressed to lung cancers in numbers which were of marginal significance.
      Thus, dormant MNU-initiated cells in the P-SV complex were activated by
      phenobarbital, to produce adenocarcinomas in that complex.

PMID- 7586146
TI  - Altered expression of cyclins and c-fos in R6 cells that overproduce PKC epsilon.
AB  - Since PKC epsilon functions as an oncogene when stably overexpressed in R6 rat
      fibroblasts (Cacace et al. 1993) in the present study we examined whether
      transformed R6-PKC epsilon cells display abnormalities in the expression of
      specific early response and cyclin genes. When vector control and R6-PKC epsilon
      cells were starved of serum for 72 h they arrested in G0/G1 and showed passage
      through the cell cycle at similar rates after subsequent stimulation with 10%
      fetal calf serum plus TPA. In PKC epsilon cells, induction of cyclin D1 protein
      was markedly reduced, and that of cyclin A was slightly reduced when compared to
      control cells. Northern blot analyses indicated that decreased expression of
      cyclin D1 and A protein in PKC epsilon cells is due to translational or post
      translational effects. A study of early response gene expression in PKC epsilon
      cells indicated that there was a marked reduction in the expression of c-fos mRNA
      but not in c-jun or c-myc mRNAs. The marked decreases in cyclin D1 and c-fos
      expression seen in PKC epsilon cells were not seen in R6 cells that overexpress
      PKCs alpha or beta. These findings suggest that PKC epsilon cells bypass certain
      normal signal transduction and cyclin-controlled pathways involved in cell
      proliferation.

PMID- 7586147
TI  - Differential in vivo mutagenicity of the carcinogen/non-carcinogen pair 2,4- and
      2,6-diaminotoluene.
AB  - The aromatic amines 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT)
      are structural isomers that have been extensively studied for their mutagenic and
      carcinogenic characteristics. Both compounds are equally mutagenic in the
      Ames/Salmonella assay in the presence of S9. However, the differences in the
      results of chronic rodent carcinogen bioassays using these two compounds are
      significant, in that 2,4-DAT is a potent hepatocarcinogen, whereas 2,6-DAT does
      not produce an increased incidence of tumors in rats or mice at similar doses.
      The Big Blue transgenic B6C3F1 mouse carries multiple copies of bacteriophage
      lambda, each with a lacI mutational target gene, integrated into mouse chromosome
      4. Our studies were designed to determine whether the Big Blue system could be
      used to detect differences in the in vivo mutagenic activity between the
      carcinogen/non-carcinogen pair 2,4- and 2,6-DAT and to determine whether the in
      vivo mutagenesis assay results correspond to the rodent carcinogen bioassay
      results. Male B6C3F1 transgenic mice were exposed to 2,4- or 2,6-DAT at 0 or 1000
      p.p.m. in the diet for 30 and 90 days. Mice serving as positive controls were
      administered five daily i.p. injections of 6 mg/kg dimethylnitrosamine (DMN) in
      saline and were sacrificed 15 days following the last injection. Mutant
      frequencies at lacI were determined by recovering the genomically integrated
      lambda phage using an in vitro packaging reaction followed by infection of an
      appropriate Escherichia coli host. Complete non-sectored blue mutant plaques were
      scored against a background of clear non-mutant plaques. Mutant frequencies were
      nearly identical for all three groups at 30 days, while at 90 days the mutant
      frequency for the hepatocarcinogen 2,4-DAT (12.1 +/- 1.4 x 10(-5)) was
      significantly higher (P < 0.01) as compared with both age-matched (spontaneous)
      controls (5.7 +/- 2.9 x 10(-5)) and the 2,6-DAT-exposed group (5.7 +/- 2.4 x 10(
      5)). Mutations at lacI arising ex vivo during replication in E. coli are observed
      in this system as sectored blue plaques. The sectored plaque frequency in this
      study was constant across all groups at approximately 9.0 x 10(-5). Results from
      this study demonstrate that the Big Blue transgenic mutation assay: (i) can
      distinguish differences in vivo between the mutagenic responses of a carcinogen
      and a non-carcinogen which elicited comparable mutagenic activity in
      S.typhimurium; (ii) is sensitive to mutagens through subchronic dietary exposure;
      and (iii) yields a differential response depending upon the length of time mice
      are exposed to a mutagen.

PMID- 7586148
TI  - p53 expression in normal versus transformed mammalian cells.
AB  - To answer the question whether the level of p53 expression also reflects the
      status of a cell, with reference to transformation and genome stability, we have
      examined, by immunocytochemistry, the presence of p53 protein in a number of cell
      types including human diploid cells, Chinese hamster embryonal cells at different
      passages and gene amplified and/or transformed Chinese hamster cell lines.
      Primary human fibroblasts at early passage (LEO) and an established, non
      transformed, Chinese hamster cell line at early passage (CHEF/18) did not show
      any detectable p53 expression, either nuclear or cytoplasmic. All transformed
      human (Raji) and Chinese hamster cell lines (CHO, V79, V79/B7) showed a nuclear
      expression of p53, although at different intensities. Two cell lines selected
      from V79/B7 for their resistance to phosphonacetyl-L-aspartate or methotrexate
      and previously shown to bear gene amplification, showed p53 expression. In PALA L
      cells p53 expression was nuclear as in other positive cell lines tested, while in
      MTX M cells it was cytoplasmic. CHEF/18 cells at late passage in culture showed
      the typical behaviour of transformed cells and p53 was detected in several cells.
      Moreover, when transformed CHO cells were treated with compounds known to induce
      reverse transformation, both the disappearance of hallmarks of transformed
      phenotype and p53 reduction were observed. These results indicate a strong
      association within the same cell type between p53 expression and transformed
      status.

PMID- 7586149
TI  - A polymorphism at codon 160 of human O6-methylguanine-DNA methyltransferase gene
      in young patients with adult type cancers and functional assay.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in repair
      of alkylating agent-induced DNA damage. Among the alkylation products of DNA, O6
      methylguanine is one of the most critical lesions leading to the induction of
      mutations. The enzyme MGMT transfers the methyl group from O6-methylguanine of
      DNA to its own cysteine residue. Although mutations of other DNA repair genes
      involved in nucleotide excision repair and mismatch repair have been proven to be
      related to human tumorigenesis, the question of whether MGMT gene mutation might
      play a role in human carcinogenesis has hitherto not been elucidated. If there is
      a population with decreased enzyme activity due to defective MGMT gene, the
      affected individuals should be at risk of developing cancer early in life because
      of an increased susceptibility to alkylating agents. To test this hypothesis,
      germ line mutations of the MGMT gene were investigated in 12 young patients with
      adult type cancers (mean, 16.7 years old, 8 hepatocellular carcinomas, 3 gastric
      cancers, 1 cholangiocellular carcinoma) and 28 elderly patients who died of non
      cancer diseases as controls (mean, 66 years old). A point mutation at codon 160
      in exon 5, GGA to AGA, converting glycine to arginine was found in three of the
      young patients (25%), while the same mutation was found in three out of 28
      (10.7%) in the control group. The mutated codon was located 15 codons from a
      functional cysteine residue toward the carboxyl terminal. Investigation of enzyme
      function, even in cases of bi-allelic mutation, revealed comparable activities
      for both mutated and wild type MGMT. Thus, we conclude the mutation is a normal
      polymorphism of the MGMT gene, present in approximately 15% of the population,
      although this does not rule out a possible influence in other tissues.

PMID- 7586150
TI  - Cisplatin- and carboplatin-DNA adducts: is PT-AG the cytotoxic lesion?
AB  - In order to determine the nature of the cytotoxic lesion(s) formed by the
      antitumour drugs cisplatin and carboplatin, a comparative study was made of
      bifunctional DNA-adduct formation by these drugs. The kinetics of bifunctional
      cisplatin adduct formation were studied with DNA in vitro and in cultured Chinese
      hamster ovary (CHO) cells. Prior to adduct measurements with AAS in in vitro
      platinated DNA and with ELISA in cellular DNA, the monoadducts were inactivated
      with thiourea (10 mM; 1 h at 37 degrees C). The data indicated that the
      conversion of monofunctional to bifunctional adducts, with t1/2 of approximately
      2 h (37 degrees C), leads to maximum intrastrand adduct levels after
      approximately 4-6 h postincubation. This interval coincided with the period
      during which the cytotoxic effect of cisplatin could be reduced by a 1 h 10 mM
      thiourea post-incubation of the cells. The formation of interstrand crosslinks
      continued for approximately 7 h of post-incubation; then these amounted to
      approximately 2% of the total DNA adducts. When a DNA sample was dialysed against
      0.1 M NH4HCO3 (16 h, 37 degrees C) immediately after cisplatin treatment, in
      order to block mono- to bifunctional adduct conversion, adduct levels were found
      similar to those after the 4-6 h post-incubation. From this it is clear that the
      high values reported earlier for bifunctional cisplatin adducts in such DNA
      samples are not correct. These values apparently represent the amounts of adducts
      that eventually would have been formed during post-incubation in DNA in vitro but
      also in cells in the absence of cellular repair. The cisplatin data of CHO cells
      were compared with those after treatment of the cells with equitoxic doses of
      carboplatin. The data indicate that after 12 h post-incubation, when all
      bifunctional adducts are formed, the total amount of the various bifunctional
      adducts after cisplatin treatment (37.5 +/- 4.5 fmol/micrograms DNA) was in the
      same range as that after carboplatin (32.8 +/- 6.3 fmol/micrograms DNA). However,
      because the relative occurrences of the adducts were different, it could also be
      concluded that if one of the diadducts were exclusively responsible for the
      cytotoxic effect of these platinum antitumour drugs, Pt-AG is the only likely
      candidate.

PMID- 7586152
TI  - Fluorescence spectroscopic identification of 7,12-dimethylbenz[a]anthracene
      induced hamster buccal pouch carcinogenesis.
AB  - An attempt was made to study whether light-induced fluorescence spectroscopy
      could be exploited to discriminate premalignant and malignant tissues of hamster
      buccal pouch carcinogenesis from normal tissues during a 16 week regimen of tri
      weekly topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in liquid
      paraffin. Histologically, the DMBA-treated buccal mucosa showed hyperplastic
      changes at 4-6 weeks, papillomas at 8-10 weeks, early invasive carcinomas at 11
      13 weeks and finally well-differentiated squamous cell carcinomas at 14-16 weeks
      of treatment. Acetone extracts of these different staged tissues with age matched
      control tissues were excited at 405 and 420 nm and the emissions were scanned
      from 430 and 440 to 700 nm respectively. The spectral profiles of control and
      transformed tissues were found to be different, each displaying their own
      characteristic prominent maxima and other spectral marks. The spectra of
      transformed tissues showed characteristic peaks around 620-630 nm which did not
      appear in control tissues and the fluorescent intensities at 630 nm [FI(630)nm]
      were significantly increased from early stages onwards when compared to controls.
      The spectra of DMBA carcinomas developed at the 18th week after withdrawal of
      DMBA application at the 10th week and carcinoma extract spiked with DMBA
      confirmed the peak around 620-630 could be attributed only to porphyrin compounds
      accumulated in transformed tissues. Furthermore, the ratios of
      FI(520)nm/FI(630)nm of transformed tissues were also significantly decreased when
      compared to control tissues. This diagnostic test had a very close resemblance
      with respect to histological studies. These results suggest that this technique
      using conventional light-induced fluorescence spectroscopy may be useful for
      early diagnosis of premalignant and malignant lesions of oral cavity.

PMID- 7586151
TI  - Substitution of equally carcinogenic UV-A for UV-B irradiations lowers epidermal
      thymine dimer levels during skin cancer induction in hairless mice.
AB  - Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions induced by UV
      B radiation, among these lesions thymine dimers are most frequent. Although UV-A
      radiation may also induce CPD, it has been found that equally cytotoxic or
      equally mutagenic UV-A and UV-B doses do not induce equal amounts of CPD,
      indicating that other DNA adducts contribute to the UV-A effects. Thus far it has
      not been established whether this finding can be extrapolated and also holds true
      for the more complex biological endpoint of skin cancer. Therefore, we compared
      thymine dimer levels during skin cancer induction by combined UV-A and UV-B daily
      exposures with the levels from equally carcinogenic daily UV-B exposures. From
      control experiments it was known that both groups would react similarly regarding
      the occurrences of carcinomas, with a median latency time of 170 +/- 10 days.
      After 50, 106 and 151 days of irradiation eight hairless mice (SKH:HR1) from both
      groups were euthanized and thymine dimers in epidermal cell suspensions were
      quantified by flow cytometry. Staining on DNA content enabled us to quantify
      thymine dimers in G0/G1-phase, in S-phase and in G2M-phase subpopulations. Both
      in total epidermal cell populations and in subpopulations of replicating
      epidermal cells thymine dimer levels were significantly lower in the UV-A/B
      combination group than in the UV-B group (0.010 < P < 0.025 and P < 0.005
      respectively). This indicates that the carcinogenicity of UV-A relative to that
      of UV-B is not properly measured by thymine dimers and that other DNA lesions
      than CPD, for example, from reactive oxygen species, are likely to contribute to
      UV-A carcinogenicity.

PMID- 7586153
TI  - Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis or
      tumorigenesis by vinyl carbamate and N-nitrosodimethylamine.
AB  - Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent and
      irritating ingredient of hot chilli peppers, which are frequently consumed as
      spices. This dietary phytochemical has been found to interact with microsomal
      xenobiotic metabolizing enzymes in rodents. Capsaicin and its saturated analog
      dihydrocapsaicin (trans-8-methyl-N-vanillyl-6-nonanamide) have been proposed to
      inactivate cytochrome P-450 HE1 by irreversibly binding to the active sites of
      the enzyme. Besides cytochrome P-450 HE1, other isoforms of the P-450 superfamily
      were also reported to be inhibited by capsaicin. The inhibition by capsaicin of
      microsomal monooxygenases involved in carcinogen activation implies its
      chemopreventive potential. As part of a program to investigate chemoprotective
      properties of capsaicin we initially determined the effect of capsaicin on vinyl
      carbamate (VC)- and N-nitrosodimethylamine (NDMA)-induced mutagenesis in
      Salmonella typhimurium TA100. Capsaicin (0.42 mM) attenuated the bacterial
      mutagenicity of VC and NDMA by 50% and 42% respectively. Diallyl sulfide, a
      thioether found in garlic with selective P-450 HE1 inhibitory activity, also
      lessened the mutagenicity of the above carcinogens in a concentration-dependent
      manner. The suppression of VC- and NDMA-induced mutagenesis by capsaicin and
      diallyl sulfide correlated with their inhibition of P-450 IIE1-mediated p
      nitrophenol hydroxylation and NDMA N-demethylation. Pretreatment of female ICR
      mice with a topical dose of capsaicin lowered the average number of VC-induced
      skin tumors by 62% at 22 weeks after promotion. A similar degree of protection
      was attained with oral administration of diallyl sulfide before carcinogen
      treatment. The results of this study suggest that capsaicin and diallyl sulfide
      suppress VC- and NDMA-induced mutagenesis or tumorigenesis in part through
      inhibition of the cytochrome P-450 IIE1 isoform responsible for activation of
      these carcinogens.

PMID- 7586154
TI  - Enhancement of esophageal carcinogenesis in male F344 rats by dietary phenylhexyl
      isothiocyanate.
AB  - The purpose of this study was to evaluate the potential effects of dietary 6
      phenylhexyl isothiocyanate (PHITC) on N-nitrosomethylbenzylamine (NMBA)-induced
      esophageal carcinogenesis in rats. Groups of 15 male F344 rats received weekly
      s.c. injections of NMBA in 20% dimethylsulfoxide or the vehicle alone for 15
      consecutive weeks. Two weeks prior to initiation of carcinogen or vehicle
      injections rats were provided with modified AIN-76A diet or modified AIN-76A diet
      containing PHITC at levels of 0.4, 1.0 or 2.5 mumol/g diet. Experimental controls
      consisted of groups that received only the vehicle (vehicle controls), NMBA
      (carcinogen controls) or PHITC at the high dose level of 2.5 mumol/g diet. No
      esophageal tumors or preneoplastic lesions were detected in rats that received
      the vehicle or PHITC alone. In contrast, all rats treated with NMBA alone or
      PHITC + NMBA exhibited esophageal tumors and preneoplastic esophageal lesions. In
      groups that received PHITC + NMBA tumor multiplicity was increased by 21-69% when
      compared with rats treated with NMBA alone, indicating that PHITC enhanced
      esophageal tumorigenesis in this model system. These results, in conjunction with
      our previous work, demonstrate that arylalkyl isothiocyanates may inhibit or
      enhance esophageal tumorigenesis in the NMBA-treated rat. The ability of
      isothiocyanates to inhibit or enhance experimental tumorigenesis may depend on
      alkyl chain length of the isothiocyanate, the animal species examined and the
      specific carcinogen employed.

PMID- 7586156
TI  - K-ras mutations in lung tumors from A/J and A/J x TSG-p53 F1 mice treated with 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone and phenethyl isothiocyanate.
AB  - The purpose of this study was to evaluate the effects of the loss of a p53 allele
      and phenethyl isothiocyanate (PEITC) pre-treatment on the tumorigenicity of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and K-ras mutation frequency
      in a hybrid mouse model. Male TSG-p53 'knock-out' mice were bred with A/J female
      mice to produce (A/J x TSG-p53) F1 mice either homozygous (p53+/+) or
      heterozygous (p53+/-) for p53 alleles. These mice, together with female A/J mice,
      were treated at 6-8 weeks of age with NNK or dosed with PEITC prior to
      administration of NNK. The A/J mice treated with NNK had a 100% incidence of lung
      tumors, with 9.7 +/- 3.4 tumors/mouse. A/J mice pre-treated with PEITC prior to
      NNK administration had 3.5 +/- 2.1 lung tumors/animal, although the incidence
      remained at 100%. In (A/J x TSG-p53) F1 mice with either the p53(+/-) or p53(+/+)
      genotype PEITC pre-treatment significantly decreased tumor incidence (100 to 40
      and 36%, respectively) and multiplicity (2.0 +/- 0.5 to 0.5 +/- 0.4 and 2.1 +/-
      0.5 to 0.5 +/- 0.4, respectively), indicating that PEITC is an effective
      chemopreventive agent in both A/J mice and (A/J x TSG-p53) F1 mice. Analysis of
      lung tumor DNA from A/J mice treated with NNK or NNK/PEITC indicated that 15 of
      17 (88%) and 20 of 23 (87%) of the tumors, respectively, contained G-->A
      transitions at the second base of codon 12 in the K-ras gene. Similarly, in lung
      tumors from (A/J x TSG-p53) F1 mice treated with NNK or NNK/PEITC 29 of 30 (96%)
      and 9 of 10 (90%), respectively contained G-->A transitions at the second base of
      codon 12 of the K-ras gene. No mutations of the p53 gene were found in any of the
      tumors analyzed, suggesting minimal involvement of this gene in the development
      of lung adenomas. These data indicate that absence of a p53 allele in (A/J x TSG
      p53) F1 mice does not alter the incidence or multiplicity of NNK-induced lung
      tumors and that PEITC inhibition of NNK tumorigenesis does not affect the
      frequency or spectrum of K-ras gene mutations found consistently with NNK
      carcinogenesis.

PMID- 7586158
TI  - Quantitative analysis of multiple phenotype enzyme-altered foci in rat
      hepatocarcinogenesis experiments: the multipath/multistage model.
AB  - The promotional effect of phenobarbital and 1-hydroxymethyl-pyren on enzyme
      altered lesions in the rat liver were quantified within the framework of two
      separate multipath/multistage models. The experiment analyzed followed an
      initiation-promotion protocol in which female Wistar rats were initiated with a
      single dose of diethylnitrosamine at 0.15 mumol/g body wt followed by a 3 week
      treatment-free period. A promotor, 1-hydroxymethyl-pyren or phenobarbital was
      then administered continuously in the diet for 120 days. All animals were
      sacrificed 3 weeks after treatment and their livers were examined for enzyme
      histological changes. Focal lesions were classified into three phenotype
      categories: adenosine triphosphatase altered (ATPase), sulfotransferase altered
      (ST) and jointly altered lesions (ATPase and ST). Quantitative methods were used
      to analyze the data, which consisted of the number and sizes of these enzyme
      altered lesions. Both multipath/multistage models fitted to the data clearly
      demonstrate that phenobarbital promotion produced more observable and larger foci
      than promotion via 1-hydroxymethyl-pyren and that the growth kinetics of the
      jointly altered lesions were elevated relative to the lesions expressing a single
      marker. It was not possible with these data to determine if there was a
      predominant sequence in the formation of jointly altered lesions.

PMID- 7586155
TI  - N-(4-hydroxyphenyl)retinamide (4-HPR)-mediated biological actions involve
      retinoid receptor-independent pathways in human breast carcinoma.
AB  - Retinoid response pathways involve retinoic acid receptors (RARs) and retinoid X
      receptors. N-(4-hydroxyphenyl) retinamide (4-HPR), a derivative of all-trans
      retinoic acid (RA) is currently in clinical trials as a chemopreventive agent for
      breast cancer. The issue whether 4-HPR mediates its biological actions via
      classical retinoid receptor pathways remains to be investigated. In this study,
      we provide several lines of evidence that 4-HPR mediates its biological actions
      via a novel pathway(s) that does not involve the classical retinoid receptor
      pathways. For example, 4-HPR was more potent than RA as an antiproliferative
      agent and inhibited growth of otherwise RA-resistant human breast carcinoma
      cells. Exposure to 4-HPR resulted in the generation of DNA fragmentation with
      subsequent cell death in both RA-positive estrogen receptor (ER)-positive as well
      as RA-refractory ER-negative breast carcinoma cell lines. N-(4
      Methoxyphenyl)retinamide (4-MPR), which is the major 4-HPR metabolite in
      circulation, was biologically inert in this system. 4-HPR and 4-MPR bound poorly
      to the RAR alpha, beta and gamma in vitro and only minimally activated the
      retinoic acid receptor element (RARE) and retinoid X receptor response elements
      (RXREs) in human breast carcinoma cells. Neither 4-HPR nor 4-MPR are metabolized
      to any of the known conventional retinoids. In addition, 4-HPR or 4-MPR
      transactivation of RAREs or RXREs transfected into MCF-7 and MDA-MB-231 cells was
      not noted at 48 h. Nevertheless 4-HPR-mediated cell death was observed at 48 h,
      further suggesting that neither 4-HPR nor 4-MPR are metabolized to retinoids
      which activate the RAREs or RXREs in breast carcinoma cells. Furthermore, unlike
      RA, which exhibited anti-AP1 activity, 4-HPR inhibition of growth did not involve
      anti-AP1 activity. These results suggest that 4-HPR acts by a unique pathway that
      is not mediated by retinoid receptors.

PMID- 7586157
TI  - Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and
      tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor
      promotion.
AB  - Commercial grade curcumin (approximately 77% curcumin, 17% demethoxycurcumin and
      3% bisdemethoxycurcumin) is widely used as a yellow coloring agent and spice in
      foods. In the present study topical application of commercial grade curcumin,
      pure curcumin or demethoxycurcumin had an equally potent inhibitory effect on 12
      O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in ornithine
      decarboxylase activity and TPA-induced tumor promotion in 7,12
      dimethylbenz[a]anthracene-initiated mouse skin. Bisdemethoxycurcumin and
      tetrahydrocurcumin were less active. In additional studies we found that
      commercial grade curcumin, pure curcumin, demethoxycurcumin and
      bisdemethoxycurcumin had about the same potent inhibitory effect on TPA-induced
      inflammation of mouse ears, as well as TPA-induced transformation of cultured JB6
      (P+) cells. Tetrahydrocurcumin was less active. The results indicate that pure
      curcumin and demethoxycurcumin (the major constituents of commercial grade
      curcumin) have the same potent inhibitory effects as commercial grade curcumin
      for inhibition of TPA-induced tumor promotion, but bisdemethoxycurcumin and
      tetrahydrocurcumin are less active.

PMID- 7586161
TI  - Inhibitory effect of dietary 4-ipomeanol on DNA adduct formation by the food
      mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in male CDF1 mice.
AB  - The food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is carcinogenic in
      the CDF1 mouse liver, lungs and stomach. IQ is activated to its ultimate
      carcinogenic form by N-hydroxylation, catalyzed principally by hepatic microsomal
      cytochrome P450IA2, and further esterification, resulting in the formation of N
      (deoxyguanosin-8-yl)-IQ and other adducts. The furanoterpenoid 4-ipomeanol (IPO)
      is a naturally occurring pneumotoxin which exerts its specific toxicity in Clara
      cells of the lung after activation by microsomal cytochrome P450. Because IPO is
      activated in the liver by a cytochrome P450IA2 enzyme, we evaluated IPO as a
      possible chemopreventive agent by assessing its ability to inhibit IQ-DNA adduct
      formation in the CDF1 mouse. Mice were put on an AIN-76A diet with or without
      0.075% IPO from day 0 to 54. IQ (0.01%) was added to the diets from day 22 to 41
      and animals were killed (four animals/time point) on days 42, 44, 46, 48, 50 and
      54. Blood (for white blood cell isolation), liver, lungs, stomach, small
      intestine, cecum, colon, kidneys, spleen and heart were collected for analysis of
      IQ-DNA adducts by 32P-post-labeling. During the 12 day period after cessation of
      IQ exposure (days 42-54) IQ-DNA adduct formation was significantly inhibited in
      the liver (33.6-46.4%), lungs (29.9-58.6%), stomach (33.2-51.5%) and white blood
      cells (24.5-63.7%), but not in the other organs. Except in the colon, adduct
      removal from organs during days 42-54 was relatively slow (36.0-81.9% of day 42
      levels remaining on day 54, 9.4-16.7% in the colon), but the presence of IPO in
      the diet did not influence the rate of adduct removal. Measurement of hepatic
      microsomal ethoxyresorufin deethylase, an activity specific for cytochrome P450IA
      isozymes, showed that the enzyme could be inhibited (14.1-68.1%) by IPO (0.05
      10.0 mM) in vitro. It is concluded that IPO inhibits IQ-DNA adduct formation in
      target organs of the CDF1 mouse and that IPO may act by inhibiting N
      hydroxylation of IQ. It is therefore possible that IPO may be a candidate
      chemopreventive agent against IQ-induced carcinogenesis.

PMID- 7586160
TI  - Characterization of human buccal epithelial cells transfected with the simian
      virus 40 T-antigen gene.
AB  - Serum-free cultures of normal human buccal epithelial cells were transfected with
      a plasmid containing the SV40 T-antigen (SV40T) gene. Two major lines developed
      that showed extended lifespans (between 30 and 40 weeks) as compared with the
      controls (approximately 6 weeks). Continued growth through one or two crises
      generated several sublines. They expressed the epithelial marker keratin and also
      exhibited nuclear expression of SV40T. The lines showed abnormal karyotypes with
      both numerical and structural aberrations and variably responded to agents that
      normally inhibit growth and/or induce terminal differentiation, i.e. transforming
      growth factor-beta 1 and fetal bovine serum. One of the lines, termed SVpgC2a,
      developed into an apparently immortal line, since it had undergone more than 700
      population doublings from over 2 years in culture. Further characterization of
      this line demonstrated its clonal origin, with integration of two copies of SV40T
      at the same site and the presence of both normal retinoblastoma and wild-type p53
      proteins. This line showed high resistance to growth inhibition by transforming
      growth factor-beta 1 and serum similar to that shown by buccal carcinoma cell
      line SqCC/Y1. Neither SVpgC2a nor its parental lines were tumorigenic when
      injected into athymic nude mice, whereas the SqCC/Y1 cells induced tumors. The
      various lines with extended but finite lifespans, complemented by one
      immortalized line, which retained non-malignant properties upon extended culture,
      provide a battery of model systems that will be useful for studying mechanisms of
      human oral carcinogenesis.

PMID- 7586159
TI  - Mouse mammary hyperplasias and neoplasias exhibit different patterns of cyclins
      D1 and D2 binding to cdk4.
AB  - Deregulated expression of G1 cyclins D1 and D2 is a feature of some neoplasias.
      This study examined the altered expression of D1 and D2 cyclins, both the total
      pool and as associated with cdk4 and cdk2, at different stages of mouse mammary
      tumorigenesis. Three different mammary hyperplastic outgrowth lines, TM2, TM10
      and TM12, and their respective tumors were examined. Increasing levels of the
      cyclin D1 protein pool, D1 binding to cdk4 and cdk2 and cdk4 kinase activity were
      closely correlated with tumorigenesis. In constrast, cyclin D2 binding to cdk4
      was predominant in hyperplasias and much less in tumors, where cyclin D1 became
      predominant. However, the cyclin D2 pool showed increases of 15-65 times in
      hyperplasias compared with normal gland and further increases of 11-15 times in
      two of three different tumors. The message level for cyclin D1 increased only 2-3
      times in tumors compared with normal gland. Cyclin D2 mRNA was highest in normal
      tissue and decreased only marginally in tumors. These results suggest that cyclin
      D2 functions uniquely from cyclin D1 in the early stages of mouse mammary tumor
      development. Cyclin D2 bound to cdk4 may act to guarantee a low level of kinase
      activity in hyperplasias and may be an attempt to direct the mammary epithelial
      cells through differentiation rather than proliferation. This interaction may be
      one of the negative regulatory mechanisms in the early stages in mouse mammary
      tumor development, until cyclin D1 totally replaces cyclin D2 binding to cdk4,
      which would activate the high levels of cdk4 kinase activity observed in
      neoplasias.

PMID- 7586165
TI  - Inhibitory effect of probucol on nephrotoxicity induced by ferric
      nitrilotriacetate (Fe-NTA) in rats.
AB  - Effects of dietary probucol on renal damage induced by a renal carcinogen, ferric
      nitrilotriacetate (Fe-NTA), in male Wistar rats were quantitatively investigated
      with a computer-mediated image analyzer. The kidneys of rats fed a 1% probucol
      diet were protected from necrosis and lipid peroxidation induced by a single i.p.
      treatment with Fe-NTA solution at 5 mg Fe/kg body wt and were significantly
      resistant to a higher dose. For the parameter of lipid peroxidation, Schiff's
      staining method was utilized to demonstrate the extent of formation of aldehydes,
      products of lipid peroxidation. Thus following injection of Fe-NTA solution at 10
      mg Fe/kg body wt the average areas of tubular necrosis were 85.8% versus 56.9%
      and the positive areas for Schiff's staining were 15.3% versus 5.6% in the renal
      cortices of rats fed control of 1% probucol diets respectively. These results
      indicate that probucol provides protection against Fe-NTA-induced nephrotoxicity
      through its antioxidant properties. In addition to being a cholesterol-lowering
      drug, useful for the control of hypercholesterolemia, probucol may therefore be
      beneficial for prevention and treatment of various pathogenic processes including
      those leading to carcinogenesis.

PMID- 7586162
TI  - N-(4-hydroxyphenyl)retinamide: interactions with retinoid-binding
      proteins/receptors.
AB  - The cellular transport, metabolism and biological activity of retinoids are
      mediated by their specific binding proteins and nuclear receptors. For an
      understanding of the mode of action of retinoids with potential cancer
      chemopreventive or other biological activity, it is important to study their
      interactions with these binding proteins and receptors. In our attempts to
      understand the action of N-(4-hydroxyphenyl)retinamide (4HPR) and other
      retinamides in the prevention of cancer, we observed that 4HPR binds to a serum
      protein with a molecular size of approximately 20,000. The retinoid, however, did
      not show any binding affinity for cellular retinol-binding protein (CRABP) or for
      cellular retinoic acid-binding protein (CRABP). However, it showed binding
      affinity for the nuclear receptors of retinoic acid (RARs) equivalent to 15% of
      that of retinoic acid. The physicochemical properties of the 4HPR binding protein
      in the serum were identical to those of serum retinol binding protein (RBP).
      Antibodies against RBP quantitatively immunoprecipitated the protein-4HPR
      complex, confirming that the retinoid specifically binds to RBP. Although retinol
      and 4HPR cross-competed for RBP binding, N-phenylretinamide, in which the 4
      hydroxyl group is absent, and N-(4-methoxyphenyl)retinamide, a major cellular
      metabolite of 4HPR, in which the hydroxyl group is blocked, did not show affinity
      for the binding protein. The results indicate that the hydroxyl group of 4HPR is
      essential for binding of this type of retinoid to RBP. Thus, our studies suggest
      that serum transport of 4HPR may be facilitated by RBP. To bind more efficiently
      to CRBP, CRABP, or RARs/RXRs, the retinoid may require further metabolic change.

PMID- 7586163
TI  - Mutation spectrum of cigarette smoke condensate in Salmonella: comparison to
      mutations in smoking-associated tumors.
AB  - We used colony probe hybridization and polymerase chain reaction/DNA sequence
      analysis to determine the mutations in approximately 1600 revertants of
      Salmonella induced by cigarette smoke condensate (CSC) in the presence of S9. CSC
      induced approximately 80% GC-->TA transversions and approximately 20% GC-->AT
      transitions at the base-substitution allele (hisG46) in strain TA100. This
      spectrum was similar to those of the polycyclic aromatic hydrocarbon (PAH)
      benzo[alpha]pyrene and various aromatic amines such as 4-aminobiphenyl and Glu-P
      1, all of which are present in CSC. This spectrum was also similar to that
      produced by PAHs in other bacteria, mammalian cells, and rodents as well as to
      that of the p53 gene in lung tumors from smokers. The results in Salmonella are
      consistent with a role for the PAH component of cigarette smoke in the base
      substitution specificity found in the p53 gene of smoking-associated lung tumors.
      At the frameshift allele in strains TA1538 and TA98, CSC induced only a hotspot 2
      base deletion, which is a mutation spectrum that is identical to that induced by
      the heterocyclic amine pyrolysate products of amino acids, such as Glu-P-1. This
      is consistent with bioassay-directed fractionation studies showing that aromatic
      amines account for most of the frameshift specificity of CSC in Salmonella.
      Rodent and human studies indicate that aromatic amines are responsible for
      smoking-associated bladder cancer. Repeated freezing and thawing of the CSC
      samples changed the chemical composition of the mixtures as evidenced by the
      production of an altered mutation spectrum. This emphasizes the necessity of
      proper storage and handling of labile complex mixtures. This study (i) confirms
      our previous studies showing that the mutation spectrum of a complex mixture
      reflects the dominance of one or a few classes of chemical mutagens within the
      mixture, and (ii) illustrates the potential of bioassay-directed molecular
      analysis for identifying the chemical classes in a complex mixture that are
      responsible for specific classes of mutation and tumor types produced by the
      mixture.

PMID- 7586164
TI  - The presence of a trifluoromethyl rather than a methyl substituent in the bay
      region greatly decreases the DNA-binding and tumour-initiating activity of the
      cyclopenta[alpha]phenanthren-17-ones.
AB  - The increase in carcinogenicity of polycyclic aromatic compounds following bay
      region methyl group substitution involves a steric component: increasing the size
      of the alkyl substituent decreases the carcinogenic activity of the compound. To
      determine whether there is also an electronic component to this effect, we
      synthesized a bay-region 11-trifluoromethyl analogue of 15,16
      dihydrocyclopenta[alpha]phenanthren-17-one which is sterically similar but
      electronically very different from the 11-methyl derivative. This trifluoromethyl
      derivative bound to DNA in cultures of the human mammary carcinoma cell line MCF
      7 to a much lower extent than the methyl-substituted compound. The
      trifluoromethyl derivative did not form detectable levels of DNA adducts in the
      epidermis of Sencar mice and was inactive as an initiator after promotion with 12
      O-tetradecanoylphorbol-13-acetate for 20 weeks. In contrast, the 11-methyl
      derivative formed > 3 pmol adducts/mg DNA and initiated eight papillomas per
      mouse. These data indicate that both the steric configuration and the electronic
      nature of a bay-region substituent are important in determining the overall
      effect of the substituent on the biological activity of the molecule.

PMID- 7586166
TI  - Influence of amino acids on the formation of mutagenic/carcinogenic heterocyclic
      amines in a model system.
AB  - Mixtures of creatinine, glucose and various single amino acids were heated at 180
      degrees C for 10 min in an aqueous model system. The heated mixtures all showed
      mutagenic activity, ranging from 80 to 2400 TA98 revertant colonies/mumol
      creatinine with metabolic activation. Testing of HPLC fractions for mutagenic
      activity showed each mixture to contain several mutagenic components, some of
      which corresponded to known heterocyclic amines and others to unknown compounds.
      The presence of 2-amino-3-methyl-imidazo[4,5-f]quinoxaline, 2-amino-3,8
      dimethylmidazo[4,5-f]quinoxaline and 2-amino-3,7,8-trimethylimidazo[4,5
      f]quinoxaline in most of the samples was established using HPLC with photodiode
      array detection and liquid chromatography/mass spectrometry with electrospray
      interface and single ion monitoring. In addition, 2-amino-3,4,8
      trimethylimidazo[4,5-f]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5
      f]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 3-amino-1,4
      dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole and
      the co-mutagenic compounds 9H-pyrido[3,4-b]indole and 1-methyl-9H-pyrido[3,4
      b]indole were detected in some samples.

PMID- 7586167
TI  - Formation and persistence of benzo[a]pyrene-DNA adducts in mouse epidermis in
      vivo: importance of adduct conformation.
AB  - The formation and repair of benzo[a]pyrene diol epoxide-N2-deoxyguanosine adducts
      (BPDE-N2-dG) in DNA isolated from the skin of mice treated topically with
      benzo[a]pyrene (BP) was studied by 32P-postlabeling and by low-temperature
      fluorescence spectroscopy under low resolution and under high resolution
      fluorescence line narrowing (FLN) conditions. In agreement with earlier studies,
      total BP-DNA binding reached a maximum at 24 h after treatment (dose: 1
      mumol/mouse), then declined rapidly until 4 days after treatment and much more
      slowly thereafter. An HPLC method was developed which resolved the 32P
      postlabeled (-)-trans- from (-)-cis-anti-BPDE-N2-dG, and (+)-trans-from (+)-cis
      anti-BPDE-N2-dG. High performance liquid chromatography analysis of the major TLC
      adduct spot (containing > 80% of the total adducts) obtained by postlabeling BP
      modified mouse skin DNA showed that it consisted of a major component that
      coeluted with (-)-cis-/(+)-trans-anti-BPDE-N2-dG and a minor component that
      coeluted with (-)-trans-/(+)-cis-anti-BPDE-N2-dG and that the minor component was
      repaired at a slower rate than the major component. Low-temperature fluorescence
      spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE
      N2-dG and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N2-dG.
      In agreement with the 32P-postlabeling results it was observed by fluorescence
      spectroscopy that the (+)-cis-adducts were repaired more slowly than most other
      adducts. Moreover, the (+)-trans-adducts exhibited a broad distribution of base
      stacked, partially base-stacked and helix-external conformations. Mouse skin DNA
      samples obtained at early timepoints (2-8 h) after treatment with BP contained
      substantially more of the 'external' adducts, while samples at later timepoints
      (24-48 h) contained relatively more adducts in the base-stacked conformation,
      indicating also that the latter adducts are repaired less readily than the
      former. The possible biological significance of these novel observations of
      conformation-dependent rates of DNA adduct repair and their possible dependence
      on DNA sequence, are discussed.

PMID- 7586168
TI  - Microsome-mediated 8-hydroxylation of guanine bases of DNA by steroid estrogens:
      correlation of DNA damage by free radicals with metabolic activation to quinones.
AB  - Free radical generation by metabolic redox cycling between catechol estrogens and
      their quinones and subsequent hydroxyl radical damage to DNA have been proposed
      to mediate estrogen-induced renal carcinogenesis in the hamster. In this study
      the content of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker product of
      hydroxyl radical action, was examined in DNA incubated with a liver microsomal
      activating system and with catechol estrogens, equilenin-3,4-quinone or with
      parent estrogens. Equilenin-3,4-quinone increased the formation of 8-OHdG by 50%
      over control levels. 4-Hydroxyestrone and 4-hydroxy-estradiol raised 8-OHdG
      contents significantly, to 1.61 +/- 0.79 and 1.27 +/- 0.31 8-OHdG/10(5)
      deoxyguanosine (dG) respectively over controls (0.68 +/- 0.25 8-OHdG/10(5) dG).
      The corresponding 2-hydroxylated estrogens and the parent hormones estrone,
      estradiol and equilenin did not affect 8-hydroxylation of guanine bases of DNA.
      In incubations of catechol estrogens with microsomes and cumene hydroperoxide the
      4-hydroxyestrogens were oxidized to quinones more rapidly than the 2
      hydroxyestrogens. Our data support a mechanism of hydroxyl radical generation
      from estrogens by redox cycling between 4-hydroxylated metabolites and their
      quinones. The rapid oxidation of 4-hydroxylated estrogens to quinones, their
      redox cycling and hydroxyl radical damage to DNA is consistent with the
      previously reported carcinogenic activities of 4-hydroxylated, but not of 2
      hydroxylated, catechol estrogens.

PMID- 7586169
TI  - Down-regulation by butylated hydroxytoluene of the number and function of gap
      junctions in epithelial cell lines derived from mouse lung and rat liver.
AB  - The mouse pneumotoxicant and lung and liver tumor promoter butylated
      hydroxytoluene (BHT) was examined for its effects on gap junctional intercellular
      communication (GJIC) in mouse lung epithelial (C10) and rat liver epithelial (WB
      F344) cell lines. GJIC, as measured by fluorescent dye microinjection, was
      inhibited in both types of cells by BHT in dose- and time-dependent fashions.
      Inhibition was detected in WB-F344 cells at BHT concentrations > or = 62.5 microM
      and in C10 cells at concentrations > or = 150 microM after 4 h treatment.
      Inhibition occurred within 15-30 min and was reversed by removing BHT from the
      culture medium. The highly toxic BHT metabolite 6-t-butyl-2-(hydroxy-t-butyl)-4
      methylphenol (BHTOH) and the non-toxic BHT metabolite, 2,6-di-t-butyl-4
      hydroxymethylphenol (BHTBzOH) were also tested. In both cell lines BHTOH was a
      more potent inhibitor of GJIC than BHT, whereas BHTBzOH was ineffective. The
      mechanisms of inhibition of GJIC by BHT were also examined. The initial rapid
      inhibition detected within 15-30 min may have been due to gap junction channel
      closure or blockage, since no changes in gap junction number, connexin (Cx) 43
      levels or Cx43 phosphorylation were observed. By 2-4 h, however, gap junctions
      were internalized into the cytoplasm, the number of immunodetectable plasma
      membrane gap junctions was reduced and phosphorylated Cx43-P2 was decreased.
      Treatment of the cells for 24 h with 12-O-tetradecanoylphorbol-13-acetate (TPA)
      prevented inhibition of GJIC by TPA, but not by BHT. Western blot analyses of TPA
      treated WB-F344 or C10 cells revealed the presence of a hyperphosphorylated form
      of Cx43 (Cx43-P3) and no reduction in Cx43-P2, in contrast to BHT-treated cells.
      These data suggest that BHT and TPA inhibit lung and liver epithelial cell GJIC
      through distinct mechanisms.

PMID- 7586170
TI  - Albumin adducts, hemoglobin adducts and urinary metabolites in workers exposed to
      4,4'-methylenediphenyl diisocyanate.
AB  - 4,4'-Methylenediphenyl diisocyanate (MDI) is the most widely used isocyanate in
      the manufacture of polyurethanes. MDI has been implicated as one of the major
      causes of occupational asthma. Hydrolysis of MDI can yield 4,4'
      methylenedianiline (MDA), which is a suspected human carcinogen. Thus the need to
      monitor occupational exposure to MDI is of great significance. The use of air
      monitors alone has been found to be insufficient and there is a need for
      sensitive markers of recent and long-term exposure. We obtained biological
      samples from a group of 20 workers exposed to MDI vapor during the manufacture of
      polyurethane products. The air levels of MDI in the factory were measured using
      personal, work room and work station monitors. In most cases the levels were
      below detection limits. The blood and urine samples were analyzed for the
      presence of adducts and metabolites using GC-MS methods. Urinary base-extractable
      metabolites were found above control levels in 15 of the 20 workers and ranged
      from 0.035 to 0.83 pmol MDA/ml. The level of the acetylated metabolite N'-acetyl
      4,4'-methylenedianiline (AcMDA) ranged from 0.13 to 7.61 pmol/ml. The amount of
      MDA released after acid hydrolysis was on average 6.5 times higher than the
      amount of free MDA and AcMDA present in urine. MDA was detected as a hemoglobin
      (Hb) adduct in all of the 20 subjects. The level ranged from 70 to 710 fmol/g Hb.
      In one individual the Hb adduct of AcMDA was detected. This is the first time a
      Hb adduct of AcMDA has been detected after occupational exposure to MDI. This is
      a further piece of evidence for the biological availability of the suspected
      human carcinogen MDA from in vivo hydrolysis of MDI. Plasma albumin conjugates of
      MDI can cause the onset of respiratory disorders in both man and animal models.
      Thus we investigated the presence of plasma protein adducts. The plasma MDA
      levels ranged from 0.25 to 5.4 pmol/ml. Up to 120 fmol/mg were found to be
      covalently bound to albumin.

PMID- 7586171
TI  - Spectroscopic characterization of specific phorbol ester binding to PKC-receptor
      sites in membranes in situ.
AB  - Electron paramagnetic resonance (EPR) spectra were measured for the spin labelled
      phorbol-12,13-diester [5,6]PA bound to membranes of the particulate fraction of
      mouse brain tissue rich in PKC receptors. [5,6]PA is a bioactive derivative of
      the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), carrying
      the spin label in a doxyl group in position 7' of the 12-O-tetradecanoyl residue.
      A mathematical model based on special algorithms (Griffith, O.H. and Jost, P.C.
      Spin labeling: theory and applications, 1976) allows a satisfactory
      reconstruction of the experimental spectrum. It reveals that in the experimental
      spectrum the signal from the [5,6]PA molecules bound non-specifically to the
      lipid bilayer of the membranes is superimposed by the signal of [5,6]PA molecules
      bound specifically, i.e. to the active site of PKC (approximately 10% of total
      EPR signal intensity). Moreover, interpretation of spectral parameters indicates
      that in [5,6]PA molecules bound specifically the tetradecanoyl chain exhibits a
      larger motional freedom compared to that in [5,6]PA bound non-specifically. These
      new findings are in accordance with views featured independently by two recent
      molecular models of interaction of PKC with cellular membranes (8,9).

PMID- 7586173
TI  - Inhibitory effect of probucol on benzo[a]pyrene induced lung tumorigenesis.
AB  - The effects of probucol, a clinically used cholesterol lowering and antioxidant
      drug, on benzo[a]pyrene (B[a]P) induced pulmonary and forestomach tumorigenesis
      as well as induction of colonic aberrant crypt foci (ACF) in female A/J mice was
      investigated. Diet containing 1% probucol fed prior to, during and after 8 bi
      weekly 1 mg/mouse oral intubations of B[a]P, reduced the number of pulmonary
      adenomas by 52% (P < 0.001) and the number of forestomach tumors by 31%. The
      0.06% probucol diet also resulted in decreased tumor formation but the
      differences did not reach statistical significance. Both probucol diets
      significantly reduced the numbers of large ACF, putative preneoplastic lesions of
      the colon mucosa, but showed no effects on the total numbers of ACF. The results
      of this study suggest that probucol may also be useful as a chemopreventive
      agent, in addition to being a cholesterol lowering and anti-atherogenic drug with
      low toxicity.

PMID- 7586172
TI  - Gender-specific and developmental differences in protein kinase C isozyme
      expression in rat liver.
AB  - Protein kinase C (PKC) activity is important in regulating cellular growth and
      differentiation and is believed to play a role in the promotional stage of
      carcinogenesis. To determine the effects of age and gender on PKC expression,
      isozyme-specific antibodies and immunoblot analyses were employed to examine the
      expression of PKC alpha, PKC beta, PKC gamma, PKC delta and PKC epsilon in the
      cytosolic and membrane fractions isolated from hepatic tissue of 1, 3, 5 and 12
      week old male or female rats. PKC alpha levels were comparable at 1 week of age
      in the respective male and female hepatic fractions. In contrast, at 3, 5 and 12
      weeks of age, cytosolic PKC alpha levels were approximately 2-, 5- and 7-fold
      greater, respectively, in females than in males. At 5 weeks of age, cytosolic
      levels of PKC delta were approximately 2-fold higher in females than in males.
      Other PKC isozymes were either below the limit of detection (PKC gamma), or
      failed to exhibit any gender-related differences (PKC beta and PKC epsilon). At
      12 weeks of age, PKC activity was 1.7- or 2.4-fold greater in hepatic cytosol and
      membrane fractions, respectively, from females than in male samples. These
      results show distinct gender-specific and developmental differences in hepatic
      PKC isozyme expression, which may play a role in susceptibility to cancer.

PMID- 7586174
TI  - Effects of docosahexaenoic acid (DHA) on intestinal polyp development in Apc
      delta 716 knockout mice.
AB  - Epidemiological studies and animal experiments show an association of dietary
      intake of fish oils and low incidence of several types of cancers. The active
      ingredients of fish oils appear to be polyunsaturated fatty acids of omega-3 type
      such as eicosapentaenoic acid and docosahexaenoic acid (DHA). We have
      investigated chemopreventive effects of DHA on mouse intestinal polyposis using
      adenomatous polyposis coli (Apc) gene knockout mice. Damage to the human APC gene
      is responsible for not only familial adenomatous polyposis but also many sporadic
      cancers of the entire digestive tract. Using homologous recombination in
      embryonic stem cells, we recently constructed gene knockout mice containing a
      truncation mutation in the Apc gene at codon 716 (Apc delta 716). The
      heterozygous mice developed numerous intestinal polyps, and all microadenomas
      dissected from the earliest polyps had already lost the wild-type allele,
      indicating the loss of heterozygosity [Oshima et al. (1995), Proc. Natl Acad.
      Sci. USA, 92, 4482-4486]. We fed Apc delta 716 heterozygotes with AIN-76A
      purified diet containing 3% DHA for 7 weeks, and scored the number and size of
      intestinal polyps. Average DHA intakes per day were 4.1 and 4.3 g/kg body wt for
      males and females, respectively. DHA-fed females had only 31% of polyps compared
      with the control females that developed about 220 polyps, whereas DHA-fed females
      showed no significant decrease in the polyp number. As for the polyp size, the
      proportion of larger polyps decreased more significantly in females than in
      males. This is the first demonstration that DHA inhibits intestinal polyposis
      induced by an Apc mutation at both its formation and growth.

PMID- 7586176
TI  - Hepatocarcinogenicity of chlordane in B6C3F1 and B6D2F1 male mice: evidence for
      regression in B6C3F1 mice and carcinogenesis independent of ras proto-oncogene
      activation.
AB  - Logistic regression analysis of age-specific prevalences for neoplastic and non
      neoplastic liver lesions was used to examine treatment responses for B6C3F1 and
      B6D2F1 male mice continuously exposed to chlordane (55 p.p.m.) and to determine
      whether neoplasms were dependent on continuous exposure in the B6C3F1 mice. In
      order to determine if ras oncogene activation plays a role in the carcinogenicity
      of chlordane and whether the activation is dependent on genetic background, liver
      tumors from chlordane-treated B6C3F1 and B6D2F1 mice were analyzed for the
      presence of activating mutations in the ras oncogene. The overall liver tumor
      prevalence at terminal killing was nearly 100% for both strains; however, the age
      specific prevalence increased more rapidly in B6C3F1 mice than in B6D2F1 mice.
      Tumor-bearing B6C3F1 mice had an average of two or more tumors per liver than
      B6D2F1 mice at their respective terminal killings (5.4 versus 3.3). When
      chlordane exposure was discontinued for a group of B6C3F1 mice ('stop' group) at
      491 days of age, overall tumor multiplicity significantly decreased by 30% from
      an average of 4.4 per tumor-bearing-animal at 525 days to 3.1 at terminal killing
      (568 days). Over the same time period the prevalence of hepatocellular carcinomas
      significantly decreased from 80 to 54% and adenomas from 100 to 93% by terminal
      killing in B6C3F1 'stop-group' mice. Chlordane induced diffuse hepatocellular
      centrilobular hypertrophy, frequent multinucleate hepatocytes, toxic change and
      hepatoproliferative lesions composed predominantly of acidophilic hepatocytes in
      nearly 100% of both the B6C3F1 and B6D2F1 mice. The development of histological
      evidence of toxicity closely paralleled the temporal development of
      hepatocellular neoplasia and decreased in severity when the tumor burden was
      maximal. No H- or K-ras mutations were detected in the chlordane-induced
      hepatocellular tumors in B6C3F1 mice (15 adenomas and 15 carcinomas) or B6D2F1
      mice (10 adenomas and 10 carcinomas). In conclusion, chlordane induced liver
      tumors in both B6C3F1 and B6D2F1 male mice by mechanisms independent of ras
      oncogene activation and 30% of both benign and malignant liver tumors in the
      B6C3F1 mice regressed after exposure was discontinued.

PMID- 7586175
TI  - Formation and persistence of DNA adducts in organs of CD-1 mice treated with a
      tumorigenic dose of fluoranthene.
AB  - Fluoranthene (FA) is tumorigenic to the lung when injected i.p. into CD-1 mice 1,
      8 and 15 days after birth (Wang, J.-S. and Busby, W.F. Jr, Carcinogenesis, 14,
      1871-1874, 1993). Levels, tissue distribution and persistence of FA--DNA adducts
      detected by HPLC-32P-postlabeling were investigated during the course of lung
      tumorigenesis by FA. Anti-10b-N2-deoxyguanosin-1,2,3,-trihydroxy-1,2,3 10b
      tetrahydrofluoranthene [sequence: see text] (anti-FADE adduct) was consistently
      the major adduct in DNA samples from lung, heart, liver and kidney of animals
      examined at different time points from 2 h to 165 days after the last treatment
      with the tumorigenic dose (3.5 mg/mouse) of FA. Several unidentified adducts were
      also detected. Lung, the target organ for FA tumorigenicity, contained higher
      levels of anti-FADE adduct than other tissues from 1-165 days after treatment.
      The anti-FADE adduct level decreased in a biphasic manner after reaching maximum
      values at 2 h in heart and spleen plus thymus and 3 days in lungs, liver and
      kidneys. About 10% of the maximum amount of anti-FADE adduct remained in lung,
      liver and heart 165 days after final FA treatment, at which time 44% of animals
      had developed lung adenomas. Significant inter-litter variations, but no sex
      differences in adduct levels were observed. These results indicated a positive
      correlation between anti-FADE adduct level and persistence in relation to target
      organ specificity for tumor formation.

PMID- 7586178
TI  - Initiation of hepatocarcinogenesis by endogenously formed N-nitrosobis(2
      hydroxypropyl)amine, N-nitrosodiethanolamine and N-nitroso-2,6-dimethylmorpholine
      in rats.
AB  - Initiation activities of endogenously formed N-nitrosobis(2-hydroxypropyl)amine
      (NBHPA), N-nitrosodiethanolamine (NDELA) and N-nitroso-2,6-dimethylmorpholine
      (NDMM) were investigated in a modified short-term assay for rat
      hepatocarcinogenesis. Male Wistar rats were fed 1% bis(2-hydroxypropyl)amine,
      0.5% diethanolamine or 0.25% 2,6-dimethylmorpholine in the diet plus 0.3% sodium
      nitrite in the drinking water. Two weeks after starting the experimental regimen
      they underwent 2/3 partial hepatectomy and were then maintained on the respective
      diets for a further week. Following a 2 week recovery period on basal diet rats
      were subjected to a resistant hepatocyte regimen consisting of 0.02% 2
      acetylaminofluorene in the diet for 2 weeks and 1 mg carbon tetrachloride/kg body
      wt by gavage at the midpoint. Initiation activity was assayed by measuring
      hepatic foci positive for gamma-glutamyltranspeptidase. Numbers of such foci per
      cm2 were significantly increased in the groups given the secondary amines
      together with nitrite compared with values for groups given each precursor or
      nitrite alone. Further, the numbers of lesions were essentially similar to those
      found in rats given carcinogenic doses of NBHPA, NDELA and NDMM. The results
      clearly of demonstrate hepatocyte initiation activities of endogenously formed
      carcinogens, presumably NBHPA, NDELA and NDMM.

PMID- 7586179
TI  - Urinary excretion of 3-methyladenine and 3-ethyladenine after controlled exposure
      to tobacco smoke.
AB  - The urinary excretion of the DNA alkylation products 3-methyladenine (3-MeAde)
      and 3-ethyladenine (3-EtAde) after controlled exposure to cigarette smoke over a
      period of 4 days was determined by competitive radioimmunoassay after separation
      by HPLC. Twenty-four hour urine samples were collected from five smokers and five
      non-smokers. Days 1 and 3 (control days) were without smoking, on days 2 and 4
      smokers consumed 24 cigarettes each within 8 h in an unventilated room (45 m3) in
      the presence of non-smokers. Average levels of carbon monoxide during exposure
      were 15-20 p.p.m., 2.8-3.5 mg/m3 of respirable suspended particles and 75-86
      micrograms/m3 of nicotine. Carboxyhemoglobin levels increased by 9.0 and 1.8% in
      smokers and passive smokers respectively. On control days, urinary excretion of 3
      MeAde was similar in smokers and non-smokers (4.7-6.2 micrograms/24 h). Smoking
      resulted in a significant increase (P < 0.01) in 3-MeAde excretion (13.6-14.8
      micrograms/24 h); no change was observed in the average excretion of 3-MeAde by
      passive smokers (4.8-4.9 micrograms of 3-MeAde/24h). Baseline 3-EtAde excretion
      on control days was similar in smokers and passive smokers (13.7-32.8 ng/24 h).
      In smokers, the amount of urinary 3-EtAde was increased > 5-fold (119.3-138.5
      ng/24 h) on smoking days; no effect on 3-EtAde excretion was observed on average
      in passive smokers (18.0-25.2 ng/24 h). The nature of the DNA-reactive agent(s)
      responsible for the increased urinary excretion of 3-alkyladenines, in particular
      of the sensitive indicator 3-EtAde, remains to be determined.

PMID- 7586180
TI  - Evidence from 32P-postlabeling and the use of pentachlorophenol for a novel
      metabolic activation pathway of diethylstilbestrol and its dimethyl ether in
      mouse live: likely alpha-hydroxylation of ethyl group(s) followed by sulfate
      conjugation.
AB  - Diethylstilbestrol (DES), a synthetic stilbene estrogen, is a potent development
      toxin and carcinogen in humans and rodents. A number of 32P-postlabeling studies
      suggest that genotoxic effects of DES substantially contribute to these
      biological effects. The mechanisms involved in DES-mediated genotoxicity are not
      completely understood, however. As reported here, the structural resemblance of
      tamoxifen to DES led to the hypothesis that DES may be hydroxylated and sulfated
      at the allylic C2 and/or C5 of the ethyl side chains in analogy to alpha
      hydroxylation and sulfation of and DNA adduct formation by tamoxifen. Female ICR
      mice were administered 500 mumol/kg DES or its dimethyl ether derivative
      (DiMeDES), either alone or in combination with the sulfotransferase inhibitor
      pentachlorophenol (PCP) (75 mumol/kg), once daily for 4 days. Liver DNA adducts
      were measured 24 h after the last dose by dinucleotide/monophosphate 32P
      postlabeling. Administration of DES or DiMeDES led to the formation of a unique
      and novel pattern of several major DNA adducts which were absent in vehicle
      controls. With minor exceptions the pattern was qualitatively similar for the two
      compounds, suggesting rapid O-demethylation of DiMeDES to DES in vivo followed by
      metabolic activation. Adducts formed in vivo did not chromatographically match
      DES quinone adducts synthesized in vitro. Co-administration of PCP with DES or
      DiMeDES significantly decreased adduct formation from either compound, by 33-61%.
      Taken together, these results are consistent with a hitherto unrecognized pathway
      of metabolic activation and DNA adduct formation by DES involving the putative
      hydroxylation of the allylic alpha-carbon of the ethyl side chain(s), followed by
      formation of DNA-reactive sulfuric acid esters. DES is now known to induce DNA
      damage in vivo by at least four different mechanisms. It is postulated that this
      multiplicity of mechanisms in itself explains why this drug elicits such a
      plethora of unique and complex pathophysiological effects in adults and off
      spring of different species.

PMID- 7586181
TI  - Efficacy of cancer prevention by high-selenium garlic is primarily dependent on
      the action of selenium.
AB  - We reported previously that garlic cultivated with selenite fertilization showed
      powerful chemopreventive activity in the rat dimethylbenz[a]anthracene (DMBA)
      induced mammary tumor model (Carcinogenesis 15, 573-576, 1994). In order to
      ascertain that the efficacy of the high-selenium garlic in cancer protection is
      primarily dependent on the action of selenium we compared the effects of two
      batches of garlic powder with marked differences in their level of selenium
      enrichment, 112 or 1355 p.p.m. Se dry weight. Both products were added to the
      diet to achieve the same final concentration of 2 p.p.m. Se. The supplementation
      protocol was designed to evaluate the efficacy during either the initiation phase
      or post-initiation phase of DMBA mammary carcinogenesis. Significant tumor
      reduction was observed with either treatment protocol. Furthermore, the magnitude
      tumor suppression, as well as the extent of DMBA-DNA adduct inhibition, were very
      similar with the two batches of garlic, even though the amounts of garlic in the
      diet varied considerably between them (1.8% for the 112 p.p.m. Se garlic versus
      0.15% for the 1355 p.p.m. Se garlic). This suggests that the anti-cancer activity
      of the high-selenium garlic was likely to be accounted for by the effect of
      selenium, rather than the effect of garlic per se. A continuous feeding of the
      high-selenium garlic produced a modest increase in total selenium in various
      tissues. In general the profile of selenium accumulation was comparable in rats
      ingesting either the 112 or the 1355 p.p.m. Se garlic. Thus, based on the results
      of several biological responses, it appears that the ability of the high-selenium
      garlic to protect against tumorigenesis is primarily dependent on increased
      intake of selenium provided by the vegetable. Future research will be focused on
      the chemical form of selenium in the garlic.

PMID- 7586183
TI  - Mutational and LOH analyses of p53 alleles in colon tumors induced by 1,2
      dimethylhydrazine in F1 hybrid mice.
AB  - To elucidate the role of p53 in colon tumorigenesis in mice, we examined allele
      loss and mutational alteration of the p53 gene in colon tumors induced by 1,2
      dimethylhydrazine (DMH) in F1 hybrid mice. Intragenic polymorphism of the p53
      gene among parental strains enabled us to assess allele loss of the p53 gene and
      also to determine parental origin of mutated and/or lost alleles. Allele loss was
      detected in two of 163 tumors heterozygous for the p53 gene. Polymerase chain
      reaction-single-strand conformation polymorphism analysis of p53 exons 5-8
      revealed 33 mutations in 20 of 182 colon tumors, the incidence being lower than
      that in human colon cancers. The majority of these mutations were of transition
      type: G:A transitions at non-CpG sites were most prevalent, while those at CpG
      sites were less common. Distribution of the mutations along p53 amino acid
      sequence revealed a difference in the location of 'hot spots' between mice and
      humans. Incidence of p53 alterations did not differ among alleles of different
      parental origins, suggesting that genetic changes in DMH-induced mouse colon
      tumors had occurred independently of parental origin and DMH susceptibility.
      Detailed analysis of p53 mutations on each allele revealed intratumoral
      heterogeneity in mouse colon tumors. The low incidence of p53 mutations and rare
      allele loss suggest that p53 alteration plays only a minor role in colon
      tumorigenesis in mice.

PMID- 7586184
TI  - Separation of transforming amino acid-substituting mutations in codons 12, 13 and
      61 the N-ras gene by constant denaturant capillary electrophoresis (CDCE).
AB  - We used high fidelity PCR and constant denaturant capillary electrophoresis
      (CDCE) [Khrapko et al. (1994) Nucleic Acids Res., 22, 364-369] to separate wild
      type and different mutant N-ras exon 1 and 2 sequences. The set of plasmids
      containing N-ras cDNA, wild type or mutant sequences representing all
      transforming amino acid-substituting single base pair changes in codons 12, 13
      (exon 1) and 61 (exon 2), were amplified using Pfu polymerase in a limited cycle
      polymerase chain reaction. One of the primers used for the amplification of each
      exon included a 40 nucleotide GC rich sequence that created high and low melting
      domains. The amplified fragments 151 bp (exon 1) and 150 bp (exon 2) were run on
      the CDCE with the 'denaturant zone' temperature of the capillary corresponding to
      the melting temperature of 111 bp (exon 1) and 110 bp (exon 2) low melting
      domains. The separation was achieved between wild type and mutant sequences as
      homoduplexes in 15 out of 19 cases, as a single base substitution alters the
      electrophoretic mobility of a partially melted double stranded fragment. The
      denaturation and reannealing of wild type and mutant fragments together created
      wild type/mutant heteroduplexes. All the heteroduplexes were well resolved from
      wild type homoduplex. In the current form mutant sequences were detected at a
      frequency of 10(-3) in the presence of wild type. This study has resulted in
      obtaining electrophoretic spectrum of different N-ras mutants on CDCE as
      homoduplexes as well as heteroduplexes.

PMID- 7586185
TI  - Human CYP2D6 gene polymorphism in Slovene cancer patients and healthy controls.
AB  - The polymorphic CYP2D6 gene encoding debrisoquine hydroxylase has attracted much
      interest for its possible role in human pulmonary carcinogenesis. The purpose of
      this work was to determine the frequency of poor metabolizers (PM) and extensive
      metabolizers (EM) of debrisoquine in Slovene population of healthy individuals (n
      = 107), lung cancer patients (200) and melanoma patients (121). Polymorphism of
      CYP2D6 gene was studied by genotyping based on PCR analysis of the intron 3 exon
      4 junction containing G to A mutation and one base pair deletion in exon 5, which
      are responsible for approximately 95% of poor metabolizer phenotype in
      Caucasians. In the healthy Slovene population 62.5% of individuals were
      identified as extensive metabolizers, 31% as extensive-heterozygous metabolizers
      and 6.5% as poor metabolizers of debrisoquine. The frequency of EM individuals
      was 70.5% in lung cancer patients and 64% in melanoma patients, the frequency of
      extensive-heterozygous subjects was 27% in lung cancer patients and 31% in
      melanoma patients. The frequency of PM individuals in the lung cancer patients
      was 2.5% and in melanoma patients 5%. The decrease in PM genotype in the group of
      Slovene lung cancer patients is similar to the decrease published for some other
      ethnic groups. Our results support the hypothesis that polymorphic CYP2D6 gene
      probably plays some, though not a prevalent role in chemical carcinogenesis. Poor
      metabolizer individuals appear to be less susceptible to lung cancer than EM
      individuals.

PMID- 7586182
TI  - Marked increase in urinary excretion of nitrate and N-nitrosothioproline in the
      osteogenic disordered syndrome rats, lacking ascorbic acid biosynthesis, by
      administration of lipopolysaccharide and thioproline.
AB  - Urinary excretions of nitrate and N-nitrosothiazolidine-4-carboxylic acid (N
      nitrosothioproline; NTPRO) were determined in rats with osteogenic disordered
      syndrome (ODS, od/od), lacking L-ascorbic acid (ASC) biosynthesis, after i.p.
      administration of Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) followed by
      thiazolidine-4-carboxylic acid (thioproline, 20 mg/rat). L-Ascorbic acid
      sufficient ODS rats showed the excretion of nitrate and NTPRO at the levels of
      20.3 +/- 7.9 mumol/24h and 369 +/- 111 pmol/24 h respectively, whereas the levels
      of nitrate and NTPRO in ASC-deficient (scorbutic) rats increased to 54.7 +/- 5.6
      mumol/24 h (P < 0.01) and 796 +/- 367 pmol/24 h (P < 0.05) respectively.
      Administration of L-arginine further increased urinary excretion of nitrate and
      NTPRO while D-arginine showed no effect. NG-Monomethyl-L-arginine, a specific
      inhibitor of nitric oxide synthase (NOS), strongly inhibited endogenous formation
      of both nitrate and NTPRO. These results indicate that increased excretion of
      NTPRO in ODS rats stimulated by LPS involves induction of NOS leading to an
      increase in endogenous formation of reactive nitrogen oxides such as N2O3, a
      potent nitrosating agent at physiological pH conditions. Increased NOS activities
      in the plasma and various tissues of ODS rats were observed 5 h after treatment
      with LPS. The possibility of extragastric N-nitroso compound formation in
      inflammation sites is discussed.

PMID- 7586186
TI  - Hexamethylmelamine is a potent inducer of deletions in male germ cells of
      Drosophila melanogaster.
AB  - Chemotherapy-related second tumors constitute a matter of concern in cancer
      treatment. Therefore, it is of great interest to elucidate the mechanisms by
      which cytostatic drugs exert their mutagenic and/or carcinogenic activity besides
      the anticancer effect and the possible relationship among them. A useful and
      informative approach to this problem is the analysis of the mutation spectra
      induced by these drugs in eukaryotic organisms. Sequence analysis of the
      mutations induced by hexamethylmelamine, a crosslinking agent extensively used in
      the treatment of ovarian cancer, in male germ cells of Drosophila was conducted
      using the v locus as reporter gene. Both intra-locus and multi-locus deletions
      were induced whereas based changes were almost absent. Thus, it is proposed that
      deletions are likely to be involved in the generation of second malignancies in
      hexamethylmelamine-treated patients. It has to be stressed that systems, such as
      v, capable of efficiently recovering mutations caused by big losses of DNA,
      should be used for the study of mutational spectra induced by cross-linking
      agents.

PMID- 7586177
TI  - Assessment of chlorinated pesticide residues in cigarette tobacco based on
      supercritical fluid extraction and GC-ECD.
AB  - It has been established that the organochlorinated compounds (OCC) DDT and DDE
      are xenoestrogens which influence both normal and neoplastic estrogen-responsive
      tissues. Therefore, it has been hypothesized that OCC contribute to the risk for
      breast cancer. Although the food chain has been recognized as a major source of
      human exposure to these compounds, tobacco and tobacco smoke were also considered
      as sources of exposure to OCC. This study was aimed at quantifying OCC in tobacco
      and cigarette smoke and at documenting changes in the concentrations of these
      pesticides in tobacco products since 1970 when OCC were banned for use on
      tobacco. To determine the levels of OCC residues on tobacco, we developed a new
      method based on superficial fluid extraction, followed by clean-up on an alumina
      column, and analysis by gas chromatography with electron capture detection. The
      detection limit for an individual OCC is 1 ng/g tobacco, the relative SD is < 10%
      for each analyte and the new method compares well with the standardized method
      that involves conventional organic solvent extraction. The major OCC determined
      in the tobaccos and in cigarette smoke of US commercial brands that were
      manufactured in the proceeding three decades were p.p'-isomers of DDD (1540-20
      220 ng/g tobacco), DDT (720-13 390 ng) and DDE (58-730 ng). Since 1970, the
      concentrations of individual OCC in tobacco have gradually decreased by > 98%.
      The transfer rate from tobacco into mainstream smoke amounts to 22% for DDD, 19%
      for DDT and 27% for DDE. Today, the concentrations of the OCC in US tobacco are
      below the maximum permissible limits set by the Environmental Protection Agency.
      While until 1970 the OCC in tobacco and tobacco smoke contributed significantly
      to the bioaccumulation of the pesticides in smokers, at this time tobacco and
      cigarette smoke are a minor source of human exposure.

PMID- 7586187
TI  - Inhibition of Western-diet induced hyperproliferation and hyperplasia in mouse
      colon by two sources of calcium.
AB  - A Western-style diet containing high-fat and phosphate, and low calcium and
      vitamin D was fed to mice for 20 weeks. Starting at week 8, subgroups of animals
      received the Western-style diet supplemented by two different calcium sources:
      tricalcium phosphate and calcium citrate malate. Hyperproliferation (increased
      [3H]thymidine-labelled cells/colonic crypt) and hyperplasia (increased total
      epithelial cells/crypt) developed in the sigmoid colon after 8 weeks of feeding
      the Western-style diet confirming previous results, and these were reversed at
      later periods by the addition of the two calcium sources to the Western-style
      diet. Findings indicate that the modified colonic epithelial cell
      hyperproliferation and hyperplasia which have been associated with subsequent
      development of colonic neoplasia, are induced in mice fed a Western-style diet,
      and the addition of calcium to the diet inhibited their development in the
      colonic mucosa.

PMID- 7586188
TI  - Pyrrolizidine alkaloid-induced DNA-protein cross-links.
AB  - Pyrrolizidine alkaloids (PAs) are potent carcinogenic and anti-mitotic compounds
      produced by a large number of plant species. In this study, we investigated in
      vitro the DNA-protein cross-linking activity of several structurally diverse PAs.
      The DNA cross-linked proteins induced by PAs were also isolated and characterized
      in mammalian cells. At 300 and 500 microM, the pyrrolic PAs (dehydrosenecionine,
      dehydromonocrotaline, dehydroseneciphylline, dehydroriddelliine) induced potent
      DNA cross-links. Protein-associated DNA cross-links accounted for approximately
      50% of the total cellular DNA cross-links at 300 microM. The simple necine
      pyrrole dehydroretronecine induced few DNA--protein cross-links and none were
      detected with indicine N-oxide. The major proteins cross-linked to DNA from
      either PA-exposed cells or pyrrolic PA-exposed nuclei were in the molecular
      weight 40-60 kDa range and were primarily acidic in nature (Ca. pI 4.2-5.0). The
      patterns of the proteins cross-linked to DNA were similar to that induced by
      standard bifunctional alkylating agents mitomycin C, cisdichlorodiammine
      platinum(II) and nitrogen mustard. The macrocyclic pyrrole dehydrosenecionine
      induced DNA cross-links in pBR322 plasmid DNA with BSA as a protein target. Our
      data indicated that pyrrolic PAs with a macrocyclic diester such as
      dehydrosenecionine, dehydroseneciphylline, dehydroriddelliine and
      dehydromonocrotaline were more potent cross-linkers than the simple necine
      pyrrolic dehydroretronecine. Cross-linking potency of the PAs examined here
      coincides with known potency differences in animal toxicity and led us to
      conclude that DNA--protein cross-linking activity is probably involved in PA
      related

PMID- 7586189
TI  - The effects of cycloheximide and WR-1065 on radiation-induced repair processes: a
      mechanism for chemoprevention.
AB  - The effects of cycloheximide (CHX) and 2-[(aminopropyl)-amino]ethanethiol (WR
      1065), each alone or in combination, on radiation-induced mutation induction at
      the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus and cell killing
      were investigated using a Chinese hamster ovary (CHO) AA8 cell system. Treatment
      with CHX, a potent inhibitor of protein synthesis, at a concentration of 10
      micrograms/ml administered 30 min prior to irradiation with 7.5 Gy had no effect
      on cell survival but did reduce the radiation-induced mutation frequency (per
      10(6) survivors) from 106.5 +/- 8.8 (SEM) to 36.2 +/- 5.6 (SEM). Exposure of
      cells to 4 mM WR-1065 reduced the mutation frequency to 44.8 +/- 4.2 (SEM), but
      the combination of agents afforded no additional protection, that is 41.1 +/- 3.3
      (SEM). The mechanism of action attributed to CHX in reducing mutation frequency
      is its ability to prevent the induction of an error-prone repair system. Split
      dose radiation experiments, that is 8 Gy versus 4 Gy + 4 Gy separated by 3 h,
      were performed to evaluate and contrast the relative abilities of CHX and WR
      1065, each alone or in combination, in affecting cell survival. Cycloheximide
      administered to cells 30 min before the first radiation dose and present
      throughout the 3 h incubation time prior to the second dose inhibited split-dose
      repair as evidence by a reduction in surviving fraction by 60% as compared with
      the value obtained for non-CHX-treated cells that were exposed to two equal doses
      of 4 Gy. Cells exposed to 4 mM WR-1065 immediately following the first 4 Gy
      radiation dose and then washed free 2.5 h before exposure to a second Gy dose,
      which was also followed by a 30 min exposure to WR-1065, increased the surviving
      fraction by 80% over the value obtained for cells not exposed to WR-1065 during
      their split-dose radiation treatment. When CHX treatment was combined with WR
      1065 was abolished, that is surviving cell fraction was again reduced by
      approximately 60% as compared with untreated control groups. These results
      indicate that protein synthesis is required for WR-1065 to affect split-dose
      related repair processes. Presumably, the inhibition of the induction of an error
      phone repair system by CHX would account for its effects on both resultant
      decreases in mutation frequency and cell survival. In contrast, WR-1065 and/or
      its disulfide metabolite appear to facilitate the efficacy and fidelity of such a
      repair system once it is induced.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7586190
TI  - Identification of benzo[a]pyrene-7,8-dione as an authentic metabolite of (+/-)
      trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene in isolated rat hepatocytes.
AB  - Dihydrodiol dehydrogenase (DD) has been shown to catalyze the oxidation of (+/-)
      trans-7,8-dihydroxy-7,8-dihydrobenzo [a]pyrene (BP-diol) to yield benzo[a]pyrene
      7,8-dione (BPQ) in uninduced fortified rat liver S100 fractions but the formation
      of BPQ has not been observed in whole cells. In these studies [3H]BP-diol was
      incubated with isolated hepatocytes from uninduced rats for 0-20 min at 37
      degrees C. Organic-extractable radioactivity in the cell media accounted for 20%
      of the total [3H]BP-diol added. Reverse phase (RP)-HPLC analysis of this fraction
      revealed the formation of an unknown metabolite that co-chromatographed with an
      authentic synthetic standard of BPQ. The identity of the unknown metabolite was
      further established by: (i) co-chromatography with synthetic BPQ under both RP-
      and normal phase-HPLC conditions using diode array detection, which indicated
      that metabolite shared UV/vis spectral identity with standard BPQ; and by (ii)
      electron impact mass spectrometry of the unknown metabolite which gave the same
      parent and fragment ions as the synthetic standard. The formation of BPQ by
      isolated hepatocytes was found to be 0.50 nmol/3 x 10(6) cells/10 min, and
      represented 7% of the total organic-soluble metabolites in the extracellular
      media. Its formation was abolished by the addition of indomethacin, a competitive
      inhibitor of DD, indicating that this enzyme was responsible for BPQ formation.
      Other organic-soluble metabolites formed corresponded to BP-tetraols (hydrolysis
      products of the anti- and syn-diol epoxides). Examination of the aqueous phase of
      the extracellular media indicated that a large portion of BP-diol was converted
      to glucuronide and sulfate conjugates. Under the conditions employed BP-tetraols
      and BPQ were formed to an equal extent implying that in hepatocytes isolated from
      uninduced rats, DD and CYP1A1 contributed equally to the metabolism of BP-diol.

PMID- 7586191
TI  - The expression of gap junctional proteins during different stages of mouse skin
      carcinogenesis.
AB  - The loss or alteration of gap junctional intercellular communication (GJIC) has
      long been proposed to play an important role in the process of carcinogenesis. In
      this study we examined the expression of three gap junction proteins, connexins
      (Cx)26, 43 and 31.1, in mouse hyperplastic skin, papillomas and squamous cell
      carcinomas (SCC). Tumors were induced in SENCAR mice by either of two
      initiation/promotion protocols: 7,12-dimethylbenz-[a] anthracene (DMBA)/12-O
      tetradecanoyl-phorbol-13-acetate (TPA) or DMBA/benzoyl-peroxide (BzPo).
      Keratinocytes in adult mouse skin expressed Cx31.1 and Cx43 but did not express
      Cx26. Skin hyperplasia induced by one topical application of TPA was accompanied
      by hyperexpression of both Cx26 and Cx43. In addition, TPA significantly
      inhibited the expression of Cx31.1. After repetitive application. Connexin 26 and
      Cx43 were hyperexpressed in most of the papillomas studied (20-40 weeks after
      initiation). However, in some late papillomas, immunostaining revealed a focal
      loss of Cx26. Immunostaining of mouse skin SCC revealed decreased Cx43 and Cx26
      levels in 65% and 85% of cases respectively. The high levels of Cx26 and Cx43
      mRNA in most of the SCC did not correlate with the decreased abundance or
      disappearance of Cx26 and Cx43 immunoreactive spots from tumor plasma membranes.
      Thus, the expression of these two connexins in SCC was impaired at the post
      translation level. Cx31.1 expression was strongly inhibited during all stages of
      carcinogenesis. Taken together, our results suggest that three different connexin
      genes are differentially regulated during mouse skin carcinogenesis and the
      decrease of connexin expression may be an important marker of skin tumor
      expression.

PMID- 7586192
TI  - Possible mechanisms for PhIP-DNA adduct formation in the mammary gland of female
      Sprague-Dawley rats.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant
      heterocyclic amine in fried beef, is mammary gland carcinogen in rats. Using the
      32P-postlabeling method, PhIP-DNA adduct levels were measured in mammary
      epithelial cells isolated from female Sprague-Dawley rats given 10 daily doses of
      PhIP (75 mg/kg, p.o.) according to a protocol previously shown to induce mammary
      gland cancer. At 24 h, 48 h, 1 week and 5 weeks after the last dose of PhIP, PhIP
      DNA adduct levels [relative adduct labeling (RAL) x 10(7), mean +/- SD] were 10.2
      +/- 0.7, 7.9 +/- 2.7, 2.2 +/- 0.6 and 0.9 +/- 0.03 respectively. When isolated
      rat mammary epithelial cells (from untreated rats) were incubated in vitro with N
      hydroxy-PhIP (45 microM, 1 h, 37 degrees C), PhIP-DNA adducts were detected in
      cell DNA (RAL = approximately 97 x 10(7); however, no adducts were detected in
      cells incubated with PhIP (200 microM, 15 h, 37 degrees C). Incubating cells with
      pentachlorophenol, an inhibitor of acetyltransferase, or incubating cells at 0-4
      degrees C, reduced N-hydroxy-PhIP adduct levels by 45 and 75% respectively,
      indicating that formation of N-hydroxy-PhIP adducts was largely due to metabolic
      activation. Further studies showed that rat mammary gland microsomes had little
      capacity to N-hydroxylate PhIP, as assayed by the mutagenic activation of PhIP in
      the Ames Salmonella assay. In contrast, N-hydroxy-PhIP was metabolically
      activated by cytosol-catalyzed PhIP-DNA adduct formation to calf thymus DNA
      incubated in vitro with N-hydroxy-PhIP (2 microM) in the presence of acetyl CoA.
      Notably, mammary cytosolic O-acetyltransferase activation of N-hydroxy-IQ or N
      hydroxy-MeIQx. All three N-hydroxylamines were activated via cytosolic proline
      aminoacyl-tRNA synthetase and phosphorylase, although the activities of these
      enzymes were approximately 100-fold lower than O-acetyltransferase. No mammary
      cytosolic sulfotransferase activation could be detected with any of the N
      hydroxylamines. Our results are consistent with the notion that PhIP-DNA adduct
      formation and initiation of carcinogenesis in the rat mammary gland may be
      associated with N-hydroxylation of PhIP outside the mammary gland, transport of
      the N-hydroxylamine to the mammary gland and subsequent in situ O
      acetyltransferase-catalyzed activation of N-hydroxy-PhIP.

PMID- 7586193
TI  - Comparison of the effects of tamoxifen and toremifene on liver and kidney tumor
      promotion in female rats.
AB  - Female rats were subjected to a 70% partial hepatectomy and administered either
      diethylnitrosamine (10 mg/kg) or the solvent, trioctanoin. After a 2 day recovery
      from the surgery, the rats were placed on basal diet alone or containing
      phenobarbital (500 mg/kg diet), mestranol (0.2 mg/kg diet), tamoxifen (250 or 500
      mg/kg diet) or toremifene (250, 500 or 750 mg/kg diet) for 6 or 18 months prior
      to killing. The liver and kidneys were prepared for pathological diagnoses. In
      addition, sections of liver from the 6 month killing were frozen and serially
      sectioned. The sections were stained for expression of the placental isozyme of
      glutathione S-transferase (GST), gamma glutamyl transpeptidase (GGT), canalicular
      ATPase (ATP) and glucose 6-phosphatase (G6P) and scored by quantitative
      stereology for number and volume fraction of liver occupied by altered hepatic
      foci (AHF) with alterations in these markers individually and combined (ANY).
      Each of the agents increased the volume fraction of liver occupied by AHF when
      the ANY category was used. Statistical increases in both the GGT-positive and G6P
      deficient AHF populations were observed in the spontaneously as well as DEN
      initiated groups treated with tamoxifen or toremifene. After 18 months of
      administration, the highest concentration of tamoxifen increased the incidence of
      malignant hepatic neoplasms in non-DEN-initiated rats. Toremifene, at the highest
      tested dose, increased the incidence of hepatocellular carcinomas in the DEN
      initiated groups to a level one-third that observed with tamoxifen administration
      to DEN-initiated rats. Both tamoxifen and toremifene increased the incidence of
      hypernephromas in previously DEN-initiated rats. While both tamoxifen and
      toremifene are effective promoting agents for DEN-initiated lesions, tamoxifen is
      more potent than toremifene in the induction of rat hepatocarcinogenesis.

PMID- 7586194
TI  - Effects of sodium ascorbate, sodium saccharin and ammonium chloride on the male
      rat urinary bladder.
AB  - Sodium saccharin administered at high doses to male rats beginning after 5 weeks
      of age produces mild urothelial hyperplasia but does not result in a significant
      increase in incidence of bladder cancer unless it is administered after an
      initiating agent. However, if it is administered in a two-generation bioassay, a
      significant incidence of bladder tumors is produced. The hyperplastic and
      tumorigenic effects are inhibited by co-administration with high doses of NH4Cl.
      The present experiment was designed to evaluate the effects of another sodium
      salt, sodium ascorbate, administered through the neonatal time period. Sodium
      saccharin administered as 5% of the diet produced urothelial hyperplasia and
      increased labeling index, and this was inhibited by co-administration with 1.23%
      NH4Cl. Four doses of sodium ascorbate was evaluated. The lowest dose, 0.91%, was
      without effect on the urinary tract. A slight effect (not statistically
      significant) was observed at a dose of 2.73%, and a significant proliferative
      response was detected at 4.56 and 6.84%. Recent studies suggest that a calcium
      phosphate-containing amorphous precipitate forms in the urine of rats fed high
      doses of sodium saccharin, producing cytotoxicity of the urothelium and
      consequent regenerative hyperplasia. This precipitate was observed in the present
      experiment in the rats administered the high dose of sodium saccharin or the
      higher doses of sodium ascorbate. Formation of this precipitate and induction of
      urothelial proliferation were inhibited by co-administration of NH4Cl, but
      somewhat higher doses of ammonium chloride were required for doses of sodium
      ascorbate compared to sodium saccharin. These results demonstrate that sodium
      ascorbate administered through the neonatal time period of the male rat produces
      urothelial hyperplasia in the dose responsive manner, with a no-effect level of
      0.91% of the diet. The formation of the calcium phosphate-containing amorphous
      precipitate and urothelial proliferation were inhibited by co-administration with
      NH4Cl.

PMID- 7586196
TI  - CYP2D6 genotype and lung cancer risk according to histologic type and tobacco
      exposure.
AB  - Polymorphism for CYP2D6 was determined genetically as part of a hospital-based
      case-control study. The cases were males with a histologically confirmed lung
      cancer diagnosis, < 75 years old, and no previous cancer diagnosis. Male controls
      were matched for age, hospital and residence area. This study includes 301 cases
      and 310 controls. A DNA bank was established for 547 patients (89.5%), and
      genotypes for CYP2D6 were differentiated by the Heim and Meyer method for the DNA
      samples of 249 cases and 271 controls. Among the cases, the frequencies of
      homozygous for the wild-type (EM), heterozygous (HEM) and homozygous for the
      mutant alleles (PM) were 62%, 32% and 7%; among the controls: 57%, 37% and 6%.
      Using EM as the reference, and adjusting for age, hospital and residence, we
      estimated the odds ratios for the HEM group and the PM group at 0.8 (95% CI [0.5
      1.2]) and 1.1 (95% CI [0.5-2.4]) respectively. The PM frequency among the cases
      of adenocarcinoma was twice as high as among the controls (OR = 1.8, 95% CI [0.7
      4.9]). This result was not observed among squamous and small cell carcinoma (OR =
      0.7, 95% CI [0.3-1.8]). Twelve different case-control studies on CYP2D6 and lung
      cancer have so far been performed; the ORs they estimate range from 0.1 to 2.0,
      with a median value of approximately 0.6. This result lends some support to the
      hypothesis that belonging to the PM group is associated with a slight protective
      effect against lung cancer, but does not take into account the possibility that
      results may vary according to histologic type. In this context, the suggestion of
      a positive relationship between CYP2D6 and adenocarcinoma seems to us to merit
      investigation.

PMID- 7586195
TI  - Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase
      aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo
      animal findings.
AB  - Thirteen samples of natural fibres and five samples of man-made fibres (MMF) were
      tested to determine their cytotoxicity and ability to produce chromosome
      missegregation in cultures in rat pleural mesothelial cells (RPMC). The natural
      samples included attapulgite, two amphiboles (amosite and crocidolite); seven
      consisted of chrysotile from various origins and three were obtained after
      chemical treatment of chrysotile. MMF included three refractory ceramic fibres
      (RCF) and two vitreous fibres (MMVF). All fibre samples were characterized by
      electron microscopic measurement of the fibre dimensions. Cytotoxicity was
      assayed on the basis of determination of mitochondrial integrity and chromosome
      missegregation by light microscopy examination of anaphases/telophases. The
      carcinogenic potency of 10 natural samples has been previously investigated using
      intrapleural inoculation in rats. It was therefore possible to establish
      correlations between in vitro and in vivo data obtained with the same set of
      samples. The various samples of chrysotile produced different in vitro effects,
      in agreement with the dispersion of response also observed in vivo. Cytotoxicity
      appears to be dependent on both fibre length and fibre diameter, as the longest
      or thickest fibres were the most toxic. The production of abnormal
      anaphases/telophases appears to depend on the presence of fibres of selected
      size, such as those previously defined by Stanton et al. (L > 8 micrograms; D <
      or = 0.25 microns); a threshold values was determined below which no abnormal
      anaphases/telophases were detected. This non-observable effect level was
      estimated to be 2.5 x 10(5) 'Stanton' fibres per cm2. There was no correlation
      between cytotoxicity and mesothelioma induction; in contrast, a correlation was
      found between the ability of a sample to produce chromosome missegregation in
      vitro and mesothelioma in vivo.

PMID- 7586197
TI  - Inhibition of poly(ADP-ribose) polymerase increases (+/-)-anti-benzo [a]pyrene
      diolepoxide-induced micronuclei formation and p53 accumulation in isolated human
      peripheral blood lymphocytes.
AB  - In response to DNA damage, in particular DNA strand breaks, the proposed roles
      for normal tumour suppressor protein p53 are to increase the period of time
      available for DNA repair prior to replication, or to direct damaged cells into
      programmed cell-death. Since treatment of mammalian cells with (+/-)-anti
      benzo[a]pyrene diolepoxide [(+/-)-anti-BPDE] --a mixture of metabolites
      comprising the most reactive (+)-anti-enantiomer of the full environmental
      carcinogen benzo[a]pyrene--has been shown to result in induction of DNA repair
      processes and consequently in DNA strand break formation, the aim of the present
      study was to investigate whether p53 accumulation is induced in (+/-)-anti-BPDE
      treated phytohaemagglutinin-stimulated human peripheral blood lymphocytes (PBLs).
      Both immunocytochemical and immunoblot analysis indicated that treatment of PBLs
      with (+/-)-anti-BPDE results in p53 accumulation. Optimal accumulation was
      observed at 2.5 microM, while no increase of p53 levels was observed at
      concentrations < 2.5 microM and > 10 microM. Further, (+/-)-anti-BPDE-induced p53
      accumulation in PBLs was found to be time-dependent with accumulation up to 24 h
      after the onset of treatment. Treatment of PBLs with 2.5 microM of (+/-)-anti
      BPDE and 1 mM of 3-aminobenzamide, an inhibitor of the DNA strand break-dependent
      enzyme poly(ADP-ribose) polymerase, resulted in increased p53 levels, in
      comparison to cells treated with (+/-)-anti-BPDE alone. This combination also
      potentiated the frequency of (+/-)-anti-BPDE-induced micronuclei. These findings
      suggest that (+/-)-anti-BPDE-induced DNA strand break formation is responsible
      for the observed p53 accumulation. It is unlikely that poly(ADP-ribose) polymer
      formation is a prerequisite in the process of p53 accumulation, as triggered by
      DNA strand-break inducing agents like (+/-)-anti-BPDE. It is hypothesized that
      p53-dependent pathways may be activated in phytohaemagglutinin-stimulated human
      peripheral blood lymphocytes exposed ex vivo to (+/-)-anti-BPDE.

PMID- 7586200
TI  - DNA-binding and disposition of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine
      (PhIP) in the rat.
AB  - Untreated and Aroclor 1254-pretreated male Wistar rats were given a single dose
      of 1.0 mg/kg body weight of randomly tritium-labelled 2-amino-1-methyl-6
      phenylimidazo[4,5-b] pyridine (3H-PhIP) by oral intubation. Urine and faeces were
      collected at 24, 48 and 72 hours after dosing, and total radioactivity
      determined. At 2, 4, 6, 16, 26, 48 and 72 h, animals were killed and several
      organs, including liver, bladder, lungs, kidney, stomach, large and small
      intestines, heart, thigh muscles, spleen and blood were collected for DNA
      extraction and for determination of total radioactivity. Highest total
      radioactivity at 2 h was not unexpectedly observed in the stomach, small
      intestines and bladder, whereas radiolabels corresponding to approximately 2.5
      nmol PhIP/g of kidney and liver showed the highest levels observed at 24 h.
      Several tissues, including blood, plasma, liver and muscles had a slightly
      bimodal time-distribution of radioactivity showing a second peak at 16-24 h. At
      72 h after a single dose of PhIP, highest radioactivity was observed in the liver
      and the large intestine (0.4 nmol PhIP/g tissue), whereas most other organs,
      irrespective of pretreatment had levels at approximately 0.2 nmol/g of tissue. At
      earlier time points, Aroclor 1254-treated rats had lower amounts of radiolabel in
      all tissues. Radioactivity bound to DNA was determined by high sensitivity
      scintillation counting. In contrast to total radioactivity, DNA-associated
      radioactivity was generally higher in the Aroclor 1254-treated rats, most notably
      in the heart, but levels had decreased to approximately the same level in
      controls and in Aroclor 1254-treated rats at 72 h. DNA-binding was highest at 2-6
      h after dosing, highest in the heart of Aroclor 1254-treated animals at 6 h (120
      adducts/10(8) bases) followed by thigh muscle at 4-6 h (approximately 50
      adducts/10(8) bases, irrespective of pretreatment). Levels were approximately 1.5
      3 times lower in other organs at 2-6 h after dosing. At 72 h, radioactivity
      associated with DNA was again highest in the heart of Aroclor 1254-treated rats
      (20 adducts/10(8) bases) and 5-10 times lower in most other organs, approaching
      the detection limit. Total DNA was extracted from the livers of PhIP dosed rats
      at 4 ad 72 h. DNA was hydrolysed, affinity-concentrated, and analysed by liquid
      chromatography. A radiolabelled peak had identical retention time and UV-spectral
      characteristics as peaks isolated by affinity chromatography and HPLC of acid
      hydrolysed synthetic PhIP-DNA and PhIP-deoxyguanosine adduct.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7586198
TI  - Urinary bladder carcinogenesis induced by melamine in F344 male rats: correlation
      between carcinogenicity and urolith formation.
AB  - Urinary bladder carcinogenesis associated with melamine treatment was examined
      with concomitant use of NaCl to allow assessment of the relationship between
      uroliths and lesion development. Analysis of the chemical composition of calculi
      was also performed. F344/DuCrj male rats received diets containing 3 or 1%
      melamine alone or in combination with either 10 or 5 % NaCl, or 10% NaCl alone
      for 36 weeks, and then diet without NaCl supplement for a further 4 weeks. The
      water intake, used as an index of urinary output, was increased by NaCl
      treatment. The incidences of bladder transitional cell carcinomas and papillomas
      were 90 and 55% in the group treated with 3% melamine alone; 0 and 15% in the
      group treated with 3% melamine and 10% NaCl; and 21 and 42% in group treated with
      1% melamine alone; and zero in the other groups. Calculus formation resulting
      from melamine administration was suppressed dose-dependently by the simultaneous
      NaCl treatment, along with the occurrence of hyperplasia of the papilla in the
      kidneys. The main constituent of calculi were melamine itself and uric acid
      (total contents 61.1-81.2%), contained in equal molar ratio. The results indicate
      that melamine-induced proliferative lesions of the urinary tract of rats were
      directly due to the irritative stimulation of calculi, and not molecular
      interactions between melamine itself or its metabolites with the bladder
      epithelium.

PMID- 7586199
TI  - Mutagenicity of a unique 8-oxoguanine in a human Ha-ras sequence in mammalian
      cells.
AB  - The processing of a unique 8-oxoguanine residue in DNA has been studied in
      mammalian cells using a single-stranded shuttle vector. A fragment of human Ha
      ras carrying the lesion on the first (G1) or the second guanine (G2) of codon 12
      was inserted in a shuttle plasmid. Extrachromosomal DNA is replicated in animal
      cells, extracted and used to transform bacteria to be amplified and
      individualized. DNA sequencing of bacterial clones showed the mutagenic potency
      of 8-oxoguanine in vivo to be approximately 4%. The presence of the 8-oxoguanine
      does not greatly affect survival of the progeny. No significant difference was
      observed between the mutation frequencies induced by 8-oxoguanine located either
      at the G1 or G2 position. The majority of the mutations, targeted at the lesion
      level, are G to T transversions. These base substitutions induced respectively
      glycine to cysteine (G1) or valine (G2) change in the P21ras protein. These
      mutations may contribute to activation of the protooncogene, leading to
      spontaneous tumorigenesis.

PMID- 7586201
TI  - Antibodies to the food mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine
      and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline: useful for immunoassay and
      immunoaffinity chromatography of biological samples.
AB  - Monoclonal mouse IgG1 and IgG3 antibodies were developed to the food mutagens, 2
      amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and 2-amino-3,4,8
      trimethylimidazo[4,4-f] quinoxaline (4,8-DiMeIQx) in order to make specific and
      sensitive detection and purification systems suitable for biological samples. The
      antibodies were developed with the strategy that cross-reaction with analogues
      modified in the N2-position was desirable. Competitive enzyme-linked
      immunosorbent assays (ELISA) with 50% inhibition by 0.4-6 pmol food mutagen were
      developed. The epitopes recognized by the antibodies have been characterized by
      ELISA using 52 synthetic analogues and metabolites of PhIP, 4,8-DiMeIQx, and
      other food mutagens. One of the anti-PhIP antibodies only recognizes PhIP and
      those PhIP-analogues which have minor modifications in the N2-amino group,
      whereas the other, 7B7-1, is less stringent and also recognizes several other
      modified metabolites, including bulky adducts at the N2-amino group e.g. the
      major guanine and deoxyguanosine adducts isolated from PhIP-modified DNA. The
      antibodies to DiMeIQx also recognize the food mutagens 2-amino-3,4
      dimethylimidazo[4,5-f]quinoxaline (4-MeIQx), 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (8-MeIQx), and the corresponding quinolines (4-MeIQ and 8-MeIQ).
      Two of these antibodies only bind analogues with minor modifications in the free
      amino group, whereas analogues with major modifications in this position,
      including a deoxyguanosine adduct, react with the third antibody. Urine samples
      and faecal extracts from 3H-PhIP or 2-14C-DiMeIQx dosed rats were analysed by
      these ELISA assays, and high correlations between radioactivity and response in
      the ELISA assays were observed. Urine samples and faecal extracts from 3H-PhIP
      dosed rats were purified on an affinity column containing the less stringent anti
      PhIP antibody, 7B7-1. The affinity column was found by high performance liquid
      chromatography (HPLC) analysis to concentrate exclusively labelled material. This
      affinity column also bound PhIP-related materials from dilute samples of acid
      hydrolysed PhIP-DNA with high efficiency. Only approximately 40% of the 4,8
      DiMeIQx related materials found in dilute acid hydrolysed samples of 4,8-DiMeIQx
      DNA was bound by an affinity column containing the less stringent anti-4,8
      DiMeIQx antibody, 2C5-1. We conclude that our anti-PhIP and anti-DiMeIQx
      antibodies can be used to determine the presence of these food mutagens and some
      of their activated or conjugated metabolites in complex biological samples.

PMID- 7586203
TI  - Tumorigenicity in newborn mice of fjord region and other sterically hindered diol
      epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[def,p]chrysene), 4H
      cyclopenta[def]chrysene and fluoranthene.
AB  - Diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[def,p]chrysene),
      4H-cyclopenta[def]chrysene and fluoranthene were tested for tumorigenicity in
      newborn mice. The compounds tested were racemic trans-11,12-dihydroxy-anti-13,14
      epoxy-11,12,13, 14-tetrahydrobenzo[g]-chrysene (BgCDE), trans-11, 12-dihydroxy
      anti-13,14-epoxy-11,12,13,14-tetrahydrodibenzo [a,l]pyrene (DB[a,l]PDE), trans
      1,2-dihydroxy-anti-3, 3a-epoxy,1,2,3,3a-tetrahydro-4H-cyclopenta[def]chrysene
      (C[def]C-1,3a-DE), trans-6,7-dihydroxy-anti-8,9-epoxy-10b,1, 2,3
      tetrahydrofluoranthene (FDE). BgCDE and DB[a,l]PDE are fjord region diol epoxides
      and their tumorigenic activities were compared to those of trans-3,4-dihydroxy
      anti-1, 2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE), a fjord region
      diol epoxide with known high tumorigenicity and trans-7,8-dihydroxy-anti-9,10
      epoxy-7,8,9, 10-tetrahydrobenzo[a]-pyrene (BPDE), a highly tumorigenic bay region
      diol epoxide. The protocol called for testing of each compound at a total dose of
      25 nmol per mouse, administered on days 1, 7 and 15 of life, with killing at age
      35 weeks. BgCDE had similar activity as BcPDE for induction of lung tumors and
      was more active than BcPDE for induction of liver tumors in male mice. Both
      compounds were significantly more tumorigenic than BPDE. DB[a,l]PDE was highly
      toxic. All mice died within 1 week of the first dose. It was then tested in a
      second study using total doses of 5 and 1 nmol per mouse. Only the first dose of
      the intended 5 nmol total dose was given due to toxicity. The full course of
      doses with a total of 1 nmol per mouse was administered; DB[a,l]PDE induced a
      significant incidence and multiplicity of lung tumors and, in male mice, liver
      tumors at both doses. These results demonstrate that fjord diol epoxides are
      highly active tumorigens in newborn mice, with activity greater than that of the
      most active unsubstituted bay region diol epoxide, BPDE. C[def]C-1-3a-DE and
      C[def]-6-9-DE were compared to trans-1,2-dihydroxy-anti-3, 4-epoxy-1,2,3,4
      tetrahydrochrysene (CDE), at a total dose of 500 nmol per mouse. FDE was also
      tested at this dose. The most active compound among the chrysene derivatives was
      C[def]C-1-3a-DE, followed by C[def]C-6-9-DE and CDE. C[def]C-1-3a-DE has a
      sterically constrained bay region, in which the benzylic carbon of the tri
      substituted epoxide ring is part of a fused ring system. This feature is also
      present in FDE, which and considerable tumorigenic activity, greater than that of
      CDE in lung and greater than any of the chrysene derivatives in liver.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7586204
TI  - Altered selenium-binding protein levels associated with selenium resistance.
AB  - Our previous studies have sought to elucidate the mechanism by which selenium
      inhibits cell growth since the mechanisms involved may be relevant to the
      chemopreventive properties of selenium. In a previous report, we described the
      isolation of a selenium-resistant cell line, B19, from a selenium-sensitive
      parental cell line, C57. In this report we identify biochemical changes that may
      be responsible for conferring selenium resistance. Altered selenium uptake and
      intracellular glutathione concentrations were eliminated as possible modes of
      resistance since these two parameters were similar between the two cell lines.
      However, when the selenium-containing protein complements of the two cell lines
      were compared by labelling with [75Se]selenite, both increases and decreases in a
      number of selenium-labelling proteins were found in the B19 cells. The most
      striking differences were the presence of two 72 kDa selenium-labelling proteins
      in B19 cells which could not be detected in C57 cells. The levels of a number of
      mRNAs encoding antioxidant or detoxification enzymes were also compared between
      the two cell lines but only minor changes were found. This work suggests that
      further analysis of the 72 kDa selenium-labelling proteins may reveal insights
      into the mechanisms of growth inhibition by selenium.

PMID- 7586202
TI  - Persistence of TCDD-induced hepatic cell proliferation and growth of enzyme
      altered foci after chronic exposure followed by cessation of treatment in DEN
      initiated female rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent tumor promoter in two
      stage models of hepatocarcinogenesis. This study focuses on the persistence or
      reversibility of TCDD-mediated changes in livers after 30 weeks of treatment and
      cessation of treatment. Diethylnitrosamine (DEN) initiated animals (175 mg/kg)
      were promoted bi-weekly with TCDD at a dose equivalent to 125 ng/kg/day for 30
      weeks without or with a following waiting period of 32 weeks before necropsy.
      2,3,7,8-Tetrachlorodibenzo-p-dioxin liver concentration decreased 300-fold above
      background. Induction of CYP1A1 dependent enzyme activity decreased according to
      TCDD tissue levels. In contrast, cell proliferation, as measured by BrdU-labeling
      index, was still 2.8-fold increased over controls in the TCDD group with waiting
      period compared to a 4-fold increase over controls at the end of the 30 week
      dosing period. Enzyme altered hepatic foci expressing the placental form of
      glutathione S-transferase decreased in number but the remaining foci were
      significantly increased in size and the percent of liver occupied by foci was
      higher at the end of the waiting period as compared to livers at the end of the
      dosing period. Liver tumor incidence at the end of the waiting period was 71% (5
      of 7 animals) and the livers showed an increase in bile duct lesions with only
      mild toxicity. There was pronounced bile duct proliferation in DEN/TCDD treated
      animals after the waiting period with intense expression of TGF alpha in bile
      duct epithelial cells at detected by immunohistochemical methods. In comparison,
      at the end of the 30 week dosing period the livers showed more severe toxicity
      and only mild bile duct proliferation. Also, one small hepatocellular adenoma was
      observed. It is concluded that as opposed to CYP1A1 induction the more complex
      biological responses, cell proliferation and selective growth of certain
      preneoplastic foci, are persistent after prolonged TCDD treatment within the
      experimental framework of our study.

PMID- 7586205
TI  - Characterization of a rat oral squamous cell carcinoma cell line UHG-RaC '93
      induced by 4-nitroquinoline-1-oxide in vivo.
AB  - This study describes several characteristics of a cell line, UHG-RaC '93 derived
      from rat oral squamous cell carcinoma induced by the carcinogen 4-nitroquinoline
      1-oxide (4NQO). The cell line was established from explant cultures without
      support of fibroblast feeder cells and continued for > 30 passages. UHG-RaC '93
      had a high mitotic rate with a population doubling time of 25 h and a high rate
      of squame production. The first passage had a low colony-forming efficiency in
      agarose gel, whereas later passages did not grow at all in semi-solid medium.
      Phenotype selection was furthermore apparent from a gradual increase of the
      trypsin-detachment time. Cytogenetic analysis showed that UHG-RaC '93 was
      hypotetraploid with an average of 74 chromosomes. Abnormalities compared to the
      normal karyotype were assessed and consisted mainly of breakpoints at (1)(q5?3),
      (3)(p1), (3)(q11q23), (11)(p?11), (13)(p13) and a derivative
      (12)t(12;13)(q10;q10). The karyotype remained stable for at least 26 passages.
      The expression of typical epithelioid markers like cytokeratins and desmoglein
      corresponded with normal rat oral keratinocytes. However expression of alpha 6
      beta 4-integrin was altered. Squame production, immunophenotype and anchorage
      dependency indicated that UHG-RaC '93 had the same features of a well
      differentiated carcinoma with a low degree of agressiveness as the original
      tumour. The stable karyotype of this cell line provides a basis for further
      analysis of the effect of 4NQO on the genotype, phenotype and behaviour of rat
      oral keratinocytes.

PMID- 7586207
TI  - Carcinogens induce intrachromosomal recombination in human cells.
AB  - A major portion of new cases of cancer may be linked to environmental
      carcinogens. The Ames (Salmonella) test is currently the most widely used short
      term test to predict carcinogenic properties of compounds. However, approximately
      50% of all carcinogens have been sufficiently tested in long-term animal
      bioassays do not induce mutations in the Salmonella assay, and many of these
      carcinogens are also not detectable by other short-term assays. In the work
      described here we determined the effect of carcinogen exposure on
      intrachromosomal recombination in a human cell line. The recombination events
      caused the deletion of one copy of a duplication of exons 2 and 3 of the hprt
      gene. We found that these deletion events were induced by exposure to the
      Salmonella assay positive carcinogens UV, gamma-rays and methyl methanesulfonate,
      as well as the Salmonella assay negative carcinogens Aroclor 1221, benzene and
      thiourea. These data may further support the accumulating evidence that
      recombination and deletions may be important in carcinogenesis.

PMID- 7586208
TI  - Refractoriness to mammary tumorigenesis in parous rats: is it caused by
      persistent changes in the hormonal environment or permanent biochemical
      alterations in the mammary epithelia?
AB  - Administration of a single i.v. injection of 50 mg N-methyl-N-nitrosourea
      (MNU)/kg body wt to 50- to 60-day old virgin rats, 120-day-old virgin rats, and
      120-day-old parous rats (Sprague-Dawley; n = 18-37) resulted in a high incidence
      of mammary carcinomas in the virgin animals (97.3% in 50- to 60-day-old virgin
      rats; 75.0% in 120-day-old virgin rats), but mammary carcinomas did not develop
      in the parous rats. The concentrations in serum of various mammotropic hormones
      were measured in identical groups of rats at the time of MNU treatment. Growth
      hormone (GH) concentration was significantly reduced in parous rats, as compared
      with young or age-matched virgin rats. The concentrations of prolactin, 17 beta
      estradiol, progesterone, corticosterone and thyroxine were not significantly
      altered in the parous rats compared to the two groups of virgin animals.
      Histological examination of the mammary glands from the three groups of rats
      showed that the epithelia of the parous animals were in a stage of regression,
      whereas the mammae of the young virgin rats showed the highest degree of lobulo
      alveolar development. The levels of estrogen receptor (ER), epidermal growth
      factor (EGF) receptor (EGF-R) and GH receptor (GHR) in the mammary glands of the
      animals were also measured. We found a reduction in the receptor levels for both
      estrogen and EGF in mammary tissues from parous animals. Receptors for GH were
      present in normal mammary tissues from both virgin and parous rats. We
      hypothesize that the reduction in the circulating concentration of GH caused the
      reduced susceptibility of parous rats to mammary carcinogenesis possibly by
      decreasing the levels of ER and/or EGF-R in the mammary gland.

PMID- 7586209
TI  - Repair of DNA lesions induced by ultraviolet irradiation and aromatic amines in
      normal and repair-deficient human lymphoblastoid cell lines.
AB  - A host cell reactivation (HCR) assay was employed to study the capacity of a
      normal and three repair-deficient human lymphoblastoid cell lines to repair DNA
      damage induced by UV irradiation and the aromatic amines 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) and N-acetyl-2-aminofluorene (AAF)
      respectively. The cell line belonging to xeroderma pigmentosum complementation
      group C (XP-C) removed all three types of damage less efficiently than the normal
      cell line, but more efficiently than the cell line belonging to xeroderma
      pigmentosum complementation group D (XP-D). The cell line belonging to
      complementation group B of Cockayne's syndrome (CS-B) showed reduced host cell
      reactivation. Fibroblasts from CS-B patients have reduced gene-specific DNA
      repair, but normal total genomic DNA repair, thus our data suggest that the HCR
      assay measures the capacity for gene-specific DNA repair. In the XP-D cell line,
      which had practically no DNA repair capacity, AAF adducts had a more potent
      inhibitory effect on gene expression than UV and PhIP adducts. When corrected for
      this inhibitory effect, the wild-type, XP-C and CS-B cell lines repaired low
      levels of AAF and UV adducts with similar efficiencies, however, PhIP adducts
      were repaired less efficiently.

PMID- 7586206
TI  - Genistein suppresses mammary cancer in rats.
AB  - Female Sprague-Dawley CD rats were injected s.c. with 5 mg genistein, a soy
      phytoestrogen, or 20 microliters of the vehicle, dimethylsulfoxide (DMSO), on
      days 2,4 and 6 postpartum. At day 50, they were exposed to 80 micrograms
      dimethylbenz[a]anthracene (DMBA)/g body wt. Animals treated neonatally with
      genistein as compared to DMSO had increased latency and reduced incidence and
      multiplicity of DMBA-induced mammary adenocarcinomas. Mammary whole mount
      analysis showed that 50 day old female rats treated neonatally with genistein had
      fewer terminal end buds. Cell proliferation studies revealed that 50 day old
      genistein-treated rats had lower percentages and total numbers of cells in the S
      phase of the cell cycle in terminal end buds, terminal ducts, lobules I and
      lobules II. In genistein-treated as compared to vehicle-treated female rats,
      vaginal openings occurred earlier, the estrus cycle was disrupted and the uterine
      ovarian weights were smaller. In 50 day old genistein-treated females there were
      atretic antral follicles, fewer corpora lutea, and lower circulating progesterone
      but not estradiol-17 beta concentrations. In 21 day old rats treated neonatally
      with genistein, mammary glands were larger and there were more terminal end buds
      and terminal ducts, and more proliferative activity in all terminal ductals
      structures. It appears that neonatal genistein-treatment exerted its
      chemoprevention action by acting directly to enhance maturation of terminal
      ductal structures and by altering the endocrine system to reduce cell
      proliferation in the mammary gland.

PMID- 7586210
TI  - Lower levels of urinary 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) in
      humans with higher CYP1A2 activity.
AB  - Heterocyclic aromatics amines (HAAs), such as 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx), are metabolically activated by cytochrome P4501A2 (CYP1A2)
      and N-acetyltransferase (NAT2). We examined the relationship between CYP1A2 and
      NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy
      subjects. The subjects ate a control diet for 7 days containing lean ground beef
      cooked at low temperature. On day 8, they were tested for CYP1A2 and NAT2
      activity by caffeine phenotyping. On the evening of day 8, subjects consumed lean
      ground beef cooked at high temperature containing 9.0 ng of MeIQx/g of meat. The
      subjects ate 3.1-4.0 g meat/kg body wt. Twelve-hour urine samples were collected
      and MeIQx was measured by gas chromatography-mass spectrometry. Using linear
      regression analyses, we found that higher CYP1A2 activity was associated with
      lower levels of total unconjugated MeIQx in the urine (P = 0.008) when adjusted
      for amount of meat eaten, while NAT2 activity showed no relationship with the
      latter. This suggest that a greater percentage of MeIQx is converted to
      metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher. This
      finding supports the concept that inter-individual variation is CYP1A2 activity
      may be relevant for cancers associated with exposure to HAAs.

PMID- 7586211
TI  - Differential sensitivity to loss of cytosine methyl groups within the hepatic p53
      gene of folate/methyl deficient rats.
AB  - Dietary folate/methyl deficiency provides a unique model of endogenous
      hepatocarcinogenesis in which to study progressive alterations in DNA methylation
      patterns during tumor progression in vivo. Weanling male F344 rats were given a
      semi-purified diet deficient in the methyl donors choline, methionine and folic
      acid for a period of 9 weeks. Using a genomic sequencing procedure based on the
      PCR amplification of bisulfite-modified DNA, the methylation status of individual
      CpG sites within exons 6 and 7 of the p53 gene in liver samples from control and
      deficient rats was determined. Treatment of denatured nuclear DNA with sodium
      bisulfite quantitatively converts all cytosine residues to uracil which are then
      amplified as thymine in the PCR reaction. In contrast, 5-methylcytosine is
      resistant to bisulfite deamination under the reaction conditions and is amplified
      as cytosine. Automated sequencing of bisulfite-modified DNA will then elucidate
      the methylation status of each cytosine residue within a defined gene sequence.
      In addition to evaluation of the methylation status of the p53 gene, the relative
      activity of the DNA methyltransferase was also quantified in nuclear extracts
      from control and folate/methyl deficient rats. The results indicate that specific
      5-methyl cytosines within the hepatic p53 gene from methyl deficient rats are
      resistant to demethylation despite the diet-induced decrease in S
      adenosylmethionine and the increase in cell proliferation associated with this
      dietary intervention. Progressive demethylation was observed at other methylated
      cytosine residues in folate/methyl deficient rats after 9 weeks despite a
      paradoxical increase in DNA methyltransferase activity. The application of this
      sequence-specific technology will allow the definition of the methylation status
      of every CpG site within a coding sequence or promoter region and should provide
      new insights into mechanisms and consequences of methylation dysregulation during
      progressive multistage carcinogenesis.

PMID- 7586212
TI  - Mutagenic specificity of syn-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide in
      the dihydrofolate reductase gene of Chinese hamster ovary cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) with sterically hindered fjord region
      diol epoxides are interesting with respect to their potency as carcinogens,
      interactions with DNA and mutagenic specificities. Unlike the bay region PAH
      derivative, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10
      tetrahydroxybenzo[a]pyrene (BPDE), reactive metabolites of two fjord region PAH,
      trans-3,4-dihydroxy-anti-1, 2-epoxy-1,2,3,4-tetrahydrobenzo[c]-phenanthrene [(+/
      )-anti-BcPHDE] and trans-11,12-dihydroxy-syn-BgCDE], react with DNA to yield high
      levels of adenine adducts. We previously found that forward mutations induced by
      (+/-)-anti-BcPHDE in the dihydrofolate reductase (dhfr) gene of Chinese hamster
      ovary (CHO) cells preferentially targeted mRNA splice acceptor sites. (+/-)-anti
      BcPHDE and (+/-)-syn-BgCDE are structurally similar; they differ only by the
      presence of an additional benzene ring. Thus we used (+/-)-syn-BgCDE to learn if
      the mutational target bias reflects aspects of the mutagen structure or its
      capacity to efficiently modify deoxyadenosine (dA) in vivo. dhfr(-) mutants were
      induced after treatment of hemizygous UA21 cells with a 0.75 microM dose of (+/-)
      syn-BgCDE. Cell survival after carcinogen exposure was 40%. The induced mutation
      frequency was 9 x 10(-6), nearly 10-fold higher than the spontaneous one, but
      approximately 19-fold lower than formerly observed using (+/-)-anti-BcPHDE. In
      the 26 confirmed null dhfr(-) mutants 27 mutations were identified by DNA
      sequencing. The types of (+/-)-syn-BgCDE-induced mutations were very similar to
      those formerly induced by (+/-)-anti-BcPHDE. Consistent with the binding
      specificity, both chemicals induced transversion base substitution at purines (R-
      >T). The most prevalent type of mutation was A-->T, which represented 59% of the
      induced changes, compared with 42% for (+/-)-anti-BcPHDE. (+/-)-syn-BgCDE mutated
      mostly novel targets in the dhfr gene, sites not found mutated with any of the
      several other mutagens we have used in former studies. Whereas the 25 kg dhfr
      gene contains six coding exons, the majority (16/27) of (+/-)-syn-BgCDE-induced
      mutations were located in a single one (exon 4). A random distribution of
      mutations affecting splice acceptor sites (22%) was induced by (+/-)-syn-BgCDE.
      Hence, preferential mutation of these sites by (+/-)-anti-BcPHDE may reflect
      aspects of chromatin structure in vivo which make these sequences better targets
      for modification. Alternatively, the sequence context of these sites may dictate
      an adduct conformation which is poorer for damage recognition and/or efficient
      repair.

PMID- 7586213
TI  - Gender differences in the metabolism of 1,3-butadiene in Sprague-Dawley rats
      following a low level inhalation exposure.
AB  - 1,3-Butadiene (BD), a compound used extensively in the rubber industry, is
      carcinogenic in the male and female Sprague-Dawley rats after chronic exposures
      to 1000 and 8000 p.p.m. In terms of incidence of tumors the majority were in
      mammary tissue, thus the incidence of tumors in female rats exceeded that in
      males in chronic carcinogenicity studies. In the present study the production and
      disposition of butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2),
      mutagenic BD metabolites, were examined in male and female Sprague-Dawley rats
      following a low level inhalation exposure to BD. The rats were exposed to a
      target concentration of 62.5 p.p.m. BD by nasal inhalation for 6 h. Immediately
      after exposure blood, bone marrow, lung and fat samples were removed from all the
      animals and mammary tissue was removed from females. The samples were prepared by
      cryogenic-vacuum line distillation and analyzed for the epoxides using
      multidimensional gas chromatography-mass spectrometry. Levels of BDO in the blood
      were 25.9 +/- 2.9 and 29.4 +/- 2 pmol/g in male and females respectively. The
      levels of this metabolite were also similar in males and females in the other
      tissues examined. The greatest amounts of BDO were in fat (175 +/- 21 and 203 +/-
      13 pmol/g in males and females respectively). Levels of BDO2 were approximately 5
      fold greater in the blood of female rats compared with male rats. In the other
      tissues examined BDO2 was also consistently greater in tissues from females. In
      fat BDO2 was present at a concentration of 7.7 +/- 1.3 and 1.1 +/- 0.1 pmol/g
      tissue in females and males respectively. Mammary tissue from female rats
      contained 10.5 +/- 2.4 pmol/g BDO2, a level slightly lower than that observed in
      blood. The ratios of the two epoxides differed markedly between males and females
      in all tissues examined. Differences were most pronounced in lung and fat
      tissues, where BDO/BDO2 ratios were 9 and 0.6 (lung) and 159 and 26 (fat) for
      males and females respectively. This study is the first to describe a gender
      difference in the metabolism of BD. The greater production of the highly
      mutagenic BDO2 in females may play a role in the increased incidence of mammary
      tumors after chronic exposure to BD.

PMID- 7586214
TI  - p53 mutations in primary hepatic angiosarcomas not associated with vinyl chloride
      exposure.
AB  - Angiosarcomas of the liver are rare, malignant cancers composed of neoplastic
      blood vessels. Human hapatic angiosarcomas have been associated with liver
      cirrhosis or exposure to vinyl chloride, Thorotrast or arsenic. A recent analysis
      of six hepatic angiosarcomas associated with vinal chloride exposure found three
      mutations and all were A:T --> T:A transversions, which are otherwise uncommon in
      human cancers. To test the specificity of this mutation spectrum, we analyzed 21
      hepatic angiosarcomas not associated with vinyl chloride exposure. Four cases
      were exposed to Thorotrast, none had a history of arsenic exposure and the rest
      were sporadic. Exons 5-8 of the p53 gene were amplified by polymerase chain
      reaction, and the products were sequenced directly. Two G:C --> A:T transitions
      were found in two tumors: TGCstop in codon 136. Neither mutation was associated
      with Thorotrast exposure. These data indicate that p53 mutations are uncommon in
      sporadic hepatic angiosarcomas (2/21, 9%), and the mutational profile is
      consistent with endogenous mechanisms. Both features support the evidence linking
      vinyl chloride exposure to hepatic angiosarcomas containing an increased
      frequency of p53 mutations with a mutational spectrum (i.e. A:T --> T:A
      transversions) characteristic of chloroethylene oxide, a carcinogenic metabolite
      of vinyl chloride.

PMID- 7586216
TI  - Angiotensin II activates pp60c-src in vascular smooth muscle cells.
AB  - The angiotensin II type-1 (AT1) receptor, a G protein-coupled receptor, lacks
      intrinsic kinase activity. However, recent data show that angiotensin II (Ang II)
      stimulates tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1),
      Stat91 (one of the signal transducers and activators of transcription), and
      paxillin in vascular smooth muscle cells. The tyrosine kinases responsible for
      these phosphorylation events are unknown. Src family kinases have been shown to
      phosphorylate PLC-gamma 1 and to be activated by G protein-coupled receptors. We
      hypothesized that pp60c-src associates with the AT1 receptor and is activated
      after Ang II stimulation of smooth muscle cells. We immunoprecipitated pp60c-src
      from Ang II-stimulated vascular smooth muscle cells and measured pp60c-src
      activity by autophosphorylation and by phosphorylation of enolase. Both assays
      demonstrated an approximately threefold increase in pp60c-src activity within 1
      minute. A similar increase in Ang II-stimulated pp60c-src activity was observed
      in Chinese hamster ovary cells transfected with the AT1 receptor but not in
      untransfected cells. These data are the first to show that pp60c-src is activated
      by Ang II. To determine if pp60c-src associated with the AT1 receptor, the AT1
      receptor was immunoprecipitated (with two different antibodies), and Western
      blots were performed with two different anti-pp60c-src antibodies. No pp60c-src
      was detected. In addition, direct interaction between the AT1 receptor and pp60c
      src could not be demonstrated by using a glutathione S-transferase (GST)-AT1
      fusion protein to bind proteins from cell lysates stimulated by Ang II.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7586217
TI  - Involvement of multiple cis elements in basal- and alpha-adrenergic agonist
      inducible atrial natriuretic factor transcription. Roles for serum response
      elements and an SP-1-like element.
AB  - In the present study, cis elements in the 5'-flanking sequence (FS) of the rat
      atrial natriuretic factor (ANF) gene involved in regulating basal and alpha 1
      adrenergic-inducible transcription were investigated. Truncation analyses using
      ANF-luciferase reporter constructs transfected into primary neonatal rat cardiac
      myocytes showed that an A/T-rich serum response element (SRE) at -114 bp of the
      ANF 5'-FS, which bound serum response factor (SRF), was required for basal and
      inducible transcription. In constructs composed of 134 bp of rat ANF 5'-FS
      driving luciferase (ANF-134Luc), mutations in the SRE at -114 bp disrupted SRF
      binding and ANF promoter activity. However, the same mutations in ANF-638Luc had
      little effect, suggesting a collaborating role for more distal sequences, such as
      the other SRE in ANF-638 at -406 bp. In ANF-638Luc, mutations in the SRE at -406
      bp that disrupted SRF binding to that site decreased ANF reporter activity by
      only 25%; however, mutating both of the SREs completely blocked alpha 1
      adrenergic-inducible activity. Mutation analyses showed that an ... (SP-1)-like
      site at -69 bp, shown previously to confer inducibility in reporters with 134 bp
      of ANF 5'-FS, was not required in ANF-638Luc. However, double mutants in the SP-1
      like region and either SRE completely blocked alpha 1-adrenergic-inducible ANF
      promoter activity. These findings emphasize that no single element is responsible
      for alpha 1-adrenergic agonist-regulated ANF transcription but that the SREs at 
      114 and -406 bp and the SP-1-like sequence at -69 bp mediate the effect in
      collaboration.

PMID- 7586215
TI  - Rapamycin selectively inhibits angiotensin II-induced increase in protein
      synthesis in cardiac myocytes in vitro. Potential role of 70-kD S6 kinase in
      angiotensin II-induced cardiac hypertrophy.
AB  - It has been suggested that phosphorylation of a 40S ribosomal protein, S6,
      regulates protein synthesis. Two distinct families of S6 kinase have been
      identified, the rsk-encoded 85- to 92-kD S6 kinase (RSK) and the 70- or 85-kD S6
      kinase (p70S6K). We have previously shown that hypertrophic stimuli, such as
      angiotensin II (Ang II), rapidly activate RSK in cardiac myocytes. However, RSK
      and p70S6K are regulated by distinct mechanisms, and p70S6K, but not RSK, is the
      physiological S6 kinase in vivo in other cell types. Using cultured neonatal rat
      ventricular myocytes, we examined whether Ang II activates p70S6K and
      investigated the effect of rapamycin, a potent yet indirect inhibitor of p70S6K,
      on the Ang II-induced hypertrophic response. Immunoblot analyses indicate that
      cardiac myocytes express the 70- and 85-kD forms of p70s6K. Ang II caused a rapid
      and sustained activation of p70S6K through the type I Ang II receptor. Rapamycin
      inhibited Ang II-induced activation of p70S6K in a dose-dependent manner, with an
      IC50 of 0.14 ng/mL (0.15 nmol/L). Rapamycin did not inhibit Ang II-induced
      activation of tyrosine kinase, mitogen-activated protein kinase, RSK, and protein
      kinase C. The effect of rapamycin is unlikely to be mediated by its effect on
      p34cdc2 and p33cdk2 because Ang II did not activate these cell cycle-dependent
      kinases in cardiac myocytes. In contrast, a dose-dependent inhibition of p70S6K
      by rapamycin is very closely correlated with its inhibition of the Ang II-induced
      increase in protein synthesis. Interestingly, rapamycin did not affect the Ang II
      induced activation of specific gene expression, including the immediate-early
      gene c-fos and fetal type genes, such as atrial natriuretic factor and skeletal
      alpha-actin. Moreover, rapamycin did not suppress Ang II-induced phenotypic
      changes at the protein level, such as increased atrial natriuretic factor
      secretion, expression of beta-myosin heavy chain, and organization of actin into
      sarcomeric units. These results indicate that p70S6K is activated by Ang II and
      that a rapamycin-sensitive signaling mechanism, most likely p70S6K, plays an
      essential role in the Ang II-induced increase in overall protein synthesis but
      not in Ang II-induced specific phenotypic changes in cardiac myocytes.

PMID- 7586219
TI  - VEGF165 expressed by a replication-deficient recombinant adenovirus vector
      induces angiogenesis in vivo.
AB  - To evaluate the concept that localized delivery of angiogenic factors via virus
      mediated gene transfer may be useful in the treatment of ischemic disorders, the
      replication-deficient adenovirus (Ad) vector AdCMV.VEGF165 (where CMV is
      cytomegalovirus and VEGF is vascular endothelial growth factor) containing the
      cDNA for human VEGF165, a secreted endothelial cell-specific angiogenic growth
      factor, was constructed. Human umbilical vein endothelial cells (HUVECs) and rat
      aorta smooth muscle cells (RASMCs) infected with AdCMV.VEGF165 (5 and 20 plaque
      forming units [pfu] per cell) demonstrated VEGF mRNA expression and protein
      secretion into the supernatant. Furthermore, the conditioned medium from these
      cells enhanced vascular permeability in vivo. In contrast, neither VEGF mRNA nor
      secreted protein was found in uninfected HUVECs or RASMCs or in cells infected
      with the control vector AdCMV.beta gal (where beta gal is beta-galactosidase).
      Assessment of starved HUVECs at 14 days demonstrated sixfold more cells for
      AdCMV.VEGF165-infected HUVECs (20 pfu per cell) than for either infected or
      uninfected control cells. RASMC proliferation was unaffected by infection with
      AdCMV.VEGF165. When plated in 2% serum on dishes precoated with reconstituted
      basement membrane (Matrigel), HUVECs infected with AdCMV.VEGF165 (20 pfu per
      cell) differentiated into capillary-like structures. Under similar conditions,
      both uninfected HUVECs and HUVECs infected with AdCMV.beta gal did not
      differentiate. To evaluate the ability of AdCMV.VEGF165 to function in vivo,
      either AdCMV. VEGF165 or AdCMV.beta gal (2 x 10(10) pfu) was resuspended in 0.5
      mL Matrigel and injected subcutaneously into mice. Immunohistochemical staining
      demonstrated VEGF in the tissues surrounding the Matrigel plugs containing
      AdCMV.VEGF165 up to 3 weeks after injection, whereas no VEGF was found in the
      control plugs with AdCMV.beta gal. Two weeks after injection, there was
      histological evidence of neovascularization in the tissues surrounding the
      Matrigel containing AdCMV.VEGF165, whereas no significant angiogenesis was
      observed in response to AdCMV.beta gal. Furthermore, the Matrigel plugs with
      AdCMV.VEGF165 demonstrated hemoglobin content fourfold higher than the plugs with
      AdCMV.beta gal. Together, these in vitro and in vivo studies are consistent with
      the concept that Ad vectors may provide a useful strategy for efficient local
      delivery of VEGF165 in the treatment of ischemic diseases.

PMID- 7586220
TI  - Identification of receptor binding and activation sites in endothelin-1 by use of
      site-directed mutagenesis.
AB  - This study addresses the structural requirements for the intracellular processing
      and receptor binding properties of endothelin-1 (ET-1). Point mutants of
      preproendothelin-1 cDNA, with replacement of the codons for Lys9 of ET-1 by ones
      for Ala and Glu and of Ile20 and Trp21 by ones encoding Ala, were expressed in
      COS-7 cells. Competitive binding experiments on rat vascular smooth muscle cells
      (A-10), which were shown to be an ETA receptor-rich cell line, between [125I]ET-1
      and synthetic ET-1, wild-type recombinant ET-1, and recombinant [Ala9]ET-1,
      [Glu9]ET-1, [Ala20]ET-1, and [Ala21]ET-1 yielded Ki values of 0.2 +/- 0.02, 0.2
      +/- 0.02, 0.04 +/- 0.01, 1.4 +/- 0.2, 1.6 +/- 0.2, and > 50 nmol/L, respectively.
      In similar experiments with ETB receptor-rich human Girardi heart cells, the
      corresponding values were 0.2 +/- 0.03, 0.2 +/- 0.03, 0.2 +/- 0.04, 0.2 +/- 0.06,
      1.4 +/- 0.4, and > 50 nmol/L. The ETA receptor-mediated contractile responses to
      [Glu9]ET-1 and [Ala20]ET-1, measured by using canine coronary artery rings, were
      decreased approximately fourfold to fivefold compared with the response produced
      by synthetic or wild-type recombinant ET-1, whereas [Ala9]ET-1 was found to be
      more potent, and [Ala21]ET-1 did not produce any contraction. These results
      demonstrate that Ile20 and Trp21 are involved in binding to both receptor
      subtypes. Of considerable interest was the observation that [Glu9]ET-1 also
      blunts the ETA receptor subtype-mediated contractile response to ET-1 stimulus.

PMID- 7586218
TI  - Multiple growth factors modulate mRNA expression of angiotensin II type-2
      receptor in R3T3 cells.
AB  - Previous studies showed that angiotensin II type-2 receptor (AT2) sites were
      increased when R3T3 cells were growth arrested and decreased when they were
      stimulated with fibroblast growth factor or serum. We examined the effects of
      several other growth factors on the expression of AT2 mRNA to clarify the
      relation between the AT2 receptor and growth factors. R3T3 cells were cultured in
      the medium containing 10% FCS until they were confluent and then serum was
      removed. AT2 mRNA was increased after serum was depleted, and the expression
      level reached a plateau after 2 days of serum depletion. The presence of serum
      (10%), fibroblast growth factor (10 ng/mL), or lysophosphatidic acid (1 mumol/L)
      reduced the AT2 mRNA expression. Phorbol ester (1 to 100 nmol/L) also suppressed
      the AT2 mRNA expression in a dose-dependent manner. Interleukin-1 beta (1 ng/mL)
      enhanced the AT2 mRNA expression 1.6-fold and the AT2 receptor number 1.4-fold.
      Insulin (100 nmol/L) enhanced AT2 mRNA expression 1.4-fold and the AT2 receptor
      number 1.6-fold. These results suggest that AT2 mRNA expression is modulated by
      multiple growth factors in both positive and negative directions. The presence of
      potential cis DNA elements that respond to interleukin-1 beta (CCAAT enhancer
      binding protein site), insulin [insulin response sequence of
      phospho(enol)pyruvate carboxykinase gene], and phorbol ester (AP-1 site) in the
      promoter region of the mouse AT2 gene suggests that the effects of these growth
      factors and phorbol ester may be mediated via these cis DNA elements.

PMID- 7586222
TI  - Decreased elastin synthesis in normal development and in long-term aortic organ
      and cell cultures is related to rapid and selective destabilization of mRNA for
      elastin.
AB  - We have previously shown that aortic organ cultures from 1- to 3-day-old chickens
      initially mimic the high levels of elastin production seen in vivo. However, more
      prolonged incubation of these tissues results in decreased synthesis of elastin.
      In the present study, we demonstrate that decreased production of elastin in
      these aortic organ cultures is selective for elastin compared with collagen and
      is correlated with decreased steady state levels of mRNA for elastin. These
      decreases in steady state levels of elastin mRNA are due at least in part to a
      rapid and selective destabilization of mRNA for elastin, the half-life of which
      falls from approximately 25 hours in fresh aortic tissues to approximately 15
      hours after incubation for only 8 hours. Destabilization of elastin mRNA can be
      prevented by incubation in the presence of blockers of DNA transcription (5,6
      dichlorobenzimidazole riboside and actinomycin D) and mRNA translation
      (cycloheximide). Furthermore, the half-life of aortic elastin mRNA decreases from
      approximately 25 hours in the 1-day-old chicken to approximately 7 hours in the 8
      week-old chicken, demonstrating that destabilization of mRNA is an important
      contributing factor in the decline in production of aortic elastin taking place
      during normal postnatal growth.

PMID- 7586223
TI  - Divergent mechanisms of ATP-sensitive K+ channel-induced vasodilation in renal
      afferent and efferent arterioles. Evidence of L-type Ca2+ channel-dependent and 
      independent actions of pinacidil.
AB  - K+ channel openers (PCOs), such as pinacidil, elicit vasodilation primarily by
      hyperpolarization-induced inhibition of L-type Ca2+ channel activation. The
      physiological role of other mechanisms suggested to contribute to PCO-induced
      vasodilation is not well established. In the renal microcirculation, L-type Ca2+
      channels play a prominent role in vasoconstriction of the afferent arteriole (AA)
      but are absent or physiologically silent in the efferent arteriole (EA). Thus, L
      type Ca2+ channel-dependent and -independent mechanisms can readily be
      distinguished in this model. In the present study, we found that pinacidil
      potently inhibited Bay K 8644-induced AA vasoconstriction. Pinacidil also
      preferentially inhibited angiotensin II-induced AA vasoconstriction
      (approximately ninefold greater potency than EA). These results are consistent
      with an AA effect of pinacidil on L-type Ca2+ channel activation. Unexpectedly,
      10 mumol/L pinacidil inhibited AA and EA responses to similar extents (84 +/- 10%
      and 71 +/- 9%, respectively). In both AAs and EAs, glibenclamide restored normal
      reactivity, indicating an involvement of the ATP-sensitive K+ channels. In the
      EA, however, pretreatment with diltiazem did not alter the effects of pinacidil.
      Nevertheless, 45 mmol/L KCl reversed the EA actions of pinacidil, indicating an
      essential requirement for a normal K+ gradient. These findings suggest that the
      EA actions of pinacidil involve alterations in membrane potential but not changes
      in L-type Ca2+ channel activity. Overall, our findings do support the premise
      that L-type Ca2+ channel modulation is involved in PCO-induced vasodilation in
      the renal microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586225
TI  - Alpha-v beta-3 integrin expression in normal and atherosclerotic artery.
AB  - Recent evidence suggests that alpha v beta 3 integrin is a critical molecule in
      several processes involved in atherosclerosis progression and in restenosis, eg,
      smooth muscle cell (SMC) migration and angiogenesis. While several ligands for
      this integrin are known to be present in atherosclerotic plaque, little is known
      about the presence of alpha v beta 3 integrin at this site. In the present study,
      we have examined alpha v beta 3 expression in normal and atherosclerotic
      arteries. Thirty-six coronary artery segments from the recipient hearts of 24
      patients undergoing heart transplantation were classified into two groups:
      nonatherosclerotic diffuse intimal thickening (DIT) and atherosclerotic plaques.
      Serial frozen sections were examined immunohistochemically with four different
      monoclonal antibodies directed against human alpha v beta 3 complex or the beta 3
      subunit and with cell markers for SMCs, macrophages, and endothelial cells. The
      endothelium along the lumen of both DIT and plaque arteries showed high
      expression of alpha v beta 3. The media of both DIT and plaque arteries showed
      less intense but extensive expression of alpha v beta 3. Immunoprecipitation and
      reverse-transcribed polymerase chain reaction (RT-PCR) analyses performed on
      extracts from the aortic media confirmed the presence of alpha v beta 3 in the
      media. In the intima of both DIT and plaque arteries, alpha v beta 3 expression
      generally colocalized with SMCs but rarely with macrophages. The microvessels in
      the adventitia as well as in the plaque showed prominent expression of alpha v
      beta 3, in contrast to low expression in similar-sized microvessels of the
      skin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586224
TI  - Mononuclear leukocytes invade rabbit arterial intima during thickening formation
      via CD18-and VLA-4-dependent mechanisms and stimulate smooth muscle migration.
AB  - The role of mononuclear leukocytes for the migration of smooth muscle cells
      (SMCs) during intimal thickening was investigated in the rabbit model of
      electrically stimulated carotid artery. The approach was to inhibit leukocyte
      entry into the arterial intima with antibodies against the adhesion molecules
      very late activation antigen-4 (VLA-4) and CD11/CD18. In electrically stimulated
      control rabbits treated either with saline or a nonspecific antibody, all types
      of granulocytes, monocytes, and lymphocytes migrated across an intact endothelium
      into the acellular subendothelial space, followed by the movement of SMCs from
      the media into the intima within 36 hours of applying electrical current.
      Treatment of the rabbits with monoclonal antibody (mAb) HP1/2 directed toward the
      alpha 4 subunit (CD49d) of VLA-4 inhibited mononuclear leukocyte invasion
      (consisting of monocytes and lymphocytes) by approximately 70% compared with the
      IgG-treated control rabbits and completely abolished the minimal influx of
      basophils and eosinophils after 36 hours. Neutrophil infiltration, however,
      remained unaffected by anti-VLA-alpha 4 treatment. Under these conditions, SMC
      migration across the internal elastic lamina was reduced by 50%. The use of mAb
      HP1/2 together with mAb 60.3 (directed to the beta 2 chain of CD11/CD18)
      completely abolished the influx of monocytes, lymphocytes, and all types of
      granulocytes into the arterial intima. This complete blockade of leukocyte
      infiltration resulted in a 70% reduction of intimal SMC accumulation. Together
      with our previous findings excluding neutrophils as stimulators of SMC migration,
      the present results indicate that mononuclear leukocyte promote lesion
      development by stimulating SMC migration.

PMID- 7586221
TI  - T-cell lymphokines, interleukin-4 and gamma interferon, modulate the induction of
      vascular smooth muscle cell tissue plasminogen activator and migration by serum
      and platelet-derived growth factor.
AB  - Platelet-derived growth factor (PDGF)-induced smooth muscle cell (SMC)
      fibrinolysis is necessary for SMC migration. In order to determine whether the T
      cell lymphokines interleukin-4 (IL-4) and gamma interferon (gamma-IFN) affect SMC
      fibrinolysis and migration, we examined the effects of human recombinant IL-4 and
      gamma-IFN on human aortic SMC tissue-type plasminogen activator (TPA), urokinase
      type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI
      1) antigen production, as determined by enzyme-linked immunosorbent assays.
      Although IL-4 had no direct effect on SMC TPA antigen, IL-4 potentiated SMC TPA
      antigen levels and activity in conditioned media and cellular lysates in media
      containing 2% fetal bovine serum but did not change UPA or PAI-1 production.
      gamma-IFN attenuated IL-4 augmentation of SMC TPA antigen production in
      conditioned media, although gamma-IFN itself had no direct effects on SMC TPA and
      PAI-1 antigen production. IL-4 augmented PDGF induction of SMC TPA antigen. gamma
      IFN inhibited PDGF induction of SMC TPA antigen and IL-4 potentiation of this
      process. gamma-IFN diminished the promigratory effects of both IL-4 and PDGF on
      in vitro SMC migration. Tranexamic acid, a plasmin inhibitor, abrogated the
      stimulation of SMC migration by IL-4. Therefore, IL-4 and gamma-IFN modulate the
      induction of SMC TPA and SMC migration by 2% fetal bovine serum and PDGF.

PMID- 7586226
TI  - Binding and phagocytosis of apoptotic vascular smooth muscle cells is mediated in
      part by exposure of phosphatidylserine.
AB  - Apoptosis of vascular smooth muscle cells has recently been demonstrated to occur
      in vitro and in vivo. Uptake of apoptotic cells into adjacent normal cells
      appears to be rapid and specific. We have investigated binding and phagocytosis
      of apoptotic vascular smooth muscle cells by normal smooth muscle cell
      monolayers. Vascular smooth muscle cells were infected with the proto-oncogene c
      myc or the adenovirus E1A gene, induced to undergo apoptosis in low-serum
      conditions, and then incubated with normal smooth muscle cells. Apoptosis was
      accompanied by a marked increase in exposure of phosphatidylserine on the outer
      surface of the cell, which was recognized by binding to annexin V. Liposomes
      containing phosphatidylserine but not phosphatidylinositol inhibited uptake of
      apoptotic cells in a dose-dependent manner to a maximum of 50% inhibition;
      annexin V also inhibited the uptake of apoptotic cells in a dose-dependent and
      calcium-dependent manner. Binding of apoptotic bodies did not appear to be
      mediated by endogenous annexin V, as evidenced by the inability of an antibody to
      annexin V to inhibit uptake. Smooth muscle cells were also able to recognize
      exposed phosphatidylserine on other cell types, as judged by their ability to
      bind erythrocytes having a high degree of exposed phosphatidylserine. We conclude
      that smooth muscle cells express phosphatidylserine during apoptosis, and this
      exposure partly mediates binding and phagocytosis of dead cells. This mechanism
      may be important in promoting rapid cell removal in the vessel wall.

PMID- 7586227
TI  - Mechanisms of transmural heparin transport in the rat abdominal aorta after local
      vascular delivery.
AB  - Local vascular drug delivery systems provide elevated concentrations in target
      arterial tissues, while minimizing systemic side effects. Drug can now be
      released to isolated arterial segments from the endovascular or perivascular
      aspects of the blood vessel, yet the forces that determine drug distribution and
      deposition for these different modes of delivery have not been rigorously
      investigated. This study examines mechanisms of transmural transport of a model
      vasoactive drug, heparin, and compares estimates of the distribution after
      administration from either aspect of the artery. We showed that (1) heparin
      traversed the arterial wall rapidly; (2) diffusion far outweighed convection in
      the control of transmural heparin transport in the normal artery, but after
      endothelial injury, convective forces rose to one quarter the magnitude of
      diffusive forces; (3) the endothelium posed a minimal diffusive barrier to
      heparin; and (4) the diffusive barrier imposed by the adventitia depended on its
      thickness. These findings strongly suggest that vasoregulatory compounds can be
      administered to target tissue by either perivascular or endovascular means with
      equal efficacy, because the forces governing transport of heparin from either
      aspect of the blood vessel wall are not significantly different. Furthermore, the
      differences in arterial transport properties between heparin and other
      macromolecules suggest that distribution and the optimal aspect of delivery will
      depend just as much on the physicochemical properties of the drug as the state of
      the blood vessel wall.

PMID- 7586228
TI  - Cloned human inward rectifier K+ channel as a target for class III
      methanesulfonanilides.
AB  - Methanesulfonanilide derivatives such as dofetilide are members of the widely
      used Class III group of cardiac antiarrhythmic drugs. A methanesulfonanilide
      sensitive cardiac current has been identified as IKr, the rapidly activating
      component of the repolarizing outward cardiac K+ current, IK. IKr may be encoded
      by the human ether-related gene (hERG), which belongs to the family of voltage
      dependent K+ (Kv) channels having six putative transmembrane segments. The hERG
      also expresses an inwardly rectifying, methanesulfonanilide-sensitive K+ current.
      Here we show that hIRK, a member of the two-transmembrane-segment family of
      inward K+ rectifiers that we have cloned from human heart, is a target for
      dofetilide. hIRK currents, expressed heterologously in Xenopus oocytes, are
      blocked by dofetilide at submicromolar concentrations (IC50 = 533 nmol/L at 40 mV
      and 20 degrees C). The drug has no significant blocking effect on the human
      cardiac Kv channels hKv1.2, hKv1.4, hKv1.5, or hKv2.1. The block is voltage
      dependent, use dependent, and shortens open times in a manner consistent with
      open-channel block. While steady state block is strongest at depolarized
      potentials, recovery from block is very slow even at hyperpolarized potentials
      (tau = 1.17 seconds at -80 mV). Thus, block of hIRK may persist during diastole
      and might thereby affect cardiac excitability.

PMID- 7586230
TI  - Effects of pacing on stationary reentrant activity. Theoretical and experimental
      study.
AB  - It is well known that electrical pacing may either terminate or change the rate
      and/or ECG appearance of reentrant ventricular tachycardia. However, the dynamics
      of interaction of reentrant waves with waves initiated by external pacing are
      poorly understood. Prevailing concepts are based on simplistic models in which
      propagation occurs in one-dimensional rings of cardiac tissue. Since reentrant
      activation in the ventricles occurs in two or three dimensions, such concepts
      might be insufficient to explain the mechanisms of pacing-induced effects. We
      used numerical and biological models of cardiac excitation to explore the
      phenomena, which may take place as a result of electrical pacing during
      functionally determined reentry. Computer simulations of a two-dimensional array
      of electrically coupled FitzHugh-Nagumo cells were used to predict the response
      patterns expected from thin slices of sheep ventricular epicardial muscle, in
      which self-sustaining reentrant activity in the form of spiral waves was
      consistently initiated by premature stimulation and monitored by means of video
      mapping techniques. The results show that depending on their timing and shape,
      externally induced waves may collide with the self-sustaining spiral and result
      in one of three possible outcomes: (1) direct annihilation of the spiral, (2)
      multiplication of the spiral, or (3) shift of the spiral center (ie, core).
      Multiplication and shift of the spiral core were attended by changes in rate and
      morphology of the arrhythmia as seen by "pseudo-ECGs." Furthermore, delayed
      termination (ie, termination of the activity one to three cycles after the
      stimulus) occurred after both multiplication and shift of the spiral center. Both
      numerical predictions and experimental results support the hypothesis that
      whether a pacing stimulus will terminate a reentrant arrhythmia or modify its ECG
      appearance depends on whether the interactions between the externally induced
      wave and the spiral wave result in the de novo formation of one or more
      "wavebreaks." The final outcome depends on the stimulus parameters (ie, position
      and size of the electrodes and timing of the stimulus) as well as on the position
      of the newly formed wavebreak(s) in relation to that of the original wave.

PMID- 7586231
TI  - Diminished Ca2+ and Ba2+ currents in myocytes surviving in the epicardial border
      zone of the 5-day infarcted canine heart.
AB  - Ventricular arrhythmias frequently occur in patients suffering from ischemic
      heart disease. In a canine model developed to understand the
      pathoelectrophysiological mechanisms of the ischemia-related arrhythmias,
      electrical stimulation can initiate and terminate reentrant ventricular
      tachyarrhythmias, which arise in surviving subepicardial muscle fibers
      (epicardial border zone [EBZ] fibers) of the left ventricle 5 days after coronary
      artery occlusion. Both the structural and electrical changes occurring in the EBZ
      provide the important substrate for generation of reentrant ventricular
      tachyarrhythmias. In this study, we tested the hypothesis that abnormalities
      exist in the electrophysiological properties of macroscopic Ca2+ currents in
      myocytes isolated from the EBZ of the 5-day infarcted canine heart (IZs). We
      recorded the T-type (ICa,T) and L-type (ICa,L) Ca2+ currents by using the whole
      cell voltage-clamp technique with either Ca2+ or Ba2+ (5 mmol/L) as the charge
      carrier and under experimental conditions (Na(+)- and K(+)-free solutions, 10
      mmol/L intracellular EGTA) that eliminated contamination by other currents. When
      Ca2+ served as the charge carrier, the density of peak ICa,T in IZs (0.89 +/- 0.5
      pA/pF, n = 28) was similar to that in myocytes from normal noninfarcted hearts
      (NZs) (1.1 +/- 0.5 pA/pF, n = 32). Although no changes existed in the properties
      of ICa,T, dramatic changes occurred in the density and function of ICa.L in IZs
      compared with NZs. Density of peak ICa,L at a holding potential of -40 mV (8
      second clamp-step interval) was significantly reduced in IZs (4.6 +/- 1.5 pA/pF,
      n = 40) compared with NZs (7.2 +/- 1.6 pA/pF, n = 53). The reduction in peak
      ICa,L density was not attributable to altered steady state inactivation relations
      or a delay in recovery of ICa,L from inactivation. The time course of decay of
      peak ICa,: was described by a biexponential function in both cell types, with the
      fast and slow time constants (tau 1 and tau 2, respectively) of decay being
      significantly faster in IZs (tau 1 12.3 +/- 3.6 ms; tau 2, 55.1 +/- 31.1 ms) than
      in NZs (tau 1, 16.1 +/- 4.1 ms; tau 2, 85.2 +/- 51.7 ms). In addition, rapid
      clamp stimulation (at 1-s intervals) of cells produced a larger frequency
      dependent decrease of peak ICa,L density in IZs than NZs, suggesting that at more
      physiologically relevant rates, little ICA.L may be activated. Finally, a
      significant reduction and acceleration of decay of the ICa,L persisted even when
      Ca2+ was substituted by equimolar Ba2+ as the charge carrier.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7586229
TI  - Selectivity of connexin-specific gap junctions does not correlate with channel
      conductance.
AB  - Connexins form a variety of gap junction channels that vary in their
      developmental and tissue-specific levels of expression, modulation of gating by
      transjunctional voltage and posttranslational modification, and unitary channel
      conductance (gamma j). Despite a 10-fold variation in gamma j, whether connexin
      specific channels possess distinct ionic and molecular permeabilities is
      presently unknown. A major assumption of the conventional model for a gap
      junction channel pore is that gamma j is determined primarily by pore diameter.
      Hence, molecular size permeability limits should increase and ionic selectivity
      should decrease with increasing channel gamma j (and pore diameter). Equimolar
      ion substitution of 120 mmol/L KCl for potassium glutamate was used to determine
      the unitary conductance ratios for rat connexin40 and connexin43, chicken
      connexin43 and connexin45, and human connexin37 channels functionally expressed
      in communication-deficient mouse neuroblastoma (N2A) cells. Comparison of
      experimental and predicted conductance ratios based on the aqueous mobilities of
      all ions according to the Goldman-Hodgkin-Katz current equation was used to
      determine relative anion-to-cation permeability ratios. Direct correlation of
      junctional conductance with dye transfer of two fluorescein-derivatives (2 mmol/L
      6-carboxyfluorescein or 2',7'-dichlorofluorescein) was also performed. Both
      approaches revealed a range of selectivities and permeabilities for all five
      different connexins that was independent of channel conductance. These results
      are not consistent with the conventional simple aqueous pore model of a gap
      junction channel and suggest a new model for connexin channel conductance and
      permselectivity based on electrostatic interactions. Divergent conductance and
      permeability properties are features of other classes of ion channels (eg, Na+
      and K+ channels), implying similar mechanisms for selectivity.

PMID- 7586232
TI  - pHi regulation in myocardium of the spontaneously hypertensive rat. Compensated
      enhanced activity of the Na(+)-H+ exchanger.
AB  - To elucidate the mechanisms controlling pHi in myocardium of the spontaneously
      hypertensive rat (SHR), experiments were performed in papillary muscles
      (isometrically contracting at 0.2 Hz) from SHR and age-matched normotensive
      Wistar-Kyoto (WKY) rats loaded with the pH-sensitive fluorescent probe BCECF-AM.
      An enhanced activity of the Na(+)-H+ exchanger was detected in the hypertrophic
      myocardium of SHR. This conclusion was based on the following: (1) The myocardial
      pHi was more alkaline in SHR (7.23 +/- 0.03) than in WKY rats (7.10 +/- 0.03) (P
      < .05) in HEPES buffer. (2) SITS (0.1 mmol/L in HEPES buffer) did not alter pHi
      in the SHR (pHi 7.26 +/- 0.03 and 7.28 +/- 0.03 before and after SITS,
      respectively). (3) The fall in pHi observed after 20 minutes of Na(+)-H+
      exchanger inhibition [5 mumol/L 5-(N-ethyl-N-isopropyl)amiloride (EIPA)] was
      greater in SHR (-0.16 +/- 0.01) than in WKY rats (-0.09 +/- 0.02, P < 0.05). (4)
      The velocity of pHi recovery from an intracellular acid load was faster in SHR
      than in WKY rats (0.068 +/- 0.02 versus 0.014 +/- 0.002 pH units/min at pHi 6.99,
      P < .05). (5) After EIPA inhibition, the rate of pHi recovery from the same acid
      load decreased to a similar value in both rat strains (0.0032 +/- 0.002 pH
      units/min in SHR and 0.0032 +/- 0.002 pH units/min in WKY rats). Under the more
      physiological HCO3(-)-CO2 buffer, no significant difference in steady state
      myocardial pHi was detected between rat strains (7.15 +/- 0.03 in SHR and 7.11 +/
      0.05 in WKY rats).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586233
TI  - Tracer oxygen distribution is barrier-limited in the cerebral microcirculation.
AB  - The kinetics of tracer oxygen distribution in the brain microcirculation of the
      awake dog were investigated with the multiple indicator dilution technique. A
      bolus containing 51Cr-labeled red blood cells, previously totally desaturated and
      then resaturated with [18O]2 (oxygen), 125I-albumin, 22Na, and [3H]water, was
      injected into the carotid artery, and serial anaerobic blood samples were
      collected from the sagittal sinus over the next 30 seconds. The outflow recovery
      curves were analyzed with a distributed-in-space two-barrier model for water and
      a one-barrier model for oxygen. The analysis provided an estimate of flow per
      gram brain weight as well as estimates for the tracer water and oxygen rate
      constants for blood-to-brain exchange and tracer oxygen parenchymal
      sequestration. Flow to tissue was found to vary between different animals, in
      concert with parallel changes in oxygen consumption. The 18O2 outflow curves
      showed an early peak, coincident with and more than half the magnitude of its
      vascular reference curve (labeled red blood cells), whereas the [3H]water curve
      increased abruptly to a low-in-magnitude curve at low flow values and to a small
      early peak at high flow values. Analysis indicates that the transfers of both
      18O2 and [3H]water indicators from blood to brain are barrier-limited, with the
      former highly so because of the large red blood cell capacity for oxygen, and
      that the proportion of the tracer oxygen returning to the circulation from tissue
      is a small fraction of the total tracer emerging at the outflow.

PMID- 7586234
TI  - Fractal 15O-labeled water washout from the heart.
AB  - To characterize the washout of water from the heart, we used a flow-limited (not
      diffusion- or permeability-limited) marker for blood-tissue exchange, namely,
      tracer-labeled water. Experiments were performed by injecting 15O-labeled water
      into the inflow to isolated blood-perfused rabbit hearts and by recording the
      tracer content in the heart and in the outflow simultaneously for up to 5
      minutes. The data exhibit a particular combination of power law forms: (1) The
      downslopes of the residue and outflow curves were both power law functions, with
      the residue diminishing as t-alpha and the outflow as t-alpha-1, where alpha is
      interpreted to be the dimensionless exponent of a fractal power law relation
      characterizing the self-similarity inherent in each curve. (2) The fractional
      escape rate, given by the outflow curve divided by the residue curve, diminished
      almost exactly as t-1. In 18 sets of curves, alpha averaged 2.21 +/- 0.27. These
      results lead to an improved method for extrapolating the downslopes of indicator
      dilution curves to estimate their areas and therefore the blood flows. The
      evidence also points strongly to the conclusions that myocardial water washout is
      a fractal process and that stirred tank models are inappropriate for the heart.

PMID- 7586235
TI  - Cutaneous active vasodilation in humans is mediated by cholinergic nerve
      cotransmission.
AB  - During heat stress, increases in blood flow in nonglabrous skin in humans are
      mediated through active vasodilation by an unknown neurotransmitter mechanism. To
      investigate this mechanism, a three-part study was performed to determine the
      following: (1) Is muscarinic receptor activation necessary for active cutaneous
      vasodilation? We iontophoretically applied atropine to a small area of forearm
      skin. At that site and an untreated control site, we measured the vasomotor
      (laser-Doppler blood flow [LDF]) and sudomotor (relative humidity) responses to
      whole-body heat stress. Blood pressure was monitored. Cutaneous vascular
      conductance (CVC) was calculated (LDF divided by mean arterial pressure).
      Sweating was blocked at treated sites only. CVC rose at both sites (P < .05 at
      each site); thus, cutaneous active vasodilation is not effected through
      muscarinic receptors. (2) Are nonmuscarinic cholinergic receptors present on
      cutaneous arterioles? Acetylcholine (ACh) was iontophoretically applied to
      forearm skin at sites pretreated by atropine iontophoresis and at untreated
      sites. ACh increased CVC at untreated sites (P < .05) but not at atropinized
      sites. Thus, the only functional cholinergic receptors on cutaneous vessels are
      muscarinic. (3) Does cutaneous active vasodilation involve cholinergic nerve
      cotransmission? Botulinum toxin was injected intradermally in the forearm to
      block release of ACh and any coreleased neurotransmitters. Heat stress was
      performed as in part 1 of the study. At treated sites, CVC and relative humidity
      remained at baseline levels during heat stress (P > .05). Active vasodilator and
      sudomotor responses to heat stress were abolished by botulinum toxin. We conclude
      that cholinergic nerve activation mediates cutaneous active vasodilation through
      release of an unknown cotransmitter, not through ACh.

PMID- 7586236
TI  - Transmembrane voltage changes during unipolar stimulation of rabbit ventricle.
AB  - This study tested the prediction of bidomain models that unipolar stimulation of
      anisotropic myocardium produces transmembrane voltage changes (delta VmS) of
      opposite signs away from the electrode on perpendicular axes. Stimulation with a
      strength of 0.1 to 40 mA was applied from a point electrode on the left or right
      ventricle of isolated perfused rabbit hearts at 37 degrees C to 38 degrees C
      stained with the potentiometric dye di-4-ANEPPS. A laser scanner system recorded
      Vm-sensitive fluorescence at 63 spots in an 8 x 8-mm region around the electrode.
      Cathodal stimulation in the refractory period produced regions of -delta Vm 1 to
      5 mm away from the electrode on an axis oriented parallel to the fast propagation
      axis to within 1.8 +/- 11 degrees (P > or = .7 for difference versus zero, n =
      7). Recording spots in these regions underwent + delta Vm when anodal stimulation
      was used. At recording spots on the slow propagation axis, cathodal stimulation
      produced + delta Vm and anodal stimulation produced -delta Vm. During diastolic
      stimulation, early excitation occurred near the electrode for cathodal
      stimulation or on the fast propagation axis as fas as 2.8 +/- 1 mm away from the
      electrode for anodal stimulation. A "dog-bone" region of + delta Vm that included
      tissue near and away from the electrode on the slow propagation axis occurred
      when cathodal stimulation was given in diastole. Regions of + delta Vm occurred
      away from the electrode on the fast propagation axis when anodal stimulation was
      given in diastole. Thus, delta Vm differs in regions along and across myocardial
      fibers, indicating that delta Vm depends on anisotropic bidomain properties.
      Sites of early excitation are those where + delta Vm occurs, indicating that
      membrane channel excitation depends on the distribution of delta Vm.

PMID- 7586238
TI  - Anti-minK antisense decreases the amplitude of the rapidly activating cardiac
      delayed rectifier K+ current.
AB  - The rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs,
      respectively), which have different physiological properties have been identified
      in cardiac cells from several species, including humans. Although expression of
      the minimal K+ channel protein (minK) cDNA in some systems results in a current
      resembling IKs, the role of this gene product in channel function remains
      controversial. In atrial tumor myocytes (AT-1 cells), no IKs is recorded, but
      minK mRNA is detected, raising the possibility that expression of the minK gene
      serves an as-yet-unidentified function. In these experiments, AT-1 cells were
      exposed to antisense oligonucleotides targeting the 5' translation start site of
      the minK cDNA cloned from an AT-1 library. Cell size, IKr, and L-type and T-type
      Ca2+ currents were measured 24 to 48 hours after exposure and compared with data
      in cells exposed to the corresponding sense oligonucleotide or grown in medium
      only. Antisense oligonucleotide significantly reduced IKr compared with sense and
      medium-only control cells in 0 of 2 experiments (n = 3 to 6 cells per treatment
      in each experiment) at 50 nmol/L, 1 of 2 at 250 nmol/L, 6 of 6 at 1000 nmol/L,
      and 2 of 2 at 10,000 nmol/L. At 1000 nmol/L, maximum tail current in antisense
      exposed cells was 2.5 +/- 0.1 pA/pF (mean +/- SEM, n = 28, 6 separate
      experiment), 6.6 +/- 0.4 pA/pF in sense-exposed cells (n = 27), 5.4 +/- 0.6 pA/pF
      in medium-only cells (n = 21), and 5.8 +/- 0.7 pA/pF in cells exposed to a random
      oligonucleotide (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586237
TI  - Renal effects of high-dose natriuretic peptide receptor blockade in rats with
      congestive heart failure.
AB  - Previous studies suggest that elevated plasma atrial natriuretic peptide (ANP)
      levels participate in regulating renal excretory function in rats with congestive
      heart failure (CHF). To define the role of natriuretic peptides (NPs) in the
      regulation of renal function in CHF, the renal responses to HS-142-1 (HS), a
      potent NP receptor antagonist, were studied in anesthetized rats subjected to
      coronary ligation that developed left ventricular infarction and CHF or in sham
      operated (SO) control rats. Plasma ANP levels averaged > 14-fold higher in rats
      with CHF than in SO rats. In response to HS (20 mg/kg IV bolus), both mean
      arterial pressure and renal vascular resistance increased in rats with CHF but
      not in SO rats; glomerular filtration rate (GFR, 1.26 +/- 0.04 versus 0.76 +/-
      0.11 mL/min) and renal plasma flow rate (RPF, 3.52 +/- 0.27 versus 2.70 +/- 0.32
      mL/min) were significantly reduced in rats with CHF; and in SO rats, GFR (1.26 +/
      0.06 versus 1.20 +/- 0.07 mL/min) and RPF (3.98 +/- 0.21 versus 3.99 +/- 0.18
      mL/min) were not significantly affected by HS. The sodium excretion rate (0.18 +/
      0.04 to 0.06 +/- 0.01 muEq/min) and fractional sodium excretion (0.01 +/- 0.02%
      to 0.04 +/- 0.01%) also fell markedly after HS administration in rats with CHF,
      but these parameters were unchanged in SO rats. These data indicate that NPs play
      a critical role in maintaining renal hemodynamic function and inhibiting tubule
      sodium reabsorption in rats with CHF, thus opposing sodium retention and
      preserving sodium balance in this model.

PMID- 7586239
TI  - Using public policy to fight heart disease and stroke. A 21st century approach.

PMID- 7586240
TI  - Congenital long QT syndromes. Toward molecular dissection of arrhythmia
      substrates.

PMID- 7586241
TI  - There may be more to myocardial viability than meets the eye.

PMID- 7586242
TI  - More on thrombolysis and hemorrhagic stroke.

PMID- 7586243
TI  - Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme
      is associated with coronary artery disease and myocardial infarction in low-risk
      patients.
AB  - BACKGROUND: An insertion/deletion (I/D) polymorphism of the angiotensin I
      converting enzyme (ACE) gene has been postulated to be associated with an
      increased risk of coronary artery disease (CAD) and myocardial infarction (MI).
      METHODS AND RESULTS: In the present study, the effects of I/D gene polymorphism
      and of ACE activity on CAD and MI were investigated in 920 individuals who
      underwent coronary angiography for diagnostic purposes. In the total population
      and in all CAD and MI groups, a strong association was observed between the gene
      polymorphism and ACE activities; DD genotypes had approximately twofold higher
      ACE activities than II genotypes. Although classic risk and protective factors of
      CAD and MI were identified, associations of ACE genotype and of ACE activity to
      CAD and MI were not detected in the total population. Among subjects defined to
      be at lower risk of MI by low body mass index and low cigarette consumption,
      however, an association of the DD genotype with MI was found. Exclusion of
      individuals with triglyceride levels > 140 mg/dL and cholesterol levels > 180
      mg/dL revealed an association of the DD genotype with CAD. An association of the
      ACE activity with CAD or MI could not be demonstrated in any of the low-risk
      populations. CONCLUSIONS: Increased ACE activity obviously is not a risk factor
      of CAD or MI. The importance of the deletion polymorphism for the development of
      CAD and MI may be restricted to individuals without classic risk factors.

PMID- 7586244
TI  - Factor V Leiden and risks of recurrent idiopathic venous thromboembolism.
AB  - BACKGROUND: Whether Leiden mutation in the gene coding for coagulation factor V
      is associated with recurrent idiopathic venous thromboembolism (VTE) is unknown,
      but such data are necessary to evaluate the merits of genetic screening in
      secondary prevention of thromboembolic disease. METHODS AND RESULTS: Among 14,916
      apparently healthy men who provided DNA samples and were followed in the
      Physicians' Health Study through August 1994, 77 suffered an idiopathic VTE.
      These 77 men were followed for an additional average period of 68.3 months,
      during which time 11 (14.3%) suffered a recurrent idiopathic VTE. Factor V Leiden
      status was assessed in these men, and incidence rates of recurrence were
      calculated by genotype. All recurrent events occurred after cessation of
      anticoagulation. Seven recurrences occurred among 63 genetically unaffected
      subjects (11.1%; incidence rate, 1.82 per 100 person-years), while four occurred
      among those 14 heterozygous for factor V Leiden (28.6%; incidence rate, 7.46 per
      100 person-years). Thus, factor V Leiden was associated with a fourfold to
      fivefold increase in risk of recurrent VTE (crude relative risk, 4.1; P = .04;
      age- and smoking-adjusted relative risk, 4.7; P = .047). There was no difference
      in mean time between index and recurrent events by genotype. Among heterozygous
      men, 76% of recurrent events were attributable to mutation. CONCLUSIONS: In
      prospective evaluation of 77 men with a history of idiopathic VTE, factor V
      Leiden was associated with a fourfold to fivefold increased risk of recurrent
      thrombosis. These data raise the possibility that patients with VTE affected by
      factor V Leiden may require more prolonged anticoagulation to prevent recurrent
      disease compared with those without mutation.

PMID- 7586245
TI  - Molecular analysis of nondisjunction in Down syndrome patients with and without
      atrioventricular septal defects.
AB  - BACKGROUND: Congenital heart disease is common in Down syndrome patients, with
      atrioventricular septal defects accounting for a majority of the abnormalities.
      The molecular mechanisms of meiotic nondisjunction resulting in Down syndrome
      were studied for associations with the presence of atrioventricular septal
      defects. METHODS AND RESULTS: Twenty highly polymorphic chromosome 21
      microsatellite markers were used to genotype two groups of patients (group 1:
      Down syndrome with atrioventricular septal defects, n = 43; and group 2: Down
      syndrome without cardiac defects, n = 51) to determine (1) the parental origin of
      the extra chromosome, (2) the stage of meiotic nondisjunction resulting in the
      trisomy, (3) the presence or absence of disomic homozygosity or heterozygosity,
      and (4) the degree of recombination in the nondisjoined chromosomes. The parental
      origin of the nondisjoined chromosome was maternal in 86.2% of the families, with
      no significant differences between groups. The most centromeric marker was
      nonreduced, indicating a meiosis I nondisjunction in 76.5% of maternally derived
      trisomies, and reduced, indicating a meiosis II nondisjunction in 76.9% of
      paternally derived trisomies, with no significant differences between groups.
      There were no significant differences in the proportion of reduced markers at any
      locus between groups. The distribution of the number of crossovers was
      significantly different between groups (chi 2 = 14.12, P < .001), with less
      recombination observed in group 1. CONCLUSIONS: In Down syndrome patients, no
      association was found between the presence of an atrioventricular septal defect
      and the parent of origin, stage of meiotic nondisjunction, or disomic
      homozygosity or heterozygosity. A significant association was found between the
      presence of an atrioventricular septal defect and reduced frequency of
      recombination.

PMID- 7586247
TI  - Prolonged antithrombin activity of low-molecular-weight heparins. Clinical
      implications for the treatment of thromboembolic diseases.
AB  - BACKGROUND: The mechanism for the efficacy of once- or twice-daily subcutaneous
      injections of low-molecular-weight heparins (LMWHs) for the treatment of venous
      thromboembolism has been difficult to explain. The confusion exists because the
      observation from experimental studies that the antithrombin activity of LMWHs is
      necessary for their antithrombotic effect is inconsistent with the reported short
      half-life of the antithrombin activity of LMWHs. Previous pharmacokinetic studies
      were performed with lower doses of LMWHs than have been used in contemporary
      trials, and antithrombin activity was assessed with the barely sensitive
      chromogenic assay. METHODS AND RESULTS: We performed a pharmacokinetic study to
      compare the relative half-lives of prophylactic and therapeutic doses of LMWHs
      assessing antithrombin activity with both the chromogenic and a more sensitive
      assay (plasma thrombin neutralization assay). An eight-way cross-over randomized
      study in healthy volunteers was performed. Enoxaparin (20 and 40 mg and 1 and 2
      mg/kg) and nadroparin (7500 and 10,000 ICU and 225 and 450 ICU/kg) were
      administered subcutaneously. The maximal peak activity for aPTT ratio was 1.7. A
      dose-dependent peak activity was found for both antifactor Xa and antithrombin
      activities. Disappearance time of these activities after the highest dose of both
      LMWHs was longer than 16 hours. Overall mean antifactor Xa activity half-life was
      4.6 hours. Overall mean antithrombin activity half-life was longer than 4 hours.
      CONCLUSIONS: Our results provide an explanation for the effectiveness of LMWHs
      administered either once or twice daily. High and sustained plasma antithrombin
      activity is achieved when LMWHs are administered in therapeutic doses used in
      contemporary trials with only a moderate prolongation of the aPTT.

PMID- 7586246
TI  - Stroke after thrombolysis. Mortality and functional outcomes in the GUSTO-I
      trial. Global Use of Strategies to Open Occluded Coronary Arteries.
AB  - BACKGROUND: Stroke is the most feared complication of thrombolysis for acute
      myocardial infarction because of the resulting mortality and disability. We
      analyzed the incidence, timing, and outcomes of stroke in an international trial.
      METHODS AND RESULTS: Patients were randomly assigned to one of four thrombolytic
      strategies. Neurological events were confirmed clinically and anatomically and
      were adjudicated by a blinded committee. Stroke survivors, categorized by
      residual deficit and disability, assessed their quality of life with a time trade
      off technique. Multivariable regression identified patient characteristics
      associated with intracranial hemorrhage. Over-all, 1.4% of the patients had a
      stroke (93% anatomic documentation). The risk ranged from 1.19% with
      streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic
      therapy (P = .007). Primary intracranial hemorrhage rates ranged from 0.46% with
      streptokinase/subcutaneous heparin to 0.88% with combination therapy (P < .001).
      Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling,
      with no significant treatment-related differences. Stroke subtype affected
      prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were
      disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions.
      Patients with moderate or severe residual deficits showed significantly decreased
      quality of life. Advanced age, lower weight, prior cerebrovascular disease or
      hypertension, systolic and diastolic blood pressures, randomization to tissue
      plasminogen activator, and an interaction between age and hypertension were
      significant predictors of intracranial hemorrhage. CONCLUSIONS: Stroke remains a
      rare but catastrophic complication of thrombolysis. Additional studies should
      assess the net clinical benefit of thrombolysis in high-risk subgroups,
      particularly the elderly and patients with prior cerebrovascular events.

PMID- 7586248
TI  - Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent
      reversible risk factors for coronary artery disease.
AB  - BACKGROUND: High plasma homocysteine is associated with premature coronary artery
      disease in men, but the threshold concentration defining this risk and its
      importance in women and the elderly are unknown. Furthermore, although low B
      vitamin status increases homocysteine, the link between these vitamins and
      coronary disease is unclear. METHODS AND RESULTS: We compared 304 patients with
      coronary disease with 231 control subjects. Risk factors and concentrations of
      plasma homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate were
      documented. A homocysteine concentration of 14 mumol/L conferred an odds ratio of
      coronary disease of 4.8 (P < .001), and 5-mumol/L increments across the range of
      homocysteine conferred an odds ratio of 2.4 (P < .001). Odds ratios of 3.5 in
      women and of 2.9 in those 65 years or older were seen (P < .05). Homocysteine
      correlated negatively with all vitamins. Low pyridoxal 5'-phosphate (< 20 nmol/L)
      was seen in 10% of patients but in only 2% of control subjects (P < .01),
      yielding an odds ratio of coronary disease adjusted for all risk factors,
      including high homocysteine, of 4.3 (P < .05). CONCLUSIONS: Within the range
      currently considered to be normal, the risk for coronary disease rises with
      increasing plasma homocysteine regardless of age and sex, with no threshold
      effect. In addition to a link with homocysteine, low pyridoxal-5'-phosphate
      confers an independent risk for coronary artery disease.

PMID- 7586249
TI  - A comparison of the costs of and quality of life after coronary angioplasty or
      coronary surgery for multivessel coronary artery disease. Results from the Emory
      Angioplasty Versus Surgery Trial (EAST).
AB  - BACKGROUND: The Emory Angioplasty Versus Surgery Trial (EAST) is a randomized
      trial that compares, by intention to treat, the clinical outcome and costs of
      percutaneous transluminal coronary angioplasty (PTCA) and coronary surgery for
      multivessel coronary artery disease. METHODS AND RESULTS: The primary end point
      was a composite of death, Q-wave myocardial infarction, and a large reversible
      thallium defect at 3 years. Multiple measures of quality of life also were made.
      Charges were assessed from the hospital UB-82 bills; professional charges were
      assessed from the Emory Clinic. Hospital charges were reduced to cost through
      step-down accounting methods. All costs and charges were deflated to 1987
      dollars. Costs were assessed for the initial hospitalization and the cumulative
      costs of the initial hospitalization and additional revascularization procedures
      for up to 3 years. There was no difference in mortality or the primary end point.
      Mean initial hospital charges were $12,654 for the PTCA group and $20,214 for the
      surgery group (P < .0001). Professional charges were 4538 for PTCA and $9426 for
      surgery (P < .0001). Three-year hospital charges were $19,047 for PTCA and
      $21,174 for coronary surgery (P < .0001). Three-year professional charges were
      $6412 for PTCA and $9861 for surgery (P < .0001). Three-year total charges were
      $25,458 for PTCA and $31,033 for surgery (P < .0001). Total 3-year costs were
      $23,734 for PTCA and $25,310 for coronary surgery (P < .0001). There were more
      hospitalizations for angina and more antianginal medications used in the PTCA
      group, which would further narrow the differences in cost. CONCLUSIONS: There was
      no difference in the primary end point or its components at 3 years. Although the
      primary procedural costs of coronary surgery are more than for coronary
      angioplasty, this cost advantage is largely, although probably not completely,
      lost by 3 years because of more frequent additional procedures and other resource
      consumption after a first revascularization by PTCA.

PMID- 7586253
TI  - Comparison of myocardial contrast echocardiography and low-dose dobutamine stress
      echocardiography in predicting recovery of left ventricular function after
      coronary revascularization in chronic ischemic heart disease.
AB  - BACKGROUND: Dobutamine stress echocardiography (DSE) and myocardial contrast
      echocardiography (MCE) can predict recovery of left ventricular function after
      myocardial infarction. DSE also has been shown to predict left ventricular
      functional recovery after revascularization in chronic ischemic heart disease,
      whereas MCE has not been evaluated in such patients. This study was performed to
      compare DSE and MCE in the prediction of left ventricular functional recovery
      after revascularization in patients with chronic ischemic heart disease. METHODS
      AND RESULTS: MCE and DSE were performed in 35 patients with chronic coronary
      artery disease and significant wall motion abnormalities (mean ejection fraction,
      0.36 +/- 0.09). Regional wall motion was scored by use of a 16-segment model
      wherein 1 = normal or hyperkinetic, 2 = hypokinetic, 3 = akinetic, and 4 =
      dyskinetic. Each segment was evaluated for contractile reserve by DSE and
      perfusion by MCE. Revascularization (coronary artery bypass graft [n = 13] and
      percutaneous transluminal coronary angioplasty [n = 10]) was successful in 23
      patients. Follow-up echocardiograms were done to assess wall motion 30 to 60 days
      later. In 238 segments with resting wall motion abnormalities, perfusion was more
      likely to present than contractile reserve (97% versus 91%, P < .02).
      Revascularization resulted in functional recovery in 77 of 95 hypokinetic
      segments (81%) but only 18 of 57 akinetic segments (32%, P < .0001). DSE and MCE
      were not significantly different in predicting functional recovery of hypokinetic
      segments. In akinetic segments, DSE and MCE had similar sensitivities (89% versus
      94%, respectively) and negative predictive values (93% and 97%, respectively) in
      predicting functional recovery. However, DSE had a higher specificity (92% versus
      67%, P < .02) and positive predictive value (85% versus 55%, P < .02) than MCE in
      predicting functional recovery. CONCLUSIONS: Both contractile reserve by DSE and
      perfusion by MCE are predictive of functional recovery in hypokinetic segments
      after coronary revascularization in patients with chronic coronary
      revascularization in patients with chronic coronary artery disease. In akinetic
      segments, myocardial perfusion by MCE may exist in segments that do not recover
      contractile function after revascularization. Thus, contractile reserve during
      low-dose dobutamine infusion is a better predictor of functional recovery after
      revascularization in akinetic segments than perfusion.

PMID- 7586252
TI  - N-acetylcysteine in combination with nitroglycerin and streptokinase for the
      treatment of evolving acute myocardial infarction. Safety and biochemical
      effects.
AB  - BACKGROUND: N-acetylcysteine (NAC) has been shown to potentiate the effects of
      nitroglycerin (NTG) and to have antioxidant activity. This is the first study to
      assess the safety and effect of NAC in the treatment of evolving acute myocardial
      infarction (AMI). METHODS AND RESULTS: Patients with AMI received either 15 g NAC
      infused over 24 hours (n = 20) or no NAC (n = 7), combined with intravenous NTG
      and streptokinase. Peripheral venous plasma malondialdehyde (MDA), reduced (GSH)
      and oxidized (GSSG) glutathione concentrations, and rate of reperfusion (using
      continuous ST-segment analysis) were measured. Cardiac catheterization was
      performed between days 2 and 5. No significant adverse events occurred. Less
      oxidative stress occurred in patients treated with NAC than in patients not
      receiving NAC (GSH to GSSG ratio 44 +/- 25 versus 19 +/- 13 at 4 hours, P < .05).
      NAC concentration (mean 172 +/- 79 mumol/L at 4 hours) was correlated to GSH
      concentration (P = .006). MDA concentrations were lower (P = .001) over the first
      8 hours of treatment with NAC. There was a trend toward more rapid reperfusion
      (median 58 minutes, 95% confidence interval [CI] 48 to 98 minutes versus median
      95 minutes, 95% CI 59 to 106 minutes; P = .17) and better preservation of left
      ventricular function (cardiac index 3.4 +/- 0.8 versus 2.6 +/- 0.27 L.min.m2, P =
      .009) with NAC treatment. CONCLUSIONS: NAC in combination with NTG and
      streptokinase appeared to be safe for the treatment of evolving AMI and was
      associated with significantly less oxidative stress, a trend toward more rapid
      reperfusion, and better preservation of left ventricular function.

PMID- 7586251
TI  - Discrimination between myocardial and skeletal muscle injury by assessment of the
      plasma ratio of myoglobin over fatty acid-binding protein.
AB  - BACKGROUND: Myoglobin and fatty acid-binding protein (FABP) each are useful as
      early biochemical markers of muscle injury. We studied whether the ratio of
      myoglobin over FABP in plasma can be used to distinguish myocardial from skeletal
      muscle injury. METHODS AND RESULTS: Myoglobin and FABP were assayed
      immunochemically in tissue samples of human heart and skeletal muscle and in
      serial plasma samples from 22 patients with acute myocardial infarction (AMI),
      from 9 patients undergoing aortic surgery (causing injury of skeletal muscles),
      and from 10 patients undergoing cardiac surgery. In human heart tissue, the
      myoglobin/FABP ratio was 4.5 and in skeletal muscles varied from 21 to 73. After
      AMI, the plasma concentrations of both proteins were elevated between
      approximately 1 and 15 to 20 hours after the onset of symptoms. In this period,
      the myoglobin/FABP ratio was constant both in subgroups of patients receiving and
      those not receiving thrombolytics and amounted to 5.3 +/- 1.2 (SD). In serum from
      aortic surgery patients, both proteins were elevated between 6 and 24 hours after
      surgery; the myoglobin/FABP ratio was 45 +/- 22 (SD), which is significantly
      different from plasma values in AMI patients (P < .001). In patients with cardiac
      surgery, the ratio increased from 11.3 +/- 4.7 to 32.1 +/- 13.6 (SD) during 24
      hours after surgery, indicating more rapid release of protein from injured
      myocardium than from skeletal muscles. CONCLUSIONS: The ratio of the
      concentrations of myoglobin over FABP in plasma from patients with muscle injury
      reflects the ratio found in the affected tissue. Since this ratio is different
      between heart (4.5) and skeletal muscle (20 to 70), its assessment in plasma
      allows the discrimination between myocardial and skeletal muscle injury in
      humans.

PMID- 7586250
TI  - Aspirin in the treatment of acute myocardial infarction in elderly Medicare
      beneficiaries. Patterns of use and outcomes.
AB  - BACKGROUND: Although aspirin is an effective, inexpensive, and safe treatment of
      acute myocardial infarction, the frequency of use of aspirin in actual medical
      practice is not known. Elderly patients, a group with low rates of utilization of
      effective therapies such as thrombolytic therapy, also may be at risk of not
      receiving aspirin for acute myocardial infarction. To address this issue, we
      sought to determine the current pattern of aspirin use and to assess its
      effectiveness in a large, population-based sample of elderly patients
      hospitalized with acute myocardial infarction. METHODS AND RESULTS: As part of
      the Cooperative Cardiovascular Project Pilot, a Health Care Financing
      Administration initiative to improve quality of care for Medicare beneficiaries,
      we abstracted hospital medical records of Medicare beneficiaries who were
      hospitalized in Alabama, Connecticut, Iowa, or Wisconsin from June 1992 through
      February 1993. Among the 10,018 patients > or = 65 years old who had no absolute
      contraindications to aspirin, 6140 patients (61%) received aspirin within the
      first 2 days of hospitalization. Patients who were older, had more comorbidity,
      presented without chest pain, and had high-risk characteristics such as heart
      failure and shock were less likely to receive aspirin. The use of aspirin was
      significantly associated with a lower mortality (OR, 0.78; 95% CI, 0.70 to 0.89)
      after adjustment for potential confounders. CONCLUSIONS: About one third of
      elderly patients with acute myocardial infarction who had no contraindications to
      aspirin therapy did not receive it within the first 2 days of hospitalization.
      The elderly patients with the highest risk of death were the least likely to
      receive aspirin. After adjustment for differences between the treatment groups,
      the use of aspirin was associated with 22% lower odds of 30-day mortality. The
      increased use of aspirin for patients with acute myocardial infarction is an
      excellent opportunity to improve the delivery of care to elderly patients.

PMID- 7586255
TI  - Phenotypic patterns of mononuclear cells in dilated cardiomyopathy.
AB  - BACKGROUND: Immunological factors in the pathogenesis of idiopathic dilated
      cardiomyopathy (IDC) were suggested previously on the basis of the demonstration
      of mononuclear cell infiltrates and autoantibodies against the myocardium. The
      present study investigated whether tissue leukocyte subpopulations isolated from
      hearts with IDC (n = 6) differ in phenotype from those of tissues without IDC (n
      = 7). METHODS AND RESULTS: Leukocytes were quantified as reactive cells per
      square millimeter in perivascular, interstitial, and parenchymal tissue sections.
      Freshly isolated heart-tissue T cells and peripheral-blood T cells from the same
      patients were analyzed by triple staining and flow cytometry to identify T-cell
      subpopulations as well as their states of differentiation (expression of CD45RA
      and Leu-8 versus CD45RO) and activation (IL-2R, IL-7R, very late antigen-1, HLA
      DR). All types of infiltrating cells (T cells, B cells, macrophages,
      granulocytes) are increased in hearts with IDC compared with normal hearts, but
      only CD8+ T cells and macrophages are increased relative to the other leukocyte
      subpopulations. CD45RO+/CD45RA-/Leu-8- cells constitute the majority of heart
      tissue T cells in both normal hearts and hearts with IDC. Strikingly, hearts with
      IDC are infiltrated by eightfold greater numbers of perivascularly located IL
      2R(+)- (26% of all T cells) and CD45RO(+)-activated memory T cells; moreover, in
      contrast to normal heart, approximately 40% of both CD4+ and CD8+ heart-tissue T
      cells express activation markers. CONCLUSIONS: Both normal hearts and hearts with
      IDC are populated by leukocytes. The quantitative increase in IDC, associated
      with a dramatically altered activation status of heart-tissue T cells, suggests a
      direct role of infiltrating leukocytes in the pathogenesis of IDC.

PMID- 7586254
TI  - Development and characterization of a rapid assay for bedside determinations of
      cardiac troponin T.
AB  - BACKGROUND: The appearance of cardiac proteins in blood is the most specific and
      sensitive indicator of acute myocardial cell necrosis. The measurement of cardiac
      markers, however, is time consuming and requires sophisticated equipment. To
      facilitate the biochemical detection for acute myocardial cell necrosis, a whole
      blood rapid assay device for cardiac troponin T detection was developed that
      provides a test result within 20 minutes. METHODS AND RESULTS: Monoclonal
      antibody M7 is labeled with gold particles, and antibody 1B10 is labeled with
      biotin. Both antibodies, as well as buffer substances and detergents, are
      adsorbed onto paper fleeces mounted below an application well. Heparinized blood
      (160 microL) applied to this well solubilizes the dry chemistry reagents. Blood
      cells are separated from plasma via a glass-fiber fleece. The immunocomplexes
      formed are concentrated within the reading zone by binding of the biotin-labeled
      antibody with streptavidine immobilized to the test device. Troponin T bound to
      the test device serves as a control. The detection limit of this assay is 0.18
      microgram/L with a cross-reactivity with skeletal troponin T of 0.5%. In clinical
      analyses involving 25 healthy volunteers, 62 patients with chest pain but without
      myocardial ischemia, 35 patients with acute myocardial infarction, 24 patients
      with minor myocardial cell damage due to radiofrequency ablation, and 35 patients
      with unstable angina, the rapid assay was comparable to the troponin T enzyme
      immunoassay in regard to sensitivity and specificity. CONCLUSIONS: This newly
      developed assay allows accurate, rapid, and convenient diagnosis of acute
      myocardial cell necrosis.

PMID- 7586256
TI  - Exercise capacity in hypertrophic cardiomyopathy. Role of stroke volume
      limitation, heart rate, and diastolic filling characteristics.
AB  - BACKGROUND: We previously showed that exercise capacity in patients with
      hypertrophic cardiomyopathy (HCM) is related to peak exercise cardiac output.
      Cardiac output augmentation during exercise is normally dependent on heart rate
      (HR) response and stroke volume (SV) augmentation by increased left ventricular
      end-diastolic volume and/or increased contractility. We hypothesized that in
      contrast to normal subjects, peak exercise capacity in patients with HCM is
      determined by the diastolic filling characteristics of the left ventricle during
      exercise, which would in turn determine the degree to which SV is augmented, and
      that HR is a relatively unimportant determinant of peak exercise capacity.
      METHODS AND RESULTS: Twenty-three patients with HCM underwent invasive
      hemodynamic evaluation and measurement of maximal oxygen consumption (VO2max)
      during erect treadmill exercise to assess the relative importance of changes in
      HR and SV in determining exercise capacity. Hemodynamic responses to erect and
      supine exercise were compared in 10 of these patients. In a separate group of 46
      patients with HCM, the relation between VO2max and exercise diastolic filling
      indexes was assessed. Peak HR during erect exercise was 92 +/- 8% of predicted
      maximum. VO2max was 29.0 +/- 6.4 mL.kg-1.min-1 and was related significantly to
      peak exercise cardiac index and SV index (r = .71, P < .001 and r = .66, P =
      .001, respectively) but not to peak HR, HR deficit, or resting or peak pulmonary
      capillary wedge pressure. Peak cardiac output during erect exercise was not
      related to peak HR (r = .13, P = NS). When erect and supine exercise were
      compared, peak HR was lower in the supine position (153.3 +/- 19.9 beats per
      minute supine versus 172.0 +/- 17.6 beats per minute erect, P = .003), but peak
      exercise cardiac index was similar (7.9 +/- 2.6 L.min-1.m-2 supine versus 7.5 +/-
      2.8 L.min-1.m-2 erect). Pulmonary capillary wedge pressure was higher at rest in
      the supine versus erect position (15.3 +/- 5.2 versus 8.1 +/- 6.1 mm Hg) but was
      not significantly higher at peak exercise in the supine versus erect position
      (28.5 +/- 8 versus 22.4 +/- 11.6 mm Hg erect, P = NS). In the separate group of
      46 patients with HCM, VO2max was significantly inversely related to time to peak
      filling at peak exercise (r = -.60, P < .0001) but did not correlate with time to
      peak filling at rest, resting ejection fraction, peak filling rate, or peak
      exercise peak filling rate. CONCLUSIONS: SV is the major determinant of peak
      exercise capacity in the erect position in patients with hypertrophic
      cardiomyopathy. This in turn is determined by the exercise left ventricular
      diastolic filling characteristics. HR augmentation does not appear to be a major
      determinant of peak cardiac output in the erect position.

PMID- 7586257
TI  - Demonstrable cardiac reinnervation after human heart transplantation by carotid
      baroreflex modulation of RR interval.
AB  - BACKGROUND: After heart transplantation, respiration-synchronous fluctuations
      (0.18 to 0.35 Hz, high frequency [HF]) in RR interval may result from atrial
      stretch caused by changes in venous return, but slower fluctuations (0.03 to 0.15
      Hz, low frequency [LF]) not due to respiration suggest reinnervation. In normal
      subjects, sinusoidal neck suction selectively stimulates carotid baroreceptors
      and causes reflex oscillations of RR interval. METHODS AND RESULTS: To evaluate
      the presence of reinnervation, we measured the power of RR-LF and RR-HF in 26
      heart transplant recipients and 16 control subjects before and during sinusoidal
      neck suction at 0.1 Hz and 0.20 Hz (similar to but distinct from that of
      controlled respiration, 0.25 Hz) and before and during administration of atropine
      or beta-blocker (esmolol hydrochloride) by spectral analysis. All transplant
      recipients showed small respiratory HF fluctuations. Nonrespiratory LF
      fluctuations were present in 13 of 26 transplant recipients and increased with
      months since transplantation (r = .53, P < .01). HF neck suction induced a 0.20
      Hz component in all 16 control subjects and none of the 26 transplant subjects.
      LF neck suction increased RR-LF (from 0.73 +/- 0.20 to 1.30 +/- 0.26 ln ms2, P <
      .001), similar to but less than in control subjects (from 6.12 +/- 0.21 to 8.27
      +/- 0.21 ln ms2, P < .001). Atropine reduced all fluctuations in control subjects
      and blocked the HF increase caused by 0.20-Hz neck suction but not the LF
      increase during 0.10-Hz stimulation. Neck suction-induced changes in LF
      fluctuations persisted after administration of atropine in transplant recipients
      but were attenuated by esmolol hydrochloride, suggesting sympathetic rather than
      vagal reinnervation. CONCLUSIONS: The presence of baroreceptor-induced RR
      oscillations is evidence of functional, although incomplete, autonomic
      reinnervation.

PMID- 7586259
TI  - Effect of insulin on acetylcholine-induced vasodilation in normotensive subjects
      and patients with essential hypertension.
AB  - BACKGROUND: The present study was designed to directly test the vasodilation
      action of insulin and its relation to endothelium-dependent mechanisms. METHODS
      AND RESULTS: In 18 normotensive subjects and 27 patients with untreated mild to
      moderate essential hypertension, we studied the effect of intrabrachial insulin
      on the changes in forearm blood flow (strain-gauge plethysmography) induced by
      intrabrachial acetylcholine (at doses of 0.15, 0.45, 1.5, 4.5, and 15
      micrograms.min-1.dL-1), an endothelium-dependent vasodilator, or sodium
      nitroprusside (at doses of 1, 2, and 4 micrograms.min-1.dL-1), and endothelium
      independent vasodilator. Local hyperinsulinemia (deep venous plasma insulin, 48
      +/- 6 and 51 +/- 5 microU/mL in control subjects and hypertensive patients,
      respectively) did not affect basal forearm blood flow and stimulated forearm
      glucose extraction (control subjects, 3 +/- 1% to 11 +/- 2%, P < .001;
      hypertensive patients, 3 +/- 1% to 6 +/- 1%, P < .001; P < .01 for the between
      group difference). In both normotensive and hypertensive subjects, insulin
      significantly potentiated acetylcholine-induced vasodilation, whereas it did not
      alter the vasodilatory response to sodium nitroprusside. NG-monomethyl-L
      arginine, an inhibitor of endothelial nitric oxide synthesis, blunted insulin
      induced facilitation of acetylcholine vasodilation in normotensive but not in
      hypertensive subjects. In contrast, in hypertensive patients but not in
      normotensive control subjects, the potentiation of the vascular response to
      acetylcholine induced by local hyperinsulinemia was abolished by intrabrachial
      ouabain, an inhibitor of Na(+)-K+ pump. CONCLUSIONS: In healthy humans and
      essential hypertensive patients alike, local physiological hyperinsulinemia per
      se does not increase forearm blood flow but potentiates the vasodilation induced
      by acetylcholine regardless of metabolic insulin resistance. This effect is
      endothelium-dependent because it is not seen with nitroprusside and is related to
      the L-arginine-nitric oxide pathway in normotensive subjects and to smooth muscle
      cell hyperpolarization in essential hypertensive patients.

PMID- 7586258
TI  - Positive and negative inotropic effects of DL-sotalol and D-sotalol in failing
      and nonfailing human myocardium under physiological experimental conditions.
AB  - BACKGROUND: DL-Sotalol has class III antiarrhythmic activity through prolongation
      of the repolarization phase of the action potential as well as beta-adrenoceptor
      blocking properties. Although the former effect was found to exert positive
      inotropic effects in animal experimental studies, the latter may be detrimental
      in heart failure due to negative inotropism. In contrast to DL-sotalol, D-sotalol
      is suggested to exert only positive inotropic effects, which were never tested in
      isolated human myocardium. METHODS AND RESULTS: Therefore, we investigated the
      effects of racemic DL-sotalol and its enantiomer D-sotalol in human right atrial
      muscle strip preparations and in left ventricular muscle strip preparations from
      nonfailing and end-stage failing human hearts. DL-sotalol and D-sotalol
      significantly (P < .01) increased peak developed force in atrial preparations by
      14.0 +/- 3.4% and 16.7 +/- 3.8%, respectively, but had no effect in ventricular
      myocardium. In nonfailing ventricular myocardium, both DL-sotalol and D-sotalol
      shifted the dose-response curve for isoproterenol to higher concentrations (P <
      .01); however, DL-sotalol was 100-fold more effective than D-sotalol. In non
      failing myocardium, a positive force-frequency relation was found between 30 and
      120 beats per minute, but isoproterenol was much more powerful in its inotropic
      effects. In failing myocardium, reduction in stimulation rate from 120 to 30
      beats per minute increased peak developed force more pronounced than did the
      application of isoproterenol. CONCLUSIONS: (1) D-Sotalol has no relevant beta
      adrenoceptor-blocking activity compared with DL-sotalol. (2) Neither DL-sotalol
      nor D-sotalol exhibit positive inotropic effects in human left ventricular
      myocardium. (3) Heart rate reduction increases contractile force in end-stage
      failing human myocardium due to an inverse force-frequency relation and thereby
      counteracts the potential negative inotropic properties of beta-blockade.

PMID- 7586260
TI  - Radiofrequency catheter modification of the sinus node for "inappropriate" sinus
      tachycardia.
AB  - BACKGROUND: Radiofrequency catheter ablation is the treatment of choice for
      patients with paroxysmal supraventricular tachycardias refractory to medical
      therapy. However, in symptomatic patients with inappropriate sinus tachycardia
      resistant to drug therapy, catheter ablation of the His' bundle with permanent
      pacemaker insertion is currently applied. We evaluated the safety and efficacy of
      radiofrequency modification of the sinus node as alternative therapy for patients
      with inappropriate sinus tachycardia. METHODS AND RESULTS: Sixteen patients with
      disabling episodes of inappropriate sinus tachycardia refractory to drug therapy
      (4.2 +/- 0.3 drug trials) underwent either total sinus node ablation or sinus
      node modification. The region of the sinus node was identified as the region of
      earliest atrial activation in sinus rhythm during electrophysiological study.
      This region was further defined by use of intracardiac echocardiography (ICE) in
      9 patients, in whom it was found that an ablation catheter could be guided
      reliably and maintained on the crista terminalis. Radiofrequency energy was
      delivered during tachycardia between either a standard 4-mm or custom 10-mm
      thermistor-imbedded catheter tip and a skin patch. Total sinus node ablation was
      performed successfully in all 4 patients in whom it was attempted and was
      characterized by a junctional escape rhythm. Sinus node modification was
      successfully achieved in all 12 patients in whom it was attempted and was
      characterized by a 25% reduction in the sinus heart rate. For the group as a
      whole, exercise stress testing after ablation revealed a gradual chronotropic
      response, with a significant reduction in maximal heart rate (132.8 +/- 6.5
      versus 179.5 +/- 3.6 beats per minute [bpm]; P < .001) without evidence of an
      exaggerated heart rate response to a light workload (103.0 +/- 4.1 versus 139.5
      +/- 3.5 bpm; P < .001). Twenty-four-hour ambulatory ECG monitoring revealed a
      significant decrease in maximal heart rate and mean heart rate after ablation
      (167.2 +/- 2.6 versus 96.7 +/- 5.0 bpm, P < .001, and 125.6 +/- 5.0 versus 54.1
      +/- 5.3 bpm, P < .001, respectively). There was a significant decrease in the
      number of applications of radiofrequency energy required in patients undergoing
      modification of the sinus node when guided by ICE compared with fluoroscopy alone
      (3.6 +/- 0.8 versus 10.4 +/- 2.1; P < .01) as well as a decrease in fluoroscopy
      time (33.0 +/- 9.5 versus 58.5 +/- 8.4 minutes). After a mean follow-up period of
      20.5 +/- 0.3 months, there were no recurrences of inappropriate sinus tachycardia
      in patients who underwent a total sinus node ablation. However, 2 patients who
      had a total sinus node ablation subsequently required permanent pacing because of
      symptomatic pauses, and 1 patient developed an ectopic atrial tachycardia. After
      a mean follow-up of 7.1 +/- 1.7 months, there were two recurrences of
      inappropriate sinus tachycardia in patients who underwent sinus node
      modification. However, no significant bradycardia or pauses were observed.
      Complications encountered during the study included 1 patient who developed
      transient right diaphragmatic paralysis and another patient who developed
      transient superior vena cava syndrome. CONCLUSIONS: Sinus node modification is
      feasible in humans and should be considered as an alternative to complete
      atrioventricular junctional ablation for patients with disabling inappropriate
      sinus tachycardia refractory to medical management. Sinus node modification may
      be aided by ICE.

PMID- 7586261
TI  - ECG T-wave patterns in genetically distinct forms of the hereditary long QT
      syndrome.
AB  - BACKGROUND: The long QT syndrome is an inherited disorder with prolonged
      ventricular repolarization and a propensity to ventricular tachyarrhythmias and
      sudden arrhythmic death. Recent linkage studies have demonstrated three separate
      loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes
      for long QT syndrome have been identified on two of these chromosomes. We
      investigated ECG T-wave patterns (phenotypes) in members of families linked to
      three genetically distinct forms of the long QT syndrome. METHODS AND RESULTS:
      Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time
      intervals (QTonset-c, QTpeak-c, QTc, and Tduration-c, in milliseconds) and the
      absolute height of the T wave (Tamplitude, in millivolts), were measured in 153
      members of six families with long QT syndrome linked to markers on chromosomes 3
      (n = 47), 7 (n = 30), and 11 (n = 76). Genotypic data were used to define each
      family member as being affected or unaffected with long QT syndrome. Affected
      members of all six families had longer QT intervals (QTonset-c, QTpeak-c, or QTc)
      than unaffected family members (P < .01). Each of the three long QT syndrome
      genotypes was associated with somewhat distinctive ECG repolarization features.
      Among affected individuals, the QTonset-c was unusually prolonged in those
      individuals with mutations involving the cardiac sodium channel gene SCN5A on
      chromosome 3 (lead II QTonset-c [mean +/- SD]: chromosome 3, 341 +/- 42 ms;
      chromosome 7, 290 +/- 56 ms; chromosome 11, 243 +/- 73 ms; P < .001); Tamplitude
      was generally quite small in the chromosome 7 genotype (lead II Tamplitude, mV:
      chromosome 3, 0.36 +/- 0.14; chromosome 7, 0.13 +/- 0.07; chromosome 11, 0.37 +/-
      0.17; P < .001); and Tduration was particularly long in the chromosome 11
      genotype (lead II Tduration-c: chromosome 3, 187 +/- 33 ms; chromosome 7, 191 +/-
      51 ms; chromosome 11, 262 +/- 65 ms; P < .001). Similar ECG findings were
      observed in leads aVF and V5. A considerable variability exists in the
      quantitative repolarization parameters associated with each genotype, with
      overlap in the T-wave patterns among the three genotypes. CONCLUSIONS: Three
      separate genetic loci for the long QT syndrome including mutations in two cardiac
      ionic channel genes were associated with different phenotypic T-wave patterns on
      the ECG. This study provides insight into the influence of genetic factors on ECG
      manifestations of ventricular repolarization.

PMID- 7586263
TI  - A prospective randomized evaluation of implantable cardioverter-defibrillator
      size on unipolar defibrillation system efficacy.
AB  - BACKGROUND: The active can unipolar implantable cardioverter-defibrillator (ICD)
      has been shown to defibrillate efficiently, but its current 80-cc size limits use
      in the pectoral position in many patients. Decreasing can size will facilitate
      pectoral insertion and will soon be feasible as an inevitable consequence of
      technological advancements. However, decreasing the can size has the potential to
      compromise unipolar defibrillation efficacy. It is the purpose of this study,
      therefore, to prospectively and randomly compare unipolar defibrillation efficacy
      with 80-cc, 60-cc, and 40-cc can sizes in patients immediately before ICD surgery
      in anticipation of advances in technology that will make smaller ICDs possible.
      METHODS AND RESULTS: Twenty-four consecutive patients underwent prospective,
      randomized evaluation of the effect of ICD can size on defibrillation efficacy
      during standard ICD surgery. Each patient had the unipolar defibrillation
      threshold (DFT) measured with 80-cc, 60-cc, or 40-cc active can placed in the
      left subcutaneous infraclavicular region. The system included a 10.5F tripolar
      right ventricular electrode that served as the shock anode. The shock waveform
      used in each instance was a single capacitor biphasic 65% pulse delivered from a
      120-microF capacitor. Stored energy at the DFT for the 80-cc, 60-cc, and 40-cc
      cans were 8.1 +/- 4.7 J, 8.7 +/- 5.8 J, and 9.5 +/- 4.8 J, respectively. There
      was no statistical significant difference between the DFTs for the three unipolar
      can electrodes (P = 39). Leading edge voltage also did not differ significantly
      among the three unipolar cans (356 +/- 92 V, 365 +/- 110 V, and 387 +/- 94 V,
      respectively, P = .29). There was, however, a slight progressive increase in
      resistance with decreasing can size (57 +/- 7 omega, 60 +/- 9 omega, and 65 +/- 9
      omega, respectively, P < .001). CONCLUSIONS: Decreasing can volume from 80 cc to
      60 cc to 40 cc does not compromise unipolar defibrillation efficacy despite a
      slight rise in shock resistance. These findings indicate that technological
      advances that allow for smaller-volume ICDs will not compromise defibrillation
      efficacy for unipolar systems.

PMID- 7586262
TI  - Steroid elution improves the stimulation threshold in an active-fixation atrial
      permanent pacing lead. A randomized, controlled study. Model 4068 Investigators.
AB  - BACKGROUND: Prior work suggests that the addition of a steroid-eluting reservoir
      to a passive-fixation permanent pacemaker lead improves the stimulation
      threshold; however, no large randomized study has addressed this tissue. Over the
      last several years, there has been an increase in enthusiasm for the use of
      active-fixation permanent pacemaker leads for various reasons in spite of the
      generally accepted notion that active-fixation leads have higher stimulation
      thresholds. METHODS AND RESULTS: This multicenter, randomized, controlled study
      examined the difference in performance between a standard active-fixation atrial
      lead (Medtronic model 4058) and a steroid-eluting lead (Medtronic model 4068).
      Stimulation thresholds were obtained in a four-point strength-duration fashion.
      Evaluations of sensing and impedance were performed as well. These evaluations
      were performed at implantation, at weeks 1 through 4, and at weeks 6, 12, 24, and
      52. Stimulation thresholds were significantly better in the steroid lead than in
      the nonsteroid lead at each measurement point from 1 week to 12 months. The mean
      1.6-V stimulation threshold at 12 months was 0.19 +/- 0.2 ms in the steroid lead
      and 0.41 +/- 0.30 ms in the control lead. No acute peaking was observed with the
      steroid lead, whereas significant peaking was observed with the control lead.
      There was no difference in long-term sensing or impedance. CONCLUSIONS: Inclusion
      of a steroid-eluting reservoir in an active-fixation permanent pacing lead
      improved stimulation thresholds in both the subacute and chronic periods and
      therefore should extend pulse-generator longevity.

PMID- 7586267
TI  - Plasma endothelin correlates with antiendothelial antibodies in patients with
      mixed connective tissue disease.
AB  - BACKGROUND: Elevated circulating levels of the vasoactive peptide endothelin-1
      have been reported in various cardiovascular disorders. Because these conditions
      are frequently associated with endothelial dysfunction and damage and the
      vasoconstrictor effect of endothelin-1 is believed to be produced at the local
      vascular level, it is uncertain whether circulating endothelin-1 is a causal
      factor in enhanced vascular tone or instead a marker of endothelial injury.
      METHODS AND RESULTS: We tested whether elevated immunoreactive endothelin-1 could
      be detected by radioimmunoassay in plasma and whether endothelin-1 levels
      correlated with antiendothelial autoantibodies in patients with mixed connective
      tissue disease. Venous blood samples were collected from 21 patients in the
      morning after an overnight fast and before medication. The plasma immunoreactive
      endothelin-1 level was 2.7 +/- 0.5 pg/mL (range, 1.1 to 5.2 pg/ml; n = 9) and 7.3
      +/- 1.5 pg/mL (range, 2.8 to 20.7 pg/mL; n = 12) in patients who had no
      antiendothelial antibodies and in patients with antiendothelial antibodies,
      respectively. These latter values were significantly (P < .001) increased
      compared with 10 age-matched healthy volunteers (2.0 +/- 0.3 pg/mL; range, 0.5 to
      3.0 pg/mL). Plasma endothelin-1 level strongly correlated with antiendothelial
      antibodies (rs = .836, n = 21, P < .001), whereas there was no correlation
      between age, systolic and diastolic blood pressures, antinuclear antibodies, and
      duration of the disease and endothelin-1 values. The incidence of Raynaud's
      phenomenon and angina did not differ significantly in patients with low and high
      endothelin-1 levels. CONCLUSIONS: This study showed that mixed connective tissue
      disease is associated with elevated plasma immunoreactive endothelin-1 and that
      endothelin-1 levels significantly correlate with antiendothelial autoantibodies.
      These findings suggest that increases in plasma endothelin-1 concentration may be
      secondary to vascular injury and do not necessarily represent enhanced
      susceptibility to vasoconstriction.

PMID- 7586264
TI  - Antiarrhythmic activity of quinine in humans.
AB  - BACKGROUND: Quinine is the diastereomer of quinidine. In dogs, it has similar
      effects on conduction time but does not prolong epicardial repolarization time or
      ventricular refractoriness. It has antiarrhythmic effects in both cats and dogs.
      We assessed the antiarrhythmic potential of quinine in suppressing ventricular
      arrhythmias in humans. METHODS AND RESULTS: Patients underwent open-label, dose
      ranging trials of quinine with daily doses of 600, 1200, and 1800 mg in a twice
      daily dosing regimen. In 17 patients with frequent spontaneous ventricular
      ectopy, oral quinine suppressed arrhythmia in 11 of 12 patients who finished the
      study and was not tolerated by 4 patients, and 1 patient withdrew from the study.
      The mean effective daily dosage was 927 mg, the mean effective trough serum level
      was 11 mumol/L (range, 4 to 17 mumol/L), and the half-life was 20 +/- 7 hours. In
      a second open-label, dose-ranging trial in 10 patients with inducible ventricular
      tachycardia and reduced left ventricular systolic function (left ventricular
      ejection fraction, 35 +/- 16%), quinine suppressed inducibility of ventricular
      tachycardia in 3 of 10 patients. At a basic pacing cycle length of 500
      milliseconds, ventricular effective refractory period was prolonged (279 +/- 21
      versus 247 +/- 10 milliseconds, quinine versus drug free, P = .003). In the
      remaining patients, ventricular tachycardia cycle length was prolonged (373 +/-
      48 versus 253 +/- 30 milliseconds, quinine versus drug free, P < .001). The
      corrected QT interval was not prolonged. CONCLUSIONS: Quinine is an effective and
      convenient antiarrhythmic drug for the suppression of ventricular arrhythmias in
      humans.

PMID- 7586268
TI  - Progesterone receptor expression in human saphenous veins.
AB  - BACKGROUND: Clinical and epidemiological observations regarding varicose veins,
      such as their predominance in women and the occurrence of venous stasis during
      sex-hormone therapy, the luteal phase of the menstrual cycle, and pregnancy,
      suggest a sex hormone-dependency of this venous pathology. In the present study,
      analysis of steroid receptors was used to determine if these effects were due to
      a direct hormonal action on the saphenous vein. METHODS AND RESULTS: Biopsy
      samples were obtained from patients undergoing stripping removal of varicose
      saphenous veins. Patients were men (n = 5) and premenopausal (n = 15) or
      postmenopausal (n = 10) women. Progesterone receptors (PR) and estrogen receptors
      (ER) were determined by both enzyme immunoassay (EIA) and immunocytochemistry by
      use of monoclonal antibodies. Ninety percent of the biopsy samples showed PR
      positivity by EIA (range, 5 to 53 fmol/mg cytosol protein). When present, PR
      staining was observed in the cell nuclei of the tunica media and the
      subendothelial layer (neointima). No significant variation was observed in the PR
      content of different regions within the same saphenous vein. In contrast, no ER
      or extremely low levels of ER (< 5 fmol/mg cytosol protein) were detected by EIA
      in 25 of 30 varicose biopsy samples. Reverse transcription-polymerase chain
      reaction (RT-PCR) was used to analyze PR and ER mRNAs in biopsy samples that were
      PR positive/ER negative. With primers to the hormone-binding region encoded by PR
      mRNA, a RT-PCR product of the expected size was detected and its identity
      confirmed by Southern blot by use of a PR cDNA probe. In contrast, no RT-PCR
      product could be detected by use of primers to the DNA-binding domain, the hinge
      region, and the ligand-binding domain encoded by ER mRNA. CONCLUSIONS: These
      results indicate that human saphenous veins from both sexes express PR, as
      previously described for arterial blood vessels. This observation suggests that
      progesterone acts directly on these veins via a classic receptor-mediated
      pathway.

PMID- 7586265
TI  - Changes in effective regurgitant orifice throughout systole in patients with
      mitral valve prolapse. A clinical study using the proximal isovelocity surface
      area method.
AB  - BACKGROUND: In patients with mitral valve prolapse, spontaneous changes of the
      effective regurgitant orifice during systole are not well documented. Such
      changes can now be analyzed by use of the proximal isovelocity surface area
      method, but the changes raise concern about the reliability of this method for
      assessing overall severity of regurgitation in these patients. METHODS AND
      RESULTS: In a prospective study of 42 patients with mitral valve prolapse, the
      effective mitral regurgitant orifice was calculated at four phases of systole
      (early, mid, mid-late, and late) as the ratio of regurgitant flow to regurgitant
      velocity by use of the proximal isovelocity surface area method. Throughout
      systole, the effective regurgitant orifice increased significantly, from 32 +/-
      27 mm2 in early systole to 41 +/- 27 in midsystole, 55 +/- 30 in mid-late
      systole, and 107 +/- 66 mm2 during late systole (P < .0001). Phasic regurgitant
      volume increased from early to mid-late systole but decreased in late systole.
      For quantitation of the overall effective regurgitant orifice, four approaches
      using the proximal isovelocity surface area were compared with simultaneously
      performed quantitative Doppler echocardiography (54 +/- 30 mm2) and quantitative
      two-dimensional echocardiography (51 +/- 29 mm2). All correlations were good (r >
      .95), but overestimation was considerable when the largest flow convergence was
      used (70 +/- 39 mm2; both P < .0001), significant when the simple mean of the
      four phases was used (59 +/- 36 mm2; P = .005 and P = .0007, respectively), mild
      when a weighted mean of the four phases was used (55 +/- 33 mm2; P = .41 and P =
      .01, respectively), and no overestimation was observed when the effective
      regurgitant orifice calculated at maximum regurgitant velocity was used (54 +/-
      30 mm2; P = .29 and P = .17, respectively). CONCLUSIONS: Phasic changes of mitral
      regurgitation are observed in patients with mitral valve prolapse. The effective
      regurgitant orifice increases throughout systole. Regurgitant volume also
      increases initially but tends to decrease in late systole. These changes can lead
      to overestimation of the overall degree of regurgitation, but properly timed
      measurements made by use of the proximal isovelocity surface area method allow an
      accurate estimation of the overall effective regurgitant orifice.

PMID- 7586270
TI  - Vascular injury, repair, and restenosis after percutaneous transluminal
      angioplasty in the atherosclerotic rabbit.
AB  - BACKGROUND: Several nonatherosclerotic animal models of restenosis exist and are
      used for the evaluation of the vascular response to angioplasty-induced injury.
      However, few studies have evaluated the response of an atherosclerotic vessel to
      angioplasty. The present study examined the radiographic, histological,
      immunohistochemical, and morphometric responses over time of atherosclerotic
      rabbit femoral arteries after percutaneous transluminal angioplasty (PTA).
      METHODS AND RESULTS: Rabbits (n = 94) underwent arterial dissection and were fed
      a hypercholesterolemic diet for 3 weeks, and then PTA was performed. Arteries
      were obtained before PTA and 1, 3, 5, 7, 14, and 28 days after PTA. PTA caused
      radial stretching of the artery, medial compression, intramural hemorrhage,
      injury to normal arterial segments, and dissection within the intima and media.
      Thrombus filled and cellular accumulation repaired the dissection. Peak smooth
      muscle cell and macrophage DNA synthesis was noted at 3 to 5 days after
      angioplasty, generally at the dissection but also in normal sections of the
      artery. Adventitial injury and subsequent adventitial cellular proliferation and
      collagen production were observed. A rapid decrease in the radiographic minimal
      luminal diameter was noted at 3 days, resulting from vascular recoil or thrombus
      filling the dissection. At 7 to 14 days, only 24% to 33% of the luminal loss was
      accounted for by an increase in the intimal area, and 22% to 28% of the intima
      was neointima. CONCLUSIONS: Restenosis in an atherosclerotic artery results from
      a variable combination of intimal proliferation, vascular remodeling/wound
      contraction, and recoil of the normal section of the artery. The variability of
      an atherosclerotic artery to PTA injury results from variable dissection,
      thrombus formation, and cellular response to injury as well as variable scar
      contraction and elastic recoil.

PMID- 7586269
TI  - The circulatory regulation of TPA and UPA secretion, clearance, and inhibition
      during exercise and during the infusion of isoproterenol and phenylephrine.
AB  - BACKGROUND: Exercise to exhaustion and infusions of isoproterenol and
      phenylephrine were used to study interactions between plasminogen activator
      regulation and the control of regional blood flow in 10 healthy males. METHODS
      AND RESULTS: Experimental measurements of cardiac output, heart rate, tissue
      plasminogen activator (TPA), urokinase plasminogen activator (UPA), plasminogen
      activator inhibitor (PAI-1), C1-inhibitor, and TPA/C1-inhibitor complex during
      the infusions and exercise were used to develop a comprehensive fluid-phase model
      of the circulatory regulation of fibrinolysis. alpha- and beta-adrenergic
      agonists increased TPA and UPA in plasma by different mechanisms: Phenylephrine
      decreased hepatic blood flow and thus clearance while isoproterenol stimulated
      increased secretion of TPA and UPA. Exercise to exhaustion increased TPA and UPA
      through a combination of increased secretion and decreased clearance. The time
      course of UPA and TPA release were similar, but the magnitude of their secretion
      responses differed. In vivo, C1-inhibitor bound to TPA at a rate of 553 mol-1.s
      1. C1-inhibitor contributed equally with PAI-1 to TPA inhibition when active PAI
      1 levels were low (20 to 50 pmol/L) but was less important when active PAI-1
      levels were high. CONCLUSIONS: We conclude that secretion, inhibition, clearance,
      and regional blood flow effects must all be taken into account when evaluating
      changes in plasminogen activator levels.

PMID- 7586266
TI  - Role of transesophageal echocardiography in the diagnosis and management of
      traumatic aortic disruption.
AB  - BACKGROUND: Traumatic disruption of the aorta (TDA) is a life-threatening injury
      that requires rapid diagnosis and treatment. Emergency aortography, which is the
      current standard diagnostic imaging modality, is invasive, time-consuming, and
      difficult to perform in hemodynamically unstable patients with multiple trauma.
      We performed transesophageal echocardiography (TEE) in patients with suspected
      TDA to determine the diagnostic accuracy and impact on patient management of this
      alternative, portable imaging modality. METHODS AND RESULTS: Thirty-two
      consecutive trauma patients (mean age, 40 +/- 16 years) with suspected TDA
      (violent deceleration accident and mediastinum > 8 cm on admission chest x-ray)
      prospectively underwent a TEE examination in the emergency room. Findings during
      TEE were compared with those encountered during aortography, surgery, or
      necropsy. Two subsets of traumatic aortic injuries with distinct
      echocardiographic signs were observed: (1) subadventitial TDA (n = 10) and (2)
      traumatic intimal tears (n = 3). Eighteen patients had normal TEE confirmed by
      aortography. One 2-mm medial tear was missed by TEE (necropsy). The sensitivity
      and specificity of TEE for the diagnosis of subadventitial TDA were 91% and 100%,
      respectively. Patients with subadventitial TDA were taken to surgery immediately,
      whereas patients with intimal aortic tears were treated conservatively. Eighteen
      patients (mean age, 57 +/- 15 years) with confirmed acute aortic dissection
      involving the aortic isthmus were also included to establish the
      echocardiographic differential diagnostic criteria between this entity and TDA.
      CONCLUSIONS: TEE should be considered the first-line imaging modality for the
      evaluation of trauma patients with suspected injuries of the thoracic aorta
      because of its portability, safety, diagnostic accuracy, and potential impact on
      patient management.

PMID- 7586271
TI  - Dose-dependent dissociation of ACE-inhibitor effects on blood pressure, cardiac
      hypertrophy, and beta-adrenergic signal transduction.
AB  - BACKGROUND: Dose-dependent effects of ACE inhibitors on blood pressure, cardiac
      hypertrophy, and beta-adrenergic signal transduction were examined in an animal
      model with beta-adrenergic desensitization, which has been identified in failing
      hearts and in hypertensive cardiac hypertrophy. It is unknown whether beneficial
      ACE-inhibitor effects are due to an unloading of the failing heart or a reduction
      of neuroendocrine activation with beta-adrenergic resensitization. METHODS AND
      RESULTS: Low-dose (LD, 1 mg/kg) and high-dose (HD, 25 mg/kg) fosinopril treatment
      was performed in spontaneously hypertensive rats (SHR) and control (WKY) rats.
      Myocardial norepinephrine concentrations, adenylyl cyclase activity, beta
      adrenergic receptors (radioligand binding), Gs alpha (functional reconstitution),
      and Gi alpha (pertussis toxin labeling) were determined. Ventricular weights and
      blood pressures were measured. HD but not LD reduced blood pressure and left
      ventricular weights in SHR. Isoprenaline- and guanylylim-idodiphosphate
      stimulated adenylyl cyclase activities as well as beta 1-adrenergic receptors
      were reduced in SHR. The catalyst and Gs alpha were unchanged, but Gi alpha and
      norepinephrine concentrations were increased. Both LD and HD treatments restored
      beta-adrenergic alteration. CONCLUSIONS: LD treatment with ACE inhibitors
      restored beta-adrenergic signal transduction defects independently of regression
      of cardiac hypertrophy. This could contribute to the effects of ACE inhibitors in
      patients, who are often treated with nonhypotensive doses.

PMID- 7586272
TI  - Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig
      ventricular myocytes.
AB  - BACKGROUND: Bupivacaine is a potent local anesthetic widely used for prolonged
      local and regional anesthesia. However, accidental intravascular injection of
      bupivacaine can produce severe arrhythmias and cardiac depression. Although used
      clinically as a racemic mixture, S(-)-bupivacaine appears less toxic than the
      R(+)-enantiomer despite at least equal potency for local anesthesia. If the R(+)
      enantiomer is more potent in blocking cardiac sodium channels, then the S(-)
      enantiomer could be used with less chance of cardiovascular toxicity. Therefore,
      we tested whether such stereoselectivity existed in the bupivacaine affinity for
      the cardiac sodium channel. METHODS AND RESULTS: The inhibitory effects on the
      cardiac sodium current (INa) of 10 mumol/L R(+)- and S(-)-bupivacaine were
      investigated by use of the whole-cell voltage clamp technique in isolated guinea
      pig ventricular myocytes. Both enantiomers produced similar but limited levels of
      tonic block (6% and 8%). During long depolarizations (5 seconds at 0 mV), R(+)
      bupivacaine induced a significantly larger inhibition of INa: 72 +/- 2% versus 58
      +/- 3% for the S(-)-enantiomer (P < .01). Development of block was slow, but its
      rate was faster for R(+)-bupivacaine [time constant, 1.84 +/- 0.16 versus 2.56 +/
      0.26 seconds for the S(-)-enantiomer, P < .05]. The voltage dependence of the
      availability of the Na+ current was shifted to more hyperpolarizing potentials
      compared with the control; R(+)-bupivacaine induced a larger shift than S(-)
      bupivacaine (37 +/- 2 versus 30 +/- 2 mV, P < .05). These data indicate
      stereoselective interactions with the inactivated state. In addition, both
      enantiomers induced substantial use-dependent block during 2.5-Hz pulse trains
      with medium (100-ms) and short (10-ms) depolarizations but without
      stereoselective difference. A stepwise approach was used to model these
      experimental results and to derive apparent affinities and rate constants. We
      initially assumed that bupivacaine interacted only with the rested and
      inactivated states of the Na+ channel. The apparent affinities of the inactivated
      state for S(-)- and R(+)-bupivacaine were 4.8 and 2.9 mumol/L, respectively. With
      the derived binding and unbinding rate constants, this model reproduced the
      stereoselective block during long depolarizations but failed to predict the use
      dependent block induced by trains of short (10-ms) depolarizations. To account
      for the observed use-dependent interactions, it was necessary to include
      interactions with the activated state, which resulted in adequate reproduction of
      the experimental results. The apparent affinities of the activated or open state
      for S(-)- and R(+)-bupivacaine were 4.3 and 3.3 mumol/L, respectively.
      CONCLUSIONS: Both the large level of pulse-dependent block and the failure of the
      pure inactivated-state block model indicate that bupivacaine interacts with the
      activated (or open) state of the cardiac sodium channel in addition to its block
      of the inactivated state. The bupivacaine-induced block of the inactivated state
      of the Na+ channel displayed stereoselectivity, with R(+)-bupivacaine interacting
      faster and more potently. Both enantiomers also bind with high affinity to the
      activated or open state of the channel, but this interaction did not display
      stereoselectivity, although the binding to the activated or open state was faster
      for S(-)- than for R(+)-bupivacaine. The higher potency of R(+)-bupivacaine to
      block the inactivated state of the cardiac Na+ channel may explain its higher
      toxicity because of the large contribution of the inactivated-state block during
      the plateau phase of the cardiac action potential. These results would support
      the use of the S(-)-enantiomer to reduce cardiac toxicity.

PMID- 7586273
TI  - Intracoronary low-dose beta-irradiation inhibits neointima formation after
      coronary artery balloon injury in the swine restenosis model.
AB  - BACKGROUND: Neointima formation contributing to recurrent stenosis remains a
      major limitation of percutaneous transluminal angioplasty. Endovascular low-dose
      gamma-irradiation has been shown to reduce intimal thickening (hyperplasia) after
      balloon overstretch injury in pig coronary arteries, a model of restenosis. The
      objective of this study was to determine whether the use of a beta-emitting
      radioisotope for this application would have similar effects and to examine the
      dose-response relations with this approach. METHODS AND RESULTS: Normal domestic
      pigs underwent balloon overstretch injury in the left anterior descending and
      left circumflex and coronary arteries. A flexible catheter was introduced by
      random assignment into one of these arteries and was afterloaded with a 2.5-cm
      ribbon of encapsulated 90Strontium/90Yttrium sources (90Sr/Y, a pure beta
      emitter). It was left in place for a period of time sufficient to deliver one of
      four doses: 7, 14, 28, or 56 Gy, to a depth of 2 mm. Animals were killed 14 days
      after balloon injury, the coronary vasculature was pressure-perfusion fixed, and
      histomorphometric analysis of arterial cross sections was performed. All arteries
      treated with radiation demonstrated significantly decreased neointima formation
      compared with control arteries. The ratio of intimal area to medial fracture
      length was inversely correlated with increasing radiation dose: control (no
      radiation), 0.47; 7 Gy, 0.34; 14 Gy, 0.20; 28 Gy, 0.08; and 56 Gy, 0.02 (r = 
      .78, P < .000001). Scanning electron microscopy demonstrated a confluent layer of
      endothelium-like cells both in control and in 14 Gy-irradiated arteries. There
      was neither evidence of significant necrosis nor excess fibrosis in the media,
      adventitia, or perivascular space of the coronary arteries or adjacent myocardium
      in the irradiated groups. Furthermore, the exposure to the staff and the total
      body exposure to the pig with the beta source was a small fraction of the dose
      previously measured and calculated with 192Ir, a gamma-emitting radioisotope.
      CONCLUSIONS: Administration of endovascular beta-radiation to the site of
      coronary arterial overstretch balloon injury in pigs with 90Sr/Y is technically
      feasible and safe. Radiation doses between 7 and 56 Gy showed evidence of
      inhibition of neointima formation. A dose-response relation was demonstrated, but
      no further inhibitory effect was seen beyond 28 Gy. These data suggest that
      intracoronary beta-irradiation is practical and feasible and may aid in
      preventing clinical restenosis.

PMID- 7586274
TI  - New variant of human tissue plasminogen activator (TPA) with enhanced efficacy
      and lower incidence of bleeding compared with recombinant human TPA.
AB  - BACKGROUND: The thrombolytic properties of a new variant of tissue plasminogen
      activator (TPA) (T103N, N117Q, KHRR 296-299 AAAA, or TNK-TPA) with longer plasma
      half-life, greater fibrin specificity, and increased resistance to inhibition by
      plasminogen activator inhibitor (PAI-1) were investigated in a rabbit thrombosed
      carotid artery model. METHODS AND RESULTS: After 60 minutes of arterial
      occlusion, TPA (1.5, 3.0, 6.0, or 9.0 mg/kg as a front-loaded IV infusion for 90
      minutes; n = 22) or TNK-TPA (0.38, 0.75, or 1.5 mg/kg as IV bolus; n = 16) was
      administered. Blood flow through the artery was monitored for an additional 120
      minutes. Bleeding was assessed by weighing the amount of blood absorbed in a
      gauze pad placed in a subcutaneous muscular incision. Recanalization rates and
      duration of recanalization were dose dependent. The doses that produced > 80%
      recanalization rates with the longest duration of recanalization were 9.0 mg/kg
      for TPA and 1.5 mg/kg for TNK-TPA. At these doses, time to reperfusion (mean +/-
      SEM) was significantly faster (11 +/- 2 versus 23 +/- 7 minutes) and duration of
      recanalization longer (77 +/- 9 versus 51 +/- 18 minutes) for TNK-TPA compared
      with TPA (P < .025). Weights of the residual thrombi of the TPA group were
      greater than those of the TNK-TPA group (P = .004). Concentrations of fibrinogen,
      plasminogen, and alpha 2-antiplasmin at 120 minutes were significantly higher for
      TNK-TPA-treated animals compared with TPA-treated animals (P < .001). ANOVA of
      the blood loss data determined that there were significant differences between
      thrombolytic agents but not between doses. After correction for saline controls,
      total blood loss for pooled doses of TPA and TNK-TPA was 82 +/- 6 mg and 40 +/- 4
      mg, respectively (P < .01). CONCLUSIONS: From these data, we conclude that TNK
      TPA, given as a bolus, produces faster and more complete recanalization of
      occluded arteries in a rabbit experimental model compared with TPA, without
      increasing systemic plasmin generation or peripheral bleeding. In addition, we
      observed that TNK-TPA, unlike TPA, did not potentiate collagen-induced
      aggregation of platelets obtained from human plasma. This lack of effect on
      platelet aggregation by TNK-TPA potentially could be associated with a decreased
      risk of reocclusion after successful thrombolysis.

PMID- 7586275
TI  - Influence of blockade at specific levels of the coagulation cascade on restenosis
      in a rabbit atherosclerotic femoral artery injury model.
AB  - BACKGROUND: The relation among the coagulation cascade, its individual proteins,
      and the response to vascular injury is largely undefined. We have evaluated the
      effect of four probes that block specific levels of coagulation cascade on
      neointimal hyperplasia in the atherosclerotic rabbit arterial injury model.
      METHODS AND RESULTS: Focal femoral atherosclerosis was induced by air-desiccation
      injury and hypercholesterolemic diet in 48 New Zealand White rabbits, followed by
      balloon angioplasty. Active-site inactivated factor VIIa (DEGR-VIIa), which
      blocks the binding of factor VIIa to tissue factor, was administered (n = 12
      arteries) by intravenous bolus (1 mg/kg) at the time of balloon angioplasty and
      followed by infusion of 50 micrograms.kg-1.h-1 for 3 days; for the control (n =
      13 arteries), 150 U heparin was injected as bolus and followed by infusion of
      saline at 50 microL.kg-1.min-1. Recombinant tissue factor pathway inhibitor
      (TFPI), which binds factor Xa and inhibits the tissue factor-factor VIIa complex
      and factor Xa, was given as a 1 mg/kg bolus followed by 15 micrograms.kg-1.min-1
      infusion for 3 days (n = 17 arteries). Recombinant tick anticoagulant peptide
      (TAP; n = 15 arteries) and hirudin (n = 14 arteries), which block factor Xa and
      thrombin, respectively, were administered as a 1 mg/kg bolus followed by 5
      micrograms.kg-1.min-1 infusion for 3 days. These three groups had their own
      controls (n = 14 arteries). There were no differences among treatment groups in
      preangioplasty and postangioplasty minimal luminal diameter (MLD) by angiography.
      The mean MLD 21 days after balloon angioplasty was significantly different
      between control and DEGR-VIIa-treated groups (0.74 +/- 0.25 and 1.24 +/- 0.27 mm,
      respectively; P = .0001) and between the TFPI-treated group and others (0.88 +/-
      0.21 mm for control, 0.97 +/- 0.22 mm for hirudin-treated, 0.98 +/- 0.14 mm for
      TAP-treated, and 1.32 +/- 0.21 mm for TFPI-treated arteries; P = .0001 by ANOVA).
      By quantitative histological analysis, the ratio of neointimal cross-sectional
      area compared with the area of internal elastic lamina in the DEGR-VIIa-treated
      group was significantly less than control (0.48 +/- 0.12 versus 0.67 +/- 0.12, P
      = .0001), and the ratio of neointimal cross-sectional area to the area demarcated
      by the internal elastic lamina of the TFPI-treated group was significantly
      reduced compared with the other groups (0.46 +/- 0.20 for TFPI-treated, 0.67 +/-
      0.15 for hirudin-treated, 0.61 +/- 0.15 for TAP-treated, and 0.64 +/- 0.13 for
      control groups; P = .003). CONCLUSIONS: Treatment with DEGR-VIIa or TFPI for 3
      days in this rabbit atherosclerotic injury model reduced angiographic restenosis
      and decreased neointimal hyperplasia compared with controls. These findings
      highlight the importance of early initiators of the extrinsic coagulation
      pathway, especially factor VII and tissue factor, in the response to arterial
      injury.

PMID- 7586277
TI  - Regional differences in transient outward current density and inhomogeneities of
      repolarization in rabbit right atrium.
AB  - BACKGROUND: Recent experimental and clinical studies on atrial flutter have
      demonstrated that the crista terminalis (CT) plays an important role in the
      genesis of atrial reentry. To elucidate the underlying mechanism of its role, we
      characterized the electrophysiological repolarization properties of CT cells by
      comparing them with those of the pectinate muscles (PM). METHODS AND RESULTS:
      After action potential properties of both regions were compared by conventional
      microelectrode technique in multicellular atrial tissues, the whole-cell clamp
      experiments were applied in atrial cells isolated from both regions. Action
      potential duration (APD) was more prolonged in CT than in PM in multicellular
      preparations (APD90 77 +/- 5 ms versus 52 +/- 8 ms at 1 Hz, P < .01), though the
      other properties did not differ significantly. Similarly, in isolated atrial
      cells, APD was more prolonged in CT cells than in PM cells (APD90 63 +/- 7 ms
      versus 41 +/- 6 ms at 0.1 Hz, P < .01). Isolated single cells were larger in CT
      than in PM. The whole-cell clamp recordings showed no definite distinctions in
      the density of the voltage-dependent L-type Ca2+ current and the inwardly
      rectifying K+ current between these cells but revealed a significant reduction of
      the density of the 4-aminopyridine-sensitive transient outward current (Ito) in
      CT cells compared with that in PM cells (6.3 +/- 0.7 pA/pF versus 10.3 +/- 0.8
      pA/pF at +20 mV, P < .05). However, no differences in the kinetics or the voltage
      dependence of Ito were observed between the cells. The time course of recovery
      from inactivation of Ito was also similar in both types of cells. CONCLUSIONS:
      These results suggest that the preferential reduction in the density of Ito in
      the CT cells could contribute to prolong their APD, which may be related to the
      genesis of atrial reentry.

PMID- 7586276
TI  - The Ib phase of ventricular arrhythmias in ischemic in situ porcine heart is
      related to changes in cell-to-cell electrical coupling. Experimental Cardiology
      Group, University of North Carolina.
AB  - BACKGROUND: This study was designed to test the hypothesis that the loss of cell
      to-cell electrical interaction during ischemia modulates the amplitude of
      ischemia-induced TQ-segment depression (ie, the injury potential) and the
      occurrence of ventricular fibrillation (VF) during the so-called Ib phase of
      ventricular arrhythmias. METHODS AND RESULTS: Regional ischemia was induced by 60
      minutes of mid-left anterior descending coronary artery ligation in open-chest
      swine (n = 10). Cell-to-cell electrical uncoupling was defined as the onset of
      the terminal rise in whole-tissue resistivity (Rt). Local activation times and TQ
      segment changes (injury potential) were determined from unipolar electrograms.
      Extracellular K+ ([K+]e) and pH (pHe) were measured with plunge-wire ion
      selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow
      ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence
      of VF was positively correlated to the onset of cell-to-cell electrical
      uncoupling (R2 = .885). Cell-to-cell electrical uncoupling superimposed on
      changes of [K+]e and pHe contributed to the failure of impulse propagation
      between 19 and 30 minutes after the arrest of perfusion. During ischemia, maximum
      TQ-segment depression was -10 mV at 19 minutes, after which TQ-segment depression
      slowly recovered. The onset of the TQ-segment recovery was correlated to the
      second rise in Rt (R2 = .886). CONCLUSIONS: In the regionally ischemic in situ
      porcine heart, loss of cell-to-cell electrical interaction is related to the
      occurrence of VF and changes in the amplitude of the injury current. Cellular
      electrical uncoupling contributes to failure of impulse propagation in the
      setting of altered tissue excitability as a result of elevated [K+]e and low pHe.
      These data indicate that Ib arrhythmias and ECG changes during ischemia are
      influenced by the loss of cell-to-cell electrical interaction.

PMID- 7586278
TI  - Radiofrequency catheter modification of sinus pacemaker function guided by
      intracardiac echocardiography.
AB  - BACKGROUND: The sinus P wave arises from a pacemaker complex distributed along
      the crista terminalis. We investigated the feasibility of modification of sinus
      pacemaker function using graded applications of radiofrequency energy along the
      crista terminalis in dogs to achieve sinus rate control. METHODS AND RESULTS:
      Modification of sinus pacemaker function (30 +/- 5% reduction in intrinsic heart
      rate with retention of a normal P-wave axis) was performed in 11 dogs (group 1).
      Total sinus pacemaker ablation (> 50% reduction in intrinsic heart rate with
      development of a low ectopic atrial or a junctional rhythm) was performed in 4
      dogs (group 2). Intracardiac echocardiography was used to identify the crista
      terminalis as an anatomic marker of sinus node location. Sinus pacemaker
      modification caused a significant decrease in intrinsic heart rate (31%
      reduction, P < .001), heart rate responsiveness to isoproterenol (30% reduction,
      P < .0001), and average (20% reduction, P = .0002) and maximal (22% reduction, P
      = .0007) heart rates during 24-hour Holter monitoring. In 6 of the 11 animals,
      the targeted rate reduction of 30 +/- 5% was accurately achieved (mean, 31.6 +/-
      4.3%; P < .001), and in the other 5, significant reduction of intrinsic heart
      rate was achieved but with greater variation (28.0 +/- 17.3%, P < .005).
      Corrected sinus node recovery time was not prolonged. After modification,
      earliest activation was mapped to the crista terminalis inferior to the lesion in
      all animals. In long-term follow-up (3.7 +/- 1.0 months), effects were
      maintained. After total sinus pacemaker ablation, junctional and low atrial
      escape pacemakers were unstable. CONCLUSIONS: This study demonstrates the
      feasibility of modification of sinus pacemaker function for sinus rate control
      using catheter-based radiofrequency ablation guided by intracardiac
      echocardiography. This can be done while pacemaker stability and attenuated
      responsiveness to autonomic influences are preserved. Intracardiac
      echocardiography accurately defined the crista terminalis and provided a reliable
      means to anatomically localize catheter position in relation to the sinus node.

PMID- 7586279
TI  - Influence of epicardial patches on defibrillation threshold with nonthoracotomy
      lead configurations.
AB  - BACKGROUND: In previous studies, epicardial patch electrodes decreased
      transthoracic defibrillation efficacy. We studied the effects of two inactive
      epicardial 14-cm2 titanium mesh patches on defibrillation energy requirements
      with nonthoracotomy internal lead configurations. METHODS AND RESULTS: A 6/6
      millisecond biphasic shock wave-form was delivered via several electrode
      configurations 10 seconds after ventricular fibrillation was initiated with a 60
      Hz generator. In two series, a total of 16 dogs (weight, 23.3 +/- 2.4 kg)
      underwent an up-down defibrillation protocol. In the first series, the
      defibrillation threshold (DFT) was determined for each electrode configuration in
      the presence of two inactive epicardial patches. In the second series, DFTs were
      determined in the presence of an inactive right ventricular (RV) or left
      ventricular (LV) patch alone. For several nonthoracotomy lead configurations
      tested in the first 8 dogs, the mean +/- SD DFT energy increased 49% to 97% with
      two inactive patches on the heart compared with no patches on the heart as
      follows: RV to superior vena caval (SVC) electrode, from 8.9 +/- 2.6 to 18.0 +/-
      14.3 J; RV to SVC plus subcutaneous array electrode, from 7.0 +/- 2.4 to 10.7 +/-
      5.3 J; RV to subcutaneous pectoral plate electrode, from 6.2 +/- 1.3 to 11.4 +/-
      4.0 J (P < or = .05). The lowest DFT was achieved by defibrillating between the
      epicardial patches (3.8 +/- 3.3 J). The second series showed that DFT voltage
      requirements increased significantly for all three nonthoracotomy lead
      configurations with the inactive LV patch alone (P < or = .05) but not with the
      inactive RV patch alone. CONCLUSIONS: Inactive epicardial patches can
      significantly increase the defibrillation energy requirements for nonthoracotomy
      lead configurations. This negative impact may be due to an insulating effect of
      the patches and to a disturbance of the potential gradient field under the
      patches. If the same holds true in patients, these results have clinical
      implications. Functioning epicardial patch leads should be incorporated in the
      defibrillation lead system if already present. If the LV patch is nonfunctioning,
      such as because of a lead fracture, the marked increase in DFT due to an inactive
      LV patch calls for thorough DFT testing during surgery and, in selected patients,
      may necessitate patch removal to produce an effective transvenous-based system.

PMID- 7586280
TI  - Epinephrine increases the severity of postresuscitation myocardial dysfunction.
AB  - BACKGROUND: Epinephrine has been the mainstay for cardiac resuscitation for more
      than 30 years. Its vasopressor effect by which it increases coronary perfusion
      pressure is likely to favor initial resuscitation. Its beta-adrenergic action,
      however, may have detrimental effects on postresuscitation myocardial function
      when administered before resuscitation because it increases myocardial oxygen
      consumption. In the present study, our focus was on postresuscitation effects of
      epinephrine when this adrenergic agent was administered during cardiopulmonary
      resuscitation. Postresuscitation myocardial functions were compared with those of
      a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined
      with a beta 1-adrenergic blocking agent, esmolol, and saline placebo. METHODS AND
      RESULTS: Ventricular fibrillation was induced in 40 Sprague-Dawley rats.
      Mechanical ventilation and precordial compression was initiated either 4 or 8
      minutes after the start of ventricular fibrillation. The adrenergic drug or
      saline placebo was administered as a bolus after 4 minutes of precordial
      compression. Defibrillation was attempted 4 minutes later. Left ventricular
      pressure, dP/dt40, and negative dP/dt were continuously measured for an interval
      of 240 minutes after successful cardiac resuscitation. Except for saline placebo,
      comparable increases in coronary perfusion pressure were observed after each drug
      intervention. The number of countershocks required for restoration of spontaneous
      circulation was significantly greater for epinephrine-treated animals (10 +/- 8)
      when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with
      animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01).
      After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and
      left ventricular end-diastolic pressure was significantly increased in each
      animal when compared with prearrest levels. However, the greatest impairment
      followed epinephrine, and this was associated with significantly greater heart
      rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours,
      whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated
      animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals
      that received a combination of epinephrine and esmolol survived for 35 +/- 11
      hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest
      was increased from 4 to 8 minutes, the severity of postresuscitation left
      ventricular dysfunction was magnified, but disproportionate decreases in
      postresuscitation survival were again observed with placebo and epinephrine when
      compared with alpha-adrenergic agonists. CONCLUSIONS: In an established rodent
      model after resuscitation following cardiac arrest, epinephrine significantly
      increased the severity of postresuscitation myocardial dysfunction and decreased
      duration of survival. More selective alpha-adrenergic agonist or blockade of beta
      1-adrenergic actions of epinephrine reduced postresuscitation myocardial
      impairment and prolonged survival.

PMID- 7586281
TI  - Effects of EMD 57033 on contraction and relaxation in isolated rabbit hearts.
AB  - BACKGROUND: Ca2+ sensitizers are reported to enhance contractility with modest
      effects on energy utilization. In the present study we assessed the effects of
      the relatively "pure" Ca2+ sensitizer EMD 57033 on mechanical performance and
      energy consumption in the beating heart. METHODS AND RESULTS: In 10 isolated, red
      blood cell-perfused rabbit hearts the effects of EMD 57033 (5.0 to 5.8 mumol/L)
      on left ventricular (LV) pressure and O2 consumption (VO2) were examined at heart
      rates of 100 and 150 beats per minute (bpm) and perfusate [Ca2+] ([Ca2+]o) of 2.5
      and 1.0 mmol/L (isovolumic contractions). LV developed pressure and maximum dP/dt
      increased, but less so at 150 bpm or 1.0 mmol/L [Ca2+]. End-diastolic pressure
      also increased, more so at 150 bpm or 1.0 mmol/L [Ca2+]o. EMD 57033 decreased
      time to peak isovolumic pressure (Tmax) and prolonged time to 50% pressure
      decline (T1/2). These changes were greater at slower heart rate or lower [Ca2+]o.
      The magnitude of increased VO2 with EMD 57033 was greater at 100 bpm than 150 bpm
      but unaffected by [Ca2+]o. We then investigated the influence of ejection on the
      response to EMD 57033 (n = 7). The increase in developed pressure with EMD 57033
      was greater for ejecting than isovolumic beats (25.5 +/- 10.2 versus 14.7 +/- 7.5
      mm Hg at 100 bpm, P < .01), while the increase in end-diastolic pressure was less
      (P = NS). The increase in VO2 was significantly greater for ejecting than
      isovolumic beats (0.027 +/- 0.013 versus 0.020 +/- 0.009 mL O2/beat per 100 g at
      100 bpm, P < .01). CONCLUSIONS: EMD 57033 enhances contractility and prolongs
      relaxation. Its effects are modulated by heart rate, [Ca2+]o, and contraction
      mode, with positive inotropic effects being more prominent for ejecting beats.

PMID- 7586282
TI  - Expression of renin-angiotensin system components in the heart, kidneys, and
      lungs of rats with experimental heart failure.
AB  - BACKGROUND: Chronic activation of the renin-angiotensin system (RAS) plays an
      important role in the pathogenesis of heart failure. Increasing evidence
      indicates that other than the circulating RAS, a local RAS exists in several
      tissues, including the heart. The present study was carried out to quantify
      cardiac, renal, and pulmonary mRNA levels of renin, angiotensin-converting enzyme
      (ACE), and types 1 and 2 angiotensin II receptors (AT-1 and AT-2), in rats with
      different severities of heart failure. METHODS AND RESULTS: Heart failure was
      induced by the creation of an aortocaval fistula below the renal arteries. Rats
      with aortocaval fistula either compensate and maintain a normal sodium balance or
      decompensate and develop severe sodium retention. Six days after placement of the
      aortocaval fistula, heart weight (normalized to body weight) increased 35% (P <
      .05) in compensated and 65% in decompensated rats compared with control rats.
      Plasma renin activity increased 45% (P < .05) in rats in sodium balance and 127%
      in sodium-retaining rats. Total RNA was extracted from the heart, kidneys, and
      lungs, followed by reverse transcription-quantitative polymerase chain reaction.
      Renin mRNA levels in the heart, after 40 cycles, increased 68% (P < .01) and 140%
      in rats with either compensated or decompensated heart failure, respectively.
      Renal renin-mRNA levels also increased 130% (P < .05) in decompensated and only
      52% (P < .05) in compensated animals. ACE-mRNA increased in a similar pattern in
      the heart but not in either the kidneys or lungs. Moreover, pulmonary, renal, and
      cardiac ACE immunoreactivity levels, assessed by Western blot analysis, showed
      the same trend. AT-1 receptor mRNA levels decreased 54% (P < .05) only in the
      myocardium of decompensated rats, whereas AT-2 receptor mRNA did not change in
      any tissue studied. CONCLUSIONS: The development of heart failure is associated
      with a remarkable increase in the expression of a local RAS in the heart, which
      may contribute to the pathogenesis of this clinical syndrome.

PMID- 7586286
TI  - Images in cardiovascular medicine. Calcific aortic stenosis and associated Lev's
      disease.

PMID- 7586285
TI  - ACE inhibitor use in patients with myocardial infarction. Summary of evidence
      from clinical trials.

PMID- 7586284
TI  - Effects of anterior communicating artery diameter on cerebral hemodynamics in
      internal carotid artery disease. A model study.
AB  - BACKGROUND: Collateral circulatory pathways are considered the primary
      determinant of cerebral hemodynamics in patients with obstructive lesions of the
      internal carotid arteries (ICaAs). However, the hemodynamic effects of the
      diameter of the anterior communicating artery (ACoA) have never been assessed
      quantitatively in humans. METHODS AND RESULTS: Two different mathematical models
      were used to simulate changes affecting blood pressures and flows in cerebral
      arteries as a function of ACoA diameter and ICaA stenoses or occlusions. Small
      changes in ACoA diameter were found to have marked hemodynamic effects when they
      occurred within the range of 0.4 to 1.6 mm, a situation observed in 80% of the
      cases. Outside this range, changes in ACoA diameter had no effect. Simulated
      pressure drops through a stenotic ICaA were consistent with those observed. They
      were found to depend on the degrees of the stenoses in both ICaAs and on ACoA
      diameter according to a simple equation. Pressure reserve in the middle and
      anterior cerebral arteries decreased to below the lower limit of autoregulation,
      despite a normal mean arterial blood pressure, when the arteries were distal to a
      unique 70% ICaA stenosis associated with a small-diameter ACoA or to a 50% ICaA
      stenosis associated with a contralateral ICaA occlusion and a large-diameter
      ACoA. Above these thresholds, the circle of Willis allowed for an almost complete
      global cerebral blood flow compensation that involved all the afferent and
      communicating vessels. CONCLUSIONS: ACoA diameter strongly modulates the effects
      of ICaA lesions on cerebral hemodynamics. Some proposals for endarterectomy
      indications can be derived from our study.

PMID- 7586283
TI  - Selective uptake of radiolabeled annexin V on acute porcine left atrial thrombi.
AB  - BACKGROUND: Annexin V is a human phospholipid binding protein that binds to
      activated platelets in vitro. We sought to determine the potential of this agent
      for imaging intracardiac thrombi in swine. METHODS AND RESULTS: Left atrial
      thrombi were formed by crush injury. In initial nonimaging experiments using
      intravenous 125I-labeled human annexin V, the mean thrombus/whole blood ratio was
      13.4 +/- 4.8 for the entire thrombus using well counting of resected specimens (n
      = 8). Using intravenously injected 99mTc-labeled human annexin V, the left atrial
      thrombus/blood ratio by well counting was similar (14.2 +/- 10.6 for the entire
      thrombus and 26.2 +/- 14.9 for the peak section) (n = 12). The ratio for a
      control protein, 125I-ovalbumin, was only 1.0 +/- 0.2. 99mTc tomographic imaging
      was positive (n = 10) or equivocal (n = 2) in all experiments with but negative
      in 10 controls without left atrial thrombi. By region-of-interest analysis of the
      tomographic images, the mean left atrial appendage/blood ratio at 2 hours in
      animals with a thrombus was 3.90 +/- 1.12 compared with 0.84 +/- 0.10 in closed
      chest controls and 1.01 +/- 0.23 in open chest controls (P < .001). CONCLUSIONS:
      We conclude that 99mTc-labeled human annexin V detects acute left atrial thrombi
      in vivo in swine. The combination of a new thrombus detection agent, annexin V,
      with a 99mTc label may allow in vivo imaging of thrombi in humans.

PMID- 7586287
TI  - Multiorgan failure after cardiac arrest in a 20-year-old man.

PMID- 7586288
TI  - ESVEM tells us what we don't know.

PMID- 7586289
TI  - Limitations of myocardial FDG studies.

PMID- 7586292
TI  - Fontan physiology.

PMID- 7586294
TI  - Metabolic complexities in cardiac imaging.

PMID- 7586290
TI  - Clinical and economic controversies in radionuclide assessment of myocardial
      viability.

PMID- 7586291
TI  - [18F]FDG in measuring myocardial glucose uptake.

PMID- 7586293
TI  - Chlamydia pneumoniae and acute arterial thrombotic disease.

PMID- 7586295
TI  - Time-dependent SCD risk during mountain sports changes with age.

PMID- 7586297
TI  - Large hearts in children. Biology or disease?

PMID- 7586296
TI  - Intravenous amiodarone. Another option in the acute management of sustained
      ventricular tachyarrhythmias.

PMID- 7586298
TI  - Identification of anomalous coronary arteries and their anatomic course by
      magnetic resonance coronary angiography.
AB  - BACKGROUND: Anomalous coronary arteries are a rare but recognized cause of
      myocardial ischemia and sudden death. Identification currently requires x-ray
      angiography, which may have difficulty defining the three-dimensional course of
      the anomalous vessel. Magnetic resonance coronary angiography (MRCA) has been
      shown to image coronary artery anatomy noninvasively. We hypothesize that MRCA
      may be useful in the identification of anomalous coronary arteries and their
      anatomic course. METHODS AND RESULTS: Sixteen patients (9 men, 7 women, age 44 to
      81 years) with anomalous aortic origins of the coronary arteries by conventional
      x-ray angiography underwent MRCA. Multiple images of the major epicardial
      coronary arteries were obtained by use of a breathhold, fat-suppressed, segmented
      k space, gradient-echo technique by investigators blinded to all patient data.
      Anomalous coronary artery pathology, by x-ray angiography, included right-sided
      left main coronary artery (n = 3), right-sided left circumflex artery (n = 6),
      separate left-sided left anterior descending and left circumflex arteries (n =
      2), left-sided right coronary artery (n = 4), and an anteriorly displaced right
      coronary artery (n = 1). MRCA correctly identified the anomalous coronary
      vessel(s) in 14 of 15 patients. In 1 patient, the anomalous vessel was
      incorrectly identified, and in 2 patients the course of the anomalous vessel was
      not clearly seen; one of these was a nondominant, anomalous right coronary
      artery. CONCLUSIONS: MRCA is a useful technique for the noninvasive
      identification of anomalous coronary arteries and their anatomic course.

PMID- 7586299
TI  - Magnetic resonance angiography of anomalous coronary arteries. A new gold
      standard for delineating the proximal course?
AB  - BACKGROUND: The clinical significance of anomalously originating coronary
      arteries depends on their proximal course. Diagnosis of this course by
      conventional x-ray coronary angiography alone may be equivocal. We postulated
      that with fast magnetic resonance (MR) angiography, accurate detection of
      anomalous coronary arteries and unambiguous delineation of their proximal course
      is feasible. METHODS AND RESULTS: In a selected group of 38 patients, 19 of them
      having an anomalously originating coronary artery, a fast MR angiographic
      technique was used to study the proximal coronary anatomy. Blinded analysis of
      randomly ordered MR studies was performed independently by two observers. Both
      origin and proximal course of the coronary arteries were defined. Two
      cardiologists reviewed all x-ray coronary angiograms. After the separate
      analyses, a final consensus result was defined for each patient. In 37 patients,
      successful MR coronary angiography could be performed. Interobserver agreement
      for determining both origin and proximal course was 100%. An x-ray coronary
      angiogram was available in 36 patients. In 3 patients (all with an anomalous left
      main coronary artery originating from the right aortic sinus), there was
      disagreement about the proximal course between the results of MR and x-ray
      coronary angiography. Review of these cases demonstrated that MR angiography had
      unambiguously visualized the proximal coronary artery course, whereas the results
      of x-ray angiography had been equivocal. Thus, sensitivity and specificity for
      detecting anomalous coronary arteries and delineating their proximal course were
      100%. CONCLUSIONS: These data suggest that fast MR angiography is highly accurate
      in determining the origin and delineating the proximal course of anomalous
      coronary arteries, even in those cases in which x-ray coronary angiographic
      diagnosis is difficult or even erroneous.

PMID- 7586300
TI  - Hyperlipidemia and coronary disease. Correction of the increased thrombogenic
      potential with cholesterol reduction.
AB  - BACKGROUND: Hypercholesterolemia is a risk factor for coronary disease, and
      platelet reactivity is increased with hypercholesterolemia, suggesting a
      prethrombotic risk. The aim of this study was to measure mural platelet thrombus
      formation on an injured arterial wall in a model simulating vessel stenosis and
      plaque rupture in hypercholesterolemic coronary disease patients before and after
      cholesterol reduction. METHODS AND RESULTS: Thirty-two patients with stable
      coronary disease were studied. Platelet thrombus formation and serum lipids were
      measured in 16 hypercholesterolemic patients (cholesterol > 5.2 mmol/L) before
      and after a mean of 2.5 months of pravastatin therapy (40 mg/d) and in 16
      normocholesterolemic control patients. Thrombus formation was assessed by
      exposing porcine aortic media to the patient's flowing venous blood for 3 minutes
      at a shear rate of 754 or 2546 s-1 at 37 degrees C in an ex vivo superfusion
      chamber. Quantitative morphometric platelet thrombus formation at baseline was
      higher in the hypercholesterolemic patients at both the high and low shear rates:
      4.8 +/- 1.0 and 3.3 +/- 0.7 micron 2/mm, respectively, compared with
      normocholesterolemic patients: 2.1 +/- 0.5 and 1.6 +/- 0.4 micron 2/mm (both P <
      .05). In the hypercholesterolemic patients, pravastatin decreased total
      cholesterol from 6.5 +/- 0.2 to 4.5 +/- 0.2 mmol/L and LDL cholesterol from 4.5
      +/- 0.2 to 2.8 +/- 0.1 mmol/L (both P < .05). Platelet thrombus formation at high
      and low shear rates decreased to 2.0 +/- 0.3 and 1.3 +/- 0.3 micron 2/mm,
      respectively (both P < .05). CONCLUSIONS: Thus, hypercholesterolemia is
      associated with an enhanced platelet thrombus formation on an injured artery,
      increasing the propensity for acute thrombosis. Platelet thrombus formation at
      both high and low shear rates decreased as total and LDL cholesterol levels were
      reduced with pravastatin. Cholesterol lowering may therefore reduce the risk of
      acute coronary events in part by reducing the thrombogenic risk.

PMID- 7586301
TI  - Prospective study of shift work and risk of coronary heart disease in women.
AB  - BACKGROUND: The purpose of this study was to examine prospectively the relation
      of shift work to risk of coronary heart disease (CHD) in a cohort of women.
      METHODS AND RESULTS: An ongoing prospective cohort of US female nurses, in whom
      we assessed (in 1988) the total number of years during which they worked rotating
      night shifts (at least three nights per month in addition to day and evening
      shifts), included 79,109 women, 42 to 67 years old in 1988, who were free of
      diagnosed CHD and stroke. Incident CHD was defined as nonfatal myocardial
      infarction and fatal CHD. During 4 years of follow-up (1988 to 1992), 292 cases
      of incident CHD (248 nonfatal myocardial infarction and 44 fatal CHD) occurred.
      The age-adjusted relative risk of CHD was 1.38 (95% CI, 1.08 to 1.76) in women
      who reported ever doing shift work compared with those who had never done so. The
      excess risk persisted after adjustment for cigarette smoking and a variety of
      other cardiovascular risk factors. Compared with women who had never done shift
      work, the multivariate adjusted relative risks of CHD were 1.21 (95% CI, 0.92 to
      1.59) among women reporting less than 6 years and 1.51 (95% CI, 1.12 to 2.03)
      among those reporting 6 or more years of rotating night shifts. CONCLUSIONS:
      These data are compatible with the possibility that 6 or more years of shift work
      may increase the risk of CHD in women.

PMID- 7586302
TI  - Fractional flow reserve. A useful index to evaluate the influence of an
      epicardial coronary stenosis on myocardial blood flow.
AB  - BACKGROUND: Fractional flow reserve (FFR), defined as the ratio of maximum flow
      in the presence of a stenosis to normal maximum flow, is a lesion-specific index
      of stenosis severity that can be calculated by simultaneous measurement of mean
      arterial, distal coronary, and central venous pressure (Pa, Pd, and Pv,
      respectively), during pharmacological vasodilation. The aims of this study were
      to define ranges of FFR values, whether associated with inducible ischemia or
      not, and to investigate FFR in normal coronary arteries. METHODS AND RESULTS: In
      60 patients accepted for percutaneous transluminal coronary angioplasty (PTCA) of
      single-vessel disease, with a positive exercise test (ET) < 24 hours before PTCA,
      FFR was determined during adenosine-induced hyperemia just before and 15 minutes
      after angioplasty. Pa was measured by the guiding catheter, Pd by an 0.018-in
      fiber-optic pressure-monitoring wire, and Pv, by a multipurpose catheter. The ET
      was repeated after 5 to 7 days, and only if this second ET had reverted to normal
      was the pre-PTCA value of FFR definitely considered to be associated with
      inducible ischemia and the post-PTCA value not. Myocardial FFR (FFRmyo) increased
      from 0.53 +/- 0.15 before PTCA to 0.88 +/- 0.07 after PTCA. Coronary FFR
      increased from 0.38 +/- 0.19 to 0.83 +/- 0.12. In all patients, values of FFRmyo
      definitely associated with ischemia were < or = 0.74, whereas all except two
      values not associated with inducible ischemia exceeded 0.74. Moreover, FFRmyo in
      18 coronary arteries in 5 normal patients equaled 0.98 +/- 0.03. CONCLUSIONS: A
      value of FFRmyo of 0.74 reliably discriminates coronary stenosis, whether
      associated with inducible ischemia or not. Therefore, FFRmyo is a useful index to
      determine the functional significance of an epicardial coronary stenosis and may
      facilitate clinical decision making in patients with an equivocal coronary
      stenosis.

PMID- 7586303
TI  - Effect of thromboxane A2 blockade on clinical outcome and restenosis after
      successful coronary angioplasty. Multi-Hospital Eastern Atlantic Restenosis Trial
      (M-HEART II)
AB  - BACKGROUND: Antithromboxane therapy with aspirin reduces acute procedural
      complications of coronary angioplasty (PTCA) but has not been shown to prevent
      restenosis. The effect of chronic aspirin therapy on long-term clinical events
      after PTCA is unknown, and the utility of more specific antithromboxane agents is
      uncertain. The goal of this study was to assess the effects of aspirin (a
      nonselective inhibitor of thromboxane A2 synthesis) and sulotroban (a selective
      blocker of the thromboxane A2 receptor) on late clinical events and restenosis
      after PTCA. METHODS AND RESULTS: Patients (n = 752) were randomly assigned to
      aspirin (325 mg daily), sulotroban (800 mg QID), or placebo, started within 6
      hours before PTCA and continued for 6 months. The primary outcome was clinical
      failure at 6 months after successful PTCA, defined as (1) death, (2) myocardial
      infarction, or (3) restenosis associated with recurrent angina or need for repeat
      revascularization. Neither active treatment differed significantly from placebo
      in the rate of angiographic restenosis: 39% (73 of 188) in the aspirin-assigned
      group, 53% (100 of 189) in the sulotroban group, and 43% (85 of 196) in the
      placebo group. In contrast, aspirin therapy significantly improved clinical
      outcome in comparison to placebo (P = .046) and sulotroban (P = .006). Clinical
      failure occurred in 30% (49 of 162) of the aspirin group, 44% (73 of 166) of the
      sulotroban group, and 41% (71 of 175) of the placebo group. Myocardial infarction
      was significantly reduced by antithromboxane therapy: 1.2% in the aspirin group,
      1.8% in the sulotroban group, and 5.7% in the placebo group (P = .030).
      CONCLUSIONS: Thromboxane A2 blockade protects against late ischemic events after
      angioplasty even though angiographic restenosis is not significantly reduced.
      While both aspirin and sulotroban prevent the occurrence of myocardial
      infarction, overall clinical outcome appears superior for aspirin compared with
      sulotroban. Therefore, aspirin should be continued for at least 6 months after
      coronary angioplasty.

PMID- 7586304
TI  - Circadian variation in coronary tone in patients with stable angina. Protective
      role of the endothelium.
AB  - BACKGROUND: Coronary endothelium plays a key role in the regulation of coronary
      tone, platelet adhesion, and aggregation, which are important factors in
      triggering acute cardiovascular events. However, its role in modulating the
      effects of circadian variations on coronary tone is not known. METHODS AND
      RESULTS: Responses of 72 nonstenotic coronary segments to acetylcholine and
      nitroglycerin were measured in 12 patients with chronic stable angina at 6 AM and
      1 PM. After baseline angiography, three infusions of acetylcholine (10(-6), 10(
      5), and 10(-4) mol/L) were administered selectively into the left coronary
      artery, followed by nitroglycerin. Diameters (in millimeters) of proximal,
      middle, and distal segments were measured by quantitative techniques. Forty-seven
      segments showed a constrictor response to acetylcholine (group 1, dysfunctional
      endothelium), and 25 other segments showed a dilator response (group 2, normally
      functioning endothelium). In group 1, the constrictor response to acetylcholine
      was significantly greater in the morning than in the afternoon (23 +/- 3% and 10
      +/- 1%, mean +/- SEM, respectively; P < .001), and the dilator response to
      nitroglycerin was also significantly greater in the morning than in the afternoon
      (19 +/- 2% and 11 +/- 2%; P < .01). In group 2, the dilator response to
      acetylcholine did not differ significantly between the morning and afternoon (22
      +/- 3% and 17 +/- 2%, respectively; P = NS), and the dilator response to
      nitroglycerin was also similar at both times of the day (30 +/- 3% and 28 +/- 4%,
      respectively; P = NS). CONCLUSIONS: Coronary segments with dysfunctional
      endothelium exhibit an early morning exaggeration in vasomotor activity, whereas
      segments with normally functioning endothelium do not show circadian variations.
      This suggests a potential protective role for the endothelium in modulating
      variations in coronary tone that may contribute to increased incidence of
      cardiovascular events in the early morning hours.

PMID- 7586305
TI  - Sympathetic activation and loss of reflex sympathetic control in mild congestive
      heart failure.
AB  - BACKGROUND: Baroreflex control of sympathetic activity is impaired in severe
      congestive heart failure (CHF), probably causing the marked sympathetic
      activation typical of this condition. Little information exists, however, as to
      whether baroreflex impairment and related sympathetic activation also occur in
      mild CHF. METHODS AND RESULTS: We studied 19 patients (age, 57.5 +/- 2.2 years,
      mean +/- SEM) with CHF in New York Heart Association (NYHA) class III or IV and
      with a marked reduction in left ventricular ejection fraction (LVEF, 30.1 +/-
      1.5% from echocardiography) and 17 age-matched patients with CHF in NYHA class I
      or II and with an only slightly reduced LVEF (44.9 +/- 3.3%) that never was <
      40%. Seventeen age-matched healthy subjects served as control subjects. Primary
      measurements included beat-to-beat arterial blood pressure (with the Finapres
      technique), heart rate (from ECG), and postganglionic muscle sympathetic nerve
      activity (MSNA, from microneurography at the peroneal nerve). Measurements were
      performed at baseline and during baroreceptor stimulation (intravenous
      phenylephrine infusion), baroreceptor deactivation (intravenous nitroprusside
      infusion), and cold-pressor test. Baseline blood pressure was similar in the
      three groups, whereas heart rate was progressively greater from control subjects
      to patients with mild and severe CHF, MSNA (bursts per 100 heart beats) increased
      significantly and markedly from control subjects to patients with mild and severe
      CHF (47.1 +/- 2.9 versus 64.4 +/- 6.2 and 82.1 +/- 3.4, P < .05 and P < .01,
      respectively). Heart rate and MSNA were progressively reduced by phenylephrine
      infusion and progressively increased by nitroprusside infusion. Compared with
      control subjects, the responses were strikingly impaired in severe CHF patients,
      but a marked impairment also was seen in mild CHF patients. On average,
      baroreflex sensitivity in mild CHF patients was reduced by 59.1 +/- 5.5% (MSNA)
      and 64.8 +/- 4.8% (heart rate). In contrast, reflex responses to the cold-pressor
      test were similar in the three groups. CONCLUSIONS: These results demonstrate
      that in mild CHF patients the baroreceptor inhibitor influence on heart rate and
      MSNA is already markedly impaired. This impairment may be responsible for the
      early sympathetic activation that occurs in the course of CHF.

PMID- 7586306
TI  - Endothelial control of arterial distensibility is impaired in chronic heart
      failure.
AB  - BACKGROUND: Vascular tone is a determinant of conduit artery distensibility. The
      aim of this study was to establish whether endothelium-derived relaxing factor
      (EDRF) influences the distensibility of conduit arteries and whether endothelium
      mediated increases in distensibility are impaired in chronic heart failure (CHF).
      METHODS AND RESULTS: Conduit artery distensibility was measured by two methods in
      healthy subjects and in nine patients with CHF caused by dilated cardiomyopathy.
      In the first method, pulse-wave velocity (PWV) was measured in the right common
      iliac artery at rest and during local infusions of acetylcholine (10(-7) to 10(
      5) mol/L) or adenosine (2 x 10(-7) to 2 x 10(-5) mol/L), with correction for
      systemic effects. Acetylcholine induced concentration-dependent local reductions
      of PWV in healthy subjects (-5%, -15%, and -26%) but not in CHF patients (3%, 1%,
      -4%, P < .01), whereas adenosine induced similar reductions of PWV in healthy
      subjects and CHF patients. In the second method, brachial artery diameter, blood
      flow, and blood pressure were measured noninvasively by high-resolution
      ultrasound, continuous-wave Doppler, and photoplethysmography during reactive
      hyperemia in the hand and after sublingual glyceryl trinitrate (GTN, 400
      micrograms). Hyperemic flow, similar in healthy subjects and CHF patients, was
      associated with increases in diameter and distensibility in healthy subjects
      (8.8% and 18.4%, respectively) but not in CHF patients (0.3% and -4.5%), whereas
      GTN induced similar effects in healthy subjects and CHF patients. CONCLUSIONS:
      These data indicate that conduit artery distensibility is increased by
      acetylcholine and increased blood flow in healthy subjects but not in CHF
      patients, whereas the effects of adenosine and GTN on distensibility are
      preserved in CHF patients. This implies that EDRF-mediated increases in
      distensibility are impaired in CHF patients, thus adding to cardiac work.

PMID- 7586307
TI  - Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake
      and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum from dilated
      cardiomyopathy patients compared with patients with nonfailing hearts.
AB  - BACKGROUND: The aim of the present study was to investigate whether Ca2+ uptake
      into the sarcoplasmic reticulum (SR) is altered in failing human myocardium
      resulting from dilated cardiomyopathy. METHODS AND RESULTS: Ca(2+)-ATPase (SERCA
      II) activity and Ca(2+)-dependent 45Ca2+ uptake (oxalate supported, steady state)
      in isolated vesicles from the SR (VSR) and in crude membrane preparations (CSR)
      (free Ca2+, 0.01 to 100 mumol/L) from nonfailing (donor hearts, n = 13) and
      terminally failing (heart transplants, dilated cardiomyopathy, n = 17) human
      myocardium were studied. In the same hearts, protein levels (Western blot
      analysis) and mRNA levels (Northern blot analysis) of SERCA II and phospholamban
      were measured. Increasing concentrations of Ca2+ were followed by an increased
      Ca(2+)-ATPase activity and Ca2+ uptake. Ca2+ uptake activity and Ca(2+)-ATPase
      activity in CSR preparations from failing myocardium were significantly reduced
      compared with nonfailing hearts (Ca(2+)-ATPase, 163 +/- 8 and 125 +/- 7 nmol
      ATP/mg protein per minute for nonfailing tissue and failing tissue in New York
      Heart Association [NYHA] class IV, respectively; Ca2+ uptake, 7.1 +/- 0.8 and 3.5
      +/- 0.3 nmol/mg protein per minute in CSR from nonfailing and NYHA class IV
      hearts, respectively P < .05). In contrast, no significant difference was
      measured in VSR. In the same preparations (CSR and VSR), both SERCA II and
      phospholamban levels (Western blot technique with monoclonal antibodies) were
      unchanged in failing compared with nonfailing tissue. mRNA expression relative to
      GAPDH mRNA for SERCA IIa and for phospholamban was significantly reduced in
      failing human myocardium (P < .05). CONCLUSIONS: These findings provide evidence
      that in failing human myocardium caused by dilated cardiomyopathy, protein levels
      of SERCA II and phospholamban are unchanged even though mRNA levels for SERCA II
      and phospholamban and the SERCA II function are reduced compared with nonfailing
      myocardium.

PMID- 7586308
TI  - Pericardial effusion in AIDS. Incidence and survival.
AB  - BACKGROUND: Although pericardial effusion is known to be common among patients
      infected with HIV, the incidence of pericardial effusion and its relation to
      survival have never been described. METHODS AND RESULTS: To evaluate the
      incidence of pericardial effusion and its relation to mortality in HIV-positive
      subjects, 601 echocardiograms were performed on 231 subjects recruited over a 5
      year period (inception cohort: 59 subjects with asymptomatic HIV, 62 subjects
      with AIDS-related complex, and 74 subjects with AIDS; 21 HIV-negative healthy gay
      men; and 15 subjects with non-HIV end-stage medical illness). Echocardiograms
      were performed every 3 to 6 months (82% had follow-up studies). Sixteen subjects
      were diagnosed with effusions (prevalence of effusion for AIDS subjects entering
      the study was 5%). Thirteen subjects developed effusions during follow-up; 12 of
      these were subjects with AIDS (incidence, 11%/y). The majority of effusions (80%)
      were small and asymptomatic. The survival of AIDS subjects with effusions was
      significantly shorter (36% at 6 months) than survival for AIDS subjects without
      effusions (93% at 6 months). This shortened survival remained significant
      (relative risk, 2.2, P = .01) after adjustment for lead time bias and was
      independent of CD4 count and albumin level. CONCLUSIONS: There is a high
      incidence of pericardial effusion in patients with AIDS, and the presence of an
      effusion is associated with shortened survival. The development of an effusion in
      the setting of HIV infection suggests end-stage HIV disease (AIDS).

PMID- 7586309
TI  - Patient factors associated with strut fracture in Bjork-Shiley 60 degrees convexo
      concave heart valves.
AB  - BACKGROUND: Previously established predictors of outlet strut fracture in Bjork
      Shiley convexo-concave (CC) valves include larger valve size, larger opening
      angle (70 degrees versus 60 degrees), younger age at implant, and date of
      manufacture. We sought to identify patient characteristics that might be
      predictive of strut fracture and to refine the estimates associated with
      previously identified predictors. METHODS AND RESULTS: We conducted a case
      control study of CC60 degrees valves implanted in the United States and Canada
      and manufactured between January 1, 1979, and March 31, 1984. Cases included all
      valves with verified outlet strut fractures reported to the manufacturer from
      January 1979 through January 1992. Up to 10 controls were selected for each case.
      Control valves were matched according to implanting surgeon and were required to
      have been functioning at least as long as their matched case valves. Case and
      control medical records were reviewed for information on patient medical history
      before the valve implant. There were 96 case and 634 control valves for which
      clinical data were available. Patient age and valve size and implant position
      were confirmed as important determinants of fracture. There was a strong inverse
      gradient of risk with age. The risk of fracture was 42% lower for each 10-year
      increment of patient age at time of implant. Large mitral valves were at greatest
      risk of strut fracture, with the largest mitral valves (33 mm) estimated to be 33
      times more likely to fracture than the smallest (21 to 25 mm) aortic valves. Date
      of manufacture was also associated with risk; valves welded from mid-1981 through
      March 1984 were more likely to fracture than those manufactured in 1979 and 1980.
      Body surface area < 1.5 m2 was associated with 1/16 the risk of body surface area
      > or = 2.0 m2. No other patient factor was strongly associated with the risk of
      strut fracture. CONCLUSIONS: Few patient features identifiable in the implant
      record are predictive of strut fracture. Our analysis supports previous work in
      identifying valve size, patient age, and date of manufacture as predictors of
      fracture and adds body surface area. A number of these associations suggest that
      conditions associated with higher cardiac output may also place patients at
      increased risk.

PMID- 7586311
TI  - Effect of lean body mass, fat mass, blood pressure, and sexual maturation on left
      ventricular mass in children and adolescents. Statistical, biological, and
      clinical significance.
AB  - BACKGROUND: Left ventricular hypertrophy has been established as an independent
      risk factor for the development of cardiovascular morbidity and mortality. It is
      clear that left ventricular mass increases during childhood and adolescence with
      body growth. The extent to which other factors, such as obesity, stage of sexual
      maturation, and level of blood pressure, determine left ventricular mass has been
      controversial. METHODS AND RESULTS: The study was a cross-sectional evaluation of
      the relationship of left ventricular mass determined by echocardiography with
      lean body mass and fat mass determined by dual-energy x-ray absorptiometry, which
      is the most valid and reliable method for determination of body composition in
      children and adolescents. The relationship of left ventricular mass with the
      stage of sexual maturation and with systolic and diastolic blood pressure was
      also evaluated. Two hundred one subjects (105 boys, 96 girls; 103 white and 98
      black) 6 to 17 years old were studied. Age (r = .72), height (r = .81), weight (r
      = .84), body surface area (r = .87), sexual maturation (r = .75), lean body mass
      (r = .86), fat mass (r = .54), systolic BP (r = .58), and diastolic BP (r = .48)
      were all univariate correlates of left ventricular mass. In a multiple regression
      analysis, only lean body mass, fat mass, and systolic blood pressure were
      statistically significant independent correlates of left ventricular mass. Lean
      body mass alone explained 75% of the variance of left ventricular mass, whereas
      fat mass and systolic blood pressure explained only 1.5% and 0.5% of the
      variance, respectively. Lean body mass was the strongest determinant of left
      ventricular mass in all four race-sex groups. CONCLUSIONS: This study provides an
      opportunity to separate the effects on left ventricular mass of lean body mass
      resulting from linear growth from those of fat mass resulting from obesity. Lean
      body mass, fat mass, and systolic blood pressure all have a statistically
      significant independent association with left ventricular mass, suggesting that
      all three play an important biological role in determining left ventricular mass.
      However, fat mass and systolic blood pressure have only a small impact on left
      ventricular mass. This indicates that fat mass and blood pressure would be
      expected to be of only minor clinical importance in determining left ventricular
      mass in normal children and adolescents.

PMID- 7586310
TI  - Plasma HDL cholesterol, triglycerides, and adiposity. A quantitative genetic test
      of the conjoint trait hypothesis in the San Antonio Family Heart Study.
AB  - BACKGROUND: The conjoint trait hypothesis proposes that combined low HDL
      cholesterol (HDL-C) and high triglyceride (TG) levels represent a single,
      inherited phenotype that adiposity may influence in an unspecified manner. We
      conducted formal statistical genetic tests of the conjoint trait hypothesis and
      the relation of the conjoint trait to adiposity using data for 569 subjects in 25
      pedigrees from the San Antonio Family Heart Study. METHODS AND RESULTS: We
      conducted multivariate genetic analyses to detect the effects of genes and
      environmental factors on variation in plasma concentrations of HDL-C and TG, fat
      mass (as percent body weight [FM%], determined by bioelectric impedance), and
      body mass index (BMI). We used maximum-likelihood methods to simultaneously
      estimate the phenotypic means and SDs, heritabilities (h2), effects of sex, age
      by-sex, eight dietary and medical covariates, and genetic and environmental
      correlations. Likelihood ratio tests disclosed significant heritabilities (P <
      .001) for all traits (h2HDL-C = 0.55, h2TG = 0.53, h2FM% = 0.37, h2BMI = 0.44)
      but significant genetic correlations (P < .001), indicating pleiotropy, between
      two trait pairs only: HDL-C and TG (PG = -0.52) and fat mass and BMI (PG = 0.86).
      We obtained significant environmental correlations between all trait pairs except
      HDL-C and BMI (P > .05). CONCLUSIONS: Both shared genes (pleiotropy) and shared
      environmental factors contribute to the commonly observed inverse phenotypic
      association between plasma levels of HDL-C and TG. Rather than low HDL-C and high
      TG being a single, genetically transmissible entity, it is the inverse relation
      between these two phenotypes throughout their normal ranges of variation as well
      as at the extremes that is influenced by shared genes and shared environments.
      However, common environmental factors, not shared genes, account for reported
      associations of plasma HDL-C and TG levels with measures of adiposity.

PMID- 7586312
TI  - Randomized, double-blind comparison of intravenous amiodarone and bretylium in
      the treatment of patients with recurrent, hemodynamically destabilizing
      ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter
      Investigators Group.
AB  - BACKGROUND: After several days of loading, oral amiodarone, a class III
      antiarrhythmic, is highly effective in controlling ventricular tachyarrhythmias;
      however, the delay in onset of activity is not acceptable in patients with
      immediately life-threatening arrhythmias. Therefore, an intravenous form of
      therapy is advantageous. This study was designed to compare the safety and
      efficacy of a high and a low dose of intravenous amiodarone with bretylium, the
      only approved class III antiarrhythmic agent. METHODS AND RESULTS: A total of 302
      patients with refractory, hemodynamically destabilizing ventricular tachycardia
      or ventricular fibrillation were enrolled in this double-blind trial at 82
      medical centers in the United States. They were randomly assigned to therapy with
      intravenous bretylium (4.7 g) or intravenous amiodarone administered in a high
      dose (1.8 g) or a low dose (0.2 g). The primary analysis, arrhythmia event rate
      during the first 48 hours of therapy, showed comparable efficacy between the
      bretylium group and the high-dose (1000 mg/24 h) amiodarone group that was
      greater than that of the low-dose (125 mg/24 h) amiodarone group. Similar results
      were obtained in the secondary analyses of time to first event and the proportion
      of patients requiring supplemental infusions. Overall mortality in the 48-hour
      double-blind period was 13.6% and was not significantly different among the three
      treatment groups. Significantly more patients treated with bretylium had
      hypotension compared with the two amiodarone groups. More patients remained on
      the 1000-mg amiodarone regimen than on the other regimens. CONCLUSIONS: Bretylium
      and amiodarone appear to have comparable efficacies for the treatment of highly
      malignant ventricular arrhythmias. Bretylium use, however, may be limited by a
      high incidence of hypotension.

PMID- 7586314
TI  - Influence of the implantable cardioverter/defibrillator on sudden death and total
      mortality in patients evaluated for cardiac transplantation.
AB  - BACKGROUND: Implantable cardioverter/defibrillators (ICDs) may reduce sudden
      tachyarrhythmic death in patients with severe left ventricular dysfunction. It is
      uncertain whether this improves survival, particularly in patients awaiting
      cardiac transplantation. METHODS AND RESULTS: The effect of treatment for
      spontaneous ventricular arrhythmias (ICD [n = 59], antiarrhythmic drugs [n = 53],
      or no antiarrhythmic treatment [n = 179]) on total mortality and mode of cardiac
      death was analyzed in 291 consecutive patients evaluated for cardiac
      transplantation between January 1986 and January 1995. There were 109 deaths
      (37.4%) (63 [21.6%] sudden, 40 [13.7%] nonsudden, and 6 [2.1%] noncardiac) during
      mean follow-up of 15 months (range, 1 to 118 months). Baseline clinical
      variables, medical therapies for heart failure, and actuarial rates of
      transplantation were similar between treatment groups. Kaplan-Meier sudden death
      rates were lowest in the ICD group, intermediate in the no antiarrhythmic
      treatment group, and highest in the drug treatment group throughout follow-up (12
      month sudden death rates, 9.2%, 16.0%, and 34.7%, respectively; P = .004). Total
      mortality and nonsudden death rates did not differ. Cox proportional-hazards
      model revealed that antiarrhythmic drug treatment was associated with sudden
      death (relative risk, 2.1; 95% CI, 1.04 to 3.39; P = .04) and ICD was associated
      with nonsudden death (relative risk, 2.26; 95% CI, 1.12 to 4.62; P = .02).
      CONCLUSIONS: Sudden death rates were lowest in patients treated with ICDs
      compared with drug treatment or no antiarrhythmic treatment. However, although
      ICDs reduced sudden death in selected high-risk patients with severe left
      ventricular dysfunction, the effect on long-term survival was limited,
      principally by high nonsudden death rates.

PMID- 7586313
TI  - Dose-ranging study of intravenous amiodarone in patients with life-threatening
      ventricular tachyarrhythmias. The Intravenous Amiodarone Multicenter
      Investigators Group.
AB  - BACKGROUND: Oral amiodarone effectively suppresses ventricular arrhythmias;
      however, full activity may take days or weeks. In patients with frequent, life
      threatening ventricular arrhythmias, this delay is not acceptable. Thus, in these
      patients, the speed and dosing accuracy of an intravenous formulation would be
      beneficial. The goal of this study was to demonstrate the efficacy of intravenous
      amiodarone in patients with refractory, recurrent hemodynamically destabilizing
      ventricular tachycardia or ventricular fibrillation by determining a dose
      response among three regimens. METHODS AND RESULTS: A total of 342 patients were
      enrolled at 46 medical centers in the United States. Patients received one of
      three randomized, double-blind dose regimens delivering 125, 500, or 1000 mg
      during the first 24 hours. Supplemental infusions (150 mg) of intravenous
      amiodarone could be given to treat breakthrough ventricular arrhythmias. The key
      efficacy end points were the arrhythmia event rate, time to first arrhythmic
      event, and number of supplemental infusions administered. The event rate
      decreased with increasing doses: median values were 0.07, 0.04, and 0.02 events
      per hour for the 125-, 500-, and 1000-mg dose groups, respectively, representing
      a significant decrease from baseline event rates (P = .043), and approached
      significance in the overall test for trend (P = .067). There was a significant
      dose-related increase in the time to first event (trend test P = .025) and a
      significant dose-related decrease in the number of supplemental boluses per hour
      (trend test P = .043). Hypotension was the most common (26%) treatment-emergent
      adverse event during intravenous amiodarone therapy; there was no dose-response
      relationship. Seventy-eight percent of the patients survived to at least 48
      hours. CONCLUSIONS: Intravenous amiodarone is effective for the treatment of
      recurrent, life-threatening ventricular tachyarrhythmias.

PMID- 7586315
TI  - Prolongation of RV-PA conduit life span by percutaneous stent implantation.
      Intermediate-term results.
AB  - BACKGROUND: Right ventricle-to-pulmonary artery (RV-PA) homografts and
      bioprosthetic conduits are commonly used to palliate various types of complex
      congenital heart disease. These conduits frequently develop progressive
      obstruction and require surgical replacement. This report reviews our experience
      implanting balloon-expandable stents to relieve conduit obstruction and delay
      reoperation. METHODS AND RESULTS: A retrospective review identified 44 patients
      who underwent placement of 48 stents in obstructed RV-PA conduits. Median patient
      age was 6.9 years (range, 7 months to 30 years), and median follow-up time was
      14.2 months (range, 0 to 48 months). Stent implantation initially decreased the
      RV-PA pressure gradient from 61.0 +/- 16.9 to 29.7 +/- 11.9 mm Hg (P < or = .001)
      and the right ventricular-to-systemic arterial pressure ratio from 0.92 +/- 0.17
      to 0.63 +/- 0.20 (P < or = .001). The diameter of the stenotic region expanded
      from 9.3 +/- 3.5 to 12.3 +/- 3.3 mm in the anteroposterior view (P < or = .001)
      and from 6.6 +/- 2.9 to 10.9 +/- 2.5 mm in the lateral view (P < or = .001).
      During the follow-up period, 2 patients had their stents redilated, 7 had
      additional conduit stents deployed, and 14 underwent surgical replacement of
      their conduits. Actuarial freedom from conduit reoperation was 65% at 30 months
      postprocedure. Seven patients were found to have fractured stents on follow-up,
      suggesting an important role for external compressive forces in conduit failure.
      Recatheterization in 16 patients a median of 11.8 months (3 to 48 months)
      postprocedure demonstrated hemodynamic evidence of recurrent obstruction despite
      sustained enlargement at the previously stented sites. Complications included
      stent displacement (n = 1), bacterial endocarditis (n = 1), and false aneurysm
      formation (n = 1). One patient died awaiting conduit replacement surgery.
      CONCLUSIONS: Stent implantation in obstructed RV-PA conduits results in
      significant immediate hemodynamic and angiographic improvement. In a subgroup of
      patients, the procedure prolongs conduit life span by several years and increases
      the interval between conduit reoperations. Recurrent obstruction is caused by
      external compression and progressive stenosis outside the stented region.

PMID- 7586316
TI  - Vascular smooth muscle cells of H-2Kb-tsA58 transgenic mice. Characterization of
      cell lines with distinct properties.
AB  - BACKGROUND: The vascular wall is composed of at least two different populations
      of smooth muscle cells that are distinct in their structure and protein
      composition. According to the developmental stage of tissue taken for culture,
      the ratio between cells of epithelioid phenotype and spindle-shaped cells is
      variable. In particular, the epithelioid cells display characteristic features
      associated with immaturity. Because their increased appearance can be observed in
      endothelial denudation, the represent a dedifferentiated, proliferative smooth
      muscle cell type with a repair function in vascular injury. METHODS AND RESULTS:
      To investigate this cellular heterogeneity, we established vascular smooth muscle
      cell lines from H-2Kb-tsA58 transgenic mice. Due to temperature-sensitive
      expression of the SV 40 large T-antigen in cells derived from this mouse strain,
      our smooth muscle lines were conditionally immortalized from the onset of their
      life in culture. Thus, we were able to clone cell lines representing the two
      different phenotypes described so far. Epithelioid cells derived from newborn
      animals are characterized by their expression of cytokeratins and the development
      of tight junctional complexes. Spindle-shaped cells, which could be isolated from
      newborn or adult animals, corresponded in phenotype and protein expression to
      smooth muscle cell lines established previously. CONCLUSIONS: The special
      properties of vascular smooth muscle cells of the epithelioid phenotype suggest
      an endothelial replacement function in the course of injury to the vascular wall.

PMID- 7586317
TI  - Induction of 15-lipoxygenase mRNA and protein in early atherosclerotic lesions.
AB  - BACKGROUND: 15-Lipoxygenase (15-LO) may be involved in atherogenesis and in
      oxidative modification of LDL. In this study, we investigated 15-LO expression in
      developing atherosclerotic lesions and verified the exact type of the
      atherosclerosis-associated LO at the nucleotide level. METHODS AND RESULTS:
      Quantitative reverse transcription-polymerase chain reaction, in situ
      hybridization, and immunocytochemistry were used in two models of experimental
      atherosclerosis. New Zealand White rabbits were given a 1% cholesterol diet for 0
      (control group), 3, 6, or 14 weeks. 15-LO mRNA was undetectable in the aortic
      intima-medias of the control group, whereas it was clearly induced as early as
      after 3 weeks. 15-LO expression increased further in the 6- and 14-week groups.
      According to in situ hybridization and immunocytochemical studies, 15-LO was
      localized to macrophagerich areas. In Watanabe heritable hyperlipidemic rabbits,
      15-LO mRNA was undetectable in normal aortic intima-medias. 15-LO mRNA was
      markedly induced in fatty streaks but less so in more advanced lesions.
      Identification of the induced LO as reticulocyte-type 15-LO was done by cloning
      and sequencing. We also observed a distinct basal expression of copper-zinc and
      extracellular superoxide dismutases in normal aortic intima-medias, but no clear
      induction of these mRNAs was detected in atherosclerotic aortas. CONCLUSIONS: The
      results show that, in contrast to copper-zinc and extracellular superoxide
      dismutases, the expression of reticulocyte-type 15-LO is markedly induced in
      rabbit fatty streaks. This may lead to an increase in the oxidative potential
      during the early phase of atherogenesis and contribute to the development of
      atherosclerotic lesions.

PMID- 7586320
TI  - Catalase inhibition with 3-amino-1,2,4-triazole does not abolish infarct size
      reduction in heat-shocked rats.
AB  - BACKGROUND: Recent studies have shown that improved myocardial salvage after heat
      shock pretreatment correlates with the amount of induced cardiac heat-shock
      protein (HSP)72. However, heat shock also induces myocardial catalase activity,
      potentially reducing free radical-mediated ischemic injury. The aim of the
      present study was to determine whether catalase inhibition with 3-amino-1,2,4
      triazole (3-AT) abolishes the reduction of infarct size conferred by heat-shock
      treatment in rats. METHODS AND RESULTS: Myocardial catalase activity was measured
      in both heat-shocked and control rats 60 minutes after either 3-AT (1000 mg/kg
      IV) or saline infusion. In separate experiments, heat-shocked and control rats
      were treated with 3-AT or saline 60 minutes before being subjected to 35 minutes
      of left coronary artery occlusion and 120 minutes of reperfusion. Infarct size
      was determined by dual perfusion with triphenyltetrazolium chloride and
      phthalocyanine blue dye. Heat-shock treatment significantly increased myocardial
      catalase compared with control animals (180.5 +/- 4.8, n = 6, versus 86.2 +/-
      14.7, n = 5, units/g wet wt; P < .05). Treatment with 3-AT significantly reduced
      myocardial catalase activity in both heat-shocked and control animals (29.6 +/-
      5.7, n = 5, and 36.4 +/- 15.3, n = 6, respectively). Heat-shock treatment
      significantly reduced infarct size in rats that were both treated and untreated
      with 3-AT compared with respective control groups (22.5 +/- 3.7%, n = 26, 28.2 +/
      4.0%, n = 22, 52.0 +/- 3.0%, n = 23, and 48.6 +/- 3.2%, n = 26, respectively; P
      < .0001 for both heat-shocked groups versus both control groups; infarct
      mass/risk area mass x 100). CONCLUSIONS: Catalase inhibition with 3-AT does not
      abolish the reduction of infarct size in heat-shocked rats.

PMID- 7586319
TI  - Endothelin at pathophysiological concentrations mediates coronary
      vasoconstriction via the endothelin-A receptor.
AB  - BACKGROUND: Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor
      peptide. Controversy persists regarding the predominant ET receptor that mediates
      coronary vasoconstriction at pathophysiological concentrations. The aim of the
      present study was to test the hypothesis that ET mediates local coronary
      vasoconstriction via the ET-A receptor at low concentrations of exogenous ET-1
      designed to mimic pathophysiological states compared with pharmacological
      concentrations. METHODS AND RESULTS: ET-1 (group 1, n = 5) or sarafotoxin, a
      specific ET-B receptor agonist (group 3, n = 6) (each at 2 ng/kg per minute), was
      infused into the left circumflex coronary artery in the anesthetized dog. In
      group 2 dogs (n = 5), the same dose of ET-1 was infused with 4 micrograms/kg per
      minute of the specific ET-A receptor antagonist FR-139317. In group 4 (n = 5),
      the same dose of sarafotoxin was infused with 50 micrograms/kg per minute of the
      specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA).
      No difference in hemodynamics, coronary blood flow (CBF), coronary vascular
      resistance (CVR), or coronary artery diameter (CAD) was observed at baseline
      between the groups. In group 1, intracoronary ET-1 significantly decreased CBF
      and CAD in association with an increase in CVR. The percentage decrease in CBF
      and CAD in the group that received ET-1 and the ET-A receptor antagonist (group
      2) was significantly less than that in the group that received ET-1 alone (group
      1) (-12 +/- 3% versus -48 +/- 6% [P < .001] and -4.6 +/- 0.8 versus 1.0 +/- 0.3
      [P < .05], respectively). The administration of the ET-A receptor antagonist
      (group 2) abolished the ET-mediated increase in CVR (7 +/- 5% versus 105 +/- 21%,
      P < .005). There was no significant effect on CBF, CVR, or CAD in the group
      receiving sarafotoxin alone (group 3). The administration of L-NMMA and
      sarafotoxin (group 3). The administration of L-NMMA and sarafotoxin (group 4)
      resulted in a significant percentage decrease in CBF compared with the group that
      received sarafotoxin alone (-28 +/- 7% versus -8 +/- 2% [P < .05]). CONCLUSIONS:
      The present study demonstrates that low concentrations of exogenous ET-1, which
      may mimic pathophysiological concentrations, result in coronary vasoconstriction
      mediated predominantly via the ET-A receptor because such vasoconstriction is
      significantly attenuated by blockade with FR-139317. The ET-B receptor may have a
      dual vasoconstrictive and vasodilatory effect.

PMID- 7586321
TI  - Tissue factor mediates prolonged procoagulant activity on the luminal surface of
      balloon-injured aortas in rabbits.
AB  - BACKGROUND: Activation of coagulation has been implicated in both acute
      thrombotic occlusion and restenosis after balloon angioplasty. However,
      concomitant administration of antithrombotic agents has thus far failed to
      prevent these complications. Importantly, the factors contributing to
      procoagulant activity of balloon-injured arteries over time have not been
      defined. This study was designed to determine the duration of procoagulant
      activity on the luminal surface of balloon-injured arteries and the relative
      roles of tissue factor and thrombin in this response. METHODS AND RESULTS:
      Abdominal aortas in rabbits were subjected to repetitive balloon hyperinflations
      sufficient to disrupt the internal elastic lamina. Aortas were excised at < 1, 2,
      4, 8, 16, 24, 48, and 72 hours and 1, 2, and 4 weeks after injury; divided into
      segments; and perfused with recalcified human pooled plasma (n = 58) or plasma
      depleted of vitamin K-dependent coagulation factors (n = 27) or first incubated
      with a monoclonal antibody to rabbit tissue factor (n = 33) followed by perfusion
      with human plasma. Samples of the effluent and plasma perfusate were collected
      over 10 minutes and assayed for fibrinopeptide A (FPA) as an index of the rate of
      thrombin-induced fibrin formation. FPA in the effluent from segments perfused
      with recalcified plasma, expressed as a percentage of FPA in the perfusate, was
      elevated for 16 hours after balloon-induced injury and exhibited two distinct
      increases occurring < 1 hour (1297 +/- 473%, mean +/- SD, n = 5) and 8 hours
      (1052 +/- 330%, n = 6) after injury (P < or = .000001 versus uninjured vessels).
      Preincubation of segments at these intervals with an antibody to tissue factor
      markedly attenuated the increases in FPA, as did perfusion of segments with
      plasma depleted of vitamin K-dependent coagulation factors, indicating that the
      observed increases in FPA in whole plasma did not result from performed thrombin
      bound to the injured vessel wall. CONCLUSIONS: Tissue factor-mediated coagulation
      appears to be primarily responsible for prolonged procoagulant activity of
      balloon-injured arteries.

PMID- 7586322
TI  - Effects of pericardial constraint on left ventricular mechanoreceptor activity in
      cats.
AB  - BACKGROUND: The purpose of this study was to assess the effect of pericardial
      constraint on the activity of left ventricular (LV) mechanoreceptors with
      nonmyelinated vagal afferents. METHODS AND RESULTS: Single-unit activity of
      cervical vagal afferents (conduction velocity, 1.6 +/- 0.5 m/s) was recorded in
      six cats anesthetized with alpha-chloralose. Discharge frequency during diastole
      (DFdiastole) and systole (DFsystole) was determined after correction for
      conduction delay of the nerve action potential. When the pericardium was closed
      and LV end-diastolic pressure (LVEDP) was approximately 5 mm Hg, DFdiastole and
      DFsystole were 1.3 +/- 1.0 and 0.3 +/- 0.1 impulses per second, respectively.
      Volume expansion increased LVEDP, LV transmural LVEDP, and segment length and was
      associated with a significant increase in DFdiastole. At a given LVEDP,
      DFdiastole was significantly greater in the absence of the pericardium than with
      the pericardium closed. Removal of the pericardium increased the slope of the
      relation between DFdiastole and intracavitary LVEDP but did not alter the slope
      of the relations between DFdiastole and transmural LVEDP and LV segment length.
      CONCLUSIONS: These results suggest that, rather than the absolute value of
      intracavitary LVEDP, transmural LVEDP and distension appear to be more important
      determinants of diastolic LV mechanoreceptor activity and that pericardial
      constraint may attenuate mechanoreceptor activity by limiting cardiac distension.

PMID- 7586323
TI  - Endothelium-dependent hyperpolarization. Beyond nitric oxide and cyclic GMP.

PMID- 7586324
TI  - Clinical misconceptions dispelled by epidemiological research.
AB  - The epidemiological approach to investigation of cardiovascular disease was
      innovated in 1948 by Ancel Keys' Seven Countries Study and T.R. Dawber's
      Framingham Heart Study. Conducted in representative samples of the general
      population, these investigations provided an undistorted perception of the
      clinical spectrum of cardiovascular disease, its incidence and prognosis, the
      lifestyles and personal attributes that predispose to cardiovascular disease, and
      clues to pathogenesis. The many insights gained corrected numerous widely held
      misconceptions derived from clinical studies. It was learned, for example, that
      the adverse consequences of hypertension do not derive chiefly from the diastolic
      pressure, left ventricular hypertrophy was not an incidental compensatory
      phenomenon, and small amounts of proteinuria were more than orthostatic trivia.
      Exercise was considered dangerous for cardiovascular disease candidates; smoking,
      cholesterol, and a fatty diet were regarded as questionable promoters of
      atherosclerosis. The entities of sudden death and unrecognized myocardial
      infarction were not widely appreciated as prominent features of coronary disease,
      and the disabling and lethal nature of cardiac failure and atrial fibrillation
      was underestimated. It took epidemiological research to coin the term "risk
      factor" and dispel the notion that cardiovascular disease must have a single
      origin. Epidemiological investigation provided health professionals with
      multifactorial risk profiles to more efficiently target candidates for
      cardiovascular disease for preventive measures. Clinicians now look to
      epidemiological research to provide definitive information about possible
      predisposing factors for cardiovascular disease and preventive measures that are
      justified. As a result, clinicians are less inclined to regard usual or average
      values as acceptable and are more inclined to regard optimal values as "normal."
      Cardiovascular events are coming to be regarded as a medical failure rather than
      the first indication of treatment.

PMID- 7586318
TI  - Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P
      selectin surface expression in human umbilical vein endothelial cells.
AB  - BACKGROUND: The peptido-leukotrienes (LTs) and lipoxins (LX) are produced by
      platelets through the transcellular conversion of leukocyte-derived LTA4 at sites
      of vascular inflammation and injury, such as during coronary artery balloon
      angioplasty. We studied the actions of these eicosanoids on vascular endothelium.
      METHODS AND RESULTS: We found that stimulation of cultured human umbilical vein
      endothelial cells (EC) with LTC4 and LTD4 resulted in the release of high
      molecular-weight multimers of von Willebrand factor (vWF) in a concentration- and
      time-dependent fashion, as measured by ELISA. Neither LXA4 nor LXB4 stimulated
      vWF release. LTC4 and LTD4 also stimulated a rapid increase in the surface
      expression of P-selectin indicated by increased binding of anti-P-selectin
      monoclonal antibody-coated beads. Fluorescence cytometry detected prolonged peaks
      of [Ca2+]i in EC in response to concentrations of thrombin and LTD4 that induce
      near-maximal vWF secretion. In contrast, concentrations of LTC4 that induce
      similar levels of vWF secretion produced only asynchronous oscillations of
      [Ca2+]i in most EC and rarely induced prolonged peaks of [Ca2+]i. Depletion of
      external Ca2+ had no apparent impact on LT-stimulated [Ca2+]i transients and vWF
      secretion, implicating an intracellular pool as the source of this response.
      Staurosporine, sphingosine, and H-7 each had only modest effects on peptido-LT
      induced vWF secretion, suggesting that protein kinase C is not a primary mediator
      of peptido-LT-induced exocytosis. Inhibitors of cyclooxygenase and platelet
      activating factor had no effect on peptido-LT-mediated vWF secretion.
      CONCLUSIONS: Through the induction of vWF secretion and P-selectin surface
      expression, peptido-LTs are likely to play an important role in the interrelated
      processes of hemostasis and inflammation.

PMID- 7586325
TI  - Depression after myocardial infarction.

PMID- 7586326
TI  - Dependence of soluble tumor necrosis factor receptor 1 and 2 values on the
      severity and duration of ischemic heart disease.

PMID- 7586329
TI  - Images in cardiovascular medicine. Kawasaki's disease.

PMID- 7586327
TI  - Quantitating serial intracoronary ultrasound.

PMID- 7586328
TI  - Departure from Hardy-Weinberg equilibrium should be systematically tested in
      studies of association between genetic markers and disease.

PMID- 7586330
TI  - The 1995 European Society of Cardiology.

PMID- 7586331
TI  - Low serum cholesterol. Hazardous to health?

PMID- 7586332
TI  - Magnesium in acute MI. Timing is critical.

PMID- 7586333
TI  - Blockade of platelet GPIIb/IIIa receptors as an antithrombotic strategy.

PMID- 7586336
TI  - Transient myocardial contrast after initial exposure to diagnostic ultrasound
      pressures with minute doses of intravenously injected microbubbles. Demonstration
      and potential mechanisms.
AB  - BACKGROUND: We have observed a transient but significant increase in myocardial
      contrast intensity with intravenously injected perfluorocarbon-exposed sonicated
      dextrose albumin (PESDA) microbubbles that occurs on initial exposure to pulsed
      ultrasound (transient-response imaging). The characteristics and magnitude of
      this response were examined in the present study. METHODS AND RESULTS: In 14
      dogs, the myocardial contrast intensity produced by transient-response imaging
      (TRI) was compared with conventional 30-Hz imaging (CI) after a 0.005 to 0.030
      mL/kg intravenous injection of PESDA. TRI was produced either by measuring
      myocardial contrast during triggered (1 pulse per cardiac cycle) ultrasound or by
      withholding real time ultrasound transmission until after microbubbles had
      entered the myocardium after intravenous injection. Both first-harmonic imaging
      (2.0 to 3.5 MHz) and second-harmonic imaging (2.0 to 2.5 MHz fundamental, 4.0 to
      5.0 MHz received) were used. TRI produced over three times the anterior
      myocardial contrast intensity of CI (36 +/- 12 U TRI versus 11 +/- 11 U CI; P <
      .01), with visually better anterior and posterior myocardial contrast. The
      spatial extent of myocardial ischemia was easily visualized after intravenous
      PESDA by use of TRI and correlated closely with risk area as measured with
      Monastral blue (r = .99, P = .002). CONCLUSIONS: TRI produces significantly
      greater myocardial contrast than CI and may dramatically enhance the ability of
      intravenous ultrasound contrast agents to identify myocardial perfusion
      abnormalities.

PMID- 7586334
TI  - Genetic linkage of the ACE gene to plasma angiotensin-converting enzyme activity
      but not to blood pressure. A quantitative trait locus confers identical complex
      phenotypes in human and rat hypertension.
AB  - BACKGROUND: An allelic variant of the ACE gene has been found to be linked to
      plasma angiotensin-converting enzyme (ACE) activity in humans and has been
      implicated in the etiology of some common cardiovascular disorders. Previously,
      we have shown significant genetic linkage of blood pressure to a region on rat
      chromosome 10 that contains ACE in an experimental F2-intercross between the
      stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar
      Kyoto (WKYHD-0) reference strain. Subsequent investigations revealed marked
      differences in plasma ACE activity among the SHRSPHD and WKYHD-0 strains.
      Nonetheless, the physiological relevance of these findings remained obscure. We
      therefore investigated the genetic determination of plasma ACE activity and its
      relation to blood pressure and dietary NaCl exposure in a model of experimental
      genetic hypertension, the SHRSPHD. METHODS AND RESULTS: We conducted a further
      crossbreeding experiment between SHRSPHD and a congenic reference strain, WKYHD
      1, that carries a 6-centimorgan (cM) long, SHRSP-homologous segment introgressed
      in chromosome 10, 26 cM remote from ACE. This allowed us to contrast effects on
      blood pressure and ACE activity conferred by the ACE locus with other more remote
      loci within the congenic chromosomal region. Genetic analysis in this F2 (WKYHD-1
      x SHRSPHD) cross revealed that plasma ACE activity was determined almost entirely
      by genetic effects of the ACE gene locus (lod score = 43). However, neither
      plasma ACE nor the ACE locus showed any cosegregation with blood pressure before
      or after dietary NaCl exposure. CONCLUSIONS: These results demonstrate that a
      molecular variant of the ACE gene determines plasma ACE activity but exhibits no
      direct effect on blood pressure. Moreover, the findings also exclude the
      possibility that plasma ACE is secondarily affected by blood pressure or excess
      dietary NaCl exposure. Our results reconcile the previous discrepancy between
      findings in human and experimental hypertension.

PMID- 7586335
TI  - Pressure- and volume-induced left ventricular hypertrophies are associated with
      distinct myocyte phenotypes and differential induction of peptide growth factor
      mRNAs.
AB  - BACKGROUND: Chronic pressure and volume overload (PO and VO) result in
      morphologically and functionally distinct forms of myocardial hypertrophy. We
      tested the hypothesis that PO- and VO-induced left ventricular (LV) hypertrophies
      are associated with distinct molecular phenotypes and patterns of peptide growth
      factor induction. METHODS AND RESULTS: mRNA levels were quantified in LV
      myocardium from rats with LV hypertrophy due to PO or VO caused by suprarenal
      aortic constriction or an abdominal aortocaval fistula, respectively, for 1 week.
      Although PO and VO caused comparable increases in LV weight and preproatrial
      natriuretic factor mRNA, PO but not VO increased mRNA levels for the fetal genes
      beta-myosin heavy chain and skeletal alpha-actin and reduced the mRNA level of
      sarcoplasmic reticulum Ca2+ATPase. In a myocyte-enriched myocardial fraction,
      transforming growth factor-beta 3 and insulin-like growth factor-1 mRNA levels
      were increased with PO but not VO; acidic fibroblast growth factor mRNA was
      unchanged with PO but decreased with VO. In a nonmyocyte-enriched myocardial
      fraction, transforming growth factor-beta 3 and insulin-like growth factor-1 mRNA
      levels were decreased with VO but unchanged with PO. CONCLUSIONS: PO- and VO
      induced LV hypertrophies are associated with distinct molecular phenotypes and
      patterns of peptide growth factor induction. Stimulus-specific heterogeneity in
      the signaling events and peptide growth factors coupled to gene expression could
      play a role in determining the type of hypertrophy that is caused by various
      forms of hemodynamic overload.

PMID- 7586337
TI  - Low serum cholesterol and mortality. Which is the cause and which is the effect?
AB  - BACKGROUND: Many studies have reported an association between a low or lowered
      blood total cholesterol (TC) level and subsequent nonatherosclerotic disease
      incidence or death. The question of whether low TC is a true risk factor or
      alternatively a consequence of occult disease at the time of TC measurement
      remains unsettled. To shed new light onto this problem, we analyzed TC change
      over a 6- year period (from exam 1 in 1965 through 1968 to exam 3 in 1971 through
      1974) in relation to subsequent 16-year mortality in a cohort of Japanese
      American men. METHODS AND RESULTS: The study was based on 5941 men 45 to 68 years
      of age without prior history of coronary heart disease, stroke, cancer, or
      gastrointestinal-liver disease at exam 1 who also participated in exam 3 of the
      Honolulu Heart Program. The association of TC change with mortality end points
      was investigated with two different approaches (continuous and categorical TC
      change) with standard survival analysis techniques. Falling TC level was
      accompanied by a subsequent increased risk of death caused by some cancers
      (hemopoietic, esophageal, and prostate), noncardiovascular noncancer causes
      (particularly liver disease), and all causes. The risk-factor-adjusted rate of
      all-cause mortality was 30% higher (relative risk, 1.30; 95% CI, 1.06 to 1.59)
      among persons with a decline from middle (180 to 239 mg/dL) to low (< 180 mg/dL)
      TC than in persons remaining at a stable middle level. By contrast, there was no
      significant increase in all-cause mortality risk among cohort men with stable low
      TC levels. Nonillness mortality (deaths caused by trauma and suicide) was not
      related to either TC change or the average of TC levels in exams 1 and 3.
      CONCLUSIONS: These results add strength to the reverse-causality proposition that
      catabolic diseases cause TC to decrease.

PMID- 7586338
TI  - Effects of cholesterol lowering on the progression of coronary atherosclerosis in
      women. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) substudy.
AB  - BACKGROUND: Although coronary disease is the leading cause of death in women and
      its clinical features differ from those in men, very few women have been included
      in angiographic trials of cholesterol lowering. METHODS AND RESULTS: Sixty-two
      women with diffuse but not necessarily severe coronary atherosclerosis documented
      on a recent angiogram and with fasting serum cholesterol between 220 and 300
      mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one
      half had a history of hypertension, approximately one quarter were diabetics, and
      one third were current smokers. All women received dietary counseling. Lovastatin
      or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to
      80 mg during the first 16 weeks to attain a fasting LDL cholesterol < or = 130
      mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased
      by 24% and 32%, respectively, in lovastatin-treated women but by < 3% in women
      receiving placebo. Coronary arteriography was repeated after 2 years in 54 women
      (87%), and their 394 lesions were measured "blindly" on pairs of film with an
      automated computerized quantitative system. Progression, defined as a worsening
      in minimum diameter of one or more stenoses by > or = 0.4 mm, occurred in 7 of 25
      lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%, P =
      .031). New coronary lesions developed in 1 lovastatin-treated woman and 13
      placebo-treated women (4% versus 45%, P < .001). The outcome for each of the
      angiographic end points was not significantly different between the women and the
      245 men who completed the trial. CONCLUSIONS: Lovastatin slows the progression of
      coronary atherosclerosis and prevents the development of new coronary lesions in
      women.

PMID- 7586342
TI  - Cigarette smoking acutely increases platelet thrombus formation in patients with
      coronary artery disease taking aspirin.
AB  - BACKGROUND: Smoking is associated with an increased risk of myocardial infarction
      and sudden death. Platelet activation and thrombosis at sites of vessel stenosis
      and injury or plaque disruption play a crucial role in these acute coronary
      events. Thus, the aim of this study was to determine whether cigarette smoking
      acutely increases platelet thrombus formation on an injured arterial surface at
      local shear rates typical of a stenotic artery. METHODS AND RESULTS: Twelve
      habitual smokers with stable coronary disease, on aspirin 325 mg/d, were studied
      immediately before and 5 minutes after smoking two cigarettes each. Ex vivo
      platelet thrombus formation on porcine arterial media (simulating deep arterial
      injury) was measured after exposure to the patient's circulating venous blood for
      3 minutes in cylindrical flow chambers at 37 degrees C. The flow chambers were
      designed to produce shear rates of 754 or 2546 s-1, the latter being typical of
      the high shear rates produced by vessel stenosis. Plasma catecholamine,
      thromboxane B2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels and
      whole blood platelet aggregation responses to thrombin were also measured before
      and after smoking. Compared with before smoking, morphometrically measured
      platelet thrombus formation on arterial media at shear rates of 754 and 2546 s-1
      increased by an average of 48% (P = .19) and 64% (P = .014), respectively, after
      smoking. Plasma epinephrine increased by more than twofold after smoking (P =
      .026). Plasma thromboxane B2 and 6-keto-PGF1 alpha levels did not change. Smoking
      also increased whole blood platelet aggregation to thrombin (P < or = .05).
      CONCLUSIONS: These results suggest that smoking-enhanced platelet thrombosis may
      be an important contributory mechanism for acute coronary events in smokers that
      is not prevented by aspirin treatment. Catecholamine release and heightened
      platelet aggregation response to in vivo agonists may contribute to the
      prothrombotic effects of smoking.

PMID- 7586340
TI  - Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of
      clinical events of the Pravastatin Atherosclerosis Intervention Program.
AB  - BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors,
      or statins, can decrease cardiovascular events and mortality in patients with
      clinical coronary disease and moderately to severely elevated lipid levels.
      Additional data are required to demonstrate a reduction of vascular events in
      coronary patients with less than severely elevated lipid levels and in subgroups
      of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis
      regression trials that evaluated pravastatin were pooled for a predetermined
      analysis of the effect of that agent on the risk of coronary events. All trials
      were double-masked, placebo-controlled designs that used pravastatin as
      monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of
      atherosclerosis and mildly to moderately elevated lipid levels. For fatal or
      nonfatal myocardial infarction, there was a 62% reduction in events attributable
      to pravastatin (P = .001). This effect was evident in younger and older patients,
      men and women, and patients with and without histories of hypertension and prior
      infarction. There was a 46% reduction in all-cause mortality (P = .17), which,
      although not statistically significant, is consistent with the results of other
      statin trials. There also was a 62% reduction in the risk of fatal or nonfatal
      stroke (P = .054). CONCLUSIONS: These pooled results provide strong evidence that
      pravastatin reduces the risk of cardiovascular events in patients with
      atherosclerotic disease and mildly to moderately elevated lipid levels. The
      benefit for reducing myocardial infarction is evident in older and younger
      patients, men and women, and patients with and without histories of hypertension
      and prior infarction.

PMID- 7586341
TI  - Endothelin in coronary endothelial dysfunction and early atherosclerosis in
      humans.
AB  - BACKGROUND: The endothelium modulates vascular tone through release of
      vasodilating substances, such as endothelium-derived relaxing factors, and
      vasoconstricting substances, such as endothelin. Endothelin concentrations are
      elevated in humans with atherosclerosis and in hypercholesterolemic pigs.
      Furthermore, the endothelium-dependent vasodilator acetylcholine increases
      endothelin in hypercholesterolemia in association with coronary vasoconstriction.
      The present study was designed to test the hypotheses that coronary endothelial
      dysfunction in humans is characterized by enhanced coronary and circulating
      endothelin and that the vasoconstriction associated with acetylcholine results in
      further release of coronary endothelin. METHODS AND RESULTS: Coronary and
      circulating endothelin concentrations were measured at baseline and during
      intracoronary acetylcholine administration in 20 patients undergoing diagnostic
      coronary angiography. Patients were divided into two groups on the basis of their
      response to intracoronary acetylcholine. Group 1 (n = 7) demonstrated a normal
      vasodilatory response, but group 2 (n = 13) demonstrated coronary
      vasoconstriction. Baseline coronary and circulating endothelin concentrations (as
      determined by coronary sinus and femoral artery measurements, respectively) were
      higher in patients who responded to acetylcholine with coronary vasoconstriction
      (group 2) than in group 1 patients (coronary sinus, 15.9 +/- 1.0 pg/mL versus 7.1
      +/- 1.0 pg/mL; femoral, 14.1 +/- 0.9 pg/mL versus 6.8 +/- 1.0 pg/mL,
      respectively; P < .01). In response to intracoronary acetylcholine, a further
      increase in coronary endothelin was observed only in group 2; this increase
      correlated with changes in coronary artery diameter. CONCLUSIONS: This study
      demonstrates that endothelin immunoreactivity is enhanced in the coronary and
      systemic circulation in humans with coronary endothelial dysfunction. Moreover,
      acetylcholine further increased coronary endothelin concentration in patients
      with coronary endothelial dysfunction and was associated with coronary
      vasoconstriction. These observations strongly support a role for endothelin as an
      early participant in and marker for coronary endothelial dysfunction in humans.

PMID- 7586339
TI  - Compensatory vascular changes of remote coronary segments in response to lesion
      progression as observed by sequential angiography from a controlled clinical
      trial.
AB  - BACKGROUND: Local coronary artery enlargement to compensate for atherosclerotic
      plaques preserves the vessel lumen. The extent to which coronary segments remote
      from progressing lesions enlarge is unknown. This is clinically relevant since
      compensatory enlargement may be important in determining whether clinical
      complications result from progression of coronary artery disease (CAD).
      Additionally, compensatory change has implications for quantitative coronary
      angiographic (QCA) trials, since the effect of progression on diameter means may
      be mitigated by compensatory changes in remote coronary segments when QCA change
      is averaged over all lesions. METHODS AND RESULTS: Serial QCA data from 78
      subjects in the Monitored Atherosclerosis Regression Study were used to
      demonstrate compensatory changes in coronary segments remote from progressing or
      regressing lesions. Coronary segments were first classified as progressing
      (regressing) if percent diameter stenosis (PS) increased or decreased by > 10
      with a concurrent decrease or increase in minimum lumen diameter (MLD) of either
      > 0.32 mm or > 10% of the normal baseline reference diameter (DNORM). Segments
      not meeting these criteria were labeled stenosis stable. Stenosis-stable segments
      opposite progressing lesions showed increases in MLD (P = .0006), DNORM (P =
      .001), and average diameter (P = .001). On-trial apolipoprotein (apo) B, apo C
      III, and blood pressure levels inversely correlated with these compensatory
      changes. CONCLUSIONS: Lesion progression in one coronary segment is associated
      with significant increases in segmental diameter of remote parts of the coronary
      tree. We hypothesize these increases to be vascular compensatory changes in
      response to progression of CAD. Vascular compensatory change is enhanced by LDL
      cholesterol and triglyceride-rich lipoprotein reduction and appears to be part of
      the treatment effect itself.

PMID- 7586345
TI  - Coronary arterial flow-velocity dynamics in children with angiographically normal
      coronary arteries.
AB  - BACKGROUND: There have been few reports about coronary hemodynamics in children
      during the process of growth. In the present study, to assess the characteristics
      of coronary flow dynamics in children, we examined the phasic coronary flow
      velocity (CFV) patterns at rest and during peak hyperemic responses in children
      with angiographically normal coronary arteries. METHODS AND RESULTS: Spectral
      Doppler phasic coronary flow velocity was recorded with a 0.018-in intracoronary
      Doppler guidewire at rest and during peak responses after intracoronary bolus
      injection of ATP in 30 patients with Kawasaki's disease (age, 8.2 +/- 5.1 years;
      24 boys and 6 girls) without angiographic coronary lesions. Average peak velocity
      (APV), maximum peak velocity (MPV), and diastolic-to-systolic velocity ratio
      (DSVR) were evaluated in the left anterior descending coronary artery (LAD), left
      circumflex artery (LCx), and right coronary artery (RCA). Coronary vasodilator
      reserve (coronary flow reserve [CFR]) was calculated as the ratio of ATP-induced
      hyperemic to baseline APV. Flow-velocity parameters in RCA were significantly
      lower than those in the LAD and LCx in both proximal and distal portions.
      Although the distal LCx had significantly lower values of APV and MPV than did
      the proximal LCx, there was no significant difference between the proximal and
      distal portions of the LAD and RCA for APV and MPV. All three coronary vessels
      showed a diastolic dominant flow pattern in each segment. This coronary flow
      pattern was less marked in the RCA than in the LCA. All three coronary vessels
      showed a significant increase in APV and a significantly decrease in DSVR after
      ATP administration. CFR was significantly lower in the LCx than in the LAD or RCA
      (P < .01: 1.93 +/- 0.34 in LCx versus 2.32 +/- 0.42 in LAD and 2.37 +/- 0.44 in
      RCA). From the view of aging, it was revealed that APV values in three vessels
      were higher in the younger group than in the older group. CFR values in the LAD
      and LCx were significantly lower in the younger group than in the older group (P
      < .001 in LAD: 2.01 +/- 0.28 in the younger versus 2.53 +/- 0.37 in the older; P
      < .01 in LCx: 1.61 +/- 0.15 in the younger versus 2.06 +/- 0.31 in the older). In
      addition, intracoronary injection of ATP did not increase the absolute
      angiographic coronary luminal diameter. CONCLUSIONS: With the use of an
      intracoronary Doppler guidewire, we demonstrated that there are some
      characteristic findings in CFV dynamics in childhood. These physiological
      characteristics in CFV dynamics that occur with aging and occur in each vessel
      must be taken into consideration in the study of the coronary circulation in
      children.

PMID- 7586344
TI  - Progression and regression of coronary stenosis in the long-term follow-up of
      vasospastic angina.
AB  - BACKGROUND: Whether focal vasospasticity plays a pathogenic role in the
      progression or regression of coronary atherosclerosis is unknown. To determine
      whether evidence for such a role exists, we studied long-term changes in coronary
      luminal measurements in patients with vasospastic angina. METHODS AND RESULTS:
      Quantitative coronary angiography and repeated ergonovine provocation tests were
      performed 45 +/- 16 months apart in 30 patients. All patients had vasospastic
      anginal symptoms and coronary spasm on the initial provocation test. On the 30
      patients, 16 had persistent symptoms of vasospastic angina and showed coronary
      spasm at the same site on the follow-up angiogram (group 1), while the remaining
      14 whose vasospastic anginal symptoms disappeared at follow-up demonstrated a
      negative response to ergonovine on the follow-up tests (group 2). There was no
      significant difference in patients' baseline characteristics between the two
      groups. Long-term changes in minimal (MLD) and mean (MEAN) luminal diameter were
      measured (in millimeters) after administration of isosorbide dinitrate in 19
      spastic and 93 nonspastic segments in group 1 and in 17 previously spastic and 81
      nonspastic segments in group 2. Both MLD and MEAN were measured in 210 coronary
      segments of the 30 patients at baseline and after administration of ergonovine
      and isosorbide dinitrate by use of a computer-based quantitative coronary
      angiography system. Stenosis progression and regression of individual lesions
      were defined as a change in MLD of > or = 0.40 mm. In group 1, both the MLD and
      MEAN of 19 spastic segments were significantly smaller (progression) at follow-up
      compared with the initial angiogram (MLD, 2.21 +/- 0.54 initially versus 1.95 +/-
      0.65 at follow-up, P < .01; MEAN, 2.80 +/- 0.56 initially versus 2.56 +/- 0.58 at
      follow-up, P < .01), whereas the MLD and MEAN of 93 nonspastic segments in group
      1 were not significantly different between the initial and follow-up angiograms
      (MLD, 2.47 +/- 0.67 initially versus 2.44 +/- 0.69 at follow-up, P = NS; MEAN,
      2.96 +/- 0.69 initially versus 2.91 +/- 0.68 at follow-up, P = NS). In group 2,
      the MLD of the 17 previously spastic segments significantly improved (regression)
      at follow-up (MLD, 1.99 +/- 0.68 initially versus 2.24 +/- 0.54 at follow-up, P <
      .05); the MLD and MEAN of the 81 nonspastic segments were not significantly
      different (MLD, 2.36 +/- 0.59 initially versus 2.39 +/- 0.60 at follow-up, P =
      NS; MEAN, 2.81 +/- 0.58 initially versus 2.81 +/- 0.61 at follow-up, P = NS). In
      group 1, significant stenosis progression of individual lesions was observed more
      frequently at spastic than nonspastic segments (6 of 19 versus 10 of 93, P <
      .05), whereas stenosis regression was observed in no spastic and 3 nonspastic
      segments (P = NS). In group 2, stenosis progression was observed at 1 previously
      spastic segment and 4 nonspastic segments (P = NS), while significant stenosis
      regression of individual lesions was seen more commonly in previously spastic
      than nonspastic segments (6 of 17 versus 7 of 81, P < .01). CONCLUSIONS: These
      results have demonstrated in patients an association between persistent
      vasospastic activity and progression of atherosclerosis and an association
      between cessation of vasospastic activity and regression of atherosclerosis.

PMID- 7586343
TI  - Blood pressure and mortality among men with prior myocardial infarction. Multiple
      Risk Factor Intervention Trial Research Group.
AB  - BACKGROUND: The purpose of the present study was to describe the relation between
      blood pressure (systolic [SBP] and diastolic [DBP]) and death from coronary heart
      disease (CHD) and all causes for men with a history of myocardial infarction
      (MI). METHODS AND RESULTS: The study cohort consisted of men aged 35 to 57 years
      screened for the Multiple Risk Factor Intervention Trial (MRFIT) in 1973 through
      1975 and followed for survival for an average of 16 years through 1990. There
      were 5362 men who reported prior hospitalization for a heart attack of at least 2
      weeks' duration at the initial screening of MRFIT. There was a J-shaped relation
      between SBP and DBP with both CHD and all-cause mortality during the first 2
      years of follow-up in older (age, 45 to 57 years) men only. Risk nadirs for SBP
      were 152 and 145 mm Hg, respectively, for CHD death and all-cause mortality;
      corresponding DBP risk nadirs were 94 and 90 mm Hg. After the first 2 years,
      there was a positive association between SBP and death from CHD and all causes.
      By 15 years, cumulative CHD mortality percentages for men with screening SBP <
      120, 120 to 139, 140 to 159, and > or = 160 mm Hg were 19.7%, 21.3%, 27.5%, and
      32.0%, respectively. When deaths only after year 2 were considered, although the
      linear DBP coefficient was significant, the quadratic term for DBP was no longer
      significant (P > .05). However, the relation still appeared J-shaped as
      cumulative mortality for those with DBP < 70, 70 to 79, 80 to 89, 90 to 99, and >
      or = 100 mm Hg was 24.3%, 20.8%, 21.1%, 25.5%, and 29.7%, respectively. When the
      joint relation of SBP and DBP was considered, there were no survival differences
      among the four cohorts (SBP > or = 140 and DBP < 80, SBP > or = 140 and DBP > or
      = 80, SBP < or = 140 and DBP < 80, and SBP < or = 140 and DBP > or = 80) during
      the first 2 years. After 2 years, both CHD and all-cause mortality rates were
      approximately 40% higher for participants with SBP > or = 140 mm Hg versus < 140
      mm Hg regardless of DBP level (< 80 or > or = 80 mm Hg). CONCLUSIONS: In this
      large cohort of men with prior MI, the association of SBP and DBP with CHD and
      all-cause mortality varied over the 16-year follow-up period. During early follow
      up, in older men only, J- or U-shaped relations were evident. However, after 2
      years, these same relations had become positive and graded. Given the substantial
      excess mortality risk in this cohort associated with high blood pressure,
      particularly SBP, efforts to gradually lower blood pressure should receive high
      priority among hypertensive men with prior MI.

PMID- 7586347
TI  - Relation of coronary angioscopic findings at coronary angioplasty to angiographic
      restenosis.
AB  - BACKGROUND: Discordant results have been reported regarding morphological
      predictors of restenosis after percutaneous transluminal coronary angioplasty
      (PTCA). These discrepancies may be related to the limitations of angiography in
      the study of plaque morphology. METHODS AND RESULTS: We studied 117 consecutive
      patients who underwent successful PTCA and who underwent coronary angioscopy
      before and immediately after the procedure. Angiographic follow-up was performed
      in 99 (85%) patients. We analyzed the relationship between angioscopic variables
      at the time of PTCA and the occurrence of restenosis assessed by quantitative
      coronary angiography. Plaque shape and color had no effect on late loss in
      luminal diameter (late loss: smooth lesions, 0.55 +/- 0.68 mm; complex lesions,
      0.76 +/- 0.60 mm; white plaques, 0.51 +/- 0.56 mm; yellow plaques, 0.65 +/- 0.72
      mm; P = NS). An angioscopic protruding thrombus at the PTCA site was associated
      with significantly greater loss in luminal diameter (late loss: no thrombus, 0.47
      +/- 0.54 mm; lining thrombus, 0.59 +/- 0.67 mm; protruding thrombus, 1.07 +/-
      0.77 mm; P < .05). Dissection assessed by angioscopy immediately after PTCA had
      no effect on late loss in luminal diameter (late loss: no dissection, 0.60 +/-
      0.60 mm; simple dissection, 0.82 +/- 0.75 mm; complex dissection, 0.57 +/- 0.80
      mm; P = NS). CONCLUSIONS: These results show that coronary angioscopy may be
      helpful in predicting the risk of restenosis after PTCA. The high rate of
      angiographic recurrence observed when PTCA is performed at thrombus-containing
      lesions supports a role for thrombus in the process of luminal renarrowing after
      PTCA.

PMID- 7586346
TI  - Intracoronary heparin delivery in humans. Acute feasibility and long-term
      results.
AB  - BACKGROUND: Inefficacy of systemic drug administration for restenosis prevention
      may partially relate to insufficient local drug concentration. This study aimed
      to evaluate the acute feasibility and long-term outcome of using an infusion
      perfusion coil balloon, Dispatch. METHODS AND RESULTS: In 22 patients after
      balloon angioplasty, the coil balloon was studied for (1) feasibility of local
      heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment
      compared with angioplasty balloon occlusion, (3) coronary pressure and flow
      distal to the inflated device, and (4) long-term clinical and angiographic
      results. During prolonged intracoronary deployment of the coil balloon (29 +/- 8
      minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during
      angioplasty (275 +/- 283 seconds). Neither hemodynamic nor vectorcardiographic
      signs of ischemia were detected, in contrast to angioplasty balloon occlusion.
      Baseline flow across the coil balloon was 44 +/- 31 mL/min, increasing by a
      factor of 1.8 +/- 0.7 during pharmacologically induced hyperemia. A mean volume
      of 14.2 +/- 6.1 mL containing 1416 +/- 608 IU of heparin was infused locally at a
      pressure of 122 +/- 54 mm Hg. At 7 +/- 1-month follow-up, 1 asymptomatic patient
      had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic
      follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic
      patients. Mean minimal luminal diameter after the procedure was 2.16 +/- 0.49 mm
      and at follow-up, 1.89 +/- 0.45 mm, which corresponds to a restenosis rate
      (diameter stenosis > or = 50%) of 7% (1/15). CONCLUSIONS: Intracoronary use of
      the coil balloon after balloon angioplasty proved to be feasible and subjectively
      as well as objectively well tolerated during prolonged deployment by virtue of
      its perfusion properties. High volumes of heparin solution can be infused locally
      at very low pressure. No unfavorable clinical or angiographic long-term effects
      were observed.

PMID- 7586348
TI  - In-hospital and one-year economic outcomes after coronary stenting or balloon
      angioplasty. Results from a randomized clinical trial. Stent Restenosis Study
      Investigators.
AB  - BACKGROUND: Coronary stenting has been shown to improve initial success, reduce
      angiographic restenosis, and reduce the need for repeat revascularization
      compared with conventional balloon angioplasty (PTCA). Although previous studies
      have demonstrated that initial hospital costs for stenting are considerably
      higher than those for conventional PTCA, the impact of coronary stenting on long
      term medical care costs remains unknown. METHODS AND RESULTS: Between January
      1991 and June 1993, 207 consecutive patients with symptomatic coronary disease
      requiring revascularization of a single coronary lesion were randomized to
      receive initial treatment by either PTCA (n = 105) or Palmaz-Schatz coronary
      stent implantation (n = 102) in the multicenter STRESS trial. Detailed resource
      utilization and cost data were collected for each patient's initial
      hospitalization and for any subsequent hospital visits for 1 year after
      randomization. Compared with conventional angioplasty, coronary stenting resulted
      in additional catheterization laboratory costs, increased vascular complications,
      and longer length of stay. Initial hospital costs were thus approximately $2200
      higher for stenting than for PTCA ($9738 +/- 3248 versus $7505 +/- 5015; P <
      .001). Over the first year of follow-up, however, patients assigned to initial
      stenting were less likely to require rehospitalization for a cardiac condition
      and underwent fewer subsequent revascularization procedures. Follow-up medical
      care costs thus tended to be lower for stenting than for conventional angioplasty
      ($1918 +/- 4841 versus $3359 +/- 7100, P = .21). Nonetheless, cumulative 1-year
      medical care costs remained higher for patients undergoing initial stenting
      ($11,656 +/- 5674 versus $10,865 +/- 9073, P < .001). Even after adjustment for
      the higher incidence of vascular complications in the stent group, total 1-year
      costs were $300 higher for stenting than for balloon angioplasty. CONCLUSIONS:
      Elective coronary stenting, as performed in the randomized STRESS trial,
      increased total 1-year medical care costs by approximately $800 per patient
      compared with conventional angioplasty. Future studies will be necessary to
      determine whether ongoing refinements in stent design, implantation techniques,
      and anticoagulation regimens can narrow this cost difference further by reducing
      stent-related vascular complications or length of stay.

PMID- 7586349
TI  - Natural history of hypertrophic cardiomyopathy. A population-based study, 1976
      through 1990.
AB  - BACKGROUND: Hypertrophic cardiomyopathy is a disease entity characterized by
      marked heterogeneity in morphology and natural history. Most of our knowledge of
      the natural history of this disorder derives from the study of hospital-based
      populations and is influenced by referral bias. Therefore, this population-based
      study was undertaken to examine the natural history of hypertrophic
      cardiomyopathy among unselected residents of Olmsted County, Minnesota. METHODS
      AND RESULTS: Patients with hypertrophic cardiomyopathy, confirmed by
      echocardiography, were identified by use of the resources of the Rochester
      Epidemiology Project. Patients with the echocardiographic features of
      hypertrophic cardiomyopathy but with long-standing hypertension requiring drug
      therapy were categorized as having hypertensive hypertrophic cardiomyopathy.
      Baseline clinical details and follow-up events were obtained by retrospective
      chart review. Thirty-seven patients were diagnosed with hypertrophic
      cardiomyopathy and 24 with hypertensive hypertrophic cardiomyopathy. Eight
      additional patients were first diagnosed at autopsy. The mean age of the 37
      patients with hypertrophic cardiomyopathy was 59 +/- 20 years (range, 1 week to
      92 years); the mean ventricular septal thickness was 17.5 +/- 3 mm. Follow-up was
      obtained for a median of 7.7 years (range, 45 days to 17.2 years). The 1- and 5
      year survival rates were 95% and 92%, respectively; these rates did not differ
      from those of an age- and sex-matched population (P = NS). The annual risk of
      cardiac death was 0.7%. The mean age of patients with hypertensive hypertrophic
      cardiomyopathy was 79 +/- 8 years (range, 62 to 91 years), and the mean
      ventricular septal thickness was 19 +/- 2.5 mm. Follow-up was obtained for a
      median of 2.8 years (range, 4 days to 16.7 years). The 1- and 5-year survival
      rates were 75% and 43%, respectively, which differed sharply from the expected
      rates of 94% and 70% (P = .0028). The annual risk of cardiac death was 5%. Atrial
      fibrillation and evidence for myocardial infarction on ECG, use of digoxin and
      diuretics, and a high New York Heart Association functional class at presentation
      were all associated with decreased survival by multivariate analysis for both
      groups combined. A history of myocardial infarction, atrial fibrillation, and
      mitral annual calcification at presentation were associated with cardiac death.
      CONCLUSIONS: Hypertrophic cardiomyopathy is a more benign disease than previously
      reported from tertiary referral centers. Patients assessed as having hypertensive
      hypertrophic cardiomyopathy represent a subset at higher risk for cardiac and
      noncardiac death, with an overall decreased survival rate.

PMID- 7586350
TI  - Congestive heart failure after surgical correction of mitral regurgitation. A
      long-term study.
AB  - BACKGROUND: In patients with mitral regurgitation, surgical intervention produces
      immediate improvement in symptoms, but the long-term incidence and significance
      of postoperative congestive heart failure are unknown. METHODS AND RESULTS: The
      long-term outcome of 576 operative survivors of surgical correction of pure
      mitral regurgitation performed between 1980 and 1989 was analyzed. Survival was
      77 +/- 2% and 56 +/- 3% at 5 and 10 years, respectively. Cumulative incidence of
      congestive heart failure was 23 +/- 2%, 33 +/- 3%, and 37 +/- 3% at 5, 10, and 14
      years, respectively. Survival after the first episode of congestive heart failure
      was dismal, 44 +/- 4% at 5 years. Cause of congestive heart failure was left
      ventricular dysfunction in two thirds of the patients and valvular dysfunction in
      the other third. With multivariate analysis, the independent predictors of
      postoperative heart failure were preoperative ejection fraction (P = .0001),
      coronary artery disease (P = .0017), and New York Heart Association functional
      class (P = .012), with borderline value for atrial fibrillation (P = .10). The
      performance of valve repair was independently predictive of a lower incidence of
      the combined end point of death and heart failure (P = .001), compared with valve
      replacement. CONCLUSIONS: Congestive heart failure frequently occurs late after
      surgical correction of mitral regurgitation and portends dismal prognosis. This
      complication is due most often to left ventricular dysfunction; its main
      determinant is decreased left ventricular function preoperatively. These data
      should lead to earlier indication of surgical correction of mitral regurgitation,
      before left ventricular dysfunction occurs.

PMID- 7586352
TI  - Radionuclide monitoring of cardiac adaptations to volume loading in patients with
      dilated cardiomyopathy and mild heart failure. Effects of angiotensin-converting
      enzyme inhibition.
AB  - BACKGROUND: Cardiac adaptations to volume overload have been poorly investigated
      in heart failure. The aim of this study was to assess dynamic left ventricular
      responses to acute volume loading by continuous radionuclide monitoring in
      patients with asymptomatic to mildly symptomatic left ventricular dysfunction.
      METHODS AND RESULTS: Left ventricular end-diastolic (EDV) and end-systolic (ESV)
      volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a
      radionuclide detector (Vest) before and during volume expansion (sodium chloride,
      0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated
      cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I
      or II, ejection fraction < 50%). The patients were studied off treatment and
      after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of
      11 age- and sex-matched healthy volunteers (N group) was also studied. In the N
      group, volume loading caused prompt and sustained increases of EDV, EF, and PFR
      (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate
      and blood pressure did not change. In contrast, in DCM, EDV showed a smaller
      increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased
      (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac
      adaptations to volume loading were restored to normal. In particular, EDV, EF,
      and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM
      patients studied before and after 6 to 8 weeks of placebo treatment, left
      ventricular responses to volume loading remained unchanged. CONCLUSIONS: Left
      ventricular dynamic adaptations to acute volume loading are compromised in
      patients with idiopathic DCM and mild heart failure. These impaired responses are
      ameliorated by treatment with enalapril.

PMID- 7586353
TI  - Dilated cardiomyopathy associated with hepatitis C virus infection.
AB  - BACKGROUND: Myocarditis is thought to be commonly caused by various viruses, and
      accumulating evidence links viral myocarditis with the eventual development of
      dilated cardiomyopathy. In many cases, however, the evidence is only
      circumstantial, and direct conclusive proof is not available. Polymerase chain
      reaction (PCR) has been used to detect enterovirus RNA in myocardial tissue, but
      the wide discrepancy in results emphasizes the need for further study. METHODS
      AND RESULTS: We investigated hepatitis C virus infection in patients with dilated
      cardiomyopathy. The presence, type, and quantity of hepatitis C virus RNA were
      evaluated in the sera, and the presence of positive and negative strands of
      hepatitis C virus RNA in the heart was investigated with the PCR technique. Anti
      hepatitis C virus antibody was present in the sera of 6 of 36 patients (16.7%)
      with dilated cardiomyopathy and in 1 of 40 patients (2.5%) with ischemic heart
      disease, showing a statistically significant (P < .05) difference. At an earlier
      time, acute myocarditis was suspected in 3 patients who had developed acute onset
      of heart failure, and the diagnosis was confirmed by endomyocardial biopsy in 1
      patient. Hepatitis C virus RNA was present in the sera of 4 of the 6 patients,
      and all 4 had hepatitis C virus type II. The copy number of hepatitis C virus RNA
      in the serum was 8 x 10(2) to 2 x 10(3) genomes per 1 mL serum. Positive strands
      of hepatitis C virus were found in the hearts of 3 patients, and negative strands
      of hepatitis C virus were detected in the heart of 1 patient. CONCLUSIONS: The
      results suggest that hepatitis C virus infection is frequently found in patients
      with dilated cardiomyopathy and that hepatitis C virus is an important causal
      agent in the pathogenesis of the disease. Antiviral therapy against hepatitis C
      virus may be indicated in these patients.

PMID- 7586354
TI  - Sensitization of human atrial 5-HT4 receptors by chronic beta-blocker treatment.
AB  - BACKGROUND: Chronic treatment of patients with beta-blockers induces beta 2
      adrenergic receptor hyperresponsiveness in atrium and sinoatrial node. To
      investigate whether other atrial Gs protein-coupled receptors also become
      hyperresponsive after chronic treatment with beta-blockers, we investigated 5-HT4
      receptors in tissues and myocytes, which mediate serotonin-evoked increases of
      both contractile force and cAMP levels. METHODS AND RESULTS: Isolated right
      atrial strips from patients who had been chronically treated or not treated with
      a beta-blocker were set up to contract. In tissues from beta-blocker-treated
      patients (n = 27), the maximum inotropic response to serotonin was 56 +/- 3%
      (mean +/- SEM) of the effect elicited by (-)-isoproterenol (200 mumol/L) compared
      with a response of 19 +/- 6% in tissues from non-beta-blocker-treated patients (n
      = 13) (P < .001). The responsiveness of the tissues to Ca2+ was unchanged by
      chronic beta-blocker treatment. Serotonin (1 and 10 mumol/L) increased tissue
      cAMP levels, the increase with 10 mumol/L being significantly greater (P < .05)
      in tissues from beta-blocker-treated (n = 9) than in non-beta-blocker-treated (n
      = 7) patients. In paced atrial myocytes, serotonin caused concentration-dependent
      increases in contraction. Myocytes obtained from atria of beta-blocker-treated
      patients were more sensitive (P < .01) to the effects of serotonin (-log EC50,
      7.9 +/- 0.2 mol/L; n = 12) than myocytes obtained from non-beta-blocker-treated
      patients (-log EC50, 7.3 +/- 0.2 mol/L, n = 12). Chronic beta-blocker treatment
      had no effect on forskolin-evoked myocyte responses. Carbachol (1 mumol/L)
      suppressed the effects of both serotonin (n = 6) and (-)-isoproterenol (n = 6) in
      the same atrial myocyte. CONCLUSIONS: Chronic treatment of patients with beta
      blockers causes atrial 5-HT4 receptor inotropic hyperresponsiveness and enhanced
      serotonin-evoked increases in cAMP levels. This may be due to modified cross talk
      between 5-HT4 receptors, beta-adrenergic receptors, and muscarinic receptors.

PMID- 7586351
TI  - Effect of ryanodine on sarcoplasmic reticulum Ca2+ accumulation in nonfailing and
      failing human myocardium.
AB  - BACKGROUND: The purpose of this study was to determine whether abnormal Ca2+
      release through ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum
      might contribute to the abnormal [Ca2+]i homeostasis that has been described in
      failing human myocardium. METHODS AND RESULTS: Occupancy of low-affinity
      ryanodine binding sites on ryanodine-sensitive Ca2+ channels stimulates oxalate
      supported, ATP-dependent Ca2+ accumulation in sarcoplasmic reticulum-derived
      microsomes by inhibiting concurrent Ca2+ efflux through these channels. We
      examined the effects of 0.5 mmol/L ryanodine on 45Ca2+ accumulation in microsomes
      prepared from nonfailing (n = 8) and failing (n = 10) human left ventricular
      myocardium. In the absence of ryanodine, 45Ca2+ accumulation reached similar
      levels in microsomes from nonfailing and failing hearts. Incubation with 0.5
      mmol/L ryanodine caused a 52.2 +/- 6.5% increase in peak 45Ca2+ accumulation in
      microsomes from nonfailing hearts and a 24.3 +/- 4.1% increase in microsomes from
      failing hearts. The density of high-affinity ryanodine binding sites and the
      inhibition of [3H]ryanodine dissociation from these sites by 0.1 mmol/L ryanodine
      were similar in microsomes from nonfailing and failing hearts. CONCLUSIONS: These
      results, which demonstrate a diminished stimulation of Ca2+ accumulation by
      ryanodine in sarcoplasmic reticulum-derived microsomes from failing human
      myocardium that could be explained by an uncoupling of the occupancy of low
      affinity ryanodine binding sites from the reduction in the open probability of
      these channels or by concurrent Ca2+ efflux through a ryanodine-insensitive
      mechanism, are evidence that increased efflux of Ca2+ from the sarcoplasmic
      reticulum may contribute to the abnormal [Ca2+]i homeostasis described in failing
      human myocardium.

PMID- 7586355
TI  - Reduced contraction and altered frequency response of isolated ventricular
      myocytes from patients with heart failure.
AB  - BACKGROUND: Previous work has failed to demonstrate reduced maximal contraction
      of isolated ventricular myocytes from failing human hearts compared with
      nonfailing control hearts. The effect of alterations in stimulation frequency and
      temperature on the contraction of isolated ventricular myocytes has been
      investigated. Left ventricular myocytes were isolated from the hearts of patients
      with severe heart failure undergoing heart transplantation and compared with
      myocytes isolated from myocardial biopsies from patients with coronary disease
      but preserved left ventricular systolic function or from myocytes from rejected
      donor hearts. METHODS AND RESULTS: Myocytes were exposed to either a maximally
      activating level of extracellular calcium at 37 degrees C or to 2 mmol/L calcium
      at 32 degrees C. There was no significant difference in the contraction amplitude
      between myocytes from failing and nonfailing hearts at 0.2 Hz. With increasing
      stimulation frequency, there was a reduction in contraction amplitude in cells
      from failing hearts relative to control hearts in both maximal calcium from 0.33
      Hz (4.5% versus 6.6%) to 1.4 Hz (3.9% versus 8.8%) (ANCOVA, P < .001) and at 2
      mmol/L calcium from 0.50 Hz (2.3% versus 3.5%) to 1.4 Hz (1.8% versus 3.9%)
      (ANCOVA, P < .001). The time to peak contraction and the times to 50% and 90%
      relaxation were prolonged in myocytes from failing hearts at stimulation rate of
      0.2 Hz (P < .01), but only the time to 50% relaxation was prolonged at 1.0 Hz (P
      < .05). CONCLUSIONS: Reduced contraction, slowed relaxation, and impaired
      frequency response occurring at the level of the individual ventricular myocyte
      can be demonstrated in human heart failure. This demonstrates that disruption of
      myocyte function can contribute to both the systolic and the diastolic
      abnormalities that occur in the failing human heart.

PMID- 7586356
TI  - A randomized, placebo-controlled trial of propafenone in the prophylaxis of
      paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. UK
      Propafenone PSVT Study Group.
AB  - BACKGROUND: Few antiarrhythmic agents have been shown in randomized controlled
      trials to be effective and well tolerated in the prophylaxis of paroxysmal
      supraventricular tachycardia or paroxysmal atrial fibrillation. Propafenone, a
      class IC anti-arrhythmic agent with weak beta-adrenoceptor antagonist properties,
      has shown promise in preliminary clinical studies. METHODS AND RESULTS: A double
      blind, placebo-controlled trial of the efficacy and tolerability of propafenone
      was undertaken in 100 patients with paroxysmal supraventricular tachycardia
      ([PSVT] n = 52) or atrial fibrillation/flutter ([PAF] n = 48) who had recorded
      two or more symptomatic arrhythmia recurrences by transtelephonic ECG monitoring
      during a 3-month drug-free observation period. Patients were randomized into two
      consecutive crossover periods of propafenone (300 mg BID) versus placebo followed
      by 300 mg TID propafenone versus placebo. Analysis was based on the time to
      treatment failure, defined as the interval from treatment onset to the occurrence
      of either ECG-documented arrhythmia or an intolerable adverse event. With a
      proportional-hazards model, we determined the relative risk (95% confidence
      interval) of treatment failure after the achievement of steady-state drug levels
      for placebo compared with propafenone 300 mg BID to be 6.8 (2.2 to 21.2, P <
      .001, n = 45) for PSVT and 6.0 (1.8 to 20.0, P = .004, n = 30) for PAF. Due to a
      greater incidence of adverse events on high-dose propafenone, the relative risks
      of receiving placebo rather than propafenone 300 TID were only 2.2 (0.9 to 5.3, P
      = .1, n = 34) for PSVT and 1.9 (0.7 to 4.7, P = .2, n = 25) for PAF. However, if
      adverse events were excluded in the high-dose comparison, relative risks for
      arrhythmia recurrence were 15.0 (2.0 to 113, P = .009) for PSVT and incalculable
      (no preferences for placebo, P = .0002) for PAF. One episode of wide-complex
      tachycardia was documented during propafenone therapy. CONCLUSIONS: Propafenone
      is of value in the prophylaxis of both PSVT and PAF. A dose of 300 mg BID is
      effective and well tolerated. A larger dose of 300 mg TID causes more adverse
      effects but may be more effective in those who can tolerate it.

PMID- 7586357
TI  - Determination of ventricular vulnerable period and ventricular fibrillation
      threshold by use of T-wave shocks in patients undergoing implantation of
      cardioverter/defibrillators.
AB  - BACKGROUND: This study was designed to characterize the ventricular vulnerable
      period (VVP) and ventricular fibrillation (VF) threshold by use of T-wave shocks
      in patients undergoing implantation of cardioverter/defibrillators. A premature
      condensed shock applied during the VVP can induce VF. Most studies on the VVP and
      VF threshold have been conducted in animals rather than in humans. METHODS AND
      RESULTS: Twenty-one patients undergoing implantation of Medtronic PCD Jewel 7219D
      cardioverter/defibrillators because of ventricular tachycardia and/or VF were
      enrolled. All had structural heart disease. Their ages ranged from 42 to 85 years
      (mean, 69 +/- 11.3 years). Seventeen (80.9%) had atherosclerotic coronary artery
      disease. The right ventricle (RV) was driven at a cycle length (S1) of 400 ms,
      and monophasic shocks (S2) of 0.6 J were delivered through an RV apex lead
      (cathode) and a superior vena cava lead (anode) during the T wave of each cardiac
      cycle. The longest and shortest S1-S2 intervals that were capable of inducing
      sustained VF were defined as the outer and inner limits of the VVP at an energy
      level of 0.6 J, respectively. To determine the VF threshold, a shock of 0.2 J was
      applied at the midpoint of the VVP at 0.2-J increments until sustained VF was
      induced. The lowest energy setting capable of inducing sustained VF was defined
      as the VF threshold. Of the 21 patients, the VVP at an energy level of 0.6 J
      averaged 53.8 +/- 26.0 ms. Characteristically, the VVP started from the ascending
      limb of the T wave and ended at or slightly beyond the peak of the T wave,
      occupying 12.2 +/- 5.8% of the QT interval. The midpoint of the VVP used for
      determination of the VF threshold measured 0 to 90 ms (mean, 32.9 +/- 26.0 ms)
      before the peak of the T wave. Of the 21 patients, 16 (76.2%) had a VF threshold
      at < or = 0.2 J (estimated 57 V), 3 at 0.4 J (estimated 81 V), and 2 at 0.6 J
      (estimated 99 V). CONCLUSIONS: The VF threshold is low (< or = 0.2 J) in the
      majority of patients requiring implantation of cardioverter/defibrillators.
      Further studies are needed to define clinical usefulness of the study technique
      relative to its potential role for risk stratification and for assessing
      antifibrillatory properties of antiarrhythmic drugs in this subset group of
      patients.

PMID- 7586358
TI  - Primary ventricular fibrillation is associated with increased paced right
      ventricular electrogram fractionation.
AB  - BACKGROUND: The mechanisms of spontaneous ventricular fibrillation (primary VF)
      in patients without structural heart disease are obscure. A new technique has
      shown that in patients with hypertrophic cardiomyopathy conduction of
      fractionated ventricular paced beats, recorded at several right ventricular
      sites, is prolonged in individuals who have suffered a VF arrest, and this may
      reveal one component of a reentrant substrate. Patients with primary VF were
      studied with the same methods to determine whether similar abnormalities are
      present in this group. METHODS AND RESULTS: Nine patients with primary VF were
      studied by pacing one right ventricular (RV) site by use of a constant drive
      train with an extrastimulus inserted every third beat and reducing the
      extrastimulus coupling interval (S1S2 interval) by 1 ms on each occasion while
      recording at three other sites. The delay of each fractionated potential in the
      high-pass-filtered electrograms in response to the extrastimulus was determined
      and used to form conduction curves of delay versus the S1S2 interval. These
      curves were repeated by pacing each RV site in turn and recording from the other
      three sites. The curves were characterized by determining the S1S2 interval at
      which electrogram components increased in delay by 0.75 ms/20 ms reduction in
      S1S2 interval and the increase in electrogram duration between a coupling
      interval of 350 ms and 1 ms above refractoriness. Seven control patients were
      studied using the same method. The mean increase in electrogram duration in VF
      patients was 13 ms (range, 3 to 23 ms) compared with 4 ms (range, -2 to 14 ms) in
      unaffected control patients. The extrastimulus coupling interval at which delay
      increased was 318 ms (range, 293 to 334 ms) in VF patients and 274 ms (range, 265
      to 284 ms) in control patients (P < .01). There was no difference between the
      number of fractionated potentials in VF patients and control patients.
      CONCLUSIONS: In primary VF patients, the individual potentials within
      fractionated electrograms have increased delays when compared with control
      patients. This may identify one component of a reentrant arrhythmic substrate.

PMID- 7586359
TI  - Activation of blood coagulation after cardiac arrest is not balanced adequately
      by activation of endogenous fibrinolysis.
AB  - BACKGROUND: Animal studies have demonstrated that hemostatic disorders occurring
      after cardiac arrest affect outcome. We investigated hemostatic changes during
      and after cardiopulmonary resuscitation (CPR) in humans. METHODS AND RESULTS: The
      prospective study included 23 patients (29 to 86 years) who underwent out-of
      hospital CPR for nontraumatic causes. Blood samples were drawn immediately and 15
      and 30 minutes after initiation of CPR. In the case of restoration of spontaneous
      circulation (ROSC; n = 7), additional blood samples were taken immediately, 30
      minutes, and 2, 8, 24, 48, and 72 hours after ROSC. A marked activation of blood
      coagulation was found in all patients. The specific markers of activated blood
      coagulation and fibrin formation, thrombin-antithrombin complex (TAT; median
      during CPR, 260 micrograms/L; median after ROSC, 57 micrograms/L; normal range,
      1.0 to 4.1 micrograms/L), and fibrin monomers (FM; median during CPR, 34.3
      micrograms/mL; median after ROSC, 65.4 micrograms/mL; normal range, 0 to 3.6
      micrograms/mL) were markedly increased during and in the early phase after CPR.
      When patients survived for 48 hours, TAT and FM values returned to the normal
      range. In most patients, the plasma levels of D-dimer, an indicator of endogenous
      fibrinolytic activity, were not markedly increased during CPR (median, < 0.25
      microgram/mL; normal range, < 0.25 microgram/mL) but increased moderately after
      ROSC (median, 0.56 microgram/mL). Levels of plasminogen activator inhibitor type
      1 (normal range, 0.3 to 3.5 U/mL), a marker for endogenous inhibition of
      fibrinolytic activity, were moderately increased in most patients (median during
      CPR, 4.22 U/mL; median after ROSC, 8.08 U/mL). CONCLUSIONS: Our data clearly
      demonstrate that there is a marked activation of blood coagulation and fibrin
      formation after prolonged cardiac arrest and CPR in humans that is not balanced
      adequately by concomitant activation of endogenous fibrinolysis. These changes
      may contribute to reperfusion disorders, such as the cerebral "no-reflow"
      phenomenon, by inducing fibrin deposition and formation of microthrombi.

PMID- 7586360
TI  - Effects on coagulation and fibrinolysis with reduced versus full systemic
      heparinization and heparin-coated cardiopulmonary bypass.
AB  - BACKGROUND: Extracorporeal circulation with circuits coated with surface-bound
      heparin has allowed reduced levels of systemic heparinization. Clinical benefits
      have included reduced postoperative bleeding and less homologous blood usage.
      However, the effects on the hemostatic and fibrinolytic systems have remained in
      part unknown. METHODS AND RESULTS: Indications of thrombin generation, platelet
      activation, and fibrinolytic activity were investigated in patients undergoing
      coronary artery bypass surgery. Two groups were perfused with cardiopulmonary
      bypass (CPB) circuits completely coated with surface-bound heparin: one group
      with low systemic heparin dose (activated clotting time [ACT] > 250 seconds; n =
      17) and a second group having a full heparin dose (ACT > 480 seconds; n = 18). A
      third control group was perfused with ordinary uncoated circuits and full heparin
      dose (n = 17). The plasma level of thrombin-antithrombin complex and prothrombin
      fragment 1.2 increased in all groups during bypass, and somewhat more in both the
      heparin-coated groups toward the end of CPB, compared with the control group (P <
      .01). However, the increase during CPB was minimal compared with the major
      elevation observed 2 hours after surgery in all groups. Platelet release of beta
      thromboglobulin increased in all groups (P < .01) during CPB and significantly
      more in the high-dose group compared with the other two groups (P = .03).
      Fibrinolytic activities were similar in all groups, and there were no indications
      of major consumption of coagulation factors. CONCLUSIONS: Reduced systemic
      heparinization (ACT > 250 seconds) in patients having extracorporeal circulation
      with completely heparin-coated circuits did not lead to increased
      thrombogenicity. Thrombin formation remained within low ranges during CPB
      compared with patients receiving a full heparin dose and with the major
      elevations observed after surgery.

PMID- 7586362
TI  - Cytomegalovirus antigen expression, endothelial cell proliferation, and intimal
      thickening in rat cardiac allografts after cytomegalovirus infection.
AB  - BACKGROUND: Cardiac allograft arteriosclerosis is the primary cause of late death
      in heart transplant recipients. Clinical studies have suggested that humoral and
      cellular immune response, hyperlipidemia, and cytomegalovirus (CMV) infection may
      amplify the disease. In this study, the role of CMV infection in the development
      of rat cardiac allograft arteriosclerosis is investigated. METHODS AND RESULTS:
      Heterotopic rat cardiac allografts were performed from the DA to the WF rat
      strains. To prevent rejection, the recipients received triple-drug (cyclosporine
      A 20 mg.kg-1.d-1, azathioprine 2 mg.kg-1.d-1, and methylprednisolone 0.5 mg.kg
      1.d-1) immunosuppression postoperatively. Recipient rats were infected
      intraperitoneally (n = 21) with 10(5) plaque-forming units of rat CMV (RCMV) 1
      day after transplantation or were left uninfected and used as controls (n = 18).
      The grafts were removed 7 and 14 days and 1 and 3 months after transplantation.
      In 42% (9 of 21) of cardiac allografts in RCMV-infected rats, an intramural,
      mononuclear cell inflammation of small intramyocardial arterioles was observed
      compared with none in uninfected rats (P = .005). Acute RCMV infection was
      associated with an early perivascular inflammatory cell response of helper T
      (W3/25), cytotoxic T (OX8), and NK (3.2.3) cells, macrophages (OX42), and major
      histocompatibility complex class II expression around small intramyocardial
      arterioles and capillaries. No upregulation of interleukin-2 receptor expression
      was seen. In arteries and small intramyocardial arterioles, RCMV infection was
      associated with a significant endothelial cell proliferation and a clear increase
      in intimal thickening. Significant endothelial cell proliferation was also
      observed in the capillaries after RCMV infection. Immunohistochemistry revealed
      specific focal RCMV early and late antigen expression in epicardial and
      interstitial ED1-immunoreactive mononuclear cell infiltrates and around small
      arterioles of RCMV-infected cardiac allografts. Occasionally, media cells of
      stenosed small intramyocardial arterioles also showed strong focal RCMV antigen
      expression. In addition, infectious RCMV could be recovered by plaque assay in
      cardiac allografts expressing RCMV antigens. CONCLUSIONS: These results
      demonstrate a productive RCMV infection in cardiac allograft structures and
      suggest that RCMV infection accelerates cardiac allograft arteriosclerosis,
      particularly in small intramyocardial arterioles mediated by inflammatory
      responses in the vascular wall and perivascular space.

PMID- 7586361
TI  - Effects of disruption of the plasminogen gene on thrombosis, growth, and health
      in mice.
AB  - BACKGROUND: Circumstantial evidence suggests that the plasminogen/plasmin system
      plays a role in many biological processes, including hemostasis, cell migration,
      and development. METHODS AND RESULTS: The in vivo function of the
      plasminogen/plasmin system was studied by generation of plasminogen-deficient
      (Plg-/-) mice. Inactivation of the murine plasminogen-gene (Plg) was achieved by
      replacing, via homologous recombination in embryonic stem cells, genomic
      sequences encoding the exons containing the catalytic site amino acids His605 and
      Asp648 with a neomycin phosphotransferase expression cassette. Germline
      transmission of the mutated allele, as determined by Southern blot hybridization
      and polymerase chain reaction, was obtained via blastocyst injection. Mendelian
      inheritance of the inactivated plasminogen allele was observed, and homozygous
      deficient mice (Plg-/-) displayed normal viability but retarded growth up to at
      least 12 weeks of age. At 8 weeks of age, body weight was 21.8 +/- 1.2 g (n = 10)
      for wild-type (Plg+/+) mice, 21.0 +/- 1.1 g (n = 16) for heterozygous-deficient
      (Plg+/-) mice, and 17.4 +/- 1.3 g (n = 12) for Plg-/- mice; P < .05 versus Plg+/+
      or Plg+/-. None of 36 Plg+/+ or 65 Plg+/- mice but 7 of 37 Plg-/- mice (19%)
      developed rectal prolapse at 7.4 +/- 0.6 weeks of age (P = .03 versus Plg+/+ and
      P = .003 versus Plg+/-); 4 of 37 Plg-/- mice (11%) became runted and apathic at
      5.3 +/- 0.3 weeks of age (P = .041 versus Plg+/-); and 6 of 37 Plg-/- mice (16%)
      died prematurely at 8.8 +/- 1.7 weeks of age (P = .057 versus Plg+/+ and P = .029
      versus Plg+/-). Although male and female Plg-/- mice were able to sire offspring,
      the fertility of Plg-/- female mice was reduced, possibly owing to their impaired
      health. Levels of plasminogen-related antigen in plasma, measured by ELISA, were
      84 +/- 8 micrograms/mL (n = 4) in Plg+/+, 35 +/- 2 micrograms/mL (n = 3) in Plg+/
      , and 0.076 +/- 0.032 microgram/mL (n = 6) in Plg-/- mice (P < .001 versus Plg+/-
      and Plg+/+). Plasmin activity generated by urokinase activation was unmeasurable
      in Plg-/- mice (< 5% of Plg+/+ mice). Plasminogen-specific immunoreactivity was
      observed in hepatocytes from Plg+/+ mice but not from Plg-/- mice (< 10% of
      Plg+/+ mice). Neither native nor variant plasminogen mRNA nor translation
      products could be identified by Northern or Western blot of liver extracts from
      Plg-/- mice. Spontaneous lysis within 24 hours of a 125I-fibrin-labeled pulmonary
      plasma clot was 85 +/- 5% (n = 5) in Plg+/+ mice, 62 +/- 7% (n = 3) in Plg+/-
      mice, and -2 +/- 1% (n = 3) in Plg-/- mice (P < .001 versus Plg+/- and Plg+/+).
      Delayed clot lysis within 72 hours was 33 +/- 1% (n = 3) in tPA-/- mice and 26 +/
      2% (n = 3) in Plg-/- mice (P = .054). Histological examination of several organs
      revealed fibrin deposition in the liver; lung; and in the stomach, associated
      with gastric ulcers, in 6- to 12-week-old Plg-/- mice but not in Plg+/+ or Plg+/-
      littermates. CONCLUSIONS: Plasminogen-deficient mice survive embryonic
      development but develop spontaneous fibrin deposition due to impaired
      thrombolysis and suffer retarded growth and reduced fertility and survival. The
      Plg-/- phenotype is reminiscent of the combined tPA-/-:uPA-/- phenotype, which
      suggests that there is no significant additional pathway for physiological
      plasminogen activation in mice.

PMID- 7586363
TI  - Seeding with omental cells prevents late neointimal hyperplasia in small-diameter
      Dacron grafts.
AB  - BACKGROUND: The influence of complete endothelialization of a prosthetic graft on
      development of late neointimal hyperplasia is unknown. This study was designed to
      investigate the effect of complete coverage with endothelial-like cells on late
      neointimal hyperplasia in small-diameter Dacron grafts seeded with omental cells
      in a canine model. METHODS AND RESULTS: Four-mm-ID Dacron grafts were seeded with
      cells from omentum and implanted in the carotid arteries in 24 mongrel dogs. Each
      dog received one seeded and one nonseeded graft. The graft patencies were
      assessed by angiography at 1, 5, 12, 26, and 52 weeks after surgery. The
      prostheses were explanted at 5, 12, 26, and 52 weeks after surgery and underwent
      microscopic studies. The actuarial patency rates at 1, 5, 12, 26, and 52 weeks
      were 100%, 95%, 95%, 95% and 95% for seeded grafts and 100%, 86%, 49%, 40%, and
      13% for nonseeded grafts, respectively. The seeded grafts exhibited a uniform
      endothelial-like luminal monolayer without the development of late neointimal
      proliferation or anastomotic neointimal hyperplasia. Neointimal tissue thickness
      increased up to 6 months; no additional progression of the subendothelial tissue
      thickness was observed, in fact there was an insignificant decrease. CONCLUSIONS:
      Seeding with omental cells prevents development of late neointimal hyperplasia of
      small diameter prosthetic vascular grafts in a canine model.

PMID- 7586364
TI  - Magnesium sulfate reduces myocardial infarct size when administered before but
      not after coronary reperfusion in a canine model.
AB  - BACKGROUND: The role of magnesium in treating acute myocardial infarction (AMI)
      has been controversial. Several small clinical trials indicate that magnesium may
      have a role in treating AMI early, whereas the other results suggest that
      magnesium is of questionable benefit. METHODS AND RESULTS: We looked at the
      effect of magnesium on infarct size (IS) when given during a coronary occlusion
      and after reperfusion. Magnesium sulfate (6-mEq bolus plus 2 mEq/h for 5 hours)
      was given at 15 or 45 minutes of coronary occlusion or 15 minutes of reperfusion.
      The left anterior descending coronary artery was occluded for 90 minutes,
      followed by 300 minutes of reperfusion. IS to area at risk (IS/AR) was measured
      by planimetry after triphenyltetrazolium chloride staining. Collateral myocardial
      blood flow was measured with radioactive microspheres. The IS/AR ratio in the
      control group was 52.3 +/- 19.6% compared with 20.5 +/- 11.7% and 21.3 +/- 6.5%
      at 15 and 45 minutes of occlusion, respectively (P < .05). There were no
      significant differences in the reduction in IS at 15 and 45 minutes of occlusion.
      Although there was a reduction in the IS when magnesium was administered during
      reperfusion (38.2 +/- 13.4%), it was not statistically significant. There was no
      significant difference in the AR relative to the total left ventricular weight
      between the four groups. CONCLUSIONS: The data suggest that magnesium infusion
      during a coronary occlusion has a significant benefit in reducing the IS in this
      model. Magnesium may have a beneficial clinical role in AMI, especially if
      administered before reperfusion as a bolus followed by a constant infusion.

PMID- 7586365
TI  - Timing of magnesium therapy affects experimental infarct size.
AB  - BACKGROUND: Controversy exists regarding the use of magnesium in the treatment of
      acute myocardial infarction (AMI) because of apparent conflicting results from
      clinical trials. One hypothesis to explain the various clinical observations
      proposes that the timing of magnesium administration significantly influences its
      therapeutic effect; ie, supraphysiological levels of Mg2+ must be present at the
      time of reperfusion for magnesium to produce clinical benefit. METHODS AND
      RESULTS: These experiments evaluated the effect of varying the timing of
      magnesium administration during AMI. Female Yorkshire swine (34 to 42 kg)
      underwent thoracotomy and 50 minutes of left anterior descending coronary artery
      (LAD) occlusion, followed by 3 hours of reperfusion. In the first group, MgSO4
      (250 mg of magnesium diluted in 60 cm3 saline) was infused into the LAD over 12
      minutes, beginning immediately with the onset of reperfusion (n = 6, Mg-early
      group). In the second group, MgSO4 was given after 1 hour of reperfusion (n = 6,
      Mg-late group). Six pigs received saline instead of magnesium and served as the
      control group. Lethal arrhythmias were significantly reduced in the Mg-early
      group. Infarct size was determined by vital staining. Infarct size was 0.16 +/-
      0.05 g/kg body wt (Mg-early), 0.35 +/- 0.08 g/kg (Mg-late), and 0.42 +/- 0.04
      g/kg for the control group. Compared with the control group, significant (P =
      .029) reduction in infarct size occurred in the Mg-early group but not in the Mg
      late group. CONCLUSIONS: We conclude that intracoronary MgSO4 delivered during
      reperfusion can significantly diminish infarct size in swine, but the timing of
      administration is critical.

PMID- 7586366
TI  - Endothelial modulation of beta-adrenergic dilation of large coronary arteries in
      conscious dogs.
AB  - BACKGROUND: Endothelium-derived relaxing factors have been described as important
      intermediates in beta-adrenergic vasodilation of resistance coronary vessels, but
      their involvement at the level of large epicardial coronary arteries remains
      controversial. Therefore, we examined the role of vascular endothelium in the
      beta-adrenergic-mediated vasodilation of large epicardial coronary arteries in
      conscious dogs. METHODS AND RESULTS: Nine dogs were instrumented for measurement
      of left circumflex coronary artery diameter (CD) by sonomicrometry and coronary
      blood flow velocity (CBFv) with a Doppler technique in response to graded doses
      of isoproterenol (0.001 to 0.1 microgram/kg IV bolus). Under control conditions,
      isoproterenol induced dose-dependent increases in CD and CBFv. When CBFv was kept
      constant at its baseline value by inflation of a cuff occluder, isoproterenol
      still induced dose-dependent increases in CD, but the latter were of lesser
      magnitude than those observed under normal CBFv conditions (110 +/- 20 versus 170
      +/- 30 microns, respectively, ie, a reduction of 33% of the dilatory response at
      0.1 microgram/kg, P < .01). In the same dogs, the coronary endothelium was then
      mechanically removed at the site of CD measurement by a balloon angioplasty
      technique. After this procedure, the dose-dependent increases in CD induced by
      isoproterenol under either normal or controlled CBFv conditions were
      overimposable, and their magnitude was similar to that of the increases observed
      in the presence of an intact endothelium when CBFv was kept constant. After beta
      1-adrenergic receptor blockade by atenolol (1 mg/kg), isoproterenol-induced
      increases in CD were abolished either when CBFv was kept constant or after
      endothelium removal. CONCLUSIONS: In conscious dogs, the direct stimulating
      effect of isoproterenol on beta 1-adrenergic receptors is endothelium-independent
      at the level of large coronary arteries. The endothelium reinforces the dilatory
      response to isoproterenol through an indirect, flow-dependent mechanism.

PMID- 7586367
TI  - Chronic inhibition of endothelium-derived nitric oxide synthesis causes coronary
      microvascular structural changes and hyperreactivity to serotonin in pigs.
AB  - BACKGROUND: Endothelium-derived nitric oxide (NO) is believed to regulate
      myocardial perfusion and structural changes in the vascular wall. Our objective
      was to determine whether chronic inhibition of NO synthesis causes structural and
      functional changes in coronary arteries. METHODS AND RESULTS: Coronary vasomotor
      response was studied in pigs before and after chronic oral administration of the
      NO synthesis antagonist N omega-nitro-L-arginine methyl ester (L-NAME) 30 mg.kg
      1.d-1 for 2 weeks. Chronic L-NAME treatment increased (P < .01) arterial pressure
      but did not alter baseline coronary blood flow (CBF), epicardial coronary
      diameter, or heart rate. Chronic L-NAME treatment augmented (P < .01) the
      decrease in CBF in response to intracoronary serotonin (30 micrograms/kg) from 5
      +/- 14% to 40 +/- 5% but did not alter the CBF response to prostaglandin F2
      alpha. The serotonin-induced decrease in CBF after acute L-NAME administration
      was still less before (1.3 +/- 0.4%) than after chronic L-NAME treatment (51 +/-
      6%). Chronic L-NAME treatment attenuated the increase in CBF with bradykinin (100
      ng/kg) but did not alter the CBF response to nitroglycerin (10 micrograms/kg).
      Compared with intact pigs without L-NAME treatment, L-NAME-treated pigs had
      significant thickening of the media in the microvessels (diameter, < 300 microns)
      but not in the large epicardial vessels. Chronic intracoronary infusion of L-NAME
      at 3 mg.kg-1.d-1 for 2 weeks, which did not produce arterial hypertension, caused
      similar microvascular medial thickening. CONCLUSIONS: These results indicate that
      chronic administration of L-NAME caused coronary microvascular structural changes
      and hyperreactivity to serotonin in pigs in vivo, suggesting an important role of
      defective NO synthesis in coronary microvascular disorders.

PMID- 7586368
TI  - Echocardiographic assessment of spontaneously occurring feline hypertrophic
      cardiomyopathy. An animal model of human disease.
AB  - BACKGROUND: Necropsy studies in domestic cats have suggested the occurrence of a
      primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans.
      We used two-dimensional echocardiography to define morphological and functional
      features of HCM during life in 46 domestic cats evaluated in a subspecialty
      veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years). METHODS
      AND RESULTS: During the follow-up period of as long as 49 months, 18 cats died
      (or were euthanatized) due to congestive heart failure, peripheral embolization,
      or both, and 3 other cats experienced out-of-hospital sudden, unexpected death.
      Echocardiography showed a small left ventricular cavity, associated with a
      variety of patterns of hypertrophy. Wall thickening was most often diffuse
      (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15
      (33%), including 12 with thickening confined to anterior septum; wall thickening
      was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats
      (65%), marked mitral valve systolic anterior motion produced dynamic obstruction
      to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg).
      Compared with survivors, cats with HCM that died with heart failure had greater
      left ventricular thickness (8.1 +/- 1.5 versus 7.3 +/- 0.9 mm; P < .05) and
      larger left atria (20.1 +/- 4.6 versus 16.8 +/- 3.4 mm; P = .01) and more often
      had the nonobstructive form (89% versus 48%; P < .01). CONCLUSIONS: A
      spontaneously occurring disease of domestic cats was identified by
      echocardiography and was similar in its phenotypic expression to HCM in humans;
      it was characterized by unexplained left ventricular hypertrophy in a variety of
      patterns with or without evidence of outflow obstruction. Unfavorable prognosis
      was associated with greater magnitude of hypertrophy and absence of outflow
      obstruction. Feline HCM may prove to be a valuable animal model of the human
      disease.

PMID- 7586369
TI  - Postextrasystolic mechanical restitution in closed-chest dogs. Effect of heart
      failure.
AB  - BACKGROUND: Postextrasystolic mechanical restitution (MRPES) is thought to be an
      expression of intracellular Ca2+ handling by cardiac sarcoplasmic reticulum (SR).
      Since congestive heart failure is characterized by abnormal intracellular Ca2+
      homeostasis, we sought to delineate MRPES behavior before and after the
      production of heart failure to obtain insights into the relation between altered
      mechanical performance and Ca2+ handling. METHODS AND RESULTS: Ten dogs
      instrumented with left ventricular (LV) micromanometers and piezoelectric
      dimension crystals were studied under control conditions; 6 dogs also were
      studied after tachycardia heart failure (THF) produced by rapid LV pacing for 4
      weeks. After priming at a basic cycle length of 375 ms, test pulses were
      delivered at fixed extrasystolic intervals (ESIs; 300, 375, or 450 ms) and graded
      postextrasystolic intervals (PESIs). Postextrasystolic mechanical response was
      assessed using single-beat elastance. MRPES curves were constructed by expressing
      normalized mechanical response as a function of the PESI. Control MRPES was a
      monoexponential function whose time constant (TC) and PESI-axis intercept (PESI0)
      increased significantly (P < .01) with increases in the antecedent ESI. THF
      significantly slowed MRPES kinetics at each antecedent ESI (P < .025), increased
      normalized maximal contractile response (CRmax, P < .01), and shortened PESI0 (P
      < .025). Increases in the TC and CRmax were most pronounced with the smallest
      antecedent ESI (percent control postextrasystolic TC 363.7 +/- 60.5%, ESI of 300
      ms versus 139.0 +/- 15.1%, ESI of 450 ms, P < .005; percent control CRmax 128.6
      +/- 4.9%, ESI of 300 ms versus 104.9 +/- 1.0%, ESI of 450 ms; P < .005).
      CONCLUSIONS: MRPES is much less dynamic in THF: The failing heart operates at
      lower levels of contractile performance after higher stimulation frequencies and
      cannot increase its speed of contractile recovery to compensate for higher heart
      rate. Prolongation of MRPES kinetics is consistent with depression of SR Ca2+
      release mechanisms in THF and implicates this site in the loss of the capacity of
      the failing heart to maintain mechanical performance with tachycardia.

PMID- 7586370
TI  - Enhancement of left ventricular relaxation in the isolated heart by an
      angiotensin-converting enzyme inhibitor.
AB  - BACKGROUND: ACE inhibitors exert both acute and chronic beneficial effects on
      cardiac function (eg, remodeling, diastolic dysfunction) in experimental studies
      and in patients. They inhibit the formation of angiotensin II as well as the
      degradation of endogenous bradykinin. We recently reported that bradykinin
      induces selective left ventricular (LV) relaxant effects in isolated hearts via
      the release of nitric oxide. The present study examined the direct effects of
      interaction between the ACE inhibitor captopril and endogenous bradykinin on
      cardiac contractile function. METHODS AND RESULTS: Isolated ejecting guinea pig
      hearts were studied under conditions of constant loading and heart rate. LV
      pressure was monitored by a 2F micromanometer-tipped catheter. Captopril (1
      mumol/L, n = 9) caused a progressive acceleration of LV relaxation without
      significantly affecting early systolic parameters (eg, LV dP/dtmax) or coronary
      flow. These effects were inhibited by the nitric oxide scavenger hemoglobin (1
      mumol/L, n = 5) or by the B2-kinin receptor antagonist HOE140 (10 nmol/L, n = 5).
      In the presence of captopril, bradykinin (0.1 nmol/L, n = 6) markedly accelerated
      LV relaxation (significantly more than captopril alone), whereas bradykinin alone
      (0.1 nmol/L, n = 6) had no effect. CONCLUSIONS: These data indicate that the ACE
      inhibitor captopril causes an acute and selective enhancement of LV relaxation
      independent of changes in coronary flow, probably via an endogenous
      bradykinin/nitric oxide pathway.

PMID- 7586371
TI  - Long-term treatment with angiotensin I-converting enzyme inhibitors attenuates
      the loss of cardiac beta-adrenoceptor responses in rats with chronic heart
      failure.
AB  - BACKGROUND: Cardiac contractile force in response to beta-adrenoceptor agonists
      and beta-adrenergic receptor density are decreased in failing human hearts. The
      effects of angiotensin I-converting enzyme (ACE) inhibitor on cardiac
      responsiveness to beta-adrenergic stimulation in failing hearts are not
      established. The present study was undertaken to determine whether ACE inhibitor
      may improve cardiac beta-adrenergic responsiveness in animals with chronic heart
      failure (CHF). METHODS AND RESULTS: CHF was induced by left coronary artery
      ligation in rats. Cardiac output and stroke volume indices decreased 12 weeks
      after the operation. In sham-operated rats, dobutamine and isoprenaline increased
      cardiac output and stroke volume indices. In contrast, cardiac output and stroke
      volume responses to dobutamine and isoprenaline were severely blunted in the CHF
      rat. Cardiac beta 1-adrenergic receptor density was decreased while its
      dissociation constant (Kd) was not altered in the viable tissue of the left
      ventricle of the CHF rat, which is consistent with beta-adrenergic receptor
      downregulation. Cardiac norepinephrine content decreased in the CHF rats. Rats
      were treated orally with ACE inhibitors, 3 mg/kg trandolapril or 10 mg/kg
      enalapril once daily, or 5 mg/kg captopril twice daily from the 2nd to the 12th
      weeks after the operation. Treatment with ACE inhibitors attenuated the reduction
      in cardiac output and stroke volume indices and improved the inotropic response
      to dobutamine and isoprenaline and reversed partially the cardiac norepinephrine
      content in the CHF rat. ACE inhibitor treatment also attenuated the reduction in
      beta 1-adrenergic receptor density in the viable tissue of the left ventricle of
      the CHF rat. CONCLUSIONS: The results suggest that ACE inhibitor treatment
      attenuates the blunting of cardiac responses to beta-adrenergic agonists in the
      CHF rat and that one of the mechanisms underlying this effect is prevention of
      cardiac beta 1-adrenergic receptor downregulation.

PMID- 7586372
TI  - Detection of regional left ventricular dysfunction in early pacing-induced heart
      failure using ultrasonic integrated backscatter.
AB  - BACKGROUND: It has been demonstrated that cyclic variation of ultrasonic
      integrated backscatter (CVIBS) may be useful in detecting altered physical
      conditions in the heart. However, no previous study has examined serial changes
      of CVIBS in the myocardium during the development of left ventricular
      dysfunction. METHODS AND RESULTS: We examined alterations of CVIBS in pacing
      induced cardiac dysfunction. Eight pigs (36 +/- 2 kg) were studied before and
      sequentially during sustained rapid ventricular pacing (225 +/- 9 beats per
      minute). CVIBS was measured in the IVS and left ventricular PLW before pacing and
      daily for 4 days after onset of pacing. Five additional pigs (35 +/- 10 kg) were
      examined after 14 days of pacing. Regional function and CVIBS were assessed with
      pacemakers inactivated. A quantitative integrated backscatter imaging system (two
      dimensional format) was used. Over 4 days of pacing, the magnitude of CVIBS
      progressively decreased in the PLW but was unchanged in the IVS, findings that
      persisted at 14 days. Percent wall thickening in the PLW progressively decreased
      to a greater degree than percent wall thickening in the IVS. A linear relation
      between the magnitude of CVIBS and percent wall thickening was found. At 14 days,
      blood flow to the two regions was similar but regional differences in CVIBS
      persisted. CONCLUSIONS: Rapid left ventricular pacing produces abnormalities of
      regional myocardial function within 48 hours of pacing. Regional myocardial
      dysfunction is accompanied by a reduction in CVIBS in the same region.

PMID- 7586373
TI  - Angiotensin II augments cytokine-stimulated nitric oxide synthesis in rat cardiac
      myocytes.
AB  - BACKGROUND: Nitric oxide (NO) has been shown to modulate cardiac function. We
      investigated the effect of angiotensin II (Ang II) on NO synthase activity in
      cardiac myocytes. METHODS AND RESULTS: Using the Griess reagent, we measured the
      production of nitrite, a stable metabolite of NO, by cultured neonatal rat
      cardiac myocytes. The expression of inducible NO synthase (iNOS) mRNA was assayed
      by Northern blotting. Incubation of cardiac myocytes for 24 hours with
      interleukin-1 beta (IL-1 beta) caused a significant increase in NO production.
      Ang II significantly augmented NO synthesis in IL-1 beta-stimulated but not in
      unstimulated cells in a dose-dependent manner. The angiotensin type I receptor
      antagonist CV 11974 inhibited the effect of Ang II dose-dependently. Simultaneous
      incubation of Ang II with NG-monomethyl-L-arginine or actinomycin D also
      completely inhibited the effect of Ang II. The Ang II-induced NO production by IL
      1 beta-stimulated cells was accompanied by increased iNOS mRNA accumulation.
      Phorbol 12-myristate 13-acetate (PMA) also augmented NO synthesis in IL-1 beta
      stimulated but not in unstimulated cells in a dose-dependent manner. The protein
      kinase C inhibitor calphostin C dose-dependently blocked the effect of Ang II.
      After protein kinase C activity was functionally depleted by treatment of cells
      with PMA for 24 hours, Ang II did not augment IL-1 beta-induced NO production.
      CONCLUSIONS: These results indicate that Ang II upregulates IL-1 beta-induced
      iNOS expression in cardiac myocytes, which is mediated at least partially via
      activation of protein kinase C.

PMID- 7586375
TI  - Combining monophasic action potential recordings with pacing to demonstrate
      delayed afterdepolarizations and triggered arrhythmias in the intact heart. Value
      of diastolic slope.
AB  - BACKGROUND: In the intact heart, methodological difficulties hamper the direct
      visualization of delayed afterdepolarizations (DADs) responsible for triggered
      arrhythmias. Therefore, we tested the hypothesis that a combination of pacing and
      the recording of a monophasic action potential (MAP) could facilitate the
      recognition of ouabain-induced DADs and triggered arrhythmias by demonstrating an
      increase in the diastolic baseline slope (dV/dT) of the MAP recording at the end
      of a pacing train. METHODS AND RESULTS: In anesthetized dogs with chronic
      atrioventricular block, a right ventricular endocardial MAP was recorded during
      (1) control (n = 11), (2) 15 to 45 minutes after administration of ouabain (45 +/
      10 micrograms/kg, n = 11), (3) 10 minutes after administration of lidocaine (3
      mg/kg, n = 5), and (4) during lidocaine washout (n = 3). Pacing was performed
      with the MAP catheter. Also, the protocol was performed in 3 dogs with conducted
      sinus rhythm during control and ouabain circumstances. During control, the slope
      value was 2 +/- 2 mV/s (mean +/- SD), the incidence of DADs after the stimulation
      train was 6%, and no ventricular tachycardias (VTs) were induced in dogs with
      atrioventricular block. During ouabain administration, the slope and DAD
      incidences increased to, respectively, 26 +/- 14 mV/s and 74% (P < .05 for both).
      VTs were induced frequently. Lidocaine prevented VT induction by decreasing the
      slope and the incidence of DADs. This effect disappeared after lidocaine washout.
      During conducted sinus rhythm, similar results were found. CONCLUSIONS: By
      combining pacing and MAP recordings, the diastolic slope observed on MAP
      recordings in ouabain-intoxicated hearts can be used as a marker for DADs and
      triggered arrhythmias. This finding may be helpful in identifying triggered
      activity in the intact heart.

PMID- 7586376
TI  - Atrioventricular nodal conduction gap and dual pathway electrophysiology.
AB  - BACKGROUND: The gap phenomenon in atrioventricular (AV) conduction is described
      as a block that occurs within a range of atrial coupling intervals. This block is
      assumed to occur between two adjacent parts of the conduction system having
      different refractory properties; thus, a gap would develop if the functional
      refractory period of the proximal unit was shorter than the effective refractory
      period of the distal unit. We describe a new electrophysiological mechanism based
      on dual pathways electrophysiology of the AV node. METHODS AND RESULTS: In vitro
      experiments were performed on isolated superfused rabbit hearts. Standard
      electrophysiological pacing and recording techniques were used to generate
      conduction curves. The gap phenomenon was documented in 9 of 14 nodal
      preparations. With shortening of the atrial coupling interval, antegrade
      conduction block of the "fast" pathway wave front occurred while this impulse was
      still retrogradely interfering with slow pathway conduction. That is, the fast
      pathway wave front prevented propagation of the anterograde "slow" pathway wave
      front by collision or by creating a refractory barrier. This mechanism produced a
      gap and the block persisted until, at even shorter coupling intervals, the fast
      wave front penetration became insufficient and conduction was restored through
      the released slow pathway wave front. This mechanism was verified in AV nodal
      preparations with separated inputs, in which independent fast and slow wave
      fronts could be induced and programmed to collide. CONCLUSIONS: Our results
      established the functional interaction of fast and slow pathway wave fronts as an
      important electrophysiological mechanism underlying the AV conduction gap. This
      mechanism may be responsible for a variety of clinically observed conduction
      discontinuities.

PMID- 7586374
TI  - Cardiac renin-angiotensin system in the hypertrophied heart.
AB  - BACKGROUND: The cardiac renin-angiotensin system (RAS) has been suggested to play
      an important role in heart failure and cardiac hypertrophy. In the present study,
      we evaluated the expression of each component of the RAS in hypertrophied heart
      induced by aortocaval shunt. METHODS AND RESULTS: The expression levels of renin,
      angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type Ia
      and Ib receptor (AT1aR and AT1bR) mRNA were determined by the reverse
      transcription-polymerase chain reaction method owing to the relatively low
      expression levels of these mRNAs in the ventricle. The expression level of renin
      or angiotensinogen mRNA in the ventricle was very low, more than 1000-fold lower
      than that in the kidney or liver, respectively. The expression of ACE mRNA in the
      ventricle was relatively abundant and was increased in the hypertrophied
      ventricle in this model, whereas no significant increases in the expression
      levels of AT1aR and AT1bR mRNA were observed. Administration of lisinopril
      attenuated the development of left and right ventricular hypertrophy in this
      model and was accompanied by an attenuation of the upregulation of the ACE,
      collagen type I-alpha, and vimentin mRNAs. Because the activity of the
      circulating RAS in the aortocaval shunt rats was not higher than that in the sham
      operated rats, the effects of lisinopril in attenuating the ventricular
      hypertrophy may be due to inhibition of the increased ACE in the ventricle.
      CONCLUSIONS: The present study supports the importance of ACE expressed in the
      ventricle in the development of hypertrophy induced by aortocaval shunt.

PMID- 7586377
TI  - The pathogenic role of Staphylococcus epidermidis capsular polysaccharide/adhesin
      in a low-inoculum rabbit model of prosthetic valve endocarditis.
AB  - BACKGROUND: The capsular polysaccharide/adhesin (PS/A) antigen of Staphylococcus
      epidermidis was required to produce endocarditis in a rabbit model in which
      infection resulted from hematogenous spread of bacteria from a contaminated
      catheter in the jugular vein. However, many prosthetic valve endocarditis (PVE)
      infections probably result from direct contamination of the valve with small
      numbers of bacteria during surgery. The role of PS/A in this situation was
      evaluated by modifying a rabbit model of endocarditis to partially mimic PVE.
      METHODS AND RESULTS: A Teflon catheter was contaminated with graded inocula of
      either PS/A-positive S epidermidis strain M187sp11 or the PS/A-negative, isogenic
      strain M187sn3 and inserted into the left ventricle through the aortic valve. The
      PS/A-positive strain had a 50% infectious dose of 1.1 x 10(2) cfu (95% CI, 3.3 to
      3.7 x 10(3)) compared with 8.5 x 10(4) cfu of the PS/A-negative strain (95% CI,
      8.6 x 10(3) to 8.5 x 10(5)). The odds for developing endocarditis were estimated
      to be 42 times higher for any given inoculum level of the PS/A-positive strain (P
      = .1). When the PS/A-positive strain was adherent to a catheter surface it
      survived in rabbit blood, whereas under the same conditions the PS/A-negative
      strain was killed approximately 90% in 1 hour. CONCLUSIONS: Direct contamination
      of an intraventricular foreign body by low levels of PS/A-positive S epidermidis
      results in endocarditis in rabbits, but at suitably high doses PS/A-negative
      strains have sufficient virulence to infect cardiac vegetations. PS/A enhances
      but is not absolutely required for bacterial virulence in a rabbit model of PVE.

PMID- 7586378
TI  - Magnetic resonance imaging in coronary artery disease.
AB  - The cardiovascular applications of nuclear magnetic resonance (MR) techniques in
      coronary artery disease have increased considerably in recent years. Technical
      advantages of MR imaging in comparison with other techniques are the excellent
      spatial resolution, the characterization of myocardial tissue, and the potential
      for three-dimensional imaging. This allows the accurate assessment of left
      ventricular mass and volume, the differentiation of infarcted tissue from normal
      myocardial tissue, and the determination of systolic wall thickening and regional
      wall motion abnormalities. Myocardial perfusion, metabolism, and inducible
      myocardial ischemia with the use of pharmacological stress also can be assessed
      by MR techniques. Future technical improvements in real-time imaging and
      development of noninvasive visualization of the coronary arteries and coronary
      artery bypasses will constitute a tremendous progress in clinical cardiology.
      Early detection and flow assessment of stenosed coronary arteries by MR
      angiography with the use of flow velocity measurements may outweigh the cost
      inherent to the MR imaging procedure. A particular strength of the MR technique
      is the potential to encompass cardiac anatomy, perfusion, function, metabolism,
      and coronary angiography in a single test. The replacement of multiple diagnostic
      tests with one MR test may have major effects on cardiovascular healthcare
      economics.

PMID- 7586379
TI  - American Heart Association Report on the Public Access Defibrillation Conference
      December 8-10, 1994. Automatic External Defibrillation Task Force.

PMID- 7586380
TI  - Images in cardiovascular medicine. Extreme left ventricular hypertrophy.

PMID- 7586381
TI  - Unique ionic mechanism of action of ibutilide on freshly isolated heart cells.

PMID- 7586382
TI  - Acute ischemic syndromes.

PMID- 7586383
TI  - Temporal changes in myocardial perfusion patterns after AMI.

PMID- 7586385
TI  - Long-term effects of angiopeptin treatment in coronary angioplasty: reduction of
      clinical events but not angiographic restenosis.

PMID- 7586384
TI  - Cardioprotective effect of C1-inhibitor.

PMID- 7586387
TI  - Bedside science reduces laboratory art.

PMID- 7586386
TI  - Collagen gene expression in postangioplasty stenosis.

PMID- 7586389
TI  - Guidelines for the evaluation and management of heart failure. Report of the
      American College of Cardiology/American Heart Association Task Force on Practice
      Guidelines (Committee on Evaluation and Management of Heart Failure).

PMID- 7586388
TI  - Public access defibrillation. A statement for healthcare professionals from the
      American Heart Association Task Force on Automatic External Defibrillation.

PMID- 7586390
TI  - Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Improvement of cardiac ischemia
      at 1 year after PTCA and CABG.
AB  - BACKGROUND: Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise
      treadmill test (ETT) is associated with an increased risk of adverse outcome.
      Myocardial revascularization more often suppresses cardiac ischemia than does
      medical management alone. However, few studies have compared the effects of
      percutaneous transluminal coronary angioplasty (PTCA) with those of coronary
      artery bypass grafting (CABG) on cardiac ischemia and clinical outcome. METHODS
      AND RESULTS: A total of 558 patients were randomly assigned to one of three
      treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study:
      angina-guided medical strategy (n = 184), ischemia-guided medical strategy (n =
      182), or revascularization (n = 192). In patients assigned to revascularization,
      the choice of the procedure, PTCA or CABG, was made by the clinical unit staff
      and patient based on a coronary angiogram usually performed within 2 months of
      enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12
      weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of
      PTCA patients (P = .002). Ischemia on the ETT was no longer present in 46% versus
      23% of the patients, respectively (P = .005). Angina, within 4 weeks of the
      follow-up visit, was absent in 90% versus 68%, respectively (P = .001). These
      clinical variables remained improved in both groups at 1 year. Clinical events
      (myocardial infarction or repeat revascularization) occurred in 1 CABG patient
      versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at
      12 months (P < .001). CONCLUSIONS: Ischemia on the AECG and ETT and angina were
      relieved in many patients after both procedures; however, CABG was superior to
      PTCA, and it was associated with a lower incidence of clinical events at 1 year.
      These results suggest that more complete revascularization relates to better
      clinical outcome. However, a large trial is needed to confirm these results.

PMID- 7586391
TI  - Influence of coronary artery bypass and age on clinical performance after aortic
      and mitral valve replacement with biological and mechanical prostheses.
AB  - The influence of prosthetic type, age, and coronary artery bypass grafting (CABG)
      on valve-related complications by valve position was evaluated in a population of
      2353 bioprosthesis patients (mean age, 66.5 years; range, 13 to 89 years) and in
      a population of 1112 mechanical prosthesis patients (mean age, 59.1 years; range,
      13 to 91 years). The follow-up was complete to 96% and 98%, respectively, for the
      bioprosthesis and mechanical prosthesis groups. The patient groups were evaluated
      by actuarial assessment of survival and valve complications and composites.
      Preoperative factors were evaluated for determination of significant independent
      predictors by multivariate proportional-hazard regression analysis. CABG was an
      influential factor in the actuarial analysis. Survival was superior for aortic
      mechanical replacements without CABG and for mitral replacements, both biological
      and mechanical, without CABG (P < .05). The freedom from thromboembolism (TE) and
      antithromboembolic hemorrhage (ATH) was greater for biological prostheses with
      and without CABG for aortic replacements (P < .05) but not for mitral
      replacements (P = NS). The freedom from valve-related mortality was not
      influenced by CABG for either position (P = NS). The freedom from valve-related
      reoperation was greater for biological prostheses with CABG than without CABG for
      both aortic and mitral replacements (P < .05). The evaluation of covariates as
      independent predictors revealed CABG to be a nonpredictor for aortic valve
      replacement (AVR) (P = NS) but a predictor of survival and valve-related
      reoperation for mitral valve replacement (MVR) (P < .05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7586392
TI  - Determining surgical indications for acute type B dissection based on enlargement
      of aortic diameter during the chronic phase.
AB  - BACKGROUND: In patients with Stanford type B dissection who have been treated
      successfully with medical hypotensive therapy during the acute phase, a large
      number have incurred the risk of surgery during their chronic phases because of
      enlargement of the dissected aorta. The purpose of this study was to determine
      the indications for surgical treatment of acute type B dissection by studying
      chronic-phase enlargements of aortic dissections in patients treated successfully
      with medical hypotensive therapy during the acute phase. METHODS AND RESULTS: In
      41 patients with type B dissection who had been treated medically during the
      acute phase, univariate and multivariate factor analyses were made to determine
      the predominant predictors for chronic-phase enlargement (> or = 60 mm) of the
      dissected aorta. Computed tomography was performed every 4 to 14 months to
      observe whether there was enlargement of the maximum aortic diameter. The
      predominant predictors for aortic enlargement in the chronic phase were the
      existence of a maximum aortic diameter of > or = 40 mm during the acute phase (P
      < .001) and a patent primary entry site in the thoracic aorta (P = .001). The
      values of actuarial freedom from aortic enlargement for the patients with a large
      aortic diameter (> or = 40 mm) during the acute phase and a patent primary entry
      site in the thorax at 1, 3, and 5 years were 70%, 29%, and 22%, respectively. No
      aortic enlargement was observed in the other patients throughout the entire
      follow-up period. CONCLUSIONS: These data suggest that patients with acute type B
      dissection who have a large aortic diameter (> or = 40 mm) and a patent primary
      entry site in the thorax should be treated surgically during the acute phase on
      the condition that the surgical risk in this phase is limited.

PMID- 7586393
TI  - Surgical management of aortic dissection during a 30-year period.
AB  - BACKGROUND: Certain recent studies have demonstrated improved surgical outcome in
      patients with aortic dissection. We analyzed the surgical survival rates of
      patients with acute aortic dissections and the late prognosis of those with
      aortic dissection during a 30-year period. METHODS AND RESULTS: Between 1963 and
      1992, 360 patients (256 men and 104 women; mean +/- 1 SD age, 57 +/- 14 years)
      underwent surgery for aortic dissection: 174 patients had an acute type A (AcA),
      46 an acute type B (AcB), 106 a chronic type A (ChA), and 34 a chronic type B
      (ChB) aortic dissection. The overall operative mortality rate was 24 +/- 8% (26
      +/- 3% for AcA, 39 +/- 8% for AcB, 17 +/- 4% for ChA, and 15 +/- 6% for ChB, [+/-
      70% confidence limit]). The operative mortality rates for patients with acute
      aortic dissection (AcA or AcB) were assessed for five time "windows": 1963 to
      1972 (42 +/- 8%), 1973 to 1977 (37 +/- 8%), 1978 to 1982 (15 +/- 6%), 1983 to
      1987 (27 +/- 6%), and 1988 to 1992 (26 +/- 6%). Logistic regression analysis
      suggested that the low operative mortality rate during the 1978-to-1982 interval
      occurred by chance. Multivariate analysis showed earlier operative year,
      hypertension, cardiac tamponade, renal dysfunction, and older age were
      independent determinants of operative death. Actuarial survival rates (including
      early deaths) after 5, 10, and 15 years for AcA patients were 55%, 37%, and 24%;
      for AcB, 48%, 29%, and 11%; for ChA, 65%, 45%, and 27%; and for ChB, 59%, 45%,
      and 27%. Multivariate analysis revealed that older age and previous operation
      were significant predictors for late death. Freedom from reoperation for all
      patients was 84%, 67%, and 57% at 5, 10, and 15 years, respectively. CONCLUSIONS:
      Although the operative mortality rate decreased over time for patients with
      aortic dissection, the risk for those with acute aortic dissection during the
      last 10 years (1983 to 1992) is probably more realistic than that observed in the
      preceding 5-year interval (1978 to 1982). The operative mortality rates for
      patients with chronic aortic dissection have remained relatively static. Earlier
      diagnosis of acute aortic dissection before development of cardiac tamponade and
      renal impairment is critical to improve the operative salvage rate. Long-term
      outcome still is not optimal, which emphasizes the need for better serial
      postoperative aortic imaging surveillance and medical follow-up and blood
      pressure control.

PMID- 7586394
TI  - Long-term clinical and echocardiographic follow-up after surgical correction of
      hypertrophic obstructive cardiomyopathy with extended myectomy and reconstruction
      of the subvalvular mitral apparatus.
AB  - BACKGROUND: The standard surgical approach to hypertrophic obstructive
      cardiomyopathy (HOCM) was modified in the present series with a combination of
      extended myectomy with partial excision and mobilization of the papillary
      muscles. METHODS AND RESULTS: Between 1979 and 1992, 58 patients (38 men and 20
      women; mean age, 49 +/- 24 years) with HOCM were operated on with the use of this
      different technique. Their intraventricular gradients were 79 +/- 33 (+/- SD) mm
      Hg at rest and increased to 147 +/- 48 mm Hg with provocative maneuvers. Mild-to
      moderate mitral regurgitation was present in 60% of the patients, and severe
      regurgitation was present in 5%. Ten patients required additional aortocoronary
      bypass graft surgery. Follow-up (mean, 84 months) was complete (100%).
      Hemodynamic improvement was documented by a significant (P < .01) decrease in
      left ventricular end-diastolic pressure from 19 +/- 9 to 14 +/- 6 mm Hg and
      reduction of basal outflow tract gradients to 5 +/- 7 mm Hg at rest and 16 +/- 24
      mm Hg after provocation. Late mortality was 1.4% per patient-year, and no sudden
      cardiac deaths occurred during follow-up. Functional status was excellent for 84%
      of the patients; 8 patients were in New York Heart Association functional class
      III, and none were in class IV. Echocardiography revealed no outflow tract
      obstruction. CONCLUSIONS: Extended myectomy and reconstruction of the subvalvular
      mitral apparatus in HOCM result in excellent functional improvement with relief
      of outflow tract obstruction. The technique can be performed safely despite its
      more aggressive surgical nature and allows an individualized strategy depending
      on the patient's extent and distribution of left ventricular hypertrophy.

PMID- 7586395
TI  - Interrupted aortic arch. Impact of subaortic stenosis on management and outcome.
AB  - Interrupted aortic arch (IAA) is often related developmentally to subaortic
      obstruction (SAO). When severe, SAO must be addressed in surgical management of
      IAA. From 1990 to 1993, 25 neonates presented for initial surgical management of
      IAA complexes. Associated lesions were ventricular septal defect (VSD) with or
      without atrial septal defect (19 patients), truncus arteriosus (3 patients),
      tricuspid atresia with transposition of the great arteries (1 patient), aortic
      atresia with VSD (1 patient), and d-transposition of the great arteries with VSD
      (1 patient). Overall hospital mortality was 20% (five deaths). One death was
      related to sepsis and two to sudden hemodynamic decompensation (a 2-kg premature
      infant after arch repair and VSD closure and a neonate with IAA-truncus
      arteriosus after arch repair and truncus repair with aortic root replacement).
      Two deaths were related to low cardiac output in patients with severe subaortic
      narrowing (< 3 mm by two-dimensional echocardiography), which was not addressed
      surgically. Of 10 additional patients judged preoperatively to have severe SAO, 1
      underwent resection of the infundibular septum together with VSD closure and arch
      reconstruction, and 9 underwent a modification of Norwood's operation with arch
      reconstruction and proximal pulmonary artery to aortic anastomosis (7 with
      systemic to pulmonary artery shunts and 2 with right ventricle to pulmonary
      artery outflow tract reconstruction). One patient died 2 months after surgery of
      staphylococcal sepsis. All 9 others were discharged well. Subaortic narrowing is
      a physiologically important element of IAA complexes. When SAO is severe,
      satisfactory initial palliation can be achieved by a modification of Norwood's
      operation.

PMID- 7586396
TI  - Coarctation of the aorta. Repair with polytetrafluoroethylene patch aortoplasty.
AB  - BACKGROUND: The first successful surgical repair of coarctation of the aorta
      (CoAo) was performed in 1944, but during the years that followed a high incidence
      of recoarctation was seen, ranging from 20% to 86%. In response to that problem,
      the patch aortoplasty was introduced in 1957; however, true aneurysms were found
      in the aortic wall opposite the patch after Dacron patch aortoplasty,
      particularly when the coarctation ridge was excised. The purpose of our review
      was to evaluate the results of patch aortoplasty for CoAo using a relatively new
      material, polytetrafluoroethylene (PTFE), and an operative technique that does
      not involve resection of the coarctation ridge. METHODS AND RESULTS: Between 1979
      and 1993, 125 infants and children underwent PTFE patch aortoplasty for CoAo; 111
      of the procedures were primary repairs, and 14 were reoperations. Diagnoses were
      isolated CoAo (96 patients), CoAo and ventricular septal defect (15 patients),
      and CoAo with complex intracardiac anomaly (14 patients). Patient age at the time
      of repair ranged from 4 days to 17 years (mean age, 5.1 +/- 4.5 years). There
      were no instances of intraoperative mortality or paraplegia. There were 4 deaths
      from 10 to 40 days postoperatively, all in neonates (mean age, 33 days) who
      received additional intracardiac procedures for complex associated anomalies.
      Follow-up has ranged from 6 months to 12.5 years (mean, 4.5 +/- 3.2 years). All
      children had postoperative chest roentgenograms, 80 (66%) patients have had a
      postoperative echocardiogram and 16 (13%) a cardiac catheterization. One patient
      had successful repair of a false aneurysm 4 months postoperatively. No patient
      has developed a late true aneurysm. Of the patients < 1 month of age at the time
      of CoAo repair (12 patients), 6 patients had recurrent CoAo (gradient > 20 mm Hg)
      compared with only 4 recurrences in 97 patients > 1 month of age at the time of
      repair (P < .001). CONCLUSIONS: For children > 1 year of age, PTFE patch
      aortoplasty remains our procedure of choice for CoAo repair because of the low
      mortality rate, low recoarctation rate, and absence of late true aneurysms. We
      have stopped using this technique for infants < 1 month of age because of the
      high recurrence rate.

PMID- 7586397
TI  - Long-term outcome of cardiac surgery in patients with mitral stenosis and severe
      pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension increases perioperative risk in patients
      having mitral valve replacement, but most studies have included patients with
      mixed mitral valve disease and have not examined long-term outcome. METHODS AND
      RESULTS: We retrospectively examined the results and predictors of outcome of
      cardiac surgery in 43 patients (age, 62 +/- 13 years [mean +/- SD]; 81% women)
      with a primary diagnosis of mitral stenosis and severe pulmonary hypertension
      (pulmonary artery systolic pressure > or = 60 mm Hg or mean pressure > or = 50 mm
      Hg). Patients with more than mild mitral regurgitation were excluded. Thirty
      eight patients (88%) were in NYHA functional class III or IV, and 11 patients
      (26%) had an acute presentation requiring urgent surgery. Preoperative
      hemodynamics demonstrated a mean mitral valve area of 0.7 +/- 0.3 cm2, mean
      pulmonary artery pressure of 50 +/- 9 mm Hg, and pulmonary artery systolic
      pressure of 81 +/- 18 mm Hg. Other characteristics included right ventricular
      failure (18 patients), coronary artery disease (16 patients), and critical aortic
      stenosis (11 patients). Forty patients underwent mitral valve replacement with St
      Jude prostheses; 3 had open commissurotomy. Additional surgical procedures
      included aortic valve replacement (42%), coronary artery bypass graft surgery
      (26%), and tricuspid valvuloplasty (16%). There were 5 perioperative deaths
      (11.6%), and 7 other patients (16%) had major complications, including
      reoperation for hemorrhage, stroke, respiratory failure, myocardial infarction,
      or a > 30-day hospitalization. Univariate analysis of demographic, hemodynamic,
      and operative characteristics identified the following predictors of
      perioperative death (P < .05): acute presentation, clinical evidence of right
      ventricular failure, impaired left ventricular ejection fraction, and increased
      left ventricular diastolic pressure. Predictors of complications (P < .05) were
      acute presentation, ECG evidence of right ventricular hypertrophy, and elevated
      right ventricular systolic pressure. Multivariate analysis showed only acute
      presentation and right ventricular hypertrophy as predictors of perioperative
      death or major complications, respectively. Five- and 10-year actuarial survivals
      were 80% and 64%, respectively. The only predictor of long-term mortality was
      advanced age. Functional NYHA status was improved by one grade or more in 76% of
      survivors. CONCLUSIONS: Patients referred to a tertiary care hospital in the
      United States with mitral stenosis and severe pulmonary hypertension often have
      other associated cardiac diseases and comorbid conditions. Cardiac surgery can be
      successfully performed with an acceptable mortality, and risk factors for poor
      perioperative outcome can be identified by preoperative clinical characteristics.
      Younger patients have the best long-term survival, and most survivors experienced
      long-term improvement in functional status.

PMID- 7586399
TI  - Determinants of early mortality and late survival in mitral valve endocarditis.
AB  - BACKGROUND: Infective mitral valve endocarditis continues to be a significant
      surgical challenge. The objective of this study was to examine our experience
      with mitral valve endocarditis surgery and identify determinants of early
      mortality and late survival. METHODS AND RESULTS: Over a 24-year period, mitral
      valve surgery was performed in 96 patients for infective mitral valve
      endocarditis. Patient age ranged from 20 to 78 years (median age, 52 years).
      There were 44 women (46%), and 48 of the 96 patients (50%) were in New York Heart
      Association functional class IV before surgery. Native valve endocarditis (NVE)
      and prosthetic valve endocarditis (PVE) were present in 72 patients (75%) and 24
      patients (25%), respectively. Surgery during the active phase of endocarditis
      (AE) was required in 60 patients (62%) and during the healed phase (HE) in 36
      (38%). The main indications for surgery in the AE group were congestive heart
      failure (60%), active sepsis (67%), peripheral emboli (47%), and acute renal
      failure (20%), and for the HE group the main indication was progressive
      congestive heart failure (69%). The overall operative mortality was 5.2%.
      Multivariate logistic regression analysis identified PVE (odds ratio [OR] 22.5;
      +/- 95% confidence interval, CI, 1.9 to 268; P = .014) and an associated
      procedure (OR 13.3; +/- 95% CI, 1.5 to 120; P = .021) to be independent
      predictors for early mortality. Follow-up was 97% complete, with a median of 3.5
      years. Overall 5- and 10-year survivals were 83 +/- 4% and 63 +/- 8%,
      respectively. Multivariate analysis for late mortality identified PVE to be a
      significant predictor of late mortality (hazards ratio = 3.1, +/- 95% CI, 1.4 to
      6.8, P = .006). There were no significant differences in long-term morbidity
      results among the various subsets of mitral valve endocarditis. CONCLUSIONS:
      Mitral valve surgery for infective endocarditis is a significant high-risk
      procedure for PVE and when combined with associated procedures. The activity of
      endocarditis does not appear to have any influence on early mortality or long
      term survival.

PMID- 7586398
TI  - Late outcome after coronary artery bypass graft surgery in patients < 40 years
      old.
AB  - BACKGROUND: Randomized trials confirm the long-term efficacy of coronary artery
      bypass graft surgery (CABG), although there are no randomized data in patients <
      40 years old. Because these patients have been reported to have an early
      recurrence of symptoms, the long-term postoperative outcome was examined. METHODS
      AND RESULTS: The long-term outcome of patients (n = 221) < 40 years old
      undergoing CABG at Green Lane Hospital, New Zealand, from 1970 to 1992 was
      determined. The 30-day mortality rate was 1.8% for initial and 9.5% for redo
      CABG. The median times to angina or myocardial infarction (recurrent ischemic
      event), further intervention, and death were 6.0, 9.6, and 14.2 years,
      respectively. Factors associated with increased late mortality on univariate
      analysis included end-systolic volume (ESV) > or = 80 mL (P = .004; 10-year
      mortality 19% versus 39% ESV > or = 80 mL), no internal mammary conduit (P =
      .01), no lipid-modifying therapy (P = .005), and no postoperative aspirin use (P
      = .0002); the latter was also associated with increased recurrent ischemic events
      (P = .04) or increased reintervention (P = .02). On stepwise logistic regression
      analysis, factors associated with increased late mortality were increasing ESV (P
      = .004), no internal mammary artery conduit (P = .009), diabetes (P = .04), and
      no postoperative aspirin (P = .02); the latter was also associated with increased
      recurrent ischemic events (P = .02). Hypercholesterolemia (> or = 6.5 mmol/L) was
      present in 65% of patients at presentation and 45% at follow-up. CONCLUSIONS: To
      attempt to prevent recurrent ischemia or late death, patients < 40 years old who
      require CABG should receive internal mammary conduits, aspirin, lipid-modifying
      therapy, therapy to inhibit ventricular dilatation, and strict diabetes
      management.

PMID- 7586400
TI  - Early results of a simplified method of mitral valve annuloplasty.
AB  - BACKGROUND: We hypothesized that a simple, unmeasured posterior annuloplasty
      technique (two thirds of a 27-mm Duran ring) offered advantages of
      standardization and ease of insertion. METHODS AND RESULTS: A consecutive series
      of all patients (n = 418; median age, 67 years) having mitral valve repair
      performed by two surgeons was analyzed to determine the outcome of three
      different annuloplasty techniques: commissural annuloplasty (n = 124), complete
      ring annuloplasty (n = 113), and an unmeasured, posterior, partial ring
      annuloplasty (n = 181). Intraoperatively, before repair, severity of mitral
      regurgitation as measured by double sampling dye curves and transesophageal
      echocardiography was similar in all three groups; after mitral valve repair,
      intraoperative assessment showed a similar degree of reduction in regurgitation
      in the three annuloplasty groups. Before hospital dismissal, transthoracic
      echocardiography demonstrated that the mean mitral valve areas and gradients were
      similar in the three groups; more patients having commissural annuloplasty were
      classified as having grade II or greater regurgitation. Mortality (n = 7, 1.7%)
      and need for reoperation (n = 8, 1.9%) was low in all groups despite the fact
      that additional procedures were performed in 48.8% of patients. Durations of
      cardiopulmonary bypass and aortic cross-clamping were significantly less in
      patients having commissural or posterior annuloplasties compared with those
      receiving a complete ring annuloplasty. CONCLUSIONS: These early results indicate
      that the posterior annuloplasty method is reproducible and expeditious.
      Postoperative valve function as assessed by degree of regurgitation,
      transvalvular gradient, and valve area was similar to that obtained by measured,
      complete ring annuloplasty and superior to that found in patients having
      commissural annuloplasty.

PMID- 7586401
TI  - Early changes in regional and global left ventricular function after aortic valve
      replacement. Comparison of crystalloid, cold blood, and warm blood cardioplegias.
AB  - BACKGROUND: The clinical effects of different cardioplegic methods on left
      ventricular (LV) function have not been fully elucidated, particularly in the
      setting of myocardial hypertrophy. METHODS AND RESULTS: Sixty-four patients (mean
      age, 62 +/- 12 years; 41 men, 23 women) who were undergoing elective aortic valve
      replacement (stenosis, 49; regurgitation, 15; concomitant coronary artery bypass
      grafting, 22), with LV mass index 230 +/- 70 g/m2, were randomized to the
      following groups: antegrade crystalloid cardioplegia (CCP, 21 patients),
      antegrade/retrograde cold blood cardioplegia (CBP, 23 patients), or continuous
      retrograde warm (37 degrees C) blood cardioplegia (WBP, 20 patients). Mean aortic
      cross-clamp and cardiopulmonary bypass times were 100 +/- 20 and 126 +/- 24
      minutes. Positive inotropic drug therapy was required postoperatively in 9
      patients after CBP, 14 after CCP, and 18 after WBP. Perioperative LV function was
      assessed using transesophageal M-mode echocardiography, combined with high
      fidelity LV pressure recording and thermodilution cardiac output, before bypass
      and 0.5, 1, 3, 6, 12, and 20 hours after cross-clamp removal. There was a similar
      fall in LV peak circumferential wall stress at constant LV end-diastolic
      dimension in each group after aortic valve replacement. The increase in
      contraction velocity was significant from 0.5 hour with CBP; however, no
      significant increase occurred until 12 hours with CCP and until 20 hours with
      WBP. The rate and extent of LV pressure fall and early diastolic filling rate
      both increased with CBP, and only in this group did ventricular coordination
      improve. LV stroke work index was maintained with CBP throughout the
      postoperative period with less inotropic support than with the other two methods.
      CONCLUSIONS: In the hypertrophied LV, CBP offers the best preservation of
      myocardial physiological response and ventricular function with less inotropic
      support.

PMID- 7586402
TI  - Early and late mortality of patients undergoing aortic valve replacement after
      previous coronary artery bypass graft surgery.
AB  - BACKGROUND: In a small number of patients who undergo coronary artery bypass
      graft surgery (CABG), a hemodynamically significant aortic valve lesion requiring
      aortic valve replacement (AVR) develops as they grow older. In a limited number
      of studies in small patient groups, high mortality has been shown in patients
      undergoing AVR after CABG. We undertook this study to determine the mortality
      risk factors for patients who undergo AVR after CABG procedures. METHODS AND
      RESULTS: The outcome of 104 patients treated at our institution between January
      1983 and December 1993 was retrospectively reviewed. The initial surgery was CABG
      in all patients. The patient population included 86 men (83%) and 18 women (17%);
      their mean age was 67 years. Overall, 70% of patients had congestive heart
      failure, and 96% had multivessel coronary artery disease. The diagnosis was
      aortic stenosis in 68% of patients, aortic insufficiency in 16%, and combined
      aortic stenosis and aortic insufficiency in 16%. Postoperative complications
      included worsening congestive heart failure (35%), perioperative myocardial
      infarction (13%), and bleeding (28%). The early mortality was 14%, and the late
      mortality was 17% (mean follow-up, 35 months). The risk factors for early
      mortality were number of diseased vessels (P = .028), renal failure (0.000), and
      prior myocardial infarction (P = .028). A perioperative predictor of early
      mortality was cardiopulmonary bypass time (P = .000). The risk factors for late
      mortality included preoperative diabetes mellitus (P = .007), postoperative acute
      respiratory distress syndrome (P = .011), and ventricular arrhythmias (P =
      .0001). The survival at 1, 5, and 10 years was 96%, 75%, and 49%, respectively.
      CONCLUSIONS: Risk factors were identified for early and late mortality in
      patients undergoing AVR after previous CABG. Although early morbidity and
      mortality were high, the longterm outcome of the survivors was favorable.

PMID- 7586403
TI  - Screening scale predicts patients successfully receiving long-term implantable
      left ventricular assist devices.
AB  - BACKGROUND: Although use of long-term implantable left ventricular assist devices
      (LVAD) is becoming more popular, further reduction of the mortality rate
      accompanying device insertion through improved patient selection would make this
      alternative even more appealing. We sought to develop a scoring system that was
      based on criteria obtainable at the time of evaluation and predictive of
      successful early outcome and simple to apply. METHODS AND RESULTS: Patients (n =
      56) undergoing LVAD insertion between 1990 and 1994 were screened for easily
      obtainable preoperative risk factors. To test the association between survival
      and each risk factor, a chi 2 analysis was performed, and relative risks were
      estimated. Oliguria, ventilator dependence, elevated central venous pressure,
      elevated prothrombin time, and reoperation stats had low probability values and
      high estimated relative risks. On the basis of these relations, a risk factor
      selection scale (RFSS) (range, 0 to 10) was developed by computing appropriate
      weights for each risk factor. The distribution of patients for each scale score
      reveal that with RFSS > or = 5, most device recipients will die (P < .001). The
      average RFSS (+/- SD) of survivors (n = 42) was 2.45 +/- 1.73 compared with 5.43
      +/- 2.85 in nonsurvivors (n = 14) (P < .0001). Univariate logistical regression
      was also significant (score statistic, 16.2; df = 1; P = .001). CONCLUSIONS: The
      RFSS is simple, easy to apply, and statistically valid. Physicians could use the
      scale as a starting point in discussing the suitability for LVAD implantation in
      a specific patient and as a basis for comparing patient outcomes.

PMID- 7586404
TI  - Target heart failure populations for newer therapies.
AB  - BACKGROUND: The scarcity of donor hearts has created a large population of heart
      failure patients who are unlikely to undergo transplantation. Newer surgical
      therapies that might sustain such patients at home previously have been applied
      in critical situations in which early outcome is jeopardized by multiorgan
      failure. The optimal population for studies of extended support would be
      ambulatory patients with low operative risk but high risk of later unfavorable
      outcome. METHODS AND RESULTS: Baseline clinical, echocardiographic, and
      hemodynamic data were collected prospectively between 1988 and 1993 in 500
      patients who were discharged on tailored medical therapy after evaluation for
      transplantation. Specific criteria were examined to identify high risk of death
      or need for urgent transplantation during the next 2 years. In 265 patients with
      ejection fraction < or = 25% and initial New York Heart Association class IV
      symptoms, survival at 2 years was 55% (without urgent transplantation, 45%).
      Lower cardiac index or higher filling pressures at the time of referral did not
      confer higher risk, which was predicted by persistence of higher pressures after
      therapy. Serum sodium below 133 was associated with 34% 2-year survival without
      urgent transplantation, and ventricular dimension > 80 mm with a rate of 25%.
      Patients with initial peak oxygen consumption > 10 mL/kg per minute had a 2-year
      event-free rate of 72% compared with 48% for those with < 10 mL/kg per minute and
      32% for those unable to exercise at referral. Demonstration of a 30% decrease in
      mortality with a controlled trial of new therapy in patients with ejection
      fraction < or = 25% would require 600 patients with class III symptoms or almost
      300 patients with class IV symptoms unless another criterion were added.
      CONCLUSIONS: Ambulatory populations with high predicted event rates can be
      identified at initial evaluation, when hemodynamic criteria may be less useful
      than ventricular dimension, serum sodium, and ability to exercise. The use of
      outcome data from previous eras may lead to overestimation of benefits from newer
      therapies and underestimation of the sample size required in a prospective
      trials.

PMID- 7586405
TI  - Influence of intimal thickening on coronary blood flow responses in orthotopic
      heart transplant recipients. A combined intravascular Doppler and ultrasound
      imaging study.
AB  - BACKGROUND: Intravascular ultrasound imaging detects epicardial intimal
      thickening in the majority of heart transplant recipients with angiographically
      normal epicardial coronary arteries. Although coronary artery vasoreactivity is
      abnormal after cardiac transplantation, intimal thickening does not appear to
      affect conduit vessel responses. However, the effect of intimal thickening on
      both conduit and resistance vessel responses, as measured by changes in
      volumetric coronary blood flow (CBF), is unknown. METHODS AND RESULTS: Epicardial
      coronary artery conductance and microvascular resistance vessel responses were
      studied after intracoronary adenosine and nitroglycerin administration in 36
      orthotopic heart transplant recipients 1 month to 7 years after transplantation.
      Sequentially measured coronary flow average peak velocity ([APV, cm/s] 0.018 in
      Doppler guide wire) and epicardial luminal cross-sectional area ([CSA, mm2] 4.3F
      30-MHz ultrasound catheter) data were obtained at baseline and during peak
      hyperemia after administration of 12 to 18 micrograms IC adenosine and 150 to 200
      micrograms IC nitroglycerin. Volumetric CBF (mL/min) was calculated as CBF = APV
      (cm/s) x CSA (mm2) x 60 seconds/1 min x 1 cm2/100 mm2 x 0.5. Measurements were
      made from a discrete position in the proximal left anterior descending (LAD)
      artery (n = 22), mid-LAD artery (n = 7), proximal circumflex artery (n = 6), and
      proximal right coronary artery (n = 1). Intimal thickening was present in 19 of
      32 patients (60%). Both adenosine and nitroglycerin increased APV (from 18.9 +/-
      4.9 to 56.0 +/- 11.5 cm/s for adenosine and from 20.2 +/- 5.3 to 49.1 +/- 11.5
      cm/s for nitroglycerin; both P < .05). Coronary flow velocity reserve was
      significantly higher for adenosine compared with nitroglycerin (3.1 +/- 0.6
      versus 2.5 +/- 0.7, respectively; P < .001). Epicardial luminal CSA was unchanged
      during adenosine hyperemia compared with baseline (17.4 +/- 3.8 versus 17.3 +/-
      4.0 mm2, respectively; P = NS) but was significantly greater during nitroglycerin
      hyperemia compared with baseline (18.7 +/- 3.8 versus 17.3 +/- 4.0 mm2, 6.2 +/-
      3.6% change; P < .05). Baseline CBF was similar before drug administration.
      Hyperemic adenosine and nitroglycerin CBF responses (297 +/- 99 and 276 +/- 87
      mL/min, respectively; P = NS) and CBF reserve (3.0 +/- 0.7 and 2.7 +/- 0.7,
      respectively; P = NS) were not significantly different. Importantly, intimal
      thickening did not diminish resting or hyperemic APV, coronary flow velocity
      reserve, luminal CSA, CBF, or CBF reserve responses. CONCLUSIONS: In this study
      of angiographically normal heart transplant recipients, epicardial intimal
      thickening does not diminish conduit and resistance vessel responses during
      endothelial-independent vasodilator administration.

PMID- 7586406
TI  - Effect of the implantable left ventricular assist device on neuroendocrine
      activation in heart failure.
AB  - BACKGROUND: The HeartMate left ventricular assist device has been successfully
      used as a bridge to cardiac transplantation. Because many patients exhibit marked
      clinical improvement in their heart failure after HeartMate implantation, we
      studied the physiological effect of this device on the neurohormonal axis.
      METHODS AND RESULTS: In 13 patients awaiting transplant (mean cardiac index, 1.7
      +/- 0.3 L.min-1.m-2) who underwent HeartMate implantation, venous atrial
      natriuretic peptide, epinephrine, norepinephrine, plasma renin activity,
      angiotensin, and arginine vasopressin were measured immediately before insertion
      and at explant/transplantation. Mean time to explant was 86 +/- 40 days. All
      patients were taken off inotropic medications within 1 month. Mean cardiac index
      on support before explant was 3.1 +/- 0.9 L.min-1.m-2. Plasma renin activity
      decreased from 57 +/- 56 ng.mL-1.h-1 at baseline (before insertion) to 3 +/- 3
      ng.mL-1.h-1 at explant (mean percent change, 92%; P < .001). Angiotensin II level
      decreased from 237 +/- 398 U/L at baseline to 14 +/- 14 U/L at explant (mean
      percent change, 73%; P < .001). Plasma epinephrine level fell from 6800 +/- 1323
      pg/mL at baseline to 46 +/- 46 pg/mL at explant (mean percent change, 86%; P <
      .001). Norepinephrine level decreased from 2953 +/- 1457 pg/mL at baseline to 518
      +/- 290 pg/mL at explant (mean percent change, 79%; P < .001). Atrial natriuretic
      peptide fell from baseline values of 227 +/- 196 to 168 +/- 40 pg/mL at explant
      (mean percent change, -49%; P = 519); and arginine vasopressin level decreased
      from 6 +/- 6 pg/mL at baseline to 0.8 +/- 0.5 pg/mL (mean percent change, 69%; P
      = .002). CONCLUSIONS: We provide data supporting that the neurohormonal axis
      markedly improves after HeartMate implantation, providing biochemical
      confirmation of the improvement in hemodynamic status.

PMID- 7586408
TI  - Determinants of length of stay after coronary artery bypass graft surgery.
AB  - BACKGROUND: Rising healthcare costs have prompted limitations in the length of
      stay (LOS) for patients undergoing coronary artery bypass graft surgery (CABG).
      Because not all patients are candidates for early discharge, in the present study
      our aim was to determine factors that prolong LOS. METHODS AND RESULTS: In 194
      consecutive patients undergoing CABG procedures, LOS was > 7 days in 37%.
      Stepwise multiple regression procedures and chi 2 testing were used to determine
      what factors prolonged LOS for > 7 days. Preoperative factors that significantly
      (P < .05) prolonged LOS included repeat CABG, CABG plus valve surgery, congestive
      heart failure, preoperative coronary care unit stay, renal failure, and insulin
      dependent diabetes mellitus. Patients with at least one risk factor had a
      significantly higher incidence of LOS of > 7 days (47% versus 17%; P < .001).
      Significant (P < .05) postoperative factors prolonging LOS included arrhythmias,
      respiratory insufficiency, pneumonia, and wound infection. Of patients with at
      least one risk factor, 83% had LOS of > 7 days (P < .001). CONCLUSIONS: The
      presence of certain preoperative and post-operative risk factors can be predicted
      to prolong LOS after CABG surgery. This should be taken into consideration when
      defining reimbursement policies.

PMID- 7586407
TI  - Standard orthotopic heart transplantation versus total orthotopic heart
      transplantation. A transesophageal echocardiography study of the incidence of
      left atrial thrombosis.
AB  - BACKGROUND: After standard orthotopic heart transplantation (Sd HT), the enlarged
      resultant atria may promote atrial thrombosis. The purpose of this study was to
      compare the incidence of spontaneous echo contrast and left atrial thrombosis
      after Sd HT and total orthotopic (Tot HT) heart transplantation. METHODS AND
      RESULTS: Transesophageal echocardiography (TEE) was performed in 75 patients with
      Sd HT and in 20 patients with Tot HT. Despite the use of antiplatelet therapy, an
      acute arterial embolism occurred in 11 (15%) of the 75 patients with Sd HT but in
      none of the 20 Tot HT patients. All patients were in sinus rhythm. Left
      ventricular ejection fraction was similar in Sd HT and Tot HT patients. Left
      atrial diameter was smaller in Tot HT patients than in Sd HT patients (41 +/- 4
      versus 58 +/- 6 mm, P < .001). In Sd HT patients, spontaneous echo contrast was
      present in 43 patients (57%) and was associated with left atrial thrombus in 20
      patients (on the left atrial appendage in 12 patients, on the posterior wall in
      6, and on the suture in 2). No thrombus was detected by transthoracic
      echocardiography; all thrombi were detected by TEE. On the other hand, no left
      atrial thrombus was observed in Tot HT patients, and only 1 patient had
      spontaneous echo contrast. Of the 11 Sd HT patients who experienced an arterial
      embolism, 5 had both spontaneous echo contrast and left atrial thrombus and 5 had
      only spontaneous echo contrast. CONCLUSIONS: This study demonstrates a high rate
      of left atrial thrombus after Sd HT and emphasizes the role of TEE in the follow
      up of these patients. The therapeutic implications are the need for a preventive
      anticoagulant therapy in the high-risk population receiving Sd HT diagnosed with
      TEE and the consideration of Tot HT as a better surgical approach as far as
      thrombotic complications are concerned.

PMID- 7586409
TI  - Generation of tumor-specific T lymphocytes for the treatment of posttransplant
      lymphoma.
AB  - BACKGROUND: The incidence of lymphoproliferative disease, including B-cell
      lymphomas (BCL) in patients who have undergone heart or combined heart-lung
      transplants, has been reported to be as high as 15%. The majority of these tumors
      contain Epstein-Barr virus (EBV) DNA and regress when immunosuppressive agents
      are discontinued. This tumor regression is thought to be secondary to cytotoxic T
      lymphocytes (CTL) reactive to EBV-infected cells whose function is impaired in
      patients receiving immunosuppressive agents. We hypothesize that EBV-CTL expanded
      in the absence of these agents may demonstrate an antitumor effect against an EBV
      expressing human BCL in vitro and in vivo. METHODS AND RESULTS: An EBV-expressing
      BCL from a heart transplant recipient was isolated and expanded in culture. EBV
      CTL were generated by stimulation of peripheral blood leukocytes with irradiated
      autologous tumor cells in low-dose interleukin-2. Autologous BCL, HLA-mismatched
      BCL, lymphokine-activated killer target cell line (Daudi), and the natural killer
      target cell line (K562) were used in a standard 4-hour cytotoxicity assay using
      51CrO4 after 7, 14, and 28 days of stimulation. There was significant percent
      specific lysis of autologous BCL targets (78%) at an effector-to-target ratio as
      low as 20:1 as compared with control cells. EBV-CTL were then adoptively
      transferred into SCID mice (provided by Duke University Vivarium) that had been
      engrafted with autologous BCL 7 days before. There was a significant survival
      advantage to those mice engrafted with EBV-CTL as compared with control cells.
      CONCLUSIONS: The results indicate that ex vivo expansion of EBV-CTL in the
      absence of immunosuppressive agents results in a population that has significant
      antitumor activity. This strategy may be useful in the generation of EBV-CTL that
      might be effective antitumor agents in transplant recipients with EBV-associated
      lymphomas.

PMID- 7586410
TI  - Pretransplant risk factors and causes of death or graft loss after heart
      transplantation during early infancy. Pediatric Heart Transplant Team, Loma
      Linda.
AB  - BACKGROUND: This study was performed to report causes of death or graft loss and
      to identify possible pretransplant risk factors for death or graft loss in
      infants after heart transplantation. METHODS AND RESULTS: Pretransplant risk
      factors were compared for 153 infants registered for heart transplantation within
      90 days of life and transplanted from November 1985 to June 1994. Factors
      assessed were diagnosis, age at transplantation, race, weight, blood type, sex,
      donor/recipient blood type match, sex match, weight ratio, fetal registration,
      locale of pretransplant waiting period, mechanical ventilation, ischemic time,
      and the need for atrial septostomy or septectomy pretransplantation. No factor
      was associated with death or graft loss at 1 month or 1 year. Causes of death or
      graft loss were determined using clinical course and pathology data when
      available. Death or grafts lost at 1 month, 1 year, and > 1 year were 14, 13, and
      15, respectively. Causes of death or graft loss expressed as a percent (at 1
      month, 1 year, and > 1 year, respectively) were acute rejection (14, 23, 27),
      chronic rejection and posttransplant coronary disease (0, 8, 47), infectious
      causes (21, 15, 13), early graft failure (21, 0, 0), technical issues (21, 23,
      0), chronic graft dysfunction (0, 15, 0), and miscellaneous (21, 15, 13). The
      graft loss rate at 1 year was significantly correlated (linear regression, r2 =
      .66; P < .05) with the year of transplantation. Actuarial survival in this
      population was 91% at 1 month, 81% at 1 year, and 73% at 3 years. CONCLUSIONS:
      Heart transplantation in the young infant can be performed with acceptable short
      term and midterm results. Causes of death or graft loss and survival are similar
      to adult data. No pretransplant risk factors were identified. The experience
      level of the transplant team members affects survival. The diagnosis and
      management of rejection remain a major challenge.

PMID- 7586411
TI  - Clinical study of the effects of latissimus dorsi muscle flap stimulation after
      cardiomyoplasty.
AB  - BACKGROUND: Beneficial hemodynamic effects after dynamic cardiomyoplasty have
      been inconsistently demonstrated, and the effects seen may be due to the wrap
      itself, to flap stimulation, or both. The aim of this study was to determine
      whether flap stimulation per se acts as a systolic active process after
      cardiomyoplasty. METHODS AND RESULTS: Catheterizations were performed in 13
      patients 14.4 +/- 7 months after cardiomyoplasty. New York Heart Association
      functional class decreased from 3.3 to 2.1 after the procedure (P = .0005).
      Hemodynamic evaluations were first performed with the stimulator on in the 2:1
      mode and then after the stimulator had been off for at least 24 hours. Left
      ventricular (LV) ejection fraction increased from 25.1 +/- 6% before surgery to
      28.2 +/- 6.7% with the stimulator on after cardiomyoplasty (P = .04). When
      stimulation was stopped, there was no change (P > .05) in indexes of systolic or
      diastolic LV function (peak systolic LV pressure, LV ejection fraction, peak
      positive dP/dt, peak negative dP/dt, or tau). Pulmonary capillary wedge pressure
      and cardiac index were unchanged when stimulated and nonstimulated settings were
      compared (P > .05). However, a remarkable heterogeneity of individual responses
      was observed. Ejection fraction and cardiac index decreased with the stimulator
      off in 3 patients, but peak positive dP/dt decreased in 6 patients; diastolic
      function deteriorated in 2 patients, but a slight improvement was noted in 3
      patients. Cardiothoracic ratio, echocardiographic LV end-diastolic dimension, and
      fractional shortening remained unchanged between immediate (< 1 month) and long
      term (36.7 +/- 25.9 months) postoperative evaluations. CONCLUSIONS: In the
      majority of our patients, there was no short-term hemodynamic benefit of flap
      stimulation; therefore, we conclude that the efficacy of cardiomyoplasty may be a
      consequence of a passive "girdling effect," which limits the progression of
      ventricular enlargement and further deterioration of ejection fraction.

PMID- 7586412
TI  - Peak oxygen consumption and resting left ventricular ejection fraction changes
      after cardiomyoplasty at 6-month follow-up.
AB  - BACKGROUND: The effects of cardiomyoplasty on cardiopulmonary exercise test
      characteristics are not fully known. METHODS AND RESULTS: We determined in 19
      patients who underwent cardiomyoplasty for treatment of refractory heart failure
      (New York Heart Association [NYHA] functional class III) before (pre) and at 6
      month follow-up (post) maximum oxygen consumption (peak VO2), NYHA functional
      class, and resting left ventricular ejection fraction (LVEF) (MUGA). We analyzed
      the results according to pre peak VO2 < or > 14 mL/kg per minute and the
      correlation between the changes in absolute values of LVEF and peak VO2. Pre- and
      post-peak VO2 values were 15.9 +/- 4.4 and 18.6 +/- 6.4 mL/kg per minute,
      respectively (P = .059). In the subgroup with pre-peak VO2 < 14 mL/kg per minute,
      the peak VO2 increased from 11.1 +/- 1.9 to 16.4 +/- 6.2 mL/kg per minute (P =
      .02). The subgroup with peak VO2 > 14 mL/kg per minute showed pre- and post-peak
      VO2 of 19.2 +/- 2.6 and of 20.1 +/- 7 mL/kg per minute, respectively (P = .06).
      The pre-total exercise time of the entire group increased from 688.4 +/- 222.1 to
      833.7 +/- 241.6 seconds (P < .04). For the subgroup with preoperative peak VO2 <
      14 mL/kg per minute, exercise time improved from 585 +/- 76.9 to 825 +/- 186.3
      seconds (P < .01). In the subgroup with preoperative VO2 > 14 mL/kg per minute,
      the preexercise and postexercise time was 763.6 +/- 264.4 and 840 +/- 282
      seconds, respectively (P = .4). Pre-LVEF increased from 20.6 +/- 3.3% to 24.2 +/-
      7.8% at 6 months of follow-up (P = .02). At 6 months of follow-up, 9 patients
      were in NYHA functional class I and 10 were in class II. There was no correlation
      between LVEF values and absolute values of peak VO2 before (r = .123, P = .6) and
      after (r = .27, P = .2) cardiomyoplasty. A weak correlation was observed between
      the changes in absolute values of peak VO2 and LVEF from the preoperative to the
      postoperative period (r = .48, P = .048). CONCLUSIONS: Cardiomyoplasty is a
      useful method for improving NYHA functional class and LVEF in patients with heart
      failure. Peak VO2 < 14 mL/kg per minute before cardiomyoplasty may be a selection
      criterion with which to determine improved exercise capacity after surgery. The
      effects of cardiomyoplasty on LVEF appear to be partially associated with maximum
      exercise capacity changes.

PMID- 7586414
TI  - Use of the bidirectional Glenn procedure in the presence of forward flow from the
      ventricles to the pulmonary arteries.
AB  - BACKGROUND: Relative regression of the pulmonary arterial size has been reported
      after a conventional bidirectional Glenn procedure. Maintaining a supplemental
      pulmonary flow could be of surgical value unless the option also militates
      against the efficacy of the partial right heart bypass. METHODS AND RESULTS:
      Twenty-seven patients considered unsuitable for a Fontan-type procedure underwent
      a bidirectional Glenn procedure in the presence of forward flow from the
      ventricles to the pulmonary arteries, the flow being maintained through the
      pulmonary trunk in 22 or a systemic-to-pulmonary shunt in 5. There was one
      surgical death due to atrioventricular valvular regurgitation. Subsequently, 9
      patients have successfully undergone a total cavopulmonary connection 2.6 +/- 1.9
      years after the initial procedure. Preoperative and postoperative
      catheterizations revealed changes in arterial oxygen saturation (75 +/- 11%
      compared with 83 +/- 7%, P < .001) and end-diastolic volumes of the systemic
      ventricles (from 238 +/- 92% to 188 +/- 97% of the expected normal volume, P <
      .01), whereas no difference was detected in the mean cross-sectional area of the
      right and left pulmonary arteries compared with the expected normal value for the
      right pulmonary artery (from 76 +/- 21% to 81 +/- 20%) or in the ventricular
      ejection fraction (from 53 +/- 8% to 50 +/- 14%). The relative regression or
      growth of the pulmonary arterial size was statistically related to the size of
      the channel for forward flow. CONCLUSIONS: Maintenance of forward flow from the
      ventricle provides a feasible means, when performing a bidirectional Glenn
      procedure, of protecting against regression of pulmonary arterial size as well as
      off-loading the ventricles and improving arterial oxygen saturation.

PMID- 7586416
TI  - Does an additional source of pulmonary blood flow alter outcome after a
      bidirectional cavopulmonary shunt?
AB  - BACKGROUND: The bidirectional cavopulmonary shunt has become an important
      intermediate step in the treatment of pediatric patients with single ventricle
      physiology who are ultimately destined for palliative surgery. We wanted to know
      whether there would be risks or benefits if an additional source of pulmonary
      blood flow was left after a bidirectional cavopulmonary shunt. METHODS AND
      RESULTS: We retrospectively reviewed the medical and surgical records of all
      patients who underwent a bidirectional cavopulmonary shunt at the Children's
      Hospital of Wisconsin between January 1991 and December 1993. A total of 43
      patients were identified. Anatomic diagnoses included double inlet left ventricle
      (14 patients), tricuspid atresia (8 patients), pulmonary atresia with intact
      septum (6 patients), single right ventricle (5 patients), hypoplastic left heart
      (3 patients), unbalanced atrioventricular septal defect (3 patients), and other
      complex lesions (4 patients). We then divided the patients into two groups for
      purposes of analysis. Group 1 had only the cavopulmonary shunt as a source of
      pulmonary flow (22 patients); group 2 had an additional source of pulmonary flow
      (21 patients). Patient age at the time of cavopulmonary shunt ranged from 6
      months to 12 years, with group 1 patients being younger (31 versus 45 months, P =
      .05). Group 2 patients had higher postoperative central venous pressures (17.8
      versus 14.1 mm Hg, P < .001) and oxygen saturations (86% versus 81%, P < .001)
      than did group 1 patients. There was no statistical difference between groups in
      the number of chest tube days or hospital days. There was 1 early death in group
      1 related to severe ventricular dysfunction and 1 late death in group 2 related
      to sepsis. Five patients in group 2 were readmitted to the hospital for drainage
      of a large chylothorax compared with none in group 1 (P < .02). CONCLUSIONS: We
      conclude that patients with an additional source of pulmonary blood flow after
      bidirectional cavopulmonary shunt have higher postoperative central venous
      pressures, have higher oxygen saturations, and are at risk for the late
      development of a chylothorax.

PMID- 7586415
TI  - Right ventricular performance and mass by use of cine MRI late after atrial
      repair of transposition of the great arteries.
AB  - BACKGROUND: The long-term adaptation of the right ventricle after atrial repair
      of transposition of the great arteries (TGA) remains a subject of major concern.
      Cine magnetic resonance imaging (MRI), with its tomographic capabilities, allows
      unique quantitative evaluation of both right and left ventricular function and
      mass. Our purpose was to use MRI and an age-matched normal population to examine
      the typical late adaptation of the right and left ventricles after atrial repair
      of TGA. METHODS AND RESULTS: Cine MRI was used to study ventricular function and
      mass in 22 patients after atrial repair of TGA. Images were obtained in short
      axis sections from base to apex to derive normalized right and left ventricular
      mass (RVM and LVM, g/m2), interventricular septal mass (IVSM, g/m2), RV and LV
      end-diastolic volumes (EDV, mL/m2), and ejection fractions (EF). Results 8 to 23
      years after repair were compared with analysis of 24 age- and sex-matched normal
      volunteers and revealed markedly elevated RVM, decreased LVM and IVSM, normal RV
      size, and only mildly depressed RVEF. Only 1 of 22 patients had clinical RV
      dysfunction, and this patient had increased RVM. CONCLUSIONS: Cine MRI allows
      quantitative evaluation of both RV and LV mass and function late after atrial
      repair of TGA. Longitudinal studies that include these measurements should prove
      useful in determining the mechanism of late RV failure in these patients. On the
      basis of these early data, inadequate hypertrophy does not appear to be the cause
      of late dysfunction in this patient group.

PMID- 7586413
TI  - Discriminating between preservation and reperfusion injury in human cardiac
      allografts using heart weight and left ventricular mass.
AB  - BACKGROUND: Myocardial edema caused by injury during preservation or reperfusion
      can affect cardiac function after heart transplantation. This study was designed
      to distinguish these forms of injury in human allografts. METHODS AND RESULTS: In
      15 donor hearts preserved in University of Wisconsin solution, heart weight (HW)
      was obtained immediately after explantation and after transport before
      implantation. Left ventricular mass (LVM) was calculated separately in 18
      patients with the use of epicardial two-dimensional echocardiograms obtained both
      before explantation from the donor and after transplantation and weaning from
      cardiopulmonary bypass. While changes in LVM could be due to preservation or
      reperfusion injury, changes in HW can only be due to edema occurring during
      transport. HW averaged 339 +/- 24 g (mean +/- SE) before and 340 +/- 24 g after
      transport (P = NS); however, LVM increased 14 g, from 164 +/- 8 to 178 +/- 11 g
      (P < .05, paired t test). LVM increased in 10 of 18 patients (56%). No
      correlation was demonstrated between duration of ischemia (mean, 172 +/- 13
      minutes) and changes in HW or LVM. Two patients died as a result of primary graft
      failure. In the first, HW increased 54 g, 2 SD above the mean. In the second, LVM
      increased 66 g, 2 SD above the mean, but HW changed minimally. CONCLUSIONS: While
      current preservation methods result in minimal change in HW during transport,
      reperfusion injury frequently increases LVM. LVM determination by two-dimensional
      echocardiography may prove valuable in detecting allograft injury.

PMID- 7586417
TI  - Radical outcome method. A new approach to critical pathways in congenital heart
      disease.
AB  - BACKGROUND: Treatment of congenital heart disease has entered a new era of
      healthcare delivery and cost containment. Critical pathway method (CPM) has been
      previously demonstrated by us to produce a significant reduction in average
      length of stay (ALOS) in hospital of -44%. A new approach, radical outcome method
      (ROM), has produced comparable results that appear to improve over time. The
      dynamic nature is examined. METHODS AND RESULTS: Two hundred consecutive patients
      with congenital heart disease were treated by a single surgeon at a single health
      maintenance organization (HMO) facility. ROM was used in all patients. This
      method uses seven critical moments at which shortening rather than confirmation
      of the ALOS is possible. This process is completed by the second post-operative
      day. Overall mortality was 1%. The 200 patients were divided into two consecutive
      groups of 100 patients to determine the effectiveness of ROM over time. Fifty
      sets were matched. ALOS hospital decreased by 29 days (mean, 0.6 d/set), P <
      .003. Thirty sets who underwent cardiopulmonary bypass had a 16% decrease (P <
      .03), and 20 sets in whom nonbypass procedures were performed had a decrease of
      16% (P < .02). ALOS in hospital for the 50 sets decreased from 3.7 to 3.1 days (
      16%, P < .003). Outcome data demonstrated no significant difference. CONCLUSIONS:
      ROM, a proactive approach to hospital stay, is a dynamic process that reduces
      ALOS in hospital. This is achieved by both reducing negative variation in the
      standard CPM and allowing for positive variation. Outcome data confirm that this
      approach can reduce ALOS in hospital while providing optimal patient care and
      family satisfaction, a standard for the new era of healthcare delivery.

PMID- 7586418
TI  - Noninvasive assessment of left internal mammary artery graft patency using
      transthoracic echocardiography.
AB  - BACKGROUND: Cardiac catheterization is the only practical method of assessing
      internal mammary artery graft patency. A noninvasive method would be useful in
      patients with recurrence of anginal symptoms after coronary artery bypass graft
      surgery. We hypothesized that transthoracic echocardiography could provide
      information on blood velocity and anatomy and therefore has the potential to
      allow measurement of blood flow. METHODS AND RESULTS: High-frequency (5 MHz)
      transthoracic echocardiography was performed on 41 consecutive patients (mean
      age, 67 +/- 6 years) who had had left internal mammary artery grafts to the left
      anterior descending coronary artery (LAD) and were undergoing coronary
      angiography because of recurrence of anginal symptoms. The results were compared
      with those from 19 patients (mean age, 58 +/- 11 years) in whom an ungrafted left
      internal mammary artery was assessed and with those from 15 patients (mean age,
      61 +/- 12 years) who had angiographically normal coronary arteries in whom the
      LAD was studied. Doppler velocity profiles of the left internal mammary graft
      were obtained in 35 of the 41 study patients (81%). In all cases, a biphasic
      pattern of blood flow was recorded that corresponded to systole and diastole. Two
      different flow patterns were observed. In 25 patients with a normal graft or
      moderate (< 70%) stenosis (group A), blood flow velocity was maximal during
      diastole. This pattern was also seen in the LAD control group. In 10 patients
      with severe (> 70%) graft stenosis (group B), blood velocity was maximal during
      systole, and low velocities were recorded during diastole. This pattern was also
      seen in the ungrafted internal mammary artery control group. The diastolic
      fraction of the velocity time integrals for group A was 0.77 +/- 0.07 and for
      group B was 0.27 +/- 0.01 (P < .05). A diastolic velocity time integral fraction
      < 0.5 predicted severe stenosis with a sensitivity and specificity of 100%. The
      ratio of systolic-to-diastolic peak velocities for group A was 0.54 +/- 0.26 and
      for group B was 3.45 +/- 0.74 (P < .05). A systolic-to-diastolic peak velocity
      ratio > 1 predicted severe stenosis with a sensitivity of 100% and specificity of
      85%. Mean graft blood flow was 63 +/- 21 mL/min. There was no significant
      difference in mean blood flow between any of the patient groups studied.
      CONCLUSIONS: High-frequency transthoracic echocardiography allows identification
      of the left internal mammary grafts and measurement of blood flow. Compared with
      patent grafts or those with moderate lesions, severe stenoses demonstrated
      different Doppler velocity patterns. Use of this technique may allow noninvasive
      detection of significant stenoses of the left internal mammary artery graft.

PMID- 7586419
TI  - Left ventricular dysfunction on exercise long-term after total repair of
      tetralogy of Fallot.
AB  - BACKGROUND: Excellent results regarding mortality are well recognized in the long
      term period after intracardiac repair of tetralogy of Fallot. However, it is
      still unclear how postoperative sequelae affect cardiac performance during
      exercise. METHODS AND RESULTS: Twenty-nine patients with tetralogy of Fallot were
      studied 16 +/- 2 years after intracardiac repair by use of radionuclide first
      pass ventriculography with an ultra-high-sensitive gamma camera at rest and at
      peak exercise on a semi-upright bicycle ergometer. The results were compared with
      those from 10 age- and sex-matched control subjects. Left and right ventricular
      ejection fraction and absolute ventricular volume were measured at rest and peak
      exercise. Regional right ventricular wall motion and diastolic function of the
      left ventricle were also assessed. Cardiac output of tetralogy was normally
      preserved both at rest and during exercise. Nevertheless, the incremental
      response of left ventricular ejection fraction during exercise was depressed in
      the patients. Left ventricular ejection fraction during exercise was inversely
      correlated with the right ventricular end-diastolic volume and the severity of
      pulmonary regurgitation. Regional wall motion at the right ventricular outflow
      tract was not decreased in the patients. Left ventricular diastolic function was
      not impaired in the patients compared with control subjects. CONCLUSIONS: Latent
      left ventricular dysfunction during exercise is related to an enlarged right
      ventricle due to pulmonary regurgitation after intracardiac repair of tetralogy.
      Careful follow-up is required in patients having significant pulmonary
      regurgitation.

PMID- 7586421
TI  - Ten-year institutional experience with palliative surgery for hypoplastic left
      heart syndrome. Risk factors related to stage I mortality.
AB  - BACKGROUND: We reviewed 212 consecutive patients who underwent stage I palliative
      surgery for hypoplastic left heart syndrome (HLHS) at our institution between
      January 1983 and June 1993. METHODS AND RESULTS: Six surgeons participated in the
      care of these patients. Follow-up is 97% complete. Preoperative anatomic and
      physiological factors and procedural features of the stage I operation were
      analyzed for impact on stage I mortality, survival to stage II palliation, and
      actuarial survival. Hospital mortality was not significantly lower during the
      second half of the study period (P = .242). Operative mortality was 46.2%.
      Multivariate analysis revealed improved stage I operative survival in patients
      with mitral stenosis (MS) and aortic stenosis (AS; P = .006). Additional risk
      factors for stage I mortality were a lower immediately pre-stage I pH (P = .034)
      and weight < 3 kg (P = .015). Overall first-year actuarial survival for MS/AS was
      59%, and it was 33% for all others (P = .001). Among stage I survivors, patients
      with MS/AS were more likely to survive to stage II palliation (P = .031).
      Analysis of actuarial survival of stage I survivors showed that a smaller
      ascending aorta (P < .001), aortic atresia (P < .001), and mitral atresia (P =
      .002) were all risk factors for intermediate death. CONCLUSIONS: Preoperative
      anatomic and physiological state are predictors of stage I mortality. HLHS
      anatomic subtype also influences intermediate outcome, most notably pre-stage II
      attrition. These data may be useful in choosing initial management for patients
      with HLHS.

PMID- 7586420
TI  - Sternotomy approach for the modified Blalock-Taussig shunt.
AB  - BACKGROUND: Since 1990, sternotomy has been the preferred approach for
      construction of a modified Blalock-Taussig shunt (MBTS) at Children's Hospital,
      Boston, Mass. In retrospect, we sought to test the hypothesis that this approach
      yields less mortality and morbidity than the traditional thoracotomy approach.
      METHODS AND RESULTS: One hundred four primary MBTSs with polytetrafluoroethylene
      grafts were constructed in patients from January 1988 through December 1992.
      Fifty-two shunts were constructed by thoracotomy approach and 52 by sternotomy
      approach. Fifteen of the thoracotomy patients were less than one month of age (8
      less than 7 days), while 36 of the sternotomy patients were less than 1 month of
      age (20 less than 7 days). There were 10 shunt failures and 3 hospital deaths in
      the thoracotomy group and 4 shunt failures with 6 hospital deaths in the
      sternotomy group. The overall hospital mortality rate for the group was 8.7% (9
      of 104). The operative route was not a significant predictor of hospital
      mortality (P = .30). However, there was a significant difference between the two
      operative approaches in shunt failure, with shunts that were created by
      thoracotomy four times more likely to fail than those created by the sternotomy
      route (odds ratio, OR, 3.88; 95% CI, 1.01 to 15.03; P = .049). The side of the
      shunt was also a significant predictor of failure with left-side MBTSs foru times
      more prone to failure (OR, 4.02; 95% CI, 1.19 to 15.25; P = .025). CONCLUSIONS:
      The sternotomy route is technically less challenging and is associated with fewer
      shunt failures than the classic thoracotomy approach. The potential theoretical
      disadvantages of this method for future sternal reentry for subsequent procedures
      was not apparent but requires prospective analysis.

PMID- 7586422
TI  - Hemodynamic characteristics of neonates following first stage palliation for
      hypoplastic left heart syndrome.
AB  - BACKGROUND: It is widely held that the postoperative course of patients with
      hypoplastic left heart syndrome (HLHS) after stage 1 palliation is characterized
      by hemodynamic instability, which in part may be due to excessive pulmonary blood
      flow. Hence, avoidance of alkalosis and the use of minimally oxygen-enriched
      inspiratory gas are thought by many to be important, although there is little
      pertinent published data. This study was undertaken to characterize the
      postoperative course and to determine whether the FIO2 and blood pH are related
      to indices of hemodynamic stability in these infants. METHODS AND RESULTS: The
      postoperative course of 25 consecutive infants undergoing first stage palliation
      for HLHS were retrospectively reviewed and the following data were obtained:
      arterial pressure, arterial blood gas measurements, the inotropic agents used,
      and multiple respiratory parameters. There was one operative death, and 2
      patients died within 2 days, but 22 were extubated (mean, 5.2 +/- 4.1 days after
      surgery). Hospital mortality was 24%. Mean pH was > or = 7.51 for the first 9
      hours after surgery and was > or = 7.45 for the entire period. The mean FIO2 was
      > or = 50% for the first 18 hours. The PaO2 was appropriate (37 +/- 6 mm Hg at 1
      hour after surgery, increasing to 45 +/- 5 mm Hg by hour 73). Only modest
      inotropic support was needed to maintain appropriate blood pressure. CONCLUSIONS:
      These data suggest that neither alkalosis nor relatively high inspired oxygen
      necessarily cause hemodynamic instability in these patients. To what extent these
      results are generalizable is unclear, but they suggest that there is nothing
      inherent with HLHS that mandates postoperative hemodynamic instability or
      unacceptable mortality.

PMID- 7586423
TI  - Intermediate-term outcome after intracardiac repair of associated cardiac defects
      in patients with atrioventricular and ventriculoarterial discordance.
AB  - BACKGROUND: Limited information is available concerning long-term results,
      especially systemic right ventricular (RV) or tricuspid valvular function, after
      intracardiac repair of anomalies associated with discordant atrioventricular (AV)
      and ventriculoarterial (VA) connections ("congenitally corrected transposition of
      the great arteries"). METHODS AND RESULTS: We retrospectively reviewed the
      intermediate-term follow-up of 28 patients, totaling 158 patient-years (median,
      60 months), after intracardiac repair involving closure of a ventricular septal
      defect (VSD) with or without additional surgery. Seven patients had VSD closure
      alone, 5 had VSD repair with pulmonary stenosis relief, and 16 had VSD closure
      with conduit insertion between left ventricle and main pulmonary artery. Hospital
      mortality was 4% (1 of 28 patients; 70% confidence limits, 0.07% to 12%) and the
      1-, 5-, and 10-year actuarial survival probabilities were 89%, 83%, and 83%,
      respectively. Twenty-one of 24 long-term survivors were in New York Heart
      Association functional class I and 3 were in class II. Sixteen of 24 patients
      showed increasing tricuspid regurgitation (TR) of more than moderate degree,
      which occurred within 3 years after surgery in 7 patients. Twelve of 22 patients
      showed deterioration of RV pump function, mainly (9 of 12 patients) within 3
      years postoperatively. The pulmonary to systemic flow ratio at the preoperative
      cardiac catheter study was significantly (P < .05) higher in patients who
      developed RV dysfunction (2.3 +/- 1.0, mean +/- SD) than in those with well
      maintained RV function (1.4 +/- 0.6). CONCLUSION: Intermediate-term results of
      intracardiac repair for AV and VA discordance were satisfactory in terms of
      survival and clinical functional status; however, there is concern about systemic
      RV dysfunction with development of TR relatively early after the operation.
      Alternative surgical approaches such as anatomic correction or Fontan repair for
      cases unsuitable for biventricular repair may improve the long-term results,
      including ventricular and valvular function.

PMID- 7586425
TI  - Thromboembolic complications after Fontan operations.
AB  - BACKGROUND: Despite the increasing recognition of thromboembolic complications of
      the Fontan procedure, data characterizing such events are limited. The total
      cavopulmonary connection is believed to be less prone to this complication than
      other modifications of Fontan operations. We examined our experience with
      thromboembolism after Fontan operations to better characterize these events and
      their relation to the type of Fontan operation performed. METHODS AND RESULTS: We
      retrospectively identified 70 patients who underwent a Fontan operation between
      January 1978 and March 1994. Patients were divided into three groups: (1) total
      cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit
      interposition. Fourteen patients (20%) developed a thromboembolic complication
      during a mean (+/- SD) follow-up of 5.2 +/- 4.7 years. The rate of thrombosis was
      similar in each group. The time from Fontan operation to thrombosis averaged 6.1
      +/- 5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient
      years. Twelve of the 14 thrombi were located within the venous circulation, 1 was
      in the left ventricle, and the location of 1 was undetermined. Six of the
      patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events,
      and 5 (36%) presented with other symptoms. Thromboembolic events occurred from
      the perioperative period to 15 years after surgery. CONCLUSIONS: Thromboembolic
      complications occur frequently after the Fontan operation and its modifications
      and are a cause of significant morbidity. The time of presentation varies
      greatly. The rate of thrombosis appears to be similar in all modifications of the
      Fontan operation.

PMID- 7586424
TI  - Influence of competitive pulmonary blood flow on the bidirectional superior
      cavopulmonary shunt. A multi-institutional study.
AB  - BACKGROUND: It is common practice to interrupt all alternative sources of
      pulmonary blood flow ("competitive flow") at the time of a bidirectional superior
      cavopulmonary anastomosis (BCPA), although the merits of this have not been
      systematically studied. METHODS AND RESULTS: We reviewed the early and medium
      term clinical and hemodynamic findings in 108 consecutive patients 3 weeks to 25
      years old (median, 1.9 years) undergoing BCPA at one of three institutions.
      Preoperatively, pulmonary blood flow was dependent on antegrade ventricular flow
      (n = 50), systemic-to-pulmonary shunts (n = 33), or mixed sources (n = 25).
      Postoperatively, competitive sources of pulmonary blood flow were left patent in
      43 of 108 patients (40%). There were four early (3.7%) and four late deaths, none
      related to persistence of competitive flow. After BCPA, patients with competitive
      flow had significantly higher systemic oxygen saturations at 1 hour (85% versus
      79%), 24 hours (84% versus 78%), and at hospital discharge (84% versus 78%) and
      required a shorter period of artificial ventilation (median, 9 versus 24 hours)
      and intensive care (median, 2 versus 4 days). Oxygen saturations at late follow
      up (median, 2.8 years; range, 1 to 7) did not differ (83% versus 82%). No patient
      developed pulmonary arteriovenous malformations. CONCLUSIONS: Competitive flow is
      well tolerated in the short and medium term after BCPA, and early postoperative
      systemic oxygen saturations are improved. The long-term influence of competitive
      flow on pulmonary arterial growth, arteriovenous malformation development, and
      ventricular function warrants investigation.

PMID- 7586427
TI  - Effects of elevated coronary sinus pressure on coronary blood flow and left
      ventricular function. Implications after the Fontan operation.
AB  - BACKGROUND: After the Fontan operation there is elevated systemic venous
      pressure, and the coronary sinus pressure (CSP) may also be elevated depending on
      the operative technique. Elevated CSP can potentially alter coronary perfusion
      and thereby be a cause for postoperative left ventricular (LV) dysfunction.
      METHODS AND RESULTS: The effects of elevated CSP on coronary blood flow (CBF) and
      LV function were evaluated in 14 isolated blood-perfused juvenile lamb hearts.
      After baseline measurements were made, CSP was elevated by a 10-minute inflation
      of a balloon catheter inserted into the coronary sinus via the hemiazygos vein in
      7 hearts (CSHT group) to cause moderate (phase I, approximately 15 mm Hg) and
      severe (phase II, approximately 30 mm Hg) elevations of mean CSP at a constant
      coronary perfusion pressure (80 mm Hg). The results were compared with results
      from 7 hearts continuously perfused without elevation of CSP (C group). Mean CSP
      in the CSHT group was elevated from 0.4 +/- 1.9 to 16.4 +/- 2.4 mm Hg during
      phase I and to 32.6 +/- 3.6 mm Hg during phase II. CBF in the CSHT group
      decreased to 89.7 +/- 5.2% in phase I and to 79.0 +/- 13.2% in phase II, and
      these values were significantly lower than those in the C group (98.5 +/- 6.7% in
      phase I and 106.8 +/- 16.0% in phase II; P < .05 each). There were no significant
      differences in maximum developed pressure (DP), max+dP/dt, max-dP/dt, or LV end
      diastolic pressure (LVEDP) at a fixed volume between the CSHT group and the C
      group either in phase I or phase II. The time constant of pressure decline during
      LV isovolumic relaxation (tau) showed no significant difference in phase I, but
      in phase II tau was significantly higher in the CSHT group (116.2 +/- 7.8%) than
      that in the C group (106.3 +/- 8.5%; P < .05). CONCLUSIONS: Elevated CSP on a
      short-term basis did not affect the LV systolic function indexes (max DP,
      max+dP/dt), max-dP/dt, or LVEDP at a fixed volume, but tau did appear to worsen
      and CBF decreased during CSP elevation. These actions might have deleterious
      effects on the LV over a longer time period.

PMID- 7586426
TI  - Bidirectional Glenn. Is accessory pulmonary blood flow good or bad?
AB  - BACKGROUND: The bidirectional Glenn (BDG) is frequently used in the staged
      surgical management of single ventricle patients. Controversy exists whether
      accessory pulmonary blood flow (APBF) sources should be left at the time of the
      BDG to augment systemic saturation or should be eliminated to reduce volume load
      of the ventricle. The present study was a retrospective review to assess the
      influence of APBF on outcome after the BDG. METHODS AND RESULTS: Ninety-two
      patients have undergone BDG at our institute during the interval from 1986
      through 1994. At the time of BDG, 40 patients had either a systemic-to-pulmonary
      artery shunt or patent right ventricular outflow tract as an additional source of
      pulmonary blood flow. Fifty-two patients had elimination of APBF. There were
      three operative deaths (two with and one without APBF) and four procedures (two
      in each group) that failed and required subsequent revision. Thus, there were 85
      patients who underwent successful operation. Effusions (defined as chest tube
      drainage exceeding 7 days' duration) occurred in 8 of 85 patients; this
      complication was seen in 7 of 36 patients (19%) with APBF and 1 of 49 patients
      (2%) without APBF (P < .05). There were 11 deaths, including 6 patients (17%)
      with APBF, 2 patients (4%) without APBF, and 3 of the patients (75%) who had a
      failed BDG. CONCLUSIONS: The data suggest that morbidity and mortality are lower
      in patients in whom APBF is eliminated at the time of the BDG.

PMID- 7586428
TI  - Loss of sinus rhythm after total cavopulmonary connection.
AB  - BACKGROUND: Total cavopulmonary connection (TCPC) to repair functional single
      ventricle involves the sinus node area, in contrast to the Fontan procedure. We
      compared ECG findings after TCPC and Fontan to evaluate the impact of the
      cavopulmonary connection on sinus rhythm postoperatively. METHODS AND RESULTS:
      The Fontan group consisted of 17 patients repaired at 7.8 +/- 3.1 years of age
      (mean +/- SD): 11 for tricuspid or pulmonary atresia (TA/PA) and 6 for single
      ventricle. The TCPC group consisted of 19 patients repaired at 5.1 +/- 3.2 years
      of age (mean +/- SD) (P < .001): 9 for TA/PA, 4 for single ventricle, and 6 for
      hypoplastic left heart syndrome. Mean follow-up after Fontan was 7.7 +/- 2.7
      years versus 2.8 +/- 1.6 years for TCPC (P < .001). Preoperative ECGs on all TCPC
      patients showed sinus rhythm (SR), whereas 16 of 17 Fontan patients had SR and
      one had nonsinus atrial rhythm (NSAR) since birth. On the first postdischarge
      ECG, 12 of 19 TCPC patients (63%) were in SR, 4 were in junctional rhythm (JR),
      and 3 were in NSAR. In comparison, 15 of 17 Fontan patients (88%) were in SR with
      1 of 17 in NSAR and 1 in supraventricular tachycardia (P < .05 with chi 2 test).
      By 2 years postoperatively, only 6 of 15 TCPC patients available for follow-up
      (40%) were in SR, with 7 of 15 in JR and 2 of 15 in NSAR. By contrast, 13 of 17
      Fontan patients (76%) remained in SR, with 1 in NSAR and 3 in JR (P < .05 with
      chi 2 test). TCPC patients with loss of SR did not differ from other patients in
      the group in age at repair, preoperative diagnosis, or surgeon performing the
      procedure. CONCLUSIONS: This significant incidence of loss of SR temporally
      related to surgery suggests that operative compromise of the sinus node area is
      common with TCPC.

PMID- 7586429
TI  - Development of pulmonary arteriovenous fistulae in children after cavopulmonary
      shunt.
AB  - BACKGROUND: The cavopulmonary shunt procedure is now used for palliation of
      complex congenital heart lesions in infants. While pulmonary arteriovenous
      fistulae (PAVF) are a well-known complication of this surgery in older patients,
      no study of the prevalence of this condition in children and young infants has
      been reported. METHODS AND RESULTS: We compared 29 patients with cavopulmonary
      shunts or total caval exclusion with 53 control subjects evaluated by contrast
      echocardiography at the University of California, San Francisco. The primary
      cardiac lesion, age at the time of surgery, type of right heart bypass procedure,
      provision of auxiliary pulmonary blood flow, and changes in oxygen saturation
      over time were compared. The prevalence of PAVF in children after cavopulmonary
      anastomosis is 60%, higher than previously reported. The prevalence is
      significantly higher in infants < 6 months old and in those with a heterotaxy
      syndrome. The provision of an additional source of pulsatile, pulmonary blood
      flow appears to have little effect on the development of PAVF. Patients who
      developed PAVF had arterial oxygen saturations at the time of discharge from
      surgery similar to those who did not develop them. Those with PAVF had
      significantly lower arterial and pulmonary venous oxygen saturations at follow-up
      as a result of their intrapulmonary shunt. CONCLUSIONS: Contrast echocardiography
      provides a sensitive method for the detection of PAVF. While the origins, natural
      history, and ultimate clinical significance of PAVF in children after
      cavopulmonary anastomosis are unclear, surveillance by contrast echocardiography
      is indicated for all patients who have had this procedure because PAVF may cause
      significant intrapulmonary right-to-left shunting in some patients.

PMID- 7586432
TI  - Comparison by computerized numeric modeling of energy losses in different Fontan
      connections.
AB  - BACKGROUND: Different surgical techniques for creating a Fontan circulation can
      be used. The option of including an atrium in the circuit, or the technique used
      for connecting the caval veins to the pulmonary artery in a total cavopulmonary
      connection, frequently is empirical and is based on personal experience and
      preference. The hemodynamic and energetic differences between the different
      circuits are small, and short-term results are comparable. However, small,
      energetic differences may have significant implications for the long-term follow
      up. The finite element method allows a computer-based modeling of the flow
      dynamics and pressure losses. It permits comparison of different Fontan
      connections in a single patient with identical geometry and functional
      conditions. METHODS AND RESULTS: We compared the atriopulmonary connection with
      different types of cavopulmonary connections, which differed in the degree of
      symmetry of implantation of both caval veins into the right pulmonary artery.
      Based on anatomic models and physiological flow dynamics, three-dimensional
      geometries and finite element meshes were created with PATRAN; flows were
      calculated with POLYFLOW (B), and results were visualized with DATA VISUALIZER.
      CONCLUSIONS: The atriopulmonary connection produces higher energy losses than the
      cavopulmonary connection (+/- 1 mm Hg at rest). The cavopulmonary connection is
      more efficient when the connection of the caval veins to the pulmonary artery is
      asymmetrical.

PMID- 7586431
TI  - Induction of interleukin-8 messenger RNA in heart and skeletal muscle during
      pediatric cardiopulmonary bypass.
AB  - BACKGROUND: Interleukin-8 (IL-8), the major neutrophil chemoattractant factor,
      contributes to inflammatory tissue injury by activating neutrophils and promoting
      their migration into tissue. IL-8 levels increase in serum of patients undergoing
      cardiopulmonary bypass (CPB). The purpose of this study was to determine if IL-8
      gene expression is activated in tissues subjected to CPB with or without
      hypothermic arrest. METHODS AND RESULTS: IL-8 transcript levels were measured by
      ribonuclease protection in samples of human atrium and skeletal muscle from
      children before and after CPB for repair of congenital heart defects. Results
      were quantified by PhosphorImager. Atrial IL-8 mRNA levels increased during CPB
      in 14 of 16 patients tested (median increase, 2.9-fold; P = .0029). In skeletal
      muscle, IL-8 mRNA increased in 11 of 12 patients (median, 12-fold; P = .012).
      Degree of IL-8 induction in atrium and muscle was not directly associated with
      total support time or cross-clamp time. Transcript increase in skeletal muscle
      occurred with or without a period of circulatory arrest, suggesting that the
      stimulus of CPB alone was sufficient to induce message production. Baseline
      values for IL-8 mRNA varied widely among patients in atrium and skeletal muscle.
      In situ hybridization analysis revealed diffuse increase in IL-8 mRNA throughout
      the tissue after CPB, with striking increase in some small veins. CONCLUSIONS: We
      conclude that production of IL-8 mRNA occurs in most patients during CPB in both
      myocardium and skeletal muscle. This may result in high local IL-8
      concentrations, contributing to the tissue injury after CPB.

PMID- 7586430
TI  - Improved preservation of saphenous vein grafts by the use of glyceryl trinitrate
      verapamil solution during harvesting.
AB  - BACKGROUND: High-pressure distension during harvesting damages the saphenous vein
      (SV) and may contribute to subsequent coronary artery bypass graft (CABG)
      occlusion. Application of vasodilator agents to the SV during harvesting may
      reduce the need for high-pressure distension and improve graft quality. We tested
      the effects of a vasodilator solution containing glyceryl trinitrate and
      verapamil (GV) or the conventional agent papaverine (Pap) on the pressure
      necessary to overcome SV spasm and on the structure and biochemistry of the SV
      graft. METHODS AND RESULTS: Thirty-six patients undergoing CABG were randomly
      allocated to receive an application of either topical and intraluminal GV
      solution, topical Pap, or topical and intraluminal Ringer's solution (untreated)
      to the SV during harvesting. The peak and mean pressures required to distend the
      vein were recorded. Samples of SV were taken for microscopy and biochemical
      analysis just before we performed the anastomosis. The percentage of endothelial
      coverage was calculated by area measurements of stained en face preparations of
      the vein intima. The results for peak pressures (mmHg) were: untreated, 479.2 +/-
      27.5; Pap, 384.8 +/- 29.0; and GV, 309.5 +/- 28.3 (P < .001, GV plus Pap versus
      untreated); and the results for mean pressures (mm Hg) were untreated, 136.2 +/-
      9.6; Pap, 102.2 +/- 10.8; and GV, 98.0 +/- 8.3 (P < .01, GV plus Pap versus
      untreated). The results for endothelial cover (%) were: untreated, 43.7 +/- 7.0;
      Pap, 44.1 +/- 9.2; and GV, 68.7 +/- 7.0 (P < .05, GV versus Pap); and the results
      for ATP (nmol/g wet wt) were: untreated, 67.3 +/- 12.7; Pap, 112.0 +/- 19.4; and
      GV, 132.5 +/- 22.7 (P < .05, GV plus Pap versus untreated). CONCLUSIONS: First,
      pharmacological treatment of SV during harvesting, especially with GV solution,
      allows the use of a lower distension pressure and reduces the breakdown of high
      energy phosphates in the vein wall. Second, topical and intraluminal use of GV
      solution during vein harvesting improves endothelial coverage compared with the
      topical use of Pap or no pharmacological treatment.

PMID- 7586433
TI  - Determinants of cerebral oxygenation during cardiac surgery.
AB  - BACKGROUND: Neuropsychological deficits after cardiac surgery are attributed to
      the side effects of cardiopulmonary bypass (CPB). To protect the brain from
      ischemic damage, the influences of temperature, blood pressure, blood gases, acid
      base status, and hemodilution on cerebral oxygenation have to be elucidated and
      quantified. METHODS: Forty-one consecutive patients were investigated during
      cardiac surgery while on CPB. Operative management included moderate hypothermia
      of 26 degrees C and the alpha-stat pH management. With near-infrared
      spectrophotometry, changes in oxygenated hemoglobin (HbO2, representing oxygen
      delivery) and oxidized cytochrome a,a3 (CtO2, cellular oxygenation) in brain
      tissue were obtained noninvasively. In addition, venous saturation of the brain
      was measured via a catheter in the jugular bulb (SBJO2). The influence of
      operative management parameters on cerebral oxygenation was calculated by
      univariate and multiple regression analyses. RESULTS: Before and after CPB there
      was no significant multivariate determinant of cerebral oxygenation. During CPB,
      HbO2 depended solely on PCO2 (P < .01; r = .89). CtO2 was determined by pH (P <
      .01), esophageal temperature (P < .01), PCO2 (P < .01), and Hb (P < .01). These
      parameters explained nearly all changes of the cytochrome measurements during CPB
      (r = .99). Arterial PCO2 (P < .01) and pH (P < .01) influenced brain venous
      oxygen saturation (SBJO2; r = .98). CONCLUSIONS: Cerebral oxygenation is
      autoregulated during cardiac surgery before and after CPB. During CPB, Hb,
      temperature, pH, and PCO2 determined at least 85% of all changes in cerebral
      oxygenation. The main causes of impaired cerebral oxygenation are the decrease in
      Hb with hemodilution, vasoconstriction due to hypocapnia, and the leftward shift
      of the Hb binding curve in alkalosis and hypothermia.

PMID- 7586434
TI  - Influence of temperature on neutrophil trafficking during clinical
      cardiopulmonary bypass.
AB  - BACKGROUND: The adhesion of neutrophils to endothelial cells and their subsequent
      transendothelial migration play a major role in inflammatory damage elicited by
      cardiopulmonary bypass (CPB) because these events are linked to the release of
      cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking
      in relation to systemic temperature during clinical CPB have not yet been
      characterized. METHODS AND RESULTS: Twenty case-matched patients undergoing warm
      (31.8 +/- 0.4 degrees C) or cold (26.3 +/- 0.5 degrees C, P < .0001 versus warm)
      bypass were studied. Blood samples were simultaneously collected from the right
      and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of
      C3a, P- and E-selectins, elastase, and interleukin-8 were determined by
      immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement
      activation, (2) a fall in soluble E-selectin consistent with an increased
      adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected
      to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase,
      suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise
      in interleukin-8 that is likely to promote transendothelial migration of adherent
      neutrophils. All of these changes occurred in the two groups of patients and were
      significant compared with prebypass values. However, in none of the groups was
      there a significant difference between right and left atrial values for any of
      the markers. The single difference between cold and warm bypass patients was a
      significant reduction of elastase release in the cold group (P < .001 versus the
      warm group). CONCLUSIONS: Clinical CPB is associated with biological changes
      suggesting the occurrence of neutrophil trafficking. Hypothermia provides only
      partial protection through a reduced release of elastase. Overall, these results
      reinforce the rationale for the development of therapeutic strategies targeted at
      blunting the neutrophil-mediated component of bypass-induced inflammatory damage.

PMID- 7586435
TI  - Intermittent warm blood cardioplegia. Warm Heart Investigators.
AB  - BACKGROUND: Warm heart surgery implies continuous perfusion with normothermic
      blood cardioplegia. Interruption of cardioplegia, however, facilitates
      construction of distal coronary anastomoses and is the method practiced by many
      surgeons. To determine whether intermittency is harmful, we present results from
      720 coronary bypass patients, protected with intermittent antegrade warm blood
      cardioplegia, that were derived from a previous study of normothermic versus
      hypothermic cardioplegia. METHODS AND RESULTS: Mean +/- SD age was 60.8 +/- 9.0
      years; 27% of cases were urgent; 16% of patients had > 50% left main stenosis,
      and 19% had grade III or IV ventricles. A mean of 3.2 +/- 0.9 grafts was
      constructed. The average aortic cross-clamp time was 61.8 +/- 22.2 minutes. The
      longest single time off cardioplegia (LTOC) averaged 11.4 +/- 4.0 minutes per
      patient. The cumulative time off cardioplegia as a percentage of the cross-clamp
      time (PTOC) was 48.2 +/- 18.6% per patient. LTOC and PTOC were divided into
      quartiles (LTOC, < 10, 10 to 11, 12 to 13, and > 13 minutes; PTOC, < 36%, 36% to
      49%, 50% to 62%, and > 62%) and related to the prespecified composite outcome of
      mortality, myocardial infarction according to serial CK-MB sampling, and low
      output syndrome (LOS). Longer LTOC was harmful (event rates per quartile, 13.5%,
      10.3%, 10.9%, and 19.0%; P = .046), whereas longer PTOC was protective (16.1%,
      17.2%, 9.4%, and 10.6%; P = .07). Stepwise logistic regression was performed,
      controlling for demographic and angiographic predictors. In the multivariate
      models, LTOC remained detrimental (P = .07) and PTOC remained beneficial (P =
      .053). Additional modeling after entering surgeon identity (P < .001) into the
      risk equation eliminated the PTOC effect, whereas LTOC remained predictive of
      adverse outcomes (P = .053; odds ratio, 1.06; 95% CI, 1.00, 1.13). CONCLUSIONS:
      The data indicate that a reasonable margin of safety exists with intermittent,
      antegrade warm blood cardioplegia. Repeated interruptions of warm blood
      cardioplegia are unlikely to lead to adverse clinical results if single
      interruptions are < or = 13 minutes.

PMID- 7586436
TI  - Steroid inhibition of cytokine-mediated vasodilation after warm heart surgery.
AB  - BACKGROUND: Peripheral vasodilation, a potentially adverse effect of warm heart
      surgery, may be mediated by the perioperative release of cytokines.
      Corticosteroids may abolish cytokine production and vasodilation. We investigated
      cytokine production and its inhibition by steroids in patients undergoing
      elective coronary bypass surgery. METHODS AND RESULTS: Twenty-five patients
      undergoing coronary bypass surgery with normothermic cardiopulmonary bypass
      received either preoperative steroid (Solumedrol 250 mg IV, n = 16) or no steroid
      (n = 9, control group). Blood samples were obtained serially for 24 hours and
      assayed for interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-8
      (IL-8). In the control patients, the IL-6, TNF, and IL-8 levels were elevated
      postoperatively and peaked between 3 and 6 hours after surgery (IL-6, 1330 +/-
      295 [mean +/- SEM] pg/mL; TNF, 18.4 +/- 9.8 pg/mL; and IL-8, 150 +/- 51 pg/mL).
      Cytokine release was abolished in patients receiving preoperative corticosteroid
      (IL-6, 75 +/- 38 pg/mL; TNF, 2.6 +/- 0.5 pg/mL; and IL-8, 33 +/- 6.7 pg/mL; P <
      .05). Patients receiving steroid premedication had higher arterial pressure,
      lower cardiac index, and higher systemic vascular resistance, indicating less
      vasodilation. CONCLUSIONS: Our findings demonstrate that cytokine production
      occurs after normothermic cardiopulmonary bypass. Preoperative administration of
      steroids abolishes cytokine release and vasodilation.

PMID- 7586437
TI  - Hypothermia during cardiopulmonary bypass delays but does not prevent neutrophil
      endothelial cell adhesion. A clinical study.
AB  - BACKGROUND: An accurate evaluation of warm heart surgery cannot be limited to the
      assessment of the myocardial effects of warm blood cardioplegia but should also
      address the effects of systemic normothermia on the inflammatory response to
      cardiopulmonary bypass. A major component of this response is the endothelial
      adhesion of neutrophils, because it is linked to the release of cytotoxic
      compounds. This study was designed (1) to characterize the bypass-induced changes
      in the expression of neutrophil adhesion molecules (L-selectin and beta 2
      integrins) and (2) to assess the influence of bypass temperature on these
      changes. METHODS AND RESULTS: Twenty case-matched patients undergoing open-heart
      procedures were divided into two equal groups according to the core temperature
      during cardiopulmonary bypass: warm (33.4 +/- 0.3 degrees C) or cold (27.1 +/-
      0.4 degrees C, P < .0001 versus warm). Arterial blood samples were collected
      before, during, and 30 minutes after bypass and processed for the expression of L
      selectin and beta 2-integrins (CD11a, CD11b, and CD11c) with flow cytometry. Warm
      bypass was associated with an early and sustained upregulation of CD11b. In
      contrast, hypothermia resulted in a strikingly less pronounced CD11b upregulation
      during bypass. However, CD11b expression sharply increased thereafter so that 30
      minutes after bypass, it was no longer significantly different between the two
      groups. Changes in CD11c expression grossly paralleled those described for CD11b.
      Neither CD11a nor L-selectin changed significantly from baseline values in either
      group. CONCLUSIONS: Clinical cardiopulmonary bypass is associated with a marked
      upregulation of the neutrophil CD11b and CD11c integrins. Hypothermia delays but
      does not prevent the increased expression of these adhesion molecules, which
      could consequently represent logical targets for interventions designed to blunt
      the neutrophil-mediated component of bypass-induced inflammatory tissue damage.

PMID- 7586440
TI  - Preoperative selection of patients with severely impaired left ventricular
      function for coronary revascularization. Role of low-dose dobutamine
      echocardiography and exercise-redistribution-reinjection thallium SPECT.
AB  - BACKGROUND: Both thallium imaging and low-dose dobutamine echocardiography have
      been proposed to predict the reversibility of left ventricular (LV) dysfunction
      in patients with coronary disease. The present study was designed to evaluate
      whether the use of these techniques during the preoperative assessment of
      coronary patients with depressed LV function can improve our ability to identify
      those likely to have improved LV function after surgery. METHODS AND RESULTS:
      Forty consecutive patients (age, 60 +/- 10 years) with coronary disease and an
      ejection fraction < or = 35% underwent dobutamine echocardiography (10
      micrograms/kg per minute) and exercise-redistribution-reinjection thallium single
      photon emission computed tomography (SPECT) before coronary revascularization by
      bypass surgery (n = 33) or angioplasty (n = 7). Recovery of LV function was
      evaluated by echocardiography 5.3 +/- 2.4 months after revascularization.
      According to the changes in end-systolic volume and ejection fraction after
      revascularization, the patients were categorized into groups with (n = 19) and
      without (n = 21) postoperative functional improvement, defined as a > 5% increase
      in ejection fraction and > 10 mL decrease in end-systolic volume. Before
      revascularization, patients with improved postoperative function had smaller end
      diastolic volume and less wall motion abnormalities than those with persistent
      dysfunction. They also showed greater improvement of wall motion score with
      dobutamine (6.1 +/- 2.4 versus 1.8 +/- 4.2 grades, P < .001) and smaller thallium
      defect score after exercise (38 +/- 12 versus 47 +/- 14 grades, P = .04).
      Discriminant analysis selected the improvement in wall motion score with
      dobutamine and baseline end-diastolic volume as independent predictors of
      postoperative recovery. Consideration of both parameters allowed prediction of
      functional outcome in 84% of the patients with and 81% of those without
      postoperative improvement. CONCLUSIONS: Among the parameters commonly available
      before surgery in coronary patients with depressed LV function, the maintenance
      of significant inotropic reserve, the severity of LV remodeling, and the
      magnitude of the perfusion defect after exercise can predict the reversal of LV
      dysfunction after revascularization.

PMID- 7586438
TI  - Modified maze procedure for patients with atrial fibrillation undergoing
      simultaneous open heart surgery.
AB  - BACKGROUND: Persistent atrial fibrillation (AF) leaves patients symptomatic and
      at increased risk of thromboembolism even after otherwise successful cardiac
      surgery. METHODS AND RESULTS: To treat AF secondary to cardiac lesions requiring
      surgery, we combined a modified maze procedure in 101 patients simultaneously
      undergoing valvular procedures (87), repair of congenital anomalies (12), and
      other procedures (2), including 24 repeat operations. Duration of AF varied from
      0.1 to 30 years (average +/- SD, 8.8 +/- 7.0 years); the f-wave voltage ranged
      from 0 to 0.45 mV (0.15 +/- 0.09 mV); and cardiothoracic ratio varied from 40% to
      99% (63 +/- 9%). Aortic cross-clamp time varied from 75 to 229 minutes (138 +/-
      31 minutes), with bypass time ranging from 119 to 326 minutes (217 +/- 42
      minutes). There were two early deaths (2%), no late deaths, and one episode of
      transient neurological ischemic attack in follow-up ranging from 1.0 to 3.1
      years, for a total of 190 patient-years. Postoperative rhythms were sinus in 83
      patients (82%), junctional in 4 (4%), and persistent AF in 14 (14%), each of whom
      had mitral valve disease. Patients with other underlying pathology had complete
      recovery of atrial rhythm. A normal-sized A wave was detected in 88% for
      transtricuspid flow and in 73% for transmitral flow, suggesting concomitant
      recovery of atrial contraction. Among 36 patients without mechanical valves, 30
      (83%) with atrial rhythm and contraction have been taken off anticoagulation
      therapy, including 10 who are free of all medication. CONCLUSIONS: The results
      suggest that the combined approach is safe, effective, and indicated in patients
      who are judged capable of tolerating the procedure and likely to regain atrial
      rhythm.

PMID- 7586439
TI  - Synergistic effect of vascular endothelial growth factor and basic fibroblast
      growth factor on angiogenesis in vivo.
AB  - BACKGROUND: Recent studies have suggested that vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) may have synergistic effects on
      the induction of angiogenesis in vitro. Therefore, we investigated the hypothesis
      that the simultaneous administration of VEGF and bFGF, each having been
      previously shown to independently enhance collateral development in an animal
      model of hind limb ischemia, could have a synergistic effect in vivo. METHODS AND
      RESULTS: Ten days after surgical induction of unilateral hind limb ischemia, New
      Zealand White rabbits were randomized to receive either VEGF 500 micrograms alone
      (n = 6), bFGF 10 micrograms alone (n = 7), VEGF 500 micrograms, immediately
      followed by 10 micrograms bFGF (n = 7), or vehicle only (control animals, n = 8)
      in each case administered intra-arterially via a catheter in the internal iliac
      artery of the ischemic limb. BP ratio (BPR, ischemic/healthy limb) at day 10 for
      the VEGF+bFGF group was 0.82 +/- 0.01, much superior (P < .0005) to that of
      either the VEGF group (0.52 +/- 0.02) or the bFGF group (0.57 +/- 0.02). This
      outcome persisted at day 30: BPR in the VEGF+bFGF group (0.91 +/- 0.02) exceeded
      that of the control group (0.49 +/- 0.05, P < .0001), the VEGF group (0.65 +/-
      0.03, P < .0005), or the bFGF group (0.66 +/- 0.03, P < .0005). Serial
      angiography demonstrated a progressive increase in luminal diameter of the stem
      collateral artery and the number of opacified collaterals in the thigh of the
      ischemic limbs in all groups. Stem artery diameter with VEGF+bFGF (1.34 +/- 0.07
      mm) on day 30 was significantly (P < .05) greater than with either VEGF (1.09 +/-
      0.09) or bFGF (1.18 +/- 0.06) alone. Capillary density was significantly greater
      (P < .05) in VEGF+bFGF animals (275 +/- 20 mm2) compared with VEGF (201 +/- 8) or
      bFGF (209 +/- 15). CONCLUSIONS: Combined administration of VEGF and bFGF
      stimulates significantly greater and more rapid augmentation of collateral
      circulation, resulting in superior hemodynamic improvement compared with either
      VEGF or bFGF alone. This synergism of two angiogenic mitogens with different
      target cell specificities may have important implications for the treatment of
      severe arterial insufficiency in patients whose disease is not amenable to direct
      revascularization.

PMID- 7586443
TI  - Can ischemic preconditioning ensure optimal myocardial protection when delivery
      of cardioplegia is impaired?
AB  - BACKGROUND: Ischemic preconditioning is a potent protective intervention that is
      effective in all species studied. We have previously shown it to be as effective
      as cardioplegia; however, we have also shown that their combined use does not
      afford greater protection than the use of either alone. In the present study we
      investigated whether coincident ischemic preconditioning could compensate for
      inadequate cardioplegic protection when the delivery of cardioplegia was
      impaired, such as occurs in the presence of severe coronary stenosis or
      occlusion. METHODS AND RESULTS: Isolated rat hearts were subjected to 30 minutes
      of global ischemia followed by 40 minutes of reperfusion. Four groups of hearts
      (n = 12 per group) were studied: group 1, controls (no intervention); group 2,
      cardioplegia administered to hearts with a proximally occluded coronary artery;
      group 3, ischemic preconditioning applied before ischemia; and group 4, ischemic
      preconditioning and cardioplegia given in combination to hearts with a proximally
      occluded coronary artery. The postischemic recovery of left ventricular (LV)
      developed pressure (LVDP), expressed as a percentage of preischemic values, was
      significantly greater (P < .05) in preconditioned hearts (64 +/- 3%) than in
      control hearts (24 +/- 4%) or hearts treated with suboptimal cardioplegia (43 +/-
      5%). Hearts with preconditioning plus cardioplegia recovered to an extent similar
      to that seen with preconditioning alone (59 +/- 2%). LV end-diastolic pressure
      was greater in control hearts (58 +/- 4 mm Hg) than in hearts with cardioplegia
      (41 +/- 4 mm Hg; P < .05 versus group 1) despite the incomplete delivery of the
      cardioplegia; the best protection was observed in preconditioned hearts and
      hearts with preconditioning plus cardioplegia (24 +/- 1 and 26 +/- 2 mm Hg,
      respectively; P < .05 versus groups 1 and 2). CONCLUSIONS: When the delivery of
      cardioplegia was impaired, myocardial protection (postischemic LVDP) was better
      served by ischemic preconditioning. Under the same conditions, the combination of
      cardioplegia plus preconditioning afforded superior protection compared with
      cardioplegia alone. These results may be of clinical interest since most patients
      who undergo surgery for ischemic heart disease suffer from severe coronary artery
      lesions that can prevent the adequate delivery of cardioplegia.

PMID- 7586441
TI  - Left ventricular function after extended hypothermic preservation of the heart is
      dependent on functional coronary capillarity.
AB  - BACKGROUND: A growing body of knowledge has led to the hypothesis that injury to
      the microcirculation during hypothermic myocardial preservation may result in
      decreased contractility of hearts upon reperfusion. METHODS AND RESULTS: To test
      this hypothesis, we examined the relationship between no-reflow and left
      ventricular function after hypothermic cardiac preservation after reperfusion
      with solutions containing dilute whole blood (DWB) or washed red blood cells
      (K2RBC). Rat hearts were arrested with high-potassium cardioplegia, then flushed
      and stored for 6 hours in low-potassium cardioplegia at 4 degrees C. Hearts were
      reperfused at a constant flow rate (4 mL/min) with K2RBC for 60 minutes (group 1,
      n = 5) or DWB for 7 minutes followed by 53 minutes of K2RBC (group 2, n = 5).
      Left ventricular developed pressure (LVDP) was measured with an intraventricular
      balloon. Immediately after functional assessment, hearts were perfused with an
      india ink solution to mark flow, then glutaraldehyde. Morphometric techniques
      were used to determine the degree of capillary compression [delta d(c)], perfused
      capillary number per fiber area [QA(0)P], and perfused capillary surface area per
      fiber volume [Sv(c,f)P]. Capillaries were moderately compressed in both groups
      after reperfusion (group 1, 19 +/- 1%; group 2, 20 +/- 1%). QA(0)P and Sv(c,f)P
      were highly correlated with delta d(c) in hearts reperfused with K2RBC (r = .92
      and r = .92; P < .01). Although statistically significant, the correlation was
      not as strong in DWB-reperfused hearts (r = .66 and r = .67; P < .05). LVDP was
      correlated to QA(0)P and Sv(c,f)P (r = .86 and r = .87, respectively) for groups
      1 and 2. CONCLUSIONS: The weaker correlation between capillary perfusion and
      capillary compression in DWB-reperfused hearts suggests that factors other than
      compression contribute to no-reflow after hypothermic preservation. Regardless of
      the composition of the reperfusate, recovery of left ventricular function after
      hypothermic ischemia is directly related to coronary capillary perfusion upon
      reperfusion.

PMID- 7586445
TI  - Effects of endothelin-1 and endothelin-A receptor antagonist on recovery after
      hypothermic cardioplegic ischemia in neonatal lamb hearts.
AB  - BACKGROUND: Prior studies suggest an important role for coronary endothelium in
      ischemia/reperfusion (I/R) injury. Decreased endothelial release of the
      vasodilator nitric oxide occurs after I/R, but the role of the endothelium
      derived vasoconstrictor endothelin-1 (ET-1) in I/R is unknown. METHODS AND
      RESULTS: We measured plasma ET-1 concentrations by radioimmunoassay in isolated
      blood-perfused neonatal lamb hearts before and after 2 hours of 10 degrees C
      cardioplegic ischemia and examined the effects of ET-1 and the endothelin-A (ET
      A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts.
      ET-1 levels in coronary sinus blood before ischemia and at 0 and 30 minutes of
      reperfusion in 8 control hearts were constant (2.2 +/- 1.2 fmol/L, 2.2 +/- 1.3
      fmol/L, and 2.5 +/- 1.0 fmol/L, respectively). In group 2 (n = 6), 10 mumol/L of
      BE-18257B was given just before reperfusion. In group 3 (n = 8), 10 pmol/L ET-1
      was given just before the start of reperfusion. At 30 minutes of reperfusion, the
      ET-A antagonist hearts had significantly greater recovery of LV systolic
      (positive dP/dt and dP/dt at V10) and diastolic function (negative dP/dt),
      coronary blood flow (CBF), and MVo2 compared with controls (P < .05). The ET-1
      hearts showed significantly reduced recovery of LV systolic (positive maximum and
      volume-normalized dP/dt) and diastolic (negative maximum dP/dt) function, CBF,
      and myocardial oxygen consumption compared with controls (P < .05). CONCLUSIONS:
      These results, combined with prior studies, suggest that I/R causes reduced
      production of endogenous vasodilators (eg, nitric oxide), leaving unopposed the
      vasoconstriction that is caused by the continued presence of ET-1. This imbalance
      may contribute to I/R injury. ET-A receptor antagonists may be useful therapeutic
      agents in reducing the injury that results from I/R.

PMID- 7586444
TI  - Improved protection of the hypertrophied left ventricle by histidine-containing
      cardioplegia.
AB  - BACKGROUND: Myocardial hypertrophy has been shown to lead to increased
      susceptibility to ischemia with accelerated loss of high-energy nucleotides,
      greater accumulation of H+ and lactate, and earlier onset of contracture. METHODS
      AND RESULTS: To determine whether promoting anaerobic glycolysis during ischemia
      by buffering H+ results in improved preservation of the hypertrophied heart, we
      studied the effect of a histidine-containing solution (HBS) on recovery of
      contractile function and energetic state. Hypertrophied rabbit hearts (aortic
      banding at 10 days) were subjected to 40 minutes of 37 degrees C ischemia and
      reperfusion in an isolated Langendorff model. This group was compared with groups
      receiving St Thomas solution and high-potassium Krebs buffer solution (KCl).
      Although both phosphocreatine (PCr) and ATP were lower in hypertrophied hearts by
      end-ischemia compared with nonhypertrophied age-matched controls, there was
      significantly higher PCr, ATP, and intracellular pH in the HBS group compared
      with the St Thomas and KCl groups. Recovery of left ventricular developed
      pressure was best in the HBS group (91% of preischemic values) as was end
      diastolic pressure after 30 minutes of reperfusion. Lactate production was also
      significantly greater in the HBS group, suggesting augmentation of anaerobic
      glycolysis. CONCLUSIONS: We concluded that administration of histidine-containing
      cardioplegia promotes anaerobic glycolysis and improves recovery of high-energy
      phosphates and contractile function in hypertrophied myocardium.

PMID- 7586442
TI  - Drug-induced heat-shock preconditioning improves postischemic ventricular
      recovery after cardiopulmonary bypass.
AB  - BACKGROUND: Heat-stress preconditioning of mammalian heart has been found to
      confer protection against ischemic reperfusion injury. Heat shock is generally
      provided by warming the animal by mechanical means, which is often impractical in
      a clinical setting. Amphetamine, a sympathomimetic drug, can elevate the body
      temperature as a result of enhanced endogenous lipolysis. In this study, we
      examined the effects of heat shock induced by amphetamine on postischemic
      myocardial recovery in a setting of coronary revascularization for acute
      myocardial infarction. METHODS AND RESULTS: Adult Yorkshire swine were injected
      with amphetamine (3 mg/kg IM) (n = 12), and body temperature was continuously
      monitored. For control studies, the pigs were injected with saline (n = 12). Five
      swine in each group were killed after 3 hours to obtain biopsies of vital organs
      to measure heat-shock protein (HSP) mRNAs. After 40 hours, the remaining 7 pigs
      in each group were placed on cardiopulmonary bypass, and the isolated, in situ
      heart preparations were subjected to 1 hour of occlusion of the left anterior
      descending coronary artery followed by 1 hour of global hypothermic cardioplegic
      arrest and 1 hour of reperfusion. Postischemic myocardial performance was
      monitored by measuring left ventricular (LV) pressure, its dP/dt, myocardial
      segment shortening, and coronary blood flow. Cellular injury was examined by
      measurement of creatine kinase release. The antioxidant enzymes superoxide
      dismutase and catalase were also assayed. Amphetamine treatment was associated
      with the induction of mRNAs for HSP 27, HSP 70, and HSP 89 in all the vital
      organs, including heart, lung, liver, kidney, and brain. Amphetamine also
      enhanced superoxide dismutase and catalase activities in the heart. Significantly
      greater recovery of LV contractile functions was noticed, as demonstrated by
      improved recovery of LV developed pressure (61% versus 52%), LV dP/dtmax (52%
      versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine
      kinase release in the amphetamine group. CONCLUSIONS: The results demonstrate
      that amphetamine can induce whole-body heat shock that can precondition the
      heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine
      is a sympathomimetic drug that may be used for preconditioning.

PMID- 7586446
TI  - Magnesium cardioplegia enhances mRNA levels and the maximal velocity of
      cytochrome oxidase I in the senescent myocardium during global ischemia.
AB  - BACKGROUND: The aged myocardium accumulates significantly more cytosolic calcium
      [Ca2+]i during ischemia, and functional recovery is more severely compromised as
      compared with the mature heart. Cardioplegia ameliorates these phenomena. The
      mechanism by which increased calcium accumulation reduces functional recovery in
      the senescent myocardium is unknown, but it has been suggested that futile
      calcium cycling in the mitochondria leading to depletion of ATP stores during
      normothermic global ischemia may be involved. METHODS AND RESULTS: To investigate
      the effect of cardioplegia on mitochondrial calcium ([Ca2+]mt) accumulation and
      the expression of cytochrome oxidase I (COX I) during global ischemia,
      mitochondria were isolated from mature (age, 15 to 20 weeks) and aged (age > 130
      weeks) rabbit hearts after Langendorff perfusion. Five perfused heart groups were
      investigated: 30 minutes of global ischemia without treatment (control), with
      potassium (K, 20 mmol/L), magnesium (Mg, 20 mmol/L), or potassium and magnesium
      (K/Mg) cardioplegia. No significant difference in [Ca2+]mt was evident in mature
      hearts with any protocol. In aged hearts, [Ca2+]mt was increased in global
      ischemia but was ameliorated with Mg and K/Mg cardioplegia. COX I mRNA levels in
      aged hearts were lower in both control and global ischemia but were increased
      with cardioplegia. Maximal velocities for COX I were significantly increased with
      Mg cardioplegia both in the mature and the aged myocardium. CONCLUSIONS: K and/or
      Mg cardioplegia ameliorates [Ca2+]mt accumulation in aged hearts during
      normothermic global ischemia and increases COX I mRNA levels to a level not
      significantly different from that found in mature hearts.

PMID- 7586447
TI  - Supplement of nitric oxide attenuates neutrophil-mediated reperfusion injury.
AB  - BACKGROUND: Nitric oxide (NO) derived from the endothelial cell has been
      identified as a constitutive chemical mediator that regulates the function of the
      endothelial cell in association with neutrophil (PMN) adhesion and activation.
      However, its role in the pathogenesis of myocardial reperfusion injury is not
      clear. METHODS AND RESULTS: Fifteen isolated rat hearts were perfused with
      modified Krebs-Henseleit solution and subjected to 20 minutes of global and
      normothermic ischemia. Then the hearts were reperfused for 45 minutes with
      different protocols: the control (C) group was reperfused without PMNs, the P
      group was reperfused with PMNs, and the N group was reperfused with PMNs and
      nitroprusside (10(-5) mol/L). The ozone chemiluminescence method was used for
      direct measurement of NO in the coronary effluent during reperfusion. NO in the
      coronary effluent in the C group decreased at reperfusion after normoxic
      perfusion, and this decrease in NO continued for the first 15 minutes of
      reperfusion. Percentage recovery of left ventricular developed pressure and
      coronary flow was significantly lower in the P group than that in the N group.
      Also, the N group had a significantly lesser Luminol-elicited chemiluminescence
      of the coronary effluent and ratio of PMN adherence to myocardial vasculature
      compared with the P group. CONCLUSIONS: This study demonstrated directly the
      decrease in NO production during reperfusion and showed that supplement of NO
      with NO donor attenuated the injury in which PMNs were involved. The results
      suggest that NO plays a significant role in reperfusion injury and that
      supplement of NO during reperfusion appears to be useful to attenuate this
      injury.

PMID- 7586449
TI  - Isoflurane attenuates cAMP-mediated vasodilation in rat microvessels.
AB  - BACKGROUND: Endothelium-dependent vasodilation mediated by cGMP is known to be
      attenuated by the inhalational anesthetic isoflurane. The present study examines
      the effect of isoflurane on beta-adrenergic and cAMP-mediated vasodilation.
      METHODS AND RESULTS: Fifty-three subepicardial coronary arteries (diameter, 103
      +/- 13 microns) from Wistar rats were studied in vitro in a pressurized (40 mm
      Hg), no-flow state with use of optical density video detection system. After
      preconstriction of vessels with the thromboxane A2 analogue U46619 10(-6) mol/L,
      concentration response curves to the nonselective beta-adrenergic agonist
      isoproterenol, the Gs protein activator sodium fluoride, the adenylate cyclase
      activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase
      inhibitor RO20-1724 were obtained either in the presence of absence (control) of
      2% isoflurane. Relaxations to all the agents tested were significantly reduced in
      the presence of isoflurane compared with controls. CONCLUSIONS: Isoflurane
      attenuates cAMP-mediated vasodilation. The impairment appears to be distal to
      adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.

PMID- 7586448
TI  - Improved 4- and 6-hour myocardial preservation by hypoxic preconditioning.
AB  - BACKGROUND: A brief hypoxic episode can precondition myocardium against a
      subsequent ischemic-reperfusion injury. The present study sought to determine
      whether intracellular ionic alterations, induced expression of heat-shock
      proteins (hsps), and/or catalase are involved in the cellular mechanisms by which
      hypoxic preconditioning can preserve postischemic function in a model of
      prolonged hypothermic storage. METHODS AND RESULTS: Two groups of isolated
      working rat hearts were studied: control (CON) and hypoxically preconditioned
      (HP) hearts. Hearts were arrested at 4 degrees C with St Thomas' cardioplegic
      solution and immersion-stored for either a 4- or 6-hour period. Myocardial
      function (ie, heart rate, aortic flow, coronary flow, developed pressure, and its
      first derivative dP/dtmax) was determined at baseline, after preconditioning, and
      during reperfusion. At similar time points, myocardial [Na+]i, [K+]i, [Mg2+]i,
      and [Ca2+]i were measured using an atomic absorption spectrophotometer, and the
      induction of hsp 70 and catalase mRNAs was assayed using Northern blot analysis.
      After 4 and 6 hours of hypothermic storage, aortic flow, dP/dtmax, and [K+]i were
      increased, whereas [Na+]i and [Ca2+]i were decreased significantly in the HP
      group compared with the CON group. Steady state mRNA levels of catalase and hsp
      70 were increased from baseline levels only in the HP group, with a peak (2.8-
      and 2.4-fold versus baseline) after 4 hours of storage. CONCLUSIONS: Our results
      indicate that intracellular ionic alterations and upregulation of catalase and
      hsp 70 gene expression may contribute to the mechanisms underlying hypoxic
      preconditioning, leading to improved postischemic function during prolonged
      hypothermic storage of hearts.

PMID- 7586450
TI  - Ischemia-induced interleukin-8 release after human heart transplantation. A
      potential role for endothelial cells.
AB  - BACKGROUND: Interleukin-8 (IL-8) secreted from endothelial cells is a powerful
      neutrophil chemoattractant and activator. We hypothesized that human endothelial
      cells deprived of oxygen would secrete IL-8, which might translate into elevated
      IL-8 production after cardiac ischemia. Furthermore, we hypothesized that
      coronary sinus (CS) IL-8 levels would be particularly high after cardiac
      preservation for transplantation, due to extended ischemic times. METHODS AND
      RESULTS: Human saphenous vein endothelial cells exposed to a hypoxic environment
      (PO2 < 20 mm Hg) demonstrated a time-dependent release of IL-8 (measured by
      ELISA) into the culture supernatant as early as 4 hours after exposure. To
      determine whether cardiac preservation in humans was associated with IL-8
      production, we obtained CS blood samples 5 minutes after reperfusion in a
      consecutive series of patients after they underwent cardiac transplantation (CTX,
      n = 20) or elective cardiac surgery (non-CTX, n = 21). CTX patients demonstrated
      significantly higher CS IL-8 levels than non-CTX patients (325 +/- 123 versus 50
      +/- 17 ng/mL, respectively, P < .05). Further analysis of the CS samples revealed
      that a biochemical marker of myocyte injury (myoglobin) was similarly elevated in
      the CTX patients compared with the non-CTX patients (3340 +/- 625 versus 1151 +/-
      525 ng/mL, respectively, P < .05). CONCLUSIONS: These differences may reflect the
      longer ischemic times of CTX compared with non-CTX hearts (161 +/- 10 versus 80
      +/- 6 minutes, P < .0001) and suggest that the neutrophil
      chemoattractant/activator IL-8 may contribute to myocyte injury after prolonged
      hypothermic cardiac ischemia, as occurs during human cardiac transplantation.

PMID- 7586451
TI  - Direct effects of protamine sulfate on myocyte contractile processes. Cellular
      and molecular mechanisms.
AB  - BACKGROUND: Administration of the arginine-rich, highly charged protamine (PROT)
      molecule has been associated with episodes of acute left ventricular (LV)
      dysfunction. The objective of the present study was to test the hypothesis that
      PROT has direct effects on isolated LV myocyte contractile processes and
      sarcolemmal transduction systems. METHODS AND RESULTS: Exposure of porcine LV
      myocytes (n = 305) to 40 micrograms/mL PROT (reflecting a dose of 2.5 mg/kg)
      decreased basal contractile function and beta-adrenergic responsiveness. For
      example, myocyte percent shortening was 4.3 +/- 0.1% in control myocytes and
      decreased to 2.8 +/- 0.2% in the presence of 40 micrograms/mL PROT (P < .05).
      Myocyte percent shortening was 9.3 +/- 0.7% after beta-adrenergic receptor
      stimulation (isoproterenol; 25 nmol/L) and was significantly reduced in the
      presence of 40 micrograms/mL PROT (5.7 +/- 0.7%, P < .05). PROT reduced myocyte
      responsiveness to forskolin (100 mumol/L), which directly activates adenylate
      cyclase, by > 40% from forskolin. In addition, PROT abolished the inotropic
      effects of ouabain on myocyte contractile function. To determine contributory
      mechanisms for the effects of PROT on myocyte sarcolemmal systems, beta-receptor-
      and cardiac glycoside-binding characteristics were determined in sarcolemmal
      preparations. beta-receptor binding was 175 +/- 10 fmol/mg and was reduced to 140
      +/- 6 fmol/mg in the presence of PROT (P < .05). Ouabain receptor binding was 7.1
      pmol/mg and decreased to 2.6 +/- 0.4 pmol/mg in the presence of PROT. In
      addition, cAMP production after stimulation with isoproterenol and forskolin was
      significantly blunted in the presence of PROT. Variants of the PROT moelcule were
      constructed by specific amino acid substitutions and deletions, which provided a
      means to vary charge as well as structure. Substitution of arginine with lysine
      in the PROT peptide sequence ameliorated the negative effects on myocyte
      contractile processes; despite identical overall charge (21+). However, a PROT
      variant with an 18+ charge but different amino acid sequence induced significant
      negative effects on myocyte function and inotropic responsiveness. Thus, the
      effects of PROT on myocyte contractile processes are not due simply to the high
      positive charge of the molecule. To further establish that PROT can contribute to
      changes in LV function in the clinical setting, fluorescein-labeled PROT was
      circulated in antegradely perfused rabbit hearts. Microscopic examination
      revealed that PROT could traverse the vascular compartment of the myocardium and
      come in direct contact with the myocyte. CONCLUSIONS: The unique findings from
      the present study suggest that a fundamental contributory mechanisms for the
      changes in LV function observed after protamine administration may be the direct
      effect of unbound protamine on myocyte contractile processes.

PMID- 7586452
TI  - Does cardiopulmonary bypass alone elicit myoprotective preconditioning?
AB  - BACKGROUND: Brief episodes of ischemia can precondition myocardium. Ischemic
      preconditioning (PC) has been proposed as an adjuvant method of improving
      myocardial protection during cardiac surgery. It is unknown whether CPB without
      an episode of ischemia generates the PC response. METHODS AND RESULTS: To prove
      that PC occurs in sheep, groups 1 (non-CPB control) and 2 (non-CPB ischemic PC,
      three 5-minute episodes of normothermic regional ischemia) were studied. Groups 3
      (CPB alone), 4 (CPB-alpha receptor blockade, phentolamine 5 mg/kg), and 5 (CPB
      adenosine receptor blockade, 8-sulfophenyltheophylline 5 mg/kg) were placed on
      CPB for 30 minutes and subsequently weaned. All groups underwent 60 minutes of
      normothermic regional ischemia and 150 minutes of reperfusion. The area at risk
      (AR) was delineated by Monastryl blue pigment, whereas the infarct size (IS) was
      determine by tetrazolium staining. Body mass, left ventricular mass, and AR were
      not different between groups. Ischemic PC was demonstrated in this ovine model by
      a 54% reduction of IS relative to AR (group 1 versus group 2, P < .01). CPB alone
      produced a similar percentage IS reduction without ischemia (group 3 versus group
      1, P < .01) that was prevented by either alpha-adrenergic receptor (group 4
      versus group 3, P < .01) or adenosine receptor (group 5 versus group 3, P < .01)
      blockade. CONCLUSIONS: CPB alone appears sufficient to elicit the PC response
      important for myocardial protection during cardiac surgery. These data suggest
      that myocardial alpha-adrenergic receptor and adenosine receptor stimulation are
      involve in initiating CPB-induced PC.

PMID- 7586453
TI  - Right gastroepiploic-to-coronary artery bypass. The first decade of use.
AB  - BACKGROUND: The right gastroepiploic artery was first used by us as a coronary
      artery bypass graft (CABG) in June 1984 and has become an accepted alternative
      conduit for myocardial revascularization. METHODS AND RESULTS: We have now
      performed this operation in 126 patients (111 of whom were men) aged 32 to 78
      years. The right gastroepiploic artery was used as a pedicle graft to the right
      main coronary artery in 25 patients, to its posterior descending branch in 90, to
      a left ventricular branch in 2, to branches of the circumflex system in 6, and to
      the left anterior descending artery in 1. Free (aortocoronary) gastroepiploic
      grafts were placed to circumflex branches in 2 patients. There were 2 hospital
      deaths (stroke, arrhythmia), and mean +/- SD postoperative stay was 7.5 +/- 2.0
      days. All survivors were symptomatically improved and are functionally in New
      York Heart Association functional class I or II. There have been 3 late deaths
      (at 34, 50, and 84 months) in 2 to 120 months of follow-up (mean, 41.4 months).
      Angiography of bypass grafts and coronary arteries was performed in 44 patients
      at 7 days to 80 months postoperatively, providing direct evidence of
      gastroepiploic graft patency in 34 patients and strong indirect evidence in
      another 6; adequate data could not be obtained in 3 patients for technical
      reasons, and 1 graft was occluded. CONCLUSIONS: These short-term, intermediate,
      and long-term results demonstrate the suitability of the right gastroepiploic
      artery as a CABG. The use of the right gastroepiploic artery as a graft to
      coronary arteries on the posterior wall of the heart, in conjunction with one or
      both internal mammary arteries, has the potential to allow complete myocardial
      revascularization with viable arterial grafts.

PMID- 7586454
TI  - University of Wisconsin solution preserves myocardial calcium current response to
      isoproterenol in isolated canine ventricular myocytes.
AB  - BACKGROUND: University of Wisconsin (UW) solution has been shown to be an
      effective solution for cold storage of various organs. This study was designed to
      evaluate the subcellular protective mechanism of UW solution during cardiac
      myocyte storage using patch-clamp techniques for the first time as a tool for the
      detection of myocyte viability. METHODS AND RESULTS: The protective effects of UW
      solution on the preservation of dihydropyridine-sensitive Ca2+ channel current
      response to catecholamine were evaluated in canine cardiac ventricular cells by
      measurement of single channel open probability. Single ventricular myocytes were
      isolated and stored in UW solution, in Stanford (SF) solution, or in St Thomas'
      (ST) solution at 4 degrees C for 2, 6, 12, and 24 hours, and after each storage
      period, recordings were made of cell-attached single Ca2+ channel currents. When
      0.1 mumol/L isoproterenol was applied, percent mean open probability of the Ca2+
      channel tested in freshly isolated cells was 167 +/- 4% (n = 24) of controls
      (100%). The response was decrescent with increased duration of the hypothermic
      storage and was only 130 +/- 12% (n = 4) after 24 hours of storage in SF solution
      and 135 +/- 9% (n = 7) in ST solution. However, it was significantly highly
      preserved as much as 165 +/- 9% (n = 6) in UW solution. Ca2+ channel kinetics and
      channel conductance were not changed after up to 24 hours of hypothermic storage.
      CONCLUSIONS: Hypothermic storage of canine cardiac myocytes in UW solution
      preserved beta-adrenergic response, which suggests that UW solution during cold
      storage preserved high-energy phosphates in myocytes that are responsible for
      Ca2+ channel phosphorylations.

PMID- 7586455
TI  - Left ventricular function, twist, and recoil after mitral valve replacement.
AB  - BACKGROUND: Preservation of the mitral subvalvular apparatus during mitral valve
      replacement (MVR) has become more popular, in part because of the clinically and
      experimentally demonstrated more optimal left ventricular (LV) performance after
      surgery; the mechanisms responsible for this beneficial influence, however, have
      not been clearly elucidated. METHODS AND RESULTS: Fourteen dogs underwent
      placement of 26 myocardial markers into the LV and septum. One week later, the
      animals were studied while awake, sedated, and atrially paced (120 beats per
      minute) both under baseline conditions and after inotropic stimulation (calcium).
      The animals then underwent MVR and were randomized into either chord-sparing (MVR
      Intact) or chord-severing (MVR-Cut) techniques. Two weeks later, the animals were
      studied under the same conditions. LV systolic function was assessed by the slope
      of the end-systolic pressure-volume relation (Ees); early LV diastolic filling
      was analyzed by the pressure-time constant of relaxation (tau). The instantaneous
      longitudinal gradient of torsional deformation for the LV (twist) was also
      calculated, as were the changes in twist with respect to time during systole and
      early diastole (LV recoil). Intergroup comparison showed a trend toward increased
      contractility (Ees, P = .061, before versus after MVR), as well as faster
      relaxation for the MVR-Intact group. Concurrent analysis of LV systolic function
      and the rate of systolic twist revealed a significant inverse relation, which
      disappeared after MVR when the chordae were severed. CONCLUSIONS: These
      observations suggest that the mitral subvalvular apparatus acts as a modulator of
      LV systolic torsional deformation into LV pump (or ejection) performance.

PMID- 7586456
TI  - Creation of a controlled venoarterial shunt. A surgical intervention for right
      side circulatory failure.
AB  - BACKGROUND: Right-side circulatory failure (RSCF), a common complication of heart
      transplant and left ventricular assist device recipients, results in decreased
      cardiac output because of diminished flow across the pulmonary circuit. We
      hypothesized that creation of a controlled venoarterial shunt would result in
      decompression of the right ventricle and improved systemic cardiac output at
      tolerable oxygen saturations. METHODS AND RESULTS: A venoarterial shunt was
      created in a large-animal model (calf, n = 6). RSCF was induced by banding the
      pulmonary artery. Hemodynamic measures and blood gas determinations were obtained
      during nonshunted and shunted states. Pulmonary artery banding increased mean
      right ventricular systolic pressure from 44.9 +/- 2.1 mm Hg (mean +/- SEM) to
      85.9 +/- 6.9 mm Hg (P < .05, paired t test) and decreased mean aortic flow from
      7.8 +/- 1.0 to 4.2 +/- 1.1 L/min (P < .05). Flow through a venoarterial shunt at
      approximately 40% of cardiac output resulted in a decrease in right ventricular
      end-systolic pressure from 85.9 +/- 6.9 to 72.1 +/- 5.6 mm Hg (P < .01, ANOVA), a
      decrease in mean pulmonary artery pressure from 42.9 +/- 5.0 to 37.2 +/- 3.8 mm
      Hg (P < .01), and an increase in aortic flow from 4.2 +/- .05 to 5.1 L/min (P <
      .01). Left ventricular stroke work decreased from 2.22 +/- 0.28 to 1.55 +/- 0.88
      (P < .05). Carotid artery oxygen saturation did not change significantly (99.9 +/
      .02 to 97.6 +/- 1.7) during shunting. CONCLUSIONS: A controlled venoarterial
      shunt improved hemodynamics and cardiac output in a large animal model with RSCF.
      This strategy may be useful in the management of transplant and left ventricular
      assist device recipients with perioperative RSCF.

PMID- 7586458
TI  - Efficiency of in vivo gene transfection into transplanted rat heart by coronary
      infusion of HVJ liposome.
AB  - BACKGROUND: Current methods of in vivo gene transfer into myocardium are limited
      by low efficiency. To improve in vivo gene transfer, a gene transfer method using
      hemagglutinating virus of Japan (HVJ) as a viral vector can be an alternative.
      METHODS AND RESULTS: In vivo gene transfection of FITC-labeled oligonucleotide (F
      ODN) and cDNA of beta-galactosidase (beta-gal) was examined with use of the HVJ
      liposome (H group) or without it (C group). In the H group, F-ODN or cDNA of beta
      gal were complexed with liposomes, DNA binding nuclear protein (HMG1), and the
      viral protein coat of HVJ. After the harvest of donor rat hearts arrested by
      cardioplegia, the coronary artery was infused with the liposome gene complex. The
      hearts were transplanted into the abdomens of recipient rats and harvested 3 days
      after transplantation. Regarding F-ODN, the H group clearly showed FITC staining
      in the nuclei of the myocytes and endothelial cells in almost all layers of the
      myocardium as compared with the C group. Regarding the expression of beta-gal,
      the H group showed a clear expression of beta-gal on myocytes, whereas very low
      expression of beta-gal was seen in the C group. CONCLUSIONS: The donor hearts
      were transfected with F-ODN and beta-gal gene in almost all layers of the
      myocardium as a result of coronary infusion of the HVJ liposome during
      cardioplegic arrest. Our method is seen as a novel in vivo gene transfer
      technique for the heart and may provide a new tool for both research and therapy
      of heart transplantation.

PMID- 7586460
TI  - Effects of aortopulmonary collaterals on cerebral cooling and cerebral metabolic
      recovery after circulatory arrest.
AB  - BACKGROUND: Aortopulmonary collaterals (APC) have been associated with an
      increased risk of choreoathetosis after deep hypothermic circulatory arrest
      (DHCA). To study the effects of APC on cerebral hemodynamics and metabolism
      before and after DHCA, a piglet model was developed. METHODS AND RESULTS:
      Protocol 1: Eight 4- to 6-week-old piglets underwent placement of a left
      subclavian-to-main pulmonary artery shunt. Control shunts (n = 4) were ligated,
      APC shunts (n = 4) were left patent. All animals were placed on cardiopulmonary
      bypass (CPB) and cooled in identical fashion for 20 minutes. Temperature probes
      were placed in the nasopharynx, cortex, and deep brain. Control animals achieved
      significantly lower temperatures in all three areas by the end of cooling (17.5
      degrees C versus 20.1 degrees C, 19.0 degrees C versus 22.3 degrees C, and 17.5
      degrees C versus 21.0 degrees C, respectively, P < .005). Protocol 2: Six control
      and six APC animals were instrumented as described. All were placed on CPB,
      cooled to 18 degrees C, arrested for 90 minutes, and rewarmed to 37 degrees C.
      Cerebral blood flow (CBF) was measured with radioactive microspheres while warm
      on CPB, after cooling, and after rewarming. Arterial and sagittal sinus blood
      gases and CBF were used to calculate the cerebral metabolic rate of oxygen
      consumption (CMRO2). Both CBF and CMRO2 were significantly higher after rewarming
      to 37 degrees C in control versus APC animals (28 +/- 3 versus 14 +/- 2 mL/100 g
      per minute and 1.72 +/- 0.21 versus 1.04 +/- 0.14 mL O2/100 g per minute,
      respectively, P < .05). CONCLUSIONS: APC decrease the rate of cerebral cooling on
      CPB and even if temperature is controlled result in increased cerebral metabolic
      derangement after DHCA. Patients with such collaterals may need additional
      measures to optimize cerebral protection.

PMID- 7586457
TI  - Myocardial beta-adrenergic receptor function and high-energy phosphates in brain
      death--related cardiac dysfunction.
AB  - BACKGROUND: Cardiac failure remains an important problem after heart
      transplantation and may be associated with events that occur during brain death
      (BD) before transplantation. In this study, cardiac function is studied after BD,
      and biochemical evaluation of myocardial high-energy phosphates and the beta
      adrenergic receptor system is presented. METHODS AND RESULTS: The hearts of 17
      mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers,
      and ultrasonic dimension transducers to measure ventricular pressure and volume
      relationships. In a validated canine BD model, systolic right and left
      ventricular (RV/LV) function was analyzed by load-insensitive measurements during
      caval occlusion (preload-recruitable stroke work, PRSW). The beta-adrenergic
      receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and
      creatine phosphate (CP) were measured before and 6 to 7 hours after BD. Results
      are expressed as mean +/- SEM (*P < .05 versus baseline, paired two-tailed
      Student's t test). Myocardial function deteriorated significantly from baseline
      PRSW (RV, 22 +/- 1 erg x 10(3); LV, 75 +/- 4 erg x 10(3)) by 37 +/- 10% for the
      RV (P < .001) and 22 +/- 7% for the LV (P < .001). BAR density increased from 282
      +/- 42 to 568 +/- 173 fmol/mg for the RV and from 291 +/- 64 to 353 +/- 56
      fmol/mg for the LV. Isoproterenol-stimulated AC activity was also significantly
      enhanced after BD. ATP and CP, however, remained unchanged after BD compared with
      baseline values before BD. CONCLUSIONS: BD causes significant systolic
      biventricular dysfunction. The loss of ventricular function after BD was more
      prominent in the right ventricle and may contribute to early postoperative RV
      failure in the recipient. These injuries occurred despite BAR system upregulation
      after BD. Global myocardial ischemia is unlikely, since ATP and CP remained
      normal before and after BD.

PMID- 7586459
TI  - Clenbuterol induces hypertrophy of the latissimus dorsi muscle and heart in the
      rat with molecular and phenotypic changes.
AB  - BACKGROUND: Skeletal muscle assistance of the circulation for patients in end
      stage heart failure requires electrical training of the latissimus dorsi flap to
      produce fatigue resistance. This process of electrical transformation and the
      development of postmobilization atrophy results in a profound loss in peak power
      generated. The beta 2-adrenoceptor agonist clenbuterol was used to investigate
      its potential to selectively induce skeletal muscle hypertrophy, particularly the
      latissimus dorsi muscle (LDM), independent of adverse effects on cardiac muscle.
      METHODS AND RESULTS: Forty-one male Sprague-Dawley rats were divided into four
      groups and used in this study. Clenbuterol 2 micrograms.g body wt-1.d-1 was
      administered subcutaneously for a period of either 5 weeks (group A) or 2 weeks
      (group A1). Groups B and B1 (controls) were injected with 0.5 mL normal saline
      once daily. At the end of the experimental period, all rats were weighed and
      terminally anesthetized for removal of the left LDM, left gastrocnemius-plantaris
      soleus (GPS) muscles, and heart. The results showed that the increase in body
      weight did not differ significantly between the clenbuterol-treated and control
      groups (P > .5). The ratio of LDM to tibial length (hypertrophic index) for
      groups A and A1 was significantly greater than controls (P < .01), which
      represented a 20% to 29% increase. The hypertrophy was more pronounced for
      hindlimb skeletal muscle (21% to 35% for GPS), and the effects of this relatively
      high dose of clenbuterol on the heart were less marked (18% to 20% hypertrophy).
      RNA analyses indicate that ventricles of clenbuterol-treated rats express
      elevated levels of mRNA to atrial natriuretic factor without a concomitant
      increase in skeletal alpha-actin and beta-myosin heavy chain, consistent with a
      "physiological" form of cardiac hypertrophy. CONCLUSIONS: Clenbuterol induces
      significant hypertrophy of the LDM associated with specific changes in cardiac
      gene expression.

PMID- 7586461
TI  - In-hospital and long-term outcome after reoperative coronary artery bypass graft
      surgery.
AB  - BACKGROUND: Increasingly over the past several years, patients have returned
      after coronary surgery for reoperative procedures, and the experience has become
      substantial. In this report, we describe immediate- and long-term outcomes after
      reoperative coronary artery bypass graft surgery. METHODS AND RESULTS: The source
      of data was the clinical database at Emory University. The surgical procedure and
      statistical methods were standard. Data were collected prospectively and entered
      into a computerized database. Follow-up was by letter, telephone, or hospital
      records documenting additional events resulting in readmission. In-hospital
      correlates of survival were determined by logistic regression, and long-term
      correlates were determined by Cox model analysis. There were 2030 patients with a
      mean age of 61 and a mean of 7.8 +/- 4.1 years since the first surgery. The mean
      ejection fraction was close to 50%, and the majority had three-vessel or left
      main disease. Urgent or emergency surgery was required in 16.6%. The internal
      mammary was used in 60.1%. Q-wave myocardial infarctions occurred in just over
      5%. Neurological events increased from 1.2% at less than age 50 to 4.1% at more
      than age 70. The hospital mortality increased from 5.7% at less than age 50 to
      10% at more than age 70, with an overall rate of 7.0%. Mortality was 5.7% for
      elective, 10.9% for urgent, and 16.4% for emergency cases. Angina was noted at
      follow-up in 41.3%. Urgent or emergency surgery, reduced ejection fraction,
      hypertension, older age, and female sex were univariate and multivariate
      correlates of in-hospital death. Diabetes was a univariate correlate only. Five-
      and 10-year survival rates were 76% and 55%, respectively. Five- and 10-year
      myocardial infarction-free survival rates were 63% and 40%, respectively. By 12
      years, few patients were free of cardiac events. The univariate and multivariate
      correlates of long-term mortality were older age, reduced ejection fraction,
      hypertension, diseased vessels, presence of diabetes, congestive failure, and
      emergency surgery, with a strong trend for female sex. The use of the internal
      mammary artery was not a correlate for long-term mortality. CONCLUSIONS: Patients
      undergoing reoperative procedures have higher mortality initially and at long
      term than patients undergoing a first procedure. Expected mortality based on
      covariates may help in the decision of whether to perform reoperative coronary
      artery bypass graft surgery.

PMID- 7586462
TI  - Myocardial revascularization with laser. Preliminary findings.
AB  - BACKGROUND: We assessed the transmyocardial laser revascularization (TMLR) as
      sole therapy in patients with symptomatic coronary artery disease refractory to
      interventional or medical treatment. METHODS AND RESULTS: Thirty-one patients
      were evaluated with positron emission tomography (PET), dobutamine
      echocardiography, 201Tl single-photon emission computed tomography (201Tl-SPECT),
      and multigated acquisition radionuclide ventriculography (MUGA). TMLR was
      performed in 21 patients who had demonstrable ischemia in viable myocardium. The
      mean Canadian Cardiovascular Society (CCS) angina class was 3.70 +/- 0.7 (4
      patients with unstable angina). Untreated septal segments were used as controls.
      At 3 months, (n = 15 patients), the mean CCS angina class was to 2.43 +/- 0.9 (P
      < .05). On dobutamine echocardiography, the mean resting wall motion score index
      was improved by 16% in lased segments (P < .03 vs control), and mean LVEF at peak
      stress increased by 19% (P = NS vs baseline). On 201Tl-SPECT, perfusion of lased
      and nonlased segments did not change. On PET, the mean ratio of subendocardial to
      subepicardial perfusion (SEn/SEp) increased 14% over baseline (P < .001 vs
      control). At 6 months (n = 15 patients), the mean CCS angina class was 1.7 +/-
      0.8 (P < .05). The mean resting wall motion score index was up by 13% in lased
      segments (P < .05 vs control). Resting LVEF was unchanged. Stress LVEF increased
      21% (P = NS vs baseline). Myocardial perfusion remained unchanged by 201Tl-SPECT.
      On PET, 36% of the lased segments were better, and 25% were worse compared with
      baseline. The resting SEn/SEp by PET was up 21% (P < .001 vs control). All deaths
      (two perioperative and three late) occurred in patients with preoperative
      congestive heart failure. Two patients required repeat revascularization of new
      coronary lesions. CONCLUSIONS: These results suggest that TMLR improves anginal
      status, relative endocardial perfusion, and cardiac function in patients who do
      not have preoperative congestive heart failure.

PMID- 7586464
TI  - Enrollment in the Health Alliance Plan HMO is not an independent risk factor for
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Henry Ford Hospital is the sole provider of cardiac surgical services
      for the Health Alliance Plan, a health maintenance organization (HMO) that
      presently serves 450,000 enrollees. METHODS AND RESULTS: To determine the effect
      of managed care referral patterns on the outcome of coronary artery bypass graft
      (CABG) surgery, we retrospectively reviewed two concurrent groups of patients,
      569 HMO patients and 225 patients with free-for-service (FFS) insurance, who had
      undergone isolated primary CABG surgery between January 1, 1990 and January 31,
      1994. The 605 patients with Medicare operated on during the same time frame were
      excluded to obviate age bias. Age, sex, use of cardiac medications, history of
      prior percutaneous transluminal coronary angioplasty or thrombolytic therapy,
      history of recent and remote myocardial infarction, extent of coronary disease,
      presence of preexisting comorbid conditions, and incidence of unstable clinical
      syndromes and left ventricular dysfunction (ejection fraction < 40%) were
      comparable for both groups. In hospital mortality (HMO group, 1.9%; FFS group,
      2.2%), mean ICU stay (HMO, 2.6 +/- 0.3 days; FFS, 2.3 +/- 0.3 days), and total
      hospital length of stay (HMO, 9.8 +/- 0.8 days; FFS, 8.6 +/- 0.6 days) were
      likewise similar. CONCLUSIONS: These data refute the notion that the gate-keeper
      mentality often associated with managed-care health insurance vehicles results in
      delayed referral of patients with coronary artery disease and results in
      suboptimal outcome.

PMID- 7586463
TI  - Optimal timing of coronary artery bypass graft surgery after acute myocardial
      infarction.
AB  - BACKGROUND: To assess optimal timing for coronary artery bypass graft surgery
      (CABG) after an acute myocardial infarction (AMI), all patients undergoing CABG
      without associated procedures at our institution from January 1, 1991, to July
      30, 1992, were reviewed. Patients were divided into three groups based on time
      from infarct to revascularization. The control group consisted of patients
      operated on for angina refractory to medical management. Relative risks (incident
      infarction group divided by incident control group) were established for need of
      vasopressors, new balloon to separate from bypass, perioperative myocardial
      infarction, and hospital mortality. METHODS AND RESULTS: One hundred sixteen
      patients underwent CABG within 6 weeks of infarction. In the experimental group,
      58 patients underwent CABG for non-Q-wave infarction, and 58 patients underwent
      CABG for Q-wave infarction. In the control group, 255 patients underwent surgery
      for angina without infarction. Patients were analyzed by group relative to the
      time between infarction and CABG. Patients were analyzed between infarction and
      CABG and assigned to one of three groups. Group 1 patients were revascularized
      within 48 hours; group 2, between 3 and 5 days; and group 3, after 5 days.
      Significance was determined by Fisher's exact or Mantel-Haenszel chi 2 test where
      appropriate. Multivariate analysis was performed on statistics that were
      significant. All patients within all groups after Q-wave or non-Q-wave myocardial
      infarction had a significantly higher risk of needing an intra-aortic balloon
      pump and vasopressors to be weaned from bypass and a greater incidence of
      perioperative MI compared with control patients. Surgical mortality is highest
      immediately after Q-wave infarctions. CONCLUSIONS: Patients with non-Q-wave
      infarction may undergo CABG relatively safely at any time. Acceptable timing for
      CABG after Q-wave infarction is after 48 hours.

PMID- 7586465
TI  - Results of revascularization in patients with severe left ventricular
      dysfunction.
AB  - BACKGROUND: In patients with coronary artery disease and poor ventricular
      function (ejection fraction, < 20%), bypass grafting remains a surgical
      challenge. This study evaluates experience with isolated revascularization in
      such patients. METHODS AND RESULTS: In 79 consecutive patients (69 men, 10 women;
      average age, 59 +/- 9 years), preoperative ejection fraction was 18 +/- 5%.
      Indications for surgery were congestive heart failure (CHF) in 5 of 79 patients
      (6%), CHF and angina in 19 (24%), angina in 41 (52%), ventricular arrhythmias
      (VAs) in 8 (10%), and critical anatomy in 6 (8%). Some patients had prior VAs (23
      of 79; 29%) or mitral regurgitation (18; 23%) and required emergent surgery (25;
      32%). At surgery, temperature mapping ensured adequate distribution of antegrade
      cold cardioplegia, with 3.6 +/- 0.7 grafts per patient, including left internal
      mammary artery graft in 60 of 79 (76%) and endarterectomy in 14 (18%). Hospital
      mortality was 3.8%. Perioperative support included intra-aortic balloon pump in
      18 of 79 (23%) and drugs for VAs in 28 (35%). Morbidity included myocardial
      infarction in 2 of 79 (2.5%) and stroke in 2 (2.5%). During follow-up, there were
      19 late deaths. Actuarial survival was 94%, 82%, and 68% at 1, 2, and 5 years,
      respectively, and was similar in patients with severe angina, CHF, mitral
      regurgitation, or VAs. Freedom from sudden death was 100%, 98%, and 91% at 1, 2,
      and 5 years, respectively. Among survivors, angina improved in 84% and heart
      failure improved in 26%. CONCLUSIONS: These data support bypass graft surgery in
      patients with severe LV dysfunction. With careful cardioplegic techniques,
      hospital mortality was low (3.8%). Long-term survival is encouraging, with good
      relief of symptoms in most patients. Perioperative VAs are frequent but respond
      to medical treatment, with only 23% of patients discharged on antiarrhythmic
      drugs. Five-year freedom from sudden death is 91%, with only 3 late sudden deaths
      in this series.

PMID- 7586466
TI  - Unilateral versus bilateral internal mammary revascularization. Survival and
      event-free performance.
AB  - BACKGROUND: The influence of unilateral (UL) and bilateral (BL) mammary artery
      revascularization, within age groups < or = 60 years and > 60 years, on patient
      survival, ischemic-related events, and interventional management was studied in
      1142 patients who had coronary artery bypass graft surgery between 1984 and 1992.
      METHODS AND RESULTS: UL revascularization was performed in 765 (67%) and BL in
      377 (33%) patients with supplemental vein grafts. The overall early and hospital
      mortality rate was 2.7%. For UL in the age group < or = 60 years, it was 1.1%;
      for BL < or = 60 years, 1.3% (P = NS); for UL > 60 years, 4.3%; and for BL > 60
      years, 2.8% (P = NS). Twenty-five preoperative patient characteristics
      representing demographics, extent of disease, concomitant disease, ventricular
      dysfunction, previous surgery, and status did not differentiate the patient
      groups (P = NS). Patient survival at 5 years was not different: 94% for UL < or =
      60 years, 95% for BL < or = 60 years, 91% for UL > 60 years, and 86% for BL > 60
      years (P = NS). The freedom from ischemic-related events was not different at 5
      years (P = NS). The freedom from recurrent angina was 78% for UL < or = 60 years,
      88% for BL < or = 60 years, 82% for UL > 60 years, and 83% for BL > 60 years (P =
      NS). The myocardial infarction freedom was 98% for UL < or = 60 years, 96% for BL
      < or = 60 years, 99% for UL > 60 years, and 97% for BL > 60 years (P = NS). The
      freedom from sudden unexpected death and cardiac death did not differentiate the
      groups (P = NS). The freedom from angioplasty and reoperation did not
      differentiate the groups (P = NS). The freedom from all ischemic-related and
      interventional events was 76% for UL < or = 60 years, 84% for BL < or = 60 years,
      81% for UL > 60 years, and 79% for BL > 60 years (P = NS). A trend exists for
      less angina pectoris in the bilateral population < or = 60 years, which reflects
      in the trend in the freedom from overall events. CONCLUSIONS: UL and BL mammary
      artery revascularizations have the same early mortality regardless of age but do
      not reveal any advantage for BL revascularization at 5 to 7 years.

PMID- 7586467
TI  - Is sex a factor in determining operative risk for aortocoronary bypass graft
      surgery?
AB  - BACKGROUND: This study examines trends and sex differences in characteristics of
      patients referred for bypass graft surgery to identify factors associated with
      operative morbidity and mortality. METHODS AND RESULTS: Data were collected
      prospectively on consecutive patients (1132 men and 355 women). Over time, the
      proportion of patients > 65 years old, with diabetes, or requiring urgent
      surgery, increased. Predictors of mortality were age > 75 years, urgent surgery,
      and poor left ventricular (LV) grade. Women were older (62 +/- 9 versus 59 +/- 9
      years, P < .001) and had more varicose veins (18% versus 7%, P < .001), diabetes
      (27% versus 18%, P < .001), hypertension (48% versus 41%, P < .05), peripheral
      vascular disease (16% versus 12%, P < .05), and more severe angina (P < .001).
      There were no sex differences in prior myocardial infarction (59% versus 62%) or
      need for urgent surgery (17% versus 18%). Women had a higher ejection fraction
      (51% +/- 12% versus 47% +/- 14%, P < .001) and fewer diseased vessels (2.4 +/-
      0.7 versus 2.6 +/- 0.6, P < .001) and received fewer grafts (2.9 +/- 0.9 versus
      3.3 +/- 0.8, P < .001). Women had smaller body size but were no more likely to
      have small target vessels (< 1.5 mm). There was no sex difference in operative
      mortality (1.4% versus 1.1%), perioperative myocardial infarction (4.8% versus
      3.5%), need for intra-aortic balloon pump (10% versus 8%), stroke (1.7% versus
      1.4%), reexploration for bleeding (1.7% versus 1.7%), or leg infection (2.0%
      versus 1.4%). Women had fewer sternal wound infections (0.6% versus 2.2%, P <
      .05). CONCLUSIONS: Predictors of mortality include advanced age, decreased LV
      function, and need for urgent surgery. With time, despite increasing age,
      associated diabetes, and increased urgent surgery, operative mortality has
      decreased. Women were older and had more diabetes and hypertension but less
      extensive disease and better LV function. Bypass graft surgery was associated
      with equally low mortality in women and men (1.4% versus 1.1%). Concern over
      increased operative mortality in women should not bias referral patterns for
      angiography and coronary bypass graft surgery.

PMID- 7586468
TI  - Outcomes of coronary artery bypass graft surgery in 24,461 patients aged 80 years
      or older.
AB  - BACKGROUND: Coronary artery bypass graft surgery is increasingly common in
      patients of age > or = 80 years. Single-institution reviews have cited a wide
      range of mortality results after bypass surgery in this age group, in part
      because of limited sample sizes. Using claims data, we examined recent national
      trends in the use and outcomes of bypass surgery in the very elderly. METHODS AND
      RESULTS: From an examination of Medicare data from 1987 through 1990, we
      identified 24,461 patients of age > or = 80 years who underwent bypass surgery.
      We compared surgical outcomes in these patients with those in Medicare patients
      of age 65 to 70 years. We found that the national use of bypass surgery in
      patients of age > or = 80 years increased 67% between 1987 and 1990. Compared
      with patients of age 65 to 70 years, the very elderly had significantly longer
      postoperative hospital stays (mean, 14.3 versus 10.4 days), higher charges (mean,
      $48,200 versus $38,000), and greater costs (mean, $27,200 versus $21,700). In
      hospital (11.5% versus 4.4%), 1-year (19.3% versus 7.9%), and 3-year mortality
      rates (28.8% versus 13.1%) after bypass surgery were also significantly higher in
      patients of age > or = 80 years compared with younger patients. Although their
      initial surgical risk was high, octogenarians who underwent bypass surgery had a
      long-term survival rate similar to that of the general US octogenarian
      population. CONCLUSIONS: The use of bypass surgery in patients of age > or = 80
      years in increasing. These very elderly patients face high surgical risks and
      accumulate significant hospital expenses. Further research is indicated to
      determine whether the long-term benefits from bypass surgery in the very elderly
      outweigh the increased procedural risks.

PMID- 7586470
TI  - Endoventricular remodeling of left ventricular aneurysm. Functional, clinical,
      and electrophysiological results.
AB  - BACKGROUND: Recent advances in surgical techniques for the repair of left
      ventricular aneurysms (LVAs) include the use of an endoventricular patch to
      exclude the aneurysm cavity. This technique has replaced conventional linear
      plication of the aneurysm. The endoventricular patch technique remodels the left
      ventricular cavity to a more physiological geometry that improves function.
      METHODS AND RESULTS: From December 1989 through November 1993, 45 patients
      underwent an LVA repair with an endoventricular patch. This procedure was
      performed in association with coronary artery bypass grafting in 40 patients.
      Twenty-eight patients (62.2%) also had nonguided encircling subendocardial
      incisions. Operative procedures included 7 emergency operations, 3 concomitant
      valve procedures, and a mean of 2.2 bypass grafts per patient. Eight patients had
      previous cardiac operations. Hospital mortality was 15.6% (7/45) for all patients
      and 9.1% (3/33) for nonemergent revascularization and LVA repairs. Ejection
      fraction improved from a mean of 25.8% preoperatively to 37.8% postoperatively;
      the mean New York Heart Association classification improved from 3.5 to 1.5. Of
      patients known to have preoperative arrhythmias (inducible or sudden death), 69%
      were not inducible postoperatively without antiarrhythmic medication. Survival
      from late cardiac death (including death of unknown origin) was 86.5% at 2 years.
      Freedom from documented ventricular arrhythmias was 94.3% at 2 years.
      CONCLUSIONS: These results indicate that the patch endoaneurysmorrhaphy technique
      can provide an excellent functional and physiological outcome in patients with
      LVAs and severely impaired ventricular function.

PMID- 7586469
TI  - Which is the graft of choice for the right coronary and posterior descending
      arteries? Comparison of the right internal mammary artery and the right
      gastroepiploic artery.
AB  - BACKGROUND: The graft of choice for the left anterior descending coronary artery
      is the left internal mammary artery because of superior long-term patency.
      However, controversy exists regarding the graft of choice for the right coronary
      artery and for the posterior descending branch. METHODS AND RESULTS: Two types of
      pedicled arterial grafts were used for the right coronary and the posterior
      descending arteries in patients undergoing coronary bypass surgery between
      January 1991 and September 1994. Group A comprised 114 patients with a right
      internal mammary artery (RIMA) graft, and group B consisted of 127 patients with
      an in situ right gastroepiploic artery (R-GEA) graft. Mean age was 56.9 years in
      group A and 63.3 years in group B; 7.9% (9 of 114) and 33.9% (43 of 127) were
      diabetics in groups A and B, respectively. Overall mortality was 2.6% (3 deaths)
      for group A and 3.9% (5 deaths) for group B (P = NS). However, the prevalence of
      perioperative myocardial infarction in the right coronary artery distribution was
      significantly higher for group A (5.3%, or 6 of 114) than for group B (0.8%, or 1
      of 127; P < .05), and the reoperation rate for graft failure (from 0 to 12 months
      after surgery) was significantly higher for the RIMA (4.4%, or 5 of 114) than for
      the R-GEA (0%; P < .05). Also, the prevalence of deep sternal wound infection in
      diabetics was significantly higher in group A (22.2%, or 2 of 9) than in group B
      (4.6%, or 2 of 43; P < .05). CONCLUSIONS: Our preliminary results suggest that
      the failure rate of the RIMA graft is significantly higher, especially if used as
      a pedicled graft to the posterior descending artery. The risk of sternal wound
      complications is greater in diabetics if both internal mammary arteries are used
      for grafting. Therefore, the R-GEA graft is preferred in diabetics and whenever
      the posterior descending artery is the target vessel.

PMID- 7586471
TI  - Swimming with the current.

PMID- 7586472
TI  - Quantitative cleaning efficacy evaluation methods with protein and lipid lens
      soiling models.
AB  - We developed a nondestructive, quantitative method for evaluating the cleaning
      efficacy of rigid gas permeable contact lens care systems. Simulated tears
      prepared with lysozyme, albumin, and calcium ions were applied to rigid gas
      permeable lenses as a protein soiling model, and a mixture of grease and
      unsaturated fat was applied as a lipid soiling model. The ComfortCare system
      (Pilkington Barnes Hind) and the Boston Cleaner and Boston Conditioning Solution
      (Polymer Technology) were evaluated for their efficacy in removing protein
      deposits; water was used as a control. The ComfortCare system and the Boston
      Advance Cleaner and Boston Advance Conditioning Solution were evaluated for their
      effectiveness in removing lipid deposits; saline was used as a control. Protein
      deposit level was detected by a densitometer at the absorbance of 280 nm. The
      lipid deposit level was evaluated by the absorbance of the fluorescence at 430 nm
      using the same densitometer with a fluorescence accessory. The two test systems
      demonstrated a significantly higher cleaning efficacy than the control for both
      soiling models. The methods provide quantitative measurements and therefore can
      be analyzed statistically for screening or comparison purposes.

PMID- 7586473
TI  - Tear LTC4 levels in patients with subclinical contact lens related giant
      papillary conjunctivitis.
AB  - We determined the tear levels of LTC4 in contact lens wearers who had minimal
      irritative symptoms and signs suggesting subclinical conjunctival abnormalities
      and the possible development of giant papillary conjunctivitis (GPC). We examined
      25 patients wearing rigid gas permeable lenses. Ten of the contact lens wearers
      had minimal irritative symptoms and nonspecific papillary hypertrophy, and 15
      patients had no symptoms. We included eight controls chosen from the same age
      group who were not contact lens wearers and who had normal conjunctiva. Tear
      samples were examined through the ELISA technique. Elevated levels of LTC4 were
      found in the tears of symptomatic patients (525.50 +/- 202 pg/mL) compared with
      tears of asymptomatic contact lens wearers (52.6 +/- 10.2 pg/mL) and the control
      group (75 +/- 8.4 pg/mL) (P < 0.001). Two patients in the first group developed
      GPC in the course of their follow-up. The results of this study indicate that
      detecting tear LTC4 levels in contact lens wearers can give useful information
      regarding the presence of contact lens related subclinical inflammation and
      subclinical GPC.

PMID- 7586474
TI  - Soft toric lens power accuracy and reproducibility.
AB  - Lens power accuracy is the most frequently cited requirement for reproducible
      soft toric lens performance. Power accuracy is even more critical with planned
      replacement soft toric lenses because of the increased rate at which lenses are
      replaced. However, no reproducible methodology exists for making such an
      evaluation. We developed a power measurement method from which measurement error
      was eliminated. Geometric optical calculation was used to calculate the resulting
      optical error. The relationship between visual acuity loss and optical errors was
      used to predict the effect on visual acuity. This method was applied to a sample
      of 457 Focus Toric soft contact lenses. We found that 83.5 +/- 1.7% of the lenses
      were accurate enough to deliver one line or less of loss in visual acuity. Our
      estimate of the clinical problem rate associated with power reproducibility was
      3.3 +/- 0.9% of lens pairs. If lenses were replaced on a monthly basis, this
      would amount to one problem pair every 30 months.

PMID- 7586475
TI  - In vitro ocular irritancy measure of four contact lens solutions: damage and
      recovery.
AB  - We measured the potential toxicity of four contact lens solutions using an in
      vitro approach in which the optical quality of the cultured bovine lens was
      measured as a function of exposure to each substance tested. This approach uses
      an automated scanning laser to measure the focal variability of lenses contained
      in special culture cells and maintained under long-term culture conditions. The
      products tested included three rigid gas permeable contact lens conditioning
      solutions (Boston Conditioning Solution, Boston Advance Conditioning Solution,
      and a new formulation of Boston Advance Conditioning Solution [Polymer
      Technology]) and one soft contact lens disinfecting system (OptimEyes; Core
      Technologies). The results indicate a wide range of toxicologic potential that
      corresponds, on a relative basis, with published in vivo evaluation of the same
      substances. Moreover, the results demonstrate that this in vitro system can be
      used to evaluate the potential for recovery from damage caused by the four
      solutions tested.

PMID- 7586477
TI  - Corneal topography in contact lens wearers following penetrating keratoplasty.
AB  - We examined the effects of contact lens wear on corneal topography following
      penetrating keratoplasty (PK). We present the long-term follow-up of 23 eyes of
      22 patients who underwent PK and rigid gas permeable contact lens fitting.
      Computerized corneal topography, manual keratometry, and refraction were
      conducted prior to contact lens fitting and then at 2 weeks, 6 weeks, 3 months, 6
      months, and 1 year post-fitting. At least 6 months follow up was obtained for 23
      eyes of 22 patients, and at least 12 months follow-up was obtained for 18 eyes of
      17 patients. Seventy four percent of the eyes were stable (+/- 1.00 D) by manual
      keratometry, computerized corneal topography, and refraction (both spherical
      equivalent and cylinder). Those patients who changed showed a trend toward a
      small decrease in refractive cylinder and spherical equivalent. Measurements
      obtained from both computerized corneal topography and manual keratometry showed
      a small but significant amount of flattening (P < 0.003 and P < 0.04,
      respectively).

PMID- 7586478
TI  - Relationship between corneal edema and topography.
AB  - We found that corneal edema can occur without significant concomitant changes in
      central and peripheral corneal topography. We examined the relationship between
      corneal edema and corneal topography in 10 subjects with normal ocular
      examinations. Baseline pachymetry and topographic measurements for both eyes of
      each patient were obtained. The right eye of each subject was exposed to an
      anoxic environment for 2 hours using a nitrogen chamber goggle. The left eye
      served as control. Optical pachymetry and computerized corneal topographic
      measurements were taken for both eyes immediately after removal of the nitrogen
      chamber goggle. All corneas exposed to the nitrogen chamber were thickened in all
      areas after removal of goggles. Average percent thickening per area was: 16.4%
      centrally, 6.3% nasally, 6.0% temporally, 6.3% superiorly, and 9.2% inferiorly.
      Corneas exposed to the nitrogen chamber demonstrated no significant topographic
      changes, except in the nasal area where the corneal power lessened. Furthermore,
      there was no significant correlation between corneal thickening in any area
      measured and changes in corneal topography. Control corneas did not thicken or
      demonstrate significant topographic changes.

PMID- 7586476
TI  - Role of the post-lens tear film in the mechanism of inferior arcuate staining
      with ultrathin hydrogel lenses.
AB  - We studied the depletion of the post-lens tear film as contributing to inferior
      arcuate staining with ultrathin high water content hydrogel lenses. We monitored
      the post-lens tear film specular reflection of hydrogel lenses (0.04 mm center
      thickness, 67% nominal water content), which caused inferior arcuate staining. A
      standard thickness (0.12 mm) lens was worn in the contralateral eye as a control
      condition. Lenses were worn for a 2 hour period by 20 subjects. Post-lens tear
      film appearances were categorized as amorphous, faint colored, or colored, where
      the colored patterns represented a relatively depleted post-lens tear film. We
      also measured lens dehydration, lens adherence, and pre-lens tear film stability
      in order to evaluate their role in inferior arcuate staining. The ultrathin and
      standard lenses caused staining in 100 and 75% of subjects, respectively; the
      severity of staining was much greater with the ultrathin lenses (Wilcoxon signed
      ranks test, P = 0.0004). The ultrathin lenses were associated with a higher
      incidence of post-lens tear film depletion (P = 0.018), had greater front surface
      dehydration (P = 0.0004), and were more adherent to the eye (paired t-test, P =
      0.001). However, pre-lens tear thinning times were not significantly different
      between the two lens types (Wilcoxon signed ranks test, P > 0.05). These findings
      support the contention that post-lens tear film depletion is a component of a
      lens adherence or lens dehydration mediated mechanism of inferior arcuate
      staining.

PMID- 7586479
TI  - Examination of the conjunctival microbiota after 8 hours of eye closure.
AB  - We investigated the effect of overnight eye closure on the levels and types of
      microbiota in the external eye, the conjunctiva, and lid margins of 40 normal
      subjects during the day and immediately after eye opening following 8 hours of
      sleep over 3 consecutive days. Overall, clinically important levels of gram
      positive bacteria were isolated from 22.1% of samples; 2.3% of samples yielded
      gram-negative bacterial growth. The incidence of clinically important levels of
      gram-positive bacteria was greater in closed-eye compared with open-eye samples.
      There was no significant increase in the incidence of gram-negative bacteria or
      fungi with eye closure. There was no difference between the open- and closed- eye
      samples with regard to types of microorganisms isolated. Our results suggest that
      eye closure may promote the growth of normal external ocular microbiota. These
      findings have implications for extended contact lens wear and ocular surgery.

PMID- 7586480
TI  - Chronic blepharitis: a review.
AB  - Although blepharitis is one of the most common ocular disorders encountered in
      clinical practice, it may constitute a diagnostic and therapeutic enigma.
      Attempts to classify this disorder are difficult because of the complex
      mechanisms underlying its pathogenesis. Clinical and laboratory investigations
      have clearly established bacteria and meibomian gland abnormalities as major
      etiologic determinants. In addition, changes in tear film dynamics and underlying
      dermatologic abnormalities appear to contribute to pathogenesis. The clinical
      manifestations primarily occur along the lid margin, and the predominant symptoms
      are itching and burning. Currently there is no cure for this condition. In the
      case of staphylococcal blepharitis, for example, there is no long-term cure
      because patients are likely susceptible to the causative organism(s), and thus
      become reinfected. Therapy is aimed then at bringing the disease process under
      control. A therapeutic regimen consisting of lid hygiene, topical or systemic
      antibiotics, and tear replacement seems to be most effective in alleviating
      symptoms and maintaining disease control but requires prolonged treatment.

PMID- 7586482
TI  - The endoscope and infection transmission: the problems and how to avoid them.

PMID- 7586481
TI  - Role of metformin in type II diabetes.

PMID- 7586483
TI  - A 47-year-old woman with a swollen leg.
AB  - This case illustrates the importance of expanding the differential diagnosis
      beyond ruling out a DVT in a patient presenting with calf swelling. A good
      history and examination and a compulsive search for an etiology are necessary in
      the pursuit of the correct diagnosis. In this patient, only after identifying the
      popliteal cyst and recognizing that it represented an inflammatory synovitis
      could the cause be determined and the proper treatment instituted.

PMID- 7586484
TI  - Coronary heart disease in African Americans: primary and secondary prevention.
AB  - Coronary heart disease develops sooner in African Americans than in whites and
      causes a higher rate of mortality. Because multiple risk factors and risk factor
      clustering are common, efforts at primary and secondary prevention in this
      population need to address the total risk-factor profile.

PMID- 7586485
TI  - Asthma: current controversies and emerging therapies.
AB  - Despite advances in understanding the pathogenesis of asthma, a number of
      controversies regarding the optimal clinical management of asthma remain. This
      review of recent literature and current controversies, chosen mainly on the basis
      of relevance to clinical therapy, is directed toward nonspecialists caring for
      asthmatic patients.

PMID- 7586486
TI  - Evaluating unexplained syncope with upright tilt testing.
AB  - Trials of upright tilt testing for vasovagal syncope are difficult to evaluate,
      owing to differing methods used and the lack of a gold standard with which to
      compare this test. This paper reviews the studies to date and offers
      recommendations for the clinical use of this test.

PMID- 7586487
TI  - Accuracy and predictive values in clinical decision-making.
AB  - In clinical practice, the accuracy and predictive values of a diagnostic test may
      differ substantially from values cited in published reports, owing to a lower
      prevalence of most diseases in clinical populations than in study populations. To
      correct this problem, published assessments of diagnostic tests should
      standardize accuracy and predictive values to account for disease prevalence.

PMID- 7586488
TI  - Use of old and new oral 5-aminosalicylic acid formulations in inflammatory bowel
      disease.
AB  - Although sulfasalazine, a 5-aminosalicylic acid (5-ASA) agent, is still the anti
      inflammatory agent of choice for ulcerative colitis and Crohn's disease, newer
      formulations, which release drug to specific regions of the colon for maximal
      efficacy, also can be appropriate first-line agents. This article reviews recent
      clinical studies of therapy with older and newer 5-ASA formulations.

PMID- 7586489
TI  - An update on prostate cancer.
AB  - As screening for prostate cancer has become more common, the issues surrounding
      its diagnosis and treatment have grown more complex. This review surveys recent
      advances and controversies, including definition of risk factors, the role of
      screening, and current treatment strategies.

PMID- 7586491
TI  - Ontogenetic development of histamine receptor subtypes in rat brain demonstrated
      by quantitative autoradiography.
AB  - The postnatal ontogenetic development of the histamine receptor subtypes was
      studied in rat brain by quantitative receptor autoradiography with highly
      sensitive imaging plates. H1 receptor binding sites labeled with [3H]pyrilamine
      were detected on postnatal day 2 (P2) and increased very slowly until P9, and
      then rapidly reaching the adult levels in the hypothalamus, hippocampus, and
      amygdala by P16. The densities of H1 receptor binding sites in the cortex,
      striatum, thalamus, and substantia nigra were relatively low during development.
      H3 receptor binding sites labeled with [3H](R) alpha-methylhistamine were not
      detectable until P9. On P9, their density was higher in the substantia nigra than
      in other regions. Subsequently, H3 receptor binding increased, reaching the adult
      levels in the substantia nigra on P16 and in the other regions on P23. The
      histamine concentration was initially very high, but decreased to the adult level
      by P16. On the contrary, the activity of L-histidine decarboxylase of whole brain
      tissue was low on P5, and increased markedly from P16 to P23, to the adult level
      on P30. Administration of (S) alpha-fluoromethylhistidine (FMH), a specific
      inhibitor of L-histidine decarboxylase (HDC), significantly decreased both the
      HDC activity and histamine concentration during postnatal development. FMH
      treatment did not change H1 receptor binding in any brain region, but
      significantly increased H3 receptors in the substantia nigra and striatum on P23.
      Unilateral injection of 6-hydroxydopamine into the striatum on P2 resulted in up
      regulation of H3 receptor binding sites in the dorsomedial (11%) and dorsolateral
      (18%) regions of the striatum and substantia nigra (31%) on P23, but no change in
      the H3 receptor density in the nucleus accumbens or frontal cortex on P11 and
      P23. These results demonstrate that the developmental patterns of H1 and H3
      receptors are heterogeneous and independent of each other. There are marked
      mismatches of presynaptic and postsynaptic markers of the histaminergic neuron
      system as in other aminergic systems.

PMID- 7586492
TI  - Induction of NCAM expression in mouse olfactory keratin-positive basal cells in
      vitro.
AB  - The expression of neural cell adhesion molecule (NCAM) by olfactory keratin+
      basal cells was investigated in vitro. In primary cultures from embryonic day
      14.5 or newborn mouse olfactory epithelium (OE), flat keratin+ basal cells were
      negative for NCAM-immunostaining. Transforming-growth factor-beta 1, beta 2 (TGF
      beta 1, beta 2) or a high concentration of Ca2+ induced these cells to express
      NCAM. We obtained a cell line, designated DBC1.2, from embryonic day 14.5 mouse
      OE. All DBC1.2 cells were positive for keratin-immunostaining, whereas nearly all
      cells were negative for NCAM-immunostaining. Therefore, DBC1.2 cells seemed to
      derive from dark basal cells. DBC1.2 cells were also induced to express NCAM by
      the treatment with TGF-beta s or a high Ca2+ concentration. Western blotting
      revealed that the components of the NCAM expressed by DBC1.2 were 120 and 140
      kDa, but not 180 kDa, isoforms. Since NCAM is the cell adhesion molecule mainly
      expressed in nervous tissues, these results suggest a cell lineage relationship
      or interactions between olfactory keratin+ basal cells and olfactory sensory
      neurons.

PMID- 7586493
TI  - Cocaine stimulation of ovine fetal swallowing.
AB  - Cocaine acts to block reuptake of neurotransmitters, resulting in elevated intra
      synaptic norepinephrine levels. As monoaminergic systems may contribute to
      central regulation of swallowing motor activity as well as dipsogenic responses,
      and cocaine is known to alter fetal behavior, we examined the effect of
      intravenous cocaine on fetal swallowing. Six ovine fetuses (130 +/- 1 days) were
      chronically prepared with esophageal electrodes and an esophageal flow probe.
      Following a 1-h control period, fetuses received an intravenous injection of 1.0
      mg/kg cocaine over 30 s. Fetal blood samples were withdrawn at timed intervals
      and fetal swallowing activity was monitored for 180 min after the cocaine bolus.
      Basal fetal swallowing activity during the control period was 0.6 +/- 0.1
      swallows/min, with esophageal flow of 0.3 +/- 0.1 ml/min. At 10 min following
      cocaine, fetal swallowing rate increased to 1.4 +/- 0.4 swallows/min though
      esophageal flow did not change significantly (0.4 +/- 0.2 ml/min). Swallowing
      rate then returned to basal levels. Fetal heart rate increased in response to
      cocaine injection (149 +/- 14 to 174 +/- 24 bts/min at 180 min) though there was
      no change in fetal mean blood pressure. These results demonstrate acute
      stimulation of fetal swallowing activity in response to intravenous cocaine
      injection. Together with previous reports, these data further illustrate the
      diversity of fetal behavioral effects in response to in utero cocaine exposure.

PMID- 7586490
TI  - Using the tilt test to diagnose cause of syncope.

PMID- 7586494
TI  - Corticotropin-releasing factor modulation of the ultrasonic vocalization rate of
      isolated rat pups.
AB  - The effect of corticotropin-releasing factor (CRF) on ultrasonic vocalizations
      (USVs) and other behaviors of isolated rat pups was examined at 5/6-, 9/10-, and
      13/14-days. The hypothesis tested was that central CRF affects USV rate
      biphasically: as endogenous CRF increases from low basal levels it initiates USV
      production, but at higher levels CRF diminishes USV production. As predicted, the
      largest doses of CRF (0.1 and 1 microgram) and of its antagonist alpha-helical
      CRF9-41 (aH-CRF; 20 micrograms) administered intracerebroventricularly (ICV)
      reduced USV rate compared to saline treatment during a 2-min isolation at ambient
      temperature in pups of all ages. Other behaviors were either unaffected or
      increased by drug treatment. Effects were not attributable to sedation or to a
      change in core temperature. Peripheral administration of 1 microgram CRF or 20
      micrograms aH-CRF had no effect. When isolation occurred in a heated chamber
      containing soiled bedding from the home cage to minimize baseline USV rate, ICV
      CRF (0.001, 0.01, 0.1, or 1 microgram) did not enhance the rate. The quieting
      ability of aH-CRF is evidence that central endogenous CRF enhances the rate of
      ongoing USVs during brief isolation; the quieting ability of CRF suggests that
      this peptide may also be responsible for the reduction in USV rate that normally
      occurs during more protracted isolation. However, CRF alone is not sufficient to
      induce vocalizing in quiet pups.

PMID- 7586495
TI  - NMDA antagonism during development extends sparing of hindlimb function to older
      spinally transected rats.
AB  - Hindlimb weight support and bipedal stepping occur after spinal cord transection
      in neonatal rats (birth to 12 days of age) while the same lesion in 15-day and
      older animals results in permanent loss of these responses. Some compensatory
      change in lumbar spinal circuitry must occur after spinal transection in young
      animals subserving these hindlimb behaviors. In contrast, animals just a few days
      older are incapable of such compensatory responses. We have examined the
      hypothesis that neural activity leads to the postnatal loss of plasticity in
      spinal circuitry. We find that antagonism of the N-methyl-D-aspartate (NMDA)
      subtype of glutamate receptor with MK-801 in young animals extends the sparing of
      hindlimb function after spinal transection to older animals. This effect is not
      due to a non-specific depression of all exciatory drive to motor neurons since Ia
      to motor neurons synaptic transmission through non-NMDA receptors is preserved
      during MK-801 treatment. Acute administration of MK-801 at the time of spinal
      transection or chronic administration of MK-801 after postnatal day 17 has no
      effect on recovery of hindlimb function after spinal transection. These results
      highlight the importance of NMDA receptor activation in spinal circuit
      maturation.

PMID- 7586496
TI  - Properties of low Mg2+ induced epileptiform activity in rat hippocampal and
      entorhinal cortex slices during adolescence.
AB  - Properties of low Mg2+ induced epileptiform activity were studied in isolated rat
      hippocampal slices or in combined slices containing the entorhinal cortex and
      hippocampus. Slices were prepared from rats which were 1, 2, 3 or more weeks of
      age. Field potentials and often also changes in [K+]0, [Ca2+]0 and [Mg2+]0 were
      recorded with appropriate ion selective microelectrodes. In isolated hippocampal
      and entorhinal cortex/hippocampal combined slices the latency to onset of
      epileptiform activity upon lowering of extracellular Mg2+ was shortest in the
      youngest age group and approached adult levels at about the fourth postnatal
      week. Washout kinetics of Mg2+ were fastest in slices from 1-week-old rats. The
      onset of low Mg2+ induced epileptiform activity occurred at higher Mg2+ levels in
      slices from young compared with those from adult animals. In isolated hippocampal
      slices the epileptiform discharges varied in appearance during development. Short
      discharges lasting for 40 to 80 ms were observed in hippocampal slices prepared
      from 1-week-old and adult animals. Seizure-like events (SLE's) characterized by
      slow negative potential shifts and characteristic elevations in [K +]0 and
      decreases in [Ca2+]0 lasting for up to 30 s were observed in a proportion of
      hippocampal slices prepared after the first, second and third postnatal week. In
      slices from week 2 and 3 seizure-like events often progressed into spreading
      depressions (SD's). In entorhinal cortex/hippocampal combined slices seizure-like
      events were observed in all age groups. The seizure-like events spread readily
      into dentate gyrus (DG), area CA3 and CA1 after week 1.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7586497
TI  - Functional expression of voltage dependent sodium channels in Xenopus oocytes
      injected with mRNA from neonatal or adult rat brain.
AB  - The two electrode voltage clamp technique was used to study voltage-dependent
      sodium currents (INa) in Xenopus laevis oocytes previously injected with mRNA
      extracted from adult (A) or neonatal (N, < 5 days old) rat brains. In the
      presence of niflumic acid (300 microM) to block endogenous Ca(2+)-activated Cl-
      currents, depolarizing voltage steps from a holding potential of -100 mV to
      various voltages elicited in both groups of oocytes fast inward sodium currents
      which peaked at approximately 0 mV and then slowly declined to approximately 75%
      of the maximum current at +40 mV. At the peak, A INa was significantly larger
      than N INa (296 +/- 59 nA vs. 147 +/- 32 nA). Inactivation kinetics of N INa was
      best fit with one exponential component whereas A INa with two exponential
      components. A significant difference in the voltage dependence of inactivation
      was found between A INa or N INa. The values of Vh were -53 +/- 0.9 mV or -59.8
      +/- 0.7 mV for A INa or N INa respectively. The recovery from inactivation was
      fitted in both groups with two exponential functions (tau f and tau s) whose
      values were not significantly different. However the ratio between tau f and tau
      s was significantly higher for N INa comparing to A INa (5.7 vs. 2.1). TTX
      reversibly blocked INa. The IC50 value was 58.2 +/- 6.3 nM for A INa and 20.4 +/-
      2.2 nM for N INa. These results suggest that different isoforms of TTX-sensitive,
      voltage-dependent sodium channel subunits are functionally expressed, may be in
      different proportions in oocytes injected with A or N mRNA.

PMID- 7586498
TI  - Peptidergic, catecholaminergic and morphological properties of avian chromaffin
      cells are modulated distinctively by growth factors.
AB  - Most neurons and endocrine cells are known to co-express a 'classical
      neurotransmitter' with one or more neuropeptides. Although their expression has
      been shown to be modulated by differentiation factors, it is not known if
      particular combinations of neurotransmitter/neuropeptide(s) are co-regulated. We
      have analyzed the effect of nerve growth factor (NGF), neurotrophin-3 (NT-3),
      brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF),
      basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF
      beta 1) on the modulation of neuroactive substances co-expressed by avian
      chromaffin cells. The content of the neuropeptides neuropeptide Y (NPY),
      enkephalin (ENK) and somatostatin (SS) was measured by radioimmunoanalysis, and
      the content of the catecholamines norepinephrine (NE) and epinephrine (E) by high
      pressure liquid chromatography-electrochemistry (HPLC-EC). In addition, the
      morphological differentiation of chromaffin cells in response to the growth
      factors was assessed. All of the studied factors had distinct effects on the
      chromaffin content of neuropeptides and catecholamines. Our results show that the
      modulation of CAs and neuropeptides, and among the neuropeptides themselves is
      completely dissociated. Moreover, the cellular responses to the different growth
      factors show that neurochemical properties are modulated independently of
      morphological ones.

PMID- 7586500
TI  - Motoneuron reinnervation of phasic uropod muscles in crayfish.
AB  - Motoneuron reinnervation of the lateral abductor and adductor muscles in the
      exopodite of the crayfish uropod was obtained by cross-tying the cut proximal
      ends of one set of uropod nerve roots to the cut distal ends of their
      contralateral homologues. In normal (nonsurgically treated) animals the abductor
      was innervated by two excitatory motoneurons and an inhibitor while two excitors
      innervated the adductor. For each muscle one of the excitors produced large
      excitatory junction potentials (EJPs) while the other evoked small EJPs. When
      stimulated repetitively only the smaller EJP in the adductor generated a
      facilitating response. Within less than 10 weeks postsurgery the muscles were
      each reinnervated by two excitatory motoneurons. While the abductor motoneurons
      generated synaptic potentials with similar amplitudes and time courses to those
      of normal animals, they differed from those in normal animals in that they
      facilitated when stimulated repetitively. In contrast to the large and small EJPs
      evoked in the normal animal, the two motoneurons that reinnervated the adductor
      muscle elicited similar amplitude EJPs, neither of which facilitated in response
      to repetitive stimulation.

PMID- 7586499
TI  - Abnormal ipsilateral functional vibrissae projection onto Purkinje cells multiply
      innervated by climbing fibers in the rat.
AB  - We have previously shown that synapse elimination occurring in the climbing fiber
      (CF)-Purkinje cell (PC) relationships during normal postnatal development is
      likely involved in the refinement of vibrissae projections onto the cerebellar
      cortex. In normal adult rats, CF-mediated vibrissae projections onto cerebellar
      Purkinje cells of the vermis of lobule VII are strictly contralateral and located
      in a narrow microzone whereas they are widely distributed in rats whose PCs
      remained multiply innervated by CFs due to postnatal irradiation. Given the
      proximity of this microzone to the midline, the question arose as to whether this
      synapse elimination process could participate in the segregation of ipsilateral
      and contralateral projections. In the present study, we compared the
      topographical map of the ipsilateral and contralateral CF-mediated projections of
      the third row of vibrissae onto the vermal PCs of lobule VII in adult normal rats
      and in polyinnervated rats. Using intracellular electrophysiological recordings,
      we examined the responsiveness of PCs to mechanical stimulation of vibrissae, and
      positioned responsive cells on an averaged planar map of lobule VII. In normal
      rats no ipsilateral responses were found, while in irradiated rats ipsilateral
      responses were distributed evenly from the midline to 700 microns apart. These
      results suggest that synapse elimination participates in the segregation of ipsi
      and contralateral mystacial inputs to the vermis.

PMID- 7586501
TI  - Age-related mu-, delta-and kappa-opioid ligands in respiratory-related brain
      regions of piglets: effect of prenatal cocaine.
AB  - Neonates, as compared to older subjects, exhibit increased signs of relative
      respiratory suppression such as apnea, periodic breathing and only transient
      hyperventilatory response to hypoxia. Prenatal cocaine exposure exaggerates the
      respiratory pattern disturbances observed in infants. As endogenous opioids cause
      central suppression of breathing, we tested their possible involvement in these
      effects by assessing opioid content in respiratory-related brainstem regions of 2
      to 5 (young) and 18 to 22 (older) day-old piglets, unexposed or preexposed to
      cocaine during 0.66 to 1.0 gestation. The selected ages represent distinct stages
      in the postnatal development of respiration. beta-Endorphin, methionine
      enkephalin, dynorphin A and dynorphin B from the tractus solitarii, ambigualis,
      gigantoreticularis and parabrachialis medialis nuclei were separated by high
      performance liquid chromatography, then quantified by radioimmunoassays. Opioid
      content was higher in the brain regions of the young than of the older piglets,
      and increased after cocaine exposure in both age groups, but more in the young.
      These findings support the possible contribution of high opioid content to the
      relative suppression of respiratory function in early life, and to the
      exaggerated respiratory dysrhythmia observed in cocaine preexposed neonates.

PMID- 7586502
TI  - Regional cerebral metabolic consequences of bilirubin in rat depend upon post
      gestational age at the time of hyperbilirubinemia.
AB  - While the accumulation of bilirubin in specific brain regions has been well
      characterized at autopsy in kernicteric infants, data on the regional effects of
      early cerebral bilirubin intoxication are still missing. Therefore, the
      quantitative autoradiographic [14C]2-deoxyglucose technique was applied to the
      measurement of the effects of a bilirubin infusion on local cerebral metabolic
      rates for glucose (LCMRglc) in immature rats. A loading dose of 80 mg/kg
      bilirubin was first administered to the animals over 15 min. Thereafter, the
      velocity of the infusion was reduced to 32 mg/kg/h and the infusion was continued
      for 105 min. The animals were studied at two ages, postnatal day 10 (P10) and
      P21. The [14C]2-deoxyglucose was injected to the animals 45 min before the end of
      the infusion. Bilirubin infusion led to plasma concentrations ranging from 100 to
      200 mumol/l at both ages and to brain amounts of 10-16 nmol/g at P10 while
      bilirubin was not detectable in brain at P21. Hyperbilirubinemia induced
      widespread decreases in LCMRglcs at P10 and had rather limited consequences on
      cerebral glucose utilization at P21. At P10, decreases in LCMRglcs were mostly
      prominent in regions that have been shown to preferentially accumulate bilirubin
      in kernicteric infants. In conclusion, there appears to be a good correlation
      between these metabolic data and regional brain permeability to bilirubin.

PMID- 7586503
TI  - Developmental profile of non-heme iron distribution in the rat brain during
      ontogenesis.
AB  - The entry of iron from blood into the developing rat brain was studied by means
      of non-heme iron-histochemistry. The content of non-heme iron in the endothelial
      cells was manifest already from E14, declined from P3 to P5, and was almost
      absent on P10-P15. The choroid plexus epithelial cells of either ventricle was
      non-heme iron-containing from E14. Non-heme iron-containing macrophages situated
      in the stroma of the choroid plexus were also observed from E14. From E19, the
      macrophage-like cells tended to invade into (a) regions with transitory
      structures like the intermediate zone of the cerebral hemisphere, (b) developing
      axonal tracts like corpus callosum and internal capsule, and (c) deep layers of
      the tectum, a region with an extensive degree of naturally occurring cell death.
      The amoeboid macrophage-like cells observed in the brain parenchyma gradually
      acquired prolonged extensions and apparently differentiated into ramified
      microglia-like cells, which later lost their non-heme iron-content. Thus, at P70,
      non-heme iron-positive microglia-like cells were hardly seen reflecting the
      transitory event of non-heme iron in microglia-like cells. At P200, non-heme iron
      containing microglia cells and oligodendrocytes appeared in manifestly higher
      number than at P70, a phenomenon probably related to aging. These results
      delineate for the first time the appearance of iron in the developing brain. The
      results are of relevance for understanding the potential of iron-deficiency for
      harming the developing central nervous system, generally by decreased transport
      of iron through brain capillaries and choroid plexus, and specifically by an
      impaired modulation of the developing brain parenchyma by iron-containing
      macrophages.

PMID- 7586504
TI  - Transient functional connections between the developing corticospinal tract and
      cervical spinal interneurons as demonstrated by c-fos immunohistochemistry.
AB  - Previous research on the rat corticospinal tract (CST) which develops mainly
      postnatally revealed that some CST axons grow transiently into the spinal gray
      matter and are subsequently eliminated. In the present study the question was
      addressed whether these fibres also form transient functional connections. Rats
      aged 14 and 60 days postnatally received unilateral injections of the potent
      glutamate agonist kainate into the cerebral motor cortex. After a survival period
      of 90 min. the rats were perfused and their brains and spinal cords processed for
      the immediate early gene c-fos by immunohistochemistry. Increased levels of c-fos
      as opposed to sham-operated animals was observed in several brain nuclei as well
      as in the cervical spinal cord. In the spinal gray one population of labelled
      interneurons in particular appeared to correlate well with the CST projection
      field. A decrease was noted in the number of c-fos positive neurons from
      postnatal day 14 to 60, suggesting that during development transient functional
      connections are formed between the CST and its target.

PMID- 7586505
TI  - Effects of leukemia inhibitory factor on the differentiation of astrocyte
      progenitor cells from embryonic mouse cerebral hemispheres.
AB  - The effects of leukemia inhibitory factor (LIF) on the differentiation and
      proliferation of astrocyte progenitor cells in an enriched culture were studied.
      The astrocyte progenitor cells obtained from embryonic mouse cerebral hemispheres
      were enriched by subculturing twice in serum-free medium containing epidermal
      growth factor (EGF). They exhibited a flat, non-process-bearing morphology and
      were negative for glial fibrillary acidic protein (GFAP), a specific marker for
      astrocytes. Culture of the cells with LIF resulted in the expression of GFAP and
      in the inhibition of growth. These results suggest that LIF promotes the
      differentiation of astrocyte progenitor cells.

PMID- 7586508
TI  - Direct DNA sequencing in the clinical laboratory.

PMID- 7586507
TI  - Developmental changes of apolipoprotein E immunoreactivity in Down syndrome
      brains.
AB  - The temporal profile of apolipoprotein-E (apo-E) expression was investigated
      immunohistochemically in the brains of Down syndrome patients and of normal
      controls. The number of apo-E immunoreactive astrocytes in the frontal cortex was
      larger in Down syndrome patients than in controls from 7 months to 24 years of
      age. It suggests that apo-E producing astrocytes in the early phase of
      pathological process lead to presenile dementia in Down syndrome patients. In
      contrast, the number in the white matter was smaller in Down syndrome patients
      from 28 gestational weeks to 5 years. Apo-E immunoreactive senile plaques were
      noted in Down syndrome brains from the age of 25 years, while APP
      immunoreactivity was first noted in senile plaques at the age of 32 years.

PMID- 7586509
TI  - Can molecular markers now be used for early diagnosis of malignancy?
AB  - Most of the presently available cancer markers are neither specific for
      malignancy nor allow early diagnosis. However, the recent elucidation of the
      molecular events occurring during tumorigenesis may provide new markers that are
      likely to be both specific for cancer and sensitive for early disease. The key
      molecules undergoing alterations during carcinogenesis are the cellular oncogenes
      and suppressor genes. Alterations in these genes can be detected in cells shed
      from malignant and premalignant lesions. Thus, mutant p53 genes have been found
      in urine from patients with bladder cancer, mutant ras genes in stools from
      patients with colorectal and pancreatic cancers, and both mutant p53 and ras
      genes in sputum from patients with lung cancer. These findings show that the
      genetic alterations in cancer can be detected in fluids or secretions that had
      contact with the malignant tissue. The preliminary studies, however, had small
      numbers of both patients and controls and used time-consuming, labor-intensive,
      and expensive assays. For routine applications, these assays must be simplified,
      automated, and tested for sensitivity, specificity, and predictive value.

PMID- 7586506
TI  - Calmodulin, calbindin-D28k, calretinin and neurocalcin in rat olfactory bulb
      during postnatal development.
AB  - Odorant stimulation of receptor cells results in a calcium influx that activates
      the transduction pathway. The olfactory neurons extend axons to the olfactory
      bulb where they synapse onto mitral cells. Ca(2+)-acceptors also may participate
      in subsequent processing of olfactory information. The present study describes
      the distribution of calmodulin, calretinin, calbindin-D28k and neurocalcin during
      rat main olfactory bulb development. From postnatal day 1 (P1) we observed in the
      olfactory nerve layer a thin external bundle containing calbindin and calretinin
      whereas calmodulin was present in a large internal bundle. In tufted cells,
      neurocalcin immunoreactivity was detected at P10 and increased until P20. In
      mitral cells calmodulin was intensively immunoreactive at P1 but decreased during
      development to disappear at adulthood whereas calretinin was weakly labelled at
      P1 but raised in intensity until P20. In granule cells calbindin-D28k and
      calretinin were detected from P1. Giant neurons were positive for both calretinin
      and calbindin-D28k from postnatal day 20.

PMID- 7586510
TI  - National Cholesterol Education Program recommendations for measurement of low
      density lipoprotein cholesterol: executive summary. The National Cholesterol
      Education Program Working Group on Lipoprotein Measurement.

PMID- 7586511
TI  - National Cholesterol Education Program recommendations for triglyceride
      measurement: executive summary. The National Cholesterol Education Program
      Working Group on Lipoprotein Measurement.

PMID- 7586512
TI  - National Cholesterol Education Program recommendations for measurement of high
      density lipoprotein cholesterol: executive summary. The National Cholesterol
      Education Program Working Group on Lipoprotein Measurement.

PMID- 7586514
TI  - Measurement of a more stable region of osteocalcin in serum by ELISA with two
      monoclonal antibodies.
AB  - Intact human osteocalcin purified from femoral bones as well as tryptic fragments
      of the intact molecule [amino acids (aa) 1-19, 20-43, and 45-49] were used to
      raise and screen monoclonal antibodies (MAbs). A two-site ELISA for measurement
      of human osteocalcin in serum was developed with use of these MAbs. A MAb
      recognizing midregion human osteocalcin (aa20-43) was used as capture antibody,
      and an NH2 terminus (aa7-19)-specific peroxidase-conjugated MAb was used for
      detection. Human osteocalcin obtained from bone was used for calibration, and
      parallelism was observed for osteocalcin from serum samples, NH2-terminal
      midfragments (aa1-43), and synthetic human osteocalcin. Both inter- and
      intraassay variations were < 7%. Serum osteocalcin in healthy premenopausal women
      (n = 49) was 18.3 +/- 4.2 micrograms/L (mean +/- SD) and 28.6 +/- 9.7
      micrograms/L in early postmenopausal women (n = 114). The mean serum
      concentration (n = 10) decreased by 10% after 7 days of storage at 4 degrees C,
      whereas the concentration of intact human osteocalcin was reduced 63%. The N-MID
      ELISA and an IRMA measuring intact human osteocalcin were used to monitor the
      effect of hormone replacement therapy in a retrospective study. A significant
      decrease to the premenopausal concentration was detected only in the N-MID ELISA.

PMID- 7586513
TI  - Are reference intervals for carboxyhemoglobin appropriate? A survey of Boston
      area laboratories.
AB  - CO is a leading cause of poisoning deaths in the US today. Treating physicians
      use the carboxyhemoglobin (COHb) % saturation to guide the diagnosis and
      treatment of CO intoxication. We conducted a telephone survey of hospitals and
      laboratories in the Boston area, focusing on methodology for COHb determination
      and accompanying COHb reference intervals. Among 130 facilities, 23 (18%) provide
      COHb analysis. All facilities that perform the COHb test utilize dedicated
      multiwave-length photometry. Reference intervals for COHb varied widely among
      facilities. Eight of 21 (38%) facilities give unacceptably high "normal
      intervals" for nonsmokers when compared with values available in the literature.
      Thirteen of 20 (65%) use reference intervals for smokers that are too low, and 3
      of 20 (15%) use values that are too high. These reference values provided by the
      testing facilities may be misleading to the ordering physicians unfamiliar with
      background COHb saturations. This may lead to misdiagnoses, false reassurances,
      and perhaps less aggressive treatment than might be warranted. The results of
      this study argue for wider adoption of COHb reference intervals supported by the
      current literature.

PMID- 7586515
TI  - Intestinal strontium absorption: from bioavailability to validation of a simple
      test representative for intestinal calcium absorption.
AB  - Calcium absorption tests have rarely been validated for being representative for
      absolute bioavailability (true absorption) or for intraindividual variation.
      Therefore, we investigated the reproducibility of the absolute bioavailability of
      strontium chloride, a marker for intestinal calcium absorption, in healthy male
      volunteers (n = 8) by measuring the area under the plasma strontium concentration
      time curve after oral and intravenous administration of strontium. Subsequently,
      we selected a simple test variable as being representative of absolute
      bioavailability. The mean absolute bioavailability (+/- SD) was 25% +/- 7%. The
      best test variable appeared to be the fractional absorption at 240 min (Fc240)
      after oral intake, which demonstrated the highest correlation with absolute
      bioavailability (r = 0.66). The intraindividual variations of the data for this
      variable and for the absolute bioavailability are similar to those described for
      various absorption tests based on the use of calcium isotopes. Thus, the Fc240 of
      strontium offers the potential of a simple clinical test for use as a measure of
      intestinal calcium absorption and its modulation.

PMID- 7586516
TI  - Transferability of blood lead determinations by furnace atomic absorption
      spectrophotometry and continuum background correction.
AB  - We have examined and proved feasible the transfer of a method for blood lead
      determination, developed and optimized for a Zeeman-corrected instrument, to a
      continuum-corrected furnace atomic absorption spectrophotometer. Numerous
      reference materials analyzed with the continuum-corrected instrument gave results
      within 10 micrograms/L (0.05 mumol/L) at low values and varied by < 6% at values
      > 200 micrograms/L (0.97 mumol/L). Forty-four routine human blood specimens were
      analyzed by the same method with both continuum- and Zeeman-corrected
      instrumentation, and gave results that agreed within about the same limits as
      found with reference materials. The day-to-day precision was about 1/5 the
      accuracy results. The detection limit was approximately 5 micrograms/L (0.025
      mumol/L).

PMID- 7586517
TI  - Highly sensitive and specific HPLC with fluorometric detection for determination
      of plasma epinephrine and norepinephrine applied to kinetic studies in humans.
AB  - An HPLC separation method combined with fluorometric detection was extended to
      enable simultaneous assessment of plasma 3H-labeled and endogenous epinephrine
      (E) and norepinephrine (NE). Forearm fractional extraction (FFE) of 3H-labeled E
      and NE and of endogenous E was measured in 40 healthy volunteers who were
      receiving a continuous infusion of 3H-labeled E and NE. Concentrations of
      arterial and venous E were 26.8 +/- 1.95 (mean +/- SE) and 6.8 +/- 0.75 ng/L,
      respectively. Arterial and venous NE and dopamine (DA) were also measured, with
      respective values of 140.7 +/- 8.5 and 192.1 +/- 15.1 for NE, and 13.1 +/- 0.78
      and 11.3 +/- 0.70 ng/L for DA. The FFE of 3H-labeled E was slightly but
      significantly higher (0.790 +/- 0.016) than the that of either 3H-labeled NE or
      endogenous E (0.748 +/- 0.0146 and 0.745 +/- 0.0185, respectively; P < 0.001),
      the correlations being highly significant (r = 0.80, P < 0.001) in both cases.
      The small difference between the FFE of E and of 3H-labeled E allows the
      calculation of the apparent spillover of E. However, this spillover was
      negligible compared with forearm NE spillover (0.0112 +/- 0.0031 vs 1.369 +/-
      0.128 ng/L per minute. The high sensitivity of this measurement of venous E
      widens the possibilities for studying E kinetics under physiological conditions.

PMID- 7586518
TI  - Direct solid-phase sequence analysis of the human p53 gene by use of multiplex
      polymerase chain reaction and alpha-thiotriphosphate nucleotides.
AB  - Among the candidate cancer-prognostic genes is the p53 tumor suppressor gene,
      which, when mutated, plays an important role in the development of many types of
      cancers. To facilitate robust large-scale DNA analysis of microdissected tumor
      biopsies, we describe a multiplex/nested PCR approach for a simultaneous outer
      amplification of exons 4-9 of the human p53 gene with parallel amplification of
      the HLA-DQB1 locus, involving a total of 14 primers. This approach reduces the
      required number of cells for analysis and avoids any variation in the
      amplifications of the individual p53 exons during the common outer amplification
      step. The HLA sequencing allows sample identification because the DQB1 locus is
      highly polymorphic and is thereby patient-specific. The p53 and HLA amplicons are
      analyzed by solid-phase sequencing in a semiautomated format. To improve the DNA
      sequence quality, we used 2'-deoxyribonucleoside 5'-O-1-thiotriphosphates in the
      sequencing reactions.

PMID- 7586519
TI  - Identification and quantification of intermediates of unsaturated fatty acid
      metabolism in plasma of patients with fatty acid oxidation disorders.
AB  - The free fatty acid and total fatty acid profiles in plasma of nine patients with
      medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, two with very-long-chain
      acyl-CoA dehydrogenase (VLCAD) deficiency and two with mild-type multiple acyl
      CoA dehydrogenase (MAD-m) deficiency, were analyzed by gas chromatography-mass
      spectrometry. In the plasma of patients with MCAD deficiency we found increases
      of octanoic acid (8:0), decanoic acid (10:0), 4-decenoic acid (10:1 omega 6), and
      4,7-decadienoic acid (10:2 omega 3), all present almost exclusively in free form.
      The patients with VLCAD deficiency showed increases of mainly 5-tetradecenoic
      acid (14:1 omega 9) and to a minor extent 5-dodecenoic acid (12:1 omega 7), 5,8
      tetradecadienoic acid (14:2 omega 6), and 7,10-hexadecadienoic acid (16:2 omega
      6), in both the free and esterified fatty acid fraction. The MAD-m patients
      showed variable increases of all the unusual fatty acids present in MCAD- and
      VLCAD-deficient plasma. The 14:1 omega 9, 14:2 omega 6, and 16:2 omega 6 fatty
      acids were present mainly in the esterified form. Measurement of these fatty
      acids in plasma by the relatively simple method presented here provides a
      sensitive and specific aid in the diagnosis of acyl-CoA dehydrogenase deficiency
      disorders.

PMID- 7586520
TI  - Subclass typing of IgG paraproteins by immunofixation electrophoresis.
AB  - We present a simple method for subclass typing of IgG paraproteins, with which we
      have demonstrated a large number of paraproteins that were undetected by
      conventional immunofixation techniques. The types and distribution of IgG
      subclass paraproteins were analyzed in 92 human sera in which IgG paraproteins
      had been demonstrated. The IgG subclass paraproteins were separated by agarose
      gel electrophoresis rapidly and simply and then typed with the use of sheep anti
      human monospecific IgG1-IgG4 antibodies. In 24 of the sera analyzed, IgG subclass
      typing revealed 25 additional monoclonal bands that were not detected by
      conventional immunofixation electrophoresis with anti-IgG antisera. Most of these
      belonged to a different subclass type. The overall subclass frequencies were 68%
      IgG1, 13% IgG2, 16% IgG3, and 3% IgG4. The distribution of paraprotein
      subclasses, however, was different in monoclonal gammopathies of undetermined
      significance in which more IgG3 was shown, whereas in non-Hodgkin lymphomas the
      number of IgG2 paraproteins was greater than expected; this finding may have
      diagnostic and prognostic significance.

PMID- 7586521
TI  - Free and complexed prostate-specific antigen (PSA): in vitro stability, epitope
      map, and development of immunofluorometric assays for specific and sensitive
      detection of free PSA and PSA-alpha 1-antichymotrypsin complex.
AB  - Generation of 15 monoclonal antibodies (MAbs) allowed construction of epitope
      maps and specific two-site immunofluorometric assays for free prostate-specific
      antigen (PSA) and PSA complexed with alpha 1-antichymotrypsin (ACT). Close
      correlation of PSA concentrations obtained with the use of different assays of
      free PSA suggested extensive similarity in immunodetection of free PSA in serum.
      Assays of the PSA-ACT complex overestimated the concentration of PSA-ACT in serum
      because of nonspecific adsorbance of ACT or cathepsin G-complexed ACT to the
      solid phase. This interference was substantially decreased in the presence of
      heparin. In studying the stability of purified PSA and PSA-ACT complexes formed
      in vitro, we found that the free PSA was stable during storage for 4 weeks at 35
      degrees C, whereas PSA-ACT complexes largely dissociated in these conditions. The
      instability of PSA-ACT complexes was counteracted by storage at low temperatures,
      by adjusting the pH of the storage buffer between 6.8 and 7.4, and through
      addition of 100-1000-fold molar excess of native ACT. The ease of calibration and
      the accuracy of free PSA assays in comparison with assays of the PSA-ACT complex
      suggest that measurements of free to total PSA most accurately reflect the
      inverse of the proportion of PSA complexed to ACT in serum.

PMID- 7586522
TI  - Biochemical markers of bone turnover in patients with metastatic bone disease.
AB  - Several biochemical markers of bone formation and bone resorption have recently
      been developed. These markers have been evaluated for clinical utility in
      patients with metabolic bone disease, including Paget disease and osteoporosis,
      and for their potential use in cancer patients whose disease has metastasized to
      bone. We have evaluated seven markers of bone turnover in the plasma and urine of
      94 patients with newly diagnosed or progressive malignancy with and without
      clinical evidence of bone metastases. As determined by a positive bone scan and
      (or) bone survey, 30 patients had metastases to bone; 51 patients had metastatic
      cancer without overt bony involvement; and 13 patients had local disease without
      bone metastases. To evaluate the predictive value of these markers in the
      metastatic population, we utilized a "Z-score" and logistic regression analysis
      to distinguish patients with documented bone metastatic disease from those
      patients without clinical evidence of bone metastases. The higher the Z-score,
      the better the marker predicts the presence of bone metastases. With this
      statistical approach, urine N-telopeptide measurements had the highest Z-score
      and the most significant association with the probability of bone metastases.
      Urine deoxypyridinoline was the second most predictive marker of bone metastases.
      Thus, biochemical markers of bone resorption might be of use to predict the
      presence of bone metastases in cancer patients and to monitor the efficacy of
      antiresorptive therapy in patients treated for metastatic bone disease.

PMID- 7586524
TI  - Diagnosis of premature rupture of membranes with an improved alpha-fetoprotein
      monoclonal antibody kit.
AB  - We developed a new kit for detecting alpha-fetoprotein (AFP) in leaked amniotic
      fluid (Eur J Obstet Gynecol Reprod Biol 1995;58:67-72). Later, we developed an
      improved AFP kit utilizing the same AFP monoclonal antibody. We compared this
      improved AFP test with the nitrazine test for 137 patients. The nitrazine test
      correctly diagnosed 62.1% of the cases, but the improved AFP kit diagnosed 98.0%
      for < 37 weeks of gestation (P < 0.001). The nitrazine test showed a specificity
      of 58.3%, whereas the AFP kit showed a 100% rate for detecting > or = 37 weeks of
      gestation (P < 0.01). The reaction time with the AFP kit is 90 s. This study has
      confirmed a high clinical efficacy of the improved AFP test kit as a method of
      diagnosis of premature rupture of fetal membranes.

PMID- 7586523
TI  - Generation and characterization of monoclonal antibodies to human type-5 tartrate
      resistant acid phosphatase: development of a specific immunoassay of the
      isoenzyme in serum.
AB  - We have characterized four monoclonal antibodies (mAbs) to the purple ("tartrate
      resistant," band 5) acid phosphatase of the human osteoclast (TRAP) and used
      these to develop a specific serum immunoassay. All four mAbs are of high affinity
      (Ka = 1-5 x 10(8) L/mol) with a very fast Kassoc (0.2-2.0 x 10(5) L mol-1 s-1)
      and a moderate Kdissoc (1-3 x 10(-3) s). Two of the mAbs were selected to develop
      a time-resolved fluorescence immunoassay to measure serum concentrations of TRAP.
      The mean serum immunoreactive TRAP in a group of healthy premenopausal women and
      men was 3.7 +/- 1.8 micrograms/L (mean +/- SD) and 3.5 +/- 1.6 micrograms/L,
      respectively. Significantly higher concentrations of TRAP were found in
      postmenopausal women (6.3 +/- 2.3 micrograms/L) and in eight patients with
      Gaucher disease (19.3 +/- 4.7 micrograms/L). Further studies are required to
      investigate the value of serum TRAP as a marker of bone resorption.

PMID- 7586525
TI  - Serum bilirubin and risk of ischemic heart disease in middle-aged British men.
AB  - The possibility that low concentrations of serum bilirubin may be associated with
      increased risk of ischemic heart disease has been examined in a prospective study
      of 7685 middle-aged British men. During 11.5 years there were 737 major ischemic
      heart disease (IHD) events. A U-shaped relationship was observed between serum
      bilirubin and risk of IHD. Low bilirubin was associated with several
      cardiovascular risk factors, in particular smoking, low concentrations of high
      density lipoprotein cholesterol, low forced expiratory volume in 1 s, and low
      serum albumin. The U-shaped relationship persisted even after adjusting for
      several risk factors. Compared with men in the lowest fifth of the distribution
      (bilirubin < 7 mumol/L), those in the middle range (8-9 mumol/L) showed a 30%
      reduction in relative risk [RR = 0.68 (95% confidence intervals 0.51-0.89)] in
      IHD, whereas men in the top fifth (> 12 mumol/L) showed similar risk to the
      lowest fifth [RR = 0.99 (95% confidence intervals 0.73-1.34)], which persisted
      after exclusion of men with bilirubin > 17 mumol/L. The significance of this U
      shaped relationship is unclear, but it could be interpreted as support for the
      role of endogenous antioxidants in the etiology of IHD.

PMID- 7586526
TI  - Blood and plasma glutathione measured in healthy subjects by HPLC: relation to
      sex, aging, biological variables, and life habits.
AB  - We report an HPLC method for measuring the concentrations of reduced (GSH) and
      total (GSHt) free glutathione in human plasma and whole blood. The
      chromatographic step was coupled with a postcolumn derivatization reaction and
      fluorometric detection. The linear range was 0.81-13.02 mumol/L, and the
      detection limit was 0.13 mumol/L. In healthy adults (ages 18-73 years), mean
      concentrations were 941 +/- 155 mumol/L for GSHt and 849 +/- 63 mumol/L for GSH
      in blood (107 men, 94 women), and 3.39 +/- 1.04 mumol/L for GSH in plasma (66
      men, 58 women). Blood GSHt but not GSH was significantly lower in children (32
      boys, 32 girls: 872 +/- 157 mumol/L) than in adults. Blood GSHt and GSH appeared
      to be correlated positively with the number of cigarettes smoked per day and the
      regular practice of physical exercise, and negatively with alcohol abstinence. We
      observed positive correlations between blood GSHt and cholesterol and calcium
      concentrations, and between blood GSH and cholesterol concentration.

PMID- 7586528
TI  - Composition of interstitial fluid.
AB  - In several previous experiments to determine the composition of interstitial
      fluid, the results varied depending on the collecting technique, and the
      electrolyte concentrations differed from those of a hypothetical ultrafiltrate of
      plasma. In our approach, since a change of position from standing to supine is
      accompanied by hemodilution with interstitial fluid, we used the changes in
      hematocrit and composition of plasma in 20 subjects before and after lying down
      to calculate the composition of added interstitial fluid. The estimated protein
      concentration was 20.6 g/L, and the concentrations of total calcium and magnesium
      were low, in accord with a lower concentration of protein-bound calcium and
      magnesium. The activity of free cations was also lower, in agreement with a
      Donnan equilibrium potential of 1 mV across the endothelium. The concentration of
      leukocytes and platelets decreased according to the hemodilution, implying no
      escape or mobilization of these elements.

PMID- 7586527
TI  - Citrate in urine determined with a new citrate lyase method.
AB  - An enzyme-spectrophotometric method to determine citrate in biological fluids is
      proposed, based on citrate lyase-catalyzed and phenylhydrazine reactions. The
      enzyme converts citrate into oxaloacetate, which, in the presence of
      phenylhydrazine, is transformed into the corresponding phenylhydrazone. The
      ultraviolet-absorbing product is determined by absorbance measurement at 330 nm.
      The method is more precise and twice as sensitive as the traditional citrate
      lyase method and, because it does not require the use of additional enzymes and
      coenzymes, is cheaper and simpler. Mean analytical recovery of citrate averaged
      100.7% +/- 2.2%, imprecision (CV) of the assay for citrate at 0.96 mmol/L (urine)
      was 2.0%, and the lower limit of quantification was 0.08 mmol/L. Results
      correlated well with those by both ion-chromatographic and traditional citrate
      lyase methods.

PMID- 7586530
TI  - Detection of glutamic acid decarboxylase autoantibodies with the varelisa ELISA.

PMID- 7586531
TI  - Single test for two hereditary neuropathies, CMT1A and HNPP.

PMID- 7586529
TI  - Cholesterol content of circulating immune complexes in patients with coronary
      stenosis and subjects without evidence of atherosclerosis.
AB  - The biological variation factors for cholesterol in circulating immune complexes
      (CIC-cholesterol) were studied in 941 unselected supposedly healthy volunteers,
      ages 4 to 78 years. We found a complex effect of age, including the existence of
      two peaks of CIC-cholesterol, one in males between 11 and 14 years and in females
      between 11 and 30 years, and in both sexes another peak between 41 and 60 years,
      and in both sexes a decrease between 31 and 40 years. By use of multiple
      regression analysis and after adjustment for age, CIC-cholesterol was positively
      related to plasma cholesterol concentration and leukocyte count, values being
      lower in females than in males and among subjects taking anti-inflammatory drugs.
      In addition, CIC-cholesterol was measured in 76 coronary angiography patients and
      in 100 supposedly healthy controls, ages 30 to 77 years. We noticed a significant
      increase (P < or = 0.05) of CIC-cholesterol when patients were affected by
      coronary stenosis between 20% and 50% (71.8 +/- 52.5 mumol/L vs 46.2 +/- 45.9
      mumol/L in controls), but this was less pronounced in those with > 50% of
      obstruction (58.9 +/- 54.3 mumol/L); however, serum total cholesterol was not
      modified or even surprisingly slightly decreased in the coronary angiography
      individuals. Nevertheless, an important overlap of values in controls and
      patients makes questionable the usefulness of this variable in clinical practice.

PMID- 7586533
TI  - Point-of-care glucose testing: cost savings and ease of use with the Ames
      Glucometer Elite.

PMID- 7586532
TI  - Singleton vs duplicate prostate-specific antigen measurements.

PMID- 7586534
TI  - Four automated random-access immunoassay analyzers evaluated for thyroid function
      testing.

PMID- 7586535
TI  - Modified sample-cup holder improves work flow in immulite immunoassay system.

PMID- 7586536
TI  - Analysis of carbon disulfide and carbonyl sulfide in blood subject to
      interference from the same components from rubber stoppers.

PMID- 7586537
TI  - Difficulties in analysis of CA 125 in diluted samples.

PMID- 7586538
TI  - Modification of malondialdehyde concentration by administration of protamine
      sulfate.

PMID- 7586539
TI  - Increased urine chromium excretion in normal pregnancy.

PMID- 7586540
TI  - Rapid screening of PSA: evaluation of an immunochemical membrane strip test.

PMID- 7586541
TI  - Skeletal alkaline phosphatase activity in serum.

PMID- 7586542
TI  - Fluorescence in situ hybridization: powerful molecular tool for cancer prognosis.
AB  - We review several aspects of fluorescence in situ hybridization (FISH) technology
      that demonstrate its breadth and power in detecting and monitoring genetic
      abnormalities associated with cancers. The clinical utility of FISH in disease
      management is demonstrated in several examples, including trisomy 8 detection
      with high specificity and sensitivity in patients with myeloid leukemias; trisomy
      12 detection with higher efficiency than conventional cytogenetics in patients
      with chronic lymphocytic leukemia; assessment of engraftment success, chimerism,
      and relapse in opposite sex bone marrow transplantation; and correlation of
      trisomy 7 with survival time in patients with prostate tumors. Advances in FISH
      technology include multicolor analyses, which permit the simultaneous detection
      of several genetic abnormalities by using cohybridization of probes labeled with
      several fluorescent labels or label combinations, and comparative genomic
      hybridization, a relatively new method whereby a single hybridization can reveal
      aberrations across the entire genome.

PMID- 7586543
TI  - Monoclonal antibody assay for measuring bone-specific alkaline phosphatase
      activity in serum.
AB  - Alkaline phosphatase (ALP) is present in human serum in the form of several
      isoenzymes. The two major circulating ALP isoenzymes, bone and liver, are
      difficult to distinguish because they are the products of a single gene and
      differ only by posttranslational glycosylation. Quantitative measurement of bone
      ALP (BAP) activity in serum can provide an index for the rate of bone formation.
      Furthermore, increased BAP activity in serum is indicative of bone disorders. We
      describe a method in which serum samples are added to a microtiter plate coated
      with monoclonal anti-BAP antibody and incubated 3 h at room temperature. After
      the unbound materials are washed off, the bound BAP activity is measured by
      adding p-nitrophenyl phosphate substrate. The assay demonstrated no cross
      reactivity to intestinal or placental ALP and only 3-8% cross-reactivity to liver
      ALP. The intraassay (n = 21) CVs were 3.9-5.9%, and interassay (n = 8) CVs were
      4.4-7.0%. Comparisons of the assay (y) with an IRMA (x) and a wheat germ
      agglutinin precipitation method (x') gave regression equations of y = 1.32x-6.4,
      r = 0.99, and y = 1.41x' + 4.8, r = 0.99. The assay detected increased BAP in
      sera from patients with osteoporosis, Paget disease, osteomalacia, or primary
      hyperparathyroidism.

PMID- 7586544
TI  - Purification and characterization of different molecular forms of prostate
      specific antigen in human seminal fluid.
AB  - We have developed a new procedure for purifying prostate-specific antigen (PSA)
      from human seminal fluid. The method is based on ammonium sulfate precipitation,
      hydrophobic interaction chromatography, gel filtration, and anion-exchange
      chromatography. It can be completed within 2 days with a recovery of intact PSA
      of 30%. By anion-exchange chromatography, five isoforms of PSA (A, B, C, D, and
      E) can be separated. The major form (PSA-B) consists of the intact enzyme, as
      shown by the occurrence of only one band of 33 kDa in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under reducing or nonreducing conditions, and
      by amino acid sequencing, which reveals only one amino-terminal sequence
      corresponding to the reported amino-terminal sequence of intact PSA. The specific
      absorbance of 1 g/L PSA-B at 280 nm was 1.61, and 80% of the PSA-B formed a
      complex with alpha 1-antichymotrypsin, indicating that it is enzymatically
      active. Three cleaved forms of PSA with different nicking sites and low enzymatic
      activity were separated from intact PSA by ion-exchange chromatography. In
      addition, we isolated a glycosylation variant, PSA-A, which showed a higher
      isoelectric point (pI = 7.2) than PSA-B (pI = 6.9) but similar enzymatic
      activity; this form accounts for 5-10% of total PSA. After treatment with
      sialidase, PSA-A and B had the same isoelectric point value (pI = 7.7).

PMID- 7586545
TI  - Serum catalase as marker of graft-vs-host disease in allogeneic bone marrow
      transplant recipients: pilot study.
AB  - We evaluated the efficacies of serum catalase (CAT), 5'-nucleotidase (5'NT), and
      tumor necrosis factor-alpha (TNF) as diagnostic markers of acute graft-vs-host
      disease (GVHD) in 28 allogeneic bone marrow transplant recipients by comparing
      their abilities to discriminate between GVHD-related and non-GVHD-related
      complications. Mean peak serum CAT concentrations for patients with GVHD-related
      complications (n = 17) were about fivefold higher than concentrations in patients
      with non-GVHD-related complications (n = 25; P = 0.003), whereas the mean peak
      concentrations of serum 5'NT and TNF were not substantially different. Similarly,
      the sensitivity and specificity of serum CAT (100% and 88%, respectively) for use
      as a diagnostic marker of GVHD were much better than those of serum 5'NT (88% and
      24%, respectively) or serum TNF (65% and 4%, respectively). Receiver-operating
      characteristic plots of all possible sensitivity-specificity pairs obtained over
      the whole range of results also showed that serum CAT has the best diagnostic
      accuracy. Low specificities of serum TNF and 5'NT were caused mainly by their
      increase in septicemia, fungal infection, and veno-occlusive disease and after
      the use of granulocyte-macrophage colony-stimulating factor to stimulate donor
      cell engraftment. Serum CAT may prove to be a rapid and relatively noninvasive
      test for the diagnosis of acute GVHD.

PMID- 7586546
TI  - Reliability of salivary testosterone measurements: a multicenter evaluation.
AB  - The reliability of salivary testosterone assays was evaluated by nine
      laboratories in four countries. Each laboratory used its own RIA procedures to
      assay samples from a set of 100 male and 100 female subjects. Agreement among the
      laboratories on mean scores was within the range reported by Read (Ann N Y Acad
      Sci 1993; 694: 161-76). Overall agreement on individual scores, as indicated by
      the intraclass correlation coefficient computed within subjects across
      laboratories, was r = 0.87 for men and r = 0.78 for women. Mean agreement between
      each laboratory and the combined set of all other laboratories (via Fisher's Z
      transformation) was r = 0.61 for men and r = 0.58 for women. We take these latter
      values to be the best estimates of the average reliability of laboratories in
      their ordering of individual samples.

PMID- 7586547
TI  - Relation between cathepsin D expression and other prognostic factors in breast
      carcinomas.
AB  - We evaluated cathepsin D concentrations in 318 breast carcinoma specimens with a
      standardized IRMA and established distribution values of 5.9-217.8 nmol/g (median
      51.8). Concentrations of cathepsin D did not correlate with age or with
      concentrations of HER-2/neu oncoprotein, estrogen receptor, or epidermal growth
      factor receptors. A significant correlation was observed between cathepsin D and
      progestin receptor (P = 0.009), but only in postmenopausal patients. In our role
      as a National Reference Laboratory for conducting interlaboratory comparisons of
      tumor markers, we evaluated cathepsin D assay proficiency by using control
      samples with intra- and interassay CVs of 2-8% and 10-13%, respectively. Human
      reference specimens containing known quantities of cathepsin D were developed to
      facilitate standardized testing. The IRMA procedure and the use of quality
      assurance samples permits evaluation of the clinical significance of cathepsin D
      in human breast cancer trials.

PMID- 7586549
TI  - High-throughput method for determination of apolipoprotein E genotypes with use
      of restriction digestion analysis by microplate array diagonal gel
      electrophoresis.
AB  - Molecular epidemiological research has identified the association of a common
      apolipoprotein E (apo E) isoform (E4 as opposed to E3), with risk both of
      coronary artery disease and of Alzheimer dementia. In addition, the role of apo E
      genotype (usually E2/E2) in Type III hyperlipidemia is well known. However, both
      for diagnostic and research purposes, apo E genotyping is cumbersome. The
      preferred approach is electrophoretic sizing of restriction digestion fragments,
      enabling simultaneous analysis of the two codons (112 and 158) that represent the
      six common genotypes (E2/E2; E2/E3; E2/E4; E3/E3; E3/E4; E4/E4). However, the
      consequent demands of high-yield PCR, high-resolution, high-throughput
      electrophoresis, and sufficient detection sensitivity have left shortfalls in
      published protocols. In conjunction with a high-throughput electrophoresis system
      we described recently, microplate array diagonal gel electrophoresis (MADGE), we
      have constructed extensively optimized, simplified protocols for DNA isolation
      from mouthwash samples for PCR setup and high-yield PCR, for restriction
      digestion, and for subsequent MADGE gel image analysis. The integral system
      enables one worker to readily undertake apo E genotyping of as many as hundreds
      of DNA samples per day, without special equipment.

PMID- 7586548
TI  - Different responses of biochemical markers of bone resorption to bisphosphonate
      therapy in Paget disease.
AB  - We examined the response of different biochemical markers of bone resorption to
      bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget
      disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and
      free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds,
      immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage
      (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase
      (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP
      showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and 
      6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides
      (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The
      response was somewhat greater for TPyds than for FPyds. We conclude that: (a)
      ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b)
      oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine
      show a somewhat greater response to therapy than do FPyds and may be more
      sensitive indicators of bone resorption; and (c) as yet no evidence suggests that
      these markers are substantially better predictors of the clinical response to
      therapy than serum total alkaline phosphatase or urinary OHP. There are several
      problems with the interpretation of these measurements in Paget disease, and the
      clinical utility of these measurements remains uncertain.

PMID- 7586550
TI  - Improved RNase protection assay for quantifying LDL-receptor mRNA; estimation of
      analytical imprecision and biological variance in peripheral blood mononuclear
      cells.
AB  - We have improved the protocol for RNA quantification by using RNase protection.
      Instead of precipitation and extraction with phenol and chloroform, we use a
      faster and more reliable precipitation based on guanidinium thiocyanate (GdSCN).
      The internal standard is produced by in vitro transcription of a DNA template
      constructed so as to allow simultaneous detection of the in vitro transcript and
      the low-density lipoprotein receptor (LDLR) mRNA by use of the same probe and
      hybridization. Addition of this internal standard at the step for RNA isolation
      reduced the analytical imprecision from 40.8% to 19.3%. Estimates of the within-
      and between-subject biological variations of the LDLR mRNA content in peripheral
      blood mononuclear cells (PBMCs) isolated from healthy volunteers were 21.5% and
      13.6%, respectively, and the analytical imprecision was 22.6%. The mean content
      of LDLR mRNA in PBMCs from healthy individuals was 0.78 copies per cell.

PMID- 7586551
TI  - False-positive and false-negative rates in meconium drug testing.
AB  - To determine the number of false-negative results produced by inefficient
      extraction of drugs from meconium, three published procedures were compared by
      using previously confirmed positive and negative meconium specimens. The methods
      were not equivalent in their ability to extract drugs from the matrix. To
      determine the number of false positives reported by the use of screen-only
      (unconfirmed) results, 535 screen-positive meconium specimens were subjects to
      confirmation by gas chromatography-mass spectrometry. Fifty-seven percent of the
      samples were confirmed positive for one or more of the drugs under investigation,
      showing that a false-positive rate as high as 43% may exist when unconfirmed
      screening results are used.

PMID- 7586553
TI  - Effect of aging on susceptibility of low-density lipoproteins to oxidation.
AB  - According to the Adult Treatment Panel of the National Cholesterol Education
      Program, age is a major risk factor for heart disease. To assess the relation
      between age and LDL oxidizability, we studied copper-mediated LDL oxidation in 13
      healthy elderly subjects (> 59 years) and 13 sex-matched healthy young controls
      (< 30 years). Total and LDL-cholesterol concentrations were increased in elderly
      subjects. The time course of copper-mediated LDL oxidation showed no significant
      differences between the two groups as assessed by formation of conjugated dienes,
      lipid peroxides, and apolipoprotein B fluorescence. Kinetics of LDL oxidation as
      quantified by lag time, oxidation rate, and maximal oxidation were not
      significantly different between the elderly and young groups. Although the
      concentrations of 16:0, 18:0, 18:1, 18:3, and 20:4 and total polyunsaturated
      fatty acids were significantly higher in the elderly group, LDL fatty acid
      concentrations were similar in both groups. Lipid-standardized alpha-tocopherol,
      beta-carotene, and ascorbate concentrations were not significantly different
      between the two groups. The findings of the present study suggest that in the
      healthy elderly, LDL oxidation may not be a crucial mediator for atherogenesis.

PMID- 7586552
TI  - Proposed confirmatory procedure for detecting 5 alpha-dihydrotestosterone doping
      in male athletes.
AB  - Currently, there is no recommended confirmatory procedure for detecting doping
      with the anabolic steroid 5 alpha-dihydrotestosterone (DHT) in sportsmen. To
      develop a method, we determined ratios of hormone concentrations in urine from
      120 healthy men and used these to set discrimination limits. These limits were
      then applied to results for urine specimens from 10 volunteers given DHT
      percutaneously (125 mg twice daily for 4 days). The ratio of DHT to
      epitestosterone (EpiT) was chosen as the primary marker of DHT administration,
      and ratios of 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha-ADIOL) to EpiT, 5
      alpha-ADIOL to luteinizing hormone, and 5 alpha-ADIOL to 5 beta-androstane-3
      alpha, 17 beta-diol were proposed as secondary markers. To evaluate method
      suitability, we analyzed 194 samples from sports competitors; results for 193
      samples were negative, but the ratios in 1 sample greatly exceeded all the chosen
      limits. In conclusion, we propose that a test scheme based on our recommendations
      be considered for implementation in all Olympic drug-testing laboratories.

PMID- 7586554
TI  - Serum concentrations of apolipoprotein A-I, apolipoprotein B, and lipoprotein(a)
      in a population sample.
AB  - Serum concentrations of apolipoprotein (apo) A-I, apo B, and lipoprotein(a)
      [Lp(a)] were studied with respect to age and sex in a Finnish population sample
      of 575 subjects (286 men and 289 women), ages 27-67 years. Apo A-I and apo B were
      measured with an immunoturbidimetric method calibrated against WHO International
      Reference Materials. Lp(a) was measured by RIA. Apo A-I and apo B concentrations
      were almost normally distributed (apo A-I: mean 1.38 g/L vs median 1.34 g/L for
      men, and 1.58 g/L vs 1.55 g/L for women; apo B: mean 1.21 g/L vs median 1.20 g/L
      for men and 1.09 g/L vs 1.05 g/L for women). The distribution of Lp(a) was
      remarkably skewed (mean 190 mg/L vs median 86 mg/L for men, and 169 mg/L vs 85
      mg/L for women). The 95% intervals for apo A-I were 1.09-1.84 g/L for men and
      1.06-2.28 g/L for women; for apo B, they were 0.63-1.88 g/L and 0.56-1.82 g/L,
      respectively. Apo A-I concentrations appeared to be unrelated to age, whereas apo
      B and Lp(a) concentrations were age-dependent. Cutoff values based on the 90th
      percentile for apo B and the 10th percentile for apo A-I are proposed for
      identifying subjects at increased risk of coronary heart disease.

PMID- 7586555
TI  - AquaLite bioluminescence assay of thyrotropin in serum evaluated.
AB  - We studied a new commercially available thyrotropin (TSH) assay, the AquaLite
      Bioluminescence TSH-Immunoassay (SeaLite Inc.). This assay has a detection limit
      of 0.005 mIU/L and a functional sensitivity of 0.017 mIU/L and meets the
      requirements of a third-generation TSH assay. Using this assay, we measured serum
      TSH in 153 euthyroid individuals and in the following patients: 32 primary
      hypothyroids; 38 primary hyperthyroids; 35 with thyroid cancer receiving
      suppressive therapy with levothyroxine (L-T4); 33 receiving replacement L-T4
      aimed at reaching and maintaining a euthyroid status; 23 with subclinical
      hyperthyroidism; and 52 hospitalized for nonthyroidal illnesses (NTI). The
      AquaLite TSH assay perfectly discriminated hypothyroid and untreated hyperthyroid
      patients from euthyroid subjects and clearly discriminated between overtly and
      mildly hyperthyroid patients. Intermethod comparisons showed that the AquaLite
      and the Nichols assays were more effective than the ACS-180 and the TOSOH assays
      in discriminating among hyperthyroid patients, including patients over-treated
      with L-T4.

PMID- 7586556
TI  - Glycohemoglobin assays evaluated in a large-scale quality-control survey.
AB  - We report the results of a national quality-control survey on glycohemoglobin
      (GHb), monitored in France by the Societe Francaise de Biologie Clinique on
      behalf of the authority of the "Agence du Medicament." A sample of lyophilized
      hemolysate was sent to 3109 laboratories. Results were obtained from 2770
      laboratories. HbA1C, HbA1, and total GHb were measured by 50%, 24%, and 26% of
      the participants, respectively. Of these measurements, 79% of the HbA1C results
      and 76% of the total GHb results, but only 48% of the HbA1 results, were within
      the +/- 20% limits of the indicated target values. Mean values for the hemolysate
      ranged from 8% to 11% for HbA1C, from 7% to 12% for HbA1, and from 11% to 13% for
      total GHb. The interlaboratory CVs ranged from 3% to 20%, according to method
      used. So, methods used for GHb assay, which are based on various principles,
      exhibit very different analytical performances. Nonetheless, this large-scale
      study indicates that some techniques can support transferability of results from
      laboratory to laboratory.

PMID- 7586557
TI  - Analyzer-dependent differences in results for ionized calcium, ionized magnesium,
      sodium, and pH.
AB  - We compared two ion-selective analyzers (AVL 988-4 and NOVA CRT) for determining
      ionized calcium (iCa2+), ionized magnesium (iMg2+), sodium (Na+), and pH in serum
      specimens from healthy and diseased individuals. For assays of three levels of
      protein-based control materials, total imprecision (CV) was < 3% for all analytes
      except iMg2+ (< or = 6.5% on NOVA, and < or = 4.9% on AVL). We found a
      significant difference between the analyzers (P < 0.001) for the mean iMg2+
      concentration in patients but no significant correlation (r = 0.253) between the
      analyzers for iMg2+ in specimens from healthy volunteers, even though the mean
      iMg2+ concentration did not differ significantly between these groups. The
      reference interval (central 95 percentiles) for iMg2+ with AVL (0.44-0.60 mmol/L)
      was contained within that of NOVA (0.39-0.64 mmol/L). The AVL gave higher values
      for iCa2+ (P < 0.001) and lower values for pH (P < 0.001) in specimens from
      normal volunteers and patients. The mean value for Na+ in patients' samples was
      significantly higher by the NOVA (P < 0.01) than by the AVL analyzer. Thus, we
      found significant differences between these two analyzers for all four analytes.

PMID- 7586558
TI  - Calcium ion binding to clinically relevant chemical modifications of human serum
      albumin.
AB  - Calcium binding to glycated, penicilloylated, acetylated, and normal defatted
      human serum albumin as well as to mercapt- and nonmercaptalbumin was studied by
      equilibrium dialysis of radioactive Ca2+. Binding was quantified by five
      Scatchard constants [ni = 1, (i = 1-4) and n5 = 10]. Glycation resulted in
      increased k1- and k2-values and unchanged k3-k5-values, whereas penicilloylation
      increased all five association constants. The increments were greater the more
      pronounced the modification, and the enhancements caused by penicilloylation
      were, for the same degree of modification, greater than those produced by
      glycation. In contrast, acetylation by acetylsalicylate did not affect calcium
      binding. Likewise, binding to mercapt- and nonmercaptalbumin was the same, a
      finding showing that the thiol group of cysteine 34 is not important for calcium
      binding. D-Glucose and penicillin G are known to react with lysine residues of
      albumin, and the enhancement of binding resulting from glycation or
      penicilloylation is probably brought about by unspecific electrostatic effects,
      possibly supplemented by conformational changes of the protein molecule. The
      relative importance of the three domains of human serum albumin for calcium
      binding is discussed.

PMID- 7586559
TI  - Automation of a kinetic method for determining angiotensin-converting enzyme in
      serum.

PMID- 7586560
TI  - Free amino acids in amniotic fluid and the prenatal diagnosis of homocystinuria
      with methylmalonic aciduria.

PMID- 7586562
TI  - Enzymatic activity in glucose-6-phosphate dehydrogenase-normal and -deficient
      neonates measured with a commercial kit.

PMID- 7586561
TI  - OnLine kinetic microparticle immunoassay of cannabinoids, morphine, and
      benzoylecgonine in serum.

PMID- 7586563
TI  - CA 125 determined by three methods in samples from patients with human anti-mouse
      antibodies (HAMA).

PMID- 7586564
TI  - Asymptomatic erythrocyte disorder presenting as increased porphobilinogen
      deaminase and uroporphyrinogen decarboxylase.

PMID- 7586567
TI  - Concentrations of acute-phase proteins in infants.

PMID- 7586566
TI  - Cardiac troponin T in renal disease.

PMID- 7586568
TI  - Colorimetric assessment of smoking status and relative daily nicotine intakes.

PMID- 7586569
TI  - Mild course of cystic fibrosis in an adult with the D1152H mutation.

PMID- 7586565
TI  - Is the Watson-Schwartz screening method for porphobilinogen reliable?

PMID- 7586570
TI  - Highly specific immunoassay for cardiac troponin I assessed in noninfarct
      patients with chronic renal failure or severe polytrauma.

PMID- 7586571
TI  - Identification of the D-enantiomer of 2-hydroxyglutaric acid in glutaric aciduria
      type II.
AB  - We determined the optical isomer of the 2-hydroxyglutaric acid (2HG) that was
      elevated in the urine of five Japanese children with a mild form of glutaric
      aciduria type II (GA2), caused by a deficiency of electron transfer flavoprotein
      (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO). The D- and L-enantiomers of 2HG
      were separated by capillary gas chromatography with a combination of (S)-(+)-2
      octanol derivatization and chromatography on a DB-1 column. The isomer that was
      elevated in GA2 patients was predominantly the D-enantiomer, an observation that
      may serve as an additional marker for the biochemical diagnosis of GA2. D-2HG
      dehydrogenation, but not L-2HG dehydrogenation is apparently blocked in GA2. A
      specific D-2HG dehydrogenase or D-2HG-CoA dehydrogenase may be metabolically
      linked to ETF and ETF-QO in the mitochondria.

PMID- 7586573
TI  - N-methyladrenaline: age-dependent urinary excretion, perinatal organ content and
      relation with 'classical' catecholamines.
AB  - Using high performance liquid chromatography with electrochemical detection we
      determined free dopamine, noradrenaline, adrenaline and N-methyladrenaline in:
      (1) urines from newborns (n = 32), children (n = 45) and adults (n = 19) and (2)
      adrenals, organ of Zuckerkandl, dorsal roots and perirenal brown adipose tissue
      from deceased fetuses (n = 2), very premature (n = 6) and term (n = 2) newborns
      and infants (n = 2). Data from children and adults showed that contributions of
      adrenaline and N-methyladrenaline to the sum of urinary free catecholamines
      increase with age. Relative amounts of adrenaline and N-methyladrenaline
      increased in both adrenal and extra adrenal chromaffin tissues from late
      gestation up to several months of postnatal life. Increase of adrenal N
      methyladrenaline content follows endocrine maturation of the medulla,
      phenylethanolamine-N-methyltransferase induction and subsequent adrenaline
      synthesis. Relative amounts of N-methyladrenaline in extra adrenal chromaffin
      tissue increase in a period that is associated with its regression. Further
      investigations are necessary to elucidate the function and possible clinical
      chemical usefulness of N-methyladrenaline.

PMID- 7586574
TI  - Maternal serum screening for fetal Down's syndrome, a retrospective study.
AB  - A retrospective study of the different biochemical markers used in screening for
      Down's syndrome was carried out on serum from 18,600 women between their 15th and
      18th week of pregnancy. Thirty-two sera were from women with fetal Down's
      syndrome. The retrospective study of these 32 sera involves: (a) the screening of
      the maternal serum concentrations of human chorionic gonadotropin (hCG) and of
      alpha-fetoprotein (AFP); (b) the evaluation of the risk of Down's syndrome when
      screening maternal serum concentrations of hCG alone, then the combination of the
      two markers and finally the maternal serum concentrations of unconjugated estriol
      (uE3). The mean of MOM (multiples of the median) for the pathological sera were
      calculated for hCG (1.91), for AFP (0.63), for the ratio hCG over AFP (3.02) and
      for uE3 (0.72). With the use of hCG alone we estimated a 41% detection rate for
      an amniocentesis rate of 5.3%, whereas when hCG was combined with AFP the
      detection rate approached 65% for an amniocentesis rate of 5.5% at a risk cut-off
      of 1:300. The results of the uE3 determination confirm the validity of this
      marker. The comparison of these results with other retrospective studies shows
      the incidence of different factors in the detection rate such as the choice of
      markers, the age group studied, the modes of calculating the risk and the actual
      cut-off chosen.

PMID- 7586572
TI  - Effect of neurotoxic metal ions in vitro on proteolytic enzyme activities in
      human cerebral cortex.
AB  - In order to develop a clearer understanding of the role of aberrant protein
      turnover in the pathogenesis of neurodegenerative disorders, the effect of a
      series of potentially neurotoxic metal ions on a wide range of proteases
      (lysosomal and cytoplasmic proteinases and peptidases) from human cerebral cortex
      was determined in vitro. The response of lysosomal and cytoplasmic proteases to
      inhibition by metal ion species (0.05-5 mmol/l) was broadly similar; Sr2+, Mg2+,
      Ba2+ or Ca2+ showed little inhibitory effect at any concentration for most
      protease types, whilst Cu2+, Cd2+, Pb2+, Mg2+ or Zn2+ showed a substantial degree
      of inhibition, depending on metal ion concentration and enzyme type. Ca2+
      activated neutral proteinases were no more susceptible to general metal ion
      inhibition than most other protease types. Some proteases showed marked
      activation of activity in the presence of several metal ion species. Both
      lysosomal and cytoplasmic proteases were relatively insensitive to inhibition by
      Al3+, compared with that obtained with other metal ion species. It is of note
      that cathepsin D was particularly resistant to inhibition by most metal ion
      species, whilst pyroglutamyl aminopeptidase was particularly susceptible to
      inhibition by low concentrations of many metal ions. The above data suggest that
      in considering the potential role of neurotoxic metal ions in the pathogenesis of
      neurodegenerative disorders of the CNS (via protease inhibition in the
      intracellular protein degradation pathway), attention should be focused on the
      interactions between a wide range of metal ion species and protease types, rather
      than be restricted to the Al3+/calpain system (as is presently the case in
      Alzheimer's disease research). In particular, the potential role of pyroglutamyl
      aminopeptidase in intracellular protein degradation (in addition to more
      specialized functions such as neurotransmitter processing) and the pathological
      consequences of the susceptibility of this enzyme to inhibition by neurotoxic
      metal ions requires further investigation.

PMID- 7586577
TI  - Serotonin content in human blood platelets is not stable.
AB  - A large variation of platelet serotonin content over short time intervals has
      been shown. This oscillation of platelet serotonin does not result from the
      accumulation of random technical variations, but can be considered as an
      objectively existing phenomenon which might be due to alternation of serotonin
      release and uptake processes in platelet-rich plasma. Sex and age do not
      influence the variation of platelet serotonin.

PMID- 7586575
TI  - Variegate porphyria: diagnostic value of fluorometric scanning of plasma
      porphyrins.
AB  - Variegate porphyria (VP) is a dominantly inherited acute hepatic porphyria
      characterized by a 50% decrease in activity of protoporphyrinogen oxidase (PO)
      which catalyses the last step of heme biosynthesis. In VP families, most of the
      gene carriers are asymptomatic but at risk of developing acute attacks if
      subjected to precipitating factors. Recognition of the carrier status is the
      first step of an efficient preventive care. This could be achieved by measurement
      of PO activity which is a sensitive and specific but tedious method. A specific
      plasma fluorometric emission at 626 nm has been shown in VP patients. Here we
      show that this simple and inexpensive method is specific but poorly sensitive,
      especially in detection of asymptomatic carriers. We conclude that this procedure
      should not replace PO activity measurement in VP family studies.

PMID- 7586576
TI  - Demonstration of induction of erythrocyte inosine monophosphate dehydrogenase
      activity in Ribavirin-treated patients using a high performance liquid
      chromatography linked method.
AB  - The activity of inosine monophosphate dehydrogenase (IMPDH: EC 1.2.1.14) was
      measured in erythrocyte lysates using a non-radiolabelled method linked to
      reversed-phase liquid chromatography (RPLC). The mean activity in erythrocytes
      from healthy controls using this sensitive method was extremely low (mean 85
      pmol/h per mg protein, range 4-183). The elevated erythrocyte IMPDH activity
      reported previously in hypoxanthine-guanine phosphoribosyltransferase (HPRT)
      deficiency was confirmed (mean 234 pmol/h per mg protein). Erythrocyte IMPDH
      activity of patients with other disorders of purine metabolism, or with
      leukaemias and lymphomas, showed no marked difference from controls, except in
      one instance--an immunodeficient child with purine nucleoside phosphorylase (PNP)
      deficiency, treated with Ribavirin, where a 30-fold increase in activity was
      found (2670 pmol/h per mg protein). Investigation of erythrocyte IMPDH in other
      immunodeficient children with normal PNP activity demonstrated that this grossly
      elevated erythrocyte activity was attributable to induction of IMPDH by Ribavirin
      therapy.

PMID- 7586578
TI  - Actions of arachidonic acid on erythrocyte membrane Rb permeability.
AB  - The effects of non-esterified arachidonic acid (AA) on erythrocyte membrane ion
      permeability have been studied using 86Rb flux measurements. [14C]AA was used to
      quantify membrane incorporation of AA and to show AA removal by albumin washing.
      The actions of vitamin E and other antioxidants on the effects of AA were
      examined. Reversible membrane incorporation of 700-2000 nmol AA per ml cells was
      achieved without significant haemolysis or morphological change. AA incorporation
      caused a reversible mean increase in bumetanide-sensitive Rb influx of 34%
      (S.E.M. 4.5, n = 23). This action could be partially prevented by co-incubation
      with vitamin E, but not by Trolox or dithioerythritol. AA incorporation caused an
      irreversible mean increase in residual Rb permeability (bumetanide and ouabain
      insensitive) of 130% (S.E.M. 22, n = 20), associated with a rise in intracellular
      Na and a fall in intracellular K concentrations. This action was also partially
      prevented by co-incubation with vitamin E. The effects of AA incorporation on
      Na,K-ATPase function were difficult to quantify because of the concomitant rises
      in intracellular Na but the data are consistent with approximately 20% inhibition
      of activity. Modulation of membrane ion permeability by AA appears to be
      partially mediated by lipid peroxidation and may have pathophysiological
      significance.

PMID- 7586580
TI  - Rapid degradation of 3,4-dihydroxyphenylalanine in plasma samples containing
      ethylenediaminetetraacetic acid.

PMID- 7586579
TI  - Fasting plasma glucose as a diagnostic indicator of diabetes mellitus.
AB  - Among 233 patients referred for glucose tolerance test (GTT), 36.4% of 129 non
      pregnant subjects were classified as diabetic, compared with only 2.9% of 104
      pregnant subjects. Preliminary screening using a fasting plasma glucose upper cut
      off of 7.0 mmol/l, above which the subject was classified as diabetic and a lower
      one of 4.4 mmol/l, below which he or she was considered normal, would have
      eliminated the need for 30% of GTTs and positively identified 60% of the
      diabetics in the non-pregnant group. Only one patient would have been
      significantly misclassified, possibly owing to inadequate fasting. However,
      little benefit would result from applying an upper cut-off to low-prevalence
      populations such as the pregnant group. Like other recent surveys, this study
      suggests that World Health Organisation diagnostic figures for fasting plasma
      glucose could be revised downwards to 7.0 mmol/l. Conversely, to be fairly
      certain that an individual is not diabetic, fasting plasma glucose must be below
      about 4.4 mmol/l.

PMID- 7586582
TI  - Arterial blood ammonia during orthotopic liver transplantation as an indicator of
      waste elimination by the new liver.

PMID- 7586581
TI  - Effects of urinary macromolecules on the nucleation of calcium oxalate in
      idiopathic stone formers and healthy controls.
AB  - Urinary macromolecules have attracted great interest because of their possible
      role as both promoters and inhibitors of calcium oxalate (CaOx) crystallization
      and it remains unclear whether there is any difference, in their nucleating
      activity, between stone formers and controls. We selected 9 male idiopathic CaOx
      stone formers whose 24-h urines presented no evidence of common urinary stone
      risk factors such as hypercalciuria, hyperoxaluria, hyperuricosuria,
      hypocitraturia, hypomagnesiuria or low glycosaminoglycans excretion and 12 male
      controls (matched for age and body weight) whose 24-h urines did not differ from
      those of stone formers. The study of urinary CaOx nucleation was made in freshly
      voided overnight urines whose biochemical composition was almost identical in the
      two groups. In filtered (0.22 micron) and ultrafiltered (10 kDa) urine we
      performed an oxalate tolerance test to determine the permissible increment of
      oxalate, the oxalate level for nucleation and the permissible increment of CaOx
      relative supersaturation (CaOx RS). In filtered urine from stone formers the
      permissible increment of oxalate was lower than controls (30 +/- 10.2 vs. 46.7 +/
      9.7 mg/l, P = 0.001), the oxalate level for nucleation was lower (64.4 +/- 14.2
      vs. 79.5 +/- 15.6 mg/l, P = 0.035) and the permissible increment of CaOx RS was
      also lower (9.71 +/- 2.59 vs. 13.39 +/- 3.62, P = 0.018). In ultrafiltered urine
      these differences disappeared because the removal of macromolecules in stone
      formers significantly enhanced the oxalate-tolerance values. The difference
      between the change of the oxalate permissible increment of filtered and
      ultrafiltered urine allowed a distinction to be made between stone formers and
      controls that was not feasible in other ways (7.6 +/- 5.3 vs. 3.3 +/- 5.9 mg/l, P
      < 0.0001). The study suggests that, in idiopathic CaOx stone formers free from
      common urinary risk factors of CaOx crystallization, there is an increased
      tendency for CaOx nucleation in urine, which is mediated by macromolecular
      components.

PMID- 7586583
TI  - Free fatty acid analysis in ascitic fluid improves diagnosis in malignant
      abdominal tumors.
AB  - The fasting concentration of free fatty acids (FFA) in the ascitic fluid was
      determined in 14 patients with malignant ascites and in 19 patients with liver
      cirrhosis. In malignant ascites FFA levels were increased more than three times
      when compared with the levels in cirrhotic ascites (5.241 +/- 0.493 vs. 1.558 +/-
      0.170 mumol/ml; P < 0.0001). Palmitic acid was the most representative saturated
      FFA (which together accounted for 2.499 +/- 0.323 vs. 0.833 +/- 0.064 mumol/ml; P
      < 0.0001), while unsaturated FFA (2.741 +/- 0.298 vs. 0.725 +/- 0.111 mumol/ml; P
      < 0.001) were represented, in decreasing order, by oleic, linoleic and
      arachidonic acids. The ratio of unsaturated to saturated FFA was higher in
      neoplastic patients (1.35 +/- 0.29 vs. 0.826 +/- 0.065 P < 0.05). Albumin
      concentration in ascitic fluid of neoplastic patients was 22.44 +/- 1.35 g/l,
      while that of cirrhotic patients was 8.19 +/- 0.32 g/l, P < 0.0001. A close
      relationship (R2 = 95.14%) between albumin concentration in ascitic fluid and
      levels of total FFA was found. These data support the hypothesis that the
      elevation of FFA in ascitic fluid allows discrimination between malignant and non
      malignant ascites.

PMID- 7586584
TI  - Components of biological variation in plasma haptoglobin: relationships to plasma
      fibrinogen and immune variables, including interleukin-6 and its receptor.
AB  - We investigated the components of biological variation, including seasonality, in
      plasma haptoglobin (Hp) levels and the relationships between plasma Hp and
      interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6), sIL-2R, fibrinogen (Fb) and
      absolute number of peripheral blood mononuclear cells, such as leukocytes,
      neutrophils, monocytes, lymphocytes, CD4+, CD8+, CD25+ T cells and CD20+ B cells.
      Monthly blood samples were taken from 26 normal volunteers during one calendar
      year. The estimated inter- and intra-individual C.V. values for plasma Hp were
      27.9% and 20.0%, respectively; the index of individuality was 0.72. No
      significant seasonal rhythms could be detected in plasma Hp levels. The yearly
      mean values in plasma Hp were significantly and positively related to those in
      plasma Fb, absolute number of leukocytes, neutrophils, CD4+ T cells and the
      CD4+/CD8+ T cell ratio. 49.0% of the variance in the yearly mean values of plasma
      Hp could be explained by variances in serum IL-6 and number of CD4+ (positively
      related) and CD8+ (negatively related) T cells. There were significant and
      positive time relationships between plasma Hp, on the one hand, and plasma Fb,
      sIL-6R, sIL-2R and number of leukocytes, neutrophils and monocytes, on the other.
      A smaller part of the within-subject variability in plasma Hp (i.e. 6.0%) could
      be explained by serum sIL-6R and sIL-2R. It is concluded that there are (1)
      important between-subject differences in the homeostatic setpoints of plasma Hp,
      which are related to those in plasma Fb and in immune status and (2) significant
      within-subject, time relationships between plasma Hp and indicators of immune
      activation and plasma Fb.

PMID- 7586585
TI  - A method for the separation of delta bilirubin using Cibacron Blue affinity
      chromatography.
AB  - We developed and evaluated a method for the separation of delta bilirubin (B
      delta) by micro-column affinity chromatography based on Cibacron Blue 3G-A
      Agarose. Untreated serum was applied to affinity columns and free non-protein
      bound bilirubins were eluted with phosphate buffer containing 20 g/l Triton X
      100. Retained albumin was eluted using caffeine-benzoate reagent and bilirubin
      associated with this fraction (B delta) quantitated by the method of Jendrassik
      and Grof modified by Doumas et al (Clin Chem 1985;31:1779-1789); results
      correlated well with the high performance liquid chromatography (HPLC) method (n
      = 35, y (affinity) = 1.009x (HPLC)-5.49; r = 0.959) described by Lauff et al. (J
      Chromatography 1981;226:391-402). Two controls analyzed with each batch gave
      between-batch imprecision less than 4.0% (n = 10; Control 1, mean = 20.05
      mumol/l; Control 2, mean = 74.82 mumol/l). Within-batch imprecision was less than
      3.3% for both levels. Specimens collected from 25 neonates less than 20 days of
      age showed a B delta concentration of 1.7 +/- 0.7 mumol/l (mean +/- 1 S.D.) and
      percent B delta of 2.2 +/- 1.9 (mean total bilirubin +/- 1 S.D. = 118 +/- 79
      mumol/l). Although time consuming, this simple and precise method allows the
      measurement of B delta in laboratories without the need for specialized
      instruments.

PMID- 7586586
TI  - Interaction of human pregnancy-associated plasma protein-A with serine
      proteinases.
AB  - Human pregnancy-associated plasma protein A (PAPP-A) inhibited significantly the
      proteolytic activity of bovine trypsin and human plasmin. Trypsin or plasmin
      treatment of PAPP-A resulted in the generation of a major 85 kDa component and
      the rapid cleavage of internal thiol esters. The results indicated that both of
      these serine proteinases bound in a 1:1 stoichiometry to PAPP-A. The PAPP-A-bound
      enzymes were found to be enzymatically active towards small synthetic substrates
      and inaccessible to inactivation by soybean trypsin inhibitor and alpha 1
      proteinase inhibitor. The mechanism of proteinase inhibition was likely to be
      entrapment, as described for alpha 2-macroglobulin.

PMID- 7586588
TI  - Determination of ammonia in ear-lobe capillary blood is an alternative to
      arterial blood ammonia.
AB  - Blood ammonia determination is a laboratory test to diagnose hepatic
      encephalopathy. Arterial blood is superior to peripheral venous blood ammonia
      because of ammonia metabolism in muscle. We have compared capillary with arterial
      whole blood ammonia as capillary sampling is an attractive alternative. Ear-lobe
      capillary blood ammonia (ECA) was determined in all 173 persons studied,
      fingertip capillary blood ammonia (FCA) in 46 of these and arterial blood ammonia
      (AA) in 113. Of the 173, 60 were healthy (H), 64 were patients, not liver
      diseased (NLD) and 49 had liver disease (LD). Reference values, median and
      ranges, mumol NH3-N/l: AA, NLD, n = 64: 17 (7-42); ECA, H = NLD (P = 0.9), n =
      124: 20 (7-45); FCA, H = NLD (P = 0.8), n = 33: 70 (29-151). Within the NLD group
      (n = 64) AA values (range 7-42) were little but significantly lower than the ECA
      values (range 7-45, P = 0.002). FCA NLD > AA NLD (n = 14, P < 0.0001); FCA H+NLD
      > ECA (n = 33, P < 0.0001). AA correlated very well with ECA, r = 0.87 (n = 113,
      P < 0.0001) and less well with FCA, r = 0.56 (n = 27, P < 0.01). ECA correlated
      with FCA, r = 0.51 (n = 46, P < 0.001). Ear-lobe capillary blood ammonia thus
      accurately reflects arterial ammonia and is an attractive alternative. The higher
      fingertip ammonia may be due to contamination with ammonia-rich sweat from finger
      grooves, regardless of the precautions taken.

PMID- 7586587
TI  - Sensitivity and specificity of a new ELISA method for determination of
      chromogranin A in the diagnosis of pheochromocytoma and neuroblastoma.
AB  - We have evaluated a new commercially available ELISA kit for determination of
      plasma chromogranin A with respect to its usefulness in the diagnosis of
      neuroendocrine tumors, mainly pheochromocytoma. Serum and differently
      anticoagulated plasmas gave different chromogranin A concentrations. Control
      values (n = 21) were 18.9 +/- 5.8 units/l. Chromogranin A values > 30.4 units/l
      (mean + 2 S.D.) were considered elevated. In 22 patients suspected of (but found
      not to have) pheochromocytoma and in 24 patients with renovascular hypertension,
      18% were found to have elevated chromogranin A concentrations. In renovascular
      hypertension chromogranin A correlated positively with serum creatinine;
      chromogranin A was strongly elevated especially in chronic renal failure. In 45
      patients with pheochromocytoma, 13 (29%) had chromogranin A concentrations within
      the normal range, as had 3 out of 11 patients with neuroblastoma (27%). In 13
      pheochromocytoma patients with elevated chromogranin A, measurements were
      repeated after surgical removal of the tumor; values then all fell within the
      normal range. We conclude that measurement of chromogranin A adds little to
      already existing methods for the diagnosis of pheochromocytoma.

PMID- 7586590
TI  - Plasma non-esterified fatty acid response to dialysate acetate concentration
      during haemodialysis in humans.
AB  - We have inhibited the in vitro generation of non-esterified fatty acids in plasma
      samples taken during haemodialysis by cooling the samples rapidly, centrifuging
      and freezing within 5 min of sampling and completing the assay on the same day.
      The relationship of non-esterified fatty acid concentrations during haemodialysis
      to the acetate concentration of the dialysate and the profile of circulating
      lipase activities was studied. With this sample-handling protocol we found lower
      non-esterified fatty acid concentrations than reported in many other studies and
      the results suggest that, under normal conditions of haemodialysis, the
      circulating non-esterified fatty acid concentrations and the associated risk of
      unwanted side-effects may have been previously over-estimated due to artefactual
      in vitro sample lipolysis. We also showed that, at the end of dialysis, when
      circulating lipase activities were least, the non-esterified fatty acid
      concentrations were lower (P < 0.05) with an acetate dialysate containing 37
      mmol/l acetate than with a bicarbonate dialysate containing 3 mmol/l acetate.

PMID- 7586589
TI  - Micronutrient antioxidant status in black South Africans with chronic
      pancreatitis: opportunity for prophylaxis.
AB  - Biochemical assessments of micronutrient antioxidant status were done in 14
      consecutive black patients with calcific chronic pancreatitis and 15 controls at
      Soweto, near Johannesburg in southern Africa. The patients showed subnormal
      levels of vitamin C in plasma; selenium, beta-carotene and alpha-tocopherol in
      serum; and inorganic sulphate (as an index of long-term sulphur amino acid
      intake) in urine (P < 0.001 for each): furthermore, among the patients ascorbate
      constituted a lower fraction of vitamin C (P < 0.002), indicating heightened
      oxidation of the bioactive form. By comparing the results in Sowetan controls
      with reference ranges from Manchester, UK, the markedly lower vitamin C and,
      hence, ascorbate levels in the Sowetans was underlined (P < 0.001) and their
      selenium levels were also lower (P < 0.001), but beta-carotene, alpha-tocopherol
      and inorganic sulphate levels were comparable. The very low bioavailability of
      ascorbate among Sowetan controls is reminiscent of our previous finding in
      outwardly healthy people at Madras in southern India: in both these areas chronic
      pancreatitis is currently endemic, has a propensity to pancreatic calculi and
      runs a virulent course towards premature death from diabetes, malnutrition or
      pancreatic cancer. Considering that low ascorbate levels are a feature in
      patients with chronic pancreatitis who develop pancreatic calculi at Manchester
      and that antioxidant supplements ameliorate painful symptoms, we suggest that
      poor antioxidant intake may predispose underprivileged tropical communities to
      the disease. If so, there could be an opportunity for prophylaxis through a daily
      tablet containing vitamin C, perhaps along with selenium at Soweto and beta
      carotene at Madras.

PMID- 7586591
TI  - Quantitative cytochemistry of human leukocyte elastase compared with plasma
      elastase and acute phase proteins in inflammatory diseases.
AB  - Plasma levels of human leukocyte elastase, a serine proteinase stored in the
      azurophilic granules of polymorphonuclear granulocytes, increase in the early
      stages of several inflammatory diseases. We studied the intracellular enzyme
      activity by cytochemical quantitative image analysis and the amount of elastase
      released in plasma by an automatic immunoactivation immunoassay method in 66
      patients with inflammatory diseases and in a control group. The patients were
      divided into two groups with infective disease (severe and moderate) and one
      group with non-infective inflammation. Intracellular activity and plasmatic
      levels of elastase were also compared with other inflammatory markers, i.e.
      erythrocyte sedimentation rate, C-reactive protein, alpha 1-antitrypsin,
      haptoglobin, alpha 1-acid glycoprotein and fibrinogen. Our studies suggest that
      plasma and leukocyte elastase are correlated both with etiology and with the
      severity of the inflammation.

PMID- 7586592
TI  - The investigation of female infertility.

PMID- 7586593
TI  - Response to methimazole in Graves' disease. The European Multicenter Study Group.
AB  - OBJECTIVE: A variety of regimens continue to be used in the treatment of Graves'
      disease with antithyroid drugs. We have investigated the factors which determine
      the initial response to methimazole (time until euthyroidism is achieved) in
      Graves' disease. PATIENTS: Five hundred and nine patients with Graves' disease in
      different European countries with normal and subnormal iodine supply. Patients
      were randomized to treatment with either 10 or 40 mg of methimazole per day for
      one year, with levothyroxine supplementation as required to maintain
      euthyroidism. Investigations were carried out before treatment and at 3 and 6
      weeks and 3, 6, 9 and 12 months. MEASUREMENTS: Response was assessed by serial
      measurements of serum thyroid hormones. TSH receptor antibodies, thyroid
      autoantibodies and urinary iodide excretion were measured centrally. Twenty
      minute thyroid uptake was measured by standard techniques. Data were collected
      and analysed centrally. Standard techniques as well as a stepwise logistic
      regression model were used to examine the relations between methimazole dose,
      age, goitre size, presence of endocrine eye signs, thyroid hormone levels,
      urinary iodide excretion, thyroid uptake, index of disease severity (Crooks),
      presence of TSH receptor antibodies and duration of the hyperthyroid phase.
      RESULTS: Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and
      77.5% responded within 6 weeks. The corresponding figures for 40 mg of
      methimazole were 64.6 and 92.6%. Significant associations were found between
      duration of hyperthyroidism and the following variables: goitre size, urinary
      iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb),
      index of disease severity (Crooks) and pretreatment thyroid hormone levels.
      Response to methimazole was delayed in patients with large goitres, iodine
      excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid
      hormone levels, elevated levels of TBIAb and treatment with only 10 mg of
      methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks
      when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide
      was above 100 micrograms/g. By stepwise logistic regression, the main factors for
      the response to methimazole were daily dose, pretreatment T3 levels, and goitre
      size. CONCLUSION: Methimazole dose, pretreatment serum T3 levels, and goitre size
      are the main determinants of the therapeutic response to methimazole in Graves'
      disease, at least in areas comprising low, subnormal and normal iodine supply.

PMID- 7586594
TI  - Altered endogenous growth hormone secretory kinetics and diurnal GH-binding
      protein profiles in adults with chronic liver disease.
AB  - OBJECTIVE: Increased serum GH concentrations and GH responses to a variety of
      stimuli have been reported in patients with chronic liver disease (CLD). We
      investigated the pulsatile pattern of endogenous GH release and GH-binding
      protein (GHBP) and insulin-like growth factor-I (IGF-I) diurnal profiles in
      adults with cirrhosis, in comparison with healthy, matched control subjects.
      DESIGN: Case-control, cross-sectional. PATIENTS: Seven patients with biopsy
      proven cirrhosis, and sex, age, height, weight and oestrogen status matched
      controls. MEASUREMENTS: Serum immunoreactive GH concentrations in samples
      collected at 20-minute intervals for 24 hours were analysed using a multi
      parameter deconvolution method to simultaneously resolve endogenous GH secretory
      and disappearance rates. Diurnal patterns of GHBP (specific immunoprecipitation
      method) and serum IGF-I (RIA after acid-ethanol extraction) were assessed.
      RESULTS: The mean daily GH secretion rate in patients with CLD was increased (210
      +/- 93 vs 100 +/- 55 mU/I/day; P = 0.025), and GH disappearance half-time was
      prolonged (43 +/- 10 vs 24 +/- 9 min; P = 0.006) compared to controls. Detectable
      GH secretory bursts were more frequent in patients with CLD (10 +/- 1 vs 6 +/-
      3/day; P = 0.038), but of similar mean mass (21 +/- 10 vs 17 +/- 8 mU/I) compared
      to controls. In patients with CLD, mean serum GHBP was slightly lower (63 +/- 36
      vs 71 +/- 14% pooled control; P > 0.1). Fasting serum IGF-I concentrations (after
      size-exclusion HPLC) were lower in the patients with CLD (13 +/- 5 vs 21 +/- 2
      nmol/l; P < 0.0001). Multiple regression analysis showed that GH secretion rate
      was increased in patients with CLD with higher Child's classifications (R2 =
      0.86; P = 0.002) and with lower serum IGF-I concentrations measured after HPLC
      (R2 = 0.11; P = 0.044). CONCLUSIONS: Adults with chronic liver disease have (1)
      increased total daily GH secretion rates, which appear to be influenced by
      disease severity and diminished serum IGF-I-mediated negative feedback; (2)
      markedly impaired endogenous GH clearance, possibly reflecting changes in hepatic
      GH-receptor status; and (3) GHBP levels which do not correlate with GH kinetics
      or serum IGF-I concentrations.

PMID- 7586595
TI  - Thirst induced by a suckling episode during breast feeding and relation with
      plasma vasopressin, oxytocin and osmoregulation.
AB  - OBJECTIVE: There have been anecdotal reports of increased maternal thirst during
      breast feeding, but the physiological mechanisms remain obscure. We have assessed
      and quantified the stimulation of maternal thirst during breast feeding
      (suckling), and correlated the changes with plasma oxytocin and vasopressin
      levels. DESIGN: A within subject design was used with each subject acting as her
      own control. Each subject participated in a suckling period and a control non
      suckling period the order of which was counterbalanced. SUBJECTS: Ten healthy
      breastfeeding women ranging from 28 to 52 days post partum. MEASUREMENTS: Thirst
      (assessed by a visual analogue scale), plasma vasopressin, plasma oxytocin (pOT),
      plasma osmolality and haematocrit, blood pressure, volume of milk transferred to
      baby, volume of water drunk immediately following each experimental period.
      RESULTS: Thirst increased significantly more over a suckling period than over a
      comparable control period (P = 0.013). The peak level of thirst correlated with
      the volume of water consumed to satiety following the suckling period (r = 0.7, P
      = 0.024). As expected, pOT levels rose significantly in response to suckling (P <
      0.001). Six women demonstrated a close relation between thirst and oxytocin
      response during the suckling period. Despite significant changes in thirst during
      suckling there was no increase in plasma vasopressin or in osmoregulatory
      parameters. CONCLUSIONS: This study confirms that suckling is a potent stimulus
      to thirst in the mother, and is not associated with vasopressin release or
      dependent on any measurable alterations in osmoregulation. What actually
      stimulates thirst during breast feeding remains unknown, but there are two
      potential explanations for these observations: (1) suckling sends nerve impulses
      to the paraventricular and supraoptic nuclei in the hypothalamus which may have
      afferents within the central nervous system which stimulates a thirst response
      simultaneous with oxytocin release; (ii) a learned anticipation of thirst may be
      occurring in a situation associated with expectant fluid loss to preserve
      homeostasis.

PMID- 7586597
TI  - Menstrual disturbance and hypersecretion of progesterone in women with congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - OBJECTIVE: While menstrual disturbance is often quoted as a feature of congenital
      adrenal hyperplasia (CAH), little is known about the mechanism of this symptom.
      We set out to determine the relationship between menstrual pattern and
      biochemical characteristics of women with CAH due to 21-hydroxylase deficiency.
      PATIENTS AND DESIGN: All 21 female patients with classic CAH attending the adult
      endocrinology clinics at The Middlesex Hospital were reviewed. Their ages at
      menarche and menstrual pattern were recorded and blood samples were taken in the
      follicular phase of the menstrual cycle when on their usual maintenance therapy.
      MEASUREMENTS: Measurements of serum LH, FSH, progesterone, 17 alpha
      hydroxyprogesterone, testosterone, androstenedione and plasma renin activity were
      recorded. Urinary steroid profiles were obtained by gas chromatography and mass
      spectrometry. Molecular genetic analysis of the 21-hydroxylase gene was performed
      on leucocyte DNA. RESULTS: In the 18 patients who had spontaneous menarche the
      degree of menstrual disturbance and progesterone excess was related to the
      effectiveness of adrenal suppressive therapy. Three out of 21 patients, however,
      failed to experience menarche on standard medical therapy. These patients with
      primary amenorrhoea were characterized by reduced endometrial thickening, by non
      suppressible serum progesterone concentrations despite suppression of 17 alpha
      hydroxyprogesterone levels and by the presence of progesterone metabolites in
      urinary steroid profiles. Molecular genetic analysis did not differentiate
      between patients with raised progesterone concentrations and those without.
      CONCLUSION: A subgroup of women with congenital adrenal hyperplasia have the
      triad of non-suppressible serum progesterone of adrenal origin, primary
      amenorrhoea and infertility due to failure of endometrial thickening. The
      characteristic urinary steroid profile best distinguishes this subgroup of women
      from others with congenital adrenal hyperplasia and menstrual disturbance due to
      inadequate adrenal suppression.

PMID- 7586596
TI  - The effects of alcoholism on the hypothalamic-pituitary-adrenal axis: interaction
      with endogenous opioid peptides.
AB  - BACKGROUND: Abnormal baseline hypothalamic-pituitary-adrenal axis function and
      dexamethasone suppressibility seen in withdrawing alcoholics returns to normal on
      abstinence, but some studies report blunting of the ACTH response to CRH
      persisting during the early abstinence phase. Reduced central levels of
      endogenous opioid peptides have been postulated to have an aetiological role in
      alcohol addiction. AIMS: To evaluate hypothalamic-pituitary-adrenal axis function
      in a group of recently abstinent alcoholics using basal hormone data, naloxone
      (an opioid receptor antagonist), and ovine CRH. SUBJECTS: Nine alcoholics (age
      41.4 +/- 3.1 years) studied more than one week after the acute withdrawal period
      but within 6 weeks of cessation of drinking, and nine age and sex matched non
      alcoholic controls. PROTOCOL: Cortisol, ACTH, CRH and AVP levels were measured
      every 20 minutes for 2 hours between 0900 and 1100h Twenty mg naloxone i.v. was
      administered at 1100h (0 minutes) and further samples for the above hormones were
      taken at 15, 30, 45, 60, 90 and 120 minutes. On a separate occasion, again at
      1100h, oCRH 1 microgram/kg (n = 7 alcoholics, n = 6 controls) was administered,
      with samples for cortisol, ACTH and AVP taken at the same times. STATISTICS:
      Results were examined by analysis of variance for repeated measures (ANOVA),
      while incremental hormone response and area under the secretory curve (AUC) in
      alcoholics versus controls were compared by the two-tailed Student's t-test.
      Linear regression analysis was carried out to examine the relation between basal
      cortisol and hormone responses to naloxone and oCRH. RESULTS: Basal hormone
      levels did not differ between the groups. The alcoholics had a blunted ACTH
      incremental response to naloxone (11.4 +/- 3.0 vs 21.1 +/- 2.5 pmol/l, P < 0.05)
      but the cortisol response was not significantly different (205 +/- 51 vs 305 +/-
      42 nmol/l, P = 0.15). The alcoholics also had a blunted ACTH incremental response
      to oCRH (28.7 +/- 4.2 vs 41.2 +/- 3.7 pmol/l, P = 0.052) and by ANOVA a
      significant main effect of group (alcoholic vs control) was seen (P < 0.02) for
      the ACTH response to oCRH. There was no difference between the groups in the
      cortisol incremental response to oCRH. In the control subjects, a negative
      correlation was found between basal cortisol and the cortisol increment (r = 
      0.82, P < 0.05) and ACTH increment (r = -0.81, P = 0.052) following oCRH, while
      in contrast, basal cortisol correlated positively with cortisol increment (r =
      0.72, P < 0.05) following naloxone. There was also a trend for basal cortisol to
      correlate positively with ACTH increment following naloxone in the controls (r =
      0.63, P < 0.07). In the alcoholics, the normal negative effect of basal cortisol
      on the cortisol increment after oCRH was reversed, with a positive correlation
      between basal cortisol and cortisol increment (r = 0.75, P = 0.05). CONCLUSIONS:
      Recently abstinent alcoholics with normal basal HPA axis hormone levels have a
      blunted ACTH response to naloxone and oCRH. While reduced levels of central
      endogenous opioid peptides may be a factor in the blunted ACTH response to
      naloxone in the alcoholics, it is proposed that the alcoholics have reduced
      pituitary responsiveness to CRH. This may be via a direct pituitary effect of the
      chronic ethanol exposure or by a reduction in hypothalamic-hypophyseal
      vasopressin levels.

PMID- 7586599
TI  - Raised serum 11-deoxycortisol in men with persistent acne vulgaris.
AB  - OBJECTIVE: Acne vulgaris is androgen dependent but the hormonal mechanisms are
      unclear. Although there have been many studies of serum hormones in women with
      acne there are few studies in men and the results are conflicting. We have
      therefore carried out a further study in men. DESIGN AND PATIENTS: Fifty men with
      acne vulgaris were age-matched against 50 normal men. MEASUREMENTS: Serum levels
      of dehydroepiandrosterone sulphate (DHEAS), 17 alpha-hydroxyprogesterone, 11
      deoxycortisol, androstenedione and testosterone were measured by
      radioimmunoassay, sex hormone binding globulin (SHBG) by immunoradiometric assay
      and LH, FSH and oestradiol by automated ELISA. RESULTS: The acne patients had
      higher levels of androstenedione, median 7.35 nmol/l, (interquartile range 2-7)
      vs 6.05 (2.3), P = 0.004; testosterone, 21.7 nmol/l (7.5) vs 17.55 (7.7), P =
      0.04; and free androgen index (FAI) 78.26 (40) vs 65.06 (20), P = 0.007, but also
      had higher levels of 11-deoxycortisol, 13.65 nmol/l (4.3) vs 12.0 (4.3), P =
      0.022. The LH, FSH, 17 alpha-hydroxyprogesterone, DHEAS, oestradiol and SHBG
      levels were not significantly different. Examination of the Spearman rank
      correlation coefficient matrices for the serum levels of 17 alpha
      hydroxyprogesterone, androstenedione and 11-deoxycortisol showed that the
      strongest correlation was between androstenedione and 11-deoxycortisol.
      CONCLUSION: Although there was overlap between the results of the acne patients
      and controls the acne patients tended to have higher levels of androstenedione,
      testosterone, free androgen index and 11-deoxycortisol. The higher levels of 11
      deoxycortisol are suggestive of 11 beta-hydroyxlase dysfunction which could be
      due to a primary adrenal defect or a consequence of raised androgens. Also, a
      pathway between androstenedione and 11-deoxycortisol has been described in sheep
      and, although unsubstantiated in man, requires consideration.

PMID- 7586598
TI  - Prevalence of an immunological LH beta-subunit variant in a UK population of
      healthy women and women with polycystic ovary syndrome.
AB  - OBJECTIVE: An immunological LH beta-subunit variant has been described, which is
      undetectable using monoclonal antibodies directed to the intact LH molecule
      alone. Subjects have been found homozygous or heterozygous for nucleotide
      mutations within codons 8 and 15 in the LH beta-subunit gene. The prevalence of
      the variant LH beta-subunit has been estimated in a healthy UK population of
      women of reproductive age and in women with polycystic ovary syndrome (PCOS). The
      relationship of the variant molecule to the clinical and hormonal parameters of
      the subjects has been evaluated. DESIGN: The control and PCOS subjects were
      screened for the presence of the mutation by using a ratio of two
      immunofluorometric assays using monoclonal antibodies (Mab). One assay, not
      detecting the LH variant, uses a Mab directed to the intact LH molecule and a
      beta-specific Mab. The other assay, detecting both the variant and wild-type LH,
      uses two beta-subunit specific Mabs. The mutations in the LH beta-subunit gene
      were confirmed by restriction fragment length polymorphism. The relationship of
      the presence of the variant to the clinical and hormonal parameters was assessed
      by ANOVA. PATIENTS: Two hundred and twelve normal ovulatory women, of whom 66
      (31%) were obese (body mass index > 25) and 146 (69%) non-obese, and 153 women
      with PCOS, 115 (75%) obese and 38 (25%) non-obese participated in the study.
      RESULTS: The variant LH was detected in 31 (15%) controls and 32 (21%) PCOS
      subjects (P = 0.124) using specific Mab. Obese PCOS had a higher incidence of the
      heterozygous LH variant compared to obese controls (odds ratio 2.5, P = 0.03),
      and compared to non-obese PCOS (odds ratio 6.3, P = 0.01). The previously
      described two mutations in codon 8 and codon 15 were present in all subjects
      detected to be mutant hetero of homo-zygous by RFLP. There was no relationship
      between the presence of the variant LH and the clinical and hormonal parameter in
      the PCOS subjects; however, in the controls the presence of the variant LH was
      associated with a higher serum total testosterone (P = 0.046), oestradiol (P =
      0.03) and SHBG (P = 0.002). CONCLUSIONS: The results of this study show that the
      variant LH beta-subunit is a common polymorphism occurring in 15% of a healthy UK
      population of women. The prevalence was not higher in women with PCOS, though it
      was over represented in obese women with PCOS. The presence of the variant did
      not alter the clinical or hormonal expression of the disorder in women with PCOS.
      Its presence in the controls was however associated with higher serum oestradiol
      and probably secondary elevation of SHBG and testosterone, suggesting that the
      variant form of LH may be associated with subtle changes in the function of the
      hypothalamic-pituitary-gonadal axis.

PMID- 7586600
TI  - Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects.
AB  - OBJECTIVE: The standard ACTH test in clinical use employs a pharmacological dose
      of ACTH which assesses the maximum secretory capacity of the adrenal cortex. We
      have investigated the responses of plasma adrenocortical steroids including
      cortisol, aldosterone and dehydroepiandrosterone (DHEA) to physiological doses of
      ACTH (ACTH 1-24, tetracosactide, Cortrosyn) and determined the minimal dose which
      induces a response equivalent to that induced by a pharmacological dose of ACTH.
      DESIGN: Rapid ACTH tests at various physiological (0-1, 0.5, 1 and 5 micrograms)
      and standard pharmacological (250 micrograms) intravenous doses. SUBJECTS: Seven
      healthy normal volunteers. MEASUREMENTS: Plasma cortisol, aldosterone and DHEA
      were measured. Peak value and the increment from basal value were used as indices
      of responses. RESULTS: Each steroid responded to physiological doses of ACTH in a
      dose dependent manner. The minimum dose inducing an equivalent response to 250
      micrograms ACTH was 0.5 micrograms for peak and incremental values in cortisol
      and DHEA, while that for aldosterone was 0.1 microgram. The time to peak for each
      steroid was delayed as the dose increased. Plasma aldosterone and DHEA peaked
      significantly earlier than plasma cortisol in 1-5 micrograms and 0.5-5-micrograms
      ACTH tests, respectively. CONCLUSIONS: These results suggest that the sensitivity
      of secretion to physiological doses of ACTH in descending order is aldosterone >
      DHEA = cortisol. When peak and incremental values are used, sufficient doses of
      ACTH are 0.1 microgram for plasma aldosterone and 0.5 microgram for plasma
      cortisol and DHEA in the rapid ACTH test.

PMID- 7586601
TI  - Combined treatment of growth hormone and the bisphosphonate pamidronate, versus
      treatment with GH alone, in GH-deficient adults: the effects on renal phosphate
      handling, bone turnover and bone mineral mass.
AB  - OBJECTIVE: A potential drawback of GH replacement therapy in GH deficient (GHD)
      patients is the initial decrease in bone mass. The present study investigates the
      effects of the addition of pamidronate to GH replacement therapy in adult GHD
      subjects, on serum PTH and 1,25-dihydroxyvitamin D3 (1.25-(OH)2D3) levels, renal
      phosphate handling, bone turnover and bone mineral content (BMC). DESIGN: Six GHD
      adult patients were studied for two periods of 6 months with a wash-out period of
      3 years. In the first period they were treated with conventional replacement
      therapy and GH. In the second study period GH treatment was identical, while
      after 2 weeks 150 mg pamidronate per day was added. RESULTS: In the first study
      period (GH only) there was a significant increase of phosphate reabsorption,
      without a change in serum PTH and 1.25-(OH)2D3 levels. This suggests a specific
      effect of GH or IGF-I on renal phosphate handling. This was supported by the
      close correlation between serum IGF-I levels and TmP/GFR (r = 0.75, P < 0.0001).
      When GH was administered together with pamidronate, this correlation was less,
      but remained significant (r = 0.44, P < 0.001). The increase in bone turnover and
      decrease in BMC, as initially observed during GH replacement therapy alone, were
      attenuated by simultaneous pamidronate administration. The decline in lumbar
      spine BMC (measured with dual-photon absorptiometry) at 6 months was -3.1 +/-
      1.5% during GH replacement therapy alone vs an increase of +3.8 +/- 2.0% during
      the administration of the combination of GH and pamidronate (measured with dual
      energy X-ray absorptiometry). At the distal and proximal forearm the changes
      amounted to -0.5 +/- 3.4% vs +4.5 +/- 1.8% and -1 +/- 1.2% vs +1.2 +/- 1.1%
      respectively. CONCLUSIONS: This study shows that the addition of a bisphosphonate
      to GH replacement therapy in GHD adults counteracts the GH (or IGF-I) induced
      increase in renal phosphate reabsorption. Furthermore, it reduces GH induced bone
      turnover and prevents the initial decrease in bone mineral content seen during GH
      treatment alone, resulting in a beneficial effect on bone mineral mass.
      Pamidronate might therefore be an important adjunct to GH replacement therapy in
      adults with GHD and severe osteopenia during the early phase of GH induced
      stimulation of bone turnover.

PMID- 7586602
TI  - Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?
AB  - OBJECTIVE: The persistent controversy as to the best approach to radioiodine dose
      selection in the treatment of hyperthyroidism led us to perform a study in order
      to compare a fixed dose regime comprising doses of 185 370 or 555 MBq based on
      gland size assessment by palpation only, with a calculated 131I dose based on
      type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate
      thyroid volume measurement, and a 24-hour 131I uptake determination. DESIGN:
      Prospective randomized study. PATIENTS: Two hundred and twenty-one consecutive
      hyperthyroid patients referred for 131I treatment. Four Patients who died for
      reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not
      receive antithyroid drugs after treatment, were excluded. The remaining 163
      patients (143 women) were studied, divided into subgroups according to the type
      of gland. They all received antithyroid drugs prior to 131I treatment and this
      was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS: Thyroid
      function variables were determined approximately 2 weeks before 131I treatment,
      and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to 131I therapy the
      size of the thyroid gland was determined by ultrasound and a 24-hour uptake of
      131I was carried out. Thyroid volume was also estimated 12 months after 131I
      therapy in 78 of the 163 patients. Twelve months after the initial 131I dose
      patients could be classified as euthyroid, hyperthyroid or hypothyroid. RESULTS:
      Neither in the group of 163 patients nor within the three subgroups of
      hyperthyroidism could any significant difference in outcome between the two
      treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the
      calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were
      classified as hyperthyroid. Seven of 78 (9%) in the calculated dose group and 6
      out of 85 (7%, NS) in the fixed dose group were classified as permanently
      hypothyroid. Finally, 39 of 78 (50%) in the calculated dose group and 49 of 85
      (58%, NS) in the fixed group were euthyroid at 12 months after 131I treatment.
      One year after 131I therapy thyroid volume was reduced from 59.3 +/- 9.2 (mean +/
      SEM) to 36.2 +/- 6.6 ml (average reduction 39%) in the calculated dose group (P
      < 0.001). This reduction did not differ significantly from the fixed dose group
      where thyroid volume declined from 61.6 +/- 6.1 to 41.17 +/- 4.7 ml (average
      reduction 32%) (P < 0.001). CONCLUSIONS: A semiquantitative approach is probably
      as good as the more elaborately calculated radioiodine dose for treatment of
      hyperthyroidism. It is clearly more cost effective and allows the use of
      predetermined standard doses.

PMID- 7586603
TI  - Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver
      disease before and after liver transplantation.
AB  - OBJECTIVE: Gonadal dysfunction is common in chronic liver disease, but most of
      the previous studies have been restricted to men with alcohol-induced liver
      disease. We have evaluated hypothalamic-pituitary-testicular function in patients
      with end-stage non-alcoholic liver disease before and at 6 and 12 months after
      hepatic transplantation. DESIGN: A prospective study of hypothalamic-pituitary
      testicular endocrine function before and after cadaveric hepatic transplantation.
      PATIENTS: Fifty four consecutive patients with end-stage, non-alcoholic liver
      disease were evaluated before and after liver transplantation. MEASUREMENTS:
      Hypothalamic-pituitary-testicular (HPT) axis function was evaluated under basal
      conditions by single morning measurements of plasma total and free testosterone,
      sex hormone-binding globulin and by plasma LH and FSH responses to 100 micrograms
      i.v. GnRH. RESULTS: Men with chronic non-alcoholic liver disease had reduced
      levels of total and free testosterone and increased levels of SHBG compared with
      controls with normal liver function. Total and free testosterone were positively
      correlated with basal and stimulated LH (but not FSH) concentrations.
      Gonadotrophin responses to GnRH were preserved but delayed compared with healthy
      controls consistent with a predominantly hypothalamic defect in regulation of
      pituitary-testicular function. Increasing severity of underlying liver disease
      was associated with declining total and free testosterone as well as peak GnRH
      stimulated LH concentrations. Spironolactone treatment was associated with
      decreased circulating testosterone levels only in men with liver disease of
      intermediate severity (Child-Pugh class B). Following hepatic transplantation,
      total and free testosterone and SHBG concentrations returned progressively
      towards eugonadal control levels over the first 12 months but total and free
      testosterone levels remained subnormal. CONCLUSIONS: Hypothalamic-pituitary
      regulation of testicular function is impaired in end-stage non-alcoholic liver
      disease in proportion to the severity of underlying liver disease. Spironolactone
      reduces circulating testosterone but only among men with Child-Pugh B liver
      cirrhosis. Gonadal function improves, but is not normalized, over the first year
      following successful liver transplantation.

PMID- 7586606
TI  - Vitamin D status in primary hyperparathyroidism in India.
AB  - OBJECTIVES: Primary hyperparathyroidism is a syndrome with variable clinical
      expression, presenting as asymptomatic hypercalcaemia in Western countries and
      with predominant bone disease in developing countries. Vitamin D deficiency has
      been implicated as the cause of bone disease. There is a paucity of information
      on the vitamin D (25-OHD3) status of patients with primary hyperparathyroidism
      presenting with bone disease. The present study aims to evaluate the vitamin D
      status in patients with primary hyperparathyroidism and to correlate it with the
      bone disease. DESIGN: Twenty consecutive patients with primary
      hyperparathyroidism admitted to the endocrinology and metabolism wards of the All
      India Institute of Medical Sciences were analysed to assess their clinical,
      radiological and biochemical features, as well as parathyroid hormone (mid
      molecular, PTH-MM) and 25-OHD3 levels. MEASUREMENTS: PTH-MM levels and 25-OHD3
      levels were measured using RIA kits. RESULTS: Bone disease (osteitis fibrosa
      cystica) was the mode of presentation in 90%. Radiologically, sub-periosteal
      resorption was present in 90% of the total group of patients, brown tumours in
      60%, and pathological fractures in 40%. Renal stones and/or nephrocalcinosis was
      present in 50% of patients. Mean serum calcium, phosphate and alkaline
      phosphatase concentrations (mean of 3 days values) were 2.72 +/- 0.24 mmol/l;
      1.01 +/- 0.28 mmol/l and 425 +/- 249 IU/l respectively. The 24-hour (mean of 3
      days values) urine calcium and phosphate excretions were 8.0 +/- 4.2 mmol and
      19.0 +/- 13 mmol. Only 50% of the patients had hypercalcaemia ( > 2.7 mmol/l).
      However, 90% of the whole group of patients had hypercalciuria. The mean serum
      creatinine concentration of patients with hypercalcaemia was 108 +/- 38 mumol/l
      and of those with normocalcaemia 89 +/- 33 mumol/l. The mean serum PTH-MM was 438
      +/- 350 pmol/l (the detection limit for the kit was 34 pmol/l). Ultrasound
      examination detected adenomas in 72% of the cases and computerized tomography of
      the neck localized adenomas in 71% of the cases. The median weight of the adenoma
      was 4.6 g (range 0.125-25 g). Two patients had coexistent hyperplasia of the
      other parathyroid glands and two had recurrent adenomas. 25-OHD3 levels were
      assessed in all 20 patients under fasting conditions. The mean value of 25-OHD3
      observed (8.4 +/- 5.1 micrograms/l) was comparable to the mean value measured in
      14 healthy age and sex matched controls (8.3 +/- 2.5 micrograms/l). CONCLUSION:
      Patients with primary hyperparathyroidism in India presented with bone and renal
      diseases; half were normocalcaemic. All the patients had hypercalciuria despite
      the bone disease. The PTH-MM levels were increased and 25-OHD3 levels were low.
      The predominant bone disease is probably due to prolonged primary
      hyperparathyroidism coexisting with low calcium intake and/or 25-OHD3 deficiency.
      The mean weight of the adenoma was higher than that reported for patients in the
      Western literature.

PMID- 7586604
TI  - Is previous hyperthyroidism still a risk factor for osteoporosis in post
      menopausal women?
AB  - OBJECTIVE: Hyperthyroidism is a risk factor for osteoporosis, but the relative
      contributions of the episode of hyperthyroidism and thyroxine replacement for
      subsequent hyperthyroidism remain uncertain. In this study we have measured bone
      mineral density (BMD) in post-menopausal women with a previous history of
      hyperthyroidism, comparing those requiring thyroxine therapy with those remaining
      euthyroid and with an historical local control population. DESIGN: Cross
      sectional study. PATIENTS: One hundred and six post-menopausal women with a
      previous history of hyperthyroidism. These were divided into four groups: treated
      with radioiodine, remaining euthyroid (group RU, n = 15); treated with
      radioiodine, receiving thyroxine for at least 5 years (group RT, n = 46); treated
      with surgery, remaining euthyroid (group SU, n = 21); treated with surgery,
      receiving thyroxine for at least 5 years (group ST, n = 24). There were 102
      control subjects. MEASUREMENT: Forearm bone mineral density at distal and
      ultradistal sites as measured by single-photon absorptiometry. RESULTS: Results
      were expressed as 'Z-scores' i.e. number of standard deviations from the mean of
      a 5-year age-band from the local control population. Mean Z-scores at distal and
      ultradistal sites were as follows: -0.61 and -0.81 in group RU; -0.58 and -0.56
      in group RT; -0.27 and -0.30 in group SU; -0.81 and -0.57 in group ST. Patients
      in groups RU, RT and ST but not SU had significantly lower BMD than controls.
      CONCLUSION: Post-menopausal women with previous hyperthyroidism treated with
      radioiodine have reduced BMD, whether or not receiving thyroxine. They should be
      targeted for densitometry and protective therapy with oestrogen should be
      considered. Those treated with surgery appear to be at less risk; this may be
      because most are diagnosed and treated whilst premenopausal. Thyroxine may have a
      deleterious effect in this group; longitudinal studies would provide further
      clarification.

PMID- 7586605
TI  - GH responses to intravenous bolus infusions of GH releasing hormone and GH
      releasing peptide 2 separately and in combination in adult volunteers.
AB  - OBJECTIVE: Synthetic growth hormone releasing peptides (GHRP) have potent GH
      releasing activity in vivo and in vitro. The nature of the interaction of GHRP
      and naturally occurring GH releasing hormone (GHRH) is still far from clear. We
      investigated GH release in response to individual peptide doses or combined doses
      of GHRH1-29NH2 and GHRP-2, a novel GH-releasing peptide, in normal adults.
      DESIGN: Subjects underwent three tests in a randomized order: (1) i.v. bolus of
      GHRH1-29NH2 (1 microgram/kg BW), (2) i.v. bolus of GHRP-2 (1 microgram/kg BW),
      (3) i.v. bolus of GHRH1-29NH2 combined with GHRP-2 (same dosages). SUBJECTS:
      Eight healthy non-obese male volunteers, aged 25-34 years. MEASUREMENTS: Serum GH
      concentrations were measured by IRMA at -15, 0, +10, 20, 30, 45, 60, 75, 90 and
      120 minutes after the boluses. RESULTS: Peak GH levels in response to GHRH1
      29NH2, GHRP-2 and the combined GHRH1-29NH2 and GHRP-2 administrations were
      observed between 20 and 45 minutes. Peak GH levels at 30 minutes were 32.8 +/-
      27.3 (mean +/- SD), 109.7 +/- 56.1 and 140.9 +/- 80.6 mU/l, respectively. The
      area under the curve for GH levels (GH AUC) calculated for the first 90 minutes
      after the GHRH1-29NH2 test (2061.2 +/- 1601.9 mU/lmin) was significantly lower
      than those after GHRP-2 (6205.1 +/- 3216.9 mU/lmin) and the combined GHRH1-29NH2
      and GHRP-2 challenge (9788.3 +/- 5530.4 mU/lmin) (P = 0.0003 and P = 0.00005,
      respectively; paired Student's t-test for log transformed data). Although the GH
      AUC of the GHRP-2 test and the combined GHRH1-29NH2 and GHRP-2 test differed
      significantly (P = 0.016, t-test), the latter was not significantly different
      from the sum of the GH AUCs of each subject after the separate tests. CONCLUSION:
      Although the GH releasing potency of GHRP-2 significantly exceeded that of GHRH1
      29NH2, we were not able to demonstrate synergy between the two substances. It is
      possible that GHRP-2 given in our study GHRP-2 significantly exceeded that of
      GHRH1-29NH2, we were not able to demonstrate synergy between the two substances.
      It is possible that GHRP-2 given in our study in higher molar quantities than
      GHRH1-29NH2 masked the effect of the latter.

PMID- 7586607
TI  - High prevalence of nodular thyroid disease in patients with Cushing's disease.
AB  - OBJECTIVES: In the recent past, we have noted a frequent occurrence of thyroid
      nodules in our patients with Cushing's disease. We therefore elected to evaluate
      thyroid structure and function in these patients and also in patients with
      Cushing's syndrome of primary adrenal origin. PATIENTS AND METHODS: In 33 of the
      37 patients (30 women and 3 men aged 19-66 years) with endogenous
      hypercortisolism referred to our Institution during the last five years,
      measurement of T4, T3, FT4, FT3, TSH serum levels and thyroid ultrasonography
      were performed, at first admission in 15 cases and subsequently in the course of
      follow-up in 18 cases. At the time of the study, 16 of the 33 patients had active
      Cushing's disease while 9 were in remission after successful surgery, 6 patients
      had an adrenal tumour and 2 patients had previously undergone unilateral
      adrenalectomy for an adrenal adenoma. Thyroid function and ultrasonography were
      also evaluated in 55 normal subjects, 40 women and 15 men aged 20-73 years.
      RESULTS: In 25 patients with Cushing's disease, we found a significantly higher
      prevalence of thyroid nodular disease than that recorded in 55 control subjects
      (60.0 vs 20.0%, chi 2 = 10.779, P < 0.005) and comparable to that in patients
      with active disease (56.2%) and those in remission (66.6%). Multiple nodules were
      present in 8 Cushing's patients and in 4 normal subjects while a single nodule
      was detected in 7 patients and in 7 controls. A markedly lower occurrence of
      thyroid abnormality was found in the 8 patients with adrenal tumours (25.0%, NS
      vs controls). In 9/17 (52.9%) patients with ultrasonographic evidence of thyroid
      nodules, these were palpable. As expected, serum thyroid hormone and TSH levels
      were reduced in patients with active Cushing's syndrome compared to normal
      controls. CONCLUSIONS: We found a significantly higher prevalence of nodular
      thyroid disease in patients with Cushing's disease with respect to a group of
      controls in whom the prevalence of thyroid nodules was comparable to that
      reported for the general population in Europe. The possibility that
      glucocorticoid excess is responsible for the development of thyroid changes does
      not seem likely since in our small series of patients with adrenal tumours the
      prevalence was only slightly higher than that observed in control subjects. Other
      factors related to hyperactivity of the corticotrophic cell, or a growth factor
      stimulating both corticotroph and thyrocyte proliferation might be involved.
      Evaluation of a larger series of patients with adrenal tumours may help to
      distinguish between these possibilities.

PMID- 7586608
TI  - The effect of an opiate antagonist on the hormonal changes induced by hexarelin.
AB  - OBJECTIVE: Growth hormone-releasing peptides (GHRPs) stimulate growth hormone
      (GH) release in vitro and in vivo in animals and in humans. GHRPs were developed
      by modification of the structure of met-enkephalin but GHRP-6 does not activate
      opiod receptors in animal studies. These agents may well have diagnostic and/or
      long-term therapeutic potential in the future so their effects on opiod receptors
      need to be clarified in humans as well. Hexarelin is a recently developed six
      amino acid residue GHRP. DESIGN: We have investigated the effects of 100
      micrograms/kg i.v. dose of the opiate antagonist naloxone and 2 micrograms/kg
      i.v. hexarelin or placebo on serum GH, prolactin, TSH, cortisol and plasma ACTH
      in 12 healthy volunteers in a double-blind, randomized trial. RESULTS: Hexarelin
      significantly stimulated the peak serum levels and area under the curve for
      circulating GH and this effect was not modulated by naloxone. Hexarelin also
      caused significant elevation of circulating prolactin, cortisol and ACTH but did
      not influence circulating TSH levels. The effect of naloxone on cortisol and ACTH
      was stimulatory, while it did not influence prolactin, GH and TSH levels. The
      effect of the two drugs together on cortisol and ACTH was less than additive.
      CONCLUSIONS: This study confirms that the activation of opiate receptors does not
      play a role in the GH-releasing effect of growth hormone-releasing peptides in
      humans.

PMID- 7586609
TI  - Transient osteoporosis of the hip in pregnancy: natural history of changes in
      bone mineral density.
AB  - A 31-year-old white female developed severe bilateral hip pain during the third
      trimester of pregnancy that persisted after parturition. Laboratory abnormalities
      (elevated alkaline phosphatase and erythrocyte sedimentation rate) and
      radiographic changes (faint demineralization of the femur in the more symptomatic
      hip on plain films with evidence of bone marrow oedema and small joint effusions
      bilaterally on MRI) in the absence of other causes of focal osteoporosis were
      consistent with the diagnosis of transient osteoporosis of the hip in pregnancy.
      Although loss of bone mineral density (BMD) characterizes this syndrome, serial
      BMD measurements in symptomatic transient osteoporosis of the hip in pregnancy
      have not previously been reported. In the case reported here, serial bone density
      measurements were obtained over a 4-year period following the onset of symptoms.
      BMD in both femoral necks, which initially was approximately 20% lower than the
      average for age matched controls, increased markedly during the first year,
      plateaued during the following year, and then rapidly increased again following
      cessation of lactation. Unexpectedly, BMD in the lumbar spine, an asymptomatic
      site, was also markedly decreased at the time of presentation (31% lower than the
      mean of age-matched controls). Recovery of spinal density did not occur during
      the first year. However, spinal BMD did begin to increase during the second year
      and continued to rise after the cessation of lactation. In contrast to the marked
      reduction in bone density at these site of trabecular bone, cortical bone density
      in the forearm was normal. Possible aetiologies of pregnancy associated
      osteoporosis are discussed.

PMID- 7586610
TI  - Cushing's disease due to female gonadotroph adenoma of the pituitary.
AB  - A 39-year-old woman presented with amenorrhoea, hyperprolactinaemia and sellar
      mass. Bromocriptine normalized PRL levels but failed to suppress tumour growth.
      Subsequently, she developed clinical signs and elevated blood cortisol levels
      consistent with a diagnosis of Cushing's disease. A pituitary tumour was removed
      which was immunoreactive for ACTH. Electron microscopic examination, however,
      revealed a female gonadotroph adenoma indicating that adenoma cells regarded as
      gonadotrophs by ultrastructural analysis may occasionally secrete ACTH and cause
      Cushing's disease.

PMID- 7586611
TI  - TSH receptor antibodies and ultrasonography in Graves' disease.

PMID- 7586612
TI  - The role of vitamin D and calcium supplementation in the prevention of
      osteoporotic fractures in the elderly.

PMID- 7586615
TI  - Naloxone-induced ACTH release: mechanism of action in humans.

PMID- 7586614
TI  - Effects of gonadal androgens and oestrogens on adrenal androgen levels.
AB  - OBJECTIVE: The physiological role of adrenal androgens in humans remains unclear.
      Furthermore, there are few data on the relation between sex steroids and adrenal
      androgen production. We have assessed the effects of sex steroid hormone
      administration on adrenal androgen levels, by studying a large group of
      transsexual patients. DESIGN: A non-randomized intervention. SETTING: A
      university teaching hospital. PATIENTS: Thirty-one male-to-female and 22 female
      to-male transsexual patients. MEASUREMENTS: Plasma levels of adrenal androgens
      were measured in a group of male-to-female and female-to-male transsexual
      patients both before and during cross-gender hormone treatment. This treatment
      involves administration of testosterone esters to women and of ethinyloestradiol
      and cyproterone acetate to men. RESULTS: High dose sex steroid administration had
      marked effects on adrenal androgens levels, which decreased by 27-48% in males
      treated with ethinyloestradiol and increased by 23-70% in females treated with
      testosterone. CONCLUSION: We conclude that administration of high doses of
      testosterone and oestradiol exert opposing effects on adrenal androgen
      production.

PMID- 7586616
TI  - A comparison of the naloxone test with ovine CRH and insulin hypoglycaemia in the
      evaluation of the hypothalamic-pituitary-adrenal axis in normal man.
AB  - OBJECTIVE: It has been suggested that naloxone might be useful in clinical
      testing of the hypothalamic-pituitary-adrenal (HPA) axis. We have therefore
      evaluated this non-selective opioid receptor antagonist, as a test of HPA axis
      function, and compared the results to ovine corticotrophin-releasing hormone
      (oCRH) and the insulin tolerance test (ITT). DESIGN: Following i.v.
      administration at time zero of naloxone 20 mg (n = 12) on day 1, and either oCRH
      1 microgram/kg (n = 6) or soluble insulin 0.15U/kg (n = 6) on day 2, venous blood
      was sampled at times 120, 0, 15, 30, 45, 60, 90 and 120 minutes for cortisol,
      ACTH and AVP. Peripheral CRH was also measured following naloxone and insulin
      hypoglycaemia. SUBJECTS: Twelve normal males (age 20-57 years) with no history of
      hypothalamic-pituitary-adrenal axis disease. MEASUREMENTS: Peptide hormones in
      plasma samples were measured by radioimmunoassay and cortisol by ELISA. Results
      are expressed as mean +/- SEM. RESULTS: Following naloxone, there was a highly
      significant overall rise in ACTH (P < 0.0005) and cortisol(P < 0.0001), but 1 out
      of the 12 subjects failed to respond. This subject had a normal ACTH and cortisol
      response to oCRH, indicating normal pituitary-adrenal function. Peripheral levels
      of CRH also increased significantly following naloxone (P < 0.002), while AVP did
      not alter significantly (P = 0.38). Maximal levels of CRH were seen following the
      ACTH peak however, at a time when ACTH was returning to baseline. All six
      subjects who received oCRH had an increase in ACTH and cortisol, and the ACTH
      response to oCRH was greater that that to naloxone (P < 0.05). One subject who
      developed nausea and hypotension following oCRH had a large rise in AVP and very
      high levels of ACTH and cortisol. Following insulin each subject had symptomatic
      hypoglycaemia and significant rises in cortisol (P < 0.0001), ACTH (P < 0.0001),
      AVP (P < 0.0005) and CRH (P < 0.01) were seen. Both cortisol and ACTH responses
      to ITT were significantly greater than those to naloxone (P < 0.05 for each).
      CONCLUSION: The HPA axis response to naloxone is smaller in magnitude overall
      compared to oCRH or insulin hypoglycaemia and is variable in normal subjects.
      This variability probably reflects changes in central opioid tone rather than
      alterations in pituitary responsiveness to CRH. It is unlikely that the naloxone
      test will replace currently used clinical tests of HPA axis function,
      particularly in the setting of a possible ACTH deficiency, because some subjects
      wit ha normal HPA axis appear not to respond to naloxone. As the mechanism
      involved in the ACTH response to naloxone has not yet been defined with
      certainty, the naloxone test should not be regarded simply as a test of
      endogenous CRH release.

PMID- 7586617
TI  - Psychopathology in patients with endogenous Cushing's syndrome: 'atypical' or
      melancholic features.
AB  - OBJECTIVE: Prolonged elevations of glucocorticoids have been linked to the
      effective disturbances experienced by patients with Cushing's syndrome. Major
      depression has been most commonly reported in patients with endogenous Cushing's
      syndrome. The purpose of this study was to determine whether these patients
      experience melancholic or 'atypical' subtype depression and to determine
      relations between current psychological functioning and factors such as duration
      and severity of Cushing's syndrome. DESIGN AND PATIENTS: We examined 33 adult
      patients with documented Cushing's syndrome and 17 hospitalized, matched
      controls, using standardized structured interviews and tests. RESULTS: During the
      active phase of Cushing's syndrome (prior to and/or on admission), 66.7% of all
      patients reported histories meeting criteria for a psychiatric diagnosis. Of
      those with a diagnosis during Cushing's syndrome, 50% reported major depression.
      Upon presentation to this institution, atypical depression was the most common
      diagnosis involving 51.5% (n =17) of all enrolled patients. Of the 17 with
      atypical depression, 8 reported a co-morbid psychiatric disorder. The duration of
      Cushing's syndrome was an important factor in predicting whether patients sought
      psychological intervention or met criteria for psychiatric diagnosis. CONCLUSION:
      Patients with active endogenous Cushing's syndrome exhibit significant
      psychopathology expressed primarily by atypical depression. Longer duration of
      Cushing's syndrome may place them at increased risk of such psychopathology.

PMID- 7586613
TI  - Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of
      follicle growth.
AB  - BACKGROUND AND OBJECTIVE: The antiprogestin mifepristone has been shown to
      disrupt folliculogenesis and endometrial maturation and, therefore, has the
      potential to be used as a novel form of contraception. The purpose of this study
      was to investigate further the effects of daily administration of a low dose of
      mifepristone (2mg) on the ovarian cycle and on the dynamics of follicle growth.
      SUBJECTS: Six healthy female volunteers were given 2mg mifepristone daily for 30
      days following an ovulatory control cycle. MEASUREMENTS: Follicle growth was
      monitored with transvaginal ultrasonography and hormonal measurements in blood
      and urine were used to monitor effects on the ovarian cycle. In addition,
      concentrations of cortisol and ACTH in serum were measured to assess the effects
      of mifepristone on the pituitary-adrenal axis. RESULTS: Treatment with
      mifepristone retarded the follicular growth rate in all women (P = 0.01).
      Ovulation was inhibited in 4 of 6 subjects and appeared to be mediated through an
      effect on the hypothalamo-pituitary axis, as no surge of FSH or LH occurred. In
      these subjects the dominant follicle continued to grow and developed into a
      persistent follicle. In two cases the persistent follicle remained functional and
      ovulation occurred soon after stopping treatment. In the remaining two subjects,
      the dominant follicle developed into a non-functioning cyst ( > 30 mm) which
      persisted for one month after the end of the post-treatment cycle. In the two
      subjects who ovulated, the LH surge was delayed by 6 and 7 days but was followed
      by a luteal phase of normal length. There was no significant change in the
      concentration of ACTH or cortisol suggesting that treatment with mifepristone in
      this dose has little if any effect on the pituitary-adrenal axis. CONCLUSION:
      These findings add further evidence to support the contraceptive potential of
      mifepristone through effects on follicular development and on the menstrual
      cycle.

PMID- 7586618
TI  - 'Subclinical hypothyroidism': to treat or not to treat, that is the question.

PMID- 7586620
TI  - Ovarian morphology and insulin sensitivity in women with bulimia nervosa.
AB  - OBJECTIVE: Hyperinsulinaemia has a role in the development of hyperandrogenism
      and polycystic ovary syndrome in women of normal weight. Polycystic ovaries are
      common in women with bulimia nervosa and this study aimed to determine whether
      women with bulimia nervosa are insulin resistant and to examine the relation
      between insulin sensitivity and ovarian morphology. DESIGN: A short intravenous
      insulin tolerance test was used as a direct measure of insulin sensitivity in a
      group of women with bulimia nervosa and a control group. PATIENTS: A series of 12
      women with bulimia nervosa and normal weight was compared with a control group of
      9 healthy women who had no clinical signs of eating disorder or hyperandrogenism
      and did not have polycystic ovaries. MEASUREMENTS: Bulimic behaviour was assessed
      using the BITE (Bulimia Investigation Test, Edinburgh) questionnaire and clinical
      interviews. Ovarian morphology was assessed using transabdominal ultrasonography.
      Insulin sensitivity and serum insulin, fasting glucose, LH, FSH, prolactin,
      testosterone, androstenedione and sex hormone binding globulin (SHBG) were
      measured and compared between the two groups. RESULTS: Ten of the 12 women with
      bulimia nervosa underwent ovarian ultrasound examination and they all had
      polycystic ovaries. There was no difference in serum LH, FSH, testosterone,
      androstenedione of SHBG concentrations between the women with bulimia nervosa and
      the non-bulimic control group. Fasting blood glucose concentrations were normal
      in all the women studied and did not differ between the women with bulimia
      nervosa and the control women. There was also no difference in fasting serum
      insulin or insulin sensitivity between the women with bulimia nervosa and the
      nonbulimic women. CONCLUSIONS: Bulimia nervosa is not associated with insulin
      resistance and chronic hyperinsulinaemia.

PMID- 7586619
TI  - Elevated serum lipoprotein(a) in subclinical hypothyroidism.
AB  - OBJECTIVES: Asymptomatic lymphocytic thyroiditis and subclinical hypothyroidism
      are associated with increased risk for coronary artery disease. The present study
      aimed at evaluating serum lipoprotein(a)(Lp(a)), measured as apo(a), and other
      lipid parameters in 32 subjects with asymptomatic subclinical hypothyroidism.
      SUBJECTS: Thirty-two Chinese subjects with asymptomatic subclinical
      hypothyroidism were compared to 96 age and sex-matched healthy controls. RESULTS:
      Subclinical hypothyroid patients had higher (P < 0.005) apo(a), total
      triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol
      (LDL-C) but lower (P < 0.05) high density lipoprotein cholesterol (HDL-C) levels
      compared with sex and age-matched controls (apo(a) 296 (48-1650) vs 182 (19-1952
      U/l), geometric mean (range); TG 1.86 +/- 0.94 vs 1.33 +/- 0.74 mmol/l (mean +/-
      SD); TC 6.10 +/- 1.17 vs 5.42 +/- 1.13 mmol/l; LDL-C 4.10 +/- 1.00 vs 3.49 +/-
      0.96 mmol/l; HDL-C 1.15 +/- 0.40 vs 1.34 +/- 0.40 mmol/l, respectively). APo A-I
      and apo B were also higher than controls (1.96 +/- 0.48 vs 1.48 +/ 0.29 g/l and
      1.44 +/- 0.42 vs 1.05 +/- 0.29 g/l, respectively). Total cholesterol/HDL ratio
      and LDL/HDL ratio were also elevated in these subjects (5.77 +/- 1.96 vs 4.28 +/-
      1.19 and 3.89 +/- 1.41 vs 2.79 +/- 0.97, respectively, both P < 0.0005).
      Individual analysis revealed that 16 (50%) subjects had hyperlipoproteinaemia (TC
      > 5.2 mmol/l in 10; TC > 5.2 mmol/l and TG > 2.3 mmol in six) as compared to
      21(20.8%) in the control group (P < 0.005). Subjects with TSH > or = 11.0 mIU/l
      had significantly higher TC/HDL and LDL/HDL ratios. A significant correlation was
      observed between TSH levels and TC/HDL ratios (r = 0.455, P < 0.01). CONCLUSIONS:
      Subclinical hypothyroidism is associated not only with elevated LDL-cholesterol
      levels and low HDL-cholesterol levels but also with elevated lipoprotein (a).
      This may further increase the risk development of atherosclerosis.

PMID- 7586621
TI  - Dehydroepiandrosterone sulphate in critical illness: effect of dopamine.
AB  - OBJECTIVE: As part of a study on the effect of dopamine therapy on pituitary
      dependent hormone secretion in critical illness, we documented the impact of this
      inotropic and vasoactive catecholamine on the serum concentrations of
      dehydroepiandrosterone sulphate (DHEAS). Concomitantly, serum levels of PRL and
      cortisol were determined. PATIENTS AND DESIGN: In a prospective, randomized,
      controlled, open-labelled clinical study, 20 critically ill, adult polytrauma
      patients receiving dopamine treatment (5 micrograms/kg/mi i.v. for a median 109
      hours (range (21-296 hours)), were studied to evaluate the effect of dopamine
      withdrawal on serum concentrations of DHEAS, PRL and cortisol. The median age of
      the studied patients was 37 years (range 18-83 years). MEASUREMENTS: Serum DHEAS
      and cortisol concentrations were measured by RIA and PRL by IRMA. The assessed
      serum samples were obtained at 0300 h on each of two consecutive study nights.
      RESULTS: Withdrawal of dopamine infusion was found to elicit a median 25%
      increase of serum DHEAS concentrations within 24 hours whereas no significant
      change in DHEAS levels was observed when dopamine infusion was continued
      throughout both study nights (P = 0.01 continued vs interrupted dopamine).
      Prolactin levels were undetectable as long as dopamine was infused, and increased
      to a median of 317 IU/l after 24 hours of dopamine withdrawal (P = 0.0007).
      Elevated serum cortisol levels remained comparable with continued and interrupted
      dopamine infusion. CONCLUSIONS: Dopamine infusion appears to suppress serum DHEAS
      concentrations in critically ill patients without affecting their elevated serum
      cortisol levels, suggesting a differential regulation of DHEAS and cortisol
      metabolism in critical illness. The lowering effect of dopamine on DHEAS levels
      could be linked to the concomitant suppression of circulating PRL. The
      simultaneous suppression of circulating PRL and DHEAS by dopamine infusion may be
      an iatrogenic factor maintaining or aggravating the anergic state of prolonged
      severe illness.

PMID- 7586623
TI  - Childhood IQ measurements in infants with transient congenital hypothyroidism.
AB  - OBJECTIVE: In view of the fact that, during the first period of life, thyroid
      hormones are critical for brain development, we investigated whether even
      transient congenital hypothyroidism could affect the long-term intellectual
      development of affected infants. DESIGN: A case-control study of intellectual
      development, auxometric parameters and thyroid function performed in late infancy
      in children with documented transient congenital hypothyroidism or
      hyperthyrotrophinaemia at birth. PATIENTS: Nine children born in an endemic
      goitre area who had short-term transient congenital hypothyroidism or
      hyperthyrotrophinaemia after birth (TCH) were studied and compared to nine
      matched children born in the same area at the same time but having normal thyroid
      function at birth (N). MEASUREMENTS: Global, verbal and performance IQs were
      evaluated on the Wechsler scale. Height, bone age, total and free thyroid
      hormones, thyroid volume, thyroglobulin, basal and TRH stimulated TSH were also
      measured. RESULTS: Height and bone age were similar in the two groups. Thyroid
      function tests were also similar in the two groups except for basal and TRH
      stimulated serum TSH and serum Tg which were higher in the TCH than in the
      control group. Global, verbal and performance IQs were systematically lower in
      the TCH than in the N group. (78.3 +/- 11.1 vs 90.9 +/- 14.2, P < 0.05; 84.4 +/-
      15.4 vs 96.2 +/- 14.8, P NS; 75.0 +/- 8.5 vs 89.2 +/- 12.5, P < 0.01
      respectively). CONCLUSION: Infants born and living in an academic goitre area,
      who had biochemical signs of thyroid hypo-function at birth, had a lower
      intelligence quotient at the age of 7-8 years than matched controls living in the
      same environmental conditions but with normal thyroid function at birth. The
      present findings strongly suggest that abnormalities in thyroid function at
      birth, even when transient, can adversely affect long-term intellectual
      development.

PMID- 7586622
TI  - High prevalence and little change in TSH receptor blocking antibody titres with
      thyroxine and antithyroid drug therapy in patients with non-goitrous autoimmune
      thyroiditis.
AB  - OBJECTIVE: We have reevaluated the prevalence and pathogenetic importance of TSH
      receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and
      investigated the changes in TRBAb activities during thyroxine and antithyroid
      drug treatment. DESIGN: Serum TSH binding inhibitor immunoglobulin (TBII) and
      thyroid stimulation blocking antibody (TSBAb) were measured serially in all
      patients with non-goitrous autoimmune thyroiditis (AT) and measured monthly
      during methimazole treatment in 6 patients. PATIENTS: Ninety patients with non
      goitrous AT and 95 patients with goitrous AT were entered consecutively into this
      study. All patients with non-goitrous AT were treated with thyroxine and followed
      at intervals of 6 months for 2 years initially and then yearly intervals. The
      duration of follow-up was 1-8 years. Six patients from the TRBAb-positive non
      goitrous AT group who were treated with thyroxine were randomly selected and
      given additional treatments with methimazole (40 mg per day) for 6 months.
      MEASUREMENTS: Serum TBII was measured by a radioreceptor assay, TSBAb by using
      FRTL-5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by
      radioimmunoassay. RESULTS: The prevalences of TBII and TSBAb is non-goitrous AT
      were 47.8 and 58.9%, respectively, which were significantly higher than those in
      goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed
      persistent TBII and TSBAb activities during the thyroxine treatment for up to 8
      years. A high dose of methimazole (40 mg per day) did not affect the titres of
      TBII and TSBAb in 5 out of 6 patients with non-goitrous AT tested. However,
      antithyroid peroxidase and antithyroglobulin antibodies activities were
      significantly decreased during the methimazole treatment. CONCLUSION: The high
      prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may
      play a major role in the development of hypothyroidism and thyroid atrophy in the
      vast majority of patients with non-goitrous autoimmune thyroiditis. Most TRBAb
      activities are stable for at least 8 years and are now affected by thyroxine and
      antithyroid drug treatment.

PMID- 7586624
TI  - Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic
      features.
AB  - OBJECTIVE: Osteomalacia associated with adult acquired Fanconi's syndrome is
      thought to result from hypophosphataemia and relative 1,25-dihydroxyvitamin D
      deficiency. We have followed the clinical and diagnostic features of patients
      with osteomalacia associated with adult Fanconi's syndrome, with particular
      emphasis on their responses to treatment with calcium, phosphate and vitamin D.
      DESIGN: Retrospective Mayo Clinic case-note review from 1975 to 1994 and
      prospective follow-up study, combined with literature review. PATIENTS: Eleven
      patients (7 male, 4 female) were identified who satisfied criteria for diagnosis
      of osteomalacia and adult Fanconi's syndrome. Twenty-five additional patients
      were identified in a literature review from 1954 to the present. METHODS:
      Clinical history and physical examination, serum and urine bone and mineral
      parameter, X-ray radiography and iliac crest bone histomorphometry. RESULTS: All
      patients presented with typical symptoms of osteomalacia, including lower
      extremity or low back bone pain, and all had fractures, pseudofractures, and/or
      bone demineralization on X-ray radiography. Osteomalacia and Fanconi's syndrome
      were diagnosed concurrently in 10 patients, whereas osteomalacia preceded
      diagnosis of Fanconi's syndrome by 5 years in one patient. Pre-treatment bone
      biopsies in 9 of the 11 patients demonstrated increased osteoid surface, volume
      and width. In the one patient labelled with tetracycline prior to biopsy,
      mineralization lag time was prolonged at 111 days (normal 19.2 +/- 1.0 days).
      Hypophosphataemia, inappropriately low 1,25-dihydroxyvitamin D levels, renal
      insufficiency, and chronic acidosis due to bicarbonate leak and uraemia,
      contributed to the osteomalacia in these patients. Secondary hyperparathyroidism
      was present in two patients. Eight of the 11 patients with osteomalacia
      associated with Fanconi's syndrome had monoclonal disorders, including multiple
      myeloma or lymphoma, many of them manifest by light-chain proteinuria. Over a
      mean patient follow-up period of 46 months (range 1-239 months), patients
      responded symptomatically to calcium, phosphate, and vitamin D replacement
      typically within 1-6 months. In 8 patients in whom follow-up data were available,
      post-treatment serum phosphate and 1,25-dihydroxyvitamin D levels improved in the
      setting of stable mild renal insufficiency; only one patient developed end-stage
      renal failure after 20 years, suggesting that these patients do not invariably
      progress rapidly to renal failure. CONCLUSIONS: Regardless of the underlying
      cause, osteomalacia associated with adult acquired Fanconi's syndrome appears to
      respond well to calcium, phosphate, and vitamin D replacement. These patients do
      not appear to necessarily require 1,25-dihydroxyvitamin D replacement.

PMID- 7586625
TI  - Disturbed anabolic hormonal patterns in burned patients: the relation to
      glucagon.
AB  - OBJECTIVE: Complex changes in the anabolic regulators of metabolism occur after
      major injury. We have studied the time course for IGF-I and IGFBP-1 after burn
      injury and their relations to circulating levels of other anabolic and catabolic
      hormones. The hormonal patterns during the onset of sepsis were also
      investigated. PATIENTS: Eight patients (age 36 (6) years, mean (SEM)) with major
      burn injury (burn area 42 (6) %) were studied. The first 2 days since the burn
      were used for rehydration therapy (rehydration period), after which a complete
      total parenteral nutrition (TPN) period was initiated. Seven positive blood
      cultures, during the study period. Six of the eight survived. MEASUREMENTS: The
      hormonal changes determined in the morning during the first 7 days after the burn
      and from day 22 to 24 were investigated. The superimposed effects of sepsis were
      studied by normalizing all data to the day of positive blood cultures and
      clinical onset of sepsis. RESULTS: On admission, plasma levels of glucagon, IGFBP
      1 and GH were elevated while levels of IGF-I were low. During the first week
      after the burn, morning levels of glucagon and insulin increased while levels of
      GH and IGF-I decreased. GH levels were still elevated compared to healthy
      subjects. Despite the increase in insulin levels, IGFBP-1 remained elevated.
      Three weeks after the burn injury, IGF-I levels were increased but still markedly
      below normal, while IGFBP-1 levels remained unchanged. Persistent elevations of
      insulin levels were combined with reductions in glucagon levels. Admission levels
      of IGFBP-1 correlated to nitrogen loss (negative nitrogen balance) during the
      first 24 hours after the burn (r = 0.84, P < 0.05). A correlation between
      negative nitrogen balance and glucagon levels was found during early catabolic
      period in the rehydration period (i.e. days 2-3, r = 0.84, P < 0.01). The
      relative change in IGFBP-1 levels in the rehydration period correlated to changes
      in glucagon levels (days 2-3 vs admission, r = 0.85, P < 0.05). The
      insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both
      the rehydration period (days 2-3, r = 0.77, P < 0.05) and the third week after
      the burn (r = 0.77, P < 0.05). During the most catabolic phase in the first week
      after the burn (TPN period) there was an inverse relation between IGF-I and IGFBP
      I and glucagon (r = 0.83, P < 0.05). During the less catabolic third week after
      the burn, an inverse correlation was found between IGF-I and glucagon (r = -0.83,
      P < 0.05). Sepsis, superimposed upon the burn trauma, was associated with
      transient elevations in IGFBP-1 and reductions in insulin despite elevated levels
      of glucose and a further 50% increase in nitrogen losses. CONCLUSIONS: The
      present findings show that marked changes is important anabolic regulating
      factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the
      attenuation of the inhibitory effects of insulin on IGFBP-1, both contribute to
      the reduction in IGF-I levels and bioavailability, factors which may play an
      important role in post injury metabolism. Furthermore, these data suggest that
      the catabolic hormones (catecholamines, cortisol and glucagon), primarily
      glucagon seem to be involved in the modulation of IGF-I and IGFBP-1 levels
      following burn injury.

PMID- 7586626
TI  - IGFBP-3 is a poor parameter for assessment of clinical activity in acromegaly.
AB  - OBJECTIVE: Elevated serum IGF-I and IGF binding protein-3 (IGFBP-3) levels have
      been found in patients with active acromegaly. We have studied the relative
      diagnostic merits of measurements of IGFBP-3 compared with IGF-I as a parameter
      of disease activity in these patients. DESIGN/PATIENTS: Thirty untreated patients
      with acromegaly were compared with 30 healthy adults. MEASUREMENTS: Twenty-four
      hour sampling for serum GH in patients with acromegaly, serum IGF-I and IGFBP-3.
      RESULTS: Mean IGF-I levels were 22.0 nmol/l (range 6.5-38.4) in the healthy
      adults and 118.7 nmol/l (range 67.7-206.0) in patients with acromegaly. Mean
      IGFBP-3 levels were 3.5 mg/l (range 2.1-4.8) in controls and 5.4 mg/l (range 4.2
      6.6) in patients with acromegaly. Mean IGF-I/IGFBP-3 ratios were 6.5 nmol/mg
      (range 1.9-14.5) in the healthy adults and 22.0 nmol/mg (range 14.3-32.7) in
      patients with acromegaly. There was a considerable overlap for IGFBP-3 levels but
      not for IGF-I levels, between normals and acromegalics. The IGF-I/IGFBP-3 ratio
      also showed overlap between normals and acromegalics. There was a significant
      correlation between the mean 24-hour GH and IGFBP-3 levels (P = 0.036) and
      between the IGF-I and IGFBP-3 levels (P < 0.002) in acromegaly. In patients with
      acromegaly, the IGFBP-3 levels showed a decrement, but the IGF-I/IGFBP-3 ratio
      did not change significantly with age. CONCLUSIONS: IGFBP-2 has no additional
      discriminatory value over IGF-1 measurements for the assessment of clinical
      activity in acromegaly. In acromegaly, IGFBP-3 decreases with increasing age. In
      acromegaly, IGFBP-3 levels significantly correlate with mean 24-hour GH levels
      and IGF-I levels.

PMID- 7586627
TI  - Investigation of suspected hypothalamic diabetes insipidus.

PMID- 7586628
TI  - Familial prolactinoma.

PMID- 7586630
TI  - Pseudo-phaeochromocytoma and the serotonin syndrome.

PMID- 7586629
TI  - Primary hyperparathyroidism masked by antituberculous therapy-induced vitamin D
      deficiency.

PMID- 7586631
TI  - Whipple's disease.
AB  - Whipple's disease is a chronic systemic infectious disease caused by Tropheryma
      whippelii that typically involves the small intestine and causes malabsorption.
      Extraintestinal manifestations such as arthritis and fever are common and often
      exist prior to the onset of gastrointestinal symptoms. Involvement of the central
      nervous system can occur and lead to permanent sequelae. Weight loss,
      hyperpigmentation, and lymphadenopathy are frequent findings. The definitive
      diagnosis is made by biopsy of the small intestine mucosa which reveals
      infiltration of the lamina propria of the small intestine with periodic acid
      Schiff positive macrophages. Treatment with trimethoprim combined with
      sulfamethoxazole for 1 year usually results in clinical remission and an
      excellent prognosis. Recent advances using molecular techniques to identify the
      uncultured bacillus of Whipple's disease should lead to a better understanding of
      the pathophysiology and allow for the development of a sensitive noninvasive
      diagnostic test.

PMID- 7586632
TI  - Nonsteroidal anti-inflammatory drugs and gastrointestinal disease:
      pathophysiology, treatment and prevention.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common cause of
      gastrointestinal ulceration. Chronic NSAID use increases the risk of ulcer
      bleeding or perforation 3- to 4-fold. NSAID-induced injury results from both
      local effects and systemic prostaglandin inhibition. New evidence suggests that
      the systemic effects on prostaglandin production may vary between NSAIDs. The
      majority of NSAID-induced ulcers are asymptomatic. They may be treated by
      discontinuing the NSAID and using standard ulcer therapy. Patients taking NSAIDs
      who are at a high risk for a GI complication should also receive therapy to
      decrease their risk for ulceration. In this review the epidemiology,
      pathogenesis, risks, treatment and prophylaxis of NSAID-induced gastrointestinal
      complications are discussed.

PMID- 7586633
TI  - Acute cardiovascular complications of endoscopy: prevalence and clinical
      characteristics.
AB  - We sought to determine the prevalence of acute cardiovascular complications of
      endoscopy and to describe the clinical features associated with such events.
      Acute cardiovascular complications were identified from a computerized database
      of all endoscopies performed at our institution, and their clinical histories
      were abstracted from the medical records. Of 21,946 endoscopic procedures
      performed between August 1, 1988, and December 31, 1992, 9 women and 22 men
      (0.14%) developed acute cardiovascular complications including vasovagal reaction
      (24), supraventricular tachycardia (4), myocardial infarction (2) and congestive
      heart failure (1). Fourteen patients had underlying coronary artery disease and 4
      others exertional angina; 20 of 25 electrocardiograms available before the
      endoscopy were abnormal. Twenty patients required treatment during endoscopy, but
      only 3 needed continued therapy. One patient died of a periprocedural acute
      myocardial infarction. Seven (23%) patients experienced additional cardiac events
      during the follow-up period of 21.8 +/- 15.8 months. In conclusion, acute
      cardiovascular complications of endoscopy are infrequent and usually self
      limited; serious complications occurred exclusively in the setting of known
      underlying heart disease.

PMID- 7586634
TI  - Serum zinc concentrations in two cohorts of 153 healthy subjects and 100
      cirrhotic patients from Mexico City.
AB  - The aim of this study was to assess serum zinc levels in a cohort of healthy
      subjects and cirrhotic patients from Mexico City. A total of 153 healthy subjects
      and 100 cirrhotic patients, males and females aged 18-65, were studied. Inclusion
      criteria for healthy subjects were (1) Mexican-born with first and second
      generation relatives born in Mexico, and (2) somatometric (body mass index under
      30) and clinical evaluation establishing that they had no underlying disease.
      Entry criteria for cirrhotic patients were (1) clinical and histological proven
      cirrhosis, (2) compensated liver disease (absence of coma, bleeding hemorrhage or
      refractory ascitis), and (3) cirrhosis of any cause. Zinc serum levels were
      measured with atomic absorption spectrophotometry. In healthy subjects, mean
      serum levels were 77.4 +/- 4.2 micrograms/dl (range 42.9-105.2 micrograms/dl). In
      cirrhotic patients zinc serum levels (58.9 +/- 16.1 micrograms/dl, range 22-88
      micrograms/dl) were significantly lower than in healthy subjects (p < 0.05). A
      stepwise decline in serum zinc with worsening Child class (A, 73.4 +/- 13; B,
      64.4 +/- 12; C, 55.8 +/- 15.6; p < 0.05 by ANOVA test) was found. In conclusion,
      this study confirms that zinc serum levels are significantly lower in cirrhotic
      patients and shows that zinc serum levels in a cohort of 153 healthy subjects
      from Mexico City were unexpectedly lower compared to those found in other
      countries. This last finding might be explained by different dietetic patterns
      and deserves further investigation.

PMID- 7586635
TI  - Hepatocellular carcinoma: update on diagnosis and treatment.
AB  - In this review, the current approach to the screening, diagnostic evaluation,
      staging, and treatment for hepatocellular carcinoma (HCC) is outlined. The serum
      alpha-fetoprotein (AFP) level and abdominal ultrasonography (US) remain the
      cornerstones of screening protocols for HCC. Other serum marker proteins, such as
      abnormal serum prothrombin (PIVKA-II), when used in conjunction with AFP, can
      increase the yield for HCC. For diagnosis and staging of HCC, other imaging
      modalities employed include CT scan, infusion hepatic angiography, CT with
      arterial portography or iodized oil enhancement, MRI with contrast enhancement,
      intraoperative US, and US-guided fine-needle aspiration cytology and biopsy.
      Treatment options which have afforded some improvement in survival and tumor
      regression include surgical resection, orthotopic liver transplantation,
      percutaneous injection of ethanol, arterial chemoembolization, cryotherapy, and
      systemic or regional chemotherapy. Despite these advances, the diagnosis of HCC
      still portends a dismal prognosis.

PMID- 7586636
TI  - Nutritional support in inflammatory bowel disease.
AB  - Malnutrition is common in inflammatory bowel disease; deficiencies of multiple
      micronutrients and macronutrients can present a diagnostic and therapeutic
      challenge to the clinician. Enteral and parenteral nutrition have been used as
      adjunctive therapy to correct or prevent malnutrition in inflammatory bowel
      disease. In addition, some authors have advocated enteral and parenteral
      nutrition as primary therapy of acute inflammatory bowel disease. The efficacy of
      these nutritional therapies in the management of Crohn's disease and ulcerative
      colitis is reviewed.

PMID- 7586637
TI  - Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and
      cataract in two siblings--a new recessive syndrome?
AB  - Two siblings with atypical methylmalonic aciduria and progressive encephalopathy
      are reported. Initial symptoms were failure to thrive and growth retardation from
      the first year of life, progressing to severe mental retardation, microcephaly,
      dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in
      the urine was substantially lower than in classical methylmalonic acidemia and
      was not reduced by vitamin B12 therapy. The activity of methylmalonyl-CoA mutase
      and the overall assay of propionic acid metabolism in cultured fibroblasts were
      normal. The primary defect in this probably new autosomal recessive disorder
      associated with methylmalonic aciduria is currently not known.

PMID- 7586639
TI  - Health care utilization and perceptions of health among adolescents and adults
      with Turner syndrome.
AB  - We surveyed women aged 12 years and older who are members of the Turner Syndrome
      Society of the United States in regard to their health history, current health
      status, and health care utilization practices to identify the range of health
      problems and health care practices in this group. The mean age at diagnosis was
      10.8 years, and an endocrinologist (41%) or pediatrician (35%) was most likely to
      make the initial diagnosis. Individuals over age 35 years were diagnosed with
      Turner syndrome and begun on estrogen replacement therapy at a significantly
      older age than those who were in younger age groups. Seventy-five percent of the
      respondents had required some type of surgical procedure, and 14% had been
      hospitalized within the previous year. Ninety-four percent of women rated their
      overall health as good to excellent, while 6% rated it fair to poor. In the 12-17
      year age group, 89% of the young women were either currently taking or had
      previously taken growth hormone. The prevalence of major depressive symptoms was
      slightly higher than the general population for adolescents but similar to the
      general population for adults. For adult respondents, ratings of fair to poor
      health were significantly associated with increased outpatient visits. Growth
      hormone use was significantly associated with increased visits in the adolescent
      population. Based on these data, it appears that the clinical care of individuals
      with Turner syndrome has improved, but that they continue to have relatively high
      hospitalization rates and utilization of subspecialty services. Despite these
      health problems, most respondents demonstrated good adjustment as determined by
      standardized mental health measures.

PMID- 7586638
TI  - A search for three known RYR1 gene mutations in 41 Swedish families with
      predisposition to malignant hyperthermia.
AB  - Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel
      of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very
      closely linked to malignant hyperthermia susceptibility in man and are regarded
      to be causative. We have examined 41 Swedish families where malignant
      hyperthermia had occurred in at least one member during anaesthesia, with respect
      to three of the known mutations. The mutations were Arg163Cys; Ile403Met and
      Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families
      we detected the Arg614Cys mutation, and this was the only one of the mutations
      searched for that was observed. This indicates that other mutations than those
      searched for in this study must cause malignant hyperthermia susceptibility in
      most Swedish malignant hyperthermia susceptible families.

PMID- 7586642
TI  - Lung hypoplasia and severe pulmonary hypertension in an infant with double
      heterozygosity for spondyloepiphyseal dysplasia congenita and achondroplasia.
AB  - A rare instance of double heterozygosity for spondyloepiphyseal dysplasia
      congenita and achondroplasia is presented. Despite midface hypoplasia, thorax
      deformity and lung hypoplasia, the child survived the neonatal period. Severe
      pulmonary hypertension, already present at birth, led to right heart failure and
      death at the age of 1 year.

PMID- 7586641
TI  - Clinical traits and molecular findings in 46,XX males.
AB  - 46,XX maleness is characterized by the presence of testicular development in
      subjects who lack a Y chromosome. The majority of affected persons have normal
      external genitalia, but 10-15% show various degrees of hypospadias. Several
      hypotheses have been proposed to explain the etiology of this constitution:
      translocation of the testis-determining factor (TDF) from the Y to the X
      chromosome, mutation in an autosomal or X chromosomal gene which permits
      testicular determination in the absence of TDF, and undetected mosaicism with a Y
      bearing cell line. We report the phenotypic data and results of molecular
      analyses performed in six sporadic Mexican males with 46,XX karyotype. Molecular
      studies revealed Yp sequences in two individuals (ZFY+ SRY+) with different
      phenotypes, a third one presented with a smaller segment of Yp (ZFY- SRY+) and
      complete virilization, while the remaining three were Y-negative and showed
      hypospadias. In all subjects a hidden mosaicism with a Y-bearing cell line was
      ruled out due to the absence of Y-centromeric sequences. Our data demonstrate
      that the phenotype does not always correlate with the presence or absence of Y
      sequences in the genome, and confirm that 46,XX maleness is a genetically
      heterogeneous condition.

PMID- 7586643
TI  - Interstitial deletion of 8p: report of two patients and review of the literature.
AB  - Two female infants with de novo interstitial deletions of 8p were studied. One
      with a deletion from p11.21 to p11.23, and the other patient with a deletion from
      p11.23 to p21.3 had several clinical manifestations of the terminal 8p- syndrome.
      Band 8p11.23 was deleted in both patients. The clinical manifestations common to
      both patients included low birthweight, growth deficiency, congenital heart
      disease, mental retardation, dolichocephaly, low-set, malformed ears, high-arched
      palate, thin lips and micrognathia. Since these features may occur in most
      patients with chromosomal imbalance, and the terminal 8p- syndrome has hitherto
      been assumed to result from terminal deletions of 8p, ranging from p21.3 to p23,
      it is likely that these features are simply related to the chromosomal imbalance
      rather than to band specific imbalance of 8p11.23. The present study suggests
      that two different types of deletion, interstitial and terminal, are associated
      with still poorly defined, rather non-specific clinical features.

PMID- 7586640
TI  - Complexity of molecular genetics of dyslipidemia in a family highly susceptible
      to ischemic heart disease.
AB  - In a Danish family highly susceptible to ischemic heart disease, hyperlipidemia
      did not simply cosegregate with a previously undescribed 10 bp deletion in the
      LDL receptor gene causing heterozygous familial hypercholesterolemia (FH). This
      mutation, designated as FH DK-4, deletes 10 nucleotides from exon 4 coding for
      the third cysteine-rich repeat of the ligand-binding domain. The resulting
      translational frameshift and stop codon corresponding to amino acid position 181
      in the LDL receptor cDNA is predicted to result in a truncated LDL receptor
      protein. Several family members had hyperlipidemia and early onset of ischemic
      heart disease not due to the 10 bp deletion, and several family members had
      unexpectedly high serum lipoprotein(a) contributing to high concentrations of
      serum LDL cholesterol. The study illustrates important limitations and
      possibilities of molecular genetic diagnosis.

PMID- 7586644
TI  - Identification of a CD40L gene mutation and genetic counselling in a family with
      immunodeficiency with hyperimmunoglobulinemia M.
AB  - A 13-year-old boy with immunodeficiency with hyper-IgM was analyzed for mutations
      in the CD40L gene. An insertional mutation of an extra T in a run of four T's was
      found in the second exon of the gene, leading to a premature translation stop.
      Genetic counselling of the family was performed, based on mutation detection by
      PCR/oligohybridization.

PMID- 7586645
TI  - Molecular characterization of trisomic segment 3p24.1-->3pter: a case with review
      of the literature.
AB  - A 1-year-old male infant was found to have a de novo unbalanced translocation,
      resulting in trisomy for a portion of the short arm of chromosome 3, i.e.
      46,XY,der(7)t(3;7) (p24.1;p22). Previous cases with a so-called "trisomy 3p
      syndrome" were evaluated by GTG banding, while we attempted to characterize the
      present case by the FISH-technique. The major clinical features included:
      dysmorphic ears, decreased muscle tone and seizure episodes associated with
      fever, which are concordant with "trisomy 3p syndrome". The most common
      malformations of trisomy 3p syndrome are: psychomotor and mental retardation,
      short neck, hypertelorism/telecanthus and congenital heart defects.
      Predominantly, the 3p trisomies have been maternally derived and the major
      mechanism of inheritance is due to a malsegregation of the chromosomes that are
      involved in a parental balanced translocation. A review of 44 cases from 35
      studies revealed that the clinical manifestations have been quite varied,
      depending upon the amount of 3p2 material in the trisomic state, but
      interestingly a recognizable pattern of features was obvious in those cases whose
      cytogenetic findings and clinical histories were known.

PMID- 7586646
TI  - Aarskog syndrome: severe neurological deficit with spastic hemiplegia resulting
      from perinatal cerebrovascular accidents in two non-related males.

PMID- 7586648
TI  - Congenital heart disease in the 48,XXYY syndrome.
AB  - We report on an infant with severe tetralogy of Fallot, bilateral preauricular
      pits, and a 48,XXYY chromosomal complement. This case and evidence collected from
      the literature suggest that congenital heart disease may occur in the 48,XXYY
      syndrome more frequently than currently appreciated.

PMID- 7586647
TI  - Parental origin of the X chromosome, X chromosome mosaicism and screening for
      "hidden" Y chromosome in 45,X Turner syndrome ascertained cytogenetically.
AB  - Our study confirms the finding that about 85% of X chromosomes in Turner girls
      are maternally derived. A new observation is the detection of a high frequency of
      mosaicism (15%) in Turner girls who by cytogenetic analysis were thought to have
      a pure 45,X karyotype. DNA examination of the material was done by hybridization
      with digoxigenin labelled, non-radioactive probes, and PCR products for
      microsatellite analysis were run on polyacrylamide gels. We screened for the
      presence of "hidden" Y chromosome mosaicism, using the primers SRY, ZFY, DYZ3,
      DYZ1 and DYS132. Contrary to other reports using the PCR technique to unravel
      "hidden" Y chromosome mosaics, we did not find any positive cases. A precise
      technical protocol for these new techniques is given, and the advantages are
      discussed.

PMID- 7586649
TI  - Clinical and molecular analysis of a Japanese boy with Morquio B disease.
AB  - Morquio B disease was found in a 15-year-old Japanese boy who presented with
      progressive generalized skeletal dysplasia without neurological manifestations.
      Mild keratan sulfaturia was found, and beta-galactosidase was deficient in
      fibroblasts. Gene analysis revealed two mutant alleles, 83Tyr-->His (Y83H) and
      482Arg-->Cys (R482C). The former expressed a low enzyme activity (2-5% of
      normal), and the latter expressed no detectable enzyme activity.

PMID- 7586651
TI  - The concurrence of the blepharophimosis, ptosis, epicanthus inversus syndrome
      (BPES) and Langer type of mesomelic dwarfism in the same patient. Evidence of the
      location of Langer type of mesomelic dwarfism at 3q22.3-q23?

PMID- 7586650
TI  - The PvuII restriction site in the second intron of the human steroid 21
      hydroxylase gene CYP21 is polymorphic.

PMID- 7586652
TI  - Vitamin D dependent rickets type II and normal vitamin D receptor cDNA sequence.
      A cluster in a rural area of Cauca, Colombia, with more than 200 affected
      children.
AB  - Vitamin D dependent rickets type II is an autosomal recessive disease caused by
      the vitamin D defective receptor. More than 200 patients with different types of
      lower limb deformities were detected in a rural area of the Cauca department in
      the southwest part of Colombia. Patients were well nourished and in good physical
      condition in spite of their deformities. None of them presented alopecia,
      myopathy, seizures or aminoaciduria. Serum analysis showed significantly lower
      serum calcium as compared to normal relatives, though in the normal low range,
      normal phosphorus, high alkaline phosphatase, normal 25-hydroxyvitamin D3 and
      high 1,25-dihydroxyvitamin D3, indicating target organ resistance. The cDNA
      analysis showed normal nucleotide sequence. We suggest that our patients
      represent a distinct form of receptor-positive resistance to vitamin D. This
      report is the first extensive study on this class of patients.

PMID- 7586653
TI  - Tracheoesophageal anomalies in oculoauriculovertebral (Goldenhar) spectrum.
AB  - Tracheoesophageal fistula, with or without esophageal atresia (TEF/EA) appears to
      be a defect of blastogenesis, as is the oculoauriculovertebral (Goldenhar)
      spectrum (OAVS), with which it has occasionally been associated. We reviewed the
      records of all OAVS patients evaluated through the University of South Florida
      Regional Genetics Program between 1985 and 1993. Of 60 OAVS patients, three had
      TEF/EA. These results suggest that TEF/EA in association with OAVS is
      underreported. The occurrence of TEF/EA should prompt a thorough search for other
      known anomalies of OAVS.

PMID- 7586654
TI  - Monozygotic twins concordant for Rubinstein-Taybi syndrome: changing phenotype
      during infancy.
AB  - We describe monozygotic twin sisters concordant for Rubinstein-Taybi syndrome
      diagnosed at the age of 10 weeks. The typical features of Rubinstein-Taybi
      syndrome in early infancy increasingly developed towards the total "Gestalt" at
      the age of 2 years and 10 months.

PMID- 7586655
TI  - Opitz BBBG syndrome: new family with late-onset, serious complication.
AB  - The Opitz BBBG syndrome is characterized by hypertelorism and (in male patients)
      hypospadias, in addition to a number of midline abnormalities: posterior
      laryngeal cleft, stridor, swallowing dysfunction, cardiac defects, imperforate
      anus, and urinary tract and CNS anomalies. Inheritance is autosomal dominant
      (McKusick number *145410) with partial male sex limitation in most pedigrees. We
      report a Dutch family with Opitz BBBG syndrome in which the proband developed
      late-onset symptoms of a structural laryngeal abnormality.

PMID- 7586656
TI  - Southern analysis reveals a large deletion at the hypoxanthine
      phosphoribosyltransferase locus in a patient with Lesch-Nyhan syndrome.
AB  - Whole genomic hprt clones were used in Southern analysis to screen the integrity
      of the hprt gene in a family that includes a patient with HPRT enzyme deficiency
      causal to Lesch-Nyhan syndrome. A 5 kb DNA sequence deletion was found to have
      its endpoints in the first and third introns. The probes identified the carrier
      status of female family members, aided by an RFLP carried by the mother's normal
      X-chromosome.

PMID- 7586657
TI  - Noonan syndrome with cafe-au-lait spots and multiple lentigines syndrome are not
      linked to the neurofibromatosis type 1 locus.
AB  - Noonan syndrome, multiple lentigines syndrome (LEOPARD syndrome), Watson syndrome
      and neurofibromatosis type 1 share certain clinical manifestations. We present a
      linkage analysis using microsatellite markers located in the neurofibromatosis
      type 1 region at 17q11 in a family with Noonan syndrome and cafe-au-lait spots
      and in another family with multiple lentigines syndrome. No linkage of the
      disease to the neurofibromatosis type 1 locus was found in the families
      investigated. On the basis of our results, we suggest that neither familial
      multiple lentigines syndrome nor Noonan syndrome is caused by a defect in the
      neurofibromatosis type 1 gene.

PMID- 7586659
TI  - Population frequency of apolipoprotein E5 (Glu3-->Lys) and E7 (Glu244-->Lys,
      Glu245-->Lys) variants in western Japan.
AB  - Apolipoprotein (apo) E modulates the catabolism of chylomicrons and of very low
      density lipoprotein remnants. It has three major isoforms (apo E2, E3, E4) and
      some rare variants. To detect the variants of apo E, blood specimens from 1269
      Japanese subjects were analyzed using isoelectric focusing with immunoblotting.
      The E5 and E7 variants were identified by IEF in 2 and 18 subjects, respectively.
      Both E5 (Glu3-->Lys) carriers were confirmed by PCR-mediated site-directed
      mutagenesis, and all E7 (Glu244-->Lys, Glu245-->Lys) carriers were confirmed by
      the amplification refractory mutation system. The relative frequencies of the
      epsilon 5 and epsilon 7 alleles were 0.001 and 0.007, respectively. High
      concentrations of total cholesterol (> 220 mg/dl) were detected in five of the
      subjects expressing apo E7 and one subject expressing apo E5, and eight subjects
      heterozygous for apo E7 showed elevated plasma triglyceride concentrations (> 150
      mg/dl). In 621 healthy subjects, the mean triglyceride concentration in subjects
      with apo E7/3 appeared to be higher than in those with apo E3/3, but the
      difference was not statistically significant.

PMID- 7586658
TI  - Identification of the valine 408 to methionine mutation in the LDL receptor in a
      Greek patient with homozygous familial hypercholesterolemia.
AB  - We have identified the cytosine to thymine change in the codon for amino acid 408
      which causes valine to be replaced by methionine in exon 9 of the LDL receptor
      gene in a 12-year-old Greek boy living in Germany, with homozygous familial
      hypercholesterolemia, by using polymerase chain reaction-amplified genomic DNA
      and subsequent restriction digestion. Homozygosity was confirmed by direct DNA
      sequencing. The mutation was present in both his parents, and his brother,
      grandmother, uncle and cousin. Six restriction fragment length polymorphisms of
      the LDL receptor gene were used to determine the haplotype of the defective
      allele. The haplotype was different from the one reported earlier in African
      Afrikaners and from Holland. We conclude that the mutation in the Greek boy
      probably occurred as an independent mutation. Because the parents are from
      different areas in Greece, this mutation may be common in Greeks.

PMID- 7586661
TI  - The mystery of one red ear.
AB  - Flushing and a sensation of tightness or pain in one ear lobe was a presenting
      complaint of 3 patients. In one case the symptoms were confined to the ear,
      another was associated with sensory impairment in the distribution of the C2 and
      C3 segments, while the 3rd patient experienced discomfort in the area of the 1st
      division of the trigeminal nerve on the same side. Two out of 3 patients had
      evidence of hypertrophy of the ipsilateral C2-3 facet joint and the symptoms of
      the 3rd patient were improved by an ipsilateral C2-3 root block. A possible
      mechanism could be the antidromic release of vasodilator peptides from afferent
      nerve terminals in response to irritation of the C3 root which supplies sensory
      innervation to the pinna.

PMID- 7586660
TI  - The understanding of epilepsy across three millennia.
AB  - The phenomena of epilepsy have been known for at least 3000 years, the earliest
      recorded account being in an Akkadian text called the Sakikku (written around
      1067-1046 BC). Over nearly all the subsequent centuries the popular belief has
      been that epilepsy is a disorder of supernatural origin, and to some extent such
      ideas have carried over into medical thought. In Western civilisation, the long
      dominant belief was that epilepsy was due to possession by a devil or a demon, an
      interpretation given authoritative support by the miracle story of the cure of
      the epileptic child which is recorded in all three synoptic Gospels. However,
      there have been many other interpretations e.g. epilepsy as a consequence of
      wrong doing or of lunar or magical influences. Such ideas began to die out only
      in the past 200 years. From Hippocrates (c. 400 BC) onwards, there has been a
      continuing line of thought that considered epilepsy a medical condition due to
      natural causes. The hypotheses concerning its pathogenesis have ranged from
      excess phlegm in the brain, through boiling up of the vital spirits in the brain
      (Paracelsus), explosion of the animal spirits in the centre of the brain
      (Willis), heightened reflex activity at a spinal (Marshall Hall) or medullary
      level (Brown Sequard), to Hughlings Jackson's notion of an occasional, an
      excessive, and a disorderly discharge' in part of the cerebral cortex. Among
      thinking men, epileptology in the past century has proved largely to be a matter
      of exploring the ramifications of Jackson's concepts.

PMID- 7586662
TI  - Insulin sensitivity and sensory nerve function.
AB  - The central and peripheral nervous systems do not require insulin for glucose
      uptake. However, insulin receptors have been detected in these regions. The aim
      of this study was to examine peripheral sensory nerve function and its dependence
      on insulin using healthy non-diabetic control subjects, obese individuals, and
      diabetic (insulin dependent and non-insulin dependent diabetes mellitus)
      subjects. The results revealed that the warm and cold perception thresholds,
      reflecting the functional states of unmyelinated C-fibres and A-delta fibres
      respectively, increased with reduced insulin sensitivity and with increased
      fasting insulin concentrations. From such data in non-diabetic subjects with
      measured insulin sensitivity, it appeared that sensory nerve function was
      disturbed in normoglycemic but insulin resistant states, suggesting that insulin
      has an action on nervous tissue in addition to its effects on glucose metabolism.
      The mechanisms of this action remain to be elucidated.

PMID- 7586663
TI  - Response to L-dopa and evolution of motor fluctuations in the early phase of
      treatment of Parkinson's disease.
AB  - Twenty patients with Parkinson's disease were studied during the early phase of L
      dopa treatment to clarify the development and progression of Parkinsonian motor
      fluctuations. Two patients had developed symptomatic motor fluctuations of
      moderate severity and another 3 had mild fluctuations. Both the initial response
      to L-dopa and the amplitude of response to a L-dopa test dose after a mean follow
      up period of 30 months were significantly greater for the fluctuating patients
      compared with those without fluctuation (p < 0.05). Although severe motor
      fluctuations do not usually develop until a number of years of L-dopa treatment
      have elapsed, this study shows that motor fluctuations can be detected quite
      early in the disease course and tend to appear in those patients who respond best
      to L-dopa.

PMID- 7586664
TI  - Huntington's disease in Hong Kong Chinese: epidemiology and clinical picture.
AB  - In a territory-wide survey of Huntington's disease (HD) in the Chinese population
      of Hong Kong, 20 patients from 11 families were identified from 1984 to 1991,
      giving a low period prevalence of 3.7 per 10(6) population. Six patients had died
      by 1991, hence the point prevalence was even lower, being 2.5 per 10(6)
      population. The male to female ratio was 3:1. No paternal transmission effect on
      the age of onset was observed. Apart from these differences, the clinical and
      pathological features were similar to those seen in the West.

PMID- 7586665
TI  - Isaac's syndrome: report of a case responding to valproic acid.
AB  - Isaac's syndrome is an uncommon, but distressing, condition of spontaneous
      abnormal muscle activity caused by neuronal hyperexcitability possibly due to
      damage to slow potassium channels. The underlying aetiology may be peripheral
      nerve damage from a wide variety of causes, including autoimmune disease. We
      report a case that failed to respond to carbamazepine or phenytoin but responded
      dramatically to valproic acid. Thus, valproic acid may be an effective treatment
      for Isaac's syndrome where these other drugs have failed.

PMID- 7586667
TI  - Rhinocerebral mucormycosis presenting as periorbital cellulitis with blindness:
      report of 2 cases.
AB  - Two cases of rhinocerebral mucormycosis in elderly, non-ketotic diabetics who
      were initially diagnosed and treated for bacterial periorbital cellulitis are
      reported. Both presented with a short history of periorbital pain and swelling
      followed rapidly by complete ophthalmoplegia and blindness. By the time of
      correct diagnosis, both cases were advanced with lower cranial nerve involvement,
      CT evidence of ophthalmic artery and cavernous sinus thrombosis and, in one,
      internal carotid artery invasion (demonstrated on MR angiography) with resultant
      cerebral infarction. One patient was treated with intravenous amphotericin B but
      died within a few days. The second patient had aggressive surgical resection and
      survived with significant residual morbidity. These cases illustrate that
      mucormycosis should be excluded in any diabetic patient presenting with orbital
      cellulitis, especially when there is early visual loss. Early aggressive
      treatment with surgery and antifungal agents is often successful whereas the
      outcome is almost universally fatal when the diagnosis is delayed.

PMID- 7586668
TI  - Primary cerebral abscess due to Nocardia asteroides presenting as stroke.
AB  - Nocardial cerebral abscess, an uncommon condition, is usually secondary to a
      septic focus elsewhere in the body. We report a 44-year-old Chinese male patient
      who had primary nocardial cerebral abscesses due to Nocardia asteroides which
      presented with stroke-like episodes. He improved spontaneously between these
      episodes. The diagnosis was reached only after a contrast CT brain study and
      microbiological examination of specimens obtained during craniotomy. An early
      contrast CT study is important in avoiding any delay in diagnosis and treatment
      of this serious condition.

PMID- 7586666
TI  - Routine use of lamotrigine, a new anti-epileptic medication, and the value of
      measuring its blood levels.
AB  - Lamotrigine (LTG) has recently been approved for marketing in Australia as add-on
      therapy in resistant partial seizure disorders. Early reports cited a therapeutic
      blood level for LTG of 1-3 mg/L (4-12 mumol/L). Aspects of routine patient care
      with LTG, devoid of the restrictions of trial protocols, are discussed. Forty
      five patients commenced therapy but 15 discontinued LTG. Of the remaining 30
      patients, 9 became seizure free, 3 from the de novo trial in focal epilepsy and 6
      with generalised epilepsy. Global evaluation of patients showed mild to moderate
      improvement for those with focal epilepsy and moderate to marked improvement for
      those with generalised epilepsy. Blood levels of LTG did not provide clinically
      useful information.

PMID- 7586669
TI  - Alzheimer's disease and Alzheimer-type of cerebral degenerations in Chinese.
AB  - The incidence of Alzheimer's disease has been suggested to be low in Chinese but
      there have been few histological studies of the disease and of Alzheimer-related
      changes in Chinese. In this study, brains from 8 cases of Alzheimer's disease and
      27 non-demented elderly Chinese individuals were examined comprehensively.
      Dementia was excluded in the latter by careful retrospective interviews with
      relatives. Histological sections were taken from standardised areas and
      quantitative analysis of neuritic plaques, neurofibrillary tangles and diffuse
      plaques was carried out with 3 histological methods: microwave modification of
      Bielschowsky, Bodian and beta A4 protein immunostaining. There were conspicuous
      differences in the amounts of neurofibrillary tangles and neuritic plaques seen
      between the demented and non-demented groups. In the latter, the amount of
      Alzheimer-related changes appeared to be much smaller than in corresponding
      studies among Western populations. Diffuse plaques were not found to be a good
      histological marker for dementia.

PMID- 7586670
TI  - Mercury: god of Th2 cells?

PMID- 7586671
TI  - Accumulation of activated CD4+ lymphocytes in the lung of individuals infected
      with HIV accompanied by increased virus production in patients with secondary
      infections.
AB  - The lung is continuously exposed to infectious and non-infectious agents causing
      cell activation. Activated cells in the lung such as antigen-presenting cells
      which harbour HIV may favour this organ as a site for virus production. To test
      this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV
      infected patients and healthy controls were obtained and the activation of the
      cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA
      1. The HIV-infected individuals were subdivided into 'lung symptomatic' or 'lung
      asymptomatic' patients, depending on the presence or absence of secondary lung
      diseases besides HIV. All HIV-infected individuals demonstrated a decreased
      number of CD4+ lymphocytes in blood; however, normal numbers of these cells were
      found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and
      BAL was higher in lymphocytes from HIV-infected patients compared with controls.
      The activation state was highest in the lung symptomatic group. Lung symptomatic
      patients and lung asymptomatic patients with extrapulmonary infections had
      increased levels of free virus in plasma. Four out of four individuals without or
      with only low amounts of cell-free HIV in plasma belonged to the symptom-free
      subgroup. These results suggest that microorganisms other than HIV may promote
      viral replication via antigen-driven accumulation and activation of CD4+ cells in
      the lung or other organs, and thus may be responsible for the loss of helper T
      cells and the progression of the disease.

PMID- 7586672
TI  - Effect of HIV vertical transmission on the ontogeny of T cell antigens involved
      in the regulation of humoral immune response.
AB  - HIV infection causes progressive impairment of humoral immunity, including
      defective specific antibody production. To evaluate whether vertical HIV
      infection interferes with the expression on CD4+ lymphocytes of developmentally
      regulated molecules, that play a crucial role in the generation of immunological
      memory (CD45 isoforms) and in attainment of antibody responses (CD40L), 22 HIV
      infected children and 36 seroreverted children born to HIV+ mothers were studied.
      The percentage of CD40L+ PBMC after activation in vitro with phorbol myristate
      acetate (PMA) plus ionomycin was lower in HIV-infected children than in controls
      (P < 0.004). This correlated with the depletion of CD4+ lymphocytes (r = 0.75; P
      < 0.001). CD40L expression rose progressively with age (r = 0.36; P = 0.03) in
      seroreverted children, but not in HIV-infected children, suggesting that while in
      normal children in vivo antigen stimulation results in progressive attainment of
      CD40L expression (and thus to effective T-B cell cooperation), this process is
      largely defective in HIV-infected children, contributing to the genesis of
      humoral immune deficiency. The proportion of CD4+ cells bearing the CD45RO
      isoform was increased among HIV-infected infants during the first years of life.
      However, the percentage of CD4+ CD45RO+ peripheral blood mononuclear cells (PBMC)
      progressively increased with age in controls (r = 0.69; P = 0.03), but not in HIV
      infected children, showing that while vertical transmission of HIV does not
      prevent CD45RO expression early in life, it is associated with a disturbance of
      the physiological process of antigen priming, contributing to poor immunological
      memory to T cell-dependent antigens.

PMID- 7586673
TI  - In vitro stimulation of peripheral blood mononuclear cells (PBMC) from HIV- and
      HIV+ chancroid patients by Haemophilus ducreyi antigens.
AB  - The cellular immune responses to fractionated Haemophilus ducreyi antigens,
      coated on latex beads, were assessed in patients with chancroid and in controls,
      using an in vitro lymphocyte proliferation assay. Several fractions of H. ducreyi
      antigen revealed stimulating activity. However, only the molecular size ranges 91
      78 kD, 59-29 kD, and 25-21 kD induced proliferation that may be specifically
      related to H. ducreyi infection. Lymphocytes from four HIV- patients,
      successfully treated for chancroid, were not stimulated by H. ducreyi antigen. In
      general, lymphocytes from HIV+ chancroid patients were less responsive to H.
      ducreyi antigen compared with those from HIV- chancroid patients. However, two
      HIV-infected patients showed exceptionally strong responses to high molecular
      weight fractions. To our knowledge this is the first report demonstrating that H.
      ducreyi contains specific T cell-stimulating antigens. Based on this work,
      further identification and purification of the T cell antigens is feasible.

PMID- 7586675
TI  - Spontaneous proliferation of memory (CD45RO+) and naive (CD45RO-) subsets of CD4
      cells and CD8 cells in human T lymphotropic virus (HTLV) infection: distinctive
      patterns for HTLV-I versus HTLV-II.
AB  - Spontaneous lymphocyte proliferation (SLP) in vitro is a characteristic feature
      of about 50% of individuals infected with HTLV-I or HTLV-II. Both CD4 cells and
      CD8 cells contribute to SLP in HTLV-I infection, whereas SLP in HTLV-II infection
      is usually restricted to CD8 cells. In this study, we asked if SLP was restricted
      to the memory (CD45RO+) cell subset of CD4 and CD8 cells in HTLV infection.
      Purified CD4 and CD8 cells were separated into CD45RO+ and CD45RO- populations by
      a modified panning technique, and spontaneous proliferation (SP) of the cell
      subsets was assessed. For all five HTLV-I-infected persons whose mononuclear cell
      cultures were SLP+, only CD45RO+ cells, but not CD45RO- cells, within CD4 and CD8
      subsets showed SP. In contrast, five of six SLP+ HTLV-II+ individuals showed SP
      in both the CD45RO+ and the CD45RO- subsets of CD4 cells, and 10 of 12 SLP+ HTLV
      II+ individuals showed SP of both the CD45RO+ and CD45RO- subsets of CD8 cells.
      Polymerase chain reaction studies showed that proviral genome was generally
      present in both CD45RO+ and CD45RO- subsets of CD4 and CD8 cells, regardless of
      HTLV type and SP activity. These findings show that SP of both CD4 and CD8 cells
      in HTLV-I infection is usually restricted to CD45RO+ memory cells, whereas in
      HTLV-II infection, both CD45RO+ memory and CD45RO- naive subsets of CD4 and CD8
      cells may exhibit SP. It thus appears that HTLV-I infection and HTLV-II infection
      exhibit distinctive dysregulatory effects on memory and naive T cell
      subpopulations.

PMID- 7586674
TI  - Gamma delta T cells in rhesus monkeys and their response to simian
      immunodeficiency virus (SIV) infection.
AB  - Recent reports of the increase in peripheral blood gamma delta T cells in HIV+
      patients prompted us to examine the gamma delta T cell system in rhesus monkeys
      (Macaca mulatta) and the responses of these cells to SIV infection. Our results
      reveal differences in the gamma delta T cell subset composition and their
      expression of CD8 in the peripheral blood of monkeys and humans. The outgrowth of
      simian gamma delta T cells in response to Daudi cells is similar to that in
      humans, but the exposure to IL-2 stimulates preferentially the simian V delta 1
      subset rather than the V gamma 9/V delta 2 subset as found in humans. Upon SIV
      infection of the monkeys, we observed a transient increase of the percentage of
      total gamma delta T cell and the V gamma 9 subset. gamma delta T cells from
      infected animals also express more activation markers such as CD69, CD44 and the
      memory marker CD45RO. However, they respond to a lesser degree to Daudi or IL-2
      stimulation in the outgrowth experiments compared with uninfected animals,
      although the subset composition of total gamma delta T cells is similar in
      infected and uninfected animals. The results clearly indicate that gamma delta T
      cells in rhesus monkeys are influenced by SIV infection. The detailed analysis of
      the gamma delta T cell response to SIV infection can serve as a model for
      understanding human gamma delta T cell responses to HIV infections.

PMID- 7586676
TI  - Dengue virus-induced human cytotoxic factor: production by peripheral blood
      leucocytes in vitro.
AB  - During dengue type 2 virus (DV) infection of mice a unique cytokine, the
      cytotoxic factor (CF), is produced which reproduces the pathological lesions seen
      in patients of dengue haemorrhagic fever (DHF). Recently we have observed a CF
      like protein in the sera of DHF cases. The present study was undertaken to
      investigate whether DV can stimulate human peripheral blood mononuclear cells
      (PBMC) in vitro to produce human CF (hCF). Cultures prepared from PBMC or its
      enriched subpopulations were inoculated with 1000 LD50 of DV and controls with
      normal mouse brain suspension (NMB). Aliquots of cultures were harvested daily
      from 24 h to 96 h and their supernatant (CS) and cells were separated. CS were
      screened for viral titres and for the presence of hCF by cytotoxicity assay,
      inhibition ELISA, dot blot and Western blot tests using anti-mouse-CF antibodies.
      The RNA from the cells was screened in Northern blot and dot blot tests for the
      presence of mRNA for CF. It was observed that hCF appeared in the CS of DV
      infected culture of PBMC and T-enriched cells at 48 h and was present until 96 h;
      no CF was detected in CS of B cells or monocyte cultures. The production of hCF
      was abrogated by pretreatment of the T cells with anti-CD4 antibodies but not
      with anti-CD8 antibodies, indicating that hCF was produced by CD4+ T cells. The
      Northern blot analysis using oligonucleotide probes prepared on the basis of
      amino-terminal sequence of mouse CF, showed presence of mRNA for hCF in PBMC and
      T cell cultures. DV replicated in PBMC cultures with peak titres at 48 h. The
      findings of the present study demonstrate that DV-induced hCF is produced by
      human T cells.

PMID- 7586677
TI  - Circulating intercellular adhesion molecule-1 (ICAM-1) as an early and sensitive
      marker for virus-induced T cell activation.
AB  - The effect of systemic virus infection on the level of circulating ICAM-1 (cICAM
      1) in serum, and the role of virus-activated T cells in this context, were
      studied using the murine lymphocytic choriomeningitis virus infection as primary
      model system. A marked virus-induced elevation in cICAM-1 in serum was revealed,
      the presence of which coincided with the phase of virus-induced T cell
      activation. However, high levels of cICAM-1 in serum were observed well before
      maximal T cell activation could be demonstrated. No increase in cICAM-1 was
      observed in the serum of infected T cell-deficient nude mice, clearly
      demonstrating that T cells were mandatory. Analysis of MHC class I and MHC class
      II-deficient mice revealed that either CD4+ or CD8+ T cells alone are sufficient,
      despite a markedly reduced inflammatory exudate in the former animals. These
      results indicate that virus-activated T cells induce shedding of ICAM-1 into the
      circulation, and this parameter may be used as an early and sensitive marker for
      immune activation.

PMID- 7586680
TI  - Alterations in interleukin secretion (IL-2 and IL-4) by CD4 and CD4 CD45RO cells
      from common variable immunodeficiency (CVI) patients.
AB  - The failure of B cells from CVI patients to secrete normal amounts of antibodies
      has been attributed either to an intrinsic B cell defect or to a lack of
      cooperation from T cells. In an attempt to improve the definition of the origin
      of this defect in one of the main cellular compartments, we studied the ability
      of helper CD4 cells and their CD4 CD45RO subpopulation from CVI patients to
      secrete interleukins (IL-2 and IL-4) in response to mitogen stimulation. We found
      that CD4 and CD4 CD45RO cells from some patients secrete abnormal amounts of
      interleukins (in general low levels of IL-2 and high levels of IL-4) upon
      stimulation with pokeweed mitogen (PWM). These irregularities may contribute to
      the defective differentiation of B cells in these patients.

PMID- 7586678
TI  - The restricted IgG1 antibody response to maedi visna virus is seen following
      infection but not following immunization with recombinant gag protein.
AB  - Maedi-visna (MVV) is a retrovirus of the subfamily lentivirinae which includes
      HIV, simian immunodeficiency virus (SIV) and feline immunodeficiency virus (FIV).
      Infection of its natural host, the sheep, does not cause overt immunodeficiency,
      but rather a chronic inflammatory disease. However, subtle immunological changes
      following infection have been reported including a sheep IgG1 subclass-restricted
      MVV-neutralizing antibody. Here we demonstrate by Western blotting that there is
      no IgG2 serum antibody response to any MVV antigen after MVV infection, in
      contrast to infection with the parapox virus Orf, when serum IgG2 anti-Orf
      antibody is readily detected. By ELISA, the IgG1 antibody titres to Orf are
      higher than to MVV, but the minimum MVV serum antibody IgG1/IgG2 ratio is
      significantly raised compared with that for Orf virus antibody in the same sheep,
      indicating that the IgG2 defect in MVV infection cannot be accounted for by
      differences in the sensitivity of the Orf and MVV ELISA. Serum IgG2 anti-MVV gag
      p. 25 can be detected in both normal and MVV-infected sheep following
      immunization with purified recombinant MVV gag p 25 protein in Freund's complete
      adjuvant. The failure to make an IgG2 MVV-specific antibody indicates that
      immunological dysfunction can arise with macrophage tropic lentiviruses, and it
      may aid viral persistence.

PMID- 7586681
TI  - Fulminant meningococcal septic shock in a boy with combined inherited properdin
      and protein C deficiency.
AB  - A 7-year-old patient with fulminant septic shock due to Neisseria meningitidis of
      the uncommon serogroup Y developed extensive gangrene of the limbs. Multiple
      amputations were necessary and a pulmonary embolism occurred within 2 days post
      operatively. Complement and haemostatic system studies, done after recovery,
      showed a complete absence of properdin antigen and a low protein C antigen and
      activity level in plasma. Defective haemolytic activity in gel by the alternative
      pathway of complement activation could be restored with purified properdin,
      indicating a properdin deficiency type 1. Protein C antigen level as well as
      activity were in agreement with a protein C deficiency type I. The polymerase
      chain reaction (PCR) product of exon five of the protein C gene showed a
      substitution of 72Gly by Arg. Both deficiencies were traced among relatives of
      the patient. Serum of the father of the patient's mother was also properdin
      deficient. Microsatellite haplotyping of the X-chromosome of the patient and his
      relatives showed that a distinct haplotype cosegregated with the properdin
      deficiency (Lodscore 2.25; four informative meioses). The protein C type I
      deficiency was present in the patient's mother and her mother and cosegregated
      with the mutation found. So far as is known, this is the first patient described
      with combined inherited properdin deficiency and protein C deficiency.

PMID- 7586679
TI  - Immunological markers indicating the effectiveness of pharmacological treatment
      in human hydatid disease.
AB  - The relation of interferon-gamma (IFN-gamma), IL-4, IL-10 production and specific
      IgE, total IgG, IgG subclass expression to the effectiveness of pharmacological
      treatment in human hydatid disease (Echinococcus granulosus infection) was
      evaluated in 27 hydatid patients divided into four clinical groups according to
      their response to albendazole/mebendazole therapy (full, partial, low and non
      responders). After parasite antigen stimulation, peripheral blood mononuclear
      cells (PBMC) from full responders produced significantly more IFN-gamma (P =
      0.038), significantly less IL-4 (P = 0.001) and less IL-10 than PBMC from non
      responders. PBMC from partial and low responders produced intermediate cytokine
      concentrations. ELISA determining immunoglobulin production showed that sera from
      all non-responders had IgE and IgG4 antibodies, both regulated by IL-4. In
      contrast to IgG4, IgE decreased rapidly in full responders. Full responders also
      showed the highest percentage of IgG3 reactions. Qualitative analysis of total
      IgG responses in hydatid patients' sera determined by immunoblotting showed that
      binding profiles to hydatid cyst fluid antigen differed in the four groups of
      treated patients. Non-responders had the highest percentage of reactions to all
      subunits of antigens 5 and B, and full responders had the highest percentage of
      reactions to antigen 5 alone. The high IFN-gamma production associated with a
      lack of IL-4 and low IL-10 production in the full responders, and vice versa the
      high IL-4 and IL-10 production associated with lack of or low IFN-gamma
      production in the non-responders implies Th1 cell activation in protective
      immunity and Th2 cell activation in susceptibility to hydatid disease. IgE may be
      a useful marker of therapeutic success in hydatid patients with pretreatment
      specific IgE antibodies. IgG subclass responses and differential immunoglobulin
      subclass binding pattern to hydatid antigens may also be useful in the
      immunosurveillance of hydatid disease.

PMID- 7586682
TI  - Interferon-gamma (IFN-gamma) and IL-4 expressed during mercury-induced membranous
      nephropathy are toxic for cultured podocytes.
AB  - The subepithelial immune deposits of Dorus Zadel Black (DZB) rats with mercury
      induced membranous nephropathy consist of autoantibodies directed to laminin P1
      and of complement. The animals develop massive proteinuria within 10-14 days
      which is associated with obliteration of foot processes of glomerular visceral
      epithelial cells (GVEC), or podocytes. Previous studies indicate that these
      autoantibodies are probably not the sole mediator of proteinuria and GVEC damage.
      In this study we investigated whether circulating or macrophage-derived cytokines
      can contribute to the GVEC changes as detected in vivo. In vivo at the height of
      the proteinuria, increased intraglomerular IFN-gamma immunoreactivity was found.
      In diseased rats a five-fold increase in intraglomerular macrophages was found,
      but we could not detect intraglomerular IFN-alpha, IFN-beta, IL-1 beta or tumour
      necrosis factor-alpha (TNF-alpha) by using immunohistology. Subsequently, we
      exposed cultured GVEC to these cytokines to investigate their cytotoxic effects
      on several physiological and structural parameters. IFN-gamma and IL-4 were the
      only cytokines that exerted toxic effects, resulting in a rapidly decreased
      transepithelial resistance of confluent monolayers, which was closely associated
      with altered immunoreactivity of the tight junction protein ZO-1. IL-4 also
      affected vimentin and laminin immunoreactivity. IFN-gamma and IL-4 only
      interfered with monolayer integrity when added to the basolateral side of the
      GVEC, indicating specific (receptor-mediated) effects. Only IL-4 decreased the
      viability of the cells, and treated monolayers demonstrated an increased passage
      of the 44-kD protein horseradish peroxidase. From our experiments we concluded
      that IFN-gamma subtly affected monolayer integrity at the level of the tight
      junctions, and that IL-4 additionally induced cell death. We hypothesize that the
      toxic effects of the cytokines IFN-gamma and IL-4 as seen with cultured podocytes
      are necessary together with the autoantibodies, for the ultimate induction of
      proteinuria in mercury nephropathy in the DZB rat.

PMID- 7586684
TI  - Cytotoxic T cell responses in patients with chronic hepatitis B virus infection
      undergoing HBe antigen/antibody seroconversion.
AB  - Cytotoxic T cells have been identified in the peripheral blood of patients with
      acute hepatitis B virus infections for a short period after clinical
      presentation. However, in patients in whom the virus persists these have been
      difficult to demonstrate. In the chronic infection during HBe antigen clearance,
      when there has been an exacerbation of the disease, we have been able to
      demonstrate an MHC class I-restricted cytolytic response directed against the
      nucleocapsid antigens. In an HLA-A2 patient this was induced in vitro with the
      peptide p18-27, previously described as an HLA-A2-restricted T cell epitope. In
      patients of other HLA types, recombinant core antigen was used to induce antigen
      specific lysis: statistical analysis of the cytolytic responses of chronically
      infected patients demonstrated a nucleocapsid antigen-specific lysis in patients
      who were seroconverting. Removal of CD4+ cells reduced non-MHC-restricted
      cytolysis, allowing an MHC class I-restricted cytolytic component to be
      demonstrated.

PMID- 7586683
TI  - Significance of extractable nuclear antigens in childhood autoimmune liver
      disease.
AB  - Antinuclear antibody (ANA) is found in connective tissue disorders and in
      autoimmune liver disease. While ANA-positive connective tissue disorders are
      subdivided according to possession of specific antibodies to extractable nuclear
      antigens (ENA) (anti-ribonucleoprotein (anti-RNP), anti-Smith (anti-Sm), anti-Ro,
      anti-La), little is known about the presence and significance of ENA in
      autoimmune liver disease. To investigate this, we have tested 35 children with
      autoimmune hepatitis (AIH) (19 ANA and/or smooth muscle antibody-positive
      (ANA/SMA+ve); 16 liver kidney microsomal 1-positive (LKM-1 + ve)) and 14 with
      ANA/SMA+ve autoimmune sclerosing cholangitis (ASC), using both double dimension
      immunodiffusion and ELISAs. Eighty children with non-autoimmune liver disease (20
      alpha 1-antitrypsin deficiency, 20 Wilson's disease, 20 Alagille's syndrome and
      20 chronic hepatitis B virus infection) and 20 healthy controls were also tested.
      ENA were detected in seven (20%) patients with AIH: two ANA-positive, one SMA
      positive and four LKM-1-positive. Three were positive for anti-Sm, two for anti
      La, one for anti-Sm/anti-La and one for anti-Sm/anti-La/anti-Ro. ENA-positive had
      more severe liver disease than ENA-negative patients (P < 0.03). ENA were not
      detected in ASC, non-autoimmune liver diseases and controls. Our results indicate
      that ENA reactivity, including anti-Sm and anti-La, characteristic of systemic
      lupus erythematosus and Sjogren's syndrome, respectively, are present in some
      patients with AIH even in the absence of ANA, and may characterize a particularly
      severe form of the disease.

PMID- 7586686
TI  - Expression of vascular adhesion molecules on human endothelia in autoimmune
      thyroid disorders.
AB  - Cellular activation and expression of certain adhesion molecules within vascular
      endothelium is a critical event in leucocyte recruitment and emigration. A wide
      array of different adhesion receptors has been identified to mediate the
      interaction between endothelial cells (EC) and leucocyte subpopulations. In this
      study, the tissue expression of E-selectin, P-selectin, CD31, and endoglin
      endothelial cell adhesion molecules was studied on thyroid tissue from patients
      with Graves' disease (GD) and Hashimoto's thyroiditis (HT). We found an up
      regulated expression of E-selectin in EC in GD and HT thyroids, specifically in
      those areas more severely inflamed, with no reactivity in control thyroids. P
      selectin was basally expressed in postcapillary venules in control glands, with
      an increased expression in HT and GD glands. On the other hand, increased CD31
      expression was found on perifollicular, small and large venule EC from GD and HT
      glands, that correlated with the severity of mononuclear infiltration. In
      addition, CD31 expression was observed in some intrathyroidal macrophages and T
      cells in close proximity to CD31+ EC. Furthermore, a markedly enhanced expression
      of endoglin, a transforming growth factor-beta binding protein, was mainly
      located on perifollicular EC and EC from small venules as well as in adjacent
      macrophages from GD and HT thyroid glands. This enhanced expression of E- and P
      selectins, CD31 and endoglin by thyroid EC in GD and HT may reflect their ability
      to regulate leucocyte trafficking and activation.

PMID- 7586687
TI  - Insulin-like growth factor-1 (IGF-1) protects NOD mice from insulitis and
      diabetes.
AB  - To evaluate the effect of IGF-1 on the autoimmune process of beta cell
      destruction, permissive non-obese diabetic (NOD) recipients were adoptively
      transferred with 7 x 10(6) autoreactive T cells from diabetic NOD mice and were
      administered subcutaneously 10 micrograms rhIGF-1, twice daily for 3 weeks.
      Administration of rhIGF-1 reduced the final incidence of successful transfers of
      diabetes observed in only 6/24 mice (25%) versus 12/21 (57%) in control mice. A
      marked reduction of insulitis during histological analysis of pancreatic glands
      was also observed. Mice treated with rhIGF-1 had a higher percentage of intact
      islets (48.6 +/- 12% versus 1.6 +/- 1.1%, P = 0.001) and a lower percentage of
      infiltrated islets. Islets from rhIGF-1-treated mice had a more intense insulin
      staining reflecting a higher beta cell mass, but no difference was observed in
      the amount of insulin content of pancreatic extracts and in the amounts of mRNA
      transcripts for proinsulin. No difference was also observed in the titres of
      three islet cell antibody (ICA)-positive sera and in the pattern of A2B5
      staining. Some mice developed diabetes and severe islet cell infiltration despite
      rhIGF-1, thus indicating that some committed T cells were still able to invade
      the islets and cause beta cell destruction. The percentages of CD4+ and CD8+ T
      cells in the spleen of experimental mice were similar. To evaluate the effects of
      rhIGF-1 on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1,2
      mice injected into congenic NOD-N Thy-1,1 mice were monitored 3 weeks after
      adoptive cell transfer. The percentage of Thy-1,2+ T cells was significantly
      reduced in the spleen (10.8 +/- 1.3% versus 17.2 +/- 3.9%, P = 0.004) of rhIGF-1
      treated mice in contrast to the thymus (68.4 +/- 7.9% versus 72.87 +/- 6.2%, P =
      0.306), suggesting that rhIGF-1 could influence T cell trafficking to the
      lymphoid organs. The findings that rhIGF-1 has protective effects in autoimmune
      diabetes opens new perspectives for future experiments as well as for preventive
      strategies in human type I diabetes.

PMID- 7586688
TI  - Lupus-derived autoantibodies with dual autoactivity: anti-DNA and anti-Fc. I.
      Comparison of IgG autoreactivities with single-chain Fv derivatives.
AB  - Investigations into the intrinsic affinity and reactivity of autoanti-DNA active
      sites were initiated through the use of purified monoclonal IgG and the synthesis
      of single-chain Fv derivatives of murine monoclonal anti-DNA autoantibodies BV 04
      01 and BV 17-45. Results showed that relative to the respective IgG hybridomas,
      only the BV 04-01 SCA derivative showed demonstrable reactivity with DNA. The
      monovalent single-chain derivative of BV 17-45 showed no reactivity with DNA in
      solution or solid-phase assays, even though the parental IgG had been previously
      described as high affinity. However, 17-45 displayed reactivity as a bivalent
      single-chain derivative. In addition, upon concentration, BV 17-45 IgG formed a
      highly stable, papain-resistant precipitate. Investigations into the nature of
      the precipitate revealed that BV 17-45 possessed significant, DNA-inhibitable
      autobinding to its own IgG molecule. BV 04-01 also possessed similar anti-self
      reactivity. Thus, both monoclonal autoantibodies examined in this study possessed
      dual binding specificity; anti-DNa and anti-self.

PMID- 7586690
TI  - Anti-collagen antibodies in systemic sclerosis and in primary Raynaud's
      phenomenon.
AB  - The frequency and specificity of antibodies to native and denatured collagens
      were evaluated in systemic sclerosis (SSc) and in primary Raynaud's phenomenon
      (PRP) by direct and competitive ELISA. Antibodies reactive with denatured
      collagen type I (CI) were found in 43% of the SSc sera, and anti-CIV and anti-CV
      in 31%. In PRP, anti-CI, anti-CIV and anti-CV antibodies were detected in 8% of
      patient sera. Anti-CI, anti-CIV and anti-CV antibodies reacted with determinants
      expressed on the native as well as on the denatured molecule. Anti-CI and anti
      CIV were cross-reactive; a reactivity with CII and a lower one with CV were
      detected. Anti-CV antibodies also reacted with CI and CII and, in a smaller
      proportion of cases, with CIV. Anti-collagen antibodies, affinity-purified from
      blotted collagen IV and V and cyanogen bromide (CBr)-digested CI, displayed the
      cross-reactivities shown by inhibition studies on sera. Moreover, antibodies
      eluted from a CBr fragment of CI reacted with the other CBr fragments as well.
      These data show that one-third of SSc sera contain antibodies that react with
      epitopes expressed on native as well as on heat-denatured CI, CII, CIV and CV,
      and therefore have the potential to bind collagens in vivo.

PMID- 7586689
TI  - Lupus-derived autoantibodies with dual autoactivity: anti-DNA and anti-Fc. II.
      Fine specificity of anti-self autoreactivity.
AB  - The anti-immunoglobulin reactivity of two monoclonal, dual specific,
      autoantibodies, BV 17-45 and BV 04-01 was examined. The current study further
      defined the anti-immunoglobulin autoreactivity of these MoAbs to be Fc-specific.
      Both BV 17-45 and BV 04-01 bound their own Fc domains in addition to Fc regions
      of other MoAbs of similar isotype with varying levels of activity. The different
      anti-Fc reactivity patterns of BV 17-45 and BV 04-01 suggested that these MoAbs
      recognized distinct epitopes. Neither BV 17-45 nor BV 04-01 bound Fab fragments
      or single-chain antibody derivatives, which confirmed that the anti
      immunoglobulin reactivity of these autoantibodies was Fc-specific. In addition,
      abrogation of anti-Fc reactivity was observed when affinity-labelled MoAbs were
      used as coating antigens in solid-phase ELISAs. These results implied that active
      site ligand binding induced conformational changes which altered the Fc
      epitope(s) recognized by BV 17-45 and BV 04-01.

PMID- 7586685
TI  - CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to
      hepatitis C virus genotypes in chronic hepatitis C.
AB  - The pathogenic mechanisms that lead to chronic hepatitis C are unknown. As
      hepatitis C virus (HCV) has been shown to induce T cell response, we assessed
      whether a particular T lymphocyte subset could be preferentially detected in the
      liver of patients with chronic hepatitis C in relation to viraemia or HCV
      genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26
      patients by flow cytometry and immunohistochemistry. Viraemia was quantified by
      branched DNA assay. Using this assay, HCV RNA was not detectable in six patients.
      HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 x 10(6)
      Eq/ml. Genotyping was performed using a line probe assay. Type 1a, 1b, 2a, 3a and
      4a were found to infect 2, 10, 2, 7 and 3 patients, respectively. The CD4+/CD8+
      ratio of liver-derived lymphocytes was significantly higher (P < 0.01) in
      patients with detectable viraemia than in patients without detectable viraemia.
      In contrast, neither the percentage of gamma/delta T lymphocytes nor that of
      CD2+CD57+ cells was different in the groups. When comparing the CD4+/CD8+ ratio,
      the percentage of gamma/delta T lymphocytes or CD2+CD57+ cells according to
      genotype, the differences were not significant. These results suggest that the
      CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia but not to
      HCV genotypes in patients with chronic hepatitis C, and that T lymphocytes may be
      involved in the pathogenesis of liver lesions in chronic hepatitis C.

PMID- 7586692
TI  - Characterization and specificity of anti-endothelial cell membrane antibodies and
      their relationship to thrombosis in primary antiphospholipid syndrome (APS).
AB  - Immunoblotting was used to detect antibodies reacting with membrane and cytosol
      preparations of human umbilical vein endothelial cells (HUVEC), fibroblasts and a
      T lymphoma line HUT78 in 18 patients with anticardiolipin antibodies (ACA) (14 of
      whom had had a thrombotic event), 11 patients with a recent myocardial infarction
      and 17 controls. Multiple membrane-specific antibodies to HUVEC were found in 10
      of the patients with ACA (28 bands) and in nine of the patients with thromboses
      (27 bands) in contrast to only three of the patients with myocardial infarction
      (four bands) and one control (one band). The most frequently recognized HUVEC
      membrane epitopes were at 33 kD (four sera), 61-63 kD (five sera) and 76-79 kD
      (four sera). Although cross-reactivity with fibroblast and/or HUT78 membranes was
      seen at 33 kD, binding at 61-63 kD and 76-79 kD was specific for endothelial
      membranes. Although no correlations with the presence and titre of ACA were seen,
      HUVEC membrane-specific antibodies showed a correlation with venous thrombotic
      events.

PMID- 7586694
TI  - Allelic polymorphism in IL-1 beta and IL-1 receptor antagonist (IL-1Ra) genes in
      inflammatory bowel disease.
AB  - Recent reports have shown that allele 2 of the IL-1 receptor antagonist (IL-1Ra)
      gene is over-represented in ulcerative colitis (UC). Healthy individuals carrying
      allele 2 of this gene have increased production of IL-1Ra protein. Since the
      final outcome of the biological effects of IL-1 beta may depend on the relative
      proportion of these two cytokines, we have studied if a TaqI polymorphism in the
      IL-1 beta gene, which is relevant to IL-1 beta protein production, may be
      involved in the genetic susceptibility to UC and Crohn's disease (CD), in
      association with the established IL-1Ra gene polymorphism. Polymorphisms in the
      closely linked genes for IL-1 beta and IL-1Ra were typed in 100 unrelated Dutch
      patients with UC, 79 with CD, and 71 healthy controls. The polymorphic regions in
      exon 5 of the IL-1 beta gene and in intron 2 of the IL-1Ra gene, were studied by
      polymerase chain reaction (PCR)-based methods. The IL-1 beta allele frequencies
      in UC and CD patients did not differ from those in healthy controls. In order to
      study if the IL-1 beta gene polymorphism might participate synergistically with
      the IL-1Ra gene polymorphism in susceptibility to UC and CD, individuals were
      distributed into carriers and non-carriers of allele 2 of the genes encoding IL-1
      beta and IL-1Ra, in each of the patient groups and controls. Results indicated a
      significant association of this pair of genes, estimated by the odds ratio (OR)
      after performing Fisher's exact test, in the UC group (P = 0.023, OR = 2.81), as
      well as in the CD group (P = 0.01, OR = 3.79). Thus, non-carriers of IL-1 beta
      allele 2 were more often present in the subgroup of patients carrying the IL-1Ra
      allele 2. By contrast, no association of these alleles was detected in the group
      of healthy controls (P = 1.00, OR = 0.92). These results suggest that the IL-1
      beta/IL-1Ra allelic cluster may participate in defining the biological basis of
      predisposition to chronic inflammatory bowel diseases.

PMID- 7586691
TI  - Prevention of adoptive transfer of murine Sjogren's syndrome into severe combined
      immunodeficient (SCID) mice by antibodies against intercellular adhesion molecule
      1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1).
AB  - We have analysed the role of ICAM-1 and LFA-1 during development of autoimmune
      sialadenitis in MRL/lpr mice by direct analysis of RNA obtained from the salivary
      gland tissues, and the therapeutic effects with antibody administration on
      adoptive transfer system into SCID mice. The expression of cell adhesion
      molecules was assessed by using reverse transcriptase polymerase chain reaction
      (RT-PCR) and Southern blot analysis, and immunohistochemical analysis. Up
      regulated expression of ICAM-1 mRNA was observed before the onset of inflammatory
      lesions in the salivary glands at 1 month and 2 months old, and thereafter LFA-1
      mRNA was expressed within the typical inflammatory lesions, resembling human
      Sjogren's syndrome in MRL/lpr mice. Immunohistochemically, ICAM-1 was localized
      exclusively in the endothelial cells of varying sized blood vessels before the
      onset of disease, and LFA-1 expressing inflammatory cells were found within these
      lesions. When the therapeutic effects in vivo were examined, antibodies to ICAM-1
      in combination with anti-LFA-1 prevented adoptive transfer of Sjogren's syndrome
      in MRL/lpr mice into SCID mice, while no significant effect was found when
      treated with either antibody. These findings indicate that in Sjogren's syndrome
      like autoimmune lesions in MRL/lpr mice the ICAM-1/LFA-1 pathway may play a
      crucial role in the initiation and subsequent progression of T cell-mediated
      autoimmunity in the salivary and lacrimal glands of MRL/lpr mice.

PMID- 7586693
TI  - Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1
      (beta 2-GP1).
AB  - beta 2-GP1 is a serum protein which influences binding of anticardiolipin
      antibodies to cardiolipin, may influence induction of these antibodies in animals
      and may play a role in anticardiolipin-mediated thrombosis. Various investigators
      have proposed that when beta 2-GP1 binds cardiolipin, structural alterations
      occur in one or both molecules, resulting in exposure of new epitopes for
      anticardiolipin binding, but there has been no proof that such alterations occur.
      Utilizing Fourier transform infrared spectroscopy, this study analysed the
      structure of cardiolipin and beta 2-GP1 alone, then mixed with each other. For
      pure cardiolipin, analysis of the CH2 stretching, scissoring and carbonyl bands
      suggested this molecule assumes a hexagonal crystal lattice packing structure in
      both anhydrous and aqueous samples. Based on the second derivative analysis of
      the amide 1 band from the beta 2-GP1 protein backbone, as well as Fourier self
      deconvolution and curve fit algorithms, beta 2-GP1 was calculated to contain 18%
      turns, 37% alpha-helix, and 45% beta-sheet structure. beta 2-GP1 binding with
      cardiolipin results in a significant change in the conformation as well as
      geometry of the lipid and protein components. This is indicated by a broadening
      of the CH stretching band and a marked shift in intensity of the carbonyl band of
      cardiolipin, indicating less hydrogen bonding. There was a decrease in beta-sheet
      structure of beta 2-GP1 from 46% to 23% and appearance of 26% to 28% random
      structure. These findings indicate that mixing beta 2-GP1 with cardiolipin
      results in profound changes in both molecules which might explain the effect of
      beta 2-GP1 on anticardiolipin binding activity.

PMID- 7586695
TI  - Investigation of the complement receptor 3 (CD11b/CD18) in human rectal
      epithelium.
AB  - Rectal and cervicovaginal mucosa are common routes of transmission of HIV,
      although the mechanism of transmission is unknown. We have investigated human
      rectal and cervicovaginal epithelia for the expression of complement receptors
      (CR) and cell adhesion molecules which may be involved in HIV and other
      infections. In rectal mucosa, CR3 was detected in the surface and crypt
      epithelial cells by immunohistology, using MoAbs to CD18 and CD11b in 10 out of
      15 specimens. RNA transcripts encoding both CD11b and CD18 were also demonstrated
      in surface and crypt epithelial cells by in situ hybridization. Although CD11b
      was detected in the epithelial cells in three out of the 14 cervicovaginal
      specimens, we were unable to detect CD18. We suggest that expression of the
      CD11b/CD18 heterodimer might facilitate transmission of HIV by enhancing binding
      of HIV-antibody complexes in seminal fluid to epithelial cells. Alternatively,
      since intercellular adhesion molecule-1 (ICAM-1) is a receptor for CD11b/CD18,
      this may promote adhesion between epithelial cells and HIV-infected mononuclear
      cells in seminal fluid.

PMID- 7586698
TI  - Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the
      affected organs of sarcoidosis patients.
AB  - We investigated surface antigens and spontaneous cytokine production of T cells
      from bronchoalveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary
      sarcoidosis patients for a better understanding of the role of T cells in
      granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on
      freshly isolated T cells in the BALF of patients were significantly lower than
      those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or
      healthy donors (HD). In contrast, the levels of CD80 (B7/B7-1) and CD86 (B70/B7
      2) antigen expression were significantly higher on these T cells and alveolar
      macrophages in the BALF of patients. Fifty-three T cell clones (TCC) established
      from the BALF and AH of the three sarcoidosis patients displayed primarily either
      CD4+ CD11b+ CD28+ or CD4+ CD11b- CD28- phenotypes. Most (61-90%) of these TCC
      spontaneously produced greater amounts of IL-1 alpha, IL-10, tumour necrosis
      factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) than
      did TCC from the PBL from sarcoidosis patients or HD (P < 0.05). Interferon-gamma
      (IFN-gamma), IL-6, and IL-2, but not IL-4, were also produced by 40-48% of these
      TCC. These results suggest that CD4+ T cells of the affected organs of
      sarcoidosis patients are activated and involved in the immunopathogenesis of
      sarcoidosis through production of various cytokines.

PMID- 7586696
TI  - Dual action of IL-4 on mite antigen-induced IgE synthesis in lymphocytes from
      individuals with bronchial asthma.
AB  - Polyclonal IgE synthesis was efficiently induced by Dermatophagoides farinae (Df)
      antigen in freshly derived peripheral blood lymphocytes from mite-sensitive
      individuals with bronchial asthma. The in vitro IgE production was significantly
      correlated with total serum IgE values. The induced IgE synthesis was inhibited
      in a dose-dependent manner by antibodies to IL-4, indicating a role for
      endogenous IL-4. Although IL-4 alone increased IgE production, high
      concentrations (1-100 U/ml) of the cytokine inhibited Df antigen-stimulated
      production of IgE. However, low concentrations (0.001-0.01 U/ml) of IL-4
      significantly enhanced Df antigen-induced IgE production, as did high doses of IL
      4 when endogenous IL-4 was neutralized by antibodies to IL-4. Two other
      cytokines, IL-10 and interferon-gamma (IFN-gamma), showed contrasting actions, as
      judged from experiments with, exogenous cytokine and anti-cytokine antibodies: IL
      10 enhanced and IFN-gamma inhibited Df antigen-induced IgE synthesis. Thus, mite
      stimulated IgE production in lymphocytes from individuals with bronchial asthma
      appears to be regulated by at least three cytokines: IL-4, IL-10, and IFN-gamma.

PMID- 7586699
TI  - A possible role for lysozyme in determining acute exacerbation in chronic
      bronchitis.
AB  - The aggregation of non-serotypable Haemophilus influenzae (NTHI) by whole saliva
      from patients with chronic obstructive lung disease (COLD) was investigated.
      Significant differences were observed between salivary aggregating activity of a
      control and COLD population (P < 0.001). Saliva from patients less prone to acute
      exacerbations had a greater capacity to aggregate bacteria compared with saliva
      from patients with a predilection to infection. The mechanism of saliva-mediated
      aggregation of NTHI was investigated and shown to be related to lysozyme content.
      Lysozyme activity in saliva was measured by the turbidimetric technique and
      results showed that patients with chronic bronchitis had increased levels of
      salivary lysozyme, with a subpopulation within the non-infection-prone group
      having greater amounts. A significant difference was observed in salivary
      lysozyme between controls and non-infection-prone (P < 0.005) and infection-prone
      (P < 0.05) patients, respectively: the non-infection-prone patients having
      significantly (P < 0.005) more than the infection-prone patients. There was
      significant correlation (r = 0.742, P < 0.001) between salivary aggregation of
      NTHI and lysozyme activity. Chromatographically purified human lysozyme had a
      similar aggregation profile to that of saliva. There was no difference in serum
      and saliva lactoferrin concentrations between groups, but there was a significant
      increase (P < 0.05) in serum lysozyme concentration in the non-infection-prone
      group. This study suggests that the level of salivary lysozyme derived from
      macrophages may play an important role in determining resistance or
      susceptibility to acute bronchitis.

PMID- 7586697
TI  - Measurement of IL-4 in tears of patients with seasonal allergic conjunctivitis
      and vernal keratoconjunctivitis.
AB  - To elucidate the mechanism of ocular surface allergic disease, we focused on IL
      4, which is one of the key factors in regulating IgE production, and thus
      determined the concentration of IL-4 in tears. IL-4 concentration was determined
      in the tears of 15 patients with seasonal allergic conjunctivitis, 15 vernal
      keratoconjunctivitis (VKC), 10 giant papillary conjunctivitis (GPC), 10 patients
      with non-allergic conjunctivitis and post-cataract surgical conjunctivitis as
      intermediate conjunctivitis, and 10 normal subjects using a highly sensitive
      sandwich ELISA. The mean level of IL-4 in normal controls was low, and seasonal
      allergic conjunctivitis, VKC and GPC showed a significant elevation (P < 0.05),
      respectively. IL-4 of VKC and GPC were also significantly higher than allergic
      conjunctivitis, and non-allergic conjunctivitis and post-cataract surgical
      conjunctivitis were not higher than normal. These results raise the possibility
      that the increased level of IL-4 in tears could play a role in allergic disease
      and its severity in patients.

PMID- 7586700
TI  - Functional platelet-derived growth factor-beta (PDGF-beta) receptor expressed on
      early B-lineage precursor cells.
AB  - Growth and maturation of B lymphocytes from stem cells require a series of
      complex processes that are dependent at least in part on growth factors.
      Uncontrolled expression of receptors from these early growth factors may
      contribute to a leukaemogenesis of such early B cell progenitors. We show here
      that early pre-pre-B cells, but not mature B cells, express the PDGF receptor
      beta (PDGFR-beta). These receptors contain a protein tyrosine kinase domain which
      is activated upon ligation with PDGF in pre-pre-B cells. Further, pre-pre-B
      leukaemia cells seem to express more PDGFR-beta compared with their normal
      counterparts, suggesting a role for these receptors in growth promotion of
      leukaemia cells.

PMID- 7586701
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces
      toxoplasmastatic activity of human monocytes via induction of prostaglandin E2
      (PGE2).
AB  - In this study we investigated the effect of human GM-CSF on the toxoplasmastatic
      activity and release of H2O2 and PGE2 by human monocytes. Incubation of monocytes
      from healthy controls with GM-CSF resulted in a dose-dependent reduction of
      toxoplasmastatic activity and a decrease in H2O2 production. Furthermore GM-CSF
      treated monocytes released more PGE2 than untreated cells. To investigate the
      role of PGE2 in the reduced toxoplasmastatic activity of GM-CSF-treated
      monocytes, these cells were incubated with indomethacin. This resulted in a
      reduction of PGE2 release and restoration of toxoplasmastatic activity of
      monocytes treated with GM-CSF. GM-CSF reduces the toxoplasmastatic activity of
      monocytes via production of PGE2.

PMID- 7586704
TI  - Functions of the renin-angiotensin system during development.
AB  - 1. From studies in chronically catheterized fetal sheep and other species, it can
      be shown that the renin-angiotensin system (RAS) is active during intra-uterine
      life. Levels of angiotensin II (AII) in fetal sheep are similar to maternal. 2.
      The fetal RAS plays a role in maintenance of arterial pressure. The extent to
      which it does so depends on the level of activity of the system. 3. The
      distribution of renin within the fetal rat kidney is much more widespread than in
      the adult. The fetal kidney, like other vascular beds has high levels of the AT2
      angiotensin receptor subtype. With maturation the proportion of the AT1 receptor
      subtype increases. 4. Blockade of the fetal RAS with angiotensin converting
      enzyme (ACE) inhibitors or with the non-peptide AII antagonist (losartan) caused
      a fall in fetal glomerular filtration rate (GFR) and a rise in renal blood flow
      (RBF). AII reverses the fall in GFR even though RBF decreases. 5. The fraction of
      the filtered sodium load reabsorbed by the proximal tubule was not affected when
      the fetal RAS was blocked by captopril or losartan. High doses of infused AII had
      no effect on renal reabsorption of sodium, in the short term, but in the long
      term depressed fractional proximal reabsorption. 6. Only in high doses does AII
      stimulate the secretion of aldosterone from the fetal adrenal.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7586703
TI  - Peptide phage libraries can be an efficient tool for identifying antibody ligands
      for polyclonal antisera.
AB  - We have examined the potential of isolating ligands for polyclonal antibodies
      from a nanopeptide phage library. The library was screened with a rabbit
      polyclonal antiserum raised against a synthetic peptide (ALWFRNHFVFGGGTKVT).
      Following screening, the positive phages were tested in an ELISA for their
      reactivity with the antiserum. Phages that showed positive reactivity with the
      antiserum compared with a normal rabbit serum were selected and their displayed
      peptides were determined. Among the 36 random positive clones, 31 clones carried
      the sequence AVFGGGTKL, PFFGGGSRA or APTGGSKRT that have a significant homology
      to the immunizing peptide. Five positive phages displayed the ATNIFIEGT sequence,
      which has no obvious linear homology with either the other selected peptides or
      with the peptide used for immunization. In contrast to the control peptide, the
      immunizing peptide inhibited binding of the antiserum to the peptide-displaying
      phages in a dose-dependent manner, thus demonstrating the specificity of the
      interaction. Furthermore, the rabbit B cell response to the peptide was found to
      be limited and focused on its C-terminal. Taken together, our data demonstrate
      the potential of random peptide phage libraries for defining epitopes for
      polyclonal antisera as well as for investigation of the nature of B cell
      responses to any given antigen.

PMID- 7586705
TI  - Augmented endogenous nitric oxide production in partial portal vein-ligated rats.
AB  - 1. Endothelium-derived nitric oxide (NO) is a potent vasodilator. Because the
      body oxidizes it to nitrate ions, NO3-, measurement of the serum concentration
      and the urinary excretion of NO3- may be an index for endogenous NO. We
      investigated the role of NO on hyperdynamic circulation in cirrhotic and partial
      portal vein-ligated rats by measuring NO3. 2. Liver cirrhosis was induced by
      administration of thioacetamide. Systemic and splanchnic haemodynamics and
      splenic-systemic shunting were determined by tracer microspheres. The
      concentration of NO3- was measured by using high-performance liquid
      chromatography with an anioncolumn. 3. We found that systemic and splanchnic
      hyperdynamic circulation existed to almost the same extent in cirrhotic and in
      portal vein-ligated rats as compared to the controls and shamoperated rats,
      respectively. Splenic-systemic shunting was markedly greater in portal vein
      ligated rats than in cirrhotic rats. 4. Serum NO3- levels and urinary excretion
      of NO3- in cirrhotic rats tended to increase as compared to the controls. On the
      other hand, the levels in portal vein-ligated rats were significantly increased
      as compared to those of the shamoperated rats, and were significantly and
      negatively correlated to the splanchnic arterial resistance and total vascular
      resistance. The amount of urinary excretion of NO3- significantly correlated to
      splenic-systemic shunting (r = 0.61, P < 0.05) only in portal vein-ligated rats.
      5. We suggest that these high levels of NO3- in portal vein-ligated rats relate
      to the extensive formation of porto-collateral vasculature or acute changes in
      systemic and splanchnic haemodynamics due to portal vein-ligation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7586702
TI  - Lipopolysaccharide (LPS) down-regulates CD4 expression in primary human
      macrophages through induction of endogenous tumour necrosis factor (TNF) and IL-1
      beta.
AB  - The regulation of CD4 expression on macrophages and its role in immune cell
      interactions remain obscure. In contrast with primary lymphocytes, primary
      macrophages express only low amounts of surface CD4, which is regulated
      differentially for example by adherence in vitro. We report that addition of LPS
      for 1-5 days to human blood monocyte tissue culture-derived macrophages (TCDM)
      down-regulates both surface CD4 expression and total cellular CD4 antigen content
      as measured by flow cytometry and Western blot analysis. TNF-alpha and IL-1 beta,
      proinflammatory cytokines which are both induced by LPS, also down-regulate
      surface and total CD4 expression in TCDM. This down-regulation of CD4 expression
      by LPS, TNF-alpha, and IL-1 beta occurs at the level of transcription. The
      decreased macrophage CD4 expression induced by LPS was blocked by MoAbs directed
      against human TNF-alpha and IL-1 beta, demonstrating that LPS acts on CD4
      expression through induction of endogenous TNF-alpha and IL-1 beta. Conversely,
      neither LPS nor TNF-alpha and IL-1 beta were able to modulate surface CD4
      expression on quiescent or phytohaemagglutinin (PHA)-activated lymphocytes. Of
      other cytokines and growth factors tested, Th2 cytokines (IL-4, IL-10, IL-13),
      chemokines (MCP-1, MIP-1 alpha, RANTES), and macrophage colony-stimulating factor
      did not alter CD4 expression in primary macrophages; granulocyte-monocyte colony
      stimulating factor and the prototypal Th1 cytokine interferon-gamma (IFN-gamma)
      modulated surface CD4 expression only after prolonged treatment (5 days). Our
      results show that LPS, TNF-alpha and IL-1 beta selectively down-regulate CD4
      expression in primary human macrophages, and that decreased CD4 expression
      induced by LPS results from endogenous secretion of TNF-alpha and IL-1 beta by
      the macrophages.

PMID- 7586706
TI  - Effect of renal nerve denervation on tissue catecholamine content in
      spontaneously hypertensive rats.
AB  - 1. To clarify the possible role of tissue catecholamines in the development of
      hypertension, we investigated the effect of bilateral renal denervation on the
      catecholamine contents of central and peripheral tissues in spontaneously
      hypertensive rats (SHR). 2. Norepinephrine (NE) content in renal cortex, renal
      medulla, and adrenal gland was higher in 7 week old SHR than age-matched Wistar
      Kyoto rats (WKY). Dopamine (DA) content in the brainstem and hypothalamus was
      also higher in SHR, but NE and epinephrine (EPI) content in these areas were not
      different between strains. Similar differences in catecholamines were observed in
      9 week old rats in which a sham operation of bilateral renal denervation was
      performed 2 weeks previously. 3. Bilateral renal denervation produced an almost
      complete reduction of NE content in the kidney in both strains and prevented the
      development of hypertension. DA content in the brainstem was also decreased by
      renal denervation in SHR but not in WKY. NE and EPI content in central tissues
      were not affected by renal denervation. 4. These results suggest that DA content
      in brainstem area, as well as NE content in the kidney, have a relationship in
      the development of hypertension in SHR.

PMID- 7586707
TI  - Repair and recovery following spinal cord injury in a neonatal marsupial
      (Monodelphis domestica).
AB  - 1. Repair and recovery following spinal cord injury (complete spinal cord crush)
      has been studied in vitro in neonatal opossum (Monodelphis domestica), fetal rat
      and in vivo in neonatal opossum. 2. Crush injury of the cultured spinal cord of
      isolated entire central nervous system (CNS) of neonatal opossum (P4-10) or fetal
      rats (E15-E16) was followed by profuse growth of fibres and recovery of
      conduction of impulses through the crush. Previous studies of injured immature
      mammalian spinal cord have described fibre growth occurring only around the
      lesion, unless implanted with fetal CNS. 3. The period during which successful
      growth occurred in response to a crush is developmentally regulated. No such
      growth was obtained after P12 in spinal cords crushed in vitro at the level of C7
      8. 4. In vivo, in the neonatal (P4-8) marsupial opossum, growth of fibres
      through, and restoration of, impulse conduction across the crush was apparent 1-2
      weeks after injury. With longer periods of time after crushing a considerable
      degree of normal locomotor function developed. 5. By the time the operated
      animals reached adulthood, the morphological structure of the spinal cord, both
      in the region of the crush and on either side of the site of the lesion, appeared
      grossly normal. 6. The results are discussed in relation to the eventual longterm
      possibility of devising effective treatments for patients with spinal cord
      injuries.

PMID- 7586708
TI  - Influence of body temperature on responses to hypoxia and hypercapnia:
      implications for SIDS.
AB  - 1. This paper reviews current knowledge regarding interactions between body
      temperature and the respiratory responses to hypoxia and/or hypercapnia, with
      special emphasis on how these interactions might predispose towards sudden infant
      death syndrome (SIDS). 2. Use has been made of an adult rat model in which body
      core temperature is fixed by means of an intra-abdominal heat exchanger. Initial
      studies indicated that hyperthermia (Tb approximately 41 degrees C) enhanced the
      ventilatory response to hypercapnia, whereas hypothermia (Tb approximately 35
      degrees C) interacted with hypoxia to depress respiration. 3. Studies involving
      hypothalamic lesions in urethane-anaesthetized rats have implicated the posterior
      hypothalamic area in the hypoxia/hypothermia interaction. Further studies are
      directed towards examining the role played by more caudal areas, including the
      raphe nuclei. 4. It has been shown that not only does the hypoxia/hypothermia
      interaction depress breathing but it also reduces, or sometimes eliminates, the
      ventilatory response to hypercapnia, which under normal circumstances provides
      one of the most powerful excitatory inputs to the respiratory centres. This
      implies that an expected reversal of the respiratory depression by build up of
      CO2 levels may not occur, which in turn has important implications for SIDS. 5.
      The literature dealing with the effects of hyperthermia on hypoxic and
      hypercapnic responses is also reviewed. It is concluded that environmental heat
      stress may only become a significant problem when it accompanies a febrile
      infection, under which circumstances it may seriously compromise thermoregulatory
      ability and alter breathing responses to chemical stimuli.

PMID- 7586709
TI  - Hypoxic inhibition of breathing and motor activity in the foetus and newborn.
AB  - In fetal animals hypoxia of rapid onset causes cessation of breathing movements,
      electro-ocular activity and decrease of muscle tone. These effects last several
      hours and are in contrast to the hypernoea and behavioural activation which
      occurs during hypoxia soon after birth and in the adult. Transection and lesion
      studies in fetal sheep suggest that hypoxia activates a descending inhibition of
      respiratory and other motor activities which either originates in the pons or is
      conveyed to medullary and spinal levels of the neuraxis by fibres through the
      pons in the region of the Kolliker-Fuse nucleus. Recently, using FOS
      immunohistochemistry we have identified cells in the medial parabrachial complex
      which are activated by hypoxia in fetal sheep, but not newborn lambs. It is
      proposed that these cells have descending inhibitory connections with respiratory
      and spinal motor pathways, but the precise anatomy and neurochemistry of such
      pathways is unknown. It is not known if the parabrachial cells are directly
      sensitive to low Po2 or receive input from other centres or peripheral receptors
      which monitor arterial Po2 in the foetus. Nor is it known why these cells are not
      activated by low Po2 after birth.

PMID- 7586710
TI  - Postnatal development of responses to airflow obstruction.
AB  - 1. Obstruction of the upper airway could be an initiating factor in the Sudden
      Infant Death Syndrome (SIDS). Responses to upper airway obstruction include
      augmentation of respiratory efforts, active dilation of the upper airway and
      electrocortical arousal. Vulnerable individuals may fail to mount these responses
      effectively. 2. Respiratory and arousal responses to obstruction of the upper
      airway have been investigated in newborn lambs. In conscious lambs, nasal
      obstruction causes a profound augmentation of inspiratory efforts, mild
      asphyxiation and eventual formation of an oral airway. The ability to establish
      an oral airway involves both chemoreception and mechanoreception and improves
      with age. 3. In sleeping lambs, obstruction of tidal airflow leads to progressive
      hypoxaemia, augmentation of inspiratory efforts, bradycardia and arousal. Arousal
      occurs earlier and with less hypoxaemia and bradycardia in non-REM sleep than in
      REM sleep. Arousal occurs after inspiratory efforts have increased to the same
      extent during both sleep states, suggesting that mechanoreception, or a sense of
      inspiratory effort, is important in initiating arousal. 4. Obstruction of nasal
      tubes tends to cause arousal from sleep earlier, and with less hypoxaemia and
      less augmentation of inspiratory effort, than when a more compliant face mask is
      obstructed. This supports the suggestion that mechanoreception, which may be
      involved in the perception of inspiratory effort, is a determinant of arousal. 5.
      With increasing postnatal age, lambs become less arousable in response to airflow
      obstruction when in REM sleep. This suggests that lambs may become progressively
      more vulnerable to the effects of airway obstruction during the immediate newborn
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586711
TI  - Physiological studies of gastro-oesophageal reflux and airway protective
      responses in the young animal and human infant.
AB  - 1. The mechanisms that underlie the Sudden Infant Death Syndrome (SIDS) must
      explain its two unique features; age at death and death during apparent sleep. 2.
      The occurrence of gastro-oesophageal reflux (GOR) during active sleep in infants
      presenting with apparent life threatening episodes (ALTE) and their similar age
      distribution to SIDS infants, suggested that reflux could be a cause of asphyxia.
      3. Sleep related GOR was found to be a physiological and not a pathological event
      in normal, healthy term infants. 4. In healthy term infants, those infants that
      were formula-fed (who have a higher incidence of SIDS) had significantly longer
      oesophageal clearance times for acid reflux and significantly more active sleep
      compared with breast fed infants. 5. In very preterm infants (who are at
      increased risk for SIDS), both the frequency and duration of reflux during active
      sleep was significantly less at term equivalent age compared with healthy term
      infants, suggesting additional factors must operate to promote an ALTE. 6. One
      mechanism which may explain the pathogenesis of GOR could be that the reflux
      reaches the level of the pharynx and this, in turn, stimulates laryngeal
      receptors to produce apnoea. 7. Simulated reflux to the level of the pharynx in
      the sleeping piglet evoked airway protective responses, namely swallow, arousal
      and occasionally expectoration, but neither apnoea nor oxygen desaturation. 8. In
      the same piglets treated with pentobarbitone sodium, swallowing was impaired and
      arousal depressed. Simulated reflux to the pharynx produced significant apnoea
      and oxygen desaturation and death in two of five piglets.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7586712
TI  - Wiring up the visual system.
AB  - 1. In this review we describe some of our recent studies on the developing
      marsupial visual pathway. The description focuses on retinal ganglion cells,
      considering the formation of their dendritic trees, the outgrowth of axons and
      the formation of connections within the brain. 2. Both dendritic trees and
      outgrowing axons undergo a period of exuberance, followed by one of refinement.
      The dendritic tree transiently develops a more complex branching pattern than is
      found in adults. Short side branches, referred to as spines, are a feature of
      immature dendrites and, to a lesser extent, of axons. These structures are mostly
      lost as development proceeds. However, they are retained on the dendritic trees
      of small-field ganglion cells and, for a proportion of axons, on that part within
      the nerve fibre layer of the retina. Although most axons navigate fairly direct
      routes towards their targets, a minority follow inappropriate courses, such as
      doubling back towards the eye or entering the opposite optic nerve at the chiasm.
      As such errant axons are not seen in the adult, we assume that their parent cell
      bodies die during development. 3. Throughout development, optic axons are
      arranged in an approximate retinotopic order along the length of the visual
      pathway; as a result, axons approach the visual centres aligned to form, at
      least, a crude retinotopic map. Axons from dorsal and ventral retina exchange
      locations along the optic nerve and in this way correct for the inversion of the
      image brought about by the lens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586714
TI  - Developmental signalling.
AB  - 1. In investigating the communication paths between target tissue and neurons we
      have been led to propose two classes of neurotrophic factors. One comprises the
      factors which transport themselves, the other factors relying on the transport of
      a second messenger. The former may have labile second messenger systems
      necessitating the translocation of agonist and receptor from the nerve terminal
      to the cell body and the latter must possess a stable second messenger system
      that itself is sufficiently robust to survive the transport to the cell body. 2.
      One such class of stable messengers may be the GTP-binding protein family and it
      has been shown that the alpha subunits of both Gi alpha and Gz alpha can be
      retrogradely transported in the mouse sciatic nerve. 3. Examination of the cell
      bodies in the dorsal root ganglia revealed that Gz alpha accumulated in the
      nucleus of cells with intact axons but that 24 h after axonal ligation this
      immunoreactivity decreased. 4. It is suggested that Gz is activated at the nerve
      terminal and it, or at least its alpha subunit, undergoes retrograde transport to
      the cell body where it accumulates in the nucleus.

PMID- 7586713
TI  - Regulation of neural precursor differentiation in the embryonic and adult
      forebrain.
AB  - 1. Precursors form the neuroepithelium of the developing cortex and also from the
      adult sub-ventricular zone, can be cloned in vitro after stimulation with
      fibroblast growth factor (FGF)-2 and have the potential to give rise to both
      neurons and glia. The generation of neurons from these clones can be stimulated
      by either a factor derived from an astrocyteprecursor line, Ast-1, or FGF-1. 2.
      Neuronal differentiation stimulated by FGF-1 can be inhibited by diacylglycerol
      lipase inhibitor and mimicked by arachidonic acid, suggesting that the neuronal
      differentiation is signalled through the PCL gamma pathway. 3. The sequential
      expression of FGF-2 and FGF-1 within the developing forebrain neuroepithelium
      fits with the different functions the two FGF play in precursor regulation. 4. We
      have shown that the precursor response to FGF-1 is regulated by a heparan
      sulphate proteoglycan (HSPG) expressed within the developing neuroepithelium.
      Precursors restricted to the astrocyte cell lineage can be stimulated by
      epidermal growth factor or FGF-2; however, the differentiation into GFAP positive
      astrocytes appears to require a cytokine acting through the leukaemia inhibitory
      factor beta receptor.

PMID- 7586715
TI  - Schwann cells and the regrowth of axons in the mammalian CNS: a review of
      transplantation studies in the rat visual system.
AB  - 1. We have used peripheral nerve transplants or cultured Schwann cells grafted in
      association with different types of polymer to study axonal regrowth in the rat
      visual system. In some instances the glia were co-grafted with fetal tectal
      tissue. 2. The studies have two main aims: (i) to determine whether retinal axons
      can be induced to regrow at a site distant from their cell soma, that is, after
      damage to the brachial region of the optic tract; (ii) to determine whether
      retinal axons exposed to Schwann cells retain the ability to recognize their
      appropriate target neurons in CNS tissue. 3. In brachial lesion studies, Schwann
      cells were placed in the lesion site in association with nitrocellulose papers,
      within polycarbonate tubes in the presence or absence of a supporting
      extracellular matrix (ECM), or within polymer hydrogel scaffolds. Autologous
      sciatic nerve grafts were also used. Immunohistochemical studies revealed the
      presence of regenerating axons within all polymer bridges. Regrowth of retinal
      axons was also seen, however, growth was not extensive and was limited to the
      proximal 1-1.5 mm of the implants. 4. In target innervation experiments, two
      surgical paradigms were developed. In one experiment, a segment of sciatic nerve
      was autografted onto the transected optic nerve in adult rats and the distal end
      of each graft was placed adjacent to fetal tectal (target) tissue implanted into
      the frontal cortex. To date, we have not been able to demonstrate selective
      recognition of target regions within tectal transplants by retinal axons exiting
      the sciatic nerve implants. 5. In the second experiment, Schwann cells were mixed
      with fetal tectal cells and co-grafted to the midbrain of newborn host rats.
      Schwann cells altered the characteristic pattern of host retinal growth into
      tectal grafts; in some cases axons were induced to grow away from appropriate
      target areas by nearby co-grafted Schwann cells. 6. In summary, Schwann
      cell/polymer scaffolds may provide a useful way of promoting the regrowth of
      damaged axons in the CNS, however: (i) in adults, at least, their effectiveness
      is reduced if they are located at a distance from the cell bodies giving rise to
      regenerating axons; (ii) in some circumstances exposure to a peripheral glial
      environment may affect the capacity of regenerating axons to recognize
      appropriate target cells in the CNS neuropil.

PMID- 7586716
TI  - Effects of lifestyle, coping and work-related stress on blood pressure in office
      workers.
AB  - 1. The relative importance of perceived stress compared with coping behaviours
      and 'lifestyle' characteristics known to influence blood pressure were studied in
      337 male and 317 female office workers. 2. Males had significantly higher mean
      systolic (P < 0.01; t-test, 652 d.f.) and diastolic (P < 0.01; t-test, 652 d.f.)
      blood pressure and unhealthier lifestyles than females, particularly in the areas
      of alcohol intake (P < 0.01; t-test, 653 d.f.) and diet (P = 0.01; t-test, 663
      d.f.) 3. In males drinking alcohol was correlated to job and home/work stress (P
      < 0.05), and eating more atherogenic foods was correlated to home/work stress (P
      < 0.05). 4. Coping by food and drug consumption was correlated with job and
      home/work stress (P < 0.05) in males; avoidance/denial coping was correlated with
      job stress in both males and females (P < 0.001) and to home/work stress (P <
      0.001) in males only. Blood pressure was not correlated with stress in males or
      females. 5. In age-adjusted regression analyses body mass index (BMI) and
      lifestyle (physical inactivity, alcohol consumption and diet) made significant
      contributions to systolic (P = 0.02) and diastolic (P < 0.01) blood pressure and,
      in separate analyses, coping contributed significantly to diastolic blood
      pressure (P < 0.01) in males. Stress made no additional contribution to blood
      pressure in either analysis. 6. After including age, BMI, lifestyle and coping in
      males 'lifestyle' still contributed to systolic and diastolic blood pressure and
      coping made a significant additional contribution to diastolic blood
      pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586717
TI  - Effects of sodium depletion on tissue concentrations of the natriuretic hormone
      vasoactive intestinal peptide.
AB  - 1. Variations in dietary sodium intake have been shown to affect the plasma
      concentration, the metabolic clearance rate and secretion rate of vasoactive
      intestinal peptide (VIP). In this study we sought to determine the effect of
      sodium depletion on the concentration of VIP in plasma and in three tissues,
      namely heart, lung and kidney. 2. Male Sprague-Dawley rats were placed on low or
      normal sodium diets and drinking water ad libitum. A third group was placed on a
      low salt diet and in addition were given frusemide, 1mg/kg per day in the
      drinking water. After 7 days the rats were killed, a blood sample collected and
      tissues harvested. VIP concentrations were determined by radioimmunoassay on
      unextracted plasma and in tissue after extraction. 3. There were significant
      differences between the three groups in the concentration of VIP in the lung (P <
      0.0005), kidney (P < 0.005) and plasma (P < 0.025) but not the heart. In the
      group that received frusemide and the low sodium diet, VIP in the lung was
      significantly lower than the low sodium (P < 0.005) and normal sodium (P <
      0.0001) groups. Similar differences were noted in the kidney (frusemide vs low
      sodium, P < 0.001; frusemide vs normal, P < 0.01) and plasma (frusemide vs low
      sodium P < 0.001, frusemide vs normal P < 0.05). 4. We conclude that sodium
      depletion decreases the concentration of VIP in plasma and in its metabolizing
      tissues.

PMID- 7586718
TI  - Superantigens in Kawasaki syndrome.
AB  - Kawasaki syndrome (KS) is an acute multisystem vasculitis of infancy and early
      childhood associated with the development of myocarditis and coronary artery
      abnormalities. Despite the widely held belief that KS is caused by an infectious
      agent, there remains considerable controversy over its etiology. Recent
      immunologic and microbiologic studies suggest a potential role for staphylococcal
      and streptococcal toxins (superantigens) in the pathogenesis of KS. Confirmation
      of these findings could result in more effective diagnostic and therapeutic
      approaches to this common cause of acquired heart disease in children.

PMID- 7586720
TI  - High correlations of anti-CMV titers with lymphocyte activation status and CD57
      antibody-binding capacity as estimated with three-color, quantitative flow
      cytometry in blood donors.
AB  - Blood samples of 58 blood donors (ages 19-64 years, 31 males and 27 females) were
      investigated with three-color, quantitative flow cytometry. IgG anti
      cytomegalovirus (CMV) was estimated with ELISA. Nineteen men and 21 women were
      found CMV-seropositive. The seropositive individuals (CMV-pos) compared to the
      seronegative ones (CMV-neg) presented no significant changes in the absolute
      number of lymphocytes or in the main lymphocyte subpopulations identified by
      CD20, CD3, CD4, and CD8. Nevertheless, CMV-pos showed significantly higher
      numbers of lymphocytes with the following phenotypes: CD4+HLA-DR+, CD8+HLA-DR+,
      CD8+CD45RA+ CD45RO+, and CD20+CD5+. The CD3+CD57+ subset of T lymphocytes was
      also significantly higher in CMV-pos (P < 0.0001), whereas the CD57+CD16 &
      CD56+CD3- NKC subset presented similar values in both groups. Higher values for
      the antibody-binding capacity of lymphocytes CD38 (P < 0.05) and CD45 (P = 0.02)
      antigens and of CD57 antigen on CD3+ lymphocytes (P < 0.0005) were found in the
      CMV-pos group. These results show that CMV upregulates the number of CD57
      molecules on CD3+ and not on CD3- lymphocytes and suggest that the CD3 molecule
      or other molecules specifically present in T cells can play a role in CMV
      latency. The study also showed that CMV plays a major role in the maintenance of
      a fraction of lymphocyte in the activated state.

PMID- 7586719
TI  - Anti-GOR and anti-thyroid autoantibodies in patients with chronic hepatitis C.
AB  - Anti-thyroid autoantibodies have been described in anti-hepatitis C virus (HCV)
      positive patients. It has been suggested that the anti-GOR response is closely
      related to HCV infection and may reflect an HCV-associated autoimmune phenomenon.
      This study was designed to evaluate the humoral anti-GOR response in anti-HCV
      positive patients with anti-thyroid autoantibodies (group 1, 22 patients) and to
      compare it with the response in anti-HCV-positive patients without anti-thyroid
      autoantibodies (group 2, 44 patients) and in anti-HCV-negative patients with
      autoimmune thyroiditis (group 3, 28 patients). The prevalences of anti-GOR in
      groups 1, 2, and 3 were, respectively, 72.7, 61.3, and 3.5%. Anti-GOR levels were
      higher in group 1 than in group 2 or group 3 (P = 0.0001). Moreover, comparison
      of the Anti-GOR levels of groups 1 and 2 also revealed a statistically
      significant difference (P = 0.008). Detection of more elevated anti-GOR levels in
      group 1 patients suggests that anti-thyroid autoantibodies in anti-HCV-positive
      patients may be related to HCV.

PMID- 7586721
TI  - Allogenic BMT in children: differential lymphocyte subset reconstitution
      according to the occurrence of acute GVHD.
AB  - To acquire some biological markers associated with the occurrence of acute graft
      versus-host disease (aGVHD) after allogeneic bone marrow transplant (BMT) in
      children, we have studied the lymphocyte subset reconstitution and the percentage
      of peripheral blood mononuclear cells bearing HLA-DR and HLA-DQ class II
      molecules. This study included 37 allogeneic BMT: either with (n = 17) or without
      (n = 20) aGVHD. Within 2 months after transplantation, we observed that patients
      with aGVHD had a unique mononuclear cell profile characterized by (i) a
      significant increase in the percentages of CD8bright+CD28- T cells (P = 0.05) and
      CD3+ T cells (P = 0.001), (ii) an important decrease in the percentage of CD56+
      cells (P = 0.0001), and (iii) a decrease in the percentages of HLA-DQ+ and HLA
      DR+ monocytes (P = 0.001) and HLA-DQ+ T lymphocytes (P = 0.0001), in comparison
      with patients without aGVHD. Moreover, statistical studies indicate that there
      was a positive correlation between CD8bright+CD28- and CD3+ T cells, whereas CD3+
      T cells were negatively correlated to CD56+ cells. We did not find any
      statistical correlation between the percentages of HLA-DQ+ or HLA-DR+ cells and
      the percentages of these lymphocyte subsets. Therefore, in this study done in
      children, we suggest that patients with (i) less than 20% of DQ+ monocytes, (ii)
      less than 25% of CD56+ lymphocytes, and (iii) an enhanced percentage of
      CD8bright+CD28- T cells are strongly associated with aGVHD. Unfortunately, these
      biological markers of a GVHD may not precede the clinical manifestations of the
      disease.

PMID- 7586722
TI  - Characterization of a novel human antibody xenoreactive with fibronectin.
AB  - Recent reports have used bovine fibronectin (Fn) as source of antigen to study
      human anti-Fn autoantibodies. We have characterized a novel human antibody (Ab)
      reactive with bovine and marsupial Fn, but not with human Fn. Indirect
      immunofluorescence, wet cleaving and protein adherence assays, immunoblotting,
      blot-affinity purification, a cell adhesion inhibition assay, and competitive
      experiments with synthetic peptides were used to characterize the anti-Fn Ab in
      serum from a patient with an undifferentiated connective tissue disease. A
      characteristic Fn-like network was observed by indirect immunofluorescence on
      bovine MDBK and marsupial PtK2 cells, but not on various human cell lines. Double
      immunofluorescence revealed colocalization of the Ab with a mouse monoclonal anti
      Fn Ab. A reactive polypeptide of 240 kDa corresponding to the M(r) of Fn was
      identified by immunoblotting using MDBK and PtK2 total cell lysates. The Ab
      reacted with the 240-kDa band of purified bovine Fn with an endpoint titer of
      1:64,000, while no reactivity was observed with human cellular or plasma Fn. Blot
      affinity purification of the Ab from the 240-kDa PtK2 region confirmed that the
      Fn-like fluorescent pattern observed was due to reactivity with the 240-kDa band
      and not with other regions of the blot. The Ab affinity-purified from the 240-kDa
      region also reacted with purified bovine Fn by immunoblotting. Functional
      analysis disclosed specific inhibition of PtK2 and MDBK cell adhesion by the
      affinity-purified anti-Fn Ab. Competitive experiments with synthetic peptides
      demonstrated that the epitope is located in the decapeptide RGDSPASSKP containing
      the cell-binding domain of Fn. Longitudinal analysis of the Ab revealed its
      persistence over 6 years. Bovine and marsupial Fn can be the focus of a highly
      specific and persistent human immune response. Reactivity of a human Ab with
      bovine Fn does not imply cross-reactivity with human Fn. In light of recent
      reports using bovine Fn to characterize human anti-Fn "autoantibodies," future
      studies on human anti-Fn should specifically employ purified human Fn as antigen.

PMID- 7586724
TI  - Lymphocyte subsets and plasma IL-1 alpha, IL-2, and TNF-alpha concentrations in
      acute rheumatic fever and chronic rheumatic heart disease.
AB  - The distribution of CD3+, CD4+, CD8+, CD19+, CD16+, and CD25+ lymphocyte
      populations in peripheral blood as well as the plasma concentrations of
      interleukin-1 alpha (IL-1 alpha), and IL-2 and tumor necrosis factor alpha (TNF
      alpha) were investigated in 25 children with acute rheumatic fever (ARF) at the
      time of admission and after 3 months and in 15 children with chronic rheumatic
      heart disease (CRHD) and in 15 children with streptoccocal pharyngitis (SP) in
      order to determine changes in lymphocyte subsets and cytokine concentrations
      occurring during different stages of the disease. The percentages and absolute
      counts of CD4+, CD16+, CD25+ cells, the ration of CD4/CD8 and plasma
      concentrations of IL-1 alpha and IL-2 in patients with ARF were significantly
      higher at admission than 3 months later. These levels were also significantly
      higher than in patients with CRHD, SP, or normal controls. Production of IL-2 in
      ARF and CRHD patients directly correlated with the percentages of CD4+ and CD25+
      cells. According to our results, the evidences of increased cellular immune
      response in ARF are increased percentages CD4+ and CD25+ cells, CD4/CD8 ratio,
      and increased plasma concentrations of IL-1 alpha and IL-2. Furthermore,
      activation of cellular immune response was not present throughout all stages of
      rheumatic heart disease and also in SP.

PMID- 7586723
TI  - Production of inflammatory cytokines by Epstein-Barr virus (EBV)-infected
      lymphoblastoid cell lines spontaneously originated from the peripheral blood of
      patients with human immunodeficiency virus (HIV) infection.
AB  - In this study we have raised spontaneous Epstein-Barr virus (EBV)-positive
      lymphoblastoid cell lines (LCL) from the peripheral blood of human
      immunodeficiency virus (HIV)-infected individuals and of control patients with
      primary EBV infections. These LCLs were also raised in the presence of the viral
      inhibitor phosphonoformate (PFA); under these conditions, the in vitro infection
      of bystander B lymphocytes with EBV released in culture by in vivo infected B
      cells is inhibited. Thus, the latter LCLs are likely to represent the progeny of
      B cells latently infected by EBV in vivo. The LCLs raised in the presence or
      absence of PFA had the same phenotypic features, type of EBV latency, and growth
      pattern irrespective of whether they had been raised from HIV-seropositive
      individuals or patients with primary EBV infections or had been generated by
      infecting normal B cells in vitro. Studies on the production of inflammatory
      cytokines were conducted by Northern blotting or by determining the cytokine
      concentrations in the cell supernatants by immunoassays or bioassays. Three of
      eight LCLs from HIV-seropositive patients released TNF alpha and 5/5 released TNF
      beta, IL6 was present in the supernatants of 1/8 LCLs, and IL1 alpha and IL1 beta
      were not detected in any culture supernatant. No differences were noticed in the
      patterns of cytokine secretion among the LCLs from HIV-seropositive patients and
      in those raised from patients with primary EBV infections or obtained by
      infecting normal B cells in vitro with EBV. It is tempting to speculate that
      abnormally expanded EBV-harboring B cells in HIV-seropositive patients may
      participate in the pathogenesis of certain clinical manifestations by releasing
      inflammatory cytokines; some of these cytokines might also contribute to the in
      vivo spreading of HIV infection. However, the spontaneous LCLs from HIV
      seropositive individuals do not display abnormal features compared to latently
      EBV-infected LCLs from other sources despite the high frequency of EBV-driven
      lymphoproliferative disorders observed in AIDS patients.

PMID- 7586726
TI  - Family and linkage study of selective IgA deficiency and common variable
      immunodeficiency.
AB  - Screening of close relatives of Swedish patients with selective immunoglobulin A
      deficiency (IgAD) and common variable immunodeficiency (CVID) for serum
      immunoglobulin levels has identified the positive family history of IgAD/CVID as
      the most significant risk factor for developing the disease. The relative risk
      for siblings of patients with IgAD was estimated to be approximately 50. In 12 of
      34 Swedish multiplex families identified in the study, both IgAD and CVID
      occurred, usually CVID in the parental generation and IgAD in the subsequent
      generation. This proportion was much higher than expected by chance and strongly
      suggests that the two clinically discernible disorders represent an allelic
      condition, reflecting a variable expressivity of a common defect. In 27 multiplex
      families the disorders segregated as an autosomal dominant trait, affecting at
      least two generations. A high relative risk for siblings, permanent phenotype,
      low number of phenocopies, and common population prevalence, which makes it
      possible to obtain a sufficient sample size, make these immunoglobin deficiencies
      amenable to genetic linkage analysis. In a pilot multicenter linkage study
      involving 16 multiplex families with dominant transmission of IgAD/CVID, we have
      attempted to confirm previously reported genetic linkage of the disease
      susceptibility to the major histocompatibility complex (MHC) region. Using both
      parametric and nonparametric linkage analyses with a set of microsatellite
      markers at and flanking the MHC region, no evidence for linkage was found. In
      accordance with these results, no evidence for linkage to the MHC region was
      obtained by analyzing previously published segregation data at the MHC region in
      multiplex families with IgAD/CVID in more than one generation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7586727
TI  - Identification of antigenic epitopes of 1D antigen recognized by antibodies in
      the serum of patients with thyroid-associated ophthalmopathy.
AB  - Random fragments of full-length 1D cDNA encoding the 64-kDa antigen were cloned
      and expressed in Escherichia coli as fusion proteins. Antigenic peptides were
      detected by colony blotting with sera from patients with thyroid-associated
      ophthalmopathy (TAO) and corresponding cDNA inserts were sequenced. Four
      antigenic peptides were characterized and positioned with respect to the 1D amino
      acid sequence. One antigenic peptide (G-8) was found to be close to the C
      terminal end of 1D, and three others (G-2, G-4, and G-5) were clustered at sites
      between amino acids 76 and 205. The immunoreactivities of a panel of sera were
      tested against full-length 1D and the four peptides. A panel consisting of sera
      from (1) 15 patients with TAO, (2) 9 patients with Graves' hyperthyroidism
      without ophthalmopathy, (3) 6 patients with Hashimoto's thyroiditis without
      ophthalmopathy, and (4) 12 normal subjects were tested against the four peptides
      and full-length 1D protein by Western blotting. Sera from patients with TAO also
      reacted more often with G-4 and/or G-5 peptides than did those from normal
      subjects [7 of 15 (47%) sera from TAO patients versus 1 of 12 (8%) sera from
      normal subjects; P < 0.05]. Based on positioning of peptides onto the full-length
      1D sequence and the reaction pattern of the serum panel, six immunogenic epitopes
      were identified on the 1D molecule.

PMID- 7586728
TI  - Regulation of human alveolar macrophage inflammatory cytokines by tyloxapol: a
      component of the synthetic surfactant Exosurf.
AB  - We previously demonstrated that the synthetic surfactant Exosurf and a modified
      natural surfactant, Survanta, both down-regulated endotoxin-stimulated production
      of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta,
      interleukin-6) in human alveolar macrophages. To further characterize the source
      of the inhibitory effect of surfactant, the three individual components of
      Exosurf were evaluated. Dipalmitoylphosphatidylcholine had no effect on endotoxin
      stimulated cytokine secretion. Cetyl alcohol (spreading agent) compromised
      macrophage function as measured by adherence. However, at concentrations
      equivalent to those found in the complete surfactant (Exosurf) preparation,
      tyloxapol (nonionic dispersing agent) was inhibitory in a dose-dependent manner.
      The viability of alveolar macrophages as assessed by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide cleavage assay was not affected by incubation in
      Exosurf or any of its individual components. Cytokine secretion and mRNA levels
      of endotoxin-stimulated alveolar macrophages were decreased by tyloxapol. These
      data suggest that tyloxapol alone, like Exosurf, has an inhibitory effect on
      cytokine production which may be pretranslationally mediated.

PMID- 7586725
TI  - Activation of human tonsil lymphocytes by rabies virus nucleocapsid superantigen.
AB  - The capacity of the rabies virus superantigen (SAg) and the nucleocapsid (NC) to
      activate human tonsil lymphocytes was analyzed by studying the capacity of NC to
      cause lymphocytes to proliferate and secrete Ig and cytokines. NC activation was
      compared to that obtained with the Staphylococcus-derived SAg, SEE, and TSST-1.
      Despite a weak T lymphocyte mitogenic activity restricted to CD4+ T cells, NC
      triggers tonsil B lymphocytes to produce IgG in quantities and frequencies
      similar to those of SEE and TSST-1. In the same way as these two SAg, NC induces
      IgG production only in the presence of T cells and optimally with a T/B ratio of
      1/5. However, unlike SEE and TSST-1, NC does not trigger IgM production. The
      pattern of cytokines produced upon NC activation, IL-4 and IL-10, weak IL-2
      production, and no IFN-gamma, suggests that rabies SAg stimulates Th2 rather than
      Th1 lymphocytes. In contrast, the pattern of cytokines produced upon TSST-1
      activation, IL-2, IFN-gamma, and no IL-4, suggests that TSST-1 induces rather a
      Th1 response. The specific Th2 triggering by NC could explain the unique capacity
      of the rabies SAg to increase the in vivo antibody response to a simultaneously
      injected antigen.

PMID- 7586729
TI  - HBV antigens in peripheral blood mononuclear cells (PBMC) during the course of
      viral infection.

PMID- 7586730
TI  - Lupus: key pathogenic mechanisms and contributing factors.
AB  - The past 30 years of research on murine and human systemic lupus erythematosus
      has served to identify an array of immunological aberrations--some shared, some
      unique, some primary, others secondary-- that may underlie this disease. In
      integrating these findings, it appears that at least four distinct pathogenic
      events characterize lupus: (1) Anti-DNA Abs and immune complexes induce renal
      damage; (2) B-cells produce pathogenic anti-DNA antibodies; (3) Th cells drive
      lupus B-cells; and (4) Increased concentrations and abnormal presentation of
      nucleosomes. The purpose of this review is to examine the roles of these four
      events in the pathogenesis of lupus and to identify the different factors that
      can precipitate these pathogenic events.

PMID- 7586731
TI  - Direct inhibition of human CD8+ lymphocyte activation by cyclosporine A and
      Rapamune-Sirolimus.
AB  - Cyclosporin A (CsA) and Rapamune-Sirolimus (RAP) have been shown to inhibit the
      in vitro activation of heterogeneous lymphocytes populations, but little is known
      about their direct actions on isolated CD8+ lymphocytes. In this study the direct
      effects of RAP and CsA on a highly purified population of CD8+ lymphocytes were
      examined. Human CD8+ lymphocytes were purified to near homogeneity and stimulated
      with anti-CD3 antibody, OKT3, or allogeneic cells in the presence of exogenous
      human recombinant interleukin 2 (IL2). The effects of CsA and RAP on cell
      proliferation, the entry into the S phase of the cell cycle, the surface
      expression of Tac antigen, and the release of soluble IL2 receptor and soluble
      CD8 were analyzed. When CsA and RAP were included in the stimulated CD8+
      lymphocyte cultures, these responses were inhibited. OKT3-stimulated CD8+
      lymphocytes were sensitive to lower concentrations of the immunosuppressants than
      those previously reported for peripheral blood mononuclear cells. RAP was
      effective at a lower dose than CsA and when the agents were applied in
      combination, cell proliferation was synergistically inhibited. These results
      demonstrate that CsA and RAP can inhibit the activation and proliferation of
      purified CD8+ lymphocytes in response to OKT3 or alloantigen in the presence of
      IL2.

PMID- 7586735
TI  - A CD3+CD8+ T cell population lacking CD5 antigen expression is expanded in
      peripheral blood of human immunodeficiency virus-infected patients.
AB  - In this study we analyzed the behavior of a CD3+ T cell subpopulation lacking CD5
      antigen expression in PBMC from HIV-1-infected patients. CD3+CD5- lymphocytes
      were greatly increased in peripheral blood of HIV-1+ patients, accounting for
      20.6 +/- 9.9% of the total CD3+ cells, compared to seronegative individuals (5.5
      +/- 3.2%). In both seropositive patients and controls, CD3+CD5- cells belonged to
      the CD8+ compartment; they were nonactivated, TCR alpha/beta+, naive lymphocytes,
      and in seronegative individuals preferentially expressed NK cell-associated
      markers, such as CD11b, CD16, CD56, and CD57. The phenotypic profile of this
      subset was slightly different in seropositive patients; while TCR expression and
      CD45RA/RO profile were comparable, CD11b and CD16 expression was lower compared
      to control figures, while CD56 expression was not changed, and CD57 expression
      was enhanced. Functional analysis of enriched CD3+CD8+CD5- cells showed an
      impaired ability to proliferate in response to mitogenic and antigenic stimuli;
      despite their NK-like phenotype, CD3+CD8+CD5- cells did not exert any NK
      cytotoxic activity, and only a lectin-dependent cytotoxic potential could be
      evidenced in this population. These results describe a novel alteration in the
      lymphocytes phenotypic profile during HIV-1 infection, involving a "transitional"
      population, which shares some properties of the T and of the NK cell lineage.

PMID- 7586736
TI  - Human immunodeficiency virus type 1 infection of CD4+ T cells down-regulates the
      expression of CD28: effect on T cell activation and cytokine production.
AB  - Infection with human immunodeficiency virus type 1 (HIV-1) results in
      dysregulation of normal T cell function. To study the effects of HIV-1 at the
      cellular level, primary T cell lines were generated by alloantigen stimulation of
      CD4+ T cells collected from peripheral blood of HIV-1-infected donors. Using
      Epstein-Barr virus-infected B lymphocytes (EBV-LCL) as a source of alloantigen,
      the T cell lines were expanded in vitro for 7 weeks. Uninfected T cell lines were
      cultured in parallel. Virus was inducible from the infected lines with
      stimulation, and complete infection was achieved after 4-7 weeks depending on the
      line. The down-modulation of CD28 expression correlated with virus replication
      and spread. Furthermore, CD28 mRNA was not inducible in the infected lines after
      stimulation with alloantigen. Loss of CD28 correlated with reduced responsiveness
      to costimulation with a monoclonal antibody to CD28 following similar engagement
      of the CD3 protein. In contrast, activation with alloantigen was not affected.
      HIV-1 infection and down-modulation of CD28 did not alter the relative levels of
      IL-2, IFN-gamma, and IL-4 mRNA. Production of the various cytokine mRNAs
      following alloantigen stimulation was inhibited by CTLA4Ig and thus remained
      under the regulation of CD80 and CD86 expressed on the EBV-LCL. Taken together,
      our data suggest that dysregulation of normal T cell function associated with HIV
      1 infection may result in part form the loss of CD28 expression.

PMID- 7586734
TI  - Proliferative responses of T cells from the skin and nerve lesions of leprosy
      patients.
AB  - In the current study we compared the mitogenic responses of T cells from skin and
      nerve biopsies of leprosy patients with those of peripheral blood mononuclear
      cells (PBMC). Lymphocytes from these sources were cultured at < or = 100
      cells/well in the presence of PHA, irradiated autologous feeder cells, and IL-2,
      and proliferation was assessed after 6 to 12 days. Whereas PBMC were capable of
      vigorous responses, the growth of cells from skin and nerve was markedly reduced.
      The diminished response was independent of the clinical status of leprosy
      patients and was also observed in skin-infiltrating lymphocytes from patients
      suffering from other disorders. Analysis of proliferative responses at 1
      cell/well suggested both a reduction in precursor frequency and a decrease in
      mean burst size. Analysis of lymphokine production suggested that cultured cells
      from skin lesions had reduced IL-w and IL-4 production relative to PBMC generated
      under similar conditions. Equal numbers of CD3+ cells were present in each
      source, but lesion cells were enriched in CD45RA- "memory" T cells, as well as
      CD3+CD28+ T cells. However, these alterations in subpopulation distribution could
      not account for the substantial differences in proliferative potential. We
      conclude that significant differences exist in the activation potential of cells
      from different tissue sources.

PMID- 7586733
TI  - Expression of adhesion molecules in early rheumatoid synovial tissue.
AB  - The objective of this paper is to define the expression of adhesion molecules in
      synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to
      disease duration. Antibodies against adhesion molecules were used for
      immunohistochemistry to examine ST sections from 11 patients with early RA ( < 1
      year), 14 patients with long-standing RA ( > 5 years), and 15 patients with
      osteoarthritis (OA). Increased cellular infiltration and increased expression of
      E-selectin, ICAM-1, VCAM-1, PECAM-1, VLA-4, and Mac-1 were found in ST from
      patients with RA compared to ST from patients with OA. The immunohistological
      findings were similar for the different stages of RA. The upregulation of
      adhesion molecules in ST of patients with RA of < 1 year's duration suggests the
      activation of chronic inflammatory processes in these patients. Therefore, the
      mechanisms by which therapies directed toward these adhesion molecules exert
      their effects are likely to be similar for patients with so-called early RA and
      patients with long-standing RA.

PMID- 7586737
TI  - A patient with autoimmune thrombocytopenic purpura demonstrating serum antibodies
      reactive with mouse cross-reactive idiotypes.
AB  - Autoimmune thrombocytopenic purpura (ATP) is a syndrome of destructive
      thrombocytopenia due to platelet-binding antibodies. We report the case of a
      young woman (C.V.) who has a history of chronic ATP with severe but transient
      bouts of thrombocytopenia. Using the classic monoclonal antibody (MAb)
      immobilization of platelet antigens (MAIPA) assay to screen serum antibody
      specificity, results were strongly positive with MAbs to glycoproteins (GPs) Ib
      IX, Ia-IIa, IV, and p24, but weakly positive or negative for GP IIb-IIIa. In
      contrast, a two-step incubation assay (MAIPA II), in which platelets were
      incubated sequentially with C.V. serum and the murine MAb, gave negative results
      for all GPs. Affinity chromatography performed using Bx-1, a MAb to GP Ib, showed
      that the patient's serum contained antibodies to determinants expressed by mouse
      immunoglobulins. These were present on Fab fragments on Bx-1. A survey of sera
      from other patients with thrombocytopenia of immune origin revealed that
      antibodies reactive with selected idiotypes of mouse MAbs were not infrequent and
      raises the question of their role in the thrombocytopenia.

PMID- 7586738
TI  - IgG autoantibody response in HTLV-I-infected patients.
AB  - Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum
      of clinical manifestation including adult T-cell leukemia (ATL) and tropical
      spastic paraparesis or HTLV-I-associated myelopathy (TSP/HAM). In most cases,
      however, infected patients remain asymptomatic. The participation of the immune
      system in the pathogenesis of TSP/HAM has been suggested. In this study the IgG
      antibody response of HTLV-I-infected individuals has been investigated using both
      ELISA with a panel of nuclear and cytoplasmic proteins and peptides known to be
      recognized by antibodies from patients with various systemic autoimmune diseases,
      and immunoprecipitation of ribonucleoproteins from HeLa cell extracts. The
      results were compared with the reactivity of sera from individuals with non-HTLV
      I-related neurological diseases and healthy blood donors. Raised levels of
      autoantibodies reacting with several nuclear and cytoplasmic antigens were found
      in TSP/HAM and ATL patients. In asymptomatic HTLV-I-seropositive individuals,
      both the prevalence and level of IgG antibodies were lower and directed only
      against a restricted set of antigens. The mechanism of induction of these
      antibodies still remains obscure. However, the results show that a significant
      autoimmune response exists in these patients and it may contribute to the
      pathogenesis of the disease.

PMID- 7586732
TI  - Absence of anti-idiotypic antibodies in IVIG preparations to autoantibodies of
      rare autoimmune diseases.
AB  - Intravenous immunoglobulins (IVIG) were found to contain anti-idiotypic
      antibodies against autoantibodies of various autoimmune diseases. We examined
      commercial IVIG preparations, from three different manufactures, for the presence
      of autoantibodies and anti-idiotypic antibodies of two rare autoimmune diseases-
      primary biliary cirrhosis [anti-pyruvate dehydrogenase (PDH) antibodies] and
      Goodpasture's syndrome (anti-NC1 antibodies). We used ELISA studies as well as
      immunoblotting and anti-PDH enzyme activity for the detection of anti-PDH
      antibodies. ELISA and immunofluorescence studies were used for the detection of
      anti-NC1 antibodies. The presence of anti-idiotypic activity against anti-PDH
      fragments on Sepharose-bound IVIG [F(ab)2]. Anti-anti-NC1 activity was evaluated
      employing inhibition ELISA and immunofluorescence studies. The commercial IVIG
      preparations that were examined did not contain anti-PDH or anti-NC1 antibodies
      nor anti-idiotypic activity against these autoantibodies. We conclude that
      commercial IVIG may lack anti-idiotypic activity against rare autoantibodies.

PMID- 7586740
TI  - Investigation of EB virus and cytomegalovirus in rapidly progressive interstitial
      pneumonitis in polymyositis/dermatomyositis by in situ hybridization and
      polymerase chain reaction.
AB  - In polymyositis/dermatomyositis (PM/DM), a rapidly progressive interstitial
      pneumonitis (RPIP) which is a fatal complication of unknown etiology has received
      increasing attention. We have encountered 9 RPIP cases among 150 PM/DM cases in
      the past 10 years. To investigate the pathogenic role of viruses in RPIP, we
      examined lung specimens from patients with RPIP in PM/DM for the presence of
      Epstein-Barr virus (EBV) and cytomegalovirus (CMV) using polymerase chain
      reaction (PCR) and in situ hybridization (ISH). We analyzed 21 specimens from
      RPIP in PM/DM (n = 9), collagen diseases (n = 6; 4 had interstitial lung
      disease), and controls (n = 6). EBV was frequently detected in RPIP (7/9 by PCR
      3/9 by ISH), but was also detected in other collagen diseases of the lungs. In
      lung specimens from both patients with RPIP in PM/DM and those with collagen
      diseases, EBV was significantly detected (13/15 by PCR, 5/15 by ISH, P < 0.005)
      compared to controls (1/6 by PCR, 0/6 by ISH). CMV was detected by ISH in 2 RPIP
      patients but in none of he others, though by PCR CMV was detected equally in the
      three groups studied. These findings indicate that a direct involvement of EBV or
      CMV in RPIP of PM/DM is unlikely, although it is possible that an immune response
      to latent viruses or viral products in PM/DM may have a role in the pathogenesis
      of the RPIP.

PMID- 7586739
TI  - Genetic susceptibility to silver-induced anti-fibrillarin autoantibodies in mice.
AB  - Similar to mercuric chloride, silver nitrate has recently been shown to induce
      IgG autoantibodies targeting the nucleolar 34-kDa protein fibrillarin i SJL (H
      2s) mice. In the present study we show that the autoimmunogenic effect of silver
      is dependent on intact T-cell function since SJL/N mice homozygous for the nude
      mutation (athymic), in contrast to the functionally T-cell-intact SJL/N-nu/+
      littermates, did not develop anti-nucleolar/anti-fibrillarin autoantibodies
      (ANoA/AFA). The genetic susceptibility for silver-induced AFA was localized to
      the H-2A locus using congenic and intra-H-2-recombinant strains. However,
      background (non-H-2) genetic factors substantially influenced both the response
      rate and the titer of ANoA/AFA attained. Strains bearing H-2As on the SJL and A
      backgrounds (SJL, A.SW, A.TH) showed 100% response rate and high ANoA titers
      (3750 +/- 246, mean reciprocal titer +/- SEM), whereas H-2As mice on the B10
      background (B10.S) showed 60% response rate and significantly lower ANoA titers
      (1170 +/- 305) in the responding mice. Expression of H-2E [B10.S(9R) mice]
      further reduced the response rate (22%) and the ANoA titer (640 +/- 0). A
      suppressive effect on the B10 background has previously been observed in mercury
      treatment, but the effect was stronger in silver-treated mice. Two major
      differences were noted between silver- and mercury-induced murine autoimmunity.
      First, silver-treated mice did not show elevated titers of other autoantibody
      specificities, specifically not of antichromatin and anti-histone antibodies,
      which develop in mercury-treated SJL mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586742
TI  - Cutaneous immunopathology of cyclosporin-A-induced autoimmunity in the rat.
AB  - Syngeneic bone marrow transplantation following lethal X-irradiation and
      subsequent administration of cyclosporin A (CsA) results after cessation of CsA
      treatment in an autoimmune disease which is thymus dependent and resembles graft
      versus-host disease. The chronic dermal changes of this experimental autoimmune
      model have similarities with human scleroderma in terms of skin histopathology.
      In this study we evaluated the possible role of different effector leukocytes in
      the rat model of CsA-induced autoimmunity (CsA-AI) by examining the skin by
      immunohistology. In the acute phase both CD4+ and CD8+ TCR alpha beta + T-cells
      together with activated ED1+ macrophages and class II MHC-upregulated
      keratinocytes were seen in the epidermis; no selective use of TCR V beta was
      observed. Few TCR alpha beta + T-cells were seen in the dermis where CD4+ ED2+
      macrophages were abundant. With the change from acute to chronic, scleroderma
      like lesions the CD4+ T-cells disappeared from the epidermis and the TCR alpha
      beta + cells were now almost exclusively CD8+; both class II MHC-upregulated
      keratinocytes and macrophages persisted. Changes in TCR gamma delta + T-cells
      were not observed in the acute or chronic phase. As a possible effector mechanism
      CD4+ T-cells in the acute-phase of CsA-AI may cause the observed activation of
      macrophages and keratinocytes. Furthermore, CD4+ T-cells may be necessary for the
      homing of the CD8+ T-cells in the epidermis. Especially the activated
      keratinocytes are suspected of being the target cells which may perpetuate the
      ongoing autoimmune response into the chronic phase as established by CD8+ T-cells
      only.

PMID- 7586741
TI  - Macrophage inflammatory protein-1 beta: a C-C chemokine in osteoarthritis.
AB  - The aim of this study was to determine whether the cytokine macrophage
      inflammatory protein-1 beta (MIP-1 beta) is present and functionally active in
      the arthritic joint. We used immunoassays and bioassays to assess the presence
      and function of MIP-1 beta using samples obtained from 62 arthritic patients. MIP
      1 beta levels were increased in synovial fluids (SFs) from patients with
      osteoarthritis (OA) (18.0 +/- 8.9 ng/ml) (SD) compared to patients with
      rheumatoid arthritis (RA) 6.1 +/- 2.9 ng/ml) or other forms of arthritis (10.4 +/
      7.0 ng/ml) (P < 0.05). Levels of OA SF MIP-1 beta were significantly greater
      than OA or normal serum levels of MIP-1 beta. Anti-MIP-1 beta neutralized 28% of
      the chemotactic activity for monocytes found in OA SFs. Isolated OA synovial
      tissue fibroblasts did not constitutively produce MIP-1 beta but could be induced
      to express this chemokine upon exposure to tumor necrosis factor-alpha,
      interleukin-1 beta, or lipopolysaccharide. Synovial tissue immunohistochemical
      staining revealed that the main immunopositive cells in OA were the lining cells
      as well as vascular smooth muscle and endothelial cells. A minority of
      macrophages were immunopositive as well. In this study, we identify MIP-1 beta as
      a unique cytokine increased in OA compared to RA SF. We conclude that MIP-1 beta
      may play a role in the ingress of monocytes into the OA joint.

PMID- 7586745
TI  - Treatment of arthritis in Lewis rats by a monoclonal antibody against alpha beta
      T cell receptor: differential sensitivity of Yersinia-induced arthritis versus
      adjuvant arthritis.
AB  - Lewis rats experimentally infected with Yersinia enterocolitica develop sterile
      arthritis similar to Yersinia-associated reactive arthritis in humans. To
      investigate the putative role of alpha beta T cells in the pathogenesis of
      Yersinia-induced arthritis (YIA) rats were treated with the monoclonal antibody
      (mAb) R73 mAb directed against the rat alpha beta T cell receptor. In spite of
      reduction of alpha beta T cells in peripheral blood and in liver lesions of
      Yersinia-infected rats this serotherapy had no suppressive effect on YIA.
      Moreover, R73 mAb treatment had no influence on the number of alpha beta T cells
      in the inflammed synovial tissue. In contrast, R73 mAb serotherapy in
      Mycobaterium tuberculosis-immunized rats blocked development of adjuvant
      arthritis (AA) and suppressed the presence of alpha beta T cells in the synovial
      tissue. These results suggest fundamental differences between the immunopatho
      mechanism of YIA caused by bacterial infection and AA induced by bacterial
      immunization and known to be T cell mediated. These data might have consequences
      for putative serotherapy of arthritis in humans.

PMID- 7586744
TI  - Modulatory effects of staphylococcal superantigen TSST-1 on IgE synthesis in
      atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic skin disorder associated with elevated serum
      IgE and colonization of the skin by Staphylococi which secrete toxins with
      superantigenic activity. The present study examined the immunomodulatory effects
      of toxic shock syndrome toxin (TSST)-1, a prototypic superantigen, on IgE
      synthesis by interleukin (IL)-4-stimulated peripheral blood mononuclear cells
      (PBMC) from five patients with AD and five normal subjects. TSST-1 inhibited IL-4
      induced IgE synthesis by AD and normal PBMC (P < 0.05). In contrast, IgG
      synthesis was not similarly affected (P > 0.30). Inhibition of IL-4-induced IgE
      production was associated with induction of interferon (IFN)-gamma synthesis by
      TSST-1 (P < 0.02). Normal PBMC synthesized significantly more (P < 0.005) IFN
      gamma than AD PBMC. A neutralizing antibody to IFN-gamma reversed TSST-1-induced
      suppression of IgE synthesis by the normal PBMC (P < 0.03), but not the AD PBMC.
      In AD, but not normal, PBMC anti-IFN-alpha antibody reversed the suppression of
      IgE synthesis induced by TSST-1. These results demonstrate that TSST-1 uses
      different mechanisms for modulation of IgE synthesis in AD versus normal PBMC.
      Furthermore, the reversal of TSST-1-induced suppression of IgE synthesis in AD
      PBMC by anti-IFN-alpha, but not anti-IFN-gamma, is consistent with the concept
      that AD is associated with defective Th1 cell function and enhanced monocyte
      activity.

PMID- 7586746
TI  - Distinct production of autoantibodies to nuclear components in ulcerative colitis
      and in Crohn's disease.
AB  - Despite extensive research, the pathogenesis of inflammatory bowel disease (IBD)
      is still unclear. Immunological disorders have been described in patients with
      both Crohn's disease (CD) and ulcerative colitis (UC). In this work serum samples
      collected from 58 patients with CD and 55 patients with UC were tested in ELISA
      against a panel of nuclear and cytoplasmic proteins and peptides in order to
      determine whether specific autoantibodies are produced in these patients. Low
      levels of IgG antibodies to histones H1, H2A, H2B, H3, and H4, to Hsp-70 and
      ubiquitin stress proteins, Ro/SSA and La/SSB proteins and myosin were detected in
      some of these sera. In contrast, the following antibodies of IgG isotype could be
      much more frequently demonstrated: antibodies to ubiquitinated H2A (U-H2A)
      peptide T4 (51.7% in CD; 18.2% in UC), antibodies to the zinc-finger peptide F2
      of poly-(ADP-ribose polymer)ase (PARP) involved in DNA repair (58.6% in CD; 25.5%
      in UC) and actin antibodies (43.1% in CD; 7.3% in UC). In a follow-up study of 12
      patients with CD and UC (75 additional samples), we found IgG antibodies to
      several histone peptides occurring essentially in the serum of patients with CD.
      Although we found no obvious correlation between the presence or level of these
      various antibodies and C-reactive protein, or the location of the disease, in a
      number (but not all) of patients, we observed a strikingly good relationship
      between antibodies to histone peptides, U-H2A peptide T4, and PARP peptide F2 and
      the Crohn's disease activity index. The mechanism of induction of these
      antibodies still remains obscure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586743
TI  - Differential effect of TGF-beta 1 on the in vitro activation of HTLV-I and the
      proliferative response of CD8+ T lymphocytes in patients with HTLV-I-associated
      myelopathy (HAM/TSP).
AB  - While considerable information is available on the pathogenesis of human T
      lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP), fundamental questions remain unanswered. In particular the
      clinicopathological uniformity of the disorder among patients remains poorly
      understood. The potential role of TGF-beta as a preferential immune regulator in
      the CNS and the functional heterogeneity of TGF-beta has led us to assess the
      possible involvement of this cytokine in the pathogenic process. To investigate
      this, the modulatory effects of TGF-beta 1 on HTLV-I-induced in vitro phenomena
      were evaluated using fractionated lymphocytes from patients with HAM/TSP. It
      could be shown that the proliferative response of CD8+ cells against cultured and
      irradiated autologous CD4+ cells possessing HTLV-I antigens was significantly
      inhibited by TGF-beta 1. However, the in vitro activation of HTLV-I, which was
      evaluated by spontaneous proliferation of CD4+ cells, was unaffected by TGF-beta
      1. The induction of intracytoplasmic HTLV-I antigens in cultured CD4+ cells was
      facilitated by TGF-beta 1 in a dose-dependent manner. These findings suggest that
      TGF-beta may have a critical role in localized viral activation within the CNS in
      patients with HAM/TSP.

PMID- 7586748
TI  - IgG anti-F(ab')2 antibodies from SLE patients react with immunodominant residues
      in kappa CDRs, but show reduced C kappa region reactivity.
AB  - We studied reactivity of affinity-purified human IgG anti-F(ab')2 antibodies for
      antigenic determinants on kappa light chains. Variable (VL) and constant (CL)
      regions of a human kappa I light chain (EU) were studied for enzyme-linked
      immunosorbent assay reactivity with monoclonal anti-k antibodies and human IgG
      antiF(ab')2 using overlapping heptamers of primary sequence synthesized as
      peptides on polypropylene pins. Polyclonal IgG anti-F(ab')2 antibodies isolated
      by affinity chromatography from the serum of patients with systemic lupus
      erythematosus (SLE) were found to react primarily with CDR1- and CDR3-related
      peptides. The most reactive residues included IL29, TRY32, LEU33, ALA34, GLU90,
      TYR91, and ASN 92. No striking difference in overall V-region anti-F(ab')2
      reactivity profiles was noted when 10 IgG anti-F(ab')2 preparations from normal
      subjects and SLE patients were compared. In contrast, however, when tested
      against overlapping C kappa heptamer sequences, the reactivity in SLE-associated
      anti-F(ab')2 antibodies was markedly decreased. We report that this difference
      may reflect a defect in anti-idiotypic control mechanisms in SLE.

PMID- 7586747
TI  - Tumor necrosis factor-alpha mediates the release of bioactive transforming growth
      factor-beta in murine microglial cell cultures.
AB  - Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta
      produced by glial cells have been proposed bo play a role in various
      neurodenegerative diseases. The interaction of these two cytokines, however, is
      unknown. We tested the hypothesis that the TNF-alpha released from
      lipopolysaccharide (LPS)-treated murine microglial cells would stimulate the
      release of TGF-beta, which in turn would control TNF-alpha production. Treatment
      of murine microglial cell cultures with LPS resulted in an acute release of TNF
      alpha (peak by 8 hr) followed by delayed release of bioactive TGF-beta (peak by
      48 hr). Anti-TNF-alpha antibody significantly inhibited LPS-stimulated TGF-beta
      production, suggesting the involvement of TNF-alpha in TGF-beta production. Also,
      exogenous TNF-alpha induced in a dose-dependent fashion microglial cell
      expression of TGF-beta 1 mRNA and release of TGF-beta. Exogenous TGF-beta, on the
      other hand, suppressed LPS-stimulated TNF-alpha release. These findings suggest
      an autoregulation of microglial cell TNF-alpha production by TGF-beta which may
      limit inflammation-associated brain injury.

PMID- 7586749
TI  - A macromolecular multicomponent peptide vaccine prepared using the glutaraldehyde
      conjugation method with strong immunogenicity for HIV-1.
AB  - The immunogenicity of a newly constructed macromolecular multicomponent peptide
      vaccine candidate against human immunodeficiency virus type 1 (HIV-1) was
      compared with that of previously reported vaccine candidates. This vaccine
      candidate is composed of a macromolecular multicomponent peptide complex
      consisting of three V3 region peptides, one Gag region peptide, and CD4-binding
      site peptide and was constructed using the multiple-antigen peptide and
      glutaraldehyde methods. Sera from rabbits immunized with this newly constructed
      vaccine showed strong antibody titers against each constituent peptide antigen.
      Furthermore, these antibodies exhibited strong neutralizing and antifusion
      activity toward HIV-1IIB, HIV-1MN, and fresh isolates from Japanese HIV
      seropositive individuals. These results show that this new vaccine candidate has
      the capacity to induce strong, polyvalent immunogenicity and therefore may prove
      to be a powerful peptide vaccine against HIV-1 infection.

PMID- 7586750
TI  - MHC class I and class II determinants and some adhesion molecules are engaged in
      the regulation of nitric oxide production in vitro by human monocytes stimulated
      with colon carcinoma cells.
AB  - Surface molecules that are involved in tumor-monocyte interactions were studied.
      The in vitro system in which human blood monocytes are stimulated with human
      colon carcinoma cells for nitric oxide (NO) production was used. Monoclonal
      antibodies (mAbs) against various adhesion molecules (LFA-1, ICAM-1, VNR) were
      unable to block NO production in coculture of monocytes with carcinoma cells.
      However, anti-CD44, -LFA-3, and -VLA beta 1 chain mAbs effectively blocked NO
      production. Also mAbs against MHC class I and HLA-DR molecules inhibited, in a
      dose-dependent manner, No release. It was concluded that some adhesion molecules
      and MHC class I and/or class II determinants of monocytes may be involved in
      tumor-monocyte interactions leading to signal transduction for NO production.

PMID- 7586751
TI  - Vertebrate gastrulation and axial patterning: editorial overview, Part 2.

PMID- 7586752
TI  - Differential expression of fork head genes during early Xenopus and zebrafish
      development.
AB  - Intense efforts have been devoted to the identification of genes that are
      causatively involved in pattern-forming events of invertebrates and vertebrates.
      Several gene families involved in this process have been identified. Here we
      focus on the Xenopus fork head domain gene family. One of its members,
      XFKH1/Pintallavis/XFD1, has been shown previously to be involved in axial
      formation, and the expression patterns of the other family members discussed
      below suggest that they too play a major role in the initial steps of patterning
      and axial organization. In this report, we describe four Xenopus fork head genes
      (XFKH3, 4, 5, and 6) and analyze the distribution of their transcripts during
      early development. XFKH3 is expressed in developing somites but not notochord,
      XFKH4 in forebrain, anterior retina, and neural crest cells, and XFKH5 in a
      subset of epidermal cells and the neural floor plate. Finally, transcripts of
      XFKH6 are seen in neural crest-derived cranial ganglia. In addition, we show that
      at least some of the zebrafish fork head genes might serve a comparable function.
      Zebrafish zf-FKH1 has a similar expression pattern as Xenopus
      XFKH1/Pintallavis/XFD1. It is transcribed in the notochord and neural floor
      plate. The polster or "pillow" also shows very high levels of zf-FKH1 mRNA.

PMID- 7586753
TI  - Widespread expression of the eve1 gene in zebrafish embryos affects the anterior
      posterior axis pattern.
AB  - The zygotic expression of the eve1 gene is restricted to the ventral and lateral
      cells of the marginal zone. At later stages, the mRNAs are localized in the most
      posterior part of the extending tail tip. An eve1 clone (pcZf14), containing a
      poly-A tail, has been isolated. In order to address eve1 gene function, pcZf14
      transcript injections into zebrafish embryos have been performed. The injection
      into uncleaved eggs of a synthetic eve1 mRNA (12 pg), which encodes a protein of
      approximately 28 kd, produces embryos with anterior-posterior (A-P) axis defects
      and the formation of additional axial structures. The first category of 24 h
      phenotypes (87%) mainly displays a gradual decrease in anterior structures. This
      is comparable to previous phenotypes observed following Xhox3 messenger injection
      either in Xenopus or in zebrafish that have been classified according to the
      index of axis deficiency (zf-IAD). These phenotypes result in anomalies of the
      development of the neural keel, from microphthalmia to acephaly. The second
      category (13%) corresponds to the phenotypes described above together with
      truncal or caudal supernumerary structures. Additional truncal structures are the
      most prominent of these duplicated phenotypes, displaying a "zipper" shape of
      axial structures including neural keels and notochords. Caudal duplication
      presents no evident axis supernumerary structures. The observation of these
      phenotypes suggests an important role for the eve1 gene in mesodermal cell
      specification and in the development of the posterior region, and more
      particularly of the most posterior tail tip where endogenous eve1 messengers are
      found.

PMID- 7586754
TI  - Involvement of wnt1 and pax2 in the formation of the midbrain-hindbrain boundary
      in the zebrafish gastrula.
AB  - The secreted signalling molecule encoded by the wnt1 gene and the paired box
      containing pax2 gene are thought to play an integral role in patterning the
      zebrafish rostral nervous system. Using a double-label analysis, we compare the
      expression patterns of wnt1 RNA and pax2 protein during zebrafish embryogenesis
      to determine whether they were expressed in identical or overlapping patterns in
      individual embryos. During gastrulation, wnt1 RNA was detected in a pattern
      similar but not identical to the pax2 protein. Later, wnt1 and pax2 co-localize
      to the midbrain-hindbrain boundary. Exogenous retinoic acid, a teratogen that is
      known to affect the formation of the midbrain-hindbrain boundary, has a profound
      affect on both wnt1 and pax2 expression at gastrulation. Furthermore, when pax2
      is overexpressed in zebrafish embryos, the wnt1 pattern of expression expands
      ventrally in the prospective rostral neuroepithelium. Despite the widespread and
      random distribution of exogenous pax2 RNA, it alone is unable to induce wnt1
      expression in other ectopic sites. These results are consistent with the
      coordinate expression of wnt1 and pax2 being in a pathway responsible for
      establishing the midbrain-hindbrain boundary and support the earlier
      interpretation that pax2 may regulate wnt1 expression [Krauss et al., 1992],
      although only in a subset of embryonic cells. These data suggest that a
      predisposition for the regionalization of the central nervous system exists at
      gastrulation.

PMID- 7586756
TI  - Cell fate decisions in the early embryo of the nematode Caenorhabditis elegans.

PMID- 7586755
TI  - Characterization of a gene trap insertion into a novel gene, cordon-bleu,
      expressed in axial structures of the gastrulating mouse embryo.
AB  - We have used a gene trap (GT) vector and embryonic stem (ES) cell chimeras to
      screen for insertions of the lacZ reporter gene into transcription units that are
      spatially and temporally regulated during early mouse embryogenesis. GT vectors
      which can act as both a reporter and a mutagen have been previously used to
      isolate new genes that are essential for mouse development. In this paper we
      describe a GT insertion which displays a very restricted pattern of expression in
      the gastrulating embryo. beta-Galactosidase activity was first detected at 7.5
      days post-coitum (E7.5) in the node region of the embryo and extended to the
      midline structures at E8.0. At E9.5 expression was restricted to the floor plate,
      the notochord, the roof of the gut, and the liver anlage. Expression appeared in
      the somites at E10.0 and later became more widespread. We used rapid
      amplification of cDNA ends-polymerase chain reaction (RACE-PCR) to clone a
      partial 360 base pair (bp) cDNA representing an endogenous sequence and
      containing an open reading frame (ORF) fused in frame to the lacZ reporter gene.
      The sequence showed no homology to any known protein or protein domain. An
      overlapping 1,200 bp fragment from a wild-type cDNA library was cloned and it
      detected the same pattern of expression as the reporter gene in E7.5, E8.5, and
      E9.5 wild-type embryos. It hybridized to a 5.4 kb lacZ fusion transcript and to
      an endogenous transcript of 6.5 kb. The gene was mapped to chromosome 11 and was
      named cordon-bleu (cobl). No phenotype was detected in mice homozygous for the
      insertion. However, the insertion may not cause a complete disruption of the gene
      function. The pattern of expression of cobl is very similar to that of hepatic
      nuclear factor 3 beta (HNF3 beta) and sonic hedgehog (Shh), both of which are
      involved in axial patterning. Therefore, the product of the cobl gene may also
      prove to be an important component of the genetic pathway regulating vertebrate
      axis formation.

PMID- 7586759
TI  - Safety and data monitoring committees for clinical trials.

PMID- 7586757
TI  - Epithelial proliferation and differentiation in the mammary gland do not
      correlate with cFABP gene expression during early pregnancy.
AB  - Cardiac fatty acid binding protein (cFABP) is abundantly expressed in the
      nondividing, functionally differentiated mammary epithelium. It is very closely
      related, if not identical to, a previously described protein termed mammary
      derived growth inhibitor (MDGI). In vitro studies suggest that low concentrations
      of diffusible cFABP/MDGI may play a hormone-like role in limiting proliferative
      activity and promoting functional differentiation of this tissue, but no in vivo
      data to support this idea have been published. To test this hypothesis, we
      compared the levels of cFABP mRNA with both the epithelial DNA labelling index
      and levels of beta-casein mRNA in wild-type mice. We also investigated the effect
      of a precocious experimental increase of cFABP levels in the mammary gland of
      transgenic mice on the labelling index and beta-casein mRNA levels. This was
      accomplished by expressing a bovine cFABP cDNA under the control of the ovine
      beta-lactoglobulin (BLG) gene promoter. We found that although both the DNA
      labelling index, beta-casein mRNA levels, and cFABP mRNA levels in wild-type mice
      are developmentally regulated, they do not correlate with each other during early
      pregnancy in individual mice. Moreover, a three- to fourfold increase of total
      cFABP mRNA in two transgenic lines did not affect the DNA labelling index or the
      levels of beta-casein mRNA, an established marker of differentiation of the
      mammary epithelium, at this developmental stage. These data suggest that
      epithelial DNA synthesis, beta-casein gene expression, and expression of the
      cFABP gene are regulated independently in the proliferatively active mammary
      gland and that the rapidly dividing mammary epithelial cells are not susceptible
      to the action of cFABP during early pregnancy.

PMID- 7586758
TI  - Involvement of differential gene expression and mRNA stability in the
      developmental regulation of the hsp 30 gene family in heat-shocked Xenopus laevis
      embryos.
AB  - Four complete hsp 30 genes have been isolated from Xenopus laevis: hsp 30A, hsp
      30B (a pseudogene), hsp 30C, and hsp 30D. The hsp 30A and hsp 30C genes are first
      heat inducible at the early tailbud stage, as determined by RNase protection and
      RT-PCR assays. In this study, we determined by RT-PCR that the hsp 30D gene was
      first heat inducible (33 degrees C for 1 h) at the mid-tailbud stage,
      approximately 1 day later in development than hsp 30A and hsp 30C. Furthermore,
      using Northern blot analysis, we detected the presence of very low levels of hsp
      30 mRNA at the heat-shocked late blastula stage. The relative levels of these pre
      tailbud (PTB) hsp 30 mRNAs increased at the gastrula and neurula stage followed
      by a dramatic enhancement in heat shocked tailbud and tadpole stage embryos (50-
      to 100- fold relative to late blastula). Interestingly, treatment of blastula or
      gastrula embryos at high temperatures (37 degrees C for 1 h) or with the protein
      synthesis inhibitor, cycloheximide, followed by heat shock, led to enhanced
      accumulation of the pre-tailbud (PTB) hsp 30 mRNAs. hsp 70, hsp 87, and actin
      messages were not stabilized at high temperatures or by cycloheximide treatment.
      Finally, hsp 30D mRNA was not detected by RT-PCR analysis of cycloheximide
      treated, heat-shocked blastula stage embryos, confirming that it is not a member
      of the PTB hsp 30 mRNAs. This study indicates that differential gene expression
      and mRNA stability are involved in the regulation of hsp 30 gene expression
      during early Xenopus laevis development.

PMID- 7586760
TI  - Electrocardiographic interpretation (1995): can we do better?--Part I.

PMID- 7586761
TI  - Neuroendocrine changes in heart failure and their clinical relevance.
AB  - The pathophysiology of heart failure is closely associated with neuroendocrine
      changes. Activation of these humoral systems apparently serves as a compensatory
      mechanism for the failing circulation. However, overshoot of such mechanisms may
      further depress cardiac function by increasing afterload, resulting in a vicious
      cycle of reflex neuroendocrine activation. Corollary decreases in renal function
      activate the renin-angiotensin-aldosterone system as well, which further
      contributes to the cycle of downward-spiralling cardiac function. Many hormonal
      factors are increased in congestive heart failure. While some influences are
      vasodilatory, the net effect is marked vasoconstriction. The level of activation
      of these systems apparently corresponds to the severity of heart failure.
      Furthermore, elevated levels of these hormones, including norepinephrine, atrial
      natriuretic factor, plasma renin, and plasma arginine vasopressin, may play a
      more direct role in worsening heart failure. In fact, elevated catecholamine
      levels are directly related to prognosis. Catecholamines increase myocardial
      oxygen demand and are also arrhythmogenic. Oral catecholamines and
      phosphodiesterase inhibitors, which work by similar mechanisms, have yielded
      increased mortality rates in heart failure trials. In contrast, mortality rates
      are reduced in patients treated with angiotensin-converting enzyme inhibitors.
      Thus, it is clear that neuroendocrine changes are not only a marker of the
      severity of heart failure, but also directly worsen it. Interventions that
      antagonize or diminish these neuroendocrine changes apparently benefit patients
      with heart failure.

PMID- 7586762
TI  - Preoperative strategies to assess cardiac risk before noncardiac surgery.
AB  - The strategies recommended in the preoperative cardiac risk assessment prior to
      major vascular and nonvascular surgery are reviewed. The role of clinical
      evaluation, noninvasive stress testing (exercise test, stress myocardial
      perfusion imaging, stress echocardiography), and Holter monitoring during the
      preoperative evaluation are outlined and the value of intervention based on the
      use of each test is discussed. Recommended strategies to evaluate patients based
      on their clinical risk markers in addition to the results of the noninvasive risk
      assessment are presented.

PMID- 7586763
TI  - Early hemodynamic effects at rest with acute and chronic isosorbide dinitrate
      treatment in patients with ischemic heart disease.
AB  - Asymmetric dosage regimens are used to circumvent development of nitrate
      tolerance and are believed to restore totally the hemodynamic responsiveness to
      an acute dosage of nitrates. This study assessed invasively the hemodynamics
      during supine rest before and for 50 min after peroral 30 mg isosorbide dinitrate
      (ISDN) in 16 patients with stable ischemic heart disease; 8 previously untreated
      patients (NT group) and 8 patients treated asymmetrically b.i.d. with 30 mg ISDN
      for 14 days prior to the invasive investigation (T group). Before initiation of
      treatment, both groups had identical mean arterial pressure (MAP) and heart rate
      (HR). On the day of invasive investigation, before intake of ISDN, MAP was higher
      in the T group but unchanged in the NT group. After the intake of ISDN, right
      atrial pressure (RAP), mean pulmonary arterial pressure, and pulmonary arterial
      wedge pressure declined markedly within 10 to 15 min in both groups, while MAP
      showed a more protracted decline, reaching a new level only after 25 to 30 min.
      In the NT group, HR accelerated markedly and remained elevated throughout the
      observation period, whereas in the T group HR showed no significant alteration
      after ISDN intake. At the end of the observation period, the cardiac index (CI)
      was definitely reduced in the NT group, but remained unchanged in the T group,
      while the systemic vascular resistance index was unchanged in the former and was
      clearly reduced in the latter. It is concluded that the fall in MAP in the NT
      group was solely due to a fall in CI, and that the decline in RAP and venous
      return in the NT group induced neurohumoral reflexes leading to a rise in HR and
      prevention of arterial dilation, whereas in the T group, already influenced by
      chronic treatment, such acute counterregulatory responses were markedly
      attenuated or absent.

PMID- 7586764
TI  - Treatment of acute myocardial infarction with streptokinase does not appear to
      modulate circulating neutrophil function.
AB  - The administration of thrombolytic therapy is the most common method of achieving
      patency of the occluded coronary artery in patients with acute myocardial
      infarction (AMI). However, thrombolytic agents and the byproducts of fibrinolysis
      have the potential to affect neutrophil activation and thus function, thereby
      augmenting myocardial damage further. This study assessed the effect of
      streptokinase administration on the function of circulating neutrophils in
      patients with AMI. For this neutrophil adherence to human umbilical vein
      endothelial cells, homotypic neutrophil aggregation, and CD11b and L-selectin
      expression on the neutrophil membrane prior to and 1 h and 6 h after thrombolytic
      therapy was monitored. The study population included patients with AMI who
      received aspirin and streptokinase, and healthy laboratory workers who received
      aspirin only; all subjects acted as their own controls. Circulating fibrin
      degradation products and white cells were markedly raised following
      administration of streptokinase. No significant differences in neutrophil
      adherence to endothelium, homotypic neutrophil interactions, and CD11b or L
      selectin expression were demonstrated between neutrophils, either pre- or post
      thrombolytic therapy in the infarct group, or between neutrophils from the
      infarct group and from the control group. It was concluded that streptokinase
      produces an abrupt neutrophil leukocytosis together with a marked increase in
      circulating levels of fibrin degradation products. The assay systems used were
      unable to show significant sequential changes in circulating neutrophil adhesion
      and L-selectin or CD11b expression in patients with AMI following thrombolytic
      therapy or when these patients were compared with controls.

PMID- 7586766
TI  - The effects of age and gender on brachial artery endothelium-dependent
      vasoactivity are stimulus-dependent.
AB  - Impaired endothelium-dependent vasomotion in response to flow-mediated,
      cholinergic, and cold pressor stimulation has been demonstrated in the presence
      of both atherosclerosis and cardiac risk factors. This study investigated the
      effects of different vasoactive stimuli on brachial artery vasomotion with
      respect to age and gender. Forty healthy subjects (20 men and 20 women), ages 23
      to 52 years, were studied. Using 7.5 MHz ultrasound, brachial artery diameter and
      Doppler flow velocity at baseline, following 5 min of ipsilateral blood pressure
      cuff occlusion (flow-mediated), during contralateral hand immersion in ice (cold
      pressor) and after sublingual nitroglycerin administration, were measured in
      older subjects (> 40 yrs) and younger subjects (< 40 yrs). Among normal subjects,
      % diameter change in response to the flow-mediated stimulus was less in older men
      than in younger men (6.8 +/- 3.2% vs. 11.5 +/- 7.4%, p < 0.05); older and younger
      women had comparable responses (10.0 +/- 5.3% vs. 11.6 +/- 4.3%, p = NS). With
      cold pressor, normal older men and older women vasoconstricted (-1.2 +/- 0.9%, 
      2.2 +/- 4.7%) compared with younger subjects who vasodilated (1.4 +/- 2.5%, 0.6
      +/- 2.3%, p < 0.02). The cold pressor test elicited comparable responses among
      older normal subjects. Nitroglycerin, a non-endothelium-mediated stimulus,
      induced significant vasodilatation in all the groups. In conclusion, endothelium
      mediated responses in subjects of varying age and gender are stimulus-dependent.
      Flow-mediated vasodilatation could not differentiate older premenopausal women
      from younger women; cold pressor stimulus could.

PMID- 7586765
TI  - Captopril in acute myocardial infarction: beneficial effects on infarct size and
      arrhythmias.
AB  - It is known from experiments that angiotensin-converting enzyme inhibitors can
      limit infarct size. In a prospective, randomized, placebo-controlled double-blind
      study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were
      given placebo. Medication was started between 2 and 18 h from the onset of
      infarction. The two groups were matched for age, infarct location, and time of
      intervention. With the exception of one patient in either group, all were
      concurrently given nitroglycerin. The necrosis parameters were provided by the
      quantitative measurement of the QRS complex. The Q wave decreased with captopril
      treatment (-0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The
      number of ventricular premature beats at 24 h from the start of treatment was
      25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation
      occurred seven times in the placebo group, but did not occur in the captopril
      group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with
      placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced
      by 12 mmHg with captopril treatment. The results show a beneficial effect of
      captopril on infarct size and electrical instability, over and above the effect
      of standard management with nitroglycerin and thrombolysis.

PMID- 7586767
TI  - Intracardiac thrombi: frequency, location, etiology, and complications: a
      morphologic review--Part I.
AB  - Intracardiac thrombus is a frequent finding at necropsy. Various cardiac
      disorders have been associated with its presence. Part I of this 5-part article
      focuses on classification by location and etiology and reviews primary
      cardiomyopathy as a specific condition associated with intracardiac thrombus.

PMID- 7586769
TI  - Thymoma with pericardial tamponade.
AB  - Thymomas are tumors of the anterior mediastinum. They are most often seen in
      adults aged 45 to 50 years. These tumors are routinely asymptomatic for prolonged
      periods of time. The most common presentation is discovery on routine chest x
      ray. We therefore present a case report of an elderly woman who presented with
      symptoms of dyspnea caused by a malignant thymoma. To our knowledge, symptomatic
      pericardial tamponade due to a thymoma with a massive pericardial effusion has
      not been described previously.

PMID- 7586770
TI  - Homer W. Smith and his contribution to cardiovascular medicine.

PMID- 7586771
TI  - Silicone breast implants and connective-tissue diseases.

PMID- 7586768
TI  - Coronary angioplasty for the control of intractable ventricular arrhythmia.
AB  - Ventricular arrhythmias (VAs) that occur following an acute extensive anterior
      myocardial infarction (MI) usually respond to conventional antiarrhythmic regimes
      of treatment. Rarely, the VA may prove intractable to therapy. This report is of
      three patients who presented at varying time frames (3 h to 10 weeks) following
      an anterior MI. They exhibited sustained monomorphic ventricular tachycardia and
      hemodynamic instability despite multiple antiarrhythmic drug therapy, intravenous
      magnesium, direct-current cardioversion (DCCV), overdrive pacing (in one case),
      and intra-aortic balloon counterpulsation (IABP). Although there was no clinical
      evidence of continuing ischemia and although coronary angiography that was done
      in each case showed the infarct-related artery (IRA) to subtend akinetic areas on
      left ventricular (LV) angiogram, percutaneous transluminal coronary angioplasty
      (PTCA) of the IRA was done in all three cases. Reestablishing patency of the IRA
      helped in controlling the VA dramatically with average therapeutic doses of
      antiarrhythmic drugs. All three patients showed this control to have been
      maintained over a follow-up period of more than 1 year, with partial improvement
      in LV function and signal-averaged electrocardiogram negative for late
      potentials. Thus, in patients with extensive infarction and intractable VA, PTCA
      of the IRA may provide control of VA even in the absence of clinical signs of
      active ischemia or viable muscle mass.

PMID- 7586772
TI  - Joint symptoms in relapsing polychondritis.
AB  - OBJECTIVE: To study articular symptoms in relapsing polychondritis (RP) and their
      relationship to other clinical manifestations and prognosis. METHODS: Fourteen
      patients who met the diagnostic criteria proposed by Damiani and Levine for RP
      were studied. Clinical symptoms were recorded and laboratory and radiologic
      examinations were carried out. In one patient a synovial histology was obtained.
      RESULTS: Twelve patients had joint symptoms affecting the peripheral joints (9),
      the chondrocostal junctions (5), or both sites together (2). Peripheral arthritis
      was the most frequent finding, affecting 6 patients, while peripheral arthralgia
      was the only articular manifestation in 3 patients. The development of joint
      symptoms (arthralgia, arthritis and costochondritis) was unrelated to the
      appearance of chondritis at other sites and no correlation was found between
      articular involvement and age at onset, duration of the disease, number of
      flares, or severity of the disease, either in terms of the number of organs
      involved or fatal outcome (p > 0.05). However, when articular symptoms were
      analysed separately arthritis was associated with a longer duration (50 months vs
      30), more affected organs (4.5 vs 3.3) and a poorer prognosis compared with
      patients with arthralgias alone or chondrocostal symptoms. CONCLUSION: Articular
      symptoms are common in RP but the presence of peripheral arthritis is associated
      with widespread disease and a poorer prognosis.

PMID- 7586774
TI  - A modified version of the Health Assessment Questionnaire (HAQ) for psoriatic
      arthritis.
AB  - OBJECTIVE: The purpose of the present investigation was to explore a modification
      of the Health Assessment Questionnaire (HAQ) to capture the functional problems
      associated with psoriasis as well as inflammatory arthritis in patients with
      psoriatic arthritis (PsA). METHODS: During a visit to the Psoriatic Arthritis
      Clinic, 118 patients with PsA were asked to complete the modified version of the
      HAQ. The original HAQ and expanded HAQ (HAQ-SK) scores were calculated.
      Correlation and regression analyses were used to examine the relationship between
      the severity of psoriasis and the functional status as measured by the various
      HAQ measures. RESULTS: The mean global HAQ score was 0.55 on a scale ranging from
      0 to 3, while the mean global HAQ-SK score was 0.56, suggesting that the
      modification, which involved adding items to reflect those aspects of physical
      functioning most affected by psoriasis, did not materially change the global HAQ
      score. There were no significant associations between the global HAQ-SK
      disability score or the added psoriasis items and the severity and activity of
      psoriasis, as measured by the Psoriasis Area and Severity Index (PASI) (all
      correlations < 0.20). The only significant association was found between the
      patient and the clinician ratings of psoriasis severity (r = 0.49). Open-ended
      questions suggest that psychosocial functioning is another dimension of health
      status which is of concern to PsA patients. CONCLUSION: The findings suggest that
      physical disabilities associated with the severity and activity of psoriasis are
      not captured by the HAQ or the HAQ-SK. Psychosocial functioning, an additional
      area of concern to PsA patients, is also not directly linked to physical
      functioning or to the severity of psoriasis.

PMID- 7586773
TI  - The levels of collagenase, tissue inhibitor of metalloproteinases-1 (TIMP-1),
      collagenase approximately TIMP-1 complexes and glycosaminoglycan (GAG) in
      sequential samples of synovial fluid aspirated from patients with osteoarthritis.
AB  - OBJECTIVE: Collagen turnover in connective tissues is thought to be controlled by
      the balance between the levels of interstitial collagenase and tissue inhibitor
      of metalloproteinases (TIMP-1). The aim of this study was to measure the level of
      total collagenase (MMP-1), TIMP-1, collagenase approximately TIMP-1 complex and
      glycosaminoglycan (GAG) in sequential samples of osteoarthritic knee synovial
      fluid from well documented patients to determine if these parameters changed with
      time and correlated with clinical indices. METHODS: Twenty-one patients were
      recruited and randomly allocated to receive tiaprofenic acid, indomethacin or
      naproxen. Total collagenase, TIMP-1, collagenase approximately TIMP-1 complex and
      GAG were measured in 80 osteoarthritic synovial fluids taken over a period of six
      months. RESULTS: The majority of fluids contained a molar excess of TIMP-1 over
      collagenase, although in seven fluids collagenase was present in excess; six of
      these samples were from a single patient. GAG levels were relatively unchanged
      over the six months studied. CONCLUSION: The levels of collagenase and TIMP-1
      varied between patients and over time in individual patients. No collagenase
      approximately TIMP-1 complex was found in any fluid. There was no significant
      difference in the median levels of collagenase, TIMP-1 or GAG in the different
      treatment groups. High levels of collagenase were found in one patient with a
      crystal related disease. These immunoassays give valuable information on the
      levels of collagenase and TIMP-1 in individual patients with time and may help to
      determine the mechanisms controlling the turnover of cartilage collagen in
      different arthritides.

PMID- 7586775
TI  - Serum erythropoietin and transferrin receptor levels in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is generally associated with mild anaemia.
      The role of erythropoietin (EPO) in the pathogenesis of this anaemia of chronic
      disorders is still a matter of controversy. Therefore, in a multicenter study we
      investigated the serum EPO concentration in 124 patients with rheumatoid
      arthritis. METHODS: Patients with uncomplicated iron deficiency and haemolytic
      anaemia served as the reference group (n = 54). The measurements were performed
      with a specific and sensitive ELISA: RESULTS: The mean EPO concentration +/- SD
      of the whole RA group (32.3 +/- 22.2 mU/ml) was elevated above normal. About 40%
      of the patients had underlying iron deficiency (defined by ferritin values < or =
      60 ng/ml) and a significantly higher median EPO concentration than patients with
      normal iron stores (35.8 mU/ml versus 20.7 mU/ml; p < 0.001). The iron deficiency
      was associated with lower disease activity, as defined by the C reactive protein.
      In contrast to the reference group (r = -0.78), there was no significant
      correlation between EPO and the haematocrit in either RA subgroup, although the
      values for the RA patients were within the 95% prediction range of the reference
      group. In addition to the EPO, we investigated the soluble transferrin receptor
      level as a measure of bone marrow erythropoiesis. The level in iron-replete RA
      subjects was about 1.6 times higher than in normal persons, reflecting a
      relatively hypoproliferative erythropoietic activity. CONCLUSION: This study
      shows that the EPO concentrations in RA are elevated above normal but lower than
      expected, and that the normal relationship between EPO and the degree of anaemia
      is impaired.

PMID- 7586776
TI  - Manifestations of Chlamydia induced arthritis in patients with silent versus
      symptomatic urogenital chlamydial infection.
AB  - OBJECTIVES: To evaluate whether Chlamydia-infected patients with and without
      urogenital symptoms have similar rheumatological manifestations or whether they
      belong to distinct clinical groups. METHODS: In a university-based study, we
      examined patients with unexplained arthritis in whom other rheumatic diseases had
      been excluded for urogenital chlamydial infection, and we investigated the
      clinical and radiological manifestations of the Chlamydia-positive patients.
      RESULTS: Sixty of 283 patients (21%) with unexplained arthritis had urogenital
      chlamydial infection. The infection was asymptomatic in 30%. There was no
      difference in the pattern of arthritis or immunological and serological
      characteristics in the patients with and without symptoms of urogenital
      infection, respectively. CONCLUSION: The pattern of Chlamydia-induced arthritis
      is similar in patients with or without symptoms of urogenital chlamydial
      infection. To recognize CIA, it may be helpful to examine patients with
      unexplained arthritis for Chlamydia even though they do not have symptoms of
      urogenital infection.

PMID- 7586777
TI  - Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose
      methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients.
AB  - OBJECTIVE: To compare folic acid (FA) levels in patients being treated with
      methotrexate (MTX) with those of untreated patients in order to investigate
      potential folate depletion by MTX and its possible relationship to the drug's
      efficacy. METHODS: In 33 patients on low-dose MTX therapy and in 24 controls, FA
      and cyanocobalamin (B12) levels were determined in serum and red blood cells
      (RBC). In addition, MTX levels in the RBC and serum were measured, and clinical
      and laboratory measures of disease activity were evaluated. RESULTS: MTX treated
      patients had lower FA levels than controls (median 4.36 vs 7.37 ng/ml, p <
      0.001). A significant correlation between serum FA and MTX/RBC (p < 0.01) and
      between the weekly dose and MTX/RBC (p < 0.01) was seen. There was apparently no
      correlation between FA and the cumulative total MTX. MTX patients had lower
      B12/RBC levels than the controls (p < 0.001); the serum levels of B12 were not
      different. Clinical features, ESR and CRP did not correlate with FA, B12 or MTX
      levels. CONCLUSIONS: The degree of folate depletion during MTX therapy depends
      primarily upon the weekly administered dose. Folate depletion may be related to
      B12 deficiency in RBC. Since FA levels were not related to parameters of disease
      activity it is conceivable that MTX does not exert its action in RA primarily by
      inhibiting dihydrofolatereductase. Therefore, additional folate compounds, if
      necessary, should not lead to a reduction in the efficacy of MTX.

PMID- 7586778
TI  - Correlation between methotrexate pharmacokinetic parameters, and clinical and
      biological status in rheumatoid arthritis patients.
AB  - OBJECTIVE: To determine the correlation between the pharmacokinetic (PK)
      parameters of methotrexate (MTX), clinical status and laboratory test results in
      rheumatoid arthritis (RA) patients. METHODS: 22 patients (4 M/18F, mean age: 50
      +/- 12 years, mean duration of RA: 8.5 +/- 6.5 years, mean duration on MTX: 8 +/-
      10 months) were included in a prospective study. The mean dose of MTX
      administered was 6 +/- 0.7 mg/m2 of body area/week. No patient received any
      nonsteroidal antiinflammatory drug (NSAID). Blood and urine samples were
      collected over 24 hours (9 blood samples). The MTX concentrations were assayed by
      fluorescence polarization immunoassay. Clinical parameters (Ritchie articular
      index, morning stiffness, joint pain count, joint swelling count), hematological,
      liver and renal function tests, and ESR were recorded. Correlations between the
      patients' PK parameters, laboratory tests and clinical status were carried out
      using Pearson's correlation coefficient test. RESULTS: A significant correlation
      was observed between the Ritchie articular index, morning stiffness and the area
      under the curve (p = 0.009 and p = 0.026, respectively). No correlation was found
      with the other parameters. CONCLUSION: These results suggest that when the
      patient's disease activity is higher, the AUC becomes more important, reflecting
      a greater body exposure to MTX.

PMID- 7586779
TI  - Quality of life in rheumatoid arthritis: a case-control study in patients living
      in northern Norway.
AB  - OBJECTIVE: To study quality of life parameters in patients with rheumatoid
      arthritis and the possible association of these parameters with disease activity.
      METHODS: Fifty-two women with rheumatoid arthritis and 52 controls completed two
      self reporting psychiatric screening tests: the General Health Questionnaire (GHQ
      - 30) and the Cantril Ladder scale. The number of psychiatric cases detected was
      not significantly higher for either group using the GHQ score S+ as the
      criterion. RESULTS: Comparing the GHQ scores, patients showed a higher score
      compared with the controls (p = 0.02). The patients scored significantly higher
      on feelings of incompetance (p = 0.004), but not on the other subgroups of
      psychiatric factors. The patients reported lower life satisfaction on the Cantril
      self anchoring ladder (p = 0.0001). The functional capacity score was positively
      associated with the GHQ score. No association was detected between disease
      duration or the other disease activity parameters and either the GHQ score or the
      life satisfaction score. CONCLUSION: This inconsistant relationship between
      clinical parameters and quality of life scores may be due to the fact that RA
      patients suffer from a chronic disease, or it may reflect an impaired
      psychosocial status in the patients. This study demonstrates that the increased
      psychological disturbances in women with RA is mainly explained by feelings of
      incompetance.

PMID- 7586780
TI  - Pain and fatigue induced by exercise in fibromyalgia patients and sedentary
      healthy subjects.
AB  - OBJECTIVE: To examine whether general feelings of fatigue, exercise-induced pain
      in the extremities, and exertion were different in female patients with
      fibromyalgia syndrome (FS) compared with sedentary healthy women. METHODS: Thirty
      seven FS patients and 20 healthy subjects were studied. Cardiovascular fitness
      was assessed by Aastrand's indirect, submaximal method. The period of repetitive
      dynamic muscle contractions and sustained static muscle contraction were
      measured. General feelings of fatigue before exercise and exercise-induced
      extremity pain were assessed by visual analogue scales. Exercise-induced exertion
      was recorded by Borg's Rating Scale of Perceived Exertion. RESULTS: No
      significant group difference in cardiovascular fitness was found (p = 0.8). In
      the FS patients general fatigue was (median 95% confidence interval) 69 (59 - 75)
      versus 32 (22 - 47) for the healthy controls (p < 0.0001). At the moment of
      interrupting the bicycle test, the perceived exertion score was 17 (16 - 18)
      among patients versus 13 (13 - 15) among controls (p < 0.0001). Compared with the
      controls, high exercise-induced extremity pain was found after sustained static
      and repetitive dynamic muscle contractions in the FS patients (p < 0.004), and 24
      hours later the patients' pain intensities had not returned to pre-exercise
      values (p < 0.01). CONCLUSION: High general fatigue, exercise-induced extremity
      pain, exertion and 24 hours post-exercise extremity pain in FS patients compared
      with healthy controls could not be explained by any group difference in
      cardiovascular fitness.

PMID- 7586782
TI  - Antiphospholipid syndrome in patients with cyanotic congenital heart disease.
AB  - Patients with cyanotic congenital heart disease exhibit an increased incidence of
      thrombotic episodes and are frequently thrombocytopenic. We studied the sera of
      15 patients with this type of heart malformation, searching for anticardiolipin
      antibodies. 3/15 had positive results. The three of them were adult females; two
      had thrombotic episodes and a false positive VDRL. Thus, cyanotic congenital
      heart disease may be another disease entity associated with the antiphospholipid
      syndrome.

PMID- 7586783
TI  - Inefficacy of azapropazone in the acute arthritis of Behcet's syndrome: a
      randomized, double blind, placebo controlled study.
AB  - Sixty-three consecutive Behcet's syndrome patients with an acute arthritis of up
      to 10 days duration were treated either with azapropazone (APZ) 300 mg t.i.d. or
      placebo for three weeks. Twenty-eight patients (14 males, 14 females: mean age
      36.2 +/- 8.1 SD years) from the APZ group and 29 patients (18 males, 11 females;
      mean age 34.2 +/- 8.4 SD years) from the placebo group completed the trial. At
      the end of the trial the arthritis persisted in 53.5% (15/28) of the APZ patients
      and in 41.3% (12/29) of the placebo patients (chi 2 = 0.85; NS). Six patients
      (6/28; 21%) from the APZ group and 9 patients (9/29; 31%) from the placebo group
      developed new joint involvement (chi 2 = 0.7; NS). There was no difference in the
      duration of arthritis between the two groups (19.9 +/- 8.3 SD days in the APZ
      groups vs. 19.7 +/- 8.2 SD days in the placebo group; NS). The degree of joint
      swelling, the tender joint score and the visual analogue score for pain
      significantly improved in both groups, but there was no difference in any of
      these parameters between the groups except for a significant difference in the
      visual analogue score for less pain at the first week in the azapropazone group
      (t = 2.23; p < 0.05). There were also no differences in the mean numbers of
      acetaminophen tablets used or in the CRP and ESR levels between the two groups.
      We conclude that azapropazone is not effective in controlling the arthritis of
      Behcet's syndrome.

PMID- 7586781
TI  - D-penicillamine-induced autoantibodies in a mouse model.
AB  - OBJECTIVE: We have previously shown that the administration of D-penicillamine (D
      PEN) to patients with rheumatoid arthritis induces circulating insulin
      autoantibodies (INSAAB). In order to gain further insight into such immune
      responses, we measured a battery of circulating autoantibodies in 4 strains of
      mice receiving D-PEN: C57BL/KsJ, BALB/c, C3H/HeJ, and C57BL/6. These rodents
      groups differ in their degree of susceptibility to streptozotocin (STZ)-induced
      immune diabetes (SIMD), which is high in the first 2 strains, and mild and nil in
      the third and fourth, respectively. METHODS: Randomly assigned animals from each
      group were given a weekly subcutaneous (SC) injection of either D-PEN 1 mg, D-PEN
      3 mg, or solvent (PBS) for a period of 4 weeks. Serum levels of antibodies to
      insulin, single stranded DNA (ssDNA), thyroglobulin, and cardiolipin were
      measured weekly. RESULTS: Only the C57BL/KsJ and C3H/HeJ mice reacted to D-PEN
      administration. When compared to the pre-treated and solvent-treated mice, D-PEN
      1 mg, and to a lesser degree D-PEN 3 mg, induced elevation of antibodies to
      insulin and to ssDNA in C57/KsJ mice (p < 0.001), while only ssDNA antibodies
      were detected in the C3H/HeJ mice (p < 0.0001 for D-PEN 1 mg; p < 0.05 for D-PEN
      3 mg). D-PEN had no effect on the level of antibodies to cardiolipin or to
      thyroglobulin in any of the mice. CONCLUSIONS: This study showed that D-PEN
      induces an antigen(s)-specific humoral response only in mice already inherently
      prone to autoimmunity. This model suggests that the activation of autoimmunity by
      environmental factors is probably facilitated by genetic background, and might
      partly explain the diversity of autoimmune manifestations in D-PEN-treated
      patients.

PMID- 7586784
TI  - Primary Sjogren's syndrome and primary biliary cirrhosis: differences and
      similarities in the autoantibody profile.
AB  - Sera from 61 patients with primary biliary cirrhosis (PBC) and 23 patients with
      primary Sjogren's syndrome (pSS) were tested for the presence of autoantibodies
      to 15 different antigens (PDH, RNP, SS-A, SS-B, Sm, Scl-70, H2AH2B, Jo-1,
      collagen-type I, GBM, GM <--> 1, Sulf, GD1b, MPO, PR3). Patients with pSS had
      significantly (p < 0.01) higher frequencies of antibodies to SS-A, SS-B and RNP
      (78%, 52%, 22% vs 29%, 20%, 5%, respectively) when compared to patients with PBC.
      On the other hand, patients with PBC had significantly (p < 0.01) higher
      frequencies of antibodies to PDH, Sm, Jo-1, collagen and MPO (80%, 34%, 26%, 52%,
      67% vs 13%, 9%, 13%, 13%, 9%, respectively) as compared with patients with pSS.
      For all the other autoantibodies, no significant differences were found between
      PBS and pSS patients. These data on the similarities in autoimmunity between two
      diseases with different clinical presentations shed more light on the mosaic of
      autoimmunity.

PMID- 7586785
TI  - Graves' ophthalmopathy and relapsing polychondritis.
AB  - A case of Graves' ophthalmopathy and relapsing polychondritis is reported. The
      eye condition responded to Cyclosporin A. The association of the two conditions
      is discussed.

PMID- 7586786
TI  - Churg-Strauss syndrome presenting as polymyositis.
AB  - Churg-Strauss syndrome is a vasculitis-based pathology, predominantly
      characterized by asthma and eosinophilia. Histopathologically, the vessel wall
      infiltration contains a substantial proportion of eosinophils and extravascular
      granulomata can be demonstrated. We report a case of Churg-Strauss syndrome
      presenting as polymyositis.

PMID- 7586788
TI  - Asplenia in systemic lupus erythematosus: a simple coincidence?
AB  - Two patients with asplenia and systemic lupus erythematosus are described. Both
      patients presented with unusual symptoms of the disease. The possible association
      of asplenia, presumably congenital, and systemic lupus erythematosus is
      discussed.

PMID- 7586789
TI  - Synovium and epithelia: barriers between self and non-self?

PMID- 7586787
TI  - Glomerulonephritis leading to end stage renal disease in a patient with primary
      Sjogren syndrome.
AB  - Renal disease as the sole manifestation of extra-glandular involvement is rare in
      primary Sjogren's syndrome. We report a case of membranous nephritis presenting
      with proliferative changes including crescents, which led to renal insufficiency
      in a patient with primary Sjogren's syndrome. The renal involvement was not
      associated with cryoglobulinemia.

PMID- 7586790
TI  - Skin rash and anti-Ro/SS-A antibodies in an infant from a mother with silicone
      breast implants.
AB  - An infant with erythematous rash born from a mother with silicone breast implants
      is described. The diagnosis of possible neonatal lupus was suggested based on the
      presence of the skin rash and positive Ro/SS-A antibodies in the infant and
      positive ANA and Ro/SS-A in the mother.

PMID- 7586792
TI  - Antiperinuclear factor isotypes in rheumatoid arthritis.

PMID- 7586793
TI  - Antiperinuclear factor isotypes in rheumatoid arthritis.

PMID- 7586791
TI  - An unusual case of mixed sclerosing bone dystrophy presenting with morning
      stiffness and joint swelling in childhood: a case report.
AB  - We describe a case of a 16 year old native Indian girl with pain, morning
      stiffness and foot swelling who had radiographic changes consistent with mixed
      sclerosing bone dystrophy (MSBD) combined with fibrous dysplasia.

PMID- 7586794
TI  - Systemic vasculitis in juvenile dermatomyositis: a fatal case.

PMID- 7586795
TI  - Epileptic seizures as a neurological complication of Reiter's syndrome.

PMID- 7586798
TI  - Influence of rifampicin on hydroxychloroquine.

PMID- 7586796
TI  - Ipsilateral sternocostal arthro-osteitis and palmar pustulosis.

PMID- 7586797
TI  - The volume of synovial fluid effusion in psoriatic arthritis.

PMID- 7586800
TI  - Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor
      of bone.
AB  - Basement membrane forms widespread barriers to tumor invasion. It has been shown
      that tumor-secreted, basement membrane-degrading enzymes, namely
      metalloproteinases (MMPs) play an important role in tumor invasion and
      metastasis. In this study, we determined the enzymatic activity, content, and
      mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of
      human giant-cell tumor of bone (GCT) in vitro and in tissue extracts (in vivo).
      Gelatin zymography showed the presence of lytic bands at M(r) 121,000, 92,000,
      and 72,000, and these enzymatic activities were inhibited by EDTA, an inhibitor
      of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the
      presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late
      passage showed only MMP-2. Northern blots using labeled cDNA probes specific for
      these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb
      transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV
      collagenases, we studied their cellular distribution by immunohistochemical
      means. Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72
      kDa type IV collagenase in the giant cells. It appears, therefore, that MMP-9 may
      play an important role in the malignant behavior of GCTs and suggests a potential
      therapeutic role for protease inhibitors in attempting to minimize the invasive
      behavior of GCTs.

PMID- 7586799
TI  - In vitro invasiveness of DU-145 human prostate carcinoma cells is modulated by
      EGF receptor-mediated signals.
AB  - Prostate carcinomas often present an autocrine stimulatory loop in which the
      transformed cells both express the EGF receptor (EGFR) and produce activating
      ligands (TGF alpha and EGF forms). Up-regulated EGFR signalling has been
      correlated with tumor progression in other human neoplasia; however, the cell
      behaviour which is promoted remains undefined. To determine whether an EGFR
      induced response contributes to cell invasiveness, we transduced DU-145 human
      prostate carcinoma cells with either a full-length (WT) or a mitogenically-active
      but motility-deficient truncated (c'973) EGFR. The DU-145 Parental and two
      transgene sublines all produced EGFR and TGF alpha, but the transduced WT and
      c'973 EGFR underwent autocrine downregulation to a lesser degree, with more
      receptor remaining intact. DU-145 cells transduced with WT EGFR transmigrated a
      human amniotic basement membrane matrix (Amgel) to a greater extent than did
      Parental DU-145 cells (175 +/- 22%). Cells expressing the c'973 EGFR invaded
      through the Amgel only to about two thirds the extent of the Parental cells (62
      +/- 23%). A monoclonal antibody which prevents ligand-induced activation of EGFR
      decreased the invasiveness of WT-expressing cells by half and Parental cells by a
      fifth, but had little effect on the invasiveness of c'973-expressing cells; with
      the result that in the presence of antibody, all three cell lines transmigrated
      the Amgel to the same extent. The different levels of invasiveness between the
      three sublines were independent of cell proliferation. These findings
      demonstrated that EGFR-mediated signals increase tumor cell invasiveness and
      suggested that domains in the carboxy-terminus are required to signal
      invasiveness. As an initial investigation into the mechanisms underlying the EGFR
      mediated enhanced invasiveness, we determined whether these cells presented
      different collagenolytic activity, as the major constituents of Amgel are
      collagen types I and IV. All three sublines secreted easily detectable levels of
      gelatin-directed proteases and TIMP-1, with WT cells secreting equivalent or
      lower levels of proteases. The proteolytic balance in these cells did not
      correlate with invasiveness. These data suggest that the TGF alpha-EGFR autocrine
      loop promotes invasiveness and that this is accomplished by signalling cell
      properties other than differential secretion of collagenolytic activity.

PMID- 7586802
TI  - Clonal heterogeneity in plasminogen activator activity produced by two murine
      tumor cell lines.
AB  - Secretion of plasminogen activators (PA) has been shown to be an important method
      by which cells can initiate degradation of the extracellular matrix (ECM). In
      this study we have examined the PA production of two murine cell lines, KHT-LP1,
      a fibrosarcoma and SCC-VII, a squamous cell carcinoma, and have found a high
      degree of clonal heterogeneity. Our method for assaying PA activity measures the
      PA activity of small colonies of cells derived from single cells, using an in
      vitro fibrin/agarose PA assay in which colonies with PA activity form discernable
      'halos' in the fibrin/agarose semisolid growth medium. When these small colonies
      of cells were disassociated and the component cells were reassayed for PA
      activity it was again found to be heterogeneous, suggesting that this property
      can be generated during the growth of the colonies. KHT-LP1 cells derived from
      single cell clones were assayed for PA activity to determine the rate at which
      this phenotype was produced. It was found that the rate of formation of the PA
      activity phenotype was 6.5 x 10(-6) events per cell generation. The component
      cells of colonies which initially demonstrated high PA activity produced more PA
      activity than the component cells of the colonies that had low PA activity. This
      suggests that some aspects of the phenotype may be more stable than others. To
      examine whether the addition of lethally irradiated cells could stabilize the
      phenotype we determined whether fibrin/agarose PA assays supplemented with
      lethally irradiated cells would reduce the heterogeneity of PA activity. The
      results indicated that the heterogeneity was not reduced, and there was an
      increase in the average amount of PA activity.

PMID- 7586804
TI  - The establishment of two cell lines from a mouse uterine cervical carcinoma (U14)
      and their metastatic phenotype changes.
AB  - This paper studies the heterogeneity of metastatic potential of murine cervical
      carcinoma (U14). Two cell lines, P11-90 and L10-90, were established from a
      pulmonary metastatic substrain (U14AP11) and a lymphatic metastatic substrain
      (U14AL10), which were selected from U14 in vivo after 11 and 10 passages,
      respectively. The biologic differences between the two cell lines are as follows.
      (1) The cells of the P11-90 line grow more rapidly compared with the L10-90 line.
      From the 40th passage the medium pH was different. (2) The median number of
      chromosomes in P11-90 and L10-90 was 72 and 64, respectively; the rates of gap
      aberration were 88% and 78%, respectively. (3) The number of T lymphocytes and T
      helper lymphocytes in the peripheral blood from hosts with P11-90 were higher
      than that of hosts transplanted with L10-90, but the number of B lymphocytes in
      the latter was larger than that in the former. (4) The metastatic potential of
      each cell line partially decreased compared to the relative tumor substrain, but
      their organ preference still remained and the transplant locations, axillary or
      footpad, had a prominent influence on their metastatic behavior. To observe the
      effects of metastatic target organs on the metastatic phenotypes of tumor cells,
      as well as to explore a method for the establishment and maintenance of the
      metastatic organ preference of tumor cells, conditioned medium (CM) from
      pulmonary or lymphatic node diploid cells was added to the culture medium of P11
      90 and L10-90. Two sublines, P + P11-90 and Ln + L10-90, were thus established.
      Using stereological methods we found that the majority of P + P11-90 cells became
      larger and their nuclei also increased in size compared with their parental
      lines, but the majority of Ln + L10-90 cells became smaller in size, though the
      nuclei were enlarged. The pulmonary metastatic rate and lymphatic metastatic rate
      of P + P11-90, as well as the lymphatic metastatic rate of Ln + L10-90, were
      restored dramatically. The results suggest that by taking advantage of the
      interaction between tumor cells and the CM of host cells the metastatic potential
      of tumor cell lines can be maintained in vitro. Our work may offer an
      experimental model for the manipulation of metastasis of cell lines coming from
      the same parent strain but with different metastatic potentials.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7586801
TI  - Integrin-mediated entry into S phase of human gastric adenocarcinoma cells.
AB  - The integrins are a family of integral membrane receptors that participate in
      binding to various extracellular and cell surface proteins during adhesion,
      migration, and homing of normal and neoplastic cells. In this study, we
      characterized the involvement of integrins in mediating the growth of an adhesion
      dependent gastric adenocarcinoma line, ST2. This line was distinguished and
      selected for study based on its inability to grow when suspended in soft agar or
      plated on poly(2-hydroxyethyl methacrylate)-coated dishes. ST2 cells arrested in
      G0/G1 of the cell cycle when deprived of adhesion to substrate. Using purified
      matrix components, collagen was found to be highly active in promoting beta 1
      integrin-mediated cell attachment and spreading. Subsequent to spreading on
      collagen, the cells were released from G0/G1 block and progressed into S phase.
      Monoclonal antibodies to alpha 2 or beta 1 integrin blocked the reinduction of
      both cell spreading and entry into S phase. These studies suggest that during the
      metastatic process, integrin receptor interaction with the insoluble matrix may
      be an important step leading to proliferation of some tumors.

PMID- 7586803
TI  - Osteopontin (OPN) may facilitate metastasis by protecting cells from macrophage
      NO-mediated cytotoxicity: evidence from cell lines down-regulated for OPN
      expression by a targeted ribozyme.
AB  - Osteopontin (OPN) is a GRGDS-containing phosphoglycoprotein that is capable of
      facilitating cell adhesion and modulating gene expression via integrin receptors.
      Three hammerhead ribozymes designed to target three different regions of OPN mRNA
      were shown to cleave the message catalytically in vitro. Plasmid vectors that had
      been engineered to express the ribozymes in mammalian cells were used to generate
      stably transfected T24 H-ras-transformed NIH3T3 cells that normally express OPN
      at high levels. Northern and Western blot analyses showed that OPN mRNA and
      protein expression were reduced in a subset of these anti-OPN ribozyme-expressing
      cell lines. Cells whose ability to produce OPN had been impaired exhibited
      greater sensitivity to the cytotoxic action of activated RAW264.7 macrophage-like
      cells; they were also less effective at suppressing macrophage NO production. In
      agreement with previous reports, they were also less tumorigenic and metastatic
      in an experimental metastasis assay. These results are consistent with the
      hypothesis that OPN serves as a defense against NO-mediated host cell
      cytotoxicity and thereby augments the metastatic phenotype.

PMID- 7586805
TI  - Detection of candidates for cancer cell motility inhibitory protein in the
      Dunning adenocarcinoma model.
AB  - The more differentiated components of a primary tumor may produce substances that
      reduce the growth rate and metastatic potential of more aggressive components. In
      the Dunning R-3327 prostatic adenocarcinoma model, cancer cell motility is
      required for metastatic potential. Medium conditioned by the non-motile, non
      metastatic G subline contains proteins of molecular weight 50-100 kDa that
      inhibited the motility of the highly motile, highly metastatic MAT-LyLu subline.
      G subline-conditioned medium was separated by DEAE-cellulose chromatography using
      a linear gradient of 0-0.5 M NaCl in 100 mM Tris at pH 8.3. The motility
      inhibitory activity of G-conditioned medium was localized to column fractions 51
      70 that contained 18% of the applied protein and only 6.5% of the proteins
      secreted by the G cells. Analysis of pooled fractions 51-60 and 61-70 by two
      dimensional gel electrophoresis identified five protein families, with a total of
      12 charged proteins of molecular weights approximating 66, 54, 50, 41 and 34 kDa,
      that were not present or present in reduced quantities in column fractions that
      did not inhibit motility. Isolation and identification of motility inhibitory
      protein may prove it the first substance discovered that is produced by a more
      differentiated component of a neoplasm that directly inhibits a metastasis
      associated property.

PMID- 7586808
TI  - Ultrastructural study of TPA-induced cell motility: human well-differentiated
      rectal adenocarcinoma cells move as coherent sheets via localized modulation of
      cell-cell adhesion.
AB  - We previously found that 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced
      invasion of Matrigel was associated with augmentation of cell motility but not
      with metalloproteinase activity in a highly metastatic variant (L-10) of human
      rectal adenocarcinoma cell line RCM-1. In a two-dimensional cell motility assay,
      TPA induced active L-10 cell locomotion with characteristic morphology; the cells
      moved outwards from the cell islands mainly as a localized coherent sheet of
      cells. The leading cells showed locomotor morphologies with fan-shaped leading
      lamellae while the following cells had cell contacts on all sides and appeared to
      lack leading lamellae. In the present ultrastructural study, the following cells
      frequently showed tapering cytoplasmic protrusions and leading lamella-like
      processes underlapping a preceding cell, indicating that the locomotion mechanism
      is almost the same for both the leading and following cells. For this type of
      locomotion as a coherent sheet we propose that localized modulation of cell-cell
      adhesion was induced such that wide intercellular gaps occurred at the lower
      portion of the cells to allow the cells to extend the tapering cytoplasmic
      processes and leading lamellae while close cell-cell contacts remained at the
      upper portion of the cells. These TPA-induced changes took place predominantly in
      the cells at the periphery of the cell islands, while the cells in the middle of
      the cell islands maintained close cell-cell contacts including complex
      interdigitation all around the cells, suggesting the modulation of TPA action by
      cell-cell interaction. Additionally, consistent with the evidence for junctional
      complexes between the cells moving outwards, the Lucifer-yellow dye transfer
      studies showed some, limited cell-cell coupling, suggesting the presence of at
      least some gap junctional intercellular communication in the moving cell sheets.

PMID- 7586807
TI  - Increase of a urokinase receptor-related low-molecular-weight molecule in
      colorectal adenocarcinomas.
AB  - Proteolytic activity is important for tumor growth and metastasis. Plasminogen
      and urokinase-type plasminogen activator (u-PA) constitute one of the most
      extensively studied proteolytic systems believed to participate in these
      processes. u-PA cleaves plasminogen to plasmin, which in turn degrades
      surrounding extracellular matrix and allows tumor cells to migrate to other
      areas. The specific receptor for u-PA (u-PAR) has also been implicated as an
      essential modulator in this pathway. Eleven paired samples of colorectal cancers
      and normal mucosal tissues from the same patients were removed at surgery. The
      tissues were homogenized and the supernatants assayed for u-PAR immunoreactivity,
      u-PAR antigen concentration, u-PAR binding activity and u-PA activity. Immunoblot
      analysis showed that a major u-PAR species of approximately 55 kDa was present in
      all tissues. In addition, a protein band of approximately 41 kDa, which
      crossreacted with anti-u-PAR antibodies, was also found in the tumors. This
      protein band was either absent, or present in relatively small amounts in the
      normal colorectal tissues. Cross-linking experiments showed that the
      approximately 55 kDa band only, and not the approximately 41 kDa band, was able
      to bind either single chain urokinase-type plasminogen activator (scu-PA) or the
      amino terminal fragment of urokinase (ATF). The tumor samples also exhibited
      highly elevated u-PA activity and u-PAR antigen relative to the corresponding
      normal tissues. Elevated u-PA activity appeared to correlate with elevated u-PAR
      antigen in colorectal cancers, but not in the normal tissues. These increases
      were also associated with increase of the u-PAR-related, low-molecular-weight
      protein in the tumor samples. The measurement of u-PAR and the u-PAR-related
      protein, in addition to u-PA activity, could have diagnostic or prognostic value
      in this type of cancer.

PMID- 7586809
TI  - 40th Annual meeting of the German Society for Neuropathology and Neuroanatomy.
      Tubingen, October 11-14, 1995. Abstracts.

PMID- 7586810
TI  - Clinical biocompatibility and degradation of polylevolactide screws in the ankle.
AB  - The clinical biocompatibility and degradation behavior of absorbable fracture
      fixation devices are still incompletely known in humans. Fifty-one patients with
      displaced fracture of the ankle treated by open reduction and internal fixation
      with absorbable screws made of polylevolactide were seen in followup for at least
      3 years. The mean duration of followup time was 52 months. The tissue tolerance
      and degradation of the devices were studied clinically and radiographically using
      computed tomographic scans. In addition, biopsy specimens for histologic
      examination were taken in 5 patients. The screws were clinically effective: An
      accurate position of the fragments was maintained until union in 50 patients. A
      mild transient subcutaneous late foreign body reaction occurred in 1 patient 22
      months after fixation of the fracture. Despite radiographic evidence of an
      advancing degradation of the implants, biopsy specimens taken 45 months after the
      original operation still showed consistent areas of polylactide in the tissues.
      In 3 patients, a disturbing palpable subcutaneous screw head had to be removed.
      The incidence of foreign body reactions to polylevolactide screws in the ankle
      seems to be low, but the duration of the degradation process of the polymer in
      human tissues is considerably longer than has been anticipated.

PMID- 7586811
TI  - Tactics and general principles in the treatment of polytraumatized disaster
      victims.
AB  - The authors reviewed their experiences of treating masses of victims after
      disasters in Arzamas, Armenia, and Ethiopia. To handle these vast numbers of
      victims, local hospitals were reorganized into specialized clinics with
      appropriate equipment and medical personnel. Some of the patients were evacuated
      to multispecialized clinics or rear hospitals. A complex of diagnostic and
      treatment modalities were used on these patients, including intrabone injections,
      immunoprophylaxis for purulent complications, skin and bone grafting and external
      fixation systems designed in Russia. The overwhelming majority of the patients
      was discharged with good results. To prevent common tactical, treatment, and
      surgical mistakes, it is necessary to improve medical education to train
      multispecialized teams in disaster medicine prepared to work under extreme
      conditions.

PMID- 7586812
TI  - Arthroscopic ankle arthrodesis in rheumatoid arthritis.
AB  - Several techniques for ankle arthrodesis have been described. Many of them are
      not suitable in patients with severe rheumatoid arthritis because of multiple
      joint involvement, osteoporosis, and increased risk of infection caused by poor
      skin conditions. The arthroscopic technique described in this article has been
      used in 7 patients with seropositive rheumatoid arthritis and 1 patient with
      seronegative rheumatoid arthritis (10 ankle joints; 2 patients surgically treated
      bilaterally). All patients successfully obtained ankle joint arthrodesis. The
      mean time to fusion was 10 weeks (range, 6-12 weeks). There was a 100% fusion
      rate without any complication.

PMID- 7586813
TI  - Peroneal nerve palsy and compartment syndrome in bilateral femoral fractures.
AB  - Four patients with bilateral femoral shaft fractures sustained 4 peroneal nerve
      palsies and 2 compartment syndromes during supine intramedullary nailings of
      their fractures. In each case, the compartment syndrome or common peroneal nerve
      palsy or both developed in the leg that was placed initially in the calf
      supported leg holder during intramedullary rodding of the contralateral femur.
      Three of 4 patients had near to full recovery of motor strength postoperatively.
      The authors recommend that a leg with a fractured femur not be positioned in a
      calf-supported leg holder.

PMID- 7586806
TI  - Integrin alpha 6 expression in human prostate carcinoma cells is associated with
      a migratory and invasive phenotype in vitro and in vivo.
AB  - Cell adhesion and migration are important features in tumor invasion, being
      mediated in part by integrins (extracellular matrix receptors). Integrins are
      significantly decreased in human prostate cancer. An exception is alpha 6
      integrin (laminin receptor) which persists during prostate tumor progression. We
      have selected high (DU-H) and low (DU-L) expressors of alpha 6 integrin from a
      human prostate tumor cell line, DU145, to assess experimentally the importance of
      alpha 6 integrin in tumor invasion. DU-H cells exhibited a four-fold increased
      expression of alpha 6 integrin on the surface compared to DU-L cells. Both cell
      types contained similar amounts of alpha 3 and alpha 5 integrin. The DU-H cells
      contained alpha 6 subunits complexed with both the beta 1 and beta 4 subunits
      whereas DU-L cells contained alpha 6 complexed only with beta 4. DU-H cells were
      three times more mobile on laminin as compared to DU-L, but adhered similarly on
      laminin. Adhesion and migration were inhibited with anti-alpha 6 antibody. Each
      subline was injected intraperitoneally into SCID mice to test its invasive
      potential. Results showed greater invasion of DU-H compared to DU-L cells, with
      increased expression of alpha 6 integrin on the tumor at the areas of invasion.
      These data suggest that alpha 6 integrin expression is advantageous for prostate
      tumor cell invasion.

PMID- 7586815
TI  - Posteromedial tibial plateau fractures. Operative treatment by posterior
      approach.
AB  - Seven patients treated by open reduction through a single posterior approach and
      internal fixation with an AO T-plate for displaced posteromedial fracture of the
      tibial plateau were reviewed. Followup ranged from 1 to 10 years, and all
      patients had excellent or good results, and there were no complications caused by
      the method of treatment.

PMID- 7586814
TI  - Nonreamed nailing of closed and minor open tibial fractures in patients with
      blunt polytrauma.
AB  - A retrospective comparison of dynamic and static locking mode nonreamed nails in
      88 closed, Grades I and II open tibial fractures is presented. Amount of time and
      number of reoperations required to unite fractures were compared for dynamic
      (Group 1, n = 31) and static locked (Group 2, n = 13) Winquist I and II
      fractures, and dynamic (Group 3, n = 14) and static locked (Group 4, n = 30)
      Winquist III, IV, and segmental fractures. Total reoperations also were compared;
      Tibias treated with dynamic nails united in an average of 20 weeks, with 3
      reoperations; tibias treated with static locked nails united in an average of 30
      weeks, with 21 reoperations. Group 1 fractures united in an average of 20 weeks,
      with 1 reoperation; Group 2 fractures united in an average of 32 weeks, with 4
      reoperations. Group 3 fractures united in an average of 20 weeks; Group 4
      fractures united in an average of 29 weeks, with 11 reoperations. In the group of
      tibias treated with dynamic nails, 3 additional operations were done; in the
      group of tibias treated with static locked nails, 7 additional operations were
      done. There was 1 infection and 3 deformities. Static locking mode appeared to
      delay union, especially when Groups 1 and 2 are compared; these fractures can be
      nailed without locking screws.

PMID- 7586816
TI  - Idiopathic spinal epidural lipomatosis. Case report and review of literature.
AB  - Idiopathic spinal epidural lipomatosis rarely is found (8 reported cases) in the
      absence of steroid treatment or obvious endocrinopathy. One additional
      symptomatic case with gait difficulty is described here. The only common
      etiologic factor for all cases is their obesity. Magnetic resonance imaging is
      the most helpful diagnostic means and should be used initially. In a patient with
      radicular pain or progressive paralysis who is obese, spinal epidural lipomatosis
      may be the etiologic factor involved.

PMID- 7586817
TI  - Lymphangiosarcoma following mastectomy.
AB  - This study reviews 16 cases of lymphangiosarcoma of the upper extremity after
      mastectomy for breast cancer (Stewart-Treves syndrome) was done at the author's
      institution from 1970 to 1992. Lymphangiosarcoma was diagnosed an average of 10.6
      years (range, 5.6-18 years) after the diagnosis of breast cancer. Presenting
      signs included a bruise (6 patients); increased swelling (4); a red, raised
      lesion (2); a palpable mass (2); a blister appearance (1); and a non-healing
      eschar with continual bleeding (1). After biopsy, surgical treatment included
      forequarter amputation (8 patients), wide excision with grafting (5), and above
      elbow amputation (1). Local recurrence of the lymphangiosarcoma occurred on the
      chest wall in 11 of the 16 patients after an average of 10.9 months. Metastasis
      occurred in 11 patients. (Metastasis occurred in 1 patient without local
      recurrence, and 1 patient with locally recurrent lymphangiosarcoma died of breast
      cancer before evidence of metastatic lymphangiosarcoma.) There are 2 long-term
      survivors who have lived 9.3 and 6 years, respectively, since the operation. One
      had been treated with a forequarter amputation and the other with wide excision.
      Early recognition and surgical treatment seem to offer the only chance for long
      term survival.

PMID- 7586819
TI  - The surgical anatomy of the radial nerve around the humerus.
AB  - Twenty-four cadaveric arms were dissected to determine the position of the radial
      nerve on the posterior aspect of the humerus relative to the posterior tip of the
      acromion, the medial and lateral epicondyles, the division between the lateral
      and long heads of the triceps, and the triceps aponeurosis. The radial nerve
      passed anterior to the long head of triceps and cross onto the posterior shaft of
      the humerus an average of 124 mm below the posterior tip of the acromion. It was
      never closer than 97 mm. The nerve usually lies on the medial head of the triceps
      as it courses posteriorly around the humerus and then leaves the posterior shaft
      of the humerus an average of 126 mm above the lateral epicondyle and 131 mm above
      the medial epicondyle. It was never within 100 mm of either epicondyle. The
      surgeon can use these landmarks as guidelines to avoid the radial nerve during
      operative intervention on the humerus.

PMID- 7586818
TI  - Desmoplastic fibroma. Aggressive curettage as a surgical alternative for
      treatment.
AB  - In this article, the authors present 5 patients with desmoplastic fibroma and
      review the literature. Four patients had aggressive curettage with bone graft,
      and 1 had aggressive curettage alone. Although the literature reports that many
      patients have recurrence after curettage, there have been no recurrences in these
      5 patients during followup periods ranging from 5 years 6 months to 9 years.
      Although wide excision has been recommended in the literature, treatment with
      aggressive curettage achieved clinical and radiographic control of the lesions
      for at least an intermediate duration of followup.

PMID- 7586820
TI  - Soft tissue attachments of the ulnar coronoid process. An anatomic study with
      radiographic correlation.
AB  - Regan and Morrey proposed a 3-type coronoid fracture classification observing
      that the incidence of concommitant elbow dislocation was proportional to fragment
      size. Elbow instability associated with coronoid fractures presumably is related
      to disrupted bony architecture and ineffective stabilizers attached to the free
      fragment. Twenty cadaveric elbows were dissected, measuring medial collateral
      ligament, anterior capsule, and brachialis muscle insertion loci on the coronoid.
      Radiographs were taken after radiopaque labeling of the stabilizer insertions.
      The anterior bundle of the medial collateral ligament insertion averaged 18.4 mm
      dorsal to the coronoid tip. Only in Type III fractures would it be attached to
      the free fragment. The capsule inserted an average of 6.4 mm distal to the
      coronoid tip. Rarely should Type I fractures result from a capsular avulsion,
      because only 3 of 20 specimens had the capsule inserting on the tip. The
      brachialis had a musculoaponeurotic insertion onto the elbow capsule, coronoid,
      and proximal ulna. The bony insertion averaged 26.3 mm in length, with its
      proximal margin averaging 11 mm distal to the coronoid tip. In only Type III
      fractures is the fragment large enough to include the brachialis bony insertion.

PMID- 7586821
TI  - Establishment and characterization of a human malignant fibrous histiocytoma cell
      line.
AB  - Malignant fibrous histiocytoma is the most frequent soft tissue sarcoma. However,
      the pathogenesis still remains unclear, because there are very few human
      malignant fibrous histiocytoma cell lines available for precise cellular study.
      In this study, a human malignant fibrous histiocytoma cell line (MMF-1) was
      established from the pulmonary metastatic lesion of a 55-year-old man with
      malignant fibrous histiocytoma. Human cell line MMF-1 and its heterotransplanted
      tumor had almost the same characteristics as the original tumor morphologically
      and immunohistochemically. This cell line is expected to be a useful for studying
      the pathogenesis of malignant fibrous histiocytoma. The cloned cell lines (MMF-2
      and MMF-3) also consisted of spindle-shaped, polygonal, and multinucleated giant
      cells, meaning that the fibroblast-like cells, histiocyte-like cells, and
      multinucleated giant cells seen in malignant fibrous histiocytoma were derived
      from a single tumor cell. Human cell line MMF-1 produced inflammatory cytokines,
      such as tumor necrosis factor-alpha, macrophage colony-stimulating factor,
      interleukin-8, and monocyte chemotactic and activating factor, that might be
      involved in the morphogenesis of malignant fibrous histiocytoma. Furthermore, the
      results of the analysis of human cell line MMF-1 suggested that malignant fibrous
      histiocytoma originated from a poorly differentiated fibroblast.

PMID- 7586822
TI  - General concepts of surgical treatment of severe multisystem injuries.
AB  - This article is based on an investigation of the management of 1976 patients with
      multisystem injuries. Three hundred twenty-five patients with multiple trauma and
      981 patients with single injury were studied. The surgical treatment of severe
      multisystem injuries is based on 3 main concepts. The first concept is the
      substantiated widening of the score of indications for surgical treatment of
      injuries. Surgical treatment is done in 68.9% of patients with multisystem
      injuries. Indications for surgical intervention (according to their significance)
      can be categorized as emergency, urgent, postponed, and planned operations; these
      were 59%, 17.2%, 23.5%, and 11.3%, respectively, of total surgical procedures.
      The second concept is assessment of the clinical state of injured patients by
      means of the BIIX-CI scale, which was developed to define a reasonable time for
      doing a surgical procedure and to define vital function stability. The 3 levels
      of clinical state are graded as compensated (range, 16-30 points), subcompensated
      (range, 31-40 points), and decompensated (> 40 points). The third concept is the
      reasonable succession in surgical procedures. It is advantageous to do similar
      operations simultaneously at compensated and subcompensated states. Dissimilar
      surgical interventions should be done in succession during the course of a single
      anesthesia or at different times according to the grading of emergency (urgent,
      postponed, and planned).

PMID- 7586823
TI  - Biomechanical effects of different surgical procedures on the extensor mechanism
      of the patellofemoral joint.
AB  - Loadbearing stresses in the patellofemoral joint were studied at different
      degrees of flexion before and after various surgical techniques recommended to
      treat knee disorders. Surgical procedures intended to reduce the intensity of
      stress were analyzed experimentally. The study was done using different
      experimental methods on whole knee specimens from fresh human cadavers that were
      not treated with formaldehyde. The results indicate that the most predictable
      procedure for increasing surface area and decreasing patellar stress is a
      combined procedure of anterior displacement of the anterior tibial tubercle by 1
      cm while displacing it 0.5 to 1 cm medially.

PMID- 7586824
TI  - The nerve endings of the acetabular labrum.
AB  - The nerve endings of the human acetabular labrum were investigated. Twenty-three
      acetabular labra were obtained from 24 fresh human cadavers, stained with
      Suzuki's silver impregnation and an immunohistochemical technique for neurogenic
      specific protein S-100, and examined by light and electron microscopy. Ramified
      free nerve endings were seen in all specimens by silver staining, and also were
      observed by the immunohistochemical technique for S-100 protein. Sensory nerve
      end organs, such as a Vater-Pacini corpuscle, Golgi-Mazzoni corpuscle, Ruffini
      corpuscle, and articular corpuscle (Krause corpuscle), were observed by silver
      staining. Collagen fibers were scattered sparsely in the superficial layer of the
      labrum, and nerve endings were observed mostly in this region. Collagen fibers
      were sparse, and nerve endings also were observed in some regions among the
      collagen fiber bundles in the inner layer. Innervation of the acetabular labrum
      was confirmed in this study, suggesting that nerve endings in the labrum may be
      involved in nociceptive and proprioceptive mechanisms.

PMID- 7586825
TI  - Tibiotalar contact area. Contribution of posterior malleolus and deltoid
      ligament.
AB  - Sixteen fresh ankle specimens were tested under physiologic loads to evaluate the
      effect on the tibiotalar contact area of increasing-size posterior malleolar
      fracture fragments and disruption of the deltoid ligament. The tibiotalar joint
      was maintained in a neutral position, and contact areas were recorded on pressure
      sensitive film. Posterior malleolar fracture fragments of 25%, 33%, and 50% as
      visualized on lateral radiographs were created. The deltoid ligament was
      sectioned after the final fracture fragment was made. There was a corresponding
      decrease of 4%, 13%, and 22% in tibiotalar contact area with the increasingly
      larger fracture fragments. The final disruption of the deltoid ligament did not
      alter the contact area. Statistical analyses using Student's t-test showed a
      statistically significant decrease in tibiotalar contact area in the samples with
      a fracture fragment of 33% and 50% involvement of the joint as compared with the
      control samples. Transection of the deltoid ligament produced no statistically
      significant further change in contact area. Displaced posterior malleolus
      fractures produce a significant decrease in contact area with 33% or greater
      involvement of the joint, which may predispose the tibiotalar joint to
      degenerative changes that should be lessened by anatomic reduction and internal
      fixation. Disruption of the deltoid ligament does not appear to alter contact
      area further, supporting the concept of repair as optional.

PMID- 7586826
TI  - The axes of rotation of the thumb interphalangeal and metacarpophalangeal joints.
AB  - The axes of rotation of the thumb interphalangeal and metacarpophalangeal joints
      were located using a mechanical method. The interphalangeal joint axis is
      parallel to the flexion crease of the joint and is not perpendicular to the
      phalanx. This offset of the axis with respect to the phalanx explains the ulnar
      deviation and pronation that occurs with flexion of the interphalangeal joint.
      The metacarpophalangeal joint has 2 fixed axes: a fixed flexion-extension axis
      just distal and volar to the epicondyles, and an abduction-adduction axis related
      to the proximal phalanx passing between the sesamoids. Neither axis is
      perpendicular to the phalanges. All physiologic motion for these joints occurs
      about the axes. These are the mechanical axes of the joints through which the
      muscles and external forces act. Knowledge of their location should help in
      constructing prosthetic joints and in planning reconstructive surgery such as
      tendon transfers.

PMID- 7586828
TI  - Work of flexion after flexor tendon repair according to the placement of sutures.
AB  - Tendon repairs comparing dorsal or volar placement of sutures were done on 36
      flexor profundus tendons from 9 canine cadaveric paws. Three suture techniques
      were used. Work of flexion as a measure of resistance to tendon gliding was
      measured in the following groups: Groups 1 and 2: 4-strand Savage technique with
      5-0 core suture, dorsal or volar placement; Groups 3 and 4: 4-strand Savage
      technique with 4-0 core suture, dorsal or volar placement; and Groups 5 and 6:
      tendon splint technique, dorsal or volar placement. The increase in work of
      flexion values were 11.3%, 14.1%, 12.2%, 37%, 20.5%, and 92.7% for Groups 1
      through 6, respectively. The increase in work of flexion value in Group 4 was
      significantly greater than that in Group 3, and the value in Group 6 was
      significantly greater than Group 5. These data suggest that the work of flexion
      after tendon repair was influenced by the location of the suture material; volar
      location of suture material significantly increased the work of flexion value.

PMID- 7586827
TI  - Vascularized allogeneic joint, muscle, and peripheral nerve transplantation.
AB  - Joint, muscle, and peripheral nerve allotransplantation was done with short-term
      cyclosporine immunosuppression. To investigate the effectiveness of this regimen,
      the allografts were examined after withdrawal of cyclosporine. Using inbred rats,
      vascularized orthotopic allotransplantation of the knee joint, rectus femoris
      muscle, and great saphenous nerve was done across a major histocompatibility
      complex barrier. Cyclosporine was administered for 4 to 6 weeks postoperatively,
      and the grafts were observed until Week 12. Long-term administration of
      cyclosporine and nonvascularized transplantation were used as controls. Although
      rejection of the allografts could be delayed for 2 to 3 weeks after the
      withdrawal of cyclosporine, all transplanted joints, muscles, and nerves
      eventually were rejected completely and immunotolerance could not be induced. The
      joint allografts at first achieved bony union, but eventually were destroyed
      because of pathologic fractures. In the group treated with long-term
      immunosuppression, the allografts showed no rejection and functional improvement
      was obtained. However, rats given a high dose (10 mg/kg per day) of cyclosporine
      died from adverse effects of the drug by Week 12. In the nonvascularized
      treatment group, the results were poor in every patient, and the need for graft
      vascularization for skeletal tissue allotransplantation was confirmed.

PMID- 7586829
TI  - Bone growth and modeling changes induced by periosteal stripping in the rat.
AB  - In this study, the changes in longitudinal bone growth and metaphyseal modeling
      induced by middiaphyseal periosteal stripping in the rat femur were analyzed by
      means of histomorphometrical techniques. One hundred forty-four male 30-day-old
      Sprague-Dawley albino rats distributed in 4 groups of 36 were studied: a control
      group, a sham group, a group with middiaphyseal right femoral periosteal
      stripping, and a group with a polyethylene ring wrapped around the stripped zone.
      The animals were euthanized at 1, 2, or 4 weeks from the start of the experiment,
      after double tetracycline labeling. A statistically significant, albeit small,
      longitudinal overgrowth of stripped femurs was observed after a latency period of
      2 to 4 weeks. The metaphyseal diameters were greater in stripped femurs than
      nonstripped femurs. This finding was associated with a lower osteoclastic index
      in the external metaphyseal surface and with a lower bone formation rate in the
      internal surface of the metaphyseal cortex. These latter findings have not been
      reported previously in the literature and may support the role of the periosteum
      in controlling metaphyseal modeling.

PMID- 7586830
TI  - Autoclaved autograft bone combined with vascularized bone and bone marrow.
AB  - In this study, the authors investigated enhancing the results of autoclaved
      autograft bone by combining it with a vascularized bone graft and supplementing
      it with autogenous bone marrow for replacement of a 2-cm tibial defect in the
      rabbit model. The study was divided into 4 groups. Group I consisted of
      autoclaved autograft bone only; Group II, autoclaved autograft bone and
      vascularized bone graft; Group III, autoclaved autograft bone and autogenous bone
      marrow; and Group IV, autoclaved bone and autogenous bone marrow and vascularized
      bone graft. The vascularized bone graft was provided by the ipsilateral fibula,
      pedicled on the peroneal vessels, and transposed to sit alongside the autoclaved
      bone. In Group I, all grafts had nonunion at 16 weeks. In Group II, new bone
      formation was seen at the proximal and distal site of the autoclaved bone, host
      bone, and vascularized fibular graft junction as early as 2 weeks, and bony union
      occurred at the 16th week. The autogenous bone marrow-supplemented groups (III
      and IV) had new bone formation along the entire length of the autoclaved bone.
      Bony union at the proximal and distal junction was seen as early as 4 weeks,
      extending to the entire autoclaved bone by the eight week (98% of the cases with
      1 case of infection). Histologic examination showed revascularization and
      capillary ingrowth into the autoclaved bone at 16 weeks, with a significantly
      improved torsional stiffness when compared with the groups without autogenous
      bone marrow supplementation. The addition of vascularized bone graft resulted in
      an improved union rate as compared with the autoclaved bone alone. Autogenous
      bone marrow supplementation, in addition to the vascularized bone graft, resulted
      in rapid new bone formation all around the autoclaved bone, early
      revascularization and incorporation of the autoclaved bone, and a significantly
      improved torsional stiffness of the reconstruction.

PMID- 7586833
TI  - Treatment of neglected complicated multiple musculoskeletal injuries.
AB  - Two hundred eighty-nine patients with multiple bone fractures who had combined
      impairment of bones and soft tissues were treated from 1960 to 1993 in the
      authors' institution. All patients were transferred from local hospitals of the
      Moscow district between several months and 3 years after trauma, and had
      neglected fractures complicated by dislocations, false joints, and imperfectly
      united bone fractures. The authors prefer an individual approach to patient
      treatment and used simultaneous surgical intervention on several bone segments
      using stable osteosynthesis with AO-POLDI plates and the Ilizarov apparatus. Two
      stage operations were done in cases of > or = 3 injured segments. Positive
      results with restoration of the extremity and its supporting motor systems were
      obtained in 96% of patients.

PMID- 7586832
TI  - Unwashed wound drainage blood. What are we giving our patients?
AB  - Wound drainage blood was collected after total joint arthroplasty was completed
      in 13 consecutive patients. Peripheral blood samples were collected in the
      recovery room and at 6 hours postoperatively for all 13 patients. A standard
      enzyme-linked immunosorbency assay was done to quantify tumor necrosis factor
      alpha, interleukin-1 alpha, interleukin-6, and interleukin-8 levels in the
      samples. At 6 hours postoperatively, the levels of cytokines were elevated
      significantly in the peripheral and drainage blood serum. In particular, the
      drainage blood serum had the most dramatic increase for all cytokines, which was
      significant. Reinfusion of unwashed filtered postoperative wound drainage blood
      has been shown not to be entirely benign; pyrogenic transfusion reaction is the
      most commonly reported adverse effect, but hemodynamic instability with
      hypotension and even myocardial infarction have been reported. The cause of these
      adverse events has not been defined clearly, but may be secondary to the infusion
      of cytokines. The present study showed the presence and significant elevation of
      the cytokine levels in the wound drainage blood. A comprehensive review of the
      literature revealed that unwashed drainage blood is a relatively dilute blood
      product lacking normal clotting factors and having numerous other undesirable
      components that may mitigate against its routine use in lieu of predeposited
      autologous or homologous blood. This is of interest because there is evidence
      indicating that wound drainage blood reinfusion may be unnecessary in total joint
      arthroplasty when autologous blood is available. Use of drains in this surgery
      also may be unnecessary and has been shown to increase the amount of blood loss
      and the need for transfusion.

PMID- 7586834
TI  - Tutorial. Molecular biology for the clinician. Part II. Tools of molecular
      biology.
AB  - This is the second of a series of tutorials on molecular biology for the
      clinician. Part I introduced general principles of nucleic acid and gene
      structure. This tutorial will build on those general principles and describe some
      of the commonly used techniques employed in research and diagnosis to examine
      genes and gene function. The tools of molecular biology include recombinant DNA
      techniques that have revolutionized the study of DNA and genetic information.
      Recombinant DNA technology allows the isolation of specific regions of
      chromosomal DNA and the recovery of unlimited quantities of that DNA for
      analyses, including determination of the nucleotide sequence of genes,
      examination of the mechanisms of gene regulation, and the identification of gene
      products (RNA and protein).

PMID- 7586831
TI  - Bilateral simultaneous rupture of the Achilles tendon. A rare traumatic injury.
AB  - Two case reports describe simultaneous bilateral Achilles tendon rupture in
      healthy athletes. This injury has not been previously reported as an acute injury
      in healthy patients. Isolated bilateral ruptures have occurred in patients
      receiving long-term corticosteroid therapy. Achilles tendons that have been
      exposed to chronic wear from repeated stress generated through physical activity
      show evidence of degeneration in their microstructure and are more prone to
      rupture than are healthy tendons. Specific bilateral forces generated through the
      Achilles tendons of experienced older gymnasts predispose these persons not only
      to chronic bilateral tendon wear but also to acute bilateral simultaneous
      ruptures during specific maneuvers.

PMID- 7586835
TI  - Paraparesis in an 83-year-old woman.

PMID- 7586836
TI  - Pelvic polyfractures in children. Radiographic diagnosis and treatment.
AB  - Results of clinical and radiographic examinations of 43 patients, 4 to 15 years
      old, with pelvic polyfractures during acute- and long-term periods of trauma, and
      postmortem and experimental data were presented. A high rate of diagnostic
      mistakes and treatment failures in patients with pelvic polyfractures are
      defined. Depending on the location and pattern of pelvis injuries, the main
      reasons for complications are determined. A technique of external fixation with
      the application of a pivot device for managing pelvic polyfractures in children
      is described. The efficacy of the proposed curative tactics is shown by treatment
      results of 12 patients with pelvic polyfractures.

PMID- 7586837
TI  - Introduction of general military surgery. General rigidity of the whole body or
      traumatic torpor (stupor). How long should one wait before surgery at general
      rigidity? Effect of the rigidity upon the surgical outcome. 1865.

PMID- 7586838
TI  - Organ-sparing treatment for closed spleen injuries in children.
AB  - The results of organ-saving treatment for 84 children with closed transcapsular
      spleen rupture were studied. Criteria for the stipulation of differential
      curative tactics were present. Twenty-five children were treated conservatively.
      In 57 patients, different endosurgical manipulations were done. Laparotomy was
      done in 5 patients, including 3 patients who primarily had endosurgical
      treatment. Long-term results were studied for 29 children. The followup period
      was from 3 months to 4 years. Investigators showed that recommended tactics
      helped save organs in > 90% of children with transcapular splenic injuries. The
      possibility of restoring splenic structure and functional activity and preventing
      hyposplenism was proven by orthotopic saving of injured spleens.

PMID- 7586839
TI  - New concepts of the pathogenesis in the healing process of gunshot wounds.
AB  - By applying cytogenetic methods to the study of gunshot injuries, the authors
      showed that disturbances of the chromosomic apparatus integrity occurred. These
      disturbances are present for a long period and aggravate the severity of the
      wound-healing process.

PMID- 7586840
TI  - Mortality caused by polytrauma.
AB  - A study of the injury fatality rate in an adult population was done in the Moscow
      region. Investigators determined that side by side with the severity of injury,
      the direct causes of death were erroneous diagnosis, ungrounded delay of surgical
      interventions, and lack of and insufficient use of necessary medical care. They
      also showed that the attention of administrative and public health agencies to
      the material/technical equipment of prehospital and hospital medical service, and
      to the training of medical personnel, was insufficient and that activity on
      accident prevention was inadequate. Determination of causes will help to create
      concrete measures to decrease injury fatality.

PMID- 7586841
TI  - Postoperative shoulder rotators strength in stages II and III impingement
      syndrome.
AB  - In healthy subjects, the shoulder internal rotator muscle strength overrides the
      external rotators. This has been confirmed in different isokinetic studies
      showing the ratio of the relative strengths of the internal to external rotators
      to range from 1.3 to 1.5 points, depending on the study. The authors previously
      reported a decrease in the relative strength ratio of the internal to external
      rotators to close to 1 in patients suffering from Neer's impingement syndrome.
      The aim of the present study was to assess, long after surgery (mean, 44.5
      months), the isokinetic strength performance of shoulder rotator muscles in 72
      patients who had had operative treatment for chronic subacromial impingement
      using anterior acromioplasty, sometimes combined with cuff repair surgery. Tests
      were conducted with a Biodex Multi-Joint System in the plane of the scapula and
      in 45 degrees abduction at 60 degrees and 180 degrees per second. Peak torque and
      average power were calculated. The mean ratios of relative strengths of the
      internal to external rotators ranged from 1.3 to 1.6 points depending on the
      parameter studied and the test speed. These results indicate that surgery
      restores normal muscular balance between shoulder rotator muscles affected by the
      impingement syndrome.

PMID- 7586846
TI  - Femoral artery thrombus complicating open reduction of congenital hip
      dislocation.
AB  - There are no reports in the literature of femoral artery thrombi occurring as a
      complication of open reduction of congenital hip displacement. In an 11-month-old
      female infant, a femoral artery thrombus most likely formed as a result of
      compression of the femoral artery with a muscle retractor hook used in performing
      Ludloff's procedure. Femoral artery thrombi should be considered as a possible
      complication of reduction of congenital hip dislocation with Ludloff's procedure.

PMID- 7586843
TI  - The role and significance of research in a specialized trauma center.
AB  - Compared with nonspecialized hospitals, specialized trauma centers on university
      or research institute campuses are distinguished by lower mortality, morbidity,
      and mean hospital stay because of the permanent influence research has on the
      results of clinical practice. Close collaboration between researchers and
      clinicians in St Petersburgh Trauma Shock Center helped to develop medical
      knowledge and technology in the initial prognostic evaluation of the injured
      patient in shock, to improve surgical protocols in relation to prognosis, and to
      develop treatment for endotoxemia and sepsis.

PMID- 7586844
TI  - Pain and pathology in lumbar disc hernia.
AB  - The authors analyzed pain drawings of patients having lumbar disc surgery and
      tried to correlate pain pattern to disc pathology and level. Preoperatively,
      patients having spinal surgery were asked to draw on a standardized form the
      localization, postural variation, and modality of their pain. In this study, 185
      consecutive patients with unilateral and unisegmental L4-L5 and L5-S1 hernias
      were analyzed. The pain drawings were coded and read blindly; each drawing was
      divided operationally into anatomic areas, and the type of pain symbol in each
      pixel was recorded, digitized, and analyzed by stepwise discriminant analysis.
      For predicting the level of the lesion, the most important variables were pain on
      the anterolateral aspect of the leg (L4-L5) and pain radiating to the posterior
      aspect of the foot (L5-S1). For predicting the grade of herniation, the most
      discriminative factors were pain radiating to the foot (sequestrated hernia) and
      bilateral back pain (protruded hernia). Pain drawing facilities communication and
      documentation. In addition, it is an aid to diagnose the level and degree of the
      hernia, and therefore is useful for selecting patients who might benefit from
      disc surgery. For scientific purposes, data are digitized easily, allowing
      analyses of large populations.

PMID- 7586845
TI  - Cementless total hip arthroplasty in patients with osteonecrosis of the femoral
      head.
AB  - The authors studied 61 patients (78 hips) who had avascular necrosis of the
      femoral head, seen in followup for an average of 7.2 years (range, 6-9 years)
      after they had primary cementless porous-coated total hip arthroplasty. This
      study was undertaken to determine whether cementless porous-coated prostheses
      have any merit over reported cemented total hip arthroplasty using contemporary
      techniques. The average age of the patients at the time of surgery was 48 years
      old (range, 20-73 years). The average preoperative hip score was 45.6 points
      (range, 28-75 points), which improved to 90.3 points (range, 34-100 points) at
      the 7.2-year followup examination. Sixteen of 78 arthroplasties failed in the
      period of followup, for an overall failure rate of 20.5%. Of the failed hips, 11
      had femoral component loosening, 4 had femoral and acetabular component
      loosening, and 1 had excessive wear in the polyethylene liner. Four femoral
      components and 5 acetabular components were revised. Twenty-one of the 78 hips
      (27%) had an average of 5.6 mm (range, 3-9 mm) of wear in the polyethylene liner.
      Sixteen (20.5%) of 78 hips had acetabular and femoral periprosthetic osteolysis,
      and 22 (28.2%) hips had femoral periprosthetic osteolysis only. The cementless
      total hip arthroplasty in this series had a higher incidence of aseptic loosening
      of the femoral component, polyethylene liner wear, and periprosthetic osteolysis
      than that reported for cemented total hip arthroplasty using contemporary
      techniques.

PMID- 7586842
TI  - Myxoid and globular degeneration of nerves in the shoulder joint.
AB  - Characteristic degeneration of the nerves in shoulder joints was recognized in 26
      of 35 capsules (74.3%) from 20 cadavers. No left or right or gender differences
      were found. Histologic features of the nerves were (1) thickening of the
      perineurium, (2) myxoid degeneration in the endoneurium, and (3) hyaline globular
      structures with a whorled, oligocellular appearance regarded as Renaut bodies.
      The results of histochemical and electron microscopic studies showed prominent
      degenerated collagen fibers in the globular areas. These features resembled those
      found in the fusiform swelling in the axillary nerve branch to the teres minor
      muscle, believed to be caused by chronic nerve compression. Sixty percent of the
      degenerated nerves occurred in the anteroinferior and posteroinferior portions of
      the capsule, an area that is considered to be innervated by the axillary nerve.
      No correlation between age and severity of these degenerative nerve changes was
      noted. Compression of the axillary nerve and inferior joint capsule caused by
      repetitive shoulder movement such as forward flexion, abduction, and external
      rotation of the humerus might result in this form of nerve degeneration found
      histologically over a lifetime without necessarily causing clinical symptoms.

PMID- 7586847
TI  - Injury to infrapatellar branch of saphenous nerve in arthroscopic knee surgery.
AB  - Injury to the infrapatellar branch of the saphenous nerve has been reported as a
      complication of arthroscopic examination and surgery of the knee. The authors
      studied the anatomic distribution of this branch in cadavers, and investigated
      the incidence of this complication in 68 patients. The results of anatomic study
      showed that blind puncture is safe within an approximate 30-mm area from the
      medial margin of the patella at the level of midpatella, and within an
      approximate 10-mm area from the medial margin of the patellar ligament at the
      level of the distal pole of the patella. In 30% of examined cadavers, the
      infrapatellar branch of the saphenous nerve transverses and runs laterally before
      it crosses the proximal edge of the tibia. Anatomic findings indicated that blind
      puncture to the knee in a 90 degrees flexion position should be done horizontally
      and parallel to the articular surface to reduce the incidence of nerve injury.
      The results of this study of patients who had arthroscopy from 1990 to 1991
      revealed a 22.2% incidence rate of sensory disturbances in the area where the
      infrapatellar branch is distributed. The incidence can be minimized by clarifying
      the distribution of the infrapatellar nerve branch in relation to palpable
      landmarks.

PMID- 7586848
TI  - Vascular assessment in the neuropathic diabetic foot.
AB  - Diabetic foot infections, a common source of morbidity and mortality, often have
      been related to vasculopathy and neuropathy in its etiopathogenesis, especially
      in the elderly person with diabetes. However, blood flow in the neuropathic
      diabetic foot has not been evaluated extensively, and there is evidence of
      abnormal blood flow patterns in the neuropathic diabetic foot unrelated to
      ischemia. The authors studied young persons with diabetes, with varying degrees
      of neuropathy, to assess the extent of vasculopathy in their lower limbs. Twelve
      young persons with insulin-dependent (Type I) diabetes (mean age, 36.1 +/- 1.975
      years) and peripheral neuropathy, all of whom had previous surgery for diabetic
      foot infections, were identified. Confirmatory evidence of neuropathy was made
      using electromyographic studies and clinical tests that showed severe peripheral
      neuropathy. The results of vascular assessment of both lower limbs did not reveal
      any change in the pulse wave velocities from the popliteal to the digital vessels
      of the big toe as compared with correspondingly matched controls. There also was
      no significant stenosis in any of the vessels studied as far as the level of the
      dorsalis pedis and posterior tibial vessels. The normal triphasic pattern of
      arterial blood flow was lost. A monophasic pattern was present in all patients
      with prolonged diastolic flow at the level of the dorsalis pedis and posterior
      tibial arteries and distally. The pulsatility index was 3.14 +/- 0.81 as compared
      with 9.85 +/- 4.2. Mean toe pressures in the patient with diabetes was 64.17 +/-
      20.87 mm Hg as compared with 98.23 +/- 10.12 mm Hg in controls. A linear
      correlation of decreasing toe pressures with increasing severity of neuropathy
      was seen (R = 0.7). The data suggest that changes exist in the blood flow
      patterns in young patients with diabetes and neuropathy, even in the absence of
      lower limb ischemia.

PMID- 7586849
TI  - Strokes mimicking peripheral nerve lesions.
AB  - Sensory-motor deficit in a peripheral nerve pattern due to brain lesion is rarely
      documented. We report on seven patients with a clinical manifestation of sensory
      motor deficit, imitating peripheral nerve involvement, due to lacunar brain
      infarcts verified by brain computed tomography scan. Five of the patients had an
      ulnar nerve-like deficit and two median nerve-like deficits. The infarcts were
      located in the thalamus and the corona radiata. No clinical or
      electrophysiological evidence for peripheral nerve involvement was found. The
      unusual peripheral nerve pattern of lesions caused by lacunar brain infarcts can
      be defined as an additional lacunar syndrome and must be taken into consideration
      in the clinical evaluation of peripheral nerve deficits with normal nerve
      conduction velocity.

PMID- 7586850
TI  - Positron emission tomographic study of late-onset cryptogenic symptomatic
      seizures.
AB  - Ten patients with epilepsy of unknown origin, starting after the age of 50 years,
      and without clear evidence of cognitive decline were studied with positron
      emission tomography, using the steady state technique with 15O. Cerebral blood
      flow and oxygen metabolism were significantly decreased in all cortical areas. No
      focal areas of hypometabolism were detected. Treatment with phenytoin did not
      influence the results. It is suggested that late-onset seizures could be the
      premonitory signs of a progressive encephalopathy of unknown origin.

PMID- 7586851
TI  - Delayed onset generalised dystonia after cyanide poisoning.
AB  - A 27 year old female developed delayed onset of persistent generalized dystonia
      following a suicidal attempt with potassium cyanide. Cranial CT scan showed
      bilateral putaminal hypodensities which were also seen on MRI scans to be
      hypointense on T1 and hyperintense on T2 weighted images. Multimodality evoked
      potentials were normal. An improvement was noted with levodopa.

PMID- 7586852
TI  - High thoracic neurinoma mimicking femoral neuralgia.
AB  - We report a case of spinal neurinoma at a high thoracic level, whose main
      presentation was intractable pain in a body part innervated by the right femoral
      nerve. Sensations of pain and temperature were impaired in the right thigh, but
      usual symptoms of myelopathy were undetectable. In conjunction with the other
      reports, this case suggests that spinal tumors at high thoracic levels can
      produce remote symptoms mimicking peripheral neuropathy such as femoral or
      sciatic neuralgia.

PMID- 7586854
TI  - Congenital pelvic arteriovenous malformation: a rare cause of sciatica.
AB  - A patient with a large congenital pelvic arteriovenous malformation presenting
      with irradiating pain to the leg, most likely due to sciatic nerve compression,
      is described. Congenital pelvic arteriovenous malformation are rare lesions,
      especially in males. Diagnosis was established by arteriography and contrast
      enhanced computed tomography scan. Surgical resection of the AVM relieved our
      patient of all symptoms. However, endovascular therapy, either as primary
      treatment or followed by conventional surgery is the treatment of choice. Pelvic
      arteriovenous malformations should be considered in the differential diagnosis of
      unexplained sciatica.

PMID- 7586853
TI  - Central neurocytoma: clinico-pathological study of 5 cases and review of the
      literature.
AB  - Five cases of central neurocytoma, confirmed by immunohistochemical and electron
      microscopy studies, are reported and 127 cases from the literature are reviewed.
      Central neurocytomas are more frequent than previously thought, and will be
      diagnosed with increasing frequency in the future, if intraventricular tumors
      with histological aspect of oligodendroglioma or ependymoma will be routinely
      studied by immunohistochemistry and electron microscopy. The occurrence of an
      intraventricular tumor with a typical MR aspect in a young patient should suggest
      preoperatively the diagnosis of neurocytoma. The positivity for synaptophysin and
      neuron specific enolase, the negativity for neurofilament protein and glial
      fibrillary acid protein, and the finding of elements of neuronal differentiation
      on electron microscopy, are the main pathological features of these tumors.
      Complete removal of the tumor mass without radiotherapy is the treatment of
      choice. The prognosis is usually favorable without recurrence.

PMID- 7586855
TI  - 'De novo' aneurysm formation: report of two cases.
AB  - We report 2 cases of 'de novo' aneurysm formation in a vessel which appeared to
      be normal at a previous angiography. The first patient developed an anterior
      communicating artery aneurysm nine years after occlusion of the right internal
      carotid artery by Gianturco coils for the treatment of a giant intracavernous
      carotid aneurysm. In the second case a 'de novo' aneurysm of the internal angle
      A1-A2 segment of the left anterior cerebral artery developed 6 years after
      successful clipping of another aneurysm of the same location. De novo formation
      of an aneurysm in a vessel which was found to be normal in a previous
      angiographic study, may occur as result of hemodynamic changes, such as after
      internal carotid occlusion or in presence of an arteriovenous malformation or
      variations of the circle of Willis. However, definite hemodynamic changes may
      also be absent. We conclude that patients operated on for aneurysm clipping must
      be periodically explored by magnetic resonance angiography to evaluate the
      possibility of de novo appearance of another aneurysm.

PMID- 7586856
TI  - Clivus and cervical spinal osteomyelitis with epidural abscess presenting with
      multiple cranial neuropathies.
AB  - A 65-year-old diabetic man with a history of otitis was admitted with headache,
      neck and shoulder pain and cranial nerve abnormalities including sixth, seventh
      and twelfth nerve palsies, hearing loss and ptosis. Lumbar puncture revealed an
      elevated CSF protein and pleocytosis. Imaging procedures demonstrated
      osteomyelitis of the clivus that involved the epidural space and extended within
      the prevertebral space to the cervical spine. The patient improved after
      treatment with antibiotics and immobilization of the neck. This case illustrates
      the importance of recognizing infections of the clivus in patients with cranial
      nerve abnormalities.

PMID- 7586858
TI  - Localization in impaired spatial vision.
AB  - The present study provides clear clinico-anatomical evidence for localization of
      the spatial vision pathway. We report the case of a 29-year-old woman with severe
      spatial vision impairment. Magnetic resonance imaging revealed distinct bilateral
      and symmetrical occipito-parietal damage. The right lesion affected the superior
      parietal lobule, the dorsolateral portion of the occipital lobe, the precuneus,
      and the cuneus. The left lesion affected the superior parietal lobule, the
      dorsolateral portion of the occipital lobe, the precuneus, an upper part of the
      cuneus, and the posterior portion of the middle and inferior temporal gyri.

PMID- 7586857
TI  - Chordoma of the lower cervical spine.
AB  - Vertebral chordomas are rather rare tumours, especially in the lower cervical
      region. We present a patient with a C7 vertebral body chordoma and a discussion
      of pertinent literature is given. Only three C7 chordomas have been reported
      previously. Diagnosis is sometimes difficult to establish and is based on
      radiological examinations. Once the histological diagnosis is available, one
      should aim at a total resection. If this is not possible, adjuvant radiotherapy
      should be given. For limited cervical lesions, we advise a corporectomy with
      fusion by an iliac crest graft and osteosynthetic plate stabilisation.

PMID- 7586860
TI  - Cysticercosis mimicking brain tumor: the role of albendazole as a diagnostic
      tool.
AB  - We report a patient with seizures and a single ringlike enhancing lesion on MRI
      that resembled a low-grade glioma. The patient received a diagnostic trial with
      albendazole on the assumption that this lesion could be a cysticercus. Follow-up
      showed resolution of the brain lesion in 4 weeks. Albendazole administration to
      patients with single ringlike enhancing lesions may obviate unnecessary surgical
      procedures in selected cases.

PMID- 7586859
TI  - Hydrocephalus in Guillain-Barre syndrome.
AB  - Hydrocephalus and pseudotumour cerebri are a rare complication of Guillain-Barre
      syndrome (GBS), occurring in about 4% of the cases. The high concentration of
      cerebrospinal fluid (CSF) protein may lead to a decreased CSF absorption in
      arachnoid villi. A 10-year-old boy with GBS and hydrocephalus is presented. A
      mechanical ventilation was required 7 days after admission and he had been on the
      mechanical ventilation for 6 weeks. Lumbar puncture performed on admission
      revealed clear CSF with an opening pressure of 15 cm H2O and no cells, a normal
      glucose level and a protein of 240 mg/dl. He complained of headache and diplopia
      11 weeks after admission. Fundoscopy revealed papilloedema, and bilateral mild
      abducens pareses were also detected. Magnetic resonance imaging displayed a
      communicating hydrocephalus and interstitial oedema. A ventriculo-peritoneal
      shunt relieved the symptoms of intracranial hypertension. In GBS, serial computed
      tomographic scans should be performed in patients with headache and papilloedema.
      Hydrocephalus may develop in GBS.

PMID- 7586861
TI  - Transverse myelopathy complicating mixed connective tissue disease.
AB  - We report the case of a 46-year-old female patient with transverse myelitis
      complicating mixed connective tissue disease (MCTD). She responded well to
      steroid and immunosuppressive therapy. Unlike in systemic lupus erythematosus
      (SLE), transverse myelopathy in association with MCTD is very rarely described.
      The mechanisms, diagnosis and treatment of transverse myelitis in MCTD are
      briefly discussed.

PMID- 7586862
TI  - Treatment of complex partial status epilepticus unmasking acute intermittent
      porphyria in a patient with resected anaplastic glioma.
AB  - We report a 42-year-old woman with an established complex partial seizure
      disorder, who presented in refractory complex partial status epilepticus, the
      treatment of which with lorazepam, phenytoin, carbamazepine, and pentobarbital
      precipitated an attack of acute intermittent porphyria (AIP). The subsequent
      clinical course and management with gabapentin is discussed.

PMID- 7586863
TI  - Progressive late delayed postirradiation encephalopathy with Kluver-Bucy
      syndrome. Serial MRI and clinico-pathological studies.
AB  - The first pathologically documented case of progressive late delayed
      postirradiation encephalopathy in a 37-year-old man with Kluver-Bucy syndrome
      (KBS) is reported here. The pathological findings and clinical course of KBS with
      recurrent stroke-like episodes and partial epilepsy within a 7-year period
      following a 'safe dose' radiation therapy for pituitary tumor are presented.
      Serial magnetic resonance imaging shows, at different stages of the disease, a
      pontine infarct, enlarged temporal lobes with serpentine hyperintense signal at
      cortical gyri on T2-weighted and proton density MRI, and progressive brain
      calcification which appears hyperintense on T1-weighted images and hypointense on
      T2-weighted images.

PMID- 7586864
TI  - The black hole in Charley Toorop's "The three generations": a neuro-iconographic
      analysis and reconstruction.
AB  - The painting "The Three Generations" is considered one of the highlights in
      Charley Toorop's works. It essentially represents a self portrait of the artist
      herself, with John Radeker's sculpture of her father Jan Toorop, and her son
      Edgar Fernhout. The completion of this painting took 9 years (1941-1950).
      However, the left lower corner of the canvas, sometimes referred to as "the black
      hole", Charley's left thumb with the palette and the conspicuously raised right
      arm with the brush can be considered structural imperfections. During the last 5
      years of her life Charley Toorop suffered at least three cerebrovascular
      accidents, which raises the question whether the described pictorial inadequacies
      were of a neuropathological origin. Closer examination of the "black hole" area
      on the canvas disclosed a subtle ridge, as predicted and reconstructed by
      computer image manipulation. It is argued that Charley Toorop suffered multiple
      brain infarctions with subsequent partial visuo-spatial agnosia which prevented
      her from either recognizing and/or restoring the alleged imperfections in the
      painting "The Three Generations".

PMID- 7586865
TI  - SPECT of the cervical spine in the evaluation of neck pain after trauma.
AB  - In a retrospective study, the authors reviewed the use of SPECT in the evaluation
      of cervical spine abnormalities in 35 patients with persistent neck pain after
      trauma. Nineteen patients had normal bone SPECT studies, which, in addition to
      several volunteers, were used to identify tomographic landmarks and determine
      resolution of individual vertebrae. Sixteen patients had abnormal SPECT results.
      When compared to final diagnosis, this group included seven (44%) patients with
      recent fractures, five (31%) patients with traumatic periostitis (periosteal
      injury resulting from severe strain), and four patients (25%) with mild cervical
      strain superimposed on degenerative changes. SPECT sensitivity in the detection
      of recent fractures was 100% with a specificity of 78%. SPECT detected occult
      fractures in 7 of 35 patients (27%), including 3 patients with normal radiographs
      and 4 patients with equivocal radiographs. Recent fractures were excluded in six
      of nine patients (67%) with known fracture identified on cervical spine
      radiographs and none of the patients with normal SPECTs had CT or MRI evidence of
      recent fractures. SPECT was useful in 1) the diagnosis of occult fractures or
      periostitis (periosteal injury) in patients with normal radiographs, 2)
      characterization of radiographic abnormalities (recent versus healed fractures),
      3) identification of active, possible post-traumatic osteoarthritis superimposed
      on chronic degenerative disease, and 4) eliminating or targeting subsequent
      imaging modalities, when appropriate. The authors conclude that bone SPECT has a
      valuable place in the diagnostic evaluation of patients with persistent neck pain
      after trauma.

PMID- 7586867
TI  - Quantitative comparison of prone and supine myocardial SPECT MIBI images.
AB  - The myocardial count distribution and the stress/rest ratio distribution were
      compared between prone and supine Tc-99m MIBI myocardial SPECT acquisitions.
      Ninety-nine male patients with a low stress supine inferior wall count underwent
      stress and rest acquisitions in the supine and prone positions successively. For
      each study, values depicting the inferior, anterior, septal, and lateral wall
      counts were extracted from a medioventricular normalized circumferential profile
      and underwent a statistical analysis (Student's paired t-test). On prone imaging,
      when compared to supine imaging, counts showed a highly significant mean relative
      increase of 11% +/- 1% in the inferior wall and of 7% +/- 1% in the septum.
      Conversely, these counts showed a significant mean relative decrease of 4% +/- 1%
      in the anterior wall and of 3% +/- 1% in the lateral wall. Moreover, the inferior
      wall stress/rest ratio showed a highly significant mean relative increase (6% +/-
      2%). The prone position is probably preferable for interpreting the inferior wall
      and septum, where relative counts are enhanced, as with TI-201, and because the
      inferior stress-rest discrepancies are reduced in that position. But the anterior
      and lateral wall information is impaired in the prone position. The authors
      suggest, in case of a low stress supine inferior count, the combination of both
      positions, which is feasible with Tc-99m MIBI, in order to prevent a misleading
      interpretation.

PMID- 7586869
TI  - Incorporation of right ventricular counts as a bullseye artifact.
AB  - Although extensive information regarding right ventricular uptake of thallium and
      a variety of bullseye artifacts exist, previous reports have not recognized a
      bullseye artifact due to right ventricular uptake of thallium. This case report
      again emphasizes the need for careful inspection of tomographic images while
      interpreting the bullseye. It is the first reported case of a bullseye artifact
      due to incorporation of right ventricular counts into the bullseye representation
      of left ventricular septal wall counts.

PMID- 7586866
TI  - Supine and prone SPECT Tc-99m MIBI myocardial perfusion imaging for dipyridamole
      studies.
AB  - Aartifactual inferior wall defects of perfusion are a source of frequent concern
      during TI-201 exercise stress redistribution SPECT imaging in the supine
      position. These artifactual changes also affect Tc-99m sestamibi dipyridamole
      myocardial perfusion studies with supine SPECT yielding a specificity of only 58%
      for right coronary artery (RCA) disease. Complementary SPECT prone imaging will
      enhance this specificity for inferior wall abnormalities to 79% (P < 0.05) and is
      recommended for more accurate assessment of RCA stenosis, whether the patient
      challenge is pharmacological or by exercise.

PMID- 7586868
TI  - Avoidance of upward creep artifact during TI-201 myocardial perfusion tomography
      using adenosine infusion. A case report.
AB  - Upward motion of the heart during tomographic data acquisition of stress TI-201
      myocardial perfusion images may lead to artifacts in the reconstructed tomograms.
      The authors report a patient in whom this occurred, giving the impression of
      reversible perfusion defects. Although correction of the raw data abolished the
      artifact, a separate study using adenosine vasodilation produced normal images.
      The authors conclude that adenosine vasodilation should be considered in
      preference to dynamic exercise in patients at risk of this artifact, such as
      those with a high exercise tolerance.

PMID- 7586870
TI  - Premature extravasation. A bleeding site identified during the dynamic phase of
      Tc-99m red blood cell bleeding scintigraphy.
AB  - Tc-99m RBC scintigraphy is favored by many investigators because it provides the
      ability to image the abdomen over a prolonged period of time, thereby allowing
      identification of delayed bleeding sites that are frequently encountered due to
      the intermittent nature of gastrointestinal bleeding. The authors describe a case
      of bleeding scintigraphy with labeled red blood cells in which the bleeding site
      was identifiable only on the dynamic blood-flow and first static images. On later
      images, the labeled blood cells had spread throughout the colon, rendering
      localization of the actual bleeding site impossible. Two previous red blood cell
      scintigraphies and a subsequent contrast angiogram did not reveal sites of active
      bleeding. As illustrated by this unusual case, factors governing timing and
      visualization of abnormal bleeding sites are discussed, as is a differential
      diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding
      scintigraphy.

PMID- 7586871
TI  - Three-phase abdominal scintigraphy in lupus vasculitis of the gastrointestinal
      tract.
AB  - Gastrointestinal vasculitis is a recognized but frequently misdiagnosed
      complication of systemic lupus erythematosus. The authors investigated the
      usefulness of three-phase Tc-99m pyrophosphate abdominal scintigraphy for
      identifying areas of vasculitis in patients with systemic lupus erythematosus who
      have gastrointestinal symptoms (diarrhea or abdominal pain). Among patients with
      gastrointestinal symptoms, 62 of 82 (75%) patients showed positive scan results,
      suggesting gastrointestinal vasculitis. Among patients without gastrointestinal
      symptoms, 6 of 43 (13%) patients showed positive scan results. Although three
      phase Tc-99m pyrophosphate abdominal scintigraphy cannot provide a definite
      diagnosis of vasculitis of the gastrointestinal tract, it is a noninvasive and
      convenient method for suggesting and monitoring gastrointestinal vasculitis.

PMID- 7586872
TI  - Parathyroid adenomas without sestamibi retention.
AB  - The authors describe two patients in whom parathyroid adenomas were successfully
      localized with a Tc-99m sestamibi/pertechnetate subtraction technique, but who
      did not exhibit differential sestamibi retention on delayed imaging. Although the
      frequency of this occurrence is unclear, it suggests that some parathyroid
      adenomas will be missed if reliance is placed on sestamibi retention alone
      without simultaneous thyroid imaging.

PMID- 7586875
TI  - The diagnosis of anastomotic leak after gastroesophagostomy with biliary
      scintigraphy.
AB  - Tc-99m HIDA scintigraphy in a patient with septic complications after partial
      resection of the esophagus and gastroesophagostomy demonstrated a free bile leak
      through the anastomosis to the thoracic drains. Concomitant attempts to verify
      this with dye ingestion (methylene blue) and x-ray examinations were negative.

PMID- 7586874
TI  - Tc-99m antimony sulfate lymphoscintigraphy to demonstrate lymphatic communication
      between the peritoneal cavity and the scrotum.
AB  - Lymphatic complications in the groin from inguinal artery surgery include
      lymphoceles and lymphocutaneous fistulae. Lymphatic fistula between the
      peritoneal cavity and the scrotum developed in a patient after excision of a
      cavernous lymphangioma in the inguinal region. The communication was demonstrated
      by Tc-99m antimony sulfate lymphoscintigraphy.

PMID- 7586873
TI  - Breast cancer detection with Tc-99m tetrofosmin.
AB  - Myocardial SPECT imaging was performed with Tc-99m tetrofosmin. Intense focal
      uptake at the level of the left breast was observed. At mammography a breast
      carcinoma was suspected, which was confirmed after surgery. This may be the first
      report of neoplastic mammary uptake of Tc-99m tetrofosmin.

PMID- 7586876
TI  - The value of Tc-99m citrate scintigraphy in chronic osteomyelitis. An indicator
      of the involved bone.
AB  - The authors present a prospective analysis of Tc-99m MDP and Tc-99m citrate
      scintigraphy in 29 patients who were clinically suspected of having chronic
      osteomyelitis. All of the patients showed increased Tc-99m MDP uptake on bone
      scintigraphy involving the area of concern. However, Tc-99m citrate scintigraphy
      clearly identified the patients with osteomyelitis (N = 18) confirmed either by
      biopsy or clinical follow-up. Eleven patients who were free of osteomyelitis
      showed only minimal radiotracer uptake on Tc-99m citrate scintigraphy. These
      patients had other benign musculoskeletal diseases that were diagnosed by other
      imaging modalities. In addition to visually interpreting the scintigraphic
      images, a semi-quantitative analysis was performed by drawing regions of interest
      over the areas involved and the normal contralateral side, and patients with
      osteomyelitis were found to have lesion to nonlesion ratios of greater than 1.70.
      Because Tc-99m MDP is a nonspecific radiopharmaceutical for the evaluation of
      bone infection, other imaging agents have been investigated. Tc-99m citrate is a
      small molecule that makes it suitable to penetrate injured capillaries to the
      edema fluid known to be present in areas of infection. The authors conclude that
      Tc-99m citrate is a promising agent for localizing and showing the extent of bone
      infection that will help the surgeon to determine areas of debridement before
      surgery.

PMID- 7586877
TI  - Correlation of Tc-99m GSA hepatic studies with biopsies in patients with chronic
      active hepatitis.
AB  - To determine whether scintigraphic findings of Tc-99m DTPA-galactosyl-HSA (GSA)
      correspond to histopathologic findings, Tc-99m GSA hepatic scintigraphy and
      biopsy were compared in 65 patients with chronic active hepatitis. After
      injecting 185 MBq of Tc-99m GSA, anterior images were obtained at 5 minutes and
      15 minutes. Scintigrams were classified into three grades according to the extent
      of visualization of the cardiac blood pool on 5 minute and 15 minute images.
      Biopsies were subjectively graded for findings of necrosis and fibrosis.
      Scintigraphic grades on 5 minute images were correlated with hepatic necrosis and
      fibrosis and those on 15-minute images with hepatic fibrosis. Scintigraphic
      abnormalities of Tc-99m GSA correlated well with histopathologic abnormalities,
      especially with hepatic fibrosis and necrosis in patients with chronic active
      hepatitis.

PMID- 7586879
TI  - Symmetrical cervical muscle uptake of Ga-67 in Lyme disease.

PMID- 7586878
TI  - Comparison of nuclear bone and gallium scans in the therapeutic evaluation of
      bone lymphoma.
AB  - The objective of this study was to compare Tc-99m MDP bone and Ga-67 scans for
      the therapeutic response to bone lymphoma in 40 patients. The authors
      retrospectively compared 40 Tc-99m MDP bone scans and 20 Ga-67 scans before
      therapy, 29 bone scans and 13 Ga-67 scans during the therapy, and 33 bone scans
      and 15 Ga-67 scans after therapy. Tc-99m MDP and Ga-67 whole body scans were
      obtained within 2 weeks of each study and were graded visually (grades 1-4) in
      which grade 3 means similar count density to that of normal iliac alar activity
      on bone scans and normal liver activity on Ga-67 scans, respectively. The
      findings of lesion improvement during and after therapy were found in 66.0% (19
      of 29) and 72.7% (24 of 33) with Tc-99m MDP bone scans, 84.6% (11 of 13) and
      86.7% (13 of 15) with Ga-67 scans, respectively. The mean grades of Tc-99m MDP
      uptake were 3.06 before, 2.34 during, and 1.75 after therapy. The mean grades of
      Ga-67 uptake were 3.22 before, 1.42 during, and 1.30 after therapy. Ga-67 scans
      appear to be more reliable than Tc-99m MDP bone scans in evaluating the
      therapeutic response of bone lymphoma.

PMID- 7586881
TI  - Another "rim sign". A patent processus vaginalis demonstrated by peritoneal Tc
      99m sc scintigraphy.

PMID- 7586880
TI  - Abnormal uptake of Tc-99m HIG in hematomas.

PMID- 7586882
TI  - Splenosis.

PMID- 7586885
TI  - Tc-99m HMPAO brain SPECT in frontal cortex dysfunction. A case of subcortico
      cortical diaschisis.

PMID- 7586883
TI  - Tc-99m MIBI and TI-201 uptake in a benign thymoma.

PMID- 7586884
TI  - Tc-99m sestamibi uptake by parathyroid carcinoma. False-positive localization of
      parathyroid adenoma.

PMID- 7586886
TI  - Gallium scintigraphy in Lemierre syndrome.

PMID- 7586887
TI  - Incidental detection of thoracic stomach on pertechnetate imaging.

PMID- 7586888
TI  - Detection of adrenal metastasis from osteosarcoma by Tc-99m MDP scintigraphy.

PMID- 7586889
TI  - Anastomotic leak of pancreatic transplant demonstrated by radionuclide
      cystography.

PMID- 7586891
TI  - Unusual presentation of focal nodular hyperplasia.

PMID- 7586890
TI  - Detection of unsuspected metastasis in a melanoma patient with positron emission
      tomography.

PMID- 7586893
TI  - Current readings in nuclear medicine.

PMID- 7586892
TI  - Gastrointestinal uptake of Tc-99m HMDP caused by calcium gluconate.

PMID- 7586894
TI  - Novel delivery of antiarrhythmic agents.
AB  - Conventional antiarrhythmia therapy by oral or intravenous routes of
      administration is often ineffective and results in drug-associated complications
      and toxicity. In addition, poor bioavailability and a high first-pass effect
      limit therapeutic applications of several investigational antiarrhythmic
      compounds, which are otherwise more potent and less toxic than available agents.
      The regional nature of the several cardiac diseases, such as ischaemia,
      restenosis or heart valve calcification, may require a high concentration of drug
      at the location of the disease, which by conventional routes may not be
      attainable due to systemic toxicity of the drug. Localised cardiac delivery of
      antiarrhythmic agents, based on drug-polymer implants, may have several
      advantages, including enhanced drug effects and reduced systemic drug toxicity.
      Computer-assisted automated feedback systems may further enhance the usefulness
      of this therapy in the clinical setting. Before clinical application of this
      method of drug delivery further study will be required, but it is hypothesised
      that pharmacokinetic variability for drugs delivered in this manner will be
      reduced and therefore efficacy and toxicity will be more predictable.

PMID- 7586896
TI  - The role of therapeutic drug monitoring in improving the cost effectiveness of
      anticonvulsant therapy.
AB  - When monitoring of the plasma concentrations of anticonvulsant drugs first came
      into use 25 years ago, it appeared to have a major impact on improving the
      effectiveness and safety of anticonvulsant therapy. However, as time has passed,
      prescribers have absorbed many of the lessons to be learned from the monitoring,
      and now apply this knowledge without necessarily monitoring plasma anticonvulsant
      concentrations as frequently as in the past. Therefore, the effect of the drug
      concentration monitoring on the cost effectiveness of anticonvulsant therapy is
      probably not as significant now as it originally was. In theory, drug
      concentration monitoring is often unlikely to decrease the cost of contemporary
      anticonvulsant drug therapy, but it may enhance the efficacy of the therapy.
      Thus, monitoring may reveal unrecognised under- or overdosage, detect failure of
      compliance or drug-drug interactions, or indicate when there is little point in
      persisting with a particular anticonvulsant drug. Despite a good deal of
      anecdotal testimony, surprisingly little has been published demonstrating the
      benefits of anticonvulsant therapeutic drug monitoring in epileptic populations.
      However, one study did show better rates of seizure control rates in patients
      monitored in the first 6 months of their epileptic disorder; but not if the
      monitoring began later than this.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586895
TI  - Clinical pharmacokinetics in patients with burns.
AB  - Burn injury induces many different pathological changes in the human body, which
      potentially alter pharmacokinetic parameters such as bioavailability, protein
      binding, volume of distribution (Vd) and clearance. The extent of these
      alterations depends on the drug, the type and extent of injury and the time that
      elapsed between injury and drug administration. Bioavailability of large and
      hydrophilic molecules may be increased because of enhanced intestinal
      permeability. The free fraction of a drug in plasma can be increased (when
      primarily bound to albumin) or decreased (when primarily bound to alpha 1-acid
      glycoprotein). Vd may change as a consequence of altered protein binding or an
      enlarged extracellular fluid volume. Alterations in clearance may be due to
      changes in glomerular filtration, tubular secretion, hepatic blood flow, drug
      metabolising activity, protein binding and to the presence of additional
      elimination pathways. Elimination half-life changes when Vd and/or clearance is
      affected following burn injury. The therapeutic consequences of pharmacokinetic
      alterations are discussed in principle, and for specific treatment with
      antibacterials, anti-ulcer drugs, analgesics, muscle relaxants, anxiolytics,
      phenytoin and cyclosporin. If significant changes in pharmacokinetic disposition
      occur following thermal injury, therapeutic drug monitoring and dosage adjustment
      may be required to ensure rational and well tolerated drug therapy in patients
      with burns. Future studies should focus on the impact of specific patient
      variables (e.g. type of injury and size of burn) on the extent of pharmacokinetic
      alterations.

PMID- 7586897
TI  - Local antibacterial therapy for the management of orthopaedic infections.
      Pharmacokinetic considerations.
AB  - Bone infection has long been a formidable foe of orthopaedic surgeons. The
      standard method of treating osteomyelitis generally consists of irrigation and
      debridement supplemented by pre- and postoperative antibiotics and intraoperative
      antimicrobial solutions. In the 1970s, Buchholz introduced the concept of local
      antibacterial therapy in the form of antibiotic impregnated bone cement to
      treated infected arthroplasties. From this, antibiotic impregnated beads were
      developed to treat local infections of bone and soft tissue. The advantage of
      these beads compared with parenteral therapy is that they deliver a high
      concentration of antibacterial locally while avoiding high systemic
      concentrations, thus avoiding adverse effects that are often associated with
      parenteral antibacterial therapy. Additionally, methylmethacrylate bone cement
      does not significantly affect the immune response of the body. This makes the use
      of antibiotic-impregnated polymethylmethacrylate (PMMA) beads highly effective
      either as an alternative to, or in conjunction with, systemic antibiotic
      treatment of infected arthroplasties, and localised bone and soft tissue
      infection. This article explores the indications for the use of local therapy as
      well as any advantages or disadvantages it may have over systemic antibacterial
      treatment. Additionally, there are important pharmacokinetic considerations for
      the optimal use of antibacterial agents in the treatment of osteomyelitis.

PMID- 7586899
TI  - Clinical pharmacokinetics and efficacy of renin inhibitors.
AB  - The successful introduction of angiotensin converting enzyme (ACE) inhibitors in
      the treatment of patients with essential hypertension or heart failure has
      increased interest in the (patho)physiological role of the renin-angiotensin
      system (RAS). ACE is not only involved in the formation of angiotensin II from
      angiotensin I, but also inactivates vasoactive substances such as bradykinin and
      substance P. Accumulation of these substances during treatment with ACE
      inhibitors may contribute to both their therapeutic action and certain adverse
      effects associated with their use, such as cough and angioneurotic oedema. Renin
      inhibitors offer an alternative approach to inhibit the RAS. The major advantage
      of these, still experimental, drugs is their high specificity for the RAS since
      angiotensinogen is the only known substrate of renin. The currently available
      renin inhibitors are pseudopeptides that are rapidly taken up by the liver and
      excreted in the bile. Consequently, these drugs are subjected to a considerable
      first pass effect which limits their oral bioavailability. Additionally, plasma
      elimination half-life times are short and the duration of action is limited.
      Despite these shortcomings, single oral or intravenous administration results in
      a 80 to 90% inhibition of plasma renin activity and a slight reduction in blood
      pressure in patients with hypertension. The extent of blood pressure reduction is
      dependent on the patient's salt balance. After 1 week of oral treatment with the
      renin inhibitor remikiren, the antihypertensive effect was reduced in salt
      repleted hypertensive patients. Subsequent intravenous administration of the drug
      did not further affect blood pressure, indicating that it was not the first pass
      effect that was limiting the efficacy of remikiren.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7586900
TI  - Clinical pharmacokinetics of drugs for Alzheimer's disease.
AB  - Pharmacological treatment of patients with Alzheimer's disease is becoming more
      important, as evidenced by the number of drugs being developed in different
      countries. It has been shown in the majority of clinical trials that
      cholinesterase inhibitors, such as tacrine (tetrahydroaminoacridine), are able to
      induce beneficial effects in cognition and memory. Tacrine, like most of the
      other oral antidementia agents, is rapidly absorbed from the gastrointestinal
      tract. It is excreted mainly through the kidney, with a terminal elimination half
      life of about 3 hours. Tacrine has nonlinear pharmacokinetics and there are large
      interindividual differences in pharmacokinetic parameters after oral, intravenous
      and rectal administration. A positive relationship between cognitive changes and
      plasma tacrine concentrations has been recently described. Similarly, velnacrine
      exhibits evidence of nonlinearity in some pharmacokinetic parameters, but renal
      excretion is a minor route of elimination for this drug. Pharmacokinetic data
      pertaining to eptastigmine, a third cholinesterase inhibitor, is more limited.
      However, the drug is rapidly distributed to the tissues after oral administration
      and readily enters the central nervous system, where it can be expected to
      effectively inhibit acetylcholinesterase in the brain for a prolonged period.
      Pharmacokinetic data for the nootropic agents are more limited. However, of the 3
      agents reviewed only pramiracetam penetrates the central nervous system (CNS)
      poorly. Indeed, oxiracetam crosses the blood-brain barrier and persists for
      longer in the CNS than in the serum. Selegiline (deprenyl), a neuroprotective
      agent, is readily absorbed from gastrointestinal tract. It is metabolised mainly
      in the liver, and to a minimal extent in the lung or kidneys. The steady-state
      concentrations of metabolites in the cerebrospinal fluid (CSF) and serum are very
      similar, reflecting their easy penetration into the CNS. Idebenone, another
      neuroprotective agent, likewise is rapidly absorbed and achieves peak
      concentrations in the brain comparable to those in plasma. Similarly, CSF
      concentrations of metabolites of ST 200 (acetyl-L-carnitine) parallel those in
      plasma, suggesting that they easily cross the blood-brain-barrier. Gangliosides
      (GM1) can be given intramuscularly or subcutaneously, but the latter route of
      administration provides a concentration 50% higher both in the serum and the
      ganglioside fraction. However, because of its longer elimination, the
      intramuscular route is the best form of administration when the brain is the
      target organ for the treatment. Absorption of nimodipine is quite rapid. The
      pharmacokinetics of nimodipine during multiple-dose treatment have not been
      studied extensively; however, the drug does not appear to accumulate during
      repeated administration of standard doses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7586898
TI  - Pharmacokinetic optimisation of antiretroviral therapy in patients with HIV
      infection.
AB  - More than 7 years after the introduction of zidovudine for treatment of HIV
      infection, little use has been made of the pharmacokinetic properties of this or
      any of the subsequently approved antiretroviral agents to optimise therapy. This
      is partly because of the limits of technologies developed to measure clinically
      relevant forms and concentrations of these drugs, and partly because the clinical
      community has been slow to recognise the potential benefits of pharmacokinetic
      optimisation of nucleoside analogue therapy in any disease. Nonetheless, for some
      of these agents, progress in understanding the relationship between
      pharmacokinetics and pharmacodynamics has been made. With zidovudine, for
      example, even though plasma concentrations have little clinical utility, evidence
      suggests that concentrations of active phosphorylated forms of zidovudine inside
      target cells are related to disease progression and toxicity. Furthermore, a
      decreased ability to phosphorylate zidovudine might be a prerequisite for the
      emergence of zidovudine-resistant HIV strains. Measurements of phosphorylated
      zidovudine inside cells similarly suggest that 100 mg of oral zidovudine every 8
      hours approximates the optimal initial dosage regimen in asymptomatic patients.
      Increased plasma didanosine concentrations have been associated with several
      measures of clinical improvement in patients, and may be associated with an
      increased risk of toxicity as well. For zalcitabine and stavudine, however, the
      picture is much less clear. Their pharmacokinetic and pharmacodynamic
      relationships have not been studied in patients. Furthermore, there is
      insufficient data on the effects of age, gender, race and concurrent underlying
      conditions on the pharmacokinetics of all of these agents. Mounting evidence
      suggests that monitoring of these compounds could lead to individually optimised
      intervention strategies. Given the marginal benefits of therapy with these
      agents, their proven toxic effects and the lack of proven alternatives, it is
      critical that the clinical community strive to make the most effective use of
      these agents in the treatment of their patients.

PMID- 7586903
TI  - Remifentanil pharmacokinetics and pharmacodynamics. A preliminary appraisal.
AB  - Remifentanil is a novel, short-acting mu-receptor opioid agonist currently in the
      late stages of development. A member of the 4-anilidopiperidine class, it is
      unique among the currently marketed agents because of its ester structure.
      Remifentanil undergoes widespread extrahepatic metabolism by blood and tissue
      nonspecific esterases, resulting in an extremely rapid clearance of approximately
      3 L/min (180 L/h). Like the other members of this class of drugs, remifentanil is
      lipophilic and is widely distributed in body tissues with a steady-state volume
      of distribution of approximately 30L. Because of its unique metabolic pathway
      (among this group of drugs) and rapid clearance, remifentanil represents a new
      pharmacokinetic class of opioid. Unlike the other fentanyl congeners, termination
      of the therapeutic effect of remifentanil mostly depends on metabolic clearance
      rather than on redistribution. The context-sensitive half-time [defined as the
      time necessary to achieve a 50% decrease in blood (or plasma) concentration after
      termination of a variable-length, continuous infusion targeted to maintain a
      steady-state concentration, where the 'context' is the duration of the infusion]
      is strikingly short for remifentanil, and this is perhaps the most compelling
      evidence of the pharmacokinetic singularity of the drug. Determined by computer
      simulation, the context-sensitive half-time of remifentanil is approximately 3
      minutes, and is independent of infusion duration. Pharmacodynamically,
      remifentanil is similar to the other fentanyl congeners. The drug produces
      physiological changes consistent with potent mu-receptor agonist activity,
      including analgesia and sedation. Its adverse effect profile (like that of the
      other drugs of this class) includes ventilatory depression, nausea, vomiting,
      muscular rigidity, bradycardia and pruritus. Because it does not release
      histamine upon injection, remifentanil has fewer haemodynamic adverse effects
      than morphine. The therapeutic potency of remifentanil is somewhat less than that
      of fentanyl, with an effective concentration (producing 50% of maximal effect, as
      measured by electroencephalography) of approximately 15 to 20 micrograms/L. Speed
      of onset of effect is very rapid and is similar to that of alfentanil, which is
      reflected in a t1/2ke0 (a parameter used to characterise the delay between peak
      blood drug concentration and peak pharmacodynamic effect utilising a theoretical
      effect compartment) of approximately 1 to 2 minutes. Remifentanil is likely to be
      a welcome addition to the anaesthesia drug formulary. Anaesthetists have long
      recognised the need for a short-acting opioid with a predictable pharmacokinetic
      profile.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7586904
TI  - Ondansetron clinical pharmacokinetics.
AB  - Ondansetron is a potent and highly selective serotonin 5-HT3-receptor antagonist
      which has demonstrated important antiemetic activity and good tolerability in the
      prevention of chemotherapy-induced nausea and vomiting. Ondansetron is completely
      and rapidly absorbed from the gastrointestinal tract after oral administration,
      and does not accumulate with repeated oral administration. Owing to hepatic first
      pass metabolism, its bioavailability is only about 60% compared with ondansetron
      administered by infusion over 15 minutes. Bioavailability is slightly increased
      when administered after a standard meal, and is not influenced by
      coadministration of antacids; a slightly enhanced bioavailability has been
      observed in patients with cancer. Since the time to reach peak concentration is
      0.5 to 2 hours after oral ingestion, the drug should be administered at least 30
      minutes before chemotherapy. Possible alternative ways of administration of
      ondansetron include intramuscular, subcutaneous and rectal administration, and
      oral controlled-release formulations. Ondansetron is widely distributed (volume
      of distribution approximately 160L) and binds moderately (70 to 76%) to plasma
      proteins; the elimination half-life averages approximately 3.8 +/- 1 hours.
      Clearance occurs by hepatic metabolism (95%) rather than renal excretion.
      Metabolites do not play a role in the activity of the drug, and there is no
      evidence of genetic polymorphic metabolism. Although aging is associated with
      decreased clearance and increased bioavailability, dosage adjustments are not
      required for the elderly, and may be necessary only in patients with severe
      hepatic impairment. Chemotherapeutic agents do not seem to modify the
      pharmacokinetics of ondansetron. There remains the question of whether control of
      emesis is related to systemic availability of ondansetron and, in consequence,
      the optimal dose and schedule of ondansetron is still to be identified with
      certainty.

PMID- 7586905
TI  - Infant sleep position and the sudden infant death syndrome. A survey of pediatric
      recommendations.
AB  - A questionnaire survey was conducted to assess the impact of the April 1992
      American Academy of Pediatrics Task Force Statement, "Infant Positioning and
      SIDS," on the routine advice provided by pediatricians in Minnesota to families
      with newborn infants regarding sleep practices, including sleep position. There
      was a trend toward more discussion between all pediatric practice groups and
      families regarding infant sleep practices following the AAP Sleep Position
      Statement (P < 0.001-0.003). Prone sleep recommendations ranged from 9.2% for
      newborn infants to 21.4% for infants 6 months of age. Recommendations for the
      supine or lateral sleep positions predominated at all infant ages. Pediatricians
      in private practice were more likely to identify the AAP Statement as
      establishing a medicolegal standard (P < 0.05). We conclude that the 1992 AAP
      Statement has had a significant impact on the routine advice provided to families
      regarding infant sleep practices, including infant sleep position.

PMID- 7586902
TI  - The backpropagation neural network--a Bayesian classifier. Introduction and
      applicability to pharmacokinetics.

PMID- 7586906
TI  - The timing of SIDS deaths in premature infants in an urban population.
AB  - Previous reports have demonstrated that premature infants are at greatly
      increased risk for sudden infant death syndrome (SIDS). Although only 9% of
      infants are born at less than 36 weeks' gestation, 20% of SIDS victims are former
      premature infants. The objective of this study was to characterize the time
      course of SIDS in premature infants and to determine why SIDS occurs at such a
      high rate in this patient population. A database of all cases of SIDS in
      Philadelphia from 1987 through 1991 was used to establish the time course for
      SIDS deaths in term and preterm infants. Gestational age was established by
      Dubowitz exam. To evaluate distinctly different age groups, infants from 32-36
      weeks were excluded from analysis. Age at death and postconceptional age of death
      were compared for both groups. Data are described in weeks (mean +/- SEM), and
      analyzed using unpaired t-test and log-rank test to compare survival rate between
      term and preterm infants. A significant difference (P < 0.01) was noted in age at
      death of term versus preterm infants. No difference was found in postconceptional
      age of death. The survival rates were also different (P < 0.001). Preterm infants
      showed a much wider distribution in age of death from SIDS. The term infants
      followed the classic SIDS curve. By 32 weeks' postnatal age, 95% of all SIDS had
      taken place in the term group, but only 75% in the preterm group. The age at
      death for SIDS differs in the preterm infant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586901
TI  - Clinical pharmacokinetics of various topical ophthalmic delivery systems.
AB  - The eye provides an interesting study in contrasts: it is a delicate structure
      with a transparent anterior wall as thin as 0.5mm; yet this structure in
      combination with the ocular adnexa provides a resilient physicochemical barrier.
      The lids, tears and lacrimal apparatus work in concert to continuously protect
      the cornea and conjunctiva with a stable tear film, which also serves as the
      primary refracting surface. This elaborate defence system simultaneously prevents
      ready intraocular access of pharmaceutical agents. Additionally, the trilaminate
      structure of the cornea has variable permeability to chemical agents, thereby
      further limiting the passage of highly hydrophobic and hydrophilic moieties.
      Presenting topical pharmaceutical agents to the eye via different delivery
      systems allows clinicians to directly affect the profile of drug bioavailability
      and, ultimately, bioactivity. While achieving optimum bioavailability is
      therapeutically important, one must simultaneously limit the occurrence of drug
      induced adverse effects, both systemic and local. Utilising the different
      pharmacokinetic properties of drug delivery systems permits clinicians to
      maximise their therapeutic plans for addressing specific clinical situations
      while minimising the potential for adverse drug effects.

PMID- 7586907
TI  - The management of prepubertal children with gonorrhea.
AB  - To determine whether test-of-cure cultures are necessary for prepubertal children
      diagnosed with Neisseria gonorrhoeae, we examined the records of all 66 patients
      < 10 years old seen at Children's Hospital of Philadelphia over a 7.5-year period
      (1987-1994) diagnosed with gonorrhea. Ninety-eight percent had genital discharge
      on examination. All children with genital gonorrhea were symptomatic, but only
      10% of children with rectal gonorrhea and 20% with pharyngeal infection were
      symptomatic. Seventy-seven percent of children were treated with ceftriaxone. Of
      these, 72% returned for test-of-cure cultures. Ninety-three percent of children
      had complete resolution of physical symptoms at test-of-cure, and all follow-up
      cultures were negative for N. gonorrhoeae. Our data suggest that most prepubertal
      children with gonorrhea are symptomatic at initial presentation and are cured
      after recommended treatment with ceftriaxone. The Centers for Disease Control and
      Prevention recommendations for obtaining test-of-cure cultures in young children
      with gonorrhea are unnecessary, potentially harmful, and should be revised.

PMID- 7586909
TI  - Time of onset of necrotizing enterocolitis in newborn infants with known prenatal
      cocaine exposure.
AB  - Cocaine exposure can lead to diminished gut-blood supply and thereby contribute
      to the pathogenesis of necrotizing enterocolitis (NEC). Investigating the
      hypothesis that NEC occurs at a younger age in cocaine-exposed infants, we
      reviewed 1,284 neonatal intensive care admissions. Infants with NEC were divided
      into cocaine-exposed and cocaine-nonexposed groups, each subdivided into two
      birth-weight groups, using 1,500 g as the cutoff weight. Time of onset of NEC for
      each infant was determined and survival curves for the cocaine-exposed and
      nonexposed groups were calculated using their birth-weight subdivision. Hazard
      function curves were done. Neonatal risk factors in both groups were compared.
      Twelve percent (28/231) of cocaine-exposed infants developed NEC stage II or III
      versus 3% (34/1053) in the nonexposed group (P < 0.05). Eight percent of cocaine
      exposed and 2% of nonexposed survivors had NEC by day 7 versus 20% and 5% by day
      28 after birth (P < 0.05). Infants > 1,500 g were at risk for NEC until day 8
      only, whereas infants < or = 1,500 g had both an early and continuing risk for
      NEC with a biphasic pattern of onset. The accentuated peak in early-onset NEC may
      be attributed to antenatal cocaine exposure, while late-onset NEC in the < or =
      1,500 g group probably relates to a variety of pathogenetic factors.

PMID- 7586908
TI  - Gonococcal and chlamydial genitourinary infections in symptomatic and
      asymptomatic adolescent women.
AB  - To determine the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae
      endocervical infections in a group of adolescent women, gynecologic histories and
      evaluations were done on symptomatic and asymptomatic adolescent women presenting
      for pelvic examinations in an urban, hospital-based, adolescent clinic. C.
      trachomatis and N. gonorrhoeae cultures and three nonculture diagnostic tests for
      chlamydia (two ELISA assays and one DNA-probe) were performed on each patient.
      Patients were 12 to 21 years of age (mean 17.0); 53% were African-American, and
      47% were Caucasian. Two hundred twenty-eight women were asymptomatic and 249
      women had symptoms. There were 64 cases of chlamydia and 19 cases of gonorrhea;
      an additional 11 patients had both chlamydia and gonorrhea. Approximately one
      third of patients with chlamydia, gonorrhea, or both had asymptomatic disease an
      important reservoir of infection.

PMID- 7586910
TI  - Pediatric fiberoptic bronchoscopy.

PMID- 7586911
TI  - Acute hydrocephalus masquerading as catch-up head growth in an infant with cystic
      fibrosis.

PMID- 7586912
TI  - Hypernatremic dehydration and rotavirus enteritis.

PMID- 7586913
TI  - Neurogenic pulmonary edema associated with pneumococcal meningitis.

PMID- 7586914
TI  - Necrotizing pancreatitis after 10 years of therapy with valproic acid.

PMID- 7586915
TI  - The case of Baby L revisited.

PMID- 7586916
TI  - The role of serology in the diagnosis of Helicobacter pylori infection in
      children.
AB  - The aim of this study was to evaluate the diagnostic accuracy of serologic tests
      and to verify whether specific IgG antibody can be used in the diagnosis of
      Helicobacter pylori infection in children without endoscopy. Serologic and
      endoscopic examinations were performed in 310 children (1 month-15 years) with
      gastrointestinal symptoms. Serologic outcomes were compared with the results of
      rapid urease test, histologic examination, and culture. The prevalence of H.
      pylori infection was 21.0% and the seropositivity of H. pylori was 24.2% in these
      symptomatic children. Serologic examination for diagnosis of H. pylori showed a
      sensitivity of 94.9% and a specificity of 92.4%, diagnostic reliability equal to
      the rapid urease test and histologic examination in children. The serum IgG test
      is a useful tool for the diagnosis of H. pylori infection, especially in
      children.

PMID- 7586917
TI  - Helicobacter pylori disease in childhood.

PMID- 7586918
TI  - Factors associated with improved immunization rates for urban minority preschool
      children.
AB  - Urban, poor, preschool children are noted for having low immunization rates. To
      determine factors related to completion of immunization, vaccine records of 479 3
      year-old children from an inner-city pediatric clinic were reviewed. Complete
      immunization was defined as four diphtheria-tetanus-pertussis doses, three oral
      polio vaccine doses, one measles-mumps-rubella dose, and one Haemophilus
      influenzae type b vaccine dose. Seventy percent of our patients were up-to-date
      by 2 years of age. The administration of all age-appropriate vaccines at a single
      visit for patients 15 months and older, the establishment of a continuous primary
      care relationship, earlier age at first immunization, and lower birth weight were
      significantly associated with higher immunization levels in our study.

PMID- 7586919
TI  - Congenital diaphragmatic hernia. Outcome of preoperative extracorporeal membrane
      oxygenation.
AB  - In recent years, increasing numbers of patients with congenital diaphragmatic
      hernia (CDH) have been offered extracorporeal membrane oxygenation (ECMO)
      preoperatively if they can not physiologically tolerate early surgical repair.
      These infants are sicker are more unstable than those repaired pre-ECMO and, in
      most cases, have not had a "honeymoon" period (i.e., PaO2>100 mm Hg at some
      point). ECMO before surgical repair was offered to 27 CDH patients in our
      institution; of the 16 (59%) survivors, 11 are now 2 years of age to older. To
      determine the outcome risk for this critical population, we compared 11 infants
      placed on ECMO pre-CDH repair (Group A) with our previous series of 22 survivors
      who had their surgery prior to ECMO (Group B). Both groups were similar in birth
      weight, gestational age, and Apgar scores. In Group A, a greater number were
      females (73% vs 23%), had right-sided hernia (64% vs 23%), and required patch
      repairs (82% vs 23%). The mean time on ECMO, time to extubation, and mean length
      of hospitalization were longer in group A. In both groups combined, the frequency
      of reherniation was higher in the patch-repair infants compared with those with a
      primary closure. Incidence of reflux was high in both groups, with increasing
      frequency of Nissen fundoplication in Group A patients (45% vs 6%). Both groups
      demonstrated similar delayed growth at 1 year of age. Although infants placed on
      ECMO presurgery are sicker, with more post-ECMO morbidity, their growth failure
      is similar to the less sick infants repaired pre-ECMO.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7586920
TI  - Intravenous theophylline in pediatric status asthmaticus. A prospective,
      randomized, double-blind, placebo-controlled trial.
AB  - This study was conducted to determine whether intravenous theophylline, added to
      inhaled albuterol and intravenous methylprednisolone, provides a clinically
      significant benefit in the treatment of pediatric status asthmaticus. Patients
      aged 2 to 10 years were randomized to receive either intravenous theophylline or
      placebo. All patients received aerosolized albuterol and intravenous
      methylprednisolone. There was no difference between groups in the improvement of
      a clinical asthma score over time, in oxygen requirement, or in the number of
      albuterol treatments required. Theophylline group patients experienced more
      nausea, emesis, and insomnia. We conclude that there is no benefit in adding
      theophylline to treatment with methylprednisolone and albuterol for pediatric
      status asthmaticus. Furthermore, there are significantly more adverse effects
      associated with the use of theophylline.

PMID- 7586921
TI  - Congenital midline nasofrontal mass. Two case reports with a clinical review.
AB  - Because of aberrant embryologic development, encephalocele, nasal dermoid, and
      glioma may present as a nasofrontal midline mass in a newborn infant. Though
      uncommon, vascular malformation or hemangioma in the nasofrontal region may
      present similarly. The correct diagnosis and early management of a nasofrontal
      mass is imperative because complications such as brain herniation, hypertelorism,
      or cerebrospinal fluid rhinorrhea may ensue, resulting in poor facial or visual
      development, recurrent meningitis, and brain abscess. Nasofrontal encephalocele
      and midline frontal vascular malformation are rare congenital abnormalities
      presenting as a midline nasofrontal mass. We report two neonatal cases, one a
      frontoethmoidal encephalocele and another, a frontal vascular malformation. Both
      had uncomplicated surgical interventions. The physical findings and clinical
      review are presented. The diagnostic approach toward midline nasofrontal mass is
      discussed.

PMID- 7586922
TI  - Acute childhood immune thrombocytopenic purpura. Diagnosis and treatment.

PMID- 7586923
TI  - Traumatic epiglottis following blind finger sweep to remove a pharyngeal foreign
      body.

PMID- 7586926
TI  - Ascending cord necrosis. Complication of intrathecal chemotherapy with radiologic
      pathologic correlation.

PMID- 7586924
TI  - Lead screening in children with attention deficit hyperactivity disorder and
      developmental delay.

PMID- 7586925
TI  - Primary sclerosing cholangitis and multiple autoimmune disorders in a patient
      with Down syndrome.

PMID- 7586927
TI  - The fate of naringin in humans: a key to grapefruit juice-drug interactions?
AB  - The increase of concentrations observed for many drugs when administered
      concomitantly with grapefruit juice was attributed to inhibition of cytochrome
      P450 enzymes by naringenin, the aglycone of the grapefruit flavonoid naringin.
      However, this explanation is equivocal, and formation of naringenin after
      ingestion of grapefruit juice has not been proved. We investigated renal
      excretion of naringin, naringenin, and its glucuronides after administration of
      20 ml grapefruit juice (621 mumol/L naringin) per kilogram of body weight to six
      healthy adults. Urine was collected for 24 hours, and flavonoids were measured by
      HPLC in aliquots with and without glucuronidase pretreatment. Naringin or
      naringin glucuronides were not found. Naringenin and its glucuronides appeared in
      urine after a median lag-time of 2 hours and reached 0.012% to 0.37% and 5.0% to
      57%, respectively, of the molar naringin dose. In additional investigations, low
      concentrations (< 4 mumol/L) of naringenin glucuronides, but neither naringin nor
      naringenin were found in plasma samples from previous grapefruit juice
      interaction studies, and metabolization of naringin to naringenin occurred during
      24 hours of incubation (37 degrees C) in three of five feces samples tested. The
      data suggest that cleavage of the sugar moiety, presumably by intestinal
      bacteria, is the first step of naringin metabolism. Naringenin formation is
      thought to be the crucial step in determination of bioavailability of the
      compound, which undergoes rapid glucuronidation. The pronounced interindividual
      variability of naringin kinetics provides a possible explanation for some of the
      apparently contradictory results of drug interaction studies with grapefruit and
      naringin.

PMID- 7586928
TI  - Dihydrocodeine: a new opioid substrate for the polymorphic CYP2D6 in humans.
AB  - BACKGROUND: The opioid dihydrocodeine (DHC) is frequently used as an analgesic
      and antitussive agent. However, until now there have been no detailed data on
      dihydrocodeine metabolism in humans. We therefore investigated pathways that
      contribute to elimination of dihydrocodeine, and we tested the hypothesis that
      dihydrocodeine O-demethylation to dihydromorphine (DHM) is catalyzed by the
      polymorphic CYP2D6. METHODS: A single oral dose of dihydrocodeine was
      administered to six extensive (metabolic ratio [MR] < or = 1), two intermediate
      (1 < MR < 20) and six poor metabolizers (MR > or = 20) of sparteine/debrisoquin.
      Serum concentrations of dihydrocodeine and dihydromorphine were measured up to 25
      hours, and urinary excretion of conjugated and unconjugated dihydrocodeine,
      dihydromorphine, and nordihydrocodeine were determined. RESULTS: There were no
      differences in the pharmacokinetics of dihydrocodeine between extensive and poor
      metabolizers. However, the area under the serum concentration-time curve (AUC),
      partial metabolic clearance, and total urinary recovery of dihydromorphine were
      significantly lower in poor metabolizers (10.3 +/- 6.1 nmol.hr/L; 7.0 +/- 4.1
      ml/min; 1.3% +/- 0.9% of dose) compared with extensive metabolizers (75.5 +/-
      42.9 nmol.hr/L; 49.7 +/- 29.9 ml/min; 8.9% +/- 6.2%; p < 0.01). There was a
      strong correlation between the AUCDHC/AUCDHM ratio and the urinary metabolic
      ratio of sparteine (rS = 0.89, p = 0.001). No significant differences between
      extensive and poor metabolizers were detected in urine for conjugated
      dihydrocodeine (extensive metabolizers, 27.7% of dose; poor metabolizers, 31.5%),
      unconjugated dihydrocodeine (extensive metabolizers, 31.1%; poor metabolizers,
      31.1%), conjugated nordihydrocodeine (extensive metabolizers, 6.3%; poor
      metabolizers, 5.4%), or unconjugated nordihydrocodeine (extensive metabolizers,
      15.8%; poor metabolizers, 19.5%). CONCLUSIONS: Dihydrocodeine O-demethylation to
      dihydromorphine is impaired in poor metabolizers of sparteine. The main urinary
      metabolites after administration of dihydrocodeine are the parent compound and
      its conjugates in extensive and poor metabolizers.

PMID- 7586929
TI  - Effects of felbamate on the pharmacokinetics of the monohydroxy and dihydroxy
      metabolites of oxcarbazepine.
AB  - The effects of felbamate on the multiple dose pharmacokinetics of the monohydroxy
      and dihydroxy metabolites of oxcarbazepine were assessed in a placebo-controlled,
      randomized, double-blind crossover study in 18 healthy male volunteers.
      Oxcarbazepine, 1200 mg/day, was administered on an open basis in combination with
      double-blind placebo or 2400 mg/day felbamate for two 10-day treatment periods
      separated by a 14-day washout period. Pharmacokinetic parameters of
      monohydroxyoxcarbazepine and dihydroxyoxcarbazepine were determined from plasma
      and urine samples obtained on the tenth day of each treatment period. Felbamate
      had no effect on monohydroxyoxcarbazepine plasma or urine pharmacokinetics
      compared with placebo, but it significantly increased values for
      dihydroxyoxcarbazepine maximum concentration and area under the curve from 0 to
      12 hours, as well as urinary excretion of free and total dihydroxyoxcarbazepine.
      The mechanism that may account for the observations is the induction of oxidative
      metabolism of monohydroxyoxcarbazepine. Despite these changes, the relative
      amount of dihydroxyoxcarbazepine is small in comparison to
      monohydroxyoxcarbazepine, and antiepileptic activity is associated with
      monohydroxyoxcarbazepine rather than dihydroxyoxcarbazepine. Therefore we
      conclude that felbamate has no clinically relevant effects on the
      pharmacokinetics of oxcarbazepine in humans.

PMID- 7586930
TI  - Single- and multiple-dose pharmacokinetics of nefazodone in patients with hepatic
      cirrhosis.
AB  - OBJECTIVE: To compare the single- and multiple-dose pharmacokinetics of
      nefazodone and its three pharmacologically active metabolites, hydroxynefazodone,
      m-chlorophenylpiperazine, and triazoledione, in patients with biopsy-proven
      cirrhosis and age-, sex-, and weight-matched healthy volunteers. METHODS:
      Subjects received a single 100 mg dose of nefazodone on day 1 followed by 100 mg
      nefazodone every 12 hours on days 3 through 10. Serial blood samples were
      collected on days 1 and 10; blood samples for trough levels were also collected
      just before the morning doses on days 7, 8, and 9. Plasma samples were assayed
      for nefazodone and its metabolites by validated chromatographic methods. RESULTS:
      The blood samples for trough levels indicated that, regardless of hepatic
      function, steady state for nefazodone and its metabolites was achieved by the
      fourth day of every-12-hour dosing. Subjects with liver cirrhosis had about a two
      fold greater systemic exposure to nefazodone and hydroxynefazodone compared with
      normal subjects after a single dose of nefazodone, the difference decreasing to
      approximately 25% at steady state. Exposure to m-chlorophenylpiperazine was
      twofold to threefold greater and exposure to triazoledione was similar in
      patients with cirrhosis after a single dose of nefazodone and at steady state.
      There were no serious or unexpected adverse events observed in this study.
      CONCLUSIONS: These findings indicate that, although no untoward accumulation is
      anticipated compared with patients with normal hepatic function, patients with
      hepatic impairment may be exposed to higher concentrations of nefazodone and its
      metabolites than would subjects with normal hepatic function. Consequently, a
      lower daily dose of nefazodone should be considered when treating patients with
      impairment of hepatic function.

PMID- 7586931
TI  - Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans.
AB  - OBJECTIVES: Although fluvoxamine inhibits the biotransformation of drugs known to
      be metabolized by CYP1A2, there are no data available with regard to the
      importance of CYP1A2 for the metabolism of fluvoxamine itself. Because smoking
      induces the metabolism of drugs catalyzed by CYP1A2, this study investigated the
      pharmacokinetics of fluvoxamine in smokers and nonsmokers. METHODS: The serum
      concentration of fluvoxamine was determined by high-performance liquid
      chromatography for 48 hours after oral administration of a single dose of 50 mg
      fluvoxamine to 12 smokers (> or = 10 cigarettes per day) and 12 nonsmokers.
      RESULTS: The smokers had significantly lower areas under the serum concentration
      time curve and significantly lower maximal serum concentrations than the
      nonsmokers (mean +/- SD, 771 +/- 346 versus 1110 +/- 511 nmol.hr.L-1 [p = 0.012]
      and 39.1 +/- 17.3 versus 57.7 +/- 21.5 nmol.L-1 [p = 0.012], respectively). The
      terminal elimination half-life did not differ significantly between smokers and
      nonsmokers (10.1 +/- 1.9 and 10.7 +/- 2.3 hours, respectively). The oral
      clearance was high among both smokers (4.1 +/- 1.9 L.min-1) and nonsmokers (3.3
      +/- 2.7 L.min-1; difference not significant). CONCLUSION: Smokers had lower serum
      concentrations of fluvoxamine than nonsmokers after a single oral dose of
      fluvoxamine. This finding is consistent with a possible role of CYP1A2 in
      fluvoxamine metabolism.

PMID- 7586932
TI  - Genetic analysis of the S-mephenytoin polymorphism in a Chinese population.
AB  - The 4'-hydroxylation of S-mephenytoin exhibits a polymorphism in humans, with the
      poor metabolizer phenotype exhibiting a lower frequency in white (3% to 5%) than
      in Oriental populations (13% to 23%). Two mutations in CYP2C19 (CYP2C19m1 and
      CYP2C19m2) have recently been described that account for approximately 85% of
      white and 100% of Japanese poor metabolizers. This study examines whether these
      mutations account for the poor metabolizer phenotype in the Chinese population.
      The metabolism of S-mephenytoin exhibited a bimodal distribution in 244 unrelated
      Chinese subjects, although the distribution of the two phenotypes overlapped. In
      75 selected Chinese subjects, CYP2C19 genotype analysis predicted the phenotype
      with 100% accuracy. The frequency of the poor metabolizer phenotype was
      approximately 11% (95% confidence interval 7% to 15%). The frequency of the
      CYP2C19m1 allele was 0.289, whereas that of CYP2C19m2 was 0.044. Homozygous
      extensive metabolizers had slightly lower ratios of S/R-mephenytoin compared with
      heterozygous extensive metabolizers, showing a gene-dosage effect. These data
      show the advantages of genotype analysis in investigations of the mephenytoin
      phenotype in Oriental subjects.

PMID- 7586933
TI  - In vivo inhibition profile of cytochrome P450TB (CYP2C9) by (+/-)-fluvastatin.
AB  - BACKGROUND: (+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme
      A (HMG-CoA) reductase inhibitor that selectively and competitively inhibits
      P450TB (CYP2C9) in vitro. The potential for kinetic interactions in vivo between
      fluvastatin and P450TB substrates was therefore investigated in healthy
      volunteers. METHODS: Diclofenac (25 mg orally) oxidation was used as a marker of
      P450TB activity on days 0, 1, and 8 of fluvastatin treatment (40 mg/day).
      RESULTS: Diclofenac peak concentration (Cmax) increased over time (0.28 [SD,
      0.12], 0.38 [0.20], and 0.45 [0.4] mg/L on days 0, 1, and 8, respectively). Oral
      clearance was reduced on days 1 and 8 (14% and 15%, respectively). A time
      dependent decrease in urinary metabolic ratio (MR, 4'
      hydroxydiclofenac/diclofenac) was noted (1.07 [0.34], 0.90 [0.23] and 0.70 [0.18]
      on days 0, 1, and 8, respectively [p < 0.0001]) for the first 4 hours. The
      interaction was clear in only some individuals; MR reduction was related to
      baseline MR and it was more pronounced in subjects with a higher baseline MR (p <
      0.01). Fluvastatin Cmax (0.18 [0.11] and 0.32 [0.1] mg/L on days 1 and 8,
      respectively) and area under the curve (0.28 [0.12] and 0.43 [0.15] hr.mg/L on
      days 1 and 8, respectively; p < 0.001) increased over time. Diclofenac MR
      reduction was correlated with fluvastatin concentrations. CONCLUSIONS:
      Interactions between fluvastatin and P450TB substrates (phenytoin, oral
      anticoagulants, oral hypoglycemic agents, and nonsteroidal antiinflammatory
      drugs) may occur, at least in some patients.

PMID- 7586934
TI  - Effects of cisplatin on urinary thromboxane B2 excretion.
AB  - PURPOSE: Thromboxane A2 (TxA2) is implicated in the pathogenesis of various forms
      of drug-induced renal damage. Based on previous functional studies, we postulated
      that cis-dichlorodiammineplatinum (cisplatin) induces intrarenal TxA2 synthesis.
      To test this hypothesis, we measured urinary excretion of thromboxane B2 (TxB2),
      the stable inactive metabolite of TxA2, during and after cisplatin
      administration. PATIENTS AND METHODS: The study included 16 patients with
      malignant disease who were scheduled to receive cisplatin (100 mg/m2) and 11
      healthy subjects who received the same amount of fluid loading and the same
      concomitant medication as the patients but no cisplatin. Total urine output was
      collected in seven intervals from 24 hours before until 72 hours after the start
      of prehydration. Urinary immunoreactive TxB2 was measured. RESULTS: There was a
      marked increase (4.5 +/- 1.6-fold; mean +/- SEM) in urinary TxB2 excretion in
      patients during and immediately after cisplatin infusion. This increase was
      significant compared with baseline and the control group. CONCLUSION: High-dose
      cisplatin causes an acute increase in urinary excretion of TxB2. This likely
      represents enhanced intrarenal synthesis of TxA2, in response to an acute
      damaging effect of cisplatin on the kidneys. These findings warrant further
      studies to evaluate the renoprotective effect of anti-TxA2 intervention in
      patients receiving high-dose cisplatin.

PMID- 7586935
TI  - Dietary sodium intake modulates systemic but not forearm norepinephrine release.
AB  - INTRODUCTION: Sodium intake has profound effects on systemic and renal
      sympathetic activity, but its effects on sympathetic activity in skeletal muscle
      vascular beds, a site at which local regulatory mechanisms could alter vascular
      tone directly, are unclear. METHODS: To determine the effect of dietary sodium
      intake on basal and isoproterenol-stimulated systemic and forearm norepinephrine
      kinetics, we studied seven healthy male volunteers twice, 4 weeks apart, while
      they were receiving a low-sodium (10 mmol sodium/24 hours) diet and a high-sodium
      diet (250 mmol sodium/24 hours). Forearm blood flow, measured by plethysmography,
      and systemic and forearm norepinephrine spillover, measured by radioisotope
      dilution, were determined before and after intra-arterial infusion of 60 and 400
      ng/min isoproterenol. RESULTS: Baseline (before isoproterenol) systemic
      norepinephrine spillover was higher when subjects received the low-sodium diet
      (448.1 +/- 55.7 ng/min) compared with the high-sodium diet (269.7 +/- 42.7
      ng/min; p < 0.05). In contrast, sodium intake did not affect local forearm
      norepinephrine spillover, either at baseline (low-sodium diet, 2.05 +/- 0.48
      ng/min versus high-sodium diet, 2.63 +/- 0.79 ng/min; p = 0.50) or after
      stimulation with isoproterenol in doses of 60 ng/min (low-sodium diet, 8.84 +/-
      2.2 ng/min versus high-sodium diet, 6.1 +/- 1.9 ng/min; p = 0.38) or 400 ng/min
      (low-sodium diet, 16.4 +/- 4.5 ng/min versus high-sodium diet, 16.7 +/- 2.5
      ng/min; p = 0.93). CONCLUSIONS: Under conditions of low sodium intake, systemic
      norepinephrine spillover was increased but forearm norepinephrine spillover was
      not, suggesting that alteration in sodium intake may produce a differential
      effect on norepinephrine spillover in different tissues but that decreased local
      sympathetic activity in skeletal muscle is not the likely mechanism by which a
      low-sodium diet may lower blood pressure or attenuate stress-induced pressor
      responses.

PMID- 7586936
TI  - Hemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans.
AB  - OBJECTIVE: The objective of this study was to evaluate the exercise capacity of
      subjects given an autologous transfusion or a polymerized bovine hemoglobin
      solution to define the pharmacodynamics and pharmacokinetics of a new hemoglobin
      based oxygen carrier (HBOC-201). METHODS: Six normal healthy male subjects (ages
      25 to 45 years) participated in this randomized, single-blind, two-way crossover
      study, which took place at Upjohn Research Clinics in Kalamazoo, Mich. A radial
      artery catheter was inserted in each subject before serial cardiac output and
      pulmonary function tests and phlebotomy of 15% blood volume (750 ml plus another
      250 ml for study laboratories yields 1000 ml, or about 150 gm human hemoglobin).
      This was followed by isovolemic hemodilution with Ringer's lactate plus an
      autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine
      hemoglobin of HBOC-201 (or autologous transfusion). Bicycle exercise stress tests
      to anaerobic threshold (approximately 65% of predicted maximum aerobic capacity)
      were done before phlebotomy and at approximately 45 minutes after the autologous
      transfusion or HBOC-201 infusion. RESULTS: Subjects had similar exercise and
      diffusion capacity but lower lactate levels (for up to 24 hours) during HBOC-201
      (which paralleled plasma HBOC-201 levels) than during autologous transfusion
      periods. Oxygen use (uptake) and carbon dioxide production at rest were greater
      during the HBOC-201 infusion than during the autologous transfusion period. The
      half-life of HBOC-201 was about 23 hours. CONCLUSIONS: Exercise capacity and
      diffusion capacity were similar after HBOC-201 and autologous transfusion. HBOC
      201 resulted in greater oxygen (or uptake) and carbon dioxide production and
      lower lactate levels compared with autologous transfusion. Under the conditions
      of the study, the physiologic effects of 1 gm bovine hemoglobin of HBOC-201 were
      similar to 3 gm human hemoglobin from autologous transfusion.

PMID- 7586939
TI  - [Lys(B28), Pro(B29)]-human insulin: effect of injection time on postprandial
      glycemia.
AB  - BACKGROUND: [Lys(B28), Pro(B29)]-human insulin (lispro) is an insulin analogue
      with a reduced capacity for self-association and faster absorption from
      subcutaneous injection sites. We hypothesized that administration of lispro
      closer to a meal would result in better glucose control than that achieved with
      regular insulin. METHODS: This trial used a randomized crossover design that
      consisted of a period of metabolic stabilization lasting 9 days followed by an
      evaluation period lasting 5 days. The patients received weight-maintenance diets,
      and insulin doses were adjusted as needed. Calorie intake, insulin dose, and
      activities were kept constant once the evaluation period began. During the
      evaluation period, we varied the time between insulin injection and mealtime and
      assessed glucose control. RESULTS: During the evaluation period, the lowest mean
      glucose concentrations were 117.9 mg/dl for lispro and 119.8 mg/dl (p = 0.817)
      for regular insulin. To obtain these, we gave lispro, on average, 22.5 minutes
      before meals and regular insulin 63.8 minutes before meals (p = 0.006). A similar
      pattern was evident throughout the glucose control parameters. The exception was
      mean amplitude of glucose excursion, which was lower after lispro (59 versus 75
      mg/dl; p = 0.007) compared with regular insulin. CONCLUSIONS: We achieved equal
      or slightly better glucose control, as reflected by mean amplitude of glucose
      excursion, with insulin lispro given much closer to meal time than that achieved
      with regular insulin. As a result of these findings, we propose that a rapidly
      absorbed analogue of insulin is capable of achieving better control of
      postprandial glucose at a more convenient injection time.

PMID- 7586937
TI  - A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking
      cessation and abstinence in heavy, dependent smokers.
AB  - OBJECTIVE: To assess the effectiveness of moclobemide on smoking cessation and
      abstinence in heavy, dependent smokers. There is a strong association between
      smoking and depression, especially in dependent smokers. It was hypothesized that
      smoking is a self-medication to treat depression. Cigarette smoke has monoamine
      oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non
      smokers. METHODS: We used a randomized, double-blind, placebo-controlled parallel
      group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day
      during the third month, was given. Main outcome measures were self-reported and
      biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate.
      Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression
      Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma
      dihydroxyphenylglycol as a measure of MAO-A activity. RESULTS: Eighty-eight
      smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The
      continuous self-reported abstinence rate was higher with moclobemide than with
      placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05;
      until the end of follow-up, 1 year: p = 0.09). The abstinence rate according to
      plasma cotinine levels showed a trend to effectiveness of moclobemide (end point:
      p = 0.13; follow-up: p = 0.12). Platelet MAO-B activity increased after smoking
      cessation but without a significant difference. Plasma dihydroxyphenylglycol
      levels did not change in the placebo group but decreased dose dependently in the
      moclobemide group. No difference occurred for withdrawal symptoms, Montgomery
      Asberg Depression Rating Scale, and Hamilton anxiety scores. Cessation of
      moclobemide had no adverse effect. More subjects reported insomnia with
      moclobemide (n = 16) than with placebo (n = 3). CONCLUSION: In this preliminary
      study, the reversible, selective MAO inhibitor moclobemide facilitated smoking
      cessation in highly dependent smokers. Further studies with substantially more
      smokers are needed to evaluate the role of MAO inhibitors in smoking cessation
      and abstinence in smokers with high nicotine dependence.

PMID- 7586938
TI  - A comparison of crossover versus parallel-group design in the evaluation of
      analgesic efficacy after molar extraction.
AB  - This study compares the analgesic effects of two standard combinations (Empirin
      with codeine versus Mersyndol) and placebo as measured by crossover versus
      parallel-group design. The analgesic results obtained with three groups of 12 to
      13 crossed over subjects with two extractions divided into six subgroups of five
      to seven subjects for each sequence were qualitatively the same and statistically
      at least as strong as those obtained by analysis of parallel groups of 38 to 42
      extractions per group. By both methods the analgesics were statistically
      significantly more effective than placebo. The difference between the two
      products was not statistically significant, although the score for Mersyndol was
      somewhat better by both methods of study. The crossover data did not allow
      judgments concerning side effects in spite of its greater efficiency in
      quantifying pain relief.

PMID- 7586940
TI  - Association of serum creatinine and age with headache caused by nitrates. Gruppo
      Italiano di Farmacovigilanza nell'Anziano.
AB  - To assess whether serum creatinine and age are associated with headache induced
      by nitrates, 2742 hospitalized patients taking nitrates were studied during their
      hospital stay. Those patients with admission serum creatinine levels from 97 to
      133 mumol/L and > 133 mumol/L were compared with patients with creatinine levels
      < 97 mumol/L. Gender, body mass index, comorbidity, cognitive status, new intake
      of nitrates, number of daily administrations, and daily dosage, as well as intake
      of angiotensin converting enzyme inhibitors, calcium antagonists, diuretics and
      nonsteroidal anti-inflammatory drugs were examined as possible confounders. Fifty
      six patients had headaches that had a causal link with intake of nitrates.
      Compared with the lowest creatinine group, after adjustment for potential
      confounding variables, the odds ratios and 95% confidence interval (95% CI) for
      headache caused by nitrates associated with increasing serum creatinine levels
      were 0.6 (95% CI, 0.3 to 1.1) and 0.2 (95% CI, 0.0 to 1.2), respectively (p for
      trend = 0.013). Increasing age was inversely associated with headache (odds ratio
      for 10-year increase, 0.6 [95% CI, 0.5 to 0.7]). Serum creatinine and age were
      independently and inversely associated with headache caused by nitrates.

PMID- 7586941
TI  - Effects of dietary fat on drug absorption.

PMID- 7586943
TI  - Urinary excretion of 6-hydroxychlorzoxazone as an index of CYP2E1 activity.
AB  - OBJECTIVE: To determine whether the urinary excretion of 6-hydroxychlorzoxazone
      is an index of CYP2E1 activity in vivo. METHODS: Male volunteers (n = 27; age
      range, 17 to 36 years) who were abstinent from alcohol were studied.
      Chlorzoxazone, 500 mg, was given orally and plasma was collected at 31/2, 41/2,
      51/2, and 61/2 hours after dosing. Urine was collected for 8 hours. Ten
      volunteers participated in full kinetic studies to define the absorption phase
      and plasma area under the concentration-time curve of chlorzoxazone and the
      urinary kinetics of the 6-hydroxy metabolite. Chlorzoxazone and the 6-hydroxy
      metabolite were measured by high-performance liquid chromatography. CYP2E1
      activity was expressed as a hydroxylation index (HI = mmole oral chlorzoxazone
      dose/mmole 6-hydroxychlorzoxazone in 8-hour urine). RESULTS: There was a
      significant positive correlation between plasma elimination rate constant for
      chlorzoxazone (Ke) and urinary excretion of the metabolite (n = 27, r = 0.42, p <
      0.03) and a significant negative correlation between plasma Ke and HI (n = 27, r
      = -0.41, p < 0.04). The mean absorption rate constant for chlorzoxazone of 3.11
      +/- 4.67 hr-1 was fivefold greater than the plasma Ke of 0.57 +/- 0.17 hr-1 for
      the full kinetic studies. The formation clearance of the 6-hydroxy metabolite was
      negative between plasma Ke of the parent compound and disposition rate constant
      for urinary excretion of the 6-hydroxy metabolite (n = 15, r = 0.85, p < 0.0001).
      CONCLUSIONS: The urinary excretion of 6-hydroxychlorzoxazone is limited by
      formation rate and may be useful as an in vivo probe of CYP2E1 activity.

PMID- 7586947
TI  - Effect of probenecid on the distribution and elimination of ciprofloxacin in
      humans.
AB  - OBJECTIVE: Probenecid-sensitive anion transport systems may be involved in
      distribution and elimination processes of anionic drugs. The aim of this study
      was to determine the effect of multiple probenecid treatment on the
      pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in
      12 healthy volunteers. METHODS: A single intravenous dose of 200 mg ciprofloxacin
      was given with and without multiple oral administration of probenecid in a
      randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat
      samples were drawn and analyzed for ciprofloxacin and its 2-aminoethylamino
      metabolite (M1) by reversed-phase HPLC. RESULTS: Plasma area under the
      concentration-time curve and elimination half-life of ciprofloxacin were
      increased (p < 0.05), and urinary recovery and total and renal clearance
      decreased (p < 0.05) in the presence of probenecid. Nonrenal clearance and volume
      of distribution did not differ significantly with and without coadministration of
      probenecid. Peak plasma concentration, plasma area under the concentration-time
      curve, and elimination half-life of M1 were increased (p < 0.05) because of the
      higher amount of M1 formed and the reduced renal clearance (p < 0.05) of the
      metabolite. Saliva, tear, and sweat exposure were elevated (p < 0.05), but the
      alterations can be attributed primarily to the different kinetics of
      ciprofloxacin in plasma. CONCLUSIONS: Coadministration of probenecid altered the
      renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite
      kinetics and distribution into saliva, tears, and sweat were affected
      accordingly, but there was no direct effect of probenecid on these processes.
      This type of drug-drug interaction might be of clinical relevance when
      ciprofloxacin is combined with drugs eliminated by the organic anion transport
      system in the kidney tubules.

PMID- 7586942
TI  - Differentiation of absorption and first-pass gut and hepatic metabolism in
      humans: studies with cyclosporine.
AB  - The low and variable bioavailability of cyclosporine has been attributed to poor
      absorption. However, recent studies have suggested that intestinal first-pass
      metabolism exerts a significant effect on bioavailability. We describe theory and
      methods to differentiate the contribution from oral absorption and intestinal and
      hepatic metabolism to overall cyclosporine bioavailability. Analysis of data from
      previous studies in our laboratories shows that in the absence of intestinal
      metabolism, cyclosporine absorption from its presently available dosage form
      averages at least 65% +/- 12% in healthy volunteers and 77% +/- 19% in kidney
      transplant patients. Analysis also suggests that the extraction ratio for
      cyclosporine in the gut is approximately twice the hepatic extraction and that
      cyclosporine absorption does not present a problem, with an average of 86% of the
      drug absorbed intact from its commercially available product in healthy
      volunteers. The boundary condition analysis described should have broad
      application in the differentiation of factors responsible for poor
      bioavailability.

PMID- 7586944
TI  - Buccal delivery of an alpha 2-adrenergic receptor antagonist, atipamezole, in
      humans.
AB  - OBJECTIVE: To evaluate the pharmacokinetics, systemic effects and clinical
      applicability of buccally administered atipamezole in healthy volunteers.
      METHODS: The study was carried out in two parts. In the first part, spray
      preparations of atipamezole hydrochloride in water/alcohol (50/50) solution were
      applied on buccal mucosa of six volunteers. Single doses of 5, 10, 20, and 40 mg
      atipamezole hydrochloride were administered in ascending order during separate
      sessions. In the second part, nine subjects received single 20 mg doses as buccal
      spray, intravenous infusion, or oral solution in randomized order. RESULTS:
      Values for area under the concentration-time curve for atipamezole (mean +/- SD)
      ranged from 26 +/- 4 ng x hr/ml after 5 mg to 112 +/- 21 ng x hr/ml after 40 mg
      and peak concentrations ranged from 11 +/- 3 ng/ml after 5 mg to 38 +/- 9 ng/ml
      after 40 mg. Individual peak concentrations were mainly measured at 30 and 60
      minutes after administration. Mean elimination half-lives were approximately 1
      1/2 hours after every treatment. In part two, a mean bioavailability of 33% was
      calculated for buccal administration (compared with intravenous), whereas
      systemic availability after an oral dose was < 2%. After intravenous
      administration the mean total clearance, apparent volume of distribution, and
      elimination half-life were 1.2 L/hr/kg, 2.9 L/kg, and 1.8 hours, respectively.
      The intravenous administration of 20 mg atipamezole hydrochloride produced a
      fivefold elevation in mean plasma norepinephrine concentration, a slight and
      short-lasting elevation in blood pressure and, in most subjects, increased
      tension, alertness and restlessness, and sweating. After buccal administration,
      some subjects reported short-lasting restlessness or tension after the 20 and 40
      mg doses. No significant changes in heart rate, blood pressure, or plasma
      catecholamines were observed. No effects were observed after swallowing of 20 mg
      atipamezole hydrochloride. The spray caused local reactions at buccal mucosa.
      Superficial white spots or areas were observed for several hours; these
      disappeared gradually. Subjects also reported transient numbness at the
      application site. CONCLUSION: Atipamezole hydrochloride is well absorbed
      systemically through oral mucosa. The oral bio-availability of atipamezole is
      negligible, probably because of extensive first-pass metabolism.

PMID- 7586949
TI  - Active transport of cimetidine into human milk.
AB  - Most xenobiotics are transferred from blood into breast milk by passive
      diffusion. However, an active transport mechanism has been speculated for
      cimetidine, and the purpose of this study was to characterize cimetidine transfer
      into human milk. Twelve healthy lactating volunteers received single oral doses
      of 100, 600, and 1200 mg cimetidine in a randomized, crossover design on 3
      different days. Blood and milk specimens were collected and assayed for
      cimetidine. In vitro measurements, including skim to whole milk concentration
      ratio, milk pH, and free fractions in serum and milk were used for a diffusion
      model prediction of milk to serum concentration ratio of cimetidine; the mean
      milk/serum ratio (+/- SD) was 1.05 +/- 0.18. The observed milk/serum ratio (5.77
      +/- 1.24) was 5.5 times higher than the milk/serum ratio predicted by diffusion.
      The observed milk/serum ratio for the three dosing regimens were not
      significantly different from one another. Time of peak concentration (tmax) in
      milk (3.3 +/- 0.7 hours) displayed a delay compared with serum tmax (1.7 +/- 0.6
      hours). Oral clearance for 1200 mg cimetidine dose (0.47 +/- 0.11 L/hr/kg) was
      significantly lower compared with oral clearance values for 100 and 600 mg
      cimetidine doses (0.59 +/- 0.11 and 0.57 +/- 0.13 L/hr/kg, respectively). The
      maternal dose of cimetidine ingested by a suckling infant based on body weight
      was estimated to be 6.7%, which appears to be safe under normal conditions. This
      study provides the first definitive evidence of an active transport system for
      drug transfer into human milk, which may have broader consequences for the
      suckling infant.

PMID- 7586945
TI  - Population characteristics of hepatic dihydropyrimidine dehydrogenase activity, a
      key metabolic enzyme in 5-fluorouracil chemotherapy.
AB  - Dihydropyrimidine dehydrogenase is the initial rate-limiting enzyme in catabolism
      of 5-fluorouracil, one of the most widely used cancer chemotherapeutic agents.
      Previous studies have shown the clinical importance of determination of
      dihydropyrimidine dehydrogenase in patients with cancer, particularly in those
      with deficiency of this enzyme who experience severe 5-fluorouracil-associated
      toxicity (including death) after 5-fluorouracil treatment. In the present study,
      dihydropyrimidine dehydrogenase activity was determined in 138 donor liver
      samples. A normal distribution of human liver dihydropyrimidine dehydrogenase
      activity was shown. The mean enzyme activity was compared across different groups
      by age, gender, and race, with no significant differences observed except that
      the mean enzyme activity in women was slightly higher than that observed in men.
      With use of a polyclonal antibody generated against human liver dihydropyrimidine
      dehydrogenase, Western blot analysis showed that dihydropyrimidine dehydrogenase
      protein in the liver cytosol correlated with the activity of this enzyme.

PMID- 7586946
TI  - Effects of felbamate on the pharmacokinetics of a low-dose combination oral
      contraceptive.
AB  - The effects of felbamate on the pharmacokinetics of a low-dose combination oral
      contraceptive containing 30 micrograms ethinyl estradiol and 75 micrograms
      gestodene were assessed in a randomized, double-blind, placebo-controlled
      parallel-group study in healthy premenopausal female volunteers established in a
      regimen of oral contraceptive use. They received either placebo or 2400 mg/day
      felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral
      contraceptive cycles (months 1 and 2). Pharmacokinetic assessments of ethinyl
      estradiol and gestodene were performed on day 14 of both cycles. To determine
      whether ovulation occurred, plasma progesterone and urinary luteinizing hormone
      levels were measured, and diaries recording vaginal bleeding were kept. Felbamate
      treatment resulted in a significant 42% decrease in gestodene area under the
      plasma concentration-time curve (0 to 24 hours) (p = 0.018) compared with
      baseline, whereas a minor but not clinically relevant effect was observed on the
      pharmacokinetic parameters of ethinyl estradiol. There were no changes in the
      pharmacokinetics of ethinyl estradiol or gestodene after placebo treatment. No
      volunteer showed hormonal evidence of ovulation; however, one volunteer reported
      the onset of intermenstrual bleeding during felbamate treatment. Because of the
      effect of felbamate on the pharmacokinetics of gestodene and the report of
      intermenstrual bleeding, it is possible that the contraceptive efficacy of low
      dose combination oral contraceptives may be adversely affected during felbamate
      treatment.

PMID- 7586948
TI  - S-mephenytoin hydroxylation phenotypes in a Jordanian population.
AB  - We tested the ability of 194 unrelated, healthy Jordanian volunteers to
      metabolize S-mephenytoin. Mephenytoin (100 mg) was coadministered with
      debrisoquin (10 mg) orally and urine was collected for 8 hours. Mephenytoin
      metabolism was tested according to three measures: the amount of 4
      hydroxymephenytoin, the S/R enantiomeric ratio, and the presence of a polar, acid
      labile metabolite in urine collected for 8 hours after the dose. The S/R ratio
      and the presence of the acid-labile metabolite were determined in the urine of 16
      patients who had low amounts of 4-hydroxymephenytoin (log hydroxylation index >
      or = 1). On examination of these three parameters of oxidation status, nine
      subjects were found to be poor metabolizers of mephenytoin by all three
      parameters. Thus 4.6% (95% confidence interval of 1.6% to 7.6%) of Jordanian
      subjects studied were poor metabolizers of mephenytoin. According to the Hardy
      Weinberg Law, the frequency of the recessive autosomal gene controlling the poor
      metabolizer status of mephenytoin was predicted to be 0.215% (95% confidence
      interval of 0.146% to 0.283%). These results are on the same order of magnitude
      as those determined in European white populations and constitute the first report
      in Arab populations.

PMID- 7586951
TI  - Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in
      healthy volunteers sedated with midazolam.
AB  - The purpose of this study was to model pharmacodynamically the reversal of
      midazolam sedation with flumazenil. Ten human volunteers underwent four different
      sessions. In session 1, individual midazolam pharmacokinetics and
      electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a
      computer-controlled infusion of midazolam with individual volunteer
      pharmacokinetic data was administered, targeting a plasma concentration
      corresponding to a light or deep level of sedation (20% or 80% of the maximal
      midazolam electroencephalographic effect) for a period of 210 minutes. After
      obtaining a stable electroencephalographic effect and constant midazolam plasma
      concentrations, a zero-order infusion of flumazenil was started until complete
      reversal of midazolam electroencephalographic effect was obtained. The flumazenil
      infusion was then stopped and the volunteer was allowed to resedate because of
      the constant midazolam drug effect. The electroencephalographic response was
      measured during a 180-minute period and analyzed by aperiodic analysis and fast
      Fourier transforms. In session 4, a midazolam plasma concentration corresponding
      to a deep level of sedation was targeted for 210 minutes to examine for the
      possible development of acute tolerance. No flumazenil was given in session 4.
      For a light sedation level, with a mean midazolam plasma concentration of 160 +/-
      64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil
      reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing
      50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean
      midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the
      equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site
      concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an
      estimate of the magnitude of the blood/central nervous system equilibration delay
      for flumazenil antagonism of midazolam sedation and further defines the
      usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic
      effect.

PMID- 7586950
TI  - Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo.
AB  - Dapsone toxicity is putatively initiated by formation of a hydroxylamine
      metabolite by cytochromes P450. In human liver microsomes, the kinetics of P450
      catalyzed N-oxidation of dapsone were biphasic, with the Michaelis-Menten
      constants of 0.14 +/- 0.05 and 0.004 +/- 0.003 mmol/L and the respective maximum
      velocities of 1.3 +/- 0.1 and 0.13 +/- 0.04 nmol/mg protein/min (mean +/- SEM).
      Troleandomycin (40 mumol/L) inhibited hydroxylamine formation at 100 mumol/L
      dapsone by 50%; diethyldithiocarbamate (150 mumol/L) and tolbutamide (400
      mumol/L) inhibited at 5 mumol/L dapsone by 50% and 20%, respectively, suggesting
      that the low-affinity isozyme is CYP3A4 and the high-affinity isozymes are 2E1
      and 2C. Disulfiram, 500 mg, 18 hours before a 100 mg oral dose of dapsone in
      healthy volunteers, diminished area under the hydroxylamine plasma concentration
      time curve by 65%, apparent formation clearance of the hydroxylamine by 71%, and
      clearance of dapsone by 26%. Disulfiram produced a 78% lower concentration of
      methemoglobin 8 hours after dapsone.

PMID- 7586952
TI  - Biphasic pressor responses to norepinephrine in humans.
AB  - We investigated pressor responses to intravenous bolus infusion of norepinephrine
      in seven healthy volunteers. Norepinephrine (1, 2, and 4 micrograms/kg) elevated
      blood pressure in a concentration-dependent manner and decreased heart rate. The
      pressor response to norepinephrine was biphasic (early and late). Intravenous
      administration of phentolamine (10 mg) completely abolished the pressor response
      to norepinephrine, and prazosin (5 mg, given orally) inhibited the early and late
      responses to a same extent. Continuous intravenous infusion of nicardipine (2
      micrograms/kg/min) inhibited the late pressor response but not the early one.
      These data suggest that bolus infusion of norepinephrine evoked the biphasic
      pressor response and that the late response depends on vasoconstriction by
      calcium influx through nicardipine-sensitive calcium channels.

PMID- 7586953
TI  - Changes in plasma warfarin levels and variations in steady-state prothrombin
      times.
AB  - OBJECTIVE: To determine the relative contribution of changes in the plasma
      warfarin level to variation in the serial steady-state prothrombin times.
      METHODS: This was a prospective observational cohort study performed at two
      outpatient anticoagulation clinics. Serial prothrombin times and paired plasma
      total warfarin levels were determined in a convenience sample of otherwise
      healthy patients who required long-term oral anticoagulation therapy with
      warfarin. RESULTS: Serial measurements were obtained from 129 patients, 60 of
      whom provided three or more serial samples. Analysis of covariance showed a
      highly significant (p = 0.0001) relationship between the anticoagulant effect and
      the logarithm of the warfarin concentration (R2 = 0.75), with 15.3% of the total
      variance attributable to the effect of warfarin and 31.1% attributable to
      individual variation in sensitivity to warfarin. In an analysis of the subjects
      who had three or more serial measurements, the mean weighted correlation
      coefficient for the relationship between the logarithm of the warfarin
      concentration and the anticoagulant response varied widely, from strongly
      negative to strongly positive, and as the range of observed prothrombin times
      increased, stronger positive correlation was observed. CONCLUSIONS: In this
      cohort, the plasma warfarin level was a strong predictor of observed changes in
      serial prothrombin time measurements. However, the correlation between clotting
      times and warfarin levels varied widely among subjects, particularly when the
      range of observed prothrombin times was moderate. This suggests that in these
      subjects, other factors, such as measurement error or pharmacodynamic changes,
      played a major role.

PMID- 7586954
TI  - Miscompliance by proxy.

PMID- 7586956
TI  - Buspirone miosis.

PMID- 7586955
TI  - Estimating bioavailability when clearance changes in time: the effect of model
      misspecification.

PMID- 7586957
TI  - MR imaging of the female pelvis.

PMID- 7586958
TI  - The role of pre-operative thallium-technetium subtraction scintigraphy in the
      surgical management of patients with solitary parathyroid adenoma.
AB  - Since 1985 we have practised scan directed unilateral cervical exploration for
      patients with primary hyperparathyroidism (HPT) on the basis of a solitary
      parathyroid adenoma, and who had a pre-operative thallium-technetium subtraction
      scintigram demonstrating one focus of activity (positive scan). Between 1985 and
      1993, a total of 160 patients with proven HPT and a technically satisfactory
      scintigram underwent neck exploration. Of these, 96 had positive preoperative
      scans, 81 (84.4%) of which accurately predicted the site of the tumour
      subsequently retrieved at operation. Seventy-four (77.6%) with positive scans,
      and 80 of the entire group, underwent unilateral cervical exploration with
      removal of a presumed single adenoma. Seventy-eight (97.5%) of these patients
      were cured of their HPT; two patients demonstrated mild persistent
      hypercalcaemia. Median operating time was significantly reduced for patients
      having unilateral as opposed to bilateral operation. Our results suggest that,
      when positive, thallium-technetium subtraction scintigraphy will accurately
      predict the site of a solitary parathyroid adenoma in a high proportion of
      patients and will thus permit a unilateral parathyroid exploration in these
      individuals. The usefulness of the technique is limited by its low sensitivity
      for small tumours.

PMID- 7586959
TI  - The use of ultrasound for monitoring breast tumour response to pro-adjuvant
      therapy.
AB  - In a prospective study, use of serial ultrasound (US) for monitoring tumour
      response to pro-adjuvant chemotherapy was assessed in 16 patients. Comparison was
      made with mammographic and pathological tumour size measurements. Clinical and
      radiological response to treatment was assessed using UICC (International Union
      Against Cancer) criteria. Comparison of clinical and US response to treatment
      showed some agreement in 60% and disagreement in 40%. This was comparable with
      clinical versus mammographic responses (55% and 45%). Correlation between
      calliper and pathological measurement was similar to that between US and
      pathological measurement (r = 0.51, P = 0.05; r = 0.50, P < 0.05). Mammography
      showed poorer correlation (NS). For assessment of final tumour size, US clinical
      measurements were comparable and better than mammography. US may be a useful tool
      in monitoring the response of breast tumours to pro-adjuvant therapy.

PMID- 7586960
TI  - The diagnostic value of colour Doppler ultrasound in central venous catheter
      related thrombosis.
AB  - AIM: This prospective study was performed to establish the correlation between
      colour Doppler ultrasound (US) observations and venography in detecting catheter
      related thrombosis. METHOD: Forty-four patients with subclavian venous catheters
      were studied. The sensitivity and specificity of colour Doppler US was determined
      for the diagnosis of central venous thrombosis and compared with contrast
      venography. Criteria considered to show the presence of catheter-related
      thrombosis included visualization of thrombus (T), absence of spontaneous flow
      (S), absence of phasicity of flow with respiration (P), incompressibility of the
      vein with probe pressure (C) and visualization of increased venous collaterals
      (V). RESULTS: Analysing each variable separately, P had the highest sensitivity
      (94%) and S had the highest specificity (100%). The best combinations for
      diagnosis were T+P, P+S, and T+P+S with a sensitivity of 94% and specificity of
      88%. Overall diagnostic value of colour Doppler US had a sensitivity of 94% and
      specificity of 96%. CONCLUSION: Colour Doppler US is a reliable method for
      detecting central venous catheter-related thrombosis, especially if several
      parameters are evaluated in combination.

PMID- 7586961
TI  - The use of ultrasound-guided cutting-needle biopsy in the neck.
AB  - Histological analysis of an abnormal neck mass has traditionally required an
      excision biopsy under general anaesthetic. We evaluated the safety and accuracy
      of a new spring loaded cutting-needle for obtaining tissues cores of neck masses
      under ultrasound (US) guidance. Sixty biopsies were performed on an outpatient
      basis under local anaesthesia in 52 patients referred with a neck mass. Patients
      ranged in age from 10 months to 89 years and masses varied in size from 5 mm to 5
      cm. Fifty-eight of the 60 biopsies provided a diagnostic histological specimen.
      Of the remaining two patients, one required open biopsy and the other returned
      for a second needle biopsy. All five cases of lymphoma were correctly diagnosed
      on needle biopsy; in three cases full tumour sub-classification was possible but
      in two patients an open biopsy was subsequently required. In 49 patients the
      needle biopsy obviated the need for a surgical biopsy for diagnostic purposes,
      although in 12 cases a therapeutic excision biopsy was performed. Apart from one
      subclinical haematoma, visualized on US, there were no immediate or delayed
      complications. In all patients, the histological diagnosis was compatible with
      subsequent clinical, radiological, surgical or autopsy findings. Cutting-needle
      biopsy of neck masses under US guidance is an effective and safe procedure which
      should be considered before resorting to routine surgery.

PMID- 7586962
TI  - Sonographic investigation of female infants with inguinal masses.
AB  - We present three cases of indirect inguinal hernias occurring in female infants
      aged between six weeks and two months. In each case ovarian tissue was identified
      sonographically within the herniated tissues. All cases presented with tender
      masses within the labia majora. This relatively common clinical condition should
      be high on the list of differential diagnoses of inguinal masses in female
      infants. Early recognition of an ovary decreases the risk of infarction plus the
      sonographic detection of ovarian tissue is diagnostic in gender differentiation
      of infants with ambiguous genitalia.

PMID- 7586965
TI  - Pelvic arterial embolization following hysterectomy and bilateral internal iliac
      artery ligation for intractable primary post partum haemorrhage.
AB  - A case of successful arterial embolization following hysterectomy and bilateral
      internal iliac artery ligation for intractable primary post partum haemorrhage is
      described. The selected artery was a branch of the inferior epigastric artery.
      Little has been written to date in the radiological literature about embolization
      via pelvic collateral vessels following arterial ligation. Although there is a
      good argument for postponing surgery until transcatheter embolization has been
      attempted, this case demonstrates that embolization can still be successful even
      when performed following surgery.

PMID- 7586963
TI  - Current usage of contrast agents, anticoagulant and antiplatelet drugs in
      angiography and angioplasty in the UK.
AB  - Currently, there is no consensus in the UK on what constitutes best angiographic
      practice. To provide a basis for discussion a questionnaire was sent to all
      Radiology and Cardiology departments in the UK. Information was requested on
      practice during diagnostic angiography and angioplasty regarding the type of
      contrast agent used, whether and how flush solution or contrast agents themselves
      were heparinised, and whether bolus doses of heparin were administered. The use
      of other supplementary drugs including corticosteroids was also explored. Two
      hundred of 353 (57%) of questionnaires were returned. Over 80% who replied used
      non-ionic contrast agents for all angiographic procedures. The majority of the
      smaller group, using ionic contrast agents for uncomplicated procedures, resorted
      to non-ionic contrast agents in a range of circumstances in both diagnostic
      angiography and angioplasty. Heparinized flush solutions were used by over 75%
      for both types of angiographic procedures, but employing a wide range of doses.
      Bolus doses of heparin were administered by over 80% performing angioplasty,
      again in a wide range of doses, with only (a few) cardiologists monitoring the
      anticoagulant effect by measuring the activated whole blood clotting time in the
      angiographic suite. Over 70% used aspirin or dipyridamole as supplementary
      agents, at the time of the angioplasty and, subsequently, continued these
      medications for a variable period. Corticosteroid prophylaxis for high risk
      patients, very variably defined, was felt necessary by 58%. A wide range of
      regimes of both dose and timing was noted.

PMID- 7586966
TI  - A barium enema training programme for radiographers: a pilot study.
AB  - We describe a training programme designed to instruct radiographers how to
      perform the double contrast barium enema (DCBE). The programme was assessed by
      comparing the first 50 unsupervised examinations with studies performed by senior
      registrars in radiology. Comparison was made by marking each study blind in terms
      of barium coating, colonic distension and visualisation of the colon in double
      contrast. A note was also made of the number of exposures, screening time,
      examination time and complications. No difference was found in any of these
      parameters when comparing the two groups. A further 50 patients were assessed at
      one year and this showed that standards had been maintained in terms of the above
      criteria. Follow-up at 3 years in the initial group has shown no missed
      pathology. We believe that delegation of the performance of the DCBE to
      radiographers is both acceptable to the patient and safe.

PMID- 7586967
TI  - Unusual perirenal sonographic pattern in malignant lymphoma of the kidney.

PMID- 7586964
TI  - Variation in angiographic practice and technique amongst interventional
      radiologists in the UK: assessment by postal questionnaire.
AB  - In order to ascertain the national variation in practice and workloads amongst
      interventional radiologists a questionnaire was sent to all members of the
      British Society of Interventional Radiologists of three or more years standing.
      The questionnaire was designed to assess changes in workload and angiographic
      practice amongst members at the various institutions. Results indicate that, over
      the last five years, there has been a dramatic increase in both diagnostic and
      therapeutic procedures performed, with an overall doubling of workload. There
      are, however, wide variations in angiographic practice and technique and referral
      pattern.

PMID- 7586968
TI  - Case report: ultrasound in the diagnosis of jejunal enterolith obstruction.

PMID- 7586969
TI  - Case report: recurrent pancreatitis caused by a duodenal duplication cyst
      communicating with the pancreatic duct.

PMID- 7586970
TI  - Case report: Fournier's gangrene--roentgenographic and sonographic findings.

PMID- 7586971
TI  - Case report: ossifying metastases from carcinoma of the large bowel demonstrated
      by bone scintigraphy.

PMID- 7586972
TI  - Case report: ruptured adrenal artery aneurysm.

PMID- 7586973
TI  - Update: abdominal tuberculosis--unusual findings on CT.

PMID- 7586974
TI  - Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25
      hydroxyvitamin D3 in patients with systemic lupus erythematosus.
AB  - 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte
      activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits
      proliferation, immunoglobulin production and the release of cytokines. Moreover,
      1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings
      suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological
      activation. Consequently, we found it of interest to study the serum levels of
      the two major metabolites of vitamin D3 in patients with systemic lupus
      erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and
      osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below
      those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25
      (OH)2 D3 corresponded to normal levels. There were no significant correlations
      between 25-OH D3 levels and clinical or paraclinical disease manifestations.
      Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3
      metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3
      and 25-OH D3 in patients with RA and OA corresponded to those of the controls.
      Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear,
      possible beneficial effects of administration of vitamin D to these patients
      should be considered.

PMID- 7586975
TI  - Anticardiolipin antibodies and antiphospholipid syndrome in chronic discoid lupus
      erythematosus.
AB  - Anticardiolipin antibodies (aCL) of immunoglobulin (Ig) G and M classes were
      determined in 28 patients affected with chronic discoid lupus erythematosus
      (CDLE), comparing their prevalence and levels to those in 60 healthy subjects
      matched for age and sex. A high and significant frequency of IgG (67.8%) and IgM
      (50.0%) aCL together with prevalence of high antibody levels was found in CDLE
      patients, while healthy controls had IgG and IgM aCL in 1.6% and 3.3% of cases
      respectively. Clinical features in keeping with the diagnosis of antiphospholipid
      syndrome were found in one patient (3.5%), which, as the first manifestation of
      the syndrome, showed a pulmonary thromboembolism which appeared some days after
      prolonged exposure to the sun. These results provide additional data on
      autoimmune phenomena in CDLE and suggest that aCL test should be considered as
      useful aids in immunological diagnosis of CDLE.

PMID- 7586976
TI  - Reduced bone mass and normal calcium metabolism in systemic sclerosis with and
      without calcinosis.
AB  - Forty-three female patients with systemic sclerosis divided into subgroups based
      on the extent of skin involvement and the presence of calcinosis, and 50 sex and
      age-matched healthy controls were investigated for bone mineral density (BMD) on
      the basis of radial (dual photon absorptiometry, Osteograph, NIM), lumbar, and
      total body measurements (dual energy X-ray absorptiometry, Lunar DPX, Lunar
      Corp.), and for parameters of calcium metabolism. The patients showed a lower BMD
      (mean +/- SD; mg/cm2) than the controls at the radial (313 +/- 69 vs 347 +/- 73;
      p < 0.005), lumbar (974 +/- 143 vs 1081 +/- 154; p < 0.005), and total body (997
      +/- 82 vs 1075 +/- 109; p < 0.05) determinations. The patients with the diffuse
      form of skin involvement had lower values than those with the limited form. There
      was a negative correlation between BMD and the duration of the disease. The
      presence of calcinosis was not found to have any effect on BMD. Calcium
      metabolism was found to be normal in each subgroup. It may be concluded that
      generalized osteoporosis is a feature of systemic sclerosis, with and without
      calcinosis. The extent and duration of the disease may play a role in determining
      bone loss.

PMID- 7586978
TI  - Changes in calcium and bone metabolism during treatment with low dose prednisone
      in young, healthy, male volunteers.
AB  - The effect of low dose prednisone on calcium and bone metabolism was evaluated in
      8 healthy, young, male volunteers. Sodium and calcium intake were kept stable
      during the whole study period of 7 weeks. Week 0 was the baseline period; during
      week 1, 3 and 5 prednisone (10 mg/day) was given, during week 3 together with 500
      mg elementary calcium and during week 5 with 4000 IU vitamin D on alternate days.
      During week 2, 4 and 6 no medication was given. No changes occurred in fasting
      urinary excretion of calcium or hydroxyproline, nor in serum levels of alkaline
      phosphatase, 25-Vitamin D, PTH, creatinine and inorganic phosphorus. A rapid
      decrease of serum osteocalcin during prednisone intake was found (p<0.01). This
      dip also occurred during prednisone and vitamin D treatment, but did not occur
      when calcium was added to prednisone, although the baseline value was lower at
      the start of combined treatment with prednisone and calcium. Serum calcium
      decreased during prednisone (p<0.05), but when prednisone was given together with
      calcium, an increase of serum calcium was found (p< 0.05). It is concluded that
      10 mg prednisone/day decreases bone formation, as shown by its effect on
      osteocalcin, while no influence is seen on bone resorption. Thus, prednisone,
      even when used in low doses, influences bone metabolism by uncoupling bone
      formation (decreased) and bone resorption (unchanged). These data suggest that
      the Cs-associated decrease in serum osteocalcin and in serum calcium does not
      occur during calcium suppletion.

PMID- 7586979
TI  - Complement-activating properties of IgM rheumatoid factors reacting with IgG
      subclasses.
AB  - To estimate the complement-activating property (CAP) of IgM rheumatoid factor
      (RF), which was purified from synovial fluids of patients with rheumatoid
      arthritis, in a reaction with each IgG subclass, the activation and binding of C4
      in the classical pathway of complement by IgM RF was measured in an enzyme-linked
      immunosorbent assay using biotinylated F(ab')2 antibody to human C4. The CAP of
      IgM RF reacting with IgG3 was significantly higher than that of IgM RFs bound to
      the other IgG subclasses (P < 0.01). These results suggest that IgM RF reacting
      with IgG3 in synovial fluid could induce a greater degree of complement-dependent
      inflammation in RA synovium than IgM RF reacting with other IgG subclasses.

PMID- 7586980
TI  - Osteoporosis in rheumatoid arthritis: effect of disease activity.
AB  - In addition to juxtaarticular osteoporosis, which appears to reflect
      predominantly local disease mechanisms, more generalized bone loss can occur in
      rheumatoid arthritis (RA). The aim of this study was to compare bone mineral
      density (BMD) of the lumbar spine and proximal femur in RA patients versus
      controls and evaluate the influence of disease related determinants. Twenty-seven
      patients with RA and twenty healthy subjects were included in this study. BMD was
      significantly reduced in RA patients compared with the control group. BMD was
      correlated with duration of disease, health assessment questionnaire scores, hand
      grip strength and erythrocyte sedimentation rate. These results support the
      hypothesis that BMD may be affected by RA related determinants.

PMID- 7586977
TI  - Fifteen months' follow-up of intensive inpatient physiotherapy and exercise in
      ankylosing spondylitis.
AB  - Long-term effects of three or four-week inpatient physiotherapy and exercise
      courses were studied in 141 adult patients with ankylosing spondylitis (AS).
      Eight cervical and thoracolumbar range of motion (ROM) measurements and straight
      leg raise test, vital capacity (VC) and fitness index were measured at the
      beginning and end of an intensive course and 15 months later. All nine mobility
      measurements, vital capacity and fitness index were significantly improved after
      the course. Fifteen months later only chest expansion and vital capacity had
      significantly deteriorated from the baseline, while CR, FFD and fitness index
      were still significantly better. Disease duration did not influence treatment
      results. We conclude that it is possible by means of intensive rehabilitation
      courses to prevent for more than one year deterioration of spinal function and
      fitness in AS patients irrespective of disease duration.

PMID- 7586983
TI  - Lymphatic obstruction in rheumatoid arthritis.
AB  - We describe four patients with rheumatoid arthritis and unilateral upper limb
      oedema. In all cases, qualitative lymphoscintigraphy showed lymphatic obstruction
      in the affected limb.

PMID- 7586981
TI  - Microheterogeneity of acute phase proteins in patients with clinically active and
      clinically nonactive osteoarthritis.
AB  - Microheterogeneity of two acute phase glycoproteins, alpha-1-acid glycoprotein
      (AGP) and alpha-1-antichymotrypsin (ACT), concentrations of AGP, ACT, and C
      reactive protein (CRP), and levels of three cytokines: interleukin 1 beta (IL-1
      beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were
      determined in 61 serum samples and 7 synovial fluids (SFs) obtained from patients
      (n = 61) with osteoarthritis. Using affinity immunoelectrophoresis with
      concanavalin A (conA), a significant decrease in the reactivity of AGP and ACT
      with this lectin was found in patients with clinically active osteoarthritis when
      compared to those with clinically nonactive disease (p < 0.001 and p < 0.05,
      respectively). There was no increase in the concentration of AGP, ACT, and C
      reactive protein (CRP) in the sera examined. In particular, no increase in the
      serum level of these proteins was found in the patients with clinically active
      disease. Low concentrations of IL-6 and TNF-alpha were found in most sera and SFs
      examined. In 6 out of 7 SFs available, IL-6 concentrations were higher than in
      the respective serum samples but for TNF-alpha the same could be shown in one
      case only. Low concentrations of IL-1-beta were found in 4 serum samples obtained
      from patients with clinically active osteoarthritis and in no SF specimen
      studied. In the entire group, serum level of TNF-alpha correlated weakly with the
      AGP and ACT reactivity coefficients with conA (r = 0.3634, p < 0.005 and r =
      0.3324, p < 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586982
TI  - Evaluation of arthritis in Reiter's disease by bone scintigraphy and radiography.
AB  - Tc-99m MDP bone scans were used to evaluate the articular inflammation in 38
      patients with Reiter's disease and compared with clinical examination and
      radiologic findings. Our data showed that Reiter's disease predominantly involves
      the lower limbs, especially the heels, which may be a characteristic feature of
      Reiter's disease. Bone scans revealed a high diagnostic sensitivity in the
      detection of clinical arthritis in all peripheral joints, especially in the small
      joints of the four limbs. The diagnostic sensitivity of radiography was generally
      lower than bone scintigraphy. In the presence of positive radionuclide findings,
      clinical arthritis was found in most joints. The scintigram, however, detects a
      greater number of abnormalities than does clinical assessment in the
      sternoclavicular joints, shoulders, metacarpophalangeal joints, and tarsals.
      Because of its high sensitivity, bone scintigraphy is capable of detecting
      subclinical arthritis, and might provide more objective evidence of early
      inflammatory joint disease and additional information regarding the pattern of
      joint involvement. In view of the advantages of low patient radiation exposure,
      high sensitivity, and the ability to survey the whole body, we consider bone
      scintigraphy as useful and better than radiography in the detection of early
      articular inflammation and in establishing the extent and pattern of arthritis in
      Reiter's disease.

PMID- 7586984
TI  - Antibodies to human immunodeficiency virus (HIV-1) in autoimmune diseases:
      primary Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis
      and autoimmune thyroid diseases.
AB  - The aetiology of autoimmune diseases remains unknown. The relationship between
      virus, and more recently retrovirus, has been suggested with this group of
      diseases. Immunoblotting is a useful method for determining the presence of
      proteins coded by different retrovirus genes. Since the prevalence of these types
      of proteins in patients with primary Sjogren's syndrome (SS), systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA) and autoimmune thyroid diseases
      has not been fully established, the aim of this work was to determine the
      prevalence of antibodies to immunodeficiency human virus type 1 (HIV-1) proteins
      in these diseases and their possible relationship with the presence of anti
      nuclear, anti-DNA, anti-SSA (Ro) and anti-SSB (La) autoantibodies. Antibodies to
      human immunodeficiency virus (HIV-1) were studied in a group of 341 patients with
      autoimmune diseases (77 SS, 98 SLE, 75 RA, 91 autoimmune thyroid diseases) and
      126 blood donors as a control group. A Western blot was used to detect antibodies
      to HIV-1, and a double polymerase chain reaction (PCR) using nested primers in
      the gag and pol gene of HIV-1. Antinuclear antibodies, anti-DNA, anti-SSA (Ro)
      and anti-SSB (La) were determined by enzyme-linked immunosorbent assays. At least
      one band was shown on immunoblotting in 26% of patients with autoimmune diseases
      and 35% of controls. The presence of antibodies to p55 or p68 proteins in
      patients with SS or SLE proved to be the only statistically significant
      difference between the other autoimmune diseases studied and the control group.
      These antibodies were not associated with autoantibodies ANA, DNA, SSA (Ro) or
      SSB (La).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7586988
TI  - Benign osteopetrosis, in a patient with sickle-cell beta+ (beta+) thalassaemia.
AB  - We describe a case of a patient suffering from benign osteopetrosis and sickle
      cell beta+ thalassaemia. This case allows us to study the combined action of
      various pathogenetic mechanism involved in both diseases. The coexistence of
      osteopetrosis with sickle-cell beta+ thalassaemia seems to intensify the anaemia
      and sickling, but does not appear to modify the course of the osteopetrosis.

PMID- 7586985
TI  - Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: effect of
      methotrexate, sulphasalazine and hydroxychloroquine therapy.
AB  - The aim of this study was to assess the correlations of the serum soluble
      interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters
      and response to treatment with second line drugs in patients with rheumatoid
      arthritis (RA). Sixty-seven patients with active disease completed a 24-week,
      open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or
      hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and
      after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients
      than in controls (P = 0.0001) and correlated significantly only with erythrocyte
      sedimentation rate (P = 0.03) and with Chronic Arthritis Systemic Index (P =
      0.01) at study entry. No correlation was found between serum sIL-2R and other
      laboratory and clinical indices of disease activity. After 24 weeks of treatment
      no differences in serum sIL-2R in comparison with basal levels were found in
      either responding or in non-responding patients, although the mean reduction of
      sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated
      groups. These data suggest that in RA the measurement of sIL-2R should be used
      with caution as an isolated index of disease activity and that it is not a useful
      marker of response to treatment with second line drugs.

PMID- 7586986
TI  - Spinal stenosis due to posterior syndesmophytes in a patient with seronegative
      spondyloarthropathy.
AB  - Spinal involvement in spondyloarthropathy is characterized by inflammation
      concentrated at the site of bony insertion of ligaments and bones. These
      inflammatory sites show a peculiar tendency towards prominent fibrosis,
      ossification and new bone formation (syndesmophytes). The syndesmophytes arise
      either at the margins of intervertebral disc and these are called marginal
      syndesmophytes as in ankylosing spondylitis, or from the vertebral bodies beyond
      their corners and are called nonmarginal syndesmophytes as in psoriatic arthritis
      and Reiter's syndrome (1,2). In some references and in the European literature,
      the term 'syndesmophyte' is usually reserved for the vertical ossification that
      bridges two adjacent vertebrae in ankylosing spondylitis (3). Syndesmophytes
      predominate on the anterior and lateral aspect of the spine (1-3). We report a
      patient with undifferentiated spondyloarthropathy with posterior syndesmophytes
      resulting in symptomatic spinal stenosis.

PMID- 7586987
TI  - Pitfall of stiff shoulder: inveterated posterior dislocation.
AB  - The authors relate the observation of an inveterated bilateral posterior
      dislocation, occurring during a generalized epileptic attack and mimicking a
      painful stiff shoulder. The clinical signs (i.e. aetiologic circumstances causing
      a forced internal rotation, limitation or absence of external rotation) and
      radiological data, especially the necessity of a profile X-ray, which lead to the
      diagnostic are reiterated. The interest of computerized tomography in the pre
      operative assessment is underscored.

PMID- 7586989
TI  - Ochronotic arthropathy: rapid destructive hip osteoarthritis associated with
      metabolic disease.
AB  - Ochronosis is a musculoskeletal manifestation of alkaptonuria, an inherited
      metabolic disorder associated with various systemic abnormalities related to the
      deposition of homogentisic acid pigment in connective tissues. This report
      describes a 58-year-old woman with ochronotic arthropathy who, in addition to the
      typical clinical features of the disorder, presented with rapidly progressive hip
      osteoarthritis. The destruction of the joint architecture and the severe
      functional impairment necessitated a total hip replacement which resulted in a
      satisfactory outcome.

PMID- 7586990
TI  - Spontaneous fracture of the sternum simulating myocardial infarction.
AB  - Spontaneous fractures of the sternum are rare but worth knowing as they may
      simulate acute cardiac and pulmonary emergencies. A case of an insufficiency
      sternal fracture mimicking myocardial infarction and subsequent anginal pain is
      presented. The risk factors of this condition, its clinical features and the
      diagnostic procedures are discussed. Spontaneous fractures of the sternum should
      be considered as a diagnostic possibility for unexplained chest pains in the
      elderly.

PMID- 7586991
TI  - Long-term follow-up of low-dose methotrexate therapy in one case of idiopathic
      retroperitoneal fibrosis.
AB  - Idiopathic retroperitoneal fibrosis (RPF) is characterized by the development of
      a fibrotic mass surrounding the abdominal aorta and its branches, of unknown
      aetiology. Several immunological mechanisms can be operative in the pathogenesis
      of RPF. Based on this assumption we treated a patient affected by idiopathic RPF
      with low-dose methotrexate (MTX) therapy. To our knowledge this is the first
      example of the effectiveness and safety of a long-term low-dose MTX treatment in
      the post-surgical management of RPF.

PMID- 7586992
TI  - Successful treatment with corticosteroid in a patient with progressive diaphyseal
      dysplasia.

PMID- 7586993
TI  - Superior sagittal sinus thrombosis in a patient with Behcet's disease and the
      Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 7586994
TI  - Henoch-Schonlein purpura associated with coxsackie-virus B1 infection.

PMID- 7586995
TI  - [Update on the use of interferons in clinical practice].
AB  - Discovered by Isaac and Lindemann as a substance able to induce a biological
      interference among viruses and host cells, interferon appeared to include three
      main antigenic classes: alpha, beta and gamma. There is a large variety of
      actions exhibited by different types of interferon and among them it is possible
      to distinguish an antiviral, antineoplastic, immunomodulatory or hormonal
      activity. Many years ago, the antiviral action seemed to be relative to some
      cellular membrane disorders, but later other mechanisms were stressed. Among
      them, it is worth describing the transcription and transduction of antiviral
      proteins like the oligoadenilsinthetase and proteinphosphokinase, able to cause
      the viral RNA breackage. The antineoplastic action is exerted by direct and
      indirect mechanisms. Direct mechanisms include an antiproliferative activity and
      the induction to cellular differentiation whereas the indirect ones involve the
      enhancement on tumor cell surfaces of some tumor associated antigens included in
      the I class of MHC system. The immunomodulatory action is exerted by the
      stimulation of macrophages, T cells and Killer cells cytotoxic activity. The list
      of viral diseases sensitive to interferon treatment includes condiloma acuminata,
      herpes zoster, chronic B and C hepatitis and Kaposi sarcoma AIDS-related. High
      proportions of overall response rate were observed among interferon treated
      patients with condiloma acuminata (80-100%). The use of interferon in the
      treatment of herpes zoster achieved good results regarding a shorter duration of
      the time spent to induce the chest pains and cutaneous symptoms disappearance
      when compared with that relative to other antiviral drugs. Results obtained in
      the treatment of chronic B and C hepatitis regard the disappearance of viral
      replication serological markers and the improvement of histological and enzymatic
      pattern. The effectiveness of interferon in the therapy of Kaposi sarcoma is
      demonstrated by the reduction of cutaneous symptoms and recurrent infectious
      diseases incidence. The use of interferon in treatment of solid tumors seems to
      play secondary role and, at any rate, to be adjuvant to chemotherapy. The
      administration of beta interferon as therapy of breast cancer seems to increase
      the estrogens and progesterone concentration in the neoplastic tissue and so it
      aims to improve the sensitivity to the tamoxifen treatment. The addition of
      interferon alpha both to 5-FU and cis-platinum seems to improve the proportion of
      overall response rate respectively in the treatment of colon cancer and head and
      neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7586996
TI  - [Multiple sclerosis and major depression resistant to treatment. Case of a
      patient with antidepressive therapy-induced mood disorder, associated with manic
      features].
AB  - Patients with multiple sclerosis show higher prevalence of psychiatric disorders
      compared to general population, that are hardly managed by pharmacotherapy. In
      the present report a female patient, 44 years old, with diagnosis (according to
      DSM-IV) of 340 multiple sclerosis, 296.32 major depressive disorder, recurrent,
      moderate, 292.84 antidepressant-induced mood disorder, with manic features, is
      described. In this patient depressive symptoms did not respond to a number of
      drugs, including tricyclic antidepressants, selective serotonine re-uptake
      inhibitors hand lithium. Moreover, she had hypomanic and manic episodes induced
      by two different antidepressant, hydroxy-tryptophan and clorimipramine. Until
      today, only amisulpride (50 mg/die for four months, then 50 mg every two days for
      two months) has shown a significant effect on depressive symptomatology,
      moreover, this drug has not induced the occurrence of manic symptoms.

PMID- 7587000
TI  - Microalbuminuria in non-insulin dependent diabetes mellitus.

PMID- 7586998
TI  - [Evaluation of the treatment with thymopentin associated with radiotherapy in
      head and neck tumors].
AB  - The aims of the study has been the analysis of the optimal conditions for the use
      of thymopentin in reducing the incidence and severity of early and late
      complications following radiotherapy of patients with head and neck cancers
      submitted to radiotherapy by means of cobalt or linear accelerator. 168 patients
      of 10 Center have been examined. Analysis of the results demonstrated that the
      tymopentin reduce the incidence and severe reactions (p < 0.05) in statistically
      significant manner in cases of irradiation of the hypopharynx, oropharynx in oral
      cavity. The complications were more frequent during cobalt beam therapy (p <
      0.01) and the beneficial effect of the immunomodulating treatment were greater
      for females than the males (p < 0.05).

PMID- 7586997
TI  - [Evaluation of the effectiveness and tolerability of MED 15 vs. piroxicam in
      patients with acute epicondylitis].
AB  - In this trial we studied 30 patients with acute epicondylitis: 15 were treated
      with Med 15, a new non-steroidal anti-inflammatory drug, and 15 with piroxicam.
      Med 15 was administered orally for 15 days: the first 2 days 2 tablets daily
      (1.200 mg) and the following 13 days 1 tablet daily (600 mg). Piroxicam was
      administered 2 tablets the first 2 days and 1 tablet daily the following 13 days.
      It was demonstrated that the new compound is significantly more active and better
      tolerated than the reference drug.

PMID- 7586999
TI  - [Effect of sumatriptan on facial temperature variations, blood pressure and
      electrocardiogram in healthy subjects and patients with migraine without aura].
AB  - 40 patients were evaluated for skin temperature changes from baseline
      measurements and after 6 mg subcutaneous sumatriptan administration. During
      examination, skin temperature were recorded on a color picture at 10', 20', 30',
      60', 90' and 120 minutes after sumatriptan administration. At the some time,
      heart rate (HR), systolic (SBP), diastolic (BDP) blood pressure and ECG
      monitoring were automatically recorded. The patients were subgrouped as follow:
      20 non migrainous control subjects (6 males and 14 females) aged 19 to 55 years
      (mean age 39.5 +/- 15.4); 20 headache free migrainous patients (6 males and 14
      females) aged 25 to 46 years (mean age 37.8 +/- 8.4). Our data demonstrate a
      significant reduction in skin temperature (face) in all patients studied. 10
      minutes after sumatriptan administration a significant increase (p > 0.001) both
      in SBP and BDP was observed. This findings suggest that sumatriptan show a
      vasoconstrictor effect as demonstrate by reduction in face temperature both in
      nonmigrainous and in migrainous patients. The unchange in HR and ECG and the
      transient increase in blood pressure, not associated with clinical symptoms,
      suggest that this drug may be used in migrainous patients.

PMID- 7587002
TI  - Screening for microalbuminuria in type 2 diabetic patients: the evaluation of a
      dipstick test in general practice.
AB  - To evaluate the Micral test, a semiquantitative dipstick test, in a general
      practice setting, 317 Type 2 diabetic patients completed a screening for
      microalbuminuria by means of the Micral test as well as immuno-nephelometry with
      the Disc 120 immuno-nephelometer (Hyland, Nivelles, Belgium). Data were collected
      in 10 general practices performing the Nijmegen Monitoring Project. At a regular
      check-up each Type 2 diabetic patient was asked to collect first morning urine
      samples on three consecutive days. The sensitivity of the Micral test was 67%,
      the specificity 93%. Between the practices the sensitivity ranged from 58% to
      81%, the specificity from 87% to 95%. Microalbuminuria, defined as a mean urine
      albumin concentration > or = 20 mg I-1 by nephelometry on three consecutive days,
      was found in 66 patients (21%). The first Micral test correctly picked out these
      patients with microalbuminuria in 70% of the cases and in 90% those patients
      without microalbuminuria. The diagnostic performance of the Micral test was
      further proved by a Receiver Operating Characteristic (ROC) curve. The Area Under
      the Curve (AUC) of the Micral test was 0.84 (95% CI 0.78-0.90). Micral test
      results of 0 and 10 should be regarded as negative.

PMID- 7587003
TI  - Insulin increases renal magnesium excretion: a possible cause of magnesium
      depletion in hyperinsulinaemic states.
AB  - The effects of insulin upon renal magnesium excretion were examined. Urinary
      magnesium excretion rates were measured in seven healthy volunteers (three men,
      four women) before and during a euglycaemic, hyperinsulinaemic clamp. Insulin was
      infused at 120 pmol m-2 min-1 and at 240 pmol m-2 min-1. Compared to baseline,
      the renal magnesium excretion increased 30% during the infusion of insulin at a
      rate of 120 pmol m-2 min-1. During infusion of insulin, 240 pmol m-2 min-1, renal
      magnesium excretion increased 50% compared to baseline. There were no changes in
      either glomerular filtration rates, plasma magnesium, urinary volume or general
      changes in the renal handling of divalent ions as judged by an unchanged urinary
      excretion rate of calcium (0% during infusion of insulin, 120 pmol m-2 min-1, and
      8% increase during infusion of 240 pmol m-2 min-1 (NS). During the 120 pmol m-2
      min-1 insulin infusion rate, plasma insulin rose from 46.1 pmol I-1 to 158.8 pmol
      I-1 and during the 240 pmol m-2 min-1 insulin infusion rate, mean plasma insulin
      concentration was 361.4 pmol I-1. Thus, physiological concentrations of insulin
      induce a specific increase in the renal excretion of magnesium. This might partly
      explain the magnesium depletion observed in various hyperinsulinaemic states,
      diabetes mellitus, atherosclerosis, hypertension, and obesity.

PMID- 7587004
TI  - Decreased sialidase activity in mononuclear leucocytes of type 1 diabetic
      subjects: relationship to diabetic complications and glycaemic control.
AB  - Leucocyte surface sialic acid content influences surface charge, deformability,
      and leucocyte-endothelial interaction. Abnormal leucocyte structure and function
      contributes both to microvascular damage and diabetic complications. The aim of
      this study was to investigate altered leucocyte SA metabolism in diabetic
      subjects and measure lysosomal sialidase which regulates leucocyte surface
      sialylation. We examined 26 Type 1 (insulin-dependent) diabetic subjects with
      retinopathy, 26 Type 1 diabetic subjects without complications, and 38 matched
      normal control subjects. Sialidase was assayed in freshly prepared sonicates of
      pure mononuclear leucocytes (MNLs), using the fluorometric substrate 4-methyl
      umbelliferyl-N-acetylneuraminic acid. In the subjects with diabetes there was a
      significant negative correlation between MNL sialidase activity and both HbA1c
      (rs = 0.37, p = 0.007) and fructosamine (rs = -0.31, p = 0.026). MNL sialidase
      activity was significantly decreased in diabetic subjects with clinical evidence
      of complications compared to control subjects. HbA1c was significantly higher (p
      = 0.036) in diabetic patients with complications compared to those without. The
      observed decrease in MNL sialidase activity related to diabetic control may be
      important in the pathogenesis of vascular damage. Diabetes-associated changes in
      sialylation of functional cell surface glycoconjugates may have important
      clinical consequences.

PMID- 7587001
TI  - Microalbuminuria: prognostic and therapeutic implications in diabetic and
      hypertensive pregnancy.
AB  - Microalbuminuria is defined as urinary excretion of albumin that is persistently
      above normal, although below the sensitivity of conventional semiquantative test
      strips. Several studies have reported that Type 1 diabetic patients with
      microalbuminuria are apparently more likely to develop diabetic nephropathy
      eventually progressing to renal failure. Microalbuminuria is also a strong
      predictor of mortality in Type 2 diabetes, and is correlated with increased blood
      pressure in patients with benign essential hypertension. Radioimmunoassay
      revealed a significantly higher urinary albumin excretion rate in normal pregnant
      women in the third trimester of pregnancy, compared to the second and first, and
      compared to non-pregnant women. Microalbuminuria was found in 30% of women who
      had a record of gestational diabetes mellitus. Published results are
      controversial regarding the assumption that microalbuminuria is an early
      predictor of pregnancy-induced hypertensive complications.

PMID- 7587005
TI  - No important differences in glycaemic responses to common fruits in type 2
      diabetic patients.
AB  - The aim of this study was to determine the glycaemic indices (GIs), peak
      incremental indices (PI), and time of peak increment (TPI) of eight kinds of
      fruits and their relationship with the type and amount of simple sugars directly
      assayed in the fruits. Sixty-one type 2 diabetic patients randomized into eight
      groups--one for each category of fruit--participated in the study. GIs consisted
      of the following: pears = 60 +/- 4.9; apples = 63 +/- 8.3; oranges = 68 +/- 6.5;
      grapes = 70 +/- 7.5; plums = 75 +/- 8.4; peaches = 80 +/- 7.4; apricots = 82 +/-
      9.1; bananas = 83 +/- 8.5. The PI values (mmol I-1) were the following: grapes =
      2.52 +/- 0.26; apples = 3.13 +/- 0.75; pears = 3.48 +/- 0.55; oranges = 4.02 +/-
      0.42; peaches = 4.07 +/- 0.38; apricots = 4.08 +/- 0.47; plums = 4.2 +/- 0.45;
      bananas = 4.45 +/- 0.39. There was no statistical differences in GI, and PI,
      within the different fruits. TPI of grapes (43.3 +/- 5.2 min), oranges (45 +/-
      5.6 min), and peaches (45 +/- 5.6 min) were statistical different (p < 0.01) in
      respect to apricots (81.4 +/- 5.5 min). GIs were positively correlated with total
      glucose contained in the fruits (p < 0.05) and with PI (p < 0.0002); negatively
      with fructose both free (p < 0.02) and total (sum of free and present in sucrose
      (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587006
TI  - Neuropsychological function in older subjects with non-insulin-dependent diabetes
      mellitus.
AB  - Neuropsychological function was compared in three well-matched groups of
      subjects: Group 1, 20 diabetic patients with hypertension, mean age 69.1 +/- 4.8
      years, 14 males and 6 females; Group 2, 20 normotensive diabetic patients, mean
      age 69.0 +/- 6.2 years, 14 males and 6 females; Group 3, 20 healthy community
      controls, mean age 68.1 +/- 4.5 years, 13 males and 7 females. There were no
      significant differences between the groups in education or estimated IQ using the
      NART (National Adult Reading Test). Groups 1 and 2 did not differ significantly
      in duration of diabetes (mean 10.6 and 9.5 years, respectively), or mean
      glycosylated haemoglobin, HbA1 (mean 9.8 and 10.6%, respectively), or mean blood
      glucose before and after testing. On a battery neuropsychological tests,
      sensitive to cognitive impairment in older subjects, analysis of covariance using
      estimated IQ as the covariate showed no significant differences between the
      groups on tests of recall, with (Brown-Peterson Test) and without (Kendrick
      Object Learning Test) interference, forward and backward digit span,
      concentration (serial subtraction), verbal fluency, immediate and delayed prose
      recall, digit symbol substitution or psychomotor speed (Kendrick Digit Copying
      Test). These results provide no support for an association between cognitive
      deficits and Type 2 diabetes mellitus in older subjects or for the view that such
      deficits may also be mediated by hypertension.

PMID- 7587007
TI  - Relation of fetal growth to adult muscle mass and glucose tolerance.
AB  - Recent studies show reduced fetal growth is associated with insulin resistance
      and a raised prevalence of glucose intolerance in adult life. Because early
      growth retardation in animal models leads to permanent changes in body
      composition and a reduction in the mass of muscle, a major insulin sensitive
      tissue, reduced adult muscle mass could explain the link between impaired fetal
      growth and glucose intolerance. To investigate this hypothesis, muscle mass has
      been determined in a group of men and women aged around 50 who were born in
      Preston, Lancashire and compared with their birthweight or body size at birth and
      their current insulin resistance and glucose tolerance. Subjects who had lower
      birthweights were shorter and lighter but their weight adjusted for height (BMI)
      was similar to that of other subjects. Much of the difference in weight was
      accounted for by a reduction in muscle mass. Muscle mass as estimated by the
      urinary creatinine excretion rose from 18.8% of body weight in women who had
      birthweights of 2.5 kg or less to 24.7% of bodyweight in those with birthweights
      of 3.4 kg or more. Trends in men were similar. Regression analysis showed that
      adult muscle mass was predicted by low birthweight (p = 0.004), low placental
      weight (p = 0.02), and small head circumference (p = 0.02) but not, however, by
      thinness at birth, the birth measurement most predictive of insulin resistance.
      In addition there were no significant relationships between muscle mass and
      insulin resistance or glucose tolerance in either men or women.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7587008
TI  - Comprehensive diabetes care in North Tyneside.
AB  - The care of a 25% (n = 559) random sample of all patients with diabetes in a
      district was assessed to determine whether comprehensive diabetes care was being
      achieved. Process measures initially assessed were repeated 3 years later after
      several changes in the programme of diabetes care were instituted. The number of
      patients with diabetes in structured care increased from 91% to 95% between 1991
      and 1994, at the same time as an increase in prevalence from 1.2% to 1.8%. There
      was a shift in the proportion of patients attending primary care from 27% to 40%.
      There were significant improvements in the delivery of process measures including
      education. The majority of process measures were delivered to more than 75% of
      the district diabetes population (for example HbA1c in 93%, fundoscopy in 86%,
      urine protein in 81%, education on diabetic control in 84%). Comprehensive
      diabetes care has not yet been fully achieved in North Tyneside district but the
      programme of care has shown continuous improvement over a 3-year period.
      Comprehensive diabetes care should be an aim of every district diabetes
      programme.

PMID- 7587009
TI  - Variation of diabetes mellitus prevalence in general practice and its relation to
      deprivation.
AB  - This is an observational study to compare age standardized diabetes prevalences
      and relate these to socio-economic measures of deprivation. It includes data from
      eight general (family) practices in the Bristol, UK, area with no ethnic
      minorities affecting diabetes prevalence. A total population of 71 599 was
      covered, including 181 Type 1 and 901 Type 2 diabetic patients, 91 of whom were
      controlled with insulin, 499 with oral hypoglycaemics, and 311 with diet alone.
      Actual Type 1 and Type 2 diabetes prevalences were standardized to what they
      would be if each practice had the UK national age profile. Total standardized
      diabetes prevalence varied from 1.31% to 2.51% (p < 0.001) and Type 2 diabetes
      prevalence from 0.97% to 2.29% (p < 0.001). There was no significant variation in
      the prevalence of Type 1 diabetes. The Spearman rank correlation coefficient
      indicated a significant association between standardized diabetes prevalence and
      two measures, the Jarman and Townsend indices, of deprivation in the electoral
      ward where each practice was situated. Total standardized diabetes prevalence was
      significantly correlated with each of the Jarman and Townsend indices (r = 0.76,
      p < 0.05). Standardized Type 2 diabetes prevalence was similarly significantly
      correlated to each deprivation index (rs = 0.74, p < 0.05). Type 2 diabetes
      prevalence is affected by socio-economic factors with implications for health
      targets and capitation based budgets.

PMID- 7587010
TI  - Ethnic differences in the perception of a video developed for a multiethnic
      diabetes prevention programme in south Auckland, New Zealand.
AB  - Videos were developed to help increase diabetes awareness among local Maori,
      Pacific Islands and European communities. The Maori and Pacific Islands versions
      incorporated modifications to the basic content to make them more appropriate for
      the target audience. Lay audiences, comprising 108 Europeans, 94 Maori and 90
      Pacific Islands people in 12 different sites, viewed the version of the video
      tailored to their ethnic group. The Maori version was also viewed by 32 Diabetes
      Nurse Specialists. Likert scale ratings and open-ended questions were used to
      evaluate the video. The video was rated highly by all audiences and most subjects
      were able to repeat the main messages of the video. Compared with Maori and
      Pacific Islands subjects, Europeans found the video the easiest to understand but
      gained the least information. Maori and Pacific Islands subjects would have
      preferred a longer video ( > 17 minutes). Different viewing sites revealed
      evidence of within-ethnic-group heterogeneity. Pacific Islands subjects
      particularly appreciated the educational components, while Maori and Europeans
      were more likely to comment on presentation. Audio-visual material is perceived
      differently by different ethnic groups, such differences need to be addressed
      when embarking on diabetes awareness campaigns.

PMID- 7587011
TI  - An evaluation of fructosamine estimation in screening for gestational diabetes
      mellitus.
AB  - Although persuasive arguments against routine screening for gestational diabetes
      mellitus (GDM) have been made, it is widely but not universally performed as a
      part of antenatal care. There is no international agreement on methods or
      criteria used for screening (or for diagnosis), and administered glucose-load
      methods have significant practical difficulties in a busy antenatal clinic
      setting. However, recent evidence supports the concept of an increased level of
      importance being given to a diagnosis of GDM, with interest in the fetal and
      neonatal origins of adult disease being added to the short-term obstetric and
      fetal concern during pregnancy. A second generation fructosamine test, corrected
      for total protein, has been evaluated as a practical alternative to glucose
      screening for GDM in a busy, multi-ethnic antenatal clinic. This achieved a 79.4%
      sensitivity and a 77.3% specificity for a diagnosis of GDM confirmed by a glucose
      tolerance test using Carpenter's modified criteria. In view of the organizational
      simplicity of this sample/test requirement, a wider evaluation is suggested
      together with a re-evaluation of clinical outcome criteria rather than blood
      glucose levels alone.

PMID- 7587013
TI  - The UK Diabetes Dataset: a standard for information exchange. Diabetes Audit
      Working Group of the Research Unit of the Royal College of Physicians. British
      Diabetic Association.

PMID- 7587015
TI  - A desktop guide for the management of non-insulin-dependent diabetes mellitus
      (NIDDM) by the European NIDDM Policy Group.

PMID- 7587012
TI  - Are frozen urine samples acceptable for estimating albumin excretion in research?
AB  - Timed urine collections from diabetic children and adolescents were assessed for
      urinary albumin excretion rate (microgram min-1) before and after freezing at -20
      degrees C. Freezing had the effect of changing the estimation such that frozen
      values could differ from that of the fresh, by as much as one half to twice as
      much. The variation depended on the concentration defining the initial albumin
      excretion rate but was not influenced by the length of storage when frozen. We
      conclude that researchers should be aware that freezing and storing of urine
      samples prior to albumin concentration assessments can affect the absolute values
      obtained. It would appear more appropriate to analyse samples prior to freezing
      to be certain of obtaining true prevalence estimates of microalbuminuria.

PMID- 7587016
TI  - The vitamin C connection.

PMID- 7587014
TI  - Aetiopathogenesis and management of impotence in diabetic males.

PMID- 7587017
TI  - A cognitive developmental approach to mortality: investigating the psychopath.
AB  - Various social animal species have been noted to inhibit aggressive attacks when
      a conspecific displays submission cues. Blair (1993) has suggested that humans
      possess a functionally similar mechanism which mediates the suppression of
      aggression in the context of distress cues. He has suggested that this mechanism
      is a prerequisite for the development of the moral/conventional distinction; the
      consistently observed distinction in subject's judgments between moral and
      conventional transgressions. Psychopaths may lack this violence inhibitor. A
      causal model is developed showing how the lack of this mechanism would explain
      the core behavioural symptoms associated with the psychopathic disorder. A
      prediction of such a causal model would be that psychopaths should fail to make
      the moral/conventional distinction. This prediction was confirmed. The
      implication of this finding for other theories of morality is discussed.

PMID- 7587018
TI  - Relevance theory explains the selection task.
AB  - We propose a general and predictive explanation of the Wason Selection Task
      (where subjects are asked to select evidence for testing a conditional "rule").
      Our explanation is based on a reanalysis of the task, and on Relevance Theory. We
      argue that subjects' selections in all true versions of the Selection Task result
      from the following procedure. Subjects infer from the rule directly testable
      consequences. They infer them in their order of accessibility, and stop when the
      resulting interpretation of the rule meets their expectations of relevance.
      Subjects then select the cards that may test the consequences they have inferred
      from the rule. Order of accessibility of consequences and expectations of
      relevance vary with rule and context, and so, therefore, does subjects'
      performance. By devising appropriate rule-context pairs, we predict that correct
      performance can be elicited in any conceptual domain. We corroborate this
      prediction with four experiments. We argue that past results properly reanalyzed
      confirm our account. We discuss the relevance of the Selection Task to the study
      of reasoning.

PMID- 7587019
TI  - Information gain explains relevance which explains the selection task.

PMID- 7587020
TI  - Cefotaxime in the 90's: A workshop for appropriate broad-spectrum cephalosporin
      utilization.

PMID- 7587021
TI  - Cefotaxime for the 1990s.

PMID- 7587022
TI  - Cefotaxime use in pediatric infections.
AB  - Cefotaxime has been used extensively in many pediatric centers in the United
      States for the past 10 or more years. Its main usage has been for the treatment
      of various serious bacterial infections in pediatric patients, primarily
      meningitis and sepsis. It has also been used to treat intraabdominal, urinary
      tract, soft tissue, bone, and joint infections. Although there has been a marked
      reduction in the incidence of invasive Haemophilus influenzae type b infections
      following the introduction of effective vaccines, cefotaxime remains very useful
      against the other common pathogens causing serious infections in pediatric
      patients. The increasing number of pneumococci resistant to penicillin and third
      generation cephalosporins has created a new challenge for the management of
      serious pneumococcal infections. In many institutions, cephalosporins in general
      have been overused and abused, resulting in the emergence of resistant organisms
      and an increasing burden on resources. The judicious use of cefotaxime and other
      cephalosporins should be emphasized.

PMID- 7587023
TI  - Cefotaxime for treatment of neonatal sepsis and meningitis.
AB  - Neonatal sepsis is a clinical syndrome characterized by systemic signs and
      symptoms, and bacteremia during the first month of life. The incidence is
      relatively low (one to eight cases/1000 live births), yet the risk of mortality
      is approximately 25%. Meningitis in the neonate is usually a sequela of
      bacteremia; however, it is discussed with neonatal sepsis, because they commonly
      share etiology and pathogenesis. The incidence of meningitis is usually a
      fraction of the number of infants with sepsis, varying in different settings from
      one-fourth to one-third. The mortality rate is high, varying in some series from
      15%-50%. There are two major forms of presentation of neonatal sepsis. Early
      onset disease presents as a fulminant, multisystemic illness during the first 5-7
      days of life; late-onset disease is more commonly recognized after the first
      weeks of life. Because different microorganisms are responsible for the two forms
      of disease, the choice of antimicrobial agents also differs. Some organisms such
      as Escherichia coli, group B streptococci, and Listeria monocytogenes may be
      responsible, whereas other pathogens such as Staphylococcus aureus and S.
      epidermidis, and Pseudomonas aeruginosa are usually associated with late-onset
      disease. Classic initial (empiric) treatment of neonatal sepsis and meningitis
      consists of ampicillin and an aminoglycoside. With the advent of the third
      generation cephalosporins, however, the empiric antimicrobial approach for
      neonatal sepsis and meningitis has changed in most centers. Third-generation
      cephalosporins cover more of the pathogens implicated in neonatal sepsis and
      meningitis, except for the enterococci and L. monocytogenes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7587024
TI  - Bactericidal activity of cefotaxime, desacetylcefotaxime, rifampin, and various
      combinations tested at cerebrospinal fluid levels against penicillin-resistant
      Streptococcus pneumoniae.
AB  - Penicillin resistance is increasingly prevalent amongst clinical isolates of
      Streptococcus pneumoniae. Recently, isolates resistant to the extended-spectrum
      cephalosporins have also begun to emerge, and combination therapy may be
      necessary for infection with such organisms. We have studied the activity of
      cefotaxime, ceftriaxone, ceftazidime, rifampin, chloramphenicol, and vancomycin
      against 10 S. pneumoniae strains with penicillin minimum inhibitory
      concentrations (MICs) ranging from 0.03-8 micrograms/ml. The bactericidal
      activity of cefotaxime, desacetylcefotaxime, rifampin, and combinations of these
      agents (cerebrospinal fluid levels) against these isolates was determined.
      Elevated MICs to penicillin were associated with generally twofold lower
      cefotaxime MICs. All strains remained susceptible to vancomycin and rifampin. The
      bactericidal activity of cefotaxime with or without desacetylcefotaxime was
      reduced by the addition of rifampin. Pneumococcal isolates with penicillin MICs
      of < or = 1 microgram/ml were slowly killed by cefotaxime alone or with
      desacetycefotaxime. At present, there is little evidence to support the addition
      of rifampin to cefotaxime for therapy of meningitis.

PMID- 7587025
TI  - Update on the use of cefotaxime for pediatric meningitis in Portugal.
AB  - We treated 256 children who had identified bacterial meningitis with cefotaxime.
      Causative organisms were: Neisseria meningitidis in 108 cases, Streptococcus
      pneumoniae in 61, Haemophilus influenzae in 60, enteric Gram-negative bacilli in
      21, and Staphylococcus spp. in six. Daily doses of cefotaxime were 150-200 mg/kg.
      A total of 240 patients (93.7%) were cured. In the cured patients, sterilization
      of cerebrospinal fluid was obtained in the first 72 h of treatment in 214
      (80.0%). Cefotaxime is an effective and safe drug for the treatment of childhood
      bacterial meningitis.

PMID- 7587026
TI  - Selection of cephalosporins for hospital formularies.
AB  - Because of the large number of cephalosporins available for use, and for economic
      reasons, most hospitals have restricted the number of cephalosporins for
      inclusion on hospital formularies. No more than one first-generation oral and
      parenteral cephalosporin is necessary. The second- and third-generation oral
      cephalosporins are more active in vitro against Haemophilus influenzae and
      Enterobacteriaceae, and the selection of one of these drugs should be based
      primarily on acquisition cost. There is usually minimal, if any, need for a
      second-generation parenteral cephalosporin on hospital formularies. The choice of
      a single third-generation parenteral cephalosporin should be made primarily on
      the cost of equivalent daily dosages. A single antipseudomonal cephalosporin
      should be included in the hospital formulary, and the selection should be based
      on cost and availability.

PMID- 7587027
TI  - The in vitro activity of cefotaxime versus bacteria involved in selected
      infections of hospitalized patients outside of the intensive care unit.
AB  - Cefotaxime, a parenteral third-generation cephalosporin in broad clinical use
      since the early 1980s, continues to possess extensive in vitro activity versus a
      variety of bacteria that are frequent causes of selected infections that commonly
      occur in hospitalized patients. Currently, bacteria with cefotaxime minimum
      inhibitory concentrations (MICs) of < or = 8 micrograms/ml are considered to be
      susceptible, and therefore amenable to treatment with cefotaxime at dosages of 2
      g intravenously (IV) every 6 or 8 h when causing monomicrobic infections in
      immunocompetent patients in whom adequate delivery of the drug to site(s) of
      infection can be assured. In fact, many common bacterial causes of infection
      typically have cefotaxime MICs 64 to 256-fold lower than the 8 micrograms/ml
      break point for susceptible. It is likely that selected monomicrobic infections
      in immunocompetent hospitalized patients due to such highly susceptible organisms
      could be treated with lower dosages of cefotaxime or with longer dosing intervals
      (e.g.,I g IV every 8-12 h or 2 g IV every 12 h. Examples of such infections
      include Gram-negative pneumonia outside of the intensive care unit setting,
      community-acquired pneumonia, skin and-soft tissue infections, pyelonephritis,
      and uncomplicated lower urinary tract infections.

PMID- 7587028
TI  - Retrospective analysis of the clinical and economic outcomes of twice-daily
      dosing of cefotaxime in a Canadian tertiary care institution.
AB  - A retrospective analysis of the clinical and economic outcome of a regimen of
      cefotaxime 1 g given every 12 h was conducted following the introduction of an
      institutional policy recommending this new dosing strategy. Patients were
      identified from a log order entry in the pharmacy, and the medical records were
      reviewed using a standardized data collection form. Explicit criteria were
      applied for the indications for antimicrobial therapy, presence of infection, and
      outcome parameters. A total of 60 patients with a mean (+/- SD) age of 56.2 (+/-
      17.8) years and a mean (+/- SD) length of stay of 20.75 (+/- 18.1) days were
      identified. Of these, 48 (80%) were found to have a clinically or
      microbiologically documented infection, and of the 42 patients who could be
      assessed accordingly to the criteria chosen, 37 (88%) had a favorable clinical
      response; 21 patients (35%) received cefotaxime alone. The costs for
      administration of cefotaxime have decreased by approximately 30% since the
      introduction of this new dosing regimen.

PMID- 7587030
TI  - Review and reassessment of dosing schedules for cefotaxime in selected medical
      indications.
AB  - Cefotaxime, the first widely used "third-generation" cephalosporin, has
      established efficacy against a variety of serious bacterial pathogens. Some of
      the initial clinical studies in the United States using this agent employed large
      doses of the compound, up to 12 g/day, for adults. In contrast, however, initial
      European studies were largely with low doses of 1 to 2 g every 12 h. In the
      recent past, however, an effort has been made, both in the United States and in
      Europe to reevaluate the dosage of cefotaxime. In various clinical studies, lower
      doses of cefotaxime have been successfully employed for infections of the urinary
      tract, peritoneum, biliary tract, lung, and skin and soft tissues. The results of
      a number of these studies will be reviewed, including a large postmarketing
      surveillance study carried out in Germany during 1992. The results suggest that
      cefotaxime doses as low as 1 g, at intervals as long as every 12 h, can be
      adequate for treatment of the most commonly encountered infections, such as those
      caused by some hemolytic streptococci, Staphylococcus aureus, Haemophilus spp.,
      and enteric bacilli in nonimmunocompromised patients.

PMID- 7587029
TI  - Experience with cefotaxime in the treatment of spontaneous bacterial peritonitis
      in cirrhosis.
AB  - Spontaneous bacterial peritonitis (SBP) is a severe infectious complication in
      cirrhotic patients, and initial antibiotic therapy must be empirical. An initial
      study published in 1985 found that cefotaxime administered at a dose of 2 g every
      4 h was more effective and safer than the combination of tobramycin-ampicillin.
      Since then, cefotaxime has been considered the agent of choice in the empiric
      therapy of SBP. Subsequent publications showed that a dosage of 2 g every 6 h was
      also adequate in this infection. More recent studies have demonstrated that the
      high efficacy of cefotaxime in SBP can be maintained by using lower dosages than
      those used in initial investigations. In one of these studies, a dose of 2 g
      every 8 h for 5 days was found to be as effective as the same dose for 10 days.
      Finally, a prospective, randomized multicenter trial aimed at comparing the
      efficacy of two different dosages of cefotaxime, 2 g every 6 h versus 2 g every
      12 in a large series of cirrhotic patients with SBP, showed that both dosages
      resulted in similar rates of resolution of infection and survival. Despite the
      reasonably adequate rate of infection resolution in SBP patients, the in-hospital
      mortality rate remains high as a result of complications such as renal failure.
      Further studies should therefore be addressed to reducing the incidence of these
      complications and thus improving survival.

PMID- 7587031
TI  - Cefotaxime twice daily versus ceftriaxone once daily. A randomized controlled
      study in patients with serious infections.
AB  - We randomized 365 patients with serious infections to treatment with either 2 g
      intravenously (IV) cefotaxime every 12 h or 2 g IV ceftriaxone once daily.
      Clinical response rates were similar in both treatment groups, with success
      defined as satisfactory or improved response in 107 of 124 (86.3%) evaluable
      patients in the cefotaxime group compared with 103 of 114 (90.4%) evaluable
      patients in the ceftriaxone group. Bacteriologic cure rates were also similar in
      the two groups (86.4%) in the cefotaxime group compared with 87.0% in the
      ceftriaxone group). There was no statistically significant difference in the
      incidence of drug-related adverse events in the two groups. These results
      indicate that 2 g cefotaxime twice daily is as effective, both clinically and
      bacteriologically, as 2 g ceftriaxone once daily in serious infections caused by
      susceptible pathogens.

PMID- 7587032
TI  - Prospective evaluation of twice-daily cefotaxime in the treatment of hospitalized
      patients with severe infections.
AB  - Cefotaxime 2 g every 12 h was administered to adults with severe nosocomial
      pneumonia in a prospective noncomparative study. The results confirmed that this
      regimen is adequate and appropriate therapy for nosocomial pneumonia, with the
      combination of cefotaxime and an aminoglycoside reserved for cases where
      multiresistant, Gram-negative bacterial infections are strongly suspected.

PMID- 7587033
TI  - Retrospective analysis of the efficacy of cefotaxime sodium dosed twice daily.
      The Swedish experience.
AB  - In a Swedish multicenter, comparative, retrospective study, patients with
      different types of infections--bacteremia-septicemia, genitourinary, intra
      abdominal, central nervous system, and lower respiratory tract infections--were
      randomly selected from the hospital records. Patients treated with cefotaxime
      twice or three times a day as monotherapy (excluding metronidazole) for at least
      1 day (240 cases) were analyzed in terms of clinical and bacteriologic outcome,
      these results were correlated with the dosing regimen. Similarly high success
      rates (cure and improvement) at hospital discharge were observed in both group
      initially treated with cefotaxime 1 g twice daily and 2 g twice daily (97 and
      96%, respectively). A total of 73% of patients were initially treated with
      cefotaxime for only 3 days at most before changing to a lower dose regimen, an
      alternate intravenous treatment, or oral drug follow-up. Clinical evaluation at
      hospital discharge revealed a clinical success rate between 87 and 100%,
      depending on the type of infection.

PMID- 7587034
TI  - A retrospective analysis of twice-daily cefotaxime compared to conventional
      therapy for the treatment of infections in a USA hospital.
AB  - A retrospective, matched cohort study was performed to determine the cost
      outcomes among 495 hospitalized patients who received twice-daily dosing of
      cefotaxime and 3949 matched cohorts who received other antibiotics. By an
      attribution model, twice-daily use was associated with shorter mean lengths of
      stay (-0.498 day, P < .7) and lower mean total costs of hospitalization (-$623, P
      < .8). Twice-daily dosing of cefotaxime is commonly employed for the treatment of
      a variety of serious infections, and appears to be cost effective.

PMID- 7587035
TI  - Cefotaxime versus ceftriaxone for the treatment of nosocomial pneumonia. Results
      of a multicenter study.
AB  - Third-generation cephalosporins are the drugs of choice for serious nosocomial
      pneumonia; however, the recommended dosages are controversial. Our study compared
      two of these cephalosporins and showed that 2 g cefotaxime every 12 h and 4 g
      ceftriaxone once daily or 2 g every 12 h proved to be effective therapies for
      these chest indications.

PMID- 7587036
TI  - The role of cefotaxime in the treatment of surgical infections.
AB  - This study examines the role of cefotaxime in the treatment of both Gram-negative
      and Gram-positive surgical infections. A dose of 2 g of cefotaxime will sustain
      peripheral compartment concentrations of 2.6, 3.9, 1.6, and 0.7 micrograms/ml for
      6, 8, 10 and 12 h, respectively. Therefore, the proportion of pathogens with a
      minimal inhibitory concentration (MIC) below the peripheral compartment
      cefotaxime concentrations was assessed as a measure of therapeutic potential. It
      was observed that bacterial elimination in infections correlates well with such
      pharmacodynamic predictions. Therefore, treatment recommendations for surgical
      infections are based on the following pharmacodynamics. The times above the MIC
      in the tissue compartment for various pathogens (1988-1994) known to cause
      surgical infections were: Escherichia coli, 12 h; all pyogenic streptococci, 12
      h; pneumococci, 12 h; Haemophilus spp., 12 h; Proteus mirabilis, 12 h; Klebsiella
      spp., 10.9 h; viridans streptococci, 10.6 h; oxacillin-susceptible, coagulase
      negative staphylococci, 9.7 h; Providencia spp., 9.2 h; Clostridium perfringens,
      8.6 h; Peptostreptococcus spp., 8 h; oxacillin-susceptible Staphylococcus aureus,
      7.3 h; and all S. aureus, 6.8 h. From the examination of pharmacodynamic
      parameters, cefotaxime appears to be a viable choice for the therapy of surgical
      infections other than the Gram-negative anaerobes. For those infections,
      metronidazole with cefotaxime would be preferred.

PMID- 7587037
TI  - Cefotaxime and metronidazole in severe intra-abdominal infection.
AB  - To assess the efficacy of cefotaxime in the treatment of severe intra-abdominal
      infections, we reviewed the bacteriology of secondary peritonitis and evaluated
      the efficacy of cefotaxime and metronidazole in 79 patients undergoing staged
      abdominal repair. We were able to demonstrate that the combination of an
      aggressive surgical policy with an effective antimicrobial regimen eliminates
      pathogens from the previously infected peritoneal cavity. Additional improvement
      in results awaits further advances in supportive care and/or methods to reverse
      the cascades of the excessive inflammatory or cytokine responses.

PMID- 7587038
TI  - Cephalosporin-metronidazole combinations in the management of intra-abdominal
      infections.
AB  - With our current understanding of antimicrobial pharmacokinetics and
      pharmacodynamics, optimal antimicrobial dosing strategies can be developed for a
      variety infectious processes. Herein, we discuss the clinical utility of a
      combination containing a third-generation cephalosporin plus metronidazole as
      compared to conventional single agents (cefoxitin and ampicillin-sulbactam) for
      the management intra-abdominal infections. At present, several studies have been
      performed that compare the bactericidal activity of such combinations to that of
      single agents for organisms commonly isolated from these intra-abdominal process.
      From these studies it appears that the use of a third-generation cephalosporin
      with strong activity against common aerobic organisms associated with intra
      abdominal infections in combination with a potent anaerobic drug such as
      metronidazole provides improved antibacterial activity and optimizes the
      pharmacodynamic profile of the agents over the dosing interval compared to
      conventional single agents. As a result of the pharmacokinetic and pharmaco
      dynamic superiority of the combination regimen, considerable pharmacoeconomic
      advantages may be realized with the clinical implementation of a third-generation
      cephalosporin plus metronidazole regimen. This approach should result in maximal
      clinical efficacy and is important not only for individual patient therapy, but
      also for formulary management decisions.

PMID- 7587039
TI  - Cefotaxime and desacetylcefotaxime antimicrobial interactions. The clinical
      relevance of enhanced activity: a review.
AB  - This presentation reviews 15 years of in vitro, pharmacokinetic, and clinical
      data concerning the active metabolite of cefotaxime sodium, desacetylcefotaxime.
      This principle metabolite maintains an antimicrobial activity and spectrum
      superior to so-called "second-generation" cephalosporins, plus it has an extended
      serum elimination half-life. Furthermore, it penetrates well into various
      important body compartments. The metabolite enhances cefotaxime potency by
      additive or synergistic antimicrobial interactions that can significantly reduce
      cefotaxime minimum inhibitory concentrations (MICs) among oxacillin-susceptible
      staphylococci, Streptococcus species including pneumococci resistant to
      penicillin, anaerobes, enteric bacilli, Pseudomonas aeruginosa, and when tested
      in human serum, some enterococci. The high activity of cefotaxime alone and the
      contributions of desacetylcefotaxime to the drug's total antimicrobial value must
      be considered in reestablishing correct dosing of this "third-generation"
      cephalosporin. Physicians should use cefotaxime susceptibility tests to direct
      appropriate, cost-effective dosing and the selection of co-drugs when needed.
      Moreover, empiric cefotaxime regimen doses should also be reduced for some
      infections at sites where expected pathogen MICs remain low (< or = 2
      micrograms/ml).

PMID- 7587040
TI  - Cefotaxime in the treatment of staphylococcal infections. Comparison of in vitro
      and in vivo studies.
AB  - Staphylococcus aureus strains are well-established pathogens that may cause mild
      to serious life-threatening disease. Coagulase-negative staphylococci,
      particularly Staphylococcus epidermidis, also have a pathogenic role in humans
      and cause infections primarily associated with prosthetic devices and indwelling
      catheters, whereas Staphylococcus saprophyticus usually causes urinary tract
      infections. Cefotaxime is a "third-generation" cephalosporin that is stable to
      the staphylococcal beta-lactamases. In vitro studies over the last 15 years have
      shown that this parenteral cephalosporin has remained highly active (MIC90 ranges
      of < or = 2-8 micrograms/ml) against oxacillin-susceptible staphylococci.
      Cefotaxime therapy of staphylococcal infections has resulted in clinical
      cure/improvement rates ranging from 78%-100% and bacteriologic eradication rates
      ranging from 85%-100% in a wide variety of infections. Contrary to contemporary
      dogma, this "third-generation" cephalosporin appears to be efficacious against
      staphylococcal infections from a review of 15 years of clinical experience.

PMID- 7587041
TI  - Study of cefotaxime twice daily for the therapy of postoperative pneumonia. The
      German Cefotaxime Study Group.
AB  - A total of 548 patients with postoperative pneumonia were treated with 1 or 2 g
      cefotaxime twice daily. Of the 88 patients without serious underlying diseases
      who received the 1-g 12-h dosage regimen, all were considered to be clinically
      cured, and all 54 isolated pathogens were eradicated or presumed to be
      eradicated. In the group with severe infection or severe underlying disease
      receiving 2 g 12-h cefotaxime, the overall clinical success rate (cured plus
      improved) was 98.4%. Results from this study support the use of cefotaxime as an
      alternative to empiric monotherapy for nosocomial pneumonia in surgical-service
      patients who are not neutropenic or on long-term artificial ventilation.

PMID- 7587042
TI  - Econotherapeutics.
AB  - A program that represents the efforts of a hospital pharmacy management company
      to control drug costs is described. The program, Econotherapeutics, was developed
      in response to a changed health care reimbursement system that focused on the
      costs of products rather than the revenue generated by these products. For
      antimicrobial agents, a hospital-specific antibiogram is used to encourage cost
      effective prescribing. A pharmacist intervention program, medical staff
      presentations, drug usage evaluation, management systems, and educational
      programs for pharmacists are all essential parts of the program. Centralized data
      gathering has allowed cost comparison of specific antimicrobial agents so that
      differences between variable cost estimates and costs based on actual use can be
      evaluated. Actual dose and dosage interval were used to calculate average cost
      per treatment day in a 121-hospital sample. Our cost data support the choice of
      cefotaxime over ceftriaxone.

PMID- 7587044
TI  - Pharmacoeconomics of appropriate antimicrobial use.
AB  - Pharmacoeconomics is founded on the key principle of economics, which is that
      society's resources are limited, and therefore, choices have to be made about the
      use of those resources. Pharmacoeconomic analysis should estimate the costs and
      consequences of different drug treatments, including the use of all health care
      resources, not drug costs alone. Application of these principles to appropriate
      antimicrobial treatment requires separate consideration of a sequence of
      questions: Who needs treatment? What are the best drug, dose, route of
      administration, and duration of therapy? What information do we have about the
      outcomes of treatment? None of these questions is easy to answer, but economic
      analysis will help the decision maker by making explicit the costs and
      consequences of the available alternatives.

PMID- 7587043
TI  - Switch therapy in community-acquired pneumonia.
AB  - In patients admitted to the hospital with community-acquired pneumonia,
      intravenous antimicrobials can be safely switched to oral administration when the
      patient shows evidence of early clinical improvement. In our institution,
      patients are switched to oral antibiotics when: (A) cough and respiratory
      distress are improving, (B) patient is afebrile for at least 8 h, (C) the white
      blood cell count is returning toward normal, and (D) there is no evidence of
      abnormal gastrointestinal absorption. Patients with respiratory infections of
      unknown etiology are switched to an oral antibiotic with the same spectrum of
      activity as the intravenous empiric antibiotic. Combining our prospective
      clinical studies, we have patient outcome data for more than 150 patients
      admitted to the hospital with community-acquired pneumonia, who were treated with
      switch therapy. The clinical cure rate was 99.3%. The total hospital savings for
      1994 based on the 80 patients with community-acquired pneumonia who were treated
      with switch therapy was $114,080. Discontinuation of intravenous lines will
      decrease the patient's risk for local cellulitis, abscess formation, septic
      thrombophlebitis, line sepsis, and endocarditis. The early hospital discharge
      associated with switch therapy will decrease the patient's risk for other
      nosocomial infections such as urinary or respiratory tract infections. Switch
      therapy is associated with a clinical cure rate that is equivalent to
      conventional therapy. In the area of cost-effective use of antibiotics, switch
      therapy should be considered as one of the primary options for health care cost
      containment.

PMID- 7587045
TI  - Cefotaxime and ceftriaxone use evaluation in pediatrics. Considerations of cost
      effectiveness.
AB  - In 1993, there was a change from ceftriaxone to cefotaxime in the inpatient
      pediatric division of the Johns Hopkins Hospital. The annual cost savings
      resulting from this change were estimated. The educational efforts of the
      pediatric division pharmacists resulted in an increase in appropriate drug
      selection from 55% to 93%. The estimated annual cost saving was $18,618.

PMID- 7587048
TI  - In vitro killing of penicillin-susceptible, -intermediate, and -resistant strains
      of Streptococcus pneumoniae by cefotaxime, ceftriaxone, and ceftizoxime: a
      comparison of bactericidal and inhibitory activity with achievable CSF levels.
AB  - This study assessed total microbial killing of 30 penicillin-susceptible, 
      intermediate, and -resistant strains of Streptococcus pneumoniae by cefotaxime,
      ceftriaxone, and ceftizoxime and compared these values with MICs for each strain
      against each agent as determined by three different methods/media. The results
      confirm the appropriateness of recent NCCLS recommendations for MIC interpretive
      criteria for third generation cephalosporins in which < or = 0.25 microgram/ml =
      susceptible and > or = 2.0 micrograms/ml = resistant when these agents are used
      to treat pneumococcal meningitis and data from total microbial killing studies
      suggests that most isolates with MICs of 0.5 and 1.0 mcg/ml would respond to high
      dose therapy with all three agents. The study also confirmed the recently
      described two- to four-fold decrease in activity of ceftizoxime against S.
      pneumoniae as compared with either cefotaxime or ceftriaxone; but noted that
      current NCCLS MIC interpretive criteria for the therapy of meningitis remain
      valid for all three agents. Finally, the study found that MICs determined by the
      E test or by microdilution broth methods using supplemented Todd Hewitt broth
      predict susceptibility as well as the NCCLS reference method. The actual
      selection among these agents for the therapy of pneumococcal meningitis should
      also consider other parameters including protein binding, age groups of clinical
      use, maximum potency against all clinically relevant pathogens, and cost.

PMID- 7587047
TI  - A team approach to hospital formulary replacement.
AB  - A multidisciplinary antibiotic review team (MART) was implemented to improve
      patient care and reduce antimicrobial expenditures. MART consists of pharmacists
      and infectious disease (ID) physicians reviewing patients three times weekly.
      Antibiotic expenditures were reduced by recommending conversions to
      therapeutically equivalent antibiotics, conversion to an oral agent, and
      completion of treatment with home infusion therapy. In addition, MART proposed
      therapeutic interchanges from ceftriaxone to cefotaxime to the P and T committee.
      ID physician or pharmacist offered recommendations and initiated order changes if
      the attending physician agreed. Annualized savings was $74,371, with 40% of the
      recommendations resulting in an improved antimicrobial therapy.

PMID- 7587049
TI  - Antimicrobial activity of cefotaxime tested against infrequently isolated
      pathogenic species (unusual pathogens).
AB  - The cefotaxime sodium spectrum of activity is very broad and includes many common
      species and a variety of less frequently isolated pathogens. We have reviewed the
      clinical microbiology literature (44 references) and the data base of the
      University of Iowa Hospitals and Clinics (Iowa City, IA) to collect data on the
      activity of cefotaxime against the less common species. Cefotaxime was
      consistently active against Actinobacillus actinomycetemcomitans, Capnocytophaga
      spp., Eikenella corrodens, Erysipelothrix rhusiopathiae, Pasteurella multocida,
      Plesiomonas shigelloides, and Fusobacterium nucleatum. The species Alcaligenes
      xylosoxidans, Flavobacterium spp., Stenotrophomonas (Xanthomonas) maltophilia,
      Bacillus cereus, Listeria monocytogenes, and Rhodococcus equi were uniformly
      cefotaxime resistant. For many other species there was considerable variation in
      reported minimum inhibitory concentrations. These data may be helpful in guiding
      therapy of unusual infections, particularly in the case of fastidious species,
      where the appropriate susceptibility testing methodology may not be immediately
      or routinely available.

PMID- 7587050
TI  - Pharmacokinetics of cefotaxime in healthy volunteers and patients.
AB  - Cefotaxime is a third-generation cephalosporin that has maintained good
      susceptibility pattern despite its extensive use. It is available for intravenous
      and intramuscular administration. Its pharmacokinetic property includes a small
      volume of distribution with low protein binding. Cefotaxime's half-life is
      approximately 1.1 h, and it is primarily eliminated by the kidney. It has an
      active metabolite desacetyl-cefotaxime that displays pharmacokinetic properties
      similar to cefotaxime. Desacetyl-cefotaxime has a half-life of 1.5 h and also is
      eliminated by the kidneys by both glomerular filtration and active secretion. The
      half-life of cefotaxime and its metabolite is altered in patients with severe
      renal dysfunction requiring dosage adjustment. Despite its relatively short half
      life, cefotaxime may be dosed every 12 h based on its pharmacokinetic and
      pharmacodynamic properties.

PMID- 7587046
TI  - Therapeutic exchange of cefotaxime for ceftriaxone: evaluation, implementation,
      and subsequent cost savings at a 300-bed community hospital.
AB  - Switching prescriptions from ceftriaxone to cefotaxime resulted in a decreased
      pharmacy expenditure of $30,190 within 1 year in a 300-bed community hospital.
      The cost per patient day of treatment was reduced from $38.85 to $26.98 and led
      to a total cost avoidance of $47,997.

PMID- 7587051
TI  - Cefotaxime. Unchanged antibacterial activity over years?
AB  - During recent years new mechanisms of beta-lactam resistance have developed with
      the genetic origin on the chromosome or plasmids. Nevertheless, most multicenter
      studies can demonstrate that cefotaxime has retained its antibacterial activity
      toward the relevant species. However, it is important to follow the development
      of resistance closely in hospitals, where epidemic outbreaks of bacterial strains
      with extended-spectrum beta-lactamases can create difficulties in the treatment
      of infectious diseases.

PMID- 7587052
TI  - Pharmacodynamic (kinetic) considerations in the treatment of moderately severe
      infections with cefotaxime.
AB  - Information about the pharmacodynamics of beta-lactams has accumulated rapidly
      over the last 20 years, and their application to cefotaxime are discussed in this
      review. Application of pharmacodynamics requires an integration of the
      pharmacokinetic and in vitro properties of the agent. Cefotaxime is similar to
      other beta-lactams in that it has little concentration-dependent killing and
      produces no postantibiotic effect against Gram-negative bacteria. However, it has
      a microbiologically active metabolite, deascetylcefotaxime, which can show
      synergy, partial synergy, or an additive effect in combination with the parent
      drug. More than any other technique, animal models have been able to elucidate
      the pharmacokinetic parameters that predict efficacy in vivo. They have shown
      that for beta-lactams it is the time that levels exceed the minimum inhibitory
      concentration (MIC) that is the most important determinant of efficacy. For
      bacteria to have no postantibiotic effect, plasma levels need to exceed the MIC
      for the whole of the dosing interval to achieve maximum killing at the site of
      infection. When applying these concepts as the most stringent criteria for
      efficacy using pharmacokinetic values from young, healthy volunteers, it can be
      shown that organisms with MICs of < or = 0.03 microgram/ml for a 1-g dose and
      0.06 microgram/ml for a 2-g dose to achieve optimum efficacy with 12-h dosing of
      cefotaxime. However, two clinical studies have demonstrated trough levels much
      greater than would be predicted from these pharmacokinetic values, as a result of
      the effects of decreased renal function accompanying sepsis and older age. These
      studies showed that organisms with MICs < or = 1 microgram/ml for a 1-g dose or 2
      micrograms/ml for a 2-g 12-h dose were covered for the whole of the dosing
      interval. Thus, all strains of Enterobacteriaceae and pathogenic Neisseria spp.
      that lack resistance mechanisms to third-generation cephalosporins would be
      covered using 12-h dosing schedules.

PMID- 7587053
TI  - Role of pharmacokinetics and pharmacodynamics in the design of dosage schedules
      for 12-h cefotaxime alone and in combination with other antibiotics.
AB  - Pharmacodynamic principles have provided important tools to evaluate and compare
      antimicrobial agents, and well as to guide dosing. For beta-lactams, time above
      the minimum inhibitory concentration (MIC) has surfaced as the most important
      factor. However, the area under the inhibitory serum concentration time-curve
      (AUIC) may be superior when appropriate dosing intervals are selected. Although
      the target time over the MIC is unclear in humans even when concentrations remain
      continuously above the MIC, a higher AUIC predicts better clinical outcome up to
      a maximum. This article provides a pharmacodynamic assessment of 1- and 2-g doses
      of cefotaxime every 12 h. AUIC24 values and published MIC values for common
      pathogens (grouped into four groups based on MIC90) were used to predict
      organisms suitable for treatment with every-12-h regimes. Cefotaxime was
      inadequate for group 4 organisms including: Pseudomonas aeruginosa,
      Acienetobacter sp., and Enterococcus sp. Organisms such as Enterobacter cloacae,
      Serratia marcescens, Staphylococcus aureus, and B. fragilis may be suboptimally
      treated with cefotaxime every 12 h. Cefotaxime in doses of 1-2 g every 12 h
      should be useful in patients with normal renal function infected with organisms
      having MICs < 0.5 microgram/ml. This regimen should obtain AUIC24 values > 125
      and ensure adequate time above the MIC. In patients with impaired renal function,
      because of a longer half-life and higher area under the curve, pathogens with MIC
      values in the 0.5-2 micrograms/ml range may be treated with cefotaxime every 12 h
      while maintaining AUICs > 125. Data are also presented for cefotaxime 2 g every 8
      h alone and in combination with ofloxacin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587054
TI  - Therapeutic options for cefotaxime in the management of bacterial infections.
AB  - Clinical studies of cefotaxime administered every 8 and 12 h have demonstrated
      comparable clinical and microbiologic success when compared to traditional 6-h
      regimens. This phenomena may be explained, in part, by the pharmacokinetic and
      pharmacodynamic properties of cefotaxime and the antimicrobially active
      metabolite desacetyl-cefotaxime. Although cefotaxime levels cannot be maintained
      above the bacterial minimum inhibitory concentration (MIC) for all infecting
      pathogens with extended dosing intervals, concentrations of desacetyl-cefotaxime
      remain above the effective concentration for a variety of organisms throughout
      the extended interval. Cefotaxime dosage adjustment may be accomplished in
      nonimmunocompromised patients with infections outside the central nervous system
      including uncomplicated urinary tract and lower respiratory infections.
      Infections caused by bacteria with MIC90 values < or = 1 microgram/ml usually
      respond to 8- or 12-h dosage intervals. Less susceptible organisms with MIC90
      values between 2 and 8 micrograms/ml, such as Serratia marcescens, may initially
      require cefotaxime administered every 6 or 8 h. Extended intervals should be
      avoided or used cautiously in patients that are neutropenic, immunocompromised,
      or hypermetabolic. Upon evidence of clinical and microbiologic response, therapy
      may be continued with alternative stepdown therapy.

PMID- 7587056
TI  - Interrelationship between pharmacokinetics and pharmacodynamics in determining
      dosage regimens for broad-spectrum cephalosporins.
AB  - The broad-spectrum cephalosporins exhibit time-dependent bactericidal activity
      and produce prolonged postantibiotic effects only with staphylococci. The
      duration of time that serum levels exceed the minimum inhibitory concentration
      (MIC) is the important pharmacodynamic parameter correlating with efficacy for
      these drugs. Maximal efficacy for cephalosporins in several animal infection
      models is approached when serum levels are above the MIC for 60%-70% of the
      dosing interval for Enterobacteriaceae and streptococci and for 40%-50% of the
      dosing interval for Staphylococcus aureus. Based on MIC90 values of 0.5
      microgram/ml for enteric bacilli and 4 micrograms/ml for S. aureus, these time
      above MIC goals can be easily met in infected and/or elderly patients following 1
      2 g of cefotaxime at 12-h intervals. Full knowledge of the interrelationships
      between pharmacokinetics and pharmacodynamics is important for determining
      effective dosage regimens for the broad-spectrum cephalosporins.

PMID- 7587055
TI  - Pharmacokinetics of cefotaxime in dialysis patients.
AB  - A literature review was carried out to assess the effect of hemodialysis,
      hemofiltration, and continuous ambulatory peritoneal dialysis on the
      pharmacokinetics of cefotaxime, particularly in patients with severe renal
      impairment. It was concluded that the dosage of cefotaxime, adjusted for renal
      function, would require no further adjustment during peritoneal dialysis or
      hemofiltration.

PMID- 7587057
TI  - Pharmacokinetics of cefotaxime and desacetylcefotaxime in the young.
AB  - Available information on the pharmacokinetics of cefotaxime (CTX) and
      desacetylcefotaxime (dCTX) indicates that their disposition depends on
      development, with the greatest changes occurring during the 1st year of life. To
      a great extent, these changes reside with the acquisition of renal function
      (e.g., both glomerular filtration and active tubular secretion) during the 1st
      year of life. When the impact of development on CTX and dCTX disposition is
      considered, it is apparent that age-appropriate pharmacokinetic data can be used
      to individualize CTX dosing regimens according to age. Also, alternative dosing
      regimens that have been proven to be both safe and effective can be justified.

PMID- 7587058
TI  - The cancer cell and the cell cycle clock.

PMID- 7587060
TI  - D-type cyclins and their cyclin-dependent kinases: G1 phase integrators of the
      mitogenic response.

PMID- 7587062
TI  - Functional analysis of the TAN-1 gene, a human homolog of Drosophila notch.

PMID- 7587064
TI  - Ras signal transduction pathway in Drosophila eye development.

PMID- 7587059
TI  - The Max transcription factor network: involvement of Mad in differentiation and
      an approach to identification of target genes.
AB  - The small bHLHZip protein, Max, was originally identified through its interaction
      with Myc family proteins and appears to be an obligate partner for Myc function.
      Max has now been found to interact with at least two other proteins, Mad and
      Mxi1. These also belong to the bHLHZip class but are otherwise unrelated to Myc.
      Mad has been shown to abrogate the positive transcriptional activity of Myc and
      to inhibit Myc in co-transformation assays. This suggests that Mad may antagonize
      Myc function. Mad is rapidly induced upon differentiation, a time when Myc is
      frequently down-regulated. We show here evidence for Mad expression upon
      differentiation of myeloblasts, monoblasts, and keratinocytes. Mad:Max complexes
      are detected during differentiation and appear to replace the Myc:Max complexes
      present in proliferating cell populations. Since these complexes appear to form
      even in the presence of Myc, there may exist mechanisms that act to inhibit
      Myc:Max, or to promote Mad:Max, complex formation. We speculate that Max complex
      switching causes a change in the transcriptional activity of groups of target
      genes. Mad is not induced in all differentiating cell types, suggesting that
      other, possibly tissue-restricted, proteins might act in similar switch
      mechanisms to effect changes in transcriptional programs. We have also developed
      an approach to identification of the gene targets for Myc:Max complexes. By
      employing an immunoisolation procedure, we have begun characterization of several
      clones whose expression levels correlate with those of c-myc. Further
      identification of Myc-regulated genes may allow us to determine the molecular
      mechanism by which Myc governs cell proliferation and differentiation.

PMID- 7587061
TI  - BCL-6 and the molecular pathogenesis of B-cell lymphoma.
AB  - The results presented identify the first genetic lesion associated with DLCL, the
      most clinically relevant form of NHL. Although no proof yet exists of a role for
      these lesions in DLCL pathogenesis, the feature of the BCL-6 gene product, its
      specific pattern of expression in B cells, and the clustering of lesions
      disrupting its regulatory domain strongly suggest that deregulation of BCL-6
      expression may contribute to DLCL development. A more precise definition of the
      role of BCL-6 in normal and neoplastic B-cell development is the goal of ongoing
      study of transgenic mice engineered either to express BCL-6 under heterologous
      promoters or lacking BCL-6 function due to targeted deletions. In addition to
      contributing to the understanding of DLCL pathogenesis, the identification of BCL
      6 lesions may have relevant clinical implications. DLCL represent a heterogeneous
      group of neoplasms which are treated homogeneously despite the fact that only 50%
      of patients experience long-term disease-free survival (Schneider et al. 1990).
      The fact that BCL-6 rearrangements identify biologically and clinically distinct
      subsets of DLCL suggests that these lesions may be useful as markers in selection
      of differential therapeutic strategies based on different risk groups.
      Furthermore, the BCL-6 rearrangements can be used to identify and monitor the
      malignant clone with sensitive PCR-based techniques. Since clinical remission has
      been observed in a significant fraction of DLCL cases, these markers may serve as
      critical tools for sensitive monitoring of minimal residual disease and early
      diagnosis of relapse (Gribben et al. 1993).

PMID- 7587063
TI  - Novel oncogenic mutations in the WT1 Wilms' tumor suppressor gene: a t(11;22)
      fuses the Ewing's sarcoma gene, EWS1, to WT1 in desmoplastic small round cell
      tumor.
AB  - These studies suggest that the WT1 tumor suppressor gene, originally identified
      as a recessive oncogene in Wilms' tumors, is capable of sustaining a gain-of
      function mutation which results in its contribution to a completely different
      disease entity: desmoplastic small round cell tumor. Two independent biochemical
      functions of WT1, DNA-binding activity and mode of transcriptional regulation,
      are altered as a consequence of the chromosomal translocation and fusion with
      EWS. The fusion of EWS and WT1 genes in DSRCT thus provides a unique paradigm for
      a means by which different alterations of transcription factor function can lead
      to diverse oncogenic processes.

PMID- 7587066
TI  - Proto-oncogenes and plasticity in cell signaling.

PMID- 7587068
TI  - Ras partners.

PMID- 7587067
TI  - Activation of Ras and other signaling pathways by receptor tyrosine kinases.

PMID- 7587069
TI  - Proteins of the 14-3-3 family associate with Raf and contribute to its
      activation.

PMID- 7587065
TI  - Molecular genetics of proto-oncogenes and candidate tumor suppressors in
      Caenorhabditis elegans.

PMID- 7587070
TI  - Regulation of the cryptic sequence-specific DNA-binding function of p53 by
      protein kinases.
AB  - p53 is an allosterically regulated protein with a latent DNA-binding activity.
      Posttranslational modification of a carboxy-terminal regulatory site in vitro, by
      casein kinase II and protein kinase C, can activate the sequence-specific DNA
      binding function of the wild-type protein. The latent form of p53 is produced in
      a variety of eukaryotic and prokaryotic cell lines, including E. coli, Sf9 insect
      cells, and C6 cells, indicating that the activation of p53 in vivo is rate
      limiting. In addition, phosphorylation of p53 at the protein kinase C site and
      activation in vivo correlate with the loss of reactivity of active p53 protein to
      the carboxy-terminal antibody, PAb421. These results suggest that two highly
      conserved protein kinases modify polypeptide structure through a common
      biochemical mechanism and that different enzymatic pathways may channel
      information into the carboxy-terminal regulatory site of p53, allosterically
      activating its function as a tumor suppressor.

PMID- 7587071
TI  - DNA-binding properties of the p53 tumor suppressor protein.

PMID- 7587072
TI  - p21 is a component of active cell cycle kinases.

PMID- 7587073
TI  - Functions of the p53 protein in growth regulation and tumor suppression.

PMID- 7587075
TI  - E6-AP directs the HPV E6-dependent inactivation of p53 and is representative of a
      family of structurally and functionally related proteins.

PMID- 7587074
TI  - Targets for transcriptional activation by wild-type p53: endogenous retroviral
      LTR, immunoglobulin-like promoter, and an internal promoter of the mdm2 gene.

PMID- 7587076
TI  - p53-dependent apoptosis in vivo: impact of p53 inactivation on tumorigenesis.

PMID- 7587077
TI  - Cell cycle checkpoints, genomic integrity, and cancer.

PMID- 7587080
TI  - Lymphocyte-specific genetic instability and cancer.

PMID- 7587078
TI  - Genomic integrity and the genetics of cancer.

PMID- 7587079
TI  - DNA damage responses: p53 induction, cell cycle perturbations, and apoptosis.

PMID- 7587081
TI  - Cell cycle checkpoint control is bypassed by human papillomavirus oncogenes.

PMID- 7587083
TI  - Cyclins, Cdks, and cyclin kinase inhibitors.

PMID- 7587082
TI  - Telomerase, cell immortality, and cancer.

PMID- 7587085
TI  - Human mismatch repair genes and their association with hereditary non-polyposis
      colon cancer.

PMID- 7587084
TI  - Three unusual repair deficiencies associated with transcription factor
      BTF2(TFIIH): evidence for the existence of a transcription syndrome.

PMID- 7587088
TI  - Loss of imprinting in human cancer.

PMID- 7587087
TI  - Ovarian tumors display persistent microsatellite instability caused by mutation
      in the mismatch repair gene hMSH-2.

PMID- 7587086
TI  - Defects in replication fidelity of simple repeated sequences reveal a new mutator
      mechanism for oncogenesis.

PMID- 7587089
TI  - Enhanced cell survival and tumorigenesis.

PMID- 7587090
TI  - The genetics of programmed cell death in the nematode Caenorhabditis elegans.

PMID- 7587091
TI  - Bcl-2 gene family and the regulation of programmed cell death.

PMID- 7587093
TI  - Control of p53-dependent apoptosis by E1B, Bcl-2, and Ha-ras proteins.

PMID- 7587092
TI  - Role of a cell cycle regulator in hereditary and sporadic cancer.

PMID- 7587094
TI  - Apoptosis in carcinogenesis: the role of p53.

PMID- 7587097
TI  - Transgenic approaches to the analysis of ras and p53 function in multistage
      carcinogenesis.

PMID- 7587099
TI  - Tumorigenic and developmental effects of combined germ-line mutations in Rb and
      p53.

PMID- 7587096
TI  - Apoptosis and the prognostic significance of p53 mutation.

PMID- 7587098
TI  - Mouse model systems to study multistep tumorigenesis.

PMID- 7587100
TI  - Insulin-like growth factor II is focally up-regulated and functionally involved
      as a second signal for oncogene-induced tumorigenesis.

PMID- 7587095
TI  - Cellular senescence and cancer.

PMID- 7587101
TI  - Angiostatin: a circulating endothelial cell inhibitor that suppresses
      angiogenesis and tumor growth.

PMID- 7587102
TI  - The p53 tumor suppressor gene inhibits angiogenesis by stimulating the production
      of thrombospondin.

PMID- 7587103
TI  - p16INK4 mutations and altered expression in human tumors and cell lines.

PMID- 7587105
TI  - The adenomatous polyposis coli gene of the mouse in development and neoplasia.

PMID- 7587107
TI  - Colorectal cancer and the intersection between basic and clinical research.

PMID- 7587104
TI  - Defining the steps in a multistep mouse model for mammary carcinogenesis.

PMID- 7587108
TI  - Green pigs, red herrings, and a golden hoe: a retrospective on the identification
      of BRCA1 and the beginning of its characterization.

PMID- 7587106
TI  - Genetic instability and apoptotic cell death during neoplastic progression of v
      myc-initiated B-cell lymphomas in the bursa of Fabricius.

PMID- 7587109
TI  - Progress toward isolation of a breast cancer susceptibility gene, BRCA1.
AB  - The high incidence of breast cancer and/or ovarian cancer in some families
      appears to be due to germ-line mutations in BRCA1. Genetic analysis of such
      families suggests that the BRCA1 candidate region lies between D17S857 and D17S78
      on chromosome 17q21 (Kelsell et al. 1993; Simard et al. 1993). To identify and
      isolate BRCA1, we have used linkage and meiotic recombination analysis,
      characterized regions displaying LOH in tumor DNA from BRCA1-linked families,
      performed YAC and cosmid clone isolation and ordering, and used three
      complementary transcript-searching strategies. We have identified as many as 28
      genes from the BRCA1 candidate region, and we are searching for constitutive
      mutations in these candidate genes by several methods in an attempt to identify
      BRCA1.

PMID- 7587110
TI  - RNA genetics of breast cancer: maspin as paradigm.

PMID- 7587113
TI  - Molecular genetic changes found in human lung cancer and its precursor lesions.

PMID- 7587111
TI  - Acute myeloid leukemia with Inv (16) produces a chimeric transcription factor
      with a myosin heavy chain tail.

PMID- 7587114
TI  - Molecular characterization of QM, a novel gene with properties consistent with
      tumor suppressor function.

PMID- 7587112
TI  - Genetic alterations in the chromosome 22q12 region associated with development of
      neuroectodermal tumors.

PMID- 7587115
TI  - Barrett's esophagus: a model of human neoplastic progression.

PMID- 7587116
TI  - Detection of genetic loss in tumors by representational difference analysis.

PMID- 7587118
TI  - Molecular genetic approaches to the study of cellular senescence.
AB  - Cellular senescence is an inability of cells to synthesize DNA and divide, which
      results in a terminal loss of proliferation despite the maintenance of basic
      metabolic processes. Senescence has been proposed as a model for the study of
      aging at the cellular level, and the basis for this model system and its features
      have been summarized. Although strong experimental evidence exists to support the
      hypothesis that cellular senescence is a dominant active process, the mechanisms
      responsible for this phenomenon remain a mystery. Investigators have taken
      several approaches to gain a better understanding of senescence. Several groups
      have documented the differences between young and senescent cells, and others
      have identified changes that occur during the course of a cell's in vitro life
      span. Using molecular and biochemical approaches, important changes in gene
      expression and function of cell-cycle-associated products have been identified.
      The active production of an inhibitor of DNA synthesis has been demonstrated.
      This may represent the final step in a cascade of events governing senescence.
      The study of immortal cells which have escaped senescence has also provided
      useful information, particularly with regard to the genes governing the
      senescence program. These studies have identified four complementation groups for
      indefinite division, which suggests that there are at least four genes or gene
      pathways in the senescence program. Through the use of microcell-mediated
      chromosome transfer, chromosomes encoding senescence genes have been identified;
      efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587117
TI  - Genetic approaches to defining signaling by the CML-associated tyrosine kinase
      BCR-ABL.

PMID- 7587119
TI  - The AML1 gene in the 8;21 and 3;21 translocations in chronic and acute myeloid
      leukemia.

PMID- 7587120
TI  - Expression of P-glycoprotein in normal and malignant rat liver cells.

PMID- 7587122
TI  - Pathogenesis of cancer of the cervix.

PMID- 7587121
TI  - Genes coding for tumor-specific rejection antigens.

PMID- 7587124
TI  - Studies of the deleted in colorectal cancer gene in normal and neoplastic
      tissues.
AB  - Chromosome 18q is among the chromosomal regions thought to harbor a tumor
      suppressor gene(s) that is frequently inactivated during the development of
      several cancer types, particularly those of the gastrointestinal tract. Moreover,
      preliminary data suggest that colorectal cancers with 18q LOH have a more
      aggressive clinical behavior than those cancers without 18q LOH. A candidate
      tumor suppressor gene from 18q, termed DCC for deleted in colorectal cancer, has
      been identified. The DCC gene is contained within the common region of LOH on
      18q, its expression is markedly decreased or absent in colorectal cancers and
      cell lines, and a subset of colorectal cancers have been shown to have somatic
      mutations within the DCC gene. Thus, DCC represents the most promising candidate
      tumor suppressor gene from 18q. At present, however, many questions remain
      regarding the mechanisms underlying the inactivation of DCC in the majority of
      colorectal cancers. In addition, although studies of 18q LOH and DCC gene
      expression in other cancer types suggest that DCC inactivation may contribute to
      the pathogenesis of other tumor types, few studies have provided definitive data
      to demonstrate that DCC inactivation is a critical genetic event in these tumors.
      Moreover, little is known about the function of DCC in the regulation of normal
      cell growth and tumor suppression. The predicted structural similarity of DCC to
      the N-CAM family of cell-surface proteins suggests that it may function through
      cell-cell and/or cell-extracellular matrix interactions.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7587125
TI  - Molecular cytogenetics of human breast cancer.
AB  - Our studies of human breast cancer using CGH and FISH with precisely mapped
      probes have revealed a surprising amount of intratumor and intertumor
      heterogeneity in human breast cancers. However, some regions of abnormal copy
      number are found frequently. We believe that the regions of frequent abnormality
      harbor novel cancer genes, and that identification of these is important for
      diagnosis, prognostication, and the development of new therapies.

PMID- 7587123
TI  - Autocrine mechanism for met proto-oncogene tumorigenicity.

PMID- 7587127
TI  - Multicellular resistance: a new paradigm to explain aspects of acquired drug
      resistance of solid tumors.

PMID- 7587129
TI  - Overcoming complexities in genetic screening for cancer susceptibility.

PMID- 7587126
TI  - Genetic alterations in prostate cancer.
AB  - A number of genetic changes have been documented in prostate cancer, ranging from
      allelic loss to point mutations and changes in DNA methylation patterns
      (summarized in Fig. 1). To date, the most consistent changes are those of allelic
      loss events, with the majority of tumors examined showing loss of alleles from at
      least one chromosomal arm. The short arm of chromosome 8, followed by the long
      arm of chromosome 16, appear to be the most frequent regions of loss, suggesting
      the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and
      p53 genes are less frequent, as are mutations of the p53 gene, and accumulating
      evidence suggests the presence of an additional tumor suppressor gene on
      chromosome 17p, which is frequently inactivated in prostate cancer. Alterations
      in the E-cadherin/alpha-catenin-mediated cell-cell adhesion mechanism appear to
      be present in almost half of all prostate cancers and may be critical to the
      acquisition of metastatic potential of aggressive prostate cancers. Finally,
      altered DNA methylation patterns have been found in the majority of prostate
      cancers examined, suggesting widespread alterations in methylation-modulated gene
      expression. The presence of multiple changes in these tumors is consistent with
      the multistep nature of the transformation process. Finally, efforts to identify
      prostate cancer susceptibility loci are under way and may elucidate critical
      early events in prostatic carcinogenesis.

PMID- 7587128
TI  - Molecular and cell biology of replicative senescence.

PMID- 7587130
TI  - Exploiting multidrug resistance to treat cancer.

PMID- 7587132
TI  - Gene transfer and bone marrow transplantation.

PMID- 7587131
TI  - Toxicity and immunologic effects of in vivo retrovirus-mediated gene transfer of
      the herpes simplex-thymidine kinase gene into solid tumors.

PMID- 7587133
TI  - Molecular genetic interventions for cancer.

PMID- 7587134
TI  - Growth suppression by members of the retinoblastoma protein family.

PMID- 7587135
TI  - The adenovirus E1A-associated 300-kD protein exhibits properties of a
      transcriptional coactivator and belongs to an evolutionarily conserved family.

PMID- 7587136
TI  - The corral hypothesis: a novel regulatory mode for retinoblastoma protein
      function.

PMID- 7587137
TI  - Lexical and sublexical feedback in auditory word recognition.
AB  - Currently, there are two qualitatively different model classes in the field of
      spoken language understanding. Autonomous models allow only bottom-up information
      flow, whereas interactive models allow higher level representations (e.g.,
      lexical) to affect processing at lower levels (e.g., phonemic). Part 1 of the
      present study included a test of a prediction that differentiates the two model
      classes: Is phoneme monitoring faster for targets in real words than in
      pseudowords, even before the word could in principle be recognized? The results
      indicate that this lexical advantage does occur, in accord with the predictions
      of interactive models. In Part 2, speech compression and expansion were used to
      assess the sufficiency or necessity of bottom-up evidence and of processing time
      in accomplishing lexical access. The results of Parts 1 and 2 suggested that in
      addition to the lexical effects posited by current models, sublexical activation
      may also play an important role. Data are presented in Part 3 that support this
      interpretation. Collectively, the results in the current study support
      interactive models of lexical processing, but require additional sublexical
      processes as well.

PMID- 7587138
TI  - Caries treatment through 30 years in children and adolescents in Asker, Norway.
AB  - Asker is a capital suburb where a preventive philosophy has guided the public
      dental health services for decades. In the period studied the child population
      aged 3-13 yr increased from 3208 to 6008. In the school age groups 7-15 yr
      practically all children in the community have participated in the dental service
      programs. The objective of the paper is to present retrospectively the changes in
      caries status of children under near optimal dental health care conditions and to
      expose reported preventive activities. A considerable increase in the proportion
      of "caries free" pre-school children occurred in the period 1976-88. A maximum
      was reached in the latter part of the eighties, whereafter a leveling off is
      suggested. For school children a rapid increase in "caries free" children took
      place for the lowest grades, starting before 1976. The higher grades came later
      and at a slower pace. The great number of fillings inserted in 1966-72,
      oscillating around 60 surfaces for the nine school years, decreased rapidly
      during the following decade and seems now to have settled around a total average
      of five to six surfaces. This implies a reduction of 90% in 20 yr. In most age
      groups these changes started before 1970. The major part of the caries decline
      occurred in the seventies and a leveling off is apparent during the eighties. The
      average number of filled surfaces per year has fallen from 6.6 in the 1955 birth
      cohort to 0.7 in the 1977 cohort, a reduction of 89% in 22 yr.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7587139
TI  - Relationship between gap width and recurrent dental caries beneath occlusal
      margins of amalgam restorations.
AB  - This study examines the relationship between gap width and the presence of
      recurrent dental caries subjacent to occlusal margins of amalgam restorations.
      The study population consisted of 35 adult patients of the university's dental
      clinic who were having occlusal amalgam restorations removed solely because of
      defective margins. In this group, an impression was made recording the width of a
      clinically detected gap between the amalgam restoration and the adjacent enamel
      cavosurface. Of this study population, 20 teeth with recurrent caries were
      identified from 18 subjects after restoration removal. Upon removal of the
      restoration, the presence and location of recurrent dental caries associated with
      a margin was noted. The mean gap widths of recurrent carious sites and non
      carious sites were compared in the same tooth. A difference of 187 microns was
      found between the mean gap width of the recurrent caries sites and the non
      carious sites, with the recurrent caries gaps being wider. A paired t-test based
      on the differences was calculated (P < 0.0001). The results suggest that there is
      a direct association between gap width and recurrent caries in occlusal margins
      of amalgam restorations.

PMID- 7587140
TI  - Relationship between dental caries and risk factors for atherosclerosis in
      Swedish adolescents?
AB  - In an earlier study on a selected group of adolescents with high caries
      prevalence we found dietary habits that resembled those considered to promote the
      development of atherosclerosis. In the present study we have compared DMF-score
      with factors traditionally associated with the risk for development
      cardiovascular diseases (CVD). All 15-yr-olds living in an urban community in
      Northern Sweden 1987-1989 were included. Medical variables related to the risk of
      developing CVD were evaluated in groups of adolescents with various levels of
      manifest caries expressed as decayed and filled surfaces (DFS). The proportion of
      individuals with no medical risk factor at an unfavorable level was significantly
      higher in a caries free than in a high-caries (DFS > or = 9) group. Adolescents
      with two or more medical factors reaching unfavorable levels had a significantly
      higher caries score than the group with no factor at unfavorable level. A
      significant positive correlation was found for the whole group between DFS-score
      and relative body weight (body mass index) in an univariate correlation test as
      well as multiple linear regression analysis. The hypothesis that high caries
      score can be an indicator for unfavorable levels of traditional risk factors for
      CVD is not contradicted by the results in the present study but supported by the
      observed covariation with BMI. We therefore suggest that dietary counseling to
      adolescents with a high caries score in combination with a moderate obesity can
      be of advantage in reducing the caries risk as well as the risk for development
      of CVD at higher ages.

PMID- 7587141
TI  - Radiographic study of approximal restorative treatment in children and
      adolescents in two Swedish communities differing in caries prevalence.
AB  - In two groups of patients, differing in caries prevalence, the restorative
      treatment of posterior approximal surfaces in permanent teeth was studied in
      radiographs obtained as part of the dental care provided from age 6 up to and
      including age 18. The study determined at what age, at which lesion depth and in
      which surfaces restorative treatment was performed. Furthermore, the conditions
      of nonrestored dentin lesions were evaluated over time. Nearly 50% of the
      restorations were placed in the mesial surface of the first molars. In both
      groups more than 2/3 of the restorations were placed in surfaces with dentin
      lesions. In the group with the highest caries prevalence 50% of the lesions in
      the outer half of the dentin were restored when first detected in contrast to 20%
      in the groups with the lower prevalence. For the superficial dentin lesions not
      immediately restored, average time between their detection and restoration, the
      end of the study or, detection in the inner half of the dentin was practically
      the same in both groups (19.3 and 20.4 months). The variation in this average
      time was only to a limited degree explained by the variation in the caries
      experience of the patients.

PMID- 7587142
TI  - Concentrations of blood, serum and urine components in relation to number of
      amalgam tooth fillings in Swedish women.
AB  - Altogether 1462 women aged 38, 46, 50, 54 and 60 yr were examined in 1968/69 in a
      combined medical and dental population study in Gothenburg, Sweden. Number of
      tooth surfaces restored with amalgam fillings was assessed. The examination was
      repeated in 1980/81 including a new dental examination. The results from a number
      of biochemical analyses of blood, serum and urine were analyzed for a possible
      statistical relationship to number of dental amalgam fillings. As emphasis has
      been put in the literature on special influence from amalgam on kidney function
      and on the immunological system, special attention was paid to variables which
      might reflect these functions in our analyses. When potential confounders were
      taken into consideration, no significant correlations remained which seemed to be
      of clinical importance. Specifically, amalgam fillings were not found to be
      associated with impairment of the kidney function or the immunological status.

PMID- 7587143
TI  - Comparing dental utilization of U.S. Army soldiers with their employed civilian
      cohorts.
AB  - In fall 1992, a random, worldwide sample of 5474 enlisted and 4036 officer,
      active duty, U.S. Army personnel was surveyed on dental utilization. Overall
      survey response rate was 62%. After weighting the data to reflect the population,
      dental utilization rates of military personnel were compared with their employed
      civilian cohorts in the U.S. population. Results show that, regardless of race or
      gender, over 80% of U.S. Army personnel have seen a dentist within the past year.
      Controlling for age, gender, and race, active duty U.S. Army personnel have
      dental utilization rates that greatly exceed their employed civilian cohorts. The
      results suggest that access barriers to dental care present in the civilian
      population, especially for minorities, are greatly diminished in the U.S. Army.
      The results suggest that access to free care may be a potent stimulus to
      utilization of dental services among military or civilian personnel. Further,
      access to free dental care should be emphasized in recruiting and retaining U.S.
      military personnel.

PMID- 7587144
TI  - Dental care of infectious patients in Denmark, 1986-1993: theoretical
      considerations and empirical findings.
AB  - Changes in infection control and behavior and attitudes towards HIV-infected
      patients from 1986 to 1992/93 were studied among a random sample of 335 Danish
      dentists; previous studies among random samples of Danish dentists served as
      references. 249 (74.3%) returned a mailed questionnaire together with a time,
      steam, temperature (TST) control indicator strip processed in their steam
      autoclaves, 3.4% of the autoclaves had not sterilized properly, which was an
      insignificant decrease compared to 1986. Overall, infection control had improved
      since 1986. In 1992/93 17.3% of dentists surveyed reported use of gloves always:
      in 1986 0.8% did so. Many (60.2%) reported at least one needlestick or cut
      accident within the last year. The number of dentists who were willing to treat
      HIV-infected patients and the number of clinics that found they could treat
      infectious patients safely had increased from 56.1% to 78.7% and from 43.0% to
      66.8%, respectively. Other attitudinal dimensions, for example views on secrecy
      of HIV test results and HIV screening policy, had not changed. A conceptual model
      based on the theory of reasoned action formed the framework for multiple logistic
      regression analysis with two different outcomes: Willingness to treat HIV
      infected individuals and Treatment of HIV-infected patients. In particular,
      expected staff problems turned out to have a high explanatory value (odds ratio =
      18.2) if HIV-infected patients were received. In both models Certainty about
      hygienic precautions had some explanatory value. The findings may give some clues
      about how to plan and implement future continuing education on infection control
      and attitudinal and behavioral aspects of caring for infectious patients.

PMID- 7587147
TI  - Prevalence and severity of dental fluorosis in a Mexican community with above
      optimal fluoride concentration in drinking water.
AB  - The purpose of this study was to determine the prevalence and severity of dental
      fluorosis in children living in a community at 2066 m above sea level. The water
      fluoride concentration of this community was 2.8 ppm. The population selected
      encompassed 10-12-yr-old schoolchildren who were life-long residents of the area.
      The modified Dean Index was used to estimate the severity of fluorosis. A total
      of 93 children participated in the study. They all showed evidence of dental
      fluorosis. Fifty-seven percent had moderate fluorosis, and 19% severe fluorosis.
      The high prevalence and severity of fluorosis in the population examined
      emphasized the need to study the factors determining dental fluorosis in Mexican
      communities.

PMID- 7587145
TI  - Prognosis of and factors associated with dental status in the adult Swedish
      population, 1975-1989.
AB  - The aim was to describe changes in dental status in the Swedish population during
      the period 1975-89 and to make a prognosis based on these data for the year 2000.
      This study is based on investigations of the living conditions in 1975, 1977,
      1980/81 and 1988/89 performed by The National Central Bureau of Statistics. The
      samples varied for each year from 11,500 to 15,000 participants and a response
      rate from 80 to 86%. The odontological questions of the interview were focused on
      dental status, utilization of dental services and chewing ability. The prevalence
      of edentulism in age group 16-74 yr decreased from 15% in 1975 to 6% in 1988/89.
      In 1988/89 19% of the 65-74-yr-old inhabitants of the big cities were edentulous
      and 45% in rural populations, indicating a 15-20-yr delay of the development in
      rural areas. The prognosis for the year 2000 indicates a further decrease of
      edentulism to 3-4% in age groups 45-64 yr and in age 75-84 yr more than 60% will
      be dentate. As a consequence of the reduction in edentulism and changes in
      populations the number of dentate inhabitants in age group 25-74 yr increased by
      about 800,000 from 1975 to 1989 and a further increase of 400,000 will occur up
      to the year 2000. The consequences of these changes for the dental care services
      are discussed.

PMID- 7587146
TI  - Periodontal attachment loss among adults aged 60+ in South Australia.
AB  - This study aimed to provide oral epidemiological data describing periodontal
      destruction among older adults in South Australia. A cross-sectional survey
      design was employed and periodontal assessments were made among 801 persons aged
      6+ drawn at random from the non-institutionalized population. Measurements of
      pocket depth (PD) and gingival recession (GR) were made at three sites on all
      teeth and used to compute loss of attachment (LOA). An average of 17 teeth per
      person were measured. LOA of 4+ mm at one or more sites was observed among 89.1%
      of persons. A mean of 78.1% of sites per person had LOA of 2+ mm (extent) and the
      mean LOA at sites with LOA of 2+ mm was 3.09 mm (severity). Extent and severity
      were greater for males and for persons aged 80+ years. Extent was virtually
      identical for mesio-buccal and disto-lingual sites, while severity was virtually
      identical for mid-buccal and disto-lingual sites. Patterns of GR and PD varied
      according to the jaw and type of tooth. Maxillary first and second molars had the
      greatest mean LOA, and the majority of LOA in the maxilla was due to PD. In the
      mandible there was less variation in LOA among anterior and posterior teeth, and
      LOA tended to be more equally divided between GR and PD. Levels of periodontal
      destruction of South Australia were broadly similar to results from North
      American studies of older adults which have used full-mouth periodontal
      assessments.

PMID- 7587149
TI  - Variability in assessment of prevalence of temporomandibular joint disorders in
      Danish adolescents.

PMID- 7587148
TI  - What is the effective concentration of fluoride?

PMID- 7587150
TI  - Tobacco habits, attitudes and participating behavior in tobacco prevention among
      dental personnel in Sweden.

PMID- 7587151
TI  - Health care reform: will the subject fall out of the topic?

PMID- 7587153
TI  - Enhancing family advocacy networks: an analysis of the roles of sponsoring
      organizations.
AB  - Family participation in shaping system reforms in children's mental health has
      increased over the past ten years. In 1990 the National Institute of Mental
      Health funded the development and enhancement of 15 statewide advocacy
      organizations that were to be controlled and staffed by families of children who
      have serious emotional disorders. These family advocacy organizations had three
      major goals: to establish support networks, to advocate for service system
      reforms, and to develop statewide family advocacy networks. Seven family advocacy
      networks worked with sponsoring organizations because they needed assistance
      and/or could not receive funding directly. State and local chapters of the
      National Alliance for the Mentally Ill and the National Mental Health Association
      served in this capacity. Because there were no guidelines to educate sponsoring
      organizations about their interorganizational roles and responsibilities, staff
      of some sponsoring organizations used approaches that were supportive and
      effective, while staff in other organizations used methods that were
      counterproductive. The information and recommendations discussed in this paper
      are based on evaluation data and observations of the relationships between seven
      sponsoring organizations and family advocacy groups over a three-year period.
      This paper proposes a conceptual framework that includes: (1) a clear definition
      of the sponsoring organization's roles, and (2) an analysis of the advantages,
      limitations, and critical issues for the sponsoring organization.

PMID- 7587154
TI  - Barriers to social network interventions with persons with severe and persistent
      mental illness: a survey of mental health case managers.
AB  - In order to empirically assess the existence, strength, and relative influence of
      barriers to social network interventions for persons with severe mental
      disability which have been cited in the literature, a survey of the knowledge and
      attitudes of social networks and social network interventions of eighty mental
      health case managers and case management supervisors was conducted. Findings
      indicate gaps in case managers' level of knowledge of social networks, with items
      based on empirical knowledge about social networks and severe mental disability
      least likely to be answered correctly. Case managers both perceive, and have
      experienced, a significant number of obstacles that affect their ability to
      develop social network interventions-system barriers (paperwork, caseload size,
      lack of case manager time, etc.), community barriers (stigma and lack of
      resources), and client/family barriers (lack of interest in social networks,
      clients having a "burnt out" network, clients not wanting to identify social
      network needs, etc.). Case managers cited few major barriers pertaining to their
      own level of knowledge, skills, or interest in, social network interventions.
      Strategies to address identified barriers are presented.

PMID- 7587155
TI  - Assessing the social networks of people with psychiatric disability from multiple
      perspectives.
AB  - The study uses a sample of 97 new members of a mutual-help organization for the
      seriously mentally ill and 97 of their significant others (61 family members and
      36 friends) to examine 1) the degree to which respondents' perceptions of dyadic
      relationships can be corroborated by network members and 2) the relationship of
      congruence of perception between respondent-network member pairs, characteristics
      of respondents' social networks and self-reported symptoms and social adjustment.
      Results showed strong variability in the degree to which respondents' perceptions
      were corroborated by network members, with a higher degree of corroboration for
      factual information such as face-to-face contact than for global aspects of
      dyadic relationships. Congruence of perception between respondents and family was
      associated with respondents' feelings of satisfaction about the quality of
      network ties and better psychological and social functioning. In contrast,
      congruence of perception between respondents and friends was related to a sense
      of involvement from ones network, but unrelated to respondents' mental health.
      The advantages of multiple perspectives data in studying the social ties of
      people with psychiatric disability are discussed.

PMID- 7587152
TI  - Sexually transmitted disease prevention services for female chronically mentally
      ill patients.
AB  - Chronically and variably impaired autonomy makes women with chronic mental
      illness particularly vulnerable to contracting sexually transmitted diseases
      (STDs) including AIDS. A lack of female controlled protective devices also adds
      to the vulnerability of these patients. In this context, the authors make
      recommendations for the design of clinically comprehensive and ethically
      justified programs to minimize the risk of mentally ill women for STDs. When
      female chronically mentally ill patients are at risk of STDs, barriers to the
      exercise of their autonomy must be identified and clinically treated. Preventive
      clinical interventions can also be usefully augmented by educational strategies
      and facilitate patients' communication and behavioral skills, particularly in
      order to enable them to abstain from unwanted sex or to make prospective male
      partners wear a condom. Outreach efforts to the male partners of female patients
      and to the homeless mentally ill may also be required. Preventive services could
      be integrated and coordinated with STD clinics, substance abuse treatment
      programs and family planning programs.

PMID- 7587156
TI  - A validity study of the St. Louis Inventory of Community Living Skills.
AB  - Clinicians who work with the long term mentally ill often need an instrument
      which measures the level of community living skills. Independent raters scored 60
      clients of the St. Louis Community Placement Program on the St. Louis Inventory
      of Community Living Skills (SLICLS), a 15-item instrument that requires little
      training and only a few minutes to complete. There was good inter-rater
      reliability and internal consistency. Construct validity was demonstrated for
      clients in three types of residences. Concurrent validity was demonstrated in
      relation to the longer Missouri Level of Care Instrument.

PMID- 7587158
TI  - Comparison between exact and parametric distributions of multiple inter-raters
      agreement coefficient.
AB  - The Global Kappa statistic can be used for measuring the degree of agreement
      between more than two raters. In this paper, we give simple computation formulas
      in the case of dichotomic and no missing responses in order to describe the exact
      distribution of Kappa for various sets defined by the number of raters, of
      different examinations and of positive responses. By programming those
      computations with the SAS software package, we were able to compare the exact and
      parametric distributions of Kappa. Although the correlation between parameters is
      high, a linear regression analysis shows that a strong imbalance between positive
      and negative responses can lead to misinterpretation of the results when using
      the parametric method.

PMID- 7587157
TI  - The economic advancement of the mentally ill in the community: 1. Economic
      opportunities.
AB  - Consumer cooperatives have been shown to be feasible in Europe for generating
      adequately reimbursed jobs for the mentally ill, and may be viable in the U.S..
      Such businesses can gain a market advantage by offering goods and services to
      mental health agencies or to the consumer group. Interviews with 50 mentally ill
      people living in Boulder, Colorado, identified sizable markets controlled by
      consumers: the average mentally ill person in the sample consumes $2,000 a month
      in psychiatric treatment, accommodation, food, medication and other goods and
      services. The findings suggest several income-generating opportunities. Consumers
      can be employed as mental health service providers, under certain conditions a
      consumer-cooperative pharmacy may be established, and some types of housing
      cooperative are viable.

PMID- 7587159
TI  - Computerized measurement of the content analysis of natural language for use in
      biomedical and neuropsychiatric research.
AB  - Over several decades, the senior author, with various colleagues, has developed
      an objective method of measuring the magnitude of commonly useful and pertinent
      neuropsychiatric and neuropsychological dimensions from the content and form
      analysis of verbal behavior and natural language. Extensive reliability and
      validation studies using this method have been published involving English,
      German, Spanish and many other languages, and which confirm that these Content
      Analysis Scales can be reliably scored cross-culturally and have construct
      validity. The validated measures include the Anxiety Scale (and six subscales),
      the Hostility Outward Scale (and two subscales), the Hostility In Scale, the
      Ambivalent Hostility Scale, the Social Alienation-Personal Disorganization Scale,
      the Cognitive Impairment Scale, the Depression Scale (and seven subscales), and
      the Hope Scale. Here, the authors report the development of artificial
      intelligence (LISP based) software that can reliably score these Content Analysis
      Scales, whose achievement facilitates the application of these measures to
      biomedical and neuropsychiatric research.

PMID- 7587160
TI  - MCML--Monte Carlo modeling of light transport in multi-layered tissues.
AB  - A Monte Carlo model of steady-state light transport in multi-layered tissues
      (MCML) has been coded in ANSI Standard C; therefore, the program can be used on
      various computers. Dynamic data allocation is used for MCML, hence the number of
      tissue layers and grid elements of the grid system can be varied by users at run
      time. The coordinates of the simulated data for each grid element in the radial
      and angular directions are optimized. Some of the MCML computational results have
      been verified with those of other theories or other investigators. The program,
      including the source code, has been in the public domain since 1992.

PMID- 7587162
TI  - Monte Carlo generation of SB and SU distributions.
AB  - Generating random variables from specific bounded or unbounded distributions is a
      problem frequently encountered in Monte Carlo studies. Of particular interest is
      that of transforming variables from a standard normal distribution to a given
      Johnson's SB or SU distribution with specified (gamma, delta) parameters. We use
      a composite standard normal generator N (0.1) to generate Johnson's SB or SU
      distributions with (gamma, delta) parameters. Goodness-of-fit tests and graphical
      illustrations demonstrate the adequacy of the empirical distributions.

PMID- 7587161
TI  - MARKOV: a computer program for multi-state Markov models with covariables.
AB  - This paper discusses a computer program, called MARKOV, designed to fit a multi
      state Markov model with covariables, with a particular emphasis on the analysis
      of survival data. The Markov model consists of k-1 transient disease states and
      one absorbing state. The exact transition times are not observed, except in
      situations such as death. Baseline transition intensities and regression
      coefficients are estimated via the method of maximum likelihood using a quasi
      Newton optimization algorithm. The program's output includes the parameter
      estimates, the standard error of the estimates, the matrix of the correlation of
      the estimates and minus two times the log-likelihood function, evaluated at the
      initial values and at the maximum likelihood estimates. Optionally, survival
      curves can be generated from each transient state, for one or more combination of
      covariable values and simple tests about the parameters. The program is
      illustrated by using a four-state model to determine factors influencing diabetic
      retinopathy in young subjects with insulin-dependent diabetes mellitus.

PMID- 7587163
TI  - A personal computer-based system for parallel line analysis of bioassay data.
AB  - A program is described for symmetric parallel line analysis of bioassay data with
      a logistic dose-response relationship. Dose-response relationship is transformed
      to semilog or log-log. A regression line can be calculated for the dose-response
      curve for standard and test samples, and produces potency estimate of test sample
      preparation relative to the standard preparation based on parallel-line bioassay
      statistical methods [3,4], together with detailed analysis of variance, estimates
      of slope, intercept and chi 2 test which permits a very sensitive test for
      linearity and parallelism of standard and test sample and facilitates detection
      of 'outliers', i.e. samples exhibiting non-parallelism. The general comparison of
      dose-response relationships produced by the program are a feature of particular
      interest.

PMID- 7587164
TI  - Evaluation on blood platelets by the image analysis system VIDAS 2.5.
AB  - This paper introduces a program written on the image analysis system VIDAS 2.5.
      It enables the automatic quantification of high numbers of adhesion areas of
      vital human platelets, thus allowing statistical analysis. These adhesion areas
      were observed by reflection contrast microscopy (RCM), which generates images of
      an intense contrast and serves as a prerequisite for an evaluation by image
      analysis. However, RCM-photographs of the observed platelets have highly varying
      mean greyvalues and greyranges. These common problems for self-operating
      identification are excluded by two procedures within the program: 1. calibration
      of the scanning process for an optimal use of the available greyvalues provided
      by the negative, camera, and the image analysis system; and 2. relation of the
      threshold for discrimination of adhesion areas to the statistic parameters of the
      histogram within each individual digitized image. Images processed according to
      these prerequisites were transferred to the VIDAS implemented routines for
      identification and measurement of areas. Thus, image analysis combined with RCM
      offers a tool for basic and clinical platelet research, which is shown by an
      example of stimulation and inhibited stimulation of platelet activation.

PMID- 7587165
TI  - User satisfaction of general practitioners with HIOS+, a medical decision support
      system.
AB  - In this article, a user satisfaction study is described. The Formal Interpreter
      (FI) and the Free-text Formalizer (FF) are modules of the medical DSS HIOS+. With
      FF, medical experts can formalize topics selected from free-text ICHPPC-II
      defined criteria into queries. FI gives decision support to GPs in their daily
      work by interpreting queries belonging to entered ICPC codes and presenting
      advice/warnings concerning the validity (correctness) of the diagnoses in patient
      cases. In the study, FI was used in field and laboratory test situations by GPs.
      User satisfaction was assessed using questionnaires consisting of an adapted
      version of the Bailey questionnaire. Answers given were analysed using Bailey's
      approach and the 'two-sample t-test'. The most important result of the FI
      evaluation was that users given active decision support were more satisfied with
      FI than users given none or only textual decision support.

PMID- 7587166
TI  - Reconstruction of complex passageways for simulations of transport phenomena:
      development of a graphical user interface for biological applications.
AB  - Flow of fluids, such as blood, lymph and air, plays a major role in the normal
      physiology of all living organisms. Within individual organ systems, flow fields
      may significantly influence the transport of solutes, including nutrients and
      chemical toxicants, to and from the confining vessel walls (epithelia and
      endothelia). Computational fluid dynamics (CFD) provides a potentially useful
      tool for biologists and toxicologists investigating solute disposition in these
      flow fields in both normal and disease states. Application of CFD is dependent
      upon generation of accurate representations of the geometry of the system of
      interest in the form of a computational reconstruction. The present
      investigations, which were based on studies of the toxicology of inhaled reactive
      gases in the respiratory tract of rodents, provide computer programs for the
      generation of finite element meshes from serial tissue cross-sections. These
      programs, which interface with a commercial finite element fluid dynamics
      simulation package (FIDAP 7.05, Fluid Dynamics International, Evanston, IL),
      permit simulation of fluid flow in the complex geometries and local solute mass
      flux to the vessel walls of biological systems. The use of these programs and
      their application to studies of respiratory tract toxicology are described.

PMID- 7587168
TI  - Circadian and ultradian rhythms of peripheral growth hormone concentrations in
      lactating dairy cows.
AB  - To investigate possible circadian and ultradian periodicities for plasma growth
      hormone in lactating dairy cows, integrated 15-min blood samples taken
      sequentially over 48 hr from six cows were analyzed by radioimmunoassay. The cows
      were housed in an environmental chamber at 19 +/- 0.5 degree C, 50% relative
      humidity, and 16 hr of light and 8 hr of darkness (lights on at 0700 hr); fed
      daily at 0900 hr; and milked at 0800 and 2000 hr. Peripheral concentrations of
      growth hormone for all six cows exhibited sinusoidal circadian rhythms with
      average minima of 4.1 ng/ml at 1820 hr and maxima of 5.3 ng/ml at 0630 hr.
      Estimated periods of ultradian rhythms for individual cows by spectral analysis,
      peak identification, and fitting cosine functions using least squares were 71 to
      83 min for all cows. No direct relationship between ultradian peaks and milking
      or feeding was apparent. In conclusion, a circadian rhythm and an ultradian
      rhythm with a period around 80 min are probably intrinsic to mechanisms
      regulating peripheral growth hormone concentrations in the lactating dairy cow.

PMID- 7587167
TI  - The ovarian insulin and insulin-like growth factor system with an emphasis on
      domestic animals.
AB  - Insulin and insulin-like growth factors (IGFs) have direct effects on cultured
      ovarian cells. These effects include stimulation of granulosa cell mitogenesis,
      granulosa and luteal cell progesterone production, and thecal cell androgen
      production and appear similar among species. However, species differences exist
      with regard to insulin and IGF-I effects on granulosa cell estradiol production.
      In addition to endocrine effects of insulin and IGFs, IGFs are produced by
      granulosa, thecal, and luteal cells, allowing for an intraovarian autocrine and
      paracrine system. Granulosa, thecal, and luteal cells contain receptors for
      insulin and IGFs, and these receptors appear to mediate the effects of insulin
      and IGFs. Adding to the complexity of the regulatory role of IGFs is the presence
      of IGF-binding proteins (IGFBPs) within the ovary. These IGFBPs are produced by
      granulosa, thecal, and luteal cells, and their production is hormonally
      regulated. Evidence for a coherent mechanism by which insulin, IGFs, and IGFBPs
      interact and regulate ovarian function in vivo has yet to be found.

PMID- 7587169
TI  - Changes in plasma luteinizing hormone concentration in turkey hens after
      switching from short-day to long-day photoperiods.
AB  - Luteinizing hormone (LH) has been reported to increase in plasma shortly after
      switching photosensitive turkey hens from short-day (SD) photoperiods (6 hr
      light:18 hr dark) to long-day (LD) photoperiods (14 hr light: 10 hr dark). An
      experiment was conducted to determine the timing and nature of these changes in
      plasma LH concentrations after the photostimulation of photosensitive turkey
      hens. The turkey hens were cannulated (jugular vein) to allow serial bleeding
      every 15 min for 48 hr. One group (controls) was continued under the SD
      photoperiod, and one group (treated) was switched to the LD photoperiod by the
      addition of 8 hr of light to the end of the photoperiod. In the control hens, no
      changes were seen in the observed or calculated baseline concentrations of LH or
      in the frequency and amplitude of LH peaks during the 48 hr of serial bleeding.
      In the treated hens, the observed and baseline concentrations of LH increased
      during the first LD scotoperiod, with a further increase during the second LD
      scotoperiod. This rapid increase was due to an increase in the baseline LH
      concentration, whereas no consistent changes were detected in the frequency and
      amplitude of LH peaks.

PMID- 7587170
TI  - Characterization and distribution of epidermal growth factor receptors in the
      skin and wool follicles of the sheep fetus during development.
AB  - We have determined the binding affinity and capacity and relative distribution of
      epidermal growth factor (EGF) receptors in the skin of the Merino sheep fetus
      before and during the development of the wool follicle population.
      Autoradiography of tissue sections incubated with [125I]EGF revealed that label
      was confined predominantly to the epidermis and dermoepidermal junction before
      follicle formation, at 30 and 55 d of gestation. During follicle initiation (Days
      60 to 65), receptor activity was distributed over the epidermis, including the
      epidermal aggregations of primordia at the dermoepidermal junction. However,
      receptor concentrations, as revealed by grain counts of autoradiographs, were
      reduced in these regions when compared with 55-d skin. The receptor distribution
      over the epidermis and its derivatives did not alter during subsequent follicle
      development, although the intensity of labeling increased as the follicles
      matured. Specific receptor binding was not observed above background levels in
      the dermis and dermal papillae during all stages of follicle development. At
      follicle maturation, EGF receptors were widely distributed over the cells of the
      epidermis and the epidermal derivatives of the cutaneous appendages but were
      particularly localized in the sebaceous glands and outer root sheath (see also
      Wynn et al. 1989). EGF immunoreactive material has also been found at these sites
      (du Cros et al. 1992), suggesting an autocrine role for EGF in the regulation of
      cell function. It is likely that the differentiation-promoting activities of EGF
      may predominate over those of growth, because the receptor-bearing cells were not
      members of rapidly proliferating populations.

PMID- 7587171
TI  - Regulation of adrenocorticotropin secretion in vitro by anterior pituitary
      corticotrophs from fallow deer (Dama dama).
AB  - The actions of corticotropin-releasing hormone (CRH), vasopressin (VP), the
      synthetic glucocorticoid dexamethasone (DEX), and mifepristone (RU 486), a
      glucocorticoid antagonist, on the secretion of adrenocorticotropin (ACTH) by
      cultured fallow deer corticotrophs were studied in vitro. On Day 5 of primary
      culture, corticotrophs were challenged for up to 4 hr with medium alone
      (Control), CRH, VP, DEX, forskolin (FSK), phorbol ester (TPA), cyclic AMP (cAMP),
      and/or RU 486 at various concentrations and combinations. CRH, VP, FSK and TPA
      each stimulated (P < 0.01) the secretion of ACTH in dose- and time-related
      manners. Relative to Control, CRH at 0.001 and 0.1 microM and VP at 0.01 and 1
      microM increased (P < 0.01) medium concentration of ACTH by 7.3-, 13.5-, 3.7- and
      9.0-fold, respectively. There was a treatment x incubation time interaction (P <
      0.01) such that at 30-min posttreatment, CRH-induced ACTH secretion tended (P <
      0.10) to be less than that obtained via VP treatment, whereas at 1, 3, and 4 hr
      posttreatment, medium concentration of ACTH from cells treated with 0.1 microM
      CRH was greater (P < 0.05) than that in cells treated with 1 microM VP. At
      equimolar doses of 0.01 and 0.1 microM, CRH was 3.4- and 3.0-fold more potent
      (treatment x dose, P < 0.05) than VP. Cotreatment with 1 microM DEX reduced (P <
      0.001) the stimulatory effects of CRH (0.1 microM), VP (1 microM), FSK (10
      microMs), TPA (0.1 microM), and cAMP (0.001 M). However, the coaddition of RU 486
      (1 microM) to the CRH plus DEX- and the FSK plus DEX-treated wells partially
      negated the inhibitory effects of DEX. RU 486 completely negated the inhibitory
      effects of DEX on the VP-, TPA-, and cAMP-stimulated secretion of ACTH. These
      data indicate that CRH is a more potent stimulator of ACTH secretion than is VP
      in primary culture of fallow deer pituitary cells. This study also demonstrates
      the utility of an in vitro culture system to investigate stress-related hormonal
      interactions in cervids.

PMID- 7587172
TI  - Effect of dietary energy intake and exogenous porcine growth hormone
      administration on circulating porcine growth hormone concentration and response
      to human growth hormone-releasing factor administration in growing swine.
AB  - In a 2 x 2 treatment array (n = 4 pigs/treatment), the effects of feed intake (ad
      libitum vs. restricted to 60% ad libitum) and the daily administration of
      excipient buffer or porcine pituitary-derived growth hormone (GH) at a dose of
      100 micrograms/kg body weight per day on serum GH profile and human growth
      hormone-releasing factor (hGRF) response were examined in barrows weighing 55 kg.
      Feed intake treatment was implemented from 25 to 55 kg live weight. Buffer or GH
      treatment was implemented for 10 d before sampling. After GH treatment, the
      integrated serum GH concentration area was 25% greater in barrows fed
      restrictively. Data are consistent with the suggestion that GH dose to improve
      the efficiency of lean tissue deposition be adjusted according to feeding
      regimen. The serum GH response to hGRF was also altered by level of feed intake.
      The ad libitum feeding of buffer-treated animals resulted in a monophasic serum
      GH response to hGRF, whereas barrows fed restrictively had a biphasic response to
      hGRF. Together, these data suggest that feed intake pattern alters GH secretion
      and as such could influence the practical implementation of somatotropin as a
      metabolism modifier in swine.

PMID- 7587174
TI  - Severe hepatocellular disease as an unusual presentation of metastatic melanoma.
AB  - Melanoma is a cutaneous malignancy with an incidence that is rising. Surgery is
      curative if performed prior to metastasis. Liver metastasis is common and is
      often associated with an elevation in lactic dehydrogenase. A rise in
      transaminases is unusual; typically it is low in these patients. We describe a
      case of metastatic melanoma which presented as severe hepatocellular disease.

PMID- 7587175
TI  - Telemedicine: delivering medical expertise across the state and around the world.
AB  - Many aspects of medical care can now be delivered at a distance using
      telemedicine technology. Rapid video and computer-based communication of medical
      information makes it possible for a physician to "examine" a patient located in
      another city, to view highly detailed medical images, to consult with distant
      subspecialists, or to supervise complex medical procedures. This same technology
      can bring scattered health-care workers together for joint teaching conferences.
      The Yale Telemedicine Center has initiated a number of such programs ranging from
      providing consultations in real time to physicians in Saudi Arabia, to
      interpreting medical images across town or across the state. Telemedicine will
      become a powerful tool for managed health-care organizations which are
      responsible for the medical needs of widely distributed patients in a vertically
      integrated health-care delivery system. This paper reviews the evolution of
      telemedicine, its technical fundamentals, specific medical applications, and the
      activities of the Yale Telemedicine Center. Evolving uses for telemedicine in
      Connecticut are described.

PMID- 7587173
TI  - Free radicals, oxidative stress, oxidized low density lipoprotein (LDL), and the
      heart: antioxidants and other strategies to limit cardiovascular damage.
AB  - The heart is the most susceptible of all the organs to premature aging and free
      radical oxidative stress. Clinical research has clearly documented the role of
      free radical damage and the progression of numerous degenerative diseases,
      particularly cardiovascular disease. This may be the result of acute ischemia
      reperfusion injury, endothelial damage of hyperhomocysteinemia, as well as
      chronic oxidative damage secondary to lipid peroxidation. Fortunately, although
      highly responsive, and therefore vulnerable to the effects of oxidative stress,
      the heart is also receptive to the benefits of targeted phytonutrients,
      antioxidants, and nutritionals. The effects of antioxidant nutrients have been
      extensively evaluated in epidemiological, population, and clinical studies.
      Phytonutrients such as the natural flavonoids and carotenoids found in fresh
      fruits and vegetables or vitamins C, E, and beta-carotene have powerful
      antioxidant effects. In addition, minerals like selenium and nutrients such as
      coenzyme Q10 will minimize free radical risk and optimize a favorable outcome
      from the ubiquitous presence of oxidative stress on the cardiovascular system.
      The B complex, particularly folic acid, B12, and B6 are also essential in the
      prevention of hyperhomocysteinemia, another major risk factor for the circulatory
      system. Measures to minimize accumulation of heavy metals in the body, especially
      iron and copper, which are capable of initiating adverse free radical reactions,
      will also help to assuage oxidative stress. Thus, the combination of a healthy
      diet supplemented with antioxidants and phytonutrients may be useful in the
      prevention and promotion of optimum cardiovascular health.

PMID- 7587177
TI  - Consent for release of confidential disciplinary records.

PMID- 7587176
TI  - Financing of graduate medical education.

PMID- 7587178
TI  - Conversion of CMIC under serious consideration.

PMID- 7587179
TI  - Severe hypothermia in the elderly.
AB  - Hypothermia is not an uncommon clinical problem in the geriatric population.
      Several factors place elderly individuals at risk, including their reduced
      ability to sense and react to cold and their underlying medical conditions and
      medications. Successful detection and treatment of these patients involve an
      awareness of these risk factors and the characteristic physiology of the elderly,
      as well as an appreciation of the often controversial aspects of hypothermia
      management. Elderly victims of severe hypothermia have a particularly grave
      prognosis. We present one of the oldest reported survivors of severe hypothermia,
      and discuss some unique aspects of his presentation.

PMID- 7587182
TI  - Drugs for hypertension.

PMID- 7587183
TI  - Medicare must be reformed.

PMID- 7587180
TI  - Alcoholic rhabdomyolysis: a review.
AB  - Two episodes of acute alcoholic myopathy occurring in one patient are reported to
      focus attention on a common problem, albeit one not well recognized. A brief
      review of rhabdomyolysis and its complications is presented.

PMID- 7587181
TI  - Management of difficult wounds with Biobrane.
AB  - Nine patients with open wounds are reviewed. All wounds were debrided prior to
      application of Biobrane. Silver sulfadiazine was applied twice daily. All healed
      uneventfully after closure. Biobrane is recommended for treatment of difficult
      and large open wounds; its use reduces evaporative loss and bacterial
      proliferation, enabling development of a healthy wound base suitable for grafting
      or delayed closure. This approach can prevent the necessity for flap repair and
      reduce pain during wound dressing. Wounds such as lower extremity ulcers are
      often resistant to therapy. Repeated debridements may result in further
      desiccation without progression of wound healing. Biobrane-treated wounds develop
      a healthy granulating base which can be grafted or closed.

PMID- 7587184
TI  - Compliance and oral contraceptives: a review.
AB  - Compliance difficulties are more common among oral contraceptive (OC) users than
      generally appreciated by clinicians, in part because unintended pregnancy is a
      relatively infrequent consequence and in part because more common manifestations
      such as spotting and bleeding may not be recognized as resulting from poor
      compliance. While improving compliance is a shared responsibility of patients,
      clinicians, and manufacturers, the clinician is the focal point for these
      efforts. Counseling must be individualized, which requires knowledge of factors
      that predict compliance and an understanding of the patient's decision-making
      process as it relates to medications. Most OC compliance research has focused on
      adolescents, where predictors of poor compliance include multiple sex partners,
      low evaluation of personal health, degree of concern about pregnancy, and
      previous abortion. Good compliance has been linked with patient satisfaction with
      the clinician, the absence of certain side effects, establishing a regular daily
      routine to take OCs, and reading information distributed with OC packaging.

PMID- 7587186
TI  - Effect of low-dose oral triphasic contraceptives on blood viscosity, coagulation
      and lipid metabolism.
AB  - The purpose of the study was to determine the relationship between
      hemorheological profile, i.e. blood viscosity, and other risk factors for
      cardiovascular and thrombotic diseases in women taking oral contraceptives and if
      blood viscosity may be considered a marker of cardiovascular risk in OC users.
      Plasma levels of coagulation parameters, serum lipids, blood viscosity and RBC
      deformability were determined in a group of 10 women taking OC vs. 10 controls.
      The blood parameters were evaluated before OC use and thereafter at 3 and 6
      months. A significant change in the partial thromboplastin time, fibrinogen, HDL
      and apolipoprotein A-I was observed, while the other parameters remained
      unchanged. Plasma viscosity was significantly increased during OC treatment;
      whole blood viscosity and RBC deformability remained unchanged. However, although
      some parameters were significantly modified during OC treatment, all alterations
      remained within the normal range of laboratory values. The data confirm that low
      dose triphasic OC therapy does not affect significantly the coagulation system,
      serum lipid metabolism and blood viscosity. Plasma viscosity measurement may be
      considered as a marker for monitoring women using OC because it is apparently the
      most sensitive parameter.

PMID- 7587187
TI  - Characteristics and experiences of American women electing for early removal of
      contraceptive implants.
AB  - The study describes the experiences of 430 women who had Norplant(R)
      contraceptive implants removed prior to the five years of method effectiveness.
      Each subject was surveyed when the implants were inserted and again at the time
      of removal. Descriptive data are presented concerning perceptions of the method
      before insertion and after removal, reactions to the contraceptive and
      experiences associated with the removal procedure. Subjects' use of Norplant
      implants ranged from 14 days to 40 months, with a mean of 13.3 and median of 13
      months. Over 95% reported changes in menstrual bleeding patterns and 95%
      experienced other non-bleeding related side effects. Non-bleeding side effects
      were the most frequently indicated reasons for removal, followed by bleeding
      changes. The mean removal time was 34 minutes with a median of 25 minutes. Over
      48% reported experiencing significant pain during the removal procedure, and 27%
      stated that the pain was greater than expected. Despite electing for early
      removal of implants,the majority of women surveyed indicated satisfaction with
      all aspects of the method save its effect on their overall health. Although
      method-related side effects were intolerable for most subjects, their overall
      perception of the method was generally satisfactory.

PMID- 7587185
TI  - Relationships between blood pressure, oral contraceptive use and metabolic risk
      markers for cardiovascular disease.
AB  - Data from a previous study, designed to compare metabolic risk markers for
      cardiovascular disease in non-users and oral contraceptive (OC) users, were
      analysed to evaluate the influence of OC composition on blood pressure. Healthy,
      female volunteers (1189 women) either not using OC (non-users) or currently using
      one of six different combined formulations (users) were compared. Combinations
      studied contained 30-40 micrograms ethinyl estradiol combined with the progestins
      levonorgestrel, norethindrone (at two and three different doses, respectively) or
      desogestrel. After statistical standardisation to account for the significantly
      greater age of the non-users and longer duration of OC use amongst the
      levonorgestrel combination users, mean blood pressure was higher, compared with
      non-users, in users of monophasic or triphasic levonorgestrel combinations
      (systolic: +4.3 mmHg (p < 0.001) and +2.7 mmHg (p < 0.001), respectively;
      diastolic: +2.6 mmHg (p < 0.001) and +2.3 mmHg (p < 0.05), respectively). Blood
      pressures in users of monophasic norethindrone and desogestrel combinations were
      not significantly raised and there was no increase in the proportion of women
      with abnormal values. Diastolic and systolic blood pressures were positively
      associated with oral glucose tolerance test insulin response (r = 0.11 (p < 0.01)
      and r = 0.15 (p < 0.001), respectively) in users but not in non-users. Currently
      used OC containing norethindrone or desogestrel progestins have little impact on
      blood pressure. Their correlated reduction in impact on insulin concentrations,
      though small, suggests common mechanisms through which OC affect blood pressure
      and insulin.

PMID- 7587189
TI  - The influence of the Gyne-T 380S IUD on menstrual blood loss and iron status.
AB  - The influence of the Gyne-T 380S intrauterine contraceptive device (IUD) on
      menstrual blood loss (MBL) and iron status (hemoglobin, hematocrit, red cell
      count and indices, and serum ferritin) was evaluated. MBL was determined
      objectively by the alkaline hematin method in 18 women (mean age 37.1 +/- 1.6 yr,
      range 22-46 yr) before and 3, 6 and 12 months after insertion of a Gyne-T 380S
      IUD. MBL prior to IUD insertion was 59 +/- 8 ml and increased to 91 +/- 11 ml (p
      < 0.01) 3 months after insertion. MBL then remained largely unchanged during the
      remainder of the observation period (6 months, 94 +/- 12 ml; 12 months, 92 +/- 13
      ml). The percentage increase in MBL at the respective measurement points ranged
      between 54 and 59% which is comparable with previous reports regarding the
      increase in MBL associated with the use of a copper IUD. There were no
      significant changes recorded in iron status parameters during the 12-month
      observation period following IUD insertion. Based on the results of the present
      study, women from developed countries apparently tolerate an increased MBL of
      approximately 55% without developing iron deficiency anemia. Iron stores were
      unchanged indicating an adequate adaptive increase in intestinal iron absorption.

PMID- 7587188
TI  - Lea's Shield: a phase I postcoital study of a new contraceptive barrier device.
AB  - Lea's Shield is a new vaginal barrier contraceptive that may offer advantages
      over existing methods. It is made of silicone which is resistant to petroleum
      based lubricants, does not absorb odors, and does not cause allergic reactions in
      users with latex sensitivity. It has an anterior loop for ease of insertion and
      removal and a one-way flutter valve. Its novel design has sufficient volume to
      fill the posterior fornix, which helps keep it in place and prevent sperm from
      entering the cervical os. This study evaluated with a standard postcoital test
      (PCT) the ability of the Lea's Shield used with spermicide or non-spermicidal
      lubricant to prevent sperm from entering midcycle cervical mucus. Ten sterilized
      women underwent four PCT cycles: one cycle in which no contraceptive barrier was
      used (a baseline cycle) and 3 cycles in which one of the following was used:
      Lea's Shield with spermicide, or with non-spermicidal lubricant, or the
      contraceptive diaphragm used with spermicide. All volunteers demonstrated more
      than 5 progressively motile sperm per high power field in the cervical mucus
      after intercourse in the baseline cycle. No motile sperm were found in the
      cervical mucus in any cycle in which Lea's Shield or the diaphragm was used with
      spermicide. No motile sperm were found in cervical mucus in 9 of 10 cycles in
      which Lea's Shield was used without spermicide. Only two progressively motile
      sperm were present in the cervical mucus of one volunteer who used the shield
      with non-spermicidal lubricant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587191
TI  - Reversibility of antigestagenic action of antiprogestin onapristone by exogenous
      progestagens during early pregnancy in guinea pig.
AB  - Ability of progesterone, gestodene, promegestone and cyproterone acetate (CPA) to
      reverse antigestagenic action of onapristone in adult female guinea pigs was
      investigated. Onapristone (10 mg/kg, s.c.) administered on post-conception days 8
      11 caused resorption of implantations and vaginal bleeding in all animals.
      Simultaneous administration of progesterone, gestodene or promegestone on days 7
      13 successfully reversed antigestagenic action of this antiprogestin, since most
      animals supplemented with these progestagens had viable implantations at autopsy
      on day 14. CPA was, however, ineffective and animals supplemented with it had
      only resorbed implantations and blood in uterus and vagina like that in
      onapristone per se treated animals. High plasma progesterone and low PGFM
      concentration were generally observed in all pregnant animals bearing viable
      implantations. PGFM (13, 14-dihydro-15-keto PGF2 alpha) was significantly
      elevated by day 14 in onapristone-treated (Group II) and CPA-supplemented (Group
      X) animals. No discernible effect on pregnancy or post-implantation embryonic
      development was observed in animals treated per se with these progestagens.

PMID- 7587190
TI  - Adolescent contraceptive use and its determinants in Bangladesh: evidence from
      Bangladesh Fertility Survey 1989.
AB  - This study is concerned with contraceptive use among the currently married
      adolescents in Bangladesh utilizing the 1989 Bangladesh Fertility Survey (BFS)
      data. The study analyzes the factors affecting the current use of contraception
      among the adolescents through bivariate and multivariate logistic regression
      analysis. The results indicate that although adolescents have almost universal
      knowledge about contraceptive methods, only 15 percent are currently using any
      method of contraception. The corresponding figures for the adults and for the
      nation as a whole are 34.4 percent and 31.4 percent, respectively. Among the
      individual methods currently used by the adolescents, the pill appears as the
      most popular method, followed by safe period. A substantial proportion of the
      adolescents were found to rely on the traditional methods of contraception. Among
      the socio-economic variables (as revealed by the logistic regression analysis),
      respondents' education, participation in the family planning decision, visit by
      family planning workers, region of residence, husband's occupation and possession
      of electricity in the household appear as the most significant factors
      determining the current use of contraception among the adolescents.

PMID- 7587193
TI  - Studies on the post-coital contraceptive mechanisms of crude extract of Sri
      Lankan marine red algae, Gelidiella acerosa.
AB  - This study investigates the potential post-coital contraceptive mechanisms of the
      crude extract of Sri Lankan marine red algae, Gelidiella acerosa, using rats. The
      dose used was 1000 mg/kg/day and the route of administration was oral. The
      results showed that the crude extract possessed potent post-coital contraceptive
      activity when administered on days 7-8 of pregnancy indicating the presence of a
      narrow window in its action. The post-coital contraceptive activity was due to an
      elevated post-implantation loss (by 89%) resulting from fetal death between days
      9-14 of pregnancy. The extract was neither estrogenic nor anti-estrogenic nor
      stressor but appeared to be anti-progestational (reduced ovarian progesterone
      output). It is suggested that the crude extract may reduce the ovarian
      progesterone release possibly via anti-platelet and PGE2-depressing activity.

PMID- 7587192
TI  - Estrogenic and antiestrogenic activities of anordiol: a comparison of uterine and
      vaginal responses with those of clomiphene citrate.
AB  - Anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta
      diol) has been variously characterized as an estrogen and as an antiestrogen. To
      more completely understand the pharmacological properties of this contraceptive
      steroid, simultaneous responses were studied in uterine, vaginal, and hepatic
      tissues. Rats received 4 daily sc injections with either anordiol, clomiphene
      citrate (CC), or the vehicle alone (C+) starting on the first day of
      pseudopregnancy. Uteri were traumatized on day 4 of pseudopregnancy, and rats
      were sacrificed 5 days later. A pseudopregnant group without uterine trauma
      served as a negative control (C-). Mean uterine weights per animal and cytosolic
      estrogen (EcR) and progesterone (PcR) receptor activities per g of DNA were all 5
      to 7-fold greater in the C+ group than in the other groups (all p < 0.05).
      However, anordiol and CC suppressed uterine weight without suppressing the
      stromal proliferative response; the DNA content of the uteri of anordiol- and CC
      treated rats was similar to that of C+ rats. Vaginal tissue exhibited estrogenic
      responses to anordiol and CC with an increase in epithelial stratification
      compared to the C+ and C- groups even though no difference in levels of EcR/g of
      DNA were expressed 5 days after the last antiestrogen dose. Binding affinities
      and serum E2 and progesterone (P) concentrations were not statistically different
      among the groups. In conclusion, anordiol produced responses in the uterus and
      vagina of the pseudopregnant rat which were indistinguishable from those of CC,
      and, therefore, we conclude that anordiol acts on these tissues as an
      antiestrogen.

PMID- 7587195
TI  - Complications of cyclosporin therapy.

PMID- 7587194
TI  - Current concepts of pathogenesis of nephrotic syndrome.

PMID- 7587197
TI  - Use of cyclosporin in the treatment of idiopathic nephrotic syndrome in adults.

PMID- 7587196
TI  - Long-term cyclosporin in steroid-dependent nephrotic syndrome.

PMID- 7587198
TI  - Use of cyclosporin in membranous and mesangioproliferative (IgA) nephropathy.

PMID- 7587199
TI  - Use of cyclosporin in lupus nephritis.

PMID- 7587201
TI  - Cyclosporin in steroid-resistant idiopathic nephrotic syndrome.

PMID- 7587200
TI  - Cyclosporin and the glomerular filtration barrier in minimal change disease and
      membranous glomerulopathy.

PMID- 7587202
TI  - Serial renal biopsies in children with idiopathic nephrosis receiving
      cyclosporin.

PMID- 7587203
TI  - Morphologic features of cyclosporin nephrotoxicity.

PMID- 7587204
TI  - David Byar: an accidental career. Scientific workshop, November 7-8, 1991,
      Bethesda, Maryland. Proceedings.

PMID- 7587205
TI  - David Byar: an accidental career.

PMID- 7587206
TI  - Dave Byar as a student.

PMID- 7587208
TI  - David Byar as a collaborator.

PMID- 7587209
TI  - David Byar as a teacher.

PMID- 7587210
TI  - Workshop on "David Byar: an accidental career"--edited composite of floor
      discussions following presentations by S. Greenhouse, M. Schneiderman, N. Mantel,
      and S. Piantadosi.

PMID- 7587207
TI  - David Byar as a supervisee.

PMID- 7587211
TI  - Some of David Byar's work: in appreciation.
AB  - David Byar wrote and thought with great clarity about randomized clinical trials
      (RCTs), pointing to their strengths--and to the limitations of alternative
      investigative approaches. An issue that he treated quite briefly in the seven
      publications that I review here is the possible gains to be had from post hoc
      covariate adjustment of RCT results. Calculations that I offer suggest that for
      realistic sample sizes and covariates of modest strength, those gains cannot be
      large, on average. The price to be paid for them is to replace the clear, cogent
      RCT paradigm with a more complex and diffuse one; this seems just cause for
      unease.

PMID- 7587212
TI  - Dave Byar's contribution to epidemiology.
AB  - Some of Dave Byar's personal qualities and his scientific approach are described.
      His work on substantive epidemiologic projects is mentioned briefly. There
      follows a review of his work on theoretical issues, including extentions of the
      Mantel-Haenszel procedure and other contingency table methods, confounding, and
      estimation of attributable and absolute risk from case-control data.

PMID- 7587213
TI  - On the role, design, and analysis of disease prevention trials.
AB  - Some differences between prevention and therapeutic trials are reviewed, as are
      some of David Byar's contributions to the methodology and practice of prevention
      trials. This leads to a more detailed discussion of three more technical topics
      pertinent to prevention trials: (i) the role that aggregate data studies may be
      able to play to complement analytic epidemiologic studies and prevention trials
      in the identification of disease prevention strategies; (ii) the methods for
      analysis of correlated response data, as may arise in group randomized trials;
      and (iii) the importance of emphasizing overall benefits vs. risks in the design
      and conduct of disease prevention trials.

PMID- 7587214
TI  - David Byar's approach to the analysis of survival data with covariates.
AB  - The analysis of censored survival data with covariates was central to most of
      David Byar's research in cancer epidemiology and clinical trials. His general
      approach is outlined briefly, with particular reference to the construction of
      risk groups. Other topics include the choice between fully and semiparametric
      models, and the interpretation of interactions.

PMID- 7587215
TI  - In memoriam: David Byar as an AIDS activist.

PMID- 7587216
TI  - The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. Introduction.

PMID- 7587218
TI  - Rationale, design, and conduct of the PEPI Trial. Postmenopausal
      Estrogen/Progestin Interventions.
AB  - There is growing and consistent evidence that estrogen use in postmenopausal
      women is associated with a substantial reduction in the occurrence of
      cardiovascular disease. However, remarkably little is known about the biological
      mechanisms by which estrogen therapy may influence risk. Even less information is
      available on the cardiovascular effects of combined estrogen-progestin use. PEPI
      was not designed to test whether estrogen and estrogen-progestin therapy is
      efficacious in the prevention of cardiovascular disease, as a much larger trial
      with clinical disease outcomes is needed to answer that question. However, PEPI
      will provide critical evidence regarding the potential effectiveness of the
      various estrogen and estrogen/progestin regimens ni altering risk factors for
      cardiovascular disease in women. Detailed information on factors such as
      adherence, side effects, and general patient acceptability will also be
      ascertained. The main results from PEPI will provide the scientific community
      with information on the basic actions of estrogen and estrogen/progestin therapy
      on four biological systems believed to be causally associated with cardiovascular
      disease occurrence. Further, since the trial is designed to continue for 3 years,
      PEPI will be able to provide information on longer term as well as short-term
      effects on these systems. Finally, the results from PEPI should enable women and
      their physicians to select an optimal hormonal regimen, i.e., one that is
      acceptable, safe, and provides the most beneficial and least deleterious changes
      in cardiovascular and other risk factors.

PMID- 7587217
TI  - Recruitment of postmenopausal women in the PEPI Trial. Postmenopausal
      Estrogen/Progestin Interventions.

PMID- 7587220
TI  - Baseline characteristics of the PEPI participants. Postmenopausal
      Estrogen/Progestin Interventions.

PMID- 7587222
TI  - Measurements of medicine.

PMID- 7587219
TI  - Physical and laboratory measurements in the PEPI Trial Postmenopausal
      Estrogen/Progestin Interventions.

PMID- 7587223
TI  - Life measures before and one year after admission to an intensive care unit.

PMID- 7587221
TI  - Biophysical parameters affecting osteoporosis.

PMID- 7587224
TI  - Nitric oxide inhibition in the treatment of septic shock.

PMID- 7587226
TI  - Physiologic monitoring devices.

PMID- 7587225
TI  - Cerebral near-infrared spectroscopy: ready for prime time?

PMID- 7587227
TI  - Establishing the relative accuracy of three new definitions of the adult
      respiratory distress syndrome.
AB  - OBJECTIVES: Over the last few years, new definitions of the adult respiratory
      distress syndrome (ARDS) have been introduced that potentially identify patients
      earlier in their course of acute lung injury. However, these definitions have
      never been compared with any of the older and potentially stricter definitions of
      ARDS to determine if similar patients are eventually identified. We compared new
      definitions of ARDS--as represented by the Lung Injury Score, a modified Lung
      Injury Score, and the American-European Consensus Conference definition--against
      a stricter definition of ARDS to determine their accuracy. DESIGN: Prospective.
      SETTING: Intensive care unit (ICU) patients in a tertiary, university-affiliated
      city hospital. PATIENTS: ICU patients with clearly defined at-risk diagnoses for
      ARDS (group 1, n = 111) and general medical ICU patients without clearly defined
      at-risk diagnoses for ARDS (group 2, n = 125). MEASUREMENTS AND MAIN RESULTS:
      Measurements of hypoxemia, static respiratory system compliance, positive end
      expiratory pressure, radiographic changes, and general demographic information
      were collected. The sensitivity, specificity, positive-predictive value, negative
      predictive value, and accuracy of all three new definitions were determined.
      Accuracy was defined as the true-positive plus the true-negative results divided
      by the total number of patients. When compared with a stricter definition of
      ARDS, all three definitions maintained a high degree of accuracy in those
      patients with a clearly defined at-risk diagnosis (group 1): Lung Injury Score
      90.0% (95% confidence interval 84-96); modified Lung Injury Score 97.3% (95%
      confidence interval 94-100), and the American-European Consensus Conference
      definition 97.3% (95% confidence interval 94-100). For these at-risk patients,
      the accuracy of the modified Lung Injury Score and the American-European
      Consensus Conference definition was significantly better than the Lung Injury
      Score when compared with the strict definition (p = .027 for both comparisons).
      Although all three definitions maintained an accuracy of > 90% for general
      medical ICU patients (group 2), the low frequency of ARDS in these patients
      (3.4%) produced a low positive-predictive value for all three definitions.
      CONCLUSIONS: We conclude that the Lung Injury Score, the modified Lung Injury
      Score, and the American-European Consensus Conference definition identify similar
      patients, provided that these methods are applied to patients with clearly
      defined at-risk diagnoses for ARDS.

PMID- 7587229
TI  - Quality of life measures before and one year after admission to an intensive care
      unit.
AB  - OBJECTIVE: To assess outcome of patients admitted to an intensive care unit
      (ICU), using a prospective 1-yr follow-up, with special emphasis on various
      quality of life measures before and after admission to the ICU. DESIGN:
      Prospective comparison of quality of life before and 1 yr after admission to the
      ICU. SETTING: Eleven-bed adult medical/surgical ICU. PATIENTS: All patients
      admitted to the ICU over a 1-yr period were eligible for inclusion in this study.
      Repeat admissions were enrolled only on first admission. Patients < 17 yrs of age
      and those patients who died within 24 hrs of admission were excluded.
      INTERVENTIONS: Quality of life measures were collected before and 6 and 12 months
      after ICU admission. MEASUREMENTS AND MAIN RESULTS: The following data were
      collected: duration of ICU and hospital stay; ICU, hospital, 6- and 12-month
      mortality; quality of life (level of activity, activities of daily living,
      perceived health, support, and outlook on life) and place of residence at
      baseline and 12 months after ICU admission. There were 504 patients who met the
      study criteria; age 55 +/- 20 yrs (median 59), 229 female and 275 male. Mean ICU
      length of stay was 4.3 +/- 7.4 days. Hospital length of stay was 31 +/- 41 days.
      Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 14 +/- 7.
      Cumulative mortality: ICU 5.4%, hospital 13.5%, 6 month 20.6%, and 12 month 25%.
      One year quality of life questionnaires were completed for 293 patients. Relative
      to baseline, there was a decrease in the level of activity and activities of
      daily living at 12 months (p < .01). Perceived health status increased over the
      year for patients > or = 75 yrs of age (p < .01). There was no difference in the
      level of support from family or friends, or outlook on life, at 12 months. At 1
      yr, 262 (89%) patients were living at home. CONCLUSION: Patients admitted to
      intensive care tend to have a decrease in the level of activity and activities of
      daily living 1 yr after their ICU stay, although in the very elderly, perceived
      health status increases. As well, the majority (89%) of patients return home.

PMID- 7587228
TI  - Multiple organ dysfunction score: a reliable descriptor of a complex clinical
      outcome.
AB  - OBJECTIVE: To develop an objective scale to measure the severity of the multiple
      organ dysfunction syndrome as an outcome in critical illness. DESIGN: Systematic
      literature review; prospective cohort study. SETTING: Surgical intensive care
      unit (ICU) of a tertiary-level teaching hospital. PATIENTS: All patients (n =
      692) admitted for > 24 hrs between May 1988 and March 1990. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Computerized database review of MEDLINE identified
      clinical studies of multiple organ failure that were published between 1969 and
      1993. Variables from these studies were evaluated for construct and content
      validity to identify optimal descriptors of organ dysfunction. Clinical and
      laboratory data were collected daily to evaluate the performance of these
      variables individually and in aggregate as an organ dysfunction score. Seven
      systems defined the multiple organ dysfunction syndrome in more than half of the
      30 published reports reviewed. Descriptors meeting criteria for construct and
      content validity could be identified for five of these seven systems: a) the
      respiratory system (Po2/FIO2 ratio); b) the renal system (serum creatinine
      concentration); c) the hepatic system (serum bilirubin concentration); d) the
      hematologic system (platelet count); and e) the central nervous system (Glasgow
      Coma Scale). In the absence of an adequate descriptor of cardiovascular
      dysfunction, we developed a new variable, the pressure-adjusted heart rate, which
      is calculated as the product of the heart rate and the ratio of central venous
      pressure to mean arterial pressure. These candidate descriptors of organ
      dysfunction were then evaluated for criterion validity (ICU mortality rate) using
      the clinical database. From the first half of the database (the development set),
      intervals for the most abnormal value of each variable were constructed on a
      scale from 0 to 4 so that a value of 0 represented essentially normal function
      and was associated with an ICU mortality rate of < 5%, whereas a value of 4
      represented marked functional derangement and an ICU mortality rate of > or =
      50%. These intervals were then tested on the second half of the data set (the
      validation set). Maximal scores for each variable were summed to yield a Multiple
      Organ Dysfunction Score (maximum of 24). This score correlated in a graded
      fashion with the ICU mortality rate, both when applied on the first day of ICU
      admission as a prognostic indicator and when calculated over the ICU stay as an
      outcome measure. For the latter, ICU mortality was approximately 25% at 9 to 12
      points, 50% at 13 to 16 points, 75% at 17 to 20 points, and 100% at levels of >
      20 points. The score showed excellent discrimination, as reflected in areas under
      the receiver operating characteristic curve of 0.936 in the development set and
      0.928 in the validation set. The incremental increase in scores over the course
      of the ICU stay (calculated as the difference between maximal scores and those
      scores obtained on the first day [i.e., the delta Multiple Organ Dysfunction
      Score]) also demonstrated a strong correlation with the ICU mortality rate. In a
      logistic regression model, this incremental increase in scores accounted for more
      of the explanatory power than admission severity indices. CONCLUSIONS: This
      multiple organ dysfunction score, constructed using simple physiologic measures
      of dysfunction in six organ systems, mirrors organ dysfunction as the intensivist
      sees it and correlates strongly with the ultimate risk of ICU mortality and
      hospital mortality. The variable, delta Multiple Organ Dysfunction Score,
      reflects organ dysfunction developing during the ICU stay, which therefore is
      potentially amenable to therapeutic manipulation. (ABSTRACT TRUNCATED)

PMID- 7587230
TI  - High-risk intrahospital transport of critically ill patients: safety and outcome
      of the necessary "road trip".
AB  - OBJECTIVE: Intrahospital transport of critically ill patients is often necessary
      for optimal patient care. However, transport of intensive care unit (ICU)
      patients within the hospital has been associated with a high rate of potentially
      detrimental complications. This study was designed to determine the occurrence
      rate of transport-related complications and to determine if these complications
      have any effect on patient morbidity and mortality. DESIGN: Prospective, cohort
      matched study. SETTING: A 780-bed urban, university teaching hospital. PATIENTS:
      Seven hundred fifty-nine surgical ICU patients. INTERVENTIONS: One hundred
      seventy-five patients were transported out of the surgical ICU for diagnostic
      testing or operative interventions deemed necessary by their surgical or critical
      care team. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health
      Evaluation (APACHE) II and APACHE III scores were determined 24 hrs after
      admission. Transport patients were stratified into low-risk and high-risk
      transport groups. Patients were considered a high-risk transport if they required
      positive end-expiratory pressure of > 5 cm H2O, a continuous infusion of
      dobutamine, or a continuous infusion of norepinephrine. The high-risk group was
      further stratified into three groups based on the number of defined treatment
      regimens required to maintain the patient during transport. The patients were
      then followed during their transport for any potentially detrimental
      complications, such as a need for an increased dose of vasoactive medications,
      loss of intravenous access, a need for additional ventilatory support, or
      cardiopulmonary arrest. APACHE-matched control cohorts were identified as
      patients who did not leave the surgical ICU. The overall occurrence rate of
      complications was similar in the two groups (low-risk group, 6.3%; high-risk
      group, 5.5%). The mortality rate for all transport patients was 28.6%, which was
      statistically higher (p < .01) than the mortality rate for all control patients
      (11.4%). However, there was no mortality as a direct result of a transport. The
      overall mortality rate (10.9%) of the low-risk group was not significantly
      different from the APACHE-matched controls (6.0%). The overall mortality rate
      (51.4%) in the high-risk group was significantly higher (p < .01) than the APACHE
      matched controls, but was not statistically higher than predicted mortality (p =
      .416). Both the low-risk and the high-risk groups stayed in the surgical ICU
      three times as long as the APACHE-matched control cohorts. CONCLUSIONS:
      Intrahospital transport of critically ill patients is safe and carries a low risk
      of detrimental complications. Although patients requiring "high-risk"
      interventions experienced a higher mortality rate than did APACHE-matched
      controls, the increase in mortality does not appear to be directly related to the
      intrahospital transport. Patients requiring transport out of the surgical ICU are
      a more critically ill group of patients. These patients require a greater length
      of stay in the surgical ICU and may experience an increased mortality rate by
      virtue of the severity of their illness.

PMID- 7587231
TI  - Predictors of between-method differences in cardiac output measurement using
      thoracic electrical bioimpedance and thermodilution.
AB  - OBJECTIVES: To evaluate the usefulness of transthoracic electrical bioimpedance
      in trending changes in cardiac output after cardiac surgery, and to identify
      predictors of differences between cardiac output measured by thermodilution and
      transthoracic electrical bioimpedance methods. DESIGN: Prospective repeated
      measures study. SETTING: University-affiliated tertiary care center. PATIENTS:
      Thirty-four adult patients undergoing elective cardiac surgery with routine
      pulmonary artery catheter placement. INTERVENTIONS: Simultaneous paired cardiac
      output measurements by transthoracic electrical bioimpedance and thermodilution
      were made at four time points: within 2 hrs of intensive care unit (ICU)
      admission; when the patient reached a normothermic temperature; after extubation;
      and 24 hrs after ICU admission. MEASUREMENTS AND MAIN RESULTS: Mean measurements
      by each method over time did not differ, except at ICU admission, when compared
      by repeated-measures analysis of variance. For each time point, bias and
      precision between methods were calculated. Bias calculations ranged from 0.02 to
      0.21 L/min/m2. Precision calculations ranged from 1.06 to 1.52 L/min/m2.
      Predictors of between-method differences identified by a multiple regression
      model of hemodynamic variables were: increased systemic vascular resistance
      index, decreased mean arterial pressure (MAP), and the presence of atrial or
      ventricular pacing. CONCLUSIONS: While mean postoperative cardiac output
      measurements did not differ by method over time, agreement between transthoracic
      electrical bioimpedance and thermodilution methods was poor in the immediate
      postoperative period, with precision calculations indicative of clinically
      significant differences. Increased systemic vascular resistance index and
      decreased MAP were predictive of larger between-method differences.

PMID- 7587232
TI  - Effect of heparin on whole blood activated partial thromboplastin time using a
      portable, whole blood coagulation monitor.
AB  - OBJECTIVES: To evaluate the responsiveness of whole blood activated partial
      thromboplastin time (aPTT) to varying heparin doses in vitro and to examine the
      ex vivo relationship of whole blood aPTT to plasma heparin concentration. DESIGN:
      Prospective, controlled laboratory study. SETTING: Surgical suites and laboratory
      at a tertiary center. PATIENTS: Surgical patients and volunteers at a tertiary
      center were eligible for inclusion in this study. In vitro evaluation was
      performed using specimens obtained from each of five, healthy volunteers. Ex vivo
      evaluation was performed using specimens obtained from 30 cardiac surgical
      patients before and after systemic administration of heparin for extracorporeal
      circulation. INTERVENTIONS: Blood specimens were obtained from volunteers and
      added to syringes containing varying amounts of unfractionated porcine heparin
      for in vitro evaluation. For ex vivo evaluation, blood specimens were obtained
      from patients before and after systemic administration of 20 U/kg of heparin.
      MEASUREMENTS AND MAIN RESULTS: For the in vitro evaluation, specimens were
      divided into two aliquots after mixing with varying amounts of unfractionated
      porcine heparin. One aliquot was used to measure whole blood aPTT using a whole
      blood coagulation monitor immediately after blood collection and 3 mins later,
      and a second aliquot was used to determine plasma aPTT with a conventional,
      laboratory-based assay. Linear regression analysis demonstrated a high
      correlation (r = .94; r2 = .88) between aPTT assay systems and bias analysis
      demonstrated a mean aPTT measurement difference of 1.6 secs with +/- 2 SD limits
      of -15 to +18.2 secs. As indicated by comparable regression slopes, the in vitro
      aPTT responsiveness to increasing heparin concentration was similar with the two
      assay systems among individual subjects. Whole blood aPTT measurements after 3
      mins of blood specimen storage were similar to immediate measurements. For ex
      vivo evaluation, blood specimens obtained from patients before and after systemic
      administration of heparin were divided into two aliquots. One aliquot was used to
      measure whole blood aPTT in duplicate and a second aliquot was used to measure
      plasma heparin concentration with an antifactor X active chromogenic assay. A
      high correlation (r = .89; r2 = .79) between whole blood aPTT and plasma heparin
      concentration was observed. CONCLUSIONS: Heparin responsiveness of whole blood
      aPTT, measured with a portable whole blood coagulation monitor, is similar to
      that of conventional laboratory aPTT over a clinically relevant range of heparin
      concentrations in vitro and ex vivo. On-site whole blood aPTT measurements should
      be useful in clinical situations requiring rapid aPTT results.

PMID- 7587233
TI  - T-lymphocyte subsets in acute illness.
AB  - OBJECTIVES: To determine the range of T-lymphocyte subsets (CD4, CD8, and CD4/CD8
      ratios) in acutely ill, hospitalized patients and to determine whether these
      concentrations correlate with illness severity, survival rate, or
      immunodepression. DESIGN: Cross-sectional study, comparing Acute Physiology and
      Chronic Health Evaluation II (APACHE II) scores and the calculated, disease
      specific, predicted mortality rate with T-lymphocyte subsets. SETTING: Urban
      county hospital intensive care unit (ICU), serving as the designated trauma
      center. PATIENTS: One hundred two consecutively admitted ICU patients (72 medical
      and 30 surgical). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient
      clinical data, APACHE II scores, and their associated predicted mortality rate
      were recorded. Blinded human immunodeficiency virus (HIV) and lymphocyte testing
      was performed on samples from all patients on ICU admission. Despite only three
      (2.9%) of 102 patients testing positive for HIV antibodies, 41% (42/102) of
      patients had CD4 concentrations of < 400 cells/microL, and 29% (29/102) had CD4
      concentrations of < 300 cells/microL. Mean CD8 concentrations were even lower,
      compared with normal laboratory values, resulting in a slight increase in CD4/CD8
      ratios, although 16% (16/102) of patients had a CD4/CD8 ratio of < 1. CD4 counts
      were linearly related to total lymphocyte concentrations (Pearson correlation
      coefficient = 0.948), but no relationship was found between total lymphocyte or
      lymphocyte subset counts and APACHE II score, predicted mortality rate, or
      survival rate. CONCLUSIONS: Acute illness alone, in the absence of HIV infection,
      can be associated with profound decreases of T-lymphocyte populations. This
      problem is unpredictable and does not correlate with severity of illness,
      predicted mortality rate, or actual mortality rate. No conclusions regarding HIV
      serostatus or survival can be made based on single measurements of T-cell
      concentrations in acutely ill hospitalized patients.

PMID- 7587234
TI  - Deficiency of complement factor C5 reduces early mortality but does not prevent
      organ damage in an animal model of multiple organ dysfunction syndrome.
AB  - OBJECTIVE: To evaluate the role of complement factor C5 in a model of zymosan
      induced multiple organ dysfunction syndrome. DESIGN: Experimental animal study.
      SETTING: Central animal laboratory of a university hospital. SUBJECTS: Twenty
      five C5-deficient B2D10/Old and 25 C5-sufficient B2D10/New mice. INTERVENTIONS:
      On day 0, all mice received an intraperitoneal injection with zymosan suspended
      in paraffin in a dose of 1 mg/g body weight. MEASUREMENTS AND MAIN RESULTS:
      Between days 0 and 12, biological parameters (temperature, body weight, and
      clinical condition) were measured daily and mortality was monitored. Clinical
      condition was assessed as a symptom score by blindly grading the degree of
      lethargy, conjunctivitis, diarrhea, and ruffled fur of each mouse on a 2-point
      scale (maximum score of 4). On day 12, all surviving mice were killed and
      relative organ weights of lungs, liver, spleen, and kidneys were calculated.
      Relative organ weight was defined as (organ weight/body weight) x 100%. Zymosan
      administration induced a typical triphasic illness. Deterioration of the clinical
      condition, as indicated by the symptom score, and the decrease in temperature and
      body weight in the acute phase were all significantly less severe in C5-deficient
      mice (p < .005). In the late phase, no differences could be noticed in the
      courses of these biological parameters. Overall mortality was 2 (8%) of 25 in C5
      deficient mice and 8 (32%) of 25 in C5-sufficient mice (p = .049), a difference
      that was mainly due to a difference in the acute phase. Organ damage, assessed as
      the relative organ weights, did not show any statistical differences for any
      organ between both strains. CONCLUSIONS: Complement factor C5 appears to play an
      important role in the acute hyperdynamic septic response in this model. However,
      deficiency of C5 could not prevent organ damage in the late multiple organ
      dysfunction syndrome phase. This finding suggests that other factors must be more
      important in the development of the inflammatory response leading to multiple
      organ dysfunction syndrome.

PMID- 7587236
TI  - Monitoring of tissue oxygenation in shock: an experimental study in pigs.
AB  - OBJECTIVE: To evaluate different methods and markers for assessing adequacy of
      tissue oxygenation in shock. DESIGN: Prospective, controlled animal trial. Two
      groups of six pigs, subjected to either a superior mesenteric artery occlusion
      shock or a hemorrhagic shock. A third group of five pigs served as controls.
      SETTING: Hospital animal research laboratory. SUBJECTS: Anesthetized, ventilated,
      juvenile, domestic pigs. INTERVENTIONS: Clamping of the superior mesenteric
      artery for 5 hrs, followed by reperfusion or withdrawal of blood to achieve a
      mean arterial pressure of 50 mm Hg for 3 hrs was performed, followed by
      resuscitation using the withdrawn whole blood. Invasive hemodynamic monitoring
      with arterial and pulmonary artery catheters was done. A tonometer was placed in
      the terminal ileum. MEASUREMENTS AND MAIN RESULTS: Ileal intramucosal pH,
      systemic base excess (or deficit), lactate concentration in systemic venous and
      arterial blood as well as in portal blood, ascitic fluid, and thoracic duct
      lymph, hemodynamics, and oxygen-related variables were measured. Five hours of
      intestinal ischemia caused no significant changes compared with the control group
      with regard to base excess or any of the hemodynamic or oxygen-related variables
      measured. However, lactate concentrations in the ascitic fluid and intramucosal
      pH were significantly altered within 1 hr of regional ischemia. Lactate
      concentration in the thoracic duct lymph was significantly increased after 2 hrs
      of ischemia, while lactate concentrations in the portal, systemic, and arterial
      blood were significantly increased after 2 hrs of regional ischemia. Reperfusion
      was associated with a high mortality rate, and only one animal survived the
      reperfusion period. In the hemorrhagic shock group, cardiac output and mean
      arterial pressure were significantly (intentionally) decreased 60 mins after the
      hemorrhage, while the heart rate, base excess, and systemic and portal blood
      lactate concentrations were significantly increased after 2 hrs of general
      hypoperfusion compared with those values in the control group. Ileal intramucosal
      pH, mixed venous oxygen saturation, oxygen delivery, oxygen extraction, and
      lactate concentrations in the arterial blood and thoracic duct lymph were
      significantly different from those values in the control group 3 hrs after the
      onset of hemorrhagic shock. Reperfusion induced a normalization of the
      hemodynamic and metabolic status of the animals. CONCLUSION: Many conventional
      markers of tissue hypoxia are useful when assessing general hypoperfusion,
      whereas intestinal intramucosal pH is the only reliable and clinically useful
      indicator of inadequate regional intestinal tissue oxygenation.

PMID- 7587235
TI  - Autonomic modulation of heart rate variability during endotoxin shock in rabbits.
AB  - OBJECTIVE: Gram-negative septic shock is associated with severe hypotension and
      autonomic cardiovascular dysfunction. We hypothesized that in an anesthetized
      rabbit model of endotoxin shock, autonomic modulation of cardiac activity, as
      measured by power spectral analysis of heart rate (HR) variability, would be
      decreased compared with the anesthetized control rabbits. DESIGN: Experimental,
      comparative study. SETTING: Laboratory of a university hospital. SUBJECTS:
      Fourteen adult male New Zealand white rabbits (2.7 to 3.1 kg body weight) were
      studied under anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      studied the absolute and temporal changes in HR power spectra and plasma
      catecholamine concentrations in eight experimental and six control New Zealand
      white rabbits during Escherichia coli endotoxin-induced shock. HR, respirations,
      arterial blood pressure (BP), HR power spectra, and plasma catecholamine
      concentrations were measured at 5- to 10-min intervals for 60 mins in control
      rabbits or until the mean arterial pressure (MAP) decreased by > or = 20 mm Hg in
      experimental rabbits. There were no differences in basal HR, respiratory rate,
      BP, HR power spectra, or catecholamine concentrations between groups. After
      endotoxin administration, MAP decreased (82 +/- 7 vs. 62 +/- 5 mm Hg; p < .05) as
      did log low-frequency HR power (-2.14 +/- 2.46 vs. -2.20 +/- 2.48 beats/min2; p <
      .05). Low-frequency HR power and MAP remained unchanged in control animals. Log
      high-frequency HR power decreased in control and experimental rabbits (-1.02 +/-
      1.34 vs. -1.69 +/- 2.12 [control], p < .05; -1.53 +/- 2.19 vs. -2.19 +/- 2.85
      beats/min2 [experimental], p < .05). While there was an inverse relationship
      between low- and high-frequency HR power and MAP, the direction of change was
      opposite in six of six rabbits in the control group and in six of eight rabbits
      in the experimental group. Plasma catecholamine concentrations did not change
      during the experiment in either group. CONCLUSIONS: Sympathetic modulation of
      cardiac activity decreased, while the sympathomedullary response remained
      unchanged during endotoxin shock. We speculate that a concomitant decrease in low
      frequency HR power as MAP decreases may prove to be an early marker for impending
      shock.

PMID- 7587238
TI  - Improved oxygenation with reduced recirculation during venovenous extracorporeal
      membrane oxygenation: evaluation of a test catheter.
AB  - OBJECTIVE: To determine whether modifications of the original design of a double
      lumen, venovenous, extracorporeal membrane oxygenation (ECMO) catheter would
      reduce recirculation and improve oxygenation during venovenous ECMO. DESIGN:
      Prospective, interventional study. SETTING: The animal research laboratory at The
      Children's National Medical Center. SUBJECTS: Six newborn lambs, 1 to 7 days old
      and weighing 4.7 +/- 0.9 kg. INTERVENTIONS: Animals were anesthetized, intubated
      and ventilated. The ductus arteriosus was ligated. Femoral artery and vein,
      cephalic jugular vein, and pulmonary artery catheters were placed. After systemic
      heparinization, the test catheter (with venous drainage holes moved away from the
      arterial return holes) was placed in the right internal jugular vein and advanced
      into the right atrium. The animal was placed on ECMO and stabilized, with the
      ventilator settings decreased to a peak inspiratory pressure of 15 cm H2O, peak
      positive end-expiratory pressure of 5 cm H2O, respiratory rate of 15 breaths/min,
      and an FIO2 of 0.21. ECMO flows were increased in 100-mL increments from 200 to
      600 mL/min, with measurements taken 15 mins after each change. The test catheter
      was removed, the double-lumen, venovenous ECMO catheter was placed, and the
      studies were repeated. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial
      pressure, PaO2, jugular cerebral oxygen saturation, pulmonary artery oxygen
      saturation, mixed venous oxygen saturation, and postmembrane circuit pressures
      were measured at each study period. The test catheter improved oxygenation
      significantly, with higher systemic PaO2, higher pulmonary artery and cerebral
      oxygen saturations, and lower mixed venous oxygen saturations (indicating less
      recirculation). With the test catheter, PaO2 levels ranged from 62 +/- 6 torr
      (8.3 +/- 0.8 kPa) to 112 +/- 12 torr (14.9 +/- 1.6 kPa), compared with 46 +/- 4
      torr (6.1 +/- 0.5 kPa) to 59 +/- 2 torr (7.9 +/- 0.3 kPa) for the double-lumen,
      venovenous ECMO catheter (p < or = .001). These findings indicate that at all
      flow rates studied, less recirculation occurred with the test catheter than with
      the double-lumen, venovenous ECMO catheter. CONCLUSIONS: These findings indicate
      that the redesign of the double-lumen, venovenous ECMO catheter, as outlined in
      this study, resulted in a significant reduction of recirculation, thereby
      resulting in a significant improvement in oxygenation while on venovenous ECMO.
      This newly designed catheter makes venovenous ECMO more effective, and represents
      a design that could be used for pediatric and/or adult ECMO.

PMID- 7587237
TI  - Effects of methylene blue on oxygen availability and regional blood flow during
      endotoxic shock.
AB  - OBJECTIVE: We hypothesized that methylene blue, by inhibiting the activation of
      soluble guanylate cyclase mediated by nitric oxide, may reverse systemic
      hypotension, enhance myocardial function, and improve peripheral distribution of
      blood flow during endotoxic shock. DESIGN: Randomized, controlled, acute
      intervention study. SETTING: University intensive care laboratory. SUBJECTS:
      Twenty-one healthy, anesthetized, mongrel dogs, weighing 26 +/- 4 kg.
      INTERVENTIONS: Groups 1 (n = 7) and 2 (n = 7) received endotoxin (2 mg/kg iv)
      alone combined with increasing doses of 2.5, 5, 10, and 20 mg/kg iv of methylene
      blue. Each dose was administrated for 30 mins with a free interval of 30 mins.
      Group 3 (n = 7) served as a control group, receiving the same doses of methylene
      blue in the absence of endotoxin. All animals were given normal saline to keep
      cardiac filling pressures constant. Blood flow probes were placed around the
      superior mesenteric, renal, and femoral arteries to measure regional blood flow
      by ultrasonic technique. Data were collected every 30 mins during the study.
      MEASUREMENTS AND MAIN RESULTS: After endotoxemia, methylene blue increased
      systemic and pulmonary arterial pressure and vascular resistances in a dose
      dependent manner up to 10 mg/kg, but had no effect on cardiac index. At the
      highest dose, methylene blue decreased arterial pressure and systemic vascular
      resistance. At doses of methylene blue of < or = 10 mg/kg, mesenteric and femoral
      blood artery flow increased. At the highest dose of 20 mg/kg, femoral artery
      blood flow further increased, but mesenteric blood flow decreased. Renal artery
      blood flow was unaffected by methylene blue. In the absence of endotoxin,
      methylene blue at doses of 2.5 or 5 mg/kg did not alter mean arterial pressure,
      but reduced cardiac index, indicating an increase in systemic vascular
      resistance. In contrast, the higher doses of 10 or 20 mg/kg of methylene blue
      decreased mean arterial pressure and systemic vascular resistance. However,
      pulmonary arterial pressure and pulmonary vascular resistance increased in a dose
      dependent manner. Mesenteric and renal artery blood flow decreased but femoral
      blood flow increased. As in the presence of endotoxin, methylene blue induced
      dose-related increases in oxygen uptake and oxygen extraction ratio, but did not
      alter oxygen delivery. Methylene blue largely attenuated the endotoxin-induced
      increase in plasma nitrite concentrations. CONCLUSIONS: Low and moderate doses of
      methylene blue can significantly increase arterial blood pressure but not cardiac
      index during endotoxic shock. Methylene blue infusion may selectively increase
      mesenteric blood flow. High doses of methylene blue can worsen systemic
      hypotension, myocardial depression, and pulmonary hypertension after endotoxemia.

PMID- 7587239
TI  - Isoproterenol-dependent decrease in oxygen uptake and respiratory enzyme
      activities in rat myocardial tissue and mitochondria.
AB  - OBJECTIVE: Myocardial damage induced by isoproterenol is believed to be secondary
      to increased oxygen demands on the heart. Our objective was to test an additional
      primary action of isoproterenol on tissue and mitochondrial oxidative metabolism
      and to compare these effects with the effects of other adrenergic agents in the
      presence of adrenergic inhibitors. DESIGN: Prospective, dose-response study.
      SETTING: Research laboratory at a university hospital. SUBJECTS: Fifty Sprague
      Dawley female rats (200 to 350 g), slightly anesthetized with ether and divided
      into several groups. INTERVENTIONS: In 26 rats, the heart was removed, cut into
      fine slices (0.5-mm thickness), and placed in an ice-cold buffer. In 22 animals,
      the hearts were perfused in the Langendorff manner and chopped and processed for
      mitochondrial studies. MEASUREMENTS AND MAIN RESULTS: We determined the
      following: a) the direct "in vitro" effects of isoproterenol and related
      catecholamines on normal oxygen uptake using myocardial slices; b) rat heart
      oxygen consumption and mitochondrial oxygen uptake from isolated organs, perfused
      with isoproterenol; c) measurements of enzyme activities in submitochondrial
      particles from the same perfused hearts; and d) the direct effects of
      isoproterenol on normal mitochondria isolated from normal nonperfused hearts. The
      oxygen uptake was determined polarographically with a Clark-type electrode and
      enzymatic activities were assayed by spectrophotometric reduction of cytochrome c
      at 550 nm with different mitochondrial substrates. Isoproterenol (0.01 to 100 nM)
      decreased the oxygen uptake by the heart slices in a dose-dependent manner. In
      comparison, epinephrine or norepinephrine per se did not change the parameter.
      However, with the addition of alpha-adrenergic receptor inhibitors, oxygen uptake
      decreased to values similar to those values obtained with isoproterenol. Also,
      mitochondria isolated from hearts perfused with isoproterenol had decreased state
      3 respiratory rates (by 50%) and decreased respiratory control ratios (by 30%),
      without changes in adenosine 5'-diphosphate/oxygen ratios. The respiratory chain
      enzyme activities were also lowered. CONCLUSIONS: The data suggest that while
      isoproterenol increases "in vivo" oxygen uptake by the working rat heart,
      isoproterenol can simultaneously decrease maximal adenosine 5'-diphosphate
      induced mitochondrial oxygen uptake and in vitro myocardial tissue oxygen uptake,
      probably by modifying the mitochondrial respiratory enzymes. This action could be
      counteracted by alpha-adrenergic agonist effects.

PMID- 7587242
TI  - A model for technology assessment as applied to closed loop infusion systems.
      Technology Assessment Task Force of the Society of Critical Care Medicine.
AB  - OBJECTIVES: To test a model for the assessment of critical care technology on
      closed loop infusion control, a technology that is in its early stages of
      development and testing on human subjects. DATA SOURCES: A computer-assisted
      search of the English language literature and reviews of the gathered data by
      experts in the field of closed loop infusion control systems. STUDY SELECTION:
      Studies relating to closed loop infusion control that addressed one or more of
      the questions contained in our technology assessment template were analyzed.
      Study design was not a factor in article selection. However, the lack of well
      designed clinical outcome studies was an important factor in determining our
      conclusions. DATA EXTRACTION: A focus person summarized the data from the
      selected studies that related to each of the assessment questions. The
      preliminary data summary developed by the focus person was further analyzed and
      refined by the task force. Experts in closed loop systems were then added to the
      group to review the summary provided by the task force. These experts' comments
      were considered by the task force and this final consensus report was developed.
      DATA SYNTHESIS: Closed loop system control is a technological concept that may be
      applicable to several aspects of critical care practice. This is a technology in
      the early stages of evolution and much more research and data are needed before
      its introduction into usual clinical practice. Furthermore, each specific
      application and each device for each application (e.g., nitroprusside infusion,
      ventilator adjustment), although based on the same technological concept, are
      sufficiently different in terms of hardware and computer algorithms to require
      independent validation studies. CONCLUSIONS: Closed loop infusion systems may
      have a role in critical care practice. However, for most applications, further
      development is required to move this technology from the innovation phase to the
      point where it can be evaluated so that its role in critical car practice can be
      defined. Each application of closed loop infusion systems must be independently
      validated by appropriately designed research studies. Users should be provided
      with the clinical parameters driving each closed loop system so that they can
      ensure that it agrees with their opinion of acceptable medical practice. Clinical
      researchers and leaders in industry should collaborate to perform the
      scientifically valid, outcome-based research that is necessary to evaluate the
      effect of this new technology. The original model we developed for technology
      assessment required the addition of several more questions to produce a complete
      analysis of an emerging technology. An emerging technology should be
      systematically assessed (using a model such as the model developed by the Society
      of Critical Care Medicine), before its introduction into clinical practice in
      order to provide a focus for human outcome validation trials and to minimize the
      possibility of widespread use of an unproven technology.

PMID- 7587241
TI  - Airway leak size in neonates and autocycling of three flow-triggered ventilators.
AB  - OBJECTIVES: To define the spectrum of airway leak in the neonatal population and
      examine the occurrence rate of autocycling of three flow-triggered ventilators
      within the defined spectrum of airleak. DESIGN: Prospective study of pulmonary
      function tests of intubated infants and performance of ventilators on a
      mechanical lung model under simulated clinical conditions. SETTING: An intensive
      care nursery and research laboratory at a university medical center.
      INTERVENTIONS: Analysis of pulmonary function tests of 50 infants from our
      intensive care nursery, selected at random, to determine size of airleak around
      the endotracheal tube. The rate of autocycling of ventilators due to airleak of
      variable size, while connected to a test lung was subsequently studied.
      Ventilators were set on the assist-control mode with the control rate set at 0
      breath/min. Each ventilator was studied at the maximum sensitivity setting, which
      was 1, 2.5, and 3.3 mL/sec for each ventilator, respectively, and also at
      decreased sensitivity settings to 10 mL/sec. Airleak size was varied (10% to 45%)
      by increasing the orifice size within the endotracheal tube adapter/connector
      sideport and/or the positive end-expiratory pressure level (2 to 8 cm H2O).
      MEASUREMENTS AND MAIN RESULTS: In the infants, airleak size was calculated during
      synchronous ventilator breaths as (inspiratory minus expiratory) tidal
      volume/expiratory tidal volume x 100% (n = 25 +/- 11 breaths/patient). Mean +/-
      SD leak size in the infants was 15.6 +/- 11%. A minimal leak size of 0 to 10% was
      present in 15 (30%) infants, leak size of 10% to 20% in 24 (48%), leak size of
      20% to 30% in seven (14%), and leak size > 30% in four (8%) infants. The relative
      tendency of the three ventilators to autocycle is a function of the maximum
      sensitivity setting, which varies with each ventilator. The ventilator with the
      maximum sensitivity set at 1 mL/sec autocycled rapidly (> or = 40 breaths/min) at
      leak size of > 10%; the ventilator set at 2.5 mL/sec autocycled rapidly at leak
      size of > or = 20%; and the ventilator set at 3.3 mL/sec autocycled rapidly at
      leak size of > or = 30%. In all ventilators, the rate of autocycling increased
      with increased leak size, and decreased with decreased sensitivity setting.
      CONCLUSIONS: Flow-triggered ventilators are susceptible to autocycling due to
      flow compensation to maintain positive end-expiratory pressure levels in the
      presence of an airway leak. The difference in autocycling is due to the maximum
      sensitivity setting of each ventilator, and not to intrinsic ventilator
      flowsensing or other software mechanisms. The 3.3-mL/sec setting was the least
      prone to autocycling and seems appropriate. The ventilator set at 2.5 mL/sec at
      the time of this study has been released instead at 4 mL/sec, due to these
      findings. The ventilator with the maximum setting at 1 mL/sec autocycled readily
      at leak size of > or = 10%. Since such a leak size was present in 70% of infants,
      this setting should be used with caution. Using these guidelines, autocycling of
      all three ventilators is likely to occur mainly in 8% of infants with leak size
      of > 30%. In these cases, lowering the sensitivity setting and/or positive end
      expiratory pressure level may decrease autocycling, or may necessitate
      reintubation with a larger endotracheal tube.

PMID- 7587240
TI  - Qualitative comparison of carbon dioxide-induced change in cerebral near-infrared
      spectroscopy versus jugular venous oxygen saturation in adults with acute brain
      disease.
AB  - OBJECTIVE: To compare carbon dioxide-induced changes in cerebral oxy- and
      deoxyhemoglobin, measured by near-infrared spectroscopy, with those changes in
      jugular venous oxygen saturation in adult patients with acute brain disease.
      DESIGN: A prospective study. SETTING: The medical and surgical intensive care
      unit of a university hospital. PATIENTS: Nine patients with head trauma (n = 4),
      cerebrovascular disease (n = 3), and meningitis (n = 2). A total of ten
      measurements were done, while PaCO2 was increased from hypocapnia toward
      normocapnia in the nine patients. INTERVENTIONS: Arterial and jugular bulb
      catheterization, and intracranial pressure monitoring were performed as a part of
      the clinical intervention. An increase in PaCO2 was obtained by inhalation of CO2
      and, if necessary, by reducing the ventilator rate. MEASUREMENTS AND MAIN
      RESULTS: In each patient, the position of the jugular bulb catheter was
      ascertained by skull roentgenography. Near-infrared spectroscopic values for oxy-
      and deoxyhemoglobin were set at zero at the beginning of the study. An increase
      in PaCO2 from 29 +/- 1 (SEM) torr (3.9 +/- 0.2 kPa) to 39 +/- 2 torr (5.2 +/- 0.3
      kPa) was accompanied by a significant increase in jugular venous oxygen
      saturation from 63 +/- 3% to 76 +/- 3%; a significant increase in oxyhemoglobin
      of 3.5 +/- 0.9 mumol/L (of the brain tissue); and a significant decrease in
      deoxyhemoglobin of 1.5 +/- 0.4 mumol/L. In nine of ten measurements, the slopes
      of changes in oxyhemoglobin against the slopes of change in jugular venous oxygen
      saturation were very similar. In one patient, oxyhemoglobin changed negligibly
      while jugular venous oxygen saturation increased by 20%. CONCLUSIONS: Jugular
      venous oxygen saturation consistently demonstrates cerebrovascular responsiveness
      to CO2. The direction and magnitude of changes in cerebral oxyhemoglobin,
      measured by near-infrared spectroscopy, were similar to those changes in jugular
      venous oxygen saturation in most of our cases. Interpretation of a negligible
      change in oxyhemoglobin in one patient, despite an obvious increase in jugular
      venous oxygen saturation, requires further study comparing near-infrared
      spectroscopy with standard techniques.

PMID- 7587244
TI  - Fellowship programs in critical care medicine: 1995-96.

PMID- 7587245
TI  - Energy expenditure of trauma patients.

PMID- 7587243
TI  - Standards of evidence for the safety and effectiveness of critical care
      monitoring devices and related interventions. Coalition for Critical Care
      Excellence: Consensus Conference on Physiologic Monitoring Devices.
AB  - OBJECTIVE: To devise alternatives to randomized, controlled, clinical trials that
      clinicians and research experts might find acceptable for approval of devices
      used in critical care medicine. DATA SOURCES: The Coalition for Critical Care
      Excellence (Coalition) of the Society of Critical Care Medicine organized a
      consensus conference in which recognized critical care researchers gave testimony
      to a panel of experts regarding the process for testing and approval of
      monitoring devices. DATA SELECTION: The expert panel used testimony from the
      presenters as the basis of discussions on the testing and approval process.
      Guiding principles and specific recommendations were made based on the testimony
      given. MAIN RESULTS: The panel determined the main constituents of the medical
      device approval process to be the Food and Drug Administration (FDA), the
      research and clinical community, and the device manufacturers. Distinctions were
      made between monitoring and interventional device categories. This document
      addresses only monitoring devices. Potential alternatives to randomized, blinded,
      controlled study designs for device testing are: a) nonblinded, randomized,
      management protocol-driven study; b) crossover study (n-of-one design); c)
      cluster-randomization (randomized by care unit); d) case-matched controls; e)
      mixed design; f) on/off design (before-after); and g) historical controls.
      CONCLUSIONS: The panel agreed on the following major recommendations: a) the FDA
      should accelerate publication of specific guidances for physiologic monitoring
      products with the assistance of the Coalition (priorities and content); b) more
      multidisciplinary research should be incorporated into new device studies; c)
      commonly accepted clinical tools may not need to be tested for clinical utility-
      these accepted tools should be identified by the Coalition; and d) an independent
      council of researchers and clinicians should make themselves available to serve
      as consultants to manufacturers regarding appropriate study design for the
      testing of devices.

PMID- 7587246
TI  - Current trends in brain trauma.

PMID- 7587247
TI  - Minnesota Impedance Cardiograph.

PMID- 7587249
TI  - Monophosphoryl lipid A and endotoxin tolerance.

PMID- 7587250
TI  - Monitoring neuromuscular blockade in the critically ill.

PMID- 7587248
TI  - Inverse ratio ventilation: simply an alternative, or something more?

PMID- 7587251
TI  - Left ventricular end-systolic pressure-volume indices revisited.

PMID- 7587252
TI  - Mortality risk prediction in sepsis.

PMID- 7587253
TI  - The "magic" of successful weaning from mechanical ventilation in chronic
      obstructive pulmonary disease.

PMID- 7587254
TI  - Effects of malignancy and interleukin-2 infusion on gut macromolecular
      permeability.
AB  - OBJECTIVE: Enhanced gut permeability has been shown in patients with advanced
      malignancy. The dramatic inflammatory shock syndrome produced by high-dose
      interleukin-2 immune therapy could further change gut barrier function. This
      study measured the effect of advanced renal cell carcinoma and malignant
      melanoma, and interleukin-2 treatment on gut permeability. DESIGN: Nonrandomized,
      controlled study. SETTING: University hospital. PATIENTS: Adults with metastatic,
      unresectable renal cell carcinoma or metastatic, malignant melanoma, and normal
      volunteers. INTERVENTIONS: Gut permeability was measured in patients with renal
      cell carcinoma or malignant melanoma before and during interleukin-2 infusions,
      using polyethylene glycol 3350 and polyethylene glycol 400. The polyethylene
      glycols were administered orally within 48 hrs of interleukin-2 therapy and the
      24-hr urine excretions were measured. MEASUREMENTS AND MAIN RESULTS: Increased
      permeability was seen in the baseline state of these patients (ratio of
      polyethylene glycol 3350 to polyethylene glycol 400 = 1.1 +/- 0.7 x 10(-2)) when
      compared with normal volunteers (ratio = 0.48 +/- 0.2 x 10(-2); p < .05).
      However, after interleukin-2 treatment, no further increase in permeability was
      seen (ratio = 1.4 +/- 0.8 x 10(-2)). CONCLUSIONS: Gut permeability to
      polyethylene glycol 3350 is enhanced in advanced malignancy. High-dose
      interleukin-2 therapy does not further increase permeability of the gut.

PMID- 7587255
TI  - Influence of the quality of nursing on the duration of weaning from mechanical
      ventilation in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the influence of nursing on the duration of weaning from
      mechanical ventilation in patients with chronic obstructive pulmonary disease.
      DESIGN: Data were collected prospectively over a 1-yr period (study year) and
      compared with previously collected prospective data recorded in our chronic
      obstructive pulmonary disease database during a 5-yr period. SETTING: The medical
      intensive care unit (ICU) of a university hospital. PATIENTS: Eighty-seven
      patients with chronic obstructive pulmonary disease. Fifteen patients had chronic
      obstructive pulmonary disease that required mechanical ventilation for acute
      exacerbation of their disease (study year), and 72 were patients with chronic
      obstructive pulmonary disease from the previously collected data. INTERVENTIONS:
      The ICU course (duration of mechanical ventilation, mortality) was recorded, as
      well as several respiratory parameters (pulmonary function tests and arterial
      blood gases in stable conditions, and nutritional status), and they were compared
      with an "index of nursing." MEASUREMENTS AND MAIN RESULTS: We developed an "index
      of nursing", comparing the effective workforce of the nurses (number and
      qualifications) with the ideal workforce required by the number of patients and
      the severity of their diseases. A value of 1.0 represented a perfect match
      between the needed and the effectively present nurses, whereas a lesser value
      signified a diminished available workforce. This index was compared with the
      complications and duration of weaning from mechanical ventilation. During the
      first 5 yrs, the duration of mechanical ventilation increased progressively from
      7.3 +/- 8.0 to 38.2 +/- 25.8 days (p = .006). A significant inverse correlation
      between the duration of mechanical ventilation and the nursing index (p = .025)
      was found. In the sixth comparative year, the number of nurses increased (nursing
      index = 1.05) and the duration of mechanical ventilation decreased to 9.9 +/- 13
      days (p < .001, yr 5 vs. yr 6). CONCLUSIONS: The quality of nursing appears to be
      a measurable and critical factor in the weaning from mechanical ventilation of
      patients with chronic obstructive pulmonary disease. Below a threshold in the
      available workforce of ICU nurses, the weaning duration of patients with chronic
      obstructive pulmonary disease increases dramatically. Therefore, very close
      attention should be given to the education and number of ICU nurses.

PMID- 7587257
TI  - Arterial blood sampling devices influence ionized calcium measurements.
AB  - OBJECTIVE: To determine the effect of commercially available arterial blood
      sampling devices on ionized calcium measurements. DESIGN: Prospective study.
      SETTING: Neurosurgical and shock-trauma intensive care units (ICU) at a tertiary
      care teaching hospital. PATIENTS: Fourteen patients admitted to the ICU. Each
      patient had an indwelling arterial catheter. INTERVENTIONS: Arterial blood
      sampling. MEASUREMENTS AND MAIN RESULTS: In 14 ICU patients, measurements of
      arterial blood ionized calcium concentrations were performed, using 12 different
      commercially available arterial blood sampling devices. Significant
      underestimation of ionized calcium in blood samples compared with the reference
      test tube (Vacutainer 45) was seen in seven of the devices. Arterial blood
      ionized calcium concentrations measured, using one commercially available
      syringe, were significantly higher compared with the reference test tube. There
      was no correlation between either the amount or type of heparin in the arterial
      blood sampling devices and arterial blood ionized calcium measurement.
      CONCLUSIONS: This study demonstrates that various commercially available arterial
      blood sampling devices alter arterial blood ionized calcium measurements. These
      alterations are clinically important because ICU patients may be treated with
      inappropriate calcium supplementation.

PMID- 7587256
TI  - Parenteral magnesium sulfate versus amiodarone in the therapy of atrial
      tachyarrhythmias: a prospective, randomized study.
AB  - OBJECTIVE: To compare the efficacy of parenteral magnesium sulfate vs. amiodarone
      in the therapy of atrial tachyarrhythmias in critically ill patients. DESIGN:
      Prospective, randomized study. SETTING: Multidisciplinary intensive care unit
      (ICU) at a university teaching hospital. PATIENTS: Forty-two patients, 21 medical
      and 21 surgical, of mean (SD) age 67 +/- 15 yrs and mean Acute Physiology and
      Chronic Health Evaluation II score of 22 +/- 6, with atrial tachyarrhythmias
      (ventricular response rate of > or = 120 beats/min) sustained for > or = 1 hr.
      INTERVENTIONS: After correction of the plasma potassium concentration to > or =
      4.0 mmol/L, patients were randomly allocated to treatment with either a)
      magnesium sulfate 0.037 g/kg (37 mg/kg) bolus followed by 0.025 g/kg/hr (25
      mg/kg/hr); or b) amiodarone 5 mg/kg bolus and 10 mg/kg/24-hr infusion.
      Therapeutic plasma magnesium concentration in the magnesium sulfate group was 1.4
      to 2.0 mmol/L. Therapeutic end point was conversion to sinus rhythm over 24 hrs.
      MEASUREMENTS AND MAIN RESULTS: At study entry (time 0), initial mean ventricular
      response rate and systolic blood pressure were 151 +/- 16 (SD) beats/min and 127
      +/- 30 mm Hg in the magnesium sulfate group vs. 153 +/- 23 beats/min and 123 +/-
      23 mm Hg in the amiodarone group, respectively (p = .8 and .65). Plasma magnesium
      (time 0) was 0.84 +/- 0.20 vs. 1.02 +/- 0.22 mmol/L in the magnesium and
      amiodarone group, respectively (p = .1). Eight patients had chronic dysrhythmias
      (magnesium 3, amiodarone 5). Excluding the two patient deaths (amiodarone group,
      time 0 + 12 to 24 hrs), no significant change in systolic blood pressure
      subsequently occurred in either group. In the magnesium group, mean plasma
      magnesium concentrations were 1.48 +/- 0.36, 1.82 +/- 0.41, 2.16 +/- 0.45, and
      1.92 +/- 0.49 mmol/L at time 0 + 1, 4, 12 and 24 hrs, respectively. By logistic
      regression, the probability of conversion to sinus rhythm was significantly
      better for magnesium than for amiodarone at time 0 + 4 (0.6 vs. 0.44), 12 (0.72
      vs. 0.5), and 24 (0.78 vs. 0.5) hrs. In patients not converting to sinus rhythm,
      a significant decrease in ventricular response rate occurred at time 0 + to 0.5
      hrs (mean decrease 19 beats/min, p = .0001), but there was no specific treatment
      effect between the magnesium and the amiodarone groups; thereafter, there was no
      significant reduction in ventricular response rate over time in either group.
      CONCLUSIONS: Intravenous magnesium sulfate is superior to amiodarone in the
      conversion of acute atrial tachyarrhythmias, while initial slowing of ventricular
      response rate in nonconverters appears equally efficacious with both agents.

PMID- 7587258
TI  - Elastin fibers and the diagnosis of bacterial pneumonia in the adult respiratory
      distress syndrome.
AB  - OBJECTIVE: It has been inferred from previous work that 40% potassium hydroxide
      preparations of lower respiratory tract secretions that demonstrate elastin
      fibers have a 100% specificity and positive predictive value in diagnosing
      bacterial pneumonia in intubated, mechanically ventilated patients without the
      adult respiratory distress syndrome (ARDS). Our aim was to assess the specificity
      of 40% potassium hydroxide preparations in diagnosing bacterial pneumonia in
      patients with ARDS and suspected pneumonia. DESIGN: Prospective, case-referral
      clinical study. SETTING: Referral hospital. PATIENTS: Of 24 patients with ARDS
      who were intubated and mechanically ventilated with suspected bacterial
      pneumonia, 22 were assessable and evaluated for this report. INTERVENTIONS:
      Tracheo-bronchial aspirates were obtained from all patients and analyzed for
      elastin fibers using 40% potassium hydroxide. MEASUREMENTS AND MAIN RESULTS: Of
      the 22 assessable patients, ten patients did not have a complicating bacterial
      pneumonia. Six of these ten patients had potassium hydroxide preparations that
      demonstrated elastin fibers (false positives). The other four patients had
      preparations that did not demonstrate elastin fibers (true negatives).
      Specificity was 40%. CONCLUSION: Elastin fiber preparations are not specific for
      diagnosing bacterial pneumonia in patients with ARDS.

PMID- 7587259
TI  - Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated
      intravascular coagulation: relationship to multiple organ dysfunction syndrome.
AB  - OBJECTIVES: a) To investigate the relationships between tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator
      inhibitor-1, and disseminated intravascular coagulation (DIC); b) to determine
      the influence of DIC on the mortality rate, adult respiratory distress syndrome
      (ARDS), and multiple organ dysfunction syndrome; and c) to find a useful
      prognostic index for outcome. DESIGN: Prospective, case-control study. SETTING:
      General intensive care unit (tertiary care center) in a city hospital serving a
      population of 1.5 million people. PATIENTS: Fifty-eight trauma patients; 22 of
      the patients with DIC and 36 of the patients without DIC. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: TNF-alpha, IL-1 beta, plasminogen activator
      inhibitor-1 activity, and plasminogen activator inhibitor-1 antigen concentration
      were measured on the day of the injury, and on days 1, 3, and 5 after admission.
      The results of these measurements, demographic data, severity of illness score,
      mortality rate in the intensive care unit and frequencies of ARDS, multiple organ
      dysfunction syndrome, and sepsis were compared according to the occurrence of
      DIC. DIC patients were classified into subgroups of survivors and nonsurvivors,
      and the changes in plasminogen activator inhibitor-1 between subgroups were
      studied. The Acute Physiology and Chronic Health Evaluation II scores, the Injury
      Severity Scores, and the frequency of ARDS and multiple organ dysfunction
      syndrome were higher in the DIC patients. The mortality rate of the DIC patients
      was higher than the rate of the non-DIC patients (59.0% vs. 13.8%; p = .0009).
      TNF-alpha and IL-1 beta concentrations increased more in the DIC patients than in
      the non-DIC patients. Plasminogen activator inhibitor-1 activity and plasminogen
      activator inhibitor-1 antigen concentrations in the DIC patients, especially
      those values in the nonsurvivors, continued to be markedly high up to day 5 of
      admission. The most favorable prognostic value of plasminogen activator inhibitor
      1 for the prediction of death in all of the trauma patients and the DIC patients
      was determined on days 3 and 5, respectively. No significant correlation was
      noted between the two cytokines and plasminogen activator inhibitor-1.
      CONCLUSIONS: In the patients with trauma, DIC is a predictor of ARDS, multiple
      organ dysfunction syndrome, and death. TNF-alpha and IL-1 beta might be one of
      the causes of DIC, while plasminogen activator inhibitor-1 may be one of the
      aggravating factors of ARDS and multiple organ dysfunction syndrome. Plasminogen
      activator inhibitor-1 is a good predictor of death for posttrauma DIC patients.

PMID- 7587260
TI  - Difficulties in predicting outcome in cardiac surgery patients.
AB  - OBJECTIVE: To evaluate a novel combination of preoperative, intraoperative, and
      postoperative variables (including the Parsonnet, and the Acute Physiology and
      Chronic Health Evaluation II and III [APACHE II and III] scores) in cardiac
      surgery patients in order to predict hospital outcome, complications, and length
      of stay. DESIGN: Prospective survey. SETTING: Adult intensive care unit (ICU) at
      a tertiary care cardiothoracic surgery center. PATIENTS: All cardiac surgery
      patients admitted to the ICU over a 1-yr period. INTERVENTIONS: Medical history,
      Parsonnet score, intraoperative data (including bypass and ischemic times),
      APACHE II and III scores, complications, and outcome were collected for each
      patient. MEASUREMENTS AND MAIN RESULTS: One thousand eight patients were entered
      into the study. The mean Parsonnet score was 7.8 (range 0 to 33), mean APACHE II
      score 11.8 (range 2 to 33), and mean APACHE III score 42.5 (range 9 to 132). ICU
      mortality rate was 2.7% and hospital mortality rate was 3.8%. The mean APACHE II
      predicted risk of dying was 5.31%, which gave a standardized mortality ratio of
      0.71. The above scores were all statistically well correlated with hospital
      mortality. Further, a logistic regression model was developed for the probability
      of hospital death. This model (which included bypass time, need for inotropes,
      mean arterial pressure, urea, and Glasgow Coma Scale) had an area under the
      receiver operating characteristic curve of 0.87, while the Parsonnet score had an
      area of 0.82 and the APACHE II risk of dying had an area of 0.84. CONCLUSIONS:
      Cardiac surgery remains a difficult area for outcome prediction. A combination of
      intraoperative and postoperative variables can improve predictive ability.

PMID- 7587261
TI  - Pulmonary vasodilator responses to nicardipine: comparison with other
      vasodilators.
AB  - OBJECTIVES: To determine the direct effect of nicardipine on the pulmonary
      vascular bed of the intact-chest, spontaneously breathing cat, and to compare its
      effectiveness as a pulmonary vasodilator with the effectiveness of isoproterenol,
      nitroglycerin, and sodium nitroprusside. DESIGN: Prospective, controlled animal
      study. Each animal received all drugs in random order. SETTING: Animal laboratory
      at a university. SUBJECTS: Experiments were performed in vivo in ten intact
      chest, spontaneously breathing cats with controlled pulmonary blood flow and
      constant left atrial pressure, during conditions of increased pulmonary vascular
      tone. INTERVENTIONS: Five animals received intralobar injections of nicardipine
      (0.1 to 100 micrograms), nitroglycerin (0.1 to 10 micrograms), sodium
      nitroprusside (0.1 to 100 micrograms), and isoproterenol (0.01 to 1 microgram).
      Injections were made only when lobar arterial pressure had returned to baseline
      value. In another five animals, nicardipine, nitroglycerin, and sodium
      nitroprusside were administered intravenously as a continuous drug infusion in
      incremental doses titrated to produce a 20% reduction in mean systemic arterial
      pressure. Each dose was infused until lobar and systemic arterial pressures
      stabilized. A minimum, 30-min interval was allowed between the infusions of these
      drugs. MEASUREMENTS AND MAIN RESULTS: When pulmonary vascular tone was increased
      with a thromboxane A2 mimetic (analog), U46619 (a stable prostaglandin
      endoperoxide analog), intralobar injections of nicardipine caused dose-related
      decreases in lobar arterial pressure without affecting left atrial pressure. When
      compared with the other vasodilator agents, the order of potency was
      isoproterenol >> nitroglycerin > nicardipine = sodium nitroprusside.
      Isoproterenol reduced mean systemic arterial pressure 10 to 100 times greater
      than nitroglycerin, nicardipine, or sodium nitroprusside. However, there were no
      significant differences between the latter three drugs in producing a decrease in
      mean systemic arterial pressure. When infused intravenously, nitroglycerin caused
      the largest amount of pulmonary vasodilation for a given amount of systemic
      vasodilation. There were no significant differences between the pulmonary
      vasodilator responses of nicardipine and sodium nitroprusside. CONCLUSIONS: In
      this feline model of increased pulmonary vascular resistance, nicardipine exerts
      a direct vasodilator effect in vivo on the pulmonary vascular bed. Nicardipine,
      nitroglycerin, and sodium nitroprusside caused similar decreases in systemic
      arterial pressure. However, the pulmonary vasodilator effect was greater with
      nitroglycerin, which suggests that nitroglycerin is more vasoselective for the
      pulmonary vascular bed than nicardipine or sodium nitroprusside.

PMID- 7587262
TI  - Perfluorocarbon-associated gas exchange improves pulmonary mechanics,
      oxygenation, ventilation, and allows nitric oxide delivery in the hypoplastic
      lung congenital diaphragmatic hernia lamb model.
AB  - OBJECTIVES: To determine the efficacy of perfluorocarbon-associated gas exchange
      and the effects of inhaled nitric oxide during perfluorocarbon-associated gas
      exchange in the congenital diaphragmatic hernia lamb model. DESIGN: Prospective,
      nonrandomized, controlled, nonhuman trial. SETTING: Animal research facility.
      SUBJECTS: Fetal lambs of 16 time-dated pregnant ewes, at 80 days gestation (term
      140 to 145 days). MEASUREMENTS AND MAIN RESULTS: The congenital diaphragmatic
      hernia lamb model was created in 16 animals. Twelve animals survived to be
      studied. All animals were mechanically ventilated for 4 hrs with a time-cycled,
      pressure-limited ventilator. Perfluorocarbon-associated gas exchange was started
      after 15 mins of ventilation (n = 6). Blood gases were analyzed at 30 mins and
      then hourly. The perfluorocarbon-associated gas exchange animals had dynamic
      compliance and tidal volumes measured. After 1 hr, inhaled nitric oxide (80 parts
      per million) was delivered to the perfluorocarbon-associated gas exchange animals
      for 10 mins. All blood gas parameters, including pH (6.72 +/- 0.06 vs. 7.14 +/-
      0.07), PCO2 (186 +/- 12 vs. 70.5 +/- 16.7 torr [24.8 +/- 1.6 vs. 9.5 +/- 2.1
      kPa]), and PO2 (48 +/- 17 vs. 156 +/- 48 torr [6.4 +/- 2.3 vs. 20.8 +/- 6.4 kPa])
      were significantly improved in the perfluorocarbon-associated gas exchange
      treated group at 4 hrs (p < .005). Dynamic compliance (0.13 +/- 0.02 vs. 0.32 +/-
      0.06 mL/cm H2O/kg) and tidal volume (3.5 +/- 0.35 vs. 7.22 +/- 0.61 mL/kg) were
      also significantly (p < .001) increased in the perfluorocarbon-associated gas
      exchange group. In the perfluorocarbon-associated gas exchange animals, nitric
      oxide caused a significant (p < .05) increase in oxygenation and a reduction in
      pulmonary hypertension. This effect was reversed by stopping the inhaled nitric
      oxide. CONCLUSIONS: Perfluorocarbon-associated gas exchange significantly
      improved gas exchange, dynamic compliance, and tidal volumes. Furthermore,
      inhaled nitric oxide can be effectively delivered during perfluorocarbon
      associated gas exchange to reduce pulmonary hypertension and enhance oxygenation.

PMID- 7587263
TI  - Jugular ligation does not increase intracranial pressure but does increase
      bihemispheric cerebral blood flow and metabolism.
AB  - OBJECTIVES: To answer the following questions: a) Does jugular venous ligation
      (simulating venovenous extracorporeal life support) alter proximal jugular venous
      pressure, intracranial pressure, hemispheric cerebral blood flow, or cerebral
      metabolism? b) Does release of ligation reverse these effects? and c) What are
      the comparative effects of venous ligation alone vs. venous ligation in
      combination with arterial ligation? DESIGN: Prospective, randomized, laboratory
      investigation. SETTING: Multidisciplinary laboratory setting. SUBJECTS: Sixteen
      swine, weighing 8.1 to 12.1 kg, 3 to 4 wks of age. INTERVENTIONS: Sixteen swine
      were randomly assigned to two groups, utilizing a random sequence of vessel
      ligation. Nine swine underwent occlusion of the right internal and external
      jugular veins alone (venovenous ligation) followed by release of the occlusion
      and then occlusion of the right common carotid artery and the right internal and
      external jugular veins together (venoarterial ligation). The remaining seven
      swine underwent venoarterial ligation, followed by release of the occlusion and
      then venovenous ligation. In the experimental group in which venovenous ligation
      was performed first, the 5, and 30-min release periods after ligation were taken
      to represent the effects of draining the right jugular vein during venovenous
      extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: Data were obtained at
      baseline, 5, and 30 mins after each ligation/release period. Intracranial
      pressure, right and left internal jugular pressures/flow rates, and cerebral
      sinus lactate concentrations were measured. Cerebral blood flow was determined
      using 133Xe clearance methodology, and the cerebral metabolic rate was
      calculated. There were no significant differences between the ipsilateral
      internal jugular pressure or extracorporeal life support at 5 or 30 mins after
      venovenous or venoarterial ligation compared with baseline values or compared
      with the release of the ligation at 5 or 30 mins. There was a significant
      increase in right-side (44.7 +/- 2.0 vs. 38.8 +/- 2.4 mL/kg/min; p < .05) and
      left-side (42.9 +/- 2.3 vs. 38.7 +/- 1.9 mL/kg/min; p < .05) cerebral blood flow
      5 mins after venovenous ligation when compared with baseline values. Similarly,
      after venoarterial ligation, there was a significant increase in right-side (44.6
      +/- 2.2 vs. 38.8 +/- 2.4 mL/kg/min; p < .05) and left-side (43.9 +/- 1.5 vs. 38.7
      +/- 1.9 mL/kg/min; p < .05) and cerebral blood flow. Cerebral oxygen consumption
      was significantly increased after venovenous (2.7 +/- 0.2 to 3.2 +/- 0.2
      mL/kg/min; p < .05) and venoarterial (2.7 +/- 0.2 to 3.1 +/- 0.2 mL/kg/min; p <
      .05) ligation at 5 mins after ligation. This increase persisted at the 30-min
      period and after release of ligation. CONCLUSIONS: Ligation of the right jugular
      veins alone (venovenous ligation) or jugular veins and right carotid artery
      (venoarterial ligation) does not increase jugular venous pressures or
      intracranial pressure. However, this procedure does increase cerebral blood flow
      and cerebral oxygen consumption. These findings demonstrate that there is
      adequate decompression of the venous system by the cerebrovascular system and
      retrograde decompression during extracorporeal life support appears unwarranted.

PMID- 7587265
TI  - Respiratory mechanics and lung morphometry in severe pancreatitis-associated
      acute lung injury in rats.
AB  - OBJECTIVE: To develop and study an experimental model for severe pancreatitis
      associated lung injury. DESIGN: Prospective, randomized, controlled trial.
      SETTING: University pulmonary laboratory. SUBJECTS: Seventy-eight male Wistar
      rats. INTERVENTIONS: Pancreatitis was induced by taurocholate injection into the
      pancreatic duct. Data were compared with data from sham-operated animals.
      MEASUREMENTS AND MAIN RESULTS: Pulmonary mechanical measurements were performed
      in anesthetized and mechanically ventilated rats. Alveolar pressure was obtained
      by the alveolar capsule technique. Lungs were fixed at functional residual
      capacity by immersion in liquid nitrogen and were submitted to morphometric
      studies. Dynamic pulmonary elastance was found to be increased in the acute
      pancreatitis group (2.25 +/- 0.21 vs. 1.62 +/- 0.10 cm H2O/mL [p < .05]).
      Morphometric signs of distal airway contraction and vasoconstriction were
      observed. Increased intraalveolar edema rate (55.6 +/- 12.7% vs. 22.6 +/- 9.6% [p
      < .001]) was detected in the animals with acute pancreatitis. A high degree of
      pulmonary unevenness and polymorphonuclear infiltration were also detected in the
      lungs of the acute pancreatitis animals. CONCLUSIONS: In this severe pancreatitis
      associated lung injury model, the mechanical and morphologic alterations were
      similar to those alterations observed in the adult respiratory distress syndrome.
      This model may prove to be a useful tool to investigate mechanisms and mediators
      of the respiratory failure induced by acute pancreatitis and other forms of adult
      respiratory distress syndrome.

PMID- 7587264
TI  - Changes in gut intramucosal pH and gut oxygen extraction ratio in a porcine model
      of peritonitis and hemorrhage.
AB  - OBJECTIVE: To establish the relationship between gut intramucosal pH and blood
      flow to the gut, gut oxygen delivery, and gut oxygen extraction ratio in a
      porcine model of peritonitis and hemorrhage. DESIGN: Prospective, controlled
      study. SETTING: Experimental laboratory in a university teaching hospital.
      SUBJECTS: Thirty pigs of both sexes, weighing 15 to 22 kg. INTERVENTIONS: Animals
      were anesthetized, intubated, and mechanically ventilated. A flow probe was
      placed around the superior mesenteric artery for registration of blood flow. A
      tonometer was placed in the lumen of midileum for calculation of gut intramucosal
      pH. Hourly, for 5 hrs, blood samples were taken from mixed venous, mesenteric
      venous, and arterial blood. Five animals served as controls, ten animals had
      peritonitis induced by fecal instillation in the abdominal cavity, five were bled
      stepwise, five were bled rapidly (to a mean arterial pressure of 30 mm Hg), and
      five were bled rapidly and reinfused after 3 hrs. MEASUREMENTS AND MAIN RESULTS:
      Both peritonitis and hemorrhage caused decreases in gut blood flow and
      intramucosal pH. In mild peritonitis, the intramucosal pH decrease preceded that
      of blood flow. In all experimental groups, oxygen delivery decreased over time;
      in both mild and severe peritonitis, this decrease was preceded by a decrease of
      intramucosal pH. Intramucosal pH correlated well with gut oxygen extraction ratio
      in peritonitis (r2 = .86). In hemorrhage, there was a correlation of r2 = .66,
      but in intramucosal pH of < 7.12, a further decrease was accompanied only by
      minor changes in extraction ratio. CONCLUSIONS: Since a reduction in blood flow
      was preceded by a decrease in intramucosal pH, low intramucosal pH in peritonitis
      cannot be explained by low flow alone. Gut oxygen delivery proved to be a poor
      indicator of gut acidosis (i.e., low intramucosal pH). In peritonitis, a
      decreasing intramucosal pH was associated with an increasing oxygen extraction
      ratio. In hemorrhage, this association had a sharp deflection point below which a
      further decrease in intramucosal pH occurred concomitantly with an unchanged gut
      oxygen extraction ratio. Increased extraction ratio was not sufficient, not even
      initially, to maintain aerobic metabolism (i.e., unchanged intramucosal pH).

PMID- 7587266
TI  - Effects of hypertonic saline on myocardial function and metabolism in nonischemic
      and ischemic isolated working rat hearts.
AB  - OBJECTIVE: To study the direct effects of hypertonic saline on the function of
      non-ischemic and ischemic myocardium by the use of an isolated working rat heart
      model. DESIGN: A prospective, randomized, controlled study. SETTING: Animal
      laboratory at a university medical center. SUBJECTS: Adult Wistar rats (n = 32)
      of both sexes. INTERVENTIONS: The heart was excised via thoracotomy in
      anesthetized rats and prepared for antegrade perfusion at a constant heart rate
      in an antegrade perfusion apparatus at predetermined preloads and afterloads.
      Hearts were exposed to ischemia, ischemia followed by repeated hypertonic saline
      treatment, or repeated hypertonic saline without preceding ischemia. Myocardial
      ischemia was induced by decreasing the mean aortic pressure to 25 mm Hg.
      MEASUREMENTS AND MAIN RESULTS: Variables that were measured or calculated
      included the following: left atrial pressure; mean aortic pressure; heart rate;
      coronary flow; aortic flow; cardiac output; stroke volume; PO2, electrolyte
      content, osmolality, and lactate concentration of the perfusate and/or venous
      effluent; myocardial oxygen extraction; myocardial oxygen consumption; and
      myocardial lactate efflux. Ischemia resulted in pronounced impairment of
      myocardial function and metabolism. Hypertonic saline administration during
      ischemia induced an additional transient myocardial depression. In the
      nonischemic heart, a transient myocardial-depressant effect after hypertonic
      saline administration was also seen. CONCLUSIONS: The present results from an
      isolated working heart preparation show that hypertonic saline exerts myocardial
      depressive effects in the ischemic as well as in the nonischemic heart. Systemic
      rather than direct myocardial effects may therefore be responsible for the
      previously reported beneficial hemodynamic effects of hypertonic saline in shock
      treatment.

PMID- 7587267
TI  - Circulating concentrations and physiologic role of atrial natriuretic peptide
      during endotoxic shock in the rat.
AB  - OBJECTIVES: To determine if there are changes in circulating concentrations of
      endogenous atrial natriuretic peptide and the physiologic role of this peptide in
      endotoxic shock. DESIGN: A prospective, randomized, controlled animal trial.
      SETTING: University research laboratory. SUBJECTS: Anesthetized male Wistar rats,
      weighing 250 to 350 g. INTERVENTIONS: Six rats received 1.5 mg/kg body weight of
      lipopolysaccharide alone. Five rats received 1.5 mg/kg of lipopolysaccharide and
      200 microL/100 g body weight of rabbit anti-atrial natriuretic peptide serum.
      Another five rats received 1.5 mg/kg of lipopolysaccharide and normal rabbit
      serum in the same volume as the antiserum. MEASUREMENTS AND MAIN RESULTS: Plasma
      concentrations of atrial natriuretic peptide, arginine vasopressin, and
      aldosterone were measured, and changes in hemodynamic parameters and renal
      function were monitored in rats with endotoxic shock after catheterization of the
      right jugular vein. Urine volume, urine sodium excretion, urinary potassium
      excretion, and urine 3', 5'-cyclic guanosine monophosphate (cGMP) excretion were
      measured at 12-hr intervals. The plasma atrial natriuretic peptide concentration
      was slightly but significantly lower 30 mins after the lipopolysaccharide
      injection (114.8 +/- 9.0 pg/mL at 0 hr, 75.6 +/- 6.2 pg/mL at 30 mins, p < .01)
      and then began to increase, peaking at 6 hrs (752.8 +/- 104.5 pg/mL, p < .01 vs.
      0 time) and remaining at higher concentrations than before the preinjection
      value, up to 24 hrs. In contrast, acute spike-like increases of arginine
      vasopressin and aldosterone concentrations were observed 30 mins after the
      lipopolysaccharide injection, preceding the increase of the plasma atrial
      natriuretic peptide concentration. Measurements of urine volume and urine sodium
      excretion showed oliguria during the initial 12 hrs after the lipopolysaccharide
      injection, followed by diuresis and natriuresis during the subsequent 12 hrs. In
      addition, injection with anti-atrial natriuretic peptide serum in the diuretic
      phase 12 hrs after the lipopolysaccharide injection significantly inhibited the
      diuresis, natriuresis, and urine cGMP excretion in this model. Furthermore, the
      plasma aldosterone concentration 24 hrs after the lipopolysaccharide injection
      was significantly increased by the administration of the antisera. CONCLUSIONS:
      These findings suggest that endogenous atrial natriuretic peptide increases in
      the acute phase of endotoxic shock and plays an important role in water and
      electrolyte balance by regulating diuresis.

PMID- 7587268
TI  - Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac
      surgery.
AB  - OBJECTIVE: To evaluate the hemodynamic effects of intravenous milrinone in
      neonates with low cardiac output after cardiac surgery. DESIGN: Prospective
      cohort study. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Ten
      neonates with low cardiac output (cardiac index of < or = 3.0 L/min/m2) after
      corrective cardiac surgery were enrolled in the study. The neonates' ages ranged
      from 3 to 27 days (median 5) and their weights ranged from 2.0 to 4.8 kg (median
      3.7). The diagnoses were: transposition of the great arteries (n = 6, including
      two with ventricular septal defect), tetralogy of Fallot (n = 2), truncus
      arteriosus (n = 1), and total anomalous pulmonary venous connection (n = 1).
      INTERVENTIONS: Milrinone was intravenously administered in three stages: a)
      baseline stage, in which patients had a stable hemodynamic status, ventilation
      and gas exchange, hemostasis, and body temperature; b) loading stage, in which a
      50 microgram/kg intravenous loading dose of milrinone was administered over 15
      mins; and c) infusion stage, in which milrinone was continuously infused at 0.50
      microgram/kg/min for 30 mins. MEASUREMENTS AND MAIN RESULTS: The mean heart rate
      increased after the loading stage (149 +/- 13 to 163 +/- 12 beats/min, p < .01)
      but slowed during the infusion stage (154 +/- 11 beats/min, p < .01 vs. loading
      stage). Both right and left atrial pressures were lowered in all ten neonates.
      Compared with baseline, mean arterial pressure decreased after the loading stage
      (66 +/- 12 to 57 +/- 10 mm Hg, p < .01) but did not decrease further at the
      infusion stage (59 +/- 12 mm Hg); changes in mean pulmonary arterial pressure
      were comparable. Cardiac index increased from a baseline mean of 2.1 +/- 0.5 to
      3.0 +/- 0.8 L/min/m2 (p < .01) with the loading stage, and was maintained at 3.1
      +/- 0.6 L/min/m2 during the infusion stage. Systemic vascular resistance index
      decreased below baseline values with loading, from 2136 +/- 432 to 1336 +/- 400
      dyne.sec/cm5.m2 (p < .01), and pulmonary vascular resistance index also decreased
      with loading dose of milrinone, from 488 +/- 160 to 360 +/- 120 dyne.sec/cm5.m2
      (p < .01). There was no change in the rate pressure index, an indirect
      measurement of myocardial oxygen consumption, throughout the study. CONCLUSIONS:
      Administration of milrinone in neonates with low cardiac output after cardiac
      surgery lowers filling pressures, systemic and pulmonary arterial pressures, and
      systemic and pulmonary vascular resistances, while improving cardiac index.
      Milrinone increases heart rate without altering myocardial oxygen consumption.
      While milrinone appears to be effective and safe during short-term use, the
      relative distribution of inotropic and vasodilatory properties of milrinone
      remains to be elucidated.

PMID- 7587270
TI  - Guidelines for resident physician training in critical care medicine.
      Guidelines/Practice Parameters Committee, American College of Critical Care
      Medicine of the Society of Critical Care Medicine.
AB  - OBJECTIVES: To define a curriculum that outlines the core knowledge residents
      should possess upon completion of graduate training in order to be able to
      formulate and initiate a treatment plan for the critically ill patient. DATA
      SOURCES: Requirements for training program certification as outlined by the
      Accreditation Council for Graduate Medical Education; consensus opinion of adult
      and pediatric critical care physicians, nurses, and pharmacists with
      multidisciplinary experience and expertise in the critical care teaching
      environment. DATA SYNTHESIS: Because of concerns about variability between the
      training requirements of the five major specialties, and in keeping with the
      concept of critical care as a multispecialty discipline, preference was given to
      expert consensus opinion over certification requirements. CONCLUSIONS: A
      curriculum was developed that defines the core cognitive and procedural skills
      and special certifications residents should possess upon completion of residency
      training in order to be able to formulate and initiate a treatment plan for the
      critically ill patient. Special skills uniquely required for pediatric and adult
      patient populations are delineated.

PMID- 7587269
TI  - Prediction of mortality in neonates with congenital diaphragmatic hernia treated
      with extracorporeal membrane oxygenation.
AB  - OBJECTIVE: To determine if data collected by the Extracorporeal Life Support
      Organization Registry could be used to identify neonates with congenital
      diaphragmatic hernia who had a > 90% mortality rate, despite the use of
      extracorporeal membrane oxygenation (ECMO) support. DESIGN: We retrospectively
      reviewed data reported to the Extracorporeal Life Support Organization Registry
      on neonates with congenital diaphragmatic hernia. PATIENTS: Data regarding 1,089
      neonates with congenital diaphragmatic hernia reported to the Extracorporeal Life
      Support Organization Registry between 1980 and 1992 formed the basis of this
      study. All of the neonates studied had been treated with ECMO. This patient
      population includes neonates with right- and left-sided diaphragmatic hernia.
      This registry does not include neonates with congenital diaphragmatic hernia who
      were not treated with ECMO. MEASUREMENTS AND MAIN RESULTS: Of 1,089 neonates with
      congenital diaphragmatic hernia, 679 (62%) survived. There were no differences
      between the two groups in gender or in the year they were treated. Survival rate
      did not significantly increase over the years between 1980 and 1992. When
      compared with survivors, nonsurvivors were more immature (38 +/- 2 vs. 39 +/- 2
      wks; p = .01), had lower birth weights (3.0 +/- 0.5 vs. 3.21 +/- 0.53 kg; p =
      .001), were more often prenatally diagnosed (42% vs. 32%; p = .03), were
      cannulated at a younger age (31 +/- 54 vs. 40 +/- 50 hrs; p = .01), and had more
      severe respiratory compromise (higher peak pressures and PaCO2, lower PaO2
      values). Multivariate analysis showed that arterial pH and PaO2 just before ECMO,
      and birth weight, had the highest discriminant coefficients. By using these
      variables in a discriminant function (D[fx] = 0.68 x pH + 0.62 x birth weight +
      0.29 x PaO2; using standardized coefficients and variables), we could identify
      neonates who died with a sensitivity of 62%, a specificity of 63%, a positive
      predictive value of 50%, and a negative-predictive value of 74%. No single
      variable or combination of variables yielded better results. CONCLUSIONS:
      Although a number of factors identify neonates with diaphragmatic hernia as being
      at higher risk of dying despite ECMO support, data currently collected by the
      neonatal Extracorporeal Life Support Organization Registry do not allow
      clinicians to effectively discriminate nonsurvivors from survivors.

PMID- 7587271
TI  - Lithium-induced nephrogenic diabetes insipidus treated with intravenous
      ketorolac.

PMID- 7587272
TI  - Lipid deposition during the long-term infusion of propofol.

PMID- 7587273
TI  - Aluminum concentrations in critically ill children with renal impairment.

PMID- 7587274
TI  - Mechanical ventilators optimized for pediatric use decrease work of breathing and
      oxygen consumption during pressure-support ventilation.

PMID- 7587275
TI  - Teaching medical students in the intensive care unit: building houses with no
      foundation.

PMID- 7587276
TI  - Methylene blue infusion in septic shock.

PMID- 7587277
TI  - Methylene blue infusion in septic shock.

PMID- 7587278
TI  - Protein structure prediction: recognition of primary, secondary, and tertiary
      structural features from amino acid sequence.
AB  - This review attempts a critical stock-taking of the current state of the science
      aimed at predicting structural features of proteins from their amino acid
      sequences. At the primary structure level, methods are considered for detection
      of remotely related sequences and for recognizing amino acid patterns to predict
      posttranslational modifications and binding sites. The techniques involving
      secondary structural features include prediction of secondary structure, membrane
      spanning regions, and secondary structural class. At the tertiary structural
      level, methods for threading a sequence into a mainchain fold, homology modeling
      and assigning sequences to protein families with similar folds are discussed. A
      literature analysis suggests that, to date, threading techniques are not able to
      show their superiority over sequence pattern recognition methods. Recent progress
      in the state of ab initio structure calculation is reviewed in detail. The
      analysis shows that many structural features can be predicted from the amino acid
      sequence much better than just a few years ago and with attendant utility in
      experimental research. Best prediction can be achieved for new protein sequences
      that can be assigned to well-studied protein families. For single sequences
      without homologues, the folding problem has not yet been solved.

PMID- 7587280
TI  - Prediction of protein structural classes.
AB  - A protein is usually classified into one of the following five structural
      classes: alpha, beta, alpha + beta, alpha/beta, and zeta (irregular). The
      structural class of a protein is correlated with its amino acid composition.
      However, given the amino acid composition of a protein, how may one predict its
      structural class? Various efforts have been made in addressing this problem. This
      review addresses the progress in this field, with the focus on the state of the
      art, which is featured by a novel prediction algorithm and a recently developed
      database. The novel algorithm is characterized by a covariance matrix that takes
      into account the coupling effect among different amino acid components of a
      protein. The new database was established based on the requirement that the
      classes should have (1) as many nonhomologous structures as possible, (2) good
      quality structure, and (3) typical or distinguishable features for each of the
      structural classes concerned. The very high success rate for both the training
      set proteins and the testing-set proteins, which has been further validated by a
      simulated analysis and a jackknife analysis, indicates that it is possible to
      predict the structural class of a protein according to its amino acid composition
      if an ideal and complete database can be established. It also suggests that the
      overall fold of a protein is basically determined by its amino acid composition.

PMID- 7587279
TI  - New insight into the biochemical pathology of liver in choline deficiency.
AB  - A diet deficient in choline can cause liver cancer in rats. The previous work
      since 1932 emphasized the fat-removing ability of choline from the liver. There
      are other dietary factors, including methionine, which, like choline, can remove
      fat from the liver. These factors were termed as lipotropes. Since then, choline
      deficiency and lipotrope deficiency are used synonoumously. Recent work since
      1980 has clearly demonstrated that choline deficiency (CD) and lipotrope
      deficiency (LD) are not the same. Generation of free radicals, DNA alterations,
      liver cell death, and liver cancer that occur due to CD are not generated by LD.
      Generation of free radicals due to CD diet and some of the agents that counteract
      free radical action also prevent CD effects except for lipid accumulation in the
      liver. Despite the recent observations on the role of phospholipase A2 (PLA2) as
      the protector of the membranes, it has been found that by preventing the rise of
      PLA2 in the liver, cell death can be prevented. These new findings give choline a
      distinct role in liver cell death and cancer rather than the role of lipotrope. A
      new hypothesis linking dietary choline deficiency and liver cancer has been
      discussed.

PMID- 7587281
TI  - Cryopreservation of the common carotid artery of the rabbit: optimization of
      dimethyl sulfoxide concentration and cooling rate.
AB  - This paper describes the continuation of studies that demonstrated the
      suitability of CP-Tes solution as a medium for the introduction and removal of
      dimethyl sulfoxide in rabbit common carotid arteries and established the kinetics
      of cryoprotectant permeation in that tissue. In this paper we report the
      tolerance of rabbit common carotid artery to dimethyl sulfoxide, in
      concentrations up to 30% (w/w), using a technique of exposure that was designed
      to control osmotic stress. The maximum concentration achieved without damage was
      15% (w/w). Vessels were then equilibrated with 15% dimethyl sulfoxide and cooled
      to -80 degrees C at 0.22, 0.69, 2.15, or 9.63 degrees C/min: they were then
      transferred to the gas phase of a liquid nitrogen refrigerator (temperature below
      -160 degrees C) for storage. Thawing was carried out in a 37 degrees C water
      bath. The optimum rate of cooling for these conditions was found to be 0.69
      degrees C/min. The maximal recovery of contractile force in response to 10(-6) M
      norepinephrine was 30-40%; relaxation to acetylcholine (an endothelium-mediated
      function) was 80% of control, and an estimated 71% of endothelial cells survived
      with minimal ultrastructural change.

PMID- 7587283
TI  - Ethylene glycol permeation and toxicity in the rabbit common carotid artery.
AB  - The rate of permeation of ethylene glycol (EG) and the maximum concentration that
      can be tolerated without functional damage was measured in the rabbit common
      carotid artery. Pairs of arteries were perfused on ice, one (the control) with a
      high K+ balanced salt solution containing 100 mM TES (CPTES), and the other with
      ethylene glycol/CPTES solutions. The concentration of EG was increased in a
      stepwise manner in order to reduce osmotically induced changes in endothelial
      cell volume. The final concentration was 10, 20, or 40% EG (w/w). After exposure
      for 20 min, the EG was then removed at room temperature using stepwise decreasing
      concentrations of ethylene glycol in the presence of 3% mannitol. After this, the
      contractile function of the smooth muscle was tested at 37 degrees C with
      noradrenaline and the integrity of the endothelium was assessed structurally by
      vital staining and functionally by its capacity to produce endothelium-derived
      relaxation factor in response to administration of acetylcholine. The tissue
      concentration reached 8.6% after 30 min of exposure to 10% EG. The contractile
      function of the smooth muscle was unaffected by EG at all concentrations. There
      was a significant (50%) reduction in the ACh-induced relaxation of contracted
      arteries after exposure to 40% EG (P < 0.02) but this was not associated with any
      detectable loss of cells or damage to the endothelium. It was concluded that EG
      warrants further investigation as a cryoprotectant for blood vessels.

PMID- 7587282
TI  - Beneficial effect of S-adenosylmethionine during both cold storage and
      cryopreservation of isolated hepatocytes.
AB  - Oxygen free radicals appear to be the prime cell-toxic products during cold
      preservation. Glutathione (GSH) seems to play a critical role in cell protection
      against oxidant stress. The experimental decrease of intracellular GSH in vivo
      may be prevented by the administration of S-adenosylmethionine (SAMe), which
      seems also to play an important role in preserving the structure of cell
      membranes. We designed our study to investigate whether the addition of SAMe to
      EuroCollins solution (EC) could provide a similar degree of protection as the
      more complex University of Wisconsin (UW) solution during cold preservation. In
      addition, we have investigated a possible protective action of SAMe during
      hepatocyte cryopreservation. Wistar rat hepatocytes (10(6) cells/ml) were stored
      in either EC (+/- 12 mumol/l SAMe) or UW. In parallel, hepatocytes (10(6)
      cells/ml) were cryopreserved in M199 culture medium (+/- SAMe) using dimethyl
      sulfoxide as cryoprotectant. LDH release, viability, and hepatocyte GSH and
      malondialdehyde (MDA) content were sequentially determined during cold
      preservation. There were no differences on viability or GSH and MDA content
      between EC+SAMe and UW stored cells, although LDH release was slightly higher in
      the first group. The addition of SAMe also attenuated the decrease in both
      viability (37 +/- 0.8 vs 53.0 +/- 7.4%, mean +/- SEM, N = 5, P < 0.05) and GSH
      content (13.4 +/- 15.1 vs 45.1 +/- 16.8%, mean +/- SEM, N = 5, P < 0.01),
      observed after thawing. Our results suggest that SAMe could be a useful additive
      for both cold storage and cryopreservation solutions of hepatocytes.

PMID- 7587284
TI  - In vitro fertilization and development of immature and mature bovine oocytes
      cryopreserved by ethylene glycol with sucrose.
AB  - Immature and mature bovine oocytes were frozen slowly in 1.8 M ethylene glycol
      (EG) with different concentrations of sucrose (0, 0.1, and 0.2 M). After thawing
      and dilution of the cryoprotectant by a one-step procedure, the survival of the
      oocytes was assessed morphologically and also by in vitro fertilization and
      culture. Sucrose had no effect on the survival and fertilization rates of frozen
      thawed oocytes. However, higher cleavage rates of frozen-thawed immature oocytes
      were obtained with 0.2 M sucrose used in combination with EG. Moreover, none of
      the immature oocytes frozen in EG without sucrose developed into blastocysts, but
      about 1% of immature oocytes frozen with sucrose developed into blastocysts. The
      cleavage rates of mature oocytes frozen in EG were significantly lower with
      sucrose than without sucrose. However, no significant difference was observed in
      the development to blastocysts. Transfer of four blastocysts derived from frozen
      thawed immature oocytes into two recipient heifers resulted in one pregnancy.

PMID- 7587287
TI  - Water permeability and its activation energy for individual hamster pancreatic
      islet cells.
AB  - Coupled with the rapid development of clinical pancreatic islet transplantation,
      there is an increasing requirement for cryopreservation of viable islets.
      Fundamental cryobiology requires determination of several cryobiophysical
      parameters to predict optimal cryopreservation procedures. These include water
      permeability or hydraulic conductivity (Lp) and its activation energy (Ea), the
      permeability of the cell plasma membrane to a cryoprotectant(s) (Ps) and its Ea,
      the osmotically inactive fraction of cell volume (Vb), and the intracellular ice
      formation temperature. For islet cells, these parameters have not previously been
      reported. In the present studies, the Lp, its Ea, and Vb were determined for
      isolated individual golden hamster pancreatic islet cells. The Lp and Vb
      parameters were also measured for corresponding exocrine cells. Both islet and
      the exocrine cells appeared to be ideal osmometers over the experimental range
      when examined by the Boyle Van't-Hoff relationship (linear regression, r = 0.99
      for both types of cells). Extrapolation of these plots generated Vb values of
      0.40 for the islet cells and 0.45 for the pancreatic exocrine cells. To determine
      the Lp, kinetic changes of cell volume over time (dv/dt) in response to
      anisoosmotic conditions (ranging from 145 mOsm/kg to 1.35 Osm/kg) were measured
      using an electronic particle counter. The experimental data were fitted to
      generate the Lp values by least-squares curve fitting to a differential equation
      describing osmotic water movement across the plasma membrane. For pancreatic
      islet cells, the Lp was determined to be 0.25 +/- 0.03 microns/min/atm (mean +/-
      SD, n = 14) at 22 degrees C, 0.54 +/- 0.07 (n = 10), 0.06 +/- 0.008 (n = 9), and
      0.01 +/- 0.001 (n = 9) at 37, 8 and 0 degrees C, respectively. The Ea for Lp was
      calculated from the slope of the Arrhenius plot based upon the mean Lp values at
      the four different temperatures. The Ea was 16.21 Kcal/mol between 0 and 37
      degrees C. Based upon these values, an optimal cooling rate for cryopreserving
      pancreatic islet cells is predicted to be approximately 0.5 degrees C min. The Lp
      for the individual exocrine cells was determined to be 3.73 +/- 1.75
      microns/min/atm (n = 13) at 22 degrees C, which was approximately 10 times the Lp
      value of the corresponding islet cells.

PMID- 7587286
TI  - Effect of different protein supplements on motility and plasma membrane integrity
      of frozen-thawed stallion spermatozoa.
AB  - Three experiments were conducted to evaluate the effect of different
      macromolecule components (egg yolk, skim milk, and BSA) in a widely employed
      extender for cryopreservation of horse semen. Spermatozoal motility (MOT) and the
      percentage of spermatozoa with an intact plasma membrane (IPM) were evaluated in
      frozen-thawed samples. In the first experiment (four Draft Horse stallions, four
      ejaculates each) a standard freezing extender containing 20% whole egg yolk was
      modified by replacing extender components (glucose-EDTA solution, 11% lactose
      solution) with an increasing volume of a skim milk diluent (0, 25, 50, and 75%,
      v/v). The best results were obtained with an extender containing 75% (v/v) skim
      milk solution (MOT 24.7%; IPM 46.6%). This extender was further tested in
      Experiment 2 (three Draft Horse stallions, four ejaculates each) by varying the
      amount of egg yolk (10 or 20%) and by addition of 5% BSA. Neither the amount of
      egg yolk nor the addition of BSA significantly influenced postthaw results.
      Selected extenders from the previous experiments were tested in Experiment 3
      (three stallions, four ejaculates each). Again, a mixture of 20% whole egg yolk
      and a skim milk solution provided the best results (MOT 41.7%; IPM 54.2%). The
      results of this study indicate that the inclusion of different sources of
      macromolecules (e.g., egg yolk and skim milk) can improve motility and plasma
      membrane integrity of frozen-thawed horse spermatozoa.

PMID- 7587289
TI  - Letters across the Atlantic.

PMID- 7587288
TI  - Altruism in hotline volunteers--the final distortions of caring.

PMID- 7587285
TI  - The importance of calcium-related effects on energetics at hypothermia: effects
      of membrane-channel antagonists on energy metabolism of rat liver.
AB  - During normothermic metabolism, the active pumping of Ca2+ across the cell
      membrane, mitochondria, and specialized sequestration organelles accounts for a
      large proportion of total energy expenditure in the cell. This study was designed
      to determine the effects of Ca2+ channel antagonists (chlorpromazine, verapamil,
      nifedipine, prenylamine, and nisoldipine) on energy metabolism and levels of
      glycolytic substrate (glucose) and anaerobic endproduct (lactate) during cold
      ischemia in rat livers. We hypothesized that if the passive channels were blocked
      during cold ischemia, then the ATP requirement of active ion pumping would be
      reduced and ATP levels and energy charge ratios would remain higher throughout
      the ischemic period; thus, viability of the liver would also be increased after
      prolonged ischemia. The most positive effect on energy metabolism was observed in
      the chlorpromazine-treated livers, followed by verapamil treatment. In the
      chlorpromazine treatment, total adenylate (TA) contents were 0.5-1.0 mumol/g (P <
      0.05) higher than the sham group for most of the 24-h time course. Energy charge
      (EC) ratios were 0.05-0.07 higher than the sham values up to 4-10 h ischemia.
      Verapamil treatment was less effective, but still exhibited positive effects on
      TA levels at several time points (20 min, 10 h, and 24 h) throughout the entire
      24-h period. In both of these groups, TA values by 24 h ischemia were similar to
      levels at 10 h in the sham group (3.1 mumol/g), thus showing a considerable
      effect in maintaining adenylate levels. Despite similar pharmacological
      antagonist activities, ATP levels in the nifedipine, prenylamine, and nisoldipine
      treatment groups were 1.0-1.5 mumol/g (P < 0.05) less than the corresponding sham
      group (without Ca2+ antagonists) over the first 1 h ischemia. The decreases in
      high energy adenylate levels were reflected in lower EC ratios in these three
      groups; values were 0.06-0.17 (P < 0.05) lower than corresponding sham values.
      Finally, it was an unexpected finding that the sham injection (0.5 mg/kg
      ethanol+PEG400) resulted in the sustained elevation of ATP, total adenylates, and
      EC values over the first h; EC ratios remained at initial (t = 0) values (EC =
      0.71 +/- 0.01) up to 1 h.

PMID- 7587290
TI  - Nutrition.

PMID- 7587292
TI  - Prison suicide: an overview and guide to prevention (Part 3).

PMID- 7587291
TI  - Suicide attempts in adolescence--"self-report" and "other-report".

PMID- 7587293
TI  - Repeat callers and the Samaritan telephone crisis line--a Canadian experience.
AB  - Telephone crisis lines are increasingly providing a much needed service in the
      community to the lonely, the depressed, and the suicidal. The Samaritan volunteer
      crisis line discussed here is open to any person at any time, day or night. The
      instant availability of such an anonymous service attracts callers who use the
      line inappropriately; these people are often referred to as repeat callers. The
      Samaritans discovered that repeat callers were creating serious problems for both
      staff and volunteers. The difficult task was to develop a policy to restrict the
      repeat callers, but at the same time ensuring that the mandate of the crisis line
      was offered to them. This article examines the characteristics of repeat callers,
      and makes suggestions about the management of the chronic caller.

PMID- 7587294
TI  - Background and introduction to the WHO/EURO Multicentre Study on Parasuicide.
AB  - In most European countries, suicidal behavior is a major public health problem
      and a considerable drain on resources at both the primary and secondary health
      care levels. Unfortunately, due to cross-cultural differences both in medical
      treatment of nonfatal suicidal behavior and in research methodologies, it has
      proved almost impossible to make valid comparisons between countries. It is
      therefore imperative that international studies based on the same definitions and
      methodologies be facilitated if we want to extend our knowledge of suicidal
      behavior and be able to make suggestions for intervention and prevention. The WHO
      Regional Office for Europe decided to support a collaborative multicenter study,
      designed to provide a reliable epidemiological picture of parasuicide in Europe.
      This article provides an introduction to the study.

PMID- 7587295
TI  - Preventing suicide in women and men.
AB  - A review of gender differences in the response to suicide prevention strategies
      suggests that they may be more effective in helping suicidal women than suicidal
      men. More attention needs to be given to the problem of directing these
      strategies to suicidal men.

PMID- 7587296
TI  - Single road traffic deaths--accident or suicide?
AB  - Many authors have suggested that some deaths resulting from road traffic
      accidents are in fact suicide. The purpose of this study was to examine the
      circumstances of single road traffic deaths in County Mayo, Ireland, over the 15
      year period from 1978 to 1992 inclusive. Using the information available from the
      coroners' files, evidence was sought to support the hypothesis that some
      accidental deaths may have been disguised suicides. The authors could find no
      conclusive evidence to suggest that this hypothesis was true. However, there was
      suspicion of suicide in six (4.5%) of the 134 fatalities examined. Interesting
      data regarding gender differences, seasonality, time of accident, and the
      consumption of alcohol were found.

PMID- 7587298
TI  - Atomic force microscopy of the cornea and sclera.
AB  - We report the first investigation of the extracellular matrix of cornea and
      sclera using an atomic force microscope (AFM), and evaluate the potential of this
      new technique. We were able to obtain 2-3 nanometre resolution of both tissues in
      a condition close to their native state. The AFM was able to resolve surface
      features on the collagen fibrils, as well as providing unique images of
      crossbridge structures between collagen fibrils in both cornea and sclera.

PMID- 7587297
TI  - Effects of timolol, terbutaline and forskolin on IOP, aqueous humour formation
      and ciliary cyclic AMP levels in the bovine eye.
AB  - We have studied the effects of terbutaline, timolol, forskolin and 8-bromo cyclic
      AMP on aqueous humour formation, intraocular pressure and on ciliary epithelial
      cyclic AMP levels, either in presence or in absence of IBMX, using the bovine
      isolated arterially perfused eye, excised ciliary processes and cultured ciliary
      epithelium. Both terbutaline, a beta-adrenoceptor agonist, and timolol, a beta
      adrenoceptor antagonist, caused significant reduction in aqueous humour formation
      and intraocular pressure but produced no effect on ciliary epithelial cyclic AMP
      content in the absence of IBMX. Even a three times higher dose of terbutaline was
      entirely ineffective in producing any effect on ciliary cyclic AMP in the
      perfused eye. On the other hand, terbutaline at the IOP-reducing dose, produced a
      significant increase in cyclic AMP when injected after 30 min perfusion with
      IBMX. Incubation of excised ciliary processes or cultured ciliary epithelial
      cells with terbutaline (10(-6) to 10(-4) M) produced concentration-dependent
      increases in cyclic AMP, in both tissues, even in the absence of IBMX. Forskolin,
      which stimulates cyclic AMP synthesis without interacting with cell surface
      receptors, was found to produce highly significant increases in ciliary cyclic
      AMP content both in presence and in absence of IBMX but had no effect on aqueous
      humour formation in the isolated eye. IBMX perfused at concentrations of 1 mM or
      10 microM had no effect on basal levels of ciliary cyclic AMP but the 1 mM
      concentration produced a marked and significant reduction in IOP. Direct
      application of 8-bromo cyclic AMP, a cell permeable analogue, more resistant to
      hydrolysis by phosphodiesterases, had also no effect on aqueous humour formation
      in the perfused eye. It is concluded that in the bovine arterially perfused eye,
      the correlation between the aqueous humour formation rate and ciliary epithelial
      cyclic AMP content is unclear.

PMID- 7587300
TI  - The predicted structure of chick lens CP49 and a variant thereof, CP49ins, the
      first vertebrate cytoplasmic intermediate filament protein with a lamin-like
      insertion in helix 1B.
AB  - The full length cDNA sequence for the lens-specific intermediate filament
      protein, CP49, from chicken is presented. The sequence contains features typical
      of the other intermediate filament proteins, including two major alpha-helical
      regions, helix I and II and appropriate linker regions. CP49 lacks a C-terminal
      non-alpha-helical domain and is only the second intermediate filament protein to
      be described missing this feature. Comparison to the bovine CP49 shows
      significant homology in all domains except the N-terminal non-alpha-helical
      domain. Besides bovine CP49, the other protein most homologous to chicken CP49 in
      the database was keratin 18, a type I keratin. A variant of CP49 is also
      described, called CP49ins. Of the 61 positive clones identified in the library,
      two encoded CP49ins, one of these being a full-length clone. The sequence
      differed to CP49 by the insertion of 49 amino acids in helix IB. This is the
      first chordate cytoplasmic intermediate filament protein sequence to be
      identified with an archetypal lamin-like insertion in this helical subdomain and
      represents a key discovery in tracing the evolutionary pathway of intermediate
      filament protein family.

PMID- 7587299
TI  - Early changes in matrix metalloproteinases and inhibitors after in vitro laser
      treatment to the trabecular meshwork.
AB  - Extracellular matrix turnover in the trabecular meshwork may play a role in
      regulating aqueous humor outflow. Laser trabeculoplasty is a common treatment for
      open-angle glaucoma. The mechanism of this treatment is not understood. We
      investigated changes in the levels and expression of the matrix
      metalloproteinases and their tissue inhibitors (TIMPs) in this tissue using
      cultured human anterior segment explants and standard clinical-parameter laser
      treatment. Medium gelatinase A activity levels are relatively high for sham
      treated controls and are not changed dramatically following laser treatment.
      Medium gelatinase B and stromelysin activity levels are low in sham-treated
      explants and increase significantly by 24 h after treatment. TIMP1 levels, as
      assessed by immunoblots of Western transfers, are initially low. However, by 24 h
      TIMP1 levels have increased significantly. Using semi-quantitative reverse
      transcription and the polymerase chain reaction, mRNA levels of stromelysin,
      gelatinase B and TIMP1 are shown to increase after laser treatment, while
      gelatinase A and TIMP2 remain relatively constant. The increases in trabecular
      stromelysin and gelatinase B in response to laser trabeculoplasty may have
      important implications for the mechanism of action of this treatment for open
      angle glaucoma.

PMID- 7587302
TI  - Effect of carbachol on phospholipase C-mediated phosphatidylinositol 4,5
      bisphosphate hydrolysis, and its modulation by isoproterenol in rabbit corneal
      epithelial cells.
AB  - The effects of carbachol (CCh) on phospholipase C(PLC)-mediated
      phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis and its modulation by
      isoproterenol were investigated in SV40-adenovirus transformed rabbit corneal
      epithelial cells (RCEC). When examined under light microscope, these cells
      exhibited a cobblestone-like appearance typical of the corneal epithelial cells
      grown in primary culture. Addition of CCh (0.1 mM) for 30 min to RCEC, prelabeled
      with 32Pi, decreased the radioactivity in phosphatidylinositol 4-phosphate and
      PIP2 by 15 and 27%, respectively, and concomitantly increased the radioactivity
      in phosphatidylinositol and phosphatidic acid by 14 and 38%, respectively. When
      the concentration of CCh was increased to 1 mM, the changes in radioactivity were
      even more pronounced. Addition of CCh (0.1 mM) to the cells, prelabeled with
      myo[3H]inositol, increased the accumulation of [3H]inositol 1,4,5-trisphosphate
      ([3H]InsP3) by 115%, indicating stimulation of PLC-mediated PIP2 hydrolysis.
      Similar increases were also observed in [3H]InsP1 and [3H]InsP2. The effects of
      CCh on inositol phosphate accumulation were time- and dose-dependent, and were
      inhibited by atropine (10 microM), suggesting that the observed effects of CCh
      were mediated by activation of muscarinic cholinergic receptors. The effects of
      CCh were antagonized more potently by 4-diphenylacetoxy N-methyl-piperidine than
      by pirenzepine, indicating that the muscarinic receptors involved in PLC
      activation are probably of M3 type. By Western immunoblotting analysis with
      various anti-PLC antibodies, the RCEC were shown to contain PLC gamma 1 and PLC
      delta 1 in the soluble fraction and PLC beta 1 in the microsomal fraction.
      Addition of isoproterenol to RCEC, increased cAMP both in a time- and dose
      dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587301
TI  - Vitreous and aqueous humors contain a latent proteinase activity that abolishes
      IGF binding to specific IGF binding proteins.
AB  - Several distinct insulin-like growth factor binding proteins (IGFBPs) are present
      in tissues and fluids of the developing and adult eye. However, the mechanism(s)
      involved in the regulation of ocular IGFBP levels is unknown. We have now
      identified an endogenous factor in vitreous and aqueous humors that, when
      activated by sodium dodecyl sulfate (SDS), abolishes the capacity of specific low
      molecular weight IGFBPs (i.e. 24-30 kDa) to bind IGF as assessed by western
      ligand blotting. In contrast, IGF binding to the 46 and 32 kDa IGFBPs (IGFBP-3
      and IGFBP-2 respectively) is not affected by the SDS-activated inhibitory factor
      (IF). Maximal activation of the IF occurs at an SDS concentration of
      approximately 0.015%. Incubations in the presence of the serine-proteinase
      inhibitor aprotinin result in marked inhibition of IF activity. Preliminary
      characterization by ultrafiltration suggests that the IF is large (< 100 kDa)
      and/or that it is present in a complex. The finding of a factor, most likely a
      serine proteinase, that specifically abolishes IGF binding to low molecular
      weight IGFBPs suggests a mechanism for regulating the levels of these IGFBPs and
      thus the functional activities of IGFs in ocular fluids under normal and/or
      pathological conditions.

PMID- 7587303
TI  - Retinal artery occlusion in rabbit eyes using human atheroma.
AB  - Previous animal models of central retinal artery occlusion using glass or latex
      embolic material may not simulate human disease. We have developed a rabbit model
      using human atherosclerotic material, which may be useful in developing embolus
      specific treatments, including thrombolysis or laser photodisruption. Fresh human
      atherosclerotic plaque was harvested from atherosclerotic human aorta by
      mechanical removal and suspension in normal saline. The suspension was agitated
      vigorously to produce small particles, which were separated into various sizes by
      filtration through mesh filters with specific pore sizes. The common carotid
      artery of the anesthetized rabbit was isolated by neck dissection and cannulated
      using a modified Seldinger technique. Suspensions of human atherosclerotic plaque
      were injected into the common carotid artery via this cannula. All animals were
      examined by slit lamp and fluorescein angiography before and after retinal artery
      occlusion. This model reliably produced retinal artery occlusion using human
      atherosclerotic plaque. Plaque particles less than 105 microns reliably produced
      branch retinal artery occlusion, while larger plaque particles less than 149
      microns reliably produced central retinal artery occlusion. Sublingual
      nitroglycerin, at 0.1 mg/kg, intravenous verapamil, from 0.2 mg/kg to 2 mg/kg,
      and intracarotid urokinase given acutely in standard doses failed to cause
      reperfusion. This model will be very useful in the study and treatment of retinal
      vascular disorders as it may more closely simulate human disease over previous
      models using artificial embolic materials. Embolic specific treatment stategies,
      such as thrombolysis and laser photodisruption, may be further developed with
      this model.

PMID- 7587304
TI  - Study of lymphocyte dynamics in the ocular circulation: technique of labeling
      cells.
AB  - The purpose of this experiment was to study in vivo the dynamic behavior of the
      lymphocyte in the retinal circulation. We developed a new technique capable of
      visualization of lymphocyte motion in the retinal and choroidal vessels using a
      rat model. Live cells freshly removed on a donor animal were labeled by a simple
      method using fluorescein isothiocyanate. Labeled cells were injected systemically
      into another animal. Retinal images were reconstituted on a video screen with a
      scanning laser ophthalmoscope (SLO) utilizing the argon green laser excitation
      wavelength (514.5 nm) to detect cell fluorescence. Lymphocytes were clearly seen
      and followed in the retinal vessels. Some slowed down in the capillary system, or
      even stopped for a few seconds, or were definitively caught in it. Labeled cells
      remained visible after circulating several times. A method was developed for in
      vivo visualization of lymphocytes in the retinal circulation. This method has the
      potential for application in the study of lymphocyte cell behavior under
      physiological as well as pathological conditions.

PMID- 7587305
TI  - The effects of bFGF on RCS rat eyes.
AB  - Basic fibroblast growth factor (bFGF) has been implicated as a factor in retinal
      differentiation and disease. Recent studies have shown that subretinal or
      intravitreal injections of bFGF delay the retinal degeneration of the RCS rat but
      the global nature of this effect has been quantified for few test animals and the
      mechanism underlying this effect is not understood. In order to determine more
      accurately the global effects of intravitreal bFGF and to further elucidate the
      mechanism of bFGF promoted photoreceptor cell saving, we injected one of three
      bFGF doses into the vitreal cavities of young RCS rats. Using measurements from
      several eyes, we confirmed that a single intravitreal bFGF injection globally
      delays the RCS dystrophy. Test eyes contained fewer debris zone macrophages and
      more inner retinal macrophages than did control eyes at 1 month post injection.
      As bFGF's saving effect waned, the number of inner retinal macrophages decreased
      and the number of debris zone macrophages increased toward control levels. Dose
      dependent cataract formation occurred in 100% of test eyes. Eyes that received
      the highest bFGF dose showed increased retinal vascularization at 1, 2 and 3
      months post injection. The possible relationships between bFGF promoted
      photoreceptor survival and our findings are discussed.

PMID- 7587306
TI  - Evaluation of albumin concentration in rabbit anterior chamber with laser flare
      cell meter.
AB  - To find an appropriate way of using Kowa's laser flare-cell meter in evaluating
      the anterior chamber albumin concentration, we characterized the relationship
      among the flare intensity determined with the flare-cell meter in terms of photon
      count/ms (flare value), flare value converted to albumin concentration, and
      anterior chamber albumin concentration in drug-treated rabbit eyes. Flare
      measurement was done in rabbits that received intravenous administration of
      fluorescein isothiocyanate-labeled albumin and instillation of prostaglandin E1,
      pilocarpine, or tropicamide. Flare value, anterior chamber fluorescence, plasma
      fluorescence, and plasma albumin concentration were determined. Anterior chamber
      albumin concentration was calculated from the plasma albumin concentration and
      the corrected aqueous/plasma fluorescence ratio. The correlation between the
      flare value converted to albumin concentration (Albequiv) and the anterior
      chamber albumin concentration (Albac) had two phases: 1) Linear correlation was
      found when the flare value was below 100 photon count/ms: Albac = 0.53 Albequiv -
      0.006, r = 0.98; 2) When the flare value was above 100 photon count/ms, the
      correlation was lower and had a different slope. In this condition, the Albac was
      correlated better with the flare value itself: Albac = 0.0042 [flare value] +
      0.17, r = 0.88. The results suggested that anterior chamber albumin concentration
      is evaluated quantitatively from the converted flare value when the flare value
      is below 100 photon count/ms and from the flare value itself when the flare value
      is above that level.

PMID- 7587307
TI  - EGF and PGE2: effects on corneal endothelial cell migration and monolayer
      spreading during wound repair in vitro.
AB  - In vivo repair of the adult human corneal endothelium occurs mainly by movement
      of cells into the wound defect rather than by cell division. Two forms of cell
      movement contribute to endothelial wound repair: migration of individual cells
      into the defect and spreading of the confluent monolayer into the wound area.
      This laboratory has developed a tissue culture model using rabbit corneal
      endothelial cells pretreated with the mitotic inhibitor 5-fluorouracil to mimic
      the relatively amitotic state of human corneal endothelium in vivo. This model
      permits study of the effects of growth factors and other agents on individual
      cell migration and monolayer spreading in response to wounding. mRNA for
      epidermal growth factor (EGF) and its receptor has been detected in cultured
      corneal endothelial cells and EGF receptors have been detected on human corneal
      endothelial cells in situ, suggesting that this growth factor may act in an
      autocrine manner. Prostaglandin E2 (PGE2) is synthesized by cultured corneal
      endothelial cells and is present in relatively high quantity in aqueous humor in
      response to corneal wounding and to inflammation in the anterior chamber.
      Although corneal endothelial cells may be exposed to both EGF and PGE2, little is
      known about their effects on monolayer repair. The current study compared the
      effects of PGE2 alone, EGF alone, and both agents in combination on individual
      cell migration and monolayer spreading using the wound model system and also
      determined the effect of EGF on PGE2 secretion using a commercial immunoassay. A
      15 min exposure of wounded cultures to exogenous PGE2 stimulated individual cell
      migration and suppressed monolayer spreading.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587309
TI  - Exogenous dermatology. Advances in skin-related allergology, bioengineering,
      pharmacology, and toxicology. Festschrift in honor of Howard I. Maibach on his
      65th birthday.

PMID- 7587308
TI  - Isolation and culture of human trabecular meshwork cells by extracellular matrix
      digestion.
AB  - Like corneal endothelial cells, human trabecular meshwork cells are believed to
      be of neural crest origin, but demonstrate physiological properties and an
      antithrombogenic surface similar to vascular endothelial cells. One current
      method for isolating trabecular meshwork cells utilizes the motile nature of
      these cells to migrate away from a trabecular meshwork explant in culture to more
      distal regions of the culture dish. This 'outgrowth' technique is limited in
      practice by the relatively small number of cells that migrate per explant per
      unit time, thus hindering the ability to gather sufficient numbers of cells for
      comprehensive experimentation. For this reason, we have modified an extracellular
      matrix digestion technique in current use for the isolation of microvascular
      endothelial cells to isolate human trabecular meshwork cells. This procedure is
      both efficient and rapid for isolating large numbers of trabecular meshwork cells
      and results in the availability of trabecular meshwork cells in sufficient
      quantities for subsequent experimentation.

PMID- 7587311
TI  - Scabies: what's new?

PMID- 7587310
TI  - The allergen bank: the idea behind it and the preliminary results with it.

PMID- 7587313
TI  - Four decades of topical corticosteroid assessment.

PMID- 7587312
TI  - Twenty absorbing years.

PMID- 7587315
TI  - Correlation of in vivo and in vitro percutaneous absorption with a mathematical
      model.

PMID- 7587314
TI  - Percutaneous absorption: physical chemistry meets the skin.

PMID- 7587316
TI  - Prediction of drug concentration in blood after topical application.

PMID- 7587317
TI  - Challenges in evaluating bioequivalence of dermatological drug products.

PMID- 7587318
TI  - Adsorption columns in in vitro percutaneous absorption studies: a novel approach
      for dermatopharmacokinetics.

PMID- 7587319
TI  - Polar pathway for percutaneous absorption.

PMID- 7587320
TI  - Immediate contact reactions.

PMID- 7587321
TI  - Effects of multilamellar vesicles on the disruption of stratum corneum lipids
      barrier in hairless mice.

PMID- 7587322
TI  - Transdermal iontophoresis: effect of penetration enhancer and iontophoresis on
      drug transport and surface characteristics of human epidermis.

PMID- 7587323
TI  - Facilitated drug delivery during transdermal iontophoresis.

PMID- 7587325
TI  - Percutaneous absorption of a drug into hair follicles.

PMID- 7587326
TI  - Cutaneous metabolism and penetration of methoxypsoralen, betamethasone 17
      valerate, retinoic acid, nitroglycerin and theophylline.

PMID- 7587327
TI  - Examples of the use of cell cultures in skin irritancy assessment.

PMID- 7587324
TI  - Assessment of delipidization as an enhancing factor in percutaneous penetration.

PMID- 7587328
TI  - In vitro skin irritancy: application of keratinocytes cell culture and its
      correlation with human patch test responses.

PMID- 7587329
TI  - Clinical standardization of the TRUE Test formaldehyde patch.

PMID- 7587330
TI  - Lymphocyte transformation test in the diagnosis of immediate type
      hypersensitivity reactions to penicillins.

PMID- 7587331
TI  - Contact allergy: animal models.

PMID- 7587334
TI  - Quantification of biophysical properties of the skin.

PMID- 7587333
TI  - Immunomodulation of contact dermatitis.

PMID- 7587332
TI  - UV-dependent local lymph node reactions: photoallergy and phototoxicity testing.

PMID- 7587335
TI  - Regional variations of human skin blood flow response to histamine.

PMID- 7587336
TI  - Irritancy exposure assessment in metal workers.

PMID- 7587337
TI  - Effects of surfactants on skin hydration.

PMID- 7587338
TI  - Textile dye contact allergens.

PMID- 7587339
TI  - Occupational skin disease.

PMID- 7587341
TI  - Antibiotic resistance in acne patients under antibiotic treatment in comparison
      to an untreated control group with retrospective assessment of therapy.

PMID- 7587340
TI  - Acute irritant dermatitis: effect of short-term topical corticoid treatment.

PMID- 7587342
TI  - Perioral dermatitis.

PMID- 7587343
TI  - Coronary risk factors and their modification: lipids, smoking, hypertension,
      estrogen, and the elderly.

PMID- 7587344
TI  - Hemorrhagic shock.
AB  - A great deal has been learned about the pathophysiologic condition of hemorrhagic
      shock. The response of the hormonal and inflammatory mediator systems in patients
      in hemorrhagic shock appears to represent a distinct set of responses different
      from those of other forms of shock. The classic neuroendocrine response to
      hemorrhage attempts to maintain perfusion to the heart and brain, often at the
      expense of other organ systems. This intense vasoconstriction occurs via central
      mechanisms. The response of the peripheral microcirculation is driven by local
      tissue hypoperfusion that results in vasodilation in the ischemic tissue bed.
      Activation of the systemic inflammatory response by hemorrhage and tissue injury
      is an important component of the pathophysiologic condition of hemorrhagic shock.
      Activators of this systemic inflammatory response include ischemia/reperfusion
      injury and neutrophil activation. Capillary "no-flow" with prolonged ischemia and
      "no-reflow" with reperfusion may initiate neutrophil activation in patients in
      hemorrhagic shock. The mechanisms that lead to decompensated and irreversible
      hemorrhagic shock include (1) "arteriolar hyposensitivity" as manifested by
      progressive arteriolar vasodilation and decreased responsiveness of the
      microcirculation to alpha-agonists, and (2) cellular injury and activation of
      both proinflammatory and counterinflammatory mechanisms. These changes represent
      a failure of the microcirculation. Redistribution of cardiac output and
      persistent gut ischemia after adequate resuscitation may also contribute to the
      development of irreversible hemorrhagic shock. Treatment of hemorrhagic shock
      includes rapid operative resuscitation to limit activation of the mediator
      systems and abort the microcirculatory changes that result from hemorrhagic
      shock. Volume resuscitation and control of hemorrhage, should occur
      simultaneously. The end point in volume resuscitation of hemorrhagic shock must
      be maintenance of organ system and cellular function. Whether we use adequate
      urine output, correction of lactic acidemia, optimization of oxygen delivery, or
      oxygen consumption as our specific goal, the general objective is to provide
      adequate crystalloid solution and packed red blood cells to achieve and maintain
      normal organ and cellular perfusion and function.

PMID- 7587345
TI  - A theory of follicular dendritic cell origin.

PMID- 7587347
TI  - Follicular dendritic cells: structure as related to function.

PMID- 7587346
TI  - Regulation of human B cell activation by follicular dendritic cell and T cell
      signals.

PMID- 7587349
TI  - Follicular dendritic cells: origin and function.

PMID- 7587350
TI  - Follicular dendritic cells and infection by human immunodeficiency virus type 1-
      a crucial target cell and virus reservoir.

PMID- 7587351
TI  - Follicular dendritic cells in malignant lymphomas.

PMID- 7587348
TI  - Follicular dendritic cells initiate and maintain infection of the germinal
      centers by human immunodeficiency virus.

PMID- 7587352
TI  - Mechanism of immune complex trapping by follicular dendritic cells.

PMID- 7587353
TI  - Follicular dendritic cells: antigen retention, B cell activation, and cytokine
      production.

PMID- 7587354
TI  - Role of follicular dendritic cells in the regulation of B cell proliferation.

PMID- 7587355
TI  - Murine follicular dendritic cells: accessory activities in vitro.

PMID- 7587356
TI  - HIV and dementia. Proceedings of the NIMH-sponsored conference "Pathogenesis of
      HIV Infection of the Brain: Impact on Function and Behavior". April 4-7, 1994,
      Chantilly, Virginia.

PMID- 7587358
TI  - Neurocognitive disorders in HIV-1 infection. HNRC Group. HIV Neurobehavioral
      Research Center.

PMID- 7587357
TI  - Role for astrocytosis in HIV-1-associated dementia.

PMID- 7587361
TI  - Selected models of HIV-induced neurological disease.

PMID- 7587360
TI  - Neurobiology of simian and feline immunodeficiency virus infections.

PMID- 7587359
TI  - Therapeutic approaches to HIV infection based on virus structure and the host
      pathogen interaction.
AB  - The HIV-1 infection of central nervous system, with attendant neuropathy and
      dementia, poses a unique challenge for antiviral therapy. For practical
      considerations, it is important to define carefully the precise therapeutic
      objectives. (1) Is it necessary to inhibit spreading HIV-1 infection in the
      central nervous system? (2) What is the role of inflammatory responses in central
      nervous system disease during HIV-1 infection? (3) Is there a correlation between
      pathology and dementia? (4) Are virions or virus gene products toxic in the
      central nervous system? (5) Is there a role for immune suppression and
      opportunistic pathogens in AIDS dementia? The development of therapeutic agents
      for HIV-1 infection is guided by our knowledge of virus structure, the function
      of viral proteins, the interactions with host components, and detailed features
      of the virus life cycle. In each case, unique features of the virus can be
      identified and established as targets for unique antiviral compounds. Drugs
      acting as inhibitors of virus enzymatic functions are plagued by the rapid
      development in vivo of drug-resistant virus variants, although combination or
      alternating chemotherapeutic regimens may obviate some of these concerns. Novel
      approaches to inhibiting virus are flourishing. In vitro studies show the value
      of agents as diverse as molecular decoys for tat activity to efforts to
      mutagenize integrated proviruses by modified oligonucleotides that form triple
      helices with chromosomal genes. As each particular clinical situation is better
      defined, the design and application of these agents can be refined to inhibit HIV
      1 replication and reduce the associated morbidity.

PMID- 7587362
TI  - Feline immunodeficiency virus as a model for study of lentivirus infection of the
      central nervous system.
AB  - Feline immunodeficiency virus infects the CNS and results in predictable
      pathophysiology strikingly similar to that seen with HIV-1 infection of humans.
      The observed pathophysiology is mimicked in several physiologically assessed
      modalities, further supporting the validity of the feline model. Peripheral and
      control evoked potential findings and the occurrence of the sleep architecture
      changes in both cat and human disease provide an intriguing focus for further
      investigation. Although structurally diverse in an absolute sense, FIV and HIV-1
      share basic structural features and commonalities of their life cycle. It is
      likely that by understanding the common mechanisms by which these lentiviruses
      influence CNS function, a more complete understanding of the neurological
      deficits seen in HIV-1 infected patients will be obtained. The cat model is
      particularly valuable for study of CNS disease, since it allows detailed analyses
      of events during the acute phase of infection, under circumstances in which the
      nature and timing of the infection are carefully controlled. The availability of
      molecular clones for mutational analysis will facilitate mapping of genomic
      regions critical to the perturbation of CNS function. It is suggested that
      development of intervention strategies in the cat model will yield treatment
      modalities directly applicable to HIV-1 infection of humans.

PMID- 7587363
TI  - Transgenic models to assess the neuropathogenic potential of HIV-1 proteins and
      cytokines.

PMID- 7587365
TI  - Traffic of hematogenous cells through the central nervous system.

PMID- 7587364
TI  - Virus entry and release in polarized epithelial cells.

PMID- 7587368
TI  - The pathogenesis of HIV infections of the brain.

PMID- 7587366
TI  - Principles of cytotoxic T lymphocyte induction and recognition.

PMID- 7587367
TI  - Virus-neuron-cytotoxic T lymphocyte interactions.

PMID- 7587369
TI  - AIDS dementia complex and HIV-1 brain infection: a pathogenetic framework for
      treatment and evaluation.

PMID- 7587371
TI  - Penetration of solutes, viruses, and cells across the blood-brain barrier.
AB  - The aspects presented here of how solutes, viruses and cells are able to cross
      the BBB indicate that there must be an active interaction of endothelium with
      viruses and immune system cells before they can penetrate the brain and spinal
      cord. The axoplasmic pathway taken by lectin-solute conjugates is similar but not
      identical to that followed by viral particles during their retrograde or
      anterograde transit through the axoplasm. Both the conjugates and virus are
      transferred to other neurons transsynaptically but the receptor mediated transfer
      utilized by viruses is far more specific. Cranial nerves are involved in both the
      entry and egress of antigens into and out of the brain. Antigen, generated within
      the CNS, may be able to escape from the brain to lymphoid tissue by passing into
      the fluid around a cranial nerve, thence via the lymph into lymph nodes to
      initiate an immune response involving the CNS.

PMID- 7587370
TI  - Quantitative neuropathologic assessment of HIV-1 encephalitis.

PMID- 7587372
TI  - Cytotoxic T lymphocytes and HIV-1 related neurologic disorders.
AB  - In summary, one can conclude that infected persons exhibit an extremely vigorous,
      virus-specific CTL response, and in at least some individuals this response is
      broadly directed at multiple epitopes. These cells are present at the time or
      initial control of viremia and can also be detected after more than a decade of
      asymptomatic infection. These cells can also be found in the central nervous
      system in persons with ADC, and one can envision pathways in which the
      inflammatory cytokines released by these cells upon activation could contribute
      to the neurologic sequelae of infection. However, the precise role of these cells
      as a protective host defense and the possible contribution of these cells, or
      products released by these cells, to tissue damage at sites such as the lung and
      brain remain to be determined. Further delineation of the role played by CTLs in
      the pathogenesis of disease should be extremely useful in helping to understand
      the disease itself and to guide intervention strategies.

PMID- 7587374
TI  - Rat glioma cell line as a model for astrogliosis.
AB  - In this investigation 9L rat glioma cells were grown on coverslips in culture,
      and when subjected to mechanical trauma, they were capable of mounting an
      astroglial response, without interaction with neurons, as evidenced by cell
      hypertrophy and increased immunostaining for glial fibrillary acidic protein and
      J1-31 antigen. It is of particular interest that this neoplastically transformed
      cell line is capable of mounting an astroglial response when subjected to
      mechanical trauma in vitro. The advantages of this model over in vivo models of
      central nervous system injury include the ease of reproducibility of results, and
      the ability to investigate molecular mechanisms under controlled conditions.

PMID- 7587373
TI  - Distinct HIV-1 env sequences are associated with neurotropism and neurovirulence.

PMID- 7587375
TI  - Detection of genomic variability among isolates of Campylobacter jejuni from
      chickens by crossed-field gel electrophoresis.
AB  - Digestion with Sal I facilitated the subclassification of 41 strains of
      Campylobacter jejuni into seven types, and digestion with Sma I enabled
      subclassification into twelve types. Sma I was potentially more useful for the
      detection of variability among the 41 strains, but both restriction enzymes
      seemed to be potentially useful for detecting variability among crossed-field gel
      electrophoresis profiles of the strains. The results clearly demonstrated that C.
      jejuni strains from different sources and with different routes of transmission
      had invaded the three farms investigated. At farms Sa and Ai, approximately 70%
      (23 strains) of isolates of C. jejuni (33 strains) were subclassified into the
      two major genotypes (I and II) on the basis of cleavage profiles with both Sal I
      and Sma I. These two major genotypes appeared to have invaded, expanded in and
      occupied the two chicken farms. All nine strains from farm Ai belonged genotype
      I.

PMID- 7587376
TI  - A novel intermediate filament-associated protein: further characterization of the
      G.3.5 antigen.
AB  - Several novel intermediate filament-associated proteins (IFAPs) have been
      discovered using hybridoma technology on multiple sclerosis plaque tissue. One of
      these, designated the G.3.5 antigen, is a desmin-binding IFAP in skeletal and
      cardiac muscle. It has been suggested that because of sequence similarities to
      alpha-actinin the G.3.5 antigen is an alpha-actinin-like protein which may cross
      link actin and intermediate filaments in the cytoskeleton. In this study, it is
      reported that (1) the G.3.5 antigen is present in hepatocytes in addition to the
      previously described astrocytes, skeletal and cardiac myocytes, fibroblasts, and
      several other non-nervous tissues; (2) in myocytes and hepatocytes, the G.3.5 and
      alpha-actinins do not co-localize; (3) by transmission electron microscopy the
      G.3.5 antigen appears to be a rod-shaped dimer similar to alpha-actinin; (4)
      isolation of the G.3.5 antigen does not simultaneously isolate alpha-actinin; and
      (5) limited proteolysis of the G.3.5 antigen and alpha-actinin generates
      dissimilar maps. In binding studies, alpha-actinin cross-links actin but has no
      effect on desmin; the G.3.5 antigen does not appear to cross-link actin, desmin
      or mixtures of both under the assay conditions. These results support the
      hypothesis that the G.3.5 antigen is a novel IFAP related to alpha-actinin, but
      do not support a role for the antigen as a cross-linker between intermediate
      filaments and actin.

PMID- 7587377
TI  - Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization.

PMID- 7587378
TI  - Assignment of the gene SLC1A2 coding for the human glutamate transporter EAAT2 to
      human chromosome 11 bands p13-p12.

PMID- 7587379
TI  - Physical evidence for the position of the Friedreich's ataxia locus FRDA proximal
      to D9S5.
AB  - Orientation of the Friedreich's ataxia locus (FRDA) with respect to D9S15 and
      D9S5 has proved critical to the design of subsequent cloning strategies. The
      rarity of recombination events between FRDA and these markers, originally used to
      determine assignment to human chromosome region 9q13-->q21.1, has necessitated
      the instigation of physical mapping studies to determine order and, hence, the
      precise location of the disease gene. Simultaneous fluorescence in situ
      hybridisation using cosmid clones located in close proximity to the ends of a 1.2
      Mb yeast artificial chromosome clone extending into the FRDA candidate region
      provides physical evidence for the order of the marker loci to be cen-D9S202-D9S5
      D9S15-qter. The possibility that a pericentric inversion, occurring naturally in
      approximately 1% of the normal population, may affect the order of markers within
      this region has been eliminated. Considered in association with the
      interpretation of a recombination event detected in a single affected individual,
      these data indicate that the FRDA locus is located proximal to D9S5.

PMID- 7587381
TI  - Eight new polymorphic microsatellites in mouse gene loci.
AB  - Eight mouse gene loci (Atp1b2, Epo, Kit, Krt2, Mor1, Ren1, Pdgfb, and Wnt1) that
      contain unidentified microsatellites were selected to detect simple sequence
      length polymorphisms on genomic DNAs from two laboratory strains (C57BL/6J and
      RF/J) and strains recently derived from the Mus musculus species complex
      (CAST/Ei, MOLF/Ei, CZECH II, and M. m. domesticus) and from M. spretus
      (SPRET/Ei). All microsatellite DNA sequences varied in size among some of the
      seven mouse strains tested. These new polymorphisms might be useful in the search
      for tumor suppressor genes involved in specific cancers.

PMID- 7587382
TI  - Localization of IGF1R and EDN genes to pig chromosomes 1 and 7 by in situ
      hybridization.
AB  - The genes coding for the insulin-like growth factor-1 receptor (IGF1R) and a
      porcine endothelium-derived 21-residue vasoconstrictor peptide (EDN) were
      localized in the pig by means of radioactive in situ hybridization. IGF1R was
      mapped to chromosome region 1q1.7-->q2.1 and EDN to 7p1.3-->p1.2. The results are
      discussed in relation to the position of their homologous loci in man.

PMID- 7587383
TI  - NOR and heterochromatin analysis in two cartilaginous fishes by C-, Ag- and RE
      (restriction endonuclease)-banding.
AB  - Selachian chromosomes were investigated for the first time by C-, Ag- and RE
      (restriction endonuclease)-banding. A pair of NOR-bearing acrocentric
      chromosomes, as well as a third extra site, were demonstrated in two species of
      Torpedo. In situ digestion with restriction endonucleases revealed a peculiar
      arrangement of constitutive heterochromatin: in Torpedo ocellata the centromere
      never appeared C-banded, and was always digested by AluI, PstI, DdeI and HaeIII;
      in Torpedo marmorata, instead, heterochromatin was present in the centromere, and
      was not digested by the same enzymes. The occurrence of different types of
      centromeric heterochromatin suggests an involvement of highly repeated DNA
      fractions in the Robertsonian phenomena that occurred in chromosome
      rearrangements in the genus Torpedo.

PMID- 7587380
TI  - Multicolor FISH with a telomere repeat and Sry sequences shows that Sxr (Sex
      reversal) in the mouse is a new type of chromosome rearrangement.
AB  - XYSxr (Sex reversal) mice carry a Y chromosome in which the chromatin (including
      Sry, the gene for testis determination) that normally resides on the short arm is
      duplicated and the second copy is relocated to the distal end of the long arm.
      Multicolor in situ hybridization to mitotic chromosomes of XYSxr males using
      probes for the telomere repeat sequence (TTAGGG)n and Sry shows that the
      rearranged chromatin is located distal to the telomeric signal. This suggests
      that the rearrangement arose from a recombination event involving the distal Y
      telomere sequences, i.e., within the telomere, a structure historically assumed
      to be incapable of participating in chromosome rearrangements.

PMID- 7587384
TI  - Genetic and radiation-reduced somatic cell hybrid sublocalization of the human
      GSTP1 gene.
AB  - A number of related enzymes like glutathione S-transferases (GSTs) and fatty acid
      ethyl ester synthases (FAEESs) have been implicated in detoxification and drug
      resistance. The anionic class of GSTs, pi, and closely related FAEES-III exhibit
      tissue-specific and developmentally regulated expression, and the former has been
      shown to be overexpressed or amplified in a variety of tumors. The GSTP1 gene has
      previously been cloned and cytogenetically localized to human 11q13 by in situ
      hybridization. Using a series of previously described radiation-reduced somatic
      cell hybrids, we have sublocalized GSTP1 to 11q13. We isolated a genomic clone
      containing the entire GSTP1 gene and sequenced it. Analysis of the 5'region
      revealed 23 (TAAAA) tandem repeats interrupted by a single TA and TAA insertion.
      This repeat number differs among individuals. Eleven alleles in a mostly
      Caucasian sample were observed. This repeat has a polymorphism information
      content of 0.74. Linkage analysis of the Venezuelan reference pedigree places
      GSTP1 5 cM distal to PYGM and 4 cM proximal to FGF3 thereby providing a genetic
      marker half-way between these two loci. The sublocalization and genetic
      characterization of GSTP1 facilitates linkage analysis of several disease genes
      mapped to this chromosome band as well as the correlation of genetic and physical
      markers in the region.

PMID- 7587386
TI  - Mapping of the immune interferon gamma gene (IFNG) to chromosome band 12q14 by
      fluorescence in situ hybridization.
AB  - The human immune interferon gamma gene (IFNG) was localized to chromosome band
      12q14 by fluorescence in situ hybridization. This correction of a previous
      localization resolves the discrepancy between the syntenic maps of human
      chromosome 12 and mouse chromosome 10 and facilitates linkage analysis and
      identification of gene interactions near this region of chromosome 12 as well as
      further genetic studies of interferon-gamma immune-associated diseases.

PMID- 7587385
TI  - Meiotic segregation in males heterozygote for reciprocal translocations: analysis
      of sperm nuclei by two and three colour fluorescence in situ hybridization.
AB  - The meiotic segregation of chromosomes was analysed in three reciprocal
      translocation carriers, using FISH on interphase spermatozoa. The segregation
      pattern was first studied in 27,844 spermatozoa from two siblings carrying the
      reciprocal translocation t(6;11)(q14;p14). Three centromeric probes, specific for
      chromosomes 6, 11 and 1, were simultaneously hybridized so that all centric
      fragments as well as the ploidy of each cell could be determined by three colour
      FISH. For both subjects, the respective frequencies of alternate/adjacent 1,
      adjacent 2, 3:1 and 4:0 segregation modes were 88%, 9%, 3+ and < 1%. In another
      reciprocal translocation t(2;14)(p23.1;q31), a two colour FISH analysis was
      performed on 4,610 spermatozoa, using a chromosome 2 centromeric probe and a YAC
      probe located on the centric fragment of chromosome 14. Frequencies of
      alternate/adjacent 1, adjacent 2, and 3:1 segregations were 89%, 5.2%, and 5.8%
      respectively. The segregation of chromosomes X, Y and 1 were also analyzed with
      three colour FISH on the spermatozoa from all three translocation carriers, in
      order to detect an interchromosomal effect. Aneuploidy rates for the X and Y
      chromosomes were found to be in the same range in the three translocation
      carriers and control donors, but disomy 1 rates were slightly increased in the
      translocation carriers.

PMID- 7587387
TI  - Assignment of the uteroferrin gene (ACP5) to swine chromosome 2q12-->q21 by
      fluorescence in situ hybridization.
AB  - A cosmid clone containing the uteroferrin gene (ACP5) was selected from a cosmid
      library of swine genomic fragments by colony hybridization using uteroferrin cDNA
      as a probe. The genomic fragment thus cloned was examined by Southern blot and
      sequence analysis which demonstrated that it contained at least a part of the
      uteroferrin gene. The cosmid clone DNA was labeled with biotin, and used a probe
      for in situ hybridization to swine chromosomes. Hybridization was visualized by
      the FITC-labeled streptavidin/biotinylated antistreptavidin system together with
      R-banding of chromosomes. The hybridization signals revealed that the uteroferrin
      gene (ACP5) is located on swine chromosome 2q12-->q21.

PMID- 7587389
TI  - Assignment of the mouse homologue of a human MEN1 candidate gene, phospholipase C
      beta 3 (Plcb3), to chromosome region 19B by FISH.
AB  - A recent study using comparative mapping analysis suggests that the proximal
      segment of mouse chromosome 19 contains the mouse homologs of the human multiple
      endocrine neoplasia type 1 (MEN1) flanking markers proximal to the locus. We have
      recently shown that phospholipase C-beta 3 (PLCB3) is a candidate gene for the
      MEN1 syndrome. In the present investigation we used fluorescence in situ
      hybridization with a genomic DNA clone for mouse Plcb3, and mapped the locus to
      chromosome region 19B. This is in agreement with the comparative mapping of the
      MEN1 flanking markers in mouse.

PMID- 7587388
TI  - Colocalization of the rat homolog of the von Hippel Lindau (Vhl) gene and the
      plasma membrane Ca++ transporting ATPase isoform 2 (Atp2b2) gene to rat
      chromosome bands 4q41.3-->42.1.
AB  - Using fluorescence in situ hybridization, we localized the rat homolog of the von
      Hippel-Lindau gene (Vhl) to rat chromosome band 4q41.3-->q42.1. We also mapped
      the gene encoding the plasma membrane Ca(++)-transporting ATPase isoform
      2(Atp2b2) to the same chromosome subregion. These two genes together with Raf1
      appear to be members of a large syntenic gene cluster that maps to human
      chromosome bands 3p25-->p26, mouse chromosome bands 6 C3-->E, and rat chromosome
      bands 4q41-->q42. Cytogenetic analysis of NRK 52E cells derived from immortalized
      normal rat kidney epithelial cells revealed an inverted duplication of the region
      containing this gene cluster.

PMID- 7587390
TI  - Two-dimensional DNA typing as a genetic marker system in humans.
AB  - By two-dimensional (2-D) DNA typing several hundred genomic loci can be analysed
      simultaneously in a two-dimensional pattern as spots detected by micro- or
      minisatellite core probes. Many of these loci display DNA sequence polymorphisms,
      and we have examined whether it is possible to extract genetic information from
      the rather complex but potentially very informative 2-D DNA typing patterns. To
      do so, the segregation of 9 spots detected by the microsatellite core probe
      (CAC)n was followed in a large CEPH pedigree, and by linkage analysis it was
      possible to obtain chromosomal assignments of the corresponding (CAC)n loci in
      all cases except one. Furthermore, a regional, physical localization of these
      loci emerged from analysis of the existing genetic and physical localization data
      of DNA markers flanking the (CAC)n loci. We have hereby obtained evidence that
      the spots detected by the microsatellite core probe (CAC)n segregate in a
      Mendelian manner and that it is possible to reliably score the segregation of
      single spots within a family. These results indicate that the large amount of
      potential information inherent in 2-D DNA typing may be used as a genetic marker
      system; an important prerequisite for its application as a genome scanning
      method, e.g. in detection of genomic alterations in cancer and in mapping of
      genetic traits.

PMID- 7587391
TI  - Physical and linkage mapping of human carbamyl phosphate synthetase I (CPS1) and
      reassignment from 2p to 2q35.
AB  - Carbamyl Phosphate Synthetase I (CPS1) (EC 6.3.4.16) is a highly conserved
      mitochondrial enzyme catalyzing the first committed step of waste nitrogen
      metabolism in the urea cycle. Using FISH for physical mapping and CEPH families
      for linkage analysis, we mapped the CPS1 gene (CPS1) to 2q34-->q35, reassigning
      it from 2p where it was originally mapped.

PMID- 7587392
TI  - A physical map of the region spanning the chromosome 12 translocation breakpoint
      in a mesothelioma with a t(X;12)(q22;p13).
AB  - We have constructed a physical map of a 4.6-cM region of human chromosome band
      12p13.3 that contains a translocation breakpoint from a mesothelioma with a
      t(X;12)(q22;p13). The map contains a contig of 22 yeast artificial chromosomes
      (YACs), onto which we have placed 18 sequence tagged site (STS) markers,
      including seven genes: D12S370, FGF6, KCAN1, KCNA5, KCNA6, NTF3, and VWF. A
      second YAC contig, comprised of 22 YAC clones, was located distal to the
      mesothelioma breakpoint and contained 12 STS markers, including four genes
      (CACNL1A1, D12S380E, D12S381E, and D12S382E). Based on STS content and
      fluorescence in situ hybridization experiments, two stable, nonchimeric YAC
      clones were found that span the mesothelioma breakpoint. A long-range restriction
      map of an 800-kb region was constructed and used to refine the mesothelioma
      breakpoint to a region of approximately 100 kb, flanked by the potassium channel
      genes KCNA1 and KCNA5. The latter was confirmed by direct visual hybridization
      (DIRVISH) experiments, using cosmids isolated for markers flanking the breakpoint
      as probes.

PMID- 7587393
TI  - Mapping segmental imbalances using comparative genomic hybridization and
      eigenanalysis.
AB  - We have tested a new approach to comparative genomic hybridization (CGH) analysis
      using digital ratio images and eigenanalysis, which allows the recognition of
      consistent patterns along the chromosomes and discards random (background noise)
      patterns. We have performed test experiments using genomic DNAs from a patient
      with a duplication, another with a deletion of a chromosome segment, and a
      prostate cancer biopsy. Image ratio analysis was performed, and ratio images of
      the relevant chromosome were subjected to eigenanalysis. The results showed a
      high-contrast enhancement of the regions corresponding to the unbalanced genomic
      segment, with clearly defined limits between normal and abnormal fluorescence
      ratios. The combination of digital ratio images and eigenanalysis allowed the
      precise mapping of unbalanced regions consistent with other methods of analysis.
      Because there is no limit to the number of chromosomes that can be analyzed at
      any one time, the method has the potential of increasing the sensitivity of CGH
      by reducing the noise component.

PMID- 7587394
TI  - Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell
      lines with a t(X;1)(p11.2;q21.2) and the first report of a female case.
AB  - A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors
      arising in males. In this study two cell lines derived from this tumor type have
      been used to indicate the breakpoint region on the X chromosome. Both cell lines
      have the translocation in addition to other rearrangements and one is derived
      from the first female case to be reported with the t(X;1)(p11.2;q21.2).
      Fluorescence in situ hybridization (FISH) has been used to position YACs
      belonging to contigs in the Xp11.2 region relative to the breakpoint. When
      considered together with detailed mapping information from the Xp11.2 region the
      position of the breakpoint in both cell lines was suggested as follows: Xpter-
      >Xp11.23-OATL1-GATA1-WAS-TFE3-SY P-t(X;1)-DXS255-CLCN5-DXS146-OATL2- Xp11.22-
      >Xcen. The breakpoint was determined to lie in an uncloned region between SYP and
      a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are
      contrary to the conclusion from previous FISH studies that the breakpoint was
      near the OATL2 locus, but are consistent with, and considerably refine, the
      position that had been established by molecular analysis.

PMID- 7587395
TI  - A new reciprocal translocation (7q+;15q-) in the domestic pig.
AB  - A reciprocal translocation was identified in a phenotypically normal Large White
      boar. Chromosome preparations from the carrier were studied by flow sorting,
      chromosome painting and G-banding. The flow karyotype displayed one additional
      clearly distinguishable peak, while in situ hybridization and G-banding showed
      two abnormal chromosomes involved in the translocation. All the results suggested
      that the translocation involved chromosomes 7 and 15 and the karyotype
      investigated was 38,XY,rcp(7;15)(q24;q12). The parents and three full sibs of the
      carrier had normal karyotypes. It would seem that the translocation had arisen de
      novo.

PMID- 7587396
TI  - Molecular analysis of a novel subtelomeric repeat with polymorphic chromosomal
      distribution.
AB  - DNA from a 50-kb yeast artificial chromosome (YAC) containing one human telomere
      was characterized. Cloned sequences from the centromeric end of this YAC
      (designated yRM2001) localized to several human chromosomes by somatic hybrid
      panel mapping. The telomeric end of the YAC contained both (TTAGGG)n sequences
      and the previously characterized TelBam3.4 subterminal repeat element. A novel
      low-copy repeat element (designated HC1103) mapped 19 kb from the telomeric end
      of the YAC. This repeat was shown by fluorescence in situ hybridization to be
      present in several subtelomeric regions (3q, 12p, 15q, 19p, and 20p) and at an
      interstitial site (2q13-->q14) in all individuals studied, but to be
      polymorphically distributed at several other telomeres. The YAC vector-insert
      EcoRI cloning site was positioned 50 kb to 70 kb from chromosome termini in human
      genomic DNA using RecA-assisted restriction endonuclease (RARE) cleavage
      analysis. Our results suggest that the DNA segment cloned in yRM2001 contains a
      novel block of low-copy DNA consistently present at some human telomeres, but
      polymorphically distributed at others.

PMID- 7587399
TI  - Mapping of synapsin II (SYN2) genes to human chromosome 3p and mouse chromosome 6
      band F.
AB  - Synapsins are neuron-specific phosphoproteins of small synaptic vesicles encoded
      by two different genes. While the gene for synapsin I (SYN1) is on the X
      chromosome, we have now assigned the human and mouse synapsin II (SYN2) genes to
      autosomes. By using PCR primers derived from rat synapsin II cDNA sequences we
      were able to amplify homologous sequences of the 3'-untranslated regions and to
      localize the human SYN2 gene to 3p and the mouse Syn2 gene to mouse chromosome 6
      by single strand conformation analysis of PCR products from panels of somatic
      hybrid cell lines. The mouse gene was further mapped by FISH to chromosome 6 band
      F in a region of known conserved synteny with human 3p. Genotyping of a M.
      musculus x M. spretus backcross panel placed Syn2 close to a cluster of
      previously mapped loci on chromosome 6 in an interval between interleukin 5
      receptor alpha (Il5ra) and hematopoietic cell phosphatase 1C (Hcph). Both
      physical and genetic mapping data indicate that Syn2 is near two mutant loci
      defined by neuromuscular disorders, opisthotonus (opt) and deaf waddler (dfw).

PMID- 7587398
TI  - Assignment of the gene for human carbonic anhydrase VIII(CA8) to chromosome 8q11-
      >q12.
AB  - The human carbonic anhydrase (CA) VIII gene (CA8) has been mapped to chromosome 8
      at q11-->q12 by human-mouse hybrid mapping and by fluorescence in situ
      hybridization. The closely-linked human CA isozyme genes, CA1, CA2 and CA3, are
      also located on chromosome 8, but at q22, and therefore not closely linked to the
      CA8 locus.

PMID- 7587400
TI  - Glucose transporters and insulin receptors in skeletal muscle. Physiology and
      pathophysiology.

PMID- 7587397
TI  - Mapping of human inter-alpha-trypsin inhibitor family heavy chain-related protein
      gene (ITIHL1) to human chromosome 3p21-->p14.
AB  - Inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) is a
      novel glycoprotein isolated from human plasma. The cDNA encoding IHRP has
      recently been cloned from human liver cDNA libraries. We report the mapping of
      this gene (ITIHL1) by fluorescence in situ hybridization using a 2.5-kb cDNA
      fragment as a probe. ITIHL1 was localized to chromosome region 3p21-->p14 where
      the genes of heavy chain 1 and 3 of inter-alpha-trypsin inhibitor are located.
      This result, together with significant homology between the nucleotide sequences
      of ITIHL1 and the heavy chain genes, supports ITIHL1 as being a member of an
      evolutionary related gene family of ITI heavy chains. Northern blot analysis
      indicated that IHRP was predominantly synthesized in liver. From Southern blot
      analysis, it was tentatively concluded that ITIHL1 is a single copy gene.

PMID- 7587401
TI  - Induction of labor by PGE2 and other local methods. Physiology, methods and
      guidelines for patient selection.

PMID- 7587402
TI  - Clinical evaluation of voiding symptoms and uroflowmetry in elderly men. A
      prospective study.

PMID- 7587403
TI  - Thyrotropin releasing hormone. Occurrence and role outside the central nervous
      system.

PMID- 7587404
TI  - Nocturnal hypoglycaemia in patients with insulin-dependent diabetes mellitus.

PMID- 7587405
TI  - The epidemiology of fatal unintentional child injuries in Denmark.
AB  - The main object of this historical follow-up study in a dynamic population was to
      examine the extent of fatal unintentional child injuries in Denmark. Particular
      attention was paid to identifying risks and risk groups as targets for
      prophylactic measures. All 1,202 fatal injuries which occurred during 1976-85 and
      were reported to the police were included in the study. Death certificate
      information was supplemented by data from medical files, post-mortem medical
      examinations and police reports. The average mortality rate (MR) was 14.43 per
      100,000 person-years in the group of boys, and 8.21 per 100,000 person years
      among girls. The cumulative mortality proportion was 2.18 per thousand for boys
      and 1.25 per thousand for girls. The mortality for boys fell during the period,
      but remained constant for girls. In the last years of the study the mortality
      rate for both sexes approached the same level. Boys had an overall mortality rate
      twice that of girls (RR 1.75 (CI 1.56-1.97)). Mortality was highest in the first
      five years of children's lives, i.e. the period of motor development and
      increasing curiosity regarding their surroundings. An overmortality in the rural
      areas as compared with the urban areas was identified (RR 1.47 (CI 1.31-1.64)).
      One reason for this may be that children living in rural areas are exposed to
      greater risks in everyday life and that they must venture into the traffic for
      purposes of social contact. Traffic-related deaths comprised 58% of all
      unintentional injury deaths. In around 50% of all cases the cause of death was
      head injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587406
TI  - Outcome of treatment of chronic low back pain in inpatients. Effect of individual
      physiotherapy including intensive dynamic training in inpatients with chronic low
      back trouble, evaluated by means of low back pain rating scale.
AB  - The purpose of the present study is to evaluate the efficacy of the treatment
      regime for chronic low back pain patients of the impatient clinic of Ringe
      Rehabilitation Hospital, Denmark, by means of a modified version of Claus
      Manniche's Low Back Pain Rating Scale. Ninety-three patients were included, of
      whom 63 (67%) participated in the one year follow-up interview. RESULTS:
      improvements in subjective as well as objective measures when discharge scores
      are compared to admission scores. The one year follow-up scores are on the same
      level as the admission scores. More patients are at work, but still more patients
      receive pension for health reasons at the one year follow-up. CONCLUSION: The
      improvements achieved during admission do not last. We suggest that the patients
      should be more carefully selected for intensive treatment during admission, and
      that the treatment perhaps should continue beyond the inpatient period. Perhaps
      the regime should include psychological treatment and vocational rehabilitation,
      all to be offered at the same institution.

PMID- 7587407
TI  - Mycotoxins and interstitial lung disease.

PMID- 7587408
TI  - Gastroesophageal reflux disease and asthma. Reflux or reflex?

PMID- 7587410
TI  - When should inhaled corticosteroids be started for asthma?

PMID- 7587409
TI  - Gastroesophageal reflux-induced bronchial constriction.

PMID- 7587411
TI  - Image-guided drainage of complicated pleural effusions and adjunctive use of
      intrapleural urokinase. What would Hippocrates think?

PMID- 7587412
TI  - Testing the waters. Differentiating transudates from exudates.

PMID- 7587413
TI  - Clinical economics through the kaleidoscope.

PMID- 7587414
TI  - Interstitial pulmonary fibrosis and lung cancer.

PMID- 7587415
TI  - Was the Bishop right?

PMID- 7587416
TI  - Desquamative interstitial pneumonitis and diffuse alveolar damage in textile
      workers. Potential role of mycotoxins.
AB  - Five of 88 workers at a textile plant developed interstitial lung disease. Biopsy
      specimens from the three initial cases demonstrated desquamative interstitial
      pneumonitis and diffuse alveolar damage. Two of these patients developed
      hypoxemic respiratory failure despite high-dose corticosteroid therapy. A survey
      of the remaining textile workers (questionnaires, chest radiographs, and
      pulmonary function tests) revealed one new case. This patient, and one other with
      a compatible presentation, improved clinically upon leaving the workplace and did
      not require therapy. A comprehensive assessment of the work environment was
      performed in search of potentially toxic respirable agents. We propose that these
      cases represent desquamative interstitial pneumonitis-like reactions,
      occupationally related to aflatoxin inhalation.

PMID- 7587417
TI  - Diagnostic accuracy of transesophageal echocardiography for detecting patent
      ductus arteriosus in adolescents and adults.
AB  - To compare the accuracy of transesophageal echocardiography (TEE) with that of
      transthoracic echocardiography (TTE) in the detection of patent ductus arteriosus
      (PDA) in the adolescent and the adult, 40 patients with PDA and 50 patients with
      other congenital heart diseases were studied. All echocardiograms were recorded
      before cardiac catheterization and surgery. The echocardiographic diagnosis of
      PDA was made by direct visualization of a shunt flow in the duct. A mosaic flow
      in the pulmonary artery without direct visualization of the duct was considered
      possible but not definitely diagnostic of PDA. TEE showed greater sensitivity and
      negative predictive value than TTE (97% vs 42%, and 98% vs 68%, respectively; p <
      0.001) in confirming the diagnosis of PDA. The specificity and positive
      predictive value in establishing the diagnosis of PDA were the same for both
      techniques. In the subgroup of patients with Eisenmenger's syndrome, the
      sensitivity of TEE and TTE in confirming diagnosis of PDA was 100% and 12% (p <
      0.01), respectively. The sensitivity of monoplane and biplane TEE in the
      diagnosis of PDA was comparable (95% and 100%, respectively; p = NS). In
      conclusion, TEE was highly sensitive and specific in detecting PDA in adolescents
      and adults. It was also highly valuable for detecting the cause of pulmonary
      hypertension in patients with Eisenmenger's syndrome.

PMID- 7587418
TI  - Acute alterations of oxygen uptake and symptom-limited exercise time in patients
      with mitral stenosis after balloon valvuloplasty.
AB  - STUDY OBJECTIVES: To determine the acute influence of improvement in orifice area
      in mitral stenosis by percutaneous transluminal valvuloplasty (PTVP) on
      cardiopulmonary exercise capacity, treadmill walking time (TWT), oxygen uptake
      parameters at maximum exercise as well as at highest comparable workloads and
      parameters of breathing work were assessed pre- and post-PTVP. PATIENTS AND
      INTERVENTIONS: PTVP was carried out in 16 patients who had moderately severe
      mitral stenosis, bringing about an average increase in mitral valve orifice area
      from 1.0 +/- 0.1 cm2 to 2.2 +/- 0.5 cm2 (p < 0.0005). Based on standardized
      conditions, the patients (six in functional class A, five in class B, and five in
      class C according to Weber's classification) underwent symptom-limited treadmill
      cardiopulmonary exercise testing before as well as 2 days after PTVP. In
      addition, subgroup analysis (eight patients in sinus rhythm, eight patients in
      atrial fibrillation) was performed to determine a potential influence of the
      underlying cardiac rhythm on cardiopulmonary exercise parameters. To rule out a
      PTVP-independent training effect, a control group of ten patients with mitral
      stenosis underwent the same kind of cardiopulmonary exercise testing on 2
      consecutive days. MEASUREMENTS AND RESULTS: After-PTVP, TWT augmented by 19% (p <
      0.0005) in all patients. Maximum oxygen uptake in percent of predicted maximal
      values at peak exercise and at anaerobic threshold was enhanced by 10% (p <
      0.005). Ventilation at highest comparable workload was diminished by 10% (p <
      0.025), whereas oxygen uptake and oxygen pulse at highest comparable workload did
      not differ, reflecting both unaltered cardiac output at comparable workloads and
      a more economic ventilation, respectively. Furthermore, PTVP-mediated alterations
      of TWT, but not of oxygen uptake at peak exercise were more pronounced in
      patients in sinus rhythm than in those in atrial fibrillation, reflecting more
      effective economization of cardiac work and ventilation in the former subgroup.
      Except for a statistically significant increase of TWT of 5%, no clinically
      relevant differences between both exercise tests were found with respect to
      oxygen uptake in the control group. CONCLUSIONS: Impaired cardiopulmonary fitness
      in patients with moderately severe mitral stenosis is improved substantially by
      PTVP immediately after the intervention, mainly the result of acute reduction of
      pulmonary congestion and subsequent decrease in dead space to tidal volume ratio.
      Adherence to standardized conditions is considered crucial for comparability of
      cardiopulmonary data.

PMID- 7587419
TI  - The heart in sickle cell anemia. The Cooperative Study of Sickle Cell Disease
      (CSSCD).
AB  - The objective of this study was to obtain representative echocardiographic
      measurements of cardiac size and function in stable patients with sickle cell
      disease. This prospective, multicenter study utilized central reading of
      echocardiograms by an investigator blinded to other patient data. Stable
      outpatients from a balance of inner city and rural settings with SS phenotype and
      a broad age range were selected, because conflicting results from earlier studies
      were believed to be due to these patient selection criteria. Right and left
      ventricular dimensions and wall thickness, left atrial and aortic root
      dimensions, and systolic time intervals were measured. Body surface area indexed
      chamber dimensions and septal thickness were significantly increased from normal.
      Except for the right ventricle, chamber dimensions and wall thickness were
      inversely correlated with hemoglobin. The relationship between left ventricular
      dimension and hemoglobin was significantly dependent on age. Systolic time
      interval ratios were normal though left ventricular ejection time was prolonged.
      Shortening fraction was normal but velocity of circumferential fiber shortening
      was abnormally low. Stable patients with sickle cell disease have dilated
      chambers, septal hypertrophy, and normal contractility. Though left ventricular
      dilatation was inversely related to hemoglobin, age (duration of illness) was an
      important factor in that relationship. No specific cardiomyopathy was associated
      with sickle cell anemia.

PMID- 7587420
TI  - Gastroesophageal reflux-induced bronchoconstriction. Is microaspiration a factor?
AB  - STUDY OBJECTIVE: To evaluate the role of microaspiration in gastroesophageal
      reflux-induced bronchoconstriction. DESIGN: Prospective study blinded to the
      subject. SETTING: Outpatient laboratory of a 908-bed university hospital.
      PARTICIPANTS: Thirty nonsmoking adults divided into two groups: asthmatics with
      reflux (AR), 20; and subjects with gastroesophageal reflux (R), 10.
      INTERVENTIONS: Dual esophageal pH probe placed. Esophageal infusions of normal
      saline solution, 0.1N hydrochloric acid, then normal saline solution, each
      lasting 18 min, were followed by two 20-min recovery periods. Subjects remained
      in the supine position throughout. Spirometry and specific airway resistance
      (SRaw) performed at baseline, after each esophageal infusion and recovery period.
      Proximal esophageal acid exposure, a requirement for microaspiration, was
      assessed by the proximal esophageal pH probe. RESULTS: Peak expiratory flow rate
      (PEF) decreased with esophageal acid in the AR group and did not recover
      immediately despite esophageal acid clearance with a significant main effect of
      subject groups (p < 0.021) by repeated measures analysis of covariance. This
      decrease in PEF was not associated with the presence of proximal esophageal acid
      exposure (p = 0.618). Specific airway resistance increased in the AR group with
      esophageal acid and worsened despite acid clearance, especially during the second
      recovery phase, with a significant phase (p < 0.009) and group by treatment
      effect (p < 0.009). The presence of proximal esophageal acid exposure was not
      associated with this deterioration in SRaw (p = 1.0). CONCLUSIONS: Esophageal
      acid infusions given in the supine position caused a decrease in PEF and an
      increase in SRaw in the asthma with reflux group, which did not improve despite
      acid clearance. These responses were not dependent on proximal esophageal acid
      exposure. Also, SRaw continued to worsen during the recovery phase in the AR
      group, which may represent a delayed bronchoconstrictor effect. These data
      suggest that microaspiration does not play a significant role in esophageal acid
      induced bronchoconstriction.

PMID- 7587421
TI  - Effect of early vs late intervention with inhaled corticosteroids in asthma.
AB  - One hundred five consecutive patients with mild or moderate asthma not earlier
      treated with inhaled corticosteroids and with a need of an inhaled bronchodilator
      of three or more doses a week, and/or asthma symptoms during day or night, and/or
      peak expiratory flow (PEF) or FEV1 less than 75% of predicted normal values were
      given an inhaled corticosteroid for 2 years (budesonide delivered via an
      inspiratory flow-driven multidose dry powder inhaler [Turbuhaler]). According to
      duration of symptoms, they were divided into six groups; from a duration less
      than 6 months up to a duration more than 10 years. PEF and FEV1 were measured
      before and after treatment for 3 months, 1 year, and 2 years. In the groups of
      patients with a duration of symptoms less than 2 years, mean FEV1 and PEF were
      significantly higher at all time points as compared with the baseline and as
      compared with the groups of patients with a longer duration of asthma symptoms.
      The maximum effects were usually seen after 1 year's treatment with maintained
      control during the second year. A significant negative correlation was found
      between duration of symptoms and maximum increases in PEF (r = -0.34; p = 0.0006)
      and FEV1 (r = -0.32; p = 0.0012), a correlation remaining also after correcting
      for baseline airway function. No correlation was found between the age of the
      patients or earlier regular use of beta 2-agonists and improvements in airway
      function. The results give some evidence that early treatment of asthma with an
      inhaled steroid may prevent patients from developing chronic airway obstruction.
      They also support current asthma treatment guidelines advocating early
      introduction of inhaled anti-inflammatory drugs.

PMID- 7587422
TI  - Rapid onset of tolerance to the bronchoprotective effect of salmeterol.
AB  - INTRODUCTION: Twice-daily inhaled salmeterol for 4 weeks produces marked
      reduction in its acute bronchoprotective effect against methacholine. This
      investigation examined the onset of this effect over 5 days, and also assessed
      cross-tolerance with salbutamol. SUBJECTS AND METHODS: Ten asthmatic volunteers
      who were able to withhold beta 2-agonist therapy for 4 weeks before and during
      the study participated in a double-blind, crossover, placebo-controlled study
      with two random-order treatment periods: inhaled salmeterol, 50 micrograms twice
      a day for seven doses, and placebo in similar fashion. Methacholine inhalation
      tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose
      of the study inhaler 10 minutes after 200 micrograms of salbutamol. RESULTS:
      Baseline FEV1 value before doses 3, 5, and 7 of salmeterol (ie, 12 h after
      salmeterol) was significantly higher than all other (n = 7) values. Twenty-four
      hours after the last dose of salmeterol, the FEV1 was no different from that
      during the placebo period. The geometric mean methacholine concentration causing
      a 20% fall in FEV1 (PC20) after the first dose of salmeterol (6.1 mg/mL) was
      statistically similar to the value achieved 10 min after salbutamol after the
      placebo period (8.3 mg/mL), and these were significantly (analysis of variance, p
      < 0.00005) larger than the second, third, and fourth salmeterol days (3.4 mg/mL,
      2.6 mg/mL, 1.9 mg/mL, respectively). The methacholine PC20 10 min after
      salbutamol measured after the salmeterol period was significantly lower than
      after placebo (2.3 mg/mL vs 8.3 mg/mL; p < 0.001). CONCLUSIONS: Tolerance to the
      acute bronchoprotective effect of salmeterol was significant after the first two
      doses and progressively increased to the seventh dose. Tolerance to the acute
      bronchoprotective effect of salbutamol was significant after regular use of
      salmeterol for seven doses.

PMID- 7587424
TI  - Contribution of the respiratory muscles to the lactic acidosis of heavy exercise
      in COPD.
AB  - Patients with COPD usually are limited in their exercise tolerance by a limited
      ventilatory capacity. Lactic acidosis induced by exercise increases the stress on
      the ventilatory system due to CO2 generated by bicarbonate buffering and hydrogen
      ion stimulation. Patients with COPD are often observed to increase blood lactate
      levels at low levels of exercise. We wished to determine whether patients with
      COPD who experience lactic acidosis do so because of respiratory muscle
      production of lactate. Eight patients with moderate to severe COPD (FEV1 = 43.5
      +/- 11.6% predicted) and 5 healthy subjects performed 10 min of moderate constant
      work rate exercise either breathing spontaneously or volitionally increasing
      their ventilation for 5 min to approximate the peak minute ventilation seen
      during incremental exercise. During volitional increased ventilation, 3% CO2 was
      added to the inspirate to prevent alkalosis and hypocapnia. In neither the
      healthy subjects nor the COPD group was the end-exercise lactate level
      significantly higher during volitional ventilation increase than during
      spontaneous ventilation. Further, in the COPD patients, the blood lactate levels
      during volitional ventilation increase were much lower than during maximal
      exercise (averaging 2.4 vs 5.3 mmol/L) despite similar ventilation levels
      (averaging 50 and 53 L/min). We conclude that it is unlikely that the respiratory
      muscles have an important influence on the blood lactate level elevation seen
      during maximal exercise in COPD patients.

PMID- 7587423
TI  - Interpretation of eucapnic voluntary hyperventilation in the diagnosis of asthma.
AB  - Eucapnic voluntary hyperventilation (EVH) of dry gas is a physiologic
      bronchoprovocation challenge useful in the diagnosis of asthma. To determine the
      best parameter and threshold for diagnosis and the proper timing of postchallenge
      measurements, we reviewed 120 challenges, comparing the decrement from baseline
      in FVC, FEV1, mean forced expiratory flow during the middle half of the FVC
      (FEF25-75%), and peak expiratory flow rate (PEFR) each at 0, 5, 10, and 20 min
      postchallenge. After adjustment to a standard minute ventilation of 30 times the
      baseline FEV1 for 6 min, the mean response by 90 mild asthmatics differed from 30
      normal subjects in all four parameters (p < 0.0001). In asthmatics, maximum
      decline from baseline (mean +/- SEM) was as follows: FVC, 12.1 +/- 1.2%; FEV1,
      19.7 +/- 1.7%; FEF 25-75%, 33.5 +/- 2.5%; and PEFR, 29.0 +/- 1.9%. Normal
      subjects had a maximum fall as follows: FVC, 2.9 +/- 0.7%; FEV1, 3.8 +/- 0.7%;
      FEF25-75%, 11.8 +/- 2.0%; and PEFR, 11.5 +/- 1.0%. Based on comparison of
      receiver operator characteristic curves, FEV1 was more accurate than FEF25-75%
      and equivalent to FVC and PEFR. A threshold of 10% change or greater in FEV1 had
      a specificity of 90%, with a sensitivity of 63.3%. A threshold of 15% or greater
      had a specificity of 100%, with a sensitivity of 53.3%. The FEV1 fell by 10% or
      more in 55 of 90 asthmatics at 5 or 10 min after hyperventilation. Measurements
      at 0 or 20 min added two additional positive responses. We conclude that in the
      proper clinical setting, subjects whose FEV1 declines by 10% or more at 5 or 10
      min after EVH should be diagnosed as having asthma.

PMID- 7587426
TI  - Measurement of pleural fluid cholesterol and lactate dehydrogenase. A simple and
      accurate set of indicators for separating exudates from transudates.
AB  - OBJECTIVES: To evaluate the usefulness of diverse combinations of pleural
      cholesterol concentration, pleural or serum protein, and lactate dehydrogenase
      (LDH) levels for the differentiation of pleural exudates and transudates. DESIGN:
      Prospective laboratory study of pleural effusions. SETTING: Medical school
      hospital. PATIENTS: One hundred eighty consecutive internal medicine ward
      patients in whom the etiologic diagnosis of their pleural effusion was confirmed.
      MEASUREMENTS: Cholesterol concentration in pleural fluid and protein and LDH both
      in pleural fluid and blood serum. RESULTS: According to their etiology, 49
      (27.2%) of the effusions were transudates and 131 (72.7%) were exudates. Using a
      cutoff point of 45 mg for pleural cholesterol and values for protein and LDH of
      Light et al, the best diagnostic power corresponded to the combination of pleural
      cholesterol and LDH: cholesterol level over 45 mg/dL and/or LDH over 200 IU/L
      identified exudates with a sensitivity of 99% and a specificity of 98%. All the
      other combinations showed inferior values and the criteria of Light et al reached
      98 and 82%, respectively. CONCLUSIONS: The measurement of pleural cholesterol and
      LDH permits the separation of pleural exudates from transudates with an accuracy
      similar to the original report of Light et al, with the advantage of requiring
      only two laboratory determinations and no simultaneous blood sample.

PMID- 7587425
TI  - Treatment of complicated pleural fluid collections with image-guided drainage and
      intracavitary urokinase.
AB  - STUDY OBJECTIVE: We report the results of image-guided catheter drainage with
      adjunctive enzymatic pleural debridement in the treatment of empyemas and other
      complicated pleural fluid collections. DESIGN: Retrospective review. PATIENTS:
      One hundred eighteen patients with complicated pleural fluid collections were
      treated with image-guided drainage. There were 79 empyemas, 27 sterile loculated
      parapneumonic effusions, 10 sterile hemothoraces, and 2 sterile postoperative
      exudative effusions. Forty-one patients had failed prior large-bore thoracostomy
      drainage. The estimated age of the effusions at the time of image-guided drainage
      ranged from 1 to 175 days with a mean estimated age of 13 days. INTERVENTIONS:
      Patients were treated with image-guided placement of one or more 12F to 16F chest
      drains. Adjunctive urokinase instillation was used in 98 cases. Urokinase
      (100,000 to 250,000 U/mL) was instilled in 20 to 240-mL aliquots and reaspirated
      in 1 to 4 h. One to four instillations were performed per day until drainage was
      complete. MEASUREMENTS AND RESULTS: Drainage was successful in 111 cases (94%).
      Two patients died of sepsis with incomplete drainage. Five patients underwent
      decortication (three recovered and two died postoperatively). Fifty-three
      patients (45%) required placement of more than one drain. The mean duration of
      drainage was 6.3 days. Patients treated with pleurolysis required a mean of five
      instillations of urokinase. The mean total dose of urokinase used per case was
      466,000 U. There were no complications. CONCLUSION: Image-guided drainage with
      adjunctive pleural urokinase therapy is a safe and effective method of closed
      thoracostomy drainage of complicated pleural fluid collections and can obviate
      surgery in most cases.

PMID- 7587427
TI  - Cost-effectiveness of head CT in patients with lung cancer without clinical
      evidence of metastases.
AB  - OBJECTIVE: To estimate the cost-effectiveness of CT for detecting brain lesions
      in patients with lung cancer without clinical evidence of metastases. DESIGN:
      Decision analysis model comparing two different strategies for detecting brain
      metastases: brain CT routinely (CT-first) or brain CT only when patients develop
      neurologic signs and/or symptoms (CT-deferred). PATIENTS: Hypothetical cohort of
      patients with lung cancer with an unremarkable screening clinical evaluation for
      metastases. MEASUREMENTS: Net costs are calculated as the difference in costs
      between the two limbs of the decision tree. Net benefits are expressed as the
      difference in calculated years of life expectancy between the two strategies. Net
      costs are divided by net benefits, yielding the marginal cost per quality
      adjusted year of added life expectancy (C/QALY) for the CT-first strategy.
      RESULTS: In the baseline analysis, the C/QALY for the CT-first strategy is about
      $70,000. Improving the clinical evaluation as a screen for detecting brain
      metastases markedly increases the C/QALY. Increasing the cost of brain CT
      magnifies this effect. More effective treatment for asymptomatic brain metastases
      and better accuracy of CT for identifying resectable and unresectable brain
      metastases lower C/QALY. CONCLUSIONS: Although a threshold cost-effectiveness has
      not been defined for identifying "cost-effective" diagnostic procedures, the
      marginal C/QALY of the CT-first strategy is substantially higher than many
      accepted medical interventions. At current costs, the routine use of brain CT is
      not warranted in patients with lung cancer who have normal findings on a
      standardized clinical evaluation for metastases.

PMID- 7587428
TI  - Clinical characteristics of synchronous multiple lung cancer associated with
      idiopathic pulmonary fibrosis. A review of Japanese cases.
AB  - To define the clinical characteristics of multiple lung cancer (LC) associated
      with idiopathic pulmonary fibrosis (IPF), we reviewed 154 LC patients associated
      with IPF: 23 patients with synchronous multiple LC (IPF-multiple LC group) and
      131 with single LC (IPF-single LC group), and these were compared with 4,931
      patients with LC from 1975 to 1977 in Japan (whole LC group). In the IPF-single
      and IPF-multiple LC groups, most tumors were observed in male patients (91% and
      96%), smokers (94% and 100%), and in peripheral regions of the lung (91% and
      98%). The incidence of occurrence in the lower lobes, where a fibrotic shadow was
      prominent, was significantly higher in the IPF-LC groups (58% and 67%) than for
      the whole LC group (37%). The distribution of histologic types in the IPF-single
      LC group was similar to that of the whole LC group. However, the incidence of
      small cell carcinoma was significantly higher in the IPF-multiple LC group (33%)
      than for the IPF-single LC (14%) and whole LC (12%) groups. These results
      indicate that the features characteristic to synchronous multiple LC in patients
      with IPF are as follows: (1) male patients; (2) smokers; (3) small cell carcinoma
      histologic type; (4) lower lobes; and (5) peripheral type, all of which show a
      high rate of occurrence.

PMID- 7587429
TI  - The curative treatment by radiotherapy alone of stage I non-small cell carcinoma
      of the lung.
AB  - This review was initiated to assess the outcome of treatment with radical
      radiotherapy with curative intent for patients diagnosed as having stage I non
      small cell lung cancer. The study involved a retrospective review of 347 patients
      with T1 and T2N0M0 tumors treated at the Queensland Radium Institute during the
      period 1985 to 1992. The main reasons for not proceeding to surgery included poor
      performance status, old age, or refusal to submit to surgery. The median age for
      the group was 70 years, with the range being 34 to 90 years. Patients in this
      group were all treated by a standard technique involving external-beam
      radiotherapy to 50 Gy, minimum tumor dose, in 20 fractions over 4 weeks. The
      overall survival rate was 27% at 5 years with a median survival of 27.9 months.
      The 5-year recurrence-free survival was 23% with the median being 19.5 months.
      There was a strong correlation of survival to tumor size with 5-year survival
      rates being 32% and 21% for T1 and T2 tumors, respectively. Multivariate analysis
      found only T stage to be associated with overall survival (p < 0.01). In
      addition, the analysis showed that age younger than 70 years was a prognostic
      factor that approached statistical significance at the p < 0.05 level of
      significance. We conclude from this large series of patients with stage I non
      small cell lung cancer that radical radiotherapy with curative intent may be a
      viable alternative to surgery in those patients who either refuse surgery or are
      judged to be unfit for operation.

PMID- 7587430
TI  - Acute lung disease in the immunocompromised host. Diagnostic accuracy of the
      chest radiograph.
AB  - PURPOSE: To assess the diagnostic accuracy of the chest radiograph in the
      evaluation of acute pulmonary complications in immunocompromised patients.
      METHODS: The study included the chest radiographs in 149 consecutive acute
      pulmonary complications seen in immunocompromised patients in whom a definitive
      diagnosis was made. Twenty-four complications were in patients with AIDS and 125
      were in non-AIDS patients. The radiographs were separately reviewed in random
      order by two independent observers. The observers assessed pattern and
      distribution of radiographic findings and recorded their first-choice diagnosis.
      RESULTS: The most common complication in patients with AIDS was Pneumocystis
      carinii pneumonia (n = 21). In the non-AIDS patients, the most common
      complications included invasive aspergillosis (n = 25), drug reaction (n = 21),
      and Pneumocystis pneumonia (n = 20). A correct first-choice diagnosis was made in
      90% of patients with AIDS and 34% of non-AIDS patients. IN AIDS patients with
      Pneumocystis pneumonia, the correct first-choice diagnosis was made in 41 of 42
      (98%) readings by the two observers. In non-AIDS patients with invasive pulmonary
      aspergillosis, drug reaction, and Pneumocystis pneumonia, the correct first
      choice diagnosis was made in 38%, 26%, and 43% of readings, respectively.
      CONCLUSION: The chest radiograph is helpful in the differential diagnosis of
      acute lung disease in the immunocompromised host, particularly in patients with
      AIDS.

PMID- 7587431
TI  - C-reactive protein. A clinical marker in community-acquired pneumonia.
AB  - STUDY OBJECTIVE: To assess the range of plasma C-reactive protein (CRP) in
      patients presenting with community-acquired pneumonia and to compare the serial
      changes of this acute-phase protein with clinical outcome. DESIGN: Prospective
      hospital-based study, including separate retrospective case series. PATIENTS:
      Twenty-eight consecutive patients (mean age, 60 years) admitted to our hospital
      with community-acquired pneumonia were studied. Serial daily plasma samples were
      taken and assayed for CRP, tumor necrosis factor-alpha (TNF-alpha), and
      interleukin 6 (IL-6). Clinical parameters, laboratory data, and response to
      treatment were recorded. Four other patients considered to be antibiotic failures
      (three empyemas, one death) were studied separately. RESULTS: Two patients died.
      Of those who survived, mean (+/- SD) CRP values for days 1,2,3,4, and 5 were as
      follows: 136 +/- 43, 96 +/- 44, 53 +/- 36, 54 +/- 43, and 44 +/- 31 mg/L. CRP
      levels on day 1 in patients who had received antibiotics prior to hospital
      admission were significantly lower than those who had not, 107 +/- 42 and 152 +/-
      44 mg/L (p < 0.05). CRP levels did not correlate with other laboratory parameters
      or with recognized predictors of mortality. A CRP value that continued to rise
      despite antibiotic treatment was associated with infective complications or
      death. Only 52% of patients had detectable TNF-alpha and 24% detectable IL-6 at
      some point during their hospital stay. CONCLUSIONS: CRP is a sensitive marker of
      pneumonia. A persistently high or rising CRP level suggests antibiotic treatment
      failure or the development of an infective complication. These results suggest
      that CRP, rather than TNF-alpha or IL-6, may have a role as a clinical marker in
      pneumonia.

PMID- 7587432
TI  - The safety of air transportation of patients with advanced lung disease.
      Experience with 21 patients requiring lung transplantation or pulmonary
      thromboendarterectomy.
AB  - Air travel can cause severe respiratory decompensation in a patient with advanced
      lung disease due to high altitude hypoxemia. We report our experience in flying
      21 patients with advanced lung disease to a medical center remote from Israel for
      lung transplantation or pulmonary thromboendarterectomy (PTE). All patients had
      severe lung disease with marked hypoxemia (PaO2, 40 to 59) and 16 had significant
      pulmonary hypertension. Nine patients (with emphysema and pulmonary fibrosis)
      required single lung transplant, four (with cystic fibrosis and emphysema)
      required double-lung transplant, six (with primary or secondary pulmonary
      hypertension) required heart-lung transplant, and two (with major vessel
      pulmonary thrombosis) required PTE. All patients were flown by commercial
      aircraft to centers located 2,634 to 13,181 km away from Israel. Length of flight
      was between 4 and 21 h. Patients were given oxygen supplementation during the
      flight and were monitored by portable oximeters. All but three patients were
      hemodynamically stable and 19 of them were escorted by physicians. All but one
      hemodynamically unstable patient who died on board arrived safely at their
      destinations. We conclude that with careful preparation, sufficient oxygen
      supply, oximetric monitoring, and medical escort, almost any patient with severe
      lung disease can travel by air to any necessary destination.

PMID- 7587433
TI  - Effect of routine emergency department triage pulse oximetry screening on medical
      management.
AB  - PURPOSE: To determine the utility of routine triage pulse oximetry screening in
      emergency department (ED) patients. DESIGN: Prospective study using pulse
      oximetry to measure oxygen saturation of ED patients at triage. Saturation values
      were disclosed to physicians only after they completed medical evaluations and
      were ready to discharge or admit each patient. We measured changes in medical
      management initiated after disclosure of pulse oximetry values. SETTING AND
      PARTICIPANTS: The study included 14,059 consecutive patients presenting to triage
      at a university ED. MEASUREMENTS: Changes in select diagnostic tests: chest
      radiography, CBC count, spirometry, arterial blood gases, pulse oximetry, and
      ventilation-perfusion scans; treatments: antibiotics, beta-agonists, supplemental
      oxygen; and hospital admission and final diagnoses that occurred after disclosure
      of triage pulse oximetry values. RESULTS: Of 1,175 patients having triage pulse
      oximetry values less than 95%, physicians ordered repeat pulse oximetry on 159
      (13.5%), additional chest radiography on 5.4%, CBC count on 3.1%, arterial blood
      gases on 2.9%, spirometry on 0.9%, and ventilation-perfusion scans on 0.3%.
      Physicians ordered 178 new therapies on 134 patients (11.4%), including
      supplemental oxygen for 6.5%, antibiotics for 3.9%, and beta-agonists for 1.8%.
      Thirty-five patients (3.0%) initially scheduled for hospital discharge were
      subsequently admitted. Physicians changed or added diagnoses in 77 patients
      (6.6%). CONCLUSIONS: Providing physicians with routine triage pulse oximetry
      measurements resulted in significant changes in medical treatment of these
      patients.

PMID- 7587434
TI  - Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation
      over time predicts poor outcome.
AB  - BACKGROUND: Inflammatory cytokines (ICs) are important modulators of injury and
      repair. ICs have been found to be elevated in the BAL of patients with both early
      and late ARDS. We tested the hypothesis that recurrent injury to the
      alveolocapillary barrier and amplification of intra-alveolar fibroproliferation
      observed in nonresolving ARDS is related to a persistent inflammatory response.
      For this purpose, we obtained serial measurements of BAL IC and correlated these
      levels with lung injury score (LIS), BAL indexes of endothelial permeability
      (albumin, total protein [TP]), and outcome. METHODS: We prospectively studied 27
      consecutive patients with severe medical ARDS. Using enzyme-linked immunosorbent
      assay methods, levels of tumor necrosis factor-alpha (TNF-alpha) and interleukins
      (IL) 1 beta, 2, 4, 6, and 8 were measured at frequent intervals in both plasma
      and BAL. In 22 patients, bilateral BAL was obtained on day 1 of ARDS and at
      weekly intervals when possible. Right and left BALs were analyzed separately for
      IC levels, total cell count and differential, albumin, TP, and quantitative
      bacterial cultures. RESULTS: On day 1 of ARDS, the 10 nonsurvivors had
      significantly higher (p = 0.0002) BAL TNF-alpha, IL-1 beta, IL-6, and IL-8
      levels, which remained persistently elevated over time, indicating a continuous
      injury process. In contrast, the 12 survivors had a lesser elevation and a rapid
      reduction over time. Initial BAL IL-2 and IL-4 levels were significantly higher
      in patients with sepsis (p = 0.006); both increased over time in survivors and
      nonsurvivors. BAL levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 correlated with
      BAL albumin and TP concentrations but not with LIS or ratio of arterial oxygen
      tension to inspired oxygen concentration. BAL: plasma ratios were elevated for
      all measured cytokines, suggesting a pulmonary origin. On day 1 of ARDS,
      nonsurvivors had significantly higher (p = 0.04) BAL: plasma ratios for TNF
      alpha, IL-1 beta, IL-6, and IL-8. Over time, BAL:plasma ratios for TNF-alpha, IL
      1 beta and IL-6 remained elevated in nonsurvivors and decreased in survivors.
      CONCLUSIONS: Our findings indicate that an unfavorable outcome in ARDS is
      associated with an initial, exaggerated, pulmonary inflammatory response that
      persists unabated over time. Plasma IC levels parallel changes in BAL IC levels.
      The BAL:plasma ratio results suggest, but do not prove, a pulmonary origin for IC
      production. BAL TNF-alpha, IL-1 beta, and IL-8 levels correlated with BAL indices
      of endothelial permeability. In survivors, reduction in BAL IC levels over time
      was associated with a decline in BAL albumin and TP levels, suggesting effective
      repair of the endothelial surface. These findings support a causal relationship
      between degree and duration of lung inflammation and progression of
      fibroproliferation in ARDS.

PMID- 7587435
TI  - Plasma and BAL cytokine response to corticosteroid rescue treatment in late ARDS.
AB  - BACKGROUND: In late ARDS, a persistent and exaggerated inflammatory response
      causes recurrent injury to the alveolocapillary barrier and amplification of
      intra-alveolar fibroproliferation. When ARDS patients fail to improve,
      corticosteroid (CS) rescue treatment frequently leads to rapid improvements in
      lung function. We tested the hypothesis that response to CS treatment is related
      to suppressing the inflammatory response by comparing changes in lung function to
      inflammatory cytokine (IC) levels in the plasma and BAL. METHODS: Blood samples
      were obtained on days 1, 3, 5, and 7 of ARDS, and on days -5, -3, 0 (initiation
      of treatment), +3, +5, +7, +10, and +14 of CS treatment. Bilateral BAL was
      obtained on day 1 of ARDS, before administration of CS treatment, and at weekly
      intervals. We analyzed changes in IC levels during CS treatment in relation to
      improvements in lung injury score (LIS), indices of endothelial permeability, and
      final outcome. We also analyzed data to identify timing to a significant
      reduction in plasma IC levels and predictors of response. RESULTS: Nine patients
      entered the study. CS treatment was initiated 15 +/- 9 days into ARDS.
      Improvement in LIS (> 1-point reduction) was rapid (< 7 days) in five, delayed (<
      14 days) in two, and absent in two. Baseline plasma and BAL IC levels in study
      patients were similar to a previously reported comparison group of 12 ARDS
      nonsurvivors. No significant changes in plasma and BAL IC levels were observed
      before CS administration. Following initiation of CS treatment, significant
      reductions in plasma tumor necrosis factor-alpha and interleukin 6 (IL-6) levels
      were seen by day 7 in both rapid and delayed responders (p = 0.03). IL-1 beta was
      significantly reduced by day 5 (p = 0.04) in rapid responders and by day 10 (p =
      0.03) in delayed responders. In responders, improvement in LIS and BAL albumin
      paralleled reduction in plasma and BAL IC levels. At initiation of treatment,
      rapid responders had significantly lower tumor necrosis factor-alpha and IL-6
      levels. Nonresponders had a significantly higher plasma IL-6 level on days 1 to 3
      of ARDS (p = 0.004) and lower ratio of arteriolar oxygen tension to inspired
      oxygen concentration at initiation of treatment (p < 0.01). CONCLUSIONS: In
      patients with late ARDS and a low likelihood of survival, prolonged
      corticosteroid rescue treatment was associated with a reduction in plasma and BAL
      IC levels and parallel improvements in indices of endothelial permeability and
      LIS.

PMID- 7587436
TI  - Tracheal aspirates in long-term mechanically ventilated patients. A human model
      of gram-negative infection and airway inflammation.
AB  - It is well known that patients requiring long-term mechanical ventilation and
      tracheostomy have nearly universal airway colonization with Gram-negative
      organisms. However, useful parameters to objectively describe the airway
      inflammation associated with airway instrumentation and colonization have not
      been well define. In our respiratory care unit, patients who are medically stable
      except for ventilator dependence are readily available for longitudinal
      assessment of airway secretions and therefore provide a unique population for
      studying airway inflammation and infection. To quantitate production of
      respiratory secretions, we instituted a uniform protocol of suctioning over a 6-h
      period. Further, we devised a method of dilution and homogenization of tracheal
      aspirates that permits reproducible intrasample total cell counts (coefficient of
      variation, 4.6%). With these techniques, patients were then studied serially over
      a 4- to 7-week period. Total cell count, inflammatory cell differential, and two
      indices of airway inflammation, human neutrophil elastase (HLE) and soluble
      intercellular adhesion molecule-1 (sICAM-1) studied in the sol phase of
      secretions were monitored. The mean total cell count was 42.2 x 10(6) cells per
      gram of secretions when patients were clinically stable and not receiving
      antibiotics. The average differential was neutrophils 69.9%, macrophages 26.9%,
      and lymphocytes 2.8%. Mean active HLE was 35.6 micrograms/mL and mean sICAM-1 was
      83 ng/mL. Six patients during the period of observation received intravenous oral
      or aerosolized antibiotics for tracheobronchitis. A threefold drop in volume of
      secretions was measured (p < 0.018). The total cell count and percent neutrophils
      decreased from 76.4 x 10(6)/g of sputum to 54.9 x 10(6) and 72.2 to 54.9%,
      respectively. While these changes were not statistically significant, the
      absolute number of airway neutrophils over the 6 h decreased sevenfold (p <
      0.014). Similarly sICAM-1 burden (micrograms per 6-h period) also decreased
      significantly (p < 0.034). These patients provide a unique human model for future
      studies specifically designed to assess the effect of novel modalities of anti
      inflammatory and antimicrobial agents on respiratory secretions.

PMID- 7587437
TI  - Comparison of two predictive models for prognosis in critically ill patients in a
      Veteran's Affairs Medical Center coronary care unit.
AB  - STUDY OBJECTIVE: The acute physiologic and chronic health evaluation score has
      been developed to assess prognosis in critically ill patients. Knaus et al
      initially determined and validated diagnosis-specific coefficients for prediction
      of outcome in a group of multidisciplinary ICUs. Teskey et al found different
      coefficients for cardiac diagnoses in a retrospective analysis of coronary care
      unit (CCU) only patients. This study compares the actual mortality in a Veteran's
      Affairs Medical Center (VAMC) CCU with the mortality predicted by the two
      equations. DESIGN AND SETTING: Data were prospectively collected for patients
      admitted to the medical CCU at a university-affiliated, tertiary care VAMC.
      PATIENTS: Patients (n = 338) admitted to the CCU with the diagnoses of coronary
      artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF),
      arrhythmia (Arr), and other cardiac-related diagnoses. RESULTS: The entire CCU
      population showed no significant differences from either the predictions by Knaus
      et al and Teskey et al in 1991. However, when specific disease states were
      analyzed as a whole, significant differences from both prediction models for CAD
      and MI actual mortality were found. Teskey et al was a better predictor for the
      Arr and CHF population, while both were equally reliable for other. CONCLUSIONS:
      Either prediction model is reliable for a CCU population in general. However,
      diagnosis-specific coefficients of Teskey et al appear to correlate better with
      actual mortality for this VAMC. Significant outcome differences compared with
      those predicted may reflect the patient population specific to a VAMC.

PMID- 7587438
TI  - Breathing frequency and pattern are poor predictors of work of breathing in
      patients receiving pressure support ventilation.
AB  - OBJECTIVE: To evaluate the relationships between directly measured work of
      breathing (WOB) and variables of the breathing pattern commonly used at the
      bedside to infer WOB for intubated, spontaneously breathing patients treated with
      pressure support ventilation (PSV). DESIGN: In vivo measurements of the WOB were
      obtained on a consecutive series of adults. Breathing frequency (f), tidal volume
      (VT), the index of rapid, shallow breathing (f/V T), the duration of respiratory
      muscle contraction expressed as the ratio of inspiratory time over total
      respiratory cycle time (TI/TTOT), and a breathing pattern score (applied to
      approximately 50% of the patients) which ranks f, VT, sternocleidomastoid muscle
      activity, substernal retraction, and abdominal paradox on a scale were variables
      of the breathing pattern were also measured. The greater the breathing pattern
      score, the lower the WOB and vice versa. SETTING: Surgical ICUs in two university
      teaching hospitals. PATIENTS: Sixty-seven adults (42 men and 25 women, aged 20 to
      78 years) who had acute respiratory failure from various etiologies were studied.
      All patients were breathing spontaneously receiving continuous positive airway
      pressure and PSV. INTERVENTIONS: Intraesophageal pressure (indirect measurement
      of intrapleural pressure) was measured with an esophageal balloon integrated into
      a nasogastric tube. VT was obtained by positioning a flow sensor between the "Y"
      piece of breathing circuit and the endotracheal tube. Data from these
      measurements were directed to a bedside respiratory monitor (Bicore; Allied
      Healthcare Products; Riverside, Calif) that calculates WOB using the Campbell
      diagram. Patients received PSV at levels deemed reasonable to unload the
      respiratory muscles. All measurements were obtained after 15 to 20 min at each
      level of PSV, averaged over 1 min, and then variables of the breathing pattern
      were regressed with directly measured values for WOB. RESULTS: All breathing
      pattern variables poorly predicted WOB as evidenced by the low values for the
      coefficients of determination (r2). Breathing frequency correlated positively
      with WOB (r = 0.47, p < 0.001) and predicted or explained only 22% (r2 = .22) of
      the variance in WOB. VT correlated negatively and f/VT and TI/TTOT each
      correlated positively with WOB. However, these variables predicted only 20 to 27%
      of the variance in WOB. The breathing pattern score correlated negatively with
      WOB and predicted only 43% of the variance in WOB. A prediction model taking all
      variables into consideration using multiple regression analysis predicted only
      50% of the variance in WOB; thus, it too was a poor to moderate predictor of WOB.
      CONCLUSION: Our data reveal that WOB should be measured directly because
      variables of the breathing pattern commonly used at the bedside appear to be
      inaccurate and misleading inferences of the WOB. The clinical implication of
      these findings involves the traditional and empirical practice of titrating PSV
      based on the breathing pattern. We do not imply that the patient's breathing
      pattern should be ignored, nor undermine its importance, for it provides useful
      diagnostic information. It appears, however, that relying primarily on the
      breathing pattern alone does not provide enough information to accurately assess
      the respiratory muscle workload. Using the breathing pattern as the primary
      guideline for selecting a level of PSV may result in inappropriate respiratory
      muscle workloads. A more comprehensive strategy is to employ WOB measurements and
      the breathing pattern in a complementary manner when titrating PSV in critically
      ill patients.

PMID- 7587439
TI  - A bedside ultrasound sign ruling out pneumothorax in the critically ill. Lung
      sliding.
AB  - STUDY OBJECTIVES: To describe and evaluate an ultrasound pattern useful in the
      diagnosis of pneumothorax. DESIGN: Ultrasound examination of "lung sliding," a
      respiratory movement visible when investigating the chest wall. SETTING: The
      medical ICU of a university-affiliated hospital. PATIENTS: The study group
      included 43 proved pneumothoraces, either by chest radiograph (n = 40) or by CT
      (n = 3). The control group included 68 hemithoraces in which the absence of
      pneumothorax was proved by CT. INTERVENTION: Analysis of anterior chest wall in
      supine patients. MEASUREMENTS AND RESULTS: Feasibility was 98.1%. Disappearance
      of "lung sliding" was observed in 100% of 41 analyzable cases of pneumothorax vs
      8.8% of the hemithorax without pneumothorax (6 of 68). In this series,
      sensitivity was 95.3%, specificity 91.1%, and negative predictive value 100% (p <
      0.001). CONCLUSIONS: Ultrasound was a sensitive test for detection of
      pneumothorax, although false-positive cases were noted. The principal value of
      this test was that it could immediately exclude anterior pneumothorax.

PMID- 7587440
TI  - Pulmonary artery rupture associated with the Swan-Ganz catheter.
AB  - OBJECTIVES: This study was designed to determine the incidence rate, define risk
      factors, and suggest proper management protocols for pulmonary artery (PA)
      rupture associated with Swan-Ganz catheters. DESIGN: This is a retrospective
      chart-review study. SETTING: This study involved 32,442 inpatients requiring
      hemodynamic monitoring with Swan-Ganz catheters in the operating rooms and ICUs
      at a large, private teaching hospital over a 17-year period (1975 to 1991).
      RESULTS: Ten patients sustained PA rupture, yielding an observed rupture rate of
      0.031% of catheter insertions. All ten patients had hemoptysis and five (50%) had
      pulmonary hypertension. Two patients (20%) had undergone anticoagulation at the
      time of rupture. Four of the six surgical patients were still in surgery at the
      first sign of rupture. A thoracotomy was performed in five patients. We noted a
      trend toward survival with thoracotomy, but it was not statistically significant.
      The overall mortality rate was 70%. When data from our 10 patients were combined
      with 65 patients from the literature, we found that thoracotomy was essential for
      survival in patients with hemothorax. There were no survivors among seven
      patients with hemothorax simply observed, compared with eight (50%) survivors in
      16 patients undergoing thoracotomy (p = 0.026). Thirty-nine (75%) of 52 patients
      without hemothorax survived, whether or not a thoracotomy was performed.
      CONCLUSIONS: Our study suggested that the incidence of Swan-Ganz catheter
      associated PA rupture is 0.031% and that an urgent thoracotomy should be
      performed if hemothorax is present at any point.

PMID- 7587441
TI  - The regional effect of retrograde cardioplegia in areas of evolving ischemia.
AB  - Retrograde cardioplegia (RCP) is often used for myocardial protection during
      coronary bypass grafting, but the regional effect of RCP in areas of evolving
      ischemia is unknown. We examined the functional and metabolic indices of regional
      myocardial preservation following acute coronary occlusion with evolving ischemia
      in a canine model. Following the institution of 37 degrees C cardiopulmonary
      bypass in 14 dogs, the left anterior descending artery (LAD) was occluded for 15
      min. The hearts were then subjected to 90 min of cardioplegic arrest (12 degrees
      C, 15 mL/kg every 30 min). Seven had antegrade cardioplegia (ACP) alone, while
      seven had ACP until arrest, then RCP. No topical cooling was used. The LAD
      occlusion was released after the first bolus of cardioplegia. Regional
      temperature and pH were measured in the LAD and circumflex (nonischemic)
      distributions. After 90 min of ischemia and 30 min of reperfusion, all dogs were
      weaned from bypass. Postischemic function was determined globally by the return
      of developed pressure (%dP/dt) and regionally by ultrasonic wall crystals. End
      ischemic ATP preservation in the LAD distribution was assessed by HPLC (mm ATP/mg
      protein). Results show that regional functional and metabolic indices were better
      maintained with RCP in the ischemic LAD distribution. Although only moderate
      reduction of global function was seen with ACP, the severe reduction noted in LAD
      regional wall motion with ACP reflects poor regional protection that can be
      significantly improved in evolving ischemia with RCP.

PMID- 7587442
TI  - The effects of brain death on cardiopulmonary hemodynamics and pulmonary blood
      flow characteristics.
AB  - Deterioration of donor lung function contributes to the shortage of donor organs
      and early postoperative failure after transplantation. A decrease in donor
      pulmonary function is associated with opacification of lung fields on
      radiographs, rendering the lungs unsuitable for transplantation, which may be
      related to the effects of brain death (BD) on pulmonary hemodynamics. Twenty
      mongrel canines (25.5 +/- 0.7 kg) underwent 20 BD experiments using a previously
      validated BD organ donor model. An ultrasonic flowmeter was applied on the
      pulmonary artery and micromanometers were inserted into the right ventricle,
      pulmonary artery, and left atrium to measure, which allowed the hemodynamic
      assessment and impedance profile analysis of the pulmonary vasculature by Fourier
      transformation. Characteristic impedance (Zo) was compared with input resistance
      (RIN) and with calculated pulmonary vascular resistance (PVR), the conventional
      index. Right ventricular hydraulic power was analyzed and divided in its
      components oscillatory and steady power. The results are expressed as means and
      SEM (analysis of variance, paired two-tailed t tests). Cushing reflex,
      hemodynamic response, and diabetes insipidus were consistent findings following
      BD. PVR, Zo, and RIN decreased significantly (p < 0.05) from 367 +/- 40 dyne.s.cm
      5, 226 +/- 13 dyne.s.cm-5, and 771 +/- 52 dyne.s.cm-5 to 261 +/- 25 dyne.s.cm-5,
      159 +/- 10 dyne.s.cm-5, and 651 +/- 69 dyne.s.cm-5 6 h after BD. Pulmonary artery
      blood flow increased significantly from 1,499 +/- 107 mL/min to 2,064 +/- 209
      mL/min (p < 0.05) after BD. Hydraulic power increased from 69 +/- 6 mW to 104 +/-
      13 mW (p < 0.05) and the oscillatory power to steady power ratio of 33%/67%
      changed to 23%/77% following BD. Extravascular pulmonary water content increased
      significantly by 10% after BD. BD causes a significant change in pulmonary
      vascular hemodynamics. The decrease in impedance and right ventricular afterload
      may lead to significant pulmonary overflow injury and edema. The increase in
      steady power represents an important reserve of the right ventricle to sustain
      pulmonary blood flow following BD.

PMID- 7587443
TI  - Comparative vasoactive effects of amrinone on systemic and pulmonary arteries in
      rabbits.
AB  - Amrinone has been increasingly used in management of low cardiac output syndrome
      during anesthesia, particularly when associated with right heart failure and
      pulmonary hypertension. This in vitro study was performed to determine and
      compare the direct vasoactive effects of amrinone on isolated rabbit systemic and
      pulmonary arteries. Responses of aortic and pulmonary artery rings from New
      Zealand white rabbits were assessed in the presence and absence of intact
      endothelium and with or without precontraction by norepinephrine (NE, 3 x 10(
      6)M) or potassium chloride (KCl, 3 x 10(-2)M). Using a tissue bath preparation,
      cumulative concentration response curves of amrinone were obtained at different
      concentrations after a period of stabilization. Amrinone caused a dose-related
      vasodilation of NE-precontracted aortic and pulmonary arteries. It elicited about
      65% and 90% relaxation, respectively, at a concentration of 300 mumol/L. Amrinone
      also induced a dose-related vasodilation of KCl-precontracted aortic and
      pulmonary arteries but to a lesser degree. All these effects were endothelium
      independent. By comparison, amrinone caused more relaxation in both NE- and KCl
      precontracted pulmonary artery than aortic rings. In conclusion, amrinone has
      significant endothelium-independent, direct vasodilatory effects on isolated
      rabbit systemic and pulmonary arteries, more pronounced in the latter,
      particularly NE-precontracted vessels. Amrinone may have some calcium channel
      blocking effect.

PMID- 7587445
TI  - Effect of pH and lidocaine on beta-adrenergic receptor binding. Interaction
      during resuscitation?
AB  - Epinephrine and other beta-adrenergic receptor (beta AR) agonists are often
      administered during cardiopulmonary resuscitation, a time when acid-base
      abnormalities and arrhythmias also commonly occur. We tested whether beta 2AR
      binding is influenced by pH or the antiarrhythmic drug lidocaine, and whether pH
      might influence the interaction of lidocaine with beta 2ARs. With institutional
      review board approval and informed consent, 32 venous blood samples were obtained
      from volunteers. Lymphocytes (which bear beta 2ARs similar to those found in
      heart) were isolated by density gradient centrifugation. Specific binding of the
      beta AR ligand 3H-dihydroalprenolol (3H-DHA) was determined with lidocaine
      concentrations ranging from 10(-6) to 10(-2) mol/L (n = 18 experiments), and with
      and without lidocaine (n = 10 experiments), 100 mumol/L, and with and without
      QX314 (a permanently charged lidocaine derivative), 1 mmol/L (n = 4 experiments).
      Data are presented as percent of control-specific binding measured at a pH of
      7.4. Statistical analysis consisted of Spearman's rank-test. 3H-DHA-specific
      binding increased (p < .001) with pH. Thus, alkaline conditions favored binding
      of 3H-DHA to the receptor. Lidocaine inhibited 3H-DHA binding to beta 2ARs in a
      concentration-dependent manner. The concentration that inhibited specific binding
      of 3H-DHA by 50% was 3.1 x 10(-4) mol/L (95% confidence limits, 1.3 x 10(-4) to
      7.5 x 10(-4) mol/L). Lidocaine potency at inhibiting beta 2AR binding also
      increased with increasing pH; thus, there was limited benefit (in terms of
      increasing binding to beta 2ARs) to increasing pH when lidocaine was present.
      QX314, despite being present in a 10-fold greater concentration than lidocaine,
      had no effect on 3H-DHA binding at any tested pH. The affinity of beta 2 ARs for
      both 3H-DHA and lidocaine increased with pH. Thus, the response to beta 2AR
      agonists (when no lidocaine is present) might be expected to be greater with
      normal or alkalotic pH than under acidotic conditions, supporting the correction
      of metabolic acidosis to achieve optimal effects from beta 2AR agonists during
      resuscitation.

PMID- 7587444
TI  - The effect of norepinephrine and dobutamine on bladder epithelial oxygen tension.
AB  - STUDY OBJECTIVES: To assess the effects of two contrasting vasoactive agents
      (dobutamine [DOB] and norepinephrine [NE]) on (1) global and regional
      cardiorespiratory variables, (2) acid base status, and (3) bladder epithelial
      oxygen tension (BEOT), a putative marker of organ perfusion. DESIGN: Measurement
      of aortic blood flow (ABF) and renal blood flow (RBF), mean arterial blood
      pressure, arterial blood gases, and BEOT were made during infusion of placebo and
      varying doses of DOB and NE. SETTING: Medical school laboratory. SUBJECTS:
      Eighteen anesthetized, spontaneously breathing, male Sprague-Dawley rats divided
      into three groups. INTERVENTIONS: Two groups were allocated to receive escalating
      doses of DOB (to 40 micrograms/kg/min) or NE (to achieve a 50% change in any
      hemodynamic variable). The drug therapy was then discontinued for 15 min and
      restarted at the previous maximum dose. A third group received 0.9% saline
      solution at the same infusion rate (16 mL/kg/h). MEASUREMENTS AND RESULTS: There
      was a dose-related increase in mean blood pressure with NE and fall with DOB.
      Compared with control values, NE had no effect on ABF but decreased RBF
      significantly whereas DOB significantly increased ABF but had no effect on RBF.
      Base excess and BEOT decreased significantly and in parallel with both agents,
      more so with NE. CONCLUSIONS: Despite their different macrocirculatory effects,
      DOB and NE both produced a significant but reversible fall in BEOT and a
      metabolic acidosis. BEOT shows potential as a monitor of the effectiveness of
      organ perfusion.

PMID- 7587446
TI  - Respiratory diseases disproportionately affecting minorities. The NHLBI Working
      Group.

PMID- 7587447
TI  - Applications and limitations of polymerase chain reaction amplification.

PMID- 7587448
TI  - Terminal weaning.

PMID- 7587449
TI  - Rapid withdrawal of support.

PMID- 7587450
TI  - The role of thrombin and thrombin inhibitors in coronary angioplasty.

PMID- 7587451
TI  - Pulmonary melioidosis.
AB  - Melioidosis is the name given to all diseases caused by the bacterium Pseudomonas
      pseudomallei. Melioidosis is a tropical disease and prevails in parts of
      Southeast Asia, northern Australia, and Central and South America. However, in
      recent years, cases of melioidosis have been reported in the United States and
      other areas. The organism can infect any organ system, although the lung is the
      most common organ affected. Pulmonary melioidosis presents either as an acute
      fulminant pneumonia or as an indolent cavitary disease. In northeastern Thailand,
      the incidence of P pseudomallei infection is extremely high with significant
      mortality. One of the key problems with treating melioidosis is its recalcitrance
      to therapy and high relapse rate. In addition, this Gram-negative rod is
      resistant to aminoglycosides. In nonendemic regions, patients with melioidosis
      more typically present with reactivation disease occurring months to years after
      initial exposure to the organism. The pulmonary disease is mainly in the apices
      and resembles tuberculosis. With the increasing mobility of people throughout the
      world and the influx of immigrants from endemic to nonendemic areas, it is
      important that clinicians be aware of this disease. This article will review the
      epidemiology, clinical presentations, diagnosis, and treatment of pulmonary
      melioidosis.

PMID- 7587452
TI  - Neutrophilic respiratory tract inflammation and peripheral blood neutrophilia
      after grain sorghum dust extract challenge.
AB  - STUDY OBJECTIVE: To determine if inhalation of grain sorghum dust in the
      laboratory would cause neutrophilic upper and lower respiratory tract
      inflammation in human volunteers, as well as systemic signs of illness. DESIGN:
      Prospective. SETTING: University of Nebraska Medical Center. PARTICIPANTS: Thirty
      normal volunteers. INTERVENTIONS: Inhalation challenge with 20 mL of a nebulized
      solution of filter-sterilized grain sorghum dust extract (GSDE). One group
      received prednisone, 20 mg for 2 days, prior to the challenge. MEASUREMENTS AND
      RESULTS: Bronchoscopy with bronchoalveolar lavage (BAL) was performed 24 h after
      challenge, with samples collected as bronchial and alveolar fractions. Findings
      included visible signs of airways inflammation, quantified as the bronchitis
      index. The percentage of bronchial neutrophils was significantly increased in
      those challenged with GSDE vs the control solution, Hanks' balanced salt solution
      (40.3 +/- 4.5% vs 14.3 +/- 5.1%, p < or = .01). Similar findings were seen in the
      alveolar fraction. Pretreatment with corticosteroids did not prevent the rise in
      neutrophils recovered by BAL. Peripheral blood neutrophils were also increased in
      volunteers challenged with the grain dust extract. To explain the increase in
      peripheral blood neutrophil counts, the capacity of the peripheral blood
      neutrophils to migrate in chemotaxis experiments was examined. The results
      demonstrate an increase in peripheral blood neutrophils and an increase in
      chemotactic responsiveness. CONCLUSIONS: Inhalation challenge with a grain dust
      extract causes respiratory tract inflammation and a peripheral blood
      neutrophilia. One reason for this may be an increase in activated peripheral
      blood neutrophils.

PMID- 7587454
TI  - Video-assisted thoracoscopic thymectomy for myasthenia gravis.
AB  - Video-assisted thoracoscopic surgery (VATS) provides a new approach to
      thymectomy. From June 1993 to December 1994, we performed a total of eight
      thymectomies for myasthenia gravis (MG). There were four male and four female
      patients with ages ranging from 9 to 76 years. Three of the eight patients had
      associated thymoma. We believe that complete thymectomy was accomplished in all
      cases by examination of the thymic bed and resected specimen. There was no
      mortality or intraoperative complications. The median postoperative hospital stay
      was 5 days (range, 2 to 37 days). One patient required ventilatory support
      postoperatively. Clinical improvement was observed in all patients after a mean
      follow-up of 10 months (range, 2 to 21 months). Compared with a comparable
      historical group of patients with MG who underwent transsternal thymectomy, the
      VATS group was associated with significantly less analgesic requirement and
      shortened hospital stay. We conclude that VAT thymectomy is technically feasible
      and is associated with a favorable postoperative course compared with the
      transsternal approach. We believe that complete thymectomy can be achieved by
      this approach. Further investigation with long-term follow-up is needed to
      further clarify the role of VAT thymectomy in thoracic surgery.

PMID- 7587453
TI  - Effect of residential cardiac rehabilitation following bypass surgery.
      Observations in Switzerland.
AB  - BACKGROUND: Cardiac rehabilitation in central Europe traditionally involves
      isolating patients in a residential idyllic setting where exercise is performed
      frequently but in a relatively unstructured fashion. Few studies have been
      performed on the effects of these programs among patients who have undergone
      bypass surgery. Recent data suggest that postbypass patients may enter these
      programs too soon after surgery or that exercise is not structured enough to
      distinguish the benefits of rehabilitation from those experienced by a control
      group. METHODS: Forty-two male patients (mean age, 58 +/- 7 years) were divided
      into exercise and control groups approximately 1 month after undergoing bypass
      surgery. Exercise training consisted of 1 h of group walking twice daily, with
      the intensity stratified into four levels based on initial exercise capacity.
      Using a crossover design, patients in the exercise group participated in
      rehabilitation for 1 month, followed by 1 month of usual care, while control
      patients underwent the opposite sequence. At 1, 2, and 3 months, patients in both
      groups underwent pulmonary function testing and maximal ramp exercise testing
      using lactate and gas exchange analysis. RESULTS: A main effect for maximal
      oxygen uptake was observed; significant improvements within each group occurred
      across each testing period (range, 5 to 13%; p < 0.05). However, there was no
      significant interaction between groups. Mean lactate levels throughout exercise
      were reduced within both groups (p < 0.01). A reduction in oxygen uptake for test
      2 at the lactate threshold in the exercise group resulted in differences between
      groups in lactate, heart rate, and other gas exchange variables at this point.
      CONCLUSION: Similar changes occur in the functional status of postbypass surgery
      patients regardless of their participation in the short but concentrated programs
      common in central Europe. This suggests that a significant spontaneous effect of
      healing occurs in the recovery phase after surgery. These programs may have
      greater efficacy if they began later after surgery, lasted longer, or were more
      structured, and studies are needed to determine their effect on psychosocial
      factors and return to work.

PMID- 7587455
TI  - Unilateral hilar mass.

PMID- 7587457
TI  - A 32-year-old man with hematuria and acute respiratory failure.

PMID- 7587459
TI  - Emergent bullectomy in a patient with severe bullous emphysema receiving
      mechanical ventilatory assistance.
AB  - This case report concerns a 29-year-old man with severe bullous disease who was
      admitted to the hospital with pneumonia and respiratory failure requiring
      mechanical ventilation. The patient underwent emergency bullectomy and was
      subsequently successfully weaned from the ventilator. He continues to do well 38
      months after the surgery. This case demonstrates that bullectomy, even in a
      patient receiving mechanical ventilatory assistance, can be a lifesaving
      operation.

PMID- 7587460
TI  - Influenza A pneumonitis following treatment of acute cardiac allograft rejection
      with murine monoclonal anti-CD3 antibody (OKT3).
AB  - A 51-year-old man developed fever, cough, and dyspnea 5 days after completing
      murine monoclonal anti-CD3 antibody (OKT3) treatment for acute cardiac allograft
      rejection. Samples of BAL fluid grew influenza A virus. Progressive pulmonary
      infiltrates, respiratory compromise, and hypoxia developed, and the patient
      ultimately required 5 days of mechanical ventilation. Treatment with amantadine
      hydrochloride and ribavirin was prescribed, and the patient was discharged after
      19 days. Influenza A virus has not been an important pathogen in cardiac
      transplant recipients. However, this is the first reported case of influenza A
      pneumonitis complicating anti-T lymphocyte therapy for cardiac allograft
      rejection. In comparison with our patient, two previously reported cases of
      influenza A infection in cardiac transplant patients have been less severe. The
      virulence of our patient's, life-threatening infection appears to be secondary to
      impairment of T lymphocyte-mediated immunity by OKT3. The role of therapeutic and
      even prophylactic amantadine therapy in this clinical setting has yet to be
      determined.

PMID- 7587456
TI  - A posterior mediastinal mass diagnosed by echocardiogram.

PMID- 7587458
TI  - Recurrent asthma, sinusitis, and rash in a 63-year-old man.

PMID- 7587461
TI  - Myocardial stunning following respiratory arrest.
AB  - Myocardial stunning is defined as a prolonged myocardial dysfunction with gradual
      return of contractile activity after a brief episode of severe ischemia. Usually
      it is seen in patients with myocardial infarction following treatment with
      thrombolytic agents, in patients with angina, and in patients recovering from
      cardiopulmonary bypass surgery. We report an interesting case of myocardial
      stunning following respiratory arrest.

PMID- 7587464
TI  - Aggressive fibromatosis of the chest associated with a silicone breast implant.

PMID- 7587462
TI  - Biopsy evidence of atrial myocarditis in an athlete developing transient
      sinoatrial disease.
AB  - Atrial myocarditis causing transient sinoatrial disease (incessant atrial
      tachycardia alternating with sinoatrial pauses of up to 6 s in duration) in an
      athlete is reported. Diagnosis was undertaken by endomyocardial biopsy;
      biventricular and right atrial specimens were obtained. After a 6-month rest
      period, the atrial arrhythmias disappeared, and the athlete was able to resume
      his professional sporting activities.

PMID- 7587463
TI  - Necrosis of the bronchus. Role of radiation.
AB  - The effects of radiation on the lung parenchyma and pleura are well described in
      the literature. Necrosis of the larynx is a known complication of radiation
      therapy. Necrosis of a part of the tracheobronchial tree following radiation
      therapy for bronchogenic carcinoma is likely to occur; however, there is little
      mention in the English-language literature about such an effect. This report
      describes four cases with total necrosis of a specific bronchus following
      radiation therapy for squamous cell carcinoma of the lung. All patients received
      5,000 to 6,400 rad (50 to 64 Gy) of external-beam radiation. Two patients
      presented with massive hemoptysis and two with pneumonia. In all four cases, the
      patients were found to have, by bronchoscopy, necrosis of the bronchus with the
      involved lobe of the lung replaced by a large cavity lined by tumor tissue.
      Diagnosis was made 5 to 7 months after radiation therapy was completed. Three of
      the patients died of exsanguination within weeks following diagnosis of the
      complication. We suspect that such necrosis occurs as a consequence of radiation
      therapy in combination with infection in the set up of squamous cell carcinoma,
      and is a marker of poor prognosis.

PMID- 7587465
TI  - Right-to-left flow through a patent foramen ovale in acute right ventricular
      infarction. Two case reports and a proposal for management.
AB  - Right-to-left shunting through a foramen ovale complicating acute right
      ventricular infarction and resulting in severe arterial hypoxemia has been
      described eight times before. Treatment strategies have often aimed at reducing
      the shunt. Four patients died. Less attention has been paid to attempts at
      revascularization and, despite a high incidence of atrioventricular conduction
      disturbances, to temporary dual-chamber pacing. We describe herein two patients
      with postcardiac surgical right ventricular infarction complicated by severe
      right-to-left interatrial shunting. Treatment strategy was aimed at improving
      right ventricular function, and right-to-left shunting ceased. All efforts should
      be directed at treating right ventricular dysfunction, which is the cause of the
      clinical picture, and not at reducing the shunt, which is a secondary phenomenon.

PMID- 7587466
TI  - Diagnosing pulmonary embolism.

PMID- 7587467
TI  - Treatment strategies for diaphragmatic myoclonus.

PMID- 7587468
TI  - Sarcoidosis and malignancy.

PMID- 7587469
TI  - Does ICU care determine the outcome of caring for patients with pneumococcal
      bacteremia?

PMID- 7587470
TI  - Confession and some lessons. The PISA-PED study.

PMID- 7587471
TI  - Heliox therapy for acute vocal cord dysfunction.

PMID- 7587472
TI  - Stridor from edema of the arytenoids, epiglottis, and vocal cords after use of
      free-base cocaine.

PMID- 7587473
TI  - Other local effects of nasal-continuous positive airway pressure.

PMID- 7587474
TI  - Differential diagnosis of postpartum pulmonary edema.

PMID- 7587475
TI  - The reduced sensation of dyspnea during exercise by inhaled oxitropium bromide in
      severe COPD patients.

PMID- 7587476
TI  - Comorbid disorders in hospitalized bipolar adolescents compared with unipolar
      depressed adolescents.
AB  - This study examined comorbid psychiatric disorders in adolescents with bipolar
      disorder. Hospitalized bipolar adolescents (N = 10) were compared to hospitalized
      adolescents with unipolar depression (N = 33), and to adolescents with
      nonaffective psychiatric disorders (N = 11). Results showed conduct disorder,
      attention-deficit hyperactivity disorder, psychosis, and having any DSM-III-R
      psychoactive substance use disorder were all significantly more common in the
      bipolar group than the unipolar depressed group. Comorbid anxiety disorder was
      present in 40-45% of the subjects in the unipolar and bipolar groups, but in none
      of the control group subjects.

PMID- 7587477
TI  - Importance of communication training for psychiatric residents and mental health
      trainees.
AB  - Through the illustration of a clinical vignette and excerpts from interviews with
      trainees, this paper suggests that communication and communication disorders are
      essential issues in child psychiatry training. The vignette shows how
      communication issues pervade a multidisciplinary psychoeducational day treatment
      program. The importance of communication in the clinical experience and its
      impact on the professional preparation of psychiatry residents and mental health
      trainees are examined, and conclusions and recommendations for the goals of a
      training program in child psychiatry are presented which expand upon those
      findings.

PMID- 7587478
TI  - Differences between conduct disordered and normal control children in their
      tendencies to escalate or neutralize conflicts when interacting with normal
      peers.
AB  - The behavior of conduct disordered (CD) children was compared with normal control
      (NC) children in interaction with normal peers. Dyads consisting of a) a CD child
      and a normal peer and b) an NC child and the same normal peer as in a) were
      observed. CD boys were less able than NC boys to neutralize incipient conflicts.
      Hitherto most behavioral studies of CD boys have concentrated on their tendency
      to escalate conflicts but have paid very little attention to their difficulty in
      neutralizing conflicts.

PMID- 7587479
TI  - Assessment of sexual abuse and trauma: clinical measures.
AB  - Examined are several measures currently used in the assessment of child abuse,
      sexual abuse, and trauma. These measures include structured clinical interviews,
      self report measures, screening inventory, symptom checklist, and some measures
      that include decision making properties. Issues and implications for clinical
      practice are explored.

PMID- 7587480
TI  - Aversive exchanges with peers and adjustment during early adolescence: is
      disclosure helpful?
AB  - We examined the relationship between the frequency of four types of aversive
      exchanges with peers (teased, threatened, hit, excluded), disclosure, and
      psychological distress in a sample of 130 early adolescents (65 boys, 65 girls).
      Most (73%) reported at least one aversive exchange with a peer during the 3-month
      target period. Many reported that they did not talk to anyone about these
      exchanges. When disclosure occurred, other adolescents were more likely than
      adults to be chosen as confidants. More frequent aversive exchanges and non
      disclosure of these events were related to higher self-reported loneliness for
      boys and girls. A similar pattern was found for girls only using mothers' ratings
      of the adolescents' internalizing and externalizing symptoms.

PMID- 7587481
TI  - Suicide: a review of calls to an adolescent peer listening phone service.
AB  - Calls about suicide to a teen peer listening phone service over a period of 5 1/2
      years are described. The majority of those calling about suicide were females.
      The phone contacts were of longer duration and later in the evening than calls
      about other concerns. Those concerned with suicide also discussed other serious
      issues such as self-esteem, family problems, substance use, and abuse and were
      less likely to be calling "just to talk."

PMID- 7587485
TI  - Effects of TNF alone or in combination with chemotherapeutic agents on human
      ovarian cancers in vitro and in nude mice.
AB  - Using the tetrazolium (MTT) assay, we examined the cytotoxicities of recombinant
      human tumor necrosis factor (rhTNF) and five chemotherapeutic agents, namely CTX,
      5-FU, VCR, DDP and KSM, on human ovarian cancer cell lines OVCAR3 and CAOV3. The
      results showed that the cytotoxicities of rhTNF at concentrations of 50-50,000
      U/ml on OVCAR3 cell line and CAOV3 cell line exposed to rhTNF for 24 hours were
      from 14.2% +/- 6.8% to 67.2% +/- 3.0% and from 8.2% +/- 4.3% to 60.9% +/- 1.3%,
      respectively. The cytotoxicities of all five chemotherapeutic agents tested on
      the two cell lines were much lower than that of rhTNF. We also studied the
      combined antitumor potential of rhTNF with the five chemotherapeutic agents and
      the results showed that there were various degrees of synergism in cytotoxicities
      of rhTNF in combination with DDP or KSM on the two cell lines. Based on
      experiments in vitro, the in vivo antitumor activities of rhTNF, both alone and
      in combination with KSM, were examined in OVCAR3 cancer transplanted in nude
      mice. The results showed a considerable antitumor effect of rhTNF when it was
      used alone and a marked synergistic effect when it was used in combination with
      KSM on the xenograft tumors.

PMID- 7587483
TI  - Recent advances in the study of the pathogenesis of nasopharyngeal carcinoma
      (NPC).

PMID- 7587484
TI  - Recent advances in clinical research of hepatocellular carcinoma in China.

PMID- 7587482
TI  - Advancement of tuberculosis control and research in China.

PMID- 7587486
TI  - The relation of parathyroid function to pregnancy-induced hypertension.
AB  - Parathyrin (PTH) and calcitonin were measured with radioimmunoassay in 39 cases
      of pregnancy-induced hypertension (PIH) in late pregnancy, 76 cases in normal
      early pregnancy and 278 cases in late pregnancy without PIH. Markedly increased
      PTH was noted in the women in late pregnancy, indicating the state of secondary
      hyperparathyroidism. PTH values in the women in late pregnancy with PIH were
      higher than those in the normal early pregnancy group, but lower than those in
      the women in late pregnancy without PIH. The difference between PTH values in the
      PIH group and late pregnancy without PIH group was of statistical significance (P
      < 0.05), while no significant difference was seen between calcitonin values of
      the two groups (P > 0.05). The results suggest that the pathogenesis of PIH may
      be related to the function of parathyroid.

PMID- 7587487
TI  - Endoscopic polypectomy for pacemaker patients.
AB  - Endoscopic polypectomy using high frequency voltage is contraindicated in
      patients with cardiac pacemakers. Recently, highly advanced pacemakers have
      enabled us to perform endoscopic polypectomy on these patients by taking
      appropriate cautions. We successfully removed 10 colonic polyps and one gastric
      polyp in patients with pacemakers by endoscopic polypectomy. No complication and
      dysfunction of the pacemaker occurred before, during or after the polypectomy.

PMID- 7587488
TI  - Dorsal scapular nerve compression. Atypical thoracic outlet syndrome.
AB  - The dorsal scapular nerve and long thoracic nerve of 10 cadavers (20 sides) and
      36 patients with dorsal scapular nerve compression were studied anatomically. The
      origin of the dorsal scapular nerve of a section frequently shared a common trunk
      with the long thoracic nerve, and went through the scalenus medius
      anterointernally and posterolaterally with the presence of some tendinous
      tissues. Leaving the long thoracic nerve, it might give branches to the shoulder
      and the subaxillary region and finally have the branches join the long thoracic
      nerve again. The compression of the section near the origin caused discomfort and
      sourness of the neck, shoulder and back region. Clinically, the severance of the
      scalenus anterior and medius ameliorated or relieved the compression of the
      dorsal scapular nerve. Complete decompression required cutting of the scalenus
      medius and its tendinous tissue superficial to the dorsal scapular nerve. Among
      24 sides of 22 patients undergoing surgery, the symptoms of 20 sides of 19
      patients were completely or partially relieved.

PMID- 7587489
TI  - Changes of endothelin during cerebral vasospasm after experimental subarachnoid
      hemorrhage.
AB  - Laser-Doppler flowmetry was employed in the observation of regional cortical
      blood flow (rCBF) after experimental subarachnoid hemorrhage (SAH) in
      anesthetized rats and the contents of endothelin (ET) in the cerebral-spinal
      fluid (CSF), plasma, hypothalamus, cerebral cortex, cerebellum and medulla were
      simultaneously measured. There was a biphasic change of rCBF after SAH. The
      contents of ET in CSF, plasma and hypothalamus rose prominently in the early
      stage after SAH, and the ET-increase in CSF and hypothalamus was earlier than
      that in plasma. The changes of ET contents in CSF correlated well with that in
      hypothalamus. Our results suggest that ET probably is an early important factor
      which induces cerebral vasospasm (CVS) after SAH. The increase of ET in CSF,
      which may originate from the hypothalamus, might play a more important role in
      the development of CVS after SAH than that in plasma.

PMID- 7587490
TI  - Long-term results after meniscectomy in 60 patients.
AB  - The long-term results of total meniscectomy in 60 patients were reviewed. The
      patients were followed up to 10 to 33 years. 58.3% of the patients had excellent
      or good results. Statistical analysis showed that the late results were related
      to the time of follow-up and not associated with the duration of disease before
      operation. Radiological degeneration of the knee was seen in 35 patients (87.5%),
      whereas no relationship of the degeneration to the clinical results was found. It
      is indicated that the menisci are so important in biomechanics that total
      meniscectomy should be avoided as far as possible.

PMID- 7587493
TI  - An immunocytochemical study on relations between mast cell and peptidergic
      terminals in nasal mucosa of chronic rhinitis patients.
AB  - Mast cell-nerve relation is a new topic explored deeply in different organs, but
      little documentation could be found in the literature on the relation in human
      nasal mucosa. We carried out this study using immunocytochemistry and found that
      substance P (SP) terminals were present in human nasal mucosa from six cases of
      chronic rhinitis. SP terminals were often found to be adjacent to or have a
      direct contact with mast cells (MCs). Electron-microscopic studies revealed that
      MCs could contact nonmyelinated nerve terminals. These results have important
      implications in the understanding of the pathogenesis of neurogenic inflammation
      seen in nasal mucosa and will probably cast new insight into the future treatment
      of such disease.

PMID- 7587491
TI  - Experimental study of fat embolism syndrome.
AB  - To find the diagnostic methods for subclinical stage fat embolism syndrome (FES),
      we established an experimental animal model, using fat intravenous injection. The
      fat was obtained from the long bone marrow cavity of homologous dogs. Fourteen
      healthy mongrel dogs received 0.7 ml/kg fluid marrow fat injection and all of
      them developed FES within 48 hours. The blood samples collected from the
      pulmonary vessels by floating catheter and peripheral vein at different time
      intervals were subjected to blood gas analysis and were frozen sectioned rapidly.
      The sections were stained with oil red 'O'. Positive result was seen 2 hours
      after fat injection in both pulmonary and peripheral blood. Computer image
      analysis showed that the number and diameter of fat droplets in pulmonary
      vascular blood were obviously higher and larger than those in peripheral vein
      blood. These findings were correlated well with blood gas changes and clinical
      features. The demonstration of fat droplets from pulmonary or peripheral blood by
      oil red 'O' staining combined with blood gas changes (PaO2 < 7.99 kPa, P(A-a)O2 >
      6.09 kPa) may be rapid and specific for early diagnosis of FES. In the treatment
      of FES, dexamethason can stabilize the cellular membranes and inhibit the
      neutrophil response to fatty acid and the release of phospholipase A2,
      arachidonic acid and platelet aggregation.

PMID- 7587494
TI  - Detection of human papillomavirus types 16, 18 DNA related sequences in
      bronchogenic carcinoma by polymerase chain reaction.
AB  - In studying the relationship between human papillomavirus (HPV) and bronchogenic
      carcinoma, "high-risk" HPV 16, 18 DNA sequences were detected in samples from 50
      lung cancer patients, 18 patients with benign pulmonary diseases and 4 fetal lung
      tissues by polymerase chain reaction (PCR) and dot-blot hybridization with biotin
      labelled probes. The results showed that HPV 16, 18 DNA related sequences were
      found in 32% of lung cancer specimens, with 10 cases of HPV 16, 5 cases of HPV 18
      and 1 case of both types. 48.15% (13/27) of squamous cell carcinomas were shown
      to be positive for HPV 16, 18 DNA. In addition, two adenocarcinomas and one small
      cell carcinoma were positive for HPV 16 DNA. No specimens from benign diseases
      tissues and fetal lung tissues showed positive results. These results suggest
      that primary bronchogenic carcinoma is related to HPV infection.

PMID- 7587495
TI  - The first report of echinococcus multilocularis in domestic dogs in Zhang County
      of Gansu Province.
AB  - In Zhang County of Gansu Province, 13 human cases of alveolar hydatid disease
      were reported up to 1990. However, the causative organism has not yet been
      described in animal hosts. In July 1990, postmortem examinations were made on 59
      dogs (Canis familiaris) from the Caotan region of Zhang County. Of them, 6 were
      found to be infected with the adult worms of Echinococcus multilocularis. The
      morphological characteristics of the adult were compared in detail with those
      reported from different parts of China. Our adult specimens were closely
      resembling those of E. multilocularis reported from Ningxia. The role of domestic
      dogs in the epidemiology of alveolar echinococcosis in Zhang County was
      discussed.

PMID- 7587492
TI  - Excimer laser photorefractive keratectomy for myopia in China. A report of 750
      eyes with a 6-month follow-up.
AB  - A total of 750 six-month follow-up records of myopia treated with excimer laser
      photorefractive keratectomy (PRK) were analyzed. By 6 months, in group 1 (up to 
      6.00D, 587 eyes), uncorrected visual acuity was improved to 20/20 or better in
      86.7% of treated eyes and 95.4% fell into the range of refraction of +/- 1.00D.
      In group 2 (-6.25D to -11.00D, 163 eyes), 74.5% of treated eyes had uncorrected
      visual acuity of 20/20 or better and 89.4% of the eyes were within +/- 1.00D. The
      designed predictability of the two groups was the same (P > 0.1). The refractive
      stability from 3 to 6 months between the two groups was not statistically
      different, and no severe complications were observed in these two groups. The
      excimer laser PRK for correcting myopia up to -11.00D appears to be effective,
      predictable, stable and safe in this study. The ideal outcome may result from the
      precise ablation quality of excimer laser, its computerized surgical manipulation
      and an appropriate postoperative management including detection of refractive
      indices by corneal topography and modulation by steroid.

PMID- 7587498
TI  - A pedigree of Y-linked retinitis pigmentosa. Investigation report of a family.

PMID- 7587496
TI  - The electrophysiologic effects of endothelin. A patch clamp study in guinea pig
      ventricular myocytes.
AB  - To study the electrophysiologic effects of endothelin-1 (ET-1), we used patch
      clamp and glass microelectrode techniques to investigate the effects of ET-1 on
      cardiac L-Ica, Ik and Ik2 in guinea pig ventricular myocytes. The prolongation of
      APD50 was induced and EADs was triggered by 50 nM ET-1 perfusion. L-Ica and Ik
      were enhanced by various ET-1 concentration from 1 to 50 nM with dose-dependence.
      Their steady-state activations of L-Ica and Ik shifted left with ET-1
      concentration increments. ET-1 elicited a kind of GTP-dependent inward rectifier
      K+ current having a mean conductance of 82.36 +/- 1.27 pS. The open time and
      close time (both interburst intervals and burst durations) abbreviated with ET-1
      concentration increase. The results suggested that EADs -ET evoked was ascribed
      to the prolongation on the plateau level, which resulted from L-Ica enhancement.
      The ET- evoked inward rectifier K+ current should be further studied.

PMID- 7587500
TI  - [Prof. dr med. Victor Dega 1896-1995 memorial].

PMID- 7587497
TI  - Prognostic efficacy of troponin T measurement in angina pectoris.
AB  - This study was designed to evaluate the efficacy of the newly developed Troponin
      T (TNT) enzyme immunoassay for predicting the prognosis of patients with angina
      pectoris. TNT, creatine kinase (CK) and MB isoenzyme of creatine kinase (CK-MB)
      were monitored in 134 patients with angina pectoris. There was no abnormality
      with any of these tests in 40 patients with stable angina pectoris and 30
      patients with unstable angina pectoris of Class 1 and 2 according to Braunwald's
      criteria. None of them developed acute myocardial infarction or other cardiac
      events. Elevation of TNT concentration with normal level of CK and CK-MB was
      found in 34 of the 64 cases of unstable angina pectoris of Class 3. Among the 34
      patients, 11 had acute myocardial infarction within 10 days during
      hospitalization. In contrast, only one of the patients with unstable angina
      pectoris of Class 3 with normal value of TNT developed acute myocardial
      infarction. As the incidence of angina pectoris is quite high clinically but only
      a small number of patients developed myocardial infarction, it is necessary to
      have a new assay of high sensitivity and high negative predictive value. TNT
      determination could meet these requirements as it had high sensitivity (92%) and
      high negative predictive value (98%) for the prognosis of unstable angina
      pectoris. If there is no rise of circulating TNT level, a favorable outcome can
      be expected with a high degree of probability. Determination of serum TNT level
      would be adopted as a routine procedure for evaluating the prognosis of angina
      pectoris and it is superior to other enzyme tests such as CK and CK-MB.

PMID- 7587499
TI  - A report on 8 seronegative converted HIV/AIDS patients with traditional Chinese
      medicine.

PMID- 7587501
TI  - [Treatment outcome for forearm shaft fracture using AO plate stabilization].
AB  - Results of treatment for 104 forearm shaft fractures in 70 patients have been
      presented. In all cases included in this study an open reduction of the fracture
      was followed by AO plate stabilization. Functional and radiological assessment
      was carried out according to the criteria of Anderson et al. Excellent and good
      functional results were achieved in 48 cases, fair in 10 and poor in 12 cases.
      The ulna united in 75%, the radius in 78% (delayed union included). Cross- union
      occurred in three patients, one case of destabilization at fracture site was
      observed, no infection has been noted. AO plate osteosynthesis proved to be still
      valuable mode of treatment for forearm shaft fracture.

PMID- 7587502
TI  - [Fracture of the C2 dens with severe dislocation without neurological deficit].
AB  - A case of dens fracture with severe dislocation not accompanied by spinal cord
      injury is presented. Cranial traction has been employed, reduction followed.
      Orthopedic neck brace has been used for further four weeks. Bony union has been
      achieved.

PMID- 7587503
TI  - [Kyphoscoliosis: etiology, pathology, complications and treatment].
AB  - On the basis of the literature and authors' own experience etiology, natural
      history and neurological complications of kyphoscoliosis are presented.
      Diagnostics and spinal pathology depending on the type of kyphoscoliosis is
      discussed. Surgical methods of kyphoscoliosis treatment and their role in
      prevention of neurological complications are reviewed. Their historical evolution
      is shown. At present, if neurological complications exist, decompression of the
      spinal cord and stabilization of the spine is recommended.

PMID- 7587504
TI  - [Terminology of scoliosis].
AB  - The most important entries concerning scoliosis have been presented in an
      alphabetical order. Some definitions, better describing three-planar scoliosis
      deformity, suggested by Scoliosis Research Society have been included.

PMID- 7587507
TI  - [Modifications of certain morphologic parameters in radiology of the hip joint].
AB  - The modification of some angles and indices used in radiographic hip measurements
      have been presented. Idelberger and Frank angles, "hip value", roof-head index,
      decentration index were discussed. Advantages coming from the use of those
      modifications have been exposed.

PMID- 7587505
TI  - [Ultrasonographic evaluation of the hip using Harcke's method in newborns and
      infants].
AB  - Theoretical foundations, technique of examination classification and own results
      of hip assessment with Harcke method in 256 newborns and infants has been
      presented. Simplicity of interpreting of the sonographic images, multiplanal,
      dynamic hip evaluation and potential to conduct assessment also in abduction
      device is underlined. Position II and III according to Harcke proved to be most
      useful for dynamic evaluation of the hip. Ossification center was seen earliest
      in position I; position III provided most significant information about hip joint
      morphology.

PMID- 7587506
TI  - [Treatment for complications of hip septic arthritis in newborns].
AB  - A series of 68 patients aged 3 months to 18 years treated for the sequele of
      septic arthritis of the hip in neonatal period at the Orthopedic Department in
      Lodz between 1964 and 1993 is presented. Modes of treatment depending on the age
      at the presentation, localization of the septic process and the extent of damage
      to articular structures are discussed. The results are reported in 42 cases with
      mean follow-up of 4 years (range 2 to 8 years). According to Hunck classification
      there were 36 good and 6 poor results. Closed reduction of the pathological
      dislocation of the hip in infants older then 6 months is not likely to succeed.
      Surgical intervention has never aggravated septic process. Poor results should be
      mainly attributed to great defects within the femoral head and neck. All the
      patients should be followed-up periodically for timely correction of deformities
      resulting from growth disturbances that increase with age.

PMID- 7587508
TI  - [Effect of implantation errors on increased osteolysis in cemented hip
      arthroplasty].
AB  - A retrospective standardized review of 76 cases of cemented hip arthroplasty has
      been done to evaluate the influence of technical errors on survivorship of
      prosthesis. Increased bone loss around the prosthesis was correlated to improper
      geometry of artificial hip joint and deficiency of the cementing technique.

PMID- 7587509
TI  - [Treatment outcome of juvenile slipped capital femoral epiphysis with Imhauser
      osteotomy].
AB  - Results of Imhauser osteotomy for treatment of slipped capital femoral epiphysis
      grade II and III performed in 32 patients (33 hips) are presented. The average
      correction of the slip angle was 39.7 +/- 14.9 degrees. Excellent results were
      found in 16 hips (48.5%), good in 10 (30.3%), fair in 5 hips (15.1%) and poor
      results in 2 hips (6.1%). No head-neck fixation after osteotomy did not lead to
      further slippage and decreased the risk of other complications. In 6 hips (18.2%)
      chondrolysis occurred. In one case prolonged immobilization of the hip was to
      blame, perforation of the femoral head in another, no cause has been identified
      in remaining cases. Avascular necrosis of the head was not observed.

PMID- 7587510
TI  - [Medial patellar plica of the knee in MR examination and arthroscopy].
AB  - MRI method of assessment of medio-patellar plica of the knee is presented. The
      results have been verified arthroscopically. Twenty seven patients have underwent
      MRI of the knee, arthroscopy followed in 15 cases. MRI revealed the plica in 15
      patients, no plica was found in 5 cases and 3 examinations were not conclusive.
      Arthroscopy confirmed pathology in 9 cases; the plica was also found in one of
      "not conclusive" cases. MRI rendered 0.7 specificity, 0.9 sensitivity and
      positive prognostic value was 0.6. MRI proved to be highly sensitive but
      delivered no means to differentiate symptomatic and asymptomatic plicae.

PMID- 7587511
TI  - [Use of planned preoperative autotransfusion in orthopedic surgery and
      traumatology].
AB  - The method for collecting autologous blood from patients awaiting elective
      surgery within locomotor system is presented. It was introduced with the use of
      existing infrastructure with minimal costs. No post-transfusion complications
      were noted in 103 patients included in this study. The method described proved to
      be worthwhile and allowing for limiting the use of homologous blood.

PMID- 7587512
TI  - Congenital pseudarthrosis of the tibia in children.

PMID- 7587513
TI  - Biopsy.

PMID- 7587514
TI  - The use of ceramic in prosthetic hip surgery. The state of the art.
AB  - The authors review current knowledge regarding the use of ceramic materials in
      prosthetic hip surgery, both as constituents of prosthetic components, and as
      materials used to coat metallic surfaces. A review of the literature defines the
      advantages and disadvantages to using ceramic-polyethylene or ceramic-ceramic
      combinations, based on the possibility that alumina coating may favor localized
      bone demineralization, and on the first promising clinical results of the use of
      hydroxyapatite coating.

PMID- 7587515
TI  - Total hip arthroplasty in patients dialyzed or with renal transplants.
AB  - The authors present 15 cases of hyp arthroplasty implanted in patients affected
      with necrosis of the femoral head, which were undergoing periodic hemodialitic
      treatment, or with renal transplants. Ceramic-ceramic prostheses were prevalently
      used and only in 1 case was a metal-polyethylene prosthesis used. Because of
      precarious mineralization a cemented prosthesis was implanted in dialyzed
      patients; in renal transplants, instead, cemented or cementless prosthesis were
      used depending on the state of the bone. There was a high percentage of excellent
      results after 2-8 years (87%), and this confirms the validity of surgical
      indications for the use of arthroplasty in hips affected with epiphyseal necrosis
      in order to favor functional recovery: considering the young age od the patients,
      this helps them to go back to being a part of society, and to recover
      psychologically.

PMID- 7587518
TI  - Microscopic lumbar herniectomy: our experience.
AB  - Based on the criteria proposed by Andrews the authors evaluate the results
      obtained in the first 87 patients submitted to herniectomy with the help of a
      microscope to treat lumbar disc herniation. The patients were followed-up 1-3
      months after surgery, and long-term follow-up was also obtained, after a mean of
      29 months. Results were judged to be satisfactory in 92% of the cases (80
      patients) at the first follow-up, while they were satisfactory in 94% of the
      cases (82 patients) at successive follow-ups. There was recurrence of disc
      herniation after 2 weeks which was resolved by revision surgery using
      microsurgical technique. Complications included laceration of the dura. The
      method proposed which is particularly widespread in neurosurgery is not
      considered to be revolutionary, rather it is a refinement, aided by progress in
      image diagnostics, of traditional surgery, of which it maintains the basic
      principles. Thus, without losing reliability and effectiveness, and with maximum
      respect for anatomy, it allows for excellent postoperative management.

PMID- 7587517
TI  - Partial arthrodeses of the wrist.
AB  - The authors report 16 cases of partial arthrodeses of the wrist for the treatment
      of Kienboeck's disease, pseudarthrosis of the scaphoid, rotatory subluxation of
      the scaphoid, rheumatoid arthritis, etc. Based on the good results obtained
      (76.6%) the authors believe that partial arthrodeses constitute the type of
      treatment indicated for the treatment of pathologies that involve only some of
      the carpal bones, and they also emphasize that this type of surgery represents a
      valid alternative to total arthrodesis of the wrist.

PMID- 7587519
TI  - Death rate in patients submitted to the surgical treatment of fracture of the
      proximal femur.
AB  - The death rate 6 and 12 months after surgery in 389 patients who had been treated
      for fracture of the proximal femur between 1989 and 1993 (1st semester) was
      studied. All of the patients submitted to surgery were traced through the
      official records on the population of the City of Padova. The overall death rate
      after 6 months was 16%, that after 12 months 23%. The best survival rate was
      observed in patients who had been submitted to gamma nail arthroplasty (p <
      0.01).

PMID- 7587520
TI  - Resection of the vertebral arch in the treatment of neoplasms of the spine.
AB  - The authors describe the surgical technique of en bloc resection of
      musculoskeletal neoplasms that originate and invade the posterior arch of the
      thoracolumbar spine. Surgery is indicated for the treatment of aggressive benign
      tumors (Enneking stage 3) and malignant tumors. For surgical margins to be
      adequate, both pedicles must be free of the tumor.

PMID- 7587516
TI  - Osteointegration of 96 cementless hip prostheses with hydroxyapatite coating; 5
      years follow-up.
AB  - Since 1988 at total of 96 hip prostheses with hydroxyapatite coating (HA) for
      both the acetabular and the femoral components have been used. HA is considered
      to be a biocompatible material, with a considerable capacity for osteointegration
      with evident osteophilia. Close integration between this material and bone tissue
      is determined by the formation of chemical bonds, and this leads to the
      development of osteoid tissue and newly-formed bone trabeculae. Based on the
      radiographic evaluation criteria described by Engh in 1990 and with reference to
      the concepts of stability and fixation of the prosthesis to the bone, it was
      observed that radiographic signs of osteointegration are manifested as early as 1
      year after surgery, and, in particular, that the formation of bone bridges (spot
      welds) in the interface increases in time.

PMID- 7587521
TI  - A histomorphologic study of explants of massive allografts: preliminary results.
AB  - The authors report their experience in the histologic study of massive
      allografts, explanted as a result of oncological, mechanical or biological
      complications. The study was conducted according to the method of inclusion in
      methyl methacrylate that does not involve decalcification. A description is
      provided of all of the phases of fusion between graft and host bone in the site
      of the osteotomies, as well as distribution of revascularization and
      rehabilitation of the graft, attachment of the soft tissues, and finally,
      modifications in the joint cartilage of the osteoarticular grafts. The allograft
      must be considered to be osteoconductive, and is only weakly osteoinductive.
      Incorporation of the graft is a slow and incomplete process that follows
      sequential phases. The Volkmann's canals in the osteotomies constitute the
      preferred paths for rehabilitation of the graft that is on the order of
      millimeters on the surface and centimeters in the site of the osteotomies. The
      greatest modifications have been observed in the joint cartilage. The
      cartilaginous cells appear to be vital only from a morphological point of view.

PMID- 7587529
TI  - [Spiritual ethical principles of surgical professional practice and imparting
      them to younger generations].

PMID- 7587530
TI  - [Economic recording of performance for managing documentation requirements].

PMID- 7587528
TI  - [Wolfgang Muller-Osten 85 years old].

PMID- 7587527
TI  - Quiz. Osteo-onychodysplasia (nail-patella syndrome).

PMID- 7587526
TI  - Voluntary hip dislocation in Down's syndrome: report of two cases.
AB  - Two cases of monolateral voluntary hip dislocation in Down's syndrome are
      reported. No surgical procedure was permitted by the family in either case, thus
      showing the natural evolution of the joint morphology. In the case observed a
      year after the onset of hip dislocation CT Scan already showed an initial
      smoothing of the posterior acetabular wall. In the other case, after a 9 year
      follow-up, the voluntary hip dislocation was followed by progressive subluxation
      and fixed dislocation at the end. This suggests that only early surgical
      treatment can prevent this outcome.

PMID- 7587524
TI  - The role of muscular co-contraction of the hip during movement.
AB  - The joint biomechanics of the hip was studied analyzing the kinematic, kinetic,
      electromyographic and in vivo pressure parameters during walking, going up
      stairs, and getting up from a chair. The most significant clinical and
      biomechanical data emerged when the temporal correlation between intra-articular
      pressure variations and electric activity of the bi-articular muscles was
      studied. The presence of co-contraction of the bi-articular muscles during the
      support and oscillation phases was evident. The maximum joint pressure values
      were measured while getting up from a chair when the hip was flexed more than 100
      degrees. The posterior region of the acetabulum was that most submitted to
      loading. This data is useful in gaining an understanding of joint physiology, in
      correctly setting up physio-kinesitherapeutic protocols, and in setting up pre
      clinical prosthetic mechanical tests.

PMID- 7587525
TI  - Relationship between osteoarthrosis and osteoporosis. An experimental and
      clinical study.
AB  - The authors conducted two studies to demonstrate the presence of a relationship
      between osteoporosis and arthrosis: the first study was experimental involving
      thirty femoral heads removed during hip arthroplasty, and the second was a
      clinical study conducted on forty patients with coxarthrosis. The results
      obtained confirm how the presence of one of the two pathologies may prevent or
      delay occurrence of the other, and on this basis the authors review the
      literature. Finally, also taking into account the interpretations of other
      authors, possible hypotheses on the inverse relationship that links the two
      pathologies are proposed.

PMID- 7587522
TI  - Computerized morphometric analysis of the femoral diaphyseal canal.
AB  - The constant increase in the use of hip arthroplasty and the continuous search
      for the best possible adaptation of the implant to femoral anatomy have led to
      the development of methods of radiographic analysis that are increasingly precise
      and reliable. Among these the methods that include the use of traditional
      radiograms-despite their limits-deserve a place of importance. In fact, these
      methods offer the advantage of being easy to apply and of allowing for a
      comparison to be made with pre-existing files. Computer science is useful in this
      field, in particular, computerized analysis, both morphometric and statistical,
      of the data acquired by digitizer. The protocol of acquisition and analysis that
      we applied to x-rays in anteroposterior view allowed for an evaluation to be made
      of some of the morphologic parameters of 354 femurs (corresponding to 264
      patients), relating them with the pathologies that led to hip arthroplasty. The
      duration of a cementless hip prosthesis strongly depends on primary stability.
      For this reason, an ever-increasing number of studies tends to make a precise
      evaluation of the morphology of the joint, in order to obtain excellent contact
      between bone and prosthetic component. The methods used are essentially
      radiological, with the use of computerized tomography and stereophotogrammetry.
      Morphometric studies of the proximal femoral area have in particular considered
      the width of the medullary canal at various levels; the cervico-diaphyseal angle;
      the flare index of the femoral canal (relationship between the internal
      metadiaphyseal diameter and that of the isthmus) and the distance between the
      rotation center of the femoral head and the diaphyseal axis. The evident absence
      of proportion between femoral sizes and shape of the medullary canal has led to
      the search for parameters capable of describing in simple fashion the shape of
      the femoral diaphyseal canal. A good describer of femoral morphology is the flare
      index, that allows for classification of the various shapes of the diaphyseal
      canal in three families: "stove-pipe like", "normal", "champagne glass like". The
      distinction between these groups is not clear, as the passage from one shape to
      another is gradual. The idea of obtaining more knowledge on femoral morphology,
      also to the purpose of determining possible new criteria that may be of help in
      preoperative planning and in the choice of a model to be implanted, has suggested
      our study on modifications caused by some of the pathologies that most frequently
      lead to arthroplasty.

PMID- 7587531
TI  - [German Interdisciplinary Society of Intensive and Emergency Medicine: comments
      on the emergency service in Europe].

PMID- 7587523
TI  - An experimental model to measure the torque of pin insertion and extraction for
      external fixation.
AB  - An original system used to measure torque of pin insertion and extraction in
      external fixation is presented. The system is made up of an electronic
      dynamometric key and an analogic/digital switchboard that may be linked up to a
      personal computer. The in vitro results show the simplicity of use and the
      versatility of the system, that is capable of providing the surgeon with accurate
      indicative values as to the mechanical resistance of the bone-pin interface
      during implantation of any fixator.

PMID- 7587532
TI  - [Common recommendations of the German Interdisciplinary Society of Intensive and
      Emergency Medicine and representatives of the Federal Medical Office on quality
      management in emergency medicine].

PMID- 7587533
TI  - [Standards of quality medical performance in the tension field between
      rationalization and rationing. Report on the scientific symposium 17 and 18 March
      1995 in Mainz--presented by the Academy of Sciences and Literature, Mainz].

PMID- 7587534
TI  - [Hospital economics. Report of the 18 May 1995 meeting, conducted by Prof. A.
      Encke, Prof. E. Martin and Prof. P. C. Scriba].

PMID- 7587535
TI  - [Hygienic requirements in parenteral administration of drugs].

PMID- 7587537
TI  - [Risk factors for recurrence of Crohn disease after intestinal resection].
AB  - From 1965 to 1990, postoperative risk factors (age, sex, preoperative history of
      CD, initial location of CD, length of affected intestinum, extent of bowel
      resection) for recurrence of Crohn's Disease (CD) were retrospectively analysed
      from data of 172 patients (104 men, 68 women; age 14 to 65 yrs.) with primary
      bowel resection and compared with the international literature. The mean follow
      up interval was 10 (1-21) years. Additionally full thickness biopsies from
      resection margins of 66 consecutive ileocecal specimen (45 men, 21 women; age 21
      70 years) with ileitis were studied, histopathologically classified into 3 groups
      and correlated with the rate, manifestation and onset of early recurrence. The
      cumulative CD recurrence rate was 69% after 10 years and 86.4% after 15 years.
      There was no statistically significant correlation between recurrence rate and
      age, sex, initial location or extent of bowel resection, only an higher rate with
      an preoperative duration of CD longer than 5 years (p < 0.05). The histopathology
      of the ileocecal resection specimen showed no statistically significant
      differences of the recurrence rate within the 3 groups. Surgery cannot minimize
      the recurrence rate of CD after resection but do clearly improve the quality of
      life.

PMID- 7587540
TI  - [Electrocoagulation in patients with cardiac pacemakers: what should be
      considered?].
AB  - Since the early days of pacemaker development electromagnetic interference (EMI)
      has always been a major concern and challenge to engineers, producers and
      physicians. The latter has to be aware of adverse effects of certain electric
      medical devices used near or on a patient carrying a pacemaker. Although highly
      sophisticated circuits and filters inside modern pacemakers can reject most EMI,
      concerns still remain and normal pacemaker function can be affected. EMI can be
      triggered by a variety of medical devices such as electrocautery, magnetic
      resonance imaging, diathermy, cardioversion and defibrillation, therapeutic
      radiation and lithotripsy. This article addresses the possible effects of
      electrocautery and the precautions that should be taken in case such a device has
      to be used on a patient with a pacemaker.

PMID- 7587536
TI  - [Recurrent Crohn disease--definition and diagnosis].
AB  - Recurrence in Crohn's disease is a frequently encountered problem in the history
      of this chronic incurable disease. A number of studies have shown different
      recurrence and reoperation rates, which is partly due to different definitions
      and diagnostic strategies. 'Surgical relapse' as defined as reappearance of
      disease activity in operated patients, 'clinical relapse' after conservatively
      induced remission or 'endoscopical recurrence' with new pathological changes in
      the operated gut may be differentiated. The different definitions of recurrence
      are discussed and diagnostic procedures like endoscopical, laboratory or
      radiological methods are explained.

PMID- 7587539
TI  - [Surgical therapy of recurrent Crohn disease].
AB  - The surgical therapy of recurrent Crohn's disease requires due to a recurrence
      rate of 60% after 15 years special precautions. The major principle of therapy is
      a minimal resecting surgery. This concerns mainly strictures and stenosis.
      Strictures should be treated by stricturoplasty and stenosis by limited
      resection. Recurrent fistulas should be treated conservatively. Just in case of
      interenteric and enterocutaneous fistula with a concomitant short bowel syndrome,
      in blind ending fistulas with an abscess or in enterovesical fistulas we
      recommend immediate operation. The therapy of recurrent anorectal Crohn's disease
      underlies the same rules as the primary therapy. If necessary, proctectomy
      remains an important option. Also emergency surgery in recurrent Crohn's disease
      follows the same rules as in elective surgery.

PMID- 7587542
TI  - [Ultrastructural findings in pleural cysts in spontaneous pneumothorax].
AB  - Lung biopsies obtained by conventional thoracotomy from five patients (mean age
      33.6 years, range 21-45) following recurrence of spontaneous pneumothorax were
      studied by light, scanning, and transmission electron microscopy. The purpose of
      the study was to define abnormalities that predispose to air penetration through
      the intact wall of pleural blebs. Two types of blebs were identified either with
      a complete or with an incomplete layer of mesothelial cells. In those areas where
      the mesothelial cells were lacking, the walls only consisted of irregular,
      discontinuous collagen fibers. Increasing intraalveolar pressure may distort the
      net of collagen fibers and air penetration appears to be possible. The wall of
      pleural blebs is generally weakened by degenerative changes and may predispose to
      recurrence of pneumothorax. Therefore, wedge resection of the blebs including the
      underlying lung parenchyma is suggested for surgical therapy of pneumothorax.

PMID- 7587538
TI  - [Crohn disease: prevention and drug therapy].
AB  - In view of a high recurrence rate of Crohn's disease after surgical resection
      prophylaxis is desirable. The value of various medical therapies to maintain
      remission after surgery has thus far only partially been established in clinical
      trials. Therefore, no clear guidelines are presently available. In patients with
      complete resection and a low risk of recurrence prophylactic treatment seems not
      to be necessary. In patients with a high risk of recurrence prophylactic
      treatment is recommended. This recommendation is supported by some clinical
      trials, although major trials are still ongoing. 5-Aminosalicylic acid in a daily
      dose of ca. 2-3 g is the primary choice for prophylaxis of recurrence. It reduces
      the risk of recurrence presumably by about 50%. In patients with a complicated
      course of the disease who have undergone several previous resections
      immunosuppressive treatment with azathioprine (1-2 mg/kg body weight/day) is
      recommended to avoid further recurrences. Conventional corticosteroids are not
      effective for postoperative prophylaxis. Ongoing studies evaluate the non
      systemic steroid budesonide as prophylactic treatment. There is no specific
      nutritional therapy to prevent recurrences; however, patients are advised to
      avoid nutrients which they do not tolerate. When patients have a clinical relapse
      systemic or topical corticosteroids are the treatment of choice. In moderately
      active disease and in patients who refuse to take corticosteroids high dose 5
      aminosalicylic acid (at least 4 g/day) may be used alternatively. In patients
      with chronic complicated disease azathioprine is recommended.

PMID- 7587543
TI  - [Segmental bile duct bypass in obstruction of the liver hilus: only an
      alternative?].
AB  - Between 1987 and 1992 unilateral, segmental bilioenteric bypass-procedures (30
      round ligament approach procedures, 4 peripheral bypass-procedures to the segment
      III bile duct and 3 to the segment V bile duct) were carried out in 37 icteric
      patients (twenty cholangio-carcinomas, 8 gallbladder-carcinomas, 6 other
      malignomas, 3 benign strictures). Postoperative complications were seen in 17
      (46%) patients. The 30 day mortality rate was 3% (1/37). Relief of symptoms were
      achieved in 83% of patients. Objectively there was a significant postoperative
      reduction of serum bilirubin levels from mean 323 mumol/l to 109 mumol/(p <
      0.005) and of the alkaline phosphatase from 708 U/l to 336 U/l (p < 0.005)
      respectively. This was achieved irrespectively of whether the segmental bypass
      was draining a segment only or the whole liver. Unilateral segmental bilioenteric
      bypass-procedures achieve an effective palliation in the majority of patients.

PMID- 7587541
TI  - [The significance of regional lymphatic tumor cell dissemination in patients with
      resectable non-small cell bronchial carcinoma. Results of a prospective study].
AB  - Encountering the high incidence of tumor recurrences in patients with apparently
      resectable non-small cell lung cancer it has to be assumed that in many patients
      already at the time of surgery a tumor cell dissemination has occurred, which is
      underestimated by current staging procedures. We therefore conducted a
      prospective study to assess the frequency and prognostic significance of a nodal
      tumor cell dissemination by using an immunohistochemical assay. Disseminated
      epithelial cells were demonstrated in 35 (6.2%) out of 565 lymph nodes staged as
      tumor free by conventional histopathology and in 27 (21.6%) out of 125 patients,
      respectively. In pN0 patients disseminated tumor cells were detected in 11/70
      (15.7%) cases. In patients staged as pN1 and pN2 by conventional histopathology a
      tumor cell dissemination to additional lymph nodes was demonstrated by
      immunohistochemistry in 4/25 (16.0%) and in 12/30 (40.0%) patients, respectively
      (p = 0.019). Independent from tumor staging univariate survival analysis showed
      that the detection of a nodal tumor cell dissemination was associated with a
      reduced disease-free survival (p < 0.001). Multivariate analysis demonstrated
      that the detection of such cells is an independent prognostic parameter (p =
      0.005). In conclusion, the use of immunohistochemistry enables to identify many
      patients with a widespread regional tumor cell dissemination at the time of
      surgery. This finding could represent a new criterion for an adjuvant therapeutic
      regime.

PMID- 7587544
TI  - [Subjective assessment of quality of life, pain and surgical success after
      laparotomy for Crohn disease].
AB  - 239 patients following major surgery for Crohn's disease (mean 8 years after
      first operation) were interviewed by mailed questionnaire. Main target parameters
      included reduction of quality of life, intensity/frequency of abdominal pain, and
      grading of success of the most recent operation for Crohn's disease. These
      targets were correlated in univariate as well as multivariate statistics with 28
      different parameters of general medical history, surgical pretreatment, actual
      somatic and psychosocial findings. Reduction of quality of life correlated with
      stool frequency, employment status, rectal involvement, hematochezia, liquid
      stools, extraintestinal manifestations and time since first operation (all with p
      < 0.05 in multivariate analysis; listed in decreasing levels of significance).
      Abdominal pain at time of interview was significantly associated with actual
      intake of corticosteroids, stool frequency, employment status, extraintestinal
      manifestations, dietary restrictions, and number of previous operations (other
      than laparotomies). Regarding success of most recent laparotomy important
      parameters included stool frequency, intake of corticosteroids, number of
      previous laparotomies, hematochezia, and history of enterostomy. Overall,
      parameters of disease activity were found to be more important than
      characteristics of medical history or previous surgery. Despite marked symptoms
      in many cases 92% of the patients regarded the most recent laparotomy to be fully
      or partially successful. The results provide direct and indirect evidence that
      besides momentary disease activity the individual personality profile may be far
      more important than type and number of previous surgery in coping with this
      chronic disease.

PMID- 7587545
TI  - [Laparoscopic resections in Crohn disease].
AB  - 39 patients with Crohn's disease underwent laparoscopic bowel resections during
      January 1993 to May 1995 (16 female, 23 male, with an average age of 33 years).
      The duration of the disease ranged from one to 18 years. 21 of the 39 patients
      were under steroid therapy at the time of operation. Seven patients have had
      ileocaecal resection for Crohn's disease. The operative technique is
      laparoscopically assisted. We performed: small bowel resections (8), ileocaecal
      resections (16), hemicolectomies (11), subtotal colectomies (2), colectomies (2).
      Operative time ranged from 90 to 280 min for ileocaecal resections and from 330
      to 420 min for colectomies. Intraoperative complications were not encountered.
      Postoperatively one patient developed a subhepatic abscess which was drained
      under sonographic guidance on day 6. One patient was reoperated for a different
      disease on postoperative day 2. Two patients had fever till day 9 and 13 without
      clinical relevance. Two patients had delayed incision site healing. Postoperative
      clinical stay was 11 days. The main benefit for the patients was early
      mobilisation due to reduced pain. Patients experienced the small abdominal
      incision as a ray of hope in their chronic disease.

PMID- 7587546
TI  - [Permanent electrostimulation of sacral spinal nerves with an implantable
      neurostimulator in treatment of fecal incontinence].
AB  - Functional deficits of the striated muscular anal sphincter frequently result in
      faecal incontinence. The therapeutic options for patients without a defined
      muscular defect are limited. Our patient without defined lesion, but with a
      clinically relevant reduction of the voluntary force of the anal sphincter
      resulting in daily loss of stool, underwent an electrostimulation procedure of
      the sacral spinal nerves. The procedure was divided in three steps: acute
      percutaneous testing, temporary percutaneous nerve evaluation and permanent
      electrostimulation phase with an implantable neurostimulation device. In all
      three phases electrostimulation of the third sacral spinal nerve resulted in a
      positive clinical effect and an increase of the anal canal closure pressure. By
      application of permanent electrostimulation of the third sacral spinal nerve the
      patient became completely continent.

PMID- 7587547
TI  - [Thoracic actinomycosis].
AB  - Thoracic actinomycosis is a rare disease without characteristic clinical signs.
      Approximately 90% of patients suffering from thoracic actinomycosis have
      undergone diagnostic and therapeutic procedures based on a wrong diagnostic
      hypothesis (malignancies 35-44%, other pulmonary disorders 33-35%). The
      opportunities for a timely and adequate diagnosis by the use of clinical
      examination, laboratory studies, microbiology studies, radiologic imaging or
      invasive measures are limited. In 85%, thoracic actinomycosis has not been
      identified prior to thoracotomy, open biopsy and histological examination. Based
      on a wrong diagnostic hypothesis, resective thoracic surgery according to the
      principles of oncologic surgery can hardly be avoided. We report on a 43-year-old
      male suffering from actinomycosis of the left hemithorax. Clinical signs,
      differential diagnosis, treatment and clinical course are described. The role of
      surgery in the treatment protocol of thoracic actinomycosis is discussed. In
      pulmonary and pleural disorders of unknown origin, differential diagnosis should
      include thoracic actinomycosis as early as possible. Due to the considerably high
      mortality rate of untreated disease, the outcome of thoracic actinomycosis can
      only be improved by a timely and combined employment of surgical and antibiotic
      therapy.

PMID- 7587548
TI  - [Rare manifestation of actinomycosis as retroperitoneal space-occupying lesion].
AB  - Actinomycosis has to be included in the differential diagnosis of retroperitoneal
      masses especially when surrounding tissue is infiltrated. We present a 40 year
      old male patient with the rare manifestation of retroperitoneal actinomycosis.
      The definitive treatment consisted of surgical drainage and long-term penicillin
      therapy resulting in complete healing. Special features in clinical
      symptomatology and problems concerning diagnosis of actinomycosis are discussed.

PMID- 7587549
TI  - [Ergotamine-induced anorectal lesions].
AB  - During the past 10 years several reports on perianal ulcerations secondary to
      chronic use of ergotamine suppositories were published. The present case reports
      deal with 2 female patients who used ergotamine suppositories for treatment of
      sick head aches for several years. In both cases the suppositories were used
      chronically. The first patient, a 60 year old woman has been treated repeatedly
      because of recurrent perianal ulcerations. An infection and a carcinoma could be
      excluded. The diagnosis of ergotamine induced ulcerations could be suspected only
      after a detailed work up of the patients past medical history and interview of
      family members. The ulcerations healed within a few months after broad excision
      and withdrawal of the medication. The second patient, a 51 year old woman
      complained of severe obstipation which occurred within a few months. The
      investigations showed a circular stenosis in the lower third of the rectum. The
      patient was treated successfully by bougienage under general anaesthesia. These
      case reports demonstrate the difficulties in diagnosis such lesions and emphasize
      the importance of a close medical follow-up when ergotamine suppositories are
      used for treatment of migraine. Whenever possible, a continuous treatment should
      be avoided.

PMID- 7587550
TI  - [Hans Bernhard Sprung (1906-1963) in Dresden and his students].
AB  - H.B. Sprung was the first head of the surgical clinic of the Dresden Medical
      Academy (today's Medical Faculty of the Technical University). In the hard time
      after World War II he didn't only found a new surgical building, but he also
      established an efficient surgery including anaesthesiology, neurosurgery,
      thoracic surgery and traumatology. Sprung got well known beyond the Dresden
      boundaries at the bottom of his works about the surgery of vegetative nervous
      system and about the gastro-intestinal diagnostic. During sixteen years of his
      work he educated many surgeons, which later carried out responsible jobs.

PMID- 7587551
TI  - [Hereditary non-polyposis colorectal cancer (HNPCC)--a determination ofthe
      current status. Report on the 1st Symposium of the German HNPCC Study Group in
      Dusseldorf 9 December 1994 and the 1st Professional Group Meeting 31 March 1995.
      Initiating a concerted action in Germany].

PMID- 7587553
TI  - [The future of radiology. Specialized radiology versus complete radiology-
      position of the Specialized Radiology Study Group of combined professional
      societies].

PMID- 7587554
TI  - [Basic principles of medical confidentiality within the scope of traffic safety].

PMID- 7587552
TI  - [The new structure of surgery continuing education in Germany].

PMID- 7587555
TI  - [Mode of genetic inheritance of abdominal aortic aneurysm: still no clear
      answers].
AB  - Clear evidence has not yet come concerning the genetics of abdominal aortic
      aneurysms (AAA). There are circumstantial proof for a hereditary predisposition.
      In a retrospective study of sixty patients consecutively underwent a surgical
      repair for AAA, showed that one third of them knew a first-degree relative with
      the same disease. Environmental factors, such as smoking, ageing or hypertension,
      must be taken into account. A multifactorial mode of inheritance is under
      discussion due to both multiple genes with different expressivity and diverse
      environmental factors. Linkage-analysis or DNA sequencing of the different gene
      loci in population studies or sibbling-analysis are the tools in search for
      candidate genes for inheritance of AAA. Mutations in those genes encoding
      structural components of the aortic wall, such as collagen-type-III, fibrillin or
      elastin, are not taken to be the underligned genetic cause. Mutations in genes
      encoding enzymes for the turnover of the aortic wall components, such as alpha-1
      antitrypsin or matrix-metalloproteinase-2, may play an important role.

PMID- 7587557
TI  - [Surgical treatment of infrarenal abdominal aortic aneurysm].
AB  - Results of surgical treatment of infrarenal abdominal aortic aneurysms (AAA) have
      improved in recent years. Through worldwide experience associated risk factors
      could be determined and reduced significantly. Therapy of associated diseases and
      profound morphologic knowledge about AAA are the most important factors to
      influence survival after surgery. Nowadays average mortality after elective
      surgery is 5%, 5-year survival rate 70%. By recognition of asymptomatic AAA on
      time the rupture rate with a mortality of more then 50% must be reduced in the
      near future. The purpose of this article is to represent, beyond the standard
      surgical technique, the possibilities to prevent ischemic complications from the
      myocardium, kidneys, colon and gluteal region during abdominal aortic surgery.

PMID- 7587558
TI  - [Endovascular reconstruction of infrarenal abdominal aortic aneurysm].
AB  - Animal experiments in the 80's demonstrated the feasibility of the concept first
      inaugurated by Dotter in 1969 of the endovascular implantation of a stent-graft
      prosthesis for the treatment of abdominal aortic aneurysm. In September 1990
      Parodi was the first to treat a patient with an AAA using the implantation of a
      TPEG (transluminal placed endovascular stented graft). The rapid development of a
      variety of different devices can be observed since resulting in about 400 such
      prosthesis being implanted world wide for the treatment of AAA. The experience
      accumulated so far shows that severe complications can be avoided if morphology
      based criteria are considered for the various treatment options (AAA
      classification type I, type IIa-c, type III). Despite considerable lethal
      incidents, technical mishaps and severe complications to date, the potential of
      TPEG for a structured approach to the treatment of AAA has to be evaluated.
      Prerequisites are 1) a competent team based on a close mutual cooperation of
      vascular surgeons and interventional radiologists, 2) a careful selection of
      patients, 3) TPEG to be performed in especially equipped operation theatres
      permitting the immediate application of conventional surgery if necessary, and 4)
      the implantation to be performed as a clinical study with flawless documentation
      of the procedure and follow-up.

PMID- 7587556
TI  - [Surgical treatment of thoraco-abdominal aneurysm. Indications and results].
AB  - Aortic replacement for thoraco-abdominal aneurysms remains a major challenge in
      vascular surgery. Related symptoms, maximal diameter > 6 cm, progression,
      aneurysm sac containing none or excentric thrombi and uncontrollable hypertension
      are factors in favour of surgery, if the general condition of the patient allows
      the operation. Patients with aneurysms < 5 cm maximal diameter, tube-size
      aneurysms, heavy calcification of the aortic wall, concentric thrombi within the
      aneurysmal sac and significant cardiopulmonary risks should be treated
      conservatively. Patients in good general condition with aneurysms around 5 cm
      maximal diameter should be controlled by computed tomography in 6 to 12 months
      intervals and in the case of progression surgery can be recommended despite
      missing symptoms. Crawford developed the 'graft-inclusion-technique', which
      combines the 'ingraft'-technique with reattachment of renal, visceral and
      segmental arteries. The 'clamp and repair' principle is used in patients with
      sufficient cardiac function. Otherwise shunt or left sided heart bypass are used
      to reduce cardiac afterload. According to the literature local cooling (flush
      perfusion), cytoprotective drugs and numerous methods to maintain or ameliorate
      distal aortic perfusion during clamping ischemia have been used in patients
      successfully for prevention of ischemic spinal complications. In physiological
      settings these methods may prove valuable, but under pathophysiological
      conditions of TAAA-repair one must doubt the efficacy, because the individual
      risk is difficult to assess. In our hands flush perfusion and cooling of the
      kidneys proved to be helpful. In animal experiments we have shown prolongation of
      ischemia tolerance time using eicosanoides to protect the kidneys and the spinal
      cord. If shunt or left-sided heart bypass can protect the spinal cord during
      clamping, is unknown, because the risk of paraplegia in the individual patient
      can be known only, if the function of the spinal cord is monitored. We have
      developed a spinal neuromonitoring system and found, that only one third of all
      TAAA-patients is at high risk to develop paraplegia during aortic clamping. The
      surgeon is guided by continuous recording of spinal evoked somatosensory
      potentials and can adapt the operative technique by early reimplantation and
      eventually subsequent separate reimplantation of segmental arteries supplying
      blood to the spinal cord, in order to reduce spinal ischemia time. Our results in
      260 TAAA-patients are presented. In a high-risk population of patients with
      aneurysms type I-III (Crawford's classification) it was possible, to reduce the
      paraplegia rate from 7 to 3.5%, the risk of paraparesis from 15 to 6%, while the
      operative mortality was only reduced from 19 to 10%.

PMID- 7587559
TI  - [Surgery of thoracic and thoraco-abdominal aneurysms using deep hypothermia and
      cardiovascular arrest with continuous administration of blood cardioplegia].
AB  - Between January 1991 and February 1993, 14 patients (3 female, 11 male) aged
      between 21 and 79 years (mean 50 years) underwent reconstruction of the thoracic
      (n = 7) and thoracoabdominal aorta (n = 7). Four patients had previously
      undergone operation of the ascending aorta, in 3 patients coronary artery by pass
      grafting was performed before. All patients were operated using cardiopulmonary
      bypass with continuous blood cardioplegia, hypothermic circulatory arrest (11
      degrees C nasopharyngeal temperature, 0-EEG) and posterolateral exposure. All
      patent lower intercostal and lumbar arteries (Th3-L5) were reimplanted. The 30
      day mortality after repair of the thoracic aorta was 0, after replacement of the
      thoracoabdominal aorta 28.5% (n = 2). One patient died 70 days after replacement
      of the thoracic aorta as a consequence of a perioperative stroke. None of the
      surviving 11 patients developed a permanent neurologic deficit, renal or cardiac
      dysfunction. The average intensive care stay was 6 days for patients after
      replacement of the thoracic and 18 days for patients after replacement of the
      thoracoabdominal aorta. Our results indicate the method of elective hypothermia
      and circulatory arrest effective in spinal cord protection. The increase in the
      tolerable duration of spinal cord ischemia supports the reimplantation of all
      intercostal and lumbar vessels.

PMID- 7587560
TI  - [Vascular injuries in war].
AB  - OBJECTIVE: This paper reviews military vascular injuries in Southern Croatia.
      BACKGROUND: Report of surgical procedures in war-related arterial and venous
      injuries in association with soft tissue destruction and bone involvement, with
      its post-operative medical and physical therapy. For vascular surgeons cases are
      presented, which are seldomly seen in civilian circumstances. For this reason
      this paper is published. PATIENTS AND METHODS: A retrospective review was done
      for 189 wounded (13 females, 175 males) with vascular injuries in the time period
      from June 1991 through December 1993. Ninety-one (48.1%) of the patients
      sustained injuries due to explosive weapons (different types of mines, grenades
      and its fragments). Extensive soft-tissue and bone destruction was associated in
      55 (36.2%) wounded. The age ranged from 14 to 63 (mean 27.3) years. The operative
      techniques involved the debridement of devitalised and infected tissue,
      prophylactic fasciotomy, the reconstruction of major venous injuries, application
      of microsurgical techniques in selected cases and the extensive use of autogenous
      interposition grafts. The wounds were treated by secondary closure and routinely
      antibiotics were given. In selected cases an arteriography was performed
      preoperatively. Vascular injury with a prolonged time of ischemia were the most
      common indication for hyperbaric oxygenation (HBO). RESULTS: Six (3.2%) patients
      died from associated severe injuries. In sixteen (15.1%) cases a subsequent
      amputation had to be performed. CONCLUSIONS: The results of this study support
      the reconstruction of major vessel damage in order to save a limb. Careful and
      regular follow-up examinations also by other medical specialties proved to
      enhance a positive outcome for this severely injured patients. We also suggest
      the extensive use of HBO in war casualties.

PMID- 7587562
TI  - [Thoracoscopic operation of primary spontaneous pneumothorax].
AB  - Since May 1990 we have treated 35 patients with spontaneous pneumothorax and
      without underlying lung disease by thoracoscopic operation. All patients entered
      a prospective trial. There have been four recurrences during a minimum follow-up
      of 7 months (median 19 months). Two complete collapses had had only fibrin glue
      sealant without any resection of bullae. The others were partial relapses not
      requiring any treatment. There was a striking high incidence of pain complaints
      and sensory disturbances (13 out of 29) even months after pleurodesis by
      coagulation or pleurectomy. Reduced trauma and less postoperative restriction of
      pulmonary function together with low recurrence rates suggest a more liberal
      indication in patients with their first manifestation of the disease.
      Nevertheless indication and choice of pleurodesis should be restrictive and be
      studied further for its specific complications.

PMID- 7587561
TI  - [Bacterial infections of the abdominal aorta].
AB  - There is a high mortality of bacterial aortitis particularly as it is usually not
      recognized before the stage of rupture. Therefore the disease should early be
      considered in obscure febrile conditions. Problems of diagnosis and therapy are
      discussed on two own cases. A 63-year old man had a rupture of a small infrarenal
      aortic aneurysm in the course of salmonella sepsis, a 79-year old woman had a
      pyogenic osteomyelitis of a lumbar vertebra that spread to the aorta and caused
      its rupture. In both cases surgical treatment consisted of bleeding control
      followed by in-situ reconstruction.

PMID- 7587565
TI  - [Surgical therapy of soft tissue sarcoma. I. General principles and resections of
      the trunk].
AB  - Resection, preferably wide resection is the primary treatment modality for
      localized (primary or locally recurrent) soft tissue sarcomas. Sarcomas of the
      chest or abdominal wall usually do not present great difficulty in their
      resection. When a mesh is used in the abdominal wall care should be exercised
      that there will be no direct contact between bowel loops and the mesh by using
      tissue interposition since otherwise the rate of bowel fistulization due to
      erosion by the mesh is considerable. Although the average rate of resectability
      in published reports in the United States for retroperitoneal sarcomas is 53%,
      with the incisions and techniques described below this rate is 95%.

PMID- 7587563
TI  - [Standardized laparoscopic hernioplasty vs. Shouldice repair. Results of a
      randomized comparative study].
AB  - From 5/93 up to 12/93 a prospective randomized trial was performed. 102 patients
      with unilateral primary inguinal hernias were included. In 48 patients a
      Shouldice repair and in 54 patients a laparoscopic TAPP procedure was performed.
      The laparoscopic method is described. There were significantly less pain and
      quicker mobility in the laparoscopic group. In addition a shorter period of
      disability of work was seen (21 vs. 38 days) in the same group. The morbidity of
      the procedures was as low in the Shouldice as in the laparoscopic group. There
      was a regular control of all patients. The current follow-up period is 16 months
      (13-21) in median. In both groups there were no recurrences up to now. The
      efficiency of laparoscopic hernia repair is discussed.

PMID- 7587564
TI  - [Intraoperative radiotherapy within the treatment concept of retroperitoneal soft
      tissue sarcomas].
AB  - Sarcomas of the retroperitoneum are characterized by a high rate of local
      recurrence. External beam radiotherapy is known to improve local control after
      surgical therapy. To increase local dosage of radiotherapy without affection of
      sensitive structures we applied intraoperative radiotherapy (IORT) since 1991 in
      a dedicated operative unit. To compare morbidity and tumor control we used a
      partly historic control group of patients treated since 1988 for retroperitoneal
      soft tissue sarcoma. 25 patients with a mean age of 53 years were operated. Tumor
      histology was dominated by liposarcoma and leiomyosarcoma, UICC stage IIB (T2 G2
      N0 M0) was present in 45% of cases. Distant metastasis were diagnosed in 19% at
      therapeutic intervention. Tumor free margins were achieved in 55% while 29%
      showed microscopic and 16% macroscopic tumor residues after surgical
      intervention. 11 patients received IORT with a mean of 18 Gy, eight of those
      patients were treated additionally with a mean of 40,4 Gy externally. There were
      no differences in distribution of known risk factors for recurrence in the group
      of patients treated with or without IORT. The analysis showed no difference for
      perioperative morbidity. Tolerance for IORT and additional external beam
      radiotherapy was good. Local tumor control tended to be improved by IORT (p =
      0.082) while overall survival was not affected at a mean follow-up of 24 months.

PMID- 7587566
TI  - [Angioscopy as intraoperative outcome control after reconstructive surgery of the
      renal arteries: presentation of a new method].
AB  - Main reasons for obstruction of renal arteries are atherosclerosis and
      fibromuscular dysplasia. In our clinic transaortic renal endarterectomy and
      interposition of a vein segment are preferred for arterial reconstruction. The
      surveillance of the distal intimal ridge after blind transaortic endarterectomy
      is still an unsolved problem, and the distal anastomosis of a vein graft must be
      checked, as it is performed under difficult conditions, if the suture is done in
      situ. We introduce angioscopy as a means of intraoperative surveillance.

PMID- 7587568
TI  - [Perforation of the heart wall--a rare complication after thoracic drainage
      treatment].
AB  - Complications after chest-tube treatment are rare if the correct technique is
      used. We describe a case of an iatrogenic perforation of the heart after bringing
      in a chest tube to treat a ventral pneumothorax during the postoperative
      intensive care treatment.

PMID- 7587569
TI  - [Hamartoma of aberrant breast tissue in the inguinal region].
AB  - Ectopic mammary tissue reportedly has an incidence of 1 to 6%, and is usually
      found in the axilla. Neoplasias in ectopic breast tissue are rarely observed.
      This is the first report of an hamartoma of ectopic breast tissue in the inguinal
      region. A 50-year old woman presented with a large tumor in the groin. The
      unusual site and form of the tumour preoperatively suggested a chronic
      incarcerated hernia. When laparoscopy excluded a hernia, the tumour was resected
      in accordance with oncological criteria and the histopathological work up
      revealed the surprising findings. This case shows that ectopic mammary tissue, in
      particular when it is the site of a tumor, may be a rare differential diagnosis
      of an inguinal tumor.

PMID- 7587567
TI  - [Traumatic injury of the internal carotid artery in the extracranial segment.
      Description of a severe late complication].
AB  - Blunt traumatic injury to the extracranial internal carotid artery may lead to a
      dissection with resultant stenosis, occlusion, or a dissecting aneurysm. Delayed
      clinical presentation weeks, months, and even years after the injury is rare, but
      has important diagnostic, therapeutic and forensic implications. In the current
      era, where computed tomography is replacing angiography as the main diagnostic
      procedure, it is extremely important to keep this diagnosis in mind. We report
      the case of a 31-years-old male patient, who did well after a motorcycle accident
      with head and neck injury for six years. Since then he only showed left-side
      Horner's syndrome, which unfortunately was ignored. In 1993 the patient developed
      occlusion of central retinal artery, and after a therapy with streptokinase he
      presented with right-side palsy and complete aphasia. CT-scan revealed a large
      edematous infarction in the middle cerebral artery territory. Transfemoral
      digital subtraction angiography however demonstrated a dissecting aneurysm of the
      left extracranial internal carotid artery as the source of intracranial
      embolization. Severe sequelae of this kind can only be warded of by early
      diagnosis and proper surgical therapy of vascular injury. Therefore even minimal
      symptoms suggesting the possibility of a traumatic injury to the carotid artery
      are recommending timely angiographic investigation.

PMID- 7587570
TI  - [Burning endotracheal tube. A complication of tracheotomy using electrocautery].
AB  - The cuff of an endotracheal tube was ignited during a trachetomy using
      electrocautery. The etiology of this complication is discussed as well as the
      prophylaxis and therapeutic management.

PMID- 7587571
TI  - [Resistance index of anterior cerebral artery in the diagnosis of hypoxic
      ischemic encephalopathy in neonates].
AB  - OBJECTIVE: To study the relationship between the resistance index (RI) of the
      anterior cerebral artery and hypoxic ischemic encephapathy (HIE) in neonates for
      the purpose of finding out a method of diagnosing and predicting HIE and its
      prognosis. METHOD: The anterior cerebral artery blood flow velocity waveform
      (aCAFV) of neonates was recorded by a continuous Doppler technique and RI value
      was measured. 230 observations on 67 cases of high risk neonates and 534 on 182
      normal neonates were performed. The mean value of RI and its standard deviation
      in normal neonates chosen served as control. The relationship between the
      standardized incidence of abnormal RI of the anterior cerebral artery and HIE was
      studied in high risk neonates. RESULT: In normal neonates (control group), RI was
      0.62 +/- 0.09, and was in positive correlation (r = 0.72, P < 0.05) with the days
      after birth. The normal aCAFV was a regular waveform. In high risk neonates, the
      standardized incidence of abnormal RI in the neonates most likely to be attacked
      by HIE (A group) was significantly higher than that in control group (P < 0.001),
      but there was no significant difference between the other babies (B group) and
      control group (P > 0.05). However, the standardized incidence of abnormal RI in
      the A group was also significantly higher than that in the B group (P < 0.001).
      In the cases who were severely attacked by HIE, the standardized incidence of
      irregular waveform was the highest. Furthermore, when irregular aCAFV waveform
      appears, the incidence of pernicious complication of HIE and mortality of
      neonates were significantly increased in all cases. CONCLUSION: The abnormal RI
      value of anterior cerebral artery implies the existence of HIE in neonates. The
      prognosis is poor when irregular blood flow waveform appears.

PMID- 7587573
TI  - [Urinary proteins during pregnancy in women with and without pregnancy induced
      hypertension].
AB  - OBJECTIVE: To study the excretion of urinary proteins in women at different
      periods of pregnancy and women with pregnancy induced hypertension. METHODS:
      Urinary proteins (albumin, IgA, IgG, IgM) were measured at random with enzyme
      linked immunosorbent assay (ELISA) in 101 normal pregnant women, 25 women with
      pregnancy induced hypertension and 28 nonpregnant women. RESULTS: Urinary albumin
      and IgM levels in women of early pregnancy were significantly higher than those
      in nonpregnant women (P < 0.05-0.01). Urinary IgG level was also increased during
      pregnancy. Urinary excretion of albumin, IgA, and IgG, but not IgM excretion was
      significantly elevated in women with pregnancy induced hypertension compared to
      normal pregnant women at different gestational ages (P < 0.05-0.01). Urinary IgM
      level in postpartum period was significantly lower than that in late pregnancy (P
      < 0.05). Urinary protein excretion increased with gestational age during normal
      pregnancy, but the changes were not statistically significant. However, the
      protein excretion was associated with severity of the diseases. Urinary albumin
      and IgG excretions in hypertensive pregnant women were correlated positively with
      mean arterial blood pressure. CONCLUSIONS: The change in glomerular filtration in
      pregnant women with mild to moderate hypertension is reversible. It is important
      to control blood perssure to avoid impairment of kidney function in pregnancy
      induced hypertension.

PMID- 7587574
TI  - [Clinical application of luteinizing hormone releasing hormone agonist and its
      impact on bone metabolism].
AB  - OBJECTIVES: To evaluate the efficacy of luteinizing hormone releasing hormone
      agonist (LHRH-A) in the treatment of endometriosis (Em), uterine leiomyoma and
      adenomyosis, and its impact on bone metabolism. METHODS: Twenty patients, Em 13
      (stage II4, III7, IV2), leiomyoma 4 and adenomyosis 3, were selected to receive
      LHRH-A 200 micrograms intramuscular daily for 3 months. Clinical and ultrasound
      features serum follicle stimulating hormone (FSH), luteinizing hormone (LH),
      estradiol (E2), osteocalcin (BGP) concentrations were compared before and at the
      end of treatment. Furthermore, 24-hour urinary calcium (Ca), phosphate (P)
      excretions and bone mineral density (BMD) of radius and lumbar spine measured by
      single photon absorptiometry (SPA) and dual energy X-ray absorptiometry (DEXA)
      were also analysed before and at the end of treatment. Patients were followed-up
      3-19 months after discontinuation of the drug. RESULTS: At the end of treatment
      dysmenorrhea disappeared in all 15 cases. Pelvic tenderness and induration
      improved in 18, endometrioma shrinked in 13 cases. Mean uterine volume of 7
      patients with leiomyoma or adenomyosis was reduced by 35% from the basal volume.
      Serum LH, E2 levels were suppressed significantly (P < 0.05), mean E2
      concentration declined from 459.5 +/- 292.0 to 160.3 +/- 110.7 pmol/L (P <
      0.001). No significant change was found in serum BGP, urinary Ca, P, and BMD of
      radius and lumbar spine at the end of therapy, The only side effect was mild not
      flushes and sweating during treatment. After stopping the drug, 17 patients
      resumed menses within 2 months. Dysmenorrhea and pelvic mass recurred in 6 months
      with less severity. One became pregnant in 3 months. CONCLUSIONS: LHRH-A
      administration is effective in the treatment of Em, leiomyoma and adenomyosis. No
      significant adverse effect was shown on bone metabolism at the end of 3-month
      therapy.

PMID- 7587572
TI  - [Observations on serum and amniotic fluid hormone levels and ultrastructure of
      uterine myometrium before and during term labor].
AB  - OBJECTIVES: To evaluate the relationship between serum and amniotic fluid (AF)
      estradiol (E2), estriol (E3), progesterone (Po), cortisol (Co), human placental
      lactogen (hPL) concentrations and uterine contractions. To observe the
      ultrastructural changes of uterine myometrium before and during labor. METHODS:
      Sixty-eight term-pregnant women (before labor 18, in normal labor 16, uterine
      inertia 34) were enrolled for study. Serum and AF E2, E3, Po, Co, hPL
      concentrations were measured by radioimmunoassay in 56 out of the 68 subjects.
      Myometrium gap junction (GJ), dense body (DB), sarcoplasmic reticulum (SR) were
      observed under electron microscope in the remaining 12 subjects (before labor 6,
      Uterine inertia 6). RESULTS: (1) E2, E3 levels and E2/Po, E3/Po ratio in AF, but
      not in serum, increased successively in the groups before labor, in normal labor
      and uterine inertia with significant differences (P < 0.01). (2) Both serum and
      AF Co, hPL concentrations were significantly different before and during labor (P
      < 0.01, P < 0.05). (3) Serum E2, E3, Co and hPL levels elevated significantly in
      cases with uterine inertia after successful treatment with estradiol benzoate or
      oxytocin infusion. (4) Compared with the group before labor, the amount of
      myometrium GJ, DB, SR increased significantly after the onset of labor.
      CONCLUSIONS: The elevation of serum and AF Co, hPL concentrations may be involved
      in the initiation of labor. This may be one of the major factors affecting the
      uterine contractions. Appropriate serum and AF estrogen (E), progestin (P), E/P
      ratio may be related to normality of uterine contractions during labor. The
      increase of GJ, DB, SR amount in uterine myometrium may be the histologic basis
      for the onset of labor.

PMID- 7587575
TI  - [Bone histomorphometry study in post-menopausal women with osteopenia].
AB  - OBJECTIVES: To investigate the histological features of bone, the turnover status
      of bone remodeling in postmenopausal women with osteopenia. To observe the
      influence of age on the changes of bone turnover. METHODS: Two hundred ninety
      three bone biopsies were obtained from posterior iliac crests of postmenopausal
      white women with osteopenia after taking fluorescence-labelled tetracyclin. All
      these specimens were embedded in methacrylate, the nondecalcified sections were
      stained routinely and measured by computerized histomorphometry. RESULTS: The
      mean trabecular bone volume was 10.6% +/- 5.47%, which is 29.3% less than the low
      limit of normal range (15%) established in our laboratory. There were 186 cases
      (63.5%) in normal turnover status, 75 cases (25.6%) in high turnover, and 32
      cases (10.9%) in low turnover. In comparison with the normal turnover group, the
      osteoclast number, corrected bone mineralization rate and bone formation rate
      were elevated and mineralization lag time was reduced in the high turnover group
      (P < 0.01). In contrary, all the above parameters in the low turnover group were
      on the opposite (P < 0.05-0.01). Comparison of three age groups (51-60, 61-70, >
      70 years) showed that the bone volume and osteoid volume decreased as the age
      increased. The proportion of high and low turnover types began to increase in the
      51-60 age group, peaked in the 61-70 age group and dropped to nadir in the > 70
      age group. CONCLUSIONS: Bone histomorphometry examination is not only valuable in
      distinguishing osteoporosis from osteomalacia, but also beneficial for
      determination of the bone turnover status and, therefore, is useful for the
      direction of clinical treatment in patients with postmenopausal osteopenia.

PMID- 7587577
TI  - [Megaloblastic changes in cervical epithelium associated with oral contraceptives
      and changes after treatment with folic acid].
AB  - OBJECTIVE: To study the influence of oral contraceptives on cervical epithelium,
      serum and red blood cell folate levels of users and to observe the changes after
      treatment with folic acid. METHODS: Morphology of cervical epithelium, serum
      folate and red blood cell folate levels were studied in 101 women who had used
      oral contraceptives for over 6 months and 33 intrauterine devices users served as
      controls, 29 women using oral contraceptives with cervical megaloblastic changes
      were treated with folic acid (5mg daily) for 3-4 weeks and followed up for
      observation on morphological changes of cervical epithelium. RESULTS: The mean
      nuclear diameter of cervical epithelial cells was larger in the oral
      contraceptive group than that in the control group (P < 0.001). Megaloblastic
      changes in cervical epithelium occurred in 29 women in the oral contraceptive
      group (28.7%). There was significant difference in the occurrence of cervical
      megaloblastic changes between the two groups (P < 0.01). The level of red blood
      cell folate was lower in the oral contraceptive group than that in the control
      group (P < 0.05). There was no difference in serum folate, hemoglobin and
      neutrophil nuclear index between the two groups (P > 0.05). The mean nuclear
      diameter of cervical epithelial cells decreased significantly (P < 0.001) and
      multinuclear and vacuolar changes disappeared after folic acid therapy in 26
      women with megaloblastic changes. CONCLUSIONS: Oral contraceptives reduced folate
      storage in the body and resulted in megaloblastic changes in cervical epithelium.
      This condition was improved with folic acid therapy.

PMID- 7587576
TI  - [Amplification of proto-oncogenes C-myc, C-N-ras, C-Ki-ras, C-erbB2 in ovarian
      carcinoma].
AB  - OBJECTIVE: To observe the amplification rate of C-myc, C-N-ras, C-Ki-ras, C-erbB2
      in human ovarian carcinoma. METHODS: Southern blot hybridization of DNA was
      employed, pathological diagnosis was made from fresh tissues. The beta-globin
      gene was used as an internal control. RESULTS: The amplification rate of C-myc, C
      N-ras, C-Ki-ras and C-erbB2 in ovarian carcinoma was 50%, 44%, 31% and 25%
      respectively. The amplification rates of C-myc, C-erbB2 in stage III and IV were
      all significantly greater than that in stage I (P < 0.01). The amplification rate
      of C-N-ras in stage I was also significantly greater than that in stage III (P <
      0.01). The amplification rate of C-Ki-ras in stage I was significantly greater
      than that in stage III or IV (P < 0.01). CONCLUSIONS: The amplification of C-Ki
      ras and C-N-ras took place chiefly in cases of the early stages and in cases with
      good differentiation. The amplification of C-N-ras was also found in cases of
      advanced stages. The amplifications of C-myc and C-erbB2 were chiefly found in
      cases above stage III and in cases with poor differentiation, 83% of the patients
      who died were found to have amplifications of more than 2 proto-oncogenes, with
      the amplification of C-erbB2 involved in all of them.

PMID- 7587578
TI  - [Study on the relationship between uterine bleeding with intrauterine device and
      viral infection].
AB  - OBJECTIVE: To study the relationship between uterine bleeding with intrauterine
      device (IUD) and virus infection. METHODS: Virus isolation from endometrium
      samples both with IUD and without IUD was performed with rabbit kidney cell. The
      cell pathogen effect (CPE) directed the positive isolation. All isolated viruses
      were further identified by polymerase chain reaction (PCR) for human
      cytomegalovirus (HCMV) and by neutralizing test for herpes simplex virus type II
      (HSV-II). RESULTS: The endometrial samples were obtained from four groups: 113
      patients with uterine bleeding with IUD; 109 healthy women, without uterine
      bleeding with IUD; 24 healthy women without IUD and 11 patients with uterine
      bleeding without IUD. The rates of virus isolation in four groups mentioned above
      were 59.29%, 19.27%, 16.67% and 63.64% respectively. The positive rates for HCMV
      and HSV-II in the four groups were 38.81%, 19.05%, 1/4, 3/7 and 23.88%, 23.87%,
      1/4, 0.00% respectively. The unidentified viruses were 37.31%, 57.14%, 2/4 and
      4/7 respectively. CONCLUSIONS: These results showed that some endometrial samples
      from both the bleeding groups and the controls were infected by HCMV and HSV-II.
      The incidence of virus infection in women with uterine bleeding with IUD was much
      higher than that of the controls, but similar to that is the patients with
      uterine bleeding without IUD. The results suggested that IUD could activate
      latent viruses (HCMV, HSV-II) infection and induce bleeding in certain
      conditions.

PMID- 7587579
TI  - [Uses of interventional arteriographic technics in gynecologic neoplasms].

PMID- 7587581
TI  - An Mr 51,000 protein of mammalian spermatogenic cells that is common to the whole
      XY body and centromeric heterochromatin of autosomes.
AB  - During mammalian male meiotic prophase the sex chromosomes form a structure
      called the XY body or sex vesicle. This structure is characterized by
      differential condensation of chromatin and transcriptional inactivity. The
      reasons and mechanisms for the allocyclic behaviour of sex chromosomes with
      respect to autosomes are largely unknown. In order to gain insight into the
      process of XY-body formation we are involved in the characterization of proteins
      associated with meiotic sex chromosomes by immunological approaches. Here we
      report on the identification of an Mr 51,000 protein (p51) that is homogeneously
      distributed in the XY body of rodents as shown by immunocytochemistry with the
      novel monoclonal antibody 4EC. Interestingly, in germ line cells the antibody
      also labelled the centromeric heterochromatin of autosomes. We speculate that p51
      may be a component of the mechanisms that lead to wide chromosome regions
      becoming inaccessible for transcription and/or recombination events.

PMID- 7587580
TI  - Well-defined genome architecture in the human sperm nucleus.
AB  - Using fluorescence in situ hybridization, conventional epifluorescence
      microscopy, and laser scanning confocal microscopy followed by three-dimensional
      reconstruction we describe a well-defined higher order packaging of the human
      genome in the sperm cell nucleus. This was determined by the spatial localization
      of centromere and telomere regions of all chromosomes and supported by
      localization of subtelomere sequences of chromosome 3 and the entire chromosome
      2. The nuclear architecture in the human sperm is characterized by the clustering
      of the 23 centromeres into a compact chromocenter positioned well inside the
      nucleus. The ends of the chromosomes are exposed to the nuclear periphery where
      both the subtelomere and the telomere sequences of the chromosome arms are joined
      into dimers. Thus chromosomes in the human sperm nucleus are looped into a
      hairpin-like configuration. The biological implications of this nuclear
      architecture in spermatogenesis and male pronuclear formation following
      fertilization are discussed.

PMID- 7587583
TI  - Extrachromosomal amplification of rDNA in oocytes of Hemerobius spp. (Insecta,
      Neuroptera).
AB  - In previtellogenic oocytes of the neuropteran, Hemerobius spp., two distinct, DNA
      positive intranuclear structures have been observed. Chromosomes of meiotic
      prophase assemble in the center of the oocyte nucleus forming a highly
      polymorphic karyosphere, which persists in this position until the very late
      stages of vitellogenesis. The extrachromosomal DNA body, containing amplified
      ribosomal genes, undergoes fragmentation and dispersion in the nucleoplasm. At
      the onset of previtellogenic growth, transcription of extra rDNA starts, which is
      accompanied by the appearance of dense, granular material (multiple nucleoli).
      Arising nucleoli gradually fill the nucleoplasm. At the electron microscopic (EM)
      level two electron dense structural forms of the granular material have been
      described. Together with general histological and ultrastructural analysis the
      amplification of rDNA genes in Hemerobius spp. oocytes has been demonstrated by
      means of the spreading technique, which has shown that extra rDNA is organized in
      rings containing various numbers of active ribosomal genes. The transcription
      activity of amplified genes is manifested in the form of typical "Christmas tree"
      structures.

PMID- 7587582
TI  - Autonomous replication in Drosophila melanogaster tissue culture cells.
AB  - This study addresses the ability of DNA fragments from various sources to mediate
      autonomous DNA replication in cultured Drosophila melanogaster cells. We created
      a series of plasmids containing genomic DNA fragments from the Ultrabithorax gene
      of Drosophila and test ed them for autonomous replication after transfection into
      Schneider line 2 cells. We found that all plasmids containing Drosophila DNA were
      able to replicate autonomously, as were random human and Escherichia coli genomic
      DNA fragments. Most of the plasmids were detectable 18 days after transfection in
      the absence of selection, suggesting that transfected DNA is maintained in
      Drosophila cells without rapid loss or degradation. The finding that all plasmids
      containing Drosophila, human or bacterial DNA replicate autonomously in
      Drosophila cells suggests that the signals that direct autonomous replication in
      Drosophila contain a low degree of sequence specificity. A two-dimensional gel
      analysis of initiation on one of the plasmids was consistent with many dispersed
      initiation sites. Low sequence specificity and dispersed initiation sites also
      characterize autonomous replication in human cells and Xenopus eggs and may be
      general properties of autonomous replication in animal cells.

PMID- 7587584
TI  - Molecular characterization of the zerknullt region of the Antennapedia complex of
      D. subobscura.
AB  - We have characterized at the molecular level the zerknullt (zen) region of the
      Drosophila subobscura Antennapedia complex. The sequence comparison between D.
      subobscura and D. melanogaster shows an irregular distribution of the conserved
      and diverged regions, with the homeobox and a putative activating domain
      completely conserved. Comparisons of the promoter sequence and pattern of
      expression of the gene during development suggest that the regulation of zen has
      been conserved during evolution. The conservation of zen expression in a
      subpopulation of the polar cells indicates the existence of an important role in
      such cells. We describe a transitory segmented pattern of expression of zen in
      both species, suggesting the existence of interactions with a pair rule gene.
      Some indirect clues indicate that the z2 gene might be absent from the D.
      subobscura genome. A chromosome walk initiated to reach the proboscipedia gene of
      D. subobscura reveals that the distance between pb and zen is at least four times
      the one described for D. melanogaster and for D. pseudoobscura. Finally, we
      present cytological evidence showing that the ANT-C is inverted in D. subobscura
      as compared to D. melanogaster.

PMID- 7587585
TI  - Subnucleolar location of fibrillarin and variation in its levels during the cell
      cycle and during differentiation of plant cells.
AB  - The nucleolar protein fibrillarin has been studied in onion cells; it is detected
      as an M(r) 37,000 protein by immunoblotting using a human autoimmune serum.
      Quantitative immunoelectron microscopy showed that most fibrillarin is localized
      in the transition zone between the fibrillar center (FC) and the dense fibrillar
      component (DFC) as well as in the proximal zone of the DFC, where the labeling
      shows a gradual decrease outward until it reaches insignificant levels in the
      distal zone of the DFC. Thus, fibrillarin is not uniformly distributed throughout
      the DFC of plant cells. This result supports the hypothesis that the
      morphologically homogeneous DFC may not be uniform in function; it is also in
      agreement with the hypothesized vectorial flow of ribosome biogenesis through the
      same compartments. Data are also presented showing that the amount of fibrillarin
      increases when nucleolar activity increases in G2, and probably decreases when
      nucleolar activity decreases during differentiation.

PMID- 7587586
TI  - The chlorarachniophyte: a cell with two different nuclei and two different
      telomeres.
AB  - Chlorarachniophyte algae contain a complex chloroplast derived from the
      endosymbiosis of a eukaryotic alga. The reduced nucleus of the endosymbiont, the
      nucleomorph, is located between the inner and outer pair of membranes surrounding
      the chloroplast. The nucleomorph of chlorarachniophytes has previously been
      demonstrated to contain at least three small linear chromosomes. Here we describe
      cloning the end of the smallest nucleomorph chromosome which is shown to carry a
      telomere consisting of a tandemly repeated 7 bp sequence, TCTAGGG. Using the
      telomere repeat as a probe, we show that nucleomorph telomeres display typical
      hetero-disperse size distribution. The nucleomorph is shown to contain only three
      chromosomes with a haploid genome size of just 380 kb. All six nucleomorph
      chromosome termini are identical with an rRNA cistron closely linked to the
      telomere. The nucleomorph chromosomes thus have relatively large inverted repeats
      at their ends. Chromosomes from the host nucleus are shown to have a different
      telomere repeat motif to that of the nucleomorph chromosomes.

PMID- 7587587
TI  - A comparative study of karyotypes of muntjacs by chromosome painting.
AB  - We have used a combination of chromosome sorting, degenerate oligonucleotide
      primed polymerase chain reaction (DOP-PCR), chromosome painting and digital image
      capturing and processing techniques for comparative chromosome analysis of
      members of the genus Muntiacus. Chromosome-specific "paints" from a female Indian
      muntjac were hybridised to the metaphase chromosomes of the Gongshan, Black, and
      Chinese muntjac by both single and three colour chromosome painting. Karyotypes
      and idiograms for the Indian, Gongshan, Black and Chinese muntjac were
      constructed, based on enhanced 4', 6-diamidino-2-phenylindole (DAPI) banding
      patterns. The hybridisation signal for each paint was assigned to specific bands
      or chromosomes for all of the above muntjac species. The interspecific
      chromosomal homology was demonstrated by the use of both enhanced DAPI banding
      and comparative chromosome painting. These results provide direct molecular
      cytogenetic evidence for the tandem fusion theory of the chromosome evolution of
      muntjac species.

PMID- 7587589
TI  - FISH analysis of the telomere sequences of bulldog ants (Myrmecia: formicidae).
AB  - Chromosomes from several species of ants from the genus Myrmecia were hybridized
      with deoxyoligomer probes of either (T2AG2)7, the putative insect telomere repeat
      sequence, or (T2AG3)7, the vertebrate telomere repeat sequence. While both
      sequences hybridized over a range of stringency conditions, (T2AG2)n was clearly
      the predominant sequence at the termini of the Myrmecia chromosomes. No
      interstitial sites of either sequence were detected. The genus Myrmecia has a
      wide range of karyotypes, with chromosome numbers ranging from 2n=2-84. It has
      been hypothesized that the ancestral karyotype was 2n=4 and karyotype evolution
      proceeded with an increase in chromosome number. In the absence of detectable
      interstitial sites of telomere sequence, it is interesting to speculate on the
      origin of the new telomeres as the chromosome numbers increased.

PMID- 7587588
TI  - Diheteroduplex formation using gold labeled single-stranded PCR fragments and its
      application in electron microscopy.
AB  - Heteroduplex analysis is commonly used to map homologous sequences in DNA:DNA or
      DNA:RNA hybrids in spread preparations by electron microscopy. However, the
      standard procedures are not suitable to detect the orientation of a fragment with
      a defined sequence in a hybrid molecule. Here, we describe an alternative
      protocol for the visualization of DNA:DNA "diheteroduplex" structures based on
      digoxigenin/anti-digoxigenin gold labeling that allows determination of the
      position and orientation of a fragment. Single-stranded polymerase chain reaction
      (PCR) generated fragments labeled at their 3' ends are hybridized to double
      stranded plasmid DNA. Electron microscopy of spread preparations visualizes the
      gold label and, in combination with morphometric measurements, it is possible to
      determine the position and orientation of the fragment with the diheteroduplex
      molecule.

PMID- 7587593
TI  - Floral chromosomes of Arabidopsis thaliana for detecting low-copy DNA sequences
      by fluorescence in situ hybridization.
AB  - Cosmid and plasmid clones containing 11 kb, or more, of genomic DNA sequences
      were mapped with high efficiencies using fluorescence in situ hybridization
      (FISH) to mitotic metaphase chromosomes prepared from floral tissues of
      Arabidopsis thaliana. The chromosomal locations were correlated with the map
      positions determined by RFLP (restriction fragment length polymorphism) analyses.
      Almost no signals were detected on the chromosomes of root meristematic tissues
      when FISH was performed with the same clones as probes. This discrepancy in
      efficiency of detection is possibly caused by the differences in chromatin
      structure between the root meristematic tissues and the floral tissues.

PMID- 7587592
TI  - A novel minisatellite at a cloned hamster telomere.
AB  - The ends of eukaryotic chromosomes have special properties and roles in
      chromosome behavior. Selection for telomere function in yeast, using a Chinese
      hamster hybrid cell line as the source DNA, generated a stable yeast artificial
      chromosome clone containing 23 kb of DNA adjacent to (TTAGGG)n, the vertebrate
      telomeric repeat. The common repetitive element d(GT)n appeared to be responsible
      for most of the other stable clones. Circular derivatives of the TTAGGG-positive
      clone that could be propagated in E. coli were constructed. These derivatives
      identify a single pair of hamster telomeres by fluorescence in situ
      hybridization. The telomeric repeat tract consists of (TTAGGG)n repeats with
      minor variations, some of which can be cleaved with the restriction enzyme MnlI.
      Blot hybridization with genomic hamster DNA under stringent conditions confirms
      that the TTAGGG tracts are cleaved into small fragments due to the presence of
      this restriction enzyme site, in contrast to mouse telomeres. Additional blocks
      of (TTAGGG)n repeats are found approximately 4-5 kb internally on the clone. The
      terminal region of the clone is dominated by a novel A-T rich 78 bp tandemly
      repeating sequence; the repeat monomer can be subdivided into halves
      distinguished by more or less adherence to the consensus sequence. The sequence
      in genomic DNA has the same tandem organization in probably a single primary
      locus of >20-30 kb and is thus termed a minisatellite.

PMID- 7587595
TI  - A comparative study of orientation at behavior of univalent in living grasshopper
      spermatocytes.
AB  - Orientational movements and modes of segregation at anaphase I were analyzed in
      three different types of univalents in living spermatocytes of the grasshopper
      species Eyprepocnemis plorans, namely the sex univalent, three types of accessory
      chromosomes and spontaneous and induced autosomal univalents. When two or more
      univalents were present in the same spindle, their dynamics were directly
      compared. Chromosomes may show variable velocity and number of reorientations:
      the X and the most common B types (B1 and B2) are slow and rarely reorient, a
      more geographically restricted B (B5) is faster and reorients more often, and
      autosomal univalents are the fastest and show the highest frequency of
      reorientations. Nonetheless, the X and the accessories are rigorously reductional
      at anaphase I whereas autosomal univalents often fail to migrate or divide
      equationally. This indicates that orientational and segregational behavior are
      controlled mainly by chromosomal rather than cellular characteristics and that
      chromosomes may display a great variety of strategies to achieve regular
      segregation.

PMID- 7587594
TI  - Polytene chromosomes show normal gene activity but some mRNAs are abnormally
      accumulated in the pseudonurse cell nuclei of Drosophila melanogaster otu
      mutants.
AB  - Certain mutant alleles of the ovarian tumor (otu) locus give rise to polytene
      chromosomes in the pseudonurse cells (PNCs). We have previously shown that the
      banding pattern of these germ line-derived chromosomes is similar to that in the
      larval salivary gland chromosomes. In this study, we have examined the gene
      activity of these chromosomes. General gene expression from these chromosomes was
      studied by uridine autoradiography. The expression of specific genes was
      monitored by in situ hybridisation to mRNA and also by combining enhancer trap
      lines with otu mutants. We found that most of the genes studied were expressed in
      the PNCs as they were in the wild-type nurse cells. Four out of the 12 mRNAs
      studied accumulated in the nuclei instead of migrating to the cytoplasm. The
      intensity of accumulation directly correlated with the extent of polytenisation
      in the PNC nuclei. We suggest that the otu mRNA remains partly attached to the
      polytene chromosome template after transcription and discuss the effects of this
      phenomenon on polytenisation of the PNC chromosomes.

PMID- 7587591
TI  - Mechanisms of DNA expansion.
AB  - Unstable transmission of repeating segments in genes is now recognized as a new
      class of mutations causing human disease. Genetic instability observed in disease
      is termed an "expansion mutation" when the mutation is an increase in the copy
      number of a repeated unit, commonly a di- or trinucleotide. While the expansion
      mutation is well characterized in disease, the mechanism by which expansion
      occurs is not clear. This article focuses on physical properties of expansion at
      repeating nucleotides that may provide clues to the mechanism. Both biochemical
      and genetic data indicate that DNA structure is part of the mechanism and the
      underlying cause for expansion.

PMID- 7587596
TI  - [The study of somatotrophic substance for hepatic cells].

PMID- 7587597
TI  - [Gene mutation of hepatitis B virus].

PMID- 7587590
TI  - Dynamic changes in Rad51 distribution on chromatin during meiosis in male and
      female vertebrates.
AB  - Antibodies against human Rad51 protein were used to examine the distribution of
      Rad51 on meiotic chromatin in mouse spermatocytes and oocytes as well as chicken
      oocytes during sequential stages of meiosis. We observed the following dynamic
      changes in distribution of Rad51 during meiosis: (1) in early leptotene nuclei
      there are multiple, apparently randomly distributed, foci that by late leptonema
      become organized into tracks of foci. (2) These foci persist into zygonema, but
      most foci are now localized on Rad51-positive axes that correspond to lateral
      elements of the synaptonemal complex. As homologs synapse foci from homologous
      axes fuse. The distribution and involvement of Rad51 foci as contact points
      between homologs suggest that they may be components to early recombination
      nodules. (3) As pachynema progresses the number of foci drops dramatically; the
      temporal occurrence (mice) and physical and numerical distribution of foci on
      axes (chickens) suggest that they may be a component of late recombination
      nodules. (4) In early pachynema there are numerous Rad51 foci on the single axis
      of the X (mouse spermatocytes) or the Z (chicken oocytes) chromosomes that
      neither pair, nor recombine. (5) In late pachynema in mouse spermatocytes, but
      not oocytes, the Rad51 signal is preferentially enhanced at both ends of all the
      bivalents. As bivalents in spermatocytes, but not oocytes, begin to desynapse at
      diplonema they are often held together at these Rad51-positive termini. These
      observations parallel observations that recombination rates are exceptionally
      high near chromosome ends in male but not female eutherian mammals. (6) From
      diakinesis through metaphase I, Rad51 protein is detected as low-intensity
      fluorescent doublets that localize with CREST-specific antigens (kinetochores),
      suggesting that Rad51 participates, at least as a structural component of the
      materials involved, in sister kinetochore cohesiveness. Finally, the changes in
      Rad51 distribution during meiosis do not appear to be species specific, but
      intrinsic to the meiotic process.

PMID- 7587598
TI  - [Chronic hepatitis: diagnosis, grading and staging].

PMID- 7587600
TI  - [A kinetic study of hepatitis B virus pre-C gene mutation].
AB  - The point mutation in the precore region of hepatitis B viral genome (nt83) was
      tested with the method of mispairing PCR-RFLP in 54 chronic hepatitis B patients
      all confirmed by liver biopsy. The over all detection rate of pre-C mutation was
      66.7% and the detection rate of pre-C mutation in chronic active hepatitis
      patients was as high as 80.0%, being significantly higher than that in chronic
      persistent hepatitis (46.7%). The detection rate of pre-C mutation was 41.2% in
      hepatitis B e antigen (HBeAg) positive group and 63.3% in anti-HBe(+) group
      respectively. The detection rate in anti-HBe(+) patients with normal alanine
      transaminase activity was as high as 82.4%. During the period of follow up it was
      found that pre-C mutation may appear and disappear or may persist continually.
      The results suggested that pre-C mutation was extremely common in chronic
      hepatitis B virus (HBV) infection. The coexistence of the mutant type and wild
      type in the patients may be considered as the natural course of HBV chronic
      infection. Further study on the cause and effect relation between pre-C mutation
      and genesis of chronic active hepatitis and liver cirrhosis is urgently needed.

PMID- 7587599
TI  - [Effects of interferon treatment on mutation of hepatitis B virus precore
      genome].
AB  - Effects of interferon (IFN) treatment on mutation of hepatitis B virus (HBV)
      precore were studied with a rapid polymerase chain reaction method to investigate
      the stop codon in the distal precore region during HBV precore mutation. 6 cases
      of chronic hepatitis B were treated with recombinant IFN alpha 1 3 x 10(6) U/day
      for 14 weeks. In 4 of them HBV DNA was undetectable after treatment. Precore
      mutant was detected in the remaining 2 cases whose HBV DNA was still positive. In
      a group of 11 cases not treated with IFN, mutants were detected in 3. HBV e
      antigen (HBeAg) became negative after IFN treatment in one case, the original
      wild strain was replaced by a status of co-existence of mutant and wild strain.
      These results suggest that HBeAg negative seroconversion after IFN treatment does
      not necessarily implicate a complete clearance of HBV and the possibility of
      mutation of precore still exists.

PMID- 7587601
TI  - [Analysis of hepatitis B virus X antigen expression in chronic hepatitis B and
      cirrhosis].
AB  - It has been shown that hepatitis B virus (HBV) X antigen (HBxAg) functioned as a
      transactivating element which can act on the enhancer of HBV in an in vitro
      system and elevate the transcriptional level of HBV. In this study we investigate
      the relationship between HBxAg expression and HBV replication in patients with
      chronic hepatitis B and cirrhosis. Rabbit IgG against recombinant HBxAg which was
      synthesized in E. coli were prepared and used for the detection of HBxAg. HBV DNA
      was amplified by polymerase chain reaction technique by using primers from HBx
      gene sequence. Liver tissue samples and sera from the patients were examined
      immunohistochemically for HBxAg and serologically for HBxAg/anti-HBx
      respectively. We focused on its expression in these samples in comparison with
      markers of HBV replication. It was found that in liver HBxAg was present in 72.7%
      of the patients with chronic active hapatitis (CAH) and 92.6% of those with
      cirrhosis, while the positivity rate of HBcAg in cirrhosis patients was only
      47.8%. In the sera of the patients with CAH, chronic persistant hepatitis and
      cirrhosis HBxAg was present in 44.4%, 66.6% and 33.3% respectively. It was
      similar to that observed with HBeAg. Moreover in these HBxAg positive sera HBV
      DNA can also be detected. It was shown that higher rate of positivity of HBxAg
      was found in patients with replicative markers (serum HBeAg, serum HBV DNA or
      liver tissue HBcAg positive). Our results indicate that expression of HBxAg is
      closely correlated with HBV replication and HBxAg may be an important marker in
      chronic HBV infection.

PMID- 7587602
TI  - [14C-urea breath test in the diagnosis of Helicobacter pylori infection in the
      stomach].
AB  - We developed a modified 14C-urea breath test (14C-UBT) to diagnose Helicobacter
      pylori (Hp) infection in 70 patients in which subjects were given 92.5 kBq (2.5
      microCi) 14C-urea with 25 mg nonradioactive urea, without nutrient-dense meal.
      Using the mean value +3s as a cutoff value, the 20 min sample gave a sensitivity
      of 97.36%, a specificity of 90.00%, a positive predictive value of 97.36%, and a
      negative predictive value of 90.0%. Our data showed: (1) A satisfying accuracy of
      the modified 14C-UBT for the detection of Hp infection was obtained. (2) Taking
      92.5 kBq (2.5 microCi) 14C-urea and 20 min collected sample may be of great use
      and to replace the previous big dose and long time methods. (3) This test may be
      applied routinely as a noninvasive, accurate, low cost, safe and rapid method.
      (4) It played an important role in reflecting the susceptibility of Hp to various
      drugs in vivo and monitoring the recurence of Hp.

PMID- 7587603
TI  - [Amplifying Helicobacter pylori's urease gene by nested polymerase chain
      reaction].
AB  - By using nested polymerase chain reaction (PCR) composed of three primers that
      derived from Helicobacter pylori's (Hp) urease gene region, we have not only
      successfully amplified control Hp and 214 clinic samples but also studied deeply
      preparation of the sample, composition of PCR reaction liquid and circulatory
      mental conditions of the PCR. So this method shortens the operation time,
      simplifies processes and reduces costs. Compared with urease test (54%) and
      Warthin-Starry silver stained test (50%), ever used the positive rate of PCR is
      the highest (61%), so our method is more specific, sensitive, simple, rapid and
      accurate, and could be applied to the routine clinical detection.

PMID- 7587605
TI  - [The effect of hirudo on proteinuria, lipid metabolism and coagulation system in
      the patients with chronic glomerulonephritis].
AB  - Renal biopsy was performed in 31 cases of primary glomerulonephritis and the
      effect of Hirudo in these patients observed. The results revealed that
      proteinuria decreased significantly, serum albumin increased significantly and
      cholesterol, triglyceride reduced significantly 4 weeks after treatment with
      Hirudo (P < 0.01 or P < 0.05); Fibrinogen and platelet aggregation reduced
      significantly (P < 0.01). However, platelet count, partial thromboplastin time,
      bleeding and clotting time did not change (P > 0.05); urine NAGase decreased
      significantly (P < 0.01). It is concluded that Hirudo may decrease proteinuria
      and alleviate renal parenchymal damage.

PMID- 7587607
TI  - [Acute effect of milrinone on pulmonary hemodynamics in patients with hypoxic
      pulmonary hypertension].
AB  - Milrinone is a phosphodiesterase inhibitor that has vasorelaxant activity. The
      authors studied its effect on pulmonary haemodynamics in 12 patients with hypoxic
      pulmonary hypertension. After treatment with milrinone, mean pulmonary arterial
      pressure (from 4.61 +/- 1.41 kPa to 3.36 +/- 1.20 kPa, 1kPa = 7.5mmHg) and
      pulmonary vascular resistance (from 557.56 +/- 167.70 dyne.sec.cm-5 to 392.60 +/-
      133. 81 dyne.sec.cm-5) decreased (P < 0.05), while cardiac output increased (from
      5.11 +/- 1.62 L/min to 5.62 +/- 1.66 L/min) (P > 0.05). The systemic blood
      pressure (from 11.50 +/- 1.63 kPa to 10.71 +/- 1.83 kPa) and systemic vascular
      resistance (from 1476.64 +/- 531.52 dyne.sec.cm-5 to 1,236.49 +/- 410.18
      dyne.sec.cm-5) also decreased (P > 0.05). but there was no change in arterial
      oxygen saturation (SaO2). The incidence of side effects were low, 4 patients
      developed tackycardia, and 2 patients developed ventricular premature beats. It
      is therefore, shown that milrinone is a potent pulmonary vasodilator.

PMID- 7587608
TI  - [A clinical analysis of 15 cases of acute leukemia complicating pregnancy].
AB  - To explore the rational treatment program for acute leukemia complicating
      pregnancy, we carried out a retrospective study of 15 cases of acute leukemia
      complicating pregnancy and treated with chemotherapy from 1973 to 1993 in the
      Hematology Ward of PUMC. Review of the cases receiving chemotherapy revealed no
      harm to the children in cases of late onset and poor prognosis for the children
      in cases of early onset. However, the overall results seemed to indicate that the
      earlier the chemotherapy was instituted, the better the outcome will be for the
      mothers. A protocol is thus proposed with emphasis on the timing of institution
      of chemotherapy in relation to the course of pregnancy. Briefly, induced abortion
      followed by combined chemotherapy in early pregnancy and timely combined
      chemotherapy in mid- and late pregnancy are recommended. Brief cessation of
      chemotherapy during parturition may be necessary and sufficient supportive
      measures are needed.

PMID- 7587604
TI  - [The effectiveness of combined insulin and sulfonylurea in treating non-insulin
      dependent diabetic patients].
AB  - The effectiveness of combined therapy with insulin and sulfonylurea in non
      insulin dependent diabetes mellitus (NIDDM) patients has, for decades, been a
      debated issue. In order to probe this question, we studied 33 diabetes mellitus
      patients aged 40 years and over, having a history of this disease for more than 5
      years, treated with one of the sulfonylureas at maximal dosage for three weeks
      but without effect. These 33 cases were divided into three groups randomly: group
      A: treated with glurenorm and insulin. B insulin and C glurenorm. The treatment
      lasted 4 months. During the course of the trial, estimation of the free-insulin,
      C-peptide, blood glucose etc. was carried out three times i.e. one before the
      trial and then 2, 4 months after the trial. The data were dealed with U-test and
      comparison was made before and after the trial and between the three groups. It
      is shown that combined therapy with sulfonylurea and insulin is effective in
      NIDDM patients, especially in those with secondary failure of beta-cell function
      and the combined therapy may be used in NIDDM patients during the transitional
      period from treatment with sulfonylurea alone to traditional insulin cure.

PMID- 7587606
TI  - [Dynamic observation of alpha-granule membrane protein 140 during the treatment
      of thrombolytic and anticoagulant therapy in patients with acute myocardial
      infarction].
AB  - The degree of platelet activation and damage in 15 cases with acute myocardial
      infarction (AMI) receiving thrombolytic therapy and 15 cases with AMI receiving
      anticoagulant therapy were studied in vivo and in vitro by using specific
      monoclonal antibodies (SZ-51 & S12) against alpha-granule membrane protein 140
      (GMP-140). Clinical indexes and myocardial enzyme changes in the two groups of
      patients were also observed. The results showed that the number of GMP-140
      molecules on platelet surface and the concentration of GMP-140 in plasma were
      increased before treatment. The number of GMP-140 molecules on platelet surface
      began to decrease on the 1st day and returned to baseline on the 7th day after
      treatment. The concentration of GMP-140 in plasma reached a peak on the 1st day,
      began to fall on the 2nd day and returned to baseline on the 3rd day after
      treatment. There were no significant differences in the dynamic changes of number
      of GMP-140 molecules on platelet surface and the concentration of GMP-140 in
      plasma between groups of thrombolytic therapy and anticoagulant therapy. In vitro
      experiment showed that the thrombolytic medicine urokinase neither activated
      platelets nor inhibited platelet activation induced by thrombin. Significantly
      greater reperfusion rate and earlier appearance of CK and CK-MB peaks were found
      in the thrombolytic than in the anticoagulant group. LVEF determined by
      echocardiography, rate of return of ST segments to baseline and alleviation rate
      of chest pain were significantly greater and complications of AMI (ventricular
      fibrillation, left ventricular failure and angina) were less in the group
      receiving thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587610
TI  - [Current studies in the quality of ulcer healing].

PMID- 7587609
TI  - [Detection of pathogenic Entamoeba histolytica DNA in liver abscess aspirates
      with polymerase chain reaction].
AB  - Polymerase chain reaction (PCR) was used to diagnose amebic liver abscess by
      detecting pathogenic Entamoeba histolytica DNA in liver aspirates from patients
      with liver abscess. Oligonucleotide primers specific for gene encoding of the
      30,000 molecule of pathogenic Entamoeba histolytica were used in the test. Liver
      aspirates from 23 cases with amebic liver abscess as evidenced by typical
      clinical findings or very high titres of anti-E. Histolytica antibodies with
      ELISA were found to be positive with PCR. Fourteen control samples (3 cases of
      bacterial liver abscess, 1 of liver cancer and 10 of abscess in other sites) were
      all negative to PCR. The results suggest that PCR is a sensitive and useful
      method for diagnosing amebic liver abscess.

PMID- 7587611
TI  - [Neurocardiogenic syncope].

PMID- 7587613
TI  - Pancreatic calcium waves and secretion.
AB  - Pancreatic acinar cells display stereotypic Ca2+ waves resulting from Ca2+
      release from internal stores during stimulation. The Ca2+ waves are initiated at
      the luminal pole, and, at high agonist concentrations, spread towards the basal
      pole. Two key mechanisms behind the generation of Ca2+ waves have been
      identified. First, the Ca2+ waves are composite, mediated by three distinct Ca2+
      release mechanisms with a polarized distribution: high-sensitivity inositol 1,4,5
      trisphosphate (InsP3) receptors at a small trigger zone (T zone) in the secretory
      granule area, Ca(2+)-induced Ca2+ release channels in the granular area and low
      sensitivity InsP3 receptors in the basal area. Second, InsP3 can readily diffuse
      in the cytosol, whereas rises in cytosolic Ca2+ concentration ([Ca2+]i) can be
      confined through strong buffering and sequestration of Ca2+. InsP3 is thus used
      as a long-range messenger to transmit agonist signals to the T zone, and [Ca2+]i
      rises at the T zone are used as a local switch. These mechanisms enable
      preferential activation of the T zone, irrespective of localization of stimuli
      and agonist receptors. The secretion of enzymes and fluid is a direct consequence
      of [Ca2+]i rises at the T zone. The Ca2+ waves and oscillations probably boost
      the T zone functions.

PMID- 7587612
TI  - Calcium waves, gradients and oscillations. Proceedings of a symposium. London, 26
      28 April 1994.

PMID- 7587614
TI  - Calcium signalling during chemotaxis.
AB  - The role of Ca2+ in chemotaxis of eosinophils from the newt Taricha granulosa was
      investigated using fluorescent indicators and digital imaging microscopy. In
      response to serum chemoattractant, cytoplasmic Ca2+ concentration ([Ca2+]i) rises
      prior to polarization. In polarized locomoting cells [Ca2+]i gradients (tail-high
      front-low) are always seen, and when cells turn [Ca2+]i rises transiently and
      falls fastest and furthest in the new direction of cell motion. These Ca2+
      signals, which are required for polarization and locomotion, arise from Ca2+
      derived from internal stores released in response to inositol 1,4,5-trisphosphate
      (InsP3) (because microinjected heparin fully blocks them). 1,2-Diacyl-sn-glycerol
      (DAG), which is co-produced with InsP3, has an inhibitory effect on Ca2+ signals,
      an effect apparently mediated by protein kinase C. Studies with caged InsP3
      reveal that InsP3-responsive stores appear to be concentrated in the nuclear and
      microtubule-organizing centre regions and that InsP3 moves so rapidly within the
      cell that it is effectively a global secondary messenger. Thus, stable [Ca2+]
      gradients observed during unidirectional migration appear to result from the
      concentration of InsP3-responsive Ca2+ stores in the rear of the cell. By
      contrast, we propose that reorientation of the [Ca2+] gradient prior to a change
      in direction of motion results from the joint actions of InsP3 and DAG, with
      InsP3 acting as a global secondary messenger stimulating Ca2+ release and DAG,
      through protein kinase C, acting as a spatially restricted secondary messenger
      inhibiting [Ca2+] increases locally near the site of chemotactic stimulation.

PMID- 7587615
TI  - Calcium signalling in cardiac muscle cells.
AB  - In heart cells, several distinct kinds of transient spatial patterns of
      cytoplasmic calcium ion concentration ([Ca2+]i) can be observed: (1) [Ca2+]i
      waves, in which regions of spontaneously increased [Ca2+]i propagate at high
      velocity (100 microns/s) through the cell; (2) Ca2+ 'sparks', which are
      spontaneous, non-propagating changes in [Ca2+]i that are localized in small
      (approximately 2 microns) subcellular regions; and (3) evoked [Ca2+]i transients
      that are elicited by electrical depolarization, in association with normal
      excitation-contraction (E-C) coupling. In confocal [Ca2+]i images, evoked [Ca2+]i
      transients appear to be nearly spatially uniform throughout the cell, except
      during their rising phase or during small depolarizations. In contrast to [Ca2+]i
      waves and spontaneous Ca2+ sparks, evoked [Ca2+]i transients are triggered by L
      type Ca2+ channel current and they are 'controlled', in the sense that stopping
      the L-type Ca2+ current stops them. Despite their different characteristics, all
      three types of Ca2+ transient involve Ca(2+)-induced release of Ca2+ from the
      sarcoplasmic reticulum. Here, we address the question of how the autocatalytic
      process of Ca(2+)-induced Ca2+ release, which can easily be understood to
      underlie spontaneous regenerative ('uncontrolled'), propagating [Ca2+]i waves,
      might be 'harnessed', under other circumstances, to produce controlled changes in
      [Ca2+]i, as during normal excitation-contraction coupling, or changes in [Ca2+]i
      that do not propagate. We discuss our observations of Ca2+ waves, Ca2+ sparks and
      normal Ca2+ transients in heart cells and review our results on the 'gain' of
      Ca(2+)-induced Ca2+ release. We discuss a model involving Ca2+ microdomains
      beneath L-type Ca2+ channels, and clusters of Ca(2+)-activated Ca2+ release
      channels in the sarcoplasmic reticulum which may form the basis of the answer to
      this question.

PMID- 7587616
TI  - Intercellular calcium waves mediated by inositol trisphosphate.
AB  - Intercellular calcium waves occur in diverse cells. Those that are induced by
      mechanical stimulation have been extensively investigated in epithelial and glial
      cells. Mechanical stimulation of an individual cell initiates an increase in the
      intracellular free calcium concentration, [Ca2+]i, that spreads across the cell.
      At the cell border this intracellular Ca2+ wave is arrested but, after a brief
      delay, similar Ca2+ waves occur in adjacent cells. The repetition of this process
      results in the propagation of an intercellular Ca2+ wave through a limited number
      of cells. The propagation of intercellular Ca2+ waves correlates with the
      presence of functional gap junctions and occurs in the absence of extracellular
      Ca2+ or following the microinjection of inositol 1,4,5-trisphosphate (InsP3). The
      propagation of intercellular Ca2+ waves is inhibited by heparin (an InsP3
      receptor antagonist) and by U73122 (a phospholipase C inhibitor) or when
      intracellular Ca2+ stores are depleted with thapsigargin. These characteristics
      suggest that mechanical stimulation initiates InsP3 production and that
      intercellular Ca2+ waves are propagated through the movement of InsP3 through gap
      junctions. Mathematical modelling supports the idea that diffusion of InsP3 is a
      viable hypothesis for the generation of intercellular Ca2+ waves. The ability of
      cells to display changes in [Ca2+]i that are independent of neighbouring cells
      (i.e., asynchronous Ca2+ oscillations) and the low diffusion constant of Ca2+
      suggest that Ca2+ itself is not a major messenger moving between cells to
      propagate Ca2+ waves.

PMID- 7587617
TI  - Subcellular organization of calcium signalling in hepatocytes and the intact
      liver.
AB  - Hepatocytes respond to inositol 1,4,5-trisphosphate (InsP3)-linked agonists with
      frequency-modulated oscillations in the intracellular free calcium concentration
      ([Ca2+]i), that occur as waves propagating from a specific origin within each
      cell. The subcellular distribution and functional organization of InsP3-sensitive
      Ca2+ pools has been investigated, in both intact and permeabilized cells, by
      fluorescence imaging of dyes which can be used to monitor luminal Ca2+ content
      and InsP3-activated ion permeability in a spatially resolved manner. The Ca2+
      stores behave as a luminally continuous system distributed throughout the
      cytoplasm. The structure of the stores, an important determinant of their
      function, is controlled by the cytoskeleton and can be modulated in a guanine
      nucleotide-dependent manner. The nuclear matrix is devoid of Ca2+ stores, but
      Ca2+ waves in the intact cell propagate through this compartment. The
      organization of [Ca2+]i signals has also been investigated in the perfused liver.
      Frequency-modulated [Ca2+]i oscillations are still observed at the single cell
      level, with similar properties to those in the isolated hepatocyte. The [Ca2+]i
      oscillations propagate between cells in the intact liver, leading to the
      synchronization of [Ca2+]i signals across part or all of each hepatic lobule.

PMID- 7587619
TI  - Calcium oscillations in neurons.
AB  - Oscillations in the cytosolic free Ca2+ concentration ([Ca2+]i) have been
      described in a variety of cells. In some cases, [Ca2+]i oscillations reflect
      cycles of membrane depolarization and voltage-dependent Ca2+ entry. In others,
      they are caused by periodic Ca2+ uptake and release by internal stores, with
      little immediate requirement for external Ca2+. A third type of [Ca2+]i
      oscillation is typified by caffeine-induced oscillations in sympathetic neurons.
      Here, the oscillations depend on the interplay between Ca2+ transport across the
      plasma membrane and transport by a caffeine-sensitive store. These oscillations
      can occur at a steady membrane potential and are blocked by ryanodine (1 microM),
      indicating that they do not result from voltage-dependent changes in Ca2+ entry
      but do require Ca(2+)-induced Ca2+ release. Entry of Ca2+ from the external
      medium is important during all phases of the oscillatory cycle except the rapid
      upstroke, which is dominated by Ca2+ release from an internal store. It is
      proposed that caffeine-induced [Ca2+]i oscillations are cyclic perturbations of
      [Ca2+]i caused by exchange of Ca2+ between the cytosol and the caffeine-sensitive
      store: net Ca2+ loss from the store increases [Ca2+]i transiently above its
      steady-state value ([Ca2+]ss), whereas net accumulation of Ca2+ by the store
      transiently depresses [Ca2+]i below [Ca2+]ss. The effects of rapid removal of
      Ca2+ and caffeine on the rate of change of [Ca2+]i (d[Ca2+]i/dt) provide
      estimates of the rates of net Ca2+ entry and (caffeine-sensitive) Ca2+ release
      and information on the way these rates vary during the oscillatory cycle.

PMID- 7587620
TI  - Calcium signalling during mammalian fertilization.
AB  - The fertilized mammalian egg is a nice model system for analysing spatiotemporal
      Ca2+ signalling in the intact cell. Hamster eggs show repetitive Ca2+ transients,
      associated in the initial response with Ca2+ waves which begin from the site of
      sperm attachment and are propagated across the deep cytoplasm to the opposite
      pole. In unfertilized eggs, a regenerative Ca2+ wave is induced by injection of
      either inositol 1,4,5-trisphosphate (InsP3) or Ca2+, and Ca2+ oscillations are
      produced by continuous injection of InsP3. These Ca2+ waves and oscillations in
      both fertilized and unfertilized eggs are inhibited in a dose-dependent manner by
      a monoclonal antibody to the type 1 InsP3 receptor. Ryanodine receptors (both
      skeletal and cardiac types) are not detected by physiological or immunoblot
      analyses. Positive and negative feedback between cytosolic Ca2+ and Ca2+ release
      from InsP3-sensitive pools accounts for the spatiotemporal Ca2+ signalling. In
      addition to intracellular Ca2+ release, Ca2+ entry from outside the egg is
      necessary to refill the Ca2+ pools and maintain Ca2+ oscillations. Evidence
      suggests that inositol 1,3,4,5-tetrakisphosphate activates the Ca2+ influx. The
      signal transduction process leading to the production of InsP3 and the mechanism
      of egg activation following the Ca2+ response still remain to be elucidated.

PMID- 7587618
TI  - The triggering of astrocytic calcium waves by NMDA-induced neuronal activation.
AB  - It has been well established that astrocytes possess functional receptors for the
      excitatory neurotransmitter glutamate and respond to physiological concentrations
      of this substance with oscillations in cytoplasmic Ca2+ concentrations and
      spatially propagating Ca2+ waves. These findings strongly suggest that glutamate
      released during synaptic transmission triggers such phenomena within the
      perisynaptic astrocyte in situ. We test this hypothesis in two preparations, the
      organotypic hippocampal slice and hippocampal neuron-astrocyte co-cultures, using
      the Ca2+ indicator fluo-3 and confocal laser microscopy. An agonist for the N
      methyl-D-aspartate (NMDA)-preferring glutamate receptor is employed to stimulate
      neuronal populations specifically, leaving the astrocytic population unaffected
      as these cells appear to lack this glutamate receptor subtype. Such
      pharmacological stimulation initially elicits large Ca2+ transients within the
      neuronal populations, followed by Ca2+ spikes in surrounding astrocytes,
      presumably as the result of neuronal glutamate release. During continuous
      neuronal stimulation, the astrocyte's Ca2+ response becomes oscillatory, with a
      period averaging 33 s and ranging from 15 to 50 s at 21 degrees C. These findings
      establish another form of communication within the brain, that between neurons
      and astrocytes, which perhaps acts to couple astrocytic regulatory responses to
      neuronal activity.

PMID- 7587624
TI  - Spiral calcium waves: implications for signalling.
AB  - Spiral patterns of intracellular Ca2+ release demonstrate a direct relationship
      between increasing wavefront curvature and increasing propagation velocity. An
      equally important phenomenon is the annihilation of colliding Ca2+ waves, which
      reveals an underlying refractory period during which further Ca2+ release is
      temporarily inhibited. Treatment of intracellular Ca2+ release as an excitable
      medium accounts for both observations. This theoretical framework is analogous to
      the more familiar concept of electrical excitability in neuronal membranes. In
      this analogy, the inositol 1,4,5-trisphosphate receptor ion channel plays a role
      analogous to that of Na+ channels while Ca(2+)-induced Ca2+ release provides the
      mechanism for excitation. Furthermore, Ca(2+)-ATPases play a role similar to that
      of the K+ channels in neuronal excitation, that is, they return the system to
      rest. We demonstrated that overexpression of a sarco/endoplasmic reticulum Ca(2+)
      ATPase increases the frequency of Ca2+ wave activity. More recent experiments
      reveal a strong dependence of the propagation velocity on wavelength as predicted
      by the dispersion relation of excitability. This important result accounts for an
      observed correlation between wave frequency and spatial dominance of Ca2+ foci
      and suggests a new mechanism for the encoding of signal information.

PMID- 7587621
TI  - Regulation of nuclear calcium concentration.
AB  - Transient increases in nuclear calcium concentration have been shown to activate
      gene expression and other nuclear processes. It has been suggested that nuclear
      calcium signals are controlled by a mechanism that is independent of calcium
      signalling in the cytosol. This would be possible if calcium diffusion is slow
      and a separate calcium release mechanism is localized to the nuclear region.
      Alternatively, the nuclear envelope could act as a diffusion barrier for calcium
      ions released either inside or outside the nucleus. It has also been proposed
      that inositol 1,4,5-trisphosphate (InsP3) can be generated inside the nucleus and
      that there are calcium release channels in the inner membrane of the nuclear
      envelope. Most of the experimental evidence supporting these hypotheses is based
      on the calibration of nuclear and cytosolic calcium concentrations. However,
      recent studies suggest that the local calibration of calcium indicators may not
      be accurate. We propose that nuclear calcium signals can be investigated by a
      different approach that does not rely on accurate calibration of indicators. We
      have developed calcium indicators that minimize facilitated calcium diffusion and
      are localized to either the nucleus or the cytosol. Using the diffusion
      coefficient of calcium ions, and measuring the delay between cytosolic and
      nuclear calcium increases, we show that the nuclear envelope is not a substantial
      barrier for calcium ions in PC12 (phaeochromocytoma) cells. This suggests that
      nuclear and cytosolic calcium signals equilibrate rapidly in these cells.

PMID- 7587623
TI  - Calcium puffs in Xenopus oocytes.
AB  - The second messenger inositol 1,4,5-trisphosphate (InsP3) functions in large part
      by liberating calcium ions from intracellular stores. This release process is
      highly non-linear and shows a regenerative characteristic that allows production
      of all-or-none calcium spikes which propagate as waves. However, at low
      concentrations of InsP3 an additional mode of calcium liberation is seen in
      Xenopus oocytes, transient 'puffs' of cytosolic calcium that last for a few
      hundred milliseconds and are restricted to within a few micrometres. Puffs are
      generally of similar size and the amount of calcium released (about 3 x 10(-18)
      mol) suggests that they arise through the concerted opening of several InsP3
      gated calcium release channels. Puff sites are present at a density of about one
      per 30 microns 2 in the animal hemisphere of the oocyte. Each site functions
      autonomously, producing puffs at largely random intervals. We conclude that
      calcium puffs represent 'quantal' units of InsP3-evoked calcium liberation, which
      may result from local regenerative feedback by cytosolic calcium ions at
      functionally discrete release sites.

PMID- 7587622
TI  - Calcium waves and development.
AB  - Those calcium oscillations which go deep into cells take the form of 'fast'
      calcium waves. In fully active cells at room temperature, these move at 15-30
      microns/s and are propagated by a reaction-diffusion mechanism governed by the
      Luther equation in which calcium ions are the only propagators and calcium
      induced calcium release is the only reaction. However, they may be initiated by a
      second mode of Ca(2+)-induced Ca2+ release within the lumen of the endoplasmic
      reticulum (ER). In sea urchin fertilization, this second mode of Ca(2+)-induced
      Ca2+ release is in turn begun by calcium entering the sperm and thence the ER.
      Subsurface calcium waves include an important class of surface contraction waves
      which move at 0.3-3 microns/s and are called 'slow' waves. Their prototype is the
      0.5 micron/s wave which accompanies and controls cytokinesis in large eggs. Slow
      waves may be propagated by mechanical tension rather than by diffusion. Recent
      work with Dictyostelium transfected with apoaequorin has provided the first views
      of free calcium patterns within a developing, multicellular organism. During most
      or all of development, those regions which will differentiate into stalk or stalk
      like cells (as opposed to spores) exhibit frequent calcium pulses. These pulses
      are believed to be fast calcium waves and to feed back on these regions so as to
      favour non-spore differentiation.

PMID- 7587626
TI  - Cell adhesion and human disease. Chairman's introduction.

PMID- 7587625
TI  - Local calcium spiking in pancreatic acinar cells.
AB  - A few years ago, my laboratory obtained evidence for local agonist-evoked
      repetitive Ca2+ spikes in single pancreatic acinar cells. We have now confirmed
      this and shown that regular cytosolic Ca2+ spikes evoked by low concentrations of
      acetylcholine or inositol 1,4,5-trisphosphate (InsP3) are confined to the
      secretory granule area at the luminal pole of the cells. The local subcellular
      signals probably arise because the first internal messenger (InsP3), generated
      from the basolateral membrane, can diffuse rapidly, whereas the Ca2+ released
      from the more responsive secretory granule region has a very restricted mobility.
      Local Ca2+ spikes are useful from an energetic point of view and also help to
      avoid undesirable activation of Ca(2+)-dependent processes. Another messenger,
      cyclic ADP-ribose, may also regulate intracellular Ca2+ release. In pancreatic
      acinar cells cyclic ADP-ribose induces repetitive Ca2+ spikes localized in the
      secretory granule area; these spikes are blocked by ryanodine, but also by the
      InsP3 receptor antagonist heparin. Ryanodine abolishes or markedly inhibits
      agonist-evoked Ca2+ spiking, but enhances the frequency of spikes evoked by
      internal InsP3 application. These results indicate that both ryanodine and InsP3
      receptors are involved in Ca2+ spike generation in pancreatic acinar cells, and
      that both InsP3 and cyclic ADP-ribose may act as internal messengers.

PMID- 7587633
TI  - P-selectin knockout: a mouse model for various human diseases.
AB  - P-selectin is a transmembrane adhesion receptor specific to platelets and
      endothelial cells. It has an N-terminal lectin domain that recognizes specific
      carbohydrate moieties on monocytes, neutrophils and some other subsets of
      leukocytes. P-selectin is stored in granules and is expressed on the plasma
      membrane only after the cells are stimulated by vascular injury or during
      inflammation. Physiologically P-selectin is likely to be involved in the
      recruitment of leukocytes that promote wound healing and fight infection. There
      are many disorders in which the excessive recruitment of leukocytes is
      characteristic, including chronic inflammation, atherosclerosis, arthritis,
      diabetes, asthma and reperfusion injury. Because certain cancer cells also
      express the ligand for P-selectin it is possible that this receptor is involved
      in metastasis. To study the specific role of P-selectin in these pathological
      processes, we have prepared a mouse lacking P-selectin through gene targeting.
      Leukocyte interaction with the vessel wall is defective in these animals as
      leukocytes do not roll in the mesenteric venules and their extravasation at sites
      of inflammation and vessel injury is limited. We are testing these animals in
      models of the various diseases mentioned above in order to evaluate when the
      absence of P-selectin is beneficial.

PMID- 7587630
TI  - Early metastasis of human solid tumours: expression of cell adhesion molecules.
AB  - Loss and gain of cell surface molecules determines the mobilization, emigration
      and invasiveness of epithelial cancer cells. As a first approach to gain further
      insight into these processes, we have followed two strategies: (1) to identify
      tumour cells which have disseminated early from primary carcinomas and to obtain
      information about the phenotype and prognostic significance of these cells; and
      (2) to identify molecular changes occurring in primary tumour cells at the time
      they develop their metastatic potential. Our analyses indicate that changes in
      the adhesive properties of solid tumour cells, such as down-regulation of
      desmosomal proteins (e.g. plakoglobin) and neo-expression of ICAM-1 or MUC18, are
      important determinants of the metastatic capability of individual malignant
      cells. The expression pattern of these cell adhesion molecules during tumour
      progression appears to reflect a disturbance at the level of the molecular
      elements normally responsible for controlling their expression. The outlined
      current strategies for detection, characterization and antibody therapy of cancer
      micrometastasis can be applied to the secondary prevention of metastatic disease
      in patients with minimal residual cancer.

PMID- 7587631
TI  - Creation and characterization of E-selectin- and VCAM-1-deficient mice.
AB  - A variety of adhesion molecules have been identified which mediate the
      interaction of leukocytes with endothelial cells. In order to define the role of
      individual molecules in inflammation we have produced lines of mice which are
      deficient in the synthesis of specific adhesion molecules. Null mutations were
      introduced into the genes encoding E-selectin or vascular cell adhesion molecule
      1 (VCAM-1) in embryonic stem cells and these cells were used to produce lines of
      mice carrying the mutation. E-selectin-deficient mice were viable and exhibited
      no developmental defects. The roles of E- and P-selectin in the influx of
      neutrophils were examined using these mice. The data suggest that the two
      selectins are functionally redundant in mediating neutrophil emigration in a
      model of chemically induced peritonitis. VCAM-1-deficient mice are not viable.
      Analysis of VCAM-1 gene expression in wild-type embryos and phenotypic analysis
      of VCAM-1 -/- embryos suggests that VCAM-1 is required for development of the
      extraembryonic circulatory system and the embryonic heart.

PMID- 7587632
TI  - Mechanisms of VCAM-1 and fibronectin binding to integrin alpha 4 beta 1:
      implications for integrin function and rational drug design.
AB  - Integrin alpha 4 beta 1 can mediate both cell-cell and cell-extracellular matrix
      adhesion by binding to either fibronectin or vascular cell adhesion molecule 1
      (VCAM-1). Both interactions are important for extravasation of leukocytes from
      the blood implying that rationally designed inhibitors of alpha 4 beta 1 function
      may be useful for treating a various inflammatory conditions. The mechanisms of
      ligand binding by alpha 4 beta 1 are complicated by the fact that alternative
      splicing can generate different isoforms of the receptor-binding domains in both
      fibronectin and VCAM-1. Therefore, in addition to developing alpha 4 beta 1
      antagonists, we have also been interested in identifying isoform-specific
      functions. Recombinant ligand variants have been tested in adhesion and direct
      receptor-binding assays and each molecule was found to have a different inherent
      affinity for alpha 4 beta 1 that endows them with different adhesive activities.
      This suggests that alternative splicing may regulate alpha 4 beta 1-dependent
      motility in vivo. The initial strategy that we have adopted to develop alpha 4
      beta 1 inhibitors has been to identify key amino acid residues and peptide
      sequences participating in the receptor-ligand binding event and to use this
      information to generate synthetic mimetics. Three active sites have been
      identified in fibronectin by testing truncated proteins, expressing recombinant
      fragments and screening synthetic peptides. Two of these sites employ versions of
      a novel integrin-binding motif, LDVP/IDAP. A key active site in VCAM-1 has been
      identified by similar approaches as the related sequence IDSP. Since IDSP-like
      sequences are probably used by other integrin-binding immunoglobulins,
      derivatives of these peptides may turn out to be the forerunners of a new
      generation of therapeutic agents with multiple applications.

PMID- 7587634
TI  - Treatment of inflammatory diseases with a monoclonal antibody to intercellular
      adhesion molecule 1.
AB  - A mouse monoclonal antibody to intercellular adhesion molecule 1 (ICAM-1) has
      been evaluated in multiple animal models of inflammation as well as in the
      clinic. Anti-ICAM-1 has been found to protect against allograft rejection and
      ischaemia/reperfusion injury in non-human primates and rabbits. In open-label
      phase I-II studies, anti-ICAM-1 appears to have prolonged kidney allograft
      survival when used as induction therapy in conjunction with traditional triple
      immunosuppressive therapy. Anti-ICAM-1 has shown beneficial effects in the
      treatment of rheumatoid arthritis when given for five days. Most patients
      receiving anti-ICAM-1 made antibodies to the mouse immunoglobulin.

PMID- 7587628
TI  - E-cadherin as an invasion suppressor.
AB  - The loss of epithelial differentiation in carcinomas, which is accompanied by
      increased mobility and invasiveness of the tumour cells, is often a consequence
      of reduced intercellular adhesion. Recent reports have indicated that the primary
      cause for the 'scattering' of the cells in invasive carcinomas is a disturbance
      of the integrity of intercellular junctions often involving the cell adhesion
      molecule E-cadherin. It has also been suggested that during invasion, carcinoma
      cells convert to a sort of mesenchymal stage, as do normal epithelial cells
      during development. Permanent and transient molecular mechanisms lead to the
      impairment of junction integrity of epithelial cells and thus to the progression
      of carcinomas towards a more invasive state.

PMID- 7587629
TI  - The role of CD44 splice variants in human metastatic cancer.
AB  - The large family of CD44 splice variants are likely to serve multiple functions
      in the embryo and in the adult organism. This is reflected in their complex
      patterns of expression. In molecular terms these functions are largely unknown.
      Certain splice variants (CD44v) can promote the metastatic behaviour of cancer
      cells. In human colon and breast cancer the presence of epitopes encoded by exon
      v6 on primary resected tumour material indicates poor prognosis. Metastasis
      promoting splice variants differ from those that seem not to have a role in the
      induction of metastasis by the formation of homomultimeric complexes in the
      plasma membrane of cells. This may increase their affinity to ligands such as
      hyaluronate. The affinity can be further regulated over a range from low to very
      high by cell-specific modification. The fact that CD44v epitopes are found on
      normal epithelial cells such as skin, cervical epithelium and bladder enforces
      cautious evaluation of the significance of CD44v expression in human cancer.
      Nevertheless, certain epitopes can serve as tools in early diagnosis of certain
      cancers and will facilitate the development of specific targeted therapy.

PMID- 7587636
TI  - Von Willebrand's disease and the mechanisms of platelet function.
AB  - Von Willebrand's disease, the most common congenital bleeding disorder in humans,
      is the consequence of quantitative and/or qualitative defects of von Willebrand
      factor, a protein necessary for platelet adhesion and thrombus formation at sites
      of vascular injury. The definition of the molecular basis of von Willebrand's
      disease has helped clarify the structure of von Willebrand factor as well as its
      essential role in platelet function, particularly under haemodynamic conditions
      of high shear stress. Platelets respond rapidly to alterations of endothelial
      cells by attaching firmly to the site of lesion, where exposure of subendothelial
      components may have occurred. The first layer of platelets is in contact with the
      thrombogenic surface (adhesion), whereas subsequent growth of the haemostatic
      plug depends on platelet-platelet interactions (aggregation). Both aspects of
      platelet function are influenced by von Willebrand factor binding to specific
      platelet membrane receptors as well as subendothelial structures, such as
      collagen.

PMID- 7587635
TI  - Identification of endogenous protein-associated carbohydrate ligands for E
      selectin.
AB  - A comparative analysis of carbohydrate libraries derived from cell lines binding
      E-selectin was used to identify endogenous protein-associated carbohydrate
      ligands for E-selectin. Three structures, which together constitute less than 1%
      of the total cell surface protein-associated carbohydrate, were unique to cell
      lines capable of binding E-selectin, including neutrophils and the monocytic cell
      line U937. All are tetra-antennary N-linked structures, with a sialic acid alpha
      2 --> 3 galactose beta 1 --> 4 (fucose alpha 1 --> 3) N-acetyl glucosamine beta 1
      --> 3 galactose beta 1 --> 4 (fucose alpha 1 --> 3) N-acetyl glucosamine
      lactosaminoglycan extension (sialyl-di-Lewis X [S-diLe(x)]) on the arm linked
      through the C4 residue on the mannose. While all contained the expected 3-SLe(x)
      sub-structure, these native structures have an additional fucosylated lactosamine
      unit. Direct evidence that these S-di-Lex-containing structures are high-affinity
      ligands for E-selectin came from the use of recombinant soluble E-selectin
      agarose affinity chromatography. These three carbohydrate structures bound
      specifically to the E-selectin column, while 3-SLe(x) itself does not bind under
      identical conditions.

PMID- 7587627
TI  - Defective cell-cell adhesion in the epidermis.
AB  - The disastrous effects of loss of epidermal cell adhesion are epitomized by the
      life-threatening blistering skin diseases pemphigus foliaceus and pemphigus
      vulgaris. Clinical and experimental observations show that loss of cell adhesion
      is induced by these patients' autoantibodies. Pemphigus foliaceus antigen is
      desmoglein 1 (dsg-1), a desmosomal transmembrane glycoprotein limited in
      distribution to stratified squamous epithelia. It is linked to plakogoblin, a
      desmosomal plaque protein. Molecular cloning has shown that desmogleins are
      members of the cadherin gene superfamily. The originally described cadherins
      (e.g. E-cadherin) are transmembrane, calcium-dependent, homophilic adhesion
      molecules. Pemphigus vulgaris antigen is a 130 kDa glycoprotein also linked to
      plakoglobin. Molecular cloning has shown that pemphigus vulgaris antigen is also
      a desmoglein, dsg-3. Antibodies against pemphigus vulgaris antigen subdomains
      homologous to the binding subdomains of classical cadherins cause loss of
      epidermal cell adhesion, which suggests that desmogleins mediate adhesion,
      although direct evidence for this is lacking. The extracellular domain of
      pemphigus vulgaris antigen cannot substitute in function for that of E-cadherin.
      Future studies should address the cell biological function of desmogleins.

PMID- 7587638
TI  - Leukocyte and endothelial adhesion molecules in ischaemia/reperfusion injuries.
AB  - Tissue ischaemia and/or reperfusion cause some of the injury seen in several
      clinical disorders and are responsible for considerable mortality and morbidity
      in humans. Part of the injury occurring after reperfusion of ischaemic tissue is
      the result of interactions between leukocytes adhering to vascular endothelium.
      Blocking the function of the leukocyte adhesion beta 2 integrin complex
      (CD11/CD18) leads to improved outcome following ischaemia and reperfusion.
      Functional blockade of either P-selectin or L-selectin prevents leukocyte
      rolling. Blocking leukocyte adherence at one of several levels may provide
      improved outcome in a variety of diseases associated with ischaemia and
      reperfusion.

PMID- 7587637
TI  - Leukocyte adhesion deficiency (LAD) II.
AB  - The occurrence of recurrent bacterial infections, neutrophil motility dysfunction
      and normal expression of beta 2 integrins (CD18) in two unrelated children
      suggested an as yet undescribed adhesion deficiency. The fact that both children
      exhibited the rare Bombay blood group and were Lewis negative, each involving
      carbohydrates with different fucose linkages, suggested a possible defect in the
      fucose-containing ligand for E- and P-selectin, sialyl Lewis X (SLe(x)). Using a
      monoclonal anti-SLe(x) antibody, we did not detect expression of SLe(x) on the
      neutrophils of the patients. Adhesion of neutrophils to endothelial cells
      activated with interleukin-1 beta or histamine was markedly decreased ( < 5% of
      control). The observation that the neutrophils did not bind to recombinant E
      selectin and purified P-selectin confirmed the SLe(x) deficiency as the basis for
      adhesion deficiency. Using several in vivo techniques, we were able to show that
      neutrophil rolling, the first step in their adhesion, is markedly decreased, and
      therefore neutrophil emigration through the endothelium and arrival at site of
      inflammation is significantly diminished (1-2% of normal). Low binding of fucose
      specific lectins to the patients' B lymphocytes transformed with Epstein-Barr
      virus was observed, while the binding of mannose-specific lectins was normal,
      providing further evidence for a general fucose deficiency as the primary defect.
      The existence of the patients and their deficiency emphasizes the essential role
      of the endothelial cell selectins and their ligand, SLe(x), in recruitment of
      neutrophils to sites of infection.

PMID- 7587639
TI  - The integrin alpha 4 beta 1 (VLA-4) as a therapeutic target.
AB  - Disease models in animals demonstrate that the leukocyte integrin alpha 4 beta 1
      (VLA-4) is a suitable target for therapy in a number of chronic inflammatory
      disorders. While in vivo studies have concentrated on the use of anti-alpha 4
      antibodies as proof of concept tools, repeated administration to combat human
      chronic inflammatory conditions is likely to require small antagonists of alpha 4
      beta 1. We have developed low molecular weight alpha 4 beta 1 inhibitors which
      have shown therapeutic promise in animal models of chronic inflammation.

PMID- 7587641
TI  - Somatostatin and its receptor. Introduction.

PMID- 7587640
TI  - Adhesion molecules in cutaneous inflammation.
AB  - As in other organs, leukocyte adhesion molecules and their ligands play a major
      role in cutaneous inflammatory events both by directing leukocyte trafficking and
      by their effects on antigen presentation. Skin biopsies of inflamed skin from
      patients with diseases such as as psoriasis or atopic dermatitis reveal up
      regulation of endothelial cell expression of P- and E-selectin, vascular cell
      adhesion molecule 1 and intercellular adhesion molecule 1. Studies of evolving
      lesions following UVB irradiation, Mantoux reaction or application of contact
      allergen, demonstrate that expression of these adhesion molecules parallels
      leukocyte infiltration into skin. When cutaneous inflammation is widespread (e.g.
      in erythroderma), soluble forms of these molecules are detectable in serum. In
      vitro studies predict that peptide mediators are important regulatory factors for
      endothelial adhesion molecules. Intradermal injection of the cytokines
      interleukin 1, tumour necrosis factor alpha and interferon gamma into normal
      human skin leads to induction of endothelial adhesion molecules with concomitant
      infiltration of leukocytes. In addition, neuropeptides rapidly induce P-selectin
      translocation to the cell membrane and expression of E-selectin. Adhesion
      molecules also play a crucial role as accessory molecules in the presentation of
      antigen to T lymphocytes by Langerhans' cells. Expression of selectin ligands by
      Langerhans' cells is up-regulated by various inflammatory stimuli, suggesting
      that adhesion molecules may be important in Langerhans' cell migration. The skin,
      because of its accessibility, is an ideal organ in which to study expression of
      adhesion molecules and their relationship to inflammatory events. Inflammatory
      skin diseases are common and inhibition of lymphocyte accumulation in skin is
      likely to prove of great therapeutic benefit.

PMID- 7587642
TI  - Regulation of somatostatin receptor mRNA expression.
AB  - The five somatostatin receptor mRNAs are expressed with distinct though
      overlapping patterns of distribution in the CNS and peripheral tissues. All
      receptor types are expressed in the anterior pituitary and hypothalamus and could
      therefore be modulated in states of growth hormone (GH) dysregulation. Metabolic
      perturbations such as food deprivation and diabetes mellitus lead to suppression
      of GH levels in the rat, in part due to increased somatostatin tone. In rats
      deprived of food, pituitary sstr1, 2 and 3 mRNAs were reduced by 80% compared to
      fed controls; sstr4 and sstr5 mRNAs were unchanged. Hypothalamic sstr mRNA
      expression was unaltered. In diabetic rats pituitary sstr1, 2 and 3 mRNAs were
      reduced by 50-80% with sstr1 mRNA restored in part by insulin therapy. Pituitary
      sstr4 mRNA and hypothalamic expression of these four types was unaffected. sstr5
      mRNA is reduced by 70% in the pituitary and by 30% in the hypothalamus with
      restoration of both by insulin treatment. Altered pituitary sstr expression in
      food deprivation and diabetes could result from chronic exposure to increased
      plasma somatostatin. In rat GH3 pituitary tumour cells exposed to 1 microM
      somatostatin for up to 48 h, sstr1, 3, 4 and 5 mRNA increased dramatically while
      sstr2 mRNA exhibited a biphasic response. We observed a net increase in receptor
      binding associated with increased sstr mRNA. Somatostatin receptor expression is
      regulated in a tissue- and type-specific manner, adding further complexity to the
      action of the multifaceted peptide somatostatin.

PMID- 7587643
TI  - Transient expression of somatostatin receptors in the brain during development.
AB  - The study of somatostatin receptors by means of autoradiography in tissue
      sections revealed high densities of binding sites in the immature central nervous
      system. In rat cerebral cortex, the receptors are present in the intermediate
      zone and in association with cells migrating through the cortical plate.
      Somatostatin receptors in the intermediate zone of fetuses and in the cortical
      plate of postnatal rats exhibit high and low affinities respectively for the
      somatostatin analogue MK 678. In the rat cerebellum, the external granule cell
      layer, a germinal matrix containing interneuron precursors, contains a high
      density of receptors. These receptors exhibit high affinity for MK 678 throughout
      the period of cell multiplication. In granule cell cultures from eight-day-old
      rats, MK 678, octreotide and somatostatin are able to inhibit cAMP formation
      induced by forskolin or pituitary adenylyl cyclase-activating polypeptide.
      Somatostatin reduces the intracellular Ca2+ concentration in cultured granule
      cells; this response desensitizes rapidly. These results suggest that the
      somatostatin receptors in the external granule cell layer are type 2 receptors
      (sstr2). A low density of receptors with low affinity for MK 678 was also
      detected in the external granule cell layer and in the granule cell layer of
      neonatal rats. In adult rats the cerebellum is devoid of somatostatin receptors.
      These observations indicate that somatostatin probably exerts morphogenetic
      activities through different receptor types in several structures of the central
      nervous system.

PMID- 7587644
TI  - Expression of sstr1 and sstr2 in rat hypothalamus: correlation with receptor
      binding and distribution of growth hormone regulatory peptides.
AB  - With the aim of elucidating the role of individual somatostatin receptors in the
      central control of growth hormone secretion, we have examined the distribution of
      sstr1 and sstr2 mRNAs in the hypothalamus of the adult rat by in situ
      hybridization using 35S-labelled antisense riboprobes. Both receptors were
      expressed strongly in the preoptic area, suprachiasmatic nucleus and arcuate
      nucleus. High sstr1, but low sstr2, expression was evident in the paraventricular
      and periventricular nuclei as well as in the ventral premammillary nucleus.
      Conversely, moderate to high sstr2, but low sstr1, mRNA levels were detected in
      the anterior hypothalamic nucleus, ventromedial and dorsomedial nuclei and medial
      tuberal nucleus. Within the arcuate nucleus, the distribution of cells expressing
      sstr1 and sstr2 was comparable to that of neurons which bind somatostatin-14
      selectively, one third of which have been documented to contain growth hormone
      releasing hormone. Within the periventricular nucleus, the distribution of cells
      expressing sstr1 and, to a lesser extent, sstr2 was reminiscent of that of both
      [125I]somatostatin-labelled and somatostatin-immunoreactive cells. Taken
      together, these results imply a role for both sstr1 and sstr2 receptors in the
      central regulation of growth hormone-releasing hormone and somatostatin
      secretion, and hence of growth hormone release, by somatostatin.

PMID- 7587645
TI  - Interaction of somatostatin receptors with G proteins and cellular effector
      systems.
AB  - Somatostatin induces its multiple biological actions by interacting with a family
      of receptors, referred to as sstr1-sstr5. To determine the molecular mechanisms
      of action of somatostatin, we have investigated the interaction of the different
      cloned receptors with G proteins and cellular effector systems. sstr2, sstr3 and
      sstr5 associate with pertussis toxin-sensitive G proteins and are able to mediate
      the inhibition of adenylyl cyclase activity by somatostatin. Two forms of sstr2,
      sstr2A and sstr2B, are generated by alternative splicing and differ in their C
      terminal amino acid sequence. sstr2B couples to adenylyl cyclase whereas sstr2A
      does not. To investigate the basis for the differential coupling to adenylyl
      cyclase, we truncated sstr2B to the point of amino acid sequence divergence from
      sstr2A. The truncated sstr2B mediated the inhibition of cAMP formation by
      somatostatin, indicating that the C-terminus is not needed for coupling sstr2 to
      adenylyl cyclase. It is likely that the C-terminus of sstr2A hinders coupling to
      adenylyl cyclase. sstr2A associates with Gi alpha 3 and G(o) alpha but does not
      effectively interact with Gi alpha 1, a G protein that is necessary for coupling
      somatostatin receptors to adenylyl cyclase. The differential association of the
      splice variants with Gi alpha 1 may explain their contrasting effects on adenylyl
      cyclase activity. sstr3 also couples to adenylyl cyclase. Gi alpha 1 links sstr3
      to adenylyl cyclase and mutagenesis studies have shown that the C-terminus of Gi
      alpha 1 is necessary for this coupling. The C-terminus of the Gi alpha proteins
      differ by only a few amino acid residues and only Gi alpha 1 couples sstr3 to
      adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587646
TI  - Somatostatin modulates voltage-dependent Ca2+ channels in GH3 cells via a
      specific G(o) splice variant.
AB  - In rat pituitary GH3 cells Ca2+ current through L-type channels is reduced by
      somatostatin. This modulation of channel activity by somatostatin receptors is
      mediated by a guanine nucleotide-binding regulatory protein (G protein). It is
      sensitive to pertussis toxin, indicating the involvement of a G(o)- or Gi-type G
      protein in this pathway. The identity of this G protein was determined by
      suppressing the expression of endogenous G proteins individually via intranuclear
      injection of antisense oligonucleotides. This method was applied to GH3 cells to
      screen several G protein alpha, beta and gamma subunits for their roles in the
      defined signal transduction pathway. The loss of somatostatin's modulating
      activity on the voltage-dependent Ca2+ channel after oligonucleotide injection
      revealed the involvement of G(o) alpha 2 beta 1 gamma 3 to the exclusion of other
      closely related subtypes.

PMID- 7587648
TI  - Function and regulation of somatostatin receptor subtypes.
AB  - The five known somatostatin receptors serve unique biological roles by virtue of
      their tissue-specific expression and particular biochemical properties. However,
      the function of any individual receptor in its normal physiological milieu is not
      understood. Studies to address this problem have been difficult because tissues
      and cell lines often express multiple somatostatin receptors and, in the absence
      of receptor-selective somatostatin analogues, the actions of individual receptors
      cannot be identified. Moreover, the biological and biochemical actions of
      somatostatin receptors depend on their cellular environment, so that the
      behaviour of a receptor expressed in heterologous cells does not necessarily
      mimic that of endogenous receptors. We have developed two approaches to examine
      somatostatin receptors which circumvent these problems. Using a biotinylated
      somatostatin analogue for affinity purification, we isolated somatostatin
      receptors together with associated G proteins. Subsequent analysis of the
      purified complex with G protein-specific antibodies showed that the somatostatin
      receptors in AR42J cells preferentially couple with two pertussis toxin-sensitive
      G proteins: Gi alpha 1 and Gi alpha 3. To examine individual receptor types, we
      developed receptor-specific antibodies and used them to show that both sstr1 and
      sstr2 proteins were present in the GH4C1 pituitary cell line whereas AR42J cells
      contained sstr2 but not sstr1. Immunoprecipitation of receptor-G protein
      complexes with GH4C1 cells showed that sstr1 and sstr2 are both coupled to
      pertussis toxin-sensitive G proteins, in contrast to the results observed when
      these receptors are overexpressed in some non-endocrine cells. We also showed
      that the somatostatin receptors in GH4C1 cells are subject to both homologous and
      heterologous hormonal regulation. The mechanisms involved in the regulation of
      different receptor types are now being characterized using the receptor-specific
      antibodies to isolate the individual receptor proteins. Elucidating signal
      transduction by endogenous somatostatin receptors as well as their hormonal
      regulation will be critical for understanding the functions of these receptors in
      the different physiological targets of somatostatin.

PMID- 7587647
TI  - A tyrosine phosphatase is associated with the somatostatin receptor.
AB  - Regulation of tyrosine phosphorylation is thought to be an essential step in
      signal transduction mechanisms that mediate cellular responses. In pancreatic
      tumour cells we demonstrated that somatostatin analogues inhibited cell
      proliferation and stimulated a membrane protein tyrosine phosphatase (PTP)
      activity at concentrations at which they bind to the somatostatin receptor. To
      elucidate the role of PTP in the signal transduction pathway activated by
      somatostatin receptors we first studied the interaction of PTP with the
      somatostatin receptor at the membrane. We purified somatostatin receptors by
      immunoaffinity from pancreatic membranes that strongly expressed the type 2
      somatostatin receptor sstr2. We identified the receptor as an 87 kDa protein. We
      demonstrated that a PTP activity co-purified with somatostatin receptors. The PTP
      was identified as a 66 kDa protein immunoreactive to antibodies against SHPTP1.
      These antibodies immunoprecipitated somatostatin receptors either occupied or
      unoccupied by ligand indicating that SHPTP1 is associated with somatostatin
      receptors. We then expressed sstr2A in monkey kidney COS-7 cells and mouse
      NIH/3T3 fibroblasts and demonstrated that somatostatin analogues (RC 160,
      octreotide and BIM 23014) which exhibited high affinity for sstr2 stimulated a
      PTP activity and inhibited cell proliferation in proportion to their affinities
      for sstr2. Under the same conditions these analogues have no effect on the growth
      of cells expressing sstr1. All these results suggest that a PTP related to SHPTP1
      is associated with somatostatin receptors and may be involved in the negative
      growth signal promoted by sstr2.

PMID- 7587651
TI  - Processing and intracellular targeting of prosomatostatin-derived peptides: the
      role of mammalian endoproteases.
AB  - Prosomatostatin is cleaved at dibasic and monobasic sites to produce somatostatin
      14 and somatostatin-28 respectively. The mammalian pro-protein convertases
      comprising furin, PACE4 and PC1-6 have recently been identified and are believed
      to mediate endoproteolysis of prohormone precursors such as prosomatostatin.
      Furin is membrane bound, localized to the Golgi and mediates constitutive
      processing. PC1 and PC2 are soluble and are expressed solely in endocrine and
      neuroendocrine tissues suggesting a key role in prohormone processing. We have
      investigated the endogenous and heterologous synthesis and processing of rat
      prosomatostatin in 1027B2 rat islet somatostatinoma cells and in constitutive
      (COS-7, PC-12) and regulated (AtT-20, GH3/GH4C1) secretory cells. We have
      correlated processing efficiency with: secretion through the constitutive or
      regulated pathways; endogenous expression of furin, PC1 and PC2; and expression
      or overexpression of furin, PC1 and PC2. Pulse-chase studies showed that
      prosomatostatin is rapidly and independently processed to somatostatin-14 and
      somatostatin-28. Furin is capable of monobasic processing of prosomatostatin and
      is a candidate somatostatin-28 convertase. PC1 and PC2 both effect dibasic
      processing of prosomatostatin and qualify as putative somatostatin-14
      convertases. PC1 is active in constitutive and regulated secretory cells, has a
      broader specificity and is overall more potent than PC2. Efficient processing of
      prosomatostatin begins in a Golgi or pre Golgi compartment. It requires the
      milieu of the secretory cell but not the secretory granule.

PMID- 7587650
TI  - Somatostatin analogues and multiple receptors: possible physiological roles.
AB  - The availability of transfected cell lines expressing the five cloned
      somatostatin receptors has allowed extensive families of synthetic analogues to
      be screened for their binding affinities to these receptors. Cyclic octapeptides
      in the octreotide series have high affinity for sstr2 and low affinity for sstr1
      and sstr4. Modifications to these analogues can have profound effects on their
      residual affinity for sstr3 and sstr5. Several linear peptides, incorporating the
      critical core-D-Trp-Lys-sequence of all active analogues, exhibit selectivity for
      either sstr3, sstr5 or both, but little affinity for the other three. From these
      analogues we have assembled a panel of compounds with a useful degree of
      specificity for sstr2, sstr3 and sstr5 and these have been used to evaluate
      receptor involvement in various physiological processes. Inhibition of pituitary
      growth hormone release correlates completely with sstr2 affinity and it appears
      from preliminary results that inhibition of pancreatic glucagon release is also
      sstr2 mediated. Effects on gastric acid secretion show a high degree of
      dependence on sstr2 affinity. Inhibition in vivo by somatostatin of insulin
      release, amylase release and binding to rat pancreatic acinar cells is highly
      correlated with sstr5 receptor affinity. Gastric smooth muscle cells have
      particularly high affinity for sstr3 receptor ligands. The availability of
      receptor-specific ligands is proving to be of great value in elucidating the
      physiological roles of each receptor. It is anticipated that these and future
      generations of analogues will have distinct therapeutic advantages over
      somatostatin itself and presently available cyclic octapeptides.

PMID- 7587649
TI  - Somatostatin receptors: clinical implications for endocrinology and oncology.
AB  - Somatostatin receptors are present on most hormone-secreting tumours. They are
      the pathophysiological basis for the successful control of hormonal
      hypersecretion by pituitary adenomas, metastatic islet cell tumours and
      carcinoids during treatment with the long-acting somatostatin analogue
      octreotide. There is also evidence for inhibition of tumour growth in some of
      these patients. Visualization of somatostatin receptor-positive tumours is
      possible in vivo after the administration of
      ([111In]diethylenetriaminepentaacetic acid)octreotide. Primary tumours are
      detected and often metastases that were previously unrecognized. Tumours that
      secrete growth hormone or thyroid-stimulating hormone and non-functioning
      pituitary adenomas, islet cell tumours, carcinoids, paragangliomas,
      phaeochromocytomas, medullary thyroid carcinomas and small-cell lung cancers are
      visualized in 70-100% of cases. Meningiomas, renal cell cancers, breast cancers
      and malignant lymphomas are often somatostatin receptor positive, allowing their
      localization with this scanning procedure. In some of these tumours discrepancies
      have been noted between binding studies with somatostatin-14, somatostatin-28 and
      octreotide, which suggests the presence of somatostatin receptor subtypes on some
      tumours. Most hormone-secreting tumours react in vitro to octreotide with an
      inhibition of hormone release and growth. Cultured meningioma cells react to
      octreotide with a stimulation in growth, possibly by interference with the
      autocrine inhibitory growth control by interleukin 6. This suggests that the
      presence of somatostatin receptors on human tumours does not automatically imply
      a beneficial effect of somatostatin analogue therapy.

PMID- 7587655
TI  - Characterization of somatostatin receptor subtypes.
AB  - Somatostatin regulates endocrine and exocrine secretion, possesses
      antiproliferative properties and acts as a neurotransmitter/neuromodulator in the
      central nervous system. These effects are mediated by G protein-coupled
      receptors, of which at least five types have been cloned (sstr1-5). In
      radioligand-binding studies we have compared the binding properties of sstr1-5
      with their activities as somatostatin receptors. All receptors identified so far
      bind somatostatin-14 and somatostatin-28 with high affinity. The similarities in
      receptor sequence and in the binding profiles of short synthetic somatostastin
      analogues such as octreotide, MK 678 or RC 160 for sstr1-5 indicate the existence
      of two classes of receptors sstr1/sstr4 with virtually no or very low affinity
      and sstr2/sstr3/sstr5 with intermediate to high affinity for the short
      somatostatin analogues. All five receptors mediate inhibition of adenylyl
      cyclase; this inhibition is sensitive to pertussis toxin. In vitro and in vivo
      studies suggest the importance of sstr2 and/or sstr5 in the inhibition of growth
      hormone release. The sstr2 receptor is apparently the predominant subtype
      expressed in somatostatin receptor-positive tumours. Evidence exists for the
      importance of sstr5 receptors in insulin secretion and sstr1 receptors in
      oncology. Somatostatin receptor-selective agonists and antagonists will help to
      explore new therapeutic opportunities in oncology as well as in endocrine and
      gastrointestinal disorders and those of the central nervous system.

PMID- 7587654
TI  - Regulation of somatostatin gene transcription by cAMP.
AB  - A number of hormones and growth factors stimulate target cells through receptors
      which are coupled to second messenger pathways. The second messenger cAMP, for
      example, mediates a wide variety of cellular responses to hormonal signals,
      including changes in intermediary metabolism, cellular proliferation and cellular
      motility. In mammalian cells, all of these biological responses are triggered by
      the activation of the cAMP-dependent protein kinase A, a heterotetramer
      consisting of paired catalytic and regulatory subunits. Upon hormonal
      stimulation, cAMP binds tightly to the regulatory subunits, thereby liberating
      catalytic subunits and promoting the phosphorylation of cellular substrates. In
      the liver, cAMP functions as a starvation state signal, mediating hormonal cues
      from the pancreas and adrenal gland to stimulate glucose production. cAMP
      stimulates glucose production, in part, by regulating transcription of the gene
      for phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in
      gluconeogenesis. Following hormonal stimulation, cAMP induces PEPCK gene
      expression 10-fold within 20-30 min. This induction appears to be independent of
      new protein synthesis.

PMID- 7587652
TI  - Anatomical localization and regulation of somatostatin gene expression in the
      basal ganglia and its clinical implications.
AB  - The distribution of somatostatin in both the human and rat brain suggests that it
      is involved in numerous functions, including endocrine regulation, cognition and
      memory, autonomic regulation and motor activity. We have examined the regulation
      of somatostatin mRNA in the striatum, a brain region involved in motor and
      cognitive behaviour. Somatostatin and its mRNA are expressed in this region in
      interneurons which are resistant to ischaemia, excitotoxicity and Huntington's
      disease, possibly because they express high levels of superoxide dismutase.
      Striatal somatostatin mRNA is increased by stimulation of NMDA (N-methyl-D
      aspartate) receptors. Ischaemia-induced cortical lesions also increase
      somatostatin gene expression in the striatum. In contrast, the levels of striatal
      somatostatin mRNA decrease after treatment with haloperidol, an antipsychotic
      agent that produces extrapyramidal symptoms, but not clozapine, which does not.
      Further evidence for a role for striatal somatostatin in extrapyramidal symptoms
      includes the observation that somatostatin mRNA levels decrease in the striatum
      after lesions are made in the dopaminergic pathway, a feature of Parkinson's
      disease. The largest change in somatostatin gene expression after dopaminergic
      lesions is the increase in somatostatin mRNA level sin neurons of the internal
      pallidum and lateral hypothalamus projecting to the lateral habenula. The results
      suggest that changes in brain somatostatin gene expression occur in pathological
      conditions and may be related to their symptoms.

PMID- 7587656
TI  - [Relationship between serum micronutrients and precancerous gastric lesions].
AB  - Serum micronutrient levels and their relationship to precancerous gastric lesions
      were studied in 600 subjects aged 35-64 years living in high-risk area of gastric
      cancer in Linqu County, Shandong Province. Serum micronutrient levels in local
      residents were 0.54 micrograms/ml, 0.29 micrograms/ml, 3.14 micrograms/ml, 9.62
      micrograms/ml, 30.2 micrograms/L, 924 micrograms/L, 1 016 micrograms/L, and 42.0
      micrograms/L for vitamin A, beta-carotene, vitamin C, vitamin E, selenium, zinc,
      copper and ferritin, respectively. Serum levels of beta-carotene, vitamin C and
      ferritin, and ratio of serum levels of zinc and copper correlated inversely to
      severity of pathological changes in gastric mucous membrane. With increase of
      serum level of beta-carotene or vitamin C, odds ratios (OR) of intestinal
      dysplasia and metaplasia lowered to 0.8, 0.6 and 0.9, 0.5, respectively, and with
      increase of those of both beta-carotene and vitamin C, their OR lowered further
      to 0.16, with patients of chronically atrophic gastritis as controls. It
      indicated maybe beta-carotene and vitamin C played a strong contributing role in
      protecting from development of precancerous gastric lesions.

PMID- 7587653
TI  - Molecular biology of somatostatin receptors.
AB  - The diverse physiological effects of somatostatin are mediated by a family of
      cell surface receptors that bind somatostatin selectively and with high affinity.
      The somatostatin receptors are members of the seven transmembrane segment
      receptor superfamily and molecular cloning studies have identified five types,
      designated sstr1-5. The human somatostatin receptors vary in size from 364
      (sstr5) to 418 (sstr3) amino acids with 46-61% amino acid identity between
      receptors, and 105 amino acids are invariant. The sequences of the seven putative
      alpha-helical membrane-spanning domains are more highly conserved than those of
      the extracellular N- and intracellular C-terminal domains. Two forms of sstr2
      have been identified in the mouse, sstr2A and sstr2B, which differ in size and
      sequence of the intracellular C-terminal domain. These two forms of sstr2 are
      products of a common gene and are generated by alternative splicing with sstr2A
      and sstr2B being the products of the unspliced and spliced forms, respectively,
      of sstr2 mRNA. Thus, functional diversity within the somatostatin receptor family
      may result from the expression of multiple types as well as from alternative
      splicing. The five somatostatin receptors have distinct patterns of expression in
      the central nervous system and peripheral tissues. They have also been expressed
      in vitro and shown to have different pharmacological properties. Somatostatin
      analogues selective for sstr2, sstr3 and sstr5 have been identified which will
      facilitate in vivo studies of the functions of these somatostatin receptors. Such
      studies to date suggest that sstr2 mediates inhibition of growth hormone
      secretion and sstr5 mediates inhibition of insulin secretion. The molecular
      cloning and functional characterization of the somatostatin receptor family is a
      first step in elucidating the diverse effects of somatostatin on cellular
      functions.

PMID- 7587659
TI  - [Epidemiological studies on risk for adverse pregnancy outcomes in women
      neighboring a petrochemical works].
AB  - Data of 7695 deliveries during 1985-1992 in four general hospitals neighboring a
      petrochemical works in Guangzhou were collected. Relationship between air
      pollution surrounding the plant and adverse pregnancy outcomes (APO) in women
      living there, including congenital malformation, stillbirth, low birth weight and
      preterm birth, was analyzed with air monitoring data and exposure assessment
      indices. Results showed there was difference in incidence rates of APO between
      lying-in women living in the places with various distance from the plant, and the
      incidence lowered with the distance prolonging, with a P-value of less than 0.05.
      Unconditional logistic model was used to control confounding and to estimate
      relative risks in a study of 325 cases of APO and 390 randomly sampled normal
      controls. Results indicated the distance between the places where the women
      living and the plant related to incidence of APO. It suggested air pollution
      caused by the petrochemical works may be a risk factor for APO in neighbored
      women.

PMID- 7587657
TI  - [An in vivo study on DNA-protein crosslinks induced by nickel chloride].
AB  - DNA-protein crosslinks (DPC) in the white blood cells (WBC) and lung tissues were
      detected with a new and sensitive 125I-post-labelling technique in male Sprague
      Dawley rats injected peritoneally (i.p.) with nickel chloride (NiCl2). Results
      showed DPC in the WBC and lungs of the rats increased significantly 20 hours
      after acute exposure to NiCl2. Multiple small doses (10 mg/kg i.p., twice a week
      for three weeks) of NiCl2 had similar effects as single large dose (30 mg/kg). It
      suggested DPC could be used as a biomarker to reflect genotoxicity to the WBC and
      lungs caused by nickel compound. DPC in the WBC increased more obviously than
      that in the lungs after exposure to NiCl2, and both correlated to each other. It
      showed DPC in the WBC can be used as a surrogate to indicate genotoxic lesions in
      target organs.

PMID- 7587660
TI  - [Mutagenicity and anti-mutagenicity assay of airborne suspended particles in
      Shijiazhuang city].
AB  - Samples of airborne suspended particles collected from five air monitoring sites
      in Shijiazhuang City in 1993 were analyzed with rapid synchronous mutagenicity
      and anti-mutagenicity tests. It revealed airborne suspended particles collected
      had direct and indirect mutagenicity, but no anti-mutagenicity, and there was
      seasonal difference in their mutagenicity, which showed a decreasing trend with
      an order of winter, spring, summer and autumn. Mutagenicity related positively to
      air concentrations of total suspended particles and sulfur dioxide, inversely to
      those of ozone, and did not related to those of nitrogen oxide and carbon
      monoxide.

PMID- 7587658
TI  - [Mutagenicity of tyramine extracted from salted dried fish in high-risk area of
      gastric cancer in Zhuanghe county].
AB  - Content of tyramine was determined in salted and dried small fish collected from
      high-risk area of gastric cancer in Zhuanghe County, Liaoning Province with high
      pressure liquid chromatography, and its mutagenicity after nitrosification was
      assayed. Results showed content of tyramine in the fish correlated significantly
      with its mutagenicity (r = 0.993, and P < 0.01). And, tyramine extracted from the
      fish was verified by thin layer chromatography.

PMID- 7587661
TI  - [Effects of coconut juice on the formation of hyperlipidemia and
      atherosclerosis].
AB  - Eight-week old male quails were fed with high-fat fodder supplemented by 20
      milliliters of coconut juice daily for each one for 12 weeks. Results showed
      coconut juice could increase their serum high density lipoprotein cholesterol
      levels by 46.2% and reduce their index of atherosclerosis by 41.1% and liver
      total cholesterol levels by 26.3% in quails, all with a P-value of less than
      0.01, as compared in those with high-fat fodder only. Coconut juice could inhibit
      the formation of atherosclerosis in animals obviously. Coconut juice, as a kind
      of natural and nutritious drink with an action of keeping-fit, can play certain
      roles in preventing from hyperlipidemia and atherosclerosis with a dose used in
      animal experiments.

PMID- 7587662
TI  - [Comparison of toxic effects of brucite and aluminium-treated chrysotile on
      macrophage].
AB  - Toxicity of brucite and two kinds of chrysotile (Xinkang and Sichuan chrysotile)
      treated with aluminium chloride to alveolar macrophage from guinea pigs was
      compared in vitro. Results showed changes of toxicity, indicated as generation of
      O2-., increase in membrane lipid fluidity and leakage of intracellular potassium,
      etc., caused by aluminium-treated chrysotile, were significantly lower than those
      by bructite of same dose (P < 0.05 and P < 0.01, respectively), and changes of
      other toxic indicators, such as release of lactic dehydrogenase (LDH) and acid
      phosphatase (ACP) from macrophage and its mortality, were similar to those by
      brucite. It suggests aluminium chloride can be used to antagonize pathogenic
      bioactivity of chrysotile in practice.

PMID- 7587667
TI  - [Current status and prospect of pancreas surgery in China].

PMID- 7587663
TI  - [Preliminary studies on microbe-mediated N-nitrosamide synthesis].
AB  - Chemical synthesis of N-nitrosamide and influences on it by bacteria and fungi
      isolated from human gastric juice were studied with trace analysis method to
      explore the pathway of its endogenous formation. Results showed in synthesis of N
      methyl-N-nitrosourea (MNU) with precursors of methylurea (0.42 mmol/L) and sodium
      nitrite (25 mmol/L) in a condition simulating human stomach, pH of the reaction
      system played an important role in the synthesis, the amount of synthetic
      chemical maximized at a pH of 1-3 and almost no synthesis was found at pH of 5-7.
      A study on the ability to synthesize MNU catalyzed by bacteria isolated from the
      patients with stomach cancer living in a high-risk area showed its synthesis
      could be accelerated by Pseudomonas aeruginosa at pH of 6-7 with its catalyzing
      activity existed in heat liable component of living bacteria. This is the first
      report showing microorganisms to catalyze the formation of N-nitrosamide from its
      precursors.

PMID- 7587664
TI  - [Analysis of factors causing visual disability and its preventive measures in
      China].
AB  - Analysis of sampling data from Chinese people in 1987 showed prevalence of visual
      disability was 10.08/1000. Major factors causing visual disability were
      congenital or hereditary defects, ametropia, amblyopia and corneal disease in
      children aged 0-14 years; senile cataract, trachoma and corneal disease in the
      elderly people aged 60 and over; and ametropia, amblyopia, cataract and corneal
      disease in the other people. Glaucoma and eye trauma were two major causes
      leading to severe visual disability. Suggestion of three-level prevention for
      visual disability in the country was put forward by the authors with focus on
      primary prevention, including genetic counselling and health care in pregnancy,
      preventing from eye infection and trauma, and active treatment of primary
      diseases, such as diabetes.

PMID- 7587665
TI  - [A survey on HIV and HV infection of heroin addicts in Linchang and Kunming].
AB  - Serum samples were collected from 353 heroin addicts in Linchang Prefecture and
      Kunming Area, Yunnan Province for detecting anti-HIV with ELISA and Western Blot,
      and 319 of them also for detecting various infection markers of hepatitis A, B, C
      and D with ELISA. Results showed no anti-HIV was found among them, overall
      infection prevalence rate of hepatitis A, B, C and D was 78.11%, 72.73% for males
      and 90.91% for females, and 1.57%, 63.97%, 51.85% and 5.79% positive rates for
      anti-HAV-IgM, HBV markers, anti-HCV and HDAg and/or anti-HD-IgM, respectively.
      Prevalence of mixed infection with different types of hepatitis was 40.07%, and
      35.35% for mixed HBV and HCV. Infection rate of hepatitis B and C in Kunming Area
      was significantly higher than that in Linchang Prefecture, and so did in Han
      nationality than in other minority nationalities. It suggests hepatitis viruses
      infection is caused by drug abuse, use of non-sterilizing syringes with others.

PMID- 7587666
TI  - [Early manifestation of harmful effects of methylmercury on organism].

PMID- 7587668
TI  - [Protective effects of prostacyclin on acute necrotizing pancreatitis and its
      renal damage in rats].
AB  - In a rat model with acute necrotizing pancreatitis (ANP), the administration of
      exogenous prostacyclin (PGI2) significantly increased the pancreatic and renal
      blood flow, brought the level of 6-keto-PGF1 alpha to TXB2 in renal vein blood
      back to normal, reduced the severity of pancreatic and renal histolcagic damage,
      decreased the mortality, and prolonged survival time. The study showed that
      exogenous PGI2 can increase pancreatic blood flow in rats with ANP, help to
      prevent ANP, and protect from renal damage following ANP.

PMID- 7587670
TI  - [Surgical treatment of chronic pancreatitis and evaluation of therapeutic
      efficiency].
AB  - Twenty-eight patients with chronic pancreatitis (CP) were treated surgically in
      our department from 1987 to 1994. According to imaging features of B-us, CT, ERCP
      and operative pancreatogram, CPs were classified into five imaging types: mass
      type (11 cases), mass with dilated bile duct type (8), diffusely swelling type
      (4), dilated bile and pancreatic duct type (3), dilated pancreatic duct type (2).
      The surgical procedure was determined by considering both of the imaging type and
      major symptoms. The patients with pancreatic mass were treated mainly with
      pancreatic resection, whereas the patients with dilated bile or/and pancreatic
      duct were treated with bile or/and pancreatic ductal drainage procedures.
      Sphincteroplasty, neurectomy, lithotomy and T tube drainage were combined with
      above mentioned procedures according to intraoperative findings. One patient died
      of acute cholangitis and hepatic failure, 19 patients were free of pain
      postoperatively. There was no obvious deterioration of pancreatic function. These
      data suggest that pathologic changes of CP can be shown by imaging techniques. On
      the basis of imaging features and major symptoms, choice of appropriate procedure
      or combination of various operations will improve therapeutic efficiency of CP.

PMID- 7587669
TI  - [Study of operative indication and timing for acute necrotizing pancreatitis].
AB  - 65 patients of acute necrotizing pancreatitis were reported. 36 patients
      underwent operation with a mortality of 27.8%. However the mortality in 29
      patients treated nonoperatively, the mortality was 3.4% because of their less
      critical condition. In operation group 7 out of 17 patients died (41.2%) with
      positive results in bacterial smear or culture while all 5 patients with negative
      results survived. The time from onset to admission in the survivor and the dead
      was 33 hours and 85 hours respectively. The time from onset to operation was 41
      hours in the survivor while 138.8 hours in the dead. So the prognosis related
      closely to early intensive care therapy and if indicated, surgical intervention
      timely. The indication and timing of operation were discussed.

PMID- 7587671
TI  - [The diagnosis and treatment of focalized pancreatitis: report of 16 cases].
AB  - We report 16 patients of focalized pancreatitis. All patients presented mass in
      the head of pancreas and obstructive jaundice (13 patients), characterized by
      spontaneous mass shrinkage and jaundice subsidence within two weeks after
      admission without any surgical intervention. Sonography, ERCP, exploration and
      intraoperative biopsy are of value in differentiating FP from carcinoma. Six
      patients received conservative therapy. Operations aimed to drain the commonbile
      duct and pancreatic duct (T tube drainage of commonbile duct,
      choledochojejunostomy, pancretojejunostomy) were performed in 7 patients.
      Pancretoduodenectomy were performed in 3 patients on tentative diagnosis of
      carcinoma in the head of the pancreas. Follow-up in 12 patients showed
      satisfactory results.

PMID- 7587672
TI  - [The diagnosis and treatment of insulinoma: an analysis on 20 cases].
AB  - From 1967 to 1994, a total of 20 pathologically proved benign insulinoma cases
      were treated in our hospital. Tumors were solitary in 19 cases, and multiple in
      1, with diameter ranging from 0.5 to 3.0 cm. Diagnosis was made by autopsy in one
      and by laparotomy in 19. All 18 cases except for the one dying of pancreatic
      fistula postoperatively during the same hospitalization were followed up for 1 to
      18 years without recurrence. The authors recommended calcium infusion test as the
      standard method of diagnosis, analysed the false diagnosis in one patient, and
      discussed operative experience on tumors deeply buried in the head of the
      pancreas.

PMID- 7587673
TI  - [The effect of platelet-activating factor antagonists on early bacteria
      translocation of rat after burn injury].
AB  - 30% third degree burn model of Wistar rat was used in this experiment. The
      animals were divided randomly into three groups (normal control, burn, and
      platelet-activating factor antagonist treatment). After poured E. coli which
      labelled with acridine orange into intestine, the rats were killed at 6, 12, 24,
      and 48 hrs postburn, the bacteria in mesentery lymph node (MLN), liver and
      pulmonary organisms were cultured and counted, also observed by fluorescent
      microscopy directly. The results showed that, in PAF antagonist (WEB2170)
      treatment group, the quantity of bacteria in MLN, liver and lung were decreased
      significantly (P < 0.001). The labelled bacteria in MLN, liver and lung of burn
      group were 100%, 80.0%, and 50.0% respectively compared with 40.0%, 30.0%, and
      20.0% in treatment group. It is suggested that WEB 2170 could protect the
      intestine from bacteria translocation after burn injury.

PMID- 7587674
TI  - [Biomechanics of AF new 3-d pedical screw system and treatment of 31 patients
      with unstable thoracolumbar fracture].
AB  - For anatomic reduction of the spinal frectures, the 3 dimensional multiple
      correction forces were needed. Several pedical screw systems were designed for
      reducion and fixation of the spinal fractures as the AO universal joint system
      and the RF angle screw system. Because of the contradiction of the universal
      joint and the fixed angle, a new generation of RF was designed and named AF
      (atlas fixator) system. This is a new concept of 3-D reduction, without complex
      structure as universal joint, but has truly 3-D adjustment that allowed to reduce
      the intra-canal compromise. It also provided rigid fixation to maintain the
      reduction. Comparison with CD, AO, Steffee, and RF, the AF was truly 3-D
      reduction in XTZ axis. It provided strong symmetric transmitter orthotic force to
      correct the deformity. 31 patients with unstable thoracolumbar fractures were
      treated with the new AF system. 17 had partial (15) or complete (2) neurologic
      deficits. The AF system provided accurate angle to restore the normal thoracic
      lumbar lordosis and to maintain it. All patients had a anatomic reduction by AF
      system. The spinal canal area increased over 33% by CT scan (P < 0.01). All cases
      were followed up over 8 months. No one deteriorated neurologically after AF
      fixation.

PMID- 7587675
TI  - [The prognostic significance of lymph node metastasis in surgical resection of
      esophageal cancer].
AB  - The metastatic rate and degree of lymph node (LN) were evaluated and the relation
      between prognostic significance and LN metastasis (M) was analysed through a
      retrospective study of 474 patients undergoing resections of non-irradiated
      esophageal carcinoma. In patients with LNM, the LNM rate was 44.5%. A total of
      5382 LNs were resected and examined pathologically. 690 of them were metastatic
      ones with a LNM degree of 12.8%. The 5-year survival rate of this series was
      30.6% (145/474), and was 12.8% (27/211) in patients with LNM and 44.9% (118/263)
      in those without LNM. We concluded that surgery remains the first choice of
      treatment for carcinoma of esophagus, and that meticulous LN dissection is an
      important part of surgical oncology. This is especially true when the cancer
      process is reasonably localized. However, in more advanced cases of this disease,
      surgery alone is of limited value in eradicating all cancer compromized tissue,
      and therefore the routine practice of extensive LN dissection in such cases may
      not be rewarding.

PMID- 7587678
TI  - [Anatomical study on the Riolan's anastomosis arch].
AB  - The Riolan's anastomosis arch is discussed on the basis of colon vessel
      constructions in 162 operations of the colonic interposition for esophageal
      substitution, and the materials reported in some journals. The Riolan's arch is
      not the marginal vessels of the flexura lienalis, because of its lower incidence
      (< 10%). We believe that the integrity of the arch is not responsible for the
      blood supply of the colon.

PMID- 7587676
TI  - [Quantitation of Ras p21 oncogene and DNA content of gastrointestinal smooth
      muscle tumors and prognostic significance].
AB  - Expression of ras p21 oncogene and DNA content of paraffin-embedded tissues from
      55 smooth muscle tumors of the gastrointestinal tract were analysed
      simultaneously by using immunofluorescence and flow cytometry. All of 14
      leiomyomas were found to be DNA diploid and lower-expression of ras p21. Four
      cases of DNA aneuploidy (33%) and 9 cases of ras p21 overexpression (75%) were
      found in 12 potential malignant smooth muscle tumors, while all 29 cases of
      leiomyosarcomas were aneuploidy (100%) (P < 0.005), but the rate of ras p21
      overexpression was not increased continuously (72%) (P < 0.005). 24 of 33
      aneuploid tumors (73%) were found to be ras p21 overexpression, while in 22
      diploid tumors, there were only 6 cases (27%) (P < 0.005). The outcome of the
      patients with ras p21 lower-expressed diploid tumor was excellent, compared to
      the patients with ras p21 overexpressed aneuploid tumor it was worst (P < 0.005).
      It was suggested that DNA aneuploidy and ras p21 overexpression could be regarded
      as the mark of malignancy. The overexpression of ras p21 oncogene was always
      presented in the early stage of malignant smooth muscle tumors, when the cell
      proliferation was active but the DNA content was still normal, and stable in the
      whole procss of the tumor progression. ras p21 expression and DNA content could
      supply a deficiency each other in the diagnosis and could be used as objective
      parameters in distinguishing malignancy from benign and predicting the prognosis
      of the patients with smooth muscle tumors of the gastrointestinal tract.

PMID- 7587677
TI  - [Abnormal expression and clinical significance of mutation p53 gene on human
      bladder cancer].
AB  - In order to study the relationships between the mutant p53 gene and human bladder
      cancer, the authors used in situ hybridization to detect 30 of bladder cancer and
      4 of normal bladder samples. The results showed that p53 gene positive rate of
      mRNA was 23.3% in cancer patient, and all negative in normal-bladder. The
      positive rate was significantly different in pathological grading and clinical
      stages of carcinoma (P < 0.05). It suggests that the mutant p53 gene participats
      in transformation of carcinoma and may be used as a tumor marker for
      determinating invasiveness and prognosis of bladder carcinoma.

PMID- 7587679
TI  - [Postoperative management of crisis of myasthenia gravis: analysis of 20
      patients].
AB  - From June 1983 to March 1992, 95 patients with of myasthenia gravis were treated
      with thyrmoma-thymectomy. Among them 90 patients were taken midsternotomy, and
      others standard lateral thoracotomy. All the patients had postoperative crisis of
      myathenia except one who had a cholinergic crisis. 12 patients (60%) belonged to
      type III and IV According to the Osserman's classification. The pathological
      findings showed that 17 patients had combined thyrmoma. The management for crisis
      was satisfactory with a success rate of 95%. The mortality rate was 5% (1/20) in
      early postoperative stage and 35% (7/20) in later stage, respectively. 12
      patients survived for 2.5 to 10 years. Tracheotomy, mechanical ventilation
      adjustment, control of infection of the respiratory tract, and nourishment
      supports are the key measures for successful postoperative therapy and decrease
      of mortality.

PMID- 7587682
TI  - [Direct revascularization of ischemic myocardium by laser].

PMID- 7587681
TI  - [The diagnostic value of cortical evoked potential in spinal cord injury].
AB  - From 1983-1992 CEP monitoring in spinal cord injury (SCI) was performed in 312
      cases, of them 9 were acute SCI and 303 chronic (cervical spine 57, dorsal 88,
      T11-L1 136 and lumbar 31). 179 cases were complete paraplegia and 133 incomplete
      paraplegia. CEP were negative in 175 of 179 complete paraplegia, and the correct
      diagnosis rate was 97.8%. The false positive rate was 2.2%. The changes of CEP in
      133 cases of incomplete paraplegia were prolonged latent period and/or decrease
      in amplitude. Negative CEP occurred in 5 cases, making the false negative rate to
      be 3.75%. In case of cervical SCI, the CEP of median nerve was positive when C5
      segment was intact, while radial nerve CEP was positive as C6 segment was intact.
      The ulnar nerve CEP was mostly involved in lower cervical spine injury and in
      central type of SCI because it is composed of C7, C8 and T1 segments. In dorso
      lumbar junction, there was the lower end of the spinal cord with its nerve roots,
      therefore, the CEP of T11-L1 SCI was performed by stimulating femoral, posterior
      tibial and common peroneal nerves to decrease false negative rate in incomplete
      paraplegia. Positive CEP in the femoral nerve and negative in tibial and peroneal
      nerves indicate recovery of nerve roots of lumbar plexus and no recovery of the
      spinal cord. Positive CEP in femoral, tibial and peroneal nerves represents
      recovery of the spinal cord and its roots and negative CEP in all three nerves
      indicate complete SCI, no recovery of spinal cord and its roots.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7587680
TI  - [Treatment of severe burn of knee joint with fasciocutaneous flap of the lower
      leg].
AB  - Burn of knee joint often happens on the extended side surface and hurts the
      articular capsule and cavity. Five patients with severe burn of knee joint were
      successfully treated with fasciocutaneous flap of the lower leg. After the
      operation, all the flaps survived. Three patients' articular cavity got initial
      sealing-up. Except two patients' joints merging, joint movement was normal or
      near normal, and with satisfactory appearance. The timing, key points, and
      advantages of this operation were discussed. The fasciocutaneous flap of the
      lower leg is a good selection for severe burn of knee joint.

PMID- 7587683
TI  - [Carcinoid syndrome].

PMID- 7587685
TI  - [Isolation of the lower esophagus and fundus of the stomach by specially designed
      forceps to avoid ectopic embolization during the process of coronary venous
      embolizing therapy].
AB  - To avoid ectopic embolization occasionally occuring in embolization therapy of
      coronary vein of the stomach, the authors designed forceps to temporarily isolate
      the lower esophagus and the gastric fundus. A series of 61 patients with portal
      hypertension were treated with this method from march 1990 to march 1994 with no
      ectopic embolization. The operative mortality was 1.6%. The patients were
      followed up for six months to 4.5 years, with a rebleeding rate of 6%, and an
      improved varices in 85.4% of all cases. This is a reliable method to avoid
      ectopic embolization and the individualization of embolitic dosage.

PMID- 7587684
TI  - [The posterolateral suboccipital approach to the lesions located at the anterior
      portion of the craniocervical junction].
AB  - A surgical approach to the anterior lower brainstem and upper cervical spinal
      cord consists of a fashion of unilateral suboccipital scalp flap, exposure and
      resection of the suboccipital bone and hemilamina of C1, removal of occipital
      condyle and the lateral mass of C1 (occasionally). The satisfaction of exposing
      the anterolateral portion of lower brainstem and upper cervical spinal cord can
      be obtained with minimal retraction of the nervous tissue. 13 patients, 9 with
      tumors, 2 with giant vertebral aneurysms, 2 with craniocervical malformations,
      underwent this operative procedure with no surgical mortality and morbidity which
      related to the approach.

PMID- 7587686
TI  - [Rational uses of nutritional support].

PMID- 7587688
TI  - [Use of parenteral nutritional support in patients with gastric cancer: the
      relationship of protein turn over, immunocompetence and tumor cell kinetics].
AB  - In order to elucidate the effect of preoperative parenteral nutritional support
      (PNS) on protein metabolism, host immunocompetence and tumor cell kinetics, two
      prospective trials were made in patients with gastric cancer. All the patients
      were given PNS for 7 days in addition to oral intake. The positive nitrogen
      balance and increase of protein anabolic rate was greater in PNS groups than in
      control group. There was a moderate increase in NKC after PNS. The rise in CD4+
      was significant (P < 0.05). The percentage of G0/G1 cells fell after PNS (P <
      0.01), while that of the whole proliferative phase (S + G2 + M) rose (P < 0.05).
      These changes were not noted in normal gastric mucosa. In conclusion, despite of
      stimulating tumor cell proliferation, PNS helps to promote whole body protein
      synthesis and to amelio-rate the immunocompetence of advanced gastric cancer
      patients before operation.

PMID- 7587687
TI  - [Effect of intralipid on patients with acute necrotic pancreatitis: a prospective
      clinical study].
AB  - 17 patients with acute necrotic pancreatitis were proved by CT or operation.
      These patients were randomly assigned to fat-glucose-based group (n = 9) and
      glucose-based group (n = 8). Their PN regimen consisted of nonprotein calories
      (NPC) 35-40KJ (146-167KJ)/kg/d and nitrogen 0.19-0.29g/kg/d. NPC was supplied by
      either dextrose or dextrose and intralipid. The PN duration was 2 weeks. The
      following measurements were performed: triglyceride, chorestrol, HDL, LDL, Apo-A,
      Apo-B and free fatty acids. The results showed that there was no
      hypertriglyceridemia developed after fat emulsion was administered for two weeks.
      It confirmed that fat emulsion could be rapidly oxidigzed. In our group, the
      patients with hyperglycemia were 64% at the admission time, and hyperglycemia was
      difficult to control in early period (10 days). But hyperglycemia was easly to
      control when patients received fat emulsion. There was no harmful effect on liver
      function during 2 weeks of intralipid administration. The data showed no
      difference between the two groups on conventional measurements, lysosomal enzymes
      and blood gas analysis. Intralipid infusion did not make ANP deterioration. These
      results indicated long-term intravenous intralipid in patients with ANP was safe
      and useful.

PMID- 7587690
TI  - [The effect of intralipid on the membrane fluidity of lymphocytes from human
      blood].
AB  - We observed the effect of 10% intralipid on the membrane fluidity of lymphocytes
      by means of fluorescent polarization measurement. After in vitro incubation with
      intralipid in concentration 0, 10, 20mg/ml, the lymphocytes from healthy adult
      blood showed no changes in the membrane fluidity (P > 0.05). In vivo, the
      membrane fluidity of lymphocytes did not alter significantly during and after
      infusion of 500ml 10% intralipid at a speed of 100ml per hour into healthy adult
      (P > 0.05). The level of blood triglyceride was elevated significantly during the
      infusion (P < 0.01), but decreased rapidly after the infusion. With 500ml per day
      of infusion (contral group), the surgical patients showed significant decrease in
      membrane fluidity of lymphocytes after operation (P < 0.01). But there was no
      significant difference between the study group and control group. The membrane
      fluidity might be affected by many factors. One of them is membrane lipid.
      Intralipid mainly contains triglycerides composed of polysaturated fatty acids
      and lecithin as emulsifier. The result showed that intralipid may neither alter
      the lipid composition of lymphocytes membrane nor the membrane fluidity.
      Furthermore, in case of modulation of membrane lipid composition by intralipid
      occurs, cellular self-regulation may be accomplished by fatty acid synthesis to
      keep the membrane fluidity stable.

PMID- 7587689
TI  - [Stability of amino acids and vitamins in total nutrient admixture].
AB  - We reported a formula of total nutrient admixture (TNA) used in our patients.
      During 24 hours of storage shaded from daylight at 4 degrees C and at room
      temperature (25 degrees C), the concentrations of 17 kinds of amino acids and
      vitamin A, E, B1, B2 in the TNA prepared in EVA plastic bag were not changed
      significantly. A patient who has been on this TNA for parenteral nutrition for
      more than 8.5 years is in a good nutritional status, with no clinical
      manifestations in difficiency of vitamins and proteins. 42 patients receiving
      this TNA on TPN for a period ranging from 31 to 93 days were improved
      significantly in their nutritional status.

PMID- 7587691
TI  - [Clinical observation and study of blood phosphate concentration changes in
      postoperative patients].
AB  - Blood phosphate concentration of 257 postoperative patients in the ICU was
      determined through the molybdenum-blue developing method. The results showed that
      136 cases had hypophosphatemia (blood phosphate concentration < 0.8mmol/L),
      bearing an incidence of 52.9%, which indicated that the occurrence of
      hypophosphatemia was associated with patients' age, primary disease and
      postoperative intravenous hypertonic glucose solution transfusion. Meanwhile, the
      existance of hypophosphatemia was often complicated by hypocalcemia (83.1%),
      hyponatremia (76.4%), and hypokelemia (37.5%), and furthermore, was in connection
      with organ dysfunction or failure. Of the 40 death cases among all 257, 31
      endured hypophosphatemia (77.5%). Hence, prompt diagnosis and active prevention
      and treatment of hypophosphatemia are essential to raise the cure rate of
      surgical critical patients.

PMID- 7587692
TI  - [Total parenteral nutrition support for patients with major abdominal trauma].
AB  - Thirty-two patients with major abdominal trauma were studied to evaluate the
      effects of total parenteral nutrition (TPN). There were 24 men and 8 women with
      average age of 31 years. Twenty-five cases of the group were recorded to have
      blunt trauma. Abdominal trauma index (ATI) was used to score the injury severity.
      Sixty-eight percent (22/32) of the patients had more than 15 of ATI and 25%
      (8/32) had the score over 25. TPN was given to 11 patients with complicated
      injuries of pancreas and duodenum, to 15 patients with small bowel fistula
      secondary to extended intestinal trauma, and to 6 patients with severe
      intraabdominal abscesses after injuries. The average period of TPN support was 26
      days. Nutrients were perfused with 32-42 kcal/kg/d of nonprotein energy and 0.21
      0.30g/kg/d of nitrogen. The results demonstrated that there were no changes in
      body weights. Weekly accumulative nitrogen balances increased significantly after
      the use of TPN. There were great increases of serum albumin, prealbumin,
      fibronectin and transferrin following TPN support. Blood sugar, cholesterol and
      triglyceride were in normal ranges. No TPN-related complication developed. All
      patients recovered uneventfully. It is concluded that the appropriate use of
      total parenteral nutrition can play an effective role in the treatment of severe
      abdominal traumatic patients.

PMID- 7587693
TI  - [Successful replantation in ten-digit complete amputation: a case report].
AB  - We report a case of successful replantation of ten-digit complete amputation. The
      conditions of the wounds over the ends of the ten amputated digits varied from
      severe to light and easy for replantation. The amputation included severe
      avulsion injuries over four fingers. Appropriate measures were taken during
      surgery and the replanted digits all survived. The replantation operation was
      done by a team of surgeons. Although the surgeons were physically challenged by
      the long and difficult procedures, they worked hard for the benefit of the
      patient. Physiotherapy and exercises six months after operation showed that the
      functions of both hands were largely recovered.

PMID- 7587696
TI  - [Surgical treatment of avascular necrosis of the femoral head].
AB  - 71 patients (83 hips) with avascular necrosis of the femoral head were followed
      up. The patients had bilateral necrosis (12), and unilateral (59). Their ages
      ranged from 19 to 71 years. Ficat classification showed stage I for 1 hip, stage
      II 19 hips, stage III 35 hips, and stage IV hips. According to the severity, the
      range of motion, the age, and the X-ray appearances, 6 kinds of procedures were
      used including decompression with bone grafting (32 hips), surface arthroplasty
      with cartilage (4), surface arthroplasty with fascia (4), replacement of femoral
      head (7), THA (20), and obturator neuroetomy (16). The follow-up period ranged
      from 2 years and 3 months to 10 years and 5 months. Postoperative improvement
      included pain (39.7%), range of motion (21.7%), and walking (33.7%). Among the
      procedures, decompression with bone grafting showed best results. Treatment
      revealed better results in stage I, II than in stage III, IV. We emphysize the
      early diagnosis and management, and choice of procedure should base on the
      clinical classification.

PMID- 7587694
TI  - [Foraminal and extraforaminal lumbar disc herniations].
AB  - Between August 1992 to November 1994, 7 cases of foraminal and 3 cases of
      extraforaminal lumbar disc herniation were diagnosed and operated on, which
      represented an incidence of 4.1% of all operated lumber disc herniations.
      Contrasted to the typical disc herniation, foraminal and extraforaminal disc
      herniations involved the upper nerve root mainly. The dominent symptoms and signs
      were severe anterior thigh and lower leg pain, positive femoral nerve strech
      test, impairment of knee jerk reflex and weakness of the quadriceps muscle.
      Sequestration and extrusion were the most common type of disc pathology. CT/MRI
      showed the protruded disc in and outside of the foramen clearly. It was thought
      to be ideal method for the precise diagnosis and guidance of surgery. However the
      variations of the nerve root or other diseases related to it should be
      identified. All of the 10 cases underwent surgical treatment with the approach by
      outer edge of pars interarticularis in 8. The result was encouraging with
      complete improvement in 8 cases, obvious improvement in 1 case, and partial
      improvement in another case. It was found that the approach had the advantage of
      good exposure and effect with the minimal destruction of pars interarticularis
      and facet joint which would not give rise to lumbar instability.

PMID- 7587695
TI  - [Diagnosis and misdiagnosis of fracture of the femoral head].
AB  - 164 cases of traumatic posterior dislocation of the hip, of which 26 were
      associated with fractures of the femoral head, about 15.9% incidence, were
      treated during the year from March 1982 to March 1993. According to the pipkin
      classification of fractures of the femoral head, 10 cases were type 1, 6 tupe 2,
      2 type 3, and 8 type 4. Of the 26 cases, 24 received emergent radiography, with
      22 diagnosed and 2 misdiagnosed. The other 2 cases were found prompt auto
      reduction of dislocation of the femoral head, without emergent radiography. The 4
      misdiagnosed cases, because of continued pain or redislocation, came back later
      for radiography and then were correctly diagnosed. Besides the routine
      anteroposterior radiograph of the hip, pelvic oblique radiography angled 45
      degrees or 60 degrees, and frog-leg anteroposterior hip radiography were needed.
      The CT-directed pelvic oblique radiograph was found to be the most accurate
      determinant of the extent of fracture displacement and the presence of
      intrasarticular loose fragments. Among the 19 cases operated on, 16 showed
      excellent-good rate (50%), and among the 7 non-operated cases, of 6 showed
      excellent-good rate (33%). After follow up.

PMID- 7587697
TI  - [Mesenteric vein thrombosis after devasculation for portal hypertension].
AB  - Six patients with mesenteric vein thrombosis (MVT) after devasculation for portal
      hypertension were treated by intestinal resection. Two patients had recurrence of
      thrombosis after the initial operations. Among 6 patients 2 survived and 4
      (66.7%) died. MVT is an underappreciated, patentially lethal complication after
      revasculation. Three pathogenic factors after the operation may lead to thrombus
      formation of the portal vein, portal congestion, hypercoaguble state, and
      extensive ligation of portal branches. The complication commonly occurs in the
      recent period after devasculation. It is a characteristic manifestation of MVT
      that abdominal pain is out of proportion to physical findings. The most effective
      method is resection of infarcted bowel with sufficient length of normal bowel and
      its mesentery. In order to avoid a recurrence of thrombosis, postoperative
      anticoagulation treatment should be given.

PMID- 7587698
TI  - [Surgical treatment of penoscrotal transposition associated hypospadias].
AB  - Thirty-four patients with penoscrotal transposition associated with hypospadias
      were surgically treated from 1978 to 1992. Penoscrotal hypospadias was noted in
      23, and perineal hypospadias in 11. Incomplete penoscrotal transposition was scen
      in 24 patients, and complete penoscrotal transposition in 10. 32 patients out of
      34 obtained satisfactory results after the correction of penoscrotal
      transposition. Complication occurred in 5 patients (urethral fisula 3 and orifice
      structure 2). The operative procedures of penoscrotal transposition were
      discussed.

PMID- 7587699
TI  - [The reconstruction of facial burn and deformity from burn scar].
AB  - Thirty-seven patients with facial full-deep burn and burn scar contructure were
      treated in our department. The operation included transplantation, of whole piece
      of full thickness skin (3 patients), transplantation of whole piece of full
      thickness skin with subdermal vascular rete a (1), transplantation of improved
      whole piece of full thickness skin (26), and separated transplantation of large
      piece of partial thickness skin (7). Follow-up from 3 to 15 years showed that the
      facial skin of whole piece of full thickness skin was soft, smooth, and had
      natural facial expression. The facial skin of separated transplantation had
      slight scar and pigmentation. The improved whole piece of full thickness skin was
      recommendable for avoiding the secondary ectropion of eyelid and lip.

PMID- 7587700
TI  - [The preventive recurrent results of postoperative intravesical instillation
      therapy in bladder cancer].
AB  - From Jan. 1988 to Nov. 1992, 441 patients with bladder carcinoma were
      hospitalized in our department. 385 of them were treated by transurethral
      resection of bladder tumor (TURBT) or partial cystectomy. After surgical
      management, the instillation therapy with BCG, TTP or MMC, etc was used to
      prevent tumor recurrence in 321 patients. Follow-up for 1-7 years showed that the
      mortality rate was 6.9% (22/318), and the tumor recurrence rate in BCG, TTP, MMC
      and control groups was 18.1%, 31.2%, 29.6% and 46.1% respectively. The factors
      influencing the tumor recurrence and the prophylactic effect of BCG instillation
      immunotherapy were discussed.

PMID- 7587702
TI  - [Compositive treatment of acute deep vein thrombosis of lower extremity].
AB  - Fourteen patients with acute deep vein thrombosis of lower extremity (DVT) were
      treated with composite methods including thrombectomy (iliofemoral venous
      thrombectomy and ascending venous thrombectomy), thrombolytic and anticoagulant
      therapy. Follow-up for 2-27 months (average 11.5 months) showed excellent and
      good results in 78.6%, and the morbidity of post-thrombotic syndrome only 21.4%.
      The remarkable results were due to opening of occlusive vein of the lower
      extremities by thrombectomy, which could make thrombolytics effective and reduce
      the dose of thrombolytics to prevent bleeding complication. Ascending venous
      thrombectomy could not only remove the venous thrombi of the lower extremities
      but also protect the deep venous valves and reduce the morbidity of
      postthrombotic syndrome. Additionally, to reach a satisfied therapy, lesion in
      iliac vein, such as anatomical compression, stenosis, occlusion, diaphragm and so
      on, shall be managed as well. Otherwise, DVT shall be recurrent.

PMID- 7587703
TI  - [Osteoclastic resorption of Haversian system of femoral neck cortex in aged
      women].
AB  - Osteoclastic resorption was studied with scanning electron microscope on cross
      sections of cortical bone of femoral neck collected from 7 aged women with an
      average age of 72.4 years, who underwent endoprosthetic replacement for
      intracapsular hip fracture. The cortical bone sections revealed enlargement of
      the Haversian canals. On the inner linings of the enlarged canals there were many
      oval-shaped resorption lacunae, reflecting osteoclastic resorption of the
      Haversian systems. The osteoclastic resorption with subsequent enlargement of the
      Haversian canals into round or oval cavities took place first over the inner
      portions of the cortical sections, thereby rendering these areas porotic
      (cancellization). These processes of the Haversian system and canals then
      gradually emerged over the central and eventually over the outer areas of the
      cortical bone, and the entire cortical bone became porotic. In the meanwhile, the
      inner porotic portion of the cortex turned into trabeculae (trabecularization)
      and became gradually resorbed, resulting in thinning of the medial cortex.
      Cortical cancellization, trabecularization and thinning so compromised the
      material strength of the femoral neck that fracture would ensue even with trivial
      injury.

PMID- 7587701
TI  - [Comparitive study of three images examination in preoperative localization of
      parathyroid adenoma].
AB  - The ability to localize parathyroid adenoma with B ultrasound, CT scan and thal
      lium-technetium scanning (TTS) was eraluated in 41 randomly selected patients
      with parathyroid adenoma proved pathologically from May, 1985 to May, 1993. The
      results indicated that the sensitivity was 92.86%, 73.91% and 33.3%; the
      specificity, 95.65%, 94.2% and 100%; and the accuracy, 95%, 89.1%, 83.3% in above
      three images examinations. Therefore, the predictable positive rates were 86.6%,
      80.95 and 100%; the predictable nagative rates were 97.78%, 91.55%, 0%. There was
      no significant difference between B ultrasound and CT scan (P > 0.05) in the
      detection of the location of adenomas. We suggest that B ultrasound could be the
      first choice in the detection of the location of parathyroid adenoma before
      surgery, and the CT scan be applied for the unascertained patents who had B
      ultrasound exam, or surgical exploration, and those with suspected mediastinal
      adenoma.

PMID- 7587704
TI  - A model for evaluation of in situ hybridization spot-count distributions in
      tissue sections.
AB  - The interpretation of in situ hybridization (ISH) spot-count distributions,
      obtained from evaluation of ISH signals in tissue sections, is complicated by the
      unknown impact of nuclear truncation and of the localization of ISH spots within
      the nuclei. In this study, a mathematical model was developed to investigate the
      effects of nuclear truncation and of the distribution of ISH spots within the
      nucleus on the ISH spot-count distribution in tissue sections. In this model, it
      was assumed that nuclei are spherical and of constant diameter and that ISH spots
      have negligible size and are distributed randomly within the nucleus ("volume
      model") or along the nuclear membrane ("surface model"). A minimal nuclear
      profile diameter was introduced in order to study the effect of rejecting small
      nuclear fragments for spot-count evaluation. Given the section thickness, the
      nuclear size, the minimal nuclear profile diameter, and the true number of ISH
      spots per nucleus and their spatial distribution within the nucleus, the model
      predicts the proportion of nuclei observable in the section with a specific
      number of ISH spots. A program that performs the model calculations was developed
      for PC and is available upon request. For section thickness greater than 50% of
      the nuclear diameter, the main effect of increasing section thickness on spot
      count distributions was the increase of the proportion of nuclei with the true
      chromosome copy number of spots. For lower section thickness, the total
      distribution shifted towards lower spot frequencies. The influence of the minimal
      profile diameter was most notable for values close to the nuclear diameter. The
      effect of the localization of ISH spots within the nucleus was shown to be
      prominent, especially for sections with thickness smaller than the nuclear
      diameter. Good correspondence between model-predicted distributions and measured
      distributions was obtained using the volume model and taking into account only
      large nuclear profiles.

PMID- 7587705
TI  - Methods for cell proliferation analysis by fluorescent image cytometry.
AB  - Methods were developed for multimodal microscopic image analysis in order to
      identify and analyze one cell type under various microscopic conditions. Our
      purpose was to quantify both total DNA content using propidium iodide (PI) stain
      and S-phase fraction using the bromodeoxyuridine (BrdUrd) incorporation technique
      in cell population subsets. The model chosen was plasma cells in bone marrow
      triply labelled with fluorescein isothiocyanate (FITC) for intracytoplasmic
      immunoglobulins, with amino-methylcoumarin-acetate (AMCA) for BrdUrd, and with PI
      for DNA. Image analysis included three phases. First, plasma cells were
      recognized on FITC images, and the centroid positions were stored. Second, plasma
      cell nuclei were geodesically reconstructed from these stored positions using PI
      images in which DNA content was measured, and the nuclear mask outlines were
      stored. Third, BrdUrd incorporation level of plasma cells was measured on AMCA
      images inside PI nuclei masks and stored. Image DNA vs. BrdUrd scatterplots were
      obtained for cells selected according to the expression of intracytoplasmic
      immunoglobulin. Thus, both ploidy and proliferation could be independently
      evaluated on a subset of the cellular population.

PMID- 7587708
TI  - Binding diversity of antibodies against external and internal epitopes of the
      multidrug resistance gene product P-glycoprotein.
AB  - P-glycoprotein (Pgp) is a trans-membraneous protein that is associated with
      multidrug resistance (MDR) in human cancer, including hepatocellular carcinomas
      and leukemias. There is no consensus regarding methods of choice for analysis of
      Pgp expression, and development of reliable analytical methods is now essential.
      We have studied the the Pgp expression in human hepatoma and leukemia cell lines
      using flow cytometry. The aim of the study was to compare binding properties of
      anti-Pgp antibodies reacting with surface (MRK16, UIC2) and cytoplasmic (C219,
      JSB-1) epitopes to assess which antibody performed best with respect to
      fluorescence discrimination. By histogram subtraction the fractions of resistant
      human hepatoma cells positive for Pgp were 99% (MRK16), 97% (UIC2), 77% (JSB-1),
      and 51% (C219), demonstrating variations in antibody reactivity. The resolution
      in detecting decreasing levels of Pgp in hepatoma cells was superior for the
      externally binding antibodies, showing that there is a correlation between
      antibody reactivity and fluorescence discrimination. Similar results were
      obtained for parental and resistant KG1a human leukemia cell lines. The Pgp
      epitopes remained reactive to the anti-Pgp MAbs after methanol fixation and
      cryopreservation. By dual parameter flow cytometry it was shown that Pgp
      expression in viable cells may be assessed together with uptake of epirubicin,
      which was low in cells expressing high levels of Pgp and vice versa. In
      conclusion, all tested antibodies proved useful for flow cytometric detection of
      high levels of Pgp, but the externally binding ones were superior in detection of
      low and variable levels of Pgp.

PMID- 7587707
TI  - Dyes providing increased sensitivity in flow-cytometric dye-efflux assays for
      multidrug resistance.
AB  - In an effort to improve detection of P-glycoprotein-mediated multidrug resistance
      (mdr), several dyes were compared to rhodamine 123 (R123) in efflux assays. Two
      dyes (SY-38 and SY-3150) were found that provided better sensitivity. These dyes
      were effluxed by a cell line known to be mdr-positive (P388/R84) but not by an
      mdr-negative cell line (P388). Efflux was blocked by both verapamil and
      cyclosporine A. Efflux from KG1a cells was less than from P388/R84, just as has
      been seen with R123 and daunomycin. In further experiments, a model system was
      used to demonstrate two-color immunofluorescence plus efflux measurements. This
      was done using a sequential staining method. A procedure was devised that, at
      least for this model system, allowed single-step staining with both dye and
      antibody. The sensitivity of the efflux measurement was slightly compromised by
      using this one-step staining method.

PMID- 7587709
TI  - Scatchard analysis of fluorescent concanavalin A binding to lymphocytes.
AB  - Standard Scatchard analysis of ligand binding to cell receptors requires the use
      of isotopes and is imprecise at low ligand concentrations. To evaluate the
      feasibility of Scatchard analysis via fluorescence flow cytometry, the binding of
      fluorescein isothiocyanate-derivatized concanavalin A (FITC-ConA) to murine
      lymphocytes at 4 degrees C was compared to 125I-ConA binding. A FACS IV flow
      cytometer (Becton-Dickinson, Mountain View, CA) was used for analysis of cells
      after fluorescent ligand binding. A simple spectrophotometric technique was used
      to calibrate the relation between cytometer-determined fluorescence and ligand
      binding per cell. As FITC-ConA binding showed a quasi-Gaussian distribution, the
      mean number of molecules bound per cell was easily calculated. Scatchard analysis
      of FITC-ConA binding yielded results (1.9 x 10(6) receptors/cell, K = 3.6 x 10(
      15)) similar to those obtained with 125I-ConA (1.4 x 10(6) receptors/cell, K =
      5.2 x 10(-15)). Cytometric Scatchard plots showed less scatter and seemed more
      precise, suggesting superiority to radioactive ligand measurements, particularly
      at low ligand concentrations.

PMID- 7587706
TI  - Classification and regression trees for bone marrow immunophenotyping.
AB  - Methods are needed to assist with automating three-color flow cytometric
      immunophenotyping of bone marrow from leukemia patients. Described is a method in
      which a normal bone marrow data set is used as a template against which to
      compare leukemic bone marrow data sets. This template is obtained using
      techniques of cluster analysis and cluster editing. Leukemic cells often
      inappropriately express antigens and appear in a different part of the
      multivariate data space than normal cells. To recognize the cells exhibiting
      inappropriate antigen expression, an artificial cluster of "cells" is added to
      the normal template. The "cells" in this cluster fill the space not occupied by
      normal cells. Classification and regression tree (CART) analysis is used to train
      a classifier that can then be used to isolate the major cell types and the
      inappropriate expression cells in a leukemic bone marrow specimen.

PMID- 7587711
TI  - Adaptation of the TdT assay for semi-quantitative flow cytometric detection of
      DNA strand breaks.
AB  - The enzyme Terminal Deoxynucleotidyl Transferase (TdT) is a DNA polymerase which
      can be used to label DNA strand breaks by the incorporation of a labelled
      nucleotide followed by a fluorescent detection step. The amount of label
      incorporated can then be assessed by flow cytometry. The mechanism of action of
      TdT, however, will allow the addition of varying numbers of nucleotides to the
      free 3' termini produced by DNA strand breaks. The substitution of Digoxigenin
      (DIG) labelled dideoxy-nucleotides for labelled deoxy-nucleotides in the TdT
      assay will limit the addition of label to a DNA break to a single nucleotide,
      thus ensuring a direct relationship between an increase in DNA strand breaks and
      an increase in fluorescence. We have used this adaptation of the TdT Assay to
      evaluate DNA damage incurred in lymphocytes, from patients with Chronic
      Lymphocytic Leukaemia (CLL), on exposure to UV irradiation and apoptosis-inducing
      drugs, fludarabine and 2-Chloro-2'-deoxyadenosine (2-CdA). This technique may
      give a good indication of the susceptibility of CLL patients to apoptosis
      inducing drugs, and hence an indication of the likely response to these
      therapies.

PMID- 7587710
TI  - Further characterisation of the in situ terminal deoxynucleotidyl transferase
      (TdT) assay for the flow cytometric analysis of apoptosis in drug resistant and
      drug sensitive leukaemic cells.
AB  - Apoptosis, originally defined by specific morphological changes, is characterised
      biochemically by non-random cleavage of DNA. Depending on cell type, this DNA
      cleavage proceeds from 300 and 50kbp fragments prior to, concomitantly with, or
      in the absence of 180bp integer fragmentation. Incorporation into fragmented DNA
      of biotin-labelled nucleotides by terminal deoxynucleotidyl transferase (TdT) has
      recently become a standard flow cytometric assay for the identification and
      quantitation of apoptosis. Nucleotide incorporation is visualized using avidin
      tagged fluorescein isothiocyanate (FITC) (Gorczyca et al.: Cancer Res 53:1945
      1951, 1993; Jonker et al.: Cytometry (Suppl 13):Abstr 99A, 1993). Here, we
      characterise this assay further in three different haemopoietic cell lines. Drug
      induced DNA damage is not identified by the TdT assay unless it is coupled to the
      apoptotic response. This was demonstrated using cells in which activation of the
      oncogenic Abelson-encoded protein tyrosine kinase suppressed drug-induced
      apoptosis, but did not inhibit drug-induced DNA damage (by melphalan,
      hydroxyurea, or etoposide). Furthermore, the TdT assay identifies DNA fragments
      formed during apoptosis induced by etoposide and N-methylformamide in HL60 and
      MOLT-4 cells, including those high molecular weight DNA fragments formed in MOLT
      4 cells which were not further cleaved to 180-200bp integer fragments. Our
      results support the use of flow cytometry and the TdT assay to reliably measure
      apoptotic cells in heterogeneous cell samples.

PMID- 7587712
TI  - Estimation of fetal hemoglobin levels in individual red cells via fluorescence
      image cytometry.
AB  - A method for estimating fetal hemoglobin (Hb F) levels in individual red blood
      cells was developed. Cell smears were prepared using a slide maker to ensure
      uniform thickness and were then stained with immunofluorescence. An antifading
      gel was applied to preserve a stable fluorescence. The total fluorescence
      intensities from the same number of red cells in different slide specimens
      correlated with their hemolysate Hb F levels, which were determined via column
      chromatography (R = 0.95). Hb F level in individual cells was estimated from
      fluorescence intensity and cell area, which were determined via image analysis
      techniques and the hemolysate Hb F level. Blood from a normal subject, a subject
      with hereditary persistence of fetal hemoglobin, and from sickle cell patients
      with varying Hb F levels was analyzed. Our analyses showed a wide distribution of
      Hb F among cells for the normal subject and a gaussian distribution with a peak
      at the hemolysate Hb F level for the subject with hereditary persistence of fetal
      hemoglobin. The Hb F distributions were unique to the patients with sickle cell
      disease. Because Hb F level in individual sickle cells is crucial to the
      inhibition of cell sickling, the unique hb F distribution may be important in
      determining the clinical course of this disease.

PMID- 7587713
TI  - Optimal bone marrow sample for cell kinetic studies.

PMID- 7587716
TI  - Standardization of a flow cytometric method for measurement of low-density
      lipoprotein receptor activity on blood mononuclear cells.
AB  - Flow cytometric methods for measurement of low-density lipoprotein (LDL) receptor
      activity on peripheral blood mononuclear cells (PBMC) may be used to identify
      patients with familial hypercholesterolemia (FH). However, cellular LDL receptor
      activities measured in FH heterozygotes may overlap with those of healthy
      subjects. Analytical variation is probably responsible for some of this overlap.
      We have examined several technical details that may affect analytical variation.
      In each analysis, we included one standard and two control cell preparations.
      These were cells isolated from three donors and stored in aliquots at -135
      degrees C. Use of standard cells reduced between-series analytical variation of
      the controls by approximately 50%. Preincubation-conditions used to induce the
      maximum number of receptors, the concentration of fluorochrome 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine-perchlorate (DiI)-LDL, labelling time, and
      conditions during storage of labelled cells before flow cytometry were also
      examined in order to reduce analytical variation. Having standardized the assay,
      we found among 20 healthy subjects a median receptor activity of 100% vs. 51%
      among 26 patients who fulfilled clinical criteria for FH. However, four of the
      patients showed distinctly normal receptor activities, which may suggest either
      the presence of some other biochemical defect or that in vivo dysfunctional
      receptors may be measured as normal in some patients with our assay.

PMID- 7587714
TI  - Occurrence and a possible mechanism of penetration of natural killer cells into
      K562 target cells during the cytotoxic interaction.
AB  - The cytotoxic interaction between cloned human Natural Killer (NK) cells and K562
      target cells was studied using confocal laser scanning microscopy (CLSM) and
      conventional fluorescence microscopy. We observed, using fixed as well as living
      cells, the occurrence of (pseudo) emperipolesis during the interaction. About 30%
      of conjugated NK cells penetrated, partly or completely, into the target cells
      (in-conjugation). Virtually all in-conjugated target cells exhibited polymerized
      actin. Killer cells of in-conjugates were frequently seen approaching the target
      cell nucleus or aligning along it. If the cytotoxic process was inhibited by the
      absence of calcium neither actin polymerization nor in-conjugation were observed.
      A kinetic study showed that in-conjugation starts somewhat later than actin
      polymerization but still within a few minutes after addition of calcium to
      conjugates previously formed in the absence of calcium. The presence of
      cytochalasin D (an inhibitor of actin polymerization) completely inhibited in
      conjugation and partly reduced the cytotoxic activity. Zinc ions (endonuclease
      inhibition) inhibited in-conjugation and decreased the total number of target
      cells with polymerized actin in a concentration dependent manner. Cytotoxic
      activity was also reduced but not as efficiently as in-conjugation. Our study
      demonstrates that in-conjugation represents a significant fraction of the
      cytotoxic interaction. The results indicate that it may be a consequence of an
      actin polymerization and endonuclease activity dependent part of a cytotoxic
      mechanism.

PMID- 7587715
TI  - Changes in intracellular calcium concentration and pH of target cells during the
      cytotoxic process: a quantitative study at the single cell level.
AB  - This study reports on the changes in intracellular calcium concentration
      ([Ca2+]in) and intracellular pH ([pH]in) that occur in K562 target cells during
      interaction with human Natural Killer (NK) cells. The data were obtained using a
      quantitative fluorescence microscope and fluorescent ratio probes specific for
      [Ca2+]in (Fura-2-AM) and [pH]in (BCECF-AM). Results demonstrate that two types of
      target cell response to the attack by an NK cell can be distinguished. The target
      cell either dies immediately, due to the complete breakdown of the membrane
      impermeability, or the initial membrane damage (i.e., increased membrane
      permeability) is repaired and the cell "escapes" immediate death. During both
      responses an increase of [Ca2+]in takes place in the target cells. In the cells
      that die immediately, however, [Ca2+]in reaches higher levels (approximately
      1,400 nM) than in the cells that restore the initial damage (approximately 700
      nM). Changes in target cell [pH]in are also detected during both responses. The
      direction of the change (acidification or alkalinization) as well as the level of
      the change depend on extracellular pH ([pH]ex). Also, [pH]in remains changed
      during the time the cells were followed (10 min). The programming time (i.e., the
      time from the initiation of the cytotoxic process to the time that a change in
      the physiological parameter was detected) of the killing process that leads to an
      immediate target cell death appears to be shortest at [pH]ex 7.3-7.6
      (approximately 3 min).

PMID- 7587717
TI  - High affinity binding of 7-aminoactinomycin D and 4',6-diamidino-2-phenylindole
      to human neutrophilic granulocytes and lymphocytes.
AB  - The binding behavior of the DNA binding dyes 7-aminoactinomycin D (7-AAMD) and
      4',6-diamidino-2-phenylindole (DAPI) to human neutrophilic granulocytes and
      lymphocytes was studied by image cytofluorometry. Peripheral blood leukocytes
      were prefixed in paraformaldehyde (PFA) and attached to cover glasses. Different
      fixation, permeabilization, and acid extraction method were applied before the
      cells were stained to equilibrium using varying concentrations of 7-AAMD or DAPI.
      The apparent association constant and number of high affinity dye binding sites
      were estimated for the different cell types, dyes, and treatments. Acid-extracted
      cells, supposedly containing nucleosome-free DNA, were chosen to represent
      maximal dye binding. Only about 10% of the 7-AAMD binding sites remained in the
      unextracted PFA-fixed cells, and the apparent dye affinity was also reduced. We
      found no major difference in high affinity binding between the cell types, but
      granulocytes showed more fluorescence from less specifically bound 7-AAMD
      compared to lymphocytes. DAPI had a much higher affinity than 7-AAMD, independent
      of the preparation method. It showed a cooperative binding behavior with an
      apparent saturation of the high affinity binding sites at a dye concentration of
      about 50 nM. We conclude that both dyes may be useful as probes for chromatin
      structure in intact cells and that our new technique may contribute to such
      studies since it allows determination of dye affinities and numbers of high
      affinity binding sites in situ.

PMID- 7587718
TI  - Flow cytometric assessment of the cellular pharmacokinetics of fluorescent drugs.
AB  - Development of multidrug resistance (MDR) in cancer cells decrease net
      doxorubicin uptake as a result of either increased efflux, or decreased
      intracellular sequestration, or decreased membrane permeability. Kinetic
      parameters of drug uptake can distinguish among these forms of altered transport.
      Cellular uptake of fluorescent drugs was monitored by a flow cytometric assay
      using a rapid-injection system and analyzed with a three-compartment model in
      which rapid diffusion from extracellular fluid into the cell was followed by
      uptake into a nonexchangeable pool. In agreement with our recent studies of 14C
      doxorubicin distribution (Dordal et al.: J Pharmacol Exp Ther 271:1286-1290,
      1994), sequestration of doxorubicin was decreased 2.7-fold in P-glycoprotein
      expressing SU-4R lymphoma cells compared to drug-sensitive SU-4 cells (14.0 +/-
      4.8 vs. 5.0 +/- 0.9 nl s-1) without a change in membrane permeability or evidence
      of active efflux. In contrast, sequestration of the highly fluorescent dye
      rhodamine 123 was decreased 20-fold (17.1 +/- 8.3 vs. 0.9 +/- 0.8 nl s-1).
      Resistant cells were significantly less permeable to rhodamine than sensitive
      cells (3.8 +/- 1.2 vs. 10.2 +/- 2.6 x 10(5) cm2 s-1), and rhodamine efflux was
      increased by 24%. Thus, SU-4R cells exhibit multiple alterations that cause
      decreased intracellular drug concentrations, of which decreased sequestration is
      quantitatively the most significant.

PMID- 7587719
TI  - Influence of S9788, a new modulator of multidrug resistance, on the cellular
      accumulation and subcellular distribution of daunorubicin in P-glycoprotein
      expressing MCF7 human breast adenocarcinoma cells.
AB  - A triazinoaminopiperidine derivative synthesized as a modulator of multidrug
      resistance, S9788, was investigated in the human breast adenocarcinoma MCF7DXR
      cell line expressing P-glycoprotein. In addition to being less sensitive to
      daunorubicin, the resistant cell line showed dramatic alterations in the
      subcellular distribution of daunorubicin, as observed via fluorescence microscopy
      and quantified via tritiated daunorubicin nuclear distribution analysis. Compared
      to verapamil and cyclosporin A at 2 and 5 mumol/liter, S9788 proved to be more
      potent in restoring the cellular accumulation and the subcellular distribution of
      daunorubicin in the resistant cells. Significant activity of S9788 was observed
      at 2 mumol/liter, which is clinically achievable, and S9788 restored the nuclear
      distribution of the drug to the level observed in the parental sensitive cell
      line. Consequently, the restoration of the cytotoxicity of daunorubicin by S9788
      was nearly complete (> 90%) at 2 mumol/liter, wheras cyclosporin A reached this
      level of activity at 5 mumol/liter, and verapamil was always less active at both
      concentrations. These results suggest that the modulation of multidrug resistance
      by S9788 is not only related to the enhancement of the cellular accumulation but
      also especially by the restoration of the subcellular distribution of the drugs
      to their nuclear sites of action.

PMID- 7587720
TI  - Flow cytometric study of differentiating cultures of Bacillus subtilis.
AB  - We report on 1) the development of a flow cytometry-based technique for detecting
      beta-galactosidase in differentiating cultures of Bacillus subtilis and 2) the
      application of this technique in the study of early developmental gene
      expression. The problems associated with generating detectable signals (despite
      the small size of B. subtilis cells) have been overcome using the fluorogenic
      substrate 5-octanolyaminofluorescein di-beta-D-galactopyranoside (C8-FDG).
      Additionally, to control for background fluorescence during the staining process,
      we included a control population in the C8-FDG staining mixture that consists of
      cells devoid of the lacZ gene prestained with another dye, PKH26. The distinct
      emission spectra of C8-fluorescein and PKH26 allow nonspecific C8-FDG staining in
      this control population to be monitored using two-color analysis. This technique
      has been applied in the study of developmental gene expression in sporulating
      cultures of B. subtilis, and it has been found that such cultures are
      heterogeneous, comprising two cell populations. One population is induced for
      expression of early sporulation genes, which is determined using lacZ fusions,
      whereas the other remains uninduced. These results have allowed us to understand
      better the patterns of gene expression exhibited by wild-type and mutant cultures
      early during the development process of spore formation.

PMID- 7587721
TI  - Flow cytometric determination of aminopeptidase activities in viable cells using
      fluorogenic rhodamine 110 substrates.
AB  - Aminopeptidases (AP) are ubiquitously occurring, nonspecific exopeptidases
      involved in protein degradation. They cleave the N-terminal amino acid of
      peptides and occur in practically all mammalian cells and tissues. Physiological
      and pathological processes such as metastasis of tumors and inflammation have
      been thought to involve changes in AP activities. Determination of AP (EC
      3.4.11.X) activity in viable cells by flow cytometry was the subject of this
      study because of its general biological and clinical interest. Different bis
      substituted rhodamine 110 (R110) peptide derivatives were synthesised and used as
      AP- and exopeptidase (EC 3.4.13.X-EC 3.4.14.X) substrates for flow cytometric
      measurements. Intracellular AP activities in viable lympho-, mono-, granulo-, and
      thrombocytes were detected by fluorescence increase from R110 following
      intracellular substrate cleavage. Eukaryotic-AP do not cleave D-amino acids and
      hence NH2(D-Leu)2R110 substrate served as negative control. Specific substrate
      cleavage by AP is shown by complete inhibition of flFLuorescence generation
      following preincubation of cells with leucine-chloromethylketone inhibitor. R110
      AP- and exopeptidase substrates are suitable indicators for coupled endopeptidase
      reactions due to their rapid cleavage and largely pH independent generation of
      intracellular fluorescence.

PMID- 7587722
TI  - Evaluation of red blood cell lysing solutions for the detection of intracellular
      antigens by flow cytometry.
AB  - When analyzing leukocyte cell surface antigens by flow cytometry, leukocytes are
      usually first labeled in whole blood and the red blood cells are finally lysed
      with lysing solutions. The erythrocytes are lysed, but the leukocytes are
      expected to remain intact. Six commercial red blood cell lysing methods were
      investigated for possible leukocyte permeabilization effect. The effectiveness of
      permeabilization was studied by propidium iodide staining, and the detectability
      of intracellular antigens was studied by using monoclonal antibodies toward two
      model antigens. Most of the lysing methods caused permeabilization of at least
      part of the leukocytes, but only one method, already found in our previous
      studies, was applicable for complete permeabilization of leukocytes and for
      detection of intracellular antigens alone or simultaneously with the cell surface
      antigens.

PMID- 7587723
TI  - Evaluation of T-lymphocyte subsets present in semen and peripheral blood of
      healthy donors: a report from the heterosexual transmission study.
AB  - The purpose of this study was to accurately determine the T-lymphocyte subsets
      found in semen from healthy volunteers, to evaluate the impact of repeated
      ejaculation on the frequency or type of immune cells present in semen, and to
      compare subset analysis in semen to that in the peripheral blood. To accomplish
      this, a flow cytometric method was developed to identify and count
      immunophenotypically distinct cells present in semen. Fresh semen samples and
      peripheral blood were collected over three consecutive days from nine healthy
      donors. Donors had normal ejaculate volume, sperm count, sperm motility,
      morphology, and leukocyte count. No significant intra-donor differences were seen
      in these parameters over time. No significant differences were observed in the
      percentage of CD3+ cells, CD4+ cells, CD8+ cells, and the CD4:CD8 ratio in semen
      on consecutive days. However, within the CD4+ subset, when naive and memory CD4+
      cells were measured, some day to day variability was suggested. No significant
      differences in CD3+, CD4+, CD8+, CD4/CD8 ratio, or naive and memory subsets were
      seen in the peripheral blood between sampling days. When semen was compared to
      peripheral blood some differences in immune subset values were observed, with an
      increase in the percentage of memory CD4+ cells in semen being the most striking.
      This finding may be relevant to HIV transmission, since others have shown that
      this cell may be preferentially infected with HIV and is the primary reservoir
      for virus in infected individuals.

PMID- 7587724
TI  - Autofluorescence correction for fluorescence in situ hybridization.
AB  - Optimal sensitivity of fluorescence in situ hybridization (FISH) requires bright
      signals and low background fluorescence. Use of locus-specific probes is
      especially dependent on high sensitivity. Some tissue preparations show high
      autofluorescence, masking small or dim signals. We have developed a new method
      for subtracting autofluorescence from digital images on a pixel-by-pixel basis.
      It is based on the observation that fluorescent labels for FISH have narrower
      excitation and emission spectra than the chemical components responsible for
      autofluorescence. Our new approach uses calculation of the ratio of
      autofluorescence between multiple color images for correction of autofluorescence
      in each individual image. By subtracting autofluorescence components, we were
      able to enhance centromeric signals and make previously indistinguishable cosmid
      signals clearly visible. This image-processing approach to autofluorescence
      correction may widen the applicability of gene-specific probes in FISH analysis
      of tumor material.

PMID- 7587726
TI  - Alterations of T-cell receptor variable region expression in human
      immunodeficiency virus disease.
AB  - Since only a small percentage of CD4+ lymphocytes is infected at any one time
      during the course of human immunodeficiency virus (HIV) disease, a question
      central to the pathogenesis of HIV is whether or not the depletion of CD4+
      lymphocytes is a random or selective event. The majority of peripheral blood T
      lymphocytes use alpha and beta variable chains as components of their T-cell
      receptor (TCR) complex. Depletion of CD4+ T lymphocytes from the peripheral blood
      may be dependent on the V beta chain expressed by the CD4+ cell, based on the
      hypothesis that HIV may encode a superantigen. Peripheral blood from normal
      controls and HIV+ patients was studied for alterations in the expression of
      various V beta chains of the TCR. Three-color flow cytometry was used to
      determine the expression of V beta 2, V beta 3, V beta 8, V beta 13, and V beta
      19 on all lymphocytes and on both CD4+ and CD8+ lymphocytes independently.
      Alteration of the V beta chains in HIV+ disease was analyzed as a function of
      absolute CD4 count and Centers for Disease Control (CDC) stage of the patient.
      These data suggest that the loss of T helper (CD4) lymphocytes during the course
      of HIV disease may be a selective event. These data are consistent with the
      hypothesis that selective depletion of CD4+, V beta 19+ lymphocytes may be due to
      the encoding of a superantigen by HIV. Furthermore, using multicolor flow
      cytometry and stratifying patients by absolute CD4 counts (or stage of disease)
      may reveal immunologic changes that might otherwise be overlooked.

PMID- 7587725
TI  - Photomultiplier voltage setting: possible important source of variability in
      molecular equivalents of soluble fluorochrome (MESF) calculation?
AB  - We evaluated the effect of flow cytometer photomultiplier (PMT) voltage setting
      on molecular equivalents of soluble fluorochrome (MESF) calculation by using two
      different quantitative microbead calibrating kits as calibrating standards and a
      third one as an unknown testing sample of stable intensity of fluorescence. Based
      on the analysis of residual values derived from linear regression and on the
      determinations of the resolution index, we demonstrated that, on a FACScan
      instrument, the window of photomultiplier setting for fluorescein isothiocyanate
      (FITC) fluorescence determinations is 590-670 V. However, the best region was in
      the range of 610-650 V. Within the 590-670 PMT voltage region, the evaluation of
      the same testing sample at different PMT voltages, at 590 V, gave MESF percentage
      differences of 15% and 13% on the two lower unknown standards of intensity
      compared to the values obtained at the nearby 630 V setting. In the analyzed PMT
      region, logarithmic amplifier response was globally maintained, whereas
      evaluation of the same unknown testing sample in both linear (Lin) and
      logarithmic (Log) amplification demonstrated (at the higher intensities of
      fluorescence) Log-Lin minimal differences within the 610-650 PMT voltage range.
      According to our data, it can be stated that PMT voltages between 610 and 650
      provide the best instrument performances and that PMT setting may be proposed as
      a source of variability in MESF calculation that deserves a careful evaluation in
      quality-control trials.

PMID- 7587728
TI  - Flow cytometry: its use in pediatric renal transplantation utilizing polyclonal
      induction.
AB  - Induction protocols for pediatric renal transplant recipients commonly utilize
      polyclonal or monoclonal agents in sequence with additional immunosuppression.
      Polyclonal agents Minnesota antilymphoblast globulin (MALG), anti-thymocyte
      globulin (ATGAM) effect both T and B cells while monoclonal agents (OKT3) are T
      cell specific. Flow cytometric analysis of T-cell subsets has become the marker
      of adequacy of immunosuppression during OKT3 therapy, yet to date no marker
      exists to measure the adequacy of immunosuppression with polyclonal agents. At
      the University of Michigan, flow cytometric analysis in pediatric renal
      transplant recipients undergoing polyclonal induction reveals that CD3, CD4, and
      CD8 suppression initially occurs. As opposed to OKT3, a rebound of CD3 cells
      occurs despite daily use of a polyclonal agent in sequence with additional
      immunosuppressives. During these analyses, a single kidney was lost which flow
      cytometry failed to predict. No significant difference in flow cytometric
      patterns occurred when comparing ATGAM to MALG induction. Flow cytometry utilized
      during polyclonal induction in pediatric renal transplant recipients revealed a
      variety of T-cell suppression patterns but failed to demonstrate persistence of
      suppression. Despite this lack of suppression as indicated by flow cytometry, a
      97% 1 year allograft survival rate exists in the pediatric transplant program at
      the University of Michigan Medical Center. Therefore, the role of flow cytometry
      during polyclonal induction has yet to be well defined.

PMID- 7587727
TI  - Evidence of a selective depletion of a CD16+ CD56+ CD8+ natural killer cell
      subset during HIV infection.
AB  - Three-color flow cytometric analysis of CD16+ natural killer (NK) cells was
      assessed in HIV seropositive patients and healthy heterosexual controls. A
      selective depletion of lymphocytes with the CD16+ NK phenotype was found among
      the HIV+ infected patients. When the CD16 lymphocyte subset was further evaluated
      by three-color flow cytometry, cells bearing both the CD8 and CD56 antigens were
      significantly decreased. Analysis of activation antigens revealed a large
      proportion of CD16+ NK cells from HIV+ patients expressed HLA-DR, but this did
      not correlate with CD25 (IL-2 receptor) expression. The overall loss of the CD8
      and CD56 antigens among the NK population with an increase in activation status
      may be due to differential loss of the NK cell subsets or, alternatively, to the
      loss of immunoregulatory cytokines, which have been shown to be important in
      maintaining NK activity. Whether these changes in the NK compartment may
      influence the outcome of individuals with HIV disease still remains an open
      question but is an important issue when performing phenotypic analysis of HIV+
      subjects.

PMID- 7587730
TI  - Variability in absolute lymphocyte counts obtained by automated cell counters.
AB  - There is increasing interest in the absolute lymphocyte count. This is partly
      driven by the need to obtain absolute values for lymphocyte subsets such as
      absolute CD4+ counts in human immunodeficiency virus (HIV)-infected persons. The
      absolute total lymphocyte count is usually determined in the routine hematology
      laboratory on a separate sample from the same patient specimen and then combined
      with percentage results from flow cytometry to obtain the absolute value of the
      lymphocyte subsets. We have studied analytic variability in the absolute
      lymphocyte determination and compared it to the variability of the total white
      blood count (WBC). In a series of 524 specimens, four different automated methods
      were compared to each other and to the traditional eye count differential. The
      automated methods were four widely used automated cell counters (Technicon H*1,
      TOA NE8000, Coulter STKS, and Abbott CD3000). The results indicate that analytic
      variability in the absolute lymphocyte counts, due, primarily, to method
      variability, is significant and is larger than the variability typically observed
      on interlaboratory trials of relative CD4 counts. These method biases cannot
      easily be reduced by calibration, since the cell classification algorithms are
      built-in features of the various cell counters. Analytic variability of the
      absolute lymphocyte counts was found to be 12.4% compared with analytic
      variability of only 4.9% for total WBC counts on the same samples. Our data
      suggest that more precise results would be obtained if flow cytometry results
      expressed each phenotype as a fraction of the leukocytes as well as total
      lymphocytes. Conversion to absolute values could then be accomplished through
      determination of the total WBC in the routine hematology laboratory.

PMID- 7587729
TI  - DNA aneuploidy in acute myeloblastic leukemia is associated with a high
      expression of lymphoid markers.
AB  - In the present study the DNA cell content of 205 de novo acute myeloblastic
      leukemia (AML) patients is analyzed at flow cytometry in order to determine both
      the incidence of DNA aneuploidy in AML patients and the clinical and biological
      characteristics of AML aneuploid cases. All technical procedures were performed
      in accordance with the proposed guidelines of the DNA Cytometric Consensus
      Conference. Our results show that the incidence of DNA aneuploidy is quite low
      (4.8%), with most cases (n = 8) hyperdiploid and only a small proportion (n = 2)
      hypodiploid. No major differences were detected between the aneuploid and diploid
      cases with respect to the clinical and prognostic disease characteristics.
      Regarding the immunophenotype of the blast cells, the aneuploid cases displayed
      both a higher incidence of immature myeloblastic phenotype and a greater
      expression of lymphoid-associated antigens. In summary, our results show that AML
      patients display a quite low incidence of DNA aneuploidy and that despite the
      fact that these cases do not display particular clinical characteristics, they
      show an association with the expression of lymphoid-related markers.

PMID- 7587731
TI  - Flow cytometric reticulocyte maturity index: a useful laboratory parameter of
      erythropoietic activity in anemia.
AB  - Flow cytometric reticulocyte analysis is superior to manual reticulocyte counting
      with respect to precision and sensitivity. Furthermore, because the fluorescence
      intensity of reticulocytes is directly proportional to the erythrocyte RNA
      content, flow cytometric analysis using thiazole orange gives a quantitative
      reticulocyte maturity index (RMI). Previous studies have demonstrated that the
      RMI parameter is the earliest indicator of bone marrow engraftment following
      transplantation. In the present study, we analyzed the correlation of the RMI to
      standard red cell parameters, reticulocyte percentage, and absolute reticulocyte
      count in 413 anemic patients. The correlation of RMI to serum erythropoietin
      (Epo) and serum transferrin receptor (TfR) was analyzed in a subset of anemic
      blood samples. We found weak correlations between the RMI and hemoglobin (r2 =
      0.041), hematocrit (r2 = 0.038), reticulocyte percentage (r2 = 0.078), and
      absolute reticulocyte count (r2 = 0.087). Stronger correlations were observed
      between the RMI and Epo (r2 = 0.181) and the TfR (r2 = 0.191). The results
      indicate that the RMI represents a cost-effective measurement of erythropoietic
      activity and provides an additional parameter to classify anemic patients into
      categories of high and low erythropoietic activity, especially in hypoproductive
      anemias.

PMID- 7587732
TI  - Idiopathic CD4+ T-lymphocytopenia: analysis of a patient with selective IgA
      deficiency and no evidence of HIV infection.
AB  - Idiopathic CD4+ T-lymphocytopenia (ICL) in HIV-seronegative patients is a newly
      described, rare entity. The common underlying abnormality is a usually stable
      depletion in CD4+ lymphocytes in patients, some of which have unexplained
      opportunistic infections. We present a previously unreported condition of an
      asymptomatic individual with CD4+ T-lymphocytopenia and a selective IgA
      deficiency. The subject is a 35-year-old healthy white male with a documented 5
      year history of low CD4+ T cell counts. He has been repeatedly HIV seronegative
      and has no risk factors for HIV infection. Data were obtained from several
      laboratories over a 5-year period and include standard WBC differentials, HIV
      testing, serum immunoglobulin quantitation, mitogen stimulation assays,
      diphtheria and tetanus antitoxin titers, and flow cytometric immunophenotyping.
      The composite results show a subject with a normal white blood cell count, an
      absolute lymphopenia, a slight granulocytosis, and a selective IgA deficiency.
      Leukocyte subset analyses show essentially normal B but significantly altered T
      cell phenotypes. The normal CD4:CD8 ratio shows extreme inversion, primarily due
      to CD4 T-lymphocytopenia.

PMID- 7587735
TI  - Fluorescence drift detection as a novel QC procedure for DNA cell-cycle analysis.
AB  - The goal of this work was to develop an objective, quantitative, and reproducible
      method of detecting fluorescence drift which may have occurred during DNA cell
      cycle data acquisition. Quality control software, "TruPloid," is described that
      analyzes list-mode files to detect and quantify fluorescence drift using three
      separate statistical tests. We show that fluorescence drift may lead to a variety
      of measurement artifacts including high coefficients of variation, obscuring of
      small populations and creation of distinct artificial peaks. Forty percent of 50
      archived list-mode files displayed fluorescence drift, which demonstrates the
      need for detection methods to deal with this source of DNA cell-cycle histogram
      artifacts.

PMID- 7587733
TI  - Assessment of aerosol containment on the ELITE flow cytometer.
AB  - Biohazardous aerosols generated during cell sorting have been of increased
      concern recently because of interest in sorting specimens containing human
      immunodeficiency virus type 1 (HIV-1). Current flow cytometers have features
      designed to contain such aerosols within the sorting chamber, but the efficacy of
      these features has not been established. Therefore, we tested aerosol containment
      by two ELITE flow cytometers (Coulter Cytometry, Inc., Hialeah, FL) during
      sorting of specimens containing high titers of bacteriophage. Agar plates
      confluent with susceptible Escherichia coli were used to detect infectious units
      released from the sorting chamber. Under recommended operating conditions very
      few infectious units were released from the sorting chambers. Release increased
      when the center stream was not optimally collected in a vacuum-exhausted tube or
      the chamber door was not completely closed. Failure of the negative pressure and
      high efficiency particle air (HEPA) filtration features had less of an effect.
      The data indicate that these standard safety features provide a rational
      expectation of safety for the flow cytometry operator.

PMID- 7587734
TI  - Immunologic differentiation of absolute lymphocyte count with an integrated flow
      cytometric system: a new concept for absolute T cell subset determinations.
AB  - We describe a method to obtain results for immune status monitoring that uses a
      three-test panel, comprised of isotype control and 2 specific Mab tests
      (CD4/CD8/CD3 and CD16/CD19/CD3), in conjunction with a flow cytometer that
      directly measures absolute counts. Automated software is used for lineage
      specific gating of three-color immunofluorescence to determine lymphocyte and
      lymphocyte subset counts. The autogating function of this software is shown to
      yield equivalent results to manual analysis by an expert user, and to be
      effective when as few as 25 target cells are present. The software is also shown
      to perform automatic quality control checks of the sample preparation, reagent,
      and automated analysis. We demonstrate that the sum of T (CD3+), B (CD19+), and
      natural killer (NK, CD16 + CD3-) cells, as a determination of all lymphocytes,
      correlates well with lymphocytes measured using a light scatter differential.
      Moreover, T + B + NK lymphocyte count is shown to be less error-prone than
      lymphocyte count from light scatter differential, and to minimize errors that
      arise from between-technician variation in sample preparation. Our data suggest
      that the new approach that we describe could offer an alternative to the
      traditional two-stage methods for measuring absolute counts of lymphocyte subsets
      for immune status monitoring. As such this method could reduce, through objective
      automated analysis, testing cost and complexity, without sacrificing the quality
      of results.

PMID- 7587736
TI  - Comparison of monoclonal antibodies for flow cytometric analysis of HLA-B27
      antigen.
AB  - HLA-B27 is an antigen associated with the disease ankylosing spondylitis. Ninety
      percent of Caucasians with ankylosing spondylitis possess the HLA-B27 antigen.
      However, only 20% of Caucasians with the HLA-B27 antigen will develop the
      disease. Defining the presence or absence of the HLA-B27 antigen can be helpful
      in differentiating ankylosing spondylitis from juvenile rheumatoid arthritis. In
      this study, we evaluated the application of two monoclonal antibodies (MoAbs),
      using flow cytometric analysis for the detection of HLA-B27 antigen. After an
      initial comparison of HLA-B27 analysis by flow cytometry to the standard
      microlymphocytotoxicity assay, cutoffs were established to differentiate HLA-B27
      positive from HLA-B27 negative. One MoAb showed very reliable results with > 99%
      accuracy in discriminating HLA-B27 positive from HLA-B27 negative samples.
      Various parameters were investigated to obtain the optimum results and showed
      that incubation time, reagent lot, and the flow cytometric instrument can affect
      the results. We concluded that a reliable MoAb and flow cytometry are valuable
      for the rapid and inexpensive determination of HLA-B27 typing in the clinical
      setting. However, testing conditions can affect the accuracy of results;
      therefore, adequate parallel testing in various conditions must be performed in
      order to establish the proper standards.

PMID- 7587737
TI  - CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme
      immunoassay.
AB  - Assessment of the CD4 lymphocyte number, currently performed by flow cytometry,
      is one of the main laboratory tests for establishing progression to acquired
      immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been
      commercialized which can be very useful for counting CD4 cells in laboratories
      where flow cytometers are not available. In the present study, a comparative
      evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay
      was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human
      immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001),
      and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis
      (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not
      found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05,
      not significant). Some differences could be found at low CD4 lymphocyte levels
      since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the
      whole blood sample could cause overestimation of CD4 cell numbers by the enzyme
      assay.

PMID- 7587739
TI  - Pitfalls in determining the mean peak channel value for the diploid G0/1 DNA peak
      in solid tissue.

PMID- 7587738
TI  - Urinary sediment analyzed by flow cytometry.
AB  - A flow cytometer for the automated analysis of urinary sediment was designed, and
      its performance was examined by the evaluation of 821 specimens. Auramine O, a
      dye for DNA and RNA, was used for the staining of the sediment. Urine (5 ml or
      more) was processed by the instrument for sediment analysis. Conventional
      microscopic analysis was done for comparison. The RBC count, the WBC count, and
      the number of bacterial cells, epithelial cells, and casts found by the flow
      cytometer and by microscopy were compared. Correlation was high for all these
      results. The overall sensitivity, specificity, and efficiency (accuracy) in the
      items analyzed were 84.7%, 57.8%, and 67.2%, respectively. One hundred specimens
      could be analyzed by the instrument per hour. The instrument seemed useful for
      screening for urinary tract disorders to identify specimens that should be
      analyzed microscopically in routine laboratories.

PMID- 7587741
TI  - Expression of the Fas antigen in patients infected with human immunodeficiency
      virus.
AB  - Lymphocytes from patients with HIV infection have been shown to undergo
      accelerated apoptosis. Fas antigen is a cell surface protein known to initiate an
      apoptotic signal. Therefore, we undertook a study to examine the expression of
      the Fas antigen during HIV infection. Using three color flow cytometry,
      expression of the Fas antigen on lymphocytes of 23 HIV infected individuals (CDC
      category 2, CD4 200-499 cells/microL, n = 10; CDC category 3, CD4 < 200
      cells/microL, n = 13) and 10 healthy controls was examined. Both CD3+CD4+ and
      CD3+CD8+ subsets were examined for their expression of this marker. In
      lymphocytes of healthy controls, 47% of the CD3+CD4+ and 45% of the CD3+CD8+
      cells were Fas antigen positive. This percentage was significantly increased in
      CD4 cells from HIV infected patients belonging to CDC category 3, but was
      unchanged from normal values in CDC category 2 subjects. The increase in the
      percentage of CD4+ T cells expressing Fas antigen in patients correlated
      significantly with the decrease in circulating CD4 T cell count (P < 0.009). In
      addition, by examining mean fluorescence intensity, we found that the amount of
      Fas expression per cell was increased threefold in CD3+CD4+ cells and increased
      twofold in CD3+CD8+ cells in category 3 patients. These results demonstrate that
      an increase in Fas antigen expression occurs during HIV infection.

PMID- 7587740
TI  - Alterations in phenotype and cell-surface antigen expression levels of human
      monocytes: differential response to in vivo administration of rhM-CSF or rhGM
      CSF.
AB  - We investigated, via multicolor flow cytometry, the in vivo effects of colony
      stimulating factors (CSFs) on cell size, frequencies, and expression of surface
      antigens on peripheral blood monocytes from melanoma patients treated
      concurrently with CSFs and tumor-specific monoclonal antibody (mAb) R24.
      Recombinant human macrophage colony-stimulating factor (rhM-CSF) increased cell
      size, relative percentages of monocytes, percentages of CD14+, HLA-DQ+, CD11b+,
      and CD16+ monocytes, and cell-surface expressions of HLA-DR and CD11b; rhM-CSF
      also up-regulated cell-surface expression of CD14 on CD14brightCD16- monocytes.
      Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      increased cell size, percentages of CD14+, HLA-DQ+, and CD11b+ monocytes, and
      cell-surface expressions of HLA-DR, HLA-DQ, CD11b, and CD58. Relative percentages
      of monocytes and CD16+ cells and cell-surface expression of CD14 on
      CD14brightCD16- monocytes decreased. In addition, monocytes derived from patients
      treated with rhM-CSF showed functional activity when assayed in vitro for
      antibody-dependent cellular cytotoxicity (ADCC). During treatment and coincident
      with increased CD16 expression, monocytes derived from rhM-CSF patients had
      enhanced levels of cytotoxicity towards melanoma target cells compared to healthy
      controls and to patients treated with rhGM-CSF.

PMID- 7587742
TI  - Reproducibility in DNA flow cytometric analysis of breast cancer: comparison of
      12 laboratories' results for 67 sample homogenates.
AB  - Flow cytometric (FCM) DNA analysis yields information on ploidy status and the S
      phase fraction (SPF), variables of prognostic importance in breast cancer. The
      clinical value of the SPF is currently being evaluated in prospective randomized
      trials. The widespread use of FCM DNA analysis emphasizes the importance of
      reproducibility (both intra- and interlaboratory). In this study, 67 nuclear
      suspensions of breast cancer samples were analyzed by 12 laboratories routinely
      performing FCM DNA analysis in breast cancer. No general guidelines were imposed;
      each laboratory used its own standard protocols. For DNA ploidy status (diploid
      vs. non-diploid), agreement was complete for 79% (53/67) of the samples, compared
      with 64% (43/67) of samples when tetraploidy was considered [i.e., euploid
      (diploid+tetraploid) vs. aneuploid (the remaining non-diploid)]. For the SPF,
      pairwise comparison of the results of all 12 laboratories yielded a mean
      Spearman's rank correlation of 0.78 (range: 0.54-0.93). For those 39 samples
      being categorized in low or high SPF by all laboratories, all agreed in 14
      samples (36%). Similar patterns were obtained with kappa measures, agreement
      being good for ploidy status (diploid vs. non-diploid; overall kappa = 0.87 and
      0.74 for euploid vs. aneuploid), but moderate for the SPF [overall kappa = 0.47
      (for low SPF vs. high SPF vs. "no SPF reported")]. Discrepancies were chiefly
      attributable to differences in the categorization of the S-phase values, rather
      than in FCM procedures, other critical differences being in the detection and
      interpretation of near-diploid and small non-diploid cell populations, the
      definition of tetraploidy, and the choice and execution of the method used for S
      phase estimation. Based on the observations of this study, detailed guidelines
      for FCM analysis and interpretation of data are proposed in the Appendix. Some
      issues remain, however, e.g., to standardize a method for S-phase calculation and
      tetraploid definition.

PMID- 7587744
TI  - Flow cytometric and clinicopathologic study of 197 hydatidiform moles with
      special reference to the significance of cytometric aneuploidy and literature
      review.
AB  - In order to evaluate the significance of cytometric aneuploidy in molar
      placentas, we analyzed 197 hydatidiform moles by flow cytometry using formalin
      fixed, paraffin-embedded tissues. Of 150 complete moles (CMs), 110 were diploid,
      26 were tetraploid, and 14 were aneuploid (non-triploid/tetraploid aneuploid). Of
      47 partial moles (PMs), 44 were triploid and 3 were diploid. We could not find
      any histologic differences among the diploid, tetraploid, and aneuploid CMs. We
      found that flow cytometric DNA analysis was very helpful to differentiate CM from
      PM. Persistent diseases developed in 12 of 69 CMs (17.4%) (9 of 47 diploid and 3
      of 14 tetraploid CMs) and in none of 26 PMs (0%). Four diploid and 2 tetraploid
      CMs were invasive and one each with diploid and tetraploid CM developed
      choriocarcinoma and none of 8 aneuploid CMs had sequelae; however, there was no
      correlation between DNA ploidy and clinical outcome in the CMs. These results
      suggest that cytometric aneuploidy (non-diploidy) in CMs is not an independent
      predictor of persistent disease.

PMID- 7587743
TI  - Peripheral blood cell preparation influences the level of expression of leukocyte
      cell surface markers as assessed with quantitative multicolor flow cytometry.
AB  - We have compared the influence of sample preparation upon the level of surface
      expression of T, B, and NK cell-related antigens as assessed by flow cytometry.
      Lysed whole blood (WBL), Ficoll-Paque separated peripheral blood lymphocyte (F
      PBL), and frozen peripheral blood lymphocyte (Fr-PBL) were analyzed via single-
      and multicolor flow cytometry. The percentage of positive cells expressing the
      individual cell surface markers was not affected by the procedure for preparation
      of WBL, F-PBL, and Fr-PBL. In contrast, the fluorescence intensity level of
      individual cell surface markers varied depending on cell preparation. By using
      Quantum Simply Cellular (QSC) microbeads, the antibody binding capacity (ABC) of
      single-color stained cells was quantified and compared. The amount of monoclonal
      antibody (MAb) anti-CD3-FITC bound to Fr-PBL (mean ABC = 137,040) was
      significantly higher (P < 0.001) that the amounts bound to WBL (mean ABC =
      112,410) and F-PBL (mean ABC = 107,738). In multicolor analysis, the fluorescence
      intensity of CD3-FITC and CD4-FITC was significantly higher on Fr-PBL than on WBL
      and F-PBL; CD8-PE and CD20-PerCP was significantly higher on WBL. Furthermore,
      the intensity of CD3 and CD4 was different on T-cell subsets. The intensity of
      CD3 staining in three-color analysis was lower than with single-color staining
      using the same fluorochrome. We conclude that particularly the method of cell
      preparation but also the selection of MAb combinations may influence the level of
      staining of certain lymphocyte antigens. This may be of relevance in the analysis
      of cellular activation and regulation of differentiation.

PMID- 7587745
TI  - CD 45 gating correlates with bone marrow differential.
AB  - In this study we assess a flow cytometric gating method and its correlation with
      a concurrent manual bone marrow differential in abnormal marrows. Like normal
      bone marrow cells, leukemic blasts fall into discrete areas when a cytogram of CD
      45 expression and Right Angle Light Scatter is plotted in Log scale. We studied
      50 specimens with a suspected diagnosis of leukemia. Gates were set on the eight
      discrete clusters typically found in normal bone marrow. We employed these gates
      to determine the differential of the abnormal bone marrows. Our results show a
      high correlation between the flow differential and the manual differential with
      the following r values: blasts 0.875; promyelocytes 0.914; myeloid precursors
      0.879; neutrophils 0.776; lymphocytes 0.707; monocytes 0.913; and erythroid
      precursors 0.873. In addition some leukemic infiltrates appear to produce a
      characteristic pattern with the CD 45 vs. RALS cytogram. In this study, there is
      a total of 6 cases (3 false positives and 3 false negatives) where the flow
      differential does not render the same diagnosis as the manual differential, and 4
      cases in which there is evidence of marked peripheral contamination leading to
      disagreement between the two methods. This method provides a relatively easy and
      powerful tool which can be applied to all bone marrow specimens that undergo flow
      cytometric analysis. It can greatly enhance the identification and lineage
      assessment of leukemic blasts in the bone marrow. The correlation with a manual
      differential is high, and this gating method may provide an inexpensive and easy
      means of obtaining an automated bone marrow differential.

PMID- 7587746
TI  - HLA-B27 screening by flow cytometry.
AB  - A flow cytometric assay for lymphocyte HLA-B27 expression using a two-color
      direct immunofluorescent assay was compared to traditional
      microlymphocytotoxicity testing on 209 clinical samples. For the flow cytometric
      assay, whole blood was mixed with a monoclonal anti-B27 conjugated to fluorescein
      isothiocyanate (FITC) and anti-CD3 conjugated to phycoerythrin (PE). The samples
      were analyzed with flow cytometry by gating on CD3 positive events and anti-B27
      staining intensity was evaluated as median channel fluorescence of the histogram
      peak. The median channel fluorescence was least with B27 negative and B7 negative
      samples (84 +/- 17), intermediate with samples that were B27 negative but B7
      positive (118 +/- 13), and greatest with samples that were B27 positive (155 +/-
      13). In addition to cross-reactivity with the B7 antigen (n = 38), the monoclonal
      anti-B27 cross-reacted with HLA-B37 positive samples (n = 3) and HLA-B39 positive
      samples (n = 3). Using a median channel fluorescence cutoff of 136, 39 of the 40
      B27 positive samples gave positive results in the flow cytometric assay for a
      sensitivity of 97.6%. The specificity was 95.9% with 7 false positives of 169 B27
      negative samples. The flow cytometric HLA-B27 assay is a convenient, useful
      screening test. For greatest specificity, samples positive by flow cytometry
      should be confirmed by conventional microlymphocytotoxicity or by use of other
      monoclonal antibodies directed against B27.

PMID- 7587747
TI  - Lymphocyte subset determination using a hematology analyzer.
AB  - Anti-CD4 antibody (T4)-coated microspheres were used to label CD4 cells in whole
      blood. The mixture was lysed and analyzed by a modified Coulter VCS hematology
      analyzer, which differentiated microsphere-labeled cells by a change in Coulter
      volume, conductance, and light scatter. %CD3+/CD4+ fluorescent values from a
      profile were compared to %CD4 values using the VCS-microsphere method. CD3 gating
      was used to exclude CD4+ monocytes from the 90LS-FALS lymphocyte gate. The
      results correlated well (R = 0.996). The percentage of CD4+ lymphocytes from
      profile scatterplots and VCS scatterplots showed a line of regression close to
      the equivalence line (n = 76, slope = 0.96) when CD3 gating was used for the
      profile. These results suggest that CD3 gating, though necessary for 90LS-FALS
      scatterplots, may not be necessary for volume-conductance-light scatterplots.

PMID- 7587748
TI  - Amphotericin B susceptibility of Candida species assessed by rapid flow
      cytometric membrane potential assay.
AB  - A method for detection of the susceptibility of Candida species to amphotericin B
      is described. The technique is a modification of a similar flow cytometric
      technique designed to detect antibiotic susceptibility of Staphylococcus aureus.
      Membrane potential changes caused by the antibiotic are measured flow
      cytometrically by using the fluorescent membrane potential-sensitive dye 3,3'
      dipentyloxacarbocyanine iodide. One strain each of C. albicans and C. tropicalis
      (both sensitive to amphotericin B) and one strain of C. tropicalis (resistant to
      amphotericin B) were used to validate the method. Sensitivity or resistance was
      easily determined after 30 min of incubation in the presence of the antibiotic,
      and the drug effect was evident in a dose-dependent manner.

PMID- 7587749
TI  - False DNA aneuploidy possibly caused by viral DNA.

PMID- 7587750
TI  - Heterogeneity of malignant tumors should be considered when performing flow
      cytometric DNA analysis.

PMID- 7587752
TI  - Immunophenotyping of congenital leukemia.
AB  - Congenital leukemia is a rare but well-documented disease in which a leukemic
      process is detected at birth or very shortly thereafter. An estimated 175-200
      reports of congenital leukemia have appeared in the literature. The majority of
      the cases reported have not undergone thorough immunophenotyping, but rather have
      been assigned lineage based on cytochemical and morphological studies.
      Historically, a large proportion of congenital leukemias have been thought to be
      of the myeloid lineage, in contrast to pediatric leukemias in general, which are
      primarily lymphoid. The precise proportions of the lineage assignments may be
      distorted by the inclusion of cases of transient myeloproliferative disorders
      (TMD) as congenital leukemia. The immunophenotyping data available to date
      suggest that congenital leukemias are phenotypically heterogeneous, lacking any
      common distinguishing markers. The prognosis for congenital leukemias is usually
      poor if leukemoid reactive processes, such as TMD, are carefully excluded.

PMID- 7587753
TI  - Congenital leukemia: report of two cases.
AB  - Congenital leukemia is a rare disease in which a leukemic process is present at
      birth or immediately thereafter. The majority of cases presented in the
      literature were reported prior to the availability of contemporary
      immunophenotyping methods, and lineage assignment was often made on the basis of
      morphology alone. Congenital leukemias may be of various lineages, although,
      historically, monocytic and myelomonocytic congenital leukemias appear to be the
      most prevalent. We present two cases of congenital leukemia with detailed
      immunophenotypic and cytochemical characterization. One case is of the lymphoid
      lineage, and the second is of myelomonocytic lineage. Neither patient displayed
      trisomy 21.

PMID- 7587754
TI  - Prognostic significance of DNA content in bladder cancer based on flow cytometric
      analysis of 249 transitional cell carcinomas.
AB  - The prognostic significance of DNA index (DI), S-phase fraction, and
      heterogeneity determined by flow cytometric DNA analysis was assessed in a
      prospective study of 249 newly diagnosed transitional cell carcinomas of the
      bladder. The median observation time was 4.8 years. A total of 456 subpopulations
      were detected. The S-phases could be estimated in 299 subpopulations. A DI > 1.25
      or an S-phase above 9.7% were strongly correlated to invasiveness. One hundred
      and ten patients were treated with transurethral resection (TUR). Relapse-free
      survival could not be predicted by the DNA-derived parameters. Univariate
      analysis of survival showed prognostic significance of diploidy (0.98 < DI < or =
      1.02, P = 0.02), hypotetraploidy (1.50 < DI < or = 1.96, P = 0.002), and S-phase
      size (P = 0.008). Multivariate analysis pointed to the T-classification (RR =
      1.64) and hypotetraploidy (RR = 1.57) as prognostic parameters for survival of
      TUR-treated patients. One hundred and thirty-nine patients received radiotherapy
      (RT). A significantly better response was found for tumors with a subpopulation
      with a hypertetraploid DNA content (DI > 2.04, P = 0.05), and a significantly
      worse response for subpopulations with a maximum S-phase > 24.5% (P = 0.04). T
      classification and histological grade had no predictive value. A logistic
      regression analysis indicated an estimated probability of response to RT of 77%
      for tumors with a DI > 2.04 and an S-phase < 24.5%, whereas tumors with a DI <
      2.04 and an S-phase > 24.5% had only a 28% probability of response. The poor
      response to RT, predicted by an S-phase > 24.5%, translated into a poor survival,
      whereas the better treatment response found for patients with a DI > 2.04 did not
      result in a longer survival. Multivariate analysis pointed to S-phase (RR =
      1.70), T-classification (RR = 1.60), and grade (RR = 0.65) as independent
      prognostic parameters for survival of RT-treated patients.

PMID- 7587757
TI  - Effect of intervention in inflammatory bowel disease on health-related quality of
      life: a critical review.
AB  - Health-related quality of life (HRQOL) is a quantitative measurement of
      subjective perception of health state, including emotional and social aspects. It
      can be reliably measured with several valid instruments. Previous reviews of the
      literature suggested inadequate attention to HRQOL in studies of interventions in
      inflammatory bowel disease. PURPOSE: This study was undertaken to assess the
      current status of the quality of measurement of HRQOL in studies of inflammatory
      bowel disease and to review the clinical conclusions warranted by the literature.
      METHOD: Medicine was searched for articles relating to ulcerative colitis,
      Crohn's disease, or inflammatory bowel disease and quality of life since 1981.
      The articles found were reviewed for citations of further articles. The adequacy
      of HRQOL measure was assessed and graded, and the study design was categorized to
      assess the strength of the literature on the whole. RESULTS: A trend was found
      toward higher quality of HRQOL measurement in the period 1988 to 1994 compared
      with 1981 to 1987. Most of the improvement was because of increased use of
      standardized and multidomain but unvalidated and unpublished questionnaires for
      measurement. CONCLUSIONS: Confidence in the following clinical conclusions in
      studies of surgical interventions in inflammatory bowel disease is limited by
      study design: that pelvic pouch is not inferior to ileostomy, that specific
      domains of HRQOL are differentially affected by different surgical procedures,
      and (with less confidence) that surgery is helpful in Crohn's disease. Medical
      studies have demonstrated that high quality HRQOL measures can be integrated into
      randomized, prospective trials. Clinically equivalent treatments have shown
      differential effects or HRQOL: 9 mg daily of budesonide is superior to 15 mg, and
      hydrocortisone foam enemas are superior to prednisolone. Home parenteral
      nutrition has received modest support, limited again by study design. It is
      recommended that standard tests of HRQOL be used to increase comparability of
      studies and to increase the quality of this literature in general. In particular
      the Inflammatory Bowel Disease Questionnaire, Rating Form of Inflammatory Bowel
      Disease Concerns, and Direct Questioning of Objectives are recommended.

PMID- 7587755
TI  - Anal fissure in Crohn's disease: a plea for aggressive management.
AB  - PURPOSE: This study was undertaken to identify clinical characteristics, natural
      history, and results of medical and surgical treatment of anal fissures in
      Crohn's disease. METHODS: This is a retrospective review of patients with Crohn's
      disease and anal fissure. RESULTS: Of the 56 study patients, 49 (84 percent) had
      symptomatic fissures. Fissures were most commonly (66 percent) located in the
      posterior midline, and 18 patients (32 percent) had multiple fissures. Fissures
      healed in one-half of patients treated medically. Factors predictive of
      successful medical treatment included male gender, painless fissure, and acute
      fissure. Of 15 patients, 10 (67 percent) treated surgically healed. Fissures in
      seven of eight patients (88 percent) who underwent anorectal procedures healed
      compared with fissures in only three of seven patients (43 percent) who underwent
      proximal intestinal resection. In the group of 50 patients with complete follow
      up studies, an anal abscess or fistula from the base of an unhealed fissure
      developed in 13 patients (26 percent). More fissures healed after anorectal
      surgery (88 percent) than after medical treatment alone (49 percent; P = 0.05) or
      after abnormal surgery (29 percent; P = 0.03). CONCLUSION: This series documents
      that unhealed fissures frequently progress to more ominous anal pathologic
      disease. Judicious use of internal sphincterotomy appears to be safe for fissures
      unresponsive to medical treatment.

PMID- 7587751
TI  - Analysis of heterogeneity in human tumors: a unique role for flow and image
      cytometry?

PMID- 7587756
TI  - Paradoxical puborectalis contraction in patients after pelvic pouch construction.
AB  - Normal defecation is associated with relaxation of sphincters during the
      evacuation process. However, obstructive defecation is sometimes seen clinically
      manifested by abnormal contraction of the puborectalis during defecation rather
      than relaxing. This condition has not previously been described after pelvic
      pouch construction. PURPOSE: This study was done to evaluate patients for
      defecation difficulties caused by paradoxical puborectalis contraction after
      pelvic pouch procedures. METHODS: Prospectively, patients with defecation
      difficulties were questioned. They then underwent electromyography if they met
      particular criteria. Biofeedback was offered to all patients demonstrating
      paradox on electromyography. Follow-up was by clinic visits and interviews.
      RESULTS: After pelvic pouch construction, 13 patients were found to have
      paradoxical puborectalis contraction. Twelve of 13 patients elected to have
      biofeedback therapy. Eleven of these 12 were available for follow-up an average
      of eight (1-15) months after biofeedback. Nine improved, and two had no change in
      their defecation difficulty. Of the initial 13, 10 had an event, either pouchitis
      or abdominal trauma, directly before their defecation problems. CONCLUSION:
      Paradoxical puborectalis contraction can occur in patients after pelvic pouch
      surgery. It should be suspected in patients with defecation difficulties in the
      absence of an anatomic abnormality. Biofeedback is effective treatment.

PMID- 7587758
TI  - Patterns of recurrence after nerve-sparing surgery for rectal adenocarcinoma with
      special reference to loco-regional recurrence.
AB  - PURPOSE: Since the early 1980s to relieve functional disturbances after rectal
      excision, we have been performing nerve-sparing surgery for rectal cancer. The
      aim of this study was to analyze patterns of recurrences, especially concerning
      causes of local ones. Furthermore, we would like to address the criteria we used
      in patient selection to effect successful nerve-sparing surgery. METHODS: From
      1982 to 1991, 306 patients underwent nerve-sparing operations, which may be
      categorized into three types: 1) total autonomic nerve preservation (125 cases),
      2) complete pelvic nerve preservation (105 cases), and 3) partial pelvic nerve
      preservation with removal of parasympathetic nerve (79 cases). Single and
      multivariant regression analyses were conducted to investigate patterns of
      recurrence, especially causes of local ones. RESULTS: Sixty-five patients (21
      percent) developed recurrent tumors, 19 of which (6.2 percent) were local. Using
      Dukes terms, there were five patients with Dukes A 13 with Dukes B, and 47 (35
      percent) with Dukes C stages. Rate of local recurrences was 13 percent in
      patients with Dukes C tumor. According to single-variant analysis of Dukes C
      patients, the following factors are thought to influence local recurrences:
      number of lymph nodes metastases, level of primary growth, and direction of
      lymphatic spread. Multivariate regression analysis suggested that lymph node
      metastasis was the most important and influencing factor on local regrowth (P <
      0.002). CONCLUSIONS: Compared with local recurrences is so-called extended
      surgery appeared to be lower. Our current policy is aggressive application of
      nerve-sparing surgery, even to patients with node-positive rectal cancer, taking
      into consideration the exact extent of cancer spread. From the viewpoint of
      neuroanatomy related to mesorectum, we discussed patient determination for our
      nerve-sparing surgery.

PMID- 7587759
TI  - Anorectal surgery in human immunodeficiency virus-infected patients. Clinical
      outcome in relation to immune status.
AB  - PURPOSE: Anorectal disease is commonly found in human immunodeficiency virus
      (HIV)-infected patients. The aim of this study was to determine the spectrum of
      anorectal disease, its surgical treatment, clinical outcome, and its relation to
      immune status. METHODS: Medical records of all HIV-infected patients with
      anorectal pathology that required surgical treatment from January 1984 to January
      1994 were retrospectively reviewed. Patients were divided into five different
      groups: common anorectal pathology (hemorrhoids, polyps, Group A); condylomata
      acuminata (Group B); perianal sepsis (abscesses, fistulas, Group C); anorectal
      ulcers (Group D); malignancies (Group E). RESULTS: Eighty-three patients needed
      204 surgical consultations (13 percent conservative, 87 percent operative) for
      170 anorectal diseases. Fifty-one patients had multiple anorectal pathology.
      Operative intervention resulted in adequate wound healing and symptom relief in
      59 percent of patients, adequate wound healing without relief of symptoms in 24
      percent of patients, and disturbed wound healing was related to type of anorectal
      disease (P < 0.001) and to preoperative CD4(+)-lymphocyte counts (P < 0.01).
      Disturbed wound healing and most insufficient immune status were encountered in
      Groups C, D, and E. Within these groups low CD4(+)-lymphocyte counts were a risk
      factor for disturbed wound healing (P = 0.004). Median postoperative survival was
      highest (4.7 years) in Group A, lowest (0.6 years) in Groups D and E, and related
      to type of anorectal disease (P = 0.0001). CONCLUSIONS: The spectrum of anorectal
      disease is complex. Type of anorectal disease is strongly related to immune
      status, wound healing, and postoperative survival.

PMID- 7587760
TI  - p53 nuclear overexpression may not be an independent prognostic marker in early
      colorectal cancer.
AB  - PURPOSE: This study was designed to determine if p53 nuclear overexpression, as
      detected by immunohistochemistry, is a marker of prognostic significance in early
      (Stage I) colorectal cancer (CRC). METHODS: Tissue sections obtained from
      archival blocks of 66 patients with surgically treated Stage 1 CRC were stained
      immunohistochemically for p53 using a monoclonal antibody (PAB 1801-Ab2).
      Differences in survival between p53 positive (p53+) and p53 negative (p53-)
      groups were compared using Kaplan-Meier survival curves and the log-rank test.
      RESULTS: Thirty-four patients (51.5 percent) were p53+ and 32 (48.5 percent) were
      p53-. There were significantly more p53+ tumors in females (23 of 34) compared
      with males (11 of 34) (P = 0.01). Follow-up ranged from 1 to 128.5 (mean, 44.7;
      median, 38.2) months. Thirteen patients (19.7 percent) developed recurrence, of
      whom five died of disease. Univariate analysis of clinical and pathologic
      variables did not reveal my statistically significant differences between p53+
      and p53- tumors. Mean actuarial survival was longer (48.2 months) in the p53-
      group compared with the p53+ group (41.5 months). However, comparison of survival
      curves using the log-rank test did not show a statistically significant
      difference in survival (log-rank chi-squared = 0.2; P = 0.6). CONCLUSION: p53
      nuclear overexpression does not appear to be an independent marker of prognostic
      significance in surgically treated early CRC. Females were more likely to have
      p53+ tumors. The biologic significance of this findings is unknown.

PMID- 7587761
TI  - Impact of pneumoperitoneum on trocar site implantation of colon cancer in hamster
      model.
AB  - BACKGROUND: Numerous anecdotal reports have documented the spread of colon cancer
      to trocar sites after laparoscopic-assisted colectomy. We hypothesized that the
      pneumoperitoneum of laparoscopy potentiated tumor adherence to trocar sites.
      PURPOSE: This study was designed to determine the effect of CO2 pneumoperitoneum
      on the rate of tumor implantation at trocar sites. METHODS: Viable GW-39 human
      colon cancer cells were injected into the abdominal cavity of hamsters (2 x 10(6)
      cells/hamster). A midline laparotomy, insertion of four 5-mm trocars, injection
      of viable cells into the mesentery of the cecum, and free peritoneal cavity was
      performed in two groups: one control group (41) who did not receive a
      pneumoperitoneum and a comparison group (50) who underwent pneumoperitoneum for
      ten minutes at an insufflation pressure of 10 mmHg. Animals were killed at six
      weeks, and hematoxylin and eosin-stained sections of trocar wounds, midline
      wound, small intestine, cecum, liver, and lung were examined by a veterinary
      pathologist, who was blinded to operation. RESULTS: Pneumoperitoneum increased
      tumor implantation in the cecal mesentery and the midline incision (P < 0.05) but
      did not effect recurrence in the liver, lung, or jejunum. Trocar site
      implantation tripled with the addition of pneumoperitoneum increased implantation
      of pneumoperitoneum (26 vs. 75 percent) (P < 0.0001). CONCLUSION:
      Pneumoperitoneum increased implantation of free intra-abdominal cancer cells at
      wound sites on the abdominal wall or within the abdominal cavity in this animal
      model. The use of pneumoperitoneum during laparoscopy in patients with colon
      cancer should only be performed in a protocol setting to evaluate the effect of
      pneumoperitoneum on the treatment of cancer.

PMID- 7587762
TI  - Primary signet-ring cell carcinoma of the colon and rectum.
AB  - PURPOSE: Colorectal signet-ring cell carcinoma (SRCC) is uncommon; discordant
      data have been previously reported about clinicopathologic features. Thirty-four
      cases of primary colorectal SRCC were retrospectively reviewed to clarify
      controversies. METHODS: Primary colorectal SRCC was diagnosed when the following
      criteria were satisfied: 1) the tumor was primary; 2) histologic material was
      adequate; 3) signet-ring cell represented more than 50 percent of the cancer.
      RESULTS: We identified 34 cases (1.1 percent) of 2,995 consecutive large bowel
      cancers collected at the Institute of Anatomic Pathology of Florence between 1985
      and 1993. Patients ranged in age from 31 to 89 (mean, 63.5; median, 65) years; 19
      were male, and 15 were female (male:female = 1.3:1). Fifteen tumors were located
      in the proximal colon, 11 in the rectum, and 8 in the distal colon. The gross
      shape was infiltrative in 24 cases and exophytic in 10; only 6 cases (17.6
      percent) showed features of linitis plastica. Most cancers (61.8 percent) were
      Stage C, 29.4 percent were Stage B, and distant metastases were present in only
      three cases (8.8 percent). No Stage A case was found. Prognosis was extremely
      poor, and overall five-year survival rate was 9.1 percent. Survival was
      influenced significantly by tumor stage (P < 0.01). CONCLUSIONS: Comparison of
      our data with the literature showed many differences that could be related to
      different applied diagnostic criteria. We underlined the importance of histology
      as reproducible criterion for diagnosis of primary colorectal SRCC.

PMID- 7587763
TI  - Long-term follow-up of local excision and radiation therapy for invasive rectal
      cancer.
AB  - PURPOSE: Little is known regarding the long-term outcome of patients with rectal
      cancer treated by local excision and radiation therapy. We updated our
      institutional experience with this approach. METHODS: From January 1986 to
      December 1991, 23 patients (median age, 64 (range, 30-80) years) with mobile,
      moderately differentiated adenocarcinoma of the rectum were offered transanal
      excision. Two patients with large T3 tumors, who were judged intraoperatively to
      be unsuited for a local procedure, received radical resection and were excluded
      from analysis. Twenty-one patients underwent transanal excision en bloc (14) or
      piece-meal (7) through a resectoscope. Seven patients (74 percent) had either
      extensive medical problems or refused a colostomy. Patients received a median of
      5,040 cGy postoperatively, and 15 also received 500 cGy preoperatively on
      protocol. Two patients received concomitant chemotherapy. Median follow-up is 56
      months for all patients and 67 months for survivors (range, 27-92 months).
      RESULTS: There were 2 T1, 15 T2, and 4 T3 tumors. The distance from the anal
      verge was a median of 4 (range, 1-7) cm. The median tumor size was 3 (range, 2-7)
      cm. Sixteen patients had more than one-third of the wall involved. Four patients
      (19 percent) developed a local recurrence at 26, 30, 33, and 48 (median, 31.5)
      months. Three were salvaged (abdominoperineal resection = 2; low anterior
      resection = 1) and remain disease-free 18, 36, and 37 months postoperatively.
      Four patients (19 percent) developed metastases (lung = 3; liver = 1) at 3, 22,
      25 and 44 months after initial treatment (median, 23.5 months). The actuarial
      five-year overall, disease-free and recurrence-free survival are 77, 75, and 58
      percent, respectively. Twelve patients (57 percent) have no evidence of disease
      while retaining their rectum. There was one postoperative death. CONCLUSIONS:
      Long-term follow-up confirms that local excision and radiation therapy is of
      value in patients with mobile tumors of the rectum. It suggests that this
      treatment can be offered to those patients who refuse a colostomy or are
      medically compromised and may be an acceptable option for selected patients with
      T2 or T3, mobile adenocarcinomas of the rectum.

PMID- 7587764
TI  - Collagen structural organization of healing colonic anastomoses and the effect of
      growth hormone treatment.
AB  - PURPOSE: This experimental study was designed to investigate the collagen fibrils
      of colonic anastomoses in rats and to compare normal healing with rats treated
      with biosynthetic growth hormone (bGH). METHODS: The healing zone of left colonic
      anastomoses was studied at days 2, 4, and 6 after surgery by means of scanning
      electron microscopy. RESULTS: After four days of healing a normal anastomosis was
      filled with loosely packed and unorganized collagen fibrils, which were organized
      into collagen fibers after six days. Compared with normal anastomoses, rats
      treated with bGH showed a more organized healing, characterized by a dense
      structure of a new-formed collagen framework of fibrils and immature collagen
      fibers after six days. CONCLUSIONS: Healing colonic anastomoses are characterized
      by new-formed collagen fibrils at postoperative day 4, and bGH seems to stimulate
      structural organization of the anastomotic collagen fibrils into fibers.

PMID- 7587765
TI  - Multiple vaginal deliveries increase the risk of permanent incontinence of flatus
      urine in normal premenopausal women.
AB  - PURPOSE: This study was undertaken to evaluate the risk of permanent flatus or
      urinary incontinence after repeated vaginal deliveries. METHODS: In 1989 a
      questionnaire on obstetric history and urinary and fecal incontinence was sent to
      a sample of 304 women selected from the birth records from 1976 to 1988; 242
      responded (80 percent). RESULTS: Participants had one, two, or three vaginal
      deliveries, all without an obstetric tear of the anal sphincter. After the first,
      second, and third deliveries, 1.2, 1.5, and 8.3 percent developed permanent
      flatus incontinence. The risk was significantly increased after the third
      delivery compared with the first and second deliveries (odds ratio, 6.6;
      confidence interval, 2.4-18.3). Permanent urinary incontinence after the first,
      second, and third delivery developed in 3.3, 1.0, and 6.8 percent. The risk was
      significantly increased after the third delivery compared with the first and
      second (odds ratio, 3.2; confidence interval, 1.1-9.1). CONCLUSION: These results
      indicate that repeated vaginal deliveries increase the risk of minor anal and
      urinary incontinence, which were found to be a common problem in premenopausal
      women.

PMID- 7587766
TI  - Colorectal complications following cardiac surgery. Six-year experience.
AB  - PURPOSE: This study was undertaken to assess colorectal complications following
      cardiopulmonary bypass surgery. METHOD: This is a retrospective review of 5,801
      patients who underwent 5,801 cardiopulmonary bypass procedures from 1985 to 1991.
      Patients were evaluated for type of bypass procedure, postoperative colorectal
      complications, age, sex, bypass time, aortic cross-clamp time, elective vs.
      emergency cases, uses of intra-aortic balloon pump, perioperative hypotension,
      and use of vasopressors. Statistical analysis was performed using chi-squared
      analysis and Student's t-test. RESULTS: Nineteen of the 5,801 patients developed
      19 colorectal complications, a prevalence of 0.3 percent for the initial hospital
      stay following bypass surgery. Mortality in those with complications was 37
      percent (7/19). Of the 19 complications, 9 (47 percent) followed coronary artery
      bypass grafting, whereas 10 (53 percent) followed valve replacement or combined
      coronary artery bypass grafting with other cardiac procedures. Five (26 percent)
      of the complications followed emergency cases, whereas 14 (74 percent) followed
      elective cases. Average age of those with complications was 69.8 years, compared
      with 63.2 years for those without complications. Average aortic cross-clamp time
      for those with complications was 71 +/- 25 minutes; pump time was 106 +/- 34
      minutes. That was significantly higher than in those without complications. Nine
      (47 percent) patients with complications required vasopressors during the
      perioperative period, whereas eight (42 percent) suffered prolonged hypotension
      (systolic blood pressure, < 90 mmHg). CONCLUSIONS: It appears that increased age,
      valve replacement, or combined cardiac procedures, emergency procedures, and
      prolonged aortic cross-clamp and bypass pump times are risk factors for
      development of colorectal complications. Hypoperfusion, as suggested by prolonged
      pump times, clamp times, and emergency procedures may be a possible cause for
      development of colorectal complications.

PMID- 7587768
TI  - Laparoscopic very low anterior resection and coloanal anastomosis using the pull
      through technique.

PMID- 7587767
TI  - New anastomotic gun for biofragmentable anastomotic ring in low anterior
      resection.
AB  - PURPOSE: The biofragmentable anastomotic ring remains difficult to use for low
      rectal anastomosis. The authors report their experience of clinical application
      of the biofragmentable ring in low anterior resection with a newly designed
      instrument. METHODS: In this series, 31 patients underwent sphincter-preserving
      low anterior resections for rectal tumors from May 1993 to November 1994. With
      the assistance of a self-developed anastomotic instrument (biofragmentable
      anastomotic ring gun), biofragmentable ring anastomoses were performed following
      low anterior resection. RESULTS: There was no operative mortality. One patient
      had clinical evidence of anastomotic leakage. In postoperative follow-up, there
      was no anastomotic stenosis or incontinence. CONCLUSION: Therefore, we believe
      biofragmentable ring rectal anastomosis is a safe and reliable alternative to
      other anastomotic methods in rectal surgery.

PMID- 7587769
TI  - Pyogenic liver abscess: warning indicator of silent colonic cancer. Report of a
      case and review of the literature.
AB  - PURPOSE: Carcinoma of the colon, manifested clinically as an enterococcal hepatic
      abscess, in the absence of liver metastases, is very uncommon. However, having
      treated a patient with such a condition, we would like to draw the attention of
      surgeons to this possibility. Most reports describe secondary infections of
      hepatic metastases only in patients with a known malignancy. However, increased
      awareness of colonic cancer as an underlying cause of pyogenic liver abscesses
      will afford earlier diagnosis and treatment. METHODS: The case was analyzed for
      history, presentation, laboratory data, radiologic studies, and bacteriology.
      RESULTS: A 66-year-old woman presented with abdominal pain, fever, and chills.
      Imaging scans revealed a solitary liver abscess, which was successfully treated
      with percutaneous drainage and broad-spectrum intravenous antibiotics. Pus
      cultures grew Streptococcus faecalis. A search for the underlying cause led to
      the discovery of an adenocarcinoma of the sigmoid colon. CONCLUSIONS: An
      aggressive search for the underlying cause of pyogenic liver abscesses should be
      an integral part of the definitive treatment of this disease. After prevailing
      etiologies have been excluded, silent colonic cancer should be considered.

PMID- 7587770
TI  - Ergotamine-induced complex rectovaginal fistula. Report of a case.
AB  - PURPOSE: This report stresses the importance of local complications caused by
      ergotamine abuse for the treatment of migraine headaches. METHODS: We present an
      unusual case of a complex rectovaginal fistula (RVF) caused by long-term
      ergotamine suppository abuse. RESULTS: A 39-year-old female was referred after
      she had undergone a transverse colostomy for temporary fecal diversion.
      Evaluation, including proctoscopy, gastrograffin enema, vaginogram, and pelvic
      computerized tomography revealed a RVF 6 cm proximal to the dentate line with
      distal rectal stricture. Surgical intervention included take down of the
      transverse colostomy with reanastomosis, proctectomy with excision of the
      fistula, creation of a colonic "J-pouch" with a coloanal anastomosis, and
      construction of a temporary loop ileostomy. The patient had an uneventful
      recovery, and her ileostomy was closed three months later. Pathologic examination
      of the surgical specimen failed to reveal any specific etiology of the RVF.
      However, her ten-year use of up to five ergotamine suppositories per day for
      migraine treatment is associated with a local ischemic effect. Pathophysiology of
      this rare cause of RVF and the surgical procedure are discussed. CONCLUSION: If
      evidence of any side effects of ergotamine suppositories is seen, early
      discontinuation of the drug should be considered to avoid complications such as
      RVF and/or strictures.

PMID- 7587771
TI  - Colorectal cancers of rare histologic types compared with adenocarcinomas.

PMID- 7587772
TI  - First-pass metabolism of alcohol. Absence of diurnal variation and its inhibition
      by cimetidine after evening meal.
AB  - To determine whether the first-pass metabolism (FPM) of orally consumed alcohol
      varies with the time of day, 12 healthy male subjects were tested with both oral
      and intravenous alcohol (0.3 g/kg), in the morning and evening, always 1 hr after
      the same standard meal. The results revealed no significant differences in FPM
      (81.6 +/- 11.6 vs 92.8 +/- 10.6 mg/kg) or in any other index of alcohol
      absorption and metabolism. Eleven subjects were also tested in the evening after
      treatment with cimetidine, an H2-antagonist that inhibits gastric alcohol
      dehydrogenase activity in vitro. Compared to baseline, cimetidine (1 g/day for
      eight days) significantly decreased FPM (from 100.1 +/- 8.0 to 52.6 +/- 11.4
      mg/kg, P < 0.01) and increased the systemic bioavailability of alcohol (from 66
      +/- 3 to 82 +/- 4%, P < 0.01), as well as peak blood alcohol concentrations (from
      4.3 +/- 0.4 to 5.9 +/- 0.5 mM, P < 0.05) and areas under the curve (from 5.1 +/-
      0.5 to 7.0 +/- 0.5 mM/hr, P < 0.01). The results indicate the absence of diurnal
      variation in FPM and suggest that patients given cimetidine should be warned of
      its possible interaction with alcohol regardless of the time of day.

PMID- 7587773
TI  - Significance of human leukocyte antigens DR3 and DR4 in chronic viral hepatitis.
AB  - Immune mechanisms have been implicated in chronic viral hepatitis, and these may
      be influenced by genetic factors. To determine if disease severity in chronic
      viral hepatitis is associated with the human leukocyte antigens DR3 and/or DR4,
      109 patients were evaluated prospectively. The frequencies of DR3 and DR4 in
      these patients were compared to those in 80 normal subjects. Patients with DR3
      and/or DR4 had the same occurrence of severe disease as patients with other DR
      antigens (21% versus 30%, P = 0.3). Patients with DR3, however, had higher serum
      gamma globulin and immunoglobulin G levels than patients with DR4 and a greater
      frequency of severe disease (36% vs 12%, P = 0.046). Patients with DR4 had
      concurrent immunologic diseases more commonly than patients with DR3 (44% vs 9%,
      P = 0.005) and patients with other DR antigens (44% vs 9%, P = 0.0002). Patients
      with DR4 but not DR3 had severe disease less frequently than other patients (9%
      vs 31%, P = 0.02). The frequencies of DR3 in patients with severe disease (37% vs
      18%, P = 0.06) and DR4 in patients without severe disease (44% vs 30%, P = 0.07)
      were different than those in normal subjects but not to a statistically
      significant level. We conclude that patients with DR3 and DR4 have different
      clinical and laboratory findings and disease severity. Patients with DR4 have
      milder disease than patients with other DR antigens. Disease severity, however,
      is not closely associated with DR3 or DR4.

PMID- 7587775
TI  - Primary biliary cirrhosis induced by interferon-alpha therapy for hepatitis C
      virus infection.
AB  - Interferon-alpha is known to exacerbate and in some cases induce a variety of
      autoimmune disorders. In this report we describe the onset of primary biliary
      cirrhosis in a 55-year-old woman without evidence of preexisting autoimmune
      diseases receiving recombinant interferon-alpha 2a for chronic active hepatitis
      C. Shortly after discontinuing interferon therapy, alkaline phosphatase levels
      started to rise up to three times the normal range. Anti-mitochondrial antibodies
      were found to be positive at a high titer, and liver biopsy showed a picture of
      chronic active hepatitis along with primary biliary cirrhosis features (overlap
      syndrome). Primary biliary cirrhosis should be considered in the differential
      diagnosis in any patient treated with interferon-alpha with unexplained elevation
      of serum alkaline phosphatase.

PMID- 7587774
TI  - Serum levels of interferon-alpha and -gamma in acute and chronic hepatitis B
      virus infection.
AB  - To evaluate the potential implication of in vivo interferon production in the
      pathogenesis of different forms of acute and chronic hepatitis B virus infection,
      serum levels of interferon-alpha and -gamma were measured using immunoassay
      techniques in 20 patients with acute hepatitis B who subsequently cleared the
      virus (group Ia), 8 patients with acute hepatitis B who became HBsAg carriers
      (group Ib), 55 patients with chronic hepatitis B (group II), and 15 healthy
      controls. None of the controls had interferon-alpha or -gamma detectable in
      serum, while 15% and 100% of group Ia patients, 25% and 100% of group Ib
      patients, and 22% and 15% of group II patients, had raised serum levels of
      interferon-alpha and -gamma, respectively. Serum interferon-gamma was detected
      significantly more frequently in group Ia and Ib patients than in controls and in
      group II patients. Among patients with acute hepatitis B, serum levels of
      interferon-alpha and -gamma showed no significant difference between group Ia and
      group Ib patients. Among patients with chronic hepatitis B, interferon-alpha was
      detected significantly more frequently in patients with serum HBV-DNA (31.4% or
      11/35) than in those without (5% or 1/20), whereas interferon-gamma was detected
      significantly more frequently in patients with chronic active hepatitis (28% or
      7/25) than in those with chronic persistent hepatitis (3.3% or 1/30). In
      conclusion, in acute hepatitis B, serum levels of interferon-alpha and -gamma did
      not show a significant difference between patients who subsequently cleared the
      virus and those who became HBsAg carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587777
TI  - Tuberculous peritonitis complicating corticosteroid therapy for acute alcoholic
      hepatitis.

PMID- 7587776
TI  - Development of granulomatous hepatitis during treatment with interferon-alpha 2b.

PMID- 7587779
TI  - Cholangiographic features in fibrosis and cirrhosis of the liver. Radiological
      pathological correlation.
AB  - The cholangiographic features of intrahepatic bile ducts associated with
      cirrhosis or fibrosis are not well known. In order to achieve a radiological
      pathological correlation, we studied nine livers with fibrosis or cirrhosis
      excised at autopsy. Cholangiograms were obtained within 24 hr after death from
      the nonfixed liver and multiple tissues samples were taken for histologic
      examination. Radiological data were interpreted by two independent investigators
      blinded to the clinical and histological findings. Cirrhosis (alcoholic in 4,
      posthepatitis in two) was observed in six livers, fibrosis (alcoholic in 2,
      posthepatitis in one) in three. No liver with fibrosis had cholangiographic
      abnormalities. In contrast, cholangiography of all livers with cirrhosis was
      abnormal. Abnormalities were a diminished arborization, a decrease of the distal
      opacification, an irregularity of caliber, and a tortuous course of the bile
      ducts. Histological study showed that the irregular and tortuous course were due
      to compression of the bile ducts by regenerative nodules. Furthermore, a thick
      fibrosis was organized around the bile ducts. In conclusion, fibrosis alone was
      not associated with cholangiographic abnormalities. In cirrhotic livers,
      intrahepatic bile ducts showed an irregular and tortuous course, a diminished
      arborization and a decrease of the distal opacification. These abnormalities were
      secondary to the presence of regenerative nodules and fibrosis organized around
      the bile ducts.

PMID- 7587778
TI  - Effects of transjugular intrahepatic portasystemic shunt (TIPS) on splanchnic and
      systemic hemodynamics, and hepatic function in patients with portal hypertension.
      Preliminary results.
AB  - The purpose of this study was to evaluate the short-term splanchnic and systemic
      hemodynamics and hepatic function after TIPS creation. Fifteen cirrhotics with
      portal hypertension underwent TIPS placement for treatment of variceal
      hemorrhage, and extensive hemodynamic studies including right heart
      catheterization, portal pressure measurement, hepatic blood flow, and indocyanine
      green (ICG) clearance were performed before and 1 month after the procedure. Self
      expandable metal stents (Strecker 11 mm diameter) were placed in all cases.
      Portasystemic gradient significantly diminished (18.3 +/- 4.2 vs 8 +/- 2.8; 54%
      +/- 18 mm Hg) after the technique, mainly due to a decrease in portal pressure,
      and remained stable in the final study. Cardiac output and mean arterial pressure
      increased (6.2 +/- 1.4 vs 8.2 +/- 1.8 liters/min, 80.1 +/- 10.1 vs 91 +/- 11.2 mm
      Hg, respectively), and a decrease in systemic vascular resistance was registered
      (1018 +/- 211 vs 872 +/- 168 dyne/sec/cm5); the hepatic blood flow and ICG
      clearance also decreased significantly (1.5 +/- 0.7 vs 0.68 +/- 0.2 liters/min,
      0.4 +/- 0.2 vs 0.24 +/- 0.06 liters/min, respectively). There was an increase in
      the preload at the final study, as evidenced by a marked increase in right atrial
      (3.1 +/- 1.6 vs 4.35 +/- 2.2 mmHg, +15%, P < 0.05), pulmonary arterial (12.2 +/-
      2.4 vs 15.9 +/- 3.2 mm Hg, +31.8%, P < 0.001), and wedge pulmonary arterial
      pressures (6.9 +/- 2.4 vs 9.8 +/- 3.1 mm Hg, +53%, P < 0.001). These results
      suggest that TIPS worsens the hyperdynamic syndrome associated to portal
      hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587781
TI  - Structure and composition of primary intrahepatic stones in Korean patients.
AB  - We have analyzed the chemical composition of primary intrahepatic stones from 72
      Korean patients. Two types of concretions have been identified: brown pigment
      (calcium bilirubinate) stones and black-colored mixed stones. Brown pigment
      stones were found in 68% of all cases and the remainder (32%) consisted of mixed
      stones. Intrahepatic mixed stones had mean cholesterol and bilirubin contents of
      46.6% and 25.9%, respectively, whereas calcium bilirubinate stones had mean
      cholesterol and bilirubin contents of 14.1% and 43.6%, respectively. Intrahepatic
      mixed stones had a smooth black-colored surface and on cross section, exhibited a
      distinct outer shell surrounding an inner yellow, cholesterol-rich body. The
      finding of intrahepatic mixed stones with high cholesterol content suggests that
      primary hepatolithiasis may result from at least two different conditions or
      disorders and points to different approaches to their treatment.

PMID- 7587784
TI  - Intestinal morphology and cytokinetics in pancreatic insufficiency. An
      experimental study in the rat.
AB  - Intraluminal pancreatic enzymes influence intestinal function, adaptation, and
      susceptibility to injury. These effects may be mediated partly through changes in
      the rate of epithelial cell turnover. We assessed intestinal morphology and
      cytokinetics in a rat model of exocrine pancreatic insufficiency that does not
      alter anatomic relationships or animal growth. Pancreatic duct occlusion was
      performed by applying metal clips on both sides along the common bile duct.
      Control animals underwent sham-operation with exposure and manipulation of the
      pancreas without duct occlusion. Twelve days later, pulse labeling with tritiated
      thymidine was performed, and mitotic arrest was induced with colcemid. Groups of
      animals were sacrificed at 0 and 2 hr after colcemid injection. Specimens for
      histopathology, morphometry, and autoradiography were obtained from duodenum,
      proximal jejunum, distal jejunum, and ileum. Labeling index, grain counts,
      mitoses per crypt, cells per crypt, cells per villus, crypt depth, villus height,
      and number of goblet cells per villus were used as end points. Pancreatic duct
      occlusion resulted in increased labeling index across intestinal segments
      relative to sham-operated controls (P < 0.01) and increased labeling index and
      mitotic rate in distal compared to proximal intestine (P < 0.05). Grain-count
      histograms were similar in the two experimental groups. There were no significant
      morphologic differences between pancreatic duct-occluded animals and controls.
      Exocrine pancreatic insufficiency increases crypt cell proliferation in distal
      small intestine but does not alter the duration of S phase. These changes are
      most likely due to an increase in the size of the proliferative compartment and
      may be partly responsible for changes in small bowel function and response to
      injury.

PMID- 7587780
TI  - Differential distribution of human epidermal growth factor receptor family in
      acute pancreatitis.
AB  - Using northern blot analysis and immunohistochemistry, we assessed the expression
      and distribution of human epidermal growth factor receptor-1 (HER-1), HER-2, and
      HER-3 in pancreatic tissues obtained from patients with acute pancreatitis (AP).
      Overall, HER-1, HER-2, and HER-3 mRNA levels were similar in the normal pancreas
      and in the pancreas of AP patients. However, three patients exhibited a
      significant increase in HER-1 mRNA levels. Furthermore, the distribution of the
      receptors differed with respect to the various cell types in the human pancreas.
      In the normal pancreas, moderate HER-1 and strong HER-3 immunoreactivity was
      present predominantly in the cytoplasm of acinar cells and to a lesser extent in
      the ductal cells, whereas strong HER-2 immunoreactivity was present in the islet
      cells. In the AP tissues, there was a marked increase in HER-1 immunoreactivity
      in acinar and ductal-like cells, whereas HER-3 immunoreactivity was less
      prominent in acini and increased in ductal-like cells. HER-2 immunoreactivity was
      again mainly evident in islet cells, but was also present in the ductal-like
      cells. These findings indicate that there is altered distribution of HERs in the
      pancreas following AP and raise the possibility that HERs may be involved in the
      process of pancreatic regeneration during recovery from AP.

PMID- 7587782
TI  - Cholecystokinin-8 induces edematous pancreatitis in dogs associated with short
      burst of trypsinogen activation.
AB  - To study the early pathogenesis of acute edematous pancreatitis in dogs, we
      examined the relationship of pancreatic hyperstimulation with cholecystokinin-8
      (10 micrograms/kg/hr intravenously for 6 hr) to alterations in circulating
      pancreatic enzymes and pancreatic morphology with special reference to
      trypsinogen activation. Cholecystokinin-8 infusion was associated with increases
      in plasma amylase, lipase, trypsin-like immunoreactivity, and plasma and urine
      trypsinogen activation peptide. Pancreatic parenchymal swelling and interlobular
      and subcapsular fluid accumulations were detected ultrasonographically within 2
      hr of cholecystokinin-8. Circulating trypsin-like immunoreactivity and
      trypsinogen activation peptide in urine reached a peak at 2 and 4 hr,
      respectively, then declined despite progressive increases in circulating amylase
      and lipase and intrapancreatic fluid. No significant changes were observed in
      dogs receiving a saline infusion. This study illustrates that cholecystokinin-8
      induces edematous pancreatitis in dogs that is associated with a short-lived
      burst of trypsinogen activation.

PMID- 7587785
TI  - Neutrophil elastase inhibitor (ONO-5046) prevents lung hemorrhage induced by
      lipopolysaccharide in rat model of cerulein pancreatitis.
AB  - The protective effects of a neutrophil elastase inhibitor (ONO-5046) on cerulein
      induced pancreatitis followed by a septic challenge with intraperitoneal
      lipopolysaccharide (LPS) were studied in a rat model. Pancreatitis was induced by
      four intramuscular injections of cerulein (50 micrograms/kg at 1-hr intervals).
      ONO-5046 was administered by continuous intravenous infusion via the right
      jugular vein (50 mg/kg/hr, 30 min prior to the first cerulein injection to 20 hr
      following the last cerulein injection). Significant differences in serum amylase
      and pancreatic wet weight ratio were not observed between the animals with
      pancreatitis treated with or without ONO-5046. There was no significant
      difference in the in vitro tumor necrosis factor-alpha (TNF-alpha) production by
      peritoneal macrophages from rats with pancreatitis treated with or without ONO
      5046. In a second experiment, LPS (10 mg/kg) was administered intraperitoneally
      as the septic challenge 6 hr following the first cerulein injection. Lung
      hemorrhage was seen in the animals with pancreatitis untreated with ONO-5046 24
      hr following the first cerulein injection. No significant lung hemorrhage was
      observed in the animals with pancreatitis treated with ONO-5046 administering 30
      min prior to the first cerulein injection. These results suggest that lung
      hemorrhage in cerulein-induced pancreatitis that follows a septic challenge with
      LPS can be prevented by the intravenous administration of ONO-5046. Thus there is
      a significant role for neutrophil elastase in pancreatitis-associated lung
      injury.

PMID- 7587783
TI  - Protective effect of nitric oxide on development of acute pancreatitis in rats.
AB  - Nitric oxide (NO) has been implicated to regulate pancreatic circulation, promote
      capillary integrity, and inhibit leukocyte adhesion. We investigated the role of
      NO in the development of pancreatitis. Nitro-L-arginine, an inhibitor of NO
      synthase, in total dose of 35 mg/kg body wt was infused in the rats with
      edematous pancreatitis induced by two intraperitoneal injections of cerulein (20
      micrograms/kg). L-Arginine (125 or 250 mg/kg), a NO donor was intravenously
      administered twice in the rats with hemorrhagic pancreatitis induced by water
      immersion stress plus two intraperitoneal injections of cerulein (40
      micrograms/kg). The degree of pancreas edema, serum amylase levels, and
      histologic alterations were investigated. Nitro-L-arginine exacerbated cerulein
      induced pancreatitis and caused a decrease in pancreatic blood flow. L-Arginine
      ameliorated the severity of hemorrhagic pancreatitis dose dependently and
      improved the pancreatic blood flow. These findings suggest that NO could confer
      protection against the development of hemorrhagic pancreatitis, probably through
      improvement of the pancreatic microcirculation.

PMID- 7587786
TI  - Effect of microcirculatory perfusion on distribution of trypsinogen activation
      peptides in acute experimental pancreatitis.
AB  - Extraintestinal trypsinogen activation peptides (TAP) have been shown to
      correlate with severity of acute pancreatitis in humans as well as in various
      animal models. Ischemia superimposed on experimental pancreatitis, however,
      increases acinar cell injury without increasing TAP in plasma. We speculated that
      TAP generated in the pancreas might not reach the circulation in necrotizing
      pancreatitis due to decreased pancreatic perfusion. To test the hypothesis that
      generation of TAP in plasma is related to pancreatic perfusion and that plasma
      TAP may therefore underestimate acinar cell injury in necrotizing disease, we
      correlated TAP in pancreatic tissue and body fluids with capillary pancreatic
      blood flow in necrotizing and edematous pancreatitis. The ratio between necrosis
      and TAP in tissue was similar in both models; the ratio between TAP in plasma and
      tissue, however, was significantly lower in necrotizing pancreatitis, indicating
      that a certain amount of TAP generated in the pancreas did not reach the
      circulation. Decreased pancreatic perfusion found in necrotizing pancreatitis was
      consistent with this finding. Our data suggest that TAP in tissue is most
      reliable to indicate severity of acute pancreatitis, whereas plasma TAP may
      underestimate pancreatic injury in necrotizing disease due to decreased
      pancreatic perfusion.

PMID- 7587787
TI  - Classification of gallstones and epidemiologic studies.

PMID- 7587788
TI  - Localization of an obstructing esophageal lesion. Is the patient accurate?
AB  - There are many options as to the accuracy of a patient's subjective localization
      of an obstructing esophageal lesion. However, there are few studies specifically
      examining this issue. Over a 35-month period, all patients evaluated by our
      gastroenterology service undergoing endoscopy for dysphagia were prospectively
      identified. The patient's subjective localization for the level of obstruction
      was evaluated by an investigator blinded to the results of prior barium
      esophagography and recorded on a schematic of the bony skeleton. At the time of
      endoscopy, the most proximal level of the obstructing lesion was documented. In
      all, 139 patients with dysphagia and an esophageal stricture were evaluated.
      Barium esophagograms were performed prior to endoscopy in all but nine patients
      (6.5%). The most common lesions causing dysphagia were carcinoma (34.5%),
      gastroesophageal reflux disease (22.3%), and a Schatzki's ring (15.8%). The level
      of obstruction was localized exactly in 30 patients (21.6%), within +/- 2 cm in
      72 (52%), and within +/- 4 cm in 31 additional patients (74%). Eight patients
      (15%) with a distal esophageal lesion localized the obstruction to the proximal
      esophagus, whereas only two patients (5%) with a lesion in the proximal esophagus
      localized the level of obstruction to the distal esophagus. Overall, patients
      with distal obstructing lesions were more likely to have referral > 6 cm
      proximally than proximal lesions with referral to the distal esophagus (P =
      0.003). There were no significant differences in accuracy based on the cause of
      dysphagia. In conclusion, a patient's subjective localization of the level of an
      esophageal stricture is highly accurate. Patients appear to be most accurate in
      localizing proximal rather than distal lesions.

PMID- 7587789
TI  - Esophageal tissue band transected with hot biopsy forceps.

PMID- 7587790
TI  - Influence of cisapride on gastric emptying of solids and liquids monitored by 13C
      breath tests.
AB  - [13C]Acetate and [13C]octanoate breath tests were used to analyze the gastric
      emptying of liquids and solids in healthy controls and patients with functional
      dyspepsia both with and without cisapride. A standard test meal was labeled with
      either 150 mg [13C]acetate (liquid phase labeled in the water) or with 100 mg
      [13C]octanoate (solid phase labeled in the egg yolk). Six patients with dyspepsia
      and six healthy controls underwent a 4-hr breath test four times, ie, both the
      [13C]acetate and [13C]octanoate test with and without cisapride. Duplicate
      [13C]acetate or [13C]octanoate breath tests were performed in another 12 healthy
      controls in order to assess day-to-day variability of gastric emptying for
      liquids and solids. The mass spectrometric data were fitted to a power
      exponential function allowing mathematical analysis of half-emptying times and
      lag times. In patients with dyspepsia, gastric half emptying times of solids were
      significantly delayed as compared to the emptying of solids in the controls (203
      +/- 41 vs 148 +/- 35 min; P < 0.05). With cisapride, gastric emptying of solids
      was significantly accelerated (P < 0.05) both in the patients (166 +/- 58 min)
      and in the controls (117 +/- 27 min). The gastric emptying of liquids did not
      differ in patients and controls, and cisapride had no effect on the emptying of
      liquids within the normal range. In the healthy controls, half emptying times
      both for liquids and solids were reproducible on the two different days (CVintra:
      5.58% for liquids, 20.01% for solids).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587791
TI  - Gastric mucosal histamine storing cells. Evidence for different roles of mast
      cells and enterochromaffin-like cells in humans.
AB  - Gastric mucosal histamine content, enterochromaffin-like cell density, and mast
      cell density were studied in 13 subjects under omeprazole therapy, 13 partially
      gastrectomized subjects with a Billroth II reconstruction, 10 partially
      gastrectomized subjects with a Roux-en-Y reconstruction, and 9 control subjects.
      Histamine content was significantly greater both in the subjects with higher
      gastrinemic levels (omeprazole-treated subjects) and those with more abundant
      enterogastric reflux (Billroth II subjects) than in controls. Enterochromaffin
      like cell density was significantly greater in the omeprazole subjects than in
      each of the other groups. Mast cell density was significantly greater in Billroth
      II subjects than in controls. Serum gastrin levels, mucosal histamine content,
      and enterochromaffin-like cell density were positively correlated. Gastrin was
      not correlated to mast cell density. These results support the existence of
      different control pathways for enterochromaffin-like and mast cells. Moreover,
      they suggest that enterochromaffin-like cells and mast cells are involved in the
      regulation of gastric secretion and in gastric mucosal injury-repair mechanisms,
      respectively, due to histamine release.

PMID- 7587792
TI  - Detection and partial sequence analysis of Helicobacter pylori DNA in the bile
      samples.
AB  - The existence of Helicobacter pylori in the biliary tract was investigated. Seven
      bile samples were included in this study. Among them, six bile samples were
      collected by percutaneous transhepatic cholangiodrainage and the other by needle
      aspiration during cholecystectomy. Using nested PCR with two sets of primers
      homologous to the urease A gene, Helicobacter pylori DNA was detected. Three
      samples, one from a patient with advanced gastric cancer involving the pancreatic
      head and two from patients with pancreatic head tumor, were found to be positive
      for Helicobacter pylori DNA. On the other hand, three samples from patients with
      cholangiocarcinoma and one from a patient with chronic cholecystitis were all
      negative. To further verify the specificity of our PCR analysis, partial
      sequences of the PCR products from the three positive samples were analyzed by
      direct sequencing. Several silent mutations and a missense mutation (AAA to AGA;
      Lys-164 to Arg-164) were identified in the urease A gene. We conclude that
      Helicobacter pylori DNA can be easily detected in the bile samples. The
      possibility of asymptomatic cholangitis caused by this organism requires further
      investigation.

PMID- 7587793
TI  - Effect of NSAIDs on gallbladder bile composition.
AB  - Secretion of gallbladder mucin is an important step in gallstone pathogenesis.
      Previous studies have demonstrated that aspirin and other nonsteroidal
      antiinflammatory drugs (NSAIDs) can both inhibit gallbladder mucin secretion and
      prevent gallstone formation in animal models of cholesterol gallstone disease.
      The present study was performed to determine if chronic NSAID use was associated
      with a reduction in the mucin content or affected the lipid components of human
      gallbladder bile. Four groups of patients were identified retrospectively from a
      cohort of 230 morbidly obese patients who underwent gastric bypass surgery. The
      index group consisted of 18 patients who were found to have gallstones at gastric
      bypass surgery and had a history of chronic NSAID use. Three other patient groups
      were identified from the cohort by matching this index population for sex, race,
      and age according to the following criteria: (1) patients with gallstones who had
      not utilized NSAIDs, (2) patients without gallstones but with chronic NSAID use,
      and (3) patients without gallstones and without a history of NSAID use.
      Gallbladder bile was obtained from all patients by direct aspiration from the
      gallbladder at the time of surgery. Patients with gallstones had a significantly
      (P < 0.02) greater concentration of gallbladder mucin in their gallbladder bile
      compared to patients without gallstones (0.897 +/- 0.226 vs 0.173 +/- 0.039
      mg/ml). Among gallstone patients, gallbladder mucin was reduced in those patients
      with a history of chronic NSAID use (1.18 +/- 0.43 vs 0.74 +/- 0.19
      mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587795
TI  - Intraoperative enteroscopy in the diagnosis of partial intestinal obstruction in
      infancy.
AB  - We present the case of a 4-month-old infant with a prolonged illness due to an
      occult intestinal stricture. Diagnosis of the lesion escaped conventional
      radiologic and surgical methods and required intraoperative enteroscopy.
      Resection of the stricture lead to prompt clinical improvement. Our patient
      illustrates a primary diagnostic use of intraoperative enteroscopy in the
      detection of a partial intraluminal small bowel obstruction. As further
      experience accumulates with small bowel endoscopy, roles for therapeutic
      enteroscopy (such as polypectomy, photocoagulation, and perhaps balloon
      dilatation) will certainly arise. Such endeavors will depend on the continued
      productive collaboration between members of the surgical and gastroenterological
      teams.

PMID- 7587797
TI  - Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of
      irritable bowel syndrome. A multicenter dose-response study.
AB  - The efficacy and safety of the peripheral kappa agonist fedotozine was evaluated
      in a double-blind, multicenter study involving 238 patients with the irritable
      bowel syndrome. After a two-week washout, patients were assigned to one of four
      groups to receive either placebo or fedotozine three times a day at doses of 3.5,
      15, or 30 mg for six weeks. Patient assessment of mean symptom intensity
      indicated that the 30-mg dose of fedotozine was superior to placebo in relieving
      maximal daily abdominal pain (P = 0.01), mean daily pain (P = 0.007), and
      abdominal bloating (P = 0.02). Changes in bowel function and defecation disorders
      could not be evaluated reliably. According to the investigators, the highest dose
      of fedotozine markedly reduced overall disease severity (P = 0.003) and the pain
      component of the symptomatic profile (P = 0.009). Clinical and laboratory safety
      was very good. Fedotozine 30 mg three times a day therefore appears to be
      effective and safe in the treatment of the abdominal pain and bloating associated
      with IBS.

PMID- 7587798
TI  - Changes in substance P-immunoreactive innervation of human colon associated with
      ulcerative colitis.
AB  - The amount of colonic substance P and substance P-receptors is increased in
      ulcerative colitis, which may denote that substance-P is involved as a neurogenic
      mediator in the inflammatory process of ulcerative colitis. We studied the
      anatomical distribution of elevated colonic substance P in ulcerative colitis and
      assessed morphometrically whether the changes in substance P correlate with
      alterations in colonic innervation. Full-thickness specimens of colonic wall were
      obtained from normal human colons (N = 9) and the most and least affected regions
      of ulcerative colitis colons (N = 10) and immunostained for substance P.
      Substance P immunoreactivity index was calculated by multiplying each intensity
      value by the number of pixels exhibiting this intensity value. The numbers of
      substance P-immunoreactive nerve fibers in the lamina propria were markedly
      increased, and their fluorescence intensity was enhanced in ulcerative colitis.
      The longitudinal muscle layer contained substance P-immunoreactive nerve fibers
      in ulcerative colitis, but not in the controls. The substance P-immunoreactive
      index (= number x intensity of nerve fibers) was 3.42 +/- 1.49 in controls, 21.19
      +/- 7.79 in mild ulcerative colitis regions (P < 0.05), and 29.68 +/- 9.81 in
      severe ulcerative colitis regions (P < 0.01). Increase in the number of substance
      P nerve fibers is in accordance with the hypothesis that substance P contributes
      to neurogenic mediation of inflammation in ulcerative colitis.

PMID- 7587796
TI  - Absence of effect of nicotine on rectal sensation, rectal compliance, and anal
      sphincter pressures in healthy subjects.
AB  - We examined the effect of nicotine on rectal sensation, rectal compliance, and
      anorectal sphincter function in healthy volunteers. Eleven healthy (ex-smoker)
      subjects were randomized in a double-blind, crossover, placebo-controlled study
      of 12 mg nicotine-containing chewing gum. All treatment periods (nicotine or
      placebo chewing gum) were preceded by a control period without chewing gum.
      Crossover study was done after a washout period of more than seven days. The
      following measurements were made: highest anorectal sphincter tone, highest
      anorectal sphincter squeeze tone, percentage relaxation of the anorectal
      sphincter with rectal balloon distension, threshold of rectal sensation, maximal
      tolerable volume of air inflation of a rectal balloon, and rectal compliance.
      There was no significant difference in the two control periods. Chewing placebo
      gum had no significant effect on any of the measurements when compared with
      control. Compared with placebo, nicotine did not significantly affect on any of
      the measurements. We conclude that neither nicotine nor the sham-feeding effect
      of chewing placebo gum appear to have any effect on anorectal sensorimotor
      function or on rectal compliance in healthy ex-smokers.

PMID- 7587794
TI  - Isoproterenol-induced gastric mucosal protection from bile acid. Role of
      endogenous prostaglandins.
AB  - Topical isoproterenol is a potent protective agent against bile acid-induced
      gastric mucosal injury in hypotensive and normotensive rats. This study was
      undertaken to ascertain what role endogenous prostaglandins and gastric mucosal
      blood flow play in isoproterenol-induced protection. Accordingly, anesthetized,
      fasted rats were given the cyclooxygenase inhibitor, indomethacin (5 mg/kg
      subcutaneously), 30 min prior to topical pretreatment with 3 ml of intragastric
      saline, isoproterenol (3 microM), or 16,16-dimethyl prostaglandin E2 (3 microM)
      for 15 min. Gastric injury was induced with topical 5 mM acidified taurocholate
      and damage assessed by measuring net transmucosal ion fluxes, the appearance of
      DNA into the gastric lumen, and histology of the gastric epithelium. In a
      separate set of experiments, the effects of topical isoproterenol on gastric
      mucosal blood flow (laser Doppler flowmetry) and luminal PGE2 concentrations
      (125I radioimmunoassay) were examined. Pretreatment with topical isoproterenol or
      16,16-dimethyl prostaglandin E2 significantly decreased bile acid-induced net
      luminal ion fluxes and DNA accumulation, suggesting mucosal protection. The
      protective effect of isoproterenol, but not 16,16-dimethyl prostaglandin E2, was
      negated by indomethacin (corroborated by histology). Further, isoproterenol did
      not significantly alter gastric mucosal blood flow, but did augment luminal PGE2
      concentrations, an effect also abolished by indomethacin. Thus, isoproterenol
      appears to protect the gastric mucosa from the damaging effects of bile acid
      through a mechanism that requires the synthesis and release of cytoprotective
      endogenous prostaglandins.

PMID- 7587799
TI  - D-xylose hydrogen breath tests compared to absorption kinetics in human patients
      with and without malabsorption.
AB  - The D-xylose breath H2 test may be useful in characterizing intestinal absorptive
      function. Our aim was to determine whether breath H2 following D-xylose
      administration reflects the extent to which the D-xylose is absorbed by comparing
      it to a kinetic model of D-xylose absorption. Twenty-five subjects were studied.
      They ingested 15 g D-xylose on the first day and 25 g D-xylose on the third day.
      On the second day they received 10 g intravenous D-xylose along with 15 g oral
      lactulose. Multiple serum and urine samples were obtained for D-xylose content to
      calculate its rate constants and extent of absorption by multicompartmental
      analysis. Breath H2 determinations were obtained every 15 min for 3 hr following
      the 15 g D-xylose and lactulose ingestion. Peak breath H2 concentration
      correlated with extent of absorption (r = -0.787, P < 0.001), K0, the rate
      constant for nonabsorptive loss (r = 0.744, P < 0.001), and 5-hr urine content (r
      = -0.705, P < 0.001). Area under the breath H2 curve also correlated with these
      parameters: extent of absorption (r = -0.770, P < 0.001), K0 (r = 0.662, P <
      0.001), 5-hr urine content (r = -0.629, P < 0.012). Peak D-xylose breath H2 to
      peak lactulose breath H2 showed no correlation with extent of absorption. The
      extent of absorption was higher with the 15-g dose than the 25-g dose in all
      patients tested (P < 0.01). (ABSTRACT TRANCATED AT 250 WORDS)

PMID- 7587800
TI  - Phorbol myristate acetate ex vivo model of enhanced colonic epithelial
      permeability. Reactive oxygen metabolite and protease independence.
AB  - The initiating mechanisms involved in colonic injury are currently unknown. The
      goal of the current study was to examine the role of the inflammatory mediators
      reactive oxygen metabolites and proteases in an ex vivo model of selective
      epithelial permeability. Rats were prepared with exteriorized colonic chambers to
      which the protein kinase C (PKC) activator phorbol myristate acetate (PMA) was
      added in doses ranging from 5 to 800 micrograms. PMA caused a dose-dependent
      transient increase in epithelial permeability, but had no significant effect on
      microvascular permeability. There was no accumulation of neutrophils and no
      apparent histological changes. PMA acts via a PKC-dependent mechanism, as
      assessed using the PKC-inactive phorbol analog 4 alpha-phorbol didecanoate, and
      the response is tachyphylactic. The mechanism is independent of reactive oxygen
      metabolites and proteases, as shown by the lack of effect of the free radical
      scavengers superoxide dismutase and catalase and the general serine protease
      inhibitor soybean trypsin inhibitor. The classic inflammatory process does not
      appear to be involved in the PMA-induced epithelial permeability changes. This
      finding suggests that noninflammatory mechanisms may regulate the increased
      epithelial permeability induced by PMA. Further study to elucidate these
      mechanisms is of importance for understanding both normal gastrointestinal
      physiology and initiation of pathology.

PMID- 7587801
TI  - Production of activin A in human intestinal epithelial cell line.
AB  - Production of activin was studied in four cell lines of epithelial cells: FRTL-5,
      JCT-12, GH4C1, and FHs74Int cells. Bioactivity of activin was detected in
      conditioned media of FRTL-5, JCT-12, and FHs74Int cells. Among these three cell
      lines, FHs74Int cells, which were derived from human embryonic intestine,
      released a relatively f1p4e amount of bioactive activin. In these cells, serum
      and epidermal growth factor (EGF), which were capable of stimulating DNA
      synthesis, augmented release of bioactive activin in middle to late G1 phase. In
      addition, basic FGF (bFGF), which had no effect on DNA synthesis in these cells,
      also increased release of activin. In bFGF-treated FHs74Int cells, bioactive
      activin was released within 4 hr of the addition of bFGF. The reverse
      transcription polymerase chain reaction reveals that mRNA for only the beta A
      subunit of activin is expressed in these cells. Immunoblotting of lysate from
      serum-treated cells using anti-human activin A antibody indicated the existence
      of a 12.5-kDa protein under a reducing condition. FHs74Int cells did not express
      binding site for [125I]activin A and exogenous activin A did not affect DNA
      synthesis in these cells. These results indicate that FHs74Int cells derived from
      human embryonic intestine synthesize and release activin A. Activin A released
      from intestinal epithelial cells might be a modulatory factor in cells in
      intestinal mucosa.

PMID- 7587803
TI  - Anal "epistaxis": exteriorization of rectal bleeding during colonoscopy.

PMID- 7587804
TI  - Gastroprotection by dairy foods against stress-induced ulcerogenesis in rats.
AB  - We investigated the ability of three dairy foods to prevent stress-induced
      gastric lesions and bleeding in rats. Skim milk, whole milk, and cream were all
      significantly gastroprotective with the greatest protection seen with the highest
      fat dairy food. Pretreatment of rats with cream for up to 2 hr prior to stress
      maintained a portion of the protective effect. Lipid extracts of cream, but not
      skim milk or whole milk, were gastroprotective. Surface hydrophobicity of the
      gastric mucosa was reduced by stress, but was maintained at prestress levels by
      treatment with milk, cream, or their lipid extracts, although this effect was not
      sufficient for protection in stressed rats. Alterations in gastric pH or
      titratable acid could not explain the protective effects of dairy foods or their
      lipid extracts. Milk was more gastroprotective in stressed rats than another food
      of equal caloric value. We conclude that both the lipid and nonlipid fractions of
      dairy foods possess gastroprotective activity against stress-induced
      ulcerogenesis in rats, a property that may be of therapeutic value for man.

PMID- 7587806
TI  - Intraepithelial cells with irregular nuclear contours as a marker of esophagitis
      in children with gastroesophageal reflux disease.
AB  - The diagnostic usefulness of intraepithelial cells with irregular nuclear
      contours (CINC) (squiggle cells) in esophageal biopsies was investigated in 76
      children (range age: 6 months-12 years) with gastroesophageal reflux disease. A
      further 20 subjects (range age: 10 months-11 years) served as controls. Based on
      the microscopic changes of the esophagus, according to traditional histological
      criteria, four groups of patients were identified; esophagitis was severe in 27,
      moderate in 20, mild in 21, and 8 patients had no clear-cut evidence of
      microscopic esophagitis. Data are given as mean +/- SD. Intraepithelial CINC had
      an immunohistochemical profile consistent with T lymphocytes. Patients with
      severe esophagitis had a CINC density (number per high-power filed) (9.0 +/- 3.5)
      significantly higher than patients with mild esophagitis (7.0 +/- 3.0) and those
      without evidence of microscopic esophagitis (6.5 +/- 1.9) (P < 0.05), but not
      different from those with moderate esophagitis (8.0 +/- 3.6); in all patients
      groups the CINC density was higher than in controls (2.2 +/- 0.3) (P < 0.01). The
      percentage of reflux at 24-hr intraesophageal pH monitoring was higher in severe
      esophagitis patients (11.4 +/- 6.0) as compared to the other groups (moderate:
      7.8 +/- 6.3; mild: 6.5 +/- 3.6; no microscopic esophagitis: 6.3 +/- 2.0; P <
      0.05). There was no correlation between CINC density and the amount of
      intraesophageal acid exposure in all patients. Furthermore, 27 of our patients
      had a normal intraesophageal acid exposure at the prolonged pH test (24-hr % of
      reflux < or = 4.5): the CINC density was significantly higher in them than in the
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587802
TI  - Idiopathic megarectum in adults. An assessment of manometric and radiologic
      variables.
AB  - Outlet obstruction is thought to be one of the major factors responsible for
      idiopathic constipation. However, outlet obstruction itself may be due to several
      mechanisms. Among these, the presence of a megarectum is a leading one.
      Pathophysiological studies in adult patients with idiopathic megarectum are
      scarce. We studied by manometric and defecographic means 15 adult subjects with
      idiopathic megarectum and severe chronic constipation. Twenty-five healthy
      volunteers of both sexes acted as controls. Manometric variables showed
      significant differences between patients and controls with respect to internal
      anal sphincter pressure (P = 0.02), minimum relaxation volume (P < 0.001),
      defecatory sensory threshold (P < 0.001), mean rectal tolerable volume (P <
      0.001), and rectal compliance (P < 0.001). An altered response to straining was
      observed in 46.6% of patients and in 12% of controls (P < 0.04); the ability to
      expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P <
      0.001). Although all patients opened the anorectal angle and had descent of the
      pelvic floor, thereby confirming an adequate expulsion effort, evacuation of
      contrast material appeared extremely difficult. In fact, no subject was able to
      expel more than 30% of the rectal contents during fluoroscopic screening. These
      results confirm previous hypotheses that idiopathic megarectum displays features
      of a neuropathic process as an underlying mechanism. Further studies are needed
      that also take into consideration the muscle tone component of the rectum in
      these patients.

PMID- 7587805
TI  - Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal
      injury.
AB  - The objectives of this study were to determine the roles of neutrophil
      endothelial cell interactions and oxygen-derived free radicals in the
      pathogenesis of aspirin-induced gastric mucosal injury in rats. Oral
      administration of acidified aspirin (200 mg/kg) resulted in linear hemorrhagic
      erosions and an increase in myeloperoxidase activity, an index of neutrophil
      infiltration, in the gastric mucosa. Aspirin-induced gastric damage and the
      increase in myeloperoxidase activity were significantly inhibited by the
      injection of anti-CD11a, anti-CD11b, anti-intercellular adhesion molecule-1
      monoclonal antibodies, and the combination of superoxide dismutase and catalase,
      which are scavengers of active oxygen species. These results suggest that
      neutrophil-endothelial adhesive interactions, which occur via CD11a/ CD18- and
      CD11b/CD18-dependent interactions with intercellular adhesion molecule-1, and
      oxygen-derived free radicals produced by neutrophils are implicated in the
      production of aspirin-induced gastric mucosal injury.

PMID- 7587807
TI  - Role of dorsal motor nucleus of vagus in gastric function and mucosal damage
      induced by ethanol in rats.
AB  - Experimental evidence indicates that the autonomic nervous system, especially the
      cholinergic pathway modulates the mucosal defensive mechanism and affects mucosal
      damage in the stomach. The present study investigated the role of the dorsal
      motor nucleus of vagus (DMV) in gastric function and its influences on ethanol
      induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion
      of the DMV as compared with sham operation and lesions of other brain areas, eg,
      nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal
      gastric mucosal blood flow (GMBF) and also the blood flow after ethanol
      administration. The same operation did not affect the acid secretion either in
      the basal state or during the ethanol treatment period. Lesions at the caudal
      half of the DMV produced a bigger depression of GMBF when compared with lesion at
      the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic
      lesions in the gastric glandular mucosa, and this was significantly potentiated
      by lesions at the DMV, especially in the caudal half. The present findings
      indicate that acute DMV damage at the caudal half markedly affects the GMBF but
      not the acid secretion. The action on GMBF may contribute to the aggravation of
      ethanol-induced gastric damage in rats. These data reinforce the idea that the
      central vagal pathway, especially the caudal half of the DMV, plays a significant
      role in the modulation of GMBF, which in turn affects the integrity of gastric
      mucosal barrier.

PMID- 7587809
TI  - Effect of plaunotol on superoxide production activity in vivo.

PMID- 7587811
TI  - Evidence for apical Na+/H+ exchanger in bovine main pancreatic duct.
AB  - The finding of a high PCO2 in basally secreted pancreatic juice of man and dog
      raises the hypothesis of proton secretion from ductal epithelial cells presumably
      through a Na+/H+ exchanger. To test this possibility, H+ luminal secretion and
      Na+ movements were measured in vitro on samples of bovine pancreatic ducts
      mounted in Ussing-type chambers. The rate of luminal acidification measured by
      the pH stat method, using bicarbonate-free media gassed with 100% O2, reached
      2.75 muEq/cm2/hr. Proton secretion was blocked in the presence of 1 nM amiloride
      or in the absence of Na+ (replaced by choline) in the mucosal solution. Study of
      transepithelial 22Na fluxes in short-circuited tissue, bathed on both sides by
      control Ringer solution, gassed by 95% O2-5% CO2 demonstrated a net sodium
      transport from the mucosal to the interstitial side of the duct (net 22Na flux =
      3.23 +/- 0.8 muEq/cm2/hr). This net sodium transport was electroneutral and
      blocked by mucosal amiloride (0.5-1 mM/liter) or by interstitial ouabain (1
      mM/liter). These results are consistent with the existence of a Na+/H+ exchanger
      on the luminal side of the bovine main pancreatic duct.

PMID- 7587808
TI  - Effects of a novel 5-HT1A receptor agonist, E4424, on gastric adherent mucus
      levels following restraint stress in rats.
AB  - Several novel arylpiperazine serotonin 1A receptor agonists, developed as
      anxiolytics, have antisecretory and gastroprotective effects in rats. E4424 (2-?4
      [4-(4-chloropyrazol-1-yl)butyl]-1-piperazinyl ?pyrimidine; Lesopitron
      dihydrochloride), has potent anti-gastric secretory and antiulcer effects.
      Preliminary data indicated an enhancing effect of E4424 on gastric mucus that may
      underlie its gastroprotective actions. We therefore tested the effects of acute
      and chronic administration of E4424 and of a reference 5-HT1A receptor agonist, 8
      OHDPAT [8-hydroxy-2-(di-n-propylamino)tetralin], on gastric mucus levels in rats
      subjected to cold-restraint stress, a procedure associated with depletion of
      gastric mucus and the development of mucosal injury. Acute oral administration of
      E4424 increased adherent mucus levels by 12%, 11%, and 13%, relative to controls.
      Chronic E4424 significantly increased gastric mucus relative to controls (69%
      increase). Acute oral treatment with 8-OHDPAT did not affect gastric mucus level.
      Acute intraperitoneal 8-OHDPAT slightly increased mucus levels. Chronic twice per
      day 8-OHDPAT did not affect mucus levels; however, chronic once per day treatment
      with 8-OHDPAT significantly elevated gastric mucus levels at the highest doses
      used. For E4424, there is a strong correlation between reduction of gastric
      mucosal injury and increase in gastric mucus level, suggesting that the action of
      E4424 on glandular mucus levels is an important mechanism underlying its
      gastroprotective effects.

PMID- 7587812
TI  - Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment
      of severity of acute pancreatitis. Comparison with serum C-reactive protein.
AB  - The aim of this study was to compare the sensitivity, specificity, and diagnostic
      accuracy of serum interleukin-6, interleukin-8, beta 2-microglobulin, and C
      reactive protein in the assessment of the severity of acute pancreatitis using
      commercial kits for their respective assays. Thirty-eight patients with acute
      pancreatitis (25 men, 13 women, mean age 59 years, range 16-97) were studied; the
      diagnosis was based on prolonged upper abdominal pain associated with a twofold
      increase of serum lipase, and it was confirmed by imaging techniques. According
      to the Atlanta criteria, 15 patients had severe illness and 23 had mild disease.
      The four serum markers were determined in all patients on admission, as well as
      daily for the following five days. On the first day of the disease, the
      sensitivity (calculated on patients with severe pancreatitis), specificity
      (calculated on patients with mild pancreatitis), and the diagnostic accuracy of
      these serum markers for establishing the severity of acute pancreatitis were
      100%, 86%, and 91% for interleukin-6 (cutoff level 2.7 pg/ml); 100%, 81% and 88%
      for interleukin-8 (cutoff level 30 pg/ml); 58%, 81%, and 73% for beta 2
      microglobulin (cutoff level 2.1 mg/liter); and 8%, 95%, and 64% for C-reactive
      protein (cutoff level 11 mg/dl). The results of our study indicate that, when
      assayed during the first 24 hr of disease onset, interleukin-6 and interleukin-8
      are better markers than beta 2-microglobulin or C-reactive protein for evaluating
      the severity of acute pancreatitis.

PMID- 7587813
TI  - Dose-dependent effect of continuous subcutaneous verapamil infusion on
      experimental acute pancreatitis in mice.
AB  - Calcium antagonists may limit experimental tissue injury by membrane
      stabilization. We studied the effects of verapamil on pancreatic ultrastructure
      and zymogen extraction during diet-induced acute pancreatitis. Acute pancreatitis
      was induced in female Swiss-Webster mice by feeding a choline- and methionine
      deficient diet (CD) supplemented with 1% ethionine (CDE). Varying doses of
      verapamil in normal saline were infused continuously at a rate of 0.5
      microliter/hr for 96 hr through subcutaneously implanted osmotic pumps. The
      pancreata were examined blindly by light microscopy and by electron microscopy.
      Zymogen extracted from pancreatic tissue was measured and expressed per gram of
      protein. Mean histological scores, calculated according to a formula that
      incorporates the extent of necrosis, inflammation, acidophilia, and edema, were
      14.1 +/- 4, 10.3 +/- 2, 9.9 +/- 4, 5.9 +/- 7, 12.5 +/- 4, and 12.7 +/- 4 for CDE
      fed animals receiving 0, 0.14, 0.28, 0.56, 0.84, and 1.12 microM verapamil daily,
      respectively. Animals fed normal diet or CD had scores of 0 +/- 0. Histological
      scores were significantly lower in animals treated with 0.56 microns verapamil
      compared to animals who received no verapamil (p < 0.05) and was associated with
      reduced dissolution of the zymogen granule membrane on EM. Mean extracted
      trypsinogen and chymotrypsinogen content were reduced in the CD- and CDE-fed
      mice. The reduction in mean trypsinogen content reached statistical significance
      in CDE-fed mice treated with verapamil 0.56 microM daily. Mean chymotrypsinogen
      content was also significantly reduced CD-mice and in mice treated with 0.56
      microns and 0.84 microM of verapamil daily. Increasing doses of verapamil protect
      against diet-induced pancreatitis in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587814
TI  - New chronic pancreatitis model with diabetes induced by cerulein plus stress in
      rats.
AB  - To establish a new experimental model of chronic pancreatitis (CP) with diabetes,
      we investigated pancreatic endocrine function, blood flow, and histopathology in
      CP induced by repetition of cerulein injection plus water immersion stress in
      rats. CP rats were treated with water immersion stress for 5 hr and two
      intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a
      week for 16 weeks. In the CP group, pancreatic contents of protein, amylase,
      elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the
      control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body
      wt), blood glucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD)
      at 30 min and was significantly higher than the control group (126.3 +/- 15.4
      mg/dl)(P < 0.05). Two of seven rats in the CP group showed an obvious diabetic
      insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the
      control group (1133.4 +/- 242.0 pM)(P < 0.001). However, insulin content in the
      pancreas was 12.37 nmol/pancreas). In CP rats, winding and dilatation of surface
      blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and
      destruction of lobular architecture were also demonstrated microscopically,
      although the structure of each pancreatic islet was preserved and each islet was
      fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow
      by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was
      significantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P <
      0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a
      new CP model with diabetes in rats, in which the glucose tolerance was impaired
      without loss of insulin reserve.

PMID- 7587810
TI  - Gallbladder motility, gallstones, and the surgeon.
AB  - Cholecystectomy is one of the commonest surgical procedures in the Western world,
      with more than half a million procedures performed annually in the United States
      alone. In recent years, studies of gallstone pathogenesis and gallbladder disease
      have increasingly focused on abnormal gallbladder motility in the pathogenesis of
      some, if not all, gallbladder conditions. The control of gallbladder motility is
      complex and depends on an intricate interplay of neural and hormonal factors. An
      understanding of the control of gallbladder motility is crucial to the
      understanding of the mechanisms of gallstone formation and may help to explain
      the failure to cure symptoms after cholecystectomy in up to one third of
      patients. The purpose of this article is to outline mechanisms controlling
      gallbladder motility, examine recent developments in our understanding of this
      complex process, and relate changes in motility to common disease conditions of
      the gallbladder. The role of altered motility in the pathogenesis of gallstones
      is discussed and the effects of commonly performed surgical procedures such as
      truncal vagotomy and cholecystectomy on upper gut physiology are reviewed.

PMID- 7587817
TI  - Esophageal heterotopic pancreas presenting as an inflammatory mass.
AB  - A 47-year-old female presented with complaints of epigastric pain, poor appetite,
      and dysphagia. Abdominal CT and esophagogastroduodenoscopy revealed a 9-cm mass
      extrinsic to the distal esophagus. Esophagogastrectomy was performed. The distal
      esophagus contained multiple foci of heterotopic pancreatic tissue. There was
      associated inflammation and fat necrosis in the surrounding periesophageal soft
      tissue. Heterotopic pancreas is uncommon in the esophagus, with only a few
      reports appearing in the English literature. The clinical features of heterotopic
      pancreas, and the pathophysiology of the associated inflammatory lesion is
      discussed.

PMID- 7587816
TI  - Biliary obstruction due to pancreatic insulinoma.
AB  - Pancreatic insulinomas are rare tumors and their association with polycystic
      disease of the liver is uncommon. We report here a patient with pancreatic
      insulinoma with hepatic metastasis and biliary obstruction presenting with
      neuroglycopenic symptoms and cholestasis on a background of polycystic liver
      disease.

PMID- 7587815
TI  - Effect of propofol on human sphincter of Oddi.
AB  - The effect of propofol was studied in 11 patients who had common bile duct
      sphincter of Oddi manometry for suspected dysfunction. Patients were initially
      sedated with midazolam and then further or resedated with propofol for the second
      set of pressure measurements. Recordings were made about 10 min after giving each
      drug. No patient had elevated basal pressure initially. Average basal pressure
      was unchanged (16.7 +/- 16.4 mm Hg), phasic contraction frequency was unchanged
      (3.4 +/- 3.8/min), and phasic contraction amplitude fell but did not achieve
      statistical significance (91.8 +/- 77.3 mm Hg, P = 0.1). There was no difference
      in lowest blood pressure, pulse, or oxygen saturation recorded during midazolam
      or propofol sedation. Subjectively, the patients were more sedated during
      propofol administration. It is concluded that propofol is a safe and effective
      agent for conscious sedation. It does not alter the sphincter of Oddi pressure
      profile in patients with normal basal sphincter pressures and thus could be used
      as an alternative and perhaps better form of sedation for ERCP with sphincter of
      Oddi manometry.

PMID- 7587818
TI  - Gallbladder and pancreatic dysfunction in celiac disease.

PMID- 7587819
TI  - Migrating motor complex and sleep in health and irritable bowel syndrome.
AB  - The human migrating motor complex (MMC) and sleep cycle have a similar
      periodicity, and there is some contention as to whether these biorhythms are
      linked. In irritable bowel syndrome (IBS), episodes of intestinal dysmotility
      have been described almost exclusively during wakefulness, but IRS patients often
      complain of poor sleep, and it has been suggested that IBS patients have
      increased rapid eye movement (REM) sleep. This study sought to identify any
      associations between sleep stage and small intestinal motility and any objective
      sleep abnormalities in IBS. Nocturnal motility was recorded from six small
      intestinal sensors mounted on a fine nasoenteric catheter in eight IBS patients
      and 10 healthy volunteers. Polysomnography to determine sleep stage was recorded
      simultaneously. The proportions of time awake, in non-REM and REM sleep was
      similar in controls and IBS. REM latency did not differ between the two groups
      despite increased depression in the IBS patients (Hamilton Depression Rating of
      8.3 +/- 1.7 in IBS, 3.0 +/- 0.7 in controls, P < 0.01). Nocturnal motility was
      similar, with phase I occupying most of the MMC cycles. There was no temporal
      association between MMCs and sleep stage, with no synchrony of phase III for REM
      episodes. The mean motility index of 4.5 +/- 0.4 during wakefulness was greater
      than during all sleep stages (P < 0.05). During non-REM sleep stages 1 and 2,
      motility index of 3.2 +/- 0.3 was greater than 2.3 +/- 0.2 during stages 3 and 4
      (P < 0.05), but similar to motility index of 3.3 +/- 0.4 during REM sleep. This
      sleep architecture and nocturnal small intestinal motility are normal in
      IBS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587820
TI  - Effect of nitroblue tetrazolium on NO synthase and motor function of opossum
      esophagus.
AB  - Nitric oxide mediates neuromuscular events in the opossum esophagus. The NADPH
      diaphorase stain is used to localize nitric oxide synthase-containing enteric
      neurons. Cells stain by the NADPH diaphorase technique because they reduce
      nitroblue tetrazolium to the visible formazan. The effects of nitroblue
      tetrazolium on neuromuscular function and nitric oxide synthase of esophageal
      muscle were studied. The NADPH diaphorase stain was performed. Nitroblue
      tetrazolium inhibited lower esophageal sphincter relaxation, abolished the
      latency gradient of the off response, and inhibited nitric oxide synthase. The
      NADPH diaphorase technique stained myenteric plexus nerve cell bodies and nerve
      processes. Nitroblue tetrazolium is not a nonspecific muscle or nerve toxin, as
      nerve-mediated cholinergic responses, responses to exogenous nitric oxide, and
      responses to myogenic stimulation were maintained after nitroblue tetrazolium
      abolished the off response and lower esophageal sphincter relaxation. Nitroblue
      tetrazolium inhibits nitric oxide-mediated events and nitric oxide synthase. It
      stains neurons in the esophageal myenteric plexus.

PMID- 7587822
TI  - Focal nodular hyperplasia of the liver without central scar.
AB  - An unusual case of focal nodular hyperplasia (FNH) of the liver is presented. A
      31-year-old male was admitted to our hospital for the evaluation of an hepatic
      mass 10 cm in diameter located in segment 4. Routine examinations including liver
      function tests were all normal. Hepatitis B surface antigen, hepatitis C virus
      antibody, alpha-fetoprotein were all negative. Imagining studies could not detect
      specific findings of FNH such as a central scar structure or a spoke-wheel
      appearance due to dilated tumor vessels coursing centrally followed by radiating
      peripheral coursing vessels. Extensive left lobectomy of the liver was performed.
      Histological examination of the specimen cut into 1-cm-thick slices revealed no
      central stellate scars. Preoperative diagnosis of FNH with imaging studies was
      difficult because of the absence of central scars.

PMID- 7587823
TI  - Suprahepatic gallbladder and right lobe anomaly of the liver in patients with
      biliary cancers.
AB  - The suprahepatic region is a rare ectopic location of the gallbladder. It usually
      combines with right lobe anomaly of the liver. Here we report two unusual cases
      of suprahepatic gallbladder with agenesis or hypogenesis of the right lobe of the
      liver and biliary cancer. A patient with a gallbladder tumor was admitted to our
      emergency room with acute cholecystitis and liver abscess. Imagining examinations
      and operation confirmed the suprahepatic position of gallbladder, agenesis of the
      right lobe, and dissemination of gallbladder cancer. In the patient with
      cholangiocarcinoma, CT scans and percutaneous transhepatic cholangiography
      documented the presence of a hilar tumor and hypogenesis of the right lobe. Both
      of these patients died from biliary tract cancer soon after operation.

PMID- 7587821
TI  - Effect of splenectomy on hepatic metastasis of colon carcinoma and natural killer
      activity in the liver.
AB  - We have previously demonstrated that administration of killed streptococcal
      preparation (OK432), a biological modifier, increased the number of asialo GM1
      positive cells in the liver, enhanced NK activity of hepatic mononuclear cells,
      and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were
      inoculated into the superior mesenteric vein of C57BL/6 strain mice. In the
      present study, to clarify the role of the spleen in immune surveillance of the
      liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on
      hepatic NK activity has been examined. The number of hepatic metastasis increased
      in the splenectomized mice, compared with that in sham-operated mice.
      Administration of OK432 increased the number of asialo GM1-positive cells in the
      liver and enhanced NK activity of hepatic mononuclear cells in both groups, but
      NK activity of hepatic mononuclear cells in the splenectomized mice was less than
      that of the sham-operated mice. An enhanced NK activity of these cells was
      abolished by treatment with anti-asialo-GM1 antibody plus complement in vitro.
      Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432
      administration and persisted until 8 hr, but was scarcely noted in the liver. On
      the other hand, NK activity of hepatic mononuclear cells in the asialo GM1
      positive cell-depleted (previous administration of antiserum against asialo GM1)
      mice was enhanced after OK432 administration in the sham operated and
      splenectomized mice, but an enhanced NK activity in these mice was only partially
      or not at all abolished by treatment with anti-asialo GM1 antibody plus
      complement in vitro, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587825
TI  - Monokine production by peripheral whole blood in chronic hepatitis C patients
      treated with interferon.
AB  - Using our scoring system, we studied the production of monokines (interleukin-1
      alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6) by
      lipopolysaccharide-stimulated peripheral whole blood in 34 patients with chronic
      hepatitis C during the interferon-alpha/beta therapy. It decreased in 25.7% (9/35
      group A), fluctuated in 60.0% (21/35, group B), and increased in 14.3% (5/35,
      group C). The patients in group A were younger than those in group B (P < 0.05).
      The histological grade of injury was milder in group A than in group B or C. The
      rate of sustained response was 66.7% (6/9) in group A, 19.0% (4/21) in group B,
      and 40.0% (2/5) in group C(P = 0.0184, group A versus group B). In summary,
      monokine production by peripheral whole blood varied during interferon therapy
      for chronic hepatitis C patients. No significant change was noted in 60% of the
      patients. However, patients with decreased monokine production were younger, with
      a mild histological grade, and likely to respond to the interferon therapy.

PMID- 7587826
TI  - Elevated serum iron predicts poor response to interferon treatment in patients
      with chronic HCV infection.
AB  - To date, there are no firm clinical, demographic, biochemical, serologic, or
      histologic features predicting which patients with chronic hepatitis C are more
      likely to respond to therapy with interferon-alpha. Serum iron, total iron
      binding capacity, transferrin saturation, and ferritin were measured in the
      fasting state. The amount of stainable iron in liver biopsy specimens was
      evaluated histochemically as well. All patients received subcutaneous recombinant
      human IFN-alpha 2a three million units thrice weekly by self-administration.
      Eleven of 13 (84%) responders had low to normal serum iron levels as compared to
      one of 26 (4%) nonresponders (P < 0.001). The serum transferrin was similar in
      both groups, but iron saturation was significantly lower in responders (30 +/-
      10%) than in nonresponders (53 +/- 12%) (P< 0.001). Serum ferritin and hepatic
      iron content were higher in nonresponders (NS). It is suggested that increased
      serum iron and transferrin saturation blunt the action of interferon, as they
      have opposite effects on the immune system. Iron overload can thus lead to a poor
      response to interferon. It remains to be seen whether reducing iron overload will
      improve the response to interferon therapy.

PMID- 7587824
TI  - [13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose
      oral contraceptives.
AB  - The [13C]aminopyrine breath test measures hepatic mixed function oxidase
      activity. The cumulative percent dose recovered over 2 hr is a sensitive
      indicator of hepatic dysfunction; values < or = 7.0% have been shown to indicate
      severe liver disease. Previous studies have suggested that the test results may
      be influenced by the use of oral contraceptives steroids. We compared the results
      from five non-oral contraceptive-using women with those from 31 women whose
      duration of oral contraceptive steroid usage ranged from 4 to 204 months. The
      women were taking one of four oral contraceptive formulations that differed in
      the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and
      progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5,
      0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and
      28 of the menstrual cycle. Cumulative percent dose recovery values among the
      normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/
      1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid
      users showed a marked reduction in cumulative percent dose recovery at 21 days,
      averaging 6.1 +/- 2.3% (P < 0.001), and returned to normal values (10.2 +/- 3.5%)
      at 28 days in most women(seven days after oral contraceptive steroid usage was
      paused). The adverse impact on hepatic mixed function oxidase by oral
      contraceptive formulations did not differ on the basis of estrogen or
      progesterone content. The adverse impact of oral contraceptive usage on the mixed
      function oxidase activity measured by the [13C]aminopyrine breath test must be
      considered for women of childbearing potential.

PMID- 7587827
TI  - Severe chronic active hepatitis induced by UFTR containing tegafur and uracil.
AB  - A 77-year-old female patients developed severe hepatic injury after the
      administration of UFTR, which contains tegafur and uracil, for postoperative
      chemotherapy of colon cancer. Liver damage was recognized 10 months after its
      administration. Serum markers for viral hepatitis and various autoantibodies were
      negative. The wedged biopsied liver specimen revealed advanced chronic active
      hepatitis with periportal confluent necrosis, marked intralobular spotty
      necrosis, and significant proliferation of pseudo-bile ductules. Although the
      cessation of the drug and conservative therapies improved hepatic function, an
      accidental readministration of UFTR caused her severe hepatic damage again. These
      findings suggest that liver injury in the present case was caused by UFTR.
      Histological findings were unique. Although tegafur is known to worsen hepatic
      function when given to patients with liver cirrhosis, UFTR may also cause severe
      hepatic injury in those without preexisting liver disease.

PMID- 7587829
TI  - Effect of oral erythromycin on colonic transit in patients with idiopathic
      constipation. A pilot study.
AB  - Erythromycin, a motilin receptor agonist has been shown to have prokinetic
      effects on the upper gastrointestinal tract and gallbladder. Colonic effects of
      the drug are controversial, and it is debated whether human colon contains
      motilin receptors. In this study we evaluated the effects of erythromycin on
      colonic transit and stool frequency in 11 patients with idiopathic constipation
      over a 1-month period in an open study. The dose used was 1 g/day for two weeks
      followed by 500 mg/day for another two weeks. The mean (SE) total and segmental
      colonic transit was measured before and seven days after therapy in seven of
      these patients. A daily record of stool frequency was maintained in all 11
      patients. Erythromycin shortened the total colonic transit from 86.2 (14.6) to
      44.8 (8.99) hr (P < 0.01); however, segmental transit studies revealed a
      significant effect (P < 0.01) only in the right colon and rectosigmoid region. No
      significant side effects were observed with short-term therapy. These preliminary
      results suggest that erythromycin is of therapeutic value in patients with
      idiopathic constipation.

PMID- 7587828
TI  - Crypt-villus differentiation reflected by lectin and protein binding to rat small
      intestinal brush border membranes.
AB  - To compare differentiation along the crypt-villus axis in adult rats with changes
      observed in postnatal maturation with respect to binding capacities for lectins
      and food proteins, crypts and villi were isolated by in vivo perfusion and in
      vitro incubation. Brush border membranes were prepared from adults and newborns,
      and binding of 125I-labeled lectins and food proteins was assessed by airfuge
      ultracentrifugation. Crypt and villus membrane protein patterns looked almost
      identical, unlike newborn membranes. Considerable shifts in lectin binding to
      membranes were observed during postnatal maturation, but not in crypt-villus
      differentiation. For instance, fucose-specific lectin binding patterns in both
      preparations resembled the general adult mode. Contrary to differences in food
      protein binding between newborn and adult membranes, food protein binding did not
      show a consistent significant difference between membranes of crypt and villus
      origin in adult animals. In conclusion, membrane differentiation along the crypt
      villus axis was found to follow a pattern dissimilar from neonatal maturation as
      far as protein and carbohydrate composition and food protein binding were
      concerned.

PMID- 7587832
TI  - Functional ablation of sensory neurons impairs healing of acute gastric mucosal
      damage in rats.
AB  - Healing of ethanol-injured gastric mucosa was studied in rats treated with a
      neurotoxic dose of capsaicin to induce functional ablation of sensory nerves.
      Capsaicin treatment delayed the healing of mucosal damage in the glandular region
      and promoted the development of deep ulcerations predominantly in the antrum.
      These lesions occupied 86% of the antral surface and were associated with marked
      invasion of inflammatory cells and 18-fold elevation of gastric myeloperoxidase
      activity compared with vehicle-pretreated rats. Inhibition of cyclooxygenase, 5
      lipoxygenase, or nitric oxide synthase did not affect the development of antral
      lesions after ethanol challenge in capsaicin-pretreated rats. In vehicle
      pretreated rats, inhibition of nitric oxide synthase did not mimic the effect of
      functional ablation of sensory neurons. The findings suggest that in the gastric
      mucosa sensory neurons contribute to repair processes and limit the inflammatory
      response to injury. These effects do not involve arachidonic acid metabolites or
      nitric oxide.

PMID- 7587830
TI  - Nitric oxide synthase and VIP distribution in enteric nervous system in
      idiopathic chronic constipation.
AB  - Idiopathic chronic constipation has been correlated to neural abnormalities that
      consist of a reduced number of myenteric plexus neurons and a decreased
      concentration of VIP-positive nerve fibers within the circular muscle. Recent
      studies hypothesized the involvement of nitric oxide in motility disorders of the
      human gut. To date, no information is available on nitric oxide involvement in
      idiopathic chronic constipation. The density of VIP- and nitric oxide-producing
      neurons was evaluated by immunocytochemistry using anti-VIP and anti-nitric oxide
      synthase antibodies in five patients with idiopathic chronic constipation. A low
      total neuron density was found at the myenteric plexus. The density of VIP
      positive neurons was low while that of nitric oxide synthase-positive neurons was
      high at both plexuses. Our data confirm that idiopathic slow-transit chronic
      constipation is due to abnormal neurogenic factors. The presence of numerous
      nitric oxide synthase-positive neurons, all along the colon and at both plexuses,
      supports the hypothesis that an excessive production of nitric oxide may cause
      the persistent inhibition of contractions.

PMID- 7587831
TI  - Effect of Bacteroides melaninogenicus culture supernatant and deconjugated bile
      salt on lipid absorption.
AB  - Lipid malabsorption is a common clinical manifestation of small bowel bacterial
      overgrowth. Its pathogenesis, however, remains controversial. Bacteroides
      melaninogenicus ssp. intermedius, an anaerobic bacterium, is commonly isolated
      from the upper bowel of patients with small intestinal bacterial overgrowth. The
      effects of a culture supernate of this organism and deoxycholate, an unconjugated
      bile salt, on intestinal oleic acid absorption were examined using a rat closed
      loop model. The supernatant reduced the in vitro uptake of oleic acid by 19% (P<
      0.001). Deoxycholate did not significantly reduce the lipid absorption. Combined
      supernate and deoxycholate did not have an additive effect on absorption of oleic
      acid. We conclude that anaerobic bacterial products may contribute to the
      malabsorption of lipid in the setting of bacterial overgrowth of the small bowel.

PMID- 7587833
TI  - Measurement of gastric and duodenal mucosal protein turnover in humans.
AB  - Conventional measurement of mucosal turnover is based on labeling cellular DNA
      with [3H]thymidine, but because of the risk of genetic damage, this technique is
      not suitable for studies in normal human subjects. Consequently, we have measured
      mucosal protein turnover by a primed/continuous intravenous infusion of tracer
      quantities of [1-14C]leucine and measured its incorporation into mucosal protein
      at 4 hr in nine healthy adult volunteers. Mucosal samples were obtained by
      standard endoscopic techniques from the distal duodenum and gastric antrum. In
      addition, duodenal villous height and width were measured by microscopic
      micrometric techniques in order to calculate villous growth rate. Results
      demonstrated a mucosal protein turnover of 57 +/- 5% day in gastric antrum and 39
      +/- 2% day in duodenum, suggesting a mucosal replacement rate of 1.8 and 2.6
      days, respectively. Average duodenal villous height was 433 +/- 77 micron,
      suggesting a villous growth rate of approximately 160 microns/day. As our mucosal
      protein turnover rates are similar to epithelial turnover rates measured by
      cellular labeling techniques, our results support the "intestinal proliferation"
      theory that suggests all mucosal elements follow similar turnover
      characteristics. In conclusion, the technique should provide a practical
      alternative method of studying the effect of disease upon mucosal regeneration
      and repair.

PMID- 7587834
TI  - Rebamipide, novel prostaglandin-inducer accelerates healing and reduces relapse
      of acetic acid-induced rat gastric ulcer. Comparison with cimetidine.
AB  - This study was done to elucidate whether rebamipide during the initial period of
      acetic acid-induced gastric ulcer affected healing and future ulcer relapse. The
      cumulative healing rate was higher in rats given rebamipide alone or those given
      rebamipide and cimetidine during and after administration, but not in rats given
      cimetidine alone, compared to control rats. Cumulative relapse rate was
      significantly lower in rats initially given rebamipide alone or those given
      rebamipide and cimetidine than in rats initially given cimetidine alone. These
      results suggest that rebamipide is beneficial for obtaining a better quality of
      ulcer healing and reduction of future ulcer relapse.

PMID- 7587835
TI  - Influence of Helicobacter pylori on tryptase and cathepsin D in peptic ulcer.
AB  - We here ascertain whether tryptase (a serine endoprotease released by mast cells)
      and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the
      extracellular matrix) play a part in peptic ulcer disease and whether they are
      linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients
      with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and
      CD were measured in mucosal biopsies (body and antrum of the stomach and
      duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa).
      Tryptase and CD levels were higher (25%) in patients with active peptic ulcer,
      whether gastric or duodenal. In Hp-positive patients the CD mucosal content was
      higher while tryptase mucosal levels were lower than in Hp-negative patients.
      Tryptase was correlated with gastrin content. CD seems to be mainly related to
      the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an
      indirect link between Hp infection, gastrin release, and the function of mast
      cells.

PMID- 7587836
TI  - Plasticity of myofibroblasts appearing in granulation tissues after acetic acid
      treatment. Effect of bFGF.
AB  - To clarify the origin of the myofibroblasts appearing in the healing process of
      the acetic acid-induced ulcer and effect of basic fibroblast growth factor (bFGF)
      on these myofibroblasts, we conducted an immunohistochemical study using antibody
      to intermediate filaments, desmin and vimentin. The binding sites of bFGF on the
      regenerative tissues were also studied by the radioautographic study of soluble
      compounds. As a result, the binding sites of bFGF were accumulated on the
      fibroblasts and myofibroblasts as well as on endothelial cells. The effect of
      CS23, acid-stable human recombinant bFGF was shown on distribution of
      myofibroblasts and regeneration of the microvascular system in the mucosal and
      submucosal layers.

PMID- 7587837
TI  - Healing of experimental gastric ulcers. Interference by gastric acid.

PMID- 7587838
TI  - We need to integrate new data concerning Helicobacter pylor into experimental
      ulcer research.

PMID- 7587839
TI  - Indomethacin inhibits cell proliferation and increases cell losses in rat
      gastrointestinal epithelium.
AB  - Gastrointestinal cell proliferation was estimated in histological sections of
      rats treated with low and high doses of parenteral indomethacin for 3 to 60 days.
      Mitoses were arrested with vincristine and cells in S phase were labeled with
      tritiated thymidine. Short-term, low-dose treatments reduced the mitotic activity
      in the oxyntic and small intestinal epithelium, whereas moderate doses restored
      the mitotic index and high doses increased the proliferative activity and
      produced epithelial hyperplasia. Long-term, low-dose treatments increased cell
      proliferation in the small intestine and reduced the number of villous cells.
      Indomethacin did not affect the proliferative response elicited by refeeding in
      the oxyntic mucosa, but the simultaneous administration of prostaglandin E2
      analog increased the number of arrested mitoses. The turnover of labeled cells
      was accelerated by indomethacin, particularly in the small intestine. These
      findings indicate that prostaglandins are regulators of the cell kinetics of the
      gastrointestinal epithelium but, at the same time, they disclose the presence of
      trophic mechanisms that are independent of the synthesis of endogenous
      prostaglandins.

PMID- 7587840
TI  - Present views on restitution of gastrointestinal epithelium.

PMID- 7587841
TI  - Role of epidermal growth factor in peptic ulcer healing.
AB  - In recent years, increasing interest has been focused on peptide growth factors,
      and impressive progress has been made in the understanding of their role in tumor
      development and progression. However, evidence is mounting that peptides such as
      epidermal growth factor and transforming growth factor-alpha may be of much more
      physiological than pathological importance. This brief article is intended to
      give a rapid overview of the available data supporting a role for epidermal
      growth factor and its human homologue urogastrone in peptic ulcer healing.

PMID- 7587845
TI  - Dietary factors determining diabetes and impaired glucose tolerance. A 20-year
      follow-up of the Finnish and Dutch cohorts of the Seven Countries Study.
AB  - OBJECTIVE: To investigate the role of diet as a predictor of glucose intolerance
      and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS:
      At the 30-year follow-up survey of the Dutch and Finnish cohorts of the Seven
      Countries Study, in 1989/1990, men were examined according to a standardized
      protocol including a 2-h oral glucose tolerance test. Information on habitual
      food consumption was obtained using the cross-check dietary history method. Those
      338 men in whom information on habitual diet was also available 20 years earlier
      were included in this study. Subjects known as having diabetes in 1989/1990 were
      excluded from the analyses. RESULTS: Adjusting for age and cohort, the intake of
      total, saturated, and monounsaturated fatty acids and dietary cholesterol 20
      years before diagnosis was higher in men with newly diagnosed diabetes in the
      survey than in men with normal or impaired glucose tolerance. After adjustment
      for cohort, age, past body mass index, and past energy intake, the past intake of
      total fat was positively associated with 2-h postload glucose level (P < 0.05).
      An independent inverse association with the past intake of vitamin C was observed
      (P < 0.05). These associations were independent of changes in the intake of fat
      and vitamin C during the 20-year follow-up. An increase in the consumption of
      vegetables and legumes, potatoes, and fish during the 20-year follow-up was
      inversely related with 2-h glucose level (P < 0.05). CONCLUSIONS: Although the
      regression coefficients were in general not very large, these results indicate
      that a high intake of fat, especially that of saturated fatty acids, contributes
      to the risk of glucose intolerance and NIDDM. Foods such as fish, potatoes,
      vegetables, and legumes may have a protective effect. In addition, the observed
      inverse association between vitamin C and glucose intolerance suggests that
      antioxidants may also play a role in the development of derangements in glucose
      metabolism.

PMID- 7587842
TI  - Antibodies against bovine albumin and other diabetes markers in French children.
AB  - OBJECTIVE: Findings in epidemiology and animal experimentation suggest that
      autoimmunity in insulin-dependent diabetes mellitus (IDDM) may be triggered by
      dietary cow-milk protein, particularly bovine serum albumin (BSA). Elevated IgG
      anti-BSA antibodies were found in children from Finland with newly onset
      diabetes; Finland has the highest incidence of diabetes and cow's milk
      consumption in the world. We now analyze BSA serology and other diabetes markers
      in school-age children from France, where diabetes incidence and cow's milk
      consumption are low. RESEARCH DESIGN: Sera were obtained from three groups: newly
      diagnosed diabetic (n = 43), islet cell antibody-positive (ICA+) nondiabetic (n =
      98), and ICA- healthy control children (n = 267). IgG anti-BSA antibody levels
      were measured blindly using particle concentration fluoroimmunoassays and
      analyzed in comparison with ICA titers and human leukocyte antigen-DQB genotypes.
      RESULTS: There were highly significant differences in BSA antibody levels between
      all three groups (P < 0.0001). Diabetic patients had elevated anti-BSA levels in
      74.4% of cases, compared with 5.5% of control children. In the group of ICA+ non
      diabetic children, 20% were anti-BSA-positive. Neither ICA nor BSA antibody
      titers were significantly related to DQB genotype or sex. ICA titers ( > or = 4
      Juvenile Diabetes Foundation units) were present in 84% of diabetic children. Two
      thirds of diabetic children were positive for both ICA and anti-BSA antibodies,
      and none were negative for both markers. CONCLUSIONS: Elevated IgG anti-BSA
      levels are associated with IDDM in the low-incidence French population. In newly
      diagnosed diabetic children, these antibodies have similar specificity (95 vs.
      98%) and slightly lower sensitivity for IDDM than ICA (74.4 vs. 83.7%). Our
      results may support an immunological role of BSA in diabetic autoimmunity.

PMID- 7587846
TI  - Veterans Affairs Cooperative Study on glycemic control and complications in type
      II diabetes (VA CSDM). Results of the feasibility trial. Veterans Affairs
      Cooperative Study in Type II Diabetes.
AB  - OBJECTIVE: It is not clear whether intensive pharmacological therapy can be
      effectively sustained in non-insulin-dependent diabetes mellitus (NIDDM). The
      relative risks and benefits of intensive insulin therapy in NIDDM are not well
      defined. Accordingly, we designed a feasibility study that compared standard
      therapy and intensive therapy in a group of NIDDM men who required insulin due to
      sustained hyperglycemia. RESEARCH DESIGN AND METHODS: A prospective trial was
      conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a
      known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a
      standard insulin treatment group (one morning injection per day) or to an
      intensive therapy group designed to attain near-normal glycemia and a clinically
      significant separation of glycohemoglobin from the standard arm. A four-step plan
      was used in the intensive therapy group along with daily self-monitoring of
      glucose: 1) an evening insulin injection, 2) the same injection adding daytime
      glipizide, 3) two injections of insulin alone, and 4) multiple daily injections.
      Patient accrual and adherence, glycohemoglobin (HbA1c), side effects, and
      measurements of endpoints for a prospective long-term trial were assessed.
      RESULTS: Accrual goals were met, mean follow-up time was 27 months (range 18-35
      months), and patients kept 98.6% of scheduled visits. After 6 months, the mean
      HbA1c in the intensive therapy group was at or below 7.3% and remained 2% lower
      than the standard group for the duration of the trial. Most of the decrease in
      the mean HbA1c in the intensive group was obtained by a single injection of
      evening intermediate insulin, alone or with daytime glipizide. By the end of the
      trial, 64% of the patients had advanced to two or more injections of insulin a
      day, aiming for normal HbA1c. However, only a small additional fall in HbA1c was
      attained. Severe hypoglycemia was rare (two events per 100 patients per year) and
      not significantly different between the groups, nor were changes in weight, blood
      pressure, or plasma lipids. There were 61 new cardiovascular events in 40
      patients and 10 deaths (6 due to cardiovascular causes). CONCLUSIONS: Intense
      stepped insulin therapy in NIDDM patients who have failed glycemic control on
      pharmacological therapy is effective in maintaining near-normal glycemic control
      for > 2 years without excessive severe hypoglycemia, weight gain, hypertension,
      or dyslipidemia. Cardiovascular event rates are high at this stage of NIDDM. A
      long-term prospective trial is needed to assess the risk-benefit ratio of
      intensified treatment of hyperglycemia in NIDDM patients requiring insulin.

PMID- 7587847
TI  - Physician and patient prevention practices in NIDDM in a large urban managed-care
      organization.
AB  - OBJECTIVE: To examine physician and patient adherence to prevention guidelines in
      non-insulin-dependent diabetes mellitus (NIDDM) with attention to possible
      differences in adherence by patient race or ethnicity. RESEARCH DESIGN AND
      METHODS: We performed a cross-sectional chart review study of prevention
      practices, complications, and risk factors in 378 NIDDM patients (at least 5
      years known duration) who were Permanente Medical Care Program, Oakland, CA.
      There were 232 blacks, 81 whites, 29 Hispanics, and 36 members of other
      races/ethnicities. RESULTS: Age- and duration-adjusted prevalence of 14
      complications was low and, with the exception of diabetic retinopathy, did not
      differ significantly by race. An eight-point prevention score that reflected
      recommended use of glucose, HbA1c, high-density lipoprotein/total cholesterol,
      blood pressure and proteinuria testing, ophthalmology a and foot examinations,
      and diabetes education during a 2-year period did not differ by race/ethnicity (P
      = 0.36). The mean score (4.9 +/- 1.6) indicated that on average, five of eight
      guidelines were performed appropriately. Compliance was poorest for annual
      proteinuria checks (32.2%). No differences were noted by race/ethnicity in
      referrals to ophthalmology, weight reduction, or smoking cessation or in missed
      appointments or failure to keep referral visits. CONCLUSIONS: The absence of
      racial differences in either prevention practices or complication rates in this
      insured prepaid setting suggests that improved access to preventive services may
      be effective in reducing such differences nationally. However, adherence to
      several guidelines was < or = 50%, indicating that physicians are not
      sufficiently convinced of the necessity for these prevention measures.

PMID- 7587844
TI  - Serum sialic acid concentration and coronary heart disease in NIDDM.
AB  - OBJECTIVE--To examine the association between serum sialic acid concentrations
      and coronary heart disease (CHD) in a cross-sectional study of non-insulin
      dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--NIDDM patients
      (n = 145) attending a diabetic clinic were studied. CHD status was assessed by
      questionnaire and electrocardiogram coding, and potential risk factor assessment
      included measurement of fasting serum lipid and lipoprotein concentrations, blood
      pressure, and urinary albumin excretion rate (AER). RESULTS--Male NIDDM patients
      with CHD had a higher serum sialic acid level than those without CHD: 2.56 (2.24,
      2.72) mmol/l vs. 2.24 (2.18, 2.30) mmol/l, P = 0.01, mean (95% confidence
      interval). They were also older, had a longer duration of diabetes, had a higher
      AER, had higher total triglyceride, very-low-density lipoprotein triglyceride and
      cholesterol, and lipoprotein(a) concentrations, and had a lower apolipoprotein A1
      concentration. In an age adjusted multiple lipoprotein(a), hypercholesterolemia,
      and hypertension were associated with CHD. In women, only hypertension treatment
      was associated with CHD. CONCLUSIONS--There is a strong univariate association
      between elevated serum sialic acid and CHD in men (but not women) with NIDDM.

PMID- 7587843
TI  - Serial changes in the prevalence of islet cell antibodies and islet cell antibody
      titer in children with IDDM of abrupt or slow onset.
AB  - OBJECTIVE: To elucidate the significance of clinical and immunogenic
      heterogeneity in Japanese children with insulin-dependent diabetes mellitus
      (IDDM). RESEARCH DESIGN AND METHODS: Serial changes in the prevalence of islet
      cell antibodies (ICAs) and in ICA titer were monitored for 10 years after
      diagnosis in 34 IDDM children, 17 with abrupt onset and 17 with slow onset, whose
      durations of disease were > 5 years. RESULTS: In slow-onset IDDM children, enough
      beta-cell function was maintained in the early phase of the disease within 2
      years after diagnosis. There was a high prevalence of ICAs in children with both
      forms of IDDM at the time of diagnosis (abrupt onset 94%; slow onset 82%).
      However, the decline in the frequency of ICAs in slow-onset IDDM seemed less
      marked than in abrupt-onset IDDM after a duration of > or = 1 year (47 vs. 82%, 1
      3 years; 24 vs. 47%, 3-5 years; 24 vs. 47%, 5-7 years; 18 vs. 53%, 7-10 years, P
      < 0.05). In terms of changes in ICA titer, abrupt-onset IDDM children initially
      had high ICA levels of 160-320 Juvenile Diabetes Foundation units (JDF U), but
      these titers decreased rapidly after the 1st year. On the other hand, slow-onset
      IDDM children tended to continue to be ICA+ for a relatively long period with low
      titers of 20-40 JDF U. Among 12 children who remained ICA+ for > 5 years, slow
      onset was noted in 67% while abrupt onset was seen in only 33%. CONCLUSIONS: From
      these results, we speculated that changes in ICA titer reflect the slow
      autoimmune destruction of pancreatic beta-cells. It may be probable that
      immunogenic factors as well as environmental factors could affect the clinical
      features in the early phase of IDDM in children.

PMID- 7587849
TI  - High prevalence of diabetic retinopathy and nephropathy in Polynesians of Western
      Samoa.
AB  - OBJECTIVE: To determine the prevalence of diabetic retinopathy and nephropathy
      retinopathy and nephropathy and to define associated risk factors in Polynesian
      Western Samoans with non-insulin-dependent diabetes mellitus (NIDDM) or impaired
      glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A 1991 population-based
      study in Samoan adults (ages 25-74 years) included a 75-g oral glucose tolerance
      test, anthropometric measurements, and blood pressure recordings. Subjects with
      NIDDM or IGT had 45-degree stereo photographs taken (n = 263) (three standard
      fields of the right eye), and retinopathy was graded in comparison with Airlie
      House photographs. First-morning urine samples (n = 304) were also collected from
      these subjects and from a subsample with normal glucose tolerance. Urinary
      albumin concentration (UAC) was measured by radioimmunoassay: microalbuminuria
      was defined as UAC of 30-299 micrograms/ml; and macroalbuminuria among subjects
      with Proliferative diabetic retinopathy was found in 4.5% of known diabetic
      subjects. The prevalence of elevated UAC was 15.0% in subjects with IGT, 26.0% in
      newly diagnosed diabetes subjects, and 23.4% in known diabetes subjects. For all
      diabetic subjects (n = 162), the factors independently associated with diabetic
      retinopathy (logistic regression) were duration of diabetes, fasting plasma
      glucose, and body mass index (inversely). Duration of diabetes, serum
      triglyceride concentrations, and systolic blood pressure were independently
      associated with elevated UAC in all diabetic subjects (n = 138), and fasting
      plasma glucose had borderline significance. CONCLUSIONS: Diabetic retinopathy and
      albuminuria are common in Polynesian Western Samoans. Duration of diabetes and
      level of glycemia were the most important associated factors. These data
      underline the need for cost-effective programs for the detection and early
      treatment of diabetes in Western Samoa and other developing populations with high
      susceptibility to NIDDM.

PMID- 7587851
TI  - 1,5-Anhydro-D-glucitol evaluates daily glycemic excursions in well-controlled
      NIDDM.
AB  - OBJECTIVE: To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG)
      as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG,
      HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from
      which the M-value (after Schlichtkrull) was calculated as an index of daily
      glycemic excursion. RESEARCH DESIGN AND METHODS: The subjects were 76 patients
      with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with
      diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28),
      conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy
      (MIT, n = 15). RESULTS: HbA1c values were similar among all the groups (diet, 6.9
      +/- 0.6; OHA, 7.2 +/- 0.5; CIT, 7.1 +/- 0.6; MIT, 7.2 +/- 0.5%). The MIT group
      showed a significantly higher 1,5-AG concentration (11.5 +/- 5.3 micrograms/ml),
      a significantly lower M-value (9.2 +/- 5.2), and little risk of hypoglycemia ( <
      4 mmol/l) and hyperglycemia ( > 10 mmol/l) (1.3 +/- 1.1 times/24 h) compared with
      the CIT group (6.9 +/- 3.3 micrograms/ml, 15.7 +/- 8.9, 2.2 +/- 1.6 times/24 h,
      respectively). Insulin doses (22.4 +/- 4.5 vs. 22.0 +/- 8.9 U/day), FPG (6.6 +/-
      2.2 vs. 7.4 +/- 2.4 mmol/l), and HbA1c concentrations were not significantly
      different between the CIT and MIT groups. M-values significantly correlated with
      1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations.
      CONCLUSIONS: The findings suggest that the plasma 1,5-AG concentration can be a
      useful index of the daily excursion of blood glucose, especially in patients with
      well-controlled NIDDM.

PMID- 7587848
TI  - Effects of alprazolam on glucose regulation in diabetes. Results of double-blind,
      placebo-controlled trial.
AB  - OBJECTIVE: To determine the effects of alprazolam on glucose regulation in
      anxious and nonanxious patients with poor glycemic control and establish whether
      regulatory benefits are related to anxiolytic effects of the medication. RESEARCH
      DESIGN AND METHODS: Fifty-eight patients with poor glycemic control, 16 (27.6%)
      of whom had a symptomatic generalized anxiety disorder, were entered into a
      randomized, double-blind, placebo-controlled, 8-week trial using alprazolam (up
      to 2 mg/day) as the active agent. Generalized anxiety disorder was determined in
      accordance with Diagnostic and Statistical Manual of Mental Disorders criteria,
      and anxiety symptoms were measured using the Hopkins Symptom Checklist. Glycated
      hemoglobin levels were used to determine glucose regulation. Compliance behavior
      was assessed using glucometers and medication monitors equipped with electronic
      memory. RESULTS: A statistically significant reduction in glycated hemoglobin
      level was observed in patients treated with alprazolam compared with those
      receiving placebo (-1.1 vs. -0.3%, P = 0.04). This treatment effect was not a
      function of differences in compliance behaviors. Anxiety symptoms decreased in
      both alprazolam- and placebo-treated patients with generalized anxiety disorder,
      but reduction in glycated hemoglobin level was not dependent on alleviation of
      anxiety. CONCLUSIONS: A short course of alprazolam improved glucose regulation in
      patients with a history of poor diabetes control. This effect was not directly
      related to concomitant changes in anxiety. Alprazolam treatment of anxious
      patients with poorly controlled diabetes may result in decreased anxiety and
      improved glucose regulation through independent mechanisms.

PMID- 7587852
TI  - Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves
      distal nerve conduction in experimental diabetic neuropathy.
AB  - OBJECTIVE: To determine whether lipoic acid (LA) will reduce oxidative stress in
      diabetic peripheral nerves and improve neuropathy. RESEARCH DESIGN AND METHODS:
      We used the model of streptozotocin-induced diabetic neuropathy (SDN) and
      evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF),
      electrophysiology, and indexes of oxidative stress in peripheral nerves affected
      by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA,
      in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times
      per week after onset of diabetes. RESULTS: NBF in SDN was reduced by 50%; LA did
      not affect the NBF of normal nerves but improved that of SDN in a dose-dependent
      manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited
      normal NBF. The most sensitive and reliable indicator of oxidative stress was
      reduction in reduced glutathione, which was significantly reduced in
      streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was
      improved in a dose-dependent manner in LA-supplemented rats. The conduction
      velocity of the digital nerve was reduced in SDN and was significantly improved
      by LA. CONCLUSIONS: These studies suggest that LA improves SDN, in significant
      part by reducing the effects of oxidative stress. The drug may have potential in
      the treatment of human diabetic neuropathy.

PMID- 7587850
TI  - Release of platelet plasminogen activator inhibitor 1 in whole blood is increased
      in patients with type II diabetes.
AB  - OBJECTIVE: To compare platelet plasminogen activator inhibitor 1 (PAI-1) release
      in type II diabetic patients and healthy control subjects. RESEARCH DESIGN AND
      METHODS: We studied a group of 27 diabetic patients and a group of 16 nondiabetic
      control subjects. Whole-blood platelet aggregation, defined as a decrease in
      platelet count during shaking (180 rpm) of blood samples at 37 degrees C, and
      plasma PAI-1 antigen concentrations were measured in parallel at time 0, 7.5, 15,
      30, 60, 120, and 180 min. RESULTS: Platelet aggregation did not differ
      significantly between the two groups at any time period. However, the increase in
      plasma PAI-1 antigen concentration over basal levels at time 0 was higher for the
      group of diabetic patients when compared with their matched control subjects. The
      increment of PAI-1 antigen was 61.8 +/- 29.4 vs. 35.9 +/- 13.4 ng/ml (P < 0.005,
      means +/- SD) after 180 min for the diabetic and control subjects, respectively.
      Platelet PAI-1 release was correlated to very-low-density lipoprotein cholesterol
      and triglyceride plasma levels, but not to HbA1c levels. CONCLUSIONS: Platelets
      of patients with type II diabetes release significantly more PAI-1 than platelets
      of healthy subjects at the same level of platelet aggregation. This may
      contribute to enhanced thrombosis in diabetes.

PMID- 7587853
TI  - Reproducibility of the first-phase insulin response to intravenous glucose is not
      improved by retrograde cannulation and arterialization or the use of a lower
      glucose dose.
AB  - OBJECTIVE: To determine whether the reproducibility of the first-phase insulin
      response (FPIR) measured during an intravenous glucose tolerance test is improved
      by the use of a lower glucose dose or retrograde sampling from an arterialized
      hand vein. RESEARCH DESIGN AND METHODS: Previous studies have suggested that the
      high within-subject variation of FPIR measurement of up to 110% could be reduced
      by sampling from a retrograde cannulated and arterialized hand vein opposite to
      the cubital fossa vein through which the glucose was injected or by the use of a
      lower dose of glucose. Two low-dose (glucose, 5 g/m2 injected over 30 s) and two
      standard Islet Cell Antibody Registry Users Study (ICARUS) (glucose, 0.5 g/kg
      injected over 3 min) tests were performed on seven normal subjects at 2-week
      intervals. Samples were collected simultaneously from the cubital fossa vein,
      through which the glucose was injected, and from a retrograde cannulated,
      contralateral hand vein that was arterialized by heating. FPIR was expressed as
      the sum of the insulin measurements 1 and 3 min after the completion of the
      glucose injection and as the area under the insulin curve between 0 and 10 min.
      RESULTS: Responses to the mean sum of serum insulin concentrations at 1 and 3 min
      after intravenous glucose were significantly lower for the low-dose test (mean 94
      mU/l) than for the high-dose test (mean 184 mU/l) for samples taken from the arm
      (P < 0.05); mean 0- to 10-min insulin areas were 367 and 596 mU/l for low- and
      high-dose tests, respectively (P < 0.05). Within-subject coefficients of
      variation for samples from the hand or the arm ranged from 0.33 to 17.5% and 1.3
      to 38% for successive ICARUS and low-dose tests, respectively. Reproducibility,
      measured by the coefficient of variation between successive tests for each
      protocol, was not significantly different using samples taken from the arm or the
      contralateral hand. CONCLUSIONS: The intravenous glucose tolerance test is
      reproducible when performed by the same operator over a short time span.
      Reproducibility is not significantly improved by sampling from an arterialized,
      retrograde cannulated, contralateral hand vein. There is no case for changing the
      present ICARUS protocol to incorporate retrograde cannulation or low-dose (5
      g/m2) glucose.

PMID- 7587854
TI  - Exocrine pancreatic and beta-cell function in malnutrition-related diabetes among
      north Indians.
AB  - OBJECTIVE: To compare the pancreatic exocrine and beta-cell function in the two
      variants of malnutrition-related diabetes mellitus (MRDM): fibrocalculous
      pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD).
      RESEARCH DESIGN AND METHODS: Fecal chymotrypsin (FCT) and fasting C-peptide
      levels were measured in 20 consecutive patients with FCPD and 19 with PDPD. FCPD
      was diagnosed by pancreatic calcification on ultrasonography, while the diagnosis
      of PDPD was made on the basis of low body mass index, severe diabetes requiring
      insulin therapy, and ketosis resistance on interruption of insulin. Twenty
      patients with type I diabetes and 32 healthy subjects served as control subjects.
      RESULTS: Both FCPD and PDPD patients had diminished levels of FCT when compared
      with those of control subjects and patients with type I diabetes. However, FCT
      levels were significantly lower in subjects with FCPD (median 0.4 U/g, range 0
      8.9 U/g), in comparison with those with PDPD (4.7 U/g, 0.6-40.5 U/g; P < 0.001).
      Of the FCPD patients, 13 of 20 (65%) had severe exocrine pancreatic deficiency
      (FCT < 1 U/g) vs. 3 of 19 (15.8%) PDPD subjects (P < 0.01). In comparison with
      control subjects, fasting serum C-peptide levels were significantly diminished in
      both MRDM groups. However, C-peptide levels in subjects with FCPD (mean +/- SE,
      0.22 +/- 0.04 nmol/l) and PDPD (0.26 +/- 0.04 nmol/l) were comparable.
      CONCLUSIONS: Among the two variants of MRDM, subjects with FCPD have severe
      pancreatic exocrine deficiency in comparison with those with PDPD, even though
      their C-peptide levels are comparably diminished. This suggests that the
      pathogenesis of these two entities may differ or that the genetic and/or
      environmental factors leading to exocrine damage are different.

PMID- 7587856
TI  - Comparison of bedtime NPH or preprandial regular insulin combined with
      glibenclamide in secondary sulfonylurea failure.
AB  - OBJECTIVE: To compare the effect of bedtime NPH insulin or preprandial regular
      insulin combined with glibenclamide on metabolic control in non-insulin-dependent
      diabetes mellitus (NIDDM) patients with secondary failure to sulfonylurea
      therapy. RESEARCH DESIGN AND METHODS: Eighty NIDDM patients were randomized to
      treatment with either three preprandial doses of regular insulin (daytime group
      D) or a bedtime dose of NPH insulin (nocturnal insulinization, group N), both
      regimens being combined with 10.5 mg of glibenclamide. Metabolic profiles were
      obtained at 0, 6, 16 weeks. RESULTS: Glycemic control had improved significantly
      in both groups after 4 months. Fasting blood glucose was significantly lower
      compared with baseline in both groups. The mean change +/- SD in group D was -2.8
      +/- 3.5 mmol/l and in group N -6.4 +/- 3.0 mmol/L, the reduction being more
      pronounced in group N compared with group D (P < 0.0001). HbA1c was lowered
      similarly, from 9.2 +/- 1.4 to 7.1 +/- 1.2% in group D (P < 0.0001) and from 9.1
      to 1.1 to 7.5 +/- 1.5% in group N (P < 0.0001). The total daily insulin doses
      were similar, 29 +/- 11 U in group D and 26 +/- 9 U in group N, and the
      circulating insulin levels during daytime were higher in group D than in group N.
      Total serum cholesterol and triglycerides were similarly and significantly
      lowered compared with baseline in both groups. Weight gain was more pronounced in
      group D (3.4 +/- 0.3 kg) than in group N (1.9 +/- 1.9 kg; D vs. N, P < 0.002),
      and the change was inversely correlated with initial eight but not with the
      improvement in HbA1c. CONCLUSIONS: The two insulin regimens exert similar effect
      on glucose metabolism and serum lipids in NIDDM patients on combination therapy.
      Weight gain is more pronounced in patients given insulin during the daytime when
      preprandial doses of short-acting insulin are used.

PMID- 7587857
TI  - Insulin therapy for diabetic ketoacidosis. Bolus insulin injection versus
      continuous insulin infusion.
AB  - OBJECTIVE: Despite widespread acceptance of continuous insulin infusion (CII)
      over bolus insulin injection (BII) for treatment of diabetic ketoacidosis (DKA),
      there are no population-based studies demonstrating whether CII has resulted in
      lower morbidity and mortality. RESEARCH DESIGN AND METHODS: We addressed this
      issue using a provider-linked database and retrospectively reviewing the complete
      medical records of all incidence cases of diabetes among Rochester, Minnesota,
      residents from 1950 to 1989 with a discharge diagnosis of DKA. This population
      based study describes the consequences of the widespread change in treatment
      modality outside the confines of a controlled clinical trial. RESULTS: Among the
      diabetes incident cohort, there were 59 subjects with confirmed first episodes of
      DKA during 1950-1992; 29 of 30 subjects treated with BII occurred before 1970.
      All 29 CII cases occurred between 1976 and 1992. Sex, etiology, diabetes
      duration, and age at DKA were similar for the two groups. The proportion of obese
      individuals (BII = 2/28, CII = 8/21; P = 0.01) differed between groups. The CII
      group exhibited higher glucose values (BII = 24.9 +/- 8.5 mmol/l, CII = 37.1 +/-
      15.1 mmol/l; P = 0.002) and lower bicarbonate values (BII = 7.7 +/- 3.0 nmol/l,
      CII = 6.2 +/- 2.9 nmol/l; P = 0.04) upon admission. The mean quantity of insulin
      administered was higher in the BII group than in the CII group (179 +/- 140 and
      99 +/- 70 U, P < 0.006). The outcome of hypoglycemia occurred more frequently in
      the BII group than in the CII group (BII = 8/30, CII = 1/29; P = 0.03). The
      proportion with hypokalemia, neurological deficit, myocardial arrhythmia, or
      mortality did not differ significantly between groups. CONCLUSIONS: Our findings
      suggest the introduction of CII was accompanied by a decreased incidence of
      hypoglycemia.

PMID- 7587855
TI  - Reduction of postprandial hyperglycemia in subjects with IDDM by intravenous
      infusion of AC137, a human amylin analogue.
AB  - OBJECTIVE: To demonstrate that intravenous administration of AC137 (25,28,29
      tripro-human amylin), a human amylin analogue, modulates the rate of appearance
      of glucose derived from a standard oral meal in the peripheral circulation of
      patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND
      METHODS: After the observation that a 2-h infusion of AC137 at a rate of 150
      micrograms/h, in conjunction with the subjects' usual morning insulin dose,
      decreased postprandial hyperglycemia in 6 subjects with IDDM, a double-blind
      placebo-controlled two-period crossover design in an additional 18 IDDM patients
      was undertaken to confirm and extend the observation. Based on reasoning that an
      effect to modulate the appearance of orally administered glucose would have no
      impact on the disposition of an intravenous glucose load, nine patients were
      challenged with an intravenous glucose loads (300 mg/kg), while another nine
      patients were challenged with a standardized Sustacal meal (350 kcal) during a 5
      h infusion of AC137 (50 micrograms/h). On each occasion, the subjects received
      their usual morning doses of insulin subcutaneously. The impact of the AC137
      infusion on the plasma glucose responses to these different challenges was
      assessed. RESULTS: Intravenous infusion of AC137 yielding steady state plasma
      concentrations of 225 +/- 15 pmol/l (mean +/- SE) reduced postprandial plasma
      glucose concentrations after the standardized Sustacal meal challenge. The mean
      area under the glucose curve, corrected for baseline, was reduced from -1,869 +/-
      5,562 mg.dl-1.min during placebo infusion to -28,872 +/- 4,812 mg.dl-1.min during
      AC137 infusion, P = 0.0015. In contrast, an AC137 infusion producing steady-state
      concentrations of 234 +/- 16 pmol/l had no effect on the plasma glucose profile
      after administration of an intravenous glucose load. CONCLUSIONS: AC137
      administration, in these patients with IDDM, reduced postprandial hyperglycemia
      apparently by affecting the delivery rate of glucose from the gastrointestinal
      tract. AC137 may prove to be a clinically useful addition to insulin regimens to
      facilitate the achievement of glycemic control.

PMID- 7587858
TI  - Serum lipids and lipoprotein(a) concentrations in Chinese NIDDM patients.
      Relation to metabolic control.
AB  - OBJECTIVE: To compare serum blood lipids and lipoprotein(a) [Lp(a)] levels in
      Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients and nondiabetic
      control subjects and also to determine the influence of diabetes control on serum
      Lp(a) concentration in Chinese individuals. RESEARCH DESIGN AND METHODS: We
      compared the serum blood lipids and Lp(a) levels in NIDDM patients (n = 100) and
      age- and sex-matched nondiabetic subjects (n = 100) who participated in a case
      control study. Comparisons of Lp(a) concentrations were made between a normal
      control group, a group of diabetic patients with HbA1c < 8.0%, and a group of
      diabetic patients with HbA1c of 8% or higher. RESULTS: The diabetic patients had
      higher total triglyceride, apolipoprotein B (apo B), and apo B-to-apo AI ratios,
      but lower high-density lipoprotein (HDL) cholesterol and apo AI concentrations
      than nondiabetic controls (P < 0.001, P < 0.01, P < 0.001, P < 0.05, and P <
      0.001, respectively). A similar pattern of distribution of Lp(a) levels according
      to the degree of metabolic control was seen in patients with NIDDM and
      nondiabetic controls. No correlation was observed between Lp(a) levels and total
      cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, apo AI, apo B,
      and triglyceride levels in all diabetic patients. No difference in the Lp(a)
      levels was noted between diabetic patients and nondiabetic subjects, even in
      poorly controlled diabetic patients. CONCLUSIONS: In conclusion, Lp(a) levels are
      not elevated in diabetic patients, even in poorly controlled metabolic
      conditions.

PMID- 7587859
TI  - Local reaction secondary to insulin injection. A potential role for latex
      antigens in insulin vials and syringes.
AB  - OBJECTIVE: To evaluate the possibility that latex antigens (natural rubber) can
      contribute to or cause local sensitivity at insulin injection sites. CASE: A
      subject with documented local cutaneous allergic reactions at the site of insulin
      injections and with systemic latex allergy manifested as anaphylaxis was tested
      with intradermal injections of insulin diluent from two manufacturers and with
      two brands of insulin syringes. RESULTS: The subject had high titer anti-latex
      Ige and elevated total levels of IgE in serum. Anti-insulin IgG and IgE
      antibodies were absent. Erythema and wheals occurred at the sites of intradermal
      injection of insulin therapy components (insulin diluent and syringes) that
      contain natural latex rubber but not at the site of injection of insulin therapy
      components that do not contain natural latex rubber. CONCLUSIONS: Small
      quantities of natural latex rubber antigens in insulin injection materials can be
      sufficient to produce local cutaneous reactions at the site of insulin injection
      in individuals highly allergic to natural latex rubber.

PMID- 7587860
TI  - Self-perceived stress, hostility, and insulin resistance: lack of association.

PMID- 7587861
TI  - Grapefruit juice in alloxan-induced diabetes in rabbits.

PMID- 7587863
TI  - Accuracy of self-monitoring blood glucose meters in a high humidity, high
      temperature summer camp setting.

PMID- 7587864
TI  - Over-delivery of insulin by insulin pumps.

PMID- 7587862
TI  - Relationship of low-density lipoprotein particle size to plasma lipoproteins.

PMID- 7587865
TI  - Lipoprotein(a), apolipoprotein(a) polymorphism, and insulin treatment in type II
      diabetic patients.

PMID- 7587866
TI  - Diabetes self-management education.

PMID- 7587867
TI  - American Diabetes Association Scientific Sessions, 1995. Non-insulin-dependent
      diabetes mellitus.

PMID- 7587868
TI  - Communication and cytopathology--Part IV: Cytohistologic correlation and patient
      care.

PMID- 7587869
TI  - "Cercariform" cells: a clue to the cytodiagnosis of transitional cell origin of
      metastatic neoplasms?
AB  - The "cercariform" cell is described as a distinct cytomorphologic clue that may
      be helpful in the diagnosis of metastatic transitional cell neoplasms,
      particularly low grade. This cell has a nucleated globular body and a cytoplasmic
      process with a nontapering, flattened, bulbous or fishtail-like end. The
      cercariform cell corresponds to intermediate cells in histologic and
      ultrastructural preparations of normal urothelium. The cercariform appearance is
      the result of pseudostratification of both normal and low-grade neoplastic
      urothelium. The unique features of cercariform cells make them readily
      distinguishable from neoplastic squamous cells as well as spindle cells of
      mesenchymal origin.

PMID- 7587871
TI  - Efficacy of automated cervical cytology screening.
AB  - The Papanicolaou stained cervicovaginal smear (Pap smear) is a gynecologic
      cytologic screening tool that has dramatically reduced the incidence and
      mortality of cervical cancer. Recently, a number of problems with the Pap smear
      test, including severe cytotechnologist shortages, lack of internal quality
      controls, and high false negative rates have been emphasized by the scientific
      community and the general public. To address some of these problems, there has
      been increased development of a number of automated and semiautomated cytologic
      screening systems. A semiautomated screening system (PAPNET) was used to
      retrospectively evaluate 527 conventionally prepared Pap smears from 500
      consecutive unselected patients. This system scanned the slides and displayed 128
      of the most "abnormal" areas of each slide on a monitor. A screener reviewed
      these "abnormal" images in a blinded fashion and decided whether they represented
      variants of normal cytology, were inadequate for evaluation, or were abnormal and
      warranted manual review of the material. The screener's evaluations were then
      compared to the previously made diagnosis and discrepancies were reviewed. After
      review of the images from 500 patients, 343 (69%) were deemed to be normal
      cytology, 140 (28%) were abnormal and needed manual review, and 17 (3%) were
      inadequate. Of the 343 called normal using this system, 338 were previously
      called normal and five patients were previously diagnosed with either atypical
      squamous cells of undetermined significance (ASQUS) or low grade squamous
      intraepithelial lesions (LGSIL). Of the 140 thought to need review, 43 were
      previously diagnosed with squamous or glandular disease and 97 were previously
      diagnosed as normal. Slides from the apparent false negatives and false positives
      were again reviewed in a blinded fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587870
TI  - Neovaginal cytology after total pelvic exenteration for gynecological
      malignancies.
AB  - Vaginal reconstruction has become an established method to restore sexual
      function in women who have undergone ultraradical surgery and/or irradiation for
      the treatment of gynecologic malignancies. Cytologic evaluation of the neovagina
      serves a major role in the detection of recurrent disease. The purpose of this
      retrospective 6-yr study (January 1987-December 1993) was to evaluate the
      cytologic features of vaginal smear specimens from neovaginas constructed
      utilizing split-thickness skin grafts. Thirty-four vaginal smears were obtained
      at regular intervals from nine women (mean age: 51 yr) who underwent total pelvic
      exenteration with vaginal reconstruction for recurrent malignancies of the vagina
      and the cervix. Anucleated, keratinizing squames were a constant finding in each
      smear. Over a 4-mo-6-yr postoperative period, superficial and intermediate
      squamous cells were present in the majority of the smears and the maturation
      index showed a shift to the right. In two cases, a squamous cell carcinoma of the
      cervix recurred within the neovagina. Knowledge of the cytologic features
      associated with neovaginas is important in order to distinguish normal changes
      from neoplastic lesions.

PMID- 7587872
TI  - Significance of epithelial membrane antigen in the work-up of problematic serous
      effusions.
AB  - Differentiation of reactive and/or atypical mesothelial cells from malignant
      epithelial cells in serous effusions remains a frequent diagnostic problem. Since
      epithelial membrane antigen (EMA) positive malignant cells in serous effusions
      have been reported in almost all adenocarcinomas and most malignant
      mesotheliomas, immunoreactivity for EMA is felt to be less useful than other
      antibodies in the workup of problematic serous effusions. However, immunostaining
      of reactive and/or atypical benign mesothelial cells for EMA has not been well
      studied, with only a few series reporting either weak or negative staining for
      EMA. This study was undertaken to evaluate how often reactive and/or atypical
      appearing mesothelial cells stain positively for EMA. One hundred eighty serous
      effusions (115 pleural, 55 peritoneal, and 10 pericardial) from 123 females and
      57 males ages 20 to 89 yr were evaluated in which an antibody panel including EMA
      was performed on cell blocks (141 cases), cytospins (36 cases), or both (3
      cases). Of the 100 cytologically positive cases, EMA immunoreactivity was present
      in 97/100 (97%) cases. One EMA negative case suspicious for a metastatic renal
      cell carcinoma was lost to follow-up and not included in the analysis. The
      remaining three negative cases consisted of malignancies not expected to have EMA
      positive cells (small cell carcinoma, neuroblastoma, and synovial sarcoma).
      Therefore, EMA was positive in virtually 100% of the remaining malignant cases.
      In the 78 cytologically negative cases, EMA positivity was present in 3/78 (3.8%)
      cases. Clinical follow-up of up to 14 mo in these three cases revealed no
      evidence of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587873
TI  - Evaluation of PAPNET system for rescreening of negative cervical smears.
AB  - We rescreened 2,238 cervicovaginal smears conventionally prepared with
      Papanicolaou stain by PAPNET system. The slides screened manually as negative,
      were sent to PAPNET system. The image tapes were reviewed on a high-resolution
      monitor, and categorized as negative, unsatisfactory, and atypical. All atypical
      cases were rescreened manually. Abnormal cases were reviewed by a
      cytopathologist. Two-thousand one hundred and two (94%) cases rescreened by
      PAPNET were negative. Nine of 45 unsatisfactory cases by PAPNET were
      unsatisfactory by manual review. Ninety-one (4.0%) cases by PAPNET were atypical.
      On manual rescreening, 86 of 91 were negative, 20% showing benign cellular
      changes; five of 91 were atypical, the atypia, however, not exceeding low-grade
      category. The detection rate by PAPNET method was 0.2% (five of 2,238 cases). We
      conclude: 1) In a cytology laboratory with good quality control, PAPNET
      rescreening does not significantly increase the detection rate. 2) For cytology
      laboratories without in-house rescreening, PAPNET offers an alternative at a
      price. 3) The PAPNET system also offers a tool by which a laboratory can
      occasionally monitor its performance. 4) The cost benefit analysis of the system
      requires further study and scrutiny.

PMID- 7587876
TI  - Paracoccidioidomycosis: diagnosis by fine-needle aspiration cytology.
AB  - A 4-yr-old girl presented with constitutional symptoms, abdominal swelling,
      ascites, and cervical lymphadenopathy. Fine-needle aspirate smears of a cervical
      lymph node revealed numerous round yeasts, many of them with several peripheral
      buds fitting the pattern of Paracoccidiodes brasilensis. This appears to be the
      first case in which the diagnosis of this deep mycosis was achieved by FNAC. The
      procedure may prove useful for rapid diagnosis in cases like the present one
      which represents the so-called acute disseminated form which affects mainly
      children and immunosuppressed patients and can be rapidly fatal.

PMID- 7587875
TI  - Cytopathology of undifferentiated (embryonal) sarcoma of the liver.
AB  - We have studied one undifferentiated (embryonal) sarcoma of the liver (USL) by
      fine-needle aspiration cytology (FNAC) and have correlated the cytologic findings
      with those seen in the histologic sections. The main cytologic and
      immunocytochemical features were: cellular aspirates, mesenchymal clusters,
      disparity in individual cell size (small round cells, and multinucleated giant
      cells, sometimes bizarre), absence of biliary pigment, AFP-negative and vimentin
      negative tumor cells, AFP-negative and PAS-positive hyaline globules, and
      apoptotic cells. Only immunostaining for alpha-1-antitrypsin, alpha-1
      antichymotrypsin, and carcinoembryonic antigen were positive in tumor cells in
      histologic sections. The differential diagnosis should be carried out with
      rhabdomyosarcomas, hepatoblastomas, malignant fibrous histiocytomas, and poorly
      differentiated hepatocarcinomas. We think that the cytologic features observed in
      this case, evaluated both in the appropriate clinical context and in the light of
      the laboratory findings, may permit the correct diagnosis of this infrequent
      liver tumor. Nevertheless, more cases need to be studied to assess the
      reliability of our findings.

PMID- 7587874
TI  - Primary and metastatic high-grade carcinomas of the salivary glands: a cytologic
      histologic correlation study of twenty cases.
AB  - We reviewed the clinical and fine-needle aspiration (FNA) findings in 20 patients
      with poorly differentiated carcinomas presenting initially as parotid or as
      submandibular masses. There were 11 primary tumors and nine metastatic
      malignancies in 14 males and six females ranging in age from 39 to 89 yr (median
      = 66). The tumor types included three primary carcinomas with oncocytic features,
      three additional cases of high-grade parotid carcinoma, one case of primary
      neuroendocrine carcinoma, two examples of malignant mixed tumor, one high-grade
      mucoepidermoid carcinoma, and a single example of malignant lymphoepithelial
      lesion. Six patients with metastatic carcinoma had previous diagnoses of
      malignancy. In the three remaining individuals, primary carcinomas of the lung
      (two cases), and an unknown primary site presented initially as parotid masses.
      Five examples of metastatic squamous cell carcinoma, one metastatic basal cell
      carcinoma, and two metastatic renal cell carcinomas were identified. One parotid
      lymphoepithelioma was interpreted cytologically as an atypical
      lymphoproliferative process suggestive of Hodgkin's disease. Nineteen cases (95%)
      were correctly classified as carcinoma at the time of FNA. High-grade carcinomas
      aspirated from the parotid may be primary, but are frequently metastatic to
      either the gland, or to an intraparotid lymph node. Our experience indicates that
      some metastatic carcinomas present at this site, without a previous history of
      malignancy. Distinguishing primary from metastatic lesions has important
      therapeutic implications.

PMID- 7587877
TI  - Epithelioid hemangioendothelioma of the lung: pleural effusion cytology,
      ultrastructure, and brief literature review.
AB  - Epithelioid hemangioendothelioma (EHE) of the lung is a low-grade malignant tumor
      of vascular origin initially described under the name intravascular
      bronchioloalveolar tumor (IVBAT). We present a case of a 44-yr-old Caucasian
      female with severe radiating back pain, shortness of breath, recurrent malignant
      pleural effusions, and a negative malignancy workup. Cytopathologic examination
      of the four pleural fluid specimens revealed large undifferentiated plasmacytoid
      malignant cells with abundant pink and finely granular cytoplasm, round nuclei,
      and prominent nucleoli. The differential diagnosis based on the cytologic
      findings included hepatocellular, adrenal, and renal carcinomas, melanoma,
      mesothelioma, and neuroendocrine tumors. Electron microscopy performed on a
      pleural fluid specimen and subsequent histologic examination of pleural and lung
      biopsies established the diagnosis of EHE.

PMID- 7587879
TI  - Multilocular renal cyst: a diagnostic pitfall on fine-needle aspiration cytology:
      case report.
AB  - Benign renal lesions, apart from simple cysts, are rarely sampled by fine-needle
      aspiration biopsy (FNAB) and are potential diagnostic pitfalls. A complex renal
      mass in a 33-yr-old pregnant woman, presenting in the second trimester with
      haematuria, was aspirated twice, a week apart, under ultrasound guidance. The
      second FNAB yielded predominantly mesenchymal elements thought to represent an
      angiomyolipoma, but the mass was identified as a multilocular renal cyst (MLRC)
      on the nephrectomy specimen. Differential diagnoses of angiomyolipoma, MLRC, and
      renal cell carcinoma (RCC) are compared and discussed in relation to patient
      management.

PMID- 7587880
TI  - Application of immunostaining for muscle specific actin in detection of
      myoepithelial cells in breast fine-needle aspirates.
AB  - Myoepithelial cells play an important role in the interpretation of breast fine
      needle aspiration biopsy, since these cells are believed to be a component of a
      benign process in breast lesions. Myoepithelial cells are usually easy to
      recognize, however, other cells can morphologically simulate myoepithelial cells
      and make the distinction difficult. To assess the feasibility of immunostaining
      as an adjunct to identify myoepithelial cells, we have used immunocytochemistry
      using monoclonal antibody against muscle specific actin (MSA) in our breast fine
      needle aspirates. Herein, we report our experience in immunocytochemical
      detection of myoepithelial cells using labeled Streptavidin Biotin Detection
      System on destained Papanicolaou stained smears and cell block preparations
      obtained from breast aspirates.

PMID- 7587878
TI  - Undifferentiated small-cell carcinoma of the urinary bladder: report of two cases
      with a primary urinary cytodiagnosis.
AB  - Two undifferentiated small-cell carcinomas of the urinary bladder are reported.
      The patients, 68- and 55-yr-old men, respectively, presented with painless
      hematuria. In the first case, numerous small, lymphocyte-like cells with coarse
      chromatin, sometimes with small nucleoli, and high nuclear/cytoplasmatic ratios
      were found in cytologic urine specimens. A cytodiagnosis of undifferentiated
      small-cell cancer was made. In the second case, urine samples showed rare
      aggregates of small, undifferentiated cells in association with malignant
      urothelial cells. The cytodiagnosis of mixed tumor composed of undifferentiated
      small cell and transitional carcinoma was confirmed by histologic examination.
      The presence of focal reactivity with anti-chromogranin antibody and
      neurosecretory granules via electron microscopy supports a neuroendocrine
      differentiation for the small neoplastic cells. The patients died 13 and 8 mo
      after diagnosis, respectively.

PMID- 7587882
TI  - HPV detection in cytological cases with condylomatous or dysplastic changes: a
      study with PCR and in situ hybridization on cytological material.
AB  - Cytobrush samples of 80 patients, who previously had a cytological or
      histopathological diagnosis of condyloma and/or dysplasia were investigated for
      human papillomavirus infection (HPV) by polymerase chain reaction (PCR) and in
      situ DNA hybridization technique (ISH). The results were compared with
      concomitantly obtained cytological Pap-stained smears or, in some cases,
      histological sections. The time between the diagnosis of the original and the
      concomitant cytology/histopathology was less than 1 yr. Six additional patients
      had similar morphological diagnoses 2-4 yr before. Five more cases were included
      on clinical diagnosis of HPV. Compared with the original morphological diagnoses,
      70% of the cases were positive by PCR and/or ISH. The concomitant morphology was
      not diagnostic of HPV in 44 out of 80 cases (55%), showing a relatively high
      percentage of cases morphologically normalized in the interval since the first
      specimen was taken. After detection with PCR, 30 cases (37.5%) were negative for
      HPV. Only one of the patients with a previous disease 2-4 yr before was HPV
      positive by PCR and two out of five patients with a clinical diagnosis of HPV.
      ISH could be performed on 67/80 cases, 43 of which were positive for HPV. There
      was a good agreement between the results of ISH and PCR, but there were six cases
      positive by ISH and negative by PCR. In these cases, few infected cells may have
      escaped detection by PCR. Both methods seem to be able to detect silent HPV
      infections and comparison with concomitant cytology/histopathology shows that
      morphology alone is insufficient for HPV detection in these cases.

PMID- 7587883
TI  - Standards and the law.

PMID- 7587881
TI  - Radiation treatment effects in cervical cytology.

PMID- 7587884
TI  - A modest proposal for diagnostic restraint.

PMID- 7587885
TI  - Malignant melanoma of soft parts diagnosed by needle aspiration cytology and
      electron microscopy.

PMID- 7587887
TI  - [Apoptosis of tumor cells in lectin-dependent lymphokine-activated killer cell
      mediated cytotoxicity].
AB  - By using DNA electrophoresis and propidium iodide (PI) staining flow cytometry
      (FACS) analysis, we studied the mechanisms of lymphokine-activated killer (LAK)
      cell-mediated cytotoxicity. In the presence of pokeweed mitogen (PWM), human LAK
      cells induced DNA fragmentation of two leukemic cell lines (U937 cells and Raji
      cells) and two solid tumor cell lines (SW1116 cells and Hep-2 cells), a hallmark
      of apoptosis. The reactions were carried out at the effector/target ratio of 1:1
      and in 4 hr coculture. Pretreatment with RNA and protein synthesis inhibitors
      (actinomycin D and cycloheximide) did not prevent the target cells from
      apoptosis. As the TNF-resistant tumor cell lines such as SW1116 cells and Raji
      cells were also triggered to apoptosis, other factors than TNF would play the
      role. DNA-PI staining FACS analysis also suggested that a part of LAK cells
      underwent apoptosis to some extent during incubation with target cells. The
      results provide a new way to investigate the mechanisms of cytotoxicity of LAK
      cells and to enhance the efficacy of adoptive tumor therapy with LAK cells.

PMID- 7587886
TI  - Polycystic kidney disease: etiology, pathogenesis, and treatment.
AB  - Once viewed as hopelessly incurable disorders and the dustbin for careers in
      academic medicine, the polycystic kidney diseases have emerged as prime targets
      of pathophysiologic study and palliative and definitive treatment in the era of
      molecular medicine. Polycystic kidney disease (PKD) may be hereditary or
      acquired. The major inherited types are autosomal dominant (AD) and autosomal
      recessive (AR). ADPKD is caused by at least two (and possibly three) genes
      located on separate chromosomes, while ADPKD-1 is due to a 14 kb transcript in a
      duplicated region on the short arm of chromosome 16 very near the alpha-globin
      gene cluster and the gene for one form of tuberous sclerosis. ADPKD-2 has been
      assigned to the long arm of chromosome 4. ARPKD is due to a mutated gene on both
      copies of the long arm of chromosome 6. Cysts originate in renal tubules.
      Proliferation of tubule epithelial cells modulated by endocrine, paracrine, and
      autocrine factors is a major element in the pathogenesis of renal cystic
      diseases. In addition, fluid that is abnormally accumulated within the cysts is
      derived from glomerular filtrate and, to a greater extent, by transepithelial
      fluid secretion. Abnormal synthesis and degradation of matrix components
      associated with interstitial inflammation are additional features in the
      pathogenesis of renal cystic diseases. The ADPKD genotypes are characterized by
      bilateral kidney cysts, hypertension, hematuria, renal infection, stones, and
      renal insufficiency. ADPKD is a systemic disorder; cysts appear with decreasing
      frequency in the kidneys, liver, pancreas, brain, spleen, ovaries, and testis.
      Cardiac valvular disorders, abdominal and inguinal hernias, and aneurysms of
      cerebral and coronary arteries and aorta are also associated with ADPKD.
      Treatment is supportive: dietary regulation of salt and protein intake, control
      of hypertension and renal stones, and dialysis and transplantation at the end
      stage. ARPKD is a relatively rare disease that causes clinical symptoms at birth,
      with significant mortality in the first month of life. The cysts develop
      primarily in the collecting ducts because of a failure in the maturation process.
      Early complications include Potter's syndrome; excessive size of the kidneys,
      causing respiratory dysfunction; hypertension; and renal insufficiency. Hepatic
      fibrosis is an associated extrarenal problem that results in significant
      morbidity in young children and adolescents. Treatment includes supportive care,
      dialysis, and renal transplantation. Acquired cysts (solitary/simple) are
      commonplace in older persons. Multiple cysts may be seen in association with
      potassium deficiency, congenital disorders, metabolic diseases, and toxic renal
      injury.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7587888
TI  - [Correlation studies on the alterations of multiple tumor suppressor genes in
      human esophageal cancer and in human and monkey esophageal epithelial cells
      treated with N-methyl-N-benzyl nitrosamine].
AB  - The correlation between the mutation spectra of tumor suppressor genes Rb, p53,
      APC and MCC in human esophageal cancer (EC) and in human and monkey esophageal
      epithelium treated with N-Methyl-N-Benzyl nitrosamine (NMBzA) was studied using
      PCR amplification and direct sequencing methods. The results showed that in 40.9%
      (9/22) of the specimen examined, the mutation spectrum of p53 in primary EC was
      similar to that in the esophageal epithelium of human fetus (in vitro) and monkey
      (in vivo) treated with NMBzA. The same mutational spectra of tumor suppressor
      genes Rb, APC, MCC in esophageal epithelium cells of human and monkey treated
      with NMBzA were also found in some human primary EC. The correlation observed in
      the mutation spectra of multiple tumor suppressor genes between human primary EC
      and the esophageal epithelia of human and monkey origin treated with NMBzA
      wouldsuggest that NMBzA may be the esophageal etiological agent for human
      esophageal cancer in China.

PMID- 7587890
TI  - [Cloning of anti-breast cancer monoclonal antibodies from phage antibody
      libraries].
AB  - Rodent monoclonal antibodies (McAbs) with anti-tumor specificity can be isolated
      from hybridomas by screening reactivity against tumor cells. Here, as an approach
      to bypass hybridoma technology, we attempted to isolate anti-tumor rodent McAbs
      directly from phage antibody libraries. We first used RT-PCR reactions to amplify
      diverse repertoires of heavy (Fd part) and light chains from spleen lymphocytes
      of Balb/c mice immunized with human cancer cell line BCap37 and then, by
      recombination of the repertoires in bacteria, generated a repertoire (1.0 x
      10(7)) of Fab fragments displayed on filamentous phage. Four rounds of selection
      against living cancer cells showed specific enrichment of phage antibodies. After
      the fourth round of selection 174 out of 182 clones exhibited cancer cell binding
      capacity. The specificity of those clones was verified by reactivity against 12
      human tumor cell lines, human lymphocytes and fibroblasts. In the production of
      monoclonal antibodies toward human cancer, this strategy may provide an
      alternative approach, and even surpass the hybridoma technology.

PMID- 7587889
TI  - [Studies on the cell models of differentiation reversal phenotypes of human
      rhabdomyosarcoma].
AB  - We have observed the features of malignant phenotypes in human rhabdomyosarcoma
      RD cells. These cells exhibited high growth rate, aberrant relation between cell
      proliferation and myogenic terminal differentiation, blockage of
      myofibrillogenesis, inhibition of gap junctional intercellular communication
      (GJIC) and inhibition of transcriptional expression of gap junction gene,
      connexin 43 (Cx43). By utilization of single cell subclone separation and cDNA
      cell transfection techniques, we obtained several RD subclones, among them 3 were
      representative of differences in phenotypes and were selected for further study.
      They were single-cell subclone RDL6, RDL3, and a Cx43 transfectant clone of RDL6,
      the RDL6/C-4. Through determination of cell growth doubling time, co-stain of 3H
      TdR autoradiography with myosin heavy chain (MHC) immunofluorescence,
      immunofluorescent cytochemical examination and slot-blot analysis, it was
      demonstrated that significant differences existed between each of the 3
      subclones. They were differnet in cell growth rate, cell proliferation and
      terminal differentiation coupling relation, progress of myogenesis, functional
      expression of Cx43 gene, and expression of proto-oncogenes, c-myc, Ha-ras and c
      met products, therefore they could be used as cell models in the study of reverse
      transformation of rhabdomyosarcomas. The reversal differentiation markers, their
      examination approaches and practical value were discussed.

PMID- 7587891
TI  - [Correlation study of allelic gene deletion of nm23-H1 and human colorectal
      carcinoma metastasis].
AB  - In recent years, a tumor suppressor gene nm23 has been found to be associated
      with decreased tumor metastatic potential. Allelic deletion, mutation and low
      expression of this gene has been correlated with tumor metastatic potential in a
      number of tumors. There are two known isotypes of human nm23 gene, named nm23-H1
      and nm23-H2. We examined DNA from 23 cases of colorectal carcinomas and their
      corresponding normal mucosa using Southern blot hybridization with nm23-H1 cDNA
      probe. Five cases with allelic deletion of nm23-H1 gene were found, with allelic
      deletion rate of 57. 1% (4/7) in cases with metastasis to lymph node, liver or
      other organs, and 6.2% (1/16) in cases without metastases (P < 0.005). There is
      no correlation between allelic deletion and tumor size, location or
      differentiation. This result indicates that nm23-H1 gene plays an important role
      in the metastasis of colorectal carcinoma.

PMID- 7587893
TI  - [Growth promoting effect of IL-6 on medulloblastoma cells in vitro].
AB  - Expression of IL-6 and IL-6 signal transducer genes (IL-6R and gp130) in human
      medulloblastoma cells were investigated by Northern blot analysis, RT/PCR and
      immunocytochemical staining. The results revealed that among 13 tumor cases and 3
      established medulloblastoma cell lines, 95% of them were found to express full
      set of IL-6 signal transducer genes, IL-6R and gp 130, but none of them expressed
      IL-6. Incubation of medulloblastoma cells in vitro with recombinant IL-6 could
      apparently stimulate cell growth and enhance DNA synthesis. Our data thus for the
      first time demonstrate that though IL-6 is not expressed by medulloblastoma cells
      themselves, IL-6 can act on medulloblastoma cells through its signal transducers
      by a paracrine pathway. Since medulloblastomas are surrounded by gliosis and
      infiltrated by immune activated cells which are known to express IL-6, the
      influence of those IL-6 producing cells on the development and progression of
      medulloblastomas should be taken into account.

PMID- 7587892
TI  - [Experimental study on the treatment of human hepatocellular carcinoma by
      fibroblast-mediated human IFN-alpha gene therapy in combination with adoptive
      chemoimmunotherapy].
AB  - In the present study, we observed the therapeutic effect of the fibroblast
      mediated human IFN alpha gene therapy in combination with IL-2/AK/DOX adoptive
      chemoimmunotherapy on human hepatocellular carcinoma-bearing nude mice. Activated
      killer cells (AK) were prepared from human peripheral mononuclear cells co
      stimulated in vitro with IL-2 and inactivated human hepatocellular carcinoma SMMC
      7721 cells. The results demonstrated that (1) When the NIH3T3-IFN-alpha+ cells
      were implanted i.p. to the tumor-bearing nude mice, the growth of tumor was
      inhibited and the survival time of the mice was prolonged; (2) The growth of
      tumor was significantly inhibited when AK was injected i.v. and IL-2 was injected
      i.p. after the NIH3T3-IFN-alpha+ cells had been implanted; (3) The best
      therapeutic results could be achieved when NIH3T3-IFN-alpha+ cells were used in
      combination with IL-2/AK/DOX. All these results suggeste that the fibroblast
      mediated human IFN-alpha gene therapy could be used to treat human hepatocellular
      carcinoma but better results can be obtained when used in combination with IL-2
      based immunotherapy.

PMID- 7587894
TI  - [Effect of Achyranthes bidentata polysaccharides (ABP) on antitumor activity and
      immune function of S180-bearing mice].
AB  - Achyranthes bidentata polysaccharides (ABP), extracted from the root of
      Achyranthes bidentata Blume, 25-100mg.kg-1.d-1 x 7 could inhibit tumor growth by
      31%-40%. Combination of cyclophosphamide (Cy) and ABP increased the rate of tumor
      growth inhibition to 58%. ABP 50 and 100% mg/kg ip could potentiate LAK cell
      activity and increase the Con A (5 micrograms/ml)-induced production of tumor
      necrosis factor (TNF-beta) from murine splenocytes. The optimal time for TNF
      production was on d 8. We also found that ABP 1-2 micrograms/ml strongly
      inhibited the proliferation of S180 and K562 cells in vitro. The S180 cell
      membrane content of sialic acid was increased and phospholipid decreased after
      ABP acting on cells for 24 hours. The changes were significantly different from
      the control group (P < 0.05 or P < 0.01), but the membrane cholesterol content
      and membrane mobility indices (Ch/PI) were not affected. The results suggest that
      the antitumor mechanism of ABP may be related to potentiation of the host
      immunosurveillance mechanism and the changes in cell membrane features.

PMID- 7587896
TI  - [A clinical trial Furlutal in the prevention of anorexia, weight loss and
      myelosuppression due to chemotherapy].
AB  - From October, 1993 to September, 1994 a controlled clinical trial was conducted
      in 60 patients on Furlutal in the prevention of anorexia, weight loss and
      myelosuppression caused by chemotherapy. Patients were randomly divieded into
      three groups, they received Furlutal in the 1st (group A), 2nd (group B) and
      every cycle in (group C), respectively. The results show that Furlutal is
      effective in preventing anorexia, weight loss and myelosuppression. In group A,
      85% patients gained weight, averaged 2.5kg (range: 1-7kg); 80% in group B,
      averged 2.25kg (1-7kg) and 95% in group C, averaged 4kg (2.5-8kg). Grade III
      myelosuppression, according to WHO criteria, 52.5% occurred in of patients
      treated with 80 cycles of chemotherapy only while it occurred in 19% in those
      treated with 100 cycles of chemotherapy plus Furlutal (P < 0.01).

PMID- 7587895
TI  - [Mutation of P53 gene in a highly metastatic human lung cancer cell line].
AB  - PG cell line, derived from a lung giant cell carcinoma, has the characteristics
      of rapid growth and high tumorigenicity. When transplanted to nude mice,
      spontanious metastasis to lung and lymphnode is high in frequency and stable. To
      understand the molecular basis of PG's biological behaviors, expression of tumor
      suppressor gene p53 was studied. It was found that expression of p53 protein was
      increased as demonstrated by immunohistochemical stainning. A change in
      polymorphsim in exon 7 of p53 gene was detected by nonisotopic PCR-SSCP,
      suggesting a change in base composition. Thermal cycling sequencing of both
      strands of exon 7 demonstrated a transversion of CGG to CTT at codon 248. Similar
      study with the same methods on Ki-ras oncogene was done, but no mutation was
      found. The relationship between p53 gene mutation and the metastatic potential of
      PG cells needs further exploration.

PMID- 7587897
TI  - [Expression and clinical significance of the AgNOR and PCNA in Barrett's
      adenocarcinoma and its precancerous lesions].
AB  - In order to investigate the expression of AgNOR and PCNA in malignant Barrett's
      esophagus and benign Barrett's esophagus with or without dysplasia, 50 specimens
      and biopsies were examined using silver-staining and immunohistochemical methods.
      The results showed that the expression of AgNOR and PCNA in malignant Barrett's
      esophagus were higher than those in benign Barrett's esophagus with dysplasia,
      which were in turn higher than those in benign Barrett's esophagus without
      dysplasia. The difference between malignant group and other groups was
      significant. The results suggest that AgNOR and PCNA may be useful as an adjunct
      in screening patients with Barrett's esophagus for early malignant change,
      especially in high-grade dysplasia group.

PMID- 7587898
TI  - [Imaging diagnosis of carcinoma of the ampulla of Vater].
AB  - Ten patients with carcinoma of the ampulla of Vater were reviewed with both
      ultrasonography (US), CT scans (n = 10), and hypotonic double contrast duodenum
      examination (n = 5). Tumor was shown by US as abrupt obstruction of distal common
      bile duct (n = 6), a small mass well-delineated within the dilated distal common
      bile duct (CBD) (n = 4). The second part of duodenum was depicted clearly in CT
      scan without enhancement, and a small filling defect could be revealed at the
      inner surface in 5 cases, as well as an abrupt obstruction of distal CBD, local
      mass was shown in 4 cases. Enhancement of tumor manifested as local mass and/or
      ductal wall thickening after iv contrast administration was shown in 3 cases. One
      case with local lymph node enlargement (25 mm) was revealed by US as well as CT.
      Non-resectability is implicated by the ill-defined contour of tumor mass and/or
      portal vein, superior mesenteric artery and vein, but resectability cannot be
      excluded by displacement and distortion of these vessels with clear delineation.
      Detectability of lymph node smaller than 10 mm and evaluation of T, N staging are
      limited by imaging examination. Local filling defect and irregularity of mucous
      membrane of duodenum were revealed in 4 cases by hypotonic double contrast
      examination.

PMID- 7587899
TI  - [Evaluation of missing diagnosis of metastatic lymph node in gastric cancer].
AB  - The missing diagnosis rate of metastatic lymph nodes in 38 cases of radical
      gastrectomy specimens by methylene blue staining and serial histologic section
      was evaluated as compared to that by routine examination of one histologic slide
      of palpable enlarged lympy nodes. The results showed that after 1251 lymph nodes
      had been picked up by palpation method, 1004 additional minute lymph nodes were
      dissected out following methylene blue staining with an average of 59.3 lymph
      nodes in each case. The methylene blue-stained lymph nodes accounted for 44.5% of
      the total lymph nodes, in which 32 were found to have metastasis which accounted
      for 13.8% of metastatic lymph nodes. The 2046 metastasis negative lymph nodes
      according to routine histologic examination were then serially sectioned at 45
      microns distance and 25 sections were observed for each lymph node specimen.
      Minute metastatic foci were found in 23 lymph nodes, accounting for 9.9% of the
      metastatic lymph nodes. Therefore, 23.7% metastatic lymph nodes escaped detection
      by the routinely used histologic examination.

PMID- 7587900
TI  - [The role of ondansetron (Qilu) in the prevention of non-cisplatin-induced
      vomiting--a randomized clinical trial].
AB  - The antiemetic effect of ondansetron (supplied by Qilu Pharmaceutical Company) in
      patients receiving non-cisplatin chemotherapy (containing CTX and/or ADM) was
      studied in a multiple centre, randomized cross-over trial. The patients who had
      vomiting in the first turn of chemotherapy entered the trial. The patients
      received randomly ondansetron or control drugs-metoclopramide or Zofran (Glaxo)
      in the second turn of chemotherapy. In the third, the patients were cross-over to
      use the other antiemetic drug. A total of 155 patients were enrolled into the
      study. The results showed, the effective control rate (0-2 emetic episodes) on
      the first day were 87.7% of patients treated with ondansetron and 61.6% treated
      with metoclopramide. The mean frequency of vomiting was 0.8 times in ondansetron
      and 2.7 times in metoclopramide (P < 0.01). Ondansetron was superior to
      metoclopramide for the control of emesis. The antiemetic effects of ondansetron
      (Qilu) and Zofran (Glaxo) were very similar. The side-effects of ondansetron were
      mild.

PMID- 7587901
TI  - [Whole organ subserial section examination of occult breast carcinoma].
AB  - In mastectomy specimens, the primary foci of occult breast carcinoma were
      examinated usually by routine histopathological method, but the result was not
      satisfactory. The detecting rates of primary foci were 50%-56% in China and 45%
      75% in some other countries. In this study, whole organ subserial section was
      performed in 20 cases of occult breast cancer from April, 1988 to February, 1994.
      Primary foci were found in 16 cases (80%) by microscopic examination. Diameters
      of 10 foci were less than 1.0cm and the smallest one was 0.3 x 0.1 x 0.1cm. In
      addition, occult breast cancer with multiple foci was detected in 5 cases
      (31.25%), which would be very difficult to be found by routine histopathological
      examination. The possible causes for the failure of detection of the primary foci
      on whole organ section are discussed.

PMID- 7587903
TI  - [Distribution of androgen receptor in primary liver cancer and its clinical
      significance].
AB  - A method of receptor binding assay (RBA) was adopted to measure the distribution
      of androgen receptor (AR) in liver cancer and tissue in its vicinity in 63
      patients with primary liver cancer undergone laparotomy and in non-tumor liver
      tissue in 7 cases with gastric carcinoma. The results showed (1) AR was
      demonstrated in the liver cancer tissue and surrounding non-tumorous tissue, and
      the non-tumor liver tissue. The content of AR in the nucleus was significantly
      higher than that in the cytoplasm. (2) There was no difference in the amount of
      AR between the tumor tissue and tissue surrounding it. The expression of AR in
      the liver cancer tissue or the surrounding tissue was more marked than that in
      the non-tumor tissue. (3) Expression of AR in the tumor tissue seemed to
      correlate with more frequent tumor recurrence one year after radical resection.

PMID- 7587904
TI  - [Disease-free survival of acute leukemia patients receiving autologous bone
      marrow transplant following intensive chemotherapy--a report of 11 cases].
AB  - Eleven cases of acute leukemia patients were treated with autologous bone marrow
      transplantation (ABMT) following intensive chemotherapy with TACC protocol. Among
      them, eight were in first remission, three in second remission. The median age
      was 38 years (24-45 years). Bone marrow was purged in vitro before
      transplantation with procaine and hyperthermia in three cases with acute
      promyelocytic leukemia. In all patients, ABMT was successful. The results of
      treatment are as follows: as of May, 1994, the median remission and disease-free
      survival period was 31 months (6-57), seven cases have been in complete remission
      for 6-57 months (median 42 months) after treatment and are still alive. In four
      cases, ABMT was complicated by infection but it was controlled by antibiotics.

PMID- 7587902
TI  - [Clinical study on the feasibility of preserving vagal trunks in the surgical
      treatment of carcinoma of the thoracic esophagus].
AB  - The results of preserving vagal trunks in the surgical treatment of 47 patients
      with the carcinoma of the thoracic esophagus were discussed through a controlled
      study. There were 20 patients in the test group with vagus nerve being preserved
      (PG) and 27 in the control group (CG) with vagus nerve being routinely severed.
      Eighteen patients in PG and 26 in CG underwent radical resections, the remaining
      patients received palliative surgery. Pathological findings showed that 3 cases
      (15.0%) in PG and 3 cases (11.1%) in CG had cancerous invasion near the vagal
      trunks and/or their main branchs close to the primary cancer; and 1 case (5.0%)
      in PG and 3 (11.1%) in CG the vagal nerves were actually invaded by cancer cells.
      Determinations of basal gastric acid output (BAO) and half gastric emptying time
      (T 1/2) revealed that the mean value of BAO (1.93mmol/h) and T 1/2(63.51min.) of
      the PG were statistically different from those of 0.75mmol/h and > 105min. in CG,
      but similar to those of the healthy group and the preoperative control values. We
      consider that it is feasible to preserve vagal trunks in the operation and is
      beneficial in minimizing of postoperative disturbances of gastric acid output and
      gastric motility; but the indications of this procedure should only be limited to
      T1-T2 lesions in order not to jeopardize the radicality of tumor resection.

PMID- 7587905
TI  - [Primary tumour of the trachea with a report of 24 cases].
AB  - Twenty-four cases of primary tumour of trachea are reported in this article. In
      the 23 operated cases, 19 received curative excision (82.6%) and 4 cases
      palliative excision with tracheostomy. In these 24 cases, 21 cases were malignant
      and 3 cases benign. Tumour located at upper trachea in 8 cases, at median trachea
      in 6 cases and at lower trachea in 10 cases. The 19 operated patients all
      recovered. The survival rates in 1, 3, 5 and 10 years were 82.3% (14/17), 75%
      (9/12), 75% (6/8) and 50% (2/4), respectively. The authors suggested that early
      diagnosis should be paid more attention because misdiagnosis rate was high. The
      operation condition and procedures are discussed.

PMID- 7587906
TI  - [VM-26 plus CCNU in the prevention of brain metastasis in lung cancer patients].
AB  - Brain metastasis is of frequent occurrence in patients with cancer of the lung.
      To ascertain if brain metastasis is preventable, 34 lung cancer patients without
      brain metastasis were treated with 4 cycles of VM-26 plus CCNU at 4-week
      intervals. As a control for comparison, an equal number of lung cancer patients
      free of brain metastasis were treated with chemotherapy protocol which did not
      include VM-26 and CCNU. The patients were monitored by clinical symptoms, signs
      and CT or MRI scan and were followed up for 4-12 months. The results indicate
      that none of the VM-26 plus CCNU-treated patients developed brain metastasis
      while brain metastasis occurred in 7 (20.5%) of 34 control patients. The
      difference was statistically significant (P < 0.05).

PMID- 7587908
TI  - Effects of insulin therapy upon plasma lipid fatty acids and platelet aggregation
      in NIDDM with secondary failure to oral antidiabetic agents.
AB  - The effects of intensive insulin therapy on metabolic control, fatty acid
      metabolism and platelet function were studied in 18 non-obese non-insulin
      dependent diabetics (NIDDs) with secondary failure to oral antidiabetic drugs
      (OAD). Patients were randomly allocated either to continue maximal OAD (Group I,
      n = 9) or to receive a multiple injection regimen of insulin therapy (Group II, n
      = 9) for a 6-month period. At baseline both groups were identical for clinical
      and biological parameters. At study day 180, fasting blood glucose (P < 0.01) and
      mean capillary blood glucose (P < 0.05) were reduced in group II but the
      difference between HbA1 percentages remained non-significant. At study day 60, in
      total plasma lipids, oleic acid was lower (P < 0.05), linoleic acid (P < 0.05)
      and the sum of polunsaturated fatty acids (PUFA) (P < 0.05) were higher in group
      II than I. In triglycerides, palmitic acid was lower in group II at study days 60
      (P < 0.01) and 180 (P < 0.05), whereas gamma-linolenic acid was decreased (P <
      0.05) at study day 180 only. A similar change was noted in cholesterol esters for
      gamma-linolenic acid at study day 60 (P < 0.05). No difference was noted between
      both groups for platelet agregation, insulin sensitivity and clinical parameters
      despite a significant increase in body weight in group II at study day 180.
      Positive correlations were obtained between the content of different lipid
      fractions in some PUFA and the glucose clearance. We conclude that optimized
      insulin therapy in NIDDs with secondary failure to OAD leads to a transient
      improvement in glucidic and lipidic metabolism but has no significant effect upon
      platelet aggregation and insulin sensitivity.

PMID- 7587909
TI  - The use of orthotic devices to correct plantar callus in people with diabetes.
AB  - Foot problems are a major cause of morbidity in people with diabetes. Plantar
      callus is common and is a sign of abnormal foot pressures. Shear stresses at
      these areas of high foot pressures may ultimately result in ulcer formation. This
      study compared the effect on plantar callus of the use of rigid orthotic devices
      and conventional podiatric care. Twenty diabetic subjects participated in the
      study and were randomly allocated to conventional treatment (n = 11) or orthotic
      device treatment (n = 9). After 12 months the patients in the orthotic group
      showed a significant reduction in callus grade, whereas the conventionally
      treated group showed no significant change. There were no adverse effects from
      wearing the orthotic device. Rigid orthoses have a beneficial effect on plantar
      callus presumably through the lowering and redistribution of abnormal foot
      pressures.

PMID- 7587910
TI  - Long-term effect of eicosapentaenoic acid ethyl (EPA-E) on albuminuria of non
      insulin dependent diabetic patients.
AB  - Dietary cod-liver oil containing eicosapentaenoic acid is effective on
      microvascular albumin leakage in diabetic patients with albuminuria. We
      determined the long-term effects of oral pure eicosapentaenoic acid ethyl (EPA-E:
      900 mg/day) administration on diabetic nephropathy in non-insulin dependent
      diabetic (NIDDM) patients. The effects of EPA-E were determined by observing the
      changes of the index of urine albumin excretion level/urine creatinine (Cr)
      excretion level (UAI), the ratio of beta 2-microglobulin excretion level/urine Cr
      excretion level (beta 2-MG/Cr) and the ratio of N-acetyl-D-glucosaminidase
      excretion level/urine Cr excretion level (NAG/Cr) at 3, 6 and 12 months after the
      start of the treatment. Oral EPA-E administration immediately improved the
      increased UAI at 3 months after the start of treatment. A significant improvement
      of the UAI by EPA-E was sustained 12 months later. EPA E administration also
      tended to decrease the urine beta 2-MG/Cr ratio from 6 months, but the difference
      was statistically not significant. However, the urine NAG/Cr ratio was not
      changed by EPA-E administration. EPA-E administration did not affect blood
      pressure levels, glycemic control and lipid metabolism in these patients. The
      present data indicated that EPA-E administration improved increased albumin
      excretion in NIDDM patients with nephropathy and its effects on albuminuria
      sustained for at least 12 months after the start of treatment. However, tubular
      factors were not influenced by EPA-E administration.

PMID- 7587912
TI  - Excess maternal history of diabetes in Caucasian and Afro-origin non-insulin
      dependent diabetic patients suggests dominant maternal factors in disease
      transmission.
AB  - We examined the records of 2576 patients with non-insulin-dependent diabetes
      mellitus (NIDDM) and categorised them according to race and family history of
      diabetes. Family history of diabetes is known to play an important role in the
      development of NIDDM, and a maternal history is thought to be most influential.
      We found that a maternal history of diabetes was present in 60% of Caucasian and
      West Indian patients with a parental history of diabetes, whereas in Asian
      patients the figure was only 34%. Asian men were also more likely to have a
      father with diabetes. This anomaly may be due to cultural differences in the
      reporting of the disease. Our data support the dominant maternal role in the
      development of NIDDM in their offspring and suggest an under-reporting of NIDDM
      in Asian females.

PMID- 7587911
TI  - Proteinuria in NIDDM in south India: analysis of predictive factors.
AB  - There are few data on the risk factors for diabetic nephropathy in the Asian
      Indian population, although several studies have shown a high prevalence of the
      disease in this ethnic group. This study also aimed to assess the role of
      hyperglycaemia and hypertension in the causation and course of nephropathy in
      this population, which has low rates of obesity. Retrospective analysis of two
      groups of non-insulin dependent diabetic (NIDDM) patients, one without
      proteinuria (< 100 mg/day, n = 25) and the other with proteinuria (> or = 500
      mg/day, n = 25), matched for age, sex, duration of diabetes and body mass index
      (BMI) was done to study the factors predisposing to proteinuria and also its
      progression during a 2 year follow-up. Logistic regression analysis showed that
      the factors contributory to proteinuria were initial HbA1 and initial systolic
      blood pressure. The average proteinuria during the follow-up was dependent on the
      initial and average systolic and diastolic blood pressure values. No correlation
      was seen between cholesterol or triglyceride values and the change in
      proteinuria. Creatinine clearance deteriorated in the proteinuric group and this
      was related to the presence of proteinuria and initial diastolic blood pressure.
      This study emphasizes the importance of blood pressure in the progression of
      diabetic nephropathy, even in people who have low BMI. Therefore, good control of
      blood pressure has an important role to play in the management of this condition.

PMID- 7587907
TI  - Experimental and clinical studies on the reduction of erythrocyte sorbitol
      glucose ratios by ascorbic acid in diabetes mellitus.
AB  - In order to confirm the effect of ascorbic acid (AA) on human erythrocyte
      sorbitol accumulation and explore its mechanism of action, the effects of
      ascorbic acid in vitro on the sorbitol (S) and glucose (EG) content of human
      erythrocytes and in particular on the S/EG ratio as a marker of aldose reductase
      (AR) activity were carefully observed. The results showed that both the
      accumulation of erythrocyte sorbitol and the S/EG ratio were strongly reduced by
      the addition of AA. The sorbitol content in the erythrocyte and the S/EG ratio
      were reduced by a maximum of 87.3% and 83.4% and 93.8% and 63.9% when the
      medium's AA concentration was at its peak with 5.6 mmol/l and 28 mmol/l glucose
      in the medium, respectively. The contents of erythrocyte glucose measured
      coincidentally revealed a positive correlation with the ascorbic acid
      concentration in the medium during incubation in 5.6 mmol/l glucose while at a
      higher glucose level (28 mmol/l) in the medium the correlation became negative.
      These results suggested that the polyol pathway could be inhibited effectively by
      AA through its direct action on AR. The results of a double-blind cross-over
      trial using AA tablets or inositol tablets in eight diabetic patients showed that
      the supplementation of 1000 mg AA/day for 2 weeks resulted in reductions of 12.2%
      and 21.8% in erythrocyte sorbitol and red cell sorbitol/plasma glucose (S/PG)
      ratio, respectively (P < 0.05), whereas the fasting plasma glucose levels
      measured coincidentally revealed no changes (P > 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7587913
TI  - Exercise versus overnight albumin excretion rates in subjects with type 1
      diabetes.
AB  - Diabetic nephropathy is the leading cause of new cases of renal failure in the US
      and Europe. An elevated albumin excretion rate (AER) on an overnight urine sample
      is considered an early predictor of end-stage renal failure. An elevated AER on a
      post-exercise urine sample has previously been considered to be an even earlier
      marker of renal damage. In a longitudinal prospective study, 373 subjects with
      insulin-dependent (type 1) diabetes mellitus had a total of 714 renal
      evaluations, each of which included one exercise and two overnight urine
      collections for AER determinations. All subjects were at least 13 years old and
      had diabetes for at least 4 years. There was a strong correlation between
      exercise and overnight AERs (r = 0.74, P < 0.001). For the 60 subjects with an
      initial borderline increase of either overnight or exercise AER, the overnight
      AER values (7.6-20 micrograms/min) progressed first for 52% of subjects whereas
      the exercise AERs (41-114 micrograms/min) progressed first for 43% of subjects
      (5% had simultaneous elevations of both). For the 22 subjects in which an
      abnormal overnight (> 20 micrograms/min) or exercise (> 114 micrograms/min) value
      was detected first, 17 (77%) had an elevated exercise AER first, whereas only 4
      (18%) had an elevated overnight AER first. This study shows that an increase of
      either the exercise or the overnight AER can occur first, dependent upon the
      level of abnormality being considered. The two tests correlate closely with one
      another.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587914
TI  - Central motor conduction time in children and adolescents with insulin-dependent
      diabetes mellitus (IDDM).
AB  - Measurement of central motor conduction time (CMCT) after percutaneous magnetic
      stimulation of the brain is an electrophysiological method that may discover
      subclinical impairment of central nervous system (CNS). In order to detect an
      impairment of CNS, we measured CMCT right (R) and left (L) after percutaneous
      stimulation of the brain in 34 patients affected by insulin-dependent diabetes
      mellitus (IDDM) (16 males and 18 females), aged 16.4 +/- 4.1 years (7.3-23.2
      years), with duration of disease 7.6 +/- 4.9 years (7/12-16 years), and HbA1c
      annual mean 7.41 +/- 1.1% (n.v. 5.14 +/- 0.84%). Twenty-three sex- and age
      matched healthy subjects served as controls. In our IDDM patients we observed a
      delay of CMCT R (P < 0.0005) and L (P < 0.0005) as compared to controls. No
      correlation was found between CMCT (R and L) and chronologic age, duration of
      disease, peroneal motor nerve conduction velocity. No association was observed
      between CMCT (R and L) and HLA antigens. On the basis of IDDM duration, patients
      were divided into 2 groups (G): G I (9 pts) with IDDM < 2 years and G II (25 pts)
      with IDDM > 5 years, 12 of them with precocious signs of one or more
      microangiopathic complications. No difference in CMCT (R and L) was observed
      between the 2 groups and between G I and controls; G II patients had a longer
      delay of CMCT R (P < 0.0001) and L (P < 0.0001) than controls. In G II patients,
      a positive correlation between CMCT R and HbA1c of the 5 years before the test (P
      < 0.025) was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587915
TI  - Change in quality of life along with type 1 diabetes.
AB  - The aim of this study was to recurrently follow quality of life in type 1
      diabetes patients who have switched from syringe to multiple pen injection
      treatment. The insulin pen is a simpler automatically preset device for self
      injection. Seventy-three consecutive outpatients were initially examined in 1988,
      66 of whom were re-examined in 1990. Quality of life was defined as perceived
      well-being and life satisfaction, globally as well as within key domains and
      functions. Various status and retrospective change ratings were repeatedly
      performed by patients and significant others. For a great majority, quality of
      life status was fairly stable between 1988 and 1990. Nine subjects with recent
      incidences of severe socio-medical complications accounted for a great deal (41%)
      of the decline in composite quality of life status recorded. Future-orientation
      and the conduct of the multiple regimen declined in the major fairly stable
      patient group as well. Contrary to the change-in-status outcome referred to, the
      direct retrospective change ratings in 1990 indicated a certain continuing
      consistent improvement over the last 2 years. It was minor, though, in comparison
      with the preceding enhancement attributed to the pen. In spite of the divergent
      mean outcome, the disparate change parameters correlated. The self-rated life
      quality trends were corroborated by ratings by significant others. To a certain
      extent, the mean change bias may reflect coping strategies released by and
      adopted against the strain of the illness. Probably, these primarily coloured the
      more sensitive direct retrospective change ratings. Some bias may also be due to
      a lack of sensitivity of the status ratings. However, the differential change
      assessments may also tease out and illustrate two separate, equally valid,
      patient perspectives, one on their current situation and another one on how it
      has changed. The diabetes illness appears reasonably stable in a majority of the
      subjects over the study interval. There seem to be some remaining satisfactory
      quality of life effects of the pen therapy. The study underscores the benefit of
      undertaking combined retro-/prospective and sufficiently longitudinal analyses
      with simultaneous dual rating operations, to get the most nuanced overview.

PMID- 7587916
TI  - Screening for gestational diabetes in a multi-ethnic population.
AB  - A multi-ethnic population was screened for gestational diabetes mellitus (GDM)
      using a venous plasma glucose estimation, 1 h following a standard 50 g glucose
      load. A significant difference in the ethnic distribution of screen-positivity
      was found. Amongst the screen-positive group the odds ratio (OR) for special care
      baby facility (SCBU) admission and birthweight > 3999 g were both increased (OR =
      1.87 and 1.99). Only limited diagnostic testing by a glucose tolerance test (GTT)
      could be achieved for the screen-positive population. For patients with confirmed
      GDM (two or more abnormal values on a GTT) the OR for SCBU admission was further
      increased to 5.1, while the OR for increased birthweight was only 1.34. Clinical
      attention should be directed towards outcome assessment in order to properly
      evaluate the nature of and place for screening for GDM in multi-ethnic
      populations.

PMID- 7587920
TI  - Abnormal transient rise in hepatic glucose production after oral glucose in non
      insulin-dependent diabetic subjects.
AB  - A transient rise in hepatic glucose production (HGP) after an oral glucosa load
      has been reported in some insulin-resistant states such as in obese fa/fa Zucker
      rats. The aim of this study was to determine whether this rise in HGP also occurs
      in subjects with established non-insulin-dependent diabetes mellitus (NIDDM).
      Glucose kinetics were measured basally and during a double-label oral glucose
      tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control'
      subjects. Twenty minutes after the glucose load, HGP had increased 73% above
      basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P <
      0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at
      a similar time. In contrast, the control subjects showed no rise in HGP or plasma
      glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and
      control subjects. A 27% increase in the rate of gut-derived glucose absorption
      was also observed in the NIDDM group, which could be the result of increased gut
      glucose absorption or decreased first pass extraction of glucose by the liver.
      Therefore, in agreement with data in animal models of NIDDM, a transient rise in
      HGP partly contributes to the hyperglycemia observed after an oral glucose load
      in NIDDM subjects.

PMID- 7587919
TI  - Effects of early introduction of intensive insulin therapy on the clinical course
      in non-obese NIDDM patients.
AB  - In order to reconsider the extent of indication of insulin therapy in non-insulin
      dependent diabetes mellitus (NIDDM), we performed the following trial in a
      prospective fashion. At the beginning phase of treatment for diabetes, we
      introduced intensive insulin therapy in 22 non-obese (Body mass index
      approximately 24 kg/m2) NIDDM patients without proliferative retinopathy, who
      were selected in a standardized fashion, avoiding any arbitrary choice. None had
      received oral hypoglycemic agents (OHA) or insulin yet. By administering insulin
      3 or 4 times a day, strict glycemic control was attained and maintained, and then
      the insulin dose was gradually lowered while keeping good glycemic control. In
      patients whose glycemic control was maintained at an excellent level for more
      than 7 days under an insulin dosage lower than 8 u/day, insulin therapy was
      discontinued. As a result, 15 patients (68%) attained good glycemic control both
      without insulin and OHA almost within a month and 6 patients (27%) shifted to
      OHA. It is recommended to introduce intensive insulin therapy in non-obese NIDDM
      patients without proliferative retinopathy and to aim at attaining good glycemic
      control both without insulin and OHA.

PMID- 7587918
TI  - Intensive insulin therapy prevents the progression of diabetic microvascular
      complications in Japanese patients with non-insulin-dependent diabetes mellitus:
      a randomized prospective 6-year study.
AB  - To examine whether intensive glycemic control could decrease the frequency or
      severity of diabetic microvascular complications, we performed a prospective
      study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM)
      treated with multiple insulin injection treatment. A total of 110 patients with
      NIDDM was randomly assigned to multiple insulin injection treatment group (MIT
      group) or to conventional insulin injection treatment group (CIT group). Fifty
      five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30
      mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the
      other 55 NIDDM patients who showed simple retinopathy and urinary albumin
      excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The
      appearance and the progression of retinopathy, nephropathy and neuropathy were
      evaluated every 6 months over a 6-year period. The worsening of complications in
      this study was defined as an increase of 2 or more steps in the 19 stages of the
      modified ETDRS interim scale for retinopathy and an increase of one or more steps
      in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy.
      The cumulative percentages of the development and the progression in retinopathy
      after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the
      primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT
      group in the secondary-intervention cohort (P = 0.049). The cumulative
      percentages of the development and the progression in nephropathy after 6 years
      were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention
      cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups
      in the secondary-intervention cohort (P = 0.044). In neurological tests after 6
      years, MIT group showed significant improvement in the nerve conduction
      velocities, while the CIT group showed significant deterioration in the median
      nerve conduction velocities and vibration threshold. Although both postural
      hypotension and the coefficient of variation of R-R interval tended to improve in
      the MIT group, they deteriorated in the CIT group. In conclusion, intensive
      glycemic control by multiple insulin injection therapy can delay the onset and
      the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese
      patients with NIDDM. From this study, the glycemic threshold to prevent the onset
      and the progression of diabetic microangiopathy is indicated as follows; HbA1c <
      6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180
      mg/dl.

PMID- 7587921
TI  - Decreased cell-mediated immunity in patients with non-insulin-dependent diabetes
      mellitus.
AB  - Peripheral blood mononuclear cells from patients with non-insulin-dependent
      diabetes mellitus (NIDDM) show reduced proliferative response to
      phytohemagglutinin (PHA) and other mitogens. This study was undertaken to
      determine whether this reduced lymphocyte proliferation is mediated by a
      decreased production of cytokine or decreased expression of interleukin-2
      receptor (IL-2R). Mononuclear cells from NIDDM patients (n = 34) and healthy
      controls (n = 22) were cultured in RPMI-1640 media containing PHA, concanavalin-A
      and phorbol myristate acetate. NIDDM patients showed reduced [3H]thymidine uptake
      (57% of controls, P < 0.01), reduced percentage of IL-2R-positive cells (61% of
      controls, P < 0.02) and increased level of tumor necrosis factor (TNF)-alpha
      (200% of controls, P < 0.05). The percentage of complement receptor (CR) 3
      positive monocytes from NIDDM patients was also decreased (72% of controls, P <
      0.05). However, the production of IL-1 beta, IL-2 and interferon-gamma, the
      percentages of pan T cells (CD3), T helper cells (CD4), T suppressor cells (CD8),
      the ratio of CD4/CD8 and the expression of CR1 and Fc receptors for
      immunoglobulin G (Fc gamma RII and Fc gamma RIII) were not significantly
      different between NIDDM patients and healthy subjects. Human recombinant IL-2 was
      unable to restore the [3H]thymidine uptake by PHA-stimulated mononuclear cells
      from NIDDM patients. Elevation of glucose concentration up to 27.8 mmol/l in the
      culture medium did not suppress the [3H]thymidine uptake and IL-2R expression by
      activated lymphocytes from healthy subjects. The decreased expression of IL-2R on
      activated lymphocytes might be responsible for the insufficient lymphocyte
      proliferation in NIDDM patients. These findings suggest that decreased expression
      of CR3 on monocytes, decreased lymphocyte proliferation and decreased IL-2R
      expression despite a higher production of TNF-alpha may explain the impaired cell
      mediated immunity seen in NIDDM patients.

PMID- 7587922
TI  - Atonic bladder in diabetes mellitus due to 3243 bp mitochondrial tRNA(Leu)(UUR)
      mutation.

PMID- 7587917
TI  - Role of advanced glycation end-products (AGE) in late diabetic complications.
AB  - To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and
      its possible correlation with late diabetic complications, AGE levels were
      measured by spectrofluorimetry in eye lens and sciatic nerve proteins and
      isolated tail tendon collagen of rats with experimental diabetes of 3- and 6
      month duration. The values obtained were compared to those from age-matched
      control rats and correlated with cataract presence and somatosensory evoked
      potential (SEP) alterations. Diabetic animals had increased AGE levels in all
      tissues at both times; cataract developed in 29% of diabetic rats at 3 months and
      in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both
      at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/
      1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level
      differences were observed when cataract presence was considered. Interestingly,
      in diabetic rats, increased sciatic nerve AGE levels were associated with reduced
      SEP. These data show that: (1) AGE levels are increased as early as 3 months from
      development of hyperglycemia; (2) other factors, in addition to an enhanced rate
      of fluorescent AGE formation, might play important roles in the pathogenesis of
      diabetic cataract; (3) increased peripheral nerve AGE levels are associated with
      SEP alterations.

PMID- 7587923
TI  - An alpha-glucosidase inhibitor, AO-128, retards carbohydrate absorption in rats
      and humans.
AB  - The present study was designed to determine the possible significance of a
      therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the
      breath hydrogen concentration, which is an index of the amount of unabsorbed
      carbohydrate in the large intestine. Post-prandial hyperglycemia is common among
      diabetic patients. AO-128, a potent alpha-glucosidase inhibitor, suppressed post
      prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of
      0.2 mg with each meal. These volunteers increased the breath hydrogen
      concentration in response to ingestion of non-absorbable lactulose, but decreased
      only slightly its concentration from the basal level after sucrose ingestion,
      indicating complete absorption. When AO-128 (0.2 mg) was given with sucrose,
      hydrogen production increased only slightly compared with placebo, suggesting
      that the inhibitory effect of AO-128 on sucrose absorption was minimal. Only 5 g
      of the 100 g of sucrose was not absorbed and this 5% reduction is too small to
      explain the observed inhibitory effect on the post-prandial rise in plasma
      glucose. Sucrose loading in rats (about 443 mg) sharply increased blood glucose
      and was accompanied by the rapid disappearance of sucrose from the upper small
      intestine. AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose
      after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small intestinal
      absorption, but did not induce an influx of sucrose into the cecum and large
      intestine, while the higher dose (0.1 mg/kg) caused an increased influx of
      sucrose into the large bowel. These results indicated that AO-128 retards the
      absorption of carbohydrate and reduces post-prandial hyperglycemia.

PMID- 7587924
TI  - Rapid gastric emptying and pathological changes of vagus nerve in the
      spontaneously diabetic Chinese hamster.
AB  - To estimate autonomic neuropathy in the spontaneously diabetic Chinese hamster,
      which is an established strain for the non-obese non-insulin-dependent diabetes
      mellitus model, gastric emptying and morphometric analysis of the vagus nerve
      were studied in 12-month-old spontaneously diabetic Chinese hamsters (duration of
      diabetes was 9 months). Gastric emptying was determined by the phenol red method.
      Vagus was obtained from just above the diaphragm. Morphometric analysis of
      myelinated fibers was performed light-microscopically using semi-thin sections
      and unmyelinated fibers were studied electron-microscopically using ultra-thin
      sections. Gastric emptying of spontaneously diabetic Chinese hamster was
      significantly increased compared with control (86.6 +/- 1.9 vs. 51.2 +/- 3.4, P <
      0.01). Myelinated fibers of the spontaneously diabetic Chinese hamster were not
      different from control animals, while the size of unmyelinated fibers in the
      spontaneously diabetic Chinese hamster was significantly decreased. These data
      suggest that pathological changes in unmyelinated fibers, which consist mainly of
      afferent fibers, might play a role in gastric motor dysfunction in the
      spontaneously diabetic Chinese hamster.

PMID- 7587925
TI  - Nocturnal oxygen desaturation in diabetic patients with severe autonomic
      neuropathy.
AB  - The aim of the study was to assess whether diabetic patients with autonomic
      neuropathy suffer from arterial oxygen desaturation during sleep. Two groups of
      subjects were evaluated: group I consisted of 12 patients with cardiovascular
      autonomic neuropathy (five with insulin-dependent diabetes mellitus (IDDM) and
      seven with non-insulin-dependent diabetes mellitus (NIDDM)). Group II consisted
      of 8 healthy subjects. Age, percentage male and body mass index (BMI) were
      similar in both groups. Exclusion criteria were abnormalities in arterial gas
      measurements, chest X-ray, spirometry or the presence of cardiac arrhythmias,
      obesity, uremia, alcohol abuse and use of drugs other than insulin and oral
      hypoglicemic agents. The results of arterial oximetry when the subjects were
      awake showed no differences between the two groups. However, during sleep,
      diabetics with autonomic neuropathy had an increased number of desaturation
      episodes under 85% and those episodes were more prolonged. The results suggest
      that diabetics with autonomic neuropathy might have abnormal control of
      respiration that is apparent only during sleep.

PMID- 7587926
TI  - Induction of nasal carboxylesterase in F344 rats following inhalation exposure to
      pyridine.
AB  - Carboxylesterases (CEs) in the nasal mucosa metabolize some inhaled esters,
      including industrially important acrylates and acetates, to toxic acid
      metabolites that produce site-specific lesions in the nasal epithelium. The
      metabolic capacity of CEs in the normal nasal mucosa is theoretically sufficient
      to protect the lower respiratory tract from toxicant-induced injury at
      concentrations of acrylates and acetates likely to be inhaled in industrial
      environments. Thus, alterations in the metabolism and toxicity of these
      substrates would be predicted with changes in the amount or activity of CE in the
      nasal mucosa. Although many other nasal enzymes have been reported to be
      relatively refractory to induction, the amount of CE in the nasal mucosa can be
      increased by inhalant exposure. In the liver, expression of CEs may be elevated
      in response to exposure to P450 inducers. To examine this phenomenon in the nose
      with the widely used industrial solvent pyridine, we examined the effect of
      pyridine inhalation at the threshold limit value concentration of 5 ppm, or at
      444 ppm, 6 hr/day for 4 days on the localization and amount of immunoreactive CE
      in olfactory mucosas of F344/N rats. CE immunoreactivity was increased in
      Bowman's glands following exposure to 5 or 444 ppm pyridine, and in sustentacular
      cells most notably following the 5 ppm exposure. Quantitative densitometry showed
      a statistically significant, dose-related increase in the density of
      immunoreactive CE in Bowman's glands of pyridine-exposed rats. These results
      indicate pyridine, and possibly other solvents, can induce nasal CE, an enzyme
      not directly involved in the metabolism of those solvents, following low-dose,
      short-term exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587928
TI  - The antibiotic tiamulin is a potent inducer and inhibitor of cytochrome P4503A
      via the formation of a stable metabolic intermediate complex. Studies in primary
      hepatocyte cultures and liver microsomes of the pig.
AB  - Tiamulin is a semisynthetic antibiotic frequently used in agricultural animals.
      The drug has been shown to produce clinically important--often lethal-
      interactions with other compounds that are simultaneously administered. To
      explain this, it has been suggested that tiamulin selectively inhibits oxidative
      drug metabolism via the formation of a cytochrome P450 metabolic intermediate
      complex. The aim of the present study was to provide further support for this
      hypothesis. When hepatic microsomes and cultured primary pig hepatocytes were
      incubated with tiamulin, a maximum in the absorbance spectrum at 455 nm was
      observed, which disappeared after adding KFe(CN)6. When hepatocytes were
      incubated with tiamulin for 72 hr, cytochrome P450 content and cytochrome P4503A
      apoprotein levels were increased. Tiamulin strongly inhibited and concentration
      dependently inhibited the hydroxylation rate of testosterone at the 6 beta
      position in both microsomes and hepatocytes, and the microsomal N-demethylation
      rate of ethylmorphine. Other testosterone hydroxylations were inhibited to a
      lesser extent or not affected. The relative inhibition of the hydroxylation of
      testosterone at the 6 beta-position was more pronounced in microsomes from
      rifampicin- and triacetyloleandomycin-treated pigs. The results indicate that
      cytochrome P450 complex formation can at least partly explain the interactions
      observed with tiamulin. Tiamulin seems to be a strong, probably selective,
      inhibitor of the cytochrome P4503A subfamily and an interesting tool for further
      research.

PMID- 7587927
TI  - The duration of induction and species influences the downregulation of cytochrome
      P450 by the interferon inducer polyinosinic acid-polycytidylic acid.
AB  - Interferon (IFN) has long been recognized to downregulate cytochrome P450
      mediated drug metabolism. Some investigations have shown that induced P450
      enzymes tend to be more resistant to the depressant effect of IFN, whereas
      constitutive forms of P450 are uniformly depressed by IFN. We examined the effect
      of varying the period of induction of P450 proteins (CYP1A1, CYP2B, and CYP2E1)
      in two animal species. In mice, the IFN inducer polyinosinic acid-polycytidylic
      acid depressed the constitutive and induced enzyme activities of ethoxyresorufin
      O-deethylase, benzyl-oxyresorufin O-dealkylase, and p-nitrophenol hydroxylase at
      all levels of induction. The depression of P450 proteins (CYP1A1, CYP2B10, and
      CYP2E1) was confirmed by immunoblotting. In contrast, the downregulation of the
      same enzyme activities observed at 0 and 24 hr of induction did not occur after
      48 or 72 hr of induction in the rat. Immunoblotting confirmed that CYP1A1,
      CYP2B1, and CYP2E1 levels were downregulated in control and at low levels of
      induction, but were not affected at high levels of induction. The response of
      constitutive enzyme activities to downregulation by IFN was not influenced by any
      of the induction protocols in rats or mice. Thus, cytochrome P450 induction does
      not invariably confer resistance to IFN-mediated downregulation of the enzymes,
      and the mechanism of induction does not determine the response to IFN. It seems
      that the species and duration or level of induction are the major influences on
      the observed response of P450 enzymes to IFN-evoked downregulation.

PMID- 7587929
TI  - Identification of phenobarbital N-glucuronides as urinary metabolites of
      phenobarbital in mice.
AB  - Mice were evaluated for their ability to form phenobarbital N-glucuronides.
      Following oral administration of [14C]phenobarbital to mice, a radiolabeled
      phenobarbital metabolite cochromatographed with synthetic standards of
      phenobarbital N-glucuronides. The phenobarbital N-glucuronides were partially
      purified from the mouse urine as phenobarbital N-methylglucuronates. The
      phenobarbital N-methylglucuronates isolated from mouse urine had similar
      chromatographic and spectroscopic properties as synthetic standards. The
      diastereomers of phenobarbital N-glucuronides and phenobarbital N-glucosides
      accounted for 7.8 +/- 2.3% and 1.6 +/- 0.6%, respectively, of the radioactivity
      excreted in mouse urine in the first 48 hr after dosing. This study indicates
      that the mouse may be a suitable species to study both N-glucosidation and N
      glucuronidation simultaneously as metabolic pathways for barbiturates.

PMID- 7587930
TI  - Effect of model inducers on cytochrome P450 activities of human hepatocytes in
      primary culture.
AB  - The dealkylations of 7-ethoxy- and 7-pentoxyresorufin,p-nitrophenol
      hydroxylation, and regio- and stereoselective hydroxylation of testosterone were
      measured to study the stability and inducibility of cytochrome P450 activities in
      cultured human hepatocytes. The results showed that human hepatocytes in primary
      culture retain the ability to increase specific cytochrome P450 activities upon
      incubation with inducers. 3-Methylcholanthrene produced a strong increase (6- to
      21-fold over control) in 7-ethoxyresorufin O-deethylase activity and a small
      enhancement (1.5- to 2.5-fold) of the p-nitrophenol hydroxylation rate.
      Incubation of cells with phenobarbital resulted in moderate increases in 7
      pentoxyresorufin O-depentylation (1.5- to 2-fold) and in testosterone
      hydroxylation at 16 alpha (1.5- to 4.5-fold) and 16 beta (1.3- to 4-fold)
      positions. Ethanol specifically increased p-nitrophenol hydroxylase activity (1.5
      to 3.5-fold) and reduced 15 beta- and 6 beta-hydroxylations of testosterone.
      Treatment of hepatocytes with dexamethasone produced an increase of almost all
      the activities studied, with 6 beta- (2- to 3-fold) and 16 beta
      hydroxytestosterone (1.4- to 2.4-fold) formation showing the greatest
      enhancement. Clofibric acid exposure resulted in 1.5- to 3-fold increases in 7
      pentoxyresorufin O-depentylase and in testosterone 6 beta- and 2 beta-hydroxylase
      activities. Isosafrol selectively increased 7-ethoxyresorufin O-deethylase
      activity (2- to 3-fold), and it moderately reduced the other activities studied.

PMID- 7587931
TI  - Acetylation and its role in the mutagenicity of the antihypertensive agent
      hydralazine.
AB  - 1-Hydrazinophthalazine [hydralazine (HDZ)] is a hydrazine derivative that is a
      direct acting vasodilator effective in the treatment of essential hypertension.
      HDZ is biotransformed by the phase II conjugation enzyme N-acetyltransferase
      (NAT) forming acetyl HDZ, which spontaneously cyclized to the stable product 3
      methyl-s-triazolo- [3,4-alpha]-phthalazine (MTP). Therapeutic use of HDZ has
      resulted in adverse side effects, specifically a drug-induced systemic lupus
      erythematosus. Slow acetylators are more likely than rapid acetylators to develop
      this toxicity. Bacteria expressing different levels of NAT were used to test the
      hypothesis that acetylation of HDZ decreases its mutagenic potential. The
      variation in NAT activities was confirmed by incubating bacterial cultures with
      HDZ, and the formation of MTP was monitored by HPLC. At 1.0 mg/ml HDZ, YG1029
      (NAT overexpresser) produced 5.3 times the amount of MTP as TA100 (normal NAT
      expresser), and this production was linear for 20 hr. In the Salmonella
      mutagenesis assay, HDZ produced a dose- and strain-dependent increase in the
      number of revertants observed. Exposure to 4 mg HDZ/plate resulted in 1000
      revertants in the overexpressing strain, YG1029, whereas both TA100 and
      TA100/1,8DNP6, which express normal levels and lack the NAT protein respectively,
      produced 1600 revertants. Colony hybridization analysis using probes for each of
      the six possible TA100 reverting mutations was performed to determine the nature
      of the mutations. The G:C to T:A transversion was the only mutation whose
      frequency was increased significantly by HDZ. Fifty-four percent of the induced
      vs. 25% of the spontaneous mutations were C to A transversions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7587932
TI  - Disposition and reactivity of ibuprofen and ibufenac acyl glucuronides in vivo in
      the rhesus monkey and in vitro with human serum albumin.
AB  - The disposition of ibuprofen and ibufenac, an analog of ibuprofen with a history
      of severe adverse reactions, was investigated in Rhesus monkeys after oral
      administration. Plasma concentrations of the parent drugs and their glucuronides
      were measured by a direct HPLC method. Ibuprofen and ibufenac were rapidly
      absorbed and metabolized to their acyl glucuronides. The pharmacokinetic
      parameters of ibuprofen and ibufenac exhibited notable interanimal variability.
      Ibufenac tended to have a higher area under the plasma concentration vs. time
      curve (AUC), and its apparent clearance was lower. The plasma levels of acyl
      glucuronides were lower than parent drugs; the ratio of AUC in plasma for
      glucuronide/parent drug was 22.8% and 10.5% for ibuprofen and ibufenac,
      respectively. The degradation of ibufenac glucuronide in vitro was faster than
      ibuprofen glucuronide in aqueous buffer, human serum albumin, and human plasma
      solutions. Covalent binding of parent drug to protein via the acyl glucuronides
      was observed both in vitro and in vivo. The maximum protein adduct formed in vivo
      with ibufenac was 60% higher than found for ibuprofen, although exposure in
      plasma to its reactive acyl glucuronide, as measured by AUC, was lower. These
      data indicate that ibufenac glucuronide is a more reactive metabolite than
      ibuprofen glucuronide in vitro and in vivo.

PMID- 7587933
TI  - An improved pharmacodynamic model for formation of methemoglobin by antimalarial
      drugs.
AB  - The widely used 8-aminoquinoline antimalarial group of compounds and the
      derivatives such as WR242511 that are being developed for possible prophylactic
      anticyanide applications have complex interactions with erythrocytes.
      Methemoglobin (MetHb) levels following the use of this drug predicted by earlier
      authors grossly deviated from the observed steady state levels under multiple
      dose conditions. We propose a pharmacokinetic-pharmacodynamic model to
      characterize literature data for blood levels of MetHb generated after
      administration of WR242511. The model is based on an indirect mechanism involving
      WR242511 putative metabolite concentration, Cm on the formation of MetHb (rate
      constant, kr) and on depletion of reducing equivalents leading to accumulation of
      MetHb. Eventual depletion of MetHb is modeled as related to the disposition of
      both the drug metabolite and MetHb. The rate of change of MetHb concentration in
      the blood under the influence of a dose of WR242511 in dogs was governed by this
      relationship: d[MetHb]/d(t) = kr.Cm.[Hb]-kh.[MetHb], where kr is 2.9 x 10(-5)
      ml.ng-1.hr-1 and kh is 0.0418 hr-1. This model was validated with multiple-dose
      data. The model is simple and compatible with the physiological behavior of MetHb
      in vivo under single-dose and multiple-dose conditions of WR242511
      administration.

PMID- 7587935
TI  - Presystemic elimination of morphine in anesthetized rabbits. Contribution of the
      intestine, liver, and lungs.
AB  - To assess the role of the intestine and the lung in the first-pass uptake of
      morphine relative to that of the liver, five groups of 6-7 New Zealand rabbits
      were used. A control group of conscious rabbits received 2 mg/kg of morphine iv.
      The remaining groups included anesthetized rabbits who received morphine into the
      aortic cross (2 mg/kg), the jugular vein (2 mg/kg), the portal vein (14 mg/kg),
      or into the duodenum (20 mg/kg). Multiple blood samples were withdrawn for 3 hr
      from the abdominal aorta, and morphine and morphine-6-glucuronide were assayed by
      HPLC. Anesthesia and surgery decreased morphine presystemic clearance from 264 +/
      14 to 194 +/- 12 ml/min/kg (p < 0.05). When morphine was injected into the
      aortic cross, the area under morphine plasma concentration-time curve (AUCM 0-
      >infinity) normalized by the dose was 7.81 +/- 0.56 10(-3) kg min/ml, a value
      that decreased to 5.26 +/- 0.36 (p < 0.05), 2.50 +/- 0.35 (p < 0.05), and 0.87 +/
      0.10 (p < 0.05) 10(-3) kg min/ml when morphine was injected before the lung,
      liver, or intestine, respectively. The extraction ratio of morphine by the lung,
      liver, and intestine was 0.33, 0.52, and 0.65, respectively. Compared with the
      aortic route, the AUCM6G 0-->infinity normalized by the dose ratio tended to be
      greater (p > 0.05) when morphine was injected into the jugular and portal veins,
      suggesting that morphine-6-glucuronide is not the major product result of
      morphine first-pass uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587936
TI  - Covalent binding of carbamazepine oxidative metabolites to neutrophils.
AB  - Carbamazepine therapy is associated with several types of idiosyncratic drug
      reactions, including hematological disorders. In previous studies, we found that
      carbamazepine was metabolized by the myeloperoxidase/H2O2 system of activated
      neutrophils, and covalent binding of the drug to neutrophils was observed.
      Several metabolites were identified, including 9-acridine carboxaldehyde.
      Iminostilbene, a minor hepatic metabolite of carbamazepine, was metabolized to a
      much greater extent than carbamazepine to similar metabolites, including 9
      acridine carboxaldehyde. In the present study, the covalent binding of
      iminostilbene to activated neutrophils was also found to be 10-fold greater than
      that of carbamazepine. In addition, the binding of 9-acridine carboxaldehyde to
      neutrophils was 100-fold that of carbamazepine and did not require activation of
      the neutrophils. This suggests that this aldehyde is the reactive intermediate
      responsible for much of the binding. To understand possible mechanisms of
      covalent binding, we investigated the reaction of 9-acridine carboxaldehyde with
      nucleophiles and found that a reaction occurs with primary amines, such as n
      butylamine and N-alpha-acetyllysine, with the formation of an imine. Sodium
      cyanoborohydride was used to reduce the imine to a stable secondary amine. This
      suggests a possible mechanism for 9-acridine carboxaldehyde binding to
      neutrophils that could involve physiological reducing systems in place of the
      borohydride. 9-Acridine carboxaldehyde may be responsible for some of the adverse
      reactions associated with carbamazepine, especially those that involve bone
      marrow.

PMID- 7587937
TI  - Oxidation at C-1 controls the cytotoxicity of 1,1-dichloro-2,2- bis(p
      chlorophenyl)ethane by rabbit and human lung cells.
AB  - Isolated rabbit Clara cells and a transformed human bronchial epithelial cell
      line, BEAS-2B, were used to investigate the mechanism of cytotoxicity of 1,1
      dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), a persistent insecticide and stable
      metabolite of 1,1,1-trichloro-2,2- bis(p-chlorophenyl)ethane. Both BEAS-2B cells
      and rabbit Clara cells were highly susceptible to DDD toxicity and were partially
      protected by 1-aminobenzotriazole, a suicide substrate inhibitor of cytochrome
      P450 enzymes. DDD (0.05 mM) killed 47 +/- 1.8% of rabbit Clara cells and 42 +/-
      7.9% of BEAS-2B cells after 3 hr and 84 +/- 3.0% of rabbit Clara cells and 80 +/-
      14% of BEAS-2B cells after 6 hr. Consequently, DDD is the most potent Clara cell
      toxicant recognized to date. The cytotoxicity of DDD to these cells was decreased
      by deuterium substitution at the C-1 position. Rabbit Clara cells and pulmonary
      microsomes incubated with 14C-DDD produced the fully oxidized acetic acid
      metabolite 2,2'-bis(p- chlorophenyl)acetic acid (DDA), but DDA was not formed by
      Clara cells when DDD was coincubated with 1-aminobenzotriazole. These results
      support the hypothesis that the cytotoxicity of DDD to susceptible subpopulations
      of rabbit and human lung cells is, at least in part, caused by cytochrome P450
      mediated oxidation of DDD at C-1. A required step for the production of the
      cytotoxic intermediate is proposed to be the formation of a highly reactive acyl
      halide intermediate that is readily hydrolyzed to a stable, nontoxic metabolite,
      DDA.

PMID- 7587938
TI  - Identification of two regioisomeric monocarboxylic acid metabolites of
      losoxantrone (DuP 941; Biantrazole) excreted in human urine.

PMID- 7587934
TI  - Selectivity and kinetics of inactivation of rabbit hepatic cytochromes P450 2B4
      and 2B5 by N-aralkylated derivatives of 1-aminobenzotriazole.
AB  - The kinetics of mechanism-based inactivation of phenobarbital-inducible rabbit
      hepatic cytochromes P450 2B4 and 2B5 by N-benzyl-(BBT) and N-alpha-methylbenzyl
      (alpha MB) 1-aminobenzotriazole were investigated using reconstituted P450 2B4, a
      stable heterologous expression system, and hepatic microsomes. Low micromolar
      concentrations of the 1-aminobenzotriazole derivatives caused reversible
      inhibition as well as rapid inactivation of reconstituted P450 2B4 and
      recombinant P450 2B4 and 2B5. In contrast, even at a 1000-fold higher
      concentration, aminobenzotriazole inactivated the expressed P450 2B enzymes less
      rapidly. Preincubation of phenobarbital-induced hepatic microsomes with BBT and
      alpha MB resulted in concentration-dependent decreases in marker activities of
      P450 2B4 and 2B5, benzyloxyresorufin O-debenzylase and androstenedione 15 alpha
      hydroxylase, respectively. BBT caused the inactivation of P450 2B4 and 2B5 in
      hepatic microsomes with apparent Kl values of 1.9 and 2.4 microM and maximal rate
      constants of 0.29 and 0.18 min-1, respectively. alpha MB inactivated both P450 2B
      enzymes with similar Kl values (approximately 7 microM) and maximal rate
      constants only slightly higher for 2B4 compared with 2B5 (0.68 vs. 0.55 min-1).
      Similar P450 2B selectivity of BBT and alpha MB in both hepatic microsomes and
      the stable expression system further validates this new expression system and the
      use of the selective markers identified for 2B4 and 2B5 in hepatic microsomes.
      The results also provide a mechanistic basis for the high potency of the N
      aralkylated 1-aminobenzotriazole derivatives in vivo and suggest that treatments
      that inactivate 2B4 will also lead to 2B5 inactivation.

PMID- 7587939
TI  - Pharmacokinetics and presystemic hepatic first-pass elimination of a novel sigma
      receptor antagonist, DuP 734, in the rat.

PMID- 7587940
TI  - Urine chromium screening.

PMID- 7587941
TI  - Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine
      enantiomers.
AB  - The 4-hydroxylation of S(+)- and R(-)-methamphetamine by rat liver microsomes was
      examined in Sprague-Dawley and Dark Agouti strains to determine the role of
      cytochrome P4502D (CYP2D) subfamily isozymes in catalyzing the reaction. In the
      study, anti-P450-BTL IgG, bufuralol, and quinine, a substrate and inhibitors of
      CYP2D isozymes, respectively, were found to block approximately 90% of the
      reaction as catalyzed by microsomes from Sprague-Dawley rats. Reconstituted
      systems of CYP2D isozymes purified from rat liver microsomes also mediated the
      reaction. These observations and the minimal activity found in microsomes from
      Dark Agouti rats support the notion that methamphetamine, like other
      phenylisopropylamine compounds, is oxidized on the 4-position of the aromatic
      ring by CYP2D isozymes.

PMID- 7587942
TI  - Metabolism of cyclosporin G in the mouse, rat, and dog.
AB  - Cyclosporin G (CsG; Sandoz compound OG 37-325) is a cyclic undecapeptide with
      potent, immunosuppressive activity and is currently in clinical testing for
      prevention of transplanted solid organ rejection. Although structurally similar
      to cyclosporin A (CsA), results in animals suggest that CsG has a reduced
      potential for nephrotoxicity when compared with CsA, while retaining equivalent
      therapeutic efficacy. In the present study, the major metabolic pathways of CsG
      in the mouse, rat, and dog were investigated using radiolabeled drug substance to
      determine if interspecies differences in metabolism exist. The results indicated
      that the major metabolic pathways in these animal species are similar to those
      previously reported for CsA, including oxidative modifications at amino acids 1,
      4, and 9, and concomitant cyclization of amino acid 1 in two of these
      metabolites. Moreover, the seven major CsG metabolites (designated GM19, GM1c9,
      GM4N9, GM1, GM9, GM1c, and GM4N) observed in animal excreta and/or blood were
      identical to those identified in humans. The major circulating metabolite in
      blood was GM9 (9-hydroxylated CsG) in all species. In addition, numerous
      unidentified minor metabolites were observed. Renal excretion was a minor
      elimination pathway, with the majority of drug-related material excreted via the
      fecal route. In conclusion, CsG was found to proceed through the same metabolic
      pathways in three animal species and humans, and that species differences in
      metabolism were primarily because of differences in the relative importance of
      the pathways observed.

PMID- 7587943
TI  - Glutathione depletion kinetics with acetaminophen. A simulation study.
AB  - A tubular-flow model with known published parameters on glutathione (GSH)
      synthesis, degradation, and transport was developed to examine the distributed-in
      space bimolecular reaction of GSH conjugation with acceptor substrates.
      Simulations were performed to obtain the vascular and intracellular GSH
      concentrations in the absence and presence of acetaminophen. Zonal localization
      of GSH was found to be effectively modified upon varying the activities for GSH
      synthesis and degradation along the sinusoidal flow path. A periportal (zone 1)
      GSH distribution resulted when GSH synthetic activity was distributed anterior to
      the degradation activity (models A and D); a perivenous (zone 3) GSH enrichment
      existed when these activities were reversed (model B), whereas when the synthetic
      and degradation activities for GSH were homogeneously distributed (model C), GSH
      concentration was unchanged in all zones. Although the zonation of GSH was model
      dependent (models A-D ), only minor differences were found to exist for the
      length-averaged tissue GSH concentration (5.8-6 mumol/g liver) and the outflow of
      the liver (approximately 15 microM). With acetaminophen, a substrate known to
      deplete GSH via its reactive intermediate, N-acetyl-p-quinoneimine (NAPQI),
      acinar GSH patterns were not greatly perturbed at concentrations < 1 mM. At 10 mM
      acetaminophen, however, differential patterns of GSH zonal depletion were
      observed among models, although there was virtually no difference in the length
      averaged intracellular GSH concentration (3 mumol/g liver) nor in the formation
      of the acetaminophen GSH adduct, with the latter being rate-limited by the
      bioactivation of acetaminophen to NAPQI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587944
TI  - Metabolism of terfenadine associated with CYP3A(4) activity in human hepatic
      microsomes.
AB  - Terfenadine (Seldane) undergoes extensive metabolism to form azacyclonol and
      terfenadine alcohol. Terfenadine alcohol is subsequently metabolized to
      azacyclonol and terfenadine acid. Although testosterone 6 beta-hydroxylation
      [CYP3A(4)] has been shown to be the principal enzyme involved in the first step
      in terfenadine's biotransformation (formation of azacyclonol and terfenadine
      alcohol), the enzymes catalyzing the subsequent metabolic steps in the conversion
      of terfenadine alcohol to azacyclonol and terfenadine acid have not been
      identified. The purpose of these studies was to determine the role of cytochrome
      P450 isoforms in the biotransformation of terfenadine and terfenadine alcohol. To
      this end, both terfenadine and its alcohol were incubated with 10 individual
      human liver microsomal samples that have been characterized for major isozyme
      activities. The metabolites and parent drugs were quantified by HPLC. The
      formation of azacyclonol and terfenadine alcohol from terfenadine is confirmed to
      be catalyzed predominantly by CYP3A(4) isozyme, and the ratio of the rate of
      terfenadine alcohol formation to that of azacyclonol is 3:1. Involvement of the
      CYP3A(4) in terfenadine metabolism was further confirmed by the following
      studies: a) inhibition of terfenadine alcohol formation by ketoconazole and
      troleandomycin, two specific inhibitors of CYP3A(4), and b) time course of
      terfenadine alcohol formation by cloned human CYP3A(4). When terfenadine alcohol
      was used as substrate, both the terfenadine acid and azacyclonol formation were
      also catalyzed by CYP3A(4) isozyme. However, the rate of formation of the
      terfenadine acid metabolite is almost 9 times faster than that of azacyclonol.
      The net ratio of terfenadine acid to azacyclonol is 2:1.

PMID- 7587945
TI  - Input rate-dependent stereoselective pharmacokinetics. Experimental evidence in
      verapamil-infused isolated rat livers.
AB  - The input rate dependency of verapamil (VER) kinetics was studied in single-pass
      isolated rat livers perfused with a Krebs-bicarbonate buffer solution, containing
      albumin and red blood cells, at a flow rate of 15 ml/min. Racemic VER was infused
      at a constant rate of approximately 50 (low dose, N = 5) or approximately 100
      (high dose, N = 5) micrograms/min through the inlet catheter (portal vein). Inlet
      and outlet samples were taken periodically over 90 min. Additionally, liver
      samples were obtained at the end of infusion. Perfusate and liver samples were
      analyzed using a chiral liquid chromatographic method for determination of the
      individual enantiomers of VER and its metabolites, norverapamil (NOR). After the
      low-dose infusion, the hepatic availability of S-VER (0.102 +/- 0.021) was
      greater than that of its antipode (0.071 +/- 0.020). A 2-fold increase in the
      input rate resulted in a significant increase in the hepatic availabilities of S
      VER (0.195 +/- 0.040) and R-VER (0.182 +/- 0.048). However, the increase was more
      pronounced for R-VER, resulting in a significant decrease in the S:R availability
      ratio from 1.47 +/- 0.20 (low dose) to 1.09 +/- 0.14 (high dose) and loss of
      stereoselectivity at the high dose. The S:R ratio of NOR concentration was also
      input rate-dependent. However, the degree of stereoselectivity for the outlet
      concentrations of NOR (S:R ratios 2.42 +/- 0.42 and 1.88 +/- 0.20 for the low and
      high doses, respectively) was greater than that for the parent drug at both
      doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587947
TI  - Rat brain cytochrome P450. Reassessment of monooxygenase activities and
      cytochrome P450 levels.
AB  - There have been considerable interlaboratory variations in the reported levels of
      rat brain microsomal cytochrome P450 and associated monooxygenase activities. To
      ascertain if the variability could be accountable, at least in part, to different
      methodologies used for microsome preparation, cytochrome P450 monooxygenase
      components and activities were directly compared herein using brain microsome
      prepared by various methods. Rat brain microsome isolated using a calcium
      aggregation method in the presence of dithiothreitol and glycerol contained
      approximately 100 pmol of cytochrome P450/mg protein. Considerably lower
      cytochrome P450 levels (e.g. 20-40 pmol/mg protein) were found in brain microsome
      prepared in a more conventional manner using Tris or phosphate buffers without
      glycerol and dithiothreitol. The NADPH cytochrome c reductase activity was
      consistently approximately 23-25 nmol of cytochrome c reduced/min/mg protein,
      whatever the method of preparation of the brain microsome. Cytochrome P450
      associated monooxygenase activities, namely morphine N-demethylase and
      ethoxycoumarin O-deethylase, were dependent on the amount of protein in the
      incubation medium, the length of incubation, and the ratio of the concentration
      of the substrate to the amount of protein in the incubation mixture. The specific
      activity of morphine N-demethylase was constant over a range of protein
      concentration, if the ratio of the concentration of the substrate to the protein
      was kept constant.

PMID- 7587946
TI  - Regulation of the Ah gene battery via Ah receptor-dependent and independent
      processes in cultured adult rat hepatocytes.
AB  - A number of genes under the control of the arylhydrocarbon (Ah) receptor were
      tested for the effects of glucocorticoids on their expression in cultured primary
      rat hepatocytes. Treatment of cultured hepatocytes with 1.0 microM dexamethasone
      potentiated the induction (2- to 3-fold) of cytochrome P4501A1, glutathione S
      transferase Ya subunit (GSTYa), and UDP-glucuronosyltransferase gene expression
      by polycyclic aromatic hydrocarbons (PAH), whereas the glucocorticoid agonist
      suppressed PAH induction of NAD(P)H:quinone oxidoreductase (QOR) subunit and
      aldehyde dehydrogenase 3C gene expression by 60-80%. These results were seen at
      the level of enzyme activity for induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin
      and at the level of enzyme activity, protein, and specific mRNA for induction by
      1,2-benzanthracene. Two of these rat genes, GSTYa and QOR are also induced by
      electrophilic agents, such as t-butylhydroquinone. In the presence of t
      butylhydroquinone, dexamethasone caused a similar level of potentiation of GSTYa
      subunit expression and suppression of QOR subunit expression as was seen with the
      PAH, 1,2-benzanthracene. Studies using the glucocorticoid receptor antagonist,
      RU38486, demonstrated that the modulation of PAH induction by glucocorticoids of
      cytochrome P4501A1 and QOR activity is apparently dependent on action of the
      glucocorticoid receptor. These results suggest that the positive and negative
      changes observed are the result of specific alterations in the rates of
      transcription of these genes because of the action of the glucocorticoid
      receptor, thereby affecting regulation of GSTYa and QOR by both Ah receptor
      dependent and independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587948
TI  - Lymphatic distribution of 3'-azido-3'-deoxythymidine and 3'-azido-2',3'
      dideoxyuridine in mice.
AB  - Recently, it was shown that human immunodeficiency virus (HIV)-infected cells
      preferentially locate in lymphoid tissue early in the course of infection.
      Therefore, it is important to characterize the disposition of the anti-HIV
      agents, 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2', 3'-dideoxyuridine
      (AZdU), in the lymphatic system. The disposition of AZT and AZdU in serum and
      neck, axillary, and mesenteric lymph nodes was studied in mice after intravenous,
      oral, and intraperitoneal administrations of 50 mg/kg doses. Samples were
      collected at 0.08, 0.5, 1, 2, 3, 4, and 6 hr after dosing and nucleoside
      concentrations were determined by HPLC. Pharmacokinetic parameters were estimated
      using noncompartmental analysis. Maximum concentration, half-life, and area under
      the serum concentration vs. time curve (AUC) obtained from the serum
      concentration data were similar for both compounds after intravenous and
      intraperitoneal administrations; however, a difference in oral bioavailability
      for AZT and AZdU (49% and 76%, respectively) was noted. Patterns of regional
      distribution in lymph nodes were similar for both drugs; however, the
      accumulation of AZdU in the various lymph nodes, according to AUC values, was 3
      76% greater than that for AZT. The relative exposure re = AUClymph/AUCserum) of
      both nucleosides exhibited a dependence on route of administration. Intravenous
      and oral administrations resulted in a greater distribution of nucleoside into
      axillary lymph nodes, compared with neck and mesenteric lymph nodes. Following
      intraperitoneal administration, however, distribution was similar in all three
      regions. AZT and AZdU distribute into the lymphatic system; however, AZdU
      accumulation was greater than that of AZT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587949
TI  - Inhibition of (S)-warfarin metabolism by sulfinpyrazone and its metabolites.
AB  - Sulfinpyrazone markedly potentiates the anticoagulant effect of warfarin. The
      increased clotting time is accompanied by a marked decrease in the clearance of
      (S)-warfarin by virtue of a decrease in the P4502C9-catalyzed formation clearance
      to its major and inactive metabolite (S)-7-hydroxywarfarin. These data suggested
      that the mechanism of the drug interaction might be mediated through the
      inhibition of the catalytic activity of P4502C9 by sulfinpyrazone. However,
      initial human liver microsomal studies indicated that the in vitro Ki, for
      inhibition of (S)-7-hydroxywarfarin formation by sulfinpyrazone is at least 25
      fold higher than the therapeutic concentration of sulfinpyrazone in vivo. This
      result implied that other inhibitors probably contribute to the interaction.
      Kinetic studies conducted on sulfinpyrazone and two major metabolites,
      sulfinpyrazone sulfide and sulfinpyrazone sulfone, in microsomes prepared from
      three human livers give mean Ki's of 230 microM, 17 microM, and 73 microM
      respectively. Because sulfinpyrazone and its sulfide metabolite attain comparable
      plasma concentrations during the course of therapy, our inhibition results
      suggest that the sulfide metabolite is likely to be the primary species
      responsible for the inhibition of P4502C9-catalyzed formation of (S)-7
      hydroxywarfarin and the decrease in (S)-warfarin clearance in vivo.

PMID- 7587950
TI  - Increased blood and brain cocaine concentrations with ethanol cotreatment in
      mice.

PMID- 7587951
TI  - Computer prediction and experimental validation of cytochrome P4502D6-dependent
      oxidation of GBR 12909.

PMID- 7587952
TI  - Antipeptide antibodies against overlapping sequences differentially inhibit human
      CYP2D6.
AB  - Two peptides that correspond to sequences within the major 33-amino acid sequence
      recognized by human liver-kidney microsomal-1 autoantibodies were used to elicit
      antibodies in rabbits (four per peptide) against CYP2D6. Peptide
      1(DPAQPPRDLTEAFLA) corresponded to amino acids 263-277, and peptide 2
      (LLTEHRMTWDPAQPPRDLTE) corresponded to amino acids 254-273 of CYP2D6. The peptide
      keyhole limpet hemocyanin conjugates elicited good immune responses against their
      respective peptides as judged by enzyme-linked immunosorbent assay (titers of
      1/10,000 to 1/30,000). The antisera recognized CYP2D6 on Western blots and, to
      varying extents, inhibited recombinant CYP2D6 and liver microsomal CYP2D6
      activity. Immunization with peptide 2 produced antisera with the greatest
      inhibitory potency. Antiserum from a rabbit (#236) immunized with peptide 2
      inhibited up to 95% of dextromethorphan O-demethylase activity in human liver
      microsomes at the highest concentration tested (40% v/v) but did not
      significantly inhibit CYP1A2, CYP2C9, CYP2E1, or CYP3A4 marker activities. On
      Western blot, only a single immunoreactive protein comigrating with recombinant
      CYP2D6 was recognized. In liver microsomes from a CYP2D6-deficient individual, no
      proteins were recognized, and the antisera did not cross-react with recombinant
      CYP1A2, CYP2C9, CYP2E1, or CYP3A4. There was a significant correlation between
      the quantity of immunoreactive CYP2D6 as determined by immunoblotting with anti
      peptide 2 antiserum and dextromethorphan O-demethylation in a panel of 10 human
      liver microsomes (r = 0.95). These data identify a peptide sequence (peptide 2)
      that can be used to raise antisera that specifically recognize and inhibit
      CYP2D6.

PMID- 7587953
TI  - Pharmacokinetics of active drug metabolites after oral administration of perillyl
      alcohol, an investigational antineoplastic agent, to the dog.
AB  - The monocyclic terpene d-limonene, a major component in many citrus essential
      oils (1-3), has been used for many years as a flavoring agent, food additive, and
      fragrance (1, 2). It was recently demonstrated that limonene exhibits both
      chemopreventive and therapeutic effects against chemically induced mammary tumors
      in rats (4-10). Mechanistic studies revealed that limonene inhibits the
      posttranslational isoprenylation of 21-26 kDa cellular proteins implicated in
      cell growth and proliferation (11-13). Limonene is extensively metabolized by a
      variety of mammalian species (14-17). Its principal circulating metabolites
      identified in the rat, perillic acid and dihydroperillic acid, are also effective
      inhibitors of isoprenylation and cellular proliferation in vitro (17, 18).
      Furthermore, one of the metabolic precursors of these compounds, perillyl alcohol
      (16), is considerably more potent than limonene against the in vivo rat mammary
      tumor models (19). A preliminary report of an ongoing phase I clinical trial with
      limonene indicated that a single oral dose of 100 mg/kg is well tolerated (20).
      However, an extrapolation based upon the rat mammary tumor regression studies
      suggests that the minimum human dose requirement would be 1000 mg/kg/ day (6).
      The administration of such a large dose, which amounts to more than 80 ml of an
      oily volatile liquid, on a continuing basis may cause problems. Thus, perillyl
      alcohol is currently being developed as a clinical candidate at the National
      Cancer Institute because of its greater potency than limonene, which may enable
      potentially effective systemic concentrations of the active principals to be
      achieved at considerably lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587955
TI  - Species differences in the metabolism of a potent HIV-1 reverse transcriptase
      inhibitor L-738,372. In vivo and in vitro studies in rats, dogs, monkeys, and
      human.
AB  - In vivo and in vitro metabolism of 6-chloro-4(S)-cyclopropyl-3,4-dihydro-4-((2
      pyridyl) ethynyl)quinazolin-2(1H)-one (L-738,372), a potent human
      immunodeficiency virus-type 1 reverse transcriptase inhibitor, has been
      investigated in rats, dogs, and monkeys. Following 0.9 mg/kg iv and 9 mg/kg po
      doses, systemic blood clearance (CLB) and bioavailability (F) of L-738,372 were
      species-dependent and inversely related (CLB = 48, 15, and 3 ml/min/kg; F = 6, 62
      and 94%, in dogs, rats, and monkeys, respectively). Incubation of L-738,372 with
      rat liver slices and liver microsomes from all species studied led to the
      formation of two hydroxylated metabolites, M1 and M2. Kinetic studies of the
      microsomal metabolism of L-738,372 indicated that M1 was formed by a much higher
      affinity, but lower capacity enzyme(s) than that which catalyzed M2 formation in
      rats, dogs, and monkeys. The total intrinsic clearance of metabolite formation
      (CL(int) total = CL(int) M1 + CL(int) M2) was highest in dogs, followed by rats
      and monkeys. In dogs, CL(int) total was caused almost exclusively by CL(int) M1.
      Extrapolation of the CL(int) total values to the hepatic clearances (19, 8.4, and
      0.9ml/min/kg in dogs, rats, and monkeys, respectively) showed a similar rank
      order to the CLB observed in vivo. Good agreement between these in vivo and in
      vitro results suggests that the species differences in hepatic first-pass
      metabolism, and not the intrinsic absorption, contributed significantly to the
      observed differences in F.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587954
TI  - Xenobiotic-enhanced expression of cytochrome P450 2E1 and 2B1/2B2 in primary
      cultured rat hepatocytes.
AB  - Investigation of the posttranscriptional mechanisms involved in the xenobiotic
      mediated enhancement of cytochrome P450 2E1 (CYP2E1) expression has been limited
      by a lack of a functional primary hepatocyte cell culture system. We examined the
      effects of ciprofibrate (CIPRO) and pyridine (PYR) treatment on the expression of
      CYP2E1, P450 4A (CYP4A), and P450 2B (CYP2B) in primary rat hepatocytes cultured
      on Vitrogen or Matrigel substratum and in the presence of Chee's medium. Cells
      were cultured for 72 hr or longer before initiation of treatment. Northern blot
      analyses indicated that 24-hr CIPRO treatment enhanced the expression of CYP4A,
      and CYP2B mRNA in a concentration-dependent manner, with maximal induction of
      CYP2E1 mRNA (2- to 3-fold) and CYP4A1 mRNA (up to approximately 15-fold)
      monitored at 30-300 microM CIPRO. Maximal CYP2B mRNA levels (7- to 8-fold) were
      monitored at 300-1000 microM CIPRO. Treatment of hepatocytes for 24, 48, and 72
      hr with 30 microM CIPRO showed progressive increases in CYP2B and CYP4A mRNA
      levels, with approximately 13- and 60-fold elevations in the respective mRNAs
      occurring at 72 hr posttreatment. In contrast, CYP2E1 mRNA levels were maximally
      elevated between 2- and 3-fold at both 24 and 48 hr and were returning to basal
      levels by 72 hr. Western blot analyses revealed that 24-hr PYR (25 mM) treatment
      of CIPRO-treated cells, in the absence of any further increase in CYP2E1 mRNA
      levels, increased CYP2E1 protein levels approximately 6- to 8-fold. PYR treatment
      also increased CYP2B mRNA and CYP2B1/2B2 protein levels approximately 16-fold
      relative to cells treated only with CIPRO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587956
TI  - cDNA-directed expression of human cytochrome P450 CYP1A1 using baculovirus.
      Purification, dependency on NADPH-P450 oxidoreductase, and reconstitution of
      catalytic properties without purification.
AB  - A recombinant baculovirus containing the human cytochrome P450 (CYP) 1A1 cDNA was
      constructed and used to express CYP1A1 in Spodoptera frugiperda (SF9) insect
      cells (0.14 +/- 0.04 nmol/mg protein, 53 +/- 14 nmol/liter, N = 30). The enzyme
      represented approximately 1% of total cellular protein and was partially purified
      by a three-column procedure to a specific content of 5.0 nmol/mg protein.
      Catalytic activity was reconstituted with both the purified enzyme using lipid
      and NADPH-P450 oxidoreductase, and the SF9 insect cell membrane fraction without
      purification using NADPH-P450 oxidoreductase and small amounts of detergent.
      Catalytic activity of the enzyme after reconstitution was optimum using molar
      ratios of CYP1A1 to NADPH-P450 oxidoreductase of 1:8. Cytochrome b5 had no
      additional stimulating effect. The enzyme metabolized substrates characteristic
      for CYP1A1:benzo[a]pyrene (4.0 +/- 0.3 nmol/min/nmol CYP), 7-ethoxy-4
      trifluoromethyl- coumarin (36 +/- 2), ethoxyresorufin (37 +/- 1), but not
      pentoxyresorufin (0.77 +/- 0.02). Recombinant baculovirus expresses the highest
      amounts of all expression systems published to date of catalytically active
      CYP1A1. Because human CYP1A1 has never been isolated in a catalytically active
      state from human tissue, nor has recombinant unmodified human CYP1A1, this system
      is an excellent alternative for the isolation and characterization of this CYP.

PMID- 7587957
TI  - Characterization of the progesterone 21-hydroxylase activity of canine cytochrome
      P450 PBD-2/P450 2B11 through reconstitution, heterologous expression, and site
      directed mutagenesis.
AB  - Canine hepatic cytochrome P450 PBD-2 metabolizes 2,2',4,4',5,5'
      hexachlorobiphenyl and catalyzes the 21-hydroxylation of progesterone, thereby
      distinguishing PBD-2 as unique among 2B P450s. Heterologous expression of the PBD
      2 cDNA, P450 2B11, in COS and yeast systems produced a protein capable of
      androstenedione metabolism; however, this P450 did not metabolize progesterone in
      a manner consistent with PBD-2. Modification of PBD-2 reconstitution parameters
      resulted in significantly increased catalytic activities and further emphasized
      differences between PBD-2 and the heterologously expressed enzyme. Subsequent
      Escherichia coli expression of 2B11 generated a protein that possessed substrate
      specificities indistinguishable from those of PBD-2 and provided a system in
      which the determinants of 2B11 progesterone 21-hydroxylation could be examined
      via site-directed mutagenesis. Site-directed mutants of 2B11 expressed in E. coli
      revealed that substitution of Ile with Val at position 363 converted 2B11 into a
      highly active and specific progesterone 16 alpha-hydroxylase. Mutants Val-114 -->
      Ile, Asp-290 --> Ile, and Ile-365 --> Phe exhibited decreased progesterone 21-
      and 16 alpha-hydroxylase activities, in accordance with decreases in
      androstenedione hydroxylase activities. In contrast, replacement of Ile-365 with
      Val or Leu resulted in much greater changes in progesterone than androstenedione
      hydroxylation. Thus, the combination of P450 reconstitution techniques,
      heterologous expression, and site-directed mutagenesis has revealed PBD-2 to be
      an important progesterone 21-hydroxylase in canine liver and has identified
      several amino acid residues that alter progesterone metabolism by 2B11.

PMID- 7587958
TI  - Comparative ocular pharmacokinetics of brimonidine after a single dose
      application to the eyes of albino and pigmented rabbits.
AB  - Brimonidine is a potent ocular hypotensive drug. The ocular pharmacokinetics of
      14C-brimonidine in albino and pigmented rabbits were compared after ocular
      instillation of a 35-microliters drop of a 0.5% 14C-brimonidine solution. Ocular
      drug and metabolite concentrations were measured as total radioactivity and by a
      selective HPLC method. Rapid ocular absorption resulted in peak drug
      concentrations in aqueous humor of 2.16 +/- 0.75 micrograms/ml (mean +/- SD) and
      1.52 +/- 0.38 micrograms/ml at 0.67 hr postdosing in albino and pigmented
      rabbits, respectively. Drug elimination from aqueous humor was rapid initially
      with a half-life of 1 hr in rabbits, followed by a slower decline phase in
      pigmented rabbits. Radioactivity concentration in iris-ciliary body of albino
      rabbit reached a peak of 5.04 micrograms-eq/g at 40 minutes and declined to 0.10
      micrograms-eq/g at 6 hr postdosing with a half-life of 1 hr. The radioactivity
      concentrations in pigmented iris-ciliary body rose to a peak of 20.1 micrograms
      eq/g at 1.5 hr and stayed relatively steady for at least 4 hr before declining
      slowly to 0.43 micrograms-eq/g 90 days postdose. The terminal half-life of
      brimonidine in pigmented iris-ciliary body was 160 hr. Three metabolites were
      detected in the conjuctiva and iris-ciliary body, and brimonidine was the major
      drug-related substance in aqueous humor and iris-ciliary body. The results
      indicate that brimonidine is absorbed rapidly into rabbit eyes, metabolized in
      ocular tissues, and has significant affinity for melanin-containing
      tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587959
TI  - Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal
      administration in mice.
AB  - The pharmacokinetics of single intraperitoneal doses of paclitaxel (18 and 36
      mg/kg) in mice were investigated in the present study. The analysis of drug
      concentrations by HPLC indicated that the plasma Cmax (13.0 +/- 3.1 and 25.7 +/-
      2.8 micrograms/ml, respectively) were reached at the 2nd hr. The values of CL
      were low (0.06 and 0.1 ml/min, respectively), and t1/2 beta values of 3.0 and 3.7
      hr were found, after 18 and 36 mg/kg, respectively. The highest tissue
      concentrations were observed in the liver (50.2 +/- 3.1 and 92.0 +/- 9.5
      micrograms/g respectively), followed by the pancreas (39.3 +/- 9.9 micrograms/g)
      and the ovary (53.4 +/- 5.6 micrograms/g) after 18 and 36 mg/kg, respectively. In
      the case of the colic tissue, paclitaxel Cmax were 14.4 +/- 0.8 and 32.8 +/- 3.5
      micrograms/g at the 3rd hr, respectively, with sustained drug levels still
      detectable 24 hr after treatment. Paclitaxel Cmax values of 12.7 +/- 3.0 and 53.4
      +/- 5.6 micrograms/g were detected in the ovary after 18 and 36 mg/kg,
      respectively. The overall results provide evidence that, after intraperitoneal
      administration, paclitaxel concentrates in peritoneal organs; however, the
      intraperitoneal route does not prevent systemic drug exposure, allowing high and
      sustained levels of paclitaxel also in several extraperitoneal tissues.

PMID- 7587961
TI  - Microbial biotransformation of the angiotensin II antagonist GR117289 by
      Streptomyces rimosus to identify a mammalian metabolite.
AB  - Screening a range of microorganisms incubated with the angiotensin II antagonist
      GR117289 resulted in the use of Streptomyces rimosus to generate five related
      biotransformation products. These comprised three compounds hydroxylated on the
      aliphatic side chain, one further oxidized to a ketone, and one hydroxylated on
      the phenyl ring. These microbial metabolites were used as standards to identify a
      human metabolite detected in plasma and urine, but present in insufficient
      quantities for full structural characterisation. This further demonstrates how
      the use of microbial biotransformation systems at an early stage of drug
      metabolism studies can act as a valuable tool in facilitating identification of
      minor human metabolites.

PMID- 7587962
TI  - pH-dependent oral absorption of L-735,524, a potent HIV protease inhibitor, in
      rats and dogs.
AB  - L-735,524, a potent and specific inhibitor of human immunodeficiency virus
      protease, is currently under investigation for the treatment of acquired
      immunodeficiency syndrome. The aqueous solubility of L-735,524 was pH-dependent,
      > 100 mg/ml at pH below 3.5 and 0.03 mg/ml at pH 6. When L-735,524 was given
      orally as a suspension in 0.5% methocel (pH 6.5) at 10 mg/kg, the bioavailability
      was approximately 16% for both dogs and rats. When the same dose of the drug was
      administered in 0.05 M citric acid (pH 2.5), the bioavailability increased 4.5
      fold in dogs (72%), but only slightly in rats (24%). The pH- and species
      dependent differences in bioavailability observed in rats and dogs may be because
      of differences in the rate of gastric acid secretion and in the magnitude of
      hepatic first-pass effect. Gastric acid secretion is poor in dogs but substantial
      in rats. When L-735,524 was administered in 0.5% methocel, a large portion of the
      drug in dogs, but not in rats, remained undissolved, resulting in poor absorption
      in dogs. On the other hand, when L-735,524 was administered in citric acid, most
      of the drug would be in solution allowing for better absorption in dogs. The
      hypothesis of pH-dependent absorption was further supported by the findings that
      absorption was significantly increased in dogs after feeding, but substantially
      decreased in rats after pretreatment with famotidine, a potent H2-receptor
      antagonist. L-735,524 underwent an extensive first-pass metabolism in rats, but
      not in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587960
TI  - Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors,
      omeprazole and lansoprazole in rats.
AB  - The relationship between plasma concentrations and inhibitory effects on gastric
      acid secretion by omeprazole (OPZ) and lansoprazole (LPZ), which are used as
      antiulcer drugs in the clinical stage, was analyzed using the
      pharmacokinetic/pharmacodynamic (PK/PD) model in rats. After intravenous
      administration of OPZ and LPZ (1 mg/kg), OPZ was eliminated 1-exponentially and
      LPZ was eliminated 2-exponentially from plasma. Elimination was rapid with total
      body clearance of 57.6 ml/min/kg for OPZ and 58.6 ml/min/kg for LPZ. The volumes
      of distribution at steady-state were 0.66 liter/kg for OPZ and 1.04 liter/kg for
      LPZ, and the plasma unbound fractions were 0.105 and 0.069. The dose at which 50%
      of the maximum effect is elicited for the suppression of gastric acid secretion
      stimulated by histamine was 0.28 +/- 0.13 mg/kg (estimated value +/- SD) for OPZ
      and 0.18 +/- 0.03 mg/kg for LPZ. Second-order rate constants for association of
      OPZ or LPZ and H+,K+-ATPase based on a PK/PD model were 72.5 +/- 30.0 (estimated
      value +/- SD) and 124 +/- 58 ml/micrograms/hr respectively. Apparent turnover
      rate of H+,K+-ATPase was 8.8 hr as half-life, assuming the same value for both
      drugs. We concluded that pharmacokinetic elimination patterns of OPZ and LPZ were
      different, whereas the pharmacodynamic characteristics of both drugs are nearly
      the same in rats.

PMID- 7587963
TI  - Induction of liver microsomal cytochrome P450 in cynomolgus monkeys.
AB  - The aim of this study was to determine whether treatment of cynomolgus monkeys
      (Macaca fasicularis) with phenobarbital, beta-naphthoflavone, or dexamethasone
      causes an induction of microsomal crytochrome P450 (CYP) enzymes that are
      structurally and functionally related to rat enzymes belonging to the CYP1A,
      CYP2B, and CYP3A gene families. Oral treatment of male and female monkeys with
      phenobarbital resulted in a marked induction of a protein recognized by antibody
      against rat CYP2B1, as determined by Western immunoblotting. This protein,
      presumably a CYP2B enzyme, was not detectable in untreated monkeys, and was
      modestly inducible by dexamethasone but not beta-naphthoflavone. Induction of
      this CYP2B enzyme by phenobarbital was associated with a relatively large
      increase (up to 5-fold) in the rate of testosterone 16 beta-hydroxylation.
      Antibody, against rat CYP2B1 markedly inhibited this reaction in liver microsomes
      from phenobarbital-treated monkeys, but not from control monkeys. Consequently,
      the antibody-inhibitable rate of testosterone 16 beta-hydroxylation increased 17
      fold after treatment of monkeys with phenobarbital, which is comparable with the
      situation in rats. In contrast to the rat CYP2B enzymes, the monkey CYP2B enzyme
      had little or no capacity to convert testosterone to 16 alpha-hydroxytestosterone
      or androstenedione, and had negligible capacity to O-dealkylate 7
      pentoxyresorufin and 7-benzyloxyresorufin. Oral treatment of male and female
      monkeys with beta-naphthoflavone resulted in a marked induction of a protein
      recognized by polyclonal and monoclonal antibodies against rat CYP1A1 or against
      both CYP1A1 and CYP1A2. This protein was apparently a mixture of CYP1A1 and
      CYP1A2, neither of which was readily detectable in liver microsomes from control
      monkeys or monkeys treated with phenobarbital or dexamethasone. Induction of
      monkey CYP1A1/2 was associated with a marked increase in the O-dealkylation of 7
      methoxyresorufin (up to 65-fold), the O-dealkylation of 7-ethoxyresorufin (up to
      30-fold), and the N3-demethylation of caffeine (up to 17-fold), but only a 2-fold
      increase in benzo[a]pyrene 3-hydroxylation. Polyclonal antibodies against CYP1A1
      markedly inhibited the N3-demethylation of caffeine and the O-dealkylation of 7
      methoxy- and 7-ethoxyresorufin by liver microsomes from beta-naphthoflavone
      treated monkeys, and partially inhibited the 3-hydroxylation of benzo[a]pyrene,
      indicating that monkey CYP1A1 and/or CYP1A2, like the corresponding rat enzymes,
      can catalyze all four reactions. Treatment of monkeys with phenobarbital resulted
      in a 2- to 3-fold induction of a protein recognized by antibody against rat
      CYP3A1. This protein (CYP3A8 or an immunochemically related enzyme) was
      constitutively expressed in untreated monkeys of both sexes.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7587964
TI  - Stereoselectivity and isotope effects associated with cytochrome P450-catalyzed
      oxidation of (S)-nicotine. The possibility of initial hydrogen atom abstraction
      in the formation of the delta 1', 5-nicotinium ion.
AB  - The stereochemical course of cytochromes P450 [P4501A1, P4502B1, P4502B4, and
      P450101 (P450cam)] catalyzed alpha-carbon oxidations of the cis-(Z)- and trans
      (E)-5'-d1 diastereomers of (S)-nicotine has been examined. All enzyme
      preparations led to the stereoselective abstraction of the 5'-hydrogen atom trans
      to the pyridine ring with P450101 and human liver microsomal preparations
      displaying the highest (90%) and P4502B1 the lowest (67%) degree of
      stereoselectivity. No isotope effect was detected for any of the enzyme-catalyzed
      reactions, although the existence of an intrinsic isotope effect was inferred by
      the observation of an intramolecular isotope effect of 2-2.6 observed for the N
      demethylation of (S)-N'-dideuteromethylnornicotine. Evidence for P450101
      catalyzed N'-oxidation was sought but could not be found at higher than trace
      levels. These results, together with those obtained by computational methods, are
      interpreted in terms of an alpha-carbon oxidative pathway involving hydrogen atom
      abstraction rather than single electron transfer as the initiating event in the
      P450-catalyzed oxidation of (S)-nicotine to its delta 1',5'-iminium ion
      metabolite.

PMID- 7587965
TI  - Disposition and cardioselectivity of MDL 74,405, a vitamin E-like free radical
      scavenger, in rats and dogs after intravenous infusion.
AB  - The disposition kinetics of MDL 74,405, a potent free radical scavenger for
      cardiac reperfusion and a vitamin E analog, was investigated in rats (1.2, 6.0,
      and 12 mg/kg) and dogs (1 and 10 mg/kg) after an intravenous infusion. Because
      the heart is the target site of drug action, a tissue distribution study was also
      conducted in rats (1.2 mg/kg) to explore the affinity of the drug to rat heart.
      In both animal species, plasma drug concentrations declined rapidly in the early
      distribution phase and exhibited a multiexponential pattern of elimination. Of
      the total excretion (95-96% of the dose) in 120 hr in rats, 45-51% was excreted
      in urine and 45-50% in feces. Of the total excretion (86-89% of the dose) in 120
      hr in dogs, 41-43% of the dose was excreted in urine and 41-43% in feces. The
      dose was excreted mainly unchanged (62-78% in rat and 80-86% of the dose in dog
      urine) with several potential minor metabolites, indicating that renal and
      biliary excretions are the two major, equally important, routes of drug
      elimination in both species. Rats cleared the drug from the body markedly faster
      than dogs: the mean residence time in rats. (1.9-3.2 hr) was 15-20 times shorter,
      the terminal elimination half-life in rats (3.6-7.0 hr) was 10 times shorter; and
      the total clearance in rats (148-216 ml/min/kg) was 6-9 times greater. The steady
      state volume of distribution was very large for both species. (19-37 liters/kg
      for rats and 59-64 liters/kg for dogs), which is consistent with the extensive
      tissue uptake of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587966
TI  - In vitro metabolism of terfenadine by a purified recombinant fusion protein
      containing cytochrome P4503A4 and NADPH-P450 reductase. Comparison to human liver
      microsomes and precision-cut liver tissue slices.
AB  - The metabolism of terfenadine was studied with a cDNA-expressed/purified
      recombinant fusion protein containing human liver microsomal cytochrome P4503A4
      (CYP3A4) linked to rat NADPH-P450 reductase (rF450[mHum3A4/mRatOR]L1) and was
      compared with that observed in the presence of human liver microsomes and
      precision-cut human liver tissue slices. In all three cases, [3H]terfenadine was
      metabolized to at least three major metabolites. LC/MS (electrospray) analysis
      confirmed that these metabolites were alpha, alpha-diphenyl-4-piperidinomethanol
      (M5), t-butyl hydroxy terfenadine (M4), and t-butyl carboxy terfenadine (M3),
      although the level of M5 detected in the presence of fusion protein was greater
      than that found with microsomes or tissue slices. Two additional metabolites, M1
      (microsomes and tissue slices) and M2 (fusion protein), were also detected, but
      remain uncharacterized. Consumption of parent drug (microsomes: KM = 9.58 +/-
      2.79 microM, Vmax = 801 +/- 78.3 pmol/min/nmol CYP; fusion protein: KM = 14.1 +/-
      1.13 microM, Vmax = 1670 +/- 170 pmol/min/nmol CYP) and t-butyl hydroxylation to
      M4 (microsomes: KM = 12.9 +/-3.74 microM, Vmax = 643 +/- 62.5 pmol/min/nmol CYP,
      ; fusion protein: KM = 30.0 +/- 2.55 microM, Vmax = 1050 +/- 141 pmol/min/nmol
      CYP) obeyed Michaelis-Menten kinetics over the terfenadine concentration range of
      1-200 microM. Ketoconazole, a well-documented CYP3A inhibitor, effectively
      inhibited terfenadine metabolism in all three models. The conversion of M4 to M3,
      studied with human liver microsomes and fusion protein, was NADPH-dependent and
      inhibited by ketoconazole. It is concluded that cDNA-expressed CYP3A4, in the
      form of a NADPH-P450 reductase-linked fusion protein, may also serve as a model
      for studying the metabolism of terfenadine in vitro and many other drugs.

PMID- 7587968
TI  - Withdrawal-like effects of pentylenetetrazol and valproate in the naive organism:
      a model of motivation produced by opiate withdrawal?
AB  - Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive
      rat various behavioural effects resembling signs of opiate withdrawal in the
      morphine-treated subject. Suggestions in the literature that these substances may
      activate directly some of the neural consequences of opiate and drug withdrawal
      prompted us to look for and examine possible aversive effects of these substances
      at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion
      procedure, relatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do
      indeed have aversive effects. The maximum aversions were produced by 10 and 20
      mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of morphine withdrawal
      precipitated by 0.01-0.03 mg/kg naloxone in a morphine pellet-implanted animal.
      Moreover, the maximum aversions with PTZ and VPA were significantly higher than
      the maximum aversions seen with naloxone in the drug-naive animal under the same
      training conditions. Thus, the data from the present study confirmed the notion
      that low doses of PTZ and VPA in the naive animal may activate processes
      activated by drug withdrawal, including those important for the motivational
      effect of withdrawal. However, it was also pointed out that the lowest dose VPA
      producing aversion was higher than that found here to produce writhes and ataxia
      (80 mg/kg) but the same as that required for shaking (160 mg/kg), while the PTZ
      aversion was at a dose lower than that known to produce a PTZ cue. Implications
      were discussed for using withdrawal-like phenomena as a model in the non-treated
      organism of clinically-relevant withdrawal effects.

PMID- 7587967
TI  - Interspecies scaling of a thienodiazepine platelet-activating factor receptor
      antagonist.

PMID- 7587969
TI  - Cognitive capacity in female adolescent substance abusers.
AB  - Female adolescents who qualified for a DSM-III-R diagnosis of psychoactive
      substance use disorder (n = 106) were compared to normal controls (n = 74) on a
      battery of cognitive, intellectual and achievement tests. It was found that the
      substance abuse group performed deficiently on tests requiring language skills,
      sustained attention and perceptual efficiency and scored lower than controls on
      standardized tests of intelligence and academic achievement. No relationship
      between magnitude of cognitive deficit and severity of substance abuse was
      observed. The implications of these findings are discussed with respect to the
      etiology and maintenance of drug use.

PMID- 7587970
TI  - Cytokine levels in acute alcoholic hepatitis: a sequential study.
AB  - Chronic alcoholic liver disease is associated with several immunological
      alterations: depressed T-cell function, low serum gamma-interferon, and high
      serum tumour necrosis factor (TNF-alpha) and interleukin levels. Therefore,
      macrophage activity seems to be enhanced. Some cytokines, such as TNF-alpha,
      exert adverse effects on chronic alcoholic liver disease, so that protracted
      activation of macrophages with continuous TNF-alpha production may aggravate
      alcoholic hepatitis. Based on these facts we have sequentially determined serum
      levels of TNF-alpha, 1 beta interleukin (IL-1 beta), gamma-interferon and
      neopterin--a macrophage product--at admission, and at the end of the first, third
      and sixth weeks after admission, of 43 patients affected by alcoholic hepatitis,
      and of 20 age-matched sanitary workers as controls. Our patients showed higher
      levels of neopterin and lower levels of IL-1 beta and gamma-interferon than the
      controls; TNF-alpha levels in our patients were almost significantly higher than
      in controls. TNF-alpha levels at admission were higher in the patients who died
      (P = 0.025). TNF-alpha and neopterin levels showed no trend to normalization in
      patients who died, with higher levels of neopterin at first and third weeks and
      higher TNF-alpha and gamma-interferon levels at first week. Using logistic
      regression analysis, serum TNF-alpha levels at admission showed significant (P =
      0.045), independent effects on mortality, as well as serum neopterin (P = 0.0026)
      at the first week. Thus, enhanced macrophage activity, measured by serum levels
      of TNF-alpha and neopterin seems to be related to a worse prognosis in alcoholic
      hepatitis.

PMID- 7587971
TI  - Cannabis use in a drug and alcohol clinic population.
AB  - Cannabis using behaviour was determined, by structured interview, in 100
      consecutive clinic attenders who had used cannabis within 28 days. Subjects were
      white, 85 were male, mean age was 27.6 years and duration of cannabis use was
      12.4 years. The mean consumption of the past week was 10.5 g. Sixty percent
      smoked daily. The average cannabis cigarette comprised three cigarette papers,
      the tobacco from three-quarters of a king sized cigarette, and 0.35 g of cannabis
      resin. Eating cannabis was unusual. Fifty subjects had a conviction for
      possession of cannabis. Subjects fulfilled criteria for 'heavy' use. The findings
      are discussed in the context of previous research.

PMID- 7587972
TI  - Decrease in alcohol tolerance: clinical significance in alcohol dependence.
AB  - In 237 male inpatients with alcohol dependence, clinical, demographic and
      biochemical data were analyzed in relation to alcohol tolerance. All subjects had
      a history of marked tolerance. At the time of assessment, 46% of subjects
      continued to meet the criteria for marked tolerance and 54% of the subjects
      reported a loss or decreased tolerance. Subjects with decreased tolerance were
      older than those with high tolerance and had a longer duration of illness. The
      age of onset was similar in both groups. Patients with decreased tolerance had
      more mental confusion and psychotic symptoms, and were less likely to be
      currently married.

PMID- 7587973
TI  - The Alcohol Use Disorder and Associated Disabilities Interview schedule
      (AUDADIS): reliability of alcohol and drug modules in a general population
      sample.
AB  - Using a representative sample of the general population, the test-retest
      reliability of the alcohol and drug modules of the Alcohol Use Disorder and
      Associated Disabilities Interview Schedule (AUDADIS) was examined. The AUDADIS
      showed good to excellent reliability for measures of alcohol consumption and use
      of sedatives, tranquilizers, amphetamines, opioids (other than heroin), cannabis
      and cocaine. Equally good reliability was demonstrated for diagnoses of alcohol,
      cannabis, cocaine and heroin abuse or harmful use and dependence defined in terms
      of the International Classification of Diseases-Tenth Revision (ICD-10) and the
      Diagnostic and Statistical Manual of Mental Disorders-Third Edition-Revised (DSM
      III-R) and Fourth Edition (DSM-IV). Results are discussed in terms of the need
      for future research on the psychometric properties of the AUDADIS in clinical and
      general population samples.

PMID- 7587974
TI  - Stages and processes of change among polydrug users in methadone maintenance
      treatment.
AB  - We applied the stages-of-change model of Prochaska and DiClemente to the problem
      of drug use among methadone maintenance patients to examine correlates of
      different stages of treatment readiness. The 276 subjects were divided into stage
      categories based on self-reported drug use and questionnaire responses regarding
      plans to discontinue unauthorized drug use in the future. Confirmatory factor
      analytic procedures validated four process scales derived from a 60-item
      questionnaire. Each stage was characterized by a profile of change-process scores
      largely consistent with predictions, though these scores did not distinguish
      stages as clearly as has been reported in previous research. Analysis of subject
      characteristics revealed that those in the Precontemplation stage reported
      significantly longer treatment tenures than subjects in any other stage besides
      Maintenance.

PMID- 7587975
TI  - Absence of acute cocaine interactions with the MAO-B inhibitor selegiline.
AB  - Selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor, is under
      investigation as a treatment for cocaine relapse prevention. To evaluate its
      safety, human volunteers (n = 5) received intravenous cocaine (0, 20 and 40 mg, 1
      h apart) following treatment with placebo or selegiline (10 mg, p.o.). Cocaine
      increased heart rate, blood pressure, pupil diameter and subjective indices of
      euphoria and craving. Selegiline produced no measureable effects, except for
      miosis, and did not alter the effects of cocaine. These data suggest that
      selegiline may be safely administered in combination with cocaine, and that
      selegiline is unlikely to increase reinforcing effects of cocaine.

PMID- 7587976
TI  - Flunitrazepam and nordiazepam slowly released from silastic capsules induce
      physical dependence in rat.
AB  - The rates of in vitro release of flunitrazepam (FN), nordiazepam (ND) and
      diazepam (DZ) from silastic capsules were compared and found to be in the
      following order: DZ > FN > ND. Rats that were implanted subcutaneously with
      capsules filled with FN or ND for 5 to 7 weeks before administering flumazenil
      (FLU) (40 mg/kg, i.v.) showed precipitated abstinence as measured by the
      Precipitated Abstinence Score (PAS) which included a rapid onset of clonic and
      tonic-clonic convulsions. Rats implanted with DZ also demonstrated significant
      PAS and seizures. Implantation of similar doses of DZ, FN and ND resulted in
      different plasma levels of parent benzodiazepines and their metabolites that
      corresponded with their in vitro release: DZ > FN > ND. These data indicate that,
      as for DZ, the capsule implantation is an effective method of producing physical
      dependence on FN and ND in the rat.

PMID- 7587979
TI  - Who needs nine ACE inhibitors?

PMID- 7587978
TI  - The treatment mapping survey; a descriptive study of drug and alcohol treatment
      responses in 23 countries.
AB  - This WHO key informant survey looked at services for the treatment of drug and
      alcohol problems in 23 different countries. Not surprisingly, there were many
      differences between treatment responses in the different countries. However, the
      survey also revealed many similarities in treatment responses. Most countries are
      confronted by problems of scarcity of resources for substance abuse treatment and
      many countries also noted the inadequate levels of staff training. Treatment was
      often primarily delivered in a non-residential setting (especially for alcohol
      problems). However, some countries treated drug and alcohol problems mainly in
      residential or inpatient settings. Psychiatrists were one of the professional
      groups most frequently involved in treatment, and the psychiatric hospital is one
      of the most common treatment locations. Most key informants reported a lack of
      basic information about the effectiveness of particular treatment interventions
      and treatment programmes. Drug services and alcohol treatment services were
      generally integrated in terms of staff, location, or treatment programmes and in
      some countries this integration was a feature of the national treatment system.
      Sometimes the integration of drug and alcohol treatment services was due to the
      scarcity of national treatment resources. Not all countries operated an
      integrated drug and alcohol treatment system. In several countries drug and
      alcohol treatment services were usually provided separately, and a number of
      countries expressed a preference for this independence. Countries also differed
      in the extent to which they provided drug or alcohol treatment in conjunction
      with other health care services with about half of the countries operating with
      close links with health care services and the other half operating largely
      independently.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7587981
TI  - Management of patients with thrombophilia.

PMID- 7587982
TI  - Management of acute otitis media and glue ear.

PMID- 7587983
TI  - Dornase alfa for cystic fibrosis.

PMID- 7587977
TI  - Features of cocaine dependence with concurrent alcohol abuse.
AB  - In order to assess differences between cocaine dependence alone and cocaine
      dependence complicated by alcohol abuse, 34 subjects who met DSM-III-R criteria
      for alcohol abuse and cocaine dependence (COC-ETOH group) were compared with 39
      subjects who met criteria for cocaine dependence only (COC-only group) with
      regard to demographics, substance use, and psychopathology. There were no
      differences between groups in age, race, employment or socio-economic status. The
      baseline depression and global severity scores in the COC-ETOH group were
      significantly higher than in the COC-only group. The COC-ETOH group was
      significantly more likely to experience a paranoid psychosis with cocaine use and
      significantly more likely to have abused additional substances in the month prior
      to study entry. The COC-ETOH group also attended significantly fewer medication
      management sessions during the 12-week trial. There were no differences between
      groups in the type or frequency of Axis 1 or Axis II disorders.

PMID- 7587984
TI  - Diagnosis and treatment of streptococcal sore throat.

PMID- 7587980
TI  - Drugs for the doctor's bag.

PMID- 7587985
TI  - Methotrexate for rheumatoid arthritis.

PMID- 7587986
TI  - Finasteride and benign prostatic hyperplasia.

PMID- 7587988
TI  - Antibiotic-induced diarrhoea.

PMID- 7587989
TI  - Magnesium, myocardial infarction, meta-analysis and megatrials.

PMID- 7587987
TI  - Once-a-day topical corticosteroids.

PMID- 7587990
TI  - Drug-resistant tuberculosis.

PMID- 7587992
TI  - Risk:benefit analysis of drugs in practice. The doctor, the patient and the
      licensing authority.

PMID- 7587994
TI  - Zolpidem--a hypnotic with a difference?

PMID- 7587991
TI  - Dopexamine after cardiac surgery.

PMID- 7587993
TI  - Lansoprazole--another proton pump inhibitor.

PMID- 7587996
TI  - Managing acute pain in children.

PMID- 7587997
TI  - Allergen testing in patients with type I hypersensitivity.

PMID- 7587995
TI  - Carvedilol for hypertension.

PMID- 7587998
TI  - Selective serotonin reuptake inhibitors in obsessive-compulsive disorder.

PMID- 7588000
TI  - Managing chronic pain in children.

PMID- 7587999
TI  - Drugs for Parkinson's disease reviewed.

PMID- 7588001
TI  - Drugs for the doctor's bag--you respond.

PMID- 7588002
TI  - New drugs for hyperprolactinaemia.
AB  - In 1976 we heralded the introduction of bromocriptine (Parlodel-Sandoz) as "an
      important advance" for the treatment of patients with hyperprolactinaemia. Now
      two new drugs are available for treating hyperprolactinaemia; cabergoline
      (Dostinex-Pharmacia) which the manufacturer claims offers "a significant advance
      in prolactin control" and quinagolide (Norprolac-Sandoz) for which the claim is
      of a "significant advance in the therapy of hyperprolactinaemia". Do these newer
      products hold real advantages?

PMID- 7588003
TI  - Articular and periarticular corticosteroid injections.
AB  - Intra-articular and soft tissue injections of corticosteroid are widely used in
      the treatment of patients with rheumatic disorders. Hydrocortisone acetate, which
      was the first to be used, was introduced over forty years ago. Several synthetic
      corticosteroids followed: but critical comparisons of the different
      corticosteroid preparations were few and inconclusive when we last reviewed them.
      In this article we consider the preparations, when they help, who should give
      them, their risks and the precautions necessary.

PMID- 7588004
TI  - In-vitro activity of antibacterial drugs and clinical practice.
AB  - Before prescribing an antibiotic, treatment guidelines usually suggest that a
      specimen containing the suspected organism is sent for culture and sensitivity.
      Microbiology departments, for their part, use in-vitro sensitivity of isolates
      taken from patients with bacterial infections to recommend which antibiotic(s) to
      use in the patients themselves or as a guide to empirical treatment in others. In
      this article we consider the value of in-vitro testing to clinical practice.

PMID- 7588006
TI  - [Metastasizing pancreatic vipoma. Its diagnosis and therapy with the somatostatin
      analog octreotide].
AB  - HISTORY: An 82-year-old woman was hospitalized for anaemia of 4.8 g/dl after
      having suffered for about one year from watery treatment-resistant diarrhoea,
      causing a weight loss of ca. 10 kg. FINDINGS: Computed tomography, magnetic
      resonance imaging and endosonography revealed a 2.5 x 2.0 cm space-occupying mass
      in the body of the pancreas. Taking into account electrolyte abnormalities
      (potassium 2.7 mmol/l), marked metabolic acidosis (pH 7.16, base excess -20.3
      mmol/l) and achlorhydria, an increased serum concentration of vasoactive peptide
      (VIP) of 548.5 pmol/l confirmed a VIPoma. Somatostatin-receptor scintigraphy also
      demonstrated a metastasis, 1.8 cm in diameter, in the region of the right ovary.
      TREATMENT AND COURSE: Under administration of somatostatin analogue octreotide
      (150 micrograms three times daily subcutaneously) the symptoms quickly
      disappeared and the stools as well as electrolyte and acid-base balances became
      normalized. After 5 months of treatment the levels of VIP, pancreatic enzymes and
      gastrin were within normal limits or clearly suppressed. There has been no recent
      evidence of tumour progression. CONCLUSION: This case demonstrates so far
      successful suppression of a metastasizing VIPoma with the somatostatin analogue
      octreotide, the metastasis having been revealed first by somatostatin-receptor
      scintigraphy.

PMID- 7588005
TI  - [The risk assessment of the need for help and care as well as the risk of
      mortality among older people. The results of an 18-month pilot study in a family
      practice].
AB  - OBJECTIVE: To investigate prospectively the prognostic power of various
      demographic and diagnostic parameters, as well as of medical history, for
      evaluating in elderly patients the probability of their requiring care and of
      their risk of dying soon. PATIENTS AND METHOD: All the elderly patients (> or =
      70 years) of one general practitioner were included. Of 178 patients who
      fulfilled the inclusion criteria, 144 participated (93 women, 49 men; mean age
      78.7 +/- 5.8 years). Demographic, basic diagnostic and medical history data of
      the kind that can be easily collected in general practice were recorded. The
      general practitioner was also asked to assess the probability of each patient
      requiring care and the likelihood of their dying soon. Several functional tests
      that record or measure daily activity were conducted. After 18 months all
      admissions to care, homes for the elderly or hospital and deaths were recorded.
      The different groups were compared. RESULTS: The probability of requiring care
      and of dying within the observation period were predicted more accurately by
      functional tests and questions than by conventional diagnostic methods. This was
      particularly so for functional investigations of basic daily activity, cognitive
      ability and manual skills. There were significant differences between the groups
      in the results of tests (P < 0.01). CONCLUSION: Functional tests can be rapidly
      performed and have high diagnostic and prognostic power. They are therefore
      recommended for use by general practitioners for assessing the probability of a
      given patient requiring care and for estimating the likelihood of early death.

PMID- 7588008
TI  - [Complications in preclinical resuscitation].

PMID- 7588007
TI  - [Neurological symptoms after an infection by the sandfly fever virus].
AB  - CASE 1: A few days after returning from a holiday in Italy a 50-year-old man
      developed acute gastrointestinal symptoms, followed by headache, fever and joint
      pains. After transitory remission he had a relapse with fever, headache and
      meningitis 2 weeks later. Cerebrospinal fluid contained gram-negative diplococci,
      but no bacteria grew on culture. Under the suspected diagnosis of meningitis he
      was treated with penicillin. Ten days later he suddenly developed deafness in his
      right ear. The various signs and symptoms gradually disappeared and the patient
      was discharged after 24 days in hospital. Retrospectively serological tests
      indicated sandfly fever (SF) virus infection with serotype Toscana. This is
      thought to be the first reported case of deafness associated with this disease.
      CASE 2: One week after returning from a holiday in Tunisia a 34-year-old man fell
      ill with fever, headache, rigor, nausea, joint pains and a maculopapular rash for
      which he was treated as an outpatient. The symptoms improved after 7 days, except
      for the headache which persisted another 5 days. Serology demonstrated an acute
      infection by SF virus, serotype Sicilian. CONCLUSION: Sandfly fever should be
      included in the differential diagnosis of headache, fever and signs of meningitis
      in persons who have recently been to mediterranean countries.

PMID- 7588009
TI  - [Systemic amyloidosis. Its pathogenesis, clinical picture and therapy].

PMID- 7588010
TI  - [Vitamin E].

PMID- 7588011
TI  - [A causal relationship between a collision and an intervertebral disk prolapse?].

PMID- 7588012
TI  - [Ulcerative colitis as the primary manifestation of the Churg-Strauss syndrome].

PMID- 7588015
TI  - [Transurethral prostatic resection or observation of the course of benign
      prostatic hyperplasia?].

PMID- 7588013
TI  - [Ulcerative colitis as the primary manifestation of the Churg-Strauss syndrome].

PMID- 7588016
TI  - [Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not colonic
      Crohn's disease].

PMID- 7588017
TI  - [The association of young maternal age and the birth of underweight and premature
      children].

PMID- 7588014
TI  - [Budesonide].

PMID- 7588019
TI  - [Intestinal angiodysplasias as initially unrecognizable cause of recurrent
      gastrointestinal hemorrhage].
AB  - HISTORY AND CLINICAL FINDINGS: Five years before hospitalization a 72-year-old
      woman was first found to have anaemia. Shortly thereafter she had noticed blood
      on her stool, but endoscopy had failed to find the origin of the bleeding.
      Selective mesenteric angiographies, diagnostic laparoscopy and contrast
      radiography of the small intestine (after Sellink) as well as scintigraphy during
      the subsequent years had all been negative, although there had been several
      severe bleedings. Admission was prompted by renewed severe peranal blood loss.
      The patient was found to be obese but in a poor general state. Her skin was pale,
      blood pressure was 80/60 mmHg, heart rate 130/min. The abdomen was soft and
      without resistance on palpation. INVESTIGATIONS: Haemoglobin was 5.7 g/dl,
      haematocrit 26%. Quick value, partial thromboplastin time and prothrombin time
      were normal. Emergency esophagogastroduodenoscopy and coloscopy as well as
      angiography again failed to find the source of bleeding. TREATMENT AND COURSE:
      The circulation was stabilized with infusion of 4 units of erythrocyte
      concentrate and 2000 ml 10% hydroxyethylstarch. The blood pressure again dropped
      2 days later. In parallel to renewed volume substitution another angiography was
      performed. This revealed arteriovenous shunts with ectasias in the terminal
      ileum. A right hemicolectomy was performed. The resected specimen showed
      intestinal angiodysplasia. At follow-up 6 months later the patient was symptom
      free and there had been no further bleeding. CONCLUSION: Even selective
      angiography of the superior mesenteric artery sometimes fails to demonstrate
      intestinal angiodysplasia. The diagnosis may then be made by repeat angiography
      during the phase of acute bleeding.

PMID- 7588018
TI  - [Acute myocardial ischemia in spontaneous coronary artery spasm].
AB  - AIM OF STUDY: To discover what factors indicate spontaneous coronary artery
      spasms as a cause of myocardial ischaemia. PATIENTS AND METHOD: In a
      retrospective analysis 15 of 1407 consecutive patients who had undergone coronary
      arteriography (six women and nine men; mean age 47 +/- 11 years) had acute
      ischaemia due to spontaneous coronary artery spasms. The clinical findings at the
      time of first investigation and during the follow-up period (mean of 29 [3-65]
      months) were evaluated. RESULTS: The most common risk factors were
      hypercholesterolaemia (> or = 200 mg/dl) in ten patients (66%) and heavy nicotine
      consumption > or = 20 cigarettes per day) in eight patients (55%). Of the
      patients with angina at rest nine had reversible ST elevations, six had terminal
      T negativity in the ECG and an increased incidence of ventricular arrhythmias (n
      = 6). At time of hospitalization ten patients had acute myocardial ischaemia and
      five had signs of acute myocardial infarction (maximal creatine kinase
      concentration: 121-2980 U/l). Acute coronary angiography revealed circumscribed
      coronary artery constriction, reversible with nitroglycerin, with stenosis of <
      70% in five patients and of > or = 70% in six, as well as intermittent vessel
      occlusion in four patients. Angiography showed smooth coronary artery walls in
      almost all instances. Angiographic evidence of circumscribed arteriosclerotic
      lesion with maximally 50% narrowing was present in six patients. CONCLUSION:
      Especially in younger, male patients with hypercholesterolaemia and heavy smoking
      recurrent anginal pectoris at rest, with reversible ECG signs of myocardial
      ischaemia but without advanced coronary sclerosis, speaks for spontaneous
      coronary artery spasms as the cause.

PMID- 7588022
TI  - [Pregnancy in essential thrombocythemia. Manifestation time and risk for mother
      and child].

PMID- 7588023
TI  - [Honorarium sharing between the radiologists and transit physicians. Decision of
      the Higher Regional Court, Hamm, January 16, 1995].

PMID- 7588021
TI  - [Active vaccinations in multiple sclerosis].

PMID- 7588020
TI  - [Phenprocoumon-induced cholestatic hepatitis].
AB  - HISTORY AND CLINICAL FINDINGS: A 78-year-old woman had 4 years age received
      phenprocoumon as prophylaxis against thromboembolism after implantation of a left
      total knee prosthesis. Ten weeks later she developed hepatitis with negative
      hepatitis serology. 6 weeks before her latest hospitalisation a right total knee
      implantation had been performed and she again received phenprocoumon. She was
      admitted now because of cholestatic jaundice with rapid deterioration of her
      general state. There were no significant abnormal findings other than jaundiced
      skin and sclerae. INVESTIGATION: Bilirubin concentration was clearly elevated to
      11.5 mg/dl, and the transaminase activities were increased, together with raised
      gamma-GT and alkaline phosphatase levels. The Quick value was below 8%. Hepatitis
      serology was positive for hepatitis A antibodies, but negative for B and C
      antibodies. No antigens were demonstrated. The eosinophil count was elevated in
      the differential blood count. Sonography showed a normal-sized liver with
      slightly dense echo pattern, but no evidence of abscess or dilatation of the bile
      duct system. Liver biopsy revealed severe acute hepatitis of viral type and
      discrete eosinophilic infiltration. TREATMENT AND COURSE: After all medication
      had been discontinued, transaminase activities decreased while bilirubin
      concentration rose. Thus, prednisone treatment was started (initially 50 mg/d),
      the dose then gradually reduced. The cholestasis parameters became normal and the
      patient's general state was much improved so that she could be discharged.
      CONCLUSION: Cholestatic hepatitis is a rare side effect of phenprocoumon. The
      associated eosinophilia suggests the cause to be an allergic genesis in the sense
      of a hypersensitivity reaction.

PMID- 7588024
TI  - [Treatment of myelodysplastic syndromes aside from clinical studies].

PMID- 7588026
TI  - [Phenprocoumon-induced necrotizing hepatitis].

PMID- 7588027
TI  - [Time interval between coloscopy with biopsy and colonic contrast enema].

PMID- 7588028
TI  - [Sleep-related breathing disorders in patients with coronary heart disease].
AB  - INTRODUCTION AND AIM OF STUDY: Obstructive sleep apnoea (OSA) favours the
      development of arterial hypertension independently of body-weight and may thus
      have an effect on coronary heart disease (CHD). This study was undertaken to
      determine the prevalence of OSA in patients with CHD. PATIENTS AND METHODS: From
      among all patients in whom left heart catheterization with coronary angiography
      had provided the diagnosis of coronary heart disease 50 were randomly chosen (47
      men, 3 women; mean age 61 +/- 6 years) for further investigations. During the
      night airway flow, heart rate, body position and arterial oxygen saturation were
      recorded. The patients also had to fill in a questionnaire concerning tiredness
      during the day and any snoring. Polysomnography was performed in all those whose
      apnoea index (AI) was > 10/h. RESULTS: 25 patients had an apnoea index of > 10/h.
      Eight of them also had increased tiredness during the day. The patients with an
      AI > 10/h were significantly older than those in whom it was < or = 10/h (63.1 +/
      3.5 vs 58.4 +/- 7.2 years; P < 0.002) and also had a higher body-mass index
      (27.8 +/- 4.2 vs 25.7 +/- 3.0 kg/m2; P < 0.05). Polysomnography, done in the
      sleep laboratory, in 19 of the 25 patients with an AI > 10/h registered an
      average AI of 17.0 +/- 10.9 per hour sleep; in seven patients it was > 20/h.
      CONCLUSIONS: The prevalence of obstructive sleep apnoea (OSA) is higher in
      patients with coronary heart disease (CHD) than in the healthy population. As OSA
      associated with a marked fall in nocturnal blood oxygen saturation and a rise in
      blood pressure may cause myocardial ischaemia, OSA should also always be
      considered when CHD is diagnosed.

PMID- 7588029
TI  - [Radiofrequency ablation in permanent ectopic left atrial tachycardia].
AB  - HISTORY AND FINDINGS: A 35-year-old symptom-free woman was known since childhood
      to have an increased resting heart rate (130-150/min). In the ECG there was a
      negative P in leads I and aVL, with a shortened P-Q interval of 90 ms. Previous
      treatment with beta-receptor blockers and calcium antagonists had failed.
      Clinical examination and echocardiography, as well as levels of thyroid hormone
      were unremarkable. During electrophysiological studies the earliest atrial
      activity was localised by endocardial leads in the region of the distal coronary
      sinus and the arrhythmia could not be terminated by atrial over-stimulation.
      TREATMENT AND COURSE: After transseptal puncture the ablation catheter was
      introduced into the left atrium and, the exact site of the origin of the atrial
      tachycardia having been established, radiofrequency ablation of this point was
      successfully performed. Subsequently the patient was always found to be in stable
      sinus rhythm at around 80/min. CONCLUSION: To prevent tachycardia-induced
      cardiomyopathy, radiofrequency ablation can be indicated even in symptom-free
      patients with atrial tachycardia.

PMID- 7588025
TI  - [Tissue plasminogen activator after resuscitation in fulminant pulmonary
      embolism].

PMID- 7588030
TI  - [Endemic sprue: its first diagnosis based on bleeding complications].
AB  - HISTORY AND CLINICAL FINDINGS: A 47-year-old man without previously known illness
      was admitted to hospital because of acute haematomas in the legs: the history
      revealed no cause. The pale-looking patient reported having large and foul
      smelling stools once or twice daily. There were large haematomas and swellings on
      both legs. His general and nutritional state was reduced. "Bleeding of unknown
      origin" was suspected at this time. INVESTIGATIONS: Haemoglobin concentration was
      5.6 g/dl, while iron was normal and ferritin reduced. Quick value was below 5%,
      activated partial thromboplastin time prolonged to 180 s. Vitamin A and E
      concentrations were reduced; coumarin derivatives were not demonstrated in blood.
      Abdominal ultrasonography showed clearly thickened intestinal walls. TREATMENT
      AND COURSE: Four units of erythrocyte concentrate were immediately administered,
      together with 2000 IU factors II, VII, X and anti-haemophilic factor B (PPSB),
      and 10 mg vitamin K intravenously. As intestinal malabsorption was suspected, a
      vitamin A absorption test was performed: it indicated malabsorption. Upper
      intestinal endoscopy showed coeliac disease, as did a biopsy. The patient's state
      quickly improved after he had been given vitamins A, D, E and K and put on a
      gluten-free diet. CONCLUSION: Coeliac disease can take a clinically unremarkable
      course for a long time and may finally become manifest through an isolated
      abnormality, such as bleeding.

PMID- 7588033
TI  - [Cardiovascular function during laparoscopies].

PMID- 7588031
TI  - [Aftercare in patients with colorectal carcinomas].

PMID- 7588032
TI  - [Cytokines and pancreatic diseases].

PMID- 7588034
TI  - [The dosage interval in prophylactic heparinization].

PMID- 7588035
TI  - [The probability of an embolism in the conversion of atrial fibrillation].

PMID- 7588036
TI  - [The plasma endothelin concentration during cold provocation in Raynaud's
      syndrome].

PMID- 7588037
TI  - [Endosonography in the assessment of pancreatic tumors. A comparison of the
      endosonographic findings of carcinomas and segmental inflammatory changes].
AB  - AIM OF STUDY: To examine the value of endoscopic ultrasonography in
      distinguishing malignant and benign tumours of the pancreas. PATIENTS AND
      METHODS: Endoscopic ultrasonography (EUS) was performed on 130 consecutive
      patients (35 women and 95 men; mean age 56.6 [38-71] years), 61 with carcinoma of
      the pancreas (CP), 69 with segmental inflammatory (pseudotumorous) lesions of the
      pancreas (SILP). The diagnosis was confirmed by histology in 41 cases of CP, by
      autopsy in 4, by clinical follow-up (4-56 weeks, mean of 7 months) in 16. It was
      confirmed histologically in 39 cases of SILP, by clinical follow-up in 30 (12-93
      weeks, mean of 12 months). All EUS findings were performed and recorded according
      to a standardized protocol and subsequently compared. RESULTS: There were no
      significant differences in EUS findings between CP and SILP. Statistical analysis
      between the two groups revealed any differential diagnostic relevance only with
      regard to some individual findings: coarse echo-dense deposits were seen by EUS
      in 16 of SILP cases (23%), but in only 4 of those with CP (7%), and then only in
      the face of similar changes in the rest of the organ or if there was additional
      chronic pancreatitis. Absence of demarcation from the duodenal or gastric wall
      was recorded in 18 cases of CP (30%), but in only 5 of SILP (7%). Lack of
      demarcation from the portal vein, splenic vein or coeliac artery was noted in 17
      cases of CP (28%) and 6 of SILP (9%). Extension of tumour into vessel lumens was
      seen only in CP, but even here in only 7 cases (11%). CONCLUSION: Despite the
      high resolution of EUS it does not provide reliable differentiation of benign and
      malignant lesions of the pancreas in the individual case.

PMID- 7588038
TI  - [Immune status studies after one-time alcohol consumption in healthy subjects].
AB  - AIM OF STUDY: To ascertain whether once-only intake of a large amount of alcohol
      causes measurable effects on the immune system of healthy persons. SUBJECTS AND
      METHODS: Cytokine levels, lymphocyte subpopulations and mitogen stimulation were
      measured in eleven healthy nonalcohol drinking volunteers (eight men, three
      women; mean age 30.5 [26-36] years; mean weight 71.4 kg) after a single intake of
      80 g ethanol (corresponding to 1.12 g/kg). RESULTS: There were no changes in the
      concentrations of tumour necrosis factor alpha, interleukins 1 alpha and 1 beta,
      3, 6, 10, soluble interleukin-6 receptor, interleukin-1 receptor antagonist,
      gamma-interferon and granulocyte-macrophage colony stimulating factor. A tendency
      towards an increase was measured regarding the CD-4 lymphocyte counts as well as
      the concentration of soluble interleukin-2 receptors and intercellular adhesion
      molecules (ICAM-1). Interleukins 4 and 8 were low normal. Lymphocyte activity was
      slightly reduced in the mixed lymphocyte cytotoxicity test. No clear-cut changes
      were observed in the results of the other mitogen stimulation tests. CONCLUSION:
      These data show that once-only intake of a large amount of alcohol does not
      produce measurable abnormalities in the immune system of healthy persons who
      ordinarily abstain from drinking alcohol.

PMID- 7588039
TI  - [Interstitial pneumonia and sepsis due to a Pasteurella multocida infection].
AB  - HISTORY AND CLINICAL FINDINGS: A 65-year-old diabetic (requiring insulin during
      the last year) was admitted as an emergency because of a septic temperature
      rising to 40 degrees C with rigor, tachycardia (up to 120/min) and dyspnoea. On
      examination there was local reddening and swelling of the skin over the right
      thenar eminence and along the lower arm. Two days before admission a bad scratch
      had been inflicted on his right hand by a cat. He had first noticed the reddening
      and swelling 10 hours after the incident; 1 1/2 days after the scratch and 9-10
      hours before hospitalization the first bouts of fever had occurred. EXAMINATIONS:
      The chest radiogram showed interstitial pneumonia. The clinical findings, the
      laboratory tests (white cell count 21 750/microliters, platelets
      140,000/microliters, C-reactive protein 35 mg/l and positive blood cultures
      pointed to early septicaemia. The germ was identified as Pasteurella multocida
      two days after blood had been taken for culturing. HbA1c was 11.38%. TREATMENT
      AND COURSE: From the time of hospitalization the patient had been treated with
      ceftriaxon, 2 g daily intravenously, and also with erythromycin because atypical
      pneumonia had been the suspected diagnosis at first and acute chlamydia infection
      had at first not been excluded. The patient's general condition quickly improved
      and the fever started to go down a few hours after onset of treatment. Blood
      cultures became negative after the first administration of antibiotics. He was
      discharged in a good state on optimal insulin dosage. CONCLUSION: Pasteurella
      multocida is present in a high percentage of domestic animals and can be the
      cause of systemic infections in immunocompromised patients (e. g. poorly
      controlled diabetes mellitus).

PMID- 7588040
TI  - [The internist's differential diagnosis of low back pains].

PMID- 7588041
TI  - [Conjugated estrogens].

PMID- 7588043
TI  - [The provisos for substitutes in formulaic elective performance agreements].

PMID- 7588042
TI  - [The gastrointestinal manifestations of amyloidosis].

PMID- 7588045
TI  - [New knowledge on HIV pathogenesis].

PMID- 7588044
TI  - [Insulin, glibenclamide plus acarbose in diabetes mellitus?].

PMID- 7588047
TI  - [The safe use of measles inoculation in children with an egg white allergy].

PMID- 7588046
TI  - [The effects of a self-medication program on compliance and drug knowledge in
      older patients].

PMID- 7588048
TI  - The dorsal involuting marginal zone stiffens anisotropically during its
      convergent extension in the gastrula of Xenopus laevis.
AB  - Physically, the course of morphogenesis is determined by the distribution and
      timing of force production in the embryo and by the mechanical properties of the
      tissues on which these forces act. We have miniaturized a standard materials
      testing procedure (the stress-relaxation test) to measure the viscoelastic
      properties of the dorsal involuting marginal zone, prechordal mesoderm, and
      vegetal endoderm of Xenopus laevis embryos during gastrulation. We focused on the
      involuting marginal zone, because it undergoes convergent extension (an important
      and wide-spread morphogenetic process) and drives involution, blastopore closure
      and elongation of the embryonic axis. We show that the involuting marginal zone
      stiffens during gastrulation, stiffening is a special property of this region
      rather than a general property of the whole embryo, stiffening is greater along
      the anteroposterior axis than the mediolateral axis and changes in the
      cytoskeleton or extracellular matrix are necessary for stiffening, although
      changes in cell-cell adhesions or cell-matrix adhesions are not ruled out. These
      findings provide a baseline of data on which future experiments can be designed
      and make specific, testable predictions about the roles of the cytoskeleton,
      extracellular matrix and intercellular adhesion in convergent extension, as well
      as predictions about the morphogenetic role of convergent extension in early
      development.

PMID- 7588049
TI  - Cloche, an early acting zebrafish gene, is required by both the endothelial and
      hematopoietic lineages.
AB  - Endothelial and hematopoietic cells appear synchronously on the extra-embryonic
      membranes of amniotes in structures known as blood islands. This observation has
      led to the suggestion that these two ventral lineages share a common progenitor.
      Recently, we have shown in the zebrafish, Danio rerio, that a single cell in the
      ventral marginal zone of the early blastula can give rise to both endothelial and
      blood cells as well as to other mesodermal cells (Stainier, D. Y. R., Lee, R. K.
      and Fishman, M. C. (1993). Development 119, 31-40; Lee, R. K. K., Stainier, D. Y.
      R., Weinstein, B. M. and Fishman, M. C. (1994). Development 120, 3361-3366). Here
      we describe a zebrafish mutation, cloche, that affects both the endothelial and
      hematopoietic lineages at a very early stage. The endocardium, the endothelial
      lining of the heart, is missing in mutant embryos. This deletion is selective as
      evidenced by the presence of other endothelial cells, for example those lining
      the main vessels of the trunk. Early cardiac morphogenesis proceeds normally even
      in the absence of the endocardium. The myocardial cells form a tube that is
      demarcated into chambers, beats rhythmically, but exhibits a reduced
      contractility. This functional deficit is likely due to the absence of the
      endocardial cells, although it may be a direct effect of the mutation on the
      myocardial cells. Cell transplantation studies reveal that the endothelial
      defect, i.e. the endocardial deletion, is a cell-autonomous lesion, consistent
      with the possibility that cloche is part of a signal transduction pathway. In
      addition, the number of blood cells is greatly reduced in cloche mutants and the
      hematopoietic tissues show no expression of GATA-1 or GATA-2, two key
      hematopoietic transcription factors that are first expressed during early
      embryogenesis. These results show that cloche is involved in the genesis and
      early diversification of the endothelial and blood lineages, possibly by
      affecting a common progenitor cell population.

PMID- 7588050
TI  - Formin isoforms are differentially expressed in the mouse embryo and are required
      for normal expression of fgf-4 and shh in the limb bud.
AB  - Mice homozygous for the recessive limb deformity (ld) mutation display both limb
      and renal defects. The limb defects, oligodactyly and syndactyly, have been
      traced to improper differentiation of the apical ectodermal ridge (AER) and
      shortening of the anteroposterior limb axis. The renal defects, usually aplasia,
      are thought to result from failure of ureteric bud outgrowth. Since the ld locus
      gives rise to multiple RNA isoforms encoding several different proteins (termed
      formins), we wished to understand their role in the formation of these organs.
      Therefore, we first examined the embryonic expression patterns of the four major
      ld mRNA isoforms. Isoforms I, II and III (all containing a basic amino terminus)
      are expressed in dorsal root ganglia, cranial ganglia and the developing kidney
      including the ureteric bud. Isoform IV (containing an acidic amino terminus) is
      expressed in the notochord, the somites, the apical ectodermal ridge (AER) of the
      limb bud and the developing kidney including the ureteric bud. Using a lacZ
      reporter assay in transgenic mice, we show that this differential expression of
      isoform IV results from distinct regulatory sequences upstream of its first exon.
      These expression patterns suggest that all four isoforms may be involved in
      ureteric bud outgrowth, while isoform IV may be involved in AER differentiation.
      To define further the developmental consequences of the ld limb defect, we
      analyzed the expression of a number of genes thought to play a role in limb
      development. Most significantly, we find that although the AERs of ld limb buds
      express several AER markers, they do not express detectable levels of fibroblast
      growth factor 4 (fgf-4), which has been proposed to be the AER signal to the
      mesoderm. Thus we conclude that one or more formins are necessary to initiate
      and/or maintain fgf-4 production in the distal limb. Since ld limbs form distal
      structures such as digits, we further conclude that while fgf-4 is capable of
      supporting distal limb outgrowth in manipulated limbs, it is not essential for
      distal outgrowth in normal limb development. In addition, ld limbs show a severe
      decrease in the expression of several mesodermal markers, including sonic
      hedgehog (shh), a marker for the polarizing region and Hoxd-12, a marker for
      posterior mesoderm. We propose that incomplete differentiation of the AER in ld
      limb buds leads to reduction of polarizing activity and defects along the
      anteroposterior axis.

PMID- 7588051
TI  - Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during
      induction and regionalization of the chick hindgut.
AB  - Reciprocal inductive signals between the endoderm and mesoderm are critical to
      vertebrate gut development. Sonic hedgehog encodes a secreted protein known to
      act as an inductive signal in several regions of the developing embryo. In this
      report, we provide evidence to support the role of Sonic hedgehog and its target
      genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the
      chick hindgut. Sonic is expressed in the definitive endoderm at the earliest
      stage of chick gut formation. Immediately subjacent to Sonic expression in the
      caudal endoderm is undifferentiated mesoderm, later to become the visceral
      mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF
      beta relative implicated in proper growth of visceral mesoderm) and members of
      the Abd-B class of Hox genes (known regulators of pattern in many aspects of
      development). Using virally mediated misexpression, we show that Sonic hedgehog
      is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes
      within the mesoderm. Sonic therefore appears to act as a signal in an epithelial
      mesenchymal interaction in the earliest stages of chick hindgut formation. Gut
      pattern is evidenced later in gut morphogenesis with the presence of anatomic
      boundaries reflecting phenotypically and physiologically distinct regions. The
      expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut
      and these Hox expression domains reflect gut morphologic boundaries. This finding
      strongly supports a role for these genes in determining the adult gut phenotype.
      Our results provide the basis for a model to describe molecular controls of early
      vertebrate hindgut development and patterning. Expression of homologous genes in
      Drosophila suggest that aspects of gut morphogenesis may be regulated by similar
      inductive networks in the two organisms.

PMID- 7588052
TI  - Modifications of cell fate specification in equal-cleaving nemertean embryos:
      alternate patterns of spiralian development.
AB  - The nemerteans belong to a phylum of coelomate worms that display a highly
      conserved pattern of cell divisions referred to as spiral cleavage. It has
      recently been shown that the fates of the four embryonic cell quadrants in two
      species of nemerteans are not homologous to those in other spiralian embryos,
      such as the annelids and molluscs (Henry, J. Q. and Martindale, M. Q. (1994a)
      Develop. Genetics 15, 64-78). Equal-cleaving molluscs utilize inductive
      interactions to establish quadrant-specific cell fates and embryonic symmetry
      properties following fifth cleavage. In order to elucidate the manner in which
      cell fates are established in nemertean embryos, we have conducted cell isolation
      and deletion experiments to examine the developmental potential of the early
      cleavage blastomeres of two equal-cleaving nemerteans, Nemertopsis bivittata and
      Cerebratulus lacteus. These two species display different modes of development:
      N. bivittata develops directly via a non-feeding larvae, while C. lacteus
      develops to form a feeding pilidium larva which undergoes a radical metamorphosis
      to give rise to the juvenile worm. By examining the development of certain
      structures and cell types characteristic of quadrant-specific fates for each of
      these species, we have shown that isolated blastomeres of the indirect-developing
      nemertean, C. lacteus, are capable of generating cell fates that are not a
      consequence of that cell's normal developmental program. For instance, dorsal
      blastomeres can form muscle fibers when cultured in isolation. In contrast,
      isolated blastomeres of the direct-developing species, N. bivittata do not
      regulate their development to the same extent. Some cell fates are specified in a
      precocious manner in this species, such as those that give rise to the eyes.
      Thus, these findings indicate that equal-cleaving spiralian embryos can utilize
      different mechanisms of cell fate and axis specification. The implications of
      these patterns of nemertean development are discussed in relation to experimental
      work in other spiralian embryos, and a model is presented that accounts for
      possible evolutionary changes in cell lineage and the process of cell fate
      specification amongst these protostome phyla.

PMID- 7588053
TI  - The prospero transcription factor is asymmetrically localized to the cell cortex
      during neuroblast mitosis in Drosophila.
AB  - Both intrinsic and extrinsic factors are known to regulate sibling cell fate.
      Here we describe a novel mechanism for the asymmetric localization of a
      transcription factor to one daughter cell at mitosis. The Drosophila CNS develops
      from asymmetrically dividing neuroblasts, which give rise to a large neuroblast
      and a smaller ganglion mother cell (GMC). The prospero gene encodes a
      transcription factor necessary for proper GMC gene expression. We show that the
      prospero protein is synthesized in the neuroblast where it is localized to the F
      actin cell cortex. At mitosis, prospero is asymmetrically localized to the
      budding GMC and excluded from the neuroblast. After cytokinesis, prospero is
      translocated from the GMC cortex into the nucleus. Asymmetric cortical
      localization of prospero in neuroblasts requires entry into mitosis; it does not
      depend on numb function. prospero is also observed in cortical crescents in
      dividing precursors of the peripheral nervous system and adult midgut. The
      asymmetric cortical localization of prospero at mitosis is a mechanism for
      rapidly establishing distinct sibling cell fates in the CNS and possibly other
      tissues.

PMID- 7588056
TI  - Micromeres are required for normal vegetal plate specification in sea urchin
      embryos.
AB  - Vegetal plate specification was assessed in S. purpuratus embryos after micromere
      deletions at the 4th, 5th and 6th cleavages, by assaying expression of the early
      vegetal plate marker Endo 16, using whole-mount in situ hybridization. After 4th
      cleavage micromere deletions, the embryos typically displayed weak Endo16
      expression in relatively few cells of the lineages that normally constitute the
      vegetal plate, while after 5th and 6th cleavage micromere deletions the embryos
      exhibited strong Endo16 expression in larger fractions of cells belonging to
      those lineages. When all four micromeres were deleted, the embryos were severely
      delayed in initiating gastrulation and sometimes failed to complete gastrulation.
      However, if only one micromere was allowed to remain in situ throughout
      development, the embryos exhibited strong Endo16 expression and gastrulation
      occurred normally, on schedule with controls. Additional measurements showed that
      these microsurgical manipulations do not alter cleavage rates or generally
      disrupt embryo organization. These results constitute direct evidence that the
      micromeres provide signals required by the macromere lineages for initiation of
      vegetal plate specification. The specification of the vegetal plate is completed
      in a normal manner only if micromere signaling is allowed to continue at least to
      the 6th cleavage stage.

PMID- 7588054
TI  - Expression of the labial group Hox gene HrHox-1 and its alteration induced by
      retinoic acid in development of the ascidian Halocynthia roretzi.
AB  - Ascidian embryogenesis shares several developmental features with vertebrates.
      Thus, it is presumed that some molecular mechanisms that are critical for
      vertebrate development may also act in the early development of ascidians. Here,
      we investigated expression of the ascidian labial group Hox gene HrHox-1 in the
      development of Halocynthia roretzi. HrHox-1 showed a spatially restricted
      expression pattern along the anterior-posterior axis, which is remarkably similar
      to that of the vertebrate gene, Hoxb-1. The expression of HrHox-1, however, was
      exclusively in tissues of ectoderm origin unlike its vertebrate counterpart.
      Exposure of the embryos to 10(-6) M all-trans retinoic acid induced a larval
      phenotype with elimination of the anteriormost structures, the papillae. In this
      phenotype, the level of HrHox-1 expression was enhanced and ectopic expression
      was observed at the anterior terminal epidermis where the papillae are otherwise
      formed. These observations suggest that there are some conserved mechanisms in
      the spatial regulation of expression of labial group genes in embryogenesis of
      ascidians and vertebrates.

PMID- 7588057
TI  - Expression and transgenic studies of the mouse agouti gene provide insight into
      the mechanisms by which mammalian coat color patterns are generated.
AB  - Expression of the agouti gene from two different promoters, one active at the
      midpoint of the hair cycle and the other specific for the ventrum, is responsible
      for generating a range of mammalian pigmentation patterns. We demonstrate that in
      postnatal mice transcripts from both promoters are confined to the dermal papilla
      of hair follicles, as predicted by classical transplantation experiments.
      Transcripts from the hair cycle promoter are detected in the embryonic whisker
      plate but not in other regions of the body before birth, whereas ventral-specific
      transcripts are detected in the ventral trunk of the embryo as well as ventral
      whisker plate. To investigate further the embryonic origins of adult pigmentation
      patterns, we carried out a detailed analysis of agouti expression in the embryo.
      The ventral-specific agouti isoform is first expressed at E10.5 in neural crest
      derived ventral cells of the second branchial arch, in anterior regions of the
      forelimb buds and in a narrow stripe of ventral mesenchyme. By E14.5 a continuous
      layer of expression is observed in the upper cells of the dermis, including cells
      of the developing dermal papillae, and covering the entire ventral surface of the
      head and trunk and dorsal surfaces of the distal forelimb and hindlimb. This
      expression pattern reflects the domain of yellow coloration evident in adult
      animals and suggests that the agouti gene is regulated in part by factors
      responsible for establishing differences between the dorsal and ventral surfaces
      of the body during embryogenesis. To test the hypothesis that agouti is a
      paracrine signaling molecule that can influence pigment production by hair
      follicle melanocytes when expressed by either dermis or epidermis, as suggested
      by recombination and transplantation experiments, we created transgenic animals
      in which agouti is expressed in basal cells of the epidermis. These animals
      display stripes of yellow hairs corresponding to regions of epidermal agouti
      expression, confirming that agouti signals melanocytes to synthesize yellow
      pigment and providing direct evidence that it functions in a paracrine manner
      with a restricted radius of action.

PMID- 7588058
TI  - The role of the cell cycle and cytokinesis in regulating neuroblast sublineage
      gene expression in the Drosophila CNS.
AB  - The precise temporal control of gene expression is critical for specifying
      neuronal identity in the Drosophila central nervous system (CNS). A particularly
      interesting class of genes are those expressed at stereotyped times during the
      cell lineage of identified neural precursors (neuroblasts): these are termed
      'sublineage' genes. Although sublineage gene function is vital for CNS
      development, the temporal regulation of this class of genes has not been studied.
      Here we show that four genes (ming, even-skipped, unplugged and achaete) are
      expressed in specific neuroblast sublineages. We show that these neuroblasts can
      be identified in embryos lacking both neuroblast cytokinesis and cell cycle
      progression (string mutants) and in embryos lacking only neuroblast cytokinesis
      (pebble mutants). We find that the unplugged and achaete genes are expressed
      normally in string and pebble mutant embryos, indicating that temporal control is
      independent of neuroblast cytokinesis or counting cell cycles. In contrast,
      neuroblasts require cytokinesis to activate sublineage ming expression, while a
      single, identified neuroblast requires cell cycle progression to activate even
      skipped expression. These results suggest that neuroblasts have an intrinsic gene
      regulatory hierarchy controlling unplugged and achaete expression, but that cell
      cycle- or cytokinesis-dependent mechanisms are required for ming and eve CNS
      expression.

PMID- 7588055
TI  - The metanephric blastema differentiates into collecting system and nephron
      epithelia in vitro.
AB  - The kidney forms from two tissue populations derived from intermediate mesoderm,
      the ureteric bud and metanephric mesenchyme. It is currently accepted that
      metanephric mesenchyme is committed to differentiating into nephrons while the
      ureteric bud is restricted to forming the renal collecting system. To test this
      hypothesis, we transferred lacZ into pure metanephric mesenchyme isolated from
      gestation day 13 rat embryos. The fate of tagged mesenchymal cells and their
      progeny was characterized after co-culture with isolated ureteric buds. When
      induced to differentiate by the native inducer of kidney morphogenesis, lineage
      tagged mesenchymal cells exhibit the potential to differentiate into collecting
      system epithelia, in addition to nephrons. The fate of cells deriving from
      isolated ureteric buds was also examined and results of these lacZ gene transfer
      experiments indicate that the majority of ureteric bud cells differentiate into
      the renal collecting system. These cell fate studies combined with in situ
      morphological observations raise the possibility that collecting system
      morphogenesis in vivo occurs by growth of the ureteric bud and recruitment of
      mesenchymal cells from the metanephric blastema. Thus, metanephric mesenchyme may
      be a pluripotent renal stem population.

PMID- 7588059
TI  - The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding
      protein whose expression is sex specifically regulated by Sex-lethal.
AB  - In Drosophila dosage compensation increases the rate of transcription of the
      male's X chromosome and depends on four autosomal male-specific lethal genes. We
      have cloned the msl-2 gene and shown that MSL-2 protein is co-localized with the
      other three MSL proteins at hundreds of sites along the male polytene X
      chromosome and that this binding requires the other three MSL proteins. msl-2
      encodes a protein with a putative DNA-binding domain: the RING finger. MSL-2
      protein is not produced in females and sequences in both the 5' and 3' UTRs are
      important for this sex-specific regulation. Furthermore, msl-2 pre-mRNA is
      alternatively spliced in a Sex-lethal-dependent fashion in its 5' UTR.

PMID- 7588060
TI  - Repetitive sperm-induced Ca2+ transients in mouse oocytes are cell cycle
      dependent.
AB  - Mature mouse oocytes are arrested at metaphase of the second meiotic division.
      Completion of meiosis and a block to polyspermy is caused by a series of
      repetitive Ca2+ transients triggered by the sperm at fertilization. These Ca2+
      transients have been widely reported to last for a number of hours but when, or
      why, they cease is not known. Here we show that Ca2+ transients cease during
      entry into interphase, at the time when pronuclei are forming. In fertilized
      oocytes arrested at metaphase using colcemid, Ca2+ transients continued for as
      long as measurements were made, up to 18 hours after fertilization. Therefore
      sperm is able to induce Ca2+ transients during metaphase but not during
      interphase. In addition metaphase II oocytes, but not pronuclear stage 1-cell
      embryos showed highly repetitive Ca2+ oscillations in response to microinjection
      of inositol trisphosphate. This was explored further by treating in vitro
      maturing oocytes at metaphase I for 4-5 hours with cycloheximide, which induced
      nuclear progression to interphase (nucleus formation) and subsequent re-entry to
      metaphase (nuclear envelope breakdown). Fertilization of cycloheximide-treated
      oocytes revealed that continuous Ca2+ oscillations in response to sperm were
      observed after nuclear envelope breakdown but not during interphase. However
      interphase oocytes were able to generate Ca2+ transients in response to
      thimerosal. This data suggests that the ability of the sperm to trigger
      repetitive Ca2+ transients in oocytes is modulated in a cell cycle-dependent
      manner.

PMID- 7588062
TI  - Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective
      anterior neuroectoderm specification during gastrulation.
AB  - We have replaced part of the mouse homeogene Otx2 coding region with the E. coli
      lacZ coding sequence, thus creating a null allele of Otx2. By 9.5 dpc, homozygous
      mutant embryos are characterized by the absence of forebrain and midbrain
      regions. From the early to midstreak stages, endomesodermal cells expressing lacZ
      fail to be properly localized anteriorly. In the ectodermal layer, lacZ
      transcription is progressively extinguished, being barely detectable by the late
      streak stage. These data suggest that Otx2 expression in endomesoderm and
      ectoderm is required for anterior neuroectoderm specification. In gastrulating
      heterozygous embryos, a post-transcriptional repression acts on lacZ transcripts
      in the ectoderm, but not in the external layer, suggesting that different post
      transcriptional mechanisms control Otx2 expression in both layers.

PMID- 7588061
TI  - Midline signalling is required for Pax gene regulation and patterning of the
      eyes.
AB  - Pax6 and Pax2 are members of the Pax family of transcription factors that are
      both expressed in the developing visual system of zebrafish embryos. Pax6 protein
      is present in all cells that form the neural retina and pigment epithelium,
      whereas Pax2 is located primarily in cells that will give rise to the optic
      stalk. In this study, we have addressed the role of midline signalling in the
      regulation of Pax2 and Pax6 distributions and in the subsequent morphogenesis of
      the eyes. Midline signalling is severely perturbed in cyclops mutant embryos
      resulting in an absence of ventral midline CNS tissue and fusion of the eyes.
      Mutant embryos ectopically express Pax6 in a bridge of tissue around the anterior
      pole of the neural keel in the position normally occupied by cells that form the
      optic stalks. In contrast, Pax2 protein is almost completely absent from this
      region in mutant embryos. Concommitant with the changes in Pax protein
      distribution, cells in the position of the optic stalks differentiate as retina.
      These results suggest that a signal emanating from the midline, which is absent
      in cyclops mutant embryos, may be required to promote Pax2 and inhibit Pax6
      expression in cells destined to form the optic stalks. Sonic hedgehog (Shh also
      known as Vhh-1 and Hhg-1) is a midline signalling molecule that is absent from
      the neuroepithelium of cyclops mutant embryos at early developmental stages. To
      test the possibility that Shh might be able to regulate the spatial expression of
      Pax6 and Pax2 in the optic primordia, it was overexpressed in the developing CNS.
      The number of cells containing Pax2 was increased following shh overexpression
      and embryos developed hypertrophied optic stalk-like structures. Complimentary to
      the changes in Pax2 distribution, there were fewer Pax6-containing cells and
      pigment epithelium and neural retina were reduced. Our results suggest that Shh
      or a closely related signalling molecule emanating from midline tissue in the
      ventral forebrain either directly or indirectly induces the expression of Pax2
      and inhibits the expression of Pax6 and thus may regulate the partitioning of the
      optic primordia into optic stalks and retinal tissue.

PMID- 7588063
TI  - Disruption of the mouse RBP-J kappa gene results in early embryonic death.
AB  - The RBP-J kappa protein is a transcription factor that recognizes the sequence
      C(T)GTGGGGA. The RBP-J kappa gene is highly conserved in a wide variety of
      species and the Drosophila homologue has been shown to be identical to Suppressor
      of Hairless [Su(H)] which plays important roles in the development of the
      peripheral nervous system. To explore the function of the RBP-J kappa gene in
      mouse embryogenesis, a mutation was introduced into the functional RBP-J kappa
      gene in embryonic stem (ES) cells by homologous recombination. Null mutant ES
      cells survived but null mutant mice showed embryonic lethality before 10.5 days
      of gestation. The mutant mice showed severe growth retardation as early as 8.5
      days of gestation. Developmental abnormalities, including incomplete turning of
      the body axis, microencephaly, abnormal placental development, anterior neuropore
      opening and defective somitogenesis, were observed in the mutant mice at 9.5 days
      of gestation. RBP-J kappa mutant embryos expressed a posterior mesodermal marker
      FGFR1. Their irregularly shaped somites expressed a somite marker gene Mox 1 but
      failed to express myogenin. The RBP-J kappa gene was revealed to be essential for
      postimplantation development of mice.

PMID- 7588064
TI  - Formation of lateral root meristems is a two-stage process.
AB  - In both radish and Arabidopsis, lateral root initiation involves a series of
      rapid divisions in pericycle cells located on the xylem radius of the root. In
      Arabidopsis, the number of pericycle cells that divide to form a primordium was
      estimated to be about 11. To determine the stage at which primordia are able to
      function as root meristems, primordia of different stages were excised and
      cultured without added hormones. Under these conditions, primordia that consist
      of 2 cell layers fail to develop while primordia that consist of at least 3-5
      cell layers develop as lateral roots. We hypothesize that meristem formation is a
      two-step process involving an initial period during which a population of rapidly
      dividing, approximately isodiametric cells that constitutes the primordium is
      formed, and a subsequent stage during which meristem organization takes place
      within the primordium.

PMID- 7588065
TI  - Induction of notochord cell intercalation behavior and differentiation by
      progressive signals in the gastrula of Xenopus laevis.
AB  - We show that notochord-inducing signals are present during Xenopus laevis
      gastrulation and that they are important for both inducing and organizing cell
      behavior and differentiation in the notochord. Previous work showed that
      convergent extension of prospective notochordal and somitic mesoderm occurs by
      mediolateral cell intercalation to produce a longer, narrower tissue.
      Mediolateral cell intercalation is driven by bipolar, mediolaterally directed
      protrusive activity that elongates cells and then pulls them between one another
      along the mediolateral axis. This cell behavior, and subsequent notochordal cell
      differentiation, begins anteriorly and spreads posteriorly along the notochordal
      somitic boundary, and from this lateral boundary progresses medially towards the
      center of the notochord field. To examine whether these progressions of cell
      behaviors and differentiation are induced and organized during gastrulation, we
      grafted labeled cells from the prospective notochordal, somitic and epidermal
      regions of the gastrula into the notochordal region and monitored their behavior
      by low light, fluorescence videomicroscopy. Prospective notochordal, epidermal
      and somitic cells expressed mediolateral cell intercalation behavior in an
      anterior-to-posterior and lateral-to-medial order established by the host
      notochord. Behavioral changes were induced first and most dramatically among
      cells grafted next to the notochordal-somitic boundary, particularly those in
      direct contact with the boundary, suggesting that the boundary may provide
      signals that both induce and organize notochordal cell behaviors. By physically
      impeding normal convergent extension movements, notochordal cell behaviors and
      differentiation were restricted to the anteriormost notochordal region and to the
      lateral notochordal-somitic boundary. These results show that mediolateral cell
      intercalation behavior and notochordal differentiation can be induced in the
      gastrula stage, among cells not normally expressing these characteristics, and
      that these characteristics are induced progressively, most likely by signals
      emanating from the notochordal-somitic boundary. In addition, they show that
      morphogenetic movements during gastrulation are necessary for complete notochord
      formation and that the prospective notochord region is not determined by the
      onset of gastrulation.

PMID- 7588066
TI  - DPY-30, a nuclear protein essential early in embryogenesis for Caenorhabditis
      elegans dosage compensation.
AB  - DPY-30 is an essential component of the C. elegans dosage compensation machinery
      that reduces X chromosome transcript levels in hermaphrodites (XX). DPY-30 is
      required for the sex-specific association of DPY-27 (a chromosome condensation
      protein homolog) with the hermaphrodite X chromosomes. Loss of dpy-30 activity
      results in XX-specific lethality. We demonstrate that dpy-30 encodes a novel
      nuclear protein of 123 amino acids that is present in both hermaphrodites and
      males (XO) throughout development. DPY-30 itself is not associated with the X
      chromosomes, nor is its pattern of expression perturbed by mutations in the gene
      hierarchy that controls dosage compensation. Therefore, DPY-30 is a ubiquitous
      factor that is likely to promote the hermaphrodite-specific association of DPY-27
      with X by affecting the activity of a sex-specific dosage compensation gene. In
      XO animals, DPY-30 is required for developmental processes other than dosage
      compensation: coordinated movement, normal body size, correct tail morphology and
      mating behavior. We demonstrate that rescue of both the XX-specific lethality and
      the XO-specific morphological defects caused by dpy-30 mutations can be achieved
      by inducing dpy-30 transcripts either in the mother or in the embryo through the
      end of gastrulation. dpy-30 appears to be cotranscribed in an operon with a novel
      RNA-binding protein.

PMID- 7588067
TI  - A new approach to the study of haematopoietic development in the yolk sac and
      embryoid bodies.
AB  - To understand the mechanisms that control the differentiation of uncommitted
      mesoderm precursors into haematopoietic stem cells (HSCs) and the activation of
      haematopoiesis, we conducted a study to identify genes expressed at the earliest
      stages of both in vivo and in vitro haematopoietic development. Our strategy was
      to utilize Differential Display by means of the Polymerase Chain Reaction (DD
      PCR) to compare patterns of gene expression between mRNA populations representing
      different levels of haematopoietic activity obtained from the mouse embryo,
      embryoid bodies (EBs) and mouse cell lines. We report the molecular cloning of
      two groups of genes expressed in the yolk sac: a group of genes expressed in the
      day-8.5 yolk sac at higher levels than in the day-8.5 embryo proper and up
      regulated during EB development, and another group of day-8.5 yolk sac genes not
      expressed in the day-8.5 embryo proper or in EBs. Specifically, we describe the
      molecular cloning of the first nucleobase permease gene to be found in
      vertebrates, yolk sac permease-like molecule 1 (Ysp11). The Ysp11 gene has the
      unique property of encoding both intracellular, transmembrane and extracellular
      protein forms, revealing novel aspects of nucleotide metabolism that may be
      relevant during mammalian development.

PMID- 7588068
TI  - Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the
      myotome.
AB  - MRF4 (herculin/Myf-6) is one of the four member MyoD family of transcription
      factors identified by their ability to enforce skeletal muscle differentiation
      upon a wide variety of nonmuscle cell types. In this study the mouse germline
      MRF4 gene was disrupted by targeted recombination. Animals homozygous for the
      MRF4bh1 allele, a deletion of the functionally essential bHLH domain, displayed
      defective axial myogenesis and rib pattern formation, and they died at birth.
      Differences in somitogenesis between homozygous MRF4bh1 embryos and their wild
      type littermates provided evidence for three distinct myogenic regulatory
      programs (My1-My3) in the somite, which correlate temporally and spatially with
      three waves of cellular recruitment to the expanding myotome. The first program
      (My1), marked initially by Myf-5 expression and followed by myogenin, began on
      schedule in the MRF4bh1/bh1 embryos at day 8 post coitum (E8). A second program
      (My2) was highly deficient in homozygous mutant MRF4 embryos, and normal
      expansion of the myotome failed. Moreover, expression of downstream muscle
      specific genes, including FGF-6, which is a candidate regulator of inductive
      interactions, did not occur normally. The onset of MyoD expression around E10.5
      in wild-type embryos marks a third myotomal program (My3), the execution of which
      was somewhat delayed in MRF4 mutant embryos but ultimately led to extensive
      myogenesis in the trunk. By E15 it appeared to have largely compensated for the
      defective My2 program in MRF4 mutants. Homozygous MRF4bh1 animals also showed
      improper rib pattern formation perhaps due to the absence of signals from cells
      expressing the My2 program. Finally, a later and relatively mild phenotype was
      detected in intercostal muscles of newborn animals.

PMID- 7588069
TI  - Creating a Drosophila wing de novo, the role of engrailed, and the compartment
      border hypothesis.
AB  - Anterior/posterior compartment borders bisect every Drosophila imaginal disc, and
      the engrailed gene is essential for their function. We analyzed the role of the
      engrailed and invected genes in wing discs by eliminating or increasing their
      activity. Removing engrailed/invected from posterior wing cells created two new
      compartments: an anterior compartment consisting of mutant cells and a posterior
      compartment that grew from neighboring cells. In some cases, these compartments
      formed a complete new wing. Increasing engrailed activity also affected
      patterning. These findings demonstrate that engrailed both directs the posterior
      compartment pathway and creates the compartment border. These findings also
      establish the compartment border as the pre-eminent organizational feature of
      disc growth and patterning.

PMID- 7588070
TI  - Ectopic cyclin E expression induces premature entry into S phase and disrupts
      pattern formation in the Drosophila eye imaginal disc.
AB  - During animal development, cell proliferation is controlled in many cases by
      regulation of the G1 to S phase transition. Studies of mammalian tissue culture
      cells have shown that the G1-specific cyclin, cyclin E, can be rate limiting for
      progression from G1 to S phase. During Drosophila development, down-regulation of
      cyclin E is required for G1 arrest in terminally differentiating embryonic
      epidermal cells. Whether cyclin E expression limits progression into S phase in
      proliferating, as opposed to differentiating, cells during development has not
      been investigated. Here we show that Drosophila cyclin E (DmcycE) protein is
      absent in G1 phase cells but appears at the onset of S phase in proliferating
      cells of the larval optic lobe and eye imaginal disc. We have examined cells in
      the eye imaginal epithelium, where a clearly defined developmentally regulated G1
      to S phase transition occurs. Ectopic expression of DmcycE induces premature
      entry of most of these G1 cells into S phase. Thus in these cells, control of
      DmcycE expression is required for regulated entry into S phase. Significantly, a
      band of eye imaginal disc cells in G1 phase was not induced to enter S phase by
      ectopic expression of DmcycE. This provides evidence for additional regulatory
      mechanisms that operate during G1 phase to limit cell proliferation during
      development. These results demonstrate that the role of cyclin E in regulating
      progression into S phase in mammalian tissue culture cells applies to some, but
      not all, cells during Drosophila development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588072
TI  - A Drosophila protein related to the human zinc finger transcription factor
      PRDII/MBPI/HIV-EP1 is required for dpp signaling.
AB  - Little is known about the signal transduction pathways by which cells respond to
      mammalian TGF-beta s or to decapentaplegic (dpp), a Drosophila TGF-beta-related
      factor. Here we describe the genetic and molecular characterization of Drosophila
      schnurri (shn), a putative transcription factor implicated in dpp signaling. The
      shn protein has eight zinc fingers and is related to a human transcription
      factor, PRDII/MBPI/HIV-EP1, that binds to nuclear factor-kappa B-binding sites
      and activates transcription from the HIV long terminal repeat (LTR). shn mRNA is
      expressed in a dynamic pattern in the embryo that includes most of the known
      target tissues of dpp, including the dorsal blastoderm, the mesodermal germlayer
      and parasegments 4 and 7 of the midgut. Mutations in shn affect several
      developmental processes regulated by dpp including induction of visceral mesoderm
      cell fate, dorsal/ventral patterning of the lateral ectoderm and wing vein
      formation. Absence of shn function blocks the expanded expression of the
      homeodomain protein bagpipe in the embryonic mesoderm caused by ectopic dpp
      expression, illustrating a requirement for shn function downstream of dpp action.
      We conclude that shn function is critical for cells to respond properly to dpp
      and propose that shn protein is the first identified downstream component of the
      signal transduction pathway used by dpp and its receptors.

PMID- 7588073
TI  - Ventral veinless, the gene encoding the Cf1a transcription factor, links
      positional information and cell differentiation during embryonic and imaginal
      development in Drosophila melanogaster.
AB  - The ventral veinless gene (vvl) encodes the previously identified Cf1a protein, a
      transcription factor containing a POU-domain. During embryonic development vvl
      function is required for the formation of the tracheal tree and in the patterning
      of the ventral ectoderm. During imaginal development vvl is required for cell
      proliferation and the differentiation of the wing veins. vvl expression is
      restricted to the regions where its function is required, and is dependent on the
      coordinate activities of signalling molecules such as decapentaplegic, wingless
      and hedgehog. vvl interacts with other genes involved in vein differentiation,
      including veinlet, thick veins, torpedo, decapentaplegic and Notch suggesting
      that vvl function may affect several cell-to-cell communication pathways. We
      propose that the gene vvl integrates information from different signalling
      molecules and regulates the expression of specific cell differentiation genes
      during tracheal development and vein differentiation.

PMID- 7588074
TI  - Establishment of left-right asymmetry in the Caenorhabditis elegans embryo: a
      multistep process involving a series of inductive events.
AB  - Bilateral pairs of blastomeres derived from the founder cell AB, the anterior
      blastomere of the 2-cell stage, in the Caenorhabditis elegans embryo are
      initially equivalent in their developmental potential. Recently, we showed that
      an induction at the 12-cell stage by a blastomere called MS is necessary to
      establish the differences between left and right pairs of blastomeres in the
      anterior part of the embryo. Further analysis of the process of creating left
      right asymmetry reveals that the induction at the 12-cell stage is only the first
      of a series of inductions establishing the left-right asymmetry of the embryo. We
      describe here two further inductions that create additional asymmetries in the
      posterior part of the embryo. One induction occurs at the 24-cell stage among AB
      descendants themselves. This induction is restricted to the left side of the
      embryo as a consequence of the fate changes induced by MS at the 12-cell stage.
      The second induction requires again blastomeres of the MS lineage and also occurs
      around the 24-cell stage. Together these inductions establish the fate
      differences observed in the development of left-right pairs of blastomeres in the
      embryo.

PMID- 7588071
TI  - Developing inner ear sensory neurons require TrkB and TrkC receptors for
      innervation of their peripheral targets.
AB  - The trkB and trkC genes are expressed during the formation of the vestibular and
      auditory system. To elucidate the function of trkB and trkC during this process,
      we have analysed mice carrying a germline mutation in the tyrosine kinase
      catalytic domain of these genes. Neuroanatomical analysis of homozygous mutant
      mice revealed neuronal deficiencies in the vestibular and cochlear ganglia. In
      trkB (-/-) animals vestibular neurons and a subset of cochlear neurons
      responsible for the innervation of outer hair cells were drastically reduced. The
      peripheral targets of the respective neurons showed severe innervation defects. A
      comparative analysis of ganglia from trkC (-/-) mutants revealed a moderate
      reduction of vestibular neurons and a specific loss of cochlear neurons
      innervating inner hair cells. No nerve fibres were detected in the sensory
      epithelium containing inner hair cells. A developmental study of trkB (-/-) and
      trkC (-/-) mice showed that some vestibular and cochlear fibres initially reached
      their peripheral targets but failed to maintain innervation and degenerated. TrkB
      and TrkC receptors are therefore required for the survival of specific neuronal
      populations and the maintenance of target innervation in the peripheral sensory
      system of the inner ear.

PMID- 7588075
TI  - Progressive maturation of chromatin structure regulates HSP70.1 gene expression
      in the preimplantation mouse embryo.
AB  - In the widely studied model organisms, Drosophila and Xenopus, early
      embryogenesis involves an extended series of nuclear divisions prior to
      activation of the zygotic genome. The mammalian embryo differs in that the early
      cleavage phase is already characterized by regulated cell cycles with specific
      zygotic gene expression. In the mouse, where major activation of the zygotic
      genome occurs at the 2-cell stage, the HSP70.1 gene is among the earliest genes
      to be expressed. We investigated the developmentally regulated expression of this
      gene during the preimplantation period, using a luciferase transgene, with or
      without flanking scaffold attachment regions (SARs). Cleavage stage-specific
      modifications in expression profiles were examined in terms of histone H4
      acetylation status, topoisomerase II activity, and the localisation of HMG-I/Y, a
      nuclear protein with known affinity for the AT-tracts of SARs. We demonstrate
      that HSP70.1-associated transcription factors are not limiting, and that instead,
      there is a progressive maturation of chromatin structure that is directly
      involved in HSP70.1 regulation during early mouse development.

PMID- 7588078
TI  - The sperm entry point defines the orientation of the calcium-induced contraction
      wave that directs the first phase of cytoplasmic reorganization in the ascidian
      egg.
AB  - Ascidians eggs are spawned with their cytoskeleton and organelles organized along
      a preexisting animal-vegetal axis. Fertilization triggers a spectacular
      microfilament-dependant cortical contraction that causes the relocalization of
      preexisting cytoplasmic domains and the creation of new domains in the lower part
      of the vegetal hemisphere. We have investigated the relationship between
      fertilization, the cortical contraction and the localization of cytoplasmic
      domains in eggs of the ascidian Phallusia mammillata. We have also examined the
      link between this first phase of ooplasmic segregation and the site of
      gastrulation. The cortical contraction was found to be initiated on the side of
      the egg where intracellular calcium is first released either by the entering
      sperm or by photolysis of caged InsP3. The cortical contraction carries the sperm
      nucleus towards the vegetal hemisphere along with a subcortical mitochondria-rich
      domain (the myoplasm). If the sperm enters close to the animal or vegetal poles
      the cortical contraction is symmetrical, travelling along the animal-vegetal
      axis. If the sperm enters closer to the equator, the contraction is asymmetrical
      and its direction does not coincide with the animal-vegetal axis. The direction
      of contraction defines an axis along which preexisting (such as the myoplasm) or
      newly created cytoplasmic domains are relocalized. Two microfilament-rich surface
      constrictions, the 'contraction pole' and the 'vegetal button' (which forms 20
      minutes later), appear along that axis approximately opposite the site where the
      contraction is initiated. The contraction pole can be situated as much as 55
      degrees from the vegetal pole, and its location predicts the site of
      gastrulation. It thus appears that in ascidian eggs, the organization of the egg
      before fertilization defines a 110 degrees cone centered around the vegetal pole
      in which the future site of gastrulation of the embryo will lie. The calcium wave
      and cortical contraction triggered by the entering sperm adjust the location of
      cytoplasmic domains along an axis within that permissive zone. We discuss the
      relation between that axis and the establishment of the dorsoventral axis in the
      ascidian embryo.

PMID- 7588076
TI  - Effect of polysialic acid on the behavior of retinal ganglion cell axons during
      growth into the optic tract and tectum.
AB  - We have demonstrated previously that the polysialic acid (PSA) moiety of the
      neural cell adhesion molecule (NCAM) can regulate peripheral nerve branching
      during development. In particular, it was found that specific enzymatic removal
      of PSA from motor axons causes them to form tight fascicles that are less
      responsive to normal guidance cues. In the present study, the role of PSA in the
      behavior of axons in the central nervous system has been examined through an
      analysis of chick optic axons during development. Unlike peripheral axons, which
      generally grow in a PSA-free environment, PSA was found to be present both on
      retinal ganglion cell axons and their environment in the tract and tectum.
      Furthermore, the enzymatic removal of PSA from the optic axons caused them to
      defasciculate in the tract/tectal region. This response was morphologically
      similar to targeting corrections made by these axons at a later stage when PSA
      levels have decreased, suggesting that the PSA may serve to shield them from
      responding prematurely to some guidance cues in their target region.

PMID- 7588077
TI  - The function of engrailed and the specification of Drosophila wing pattern.
AB  - The adult Drosophila wing (as the other appendages) is subdivided into anterior
      and posterior compartments that exhibit characteristic patterns. The engrailed
      (en) gene has been proposed to be paramount in the specification of the posterior
      compartment identity. Here, we explore the adult en function by targeting its
      expression in different regions of the wing disc. In the anterior compartment,
      ectopic en expression gives rise to the substitution of anterior structures by
      posterior ones, thus demonstrating its role in specification of posterior
      patterns. The en-expressing cells in the anterior compartment also induce high
      levels of the hedgehog (hh) and decapentaplegic (dpp) gene products, which
      results in local duplications of anterior patterns. Besides, hh is able to
      activate en and the engrailed-related gene invected (inv) in this compartment. In
      the posterior compartment we find that elevated levels of en product result in
      partial inactivation of the endogenous en and inv genes, indicating the existence
      of a negative autoregulatory mechanism. We propose that en has a dual role: a
      general one for patterning of the appendage, achieved through the activation of
      secreted proteins like hh and dpp, and a more specific one, determining posterior
      identity, in which the inv gene may be implicated.

PMID- 7588079
TI  - groucho and hedgehog regulate engrailed expression in the anterior compartment of
      the Drosophila wing.
AB  - Drosophila imaginal discs are divided into units called compartments. Cells
      belonging to the same compartment are related by lineage and express a
      characteristic set of 'selector genes'. The borders between compartments act as
      organizing centres that influence cell growth within compartments. Thus, in the
      cells immediately anterior to the anterior-posterior compartment boundary the
      presence of the hedgehog product causes expression of decapentaplegic, which, in
      turn, influences the growth and patterning of the wing disc. The normal growth of
      the disc requires that posterior-specific genes, such as hedgehog and engrailed
      are not expressed in cells of the anterior compartment. Here we show that
      hedgehog can activate engrailed in the anterior compartment and that both
      hedgehog and engrailed are specifically repressed in anterior cells by the
      activity of the neurogenic gene groucho. In groucho mutant discs, hedgehog and
      engrailed are expressed at the dorsoventral boundary of the anterior compartment,
      leading to the ectopic activation of decapentaplegic and patched and to a
      localised increase in cell growth associated with pattern duplications. The
      presence of engrailed in the anterior compartment causes the transformation of
      anterior into posterior structures.

PMID- 7588080
TI  - The pelota locus encodes a protein required for meiotic cell division: an
      analysis of G2/M arrest in Drosophila spermatogenesis.
AB  - During Drosophila spermatogenesis, germ cells undergo four rounds of mitosis, an
      extended premeiotic G2 phase and two meiotic divisions. In males homozygous for
      mutations in pelota, the germline mitotic divisions are normal, but the cell
      cycle arrests prior to the first meiotic division; pelota males are therefore
      sterile. Chromosomes begin to condense in these mutants, but other meiotic
      processes, including nuclear envelope breakdown and spindle formation, do not
      occur. The arrest phenotype closely resembles that of mutations in the Drosophila
      cdc25 homolog twine. Although meiosis is blocked in pelota and twine homozygotes,
      spermatid differentiation continues. pelota is also required for patterning in
      the eye and mitotic divisions in the ovary. We have cloned the pelota locus and
      show it encodes a 44 x 10(3) M(r) protein with yeast, plant, worm and human
      homologs.

PMID- 7588081
TI  - Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus
      homolog of dishevelled.

PMID- 7588082
TI  - Gender as a risk factor for adverse events to medications.

PMID- 7588085
TI  - Transnasal butorphanol. A review of its pharmacodynamic and pharmacokinetic
      properties, and therapeutic potential in acute pain management.
AB  - Butorphanol is a synthetic opioid agonist-antagonist analgesic with a
      pharmacological and therapeutic profile that has been well established since its
      launch as a parenteral formulation in 1978. The introduction of a transnasal
      formulation of butorphanol represents a new and noninvasive presentation of an
      analgesic for moderate to severe pain. This route of administration bypasses the
      gastrointestinal tract, and this is an advantage for a drug such as butorphanol
      that undergoes significant first-pass metabolism after oral administration. The
      onset of action and systemic bioavailability of butorphanol following transnasal
      delivery are similar to those after parenteral administration. The analgesic
      efficacy of transnasal butorphanol was generally superior to that of placebo in
      clinical trials in patients with moderate to severe postoperative pain or
      migraine headache. Results from single trials indicate that transnasal
      butorphanol provides pain relief comparable to that of intramuscular pethidine
      (meperidine) in postsurgical pain and comparable to or greater than intramuscular
      methadone in migraine headache. Moderate to severe musculoskeletal pain also
      appears to be responsive to transnasal butorphanol on the basis of results from 1
      small noncomparative study. Tolerability of transnasal butorphanol parallels that
      of the injectable form, with somnolence, dizziness, nausea and/or vomiting
      reported most frequently. Thus, transnasal butorphanol is a novel formulation of
      an established analgesic which appears suitable for the short term treatment of
      moderate to severe pain, especially in an ambulatory setting. Transnasal
      butorphanol is likely to provide an alternative to oral opioid analgesics,
      particularly in the presence of nausea or vomiting, or to parenteral opioids when
      the oral route of administration is not appropriate.

PMID- 7588086
TI  - Atovaquone. A review of its pharmacological properties and therapeutic efficacy
      in opportunistic infections.
AB  - Atovaquone has been investigated as an alternative agent for oral use in the
      treatment of both mild to moderate Pneumocystis carinii pneumonia (PCP) and
      toxoplasmosis, opportunistic infections commonly experienced by patients with
      AIDS. In patients with mild to moderate PCP, a dosage of 750mg 3 times daily
      (administered in tablet form) has similar overall therapeutic efficacy (defined
      as clinical response without a treatment-limiting adverse event) to the
      conventional therapies oral cotrimoxazole (trimethoprim-sulfamethoxazole) and
      intravenous pentamidine, respectively. Response rates to atovaquone are lower
      than those achieved with cotrimoxazole, but atovaquone has superior tolerability.
      Atovaquone recipients experienced significantly fewer treatment-limiting adverse
      effects than patients treated with cotrimoxazole (7 vs 20%) or pentamidine (4 vs
      36%). Mortality rates were higher among atovaquone-treated patients than in
      cotrimoxazole recipients (7 vs 0.6%) 4 weeks after completion of therapy in a
      large comparative trial, although most deaths were caused by bacterial
      infections. However, a similar rate of mortality was reported for atovaquone- and
      pentamidine-treated patients (16 vs 17% 8 weeks after discontinuation of therapy)
      in another study. In predominantly small numbers of patients with toxoplasmosis,
      of whom most were unresponsive to conventional agents, atovaquone 750mg 4 times
      daily (administered as tablets) produced a complete or partial radiological
      response rate of 37 to 87.5% 52% of patients achieved a complete or partial
      clinical response after 6 weeks of treatment in the largest trial (n = 87),
      although the incidence of toxoplasmosis-related death was 24% 18 weeks after
      therapy was initiated. Thus, atovaquone will be a useful option for the treatment
      of patients with mild to moderate PCP who are intolerant or unresponsive to
      cotrimoxazole, especially if the increased plasma drug concentrations observed
      with the suspension further improve response rates. Atovaquone should also be
      considered a promising agent for the treatment of toxoplasmosis.

PMID- 7588083
TI  - Alteplase. A reappraisal of its pharmacological properties and therapeutic use in
      acute myocardial infarction.
AB  - Alteplase (recombinant tissue-type plasminogen activator) stimulates the
      fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of
      intravenous alteplase in the early treatment of patients with acute myocardial
      infarction has been unequivocally proven, and recent results from the GUSTO trial
      indicate a significant advantage in 30-day survival for alteplase in an
      accelerated dosage regimen (< or = 100mg infused over 90 minutes rather than 3
      hours) over streptokinase. The advantage of the accelerated alteplase dosage
      regimen seems to be maintained for at least 1 year. The role of heparin as
      adjunctive therapy to thrombolysis remains to be fully defined but heparin
      administration appears to be more important in conjunction with alteplase than
      with streptokinase. Ideally, patients should receive alteplase as soon as
      possible after the onset of symptoms of acute myocardial infarction and, while
      therapy is most beneficial when administered early, survival is improved when the
      drug is administered up to 12 hours after symptom onset. The accelerated regimen
      of alteplase used in the GUSTO trial demonstrated a survival advantage in
      patients < or = 75 as well as those > 75 years of age which was at least as great
      as that seen with streptokinase. Similarly, alteplase reduces mortality in
      patients with both anterior and inferior infarctions; however, those with
      anterior wall infarctions show an improved outcome over those with inferior
      infarcts. On the basis of pharmacoeconomic analysis of GUSTO data, the
      accelerated alteplase regimen cost an estimated additional $US32,678 per year of
      life saved compared with a conventional streptokinase regimen. Cumulative 1-year
      costs were greater in patients who received the accelerated alteplase regimen but
      survival was significantly greater than in patients who received streptokinase.
      No difference in quality of life was evident in patients who received either
      treatment. The incidence of major haemorrhage associated with alteplase therapy
      appears to be similar to that seen with other fibrinolytic agents, increasing
      with increasing dose; however, the risk of stroke, particularly haemorrhagic
      stroke, is higher with alteplase than with streptokinase. Thus, alteplase has
      become firmly established as a first-line option in the management of acute
      myocardial infarction. On the basis of accumulated evidence, the greatest risk
      reduction with alteplase therapy may be in certain high risk groups, such as
      those with anterior infarcts, selected elderly patients and those who present
      late after symptom onset.

PMID- 7588088
TI  - Guidelines for the use of zidovudine in pregnant women with HIV infection.
AB  - Zidovudine therapy seems to be effective for reducing vertical transmission of
      HIV infection and preventing paediatric AIDS. Besides those cases in which it is
      indicated, zidovudine plays an important role in safeguarding maternal well
      being. Even though no data indicating teratogenic effect of this drug exist, its
      use during the first trimester should be limited to those cases where it is
      absolutely indicated. All undergoing this therapy should be informed that no
      information regarding the long term effects of this drug are available yet.
      Further controlled studies are necessary if this drug is to be used in those
      cases where it could actually be of benefit.

PMID- 7588087
TI  - Thrombolytic agents in development.
AB  - The quest continues for thrombolytic agents with a higher thrombolytic potency,
      specific thrombolytic activity and/or a better fibrin selectivity. Several lines
      of research towards improvement of thrombolytic agents are being explored,
      including the construction of mutants and variants of plasminogen activators
      (PAs), chimaeric PAs, conjugates of PAs with monoclonal antibodies, and PAs from
      animal or bacterial origin. Some of these new thrombolytic agents have shown
      promise in animal models of venous or arterial thrombosis and in pilot clinical
      studies. Such molecules include numerous mutants of tissue-type PA (t-PA) with
      prolonged in vivo half-life and/or resistance to protease inhibitors, and
      chimaeric PAs consisting of different regions of t-PA and of urokinase-type PA (u
      PA). Several molecular forms of the thrombolytic substance in the saliva of the
      vampire bat have been characterised and cloned. Vampire bat PA exhibits 85%
      homology to human t-PA but lacks kringle 2 and the plasmin-sensitive cleavage
      site. A thrombolytic enzyme of 203 amino acids is present in the venom of a
      southern copperhead snake. This polypeptide, termed fibrolase, is now produced by
      recombinant technology. Fibrolase does not activate plasminogen or protein C, but
      directly degrades the alpha and beta chains of fibrin and fibrinogen. Recombinant
      staphylokinase is not an enzyme, but it forms a 1:1 stoichiometric complex with
      plasminogen, which becomes active after conversion of plasminogen to plasmin. It
      is a potent and highly fibrin specific thrombolytic agent in animals and
      patients.

PMID- 7588089
TI  - Skin cancer. Recognition and treatment.
AB  - There is a worldwide increasing incidence of all forms of skin cancer among
      Whites as a result of increased sun exposure. Basal cell and squamous cell
      carcinomas, the most common tumours of the head and neck, are relatively benign
      neoplasms of elderly individuals. Malignant melanoma, however, has the potential
      for early metastasis and may occur in early adult life. The increase in malignant
      melanoma is particularly disturbing, and is a clear indication for skin screening
      clinics. Although surgical excision is the primary treatment of choice for skin
      tumours, various drugs may be of therapeutic value. Fluorouracil cream is a
      useful treatment for solar keratoses. Retinoids are particularly suitable for
      patients with large numbers of nonmelanoma skin cancer lesions and solar
      keratoses. For malignant melanoma, arterial limb perfusion with high
      concentrations of cytotoxic drugs may be performed both as an adjunctive and
      therapeutic manoeuvre. Treatment of metastatic melanoma with cytotoxic agents is
      associated with low response rates and high toxicity. However, trials with
      combined interferon-alpha, interleukin-2 and cytostatic drugs have produced
      promising preliminary results.

PMID- 7588084
TI  - Sulfasalazine. A review of its pharmacological properties and therapeutic
      efficacy in the treatment of rheumatoid arthritis.
AB  - Sulfasalazine was first used for rheumatic polyarthritis in the 1940s and in the
      past 2 decades has become firmly established as a disease-modifying antirheumatic
      drug (DMARD). The drug is split by the action of bacterial azoreductases in the
      large intestine into sulfapyridine and mesalazine (mesalamine, 5-aminosalicylic
      acid), although whether the parent molecule or the sulfapyridine moiety, or both,
      is the active principle remains uncertain. Sulfasalazine is an effective
      treatment for rheumatoid arthritis (RA), producing improvements in disease
      parameters similar to those seen with penicillamine, hydroxychloroquine or oral
      or parenteral gold in comparative clinical trials. However, there are no direct
      comparisons of the drug with methotrexate. Most adverse events associated with
      sulfasalazine are minor and tend to occur within 3 months of starting therapy. A
      meta-analysis of studies investigating DMARD therapy, which included almost 5000
      evaluable patients, concluded that sulfasalazine was close to methotrexate in
      terms of efficacy but was slightly less well tolerated. However, unlike
      sulfasalazine, many DMARDs may be unsuitable for women who are, or may become,
      pregnant because of their potential to cause teratogenic effects. Sulfasalazine
      may also offer a more rapid onset of action than other DMARDs and may slow down
      the radiological progression of RA. Combination therapy with other DMARDs,
      particularly methotrexate, appears more effective than single DMARD therapy. If
      the safety of these regimens is shown in large numbers of patients they are
      likely to become more widely used in the future. Sulfasalazine is a therapy of
      first choice in patients with RA and may be the DMARD of choice in women who are,
      or may become, pregnant.

PMID- 7588090
TI  - A guide to the treatment of lower respiratory tract infections.
AB  - Acute bronchitis is usually a viral infection which, unless there is a special
      disposition, does not require antibiotic therapy. For the initial oral
      chemotherapy of bacterial infections of the lower respiratory tract (chronic
      bronchitis, pneumonia) the effective and well tolerated cephalosporins,
      macrolides and amoxicillin plus beta-lactamase-inhibitor are recommended. In
      complicated cases with severe underlying disease, longer history or frequent
      exacerbations, quinolones should be given if Gram-negative infections are
      suspected or if initial therapy with other substances has failed. If Legionella,
      Mycoplasma or Chlamydia spp., so-called 'atypical' pathogens, are involved,
      macrolide antibiotics are the therapy of first choice. Special attention should
      be given to the increase in resistance against cotrimoxazole (trimethoprim
      sulfamethoxazole) and tetracyclines. In hospitals where primary pneumonias are
      treated preferentially by intravenous medication, therapy should be switched to
      oral antibiotics as soon as feasible (follow-up therapy). For severely ill
      patients with secondary pneumonia and underlying disease, second generation
      cephalosporins with aminoglycosides, or monotherapy with third generation
      cephalosporins are recommended. In very severe, high-risk cases, third generation
      cephalosporins, combinations with high-dosage quinolones or ureidopenicillins
      plus beta-lactamase-inhibitors are suitable. Future development in the antibiotic
      treatment of respiratory infections will follow the current trend of lower
      dosages, with the clear objective of shortening treatment periods and achieving
      earlier discharge from hospital.

PMID- 7588095
TI  - [Health risks associated with the use of anabolic steroids].

PMID- 7588097
TI  - [Hormones].

PMID- 7588094
TI  - [Current trends in hormone therapy during menopause and postmenopause].

PMID- 7588093
TI  - [Multiple usages for antiprogestins].

PMID- 7588096
TI  - [Inhibin and activin].

PMID- 7588098
TI  - [What is new about hormones?].

PMID- 7588099
TI  - [Hormone laboratory of the future].

PMID- 7588100
TI  - [Can type 1 diabetes mellitus be prevented?].

PMID- 7588101
TI  - [Hormone-dependent cell death].

PMID- 7588102
TI  - [Evolution of the endocrine system].

PMID- 7588103
TI  - [Growth factors and cytokines as messengers of hormonal effects].

PMID- 7588091
TI  - Antiplatelet drugs. A comparative review.
AB  - Antiplatelet therapy has become a useful means of preventing acute thromboembolic
      artery occlusions in cardiovascular diseases. The rationale for this is an
      enhanced activity of circulating platelets and release of platelet-derived
      vasoactive mediators, probably due to endothelial dysfunction. This review
      discusses the current status of 4 major classes of antiplatelet compounds: (i)
      aspirin and related drugs active via cyclo-oxygenase product formation; (ii)
      thienopyridines (ticlopidine and clopidogrel); (iii) direct thrombin inhibitors
      (e.g. hirudin); and (iv) GPIIb/IIIa receptor antagonists [e.g. abciximab (c7E3
      Fab)]. It is concluded that aspirin is the drug of choice for long term oral
      treatment, specifically for secondary prevention of myocardial infarction, and is
      also a suitable basic but not maximally efficient drug in percutaneous
      transluminal coronary angioplasty (PTCA) and platelet activation during clot
      lysis. Ticlopidine has a similar indication and may be superior to aspirin in
      prevention of ischaemic stroke and peripheral arterial occlusion. Direct thrombin
      inhibitors and glycoprotein GPIIb/IIIa receptor antagonists need further
      investigation in clinical trials. To date, these compounds have a higher bleeding
      risk and currently they are available only for short term parenteral application.
      They are superior to aspirin in acute platelet-dependent ischaemic syndromes,
      such as unstable angina, and in connection with therapeutic PTCA because of their
      high potency in preventing platelet-dependent reocclusion. Future developments
      include more selective thromboxane inhibitors, i.e. combined-mode agents;
      nonpeptide clot-specific thrombin inhibitors with longer lasting action and
      nonpeptide fibrinogen receptor antagonists.

PMID- 7588104
TI  - [Pitfalls in hormone assays].

PMID- 7588108
TI  - [Growth hormone therapy].

PMID- 7588107
TI  - [Blood vessel endothelium as an endocrine organ].

PMID- 7588106
TI  - [Licorice, aldosterone and blood pressure].

PMID- 7588105
TI  - [Does a clinician need autoimmune assays of the thyroid gland?].

PMID- 7588109
TI  - [Should oral contraceptives be available without prescription?].

PMID- 7588110
TI  - [Towards more individualized parenteral gold therapy].

PMID- 7588111
TI  - [Semi-automatic external defibrillators].

PMID- 7588114
TI  - [Human brain function makes magnetic resonance imaging live].

PMID- 7588113
TI  - [Participation of women in cervical cancer screening].

PMID- 7588116
TI  - [Severe tracheopathia osteochondroplastica in a young male].

PMID- 7588092
TI  - Meropenem. A review of its antibacterial activity, pharmacokinetic properties and
      clinical efficacy.
AB  - The parenteral carbapenem meropenem is relatively stable to inactivation by human
      renal dehydropeptidase (DHP-1) and does not require concomitant administration of
      a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial
      activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic
      pathogens being highly susceptible to the drug. Meropenem has shown clinical and
      bacteriological efficacy in the treatment of a wide range of serious infections
      in adults and children which is at least comparable with that of currently
      available treatment options. Its clinical and bacteriological efficacy is similar
      to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus
      metronidazole in the treatment of intraabdominal infections; cefotaxime or
      ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime
      with or without an aminoglycoside, in lower respiratory tract infections; and
      imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections.
      Satisfactory clinical and bacteriological response rates have also been achieved
      in patients with skin and skin structure infections, obstetric and gynaecological
      infections or septicaemia, and in immunocompromised patients with febrile
      episodes. Preliminary findings also indicate efficacy in the treatment of
      respiratory tract infections in patients with cystic fibrosis. The tolerability
      profile of meropenem is generally similar to that of comparator agents, although
      it is associated with a lower incidence of adverse gastrointestinal effects
      (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of
      seizures in patients with meningitis is not increased following administration of
      meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for
      the treatment of a wide range of infections including polymicrobial infections in
      both adults and children, with comparable efficacy to imipenem/cilastatin and
      various other treatment regimens. Meropenem is likely to be of greatest value as
      empiric monotherapy in the treatment of serious infections for those caused by
      multiply-resistant pathogens. Further clinical experience is necessary, however,
      to ultimately define its place in therapy.

PMID- 7588117
TI  - [Many specialties--dangerous additional effects?].

PMID- 7588115
TI  - [Pulmonary arteriovenous malformation causing an abnormally high hemoglobin
      concentration].

PMID- 7588118
TI  - [Nephropathia epidemica with pleuritis].

PMID- 7588119
TI  - [The treatment of LED-nephritis].

PMID- 7588122
TI  - [Are behavioral disorders in children and adolescents actually post-traumatic
      stress disorders?].

PMID- 7588112
TI  - [Social networks and social support as health resources].

PMID- 7588121
TI  - [Recurrent coma, computerized tomography findings in the brain and ECG changes].

PMID- 7588123
TI  - [Should stocks of smallpox virus be destroyed].

PMID- 7588120
TI  - [Diagnosis and treatment of headache in childhood].

PMID- 7588124
TI  - [To treat a cardiac arrest or to count ventricular arrhythmias?].

PMID- 7588125
TI  - [Oxygen radicals and asthma].

PMID- 7588127
TI  - [How to calculate the growth rate of a neoplasm?].

PMID- 7588129
TI  - [Accessory nerve injury as a complication of therapeutic stretching of the
      shoulder].

PMID- 7588128
TI  - [Screening for microalbuminuria in diabetic patients using a single voided urine
      specimen].

PMID- 7588126
TI  - [How much does my patient drink?].

PMID- 7588131
TI  - [Infertility in a woman with Kartagener syndrome].

PMID- 7588130
TI  - [Videofluorography as a method of evaluating hypernasality].

PMID- 7588133
TI  - [Assessment of adverse reactions to food].

PMID- 7588132
TI  - [Endometriosis treatment].

PMID- 7588134
TI  - [Hallucinations in hysterical psychosis].

PMID- 7588136
TI  - The diagnosis and management of migraine.

PMID- 7588135
TI  - [Hallucination as a conversion symptom].

PMID- 7588137
TI  - Efficacy and tolerability of oral sumatriptan in the treatment of acute migraine.
AB  - An open prospective study of the efficacy and tolerability of oral sumatriptan in
      the treatment of acute migraine attacks at the Kenyatta National Hospital,
      Nairobi, Kenya, is presented. Thirty two patients were initially recruited and 24
      completed the trial giving a drop-out rate of 25%. The age range was 17 to 55
      years with a mean of 35 years. Sumatriptan was found to be effective in 22 (92%)
      out of 24 patients. Side effects occurred in 38% (9/24) patients. These were mild
      and transient and included nausea, vomiting, numbness of limbs, fever and a
      feeling of heat in the head. It is concluded that oral sumatriptan is an
      effective drug in the treatment of acute migraine headaches. It has few side
      effects and is well tolerated by majority of patients.

PMID- 7588138
TI  - Pharmacokinetics of temazepam in male surgical patients.
AB  - The pharmacokinetics of temazepam, the 3-hydroxy1 derivative of diazepam, were
      studied in nine male surgical patients (age: 28-57 years; weight: 55-87 kg) who
      had ingested single 40 mg doses, 4 hours prior to minor surgical procedures. Peak
      plasma temazepam concentrations were achieved rapidly (within 1 h post drug
      administration) and the estimated volume of distribution (mean: 1.13 1/kg), total
      clearance (mean: 1.6 ml/min/kg) and terminal elimination half-life (mean: 8
      hours) were comparable to previously reported values in healthy subjects. There
      was no correlation between volume of distribution and either weight or age, and
      between clearance and age. These findings are broadly consistent with previous
      reports from studies in healthy subjects. Temazepam can therefore be used as a
      premedicant in patients requiring minor surgery; the concomitant anaesthetic
      agents administered and the surgical procedures have no effects on temazepam
      pharmacokinetics.

PMID- 7588139
TI  - Urinary symptoms and blood pressure of children with Schistosoma haematobium
      infection in south-eastern Nigeria.
AB  - The urinary symptoms and blood pressures of 510 children (aged 5-15 years) with
      Schistosoma haematobium infection in Ijiman community, Cross River State of
      Nigeria, were studied in 1992. The prevalence rate of infection was 44%, a
      majority of the children presenting with light infection. Significant symptoms
      were visible haematuria, dysuria, suprapubic pain and strangury. The sensitivity
      and specificity of these symptoms were too low for them to be recommended as
      distinct clinical diagnostic criteria. The impact of the disease could not be
      demonstrated on blood pressures of the children. Nevertheless, urgent control
      measures with emphasis on the provision of ventilated improved pit toilets and
      potable water are strongly recommended for the control of the disease as
      persistent infection is known to mask manifestation of severe complications till
      an older age.

PMID- 7588140
TI  - Prevalence of hepatitis B virus markers among drug-dependent patients in Jeddah
      Saudi Arabia.
AB  - The purpose of this study was to determine the prevalence of HBV markers-
      hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen
      (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) among drug
      dependent patients in Jeddah, Saudi Arabia. Over a period of four months, all the
      patients admitted for drug dependence were tested for these HBV markers. There
      were 349 patients altogether of which 281 (80.5%) were intravenous drug users. 44
      were positive for HBsAg, 171 were positive for anti-HBs and 187 were positive for
      anti-HBc, giving an overall prevalence of 12.6%, 49.0% and 53.6%, respectively.
      The prevalence of each marker was higher among the IV drug users. The high
      prevalence of the markers indicate that HBV is highly endemic among drug
      dependent patients in this city, especially among the IV drug users and that
      almost half of all the patients have developed some immunity to the virus. Many
      of the drug-dependent HBsAg carriers also possess HBeAg. The persistence of these
      two antigens makes them highly infectious and predisposes them to chronic liver
      diseases and hepatocellular carcinoma. There is a need for more public education
      and needle and syringe exchange schemes to control the spread of the virus and
      prevent future complications.

PMID- 7588141
TI  - Bancroftian filariasis: profile of serum antifilarial antibody and circulating
      parasite antigen.
AB  - Forty-five serum specimens collected from persons living in a filaria-endemic
      community in Maili Nane, Coastal Kenya were analyzed by ELISA for levels of
      isotype specific antifilarial antibody and by Og4C3 ELISA for circulating
      parasite antigen. Mean levels of IgG1, IgG2, and IgG3 were lower in
      microfilaraemic persons than in amicrofilaraemic individuals. In contrast, mean
      levels of antifilarial IgG4 were significantly higher in microfilaraemic persons
      (p = 0.0374). Serum samples from all microfilaremic persons were positive for
      circulating antigen as were 15% of samples from amicrofilaremic and asymptomatic
      persons. The Og4C3 antigen assay may have value as a technique for identifying
      and targeting communities for control efforts.

PMID- 7588142
TI  - Congenital malformations in Gondar Hospital, Ethiopia.
AB  - A retrospective record analysis of the last six years was done to determine the
      pattern of congenital malformations in the paediatrics department of Gondar
      College of Medical Sciences Hospital, North Gondar, Ethiopia. Of a total of 7489
      admissions, 191 cases of congenital malformations were found, accounting for
      about 2.6% of the total admissions. The male to female ratio was 2.7:1. Cardiac
      malformations were seen more frequently (31%) followed by hernias (15.7%) and
      gastrointestinal malformations (14.8%). In only 45% of the cases were medical
      care sought in the first year of life. Out of 191 cases, 20 died in which the
      malformations were directly or indirectly accountable, giving a case fatality
      rate of around 10.5%. This study has highlighted the need for a community based,
      large scale prospective study to determine the incidence and contributory factors
      for congenital malformations.

PMID- 7588143
TI  - Anaemia in pregnancy: perceptions of patients in Dar-es-Salaam.
AB  - This study was performed to assess the pregnant women's knowledge and attitudes
      towards anaemia, its causes, prophylaxis, and treatment and to describe existing
      problems with interventions for anaemia in antenatal clinics. A total of 310
      women were interviewed from three MCH-clinics in suburban Dar-es-Salaam. Anaemia
      was considered a major problem by 88% and 75%, respectively in the two peripheral
      MCH clinics, but by only 44% of attenders in the hospital MCH clinic. Over 85% of
      interviewees were aware of the causes of and ways of preventing anaemia. The most
      frequently mentioned cause of anaemia were related to nutrition while intestinal
      parasites was mentioned by a few women. Only 5% believed that anaemia might not
      be dangerous for the mother. In all three clinics more than 90% were aware of the
      advantages of early booking for antenatal care. None of the mothers had received
      any ferrous supplements during the current pregnancy, and only a minority (38%)
      in the previous pregnancy though 40% of them said they were informed they had
      anaemia in the previous pregnancy. Side effects were not reported as a reason for
      non-compliance. Thus, mothers were aware that anaemia is a health problem in
      pregnancy. They would accept effective intervention if they were offered them.
      The irregular and inadequate supply of haematinics to antenatal clinics is a far
      more important obstacle to the implementation of the anaemia prevention programme
      than the knowledge and attitudes of the mothers.

PMID- 7588144
TI  - Value of rebound tenderness in acute appendicitis.
AB  - This is a prospective study on 123 randomly selected patients admitted with the
      diagnosis of acute appendicitis. The value of rebound tenderness as a clinical
      diagnostic tool was statistically compared to those of some other physical signs;
      namely guarding, rigidity and Rovsing's sign. Rebound tenderness was found to
      carry the highest sensitivity (94.7%), negative predictive value (81.3%),
      reliability (49.1%), and association with histological diagnosis (P < 0.05).
      However, its specificity and positive predictive value was not significantly
      different from those of other physical signs. It is concluded that, in
      contradistinction to some previously published reports, our study emphasizes the
      role of rebound tenderness in the clinical diagnosis of acute appendicitis.

PMID- 7588146
TI  - Oestrogen and progesterone receptor status and PgR/ER ratios in normal and
      myomatous human myometrium.
AB  - The concentration and molecular properties of the oestrogen (ER) and the
      progesterone (PgR), present in normal myometria and uterine leiomyometria,
      obtained from a group of age-matched, pre-menopausal, negroid female patients
      were investigated. Serum oestrogen and progesterone levels did not differ
      significantly in the two groups. Significant differences were detected in ER and
      PgR levels between normal and leiomyomatous myometria. Both ER (154%; p < 0.0001)
      and PgR (33%; p < 0.05) were significantly increased in uterine leiomyomas. PgR
      levels were less affected than the ER levels, causing a significant decrease
      (44%; p < 0.05) in the PgR/ER ratio in myomatous myometria. Dissociation and
      sedimentation constants, as well as iso-electric points of ER and PgR were
      essentially similar in normal and in myomatous myometria. According to our
      results, tissue pathology does not appear to be associated with defects in the
      molecular properties of ER and PgR, but with differential changes in the ER and
      PgR levels, subsequently affecting the PgR/ER ratio.

PMID- 7588145
TI  - Factors associated with neonatal tetanus mortality in northern Nigeria.
AB  - Over a 12-month period, a cluster survey on Neonatal tetanus (NNT) mortality was
      conducted in Northern Nigeria. The relative contributions of knowledge, attitude
      and practice (KAP) to certain epidemiological factors associated with NNT deaths
      were evaluated. NNT mortality was 20.6/1000 live-births (i.e. over 65% of
      neonatal mortality). Poor cord management showed the strongest association with
      NNT mortality with comparable contributions from KAP. Less than 40% of 2,623 live
      births recorded during the survey followed two or more ante natal visits. This
      was significantly associated with NNT mortality with virtually equal
      contributions from KAP. Over 60% of the births had traditional surgeries
      performed with highly significant association with NNT mortality. Knowledge
      deficit was the most important contributor to performance of traditional
      procedures. Tetanus toxic coverage (32.0%) was also associated with NNT mortality
      with knowledge and attitudinal deficits accounting for over 75% of poor coverage.
      Most deliveries were outside hospitals and related facilities with highly
      significant association with NNT deaths. Attitude and practice contributed over
      80% to this observation. In view of the associated epidemiological factors, and
      the relative roles of KAP, community--specific prevention strategies are
      suggested. Training and involvement of traditional birth attendants is
      emphasized. Domicilliary service are also suggested in view of the widely
      practised purdah system.

PMID- 7588147
TI  - Epidemiology of HIV infection among long distance truck drivers in Kenya.
AB  - A total number of two hundred eighty three long distance truck drivers and their
      assistants (loaders) who ferry goods between Kenya and Zaire were included in a
      cross-sectional study between September 1991 and April 1992. Twenty six percent
      of the study subjects were seropositive for HIV-1 and none were HIV-2
      seropositive. Countries of birth and residence were significantly associated with
      HIV infection (X2 = 23.6, P = 0.0006). Significant associations were also found
      between HIV seropositivity and level of education from secondary school and above
      (OR = 3.4, 95% C.I. = 1.01-11.55); being circumcised was more protective, (OR =
      0.38; 95% C.I. = 0.19-0.76), history of many years of driving (X2 = 9.3, p =
      0.0254) and income (OR = 11.13, 95% C.I. = 1.35-91.95). When a stepwise multiple
      logistic regression model was fitted to all the variables observed to be
      significant in the univariate analysis, the following risk factors attained
      statistical significance: lack of circumcision (OR = 3.75); income greater than
      Ksh. 2000 (OR = 7.24); being employed in long distance driving more than 11 years
      (OR = 3.98); and secondary school education and above (OR = 4.06, 95% C.I. = 1.18
      13.98). Reference for all the above Odds Ratios was 1.

PMID- 7588148
TI  - Experimental immunization against cutaneous leishmaniasis using Leishmania major
      subcellular fractions alone or in combination with Phlebotomus duboscqi gut
      antigens.
AB  - Leishmania major-derived flagella and nuclear fractions, and a combination of
      flagella and sand fly gut antigens were assessed for protection against L. major
      infection in BALB/c mice. Mice immunized with flagella antigen developed a severe
      infection while nuclear fraction-immunized animals were partially protected at
      the onset of infection from week 1 to 4 post challenge. A combination/cock tail
      of flagella and sand fly gut antigens protected animals at a later stage from
      week 10 to 14 post-infection. Surviving cocktail-immunized animals did not
      ulcerate, and parasites did not metastasize to the viscera. These results provide
      preliminary evidence of the potential of a cock tail antigen derived from
      Leishmania flagella and sand fly gut in the protection against cutaneous
      leishmaniasis caused by L. major.

PMID- 7588150
TI  - Epidemiology of human hookworm and Ascaris lumbricoides infestations in rural
      Gambia.
AB  - In a cross-sectional study of helminth infections in a rural village in The
      Gambia, West Africa, hookworm, probably Necator americanus and Ascaris
      lumbricoides were found to be the most prevalent helminths present at prevalence
      levels of 30% and 25% respectively. Other parasites present were Trichuris
      trichiura (2.4%) and Schistosoma mansoni (1.5%). The mean egg counts of N.
      americanus and A. lumbricoides in all age groups and in the total population were
      low. Egg counts between age and sex groups were not statistically significant.
      The frequency distributions of both N. americanus and A. lumbricoides were
      overdispersed with the majority of the sample population producing none or few
      eggs, and a small minority producing relatively large amounts of eggs. Large
      variance: mean ratios within age groups and the total study population suggested
      a high degree of aggregation of the parasites in this community.

PMID- 7588149
TI  - Anthropometric measurement in children aged 0-6 years in a Nigerian village.
AB  - Seven hundred and three Nigerian village children in their first six years of
      life were subjected to anthropometric measurements and physical examination in
      early 1988. The heights of 66.9% and weights of 60.5% of them fell below the
      third percentile of a Nigerian equivalent for international reference population
      standard. Mid upper arm circumference values indicated moderate to severe
      malnutrition in over 25% of all 1-5 year old children surveyed. Fever, cough,
      headache and diarrhoea were the commonest symptoms encountered in the children.
      Mild pallor of the conjunctival mucosa and physical signs of protein energy
      malnutrition were commonly seen. Fungal and septic skin lesions were present in
      11.45 and 11.1% of the children respectively, whilst rhinorrhoea was seen in
      4.7%, otitis media in 6% and pharyngotonsillitis in 3.3%. Thirty four (4.8%) of
      the children had haemic whereas five had pathological murmurs. Dental calculi
      were present in 15.8%, umbilical herniae in 18.2%, hepatomegaly in 48.2% and
      splenomegaly in 23% of the children. Seven (1%) had cerebral palsy. The
      implication is that malnutrition, sickle cell disease, malaria and other
      infections are the prevailing causes of morbidity in the preschool aged children
      surveyed. Desirable improvements include upgrading socio-economic and living
      conditions and instituting appropriate control measures.

PMID- 7588151
TI  - Agrochemicals exposure and health implications in Githunguri location, Kenya.
AB  - A study conducted in a rural agricultural community (Githunguri location) in
      Kenya between 1987 and 1990 investigated the extent of use of agrochemicals,
      especially pesticides, by the farmers; their level of awareness of the dangers
      posed by these chemicals and their attitudes towards agricultural chemicals in
      general. The findings showed that more than 95% of the farmers used pesticides
      extensively. More women than men were found to be at risk of agrochemicals
      exposure, while babies and children were at more risk of agrochemicals exposure
      than the women. In this community, knowledge and awareness regarding safety in
      handling and storage of agrochemicals was to some extent limited. For instance,
      many had no knowledge of an antidote in case of accidental poisoning.
      Additionally, suicidal attempts by ingestion of agrochemicals was prevalent.
      Improper handling of the agrochemicals by the community members was implicated to
      have adverse health effects. These health effects were reported in form of
      complaints. They ranged from acute to chronic conditions. Consequently, an
      intervention programme was launched with the women as the key players. It is
      envisaged that community participation in the on going intervention programme is
      saving babies, children, women and the community at large from agrochemicals
      hazards.

PMID- 7588153
TI  - Munchausen's syndrome: case report.
AB  - A case report of a 31-year old butcher with haemorrhagica histrionica is
      presented. The patient went to great lengths to induce haematemesis and fake its
      symptoms to gain admission to hospital. The alarming frequency of admissions and
      dramatic behaviour of the patient prompted this report.

PMID- 7588154
TI  - Management of difficult intra operative bleeding by abdominal packing: report of
      four cases.
AB  - Difficult perioperative bleeding in four obstetric and gynaecology patients was
      managed with temporising abdominal packs left in place with abdominal closure for
      48-72 hours in order to avoid deaths on the operating table when blood loss could
      not be adequately replaced and hemostasis could not be secured. Abdominal re
      opening to remove the packs was undertaken. Three of the patients were eventually
      discharged home after satisfactory recovery. The fourth died of sepsis three
      weeks after the fourth re-operation and bilateral internal iliac artery ligation.
      Abdominal packing thus has a place in the management and salvage of patients with
      difficult obstetric and gynaecologic perioperative bleeding.

PMID- 7588155
TI  - Rebound tenderness in the clinical diagnosis of acute appendicitis.

PMID- 7588152
TI  - The management of severe malaria in children: a review.
AB  - We have attempted to summarise an approach to management of severe malaria from
      our experience and that of others from published data in this review. This
      represents our current state of knowledge and practices which may change as
      research continues in this field. It also represents what we feel should be the
      minimum aim in treating severe malaria even at district hospital level. It
      focuses on practical issues encountered when admitting such patients: initial
      assessment, immediate supportive management, use of transfusion, appropriate anti
      malarial treatment and ongoing management.

PMID- 7588157
TI  - Differences in cord serum retinol concentrations by ethnic origin in the Negev
      (southern Israel).
AB  - Subclinical vitamin A deficiency is related to increased morbidity and mortality
      in infants and children. Previous studies indicate that the traditional diet of
      Moslem Bedouins, an important ethnic group in Southern Israel, is low in vitamin
      A content. Cord serum retinol (vitamin A) concentration was measured by HPLC in
      samples from 251 apparently healthy (birth weight > 2500 g, gestational age > 37
      weeks) neonates with no abnormal perinatal events, 138 Jews and 113 Bedouins.
      Retinol < 15 micrograms/dl was measured in a total of 14% of infants: in 7% of
      Jewish and 26% of Bedouin newborns (P < 0.001). However, mean cord serum retinol
      was only slightly lower in Bedouins than in Jews (30 +/- 26 vs. 37 +/- 27
      micrograms/dl mean +/- S.D., n.s.). Cord serum retinol was not related to
      socioeconomic indices. Cord serum retinol < 15 micrograms/dl was measured in 25%
      and in 12% of infants with birth weight less than and equal or greater than 3000
      g, respectively (P = 0.01), and in 28% and 13% of infants with gestational age 37
      38 weeks and 39-41 weeks, respectively (P = 0.03). Low cord serum retinol was
      found to be prevalent in Southern Israel, particularly in Bedouin infants. In the
      population of healthy neonates studied, very low cord serum retinol
      concentrations were found more frequently in infants born with a lower weight
      and/or after a shorter gestation.

PMID- 7588156
TI  - Fetal and postnatal growth to age 2 years by mother's country of birth.
AB  - The objective of this study was to measure the physical growth of fetuses and
      infants in an inner city health district in the north of England and to compare
      their growth profiles according to mother's country of birth (British Isles or
      Indian subcontinent). The study was part of the Central Manchester Child Growth
      Project, a prospective longitudinal study of fetal and postnatal growth and
      development in a sample from the geographically-defined Central Manchester Health
      District. Data were collected from the beginning of the second trimester of
      pregnancy to the age of 2 years. One-hundred seventy-four singleton infants born
      at term ( > or = 37 weeks) had serial antenatal cephalometry every 3 weeks from
      the beginning of the second trimester and had serial head, length and weight
      measurements at birth and at the ages of 6, 13, 26, 52 and 104 weeks. Infants of
      Indian-born mothers tended to be lighter at birth than those of locally-born
      mothers, but the difference was not due to lower accumulation of soft tissue.
      Body length from 6 to 52 weeks in both groups of infants was similar. The major
      finding was the reduced head size in infants of Indian-born mothers, the
      difference being significant among boys, evident from mid-pregnancy and
      persisting postnatally to age 2 years. Reduced fetal growth is associated with
      the development of cardiovascular disease in adulthood, mortality from ischaemic
      heart disease being specifically linked with head size at birth. The reduced head
      size of boys of Indian-born mothers is of interest because male immigrants from
      the Indian subcontinent who live in England have an increased incidence of non
      insulin dependent diabetes and a substantial excess mortality (standardised
      mortality ratio 313 at ages 20-29) from ischaemic heart disease.

PMID- 7588158
TI  - Parents' estimation of psychomotor development in very low birthweight (VLBW)
      infants.
AB  - BACKGROUND: Within a longitudinal developmental surveillance project we tested
      the accuracy of the Revised Prescreening Developmental Questionnaire (R-PDQ) to
      detect developmental retardation in very low birthweight (VLBW) infants. METHODS:
      Seventy surviving VLBW-infants born between July 1992 and December 1993 were re
      examined at 6 months corrected age. The parent-completed questionnaires (n = 67)
      were compared with developmental assessment using the Griffiths Developmental
      Scale. RESULTS: At 6 months corrected age, normal results of the Griffiths
      Developmental Scale (developmental quotient > or = 81) were found in 61/67 (91%)
      VLBW-infants and in 45/67 (67%) questionnaires (no or one 'delay'). The parents
      identified all six infants with psychomotor retardation on the Griffiths
      Developmental Scale (co-positivity 100%). However, only 45/61 infants with normal
      development were so identified with the R-PDQ (co-negativity 74%, positive
      predictive value 27%). CONCLUSIONS: The R-PDQ discovered all infants whose
      developmental quotient was two standard deviations below the mean on the
      Griffiths Developmental Scale. The relatively high proportion of false positive R
      PDQ results corresponded to lower developmental quotients within the normal
      range. Therefore, the R-PDQ provides a useful screening instrument for VLBW
      infants.

PMID- 7588162
TI  - Xth International Congress of EMG and CLinical Neurophysiology. Kyoto, Japan,
      October 15-19, 1995. Abstracts.

PMID- 7588161
TI  - Antiviral therapy in neonatal chronic lung disease.
AB  - Infants born prematurely who develop chronic lung disease frequently suffer acute
      respiratory deteriorations. In a randomized trial, we assessed if treatment of
      such relapses with the antiviral agent Ribavirin increased the speed of recovery
      and improved lung function at follow-up. During the acute deterioration and its
      treatment, respiratory rate and requirement for respiratory support were
      recorded. Once discharged from hospital, respiratory symptoms and admissions for
      chest-related illnesses were documented. Infants were recalled at 6 months of age
      for lung function measurements. Forty-four infants (23 given Ribavirin), median
      gestational age of 26 weeks, completed the trial and had lung function
      measurements at 6 months. Although viral infections were identified in relatively
      few patients, the interim analysis demonstrated Ribavirin administration for 3
      days was associated with a greater reduction in respiratory rate and inspired
      oxygen concentration (P < 0.02). At follow-up, there was no significant
      difference between groups in the proportion of infants who were symptomatic or
      required re-admission to hospital for chest-related illnesses; the Ribavirin
      group, however, had lower airways resistance (P < 0.01) and higher specific
      conductance (P < 0.02). We conclude that antiviral therapy seems to speed the
      rate of recovery from acute respiratory deteriorations seen in preterm infants
      with chronic lung disease; this is associated with improved lung function, but
      not lower respiratory morbidity, at follow-up.

PMID- 7588160
TI  - The ontogeny of the glucose-6-phosphatase enzyme in human embryonic and fetal red
      blood cells.
AB  - We have shown for the first time that the microsomal glucose-6-phosphatase enzyme
      protein is present in human embryonic and fetal red blood cells and the ontogeny
      of its expression has been determined. In the earliest embryos, red cells are
      predominantly of the primitive megaloblastic type. Circulating red cells in the
      primitive megaloblastic series are predominantly nucleated and glucose-6
      phosphatase immunopositive. Non-nucleated, immunoreactive megaloblastic cells are
      in a minority. In fetuses > 12 weeks gestation, the erythrocytes are of the
      definitive normoblastic series and in the transitional period of switch-over in
      late embryonic-early fetal life, up to 30% of glucose-6-phosphatase
      immunopositive cells are definitive normoblastic in type, with a variable
      contribution from nucleated and non-nucleated cells. Thereafter, the number of
      immunopositive cells in the definitive normoblastic series decreases such that
      after 12 weeks gestation it is less than 5%. The fact that a predominantly
      hepatic protein in adults (glucose-6-phosphatase) is present in embryonic and
      fetal red blood cells, particularly nucleated red cells, raises the possibility
      of diagnosis of disorders of liver protein expression in nucleated fetal red
      cells isolated from the first trimester maternal circulation.

PMID- 7588159
TI  - Posterior fontanelle cranial ultrasound: anatomic and sonographic correlation.
AB  - OBJECTIVE: The purpose of this study was to correlate normal brain anatomy as
      seen on posterior fontanelle cranial sonography with anatomical sections of the
      premature infant brain. MATERIALS AND METHODS: Images obtained from 93 cranial
      ultrasound examinations performed via both the anterior and posterior fontanelle
      in 53 infants, ranging in gestational age from 24 to 42 weeks, were reviewed to
      determine the ultrasound anatomy visible and also the changing appearances with
      increasing gestational age. The brains of five infants were sectioned at post
      mortem according to predetermined anatomical landmarks to correlate with
      posterior fontanelle ultrasound scan planes. Brain preservation techniques
      involved fixation in formalin at room temperature, refrigeration of brain
      following formalin fixation, and brain freezing at -17 degrees C. RESULTS: In the
      premature infant brain, the subarachnoid space is up to 15 mm in thickness.
      Occipital lobe anatomy well seen includes occipital horns of lateral ventricles,
      and white matter tracts to the visual cortex and visual association areas. Brain
      anatomy was better appreciated on sections obtained following brain freezing
      rather than formalin fixation. CONCLUSION: Satisfactory ultrasound anatomic
      correlation of the premature brain is possible using a brain freezing
      preservation technique. Posterior fontanelle ultrasound allows detailed
      illustration of occipital lobe anatomy.

PMID- 7588164
TI  - [The TRIG (Texas Revised Inventory of Grief) questionnaire. French translation
      and validation].
AB  - Bereavement and mourning are normal reactions to the loss of a loved one,
      characterized by specific ideas, affects, and behavior, evolving spontaneously
      towards resolution. This syndrome, classified as a non mental disorder (DSM IV),
      resembles depression. Up to now, there was no instrument for an objective
      assessment. The general objective of this work was to present the french version
      of the Texas Revised Inventory of Grief, or TRIG (Faschingbauer, De Vaul &
      Zisook, 1981), designed to evaluate the intensity of the reaction to the loss of
      a loved one. Our population is composed of 154 adults of the general population
      (74 females and 80 males) of the age of 25 to 35 years. A principal component
      analysis gave us a general factor of grief (28% VT) which gathers emotional
      reaction to the bereavement. The factorial analysis with Varimax Rotations
      confirmed the existence of two specific types of grief. These are "past behavior"
      (reaction at the time of loss) factor (37% VT), "present feelings" (at the time
      of assessment by TRIG) factor (31% VT). Furthermore, another factor of "related
      facts" (32% VT) appeared to be in relation with the aptitude of coping. These
      results allowed us to construct a valid questionnaire of 25 items measuring 3
      types of bereavement reactions.

PMID- 7588163
TI  - [Clinical diagnosis and standardized evaluation of borderline personality:
      preliminary report].
AB  - A sample of 36 patients considered by French clinicians as suffering from a
      borderline personality disorder was evaluated using the International Personality
      Disorder Examination, the Diagnostic Interview for Borderline-Revised, and the
      Minnesota Multiphasic Personality Inventory. First, global descriptive analysis
      of the sample elicited the socio-demographic and standard clinical
      characteristics of the borderline individuals. After diagnostic evaluation, the
      sample appeared to be quite homogeneous with 25 of the 36 patients evaluated
      (69.5%) being defined as borderline by two of the three diagnostic systems: ICD
      10, DSM III-R and Gunderson (15/36 = 41.5% of patients were defined as borderline
      by all three systems). It is the types of BL personality co-diagnoses which
      differentiated the BL subjects in the sample from those classically described in
      the international literature, since the most frequent personalities were the
      Dependent and Avoiding ones, not the Antisocial, Histrionic, Narcissistic or
      Schizotypic personalities of the DSM III-R. ICD 10 elicited the same significant
      prevalence of Anxious and Dependent personalities. Lastly, the patients diagnosed
      as borderline both by clinicians and by all diagnostic systems (forming the
      sample "core") were compared with the rest of the sample with regard to socio
      demographic, clinical and diagnostic characteristics. A few hypotheses are
      proposed on the type of variables that may permit to discriminate between these
      two types of patients.

PMID- 7588165
TI  - [Grief experience by 154 young adults in the general population (value of the
      TRIG grief scale). Texas Revised Inventory of Grief].
AB  - 154 young adults (25-35 years old) of the general population completed tests and
      questionnaires in order to find correlations between the scores at the Texas
      Revised Inventory of Grief, TRIG (Faschingbauer et al. 1977) and several
      personality variables (depression, anxiety-state and -trait, self-esteem, locus
      of control, social support, and tobacco dependency). The correlation between all
      these variables are presented and discussed. TRIG, in its French translation and
      validation, proves to be a reliable and specific instrument in the assessment of
      bereavement (past and current distress, and coping process).

PMID- 7588166
TI  - [French translation of the Chapman Social and Physical Anhedonia Questionnaire:
      validation of the French translation in controls and schizophrenic patients].
AB  - Whereas Chapman's social and physical scales are the most used instruments for
      the assessment of anhedonia in schizophrenia, no French translation has been
      still validated by the authors. Therefore, the aim of this study was first to
      translate into French the both scales, and after back translation, to obtain the
      agreement of the original authors. Second, the aim was to establish values and to
      establish the cut-off beyond of which French subjects could be considered as
      anhedonic. One hundred and twenty-three subjects were included: 72 control
      subjects without mental disorders and 51 stable schizophrenic patients defined by
      the DSM III-R, ICD 9, ICD 10, RDC or Feighner criteria. According to the
      literature, schizophrenic patients had higher scores for both scales than control
      subjects (p < 0.001; Student t test). The social anhedonia scores are different
      due to cultural variations. The distribution of physical anhedonia scores in
      control subjects or in schizophrenic patients differed from normal distributions
      (respectively, p < 0.05; p < 0.0001; Shapiro-Wilks test). The distribution of
      social anhedonia scores differed from normal distributions (p < 0.01) only in
      schizophrenic patients but not in control subjects. By maximising the Younden
      indice [Sensitivity + Specificity -1], the cut-off of the physical anhedonia
      score was 18 (Younden indice = 0.45), and the cut-off of the social anhedonia
      score was 12 (Younden indice = 0.24). In using this cut-off, the French physical
      anhedonia scale had a good positive predictive value (evaluated by logistic
      regression) for schizophrenia. Therefore, a patient with a physical anhedonia
      score beyond 18 have a probability of 64% to be schizophrenic. In contrast, the
      social anhedonia scale was less discriminant for schizophrenia. Indeed, patient
      with a social anhedonia score beyond 12 have a probability of 52% to be
      schizophrenic. This French version of Chapman's anhedonia scales could be
      considered as an useful instrument to assess anhedonia, in particular physical
      anhedonia, in schizophrenic patients.

PMID- 7588167
TI  - [Anxious-depressive state and cognitive deficit in HIV infection].
AB  - This study tries to demonstrate the importance of using follow-up trials and
      taking anxio-depressive status into account while interpreting cognitive
      impairment in HIV-infected subjects. Subjects included were: 18 HIV carriers,
      mostly homosexual, belonging to CDC groups II (4), III or IVC2 (7) and IV (7),
      selected within a cohort of 63, as having been assessed 3 times, with no focal or
      identified brain disease at entry. Our methods were: 1) psychiatric interview
      based on DSM III-R criteria, clinical scales (Spielberger's STAXI and the MADRS)
      and cognitive questionnaires; 2) neuropsychological evaluation including 16
      subtests screening attention, memory, visuo-spatial function, motor dexterity,
      psychomotor speed, and language; 3) repeated assessment within a period ranging
      from 6 to 21 months. RESULTS: At entry, cognitive status was impaired for 14
      subjects (2 II, 5 III or IVC2, 7 IV). Disorders had disappeared for 7 subjects (2
      II, 2 IVC2 and 3 IV) at following assessments allowing us to conclude on a
      psychogenic origin. For 7 subjects, cognitive status had either remained constant
      (3 III and 2 II) or had worsened within 7 to 17 months (2 IV), whereas
      psychiatric symptoms had decreased, implying HIV encephalopathy. Follow-up trials
      including 3 neuropsychological and psychiatric assessments and neuroimagery, if
      necessary, were required to ascertain the causes of cognitive impairment
      consequently attributed to anxio-depressive symptoms or HIV encephalopathy in 14
      subjects.

PMID- 7588169
TI  - [Deficits in memory retrieval: an argument in favor of frontal subcortical
      dysfunction in depression].
AB  - While numerous studies have objective quantitative and qualitative deficits of
      memory in depressed patients, the mechanisms of these impairments are not well
      established. The study reported here was designed to assess encoding and
      retrieval processes in depression and to define the specific nature of memory
      failure associated with this disorder. METHODS: Ten inpatients with major
      depression responding to DSM III-R criteria and ten normal controls were included
      in this study. All subjects were assessed with a neuropsychological battery
      including: a) subtests of Weschsler memory scale (digit span, logical memory); b)
      verbal fluency (letter); c) two tasks assessing executive functions (cognitive
      estimate, Nelson's test); d) two explicit tasks of verbal learning (California
      Verbal Learning Test and Grober & Buschke's procedure) which measure memory
      performance in various conditions of encoding (incidental vs controlled) and of
      recollection (free recall, cued recall and recognition). Severity of depression
      was assessed with the MADRS and the Retardation Rating Scale for Depression.
      RESULTS: Although there was no difference between patients and controls on digit
      span and logical memory tasks, depressed patients exhibited a deficit in verbal
      learning with CVLT and Grober & Buschke's procedure. On California Verbal
      Learning Test, depressive subjects performed poorly in free recall and
      demonstrated poor consistency. Patients show free recall improvement across
      trials 1 or 5 and this learning effect didn't differ from controls. Score of
      patients and controls on cued recall and recognition were at the same level.
      Grober & Buschke's procedure confirmed these results. Despite a control of
      encoding processes during the initial presentation of the words, free recall
      measure revealed significant difference between groups. Like controls, patients
      recalled almost all items when semantic cues was provided and their recognition
      results showed a ceiling effect. Consistency indexes of free recall and cued
      recall differed significantly between groups. Verbal fluency and frontal tasks
      didn't allow to distinguish the depressive patients from controls. DISCUSSION:
      Depressive subjects exhibited a deficit in free recall and poor consistency while
      cued recall and recognition were normal. Patient's results in free recall are
      characterized by difficulties in planning and in maintaining retrieval
      strategies. These findings suggest that memory failure in depression could
      reflect an impairment in retrieval processes depending on executive functions
      controlled by the subcortical structures.

PMID- 7588170
TI  - [Childhood psychoses and organic pathology: results of a study of 144 cases].
AB  - The records of 144 patients of Child Psychiatry Units of Alsace (France), with
      childhood psychosis (CP) or pervasive developmental disorders (PDD) have been
      systematically screened for previous or associated pathological events. Half of
      the children studied have been or are still affected by severe somatic disorders,
      but none of the diagnostic subcategories (referring to DSM III or CFTMEA)
      appeared significantly more frequently affected. In our population, the severity
      of organic disorders was positively correlated with: the age of the mother: more
      severe cases were reported when the mother was younger than 20 or older than 40
      at the moment of childbirth; pathological events during pregnancy; early mother
      child separation during the first year of life. The most frequent associated
      disorders however (neonatal pathology 45% of the cases, epilepsy 17% of the
      cases, neurological or neurosensorial pathology 15% of the cases) were associated
      neither with a specific diagnostic nor with a clinical and social specific
      pattern. The only statistically significant correlation was found between
      neurological pathology and a relatively low level of cognitive and social
      functioning. All these results were confirmed by multivariate statistical
      analysis. A main component analysis integrating all quantified data concerning
      organic pathology was performed: it emphasizes the independence of the different
      pathological events reported. The factorial analysis including the clinical,
      diagnostical and somatic event-related data failed to show any statistical
      profile associating functional features of the children with any particular
      previous or existing somatic disorders. Our results suggest that a history of
      organic pathological events is frequent not only in autistic disorders but in any
      kind of PDD or early CP - associated with moderate to severe mental retardation,
      in most cases of our study. However, this does not demonstrate that this type of
      pathological events constitute the direct and unique cause of PDD and CP: the
      concept of the aetiology of these severe diseases must take account of other
      factors - such as relational disruption -, also frequently seen in these
      children.

PMID- 7588168
TI  - [Cognition disorders in HIV infection. Validation of a brief neuropsychological
      evaluation battery].
AB  - The objective of our study was the elaboration and the validation of a brief
      neuropsychological battery sensitive to the main cognitive and psychomotor
      deficits in HIV+ patients with HIV encephalopathy and cognitive impairment
      associated with seropositivity. We evaluated the sensitivity of this brief
      battery with respect to a large neuropsychological battery of standardized tests.
      METHODOLOGY: A brief battery (BB) (30 mn, with simple and portable material) of 5
      standardized subtests and 7 new elaborated tests and a large battery (LB) (2 h to
      2 h 30) of 16 standardized subtests, were constituted. Both screened 6 major
      cognitive areas (attention, memory, visuospatial function, psychomotor speed,
      motor dexterity, language). On the LB, subjects' age and educational level were
      considered while appraising performances to determine whether subjects had normal
      cognitive status (less than 4 abnormal test scores), borderline cognitive
      impairment (4 or 5 abnormal test scores); on the BB norms for the new tests were
      generated from the results of 24 HIV+ subjects with normal cognitive status on
      the LB and 15 HIV- subjects of a control group; performance on the BB was
      considered normal if less than 3 test scores were abnormal, or impaired if more
      than 3 test scores were abnormal. Conclusions deduced from the assessments with
      BB were compared to those obtained from LB. For all subjects, a possible anxio
      depressive component was evaluated on the basis of DSM III-R criteria and
      clinical scales (MADRS and STAXI). Subjects were included in the study
      notwithstanding mode of contamination and stage of illness and anxiodepressive
      antecedents; patients with identified brain disease or evolutive non neurological
      pathology were not included. 102 evaluations were performed on a population of
      HIV+ patients comprising 89 men and 13 women: 19 CDC II, 35 CDC III or IV C 2 and
      48 CDC IV; 76 homosexuals, 8 heterosexuals, 16 drug users and 2 transfused.
      RESULTS: the BB led to the same conclusions for 90.6% of the 53 impaired cases
      (on LB) and for 96% of the 24 normal cases. The reliability of the BB is
      therefore of 92%; there was only 1 false positive (less than 2%) and less than
      6.5% false negatives. Among the 25 subjects with borderline cognitive impairment,
      half were impaired and half were normal on the BB; most (84%) presented with
      anxio-depressive symptoms. COMMENTS AND CONCLUSION: The brief battery (BB)
      testing 6 cognitive functions could be considered as a sensitive, practical
      instrument for rapid detection of cognitive impairment in HIV+ patients, with a
      few rate of false positive or negative diagnosis. However, it is not adequate for
      determining whether psychiatric or/and organic brain pathology is at the origin
      of the deficit. Evaluation and follow-up of a possible anxio-depressive component
      has to be considered together before concluding.

PMID- 7588171
TI  - Fluvoxamine and clomipramine in depressed hospitalised patients: results from a
      randomised, double-blind study.
AB  - The efficacy of the selective serotonin reuptake inhibitors (SSRIs) and the
      tricyclic antidepressants is well established, although data on the efficacy of
      SSRIs in severe depression is limited. Several studies have demonstrated that
      fluvoxamine is as effective as clomipramine in the treatment of severe
      depression. The aim of this four-week study was to compare the efficacy and
      tolerability of fluvoxamine and clomipramine in hospitalised depressed patients.
      Patients were eligible for entry into the study if they had an established
      diagnosis of depression, and an overall score of more than 17 on the first 17
      items of the Hamilton Rating Scale for Depression (HAMD). Twenty patients
      received fluvoxamine 100-300 mg in divided daily doses (mean daily dose 204 mg),
      and 20 received clomipramine 50-150 mg in divided daily doses (mean daily dose
      106 mg) for four weeks. Efficacy was assessed using the HAMD and Clinical Global
      Impression (CGI) scales, at baseline and weekly intervals thereafter. The
      investigator's overall rating of efficacy and tolerability was also noted. At the
      end of the study, both fluvoxamine and clomipramine produced a marked to moderate
      therapeutic effect. Compared with baseline both fluvoxamine and clomipramine
      produced similar improvements in the HAMD total, HAMD item and CGI scores. More
      patients in the clomipramine group experienced anticholinergic side-effects and
      orthostatic hypotension. Furthermore, a significant difference in favour of
      fluvoxamine was found with regard to the investigator's overall assessment of
      undesirable signs and symptoms (p = 0.023; Wilcoxon's test). In conclusion,
      fluvoxamine is as effective as clomipramine in hospitalised depressed patients,
      and is better tolerated.

PMID- 7588172
TI  - [Duration of treatment for depression. IVth Marseille colloquium. Marseille,
      France, 28-29 January 1994].

PMID- 7588173
TI  - [Biological factors and resistance to antidepressive agents].
AB  - Concerning depressive disorders, biological factors remain relatively unknown.
      However, they might first be risk factors for depressive disorders and secondly
      could decrease the response to antidepressants. We studied hypothyroidism,
      diabetes and hypothalamic-pituitary-adrenal axis disorders. In terms of
      neurotransmitters, beta-adrenergic dysfunction may be involved in hypothyroidism
      and diabetes whereas a serotonergic dysfunction may be involved in hypothalamic
      pituitary-adrenal axis disorders.

PMID- 7588174
TI  - [Practical considerations in initial treatment].
AB  - The initial treatment for a depressive episode corresponds to the early period of
      treatment for depression--the period which precedes what is called the phase of
      consolidatory treatment, which itself is eventually followed by maintenance
      treatment. Its precise adjustment has been the object of many pharmacological
      studies, but nevertheless remains largely empirical. The choice of an
      antidepressant depends on the therapeutic response obtained during previous
      episodes. The choice of dosage, on the other hand, is well standardised. The
      essential element is to oversee the treatment, both to detect and correct
      undesirable effects as well as to improve the target symptoms. Certain
      therapeutic considerations must be put into practice according to the types of
      depressive swings, such as secondary depression, chronic depression, manic
      depression, and atypical depressions. In any event the initial treatment of all
      depressions remains largely empirical at the present time, and depends on
      knowledge of the management of antidepressant substances, particularly since the
      appearance of new families of MAOIs and 5HT agonists.

PMID- 7588175
TI  - [Delay of the antidepressant effect: clinical studies].
AB  - The first controlled trials of antidepressants show up a delay of antidepressant
      effect to one or two weeks, with sedative or stimulant early effects. More
      recently, several controlled trials founded on more stringent criterions (DSM
      III, period of pre-therapeutic placebo of one minimal week, frequent quotations
      etc.) have showed up a delay of antidepressant effect assigned between the fourth
      and the sixth week, with all antidepressant drugs. Nevertheless, there are more
      early effects, either specific antidepressant but incomplete either non specific
      (sedative, stimulant). These early effects are more marked with the
      antidepressant drug than with the PBO, but they have not a predictive value of
      terminal response. Several factors have an influence on the delay of
      antidepressant effect. The clinical characteristics are not correlated with this
      delay. The intravenous administration does not reduce the length of this delay.
      The pulse loading doses with intravenous and oral antidepressant drug seem to
      reduce the length of this delay. The most important factor is the placebo effect
      (Quitkin et al.). Nevertheless, the differences of efficacy between
      antidepressant and PBO appear only towards the third week. There are some
      differences during the first two weeks. In fact the PBO effect is early and late
      longer than the antidepressant drug. With PBO, when the improvement is
      progressive and fasting, it is a spontaneous remission. These data have practical
      implications if we must know the delay of antidepressant drug.

PMID- 7588178
TI  - [Consolidation treatment. The status in dysthymia].
AB  - It is now recognised that the treatment of depressive episodes comprises three
      distinct phases: the phase of acute treatment, which should lead to symptomatic
      remission; the phase of continuation, which aims to obtain cure by preventing
      relapses; and the phase of maintenance or prophylactic treatment, the object of
      which is to prevent recurrence, that is to say the occurrence of a new depressive
      episode independent of the earlier one. The application of such a therapeutic
      protocol to mood alterations raises a number of questions. In the first place, it
      should be emphasised that the fluctuating character and low intensity of the mood
      changing symptoms, as well as the normally progressive action of antidepressants
      over time may make it very difficult to date the onset of remission. For this
      reason, the phases of acute treatment and of consolidation may not be discernible
      for a certain period of time. Furthermore, the chronicity of time-course being
      one of the principal characteristics of dysthymias, the only effective long-term
      therapeutic strategy may be to pursue continuation treatment instead of
      maintenance treatment, on the grounds that every new symptomatic manifestation
      should be regarded as a relapse rather than a recurrence. The duration of
      continuation treatment is poorly defined. If credence is lent to the rule which
      states that a depressive state should be treated for as long as the prior history
      has lasted, consolidation treatment of dysthymias should be continued for several
      years--two at least, more frequently more, and sometimes indefinitely.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7588177
TI  - [Long-term clinical effects of antidepressive agents].
AB  - According to long term studies with antidepressants versus placebo, the
      therapeutic efficacy is prolonged: a long term treatment in full dosage seems to
      reduce from almost half the risk of relapse and recurrence till five years,
      during recurrent major affective disorders. We should therefore be cautious and
      we should not have a systematic prescription for all types of depressions;
      antidepressants are efficacious but have side effects and we do not know well
      their abilities in long term use. During bipolar disorders the prescription of
      long term antidepressants, even in association with normothymics, does not give
      benefits and can induce rapid cycles. In dysthymias and depressions with
      personality disorders, a psychotherapy is indicated, and it is difficult to
      evaluate the efficacy of a long term antidepressant treatment. Tricyclics
      antidepressants, MAOI's and SSRI's have classical side effects, and they can also
      induce: modifications of the symptomatology, of cognitive functions, of sleep,
      eating and sexual behaviours; modifications of the course of depressive illness,
      induction of manic switches, and may be sometimes an exacerbation of suicidal
      ideation ... pharmacogenetic modifications with their action on hepatic
      metabolism, neuroendocrine alterations and long term effects on monoamines. We
      have also to take into account the long term treatment consequences on quality of
      life, on self esteem with the importance of psychodynamic and relationships
      modifications. The use of a long term antidepressant treatment should be adapted
      to each individual, being cautious of its potential benefits and risks.

PMID- 7588179
TI  - [Practical modalities of consolidation treatment].
AB  - Long-term treatment has the double objective of consolidating the beneficial
      therapeutic effect of the initial treatment and of preventing the aggravations
      which usually occur within 6 or 8 months following the beginning of a depressive
      episode. The practical measures in long-term treatment of a depressive state are
      fairly well laid down. Effective antidepressant treatment for an isolated acute
      depressive episode should be prolonged, at the same dose, for 4 to 6 months
      following relief from the episode. Epidemiological studies confirm the
      superiority of antidepressant treatment over placebo in the prevention of
      recurrence of depressive episodes, complementing a psychotherapeutic approach.
      Treatment should always be stopped very gradually. If further recurrence occurs,
      it becomes necessary to continue treatment beyond the 6th month.

PMID- 7588176
TI  - [Spontaneous course of depression].
AB  - The study of the spontaneous course of depressions nowadays comes up against a
      number of obstacles. The most important of these is the necessity of using
      untreated cases, which virtually forces the contemporary researcher to refer to
      studies performed in the pretherapeutic era, if conclusions are not be drawn only
      from classical descriptions. Unfortunately, these studies are marked by the
      absence of strict diagnostic criteria, the heterogeneity of patients included in
      them, the lack of preciseness of evaluations and the primitive statistical
      methods used. They are concerned essentially with the duration of depressive
      phases and the factors which influence it. Among these latter are regularly found
      age, sex, the number of episodes, the duration of the preceding symptom-free
      interval, the severity and semiology of the attack, heredity, mode of onset,
      level of intelligence, the presence or absence of associated pathology and the
      presence or absence of hospitalisation. Chronicization of depression and the
      factors concerned with it have also been the object of several studies. A small
      number of investigations compare the course of the illness in untreated
      populations. The study of the spontaneous course of depression evidences the
      necessity of having consensus definitions, and may serve as a basis for a better
      comprehension of the process of cure and of the real impact of therapies designed
      to treat depression.

PMID- 7588180
TI  - [Pathologic personality, temperament and treatment].
AB  - The relationships between affective disorders and personality disorders remain
      controversial. The inefficacy of therapeutics in depressed subjects with a
      personality disorder is often due to an inadequate therapeutic. A few clinical
      arguments and experimental data corroborate the hypothesis of a commun substratum
      for affective disorders and personality disorders. A few studies demonstrate an
      efficacy in specific cases of lithium, neuroleptics and antidepressants
      (particularly MAOI) in borderline subjects with an affective disorder. We may too
      use pragmatic psychotherapies targeted on specific problems of each patient.

PMID- 7588181
TI  - [The long-term course of depression (epidemiology and clinical aspects)].
AB  - Depression recurs in three quarters of cases; it is therefore necessary to
      undertake long-term studies in order to understand the clinical and
      epidemiological implications. Current classifications schematically distinguish
      depressive episodes according to their more or less permanent and complete
      semiological expression (at least five symptoms over at least two weeks for a
      major depressive episode, versus at least two criteria for the greater part of
      the time over at least two years) or their time-scale (isolated or recurrent
      episodes; recurrent brief depressive episodes...). The terminology of therapeutic
      strategies is based on the temporal definitions of the depressive process. Thus
      one speaks of curative treatment during the acute phase of the illness (two
      months), maintenance treatment during recurrence (four to six months), and
      prophylaxis against later possible recurrences (more than six months).
      Epidemiological findings emphasize the importance not only of recurrence of
      depression (50% in the year following an index episode), but also that of
      becoming chronic (20%), of partial remissions (15 to 20%), and the
      "bipolarisation" of a unipolar illness (10 to 15%). Finally, certain risk factors
      for recurrence have been identified. The most important of these is a large
      number of previous depressive episodes.

PMID- 7588182
TI  - [Efficacy of antidepressants and thymoregulators in the long-term evolution of
      depression].
AB  - Official recommendations pointed out the long term maintenance treatment of
      recurrent unipolar depression on the basis of a significant effect of
      antidepressants and mood-stabilizers versus placebo. The results of controlled
      studies, mainly using imipramine or lithium salts, have not been encouraging in
      term of long term prognosis, due to the limited success rate for maintenance
      phase ranging from 30 to 48%. The "Pittsburgh study" maximized the recurrence
      potential by defining patients selection on at least 3 previous episodes of
      unipolar depression, with the immediate previous episode being no more than 2.5
      years earlier, beginning the experimental maintenance therapy phase after
      patients remain relatively symptom free for a total of 20 weeks, and scheduled
      the imipramine withdrawal in the randomly assigned placebo group by a progressive
      reduction of 33% per week. Survival analysis in the 5 years maintenance outcome
      of previously imipramine responders patients demonstrated an increased risk of
      depressive recurrence at the beginning of discontinuation but did not prove a
      true prophylactic effect. Furthermore these findings do not prove that treatment
      are not more effective than placebo, suggesting at least a revisitation of the
      clinical concept of response. The putative efficacy of biological treatment
      should be an operational criteria to elicit vulnerability markers, mainly in the
      field of sleep research.

PMID- 7588183
TI  - [Initiating thymoregulator treatment].
AB  - It is currently agreed that starting a lithium therapy is justified, as soon as
      the evolution of recurrent affective disorder is evident, by: the occurrence of
      an acute depressive episode during the four years preceding the current acute
      episode, that is to say 2 obvious acute episodes within 5 years which is enough
      to make highly probable a new acute short or medium dated episode; an acute manic
      episode caused by the high level of recurrence in bipolar patients and the
      frequent severe congruencies of an acute manic episode. The prophylactic efficacy
      of the lithium salts has been proved by several placebo-controlled studies: the
      result of these trials states that with placebo the recurrence level varies
      between 38% and 93%, whereas with lithium it is between 0% and 44%. The
      controlled trials in the sixties and seventies have made evident that about 1/3
      of bipolar patients do not respond to lithium, the results varying according to
      the selection tests, the duration of the observation, the definition of the
      failure. We'll address three up to date questions. 1) Whereas the level of the
      lithium therapy is rather well established (0.6 to 1 mEq/l) and is of a great
      preventive efficacy with patients that are maintained in the high zone of the
      therapy scale, the present question is to know if it is necessary to split up the
      dose of lithium or to administer the daily dose in a single dose in the
      evening.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588184
TI  - [Delay in the effect of antidepressive agents: pharmacologic approach].
AB  - A paradox which is not resolved in the use of antidepressants (ATD) is that in
      pharmacological studies of animal models of depression and in neurochemical
      studies, the onset of activity of all drugs is extremely rapid, whereas in human
      clinical practice the onset is delayed (15 days). An attempt is made to explain
      this in 3 ways, involving the synapse, transduction mechanisms, and cognition.
      Analysis of the impact of all ATDs shows that we are confronted with slow
      adaptive processes which are correlated with the delay observed in clinical
      practice. The interest of such considerations is that they may give rise to
      alternative therapies which are able not only to accelerate response, but also to
      increase it.

PMID- 7588185
TI  - Nonemergent hypertension. New perspectives for the emergency medicine physician.
AB  - The emergency medicine physician must evaluate and treat hypertensive patients in
      a variety of contexts, ranging from the compliant patient with well-controlled
      blood pressure who presents for an unrelated problem, to the patient with
      asymptomatic blood pressure elevation, to the patient with a true hypertensive
      urgency or emergency. Recently, the approach to the treatment of adult
      hypertension has been modified to take into account advances in the understanding
      of individual patient risk factors and relative risk of cardiovascular
      complications. Additionally, no data currently exist that show a benefit to
      acutely lowering the blood pressure of asymptomatic patients with severe blood
      pressure elevation, but there is data to suggest that it may be harmful,
      especially in patients with cardiovascular risk factors. From this perspective,
      the authors define hypertensive urgency and make recommendations for more careful
      deliberation in management decisions. This article, along with the article on
      hypertensive emergencies in this issue, provides an approach to the patient
      presenting to the emergency department with hypertension, elevated blood
      pressure, or both.

PMID- 7588186
TI  - Advances in the use of ancillary diagnostic testing in the emergency department
      evaluation of chest pain.
AB  - This article discusses the advances of ancillary studies used to evaluate the
      emergency department patient with chest pain caused by acute myocardial
      infarction (AMI) or ischemia. This article examines how these studies have
      improved the early detection of patients with AMI, improved differentiation of
      acute ischemic coronary events from nonischemic causes of chest pain, more
      accurately stratified patients for adverse outcome, and decreased the number of
      patients with AMI inadvertently discharged from the emergency department.
      Ancillary studies discussed include nonstandard ECGs, nuclear imaging, serum
      markers, and emergency department observation units. Emergency department
      echocardiography is discussed elsewhere in the issue.

PMID- 7588187
TI  - Thrombolytic therapy.
AB  - If the electrocardiogram is diagnostic of acute myocardial infarction (AMI) in
      the patient complaining of typical chest pain, then indications and
      contraindications for thrombolytic therapy must be assessed immediately. The goal
      is to administer a thrombolytic agent within 30 to 60 minutes of presentation to
      the emergency department. Whether or not thrombolytic therapy is administered,
      other standard therapies for AMI must not be neglected. In addition, the medical
      record would reflect the clinical decision-making process and consultation with
      an admitting physician(s).

PMID- 7588188
TI  - Acute myocardial infarction.
AB  - Because of advances in reperfusion therapy and improved outcomes through the use
      of treatment adjuncts, the morbidity and mortality from AMI have been
      significantly reduced in the past decade. Reperfusion therapy is now the standard
      of care for all patients who meet eligibility criteria. Equally important in the
      treatment of AMI, however, are the many treatment adjuncts that are universally
      available (Table 1). Aspirin and beta-blockers should be used in all patients
      without contraindications. Heparin, in turn, has a clear role in many but not all
      patients. Finally, the best application of magnesium has yet to be determined.

PMID- 7588189
TI  - Cardiotoxic drugs.
AB  - This article describes the cardiovascular effects and treatment of patients who
      have used cardiotoxic drugs. The discussion includes cocaine, methamphetamine,
      cyclic antidepressants, calcium channel blockers, beta-blockers, and digoxin. The
      authors review treatment controversies and emphasize the acute aspects of
      toxicity commonly seen in the emergency department.

PMID- 7588191
TI  - Cardiopulmonary resuscitation.
AB  - Research into the physiologic changes that occur during cardiac arrest and
      resuscitation have led to important changes in our approach to resuscitation of
      the cardiac arrest victim. Methods that improve coronary perfusion pressure,
      coupled with direct or indirect measures of coronary perfusion, are actively
      being sought to improve resuscitation rates and outcomes. These studies have
      broadened the therapeutic options available to clinicians treating the cardiac
      arrest victim. Although significant improvements in hospital discharge rates and
      neurologic outcome have not been realized as yet, a firm basis for future studies
      has been established. Overall, the most significant intervention that the
      clinician can presently perform is early and prompt defibrillation of the patient
      in ventricular fibrillation.

PMID- 7588192
TI  - Emergency medicine applications of echocardiography.
AB  - Echocardiography represents an important, accessible tool in the evaluation of
      the critically ill emergency department patient. Echocardiography provides
      anatomic and physiologic information about the cardiovascular system safely and
      at the bedside. This modality may permit early and more accurate diagnosis and
      management of a wide range of disease processes while avoiding the risks and
      costs associated with other diagnostic strategies. It is imperative that
      emergency department physicians have a working understanding of the applications
      and limitations of echocardiography to make best use of its considerable patient
      care potential.

PMID- 7588193
TI  - Cardiovascular radiography.
AB  - The differential diagnosis of acute chest pain and shortness of breath is
      extensive. A plain chest radiograph often is ordered to aid in establishing the
      precise diagnosis. Frequently, this useful imaging tool is viewed quickly, and
      thus, many important diagnostic clues can be missed. This article provides an
      organized approach to interpreting the chest radiograph and reviews some of the
      important radiographic findings of various diseases.

PMID- 7588190
TI  - Cardiovascular shock.
AB  - Few presentations to the emergency department are as critical or dramatic as the
      patient in shock. Cardiovascular disasters that commonly present with shock
      include massive pulmonary embolism, cardiac tamponade, aortic dissection and
      aneurysm, and cardiogenic shock associated with acute myocardial infarction.
      Because patients in "cardiovascular shock" have similar clinical presentations
      and a high degree of morbidity and mortality, they demand rapid, efficient, and
      aggressive evaluation and treatment. This article reviews the evaluation and
      treatment of patients presenting with cardiovascular shock.

PMID- 7588195
TI  - Wide complex tachycardia.
AB  - Wide complex tachycardias present diagnostic challenges for emergency physicians.
      The history, physical examination, and ECG provide information required to arrive
      at the correct diagnosis. When a previous history of heart disease exists, VT
      should be suspected; however, no single clinical feature is sufficiently reliable
      for distinguishing VT from SVT. Patients with VT may tolerate their dysrhythmias
      for several hours and maintain hemodynamic stability. ECG analysis is the most
      useful process in differentiating SVT and VT. Characteristics suggestive of VT
      include evidence of AV dissociation, QRS duration of longer than 0.16 seconds,
      and QRS axis between -90 degrees +/- 180 degrees. Predictive QRS morphologic
      criteria also have been established for VT. A four-step approach to ECG analysis
      has been reported to accurately identify patients with VT, but prospective
      validation in an ED setting is lacking. The initial approach to treating patients
      with wide QRS tachycardias depends on hemodynamic stability. Until the identify
      of a dysrhythmia is certain, consider all patients to be suffering from VT.
      Unstable patients require immediate cardioversion. Acute treatment of stable
      patients includes lidocaine or procainamide. Adenosine is appropriate when wide
      QRS SVT is the diagnosis, and it also has been used as a diagnostic aid to
      identify dysrhythmias. Reports of complications with the use of adenosine as a
      diagnostic agent have not yet appeared but may occur after sufficient numbers of
      cases have accumulated. Magnesium sulfate may be useful in refractory cases of VT
      and torsades de pointes. Chronic treatment of patients prone to VT may include
      complex pharmacotherapy and AICDs. Development of new class III agents and
      enhancement of AICD technology may result in improved patient outcomes and the
      availability of more choices for emergent therapy of wide QRS tachycardias.

PMID- 7588194
TI  - Cardiac and mediastinal trauma.
AB  - Injuries to the heart and mediastinal vessels comprise one of the leading causes
      of traumatic death. Although the presumed overall mortality rate of critical
      cardiac injury is very high, the survival rate of patients with cardiac trauma
      who arrive in the ED with vital signs has been reported to be significant,
      especially with penetrating as opposed to blunt chest trauma. Patients with
      lethal injury to the heart and great vessels may present with deceptively few
      signs or symptoms. The survival of these patients is entirely dependent on the
      ability of the emergency physician to make the correct diagnosis and expedite
      definitive surgical treatment. Thus, it is prudent for emergency physicians to
      maintain a high index of suspicion for these injuries in caring for patients with
      trauma to the chest. Other injuries, such as esophageal, diaphragmatic, tracheal,
      and bronchial wounds must also be considered.

PMID- 7588196
TI  - Narrow complex tachycardias.
AB  - Narrow complex tachycardias are those cardiac rhythms with a ventricular rate of
      more than 100 beats per minute and a QRS complex width of less than 0.12 seconds.
      They originate either from the SA node, from atrial tissue itself, or from in or
      around the AV node. The term SVT is generally accurate for such tachycardias. By
      diagnosing the source of an SVT and appreciating its likely cause, therapy can be
      more precisely, safely, and effectively guided to treat these patients. Atrial
      and junctional rhythms can be treated with vagal maneuvers, drugs from classes I
      to IV and other antiarrythmic agents, magnesium, and cardioversion. Some patients
      may be candidates for surgical or catheter ablation.

PMID- 7588197
TI  - Syncope in the emergency department. A cardiologist's perspective.
AB  - Syncope is a common emergency department presentation. Syncope is a benign
      condition in many cases but has a poor prognosis in a number of cardiac
      disorders. An awareness of the serious conditions that may present as syncope and
      use of a systematic approach will yield a diagnosis for most patients; however,
      some patients remain without a diagnosis. Expending large amounts of resources
      for these patients often is unnecessary.

PMID- 7588198
TI  - Hypertensive emergencies.
AB  - Hypertensive emergencies are uncommon and physiologically diverse. Consequently,
      it is difficult for most physicians to develop a familiarity with all the
      different hypertensive crises and with all drugs available for treating them
      (Table 4). Clinicians should not agonize over which is the perfect therapeutic
      agent for a particular emergency, but instead, they should focus on scrupulous
      monitoring and familiarize themselves with a few agents that will serve in most
      situations. Generally, these agents will be sodium nitroprusside and
      nitroglycerin. Vigilant neurologic monitoring is mandatory in all hypertensive
      emergencies. The early symptoms and signs of cerebral hypoperfusion can be vague
      and subtle, but if recognized, serious complications of therapy can be avoided.
      Remember, the patient may still be hypertensive. Avoid acute (during the first
      hour) reductions in MAP of more than 20% whenever possible; subsequent reductions
      should be gradual. In patients known to have markedly elevated ICP and who need
      acute reductions in their BP, serious consideration should be given to direct
      monitoring of the ICP so that CPP can be maintained within safe limits. In
      general, oral agents should not be used for the treatment of hypertensive
      emergencies. Intravenous Labetalol and intravenous nicardipine are not suitable
      for general use in hypertensive emergencies. In special situations (e.g.,
      perioperative hypertension and subarachnoid hemorrhage), however, they may be
      employed. Their role may expand with further study. Trimethaphan may be superior
      to nitroprusside for hypertension complicated by elevated ICP or cerebral
      dysfunction. Realistically, most physicians will continue to use nitroprusside.
      Intense neurologic monitoring is more important than the specific agent used.
      Nitroglycerin is the agent of choice for acute ischemic heart disease complicated
      by severe hypertension; if it fails, use nitroprusside. For aortic dissection,
      the combination of nitroprusside and IV propranolol is the therapy of choice;
      beta-blockade must be achieved rapidly or the dissection may worsen. Trimethaphan
      is also an agent for first-line therapy. Esmolol is an alternative to IV
      propranolol for the treatment of aortic dissection, if prolonged beta-blockade
      might seriously jeopardize the patient. For eclampsia, unless an expert in
      hypertension during pregnancy has established an alternative, the therapy of
      choice is hydralazine and magnesium. The treatment of subarachnoid hemorrhage is
      in flux; calcium channel blockers are used to prevent spasm, not to lower BP. If
      the BP must be lowered immediately, use nitroprusside.

PMID- 7588199
TI  - The carboxy-terminus of parathyroid hormone--inert or invaluable?

PMID- 7588201
TI  - Rapid changes in gene expression after in vivo growth hormone treatment.
AB  - GH exerts long-lasting effects on somatic growth via changes in gene expression
      and protein biosynthesis that represent the culmination of signal transduction
      pathways initiated at the cell surface. Recent studies have demonstrated that
      ligand-induced activation of the GH receptor leads to the phosphorylation of
      multiple intracellular proteins, including latent cytoplasmic transcription
      factors, Stats 1 and 3. GH treatment also has been found to induce the expression
      of several genes in both in vitro and in vivo systems, and we have shown that GH
      rapidly activates insulin-like growth factor I (IGF-I) gene transcription in
      hypophysectomized rats. In this study, using the GH-deficient, hypophysectomized
      rat as a model, we have examined the earliest changes in gene expression that
      follow a single systemic injection of GH. We find that GH induces nascent nuclear
      IGF-I transcripts within 15 min of hormone treatment, a time course that
      parallels the GH-regulated appearance of nuclear c-fos messenger RNA (mRNA). By
      contrast, nuclear transcripts for c-jun did not increase in abundance until after
      30 min after hormone injection, and the peak rise in c-jun mRNA was severalfold
      less than for c-fos or IGF-I. GH treatment also led to the acute inhibition of
      IGF binding protein-1 (IGFBP-1) and albumin gene expression. Nuclear IGFBP-1 mRNA
      levels declined to 60% of baseline at 30 min and to 30% at 60 min, in agreement
      with previous studies showing a reduction in IGFBP-1 transcription after GH.
      Nascent nuclear albumin transcripts also decreased in abundance after GH
      treatment to levels that were less than 20% of basal values at 30 and 60 min. Our
      results show that GH can acutely activate and inhibit gene expression in the
      liver. It is likely that these diverse effects of GH are mediated by multiple
      signal transduction pathways.

PMID- 7588202
TI  - Metabolism of 1 alpha-hydroxyvitamin D2 to activated dihydroxyvitamin D 2
      metabolites decreases endogenous 1 alpha, 25-dihydroxyvitamin D 3 in rats and
      monkeys.
AB  - The vitamin D analog 1 alpha-hydroxyvitamin D2 (1 alpha-OHD2) is under
      development for the treatment of secondary hyperparathyroidism and metabolic bone
      disease. This analog is metabolized in vivo to the natural active dihydroxylated
      metabolite of vitamin D2, 1 alpha,25-dihydroxyvitamin D2 [1 alpha,25-(OH)2D2]. To
      study the metabolism of this analog, an assay involving HPLC separation and
      purification of metabolites followed by RRA with the vitamin D receptor was
      developed to quantitate the active metabolites of the analog and the endogenous
      active metabolite of vitamin D3, 1 alpha,25-(OH)2D3, from the same blood sample.
      This assay was used to determine blood levels of active dihydroxylated vitamin D
      compounds in rats and monkeys treated with oral 1 alpha-OHD2. As the circulating
      1 alpha,25-(OH)2D2 level increased dose dependently in these rats and monkeys, a
      concomitant decrease in the endogenous 1 alpha,25-(OH)2D3 was observed. In rats
      orally administered more than 2.5 micrograms 1 alpha-OHD2/kg.day, a second active
      metabolite of 1 alpha-OHD2, 1 alpha,24-(OH)2D2, was detected in concentrations
      similar to those of 1 alpha,25-(OH)2D2. These results indicate that the
      regulatory control of endogenous vitamin D metabolism as well as analog
      metabolism must be considered when assessing the therapeutic potential of a
      vitamin D analog.

PMID- 7588200
TI  - Characterization of a novel parathyroid hormone (PTH) receptor with specificity
      for the carboxyl-terminal region of PTH-(1-84)
AB  - Carboxyl-terminal fragments of PTH (C-PTH) appear to have biological properties
      different from those mediated by the amino-terminal portions of PTH and PTH
      related peptide (PTHrP). To characterize a C-PTH receptor that may be involved in
      mediating these functions, we performed RRAs and affinity cross-linking studies
      with several clonal cell lines. Radiolabeled recombinant [Leu8,18,Tyr34]human PTH
      (1-84)[mutPTH-(1-84) and [Tyr34] human PTH-(19-84)[mutPTH-(19-84) showed little
      or no specific binding to stably expressed recombinant PTH/PTHrP receptors.
      However, high affinity binding was observed using osteoblast-like and rat
      parathyroid (PT-r3) cells. The apparent Kd values were 20-30 nM for PTH-(1-84),
      mutPTH-(1-84), and mutPTH-(19-84), respectively; 400-800 nM for PTH-(39-84); and
      more than 5000 nM for PTH-(53-84). [Nle8,18,Tyr34]bovine PTH-(1-34)amide [PTH-(1
      34)], PTH-(44-68), PTHrP-(37-74), and PTHrP-(109-141) showed no displacement of
      either radioligand. C-PTH receptor number was increased up to 2-fold by
      pretreating ROS 17/2.8 cells with increasing doses of PTH-(1-34), PTH-(1-84), or
      8-bromo-cAMP, whereas no change was observed in response to dexamethasone or PTH
      (39-84). Cross-linking studies using radiolabeled mutPTH-(1-84) or mutPTH-(19-84)
      revealed specific labeling of two proteins in ROS 17/2.8 cells that were
      approximately 40 and 90 kilodaltons in size (including the radioligand of
      approximately 10 kilodaltons). The intensity of affinity labeling of both
      proteins was dose dependently inhibited by increasing concentrations of unlabeled
      PTH-(1-84) and several carboxyl-terminal PTH-(1-84) fragments, but not by PTH-(1
      34). Similar studies with PT-r3 cells revealed only a single protein band of
      about 90 kilodaltons. These data indicate that the carboxyl-terminal portion of
      PTH-(1-84) binds specifically to a unique receptor/binding protein distinct from
      the previously isolated PTH/PTHrP receptor.

PMID- 7588204
TI  - Luteinization in primates is accompanied by loss of a 43-kilodalton adenosine
      3',5'-monophosphate response element-binding protein isoform.
AB  - Although granulosa cell differentiation and corpus luteum function are both
      regulated by cAMP, there are development-dependent differences, particularly at
      the level of gene expression and cell proliferation, between the responses of
      follicular granulosa cells and luteal cells to trophic hormone stimulation. In
      this study, we sought to determine whether these differences could be due to
      changes in the cellular expression of cAMP response element (CRE)-binding protein
      (CREB). Immunocytochemical analysis of macaque ovaries revealed a development
      related alteration in the subcellular distribution of CREB-immunoreactive
      material. Immunoreactive CREB was present in nuclei of follicular granulosa cells
      from maturing follicles, whereas after ovulation and luteinization, no CREB
      immunoreactive proteins were visualized in luteal cell nuclei. Anti-CREB
      immunoblotting of granulosa cell extracts from macaque preovulatory follicles as
      well as extracts of granulosa cells from luteinizing human follicles revealed a
      43-kilodalton (kDa) protein, a size typical of native CREB. In contrast, whole
      cell extracts of monkey corpora lutea collected during the early, mid-, and late
      luteal phases completely lacked a 43-kDa CREB signal. The absence of 43-kDa CREB
      isoforms in corpora lutea was confirmed using three different antisera directed
      against different regions of CREB. Using a human collagenase gene CRE to probe
      Southwestern blots, a 43-kDa CREB was observed in follicular cell extracts,
      whereas no CRE-binding activity was found in corpora lutea extracts using this
      probe. We also sought to determine whether the loss of expression of the 43-kDa
      CREB isoform may be functionally correlated with the cessation of cellular
      proliferation that accompanies luteinization. Expression of proliferating cell
      nuclear antigen (PCNA), an obligatory component of DNA polymerase delta, is
      essential for proliferation and has been shown by others to be CRE dependent.
      Immunoblotting of follicle cell and luteal cell extracts with an anti-PCNA
      monoclonal antibody revealed PCNA expression in granulosa cells and no detectable
      PCNA expression in corpora lutea. These findings indicate that as follicular
      granulosa cells progress from the proliferative state to terminally
      differentiated luteal cells, there is a cessation of expression of a 43-kDa
      member of the CREB family of transcription factors, and there may be an
      association between the loss of CREB isoforms and cessation of PCNA expression.

PMID- 7588203
TI  - 11 beta-hydroxysteroid dehydrogenase is an exclusive 11 beta- reductase in
      primary cultures of rat hepatocytes: effect of physicochemical and hormonal
      manipulations.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the conversion of
      corticosterone to inert 11-dehydrocorticosterone, thus regulating glucocorticoid
      access to intracellular receptors. This type 1 isoform (11 beta HSD-1) is a
      bidirectional NADPH(H)-dependent enzyme in vitro and is highly expressed in
      liver, where it is regulated by glucocorticoids, thyroid hormones, estrogen, and
      GH in vivo. In humans in vivo, enzyme inhibition alters glucose homeostasis, an
      effect thought to be mediated in the liver. However, detailed investigation of
      the biology of 11 beta HSD-1 in liver, its function, regulation, and indeed even
      reaction direction, has been hampered by the lack of clonal hepatic cell lines
      that express 11 beta HSR-1. Studies of nonhepatic cell lines have suggested that
      11 beta HSD-1 is directly regulated by hormones, and transfection of nonhepatic
      cell lines has sown that reaction direction varies between cell types, possibly
      reflecting intracellular cosubstrate (NADP+/NADPH) ratios or PH. To investigate
      reaction direction and gene regulation of 11 beta HSD-1 in hepatocytes, we
      defined conditions for primary culture of adult rat hepatocytes that maintain
      high 11 beta HSR-1 messenger RNA expression. In intact primary hepatocytes over a
      wide range of steroid concentrations (2.5-250 nM), 11 beta-reduction was the
      predominant reaction direction [33.5 +/- 0.5% conversion of 11
      dehydrocorticosterone (25 nM) to corticosterone after 30 min], with undetectable
      11 beta-dehydrogenation. However, homogenates of hepatocyte cultures showed
      plentiful 11 beta-dehydrogenase activity. Treatment of hepatocyte cultures with
      the metabolic inhibitors sodium azide (5 nM) and KCN (1 nM) altered cellular
      NADP+/NADPH ratios from 0.244 +/- 0.042 in controls to 0.020 +/- 0.001 and 0.152
      +/- 0.009, respectively, but had no effect on 11 beta-reductase or 11 beta-
      dehydrogenase activity. High concentrations of KCN (10 mM) modestly increased 11
      beta-reductase activity (32.4 +/- 1.7% to 48.8 +/- 0.5%, whereas 11 beta
      dehydrogenation remained at the limit of detection. Manipulation of culture
      medium pH (6.2-8.0) had no effect on enzyme activity. Dexamethasone (10-7 M)
      induced hepatocyte 11 beta-reductase activity from 23.4 +/- 0.7% to only weakly
      affects reaction direction. Glucocorticoid and insulin regulation of hepatic 11
      beta HSD-1 is directly mediated, but other hormonal controls are either lost in
      culture or mediated indirectly. This primary hepatocyte culture system will allow
      investigation of the control of 11 beta-reductase activity and its implications
      for glucocorticoid-regulated hepatic functions.

PMID- 7588208
TI  - Interleukin-1 beta-induced nitric oxide synthase expression by rat pancreatic
      beta-cells: evidence for the involvement of nuclear factor kappa B in the
      signaling mechanism.
AB  - Recent evidence indicates that overproduction of nitric oxide mediates cytokine
      induced inhibition of insulin secretion by pancreatic islets. The current studies
      were designed to characterize signaling events involving the transcriptional
      factor NFkappaB in interleukin-1 (IL-1)-induced expression of inducible nitric
      oxide synthase (iNOS) by primary and transformed rat pancreatic beta-cells. Due
      to limitations of cell numbers of purified primary beta-cells, biochemical and
      molecular studies were performed primarily using the insulinoma cell line,
      RINm5F. Inhibitors of NFkappaB, diethyldithiocarbamate, pyrrolidine
      dithiocarbamate, and N-acetyl cysteine prevent IL-1-induced iNOS expression at
      the level of messenger RNA, protein, and nitrite generation. IL-1 induces a time
      dependent translocation of NFkappaB from cytosol to nucleus, with maximal
      translocation observed approximately 15-30 min after IL-1 treatment, as
      determined by electrophoretic mobility shift assays. The specificity of the band
      containing the NF kappa B DNA-protein complex was shown by competition with a 150
      fold excess of nonradiolabeled NF kappa B oligonucleotide. Supershift assays
      using immunoglobulins G against NF kappa b subunits p50 an p65 indicate that the
      protein complex contains a heterodimer of p50 and p65. IL-1-induced translocation
      of NF kappa B was blocked by 100 microns 100 microM diethyldithiocarbamate or 100
      microM pyrrolidine dithiocarbamate, further establishing a critical role for NF
      kappa B in the induction of iNOS by IL-1 in rat pancreatic beta-cells. Activation
      of tyrosine kinase appears to precede NF kappa B activation, as the tyrosine
      kinase inhibitor genistein (100 microM) blocks IL-1-induced translocation of NF
      kappa B. An understanding of the signal transduction pathway of cytokine-induced
      nitric oxide generation by beta-cells will provide strategies of intervention to
      further evaluate the role of nitric oxide in mediating beta-cell dysfunction.

PMID- 7588206
TI  - Transcriptional repression of insulin-like growth factor I by glucocorticoids in
      rat bone cells.
AB  - Insulin-like growth factor I (IGF-I) is an abundant autocrine and paracrine
      growth factor secreted by osteoblasts. It promotes osteoblast proliferation and
      expression of their differentiated phenotype. Glucocorticoids decrease IGF-I
      production by osteoblasts, which may mediate some actions of the steroid on bone
      in both normal and pathological states. The mechanisms by which the
      glucocorticoid cortisol down-regulates IGF-I transcripts were explored using
      cultures of osteoblast-enriched cells derived from fetal rat calvaria (Ob cells).
      Repression of IGF-I transcripts was apparent after 8 h of treatment, was
      sustained for at least 24 h, and was not altered by cotreatment with
      cycloheximide. Cortisol did not alter the stability of IGF-I messenger RNAs in
      transcriptionally arrested Ob cells. Cortisol decreased IGF-I heterogeneous
      nuclear RNA and gene transcription, as determined by reverse transcription-linked
      polymerase chain reaction and nuclear run-on assay, respectively. Transient
      transfection of Ob cells with constructs containing portions of the rat IGF-I
      exon 1 promoter and 5'-flanking DNA linked to the reporter gene luciferase were
      performed to determine glucocorticoid-responsive region of the rat IGF-I exon 1
      promoter was localized to 34 to 192 relative to the first start site of
      transcription. In conclusion, cortisol inhibits the transcription of IGF-I in
      osteoblasts, an effect that may be relevant to the actions of cortisol in bone.

PMID- 7588207
TI  - Regulation of glucose transporters in cultured rat adipocytes: synergistic effect
      of insulin and dexamethasone on GLUT4 gene expression through promoter
      activation.
AB  - A triggering effect of insulin on GLUT4 expression in adipocytes is consistently
      observed in vivo, whereas GLUT1 is roughly unaffected. However, in cultured rat
      adipocytes, insulin increases GLUT1 but fails to increase GLUT4, suggesting that
      additional factors are involved in vivo. This prompted us to evaluate the
      potential role of glucocorticoids as coregulators with insulin of glucose
      transporter expression using 3T3-F442A adipose cells and primary cultured rat
      adipocytes. In both systems, insulin increased and dexamethasone decreased GLUT1
      messenger RNA (mRNA) and protein, an effect inhibited by the glucocorticoid
      antagonist RU 38486. When the two hormones were added together, the effect of
      dexamethasone was dominant in 3T3-F442A cells, but was totally antagonized in rat
      adipocytes. Moreover, in rat adipocytes, the GLUT1 gene transcription rate (run
      on) was identical in the absence or presence of the two hormones. With regard to
      GLUT4 expression, neither insulin nor dexamethasone alone had any significant
      effect after 2 days of treatment. In contrast, the combined hormones markedly
      increased GLUT4 mRNA (+550% in rat adipocytes; +130% in 3T3-F442A cells) and
      protein (+164% in rat adipocytes; +79% in 3T3-F442A cells) with a 24- to 48-h
      delay after mRNA induction. Studies of the molecular mechanism(s) showed that
      exposure of rat adipocytes to dexamethasone plus insulin did not affect GLUT4
      mRNA stability, but increased the GLUT4 gene transcription rate 3-fold. Transient
      transfections of rat adipocytes with the 5'-flanking 2.2-kilobase sequence of the
      rat GLUT4 gene fused to luciferase demonstrated that promoter activity was
      unchanged by insulin, increased 50% by dexamethasone, and increased 3-fold in the
      presence of both. These data show that insulin elicits an increase in GLUT4 gene
      expression provided glucocorticoids are present. Our results indicate that the
      synergism between insulin and glucocorticoids on GLUT4 gene transcription is
      mediated through GLUT4 promoter activation.

PMID- 7588209
TI  - Dexamethasone-induced antagonism of growth hormone (GH) action by down-regulation
      of GH binding in 3T3-F442A fibroblasts.
AB  - Supraphysiological levels of glucocorticoids, whether endogenous (Cushing's
      syndrome) or exogenous (glucocorticoid therapy), inhibit growth in children and
      immature animals. This effect has long been suspected to be due to glucocorticoid
      antagonism of GH action at the level of peripheral tissues. In the present study
      we demonstrate direct antagonism of GH action at the cellular level by the
      artificial glucocorticoid dexamethasone. Dexamethasone was found to inhibit the
      ability of GH to elicit several early events in GH signaling in 3T3-F442A
      fibroblasts. Dexamethasone (100 nM) for 24 h decreases by 50-75% GH-induced
      tyrosyl phosphorylation of mitogen-activated protein kinases ERK1 and ERK2, the
      transcription factor Stat3/APRF, the GH receptor-associated tyrosine kinase JAK2,
      and the GH receptor. These effects appear to be specific to GH. Dexamethasone
      does not inhibit induction of tyrosyl phosphorylation of ERK proteins by
      epidermal growth factor or phorbol myristate acetate, nor does it block induction
      of tyrosyl phosphorylation of Stat3/APRF by leukemia inhibitory factor or
      interleukin-6, or induction of JAK2 by leukemia inhibitory factor or interferon
      gamma. Dexamethasone does not decrease the expression of ERK1 or -2, Stat3, or
      JAK2 proteins. Rather, the effects of dexamethasone on GH action appear to be due
      to a decrease in the number of GH receptors in the plasma membrane. Twenty-four
      hour treatment with dexamethasone leads to a 50% decrease i GH binding, which
      Scatchard analysis suggests is due to a decrease in GH receptor number. These
      findings suggest that glucocorticoids antagonize cellular GH action by decreasing
      GH binding, suggesting a mechanism by which systemic glucocorticoids could
      antagonize GH action in peripheral tissues.

PMID- 7588205
TI  - The follicle-stimulating hormone (FSH) beta- and common alpha-subunits are
      expressed in mouse testis, as determined in wild-type mice and those transgenic
      for the FSH beta-subunit/herpes simplex virus thymidine kinase fusion gene.
AB  - Testicular expression of the endogenous FSH beta-subunit (FSH beta) and common
      alpha-subunit (C alpha) genes, as well as a Herpes simplex virus type 1 thymidine
      kinase (tk) transgene, driven by a 2.3-kilobase fragment of the bovine GSH beta
      promoter, were studied at messenger RNA and protein level in normal and
      transgenic mice. A major 3.8-kb species of FSH beta messenger RNA was
      demonstrated i the normal mouse testis by Northern hybridization. This was longer
      than the main 1.7-kb FSH beta transcript detected in the pituitary gland. Reverse
      transcription-polymerase chain reaction, followed by Southern hybridization,
      demonstrated FSH beta and tk expression in the pituitary gland and gonads of
      adult normal and transgenic mice, respectively. The C alpha expression was
      detected by reverse transcription-polymerase chain reaction in the pituitary
      gland and testis. During development, testicular transcription of the FSH beta
      and tk genes was initiated simultaneously a few days after birth.
      Immunocytochemistry of adult testes showed stage-specific positive reaction with
      FSH beta, C alpha, and tk antisera in the pachytene spermatocytes and type B
      spermatogonia, but not in Sertoli cells. Positive reaction with these antisera
      was also seen in the interstitial tissue. These results demonstrate testicular
      expression of the endogenous FSH subunit genes and confirm that the testicular
      expression of the FSH beta /tk transgene reflects or its subunits play a
      paracrine or autocrine role in the regulation of testicular function.

PMID- 7588210
TI  - Activin causes premature superovulation.
AB  - In the rat ovary, follicle cells produce and respond to activin, but as yet, the
      functional significance of the autocrine/paracrine effects of ovarian activin
      remains equivocal. To assess the effects of activin on folliculogenesis, normal
      cycling female rats were injected once every 8 h over a 40-h period with
      recombinant human activin A (120 micrograms/kg) beginning at 1300 h on estrus
      (day 1 of treatment). A total of 10 rats were injected with activin in 2 separate
      experiments. On days 3 and 4 of treatment, blood was obtained for hormone
      measurements, and the ovaries were removed for histology. Follicle counts were
      performed in 1 ovary from 3 representative animals in each treatment group. All
      antral (Graafian) follicles 300 microns or more in diameter were measured and
      classified as healthy or atretic based on the number of pyknotic nuclei in the
      largest cross-section. On day 3, all rats were in diestrus (diestrous day 2).
      After 3 days of activin administration, serum levels of estradiol were increased
      200%, progesterone levels were decreased 67%, and FSH levels were unchanged
      compared with those in matched controls. By day 4 (i.e. 1 day after the last
      injection), no changes in the levels of these hormones were observed. Injection
      of activin for 3 days did not change the total number of antral follicles per
      ovary (control, 41.3 +/- 4.9; activin, 43.7 +/- 3.9); however, activin
      significantly increased the total number of atretic follicles (control, 69%;
      activin, 92%). Morphometric analysis of the ovaries removed on day 3 showed a
      marked increase (2-fold) in the number of large follicles, but most (89%) were
      atretic. Follicle counts suggested that the additional large follicles may have
      come from the pool of healthy small follicles. Histological studies showed that
      some of the day 3 activin-treated follicles had initiated ovulation. On day 4,
      control and activin-treated animals were at proestrus and estrus, respectively.
      Therefore, activin shortened the estrous cycle by 1 day. Little or n change in
      the follicle populations was observed in day 4 control ovaries. Interestingly,
      however, in 2 of the 3 activin-treated animals, 1 set of large follicles had
      ovulated (12 +/- 1 expanded egg cumulus complexes/oviduct), and another set (13
      +/- 2) was just about to rupture. The activin-exposed oocytes (tubal and
      follicular) appeared arrested in metaphase I. After ovulation, activin-treated
      follicles developed into typical corpora lutea. No ovulations were found in
      control animals.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588211
TI  - Catecholaminergic inhibition by hypercortisolemia in the paraventricular nucleus
      of conscious rats.
AB  - Administration of glucocorticoids decreases the release of corticotropin
      releasing hormone and in vitro turnover of norepinephrine (NE) in the
      paraventricular nucleus (PVN) of the hypothalamus, and immobilization (IMMO)
      markedly increases NE release and stimulates corticotropin-releasing hormone
      neurons in the PVN. This study assessed whether hypercortisolemia affects in vivo
      indexes of catecholaminergic activation in the PVN. Microdialysis was used to
      simultaneously measure PVN microdialysate concentrations of NE, the neuronal NE
      metabolite dihydroxyphenylglycol, the extraneuronal NE metabolite
      methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic
      acid before, during, and after 2 h of IMMO. Catecholamine synthesis was examined
      based on elevations of 3,4-dihydroxyphenylalanine levels after local perfusion
      with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. Cortisol (CORT; 25
      mg/kg.day) or vehicle (VEH; saline) was infused sc for 7 days via an osmotic
      minipump. CORT-treated rats had lower basal NE, dihydroxyphenylglycol,
      methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and
      significantly smaller levels of all these compounds during IMMO than VEH-treated
      rats. CORT-treated rats also had less NSD-1015-induced accumulation of
      microdialysate 3,4-dihydroxyphenylalanine at baseline and during IMMO than VEH
      treated rats. Basal and IMMO-induced plasma ACTH and corticosterone responses
      were reduced in CORT-treated rats. The results indicate that chronic
      hypercortisolemia decreases basal levels and stress-induced increments in indexes
      of release, metabolism, turnover, and synthesis of catecholamines in the PVN and
      suggest that glucocorticoids restrain the limit of hypothalamo-pituitary
      adrenocortical axis activation during stress by attenuating catecholamine
      synthesis and release in the PVN.

PMID- 7588212
TI  - Evidence that cellular proliferation contributes to relaxin-induced growth of
      both the vagina and the cervix in the pregnant rat.
AB  - It is well established that cervical growth during rat pregnancy is relaxin
      dependent. The first objective of this study was to determine if relaxin also
      promotes vaginal growth in the pregnant rat. Finding that this is the case, the
      second objective of this study was to determine if cell proliferation accompanies
      relaxin-dependent vaginal and cervical growth during rat pregnancy. Primiparous
      pregnant rats were ovariectomized (O) or sham ovariectomized (group C) on day 9
      (D9) of pregnancy, before relaxin (R) is detectable in the peripheral
      circulation. After ovariectomy, rats were treated continuously with progesterone
      (P) and estrogen (E, group OPE), or P, E, and porcine R (group OPER) in doses
      that restored normal pregnancy and parturition parameters. P and E were
      administered via silicon tubing implants. R was administered from miniature
      osmotic pumps. Vaginas and cervices were collected on D9 and D22 from group C,
      and on D22 from groups OPE and OPER (n = 6/group). Vaginas and cervices were
      weighed, frozen, and lyophilized until dry. Dried tissues were weighed,
      homogenized, and their DNA contents were determined. In sham-operated controls
      (group C), the wet weight, dry weight, and DNA contents of both the vagina and
      cervix increased 50-300% from D9-D22. On D22, vaginal and cervical wet and dry
      weights were significantly lower than controls in R-deficient group OPE; whereas,
      they were greater than controls in group OPER. Similarly, on D22, vaginal and
      cervical DNA content did not differ from D9 controls in group OPE; whereas they
      exceeded D22 controls in group OPER. In conclusion, this study demonstrates that
      vaginal growth during the second half of rat pregnancy is R dependent.
      Additionally, this study provides evidence that R may contribute to both vaginal
      and cervical growth by promoting cellular proliferation.

PMID- 7588213
TI  - Studies on the microheterogeneity and in vitro activity of glycosylated and
      nonglycosylated recombinant human prolactin separated using a novel purification
      process.
AB  - Recombinant human PRL was produced in a murine C127 cell expression system and
      purified to greater than 97% homogeneity using anion and cation exchange
      chromatography. This material was biologically equivalent to pituitary-derived
      PRL in both an enzyme-linked immunosorbent assay and the Nb2 lymphoma cell
      proliferation assay. The predominant PRL forms were identified by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and immunoblotting as being 23 and 25
      kilodaltons (kDa). These mass values were confirmed by electrospray mass
      spectroscopy. Glycosidase digestions indicated that the 25-kDa PRL is N
      glycosylated and sialylated, whereas 23-kDa PRL is nonglycosylated. Glycosylated
      and nonglycosylated forms of the hormone were individually purified to greater
      than 95% homogeneity using novel cation exchange chromatography. Isoelectric
      focusing demonstrated that both forms consist of multiple charge isomers, with
      the charge heterogeneity of the glycosylated form primarily due to differences in
      sialylation. Monosaccharide analysis of the glycosylated form suggested a minimal
      complex oligosaccharide chain that may be fucosylated and partially sialylated.
      Oligosaccharide mol wt were determined by electrospray ionization mass
      spectroscopy. Analysis of the oligosaccharides by fluorophore-assisted
      carbohydrate electrophoresis indicated that bi- and triantennary oligosaccharide
      forms are predominant and have multiple combinations of terminal sialylation.
      Both forms of PRL were active in the Nb2 lymphoma cell proliferation assay;
      however, the 23-kDa nonglycosylated form was 3-4 times more active in this assay
      than the 25-kDa glycosylated form.

PMID- 7588217
TI  - Effect of acetylcholine on corticotropin-releasing factor gene expression in the
      hypothalamic paraventricular nucleus of conscious rats.
AB  - To examine the physiological role of cholinergic input in the regulation of CRF
      neurons in the paraventricular nucleus (PVN) of the hypothalamus, acetylcholine
      (ACh) was microinjected bilaterally into the dorsolateral border of the PVN of
      conscious rats. Changes in the levels of POMC messenger RNA (mRNA) in the
      anterior pituitary, CRF mRNA in hypothalamic tissue containing the PVN, and
      plasma ACTH were assessed. Plasma ACTH concentrations increased in a dose
      dependent manner after ACh injection (1-100 pmol/side), reaching a peak 30 min
      after ACh injection and returning to baseline within 120 min. The POMC mRNA level
      in the anterior pituitary and the hypothalamic CRF mRNA level increased in a dose
      dependent manner 120 min after ACh (0.1-10 pmol/side) injection.
      Intracerebroventricular pretreatment with atropine completely abolished the ACh
      induced increase in plasma ACTH concentrations, whereas pretreatment with
      hexamethonium was without significant effect. The intracerebroventricular
      injection of ACh also increased plasma ACTH concentrations in a dose-dependent
      manner in conscious rats, but not in pentobarbital-anesthetized animals. Thus,
      cholinergic hypothalamic input stimulates CRF gene expression in the PVN and CRF
      secretion into the portal circulation under physiological conditions. The use of
      conscious animals is essential in elucidating the physiological roles of
      neurotransmitters and other modulators regulating CRF neurons.

PMID- 7588215
TI  - Effect of 3,5,3'-Triiodothyronine (T3) administration on dio1 gene expression and
      T3 metabolism in normal and type 1 deiodinase-deficient mice.
AB  - The type 1 deiodinase (D1) catalyzes the monodeiodination of T4 to produce T3,
      the active thyroid hormone. In the C3H mouse, hepatic D1 and the dio1 messenger
      RNA (mRNA) are only 10% that in the C57 strain, the common phenotype. Low
      activity cosegregated with a series of five GCT repeats located in the 5'
      flanking region of the C3H dio1 gene that impaired C3H promoter potency and
      provided a partial explanation for the lower D1. The present studies were
      performed to search for additional explanations for low D1 activity in C3H mice.
      Previous studies have shown that T3 up-regulates the dio1 gene. Therefore, loss
      of the capacity to respond to endogenous T3 is a possible additional cause of the
      lower D1 levels in the C3H mice. The hepatic C3H dio1 mRNA increases 10- to 20
      fold after T3 administration. The t3 effect occurs at a transplantation level and
      T3 does not alter the dio1 mRNA half-life. Despite the transcriptional response
      to T3, no functional thyroid response elements were identified in the 1.5
      kilobase 5'-flanking region of either the C57 or C3H dio1 gene. After the same
      dose of exogenous T3, both dio1 mRNA and D1 of the C3H mouse respond to a greater
      extent than those of the C57 strain. This can be explained in part by the
      reduction in T3 clearance due to the lower D1 levels in C3H mice in which higher
      concentrations of circulating T3 are maintained. The decrease in serum T3 levels
      and T3 production observed in fasting and systemic illness in both human and
      experimental animals has been attributed in part to a decrease in hepatic D1. In
      contrast, despite markedly lower hepatic and renal D1 levels, serum T3
      concentrations remain normal in C3H mice. The present studies suggest that the
      absence of stress-induced hypothalamic-pituitary suppression that allows T4
      production to be maintained together with the reduced clearance of T3 and T4 via
      inner ring deiodination compensate for the D1 deficiency.

PMID- 7588220
TI  - Effect of insulin-like growth factor I in murine muscular dystrophy.
AB  - In muscular dystrophy there is an imbalance between muscle protein synthesis and
      protein degradation, resulting in net muscle catabolism and progressive muscle
      weakness and wasting. Both insulin and insulin-like growth factor I (IGF-I) are
      known to have an anabolic effect on skeletal muscle, which is believed to be
      enhanced in the presence of elevated concentrations of amino acids. We examined
      the effects of 4-week administration of recombinant human IGF-I (rhIGF-I), both
      alone and supplemented with a high protein diet (HPD), on muscle metabolism,
      morphology, and function in the 129 ReJ dystrophic mouse. rhIGF-I significantly
      reduced muscle protein degradation (P < 0.001), increased muscle protein content
      (P < 0.05), decreased fiber area variability (P < 0.01), and increased hind limb
      utilization (P < 0.01). Supplementation of rhIGF-I therapy with a HPD resulted in
      a significant increase in muscle protein synthesis (P < 0.05) in addition to a
      further increase in the above parameters. We conclude that rhIGF-I causes an
      improvement in muscle metabolism, morphology, and function in dystrophic mice,
      and this effect is further enhanced by the presence of a HPD.

PMID- 7588216
TI  - Characterization of rat GLUT5 and functional analysis of chimeric proteins of
      GLUT1 glucose transporter and GLUT5 fructose transporter.
AB  - To investigate the biological and biochemical properties of GLUT5, rat GLUT5
      complementary DNA was transfected into Chinese hamster ovary cells. Rat GLUT5 was
      exclusively targeted to the plasma membrane and exhibited a transport activity,
      not for glucose, but for fructose. The affinity for fructose (Km = 11.6mM) was
      much higher than that of GLUT2, the other glucose transporter with fructose
      transport activity. Interestingly, rat GLUT5 was not photolabeled with 0.5 microM
      cytochalasin B, whereas a similar amount of GLUT1 was adequately photolabeled
      under the same experimental conditions. Next, to investigate the domains required
      for transport of glucose/fructose in GLUT1 and/or GLUT5, several chimeric
      GLUT1/GLUT5 proteins were expressed, and their glucose and/or fructose transport
      activities were studied. The intracellular middle loop and the region
      encompassing the membrane spanning domains 7-12 were observed to have crucial
      roles in GLUT1 glucose transport, whereas replacement of the N-terminal half or
      the intracellular C-terminal region with the corresponding region of GLUT5
      produced no marked effects on glucose transport activity. In contrast, both the N
      terminal half encompassing the region from the N-terminus through the 6th
      membrane spanning domain and the intracellular C-terminal region were mandatory
      for GLUT5 fructose transport. In conclusion, GLUT5 is a transporter exclusively
      for fructose and the structural requirements for fructose transport are more
      stringent than those for glucose transport among hexose transporter proteins.

PMID- 7588222
TI  - Sphingosine derivatives inhibit depolarization-evoked calcium entry in rat GH4C1
      cells.
AB  - Several investigations have suggested that sphingosine (SP) derivatives are
      potent inhibitors of protein kinase C. In GH4C1 cells, protein kinase C is a
      potent modulator of voltage-operated calcium channels (VOCCs). The aim of the
      present study was to investigate whether SP derivatives could modify calcium
      entry via VOCCs. Using fura-2-loaded cells and 45Ca2+ flux studies, we show that
      several SPs potently and rapidly inhibit depolarization-evoked calcium entry in a
      dose-dependent manner. The effect was not due to an enhanced efflux of calcium
      from the cells, as the depolarization-evoked entry of Ba2+ was inhibited by the
      SPs. A similar inhibition was observed with 1,2-dioctanoylglycerol, an activator
      of sphingomyelinase in GH3 cells. Phorbol myristate acetate and 1-oleyl-2
      acetylglycerol had only a modest inhibitory effect. Furthermore, whole cell patch
      clamp experiments showed that sphingosinephosphorylcholine (SPC) potently
      attenuated calcium entry via VOCCs. In experiments using cells grown on
      coverslips, we found that the inhibitory effect of SPC on calcium entry was
      reversible. The addition of sphingomyelinase or hexanoyl ceramide, a cell
      permeable ceramide, only modestly inhibited the depolarization-evoked entry of
      calcium, whereas arachidonic acid and phosphatidic acid had no effect. The SP
      metabolite sphingosine-1-phosphate had no effect on the entry of calcium. The
      results suggest that the effects of the SPs were probably not the result of a
      conversion to ceramide or of the production of other lipid second messengers. In
      cells with down-regulated protein kinase C, SPC, SP, and 1,2-dioctanoylglycerol
      inhibited depolarization-evoked calcium entry, suggesting that the inhibition was
      independent of an action mediated via protein kinase C. The SPs per se did not
      induce any changes in intracellular free calcium, and they did not inhibit the
      TRH-evoked release of sequestered calcium in the cells. However, TRH-evoked
      calcium entry was inhibited. The results suggest that SPs are potential
      regulators of calcium entry mediated by VOCCs in GH4C1 cells.

PMID- 7588221
TI  - Mechanism of androgen-induced thymolysis in rats.
AB  - To investigate the mechanism of androgen-induced thymolysis, the effects of
      various androgens, including testosterone (T), 19-nortestosterone, and 7 alpha
      methyl-19-nortestosterone (MENT), were compared with those of estradiol and
      dexamethasone (DEX) in intact, castrated, and adrenalectomized male rats. The
      potency comparisons on thymus regression, based on mass of steroids, showed DEX
      to be the most potent, followed by estradiol and the androgens. Among the
      androgens, MENT was the most potent, followed by nortestosterone and T, an order
      similar to their anabolic potency on muscle. As the thymolytic effects of T and
      MENT were not altered by the concomitant administration of an aromatase inhibitor
      or a 5-reductase inhibitor, it was concluded that the effects of androgens were
      not mediated by their conversion to estrogens or 5 alpha-reduced metabolites.
      Involvement of glucocorticoid receptors in androgen action was excluded because
      mifepristone (an antiglucocorticoid) blocked DEX-induced, but not T- or MENT
      induced, thymus regression. Flutamide, an antiandrogen, significantly blocked the
      thymolytic effect of T and MENT, providing further support for this conclusion.
      This suggested that the thymolytic action of androgens is an intrinsic property
      mediated via androgen receptors (AR). The occurrence of AR in the thymus was
      demonstrated by binding assays and the presence of AR messenger RNA (mRNA) by
      reverse transcriptase-polymerase chain reaction. Quantitative reverse
      transcriptase-polymerase chain reaction for AR mRNA in the thymus showed 6-fold
      more AR mRNA in the thymic epithelial cells than in the thymocytes. However,
      epithelial cells represent only a small fraction of the thymus. Hence, it is
      hypothesized that the androgens produce their thymolytic effects by stimulating
      the secretion of a factor(s) by the thymic epithelial cells that, in turn, causes
      regression of the thymus.

PMID- 7588218
TI  - Desensitization of gonadotropin-releasing hormone action in the gonadotrope
      derived alpha T3-1 cell line.
AB  - Sustained exposure of gonadotropes to GnRH causes a pronounced desensitization of
      GnRH-stimulated gonadotropin release, but the mechanisms involved are poorly
      understood. Recent studies have suggested, however, that GnRH-stimulated
      phosphoinositidase C (PIC) activity does not undergo rapid ( < 5 min) homologous
      desensitization in alpha T3-1 cells, and we have, therefore, used this cell line
      to address the question of whether desensitization occurs distal to PIC activity
      and/or in an intermediate time frame. We show that GnRH stimulates a rapid
      increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3; maximum at 10-20 sec with
      a modest reduction thereafter] and that the GnRH-stimulated accumulation of
      [3H]IPs (in cells stimulated in the presence of LiCl) increases linearly over 5
      300 sec. This clearly indicates that desensitization of PIC does not occur within
      this period and that the dramatic reduction in the rate of Ins(1,4,5)P3
      accumulation (10-30 sec) is due to its metabolism, rather than to a reduction in
      Ins(1,4,5)P3 generation. Pretreatment for 60 min with 10(-7)M GnRH reduced cell
      surface GnRH receptor number by 48% (without measurably altering Kd). The
      pretreatment also reduced maximal GnRH-stimulated [3H]IP accumulation (to 66% of
      the control) and increased the EC50 for GnRH-stimulated [3H]IP accumulation
      approximately 3-fold, demonstrating that desensitization of GnRH-stimulated
      [3H]IP accumulation can, indeed, occur within 60 min, but that this may be
      attributable to receptor loss (without appreciable uncoupling of residual
      receptors from their immediate effector system). Pretreatment for 60 min with
      GnRH also caused a dose-dependent reduction in both spike and plateau phases of
      the GnRH effect on cytosolic Ca2+. This effect could not be overcome by
      stimulation with high concentrations of GnRH and appears, therefore, to reflect
      not only receptor loss, but, also, an additional inability of agonist-occupied
      GnRH receptors to elevate cytosolic Ca2+. The effect of KCl on cytosolic Ca2+ was
      similarly reduced by GnRH pretreatment, suggesting that desensitization of
      voltage-operated Ca2+ channels mediates desensitization of the plateau phase Ca2+
      response to GnRH. Such a mechanism could not, however, explain desensitization of
      the spike phase of the Ca2+ response to GnRH seen in normal or Ca2+ -free medium.
      Accordingly, the data reveal a novel mechanism for homologous desensitization to
      GnRH in which agonist-occupied GnRH receptors are rendered unable to mobilize
      intracellular Ca2+ and imply that desensitization of GnRH-stimulated Ins(1,4,5)P3
      production and/or action occurs.

PMID- 7588214
TI  - Forskolin inhibits protein kinase C-induced mitogen activated protein kinase
      activity in MC3T3-E1 osteoblasts.
AB  - We recently demonstrated that stimulation of DNA synthesis in MC3T3-E1
      osteoblasts involves cross-talk between protein kinase C (PKC)-dependent pathways
      and activation of possible nonreceptor tyrosine kinases. In the current
      investigation we examined whether the Raf-1/MAP kinase kinase (MKK)/mitogen
      activated protein kinase (MAPK) cascade integrates cross-talk between G protein
      coupled second messengers and protein tyrosine phosphorylation in osteoblasts. We
      investigated the effects on DNA synthesis, protein tyrosine phosphorylation, and
      Raf-1, MKK, and MAPK activities of PKC activation by phorbol 12-myristate 13
      acetate (PMA) and of cAMP elevation by forskolin (FSK) in MC3T3-E1 osteoblasts.
      We found that PMA-stimulated DNA synthesis was associated with increments in
      tyrosine phosphorylation of p44mapk (ERK1) and p42mapk (ERK2) and activation of
      Raf-1, MKK, and MAPK in these cells. FSK treatment of osteoblasts, which raised
      intracellular cAMP levels and inhibited DNA synthesis, blocked PKC-stimulated
      tyrosine phosphorylation of p44mapk (ERK1) and p42mapk (ERK2) as well as
      inhibited PKC-stimulated MAPK and Raf-1 activities. Despite this, PMA activated
      the intermediate MKK step of the Raf-1/MKK/MAPK cascade in the presence of FSK.
      The differential inhibition of PMA-stimulated Raf-1 and MKK activities by FSK
      suggests that PKC activates both Raf-1-dependent and -independent pathways in
      MC3T3-E1 osteoblasts. Moreover, the noncoordinate effects of FSK on PMA
      stimulated MKK and MAPK activities indicates the presence of a additional distal
      cAMP-dependent inhibitory mechanisms.

PMID- 7588219
TI  - Developmentally regulated expression of adrenal 17 alpha-hydroxylase cytochrome
      P450 in the mouse embryo.
AB  - Corticosterone is the major circulating glucocorticoid in adult mice and rats,
      and this is explained, in part, by the absence of 17 alpha-hydroxylase cytochrome
      P450 (P450c17) in adrenal glands of these rodents. During embryonic development,
      however, we discovered transient expression of P450c17 in a subset of
      adrenocortical cells in the fetal mouse adrenal. This differs from cholesterol
      side-chain cleavage cytochrome P450 and adrenodoxin, which are expressed
      continuously in most fetal adrenocortical cells from onset of expression at
      embryonic days 11-12 (E11-12) until term. Adrenal P450c17 transcripts are
      detectable in situ at E12.5 and increase in abundance from E12.5 to E14.5.
      Transcripts are then lost between E16.5 and term (E18.5) and are undetectable in
      situ in adrenal glands of adult mice. These results are consistent with the
      presence of pregnenolone 17 alpha-hydroxylase activity in adrenal homogenates of
      fetal but not adult mice. By using polymerase chain reaction, we determined that
      murine fetal (E14.5-15.5) adrenal glands contain messenger RNAs (mRNAs) encoding
      all of the steroid hydroxylases required to produce cortisol and corticosterone
      but little aldosterone synthase mRNA. Adrenal glands from adult mice contain
      mRNAs encoding steroid hydroxylases required to produce corticosterone and
      aldosterone but not cortisol (little P450c17 mRNA). The spatial and temporal
      expression patterns of P450c17 and aldosterone synthase mRNA, which differ from
      those of cholesterol side-chain cleavage cytochrome P450 and adrenodoxin, suggest
      that multiple factors must be required to program cell type- and species-specific
      expression of these steroid hydroxylases during embryonic development.

PMID- 7588224
TI  - Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid
      stability of components of the insulin secretory system in RIN 1046-38 cells.
AB  - It has been previously demonstrated that the enteric hormone glucagon-like
      peptide-1 (7-36 amide) (GLP-1) has acute effects on glucose-induced insulin
      secretion by RIN 1046-38 cells. In this study, we investigated the effects of
      extended exposure of RIN 1046-38 cells to GLP-1 and examine the mechanism by
      which GLP-1 synergizes with glucose in stimulating insulin secretion. Compared
      with cells cultured with glucose alone, incubation of cells with glucose plus 1
      or 10 nM GLP-1 for 12 or 24 h significantly increased insulin release by about 3
      fold, intracellular insulin content by 1.5-fold, and insulin messenger RNA (mRNA)
      by almost 2.5-fold. The insulinotropic effects of GLP-1 on RIN 1046-38 cells were
      accompanied by an up-regulation of both glucose transporter-1 (GLUT-1) and
      hexokinase I mRNA by about 2-fold. mRNA levels of GLUT-2 and glucokinase, which
      were low in controls, were unchanged by GLP-1 treatment. Treatment of cells with
      a transcription inhibitor, actinomycin D, demonstrated that elevated insulin mRNA
      levels after a GLP-1 exposure are mainly due to stabilization of the mRNA. In
      contrast, the elevated mRNA levels of GLUT-1 and hexokinase I are the result of
      increased transcription stimulated by GLP-1 exposure. Actinomycin D blunted the
      GLP-1 effect on insulin release but did not affect GLP-1 mediated elevation of
      insulin mRNA. This suggests that actinomycin D inhibits the transcription of the
      proteins necessary for insulin biosynthesis and insulin release, such as GLUT-1
      and hexokinase I. Our study suggests that the mechanisms by which extended
      exposure of RIN 1046-38 cells to GLP-1 increases glucose-stimulated insulin
      secretion include significant up-regulation of glucose-sensing elements.

PMID- 7588223
TI  - Regulation of insulin release by phospholipase C activation in mouse islets:
      differential effects of glucose and neurohumoral stimulation.
AB  - Rat islets respond to glucose stimulation with a marked first and second phase
      increase in insulin secretion. In contrast, mouse islets have a similar first
      phase response but little second phase secretion. In these studies, we determined
      if activation of phospholipase C (PLC) accounts for these differences in second
      phase insulin secretion in these two species. Stimulation of freshly isolated
      mouse and rat islets with 15 mM glucose resulted in comparable first phase
      insulin secretion; however, the second phase response from mouse islets was only
      doubled from 28 +/- 6 to 60 +/- 7 pg/islet.min compared with an increase from 24
      +/- 4 to 1064 +/- 93 pg/islet.min from rat islets. The addition of the muscarinic
      agonist carbachol (100 microM) in the presence of 15 mM glucose, however,
      markedly increased second phase insulin release from mouse islets to 801 +/- 80
      pg/islet.min. Similar increases in second phase insulin release from mouse islets
      were obtained with the addition of 500 nM of the protein kinase C activator
      tetradecanoyl phorbol acetate in the presence of 15 mM glucose. However, the
      incretin factor glucagon-like peptide-1, which elevates islet cAMP levels, had
      little effect on second phase insulin release in the mouse. An analysis of PLC
      mediated phosphoinositide (PI) hydrolysis revealed that 15 mM glucose increased
      inositol phosphate (IP) accumulation 0.5-fold above baseline in mouse islets
      compared with 3.7-fold in rat islets. In contrast, carbachol stimulated IP
      accumulation 3.5-fold in both mouse and rat islets. Analysis of PLC isozymes with
      isozyme specific monoclonal antibodies, demonstrated that mouse islets express 14
      +/- 4% of PLC-delta 1 and 18 +/- 6% of PLC-beta 1 compared with rat islets but
      similar amounts of the PLC-gamma 1 (117 +/- 16%). These findings suggest that the
      decreased second phase insulin secretory response in mouse compared with rat
      islets results, at least in part, from an inability of high glucose to stimulate
      comparable increments in PI hydrolysis. This lack of glucose responsiveness may
      be due to the pronounced underexpression of specific PLC isozymes in the mouse.

PMID- 7588226
TI  - Interferon-alpha and -gamma expression in the rat testis.
AB  - Interferon-alpha (IFN alpha), -beta, and -gamma are well known for their
      antiviral, antiproliferative, and immunoregulatory activities. Although several
      studies suggest an involvement of IFNs in the spermatogenic process, nothing is
      known about the possible production of these molecules within the testis.
      Moreover, the antiviral capabilities of testicular cells have not yet been
      explored despite their importance in the context of sexually transmissible
      diseases. Using reverse transcription-polymerase chain reaction, a cytopathic
      inhibition micromethod assay, and an enzyme-linked immunosorbent assay, the
      present study demonstrates for the first time that IFN alpha and -gamma are
      produced by testicular cells. IFN alpha protein and corresponding messenger RNA
      are expressed by peritubular, Sertoli, and germ cells. In vitro, IFN alpha
      production by Sertoli cells, peritubular cells, and early spermatids was
      inducible by the Sendai virus, whereas pachytene spermatocyte IFN alpha
      production was not triggered by this virus. Of all the testicular cell types
      tested, Sertoli cells by far produced the highest concentrations of IFN
      alpha/beta, followed by peritubular cells. Both IFN gamma messenger RNA and IFN
      gamma protein were found in early spermatids, but, in contrast, were not produced
      by peritubular cells, Sertoli cells, or pachytene spermatocytes. In conclusion,
      our study establishes the cellular distribution of IFNs within the seminiferous
      tubules and provides the basis for research into the possible involvement of IFNs
      in regulation of the spermatogenic process. To the best of our knowledge, our
      results afford the first insight on how the testicular antiviral defense system
      is organized.

PMID- 7588228
TI  - Glucocorticoids stimulate thyrotropin-releasing hormone gene expression in
      cultured hypothalamic neurons.
AB  - Although there is much evidence indicating that glucocorticoids (GC) inhibit the
      hypothalamic-pituitary-thyroid axis in both rat and man in vivo, there have been
      no previous studies on the direct effect of GC on hypothalamic TRH neurons in
      vitro. In this laboratory, we developed fetal rat (day 17) diencephalic neuronal
      cultures in the presence of 5'-bromo-2-deoxyuridine, a cell-differentiating agent
      that stimulates TRH gene expression. In 12 separate experiments, dexamethasone
      (Dex) induced a 2.2-fold increase in TRH content vs. the control value (P <
      0.01). Dex (10(-8)M) enhanced TRH messenger RNA (mRNA) 1.6-fold (n = 75 wells; P
      < 0.01) by nonisotopic in situ hybridization. On Northern blot analysis using a
      32P-labeled complementary RNA probe, TRH mRNA was enhanced 3-fold (n = 4; P <
      0.01). Nuclear run-on analysis revealed that Dex enhanced transcription 7.7 fold
      (n = 3; P < 0.01). We conclude that 1) Dex stimulates the expression of TRH
      peptide and TRH mRNA in cultured hypothalamic neurons; 2) the increase in TRH
      mRNA results (at least in part) from enhanced transcription; and 3) the reported
      in vivo depression of TRH in the paraventricular nucleus after GC stimulation
      suggests that this effect must be mediated indirectly on the TRH neuron.

PMID- 7588227
TI  - Ovine interferon-tau inhibits estrogen receptor up-regulation and estrogen
      induced luteolysis in cyclic ewes.
AB  - This study determined whether intrauterine injection of interferon-tau (IFN tau)
      could block luteolysis in cyclic ewes treated with a luteolytic dose of 17 beta
      estradiol benzoate (E) on day 12 of the estrous cycle. Thirty-two ewes were
      fitted with uterine catheters on day 5 of the estrous cycle and treated with
      recombinant ovine IFN tau (2 x 10(7) antiviral units/ewe/day) or control proteins
      (6 mg/day) by intrauterine injection from day 10 until hysterectomy. At 1900 h on
      day 12, all ewes received 750 micrograms E, im, and were hysterectomized 12, 24,
      36, or 48 h post-E administration. Plasma concentrations of progesterone declined
      in control animals but increased in IFN tau-treated ewes after E injection (P <
      0.01, treatment x day interaction). Likewise, total corpus luteum weight
      decreased in control but not IFN tau-treated ewes after E administration (P <
      0.02, treatment x time interaction). In control ewes, endometrial estrogen
      receptor (ER) messenger RNA (mRNA; P < 0.03) and progesterone receptor (PR) mRNA
      (P < 0.10) increased after 12 h, whereas concentrations of ER protein (P < 0.02)
      and PR protein (P < 0.04) increased after 24 h. In situ hybridization and
      immunohistochemical analyses indicated that ER gene expression increased first in
      the epithelium at 12 h and then in the stroma by 48 h, whereas PR gene expression
      first increased in the stroma and then in the epithelium. In control ewes,
      endometrial oxytocin receptor (OTR) density increased (P < 0.10) after 12 h, with
      the largest increase occurring between 36-48 h. In IFN tau-treated ewes,
      endometrial ER mRNA and protein and OTR density did not increase after E
      administration. Levels of PR mRNA increased (P < 0.01) between 12-36 h, but
      decreased after 36 h. PR mRNA abundance increased between 12-36 h in the stroma,
      but not in the epithelium. Concentrations of PR protein were low and did not
      change in IFN tau-treated ewes. Immunoreactive PR protein was present at low
      levels in the stroma of all IFN tau-treated ewes. The results indicate that
      induction of luteolysis by E in control ewes involved sequential increases in
      endometrial ER mRNA and ER protein in the epithelium that preceded maximal
      increases in OTR density. Intrauterine injection of recombinant ovine IFN tau
      prevented luteolysis by inhibiting estrogen-induced increases in endometrial ER
      and OTR gene expression.

PMID- 7588225
TI  - Single tyrosine substitution in the insulin-like growth factor I receptor
      inhibits ligand-induced receptor autophosphorylation and internalization, but not
      mitogenesis.
AB  - The tyrosine kinase domains of the insulin and insulin-like growth factor I (IGF
      I) receptors play an essential role in signal transduction. After ligand binding,
      these receptors undergo autophosphorylation, with a cluster of three tyrosines
      (residues 1131, 1135, and 1136 in the IGF-I receptor) being the first to be
      phosphorylated. Mutation of the ATP-binding site or substitution of this triple
      tyrosine cluster in the catalytic domain blocks essentially all of the functions
      of these receptors. Using stably transfected NIH-3T3 cell lines, we studied the
      effect of a mutation of tyrosine 1131 of the triple tyrosine cluster of the IGF-I
      receptor to phenylalanine. This mutation significantly reduced IGF-I-induced beta
      subunit autophosphorylation, whereas phosphorylation of the endogenous substrate
      IRS-1 was unaffected. Despite the reduction in autophosphorylation and receptor
      internalization, IGF-I-induced thymidine incorporation and cellular proliferation
      were unaffected. Thus, the extent of receptor autophosphorylation and
      internalization does not appear to be a limiting factor for IGF-I-stimulated
      mitogenesis.

PMID- 7588229
TI  - Anti-mullerian hormone and anti-mullerian hormone type II receptor messenger
      ribonucleic acid expression in rat ovaries during postnatal development, the
      estrous cycle, and gonadotropin-induced follicle growth.
AB  - During fetal development, anti-mullerian hormone (AMH) is produced only by
      Sertoli cells, but postnatally, granulosa cells also produce this peptide
      growth/differentiation factor. We recently identified a candidate AMH type II
      receptor (AMHRII). In the present study, postnatal ovarian AMH and AMHRII
      messenger RNA (mRNA) expression was studied by in situ hybridization and
      ribonuclease protection. In ovaries from adult rats, AMH and AMHRII mRNAs were
      found to be mainly expressed in granulosa cells from preantral and small antral
      follicles. Corpora lutea and large antral follicles express little or no AMH and
      AMHRII mRNA, and primordial follicles and oocytes appeared to be AMH and AMHRII
      mRNA negative. Thecal and interstitial cells express no detectable AMH mRNA and
      little or no AMHRII mRNA. The colocalization of AMH and AMHRII mRNAs in granulosa
      cells of specific follicle types suggests that actions of AMH via AMHRII are
      autocrine in nature. There is a decreased level of AMH and AMHRII mRNA expression
      when follicles become atretic. Both mRNA species are eventually lost from atretic
      follicles, although AMHRII mRNA expression seems to persist somewhat longer than
      AMH mRNA. During the estrous cycle, no marked changes in the patterns of AMH and
      AMHRII mRNA expression were detected, except at estrus, when expression of both
      mRNA species in preantral follicles was decreased compared to that on the other
      days of the cycle. On postnatal day 5, total ovarian AMH mRNA expression is low
      and is located in small preantral follicles. During the first weeks of postnatal
      development, AMH mRNA expression in preantral follicles increases, and the later
      formed small antral follicles also express AMH mRNA. In contrast, AMHRII mRNA is
      expressed on postnatal day 5 at a higher level than AMH mRNA, but cannot be
      localized to specific cell types. From postnatal day 15 onward, AMHRII mRNA
      expression becomes more restricted to the preantral and small antral follicles.
      Treatment of prepubertal rats with GnRH antagonist (Org 30276) and human
      recombinant FSH (Org 32489) or with GnRH antagonist and estradiol benzoate
      resulted in follicle growth and inhibition of AMH and AMHRII mRNA expression in
      some, but not all, preantral and small antral follicles. These results indicate
      that FSH and estrogens may play a role in the down-regulation of AMH and AMHRII
      mRNA expression in vivo when small antral follicles differentiate into large
      antral follicles. Furthermore, the FSH surge on the morning of estrus may inhibit
      AMH and AMHRII mRNA expression in preantral follicles.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7588230
TI  - Prostaglandin F2 alpha mediates ovarian sterol carrier protein-2 expression
      during luteolysis.
AB  - In the corpus luteum, prostaglandin F2 alpha (PGF2 alpha) appears to be a
      physiological agent with both antisteroidogenic and luteolytic actions. It is
      hypothesized that the antisteroidogenic action of PGF2 alpha acts through altered
      transport of cholesterol to the mitochondrial cytochrome P450 side-chain cleavage
      enzyme (P450scc). However, the effect of PGF2 alpha on the expression of the
      putative cholesterol transport protein, sterol carrier protein-2 (SCP2; 13.2
      kilodaltons), has not been examined. In this study, the decline in serum
      progesterone after PGF2 alpha injection was examined in parallel with altered
      ovarian SCP2, P450scc, and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD)
      protein and messenger RNA (mRNA) levels. Rats (28 days old) were treated with 8
      IU PMSG to induce follicular development and ovulation. Ten days after ovulation,
      animals were treated with PGF2 alpha (single or multiple injections; 100-250
      micrograms each) or left untreated. Ovarian SCP2, P450scc, and 3 beta HSD protein
      and mRNA levels were examined 0 (time zero), 4, and 8 h post-PGF2 alpha treatment
      using Western and Northern blot analysis. SCP2 mRNA levels were also examined
      using a highly sensitive ribonuclease protection assay that detects a 429-base
      pair SCP2-mRNA specific sequence. The results indicate that serum progesterone
      was significantly reduced 4 and 8 h after PGF2 alpha injections (P < 0.001; n =
      6/time point). The decline in progesterone paralleled a 50-60% reduction in 3
      beta HSD protein and mRNA levels by 4 h post-PGF2 alpha. Protein and mRNA levels
      for 3 beta HSD returned to control values by 8 h post-PGF2 alpha treatment.
      P450scc expression was also reduced at 4 h (44-54%), but by 8 h, both protein and
      mRNA levels had increased above the normal control levels (P < 0.02). In
      contrast, the 0.8-kilobase SCP2-specific mRNA transcript was reduced to 50% and
      80% of the pre-PGF2 alpha treatment level at 4 and 8 h, respectively (P < 0.01).
      SCP2 ribonuclease protection assay analysis also indicated that SCP2 mRNA levels
      were reduced 65% (P < 0.03) and 85% (P < 0.01) by 4 and 8 h post-PGF2 alpha
      treatment compared to those in time zero ovarian tissue. Consistent with the loss
      of SCP2 mRNA expression, Western blot analysis indicated that a 15-kilodalton
      SCP2-immunoreactive protein (presumably the pro-SCP2 form) was significantly
      reduced or absent in the PGF2 alpha treated animals (P < 0.04).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7588231
TI  - Induction of tissue inhibitor of metalloproteinase 3 gene expression during in
      vitro decidualization of human endometrial stromal cells.
AB  - Endometrial stromal differentiation (decidualization) is essential for
      implantation of the developing blastocyst. To investigate the process of
      progesterone (P)-induced decidualization of human endometrial stromal cells
      (ESC), a complementary DNA library enriched with P-induced genes was constructed
      from cultured human ESC by subtractive hybridization and the polymerase chain
      reaction. One of the isolated clones was the complementary DNA for the tissue
      inhibitor of metalloproteinase-3 (TIMP-3), a recently identified member of the
      human TIMP family. When human ESC were cultured in the presence of P for 6 days,
      the induction of TIMP-3 messenger RNA (mRNA) expression was observed by Northern
      blotting. In contrast, the marked induction of PRL mRNA expression and
      morphological changes were observed after 9 days of culture. P-induced TIMP-3
      mRNA expression was dose dependent, and this induction was inhibited by the
      antiprogestin RU486. Estrogen did not induce TIMP-3 mRNA expression under similar
      conditions. In situ hybridization analysis of endometria from nonpregnant women
      revealed that the TIMP-3 mRNA expression was restricted to predecidualized
      stromal cells. At the feto-maternal interface, TIMP-3 expression was observed in
      fetal extravillous trophoblasts that had invaded the maternal decidual tissues as
      well as in the maternal decidual cells. These findings suggest that TIMP-3 is a
      sensitive indicator of ESC decidualization, and that the induction of TIMP-3
      expression in decidual cells and trophoblasts may be important in the regulation
      of trophoblast invasion.

PMID- 7588232
TI  - Purified rat acid-labile subunit and recombinant human insulin-like growth factor
      (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the
      absence of IGFs.
AB  - Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150
      kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and
      an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs
      directly. This complex sequesters IGFs in plasma, thereby providing a potential
      reservoir of the growth factors for tissues while constraining their potential
      hypoglycemic effects. Although it has been thought that IGFBP-3 must first bind
      IGF-I or IGF-II before it can complex with ALS to form the 150-kDa complex, we
      recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are
      abundant in adult rat serum. We now demonstrate that IGFBP-3 and rat (r)ALS can
      form 150-kDa complexes in the absence of IGFs. ALS was purified from rat serum by
      anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose
      column to which human (h) IGFBP-3 had been noncovalently bound. The preparation
      contained less than 0.1 ng IGF-I/microgram(s) purified ALS. In the absence of
      IGF, radiolabeled (r)ALS and recombinant hIGFBP-3 formed complexes that could be
      immunoprecipitated by antiserum to hIGFBP-3; these complexes were identified by
      direct quantitation of the precipitated radioactivity or by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDA-PAGE). Inclusion of IGF-I in the
      incubation increased complex formation. Complex formation also was demonstrated
      by incubation of unlabeled rALS with hIGFBP-3, followed by affinity cross
      linking. Complexes were fractionated by SDS-PAGE, blotted, and shown to contain
      unoccupied IGF-binding sites by their ability to bind radioiodinated IGF-II. In
      addition, when rALS was subjected to SDS-PAGE and blotted, radioiodinated
      recombinant hIGFBP-3 bound to the 85-kDa protein. In this experiment IGFBP-3
      binding was slightly increased by coincubation with IGF-I. Thus, purified rALS
      can form a 150-kDa complex with hIGFBP-3 in the absence of IGF in vitro. The
      efficiency of complex formation was increased to variable extents by coincubation
      with IGF-I depending on the assay method.

PMID- 7588233
TI  - Biological activity and immunological reactivity of human prolactin mutants.
AB  - We examined the biological activity and immunological reactivity of four mutants
      of human PRL. Two were mutants that changed the ability of human PRL to inhibit
      rat PRL storage when transfected into a rat pituitary cell line:mutations S34A
      and N31T. Two mutations were in regions of PRL that are highly conserved. One,
      des(3-11)-PRL, removed the N-terminal cystine loop that most PRLs, except those
      from certain fish, have, and no GHs have. The other, S90A, mutated a serine that
      is present in all PRLs but those from some fish and in all GHs. The immunological
      properties of des(3-11)-PRL were reduced 10-fold compared to those of wildtype
      human PRL in a RIA using NIH antihuman PRL-3, AFP C11580; the others were similar
      to those of wild-type PRL. The biological activity of des(3-11)-PRL was the most
      affected; activity was reduced about 8-fold compared to that of wild-type PRL in
      the Nb2 cell assay. The activities of the others were similar to that of the wild
      type. Serine 90 may be partially buried by loops connecting the alpha-helixes.
      The mutation of serine 90 did not affect the stability of the molecule in vitro,
      determined by comparing the red shift in tryptophan fluorescence that occurs with
      increasing concentrations of urea in S90A and wild-type PRL. The activity of S34A
      and N31T mutations indicates there is no correlation between biological activity
      and ability to affect storage. The N-terminal cystine loop may be conserved
      because it is needed for biological activity, but the conservation of serine 90
      in GH and PRL must be determined by other properties, such as spacial
      requirements.

PMID- 7588234
TI  - Estrogen stimulation and tamoxifen inhibition of leiomyoma cell growth in vitro
      and in vivo.
AB  - Uterine leiomyomas (fibroids) are the most common gynecological neoplasms and may
      be associated with significant morbidity. Recently, we described a rat model
      (Eker rat) of fibroid development in which reproductive tract leiomyomas develop
      spontaneously with high frequency. The present studies describe the estrogen and
      antiestrogen responsiveness of an Eker rat leiomyoma-derived cell line in vitro
      and a nude mouse xenograft system in vivo. In this cell line, estradiol
      stimulated growth in estrogen-depleted medium, whereas the nonsteroidal
      antiestrogen tamoxifen maximally inhibited cell proliferation in medium
      containing 10% charcoal-stripped serum. Proliferation was also decreased by the
      biologically active tamoxifen metabolite 4-hydroxytamoxifen; the metabolite was
      more effective than the parent compound in exerting this growth inhibition.
      Compared to placebo-treated controls, estradiol increased the size of tumors that
      developed in a nude mouse xenograft system, whereas tamoxifen increased tumor
      latency and decreased tumor size. This study of leiomyoma cells in a well defined
      system suggests that antiestrogens may prove efficacious in the treatment of this
      clinically important neoplasm.

PMID- 7588236
TI  - Nature of endothelin binding in the porcine ovary.
AB  - We investigated the nature of endothelin (ET) binding in the porcine ovary. We
      demonstrated the presence of high affinity (Kd = 0.72; 95% confidence interval =
      0.43-1.1 nM) binding sites for ET-1 in the porcine ovary. The binding capacity
      for this ET-1-specific binding site was 97 pmol/micrograms DNA (95% confidence
      interval = 90-107). Autoradiographic studies showed that putative ET receptors
      reside in the granulosa cell layer of the maturing Graafian follicle and in the
      vascular components of the corpora lutea. The relative abundance of ET receptors
      was greatest in granulosa cells of large antral follicles, whereas ET binding was
      absent in granulosa cells of preantral follicles and in luteal cells. ET binding
      by cultured granulosa cells was further characterized by RRA and shown to exhibit
      a rank order of binding affinities for different ET isopeptides. The observed
      rank order indicates that the ET receptors present on granulosa cells are of the
      ET(A) receptor subtype. The radioreceptor studies also indicated that granulosa
      cells collected from large antral follicles (9-10 mm in diameter) have a greater
      binding capacity for [125I]ET-1 in culture than granulosa cells collected from
      smaller follicles. When cultured granulosa cells were exposed to 100 nM ET-1 or
      14 nM 12-O-tetradecanoylphorbol 13-acetate overnight, the percentage of specific
      [125I]ET-1 binding was reduced (12% and 50%, respectively), indicating a down
      regulation of the ET receptor by these treatments. In summary, we have
      characterized the distribution, isopeptide specificity, relative abundance, and
      down-regulation of putative ovarian endothelin receptors of subtype ET(A) on
      swine granulosa cells. Such results in conjunction with other available
      literature strongly suggest that granulosa cells of maturing Graafian follicles
      are targeted by ET-1. An additional physiological role for ET-1 in the ovary is
      suggested by the presence of putative ET receptors in the vasculature of the
      corpus luteum.

PMID- 7588235
TI  - Decreased stathmin expression does not affect the actions of human
      choriogonadotropin or epidermal growth factor in Leydig tumor cells.
AB  - Although hCG and mouse epidermal growth factor (mEGF) activate different
      signaling systems in a clonal strain of murine Leydig tumor cells (designated MA
      10), both compounds ultimately elicit several common effects such as increased
      steroidogenesis, decreased transcription of the LH receptor gene and attenuation
      of adenylyl cyclase. A 21-kilodalton protein whose phosphorylation state
      increases after hCG and mEGF stimulation has previously been described and
      identified as stathmin. To determine whether stathmin is involved in the
      signaling pathways of hCG and mEGF, an expression vector containing the full
      length stathmin complementary DNA in an antisense orientation was constructed and
      used to establish two novel clonal MA-10 cell lines that have a decreased level
      of stathmin expression. Characterization of these mutant cell lines revealed no
      differences from MA-10 cells or neomycin-resistant subclones of MA-10 cells with
      respect to the ability of hCG or mEGF to increase steroidogenesis, decrease
      transcription of the LH receptor, or attenuate the adenylyl cyclase activity.
      Thus, it appears that stathmin is not involved in mediating the common actions of
      hCG and mEGF in MA-10 cells.

PMID- 7588237
TI  - Development of adrenocorticotropin-(1-39) and precursor peptide secretory
      responses in the fetal sheep during the last third of gestation.
AB  - Although it is known that concentrations of immunoreactive ACTH increase during
      late gestation in fetal sheep plasma, the nature of the ACTH has not been well
      characterized. We used two-site immunoradiometric assays to separately measure
      high mol wt ACTH precursors (POMC and pro-ACTH) and ACTH-(1-39) in plasma of
      fetal sheep with chronic arterial and venous catheters. We compared the ratio of
      these peptides as a function of gestational age under basal conditions and in
      response to exogenous vasopressin and/or corticotropin-releasing hormone. Under
      basal conditions, the concentration of precursors was not changed throughout the
      last third of gestation; however, ACTH-(1-39) increased significantly approaching
      term. The molar ratio of precursors to ACTH-(1-39), therefore, decreased from
      15.8 +/- 1.0 at 110 days to 7.9 +/- 0.6 at 140 days gestation. At all gestational
      ages, vasopressin and corticotropin-releasing hormone increased ACTH-(1-39) and
      precursors, albeit with different time courses. At 120 days gestation, arginine
      vasopressin plus CRH produced synergistic increases in ACTH-(1-39) and
      precursors, whereas the response was only additive at other ages. The present
      results indicate that the elevation in the resting plasma immunoreactive ACTH
      concentration that occurs near term is constituted by an increase in the
      concentration of ACTH-(1-39) relative to those of POMC and pro-ACTH, which may
      have further physiological significance. Also, CRH and AVP are potent stimulators
      of both ACTH-(1-39) and ACTH precursors.

PMID- 7588238
TI  - Interferon-gamma increases intracellular calcium and inositol phosphates in
      primary human thyroid cell culture.
AB  - Interferon-gamma (IFN gamma) is believed to play a role in the pathogenesis of
      autoimmune thyroid disease, as it is known to exert diverse effects on thyroid
      metabolism. These include induction of human leukocyte antigen class II
      expression, inhibition of gene expression of thyroglobulin and thyroid
      peroxidase, as well as inhibition of cellular proliferation. However, the
      mechanism of action of IFN gamma in thyrocytes has not been clearly defined. We
      studied the action of IFN gamma on the production of inositol phosphates and
      intracellular Ca2+ mobilization in primary cultures of human thyrocytes using the
      fluorescent Ca2+ indicator fura-2. IFN gamma increased the production of inositol
      mono-, bis-, and trisphosphates and caused a dose-dependent increase in
      intracellular Ca2+ ([Ca2+]i) at 37 C. Preincubation with 12-O
      tetradecanoylphorbol-13-acetate, which activates protein kinase C, resulted in
      the abolition of the IFN gamma response, suggesting that protein kinase C was
      involved in a negative feedback loop resulting in inhibition of IFN gamma-induced
      [Ca2+]i rise. Prior release of intracellularly stored Ca2+ with thapsigargin, the
      microsomal Ca2+ pump inhibitor, also abolished the response of IFN gamma.
      Mobilization of [Ca2+]i resulted in Ca2+ entry across the plasma membrane, which
      could be blocked by La3+, the inorganic Ca2+ antagonist. The tyrosine protein
      kinase inhibitor, genistein, inhibited the production of inositol phosphates and
      the elevation of [Ca2+]i induced by IFN gamma, but had no effect on ATP,
      suggesting that tyrosine protein kinase is involved in the signaling transduction
      of IFN gamma. We conclude that the mobilization of intracellular Ca2+ and the
      production of inositol phosphates are two important signaling events for the
      action of IFN gamma in human thyrocytes.

PMID- 7588240
TI  - Interleukin-1 beta-converting enzyme-related proteases (IRPs) and mammalian cell
      death: dissociation of IRP-induced oligonucleosomal endonuclease activity from
      morphological apoptosis in granulosa cells of the ovarian follicle.
AB  - The Caenorhabditis elegans death susceptibility gene, ced-3, has a number of
      homologs in vertebrate species, including interleukin-1 beta (IL-1 beta)
      converting enzyme (ICE), Ich-1long, and CPP32. These genes, which encode a family
      of related proteases, have been shown to induce apoptosis when transfected into
      eukaryotic cells. However, it remains to be determined whether these proteases
      are involved in apoptotic cell death under physiological conditions. The purpose
      of these studies was to examine the role of ICE-related proteases (IRPs) in
      apoptosis using a physiologically relevant model system, the ovarian follicle.
      Somatic granulosa cells within ovarian follicles undergo apoptosis during
      follicular atresia, a process responsible for the depletion of greater than 95%
      of the follicles established in the postnatal ovary. To accomplish these studies,
      we cloned partial rat complementary DNAs encoding ICE, Ich-1, and CPP32 and used
      these complementary DNAs to examine the gonadotropin regulation of ICE, Ich-1,
      and CPP32 gene expression in the immature rat ovary. We also examined levels of
      ICE activity in healthy and atretic rat follicles by monitoring the conversion of
      exogenous pro-IL-1 beta to the active cytokine, and then evaluated the actions of
      recombinant IL-1 beta on apoptosis in follicles incubated in vitro. Finally, we
      tested the requirement for IRP activity in granulosa cell apoptosis and
      follicular atresia by incubating follicles without and with IRP inhibitors.
      Northern blot analysis of total RNA samples indicated that gonadotropin-promoted
      follicular survival was associated with reduced ovarian expression of messenger
      RNAs encoding Ich-1 and CPP32. In contrast, ICE messenger RNA levels were
      extremely low and were not affected by gonadotropin treatment. We were also
      unable to detect ICE activity in proteins extracted from either healthy or
      atretic rat follicles, collectively suggesting that ICE per se may not function
      in granulosa cell death. As another approach to determine whether ICE is involved
      in atresia, healthy antral follicles were isolated from ovaries of gonadotropin
      primed immature rats and incubated for 24 h in the absence or presence of 100
      ng/ml transforming growth factor-alpha (TGF alpha) without and with 100 ng/ml IL
      1 beta. Granulosa cells within follicles incubated in medium alone exhibited
      extensive levels of apoptosis, and this onset of apoptosis was prevented by the
      inclusion of TGF alpha. Addition of IL-1 beta did not alter basal levels of
      apoptosis nor did the cytokine antagonize TGF-alpha-promoted follicle survival,
      providing additional evidence that ICE activity is not required for atresia to
      occur.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588241
TI  - Thyroid cell injury is an initial event in the induction of autoimmune
      thyroiditis by iodine in obese strain chickens.
AB  - The present study examines the role of thyroid cell injury in the initiation of
      autoimmune thyroiditis by iodine in Obese strain (OS) chickens, a strain
      genetically susceptible to spontaneous autoimmune thyroiditis. OS and normal
      strain chickens were placed on an iodine depletion regimen started in ovo. This
      regimen is known to prevent thyroiditis in OS chickens. The chickens were
      injected with NaI every 24 h for up to 7 days starting at 3 weeks of age. Both
      strains showed evidence of mild thyrocyte injury 12 h after NaI. However,
      significant and sustained infiltration, beginning 24 h after NaI, was seen only
      in the OS. The infiltrating cells were primarily mononuclear. Polymorphonuclear
      cells were not observed. Immunohistological analysis showed the infiltrate to be
      composed of CD8 T cells, CD4 T cells, B cells, and macrophages in the ratio
      40:20:22:17. The infiltration was sustained and progressive for at least 7 days.
      Thyroid infiltration after NaI repletion was significantly reduced in OS chickens
      tolerized to thyroglobulin at hatching. Prior treatment with the antioxidant drug
      ethoxyquin completely prevented both the thyrocyte injury and the infiltration
      induced by iodine. Treatment with antioxidant drugs had no effect on the uptake
      and incorporation of iodine by the thyroid. In summary, 1) iodine caused
      thyrocyte injury in both OS and normal chickens. 2) The injury was followed by
      cellular infiltration in the OS but not in normal chickens. 3) The infiltration
      appeared to be immune mediated in being primarily lymphocytic and at least
      partially thyroglobulin sensitive. 4) Prevention of thyroid injury by antioxidant
      drug treatment also prevented infiltration. We conclude that thyroid cell injury
      may be an initial event in the induction of autoimmune thyroiditis by iodine.

PMID- 7588242
TI  - Roles of insulin-like growth factor (IGF) receptors and IGF-binding proteins in
      IGF-II-induced proliferation and differentiation of L6A1 rat myoblasts.
AB  - Insulin-like growth factor II (IGF-II) stimulates the proliferation and
      differentiation of rat myoblasts. Previous studies suggest that these response
      are mediated by the IGF-I receptor, but the IGF-II/mannose 6-phosphate receptor
      was recently implicated in differentiation of mouse myoblasts. L6A1 myoblasts
      synthesize IGF-binding protein-4 (IGFBP-4), IGFBP-5, and IGFBP-6, which modulate
      IGF action. We studied the roles of IGF receptors and IGFBPs in L6A1 myoblast
      proliferation and differentiation by comparing the effects of IGF-II and a number
      of IGF-II mutants with decreased affinities for IGF receptors and/or IGFBPs. IGF
      II induced concentration-dependent proliferation with a maximum increase of 47%;
      half-maximal proliferation was seen with approximately 50 ng/ml. [Arg54,
      Arg55]IGF-II bound to the IGF-I receptor with slightly lower affinity than IGF
      II, did not bind to the IGF-II/mannose 6-phosphate receptor, and bound to IGFBPs
      secreted by myoblasts with approximately 16-fold decreased affinity. It induced
      proliferation with equal potency to IGF-II. [Leu27]IGF-II, which did not bind to
      the IGF-I receptor but bound to the IGF-II/mannose 6-phosphate receptor and
      IGFBPs with slightly lower affinity than IGF-II, had a markedly impaired
      proliferative effect, inducing proliferation only at high concentrations. [Thr48,
      Ser49, Ile50]IGF-II, which bound to the IGF-I receptor with slightly lower
      affinity than IGF-II but did not substantially bind to the IGF-II/mannose 6
      phosphate receptor or IGFBPs, induced proliferation with approximately 5-fold
      greater potency than IGF-II. The order of potency in inducing myoblast
      differentiation was the same, although there was less difference in the relative
      potencies of IGF-II and mutants. Coincubation of recombinant human (rh) IGFBP-6
      in molar excess with IGF-II inhibited myoblast proliferation and differentiation.
      rhIGFBP-6 was slightly less potent did not inhibit proliferation or proliferation
      or differentiation induced by [Thr48,Ser49,Ile50]IGF-II. These results suggest
      that 1) IGF-II-induced proliferation and differentiation of L6A1 myoblasts are
      predominantly mediated by the IGF-I receptor; 2) the IGF-II/mannose 6-phosphate
      receptor is not required for these actions of IGF-II; 3) nevertheless, the IGF
      II/mannose 6-phosphate receptor may be capable of mediating these actions; and 4)
      IGFBPs secreted by myoblasts inhibit IGF actions.

PMID- 7588243
TI  - Dexamethasone regulates somatostatin receptor subtype messenger ribonucleic acid
      expression in rat pituitary GH4C1 cells.
AB  - Ligand binding studies have shown that glucocorticoids down-regulate somatostatin
      receptor (sst) concentration in several endocrine target cells and cell lines
      including GH4C1 cells. However, it has not been determined whether this decrease
      in sst number occurred via transcriptional and/or posttranscriptional events. In
      the present study, we have investigated the effect of dexamethasone (Dex)
      treatment (1 microM) of GH4C1 cells for up to 48 h on the steady state level of
      messenger RNA (mRNA) for sst1, sst2, and sst3, the predominant isoforms expressed
      in this cell line, by solution hybridization-nuclease protection analysis.
      Exposure of GH4C1 cells to Dex for 2 h increased sst1 mRNA levels 2.5-fold and
      sst2 1.5-fold compared with controls (Con). Prolonged exposure, however, resulted
      in a decrease in mRNA levels of sst1 to 50% and sst2 to 30% of Con by 24-48 h. In
      contrast, sst3 mRNA levels were unchanged at 2 h, decreased to 30% of Con by 6 h,
      and remained decreased for up to 24 h. Longer exposure resulted in a dramatic
      increase in expression, reaching 350% of Con by 48 h. The Dex effect on
      expression of all subtypes was dose dependent, maximal at 10 nM. Steroid hormone
      regulation of sst mRNA expression in GH4C1 cells proved to be complex. Exposure
      to Dex for 24 h, as expected, decreased expression of all subtypes. Progesterone,
      however, increased sst1 mRNA levels, decreased sst3 levels, but was without
      effect on sst2; treatment with estrogen and testosterone increased expression of
      all three subtypes. Nuclear run-on assays indicated that the Dex-induced changes
      in sst1 and sst2 mRNA levels were associated with congruent changes in the
      transcription rate of sst genes. Thus, glucocorticoids regulate sst expression in
      GH4C1 cells, at least in part, by controlling the rate of transcription of sst
      genes.

PMID- 7588244
TI  - Molecular basis of estrogen regulation of Hageman factor XII gene expression.
AB  - Estrogen therapy has been reported to cause multiple alterations in hemostasis
      and to increase blood levels of several procoagulants, including Hageman factor
      [factor XII (FXII)]. Liver FXII gene expression has been investigated in
      ovariectomized rats, treated or not with 17 beta-estradiol. A 6-fold stimulation
      of FXII gene transcription was observed in treated compared to untreated animals,
      indicating that 17 beta-estradiol is able to induce FXII gene expression in vivo.
      We have recently shown that human FXII promoter contains an imperfect palindrome,
      5'-GGGCAnnnTGACC-3', at position -43/-31 resembling the consensus estrogen
      responsive element (ERE). Portions of different length of the FXII promoter were
      fused to the chloramphenicol acetyltransferase (CAT) coding sequence and
      transiently cotransfected with human estrogen receptor (ER) into NIH3T3 and HepG2
      cells in the presence or absence of 17 beta-estradiol. A 230-base pair fragment
      of FXII promoter, spanning nucleotides - 181/49, conferred a strong estrogen
      responsiveness to the CAT reporter gene, suggesting that a functional ERE resides
      in this region. Cognate receptors, such as those for thyroid hormone or retinoic
      acid, did not stimulate CAT activity. Gel mobility assays demonstrated a specific
      interaction between ER and the 230-bp FXII promoter fragment containing the
      putative ERE palindrome. Similar results were obtained when an oligonucleotide
      spanning the consensus ERE was used; the complex between ER and FXII promoter
      sequences was supershifted after the addition of an anti-ER monoclonal antibody.
      Insertion of FXII-ERE into the heterologous thymidine kinase promoter conferred a
      strong estrogen responsiveness that was abolished by mutations of the 5'-half of
      the palindrome. These results represent the first demonstration at the molecular
      level of the regulation of a blood coagulation factor gene by 17 beta-estradiol
      as well as the first identification of a functional ERE within this class of
      genes.

PMID- 7588246
TI  - Tyrosine phosphorylation of the growth hormone (GH) receptor and Janus tyrosine
      kinase-2 is involved in the insulin-like actions of GH in primary rat adipocytes.
AB  - The nature of tyrosine phosphorylations induced by GH in relation to the insulin
      like metabolic effects in primary rat adipocytes was investigated. Unlike other
      cells, e.g. 3T3-F442A fibroblast, in which GH is believed to initiate cell
      differentiation through activation of the Janus tyrosine kinase-2 (JAK2), the
      adipocytes are metabolically active and fully differentiated cells that do not
      proliferate. Thus, it cannot be assumed that the same molecular mechanisms relay
      the acute insulin-like effects of GH. In adipocytes responsive to these effects,
      we found that GH induced tyrosine phosphorylation of a 114-kilodalton membrane
      protein, identified as the GH receptor, and a 130-kilodalton cytosolic protein,
      identified as JAK2. In contrast, these phosphorylations were not seen in
      adipocytes refractory to these effects of GH. The GH concentration dependency
      (ED50,1-2 nM) of these phosphorylations coincided with the increase in
      lipogenesis and the decrease in noradrenaline-induced lipolysis caused by the
      hormone. In analogy with the effects of insulin, the onset of phosphorylation was
      rapid (t1/2, < 1 min) and preceded the metabolic responses. The observations that
      a small fraction of the receptor pool became tyrosine phosphorylated and that the
      level of phosphorylation induced by GH decreased at higher GH concentrations
      agree with the concept that GH-induced dimerization of the receptor is necessary
      for signal transduction. We conclude that tyrosine phosphorylation of JAK2 and
      the GH receptor seems to be involved in the signal transduction mechanism leading
      to the insulin-like effects of GH in adipocytes. Importantly, the signal pathways
      for GH and insulin clearly differ at the receptor level, but seem to converge at
      or before the level of insulin receptor substrate 1 or 2 phosphorylation that has
      been shown to occur in response to both of these hormones.

PMID- 7588245
TI  - Repression of glucocorticoid receptor-mediated transcriptional activation by
      unliganded thyroid hormone receptor (TR) is TR isoform-specific.
AB  - Two genes, c-ErbA alpha and c-ErbA beta, generate at least three functional T3
      receptor (TR) isoforms in the rat: TR alpha-1, TR beta-1, and TR beta-2. The
      latter is an N-terminal splice variant of TR beta-1 whose expression is high in
      the pituitary gland, whereas the other isoforms are more widely expressed. It is
      believed that TR beta-2 might play an important role in the pituitary, but no
      specific biological activities have been defined. Using in vitro translated
      receptors, we were unable to detect striking isoform-specific differences in T3
      binding, DNA binding, homodimerization and heterodimerization activities with
      retinoid X receptor in the electrophoretic mobility assay, or T3-dependent
      repression and activation of basal transcription in transfection assays. The N
      terminus of TR beta is completely dispensible for these activities. However, we
      found that unliganded TR alpha-1 and TR beta-1, but not TR beta-2, can repress
      glucocorticoid receptor-mediated transcriptional activation if the reporter gene
      promoter contains binding sites for both receptor species. TR beta-2 also
      synergizes most efficiently with the glucocorticoid receptor in the presence for
      the of T3. The TR beta-2-specific N-terminus is required for these effects. This
      result indicates that the relative abundance of specific TR isoforms may
      determine the with the glucocorticoid receptor in the presence of T3. The TR beta
      2 specific N-terminus is required for these effects. This result indicates that
      the relative abundance of specific TR isoforms may determine the quantitative
      response of a gene that is regulated by T3 and glucocorticoids. In particular,
      pituitary TR beta-2 may be an important mediator of GH gene expression, which is
      regulated by both of these hormones.

PMID- 7588239
TI  - Regulation of cytochrome P4501B1 in cultured rat adrenocortical cells by cyclic
      adenosine 3',5'-monophosphate and 2,3,7,8- tetrachlorodibenzo-p-dioxin.
AB  - Cytochrome P4501B1 (CYP1B1), which is responsible for metabolism of 7,12
      dimethylbenz[a]anthracene in the rat adrenal gland, is partially dependent on
      ACTH in vivo. The regulation of CYP1B1 and possible involvement in
      steroidogenesis have been characterized in cultured rat adrenocortical cells.
      Relatively high basal expression of CYP1B1 is maintained in vitro and is,
      therefore, independent of ACTH. CYP1B1 expression is elevated 4-fold in primary
      cultures of fasciculata cells after 24 h of ACTH treatment, as measured by
      selective 7,12-dimethylbenz[a]anthracene metabolism, immunoblot analysis, and
      parallel changes in the 5.2-kilobase CYP1B1 messenger RNA (mRNA). Corticosterone
      synthesis was stimulated about 40-fold in these cells after this ACTH treatment.
      Maximal stimulation of CYP1B1 protein and mRNA by ACTH has been duplicated in
      fasciculata cells by 8-bromo-cAMP and the adenylyl cyclase agonist, forskolin,
      indicating that cAMP mediates this induction. CYP1B1 is similarly stimulated by
      ACTH in rat adrenal glomerulosa cells, although constitutive expression of CYP1B1
      is about 4-fold lower. Angiotensin II treatment of glomerulosa cells, which
      stimulated aldosterone synthesis 3-fold, had no effect on CYP1B1 activity or
      expression. Treatment of fasciculata and glomerulosa cells with 2,3,7,8
      tetrachlorodibenzo-p-dioxin resulted in small increases in CYP1B1 activity (1.8-
      and 2.5-fold, respectively), but much larger increases (5- and 6-fold,
      respectively) in CYP1B1 at the mRNA level 2,3,7,8-Tetrachlorodibenzo-p-dioxin had
      no effect in the presence of ACTH stimulation. CYP1B1 is not coordinately
      expressed with steroidogenic enzymes. CYP11A1 and CYP21 mRNAs are far more
      responsive to ACTH, in part because of lower basal expression. CYP1B1 exhibited a
      transient response to ACTH that peaked (9-fold) at 6 h before declining to about
      4-fold at 36 h, the time when CYP21 mRNA was maximally stimulated. The complete
      inactivation of CYP1B1 activity in fasciculata cells by a mechanism-based
      inhibitor, 1-ethynylpyrene, did not affect corticosterone production, indicating
      that this protein does not have a direct physiological role in the steroidogenic
      response.

PMID- 7588247
TI  - Differentiation of bovine preovulatory follicles during the follicular phase is
      associated with increases in messenger ribonucleic acid for cytochrome P450 side
      chain cleavage, 3 beta-hydroxysteroid dehydrogenase, and P450 17 alpha
      hydroxylase, but not P450 aromatase.
AB  - In cattle, a dramatic increase in plasma estradiol occurs during the short 2- to
      3-day follicular phase. The objective of this study was to investigate the
      molecular mechanisms that mediate this critical change, specifically whether
      increases in the steroidogenic ability of granulosa and thecal cells of the
      preovulatory follicle are associated with increases in the levels of messenger
      RNA (mRNA) for steroidogenic enzymes. Luteolysis and a follicular phase were
      induced cycling Holstein heifers (n=15) by injection of a luteolytic dose of
      prostaglandin F2 alpha (PGF 2 alpha) on day 6 or 7 of the estrous cycle (day 0 =
      estrus), and preovulatory follicles were obtained at three stages of
      differentiation (0, 12, or 24 h post-PGF2 alpha treatment). To assess
      developmental changes in steroidogenesis in vivo, estradiol and androstenedione
      were measured in follicular fluid and in culture medium after a 3-h incubation of
      granulosa and thecal cells in defined medium with or without gonadotropins. To
      determine whether changes in mRNA for steroidogenic enzymes are associated with
      changes in follicular steroidogenesis, levels of mRNA for cytochrome P450 side
      chain cleavage (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta HSD),
      cytochrome P450 17 alpha-hydroxylase, and cytochrome P450 aromatase (P450arom)
      were measured in thecal and granulosa cells using ribonuclease protection assays.
      Concentrations of estradiol in follicular fluid were relatively high at time
      zero, increased significantly by 12 h, and increased further by 24 h post-PGF2
      alpha treatment. However, the aromatizing activity of granulosa cells was high at
      the time of PGF2 alpha injection and did not increase significantly during the
      first 24 h after the initiation of luteolysis. The aromatizing activity of
      granulosa cells was reflected in levels of mRNA for P450arom, which was
      relatively abundant in granulosa cells obtained before luteolysis and did not
      increase further during the first 24 h of the follicular phase. Concentrations of
      androstenedione were virtually undetectable in follicular fluid at time zero and
      had increased dramatically by 12 and 24 h post-PGF2 alpha treatment. Similarly,
      thecal cells isolated at 24 h secreted 3-fold more androstenedione than cells
      isolated at the time of PGF2 alpha injection. Androstenedione production by
      thecal cells in response to LH was also markedly higher at 12 and 24 h than at
      the time of PGF2 alpha injection. Likewise; levels of mRNA for P450 17 alpha
      hydroxylase increased significantly by 12 h post-PGF2 alpha treatment.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7588249
TI  - Thrombospondins selectively activate one of the two latent forms of transforming
      growth factor-beta present in adrenocortical cell-conditioned medium.
AB  - Transforming growth factor-beta (TGF beta) has been shown previously to be a
      potent inhibitor of bovine adrenocortical cell steroidogenic functions. However,
      it is present in the culture medium of these cells in a latent form. In this
      study, we analyzed in detail the biochemical composition of this latent TGF beta.
      Two distinct complexes could be separated chromatographically by gel filtration
      on Sephacryl S-300, and their composition was studied using immunochemical
      methods. The results indicate that one form (peak I) is a complex between alpha 2
      macroglobulin (alpha 2M) and either the unprocessed TGF beta precursor or the
      mature form of TGF beta. In a major fraction of this complex, TGF beta is
      covalently linked to alpha 2 M, whereas in a minor fraction, it is noncovalently
      bound and, therefore, activatable. The second form of latent TGF beta (peak II)
      is a complex among latent TGF beta-binding protein (LTBP), latency-associated
      protein, and mature TGF beta and a complex between LTBP and unprocessed TGF beta.
      We investigated the ability of thrombospondins (TSP1 and TSP2) to activate these
      latent forms of TGF beta. TSP1 and TSP2 were equally potent at activating the
      LTBP-latency-associated protein-TGF beta complex in the absence of cell contact,
      but were ineffective on the alpha 2M-TGF beta complex. Therefore, TGF beta may
      act as an autocrine regulator of adrenocortical steroidogenic functions. Its
      activity appears to be controlled by TSPs, the local production of which is
      regulated by systemic ACTH.

PMID- 7588248
TI  - Regulation of porcine granulosa cell 3-hydroxy-3-methylglutaryl coenzyme A
      reductase by insulin and insulin-like growth factor I: synergism with follicle
      stimulating hormone or protein kinase A agonist.
AB  - In species such as the pig and human, gonadal steroidogenesis is believed to be
      dependent upon the availability of low density lipoprotein (LDL) cholesterol.
      However, before ovulation, Graafian follicles are impermeant to lipoproteins in
      the LDL class. Thus, de novo cholesterol biosynthesis via the rate-determining
      enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is likely to
      provide a significant mechanism for generating sterol substrate for
      steroidogenesis by granulosa cells before follicular rupture. As serum-free
      monolayer culture of (swine) granulosa cells offers an in vitro model of
      hormonally responsive HMG-CoA reductase, we generated a (porcine) complementary
      DNA and homologous complementary RNA to investigate by sensitive and specific
      ribonuclease protection assay the hormonal regulation of HMG-CoA reductase gene
      expression in ovarian cells from immature Graafian follicles. Using reverse
      transcriptase-polymerase chain reaction, we cloned and sequenced a 238-base pair
      complementary DNA from porcine luteal tissue that encodes the catalytic region of
      HMG-CoA reductase. GenBank analysis of the DNA sequence homology between the pig
      and other species showed the greatest concordance with human (88%) and hamster
      (90%). Solution hybridization/ribonuclease protection analysis of total RNA
      isolated from serum-free monolayer cultures of porcine granulosa cells revealed
      that insulin (3 micrograms/ml) increased HMG-CoA messenger RNA (mRNA)
      concentrations corrected for constitutive 18S ribosomal RNA expression in a time
      dependent fashion, with significant effects observed at 12 h and a 6-fold
      increase by 48 h. Recombinant human insulin-like growth factor I (IGF-I) peptide
      was able to mimic the action of insulin alone. Neither FSH (100 ng/ml) nor 8
      bromo-cAMP (1 mM) had observable effects on HMG-CoA message accumulation at any
      time point studied. However, the combined action of either FSH and insulin or 8
      bromo-cAMP and insulin resulted in synergistic increases in reductase mRNA by 31-
      and 17-fold, respectively. To assess the possible feedback effects of sterol on
      HMG-CoA gene expression, granulosa cells were treated with LDL. At physiological
      concentrations, LDL suppressed basal expression of HMG-CoA mRNA to levels below
      the control value. In addition, LDL inhibited insulin-stimulated HMG-CoA mRNA
      accumulation by 84% as well as the synergistic effects of insulin and FSH (by
      94%) and of insulin and 8-bromo-cAMP (by 93%). We conclude that insulin alone or
      in combination with FSH or cAMP augments the accumulation of HMG-CoA reductase
      mRNA in ovarian (granulosa) cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588250
TI  - Intermittent parathyroid hormone treatment increases osteoblast number, steady
      state messenger ribonucleic acid levels for osteocalcin, and bone formation in
      tibial metaphysis of hypophysectomized female rats.
AB  - The effects of GH and PTH on cancellous histomorphometry were determined in the
      proximal tibial metaphysis of hypophysectomized (HYPOX) sexually mature female
      rats. HYPOX resulted in uterine atrophy and a loss in body weight. Longitudinal
      bone growth ceased and bone formation was greatly reduced. There were decreases
      in cancellous bone area, trabecular number, and trabecular thickness.
      Intermittent treatment with GH did not influence uterine weight in HYPOX rats.
      However, GH resulted in resumption of whole body weight gain, as well as
      maintenance of normal longitudinal bone growth. Additionally, GH partially
      maintained bone formation in HY POX rats and did not have a significant effect on
      steady state messenger RNA levels for osteocalcin. Intermittent treatment with
      PTH had no effect on whole body weight gain, uterine weight, or longitudinal bone
      growth. In contrast, PTH increased bone formation compared with the baseline,
      HYPOX, and GH-treated HYPOX rats, and dramatically increased osteocalcin
      messenger RNA levels compared with the latter two groups. The increased bone
      formation was primarily due to an increase in osteoblast number; the mineral
      apposition rate, an index of osteoblast activity, was increased compared with
      control and GH-treated rats but not compared with baseline values. Interestingly,
      neither treatment influenced indices of bone resorption.

PMID- 7588251
TI  - Regulation of oxytocin receptor messenger ribonucleic acid in the ventromedial
      hypothalamus by testosterone and its metabolites.
AB  - Oxytocin receptor (OR) binding in the ventromedial hypothalamus (VMH) is
      regulated by testosterone (T) and its metabolites, estrogen (E2) and
      dihydrotestosterone (DHT). Previous studies have reported that OR binding
      increases in the VMH in castrated male rats when they are replaced with T or E2
      compared to that in vehicle-treated animals. DHT alone had no effect on OR
      binding, but when given in combination with E2 appeared to have a synergistic
      effect. This study was designed to determine whether these effects of steroid
      hormones on OR binding in the VMH are associated with changes in OR messenger RNA
      (mRNA) expression. Male rats were castrated or sham operated and given T
      propionate (TP), E2 benzoate (EB), DHT plus EB, or an oil vehicle. OR mRNA was
      assessed using a rat complementary RNA OR probe and in situ hybridization
      techniques. OR binding to tissue slices was quantified autoradiographically using
      an OR antagonist, [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin.
      These experiments showed that TP and EB increased both OR mRNA and OR binding in
      the VMH significantly above levels in vehicle-treated animals. However, animals
      given both EB and DHT exhibited significantly lower OR mRNA expression and OR
      binding in the VMH compared to those in animals treated with TP or EB alone.
      These data indicate that increases in VMH OR binding in response to gonadal
      steroids are accompanied by changes at the mRNA level that correspond well in
      magnitude and direction with those in the OR-binding sites.

PMID- 7588252
TI  - The effect of naloxone administration on the secretion of corticotropin-releasing
      hormone, arginine vasopressin, and adrenocorticotropin in unperturbed horses.
AB  - We used our nonsurgical method for collecting equine pituitary venous blood to
      study the role of endogenous opioids in the basal regulation of the hypothalamo
      pituitary-adrenal axis. We gave mares the opioid antagonist, naloxone (NAL), at
      either a high (0.5 mg/kg i.v. bolus, followed by infusion of 0.25 mg/kg.h; n = 4)
      or low (0.2 mg/kg i.v. bolus; n = 6) dose rate. Pituitary venous blood was
      collected continuously, divided into 0.5- or 1-min segments for 15-30 min before
      and 1 h after the NAL bolus, and assayed for CRH, arginine vasopressin (AVP), and
      ACTH. The mares tolerated NAL administration well, with little difference between
      dose rates in the mild transient side-effects. Both NAL doses increased jugular
      cortisol concentrations (high, P = 0.0022; low, P = 0.0001) and the ACTH
      secretion rate (high, P = 0.0056; low, P = 0.0103). High dose NAL raised the
      secretion rates of AVP (P = 0.0252) and CRH (P = 0.0106); however, the magnitude
      of ACTH responses exceeded those in AVP and CRH, as shown by increased ratios
      between ACTH and AVP (P = 0.0246) or CRH (P = 0.0122) secretion rates. After low
      dose NAL, neither CRH nor AVP secretion was altered. Indeed, CRH declined as ACTH
      rose in 4 mares and was unchanged in a fifth mare. When data from the 10 mares
      were pooled, mean secretion rates of ACTH and CRH were correlated after (P <
      0.05), but not before, NAL treatment. Overall, mean ACTH and AVP secretion rates
      were not correlated during any 30-min period, but in individual mares, minute to
      minute AVP and ACTH secretion patterns were always correlated. We conclude that
      endogenous opioids inhibit the equine hypothalamo-pituitary-adrenal axis under
      basal conditions; however, their sites of action do not appear to lie solely on
      CRH and/or AVP neurons. It seems likely that endogenous opioids also inhibit the
      release of a third ACTH secretagogue or promote the secretion of an ACTH release
      inhibitory factor.

PMID- 7588253
TI  - A comparison of rat small intestinal insulin and insulin-like growth factor I
      receptors during fasting and refeeding.
AB  - Insulin-like growth factor I (IGF-I) and insulin may be important regulators of
      intestinal growth. To investigate small intestinal IGF-I receptors (IGF-IR) and
      insulin receptors (IR) during intestinal cell atrophy and regeneration, we
      compared indexes of IGF-IR and IR expression in rat jejunum after 72 h of fasting
      and 24-72 h of enteral refeeding. Fasting induced intestinal atrophy, reduced
      plasma insulin and IGF-I concentrations, and markedly decreased jejunal IGF-I
      messenger RNA (mRNA) levels; these changes were reversed by refeeding. Fasting
      significantly increased jejunal specific insulin binding, IR content (to 230% of
      the fed control value), and the 9.6- and 7.4-kilobase IR mRNA transcript levels
      (to 202% and 218% of control values, respectively). These IR indexes rapidly
      decreased to control levels with refeeding. Levels of IGF-IR (by Scatchard
      analysis) and IGF-I-R mRNA were not significantly altered with fasting. The 11
      kilobase IGF-IR mRNA transcript increased significantly during the first 24 h of
      refeeding (to 166% of the control value), and IGF-IR number rose 3-fold. We
      conclude that rat jejunal IR and IGF-IR are differentially regulated by nutrient
      availability. Up-regulation of jejunal IGF-I and IGF-IR expression during
      refeeding suggests a role for the IGF action pathway in gut trophic responses to
      enteral nutrients.

PMID- 7588254
TI  - Pyroglutamyl-phenylalanyl-proline amide attenuates thyrotropin-releasing hormone
      stimulated insulin secretion in perifused rat islets and insulin-secreting clonal
      beta-cell lines.
AB  - TRH immunoreactivity has been detected in the pancreas of man and rat and
      localized to the islets of Langerhans. We studied the effect of synthetic TRH and
      the related tripeptide pyroglutamyl-phenylalanyl-proline amide (EFP) on isolated
      perifused rat islets and the glucose-responsive clonal cell lines HIT-T15 and
      RIN5AH. TRH at 10 nM potentiated [0.5 +/- 0.1 (control) vs. 0.8 +/- 0.1 (TRH)
      pmol/10(6) cells per 120 min; mean +/- SEM; n = 6; P < 0.001; n = 15], whereas
      EFP from 1 nM upwards suppressed glucose-stimulated insulin secretion [0.8 +/-
      0.1 (control) vs. 0.5 +/- 0.1 (EFP) pmol/10(6) cells per 120 min; P < 0.001; n =
      12) in the cell lines. Further, EFP reversed TRH-stimulated insulin release.
      Similar responses were observed in perifused isolated rat islets at the tested
      dose of 1 microM. Gel permeation chromatography of rat adult and neonatal whole
      pancreas, isolated islets, and HIT cell extracts demonstrated the elution of
      total TRH-like immunoreactivity (t-TRH-LI) in the same position as synthetic TRH.
      Cation exchange analysis of the t-TRH-LI from rat adult pancreas and HIT cell
      extracts showed that neutral TRH-like peptides corresponding to synthetic EFP
      were also present. Reverse-phase fast protein liquid chromatographic analysis of
      t-TRH-LI in the unbound fraction of these extracts subjected to anion exchange
      columns, also demonstrated peaks corresponding to synthetic EFP. We conclude that
      TRH potentiates, whereas EFP inhibits, glucose-stimulated insulin release in
      isolated perifused islets and the cell lines. In addition, EFP reversed the
      stimulatory effect of TRH. The presence of EFP-LI in rat adult and neonatal
      pancreas and HIT cell extracts suggests it may contribute in the modulation of
      pancreatic endocrine function.

PMID- 7588255
TI  - Steroid production after in vitro transcription, translation, and mitochondrial
      processing of protein products of complementary deoxyribonucleic acid for
      steroidogenic acute regulatory protein.
AB  - We have previously demonstrated that steroidogenic acute regulatory protein
      (StAR) is essential for the rate-limiting step in the acute regulation of
      steroidogenesis, which is the transport of cholesterol from the outer to the
      inner mitochondrial membrane. We have hypothesized that this transport occurs as
      the 37-kilodalton (kDa) precursor form of StAR is imported into the mitochondria
      and processed to its 30-kDa mature forms. Using an in vitro transcription and
      translation system in the presence of mitochondria isolated from unstimulated
      mouse MA-10 Leydig tumor cells, we now directly show that the 37-kDa form is
      indeed the cytosolic precursor of StAR and can be processed by mitochondria to
      all four 30-kDa mature forms. To determine the subcellular location of StAR in
      steroidogenic cells, ultrastructural immunocytochemistry was performed in adrenal
      zona fasciculata cells using the protein A-gold technique. We show that StAR is
      associated exclusively with the mitochondria. There, StAR is primarily localized
      in the intermembrane space and the intermembrane space side of the cristae
      membrane. StAR was shown to induce steroid production in isolated mitochondria.
      StAR protein was expressed in COS1 cells and the cell lysate, which was shown to
      contain abundant levels of StAR by Western blot analysis, was incubated with
      mitochondria isolated from unstimulated MA-10 cells. In these experiments, StAR
      increased steroid production by at least 4-fold over control mock-transfected
      lysate, and this increase was time and dose dependent. Furthermore, the increase
      in steroid production induced by StAR-containing lysate was not observed when
      COS1 lysate containing high levels of another mitochondrially imported protein,
      adrenodoxin, was used. We conclude from these results that in response to tropic
      hormone stimulation of steroidogenic cells, StAR is synthesized as a 37-kDa
      precursor, imported into the mitochondria, processed to its 30-kDa mature forms,
      and localized to the intermembrane space. During import and processing in vitro,
      StAR induces steroid production in isolated mitochondria in a specific manner.

PMID- 7588256
TI  - Inhibition of luteinizing hormone-releasing hormone secretion by delta-opioid
      agonists in GT1-1 neuronal cells.
AB  - The endogenous opioids play a major role in regulation of the secretion of
      hypothalamic LHRH. However, it is not clear whether opioids exert a direct effect
      on LHRH neurons or interfere with other neuronal systems impinging on the cells
      synthesizing LHRH. The neuronal LHRH-producing cell line GT1 provides a new model
      to evaluate which signals may directly modify LHRH release. In a previous paper
      it has been reported that opioid-binding sites of the delta-type are present in a
      clone of the GT1 cells (GT1-1). In the present study, the possible effects of
      opioids on the release of LHRH were studied in GT1-1 cells. The results obtained
      show that only the addition of opioid agonists that bind to delta-receptors
      brings about a significant inhibition of forskolin- or prostaglandin E2
      stimulated LHRH release in GT1-1 cells. The effect of the delta-opioid agonist [D
      Pen2,D-Pen5]enkephalin is dose dependent and is reversed by the universal opioid
      antagonist naltrexone and the delta-specific antagonist naltrindole. No effect of
      opioid agonists or antagonists was observed in unstimulated cells. These results
      suggest that opioids may control the release of LHRH also, acting directly on
      LHRH-producing neurons.

PMID- 7588258
TI  - Analysis of messenger ribonucleic acid and protein for the ligands and receptors
      of the platelet-derived growth factor signaling pathway in the placenta,
      extraembryonic membranes, and uterus during the latter half of murine gestation.
AB  - Previous investigation of ligand and receptor messenger RNA (mRNA) expression
      implicated the platelet-derived growth factor (PDGF) pathway as a participant in
      the maintenance of pregnancy and fetal development during the first half of
      murine gestation. We extended these studies using Northern and in situ RNA
      hybridization and immunohistochemical detection of protein to evaluate the
      expression kinetics and cell-specific localization of PDGF-A, PDGF-B, PDGF alpha
      receptor, and PDGF beta-receptor in mouse placenta, extraembryonic membranes, and
      uterus during the second half of gestation (days 9.5-18.5). Northern blotting
      experiments reveal that mRNAs for the PDGF signaling components exhibit unique
      time-dependent and tissue-specific expression in the placenta and uterus, being
      progressively and coordinately up-regulated as gestation proceeds. Cell-specific
      localization of mRNA and protein by in situ hybridization and
      immunohistochemistry demonstrates widespread expression in multiple cell types of
      the placenta, gravid uterus, and extraembryonic membranes. Abundant PDGF protein
      and mRNA expression is exhibited in the nucleated fetal erythroid progenitor
      cells that originate in the extraembryonic membranes and circulate throughout the
      developing conceptus. Our data together with those of previous studies
      demonstrate that PDGF ligands and receptors are globally expressed in many cell
      types within fetal and maternal tissues during murine gestation and, thus, imply
      a potential role for PDGF in fetal development and maternal-fetal interactions.

PMID- 7588257
TI  - Regulation of glucagon-like peptide-1-(7-36) amide, peptide YY, and neurotensin
      secretion by neurotransmitters and gut hormones in the isolated vascularly
      perfused rat ileum.
AB  - Neurotensin (NT), peptide YY (PYY), and several peptides derived from proglucagon
      are promptly released from endocrine cells of the distal part of the gut after
      oral ingestion of a meal, thus suggesting that release of these peptides is
      partly under neural and/or hormonal control. Our previous studies conducted with
      a model of isolated vascularly perfused rat colon showed that colonic L cells are
      highly responsive to several transmitters of the gut and to the hormonal peptide
      GIP. To test the possibility that hormones produced by the proximal small
      intestine or transmitters of the enteric nervous system may also modulate the
      secretory activity of the ileal L cells, various intestinal regulatory peptides
      and neurotransmitters were administered intraarterially for 30 min in the
      isolated vascularly perfused rat ileum preparation. The secretory activity of the
      ileal N cells was comparatively assessed. The release of NT, PYY, and glucagon
      like peptide-1 (GLP-1) in the portal effluent was measured with specific RIAs.
      The muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M
      provoked a biphasic release of PYY, GLP-1, and NT, consisting of an early peak
      followed by a sustained response. Similarly, bombesin (10(-7) M) induced a marked
      biphasic release of PYY and GLP-1. In contrast, the NT response was essentially
      monophasic, characterized by an early peak secretion. Tetrodotoxin did not modify
      the bombesin-induced release of PYY, GLP-1, and NT. The beta-adrenergic agonist
      isoproterenol at a concentration of 10(-6) M induced a transient rise in portal
      PYY and GLP-1 concentrations, whereas the effect on NT release was clearly
      biphasic. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise
      in PYY, GLP-1, and NT immunoreactivities in the portal effluent (peaks at 600%,
      500%, and 550% of the basal values, respectively, 4 mi n after the start of
      infusion). Intraarterial infusion of GIP over the concentration range (0.5-3 nM)
      evoked a significant increase in portal concentration of the three peptides only
      at the threshold concentration of 3 nM. Secretin (50 pM) or cholecystokinin (50
      pM) did not affect the release of ileal hormones. In conclusion, ileal L and N
      cells respond to a variety of transmitters of the gut. The pattern of peptide
      release depends on the cell type studied. The two cosynthesized peptides, PYY and
      GLP-1, appear to be cosecreted in the conditions of the present study.

PMID- 7588261
TI  - Widespread distribution of somatostatin receptor messenger ribonucleic acids in
      rat pituitary.
AB  - The expression of five somatostatin receptor subtypes, rsstr1-5, was examined in
      rat pituitary by in situ hybridization histochemistry. The anterior lobe of the
      pituitary expressed mRNA encoding all five rsstr subtypes. Relatively high levels
      of rsstr3 mRNA expression were also observed in the intermediate lobe of the
      pituitary. If all five rsstr proteins are expressed in the pituitary, the effects
      of somatostatin and somatostatin-28 on pituitary function may therefore represent
      the composite activation of more than one sstr. Co-localization studies on the
      same pituitary sections revealed a widespread distribution of rsstr mRNA in the
      major endocrine cell groups. Somatotrophs showed a relatively high level of
      rsstr4 and -5 mRNA expression while thyrotrophs predominantly expressed rsstr2
      mRNA. These data may point to the potential roles for sstr subtypes in mediating
      SRIF physiology in the pituitary.

PMID- 7588262
TI  - Rapid desensitization of GnRH-stimulated intracellular signalling events in alpha
      T3-1 and HEK-293 cells expressing the GnRH receptor.
AB  - The gonadotropin-releasing hormone receptor (GnRH-R) desensitizes following
      chronic exposure to GnRH or its agonists. However, it is not certain whether the
      GnRH-R undergoes rapid homologous desensitization analogous to other members of
      the G-protein coupled receptor (GPCR) superfamily. This study investigated rapid
      desensitization events in two cell lines expressing the GnRH-R; (the pituitary
      gonadotrope alpha T3-1 cell line and the stably transfected human embryonal
      kidney cells, HEK-293). In both cell types, total inositol phosphate (IP)
      production did not desensitize, increasing linearly over 10 min. Short-term GnRH
      pretreatment also did not desensitize the rapid phase ( < or = sec) of the early
      Ins1,4,5P3 response despite a partial desensitization of the plateau phase ( > 1
      min). It is likely that Ins1,4,5P3 metabolism rather than desensitization is
      responsible for this partial effect. In contrast, GnRH-stimulated calcium
      responses did desensitize in a dose-dependent fashion in both alpha T3-1 and HEK
      293 cells expressing the GnRH-R. These results suggest that rapid GnRH-R
      desensitization occurs at a level beyond both the receptor and phospholipase C
      (PLC) activation. These events were receptor specific and not related to cell
      type, since similar rapid desensitization profiles were observed in both GnRH-R
      expressing pituitary and nonpituitary cell types. In contrast, profiles of GnRH
      stimulated calcium responses were cell type specific.

PMID- 7588260
TI  - Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous
      system.
AB  - Neurosteroids are steroids that are synthesized de novo in the brain and include
      some classical (adrenal and gonadal steroids) and some unique brain-specific
      steroids. Neurosteroids are thought to mediate their action through ion gated
      channel receptors such as gamma-aminobutyric acid(A) and N-methyl-D-aspartate
      rather than through classical nuclear steroid hormone receptors. Some enzymes
      involved in neurosteroidogenesis have been identified as those found in
      steroidogenic tissues, and some may be unique to the brain. We previously
      demonstrated that the messenger RNAs (mRNA) for the cholesterol side-chain
      cleavage enzyme, cytochrome P450scc, and one form of 11 beta-hydroxylase,
      cytochrome P450c11 beta, are regionally expressed in the adult rat brain.
      However, cytochrome P450c17, which has 17-hydroxylase and 17,20-lyase activity
      and is thought to be required for the synthesis of dehydroepiandrosterone, was
      not detected in any region of the rat brain, even though dehydroepiandrosterone
      is one of the most abundant neuroactive steroids. We now demonstrate that P450c17
      is expressed in the nervous system of the developing rodent embryo. By
      ribonuclease protection assays, P450c17 mRNA was found in the trunk but not in
      the head of rat embryos but reverse transcriptase-polymerase chain reaction
      analysis showed expression of P450c17 mRNA in the head of E15.5 to E19.5 rat
      embryos. Immunocytochemically detectable P450c17 protein was expressed in the
      nervous system as early as embryonic day E10.5 in the mouse, mainly in tissue
      derived from the neural crest. Neuronal cell bodies as well as fibers staining
      for P450c17 were observed in the central and peripheral nervous systems. The
      sites of P450c17 expression in the peripheral nervous system suggest it may be
      involved in a wide variety of sensory-motor functions. In the central nervous
      system, cell bodies expressing P450c17 are found in the hind brain, in
      mesencephalic nuclei, and in a region in the location of the locus coeruleus, but
      in cells distinct from those expressing the dopamine-beta-hydroxylase.
      Furthermore, its particular location and temporal expression in axons reaching
      the cortical areas suggest it is a marker for the axonal growth in this region,
      and that its neurosteroid product may be a signal for targeting cortical axons
      during embryogenesis.

PMID- 7588259
TI  - Calcitonin-secreting cells of the thyroid express an extracellular calcium
      receptor gene.
AB  - Calcitonin (CT) secretion by parafollicular cells of the thyroid (C cells) is
      regulated by small changes in the concentration of extracellular calcium
      ([Ca2+]e). Elevation of [Ca2+]e elicits a rise in the C cell cytoplasmic calcium
      concentration and stimulates CT release. The molecular entity through which C
      cells detect changes in [Ca2+]e and modulate hormone secretion is unknown.
      Recently, an extracellular calcium-sensing receptor (CaR) complementary DNA was
      isolated from bovine parathyroid gland. To assess whether parathyroid cells and C
      cells use similar mechanisms to detect changes in ambient Ca2+, rat, human, and
      sheep C cells were examined for expression of the parathyroid CaR or a related
      receptor isoform. Reverse transcription-polymerase chain reaction analysis
      identified CaR transcripts in rat and human thyroid gland. Northern blot analysis
      demonstrated CaR messenger RNA (mRNA) in rat thyroid gland, a human medullary
      thyroid carcinoma (MTC) isolate, and a highly enriched preparation of sheep C
      cells. Rat MTC 44-2 cells, a cell line responsive to changes in [Ca2+]e, express
      abundant levels of CaR mRNA. Human TT cells, a C cell line lacking the
      extracellular calcium-sensing function, have undetectable levels of CaR mRNA by
      Northern blot analysis. Western blot analysis, using antiserum specific to the
      parathyroid CaR, detected CaR protein in rMTC 44-2, but not TT cells.
      Immunostaining of both dispersed sheep C cells and rat thyroid gland sections
      identified C cell-specific expression of the CaR protein, and in situ
      hybridization analysis confirmed the C cell-specific expression of CaR mRNA in
      the intact rat thyroid. The nucleotide sequence of the coding region of the rMTC
      44-2 CaR transcripts was found to encode the same CaR protein as that expressed
      in the parathyroid and kidney. The results demonstrate that C cells express the
      same extracellular calcium-sensing receptor that is found in parathyroid and
      kidney, and the presence of this receptor protein in C cell lines correlates with
      the extracellular calcium-sensing function. This CaR is likely to represent the
      primary molecular entity through which C cells detect changes in [Ca2+]e and
      control CT release, suggesting that activation of the same receptor can either
      stimulate or inhibit hormone secretion in different cell types.

PMID- 7588263
TI  - Expression of mRNA for somatostatin receptor (sstr) types 2 and 5 in individual
      rat pituitary cells. A double labeling in situ hybridization analysis.
AB  - To characterize cell specific expression of sstr subtypes in the pituitary we
      have analyzed mRNA for sstr1-5 in rat pituitary somatotrophs by reverse
      transcriptase polymerase chain reaction and determined the pattern and level of
      expression of mRNA for sstr subtypes 2 and 5 in individual pituitary cell
      subpopulations by double label in situ hybridization. Purified somatotrophs
      expressed mRNA for all 5 sstrs. In situ hybridization analysis revealed sstr5
      mRNA in 70% of somatotrophs, 57% of thyrotrophs, 38% of corticotrophs, 33% of
      lactotrophs, and 21% of gonadotrophs. mRNA for sstr2 occurred in 40% of
      somatotrophs, 36% of thyrotrophs, 26% of lactotrophs, 3% of corticotrophs, and 8%
      of gonadotrophs. Not only were more cells positive for sstr5 mRNA but the average
      number of autoradiographic grains/cell was also higher for sstr5 than sstr2.
      These results show expression of multiple sstr genes in individual pituitary
      cells. mRNA for sstr2 and 5 occur in each of the 5 major pituitary cell subsets,
      sstr5 mRNA being more widely and more abundantly expressed than sstr2.

PMID- 7588267
TI  - Prolactin, proliferation, and protooncogenes.

PMID- 7588268
TI  - Rapid induction of pim-1 expression by prolactin and interleukin-2 in rat Nb2
      lymphoma cells.
AB  - The lactogen-dependent Nb2 lymphoma line (Nb2-11) represents a useful pre-T cell
      model for investigation of early molecular events coupled to PRL-stimulated cell
      cycle progression. Expression of pim-1, a protooncogene that encodes a conserved
      cytosolic serine/threonine protein kinase, is rapidly induced in hematopoietic
      cells upon mitogen stimulation and is thought to be important for lymphocyte
      activation. The present study was conducted to determine whether mitogen
      stimulation in Nb2-11 or lactogen-independent Nb2-SFJCD1 cells provokes pim-1
      gene expression. The pim-1 transcript was undetectable in control growth-arrested
      Nb2-11 cultures; however, PRL rapidly stimulated its expression in a biphasic
      manner. Peak expression occurred within 2-4 h (> 40-fold) and was followed by a
      second elevation at 12 h. The effect of PRL and IL-2 to induce pim-1 at 2 h was
      concentration dependent and not inhibited by cycloheximide. In Nb2-SFJCD1 cells,
      pim-1 messenger RNA was expressed in control cultures and augmented by PRL
      stimulation. Results from stability studies indicated that the t1/2 values for
      the pim-1 transcript were 79 and 81 min in PRL-stimulated Nb2-11 cells at 2 and
      12 h. However, in the lactogen-treated Nb2-SFJCD1 line, it was nearly 3-fold more
      stable (219 min) at 2 h compared to that determined at either 12 h or in
      unstimulated cultures. In other experiments, PRL-stimulated expression of the pim
      1 protein was evaluated in [35S]methionine-labeled cells by immunoprecipitation
      and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In Nb2-11 cells,
      enhanced [35S]pim-1 expression paralleled its messenger RNA transcription through
      8 h. Elevated [35S]pim-1 was detected within 1 h and peaked by 2-4 h. Therefore,
      pim-1 represents an immediate early gene induced by PRL stimulation in Nb2-11
      cells. Its initial peak of transcription occurs early during G1 cell cycle
      progression, whereas a second elevation is coincident with the G1/S transition.
      These results demonstrate that mitogen-induced expression of pim-1 is a rapid
      event in Nb2 lymphoma cells and suggest that it may be associated with cell cycle
      progression.

PMID- 7588265
TI  - Coordinated effects of insulin-like growth factor I on inhibitory pathways of
      cell cycle progression in cultured cardiac muscle cells.
AB  - Insulin-like growth factor I (IGF I) plays a key role in the regulation of cell
      proliferation. Progression of the cell cycle is regulated by stimulatory and
      inhibitory pathways. In order to understand the mechanisms through which IGF I
      regulates cardiac muscle growth, we have studied the effects of IGF I on
      inhibitory pathways involving p53 and WAF1 in cultured cardiac muscle cell line
      H9C2. The onset of DNA synthesis in response to IGF I stimulation was preceded by
      activation of p53 expression. In addition, IGF I increased p53-dependent and p53
      independent induction of WAF1 in H9C2 cells. Dose-response studies showed that
      IGF I effects on p53-dependent and p53-independent induction of WAF1 occur at
      physiological concentrations of IGF I. These data indicate that IGF I
      coordinately regulates inhibitory pathways of cell cycle progression, and that
      p53-dependent and p53-independent induction of WAF1 may provide negative control
      mechanisms to regulate stimulatory pathways of cell cycle progression activated
      by IGF I.

PMID- 7588264
TI  - A member of the CTF/NF-1 transcription factor family regulates murine growth
      hormone receptor gene promoter activity.
AB  - Deletional analysis by transient transfection of COS-7 cells with the murine
      growth hormone (GH) receptor gene promoter for the L1 transcript identified a 16
      bp enhancer element located approximately 3.0 kb upstream of the major
      transcription start sites. The sequence of this enhancer element suggested a
      binding motif for the CTF/NF-1 family of transcription factors. In
      electromobility shift assays (EMSA) this DNA-element formed a sequence-specific
      complex with nuclear proteins from COS-7 cells. Competition experiments with
      oligonucleotide containing a consensus binding motif for CTF/NF-1 protein(s) and
      supershift EMSA with an anti-CTF/NF-1 antibody established that a CTF/NF-1 like
      protein binds to this enhancer element.

PMID- 7588269
TI  - D2-like dopamine receptor mediates dopaminergic or gamma-aminobutyric acidergic
      inhibition of melanotropin-releasing hormone release from the pars intermedia in
      frogs (Rana nigromaculata).
AB  - Frogs can adapt to their background by making their skin color lighter or darker
      as necessary, and this adaptation is regulated by MSH. We investigated the
      mechanism inhibiting MSH release from the pars intermedia (PI) of the pituitary
      gland in frogs (Rana nigromaculata) by ultrastructural immunohistochemistry and
      bioassay using the melanophore index. The PI contained fibers immunoreactive for
      tyrosine hydroxylase, gamma-aminobutyric acid (GABA), and neuropeptide Y, which
      made synaptic contacts with MSH cells. The synapses had an asymmetric profile
      with small round and large-cored synaptic vesicles. The skin of frogs adapted to
      a white background became darker after administration of 6-hydroxydopamine or
      autografting of the PI into the anterior chamber of the eye. The skin of
      autografted frogs became lighter after the administration of dopamine or GABA
      into the anterior chamber. Lightening of skin color with dopamine was inhibited
      by a D2 receptor antagonist (sulpiride), and the effect of GABA was blocked by
      both sulpiride and a GABAA receptor antagonist (bicuculline). These results
      indicate that MSH release from the PI in frogs may be inhibited by dopaminergic
      nerves via the D2-like receptor and by GABAergic nerves via the D2-like and GABAA
      receptors.

PMID- 7588266
TI  - Osteoclast radical interactions: NADPH causes pulsatile release of NO and
      stimulates superoxide production.
AB  - Osteoclasts have been shown to destroy calcified tissue by complex developmental
      steps involving cell recruitment, cell attachment and deployment of multiple
      enzymes. They also appear to regulate resorption by several mechanisms. In
      particular, earlier investigations have indicated that oxygen radical metabolites
      may be produce by osteoclasts. These labile reactants could accelerate
      destruction of calcified tissue. In addition, recent studies have suggested that
      nitric oxide may have an inhibitory role in bone resorption. Previous studies of
      these radical substituents have predicted that interactions of nitric oxide and
      oxygen radicals could explain the conflicting roles of these radicals in the
      control of bone resorption. In view of the requirement of both of the enzymes,
      NADPH-oxidase and NO synthase (NOS), for NADPH(beta-nicotinamide adenine
      dinucleotide phosphate), one level of interaction could be related to competition
      for this necessary cofactor. To test this hypothesis, we have investigated the
      ability of the osteoclast to generate nitric oxide and oxygen radicals after
      stimulation by NADPH. Consistent with earlier diaphorase histochemistry, we have
      shown that resorbing osteoclasts produce NO. Addition of NADPH (10 microM)
      resulted in a transient burst of NO production (measured by porphyrin coated
      microsensor) with an amplitude of 152 +/- 43 nM and a duration of 4 seconds.
      Repetitive stimulation resulted in a decremental response with a partial recovery
      after 30 minutes. Addition of L-NAME (N omega-nitro-L-arginine methyl ester, 100
      microM) to the cells resulted in at least 50% inhibition of the amplitude of NO
      peak and produced an extended peak duration. To compare the effect of the added
      NADPH on superoxide production by osteoclast NADPH-oxidase, osteoclast oxygen
      radicals were detected by EPR(electron paramagnetic resonance) spectrometer with
      the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The production of a spin
      adduct with a quadruplet signal was inhibited by SOD (superoxide dismutase). We
      were not able to demonstrate an increase in superoxide production after addition
      of L-NAME, another possible interaction of NOS and NADPH-oxidase. These results
      demonstrate that although osteoclasts produce both NO and superoxide, NOS
      competition for NADPH is not a major site of interaction with NADPH-oxidase under
      these conditions. Additionally, these initial findings set the stage for the
      further investigation of interactions of osteoclast radicals in modulating bone
      resorption.

PMID- 7588270
TI  - Localization of messenger ribonucleic acids for insulin-like growth factor I (IGF
      I), IGF-II, and the type 1 IGF receptor in the ovine ovary throughout the estrous
      cycle.
AB  - The distribution pattern of messenger RNAs (mRNAs) for insulin-like growth factor
      I (IGF-I), IGF-II, and the type 1 IGF receptor and the detection of IGF-binding
      sites in sections of ovine ovary were demonstrated using in situ hybridization
      and autoradiography. Ovaries were collected from 30 ewes at time points
      throughout the estrous cycle. Luteal IGF-II mRNA and IGF-binding site
      concentrations altered significantly during the cycle, peaking on day 8
      (midluteal phase; P < 0.01) and day 15 (late luteal phase; P < 0.001),
      respectively. In contrast, mRNA expression for IGF-I and the type 1 IGF receptor
      in the corpus luteum was low and did not vary. IGF-binding sites and mRNAs for
      IGF-II and the type 1 IGF receptor were also present at low and constant
      concentrations in ovarian stroma. There was no detectable follicular expression
      of IGF-I mRNA, although there were high concentrations of IGF-II and the type 1
      IGF receptor mRNAs, which both varied significantly with follicular size (P <
      0.001 and 0.01, respectively), with the highest concentrations in small follicles
      (< 2 mm in diameter). Follicular IGF-II expression was confined to the theca,
      whereas the type 1 IGF receptor was present in both theca and granulosa. IGF
      binding site concentrations were significantly higher (P < 0.01) in atretic than
      healthy follicles, but were uninfluenced by follicular size. These results
      suggest that IGF-II, in contrast to IGF-I, appears to be the most significant IGF
      in luteal and, particularly, follicular development in the ewe.

PMID- 7588271
TI  - Conversion of angiotensin II into active fragments by an endosomal pathway in
      bovine adrenal medullary cells in primary culture.
AB  - We previously demonstrated that angiotensin II (AII) is internalized in primary
      cultures of bovine adrenal medullary cells by receptor-mediated endocytosis. In
      the present work, we followed internalized AII in these cells by means of
      confocal laser scanning microscopy combined with analytical subcellular
      fractionation techniques and compared its fate with that of transferrin and
      horseradish peroxidase. The integrity of [125I]AII was investigated by
      chromatography. With pulse-chase experiments, internalized AII could only be
      detected in endosomes using either fluorescence microscopy or fractionation
      studies. With chase, most of the radioactivity initially associated with the
      cells was rapidly released into the medium, as converted fragments (> 60%),
      essentially as AIV (80% of the fragments). Fragments efficiently bound to bovine
      adrenal medullary and cortical cells, a binding that was specifically displaced
      by AIV > AIII = AII. These results indicate that AII is taken up in bovine
      adrenal medullary cells and can be rapidly converted in the endosomal pathway
      into fragments that bind specifically to putative angiotensin receptors. These
      fragments are presumably biologically active and could act on either the
      chromaffin cell itself (autocrine) or the cortical cells (paracrine).

PMID- 7588273
TI  - Identification by mutation of the tyrosine residues in the insulin receptor
      substrate-1 affecting association with the tyrosine phosphatase 2C and
      phosphatidylinositol 3-kinase.
AB  - The insulin receptor substrate-1 (IRS-1) is rapidly phosphorylated on several
      tyrosine residues by the activated insulin receptor. Phosphorylated IRS-1 acts as
      a docking protein for Src homology-2 (SH2) domain-containing proteins involved in
      insulin signaling. These include in vivo the regulatory subunit p85 of the
      phosphatidylinositol 3-kinase (PI3-K) and the phosphotyrosine phosphatase-2C
      (PTP2C). In this report, we examined which tyrosine residues of IRS-1 are
      required for the interactions of IRS-1 with PI3-K and PTP2C. To address this
      issue, we constructed different rat IRS-1 mutants containing mutations in the
      tyrosine residues that interact with the SH2 domains of PI3-K and PTP2C in vitro.
      Each of the IRS-1 mutants obtained have been transiently expressed in 293 EBNA
      cells to study their ability to interact with PI3-K and PTP2C in vivo. Our
      results demonstrate that mutation of tyrosine 608 affects the PI3-K activity
      associated with IRS-1, suggesting that this tyrosine is likely to be a principal
      site of interaction with the SH2 domains of p85 in response to insulin.
      Furthermore, we found that mutation of tyrosines 1172 and 1222 totally prevents
      the insulin-induced association of IRS-1 with the SH2 domains of PTP2C,
      demonstrating that both tyrosines 1172 and 1222 are key elements in the binding
      sites for the SH2 domains of PTP2C. Finally, we found that the ability of
      purified PTP2C to dephosphorylate IRS-1 is dependent on the association of PTP2C
      with phosphorylated IRS-1.

PMID- 7588272
TI  - Expression of nitric oxide synthase isoforms in the thyroid gland: evidence for a
      role of nitric oxide in vascular control during goiter formation.
AB  - The thyroid gland is a highly vascular tissue, and its blood flow changes
      dramatically in various pathological conditions. Although the mechanisms
      regulating these changes in vascularity and blood flow are not well understood,
      candidate mediators include endothelin-1 (ET-1) and nitric oxide (NO). In the
      present study, we used a reverse transcriptase-polymerase chain reaction assay to
      determine which components of these vasoregulatory pathways are present in the
      thyroid and to analyze changes in gene expression in an experimental model of
      goiter formation and involution. Expression of messenger RNAs (mRNAs) encoding ET
      1, ET receptors (ETA and ETB), ET-converting enzyme, and the three nitric oxide
      synthase (NOS) isoforms (NOS I, NOS II, and NOS III) was readily detected in the
      rat thyroid. After goiter formation was induced by thiouracil and a low iodine
      diet, there was increased expression of the genes encoding ET-related proteins
      (ET-1, 3.2-fold; ETA, 2.9-fold; ETB, 3.5-fold) as well as two of the three NOS
      isoforms (NOS I, 2.7-fold; NOS III, 4.9-fold). During iodide-induced involution,
      the ET-related mRNA levels remained elevated, whereas those of the two NOS
      isoforms returned to basal values. ET-converting enzyme, NOS II, and
      thyroglobulin mRNAs were minimally affected in this model, providing evidence for
      selective regulation of these genes. To assess whether NO plays a role in
      vascular changes during goiter formation, animals were treated with a NOS
      inhibitor, N-nitro-L-arginine methyl ester (NAME). NOS activity in the thyroid
      was inhibited by more than 75% after treatment with NAME. Thyroid hormone and TSH
      levels were unchanged. Although NAME had little effect on overall thyroid size,
      vascular expansion during goiter formation was decreased by 36%. We conclude that
      the thyroid gland expresses a complex network of vasoactive genes whose
      expression is regulated dynamically during thyroid goiter formation and
      involution. NO production and probably other locally produced vasoactive
      substances are involved in changes in thyroid vascularization.

PMID- 7588274
TI  - A conformational change in the beta-subunit of the insulin-like growth factor I
      receptor identified by antipeptide antibodies.
AB  - Insulin-like growth factor I (IGF-I) binding to its receptor results in receptor
      autophosphorylation and phosphorylation of several cellular substrates. The
      mechanism by which binding of the ligand to the extracellular receptor domain
      activates the intracellular kinase remains to be defined. Using polyclonal
      antibodies against four regions of the IGF-I receptor, we searched for putative
      conformational changes occurring in purified receptors. We studied the ability of
      the antipeptide antibodies to immunoprecipitate the native, ligand-occupied, or
      autophosphorylated IGF-I receptor. We found that the antipeptide antibody
      directed to the sequence 985-998 of the kinase domain immunoprecipitated the
      phosphorylated receptor, but not the native or the ligand-occupied receptor. By
      contrast, the antibody against the sequence 950-957 of the juxtamembrane domain
      immunoprecipitated the three receptor forms. The difference between
      phosphorylated receptors and unphosphorylated receptors was not observed in
      Western blot experiments, indicating that the conformational modification of the
      receptors is not detected upon unfolding. These data demonstrate that the IGF-I
      receptor undergoes an autophosphorylation-induced conformational change
      detectable in the kinase domain. Our work provides evidence that conformational
      changes induced by autophosphorylation may be a common activation mechanism for
      tyrosine kinase receptors.

PMID- 7588275
TI  - Regulation by insulin-like growth factor (IGF) binding proteins of IGF-II
      stimulated glycogenesis in cultured fetal rat hepatocytes.
AB  - We previously showed that when added to fresh medium, insulin-like growth factor
      (IGF)-II stimulates glycogen synthesis in cultured 18-day-old fetal rat
      hepatocytes. In the present study, we investigated the influence of 24-h culture
      conditioned medium on IGF-II- and insulin-induced glycogenesis. The stimulatory
      effect of IGF-II (2.9-fold) on [14C]glucose incorporation into glycogen over 3 h
      was dose dependently inhibited by conditioned medium, whereas that of insulin
      (3.2-fold) was unaffected. Western ligand and immunoblot analysis of the
      conditioned media revealed IGF binding protein (IGFBP)-1, IGFBP-2, and IGFBP-4,
      with a predominance of IGFBP-1. IGFBP-3 was not detected. Preincubation of
      conditioned medium with IGF-II for 4 h at 4 C restored the glycogenic effect of
      newly added IGF-II. Preincubation of fresh medium with recombinant IGFBP-1 or
      IGFBP-3 in the presence of IGF-II suppressed IGF-II stimulation of glycogen
      synthesis. IGFBPs alone had no effect on glycogenesis. Des(1-6)IGF-II and R6IGF
      II, structural analogs of IGF-II that have weak affinity for the IGFBPs, elicited
      maximal stimulation, near that of IGF-II (2.8-fold and 3.1-fold vs. 3.0-fold for
      IGF-II), whether tested in fresh or conditioned medium. The inhibitory effect of
      conditioned medium on IGF-II-induced glycogenesis is therefore mediated by the
      IGFBPs via sequestration of IGF-II. This suggests that the IGFBPs, particularly
      IGFBP-1, produced by fetal rat hepatocytes in culture may play a role in
      regulating glycogenesis.

PMID- 7588277
TI  - Differential expression and regulation of connexin-43 and cell-cell coupling in
      myocytes from the circular and longitudinal layers of bovine myometrium.
AB  - The expression and localization of the gap junction protein connexin-43 (Cx-43)
      as well as functional coupling were studied in myocytes from the two layers of
      the bovine myometrium: the circular and the longitudinal layers. Intercellular
      communication (measured by Lucifer yellow dye transfer through gap junctions) was
      more intense in the circular than in the longitudinal layer of the bovine
      myometrium. The circular layer also exhibited a greater degree of punctuate
      immunofluorescence to Cx-43. Myocytes from the circular layer expressed more Cx
      43 messenger RNA (mRNA; 2.38 +/- 0.46, Cx-43 over 18S RNA) than the longitudinal
      layer (1.46 +/- 0.48, Cx-43 over 18S RNA; P < 0.05). The modulation of Cx-43
      expression by sex steroids in the two myometrial layers was tested using a pure
      steroidal antiestrogen, EM-139. In myocytes from the circular layer, the level of
      Cx-43 mRNA was decreased after treatment with 0.1 microM EM-139 (1.37 +/- 0.25,
      Cx-43 over 18S RNA) compared to that in untreated cells (2.38 +/- 0.46, Cx-43
      over 18S RNA), representing a 40% inhibition. In parallel, cell-cell coupling and
      the amount of Cx-43 protein were also reduced after antiestrogen treatment. In
      contrast, treatment of cells from the longitudinal layer with the antiestrogen
      did not significantly affect the level of Cx-43 mRNA, protein, or cell-cell
      coupling. These data demonstrate that Cx-43 protein and mRNA are expressed and
      regulated differentially in myocytes from the circular and longitudinal layers of
      bovine myometrium. Furthermore, the circular myometrial layer may represent a
      preferential target for estrogen regulation of the biochemical and mechanical
      processes controlling contractility.

PMID- 7588276
TI  - Induction of spermatogenesis by androgens in gonadotropin-deficient (hpg) mice.
AB  - Using a new experimental model for studying the hormonal induction of
      spermatogenesis, the hpg mouse, which has congenital functional gonadotropin
      deficiency due to a major deletion in the GnRH gene, we investigated the roles of
      testosterone (T) and dihydrotestosterone (DHT) in the initiation of
      spermatogenesis. Weanling homozygous hpg male mice were implanted subdermally
      with SILASTIC brand implants of varying lengths (0-2 cm) filled with T or DHT,
      using phenotypically normal (N/N or N/hpg) and untreated hpg/hpg mice as positive
      and negative controls. After 8 weeks, both T and DHT equally stimulated
      (approximately 14-fold) testis size and induced qualitatively complete
      spermatogenesis despite low intratesticular androgen levels and undetectable
      circulating FSH. Stereological quantitation of Sertoli and germ cells
      demonstrated a dose-dependent rise in the absolute numbers of all germ cell types
      induced by both T and DHT. At maximal androgen doses, germ cell numbers expressed
      per Sertoli cell and homogenization-resistant elongated spermatids expressed per
      mg testis were increased to more than 80% of non-hpg control values. An in vitro
      fertilization assay confirmed that both T and DHT induced quantitatively normal
      fertilizing capacity of the sperm in hpg males. We conclude that androgens,
      acting through the androgen receptor without need for aromatization, initiate
      qualitatively complete spermatogenesis in the mouse, including fertile sperm
      despite low intratesticular androgen levels and the absence of blood FSH levels.
      The hpg mouse model is a useful new paradigm to study the molecular basis of the
      hormonal induction of spermatogenesis.

PMID- 7588278
TI  - Gene expression of retinoic acid receptors, retinoid-X receptors, and cellular
      retinol-binding protein I in bone and its regulation by vitamin A.
AB  - We investigated the gene expression of retinoic acid (RA) receptors (RARs) and
      retinoid-binding proteins, and the effect of vitamin A on gene expression in the
      rat tibia to understand the actions of vitamin A on bone tissue. The transcripts
      of all three subtypes of all-trans RAR (alpha, beta, and gamma) and two of three
      subtypes of retinoid-X receptor (alpha and beta) were detected by Northern
      blotting. Among cellular retinol-binding protein I (CRBP-I) and CRBP-II and
      cellular retinoic acid-binding protein I and II, only the CRBP-I gene was
      expressed. These results indicated that in bone, the actions of vitamin A are
      exerted through these nuclear receptors by regulating target gene expression, and
      through CRBP-I by modulating the intracellular transport of vitamin A. Moreover,
      using rats of various retinoid status, we investigated whether the expression of
      target genes for vitamin A (RAR beta and CRBP-I) is regulated by retinoic acid
      (RA) in the adult rat tibia. The messenger RNA levels of these genes in vitamin A
      deficient rats decreased to half of those in normal rats and were quickly
      restored (4 h) by either all-trans-RA or 9-cis-RA. Excess RA given to normal rats
      doubled the messenger RNA levels of these two genes. These results verified that,
      like other target tissues, bone is a target for vitamin A in terms of gene
      expression. In addition, we examined the effect of RAs on the expression of the
      target genes for vitamin D, because it is possible that 9-cis-RA is involved in
      the transcriptional control of vitamin D receptor by forming a heterodimer
      complex with retinoid-X receptor. The vitamin D-regulated osteopontin gene was
      induced 4 h after the administration of RA regardless of retinoid or vitamin D
      status. RA also induced osteopontin gene expression in concert with vitamin D in
      normal rats. Specific inhibitors of transcription showed that gene expression may
      be regulated by RA at the transcriptional level. Thus, the results presented here
      clarified at the molecular level that bone is a target organ for vitamin A in
      terms of gene expression.

PMID- 7588279
TI  - A long-term increase in basal levels of corticosterone and a decrease in
      corticosteroid-binding globulin after acute stressor exposure.
AB  - Adrenal glucocorticoids play an important role in mediating many of the
      behavioral and physiological effects of exposure to stressors. Focus has been
      primarily on the acute stress-induced rise in glucocorticoids [corticosterone
      (CORT) in the rat]. There are reports, however, that exposure to chronic
      stressors can produce an increase in basal CORT and a decrease in corticotropin
      binding globulin (CBG). These changes occur subsequent to the stress-induced rise
      in CORT. The following experiments examined whether exposure to an acute stressor
      (100 5-sec inescapable tail shocks; IS) could also produce long term changes in
      basal CORT and CBG. We report that a single session of IS results in an increase
      in basal total serum CORT that persists 48-96 h after IS termination. The
      increase is present only at the diurnal trough (morning). CBG levels ae also
      decreased for 24-48 h. The decrease is present at both the diurnal peak (evening)
      as well as the trough (morning). These changes result in an increase in the
      percent and amount of biologically active CORT (unbound or free). Thus,
      glucocorticoid-sensitive targets are exposed to high levels of free CORT for
      several days after IS termination. The long term increase in free CORT reported
      here may play an important role in mediating some of the effects produced by IS
      as well as those produced by other acute stressors.

PMID- 7588280
TI  - Alpha 2-macroglobulin conformation determines binding affinity for activin A and
      plasma clearance of activin A/alpha 2-macroglobulin complex.
AB  - Activin A is a member of the transforming growth factor-beta family of growth
      factors and a potent regulator of cellular activity. A number of binding proteins
      for activin A have been identified, including alpha 2-macroglobulin (alpha 2M).
      Alpha 2M has several conformational states that are known to have different
      growth factor-binding properties. The effect of alpha 2M conformation on activin
      A binding has not been characterized. The aims of this study were to determine 1)
      whether activin A binds preferentially to the native (alpha 2M-N) or "activated"
      (alpha 2M*) conformation of alpha 2M, 2) the affinity of different alpha 2M
      conformations for activin A, and 3) the fate of activin A complexed with alpha 2M
      N or alpha 2M* in vivo. [125I]Activin A associated with alpha 2M in plasma and
      follicular fluid and with purified alpha 2Ms. In this qualitative assay, more
      activin A was associated with alpha 2M* than with alpha 2M-N. The affinity of the
      activin A-alpha 2M interaction was determined. The Kd values for activin A-alpha
      2M* and activin A-alpha 2M-N were 190 +/- 30 and 510 +/- 60 nM, respectively. The
      plasma clearance profiles and tissue distribution of uncomplexed activin A and
      purified alpha 2M*-activin A complex were determined. Radiolabeled activin A
      cleared in a biphasic manner, with rapid clearance over the initial 10 min and
      substantially slower clearance over the subsequent 20 min. During the slow phase
      of clearance, activin A formed a complex with circulating alpha 2M-N. In
      contrast, radiolabeled activin A-alpha 2M* complexes were rapidly cleared from
      plasma with a half-life of approximately 5 min and were specifically targeted to
      alpha 2M receptors in vivo. These studies reveal that alpha 2M can maintain
      activin A in the circulation or rapidly target the hormone for plasma clearance
      depending on the conformational state of the carrier protein in vivo.

PMID- 7588282
TI  - In vitro acute and prolonged effects of melatonin on purified rat Leydig cell
      steroidogenesis and adenosine 3',5'-monophosphate production.
AB  - The effects of melatonin (MLT; 4.3 pM to 4.3 microM) on rat Leydig cell
      steroidogenesis and cAMP production were investigated during 3-h LH (30 mIU/ml)
      stimulation. Having noted a dose-dependent inhibition of testosterone (T)
      release, we also tested MLT in the presence of the cAMP activator forskolin (1
      microM), the phosphodiesterase inhibitor isobutylmethylxanthine (100 microM), a
      combination of these two, and LHRH (100 nM), a non-cAMP-mediated stimulus.
      Regardless of the stimulus, levels of T, androstenedione, and cAMP were reduced,
      whereas that of 17-hydroxyprogesterone was enhanced. Cells were also tested after
      prolonged exposure to MLT (215 nM for 16 h). When compared with data from cells
      not preincubated with MLT, cAMP and T levels were 30% higher during LH
      stimulation (30 mIU/ml); comparable during treatment with forskolin (1 microM),
      isobutylmethylxanthine (100 microM), or their combination; and reduced during
      LHRH (100 nM). Scatchard analysis did not reveal changes in LH receptors during
      prolonged MLT exposure. Our data show that MLT acutely reduces cAMP- and non-cAMP
      stimulated T. This effect is linked in part to reduced cAMP production and in
      part to reduced 17-20-desmolase enzymatic activity, which, however, can occur
      even with non-cAMP-mediated stimulation. On the other hand, prolonged exposure to
      MLT results in sensitization of the LH-dependent adenylate cyclase activity.

PMID- 7588285
TI  - Molecular cloning and functional expression of a third isoform of the human
      calcitonin receptor and partial characterization of the calcitonin receptor gene.
AB  - We have cloned and expressed two isoforms of the human calcitonin (hCT) receptor.
      Primers designed from the published sequence of a CT receptor cloned from an
      ovarian small cell carcinoma line were used for the polymerase chain reaction
      amplification of related products from human breast carcinoma MCF-7 cells. Two
      complementary DNAs were isolated. One clone lacks a 16-amino acid insert in the
      first intracellular loop and is virtually identical to the receptor recently
      cloned from the T47D human breast carcinoma cell line. The second clone is
      another splice variant lacking both the 16-amino acid insert in the first
      intracellular domain as well as the first 47 amino acids of the amino-terminus
      extracellular domain. COS-7 cells transfected with either receptor isoform bound
      [125I]salmon CT with high affinity and responded to hCT with increases in cAMP.
      Tissue distribution studies revealed the truncated extracellular domain 1 isoform
      transcripts in human skeletal muscle, kidney, brain, and lung. Analysis of a hCT
      receptor genomic clone demonstrated an exon/intron organization similar to that
      of the porcine CT receptor gene, except for a distinct exon coding for the
      alternatively spliced insert in the first intracellular domain.

PMID- 7588286
TI  - Relationship between the thyroid hormone transport system and the Na(+)-H+
      exchanger in cultured rat brain astrocytes.
AB  - The entry of T3 and T4 into rat cultured astrocytes is mediated by a
      sterospecific saturable transport system. This study examines the effect of
      inhibiting the Na(+)-H+ exchanger and intracellular acidification on the initial
      velocity of [125I]T3 and [125I]T4 uptake. The resting intracellular pH (pHi) was
      approximately 7.15 in astrocytes exposed to CO2/HCO3(-)-free medium buffered with
      HEPES at pH 7.40 at 22 C. Isoosmotic replacement of extracellular sodium by
      mannitol or choline decreased the pHi by 0.15 pH unit and reduced uptake by about
      20%. Replacing sodium with lithium had no effect on uptake. Amiloride, a specific
      blocker of the Na(+)-H+ exchanger, reduced pHi, as described above, and inhibited
      T3 and T4 uptake by about 35%. Acid loading the cells with a NH4+ pulse decreased
      the pHi by up to 1.2 pH units and the uptake of T3 and T4 by up to 50%. The
      maximum velocity of uptake was decreased, whereas the Km was unchanged. An
      isoosmotic increase in the extracellular K+ concentration to 50 mM had no effect
      on T3 uptake. The initial velocity of T3 uptake by acid-loaded cells was
      gradually restored by increasing the extracellular Na+ concentration. These
      results indicate that thyroid hormone transport into rat cultured astrocytes
      involves a mechanism linked to the activity of the Na(+)-H+ exchanger and the H+
      concentration inside the cells.

PMID- 7588281
TI  - Oxytocin receptor gene expression in the rat uterus during pregnancy and the
      estrous cycle and in response to gonadal steroid treatment.
AB  - It is well established that uterine oxytocin receptors (OTRs) are strongly up
      regulated immediately before parturition as well as in response to estrogen (E2)
      administration. Progesterone (P4), on the other hand, induces a rapid down
      regulation. We recently cloned the rat OTR gene and characterized its expression
      in the rat uterus. In this study, we examined the regulation of OTR messenger RNA
      (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response
      to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during
      gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day
      21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85%
      within 24 h following parturition. By in situ hybridization, OTR mRNA was
      localized specifically to the longitudinal and circular layers of the myometrium
      but was not detected in the endometrium. During the estrous cycle, OTR mRNA
      levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT)
      binding rose more than 10-fold within this same interval. Treatment of
      ovariectomized rats with E2 lead to a significant increase in both OTR mRNA
      levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced
      OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise
      in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased
      expression of OT binding sites observed at the onset of labor and at proestrus is
      mediated, at least in part, by an E2-induced up-regulation of OTR gene
      expression. However, it also appears that OTR mRNA levels are not the sole
      determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation
      cannot be explained by an effect on OTR mRNA accumulation and may involve novel
      mechanisms acting at translational or posttranslational levels.

PMID- 7588284
TI  - In vivo effects of glucose and insulin on secretion and gene expression of
      glucagon in rats.
AB  - We investigated the effects of insulin and glucose on the control of secretion
      and gene expression of glucagon in vivo in rats. Animals were studied during 1) a
      48-h period of either glucose infusion (hyperglycemia plus hyperinsulinemia; HG
      HI rats) or insulin infusion (euglycemia plus hyperinsulinemia; EG-HI rats), and
      2) a prolonged postinfusion period in both groups. In HG-HI rats, elevation of
      plasma insulin and glucose concentrations by about 7 and 5 times, respectively,
      resulted in a decline in glucagon levels, which fell significantly within 6 h and
      remained low thereafter, whereas these levels were unchanged in EG-HI rats.
      Glucagon messenger RNA levels and pancreatic glucagon content were not
      significantly affected in either HG-HI or EG-HI rats. After cessation of
      infusions, hypoglycemia occurred in both group of rats. In HG-HI rats,
      hypoglycemia lasted for about 36 h without any surge in the plasma glucagon
      level, whereas in EG-HI rats it was transient (approximately 1 h) and stimulated
      glucagon secretion. In both groups the pancreatic alpha-cell was unresponsive to
      arginine during the postinfusion period. In conclusion, although a role of
      intraislet insulin cannot be excluded, glucagon gene expression is insensitive to
      changes in plasma glucose and insulin concentrations. In contrast,
      hyperglycemia/hyperinsulinemia, not hyperinsulinemia alone, lowers glucagon
      secretion and affects the alpha-cell responsiveness to hypoglycemia.

PMID- 7588283
TI  - The effects of nitric oxide on the membrane potential and ionic currents of mouse
      pancreatic B cells.
AB  - Nitric oxide (NO) is considered to contribute to the impairment of B cell
      function in insulin-dependent diabetes mellitus. The effects of compounds that
      release NO were tested on the membrane potential and ionic currents of mouse
      pancreatic B cells using intracellular microelectrodes and the whole-cell patch
      clamp technique. S-Nitrosocysteine led to a concentration-dependent reduction of
      electrical activity induced by 15 mM glucose. At a concentration of 1 mM, S
      nitrosocysteine cause a hyperpolarization of the plasma membrane with complete
      suppression of electrical activity. In about half of the cells tested, electrical
      activity reappeared during treatment with S-nitroso-cysteine or after wash-out.
      However, in the other cells the hyperpolarization was followed by a slow
      depolarization and electrical activity did not reappear. The perforated-patch
      whole-cell K+ATP current first increased and subsequently decreased again during
      exposure to 1 mM S-nitroso-cysteine. With 0.1 and 0.01 mM S-nitroso-cysteine,
      only the rise of the current amplitude was observed. S-nitroso-cysteine (1 mM)
      almost completely abolished the current through voltage-dependent Ca2+ channels
      (measured with Ba2+ as charge carrier). Like S-nitroso-cysteine, 100 microM
      sodium-nitroprusside, another donor, evoked a marked hyperpolarization of the
      membrane potential that was at least in part reversible. To further ascertain
      that the effect of S-nitroso-cysteine was mediated by NO, we tested the
      decomposition products of S-nitroso-cysteine. Nitrite and denitrosylated S
      nitroso-cystein (1 mM) did not alter electrical activity of B cells, whereas
      cysteine (1 mM) caused a slight depolarization. It is concluded that exogenous NO
      evokes rapid changes of B cell function by influencing the activity of ion
      channels.

PMID- 7588288
TI  - Role of inositol trisphosphate-sensitive calcium stores in the regulation of
      adrenocorticotropin secretion by perifused rat anterior pituitary cells.
AB  - Intracellular Ca2+ (Cai2+) stores contribute significantly to Ca2+ signaling in
      many types of cells. We studied the role of inositol trisphosphate (InsP3)
      sensitive Ca2+ stores, a principal Cai2+ store that presumably is within the
      endoplasmic reticulum (ER), in cell signaling by examining the effect of
      thapsigargin (Tg), an ER Ca2+ pump inhibitor that depletes the ER Ca2+ pool, on
      ACTH secretion. Preincubation for 6-24 h with 2-20 nM Tg had no effect on the
      resting cytosolic free Ca2+ concentrations ([Cai2+]) but inhibited the ionomycin
      stimulated spike-type increase in [Cai2+], which is mediated by InsP3-independent
      Cai2+ release from the ER, in a dose-dependent (IC50, 4 nM) and time-dependent
      manner. In ER Cai(2+)-depleted cells, the spike phase (initial 5 min) of the ACTH
      secretory response to arginine vasopressin (AVP), which is mediated by InsP3
      induced Cai2+ release, was also attenuated (IC50, 7.3 nM). However, the spike
      phase of the ACTH secretory response to AVP was inhibited to a much greater
      degree than the spike-type response to ionomycin, suggesting that ER Cai2+ stores
      might have functions other than simply providing Ca2+ for InsP3-stimulated Cai2+
      release. Tg pretreatment (IC50, 12 nM) also markedly inhibited the sustained
      plateau (final 15-min) phase of the ACTH secretory response to AVP, which is
      mediated by diacylglycerol-induced activation of protein kinase C and subsequent
      influx of extracellular Ca2+ via L-type voltage-sensitive Ca2+ channels (VSCC),
      but had no effect on the sustained (full 20 min) response to dioctanoylglycerol
      that directly activates protein kinase C. Tg had no effect on specific cell
      binding of [125I]AVP or on specific cell binding of [3H]phorbol 12,13-dibutyrate
      (except at 20 nM Tg), an index of protein kinase C concentration, or on protein
      kinase C activity. AVP significantly stimulated inositol trisphosphate
      accumulation, but pretreatment with Tg completely abolished this effect of AVP,
      whereas [3H]myoinositol incorporation into membrane-associated inositol lipids
      and inositol phosphates was unaffected. Thus, Tg-induced depletion of ER Cai2+
      stores inhibited both the spike and plateau phases of the ACTH secretory response
      to AVP, presumably by inhibiting phospholipase C activity and the resulting
      generation of InsP3 and diacylglycerol. Preincubation with Tg inhibited, in a
      dose-dependent (IC50, 13 nM) and time-dependent manner, the sustained ACTH
      secretory response to corticotropin-releasing hormone (CRH) that is mediated by
      cAMP-induced activation of protein kinase A and Cae2+ influx via L-type VSCC, and
      the sustained response to forskolin, which directly activates adenylate
      cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588287
TI  - Retinoic acid induces expression of the transcription factor GHF-1/Pit-1 in
      pituitary prolactin- and growth hormone-producing cell lines.
AB  - PRL and GH gene expression depend on the presence of the pituitary-specific
      transcription factor GHF-1/Pit-1. We have examined the effects of retinoic acid
      (RA) on the expression of the GHF-1/Pit-1 gene. RA induced a time- and dose
      dependent increase in GHF-1/Pit-1 messenger RNA in the PRL-producing cell line
      235-1. A maximal effect (a 2- to 3-fold increase) was obtained after 12-24 h of
      incubation with 1 microM RA. The level of the transcription factor determined by
      both Western blotting and gel retardation analysis with a GHF-1/Pit-1-binding
      site was increased in RA-treated cells compared to that in control cells.
      Sequences located between -400 and -90 bp mediated a 2- to 3-fold activation of
      the GHF-1/Pit-1 promoter by RA. The retinoid also increased the response to cAMP
      and phorbol esters that is mediated by two cAMP-responsive elements (CREs)
      located in the same promoter fragment. Both CREs are required for RA induction,
      as deletion of either CRE abolished the response to the retinoid RA also induced
      GHF-1/Pit-1 gene expression in GH4C1 cells, which produce both PRL and GH. T3 did
      not affect expression of the GHF-1/Pit-1 gene in 235-1 cells, but decreased basal
      GHF-1/Pit-1 messenger RNA and promoter activity in GH4C1 cells and blocked the
      stimulatory effect of RA.

PMID- 7588290
TI  - Regulation in vivo of the growth of Leydig cell tumors by antisense ribonucleic
      acid for parathyroid hormone-related peptide.
AB  - PTH-related peptide (PTHrP) has been shown to be the major mediator of
      hypercalcemia of malignancy, but may also exert effects on cell growth and
      differentiation. The Leydig cell tumor H-500, when implanted in Fischer rats,
      produces abundant PTHrP and eventually causes the death of the host animal. In
      the present study we have used antisense RNA technology to block the effects of
      PTHrP in H-500 Leydig tumor cells in vivo. The full-length rat PTHrP
      complementary DNA encoding amino acid -36-->141 was subcloned as an EcoRI-BglII
      insert in the antisense orientation into the mammalian expression vector pRc/CMV
      to produce the plasmid pRc-PAS. This plasmid was then stably transfected into the
      H-500 Leydig tumor cells with a Lipofectin reagent. After selection with the
      neomycin derivative G-418, a stable cell line, H-500-PTHrP-AS, was obtained which
      showed 80% inhibition of endogenous PTHrP messenger RNA compared to wild-type or
      vector-only transfected H-500 cells. Conditioned culture medium from these
      experimental cells showed a marked decrease in PTHrP immunoreactivity and in the
      ability of the medium to stimulate adenylate cyclase in UMR-106 rat osteosarcoma
      cells. Furthermore, inhibition of PTHrP production resulted in a significant
      increase in the doubling time of the H-500 cells. Transfection of the
      experimental plasmid into Rat-2 fibroblasts, which do not produce PTHrP, had no
      effect on cell growth. Control and experimental cells were then implanted sc into
      male Fischer rats. Animals were killed at timed intervals, and their tumor
      volumes were determined. Experimental animals receiving cells transfected with
      antisense PTHrP plasmid showed near-normal levels of plasma calcium and decreased
      expression of tumoral PTHrP messenger RNA. These animals also showed a 30-70%
      lower tumor volume during the course of the experiment compared to control
      animals. These studies have demonstrated that PTHrP can play a role as a promoter
      of tumor growth in vitro and in vivo.

PMID- 7588289
TI  - Steady state steroid 5 alpha-reductase messenger ribonucleic acid levels and
      immunocytochemical localization of the type 1 protein in the rat testis during
      postnatal development.
AB  - Steroid 5 alpha-reductase is the rate-limiting enzyme in the production of 5
      alpha-reduced steroids in many tissues. Developmental changes in 5 alpha
      reductase activity play an important role in regulating the amount of
      testosterone that is secreted by the testis. To date, the regulation of
      testicular 5 alpha-reductase has been studied extensively at the level of enzyme
      activity. Regulation at the messenger RNA (mRNA) and protein levels, however, has
      not been investigated. The objectives of the present study were to determine the
      steady state mRNA levels for the 5 alpha-reductase isozymes, types 1 and 2, and
      to immunolocalize the 5 alpha-reductase type 1 protein in the developing rat
      testis (7-91 days postpartum). Consistent with previously reported enzyme
      activity studies, type 1 5 alpha-reductase mRNA levels were most abundant in the
      immature animal (days 21-28). Unlike 5 alpha-reductase activity, however, type 1
      mRNA levels did not decline thereafter to reach nearly undetectable levels in the
      adult (day 91). In contrast, 5 alpha-reductase type 1 mRNA levels remained
      relatively constant between days 42-91. The 5 alpha-reductase type 1 transcript
      size did not remain constant during postnatal testicular development. The
      characteristic 2.5-kilobase type 1 transcript size was detected in immature rats
      (days 21-28), whereas in the adult (day 91), a slower migrating 2.7-kilobase type
      1 mRNA species was observed. An antipeptide antiserum specific to rat 5 alpha
      reductase type 1 was used to immunolocalize the 5 alpha-reductase type 1 protein.
      At all ages examined, the immunoperoxidase reaction was localized predominantly
      to the interstitial tissue of the testis. On postnatal day 7, clusters of
      interstitial cells resembling fetal Leydig cells were clearly immunoreactive. The
      staining intensity increased steadily from day 7 onwards, so that by days 21 and
      28, interstitial cells with the appearance of immature Leydig cells were
      intensely immunoreactive (peak expression). This was followed by a progressive
      decrease in staining intensity between days 28-91, so that by day 91 (adult)
      Leydig cell immunoreactivity was barely detectable. Immunocytochemical staining
      revealed a predominantly cytoplasmic localization; significant nuclear staining
      was not evident. We conclude that the expression of the 5 alpha-reductase type 1
      protein is primarily found in the cytoplasm of Leydig cells, is dependent on age,
      and that this expression closely parallels 5 alpha-reductase enzyme activity.

PMID- 7588291
TI  - Hormonal regulation of messenger ribonucleic acid encoding steroidogenic acute
      regulatory protein in ovine corpora lutea.
AB  - Steroidogenic acute regulatory protein (StAR), proposed to be involved in the
      transport of cholesterol to the inner mitochondrial membrane, has recently been
      cloned from MA-10 cells. Using reverse transcription-polymerase chain reaction,
      we generated a complementary DNA encoding 404 base pairs of StAR from ovine
      luteal tissue to perform studies regarding regulation of the messenger RNA (mRNA)
      encoding this protein. In Exp 1, ewes were hypophysectomized (HPX) on day 5 of
      the estrous cycle and administered saline or physiological regimens of LH and/or
      GH until collection of luteal tissue on day 12 of the estrous cycle (n =
      4/group). Luteal concentrations [mean +/- SEM; femtomoles per microgram poly(A)+
      RNA] of mRNA encoding StAR were lower (P < 0.05) in the HPX plus saline-treated
      ewes (26.4 +/- 7.3) than in day 12 pituitary-intact ewes (n = 4; 77.7 +/- 9.3).
      Replacement of LH (59.1 +/- 13.1), GH (59.1 +/- 12.8), or LH and GH (69.9 +/-
      4.5) in HPX ewes increased (P < 0.05) concentrations of mRNA encoding StAR to
      values not different from those in day 12 controls. In Exp 2, ewes on day 11 or
      12 of the estrous cycle were injected with prostaglandin F2 alpha (PGF2 alpha) to
      induce luteal regression. Corpora lutea were collected 4, 12, or 24 h after
      injection (n = 4-5/time point) and from untreated control ewes (n = 4) or 24 h
      after injection of saline (n = 4). Treatment with PGF2 alpha decreased (P < 0.05)
      concentrations of progesterone in serum 4, 12, and 24 h after injection.
      Concentrations of StAR mRNA were decreased (P < 0.01) to 47%, 19%, and 8% of
      control values 4, 12, and 24 h after PGF2 alpha injection, respectively. In Exp
      3, ewes received ovarian arterial infusions of saline, PGF2 alpha, or phorbol 12
      myristate 13-acetate (PMA), and luteal tissue was collected 0 (no infusion), 4,
      12, or 24 h later (n = 3-4/group). Treatment with PGF2 alpha or PMA decreased (P
      < 0.05) concentrations of progesterone in serum 4, 12, and 24 h postinjection.
      Steady state concentrations of mRNA encoding StAR (P < 0.05) were 36% and 25% of
      the control value 12 and 24 h after PGF2 alpha injection. Injection of PMA
      decreased (P < 0.05) concentrations of StAR mRNA to 75% and 50% of control values
      at 4 and 12 h, but concentrations of mRNA encoding StAR were not different from
      control values at 24 h.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588292
TI  - Cis-regulatory elements conferring cyclic 3',5'-adenosine monophosphate
      responsiveness of the progesterone receptor gene in transfected rat granulosa
      cells.
AB  - We have previously shown that both pituitary gonadotropins and forskolin induce
      progesterone receptor (PR) messenger RNA expression at the level of transcription
      in granulosa cells of the rat ovary. To determine the DNA regulatory elements
      that are important for cAMP-induced transcription of the PR gene in the ovary, we
      examined the cAMP-induced activity of promoter sequences in rat granulosa cells
      transfected with various fusion constructs containing PRB promoter sequences
      linked to the luciferase reporter gene. When cells were transfected with a
      luciferase fusion construct containing the 1375-base pair 5'-flanking region of
      the rat PRB gene, forskolin treatment substantially increased luciferase
      activity. Analysis of a series of 5'-deletion mutants indicated that a minimal
      PRB promoter containing 116 base pairs of upstream sequence (-116/3) was
      sufficient to increase luciferase activity in response to forskolin in
      transfected rat granulosa cells. This promoter contains a consensus CCAAT site in
      reverse orientation (5'-ATTGG-3') and a consensus GC box (5'-GGGGCGGGCC-3'), but
      no known cAMP-responsive element. Site-specific mutation of the GC box notably
      decreased both basal and cAMP-induced activity of this minimal PRB promoter. In
      addition, site-specific mutation of the CCAAT binding site within this proximal
      promoter of the PRB gene substantially decreased cAMP-induced activity, but did
      not significantly affect the basal activity of this promoter. Either mutation
      alone failed to abolish cAMP inducibility. In contrast, double mutation of both
      the GC box and the CCAAT box completely abolished cAMP inducibility, suggesting
      that the GC box and the CCAAT box act together to mediate cAMP-induced
      transcription of the PRB gene. Gel shift analysis shows that the minimal PRB
      promoter sequences form multiple complexes with nuclear proteins of granulosa
      cells, all of which are specifically competed by oligonucleotides containing the
      GC box and the CCAAT box. Taken together, our results suggest a functional role
      for transcription factors binding the GC box and the CCAAT box in mediating cAMP
      induced transcription of the rat PRB promoter in rat granulosa cells.

PMID- 7588293
TI  - Activin stimulates Sertoli cell proliferation in a defined period of rat testis
      development.
AB  - The action of activin-A on Sertoli and spermatogonial cell proliferation during
      early postnatal life was studied by using in vitro organ culture of testis
      fragments from 9-day-old rats. Activin significantly stimulated 3H-thymidine
      incorporation into testis fragments cultured for 3 days in the presence of FSH,
      whereas it had no effect in the absence of the hormone. This effect was dose
      dependent in the range 10-200 ng/ml and was specifically inhibited by the activin
      binding protein, follistatin. The effect of activin upon proliferation of
      different testicular cells was studied in detail by 5-bromo-2'-deoxyuridine
      labeling fragments at the end of in vitro culture and then determining
      percentages of different labeled cells on immunostained histological sections.
      Concomitant treatment with FSH and activin, but not with FSH or activin alone,
      significantly stimulated Sertoli cell proliferation but markedly depressed that
      of differentiating type A spermatogonia. In contrast, proliferative activity of
      undifferentiated type A spermatogonia was independent of activin, irrespective of
      the presence of FSH. The effect of donor animal age was then investigated by
      culturing fragments derived from 3- and 18-day-old rats for 3 days. An age
      related response was evident. Sertoli cell proliferation was stimulated by FSH
      alone in fragments from 3-day-old rats, activin having no apparent effect at this
      age. In contrast, none of the hormones tested either alone or in combination was
      effective in 18-day-old animals. These results demonstrate that activin acts with
      FSH in maintaining mitotic potentiality of Sertoli cells in a defined phase of
      their maturation path, when their proliferative activity is approaching the final
      arrest. These findings suggest that activin may be an important local factor in
      regulating Sertoli cell number and that the mitosis of differentiating
      spermatogonia subsides during Sertoli cell proliferation.

PMID- 7588294
TI  - Cytokine-stimulated expression of inducible nitric oxide synthase by mouse, rat,
      and human osteoblast-like cells and its functional role in osteoblast metabolic
      activity.
AB  - Recent evidence suggests that the production of nitric oxide (NO) may have
      important roles in the regulation of osteoblast and osteoclast metabolism. The
      present study was performed to investigate the effects of interleukin-1 beta (IL
      1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN
      gamma) on the expression of inducible NO-synthase (iNOS) and to measure high
      output production of NO by primary rat osteoblasts and osteoblastic cell lines
      ROS 17/2.8, MC3T3-E1 and MG-63. In addition, we have investigated if NO may
      mediate some of the effects of these cytokines on osteoblast metabolism. Northern
      blots and immunocytochemistry revealed time-dependent iNOS messenger RNA and
      protein expression in primary rat osteoblasts in response to cytokine treatment.
      Reverse transcription polymerase chain reaction amplified an 807-base pair (bp)
      product from ROS 17/2.8 cells, which had a size and restriction enzyme-cut
      pattern identical to that predicted for authentic rat iNOS. Nitrite accumulation
      in culture medium was induced by IFN-gamma in a time- and dose-dependent manner
      and inhibited by cotreatment with inhibitors of NOS activity and by
      dexamethasone. IL-1 beta, TNF-alpha, and bacterial lipopolysaccharide were found
      to have weak stimulatory effects on nitrite production on their own. However, IL
      1 beta and TNF-alpha showed strong synergy with IFN-gamma, but, surprisingly,
      lipopolysaccharide was found to exert potent inhibitory effects on IFN-gamma
      induced nitrite synthesis. Basal production of nitrite and induction of its
      synthesis was similarly observed with primary rat osteoblasts as well as ROS
      17/2.8, MC3T3-E1, and MG-63 cell lines. Cytokine-induced NO production
      significantly reduced osteoblast activity, as was evidenced by inhibition of DNA
      synthesis, cell proliferation, alkaline phosphatase activity, and osteocalcin
      production. The results provide evidence for a basal expression of iNOS activity
      and show that the iNOS messenger RNA, protein, and enzyme activity are all
      induced by cytokines across the species. The data further suggest that osteoblast
      derived NO may have an important role in mediation of localized bone destruction
      associated with inflammatory bone diseases such as rheumatoid arthritis.

PMID- 7588295
TI  - A 14-kilodalton prolactin-like fragment is secreted by the hypothalamo
      neurohypophyseal system of the rat.
AB  - The recently described expression of the PRL gene, and the occurrence of a 14
      kilodalton (kDa)PRL-like immunoreactive protein in the hypothalamo
      neurohypophyseal system of the rat have raised the possibility that PRL variants
      are released from neurohypophyseal terminals into the blood. In this study, we
      investigated the local production of a hypothalamo-neurohypophyseal 14-kDa PRL
      like protein by showing an independent origin from adenohypophyseal PRL. No 14
      kDa PRL-like protein was detected in adenohypophyseal extracts by Western blots,
      whereas chronic hypophysectomy produced no change in the immunocytochemical
      detection of PRLs in supraoptic and paraventricular magnocellular neurons. In
      addition, a 14-kDa immunoreactive PRL-like protein was released into the medium
      by incubated neurohypophyseal lobes. Western blot analysis showed that
      significantly more of this 14-kDa protein was released into calcium-containing
      medium (1.8 mM) than into calcium-free medium. Furthermore, depolarizing
      concentrations of potassium (56 mM) increased by 3-fold the release of
      immunoreactive PRL by incubated hypothalamo-neurohypophyseal explants. In
      addition, a 14-kDa PRL-like antigen was detected in the circulation of the rat by
      Western blot analysis. These results are consistent with the local synthesis and
      calcium-dependent release of neurohypophyseal PRL-like proteins that include a
      predominant 14-kDa form.

PMID- 7588297
TI  - Platelet-derived growth factor stimulates the synthesis of interleukin-6 in cells
      of the osteoblast lineage.
AB  - Platelet-derived growth factor (PDGF) increases bone resorption and the number of
      osteoclasts in calvarial sections, and it may regulate local cytokines involved
      in bone remodeling. Interleukin-6 (IL-6), a cytokine secreted by osteoblasts,
      osteoclasts, and stromal cells, is known to increase osteoclast recruitment. We
      tested the effects of PDGF on IL-6 expression in cultures of osteoblast-enriched
      cells from 22-day-old fetal rat calvariae (Ob cells). Treatment of Ob cells with
      PDGF BB caused a time- and dose-dependent induction of IL-6 messenger RNA (mRNA),
      as determined by Northern blot analysis. The effect was maximal after 1 h of
      treatment and was observed with PDGF BB at 0.3-3.3 nM. Treatment with PDGF BB for
      24 h also increased IL-6 polypeptide levels in the culture medium, as determined
      by a specific bioassay. Although PDGF AA increased IL-6 mRNA levels, its effect
      was less pronounced than that of PDGF BB. Phorbol 12-myristate 13-acetate (PMA)
      induced IL-6 transcripts, and the effect of PDGF BB was inhibited in the presence
      of the protein kinase C (PKC) inhibitor, sangivamycin, or after down-regulation
      of PKC by PMA preincubation. Although forskolin increased IL-6 mRNA levels, PDGF
      BB did not induce cAMP production in Ob cells. The calcium ionophore, ionomycin,
      enhanced IL-6 transcripts in Ob cells and the intracellular calcium chelator, 1,2
      bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)
      ester, inhibited the induction of IL-6 transcripts by PDGF BB, PMA, and PTH. In
      conclusion, PDGF BB stimulates IL-6 expression in Ob cells, a response that is
      PKC and calcium dependent. The increase in IL-6 expression may be relevant to the
      actions of PDGF BB on bone resorption.

PMID- 7588296
TI  - Apoptosis contributes to the involution of beta cell mass in the post partum rat
      pancreas.
AB  - A significant reduction of beta cell mass has been described during the post
      partum period in the endocrine rat pancreas. We examined the mechanisms of this
      involution in Sprague Dawley rats by analyzing beta cell mass, beta cell
      replication, and beta cell size at end of pregnancy and 4 and 10 days after
      delivery. beta cell replication was significantly decreased at 4 days post partum
      but had returned back to nonpregnant levels by 10 days post partum. Similarly,
      beta cell size was significantly decreased at 4 and 10 days post partum as
      compared with the end of pregnancy, and at 10 days post partum was significantly
      decreased as compared with controls. At 4-6 days post partum, DNA fragmentation
      characteristic of apoptosis (programmed cell death) was detected in pancreatic
      islets, as assessed by in situ terminal deoxynucleotidyl transferase and nick
      translation assay. Only occasional cells were labeled with this assay in
      nonpregnant rats and at other time points after delivery. Condensed chromatin and
      apoptotic bodies, the morphological characteristics of apoptosis, were detected
      in beta cells of pancreatic islet at 3 and 4 days after delivery by electron
      microscopic analysis, confirming the occurrence of apoptosis in involuting
      islets. The expression of TRPM 2 and TGF beta 1, often enhanced in models of
      apoptosis, were studied during the post partum period by Northern blot analysis
      and immunohistochemistry. Levels of TRPM 2 gene and its protein, clusterin, were
      not different from controls; however, the TGF beta 1 gene and its protein
      expression were enhanced at 3 days post partum. Our study confirms the capability
      of beta cells to down-regulate their mass using the mechanisms of changes in
      rates of beta cell replication and of beta cell death, and changes in beta cell
      size to achieve homeostasis of the functional endocrine tissue.

PMID- 7588298
TI  - Regulation of the src homology 2 domain-containing protein tyrosine phosphatase
      PTP1C by glucocorticoids in rat pancreatic AR42J cells.
AB  - The effect of glucocorticoids, known to induce inhibition of growth and
      differentiation of pancreatic cells, has been examined on the tyrosine
      phosphatase containing two src homology 2 domains, PTP1C, in rat pancreatic
      cancer AR42J cells. Immunoblotting analysis revealed that PTP1C protein was
      present in AR42J cells as two PTP1C species of 66 and 31 kilodaltons (kDa), the
      31-kDa species representing a proteolytic product of the larger form.
      Dexamethasone increased the level of the two PTP1C species by 2 to 3 times.
      Nearly 80% of the PTP1C molecules were found in the particulate fraction in
      control cells and dexamethasone did not change the distribution of PTP1C. The
      increase of PTP1C protein was also detected by immunohistochemical analysis.
      Dexamethasone increased the tyrosine phosphatase activity of immunoprecipitated
      PTP1C. In addition, dexamethasone raised the level of expression of PTP1C
      messenger RNA in a time- and dose-dependent manner in relation with its effect on
      cell growth and differentiation. This effect was selective, the messenger RNA
      levels of the other tyrosine phosphatase containing two src homology 2 domains
      (SH2), PTP1D, and that of the cytosolic PTP1 being not affected. This is the
      first report of glucocorticoid increase of PTP1C expression, suggesting that
      PTP1C may be involved in the glucocorticoid-mediated pancreatic cell
      differentiation.

PMID- 7588299
TI  - Autocrine regulation of cell proliferation by the insulin-like growth factor
      (IGF) and IGF binding protein-3 protease system in a human prostate carcinoma
      cell line (PC-3).
AB  - PC-3 cells, whose growth is androgen-independent, were shown to be capable of
      slow proliferation in serum-free medium and in the absence of added growth factor
      for 7 days. They secreted insulin-like growth factor (IGF)-II but no detectable
      IGF-I. This IGF-II, although produced in small amounts, plays a role in their
      proliferation because growth could be inhibited dose dependently by up to 80% in
      the presence of monoclonal antibodies directed against IGFs or the type 1 IGF
      receptor. PC-3 cells also secreted IGF binding proteins (IGFBPs) -2, -3, -4, and 
      6. Immunoblot analysis revealed selective proteolysis of IGFBP-3, yielding
      fragments of the same molecular size as those generated from IGFBP-3 in vivo.
      With the addition to the culture medium of a serine protease inhibitor, 4-(2
      aminoethyl)-benzenesulfonyl fluoride (Pefabloc-SC), at concentrations < 0.2 mM
      that were nontoxic to the cells, cell proliferation was dose dependently
      inhibited up to 80% and, at the same time, proteolysis of the IGFBP-3 secreted by
      the cells was depressed. Urokinase activity detected in the conditioned media was
      depressed by Pefabloc, suggesting that the urokinase-type plasminogen activator
      was involved in the proteolysis of IGFBP-3. In addition, 0.01-5 micrograms/ml
      plasminogen induced a dose-dependent increase in both proliferation and the
      proportions of proteolysed IGFBP-3 in the media. The stimulation of proliferation
      was totally blocked in the presence of anti-type 1 IGF receptor antibody.
      Recombinant human IGF-II (5-200 ng/ml) added to cell-free medium conditioned by
      48 h of culture dose dependently stimulated PC-3 cell proliferation. At
      concentrations < or = 100 ng/ml, its mitogenic action was potentiated when medium
      had been conditioned by cells cultured in the presence of plasminogen but
      inhibited when medium had been conditioned by cells cultured in the presence of
      Pefabloc. We conclude from these results 1) that IGF-II is involved in the
      autocrine control of PC-3 cell proliferation via the type 1 IGF receptor; and 2)
      that this proliferation is directly dependent on IGF-II bioavailability that
      itself is modulated by the limited IGFBP-3 proteolysis induced, at least in part,
      by urokinase-type plasminogen activator and plasmin.

PMID- 7588301
TI  - Corticotropin-releasing hormone differentially modulates the interleukin-1 system
      according to the level of monocyte activation by endotoxin.
AB  - The interleukin-1 (IL-1) system is constituted by IL-1 alpha and IL-1 beta and IL
      1 receptor antagonist (IL-1ra) that bind the same IL-1 receptors. Hypothalamic
      pituitary-adrenal axis hormones are major mediators of the neuroendocrine control
      over immune function. Corticotropin-releasing hormone (CRH) is produced in
      peripheral inflammatory sites; its direct effects on inflammatory cytokine
      synthesis, however, remain unclear. We have studied the effects of CRH (0.1-100
      nM) on IL-1 beta and IL-1ra expression by human peripheral monocytes in culture
      activated with different doses of lipopolysaccharide (LPS). In the absence of
      LPS, CRH up-regulated IL-1ra and IL-1 beta messenger RNA expression as well as
      protein synthesis. No significant changes were observed with low doses of LPS (1
      ng/ml). In contrast, in combination with high doses of LPS (1 microgram/ml), CRH
      caused inhibition of IL-1ra and IL-1 beta transcription and secretion. The CRH
      effects were blocked by its antagonist alpha-helical CRH and mediated by
      intracellular cAMP. These data indicate that CRH modulates the IL-1 system;
      depending on the state of activation of the monocyte, CRH exerts an inhibitory
      control on the activated cell and a stimulatory action on the resting monocyte.

PMID- 7588300
TI  - Inactivation of activin-dependent transcription by kinase-deficient activin
      receptors.
AB  - Activin, a member of the transforming growth factor-beta superfamily, binds to
      two classes of cell surface receptors. These receptors, designated type I and
      type II, are structurally related members of transmembrane serine kinase
      superfamily. Antibodies specific for either type I or type II activin receptor
      can coprecipitate complexes containing both affinity-labeled receptors from
      activin-responsive cells. Two type I receptors show cell-specific expression and
      associate with the ligand-binding, type II receptors. To investigate the roles of
      the cytoplasmic receptor domains in signaling through a heteromeric ligand
      receptor complex, we have made kinase-deficient activin receptors and correlated
      their losses in kinase activity with inhibitory effects on an activin-dependent
      transcriptional response in activin-responsive cell lines. Wild-type activin type
      II receptors phosphorylate activin type I receptors in transfected COS cells. In
      contrast, kinase-deficient activin type II receptors fail to phosphorylate type I
      receptors in transfected COS cells and act as dominant negative mutants to block
      activin-induced transcriptional activity in both Chinese hamster ovary and K562
      (human erythroleukemia) cells. Kinase-deficient activin type IB receptors also
      block activin-induced transcriptional activity in both Chinese hamster ovary and
      K562 cells, whereas kinase-deficient activin type I receptors have no effect in
      either cell line. These results indicate that kinase activities of both type II
      and type I receptors are required for activin signaling, and that the two type I
      receptors, which are expressed in a tissue-specific manner, are functionally
      distinct.

PMID- 7588302
TI  - Does estradiol induce the preovulatory gonadotropin-releasing hormone (GnRH)
      surge in the ewe by inducing a progressive change in the mode of operation of the
      GnRH neurosecretory system.
AB  - Estradiol profoundly influences GnRH secretion during the follicular phase of the
      estrous cycle of the sheep. Estradiol not only regulates the frequency and
      amplitude of GnRH pulses, but also produces qualitative changes in its pattern of
      release and induces a sustained GnRH surge during which discrete pulses are not
      readily evident. In this study, we tested the hypothesis that qualitative changes
      in GnRH secretion are an integral part of an estradiol-induced change in the mode
      of operation of the GnRH neurosecretory system that leads to generation of the
      GnRH surge. This was achieved by the measurement of GnRH in samples of pituitary
      portal blood collected at 1-min intervals for an 11-h period encompassing the pre
      and early surge periods in an artificial follicular phase model. In each of the
      seven ewes studied, a highly characteristic alteration in the moment to moment
      pattern of GnRH was observed. This consisted of a progressive change from a
      strictly episodic pattern of GnRH release to one containing both episodic and
      nonepisodic components and, after amplification of both components, a period of
      extremely high values during which individual episodic increases were no longer
      readily recognizable. Preliminary mathematical modeling of the data suggested
      that these patterns could be produced by a change in GnRH from a predominantly
      low to a mixture of low and high amplitude inputs. Similar changes in minute to
      minute patterns of GnRH secretion were observed during the natural follicular
      phase. These findings are consistent with the hypothesis that estradiol induces
      the GnRH surge by altering the mode of neurosecretion, rather than by merely
      causing quantitative changes in the episodic pattern of release.

PMID- 7588303
TI  - Tissue-specific regulation by vitamin D status of nuclear and mitochondrial gene
      expression in kidney and intestine.
AB  - Vitamin D is responsible, through the actions of its metabolite, 1 alpha,25
      dihydroxyvitamin D3 [1 alpha,25-(OH)2D3], for the generation of a wide array of
      biological responses, particularly in the intestine, kidney, and bone. 1 alpha,25
      (OH)2D3 is known to interact with its nuclear receptor to mediate the regulation
      of gene transcription. Although many genes and gene products have been shown to
      be regulated by 1 alpha,25-(OH)2D3 (e.g. calbindin-D28K in the intestine and
      kidney; collagen, osteocalcin,and osteopontin in bone), their recognition has
      been largely the result of empirical testing. In this report we have used
      subtractive hybridization analysis of complementary DNA libraries prepared from
      messenger RNA (mRNA) isolated from the intestine and kidney of vitamin D-replete
      or vitamin D-deficient chicks to identify genes for novel proteins whose steady
      state mRNA levels are regulated by dietary vitamin D status. In the kidney we
      observed the down-regulated expression of at least seven mitochondrially encoded
      transcripts and the up-regulated expression of five nuclear encoded genes, two of
      which are metallothionein and the beta-subunit of aldolase. In the intestine, six
      mitochondrially encoded transcripts are up-regulated, and seven nuclear encoded
      transcripts were either up- or down-regulated. Thus, in addition to identifying
      new nuclear encoded genes whose mRNAs are regulated by vitamin D status, our
      approach has demonstrated the tissue-specific regulation of mitochondrial gene
      expression in the intestine and kidney.

PMID- 7588304
TI  - Lipopolysaccharide inhibits rat ovarian thecal-interstitial cell steroid
      secretion in vitro.
AB  - Lipopolysaccharide (LPS), a major component of gram-negative cell walls, is a
      potent immunostimulator. Treatment of monocytes/macrophages in vitro with LPS
      induces the secretion of cytokines such as tumor necrosis factor-alpha and
      interleukin-1 alpha, -1 beta, and -6. LPS is thought to require LPS-binding
      protein or CD14 to act at low concentrations (< 100 ng LPS/ml). In the present
      study, rat ovarian thecal-interstitial cells (TIC) were cultured in a serum-free
      culture system (in the absence of LPS-binding protein or soluble CD14) and
      challenged with LPS. Treatment with LPS led to a dose-dependent (1-100 ng LPS/ml)
      decrease in LH-stimulated progesterone and androstenedione secretion. LPS had no
      effect on radiolabeled hCG binding to TIC homogenates or cAMP accumulation in
      culture medium. LPS treatment was associated with an increase in interleukin-6
      bioactivity in the medium of thecal-interstitial cell cultures; however, tumor
      necrosis factor-alpha bioactivity was undetectable. Herbimycin A, an src tyrosine
      kinase inhibitor, blocked the actions of LPS and was associated with an increase
      in cAMP accumulation in TIC culture medium. The results suggest that LPS can act
      directly on ovarian thecal-interstitial cells and that this can occur in a LPS
      binding protein/CD14-independent manner. The actions of LPS appear to be specific
      and require a nonreceptor tyrosine kinase.

PMID- 7588305
TI  - Inhibitory effects of superoxide dismutase and cyclic guanosine 3',5'
      monophosphate on estrogen production in cultured rat granulosa cells.
AB  - Superoxide dismutases (SOD) modulate oxygen free radical metabolism and influence
      second messenger signaling in a variety of cell types. We have investigated the
      influence and possible mechanisms of action of SOD on aromatase activity in
      cultured rat granulosa cells. Although treatment of granulosa cells with FSH (0.3
      30 ng/ml) resulted in a dose-dependent stimulation of estrogen levels,
      cotreatment of cells with SOD (10(-6) M) significantly attenuated estrogen
      production at the highest doses of FSH. The effects of SOD were dose dependent
      between 10(-7)-10(-5) M, with increasing amounts of SOD causing decreasing
      concentrations of estrogen. Cotreatment of cells with catalase (1500 U/ml) failed
      to prevent the inhibitory influence of SOD on estrogen production, indicating
      that the effects of SOD were not due to accumulation of hydrogen peroxide.
      Although incubation with either forskolin or (Bu)2cAMP alone stimulated estrogen
      production from granulosa cells, cotreatment with SOD significantly attenuated
      estrogen levels, indicating that SOD can inhibit aromatase activity at one or
      more post-FSH receptor sites. Treatment of cells with SOD, FSH, or forskolin
      resulted in small, but significant, increase in cGMP concentrations. In contrast,
      cotreatment of cells with FSH plus SOD as well as forskolin plus SOD had a marked
      synergistic effect on cGMP content, increasing cGMP levels over 100-fold.
      Incubation of granulosa cells with (Bu)2cGMP (2 mM) significantly decreased FSH
      induced estrogen levels in a dose-dependent manner (0.25-2 mM). In addition,
      (Bu)2cGMP attenuated both forskolin- and (Bu)2cAMP-induced estrogen production.
      In contrast to the effects of (Bu)2cGMP and SOD on estradiol levels, these agents
      had no significant effect on progesterone production by cultured granulosa cells.
      These results demonstrate attenuated induction of aromatase activity by FSH in
      cultured rat granulosa cells cotreated with SOD, suggesting a potential
      modulatory role of this antioxidant on granulosa cell functions. The findings
      that SOD and activators of the cAMP-dependent signaling pathway synergistically
      increase the levels of the second messenger cGMP and that (Bu)2cGMP treatment
      attenuates FSH-, forskolin-, and cAMP-induced aromatase activity suggest a
      potential mechanism of SOD action and demonstrate the antagonist action of cGMP
      on cAMP-mediated estrogen production.

PMID- 7588308
TI  - Apolipoprotein A-I stimulates placental lactogen expression by human trophoblast
      cells.
AB  - Earlier studies from our laboratory indicated that apolipoprotein A-I (Apo A-I)
      stimulates the acute release of human placental lactogen (hPL) from trophoblast
      cells in culture. We have now demonstrated that Apo A-I also causes a secondary
      increase in hPL release, beginning about 6 h after exposure to Apo A-I, that is
      blocked by cycloheximide and actinomycin D. Apo A-I also stimulated a dose
      dependent increase in hPL promoter activity in JAR cells transfected with a 1.1
      kilobase (-1078/2) fragment of the hPL3 promoter coupled to a chloramphenicol
      acetyltransferase (CAT) reporter gene. Maximal stimulation, 5.2-fold above basal
      levels, occurred at an Apo A-I concentration of 1.5 mg/ml, which is within the
      physiological concentration of Apo A-I during pregnancy. 37pA, a synthetic
      amphipathic peptide that mimics the secondary structure of Apo A-I and stimulates
      the synthesis and release of hPL, also stimulated a dose-dependent increase in
      CAT activity, with maximal stimulation comparable to that caused by Apo A-I. In
      addition, Apo A-I stimulated a modest increase in CAT activity in BeWo
      choriocarcinoma cells, Chinese hamster ovary cells, and HeLa cells. However, the
      maximal stimulation of hPL promoter activity in the Chinese hamster ovary and
      HeLa cells (approximately 2.5-fold above basal levels) was less than that in
      choriocarcinoma cells, suggesting that trophoblast cell nuclear factors may be
      necessary for maximal expression of the promoter in response to Apo A-I. Taken
      together, these results indicate that Apo A-I stimulates hPL gene expression, and
      that DNA elements in the first 1.1 kilobase of the promoter are sufficient for
      transactivation by Apo A-I.

PMID- 7588306
TI  - Developmental increase in low density lipoprotein receptor messenger ribonucleic
      acid levels in placental syncytiotrophoblasts during baboon pregnancy.
AB  - We have previously shown that there was an estrogen-regulated developmental
      increase in low density lipoprotein (LDL) uptake by placental
      syncytiotrophoblasts during baboon pregnancy. To determine whether this reflected
      enhanced expression of the LDL receptor, the levels of LDL receptor messenger RNA
      (mRNA) were determined by Northern blot and reverse transcription-polymerase
      chain reaction in placental tissue obtained from baboons (Papio anubis) in early
      (days 58-64; pooled to yield 5 samples), mid- (days 97-110; pooled to yield 12
      samples), and late (days 161-175; pooled to yield 15 samples) gestation (term =
      184 days). Whole villous tissue and a trophoblast cell fraction isolated by 50%
      Percoll gradient centrifugation were analyzed. The latter cell fraction was
      equally comprised predominantly of syncytiotrophoblasts at early, mid-, and late
      gestation as determined by extensive immunocytochemical reactivity with antisera
      to syncytiotrophoblast-specific peptides. Tissues were extracted with guanidine
      isothiocyanate and 5 micrograms polyadenylated-enriched RNA hybridized to a 32P
      labeled human LDL receptor complementary DNA (cDNA). A major 6.2-kilobase LDL
      receptor mRNA transcript was expressed in syncytiotrophoblasts and whole villous
      tissue, as determined by Northern blot. In the syncytiotrophoblast-rich cell
      fraction, LDL receptor mRNA levels, analyzed by Northern blot and
      autoradiodensitometry and expressed as a ratio of beta-actin, were similarly low
      in early (0.66 +/- 0.12 arbitrary units) and mid- (1.15 +/- 0.23) gestation, then
      increased to a level in late gestation (2.71 +/- 0.33) that was over 4- and 2
      fold greater (P < 0.01) than that in early or midgestation, respectively. In
      contrast, in whole villous tissue, LDL receptor and beta-actin mRNA levels
      exhibited no consistent change or decreased slightly with advancing pregnancy, so
      that when corrected for beta-actin, LDL receptor mRNA levels were similar in
      early (1.53 +/- 0.33), mid- (1.44 +/- 0.16), and late (2.32 +/- 0.29) gestation.
      The unchanged levels of LDL receptor mRNA in whole placental villous tissue with
      advancing primate gestation may reflect potential villous tissue with advancing
      primate gestation may reflect potential confounding effects that nontrophoblast,
      e.g. vascular, components of the developing placenta may have on assessing
      trophoblast endocrine function in whole villous tissue. Amplification of
      trophoblast RNA by reverse transcription-polymerase chain reaction with LDL
      receptor primers generated a single cDNA product of approximately 258 base
      pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588309
TI  - LLC-PK1 cells model 11 beta-hydroxysteroid dehydrogenase type 2 regulation of
      glucocorticoid access to renal mineralocorticoid receptors.
AB  - Mineralocorticoid receptors (MRs) are nonselective in vitro, binding
      corticosterone, cortisol, and aldosterone with similar affinity. In the distal
      nephron in vivo, MRs are selectively activated by aldosterone despite much higher
      glucocorticoid levels. This has been suggested to reflect the action of 11 beta
      hydroxysteroid dehydrogenase (11 beta-HSD), which catalyzes rapid inactivation of
      corticosterone to 11-dehydrocorticosterone (cortisol to cortisone). However,
      cellular models of this effect have not been reported, and a recent study
      suggested that properties intrinsic to MR contribute to aldosterone selectivity.
      We have screened clonal mammalian cell lines for 11 beta-HSD activity. Pig kidney
      epithelial LLC-PK1 cells expressed by far the greatest 11 beta-HSD activity. In
      cell homogenates, this was NAD-dependent, with Km for corticosterone of 34.4 nM
      and cortisol of 89.7 nM. Intact LLC-PK1 cells showed similar apparent Km for
      corticosterone (13.9 nM) and cortisol (79.4 nM); only 11 beta-dehydrogenation was
      detected. These biochemical data indicate the expression of the type 2 isoform,
      11 beta-HSD2. Using primers to conserved regions of 11 beta-HSD2, a reverse
      transcriptase-polymerase chain reaction product was obtained from LLC-PK1 cell
      RNA. Sequence analysis revealed close homology to previously cloned 11 beta-HSD2
      cDNAs from several species. LLC-PK1 cell 11 beta-HSD activity was inhibited by
      carbenoxolone (IC50 approximately 10(-8) M) and high concentrations of estradiol
      or progesterone (10(-7) and 10(-6) M), but was induced at lower estradiol
      concentrations (10(-8) and 10(-9) M). To examine whether the 11 beta-HSD2
      activity in LLC-PK1 cells regulates corticosterone access to MR, cells were
      transfected with the corticosteroid-inducible mouse mammary tumor virus long
      terminal repeat-luciferase reporter construct. Cell transfection by a lipofection
      method did not alter 11 beta-HSD activity in LLC-PK1 cells. LLC-PK1 cells
      expressed low levels of MR (13.9 fmol/mg protein, dissociation constant (Kd) 0.3
      x 10(-9) M for aldosterone) and glucocorticoid receptors (GR; 18.5 fmol/mg
      protein, Kd 0.3 x 10(-9) M for dexamethasone). Transfection with mouse mammary
      tumor virus long terminal repeat-luciferase reporter construct alone suggested
      that the endogenous levels of MR and GR were insufficient to affect
      transcription. However, cotransfection of LLC-PK1 cells with pRShMR, an MR
      expression plasmid, allowed at least 50-fold induction of luciferase with 10(-8)
      M aldosterone; the ED50 0.3 x 10(-9) M closely reflects the in vitro affinity of
      MR for aldosterone. Corticosterone only weakly induced luciferase (maximum of 6
      fold induction).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7588307
TI  - Estradiol inhibits the increase of hypothalamic neuropeptide Y messenger
      ribonucleic acid expression induced by weight loss in ovariectomized rats.
AB  - Anorexia and weight loss produced by estradiol (E2) may involve altered
      expression of neuropeptide Y (NPY) in the hypothalamus. We tested this hypothesis
      using ovariectomized (OVX) rats by replacing E2 with SILASTIC brand capsule
      implants and measuring NPY messenger RNA (mRNA) levels in the arcuate nucleus by
      in situ hybridization. To equalize the effects of weight loss on NPY mRNA
      expression, E2 deficient OVX rats were pair-fed (n = 10) for 2 days to an OVX
      group receiving E2 (n = 12). Compared with the weight gain (P < 0.02) of E2
      deficient OVX rats (n = 10), OVX rats replaced with E2 and pair-fed OVX rats both
      had 12.5% lower food intake and weight (P < 0.05). E2 replacement elevated
      insulin 52% (P < 0.05) and lowered NPY hybridization 32% (P < 0.05) compared with
      pair-fed controls. During a 2-day fast, E2 replacement (N = 12) attenuated the
      elevation of NPY mRNA levels 50% (P < 0.01) compared with E2 deficiency (n = 15).
      Therefore, when E2 is administered to OVX rats, reduced NPY mRNA expression in
      the hypothalamus is unlikely to be a primary cause of weight loss, although it
      may contribute to the maintenance of reduced food intake and body weight.

PMID- 7588310
TI  - Glucocorticoids inhibit D1B, but not D2, receptor-mediated effects on
      hypothalamic atrial natriuretic factor neurons.
AB  - Recent evidence suggests that ANF neurons of the hypothalamus are dopamine
      sensitive, and the catecholamine may exert a direct stimulatory or inhibitory
      effect on the neurons mediated through D1 or D2 receptors, respectively, in a
      manner related to the differential dopamine binding sensitivity of the two
      receptor subtypes. Employing well characterized ANF RIA and colorimetric Northern
      blot analysis with synthetic oligonucleotide probes complementary to pro-ANF
      messenger RNA (mRNA), we report here the effect of dexamethasone (DM), a potent
      synthetic glucocorticoid, on DA-stimulated ANF neurons in long term primary
      cultures of neonatal rat hypothalamic cells. Although DM alone did not affect
      basal secretion of immunoreactive ANF, it approximately halved immunoreactive ANF
      secretion induced by D1 agonist, SKF38393 (P < 0.01). The effect of DM was both
      time dependent and dose related, with an EC50 of 0.1 nM; it was blocked by 100 nM
      RU38486 (P < 0.05), a glucocorticoid receptor antagonist, but not by 100 nM
      RU28318, a mineralocorticoid receptor antagonist. In addition, the effect of DM
      was mimicked by corticosterone (EC50, 10 nM), but not deoxycorticosterone. The
      increased expression of pro-ANF mRNA signal induced by the D1 agonist in culture
      was suppressed by DM in a similar manner. In contrast, DM did not modulate ANF
      production and secretion induced by D2 agonist, quinpirole. Furthermore, reverse
      transcription-polymerase chain reaction demonstrated that D1B, but not D2,
      receptor mRNA expression was selectively suppressed by glucocorticoids. Thus, we
      conclude that in monolayer cultures of rat hypothalamic neurons, glucocorticoids
      differentially modulate dopamine receptor-induced responsiveness of ANF neurons
      by down-regulating D1B, but not D2, receptor-mediated changes. Hence, in severe
      stress, high levels of circulating glucocorticoids may negate the D1B-induced
      stimulatory response but allow dopamine to suppress the function of hypothalamic
      ANF neurons through D2 receptor activation.

PMID- 7588312
TI  - Long-term consequences in offspring of diabetes in pregnancy: studies with
      syngeneic islet-transplanted streptozotocin-diabetic rats.
AB  - To study the long-term effects of exposure to maternal hyperglycemia and insulin
      deficiency in utero, we used the syngeneic islet transplanted streptozotocin
      diabetic rat model of diabetes in pregnancy and examined insulin secretion and
      action in 6-month-old offspring. Female rats were rendered diabetic with
      streptozotocin and then transplanted with 2500, 750, or 500 islets. Control
      animals were also studied, and one group whose islet transplants failed remained
      diabetic. During pregnancy, plasma glucose levels in the diabetic rats and the
      groups receiving 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/-
      0.5 mmol/liter, respectively, all significantly greater than the control value
      (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet
      group was 6.2 +/- 0.2 mmol/liter, which was not significantly higher than the
      control value. When the offspring were studied at 6 months, there was no
      significant difference between groups in either glucose or insulin levels after
      iv glucose, although acute insulin secretion tended to be higher in the offspring
      of the diabetic animals. A study of insulin action with the euglycemic clamp at
      two insulin levels showed that insulin sensitivity was reduced in the offspring
      of diabetic animals vs. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mumol/liter x
      100/kg/min.pmol/liter; P < 0.05). Insulin sensitivity was also significantly
      reduced in the 2500, 750, and 500 islet group offspring (4.81 +/- 0.57, 4.82 +/-
      0.64, and 4.01 +/- 0.63 mumol/liter x 100/kg/min.pmol/liter; P < 0.05) compared
      to that in the control. There were no differences in insulin sensitivity between
      male and female animals. In summary, animals displaying maternal insulin
      deficiency have offspring who are insulin resistant without any evidence of iv
      glucose intolerance or diminished insulin secretion.

PMID- 7588311
TI  - Different 5'-flanking regions of the inhibin-alpha gene target transgenes to the
      gonad and adrenal in an age-dependent manner in transgenic mice.
AB  - The inhibin-alpha gene is expressed in a tissue-specific manner, and its protein
      product dimerizes with one of two beta-subunits to form bioactive heterodimers.
      To characterize the cis-acting elements involved in directing gonad- and adrenal
      specific expression of inhibin-alpha, transgenic mice were generated that carried
      2.5 or 6 kilobases (kb) of the 5'-flanking region of the mouse inhibin-alpha gene
      driving the human bcl-2 complementary DNA. Using an antibody specific for human
      Bcl-2, Western blotting and immunocytochemical analyses showed that both
      enhancer/promoter fragments direct transgene expression to the ovary, testis, and
      adrenal gland. The 6-kb fragment targeted the ovarian transgene expression in
      interstitial cells and young corpora lutea as well as granulosa and thecal cells
      of secondary, antral, and preovulatory follicles. In ovaries of animals with the
      2.5-kb fragment, transgene expression was also detected in interstitial cells and
      young corpora lutea, but only in granulosa and thecal cells from antral and
      preovulatory follicles. The ovarian transgene expression in animals carrying the
      6-kb inhibin-alpha promoter/bcl-2 construct was stimulated by gonadotropin
      treatment, with greater than 10-fold increases observed 2 days after PMSG
      stimulation. In the testes of both types of transgenic animals, immunoreactive
      Bcl-2 was predominantly detected in Sertoli cells of seminiferous tubules.
      Sporadic expression was also observed in some interstitial cells. In the adrenal
      gland, reporter protein was detected in the zona fasciculata of both types of
      transgenic animals during adult life; however, transgene expression was detected
      in zona fasciculata of young (21-day-old) animals with the 6-kb, but not the 2.5
      kb, promoter construct. Thus, the 2.5-kb inhibin-alpha 5'-proximal DNA sequence
      directs transgene expression in mature ovarian follicles and testicular Sertoli
      cells. In contrast, enhancer elements in the 6-kb fragment are required for
      expression in preantral follicles and in the adrenal of immature animals. The
      inhibin-alpha promoter/enhancer used here represents unique DNA sequences for
      ovarian-specific transgene expression and is useful for future analysis of
      gonadal and adrenal cell functions.

PMID- 7588315
TI  - Restraint stress enhances the gene expression of prolactin receptor long form at
      the choroid plexus.
AB  - Hormonal control of brain functions is considered to be important in the
      tolerance of stress, and it is now established that stress elevates serum PRL
      levels in male or cycling female rats. To investigate whether or how serum PRL
      acts on the brain during exposure to stress, we analyzed serum PRL levels and the
      gene expression of brain PRL receptors in rats subjected to restraint stress in
      the water (RSW). The serum PRL concentration was remarkably increased within 30
      min in the rats by exposure to RSW and decreased to the initial level after 4 h
      of RSW, remaining at this level for up to 7 h of RSW. After the rats were
      released from the stress, the serum PRL level was significantly lowered in 6 h.
      Ribonuclease protection assay and in situ hybridization analysis revealed that
      messenger RNA (mRNA) expression for the long form PRL receptor [PRL-R(L)] was
      remarkably induced in the rat choroid plexus in 2 h of RSW. The high expression
      level of PRL-R(L) mRNA in the region was reduced after the rats were released
      from the stress. PRL-R(L) mRNA expression in the hypothalamus was at lower levels
      than those in the choroid plexus before and during the RSW treatment. The short
      form PRL receptor mRNA expression in the rat brain was considerably lower than
      expression of the long form receptor mRNA before or during RSW. The results
      indicated that the restraint stress caused a rapid increase in serum PRL and
      induced the gene expression for PRL-R(L) in the choroid plexus, suggesting stress
      induced and choroid plexus PRL-R(L)-mediated transport of serum PRL into the
      cerebrospinal fluid.

PMID- 7588314
TI  - Sequence analysis of hypothalamic parathyroid hormone messenger ribonucleic acid.
AB  - PTH-like peptides and messenger RNA (mRNA) have recently been detected in neural
      tissues, but it is uncertain whether this reflects the transcription of the PTH
      gene or that of a closely related gene. This possibility has, therefore, been
      investigated. PTH-like complementary DNA (cDNA) moieties of predicted size were
      readily generated from reverse transcribed brain (hypothalamic and
      extrahypothalamic tissue) and pituitary RNA, using polymerase chain reaction
      (PCR) with three sets of overlapping oligonucleotide primers designed to amplify
      PTH cDNA fragments of 285, 372, and 459 base pairs (bp). PCR reamplification of
      the largest hypothalamic moiety with an internal set of primers also generated a
      cDNA fragment of the predicted size (372 bp). Restriction endonuclease digestion
      with BstNI cleaved the largest hypothalamic cDNA moieties into smaller fragments
      of 217 and 242 bp, identical to the cleavage of parathyroidal PTH cDNA. Rapid
      amplification of cDNA ends of the 3'-flanking cDNA sequences also produced
      hypothalamic and extra-hypothalamic cDNA moieties identical in size (499 bp) to
      parathyroidal PTH cDNA. Southern analysis of these PCR and rapid amplification of
      cDNA end cDNA fragments further indicated homology with PTH cDNA. This homology
      was subsequently confirmed by nucleotide sequencing, which demonstrated complete
      homology between the neural and parathyroidal cDNA fragments. This homology
      extended over 673 bp (spanning nucleotides 31-709 of PTH cDNA), encompassing 95%
      of the entire parathyroidal PTH cDNA. The mRNA for this gene, determined by
      Northern blotting with a riboprobe for PTH mRNA, was of identical size to the
      parathyroidal PTH, but its abundance in brain was less than 0.01% of that
      expressed in the parathyroid glands. This transcript was not, however, detected
      in liver. The translation of this moiety in hypothalamic tissues was indicated by
      the presence of a protein in the rat hypothalamus that was immunoreactive with
      PTH-(1-84) antiserum and of comparable size to that in parathyroidal tissue. The
      abundance of this protein in hypothalamic tissue was approximately 0.25% of that
      in the parathyroid glands, suggesting tissue-specific differences in its rate of
      synthesis, processing, or degradation. These results, therefore, demonstrate that
      the brain is an extraparathyroidal site of PTH gene expression and suggest
      autocrine or paracrine roles for PTH in neural function.

PMID- 7588313
TI  - Stereospecific effects of fatty acids on proglucagon-derived peptide secretion in
      fetal rat intestinal cultures.
AB  - The ingestion of fats is a potent stimulus for the secretion of the proglucagon
      derived peptides (PGDPs), including the insulinotropic peptide glucagon-like
      peptide-1 from the intestinal L cell. The aim of the study was to characterize
      the structural requirements for fatty acid-induced secretion of the PGDPs and
      investigate the cellular mechanisms through which fatty acids mediate PGDP
      secretion. Fetal rat intestinal cell cultures were incubated with 10-150 microM
      fatty acids that differed in chain length (14-18 carbons) and degree of
      unsaturation (0-2). Inhibitors of protein kinase C (PKC) and fatty acid
      esterification and oxidation were also incubated with the cells in the presence
      of stimulatory fatty acids. The cultures were assayed for glucagon-like
      immunoreactivity and glucagon-like peptide-1-(7-36)NH2 secretion. Monounsaturated
      fatty acids of chain length greater than 14 carbons stimulated PGDP secretion by
      1.8 to 3.4-fold in a dose-dependent fashion (P < 0.05 to P < 0.001). Enhanced
      PGDP secretion was lost upon full saturation of the stimulatory fatty acids.
      Furthermore, although blockade of fatty acid esterification with a carboxyl
      methyl ester group prevented PGDP secretion, inhibition of fatty acid oxidation
      with methyl palmoxirate did not prevent PGDP secretion. Finally, the use of
      various inhibitors of PKC (staurosporine, H7, 24-h down-regulation) also did not
      alter fatty acid-induced PGDP secretion. In conclusion, monounsaturated long
      chain fatty acids possessing a free carboxyl group stimulate intestinal PGDP
      secretion. Neither fatty acid oxidation nor classical isoforms of PKC appear to
      be directly involved in this response. Therefore, the structure of the fatty acid
      plays a central role in inducing intestinal PGDP secretion. These findings
      suggest that fat composition may significantly affect the magnitude of the GLP-1
      response to ingested nutrients.

PMID- 7588316
TI  - Anti-mullerian hormone and anti-mullerian hormone type II receptor messenger
      ribonucleic acid expression during postnatal testis development and in the adult
      testis of the rat.
AB  - Anti-mullerian hormone (AMH) induces degeneration of the mullerian ducts during
      male sex differentiation and may have additional functions concerning gonadal
      development. In the immature rat testis, there is a marked developmental increase
      in AMH type II receptor (AMHRII) messenger RNA (mRNA) expression in Sertoli
      cells, concomitant with the initiation of spermatogenesis. AMHRII mRNA is also
      expressed at a high level in Sertoli cells in adult rats. To obtain information
      about the possible functions of AMH in the testis, we investigated the postnatal
      expression patterns of the genes encoding AMH and AMHRII in the rat testis in
      more detail. Using RNase protection assays, AMH and AMHRII mRNA expression was
      measured in total RNA preparations from testes or testicular tubule segments
      isolated from control rats and from rats that had received various treatments.
      The testicular level of AMHRII mRNA was found to be much higher than that of AMH
      mRNA in adult rats. AMH mRNA was detected at a maximal level at stage VII of the
      spermatogenic cycle and at a low level at the other stages. AMHRII mRNA increases
      from stage XIII, is highest at stages VI and VII, and then rapidly declines at
      stage VIII to almost undetectable levels at stages IX-XII. It was found that the
      increase in testicular AMHRII mRNA expression during the first 3 weeks of
      postnatal development also occurs in sterile rats (prenatally irradiated), and
      hence, is independent of the presence or absence of germ cells. Yet, the total
      testicular level of AMHRII mRNA was decreased in sterile adult rats (prenatally
      irradiated or experimental cryptorchidism), as compared with intact control rats.
      However, treatment of adult rats with methoxyacetic acid or hydroxyurea, which
      resulted in partial germ cell depletion, had no effect on total testicular AMHRII
      mRNA expression. We conclude that a combination of multiple spermatogenic cycle
      events, possibly involving changes of Sertoli cell structure and/or Sertoli cell
      basal membrane interactions, regulate autocrine AMH action on Sertoli cells, in
      particular at stage VII of the spermatogenic cycle.

PMID- 7588318
TI  - Identification and characterization of a neuroendocrine-specific 5'-regulatory
      region of the human chromogranin A gene.
AB  - Chromogranin A (CgA) expression is specific to cells of endocrine and
      neuroendocrine (NE) tissues. Our transfection studies with CgA have identified
      two DNA regions 5' of the transcription start site that regulate CgA gene
      transcription: a distal regulatory region (DRR) located between -726 and -455,
      and a proximal regulatory region (PRR) between -60 and -26. In studies of the DRR
      using four human NE and six human non-NE cell lines, we demonstrated enhanced
      transcription of DRR-containing CgA-GH plasmids by the NE cells as a group
      compared to the non-NE cells. DNase I footprinting identified a protected area in
      the DRR from -570 to -555 base pairs (bp) composed of the sequence
      TAATGATGACTAAACA. Centered in this sequence is the simian virus 40 version of the
      activator protein-1-binding site, TGACTAA. Electrophoretic mobility shift assays
      (EMSAs) with an oligonucleotide containing the 27 bp of the DRR between -576 and 
      550, which we refer to as the distal regulatory element (DRE), produced a
      specific complex with the NE BEN and non-NE COS-1 cell nuclear extracts. The
      addition of c-Jun and c-Fos antibodies produced strong supershifts of the complex
      generated by COS-1 extract, but very weak supershifts of the complex formed by
      BEN extract. These EMSA studies suggest that NE cells such as BEN contain unique
      nuclear factors distinguishable from activator protein-1 that interact with the
      DRE. The enhancer effect of the 271-bp DRR could be replaced by the 27-bp DRE in
      both CgA and calcitonin promoter constructs in BEN cells. Replacement of the DRR
      with the DRE resulted in a further increase in expression from these plasmids,
      suggesting the presence of suppressor sequences in the DRR. In transfection
      studies of the PRR, deletion of its cAMP response element (CRE) dramatically
      lowered transcription. In addition to demonstrating that its CRE can bind CRE
      binding protein, EMSAs with the PRR demonstrated that an intervening sequence
      between the CRE and the TATA box formed a complex with BEN cell nuclear extract.
      Our studies demonstrate that both the PRR and DRR are important for high level
      transcription of the CgA gene in NE cells. The presence of both distal and
      proximal 5'-regulatory regions in the human CgA gene indicates a complex
      mechanism of transcriptional regulation. Although the PRR is important for the
      formation of a functional transcription complex at the TATA region, the DRR is
      important for the enhancement of CgA gene expression in NE cells.

PMID- 7588317
TI  - Mitochondrial deoxyribonucleic acid content is specifically decreased in adult,
      but not fetal, pancreatic islets of the Goto-Kakizaki rat, a genetic model of
      noninsulin-dependent diabetes.
AB  - Considerable interest has recently been focused on the putative role of mutations
      in the mitochondrial genome for the development of noninsulin-dependent diabetes.
      The Goto-Kakizaki (GK) rat, a genetic model of defective insulin secretion and
      hyperglycemia, is characterized by partial maternal inheritance. Because the
      mitochondrial genome is known to be maternally transmitted, the aim of this study
      was to investigate whether the GK syndrome can be explained in terms of
      alterations of the mitochondrial DNA (mtDNA). For this purpose, pancreatic islets
      were isolated from adult and fetal control Wistar and diabetic GK rats. Using
      electron microscopy, the ultrastructural morphology of beta-cell mitochondria was
      analyzed in control and GK islets. It was found that the beta-cells of adult GK
      rats had a significantly smaller mitochondrial volume and an increased number of
      mitochondria per unit tissue volume as compared with the beta-cells of
      corresponding control islets. Moreover, mtDNA and mtRNA were isolated from the
      islets and, as a control tissue, from liver, and subsequently analyzed using
      Southern and Northern blot techniques. No major deletions or restriction fragment
      polymorphism could be detected in mtDNA from both GK liver and GK islets. The
      mtDNA sequence of the transfer RNAleu(UUS) gene was identical in both strains of
      rats. mtDNA contents of fetal GK islets and fetal GK liver were not different
      from those of fetal Wistar rats. However, adult GK islets contained markedly less
      mtDNA than the corresponding control islets, contrary to the mtDNA contents of
      adult liver, which were similar in the two strains. The lower islet mtDNA
      contents were paralleled by a decreased content of islet mtRNA (12S ribosomal RNA
      and cytochrome b messenger RNA). Islet insulin messenger RNA contents were
      similar in GK and Wistar rats. In conclusion, our results do not support a role
      of a genetic defect in mtDNA as a cause of the GK syndrome. Instead, mtDNA damage
      may occur specifically in islet cells as a consequence of the disturbed metabolic
      environment of the adult GK rat. It is speculated that a long-lasting metabolic
      dysfunction may induce mtDNA damage and/or inhibition of mtDNA replication
      leading to a gradual and late decrease in the mitochondrial volume fraction and
      subsequently an impaired capacity for oxidative metabolism.

PMID- 7588319
TI  - 1,25 dihydroxyvitamin D3 stimulates differentiation of committed murine bone
      marrow-derived macrophage precursor cells.
AB  - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and macrophage colony-stimulating factor
      (M-CSF) both accelerate differentiation of marrow macrophages from which
      osteoclasts are derived. Previously, we showed that the steroid's effect on early
      macrophage precursors may be mediated through M-CSF, as the steroid enhances
      cytokine receptor expression. In contrast, 1,25-(OH)2D3 blunts M-CSF receptor
      expression on more mature, yet still pluripotential, hematopoietic precursors.
      Extending these observations to marrow cells committed to macrophage
      differentiation, we found that 1,25-(OH)2D3 causes a marked decrease in cellular
      proliferation despite a 2- to 3-fold increase in [125I]M-CSF binding in a similar
      dose-dependent metabolite-specific manner. Scatchard analysis demonstrated that
      increased binding reflects increased receptor capacity without an alteration in
      affinity. Steroid-induced M-CSF receptor enhancement reflects acceleration of
      protein appearance rather than overexpression, as treated and untreated cells
      ultimately exhibit equivalent binding. Increased M-CSF receptor expression is
      mirrored by increased c-fms messenger RNA levels, and actinomycin D or
      cycloheximide experiments indicate that new receptor synthesis, rather than
      mobilization of intracellular pools, is required. Thus, 1,25-(OH)2D3
      differentially impacts on M-CSF receptor expression throughout the spectrum of
      bone marrow macrophage differentiation.

PMID- 7588320
TI  - The mineralocorticoid activity of progesterone derivatives depends on the nature
      of the C18 substituent.
AB  - To investigate the role of the C18 substituents in the agonist/antagonist
      properties of mineralocorticoids, the activities of certain C18-substituted
      progesterone (P) derivatives were examined. These compounds were characterized by
      an unsaturated side-chain in the case of 18-vinylprogesterone (18VP) and 18
      ethynylprogesterone (18EP) and by an enone group in the case of 18-oxo-18
      vinylprogesterone (18OVP). P and its 18-substituted derivatives bind to the
      recombinant human MR (hMR) overexpressed in Sf9 cells with the following
      hierarchy of affinity: P > aldosterone > 18VP > 18EP >> 18OVP. Functional
      cotransfection assays in CV-1 cells, using mouse mammary tumor virus promoter as
      a steroid receptor-inducible DNA target sequence, indicated that the
      mineralocorticoid activity depends on the nature of the C18 substituent. 18VP and
      18EP retained the antimineralocorticoid feature of P, with the following order of
      activity: P = 18VP > 18EP. The antagonist potency of 18VP was higher (IC50,
      approximately 10(-8) M) than that of spironolactone (IC50, approximately 7 x 10(
      8) M), the most widely used aldosterone antagonist. Interestingly, introducing an
      oxo function at C18 conferred agonist mineralocorticoid properties; 18OVP behaves
      as a full agonist (ED50, approximately 10(-7) M) with no antagonist activity. In
      contrast to what was observed when the three 18-substituted P derivatives acted
      through hMR, they retained the agonist feature of P through the human P receptor,
      with the following order of potency: P > 18VP = 18OVP > 18EP. The activity of the
      18-substituted P derivatives through the human glucocorticoid receptor was only
      detected at concentrations higher than 10(-6) M; P and 18VP displayed a partial
      antagonist activity, whereas 18OVP had a full agonist activity (ED50,
      approximately 2 x 10(-6) M). Thus, the presence of an oxo group at C18(18OVP)
      does not change the agonist feature of P through human P receptor, but confers to
      the ligand an agonist activity through hMR, suggesting that the C18 carbonyl
      group of aldosterone plays a crucial role in its agonist activity.

PMID- 7588321
TI  - Regulation of retinoblastoma gene expression in hormone-dependent breast cancer.
AB  - Studies have shown an increased risk for breast cancer in the mothers of children
      suffering from retinoblastoma and osteosarcoma, suggesting a role for the
      retinoblastoma susceptibility (Rb) gene product in breast cancer. We now show
      that estradiol decreases the expression of Rb at the level of protein and
      messenger RNA (mRNA) in estrogen-dependent breast cancer cell lines. Treatment of
      MCF-7 cells with 10(-9) M estradiol for 48 h resulted in a 70% decrease in the
      level of Rb protein. Ribonuclease protection assays showed a 50% decrease in the
      steady state levels of Rb mRNA by 12 h and a 70% decrease in Rb mRNA by 24 h.
      Treatment with estradiol had no effect on the rate of Rb gene transcription or on
      Rb mRNA stability, but resulted in an increase in the steady state level of Rb
      mRNA in the nucleus. The effect of estradiol was inhibited by 10(-7) M 4
      hydroxytamoxifen. In the absence of estradiol, the antiestrogens 4
      hydroxytamoxifen and ICI 164,384 increased Rb mRNA by 50% over that in estrogen
      depleted conditions. Estradiol regulation of Rb mRNA also occurred in other
      estrogen-dependent breast cancer cell lines. Insulin-like growth factor I,
      insulin, progestins, and epidermal growth factor had no effect on Rb expression.
      In summary, these results show that estradiol specifically regulates the
      expression of the Rb susceptibility gene product in hormone-dependent breast
      cancer by a posttranscriptional mechanism that occurs in the nucleus. The results
      from this study suggest that the negative regulation of Rb expression by
      estradiol, rather than Rb loss or mutation, may play an important role in breast
      carcinogenesis.

PMID- 7588322
TI  - Assessment of transcript polyadenylation by 3' RACE: the response of epidermal
      growth factor messenger ribonucleic acid to thyroid hormone in the thyroid and
      submaxillary glands.
AB  - The complementary DNA (cDNA) sequence of epidermal growth factor (EGF) indicates
      that its 3' untranslated region (3' UTR) is 745 bases long, with polyadenylation
      occurring at residue 4749. However, when we used reverse transcriptase-polymerase
      chain reaction (RT-PCR) with an anchored 3' primer [3'rapid amplification of cDNA
      ends (RACE)] to amplify the 3' ends of cDNA, we actually detected two major
      products [800 and 600 base pairs (bp)] and a minor product (400 bp) in the
      thyroid or submaxillary glands (SMGs) of male mice. Analysis of genomic DNA with
      a battery of primer pairs gave only the predicted PCR products from the 3' UTR,
      demonstrating the lack of introns in this region of genomic DNA and eliminating
      alternate splicing as the explanation of the transcript diversity we detected. We
      confirmed that two potential polyadenylation sites proximal to residue 4749 are
      used in vivo by hybridizing the same 3' RACE products with probes specific for
      the 5' end of the 3' UTR, and also for poly-A tails. To assess the distribution
      of poly-A tail lengths on transcripts using the terminal polyadenylation site
      (4749), we used several different approaches to analyze 3' RACE products.
      Solution hybridization with 3' UTR probes revealed a striking difference between
      transcripts in SMG and thyroid: SMG contained two large 3' RACE populations
      (approximately 770 and 870 bp), whereas thyroid only contained one (approximately
      770 bp). EGF transcript heterogeneity due to different poly-A tail lengths was
      confirmed using an upstream primer 400 bases closer to the 3' end of the 3' UTR,
      and TaqI digestion. Again we found two major populations in SMG (approximately
      380 and 480 bp), but only one (380 bp) in thyroid, which upon TaqI digestion
      showed tissue-specific heterogeneity only in the 3' fragment. T4 treatment of
      male mice (0.25 microgram T4/gm ip) increased the intensity of both populations
      in SMG and the smaller population in thyroid within 24 h. However, after a week
      of T4 injections, only the intensity of the population with the longer poly-A
      tails in the SMG remained elevated, a finding consistent with tissue-specific
      enhanced stability of transcripts due to polyadenylation. Finally, to resolve
      poly-A tail lengths more precisely, we used an upstream primer that was specific
      for the 3' end of murine 3' UTR. This approach revealed that the thyroid contains
      three major populations of EGF transcripts, with poly-A tail lengths of
      approximately 20, 50, and 70 A's. After T3 treatment for 24 h, the intensity of
      transcripts containing 20 A's increased 52% (P < 0.02) and those with 50 A's
      increased 130% (P < 0.01), whereas there was no change in transcripts with tails
      > or = 70 A's. On the other hand, there were no distinct bands in SMG samples,
      but rather a heterogeneous distribution of poly-A tail lengths from approximately
      20-120 A's that showed an overall increase of approximately 60% in response to
      T3.

PMID- 7588323
TI  - Ca(2+)-regulated expression of steroid hydroxylases in H295R human adrenocortical
      cells.
AB  - Although changes in the expression of key steroidogenic enzymes such as
      cytochrome P450 cholesterol side-chain cleavage, 17 alpha-hydroxylase (P450c17),
      aldosterone synthase, and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in the
      human adrenal cortex are known to be controlled by factors activating the protein
      kinase A or protein kinase C signaling pathways, little is known concerning the
      effects of increased intracellular Ca2+. In this study we describe the effects of
      K+, an agent known to increase intracellular Ca2+ through the opening of voltage
      sensitive Ca2+ channels, on steroidogenesis in H295R human adrenocortical cells
      and corresponding changes in expression of these vital steroidogenic enzymes.
      Treatment of cells for 48 h with K+ (14 mM) resulted in an increase in
      aldosterone (3.5-fold) as well as the 17 alpha-hydroxylated steroids cortisol
      (2.9-fold) and dehydroepiandrosterone (DHEA; 3.7-fold). This action of K+ was
      accompanied by a dose-dependent (P < 0.05 at 6 mM K+ or above) and time-dependent
      (P < 0.05 at 24 h and beyond) increase in expression of P450c17 and, to a lesser
      extent, cytochrome P450 cholesterol side-chain cleavage messenger RNA (mRNA).
      Treatment with K+ also caused a time-dependent increase in aldosterone synthase
      mRNA levels, which were detectable by 12 h. Treatment with K+, however, was
      without effect on 3 beta HSD expression. These effects contrast with those of
      (Bu)2cAMP, which stimulated a greater increase in cortisol and DHEA secretion as
      well as P450c17 expression. The effects of K+ treatment also differ from those of
      AII, which promoted a greater aldosterone secretory response (5.7-fold), but a
      lesser effect on DHEA secretion (2.2-fold) and P450c17 expression. Although AII
      and TPA (known activators of protein kinase C) as well as forskolin and (Bu)2cAMP
      (known activators of protein kinase A) increased the expression of 3 beta HSD
      mRNA, K+ treatment was without effect, suggesting that elevation of [Ca2+]i in
      response to K+ did not activate the protein kinase C or protein kinase A
      signaling pathways. Furthermore, the effects of K+ on steroid secretion and 17
      alpha-hydroxylase activity were reproduced by the voltage-sensitive Ca2+ channel
      activator BAYK 8644, and increases in P450c17 mRNA in response to K+ were
      reversed by the Ca2+ channel antagonist, nifedipine. We conclude that K+ can
      modulate the expression of key steroidogenic enzymes in H295R cells through the
      Ca2+ signaling pathway without involvement of the protein kinase A or protein
      kinase C pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588325
TI  - In vitro characterization of four novel classes of growth hormone-releasing
      peptide.
AB  - Reexamination of the hexapeptide GH-releasing peptide (GHRP-6) structure/function
      has lead to the development of four novel classes of compound that stimulate GH
      release. Each class is represented as follows: a pentapeptide, G-7039; a
      tetrapeptide, G-7134; a pseudotripeptide, G-7502; and a rigid cyclic
      heptapeptide, G-7203. The EC50 values for these compounds, determined by GH dose
      response curves using primary cultures of rat pituitary cells, were 0.18, 0.34,
      10.6, and 0.43 nM, respectively. To demonstrate that these compounds were acting
      at the putative GHRP receptor, challenges were made using combinations that
      included GHRP-6 and GH-releasing hormone (GHRH). All four new classes further
      increased GH release in combination with GHRH, but not with GHRP-6. Homologous
      desensitization occurred after 45 min of exposure to the new compounds while the
      cells remained sensitive to GHRH. Somatostatin inhibited all of these compounds.
      Additionally, G-7039 elevated free calcium, as occurs with GHRP-6. All four
      classes elicited a robust GH release, a small increase in PRL, and no change in
      LH, FSH, ACTH, or TSH. We conclude that these novel compounds are potent and
      direct stimulators of pituitary GH release, with in vitro attributes that suggest
      mediation via a specific GHRP-like mechanism.

PMID- 7588324
TI  - Control of 1,25-dihydroxyvitamin D3 receptor-mediated enhancement of osteocalcin
      gene transcription: effects of perturbing phosphorylation pathways by okadaic
      acid and staurosporine.
AB  - The 1,25-dihydroxyvitamin D3 (vitamin D) receptor (VDR) is a key trans-activating
      protein that mediates calcium regulation as well as cellular proliferation and
      differentiation. Phosphorylation of the VDR contributes significantly to its
      functional activity, but the specific mechanisms that mediate this regulation are
      not well understood. Phosphorylation may influence DNA binding, ligand binding,
      and protein-protein interactions, including heterodimerization and/or
      transactivation functions. We used a protein kinase C inhibitor, staurosporine
      (ST), and an inhibitor of serine-threonine phosphatases, okadaic acid (OA), to
      elucidate the contribution of VDR phosphorylation to vitamin D-mediated
      transcription of the osteocalcin (OC) gene. Vitamin D-induced transcription was
      assayed in transfected ROS 17/2.8 osteosarcoma cells using chloraminphenicol
      acetyltransferase constructs containing the vitamin D-responsive element (VDRE)
      at its native locus in the rat OC promoter as well as fused to a heterologous
      promoter. Both ST and OA inhibit VDRE-mediated and vitamin D-dependent
      enhancement of OC gene transcription as well as OC biosynthesis, as assessed by
      RIAs. Results from gel mobility shift and Western blot analyses using nuclear
      proteins from ROS 17/2.8 cells show that binding of the VDR-retinoid-X receptor
      heterodimer complex to the OC VDRE is not inhibited in the presence of ST. In
      contrast, OA does inhibit the formation of complexes interacting with both the OC
      and osteopontin VDREs; immunoprecipitation studies using 32P-labeled ROS 17/2.8
      cells reveal that OA treatment result in ligand-independent hyperphosphorylation
      of the VDR. Our results suggest that two distinct phosphorylation events modulate
      rat VDR function. One event is related to transactivation, and the other is also
      critical to the VDRE-binding activity of VDR-retinoid X receptor-DNA complexes
      with consequential effects on transactivation.

PMID- 7588326
TI  - Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5
      like transcription factor.
AB  - The cell surface receptors for PRL and interleukin-2 (IL-2) are structurally
      distinct, but share regulatory tasks in T lymphocytes. They can stimulate
      proliferation and activate transcription of over-lapping sets of genes of T
      cells. PRL and IL-2 receptor activation are both linked to the Jak/Stat (signal
      transducer and activator of transcription) pathway. We investigated the ability
      of PRL and IL-2 to activate Stat proteins in different T cell lines. The DNA
      binding specificities, the reactivities toward Stat-specific antisera, and the
      mol wt of IL-2- and PRL-induced DNA-binding proteins in Nb2 and C196 T cell lines
      were investigated. A comparison with the Stat proteins induced by interferon
      gamma, PRL, and IL-6 in T47D mammary tumor cells was made. We found that these
      parameters were indistinguishable for one of the PRL- and IL-2-induced factors. A
      transcription factor closely related to mammary gland factor-Stat5 is rapidly
      activated upon interaction of IL-2 and PRL with their respective receptors.
      Activation of a second protein related to Stat1 was also observed. Our results
      emphasize the role of PRL as a regulator of the immune response and indicate that
      the Stat factors mammary gland factor-Stat5 and Stat1 play a role in the
      regulation of gene expression during T cell development.

PMID- 7588327
TI  - Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type I) and
      BBZ/WORdp (type II) rats with erectile dysfunction.
AB  - Erectile dysfunction occurs frequently in human diabetes, and it is sometimes
      associated with hypogonadism. These conditions also develop in a model of insulin
      dependent (type I) diabetes, the BB/WORdp (diabetic prone) rat but have not yet
      been investigated in the model of insulin-resistant (type II) diabetes, the
      BBZ/WOR rat. It is also unknown whether diabetes-related impotence is due to
      reduced levels of the mediator of penile erection, nitric oxide, caused by a
      decrease of nitric oxide synthase (NOS) in the penis. To clarify these questions,
      groups (n = 5-6) of diabetic BB/WORdp (insulin-maintained) and BBZ/WOR rats were
      age-matched with diabetic-resistant BB/WORdr and non-diabetic BB/WORdp rats and
      submitted to determinations of serum glucose, testosterone, and penile reflexes
      (cups and flips). Erectile dysfunction was found in all of type I and in most of
      type II diabetic animals (glycemias of 25.0 and 31.1 mM), at the selected mean
      ages of 310 and 180 days old, respectively. This was evidenced by over 95%
      decreases of erectile reflexes in both types of diabetes and was accompanied by
      75% reduction of serum testosterone. Soluble NOS activity was measured in penile
      tissue from the diabetic rats with impaired erectile reflexes and in the
      corresponding controls, by the (3H)-L-arginine/citrulline conversion assay. The
      neuronal NOS isoform (nNOS) content was determined by a semiquantitative western
      blot assay. Both types of diabetes showed a marked decrease of penile NOS
      activity (74 and 55%, respectively), and a lower reduction of penile nNOS content
      (47 and 33%, respectively). No endogenous NOS inhibitor was detected in the
      diabetic type I penile cytosol by cross-mixing NOS activity assays. Our data
      support a common etiology for erectile dysfunction present in rats with types I
      and II diabetes mellitus and suggest that the etiology is related to a decrease
      of penile NOS derived in part from serum androgen deficiency.

PMID- 7588328
TI  - Insulin and insulin-like growth factor II suppress neuropeptide Y release from
      the nerve terminals in the paraventricular nucleus: a putative hypothalamic site
      for energy homeostasis.
AB  - It has been recently recognized that a distinct signaling pathway in the
      hypothalamus is involved in the stimulation of feeding in mammals. Neuropeptide Y
      (NPY), a member of the pancreatic polypeptide family, is the most potent
      orexigenic signal, and its secretion in discrete hypothalamic sites increases in
      response to insulinopenia produced by food deprivation or experimental diabetes.
      To establish the site of interaction between the hypothalamus and the pancreas,
      we examined the effects of insulin on NPY release in vivo and in vitro from
      hypothalamic sites known to be involved in feeding behavior. In the first study
      we evaluated the effects of peripheral insulin injections (1 U/kg.day, sc) on NPY
      levels in seven hypothalamic nuclei in food-deprived (FD) and ad libitum-fed
      rats. Whereas food deprivation for 3 days increased NPY levels in the medial
      preoptic area, paraventricular nucleus (PVN), and arcuate nucleus, insulin
      injections, which did not alter blood glucose levels, returned NPY levels to the
      control range selectively in the PVN. NPY levels in the hypothalamic nuclei
      remained unchanged after insulin injections in ad libitum-fed rats. The in vivo
      NPY release in the PVN of FD rats, evaluated by the push-pull cannula technique,
      also decreased in response to peripheral insulin injections. Finally, the effects
      of insulin, insulin-like growth factor I (IGF-I), and IGF-II on NPY release in
      vitro from the microdissected PVN and two central neighboring sites, the
      ventromedial nucleus and the median eminence-arcuate nucleus, of FD rats were
      evaluated. Both insulin (0.67 or 6.7 nM) and IGF-II (0.7 or 7.0 nM) decreased the
      release of NPY in a dose-dependent manner only from the PVN. On the other hand,
      IGF-I (0.07 or 7.0 nM) failed to alter the basal PVN NPY efflux. As the PVN is
      richly innervated by NPY-containing nerve terminals, the results of these in vivo
      and in vitro studies suggest that the site of insulin action on the hypothalamic
      NPY network may reside at the level of PVN nerve terminals or at the interneurons
      in contact with NPY nerve terminals. Although insulin may have a direct effect in
      reducing NPY release from the PVN, the effectiveness of IGF-II in decreasing NPY
      release from the PVN raises the possibility that insulin's action may also be
      mediated via hypothalamic IGF-II neuronal pathways.

PMID- 7588329
TI  - Distinct effects of glucose on the synchronous oscillations of insulin release
      and cytoplasmic Ca2+ concentration measured simultaneously in single mouse
      islets.
AB  - There exists a good temporal correlation between the oscillations of cytoplasmic
      Ca2+ ([Ca2+]i) in pancreatic B cells and insulin release. Here, single mouse
      islets loaded with fura-2 were used to investigate whether there also exists a
      quantitative correlation between both events during stimulation by different
      glucose concentrations. The frequency of [Ca2+]i oscillations was decreased by
      raising the CaCl2 concentration to 10 mM in the perifusion medium (to ensure
      adequate resolution of insulin oscillations by the immunoassay), and the glucose
      concentration was increased from 10 to 20 or from 15 to 30 mM. Raising the
      glucose level was followed by changes in [Ca2+]i oscillations. Their duration
      increased slightly, and that of the intervals decreased, whereas the nadir
      between the oscillations became less deep. On the other hand, the peak of [Ca2+]i
      oscillations did not change. As a result, the rhythm was accelerated, and the
      average [Ca2+]i was increased. The concomitant increase in insulin release
      resulted from similar changes, with, in addition, a marked increase in the peak
      of insulin oscillations. In two thirds of the islets, variations in the amplitude
      of successive [Ca2+]i oscillations occurred during stimulation with 10 mM glucose
      and disappeared at higher glucose levels. This was due to temporal variations in
      the responsiveness of all regions of the islet, rather than to the existence of
      nonresponsive regions that would be recruited into an active state by high
      glucose. In conclusion, there exists a good temporal correlation between insulin
      and [Ca2+]i oscillations in islets stimulated by various glucose concentrations.
      The quantitative correlation is not as close, indicating that the relationship
      between the two phenomena is nonlinear and supporting previous evidence that
      glucose also increases the efficacy of Ca2+ on secretion. This mechanism, rather
      than the development of a Ca2+ rise in nonresponsive cells, might underlie B cell
      recruitment in intact islets.

PMID- 7588330
TI  - Genetics of the BB rat: association of autoimmune disorders (diabetes, insulitis,
      and thyroiditis) with lymphopenia and major histocompatibility complex class II.
AB  - The BB/Wor rat develops spontaneous autoimmune diabetes mellitus and also
      frequently develops lymphocytic thyroiditis. To clarify the role of T cell
      lymphopenia and the major histocompatibility complex (MHC) in the development of
      these autoimmune disorders, we studied back-cross animals between the inbred
      thyroiditis and diabetes-prone BBNB/Wor subline (MHC RT1.AuBuDuCu) and three
      nonlymphopenic MHC-congenic rat strains: PVG.RT.1u (RT1.AuBuDuCu), PVG.R8
      (RT1.AaBuDuCu), and PVG.R23 (RT1.AuBaDaCav1). We observed that 1) lymphopenia is
      absolutely required for the development of spontaneous diabetes and insulitis,
      and is usually associated with the development of thyroiditis; 2) the MHC region
      to the right of the class I RT1.A locus is strongly correlated with diabetes and
      insulitis; and 3) this region is also significantly associated with the
      development of thyroiditis, but the susceptibility of certain MHC class II
      alleles (u and a) for disease development is distinct for insulitis and
      thyroiditis. Furthermore, no recombination was observed between lymphopenia (lyp)
      and the neuropeptide Y (Npy) gene polymorphism, which confirmed that lyp maps
      very close to Npy. The present data suggest that spontaneous insulitis and
      thyroiditis in the BB/Wor rat develop through common immune defects involving T
      cell lymphopenia, but do not always segregate together due to disease-specific
      interactions with the MHC class II-linked genes.

PMID- 7588333
TI  - Targeting simian virus 40 T antigen to the osteoclast in transgenic mice causes
      osteoclast tumors and transformation and apoptosis of osteoclasts.
AB  - Osteoclasts are terminally differentiated cells that express tartrate-resistant
      acid phosphatase (TRAP) at a higher level than other normal cells. Therefore, in
      an attempt to develop immortalized osteoclasts, we produced two lines of
      transgenic mice in which expression of the simian virus 40 T antigen oncogene was
      targeted to osteoclasts using the TRAP gene promoter. Osteoclasts were increased
      in number in bones from both lines. More than 50% of them appeared
      morphologically transformed, 2-5% were mitotic, but, unexpectedly, 5% were
      apoptotic. Osteoclast tumors were observed occasionally in one line of mice (line
      4), and sheets of TRAP-positive cells (tumorlets) developed in most mice in both
      lines. Although cells isolated from these tumorlets formed multinucleated TRAP
      positive cells that resorbed bone in vitro, to date we have been unable to
      develop an immortalized osteoclast cell line from them. Osteoclasts from one line
      (line 5) had reduced ruffled border formation and a higher level of T-antigen
      expression than osteoclasts in the other line (line 4), and these features were
      associated with the presence of osteopetrosis. However, osteoclasts from these
      osteopetrotic mice and from line 4 mice resorbed bone normally when the mice were
      treated with interleukin-1. These findings indicate that T antigen can be
      targeted to osteoclasts in transgenic mice and causes osteoclast transformation,
      tumors, mitosis, and apoptosis. When T antigen is expressed at high levels,
      functional impairment of osteoclasts can be detected. Furthermore, these results
      suggest that T antigen is insufficient on its own to immortalize cells in the
      osteoclast lineage.

PMID- 7588332
TI  - Stress-induced intracranial mast cell degranulation: a corticotropin-releasing
      hormone-mediated effect.
AB  - Stress is known to precipitate or worsen a number of disorders, such as
      migraines, in which mast cells are suspected of being involved by releasing
      vasoactive, nociceptive, and proinflammatory mediators. However, no functional
      association has been demonstrated yet between a migraine trigger and brain mast
      cell activation. Nontraumatic immobilization (restrain) stress has been shown to
      stimulate the hypothalamic-pituitary-adrenal axis and to cause redistribution of
      immune cells. Here, restrain stress caused degranulation in 70% of rat dura mast
      cells within 30 min, as shown both by light and electron microscopy. These
      morphologic findings were accompanied by cerebrospinal fluid elevation of rat
      mast cell protease I, but not II, indicating secretion from connective tissue
      type mast cells. Mast cell activation due to stress was abolished in animals that
      had been treated neonatally with capsaicin, indicating that neuropeptides in
      sensory nerve endings are involved in this response. Complete inhibition was also
      achieved by pretreating the animals ip with polyclonal antiserum to CRH. Mast
      cells in the dura were localized close to nerve processes containing substance P,
      but no CRH-positive fibers were identified even though these were found close to
      mast cells in the median eminence. This is the first time that stress is shown to
      activate intracranial mast cells; apparently through the sequential action of CRH
      and sensory neuropeptides. These findings may have implications for the
      pathophysiology and possible therapy of neuroinflammatory disorders such as
      migraines, which are induced or exacerbated by stress.

PMID- 7588334
TI  - The primate ovary contains a population of catecholaminergic neuron-like cells
      expressing nerve growth factor receptors.
AB  - The ovary of humans and nonhuman primates is innervated by sympathetic and
      sensory neurons of the peripheral nervous system. Recent studies demonstrated
      that the density of the sympathetic innervation to the rhesus monkey ovary is
      developmentally regulated, with adult density being attained around the time of
      puberty. In the present study, we used an immunocytochemical approach to obtain
      insights into the cell-cell signaling mechanisms that may contribute to the
      functional maintenance of this innervation. Because sympathetic neurons of the
      peripheral nervous system require target-derived neurotropins for their survival
      and function, experiments were conducted to determine if one of the receptors
      recognized by neurotropins is expressed in fibers innervating the primate ovary.
      A monoclonal antibody to the human low-affinity nerve growth factor (NGF)
      receptor, termed p75 NGFR because of its molecular weight, demonstrated the
      presence of this receptor in nerve fibers innervating the ovarian vasculature,
      interstitial tissue, and developing follicles of the gland. In addition, as shown
      in rodents, p75 NGFR immunoreactivity was detected in nonneuronal, endocrine
      cells of the ovary, specifically the thecal cell layer of developing follicles.
      Unexpectedly, however, the monkey ovary was also found to contain a network of
      small p75 NGFR immunoreactive cells distributed throughout the ovarian medulla
      and cortex. These cells, identified as such by confocal microscopy, had a neural
      like appearance and displayed both neurofilament and neuron-specific enolase
      immunoreactivity. They appeared to be densely interconnected and were seen
      innervating the ovarian vasculature, the thecal cell layer of follicles, and,
      occasionally, primordial follicles. Double immunohistochemical procedures
      demonstrated that a subpopulation of these intraovarian, p75 NGFR-bearing neuron
      like cells are catecholaminergic, as determined by their immunoreactivity to
      antibodies to tyrosine hydroxylase, the rate-limiting enzyme in catecholamine
      biosynthesis. RNA blot hybridization revealed the presence of p75 NGFR messenger
      RNA in the monkey ovary, thus demonstrating the ability of the gland to
      synthesize the receptors. These results demonstrate that the primate ovary
      contains an intrinsic network of neuron-like cells. Because such a neuronal
      network has not been detected in rodents or other non-primate species, it would
      appear that its presence in the primate ovary may have evolutionary significance.

PMID- 7588335
TI  - Stage-specific expression of B cell translocation gene 1 in rat testis.
AB  - B Cell translocation gene 1 (BTG1) is a member of a new family of putative
      antiproliferative factors. They are characterized by their rapid, but transient,
      expression in response to factors that induce growth arrest and subsequent
      differentiation. In immature rat Sertoli cell cultures, BTG1 messenger RNA (mRNA)
      increases rapidly after FSH stimulation. We obtained the full-length coding
      sequence of rat BTG1 complementary DNA for Northern blot analysis and in situ
      hybridization to determine the temporal expression and spatial distribution of
      BTG1 mRNA in the rat testis. Northern analysis of isolated adult germ cells and
      in situ hybridization analysis of adult seminiferous epithelium demonstrated that
      BTG1 expression was first evident in late primary spermatocytes. The level of
      BTG1 mRNA was also elevated in secondary spermatocytes, but was maximal in
      postmeiotic round spermatids where levels were 5 times the background. BTG1 mRNA
      was not detectable in cells in the M phase of meiosis or spermatids undergoing
      nuclear elongation and condensation. The oscillation of BTG1 expression from the
      late prophase of the first meiotic division through spermatozoa release suggests
      BTG1 involvement in spermatogenesis. High levels of BTG1 mRNA at entry into
      terminal spermatid differentiation suggests a role consistent with that proposed
      for the BTG1 family of antiproliferative factors.

PMID- 7588331
TI  - Interleukin-1 beta regulates the expression of a leukocyte type of 12
      lipoxygenase in rat islets and RIN m5F cells.
AB  - The leukocyte type of 12-lipoxygenase (12-LO) may play a role in inflammatory
      reactions in many cell types through the conversion of arachidonic acid to
      proinflammatory eicosanoids that include 12-hydroperoxyeicosatetraenoic acid and
      12-hydroeicosatetraenoic acid. Previous studies demonstrating the presence of a
      functional 12-LO pathway in rat and human pancreatic beta-cells plus the recent
      cloning of a rat leukocyte type of 12-LO allowed us to evaluate whether
      inflammatory cytokines such as interleukin-1 beta (IL-1 beta) can regulate the
      beta-cell 12-LO enzyme pathway, thus providing a potential link between the
      cytotoxic effects of cytokines on pancreatic beta-cells and the proinflammatory
      effects of 12-LO products. We demonstrate that IL-1 beta induces 12-LO protein
      and messenger RNA (mRNA) expression in RIN m5F cells and 12-LO mRNA expression in
      rat islets. RIN m5F cells treated for 16 h with IL-1 beta (25, 50, and 100
      ng/liter) showed a maximal 2-fold increase in the expression of a leukocyte form
      of 12-LO demonstrated by Western blots. A concomitant increase in 12-LO mRNA
      expression was seen at this time point using a highly sensitive competitive
      polymerase chain reaction assay. The increase in mRNA and protein expression was
      preceded by increased 12-LO pathway activity measured by a RIA for 12-S-HETE.
      Separate experiments using purified Sprague-Dawley rat islets also showed
      increased expression of 12-LO mRNA and enzyme activity in response to IL-1 beta.
      These results demonstrate that IL-1 beta can up-regulate 12-LO expression and
      activity in rat beta-cells.

PMID- 7588336
TI  - Regulation of insulin-like growth factor (IGF) binding protein-3 phosphorylation
      by IGF-I.
AB  - Insulin-like growth factor (IGF) action is modulated by six IGF-binding proteins
      (IGFBP-1 to -6). IGFBP-3 is the main IGFBP in serum and is produced by many cell
      types, which can modify it post-translationally to yield glycosylation,
      proteolysis and phosphorylation products. This study investigates the regulation
      of IGFBP-3 phosphorylation by IGF-I in human neonatal skin fibroblasts.
      Fibroblasts were incubated with IGF peptides and 32P-orthophosphate for 4 h, and
      phosphorylated IGFBP-3 (P-IGFBP-3) was immunoprecipitated from the medium and
      analysed by SDS-PAGE. Media collected from parallel experiments without
      radioactivity were assayed for immunoreactive IGFBP-3 (I-IGFBP-3). IGF-I (50
      ng/ml) increased levels of P-IGFBP-3 and I-IGFBP-3 in conditioned medium to 205
      +/- 9% and 198 +/- 10% of control, respectively (n = 5). Stimulation of I-IGFBP-3
      was consistent with IGF-mediated release of cell-associated IGFBP-3, since
      treatment with an IGF-I analogue with reduced affinity for IGFBPs did not
      increase I-IGFBP-3 levels, whereas treatment with an analogue with reduced
      affinity for receptor but normal affinity for binding proteins did. In contrast,
      stimulation of P-IGFBP-3 occurred independently of IGF binding to IGFBP, instead
      requiring interaction of IGF-I with its receptor. While the functional
      significance of IGFBP-3 phosphorylation is unclear, we propose that it plays a
      regulatory role in IGFBP-3 action.

PMID- 7588339
TI  - Efficacy of XeCl-308 excimer laser in fusing hydroxyapatite to seal the root
      apex.
AB  - Sealing the root apex during apical surgery is important for a successful
      outcome. The effect of XeCl-308 nm excimer laser irradiation on the fusion and
      seal of hydroxyapatite to the root apex was tested in extracted human teeth.
      Twenty-four roots of intact single-rooted premolars were instrumented to size 30
      K-file at the apex leaving a patent apical foramen. The apex of each tooth was
      covered with a freshly prepared paste of hydroxyapatite powder mixed with saline.
      The samples were then divided into two groups. In 12 teeth, the apical area was
      irridiated with XeCl-308 nm excimer laser at a fluence of 0.7 J/cm2 for 5 s with
      pulse repetition rate of 25 Hz and a spot size of 0.13 cm2 immediately after the
      hydroxyapatite application. In the other 12 teeth, no laser treatment was
      performed after the hydroxyapatite application. The roots were mounted on a model
      for the detection of radicular leakage of hydrogen peroxide. The hydrogen
      peroxide leakage of each sample was measured and the difference between the test
      groups compared. The ability of the hydroxyapatite plug to prevent hydrogen
      peroxide leakage at the apex was also tested by applying compressed air from the
      triple syringe on the coronal access preparation for 2 min. Apical leakage was
      found in four teeth in the lased group and in eight teeth in the non-plased
      group. However, the difference between the groups was not statistically
      significant. Compressed air applied to the coronal access caused hydrogen
      peroxide leakage in all the teeth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588337
TI  - Formocresol and alternative primary molar pulpotomy medicaments: a review.
AB  - This paper reviews the history, clinical success and concerns regarding the
      safety of formocresol as a primary molar pulpotomy medicament. The alternatives
      to formocresol are discussed and their advantages and disadvantages evaluated.

PMID- 7588338
TI  - Effect of root canal filling materials containing calcium hydroxide on the
      alkalinity of root dentin.
AB  - The effect of root canal filling pastes containing calcium oxide resp. calcium
      hydroxide on the alkalinity of extracted human teeth was investigated using a
      colour indicator (cresol red). An aqueous suspension of calcium hydroxide
      (Pulpdent), which is normally used for temporary root canal filling, most
      consistently produced alkalinity. Removal of the smear layer following
      instrumentation of the root canal led to increased proportion of alkaline
      positive spots in dentinal locations distant from the canal. A clearly smaller
      effect was found with a calcium salicylate cement (Sealapex) and an oil-paste
      (Gangraena Merz), both of which are available for definite root canal fillings.
      Following removal of the smear layer, these hard-setting preparations caused
      moderate alkalinity in dentin adjacent to the canal but no effect was observed in
      locations more distant from the canal. Neither at locations adjacent to nor
      distant from the root canal was alkalinity found when another calcium salicylate
      cement (Apexit) was used. Apparently the release of hydroxyl ions into root
      dentin from calcium hydroxide containing root canal filling materials is not
      solely influenced by the absolute amount of calcium hydroxide, but also depends
      on other ingredients which variably inhibit the release of these ions.

PMID- 7588340
TI  - Pulpal reaction to a dental adhesive in deep human cavities.
AB  - In the last years several dental adhesives have been developed. They are supposed
      to chemically adhere to dentin and a liner to protect the pulp is not used. The
      aim of this study was to compare the short-term pulpal reaction, in an intra
      toothpair study, between a dental adhesive, Scotchbond 2, and a lining system,
      Tubulitec, in combination with P-50 in surface-sealed cavities. Deep buccal
      cavities in 16 human pairs of premolars, 32 teeth, were restored in vivo with a
      light cured composite resin, P-50. To minimize bacterial contamination all
      cavities were treated with a cleanser, Tubulicid, and the cavities were surface
      sealed with temporary cement, Coltosol. One tooth in each pair, the test, was
      treated with Scotchprep Dentin Primer and Scotchbond 2 Light Cure Dental
      Adhesive. In the other tooth in the pair, the control, Tubulitec Primer and Liner
      were used. The teeth were extracted after 6-14 days. The sections were evaluated
      for degree of inflammation and the presence of bacteria. Irrespective of
      treatment of dentin the majority of teeth, 23, including one pulpal exposure,
      revealed no inflammation or a few inflammatory cells. In four test teeth,
      including one pulpal exposure, and two controls, growth of bacteria was found on
      the cavity walls and slight or moderate inflammation was seen in the
      corresponding pulps. In one test and two control teeth slight inflammation was
      seen but no bacteria could be detected. In the absence of bacteria Scotchbond 2
      did not seem to irritate the pulp.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588341
TI  - Cutting ability of an ultrasonic retrograde cavity preparation instrument.
AB  - The aim of this study was to investigate the cutting ability of a working
      ultrasonic instrument designed for surgical endodontic use (Neosonic, Amadent
      Corp, Cherry Hill, NJ, USA). Three designs of tip, designated CT 1 to CT 3 were
      calibrated by measuring their displacement amplitudes in air using light
      microscopy over a range of power settings. Extracted teeth were sectioned
      longitudinally and polished to produce a smooth dentine surface onto which the
      tips were applied for 1 minute over the above range of power settings at a load
      of approximately 20 g. The depth of cut in the dentine surface was measured using
      a two dimensional surface profilometry technique. Results showed that a raising
      of the power setting produced an increase in displacement amplitude and cutting
      ability for all tip designs. This increase was linear, with minimal cutting
      occurring at lower power settings. In conclusion the ultrasonic tips could be
      successfully used to remove dentine, and medium to high power settings optimised
      their efficiency.

PMID- 7588343
TI  - Dental injuries among schoolchildren aged from 6 to 15, in Rennes (France).
AB  - A representative sample of 2020 schoolchildren, aged 6 to 15 years, was randomly
      selected from 85 state and private schools in Rennes and distributed in 10
      groups, according to their age. Type and prevalence of dental injuries were
      determined in each group, using Ellis & Davey's classification, giving rise to a
      subset of 345 subjects. Simple enamel fracture was the predominant injury
      (59.4%), occurring most often on maxillary central incisors. Most time (77.1%),
      the trauma affected only one tooth. Mean prevalence of dental injuries was 13.6%
      from 2020 subjects. Boys showed a higher prevalence than girls (respectively 17%
      and 10.2%), but this difference was only significant for age-groups 12 and 13 (p
      < 0.001) and for the whole group of 6-15 (p < 0.001).

PMID- 7588342
TI  - Long-term coronal leakage of JS Quickfill root fillings with Sealapex and Apexit
      sealers.
AB  - The purpose of this study was to assess long-term coronal leakage in root
      fillings achieved by 2 gutta-percha techniques using 2 calcium hydroxide
      containing sealers. The root canals of 90 single-rooted teeth with mature apices
      were prepared chemomechanically. The teeth were placed randomly into four
      experimental groups (n = 20) and obturated with either lateral condensation of
      cold gutta-percha or a thermo-plasticized gutta-percha delivery system, JS
      Quickfill, using Sealapex or Apexit as the sealer. A further five teeth were
      placed in each of negative or positive control groups. After root filling the
      teeth were sectioned at the cementoenamel junction and stored in saline solution
      at 37 degrees for 1 yr. Coronal leakage was then determined with an India ink
      tracer (using a reduced pressure model) and a clearing technique. The extent of
      coronal leakage was measured at x6 magnification. Non-parametric analysis showed
      that there was significantly more leakage with the thermally softened gutta
      percha technique than with lateral condensation (p < 0.05). There was no
      significant difference in leakage between the groups obturated with lateral
      condensation (p > 0.005) but, with the thermoplasticized technique, there was
      more leakage with the sealer Sealapex (p < 0.05).

PMID- 7588345
TI  - Endodontic management of mandibular lateral incisor fused with supernumerary
      tooth.
AB  - In this article we report a case of a mandibular lateral incisor in which 3
      separate root canals were located. Clinical and radiographic examinations
      suggested that fusion had occurred between the mandibular incisor and a
      supernumerary tooth. The endodontic management of the tooth is described, and
      repair of an apical periodontitis had occurred after 9 months.

PMID- 7588344
TI  - Computerized reconstruction of TEM examined pulpal blood vessels and nerves.
AB  - Five healthy premolars were used for transmission electron microscopy examination
      and three-dimensional (3D) reconstruction of pulpal blood vessels and their
      surrounding nerves. Serial Epon thin sections were taken from specimens. After a
      series of preprocessing steps that included digitization, contrast enhancement,
      slice alignment, segmentation and interpolation, three dimensional surface
      representation was performed using the triangulation method. The findings showed
      that vessels were usually accompanied by a number of myelinated and unmyelinated
      nerves. The nerves shared a more or less common course with the vessels. Small
      arteries presented greater number of nerves in their vicinity, compared to small
      veins. In the sections examined, no direct contact between the nerve trunks and
      the wall of the vessels was found; the closest distance measured was
      approximately 67 microns. The common course of vessels and nerves suggested
      autonomic innervation on part of the myelinated axons.

PMID- 7588346
TI  - Importance of anatomic variables in endodontic treatment outcomes: case report.
AB  - Surgical endodontic treatment was performed after a large periradicular lesion
      failed to resolve following nonsurgical intervention. The subsequent
      periradicular surgery resulted in healing with scar formation. Assessment of the
      resected root apex revealed a complex anatomy. The ramifications of these
      anatomical findings and the periradicular tissue response in healing are
      discussed relative to prognosis and ultimate treatment outcomes.

PMID- 7588347
TI  - Ethanolamine oleate versus butyl cyanoacrylate for bleeding gastric varices: a
      nonrandomized study.
AB  - BACKGROUND AND STUDY AIMS: Sclerotherapy may be useful in patients with bleeding
      gastric varices. The aim of this study was to compare the effects of two
      sclerosants in these patients. PATIENTS AND METHODS: In a prospective
      nonrandomized trial, we performed single sclerotherapy for bleeding gastric
      varices using ethanolamine oleate (n = 24) or butyl cyanoacrylate (n = 29). The
      patients were followed for a mean of 14 months. RESULTS: The rate of initial
      hemostasis (no bleeding occurred for 48 hours after sclerotherapy) was
      significantly higher in the butyl cyanoacrylate group (93%) than in the
      ethanolamine oleate group (67%) (p = 0.014). The rate of initial hemostasis in
      cardiac variceal bleeding did not differ significantly between the ethanolamine
      oleate and butyl cyanoacrylate groups (83% vs. 100%, p = 0.140). In contrast, the
      hemostasis rate for fundal variceal bleeding was significantly higher in the
      butyl cyanoacrylate group than in the ethanolamine oleate group (88% vs. 50%, p =
      0.023). Although the rebleeding rate did not differ between the two groups (30%
      vs. 25%, p = 0.921), the mortality rate was significantly higher in the
      ethanolamine oleate group (67% vs. 38%, p = 0.043). In addition, the incidence of
      complications in the butyl cyanoacrylate group was similar to that in the
      ethanolamine oleate group (46% vs. 41%, p = 0.745). CONCLUSIONS: These results
      suggest that initial control of fundal varices is more difficult than it is with
      cardiac varices, but butyl cyanoacrylate is superior to ethanolamine oleate, and
      the survival advantage from butyl cyanoacrylate seems to be partially related to
      the increased early bleeding deaths in the ethanolamine oleate group.

PMID- 7588350
TI  - Upper endoscopy in patients with angina and normal coronary angiograms.
AB  - BACKGROUND AND STUDY AIMS: It has been recommended that patients with angina, a
      normal coronary angiogram, and no other signs of heart disease, should be
      evaluated using esophagogastroduodenoscopy before referral to dynamic esophageal
      investigations. The aim of the present study was to investigate the clinical
      value of upper endoscopy in this patient group. PATIENTS AND METHODS: Forty-nine
      consecutive patients (28 women aged 18-70 years, mean 51.6 years) with angina
      like chest pain and a normal coronary angiogram, who were referred to a tertiary
      cardiologic center, were included in a prospective study. Upper endoscopy with
      distal esophageal biopsies was performed. The results were compared with 24-hour
      pH monitoring. At a median of 36 months after discharge, the patients were asked
      to complete a follow-up questionnaire. RESULTS: Macroscopic esophagitis was found
      in 15 patients (31%), and microscopic esophagitis in 11 (25% of the patients who
      underwent esophageal biopsy). One patient had macroscopic grade II esophagitis,
      and the rest had grade I esophagitis. The only major abnormalities were three
      peptic ulcers (6%). Five patients had symptoms of gastroesophageal reflux, but
      the 24-hour pH monitoring revealed an abnormal reflux index in only one. The
      median reflux index was 1.3 (range 0.0-13.4) in the patient group and 2.1 (range
      0.0-9.9) in a control group (n = 22; p = 0.49). Patients with positive and normal
      exercise electrocardiography did not differ in terms of the endoscopic findings
      or reflux index. At the post-study follow-up, 38% of the patients had undergone
      acid secretion inhibitor treatment, with an effect on symptoms in only 4%.
      CONCLUSIONS: The study provides evidence that routine esophagogastroduodenoscopy
      is of limited value in this group of patients.

PMID- 7588349
TI  - The value of combined use of N-butyl-2-cyanoacrylate and ethanolamine oleate in
      the management of bleeding esophagogastric varices.
AB  - BACKGROUND AND STUDY AIMS: Recently, tissue adhesive material has been used to
      improve the initial control of bleeding from huge esophagogastric varices, and to
      prevent them from rebleeding, in contrast to the conventional sclerotherapy. The
      present study assessed the value of the combined use of the tissue adhesive
      substance: N-butyl-2-cyanoacrylate and ethanolamine oleate 5% for management of
      bleeding esophagogastric varices. PATIENTS AND METHODS: One hundred and fourteen
      patients with documented active variceal bleeding at the time of endoscopy were
      alternatively randomized into two groups. The combined therapy group included 58
      patients who underwent injection using both cyanoacrylate for large esophageal
      and gastric varices and a sclerosant agent for remaining varices. The sclerosis,
      or control, group included 56 patients, who underwent injection with ethanolamine
      oleate. RESULTS: This study proved the value of the combined therapy for the
      initial control of all bleeders (the follow-up period ranged from 12 to 32
      months). In the sclerosis group, failure of the initial control of bleeding was
      reported in two cases (3.6%). Recurrent bleeding occurred in 8.6% in the combined
      therapy group compared to 25% in the sclerosis group (p < 0.01). Two months of
      therapy was required to achieve complete eradication of varices in 56.5% and
      21.4% in the combined therapy and the sclerosis group, respectively. The mean
      number of sessions needed until the time of evaluation was 2.4 +/- 1.1 in the
      combined therapy group versus 5.1 +/- 2.3 sessions in the sclerosis group. The
      difference showed high statistical significance (p < 0.01). Minor complications
      occurred less frequently in the combined therapy group. Only one patient in the
      combined therapy group developed portal pyemia after extension of the tissue
      adhesive material from the site of injection into the portal vein. This patient
      died of hepatic failure. The mortality in the combined therapy group was lower
      than that in the sclerosis group (3.5% and 8.8% respectively, p > 0.05).
      CONCLUSION: The combined use of tissue adhesive and sclerosant materials seems to
      be the best plan for rapid eradication of esophagogastric varices within a short
      time, requiring the lowest number of injection sessions and involving minor
      complications and low mortality.

PMID- 7588348
TI  - N-butyl-2-cyanoacrylate (Histoacryl) plus sclerotherapy versus sclerotherapy
      alone in the treatment of bleeding esophageal varices: a randomized prospective
      study.
AB  - BACKGROUND AND STUDY AIMS: N-2-cyanoacrylate (Histoacryl) and endoscopic
      sclerotherapy with polidocanol have both been reported to control variceal
      bleeding. The aim of the present study was to compare the effectiveness of the
      combination of Histoacryl and endoscopic sclerotherapy with polidocanol in the
      management of these patients regarding early rebleeding and hospital mortality
      rates. PATIENTS AND METHODS: One hundred twenty-six consecutive patients with
      variceal hemorrhage treated with injection therapy between March 1990 and July
      1993 were included in this randomized prospective study. Sixty-seven patients
      (Group A) were treated with Histoacryl and conventional sclerotherapy with
      polidocanol, and 59 patients (Group B) were treated with conventional
      sclerotherapy with polidocanol alone. Histoacryl was injected intravariceally
      during the first session in the Group A patients. RESULTS: A significantly lower
      bleeding recurrence rate was found in Group A patients who presented with active
      bleeding at the first treatment session (Group A: 2 of 20, Group B: 8 of 18, p <
      0.05). The hospital mortality was also significantly lower in these patients
      (Group A: 3 of 21, Group B: 9 of 18, p < 0.05). CONCLUSIONS: The combination of
      Histoacryl with conventional sclerotherapy with polidocanol in patients with
      esophageal bleeding who present with active bleeding, at the initial injection
      therapy, can improve the results of endoscopic management.

PMID- 7588353
TI  - Dormia baskets impacted in the bile duct: release by extracorporeal shock-wave
      lithotripsy.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic extraction of bile duct stones may be
      complicated by impaction of the Dormia basket with captured stones, or rupture of
      the traction wire of the basket during mechanical lithotripsy. In an attempt to
      release impacted baskets by nonoperative means, we studied the efficacy of
      extracorporeal shock-wave lithotripsy in this dangerous clinical situation.
      PATIENTS AND METHODS: Fourteen extracorporeal shock-wave treatments were
      performed in 12 consecutive patients (eight women and four men; mean age 73.2 +/-
      13.2 years, range 46-86 years) with an electrohydraulic shock-wave lithotriptor,
      using fluoroscopy (n = 13) or ultrasound (n = 1) for targeting. A total of 1845
      +/- 334 (mean +/- SD) shock-wave discharges at a voltage of 22 +/- 4 kV were
      delivered per treatment. Nine treatment sessions (64%) were performed while
      patients were under general anesthesia. An attempt to extract the Dormia basket
      was made after disintegration of the captured stone had been confirmed by
      fluoroscopy. RESULTS: It was possible to remove the Dormia basket by nonsurgical
      means in 11 of the 12 patients (92%) after one treatment session, and after three
      treatment sessions in the remaining patient. Thus, disintegration of the stones
      allowed extraction of the Dormia basket in all patients. None of the patients
      needed surgical intervention. All patients were rendered free of bile duct stones
      after extracorporeal shock-wave lithotripsy and subsequent endoscopic removal of
      the fragments. No adverse effects of shock-wave therapy with subsequent
      extraction of the Dormia baskets were observed. CONCLUSION: Shock-wave therapy
      represents a primary nonsurgical therapeutic option in patients with either
      impacted Dormia baskets or broken devices which cannot be extracted by endoscopic
      means.

PMID- 7588351
TI  - Presumptive clinical criteria versus endoscopy in the diagnosis of Candida
      esophagitis at various HIV-1 disease stages.
AB  - BACKGROUND AND STUDY AIMS: The presumptive diagnosis of Candida esophagitis has
      been included in the Centers for Disease Control (CDC) case definition for full
      blown AIDS since 1987. Endoscopic examination should be reserved for patients
      showing symptoms despite treatment. The purpose of this study was to assess the
      degree of diagnostic accuracy of the CDC presumptive clinical criteria and to
      determine the usefulness of upper digestive endoscopy in the diagnosis of Candida
      esophagitis in patients infected with HIV-1, with and without a previous AIDS
      defining event. PATIENTS AND METHODS: A total of 144 HIV-1 infected patients who
      had undergone an upper digestive endoscopy were studied retrospectively. To
      determine the risk and the predictive value of the clinical markers, only the 84
      patients without prior antimycotic therapy were included. RESULTS: Of the 84
      patients without previous treatment, 34 (41%) had a history of an AIDS-defining
      illness. Candida esophagitis was found on endoscopy in 11 of the AIDS and 28 of
      the non-AIDS cases. Oral thrush, either alone (relative risk [R.R.] 9.4; 95% C.I.
      2.4-36.4; p < 0.01; positive predictive value [PPV] 82%) or in combination with
      esophageal symptoms (R.R. 7.4; 95% C.I. 2.5-21.9; p < 0.01; PPV 89%), was a
      reliable marker of Candida esophagitis only in patients with a previous AIDS
      defining event. The diagnostic value of the CDC presumptive pattern was confirmed
      by a multivariate analysis after controlling for the CD4 cell count (R.R. 9.3;
      95% C.I. 2.3-25.3; p < 0.01). On the other hand, in HIV-1 positive patients
      without a previous AIDS-defining event, the diagnostic accuracy of oral
      candidiasis, either alone (R.R. 1.4; 95% C.I. 0.8-2.4; p n.s.; PPV 64%) or in
      combination with esophageal symptoms (R.R. 1.1; 95% C.I. 0.7-1.8; p n.s.; PPV
      60%), was too low to allow a reliable diagnosis of Candida esophagitis.
      CONCLUSIONS: A presumptive diagnosis of Candida esophagitis on the basis of the
      CDC clinical criteria is a valid diagnostic method only in HIV-1 infected
      patients with a previous diagnosis of full-blown AIDS. Upper digestive endoscopy
      should be performed in symptomatic patients with no history of an AIDS-defining
      illness, especially if the diagnosis of esophageal candidiasis is important for
      surveillance purposes.

PMID- 7588354
TI  - Effects of sphincterotomy on gallbladder physiology: a review.

PMID- 7588352
TI  - Fluconazole vs. flucytosine in the treatment of esophageal candidiasis in AIDS
      patients: a double-blind, placebo-controlled study.
AB  - BACKGROUND AND STUDY AIMS: Contrasting opinions exist as to the pharmacological
      treatment of esophageal candidiasis in human immunodeficiency virus (HIV)
      positive patients. The aim of this study has been to evaluate the role,
      therapeutic efficacy, and the cost-benefit ratio of two antifungal drugs,
      fluconazole and flucytosine, compared with a placebo, in the treatment of
      endoscopically-diagnosed esophageal candidiasis in patients with acquired immune
      deficiency syndrome (AIDS). PATIENTS AND METHODS: The study included 60 HIV
      positive patients (38 males and 22 females, mean age 27 +/- 2) with a first
      episode of esophageal candidiasis diagnosed by endoscopy (grades I-II of Kodsi's
      endoscopic classification, and grades I-IIa of Barbaro's clinical
      classification). No other opportunistic infection of the esophagus was detected.
      In a double-blind procedure, patients were randomized into three groups of 20
      patients each, receiving either fluconazole (3 mg/kg/daily per os), flucytosine
      (100 mg/kg/daily per os) or placebo. After two weeks of treatment, the patients
      previously assigned to receive the placebo were double-blindly randomized to
      receive fluconazole (eight patients) or flucytosine (nine patients). In order to
      evaluate the efficacy of pharmacological therapy, clinical examination was
      performed at weeks 2 and 5, and then every week up to the end of follow-up (three
      months); endoscopic examination was performed at weeks 2 and 5, and at the end of
      follow-up. RESULTS: At week 2, endoscopic cure (grade 0) was observed in 13
      patients (65%) of the fluconazole group and in three patients (15%) in the
      flucytosine group (relative risk ratio: 0.23; 95% C.I.: 0.10-0.48; p < 0.05), and
      a partial endoscopic response (grade I) was observed in two patients (10%) in the
      placebo group. Complete clinical remission (grade 0) was observed in 16 patients
      (80%) in the fluconazole group and 12 patients (60%) in the flucytosine group
      (relative risk ratio: 0.75; 95% C.I.: 0.42-0.89; p = n.s.), while six patients
      (30%) in the placebo group presented partial clinical remission (grade I). At the
      end of follow-up, endoscopic cure was observed in 19 patients (70%) in the
      fluconazole group and in nine patients (33%) in the flucytosine group (relative
      risk ratio: 0.47; 95% C.I.: 0.19-0.65; p < 0.05). Complete clinical remission was
      observed in 21 patients (77.7%) in the fluconazole group and in 17 patients (63%)
      in the flucytosine group (relative risk ratio: 0.81; 95% C.I.: 0.53-0.92; p =
      n.s.). No noticeable side-effects were observed in the patients in either
      treatment group, without a statistically significant difference in comparison
      with the placebo. CONCLUSIONS: The results of this study have demonstrated that
      both fluconazole and flucytosine are safe and well tolerated in the treatment of
      esophageal candidiasis in AIDS patients. Fluconazole showed greater therapeutic
      efficacy than flucytosine, with a difference that was statistically significant
      in terms of the rate of endoscopic cure.

PMID- 7588357
TI  - Three-dimensional reconstruction of the biliary tract from two-dimensional
      biliary images.
AB  - To make conventional two-dimensional cholangiography easier and more precise to
      read, we used techniques in computer vision to reconstruct the images in three
      dimensions. A 72-year-old man and a 70-year-old woman suffering from acute
      cholangitis were treated using endoscopic nasobiliary drainage. Their
      cholangiograms, from two orthogonal views, were used for three-dimensional
      reconstruction. We used video image-grabber and film scanner methods to digitize
      the original conventional biliary radiographs, and applied two different image
      processing methods to show the biliary structure. Both methods of three
      dimensional reconstruction of the biliary tract were highly useful in evaluating
      the biliary tracts in these two patients, especially when a semitranslucence
      overlapping display technique was applied in the second patient. With this
      technique, the biliary tree itself and the stones inside the common bile duct can
      be clearly delineated. The technique of three-dimensional reconstruction of
      biliary images can make the conventional cholangiographs more lifelike and has
      great potential in surgical simulation in the near future.

PMID- 7588355
TI  - "Superglue": the answer to variceal bleeding and fundal varices?

PMID- 7588358
TI  - Atypical presentation of duodenal tuberculosis.

PMID- 7588356
TI  - Primary malignant melanoma of the esophagus presenting with massive hematemesis.
AB  - A 66-year-old Japanese man was admitted to our hospital, presenting with massive
      hematemesis. Emergency endoscopy revealed a bleeding tumor at the esophagogastric
      junction. The endoscopic appearance of the tumor was that of a Borrmann 2-like
      tumor, with a brownish-black discoloration. Bioptic histology confirmed the
      diagnosis of malignant melanoma. Atypical melanocytes with junctional changes
      were also found at a small pigmented patch in the lower esophagus, separate from
      the gross tumor. Melanocytosis was noted in the adjacent esophageal epithelium in
      the resection specimen following surgery. No primary lesion was found elsewhere,
      even in the patient's skin. These pathologic findings support the possibility of
      multicentric occurrence of malignant melanoma in esophageal melanocytosis. The
      patient is alive 11 months later, with multiple liver metastases. Massive
      hematemesis is an unusual presentation of primary malignant melanoma of the
      esophagus.

PMID- 7588359
TI  - A case of diffuse cavernous hemangioma of the rectum with unusual clinical
      manifestations.

PMID- 7588361
TI  - Peroral cholecystoscopy with a shape-memorizing alloy catheter.

PMID- 7588360
TI  - Frequent submucosal migration of soft percutaneous endoscopic gastrostomy
      catheters, and conservative management.

PMID- 7588362
TI  - Endoscopic retrieval of a large gastric foreign body with a home-made fishing
      net.

PMID- 7588363
TI  - Endoscopic diagnosis of malignant melanoma in the gastric cardia--report of a
      case without a detectable primary lesion.

PMID- 7588364
TI  - Afferent loop syndrome due to scarring of a stomal ulcer following a Billroth II
      gastrectomy.

PMID- 7588365
TI  - A simple single endoscopy technique to replace percutaneous endoscopic
      gastrostomy tubes.

PMID- 7588366
TI  - Mucosal dissection and massive hematemesis following gastroduodenal endoscopy and
      biopsy.

PMID- 7588367
TI  - Pancreas divisum imitating malignancy in a patient with a cystadenoma.

PMID- 7588368
TI  - Papers presented at the 6th Conference on the Adrenal Cortex. Ardmore, Oklahoma,
      June 21-24, 1994.

PMID- 7588369
TI  - Zonation, paracrine function and aldosterone secretion in the rat adrenal cortex.
AB  - Using in situ hybridisation we show that, in the rat adrenal, 11 beta-hydroxylase
      is confined to the inner zones, whereas aldosterone synthase is expressed
      exclusively in the glomerulosa. Immunoblotting methods identify an 18
      hydroxydeoxycorticosterone (18-OH-DOC) in IEF gels of solubilised inner
      adrenocortical zone membrane preparations. This steroid, which can also be
      identified by immunocytochemistry, cannot be solvent extracted from the IEF gels
      unless the gel slices are first treated with trypsin. Preincubation of viable
      whole glandular tissue with trypsin significantly enhances aldosterone output,
      and eliminates the trypsin releasable 18-OH-DOC pool in IEF gels. The data
      suggest that 18-OH-DOC is synthesised and sequestered in inner zone cells, in a
      novel non-solvent extractable manner, but can be mobilised for utilisation as an
      aldosterone precursor in the glomerulosa.

PMID- 7588370
TI  - Perspectives in steroid hydroxylase gene expression: novel sites of expression
      during embryonic development.
AB  - CYP17 is not expressed in adult mouse adrenal glands but is expressed in a subset
      of fetal adrenocortical cells, indicating the potential to produce both
      corticosterone and cortisol during murine embryogenesis. CYP11A is expressed in
      the fetal adrenal but also in developing hindgut, which will form the colon, and
      in cells located beneath the skin of the embryo. Novel sites of expression of
      CYP17 and CYP11A in the mouse embryo suggest potential physiological roles for
      local production of steroids in diverse organs systems during development.

PMID- 7588372
TI  - Evidence for fibroblast growth factor mediation of compensatory adrenocortical
      proliferation.
AB  - The role of basic fibroblast growth factor (bFGF) in the neurally mediated
      control of compensatory adrenocortical cell proliferation which occurs in
      response to unilateral adrenalectomy has been investigated. Three isoforms of
      bFGF have been identified in the rat adrenal with Western blots and bFGF
      immunoreactivity is most concentrated in the glomerulosa cells. A high affinity
      binding site (Kd = 10 pM) was identified in primary cultures of rat glomerulosa
      cells. Using autoradiography of 125I-bFGF binding, in vivo bFGF binding sites
      were found concentrated in the glomerulosa as well as the capsule cells. The
      compensatory adrenocortical proliferation was blocked by suramin and bFGF
      receptor density appeared to be regulated during this proliferation. These
      results support a role for bFGF in autocrine and paracrine stimulation of
      proliferation in the adrenal cortex and capsule. To specifically block the
      receptor-mediated effect of bFGF in this response, we have developed an antisense
      strategy. Antisense oligodeoxynucleotide targeted against bFGF-receptor mRNA
      blocks the proliferative effect of bFGF in primary glomerulosa cell cultures by
      approximately 50%. These results indicate that this antisense strategy interferes
      with the expression of bFGF-receptors and is an effective technique to reduce the
      proliferative effect of bFGF via the effect on its receptor.

PMID- 7588371
TI  - Sex differences in the steroidogenic and respiratory electron transport chains in
      the rat adrenal cortex.
AB  - Both steroid 11 beta-hydroxylation and cholesterol side chain cleavage occur in
      the mitochondria of adrenocortical cells and they require reducing power in the
      form of NADPH. There are direct sources of NADPH in rat adrenal mitochondria but
      another potential source of NADPH is the energy-linked transhydrogenase reaction.
      This suggests that there is a relationship between the steroidogenic and
      respiratory chains. We have elaborated upon this relationship by exploring the
      expression of cytochrome c oxidase (CO) and cytochrome P-45011 beta. We have
      studied the regulation of one mitochondrial-encoded (COII) and one nuclear
      encoded (COIV) subunit. Normal, untreated male rats had higher basal levels of
      activity of CO in adrenal (255%) and liver (144%) mitochondria, compared to
      normal, untreated female rats. They also had increased COII (300% and 138%) and
      COIV (300% and 135%). Cytochrome P-45011 beta levels, however, were lower (48%)
      in adrenal mitochondria of male rats than those of female rats. Androgen
      treatment of male rats caused an increase in the activity of CO in the
      mitochondria of the adrenal gland with the levels being 171% of the corresponding
      controls. This increase in activity paralleled an increase in the levels of COII
      and COIV in the adrenal as measured by Western analysis. In contrast, adrenal
      cytochrome P-45011 beta levels were lower (68%). Androgen treatment caused no
      significant change in the levels of mRNA's for COII and COIV whereas cytochrome P
      45011 beta mRNA was significantly lower than normal.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7588374
TI  - The development of the adrenal cortex in the rat. An immunohistochemical study.
AB  - The Inner Zone Antibody (IZAb) is a monoclonal antibody which interacts with an
      antigen found predominantly in rat adrenal inner cortical zones. Since its
      expression increases after ACTH treatment the antigen may have a role in
      steroidogenesis although, so far, this has not yet been fully characterised. Due
      to its molecular weight, it cannot be any of the known cytochrome P450 proteins.
      In this study we examined the expression of IZAb in male and female rats
      throughout their postnatal development and in aged animals. In a different set of
      animals, blood was collected for hormonal assays and the adrenals stained with
      classical methods. The staining with IZAb was clear from the first post-natal
      day. The zona glomerulosa which was always present at birth, was easily
      distinguished and unstained. The staining in the inner zone cells was fainter at
      birth and increased progressively until postnatal day 20. Afterwards these cells
      were remarkably stained at all ages. Medullary cells were also present from birth
      although they were generally found in clusters instead of constituting a well
      defined zone. Cortical cells appeared in the medullary zone at all ages after its
      complete development. The zona glomerulosa increased in size until approximately
      postnatal day 40 while the inner zones increased until day 70. The area of the
      cortex was significantly different between the two sexes from day 50 onwards and
      this was predominantly due to differences in the zona fasciculata. Corticosterone
      levels increased until approximately day 25 in the male rat and until day 45 in
      the female.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588373
TI  - Optimizing ACTH-stimulated steroid secretion by cultured adrenocortical tumor
      cells.
AB  - If 1 mM supplemental Ca++, or 1.6 mg hemoglobin (Hb)/ml medium (23.5 uM, a
      concentration comparable to that in 1 ml mouse blood), was added to Eagle's
      minimum essential medium (MEM) (which contains 1 mM Ca++), basal and maximally
      stimulated 20-dihydroprogesterone (20-DHP) secretion by cultured Y-1 mouse
      adrenal tumor cells [49-65th passages] could be measured by radioimmunoassay
      after a 0.5 hr incubation. ACTH-stimulated, but not basal, 20-DHP secretion
      increased after 1 mM Ca++ treatment. 5 mM EGTA significantly reduced basal and
      stimulated 20-DHP secretion, although significant ACTH stimulation still
      remained. Basal and stimulated secretion significantly increased when Hb was
      present. Although O2 involvement in the Hb effect was tested by bubbling medium
      with 100% O2 for 10 minutes, basal and stimulated secretion was unaffected. Since
      proteins, such as Hb, non-specifically bind free steroids, enhancing secretion,
      albumin (Al) was compared to Hb. Al enhanced unstimulated, but not ACTH
      stimulated, 20-DHP secretion. The Hb effect may not be due to non-specific
      protein-steroid binding. Ca++ supplementation and chelation studies suggest the
      necessity to optimize co-factors in steroidogenic tissue incubation media to
      maximize basal and stimulated steroid synthesis and secretion. Since
      physiologically relevant Hb levels enhanced basal and stimulated Y-1 cell steroid
      secretion by mechanisms other than protein-steroid binding and soluble O2 had
      little effect, Hb may more efficiently transport O2 to cultured cells than
      soluble O2 diffusion through medium does.

PMID- 7588375
TI  - Sympathoadrenal regulation of adrenocortical steroidogenesis.
AB  - Sympathoadrenal regulation of adrenocortical steroidogenesis was studied on a
      physiological, cellular, molecular and morphological level. The effects of nerve
      activation and of epinephrine (EPI) on adrenal corticosteroid release were
      compared in isolated perfused pig adrenals with preserved nerve supply.
      Splanchnic nerve activation as well as perfusion with EPI provoked a significant
      release of cortisol, aldosterone and androstenedione. In cultured bovine
      adrenocortical cells steroid secretion and accumulation of P450scc, P450(17)
      alpha, P450c21 and P450(11) beta mRNAs were studied after stimulation with EPI
      with or without propranolol or phentolamine. Incubation with EPI stimulated
      steroidogenesis and increased the levels of all four P450-mRNAs. The beta
      adrenergic antagonist propranolol totally blocked the effects of EPI while the
      alpha-antagonist phentolamine had no effect. Using immunohistochemistry, adrenals
      were studied morphologically. The contact zones of the two cell types were
      investigated on an electron microscopical level. Cortical and medullary cells
      were closely interwoven with cortical and chromaffin cells in direct apposition,
      providing the possibility for paracrine interactions. It is concluded that the
      release of corticosteroids can be stimulated through the sympatho-adrenal system.
      The stimulatory action of EPI upon adrenal steroid formation and accumulation of
      all four P450-mRNAs requires beta-adrenergic receptors. Taking into consideration
      the close colocalization of cortical and medullary tissue, this stimulation may
      be mediated by chromaffin cells in a paracrine manner.

PMID- 7588376
TI  - ACTH-receptor deficient mutants of the Y1 mouse adrenocortical tumor cell line.
AB  - Two mutant clones (Y6 and OS3) derived from the ACTH-responsive Y1 mouse
      adrenocortical tumor cell line fail to respond to ACTH with increased adenylyl
      cyclase activity and, as a consequence, are resistant to the steroidogenic
      effects of the hormone. As determined from Northern blot and RNase protection
      assays, ACTH resistance in these mutants results from the failure to accumulate
      ACTH receptor transcripts. The ACTH receptor gene appears to be present in these
      mutants as determined by Southern blot hybridization analysis and can be
      activated following the growth of the mutant cells as tumors in mice, suggesting
      that the ACTH receptor gene is modified in a reversible manner. When mutant cells
      are transformed with a gene encoding the mouse beta 2-adrenergic receptor they
      respond to beta-adrenergic agonists with increased adenylyl cyclase activity in a
      manner that is indistinguishable from a similarly transformed parent Y1 cell
      line. These results suggest that the adenylyl cyclase system in the mutants is
      otherwise intact and that the failure to express ACTH receptor transcripts limits
      the responsiveness of these clones to the hormone.

PMID- 7588377
TI  - Regulation of ACTH receptor mRNA and binding sites by ACTH and angiotensin II in
      cultured human and bovine adrenal fasciculata cells.
AB  - Human (HAC) and bovine (BAC) adrenal fasciculata cells express ACTH and
      angiotensin-II (A-II) receptors. In the present work, we have studied the effects
      of both hormones on ACTH receptor (ACTH-R) mRNA and binding sites. Both HAC and
      BAC expressed several ACTH-R transcripts. Although in both cell types, ACTH and A
      II increased ACTH-R transcripts in a time- and dose-dependent manner, the maximal
      effects were different. Thus, ACTH at 10(-9) M enhanced 21- and 5-fold the level
      of ACTH-R mRNA and binding sites in HAC, whereas in BAC both parameters were
      enhanced only 3-fold. A-II at 10(-7) M increased 17- and 3.5-fold ACTH-R mRNA and
      binding sites in HAC, whereas in BAC, it caused only a 2-fold increase in ACTH-R
      mRNA and a small decrease in receptor number. In HAC, the stimulatory effects of
      both hormones on ACTH-R mRNA are mainly transcriptional, whereas in BAC they are
      mainly post-transcriptional, by decreasing the rate of degradation of ACTH-R
      mRNA. The stimulatory effects of ACTH on ACTH-R in both HAC and BAC were
      associated with an enhanced steroidogenic response to further hormonal
      stimulation. In contrast, specific species differences were observed with A-II.
      Thus, in HAC A-II increased ACTH-R mRNA and binding sites and the ACTH-induced
      cortisol production, whereas in BAC, A-II caused a slight decrease of ACTH
      binding sites and steroidogenic desensitization.

PMID- 7588378
TI  - Hormonal regulation of angiotensin II type 1 receptor expression and AT1-R mRNA
      levels in human adrenocortical cells.
AB  - Human adrenocortical H295R cells express AII receptors which are predominantly of
      the AT1 but not AT2 subclass. These receptors are functionally coupled to
      phosphoinositidase C in a manner similar to that seen in fetal human, sheep and
      bovine adrenocortical cells. Treatment of H295R cells with forskolin or dbcAMP to
      activate the protein kinase A pathway caused a rapid (maximal by 3 h) and
      sustained decrease in AT1-R mRNA levels which in turn preceded a time-dependent
      (maximal by 12 h) and dose-dependent loss of [125I]AII binding and
      phosphoinositidase C activation on subsequent AII challenge. Thus, both decreased
      AT1-R mRNA levels and functional receptor expression appear to parallel each
      other in response to activation of protein kinase A. Activation of the
      Ca2+/protein kinase C pathways by treatment with AII also caused a rapid (maximal
      by 3 h) and dose-dependent loss in AT1-R mRNA, but mRNA levels subsequently rose
      again, approaching control levels by 36 h. Treatment with AII for 48 h had little
      effect on either [125I]AII binding or the subsequent phosphoinositidase C
      response. The effect of AII, but not forskolin, was blocked by the presence of
      cycloheximide. The action of AII on AT1-R mRNA was probably mediated through both
      protein kinase C and Ca(2+)-sensitive protein kinases as the effect at 4 h was
      not completely reproduced by phorbol ester alone, but was fully reproduced by a
      combination of phorbol ester and Ca2+ ionophore. However, increased Ca2+ influx
      alone, due to treatment with BAYK8644 or elevated extracellular K+, also resulted
      in a decrease in AT1-R mRNA levels. Thus in the H295R cell, control of AT1-R
      expression appears to be complex, being achieved at least in part through control
      of the level of AT1-R mRNA by multiple independent signaling pathways including
      protein kinase A, protein kinase C and Ca2+.

PMID- 7588379
TI  - Stimulation of cortisol production through angiotensin AT2 receptors in bovine
      fasciculata cells.
AB  - Bovine fasciculata cells in culture (BAC) express both AT1 and AT2 angiotensin
      receptors. The role and signaling pathways of this latter receptor are still the
      subject of debate. We found that in BAC stimulation of cortisol (F) production by
      angiotensin II (A II) is accounted for by both receptor subtypes. We have
      investigated the potential AT2 signalling pathways involved in this response. As
      previously described in other cells, we found this receptor to mediate inhibition
      of ANP stimulated cGMP production through a phosphodiesterase independent
      pathway. This phenomenon does however not appear to be involved in cortisol
      production as this response was not affected by the addition of 8-Br-cGMP or ANP.
      It was however abolished after down-regulation of PKC by phorbol esters, but not
      by Gi inhibition with pertussis toxin. Moreover and as opposed to the AT1
      mediated response, AT2 receptor stimulation potentiated K+ induced F production.
      In conclusion, these observations suggest that the AT2 pathway which mediates F
      production requires intact PKC and might involve a Gi independent stimulation of
      Ca++ or K+ channels.

PMID- 7588381
TI  - Increased aldosterone-18-glucuronide/tetrahydroaldosterone ratios in pregnancy.
AB  - In the present study the aldosterone-18-glucuronide and tetrahydroaldosterone
      values in 24 hour urine collections of healthy nonpregnant women, women with
      normal pregnancies and women with pregnancy induced hypertension (PIH) were
      compared. In pregnancy an elevated excretion of both aldosterone metabolites was
      found. The Q-ratio (aldosterone-18-glucuronide/tetrahydro-aldosterone+aldosterone
      18-glu cur onide) was also increased compared to healthy nonpregnant women. The
      elevated Q-ratios point out to increased formation of aldosterone-18-glucuronide.
      This predominantly renal metabolite may reflect greater availability of
      aldosterone molecules for interaction with mineralocorticoid receptor in the
      kidney.

PMID- 7588380
TI  - Expression of type 1 angiotensin II receptors in human aldosteronomas.
AB  - Type 1 angiotensin II (AII) receptors (AT1 receptors), besides stimulation of
      aldosterone secretion, seem to transduce the growth factor-like activity of AII
      on glomerulosa cells. Although a local renin-angiotensin system and AII synthesis
      have been found in human adrenals and aldosteronomas, it is unclear whether
      aldosteronomas express AT1 receptors. Utilizing polymerase chain reaction (PCR)
      and reverse transcription-PCR (RT-PCR) with primers complementary to both genomic
      and cDNA sequences of human AT1 receptor, we have amplified and cloned a 734 bp
      fragment of the AT1 coding region. This DNA, after cloning and sequencing, was
      used for Northern analysis. Total RNA was extracted from 5 non-tumorous adrenals
      and 5 aldosteronomas. AT1 mRNA (approximately 2.4 kb) was expressed in all the
      aldosteronomas tested. Densitometric analysis of AT1 signals, corrected by beta
      actin expression, when compared to non-tumorous adrenals, did not show
      significant differences. AT1 receptor density and affinity in cell membrane
      obtained from 9 non-tumorous adrenal cortex and 8 aldosteronomas were also
      studied. 125I-AII was used as ligand and Dup 753 as AT1 antagonist: AT1 receptor
      density and affinity were not significantly different in aldosteronomas vs non
      tumorous adrenal cortex. In conclusion, the expression of AT1 gene and the
      formation of an apparently normal receptor suggest that AT1 receptor should have
      a role in aldosteronoma cell biology.

PMID- 7588382
TI  - Study on the mechanisms of glucocorticoid-induced hypertension: glucocorticoids
      increase transmembrane Ca2+ influx in vascular smooth muscle in vivo.
AB  - Blood pressure (BP) and ex vivo influx rate of Ca2+ in excised aortae were
      measured in rabbits implanted with silastic rubber strips impregnated with
      glucocorticoids (GC) [dexamethasone (DEX) or cortisol (FK)], or carbenoxolone
      (CX) [inhibitor of 11 beta-hydroxysteroid dehydrogenase (11-HSD), in a large (lg)
      or a small (sm) (10 times smaller) concentration], or FK plus CX (sm), or DEX
      plus RU 38486 (a specific GC-receptor blocker). After 4-6 weeks rabbits implanted
      with DEX, CX (lg), and FK+CK (sm) developed hypertension. Those implanted with FK
      alone (yielding physiological serum concentration of FK), CX (sm), and DEX+RU
      38486 did not develop hypertension. Rates of unidirectional influx of Ca2+
      measured in rings of excised aortae were in all hypertensive rabbits more than
      twice those in the control rabbits (implanted with silastic strips not containing
      any steroids). In all normotensive rabbits, Ca2+ influx rates remained normal. We
      conclude that, in analogy with the in vitro findings in cultured vascular smooth
      muscle (VSM) cells treated with GC, also in vivo, the elevation of tissue levels
      of GC causes an increase in the influx rate of Ca2+ in VSM. We propose that this
      may be the main pathogenic mechanism of GC-induced hypertension.

PMID- 7588383
TI  - Internalisation of the type I angiotensin II receptor (AT1) and angiotensin II
      function in the rat adrenal zona glomerulosa cell.
AB  - Using a specific monoclonal antibody (6313/G2) to the first extracellular domain
      of the type 1 receptor (AT1), we showed that most of the receptor is internalised
      in the rat glomerulosa cell. When viable glomerulosa cells are incubated with
      6313/G2, the receptor is transiently concentrated on the cell surface, and
      aldosterone output is stimulated. This stimulated output is enhanced by neither
      threshold nor maximal stimulatory concentrations of AII amide, although the
      antibody does not inhibit AII binding to the receptor. The antibody directly
      stimulates inositol trisphosphate (IP3) generation, but, while having no
      intrinsic action on protein kinase C (PKC) activation, it significantly inhibits
      the PKC response to angiotensin II. The data suggest that although the receptor
      is mostly internalized, recycling to the plasma membrane is constitutive, or
      regulated by unknown factors. Retention of the AT1 receptor in the membrane is
      alone enough to allow sufficient G protein interaction to generate maximal
      steroidogenic effects, through IP3 generation. PKC activation induced by
      angiotensin II has no bearing on steroidogenesis in the dispersed glomerulosa
      cell system.

PMID- 7588384
TI  - Characterization of gap junction expression in the adrenal gland.
AB  - To characterize the presence of gap junctions in adrenal tissue we used
      immunohistochemical analysis of connexin expression in whole adrenal glands and
      in primary rat adrenal cortical cell cultures. alpha 1 (connexin 43) gap junction
      protein was demonstrated in rat adrenal glands and in primary adrenal cell
      cultures. The alpha 1 gap junction proteins were present in different amounts
      such that little or no alpha 1 antigen was detected in the zona glomerulosa (ZG),
      while cells of the zona fasciculata (ZF) and zona reticularis (ZR) stained
      intensely. There was an inverse relationship between cell division rate and gap
      junction number in the intact adrenal gland. We placed the cells from the most
      intensely staining areas (ZF/ZR) of the rat adrenal cortex into culture. These
      primary adrenal cells expressed alpha 1 gap junction antigen on their cell
      surfaces in regions of cell-cell contact. ACTH (40mU/ml) treatment resulted in an
      increase in gap junction expression relative to controls in primary rat adrenal
      cultures. These results indicate that the abundance of gap junction expression is
      differential in the cortical zones and can be modulated by hormonal stimulation.
      These observations are also thought to reflect morphological and functional
      differences in adrenal cortical zones.

PMID- 7588386
TI  - Expression of the steroidogenic acute regulatory (StAR) protein: a novel LH
      induced mitochondrial protein required for the acute regulation of
      steroidogenesis in mouse Leydig tumor cells.
AB  - The acute response of steroidogenic cells to hormone stimulation is the
      mobilization of cholesterol from cellular stores and the outer mitochondrial
      membrane to the inner mitochondrial membrane and the cholesterol side-chain
      cleavage complex (CSCC) where the first enzymatic reaction occurs. It has been
      well established that the translocation of cholesterol from the outer to the
      inner mitochondrial membrane requires de novo protein synthesis and that this
      process is the rate-limiting, regulated step in steroidogenesis. We have purified
      a novel mitochondrial protein (named StAR) from the MA-10 mouse Leydig tumor
      cells which we have previously proposed represents a strong candidate for the
      newly synthesized regulatory protein in steroidogenesis. The cDNA for StAR was
      cloned and we have demonstrated that expression of the StAR protein in MA-10
      cells in the absence of hormone stimulation results in a 3 fold increase in
      progesterone production compared to mock transfected cells. These studies
      indicate a direct indicate a direct relationship between StAR expression and
      steroidogenesis, therefore, we conclude that StAR is required in the acute
      regulation of steroidogenesis.

PMID- 7588385
TI  - Routes and regulation of NADPH production in steroidogenic mitochondria.
AB  - The first and rate-limiting step of steroidogenesis is catalyzed by the
      mitochondrial cholesterol side chain cleavage system that is dependent on NADPH.
      The pathways of NADPH generation in steroidogenic mitochondria include three
      major routes catalyzed by: 1. NADP-linked malic enzyme, 2. NADP-linked isocitrate
      dehydrogenase, and 3. nicotinamide nucleotide transhydrogenase. The main route
      may differ among cell types and across species. Generally operation of
      alternative routes, with different substrates is not excluded. The oxidation of
      NADPH by the mitochondrial P450 systems is not tightly coupled with substrate
      metabolism, as these systems can reduce O2 by a single electron to produce
      harmful superoxide radical. To minimize such futile NADPH oxidation, NADPH
      generation may be regulated by two types of mechanisms: 1. Feedback mechanisms
      that maintain the ratio of NADPH/NADP+ at a steady-state level by enhancing the
      rate of NADPH production to keep up with its rate of oxidation, e.g., allosteric
      regulation of enzymes involved in NADPH production. 2. Hormonal signals that
      enhance the level of NADPH production in coordination with steroidogenesis. One
      major hypothesis with experimental evidence is that stimulation of mitochondrial
      NAD(P)H synthesis is mediated by Ca++ as a second messenger of tropic factors.
      Tropic stimulation of cells increases the levels of Ca++ in the cytosol and then
      in the mitochondrial matrix, and the rise in Ca++ activates enzymes involved in
      NAD(P)H synthesis. These regulatory mechanisms most probably operate in concert
      adjusted to the steroidogenic activity of the cell.

PMID- 7588387
TI  - Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland.
AB  - The aim of these studies was to determine the intraadrenal mechanism of
      interleukin-1 (IL-1)-induced corticosterone release from the rat adrenal gland.
      To accomplish this, the role of catecholamines and eicosanoids on IL-1-induced
      corticosterone release was determined. Experiments were conducted on primary
      cultures of dispersed rat adrenal cells. Dose-dependent increases (P < 0.05) in
      corticosterone concentration were observed when primary adrenal cells were
      incubated with different doses (10(-10) to 10(-8) M) of IL-1 alpha. IL-1 alpha
      and IL-1 beta elevated corticosterone release after a 24 hr incubation period.
      ACTH elevated corticosterone levels at 4 and 24 hr. The stimulatory effect of IL
      1 on corticosterone release was mimicked by epinephrine (1 microM), and was
      selectively blocked by the alpha-adrenergic antagonist, phentolamine (10 microM).
      The beta-adrenergic antagonist, propranolol (10 microM), did not change IL-1
      induced corticosterone release. Neither phentolamine nor propranolol had an
      effect on ACTH stimulated corticosterone release. Both IL-1 alpha and IL-1 beta
      significantly elevated (P < 0.05) epinephrine levels after a 24 hr incubation
      period compared to media-treated controls. Untreated adrenal cells fixed for
      immunohistochemical staining with a specific anti-rat tyrosine hydroxylase
      antibody indicate that the primary adrenal cell preparation contained 3.1 +/-
      0.45% tyrosine hydroxylase positive cells. On the ultrastructural level, the
      chromaffin cells were found to be in direct cellular contact with cortical cells.
      Although IL-1 alpha significantly increased (P < 0.05) prostaglandin E2 (PGE2)
      levels from primary adrenal cells, the presence of the cyclooxygenase inhibitor,
      indomethacin (10 microM) significantly inhibited IL-1 alpha-induced PGE2
      secretion without altering the effect of IL-1 alpha on corticosterone release.
      Inhibitors of the lipoxygenase system (5-lipoxygenase, 10 microM) and the
      lipoxygenase and cytochrome P450 monooxygenase systems (nordihydroguaiaretic
      acid, 10 microM) did not effect IL-1 alpha-induced corticosterone or PGE2
      release. These observations indicate that IL-1 stimulates the local release of
      catecholamines, which, in turn, stimulates corticosterone release through an
      alpha-adrenergic receptor; this mechanism is independent of PGE2.

PMID- 7588389
TI  - In vivo effects of adrenocorticotropin on c-jun, jun-B, c-fos and fos-B in rat
      adrenal.
AB  - We have studied the in vivo effects of adrenocorticotropin (ACTH) on mRNA levels
      of c-jun, jun-B, c-fos and fos-B, in rat adrenals. In control rats, c-jun mRNA
      was abundant in both zona glomerulosa (ZG) and zona fasciculatareticularis (ZF
      R). Although less abundant than c-jun, the mRNA of jun-B could be detected in
      both zones, whereas that of c-fos could barely be detected and that of fos-B
      could not. After an injection with short acting ACTH, mRNA levels of c-jun, c
      fos, jun-B and fos-B were maximally increased in both zones within 30 min. Within
      5h, the mRNA levels decreased towards control levels for c-jun, to below control
      levels for jun-B, and to undetectable levels for c-fos and fos-B. After a
      sustained stimulation by two daily administrations of long acting ACTH, the mRNA
      of c-jun was still abundant in both zones, although its level decreased by 50%
      and 80% after 36h and 9 days, respectively, after the first injection. Under such
      conditions, the mRNA level of jun-B was increased, that of fos-B could barely be
      detected, and that of c-fos could not be detected. To conclude, these results
      suggest that jun-B, fos-B, and also c-fos play a role in triggering early events
      leading to an increased steroidogenesis, as well as a basic role in maintaining
      the integrity of the adrenal cortex in the case of c-jun and jun-B.

PMID- 7588388
TI  - The effects of KN62, a Ca2+/calmodulin-dependent protein kinase II inhibitor, on
      adrenocortical cell aldosterone production.
AB  - The effects of KN62 on aldosterone secretion have been studied using an
      angiotensin II (AII)- and K(+)-responsive human adrenocortical tumor cell line
      (H295R). Basal aldosterone secretion (measured by RIA) was 0.57 +/- 0.22 pmol/mg
      protein.h. The physiologicial agonists AII (10 nM) and K+ (14 mM) increased
      aldosterone secretion by 6.9- and 5.0-fold, respectively. Aldosterone secretion
      was also stimulated by dibutyryl cyclic AMP (dbcAMP, 1 mM, 10.3-fold over basal).
      Nifedipine dose-dependently inhibited K(+)- and AII-stimulated aldosterone
      secretion. In contrast, dbcAMP-stimulated secretion was relatively insensitive to
      this agent (26.8% inhibition at 1 microM nifedipine). K(+)- and AII-stimulated
      aldosterone production was also dose-dependently inhibited by KN62, which
      produced 93.9% and 82.3% inhibition at 10 microM KN62 (both p < 0.01). In order
      to test the specificity of KN62 in H295R cells, its effects on various other
      steroidogenic agonists were assessed. KN62 dose-dependently inhibited aldosterone
      secretion stimulated by dbcAMP, 22-hydroxycholesterol and pregnenolone. In
      addition, KNO4, a derivative of KN62 which is not a potent inhibitor of CaM
      Kinase II, exhibited a similar pattern of inhibition. These data confirm the
      requirement for extracellular Ca2+ in the stimulation of human adrenocortical
      cell aldosterone secretion by AII and K+. However, the non-specific inhibitory
      effects of KN62 in H295R cells limit the usefulness of this agent as a tool for
      investigations of the involvement of CaM kinase II in adrenocortical
      steroidogenesis.

PMID- 7588390
TI  - P450aldo in hamster adrenal cortex: immunofluorescent and immuno-gold electron
      microscopic studies.
AB  - The zonal distribution of aldosterone synthase cytochrome P450 (P450aldo) in the
      adrenal cortex of male hamsters was investigated by immunofluorescence and
      electron microscopy, using an anti-P450aldo peptide antibody. On cryostat
      sections the immunolocalization of P450aldo was confined to the zona glomerulosa
      cells. On semi-thin plastic sections, P450aldo was shown to be located in
      mitochondria. Studies in electron microscopy, using the colloidal gold technique,
      confirmed that P450aldo was located in mitochondria.

PMID- 7588391
TI  - ACTH-dependent proteolytic activity of a novel phosphoprotein (p43) intermediary
      in the activation of phospholipase A2 and steroidogenesis.
AB  - Arachidonic acid (AA) and the lipooxygenase products have been shown to play an
      obligatory role in the mechanism of action of LH and ACTH, at a point after cAMP
      dependent phosphorylation. We have demonstrated the presence of a phosphoprotein
      (p43) that responds to cAMP signals to induce steroid synthesis in adrenocortical
      tissue, an effect that is blocked by phospholipase A2 inhibitors. In this report
      we demonstrate that p43 exhibits autoproteolytic activity that is regulated by
      ACTH. Protein purified from ACTH-treated animals exhibited degradation in some of
      the isoforms resolved on two dimensional gel electrophoresis. Proteinase
      inhibitors (PMSF and 1,10 phenantroline) inhibited steroid synthesis induced by
      ACTH and 8-Br-cAMP in intact cells. Addition of exogenous AA reverted in part
      that inhibition. Here we present evidence for a hormone-regulated proteolytic
      activity of p43 and for the inhibition of steroidogenesis by proteinase
      inhibitors acting prior to the release of arachidonic acid.

PMID- 7588392
TI  - Expression of human P450c17 as an export protein in Saccharomyces cerevisiae.
AB  - Cytochrome P450c17 (P450c17), together with cytochrome P450c21 (P450c21), plays
      an important role in progesterone metabolism in the mammalian adrenal cortex. Low
      levels of expression and the presence of other steroidogenic enzymes in adrenal
      cortex endoplasmic reticulum (ER) impedes purification and characterisation of
      wild type as well as mutant forms of the hemoprotein. Heterologous gene
      expression systems have previously been used successfully to express active
      P450c17. Heterologous expression can also be used for the preparation of anti
      P450c17-IgG. For antibody production larger amounts of pure P450c17 peptide,
      rather than the active protein, is, however, desirable. If the expressed protein
      can be affinity tagged and secreted into the medium, isolation and purification
      will be facilitated. Saccharomyces cerevisiae, YPH259, was transformed with a
      modified YCplac111 yeast expression-secretion vector (pPRL2). The gene coding for
      a truncated human P450c17 (signal anchor sequence 1-18 was removed) was inserted,
      in reading frame, downstream from the leader sequence MF alpha. A histidine tag
      was incorporated at the C-terminus. The modified yeast expression vector was
      expressed in yeast, the secreted P450c17-peptide purified by affinity
      chromatography and identified by immunoblot analysis.

PMID- 7588394
TI  - Structure-function studies on mutants of adrenal ferredoxin.
AB  - Mutants of the adrenal ferredoxin (adrenodoxin) have been expressed in E. coli in
      order to improve the understanding of its structure and function. Replacement of
      the ligands to the /2Fe-2S/ center, C46, C52, C55 and C92, by serine, histidine
      or aspartic acid lead to apoproteins not incorporating the iron-sulfur cluster,
      whereas C95S forms a functionally active holoprotein. C-terminal deletions up to
      amino acid 109 affect the conformation around the iron-sulfur cluster in
      adrenodoxin and the interaction with CYP11A1 and CYP11B1, but not with
      adrenodoxin reductase. The presence of P108 is necessary for incorporation of the
      /2Fe-2S/ cluster and obviously for correct folding of adrenodoxin.

PMID- 7588393
TI  - The effect of cytochrome b5 on progesterone metabolism in the ovine adrenal.
AB  - The production of glucocorticoids and mineralocorticoids in the endoplasmic
      reticulum (ER) of the mammalian adrenal cortex are, to a great extent, regulated
      by the relative activities of the steroid 21-hydroxylase (P450c21) and steroid 17
      alpha-hydroxylase (P450c17) enzymes. Progesterone can be 17 alpha-hydroxylated to
      yield 17 alpha-hydroxyprogesterone which, under certain conditions and in certain
      species, can be further lyased to adrostenedione by the same enzyme. P450c21 can
      21-hydroxylate 17 alpha-hydroxyprogesterone to yield cortisol but also converts
      progesterone to corticosterone. Cytochrome b5 (cyt b5) can also participate in
      the regulation of adrenal microsomal steroid hydroxylase activities by changing
      the rates of the P450c21 and P450c17 reactions or by affecting the 17 alpha
      hydroxylation:17,20-lyase ratio of progesterone, by P450c17. We investigated the
      metabolism of progesterone by sheep adrenal microsomes to identify the products
      of the different steroid hydroxylase activities in the ER and to investigate the
      influence of cyt b5 on progesterone metabolism using purified ovine cyt b5 and
      anti-cyt b5. The P450c17-activity in sheep adrenal microsomes is inhibited by the
      addition of purified cyt b5 while anti-cyt b5 IgG stimulates the 17 alpha
      hydroxylation of progesterone. No 17,21-lyase-activity towards progesterone could
      be detected in sheep adrenal microsomes.

PMID- 7588395
TI  - Intraadrenal steroid metabolism in the guinea pig: guinea pig adrenal microsomes
      metabolize androstenedione in a manner distinct from liver microsomes.
AB  - Several immunochemical homologs of hepatic cytochromes P450 (CYPs) capable of
      steroid catabolism have been identified in the guinea pig adrenal cortex. Their
      predominance in males suggests a role in sex-differentiated metabolism of
      androgens. Therefore, we examined the ability of microsomes from male guinea pig
      adrenals and liver to metabolize androstenedione. Microsomes were incubated in
      the presence of radiolabeled steroids, the products of the reaction extracted,
      separated by TLC, and visualized by autoradiography. Metabolites were identified
      by comigration with commercially available standards in several solvent systems,
      in one and two dimensional TLC. Microsomes from both tissues metabolized
      androstenedione. However, the products formed differed markedly in the two
      tissues. Liver microsomes formed one major metabolite, testosterone. It
      represented 85% of the metabolized androstenedione. 6 beta-Hydroxylated
      androstenedione and testosterone each comprised 3-4% of the liver metabolites. In
      addition, at least 10 other products were formed, but taken together they
      constituted less than 8% of the metabolized androdostenedione. Adrenal
      microsomes, on the other hand, produced several major metabolites: 16 alpha-, 16
      beta-, and 6 beta-hydroxy-androstenedione, plus one unidentified product
      constituted 93% of the metabolized androstenedione. 16 alpha-Hydroxylation of
      androstenedione was 60 fold, 16 beta-hydroxylation 12 fold, and 6 beta
      hydroxylation 2.5 fold greater in adrenal than in liver microsomes. The
      unidentified product, which was the least polar, was formed exclusively by
      adrenal microsomes. The hydroxylation reactions performed by adrenal tissue are
      consistent with the presence in adrenal microsomes of immunochemical homologues
      of members of the CYP1A, 2B, 2C and 3A families which have known steroid
      hydroxylation functions in liver. The Kms of the formation of 16 alpha-, 16 beta-
      and 6 beta-hydroxyandrostenedione by adrenal microsomes are in the range reported
      for steroid hydroxylation reactions in rat liver tissue. Their distinct values
      suggest that these hydroxylation steps are performed by different CYPs. However,
      assignment of site-specific steroid hydroxylation reactions to individual hepatic
      CYP homologs in the adrenal requires further investigation and is being pursued
      using combined techniques of biochemistry and molecular biology.

PMID- 7588396
TI  - Regulation of 21-hydroxylase activity by steroids.
AB  - In this study, we investigated the effect of steroids on guinea pig and bovine
      adrenal steroidogenesis, especially 21-hydroxylase activity. Analysis of guinea
      pig adrenal steroids indicated the presence of high concentrations of
      androstenedione in the guinea pig adrenal; furthermore, in vitro studies using
      guinea pig adrenal cortex cells in primary culture confirmed that androstenedione
      is one of the major C19 steroids produced and secreted. The direct action of
      steroids on steroid production by adrenal cells was investigated. Our data
      indicate that steroids themselves increase C19 steroid synthesis and inhibit
      glucocorticoid production by guinea pig adrenal cells without affecting gene
      expression for steroidogenic enzymes. Incubation of a series of C19 steroids,
      namely, androstenedione, with guinea pig adrenal cell cultures demonstrated that
      the decrease in 21-hydroxylase activity is largely independent of the androgenic
      activity of C19 steroids. RU38486, a synthetic C18 steroid possessing a 4-ene-3
      ketosteroid with an aryl group at position 11 and a very low affinity for the
      androgen receptor, also irreversibly altered 21-hydroxylase activity. An effect
      of RU38486 on 21-hydroxylase activity was also demonstrated in bovine adrenal
      cells. Further studies with bovine adrenal cells showed that the decrease in 21
      hydroxylase activity induced by RU38486 was accompanied by a small but
      significant inhibition of P450c21 protein levels at both basal and ACTH
      stimulated levels. In summary, our data indicate that alteration of 21
      hydroxylase activity by steroids is likely due to a direct action on P540c21
      protein, and the levels of androstenedione in the adrenal are high enough to
      inhibit 21-hydroxylase activity.

PMID- 7588401
TI  - Clinical investigation of 11 beta-hydroxysteroid dehydrogenase.
AB  - At least two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) have
      been identified, and clinical studies have illustrated their physiological and
      pathological significance. In the kidney, a high affinity 11 beta-OHSD2
      inactivates cortisol to cortisone and protects mineralocorticoid receptors from
      cortisol. In the liver, a low affinity 11 beta-OHSD1 converts cortisone to
      cortisol, and may ensure that glucocorticoid receptors are adequately exposed to
      cortisol. In vascular smooth muscle, the conversion of cortisol to cortisone
      influences vascular tone. Defects in 11 beta-OHSD2 probably account for
      mineralocorticoid excess in the syndromes of Apparent Mineralocorticoid Excess,
      licorice administration, and ectopic ACTH syndrome. Defects in 11 beta-OHSD1 may
      be important in essential hypertension, and polycystic ovarian syndrome. The
      underlying mechanism for all of these defects, and the putative role of
      endogenous inhibitors of 11 beta-OHSD, remains unclear. In future, the
      measurement of the activity of individual isoforms should resolve this
      uncertainty.

PMID- 7588398
TI  - Adrenal-specific transgene expression and derivation of conditionally immortal
      rat adrenocortical cell lines.
AB  - Conditional immortalisation of cells is a powerful tool for establishing in vitro
      models maintaining a differentiated phenotype. We are utilising this approach to
      derive cell lines that maintain the characteristics of glomerulosa and
      fasciculata cells of the adrenal cortex. Such cell lines should provide a system
      in which to study aspects of adrenocortical function that are relevant to
      hypertension, such as the effects of the renin-angiotensin system on
      steroidogenesis.

PMID- 7588397
TI  - Structure and expression of the CYP21 (P450c21, steroid 21-hydroxylase) gene with
      respect to its deficiency.
AB  - Steroid 21-hydroxylase (P450c21) deficiency is the major cause of a common
      genetic disease, congenital adrenal hyperplasia, with the symptoms of
      virilization due to steroid imbalance. We have devised a fast diagnostic method
      to detect common mutations in the c21B gene by a two-step gene amplification
      procedure coupled to restriction digestion. This procedure does not require
      isotopes and is suitable for routine use in a hospital setting. In addition, we
      have developed a procedure for the production of active P450c21 in E. coli. We
      tested many different vector and bacterial strain combinations to find out the
      best condition for P450c21 expression. The bacteria harboring the P450c21
      expression plasmid were grown in a rich media supplemented with trace metals,
      heme biosynthesis precursor delta-levulinic acid, and induced with IPTG at 20
      degrees C for 48 h. We found that low growth temperature and long induction time
      were important for abundant synthesis of P450c21 in E. coli.

PMID- 7588400
TI  - Ovine 11 beta-hydroxysteroid dehydrogenase: from gene to function.
AB  - Two distinct isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) with
      respect to enzymatic activity were identified in the ovine liver and kidney. 11
      beta-HSD1 (the hepatic isoform) was reversible and NADP(H)-dependent. By
      contrast, 11 beta-HSD2 (the renal isoform) was unidirectional and NAD-dependent.
      Ovine placenta contained both forms of 11 beta-HSD activities. The cDNA encoding
      ovine 11 beta-HSD1 was cloned, and used as a probe to study 11 beta-HSD1 gene
      expression in fetal sheep during development. It was found that fetal and adult
      liver was the major site of 11 beta-HSD1 biosynthesis, and that 11 beta-HSD1 gene
      expression was regulated in a tissue-specific and developmentally programmed
      manner. Two non-functional variants of 11 beta-HSD1 were also identified. In
      addition, sheep kidney was unique in that both 11 beta-HSD1 mRNA and activity
      were absent. Although the physiological significance of 11 beta-HSD in individual
      fetal organs during development remains largely speculative, 11 beta-HSD in the
      fetal pituitary may contribute, at least in part, to the proposed resetting of
      cortisol negative feedback on pituitary ACTH during the last few days of
      gestation. In the fetal liver, the action of 11 beta-HSD may lead to the
      formation of cortisol which could act locally as well as systematically to
      modulate developmental processes. Placental 11 beta-HSD may protect fetus from
      exposure to the growth-inhibiting effects of maternal glucocorticoids.

PMID- 7588399
TI  - Divergence between genotype and phenotype in relatives of patients with the
      intron 2 mutation of steroid-21-hydroxylase.
AB  - We studied 95 patients and their relatives with the classical salt wasting (SW)
      and simple virilizing (SV) form of CAH. SSCP/heteroduplex analysis allowed fast
      and efficient screening for the most common 21-hydroxylase mutations (e.g.
      deletions, splice site mutation in intron 2 (bp 656), Ile172Asn mutation in exon
      4) and determination of the relative intensities of CYP21A and CYP21B genes. The
      splice site mutation in intron 2 was found as the most frequent cause of 21
      hydroxylase deficiency (35% of our patients). There is a strong genetic
      association between the mutation in intron 2 and the SW form of CAH. On the other
      hand, about 20% of our patients with the intron 2 mutation have the SV phenotype.
      Interestingly, homozygous splice site mutations in intron 2 were also detected in
      some parents or other relatives with no phenotypic changes typical for CAH
      (clinical evaluation, steroid hormone levels). In those patients with SV-CAH and
      especially in the relatives with the homozygous intron 2 mutation and an
      unaffected phenotype, the splice site mutation could be "leaky". mRNA-splicing in
      the adrenal cortex should result in a high degree of normal mRNA species. This is
      in contrast to in vitro expression studies of CYP21B genes containing the intron
      2 mutation, performed by other groups. However, the results of in vitro
      expression studies are not always reflecting the in vivo conditions in the
      adrenal cortex. This situation is in good agreement with the variable degree of
      normal spliced mRNA and different phenotypic severity in intron mutations found
      in thalassemia.

PMID- 7588402
TI  - Cloning of cDNA encoding an NAD(+)-dependent isoform of 11 beta-hydroxysteroid
      dehydrogenase in sheep kidney.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of
      cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This
      activity may be required to confer normal ligand specificity upon the
      mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated
      from rat liver, a different isozyme is apparently expressed in mineralocorticoid
      target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by
      expression screening using Xenopus oocytes. The cDNA is 1.8 kb in length and
      encodes a protein of 427 amino acid residues with a predicted M(r) of 46,700.
      When expressed in oocytes, this enzyme functions as an NAD(+)-dependent 11 beta
      hydrogenase with very high affinity for steroids, but it has no detectable
      reductase activity. It is 37% identical in amino acid sequence to an NAD(+)
      dependent isozyme of 17 beta-hydroxysteroid dehydrogenase, but only 20% identical
      to the NADP(+)-dependent liver isozyme of 11-HSD. It is expressed at high levels
      in the kidney and adrenal and at lower levels in the colon. The corresponding
      gene is present in a single copy in the sheep genome. In humans, this gene is a
      candidate locus for the syndrome of apparent mineralocorticoid excess, a form of
      hypertension postulated to result from 11-HSD deficiency in mineralocorticoid
      target tissues.

PMID- 7588403
TI  - Neuropeptides in the adrenal gland: distribution, localization of receptors, and
      effects on steroid hormone synthesis.
AB  - In this review we defined and classified the neuropeptides (NPs) related to the
      adrenal gland, according to Palkovits (Frontiers Neuroendocrinol 10:1 1988). The
      concentration (RIA) and distribution (immunohistochemistry) of NPs, as well as
      the localization of the receptors (radioligand studies) were summarized. Direct
      effects of NPs on aldosterone and corticosterone synthesis obtained by in vivo,
      in situ perfusion, and in vitro experimental approaches were reviewed. Data (from
      different rat strains and genders) for 35 NPs are presented.

PMID- 7588405
TI  - Localization of P450aldo and P45011 beta in normal and regenerating rat adrenal
      cortex.
AB  - A novel layer of cells that do not contain both P450aldo and P45011 beta has been
      discovered between the zonae glomerulosa and fasciculata of the rat adrenal
      cortex. Since P450aldo and P45011 beta are the enzymes responsible for the
      formation of aldosterone and corticosterone, respectively, the cells in that zone
      are presumably inert in synthesizing both aldosterone and corticosterone, in
      other words, the layer is composed of cells that have no zone-specific endocrine
      function as an adrenocortical component. Cytologically, the layer consists of
      tightly packed cells, which contain a lesser amount of lipid droplet than the
      cells in the other zones, and appears as a white ring or a white zone in the
      double immunostaining with anti P450aldo and anti P45011 beta. Upon angiotensin
      II-stimulation evoked by Na-deficiency, the number of the zona glomerulosa cells
      expressing P450aldo increases for the initial 2 or 3 days and then the P450aldo
      containing zona glomerulosa cells begin to proliferate. Thus angiotensin II
      serves as a proliferator of the zona glomerulosa cells of the rat adrenal cortex.
      During the period, the thickness of the white zone decreases for initial 3 days
      and becomes constant after 5 or 6 days, being about 5% of the total cell number
      of the adrenal cortex. When localization of replicating cells was examined in the
      adrenal cortex, they were found to be concentrated in and around the white zone.
      Then the pulse-chase experiments with BrdU showed that the labeled cells migrated
      out of the white zone and into the zonae fasciculata and reticularis. The
      localization of the replicating cells in the regenerating adrenal cortex was also
      around the region between the zonae glomerulosa and fasciculata. On the basis of
      these findings, we suggest that the newly discovered cell layer (the white zone)
      is the stem cell zone of the rat adrenal cortex.

PMID- 7588406
TI  - Human adrenal CYP11B1: localization by in situ-hybridization and functional
      expression in cell cultures.
AB  - CYP11B1 was detected in the human adrenal cortex and in human adenomas by in situ
      hybridization methods. Specific riboprobes were generated and hybridized to
      sections of an Aldosterone Producing Adenoma (APA), the non-tumour portion of the
      corresponding adrenal gland and two adenomas not related to hyperaldosteronism.
      P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis. Semi
      quantitative analysis has been performed and seems to be applicable for a further
      classification of adrenal tumours. Stable expression of CYP11B1 cDNA was
      performed in V79 cells. The interference of different substances (metyrapone,
      spironolactone and different imidazole derivatives) with CYP11B1 activity was
      studied using this cell line. The cell line revealed to be suitable for analysis
      of the active site of CYP11B1 as well as for analysis of side effects of drugs on
      steroidogenesis.

PMID- 7588407
TI  - Haplotype analysis of CYP11B2.
AB  - Polymorphisms affecting the synthesis of aldosterone or its regulation may have
      effects on blood pressure. For example, an autosomal dominant form of human
      hypertension, glucocorticoid suppressible hyperaldosteronism, is caused by
      recombination between the genes for aldosterone synthase (CYP11B2) and steroid 11
      beta-hydroxylase (CYP11B1), creating a chimeric gene in which the CYP11B1
      promoter and CYP11B2-specific coding sequences are juxtaposed. Thus, aldosterone
      synthesis is improperly regulated. We have begun an analysis of the human CYP11B2
      and CYP11B1 genes to see if frequent polymorphisms exist and if they are
      correlated with differences in blood pressure. We have found frequent
      polymorphisms in CYP11B2. One in the promoter influences binding of the
      transcriptional regulatory protein, SF-1. Another is a gene conversion in intron
      2 so that most of the intron has a sequence corresponding to CYP11B1. These
      polymorphisms are in linkage disequilibrium, defining 3 haplotypes. Blacks and
      whites differ significantly (p < 0.001) in the frequency with which these
      haplotypes occur. Further studies are required to determine if the observed
      differences between blacks and whites in blood pressure and in aldosterone levels
      can be explained in part by these allelic differences in CYP11B2 or by other
      polymorphisms in linkage disequilibrium on these haplotypes.

PMID- 7588404
TI  - Cloning of the 11 beta HSD type II enzyme from human kidney.
AB  - The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) converts
      glucocorticoids to receptor inactive metabolites. Two isoforms of the enzyme
      exist. 11 beta HSD1 is a low affinity NADP dependent enzyme, while 11 beta HSD2
      is a high affinity NAD dependent species thought to be responsible for endowing
      specificity on the mineralocorticoid receptor and for protecting the fetus from
      high circulating levels of maternal glucocorticoids. We have recently cloned the
      human renal 11 beta HSD2 enzyme. In this report we show that 11 beta HSD2
      potently inactivates the synthetic glucocorticoid dexamethasone, producing a
      single product thought to be the 11-dehydrodexamethasone metabolite. Sequence
      analysis shows that the new isoform is a member of the short-chain alcohol
      dehydrogenase superfamily (SCAD), most closely related to 17 beta HSD2 and
      distantly related to 11 beta HSD1.

PMID- 7588410
TI  - Aldosterone synthase gene regulation by angiotensin.
AB  - Excessive aldosterone secretion in some hypertensive patients may result from
      abnormal aldosterone synthase (AS) gene regulation in response to changes in
      dietary sodium intake. We have utilized NCI-H295 cells, which exhibit stable
      angiotensin-induced aldosterone secretion, for transient transfections with
      murine AS/human growth hormone reporter constructs. An angiotensin response
      element increasing AS gene transcription during angiotensin stimulation appears
      to reside within the initial 425 nt of the murine AS promoter. We also noted the
      possible presence of a negatively-acting cis element between nt -425 and -1500.
      These studies provide an initial step toward characterizing molecular mechanisms
      by which angiotensin regulates AS gene transcription.

PMID- 7588409
TI  - Expression of cytochrome P450 aldosterone synthase and 11 beta-hydroxylase mRNA
      during adrenal regeneration.
AB  - In situ hybridization histochemistry was used to monitor the expression of
      cytochrome P450 aldosterone synthase (P450aldo) and cytochrome P450 11 beta
      hydroxylase (P45011 beta) mRNA in regenerating rat adrenals. Comparisons were
      made between regenerating adrenals from unilateral enucleated/unilateral
      adrenalectomized (ULE/ULA) and bilateral enucleated (BLE) rats. During the first
      week after enucleation, P45011 beta mRNA was expressed in all adrenals reflecting
      the presence of fasciculata cells; however, P450aldo mRNA was detected only in
      adrenals from ULE/ULA rats suggesting that the glomerulosa cell phenotype was
      absent after BLE. These findings suggest that the expression of glomerulosa cells
      during the early period of regeneration is influenced by the presence of a second
      regenerating adrenal.

PMID- 7588411
TI  - Clinical, biochemical and genetic features of five extended kindred's with
      glucocorticoid-suppressible hyperaldosteronism.
AB  - Glucocorticoid-suppressible hyperaldosteronism (GSH) is an uncommon form of
      dominantly inherited hypertension caused by the inheritence of a chimaeric 11
      beta-hydroxylase/aldosterone synthase gene. Affected individuals appear to have
      an increased risk of premature morbidity and mortality from stroke, but treatment
      with low doses of dexamethasone can completely reverse the biochemical and
      clinical features. We assessed the clinical and genetic features of 5 British
      kindreds with GSH, the largest collection outwith the United States, and
      determined the location of the crossover regions in the chimaeric gene of all 5
      kindreds. All of the kindreds were of celtic origin, another feature peculiar to
      GSH. In total 19 out of 60 individuals screened by genotyping were found to
      possess the chimaeric gene and sequencing of the chimaeric gene revealed that all
      the crossover regions were within the exon 3- exon 4 region of, in keeping with
      previous studies, and three kindreds possessed indistinguishable chimaeric genes.

PMID- 7588408
TI  - Cloning of CYP11B1 and CYP11B2 from normal human adrenal and their functional
      expression in COS-7 and V79 Chinese hamster cells.
AB  - The cDNAs of human 11 beta hydroxylase (CYP11B1) and aldosterone synthase
      (CYP11B2) were cloned from surgically removed normal human adrenal using
      polymerase chain reaction. The cloned cDNAs were transfected into COS-7 cells and
      steroid hydroxylase activity of the two cytochromes P450 expressed was determined
      in order to elucidate their the functional characteristics. Stable expression of
      human CYP11B1 or CYP11B2 was performed in V79 hamster cells and confirmed by
      Southern blotting, Northern blotting, and enzymatic activity. Interestingly,
      recombinant V79 cells were able to support CYP11B1 and CYP11B2 dependent steroid
      conversion without additional heterologous expression of the corresponding
      electron donor system.

PMID- 7588412
TI  - Cortisol: a tool to study aldosterone biosynthesis in rats.
AB  - Corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18OHDOC) but not 11
      deoxycorticosterone (DOC) displaced cortisol (F) specifically bound to rat
      adrenal mitochondria. F. competitively inhibited aldosterone formation from B,
      18OHB and 18OHDOC but did not inhibit conversions of DOC to B or 18OHDOC. High
      concentrations of DOC increased its conversion to 18OHDOC rather than B.

PMID- 7588415
TI  - Studies of the guinea pig adrenal cytochrome P450c17 cDNA.
AB  - Cytochrome P450c17 is a single enzyme that catalyzes two successive reactions
      within the delta 5 and delta 4 pathways. The proteins expressed with human,
      bovine, and rat cDNAs convert both pregnenolone and progesterone into delta 5
      delta 4-C19 steroids, although the rat cDNA prefers the delta 4 pathway. Our
      results showed that the guinea pig adrenal possesses the enzymatic machinery to
      produce C19 steroids and suggest that the lyase activity plays a major role in
      regulating these syntheses. To obtain more information on the structure-function
      relationship we isolated a full-length cDNA clone encoding guinea pig P450c17.
      Northern blots of total RNA extracted from the testis, ovary, and adrenals of the
      guinea pig show that the P450c17 cDNA hybridized with a predicted 1.8-kb mRNA and
      with two other mRNAs of 3 and 4 kb. No signal other than the 1.8-kb mRNA was
      observed in the human adrenocortical NCI-H295 cells. Activation of the cAMP
      dependent protein kinase A pathway increased the levels of the three mRNAs.
      Transfection of vectors expressing guinea pig P450c17 cDNA into nonsteroidogenic
      cells confers 17 alpha-hydroxylase and 17,20-lyase activities, showing that a
      single protein in the guinea pig supports both activities. However, the analysis
      of the enzymatic properties showed that the guinea pig P450c17 recombinant, in
      contrast to the human, supports hydroxylase and lyase activities only with delta
      4 substrates. These results were further confirmed with isolated guinea pig
      adrenocortical cells. Our data demonstrate, first, that guinea pig P450c17 cDNA
      hybridizes with three different transcripts and second, that the expressed
      protein has characteristics associated exclusively with the guinea pig enzyme.

PMID- 7588413
TI  - Metabolism of 11-deoxycortisol by cytochrome P450(11 beta): identification of
      reaction products by 1H-NMR and LC/MS-APCI method.
AB  - A hitherto-unidentified steroid produced in the reaction mixture of 11
      deoxycortisol with bovine cytochrome P450(11 beta) reconstitution system was
      purified by repeated HPLCs, and subjected to 1H-NMR analysis. The result
      suggested that the new metabolite was 19-oxo-11-deoxycortisol. This was further
      confirmed by a new analytical technique using LC/MS equipped with atmospheric
      pressure chemical ion (APCI)-analyzer.

PMID- 7588414
TI  - Variation in the expression of human 3 beta-hydroxysteroid dehydrogenase.
AB  - Polymorphic genetic variation shows that the genes for human 3 beta
      hydroxysteroid dehydrogenases (3 beta-HSD) types I and II are closely linked. The
      type II mutations A82T, S100N and L173R are associated with male
      pseudohermaphroditism and A82T is associated, with variable penetrance, with
      female premature puberty. When expressed in vitro A82T showed less than 5% of
      normal activity and L173R showed a 30-50% reduction in activity. PCR experiments
      and direct genomic cloning show that there is a larger family of 3 beta-HSD
      sequences which require to be tested for expression. The phenomenon of epitopic
      heterogeneity of 3 beta-HSD is discussed and is now shown to apply to testicular
      Leydig cells as well as extrauterine trophoblast. RT-PCR analyses indicate that
      the phenomenon is most likely to be due to post-translational modification
      affecting the carboxytermini 3 beta-HSD types I and II. This phenomenon may
      reflect a further level at which enzyme activity is regulated.

PMID- 7588416
TI  - Transcriptional regulation of the bovine CYP17 gene: two nuclear orphan receptors
      determine activity of cAMP-responsive sequence 2.
AB  - The CYP17 gene contains in its promoter region at least two cis-acting elements
      (cAMP-responsive sequence 1 and 2, CRS1 and CRS2) that are necessary for
      adrenocorticotropin (ACTH) induced transcription. The CRS2 element contains a 6
      bp repeat similar to binding sites for members of the nuclear hormone receptor
      superfamily of transcription factors. We present data that establish the repeated
      part of CRS2 (repCRS2) as a target of two nuclear orphan receptors; steroidogenic
      factor 1 (SF-1) and chicken ovalbumin upstream promoter transcription factor
      (COUP-TF). The repCRS2 element was found to form COUP-TF-related complexes with
      nuclear extracts from all cell lines tested, whereas SF-1-related complexes were
      only formed with extracts from steroidogenic Y1 cells. Transfection studies of
      steroidogenic cells demonstrated that SF-1 acts as an activator of repCRS2
      dependent transcription of reporter genes.

PMID- 7588419
TI  - Type beta 1 transforming growth factor is an inhibitor of 3 beta-hydroxysteroid
      dehydrogenase isomerase in mouse adrenal tumor cell line Y1.
AB  - In the Y1 mouse adrenal tumor cell line, the 3 beta-hydroxysteroid dehydrogenase
      isomerase enzyme (3 beta-HSD) which catalyzes the transformation of 3 beta
      hydroxy-5-ene steroids to 3-keto-4-ene steroids is active. The effect of type
      beta 1 transforming growth factor (TGF beta 1), a potent modulator of
      adrenocortical differentiated functions, on the 3 beta-HSD enzyme was studied.
      Four isoforms of 3 beta-HSD yielding proteins of different mobility on SDS-PAGE
      were previously detected in the mouse; whereas only one form was present in the
      mouse adrenal, we detected two isoforms in the Y1 cells. An inhibition of the
      basal enzymatic activity was observed after TGF beta 1 treatment which was
      correlated with a decrease in 3 beta-HSD protein (both isoforms) and mRNA levels.

PMID- 7588418
TI  - Acetylcholine induces oscillations in intracellular calcium in isolated bovine
      adrenal zona fasciculata/reticularis cells.
AB  - The effects of acetylcholine (ACh) on intracellular free calcium were studied in
      primary cultures of purified bovine adrenal zona fasciculata/reticularis (ZFR)
      cells. In fura-2 loaded single cells, concentrations of ACh which stimulated
      cortisol secretion and phosphoinositol production were found to promote an
      increase in free cytosolic calcium ([Ca2+]i). This response was heterogeneous,
      showing either (i) an initial increase in [Ca2+]i followed by a fall to a level
      above that in unstimulated cells, or (ii) an initial increase followed by
      oscillations about the original resting level or a higher resting level. The
      frequencies of [Ca2+]i oscillations to ACh showed a dose-dependent trend. The
      sustained [Ca2+]i oscillations were abolished by the muscarinic antagonist
      atropine, or by removal of extracellular Ca2+. These data demonstrate for the
      first time in adrenocortical cells that: (i) ACh can induce [Ca2+]i oscillations
      in single ZFR cells; (ii) these oscillations occur in a dose-dependent manner;
      (iii) the sustained oscillatory phase is dependent on influx of extracellular
      Ca2+. Thus, like cells of the zona glomerulosa, bovine ZFR cells are also capable
      of sustained dose-dependent oscillatory responses to agonists which activate
      phosphoinositidase C.

PMID- 7588421
TI  - Regulation and function of the fetal adrenal gland in sheep.
AB  - It is now known that in some species (sheep, cow, pig, llama) the fetal adrenal
      cortex is capable of secreting cortisol both early and late in gestation, but not
      during some, variable, intermediate time period. In the sheep the fetal adrenal
      can secrete cortisol, and respond quickly to ACTH, both between 40-90 days of
      gestation, and from 120-150 days (term), but not between 90-120 days. The
      inability to secrete cortisol in this 'off' period is due to lack of adequate
      pituitary ACTH at this time to maintain expression of P-450(17 alpha and P
      450scc. Recent experiments demonstrate that the fetal pituitary does secrete
      adequate amounts of ACTH to keep these genes expressed, in the 40-90 day period.
      The question now becomes, therefore, what regulates the triphasic secretion
      pattern of ACTH during fetal sheep development.

PMID- 7588420
TI  - Immunohistochemical evaluation of the cellular localization and ontogeny of 3
      beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in the human fetal adrenal
      gland.
AB  - The enzyme, 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase (3 beta-HSD)
      is an essential element in the biosynthetic pathway for potent adrenal steroid
      hormones that appear to regulate maturation of many tissues in utero and are
      critical for homeostasis after birth. The results of prior studies are suggestive
      that 3 beta-HSD activity in the human fetal adrenal (HFA) is very low and
      restricted to the outer zone of cortical cells, the neocortex (NC), during mid
      gestation. Near the time of birth, however, there must be enhanced expression of
      this enzyme to allow for adaptation to extrauterine life. In the present study,
      we sought to characterize, by use of immunohistochemical methods, the cellular
      localization and developmental changes of 3 beta-HSD in the HFA during the
      interval of 11-41 wks gestation. Early in gestation, 11-15 wks, we noted
      considerable 3 beta-HSD in NC and in occasional fetal zone (FZ) cells as well.
      Thereafter until 24-25 wks, 3 beta-HSD was very low in NC cells and virtually
      absent from the FZ. Throughout the third trimester, the outer 1/2-2/3 of the NC
      was increasingly immunostained and clusters of immunoreactive cells also appeared
      near the central medullary vein of the adrenal. The NC cells and those located in
      the cortical cuff region that expressed 3 beta-HSD resembled zona glomerulosa
      cells. Among many other fetal tissues studied, only testicular Leydig cells
      (18,19 wks) and hilar cells of the ovary (26 wks) were found to contain 3 beta
      HSD in quantities sufficient to be detected by immunohistochemistry. These
      results are suggestive of a heretofore undocumented stimulus to 3 beta-HSD in the
      HFA in early gestation followed by a suppression of the adrenal concentration of
      this enzyme during mid-gestation. High levels of 3 beta-HSD in early development
      may facilitate cortisol production, which is believed to play a role in
      differentiation of the medullary precursors during this developmental period. The
      control of adrenal 3 beta-HSD during human fetal development may be more complex
      than initially envisioned and requires further study.

PMID- 7588422
TI  - In vivo studies of the control of DNA synthesis in the rat adrenal cortex and
      medulla.
AB  - The control of zonation in the adrenal cortex has been studied by measuring DNA
      synthesis using an analogue of thymidine, bromodeoxyuridine (BrDUrd). Groups of
      rats were infused with BrDUrd for 10-14 days whilst being treated with: high or
      low sodium diets; captopril; angiotensin II; dexamethasone; an inhibitor of
      nitric oxide synthesis, L-NAME. DNA synthesis in the zona glomerulosa was
      increased by low sodium food and angiotensin and was decreased by dexamethasone,
      captopril L-NAME and a high sodium diet. Dexamethasone, not manipulations of the
      renin-angiotensin system, affected DNA synthesis in the outer zona fasciculata.
      The BrDUrd index in the zona intermedia was unaffected by any of the treatments
      and was generally lower than in adjacent zona fasciculata and zona glomerulosa
      cells. Cells of the zona reticularis appeared to be regulated independent of the
      zona fasciculata. BrDUrd uptake in nuclei of the adrenal medulla was inversely
      related to blood pressure. We conclude that DNA synthesis in each adrenocortical
      zone is independently controlled. Migration of cells within zones after
      proliferation is likely.

PMID- 7588417
TI  - A cell-specific nuclear receptor plays essential roles in adrenal and gonadal
      development.
AB  - Recent analyses of the cytochrome P450 steroid hydroxylases have established a
      key role for an orphan nuclear receptor, designated steroidogenic factor 1 (SF
      1), in their coordinate, cell-selective expression. SF-1 was proposed to regulate
      the steroid hydroxylases by interacting with shared promoter elements in their 5'
      flanking regions. During mouse embryonic development, SF-1 was expressed from the
      earliest stages of organogenesis of the steroidogenic tissues, suggesting a key
      role in steroidogenic cell differentiation. Finally, disruption of the gene
      encoding SF-1 revealed its essential function in the development of the adrenal
      glands and gonads and in pituitary gonadotrope function. These studies suggest
      that SF-1 acts at multiple levels of the reproductive axis to maintain
      reproductive competence.

PMID- 7588423
TI  - Bacterial lipopolysaccharide stimulates glucocorticoid secretion in
      hypophysectomized rats.
AB  - The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial
      lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone
      (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats.
      Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after
      the injection. The stress evoked by the vehicle i.p. injection provoked
      significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but
      not in Hx animals. In intact rats, LPS enhanced (over the respective control
      value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at
      120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised
      B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was
      completely annulled, in both intact and Hx rats, by the simultaneous
      administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting
      peptide that are competitive inhibitors of CRH and ACTH, respectively. The
      hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis
      in rats, by stimulating not only the central (hypothalamo-pituitary), but also
      the peripheral (intra-adrenal) branch of the CRH/ACTH system.

PMID- 7588424
TI  - Blunted adrenarche in patients with classical congenital adrenal hyperplasia due
      to 21-hydroxylase deficiency.
AB  - Dehydroepiandrosterone sulfate (DHEAS) concentration levels were measured by a
      specific RIA in 23 female and 7 male patients with classical congenital adrenal
      hyperplasia (CAH) salt-losing type due to steroid 21-hydroxylase (21-OH)
      deficiency. The patients were divided into four groups by age and the DHEAS
      concentrations (mean +/- SD; micrograms/dl) for each age group were: 5 to 8 years
      (10.2 +/- 6.5; range 5-23 micrograms/dl); 8 to 10 years (18.3 +/- 14.9; range 5
      44 micrograms/dl); 10 to 18 years (41.9 +/- 40; range 5-160 micrograms/dl); and
      above 18 years (49.7 +/- 65.9; range 9 to 242 micrograms/dl). These DHEAS levels
      were compared to age-matched normal values and it was found that DHEAS
      concentrations in 29 of the 30 patients were less than or in the lower part of
      the normal range for all age groupings. The DHEAS levels did not correlate with
      17 alpha-hydroxyprogesterone (17-OHP), androstenedione, and testosterone values.
      The data indicate that blunted adrenarche occurs in classical CAH patients with
      21-OH deficiency.

PMID- 7588425
TI  - Melatonin modifies prolactin release induced by opiate antagonists in male rats.
AB  - The effect of melatonin on the prolactin (PRL) release induced by treatment with
      naloxone, naloxone methyliodide, naltrexone and nalmefene were studied in adult
      male rats. Subcutaneous melatonin injection (1.4 mg/Kg) had no significant effect
      on serum PRL levels, but decreased by 29% and 26% respectively the inhibitory
      effect potency of naltrexone (2.5 mg/Kg) and nalmefene (2 mg/Kg) on PRL secretion
      after simultaneous injections. The inhibitory effect potency of naloxone on PRL
      release increased (16%) when it was administered with melatonin. Simultaneous
      injection of melatonin with naloxone methyliodide (2.8 mg/Kg) inhibited PRL
      release (77.5%) while naloxone methyliodide alone did not modify this secretion.
      The results obtained with a quaternary opioid antagonist indicate that the opioid
      receptor type which mediates PRL response is located inside the blood-brain
      barrier. Our findings show that opiate antagonists and their quaternary ammonium
      salts affect secretion of PRL through mechanism susceptible to the influence of
      melatonin.

PMID- 7588426
TI  - Anti 70 kDa heat shock protein antibodies in sera of patients affected by
      autoimmune and non-autoimmune thyroid diseases.
AB  - Twenty eight patients (25F, 3M) affected by autoimmune and non-autoimmune thyroid
      diseases were studied. HSP 70 antibodies were present in 21.4% of patients. Five
      of them were affected by Graves' disease and one by De Quervain's thyroiditis.
      The HSP 70 antibodies mean values of patients were significantly higher than the
      normals (p < 0.05). This datum was confirmed by Western blotting. The presence of
      HSP 70 antibodies in the sera of those patients may support the link between the
      protein and the thyroid autoimmune processes.

PMID- 7588427
TI  - Hexarelin, a novel GHRP-6 analog, counteracts the inhibitory effect of
      hydrocortisone on growth hormone secretion in acromegaly.
AB  - Hexarelin (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 analog with the
      substitution of D-tryptophan with its 2-methyl derivative. The aim of our study
      was to ascertain whether hexarelin was able to counteract the glucocorticoid
      mediated increase in hypothalamic somatostatin tone and consequent inhibition on
      serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age
      range 27-71 years; BMI range 23.3-35 kg/m2) with active acromegaly underwent: 1)
      hydrocortisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in
      2 mL saline, at time -60 followed by a 120 min iv infusion of 250 mg
      hydrocortisone succinate in 250 mL saline, from -60 to 60 min; 2)
      hexarelin+hydrocortisone: a bolus iv injection of hexarelin 100 micrograms, 60
      min after initiation of a 2-hour hydrocortisone infusion; 3) hexarelin alone: a
      bolus iv injection of hexarelin at time 0, 60 min after initiation of a 2-hour
      saline infusion. The mean GH peak, expressed as percent change with respect to
      baseline level (mean of -75 and -60 minute samples), after hexarelin (1750 +/-
      1157%) did not differ significantly with respect to that observed after
      hexarelin+hydrocortisone (1120 +/- 770%). After hydrocortisone alone the patients
      showed a mean decrease in GH levels as compared to baseline levels, of 47 +/- 7%.
      Our data show that the GH response to hexarelin in acromegaly is resistant to the
      inhibitor action of an acute and sustained elevation of serum cortisol levels.
      That hexarelin counteracts the glucocorticoid-mediated inhibition of GH secretion
      supports the hypothesis of an hexarelin-induced decrease in endogenous
      somatostatin tone.

PMID- 7588429
TI  - Inhibin is present in the corpus luteum of pseudopregnant rats and can interact
      with progesterone to inhibit resumption of estrous cycles.
AB  - The corpora lutea (CL) of ovaries of adult pseudopregnant (PSP) rats were stained
      by immunohistochemistry for inhibin alpha subunit using sheep alpha-chain1-27
      antibody as a measure of inhibin content. Staining was light in estrous cycle CL
      (stage III), increased in Day 2 and Day 4 PSP CL and reached maximal density on
      day 6 PSP when both large cells and many small cells stained. Staining was
      decreased in CL from 8 and 10 day PSP. Granulosa cells of growing follicles
      showed light stain on days 8 and 10 of PSP. Adult female rats were treated for 5
      days beginning at estrous cycle Stage III (cornified masses). In Experiment 1,
      three groups of rats were used: 1. implanted with 30mm progesterone capsules and
      injected with saline, 2. implanted with 30mm progesterone capsules and injected
      with 10 ng rh inhibin A daily, 3. implanted with empty capsules and injected with
      10 ng rh inhibin A daily. Both groups of rats with progesterone implants had
      significantly slower return of cycling after removal of the capsules than did the
      rats injected with 10ng rh inhibin A alone. In Experiment 2, the same treatments
      were given except that 20ng of rh inhibin A (10ng 2x/day) was given to both
      inhibin treatment groups. Rats treated with progesterone and 20ng inhibin had a
      significantly slower return of cyclic activity (4.4 days) over that found in the
      other two treatment groups. We conclude that the absence of cyclic activity in
      PSP rats is possibly due to the secretion of both inhibin and progesterone by the
      CL.

PMID- 7588428
TI  - Effects of GLP-1 and 2,5-anhydro-D-mannitol on insulin secretion and plasma
      glucose in mice.
AB  - The truncated glucagon-like peptide-1 (GLP-1(7-36)amide or GLP-1) stimulates
      insulin secretion, enhances glucose elimination and is of potential interest in
      diabetes treatment. We studied the hypoglycemic action of GLP-1 in normal mice
      when given alone or together with the fructose analogue, 2,5-anhydro-D-mannitol
      (2,5-AM), which inhibits glycogenolysis and gluconeogenesis. GLP-1 (32 nmol/kg
      iv) lowered plasma glucose levels after 25 min to 4.6 +/- 0.2 mmol/l compared
      with 7.3 +/- 0.4 mmol/l in controls (P < 0.001). Also 2,5-AM (0.5 mumol/kg iv)
      reduced plasma glucose levels, to 5.6 +/- 0.3 mmol/l (P < 0.01). When given
      together, the glucose lowering action of GLP-1 and 2,5-AM was additive, since the
      25 min glucose level was 2.8 +/- 0.2 mmol/l. At 5 min after injection, GLP-1 had
      increased plasma insulin levels to 693 +/- 68 pmol/l compared with 342 +/- 42
      pmol/l in controls (P < 0.01). 2,5-AM abolished this increase. Furthermore, GLP-1
      (32 nmol/kg) did not affect the glycogen content, neither in the liver nor in the
      gastrocnemic muscle in samples taken at 30 min after injection. Moreover, in
      isolated islets incubated at 3.3 and 8.3 mmol/l glucose, 2,5-AM at 75 mmol/l
      inhibited glucose-stimulated insulin secretion (P < 0.05) showing that 2,5-AM
      inhibits insulin secretion both in vivo and in vitro. We conclude that GLP-1 may
      reduce plasma glucose levels also to levels below the basal levels under normal
      conditions, and that an insulin- and liver-independent action of the peptide
      contributes to its hypoglycemic action in normal animals.

PMID- 7588430
TI  - Influence of progesterone and its antagonist mifepristone (RU 486) on collagen
      content in uterine cervix in pregnant rats.
AB  - Total collagen and its soluble fraction as well as water content were determined
      in late pregnancy in the uterine cervix in a population of 36 rats treated with
      progesterone (n = 10), mifepristone (n = 13) and controls (n = 13). In both
      treated groups there were no signs of delivery on the 21st day of gestation.
      Water content was significantly lower in the mifepristone-treated group. A
      statistically higher soluble collagen fraction was observed in this group. The
      results obtained in the progesterone-treated group were not significantly
      different when compared to the controls. Significant differences were observed
      between progesterone- and mifepristone-treated groups in total and soluble
      fractions of collagen.

PMID- 7588431
TI  - Cyclosporin A, rapamycin and FK506 decrease prolactin release from rat pituitary
      cells in primary culture.
AB  - It is at present well established that prolactin exerts a non-specific
      immunoactivating function. In this work we tested whether the immunosuppressant
      drugs cyclosporin A, FK506 and rapamycin influence prolactin release from rat
      pituitary cells in primary culture. The tested drugs had no effect on the
      prolactin release measured during a 2h incubation period, indicating that they do
      not influence the secretion of prolactin from intracellular stores into the
      culture medium. During longer incubation times (48h), however, prolactin release
      was diminished to 56% +/- 18 (10 microM cyclosporin A), 64% +/- 14 (1 microM
      rapamycin) or 64% +/- 7 (1 microM FK506), suggesting an effect on prolactin
      production. At these drug concentrations no toxic effects were observed. The data
      indicate that inhibition of pituitary prolactin synthesis might contribute to the
      immunosuppressant action of cyclosporin A, rapamycin and FK506.

PMID- 7588432
TI  - Estrogen receptors in parotid tumors.
AB  - A regulatory role for estrogen in the growth of salivary gland tumors has been
      hypothesized. In the current study we attempted to establish whether or not
      benign and malignant parotid tumor cells express estrogen receptors.
      Immunohistochemical studies were performed with samples of tissue from 72
      patients with benign tumors and 26 patients with malignant tumors originating in
      the parotid gland. Replicate tissue sections were stained with two sets of
      reagents specific for the receptors. There was no immunohistochemical evidence
      for the presence of estrogen receptors in any specimen examined. In contrast,
      cells in tissue sections from a breast cancer control were consistently positive
      for estrogen receptor using the same techniques. These observations show that the
      estrogen receptor concentration in parotid tumors is below the level required for
      visualization by immunohistochemical techniques. Thus, it is unlikely that this
      receptor plays a major role in regulating parotid tumor growth.

PMID- 7588433
TI  - Serum concentrations of osteocalcin in pregnant women with multinodular thyroid
      goiter undergoing treatment with levothyroxine.
AB  - In this study we measured serum osteocalcin (Bone Gla-Protein) to investigate
      bone metabolism in pregnant women with multinodular thyroid goiter undergoing
      treatment with levothyroxine (L-T4). Serum concentration of BGP was measured in
      18 pregnant women and in 20 non-pregnant women (ages raging from 21-34 years)
      receiving L-T4 (75-125 micrograms/day). Venous blood samples for RIA
      determination of serum BGP, plasma thyroid hormone (T3, T4, free T3, free T4) and
      TSH were collected from the two groups. The samples of the pregnant women group
      were collected before pregnancy (at the moment the disease was diagnosed without
      L-T4 therapy) during pregnancy (at the 3rd, 6th and 9th month) and one month
      after delivery. The normal TSH levels (measured with Irma method) before
      pregnancy, were significantly reduced during treatment with L-T4 during pregnancy
      and after delivery (p < 0.005), respectively. Also in the control group TSH
      levels were reduced during treatment. Serial measurement of serum BGP before
      pregnancy, (3.4 +/- 1 ng/ml) during pregnancy (3rd: 4.2 +/- 1.5 ng/ml; 6th: 4.2
      +/- 1.4 ng/ml; 9th: 2.8 +/- 1.6 ng ml, month respectively) and one month after
      delivery (3.5 +/- 1.3 ng/ml) did not demonstrate significant variations.
      Furthermore, in the control group the BGP levels were 3.2 +/- 1.7 ng/ml. There
      was no correlation between BGP, thyroid hormones and TSH in these groups. These
      data indicate that the administration of moderate doses of L-T4 in pregnant and
      in non-pregnant women did not modify the serum BGP levels.

PMID- 7588434
TI  - Failure of ethanol metabolites to alter gonadotropin secretion or luteinizing
      hormone synthesis in vitro.
AB  - The impact of ethanol on the male reproductive axis are multiple and varied, with
      both gonadal and control hypothalamic-pituitary pertubations being reported.
      There appears to be a discrepancy, however, between the in vivo and in vitro
      effects of ethanol on hypothalamic luteinizing hormones releasing hormone (LHRH)
      and the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating
      hormone (FSH). While in vivo data suggests a decrease in LHRH release after EtOH,
      in vitro studies find no effect on secretion. Similarly, in vivo acute EtOH
      profoundly diminishes LH synthesis and secretion, while in vitro impaired release
      with no alteration in the transcription of beta LH has been found. A potential
      exploration for these discrept results could be the in vivo metabolism of EtOH
      into acetaldehyde and acetate, or the subsequent formation of salsolinol, a
      product of acetate combining with dopamine. To test this possibility, a series of
      in vitro experiments were conducted exposing dispensed anterior pituitary cells
      from male rats to different doses of acetaldehyde, acetate or salsolinol for
      varying amounts of time for which gonadotropin secretion and beta LH mRNA levels
      were assessed. The results demonstrated no effect of either acetaldehyde or
      acetate on basal or LHRH stimulated LH release, FSH release or steady-state beta
      LH mRNA levels. These data suggest that the metabolites of EtOH, which occur in
      vivo but not in vitro, are not responsible for the discrepant gonadotropin
      changes reported between the in vivo and in vitro setting. Other potential
      mechanisms to explain this phenomenon include differences in the molarity of
      EtOH, hyperprolactinemia and suprapituitary influences including hypothalamic
      LHRH, catecholamines, excitatory amino acids, substance P and beta endorphin.

PMID- 7588435
TI  - Effects of domoic acid on serum levels of TSH and thyroid hormones.
AB  - The actions of Domoic Acid (Dom), a marine toxin, on the levels of serum TSH and
      thyroid hormones (T4 and T3) has been studied to determine if these actions could
      be mediated by the serotoninergic system. In all the experiments, adult male
      Wistar rats were used. The Dom dissolved in saline was administered via i.p. in
      doses of 0.5 and 1 mg/kg. The T4 and T3 concentrations were determined by
      enzimoinmunoassay and TSH concentration was determined by radioinmunoassay. The
      results show that Dom 1 mg/kg increases the serum T4 levels one hour after
      treatment and decreases these levels 2 and 3 hr after treatment. Dom 0.5 mg/kg
      decreased the serum T4 levels 2 and 3 hr after treatment. The concentrations of
      T3 in serum were unchanged by both doses of Dom. The concentration of TSH was
      increased by Dom. In order to study the possible mediation of the serotoninergic
      system in the effect of Dom on the hormone levels, PCPA, a tryptophan hydroxylase
      inhibitor, was administered i.p. 90 min before blood sampling. In this case, with
      both doses of Dom a decrease in the levels of both hormones occurred with respect
      to the PCPA group. These results indicate that the serotoninergic system could
      affect the actions of Dom on TSH and thyroid hormone secretion.

PMID- 7588436
TI  - Effect of melatonin on the maintenance of cholesterol homeostasis in the rat.
AB  - The effect of melatonin on cholesterol metabolism in the rat was investigated in
      the dietary and hypothyroid models of hypercholesterolemia. In normal and dietary
      hypercholesterolemia (induced by 1% cholesterol, 0.5% bile acid), melatonin
      treatment (12.5mg/kg i.p.) reduced total serum cholesterol concentration and
      total low density lipoprotein (VLDL+LDL) cholesterol. The protective action of
      melatonin was manifested only following the induction of cholesterolemia in such
      animals. Enhanced catabolism of cholesterol to bile acids is likely involved as
      shown by an increase in fecal bile acid excretion following melatonin treatment.
      Incorporation of 1-14C acetate into sterols was unaffected by melatonin treatment
      which suggests its lack of influence on sterol biosynthesis. In secondary
      hypercholesterolemia (hypothyroidism induced by 2-thiouracil), melatonin exerted
      a beneficial effect by increasing the HDL/total LDL cholesterol ratio. These
      findings suggest that the hypocholesterolemic effect of melatonin may work
      through the augmentation of endogenous cholesterol clearance mechanisms. This is
      accompanied by the lowering of the cholesterol fraction associated with low
      density lipoproteins.

PMID- 7588437
TI  - The binding of recombinant human relaxin to human spermatozoa.
AB  - Porcine relaxin has been reported to stimulate various human sperm functions. In
      this paper we report that human recombinant relaxin binds to human sperm with a
      high affinity (Kd = 6.5 x 10(-10)). The bound 125I-relaxin was not displaced by
      insulin, or human chorionic gonadotropin, however, it was displaced by unlabeled
      relaxin. In sperm function studies, recombinant human relaxin stimulated sperm
      motility, zona-free hamster egg penetration, and the acrosome reaction.

PMID- 7588438
TI  - Effects of calcium channel blockade on mammalian lung branching morphogenesis.
AB  - The bronchial tree is formed during the pseudo-glandular stage of lung
      development in a process termed lung branching morphogenesis. Coinciding with the
      period of lung branching morphogenesis is the appearance of spontaneous airway
      contractions, a phenomenon whose role in development remains unclear. In this
      study, an in vitro model of murine lung branching morphogenesis was used to
      examine the potential role of airway contractions in airway branching and lung
      growth. Spontaneous airway contractions of the proximal airways were observed in
      cultured murine lungs (obtained at 11 days of gestation) after 48 h in culture.
      Airway contractility was inhibited in a reversible manner by the voltage
      dependent calcium channel blocker Nifedipine. Interestingly, long-term incubation
      of lung rudiments with Nifedipine not only prevented airway contraction, but also
      caused lung hypoplasia. The Nifedipine-treated hypoplastic lungs showed a normal
      branching pattern, suggesting that airway contractions and calcium channel
      function are not necessary for cleft formation directly. These observations
      suggest that calcium ion transport is necessary for development of airway
      contractions and for normal progression of lung growth.

PMID- 7588439
TI  - Differential susceptibility to ozone-induced airways hyperreactivity in inbred
      strains of mice.
AB  - Individuals with heightened airways reactivity, such as asthmatics, may be at
      risk to inflammatory effects of oxidant air pollutants. In the inbred mouse,
      significant interstrain variation in airways reactivity to acelycholine (ACh) and
      differential susceptibility to ozone (O3)-induced airways inflammation has been
      described previously. This study used these murine models to test hypotheses that
      (1) O3-induced hyperreactivity to ACh is a function of inherent baseline ACh
      reactivity, and (2) susceptibility to O3-induced inflammation is associated with
      O3-induced hyperreactivity. Strains (15-25 g, 6-8 weeks) with HYPERREACTIVE
      (DBA/2J, AKR/J, A/J), HYPOREACTIVE (C3H/HeJ, C57BL/6J, SJL/H), or INTERMEDIATE
      (129/J) phenotypes for ACh reactivity were exposed for 3 h to 2.0 ppm O3 or air
      (control). ACh reactivity (25 and 50 micrograms/kg, IV) was assessed 0 and 24 h
      after exposure. Relative to air controls, mean airways responses to 25 and 50
      micrograms/kg ACh 24 h post-O3 increased significantly in the HYPERREACTIVE A/J
      strain (p < .05). Among HYPOREACTIVE strains, O3 significantly (p < .05)
      increased the response to 50 micrograms/kg ACh in C57BL/6J and SJL/J strains 24 h
      postexposure. A/J, C57BL/6J, and SJL/J mice are susceptible to O3-induced lung
      injury. O3 did not alter ACh reactivity in the other strains. O3 also did not
      affect airways reactivity to methacholine or carbachol, observations consistent
      with the hypothesis that O3-induced hyperreactivity to ACh may be due, in part,
      to O3 effects on cholinesterase function. Treatment of C57BL/6J and A/J mice with
      an immunosuppressant (cyclophosphamide) or an anti-PMN antibody significantly (p
      < .05) attenuated circulating and infiltrating polymorphonuclear leukocytes
      (PMNs), but did not affect O3-induced hyperreactivity. Therefore, O3-induced ACh
      hyperreactivity was not a function of baseline reactivity, but correlated with
      susceptibility to acute O3-induced airways injury and inflammation. Pharmacologic
      studies suggest that although PMNs were associated with O3-induced
      hyperreactivity, these cells were not the cause of the effect, and that these two
      events are not codependent.

PMID- 7588440
TI  - Dispersion of aerosol particles in an airway cast of a dog.
AB  - Aerosol bolus dispersion was measured in the first branching generations of a
      replicate hollow cast. The cast was made from a solid cast of a beagle-dog
      tracheobronchial tree. The dispersion was measured after penetration of boluses
      into different volumetric depths, with different particle sizes and flow rates
      into the cast. An enhanced flow rate led to a decreasing dispersion in the cast.
      Particle size up to about 4 microns has no significant effect on dispersion.

PMID- 7588441
TI  - Regulation of the beta 2-adrenergic receptor and its mRNA in the rat lung by
      dexamethasone.
AB  - Glucocorticoids increase beta 2-adrenergic responsiveness and receptor density in
      the lung, but the underlying mechanisms have not been clearly elucidated. To
      determine whether changes in beta 2-adrenergic receptor gene expression are
      involved in vivo, we measured beta 2-adrenergic receptor mRNA levels and beta 2
      adrenergic receptor density in lungs from Sprague-Dawley rats treated with a
      daily injection of dexamethasone (1 mg/kg subcutaneously) for 1, 3, or 7 days.
      Animals were sacrificed either 2 or 24 h after receiving the last injection. beta
      2-Adrenergic receptor mRNA levels were significantly (p < .05) elevated compared
      to saline-treated controls in the lungs of animals sacrificed 2 h after
      dexamethasone injection for 1 day (174 +/- 12%), 3 days (236 +/- 18%), and 7 days
      (220 +/- 11%). Receptor mRNA levels measured 24 h after dexamethasone injection
      did not differ significantly from the control group. Induction of beta 2
      adrenergic receptor mRNA by dexamethasone was transient, since no significant
      cumulative or sustained increase in receptor mRNA levels was observed during the
      study period. Treatment with dexamethasone increased beta 2-adrenergic receptor
      density as expected, but no significant increase in receptor density was detected
      until 24 h after the third daily injection of dexamethasone, when levels reached
      2045 +/- 150 fmol/mg protein compared to 1292 +/- 34 fmol/mg protein in the
      control group. Receptor density then remained at this elevated level through 7
      days of treatment. These results show that dexamethasone up-regulates both the
      beta 2-adrenergic receptor and its mRNA in vivo in the lung. The induction of
      beta 2-adrenergic receptor mRNA levels indicates that glucocorticoids may
      regulate receptor density in the lung through modulation of gene expression.
      However, the difference between the time course of induction for the beta 2
      adrenergic receptor and its mRNA suggests that additional translational or post
      translational mechanisms may also be involved.

PMID- 7588442
TI  - Effect of flow rate on aerosol bolus penetration in a hollow canine lung airway
      cast.
AB  - A cast of dog tracheobronchial airways, which is complete to airways of 1 mm in
      diameter, was used for experimental studies of the effect of flow rate on aerosol
      bolus penetration during a tidal breath. Aerosol boli of 35 cm3 were injected
      during a 1-L inhalation of air. The recoveries of aerosol particles in expired
      air were measured after various breathholding times. The results show that the
      penetration depth of an aerosol bolus increases with decreasing flow rate,
      especially for flow in transition from a flat profile to a parabolic profile.

PMID- 7588444
TI  - Monoclonal antibodies to surfactant protein D: evaluation of immunoreactivity in
      normal rat lung and in a radiation-induced fibrosis model.
AB  - This report describes the development of a new panel of monoclonal antibodies
      established after immunization of mice with purified surfactant protein D of the
      rat. To enhance the detection of SP-D in formalin- or Schaffer-fixed samples,
      immunohistochemistry was performed by using microwave pretreatment of paraffin
      sections. Using these new antibodies that bind to type II epithelial cells, Clara
      cells, and alveolar macrophages, the responses of lung parenchymal cells were
      examined in a radiation-induced fibrosis model. Increased accumulation of
      extracellular SP-D in the alveolar space was found. Double staining with anti
      surfactant protein A antibodies revealed different Clara cell populations
      containing one or both types of surfactant proteins.

PMID- 7588443
TI  - Characterization of proteoglycans produced by rat pleural mesothelial cells in
      vitro.
AB  - The mesothelial cell envelopes the surface of the parietal and visceral pleura.
      These cells are known to synthesize most of the protein constituents of the
      pleural basement membrane and interstitium. This study examined the ability of a
      rat pleural mesothelial cell line to synthesize proteoglycans in vitro. Cells
      were labeled with inorganic 35SO4 to label the glycosaminoglycan moiety of
      proteoglycans. The medium and combined cell membrane/extracellular matrix
      fractions contained 73 and 25% of the proteoglycan radioactivity, respectively.
      The medium contained a single chondroitin/dermatan sulfate proteoglycan of
      approximately 190 kDa, consistent with biglycan. As determined by Northern
      analysis of steady-state levels of messenger RNA, the cells contained message for
      biglycan. Stimulation of the cells with epidermal growth factor resulted in the
      appearance of a second chondroitin/dermatan sulfate proteoglycan of approximately
      97 kDa, characteristic of decorin. The cell membrane/matrix contained a biglycan
      like chondroitin/dermatan proteoglycan and several heparan sulfate proteoglycans.
      Pleural mesothelial cells in vitro are capable of synthesizing a variety of
      interstitial and basement membrane proteoglycans.

PMID- 7588445
TI  - Pulmonary O2 toxicity: role of endogenous tumor necrosis factor.
AB  - The role of endogenous tumor necrosis factor (TNF) in the pathogenesis of
      pulmonary O2 toxicity was investigated. Intratracheal insufflation of anti-TNF
      antibodies prolonged the survival of rats exposed to 100% O2. No TNF bioactivity
      or immunoreactive protein was detectable in the alveolar lavage fluid or lung
      homogenate of rats exposed to normoxia or hyperoxia. However, levels of pulmonary
      TNF mRNA were markedly enhanced in rats exposed to hyperoxia. These results
      suggest that hyperoxia may cause the production of low level TNF, which in turn
      enhances O2 toxicity.

PMID- 7588446
TI  - Increased immunoreactive rat lung ICAM-1 in oleic acid-induced lung injury.
AB  - Levels of immunoreactive ICAM-1 in rat lung were followed during the kinetic
      development of acute oleic acid-induced lung injury in the rat by the ELISA
      assay. Significant increases in ICAM-1 immunoreactivity were found on rat lung
      membranes within 30 min of oleic acid injection. The increased immunoreactive
      ICAM-1 persisted for the duration of the study (4 h) and paralleled lung injury
      as measured by decreased lung compliance. Enhanced ICAM-1 immunofluorescence was
      also observed on cryostat sections of lungs from oleic acid-treated rats. No
      direct effect of oleic acid on ICAM-1 levels of cultured human umbilical vein
      endothelial cells or rat lung microvascular endothelial cells was observed. This
      suggests that either oleic acid raises rat lung ICAM-1 levels on endothelial
      cells by an indirect mechanism or that oleic acid increases ICAM-1 levels on
      other cell types, such as fibroblasts or lung epithelial cells, by direct or
      indirect mechanisms. Some of the increased ICAM-1 may also be due to the
      accumulation of ICAM-1 containing circulating leukocytes in the lung. The role of
      ICAM-1 in the pathophysiology of oleic acid-induced lung injury and the mechanism
      by which oleic acid increases ICAM-1 expression in the lung therefore remain to
      be defined by future experimentation.

PMID- 7588448
TI  - Influences of tobacco smoke and vitamin E depletion on the distal lung of
      weanling rats.
AB  - Tobacco smoke is associated with pulmonary emphysema via elastase-antielastase
      and oxidant-antioxidant imbalance. This study addressed the tobacco smoke-induced
      changes in the lungs of weanling rats with vitamin E depletion. Three-week-old
      Wistar rats fed on vitamin E-depleted or normal diet were intermittently exposed
      to tobacco smoke by Hamburg II machines for 4 weeks. Tobacco smoke significantly
      suppressed body weight increases, particularly in the vitamin E-depleted group.
      In the normal diet group, tobacco smoke induced emphysematous changes with
      significant increases in the mean linear intercept (Lm) and the destructive index
      (DI), which was supported by an increase in elastase-like activity and a decrease
      in elastase inhibitory capacity (EIC) in bronchoalveolar lavage (BAL) fluid.
      Vitamin E depletion alone altered neither Lm nor DI. In tobacco-exposed animals
      in addition to vitamin E depletion, elastase-like activity, EIC in BAL fluid and
      DI were comparable to that in tobacco-exposed animals on a normal diet. However,
      Lm was markedly decreased with thickened epithelium and shrunk alveolar space.
      These results suggest that vitamin E depletion, when linked to tobacco exposure,
      might induce impaired lung development in the weanling rats, which is different
      from the emphysematous changes.

PMID- 7588447
TI  - Effect of acute administration of bleomycin on lung fluid balance in sheep.
AB  - This study examined the effects of acute administration of bleomycin (BLM) on
      lung liquid and protein exchange in anesthetized sheep prepared with caudal
      mediastinal lung lymph fistulas. Six sheep received BLM (15 U IV) after a
      baseline period, while seven others were given BLM after a steady state was
      obtained following elevation of left atrial pressure (PLA), a procedure intended
      to minimize changes in pulmonary microvascular surface area and produce high lung
      lymph flow (QL). Plasma and lung lymph angiotensin converting enzyme (ACE)
      activities were measured in order to independently assess the effects of BLM on
      pulmonary endothelial integrity. QL rose significantly in all animals following
      BLM. The ratio of lymph to plasma protein concentration (CL/CP) did not change in
      the group given BLM alone, and fell continuously during the period of PLA
      elevation after BLM in that group. Plasma and lung lymph ACE activities were
      unchanged following BLM administration in either group. The ultrastructure of the
      gas-exchanging region of lungs from animals in each group was examined by
      transmission electron microscopy. The data suggest that acute administration of a
      low dose of BLM does not increase pulmonary microvascular permeability, but may
      induce an increase in perfused pulmonary microvascular surface area responsible
      for increased QL.

PMID- 7588449
TI  - Association of ipsilateral head turning and dystonia in temporal lobe seizures.
AB  - We evaluated head turning in 239 complex partial seizures (CPS) with or without
      generalization in 32 patients with unilateral temporal lobe epilepsy (TLE). Head
      turns occurred in 187 seizures of 31 patients, more than once in 71 seizures. The
      first head turn was ipsilateral to the focus in 162 seizures (87%), with a mean
      latency of 22 s, as compared with 83 s for contralateral first head turns.
      Concomitant dystonic posturing of the arm occurred with 71% of all ipsilateral
      head turns and with 16% of all contralateral head turns. The mean difference in
      absolute latency between the first head turn and concomitant dystonic posturing
      was 6 s. Examination of all instances of concomitant head turning and dystonic
      posturing (160) showed them to be contralateral to each other in 154 (96%).
      Furthermore, the dystonia was contralateral and head turning was ipsilateral to
      the focus in 149 (93%). Forty-one seizures secondarily generalized, with
      transitional tonic head deviation contralateral to the focus in 35. Early head
      turning suggests an ipsilateral temporal seizures focus, particularly when
      associated with contralateral dystonic posturing. Similar mechanisms may account
      for both. Tonic head deviation preceding secondary generalization probably has a
      different mechanism.

PMID- 7588451
TI  - Complexity of focal spikes suggests relative epileptogenicity.
AB  - The EEGs of 39 children with focal or multifocal spikes were subjected to
      singular value decomposition (SVD) as provided by a commercial software program.
      We noted that in children with spikes but no clinical seizures the variance
      accounted for by the first component averaged 91.9%, whereas in children with
      seizures it was 68.0% (p < .001). The first component accounted for 85.4% in
      children with single spike foci, for 71.5% in those with multifocal spikes, and
      for 61.4% (p < 0.002) in those with both focal spikes and generalized spike-wave
      complexes. Spikes in the frontal and frontopolar areas were the most complex,
      suggesting that at least in children they tend to be the partial expression of a
      generalized seizure tendency rather than a result of strictly local pathology.

PMID- 7588450
TI  - Language before and after temporal lobectomy: specificity of acute changes and
      relation to early risk factors.
AB  - We evaluated language functions in 154 patients with left hemisphere speech
      dominance undergoing anterior temporal lobectomy (ATL). Measures of phonemic and
      semantic fluency, confrontation naming, repetition, comprehension, and reading
      were administered before and 3 weeks postoperatively. Patients were grouped by
      focus (left, LT; right, RT) and presence of early risk factors for development of
      seizures (ER, early risk, < or = 5 years; NER, no early risk): (LT-ER, n = 45; RT
      ER, n = 49; LT-NER, n = 27; RT-NER, n = 33). Preoperatively, the LT group showed
      a selective naming deficit as compared with the RT group. Postoperatively only
      the LT-NER group showed significant overall decline in language. For this group,
      the change was attributable to a selective decline in naming as compared with
      other functions. These data indicate that there is a specific risk to naming
      after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left
      hemisphere focus and the absence of an early risk factor for the development of
      seizures.

PMID- 7588452
TI  - Wavelength specificity of photoparoxysmal responses in idiopathic generalized
      epilepsy.
AB  - Using optic filters, we analyzed the wave-length specificity of photoparoxysmal
      responses (PPR) in photosensitive patients with idiopathic generalized epilepsy
      (IGE). We specified the wavelength spectrum approximately 700 nm (660-720 nm) as
      the only visible spectrum essential for eliciting PPR in some normal trichromat
      IGE patients and showed that any flashing lights containing this essential
      wavelength spectrum could elicit PPR independent of the number of stimulated
      cones. Absorption of the wavelength spectrum approximately 700 nm by optic
      filters eliminated PPR in normal trichromat IGE patients. In an IGE patient with
      deuteranomaly, intermittent flashing lights containing a part of the wavelength
      spectrum from 580 to 700 nm elicited PPR. These data suggest a new interpretation
      of wavelength specificity of PPR: Flashing lights containing the wavelength
      spectrum that does not produce antagonistic cone interactions at the level of
      retinal ganglion cells can elicit PPR in some photosensitive IGE patients.

PMID- 7588459
TI  - It is not harmful for patients with epilepsy to view their own seizures.
AB  - Having a seizure in public is a concern to people with epilepsy and can represent
      a barrier to psychosocial adjustment. Seeing his or her own seizures might help
      the patient deal with seizures more realistically, but also could be emotionally
      detrimental. We therefore showed patients videos of their own seizures before
      their discharge from our inpatient epilepsy monitoring unit. One of the
      investigators was present to answer questions. The Spielberger State Trait
      Anxiety Scale (SSTAS) was administered before and after viewing and 1 month later
      together with a questionnaire related to the patients' feelings and attitudes
      about viewing their own seizures. Results using one-way repeated-measures
      multivariate analysis of variance (MANOVA) showed no differences for the items in
      the pre- and posttest questionnaire. For the SSTAS, no significant differences
      were detected among the pretest and the two posttests by one-way repeated ANOVA
      (p = 0.10). These results suggest that it is not harmful to view one's own
      seizures in a controlled setting.

PMID- 7588457
TI  - Psychogenic elaboration of simple partial seizures.
AB  - Seizures that cause loss of consciousness (LOC) can be classified as epileptic or
      nonepileptic based on evaluation of ictal semiology and analysis of changes in
      EEG events, recorded with continuous scalp EEG and video monitoring. We report 3
      patients who had hippocampal electrographic seizures documented with intracranial
      EEG recording with no accompanying scalp EEG change immediately preceding
      psychogenic unresponsiveness. Each patient also had complex partial seizures
      (CPS) originating in the hippocampus. Some individuals can have complex
      interactions of epileptic and nonepileptic seizures.

PMID- 7588453
TI  - Development of the quality of life in epilepsy inventory.
AB  - We developed an instrument to measure health-related quality of life (HRQOL) in
      epilepsy. A 99-item inventory was constructed from the RAND 36-Item Health Survey
      (generic core), with 9 additional generic items, 48 epilepsy-targeted items, and
      6 other items concerning attitudes toward epilepsy and self-esteem. We
      administered the 99-item inventory to 304 adults with epilepsy at 25 epilepsy
      centers. Patients and patient-designated proxies completed the inventory and were
      retested 1-91 days later. A multitrait scaling analysis of these data led to
      retention of 86 items distributed in 17 multiitem scales (Cronbach's alpha ranged
      from 0.78 to 0.92). Factor analysis of the 17 multiitem scales yielded four
      underlying dimensions of health: an epilepsy-targeted dimension, a cognitive
      factor, mental health, and physical health. Construct validity was supported by
      significant patient-proxy correlations for all scales and correlations between
      neuropsychologic tests and self-reported emotional and cognitive function (all p
      values < 0.05). There were significant negative correlations between the four
      factor scores derived from the HRQOL scales and neurotoxicity, systemic toxicity,
      and health care utilization (except for the correlation between mental health
      factor and health care utilization; all p values < 0.05). Patients who were
      seizure-free in the preceding year reported better HRQOL for the overall score,
      three of the four factor scores, and 8 of the 17 scale scores than did patients
      with a high frequency of seizures. Relative validity analysis showed that the
      epilepsy-targeted factor and three of its four component scales were more
      sensitive to categorization of patients by severity of seizure frequency and type
      than scales tapping physical health, mental health, or cognitive function. These
      cross-sectional data support the reliability and validity of this measure of
      HRQOL in epilepsy. The addition of an epilepsy-targeted supplement to the generic
      core improved the sensitivity to severity of epilepsy. The 86 items included in
      the field testing were supplemented by three additional items to form the Quality
      of Life in Epilepsy (QOLIE-89) inventory.

PMID- 7588454
TI  - Felbamate monotherapy: implications for antiepileptic drug development.
AB  - We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients
      with partial and secondarily generalized seizures undergoing presurgical
      monitoring at a single site. The study design was a double-blind placebo
      controlled parallel monotherapy trial. Forty patients whose seizures had not been
      controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type
      was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and
      patients were drug-free for 5.3 +/- 2.4 days before randomization to FBM or
      placebo. After a 4-day titration, seizures were counted for 14 days. Patients
      receiving FBM had significantly lower seizure rates, whether all randomized
      patients, patients who survived titration, or study completers were compared.
      Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21
      receiving FBM, completed the 18-day study. Two FBM patients dropped out due to
      seizures, and 6 dropped out due to side effects, including anxiety, difficulty
      sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten
      placebo patients met the criteria for premature discontinuation owing to
      seizures, and 1 hd an episode of panic. There was no evidence of hepatic or
      hematologic toxicity. FBM reduces seizure frequency in patients with localization
      related epilepsy.

PMID- 7588458
TI  - Outcome after diagnosis of psychogenic nonepileptic seizures.
AB  - Information regarding outcome in patients with psychogenic nonepileptic seizures
      (PNES) is limited. We attempted to contact 72 consecutive patients with PNES
      confirmed by video-EEG monitoring: 51 of 72 (71%) were reached a mean of 15
      months (range 12-27 months) after diagnosis and agreed to answer a structured
      telephone questionnaire. The questionnaire assessed the number of PNES in the
      last 6 months, antiepileptic drug (AED) use, occupational status, global self
      rating, and extent of psychotherapeutic treatments. PNES had ceased in 18 of 51
      (35%), decreased > 80% in 21 of 51 (41%), and decreased < 80% in 12 of 51 (24%).
      Thirty-three of 51 (65%) were not taking AEDs. Occupational status improved in
      20% and did not change in 75%. Overall, 29 of 51 (57%) rated themselves markedly
      improved and 15 of 51 (29%) rated themselves unchanged or worse. Persisting PNES
      were associated with longer duration of PNES before diagnosis (p < 0.02) and
      presence of additional psychiatric disease (p < 0.01). Persisting PNES were not
      associated with gender, presence of epileptic seizures, or extent of
      psychotherapeutic treatments after diagnosis. Placebo saline infusion had been
      administered in some patients to help precipitate PNES. This did not affect the
      number of psychotherapy visits or outcome. We conclude that PNES cease or
      significantly decrease in most patients, but occupational status does not improve
      as often. Earlier diagnosis may improve outcome.

PMID- 7588460
TI  - Cingulate kindling in Senegalese baboons, Papio papio.
AB  - Kindling of the cingulate cortex in the Senegalese baboon Papio papio led to a
      protracted nonconvulsive seizure state characterized by immobile staring with
      (anterior cingulate, AC) or without (posterior cingulate, PC) widening of eyelids
      and neck flexion, followed by postictal visual searching behavior. Despite early
      bilateral spread of EEG discharges, ictal and interictal patterns remained
      persistently asymmetric. Secondary generalization was rapid and predictable once
      contralateral lower facial twitching associated with sustained adversion
      developed. After the primary site had been kindled, stimulation of the
      contralateral homotopic posterior cingulate cortex readily produced
      afterdischarge. However, it remained localized and kindling growth did not occur.
      The findings suggest that (a) the cingulate cortex can support nonconvulsive
      seizures; (b) cingulate seizures are accompanied by asymmetric convexity EEG
      discharges indicating its lateralized onset; (c) further evolution to convulsive
      seizures after kindling of cingulate cortex requires access to the ipsilateral
      frontocentral cortex responsible for facial twitching; and (d) the development of
      focal epileptogenesis at one cingulate site interferes with clinical seizure
      development at the homotopic contralateral site.

PMID- 7588463
TI  - Oculogyric crisis induced by carbamazepine.
AB  - A 32-year-old man with mental retardation and uncontrolled complex partial
      epilepsy receiving carbamazepine (CBZ) and divalproex sodium (VPA), developed
      frequent episodes of forced upward gaze after increase in the daily VPA dosage.
      CBZ dosage was decreased, with prompt resolution of symptoms. The upward gaze
      problem recurred several months later. CBZ dosage was decreased further with
      subsequent resolution of symptoms. Therefore, the oculogyric crisis (OGC)
      appeared to be induced by CBZ.

PMID- 7588462
TI  - Discordant occurrence of cerebral unilateral heterotopia and epilepsy in
      monozygotic twins.
AB  - Cerebral developmental malformations are increasingly recognized as a cause of
      epilepsy. Magnetic resonance imaging (MRI) has advanced our understanding of
      these disorders and their relation to epilepsy. We report the occurrence of
      discordant unilateral heterotopia and epilepsy in monozygotic twins. The affected
      individual developed intractable focal seizures at age 16 years. Mild cognitive
      difficulties had been present in early life. Evaluation showed right hemisphere
      EEG epileptogenic abnormalities, and the MRI scan showed massive right hemisphere
      heterotopia. EEG and MRI examinations in the patient's twin brother were normal.
      These findings suggest that the development of some developmental brain
      malformations and epilepsy is strongly influenced by nongenetic factors such as
      an environmental insult.

PMID- 7588461
TI  - Near-patient rapid assay of phenytoin concentration.
AB  - The Biotrack 516 is a simple, automated whole blood phenytoin (PHT) assay that
      reports corresponding total serum concentrations in 3 min. We compared Biotrack
      results in 58 patients with the total and unbound serum PHT concentrations
      measured by the standard TDx fluorescence polarization immunoassay. Correlation
      with total TDx concentration was high (r = 0.98); median absolute error was 1.4
      micrograms/ml. Correlation of unbound PHT with Biotrack (r = 0.95) was comparable
      to correlation of unbound and total TDx (r = 0.94). The Biotrack assay is a
      promising method for clinical monitoring of PHT concentrations.

PMID- 7588456
TI  - Thyroid status of patients receiving long-term anticonvulsant therapy assessed by
      peripheral parameters: a placebo-controlled thyroxine therapy trial.
AB  - Thyroid hormone concentrations and measures reflecting thyroid function were
      studied in sera from 35 patients receiving long-term phenytoin (PHT) or
      carbamazepine (CBZ) therapy. The mean concentrations of T4, FT4, FT3, and rT3,
      but not T3, of these patients were significantly lower than those of 19 controls
      of similar age and sex distribution. The mean serum thyrotropin (TSH)
      concentration was slightly but significantly higher in patients than in controls,
      but the serum TSH response to TRH was not significantly increased. In patients,
      the higher mean clinical diagnostic index of hypothyroidism (CDI-HT: -20.3 +/-
      19.1 vs. -33.7 +/- 8.5, p < 0.05) and higher ratio of preejection period to left
      ventricular ejection time (PEP/LVET: 0.343 +/- 0.065 vs. 0.334 +/- 0.030, p <
      0.05) than in controls were compatible with tissue hypothyroidism. However,
      comparison of the mean levels of alanine aminotransferase (ALAT), creatine kinase
      (CK), creatinine, triglycerides, cholesterol, high-density lipoprotein (HDL)
      cholesterol, osteocalcin, procollagen type III aminoterminal propeptide, and
      somatomedin-C showed no significant differences between patients and controls.
      The increased mean angiotensin convertase and sex hormone-binding globulin (SHBG)
      levels, typical of hyperthyroidism, were probably caused by drug effects.
      Fourteen patients with a subnormal FT4 concentration in serum participated in a
      double-blind thyroxine treatment cross-over study. Neither the mean CDI-HT score,
      nor the systolic time intervals were significantly different between the
      thyroxine and placebo periods. Five patients benefited subjectively from the
      treatment. On the basis of all data from the cross-sectional and thyroxine
      treatment studies, we conclude that patients receiving anticonvulsant drugs
      chronically are eumetabolic and do not need thyroxine supplementation.

PMID- 7588455
TI  - Dose frequency and dose interval compliance with multiple antiepileptic
      medications during a controlled clinical trial.
AB  - Compliance with medication regimens and clinical trial schedules was evaluated
      during a study of vigabatrin (VGB), an antiepileptic drug (AED). Medication Event
      Monitors (MEMS, Aprex Corp., Fremont, CA, U.S.A.) were provided to monitor use of
      VGB and other AEDs administered to 111 patients at 10 sites. MEMS reports showed
      the number of doses administered daily, times of doses, and intervals between
      doses. The 66 patients whose data were evaluable took VGB as prescribed (twice
      daily, b.i.d.) on 89 +/- 7% of days in the clinical trial (mean 189 +/- 63 days).
      However, only 66 +/- 24% of doses were taken within the 9-15-h dose interval
      window for twice-daily dosing, a lower rate than that for dose frequency
      compliance (p < 0.001). Concomitant medications prescribed b.i.d. (n = 66) (86 +/
      11% dose frequency compliance) were taken at lower rates than VGB (p < 0.02).
      Interval compliance also was lower for concomitant b.i.d. medications (59 +/-
      26%) than for VGB (p < 0.01). Dose frequency compliance for thrice-daily (t.i.d.)
      medications (n = 36) was 80 +/- 18 and 40 +/- 19% for interval compliance (6-10
      h) (both p < 0.0001 vs. VGB). Dose frequency compliance for four times daily
      (q.i.d.) medications (n = 23) was 80 +/- 23 and 33 +/- 18% for interval
      compliance (4-8 h) (both p < 0.0001 vs. VGB). Patients at eight sites did not use
      MEMS properly, often for practical reasons, voiding including of data for 93
      medications (32%) because of noncompliance with the study design to monitor
      compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588465
TI  - Language mapping in epilepsy patients undergoing dominant hemisphere anterior
      temporal lobectomy.

PMID- 7588464
TI  - Ictal HMPAO-single photon emission computed tomography findings in reading
      epilepsy in a Japanese boy.
AB  - Reading epilepsy is rare. We report a 14-year-old right-handed Japanese boy who
      had had jaw jerking only while reading since age 12 years. The episodes occurred
      every time he read an English textbook and sometimes during prolonged reading of
      a Japanese textbook. The jaw jerking evolved to generalized tonic-clonic seizures
      (GTCS) on only two occasions during prolonged reading aloud. Routine EEGs showed
      no abnormality. After a few minutes of reading, however, the EEG showed bilateral
      2-Hz, 150-microV spike-wave complexes with left frontotemporal accentuation,
      accompanied by jaw jerking. Ictal single photon emission computed tomography
      (SPECT) with [99Tc]hexamethylpropylene amine oxime (HMPAO) showed focal
      hyperperfusion of the frontal lobes bilaterally and of the left temporal area.
      Interictal SPECT and magnetic resonance imaging (MRI) were normal. The
      combination of valproate (VPA) and clonazepam (CZP) almost eliminated his
      symptoms. Ictal SPECT is a useful technique for seizure localization in reading
      epilepsy.

PMID- 7588466
TI  - Quantum leaps in technology transfer.

PMID- 7588467
TI  - What does decreased funding for science mean to the United States?

PMID- 7588469
TI  - Nuclear waste: a cancer cure?

PMID- 7588468
TI  - Malaria control in Zambia and southern Africa.

PMID- 7588473
TI  - Environmental science in the city that never sleeps.

PMID- 7588470
TI  - Hints on hantavirus.

PMID- 7588472
TI  - Prostate gene isolated.

PMID- 7588471
TI  - CDC says NC workers get little legal protection from smoke.

PMID- 7588474
TI  - The impact of ozone.

PMID- 7588475
TI  - MTBE: the headache of cleaner air.

PMID- 7588476
TI  - A national proposition?

PMID- 7588477
TI  - Predicting the path of pollutants.

PMID- 7588478
TI  - The carcinogenesis bioassay in perspective: application in identifying human
      cancer hazards.
AB  - The selection process for chemicals tested in the rodent carcinogenicity bioassay
      has been biased toward chemicals suspected of potential carcinogenicity. Results
      from carcinogenicity bioassays of 400 chemicals tested by the National Cancer
      Institute/National Toxicology Program (NCI/NTP) were analyzed to determine the
      dependence of positive results on chemical selection criteria: those suspected of
      being carcinogenic and those selected based on large volumes produced and
      widespread exposures. Of these chemicals, 210 (52%) induced carcinogenicity in at
      least one organ of one sex of one species of the four sex/species groups
      typically used by NCI/NTP. Only 92 of the 400 chemicals (23%) were positive in
      two species and thus by international criteria are considered likely to pose a
      carcinogenic hazard to humans. A total of 267 chemicals (67%) were selected as
      suspect carcinogens, and 187 (68%) of these were carcinogenic. Suspect chemicals
      account for 86% of chemicals with at least one positive result and account for
      90% of chemicals considered positive in two species. The International Agency for
      Research on Cancer (IARC) lists only 5 of the 400 chemicals as carcinogenic to
      humans (group 1) and 10 as probably carcinogenic to humans (group 2A). The
      majority (80%) of the 133 chemicals selected only on production/exposure
      considerations were not carcinogenic in animals, even when tested at the maximum
      tolerated (or minimally toxic) dose. Only 9 (6.8%) were positive in two species,
      and none is listed in IARC groups 1 or 2A. Thus, on the basis of our analyses we
      predict that less than 5-10% of the 75,000 chemicals in commercial use might be
      reasonably anticipated to be carcinogenic to humans.

PMID- 7588479
TI  - Risk and revisionism in arsenic cancer risk assessment.
AB  - Oral exposures of nonoccupational populations to environmental inorganic arsenic
      are associated with skin and internal cancers as well as various noncarcinogenic
      effects. Cancer risk assessments have been based largely on epidemiological
      studies of a large population exposed to inorganic arsenic in well water in
      Taiwan. Criticisms and skepticism of the use of the Taiwanese data for estimating
      arsenic cancer risks outside of Taiwan, including potential use by the U.S.
      Environmental Protection Agency for regulatory purposes, have been expressed on
      various grounds. The nature and extent of such criticisms have sharpened with
      recent findings in the exposed Taiwanese of increased incidence of internal
      cancers (bladder, kidney, liver, and lung), in addition to already-observed skin
      cancer, coupled with a good likelihood that these findings will produce more
      stringent arsenic regulation in the United States and elsewhere. These criticisms
      collectively posit a revisionist view that: 1) cancer incidence among the
      Taiwanese was amplified by a number of host and environmental factors not
      applicable elsewhere, 2) the cancer dose-response curve may not be linear at the
      lower exposures elsewhere, and 3) there is a toxicokinetic and metabolic
      threshold to cancer risk that was exceeded by the Taiwanese. However, a number of
      the arguments against wide use of the Taiwanese data are flawed and subject to
      challenge. We explore some of these arguments and their critical evaluation,
      particularly as they concern certain exposure, metabolic, and nutritional
      determinants of the cancer risk of inorganic arsenic in the Taiwanese.

PMID- 7588481
TI  - Promotion of hepatic preneoplastic lesions in male B6C3F1 mice by unleaded
      gasoline.
AB  - In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor
      promoter and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen
      in male mice. However, UG vapor had similar transient mitogenic effects in
      nonlesioned liver of both male and female mice under the conditions of the cancer
      bioassay. We used an initiation-promotion protocol to determine whether UG vapor
      acts as a liver tumor promoter in male mice and to examine proliferative effects
      that may be critical to tumor development. Twelve-day-old male B6C3F1 mice were
      injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle.
      Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5
      days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a
      significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN
      initiated mice, whereas no macroscopic masses were observed in non-initiated
      mice. Altered hepatic foci (AHF), which were predominantly basophilic in
      phenotype, were found almost exclusively in DEN-initiated mice. UG treatment
      significantly increased both the mean volume (threefold) and the volume fraction
      (twofold) of the AHF without increasing the number of AHF per unit area. UG also
      induced hepatic pentoxyresorufin-O-dealkylase (PROD) activity, a marker of CYP2B,
      by more than 12-fold over control with or without DEN cotreatment. To study
      hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2'
      deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured
      hepatocyte BrdU labeling index (LI) in AHF and nonlesioned liver.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7588484
TI  - Do waste incinerators induce adverse respiratory effects? An air quality and
      epidemiological study of six communities.
AB  - The purpose of the study presented here was to simultaneously measure air quality
      and respiratory function and symptoms in populations living in the neighborhood
      of waste incinerators and to estimate the contribution of incinerator emissions
      to the particulate air mass in these neighborhoods. We studied the residents of
      three communities having, respectively, a biomedical and a municipal incinerator,
      and a liquid hazardous waste-burning industrial furnace. We compared results with
      three matched-comparison communities. We did not detect differences in
      concentrations of particulate matter among any of the three pairs of study
      communities. Average fine particulate (PM2.5) concentrations measured for 35 days
      varied across study communities from 16 to 32 micrograms/m3. Within the same
      community, daily concentrations of fine particulates varied by as much as
      eightfold, from 10 to 80 micrograms/m3, and were nearly identical within each
      pair of communities. Direct measurements of air quality and estimates based on a
      chemical mass balance receptor model showed that incinerator emissions did not
      have a major or even a modest impact on routinely monitored air pollutants. A
      onetime baseline descriptive survey (n = 6963) did not reveal consistent
      community differences in the prevalence of chronic or acute respiratory symptoms
      between incinerator and comparison communities, nor did we see a difference in
      baseline lung function tests or in the average peak expiratory flow rate measured
      over a period of 35 days. Based on this analysis of the first year of our study,
      we conclude that we have no evidence to reject the null hypothesis of no acute or
      chronic respiratory effects associated with residence in any of the three
      incinerator communities.

PMID- 7588482
TI  - Using three-dimensional quantitative structure-activity relationships to examine
      estrogen receptor binding affinities of polychlorinated hydroxybiphenyls.
AB  - Certain phenyl-substituted hydrocarbons of environmental concern have the
      potential to disrupt the endocrine system of animals, apparently in association
      with their estrogenic properties. Competition with natural estrogens for the
      estrogen receptor is a possible mechanism by which such effects could occur. We
      used comparative molecular field analysis (CoMFA), a three-dimensional
      quantitative structure-activity relationship (QSAR) paradigm, to examine the
      underlying structural properties of ortho-chlorinated hydroxybiphenyl analogs
      known to bind to the estrogen receptor. The cross-validated and conventional
      statistical results indicate a high degree of internal predictability for the
      molecules included in the training data set. In addition to the phenolic (A) ring
      system, conformational restriction of the overall structure appears to play an
      important role in estrogen receptor binding affinity. Hydrophobic character as
      assessed using hydropathic interaction fields also contributes in a positive way
      to binding affinity. The CoMFA-derived QSARs may be useful in examining the
      estrogenic activity of a wider range of phenyl-substituted hydrocarbons of
      environmental concern.

PMID- 7588480
TI  - Protracted neurotoxicity from chlordane sprayed to kill termites.
AB  - Over 250 adults and children were exposed to chlordane when the wooden building
      surfaces and soil around an apartment complex were sprayed in 1987. Two hundred
      sixteen adults had neurobehavioral functions measured and completed
      questionnaires for symptom frequency, mood status, confounding factors, and
      medical, rheumatic, and respiratory disorders in 1994. Measurements included
      simple and choice reaction time, balance, blink reflex latency, color vision,
      cognitive, perceptual motor, memory, and recall functions. We analyzed 216
      exposed and 174 referent adults. Age, educational level, weight, height, and
      gender ratio were similar for the exposed and referent groups. Performance of
      balance, reaction times, Culture Fair, digit symbol, verbal recall, and trail
      making were significantly impaired in exposed persons compared to referents. Mood
      state scores were elevated, as were the frequencies of respiratory,
      neurobehavioral, and rheumatic symptoms. In contrast, long-term memory function
      was similar in both groups, consistent with its status before exposure. There was
      no identified bias or confounding factors. Chlordane exposure was associated with
      protracted impairment of neurophysiological and psychological functions. The
      central nervous system is the most important target of chlorinated cyclodiene
      insecticides. Human exposure should be prohibited.

PMID- 7588485
TI  - A pharmacokinetic model of inhaled methanol in humans and comparison to methanol
      disposition in mice and rats.
AB  - We estimated kinetic parameters associated with methanol disposition in humans
      from data reported in the literature. Michaelis-Menten elimination parameters
      (Vmax = 115 mg/L/hr; Km = 460 mg/L) were selected for input into a semi
      physiologic pharmacokinetic model. We used reported literature values for blood
      or urine methanol concentrations in humans and nonhuman primates after methanol
      inhalation as input to an inhalation disposition model that evaluated the
      absorption of methanol, expressed as the fraction of inhaled methanol
      concentration that was absorbed (phi). Values of phi for nonexercising subjects
      typically varied between 0.64 and 0.75; 0.80 was observed to be a reasonable
      upper boundary for fractional absorption. Absorption efficiency in exercising
      subjects was lower than that in resting individuals. Incorporation of the kinetic
      parameters and phi into a pharmacokinetic model of human exposure to methanol,
      compared to a similar analysis in rodents, indicated that following an 8-hr
      exposure to 5000 ppm of methanol vapor, blood methanol concentrations in the
      mouse would be 13- to 18-fold higher than in humans exposed to the same methanol
      vapor concentration; blood methanol concentrations in the rat under similar
      conditions would be 5-fold higher than in humans. These results demonstrate the
      importance in the risk assessment for methanol of basing extrapolations from
      rodents to humans on actual blood concentrations rather than on methanol vapor
      exposure concentrations.

PMID- 7588483
TI  - Xenoestrogens alter mammary gland differentiation and cell proliferation in the
      rat.
AB  - We investigated mammary gland differentiation and cell proliferation in rats
      after acute exposure to xenoestrogens. Pubertal female Sprague-Dawley rats
      (six/group) were treated for 1 week with diethylstilbestrol (DES), genistein,
      o,p'-DDT, Aroclor 1221, Aroclor 1254, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      or the vehicle, sesame oil. Animals were killed 18 hr after the last treatment.
      Analysis of mammary whole-mounts revealed that exposure to DES, genistein, and
      o,p'-DDT resulted in enhanced gland differentiation and increased epithelial cell
      proliferation as measured by proliferating cell nuclear antigen
      immunohistochemistry, TCDD treatment inhibited cell proliferation and gland
      development. Aroclor 1221 and Aroclor 1254 treatments had slight but not
      statistically significant effects on cell proliferation and mammary gland
      development. We conclude that DES, genistein, and o,p'-DDT given to pubertal rats
      act as morphogens; i.e., they increase cell proliferation, which promotes
      maturation of the undifferentiated terminal end buds to more differentiated
      lobular terminal ductal structures.

PMID- 7588486
TI  - Metabolism of meso-2,3-dimercaptosuccinic acid in lead-poisoned children and
      normal adults.
AB  - Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent
      for heavy-metal poisoning. While studying the urinary elimination of unaltered
      DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead
      poisoning, we observed a pattern of urinary drug elimination after meals
      suggestive of enterohepatic circulation. The excretion of lead in urine patterned
      the elimination of altered DMSA rather than the parent molecule. In addition, the
      half-life of elimination of DMSA via the kidney was positively associated with
      blood lead concentration. Two additional crossover studies of DMSA kinetics were
      conducted in normal adults to confirm the presence of enterohepatic circulation
      of DMSA after meals. In one, increases in plasma total DMSA concentration were
      observed after meals in all six subjects; these increases were prevented by
      cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the
      administration of neomycin also prevented increases in DMSA after meals. These
      studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic
      circulation and that microflora are required for DMSA reentry; 2) in children,
      moderate lead exposure impairs renal tubular drug elimination; and 3) a
      metabolite of DMSA appears to be an active chelator.

PMID- 7588487
TI  - Assessment of dietary exposure to trace metals in Baffin Inuit food.
AB  - Chronic metal toxicity is a concern in the Canadian Arctic because of the
      findings of high metal levels in wildlife animals and the fact that traditional
      food constitutes a major component of the diet of indigenous peoples. We examined
      exposure to trace metals through traditional food resources for Inuit living in
      the community of Qikiqtarjuaq on Baffin Island in the eastern Arctic. Mercury,
      cadmium, and lead were determined in local food resources as normally prepared
      and eaten. Elevated concentrations of mercury ( > 50 micrograms/100 g) were found
      in ringed seal liver, narwhal mattak, beluga meat, and beluga mattak, and
      relatively high concentrations of cadmium and lead ( > 100 micrograms/100 g) were
      found in ringed seal liver, mussels, and kelp. Quantified dietary recalls taken
      seasonally reflected normal consumption patterns of these food resources by adult
      men and women ( > 20 years old) and children (3-12 years old). Based on
      traditional food consumption, the average daily intake levels of total mercury
      for both adults (65 micrograms for women and 97 micrograms for men) and children
      (38 micrograms) were higher than the Canadian average value (16 micrograms). The
      average weekly intake of mercury for all age groups exceeded the intake
      guidelines (5.0 micrograms/kg/day) established by the Joint Food and Agriculture
      Organization/World Health Organization Expert Committee on Food Additives and
      Contaminants. The primary foods that contributed to metal intake for the Baffin
      Inuit were ringed seal meat, caribou meat, and kelp. We review the superior
      nutritional benefits and potential health risks of traditional food items and
      implications for monitoring metal contents of food, clinical symptoms, and food
      use.

PMID- 7588488
TI  - Conditional switching: a new variety of regression with many potential
      environmental applications.
AB  - We introduce a new form of regression that has many applications to environmental
      studies. For a sequence composed of key variates with prototypic value chi, this
      form differs from the estimation of a location parameter-based curve, mu(chi), a
      scale parameter-based curve, sigma(chi), or other currently used types of
      regression. Instead of estimating a curve location, scale, or alpha-quantile
      parameter, it assumes that there are two or more population subgroups; for
      example, consisting of unsensitized and sensitized individuals, respectively.
      Although within each subgroup the relationships mu(chi) or sigma(chi) may or may
      not be horizontal, these relationships are not deemed to be of primary
      importance. Instead, the mixing parameter P that indexes the proportions of the
      two subgroups is treated as being related to the key variate value chi. In the
      sense that its goal is the estimation of a proportion, the new procedure
      resembles logit regression. But, in terms of the continuous spectrum of values
      attained by the response variate, the means used to attain its goal are
      dissimilar from those of logit regression. Specifically, group membership is not
      known directly but is determined from a proxy continuous variate whose values
      overlap between groups. Examples are given with simulated and natural data where
      this new form of regression is applied. We believe that conditional switching
      regression is a particularly valuable research tool when chemical level chi of an
      induced asthma attack or birthweight chi measured in a study of the biomarker
      cotinine's effect on pregnancy outcomes determines whether an attack or a
      negative outcome occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588493
TI  - Low birth weight and preterm births among infants born to women living near a
      municipal solid waste landfill site in Montreal, Quebec.
AB  - Using data from the Quebec birth registration file, case-control analyses were
      conducted in order to evaluate the risk of low birth weight (< 2500 g), very low
      birth weight (< 1500 g), preterm birth (< 37 completed weeks), and small for
      gestational age (< third percentile) among infants born to women living near a
      municipal solid waste landfill site in a densely populated area of Montreal,
      Quebec. Potential exposure to vapors and gases (biogas) was defined in terms of
      exposure zones around the site. A set of reference areas was selected to be
      similar to these exposure zones on a number of key sociodemographic factors. Odds
      ratios (OR) adjusted for variables on the birth file were calculated using
      logistic regression. Low birth weight was significantly elevated in the exposure
      zone proximal to the site (adjusted OR = 1.20; 1107 exposed cases; 95% confidence
      interval: 1.04-1.39). Excess risks were also observed for small for gestational
      age, but the association was not as strong as for low birth weight (adjusted OR =
      1.09; 951 exposed cases; 95% confidence interval: 0.96-1.24). No significant
      positive associations were observed for very low birth weight or for preterm
      birth. Because it was not possible to evaluate the effects of all potentially
      important confounding factors and because detailed environmental exposure
      assessments were not available, it is not possible to conclude definitively
      whether low birth weight and small for gestational age are associated with
      exposure to biogas. Further studies at this and at other landfill sites are
      warranted in order to confirm or refute these observations and to investigate
      other possible adverse reproductive outcomes.

PMID- 7588495
TI  - Chemotaxis of alveolar macrophages and neutrophils in response to microbial
      products derived from organic dust.
AB  - The inhalation of organic dust has been implicated to cause a large number of
      occupational lung diseases. A common event in these diseases is an inflammatory
      reaction affecting airway and alveolar tissue that is characterized by the
      recruitment of different types of inflammatory cells. Mechanisms of chemotaxis of
      alveolar macrophages (AMs) and neutrophils (PMNs) in response to microbial
      products derived from organic dust were studied. Seven agents known to be
      etiological agents causing respiratory symptoms (extract and endotoxin of
      Enterobacter agglomerans, extracts from Thermoactinomyces vulgaris and
      Aspergillus fumigatus, thermophilic protease, and two preparations of glucans)
      were used for experiments. These agents were evaluated for their ability to
      directly attract AMs and PMNs and to stimulate alveolar macrophages to release
      chemotactic factors for other AMs and PMNs. The microbial products were able to
      attract both AMs and PMNs directly in a dose-dependent manner and the exposure of
      cultured AMs to most agents were stimulatory for production of chemotactic
      activity for AMs and PMNs. The generation and release of this activity by AMs may
      provide a mechanism for the initiation and amplification of inflammatory
      reactions in the lung after inhalation of organic dust. Results of these in vitro
      studies may be relevant to the pathogenesis of alveolitis in organic dust-induced
      lung diseases.

PMID- 7588489
TI  - Baculovirus and insect cell gene expression: review of baculovirus biotechnology.
AB  - The BEVS continues to evolve as a powerful, flexible tool for molecular biology,
      protein function, and biomedical research. Future developments offer the promise
      of replacement of hazardous chemical insecticides with environmentally safe
      biopesticides, construction of baculovirus vectors which encode genes for
      specific post-translational modifications, and establishment of efficient, stably
      transformed insect cell lines. FDA approval of BEVS-produced products offer the
      prospect of new biopharmaceuticals, in particular human therapeutics and
      vaccines, to improve human health and increase the quality of life for millions
      of people.

PMID- 7588491
TI  - Race, class, and environmental health: a review and systematization of the
      literature.
AB  - This paper analyzes and systematizes the race and class differentials in exposure
      to toxic hazards and actual health outcomes. Research is categorized into the
      following: Proximity to known hazards includes (1) presence of hazardous waste
      sites and facilities (landfills, incinerators, Superfund sites), (2) exposure to
      air pollution, (3) exposure to various environmental hazards, e.g., toxic
      releases and hazards in pesticides and foods; Regulation, amelioration and
      cleanup includes (4) record of decisions (RODs) and cleanups at NPL sites, (5)
      regulatory action, as measured by assessed fines for environmental pollution;
      Health effects includes (6) specific health outcomes which are related to
      environmental burden (e.g., blood lead levels). Proximity to prospective hazards
      includes (7) sitting decisions for incinerators, hazardous waste sites, and
      nuclear storage sites. The overwhelming bulk of evidence supports the
      "environmental justice" belief that environmental hazards are inequitably
      distributed by class, and especially race.

PMID- 7588496
TI  - Environmental contamination by cobalt in the vicinity of a cemented tungsten
      carbide tool grinding plant.
AB  - Surface soil and dust samples have been collected from the vicinity of a hard
      metal (cemented tungsten carbide) tool grinding factory. As a result of poor
      waste management practices, dusts generated by the grinding operation were, for
      the most part, swept from the interior of the building onto open ground at the
      rear of the plant. The potential for contamination of the local environment with
      cobalt, tungsten, and other metals as a result of dust being either resuspended
      from the resulting uncontrolled mound of debris or emitted from the factory vents
      was considerable. Levels of cobalt in local soils were found to be as high as
      12,700 mg kg-1; almost 2000 times higher than the average value for in the United
      States. Scanning electron microscopy and energy dispersive X-ray micro-analysis
      examination of the waste dust particles revealed that the individual particles
      were, in general, composites containing variable quantities of tungsten, cobalt,
      calcium, titanium, and iron. Individual particles in soil samples collected at
      some distance from the plant were less heterogeneous, and fewer particles
      contained detectable quantities of cobalt. This would suggest that a degree of
      disassociation had occurred in the soil environment resulting in a mobilization
      of the cobalt.

PMID- 7588494
TI  - Chronic lead treatment accelerates photochemically induced platelet aggregation
      in cerebral microvessels of mice, in vivo.
AB  - Effects of two chronic treatment levels with lead on platelet aggregation in
      cerebral (pial) microcirculation of the mouse were investigated. Exposure to lead
      was made by subcutaneous injections for 7 days of lead acetate dissolved in 5%
      glucose solution, vehicle. Two doses of lead were used, a low dose of 0.1 mg/kg
      and a high dose of 1.0 mg/kg. Adult male mice were divided into three groups, 10
      each; one group was injected with vehicle (control), another was injected with
      the low dose, and the third was injected with the high dose. Additional mice were
      used for the determination of hematological parameters and for the lead level in
      serum of the three groups. On the eighth day, platelet aggregation in pial
      microvessels of these groups of mice was carried out in vivo. Animals were
      anesthetized (urethane, 1-2 mg/g, ip), the trachea was intubated, and a
      craniotomy was performed. Platelet aggregation in pial microvessels was induced
      photochemically, by activation of circulating sodium fluorescein (0.1 mg/25 g,
      iv) with an intense mercury light. The time required for the first platelet
      aggregate to appear in pial arterioles was significantly shorter in the lead
      treated mice than in control. This effect was in a dose-dependent manner; 113 +/-
      44 sec for low dose and 71 +/- 18 sec for high dose vs 155 +/- 25 sec for
      control, P < 0.02 and P < 0.001, respectively. Between the two lead-treated
      groups, the high dose significantly (P < 0.05) shortened the time to first
      aggregate. These data evidenced an increased susceptibility to cerebrovascular
      thrombosis as a result of exposure to lead.

PMID- 7588492
TI  - Short-term effects of air pollution on hospital emergency outpatient visits and
      admissions in the greater Athens, Greece area.
AB  - The short-term effects of air pollution on morbidity in the Athens population
      were studied. Data were collected on the daily number of emergency outpatient
      visits and admissions for cardiac and respiratory causes (diagnoses at time of
      admission) to all major hospitals in the greater Athens area during 1988.
      Measurements of air pollution made by the Ministry of the Environment monitoring
      network included values for smoke, carbon monoxide, and nitrogen dioxide.
      Statistical analysis was done using multiple linear regression models controlling
      for potential confounding effects of meteorological and chronological variables,
      separately for winter (1/1-3/21 and 9/22-12/31) and summer (3/22-9/21). It was
      found that the daily number of emergency visits was related positively with the
      levels of air pollution, but this association did not reach the nominal level of
      statistical significance for most pollutants. The number of emergency admissions
      for cardiac and respiratory causes was related to a statistically significant
      degree with all indices of air pollution during the winter. Thus, the average
      adjusted increase in the daily number of cardiac admissions corresponding to an
      increase from the 5th to the 95th percentile of the season-specific distribution
      of each pollutant ranges from 15 to 17% or from 11 to 12.5 admissions per day,
      and for the daily number of respiratory admissions from 20 to 29% or from 8.3 to
      12.1 admissions. The results of the present study indicate that air pollution in
      the Athens area has short-term effects on morbidity in the population.

PMID- 7588490
TI  - Sulfuric acid aerosol followed by ozone exposure in healthy and asthmatic
      subjects.
AB  - These studies evaluated symptom and pulmonary function responses of humans
      sequentially exposed to sulfuric acid aerosol and ozone. Thirty healthy subjects
      and 30 allergic asthmatic subjects underwent 3-hr exposures in an environmental
      chamber to 100 micrograms/m3 sulfuric acid and sodium chloride (control) aerosols
      (in random order), followed 24 hr later by 3-hr exposures to ozone (0.08, 0.12,
      or 0.18 ppm). Each subject was studied four times, receiving each aerosol
      preexposure followed by two of the three ozone concentrations. For the healthy
      group, no convincing symptomatic or physiologic effects of exposure to either the
      aerosol or ozone on lung function were found. For the asthmatic group,
      preexposure to sulfuric acid altered the pattern of response to ozone in
      comparison with sodium chloride preexposure and appeared to enhance the small
      mean decrements in FVC that occurred in response to 0.18 ppm ozone (means +/- SE:
      -3.6 +/- 1.5% with sodium chloride preexposure, -6.8 +/- 1.7% with sulfuric acid
      preexposure). Individual responses among asthmatic subjects were quite variable,
      some demonstrating reductions in FEV1 of more than 35% following ozone exposure.
      Analysis of variance of changes in FVC revealed evidence for interactions between
      aerosol and ozone exposure both immediately after (P = 0.005) and 4 hr after (P =
      0.030) exposure. Similar effects were seen for FEV1. When normal and asthmatic
      subjects were combined, four-way analysis of variance revealed an interaction
      between ozone and aerosol for the entire group (P = 0.0022) and a difference
      between normal and asthmatic subjects (P = 0.0048). There was no significant
      effect of exposures on symptoms for either normal or asthmatic subjects.
      Asthmatic subjects differ from healthy volunteers in their functional responses
      following sequential exposures to aerosols and ozone and appear to represent a
      susceptible population.

PMID- 7588497
TI  - Dietary fat content and energy density during infancy and childhood; the effect
      on energy intake and growth.

PMID- 7588498
TI  - Effect of acetate and propionate on fasting hepatic glucose production in humans.
AB  - OBJECTIVE: Short chain fatty acids (SCFA, e.g. acetate and propionate) produced
      from bacterial colonic fermentation may be involved in the improvement of fasting
      glucose concentration observed with high dietary fibre diets. Because fasting
      blood glucose is related to hepatic glucose production, we have tested the effect
      of propionate and acetate on hepatic glucose production. SETTING: The study was
      carried out in the Clinical Research Center for Human Nutrition. SUBJECTS: Six
      healthy young volunteers. INTERVENTIONS: The subjects received, in a random
      order: acetate (12 mmol/h), or propionate (4 mmol/h), or acetate+propionate (12
      mmol/h + 4 mmol/h), or an isotonic sodium salt solution (saline) in 3 h gastric
      infusions. Blood glucose and plasma insulin was monitored. Hepatic glucose
      production was measured with an isotopic method using [6,6-2H2] glucose. RESULTS:
      No changes were observed in blood glucose, plasma insulin concentrations or
      hepatic glucose production with any of the infused solutions. An increase in free
      fatty acid (FFA) plasma concentration related to the fasting state was observed
      with the saline solution, but not with the SCFA infusions (P < 0.05). There was
      also an increase in beta-hydroxybutyrate concentration with the saline and the
      acetate solutions, but not with the propionate or acetate+propionate solutions.
      CONCLUSIONS: SCFA, administered at a rate calculated on the basis of a continuous
      daily fermentation of 30 g dietary fibres, do not change hepatic glucose
      production or fasting blood glucose. Propionate and acetate decrease plasma FFA,
      and further studies are needed to explore this effect on glucose tolerance and
      insulin sensitivity.

PMID- 7588499
TI  - Energy and macronutrient intake in growth hormone-deficient adults: the effect of
      growth hormone replacement.
AB  - OBJECTIVE: To assess the energy intake and the macronutrient composition of the
      diet in 25 growth hormone-deficient (GHD) patients before, and after 3 and 6
      months replacement with recombinant human growth hormone (rhGH). DESIGN: The
      study had a randomised double-blind placebo-controlled design. Energy intake was
      assessed by the 4-day food record and 24-h urine total nitrogen excretion was
      used as a check on the validity. The energy and macronutrient intake of the GHD
      patients at baseline were compared with the data obtained in the Dutch
      Nutritional Survey. Fat-free mass (FFM) and body fat (BF) were assessed by
      bioelectrical impedance analysis (BIA). Plasma thyroid hormones and insulin-like
      growth factor-I (IGF-I) were studied in relation to energy and macronutrient
      intake. SETTING: Department of Endocrinology, University Hospital Utrecht,
      Utrecht, The Netherlands. SUBJECTS: 25 GHD patients, aged 21-60 years. RESULTS:
      GHD adults, compared to controls, have a lower energy intake. During the first 3
      months of rhGH replacement therapy, there is a trend for energy intake to
      increase, no change in macronutrient intake, whereas plasma T3, IGF-1 and FFM
      increase and body weight does not change, hence BF decreases. The positive
      relationship between the increase in energy intake and the rise in plasma total
      T3 level during rhGH replacement therapy indicates that in addition to the GH
      induced changes the increase in energy intake and specifically in carbohydrate
      intake might contribute to the enhanced conversion of thyroxine. Protein intake
      calculated from the 4-day food record was significantly correlated with protein
      intake calculated from 24-h urine nitrogen. CONCLUSION: GHD patients have a lower
      energy intake. Notwithstanding the fact that FFM and plasma T3 increase and body
      weight does not change, a significant increase in energy intake is not found with
      the use of the 4-day food record method.

PMID- 7588500
TI  - Symptomatic response to varying levels of fructo-oligosaccharides consumed
      occasionally or regularly.
AB  - OBJECTIVE: To evaluate in 14 healthy volunteers the gastrointestinal tolerance to
      an indigestible bulking sweetener containing fructo-oligosaccharides (FOS).
      DESIGN: In order to mimic their usual pattern of consumption, FOS were ingested
      throughout the day either occasionally (once a week, first period) or regularly
      (every day, second period). In the two patterns of consumption, daily sugar doses
      were increased until diarrhoea and/or a symptom graded 3 (i.e. severe) occurred,
      or when subjects did not want to ingest more candies. SETTING: Clinical Nutrition
      Unit, Hopital Saint-Lazare, Paris. RESULTS: In both periods, the first symptom
      which occurred was excessive flatus (> 30 g FOS/day): borborygmi and bloating
      appeared at a higher level (> 40 g/day); lastly, abdominal cramps and diarrhoea
      occurred at a very much higher level (50 g/day). The volumes of hydrogen excreted
      in breath in response to the same load of FOS were not different between the two
      periods. CONCLUSIONS: Chronic consumption of FOS initiated cautiously with
      subsequent gradual increase did not improve tolerance, nor reduce breath
      excretion of hydrogen.

PMID- 7588501
TI  - Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid
      intake.
AB  - OBJECTIVES: The hypothesis tested was that menstrual discomfort, e.g.
      dysmenorrhoea, known to be prostaglandin-mediated, can be influenced by the
      dietary ratio of n-3 and n-6 polyunsaturated fatty acids. The prostaglandins
      derived from marine n-3 fatty acids are normally less aggressive and therefore
      expected to be associated with milder symptoms. DESIGN: The question was surveyed
      in an epidemiological study based upon self-administered questionnaires
      concerning menstrual history, present symptoms, general health, socioeconomic
      factors, and general dietary habits. Two (prospective) 4-day dietary records were
      used to estimate average daily nutrient intake. SUBJECTS: The subjects were
      recruited by advertising (about 220 volunteered); 181 healthy Danish women were
      selected, aged 20-45 years; they were not pregnant and did not use oral
      contraceptives. RESULTS: No correlations were found between socioeconomic or
      anthropometric data and menstrual problems. On the contrary certain dietary
      habits, e.g. low intake of animal and fish products, and intakes of specific
      nutrients, were correlated with menstrual pain. The average dietary n-3/n-6 ratio
      of women with menstrual pain was 0.24. It was significantly higher among those
      with low intake of B12 coincident with low intake of n-3 (0.42, P < 0.001) (chi
      square), with low n-3 intake coincident with low n-3/n-6 ratio (0.42, P < 0.005),
      and finally with low intake of B12 coincident with low n-3/n-6 ratio (0.47, P <
      0.001). CONCLUSION: The results were highly significant and mutually consistent
      and supported the hypothesis that a higher intake of marine n-3 fatty acids
      correlates with milder menstrual symptoms.

PMID- 7588503
TI  - Trans mono- and polyunsaturated fatty acids in human milk.
AB  - OBJECTIVE: The aim of the present study was to identify the trans isomers of C18
      fatty acids in some human milk samples. SUBJECTS: Ten human milk samples from
      French women were collected in a local milk bank in order to assess their trans
      mono and polyunsaturated fatty acids (PUFA) content. INTERVENTION: The fatty acid
      profile was examined using methyl and isopropyl ester derivatives. The
      combination of gas-liquid chromatography, high-performance liquid chromatography
      and silver nitrate thin-layer chromatography was needed to describe the detailed
      fatty acid compositions, including the trans isomers of unsaturated C18 fatty
      acids. RESULTS: All the samples contained trans isomers of C18:1 acid (mean level
      1.9 +/- 0.2% of total fatty acids), with trans vaccenic acid being the major
      isomer. The samples also contained various isomers of linoleic and alpha
      linolenic acid, but at lower levels. Trans isomers of PUFA are the same as those
      present in deodorised or deep-fried oils. One sample presented an abnormally high
      degree of isomerisation of alpha-linolenic acid (almost 50%). This was related to
      the dietary habit or consuming foods that were deep-fried in rapeseed oil. This
      milk sample also contained some cyclic fatty acid monomers. CONCLUSION: The human
      milk samples collected in this study contained some trans fatty acids, including
      isomers of essential fatty acids. This should be taken into account in the
      dietary intake of the newborn.

PMID- 7588504
TI  - Resistant starch has little effect on appetite, food intake and insulin secretion
      of healthy young men.
AB  - OBJECTIVE: This study investigated whether resistant starch types II and III are
      more satiating than glucose. DESIGN AND SUBJECTS: During 4 weeks 24 healthy male
      volunteers consumed a daily supplement with either glucose or high-amylose corn
      starch (RS2) or extruded and retrograded high-amylose corn starch (RS3) in a
      cross-over, single-blind, randomised and balanced study design. Each type of
      supplement was consumed for a week. In the first week each subject consumed the
      glucose supplement. The RS2 and RS3 supplements provided for 30 g resistant
      starch/day. At the end of weeks 2, 3 and 4, subjects rated their appetite each
      whole hour on a visual analogue scale. Food intake was measured 1 day/week using
      the 24-h recall method. Subjects collected 24-h urine during the last 2 days of
      weeks 2, 3 and 4 to determine C-peptide excretion as a measure for the 24-h
      insulin secretion. RESULTS: Supplementation with RS2 caused significantly (P <
      0.05) lower appetite scores than supplementation with RS3 and glucose, though
      subjects paradoxically felt less full while consuming RS2. The cyclic pattern of
      appetite during the day did not change with the supplements. Energy and
      macronutrient intake was similar in the three supplementation periods. When
      consuming RS3, subjects had a significantly (P < 0.0012) lower urinary C-peptide
      excretion than when consuming RS2 or glucose: 3.74 +/- 1.42 nmol/day for RS3,
      4.39 +/- 1.52 nmol/day for RS2 and 4.71 +/- 1.73 nmol/day for glucose. The
      mechanism for this lower insulin secretion is yet unclear. CONCLUSION:
      Consumption of 30 g/day RS2 and RS3 had little influence on appetite and food
      intake, but RS3 reduced the insulin secretion.

PMID- 7588505
TI  - Evaluation of a quantitative food frequency questionnaire used in a group of
      Norwegian adolescents.
AB  - OBJECTIVE: The study was conducted to assess the reproducibility and validity of
      a 190-item self-administered quantitative food frequency questionnaire, used in a
      nation-wide study of adolescents. DESIGN AND SUBJECTS: Reproducibility study; 103
      11th grade students (18 years) completed the questionnaire twice, with a 6-week
      interval. Validation study; 49 11th grade students filled in the questionnaire
      and kept 7-day weighed food records. RESULTS: Spearman rank correlations between
      the nutrient intakes from the two questionnaires varied from 0.63 (sugar energy
      percentage) to 0.91 (alcohol). The median coefficient was 0.85. The first
      questionnaire produced generally higher nutrient intake estimates than the
      second. Correlations between nutrient intake values from the records and the
      questionnaire ranged from 0.14 (vitamin D, non-significant, cod liver oil not
      included) to 0.66 (monounsaturated fatty acids). The median coefficient was 0.52.
      Adjustment for energy intake did not materially affect the correlations. On
      average 41% of the subjects were classified in the same quartile in the
      questionnaire and the records, and 2% in the opposite quartiles. However, the
      percentage of subjects in the same/opposite quartiles for vitamin D and fibre
      were 33/12 and 22/6, respectively. CONCLUSIONS: It is concluded that the
      questionnaire is able to rank subjects according to the tested nutrients, except
      vitamin D and fibre.

PMID- 7588502
TI  - Effects of oat gum on blood cholesterol levels in healthy young men.
AB  - OBJECTIVE: There is much evidence that oat products lower serum lipid
      concentrations in hypercholesterolaemic subjects. This effect has been attributed
      to the soluble fibre component of oat (1-->3)(1-->4)-beta-D-glucan. Therefore,
      the practical role of oat bran beta-glucan on serum lipid indices was examined.
      DESIGN: A metabolically controlled, randomised, single-blind, cross-over study.
      SETTING: Swiss Federal Institute of Technology, Department of Food Science and
      University Hospital, Zurich, Switzerland. SUBJECTS: 14 healthy young men,
      selected from university staff and students. INTERVENTIONS: After a 1-week run-in
      period subjects were randomly assigned to a test group (oat gum instant whip, 9 g
      beta-glucan/day) or a control group (placebo instant whip) for 14 days. After
      completing the first diet, subjects switched to the other diet for 14 days. The
      study was strictly metabolically controlled. Blood samples were collected for
      measurement of serum total cholesterol, HDL cholesterol, LDL cholesterol, and
      triglyceride concentrations. RESULTS: The dietary intake of the two groups was
      not significantly different. The body weights and physical activities of the
      subjects did not change significantly during the study. No statistically
      significant effect of the oat gum could be detected on serum total cholesterol,
      LDL cholesterol and triglyceride concentrations. HDL cholesterol was
      significantly higher (P < 0.05) during the test period. CONCLUSIONS: The
      cholesterol-lowering capacity of oat gum in healthy young men is weak. The effect
      of oat bran preparations on serum cholesterol levels cannot be estimated by the
      beta-glucan content but by measurement of the solubility and viscosity of the
      beta-glucan.

PMID- 7588506
TI  - Dietary intake among Norwegian adolescents.
AB  - OBJECTIVE: The aim of the nationwide study on dietary behaviour of adolescents
      was to describe and evaluate dietary habits, and relate that to other lifestyle
      factors. DESIGN AND SUBJECT: 1564 students in secondary schools completed a self
      administered quantitative food frequency questionnaire in a school setting.
      RESULTS: The questionnaire showed an average energy intake of 15.8 and 9.9 MJ
      among boys and girls, respectively. Nearly 31% of the energy was supplied by fat
      and 11.4% by sugar. The average daily intake of micronutrients exceeded the
      Norwegian recommendations, except for vitamin D and iron in girls. 13.4% of the
      students had breakfast twice a week or less. These students had a higher
      percentage of energy from fat and sugar, and a lower intake of micronutrients,
      than students eating breakfast more often. Students who were daily smokers or
      fairly inactive had higher energy percentage from fat and sugar and lower intake
      of fibre, than non-smokers or physically active students. CONCLUSION: Half of the
      students consumed a diet with too much fat and two-thirds consumed too much sugar
      as compared to the recommendations. The girls had a diet with a higher nutrient
      density and a lower fat energy percentage than the boys. Finally, it seemed as if
      a healthy lifestyle was associated with a healthy diet.

PMID- 7588507
TI  - An interactive 24-h recall technique for assessing the adequacy of trace mineral
      intakes of rural Malawian women; its advantages and limitations.
AB  - OBJECTIVES: To assess the relative validity of an interactive 24-h recall for
      estimating mineral intakes of rural Malawian women. DESIGN: Repeated interactive
      24-h recalls were compared with weighed records collected for the same 2 days of
      food intake, and for 2 days 1-2 weeks prior and subsequent to the weighed record
      data collection period. SETTING: Three villages in traditional authority Jalasi,
      Mangochi District, Malawi. SUBJECTS: 60 rural pregnant women. RESULTS: Median
      daily intakes of most minerals (Ca, Fe, Zn, Mn) were comparable for the two
      methods, but slightly overestimated for recalled (R) intakes expressed per MJ
      (mg/MJ) compared to weighed (W) (R vs W = Ca, 48 vs 38; Fe, 2.1 vs 1.9; Zn, 0.9
      vs 0.8; Mn, 0.40 vs 0.38; P < or = 0.05). By contrast, recalled median daily
      intakes of energy (kJ), protein (g) fat (g) and Cu (mg) were slightly
      underestimated (R vs W = 6588 vs 7824; 51 vs 57; 14 vs 15; 1.3 vs 1.6,
      respectively; P < or = 0.05). Discrepancies were attributed primarily to
      inaccurate estimates of main meal food portions [R vs W = nsima (the main meal
      cereal style) 475 vs 557; and legume relish 171 vs 118 P < or = 0.001]. For
      classifying intakes into tertiles, agreement between the two methods was poor for
      daily intakes (Cohen's kappa < 0.40), but fair when expressed per MJ, and as a
      percentage of energy from food groups (Cohen's kappa > or = 0.40). Variance
      ratios for recall data were higher than corresponding ratios for the weighed
      intakes (R vs W = for energy, 4.87 vs 0.87), indicating poorer recall measurement
      precision. CONCLUSION: Results emphasise the importance of selecting the dietary
      method according to the study objectives, and the nutrients required.

PMID- 7588508
TI  - Postprandial lipid and hormone responses to meals of varying fat contents:
      modulatory role of lipoprotein lipase?
AB  - OBJECTIVE: Substrate and hormone responses to meals of differing fat content were
      evaluated in normal subjects in order to investigate mechanisms underlying the
      regulation of postprandial lipoprotein concentration. DESIGN: A randomised cross
      over study with three different meals on three occasions. SETTING: Free-living
      subjects associated with Surrey University. SUBJECTS: Ten male volunteers (aged
      18-23 years) were recruited. INTERVENTIONS: Three test meals containing 20, 40 or
      80 g fat but identical carbohydrate and protein content were randomly allocated
      to volunteers. MAJOR OUTCOME MEASURES: Pre- and postprandial blood samples were
      taken for the analysis of plasma triacylglycerol, non-esterified fatty acids,
      glucose, immunoreactive insulin and glucose-dependent insulinotrophic polypeptide
      levels and postheparin lipoprotein lipase activity measurements. RESULTS: Peak
      triacylglycerol concentrations and lipoprotein lipase activity measurements were
      significantly higher following the 80 g than the 20 g fat meal (P = 0.009 and P =
      0.049 respectively). Areas under the glucose-dependent insulinotrophic
      polypeptide time-response concentration curves were significantly higher
      following the 80 g compared with the 20 g fat meal (P = 0.04), but no differences
      in insulin response to the meals were seen. The 30-360 min decrease in the non
      esterified fatty acid concentration was less following the 80 g than the 20 g
      meal (P = 0.001). CONCLUSIONS: The results suggest that glucose-dependent
      insulinotrophic polypeptide may mediate increased lipoprotein lipase activity in
      response to fat-containing meals and may play a role in circulating lipoprotein
      homeostasis. This mechanism may be overloaded with high fat meals with adverse
      consequences on circulating triacylglycerol and NEFA concentrations.

PMID- 7588511
TI  - Diet and nutritional status in children with cow's milk allergy.
AB  - OBJECTIVE: The purpose of this study was to investigate the nutritional status
      and adequacy of the diet in the children with cow's milk allergy (CMA). DESIGN
      AND SUBJECTS: 18 children with challenge-proven CMA and 20 healthy children were
      investigated in the cross-sectional study. The mean (range) age of the children
      was 2.0 (1.0-3.5) years. The healthy children were matched by age and sex with
      the allergic children. Food consumption data were collected by the six-day food
      record method. The weight and height of both groups and laboratory indices of
      children with CMA were measured to study the nutritional status. RESULTS:
      Thirteen (72%) of the children with CMA used a formula based on soy or casein
      hydrolysate. The amounts of these formulas consumed by the allergic children were
      smaller (371 ml vs 559 ml; P < 0.01) than the amount of milk and milk products
      consumed by the healthy children. There was no difference in energy intake
      between the groups. Protein intake by the allergic children was lower (39 g vs 48
      g; P < 0.05) and fat intake higher (47 g vs 39 g; P < 0.05) than that of the
      healthy children. The mean intakes of energy and zinc in both groups, and the
      intake of iron in the healthy children, were below the RDAs. The diet in the
      allergic children was supplemented with calcium and in 11 children with vitamins
      A and D. Fourteen healthy children had vitamin A and D supplement. The height-for
      age was lower in the children with CMA (-0.6 vs +0.2 s.d. units; P < 0.05) as
      compared to healthy children. Serum biochemical measurements were within the
      reference range in the allergic children, and no nutritional problems were found.
      CONCLUSIONS: For the eliminated foods children with CMA substituted nutritionally
      corresponding food items which resulted in adequate mean intakes of nutrients.
      Specific formulas contributed substantially to the nutrient intake. Children with
      CMA need intensive nutritional counselling and regular monitoring of growth.

PMID- 7588509
TI  - Excretion of amino acid residues from diets based on low-fibre wheat or high
      fibre rye bread in human subjects with ileostomies.
AB  - OBJECTIVES: The effect of consumption of a wheat-flour bread-based low-fibre diet
      (13.6 g/day fibre per portion) or a rye bran bread and whole-grain rye crispbread
      based high-fibre diet (43.5 g/day fibre per portion) on the ileal excretion of
      amino acid residues and crude protein was studied. DESIGN: The study was
      performed as a cross-over design. SETTING: The subjects were studied as
      outpatients except on the sampling days when all subjects were admitted to the
      research ward and stayed in a nearby patient hotel overnight. SUBJECTS: Six men
      and two women, all proctocolectomised for ulcerative colitis, volunteered to
      participate in the study. INTERVENTIONS: During each dietary period of 3 weeks,
      food and excreta were collected and analysed on days 3, 17 and 18. RESULTS: The
      excretion of crude protein and amino acids (free and bound) was generally higher
      during the high-fibre diet period, although the relative proportion of amino
      acids was similar in the ileal effluents from the two diets. The apparent
      digestibilities of crude protein and all amino acids except histidine, tyrosine
      and proline were significantly (P < 0.05) lower during the high-fibre diet
      period. CONCLUSION: It was indicated that the effect of the high-fibre rye-based
      diet was a generally impaired ileal amino acid absorption.

PMID- 7588512
TI  - Biochemical assessment of nutritional status in pre- and post-natal Turkish women
      and outcome of pregnancy.
AB  - OBJECTIVE: To determine by biochemical methods the nutritional status of pre- and
      post-natal Turkish women and its relationship with offspring anthropometry.
      DESIGN: Longitudinal study. SETTING: Health centres in Istanbul and Izmit,
      research department and university hospital laboratories. SUBJECTS: Randomly
      selected group of women attending health centres at 13-17 weeks gestation (n =
      130); same sample of women at 28-32 weeks gestation (n = 88) and 13-17 weeks post
      partum (n = 95); offspring at 13-17 weeks post-partum (n = 90). INTERVENTIONS:
      Blood samples taken from mothers at all three stages and analysed for ferritin,
      iron, zinc, calcium, alkaline phosphatase, total protein, albumin, vitamins B2,
      B6, B12, A, E, beta-carotene and folate levels; questionnaire completed for
      recording medical and socio-demographic background. Anthropometric measurements
      taken from mothers and offspring. RESULTS: High percentages of subjects were at
      risk for deficiencies of vitamin B12 (48.8%) and folate (59.7%) in early
      pregnancy; ferritin (52.3%), zinc (72.3%), vitamin B2 (38.8%), vitamin B12
      (80.9%), and folate (76.4%) during late pregnancy; and ferritin (39.0%), vitamins
      B2 (43.1%), B6 (36.4%), B12 (60.0%), and folate (73.3%) at the post-partum stage.
      Bone loss was indicated in 55.0% and 80.0% of the subjects in late pregnancy and
      post-partum respectively. Haematocrit in later pregnancy correlated strongly with
      prenatal body fat (P < 0.001). Infant anthropometry at 13-17 weeks post-partum
      was significantly affected by pre-natal weight gain and a number of maternal
      blood nutrients in pregnancy and post-partum. CONCLUSIONS: Nutrition education
      programmes and enrichment of the staple food with iron, zinc, calcium, and the B
      vitamins should be considered.

PMID- 7588510
TI  - Excretion of amino acid residues from diets based on wheat flour or oat bran in
      human subjects with ileostomies.
AB  - OBJECTIVES: The effect of consumption of a wheat-flour bread-based low-fibre diet
      (7.8 g/day fibre; 1.0 portion) or the same diet in which the wheat bread was
      exchange for a bread based on oat bran with a high fibre content (31.9 g/day
      fibre; 1.0 portion) on the ileal excretion of amino acid residues and crude
      protein was studied. DESIGN: The study was performed as a cross-over design.
      SETTING: The subjects were studied as outpatients except on the sampling days
      when all subjects were admitted to the research ward and stayed in a nearby
      patient hotel overnight. SUBJECTS: Seven men and three women, all
      proctocolectomised for ulcerative colitis, volunteered to participate in the
      study. One female subject was withdrawn from the study because of inflammation of
      the ileal stoma. INTERVENTIONS: During each dietary period of 3 weeks, food and
      excreta were collected and analysed on days 3 and 17. RESULTS: No significant
      differences in excretion of crude protein or amino acids (free and bound) were
      found between the two sampling days. Intake as well as excretion of all analysed
      amino acids was higher during the high-fibre diet period, although the relative
      proportion of amino acids was comparable in the two diets and their corresponding
      ileal effluents. Aspartic acid, glycine, threonine, alanine and serine were found
      in considerably higher relative proportions in the effluents from the subjects
      when they consumed each of the two diets than their concentrations in the diets.
      The apparent digestibilities were significantly (P < 0.05) lower for all analysed
      amino acids during the high-fibre diet period. Aspartic acid (10.7%), alanine
      (9.9%) and glycine (8.5%) showed a more pronounced decrease than the mean
      decrease in amino acid digestibility (6.6%) when subjects consumed the high-fibre
      diet. CONCLUSION: Intake of the oat bran high-fibre diet resulted in
      significantly lower amino acid and crude protein digestibility. The relative
      amino acid proportions in the diets and their corresponding excretas were,
      however, comparable for the two diets.

PMID- 7588514
TI  - Microchip electrophoresis with sample stacking.
AB  - A fused quartz microchip with a serpentine column geometry is fabricated to
      perform rapid microchip electrophoresis of dansylated amino acids. A 67 mm
      separation column is constructed in a 7 x 10 mm area on a quartz substrate using
      standard photolithographic, etching and deposition techniques. Buffer and sample
      flows within the channel manifold are precisely controlled through potentials
      applied to the reservoirs. To enhance the detection limits, a stacking injection
      technique is used to concentrate the sample at the inlet of the separation
      column. The stacked injections exhibit high reproducibility (2.1% relative
      standard deviation in peak area). Using a separation length of 67 mm and a
      separation field strength of 1100 V/cm, separations are performed in < or = 15 s
      generating approximately 40,000 theoretical plates.

PMID- 7588513
TI  - Separation and detection of amino acids and their enantiomers by capillary
      electrophoresis: a review.
AB  - Since its introduction as an analytical technique capillary electrophoresis has
      been used for the separation of amino acids and their enantiomers; over 150
      studies have been published to date. This review deals with their separation and
      detection. Amino acids have been resolved using both capillary zone
      electrophoresis and micellar electrokinetic chromatography. Pre-column
      derivatization schemes which are employed for the sensitive detection of amino
      acids are discussed. Criteria for the selection of the pre- or post-column
      derivatizing agent, chromophore or fluorophore, are presented. Detection systems,
      direct and indirect, that have been used are given with emphasis on fluorogenic
      reagents and laser induced fluorescence detection. Also, procedures for the
      separation of amino acid enantiomers are discussed and illustrated.

PMID- 7588515
TI  - Determination of amino acids by on-line capillary electrophoresis-electrospray
      ionization mass spectrometry.
AB  - On-line capillary electrophoresis-electrospray ionization mass spectrometry (CE
      ESMS) has been used for the separation and detection of amino acid mixtures. Four
      natural amino acids, histidine, tryptophan, phenylalanine, aspartic acid, and a
      tripeptide, glutathione, were separated and determined. Protonated molecules were
      detected in the CE-ESMS mode with detection limits of about one pmol. Optimum CE
      ESMS operating conditions for amino acid analysis were determined employing
      acetic acid solutions as CE electrolytes. The examined parameters included
      capillary diameter (50-100 microns internal diameter), applied separation voltage
      (20-30 kV), and concentration of electrolyte (10-60% acetic acid). Stable working
      conditions were maintained when the CE currents were less than 18 microA. The use
      of electrolyte solutions such as those described here instead of true buffer
      solutions may have advantages for CE-ESMS systems which employ a "sheathless"
      interface.

PMID- 7588518
TI  - Enantiomeric separation of amino acids using micellar electrokinetic
      chromatography after pre-column derivatization with the chiral reagent 1-(9
      fluorenyl)-ethyl chloroformate.
AB  - Direct enantiomeric separations of some racemic amino acids derivatized with 9
      fluorenylmethyl chloroformate were obtained using cyclodextrin-modified micellar
      electrokinetic chromatography (CD/MEKC) with a buffer made up of 5 mM sodium
      borate (pH 9.2), 150 mM sodium dodecyl sulfate (SDS) and 40 mM gamma-CD.
      Alternatively, enantiomeric separations were also achieved indirectly using MEKC
      after pre-column derivatization with (+)-1-(9-fluorenyl) ethyl chloroformate
      (FLEC). Using either a 10 mM sodium phosphate (pH 6.8) or a 5 mM sodium borate
      buffer (pH 9.2), each of which contained 25 mM SDS and 10-15% of acetonitrile,
      FLEC-derivatized serine, alanine, valine, methionine, leucine, phenylalanine,
      tryptophan, and their diastereomeric pairs were all separated: the L-isomers
      migrated faster than the corresponding D-isomers. However, when (-)-FLEC was used
      for derivatization, the D-isomers migrated faster than the corresponding L
      isomers. Also, the diastereomers of aspartic acid, glutamic acid, and proline
      were resolved using a 10 mM sodium citrate buffer (pH 4.4). Using KrF (248 nm)
      laser-induced fluorescence, the detection limit of (+)-FLEC derivatized DL-amino
      acids was obtained at the nM level, which was about 100 x more sensitive than UV
      absorption at 200 nm. Analyte concentrations as low as 3 x 10(-8) M (DL-Val)
      could be derivatized with (+)-FLEC.

PMID- 7588520
TI  - Effect of pH and ionic strength of running buffer on peptide behavior in
      capillary electrophoresis: theoretical calculation and experimental evaluation.
AB  - The effect of pH and ionic strength of running buffer on peptide behavior in
      capillary electrophoresis (CE) is studied. A system for predictions of peptide
      migration in CE (SPPMCE) developed in our laboratory has been tested in a wide
      range of pH and buffer concentrations. The SPPMCE consists of a computer program
      for calculating peptide pKa values, an equation which relates peptide structures
      to their electrophoretic mobilities and a coupled computer program for the
      prediction of electropherograms. More than 25 different buffers have been
      employed, covering a pH range of 2-11 and a concentration range of 5-100 mM.
      Results from experiments are compared with the theoretical predictions. Good
      agreement is observed, which confirms the utility of the SPPMCE and allows fast
      and easy optimization of peptide separations in CE, with nothing more than the
      amino acid sequence of the linear peptide as the input.

PMID- 7588516
TI  - Analysis of underivatized amino acids by capillary electrophoresis using constant
      potential amperometric detection.
AB  - A mixture of native (underivatized) amino acids is separated by capillary
      electrophoresis under alkaline conditions (pH approximately 12) and
      amperometrically detected with a copper-disk microelectrode. A simple design
      facilitates capillary-electrode alignment without the need for micropositioning
      equipment. The limits of detection for the amino acids are in the low microM
      concentration range, and the signal response is linear over 2-3 orders of
      magnitude. This procedure is applied to analyze the amino acid hydrolysis
      products from cytochrome c.

PMID- 7588521
TI  - High performance capillary electrophoresis of casein phosphopeptides containing 2
      5 phosphoseryl residues: relationship between absolute electrophoretic mobility
      and peptide charge and size.
AB  - Multiple phosphoseryl-containing peptides from casein containing the cluster
      sequence -Ser(P)-Ser(P)-Ser(P)-Glu-Glu- stabilize amorphous calcium phosphate at
      neutral and alkaline pH and have been shown to be anticariogenic in various in
      vitro, animal and human experiments. In an approach to obtain insight into the
      structure and function of these peptides, we previously developed a method for
      their analysis using high-performance capillary electrophoresis (HPCE). A linear
      relationship was obtained between absolute electrophoretic mobility and q/M2/3
      where q is the net negative charge of the peptide calculated using relevant pKa
      values and M is the molecular mass. M2/3 is a measure of the surface area of a
      sphere that has a volume proportional to the M of the peptide and relates to the
      frictional drag exerted on the peptide during electrophoretic migration. To
      examine this relationship further, we have analyzed a range of high-performance
      liquid chromatography (HPLC)-purified cluster, di- and triphosphorylated peptides
      from casein enzymic (trypsin, alcalase and pancreatin) digests using HPCE and
      attempted to relate their absolute electrophoretic mobility to various models
      incorporating peptide size and charge. Absolute electrophoretic mobility of
      casein phosphopeptides containing the cluster sequence-Ser(P)-Ser(P)-Ser(P)-Glu
      Glu- was most closely correlated with q/M2/3. Di- and triphosphorylated peptide
      absolute electrophoretic mobility correlated with both q/M2/3 and ln(q+l)/n0.43.
      However, for both the q/M2/3 and In(q+l)/n0.43 relationships with absolute
      electrophoretic mobility, the di- and triphosphorylated peptides formed a
      separate linear relationship to that of the cluster peptides. From these
      relationships, a di- or triphosphorylated peptide exhibited a greater absolute
      electrophoretic mobility than a corresponding cluster peptide with sam q/M2/3 or
      In(q+l)/n0.43 value.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588517
TI  - Direct determination of amino acids by capillary electrophoresis/electrochemistry
      using a copper microelectrode and zwitterionic buffers.
AB  - Sixteen free amino acids were separated by capillary electrophoresis (CE) using
      zwitterionic buffers of pH 9.8 and detected amperometrically using a copper
      microelectrode. Low conductivity buffers make possible the use of higher buffer
      concentrations. This depresses the electroosmotic flow, leading to a better
      separation of the amino acids compared to that obtained using strong
      electrolytes. The use of zwitterionic buffers also minimizes the amount of Joule
      heating in the capillary leading to more efficient separations. Perhaps most
      importantly for electrochemical (EC) detection, these buffers reduce the noise
      due to high separation current at the EC detector. The increased signal-to-noise
      ratio (S/N) results in much better detection limits for amino acids than those
      reported previously for capillary electrophoresis/electrochemistry (CEEC) with a
      copper electrode. Detection limits ranged from 10 to 400 nM, and the response was
      linear over three orders of magnitude for most of the amino acids. The system
      demonstrated good long-term stability and reproducibility with a relative
      standard deviation (RSD) of less than 5% for both the migration time and peak
      current (n = 20). This method was employed for the determination of amino acids
      in urine and in brain microdialysate samples.

PMID- 7588519
TI  - Application of capillary electrophoresis to amino acid sequencing of peptide.
AB  - Separations of twenty phenylthiohydantoin (PTH) amino acids, and amino acid
      derivatives, resulting from the Edman degradation of peptides and proteins, were
      optimized for peptide sequencing by capillary electrophoresis. Manual sequencing
      of angiotensin II was performed by Edman degradation and capillary
      electrophoresis of the PTH amino acid obtained after each cycle. The results were
      compared with those of an automated conventional protein sequencer. Interfacing
      capillary electrophoresis with Edman degradation provides an additional option
      for protein sequencing.

PMID- 7588522
TI  - Determination of caseinomacropeptide with capillary zone electrophoresis and its
      application to the detection and estimation of rennet whey solids in milk and
      buttermilk powder.
AB  - The presence of rennet whey solids in milk powder and buttermilk powder could be
      detected by analyzing the caseinomacropeptide (6.7 kDa) content by capillary zone
      electrophoresis. A hydrophilically coated capillary was used in combination with
      6 M urea in a citrate buffer at low pH. Under these conditions, genetic A and B
      variants migrated as a single peak. This afforded a detection limit of 0.4% of
      rennet whey solids in combination with large volume injections and on-column
      isotachophoretic concentration of the sample. The detector response (UV at 214
      nm) was linear in the range of 1-20% rennet whey solids and the recovery of
      caseinomacropeptide was 98%. Pseudo-caseinomacropeptide, lacking the N-terminal
      Met-residue, could be separated from caseinomacropeptide, thus preventing false
      positive results for some types of acid buttermilk powder.

PMID- 7588523
TI  - Solid-phase fluorescent labeling reaction of picomole amounts of insulin in very
      dilute solutions and their analysis by capillary electrophoresis.
AB  - The fluorescent labeling of peptides at concentrations as low as 10(-8) M can be
      achieved by using a solid-phase reactor. Using oxidized insulin chain B as a test
      peptide, we demonstrate the use of an Immobilon CD membrane to capture and
      preconcentrate peptides. Insulin chain B can then be labeled with a fluorogenic
      reagent, 3-(2-furoyl)quinoline-2-carboxaldehyde, while it is still attached to
      the membrane. Unwanted fluorescent products (attributed to secondary reactions)
      can be washed away with methanol without significant removal of the labeled
      insulin chain B, which then can be extracted with a low pH buffer. The analysis
      by micellar electrokinetic capillary chromatography with post-column laser
      induced fluorescence detection (mass limit of detection of 2.4 x 10(-21) moles
      insulin chain B) results in electropherograms that show great improvement in
      terms of unwanted peaks and high number of theoretical plates (up to 20 million).
      The use of the solid-phase reactor allows easy handling of as little as 5
      picomoles of insulin chain B.

PMID- 7588524
TI  - Sensitivity enhancement and second-dimensional information from solid phase
      extraction-capillary electrophoresis of entire high-performance liquid
      chromatography fractions.
AB  - A novel separation technique is demonstrated for peptide analysis of entire 100
      microL high-performance liquid chromatography (HPLC) fractions in a single, low
      pH, capillary zone electrophoresis (CZE) separation. The method employs a hybrid
      capillary consisting of a removable inlet section containing a reverse-phase
      packing and a standard CZE bare-fused silica separation capillary. The packed tip
      allows sample to be concentrated at flow rates greater than 20 microL/min and
      released in a controlled manner for CZE separation. Separations are comparable to
      standard CZE with minor modifications in selectivity. Using a mixture of model
      peptides, the hybrid capillary is shown to effect enhancement in sensitivity of >
      or = 100-fold. Five fractions from the HPLC separation of peptides obtained from
      the digestion of bovine serum albumin (BSA) were analyzed by the solid phase
      extraction-capillary electrophoresis (SPE-CE) method which was shown to provide
      rapid second-dimensional information. Practical concentration limits of detection
      for peptides are calculated to be 1-10 ng/mL with this technology.

PMID- 7588525
TI  - Selective preconcentration for capillary zone electrophoresis using protein G
      immunoaffinity capillary chromatography.
AB  - Capillaries with 150 microns inner diameter were packed with a perfused protein G
      chromatographic support and used as immunoaffinity preconcentrators for capillary
      zone electrophoresis. Antibody was loaded onto the protein G support to form an
      immunoaffinity stationary phase. Injection of samples onto the column caused
      selective retention and preconcentration of antigen. Injection of appropriate
      buffers onto the column caused desorption of the antibody and antigen which were
      then separated by capillary zone electrophoresis. The combination was used on
      line and off-line. For on-line combination, a flow-gated interface coupled the
      two columns and allowed injection of desorbed zones onto the electrophoresis
      system. Off-line coupling required collection of desorbed fractions and then
      injection onto the electrophoresis system. Flow rates as high as 100 microL/min
      were used to load sample onto the affinity column. Desorbing flow rates had to be
      1 microL/min or less to prevent excessive dilution during desorption. Using the
      system, 1 mL insulin samples could be loaded onto the affinity column and
      desorbed in volumes as small as 1 microL for 1000-fold preconcentration. The use
      of the preconcentrator with serum samples spiked with insulin was demonstrated.

PMID- 7588526
TI  - Performance of amino-silylated fused-silica capillaries for the separation of
      enkephalin-related peptides by capillary zone electrophoresis and micellar
      electrokinetic chromatography.
AB  - Enkephalin-related peptides were separated at low pH in a capillary with
      covalently bonded aminopropyl groups. The peptides are electrostatically repelled
      from the capillary surface and much higher efficiencies and faster separations
      were achieved compared to separations using uncoated capillaries. At low pH the
      amino groups are protonated, which results in reversed electroosmosis. The
      influence of voltage and ionic strength on the mobility and the separation
      efficiency was studied. The repeatability of migration times within one day was
      very good with relative standard deviations of 0.3-0.7%. Increasing the pH
      decreased the electroosmosis, eventually turning towards the cathode in the pH
      range 5-6; the separation performance, however, was lower at higher pH. Neutral
      and anionic micellar agents were added to the background electrolyte at different
      concentrations; the enkephalins had weak association with the neutral micellar
      agents but were distributed to the anionic taurodeoxycholic acid (TDC) micelles,
      giving rise to changes in separation selectivities. Very high efficiencies were
      obtained for peptides with a low distribution to the TDC micelles, while the
      efficiencies were impaired for those with a strong association with the micelles,
      which may indicate a slow mass transfer in the association process.

PMID- 7588528
TI  - Capillary electrophoretic resolution of phosphorylated peptide isomers using
      micellar solutions and coated capillaries.
AB  - The addition of sodium dodecyl sulfate (SDS) micelles in the running buffer can
      be used to resolve mono- and diphosphorylated isomers of the insulin receptor
      peptide by capillary electrophoresis. The effect of SDS on peptide resolution is
      very dependent on pH. Complete resolution of three monophosphorylated isomers is
      achieved in uncoated capillaries filled with phosphate buffer containing 25 mM
      SDS and buffered at pH 6.1. Resolution of the diphosphorylated isomers can be
      significantly improved by using polyacrylamide coated capillaries. In coated
      capillaries electroosmotic flow is negligible and the migration order of the
      isomers is reversed. This allows for a longer period of interaction between the
      diphosphorylated isomers and the micelle and therefore selectivity is improved.
      Efficiency of all peptide isomers was also improved in coated capillaries due to
      reduced adsorption to the capillary wall.

PMID- 7588527
TI  - Capillary electroseparations of enkephalin-related peptides and protein kinase A
      peptide substrates.
AB  - The separations of enkephalin-related peptides and protein kinase A peptide
      substrates, with the common structural feature -Arg-Arg-X-Ser-Val-, were studied
      in micellar electrokinetic chromatography (MEKC) systems and compared with the
      capillary zone electrophoresis (CZE) mode. The influence of the magnitude and the
      direction of the electroosmotic flow on the selectivity was studied. Reversed
      electroosmosis was obtained by adding a hydrophobic amine, dimethyldodecylamine,
      to the background electrolyte; the amine forms cationic micelles with a low
      critical micelle concentration (0.3 mM). The neutral micellar agent, Brij 35,
      competes with the amine for adsorption sites on the capillary surface decreasing
      the reversed electroosmosis. In such a system, mixed cationic micelles are formed
      to which the peptides were not distributed at low pH, but an improved resolution
      was obtained due to the effects on electroosmosis. In systems containing the less
      hydrophobic amine dimethyloctylamine, in which probably no mixed micelles are
      formed, an improved separation of protein kinase A peptide substrates was
      obtained due to distribution to Brij 35 micelles. In separations of enkephalins,
      a high pH gave very low efficiencies due to surface-analyte interactions, and the
      best CZE separations were obtained at low pH. Changes in migration order were
      observed in the pH range 2-3, possibly due to differences in peptide pKa values
      or conformation changes of the peptides. The enkephalins were only to a small
      extent distributed to the Brij 35 micelles, but this improved the separation at
      pH 2 compared to the CZE mode.

PMID- 7588529
TI  - Separation of eleven angiotensin II analogs by capillary electrophoresis with a
      nonionic surfactant in acidic media.
AB  - Eleven angiotension II analogs of same chain length were separated by capillary
      electrophoresis at pH 2.0 with 200 mM Tween 20. All compounds except one pair of
      angiotensin II ([Sar1, Gly8]- and [Sar1, Val5, Ala8]-angiotensin II) were
      baseline-separated, even in the case of peptides with about the same total
      charge. The migration order of the angiotensin II analogs were determined by the
      hydrophobicity of the amino acid as long as the difference between amino acids of
      two peptides is the conservative change. From the study of pH dependency of the
      separation of these peptides, it was found that the conditions of a low
      electroosmotic flow under a low pH is effective for the separation of similar
      peptides.

PMID- 7588532
TI  - Effect of buffer composition on the migration order and separation of histone H1
      subtypes.
AB  - The effects of different buffer concentrations and compositions on the elution
      order and separation of H1 histone subtypes and their phosphorylated
      modifications isolated from several species was studied using high-performance
      capillary electrophoresis (CE). Various cations and anions were tested in an
      untreated silica capillary and low pH buffers, in the presence of the dynamic
      coating agent hydroxypropylmethyl cellulose. It was found that the cations and
      anions of buffers have a remarkable influence on both the efficiency and the
      selectivity of protein separations. A triethylammonium methanephosphonate system
      proved efficacious for the separation of rat histone subtype H1c from H1e and a
      perchlorate/triethylammonium phosphate system for the analysis of chicken and
      mouse linker histones. CE provides an attractive alternative to high-performance
      liquid chromatography and conventional gel electrophoresis.

PMID- 7588530
TI  - Fast, high-resolution (capillary) electrophoresis in buffers designed for high
      field strengths.
AB  - Capillary electrophoresis in conventional buffers and in 50 microns capillaries
      permits field strengths as high as 300-500 V/cm with acceptably low thermal zone
      deformation. However, still higher field strengths (up to at least 2000 V/cm) can
      be applied without a decrease in resolution if the experiments are performed in
      the buffers described in this paper. Characteristic of these buffers is their low
      electrical conductivity and yet satisfactory buffering capacity accomplished
      either (i) by selecting buffer constituents of relatively high molecular weight
      and small net charge or (ii) by fractionation of carrier ampholytes (originally
      introduced for isoelectric focusing experiments) into a series of narrow pH range
      fractions and using these fractions as buffers, or (iii) by selecting an
      ampholyte with two acidic groups and one basic group (or one acidic group and two
      basic groups) and with a pI value close to two of its pK values. In such buffers,
      aromatic carboxylic acids and proteins used as model substances could be analyzed
      rapidly. For instance, albumin and transferrin were separated at 30,000 V (1.99
      microA) in 15 cm long fused silica capillaries (50 microns ID) within 40 s and
      the carboxylic acids within 25 s. The resolution was similar to that obtained at
      standard voltage (5000 V; 0.33 microA), but the analysis time was reduced
      sixfold. Although not verified experimentally we also suggest the use of
      relatively high-molecular-weight polyoxyethylene derivatized with one acidic
      group (for instance, boric acid) and one basic group (an amine), both having the
      same pK value, which should afford both a very high buffering capacity and very
      low electrical conductivity (at low buffer concentrations).

PMID- 7588534
TI  - Fused-silica capillaries with surface-bound dextran layer crosslinked with
      diepoxypolyethylene glycol for capillary electrophoresis of biological substances
      at reduced electroosmotic flow.
AB  - This report is concerned with the introduction of novel surface modification
      involving the covalent attachment of branched, high molecular weight dextrans and
      subsequent crosslinking with polyether chains on the inner surface of fused
      silica capillaries with the aim of producing hydrophilic capillaries with reduced
      electroosmotic flow (EOF). Three different molecular mass dextrans, namely 45, 71
      or 150 kDa were covalently attached to the capillary surface, and subsequently
      crosslinked with diepoxypolyethylene glycol (PEG). This chemistry produced stable
      coating over a wide range of conditions including high and low pH aqueous
      solutions. Moreover, the various dextran-PEG-coated capillaries exhibited reduced
      electroosmotic flow. These features of the dextran-PEG coatings were useful for
      the separations of basic and acidic proteins, and provided high resolution
      separation for closely related acidic monosaccharides and sialooligosaccharides.

PMID- 7588531
TI  - Charge and size effects in the capillary zone electrophoresis of nuclease A and
      its variants.
AB  - The migration behavior of nuclease A from Staphylococcus aureus and 11 of its
      variants in capillary zone electrophoresis (CZE) was investigated in the light of
      their three-dimensional structure known from X-ray crystallography and nuclear
      magnetic resonance (NMR) measurements. Nuclease A (molecular mass 16.8 kDa, pKa
      10.3) and the variants differ only in a single amino acid residue and have a very
      similar crystal structure. With the use of coated quartz capillaries and suitable
      buffers, the protein migration was investigated at pH from 2.8 to 9.5 without
      interference by wall adsorption. Although the selectivity of the electrophoretic
      system for the proteins was mainly determined by their charge differences,
      certain variants having the same net charge could also be readily separated under
      nondenaturing conditions. For instance, the mobility of variant K116A was
      sufficiently higher than that of K116G so that they could be separated by CZE.
      The structures of both variants are the same except for the solvent-exposed loop
      containing residue 116. For this reason, the difference in electrophoretic
      mobilities can be attributed to the fact that in K116G the backbone of the 112 to
      117 amino acids protrudes slightly from the protein, with a concomitant increase
      in the hydrodynamic radius with respect to that of K116A. Consequently, K116G
      shows a smaller mobility than K116A due to its larger hydrodynamic radius despite
      its smaller molecular mass. The interpretation of the experimentally measured
      mobilities of such closely related proteins therefore requires not only
      consideration of their electrostatic charge but also the fine details of their
      molecular structures.

PMID- 7588535
TI  - High-performance capillary electrophoretic separation of proteins and peptides
      using a bonded hydrophilic phase capillary.
AB  - High performance capillary electrophoresis (HPCE) was applied to the separation
      of protein and peptide mixtures with molecular masses ranging from 1300 to 96000
      Da using a new bonded hydrophilic phase capillary, CElect-P150. This coated
      capillary reduces the interaction between proteins and silanol groups in
      capillary walls, allowing a complete recovery of the proteins and peptides of
      interest. HPCE was also used for the analysis of a complex mixture of tryptic
      fragments and to monitor the process of enzymatic digestion. Moreover, using a
      CElect-P150 capillary, highly reproducible analysis was possible without
      preconditioning the capillary with acid or basic solutions before each new
      analysis.

PMID- 7588533
TI  - On the separation mechanism of capillary sodium dodecyl sulfate-gel
      electrophoresis of proteins.
AB  - Polyethylene oxide-mediated capillary sodium dodecyl sulfate-electrophoresis is a
      recently established, high-resolution separation method for fast purity check and
      molecular mass assessment of protein molecules. The effects of the sieving
      polymer chain length and concentration on the separation mechanism of sodium
      dodecyl sulfate-protein complexes were examined. The studies aimed to clarify
      whether the separation can be described by either the Ogston sieving theory, or
      the reptation or reptation-with-stretching theory. Polyethylene oxides with
      molecular masses of 100,000, 300,000 and 900,000 Da were used as separation
      matrices at various concentrations ranging from 1-4%, 0.5-2% and 0.25-1%,
      respectively. The separation phenomena was examined using a standard protein test
      mixture containing six proteins in the molecular mass range of 14,200-97,400 Da.
      A possible separation mechanism of reptation with stretching is suggested, where
      separation performance was improved with increasing sieving polymer chain lengths
      and/or concentration.

PMID- 7588536
TI  - N,N,N',N'-tetramethyl-1,3-butanediamine as effective running electrolyte additive
      for efficient electrophoretic separation of basic proteins in bare fused-silica
      capillaries.
AB  - The effect of N,N,N',N'-tetramethyl-1,3-butanediamine (TMBD) in the running
      electrolyte on the electroosmotic flow and the migration behavior of four
      standard basic proteins in bare fused-silica capillaries was examined at pH 4.0,
      5.5, and 6.5. Depending on the electrolyte pH and additive concentration the
      electroosmotic flow was either cathodic or anodic. A similar Langmuirian-type
      dependence of the electroosmotic flow on the concentration of TMBD in the running
      electrolyte was found at the three experimented pH values, which may be
      indicative of the specific adsorption of the additive in the immobilized region
      of the electric double layer at the interface between the capillary wall and the
      electrolyte solution. Electrophoretic separations of the four standard basic
      proteins performed at the three above pH values, showed well-resolved, efficient
      and symmetric peaks, demonstrating the utility of this additive for protein
      electrophoresis in bare fused-silica capillaries. The variations in separation
      efficiency, peak capacity, resolution and reproducibility of migration times as a
      function of the additive concentration at pH 6.5 were also examined.

PMID- 7588538
TI  - Capillary electrophoretic separations of biotechnology-derived proteins in E.
      coli fermentation broth.
AB  - A capillary electrophoresis (CE) method was developed for the analysis of a
      recombinant DNA protein in a fermentation broth matrix. A polyacrylamide-coated
      capillary was employed to eliminate electroosmotic flow, facilitating relatively
      rapid run times. Selectivity and efficiency were enhanced significantly through
      the incorporation of magnesium sulfate and acetonitrile, an organic modifier,
      into the separation buffer. Both of these additives appeared to influence the
      separation by diminishing the interaction of the protein analyte with the charged
      micelles present in the buffer. The quantitation capabilities of the CE method
      were validated and found to be comparable to the standards set by chromatographic
      techniques previously developed for similar applications.

PMID- 7588537
TI  - Analysis of immunoglobulin G using a capillary electrophoretic affinity assay
      with protein A and laser-induced fluorescence detection.
AB  - A method for the rapid and sensitive determination of immunoglobulin G (IgG) in
      cultivation media by an affinity assay using capillary electrophoresis is
      presented. For that purpose we evaluated protein A conjugated with a fluorescent
      dye such as fluorescein diisocyanate or dichlorotriazinyl-aminofluorescein as an
      affinity ligand. The ligand formed a fluorescing complex with immunoglobulin G in
      the sample and rapid separation from excess protein A was performed by capillary
      zone electrophoresis. However, only partial resolution of the zones was achieved
      when protein A as a whole molecule was utilized. In contrast, baseline resolution
      of the zones was obtained when recombinant fragments of protein A were used as
      affinity ligands. Immunoglobulin concentrations in the range of two orders of
      magnitude were determined. Due to the specificity of protein A for immunoglobulin
      G, analysis can be carried out even in the presence of high concentrations of
      other components and in cultivation media. Thus, the capillary electrophoretic
      affinity assay was successfully applied to monitor monoclonal antibodies in a
      cultivation process.

PMID- 7588541
TI  - Separation of arginase isoforms by capillary zone electrophoresis and isoelectric
      focusing in density gradient column.
AB  - Four major arginase isoforms, I, II, III and IV, have been detected in Evernia
      prunastri thallus. They differ in terms of both physical and biochemical
      properties. The isoelectric point (pI) of these proteins has been determined by
      both isoelectric focusing in density gradient column and high-performance
      capillary electrophoresis (HPCE). Isoelectric focusing revealed charge
      microheterogeneity for isoforms II and IV whereas arginases I and II had the same
      pI value of 5.8. HPCE separation confirmed this charge microheterogeneity for
      isoform IV but not for isoform III, and provided evidence of microheterogeneity
      for isoforms I and II. The effect of various electrolyte buffers and running
      conditions on the HPCE separation of arginase isoform were investigated. Addition
      of 0.5 mM spermidine (SPD) to the running buffer reduced the electroosmotic flow
      (EOF) and permitted discriminating between the native proteins and protein
      fragments.

PMID- 7588540
TI  - Quantitative analysis of major whey proteins by capillary electrophoresis using
      uncoated capillaries.
AB  - A method that allows separation and quantitation of the main whey proteins by
      capillary electrophoresis using uncoated capillaries is proposed. Separations are
      performed using 100 mM borate buffer, pH 8.2, containing 30 mM sodium sulfate.
      The use of high pH and high ionic strength buffer reduces adsorption of proteins
      on the capillary wall, making their separation possible. Reproducibility of
      migration times and areas of peaks are improved by optimizing the capillary
      equilibration protocol and by using an internal standard. Relative standard
      deviations ranging between 0.74 and 1.03% for migration times and 2.14 to 5.23%
      for areas of major peaks are obtained. Detection limits equal to or lower than
      0.5 mg/100 mL are achieved. Linear relationships of peak area versus
      concentration have been used to quantitate bovine serum albumin (BSA), alpha-LA
      (alpha-lactalbumin), beta-LG A (beta-lactoglobulin A) and beta-LG B (beta
      lactoglobulin B) in cow's milk subjected to different thermal treatments.
      Electrophoretic profiles of these milk samples show peaks from other peptides
      besides those from main proteins. Characteristic patterns for whey from different
      species are obtained.

PMID- 7588539
TI  - Analysis of recombinant human tumor necrosis factor beta by capillary
      electrophoresis.
AB  - Capillary electrophoresis was used for the analysis of recombinant human tumor
      necrosis factor beta (rhTNF-beta). Reproducible separation of the protein could
      be achieved in Polybrene-coated capillaries. Optimum conditions for separation
      were achieved with a pH 4.5 sodium acetate buffer. Besides Polybrene-coated
      capillaries, other commercially available column and column-coating reagents were
      also examined for the separation of rhTNF-beta. Capillary electrophoresis was
      found to be a potentially useful method for product analysis and process
      monitoring in recombinant-DNA technology.

PMID- 7588542
TI  - Application of capillary isoelectric focusing with absorption imaging detection
      to the quantitative determination of human hemoglobin variants.
AB  - The capillary isoelectric focusing (CIEF)-absorption imaging detector is a
      multicapillary separation instrument. Several protein samples can be separated
      and detected in a single run. The analysis time for one run is only 3 min.
      Because an imaging detector is used, the mobilization process of conventional
      CIEF is not necessary, eliminating such drawbacks as long analysis time and poor
      reproducibility in mobilization speed. Human hemoglobin variants were
      quantitatively determined using the instrument. The peak areas of the analytes
      were proportional to their concentrations in the concentration range of 0-200
      micrograms/mL. Hemoglobin variant A2, which only comprises 2% of the whole
      hemoglobin, can be quantitatively determined with a standard deviation of less
      than 10%. For the high concentration variants, such as variant S, the deviation
      is less than 1%.

PMID- 7588543
TI  - Simple and sensitive laser-induced fluorescence detection for capillary
      electrophoresis and its application to protein separation.
AB  - A low-cost and highly sensitive laser-induced fluorescence detector for on-column
      detection systems was constructed and its applications were demonstrated in
      protein separation by capillary electrophoresis. The limit of detection (LOD) at
      a signal-to-noise ratio of 2 for Lissamine 20 was about 1.4 x 10(-21) mole at 10
      nL sample injection and the relative standard deviation (RSD) for 1.5 x 10(-11) M
      of Lissamine 20 solution was about 15%. These values are comparable to or even
      better than those reported using a similar on-column detection system. This
      sensitive LIF detection was applied for the study of tryptic digestion of insulin
      and for urinary protein profiling.

PMID- 7588544
TI  - Electrophoresis forum '94. Proceedings of the international meeting. Munich,
      October 24-26, 1994.

PMID- 7588545
TI  - Indirect DNA/gene diagnoses via electrophoresis--an obsolete principle?
AB  - In principle, gene defects can be investigated directly or indirectly via
      informative polymorphisms in their vicinity. But because many defects are not yet
      defined molecularly, these inherited diseases can only be diagnosed indirectly
      via analysis of informative family situations. Since (multiple) mutation
      analyses, e.g. via DNA sequencing, are time-consuming and expensive, indirect
      analysis may still be performed initially--particularly in diseases caused by
      heterogenous mutations. We focus on diagnoses of neurological and (auto)immune
      diseases by polymerase chain reaction and separation of the DNA fragments via gel
      electrophoreses. Even after gene defects have been identified, indirect analysis
      might be necessary, for example in Huntington's chorea. Although this genetic
      defect has been characterized as a trinucleotide disease, indirect DNA diagnosis
      is still performed in particular cases for psychological reasons. The causes of
      autoimmune diseases are multifactorial and the inheritance is complex, involving
      several genes. Genome-wide screening programs may involve indirect approaches via
      analyses of polymorphic microsatellites. Large parts of the immunological genome
      can be covered when 20 or more genes are investigated simultaneously. Thus the
      genetic bases of autoimmune diseases are disclosed. Microsatellites themselves
      could have a biological meaning. We therefore discuss also DNA/protein
      interactions for simple tandem repeats, the major targets for indirect gene
      diagnoses. Only indirect evidence exists that certain simple repeats influence
      genomic (in)stability. Taken together, indirect gene diagnoses supplement direct
      approaches in a variety of different purposes and in combination with standard
      electrophoresis techniques.

PMID- 7588546
TI  - Use of polyacrylamide gel electrophoresis to detect structural variations in
      kilobase-sized DNAs.
AB  - The electrophoresis of linear, kilobase-sized DNA molecules with permuted
      sequences has been studied in polyacrylamide and agarose gels. Plasmid pBR322,
      bacteriophage phi X174, and the SV40 minichromosome were each digested with a
      series of single-cut restriction enzymes. The linearized, permuted isomers of all
      three DNAs exhibit different mobilities in large-pore polyacrylamide gels,
      suggesting that all three DNAs contain sites of anisotropic, sequence-dependent
      curvature. Various experimental parameters such as acrylamide concentration,
      crosslinker ratio and buffer composition affect the magnitude of the observed
      differential mobilities. Band sharpness appears to be optimal in polyacrylamide
      gels containing 6.9-8.1%T and 0.5-1%C. Only small mobility differences are
      observed for the linearized, permuted sequence isomers in agarose gels.

PMID- 7588549
TI  - Commercial automated gel electrophoresis apparatus: application to DNA, band
      dispersion, nonlinear Ferguson curves, and isolation.
AB  - Recently available commercial automated gel electrophoresis apparatus with
      intermittent scanning of fluorescently labeled gel patterns (the HPGE-1000
      apparatus of LabIntelligence, Menlo Park CA) was tested with regard to (i) its
      applicability to DNA in its native conformation, (ii) its ability to recognize
      the correct number of components, (iii) its capability to evaluate the width and
      shape of bands detected during electrophoresis, (iv) its ability to yield
      nonlinear Ferguson plots in a labor-saving fashion, and (v) its preparative
      potential. Ethidium homodimer (EtD) DNA (bp) ratios were systematically varied
      and the mobility of DNA fragments labeled at each ratio was measured in order to
      find a ratio which provided an unaltered mobility and presumably therefore an
      unaltered conformation of the fragment. That ratio was found to be 1/40 EtD/DNA
      (bp) or less. With such weak labeling of DNA, a representative fragment of 527 bp
      length requires a minimum load of 200 ng and a 2 micrograms load for a full-scale
      peak height. Using the baseline automatically selected by the software of the
      apparatus, the band areas of the 17 components of a DNA digest were consistently
      evaluated by the software, as evidenced by the proportionality between DNA length
      and area. The areas of the separated bands of DNA fragments of 1857 and 121 bp
      length were found to be constant with time of electrophoresis. The dispersion
      coefficient was found to decrease with agarose concentration in electrophoresis
      at 1 V/cm; however, at higher field strength, the band width of the 1857 bp
      fragment was surprisingly found to increase with gel concentration, presumably
      due to stretching.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588550
TI  - Detection of two hypervariable (ATTTT)n loci in the human genome.
AB  - Object of this investigation was the isolation of a single-locus probe from a
      multi-locus fingerprint. Individual specific multi-locus fingerprints in man were
      generated by using the oligonucleotide probe (ATTTT)5. An isolated (ATTTT)5
      positive DNA fragment was analyzed using polymerase chain reaction (PCR) cycle
      sequencing and nonradioactive direct-blotting electrophoresis. A digoxigenated
      oligonucleotide synthesized according to this sequence was used as a single-locus
      probe. Two hypervariable loci were detected on Southern blots. Formal genetic
      investigations for the two loci were performed in order to estimate the allele
      frequencies. Locus 1 shows an individual-specific banding pattern with an
      autosomal-codominant inheritance and can be used for forensic investigations.
      Locus 2 also represents a polymorphic pattern, but the inheritance is not
      according to the Mendelian rules. Probably we have detected a highly mutagenic
      locus in the human genome.

PMID- 7588551
TI  - Temperature-gradient gel electrophoresis as a screening tool for polymorphisms in
      multigene families.
AB  - Information about sequence variability between different copies of a multigene
      family is indispensable for understanding the evolutionary mechanisms acting on
      multigene families. However, their high copy number has been a major obstacle to
      systematic analysis. Exemplified by the internal transcribed spacer 1 (ITS1) of
      the rDNA in Drosophila melanogaster, it is shown how temperature gradient gel
      electrophoresis (TGGE) can be used to study sequence polymorphisms in a multigene
      family. Experimental conditions influencing the melting behavior of the ITS1
      fragment are discussed as well as discrepancies between observed and calculated
      melting patterns.

PMID- 7588548
TI  - Trapping gel electrophoresis of end-labeled DNA: an analytical model for mobility
      and diffusion.
AB  - As shown by Ulanovsky, Drouin and Gilbert (Nature 1990, 343, 190-192), the gel
      electrophoretic migration of DNA is severely reduced by steric trapping when
      streptavidin is attached to one end of the polyelectrolyte. We present a model
      that allows us to calculate both the mobility and the diffusion coefficient,
      hence the resolution factor of the resulting separation. We compare our results
      to those of Defontaines and Viovy (Electrophoresis 1993, 14, 8-17) and we show
      that the averages over the molecular conformations must be done carefully. We
      also show that trapping increases diffusion substantially and that this makes
      constant-field trapping electrophoresis incapable of increasing the number of
      bases read per sequencing run. Finally, we conclude that severe trapping may lead
      to highly anomalous transport behavior where one cannot define a velocity or a
      diffusion constant.

PMID- 7588547
TI  - Effect of spike pulses on the orientation of the agarose gel matrix.
AB  - The orientation of the agarose gel matrix in two-part, "stair-step" electric
      fields has been studied by transient electric birefringence. Stair-step electric
      fields are those in which a pulse of a given amplitude is immediately followed by
      a short, higher voltage "spike" pulse of the same polarity. A single stair-step
      pulse orients the agarose gel matrix as though the two portions of the pulse were
      individually applied to the gel. However, a series of consecutive stair-step
      pulses causes an anomalous increase in the amplitude of the birefringence,
      suggesting that increased numbers of agarose fiber bundles are orienting in the
      electric field. Spike pulses > or = 10 V/cm appear to cause junction zone
      breakdown, freeing large numbers of agarose fiber bundles and microgel domains
      from the constraints of the gel matrix. The implications of these results for
      pulsed field gel electrophoresis are discussed.

PMID- 7588553
TI  - Temperature gradient gel electrophoresis for analysis of a polymerase chain
      reaction-based diagnostic clonality assay in the early stages of cutaneous T-cell
      lymphomas.
AB  - By means of a multiplex polymerase chain reaction (PCR) we amplified rearranged T
      cell receptor gamma chain genes to detect monoclonality in 370 formalin-fixed
      skin biopsy specimens, showing histological features of parapsoriasis or mycosis
      fungoides. PCr products were analyzed by temperature gradient gel electrophoresis
      (TGGE). We selected 20 positive cases for use in a comparison of this technique
      with conventional agarose and polyacrylamide gel electrophoresis (PAGE). With
      TGGE the T-cells had shown monoclonality in 272 of the 370 cases; with agarose
      electrophoresis they did so in only 5 of the 20 selected cases and with PAGE in
      16. Where multiple biopsy specimens from the same patient were analyzed, PCR
      products showed identical rearrangement patterns in TGGE. TGGE is an efficient
      technique that works on routine material and can help to verify a histological
      diagnosis of cutaneous T-cell lymphoma.

PMID- 7588552
TI  - Temperature gradient gel electrophoresis for analysis of clonal evolution in non
      Hodgkin's lymphoma of the thyroid.
AB  - To analyze the transition of an autoimmune disease into a mucosa-associated
      lymphoid tissue-non-Hodgkin's lymphoma (MALT-NHL), we investigated a total of 27
      cases of clinically diagnosed autoimmune thyroiditis with lymphoid hyperplasia.
      Three cases of thyroid hyperplasia served as controls. Monoclonal B cells were
      detected by studying rearrangement patterns of the hypervariable CDR III regions
      within the immunoglobulin heavy chain gene locus and the T-cell receptor gamma
      chain gene (TCRG). We used a seminested polymerase chain reaction (PCR) to
      demonstrate immunoglobulin rearrangements and a multiplex PCR for TCRG
      rearrangements. The PCR products were analyzed by temperature gradient gel
      electrophoresis to expand mixtures of homo- and hetero-duplices within
      heterogeneous populations of B cells. With this approach we found monoclonality
      in 14 of the 27 cases of Hashimoto's disease. In a reinvestigation we discovered
      additional histological and immunohistochemical features of MALT-NHL in 17 cases.
      The 14 cases of thyroiditis with clonally expanded B cells clearly demonstrate
      the transition from autoimmune disease to non-Hodgkin's lymphoma.

PMID- 7588554
TI  - The use of genomic DNA probes for in-gel hybridization.
AB  - Hybridization within agarose gels using oligonucleotide probes has been described
      in several publications; genomic DNA probes, however, have been used rarely and
      only with limited success. Here we present a simple and convenient procedure for
      in-gel hybridization using radiolabeled genomic DNA fragments. The protocol was
      improved by the use of formamide in the hybridization as well as in the washing
      step. This method was compared with the conventional Southern blotting technique
      and was shown to produce good results in restriction pattern analysis, as well as
      in chromosomal localization with the help of pulsed field gel electrophoresis.

PMID- 7588556
TI  - Molecular characterization of Borrelia burgdorferi sensu lato strains by pulsed
      field gel electrophoresis.
AB  - The large restriction fragment patterns (LRFP) and linear plasmid profiles of
      eight tick isolates of Borrelia burgdorferi sensu lato were investigated with
      pulsed-field gel electrophoresis (PFGE). The whole cell lysate was examined with
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The MluI
      LRFP differentiates two species of Borrelia burgdorferi sensu lato (Borrelia
      burgdorferi sensu stricto and Borrelia garinii). LRFP is a suitable method to
      demonstrate genetic hetero- or homogeneity of isolates within one species without
      subsequent hybridization utilizing diverse probes. Different strains with similar
      or identical LRFP can be further discriminated by plasmid profile analysis. Our
      results show that each strain analyzed had a different plasmid profile. Therefore
      the linear plasmid profile has a potential application as a strain typing
      procedure. SDS-PAGE of whole-cell lysate supports the findings of homology within
      the B. burgdorferi sensu stricto species and the heterology within the B. garinii
      species.

PMID- 7588555
TI  - Analysis of thyroid stimulating hormone-receptor mutations by temperature
      gradient gel electrophoresis.
AB  - Somatic mutations in the genes for G-protein-coupled receptors which regulate
      intracellular levels of cyclic AMP have been found in several regions coding for
      the receptors of melanocyte-stimulating hormone, adrenaline, luteinizing hormone,
      rhodopsin and thyrotropin. The mutations found in the thyroid-stimulating hormone
      (TSH) receptor are restricted to cells of hyperfunctioning thyroid adenomas and
      other thyroid tumors. They are thought to lead to a constitutive activation of
      the receptor independent of TSH. We have developed a temperature-gradient gel
      electrophoresis (TGGE) assay starting with the amplification of a part of exon 10
      of the TSH-receptor gene to screen tissue of thyroid tumours. TGGE allows the
      detection of point mutations even if there are only a few cells with somatic
      mutations in tissue sections.

PMID- 7588557
TI  - Effective blotting of ultrathin polyacrylamide gels anchored to a solid matrix.
AB  - Ultrathin polyacrylamide gels bound on glass plates or plastic sheets cannot be
      removed from their support without destruction. Therefore electrophoretic
      transfer methods are not applicable. We have developed a fast diffusion blotting
      procedure which is very simple and does not need any equipment like blotting
      chamber or power supply. Furthermore, no special buffer solutions are required.
      The method is universally applicable to ultrathin sodium dodecyl sulfate, native
      as well as isoelectric focusing polyacrylamide gels.

PMID- 7588559
TI  - Quantification of oxidative phosphorylation enzymes after blue native
      electrophoresis and two-dimensional resolution: normal complex I protein amounts
      in Parkinson's disease conflict with reduced catalytic activities.
AB  - Blue native polyacrylamide gel electrophoresis (BN-PAGE), a method for the
      isolation of native membrane proteins from biological membranes, was adapted to
      the isolation of oxidative phosphorylation (OXPHOS) enzymes from milligram
      amounts of human tissues. Combined with Tricine-sodium dodecyl sulfate (SDS)-PAGE
      in the second dimension, the protein subunits of OXPHOS complexes could be
      analyzed and quantified. The characteristics of the technique are described and
      protocols for processing different tissues are provided. The technique was
      applied for the analysis of defects of OXPHOS complexes in Parkinson's disease. A
      significant reduction of complex V was observed in one case. Absolutely normal
      complex I protein amounts were in contrast to reduced catalytic activities of
      complex I in Parkinson's disease. This discrepancy can be explained by binding of
      endogenous complex I inhibitors or by alterations of a protein subunit not
      affecting the assemblage of the complex but modifying the enzymatic properties.

PMID- 7588558
TI  - Biotinylation: a nonradioactive method for the identification of cell surface
      antigens in immunoprecipitates.
AB  - A nonradioactive method was employed to detect different cell membrane antigens
      on human polymorphonuclear granulocytes, monocytes and platelets. We compared the
      reactivity of one monoclonal antibody, N1III10, assumed to be Fc gamma RII
      specific by functional assays, with other well-characterized monoclonal
      antibodies and human sera. Intact cells were incubated with biotin N
      hydroxysulfosuccinimide ester which preferentially reacts with lysine residues in
      polypeptides. Biotin-labeled cells were lysed and the antigen was isolated from
      the cell lysate by immunoprecipitation with the antibody bound to Protein A
      Sepharose. The precipitates were separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, transferred onto nitrocellulose membrane, and
      visualized by a streptavidin-alkaline phosphatase system with a suitable
      substrate. Using this biotin-labeling system we could show that N1III10 detects a
      40 kDa antigen on monocytes and platelets, comparable to that expected of Fc
      gamma RII monoclonal antibodies.

PMID- 7588560
TI  - Electrophoretic resolution versus fluctuations of the lateral dimensions of a
      capillary.
AB  - Because the local electrical resistance is inversely proportional to the local
      cross-section of a capillary, the intensity of the electric field varies along
      the migration path if the inner diameter of the capillary is not constant.
      Therefore, fluctuations of the lateral dimensions of a capillary can directly
      affect the net elution time as well as the peak width, and, hence the final
      resolution. In this article, we develop the theoretical framework for the study
      of such effects. We then examine the simple case where both the mobility and the
      diffusion coefficient are field-independent; in particular, we demonstrate that
      resolution can be severely reduced if the inner walls are not flat, and that
      optimal resolution is always obtained for perfectly flat walls. Generalized to
      ultrathin gels, our results clearly indicate that both random and systematic
      variations of the gel thickness can greatly affect the performance of the
      separation process. Acceptable degrees of flatness are estimated for both
      geometries. This study thus provides a quantitative understanding of the type of
      quality control one requires to obtain optimal results with capillaries and
      ultrathin gels.

PMID- 7588561
TI  - Separation and quantitation of reverse transcriptase polymerase chain reaction
      fragments of basic fibroblast growth factor by capillary electrophoresis in
      polymer networks.
AB  - In human ovarian carcinomas (epithelial and endometrial tumors) the presence of
      mRNA coding for the basic fibroblast growth factor (bFGF) was previously
      demonstrated by reverse transcription-polymerase chain reaction (PCR). For
      quantitation purposes, competitive PCR is adopted, using a competing fragment a
      sequence of a highly homologous bovine bFGF. However, separation and detection of
      the PCR products by slab gel electrophoresis and ethidium bromide staining gives
      poor quantitative data due to the nonstoichiometric binding of the dye. Thus, the
      only possible quantitation that can be obtained is via autoradiography with 32P
      labeled primers. We report here a capillary electrophoresis protocol, in 6%
      linear, liquid polyacrylamide as a sieving system, able to fully resolve and
      quantify the undigested (354 bp) bovine and the digested (295 bp and 59 bp) human
      fragments, with peak ratios in good agreement with the autoradiographic data.

PMID- 7588562
TI  - Cyclodextrin modified micellar electrokinetic chromatography for the chiral
      direct resolution of (+), (-)-trans-1,2-dihydrodiol metabolite of chrysene in
      vitro activated by rat liver microsome S9 fraction.
AB  - A gamma-cyclodextrin (gamma-CD) modified electrokinetic micellar capillary
      chromatography (MEKC) method was used for the enantiomer separation of a racemic
      trans-1,2-dihydro-1,2-dihydroxy-chrysene (chry-trans-1,2-diOH) mixture. The
      chiral resolution was strongly influenced by several important parameters:
      surfactant concentration and addition of organic modifier to the background
      electrolyte (BGE). An optimized electrophoretic system was used, consisting of
      the following conditions: 25 mM phosphate buffer, pH 7.8, 50 mM sodium dodecyl
      sulfate, 20 mM gamma-CD, 7.4% v/v 2-propanol as BGE; the applied voltage, 18 kV,
      corresponded to 37 microA at a constant temperature of 25 degrees C. This
      electrophoretic method was applied for monitoring the chry-trans-1,2-diOH
      enantiomer formation in a real sample, obtained from in vitro metabolic
      activation of chrysene by phenobarbital-beta-naphthoflavone-induced rat
      microsomes. The (+) and (-) enantiomers were identified by the racemate and the
      single enantiomer standard addition method and by spectra comparison with the
      synthetic compound. Under the experimental conditions used for chrysene
      activation, the (+) optical isomer was the prevailing form. The CD-MEKC system
      showed high reproducibility and selectivity, allowing a fast and interference
      free analysis even of the in vitro metabolic sample extract, without any
      pretreatment.

PMID- 7588563
TI  - Continuous focusing of biological particles by continuous immuno magnetic sorter:
      technique and applications.
AB  - We have developed a device for continuous deviation-mode, open-gradient
      fractionation of strongly magnetizable particles based on an electrophoresis
      counter-flow chamber. A mixture of magnetically labeled and nonlabeled particles
      can be injected into a given continuously flowing chamber buffer. The particles
      pass the inhomogeneous magnetic field of the open-gradient electromagnet in two
      narrow streams. According to the magnetic moments, induced by the magnetic field,
      magnetically labeled particles are deviated. The nonlabeled particles pass the
      magnetic field with negligible interaction. The deviated particles are focused
      into a stream that is completely separated from the streams of the nondeviated
      particles. The streams are fractionated by the counter-flow technique and
      collected in different vials. A high sorting purity, depending only on the
      specificity of the antibodies or similar labeling techniques, and a high through
      put rate of up to 10(9) particles per hour was achieved. This was experimentally
      shown both by test particles and blood cells. The vital conditions of these blood
      cells were maintained by magnetic sorting.

PMID- 7588565
TI  - Detection of platinum species in plant material.
AB  - Model experiments for the detection of platinum species in extracts from native
      and platinum-treated grass cultivations are described. The procedural steps are
      cultivation of the grass samples, extraction and concentration of the platinum
      species by ultrafiltration and freeze-drying, preparative separation of the
      species by gel chromatography followed by isotachophoresis, and sequential
      analytical detection of the separated platinum species by adsorptive voltammetry.
      After isotachophoresis, sharp peaks of platinum species could be detected. In the
      native grass extract only one platinum species (160-200 kDa) was found. In the
      platinum-treated grass extracts several platinum species were observed in the
      molecular mass range from 1 to > 1000 kDa. By an extremely sensitive platinum
      determination method (adsorptive voltammetry; detection limit, 2 pg Pt abs.) it
      was possible to detect platinum even in stained protein bands from horizontal gel
      electrophoresis of platinum containing fractions obtained after isotachophoresis.

PMID- 7588564
TI  - Biological activity of prostate-specific antigen isolated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and electroelution.
AB  - Human prostate-specific antigen (PSA), a 33 kDa kallikrein-like serine protease,
      occurring in the prostate, in seminal plasma and in blood, was prepared under
      nonreducing conditions in an enzymatically active form from seminal plasma by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by
      fast copper staining, electroelution from gel slices and dialysis against
      isotonic phosphate-buffered saline (PBS). Enzymatic activity was demonstrated for
      the first time directly by cleavage of semenogelin, one of the biological
      substrates of PSA, isolated by the same procedure, i.e. SDS-PAGE and
      electroelution, but from seminal vesicle fluid. The purified PSA formed SDS
      stable complexes with the two major extracellular protease inhibitors in blood,
      alpha 1-antichymotrypsin (alpha 1-ACH) and alpha 2-macroglobulin (alpha 2-M). PSA
      isolated under reducing conditions was enzymatically inactive and could not bind
      to the protease inhibitors alpha 1-ACH and alpha 2-M.

PMID- 7588566
TI  - Separation of jumper ant (Myrmecia pilosula) venom allergens: a novel group of
      highly basic proteins.
AB  - The sting of the jumper ant (Myrmecia pilosula) causes severe allergic reactions,
      including anaphylaxis in sensitized individuals. Two of the major allergens, Myr
      p I and Myr p II, have been cloned, immunocharacterized and nucleotide-sequenced
      and they encode 112 and 75 residue polypeptides, respectively. Both allergens are
      highly basic proteins having isoelectric point values greater than 10. However,
      electrophoretic analysis has generated conflicting results as to the actual sizes
      of the allergens in the native venom. Electrophoretic, immunological and N
      terminal analyses suggested that these allergens undergo extensive post
      translational processing to final forms of 45 and 27 residues, respectively. The
      results highlight the difficulties in the study of small, basic proteins and
      polypeptides by electrophoretic techniques.

PMID- 7588567
TI  - Detection of immunoglobulin G glycosylation changes in patients with rheumatoid
      arthritis by means of isoelectric focusing and lectin-affinoblotting.
AB  - Patients with rheumatoid arthritis have a reduced prevalence of immunoglobulin G
      (IgG) oligosaccharide chains terminating in galactose, thus exposing N
      acetylglucosamine. We analyzed IgG glycosylation in patients with rheumatoid
      arthritis, patients with early synovitis, and in controls by means of isoelectric
      focusing and lectin-affinoblotting. The ratio of N-terminal N-acetylglucosamine
      and galactose was determined using specific biotin-labeled lectins. The IgG
      glycosylation state may well be of clinical value in the differential diagnosis
      of patients presenting with early synovitis.

PMID- 7588568
TI  - Expression of the human urokinase-type plasminogen activator receptor in E. coli
      and Chinese hamster ovary cells: purification of the recombinant proteins and
      generation of polyclonal antibodies in chicken.
AB  - The receptor for urokinase-type plasminogen activator (uPAR) may contribute to
      the invasive and metastatic capacity of tumor cells by focusing the serine
      protease urokinase-type plasminogen activator (uPA) to the cell surface. uPA
      activates plasminogen to plasmin which in turn degrades extracellular matrix
      proteins or activates other proteases. Mature uPAR is a heavily glycosylated
      protein of about 284 amino acids attached to the plasma membrane via a glycosyl
      phosphatidylinositol (GPI) anchor. A set of different polyclonal uPAR antibodies
      has been generated in order to investigate the role of uPAR in tumor spreading in
      more detail. For this purpose, uPAR (lacking the GPI anchor) was expressed in E.
      coli and Chinese hamster ovary (CHO) cells. Recombinant uPAR from E. coli
      (corresponding to amino acids 1-284 of human uPAR) was expressed with an N
      terminal histidine-tag insertion and purified by nickel chelate affinity
      chromatography. Soluble uPAR, synthesized by CHO cells (corresponding to amino
      acids 1-277 of human uPAR), was isolated by ligand (uPA) affinity chromatography.
      Expression in E. coli led to a nonglycosylated form of uPAR, whereas uPAR
      produced by CHO cells seemed to be glycosylated to a similar extent as the
      naturally occurring human form of uPAR (as analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis). Prior to immunization the N-termini of the
      recombinant uPAR variants were determined by amino acid sequence analysis.
      Polyclonal antibodies were generated in chickens and purified from egg yolk. The
      reaction patterns of these antibodies were analyzed by Western blot analyses and
      flow cytofluorometry.

PMID- 7588570
TI  - Differentiation of scombroid fish species (tunas, bonitos and mackerels) by
      isoelectric focusing, titration curve analysis and native polyacrylamide gel
      electrophoresis of sarcoplasmic proteins.
AB  - Differentiation of scombroid fishes was possible by electrophoresis of
      sarcoplasmic proteins using either isoelectric focusing (IEF), titration curve
      analysis, or native polyacrylamide gel electrophoresis (PAGE). By IEF with Phast
      Gels 3-9 species specific patterns, characterized by a few bands in the cathodal
      part of the gels, were obtained. This type of gel was also used for titration
      curve analysis. Here, too, the closely related species Thunnus thynnus and T.
      albacares gave different protein patterns. Native PAGE, native cathodal
      electrophoresis in Clean Gel 10% with buffer pH 5.5, proved to be a fast and
      simple method for differentiation of scombroid fishes. As most of the prominent
      sarcoplasmic proteins of these species have pIs in the neutral or alkaline pH
      range, they are positively charged at pH 5.5 and move to the cathode.

PMID- 7588571
TI  - A novel strategy to identify maternal and paternal inheritance in the mouse.
AB  - A novel strategy for identifying proteins which reveal maternal or paternal
      inheritance in the mouse is presented. Using two-dimensional electrophoresis we
      investigated protein expression patterns of adult liver and different embryonic
      and extraembryonic tissue in C57BL/6Crl and in DBA/2Crl mice, as well as in their
      reciprocal hybrids. We found three groups of protein spots which showed maternal
      or paternal inheritance of quantitative variations. These proteins were
      characterized by N-terminal or internal amino acid sequencing, by determination
      of the amino acid composition, by glycoprotein staining and RNA expression
      analysis. The three proteins identified were: alpha-enolase, cyclophilin and beta
      group hemoglobins. The parental effects observed for alpha-enolase and
      cyclophilin were found to be due to parent-specific post-translational
      modifications of these proteins. For the beta-group hemoglobins our results
      suggested parental effects on the transcriptional level.

PMID- 7588572
TI  - The further construction of the two-dimensional database of common human
      proteins.
AB  - The master two-dimensional gel database (D. Burggraf et al., Electrophoresis
      1992, 13, 729-732) [1] of common human proteins has been expanded to include
      detailed protein characteristics. Human cellular proteins from 5 cell lines and
      different cell organelles representing various tissues (muscle, nervous,
      connective, epithelial blood) and germ layers (ectoderm, endoderm and mesoderm),
      were separated by two-dimensional gel electrophoresis (2-DE). According to a
      recently developed algorithm, master gels of these different cells were
      established by computer-aided image processing. An expanded map with protein
      chemical information of the polypeptides common to all human cells is shown. The
      synthetic, common human protein-map represents 856 spots resolved with an
      accuracy of 4 cm/pI unit. The protein spots were characterized either by their
      isoelectric point, molecular mass, integrated intensity, background-corrected
      optical density, spot area, or cellular distribution. About 80 proteins were
      further characterized and identified by protein name, amino acid composition
      analysis, N-terminal sequencing, enzymatic digest and subsequent peptide
      sequencing. Additionally the proteins of the common human protein map were
      identified by Western blotting. Specific information regarding glycosylation and
      quantitation of expression levels after chemical, biological and mechanical
      stimulation is included in the database.

PMID- 7588569
TI  - Mineral-bound noncollagenous proteins in archaeological human skeletons.
AB  - Archaeometric approaches to archaelogical human bone also include the extraction,
      identification and molecular analysis of surviving bone proteins. Due to its
      abundance as a matrix protein, most studies focus on collagen (e.g. radiocarbon
      dating). Also, a variety of serum proteins are detectable in excavated skeletons.
      Very limited knowledge still exists on mineral-bound noncollagenous bone proteins
      from ancient bones because, in the mature tissue, they occur in trace amounts
      only. Moreover, post-mortem decomposition is likely to change characteristic
      features of the molecules. Due to their suggested role as growth and
      developmental factors, identification and quantification of such proteins should
      be valuable for both physical anthropology and epidemiology. We present a valid
      method for the detection of small amounts of surviving mineral-bound
      noncollagenous proteins in excavated human bones up to 7500 years of age.

PMID- 7588574
TI  - Two-dimensional gel electrophoresis and immunoblotting of human serum albumin
      modified by reaction with penicillins.
AB  - A two-dimensional gel electrophoresis and immunoblotting procedure has been
      developed to assess the level of modification by penicillins in human serum
      albumin. The procedure can be used in in vitro experiments and in clinical
      studies with sera from patients treated with penicillins.

PMID- 7588573
TI  - Chamber-specific expression of human myocardial proteins detected by two
      dimensional gel electrophoresis.
AB  - High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE),
      followed by computer-assisted image analysis (PDQUEST) was used to screen atrial
      and ventricular protein patterns for quantitative and qualitative differences in
      protein expression. Myocardial proteins from left ventricular (LV) and right
      atrial (RA) samples from end-stage, failing explanted hearts and from a healthy
      donor heart (control) were separated by 2-D large gel electrophoresis. Ten RA
      versus ten LV gels from explanted dilated cardiomyopathic (DCM) hearts were
      analyzed for quantitative differences in their spot patterns. Of the 197 spots
      matched to every gel, 40 spots differed significantly in intensity between RA and
      LV for DCM patients. A larger number of atrial and ventricular gels (20 RA, 20
      LV) from DCM patients and from a healthy donor heart (4 RA, 4 LV gels) were
      analyzed for qualitative differences in protein expression. Three protein spots
      (SSP 1120: M(r)/pI:20.5 kDa/4.6; SSP 1119: M(r)/pI:20.6 kDa/4.5; SSP
      0117:M(r)/pI:20.7/ < 4.5) that are present in all RA gels for DCM patients are
      absent in all LV gels. Two protein spots (SSP 0112: M(r)/pI:17.2 kDa,/ < 4.4; SSP
      0114:M(r)/pI:17.6 kDa/ < 4.4) occur only in all LV gels but not in the RA gels.
      These five qualitatively differing spots are identical in DCM patients and in the
      healthy donor heart. Some of the differing spots were internally sequenced and
      identified as myosin light chain isoforms (myosin light chain 2, atrial; myosin
      light chain 2, ventricular; myosin light chain 1, atrial) with the Protein
      Identification Resource (PIR) accession numbers A44451, S03708, A30881,
      respectively. Additionally, phosphoglycerate mutase (PIR: JQ0750) and ATP
      synthase alpha chain (PIR: S17193) were identified. Thus, quantitative and
      qualitative differences between atrial and ventricular protein patterns were
      identified by 2-D PAGE. A characteristic distribution of myosin light chains
      between atrial and ventricular human myocardium was found using our approach.

PMID- 7588575
TI  - Phosphorylation of ribosomal protein L30 after herpes simplex virus type 1
      infection.
AB  - In addition to an irreversible stimulation of S6 ribosomal protein
      phosphorylation, there is a modification of a subset of ribosomal proteins by
      phosphorylation after herpes simplex virus type 1 (HSV-1) infection. Moreover, in
      the course of this infection, three additional phosphorylated proteins can be
      extracted from ribosomes and separated by two-dimensional electrophoresis (2-DE)
      of total ribosomal proteins. One of them exhibits an identical molecular mass to
      L30, while being more acidic. This protein is phosphorylated on serine residues.
      The kinetics of appearance of this protein in the ribosomal fraction correlated
      with a decrease in L30 staining, as shown by 2-DE. Determination of the N
      terminal amino acid sequence of this extra phosphoprotein and of L30-derived
      peptides demonstrated the identity of these two proteins.

PMID- 7588576
TI  - Association of protein polymorphism among pepper (Capsicum annuum L.) inbred
      lines with agronomic performance of their crosses.
AB  - The genetic variation of 10 morphologically similar pepper (Capsicum annuum L.)
      inbred lines has been analyzed by two-dimensional electrophoresis with
      immobilized pH gradient (IPG-DALT) of seed proteins. For all pairs of inbred
      lines genetic distance indices were calculated on the basis of the IPG-DALT
      analysis and a genetic tree was constructed. The protein polymorphism data of the
      10 inbred lines were integrated into a pepper breeding program to validate the
      assumption that there is a higher chance of achieving better hybrid performance
      when the genetic distance between the parents is as great as possible. Field
      trials were performed in Turkey and consisted of a total of 27 crossings based on
      9 inbred lines. Fifteen hybrids exceeded the crop yield of the better parent and
      8 additional hybrids exceeded the mean crop yield of both parents. The genetic
      distance indices of the parental inbred lines based on protein polymorphism data
      were not significantly correlated to heterosis performance of the experimental
      hybrids (r = 0.20), indicating that protein polymorphism data add little to the
      prediction of single cross hybrid performance. Nevertheless, protein polymorphism
      data support the breeder in being more effective in finding out the best inbred
      combinations, because most of the less promising crossings can be omitted from
      the expensive and time-consuming performance tests. Those hybrids whose distance
      indices exceeded the mean of all 27 distance values (0.52) were superior to the
      mean value of all heterosis performances by 19%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588577
TI  - Forensics on wild animals: differentiation between otter and pheasant blood using
      electrophoretic methods.
AB  - Electrophoretic techniques were used to prove illegal hunting of a protected
      species as small amounts of dried blood stains could be clearly identified as of
      otter origin. Species differentiation between the otter (Lutra lutra) and
      pheasant (Phasianus colchicus) was based mainly on small differences in
      electrophoretic mobilities of the respective albumins and hemoglobins in one
      dimensional separations. Additional differences in minor proteins of the two
      species were revealed by two-dimensional electrophoresis. Electrophoresis thus
      also proved to be a valuable tool for forensic purposes.

PMID- 7588580
TI  - Effects of mild hypoxia on perceptual-motor performance: a signal-detection
      approach.
AB  - Twelve healthy male subjects were required to make speeded judgements concerning
      the orientation of visual stimuli while breathing air at reduced partial pressure
      in a hypobaric chamber at altitudes of 7000 and 12,000 ft. A control condition
      was also conducted at sea level, and subjects received practice on the task at
      sea level prior to the commencement of the experiment. Significantly slower
      response times were obtained at 7000 and 12,000 ft relative to sea level. A
      signal-detection analysis showed that accuracy of judgement was significantly
      poorer at 12,000 ft, but oxygen deprivation has no systematic effect on response
      criterion.

PMID- 7588581
TI  - Mechanical loading on the low back in three methods of refuse collecting.
AB  - The mechanical loading on the low back was studied in three different current
      methods of refuse collecting: in polythene bags, two-wheeled mini-containers and
      large four-wheeled containers. To this end the most prominent activities of each
      collecting method were performed in a laboratory. On the basis of movement
      analysis, force measurements and biomechanical modelling, spinal compressive and
      shear forces were estimated. From these forces and from the frequency of
      activities during the working day (assessed in a preliminary field study) the low
      back stress in each collecting method was evaluated. In the bag-method, peak
      forces when throwing the bags ranged from 3341 to 5179 N (average compression)
      and from 284 to 673 N (shear) among the different conditions studied. The act of
      picking up bags also showed rather high forces (exceeding the NIOSH limit for
      disc compression in most cases). The frequency of exposure to these forces in the
      field is rather high (workers pick up and throw on average 807 times each day).
      The mini-container method compares favourably to the bags method. Peak
      compressive and shear force in tilting/pushing and pulling mini-containers ranged
      from 1657 to 2654 N and from 123 to 248 N respectively. Also, the frequency of
      stressful events in the field is lower in this method. In the large container
      method extremely high peak forces (e.g. compression ranged from 4991 to 5810 N)
      were observed in the task of putting the empty container back from street level
      to sidewalk level (surmounting the kerb). The frequency of activities like
      pushing, pulling and lifting the large container in the field is much lower
      compared with activities in the other methods. On the basis of the frequency and
      magnitude of spinal forces it was concluded that the mini-containers should be
      preferred to the bags. If kerbs are removed at container places and tasks are
      performed by two instead of a single person, the large container method would
      form another good alternative to the stressful task of collecting refuse in bags.

PMID- 7588579
TI  - Detection of nonfunctional overexpression gene products using two-dimensional gel
      electrophoresis with a narrowed pH range.
AB  - A commonly used technique in the analysis of yeast protein function is the
      overexpression of cloned genes. In the case that overexpression does not lead to
      an altered phenotype a stable synthesis of the protein has to be demonstrated.
      Here an example is shown where overexpression of the yeast HYP2 genes, coding for
      a hypusine-containing protein, was alternatively analyzed by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) alone or by two-dimensional
      (2-D) gel electrophoresis, using the narrowed pH range of 4.5-5.4. The results of
      the SDS-PAGE suggested a stable overproduction of HYP gene product, whereas 2-D
      analysis revealed an accumulation of nonfunctional protein isoforms.

PMID- 7588578
TI  - Studies on the carbohydrate moieties of the timothy grass pollen allergen Phl p
      I.
AB  - Timothy grass pollen was investigated in order to determine the carbohydrate
      moieties of its major grass group I (Phl p I) and to study its impact on
      allergenicity. Based on computer calculations one N-glycosylation site was
      deduced from the cDNA data of Phl p I. After two-dimensional polyacrylamide gel
      electrophoresis, followed by blotting of pollen extract and by use of the
      monoclonal antibody IG 12 we identified at least six isoallergens of Phl p I with
      the main spots at a molecular mass of 35-37 kDa and a pI range of 6.5-7.3.
      Deglycosylation by trifluoromethanesulfonic acid resulted in a decrease of about
      2 kDa. Treatment with N-glycosidase A resulted in a partial deglycosylation,
      while N-glycosidase F and O-glycosidase had no effect. Ten lectins were
      investigated for their binding to Phl p I components: Aleuria aurantia agglutinin
      showed strong reactivity (indicating fucose residues), while Galanthus nivalis
      agglutinin (indicating mannose residues) and concanavalin A (indicating mannose,
      glucose or N-acetylglucosamine residues) showed weak binding. By neutral sugar
      analysis we determined similar contents of the monosaccharides in the
      isoallergens. In order to study the influence of the carbohydrate structures of
      Phl p I on IgE reactivity we tested some patient sera for their reactivity with
      intact and deglycosylated Phl p I. Even though most of the IgE antibodies bind at
      the protein core, we detected one serum that recognized carbohydrate moieties on
      the Phl p I.

PMID- 7588582
TI  - An analysis of scanning postures among grocery cashiers and its relationship to
      checkstand design.
AB  - Mounting evidence suggests that musculoskeletal disorders are prevalent among US
      retail food workers. Cashiers who use electronic scanners appear to be at
      especially high risk for upper extremity musculoskeletal disorders. Checkstand
      design has been implicated as a contributor to musculoskeletal injury among
      cashiers because workstation design can significantly impact working posture. The
      present study examines working posture among two groups of cashiers to determine
      if checkstand design is associated with substantial differences in posture and
      movement during scanning. The work activities of twenty grocery cashiers using
      one of two checkstand designs (front-facing and right-hand takeaway) were
      examined. Videotapes of cashiers performing scanning tasks were observed and
      associated postures and movements were visually coded. The right-hand takeaway
      design was associated with a significantly higher percentage of non-neutral trunk
      postures than the front-facing design. However, there were no significant
      differences in shoulder posture, grasp, or scanning motion associated with
      checkstand/scanner design. Factors that appeared to affect cashier work posture
      during scanning included stature, order size, and product type. Although
      improving the checkstand design may reduce the occurrence of certain awkward
      postures and static muscle loading conditions among cashiers, the success of
      these interventions is likely to be limited unless follow-up programmes are
      instituted to ensure that cashiers are able to use these designs effectively.
      Furthermore, fundamental changes in cashier work may be required to fully
      eliminate hazards for musculoskeletal disorders from this job.

PMID- 7588583
TI  - Predicting the discomfort caused by tractor vibration.
AB  - A field study was conducted to investigate how the discomfort caused by the
      vibration of an agricultural tractor can be predicted from objective measurements
      of the vibration in the cabin. Eleven professional drivers judged the vibration
      discomfort produced by four different tractors on sixteen different test runs. At
      the same time, for all the tests, the multi-axis vibration in the cabin was
      measured on the floor, the seat pan and the seat backrest. For each of the 704
      tests carried out, the discomfort caused by the vibration was predicted from the
      measured vibration in the cabin using a total of twenty different analysis
      procedures. The relative merits of the different prediction procedures were
      investigated by comparing, on an individual basis for each driver/tractor
      combination, the statistical significance of the correlations between the
      subjective judgements and the predicted values. There was considerable
      variability in the drivers' subjective responses, but it was concluded that,
      overall, the best procedure for predicting the vibration discomfort in an
      agricultural tractor is that recommended by ISO 2631 (International Organization
      for Standardization 1978), using the frequency weighted rms values of the
      vibration (0.5-20 Hz) measured on the seat pan in the three orthogonal
      directions, and taking the square-root-of-the-sum-of-the-squares of the values in
      order to combine the directions as recommended in Amendment 1 to ISO 2631
      (International Organization for Standardization 1982).

PMID- 7588584
TI  - Isodynamic evaluation of trunk muscles and low-back pain among workers in a steel
      factory.
AB  - A cross-sectional study was conducted to explore the relationship between dynamic
      parameters of trunk muscle strength and the occurrence of low-back pain (LBP).
      Isodynamic strength measurements were performed among 31 male maintenance workers
      with spells of low-back pain in the past 12 months and 28 maintenance workers
      without a history of low-back pain. In general, workers with low-back pain showed
      a lower trunk muscle performance than the workers without low-back pain. Only the
      measures of torque during lateral movement differed significantly between both
      groups. Regression analysis revealed the importance of the nature of low-back
      pain for trunk muscle strength. Most parameters of trunk muscle strength were
      significantly decreased among workers with chronic low-back pain of a rather
      severe nature, showing reductions from 18% to 50%. None of the work-related risk
      factors for low-back pain contributed significantly to the prediction of trunk
      strength measures. The study suggests that isodynamic evaluation of trunk muscle
      strength may assist in determining objective measures for the severity of low
      back pain rather than in evaluating a subject's capability of successfully coping
      with a specific work load.

PMID- 7588586
TI  - Further characterization of kindling antagonism.
AB  - Alternating stimulation of two sites in the forebrain culminates in typical
      kindling of generalized seizures from one site (dominant), whereas the other site
      (suppressed) supports only nongeneralized seizures for as long as stimulation of
      the dominant site continues, a phenomenon referred to as kindling antagonism.
      With the termination of stimulation of the dominant site, however, seizures
      provoked from the suppressed site eventually generalize, a progression thought to
      reflect the resumption of kindling from a previous point of arrest. To further
      assess the nature of kindling antagonism, we established antagonism between the
      amygdala and the septal area and subsequently evaluated the development of
      seizures provoked by stimulation of sites distal to the dominant site (always the
      amygdala). In Experiment 1, a 30-d stimulation-free period imposed after the
      establishment of antagonism failed to result in immediate generalization of
      seizures provoked from the suppressed site (septal area) in seven of eight rats.
      Although these results suggest that antagonism reflects an actual arrest of
      kindling rather than a transient inhibition of seizures, they are not entirely
      unambiguous: Rats exposed to the prolonged stimulation-free period required only
      half the number of septal stimulations for the expression of a generalized
      seizure as compared to rats receiving septal stimulation immediately after the
      establishment of antagonism. The latter finding is suggestive of a transient
      component of antagonism. In Experiment 2, development of generalized seizures
      from the previously naive right amygdala was virtually identical in rats
      previously kindled from the left amygdala and in rats expressing antagonism
      between the septal area and left amygdala. Development of generalized seizures
      from the right amygdala was faster than from the left amygdala in both groups of
      rats, however, suggesting that the expression of seizures provoked from the
      suppressed site after the establishment of antagonism does not involve a general
      impairment or enhancement of transfer. Experiment 3 revealed that radio-frequency
      lesions of the dominant site (amygdala) after the establishment of antagonism did
      not alter the subsequent development of generalized seizures from the suppressed
      site (septal area). This suggests that the expression of generalized seizures
      from the suppressed site after the establishment of kindling antagonism is not
      dictated by the functional state of the dominant site.

PMID- 7588587
TI  - Impact of epilepsy on employment status: findings from a UK study of people with
      well-controlled epilepsy.
AB  - This paper examines the current employment status and recent employment history
      of 494 individuals with epilepsy whose seizures were well-controlled or in
      remission. Information about employment status and history was obtained by means
      of self-completion questionnaires, sent to eligible subjects by post. The
      sampling frame from which subjects were recruited were neurology out-patient
      departments across the UK. The majority of subjects had epilepsy in remission:
      only 15% had had a seizure in the last year and only 25% reported one in the last
      two years. A high proportion of respondents were currently in employment. Of
      those who were not, few attributed this to their epilepsy; nor did epilepsy seem
      to have a significant impact on recent employment history. In spite of the lack
      of evidence of any actual discrimination, a third of respondents nevertheless
      felt their condition affected their ability to obtain employment. The findings
      from earlier studies of high unemployment rates partly reflect bias in the
      samples studied. Our data provide evidence that where seizures are well
      controlled and uncomplicated by other handicap, people with epilepsy do not
      generally experience problems with employment.

PMID- 7588588
TI  - The pathophysiologic relationships between lesion pathology, intracranial ictal
      EEG onsets, and hippocampal neuron losses in temporal lobe epilepsy.
AB  - In temporal lobe epilepsy (TLE) lesion patients the pathology, location of
      intracranial ictal EEG onsets, and hippocampal neuron losses were compared.
      Patients (n = 63) were classified into: (1) Tumors (n = 26, e.g. astrocytomas,
      gangliogliomas); (2) vascular (n = 9, e.g. cavernous and venous angiomas); (3)
      developmental (n = 17, e.g. cortical dysplasia, heterotopias); or (4) atrophic (n
      = 11, e.g. cortical or white matter encephalomalacia). Other variables were; (1)
      the location of the temporal lesion in the mesial to lateral, and anterior to
      posterior plane, (2) a clinical history of an initial precipitating injury (IPI)
      prior to the onset of TLE (e.g. prolonged first seizure, head trauma), (3)
      hippocampal neuron densities, (4) focal or regional location by intracranial
      depth EEG of ictal onsets, and (5) seizure outcomes. Results showed that severe
      hippocampal neuron losses were associated with two statistically significant
      findings. First, patients with mesial lesions in or adjacent to the body of the
      hippocampus had greater neuron losses compared to mesial lesions anterior or
      posterior to the hippocampus (P = 0.04). Second, lesion patients with an IPI
      history had greater Ammon's horn (AH) neuron losses compared to those without IPI
      histories (P = 0.0005), and the profile of loss was similar to hippocampal
      sclerosis (HS). Granule cell losses correlated in a complex manner in that; 1) by
      regression analysis densities decreased with longer intervals of TLE (P = 0.006),
      (2) tumor patients with IPIs had less granule cell loss compared to those without
      IPIs intervals of TLE (P = 0.006), (2) tumor patients with IPIs had less granule
      cell loss compared to those without IPIs (P = 0.05), and (3) developmental
      patients with IPIs had greater granule cell loss than patients without IPIs (P =
      0.009). Mesial-temporal depth EEG electrodes were the first areas of ictal
      activity in 15 of 16 patients (94%), and greater hippocampal neuron losses were
      not associated with focal mesial-temporal EEG onsets. Seizure outcomes were worse
      in tumor patients compared to HS patients (P = 0.01), and patients with post
      resection seizures had incomplete resections of their lesions and/or hippocampi.
      These results indicate that in TLE lesion patients the amount and pattern of
      hippocampal neuron loss depends on the location of the lesion, the pathologic
      classification, and a history of an IPI. Further, despite variable neuron losses,
      in temporal lesion patients the hippocampus was nearly always involved in the
      genesis or propagation of the chronic seizures.

PMID- 7588585
TI  - The effect of amygdaloid kindling on heart period and heart period variability.
AB  - Two studies were conducted on rats to assess the effects of amygdaloid kindling
      on baseline measures of heart period and heart period variance. The results
      indicate that seizure activity was associated with increased vagal influence on
      heart period marked by sinus bradycardia and decreased beat-to-beat variability.
      The resultant bradycardia was enhanced following each seizure and persisted for
      at least a one-week period of time. The results are discussed in terms of the
      role of vagal tone in influencing abnormal cardiac patterns which could result in
      sudden unexplained death in some epileptic patients.

PMID- 7588589
TI  - Anticonvulsant therapy in the elderly--a need for placebo controlled trials.
AB  - Epileptic seizures are common in the elderly, yet data concerning the long-term
      clinical course and apparent impact of anticonvulsant therapy are scant. We
      studied 73 consecutive elderly patients with a diagnosis of seizures [remote
      symptomatic (52%), acute symptomatic (23%), progressive symptomatic (10%),
      cryptogenic (15%)] during a median period of clinical review of 33 (range 3-72)
      months. Sixty-seven patients received anticonvulsant drugs, 38 phenytoin (PHT),
      21 carbamazepine (CBZ), 6 sodium valproate (VPA) and 2 phenobarbitone. Six
      patients were untreated with drugs and three of these had no further seizures
      over a median review period of 26 months. Forty-one (61%) treated patients
      remained seizure free and a further nine patients suffered less than three fits
      per year. Seventeen patients had poorer control (three to five seizures per year
      in six patients and more than five seizures per year in eleven patients). Mean
      daily dosage of anticonvulsants (PHT 248 mg, CBZ 320 mg, VPA 571 mg) and serum
      concentrations were modest. Anticonvulsant side effects were reported by 27% of
      all treated patients (22% of those who were seizure free). Both adverse effects
      and satisfactory seizure control were associated in the majority of patients with
      serum anticonvulsant concentrations at the lower limit or below recommended
      therapeutic ranges utilised in the young. This study suggests that placebo
      controlled studies are warranted to appraise the extent to which anticonvulsant
      drugs modify a generally favourable prognosis for seizure disorders in the
      elderly and to adequately define the benefit-risk ratio of such drugs.

PMID- 7588590
TI  - Optimised interictal HMPAO-SPECT in the evaluation of partial epilepsies.
AB  - Interictal blood flow single photon emission computed tomography (SPECT) has been
      considered to be of limited value in the investigation of patients with partial
      epilepsies. Newer SPECT technologies using brain dedicated multiple detector
      systems have not been fully evaluated. To study the usefulness of an optimized
      SPECT technique, we scanned 40 epilepsy patients and ten normal subjects.
      Interictal [99mTc]hexamethylpropylene amine oxime (HMPAO) SPECT scans were
      acquired using the GE/CGR Neurocam triple-headed brain-dedicated system. The
      results of a qualitative analysis of the scans were compared to EEG and optimised
      MRI findings. Eight of the normal subjects and one of 40 patients had normal
      SPECT scans. There was a comparable concordance of lateralization between SPECT,
      MRI and EEG. The majority of our patients had mesial temporal pathology on MRI.
      Perfusion abnormalities extending beyond the mesial temporal area were common and
      did not simply relate to structural abnormalities. Quantification of blood flow
      in multiple brain regions revealed that hypoperfusion did not occur at random.
      Perfusion in the mesial temporal lobe was related to perfusion in anatomically
      and functionally related ipsilateral and contralateral brain regions. These
      hypoperfused areas probably reflect dysfunctioning areas which are related to the
      epileptogenic process.

PMID- 7588591
TI  - Effects of chronic tiagabine treatment on [3H]GABAA, [3H]GABAB and [3H]tiagabine
      binding to sections from mice brain.
AB  - (R)-N-(4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl)nipecotic acid (tiagabine) is a
      potent inhibitor of gamma-aminobutyric acid (GABA) uptake, which maintains its
      initial anticonvulsant effects when administered to mice for a prolonged period
      (21 days). In the present study, mice received chronic (21 days) p.o.
      administration of tiagabine (15 mg/kg, twice daily) or vehicle alone and the
      densities of GABAA and GABAB receptors and of [3H]tiagabine recognition sites
      were measured in several brain regions. The following changes were observed
      following chronic administration of tiagabine as compared to vehicle: significant
      reduction (18-37%) in [3H]tiagabine binding in the temporal and entorhinal cortex
      and in the molecular and granular layer of the cerebellar cortex; increases in
      the number of GABAA sites (22-44%) in various regions of the frontal cortex, in
      caudate putamen and in the lateral septum; decreases in the numbers of GABAB
      sites (18-42%) in the motor cortex, the more dorsal parts of cortex, the
      anteroventral thalamic nucleus, medial geniculate, superior colliculus and the
      molecular layer of the cerebellar cortex. Such data suggest that the GABAergic
      system is differentially modulated in a regional specific manner in response to
      chronic elevation of the extracellular levels of GABA. The significance of these
      findings in relation to the reported lack of development of tolerance to the
      anticonvulsant effects of tiagabine is discussed.

PMID- 7588593
TI  - Plasticity of AMPA and NMDA receptor-mediated epileptiform activity in a chronic
      model of temporal lobe epilepsy.
AB  - We have investigated the consequences of tetanic stimulation on epileptiform
      activity mediated by NMDA and AMPA receptors in an experimental model of human
      temporal lobe epilepsy. Recordings were performed in the CA1 area of the
      hippocampus one week following intracerebroventricular injection of kainic acid.
      Data presented here show that, after tetanic stimulation, there was a long-term
      increase in the amplitude of the population spikes associated with the
      epileptiform burst. This activity was triggered by the simultaneous activation of
      both NMDA and AMPA receptors. However, whilst the pharmacologically isolated AMPA
      component of this burst underwent long-term enhancement, the NMDA component
      underwent a long-term decrease in amplitude. These data suggest that in this
      chronic model of epileptiform activity, there is long-term potentiation of
      excitatory mediated events regulated primarily by AMPA receptors. Furthermore,
      the slow time course of the NMDA receptor-mediated synaptic conductances was
      responsible for prolonging the duration of the epileptiform bursts. However, the
      powerful depression of NMDA receptor-mediated events following tetanic
      stimulation suppressed the normally large potentiation of the overall response.
      Thus although it has been suggested that the NMDA receptor-mediated synaptic
      events contribute to the epileptogenic properties of the neocortex and
      hippocampus, this evoked depression may act as an intrinsic anticonvulsant
      mechanism.

PMID- 7588592
TI  - Effects of the GABA-uptake inhibitor tiagabine on electroencephalogram, spike
      wave discharges and behaviour of rats.
AB  - Effects of the anticonvulsant tiagabine in doses of 1, 3 and 10 mg/kg were
      investigated on electroencephalogram (EEG), spike-wave discharges and behaviour
      of WAG/Rij rats. These rats are considered as an animal model of generalized, non
      convulsive, absence epilepsy. WAG/Rij rats spontaneously show a considerable
      number of spike-wave discharges in their EEG. These discharges can be facilitated
      by GABA agonists. The facilitatory effects of these agonists are completely
      opposite to their effects on convulsive seizures, which are reduced by these
      drugs. Tiagabine enhances the effects on the GABA system, since it acts as a GABA
      re-uptake inhibitor. According to expectations, tiagabine enhanced in a dose
      related way both the number and mean duration of spike-wave discharges. The low
      dose of 1 mg/kg had almost no effects, but doses of 3 and 10 mg/kg were
      effective. Furthermore, tiagabine in the latter two doses increased the power in
      the higher beta band of the background EEG, whereas no significant changes in
      behavioural parameters were found. An unexpected finding was the occurrence of a
      second type of spike-wave discharges. These were again seen with the two higher
      doses of tiagabine, while 1 mg/kg had no effect. An assumption is that this
      second type of discharges are forerunners of genuine spike-wave discharges. In
      general, this experiment supports that non-convulsive epilepsy is associated with
      a GABA hyperfunction. It also underlines the biochemical differences of
      convulsive and non-convulsive animal models of epilepsy. Tiagabine, with its GABA
      mimetic properties, belongs to the category of drugs effective in convulsive
      animal models and not in non-convulsive models of epilepsy.

PMID- 7588594
TI  - Altered T cell development in mice with a targeted mutation of the CD3-epsilon
      gene.
AB  - To determine which CD3 components are required for early T cell development, we
      generated mice with a targeted mutation of the CD3-epsilon gene and characterized
      their T cell populations relative to those found in CD3-zeta/eta-and recombinase
      activating gene (RAG)-deficient mice. In the absence of intact CD3-epsilon
      subunit, thymocytes do not progress beyond the CD44-/lowCD25+ triple-negative
      stage and appear to be arrested at the very same developmental control point as
      RAG-deficient thymocytes. In contrast, the disruption of the CD3-epsilon/eta gene
      does not totally abrogate the progression through this control point. CD3-epsilon
      deficient thymocytes do rearrange their T cell receptor (TCR) beta gene segments
      and produce low levels of full-length TCR beta transcripts. Taken together, these
      results establish an essential role for the CD3-epsilon gene products during T
      cell development and further suggest that the CD3-epsilon polypeptides start to
      exert their function as part of a pre-TCR through which CD44-/lowCD25+ triple
      negative cells monitor the occurrence of productive TCR beta gene rearrangements.
      Finally, the absence of intact CD3-epsilon polypeptides had no discernible effect
      on the completion of TCR gamma and TCR delta gene rearrangements, emphasizing
      that they are probably not subjected to the same epigenetic controls as those
      operating on the expression of TCR alpha and beta genes.

PMID- 7588597
TI  - Structure of the binding site for inositol phosphates in a PH domain.
AB  - Phosphatidylinositol bisphosphate has been found to bind specifically to
      pleckstrin homology (PH) domains that are commonly present in signalling proteins
      but also found in cytoskeleton. We have studied the complexes of the beta
      spectrin PH domain and soluble inositol phosphates using both circular dichroism
      and nuclear magnetic resonance spectroscopy, and X-ray crystallography. The
      specific binding site is located in the centre of a positively charged surface
      patch of the domain. The presence of 4,5-bisphosphate group on the inositol ring
      is critical for binding. In the crystal structure that has been determined at 2.0
      A resolution, inositol-1,4,5-trisphosphate is bound with salt bridges and
      hydrogen bonds through these phosphate groups whereas the 1-phosphate group is
      mostly solvent-exposed and the inositol ring has virtually no interactions with
      the protein. We propose a model in which PH domains are involved in reversible
      anchoring of proteins to membranes via their specific binding to
      phosphoinositides. They could also participate in a response to a second
      messenger such as inositol trisphosphate, organizing cross-roads in cellular
      signalling.

PMID- 7588595
TI  - Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153).
AB  - Adipocytic conversion of 3T3-L1 cells is dependent on induction of transcription
      factors from the C/EBP family that activate promoters of adipogenic genes. We
      find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP
      isoforms alpha and beta and directs the resulting heterodimer away from classic
      C/EBP-binding sites, markedly inhibits this differentiation process.
      Surprisingly, the presence of CHOP early in the differentiation process inhibits
      C/EBP alpha and beta gene expression. Ectopic expression of C/EBP alpha bypasses
      the inhibitory effect of CHOP on differentiation, providing further evidence that
      CHOP action is mediated by inhibition of C/EBP alpha gene expression rather than
      merely inhibiting the encoded protein's DNA-binding activity. A similar pattern
      of attenuated expression of C/EBP alpha and beta is also observed in cells
      induced to differentiate in media with low glucose concentration. This stressed
      culture condition is associated with induction of endogenous CHOP and marked
      attenuation of the differentiation process. Our data suggest that CHOP functions
      as an inducible inhibitor of adipocytic differentiation in response to metabolic
      stress. It does so by interfering with the accumulation of adipogenic C/EBP
      isoforms.

PMID- 7588596
TI  - WT1 suppresses synthesis of the epidermal growth factor receptor and induces
      apoptosis.
AB  - The Wilms tumor suppressor gene WT1 encodes a developmentally regulated
      transcription factor that is mutated in a subset of embryonal tumors. To test its
      functional properties, we developed osteosarcoma cell lines expressing WT1 under
      an inducible tetracycline-regulated promoter. Induction of WT1 resulted in
      programmed cell death. This effect, which was differentially mediated by the
      alternative splicing variants of WT1, was independent of p53. WT1-mediated
      apoptosis was associated with reduced synthesis of the epidermal growth factor
      receptor (EGFR), but not of other postulated WT1-target genes, and it was
      abrogated by constitutive expression of EGFR. WT1 repressed transcription from
      the EGFR promoter, binding to two TC-rich repeat sequences. In the developing
      kidney, EGFR expression in renal precursor cells declined with the onset of WT1
      expression. Repression of EGFR and induction of apoptosis by mechanism that may
      contribute to its critical role in normal kidney development and to the
      immortalization of tumor cells with inactivated WT1 alleles.

PMID- 7588598
TI  - Soluble constituents of the ER lumen are required for GPI anchoring of a model
      protein.
AB  - Transfer of a glycosylphosphatidylinositol (GPI) anchor to proteins carrying a C
      terminal GPI-directing signal sequence occurs after protein translocation across
      the endoplasmic reticulum (ER). We describe the translocation and GPI
      modification of a model protein, preprominiPLAP, in ER microsomes depleted of
      lumenal content by high pH washing. In untreated microsomes preprominiPLAP was
      processed to prominiPLAP and GPI-anchored miniPLAP. Both products were fully
      translocated, since they resisted proteinase K treatment of the microsomes, and
      both behaved as membrane proteins by the carbonate extraction criterion.
      Microsomes depleted of lumenal content were able to translocate and process
      preprominiPLAP to give protease-protected prominiPLAP, but were unable to convert
      prominiPLAP to miniPLAP. Loss of GPI anchoring capacity occurred with a wash of
      pH > 9.5. If the alkaline wash was performed after formation of prominiPLAP
      conversion to miniPLAP was relatively unimpaired. The results indicate that
      constituents of the ER lumen, possibly chaperones interacting with the proprotein
      and/or the GPI anchor precursor, are required in the initial steps of GPI
      anchoring.

PMID- 7588599
TI  - An investigation of the role of transmembrane domains in Golgi protein retention.
AB  - The single transmembrane domains (TMDs) of the resident glycosylation enzymes of
      the Golgi apparatus are involved in preventing these proteins moving beyond the
      Golgi. It has been proposed that either the TMDs associate, resulting in the
      formation of large oligomers of Golgi enzymes, or that they mediate the lateral
      segregation of the enzymes between lipid microdomains. Evidence for either type
      of interaction has been sought by examining the retention of sialyltransferase
      (ST), an enzyme of the mammalian trans Golgi. No evidence could be obtained for
      specific interactions or 'kin recognition' between ST and other proteins of the
      trans Golgi. Moreover, it is shown that the previously described kin recognition
      between enzymes of the medial Golgi involves the lumenal portions of these
      proteins rather than their TMDs. To investigate further the role of the ST TMD,
      the effects on Golgi retention of various alterations in the TMD were examined.
      The addition or removal of residues showed that the efficiency of retention of ST
      is related to TMD length. Moreover, when a type I plasma membrane protein was
      expressed with a synthetic TMD of 23 leucines it appeared on the cell surface,
      but when the TMD was shortened to 17 leucines accumulation in the Golgi was
      observed. These observations are more consistent with lipid-based sorting of ST
      TMD, but they also allow for reconciliation with the kin recognition model which
      appears to act on sequences outside of the TMD.

PMID- 7588601
TI  - Protein ligands of the human adenovirus type 2 outer capsid identified by
      biopanning of a phage-displayed peptide library on separate domains of wild-type
      and mutant penton capsomers.
AB  - A filamentous phage-displayed random hexapeptide library was screened on the
      adenovirus type 2 (Ad2) penton capsomer and its separate domains, penton base,
      full-length fiber, fiber shaft and fiber knob. Affinity supports were designed to
      immobilize the penton ligate with a preferred orientation, via immuno-adsorption
      to pre-coated antibody. Three classes of phagotopes were distinguished in the
      eluates from the penton and fiber domains. (i) The first class represented
      peptide sequences identified in certain Ad2 capsid proteins, protein IIIa,
      protein pVIII, penton base and penton fiber. Data from specific ligand elution of
      phages bound to fiber and penton base wild-types and mutants suggested that the
      region overlapping the RLSNLLG motif at residues 254-260 in the penton base and
      the FNPVYP motif at residues 11-16 in the fiber tail formed mutual interacting
      sites in the penton capsomer. (ii) The second class consisted of phagotopes
      homologous to peptide sequences found in host cell membrane proteins involved in
      receptor or adhesion functions. One of the most abundant species corresponded to
      a conserved motif present in the beta-strand B of type III modules of human
      fibronectin. In addition, phages which were screened for their failure to bind to
      penton base RGD mutants were found to carry consensus motifs to peptide sequences
      present in the RGD recognition site of human integrin beta subunits. (iii) The
      third class comprised peptide motifs common to both viral and cellular proteins,
      suggesting that a mechanism of ligand exchange could occur during virus entry and
      uncoating, and virus assembly and release.

PMID- 7588600
TI  - Clostridial neurotoxins compromise the stability of a low energy SNARE complex
      mediating NSF activation of synaptic vesicle fusion.
AB  - A 20S complex composed of the cytosolic fusion proteins NSF and SNAP and the
      synaptosomal SNAP receptors (SNAREs) synaptobrevin, syntaxin and SNAP-25 is
      essential for synaptic vesicle exocytosis. Formation of this complex is thought
      to be regulated by synaptotagmin, the putative calcium sensor of neurotransmitter
      release. Here we have examined how different inhibitors of neurotransmitter
      release, e.g. clostridial neurotoxins and a synaptotagmin peptide, affect the
      properties of the 20S complex. Cleavage of synaptobrevin and SNAP-25 by the
      neurotoxic clostridial proteases tetanus toxin and botulinum toxin A had no
      effect on assembly and disassembly of the 20S complex; however, the stability of
      its SDS-resistant SNARE core was compromised. This SDS-resistant low energy
      conformation of the SNAREs constitutes the physiological target of NSF, as
      indicated by its ATP-dependent disassembly in the presence of SNAP and NSF.
      Synaptotagmin peptides caused inhibition of in vitro binding of this protein to
      the SNAREs, a result that is inconsistent with synaptotagmin's proposed role as a
      regulator of SNAP binding. Our data can be reconciled by the idea that NSF and
      SNAP generate synaptotagmin-containing intermediates in synaptic vesicle fusion,
      which catalyse neurotransmitter release.

PMID- 7588603
TI  - The role of a positioned nucleosome at the Drosophila melanogaster hsp26
      promoter.
AB  - The regulatory region of Drosophila melanogaster hsp26 includes a positioned
      nucleosome located between the two DNase I hypersensitive (DH) sites that
      encompass the critical heat shock elements (HSEs). To test the role of this
      nucleosome in regulated expression, transgenic flies containing hsp26-lacZ fusion
      genes with alterations in the nucleosome-associated region have been generated.
      The positioned nucleosome is associated with a DNA sequence that does not itself
      contain any critical regulatory elements for heat shock-inducible expression. The
      nucleosome-associated sequence can be deleted, reversed, duplicated or replaced
      by a random sequence with no significant effect on DH site formation and gene
      expression. Analyses of hsp26 and hsp70 transgenes with spacing changes within
      the promoter region indicate that the location of the (CT)n.(GA)n elements
      dictates the location of DH site formation. Wrapping the DNA between the
      regulatory elements around a nucleosome is as effective for gene expression as
      placing the regulatory elements close to each other. A loss of inducible gene
      expression was observed when the nucleosome-associated DNA was replaced with
      sequences which appear to misdirect nucleosome placement. The results indicate
      considerable flexibility in the spacing between DH regulatory sites.

PMID- 7588602
TI  - Subunit composition of G(o) proteins functionally coupling galanin receptors to
      voltage-gated calcium channels.
AB  - The neuropeptide galanin is widely expressed in the central nervous system and
      other tissues and induces different cellular reactions, e.g. hormone release from
      pituitary and inhibition of insulin release from pancreatic B cells. By
      microinjection of antisense oligonucleotides we studied the question as to which
      G proteins mediate the galanin-induced inhibition of voltage-gated Ca2+ channels
      in the rat pancreatic B-cell line RINm5F and in the rat pituitary cell line GH3.
      Injection of antisense oligonucleotides directed against alpha 01, beta 2, beta
      3, gamma 2 and gamma 4 G protein subunits reduced the inhibition of Ca2+ channel
      current which was induced by galanin, whereas no change was seen after injection
      of cells with antisense oligonucleotides directed against alpha i, alpha q, alpha
      11, alpha 14, alpha 15, beta 1, beta 4, gamma 1, gamma 3, gamma 5, or gamma 7 G
      protein subunits or with sense control oligonucleotides. In view of these data
      and of previous results, we conclude that the galanin receptors in GH3 and in
      RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2
      gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently.
      The latter G protein composition was previously shown to be used by muscarinic M4
      receptors to inhibit Ca2+ channels.

PMID- 7588606
TI  - The T protein encoded by Brachyury is a tissue-specific transcription factor.
AB  - The mouse Brachyury (T) gene is required for differentiation of the notochord and
      formation of mesoderm during posterior development. Homozygous embryos lacking T
      activity do not develop a trunk and tail and die in utero. The T gene is
      specifically expressed in notochord and early mesoderm cells in the embryo.
      recent data have demonstrated that the T protein is localized in the cell nucleus
      and specifically binds to a palindrome of 20 bp (the T site) in vitro. We show
      that the T protein activates expression of a reporter gene in HeLa cells through
      binding to the T site. Thus T is a novel tissue-specific transcription factor. It
      consists of a large N-terminal DNA binding domain (amino acids 1-229) and two
      pairs of transactivation and repression domains in the C-terminal protein half. T
      can also transactivate transcription through variously oriented and spaced T
      sites, a fact that may be relevant in the search for genes controlled by T
      protein and important in mesoderm development.

PMID- 7588605
TI  - CBP-induced stimulation of c-Fos activity is abrogated by E1A.
AB  - The CBP protein stimulates transcription of cAMP-responsive genes by binding to
      the phosphorylated activation domain of the CREB transcription factor. Here we
      show that CBP stimulates transcription of Fos/Jun activity in F9 cells and that
      this response of mediated, at least partly, via c-Fos. We show that CBP binds c
      Fos in a phosphorylation-independent manner in vitro, using a domain distinct
      from that required to bind CREB. When this CBP domain is linked to the activation
      domain of VP16 it can stimulate GAL4-Fos activity in vivo. The domain of CBP that
      binds c-Fos is also used to contact the E1A protein. We therefore asked whether
      the documented repression of AP1 activity by E1A is due to sequestration of CBP
      from c-Fos. We show that E1A 12S can repress c-Fos activation functions. The use
      of E1A mutants indicates that binding of CBP, but not RB, to E1A is essential for
      E1A-mediated repression. These data support a model whereby E1A can modulate AP1
      activity by directly competing for the CBP co-activator protein.

PMID- 7588604
TI  - The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of
      Ras and nuclear activator of transcription factors.
AB  - The HBx protein of hepatitis B virus (HBV) is a transcriptional activator that is
      required for infection and may play an important role in HBV-associated
      hepatocarcinogenesis. Recently, we and others have shown that HBx stimulates the
      Ras-Raf-MAP kinase cascade, which leads to enhanced cell proliferation and the
      activation of transcription factors AP-1 and NF-kappa B. Other studies have shown
      that HBx can activate transcription by interacting directly with nuclear
      components of the transcription machinery. Therefore we examined the basis for
      the different reported activities of HBx. Here, we show that HBx is a complex
      protein, displaying independent activities in different intracellular locations.
      The intracellular distribution of HBx protein was first investigated using
      scanning confocal laser immunomicroscopy and by genetic studies. Our work has
      established that HBx expressed in cultured cells is found authentically in both
      the cytoplasm and the nucleus. HBx is not strongly associated with any
      intracellular structures, but some preferential accumulation was observed near
      the cell surface. Next, HBx variants were constructed containing a functional or
      mutant nuclear localization sequence. We show that when HBx is engineered to
      relocate exclusively to the nucleus, it no longer activates the Ras-Raf-MAP
      kinase cascade, nor does it activate transcription factors AP-1 and NF-kappa B.
      Surprisingly, nuclear HBx fully retains the ability to stimulate HBV enhancer I,
      which is activated independently of the Ras and protein kinase C pathways.
      Therefore HBx protein stimulates signal transduction pathways in the cytoplasm
      and transactivates transcription elements in the nucleus. Furthermore, SV40 T
      antigen is shown to induce the nuclear sequestration of HBx protein and to block
      its activation of NF-kappa B, demonstrating that HBx is regulated by proteins
      that alter its intracellular distribution. The conflicting functions of HBx
      protein in viral infection and possibly carcinoma may involve the regulation of
      its differential distribution in the cell.

PMID- 7588607
TI  - Heterodimeric Drosophila gap gene protein complexes acting as transcriptional
      repressors.
AB  - The Drosophila gap gene Kruppel (Kr) encodes a transcriptional regulator. It acts
      both as an integral part of the Drosophila segmentation gene in the early
      blastoderm and in a variety of tissues and organs at later stages of
      embryogenesis. In transfected tissue culture cells, the Kr protein (Kr) was shown
      to both activate and repress gene expression in a concentration-dependent manner
      when acting from a single binding site close to the promoter. Here we show that
      KR can associate with the transcription factors encoded by the gap genes knirps
      (kni) and hunchback (hb) which affect KR-dependent gene expression in Drosophila
      tissue culture cells. The association of DNA-bound hb protein or free kni protein
      with distinct but different regions of KR results in the formation of DNA-bound
      transcriptional repressor complexes. Our results suggest that individual
      transcription factors can associate to form protein complexes which act as direct
      repressors of transcription. The interactions shown here add an unexpected level
      of complexity to the control of gene expression.

PMID- 7588608
TI  - ERF: an ETS domain protein with strong transcriptional repressor activity, can
      suppress ets-associated tumorigenesis and is regulated by phosphorylation during
      cell cycle and mitogenic stimulation.
AB  - ERF (ETS2 Repressor Factor) is a novel member of the ets family of genes, which
      was isolated by virtue of its interaction with the ets binding site (EBS) within
      the ETS2 promoter. The 2.7 kb ubiquitously expressed ERF mRNA encodes a 548 amino
      acid phosphoprotein that exhibits strong transcriptional repressor activity on
      promoters that contain an EBS. The localization of the DNA-binding domain of the
      protein at the N-terminus and th repression domain at the C-terminus is
      reminiscent of the organization of ELK1-like members of the ets family; however,
      there is no significant homology between ERF and ELK1 or any other ets member
      outside the DNA-binding domain. The repressor activity of ERF can antagonize the
      activity of other ets genes that are known transcriptional activators.
      Furthermore, ERF can suppress the ets-dependent transforming activity of the gag
      myb-ets fusion oncogene of ME26 virus. Although ERF protein levels remain
      constant throughout the cell cycle, the phosphorylation level of the protein is
      altered as a function of the cell cycle and after mitogenic stimulation. The ERF
      protein is also hyperphosphorylated in cells transformed by the activated Ha-ras
      and v-src genes and the transcription repressor activity of ERF is decreased
      after co-transfection with activated Ha-ras or the kinase domain of the c-Raf-1
      gene, indicating that ERF activity is probably regulated by the ras/MAPK pathway.
      Consistent with the in vivo phosphorylation and inactivation by ras, ERF is
      efficiently phosphorylated in vitro by Erk2 and cdc2/cyclin B kinases, at sites
      similar to those detected in vivo. Furthermore, a single mutation at position 526
      results in the loss of a specific phosphopeptide both in in vivo and in vitro (by
      Erk2) labeling. Substitution of Thr526 for glutamic acid also decreases the
      repression ability of ERF. Our data suggest a model in which modulation of ERF
      activity is involved in the transcriptional regulation of genes activated during
      entry into G1 phase. Obstruction of the ERF repressor function by the
      transactivating members of the ets family of genes (i.e.gag-myb-ets) may be
      essential for the control of genes involved in cell proliferation and may also
      underlie their tumorigenic effects.

PMID- 7588609
TI  - Fission yeast Rep2 is a putative transcriptional activator subunit for the cell
      cycle 'start' function of Res2-Cdc10.
AB  - In the yeast cell cycle 'start' requires sets of the Cdc10/ SWI family of
      transcriptional factors which activate the MCB cis elements contained in genes
      essential for S phase progression. Fission yeast possess two such overlapping
      systems, Res1-Cdc10 and Res2-Cdc10, both of which act to start the mitotic and
      meiotic cycles. We have recently isolated rep2+ as a multicopy suppressor of a
      temperature-sensitive cdc10 mutant which encodes a zinc finger protein. Here we
      show that the Rep2 zinc finger protein is an essential component of the active
      Res2-Cdc10 transcriptional regulator complex and likely to play a role in the
      control of cell cycle 'start'. Our data suggest that Rep2 is a transcriptional
      activator subunit which interacts with the MCB binding subunit complex formed by
      Res2 and Cdc10.

PMID- 7588610
TI  - Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of
      Saccharomyces cerevisiae.
AB  - In budding yeast G1 cells increase in cell mass until they reach a critical cell
      size, at which point (called Start) they enter S phase, bud and duplicate their
      spindle pole bodies. Activation of the Cdc28 protein kinase by G1-specific
      cyclins Cln1, Cln2 or Cln3 is necessary for all three Start events.
      Transcriptional activation of CLN1 and CLN2 by SBF and MBF transcription factors
      also requires an active Cln-Cdc28 kinase and it has therefore been proposed that
      the sudden accumulation of CLN1 and CLN2 transcripts during late G1 occurs via a
      positive feedback loop. We report that whereas Cln1 and Cln2 are required for the
      punctual execution of most, if not all, other Start-related events, they are not
      required for the punctual activation of SBF- or MBF-driven transcription. Cln3,
      on the other hand, is essential. By turning off cyclin B proteolysis and turning
      on proteolysis of the cyclin B-Cdc28 inhibitor p40SIC1, Cln1 and Cln2 kinases
      activate cyclin B-Cdc28 kinases and thereby trigger S phase. Thus the
      accumulation of Cln1 and Cln2 kinases which starts the yeast cell cycle is set in
      motion by prior activation of SBF- and MBF-mediated transcription by Cln3-Cdc28
      kinase. This dissection of regulatory events during late G1 demands a rethinking
      of Start as a single process that causes cells to be committed to the mitotic
      cell cycle.

PMID- 7588612
TI  - Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction
      of cyclins A, B and B3.
AB  - While entry into mitosis is triggered by activation of cdc2 kinase, exit from
      mitosis requires inactivation of this kinase. Inactivation results from
      proteolytic degradation of the regulatory cyclin subunits during mitosis. At
      least three different cyclin types, cyclins A, B and B3, associate with cdc2
      kinase in higher eukaryotes and are sequentially degraded in mitosis. We show
      here that mutations in the Drosophila gene fizzy (fzy) block the mitotic
      degradation of these cyclins. Moreover, expression of mutant cyclins (delta
      cyclins) lacking the destruction box motif required for mitotic degradation
      affects mitotic progression at distinct stages. Deltacyclin A results in a delay
      in metaphase, deltacyclin B in an early anaphase arrest and deltacyclin B3 in a
      late anaphase arrest, suggesting that mitotic progression beyond metaphase is
      ordered by the sequential degradation of these different cyclins. Coexpression of
      deltacyclins A, B and B3 allows a delayed separation of sister chromosomes, but
      interferes wit chromosome segregation to the poles. Mutations in fzy block both
      sister chromosome separation and segregation, indicating that fzy plays a crucial
      role in the metaphase/anaphase transition.

PMID- 7588611
TI  - Identification of a Myc-dependent step during the formation of active G1 cyclin
      cdk complexes.
AB  - Activation of conditional alleles of Myc can induce proliferation in quiescent
      cells. We now report that induction of Myc in density-arrested fibroblasts
      triggers rapid hyperphosphorylation of the retinoblastoma protein and activation
      of both cyclin D1- and cyclin E-associated kinase activities in the absence of
      significant changes in the amounts of cyclin-cdk complexes. Kinase activation by
      Myc is blocked by inhibitors of transcription and requires intact DNA binding and
      heterodimerization domains of Myc. Activation of cyclin E-cdk2 kinase in serum
      starved cells occurs in two steps. The first is induced by Myc and involves the
      release of a 120 kDa cyclin E-cdk2 complex from a 250 kDa inactive complex that
      is present in starved cells. This is necessary, but not sufficient, to generate
      full kinase activity, as cdc25 phosphatase activity is limiting in the absence of
      external growth factors. In vivo cdc25 activity can be supplied by the addition
      of growth factors. In vitro recombinant cdc25a strongly activates the 120 kDa,
      but only poorly activates the 250 kDa cyclin E-cdk2 complex. Our data show that
      two distinct signals, one of which is supplied by Myc, are necessary for
      consecutive steps during growth factor-induced formation of active cyclin E-cdk2
      complexes in G(o)-arrested rodent fibroblasts.

PMID- 7588616
TI  - Interaction of tRNAs with the ribosome at the A and P sites.
AB  - In vitro transcribed tRNA(Phe) analogues from Escherichia coli containing up to
      four randomly distributed A, G, U or C phosphorothioated nucleotides were used to
      investigate contact patterns with the ribosome in the A and P sites. The tRNAs
      were biologically active. Molecular iodine (I2) can trigger a break in the sugar
      phosphate backbone at phosphorothioated positions of the ribosomal bound tRNAs if
      contacts with ribosomal components do not prevent access of the iodine. Highly
      differentiated protection patterns were found which were strikingly different in
      the A and P sites, respectively. Strong protections accumulated in the T psi C
      loop and no protection was seen in the extra-arm region in both sites, whereas
      the phosphates in the anticodon loop are more strongly protected in the A site.
      Strong common protections in both the A and P sites were found neighbouring
      universally or semi-universally conserved bases in prominent regions of the
      tertiary structure of tRNAs: Y11, Y32, U33, psi55, C56, A58 and Y60. These bases
      are therefore candidates for 'identity elements' in ribosomal tRNA recognition.
      The data further indicate that tRNAs change their conformations upon binding to
      either ribosomal site.

PMID- 7588614
TI  - Relative orientation of RNA helices in a group 1 ribozyme determined by helix
      extension electron microscopy.
AB  - The relative orientation of helical elements in a folded RNA molecule provides
      key information about its three-dimensional architecture. We have developed a
      method that involves extending peripheral helices of an RNA, mounting for
      electron microscopy in the absence of protein and measuring interhelical angles.
      As a control, extended anticodon and acceptor stems of tRNA(Phe) were found to
      form a 92 +/- 20 degrees angle, consistent with the X-ray structure. Single,
      double and triple extensions (50-80 bp) of helical elements P2.1, P6b and P8 of
      the Tetrahymena group I ribozyme did not alter its catalytic activity. The
      measured angle between P6b and P8 is consistent with the Michel-Westhof
      structural model, while the P2.1-P6b and P2.1-P8 angles allow P2.1 to be
      positioned in the model. The angle distributions of the ribozyme are broader than
      those of the tRNA, which may reflect the dynamics of the RNA. Helix extension
      allows low-resolution electron microscopy to provide much higher resolution
      information about the disposition of helical elements in RNA. It should be
      applicable to diverse RNAs and ribonucleoprotein complexes.

PMID- 7588615
TI  - A common maturation pathway for small nucleolar RNAs.
AB  - We have shown that precursors of U3, U8 and U14 small nucleolar RNAs (snoRNAs)
      are not exported to the cytoplasm after injection into Xenopus oocyte nuclei but
      are selectively retained and matured in the nucleus, where they function in pre
      rRNA processing. Our results demonstrate that Box D, a conserved sequence element
      found in these and most other snoRNAs, plays a key role in their nuclear
      retention, 5' cap hypermethylation and stability. Retention of U3 and U8 RNAs in
      the nucleus is saturable and relies on one or more common factors.
      Hypermethylation of the 5' caps of U3 RNA occurs efficiently in oocyte nuclear
      extracts lacking nucleoli, suggesting that precursor snoRNAs are matured in the
      nucleoplasm before they are localized to the nucleolus. Surprisingly, m7G-capped
      precursors of spliceosomal small nuclear RNAs (snRNAs) such as pre-U1 and U2, can
      be hypermethylated in nuclei if the RNAs are complexed with Sm proteins. This
      raises the possibility that a single nuclear hypermethylase activity may act on
      both nucleolar and spliceosomal snRNPs.

PMID- 7588613
TI  - Bcr and Raf form a complex in vivo via 14-3-3 proteins.
AB  - In a yeast two-hybrid screen we identified a member of the 14-3-3 family of
      proteins that can bind to Bcr. 14-3-3 beta binds to the serine/threonine rich
      region B in the kinase domain encoded by the first exon. In this paper we show by
      co-immunoprecipitation that Bcr binds to Raf in vivo and we argue that this
      interaction is mediated by 14-3-3 dimers, based on the following findings. First,
      14-3-3 isoforms bind to both Raf and Bcr. Second, Bcr does not bind to Raf
      directly in the two-hybrid system, but co-expression of 14-3-3 beta allows
      complex formation. Third, Bcr, 14-3-3 proteins and Raf co-elute in gel filtration
      and in sequential ion exchange chromatography and the three proteins can be co
      immunoprecipitated from the the separate fractions, indicating that they are
      present in a ternary complex. Moreover, approximately 10 times more Raf is bound
      to Bcr, and vice versa, in the membrane fraction (where Raf is activated) than in
      the cytosolic fraction. We suggest a new function for 14-3-3 proteins as a novel
      type of new function for 14-3-3 proteins as a novel type of adaptor which acts by
      dimerization and binding to different proteins.

PMID- 7588617
TI  - Two distinct recognition signals define the site of endonucleolytic cleavage at
      the 5'-end of yeast 18S rRNA.
AB  - Three of the four eukaryotic ribosomal RNA molecules (18S, 5.8S and 25-28S rRNA)
      are transcribed as a single precursor, which is subsequently processed into the
      mature species by a complex series of cleavage and modification reactions. Early
      cleavage at site A1 generates the mature 5'-end of 18S rRNA. Mutational analyses
      have identified a number of upstream regions in the 5' external transcribed
      spacer (5' ETS), including a U3 binding site, which are required in cis for
      processing at A1. Nothing is known, however, about the requirement for cis-acting
      elements which define the position of the 5'-end of the 18S rRNA or of any other
      eukaryotic rRNA. We have introduced mutations around A1 and analyzed them in vivo
      in a genetic background where the mutant pre-rRNA is the only species
      synthesized. The results indicate that the mature 5'-end of 18S rRNA in yeast is
      identified by two partially independent recognition systems, both defining the
      same cleavage site. One mechanism identifies the site of cleavage at A1 in a
      sequence-specific manner involving recognition of phylogenetically conserved
      nucleotides immediately upstream of A1 in the 5' ETS. The second mechanism
      specifies the 5'-end of 18S rRNA by spacing the A1 cleavage at a fixed distance
      of 3 nt from the 5' stem-loop/pseudoknot structure located within the mature
      sequence. The 5' product of the A1 processing reaction can also be identified,
      showing that, in contrast to yeast 5.8S rRNA, the 5'-end of 18S rRNA is generated
      by endonucleolytic cleavage.

PMID- 7588618
TI  - The phage Mu transpososome core: DNA requirements for assembly and function.
AB  - The two chemical steps of phage Mu transpositional recombination, donor DNA
      cleavage and strand transfer, take place within higher order protein-DNA
      complexes called transpososomes. At the core of these complexes is a tetramer of
      MuA (the transposase), bound to the two ends of the Mu genome. While
      transpososome assembly normally requires a number of cofactors, under certain
      conditions only MuA and a short DNA fragment are required. DNA requirements for
      this process, as well as the stability and activity of the ensuing complexes,
      were established. The divalent cation normally required for assembly of the
      stable complex could be omitted if the substrate was prenicked, if the flanking
      DNA was very short or if the two flanking strands were non-complementary. The
      presence of a single nucleotide beyond the Mu genome end on the non-cut strand
      was critical for transpososome stability. Donor cleavage additionally required at
      least two flanking nucleotides on the strand to be cleaved. The flanking DNA
      double helix was destabilized, implying distortion of the DNA near the active
      site. Although donor cleavage required Mg2+, strand transfer took place in the
      presence of Ca2+ as well, suggesting a conformational difference in the active
      site for the two chemical steps.

PMID- 7588621
TI  - Molecular mechanism of the calcium-induced conformational change in the spectrin
      EF-hands.
AB  - Calcium is a universally employed cytosolic messenger in eukaryotic cells. Most
      of the proteins that bind signalling calcium are members of the calmodulin
      superfamily and share two or more helix-loop-helix motifs known as EF-hands. A
      model, based on structure comparison of different domains and supported by
      preliminary NMR data, has suggested that EF-hands involved in signal transduction
      undergo a major conformational change upon calcium binding from a 'closed' to an
      'open' state allowing protein-protein interaction. We have determined the
      solution structures of the EF-hand pair from alpha-spectrin in the absence and in
      the presence of calcium. The structures are in the closed and open conformation
      respectively, providing a definite experimental proof for the closed-to-open
      model. Our results allow formulation of the rules which govern the movement
      induced by calcium. These rules may be generalized to other EF-hands since the
      key residues involved are conserved within the calmodulin family.

PMID- 7588620
TI  - The 3-D structure of a zinc metallo-beta-lactamase from Bacillus cereus reveals a
      new type of protein fold.
AB  - The 3-D structure of Bacillus cereus (569/H/9) beta-lactamase (EC 3.5.2.6), which
      catalyses the hydrolysis of nearly all beta-lactams, has been solved at 2.5 A
      resolution by the multiple isomorphous replacement method, with density
      modification and phase combination, from crystals of the native protein and of a
      specially designed mutant (T97C). The current model includes 212 of the 227 amino
      acid residues, the zinc ion and 10 water molecules. The protein is folded into a
      beta beta sandwich with helices on each external face. To our knowledge, this
      fold has never been observed. An approximate internal molecular symmetry is
      found, with a 2-fold axis passing roughly through the zinc ion and suggesting a
      possible gene duplication. The active site is located at one edge of the beta
      beta sandwich and near the N-terminal end of a helix. The zinc ion is coordinated
      by three histidine residues (86, 88 and 149) and a water molecule. A sequence
      comparison of the relevant metallo-beta-lactamases, based on this protein
      structure, highlights a few well-conserved amino acid residues. The structure
      shows that most of these residues are in the active site. Among these, aspartic
      acid 90 and histidine 210 participate in a proposed catalytic mechanism for beta
      lactam hydrolysis.

PMID- 7588619
TI  - Journey to the surface of the cell: Fos regulation and the SRE.

PMID- 7588622
TI  - Production of intracellular amyloid-containing fragments in hippocampal neurons
      expressing human amyloid precursor protein and protection against amyloidogenesis
      by subtle amino acid substitutions in the rodent sequence.
AB  - A distinguishing feature of Alzheimer's disease (AD) is the deposition of amyloid
      plaques in brain parenchyma. These plaques arise by the abnormal accumulation of
      beta A4, a proteolytic fragment of amyloid precursor protein (APP). Despite the
      fact that neurons are dramatically affected in the course of the disease, little
      is known about the neuronal processing of APP. To address this question we have
      expressed in fully mature, synaptically active rat hippocampal neurons, the
      neuronal form of human APP (APP695), two mutant forms of human APP associated
      with AD, and the mouse form of APP (a species known not to develop amyloid
      plaques). Protein expression was achieved via the Semliki Forest Virus system.
      Expression of wild type human APP695 resulted in the secretion of beta A4-amyloid
      peptide and the intracellular accumulation of potential amyloidogenic and non
      amyloidogenic fragments. The relative amount of amyloid-containing fragments
      increased dramatically during expression of the clinical mutants, while it
      decreased strongly when the mouse form of APP was expressed. 'Humanizing' the
      rodent APP sequence by introducing three mutations in the beta A4-region also led
      to increased production of amyloid peptide to levels similar to those obtained
      with human APP. The single Gly601 to Arg substitution alone was sufficient to
      triple the ratio of beta A4-peptide to non-amyloidogenic p3-peptide. Due to the
      capacity of these cells to secrete and accumulate intracellular amyloid
      fragments, we hypothesize that in the pathogenesis of AD there is a positive feed
      back loop where neurons are both producers and victims of amyloid, leading to
      neuronal degeneration and dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588623
TI  - A ribosome-associated peptidyl-prolyl cis/trans isomerase identified as the
      trigger factor.
AB  - Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyse protein
      folding both in vitro and in vivo. We isolated a peptidyl-prolyl cis/trans
      isomerase (PPIase) which is specifically associated with the 50S subunit of the
      Escherichia coli ribosome. This association was abolished by adding at least 1.5
      M LiCl. Sequencing the N-terminal amino acids in addition to three proteolytic
      fragments totalling 62 amino acids revealed that this PPIase is identical to the
      E.coli trigger factor. A comparison of the amino acid sequence of trigger factor
      with those of other PPIase families shows little similarities, suggesting that
      trigger factor may represent an additional family of PPIases. Trigger factor was
      purified to homogeneity on a preparative scale from E.coli and its enzymatic
      properties were studied. In its activity towards oligopeptide substrates, the
      trigger factor resembles the FK506-binding proteins (FKBPs). Additionally, the
      pattern of subsite specificities with respect to the amino acid preceding proline
      in Suc-Ala-Xaa-Pro-Phe-4-nitroanilides is reminiscent of FKBPs. However, the
      PPIase activity of the trigger factor was not inhibited by either FK506 or by
      cyclosporin A at concentrations up to 100 microM. In vitro, the trigger factor
      catalysed the proline-limited refolding of a variant of RNase T1 much better than
      all other PPIases that have been examined so far.

PMID- 7588624
TI  - STT3, a highly conserved protein required for yeast oligosaccharyl transferase
      activity in vivo.
AB  - N-linked glycosylation is a ubiquitous protein modification, and is essential for
      viability in eukaryotic cells. A lipid-linked core-oligosaccharide is assembled
      at the membrane of the endoplasmic reticulum and transferred to selected
      asparagine residues of nascent polypeptide chains by the oligosaccharyl
      transferase (OTase) complex. Based on the synthetic lethal phenotype of double
      mutations affecting the assembly of the lipid-linked core-oligosaccharide and the
      OTase activity, we have performed a novel screen for mutants in Saccharomyces
      cerevisiae with altered N-linked glycosylation. Besides novel mutants deficient
      in the assembly of the lipid-linked oligosaccharide (alg mutants), we identified
      the STT3 locus as being required for OTase activity in vivo. The essential STT3
      protein is approximately 60% identical in amino acid sequence to its human
      homologue. A mutation in the STT3 locus affects substrate specificity of the
      OTase complex in vivo and in vitro. In stt3-3 cells very little glycosyl transfer
      occurs from incomplete lipid-linked oligosaccharide, whereas the transfer of full
      length Glc3Man9GlcNAc2 is hardly affected as compared with wild-type cells.
      Depletion of the STT3 protein results in loss of transferase activity in vivo and
      a deficiency in the assembly of OTase complex.

PMID- 7588625
TI  - An acidic sequence within the cytoplasmic domain of furin functions as a
      determinant of trans-Golgi network localization and internalization from the cell
      surface.
AB  - The mammalian endopeptidase, furin, is predominantly localized to the trans-Golgi
      network (TGN) at steady state. The localization of furin to this compartment
      seems to be the result of a dynamic process in which the protein undergoes
      cycling between the TGN and the plasma membrane. Both TGN localization and
      internalization from the plasma membrane are mediated by targeting information
      contained within the cytoplasmic domain of furin. Here, we report the results of
      a mutagenesis analysis aimed at identifying the source(s) of targeting
      information within the furin cytoplasmic domain. Our studies show that there are
      at least two cytoplasmic determinants that contribute to the steady-state
      localization and trafficking of furin. The first determinant corresponds to a
      canonical tyrosine-based motif, YKGL (residues 758-761), that functions mainly as
      an internalization signal. The second determinant consists of a strongly
      hydrophilic sequence (residues 766-783) that contains a large cluster of acidic
      residues (E and D) and is devoid of any tyrosine-based or di-leucine-based
      motifs. This second determinant is capable of conferring localization to the TGN
      as well as mediating internalization from the plasma membrane. Thus, these
      observations establish the existence of a novel, autonomous determinant distinct
      from sorting signals described previously.

PMID- 7588626
TI  - Isolation of a psaF-deficient mutant of Chlamydomonas reinhardtii: efficient
      interaction of plastocyanin with the photosystem I reaction center is mediated by
      the PsaF subunit.
AB  - The PsaF polypeptide of photosystem I (PSI) is located on the lumen side of the
      thylakoid membrane and its precise role is not yet fully understood. Here we
      describe the isolation of a psaF-deficient mutant of the green alga Chlamydomonas
      reinhardtii generated by co-transforming the nuclear genome of the cw15-arg7A
      strain with two plasmids: one harboring a mutated version of the psaF gene and
      the other containing the argininosuccinate lyase gene conferring arginine
      prototrophy. This psaF mutant still assembles a functional PSI complex and is
      capable of photoautotrophic growth. However, electron transfer from plastocyanin
      to P700+, the oxidized reaction center chlorophyll dimer, is dramatically reduced
      in the mutant, indicating that the PsaF subunit plays an important role in
      docking plastocyanin to the PSI complex. These results contrast with those
      obtained previously with a cyanobacterial psaF-, psaJ- double mutant where no
      phenotype was apparent.

PMID- 7588627
TI  - Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells
      in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for
      Down syndrome.
AB  - The copper-zinc superoxide dismutase (CuZnSOD) gene resides on chromosome 21 and
      is overexpressed in Down syndrome (DS) patients. Transgenic CuZnSOD mice with
      elevated levels of CuZnSOD were used to determine whether, as in DS,
      overexpression of CuZnSOD was also associated with thymus and bone marrow
      abnormalities. Three independently derived transgenic CuZnSOD strains had
      abnormal thymi showing diminution of the cortex and loss of corticomedullary
      demarcation, resembling thymic defects in children with DS. Transgenic CuZnSOD
      mice were also more sensitive than control mice to in vivo injection of
      lipopolysaccharide (LPS), reflected by an earlier onset and enhanced apoptotic
      cell death in the thymus. This higher susceptibility to LPS-induced apoptosis was
      associated with an increased production of hydrogen peroxide and a higher degree
      of lipid peroxidation. When cultured under suboptimal concentrations of
      interleukin 3 or in the presence of tumour necrosis factor, bone marrow cells
      from transgenic CuZnSOD mice produced 2- to 3-fold less granulocyte and
      macrophage colonies than control. The results indicate that transgenic CuZnSOD
      mice have certain thymus and bone marrow abnormalities which are similar to those
      found in DS patients, and that the defects are presumably due to an increased
      oxidative damage resulting in enhanced cell death by apoptosis.

PMID- 7588628
TI  - DNA damage in human B cells can induce apoptosis, proceeding from G1/S when p53
      is transactivation competent and G2/M when it is transactivation defective.
AB  - Cisplatin treatment of Epstein-Barr virus-immortalized human B lymphoblastoid
      cell lines (LCLs) results in p53-mediated apoptosis which occurs largely in a
      population of cells at the G1/S boundary of the cell cycle. Cell cycle
      progression appears to be required for this apoptosis because arresting cells
      earlier in G1 inhibited apoptosis despite the accumulation of p53. Overexpression
      of wild-type p53 also induces apoptosis in an LCL. Therefore six mutant genes
      derived from Burkitt's lymphoma (BL) cells were assayed for their ability to
      induce apoptosis when similarly overexpressed. The same genes were analysed in
      transient transfection assays for their ability to transactivate appropriate
      reporter plasmids. A correlation between the ability of p53 to transactivate and
      induce apoptosis was revealed. The only mutant capable of transactivation also
      induced apoptosis. Further analysis of the BL lines in which p53 had been
      characterized showed that whereas some lines were essentially resistant to
      cisplatin, three were rapidly induced to undergo apoptosis. All three have a
      single p53 allele encoding a mutant which is incapable of transactivation or (for
      two tested) mediating apoptosis when expressed in an LCL. Cell cycle analysis
      revealed that this apparently p53-independent apoptosis did not follow G1 arrest
      but in fact occurred largely in cells distributed in the G2/M phase of the cell
      cycle. These data suggest the existence of a second checkpoint in the G2 or M
      phase which, in the absence of a functional p53, is the primary point of entry
      into the apoptosis programme following DNA damage.

PMID- 7588629
TI  - A single amino acid in the SH3 domain of Hck determines its high affinity and
      specificity in binding to HIV-1 Nef protein.
AB  - We have examined the differential binding of Hck and Fyn to HIV-1 Nef to
      elucidate the structural basis of SH3 binding affinity and specificity. Full
      length Nef bound to Hck SH3 with the highest affinity reported for an SH3
      mediated interaction (KD 250 nM). In contrast to Hck, affinity of the highly
      homologous Fyn SH3 for Nef was too weak (KD > 20 microM) to be accurately
      determined. We show that this distinct specificity lies in a variable loop, the
      'RT loop', positioned close to conserved SH3 residues implicated in the binding
      of proline-rich (PxxP) motifs. A mutant Fyn SH3 with a single amino acid
      substitution (R96I) in its RT loop had an affinity (KD 380 nM) for Nef comparable
      with that of Hck SH3. Based on additional mutagenesis studies we propose that the
      selective recognition of Nef by Hck SH3 is determined by hydrophobic interactions
      involving an isoleucine residue in its RT loop. Although Nef contains a PxxP
      motif which is necessary for the interaction with Hck SH3, high affinity binding
      was only observed for intact Nef protein. The binding of a peptide containing the
      Nef PxxP motif showed > 300-fold weaker affinity for Hck SH3 than full-length
      Nef.

PMID- 7588630
TI  - Two different thresholds of wingless signalling with distinct developmental
      consequences in the Drosophila midgut.
AB  - Drosophila wingless encodes a Wnt protein which mediates communication between
      cells. Although wingless protein is secreted from cells, there is debate as to
      what is the range of wingless action. We examined the function of wingless in the
      larval midgut, and found that wingless acts at two different thresholds to
      pattern this tissue. Low wingless levels are required to promote the development
      of copper cells, highly differentiated midgut cells of the larval midgut that are
      specified by the homeotic gene labial. High wingless levels repress copper cell
      development and allow differentiation of an alternative cell type, called large
      flat cells. These two developmental outcomes reflect labial expression, which is
      stimulated at low levels and repressed at high levels of wingless signalling.
      Thus, midgut cells respond differentially to distinct wingless thresholds in
      terms of both gene control and cellular differentiation.

PMID- 7588632
TI  - Differential activation of c-fos promoter elements by serum, lysophosphatidic
      acid, G proteins and polypeptide growth factors.
AB  - The upstream regulatory region of the c-fos promoter contains two growth factor
      regulated promoter elements: the serum response element, which binds a ternary
      complex comprising serum response factor (SRF) and a ternary complex factor
      (TCF); and the sis-inducible element (SIE) which binds STAT transcription
      factors. We used transient transfection of c-fos promoter mutants in NIH 3T3
      cells to assess the contributions of these elements to activation by different
      extracellular stimuli. Colony-stimulating factor-1, platelet-derived growth
      factor and epidermal growth factor activate the c-fos promoter via cooperation of
      the SIE and the SRE; however, mutants that can bind SRF but not STATs or TCF
      remain inducible by whole serum. Activation by the SIE is context-dependent:
      interferons activate STAT DNA binding activity and transcription of SIE reporter
      genes, but not the c-fos promoter, which requires an additional ras-dependent
      signal. SRE activation by receptor tyrosine kinases requires TCF binding, and can
      be mediated by the TCF Elk-1. In contrast, SRE activation following activation of
      heterotrimeric G proteins by lysophosphatidic acid or aluminium fluoride ion
      requires SRF but is independent of TCF binding. These results suggest that
      heterotrimeric G proteins activate a signalling pathway distinct from those that
      activate the STATs and the TCFs, that controls SRF activity.

PMID- 7588631
TI  - MAT1 ('menage a trois') a new RING finger protein subunit stabilizing cyclin H
      cdk7 complexes in starfish and Xenopus CAK.
AB  - The kinase responsible for Thr161-Thr160 phosphorylation and activation of
      cdc2/cdk2 (CAK:cdk-activating kinase) has been shown previously to comprise at
      least two subunits, cdk7 and cyclin H. An additional protein co-purified with CAK
      in starfish oocytes, but its sequencing did not reveal any similarity with any
      known protein. In the present work, a cDNA encoding this protein is cloned and
      sequenced in both starfish and Xenopus oocytes. It is shown to encode a new
      member of the RING finger family of proteins with a characteristic C3HC4 motif
      located in the N-terminal domain. We demonstrate that the RING finger protein
      (MAT1: 'menage a trois') is a new subunit of CAK in both vertebrate and
      invertebrates. However, CAK may also exist in oocytes as heterodimeric complexes
      between cyclin H and cdk7 only. Stable heterotrimeric CAK complexes were
      generated in reticulocyte lysates programmed with mRNAs encoding Xenopus cdk7,
      cyclin H and MAT1. In contrast, no heterodimeric cyclin H-cdk7 complex could be
      immunoprecipitated from reticulocyte lysates programmed with cdk7 and cyclin H
      mRNAs only. Stabilization of CAK complexes by MAT1 does not involve
      phosphorylation of Thr176, as the Thr176-->Ala mutant of Xenopus cdk7 could
      engage as efficiently as wild-type cdk7 in ternary complexes. Even though
      starfish MAT1 is almost identical to Xenopus MAT1 in the RING finger domain, the
      starfish subunit could not replace the Xenopus subunit and stabilize cyclin H
      cdk7 in reticulocyte lysate, suggesting that the MAT1 subunit does not (or not
      only) interact with cyclin H-cdk7 through the RING finger domain.

PMID- 7588633
TI  - The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its
      transforming activity in NIH 3T3 cells.
AB  - The c-mos proto-oncogene product, Mos, is a serine/threonine kinase that can
      activate ERK1 and 2 mitogen-activated protein (MAP) kinases by direct
      phosphorylation of MAPK/ERK kinase (MEK). ERK activation is essential for
      oncogenic transformation of NIH 3T3 cells by Mos. In this study, we examined how
      mitogenic and oncogenic signalling from the Mos/MEK/ERK pathway reaches the
      nucleus to activate downstream target genes. We show that c-Fos (the c-fos
      protooncogene product), which is an intrinsically unstable nuclear protein, is
      metabolically highly stabilized, and greatly enhances the transforming efficiency
      of NIH 3T3 cells, by Mos. This stabilization of c-Fos required Mos-induced
      phosphorylation of its C-terminal region on Ser362 and Ser374, and double
      replacements of these serines with acidic (Asp) residues markedly increased the
      stability and transforming efficiency of c-Fos even in the absence of Mos.
      Moreover, activation of the ERK pathway was necessary and sufficient for the c
      Fos phosphorylation and stabilization by Mos. These results indicate that c-Fos
      undergoes stabilization, and mediates at least partly the oncogenic signalling,
      by the Mos/MEK/ERK pathway. The present findings also suggest that, in general,
      the ERK pathway may regulate the cell fate and function by affecting the
      metabolic stability of c-Fos.

PMID- 7588636
TI  - Both ambient temperature and the DnaK chaperone machine modulate the heat shock
      response in Escherichia coli by regulating the switch between sigma 70 and sigma
      32 factors assembled with RNA polymerase.
AB  - In Escherichia coli individual sigma factors direct RNA polymerase (RNAP) to
      specific promoters. Upon heat shock induction there is a transient increase in
      the rate of transcription of approximately 20 heat shock genes, whose promoters
      are recognized by the RNAP-sigma 32 rather than the RNAP-sigma 70 holoenzyme. At
      least three heat shock proteins, DnaK, DnaJ and GrpE, are involved in negative
      modulation of the sigma 32-dependent heat shock response. Here we show, using
      purified enzymes, that upon heat treatment of RNAP holoenzyme the sigma 70 factor
      is preferentially inactivated, whereas the resulting heat-treated RNAP core is
      still able to initiate transcription once supplemented with sigma 32 (or fresh
      sigma 70). Heat-aggregated sigma 70 becomes a target for the joint action of
      DnaK, DnaJ and GrpE proteins, which reactivate it in an ATP-dependent reaction.
      The RNAP-sigma 32 holoenzyme is relatively stable at temperatures at which the
      RNAP-sigma 70 holoenzyme is inactivated. Furthermore, we show that formation of
      the RNAP-sigma 32 holoenzyme is favored over that of RNAP-sigma 70 at elevated
      temperatures. We propose a model of negative autoregulation of the heat shock
      response in which cooperative action of DnaK, DnaJ and GrpE heat shock proteins
      switches transcription back to constitutively expressed genes through the
      simultaneous reactivation of heat-aggregated sigma 70, as well as sequestration
      of sigma 32 away from RNAP.

PMID- 7588635
TI  - Programming of a repressed but committed chromatin structure during early
      development.
AB  - The determination of chromatin for transcription during early development as well
      as the requirement for trans-acting factors during this period has been analysed
      in Xenopus. Basal transcription is repressed both during oogenesis and after the
      mid-blastula transition (MBT), and transactivators are required to relieve this
      repression. In contrast, transactivators cannot overcome the generalized
      transcriptional repression which occurs in embryos before MBT. However, they do
      bind to promoters leading to a repressed but preset chromatin structure.
      Experiments involving the pre-binding of TATA binding protein (TBP) or of the
      strong transactivator GAL4-VP16 further show that there is no limiting factor
      before the MBT, and that it is the recruitment and stabilization of the basal
      transcription machinery and not of transactivators which is repressed during
      early development. This multi-step process in gene activation, with activation of
      promoters temporally uncoupled from their commitment, may be of importance in the
      regulation of early embryonic events by providing molecular signposts for future
      determinations.

PMID- 7588634
TI  - In vivo regulation of interleukin-2 receptor alpha gene transcription by the
      coordinated binding of constitutive and inducible factors in human primary T
      cells.
AB  - IL-2R alpha transcription is developmentally restricted to T cells and
      physiologically dependent on specific stimuli such as antigen recognition. To
      analyse the mechanisms used to activate IL-2R alpha transcription as well as
      those used to block it in non-expressing cells, we determined the protein-DNA
      interactions at the IL-2R alpha locus in three different cell types using the
      DMS/LMPCR genomic footprinting method. CD25/IL-2R alpha can be efficiently
      induced in primary human T cells since approximately 100% express this gene when
      receiving an appropriate combination of mitogenic stimuli. To understand why IL
      2R alpha is not expressed in other haematopoietic cell types, we analysed BJAB B
      lymphoma cells which do not express the IL-2R alpha gene and contain
      constitutively active nuclear NF-kappa B. Primary fibroblasts from embryo and
      adult skin were selected to examine the mechanisms that may be used to keep the
      IL-2R alpha gene inactive in non-haematopoietic cells. The three main results
      are: (i) the stable in vivo occupancy of IL-2R alpha kappa B element in resting T
      cells, most probably by constitutive NF-kappa B p50 homodimer that could impair
      SRF binding to the flanking SRE/CArG box; (ii) its inducible occupancy by NF
      kappa B p50-p65 associated with the binding of an SRE/CArG box DNA-binding factor
      upon mitogenic stimulation; and (iii) a correlation between the precommitment of
      T cells to activation and the presence of stable preassembled protein-DNA
      complexes in contrast with the bare IL-2R alpha locus in non-T cells.

PMID- 7588637
TI  - Maturase and endonuclease functions depend on separate conserved domains of the
      bifunctional protein encoded by the group I intron aI4 alpha of yeast
      mitochondrial DNA.
AB  - Intron 4 alpha (aI4 alpha) of the yeast mitochondrial COXI gene is a mobile group
      I intron that contains a reading frame encoding both the homing endonuclease I
      SceII and a latent maturase capable of splicing both aI4 alpha and the fourth
      intron of the cytochrome b (COB) gene (bI4). The aI4 alpha reading frame is a
      member of a large gene family recognized by the presence of related dodecapeptide
      sequence motifs called P1 and P2. In this study, missense mutations of P1 and P2
      were placed in mitochondrial DNA by biolistic transformation. The effects of the
      mutations on intron mobility, endonuclease I-SceII activity and maturase function
      were tested. The mutations of P1 strongly affected mobility and endonuclease I
      SceII activity, but had little or no effect on maturase function; mutations of P2
      affected splicing but not mobility or endonuclease I-SceII activity.
      Surprisingly, the conditional (temperature-sensitive) mutations at P1 and P2
      block one or the other function of the protein but not both. This study indicates
      that the two functions depend on separate domains of the intron-encoded protein.

PMID- 7588638
TI  - Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit
      generated by alternative processing of a new member of a cytokine receptor gene
      cluster.
AB  - The cellular receptor for the alpha/beta interferons contains at least two
      components that interact with interferon. The ifnar1 component is well
      characterized and a putative ifnar2 cDNA has recently been identified. We have
      cloned the gene for ifnar2 and show that it produces four different transcripts
      encoding three different polypeptides that are generated by exon skipping,
      alternative splicing and differential use of polyadenylation sites. One
      polypeptide is likely to be secreted and two are transmembrane proteins with
      identical extracellular and transmembrane domains but divergent cytoplasmic tails
      of 67 and 251 amino acids. A mutant cell line U5A, completely defective in IFN
      alpha beta binding and response, has been isolated and characterized. Expression
      in U5A cells of the polypeptide with the long cytoplasmic domain reconstitutes a
      functional receptor that restores normal interferon binding, activation of the
      JAK/STAT signal transduction pathway, interferon-inducible gene expression and
      antiviral response. The IFNAR2 gene maps at 0.5 kb from the CRFB4 gene,
      establishing that together IFNAR2, CRFB4, IFNAR1 and AF1 form a cluster of class
      II cytokine receptor genes on human chromosome 21.

PMID- 7588643
TI  - Genetic heterogeneity in mammalian specific-locus mutation systems.

PMID- 7588641
TI  - Catalytic residues of gamma delta resolvase act in cis.
AB  - The resolvase protein of the gamma delta transposon is a site-specific
      recombinase that acts by a concerted break-and-join mechanism. To analyse the
      role of individual resolvase subunits in DNA strand cleavage, we have directed
      the binding of catalytic mutants to specific recombination crossover sites or
      half-sites. Our results demonstrate that the resolvase subunit bound at the half
      site proximal to each scissile phosphodiester bond provides the Ser10 nucleophile
      and Arg8, Arg68 and Arg71 residues essential for cleavage and covalent attachment
      to the DNA. Several other residues near the presumptive active site are also
      shown to act in cis. Double-strand cleavage at one crossover site can proceed
      independently of cleavage at the other site, although interactions between the
      resolvase dimers bound at the two crossover sites remain essential. An
      appropriately oriented heterodimer of active and inactive protomers can in most
      cases mediate either a 'top' or 'bottom' single-strand cleavage, suggesting that
      there is no obligatory order of strand cleavages. Top-strand cleavage is
      associated with the topoisomerase I activity of resolvase, suggesting that a
      functional asymmetry may be imposed on the crossover site by the structure of the
      active synapse.

PMID- 7588640
TI  - Sequence non-specific double-strand breaks and interhomolog interactions prior to
      double-strand break formation at a meiotic recombination hot spot in yeast.
AB  - The HIS4LEU2 meiotic recombination hot spot specifies two double-strand break
      (DSB) sites, I and II. Results presented demonstrate that DSBs at site I occur at
      many positions throughout a region of approximately 150 bp; we infer that breaks
      occur in a sequence non-specific fashion. Single-strand nicks at sites I and II
      are not detectable. Analysis of the effects of a 36 bp linker insertion at site I
      reveals the existence of communication along and between homologs prior to DSB
      formation. In cis, the insertion allele causes an increase in DSBs at site I but
      a decrease in DSBs at site II. In trans, two effects are observed. One effect
      likely reflects very early pre-DSB interhomolog interactions; the second is
      suggestive of a later, more intimate interaction in which sites I and II on the
      two homologs all compete for DSBs. The existence of interhomolog interactions in
      early meiotic prophase can explain how the sites of crossovers come to lie
      between the homolog axes at pachytene.

PMID- 7588642
TI  - Primer RNA synthesis by plasmid-specified Rep protein for initiation of ColE2 DNA
      replication.
AB  - Initiation of in vitro ColE2 DNA replication requires the plasmid-specified Rep
      protein and DNA polymerase I but not RNA polymerase and DnaG primase. The ColE2
      Rep protein binds specifically to the origin where replication initiates. Leading
      strand synthesis initiates at a unique site in the origin and lagging-strand DNA
      synthesis terminates at another unique site in the origin. Here we show that the
      primer RNA for leading-strand synthesis at the origin has a unique structure of
      5'-ppApGpA. We reconstituted the initiation reaction of leading-strand DNA
      synthesis by using purified proteins, the ColE2 Rep protein, Escherichia coli DNA
      polymerase I and SSB, and we showed that the ColE2 Rep protein is a priming
      enzyme, primase, which is specific for the ColE2 origin. The ColE2 Rep protein is
      unique among other primases in that it recognizes the origin region and
      synthesizes the primer RNA at a fixed site in the origin region. Specific
      requirement for ADP as a substrate and its direct incorporation into the 5' end
      of the primer RNA are also unique properties of the ColE2 Rep protein.

PMID- 7588644
TI  - Reconsideration of the genetic risk assessment for ethylene oxide exposures.
AB  - The US Environmental Protection Agency (EPA) developed a genetic risk assessment
      model for exposures to ethylene oxide utilizing data on the induction of
      reciprocal translocations in male germ cells [Rhomberg et al. 1990]. This
      particular approach served as a reasonable initial attempt, albeit somewhat
      limited with regard to endpoint and only partially attentive to the mechanisms of
      induction of genetic alterations and the behavior of chromosomes during meiosis.
      The present paper discusses the scientific basis for a reassessment of the EPA
      model, providing data and hypotheses related to effective dose to the target
      cells and shape of the dose-response relationship at low doses, and dose rates.
      While the present genetic risk assessment approach is discussed in terms of
      ethylene oxide, it would be applicable to most mutagenic chemicals. The outcome
      of the discussion is that the genetic risk for exposed males from reciprocal
      translocation induction will be negligible at low doses since the dose-response
      curve is likely to be a function of the square of the dose. In addition, the
      proportion of genetically unbalanced live born offspring in humans arising from
      reciprocal translocation carriers is less than 10% of the frequency formed
      through meiotic segregation and fertilization for such carriers. Simply from a
      consideration of mechanism--namely, the very high probability of DNA repair prior
      to the next S-phase for a resting oocyte--it would be predicted that there would
      be a very low to negligible frequency of translocations in female germ cells from
      ethylene oxide exposure. It is further stressed that additional components of a
      genetic risk model require a consideration of all germ cell stages in the male,
      and the inclusion of calculations for point and deletion mutations. Some
      indications of likely response are presented with these points in mind.

PMID- 7588645
TI  - Sensitivity of somatic mutations in human umbilical cord blood to maternal
      environments.
AB  - To assess the potential effect of maternal environments on human embryonic/fetal
      somatic mutation, we measured the frequencies of hypoxanthine-guanine
      phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (Mf), and
      glycophorin A (GPA) variant erythrocytes (Vf) of both allele-loss (phi/N) and
      allele-loss-and-duplication (N/N) phenotypes in umbilical cord blood. The mean
      hprt Mf (1.40 +/- 1.11 x 10(-6), N = 66) and GPA Vf (phi/N 4.0 +/- 2.2 x 10(-6),
      N = 114; N/N 2.7 +/- 2.0 x 10(-6), N = 91) were significantly lower than those
      previously reported for adult populations. In addition, the hprt Mf was
      significantly higher than that of a published study of newborn cord blood samples
      from a geographically distant population (0.64 +/- 0.41 x 10(-6), N = 45, P <
      0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic
      data from these two populations led to the sampling of 10 additional newborns
      specifically matched to the published study for maternal socioeconomic status.
      The hprt Mf (0.70 +/- 0.49 x 10(-6)) of this selected population was consistent
      with the published report and significantly lower than that of our initial
      population (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These results
      indicate that there is an environmental effect related to maternal socioeconomic
      status on the frequency of embryonic/fetal somatic mutations. Molecular analyses
      of hprt mutants from this cohort with elevated Mf revealed a significant decrease
      in the relative contribution of gross structural mutations to the overall Mf (25
      of 38, 66% vs. 34 of 41, 83%, P = 0.024, chi 2 test), suggesting that the higher
      Mf resulted from an elevated level of "point" mutations. No individual maternal
      demographic or environmental factor was identified as contributing more
      significantly than other any factor to the observed variability in hprt Mf or GPA
      Vf.

PMID- 7588648
TI  - Induction of kinetochore-containing micronuclei by exogenous O6-methylguanine
      requires conversion of the methylated base to a nucleotide.
AB  - It has been reported that exogenous alkylated purines, such as O6-methylguanine
      (O6meG), induce aneuploidy in mammalian cells. It is shown here that the
      aneugenic effect of O6meG, evidenced by its ability to induce micronuclei in
      rodent cells, is dependent on its conversion to O6-methyl-guanosine-5'
      monophosphate (O6me-5'-GMP) by hypoxanthine-guanine phosphoribosyl transferase
      (HPRT). This conclusion, in contrast with previous in vitro data showing that
      O6meG does not seem to be a substrate for HPRT, was based on the following
      observations: 1) O6meG did not induce micronuclei in HPRT-deficient Chinese
      hamster cells, but did induce micronuclei in HPRT-proficient cells, and in mouse
      cells partially or totally deficient in adenine phosphoribosyl transferase; 2)
      O6meG was not metabolized in HPRT-deficient cells, while in wild-type cells a
      number of metabolites were detected by high performance liquid chromatography
      (HPLC) analysis of cold acid extracts, one of them coeluting with O6me-5'-GMP
      used as a marker; 3) when de novo synthesis of purine nucleotides was inhibited
      by aminopterin, O6meG sustained the growth of HPRT-proficient, but not of HPRT
      deficient, cells; and 4) when HPRT-deficient cells were treated with liposomes
      charged with O6me-5'-GMP, induction of micronuclei was shown. The finding that
      methylated guanine exerts its aneugenic action through methylated nucleotide(s)
      provides an important, though indirect, support to the hypothesis that alkylating
      agents may induce aneuploidy via nucleotide pool alkylation.

PMID- 7588639
TI  - Vg1 RNA binding protein mediates the association of Vg1 RNA with microtubules in
      Xenopus oocytes.
AB  - Localized RNAs are found in a variety of somatic and developing cell types. In
      many cases, microtubules have been implicated as playing a role in facilitating
      transport of these RNAs. Here we report that Vg1 RNA, which is localized to the
      vegetal cortex of Xenopus laevis oocytes, is associated with microtubules in
      vivo. Because of the ubiquitous nature of tubulin, the association of specific
      RNAs with microtubules is likely to involve factors that recognize both RNA and
      microtubules. Vg1 RNA binding protein (Vg1 RBP), previously shown to bind with
      high affinity to the vegetal localization site in Vg1 RNA, appears to function in
      this capacity. Vg1 RBP is associated with microtubules: it is enriched in
      microtubule extracts of oocytes and is also co-precipitated by heterologous,
      polymerized tubulin. Furthermore, Vg1 RBP binding activity is required for the
      specific association of Vg1 RNA to microtubules in vitro. These data suggest a
      general model for how specific RNAs can be localized to particular sites via
      common cytoskeletal elements.

PMID- 7588649
TI  - Aflatoxin B1, 2-aminoanthracene, and 7,12-dimethylbenz[a]anthracene-induced
      frameshift mutations in human APRT.
AB  - Aflatoxin B1, 2-aminoanthracene, and 7,12-dimethylbenz[a]anthracene have been
      implicated in the etiology of human cancers. In this study, we demonstrate that
      these three chemicals can be activated by rat liver homogenate S9 coupled with
      NADPH coenzymes to produce a dose-dependent increase in the frequency of APRT
      reversion in the APRT-deficient human cell line HTD114. HTD114 contains single
      nucleotide insertions at different positions in each APRT allele and the
      spontaneous reversion frequency is < 10(-8). However, the highest reversion
      frequency induced by these chemicals is 1.2-2.0 x 10(-5), at least a 10(3)-fold
      increase over the frequency of spontaneous reversion. Reversion of either mutant
      allele was observed to be a consequence of a frame-restoring loss of a single
      nucleotide, which indicates that these three chemicals can function as frameshift
      mutagens in human cells.

PMID- 7588646
TI  - Analysis of point mutations in the hprt gene of cancer patients treated with
      radioimmunoglobulin therapy.
AB  - The mutagenic impact of various environmental and therapeutic agents can now be
      directly assayed in humans by the T-lymphocyte cloning assay. We have previously
      reported that following radioimmunoglobulin therapy, cancer patients exhibited
      increased mutant frequency of the hprt locus and an increased yield of large
      intergenic deletions compared to unexposed controls. Here we report the results
      of the analysis of 26 independent hprt mutations in nine cancer patients who
      underwent radioimmunoglobulin therapy. The majority of mutations (52%) had lost
      exon sequences from the mRNA. The remaining mutations were 20% small deletions
      and frameshifts and 28% base substitutions. The type of mutations observed were
      similar to those seen in unexposed controls. The site distribution of the
      mutations, however, indicates that some sequence contexts may be more sensitive
      to radiation mutagenesis than others.

PMID- 7588647
TI  - DNA sequence analysis of spontaneous hprt mutations arising in vivo in cynomolgus
      monkey T-lymphocytes.
AB  - To study the mechanisms of mutagenesis in vivo, we analyzed mutations at the
      hypoxanthine phosphoribosyl transferase (hprt) locus using cDNA from cynomolgus
      monkey T-lymphocytes. In the present study, the spectrum of spontaneous hprt
      mutations arising in vivo in wild-caught cynomolgus monkey peripheral T
      lymphocytes is described. Cells were isolated from peripheral blood, and mutant
      clones were selected in 6-thioguanine, propagated, and stored frozen. cDNA was
      copied from hprt mRNA from a lysate of 7,000 to 20,000 cells. A 780-base-pairs
      (bp) region including the coding region was amplified by polymerase chain
      reaction and directly sequenced. We sequenced 40 spontaneous mutants from 11
      monkeys. Of these 40 clones, 23 (57%) had base-pair substitutions, 11 (28%) had
      small (< 20 bp) deletions and/or insertions, and 6 (15%) had large (> 20 bp)
      deletions and/or insertions. Of the 23 base substitutions, 13 were transitions
      (11 G:C-->A:T, 1 A:T-->G:C, and 1 tandem TT-->CC) and 10 were transversions (3
      G:C-->T:A, 3 G:C-->C:G, 2 A:T-->T:A, 2 A:T-->C:G). Bases 209 and 617 were
      apparent substitution hotspots, which have also been observed as hotspots in
      human hprt. In 2 clones with large insertions, the inserted bases were of
      intronic origin. One of these lost 272 bp from exons 2-3 and contained a 93-bp
      insertion from the middle of intron 3. Two clones with small deletions and 5
      clones with large deletions or insertions (7/40 or 17.5%) could be splice
      mutants.

PMID- 7588650
TI  - Evaluation of the micronucleus test in vitro using Chinese hamster cells: results
      of four chemicals weakly positive in the in vivo micronucleus test.
AB  - A rapid and simple procedure for the micronucleus test (MNT) in vitro using
      Chinese hamster ovary (CHO) cells was established in our laboratory. The assay is
      intended to quickly screen chromosomal aberrations in vitro within the framework
      of industrial genotoxicity studies. To test the sensitivity of the assay in the
      experiments described here, four substances, classified as noncarcinogens but
      reported as weak inducers of micronuclei (MN) in bone-marrow cells of mice, were
      evaluated in the MNT in vitro. Of the four compounds, ascorbic acid, phenol, and
      2,6-diaminotoluene proved to be genotoxic in the MNT in vitro. Titanium dioxide,
      which could not be dissolved in the culture medium, did not induce MN. The MNT in
      vitro proved to be quick and relatively simple and to yield highly reproducible
      results when testing the four chemicals.

PMID- 7588652
TI  - An examination of the potential "genotoxic" carcinogenicity of a biopesticide
      derived from the neem tree.
AB  - Structural analyses of azadirachtin, a promising biopesticide recently introduced
      into the United States, indicates that this natural product has the potential for
      acting as a "genotoxic" carcinogen. In view of the fact that genotoxic
      carcinogens are regarded as presenting a potential carcinogenic risk to humans,
      the present finding suggests that the possible metabolism of azadirachtin to DNA
      reactive products be evaluated experimentally.

PMID- 7588651
TI  - Taurine and ellagic acid: two differently-acting natural antioxidants.
AB  - Naturally occurring antimutagenic compounds are extensively analyzed for their
      capacity to protect cells from induced damage. We selected two agents, taurine
      and ellagic acid, treated in the literature as antioxidants, but whose activity
      is insufficiently known. This paper reports on the ability of these agents to act
      against damage induced by mitomycin-C and hydrogen peroxide in Chinese hamster
      ovary cells cultivated in vitro. Cytogenetic and cytofluorimetric analyses were
      performed. Ellagic acid proved to have more than one mechanism of action,
      probably as a scavenger of oxygen species produced by H2O2 treatment, and as a
      protector of the DNA double helix from alkylating agent injury. In our
      experimental conditions, taurine seems able to scavenge oxygen species.

PMID- 7588655
TI  - Causes of visual impairment in central Ethiopia.
AB  - A survey conducted on a stable, mainly rural population of 60,820 in Central
      Ethiopia revealed an overall blindness prevalence of 1.1%. A follow up study was
      carried out to accurately determine the etiologies and causes of visual loss and
      impairment. A detailed ophthalmic evaluation was done on 523 out of 872
      individuals identified as being visually impaired. The results showed that 194
      (37%) were blind (Categories 3, 4, and 5 = maximum visual acuity less than 3/60
      in the better eye). One hundred and seven (21%) (Categories 1 & 2 = maximum
      visual acuity better than 3/60 to less than 6/18 in the better eye using the WHO
      categories of visual impairment). The rest 222 (43%) were blind in one eye only.
      The commonest anatomical cause of blindness is corneal (32%). Cataract (25%),
      atrophied globe(s) (20%) and glaucoma (17%) follow as the other leading causes.
      Trachoma (35%), degenerative conditions (35%) and other infections (9%) were the
      major etiologies of blindness. Similar pattern of anatomical causation was
      observed in those classified under categories of visual impairment 1 and 2,
      referred to as "low vision". The most important etiologies of low vision were
      trachoma (30%), degenerative (24%), trauma (13%) and other infections (8%).
      Trauma was the most important etiology of monocular blindness (39%). Blindness
      was either preventable or curable in 74% of the cases.

PMID- 7588654
TI  - Cigarette smoking, eating behaviour, blood haematocrit level and body mass index.
AB  - This study is designed to evaluate the effects of smoking on dietary habits
      including tea, coffee and alcohol intake; and to also evaluate haematocrit level
      and body mass index changes in smokers. Cross-sectional type of investigation
      based on a questionnaire was applied to the healthy subjects and cluster
      stratified and random sampling methods were used to select the subjects from five
      health stations. Male and female groups were evaluated separately. Blood
      haematocrit levels of smokers were found to be significantly higher than that of
      non-smokers (p < 0.001) in both sexes. Smokers were found to consume more
      alcohol, coffee, saturated fat than non-smokers (p < 0.05-p < 0.0001). Smoker
      women consumed more tea (p < 0.0001) and less red and white meat (p < 0.05) than
      non-smoker women. Smokers were found to consume fewer green vegetables and fruits
      than non-smokers in both sexes (p < 0.05-p < 0.0001). Additionally, body mass
      index was found higher in the 25 or more cigarette smokers a day (p < 0.01) when
      compared to the non-smokers regardless of sex. These data suggest that high
      cancer risk and coronary heart diseases associated with smoking may be compounded
      by somewhat lower intake of foods which are thought to be cancer protective.

PMID- 7588657
TI  - Post menopausal vaginal bleeding due to vaginal wall leech infestation.
AB  - A 50 year old para vi patient was referred to Mekelle Hospital on October 23,
      1992 with post menopausal vaginal bleeding and haemorrhagic shock to rule out
      endometrial carcinoma. She was anaemic. Speculum examination revealed a darkish
      mass attached to the posterior vaginal fornix. The mass was instilled with about
      5 ml (1%) Lidocaine, after which it detached itself and started movement. The
      mass was an aquatic leech. Previously, post menopausal vaginal bleeding due to
      leech infestation was not reported, and therefore, this has to be included in the
      differential diagnosis of abnormal vaginal bleeding. Emphasis should also be made
      to create awareness among professionals working in areas where leech infestation
      is prevalent.

PMID- 7588653
TI  - Clinico-epidemiological study of lymphatic filariasis southwestern Ethiopia.
AB  - Clinical and parasitological night blood surveys have been carried out for
      lymphatic filariasis in people living in two communities adjacent to the Baro
      River, near the town of Gambella in 1993. The survey covered more than 90% of the
      population in Tektak and Ketch. Inhabitants were registered and detailed
      information on prevalence, and intensity of microfilaremia and clinical symptoms
      was obtained. The overall microfilaria prevalence, using the counter chamber
      technique, was 20.7% with males and females showing microfilaria rates of 23.7%
      and 18.5%, respectively. Infection densities varied between 40 and 1540
      microfilariae (mf) per ml of blood among the infected, giving a geometric mean
      intensity of 309 mf/ml of blood which was much more pronounced in females than in
      males. In males, 20.3% had hydrocoele and this condition was noted above the age
      of 35. About 40% of those with hydrocoele had microfilaremia. Groin gland
      enlargement was recorded in 40.0% of the examined. No case of elephantiasis was
      encountered. This disease has not received much attention in Ethiopia. The
      possible reasons will be discussed in connection with the results of this study.

PMID- 7588658
TI  - Macrodystrophia lipomatosa. A case report.
AB  - Macrodystrophia lipomatosa, a rare form of localized gigantism of unknown cause,
      is characterized by a dramatic overgrowth of all the mesenchymal elements,
      particularly the fibroadipose tissue, of one or more digits of the foot or hand.
      Of the known forms, static and progressive (1), we report the case of an African
      patient, of Bantu origin, who had a progressive deformity of his left hand.

PMID- 7588659
TI  - Seeking an appropriate and low cost diagnostic method for intestinal
      schistosomiasis.

PMID- 7588656
TI  - Breech delivery and foetal outcome: a review of 291 cases.
AB  - In a three year period (September 1989 to August 1992), among 7,170 consecutive
      deliveries at Yekatit 12 Hospital, Addis Abeba, Ethiopia, there were 291
      singleton breech deliveries with a 4% incidence rate at a gestational age of 28
      weeks and above. In 28% and 57% of the infants, weight was below 2,500 grams and
      Apgar score was less than 7 in the first minute, respectively. The gross
      perinatal mortality rate for breech delivery in the first 24 hours was 330 per
      1,000 deliveries, which was significantly higher than for the total number of
      deliveries (70 per 1,000; p < 0.001). However, the perinatal mortality rate was
      1,000 per 1,000 deliveries for foetuses of less than 1,500 grams, 635 for
      foetuses between 1,500-2,500 grams, and 156 for foetuses of greater than 2,500
      gm. In general, foetuses with low birth weight showed a high mortality rate (p <
      0.001). There was also a two-fold increase in perinatal death in patients without
      antenatal care (p < 0.001). In order to reduce this unacceptably high perinatal
      mortality, emphasis must be given to appropriate training of physicians and
      midwives in the management of breech deliveries along with provisions of
      efficient prenatal care to improve birth weight. In addition, as most of the
      neonatal problems are preventable, measures need to be taken to establish
      neonatal units equipped with basic resuscitation materials and manpower.

PMID- 7588660
TI  - The orthogonal two-needle technique: a new axillary approach to the brachial
      plexus.
AB  - Ninety-eight patients scheduled for elbow, forearm, wrist or hand surgery were
      allocated randomly to one of two different techniques of brachial plexus block,
      both using the axillary approach. The blocks were all performed at the level of
      the insertion of the lateral margin of the pectoralis major muscle on the
      humerus. The same mixture and volume of anaesthetic solution (30 mL of a mixture
      of equal parts of 0.5% bupivacaine with adrenaline 1:200 000 and 2% lignocaine)
      was injected through two needles positioned above and below the axillary artery,
      in the fascial compartments containing the median and ulnar nerves, respectively.
      Confirmation of correct needle placement was obtained by elicitation of
      paraesthesias. In one group of patients (n = 40) the needles were inserted
      parallel to the axillary artery pathway and the anaesthetic solution was injected
      toward the apex of the axilla. In a second group (n = 58) the needles were
      inserted orthogonally with respect to the neurovascular bundle pathway, aimed
      towards the posterior fascial compartment containing the radial nerve. Using the
      second technique, all the terminal branches of the brachial plexus were more
      frequently involved in the block, including the distribution of the
      musculocutaneous nerve. It seems likely that the inclination of the needles
      causes a preferential spread of the anaesthetic solution which follows the
      direction of the needle shaft.

PMID- 7588661
TI  - Safety and effectiveness of an oral premedication regimen before cardiac surgery.
AB  - Thirty-five adult cardiac surgical patients received 20 mg dipotassium
      clorazepate orally the evening before surgery and 2 mg flunitrazepam 60 min
      before induction of anaesthesia. If anaesthesia was to be induced after 08.30
      hours patients received an additional 20 mg dipotassium clorazepate at 06.15
      hours. The following measurements were made: peripheral arterial oxygen
      saturation (Spo2) breathing room air; anxiety by visual analogue scale; degree of
      sedation; and haemodynamic variables. Mean (Spo2) was 95.9% (SD 1.8%) on the day
      before surgery and 95.4% (SD 1.5%) on arrival at the operating room. When the
      operation started after 08.30 hours, mean (Spo2) at 09.00 hours was 96.0% (SD
      1.4%). There were no detected episodes of hypoxaemia after premedication. Mean
      anxiety score decreased significantly from 3.9 (SD 2.6) on the day before surgery
      to 3.3 (SD 2.1) on arrival at the operating room (patients' score; P < 0.002) and
      from 4.6 (SD 2.4) to 3.3 (SD 2.0) (anaesthesiologists' score; P < 0.001). Nearly
      all patients were considered well sedated, which was reflected by normal
      haemodynamic variables on arrival at the operating room. The combination of
      clorazepate and flunitrazepam is effective oral premedication for adult cardiac
      surgery, causing no obvious desaturation even when supplemental oxygen is not
      given.

PMID- 7588662
TI  - A comparison of intravenous and inhalational maintenance anaesthesia for
      endoscopic procedures in the aspirin intolerance syndrome.
AB  - Intravenous (n = 21) and inhalational maintenance anaesthesia (n = 21) were
      compared by random allocation in patients with the aspirin intolerance syndrome
      undergoing endoscopic nasal procedures. Premedication was with oral midazolam and
      intravenous methylprednisolone sodium succinate 10 mg kg-1. Anaesthesia was
      induced in both groups with etomidate and alfentanil and ventilation was
      controlled. Anaesthesia was maintained in the intravenous group by infusion of
      alfentanil 1-1.5 micrograms kg-1 min-1 and injections of midazolam 2.5-5 mg h-1,
      and in the inhalational group by isoflurane up to 2%. Moderate arterial
      hypotension (70 mmHg) was achieved with nitroglycerine 0.5-5 micrograms kg-1 min
      1 in the intravenous group, and with isoflurane up to 2% in the inhalational
      group. Adrenaline 1: 200 000 with 2% lignocaine was injected into the operative
      field. One patient in the inhalational group developed a resistant
      tachyarrhythmia but there was no overall significant difference (P = 0.34) in the
      frequency of dysrhythmias precipitated by adrenaline and lignocaine between the
      two groups. In one patient of each group methylprednisolone precipitated
      bronchospasm. On later challenge testing, 125 mg of intravenous
      methylprednisolone significantly reduced the peak expiratory flow (P < 0.05) in
      one of these patients. The results suggest that intravenous and inhalational
      maintenance anaesthesia are equally suitable for patients with aspirin
      intolerance syndrome. Corticosteroids during surgery should be given by the same
      route used pre-operatively (spray, oral, or spray plus oral) because intravenous
      injection may have adverse effects.

PMID- 7588663
TI  - The effects of propofol on laryngeal reactivity and the haemodynamic response to
      laryngeal mask insertion.
AB  - The ease of the insertion of laryngeal mask and the haemodynamic response were
      assessed 2 min after induction of anaesthesia with either propofol 2.5 mg kg-1 or
      thiopentone 4.0 mg kg-1 in 38 ASA I premedicated patients. The inserting
      conditions scored as excellent, good, poor and unable to insert were
      significantly better with propofol than with thiopentone (P < 0.001). Insertion
      of the laryngeal mask was followed by a transient but significant increase in
      both systolic (P < 0.05) and diastolic (P < 0.01) arterial pressure in the
      thiopentone group; there was no comparable response in the propofol group. The
      heart rate varied little from baseline in both groups.

PMID- 7588664
TI  - The laryngeal mask airway for awake diagnostic bronchoscopy. A retrospective
      study of 200 consecutive patients.
AB  - The laryngeal mask airway (LMA) provides a view of the larynx and moving vocal
      cords without loss of airway control and can be used in flexible fibreoptic
      bronchoscopy for both anaesthetized and awake patients. In this retrospective
      review of 200 consecutive patients over a 30 month period, bronchoscopy was
      successful via the LMA in all but one patient using a technique of topical
      anaesthesia and sedation. The LMA directs the fibrescope to the glottis, allows
      respiratory function to be monitored and oxygen to be given. Complication rates
      were similar to those reported for transnasal awake bronchoscopy. Insertion of
      the LMA in the awake fasted patient is safe and easily achieved.

PMID- 7588665
TI  - Failure rate of epidural anaesthesia for foot and ankle surgery. A comparison
      with other surgical procedures.
AB  - To test whether epidural anaesthesia for foot and ankle surgery is associated
      with an unacceptably high incidence of inadequate surgical analgesia, we
      prospectively compared two groups of patients, one undergoing foot or ankle
      surgery (160 patients) and the other surgical procedures not performed in areas
      innervated by L5-S1 ( (168 patients). Lumbar epidural anaesthesia was performed
      in both groups by administering carbonated lignocaine 2% with adrenaline
      1:200000. Seven patients in the foot-ankle group (4.4%) and 10 in the group for
      comparison (5.9%) exhibited inadequate surgical analgesia. This difference is not
      statistically significant. Within the foot-ankle group, a significantly lower
      dose of local anaesthetic per spinal segment had been given to patients who
      displayed inadequate analgesia, compared with those who exhibited satisfactory
      analgesia (P < 0.05).

PMID- 7588666
TI  - The post-operative analgesic action of midazolam following epidural
      administration.
AB  - To study post-operative analgesia with epidural midazolam, 30 patients who had
      undergone upper abdominal surgery were divided into two equal groups. When
      patients complained of pain, they were given either 6 microliters 0.25%
      bupivacaine (control group) or 6 microliters 0.25% bupivacaine + 0.05 mg kg-1
      midazolam (midazolam group) epidurally at a single level between T7 and T12.
      Blood pressure and heart rate were similar in the two groups. Sedation was
      significantly greater in the midazolam group 10 min after administration. The
      area of analgesia was significantly larger in the midazolam group 10 and 30 min
      after administration and involved the entire spinal area and the head and face 10
      min after administration in six patients. Amnesia was observed in 14 patients in
      the midazolam group but in only one in the control group. Epidural midazolam
      together with bupivacaine adds central analgesic, sedative, and amnesic effects
      to spinal analgesia and is useful for managing post-operative pain.

PMID- 7588668
TI  - A general anaesthesia service for magnetic resonance imaging.
AB  - A general anaesthesia service for magnetic resonance scanning is described and
      figures for scans under general anaesthesia for the past 5 years are presented
      together with a description of the anaesthesia service related to the
      environment, the equipment and the techniques employed. The involvement of a
      representative from the department of anaesthesia is necessary in the design of
      scanner suites if general anaesthesia services are to be provided, as they will
      almost certainly need to be. The revenue costs of such a service are also briefly
      considered.

PMID- 7588667
TI  - The PIO2 vs. SpO2 diagram: a non-invasive measure of pulmonary oxygen exchange.
AB  - A non-invasive method for measuring pulmonary oxygen exchange is described using
      a plot of inspired oxygen partial pressure (PIO2) vs. oxygen saturation (SpO2).
      This method was assessed using nine normal subjects and 35 patients undergoing
      major surgery, including five thoracotomies. In each patient PIO2 was varied to
      produce a range of values of SpO2 between 85% and 99%. A model based on the
      inspired to arterial oxygen difference involving the shunt equation, solved by
      simultaneous numerical methods, was used to show how the PIO2 vs. SaO2
      relationship could be used to derive two parameters of oxygen exchange, the PIO2
      Pco2 difference and the Virtual Shunt. The model allows the inspired to arterial
      difference in PO2 to be divided into (a) an inspired to 'ideal' alveolar
      difference attributable to the balance between alveolar ventilation and oxygen
      uptake; (b) an 'ideal' alveolar to end-capillary difference attributable to
      inhomogeneity in ventilation/perfusion ratios; and (c) end-capillary to arterial
      difference attributable to true shunt, which was termed 'virtual shunt' because
      of the uncertainties of assuming fixed values for haemoglobin concentration and
      arteriovenous oxygen content difference. The coefficient of determination showed
      that there was a good fit of the model to the data. Because the method is model
      based it enables extrapolation to different PIO2 values as well as the study of
      the evolution of changes in gas exchange under varying conditions.

PMID- 7588669
TI  - Comparison of glucose and sucrose as an indicator for dilution volumetry in
      haemorrhagic shock.
AB  - A new technique for dilution volumetry using glucose as an indicator is proposed.
      The initial distribution volume of glucose (Vdgluc) was calculated in 11 adult
      mongrel dogs using a one-compartment model, and Vdgluc was then compared with the
      initial distribution volume of sucrose (Vdsucr), which is less metabolized.
      Insulin concentrations in the plasma were measured to calculate the insulinogenic
      index. The Vdgluc and the Vdsucr at baseline and after induced haemorrhagic shock
      (30 mL kg-1) were calculated. There was a significant correlation (r = 0.84, n =
      22, P < 0.001) between Vdgluc and Vdsucr, but not between Vdgluc and the
      insulinogenic index. The limits of agreement ( +/- 2SD) between the two methods
      were +0.32 to -0.08L. Vdgluc indicates the volume of the central compartment, but
      cannot replace Vdsucr for clinical purposes. Glucose can be used repeatedly as an
      indicator for easy and safe dilution volumetry in vivo.

PMID- 7588670
TI  - Peri-operative administration of rectal diclofenac sodium. The effect on renal
      function in patients undergoing minor orthopaedic surgery.
AB  - In a randomized, double-blind study, we administered placebo and diclofenac
      sodium 100 mg suppositories 1 h pre-operatively and on the first post-operative
      morning to 22 adult patients undergoing minor orthopaedic surgery. A standardized
      post-operative intravenous fluid regimen was instituted until oral fluids were
      tolerated. Renal function was assessed pre-operatively, and on the first and
      second post-operative days by the measurement of urine output, creatinine, urea,
      sodium, potassium and NAG (N-acetyl-b-D-glucosaminidase) levels and serum
      creatinine, urea, sodium and potassium concentrations. On the first post
      operative day, the diclofenac group demonstrated a reduced urinary sodium
      excretion. On the second post-operative day, a reduced urinary NAG/creatinine
      ratio was observed in the diclofenac group when compared to placebo. We conclude
      that peri-operative administration of diclofenac causes changes in renal function
      consistent with prostaglandin inhibition on the first post-operative day but had
      no lasting adverse effects in this group of patients. Our results reinforce the
      need for caution when administering this drug in the context of pre-existing
      renal impairment.

PMID- 7588673
TI  - Haemorrhage during anaesthesia and surgery: continuous measurement of
      microcirculatory blood flow in the kidney, liver, skin and skeletal muscle.
AB  - Multichannel laser Doppler flowmeters allow continuous, simultaneous measurement
      of perfusion in several organs. We measured microcirculatory blood flow in the
      kidney, liver, skin and skeletal muscle in 10 anaesthetized rats subjected to
      abdominal surgery and graded haemorrhage (withdrawal of 5% total blood volume
      every 10 min). Mean arterial blood pressure, heart rate and haemoglobin
      concentrations were also measured. Muscle blood flow decreased after only 10%
      blood loss, but without significant changes in the other organs. At this time the
      perfusion signal from the muscle was cycling 2-3 times per min (slow wave
      flowmotion) which was never seen in any other organ. After 35% blood loss, all
      organs monitored maintained approximately 70% of initial flow, despite a 45%
      decrease in mean arterial pressure from 104 +/- 12 to 55 +/- 9 mmHg (mean +/-
      SD). After 40% blood loss there was a sharp decrease in blood flow in all organs.
      Haemoglobin concentration decreased from 14.4 +/- 0.8 to 10.8 +/- 1.3 mg dL-1
      after 45% blood loss. We conclude that laser Doppler flowmetry is useful for
      continuous measurement of microcirculatory blood flow in several organs
      simultaneously during haemorrhagic hypovolaemia. It showed that microcirculatory
      blood flow in skeletal muscle is particularly sensitive to lesser degrees of
      blood loss during anaesthesia. Hypovolaemia-induced slow wave flowmotion occurred
      only in skeletal muscle, which may be linked to fluid mobilization during
      haemorrhage.

PMID- 7588672
TI  - Effects of prostaglandin E1 on intra-operative central and peripheral
      temperatures during upper abdominal surgery.
AB  - Effects of prostaglandin E1 (PGE1) on temperatures during upper abdominal surgery
      under isoflurane anaesthesia were studied. Forty-five patients were randomly
      assigned to one of three groups (15 patients per group). One group received 0.05
      micrograms kg-1 min-1 of PGE1, the second group received 0.1 microgram kg-1 min-1
      of PGE1 just after the induction of anaesthesia, and the third group received no
      PGE1 during anaesthesia (control). Tympanic membrane (central) temperatures,
      forearm temperatures, and fingertip temperatures were recorded during surgery
      every 30 min. Tympanic membrane temperatures in the 0.05 micrograms kg-1 min-1
      group during and at the end of surgery were significantly higher than those in
      the control group. In the 0.1 microgram kg-1 min-1 group, maximum decrease of
      tympanic membrane temperature was significantly larger than that in the control
      group. Fingertip temperatures in the 0.05 micrograms kg-1 min-1 group during
      surgery were significantly higher than those in the control group. This result
      suggests that 0.05 micrograms kg-1 min-1 of PGE1 may be superior to 0.1 microgram
      kg-1 min-1 of PGE1 for maintaining central and peripheral temperatures during
      surgery and general anaesthesia.

PMID- 7588671
TI  - EEG analysis and pharmacodynamic modelling after intravenous bolus injection of
      eltanolone (pregnanolone).
AB  - An intravenous bolus dose of 0.75 mg Kg-1 eltanolone emulsion was administered to
      18 unpremedicated ASA I or II patients. In addition to clinical observation and
      haemodynamic monitoring, EEG power spectrum and median frequency were recorded.
      Venous blood was collected to establish a concentration-effect relation using the
      median frequency as a pharmacodynamic parameter for hypnotic effect, and with
      analysis of data with the sigmoidal Emax model. Emax was determined as the
      maximal decrease of the median frequency caused by the CNS depressant effect of
      eltanolone. The results of seven of 15 patients with complete serum and EEG
      analysis could be described by a sigmoidal curve. The calculated IC50, the serum
      concentration producing 50% inhibition of Emax, was 0.57 micrograms mL-1. Median
      frequency occasionally decreased independently of eltanolone serum concentration
      in seven patients because interference by natural sleep was not prevented before
      induction or during awakening by setting continuous stimulations. In relation to
      the peak serum concentration, the decrease in median frequency occurred late in
      one patient. Nevertheless, the present study provides a preliminary estimation of
      the IC50 of eltanolone. From the clinical point of view, eltanolone showed
      satisfactory induction characteristics which warrant further evaluation.

PMID- 7588675
TI  - Three-way tap for identifying the epidural space.

PMID- 7588674
TI  - Life-threatening transurethral resection syndrome despite monitoring of fluid
      absorption with ethanol.
AB  - Ethanol monitoring is a fairly new method for assessing fluid absorption during
      transurethral resection of the prostate. The volume of irrigant absorbed is
      usually estimated from a nomogram every 10 min during the operation. We report a
      case in which a patient developed a transurethral resection syndrome and
      circulatory shock despite ethanol monitoring and adequate volume replacement. The
      further course of the operation showed that absorption had occurred by the
      extravascular route. In these cases, ethanol monitoring can be misleading as the
      maximum breath ethanol level occurs after a delay of 20 min and the fluid
      absorption is three times larger than indicated by the nomogram.

PMID- 7588676
TI  - The mechanical effects of contractions on blood flow to the muscle.
AB  - To determine whether muscle contractions can increase muscle blood flow
      independently from metabolic factors, we isolated the vasculature of the left
      diaphragm or gastrocnemius muscle of anesthetized and mechanically ventilated
      dogs. Arterial blood flow was controlled with a constant pressure source and the
      arterial pressure (Pa) was decreased in steps to obtain pressure-flow
      relationships (P-Q). The local vasculatures were maximally dilated with
      nitroprusside [mean (SD) 114.0 (32.0) micrograms.min-1], adenosine [1.43 (0.41)
      mmol.l-1.min-1], and acetylcholine [1.43 (0.41) mmol.l-1.min-1] and the P-Q with
      and without spontaneous contractions (n = 6), stimulated twitches (n = 12, 2-4
      Hz), or tetanic trains (n = 7, 25 Hz) in the diaphragm and stimulated twitches (n
      = 6, 2-4 Hz), or tetanic contractions (n = 6, 12-16 trains) in the gastrocnemius
      were compared. The pressure axis intercept decreased (P < 0.5) with spontaneous
      contractions in the diaphragm and the slope did not change. At Pa of 13.3 kPa,
      flow increased from 36.2 (34.9) to 43.9 (38.2) ml.min-1.100 g-1 (P < 0.05).
      During twitch contractions, the slope and intercept of the P-Q were not
      significantly different from vasodilatation alone, but the flow at a pressure of
      13.3 kPa increased slightly. In the gastrocnemius (n = 6), continuous and
      intermittent tetanic contractions did not affect P-Q or flow at Pa of 100 mmHg (n
      = 6). Furthermore, increasing venous pressure to 6.7 kPa did not affect flow in
      this muscle. We conclude that the muscle pump has only a small direct effect on
      muscle blood flow and its main effect is to reduce venous pressures.

PMID- 7588677
TI  - Changes in the electromyographic spectrum power distribution caused by a
      progressive increase in the force level.
AB  - The purpose of the present study was to determine the specific changes occurring
      in the power spectrum with an increasing force level during isometric
      contractions. Surface electromyographic signals of the triceps brachii (TB) and
      the anconeus (AN) of 29 normal subjects were recorded during isometric ramp
      contractions performed from 0 to 100% of the maximum voluntary contraction (MVC)
      in a 5-s period. Power spectra were obtained at 10, 20, 30, 40, 50, 60, 70, 80
      and 90% MVC. Changes in the shape of these spectra were evaluated visually and
      with the calculation of several statistical parameters related to the
      distribution of power along the frequency axis, such as median frequency and mean
      power frequency, standard deviation, skewness, first and third quartiles and half
      power range. For the AN, the behaviour of the spectrum was relatively similar
      across subjects, presenting a shift toward higher frequencies without any major
      change in the shape of the spectrum. For the TB, subjects with a thin skinfold
      thickness presented similar behaviours. In subjects with a thicker skinfold,
      however, a loss of power in the high frequency region paralleled the increase in
      the force level. Significant correlations were obtained between the extent of the
      change in the value of higher order statistical parameters across force and the
      thickness of the skin. This points out the importance of the skinfold layer when
      recording with surface electrodes. Furthermore, the use of a combination of
      several parameters appears to provide a better appreciation of the changes
      occurring in the spectrum than any single parameter taken alone.

PMID- 7588678
TI  - Endurance time characteristics of human ankle dorsiflexors and plantarflexors.
AB  - The endurance time provides a convenient means to assess muscle fatigue
      resistance. The purpose of the experiments was to study endurance time
      characteristics of human ankle dorsiflexion and plantarflexion as a function of
      level of contraction. Nine subjects (four men, five women) were examined. The
      experimental protocol consisted of determining each individual maximum voluntary
      contraction (MVC) before each fatiguing experiment and undertaking only one
      fatiguing isometric contraction (dorsiflexion or plantarflexion) per day. Each
      subject produced at least six plantarflexion and six dorsiflexion contractions
      chosen from 15% to 90% MVC. An exponential model was fit to data for each
      individual and was then fit to the pooled data. The variance accounted for was
      over 99% for both dorsiflexion and plantarflexion mean values. As expected,
      endurance time declined as the contraction level increased. Plantarflexing
      responses presented a higher variation from subject to subject than for
      dorsiflexing. Inter-subject variability primarily seemed to involve a change in
      the shape of the endurance curve rather than a shift of the curve. When the data
      were pooled, the exponential curve had parameters similar to the average of the
      individual fits. Human ankle dorsiflexion and plantarflexion endurance times as a
      function of level of contraction were found to be similar under the present
      experimental conditions.

PMID- 7588679
TI  - Electromyographic fatigue thresholds of the superficial muscles of the quadriceps
      femoris.
AB  - The purpose of this investigation was to compare the thresholds of neuromuscular
      fatigue determined simultaneously from the vastus lateralis (VL), vastus medialis
      (VM) and rectus femoris (RF) muscles using the electromyographic fatigue
      threshold (EMGFT) test. Eight adult volunteers [mean (SD) age, 33 (10) years]
      served as subjects for this investigation. The results of a one-way repeated
      measured ANOVA indicated that there was a significant (P < 0.05) difference among
      the mean EMGFT values for the VL [248(31)W], VM [223(43)W] and RF [220(30)W]
      muscles. Tukey post-hoc comparisons indicated that the EMGFT for the RF was
      significantly (P < 0.05) lower than that of the VL. These findings suggested that
      during cycle ergometry there is a dissociation in neuromuscular fatigue
      characteristics of the superficial muscles of the quadriceps femoris group.

PMID- 7588683
TI  - Water ingestion does not improve 1-h cycling performance in moderate ambient
      temperatures.
AB  - Eight endurance-trained cyclists rode as far as possible in 1 h on a stationary
      cycle simulator in a moderate environment (20 degrees C, 60% relative humidity, 3
      m.s-1 wind speed) while randomly receiving either no fluid (NF) or attempting to
      replace their approximate 1.71 sweat loss measured in a previous 1-h
      familiarisation performance ride at approximately 85% of peak oxygen uptake with
      artificially sweetened, coloured water (F). During F, the cyclists drank mean
      1.49 (SEM 0.14) 1 of which mean 0.27 (SEM 0.08) 1 remained in the stomach at the
      end of exercise and mean 0.20 (SEM 0.05) 1 was urinated after the trial. Thus,
      only mean 1.02 (SEM 0.12) 1 of the ingested fluid was available to replace sweat
      losses during the 1-h performance ride. That fluid decreased the mean average
      heart rate from 166 (SEM 3) to 157 (SEM 5) beats.min-1 (P < 0.0001) and reduced
      the final mean serum [Na+] and osmolalities from 143 (SEM 0.6) to 139 (SEM 0.6)
      matom.l-1 (P < 0.005) and from 294 (SEM 1.7) to 290 (SEM 1.9) mosmol.l-1 (P =
      0.05), respectively. Fluid ingestion did not significantly attenuate rises in
      plasma anti-diuretic hormone and angiotensin concentrations, or decrease the
      approximate-15% falls in estimated plasma volume in the F and NF trials. Nor did
      fluid ingestion significantly affect the approximate 1.71.h-1 sweat rates, the
      rises in rectal temperature (from 36.6 degrees to 38.3 degrees C) or the ratings
      of perceived exertion in the two trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588680
TI  - Haematological and acute-phase responses associated with delayed-onset muscle
      soreness in humans.
AB  - Delayed-onset muscle soreness following unaccustomed or eccentric exercise is
      associated with inflammation, tissue necrosis and the release of muscle enzymes
      (Newham et al. 1983). We have investigated the time course of changes in
      circulating leucocytes and serum levels of some acute phase reactants, serum
      creatine kinase activity (CK) and muscle pain after a 40-min bout of bench
      stepping exercise in eight healthy untrained subjects. Leg muscle soreness was
      greatest 2 days after the exercise bout. Peak serum CK values [mean (SD) 540
      (502) IU.1-1] occurred 1-7 days post-exercise. Serum C-reactive protein (CRP) was
      unchanged from pre-exercise levels [7.8 (3.4) mg.1-1] immediately post-exercise
      [7.9 (2.3) mg.1-1] but rose to a peak of 17.0 (3.9) mg.1-1 1 day post-exercise,
      thereafter declining to basal levels. Serum levels of iron and zinc fell below
      pre-exercise levels for 1-3 days post-exercise. Serum albumin, IgG and IgM fell
      below pre-exercise levels from 1 day post-exercise, reaching minimal values
      (about 80% of basal levels) at 7 days post-exercise. The exercise did not appear
      to significantly affect serum levels of alpha-1-antitrypsin and alpha-1-acid
      glycoprotein. Two and three days after the exercise bout the circulating numbers
      of total leucocytes, neutrophils, monocytes and basophils fell 15-20% below pre
      exercise levels, whereas lymphocytes, eosinophils and platelets were unchanged.
      The results indicate that a rapid acute phase inflammatory response is initiated
      within 1 day of a bout of exercise that induces delayed-onset muscle soreness,
      and that any later tissue necrosis that may occur is not accompanied by further
      marked changes in acute-phase reactants such as CRP.

PMID- 7588681
TI  - Relationships between muscle carnitine, age and oxidative status.
AB  - Muscle carnitine levels were examined in 31 younger [mean (SD), 27 (5) years] and
      27 older [49 (8) years] men. Needle biopsies were obtained from the lateral
      gastrocnemius or vastus lateralis muscles and assayed for free and total
      carnitine concentrations via a 5,5'-Dithiobis-(2-nitrobenzoic acid) DTNB-linked
      spectrophotometric procedure. A subgroup of subjects (n = 28) were assessed for
      citrate synthase (CS) and succinate dehydrogenase (SDH) activity, and type I
      muscle fiber composition (% type I fibers). An additional sub-group of nine
      subjects was assessed for free and total serum carnitine levels. No mean (SEM)
      differences in free [21.6 (0.7) vs 20.3 (0.9) mumol.g dry weight-1] and total
      [26.4 (0.6) vs 26.1 (0.9) mumol.g dry weight-1) muscle carnitine levels were
      found between the younger and older subjects, respectively. Correlational data
      revealed no significant relationships between total muscle carnitine and CS (r = 
      0.36), SDH (r = -0.26), or % type I fibers (r = -0.16). In addition, there was a
      low non-significant relationship between serum and muscle total carnitine
      concentrations (r = -0.44). These findings suggest that muscle carnitine levels
      are similar between younger and older males, and there does not appear to be any
      relationship between muscle carnitine and markers of muscle oxidative potential
      (i.e., oxidative enzymes, % type I fiber). Since serum carnitine is often used as
      an indicator of body carnitine status, it is noteworthy that we found a low
      negative relationship between blood and muscle carnitine concentrations.

PMID- 7588682
TI  - Obligatory anaerobiosis resulting from oxygen uptake-to-blood flow ratio
      dispersion in skeletal muscle: a model.
AB  - We constructed a computer model whereby the dispersion of the oxygen uptake-to
      blood flow ratio (VO2/Q) in working muscle could be altered around its mean level
      during simulated exercise. The model incorporated standard values for the cardiac
      output and whole-body O2 uptake responses to incremental exercise in humans.
      Dispersion of the VO2/Q ratio was induced by distributing Q in a Gaussian fashion
      around its appropriate mean value with a standard deviation (sigma). By
      increasing sigma, more regions of the muscle became "anaerobic" as the
      corresponding local muscle venous blood O2 content fell to zero; these regions
      thus required proportionally greater rates of lactate production to sustain the
      required energy transfer. The model yielded a relatively high mixed-muscle venous
      partial pressure of O2, suggesting that the latter may not be a sufficient
      indicator of whether or not there may be diffusional limitation to muscle O2
      transfer during exercise or whether or not there may be anaerobic production of
      lactate in certain regions of exercising muscle.

PMID- 7588684
TI  - Influence of posture on middle cerebral artery mean flow velocity in humans.
AB  - We determined middle cerebral artery, common carotid artery and temporal
      superficial artery Doppler derived flow velocities in ten subjects for 10 min
      after change in posture. Maximal changes were observed after about 3 min. The 10
      degrees head-down tilt position increased blood velocities in the common carotid
      artery by 13% (SD 4)% (P < 0.001), in the middle cerebral artery by 6% (SD 3)% (P
      < 0.001) and in the superficial temporal artery by 70% (SD 26)% (P < 0.001). In
      the standing position, there was an 18% (SD 9)% (P < 0.001) decrease in the
      common carotid blood velocities, with 14% (SD 6)% (P < 0.001) and 53% (SD 23)% (P
      < 0.001) reductions in the middle cerebral and superficial temporal artery
      velocities, respectively. At 9 min after the changes in posture, velocities in
      the middle cerebral artery were at the value of supine rest, whereas the common
      carotid blood velocity was not completely restored and deviations in the temporal
      artery velocity persisted. The data would suggest that cerebral blood flow is
      regulated with some delay and that such regulation is partially reflected in the
      common artery blood flow, since changes in a branch of the external carotid
      artery flow velocity remained.

PMID- 7588685
TI  - Catecholamines, lymphocyte subsets, and cyclic adenosine monophosphate production
      in mononuclear cells and CD4+ cells in response to submaximal resistance
      exercise.
AB  - We examined the effect of 30 min of submaximal resistance exercise on free and
      sulphoconjugated plasma catecholamine concentrations determined by high
      performance (-pressure) liquid chromatography separation, the distribution of
      circulating lymphocytes quantified by flow cytometry, and isoproterenol induced
      cyclic adenosine monophosphate (cAMP) production in mononuclear cells (MNL) and
      CD4+ cells. Venous blood samples were taken before, immediately after and 45 min
      after exercise. Resistance exercise increased free plasma adrenaline (A) and
      noradrenaline (NA) concentrations, whereas sulphoconjugated catecholamine
      concentrations remained unchanged. Exercise induced leucocytosis and
      lymphocytosis was predominantly manifested by an increase in the number of total
      lymphocytes, monocytes, CD3+, CD8+ cells and CD3- CD16/CD56+ cells.
      Redistribution resulted in a decrease in the CD4+:CD8+ ratio. The total number
      and distribution of lymphocytes returned to baseline after 45-min rest. An
      exercise-induced increase in the number of CD3- CD16/CD56+ cells was
      significantly correlated with the increase in plasma NA (r = 0.66; P = 0.035),
      indicating a NA dependent process of redistribution. The cAMP-production in MNL
      was significantly elevated after resistance exercise, when cells were stimulated
      with 1 mumol.1(-1) isoproterenol [pre-exercise 16.5 (SD 3.3); postexercise 21.6
      (SD 9.8); 45 min postexercise 10.7 (SD 2.8)]. The cAMP production in CD4+ cells
      was not affected by exercise. Therefore, it is discussed whether redistribution
      is responsible for the exercise induced increase in cAMP production in MNL.

PMID- 7588686
TI  - Effects of an endurance training programme on the passive and noradrenaline
      activated compliances of rat aorta.
AB  - The effects of a 12-week endurance training programme (treadmill) upon the
      passive and the noradrenaline-activated properties of the aorta were studied in
      15 trained and 24 sedentary rats. Aortic compliance was studied by measuring the
      length-tension curves of rings of the descending aorta without (passive
      properties) and with noradrenaline (noradrenaline activated) in a bubbling Krebs
      bath kept at a temperature of 37 degrees. The training effect on aortic volume
      compliance was studied by transforming the tension-length curves into a cross
      sectional area-pressure curve according to Laplace's law. The noradrenaline
      responsiveness was studied by the dose-effect curve. The mechanical data were
      correlated with the results of a histomorphometric study which measured the
      aortic wall thickness and the percentages and amounts of elastic, connective and
      muscle components. Passive aortic compliance and volume compliance were higher in
      endurance-trained rats whose tunica media presented a lower percentage of
      collagen and a larger amount of elastic tissue. The dose-effect curve showed that
      the maximal aortic response to noradrenaline was stronger in trained rats but
      that the half maximal effective dose was not different. As a consequence, the
      length-tension curves of the noradrenaline fully activated aorta were similar in
      trained and sedentary rats except at the highest tensions where collagen is the
      main factor determining aortic stiffness. The increased noradrenaline response in
      trained rats was probably the result of the hypertrophy of the smooth muscle
      cells as maximal active strain (Newtons per square metre) was similar in trained
      and sedentary rats.

PMID- 7588687
TI  - Effects of prolonged exercise on the contractile properties of human quadriceps
      muscle.
AB  - The contractile properties of the quadriceps muscle were measured in seven
      healthy male subjects before, during and after prolonged cycling to exhaustion.
      Special efforts were made to obtain measurements immediately after exercise. The
      exercise intensity corresponded to about 75% of estimated maximal O2 uptake and
      time to exhaustion was mean 85 (SEM 9) min. At the end of the cycling heart rate
      and perceived exertion for the legs were 94% and 97% of maximal values,
      respectively. Maximal voluntary isometric force (MVC) had decreased after 5 min
      of exercise to a mean 91 (SEM 4)% of the pre-exercise value (P < 0.05) and
      decreased further to a mean 82 (SEM 6) and mean 66 (SEM 5)% after 40-min cycling
      and at exhaustion, respectively. A new finding was that during recovery reversal
      of MVC occurred in different phases where the half recovery time of the initial
      rapid phase was about 2 min. The MVC was a mean 80 (SEM 2)% of the pre-exercise
      value after 30 min and was not affected by superimposed electrical stimulation.
      Maximal voluntary concentric and eccentric forces decreased to 74% and 80% of
      initial values at exhaustion (P < 0.05). The kinetics of isometric contraction
      expressed as the time between 5% and 50% of tension (rise time) and the time
      between 95% and 50% of tension (relaxation time) were not significantly affected
      by the prolonged cycling. The electromechanical delay measured as the time
      between the first electrical stimulus and 5% of tension decreased from a mean 32
      (SEM 1) ms at rest to a mean 26.6 (SEM 0.6) ms at fatigue (P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7588688
TI  - Effects of 6 versus 12 days of heat acclimation on heat tolerance in lightly
      exercising men wearing protective clothing.
AB  - This study investigated the influence of 6 versus 12 days of heat acclimation on
      the tolerance of low-intensity exercise in the heat while wearing protective
      clothing. Sixteen young men were acclimated by treadmill walking (50% of each
      subject's maximal aerobic power for 60 min.day-1) in a climatic chamber [40
      degrees C dry bulb (db), 30% relative humidity] for either 6 consecutive days or
      two 6-day periods, separated by a 1-day rest. Before and after heat acclimation,
      the subjects performed a heat-exercise test (1.34 m.s-1, 0% grade; 40 degrees C
      db, 30% relative humidity), either under control conditions [wearing normal light
      combat clothing (continuous exercise; n = 5)] or when wearing protective clothing
      resistant against nuclear, biological, and chemical (NBC) agents (repeated bouts
      of 15-min walk + 15-min rest; n = 8). Criteria for halting the test exercise were
      a rectal temperature (Tre) of 39.3 degrees C, a heart rate (fc) > or = 95% of the
      subject's observed maximum, unwillingness of the subject to continue, or the
      elapse of 150 min. Heat acclimation decreased overall test values of Tre, fc, and
      mean skin temperature for both control and protective clothing conditions. When
      wearing normal combat clothing, acclimation responses were about twice as large
      after 12 than after 6 days, but the response was not increased by longer
      acclimation when wearing NBC protective clothing. Both 6 and 12 days of
      acclimation increased tolerance times in NBC protective clothing by about 15 min
      [from 97 (4) to 112 (6) min and from 108 (10) to 120 (10) min for 6 and 12 days,
      respectively]. We conclude that the physiological strain and limitation of heat
      exercise tolerance imposed by wearing NBC protective clothing are not reduced if
      heat acclimation is prolonged from 6 to 12 days.

PMID- 7588689
TI  - Determination of body heat storage in clothing: calorimetry versus thermometry.
AB  - Two methods of estimating body heat storage were compared under differing
      conditions of clothing, training, and acclimation to heat. Six male subjects
      underwent 8 weeks of physical training [60-80% of maximal aerobic power (VO2max)
      for 30-45 min.day-1, 3-4 days.week-1 at < 25 degrees C dry bulb (db)] followed by
      6 consecutive days of heat acclimation (45-55% VO2max for 60 min.day-1 at 40
      degrees C db, 30% relative humidity)]. Nine other male subjects underwent
      corresponding periods of control observation followed by heat acclimation. Before
      and after each treatment, subjects walked continuously on a treadmill (1.34 m.s
      1, 2% grade) in a climatic chamber (40 degrees C db, 30% relative humidity) for
      an average of 118 min (range 92-120 min) when wearing normal light combat
      clothing and for an average of 50 min (range 32-68 min) when wearing protective
      clothing resistant to nuclear, biological, and chemical agents. The heat storage
      was determined calorimetrically (by the balance of heat gains and losses) and
      thermometrically [by the conventional equations, using one or two set(s) of
      relative weightings for the rectal temperature (Tre) to mean skin temperature
      (Tsk) of 4:1 and 4:1, 2:1 and 4:1, or 2:1 and 9:1 in thermoneutral and hot
      environments, respectively]. Tsk was calculated from 12-site measurements,
      weighted according to the regional distribution of body surface area and the
      first eigenvectors of principal component analysis. There were only minor
      differences (< 5%) between the heat storage values calculated by given weighting
      factors for Tre and Tsk, whether the individual coefficients were derived from
      estimates of regional surface area or principal component methodologies. When
      wearing normal clothing, no significant differences were found between the two
      estimates of heat storage (calorimetry vs thermometry with an invariant relative
      weighting of 4:1) in any experimental condition, with one specific exception:
      when wearing protective clothing, thermometry underestimated the heat storage by
      24-31%. This under-estimation was attenuated by using two sets of relative
      weightings of 2:1 and 4:1 or 2:1 and 9:1. The results suggest that when subjects
      wearing protective clothing are transferred from thermoneutral to hot
      environments, the accuracy of thermometric estimates of heat storage can be
      improved by using two sets of weighting factors for Tre and Tsk.

PMID- 7588690
TI  - Kinetics of plasma potassium concentrations during exhausting exercise in trained
      and untrained men.
AB  - The purpose of this study was to examine the time course of changes in plasma
      potassium concentration during high intensity exercise and recovery in trained
      and untrained men. The subjects performed two exercise protocols, an incremental
      test and a sprint, on a cycle ergometer. A polyethylene catheter was inserted
      into the antecubital vein to obtain blood samples for the analysis of plasma
      electrolyte concentrations and acid-base parameters, during and after exercise.
      During both tests, venous plasma sodium, potassium and chloride concentrations
      increased in all the subjects, although the largest relative increase was
      detected in potassium concentration--35% and 31% over rest in the progressive
      test and 61% and 37.7% in the sprint test, for cyclists and controls,
      respectively. After exercise plasma potassium concentration decreased
      exponentially to below resting values. There was a linear correlation between the
      amount of potassium accumulated in plasma during exercise and the amount
      eliminated from plasma when the exercise ceased. We found that, although plasma
      potassium accumulation occurred in both forms of exercise in the trained and
      nontrained subjects, the time constant of potassium decrease following exercise
      was shorter in the trained subjects. Thus, the trained subjects exhibited a
      better capacity to recover to resting concentrations of plasma potassium. We
      propose that the extracellular potassium accumulation acts as a negative feedback
      signal for sarcolemma excitability depending on the muscle metabolic rate.

PMID- 7588692
TI  - Maximal physical work performance with European standard based fire-protective
      clothing system and equipment in relation to individual characteristics.
AB  - Every fire fighter needs to wear fire-protective clothing and a self-contained
      breathing apparatus (SCBA) several times a year while carrying out various fire
      fighting and rescue operations in hazardous work environments. The aim of the
      present study was to quantify the effects of a multilayer turnout suit designed
      to fulfil European standard EN 469 used over standardized (Nordic) clothing and
      with SCBA (total mass 25.9 kg) on maximal physical work performance, and to
      evaluate the relationship between individual characteristics and power output
      with the fire-protective clothing system and SCBA. The subjects were 12 healthy
      firemen aged 26-46 years. The range of their body mass, body fat and maximal
      oxygen consumption was 69-101 kg, 10-20% and 2.70-5.86 l.min-1, respectively. The
      maximal tests without (control) and with the fire-protective clothing system and
      SCBA were carried out on a treadmill in a thermoneutral environment. When
      compared to the control test, the decrease in the maximal power output in terms
      of maximal working time and walking speed averaged 25% (P < 0.001) varying from
      18% to 34% with the fire-protective clothing system and SCBA. At maximum, no
      significant differences were found in pulmonary ventilation, absolute oxygen
      consumption, the respiratory exchange ratio, heart rate, systolic blood pressure,
      the rate-pressure product, mechanical efficiency, and the rating of perceived
      exertion between the tests with and without the fire-protective clothing system
      and SCBA. The reduction of the power output was related to the extra mass of the
      fire protective clothing and SCBA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588691
TI  - Phonomyogram from single motor units during voluntary isometric contraction.
AB  - The purpose of this study was to determine the characteristics of the specific
      phonomyogram (PMG) of active motor units activated during voluntary isometric
      contractions. The electromyogram (EMG) and PMG were recorded from 87 anconeus
      motor units in 14 subjects. The elementary PMG from single motor units was
      analysed with a spike-triggered averaging technique. The electro-acoustical delay
      was 3.5 (SD 1.1) ms, which is within the range of values reported in the
      literature for PMG evoked by motor nerve stimulation. All motor units
      demonstrated a pattern of impulsive sounds with a duration of 87.2 (SD 10.7) ms.
      These results would imply that PMG is linked to the contractile activity of the
      motor units. These results also would suggest that PMG recorded from a
      contracting muscle in situ reflects the summation of elementary PMG during
      voluntary contraction more than the overall mechanical properties of the muscle.

PMID- 7588693
TI  - Anaerobic and aerobic peak power output and the force-velocity relationship in
      endurance-trained athletes: effects of aging.
AB  - The aim of this investigation was to test the hypothesis that the anaerobic peak
      power output (Pan, peak) declines more than the peak aerobic power (Paer, peak)
      with increasing age. In addition, the force-velocity (F-v) relationship was
      studied to determine which of these two factors is primarily responsible for the
      expected alterations in anaerobic power. The Pan, peak, the maximal F when v is
      equal to zero (F0) and the maximal v when F is equal to zero (v0) were assessed
      by F-v test i.e. a brief intense intermittent exercise test using incremental
      braking forces. The Paer, peak was measured by a maximal increment exercise test.
      A group of 12 young athletes (YA) and 12 master athletes (MA) mean age 24.8 (SEM
      1.3) and 65.1 (SEM 1.2) years, respectively, participated in this study. The YA
      and MA had similar body masses, heights and endurance training schedules. The
      results showed that Pan, peak was 42.7% lower in the older subjects,
      corresponding to mean values of 1089 (SEM 40) compared to 624 (SEM 33) W (t =
      8.9, P < 0.001) for YA compared to MA, respectively. The F0 and V0 indices showed
      values that were lower by 30.3% and 15.2%, respectively. The Paer, peak was 35%
      lower with mean values of 323 (SEM 12) W for YA compared to 210 (SEM 6) W for MA
      (t = 8.3, P < 0.001). The mean maximal oxygen uptake was 34.7% lower with 4240
      (SEM 160) ml.min-1 for YA compared to 2770 (SEM 120) ml.min-1 for MA (t = 7.2, P
      < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588694
TI  - Effect of aerobic capacity on sweat rate and fluid intake during outdoor exercise
      in the heat.
AB  - We measured the aerobic capacity, sweat rate and fluid intake of trained athletes
      during outdoor exercise and examined the relationship between aerobic capacity
      and thermoregulatory responses at high ambient temperatures. The maximal aerobic
      capacity (VO2max) of the subjects, nine male baseball players of college age, was
      determined by maximal exercise tests on a cycle ergometer. The subjects practised
      baseball regularly without drinking fluids from 1330 to 1530 hours. After 30 min
      rest, they played a baseball game with free access to a sports drink at 15
      degrees C from 1600 to 1830 hours. At a mean ambient temperature of 36.7 (SEM
      0.2) degree C, the mean percentage of body mass loss (delta mb) and increase of
      oral temperature (delta To) from 1330 to 1530 hours was 3.47 (SEM 0.12)% and 0.81
      (SEM 0.14) degree C, respectively. The sweat loss from 1330 to 1830 hours was
      56.53 (SEM 1.56)ml.kg-1 of body mass (mb) while the mean fluid consumption was
      44.78 (SEM 2.39)ml.kg-1 of mb, with recovery of 76.08 (SEM 2.81)% of sweat loss.
      The VO2max was significantly inversely correlated with delta mb, fluid intake and
      rehydration amount, but showed no correlation with delta To. These results would
      suggest that at a given exercise intensity in subjects with a higher aerobic
      capacity body temperature is maintained with a lower sweating rate than that in
      subjects with a lower aerobic capacity.

PMID- 7588697
TI  - Hyperoxia during recovery from consecutive anaerobic exercises in the sickle cell
      trait.
AB  - The sickle cell trait (HbAS) does not affect anaerobic exercise performance.
      However, lower blood lactate concentrations ([La-]) are consistently found during
      repeated anaerobic exercise in HbAS, and could be related to type of recovery. To
      study this, on three different occasions 17 HbAS and 17 matched control athletes
      (HbAA) underwent a series of three maximal cycle exercise tests of approximately
      2-min duration, separated by 10-min recovery periods of rest, breathing either
      room air (P) or 100% oxygen (H), or of light pedaling (A). In all tests, work
      performed, heart rate, blood hematocrit, and [La-] were measured. Despite similar
      evolution of performance in each series of three anaerobic exercises,
      significantly lower [La-] were consistently found in HbAS in P and A, compared to
      HbAA (P < 0.0001). However, in H, similar [La-] was found in HbAS and HbAA.
      Higher mean heart rates were consistently measured in HbAS at exhaustion, and
      during the first 4 min of recovery, these differences being unrelated to type of
      recovery. We conclude that type of recovery does not influence subsequent
      performance in HbAS or HbAA. We speculate that improved regional oxygen
      availability in exercising muscle is associated with marked modification of
      lactate kinetics in highly trained HbAS, but not in similarly fit HbAA athletes.

PMID- 7588701
TI  - The effect of diurnal variation on the regional differences in sweating and skin
      blood flow during exercise.
AB  - The aim of the present study was to examine changes in the control of heat
      dissipation responses to exercise associated with the diurnal variation in core
      temperature from the viewpoint of the regional response patterns. We studied
      seven men during exercise on a cycle ergometer at 100 W for 40 min at 25 degrees
      C at 0630 (morning) 1630 (evening) hours on 2 separate days. Oesophageal
      temperature (T(oes)), local skin temperature, local sweating rate (msw) on the
      forehead, back, forearm and thigh, and skin blood flow by laser Doppler flowmeter
      (LDF) on the back and forearm were measured continuously. The T(oes) at rest was
      significantly higher in the evening than in the morning, the difference averaging
      approximately 0.4 degrees C (P < 0.05). The T(oes) thresholds for each site in
      msw and that for back in LDF were significantly different between the two times
      of day (P < 0.05). The change in T(oes) thresholds for sweating and
      vasodilatation for morning and evening were similar to T(oes) at rest. Although
      msw on the forehead was significantly higher in the morning than in the evening,
      msw on the back was significantly higher in the evening than in the morning (P <
      0.05). Total local sweating rate (msw,tot) for each site during exercise was
      significantly higher on the forehead than on the forearm in the morning, and on
      the back than on the forearm in the evening, respectively (P < 0.05). The results
      would suggest that the diurnal variation of heat-dissipation responses to
      exercise is influenced not only by a central controlling mechanism but also by
      changes in the regional differences.

PMID- 7588699
TI  - Effects of moisture absorption by clothing on thermal responses during
      intermittent exercise at 24 degrees C.
AB  - The effects of two kinds of clothing with different properties with respect to
      moisture absorption on thermophysiological responses and pulse rate were studied
      during intermittent exercise at an ambient temperature (Ta) of 24 degrees C. The
      two kinds of clothing ensemble tested were cotton T-shirt with short sleeves and
      cotton long-sleeved working dress with full-length trousers (C), and polyester T
      shirt with short sleeves and polyester long-sleeved working dress with full
      length trousers (P), the thermal resistances of which were nearly equal. Five
      women aged 21-32 years, served as subjects. The environmental conditions were 24
      degrees C Ta, 50% relative humidity and 0.14 m.s-1 air velocity. The subjects,
      wearing either C or P, exercised for 10-min on a cycle ergometer at an intensity
      of 30% maximal oxygen uptake and then 10-min rest. This sequence was repeated
      four times. Rectal and skin temperatures at several sites, local sweating rate,
      pulse rate and clothing microclimates were continuously compared between C and P
      throughout the experiment. The major findings were firstly, rectal temperature
      rose significantly higher in P; secondly, pulse rate was higher in P both during
      exercise and rest; thirdly, clothing surface temperature on the back rose highly
      significantly during the fourth exercise period and then fell significantly
      during the fourth rest period in C; and fourthly, four out of five subjects felt
      wetter in P during the latter half of the experiment. These results are discussed
      from the viewpoint that the reduced thermal insulation due to the absorption of
      moisture in C accelerated dry heat loss, resulting in an inhibition of the
      increases in core temperature and pulse rate.

PMID- 7588696
TI  - Exercise-induced changes in the expression of surface adhesion molecules on
      circulating granulocytes and lymphocytes subpopulations.
AB  - This study examined the relationship between exercise-induced changes in the
      concentration of circulating immunocompetent cells and their surface expression
      of adhesion molecules: L-selectin (CD62L) and three beta 2-integrins [LFA
      1(CD11a/CD18), Mac-1 (CD11b/CD18), and p150/95(CD11c/CD18)]. Eight young male
      volunteers exercised on a cycle ergometer for 60 min at 60% maximal oxygen
      uptake. Peripheral blood samples, collected every 30 min throughout exercise and
      during the 2-h recovery period, were used for flow-cytometric analysis. The
      experimental results were compared with control data obtained ever 60 min at
      corresponding times of the nonexercise day. The exercise regimen induced a
      granulocytosis and a lymphocytosis, mainly due to an elevation of CD8+ and CD16+
      cells. During recovery, a further granulocytosis occurred but accompanied by a
      lymphopenia. The increased CD8+ cell-count during exercise was characterized by a
      selective mobilization of the CD62L- and CD11ahigh cells, i.e. primed CD8+ cells.
      A postexercise suppression of CD4+ cell-count was derived only from CD62L+ cells.
      The CD11b+ and CD11c+ lymphocytes also increased during exercise, largely
      attributable to an increase in CD16+ cells which co-expressed CD11b and CD11c
      molecules. The CD62L surface density of granulocytes increased significantly
      during recovery. This resulted from a selective influx of CD62Lhigh granulocytes
      into the circulation. There were no significant changes in per-cell density of
      the three beta 2-integrins on granulocytes and lymphocytes throughout the
      experimental period. These results suggest that the cell-surface expression of
      CD62L (and CD11a) molecules is associated with the differential mobilization of
      CD8+ cells during exercise, the postexercise suppression of CD4+ cell-counts and
      the granulocytosis following exercise.

PMID- 7588695
TI  - Effectiveness of lower-level voluntary exercise in disease prevention of mature
      rats. I. Cardiovascular risk factor modification.
AB  - To evaluate the chronic effects of voluntary exercise at lower levels on primary
      cardiovascular risk factors, inactive strain male Fischer rats were housed either
      with or without free access to activity wheels under controlled environmental
      conditions. The average amount of exercise for the 35-week duration was 722 (SD
      362) m.day-1.rat-1, which was among the lowest found in the existing reports.
      Nonetheless, the body mass gains of the exercising rats were markedly inhibited,
      being 13% less (P < 0.001) than those of the sedentary controls, despite a 22%
      increase in food consumption (P < 0.0001), suggesting a remarkable prevention of
      adiposity. A noticeable improvement of serum lipid profiles was also found; a 53%
      reduction in triglyceride concentrations (P < 0.01) and a 13% increase in high
      density lipoprotein cholesterol concentrations (P < 0.05). In addition, resting
      systolic blood pressure was lowered by 7% (P < 0.01). These results would suggest
      that even lower-level physical activity, if continued regularly, will attenuate
      the age-related development of cardiovascular risk factors associated with a
      sedentary lifestyle.

PMID- 7588703
TI  - Critical power test for ramp exercise.

PMID- 7588698
TI  - A new instrument for the measurement of rib cage and abdomen circumference
      variation in respiration at rest and during exercise.
AB  - A simple and inexpensive new extensometer for measuring changes in chest wall
      circumference during human respiratory movements is presented. The instrument
      detects the delay between ultrasound emission and reception at opposite ends of
      two rubber tubes encircling the rib cage and abdomen. Assuming a two degree of
      freedom model of the chest wall and employing an isovolume procedure for
      determination of volume-motion coefficients, extensometer estimation of tidal
      volume (VT) from changes of rib cage and abdomen circumference was compared with
      spirometer measurements at rest and during exercise on a cycle ergometer (55-155
      W) in six subjects and, in four of them, on a treadmill (4-12 km.h-1). In three
      subjects hypercapnic hyperpnoea at rest was also studied. The slopes of the
      linear relationship between extensometer and spirometer VT (litres) averaged
      0.9967 (SD 0.0117) (r2 = 0.995-0.998; n = 90-143) for cycle ergometer exercise,
      1.0072 (SD 0.0078) (r2 = 0.991-0.998; n = 75-93) for treadmill exercise and
      0.9942 (SD 0.0188) (r2 = 0.997-0.998; n = 18-25) for hypercapnic hyperpnoea. In
      all instances the slope of the regression line was consistent with the model of
      the identity line (slope = 1). The changes in end-expiratory lung volume between
      respiration at rest and during exercise were determined by the extensometers, and
      were nearly identical (98.4% on average) to those measured with the spirometer
      (r2 = 0.945; n = 24). It is concluded that determination of chest wall
      circumference with this new instrument is suitable for quantitative measurement
      of ventilation and lung volume variations in humans under most physiological
      conditions.

PMID- 7588702
TI  - Increased phagocytic capacity of the blood, but decreased phagocytic activity per
      individual circulating neutrophil after an ultradistance run.
AB  - The effect of a long strenuous endurance exercise on the phagocytic function of
      neutrophils was examined. 9 athletes [7 males, 2 females, age: 36-68 years, body
      mass: 64 (SD 10) kg, height: 175 (SD 10) cm] completed a competetive 100 km run
      in 8:07 (median value; range: 7:29-9:50 hours). In a whole blood assay the
      phagocytosis of opsonized E. coli, the receptor density of the Fc gamma receptor
      3 (CD16) and the complement receptor 3 (CD11b, direct immunofluorescence) of
      neutrophils were measured on a per cell basis by flow cytometry before and up to
      3 hours after the race. The phagocytic rate (percentage of neutrophils
      incorporating bacteria) was unchanged after exercise, whereas the phagocytic
      activity (number of incorporated bacteria per cell) was significantly reduced by 
      34 (SD 8) % (Wilcoxon test, P < 0.001). The total phagocytic capacity of the
      blood increased 2-3fold post exercise. The surface antigen expressions of CD11b
      and CD16 were unaffected by the ultradistance run. The results indicate either a
      reduced phagocytic function of neutrophils on a single cell basis or the
      mobilization of neutrophils of the marginal pool with a lower phagocytic
      activity. However, after a long endurance exercise the phagocytotic capacity of
      the blood was enhanced due to increased cell concentrations.

PMID- 7588700
TI  - Effect of prior isometric muscle action on concentric torque output during
      plantar flexion.
AB  - The influence of different levels of prior isometric muscle action on the
      concentric torque output during plantar flexion was examined at two angular
      velocities (60 degrees.s-1 and 120 degrees.s-1) in ten healthy female subjects.
      The levels of the prior muscle actions were 25%, 50%, 75% and 100% of the maximal
      voluntary isometric contraction (MVIC). A KINetic-COMmunicator II dynamometer was
      used to measure torque output during plantar flexion within a range of motion of
      78 degrees-120 degrees of the ankle joint. Simultaneous recordings of
      electromyograms (low-pass filtered and rectified) were obtained from the
      gastrocnemius medialis muscle and the soleus muscle. Torque-angle curves were
      made for the plantar flexions using different prior muscle actions. Up to 75% of
      MVIC, the torque output in the first part of the range of motion increased with
      the level of the prior isometric muscle action; at higher levels of MVIC the
      torque did not appear to increase any further. Later in the range of motion,
      after 24 degrees in the plantar flexion at a velocity of 60 degrees.s-1 and 31
      degrees at 120 degrees.s-1, the prior muscle actions had no further influence. No
      increase was found in the electromyograms, with one exception, during the
      concentric movements when preceded by higher levels of MVIC. It would seem
      therefore that the increase in torque output early in the range of motion cannot
      be explained on the basis of differences in electrical muscle activation in this
      study.

PMID- 7588704
TI  - Gender differences in physiological reactions to thermal stress.
AB  - Following an extensive anthropometric evaluation, thermoregulatory responses were
      studied in nine men and nine women who performed immersed exercise with post
      exercise rest in 28 degrees C water. During the post-exercise period esophageal
      temperature (Tes), oxygen consumption, heat flux and skin blood perfusion were
      monitored at 10 s intervals, with average minute values used for calculations.
      The delta Tes (relative to resting Tes) at which sweating abated and shivering
      commenced were defined as the delta Tes thresholds for the cessation of sweating
      and onset of shivering, respectively. No significant gender differences were
      evident in the sweating and shivering threshold delta Tes values, or the
      magnitude of the null-zone. Using z-tests for parallelism the rates of core
      cooling across the null-zone were not found to differ significantly between
      genders, nor were the slopes of the perfusion: delta Tes responses across the
      null-zone or the post-threshold shivering responses (ml.kg-1.min-1.degrees C-1).
      The slope of the sweating response (measured from immersion until sweat
      cessation; g.m-2.min-1 degree C-1) was, however, significantly lower in the
      female than in the male samples (z = 3.93; P < 0.01). Despite the gender-related
      dimorphic distribution of adipose tissue, both men and women lost equal
      proportions of their total heat flux from central and peripheral measurement
      sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588705
TI  - Two regions with differential growth-modulating activity in the N-terminal domain
      of ras GTPase-activating protein (p120GAP) src homology and Gly-Ala-Pro-rich
      regions.
AB  - Ras GTPase-activating protein of 120 kDa (p120GAP) consists of a hydrophobic Gly
      Ala-Pro-rich stretch and src homology 2 and 3 (SH2/SH3) domains in the N-terminal
      half, and a Ras GTPase-activating domain at the C-terminus. In order to evaluate
      the potential for cell-growth regulation of the N-terminal region of p120GAP, we
      isolated three distinct clones of rat 3Y1 fibroblast that express either the
      SH2/SH3 regions alone, the N-terminal half, or the whole p120GAP. Clones that
      express the SH2-SH3-SH2 regions of 37 kDa (p37SH2/3) at a level of only 15-30%
      that of endogenous p120GAP, but not clones expressing complete p120GAP or its N
      terminal half of 55 kDa (p55GAP-N), showed significant growth-enhancing
      properties, including a higher saturation density and increased uptake of 2
      deoxyglucose. Clones expressing p37SH2/3 or p55GAP-N maintained high levels of
      tyrosine-phosphorylated p190 and p62, both of which bind the SH2 domain of
      p120GAP, while clones expressing the whole p120GAP showed no tyrosine
      phosphorylation of p62. Furthermore, in the presence of a phorbol ester, only the
      clones expressing p37SH2/3 showed increased tyrosine phosphorylation of p62 and c
      fos expression. These clones also showed the ability of colony formation in soft
      agar. These results indicate that the N-terminal domain of p120GAP consists of
      two regions with differential growth-enhancing activities and suggest that the
      transforming potential of SH2/SH3 regions is blocked by the N-terminal
      hydrophobic Gly-Ala-Pro stretch.

PMID- 7588707
TI  - Redox-shift of the pheromone-binding protein in the silkmoth Antheraea
      polyphemus.
AB  - In pheromone-sensitive hairs of the male silkmoth Antheraea polyphemus, two
      electrophoretically distinct pheromone-binding proteins (PBPs) are present. They
      indicate no amino acid sequence diversity according to peptide mapping, but
      differ in their redox state, as shown by free-sulfhydryl-group-specific cleavage
      at cysteine residues with 2-nitro-5-thiocyanobenzoic acid. In kinetic studies,
      the pheromone was initially bound mainly by the reduced PBP but later by the
      oxidized PBP, where all six cysteine residues form disulfide bonds. This redox
      shift was observed only in the homogenate of isolated olfactory hairs, where
      proteins of the sensillum lymph and receptive dendrites are present. In control
      experiments with purified binding proteins, the proportion of pheromone bound to
      the oxidized PBP did not increase with increasing incubation time, suggesting
      that disulfide formation does not occur spontaneously but is mediated by the
      sensory hairs, possibly by interaction with the receptor cell membrane. These
      data suggest that arriving hydrophobic pheromone molecules are first bound by the
      reduced PBP and transported through the aqueous sensillum lymph towards the
      receptor molecules of the dendritic membrane. The oxidized complex might not be
      able to activate further receptors and, thus, effectively deactivate the
      pheromone molecules within the sensillum lymph.

PMID- 7588706
TI  - A single point mutation in the splice donor site of the low-density-lipoprotein
      receptor gene produces intron read-through, exon-skipped and cryptic-site
      utilized transcripts.
AB  - Familial hypercholesterolemia is a genetic disorder caused by mutations of the
      low-density-lipoprotein (LDL) receptor gene. We characterized the structures of
      LDL receptor mRNA transcripts in the fibroblasts of a homozygous patient carrying
      a single base substitution (T-->C) at the 5' splice donor site of intron 12 of
      the LDL receptor gene. We identified three aberrant transcripts as a consequence
      of intron-12 read-through, exon-12 skipping and utilization of a cryptic splice
      donor site. Only a point mutation at the 5' splice donor site caused the
      production of three alternatively spliced products. None of these transcripts
      produced a functional LDL receptor protein in this patient.

PMID- 7588708
TI  - Protein phosphatase 2B of Saccharomyces cerevisiae is required for tolerance to
      manganese, in blocking the entry of ions into the cells.
AB  - The role of protein phosphatase 2B (PP2B/calcineurin) of Saccharomyces cerevisiae
      in the tolerance to divalent cations was investigated. PP2B-deficient mutants
      were found to be sensitive to MnCl2, but not to ZnCl2, CuCl2, NiCl2 and CoCl2. By
      measuring both manganese uptake and its efflux, it was found that the sensitivity
      of the mutant cells was due to an increase in manganese uptake and that the wild
      type cells were able to prevent manganese entry into the cells, rather than
      export it in a more efficient manner. In the presence of the immunosuppressant
      FK506, the behavior of wild-type cells became similar to that of PP2B mutants.
      Out of various divalent cations tested, externally added magnesium ions were able
      to block manganese uptake in both wild-type and PP2B mutant strains.

PMID- 7588709
TI  - Construction of stable BHK-21 cells coexpressing human secretory glycoproteins
      and human Gal(beta 1-4)GlcNAc-R alpha 2,6-sialyltransferase alpha 2,6-linked
      NeuAc is preferentially attached to the Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1
      3)-branch of diantennary oligosaccharides from secreted recombinant beta-trace
      protein.
AB  - The human beta-trace protein has been cloned and has been expressed for the first
      time in a mammalian host cell line. Stable BHK-21 cell lines exhibiting altered
      terminal sialylation properties were constructed by cotransfection of cells with
      the plasmids pMT-beta TP or pAB3-1 which contain the cDNAs encoding the human
      secretory glycoproteins beta-trace protein or antithrombin III and pABSial
      containing the human Golgi enzyme CMP-NeuAc:Gal(beta 1-4)GlcNAc-R alpha 2,6
      sialyltransferase (ST6N) gene. The beta-trace protein was purified by
      immunoaffinity chromatography and N-linked oligosaccharides were subjected to
      carbohydrate structural analysis. The enzymically liberated oligosaccharides were
      found to consist of 90% of diantennary chains as is the case for natural beta
      trace protein from human cerebrospinal fluid. About 90% of the total
      oligosaccharides were recovered in the monosialo and disialo fractions in a ratio
      of 1:5. The monosialylated oligosaccharides of beta-trace protein coexpressed
      with human ST6N were found to contain NeuAc in alpha 2,6- or alpha 2,3-linkage in
      the same ratio. From 1H-NMR analysis as well as calculations of peak areas
      obtained by HPLC, 60% of the molecules of the disialo fraction were found to
      contain NeuAc in both alpha 2,3- and alpha 2,6-linkage to Gal beta(1-4)GlcNAc-R,
      whereas 40% of the molecules of this fraction contained NeuAc in only alpha 2,3
      linkage to Gal(beta 1-4)GlcNAc-R. The alpha 2,6-linked NeuAc was shown to be
      attached preferentially to the Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3) branch
      of the diantennary structure. Therefore the in vivo specificity of the newly
      introduced recombinant human ST6N observed in this study supports the previously
      reported in vitro branch specificity of the bovine colostrum ST6N activity.
      Furthermore, these studies demonstrate the suitability of genetically engineered
      mammalian host cell lines with novel glycosylation properties for the production
      of human-type glycosylated secretory recombinant polypeptides.

PMID- 7588710
TI  - Comparative study on the conformation of phalloidin, viroisin, and related
      derivatives in aqueous solution.
AB  - We investigated the conformations of toxic phalloidin and viroisin in aqueous
      solution using 500-MHz 1H-NMR spectroscopy in conjunction with molecular
      modeling. The conformations of two non-toxic phalloidin derivatives,
      secophalloidin and dethiophalloidin, were also correspondingly studied for
      comparison purposes. Results indicate that the non-toxic peptides have a multiple
      conformation, whereas the toxic peptides are comprised of a rigid molecule. It
      was found that the conformation of phalloidin partially resembles that of
      viroisin in the region of Cys3-Pro4-Ala5-Trp6, being different from that of the
      non-toxic peptides; thereby suggesting this region plays an important role
      leading to their toxicity.

PMID- 7588711
TI  - Resolution of the nirD locus for heme d1 synthesis of cytochrome cd1 (respiratory
      nitrite reductase) from Pseudomonas stutzeri.
AB  - The genetic organization of the nirD locus of Pseudomonas stutzeri ZoBell,
      necessary for a catalytically active cytochrome cd1 (EC 1.9.3.2), was determined.
      The locus comprises the unidirectionally transcribed open reading frames
      nirFDLGH, downstream of nirMC of the nir gene cluster, and immediately upstream
      of the norCB operon encoding nitric oxide (NO) reductase (EC 1.7.99.7). Notable
      sequence relatedness was found between NirF and cytochrome cd1 (NirS), within
      NirDLGH, and between NirM and NirC, suggesting several gene duplication events in
      this region. The derived NirF protein (391 amino acids, M(r) 43,137) has 23.8%
      identity (51.1% overall similarity) with NirS, but lacks the N-terminal heme-c
      binding domain of NirS. Insertional mutagenesis of the five open reading frames
      resulted in the loss of respiratory nitrite reductase activity in vivo and in
      vitro. Mutant strains, when induced with nitrate for denitrification, synthesized
      a periplasmic cytochrome cd1 lacking heme d1. The defect was caused by the
      inability of the cell to synthesize heme d1. The nirD locus is proposed to encode
      a multimeric and multifunctional enzyme complex involved in the synthesis of heme
      d1. Mutations in nirFDLGH lowered substantially the expression level of norCB.
      Nir- mutants, unable to generate NO in vivo, provide indirect evidence for an NO
      sensor and an inducer role of NO for its cognate reductase.

PMID- 7588713
TI  - Protein disulphide isomerase and a lumenal cyclophilin-type peptidyl prolyl cis
      trans isomerase are in transient contact with secretory proteins during late
      stages of translocation.
AB  - The transport of a presecretory protein into the mammalian endoplasmic reticulum
      can be divided into early translocation events which include specific targeting
      of the presecretory protein to and insertion into the endoplasmic reticulum
      membrane and late translocation events, comprising signal sequence cleavage,
      completion of translocation and folding of the secretory protein into a
      functional conformation. The microsomal membrane proteins Sec61 alpha p and
      translocating-chain-associating membrane protein were previously identified as
      being in close contact with a nascent presecretory protein at an early step of
      translocation. Here, we investigated whether additional microsomal proteins are
      in contact with translocating chains during or immediately after transit. This
      was addressed by crosslinking after release of the nascent chain from Sec61 alpha
      p. We observed two additional membrane proteins interacting with the nascent
      precursor in the early stages of translocation and three lumenal proteins
      interacting with the processed polypeptide chain in the late stages of
      translocation. One of the lumenal proteins was identified as protein disulphide
      isomerase by immunoprecipitation. Another of the lumenal proteins was suggested
      to be a lumenal cyclophilin-type peptidyl prolyl cis-trans isomerase by the
      effect of cyclosporin A. We propose that molecular chaperones, such as protein
      disulphide isomerase and cyclophilin may represent two of the lumenal proteins
      which are involved in completion of translocation.

PMID- 7588712
TI  - Insulin-induced proteolysis of the insulin receptor alpha-subunit from rat liver
      does not occur in vivo but is prevented in vitro by blood serum proteinase
      inhibitors.
AB  - Insulin binding to rat liver plasma membranes promotes the action of a plasma
      membrane proteinase that degrades the 135-kDa alpha-subunit of the insulin
      receptor to a 120kDa product. It has been proposed that this proteolysis may be
      the initial step leading to down-regulation of the hepatic insulin receptor
      [Lipson, K. E., Kolhatkar, A. A. & Donner, D. B. (1988) J. Biol. Chem. 263, 10495
      10501]. Our results confirm that liver plasma membrane fractions from intact or
      perfused rat liver and from isolated rat hepatocytes do have a proteinase that
      degrades the alpha-subunit of the insulin receptor, whose activity increases
      significantly in the presence of insulin. In contrast to these in vitro results,
      plasma membranes and Golgi fractions isolated from liver at different times after
      a single intravenous injection of insulin to rats only contained intact alpha
      subunits of the insulin receptor. Insulin administration was associated with a
      rapid and reversible translocation of insulin receptors from the plasma membranes
      to Golgi fractions but did not affect their total numbers or the receptor half
      life. Incubation of rat liver plasma membranes with human, bovine or rat blood
      sera totally blocked alpha-subunit proteolysis both in the absence or presence of
      insulin. The three major serum proteinase inhibitors, alpha 1-antitrypsin, alpha
      2-macroglobulin and antithrombin III, blocked alpha-subunit proteolysis of the
      insulin receptor to a varying extent. alpha 1-antitrypsin exhibited the highest
      potency, decreasing the amount of 120-kDa product by 70%. When both alpha 1
      antitrypsin and antithrombin III were present, inhibition increased to 85%. Thus,
      the absence of proteolysis of the hepatic insulin receptor in vivo could be
      mostly accounted for by the antiproteolytic activity of blood serum. These
      findings suggest that insulin receptor alpha-subunit proteolysis does not
      represent a mechanism involved in the down-regulation of the insulin receptor in
      liver.

PMID- 7588721
TI  - Evidence for sodium dodecyl sulfate/protein complexes adopting a necklace
      structure.
AB  - Structural analysis by cryo-electron microscopy and small-angle X-ray scattering
      of ten sodium dodecyl sulfate/protein complexes in 25 mM Tris/HCl, 0.192 M
      glycine, pH 8.3, showed necklace-like structures of spherical micelles dispersed
      along the unfolded peptide chain. The micelles of most SDS/protein complexes had
      a constant diameter (approximately 6.2 nm), slightly larger than pure SDS
      micelles (approximately 5.7 nm), all micelles possessing a degree of surface
      roughness. The micelle-associated polypeptide is mostly situated at the interface
      of the sulfate head groups and hydrocarbon core, intruding into the core rather
      than outward from the surface. Proteins with a molecular mass less than about 20
      kDa formed complexes with a single SDS micelle. Multi-micellar SDS/protein
      complexes had centre-to-centre intermicellar distances in the range 7.0-12.0 nm.
      Our findings on the constancy of micellar size, number of micelles/complex, and
      the relationship between the degree of occupancy of micelles and a polypeptide's
      molecular mass, have enabled us to speculate on the correlation between the
      electrophoretic mobility of a polypeptide in SDS/PAGE and its molecular mass. The
      anomalous electrophoretic behaviour observed for the sodium dodecyl
      sulfate/histone H5 complex is accounted for by the large micelle of its complex.

PMID- 7588715
TI  - Identification of factor-XIIIa-reactive glutaminyl residues in the propolypeptide
      of bovine von Willebrand factor.
AB  - von Willebrand factor is a large multimeric plasma protein which plays important
      roles in platelet aggregation, blood coagulation and probably also in the
      adhesion of endothelial cells. A 100-kDa propeptide, called the propolypeptide of
      von Willebrand factor (pp-vWF), is generated during biosynthesis. We found that
      pp-vWF served as a substrate for transglutaminases including human factor XIIIa
      and guinea pig liver transglutaminase [Usui, T., Takagi, J. & Saito, Y. (1993) J.
      Biol. Chem. 268, 12311-12316]. As such, it could form cross-linked copolymers
      with the extracellular matrix protein, laminin, making it all the more likely
      that pp-vWF plays a role in cell adhesion phenomena [Takagi, J., Sudo, Y., Saito,
      T. & Saito, Y. (1994) Eur. J. Biochem. 222, 861-867]. In this work, we identified
      the Gln residues in pp-vWF specifically reacting with blood coagulation factor
      XIIIa as amine acceptors. The fluorescent amine, dansylcadaverine, was employed
      for labeling the enzyme-reactive sites of the protein. Following partial
      proteolysis, fragments containing the labeled Gln residues were isolated by
      passage through an anti-dansyl affinity chromatographic column. Amino acid
      sequence analyses of the fragments revealed that, out of about 40 Gln residues in
      pp-vWF, only four could be modified in the factor-XIIIa-catalyzed reaction.

PMID- 7588717
TI  - Cell cycle, differentiation and tissue-independent expression of ribosomal
      protein L37.
AB  - A unique human cDNA (hG1.16) that encodes a mRNA of 450 nucleotides was isolated
      from a subtractive library derived from HeLa cells. The relative expression level
      of hG1.16 during different cell-cycle phases was determined by Northern-blot
      analysis of cells synchronized by double-thymidine block and serum
      deprivation/refeeding. hG1.16 was constitutively expressed during all phases of
      the cell cycle, including the quiescent phase when even most constitutively
      expressed genes experience some suppression of expression. The expression level
      of hG1.16 did not change during terminal differentiation of myoblasts to
      myotubes, during which cells become permanently post-mitotic. Examination of
      other tissues revealed that the relative expression level of hG1.16 was
      constitutive in all embryonic mouse tissues examined, including brain, eye,
      heart, kidney, liver, lung and skeletal muscle. This was unusual in that
      expression was not down-modulated during differentiation and did not vary
      appreciably between tissue types. Analysis by inter-species Northern-blot
      analysis revealed that hG1.16 was highly conserved among all vertebrates studied
      (from fish to humans but not in insects). DNA sequence analysis of hG1.16
      revealed a high level of similarity to rat ribosomal protein L37, identifying
      hG1.16 as a new member of this multigene family. The deduced amino acid sequence
      of hG1.16 was identical to rat ribosomal protein L37 that contained 97 amino
      acids, many of which are highly positively charged (15 arginine and 14 lysine
      residues with a predicted M(r) of 11,065). hG1.16 protein has a single C2-C2 zinc
      finger-like motif which is also present in rat ribosomal protein L37. Using
      primers designed from the sequence of hG1.16, unique bovine and rat cDNAs were
      also isolated by 5'-rapid-amplification of cDNA ends. DNA sequences of bovine and
      rat G1.16, clones were 92.8% and 92.2% similar to human G1.16 while the deduced
      amino acid sequences derived from bovine and rat cDNAs each differed by a single
      amino acid from the sequence of hG1.16 and the published rat L37 sequence.
      Southern-blot analysis revealed that hG1.16 exists in multiple copies in human,
      rat and mouse genomes. These G1.16 clones encode unique human, rat and bovine
      members of the ribosomal protein L37 gene family, which are constitutively
      expressed even during transitions from quiescence to active cell proliferation or
      terminal differentiation, in all tissues and all vertebrates investigated.

PMID- 7588722
TI  - Structural influence of calcium on the heme cavity of cationic peanut peroxidase
      as determined by 1H-NMR spectroscopy.
AB  - The cationic isozyme of peanut peroxidase (CPRx) is one of many peroxidases which
      requires calcium for enzyme activity. It has been previously shown that it
      requires 2 mol calcium to coordinate to 1 mol CPRx, and its related peroxidases
      from the basidiomycete Phanerochaete chrysosporium (LiP) and isozyme C of
      horseradish (HRPc). X-ray crystallographic studies of LiP have shown that calcium
      is ligated near the C-terminus of helices proximal and distal to the heme, where
      it has been suggested to maintain the active site. To determine if such a
      mechanism was possible in CPRx, high resolution 1H-NMR spectroscopy was used to
      study the effect of calcium on the environment of its heme group and the
      coordinating histidine residues. The low-spin cyano complex of the enzyme
      (CPRxCN) was studied in order to assign the majority of the resonances arising
      from the protons in the heme pocket in both the presence and absence of bound
      calcium ions using two dimensional nuclear Overhauser effect spectroscopy
      (NOESY). The two calcium ions present in CPRxCN were removed by a non-denaturing
      method and a calcium titration was performed and monitored by 1H-NMR
      spectroscopy. These studies showed that the binding of both calcium ions in CPRx
      influenced the heme environment in a similar manner (Kd = 0.1 microM). In
      particular, calcium-dependent changes in several heme resonances and the proximal
      and distal histidine residues suggest that calcium binding to CPRx causes some
      reorientation of these residues with respect to the active site.

PMID- 7588720
TI  - Reversible super-reduction of the cubane [4Fe-4S](3+;2+;1+) in the high-potential
      iron-sulfur protein under non-denaturing conditions. EPR spectroscopic and
      electrochemical studies.
AB  - The reversible 2 x 1 e- reduction of the cubane cluster from oxidized to reduced
      to super-reduced states ([4Fe-4S]3+<-->[4Fe-4S]2+<-->[4Fe-4S]1+) was studied in
      high-potential iron-sulfur proteins (HiPIPs). Super-reduction to the 1+ state was
      not observed in any of the seven HiPIPs tested during cyclic voltammetry (down to
      -0.95 V). However, equilibration at low potential (pH 7.5) of Rhodopila
      globiformis HiPIP yields a transient peak around -0.47 V due to the oxidation of
      super-reduced HiPIP adsorbed at the electrode. The peak area depends on the
      equilibration potential according to a one-electron Nernst curve with a half-wave
      potential at -0.91 V. Reduction of R. globiformis HiPIP with titanium
      (III)citrate at pH 9.5 is very slow [pseudo-first-order half-life of 23 min with
      a 100-fold excess Ti(III)] but is reversible, and the EPR spectrum with g values
      of 2.04 and 1.92 is similar to that of reduced [4Fe-4S]1+ ferredoxins. Chemical
      or electrochemical reoxidation of the super-reduced form resulted in an EPR
      spectrum with g parallel = 2.12 and g perpendicular = 2.03, i.e. identical to
      that of oxidized HiPIP. From the equilibrium concentration of super-reduced HiPIP
      at a low concentration of Ti(III), a reduction potential of -0.64 V can be
      estimated. Super-reduction of the large HiPIP (iso-2) from Rhodospirillum
      salinarum is also possible with Ti(III)(gz = 2.05) but the super-reduced state is
      unstable. No super-reduction with Ti(III) was observed for the other HiPIPs. The
      difference between the electrochemically observed reduction potential and
      oxidation potential is explained by a fast and reversible conformational change
      upon super-reduction. The rate of super-reduction with Ti(III) is limited by the
      small amount (0.1%) of HiPIP in the 2+ state with the super-reduced conformation.

PMID- 7588718
TI  - A cytochrome-b5-containing fusion protein similar to plant acyl lipid
      desaturases.
AB  - The similarity between oleate and linoleate desaturase sequences from several
      plants was used to construct degenerate oligonucleotide primers for PCR
      experiments with cDNA transcribed from mRNA of ripening sunflower embryos. A DNA
      fragment was amplified and sequenced. Specific primers derived from this partial
      sequence were used for rapid amplification of the 3'- and 5'-ends of this cDNA.
      With appropriate primers derived from these sequences, a full-length clone of
      1377 bp was amplified by PCR which, after sequencing, showed an open reading
      frame of 458 amino acids corresponding to a putative protein of about 52 kDa.
      Comparison with other desaturases showed the conserved three histidine boxes and
      the characteristic hydropathy profile of membrane-bound desaturases, but the
      amino acid identity was restricted to 18% and the N-terminal region was about 100
      amino acids longer. This N-terminal extension showed high similarity with
      cytochrome b5 and, accordingly, the whole sequence can be considered as coding
      for a fusion protein between cytochrome b5 and a desaturase-like enzyme.
      Furthermore, we detected a similar cytochrome b5 fold in the previously sequenced
      delta 9 acyl-CoA desaturase from yeast, but in this enzyme it was located at the
      C-terminus. An alignment of these fusion proteins with other heme-binding
      proteins revealed desaturases to be novel members of the cytochrome b5
      superfamily. A truncated DNA representing 366 bp of the 5'-end was amplified from
      the cDNA clone and expressed in Escherichia coli. The truncated cDNA coded for a
      soluble protein of about 12 kDa as shown by SDS/PAGE and N-terminal sequencing.
      The enriched recombinant protein exhibited redox absorbance spectra
      characteristic of plant microsomal cytochrome b5.

PMID- 7588719
TI  - A plant acyltransferase involved in triacylglycerol biosynthesis complements an
      Escherichia coli sn-1-acylglycerol-3-phosphate acyltransferase mutant.
AB  - The second acylation reaction in glycerolipid biosynthesis is catalyzed by an sn
      1-acylglycerol-3-phosphate acyltransferase. The enzyme of Limnanthes douglasii
      involved in triacylglycerol synthesis has an unusual specificity for very long
      chain acyl groups in both of its substrates, namely acyl-CoA and sn-1
      acylglycerol-3-phosphate, and causes the enrichment of erucoyl groups in the sn-2
      position of the seed oil of this plant species. We have isolated a cDNA clone
      encoding this embryo-specific, microsomal acyltransferase via heterologous
      complementation of an Escherichia coli mutant deficient in sn-1-acylglycerol-3
      phosphate acyltransferase activity. The open reading frame of the cDNA insert
      encodes a protein with a length of 281 amino acids, with three predicted membrane
      spanning domains and of about 31.7 kDa. The sequence exhibits substantial
      sequence similarity to the sn-1-acylglycerol-3-phosphate acyltransferase of E.
      coli. The corresponding transcript was detectable in developing embryos but not
      in leaves of L. douglasii, and expression of the open reading frame in E. coli
      caused sn-1-acylglycerol-3-phosphate acyltransferase activity which showed
      properties different from those of the bacterial acyltransferase but typical of
      the L. douglasii enzyme involved in triacylglycerol biosynthesis.

PMID- 7588723
TI  - The mutation Asp69-->Ser affects the chaperone-like activity of alpha A
      crystallin.
AB  - alpha-Crystallins are members of the family of small heat-shock proteins. The
      conformation and mode of action of these 'junior chaperones' are unknown. To
      investigate the structure and chaperone-like activity, four mutants of bovine
      alpha A-crystallin were generated by site-directed mutagenesis. In comparison
      with wild-type alpha A-crystallin, the D69S mutant, in which a highly conserved
      charged residue has been replaced, forms larger multimers and displays a
      threefold reduced heat-protection capacity. The conformation and thermal
      stability of this mutant are not noticeably affected. Three other mutations,
      replacing hydrophobic by uncharged hydrophilic residues, were aimed at disturbing
      hydrophobic intersubunit interactions. None of these mutations resulted in major
      structural perturbations and only minor differences in heat-protective capacity
      were observed. Although it is assumed that small heat-shock proteins interact
      with denaturing proteins via their hydrophobic surfaces, this study clearly shows
      that charged residues in alpha-crystallin can also influence the efficiency of
      substrate binding.

PMID- 7588716
TI  - m7GpppG cap dependence for efficient translation of Drosophila 70-kDa heat-shock
      protein (Hsp70) mRNA.
AB  - To investigate whether preferential translation of the heat-shock mRNAs occurs
      via cap-independent translation, the requirement for the m7GpppG cap structure
      for efficient translation of 70-kDa heat-shock-protein (Hsp70) mRNA was
      quantified by in vitro translation and by in vivo translation following
      electroporation. Hsp70 mRNA was transcribed in vitro with and without a cap
      structure. Translation in the rabbit reticulocyte or wheat germ lysate was
      reduced about 70% when the cap was absent. For comparison, translation of
      uncapped encephalomyocarditis virus 5'-untranslated-region-containing mRNA was
      equal to or greater than capped mRNA, whereas translation of several non-heat
      shock mRNAs was reduced by 85-95% when capping was omitted. Cap-dependent
      translational stimulation of Hsp70 is not due to increased stability, is not a
      kinetic effect, and requires the methylated GpppG. To confirm the in vitro
      analyses, capped and uncapped mRNA were introduced into Drosophila tissue culture
      cells by electroporation, followed by heat shock. Paralleling the in vitro
      results, uncapped Hsp70 mRNA translation was 70-80% reduced relative to the
      capped form. Complementary experiments in which eIF-4 was inactivated in vitro
      using either m7GTP cap analogue or foot-and-mouth-disease virus L protease
      expression likewise indicated that the cap-dependent translation pathway is
      required for optimal Hsp mRNA translation. Since cellular Hsp70 mRNA translation
      during heat shock is very efficient, it is unlikely that translation via a cap
      independent pathway is the principal basis for preferential translation.

PMID- 7588714
TI  - Molecular and biochemical characterization of a Plasmodium falciparum cyclophilin
      containing a cleavable signal sequence.
AB  - The immunosuppressive drug cyclosporin A (CsA) inhibits the growth of malaria
      parasites in vitro and in vivo. Cyclosporin A exerts its immunosuppressive effect
      in T lymphocytes by binding to cyclophilin (CyP), a peptidylprolyl cis-trans
      isomerase (PPIase). It is believed that the cyclosporin/cyclophilin complex
      inhibits a Ca(2+)-activated protein phosphatase, calcineurin, involved in T-cell
      activation. A cDNA encoding a cyclophilin of the human malaria parasite
      Plasmodium falciparum has been isolated as a step in the elucidation of the
      mechanism of antimalarial action of CsA. This cDNA, termed PfCyP, encodes a
      protein of 195 amino acids which has highest similarity with the Candida albicans
      (73.1%) and the Drosophila melanogaster (73.1%) cytoplasmic cyclophilins. A
      Northern blot reveals an approximately 900-bp nucleotide transcript that is
      consistent with the predicted size of the encoded polypeptide. The predicted
      PfCyP protein has a putative endoplasmic-reticulum-directed signal sequence at
      its N-terminus and two potential N-linked glycosylation sites. Expression of
      PfCyP RNA in an in vitro translation/translocation system reveals that the PfCyP
      protein is translocated across microsomes, that the signal peptide is cleaved and
      that the PfCyP protein is glycosylated at two sites. The PfCyP cDNA open reading
      frame coding for the predicted mature protein has been expressed in Escherichia
      coli. The purified recombinant protein is an active PPIase (kcat/Km = 2.3 x 10(6)
      s-1 M-1); this enzymic activity is inhibited by CsA (IC50 = 10 nM). The PfCyP
      protein has thus the same sensitivity to CsA as the PPIase activity associated
      with P. falciparum extracts [Bell, A. et al. (1994) Biochem. Pharmacol. 48, 495
      503] suggesting that PfCyP may be responsible for the PPIase activity in those
      extracts. If different cyclophilins exist in P. falciparum, we conclude that
      either the PfCyP protein is the major cyclophilin detected in the parasite or
      that there are other cyclophilins with similar susceptibilities to CsA.

PMID- 7588725
TI  - Interaction of a fluorescent analog of N-deacetyl-N-methyl-colchicine (colcemid)
      with liver alcohol dehydrogenase.
AB  - The evidence for specific binding of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-
      colcemid (NBD-colcemid), a fluorescent analog of colcemid (N-deacetyl-N-methyl
      colchicine), to liver alcohol dehydrogenase is presented. Alcohol dehydrogenase
      bound NBD-colcemid in a time-dependent manner, enhanced the fluorescence
      intensity, and caused a large blue shift of the emission maximum of the free
      drug. The specificity of binding was determined for both the colchicine nucleus
      and the NBD moiety. The binding was not affected by the presence of alcohol or
      NAD in the reaction mixture. Preincubation of horse liver alcohol dehydrogenase
      with colcemid inhibited the binding to a considerable extent. NBD-colcemid
      inhibited the enzymic activity of alcohol dehydrogenase in a mixed-type
      noncompetitive mode with a Ki value of 32 microM, whereas colcemid showed
      noncompetitive inhibition with a Ki of 100 microM. The association rate constant
      of NBD-colcemid binding with liver alcohol dehydrogenase was 587 M-1 s-1 at 25
      degrees C. The stoichiometry and dissociation constant of the binding reaction
      were 0.62/dimer and 12 microM, respectively. Donor quenching experiments showed
      that both tryptophans of alcohol dehydrogenase transferred energy to the bound
      NBD-colcemid. Thus, this study reports the binding of a colchicine analog to a
      protein other than tubulin with high affinity. It is concluded that NBD-colcemid
      binding to dehydrogenases is a general phenomenon, but the common structural
      element(s) that is responsible for the binding activity, and which exists among
      tubulin and dehydrogenases, has yet to be determined.

PMID- 7588726
TI  - Crystal and molecular structure at 0.16-nm resolution of the hybrid Bacillus endo
      1,3-1,4-beta-D-glucan 4-glucanohydrolase H(A16-M).
AB  - H(A16-M) is a hybrid endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase from Bacillus.
      Its crystal structure was refined using synchrotron X-ray diffraction data up to
      a maximal resolution of 0.16 nm. The R value of the resulting model is 14.3%
      against 21,032 reflections > 2 sigma. 93% of the amino acid residues are in the
      most favorable regions of the Ramachandran diagram, and geometrical parameters
      are in accordance with other proteins solved at high resolution. As shown earlier
      [Keitel, T., Simon, O., Borriss, R. & Heinemann, U. (1993) Proc. Natl Acad. Sci.
      USA 90, 5287-5291], the protein folds into a compact jellyroll-type beta-sheet
      structure. A systematic analysis of the secondary structure reveals the presence
      of two major antiparallel beta-sheets and a three-stranded minor mixed sheet.
      Amino acid residues involved in catalysis and substrate binding are located
      inside a deep channel spanning the surface of the protein. To investigate the
      stereochemical cause of the observed specificity of endo-1,3-1,4-beta-D-glucan 4
      glucanohydrolases towards beta-1,4 glycosyl bonds adjacent to beta-1,3 bonds, the
      high-resolution crystal structure has been used to model an enzyme-substrate
      complex. It is proposed that productive substrate binding to the subsites p1, p2
      and p3 of H(A16-M) requires a beta-1,3 linkage between glucose units bound to p1
      and p2.

PMID- 7588724
TI  - Abnormally high pKa of an active-site glutamic acid residue in Bacillus circulans
      xylanase. The role of electrostatic interactions.
AB  - The active site of Bacillus circulans xylanase (1,4-beta-D-xylanohydrolase, EC
      3.2.1.8) contains two glutamic acid residues, Glu78 and Glu172, which are crucial
      for the catalytic activity of the enzyme. Fourier-transform infrared spectroscopy
      was used to determine the ionization state of these residues as a function of pH.
      For the wild-type enzyme, titration of one of the carboxylate groups occurs at pH
      6.8. This titration is absent in the Glu78-->Gln and Glu172-->Gln variants of the
      enzyme. This, together with crystallographic data, indicates that Glu172 has an
      abnormally high pKa of 6.8, caused largely by electrostatic interactions of this
      residue with the proximal Glu78. Differential scanning calorimetry experiments
      with the wild-type xylanase and a number of its mutants have shown that the
      presence of two nearby carboxyl groups results in a pH-dependent destabilization
      of the protein structure.

PMID- 7588728
TI  - Inhibitory effect of annexin V on protein kinase C activity in mesangial cell
      lysates.
AB  - Annexin V belongs to a large family of calcium-binding and phospholipid-binding
      proteins and may act as an endogenous regulator of the protein kinase C (PKC)
      activity. This study examines the effect of annexin V on the in vitro PKC
      activity in cultured mesangial cells using histone H1, the peptide [Ser25]PKC-(19
      31), or endogenous proteins as substrates. The SDS/PAGE pattern of 32P-labeled
      mesangial proteins showed that the calcium-independent PKC [(n+a)PKC]
      phosphorylated several proteins from 70 kDa to 40 kDa and 22 kDa to 15 kDa. Three
      additional proteins from 34 kDa to 29 kDa, including annexin I and its
      proteolytic forms, were detected after activation of calcium-dependent PKC
      (cPKC). Increasing concentrations of annexin V did not alter the phosphorylation
      of (n+a)PKC substrates. By contrast, specific phosphorylation of proteins and
      annexin I by cPKC, was reduced in a dose-dependent manner. Addition of high
      concentration of calcium and phosphatidylserine did not reverse the inhibitory
      effect of annexin V. Annexin V also inhibited the phosphorylation of histone H1
      or peptide [Ser25]PKC-(19-31) by cPKC. Moreover, removal of annexin V from
      cytosols increased the annexin I phosphorylation by these isoforms. From these
      results, we propose that annexin V may regulate the signal-transduction pathway
      involving the activation of cPKC, as they act in vitro as an inhibitor of these
      kinases.

PMID- 7588727
TI  - The roles of Tyr70 and Tyr225 in aspartate aminotransferase assessed by analysing
      the effects of mutations on the multiple reactions of the substrate analogue
      serine o-sulphate.
AB  - Aspartate aminotransferase catalyses multiple reactions of the glutamate
      analogue, serine O-sulphate. The predominant reaction is beta-elimination of
      sulphate to give aminoacrylate (kcat = 13 s-1 for the Escherichia coli enzyme)
      which may either hydrolyse to pyruvate and ammonia, or react covalently with the
      enzyme and inactivate it (kinact = 1.1 x 10(-3) s-1). Serine O-sulphate also
      undergoes a transamination reaction that converts the enzyme to its pyridoxamine
      form (kcat = 0.11 s-1). Tyr70 and Tyr225, each of which forms a hydrogen bond
      with the coenzyme, were substituted with methionine and phenylalanine,
      respectively. The Y225F mutation does not affect beta-elimination but reduces the
      rates of transamination and inactivation about 70-fold and 3-fold, respectively.
      Apparently, Tyr225 is not essential for the steps leading to and including
      abstraction of the proton from C alpha of the substrate. It is argued that the
      Y225F mutation interferes with ketimine hydrolysis. The Y70M mutation affects all
      three reactions, beta-elimination being about fourfold slower, transamination 340
      fold slower, and inactivation being 1.4 times faster than in the wild-type
      enzyme. It is proposed that a hydrogen bond from Tyr70 positions Lys258 for
      protonation of the quinonoid intermediate at C4' and that, although the full
      kinetic contribution of this interaction is only revealed in the multiple
      reactions of serine O-sulphate, the same interaction is equally important in
      increasing the reaction specificity for transamination of the natural substrates.

PMID- 7588730
TI  - Effect of 1-O-octadecyl-2-O-methyl-glycerophosphocholine on phosphatidylcholine
      and phosphatidylethanolamine synthesis in MCF-7 and A549 cells and its
      relationship to inhibition of cell proliferation.
AB  - The role of perturbation of lipid synthesis in the inhibition of cell
      proliferation by OctMeGroPCho was investigated with sensitive (MCF-7) and
      resilient (A549) cell lines. It inhibited de novo synthesis of
      phosphatidylcholine in both cells but increased triacylglycerol synthesis in A549
      cells and phosphatidylethanolamine, phosphatidic acid and diacylglycerol
      synthesis in MCF-7 cells. The inhibition of synthesis of CDP-choline metabolites
      in MCF-7 cells and phosphatidylcholine biosynthetic enzyme activities in vitro by
      OctMeGroPCho suggests that direct inhibition of phosphocholine
      cytidylyltransferase may contribute to the observed inhibition of
      phosphatidylcholine synthesis. The activation of phosphoethanolamine
      cytidylyltransferase and ethanolamine phosphotransferase activities by
      OctMeGroPCho in vitro and increased production of CDP-ethanolamine suggest that
      stimulation of the above enzymes by OctMeGroPCho in the cells is responsible for
      the increased phosphatidylethanolamine synthesis. The apparent effect of
      OctMeGroPCho on intracellular lipid-metabolising enzymes is a strong indication
      that it may be widely distributed intracellularly and not just confined to the
      plasma membrane. The decrease in phosphatidylcholine synthesis by OctMeGroPCho in
      MCF-7 cells was prevented by co-incubation with oleic acid without any effect on
      the inhibition of cell growth. Although OctMeGroPCho resulted in similar
      decreases in phosphatidylcholine content in both cells, this did not affect the
      proliferation of A549 cells. The above results indicate that, although
      OctMeGroPCho has profound effects on lipid metabolism, these changes are not
      responsible for the inhibition of proliferation observed in MCF-7 cells.

PMID- 7588731
TI  - Mechanism of dimer formation of the 90-kDa heat-shock protein.
AB  - This study describes the mechanism of homodimer formation of the 90-kDa heat
      shock protein (HSP90). In eukaryotic cells, there are two HSP90 isoforms, alpha
      and beta, encoded by two separate genes. HSP90 alpha exists predominantly as a
      homodimer, HSP90 beta mainly as a monomer. Analysis by native PAGE revealed that
      bacterially expressed HSP90 alpha fused to glutathione S-transferase (GST)
      existed as a high-molecular-mass oligomer, and was converted to a homodimer
      following removal of the fusion enzyme by thrombin cleavage. A deletion mutant,
      HSP90 alpha D44-603, formed a monomer and an N-terminal truncated mutant, HSP90
      alpha 533-732, existed as a dimer, indicating that the dimer-forming ability
      resides somewhere in the C-terminal 200 amino acids. Limited proteolysis of the C
      terminal 200 amino acids of HSP90 alpha with chymotrypsin produced the C-terminal
      16-kDa fragment (Met628/Ala629-Asp732) and its adjacent more N-terminal 13-kDa
      fragment (Val542-Tyr627/Met628). Size-exclusion HPLC and two-dimensional PAGE
      analyses demonstrated that these two chymotryptic fragments bound each other. The
      C-terminal 198 amino acids as well as the full-length form of HSP90 beta revealed
      a lower dimer-forming activity than HSP90 alpha. Expression of the chimeric
      proteins at the C-terminal 198 amino acids of the alpha and beta isoforms further
      indicated that the 16 amino acid substitutions locating between amino acids 561
      and 685 account for the impeded dimerization of HSP90 beta. A leucine zipper
      motif (Met402-Leu423) was unlikely to be involved in the dimer formation. Taken
      together, these results indicate that the dimeric structure of HSP90 alpha is
      mediated by the C-terminal 191 amino acids and consists of duplicate interactions
      of the C-terminal region (Met628/Ala629-Asp732) of one subunit and the adjacent
      more N-terminal region (Val542-Try627/Met628) of the other subunit.

PMID- 7588729
TI  - Structure of the N-linked oligosaccharides from tridacnin, a lectin found in the
      haemolymph of the giant clam Hippopus hippopus.
AB  - Tridacnin, a glycoprotein lectin, was isolated from the symbiotic marine clam
      Hippopus hippopus and the structure of its major N-glycan chains determined.
      Tridacnin contains only N-linked glycans which were quantitatively cleaved by
      peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Following
      purification by anion-exchange HPLC, the structures of the oligosaccharides were
      established using a combination of electrospray ionisation mass spectrometry, 1H
      NMR spectroscopy and linkage analysis. The N-glycans are primarily of the
      oligomannose type but, in addition, some contain a novel 6-O-Me group on the
      terminal mannose residue of the chain. The N-glycan chains had the following
      structures. [formula: see text]

PMID- 7588732
TI  - Cloning and properties of a novel natriuretic peptide receptor, NPR-D.
AB  - A novel natriuretic peptide receptor, which we have termed natriuretic peptide
      receptor D (NPR-D), has been cloned and characterized. cDNAs related to the
      natriuretic peptide receptor (NPR) were amplified by PCR from a template of
      poly(A)-rich RNA isolated from the eel gill. Sequencing of the PCR products
      revealed the presence of a new clone that showed about 70% sequence identity to
      the eel type-C receptor, NPR-C. The PCR fragment was used to determine the tissue
      distribution of the new NPR-D message by an RNase protection assay, which gave
      the strongest signal in brain samples, and then used to screen a brain library to
      obtain a full-length cDNA clone. The cDNA clone predicted a protein of 500 amino
      acids containing a signal sequence and a hydrophobic transmembrane segment. The
      predicted sequence also contained the NPR motif which is essential for the
      binding of natriuretic peptides. The protein NPR-D was expressed in COS cells and
      shown to have high affinities for eel and rat natriuretic peptides. The newly
      cloned NPR-D has a short cytoplasmic tail; in this respect, NPR-C and NPR-D are
      very similar and form a subfamily of the NPR family. Affinity labeling indicated
      that NPR-D exists as a disulfide-linked tetramer. This is a marked contrast to
      the homodimeric structure of NPR-C. HS-142-1, a non-peptide natriuretic peptide
      receptor antagonist of microbial origin previously shown to be selective for the
      guanylate-cyclase-coupled receptors NPR-A and NPR-B, competitively inhibited the
      binding of 125I-labeled eel natriuretic peptide to eel NPR-D, whereas it did not
      affect the binding activity of eel NPR-C, suggesting that HS-142-1 is an
      antagonist that recognizes the tetrameric structures of NPR since the guanylate
      cyclase-coupled receptors have also been demonstrated to exist as tetramers.

PMID- 7588735
TI  - The effect of cross-linking of the two heads of porcine aorta smooth muscle
      myosin on its conformation and enzymic activity.
AB  - The two heads of porcine aorta smooth muscle myosin can be cross-linked by a
      disulfide bridge between the two 17-kDa essential light chains with 5,5'
      dithiobis(2-nitrobenzoic acid) [Katoh, T., Tanahashi, K., Hasegawa, Y. & Morita,
      F. (1995) Eur. J. Biochem. 227, 459-465]. When the cross-linked myosin sample was
      visualized by rotary shadowing, the two heads of myosin molecules appeared
      predominantly to adhere to each other. The cross-linking of dephosphorylated
      myosin in the presence of ATP was greatly inhibited by a decrease in the
      concentration of NaCl from 0.4 M to 0.15 M, suggesting that the cross-linking of
      the two heads was suppressed in 10S myosin. However, the fraction of
      dephosphorylated myosin in a filamentous state at 0.1 M NaCl in the presence of 1
      mM ATP was increased from 33% to 83% by the cross-linking. The cross-linking of
      the two heads might inhibit the formation of the 10S conformation, leading to the
      increase in the fraction of filamentous myosin. The filaments of the cross-linked
      myosin sample were visualized by electron microscopy and appeared morphologically
      similar to those of uncross-linked myosin. The ATPase activity of the cross
      linked dephosphorylated myosin sample was more than three times as high as that
      of an uncross-linked control. The increase in the activity may be related to the
      increase in the fraction of filamentous myosin caused by the cross-linking. The
      ATPase activity of dephosphorylated myosin in the presence of actin was increased
      more than twofold by the cross-linking, but the activity of phosphorylated myosin
      was affected only slightly. The degree of phosphorylation-dependent regulation of
      actin-activated ATPase activity decreased with an increase in the degree of cross
      linking and was extrapolated to zero at 100% cross-linking. Superprecipitation of
      acto-cross-linked dephosphorylated myosin was activated, while that of acto-cross
      linked phosphorylated myosin was inhibited only slightly. These results suggest
      that the freedom of each head in myosin molecules may be required to keep the
      ATPase activity and superprecipitation of acto-dephosphorylated myosin low but
      not for keeping these activity levels high in acto-phosphorylated myosin.

PMID- 7588733
TI  - Purification and biochemical characterization of myomesin, a myosin-binding and
      titin-binding protein, from bovine skeletal muscle.
AB  - We report a method for isolating homogeneous myomesin from mammalian skeletal
      muscle. The identity of the purified bovine protein was confirmed by its
      reactivity with myomesin-specific monoclonal antibodies and with polyclonal
      antibodies raised against peptides derived from the amino-terminal and carboxy
      terminal ends of the sequence predicted by the human myomesin cDNA. All partial
      sequences obtained from bovine myomesin can be aligned along the human sequence
      predicted by its cloned cDNA. Electron microscopy of myomesin revealed short
      flexible rods with a molecular length of about 50 nm. Circular dichroism spectra
      showed a high degree of beta structure as expected for a member of the
      immunoglobulin superfamily of proteins. Alignment of the sequences of the class I
      and II domains of myomesin with the sequences of domains of known three
      dimensional structure provides a more detailed model of myomesin. In agreement
      with this view, the cleavage sites observed by limited proteolysis locate
      primarily between individual domains. In a solid-phase overlay assay myomesin
      specifically bound to the myosin rod and to light meromyosin (LMM), but not to
      the carboxy-terminal 30-kDa fragment of LMM. The myosin-binding site seemed to be
      confined to the amino-terminal 240 residues of the molecule. The cross-reactivity
      of myomesin with the phosphorylation-dependent monoclonal neurofilament antibody
      NE14 [Shaw, G.E., Debus, E. & Weber, K. (1984) Eur. J. Cell Biol. 34, 130-136]
      was analyzed. NE14 reactivity of myomesin was abolished by alkaline phosphatase.
      Reactivity of the antibody on stable proteolytic fragments of myomesin showed
      that the phosphorylation site must reside within the carboxy-terminal 60
      residues.

PMID- 7588736
TI  - Purification and properties of codeinone reductase (NADPH) from Papaver
      somniferum cell cultures and differentiated plants.
AB  - Codeinone reductase (NADPH), which catalyzes the stereospecific reduction of (
      )codeinone to (-)codeine, was detected and purified to electrophoretic
      homogeneity from a cytosolic fraction of Papaver somniferum L. cell cultures. The
      purification involved ammonium sulfate precipitation (40-80%), affinity
      chromatography (matrex red A), gel filtration (fractogel TSK HW 55S), affinity
      chromatography (fractogel TSK AF Blue), ion-exchange chromatography (DEAE
      Sephacel) and native PAGE. The purified codeinone reductase was found to be a
      monomeric protein of 35 +/- 1 kDa that is highly substrate-specific, reducing
      only the C6 oxo group of codeinone and morphinone as well as a few analogues. The
      physiological forward reaction has a pH optimum at 7.0, the reverse reaction at
      9.1. The temperature optimum is at 40 degrees C and the isoelectric point (p1) at
      4.4. The apparent Km values (forward reaction) for codeinone and NADPH are 23
      microM and 168 microM, respectively. Using capsule tissue of differentiated P.
      somniferum plants as an enzyme source, two codeinone reductase (NADPH) isoenzymes
      were detected and purified to homogeneity. These isoenzymes could not be
      separated for characterization and showed slightly different kinetic features (Km
      values: codeinone 9 microM; NADPH 81 microM) compared with the cell culture
      enzyme.

PMID- 7588734
TI  - Expression, purification and characterization of the enzyme II mannitol-specific
      domain from Staphylococcus carnosus and determination of the active-site cysteine
      residue.
AB  - The C-terminal B domain of mannitol-specific enzyme II (enzyme IIB) of the
      phosphoenolpyruvate-dependent phosphotransferase system for mannitol from
      Staphylococcus carnosus was subcloned, purified and characterized. In
      Staphylococcal cells, mannitol-specific enzyme II is composed of a soluble A
      domain (EIIA) and a transmembrane C domain transporter with a fused enzyme IIB
      (IIB) domain. We purified large amounts of the IIB domain as an in-frame fusion
      with six histidine residues. Here, we show that the domain is stable and can be
      phosphorylated by phosphoenolpyruvate and the phosphotransferase components. It
      is a dimer over a wide range of pH values and salt conditions. Differences
      between the published nucleotide sequence data and the mass-spectroscopic data
      obtained with the purified protein lead to anewed nucleotide sequencing of the
      gene. Two errors in the original proposed sequence were found, the correction of
      the second error leading to a frame shift that adds 10 amino acids to the deduced
      amino acid sequence. The mass of the phosphorylated domain is 20,068 Da, 80 Da
      more than the mass of the unphosphorylated domain, therefore, no other residues,
      such as COOH side chains, are directly involved in an additional phosphate
      linkage concerning the IIB domain. 31P-NMR experiments as well as chemical
      modification proved that Cys429 is the phosphoamino acid. Titration of the
      phosphorylated domain during 31P-NMR did not lead to the typical shift for the
      protonation of the thiophosphate in the resonance spectrum. Thus, the
      thiophosphate remains in the twofold negatively charged state.

PMID- 7588737
TI  - A two-binding-site kinetic model for the ribonuclease-T1-catalysed
      transesterification of dinucleoside phosphate substrates.
AB  - Ribonucleases have been found to have subsites that confer large rate
      enhancements but do not contribute to substrate binding. In this study, we
      present a kinetic model that formally explains how subsite binding energy is
      converted into chemical activation energy. The proposed mechanism takes into
      account a primary specificity site and a subsite, both of which must be occupied
      for chemical turnover. An unstable reaction intermediate is formed upon binding
      of the polymeric substrate monomers at the corresponding subsites. The structure
      of this reaction intermediate resembles the transition state of the catalysed
      transphosphorylation reaction. Similar mechanisms may be used by other
      depolymerizing enzymes including nucleases, glycosidases, and proteases.

PMID- 7588741
TI  - Temperature-induced changes in fluorescence properties as a probe of porphyrin
      microenvironment in lipid membranes. 2. The partition of hematoporphyrin and
      protoporphyrin in mitochondria.
AB  - The temperature dependence of hematoporphyrin and protoporphyrin fluorescence
      quantum yields (phi F) was studied after delivery to whole mitochondria or
      isolated inner (IMM) and outer (OMM) mitochondrial membranes, obtained from liver
      of Wistar rats. These studies are very sensitive to variations of the porphyrin
      lipid environment. Before incorporation, the porphyrins were dissolved in 0.01 M
      sodium phosphate, 0.15 M NaCl, pH 7.4) NaCl/Pi (only hematoporphyrin) or
      dispersed into liposomes of dipalmitoylphosphoglycerocholine (Pam2GroPCho),
      sometimes enriched with cholesterol or cardiolipin. Whole mitochondria show
      higher incorporation capacity of hematoporphyrin and protoporphyrin than isolated
      IMM and OMM, probably because additional, energy-sensitive transport mechanisms
      for the porphyrin uptake occur in intact organelles. A small decrease in
      protoporphyrin uptake is observed in OMM in comparison with IMM; in contrast, the
      decrease in hematoporphyrin uptake by OMM is rather significant. A comparison
      between the results obtained with IMM, OMM and whole mitochondria show that both
      porphyrins, when released to the intact organelles, preferentially localize in
      the IMM, irrespective of the lipid carrier used. NaCl/Pi-dissolved
      hematoporphyrin probably interacts with some membrane proteins, due to the
      similarity of the Arrhenius plots with those obtained for liposome-entrapped
      human serum albumin/hematoporphyrin complexes which were used as models to mimic
      hematoporphyrin-membrane protein binding sites. Liposomal hematoporphyrin and
      protoporphyrin bind to lipid domains. Hematoporphyrin accumulates in specific,
      localized lipid regions, perhaps in the boundary lipids area surrounding some
      inner-mitochondrial carriers; protoporphyrin accomodates in more rigid, lipid
      areas. On these bases, the higher photoactivity of hematoporphyrin, previously
      observed in mitochondria, in comparison with protoporphyrin, can be easily
      explained. Formation of linear dimers/aggregates, endowed with higher phi F than
      that of the monomers, are postulated to occur for both porphyrins only in the
      inner mitochondrial membrane.

PMID- 7588739
TI  - The structure of the lipid A-core region of the lipopolysaccharides from Vibrio
      cholerae O1 smooth strain 569B (Inaba) and rough mutant strain 95R (Ogawa).
AB  - The lipopolysaccharides (LPS) from Vibrio cholerae 95R, a rough mutant strain of
      O1 V. cholerae 162 (Ogawa), and from smooth O1 V. cholerae 569B (Inaba) were de-O
      acylated. In each case, one part of the products was treated with 48% aqueous HF
      which removed the phosphoryl and fructose residues, then reduced, de-N-acylated,
      and N-acetylated. Another part was de-N-acylated by treatment with hot KOH. The
      products of both degradation pathways were separated by high-performance anion
      exchange chromatography. The major dephosphorylated and defructosylated product 1
      was obtained in pure form, whereas the minor products 2 and 3 were eluted as a
      mixture, as were, from the second degradation, the phosphorylated
      oligosaccharides 4 (major product) and 5 (minor product). No phosphorylated
      component corresponding to oligosaccharide 3 could be identified by NMR
      spectroscopy in the latter mixture. The following structures of oligosaccharides
      1-5 were established on the basis of monosaccharide and methylation analyses,
      Smith degradation, and 1H- and 13C-NMR investigations (correlated, total
      correlated, NOE and heteronuclear correlation spectroscopy; all sugars are
      present as alpha-D-pyranoses except where indicated otherwise; Hep, L-glycero-D
      manno-heptose; Kdo, 3-deoxy-D-manno-2-octulosonic acid). [formula: see text] In
      the untreated lipopolysaccharide, the amino group of the non-reducing terminal
      glucosamine residue is not substituted.

PMID- 7588738
TI  - Binding studies on the combining site of a GalNAc alpha 1-->-specific lectin with
      Thomsen-Friedenreich activity prepared from green marine algae Codium fragile
      subspecies tomentosoides.
AB  - The combining site of a GalNAc alpha 1-->-specific lectin (CFT) with Thomsen
      Friedenreich (T, Gal beta 1-->3-GalNAc alpha 1-->Ser/Thr) activity, purified from
      the subspecies tomentosoides of green marine algae Codium fragile was studied by
      quantitative precipitin and precipitin-inhibition assays. Of 27 glycoforms
      tested, Tn (GalNAc alpha 1-->Ser/Thr) glycoprotein from armadillo submandibular
      glands, and asialo porcine submandibular glycoprotein, which contains T, Tn and
      GalNAc alpha 1-->3Gal(A) sequences, completely precipitated the lectin added, and
      less than 1 microgram glycoprotein was required to precipitate 50% 4.7 micrograms
      lectin nitrogen. However, CFT precipitated negligibly with Pneumococcus type-XIV
      polysaccharide and asialo human alpha 1-acid glycoprotein, that contain
      exclusively the human blood-type-II precursor sequence (II, Gal beta 1-->4GlcNAc)
      at the nonreducing ends. Among the sugar inhibitors tested, the human blood A
      active trisaccharide [Ah, GalNAc alpha 1-->3 (LFuc alpha 1-->2)Gal] was the best
      inhibitor; it was about twice as active as the T disaccharide. Oligosaccharides
      without GalNAc alpha 1--> as part of their sequences were inactive, indicating
      that the acetamido group at C2 of galactose is essential for binding and that
      GalNAc is the main contributor in the T sequence for binding. From the data
      provided, it is clear that the combining site of CFT requires an alpha-anomer of
      GalNAc and recognizes Ah, internal GalNAc alpha 1--> of T and Tn determinants of
      glycans, but not the blood group I/II (Gal beta 1-->3/4GlcNAc) sequences.
      Consequently, CFT is a useful reagent for detecting GalNAc alpha 1-->-containing
      glycoconjugates.

PMID- 7588740
TI  - Temperature-induced changes in fluorescence properties as a probe of porphyrin
      microenvironment in lipid membranes. 1. The partition of hematoporphyrin and
      protoporphyrin in liposomes.
AB  - Temperature-induced fluorescence changes were studied for hematoporphyrin and
      protoporphyrin, incorporated into liposomes of dipalmitoylphosphoglycerocholine
      (Pam2GroPCho) or dimiristoylphosphoglycerocholine (Myr2GroPCho). In some cases,
      cholesterol or cardiolipin were added to the vesicles for better mimicking the
      lipid composition of biological membranes. The experimental conditions were
      appropriately chosen in order to reproduce different possible configurations of
      the porphyrin molecule in lipid membranes: namely, at the polar water/headgroups,
      headgroups/lipid and lipid/lipid interfaces. A peculiar feature observed in some
      of the above liposomal systems was the appearance of discontinuities in the
      Arrhenius plots of the fluorescence quantum yields, with relevant changes of the
      values of activation energies. These discontinuities were due to an increase of
      the fluorescence signal in a temperature range corresponding to the transition of
      the different lipids from the gel-to-liquid crystal state. The observed phenomena
      are consistent with the formation of non-covalent linear dimers or linear higher
      aggregates of the porphyrin molecules. The intermolecular contacts required for
      the formation of these species are favoured by at least three situations:
      disruption of the ordered lipid structure during the gel-to-liquid crystal phase
      transition; competition of other polar groups (e.g., the -OH group of
      cholesterol) with the porphyrin carboxylate groups for the polar phospholipid
      headgroups; and steric constraints due to overcrowding of porphyrin molecules in
      a restricted space.

PMID- 7588742
TI  - Prevention of cholesteryl ester accumulation in P388D1 macrophage-like cells by
      increased cellular vitamin E depends on species of extracellular cholesterol.
      Conventional heterologous non-human cell cultures are poor models of human
      atherosclerotic foam cell formation.
AB  - Since the cellular role of the antioxidative vitamins in the formation of foam
      cells has not yet been studied in detail, we investigated the effect of alpha
      tocopherol and ascorbic acid loading of P388D1 macrophage-like cells on their
      cholesterol and cholesteryl ester levels and their response to the exposure to
      different lipoproteins. alpha-Tocopherol loading, but not ascorbic acid loading,
      of P388D1 cells strongly reduced their cellular cholesteryl ester/cholesterol
      ratio (the crucial indicator of foam cell formation) when fetal calf serum was
      the only extracellular source of cholesterol. Balance studies suggest that this
      effect of alpha-tocopherol was mainly due to a reduced uptake of fetal-calf-serum
      derived cholesterol. alpha-Tocopherol loading, however, did not reduce the
      cholesteryl ester/cholesterol ratio when human unmodified low-density lipoprotein
      (LDL) was added to culture medium containing fetal calf serum. Thus, the uptake
      of fetal-calf-serum-derived cholesterol was competitively reduced by human LDL,
      the uptake of which remained unaffected by alpha-tocopherol. Similarly, alpha
      tocopherol loading did not prevent cholesteryl ester formation induced by human
      LDL either oxidized with Cu2+, ultraviolet light or HOCl, or modified by
      acetylation, aggregation or by malondialdehyde treatment. The present
      experimental conditions lacked any pro-oxidative burden, since (a) ascorbic acid,
      either alone or combined with alpha-tocopherol, did not affect cellular
      cholesteryl ester levels, (b) foam cell formation was not a linear function of
      the degree of oxidative LDL modification, and (c) alpha-tocopherol lacked
      specific effects on oxidatively modified LDL. Thus, the reduction of cellular
      cholesteryl esters by alpha-tocopherol in the absence of human unmodified LDL was
      hardly due to common antioxidative properties of vitamin E. In conclusion, the
      present observation that a desirable alpha-tocopherol effect on the cholesteryl
      ester balance in mouse-tumor-derived P388D1 cells strongly depended on the
      species of extracellular cholesterol carrier, cautions against premature
      generalizations of conventional non-human cell culture data.

PMID- 7588743
TI  - The amino acid sequence and interaction with the nucleosome core DNA of
      transition protein 4 from boar late spermatid nuclei.
AB  - The primary structure of transition protein 4 (TP4) from boar late spermatid
      nuclei was determined by automated Edman degradation of S-pyridylethylated
      protein and of peptides generated by cleavage with Staphylococcus aureus V8
      protease, lysyl endopeptidase and CNBr. Boar TP4 is a basic protein consisting of
      a highly basic amino-terminal half (residues 1-73) and a less basic carboxy
      terminal half (residues 74-138). The latter half includes a highly hydrophobic
      segment, a four-times tandemly repeated sequence, N(G)QNKR(K)X, and a carboxy
      terminal segment containing Trp126. Ultraviolet absorption and CD spectra of TP4
      rat-liver-nucleosome-core-DNA (double-stranded DNA) complexes suggest a TP4
      induced local melting of DNA. Although at 1 mM NaCl TP4 brought about a slight
      stabilization of the DNA against thermal melting, a destabilization of the DNA
      was observed at 50 mM NaCl. From the results of quenching of tryptophan (Trp126)
      fluorescence of TP4 upon its binding to double-stranded and single-stranded boar
      liver nucleosome-core DNA at 50 mM NaCl, the apparent association constants for
      the binding of TP4 to double-stranded and single-stranded DNA were calculated to
      be 7.3 x 10(3) M-1 and 4.1 x 10(3) M-1, respectively. These results suggest that
      TP4, having different domain structures from TP1-3 and a higher affinity for
      double-stranded DNA, induces a local destabilization of DNA probably through the
      stacking of Trp126 with nucleic acid bases.

PMID- 7588744
TI  - Organization of the human N-acetylglucosaminyltransferase V gene.
AB  - UDP-N-acetylglucosamine: alpha-6-D-mannoside beta-1,6-N
      acetylglucosaminyltransferase V (GlcNAc transferase V), which catalyzes the
      transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to alpha-6-D
      mannoside, is an important enzyme regulating the branch formation in complex
      type, N-linked oligosaccharides. It has been reported that the enzymic activity
      of GlcNAc transferase V increases after viral transformation and the enzymic
      product is closely related to the metastasis of tumors. We previously reported
      the purification, cDNA cloning and chromosomal mapping of human GlcNAc
      transferase V. In this study, we describe the isolation of genomic clones
      encoding human GlcNAc transferase V and the structure of the gene. The human
      GlcNAc transferase V gene is divided into 17 exons, and the open reading frame is
      encoded by exons 2-17, spanning 155 kb. Analysis of the 5'-untranslated regions
      of mRNAs from various cells showed multiple sequences depending on the cell
      types. The promoter region of the GlcNAc transferase V gene was characterized by
      searching for any consensus sequences matching those for transcription-factor
      binding. The consensus sequences for a TATA box, AP-1, AP-2, and some other
      transcription factors were found in the 5'-upstream region of exon 1, and
      consensus sequences for LF-A1, HNF1-HP1, liver-restricted transcription factors
      and other factors were also found in intron 1. Chloramphenicol acetyltransferase
      fusion plasmids with either the 5'-upstream region of exon 1 or intron 1 were
      constructed and transfected into COS-1 cells. Promoter activities of both DNA
      fragments were detected, indicating that transcription starts within this region.
      These data suggest that the human GlcNAc transferase V gene employs a multiple
      promoter system for its transcription, and gene expression may therefore be
      regulated in tissue-specific and cell-type-specific manners.

PMID- 7588745
TI  - Isolation of a neuropeptide-degrading endopeptidase from the leech Theromyzon
      tessulatum.
AB  - Extracts of head parts prepared from the leech Theromyzon tessulatum hydrolyse
      the Gly3-Phe4 bond of synthetic [D-Ala2, Leu5]enkephalin and the Gly-His bond of
      benzoyl-Gly-His-Leu. The metabolism of benzoyl-Gly-His-Leu was completely
      inhibited by captopril, consistent with an angiotensin-converting enzyme
      activity. Such an enzyme has recently been isolated from T. tessulatum. However,
      the enkephalin hydrolysis by captopril (100 microM) was inhibited to a maximum of
      70%. The residual activity hydrolyzing enkephalin was inhibited by
      phosphoramidon, consistent with the presence of endopeptidase-24.11, a mammalian
      enzyme implicated in the metabolism of neuropeptides. This enzyme was isolated
      using four steps of purification including gel-permeation and anion-exchange
      chromatographies followed by reverse-phase HPLC. This neuropeptide endopeptidase
      (of approximate molecular mass 45 kDa) hydrolyses, at pH 7 and 37 degrees C, both
      the Gly3-Phe4 bond of synthetic [D-Ala2, Leu5]enkephalin and the Phe8-His9 bond
      of angiotensin I. Cleavage of [D-Ala2, Leu5]enkephalin yields, respectively, the
      Tyr-D-Ala-Gly and Phe-Leu peptides with a specific activity of 29 nmol Tyr-D-Ala
      Gly.min-1.mg protein-1 (Km 95 microM). The hydrolysis of angiotensin I yields
      angiotensin II and the dipeptide His-Leu with a specific activity of 1.2 nmol
      angiotensin min-1.mg protein-1 (Km 330 microM). The metabolism of these peptides
      was totally inhibited by phosphoramidon. This study therefore provides
      biochemical evidence for neuropeptide-degrading endopeptidases in leeches.

PMID- 7588746
TI  - Regulation of rat mast cell protease 1 activity. Protease inhibition is prevented
      by heparin proteoglycan.
AB  - Rat mast cell protease 1 (RMCP-1) is a chymotrypsin-like serine protease
      (chymase) that is specifically expressed by connective-tissue-type mast cells. It
      is stored in the secretory granules of the cells in a complex with heparin
      proteoglycan, and the chymase/heparin proteoglycan complexes are released
      following mast cell activation. The present study was undertaken to examine if
      the association with heparin proteoglycan influenced the regulation of RMCP-1 by
      various macromolecular protease inhibitors. Endogenous mast cell heparin
      proteoglycan was shown to significantly block the inhibition of RMCP-1 by the
      serpins alpha 1-protease inhibitor and alpha 1-antichymotrypsin, as well as the
      inhibition by alpha 2-macroglobulin, soybean trypsin inhibitor and plasma. The
      blocking of protease inhibition showed an optimum at a RMCP-1/proteoglycan ratio
      of 5:1 (by mass), corresponding to approximately 80 RMCP-1 molecules
      bound/proteoglycan molecule. Chymase activity present on intact peritoneal mast
      cells, i.e. present in its native complex with heparin proteoglycan, was also
      shown to be largely resistant to inhibition by alpha 1-antichymotrypsin and alpha
      1-protease inhibitor. Heparin 10-saccharides and 20-saccharides were inefficient
      in preventing the interaction of RMCP-1 with alpha 1-antichymotrypsin, whereas
      pig mucosal heparin (approximately 50 monosaccharide units) blocked protease
      inhibition. We have previously shown that heparin potentiates the catalytic
      activity of RMCP-1 and, in the present study, we show that the mechanism for
      chymase activation involves a sixfold reduction of the Km,app value of RMCP-1 for
      the chromogenic substrate S-2586. Thus, the association of mast cell chymase with
      heparin proteoglycan may serve both to potentiate the catalytic activity of the
      enzyme and to increase the life-span of the chymases by preventing their
      inhibition after exocytosis.

PMID- 7588748
TI  - Association of bile-salt-dependent lipase with membranes of human pancreatic
      microsomes.
AB  - Immunolocalization studies indicated that, in contrast to other enzyme markers of
      human pancreatic secretion, bile-salt-dependent lipase (BSDL) was partly but
      specifically associated with endoplasmic reticulum membranes. In microsomes,
      temperature-induced phase separation using Triton X-114 elucidated the partition
      of BSDL between the aqueous phase and the detergent-rich phase containing
      hydrophilic and membrane proteins, respectively. The size of the membrane
      associated BSDL (approx. 100 kDa) is compatible with that of the fully processed
      enzyme. Fucosylated O- and N-linked oligosaccharide structures were detected by
      means of specific lectins. The membrane-associated BSDL might therefore be
      released from membranes between the trans-Golgi compartment (where terminal
      fucose residues were added) and the zymogen granules where BSDL was mainly found
      in the soluble fraction. Even though BSDL associated with membranes was
      enzymically active, it appeared less efficient than the soluble form. The
      association of BSDL with membranes was pH-dependent and optimal association
      occurred between pH 5-6. The membrane-associated BSDL was released by KBr which
      suggests that the association of BSDL with microsomal membranes involves ionic
      interactions. Lipid-protein interactions are probably not involved in this
      association as BSDL did not associate with liver microsome membranes. We
      attempted to characterize the putative ligand and showed that BSDL and a 94-kDa
      protein, immunologically related to a glucose-regulated protein of 94 kDa
      (Grp94), were co-immunoprecipitated by specific antibodies directed against each
      individual species. It is suggested that the biogenesis of the human pancreatic
      BSDL involves an association with intracellular membranes and that its folding
      may be assisted by molecular chaperones.

PMID- 7588747
TI  - Regulation of mitochondrial biogenesis in Saccharomyces cerevisiae. Intricate
      interplay between general and specific transcription factors in the promoter of
      the QCR8 gene.
AB  - Transcription of the QCR8 gene, encoding subunit VIII of the Saccharomyces
      cerevisiae mitochondrial ubiquinol-cytochrome c oxidoreductase (QCR), is
      controlled by the carbon-source-dependent heme-activator protein complex HAP2/3/4
      and the general transcriptional regulators autonomous replication-site-binding
      factor ABF1 and centromere-binding and promoter-binding factor CPF1. In this
      study, we investigate and dissect the relative contributions and mutual
      interactions of these regulators in transcriptional control. Transcription was
      analyzed both under steady-state conditions and during nutritional shifts, in hap
      delta mutants and after site-specific mutagenesis of the various binding sites in
      the chromosomal context of the QCR8 gene. We present evidence for both direct and
      indirect interactions between ABF1 and HAP2/3/4, and show that HAP2/3/4 is
      essential for a rapid transcriptional induction during transition from repressed
      to derepressed conditions. However, the activator is not the only determinant for
      carbon-source-dependent regulation, and we observe a functional difference
      between HAP2/3/4 and the HAP2/3 subcomplex. ABF1 is required for maintainance of
      basal repressed and derepressed transcription in the steady state of growth. The
      repressive action of the negative modulator CPF1 during escape from glucose
      repression is overcome through the cooperative action of ABF1 and HAP2/3/4. The
      implications of the intricate interactions of these DNA-binding regulators for
      control of expression of mitochondrial protein genes are discussed.

PMID- 7588749
TI  - Chromosomal localisation, inducibility, tissue-specific expression and strain
      differences in three murine peroxisome-proliferator-activated-receptor genes.
AB  - Three murine peroxisome-proliferator-activated-receptor (PPAR) genes were
      localised to chromosome 15 (PPAR alpha), chromosome 17 (PPAR beta) and chromosome
      6 (PPAR gamma). The expression of the three PPAR RNAs was determined using a
      specific RNase protection assay. In liver RNA, PPAR alpha was expressed at the
      highest level, with 20-fold lower levels of PPAR beta, and very low levels of
      PPAR gamma. The three PPAR RNAs showed no sex-specific differences in expression,
      and the levels of these transcripts were unaffected by treatment of mice with
      testosterone or the potent peroxisome proliferator, methylclofenapate. In
      agreement with this data, the level of PPAR alpha protein in liver was unchanged
      after treatment of mice with methylclofenapate. Investigation of the tissue
      specific distribution revealed that the PPAR alpha RNA was expressed at highest
      levels in liver, to moderate levels in kidney and brown adipose tissue, and at
      low levels elsewhere. PPAR beta was expressed at moderate levels in liver, and
      lower levels in other tissues, including brown adipose tissue. In contrast, PPAR
      gamma RNA was expressed at low levels in liver or epididymal white adipose tissue
      and at very low levels elsewhere, but was expressed at high levels in brown
      adipose tissue. The tissue distribution of these receptors suggests an important
      role in lipid metabolism and toxicity for individual members of the PPAR family.
      The expression of PPAR alpha and PPAR beta RNAs was examined in 13 strains of
      mice, and the levels of expression varied within a fourfold range. Polymorphism
      in the size of PPAR alpha RNA from Swiss-Webster mice was detected, and shown to
      be due to a 2-bp mutation in the 3' non-coding region of PPAR alpha in Swiss
      Webster mice.

PMID- 7588750
TI  - Dimeric 3-phosphoglycerate kinases from hyperthermophilic Archaea. Cloning,
      sequencing and expression of the 3-phosphoglycerate kinase gene of Pyrococcus
      woesei in Escherichia coli and characterization of the protein. Structural and
      functional comparison with the 3-phosphoglycerate kinase of Methanothermus
      fervidus.
AB  - The gene coding for the 3-phosphoglycerate kinase (EC 2.7.2.3) of Pyrococcus
      woesei was cloned and sequenced. The gene sequence comprises 1230 bp coding for a
      polypeptide with the theoretical M(r) of 46,195. The deduced protein sequence
      exhibits a high similarity (46.1% and 46.6% identity) to the other known archaeal
      3-phosphoglycerate kinases of Methanobacterium bryantii and Methanothermus
      fervidus [Fabry, S., Heppner, P., Dietmaier, W. & Hensel, R. (1990) Gene 91, 19
      25]. By comparing the 3-phosphoglycerate kinase sequences of the mesophilic and
      the two thermophilic Archaea, trends in thermoadaptation were confirmed that
      could be deduced from comparisons of glyceraldehyde-3-phosphate dehydrogenase
      sequences from the same organisms [Zwickl, P., Fabry, S., Bogedain, C., Haas, A.
      & Hensel, R. (1990) J. Bacteriol. 172, 4329-4338]. With increasing temperature
      the average hydrophobicity and the portion of aromatic residues increases,
      whereas the chain flexibility as well as the content in chemically labile
      residues (Asn, Cys) decreases. To study the phenotypic properties of the 3
      phosphoglycerate kinases from thermophilic Archaea in more detail, the 3
      phosphoglycerate kinase genes from P. woesei and M. fervidus were expressed in
      Escherichia coli. Comparisons of kinetic and molecular properties of the enzymes
      from the original organisms and from E. coli indicate that the proteins expressed
      in the mesophilic host are folded correctly. Besides their higher thermostability
      according to their origin from hyperthermophilic organisms, both enzymes differ
      from their bacterial and eucaryotic homologues mainly in two respects. (a) The 3
      phosphoglycerate kinases from P. woesei and M. fervidus are homomeric dimers in
      their native state contrary to all other known 3-phosphoglycerate kinases, which
      are monomers including the enzyme from the mesophilic Archaeum M. bryantii. (b)
      Monovalent cations are essential for the activity of both archaeal enzymes with
      K+ being significantly more efficient than Na+. For the P. woesei enzyme, non
      cooperative K+ binding with an apparent Kd (K+) of 88 mM could be determined by
      kinetic analysis, whereas for the M. fervidus 3-phosphoglycerate kinase the K+
      binding is rather complex: from the fitting of the saturation data, non
      cooperative binding sites with low selectivity for K+ and Na+ (apparent Kd = 270
      mM) and at least three cooperative and highly specific K+ binding sites/subunit
      are deduced. At the optimum growth temperature of P. woesei (100 degrees C) and
      M. fervidus (83 degrees C), the 3-phosphoglycerate kinases show half-lives of
      inactivation of only 28 min and 44 min, respectively.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7588751
TI  - A cluster of structural and regulatory genes for light-induced carotenogenesis in
      Myxococcus xanthus.
AB  - In the bacterium Myxococcus xanthus, several genes for carotenoid synthesis lie
      together at the carA-carB chromosomal locus and are co-ordinately activated by
      blue light. A 12-kb DNA stretch from wild-type M. xanthus has been sequenced that
      includes the entire carA-carB gene cluster. According to sequence analysis, the
      cluster contains 11 different genes. Intergenic distances are very short or nil
      (implying translational coupling), giving further support to previous evidence
      indicating that most (or all) of the genes in the cluster form a single operon.
      At the promoter region, a potential -35 site for the binding of sigma factors is
      found. However, the -10 region shows little similarity with analogous sites in
      other bacterial promoters. Five (possibly six) genes in the carA-carB operon code
      for enzymes acting on early or late steps of the pathway for carotenoid
      synthesis. Other genes in the operon show no overall similarity with previously
      known genes. However, peptide stretches in the predicted products of two genes
      exhibit strong similarity with the DNA binding domain of the MerR family of
      transcriptional regulators. At least one of the predicted DNA-binding domains is
      altered in a mutant strain affected in light-regulation of the car genes.

PMID- 7588752
TI  - Molecular cloning, functional expression in Escherichia coli, and
      characterization of multiple mitogen-activated-protein kinases from tobacco.
AB  - A screening of four tobacco cDNA libraries by PCR, using degenerate
      oligonucleotides corresponding to motifs conserved in mitogen-activated-protein
      kinases from animals and yeasts, resulted in the isolation of five different PCR
      fragments that showed high sequence similarity to mitogen-activated-protein
      kinases from other organisms. Full-length cDNAs were obtained for two of these,
      ntf4 and ntf6, and we have previously reported the isolation of one of the other
      cDNAs, ntf3 [Wilson, C., Eller, N., Gartner, A., Vicente, O. & Heberle-Bors, E.
      (1993) Plant Mol. Biol. 23, 543-551]. The three cDNAs, ntf3, ntf4 and ntf6, as
      well as a mutated form of ntf3, were fused to the glutathione-S-transferase gene
      and expressed as fusion proteins in Escherichia coli. All three wild-type
      recombinant proteins, with or without the glutathione-S-transferase fragment, are
      capable of autophosphorylation and phosphorylate myelin basic protein, in a
      reaction that is more strongly supported by Mn2+ than by Mg2+, while the kinase
      negative Ntf3 mutant did not show any activity. Western-blot analysis showed that
      the recombinant proteins autophosphorylate on tyrosine residues and are
      recognized by antibodies prepared against mammalian mitogen-activated-protein
      kinases.

PMID- 7588756
TI  - Valyl-tRNA synthetase from Artemia. Purification and association with elongation
      factor 1.
AB  - Two components of the protein biosynthetic machinery, valyl-transfer RNA
      synthetase (VRS) and elongation factor 1 (EF-1), have been isolated as a complex
      from several mammalian tissues. However, yeast VRS, which lacks an amino-terminal
      extension, does not associated with EF-1. We purified VRS from the brine shrimp
      Artemia and investigated its interaction with EF-1. Western blotting of crude
      Artemia extracts revealed the presence of two forms of VRS, differing in size and
      capacity to associate with EF-1. About 80% of the total VRS corresponds to a
      polypeptide of 130 kDa which behaves as a monomer upon gel filtration. Only the
      larger form of 140 kDa coelutes, cosediments and co-immunoprecipitates with the
      EF-1 alpha 2 beta gamma delta complex. The ratio of the two forms of VRS remains
      constant throughout early development. The possible origin and mode of expression
      of the two forms of VRS present in Artemia are discussed.

PMID- 7588753
TI  - Molecular cloning of the cDNA encoding human skeletal muscle triadin and its
      localisation to chromosome 6q22-6q23.
AB  - We have cloned and sequenced the cDNA encoding triadin, a junctional terminal
      cisternae protein from human skeletal muscle. The cDNA, 2941 base pairs in
      length, encodes a protein of 729 amino acids with a predicted molecular mass of
      81,545 Da. Hydropathy analysis indicates that triadin of human skeletal muscle
      has the same topology in the myoplasmic, transmembrane and sarcoplasmic reticulum
      luminal domains as that of triadin from rabbit skeletal muscle. The number and
      relative position of potential modulation sites are also conserved between the
      human and rabbit proteins. The cDNA sequence of the predicted sarcoplasmic
      reticulum luminal domain of human triadin diverged from that of rabbit, with an
      observed similarity of 82%, translating to an identity of 77% in amino acid
      sequence. Two insertions of 9 and 12 residues in the amino acid sequence were
      observed in the predicted luminal domain of triadin, although the structural and
      functional consequences of such insertions are expected to be minimal. Using
      fluorescence in situ hybridisation, we have assigned the gene encoding human
      triadin to the long arm of chromosome 6 in the region 6q22-6q23. Our structural
      analysis of human triadin supports a central role for this protein in the
      mechanism of skeletal muscle excitation/contraction coupling.

PMID- 7588754
TI  - Molecular biological analysis of a bidirectional hydrogenase from cyanobacteria.
AB  - An 8.9-kb segment with hydrogenase genes from the cyanobacterium Anabaena
      variabilis has been cloned and sequenced. The sequences show homology to the
      methyl-viologen-reducing hydrogenases from archaebacteria and, even more
      striking, to the NAD(+)-reducing enzymes from Alcaligenes eutrophus and Nocardia
      opaca as well as to the NADP(+)-dependent protein from Desulfovibrio
      fructosovorans. The cluster from A. variabilis contains genes coding for both the
      hydrogenase heterodimer (hoxH and hoxY) and for the diaphorase moiety (hoxU and
      hoxF) described for the A. eutrophus enzyme. In A. variabilis the gene cluster is
      split by two open reading frames (between hoxY and hoxH and between hoxU and
      hoxY, respectively), and a probably non-coding 0.9-kb segment in an unusual way.
      The hoxH partial sequence from Anabaena 7119 and Anacystis nidulans was amplified
      by PCR. Using the labeled segment from A. 7119 as probe, Southern analysis
      revealed homologous gene segments in the cyanobacteria A. 7119, Anabaena
      cylindrica, Anacystis nidulans and A. variabilis. The bidirectional hydrogenase
      from A. nidulans was purified and digests were sequenced. The amino acid
      sequences obtained showed partial identities to the amino acid sequences deduced
      from the DNA data of the 8.9-kb segment from A. variabilis. Therefore the 8.9-kb
      segment contains the genes coding for the bidirectional, reversible hydrogenase
      from cyanobacteria. Crude extracts from A. nidulans perform NAD(P)H-dependent H2
      evolution corroborating the molecular biological demonstration of the NAD(P)(+)
      dependent hydrogenase in cyanobacteria.

PMID- 7588755
TI  - Site-directed mutagenesis and sugar-binding properties of the wheat germ
      agglutinin mutants Tyr73Phe and Phe116Tyr.
AB  - Wheat germ agglutinin is a dimeric lectin composed of two identical subunits.
      Each subunit consists of four homologous hevein-like domains of 42 or 43 amino
      acids each. Amino acid residues at the same position in each domain involved in
      sugar binding are thought to play a similar role in sugar binding. In order to
      clarify the role of the amino acid residue at domain position 30 of wheat germ
      agglutinin isolectin 2 (WGA2) in sugar binding, two WGA2 variants each containing
      a mutation, either Tyr73-->Phe (domain B) or Phe116-->Tyr (domain C), were
      produced. The binding activity for (GlcNAc)3 and the three-dimensional structure
      of these mutants were characterized by comparing with the properties of wild-type
      WGA2. Equilibrium dialysis experiments using (GlcNAc)3 indicated that the
      mutation Tyr73-->Phe reduced the overall sugar-binding activity at both pH 5.9
      and pH 4.7. In addition, positive cooperativity toward (GlcNAc)3 binding was
      observed at pH 4.7. In contrast, the mutation of Phe116-->Tyr increased the
      overall sugar-binding activity at pH 5.9, but reduced this activity at pH 4.7
      without changing the number of sugar-binding sites. Positive cooperativity was
      not observed at pH 5.9 or pH 4.7. X-ray crystallographic analysis of mutant WGA2
      revealed that the mutation of Tyr73-->Phe caused a side chain movement of the
      Glu115 residue of the opposite subunit that formed a hydrogen bond with Tyr73 in
      wild-type WGA2. No changes were observed in the backbone structure and the
      disposition of the benzene ring of Phe73. The mutation Phe116-->Tyr caused the
      formation of a new hydrogen bond between Tyr116 and Glu72 of the opposite
      subunit. The changes in the sugar-binding properties in WGA2 mutants are
      discussed in relation to the structural change at the binding site.

PMID- 7588757
TI  - Interactions responsible for the pH dependence of the beta-hairpin conformational
      population formed by a designed linear peptide.
AB  - In a previous work [Blanco, F.J., Jimenez, M.A., Herranz, J., Rico, M., Santoro,
      J. & Nieto, J. L. (1993) J. Am. Chem. Soc. 115, 5887-5888] we showed that a
      short, designed linear peptide, YQNPDGSQA (peptide 1), can form a monomeric beta
      hairpin in aqueous solution. The pH dependence of the beta-hairpin conformation
      formed by the designed peptide and a series of related peptides has been examined
      in this work using 1H-NMR methods. Three pH-dependent interactions have been
      identified: a local interaction, unimportant structurally, between the C-terminal
      carboxylate group and the side-chain amide group of Q8; an electrostatic
      interaction between the main-chain N-terminus and C-terminus; and a hydrogen bond
      involving the side-chain amide protons of N3 and the side-chain carboxylate group
      of D5. The latter two interactions are particularly relevant as they increase the
      population of the beta-hairpin conformation. We also observe in the mutant
      peptide A9H that the interaction between Y1 and H9 (of the type proposed to exist
      in proteins) does not contribute to beta-hairpin stabilisation in our peptide
      system. Peptide 1 is, therefore, a very suitable model to examine the different
      interactions that contribute to beta-hairpin stability.

PMID- 7588759
TI  - Mutations at positions 11 and 60 of insulin-like growth factor 1 reveal
      differences between its interactions with the type I insulin-like-growth-factor
      receptor and the insulin receptor.
AB  - Insulin-like growth factor 1 (IGF-1) and three analogues ([V11I]IGF-1, [V11T]IGF
      1, and [Y60F]IGF-1), constructed by site-directed mutagenesis, were expressed as
      fusion proteins and secreted into the periplasmic space of Escherichia coli.
      Purified IGF were obtained following IgG Sepharose affinity and cation-exchange
      chromatographies of the products of hydroxylamine cleavage of fusion proteins.
      The properties of the mutants were assessed using (a) quantification of
      affinities for the human insulin receptor overexpressed on NIH 3T3 cells, (b)
      quantification of affinities for the type I IGF receptor via competition for
      binding to a monolayer of MDA-MB-231 cells, (c) promotion of the in vitro
      mitogenesis of growth-arrested MCF-7 cells in the presence of 17-beta-oestradiol,
      and (d) a competition assay for binding to IGF-binding proteins secreted by MCF-7
      cells. The mutants exhibited decreases in affinity for the insulin receptor,
      relative to IGF-1, of 2.6-, 3.8- and, 8.8-fold for [Y60F]IGF-1, [V11I]IGF-1, and
      [V11T]IGF-1, respectively. IGF-1, [V11I]IGF-1, and [Y60F]IGF-1 were of equal
      potency in the growth assay and in affinity for the type I IGF receptor.
      [V11T]IGF-1 exhibited a three fold loss of potency in the type I IGF receptor
      binding and growth assays. The mutants did not differ significantly from IGF-1 in
      their affinities for the IGF-binding proteins. The full-activity of [Y60F]IGF-1
      at the type I IGF receptor, in contrast to the weakened receptor affinity of IGF
      1 with a Leu substitution at this position, indicates a requirement for an
      aromatic ring, rather than a hydroxyl group, in the interaction of IGF-1 with the
      type I IGF receptor. The decrease in affinity for the insulin receptor of all the
      mutants indicates that, as in insulin, the residues Val11 and Tyr60 are important
      for the interaction of IGF-1 with the insulin receptor. The unchanged or minor
      changes in the affinities of the mutants for the type I IGF receptor contrast
      with the more deleterious effects of the mutations on insulin receptor binding
      and with the properties of analogues of insulin mutated at equivalent sites: 3
      fold and 5-10-fold reductions in biological activity for [VB12I]insulin and
      [YA19F]insulin, respectively. Thus, the results obtained using the mutants
      indicate important differences between the IGF-1/type I IGF receptor and
      insulin/insulin receptor interactions.

PMID- 7588758
TI  - Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease.
AB  - One of the principle peptide components of the amyloid plaque deposits of
      Alzheimer's disease in humans is the 40-amino-acid peptide beta-amyloid A4-(1-40)
      peptide. The full-length A4-(1-40)-peptide was chemically synthesized and the
      solution structure determined by two-dimensional nuclear magnetic resonance
      spectroscopy and restrained molecular-dynamics calculations. Synthetic human A4
      (1-40)-peptide was soluble and non-aggregating for several days in 40% (by vol.)
      trifluoroethanol/water. All spin systems could be unambiguously assigned, and a
      total of 203 sequential and medium-range cross-peaks were found in the NOESY
      (nuclear Overhauser enhancement spectroscopy) spectrum. Long-range NOE cross
      peaks that would indicate tertiary structure of the peptide were absent. The main
      secondary-structure elements found by chemical-shift analysis, sequential and
      medium-range NOESY data, and NOE-based restrained molecular-dynamics calculations
      were two helices, Gln15-Asp23 and Ile31-Met35, whereas the rest of the peptide
      was in random-coil conformation. A similar secondary structure is suggested for
      the aggregation part of prions, the postulated causative agents of the
      transmissible spongiform encephalopathy. The sequence of the helical part of
      prion proteins was observed to be remarkably similar to the sequence of the
      helical part of human A4-(1-40)-peptide.

PMID- 7588760
TI  - The Fusobacterium nucleatum major outer-membrane protein (FomA) forms trimeric,
      water-filled channels in lipid bilayer membranes.
AB  - The pore-forming activity of the major outer-membrane protein FomA of the
      anaerobic Fusobacterium nucleatum was studied in artificial lipid bilayer
      membranes. FomA was isolated from F. nucleatum strains Fev1, ATCC 10953, and ATCC
      25586 by extraction with lithium dodecyl sulfate and lithium chloride and had an
      apparent molecular mass of about 40 kDa. When solubilized at low temperatures,
      the protein ran with an apparent molecular mass of about 62 kDa on SDS/PAGE.
      Cross-linking experiments and two-dimensional SDS/PAGE gave evidence that the 62
      kDa protein band represented the trimeric form of FomA. The protein trimers were
      susceptible to SDS and temperature. The stability of the porin trimers varied
      among the strains. The properties of the FomA channels were studied in
      reconstitution experiments with black lipid bilayer membranes. The F. nucleatum
      porins formed channels with single-channel conductances in the range 0.66-1.30 nS
      in M KCl. The single-channel conductance was a function of the mobilities of the
      ions present in the aqueous solution bathing the bilayer membrane. This means
      that FomA forms general diffusion channels since (a) the conductance showed a
      linear dependence on the salt concentration, (b) the ion selectivity was small
      and varied for the three strains, and (c) the channels did not exhibit any
      binding site for maltotriose or triglycine. The water-filled channel was voltage
      dependent, and conductance decrements were observed at transmembrane potentials
      of +/- 50 mV. The conductance decrement steps were about one-third of the total
      conductance of a functional unit in its fully 'open' state. This strongly
      suggests that the trimer is the functional unit of the porin.

PMID- 7588763
TI  - Cyclic voltammetry and 1H-NMR of Rhodopseudomonas palustris cytochrome c2.
      Probing surface charges through anion-binding studies.
AB  - The effects of increasing concentrations of Cl-, ClO4-, and HCO3- on the redox
      potential of Rhodopseudomonas palustris cytochrome c2 indicate that the two
      polyatomic anions bind specifically to the protein at one site, while chloride
      simply exerts an ionic atmosphere effect. The change in E degree upon specific
      anion binding allows us to probe for the influence of surface charges on the
      redox potential of cytochromes c. The decrease in redox potential at null ionic
      strength (delta E degree I = 0) due to anion neutralization of one positive
      surface charge was found to be 23 mV with perchlorate and 33 mV with bicarbonate.
      These values compare reasonably well with previous theoretical predictions and
      estimates of the effect of charge alteration on the E degree values in
      cytochromes c chemically modified or mutated at surface lysines. These delta E
      degree values, determined on the unmodified protein, are unprecedented for c-type
      cytochromes. The anion-induced chemical shift changes of the hyperfine-shifted
      heme 1H-NMR resonances of the oxidized protein yield lower limit values of 53 M-1
      and 18 M-1 for the affinity constant for specific HCO3- and ClO4- binding,
      respectively.

PMID- 7588764
TI  - Two soluble forms of glutamate dehydrogenase isoproteins from bovine brain.
AB  - Two soluble forms of novel glutamate dehydrogenase isoproteins, designated GDH I
      and GDH II, have been purified from bovine brain. GDH I and GDH II were separated
      on a hydroxyapatite column and eluted by a step gradient at different phosphate
      concentrations (30 mM and 50 mM for GDH I and GDH II, respectively). The
      preparations were homogeneous on SDS/PAGE. GDH I and GDH II showed similarity in
      their molecular sizes and are composed of six identical subunits having a
      molecular size of 57,500 Da. Differences between the biochemical properties of
      GDH I and GDH II, such as N-terminal amino acid sequences of intact and tryptic
      digested enzymes, kinetic parameters, optimum pH and heat stability, were
      extensively examined in both reductive amination of alpha-oxoglutarate and
      oxidative deamination of glutamate. The different effects of ADP on GDH
      isoproteins were also studied under various conditions. These results indicate
      that GDH I and GDH II, isolated from bovine brain, are novel and distinct
      polypeptides.

PMID- 7588765
TI  - Reaction mechanism of thioredoxin: 3'-phospho-adenylylsulfate reductase
      investigated by site-directed mutagenesis.
AB  - Properties of purified recombinant adenosine 3'-phosphate 5'-phosphosulfate
      (PAdoPS) reductase from Escherichia coli were investigated. The Michaelis
      constants for reduced thioredoxin and PAdoPS are 23 microM and 10 microM,
      respectively; the enzyme has a Vmax of 94-99 mumol min-1 mg-1 and a molecular
      activity/catalytically active dimer of 95 s-1. Adenosine 3',5'-bisphosphate
      (PAdoP) inhibits competitively (Ki 4 microM) with respect to PAdoPS; adenosine
      2',5'-bisphosphate and sulfite are not inhibitory. Alkylation by SH-group
      inhibitors irreversibly inactivates the enzyme. The structural gene (cysH)
      encodes for a small polypeptide with a single Cys residue located in a conserved
      cluster (KXECGI/LH) of amino acids. Involvement of the only Cys and of Tyr209 in
      the reduction of PAdoPS to sulfite was investigated by site-specific mutagenesis:
      cysH was mutated by single-strand-overlay extension PCR; the mutated genes were
      cloned in pBTac1 and expressed in E. coli RL 22 (delta cysHIJ). Homogenous
      Cys239Ser and Tyr209Phe mutant PAdoPS reductases were investigated for altered
      catalytic properties. Mutation of the single Cys reduced Vmax by a factor of 4.5
      x 10(3) (Vmax = 0.02-0.013 mumol min-1 mg-1) with marginal effects on Km for
      PAdoPS (19 microM) and reduced thioredoxin (14 microM). Mutation of Tyr209
      drastically affected saturation with thioredoxin (Km 1.5 microM) and decreased
      Vmax (0.22-0.25 mumol min-1 mg-1) in addition to a small increase in Km for
      PAdoPS (31 microM). Chromophores as prosthetic groups were absent from
      recombinant PAdoPS reductase. Difference absorption spectra between reduced and
      oxidized forms of wild-type and mutated proteins indicated that, in addition to
      Cys239 and Tyr209, an unidentified Trp (delta lambda max 292 nm) appears to be
      involved in the reduction. The data suggest a special ping-pong mechanism with
      PAdoPS reacting with the reduced enzyme isomer in a Theorell-Chance type
      mechanism.

PMID- 7588761
TI  - Spectroscopic characterisation of an aconitase (AcnA) of Escherichia coli.
AB  - A spectroscopic study of an aconitase, AcnA, from Escherichia coli is presented.
      The amino acid sequence of AcnA has 53% identity with mammalian cytosolic
      aconitase (c-aconitase) which is the translational regulator known as iron
      regulatory factor (IRF). In the [3Fe-4S](+)-containing, inactive state, AcnA
      displays an EPR signal which is not unlike the corresponding signal from
      mammalian mitochondrial aconitase (m-aconitase) but is even more similar to the
      signal from c-aconitase. This is perhaps related to the greater similarity of the
      AcnA amino acid sequence with c-aconitase. Magnetic circular dichroism (MCD)
      spectroscopy has revealed that the electronic structure of the [3Fe-4S] cluster
      of AcnA must be similar to, but not identical to that of m-aconitase. Whilst the
      [Fe-4S] clusters from both of these enzymes display some features in their MCD
      spectra common to [3Fe-4S] clusters in general, their spectra overall are unique
      and indicate that the Fea atom of the [4Fe-4S] form is not the only unusual
      feature of the [Fe-S] clusters of aconitases. Active [4Fe-4S]-containing AcnA can
      be reduced to yield an EPR signal due to a [4Fe-4S]+ cluster which is
      indistinguishable from the signals from the [4Fe-4S]+ cluster in the mammalian
      enzymes. However, in contrast to the mammalian enzymes, the EPR signals of the
      cluster in AcnA are not significantly perturbed upon the addition of substrate.
      Furthermore, the catalytic activity of [Fe-4S](2+)-containing AcnA is fivefold
      higher than that of m-aconitase. The mechanistic implications of these data are
      discussed. A novel S = 1/2 EPR signal with g approximately 2 was observed in AcnA
      upon treatment with EDTA. The species giving rise to this signal is proposed to
      be an intermediate in cluster deconstruction.

PMID- 7588766
TI  - Involvement of N-linked carbohydrate chains of pig zona pellucida in sperm-egg
      binding.
AB  - The sperm receptor activity of pig zona pellucida has been previously shown to
      exist in one of the components, pig zona protein 3 alpha (PZP3 alpha), that can
      be purified after the removal of sialylated and/or sulfated N
      acetylpoly(lactosamine) by digestion with endo-beta-galactosidase. In this study,
      we examined whether N-linked or O-linked carbohydrate chains are involved in the
      sperm receptor activity of pig zona pellucida. The elimination of N-linked
      carbohydrate chains from endo-beta-galactosidase-digested PZP3 alpha by digestion
      with N-glycanase markedly reduced its inhibitory effect on sperm-egg binding in
      an in vitro competition assay, whereas the elimination of O-linked carbohydrate
      chains by alkali treatment hardly reduced the inhibitory effect. These results
      indicate that N-linked carbohydrate chains of PZP3 alpha play a major role in
      mediating the sperm binding of zona pellucida in pig.

PMID- 7588767
TI  - Enzymic and chemical reduction of the iron center of the Escherichia coli
      ribonucleotide reductase protein R2. The role of the C-terminus.
AB  - The active form of protein R2, the small subunit of ribonucleotide reductase,
      contains a diferric center and a free radical localized at Tyr122. Hydroxyurea
      scavenges this radical but leaves the iron center intact. The resulting metR2
      protein is inactive. The introduction of a radical into metR2 is dependent on the
      reduction of the iron center. In Escherichia coli, this is achieved by an enzyme
      system consisting of a NAD(P)H:flavin oxidoreductase and a poorly defined protein
      fraction, fraction b. Assuming that the iron center is deeply buried within the
      protein, electron transfer is suggested to occur over long distances. Site
      directed mutagenesis allowed us to identify two invariant residues, Tyr356 at the
      C-terminal part of the protein and Tyr122 located 0.5 nm away from the closest
      iron atom, as mediators of this electron transfer. We also found that
      deazaflavins were excellent catalysts in the photoreduction of the iron center of
      metR2 and generation of the tyrosyl radical, providing the simplest and most
      efficient model for the physiological flavin reductase/fraction b activating
      system. The properties of the model reaction are described.

PMID- 7588762
TI  - A casein-kinase-2-related protein kinase is tightly associated with the large T
      antigen of simian virus 40.
AB  - The simian virus 40 (SV40) large T antigen is a multifunctional protein involved
      in SV40 cell transformation and lytic virus infection. Some of its activities are
      regulated by interaction with cellular proteins and/or by phosphorylation of T
      antigen by various protein kinases. In this study, we show that immuno-purified T
      antigen from SV40-transformed cells and from baculovirus-infected insect cells is
      tightly associated with a protein kinase that phosphorylates T antigen in vitro.
      In the presence of heparin or a peptide resembling a protein kinase CK2
      recognition site, the phosphorylation of T antigen by the associated kinase is
      reduced whereas a p34cdc2-kinase-specific peptide has no influence. In addition,
      the T-antigen-associated protein kinase can use GTP and ATP as phosphate donors.
      These properties together with the observation that immunopurified T antigen can
      be phosphorylated by the addition of protein kinase CK2 suggest that at least one
      of the T-antigen-associated protein kinases is CK2 or a protein-kinase-CK2
      related enzyme. The association of recombinant CK2 with T antigen was strongly
      confirmed by in vitro binding studies. Experiments with temperature-sensitive
      SV40-transformed cells provide evidence for a close correlation between cell
      transformation and phosphorylation of T antigen by the associated protein kinase.

PMID- 7588768
TI  - Transient and steady-state kinetics of the oxidation of scopoletin by horseradish
      peroxidase compounds I, II and III in the presence of NADH.
AB  - Scopoletin, a naturally occurring fluorescent component of some plants and a
      proven plant growth inhibitor, is a known reactant with peroxidase. However, the
      kinetics of the elementary steps of the reaction have never been investigated,
      nor has the quantitative effect of interfering substances ever been explored in
      detail, despite the fact that scopoletin is widely used in a peroxidase assay for
      H2O2. In this work, we employed both transient-state and steady-state methods to
      determine the second-order rate constants for the oxidation of scopoletin by the
      horseradish peroxidase (HRP) intermediate compounds I and II: (3.7 +/- 0.1) x
      10(6) M-1 s-1 and (8.5 +/- 0.5) x 10(5) M-1 s-1 at 20 degrees C, pH 6.0 and ionic
      strength of 0.1 M. We investigated the possible inhibitory effect of NADH on the
      reaction of scopoletin with HRP and also the effect of scopoletin on the NADH
      reaction. In the presence of NADH the rate constant for the reaction between HRP
      I and scopoletin decreased slightly to (2.8 +/- 0.1) x 10(6) M-1 s-1. Thus,
      although NADH is also a peroxidase substrate, it cannot compete effectively for
      the oxidized forms of the enzyme. On the other hand, scopoletin stimulates the
      oxidation of NADH by the HRP/H2O2 system, apparently by forming a phenoxyl
      radical which then oxidizes NADH to NAD. radicals. We present spectral evidence
      showing that in the aerobic reaction between HRP and NADH at pH 7.0 (without
      exogenously added H2O2) HRP-II is the dominant enzyme intermediate with HRP-III
      also detectable. Addition of scopoletin to the HRP/NADH system leads to a
      biphasic reaction in which HRP-II and HRP-III disappear. The rate constants for
      both phases are linearly dependent on scopoletin concentration. We attribute the
      faster phase to the HRP-II reaction with scopoletin with a rate constant of (6.2
      +/- 0.1) x 10(5) M-1 s-1 and the slower phase to the HRP-III reaction with
      scopoletin with rate constant (5.0 +/- 0.4) x 10(4) M-1 s-1. Our present work not
      only provides rate constants for the oxidation of scopoletin by HRP-I, II and III
      but also elucidates the interactions that possibly occur physiologically during
      NADH oxidation in the presence of scopoletin.

PMID- 7588769
TI  - Hydrogen isotope effects in the reactions catalyzed by H2-forming N5,N10
      methylenetetrahydromethanopterin dehydrogenase from methanogenic Archaea.
AB  - H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase from
      methanogenic Archaea, which is a novel hydrogenase containing neither nickel nor
      iron-sulfur clusters, catalyzes the reversible reduction of N5,N10
      methenyltetrahydomethanopterin (CH identical to H4MPT+) with H2 to N5,N10
      methylenetetrahydromethanopterin (CH2 = H4MPT) and a proton (delta G degree' = 
      5.5 kJ/mol). The enzyme also catalyzes a CH identical to H4MPT(+)-dependent H2/H+
      exchange. We report here on kinetic deuterium isotope effects in these reactions.
      When CH identical to H4MPT+ reduction was performed with D2 instead of H2, Vmax
      and the Km did not change. A primary isotope effect of 1 was found at all pH and
      temperatures tested and independent of whether H2O or D2O was the solvent. The
      findings indicate that a step other than the activation of H2 was rate
      determining in CH identical to H4MPT+ reduction with H2. This was substantiated
      by the observation that also the CH identical to H4MPT(+)-dependent H2/H+
      exchange reaction did not exhibit an appreciable deuterium isotope effect. Vmax
      for CH2 = H4MPT dehydrogenation to CH identical to H4MPT+ and H2 was only 2-3
      times higher than for CD2 = H4MPT dehydrogenation to CD identical to H4MPT+ and
      HD. Such a small primary isotope effect indicates that the breakage of the C-H
      bond in the methylene group of CH2 = H4MPT was only rate-limiting when hydrogen
      was substituted by a deuterium.

PMID- 7588770
TI  - Structural elucidation of novel methylglucose-containing polysaccharides from
      Mycobacterium xenopi.
AB  - The structures of methylglucose-containing polysaccharides (MeGlc PS) from
      Mycobacterium xenopi were investigated using high-pH anion-exchange
      chromatography and liquid secondary-ion mass spectrometry. We report the
      structure of two novel MeGlc PS, referred to as A and B. MeGlc PS A is composed
      of 16 D-glucopyranose residues, 11 of which are methylated, and MeGlc PS B
      contains 15 D-glucopyranose residues, 10 of which are methylated. The main
      structural feature of both MeGlc PS A and B, compared to the previously described
      structures, is the absence of the tetrasaccharide non-reducing end 3-O-Me-D-Glcp
      [alpha(1-->4)-D-Glcp]3. The MeGlc PS A structure is similar to the synthetic
      polysaccharide [Saier, M. H. & Ballou, C. E. (1968) J. Biol. Chem. 243, 992
      1005], having a lower affinity for fatty acids than the MeGlc PS of Mycobacterium
      smegmatis [Kiho, T. & Ballou, C. E. (1988) Biochemistry 27, 5824-5828]. Thus, the
      occurrence of MeGlc PS A and the consequences on the regulation of fatty acid
      synthetase I activity involved in the biosynthesis of fatty acids, precursors of
      mycolic acid biosynthesis, is discussed.

PMID- 7588771
TI  - Compositional analysis of glucosaminyl(acyl)phosphatidylinositol accumulated in
      HeLa S3 cells.
AB  - GlcN(acyl)PtdIns, a derivative of phosphatidylinositol (PtdIns) in which
      glucosamine and a fatty acid are linked to inositol hydroxyl groups, has been
      proposed to be an intermediate in the mammalian biosynthetic pathway for
      glycosylphosphatidylinositol (glycosyl-PtdIns) anchors of membrane proteins. In
      this report, GlcN(acyl)PtdIns metabolically labeled with [3H]inositol is shown to
      accumulate in a HeLa S3 cell subline. The amount of GlcN(acyl)PtdIns in these
      HeLa S3 cells is about 10(7) molecules/cell, a level comparable to those of the
      most abundant glycosyl-PtdIns-containing molecules reported to date.
      GlcN(acyl)PtdIns was purified by a two-step procedure involving octyl-Sepharose
      and thin-layer chromatography. Octyl-Sepharose separated phospholipids according
      to their number of hydrocarbon chains: one in 2-lysoPtdIns, two in PtdIns, and
      three in GlcN(acyl)PtdIns. Purification also was aided by prior treatment of
      lipid extracts with bee venom phospholipase A2, an enzyme that did not cleave
      GlcN(acyl)PtdIns. The GlcN-inositol head group in purified GlcN(acyl)PtdIns was
      confirmed by a number of procedures, including cation-exchange chromatography and
      mass spectrometry; after radiomethylation, an equal molar ratio of
      GlcN(Me)2/inositol was measured. Fatty acid analysis indicated an overall
      stoichiometry of 2.3 mol fatty acid/mol inositol with palmitic (16:0), stearic
      (18:0) and oleic (18:1) acids being predominant. Analysis of GlcN(acyl)inositol
      produced by HF fragmentation showed that palmitate was the acyl group attached to
      inositol and indicated that stearic and oleic acids were in the glycerolipid.
      Base methanolysis revealed that about 15% of the purified GlcN(acyl)PtdIns
      contained alkylglycerol. A substantial conversion of GlcN(acyl)PtdIns to a
      slightly more polar lipid occurred after overnight incubation in even mildly
      alkaline buffers. Although the current data do not allow proposal of a structure
      for this lipid, its formation from GlcN(acyl)PtdIns may be important because the
      conversion appeared to occur in vivo.

PMID- 7588772
TI  - Immunoassay for the quantification of intracellular multi-ubiquitin chains.
AB  - A sandwich ELISA has been developed to measure intracellular levels of multi
      ubiquitin chains. The mixture of multi-ubiquitin chains, prepared in vitro by
      incubation of ubiquitin (plus 125I-ubiquitin) and lysozyme with ubiquitin
      ligating enzymes and ATP, was partially purified and established as a standard
      named the multi-ubiquitin-chain reference preparation 1 (MUCRP1). The
      concentration of MUCRP1 was calculated from the recovered radioactivity of 125I
      ubiquitin. All measurements by the ELISA were expressed in terms of MUCRP1. The
      ELISA showed good sensitivity (98 pg/ml), precision (intra-assays < 6%) and
      reproducibility (interassay < 9%). In addition, there was no substantial cross
      reaction with mono-, di- and tri-ubiquitin, or mono-ubiquitinated and di
      ubiquitinated lysozyme in the ELISA, and large multi-ubiquitin chains (n >
      approximately 6) may be fully reactive. These results combined with excellent
      results in the recovery and dilution tests guarantee accurate measurement of
      multi-ubiquitin chains in cell extracts prepared with a lysis buffer (water
      soluble) or the buffer supplemented 8 M urea (urea soluble). The level of the
      water-soluble multi-ubiquitin chains in reticulocytes was lower than that of
      erythrocytes, but the urea-soluble chain level was higher in the reticulocytes.
      Heat-shock treatment of HeLa cells increased the urea-soluble multi-ubiquitin
      chains. These data indicate that this ELISA provides a useful and reliable
      approach to the study of intracellular multi-ubiquitin-conjugate turnover.

PMID- 7588773
TI  - Binding of human prothymosin alpha to the leucine-motif/activation domains of
      HTLV-I Rex and HIV-1 Rev.
AB  - Rex of human T-cell leukemia virus type I (HTLV-I) and Rev of human
      immunodeficiency virus 1 (HIV-1) are post-transcriptional regulators of viral
      gene expression. By means of affinity chromatography, we purified an 18-kDa
      cellular protein that bound to the conserved leucine-motif/activation domain of
      HTLV-I Rex or HIV-1 Rev. The protein that was purified through a Rev-affinity
      column was found to bind to Rex immunoprecipitated with anti-Rex IgG from an HTLV
      I-producing cell line. We analyzed the purified approximately 18-kDa protein
      biochemically and identified it as prothymosin alpha. The binding activity of
      prothymosin alpha to Rev or Rex was completely abolished when the epsilon-amino
      groups of its lysine residues were chemically modified by N-succinimidyl-3-(4
      hydroxy-3,5-diodo- phenyl)propionate. The functional relationship between the
      nuclear protein prothymosin alpha and Rex-Rev is discussed.

PMID- 7588774
TI  - An alternative role for the src-homology-domain-containing phosphotyrosine
      phosphatase (SH-PTP2) in regulating epidermal-growth-factor-dependent cell
      growth.
AB  - The association of the src homology 2 (SH2) domain-containing tyrosine
      phosphatase (SH-PTP2) with the activated epidermal growth factor (EGF) and
      platelet-derived growth factor receptors, as well as the insulin receptor
      substrate 1 and growth-factor-receptor-bound protein 2 and its intrinsic tyrosine
      phosphatase activity suggests an important role for this phosphatase in signal
      transduction. Previous studies have shown a positive role for SH-PTP2 in growth
      factor-mediated cell signaling. We show here that SH-PTP2 can also function to
      negatively regulate EGF-mediated signal transduction in the human glioma cell
      line SNB19. We demonstrate this by showing that, in SNB19 cells, which lack the
      ability to proliferate in response to EGF but retain the ability to bind EGF and
      also activate the EGF receptor as well as allow for the association of SH-PTP2
      with the phosphorylated receptor, stable overexpression of an interfering SH-PTP2
      mutant can restore the ability of these cells to proliferate in response to EGF.

PMID- 7588775
TI  - Molecular cloning of CTP:phosphocholine cytidylyltransferase from Plasmodium
      falciparum.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) is the rate-limiting and regulatory
      enzyme in the synthesis of phosphatidylcholine, the major membrane phospholipid,
      in Plasmodium. The structural gene encoding CCT was isolated from the human
      malaria parasite Plasmodium falciparum. This was achieved using the PCR to
      amplify genomic DNA with degenerate primers constructed on the basis of conserved
      regions identified within yeast and rat liver CCT molecules, and using the PCR
      product to screen a genomic library. The P. falciparum CCT gene encodes a protein
      of 370 amino acids (42. 6 kDa) and displays 41-43% similarity (28-29% identity)
      to CCT molecules of the other organisms cloned to date. The central domain of
      CCT, proposed as the catalytic domain of the CTP-transfer reaction, shows 68-72%
      similarity and 48-55% identity among P. falciparum, human, rat and yeast enzymes.
      This gene is present in a single copy, as determined by Southern-blotting of
      genomic DNA, and located on chromosome 13 of P. falciparum. Large transcripts
      were detected by Northern analysis and indicate that this gene is expressed in
      the asexual intraerythrocytic stages. The coding region of the P. falciparum CCT
      gene was inserted into an Escherichia coli expression vector to confirm the
      function of the CCT product. The recombinant CCT expressed in E. coli is
      catalytically active, as evidenced by the conversion of phosphocholine to CDP
      choline.

PMID- 7588776
TI  - DNA binding through distinct domains of zinc-finger-homeodomain protein AREB6 has
      different effects on gene transcription.
AB  - Transcription factor AREB6 has a unique structure composed of two zinc-finger
      clusters in N- and C-terminal regions, and one homeodomain in the middle. AREB6
      has been known to regulate the expression of the Na, K-ATPase alpha 1 subunit,
      interleukin 2 and delta-crystallin genes. We determined the optimal binding sites
      for the N-terminal zinc-finger cluster as GTCACCTGT or TGCACCTGT and for the C
      terminal zinc-finger cluster as C/TACCTG/TT by the CASTing method (cyclic
      amplification and selection of targets). The additional consensus sequence
      GTTTC/G, in conjunction with the CACCTGT sequence, was selected by the second
      CASTing for the entire coding region. The N-terminal zinc-finger cluster binds to
      DNA strongly when the DNA has GTTTC/G in conjunction with the CACCTGT sequence.
      The homeodomain had no specific DNA binding activity but was found to interact
      with the N-terminal zinc-finger cluster. Analyses of zinc-finger mutation
      proteins revealed that the contribution to DNA binding of each N-terminal zinc
      finger motif is altered depending on the presence of the additional consensus.
      Transient transfection assays showed that AREB6 repressed the human 70-kDa heat
      shock gene promoter harboring the CACCTGT sequence together with the additional
      consensus, and that AREB6 activated the promoter harboring the CACCTGT sequence
      without the additional consensus. These results suggest that AREB6 has multiple
      conformational states, leading to positive and negative regulations of gene
      transcription.

PMID- 7588777
TI  - Phosphorylation state of the RNA polymerase II C-terminal domain (CTD) in heat
      shocked cells. Possible involvement of the stress-activated mitogen-activated
      protein (MAP) kinases.
AB  - RNA polymerase (RNAP) II is a multisubunit enzyme composed of several different
      subunits. Phosphorylation of the C-terminal domain (CTD) of the largest subunit
      is tightly regulated. In quiescent or in exponentially growing cells, both the
      unphosphorylated (IIa) and the multiphosphorylated (IIo) subunits of RNAP II are
      found in equivalent amounts as the result of the equilibrated antagonist action
      of protein kinases and phosphatases. In Drosophila and mammalian cells, heat
      shock markedly modifies the phosphorylation of the RNAP II CTD. Mild heat shocks
      result in dephosphorylation of the RNAP II CTD. This dephosphorylation is blocked
      in the presence of actinomycin D, as the CTD dephosphorylation observed in the
      presence of protein kinase inhibitors. Thus, heat shock might inactivate CTD
      kinases which are operative at normal growth temperatures, as some protein kinase
      inhibitors do. In contrast, severe heat shocks are found to increase the amount
      of phosphorylated subunit independently of the transcriptional activity of the
      cells. Mild and severe heat shocks activate protein kinases, which then
      phosphorylate, in vitro and in vivo, the CTD fused to beta-galactosidase. Most of
      the heat-shock-activated CTD kinases present in cytosolic lysates co-purify with
      the activated mitogen-activated protein (MAP) kinases, p42mapk and p44mapk. The
      weak CTD kinase activation occurring upon mild heat shock might be insufficient
      to compensate for the heat inactivation of the already existing CTD kinases.
      However, under severe stress, the MAP kinases are strongly heat activated and
      might prevail over the phosphatases. A survey of different cells and different
      heat-shock conditions shows that the RNAP II CTD hyperphosphorylation rates
      follow the extent of MAP kinase activation. These observations lead to the
      proposal that the RNAP II CTD might be an in vivo target for the activated
      p42mapk and p44mapk MAP kinases.

PMID- 7588778
TI  - Calpain-induced proteolysis of normal human tau and tau associated with paired
      helical filaments.
AB  - The major components of neurofibrillary tangles (NFT) in Alzheimer's disease are
      bundles of paired helical filaments (PHF) which are primarily composed of highly
      phosphorylated tau proteins (PHF-tau). To further understand the mechanism of PHF
      accumulation in NFT, we examined the calpain-induced proteolysis of highly
      purified and primarily non-aggregated PHF and normal tau proteins with various
      contents of phosphate isolated from either fetal (F-tau) or adult human brain (N
      tau). The extent of proteolysis was determined by decreases in tau
      immunoreactivity using Western-blot analysis and a panel of site-specific tau
      antibodies (Alz 50, Tau-2, Tau 14, Tau-1, AT8, E-11, AH-1 and PHF-1). We found
      that full-size polypeptides of N-tau and F-tau were similarly and rapidly
      proteolyzed in vitro by calpain (calpain II, 3.3 units/mg protein) during a 10
      min incubation at 30 degrees C, and that their half lives (t1/2) were 1.5 min and
      1.8 min, respectively. Analysis of immunoblots suggests that full-length
      polypeptides of tau are first degraded into large fragments similar in size to
      that generated endogenously, then into smaller fragments. Since both endogenous
      and in-vitro-generated tau fragments retained N-terminal epitopes, the results
      suggest that most of the calpain-sensitive sites may be located in the C-terminal
      half of the tau molecule. In contrast, PHF were extremely resistant to
      degradation and only a fivefold higher concentration of calpain (16.7 units/mg
      protein) induced partial proteolysis of PHF. A major calpain-generated fragment
      was a 45-kDa polypeptide derived from the C-terminal region of PHF-tau, which
      forms a core of filaments. The results suggest that the inaccessibility of
      potential calpain-digestion sites in the filament core could contribute to the
      resistance of PHF to calpain and subsequently lead to the accumulation of PHF in
      Alzheimer's disease. The results also suggest that hyperphosphorylation of tau
      may be marginally involved in the resistance of PHF to degradation by calpain.
      Ultrastructural examination revealed that, in contrast to previous studies with
      trypsin, calpain did not alter the morphologic appearance of filaments; after
      incubation with calpain, the majority of PHF remained short and disperse and the
      number of PHF aggregated into NFT-like clusters was not significantly increased.
      The results suggest that the role of calpain in promoting the aggregation and
      clustering of filaments is limited.

PMID- 7588779
TI  - Complete amino acid sequence of the Aa6 subunit of the scorpion Androctonus
      australis hemocyanin determined by Edman degradation and mass spectrometry.
AB  - The primary structure of the hemocyanin Aa6 subunit from the scorpion Androctonus
      australis was resolved by using protein sequencing and mass spectrometry for
      analysis of the polypeptide chain and of fragments obtained by CNBr, trypsin, and
      chymotrypsin cleavage. Due to the high sensitivity of the methodologies used,
      only a small amount of material, less than 1 mg, was consumed. The complete
      sequence is composed of 626 amino acid residues and the protein is not
      glycosylated but probably phosphorylated at Ser374. Its molecular mass measured
      by mass spectrometry (71,890 +/- 7 Da) is about 30 Da higher than the mass
      calculated from the sequence data (71,860.1 Da). The origin of this difference is
      not clear but could result from minor molecular heterogeneities. Within the
      chelicerates, the Aa6 subunit of the arachnid A. australis shares 405 identical
      residues with chain e of another arachnid, Eurypelma californicum, and 399 with
      chain alpha of the merostom Tachypleus tridentatus. The degrees of identity
      between these three subunits, which are known to occupy the same location in the
      native hemocyanin oligomers, are significantly higher than those existing between
      the subunits a, d, and e of E. californicum. This favors the hypothesis that gene
      duplications, leading to separate chains in one species, have occurred before the
      divergence between arachnids and merostoms.

PMID- 7588780
TI  - Effects of ionic strength and pH on the binding of medium-chain fatty acids to
      human serum albumin.
AB  - Binding equilibria for the interactions of the medium-chain fatty acid anions,
      laurate and myristate, with defatted human serum albumin have been investigated
      under varying environmental conditions such as ionic strength and pH. Since these
      ligands bind strongly to albumin (Kass approximately 10(7) M-1), conventional
      equilibrium dialysis is not a feasible method for these investigations.
      Consequently, we employed a dialysis method, allowing determination of very low
      concentrations of unbound ligand by measuring the rate of exchange of labelled
      ligand across a dialysis membrane under conditions of chemical equilibrium. Over
      a range of ionic strength, 8-68 mM, the binding of the first few molecules of
      laurate to albumin was weakened with increasing ionic strength, whereas the
      binding of subsequent molecules seemed to proceed independently of ionic
      strength. The binding of myristate by albumin, however, appeared to be
      independent of ionic strength in the observed range of concentrations. The
      influence of pH in the range 5.1-9.0 on the binding of the two fatty acid anions
      by albumin was more complicated. The first molecule of laurate appeared to bind
      with a slightly weaker affinity to albumin at low pH, compared to pH 7 and high
      pH, while the trends for the following molecules varied. The binding of myristate
      (irrespective of concentration) seemed to strengthen monotonously with pH, but
      this conclusion depends critically on the interpretation of the kinetic behaviour
      of the myristate anion. We have previously shown [Pedersen, A. O., Honore, B. &
      Brodersen, R. (1990) Eur. J. Biochem. 190, 497-502] that the strength of binding
      of the first few molecules of the two fatty acid anions to albumin decreases with
      increasing temperature, whereas binding of subsequent molecules seems to proceed
      independently of temperature. We explain these findings as follows. The binding
      of the first few (3 or 4) molecules of the C12 laurate anion is clearly driven by
      formation of ionic bonds between the fatty acid anion and positively charged
      groups, such as lysine residues, in the albumin molecule, whereas the binding of
      subsequent molecules of laurate seems to depend more on hydrophobic interactions.
      In the case of the C14 myristate anion, the binding of the first few (only 1 or
      2) molecules may depend on ionic forces, but binding of the following molecules
      of myristate seems to depend on hydrophobic interactions only.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7588781
TI  - Molecular cloning, expression, and characterization of a human intestinal 15-kDa
      protein.
AB  - We have isolated a cDNA encoding a human intestinal 15-kDa protein (I-15P) from a
      human ileal lambda gt 11 cDNA library, using a full-length rat I-15P cDNA. One
      clone encompassed 571 nucleotides and encoded a 128-amino-acid protein with a
      calculated molecular mass of 14355 Da. The deduced amino acid sequence of human I
      15P showed high similarity to the rat counterpart (78%), mouse ileal lipid
      binding protein (80%) and porcine gastrotropin (75%). It also exhibited 36%
      similarity to human liver fatty-acid-binding protein (L-FABP). Northern blot
      analysis of human I-15P revealed a single transcript only in ileum, however, the
      reverse-transcription/PCR demonstrated expression in ovary and placenta, but it
      was much lower than in ileum. Transformation of Escherichia coli with the I-15P
      cDNA resulted in the efficient expression of a protein that was identical to the
      ileal cytosolic I-15P. In vitro binding studies revealed that the bacterially
      expressed recombinant I-15P showed much lower affinities for palmitate and oleate
      than L-FABP. However, it showed similar affinity for taurocholate, compared with
      a control, BSA. Comparison of the structural features of human I-15P and human L
      FABP suggested that loss of a long alpha-helix region and hydrophobic profile of
      I-15P may be attributable to a unique ligand-binding specificity of I-15P.

PMID- 7588782
TI  - Properties and functions of a neuromedin-B-preferring bombesin receptor in brain
      microvascular endothelial cells.
AB  - Endothelial cells were isolated from rat brain microvessels and grown in vitro.
      They expressed a high density of [125I-Tyr4]bombesin receptor (Bmax = 0.9 pmol/mg
      protein) with an apparent Kd value of 10 nM. The pharmacological profile of
      inhibition of the specific [125I-Tyr4]bombesin binding [bombesin = neuromedin B >
      gastrin releasing peptide (GRP)] was consistent with the presence of a neuromedin
      B-preferring receptor. Addition of bombesin, neuromedin B and GRP increased the
      activity of phospholipase C as measured by the production of total inositol
      phosphates and from intracellular Ca2+ measurements. They increase 86Rb+ uptake
      by the Na+, K+, 2Cl- cotransporter and by a charybdotoxin-sensitive, Ca(2+)
      activated K+ channel and 22Na+ uptake by the Na+/H+ exchanger. The
      pharmacological profiles of activation of phospholipase C, Na+, K+, 2Cl-
      cotransport and Na+/H+ exchange by bombesin-like peptide were consistent with an
      involvement of the neuromedin-B-preferring receptor characterized in binding
      experiments. It is suggested that one of the actions of neuromedin B in brain
      vessels could be to control K+ secretion by the blood/brain barrier.

PMID- 7588784
TI  - Phosphorylation of myosin regulatory light chains by the molluscan twitchin
      kinase.
AB  - The unusually large (approximately 600 to > 3000 kDa) myosin-associated proteins
      of the titin/twitchin superfamily are considered to be important cytoskeletal
      rulers for thick filament assembly in muscle. This function is maintained by
      approximately 60-240 modular fibronectin-type-III and immunoglobulin-C2 repeats
      in these proteins which further contain a protein serine/threonine kinase domain
      of unknown function. In this study, the bacterially expressed kinase domain of
      Aplysia twitchin was used in order to identify a potential physiological
      substrate. Addition of the recombinant kinase to Aplysia actomyosin preparations
      resulted in the specific phosphorylation of the 19-kDa myosin regulatory light
      chains. The twitchin kinase phosphorylated purified light chains on Thr15 in a
      region which shared a high degree of similarity with the phosphorylation site for
      vertebrate smooth muscle myosin light chain kinase. Peptide analogs of the
      twitchin substrate sequence and the similar sequence in vertebrate smooth muscle
      myosin light chains were phosphorylated with good kinetic properties. These data
      reveal the first potential substrate for any of the giant protein kinases and
      support a dual role of twitchin in molluscan muscle as a cytoskeletal protein as
      well as a myosin light chain kinase.

PMID- 7588785
TI  - The purification, characterization and analysis of primary and secondary
      structure of prolyl oligopeptidase from human lymphocytes. Evidence that the
      enzyme belongs to the alpha/beta hydrolase fold family.
AB  - Prolyl oligopeptidase was isolated and purified to homogeneity from human
      lymphocytes, yielding a specific activity of 7780 mU/mg. The molecular mass using
      size-exclusion chromatography matches the 76 kDa obtained by SDS/PAGE. This
      provides evidence that prolyl oligopeptidase is a monomer. The isoelectric point
      is 4.8 as judged by isoelectric focusing in free solution. Di-isopropyl
      fluorophosphate and phenylmethylsulphonyl fluoride completely abolish the
      activity, classifying the enzyme as a serine proteinase. The inhibition by p
      chloromercuribenzoic acid indicates the importance of a free sulfhydryl group
      near the active-site. alpha 1-Casein and ornithine decarboxylase, two proteins
      containing a PEST sequence, inhibit prolyl oligopeptidase, but were not
      hydrolyzed. This demonstrates that prolyl oligopeptidase is not participating in
      the metabolism of proteins according to a PEST-dependent pathway. alpha 1
      Antitrypsin partially inhibits the enzyme but in contrast, aprotinin does not.
      Its inability to cleave corticotropin-releasing factor, ubiquitin, albumin and
      aprotinin, together with the hydrolysis of bradykinin between Pro7-Arg8 confirms
      the affinity of prolyl oligopeptidase for small peptides. Multiple sequence
      alignment does not reveal any similarity with proteases of known tertiary
      structure. Secondary-structure prediction displays striking similarity with
      dipeptidyl peptidase IV and acylaminoacyl peptidase. Two characteristic features
      of the members of the prolyl oligopeptidase family of serine proteases are high
      lighted: the linear arrangement of the catalytic triad is nucleophile-acid-base
      and the proteolytic cleavage releasing the catalytically active C-terminal region
      of around 500 amino acids from the N-terminal sequence. Secondary structure
      prediction and comparison of the active-site of serine proteinases with known
      three-dimensional coordinates prove that Asp641 is the third member of the
      catalytic triad. The secondary structural organization of the protease domain of
      prolyl oligopeptidase is in accordance with the alpha/beta hydrolase fold.

PMID- 7588786
TI  - High efficiency of glycerol 2-phosphate and sn-glycerol 3-phosphate as
      nucleotidyl acceptors in snake venom phosphodiesterase esterifications. Formation
      of primary and secondary AMP-O-glyceryl and AMP-O-glycerophosphoryl esters and
      evidence for an acceptor-binding enzyme site.
AB  - Snake venom phosphodiesterase (SVP) catalyzes the alcoholysis of ATP by primary R
      CH2OH alcohols with uncharged R residues, yielding AMP-O-CH2R esterification
      products. The alcohols compete with water for an SVP-bound adenylyl intermediate.
      In this study, it has been shown that SVP also catalyzes the reactions of
      glycerol 2-phosphate and sn-glycerol 3-phosphate with ATP to yield AMP-O
      glycerophosphoryl esters. The products were identified by HPLC, the dependency of
      the reactions on glycerol phosphates, ultraviolet spectroscopy, and conversion to
      AMP by phosphodiesterase, or to AMP-O-glyceryl esters by alkaline phosphatase.
      The results demonstrated that R-CH2OH alcohols with negatively charged R
      residues, as well as secondary alcohols, act as adenylyl acceptors in SVP
      reactions, thus extending the usefulness of SVP as a tool to produce 5'
      nucleotide derivatives. The efficiencies (EA) of glycerol phosphates as adenylyl
      acceptors were very high at low, millimolar concentrations, but decreased
      abruptly when the acceptor concentration was increased and, for glycerol 2
      phosphate, when Pi or NaCl was present. In contrast, glycerol EA was independent
      of its own concentration, Pi, and NaCl. The responses of glycerol phosphates
      indicate that they act as adenylyl acceptors via a mechanism different from
      uncharged R-CH2OH alcohols. The occurrence of an acceptor-binding enzyme site,
      specific for negatively charged R residues, and its potential relevance to the in
      vivo role of 5'-nucleotide phosphodiesterases as 5'-nucleotidyl transferases are
      discussed.

PMID- 7588783
TI  - The identification of the single-stranded DNA-binding domain of the Escherichia
      coli RecA protein.
AB  - To identify the ssDNA-binding domain of Escherichia coli RecA protein, we
      examined the ssDNA-binding capabilities of synthetic peptides, the sequences of
      which were derived from the C- and N-termini and from sequences within loops L1
      and L2 of the RecA molecule identified from the crystal structure. Synthetic
      peptides derived from amino acid residues 185-219 of several bacterial RecA
      proteins, which include loop L2 of RecA, bound to ssDNA in filter-binding assays,
      whereas three separate synthetic peptides corresponding to single point mutants
      of E. coli RecA in this region did not. The binding of RecA to ssDNA examined
      using a gel-shift assay was inhibited by a synthetic peptide derived from this
      ssDNA-binding region, but not by synthetic peptides derived from amino acid
      residues 301-329 of the C-terminus or from N-terminal residues 6-39. A peptide
      corresponding to amino acid positions 152-169 of the RecA molecule and spanning
      loop L1 and its flanking regions did not bind ssDNA at peptide concentrations up
      to 250 microM. We have also defined a synthetic 20-amino-acid peptide that
      comprises amino acid residues 193-212 and includes loop L2 of RecA as the minimum
      unit that can bind to ssDNA from this region of RecA. Finally, two maltose
      binding protein-RecA fusion proteins were made, one containing amino acid
      residues 185-224 of RecA and the other the last 51 C-terminal residues of RecA
      (amino acid residues 303-353). In contrast to the C-terminus-derived fusion
      protein, the fusion protein containing the putative DNA-binding site demonstrated
      significant binding to single-stranded oligonucleotides in both filter-binding
      and gel-shift assays. These findings suggest that a portion of the region
      extending from amino acid residues 193-212 is either part of or the whole ssDNA
      binding domain of the RecA protein.

PMID- 7588787
TI  - The myristoylated alanine-rich C-kinase substrate (MARCKS) is sequentially
      phosphorylated by conventional, novel and atypical isotypes of protein kinase C.
AB  - The myristoylated alanine-rich C-kinase substrate (MARCKS) is the major protein
      kinase C (PKC) substrate in many cell types including fibroblasts and brain
      cells. Here we describe the phosphorylation of MARCKS and the site specificity
      for different PKC isotypes. Conventional (c)PKC beta 1, novel (n)PKC delta and
      nPKC epsilon efficiently phosphorylated the MARCKS protein in vitro. The Km
      values were extremely low, reflecting a high affinity between kinases and
      substrate. The apparent affinity of nPKC delta (Km = 0.06 microM) was higher than
      that of nPKC epsilon and cPKC beta 1 (Km = 0.32 microM). The rate of substrate
      phosphorylation was inversely correlated with affinity and decreased in the order
      nPKC epsilon > cPKC beta 1 > nPKC delta. Atypical (a)PKC zeta did not
      phosphorylate the intact MARCKS protein. However, a 25-amino-acid peptide deduced
      from the MARCKS phosphorylation domain, was efficiently phosphorylated by aPKC
      zeta as well as by the other three PKC. Site analysis revealed that only serine
      residues S152, S156 and S163 were phosphorylated, with S163 phosphorylated
      highest, followed by S156 and S152; in contrast, S160 and S167 were not
      phosphorylated. No further PKC phosphorylation sites could be detected in MARCKS.
      The phosphorylation pattern was independent of the type of PKC isotype used.
      Kinetic analysis showed, that MARCKS is sequentially phosphorylated in the order
      S156 > S163 > S152 by cPKC, nPKC and aPKC. There was no dramatic difference in
      the sequential phosphorylation of MARCKS detectable when comparing the four PKC
      isotypes. The results are discussed in the context of the functional significance
      of MARCKS phosphorylation.

PMID- 7588788
TI  - UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosamine-1-phosphate
      transferase is amplified in tunicamycin-resistant soybean cells.
AB  - A tunicamycin-resistant soybean cell line was developed by gradually increasing
      the concentration of tunicamycin in the growth medium. At the final stage, the
      resistant cells could survive in media containing 60 micrograms/ml of
      tunicamycin, whereas normal cells show a greatly retarded growth rate at 0.5
      microgram/ml of antibiotic. The tunicamycin-resistant cells had a greater than 40
      fold increase in the activity of the enzyme UDP-GlcNAc:dolichyl-P GlcNAc1P
      transferase, a 2-3-fold increase in the activity of dolichyl-P-mannose synthase,
      but no increase in the activities of other enzymes of the lipid-linked saccharide
      pathway such as dolichyl-P-glucose synthase or mannosyl transferases. There was
      also no change in the activities of the glycoprotein-processing enzymes,
      glucosidase I or glucosidase II, as compared to wild-type cells. The increase in
      GlcNAc1P transferase was due to an increased production of enzyme, as seen by a
      dramatic increase in the amount of a 39-kDa protein, which is presumed to be this
      enzyme protein. The GlcNAc1P transferase from tunicamycin-resistant cells was
      equally sensitive to tunicamycin as was the wild-type enzyme, but was
      considerably more labile to temperatures above 30 degrees C. The activity in
      tunicamycin-resistant cells was greatly stimulated by exogenous dolichyl-P. The
      spectrum of oligosaccharides from labeled lipid-linked oligosaccharides was
      similar in wild-type and tunicamycin-resistant soybean cells, but the resistant
      cells had significantly greater amounts of the shorter and much lower amounts of
      the larger-sized oligosaccharides.

PMID- 7588789
TI  - Changes in the composition of bilirubin-IX isomers during human prenatal
      development.
AB  - We analyzed the isomeric composition of bilirubin-IX in human fetal bile using
      HPLC. The approximate ratio of the bilirubin-IX isomers obtained from the fetal
      bile at 20 weeks of gestation was IX alpha, 6%; IX beta, 87%; IX gamma, 0.5%; and
      IX delta, 6%. From 15 to 22 weeks, bilirubin-IX beta was predominant and
      bilirubin-IX delta and bilirubin-IX alpha were also present in the bile as minor
      components. By 28 weeks, bilirubin-IX alpha constituted about 50% of the total
      bilirubin. There was a general correlation between fetal age and the proportion
      of bilirubin-IX alpha to bilirubin-IX beta in the bile and the small intestinal
      contents of fetuses. As development proceeded from mid-gestation to near term,
      the isomeric composition dramatically changed, with a decrease in the IX beta
      isomer and a subsequent increment of the IX alpha isomer. In contrast, the IX
      delta isomer changes little. Recently, we identified four forms of biliverdin
      reductase including two biliverdin-IX alpha reductases and two biliverdin-IX beta
      reductases in human liver cytosolic fractions [Yamaguchi, T., Komoda, Y. &
      Nakajima. H. (1994) J. Biol. Chem. 269, 24,343-24,348]. The proportion of the
      total activity of biliverdin-IX beta reductases to that of biliverdin-IX alpha
      reductases was considerably higher in the fetal, than in the adult liver.

PMID- 7588791
TI  - Reconstitution of the Fo complex of Escherichia coli ATP synthase from isolated
      subunits. Varying the number of essential carboxylates by co-incorporation of
      wild-type and mutant subunit c after purification in organic solvent.
AB  - Subunit c of the Escherichia coli F1F0-ATPase, purified in chloroform/methanol
      (2:1), was reconstituted with detergent-solubilized F0 subunits a and b to form a
      functionally active H+ channel. The rates of H+ uptake by the proteoliposomes
      containing the reconstituted F0 complex were comparable to those observed with
      native F0 reconstituted without subunit dissociation. The F0 reconstituted from
      purified subunits was also shown to form an active ATP-driven H+ pump upon
      binding of the F1-ATPase sector of the complex. Reconstitution of D61N and D61G
      mutant c subunits with wild-type subunits a and b produced an inactive F0. Hybrid
      F0 complexes, formed with mixtures of wild-type and D61N or D61G mutant c
      subunits, were also prepared. Formation of an active F0 was prevented by addition
      of relatively small proportions of D61N or D61G mutant c subunits, i.e. active F0
      formation was gradually disrupted as the mutant/wild-type ratio was increased
      from 0.05 to 0.2. The hybrid reconstitution studies support a model where
      inactivation of one of the 9-12 c subunits found in F0 is sufficient to abolish
      activity.

PMID- 7588790
TI  - Structural elucidation of the O-antigenic polysaccharide from Escherichia coli
      O44:H18.
AB  - The O-antigen polysaccharide of the lipopolysaccharide from the enteroaggregative
      Escherichia coli O44:H18 has been investigated. Sugar and methylation analysis,
      1H- and 13C-NMR spectroscopy revealed that the polysaccharide is composed of
      pentasaccharide repeating units. The sequence of sugar residues was determined by
      use of two-dimensional nuclear Overhauser effect spectroscopy and heteronuclear
      multiple bond correlation experiments. The structure of the repeating unit of the
      O-antigen from Escherichia coli O44:H18 is as follows. [formula: see text]

PMID- 7588792
TI  - Molecular characterization of Api g 1, the major allergen of celery (Apium
      graveolens), and its immunological and structural relationships to a group of 17
      kDa tree pollen allergens.
AB  - Individuals suffering from immediate hypersensitivity (type-I allergy) to a
      particular pollen frequently display intolerance to several foods of plant
      origin. In this respect, individuals sensitized to birch pollen and/or mugwort
      pollen frequently display type-I allergic symptoms after ingestion of celery. In
      this study, we expressed the major allergenic protein of celery, Api g 1, which
      is responsible for the birch-celery syndrome, in the form of a non-fusion
      protein. The open reading frame of the cDNA of Api g 1 codes for a protein of 153
      amino acids with a molecular mass of 16.2 kDa and 40% identity (60% similarity)
      to the major allergen of birch pollen, Bet v 1. Furthermore, Api g 1 exhibited
      similar characteristics to (a) two proteins in parsley induced by fungal
      infection, (b) the major tree pollen allergens and (c) pathogenesis-related and
      stress-induced proteins in other plant species. The reactivity of recombinant Api
      g 1 with IgE antibodies present in sera from celery intolerant patients was
      comparable to that of the natural celery allergen. Cross-reactivity with Bet v 1
      was proven by cross-inhibition experiments, which provides further support for
      the existence of the birch-celery syndrome and for the suggestion that allergies
      to some vegetable foods are epiphenomena to allergies caused by inhalation of
      tree pollen.

PMID- 7588793
TI  - Purification and characterization of acid cysteine protease from metacercariae of
      the mammalian trematode parasite Paragonimus westermani.
AB  - Acid cysteine protease was purified from metacercariae of the mammalian trematode
      parasite Paragonimus westermani. The purified enzyme had a molecular mass of 27
      kDa and was a monomeric polypeptide. The protease had an absolute requirement for
      a reducing agent for full activity towards fluorescein-isothiocyanate-labeled
      hemoglobin, and it was active in the acidic pH range, with an optimum pH of 4.0.
      While acidic proteolysis was insensitive to the aspartic protease inhibitor
      pepstatin A, activity was significantly inhibited by the cysteine protease
      inhibitors, leupeptin, chymostatin and L-trans-epoxy-succinyl-L-leucylamido(4
      guanidino)-butane. The sensitivity of the enzyme to the inhibitors was similar to
      that of cathepsins B and L, but the specificity of the protease towards
      chromogenic substrates was slightly different from that of the cathepsins. The
      purified enzyme was highly specific for N-substituted peptidyl substrates
      containing arginine in the P1 position and phenylalanine in the P2 position, and
      the protease extensively degraded human native proteins, such as human serum
      albumin, immunoglobulins, complement components and also endogenous protease
      inhibitors. Since the protease hydrolyzes both soluble proteins and components of
      human defense systems, it may facilitate parasite nutrition and evasion of host
      defense mechanisms.

PMID- 7588794
TI  - Involvement of the C-terminal tail in the activity of Drosophila alcohol
      dehydrogenase. Evaluation of truncated proteins constructed by site-directed
      mutagenesis.
AB  - Drosophila alcohol dehydrogenase belongs to the heterogeneous family of short
      chain dehydrogenases/reductases, which does not include the well characterized
      mammalian alcohol dehydrogenases. Although it is clear that the main biological
      role of this enzyme is in alcohol oxidation, in the absence of the three
      dimensional conformation only partial information on the protein regions involved
      in the active site, and the coenzyme and substrate interacting cavities is
      available. Two segments have already been identified, a coenzyme-binding segment
      at the N-terminus, and the reactive Tyr152 and Lys156 residues. Limited
      proteolytic assays had suggested the involvement of the 13 C-terminal amino acids
      in the function of the enzyme. By site-directed mutagenesis, we have constructed
      eight different truncated mutant enzymes and expressed them in Escherichia coli.
      The purified mutant enzymes have been recovered and characterized using
      monoclonal antibodies. Kinetic analysis and stability assays have been performed,
      and clearly demonstrate the contribution of the last 13 amino acids to the
      activity. We hypothesize that the C-terminal tail constitutes an essential region
      for maintaining the hydrophobicity of the catalytic pocket needed for binding of
      the substrate.

PMID- 7588795
TI  - Bacterial expression of the catalytic domain of 3-hydroxy-3-methylglutaryl-CoA
      reductase (isoform HMGR1) from Arabidopsis thaliana, and its inactivation by
      phosphorylation at Ser577 by Brassica oleracea 3-hydroxy-3-methylglutaryl-CoA
      reductase kinase.
AB  - The catalytic domain of 3-hydroxy-3-methylglutaryl-CoA reductase isoform 1
      (HMGR1cd) from Arabidopsis thaliana has been expressed in Escherichia coli in a
      catalytically active form and purified. The high efficiency of the bacterial
      expression system together with the simplicity of the purification procedure used
      in this study resulted in the attainment of large quantities of pure enzyme
      (about 5 mg/l culture) with a final specific activity of up to 17 U/mg. This
      specific activity is higher than that reported to date for any 3-hydroxy-3
      methylglutaryl-CoA reductase (HMGR) purified from a plant source. HMGR1cd
      activity was completely blocked by the HMGR inhibitor mevinolin (IC50 = 12.5 nM).
      No significant differences were observed between the Km values of HMGR1cd for
      NADPH (71 +/- 7 microM) and (S)-3-hydroxy-3-methylglutaryl-CoA (8.3 +/- 1.5
      microM) and those of pure HMGR preparations obtained from different plant
      sources. The purified HMGR1cd was reversibly inactivated by phosphorylation at a
      single site by Brassica oleracea HMGR kinase A, which is functionally related to
      the mammalian AMP-activated protein kinase. The site of phosphorylation is Ser577
      in the complete sequence of A. thaliana HMGR1. The results in this paper
      represent the first evidence that a higher plant HMGR is regulated by direct
      phosphorylation, at least in a cell-free system. Our results also reinforce the
      view that the AMP-activated protein kinase/SNF1 family is an ancient and highly
      conserved protein kinase system.

PMID- 7588796
TI  - Urokinase-type plasminogen activator/type-2 plasminogen-activator inhibitor
      complexes are not internalized upon binding to the urokinase-type-plasminogen
      activator receptor in THP-1 cells. Interaction of urokinase-type plasminogen
      activator/type-2 plasminogen-activator inhibitor complexes with the cell surface.
AB  - The urokinase-type plasminogen activator (uPA) and its inhibitor PAI-2 form a
      covalent complex that, upon binding to the uPA receptor (uPA-R), is cleaved into
      two fragments of molecular masses 70 kDa and 22 kDa. The 70-kDa fragment results
      from the interaction of the B chain of uPA and PAI-2 whereas the 22-kDa fragment
      is the A chain of the enzyme [13]. We prove that, at 37 degrees C, the 70-kDa
      fragment is released into the medium, whereas the 22-kDa fragment remains bound
      to the cell surface. uPA complexed with its other specific inhibitor, PAI-1, is
      cleaved into fragments of identical sizes, but the 70-kDa component is
      internalized via the alpha 2-macroglobulin receptor. At 4 degrees C, both uPA/PAI
      2 complex degradation products remain bound to the uPA-R. We propose that the 70
      kDa molecule, which lacks the uPA binding region for uPA-R, is bound to uPA-R via
      a new binding site, unmasked only when uPA-R is occupied by uPA/PAI-2 complexes.

PMID- 7588797
TI  - Genetic and biochemical characterization of the UGP1 gene encoding the UDP
      glucose pyrophosphorylase from Saccharomyces cerevisiae.
AB  - We report here that the open reading frame YKL248, previously identified during
      the systematic sequencing of yeast chromosome XI [Purnelle B., Skala, J., Van
      Dijck, L. & Goffeau, A. (1992) Yeast 8, 977-986] encodes UDP-glucose
      pyrophosphorylase (UGPase), the enzyme which catalyses the reversible formation
      of UDP-Glc from glucose 1-phosphate and UTP. Proof for this function come from
      sequence alignment of the YKL248 product with UGPase of other species, from
      complementation studies of an Escherichia coli galU mutant deficient in UGPase
      activity, and from overexpression studies. In particular, the amino acid sequence
      motifs involved in the binding of glucose 1-phosphate and UDP-Glc are entirely
      conserved between the yeast, bovine, human and potato tuber UGPases, and multi
      copy expression of YKL248 resulted in a 40-fold increase in UGPase activity. This
      gene was, therefore, renamed UGP1. Gene disruption at the UGP1 locus in a diploid
      strain, followed by tetrad analysis, showed that UGPase is essential for cell
      viability. Functional analysis of UGP1 was, therefore, carried out by generating
      strains in which UGPase could be either overexpressed or depleted. This was done
      by generating haploid strains carrying either UGP1 on a multicopy vector or the
      chromosomal deletion of UGP1, and rescued by a vector bearing the wild-type gene
      under the control of the glucose-repressible galactose-inducible promoter. The
      effects of overproducing UGPase on the cell metabolism and morphology were carbon
      source dependent. On glucose medium, the 40-fold increase of UGPase activity was
      restricted to a twofold increase in the concentration of glycogen and UDP-Glc,
      with no significant effect on growth. In contrast, on galactose, the 40-fold
      increase in UGPase activity was accompanied by several effects, including a
      threefold reduction of the growth rate, a 3-5-fold increase in the concentrations
      of UDP-Glc, UDP-Gal and galactose 1-phosphate, a higher sensitivity to calcofluor
      white and an increase in the degree of protein glycosylation. Depletion of UGPase
      activity was performed by transferring the mutant strains from galactose to
      glucose medium. Unexpectedly, growth of these mutants on glucose was as efficient
      as that of the control, although the mutants contained only 5-10% wild-type
      UGPase activity, and a growth defect could never been obtained, even after serial
      transfers of the mutants to a 10% glucose medium. However, the 10-fold reduction
      of UGPase activity induced a multi-budding pattern, a higher resistance to
      zymolyase, a slight increase in the calcofluor sensitivity and a decrease in the
      cell-wall beta-glucan content. All these alterations, induced by manipulating the
      UGP1 gene, are discussed in the context of the strategic position of UDP-Glc in
      yeast metabolism.

PMID- 7588798
TI  - New inhibitors of the ubiquinol oxidase of higher plant mitochondria.
AB  - A screen has been performed of possible inhibitors of the ubiquinol oxidase of
      higher plant mitochondria by assaying their effects on cyanide-insensitive NADH
      oxidase of mitochondria of Arum maculatum. A number of compounds which have
      powerful inhibitory effects have been identified. Potent inhibition was found
      with compounds related to the previously described n-propyl gallate, but with the
      n-propyl sidechain replaced with alkyl chains of greater hydrophobicity.
      Titration of a range of partial reactions showed that the inhibitors act
      specifically on the ubiquinol oxidase. The concentrations of inhibitor required
      are dependent on the respiratory substrate and on the amount of mitochondria used
      in the assay. Octyl gallate also proved to be a potent inhibitor of the ubiquinol
      oxidase in tobacco cell suspensions. A second class of compounds which strongly
      inhibit cyanide-insensitive NADH oxidation is aurachin C and its analogues.
      Compounds related to aurachin D are much less effective. Titrations of a range of
      partial reactions indicate that inhibition is caused by a direct action on the
      ubiquinol oxidase. However, both types of aurachins also act strongly at the Qi
      site of the cytochrome bc1 complex, as already known to be the case in other
      systems, and so they are of more limited value for studies of the ubiquinol
      oxidase. Titration of the oxidation of NADH via the ubiquinol oxidase in a
      purified mitochondrial fraction from the spadices of Arum maculatum with octyl
      gallate gave a half-maximal effect at a concentration of around 6 nM when the
      protein concentration was 14 micrograms ml-1. A similar titre was obtained with a
      decyl derivative of aurachin C. This allowed us to estimate an upper limit for
      the concentration of ubiquinol oxidase in these mitochondria of 0.72 +/- 0.15
      nmol mg-1 protein, or a ratio of ubiquinol oxidase/cytochrome oxidase of about 15
      +/- 7:1. The measurements also provide a minimal turnover number for the
      ubiquinol oxidase of 186 +/- 42 electrons.s-1. Titration of the ubiquinol oxidase
      in soybean cotyledon mitochondria with these compounds gave the concentration of
      inhibitor required to elicit 50% of the maximum observed effect (I50) values
      about one order of magnitude higher than those found with Arum mitochondria, and
      again the values depended on the respiratory substrate. An explanation for the
      variation in I50 values may be found in terms of differences in oxidase
      concentrations in the different mitochondrial membranes and in the differences in
      rate-controlling steps with substrates of different activities.

PMID- 7588799
TI  - Quantitative analysis of the pyrimidine metabolism in pheochromocytoma PC-12
      cells.
AB  - A detailed quantitative study of pyrimidine metabolism in exponentially growing
      rat pheochromocytoma PC-12 cells has been performed. The sizes of ribonucleotide
      pools have been analysed and the pathways and the rates of metabolism of uridine,
      cytidine and aspartic acid have been determined, based on the incorporation of
      radioactive label. The fluxes of radioactive label through uridine-cytidine
      kinase, cytidine deaminase. CTP synthetase, nucleoside monophosphate kinase and
      nucleoside diphosphate kinase were obtained, as well as the flux through the
      pyrimidine de novo pathway. Also, the fluxes of radioactive label towards UDP
      sugars, CDP-compounds, DNA and RNA were quantified in situ under steady-state
      conditions in intact PC-12 cells. From these fluxes of radioactivity,
      distribution ratios at the branch points of the metabolism were obtained. The
      pyrimidines synthesised via the de novo pathway were preferentially used for the
      synthesis of UDP-N-acetylhexosamines and UDP-hexoses, whereas the salvage of
      precursors from the medium contributed, to a large extent, to the synthesis of
      RNA. Therefore, we postulate that at least two different UTP pools exist in these
      cancer cells derived from the neural crest. Furthermore, after metabolism of
      radiolabeled cytidine and uridine into UTP, radiolabel was distributed in a
      similar manner from UTP towards UDP-N-acetylhexosamines, UDP-hexoses and RNA-UMP.
      Uridine, as well as cytidine, was channelled towards nucleic acids via small
      compartmented ribonucleotide pools.

PMID- 7588801
TI  - Structure of metal site in Cd-substituted His117Gly mutant of azurin with and
      without addition of imidazole derivatives.
AB  - The present work uses 111mCd-perturbed angular correlations of gamma-rays (PAC)
      to investigate the structure of the metal site of the His117Gly mutant of
      Pseudomonas aeruginosa azurin in aqueous solution and the effect on the structure
      upon addition of the following exogenous ligands: imidazole, 4-methyl imidazole,
      1-methyl imidazole, 2-methyl imidazole and histidine. The nuclear quadrupole
      interaction of cadmium bound to the mutant without addition of exogenous ligands
      shows a strong pH dependence with three different nuclear quadrupole interactions
      consistent with two pKa values at about 7.2 and 8.6 at 2 degrees C. Addition of
      the imidazole derivatives resulted in a significant change in the PAC spectrum
      showing that they coordinate. This is in accordance with observations by EPR for
      the same mutant with copper at the metal site [den Blaauwen, T. & Canters, G. W.
      (1993) J. Am. Chem. Soc. 115, 1121-1129]. However, whereas EPR and
      ultraviolet/visual absorption show that the characteristics of the wild-type
      copper protein are regained by addition of the imidazole derivatives with the
      exception of the possible bidentates (histidine and histamine), the comparison of
      the PAC results to model calculations shows that the cadmium ion must be fourfold
      coordinated in most cases, probably binding an additional water or hydroxide
      ligand. A fourfold coordination is in contrast to cadmium-substituted wild-type
      azurin where PAC data inferred a threefold coordination by a Cys and two His
      residues [Danielsen, E. Bauer, R., Hemmingsen, L., Andersen. M., Bjerrum, M. J.,
      Butz, T., Troger, W., Canters, G. W., Hoitink, C. W. G., Karlsson, G., Hansson,
      O. & Messerschmidt, A. (1995) J. Biol. Chem. 270, 573-580]

PMID- 7588800
TI  - Structural characterization of an intramolecular RNA triple helix by NMR
      spectroscopy.
AB  - A chemically synthesized 29-base RNA oligomer, designed to fold to form an
      intramolecular triple helix at acid pH, has been studied by NMR spectroscopy. The
      molecule consisted of seven U.A.U or C+.G.C base triples joined by two pyrimidine
      tetra-loops. The fold was such that the third strand was Hoogsteen base-paired in
      the major groove of a Watson-Crick paired double helix. The nature and size of
      the molecule required the use of an assignment strategy using two- and three
      dimensional homonuclear methods, complemented by a natural abundance 13C
      correlation experiment. The assignment of the majority of the exchangeable and
      non-exchangeable resonances is presented. The data suggest a C3'-endo sugar
      puckering for all the nucleotides involved in base triples. A preliminary
      structural model consistent with the NMR data is presented.

PMID- 7588802
TI  - Expression in Aspergillus niger of the starch-binding domain of glucoamylase.
      Comparison with the proteolytically produced starch-binding domain.
AB  - Glucoamylase 1 from Aspergillus niger is an economically important enzyme in many
      industrial processes. It hydrolyses granular starch and comprises two distinct
      domains, a catalytic and a starch-binding domain (SBD). We have transformed A.
      niger with an expression vector for the secretion of SBD for physico-chemical
      studies. This was achieved by introducing into the glucoamylase gene a short
      sequence encoding an endoproteolytic cleavage recognition site such that free SBD
      was secreted at yields up to 200 mg/l. Free SBD was also obtained by proteolytic
      digestion of full-length glucoamylase 1. Electrospray mass spectroscopy was used
      to determine the carbohydrate content of both SBDs. It revealed that the
      engineered one is more glycosylated: an average of three mannose residues
      compared to one for the proteolytically derived SBD. Sequencing results also
      suggest partial glycosylation for the three Thr residues involved (510, 511,
      513). It is probable that the engineered SBD represents the true glycosylation
      level of the SBD in native glucoamylase. Binding of beta-cyclodextrin to the SBD
      was investigated. It was found that the stoichiometry and the spectral
      perturbation of Trp residues were identical for both SBDs, but the engineered SBD
      bound less strongly to the ligand. At high concentrations of beta-cyclodextrin
      relative to the estimated Kd values, the maximum absorbance changes were
      identical. The observed difference at low beta-cyclodextrin levels was probably
      due to the higher level of glycosylation of the expressed SBD. We conclude that
      the proteolytically derived and expressed starch binding domains both bind 2 mol
      beta-cyclodextrin/mol protein, but that the pattern of glycosylation and strength
      of binding are different.

PMID- 7588803
TI  - 1H and 15N assignments and secondary structure of the starch-binding domain of
      glucoamylase from Aspergillus niger.
AB  - 1H and 15N NMR resonance assignments of the granular starch-binding domain (SBD)
      of glucoamylase from Aspergillus niger have been made by multi-dimensional
      homonuclear and heteronuclear NMR techniques. Secondary structure analysis based
      on chemical shifts, 1H-1H NOEs, coupling constants and backbone amide exchange
      data indicates the presence of a well-defined beta-sheet structure. This consists
      of one parallel and five antiparallel pairs of beta-strands forming two beta
      sheets. Cis-trans isomerisation of proline residues and O-glycosylation of
      threonine residues are observed and compared between the proteolytically derived
      SBD fragment and the recombinant protein. Structural features of the SBD in
      solution were compared to the X-ray crystal structure of a homologous domain of
      cyclodextrin glycosyltransferase from Bacillus circulans. There are some
      differences in the locations of the start and end of beta-strands but overall the
      two structures are very similar. This study will form the basis for the structure
      determination of the granular SBD and of its complexes.

PMID- 7588804
TI  - Evidence for elongation of the helical pitch of the RecA filament upon ATP and
      ADP binding using small-angle neutron scattering.
AB  - Structural changes of the RecA filament upon binding of cofactors have been
      investigated by small-angle neutron scattering. Both ATP and ADP increased the
      helical pitch of the RecA homopolymer, which is observed to be 7 nm in the
      absence of any cofactor. The binding of ATP altered the pitch to 9 nm, whereas
      the binding of ADP only produced a pitch of 8.2 nm. The pitch determined for the
      RecA complex with the ATP analog adenosine 5'-[gamma-thio]triphosphate was
      similar to that found with ATP. Thus, at least three, somewhat different. RecA
      helical filamentous structures may form in solution. The binding of DNA to RecA
      did not alter the pitch significantly, indicating that the cofactor binding is
      the determining factor for the size of the helical pitch of the RecA filament. We
      also found that elongation of the helical pitch is a necessary, but not a
      sufficient condition, for the coprotease activity of RecA. The presence of
      acetate or glutamate ions is also required. The pitch of the ADP.RecA filament is
      in agreement with that found in the crystal structure. This correlation indicates
      that this structure corresponds to that of the ADP.RecA filament in solution,
      although this is not the species active in recombination.

PMID- 7588805
TI  - Differential functional activities of rainbow trout and human estrogen receptors
      expressed in the yeast Saccharomyces cerevisiae.
AB  - The cDNA of rainbow trout estrogen receptor (rtER), highly and stably expressed
      in yeast, Saccharomyces cerevisiae, was used to analyse the biological activity
      of the receptor. The rtER mRNA encoded a 65-kDa protein which was immunorevealed
      by a specific antibody and migrated with the authentic rtER major protein form
      detected in trout liver. Yeast rtER bound estradiol with high affinity and the
      dissociation constant (Kd = 1.35 nM) was very similar to the value measured from
      trout liver extracts but 3-5-fold higher than the Kd found for human estrogen
      receptor (hER). This indicates therefore that the rtER has a lower estradiol
      affinity compared to the human receptor. While the hER Kd remained unchanged at
      both 4 degrees C or 22 degrees C, it was slightly modified at 30 degrees C. The
      Kd measured for rtER at 22 degrees C and 30 degrees C were about 2-fold, and 12
      fold higher, respectively, than the Kd obtained at 4 degrees C suggesting an
      alteration of the rtER affinity for its ligand at elevated temperature. To
      examine the estrogen-receptor-mediated activation of transcription in yeast,
      reporter plasmids integrated or not in the yeast genome were used. The reporter
      genes consist of one, two, or three copies of estrogen-responsive elements (ERE)
      upstream of the yeast proximal CYC1 or URA3 promoters fused to the lacZ gene of
      Escherichia coli coding for beta-galactosidase. The induction of beta
      galactosidase activity for all reporter genes was strictly dependent on the
      presence of rtER and estrogens. The activation of transcription mediated by rtER
      responded in an estradiol-dose-dependent manner as in animal cells. However,
      compared to hER, the estradiol concentration necessary to achieve maximal
      activation was 10-fold higher. This is probably a consequence of the lower
      estradiol-affinity for rtER compared to hER. The levels of induction of the
      reporter genes containing two or three ERE were strongly enhanced compared to the
      one ERE construct. This is in agreement with the synergistic effect previously
      described for multiple ERE. The magnitudes of transcriptional induction mediated
      by rtER and hER were similar when the reporter gene containing three ERE was used
      but changed when the one ERE construct was used. In this case transcriptional
      activation indicated by rtER was 10-20 fold lower. This suggests that rtER
      requires protein/protein interaction for its stabilization on DNA. Antiestrogens
      were able to bind rtER and promote gene transcription. However, to produce
      effects comparable to those obtained with estrogens, much higher concentrations
      were required. This may imply nonetheless that antihormones were capable of
      provoking efficient interactions of rtER with the transcriptional machinery.

PMID- 7588806
TI  - The covalent linkage of a viologen to a flavoprotein reductase transforms it into
      an oxidase.
AB  - Chemical cross-linkage of the positively charged viologen N-methyl-N'
      (aminopropyl)-4-4'-bipyridinium dibromide (APMV) to the enzyme ferredoxin-NADP+
      reductase from the cyanobacterium Anabaena PCC 7119 has been performed using the
      carbodiimide 1-ethyl[3-(3-dimethylaminopropyl)]carbodiimide. 0.5-1 mol, depending
      on the preparation, is introduced for each mol enzyme. The residue involved in
      the covalent linkage with the viologen, Glu139, has been identified using HPLC
      separation of the modified proteolytic peptides and subsequent sequencing.
      Modification of the enzyme changes its catalytic specificity since it is able to
      react directly with oxygen; this is observed by a high NADPH oxidase activity,
      which is completely absent in the native enzyme. More important, this new enzymic
      activity is indicative of the intramolecular electron transfer between the
      natural redox cofactor FAD and the artificially introduced viologen. Electrons
      can also flow in the reverse direction, from the viologen to the FAD group, then
      to NADP+, when the reaction is performed using glassy-carbon electrodes to reduce
      the viologen. Cyclic voltammetry experiments have shown that there is a small
      catalytic current between the electrode and the enzyme which is not observed in
      the native enzyme.

PMID- 7588808
TI  - Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer
      cells.
AB  - The product of the MUC1 gene, the polymorphic epithelial mucin (PEM) is
      aberrantly glycosylated in breast and other carcinomas, resulting in exposure of
      normally cryptic peptide epitopes. PEM expressed by breast cancer cells contains
      more sialylated O-glycans and has a lower GlcNAc content than that expressed by
      normal cells. The exposure of peptide epitopes is thus thought to be due to the
      sugar side chains being shorter on the tumour-associated mucin. To investigate
      possible mechanisms underlying the different pattern of glycosylation in breast
      cancer cells, we analysed the pathways involved in the biosynthesis of O-glycan
      chains of mucins in normal and cancerous mammary epithelial cells. An
      immortalized mammary epithelial cells line originating from normal human milk.
      MTSV1-7, and three human breast cancer cell lines, BT20, MCF-7 and T47D, were
      studied. Glycosyltransferase activities assembling, elongating and terminating O
      glycan core-1 [Gal beta 1-3GalNAc alpha-R] and core-2 [GlcNac beta 1-6 (Gal beta
      1-3) GalNAc alpha-R] were present in the normal mammary cell line. Many of the
      glycosyltransferase activities were also expressed at variable levels in breast
      cancer cells. However, a sialyltransferase activity (CMP-sialic acid Gal beta 1
      3GalNAc alpha 3-sialyltransferase) was increased several fold in all three cancer
      cell lines. Moreover, mammary cancer cell lines BT20 and T47D have lost the
      ability to synthesize core-2, as shown by the lack of UDP-GlcNAc: Gal beta 1
      3GalNAc (GlcNAc to GalNAc) beta 6-GlcNAc-transferase activity, which corresponded
      to the absence of the mRNA transcript. However, MCF-7 breast cancer cells
      expressed this enzyme. Thus, the mechanism for the exposure of peptide epitopes
      in BT20 and T47D cells is proposed to be the loss of core-2 branching leading to
      shorter, sialylated O-glycan chains. A different mechanism is proposed for MCF-7
      breast cancer cells.

PMID- 7588809
TI  - Studies of the bound conformations of methyl alpha-lactoside and methyl beta
      allolactoside to ricin B chain using transferred NOE experiments in the
      laboratory and rotating frames, assisted by molecular mechanics and dynamics
      calculations.
AB  - The conformation in solution of methyl beta-galactopyranosyl-(1-->4)-alpha
      glucopyranoside (methyl alpha-lactoside) and methyl beta-galactopyranosyl-(1-->6)
      beta-glucopyranoside (methyl beta-allolactoside) has been studied through NMR
      spectroscopy and molecular mechanics calculations. NOE measurements both in the
      laboratory and rotating frames, have been interpreted in terms of an ensemble
      average distribution of conformers. Molecular mechanics calculations have been
      performed to estimate the probability distribution of conformers from the steric
      energy maps. The experimental results indicate that methyl alpha-lactoside spends
      about 90% of its time in a broad low-energy region close to the global minimum,
      while methyl beta-allolactoside presents much higher flexibility. The
      conformational changes that occur when both disaccharides are bound to the ricin
      B chain in aqueous solution have been studied using transferred NOE experiments
      at several protein/ligand ratios. The observed data indicate that the protein
      causes a conformational variation in the torsion angles of methyl alpha-lactoside
      changing towards smaller angle values (phi/psi approximately -20/-20), although
      the recognized conformer is still within the lowest energy region. In particular,
      the torsional changes separate Gal H1 from Glc H3 and Glc H6 protons, with a
      noticeable decrease in the intensities of the corresponding NOE cross-peaks,
      which were clearly observed for the free disaccharide. On the other hand,
      different conformations around the phi, psi, and omega glycosidic bonds of methyl
      beta-allolactoside are recognized by the lectin. In fact, for the methyl-beta
      allolactoside-ricin-B complex, only the NOESY cross-peaks corresponding to the
      protons of the galactose residue are negative, as expected for a molecule in the
      slow motion regime. In contrast, the corresponding cross peaks for the glucose
      residue were about zero, as expected for a molecule whose motion is practically
      independent of the protein. However, for the methyl-alpha-lactoside-ricin-B
      complex, all the NOESY cross-peaks for both the galactose and glucose moieties
      were clearly negative. From the NMR experimental point of view, it is
      demonstrated that the comparison of longitudinal and transversal transferred NOEs
      allows one to clearly differentiate direct enhancements from spin diffusion
      effects, which are of major concern when analysing NOE spectra of
      macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588810
TI  - Solution structure of the Na+ form of the dimeric guanine quadruplex
      [d(G3T4G3)]2.
AB  - The solution structure of the DNA quadruplex formed by the association of two
      strands of the DNA oligonucleotide, d(G3T4G3), in NaCl solution has been
      determined by 1H two-dimensional NMR techniques, full relaxation matrix
      calculations and restrained molecular dynamics. The refined structure
      incorporates the sequences 5'-G1sG2AG3AT4AT5AT6AT7AG8sG9AG10A-3' and 5'
      G11sG12AG13AT14AT15AT16AT17AG18sG19sG20A-3' (where S and A denote syn and anti,
      respectively) in a three-quartet, diagonal-looped structure that we [Strahan, G.
      D., Shafer, R. H. & Keniry, M. A. (1994) Nucleic Acids Res. 22, 5447-5455] and
      others [Smith, F. W., Lau, F. W. & Feigon, J. (1994) Proc. Natl. Acad. Sci. USA
      91, 10546-10550] have described. The loop structure is compact and incorporates
      many of the features found in duplex hairpin loops including base stacking,
      intraloop hydrogen bonding and extensive van der Waals' interactions. The first
      and third loop thymines stack over the outermost G-quartet and are also
      associated by hydrogen bonding. The second and the fourth loop thymines fold
      inwards in order to enhance van der Waals' interactions. The unexpected
      sequential syn-syn deoxyguanosines in the quadruplex stem appear to be a direct
      consequence of the way DNA oligonucleotides fold and the subsequent search for
      the most stable loop structure. The implications of loop sequence and length on
      the structure of quadruplexes are discussed.

PMID- 7588807
TI  - Compressibility of the heme pocket of substrate analogue complexes of cytochrome
      P-450cam-CO. The effect of hydrostatic pressure on the Soret band.
AB  - The effect of hydrostatic pressure on the electronic absorption spectrum of the
      carbon monoxide complex of cytochrome P-450cam (CYP101) in the presence of
      various substrates was studied. With increasing pressure the wavenumber of the
      Soret band in the cytochrome P-450-CO complex shifts linearily to lower values
      (red-shift) and the half-width increases (broadening). The microscopic theory of
      solvent-solute interaction discussed by Laird and Skinner is used to explain the
      observed pressure effects. According to this theory, the slope of the red-shift
      of the Soret band is related to the compressibility of the chromophore
      environment, that is the heme moiety of the hemoproteins. It was found that the
      slope of the red-shift and the slope of the broadening of the Soret band for the
      CO complex in the presence of various substrate analogues increase with the
      decrease of the initial high-spin content at 0.1 MPa in the oxidized state.
      Variation of the high-spin content reflects the changes in the number of water
      molecules and/or changes in the polarity of the heme environment. The higher
      compressibility of the cytochrome P-450 complexes with the substrate analogues,
      which induce a lower degree of the high-spin content in the oxidized protein, is
      explained by the ability of the water molecules in the heme moiety to transmit
      the pressure effect on the protein structure to the heme chromophore. Therefore,
      a larger pressure-induced red-shift of the Soret band in the CO complex of
      cytochrome P-450cam might indicate a higher water content in the heme
      environment.

PMID- 7588811
TI  - Man9-mannosidase from human kidney is expressed in COS cells as a Golgi-resident
      type II transmembrane N-glycoprotein.
AB  - Man9-mannosidase, an alpha 1,2-specific exo-enzyme involved in N-linked
      oligosaccharide processing, has been cloned recently from a human kidney cDNA
      library [Bause, E., Bieberich, E., Rolfs, A., Volker, C. & Schmidt, B. (1993)
      Eur. J. Biochem. 217, 533-540]. Transient expression in COS 1 cells of the enzyme
      resulted in a more than 20-fold increase of a catalytic activity cleaving
      specifically alpha 1,2-mannosidic linkages in [14C]Man9-GlcNAc2 or [14C]Man5
      GlcNAc2. Man9-mannosidase is expressed as a N-glycoprotein with a molecular mass
      of 73 kDa. Its enzymic activity is metal ion dependent and inhibited strongly by
      1-deoxymannojirimycin (50% at 100 microM). Proteolytic studies with the membrane
      associated form of Man9-mannosidase support the view that the enzyme is a type II
      transmembrane protein as predicted from its cDNA sequence. Several lines of
      evidence suggest that Man9-mannosidase, as expressed, is N-glycosylated at one of
      three potential Asn-Xaa-Thr/Ser/Cys acceptor sites. Approximately 50% of the N
      linked oligosaccharide chains are removed by endoglycosidase H treatment, whereas
      complete deglycosylation of the enzyme is observed, when transfected cells were
      cultured in the presence of the Golgi mannosidase II inhibitor swainsonine,
      indicating that the sugar moiety of Man9-mannosidase is processed partially by
      Golgi-resident enzymes. This observation is consistent with the results of
      indirect immunofluorescence studies, pointing to a localization of the Man9
      mannosidase predominantly in the juxtanuclear Golgi region. This localization
      clearly differs from that of pig liver Man9-mannosidase which appears to be
      located in the endoplasmic reticulum and transient vesicles.

PMID- 7588813
TI  - A Fourier-transform infrared spectroscopic investigation of the hydrogen
      deuterium exchange and secondary structure of the 28-kDa channel-forming integral
      membrane protein (CHIP28).
AB  - Fourier-transform infrared spectroscopy (FTIR) has been employed to investigate
      the structural properties of the 28-kDa channel-forming integral membrane protein
      (CHIP28) present in phospholipid vesicles suspended in aqueous media. This study
      reports the FTIR spectra of this membrane protein present in H2O and 2H2O. The
      secondary structure of the protein was determined and found to consist of 36%
      alpha-helical and 42% beta-sheet structures. These results are in close agreement
      with the results of a previous CD study [Van Hoek, A. N., Wiener, M., Bicknese,
      S., Miercke, L., Biwersi, J. & Verkman, A. S. (1993) Biochemistry 32, 11,847
      11,856]. However, the results differ from those given in an FTIR analysis by the
      same workers who recorded FTIR spectra of the CHIP28 protein in a dehydrated
      state. An unusually high extent of hydrogen-deuterium exchange of the peptide
      groups of this protein occurs. The magnitude of the spectral changes observed
      upon exposure of the protein to 2H2O is greater than has been observed with any
      other membrane protein previously studied. Thus, over 80% of the peptide groups
      exchange within 5 min and the amide I band maximum shifts to low frequency by
      approximately 20 cm-1. This high hydrogen-deuterium exchange observed with the
      CHIP28 protein is consistent with the presence of an aqueous pore within the
      protein structure.

PMID- 7588814
TI  - Nitrite reductase from the magnetotactic bacterium Magnetospirillum
      magnetotacticum. A novel cytochrome cd1 with Fe(II):nitrite oxidoreductase
      activity.
AB  - Cytochrome cd1 nitrite reductase was isolated from magnetite-containing cells of
      the magnetotactic bacterium Magnetospirillum (formerly Aquaspirillum)
      magnetotacticum, which was microaerobically cultivated under denitrifying
      conditions. The enzyme showed absorption maxima at 643 nm and 409 nm in the
      oxidized form, and at 663, 551, 522, and 418 nm in the reduced form. A
      distinctive split absorption band did not occur at about 550 nm. The pyridine
      ferrohemochrome spectra suggested the presence of heme c and heme d1 in the
      molecule. The enzyme was composed of two identical subunits each with a molecular
      mass of 54 kDa; each subunit contained one c-type and one d-type heme. The
      isoelectric point was 9.2. The redox potentials of heme c and heme d1 were
      estimated to be +191 mV and +180 mV, respectively. Although the enzyme showed
      cyanide-sensitive N,N,N',N'-tetramethyl-p-phenylenediamine-O2 oxidoreductase
      activity and N,N,N',N'-tetramethyl-p-phenylenediamine-nitrite oxidoreductase
      activity, the enzyme did not oxidize M. magnetotacticum ferrocytochrome c-550 and
      Pseudomonas aeruginosa ferrocytochrome c-551 in the presence of nitrite.
      Furthermore, sodium succinate did not cause the reduction of cytochrome cd1 in
      the crude cell-free extract prepared from the magnetite-containing bacterial
      cells. However, M. magnetotacticum cytochrome cd1 showed a novel Fe(II):nitrite
      oxidoreductase activity whereas P. aeruginosa cytochromes cd1 had no
      Fe(II):nitrite oxidoreductase activity. These results suggest that M.
      magnetotacticum cytochrome cd1 may function as a Fe(II)-oxidizing enzyme under
      microaerobic conditions using nitrite as electron acceptor.

PMID- 7588815
TI  - NMR studies of the action of hypochlorous acid on native pig articular cartilage.
AB  - The action of sodium hypochlorite on pig articular cartilage was studied by 1H
      NMR spectroscopy to model some aspects of degradation processes of cartilage
      during rheumatoid arthritis. Two effects of NaOCl on cartilage polysaccharides
      have been observed. Hypochlorous acid causes an enhanced release of oligomeric
      polysaccharides from cartilage. The second effect concerns the degradation of N
      acetyl side chains of carbohydrates to acetate via a chlorinated transient
      product. Signal intensities for N-acetyl groups (approximately 2.0 ppm) increase
      during the first 2 h of incubation of cartilage with NaOCl. Then they decrease
      again. However, acetate (1.90 ppm) as the final product of degradation of N
      acetyl side chains increases continuously over the period of incubation with
      NaOCl. In addition to polysaccharides, effects of NaOCl were only observed in
      cartilage samples on amino acids like alanine. The alanine resonance disappeared
      already at NaOCl concentrations where only small effects on cartilage
      polysaccharides have been observed.

PMID- 7588812
TI  - Solution characterisation by NMR spectroscopy of two horseradish peroxidase
      isoenzyme C mutants with alanine replacing either Phe142 or Phe143.
AB  - Site-directed mutagenesis of the horseradish peroxidase isoenzyme C (HRP C) gene
      has been undertaken in order to provide two recombinant enzymes where alanine
      replaces either Phe142 or Phe143 ([F142A]HRP C and [F143A]HRP C, respectively).
      These heme enzymes have been characterised in solution using proton NMR
      spectroscopy for both the high-spin resting and low-spin cyanide-ligated states.
      Comparison of their NMR spectra with those recorded for wild-type plant HRP C
      indicates that both the protein fold and the structure of the heme pocket are
      maintained. The structural integrity of the aromatic donor molecule binding site
      is altered as a result of the substitution of Phe142 by Ala, but not by the
      corresponding substitution at Phe143. This is evident from analysis of
      perturbations to the chemical shift and linewidth parameters of the proton
      resonances of two Phe side chains, Phe A and Phe B, that participate in this
      site. The resting and cyanide-ligated states of [F142A]HRP C bind the aromatic
      donor molecule, benzhydroxamic acid, three to four times more weakly than the
      analogous states of wild-type plant HRP C. A titration of cyanide-ligated
      [F142A]HRP C with benzhydroxamic acid, monitored by NMR spectroscopy, further
      reveals that the dynamics of complex formation are considerably altered, in that
      only one of the two possible benzhydroxamic acid binding modes established for
      the cyanide-ligated wild-type enzyme is significantly populated. Although the
      assignment of Phe A and Phe B cannot be made to either Phe142 or Phe143, the
      results confirm that Phe142 is an important, although indirect, determinant of
      aromatic donor molecular binding and dynamics. The role of phenylalanine side
      chains in the binding of aromatic donor molecules by heme peroxidases is
      discussed in the light of these observations and a recent structural model for
      HRP C.

PMID- 7588816
TI  - Functional and structural changes of the photosystem II complex induced by high
      irradiance in cyanobacterial cells.
AB  - A gradual disintegration of the photosystem II (PSII) complex, initiated by a
      release of the chlorophyll-protein CP43, was identified during low-temperature
      illumination of Synechococcus cells. This process was slower compared to the
      decline of the PSII primary charge separation activity, and much slower than the
      photoinactivation of oxygen evolution. All three processes were slowed down in
      the presence of diuron. The results indicate that when the PSII repair was
      blocked, the inactivation of charge separation activity and the release of CP43
      preceded the degradation of the D1 protein. In contrast, a much faster
      degradation of D1 connected to its rapid exchange was triggered by inactivation
      of oxygen evolution, and no disassembly of PSII was needed. We propose the
      existence of two different mechanisms of D1 degradation in the cells of the
      thermophilic cyanobacterium Synechococcus elongatus.

PMID- 7588817
TI  - Complete amino acid sequence of a zinc metalloendoprotease from Streptomyces
      caespitosus.
AB  - We determined the complete amino acid sequence of a zinc metalloendoprotease from
      Streptomyces caespitosus (ScNP). Peptide fragments obtained by digestion of Rcm
      ScNP with trypsin, ScNP and endoproteinase Asp-N were purified by reverse-phase
      HPLC and their amino acids were analyzed using an automatic sequencer. ScNP
      consisted of a single polypeptide chain of 132 amino acid residues with one
      disulfide bond between residues 99 and 112 (M(r) 14376). Thus, the number of
      amino acid residues determined for this enzyme is much lower than the number of
      residues previously reported for metalloendoproteases. The amino acid sequence
      indicated that although ScNP has the zinc-binding motif. His-Glu-Xaa-Xaa-His,
      which is found at the active site of most zinc metalloendoproteases, it does not
      share overall significant similarity to the sequences of other zinc
      metalloendoproteases. Moreover, an analysis of the X-ray structure of ScNP at 0.2
      nm resolution (Kirisu et al., unpublished results) revealed that Asp93, together
      with two histidine residues in the zinc-binding motif (His83 and His87) and a
      water molecule, is a zinc ligand. We propose that ScNP, which bears the
      HEXXHXXGXXD motif, represents a novel subfamily of zinc-containing
      metalloendoproteases.

PMID- 7588818
TI  - The uniform galactose 4-sulfate structure in the carbohydrate-protein linkage
      region of human urinary trypsin inhibitor.
AB  - The carbohydrate-protein linkage region of a chondroitin 4-sulfate chain attached
      to urinary trypsin inhibitor (UTI) was isolated from human urine and
      characterized structurally. The chondroitin 4-sulfate chain was released from UTI
      by beta-elimination using alkaline NaBH4 then digested with chondroitinase ABC.
      These treatments resulted in only a single hexasaccharide alditol derived from
      the carbohydrate-protein linkage region. Chemical and enzymic analyses and 600
      MHz 1H-NMR spectroscopy revealed that the hexasaccharide alditol had the
      following structure: delta HexA alpha 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-
      3Gal(4-sulfate) beta 1-3Gal beta 1-4Xyl-ol, where delta HexA, GlcA and Xyl-ol
      represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, D-glucuronic acid
      and D-xylitol, respectively. This structure contained the novel 4-sulfated Gal
      residue, which was first demonstrated in one of the three linkage hexasaccharide
      serines isolated from chondroitin 4-sulfate of rat chondrosarcoma [Sugahara, K.,
      Yamashina, I., de Waard, P., Van Halbeek, H. & Vliegenhart, J. F. G. (1988) J.
      Biol. Chem. 263, 10168-10174]. This disulfated structure was recently identified
      as the sole structural component in the linkage hexasaccharide alditol fraction
      isolated from inter-alpha-trypsin inhibitor (ITI) in human plasma [Yamada, S.,
      Oyama, M., Kinugasa, H., Nakagawa, T., Kawasaki, T., Nagasawa, S., Khoo, K.-H.,
      Morris, H.R., Dell, A. & Sugahara, K. (1995) Glycobiology 5, 335-341]. The
      structural uniformity in the linkage hexasaccharide structure of ITI and UTI is
      in marked contrast to the heterogeneity demonstrated in the linkage
      hexasaccharides isolated from cartilaginous chondroitin sulfate whose linkage
      regions are sometimes but not always phosphorylated on the Xyl residue or
      sulfated on the Gal residue(s). The uniform structure containing the novel 4
      sulfated Gal residue in the linkage region of UTI and ITI may imply its
      significance in the biosynthetic mechanism of chondroitin sulfate.

PMID- 7588819
TI  - Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with
      antibacterial and antifungal properties.
AB  - One of the characteristics of the host defense of higher insects is the rapid and
      transient synthesis of a variety of potent antimicrobial peptides. To date,
      several distinct inducible antimicrobial peptides or peptide families have been
      totally or partially characterized. We present here the isolation and
      characterization of a novel 26-residue proline-rich immune-inducible peptide from
      Drosophila, which exhibits both antibacterial (Gram-positive) and antifungal
      activities. Peptide sequencing and cDNA cloning indicate the presense of two
      isoforms in our Drosophila Oregon strain, which differ by one residue (His
      compared to Arg) as a consequence of a single nucleotide change. The gene, which
      maps in position 52A1-2 on the right arm of the second chromosome, is expressed
      in the fat body after immune challenge. The novel peptide, which we propose to
      name metchnikowin, is a member of a family of proline-rich peptides, and we
      discuss the possible evolutionary relationships within this family.

PMID- 7588820
TI  - Pneumococcal virulence factors and host immune responses to them.
AB  - The principal virulence determinant of most encapsulated bacterial pathogens is
      the possession of an extracellular capsule. This paper discusses biological
      aspects of the Streptococcus pneumoniae capsule, putative roles played by
      accessory virulence factors of this pathogen and prospects for improvement of the
      currently available pneumococcal vaccine. Even though the interruption of genes
      encoding selected proteins has been shown to attenuate virulence to some degree,
      the physical removal of the pneumococcal capsule or the interruption of
      encapsulation genes completely abolishes virulence in mice. The role of the
      capsule in pathogenesis is not completely clear, however, since it is not known
      whether this structure is important in colonization, the obligatory first step in
      the process. In addition, a number of proteins have been implicated as possible
      accessory virulence factors. These include pneumolysin, two distinct
      neuraminidases, an IgA1 protease and two surface proteins, pspA and psaA. While
      interruption of the expression of some of these proteins examined to date has
      been shown to attenuate virulence, so far it has not proven possible to
      completely abolish virulence in this fashion. Proteinaceous accessory virulence
      factors may prove important to the development of second-generation pneumococcal
      vaccines, however. Pneumococcal and other proteins conjugated to pneumococcal
      polysaccharides are currently being evaluated as carriers in attempts to improve
      the immunogenicity of polysaccharide vaccines, primarily in small children.

PMID- 7588821
TI  - Molecular analysis by pulsed-field gel electrophoresis of penicillin-resistant
      Streptococcus pneumoniae from Toulouse, France.
AB  - A sample of 28 penicillin-resistant Streptococcus pneumoniae strains isolated
      between 1991 and 1993 in a large hospital in Toulouse, France, was characterized
      by pulsed-field gel electrophoresis of genomic DNA. Also included were 6
      penicillin-susceptible clinical isolates from Toulouse and 12 penicillin
      resistant strains from different parts of the world. The restriction
      endonucleases ApaI and SmaI were used to digest intact chromosomes, and the
      fragments were resolved by field-inversion gel electrophoresis. Seven major
      pattern types could be recognized among the penicillin-resistant isolates from
      Toulouse. Nine of these isolates could be assigned to two clones that were also
      found in Spain and were associated with serotypes 6B and 9V. A third clone was
      isolated in South Africa and in Spain and contained serotype 23F isolates. The
      profiles obtained by field-inversion gel electrophoresis suggested that 15 of the
      16 penicillin-resistant serogroup 23 isolates from Toulouse belonged to the same
      Spanish 23F clone. The molecular test profiles of penicillin-susceptible strains
      differed from those of resistant strains of the same serotype except those of 9V
      strains. These data underline the importance of the geographic spread of
      resistant clones from Spain in the emergence of penicillin-resistant pneumococci
      in France.

PMID- 7588822
TI  - Role of antigenemia assay in the early diagnosis and prediction of human
      cytomegalovirus organ involvement in AIDS patients.
AB  - The role of an antigenemia assay in the diagnosis and prediction of human
      cytomegalovirus (HCMV) disease in AIDS patients was evaluated. The clinical
      history of 62 patients with advanced HIV infection from whom a total of 248 blood
      samples were drawn and tested by the HCMV antigenemia assay was examined
      retrospectively. Between December 1992 and January 1994, 28 episodes of HCMV
      disease with organ involvement were recorded; the antigenemia assay was positive
      in 23 of them (82.1%). In particular, this test was positive in 11 of 12 (91.6%)
      first episodes and in 3 of 3 (100%) recurrent episodes occurring in patients not
      receiving maintenance therapy. The same test was positive in 9 of 13 (69.2%)
      recurrent episodes occurring in patients receiving maintenance therapy. The first
      occurrence of HCMV disease was always preceded by a positive antigenemia assay 2
      and 4 months before diagnosis (in all 7 patients of the 7 for whom a blood sample
      was available before HCMV disease). A positive antigenemia test result was not
      always followed by organ involvement, but a high positive cell count (>
      100/200,000 polymorphonuclear leukocytes) strongly correlated with the appearance
      of HCMV disease in the following 1 to 3 months (100% of cases). The antigenemia
      assay is a useful and reliable indirect method for the diagnosis and prediction
      of HCMV end-organ disease in severely and persistently immunocompromised AIDS
      patients.

PMID- 7588823
TI  - Longitudinal study of cytomegalovirus antibodies in individuals infected with the
      human immunodeficiency virus.
AB  - Cytomegalovirus (CMV) antibody profiles were studied in 25 HIV-infected patients
      over periods of up to 56 months. Specific antibodies against CMV antigen
      components were monitored by complement-fixation (CF) test, EIA, Western blot and
      a neutralization assay. Three subjects remained CMV seronegative throughout the
      study. Marked fluctuations were observed in anti-CMV antibodies assayed by the CF
      test as compared to a control group. Fluctuations on immunoblots of purified
      virion antigens were also observed in the HIV-infected patients; neutralizing
      antibodies and anti-CMV nucleocapsid antibodies showed less variability. Seven of
      22 individuals exhibited an increase in CF-test titre of up to 64-fold without
      clinically apparent CMV disease. On Western-blot testing of IgG reactivity with
      disrupted virions, ten individuals exhibited increasing reactivity to pp65, and
      only three of these also showed a titre rise in the CF test. In contrast, 7 of 22
      showed low reactivity to the pp28 antigen. The homosexual patient group exhibited
      the highest levels of anti-CMV antibody. In conclusion, many asymptomatic HIV
      infected subjects showed fluctuations at different levels of their antibody
      response to CMV, thought to be indicative of CMV reactivation/reinfection.
      Western-blot findings indicated that some CMV antibodies increased in level while
      others were lost.

PMID- 7588824
TI  - Emergence and clinical relevance of mutations associated with zidovudine
      resistance in asymptomatic HIV-1 infected patients.
AB  - The dynamics leading to the emergence of a zidovudine-resistant mutation at codon
      215 of the reverse transcriptase coding region was investigated in a cohort of
      HIV-infected individuals who received early zidovudine therapy. Clinical
      implications and the role of the resistance mutation at codon 41 were also
      assessed. Thirty-eight initially asymptomatic HIV-infected patients with a CD4+
      cell count above 400 cells/mm3 were followed for a mean period of 121 weeks (20
      received zidovudine and 18 matching placebo). Specific mutations in the HIV-1
      reverse transcriptase coding region conferring resistance to zidovudine were
      detected using a selective polymerase chain reaction. During the follow-up period
      a mutation at codon 215 was detected in eight (40%) of the individuals in the
      zidovudine group, and in two of these eight subjects, a mutation at codon 41 was
      found. During the study, disease progression occurred in seven of the eight (88%)
      patients with a mutation at codon 215, compared with 7 of 18 (39%) patients
      assigned to the placebo group and 3 of the 12 (25%) patients receiving zidovudine
      treatment who did not develop a 215-mutant strain (p < 0.05). At entry, none of
      the patients harbored MT-2 tropic virus. Therefore, the emergence of a zidovudine
      resistant mutation at codon 215 is associated with subsequent disease progression
      in asymptomatic HIV-infected patients who receive zidovudine monotherapy. This
      association suggests that the mutation at codon 215 is involved in a loss of
      therapeutic efficacy and, therefore, patients should be monitored during
      treatment with zidovudine.

PMID- 7588825
TI  - Capnocytophaga canimorsus septicemia: fifth report of a cat-associated infection
      and five other cases.
AB  - Capnocytophaga canimorsus is a fastidious, slow-growing, gram-negative, rod
      shaped bacterium that belongs to the normal oral flora of dogs and cats. Human
      septicemic infections are associated with a high mortality; most cases occur in
      immunocompromised patients with a history of dog bite. The fifth case of cat
      associated septicemia caused by Capnocytophaga canimorsus is described. The six
      case reports presented here point out the characteristics reported previously:
      (a) cats are a source of human infection; (b) alcohol abuse is an important risk
      factor for the development of septicemic Capnocytophaga canimorsus infection; (c)
      septicemic infection often manifests with disseminated intravascular consumption
      coagulopathy or purpura; and (d) some cases of septicemia in humans result from
      pets that lick skin ulcers.

PMID- 7588827
TI  - Recurrent Streptococcus pneumoniae endocarditis.
AB  - A case of recurrent endocarditis due to Streptococcus pneumoniae, a rare cause of
      endocarditis, is reported. The first episode of infection resulted in valvular
      damage, necessitating replacement of the aortic and mitral valves, and the second
      episode was treated successfully with antibiotics alone. Recurrence occurred even
      though the organism was fully susceptible to the antibiotics used and the patient
      showed no evidence of immune deficiency.

PMID- 7588826
TI  - Catheter-related cutaneous aspergillosis complicated by fungemia and fatal
      pulmonary infection in an HIV-positive patient with acute lymphocytic leukemia.
AB  - A case of intravenous catheter-related cutaneous aspergillosis and Aspergillus
      fumigatus fungemia in an HIV-positive patient with Burkitt-cell acute lymphocytic
      leukemia is reported. The patient developed pulmonary aspergillosis with a
      rapidly fatal outcome despite recovery from neutropenia and improvement of the
      underlying malignancy. The unusual severity and rapid spread of the infection,
      despite normal neutrophil count and prompt antifungal therapy, suggest that HIV
      related immunocompromise might play a role in the impairment of host defences
      against Aspergillus infection. Thus catheter-related cutaneous aspergillosis
      could lead to a severe deep-seated infection in HIV-positive patients.

PMID- 7588828
TI  - Capsular types and antimicrobial resistance of Streptococcus pneumoniae isolated
      in Korea.
AB  - The capsular types and the MICs of penicillin G and other antimicrobial agents
      were determined for 89 isolates of Streptococcus pneumoniae. MICs of penicillin G
      ranged from 0.015 to 2 mg/l, with 29% and 48% of the isolates exhibiting
      intermediate resistance and complete resistance, respectively. All isolates were
      susceptible to teicoplanin and vancomycin, but 81% and 43% of the penicillin G
      resistant strains were intermediately resistant to cefotaxime and imipenem,
      respectively. Strains belonged to 16 different capsular types: 73% belonged to
      types 19F and 23F, and 97% of strains belonging to these two types exhibited
      either intermediate or complete resistance to penicillin G.

PMID- 7588830
TI  - Combined effect of human neutrophils, ceftazidime and granulocyte colony
      stimulating factor on killing of Escherichia coli.
AB  - The combination effect of subinhibitory and inhibitory concentrations of
      ceftazidime, granulocyte colony-stimulating factor (G-CSF) and polymorphonuclear
      leukocytes (PMNL) against Escherichia coli was investigated. PMNL obtained from
      healthy volunteers were incubated with different concentrations of G-CSF and
      ceftazidime for 180 min. The addition of 0.25 x MIC of ceftazidime or 1 x MIC
      significantly enhanced the bactericidal activity of PMNL. G-CSF at a
      concentration of 6,000 units/ml led to only a slight improvement in the
      bactericidal activity of PMNL. The combination of 6,000 units/ml G-CSF and
      ceftazidime in inhibitory as well as subinhibitory concentrations, however,
      showed a significant synergistic effect (p < 0.01) on the antibacterial activity
      of PMNL during the entire incubation period. Combinations of G-CSF and
      antibiotics could therefore be beneficial for infected patients, especially those
      with impaired cellular host defence.

PMID- 7588831
TI  - Comparison of two selective media and a membrane filter technique for isolation
      of Campylobacter species from diarrhoeal stools.
AB  - Diarrhoeal stool specimens from 415 patients were examined for Campylobacter spp.
      by culture on charcoal cefoperazone deoxycholate agar (CCDA), Skirrow medium and
      Columbia blood agar overlaid with a 0.65 micron pore size membrane filter. Forty
      eight Campylobacter strains were isolated from 45 (10.8%) specimens by all media;
      44 were Campylobacter jejuni (91.7%), three were Campylobacter coli (6.3%) and
      one was Campylobacter hyointestinalis (2.0%). The percentages of Campylobacter
      positive specimens isolated on Skirrow medium, CCDA and the membrane filter were
      62, 82 and 95%, respectively. The recovery of more Campylobacter spp. from the
      same stool sample was achieved by the membrane filter method only. The highest
      isolation rate (100%) was observed when culture on CCDA and the membrane filter
      method were combined.

PMID- 7588829
TI  - Easier monitoring of aminoglycoside therapy with once-daily dosing schedules.
AB  - Little has been reported on serum levels attained using once-daily aminoglycoside
      regimens and their relation to dosage administered and renal function.
      Consecutive patients with serious infections were randomized to receive
      gentamicin 4 mg/kg q 24h i.v. (n = 69), gentamicin 1.33 mg/kg q 8h i.v. (n = 46)
      or netilmicin 5.5 mg/kg q 24h i.v. (n = 59) (with dose reduction in case of renal
      dysfunction). In the three groups, median first serum trough levels were 0.4, 1.0
      and 0.4 mg/l, respectively, and median first serum peak levels were 9.5, 4.7 and
      12.2 mg/l (p < 0.01 once-daily vs. thrice-daily regimens). Dose adjustment
      because of first trough concentrations of > 2 mg/l and/or peak concentrations of
      < 6 mg/l was required in 6%, 78% and 12% of patients, respectively. Second trough
      and peak concentrations were significantly higher in the thrice-daily gentamicin
      group; serum levels remained constant in the other two groups. The six patients
      in the once-daily groups who developed elevated trough levels later in therapy
      were characterized in most cases by a decline in renal function.

PMID- 7588832
TI  - Three-year study of antibody to Borrelia burgdorferi in southern Spain.
AB  - The prevalence of anti-Borrelia burgdorferi antibodies was studied in Granada,
      Spain, between January 1991 and November 1993 in 354 patients with suspected Lyme
      disease (group 1); in 50 patients either with syphilis (n = 32) or without
      syphilis but with a positive Rapid Plasma Reagin test (n = 18) (group 2); and in
      150 healthy subjects (group 3). In addition, intrathecal antibody production was
      evaluated by EIA in CSF samples obtained from 117 patients in group 1. Anti
      Borrelia burgdorferi antibodies were detected by EIA in 58 patients (16.4%) in
      group 1, 29 (8.2%) of whom were positive by Western blot. Intrathecal antibody
      production was detected in one patient. In group 2, 8 (16%) patients had a
      positive EIA result, but none of these was confirmed by Western blot. western
      blot was negative for all subjects in group 3. The results of this study indicate
      that anti-Borrelia burgdorferi antibodies are not uncommon in our area, although
      Lyme disease is rare.

PMID- 7588833
TI  - Comparison of enzyme immunoassay antigen detection, nucleic acid hybridization
      and PCR assay in the diagnosis of Chlamydia trachomatis infection.
AB  - An enzyme immunoassay (EIA) antigen detection system (MicroTrak, Syva), nucleic
      acid hybridization (PACE 2, Gen-Probe) and polymerase chain reaction (PCR) assay
      (Amplicor, Hoffmann-La Roche) were evaluated for the detection of Chlamydia
      trachomatis in a high-risk female population. Of 234 specimens, 42 (18%) were
      positive. The respective sensitivity of the EIA, RNA hybridization and the PCR
      was 81, 90 and 88%. When additionally performed on diluted specimens, PCR gave
      positive results for three of four PCR-negative specimens from EIA- and RNA
      hybridization-positive women and a sensitivity of 95%. Thus, both techniques
      employing gene technology offered a clear improvement in sensitivity over the
      EIA. Future improvements in the PCR should be directed towards the elimination of
      polymerase inhibition.

PMID- 7588834
TI  - Use of a commercial PCR kit for detection of hepatitis C virus.
AB  - To evaluate the usefulness of a recently developed standardised reverse
      transcription polymerase chain reaction (PCR) kit for detection of hepatitis C
      virus RNA (Amplicor HCV Test, Roche Molecular Systems), a total of 322 serum
      samples were examined and compared to an in-house nested PCR. Seventy-nine
      samples were found positive and 237 samples negative by both methods. Five sera
      were reactive by the commercial test only, and one was reactive by the nested PCR
      only. It was concluded that the commercial HCV test had comparable sensitivity
      and specificity to the in-house nested PCR. However, the commercial HCV test was
      more rapid and easier to perform than nested PCR and is thus more appropriate for
      use in a diagnostic microbiology laboratory.

PMID- 7588835
TI  - Patterns of recovery phase infection after autologous blood progenitor cell
      transplantation in patients with malignancies. The Gruppo Italiano di Studio per
      la Manipolazione Cellulare in Ematologia.
AB  - Recovery phase infection patterns in 55 patients who had undergone autologous
      blood progenitor cell transplantation (ABPCT) were evaluated retrospectively. The
      results were compared to those obtained in a group of 41 patients who received
      autologous bone marrow transplantation (ABMT). Fever related to documented or
      suspected infection developed in 38 of 55 patients in the ABPCT group and in 37
      of 41 in the ABMT group (p < 0.05). The percentages of patients with positive
      blood cultures did not differ significantly (ABPCT, 8/55 vs. ABMT, 8/41, p >
      0.05). However, fewer acquired systemic fungal infections (1/55 vs. 5/41, p <
      0.05) as well as fewer days of antibiotic usage were observed in the ABPCT group.

PMID- 7588836
TI  - Endocarditis due to Streptococcus oralis in a patient with a colon tumour.

PMID- 7588837
TI  - Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection.

PMID- 7588838
TI  - Fluconazole in the treatment of three cases of mucormycosis.

PMID- 7588839
TI  - Olecranon bursitis due to Prototheca wickerhamii, an algal opportunistic
      pathogen.

PMID- 7588841
TI  - Microparticle agglutination versus antibody-capture enzyme immunoassay for
      diagnosis of community-acquired Mycoplasma pneumoniae pneumonia.
AB  - Community-acquired Mycoplasma pneumoniae pneumonia is a common disease which is
      usually diagnosed by serological methods. The objective of the present study was
      to understand the diagnostic significance and test characteristics of two
      different serological tests used to identify current Mycoplasma pneumoniae
      infection. Three hundred sixty-six patients who suffered from community-acquired
      pneumonia served as the study population. Six hundred ninety-four (328 paired and
      38 unpaired) sera were examined for the presence of antibodies to Mycoplasma
      pneumoniae with commercial kits based on two serological methods, microparticle
      agglutination and antibody-capture EIA. Agreement between the two kits was 85.2%
      when individual sera were compared (kappa = 0.62) and 88.5% when patients were
      compared (Kappa = 0.69). The positive predictive value and the specificity for
      the identification of current Mycoplasma pneumoniae infection using a single
      acute-phase serum were 49.3% and 86.9%, respectively, for the microparticle
      agglutination method, compared to 91.3% and 97.7% for the antibody-capture EIA
      method (p < 0.001). The negative predictive value and the sensitivity were 86.3%
      and 48.1% for the microparticle agglutination, not significantly different from
      the corresponding values of 86.5% and 61.2% for the antibody-capture EIA. It is
      concluded that the overall agreement between the two methods tested is good, but
      not perfect. The methods complement each other in the identification of
      Mycoplasma pneumoniae as the causative agent in patients with community-acquired
      pneumonia.

PMID- 7588840
TI  - Risk factors for nosocomial colonization with multiresistant Acinetobacter
      baumannii.
AB  - A six-month prospective survey was carried out in a university hospital to assess
      the incidence of Acinetobacter baumannii cross-contamination and to identify risk
      factors for colonization. Clinical isolates obtained during the study period were
      biotyped and genotyped by pulsed-field gel electrophoresis after ApaI
      macrorestriction of total DNA. Case-control univariate and multivariate analyses
      were performed to identify risk factors for Acinetobacter baumannii colonization.
      One hundred forty-seven patients hospitalized in 36 units were colonized or
      infected, of whom 52 were in three intensive care units. The urinary (29%) and
      bronchopulmonary tracts (26%) were the most frequently colonized sites. Nine
      major restriction patterns were identified: two were exhibited by epidemic multi
      resistant strains of biotype 9 which were isolated from 65 patients hospitalized
      in ten units. Multivariate analysis showed that case-patients were (a) more
      likely than non-infected controls to be male, to have been previously
      hospitalized in another unit and to have had longer stays in the unit before
      colonization and hyperalimentation; and (b) more likely than controls colonized
      with other gram-negative bacilli to be male, to have had longer hospitalization,
      to have received treatment with third-generation cephalosporins and to have had a
      urinary catheter. The high incidence of colonization with Acinetobacter baumannii
      can thus be attributed to frequent cross-contamination and the use of broad
      spectrum antibiotics. Colonized patients appear to be the major source of cross
      contamination as epidemic strains spread throughout the hospital.

PMID- 7588844
TI  - Sternotomy infection due to Mycoplasma hominis and Ureaplasma urealyticum.
AB  - Mycoplasma hominis infections outside the urogenital tract are uncommon. An
      unusual case of sternal infection caused by both Mycoplasma hominis and
      Ureaplasma urealyticum is described. This is the first report found in the
      literature of mixed infection due to these microorganisms at this site. The
      outcome was favourable after drainage of the surgical wound and antibiotic
      therapy with clindamycin, gentamicin and doxycycline.

PMID- 7588846
TI  - Fatal meningoencephalitis caused by Scedosporium inflatum (Scedosporium
      prolificans) in a child with lymphoblastic leukemia.
AB  - A fatal case of meningoencephalitis caused by Scedosporium inflatum (Scedosporium
      prolificans) in a 5-year-old boy with acute myeloblastic leukemia who was given
      intrathecal treatment is reported. Itraconazole treatment was ineffective. The
      fungus was identified on brain sections at autopsy and was not observed in any
      other organ. As no other portal of entry was detected, meningoencephalitis may
      have originated via direct introduction of the fungus at therapeutic lumbar
      puncture.

PMID- 7588845
TI  - Chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to
      Clostridium difficile.
AB  - A case of chronic septic arthritis and osteomyelitis in a prosthetic knee joint
      due to Clostridium difficile is reported. A knee prosthesis was installed in a 16
      year-old boy for surgical treatment of an osteosarcoma of the femur. Later, the
      patient suffered a traumatic closed fracture of his patella, and a sterile fluid
      was aspirated. One month later, the joint displayed inflammation. Culture of the
      articular fluid yielded a nontoxigenic Clostridium difficile strain. Despite
      several attempts using conservative medical treatment with penicillins and
      ornidazole, Clostridium difficile strains with the same antibiotic susceptibility
      pattern were repeatedly isolated from the joint over an eight-month period. The
      foreign material was then ablated, and finally, the patient's leg was amputated
      one year after Clostridium difficile was first isolated. The possible sources of
      contamination in our case and other reported cases of extraintestinal infection
      due to Clostridium difficile are discussed.

PMID- 7588843
TI  - Association between HIV and other DNA viruses in vitro.
AB  - To investigate the association of human immunodeficiency virus (HIV) with various
      DNA viruses, including hepatitis B virus (HBV), cytomegalovirus (CMV) and Epstein
      Barr virus, (EBV), simultaneous detection of HIV p24 antigen, HBV surface antigen
      and DNA, CMV-DNA and EBV-DNA expression was performed in phytohemagglutinin
      stimulated peripheral blood mononuclear (PBMC) culture supernatants obtained from
      54 individuals at risk for HIV infection. HIV expression in PBMC culture
      supernatants never occurred alone; expression of other viruses was always
      detected in the 24 samples expressing HIV antigen in vitro. Furthermore, in 16
      patients expression of other viruses was detected without HIV expression, and in
      14 patients none of the tested viruses were detected. These results indicate a
      strong association between the presence of HIV antibody and expression of DNA
      viruses in vitro (p = 0.0001). The coexpression of these viruses could be related
      to the evolution of HIV infection and AIDS.

PMID- 7588842
TI  - Value of specific immunoglobulin A detection by two immunocapture assays in the
      diagnosis of toxoplasmosis.
AB  - The diagnosis of Toxoplasma gondii infection is currently based on immunological
      tests, but tests for IgG and IgM antibodies alone are often insufficient to
      assess the risk of active disease, especially during pregnancy and in
      immunodeficient subjects. The supplementary diagnostic value of testing for
      antitoxoplasmic IgA in cases of acute, chronic, congenital and reactivated
      toxoplasmosis, relative to classical immunological tests, was evaluated using two
      immunocapture tests, one based on tachyzoite agglutination and the other on an
      immunoenzymatic complex recognizing the membrane protein P30 of Toxoplasma
      gondii. A total of 4,541 sera from 395 uninfected subjects, 468 immunized
      subjects with chronic infection, 117 subjects with acute infection and 403
      children, 103 of whom had congenital toxoplasmosis, was tested. Specific IgA
      tests were negative in the nonimmune population, but tests for this
      immunoglobulin subtype became positive very rapidly during primary infection, and
      IgA disappeared more rapidly than IgM. In the children infected in utero,
      specific IgA was detected more frequently than IgM. In contrast, in a population
      of HIV-seropositive subjects with clinical toxoplasmosis, tests for IgA were
      poorly sensitive. The two tests for specific IgA produced similar results, except
      in the early stages of primary infection, in which immunoenzymatic testing for
      anti-P30 IgA was less sensitive than the agglutination method.

PMID- 7588847
TI  - Relationship between iron status and recrudescent herpes labialis.
AB  - A prospective study was undertaken to assess the relationship between
      recrudescent herpes labialis and host iron status. Forty-one patients with
      recrudescent herpes labialis, proven by herpes simplex virus isolation, were
      studied along with an equal number of age-and-sex matched control subjects. The
      iron status of patients and controls were assessed by haematine assay of
      ferritin. The iron (ferritin) level in patients with recrudescent herpes labialis
      was significantly (p < 0.01) lower than in the control group. Only one patient
      was anaemic. Side-ropenia appears to be a common finding in patients with
      recrudescent herpes labialis. The relationship between sideropenia and
      recrudescent herpes labialis requires further study as it may have implications
      for the management of the disease.

PMID- 7588848
TI  - Evaluation of a new dipslide with a selective medium for the rapid detection of
      beta-glucuronidase-positive Escherichia coli.
AB  - A selective medium was incorporated into a new three-media dipslide (Uricult
      Trio, Orion Diagnostica) to allow rapid identification of Escherichia coli. The
      medium is supplemented with a recently described chromogenic substrate,
      hydroxyquinoline-beta-D-glucuronide, for beta-glucuronidase enzyme. The
      performance of the medium was compared to that of three other beta-glucuronidase
      detection methods in tests of 602 routine urine samples. Of 324 Escherichia coli
      strains isolated, 92% grew brown colonies on dipslide, thus being beta
      glucuronidase positive. The proportion of beta-glucuronidase-positive Escherichia
      coli detected by the three methods was 93% for BGA II agar plates (Tammer-Tutka),
      91% for PGUA tablets (Rosco) and 84% for Fluorocult Brolacin agar plates (Merck).
      No false-positive reactions were seen in the case of 209 significant isolates of
      species other than Escherichia coli grown on the selective medium.

PMID- 7588849
TI  - Evaluation of a Lyme disease enzyme immunoassay using the 41-G fragment of
      flagellin.
AB  - An immunogenic region of the Borrelia burgdorferi flagellin encompassing amino
      acids 197-273 and designated 41-G was evaluated as an antigen in an enzyme
      immunoassay (EIA) for Lyme disease on a routine basis in a reference laboratory.
      Sera that tested positive for Lyme disease by EIA using 41-G or the whole-cell
      Borrelia burgdorferi lysate as the antigen were also evaluated by immunoblot for
      reactivity with Borrelia burgdorferi, and the patient's clinical history was
      determined retrospectively by a questionnaire distributed to the referring
      physician. The sensitivity of the 41-G based EIA for the serologic diagnosis of
      Lyme disease, when compared with that of the Borrelia burgdorferi lysate EIA, was
      70% (35 of 50). These data demonstrate that 41-G has utility as an antigen in
      EIA, although the sensitivity is at present less than that of the assay employing
      the Borrelia burgdorferi whole-cell lysate.

PMID- 7588850
TI  - Pathogenicity and antifungal susceptibility of Chaetomium species.
AB  - Several reports have been published implicating Chaetomium spp. as opportunistic
      pathogens. A critical review of these cases was made, and the majority of the
      responsible strains were studied. Chaetomium globosum was the most common
      species, being isolated in at least nine clinical cases of infection. Some of
      these clinical isolates and others from environmental sources were tested against
      six antifungal agents (5-fluorocytosine, fluconazole, amphotericin B,
      itraconazole, ketoconazole and miconazole). The 23 strains tested were totally
      resistant to the first two drugs, and none of the other antifungal agents
      demonstrated fungicidal activity. There were no significant differences between
      the susceptibility of the clinical strains and the other strains.

PMID- 7588851
TI  - Detection of pathogenic fungi in human blood by the polymerase chain reaction.
AB  - The ability of the polymerase chain reaction (PCR) to detect pathogenic fungi in
      human blood was investigated. A DNA fragment of about 300 bp from the 18S rDNA,
      highly conserved in all fungi, was amplified with target DNA from 18 different
      species of fungi commonly isolated from clinical samples. The presence of PCR
      products was confirmed by hybridization with a fluorescein-labelled internal
      probe (21-mer). The PCR assay described is sensitive enough to detect 125 fg of
      purified Candida albicans DNA and 10 to 100 yeast cells per millilitre of blood.

PMID- 7588854
TI  - Molecular basis for cross-reactivity between a strain of Mycobacterium terrae and
      DNA probes for Mycobacterium tuberculosis complex.

PMID- 7588853
TI  - Native valve endocarditis due to nutritionally variant Streptococcus adjacens
      associated with Enterococcus faecium.

PMID- 7588852
TI  - Detection of HIV-1 proviral sequences in lymphocytes using a qualitative
      polymerase chain reaction assay.
AB  - The performance and clinical relevance of a qualitative PCR-based assay for the
      detection of HIV-1 DNA sequences in peripheral blood mononuclear cells (PBMCs)
      was evaluated by two different laboratories. Four hundred and one samples were
      obtained from 397 individuals from different risk populations. All blood donors
      tested had negative results; positive signals were obtained from all infected
      patients. HIV-1 DNA was detected in 3 of 17 infants born to seropositive mothers;
      Western blot indeterminate blood donors and exposed health-care workers had
      negative results. Our results demonstrate that this PCR assay provides both
      sensitive and specific results and is suitable for testing large numbers of
      samples and for rapid identification of HIV-1 infection.

PMID- 7588855
TI  - Comparison of two PCR-based assays for detecting Mycoplasma genitalium in
      clinical specimens.

PMID- 7588856
TI  - Hepatitis C virus seroconversion in a hemophiliac treated exclusively with
      solvent/detergent-treated clotting factor concentrate.

PMID- 7588857
TI  - Antibiotic selection factors and description of a hospital-based outpatient
      antibiotic therapy program in the USA.
AB  - A variety of pharmacodynamic, pharmacokinetic and drug stability factors can
      influence the choice of drug, the dosing regimen and the method of drug
      administration for out-patient parenteral antibiotic therapy (OPAT). Beta-lactam
      antibiotics exhibit little if any concentration-dependent killing and produce
      short-term or no persistent effects with most bacterial pathogens. Optimal dosing
      regimens for these agents should provide serum levels that continually exceed the
      minimal inhibitory concentration (MIC) of the pathogen. Beta-lactam agents with
      long half-lives (greater than 2 hours) can provide these levels with intermittent
      dosing once or twice daily. Beta-lactam agents with shorter half-lives can be
      administered by programmable pumps or by continuous infusion providing the drug
      is sufficiently stable to degradation in solution. Imipenem and ampicillin are
      examples of drugs with short half-lives that are unstable in solution and must be
      dosed intermittently. Intramuscular administration slows absorption and can also
      prolong the length of time during which serum levels exceed the MIC of infecting
      bacteria. Aminoglycosides and fluoroquinolones, on the other hand, exhibit
      concentration-dependent killing and produce prolonged persistent effects. Optimal
      dosage regimens of these drugs should maximize serum levels. Once-daily dosing
      regimens for the aminoglycosides meet this goal and also appear to reduce drug
      induced nephrotoxicity. Application of these principles to drug selection and
      administration in a hospital-based OPAT program has provided efficacious therapy
      and a low incidence of adverse reactions in an elderly population distributed
      over a wide geographic area.

PMID- 7588858
TI  - Experience with outpatient intravenous teicoplanin therapy for chronic
      osteomyelitis.
AB  - Thirty-seven patients with acute exacerbations of chronic osteomyelitis caused by
      methicillin-susceptible Staphylococcus aureus (n = 13), methicillin-resistant
      Staphylococcus aureus (n = 12), methicillin-susceptible coagulase-negative
      staphylococci (n = 9), methicillin-resistant coagulase-negative staphylococci (n
      = 1) and enterococci (n = 2) were treated intravenously with teicoplanin. After a
      loading dose of 7 to 16 mg/kg (median 11 mg/kg) for 4 to 7 days, patients
      received 9 to 25 mg/kg (median 14 mg/kg) on Mondays, Wednesdays and Fridays in an
      outpatient setting to reach trough serum levels between 5 mg/l and 15 mg/l. The
      duration of treatment ranged from 28 to 150 days (median 60 days). Cure was
      obtained in 14 (38%) and improvement in 17 (46%) cases, and failure was observed
      in 6 (16%) patients. Adverse effects occurred in 6 patients, and caused
      discontinuation of treatment in 3 patients. The financial savings exceeded
      US$60,000 per patient compared with the high hospitalization costs of inpatient
      treatment.

PMID- 7588861
TI  - Congenital absence of the neural arch in the cervical spine: an extreme form of
      pedicle absence.

PMID- 7588859
TI  - Outpatient treatment of endocarditis in a clinic-based program in Argentina.
AB  - The major cost in the treatment of infective endocarditis (IE) is the length of
      hospitalization required for the administration of intravenous antibiotics. This
      can be reduced by substituting shorter regimens and by the introduction of
      outpatient parenteral antibiotic therapy (OPAT). Careful selection of patients is
      vital for the success of OPAT in IE. The patients should be hemodynamically
      stable and without clinical complications. The delivery of OPAT for IE followed a
      clinical and home-based program involving an endocarditis team whose members
      included an infectious diseases physician, a microbiologist, a cardiologist and a
      nurse trained in intravenous techniques. Among the antimicrobial agents used in
      OPAT of IE, single-agent ceftriaxone for four weeks followed by a short course of
      amoxicillin or ceftriaxone in combination with an aminoglycoside for two weeks
      (short course) are effective modes of treatment for streptococcal endocarditis,
      the most common cause of IE. This treatment is also effective for carefully
      selected patients with other types of endocarditis, such as those due to the
      HACEK group (Haemophilus aphrophilus/paraphrophilis, Actinobacillus actinomycetem
      comitans, Caradiobacterium hominis, Eikenella corrodens and Kingella kingae).
      Staphylococcus aureus, enterococci and late prosthetic valve endocarditis
      associated with a streptococcus may also be treated on an outpatient basis after
      stabilization (approximately 2 weeks). As a result of their need for prolonged
      treatment periods, these patients are also very good candidates for OPAT. In
      conclusion, new regimens utilizing ceftriaxone once daily and short-term therapy
      on a clinical or home basis offer the potential benefits of cheaper safer and
      more convenient treatment for patients with IE.

PMID- 7588860
TI  - Experience with a physician-directed, clinic-based program for outpatient
      parenteral antibiotic therapy in the USA.
AB  - The experience with 538 patients who received outpatient parenteral antibiotic
      therapy (OPAT) in 1993 in a private institute in Tacoma, Washington, USA, is
      reviewed here. Clinical outcomes suggested a successful resolution of infection
      in 99% of cases. Bacteriological outcomes showed that eradication of the organism
      had occurred in 92% of patients by the end of therapy. The success of the program
      indicates that 91% of properly selected patients can be treated without adverse
      events. Antibiotics were changed in 45 (8%) instances, but only half of these
      changes were made because of an adverse event. The development of rash was the
      most frequent adverse event and resulted in hospitalization in only 1 instance.
      Hospitalization was necessary before the OPAT program was completed in 42 cases-
      20 of those were for surgery and 13 for medical reasons unrelated to the
      infection or antibiotic therapy. In 8 cases, patients were hospitalized because
      of failure of home care or inability to administer the antibiotics effectively.
      Three patients were taken off the program because of failure to comply. Patient
      satisfaction surveys suggested that 99% of patients were satisfied with the
      program. With careful patient selection and a well-developed program, OPAT can be
      safe, effective and beneficial to patients and can save costs in healthcare
      services.

PMID- 7588862
TI  - A brachiocephalic vein abnormality causing a 'twisted' central venous catheter.

PMID- 7588863
TI  - Central venous catheter-related thrombosis in clinically asymptomatic oncologic
      patients: a phlebographic study.
AB  - Fifty-seven oncologic patients with short- or long-term central venous catheters
      (CVCs) and without clinical signs of axillary-subclavian thrombosis were
      evaluated phlebographically. Different degrees of incomplete thrombosis were
      found in 26 patients (45.5%) and complete thrombosis, clinically silent, was
      found in six patients (10.5%). A fibrin sleeve around the CVC was radiologically
      demonstrated in 45 (78%) patients, 21 of them (46%) with negative standard
      venogram. Only in four patients there was no evidence of fibrin sleeve or
      parietal thrombosis. There were no significant differences between patients with
      long-term and short-term CVCs. We conclude that parietal thrombosis of the
      axillary-subclavian veins is a frequent event, even if there is no clinical
      evidence of flow obstruction and we confirm in vivo that a fibrin coating of the
      CVCs is present in the majority of the cases.

PMID- 7588864
TI  - The 'pinch-off phenomenon': a radiological symptom for potential fracture of an
      implanted permanent subclavian catheter system.

PMID- 7588868
TI  - Ultrasound and Doppler in the diagnosis of ovarian torsion.

PMID- 7588867
TI  - Automatic left ventricular volume measurements on contrast-enhanced ultrafast
      cine magnetic resonance imaging.
AB  - To assess the accuracy of automatic extraction of the left ventricular inner
      contour on contrast-enhanced ultrafast cine magnetic resonance (MR) images, we
      compared the values obtained by this method with those obtained using intravenous
      digital subtraction left ventriculography. High-quality single breath-hold
      contrast-enhanced ultrafast cine MR images were obtained in all cardiac phases on
      horizontal and vertical long axis sections of the left ventricle. For ultrafast
      cine MR imaging, a phase-rewind gradient-echo (rewind-SMASH) sequence was used.
      Automatic extraction of the left ventricular inner contour on contrast-enhanced
      ultrafast cine MR images was performed in all cardiac phases. High-quality left
      ventricular images of the horizontal long axis section were obtained in 127 of
      160 patients (79%). The automatic extraction of the left ventricular contour was
      easily performed on high-quality images with very short processing time (4
      s/frame). The values for left ventricular volumes obtained with the automatic
      extraction method on contrast-enhanced ultrafast cine MR imaging were correlated
      well with those obtained with the manual extraction method and IV-DSA in high
      quality cardiac images. The biplane modified Simpson's method using automatic
      extraction is an accurate and highly reproducible method for evaluating left
      ventricular volumes.

PMID- 7588866
TI  - Unusually located osteoid osteomas.
AB  - The files of 12 patients (aged 12-33 years) with an equal number of surgically
      proven osteoid osteomas (OOs) were reviewed in attempt to find a diagnostic
      algorithm in cases of unusually located OOs. Plain radiography (PR) and thin
      collimation computed tomography (CT) had been performed in all patients, while
      bone scintigraphy (BS) had been performed in eight and magnetic resonance imaging
      (MRI) in two. The OOs were located at juxta- or intra-articular sites, except for
      one located at the left neck of the L4 vertebra. The diagnosis based on the MRI
      examinations was synovitis. BS showed increased accumulation of the radioisotope
      at the site of the lesions, without the 'double density' sign. PR showed the
      nidus of OO in only six patients, whereas CT located the nidus in all patients.
      In conclusion, we believe that when an OO is clinically suspected at an unusual
      location, CT should be performed in all cases, even when a lesion is depicted by
      PR and BS, because CT will not only locate the nidus but will also provide a
      precise anatomy of the area around the nidus and help in therapeutic decision
      making and surgical planning. MRI can be misleading and must not be used in the
      initial assessment of a possible osteoid osteoma.

PMID- 7588869
TI  - Mature cystic teratomas of the ovary: CT and MR findings.
AB  - OBJECTIVE: To correlate CT and MR patterns of ovarian mature cystic teratomas
      (MCT). SUBJECTS AND METHODS: CT and MR findings in 25 histologically proven
      ovarian MCT were retrospectively reviewed. MCT characterization at CT and MR was
      based on detection of fat and/or a Rokitansky protuberance. MR signal intensity
      and CT density numbers of fat were correlated. RESULTS: At pathology, 24/25
      tumors contained fat, 1/25 a water content, and 23/25 a Rokitansky protuberance.
      Twenty one MCT contained fat with a density number less than-20 HU (mean density:
      -95 HU) and a signal intensity superior or equal to sub-cutaneous fat on T1
      images, however, only six of these had a signal intensity equal to sub-cutaneous
      fat on T1 and T2 images and 12 had a reversed chemical shift artifact. Three
      contained fat with a density number ranging from -13 to +8 HU and a signal
      intensity inferior to subcutaneous fat on T1 images. CT showed a Rokitansky
      protuberance in 21/23, containing adipose tissue in 16 and calcified structures
      in 21. Standard MR showed a Rokitansky protuberance in 14/23 and characterized
      adipose tissue in eight cases, and calcified material in six cases. Finally, CT
      characterized 24/25 (96%) MCT. Standard MR characterized 22/25 (88%) MCT, and
      standard MR with fat-suppression sequences characterized 23/25 (92%) MCT.
      CONCLUSION: Standard MR is less effective than CT in characterizing fat and has
      the same difficulty as CT in characterizing fat mixed with hair when its density
      is high. When fat cannot be identified by either technique, diagnosis of a
      Rokitansky protuberance is more easily made at CT than at MR.

PMID- 7588872
TI  - Comparison of low-field versus high-field MR imaging.

PMID- 7588870
TI  - Angiographic properties of Gd-DTPA-24-cascade-polymer--a new macromolecular MR
      contrast agent.
AB  - PURPOSE: A new macromolecular MR contrast agent, Gd-DTPA-24-cascade-polymer, was
      assessed for MR angiography of peritumoral vessels in rats. MATERIAL AND METHODS:
      High resolution 3D-SPGR (TR/TE 100/5ms, alpha = 90 degrees) angiograms were
      acquired in 10 Fischer rats bearing subcutaneous R3230 mammary adenocarcinomas.
      MRI was performed before, immediately and 40 min after administration of Gd-DTPA
      (0.1 mmol Gd/kg), and after either Gd-DTPA-cascade-polymer or albumin-(Gd-DTPA)30
      (each 0.05 mmol Gd/kg). A semi-quantitative analysis of small peritumoral vessels
      and tumor rim enhancement was performed on maximum intensity projection (MIP)
      angiograms using a 4-point scoring system. A quantitative analysis compared
      vascular signal-to-background-(S/B), signal-to-noise-, and contrast-to-noise
      ratio. RESULTS: Gd-DTPA produced a transient and low-scoring vessel definition
      (0.2 +/- 0.1), but strong rim enhancement (score 1.7 +/- 0.1). The cascade
      polymer resulted in better but submaximal vessel delineation (score 1.6 +/- 0.3,
      S/B 5.0 +/- 0.2) and strong rim enhancement (score 1.8 +/- 0.1). Albumin-(Gd
      DTPA)30 produced the best and most time-persistent angiograms (score 2.6 +/- 0.2,
      S/B 7.4 +/- 0.2), but minimal rim enhancement (score 0.3 +/- 0.2). CONCLUSIONS:
      The Gd-DTPA-24-cascade-polymer demonstrated the useful combination of strong
      tumor rim enhancement and detailed angiographic definition of peritumoral
      vessels. These are advantages associated with extracellular and blood pool
      contrast media, respectively.

PMID- 7588871
TI  - Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals.
AB  - We report the computed tomographic appearance of invasive fungal disease of the
      paranasal sinuses in 13 patients. Coronal and axial computed tomographic images
      were obtained in each patient and data were analysed. Eight patients had
      Aspergillus flavus infection, four had Mucormycosis, and one had mixed Candida
      and Mucor. Our experience was different from that of other workers in many
      respects. All of our patients were immunocompetent. On radiological imaging by
      computed tomography, ethmoid sinuses were involved in 85% of our patients. In
      previously reported series maxillary sinuses were most frequently affected.
      Calcification in the inflammatory mass was not encountered in any of our
      patients, whereas this feature was present in many reported cases. Features in
      our patients that were similar to other studies were contrast enhancement,
      extension of the disease into the orbit and cranial cavity and a high mortality.
      The clinical course and radiological features of invasive mycosis simulate
      malignancy. Certain features that may help to differentiate invasive fungal
      infection from malignancy are discussed. We conclude that invasive fungal
      infection can affect immunocompetent individuals and should be considered in the
      differential diagnosis in appropriate clinical settings.

PMID- 7588865
TI  - Low-dose and conventional-dose high resolution CT of pulmonary changes in breast
      cancer patients treated by tangential field radiotherapy.
AB  - Twenty-seven consecutive breast cancer patients receiving tangential field
      radiation therapy were followed by high resolution CT (HRCT) in order to compare
      the accuracy of reduced-dose HRCT and conventional-dose HRCT in the evaluation of
      subtle pulmonary changes. Thin section 1-mm HRCT images were obtained at
      identical levels at 120 kVp, with 320 mAs, 200 mAs, 160 mAs, 120 mAs and 60 mAs
      settings. HRCT was performed during the planning of radiotherapy and 4, 8 and 24
      weeks after the completion of radiotherapy. Radiation was administered according
      to an individual CT-based plan by tangential fields with 4 or 6 MV photons to the
      whole breast given with 5 fractions of 1.9 Gy weekly to a total dose of 50 Gy.
      The tumor bed was boosted by electrons to 60 Gy. Pathological changes were
      detected in 21 examinations of 10 patients: 9 patients out of 27 (33%) showed
      radiation induced changes; 1 patient developed metastases within the irradiated
      volume. Septal thickening appeared in 5 patients at 4 weeks and in another 5
      patients at 8 weeks. Parenchymal consolidation was detected in 1 patient at 4
      weeks and in 5 patients at 8 weeks. HRCT using 160 mAs yield good quality images
      of subtle radiation induced injuries. The diagnostic validity of HRCT using lower
      than 160 mAs depends on the detail analyzed.

PMID- 7588873
TI  - The European Spine Phantom--a tool for standardization and quality control in
      spinal bone mineral measurements by DXA and QCT.
AB  - The lack of standardization in bone mineral measurements of the lumbar spine and
      other skeletal sites is generally recognized as an important and unresolved
      issue. We report and discuss efforts at standardization and cross-calibration of
      DXA and QCT equipment. We have designed and tested a geometrically defined, semi
      anthropomorphic phantom, the European Spine Phantom (ESP). It contains a spine
      insert consisting of three vertebrae of increasing bone mineral densities and
      thicknesses of cortical structures; the respective parameters are given in
      tabular form for the final phantom design. Results for cross-calibration with the
      ESP compare well with patient results. Measurements on the first 30 phantoms
      confirmed that the ESP can be manufactured with a variation of about 1%. We
      conclude that the ESP is suitable for daily quality assurance, cross-calibration
      of instruments and universal standardization. The ESP was used to establish
      standardized BMD (sBMD) units for DXA equipment going into effect in late 1995.
      Its acceptance by manufacturers as a calibration standard for DXA and QCT
      measurements appears imminent.

PMID- 7588874
TI  - MR of leptomeningeal melanosis in children.
AB  - PURPOSE: To delineate the magnetic resonance (MR) appearance of leptomeningeal
      melanosis in children. METHOD: Retrospective review of the medical, surgical,
      pathologic and MR findings in four children with a confirmed histologic diagnosis
      of leptomeningeal melanosis. The brain MR was performed with T1- and T2-weighted
      images in all four children and three had T1-weighted post-gadolinium images. Two
      of the children also had T1-weighted post gadolinium spine images. RESULTS: The
      MR brain findings consisted of cortical plaque and nodular hyperintense lesions
      on the noncontrast T1-weighted images in one child, marked, diffuse
      leptomeningeal enhancement in two children, and an enlarged, hypointense left
      temporal lobe with adjacent mild leptomeningeal enhancement in one child. The MR
      spine findings consisted of diffuse leptomeningeal enhancement in one child and
      hyperintensity of the cerebrospinal fluid in the other. CONCLUSION: The T1
      weighted pre- and post-contrast images were the best to demonstrate the MR
      findings in leptomeningeal melanosis which consisted of either diffuse or
      localized enhancement of the leptomeninges; or cortical plaque and nodular
      hyperintense lesions pre-contrast.

PMID- 7588875
TI  - Differential expression of the microspike-associated protein moesin in human
      tissues.
AB  - The protein moesin is a member of a gene family consisting of talin, ezrin,
      radixin, protein 4.1., and merlin. Proteins of this family are associated to the
      submenbranous cytoskeleton. Using monoclonal antibody 38/87 directed against
      moesin in immunochemical analysis, the 78 kDa moesin protein was demonstrated in
      endothelial cells and in cells of carcinoma, mesothelioma and lymphoid origin.
      Moesin was metabolically labeled by [32P]orthophosphate and reacted with an
      antibody against phosphotyrosine. Moesin also contains carbohydrate residues as
      demonstrated by immunostainings of digoxigenin-labeled sugar residues. The
      antibody 38/87 in comparison to antisera against radixin and ezrin was applied in
      immunohistological stainings on various human tissues. As a prominent feature,
      moesin as strongly expressed in endothelium of vessels in contrast to radixin and
      ezrin. Moesin but not radixin was observed in T and B lymphocytes. Further,
      moesin was expressed in basal layers of squamous epithelium and glandular ducts
      and lymphocytes. Subcellular expression of moesin was studied on cultured human
      endothelial cells of umbilical cord veins and the mesothelioma cell line CH3LC by
      confocal laser scanning microscopy. In subconfluently growing cells moesin showed
      a characteristic expression on extending microspikes at the basal cell level.
      Moesin was coexpressed with actin in the cortical cytoskeleton and on microspikes
      but not in stress fibers. The differential cellular expression of moesin and its
      pronounced occurrence on microspikes of growing cells support the possibility
      that moesin is a protein involved in plasma membrane-cytoskeleton interactions in
      specialized tissues.

PMID- 7588878
TI  - Two strategies to prepare neural cortical cytoskeleton components for the
      generation of monoclonal antibodies.
AB  - Like most other cells, neurons possess a spectrin/actin based network closely
      associated with the inner side of the cell membrane, the cortical cytoskeleton.
      This structure serves many diverse functions during axonal outgrowth. In the
      growth cone, the cortical cytoskeleton is involved in surface shaping, modulation
      of integral membrane proteins, and signal transduction. We developed two
      strategies to prepare material enriched for neural cortical cytoskeleton. The
      first strategy combined the isolation of a membrane/cortical cytoskeleton
      fraction by density gradient centrifugation with an enzymatic degradation of cell
      surface proteins. The second strategy is based on the attachment and crosslinking
      of single cells to beads, allowing for the removal of the cell contents by cell
      disruption; only membrane/cortical cytoskeleton patches are retained on the
      beads. Both strategies made use of the intimate association of the cortical
      cytoskeleton with the cell membrane, permitting the removal of cytoplasm,
      organelles and cytoplasmic cytoskeleton while retaining the cortical
      cytoskeleton. Monoclonal antibodies generated using both preparations as
      immunization material were screened for recognition of intracellular structures
      in axons and growth cones of retinal ganglion cells in culture. A quantitative
      specification of the antibodies is presented and six antibodies are characterized
      in immunolabelings and Western blot analysis.

PMID- 7588877
TI  - Confocal imaging and immunogold electron microscopy of changes in distribution of
      myosin during pollen hydration, germination and pollen tube growth in Nicotiana
      tabacum L.
AB  - Using anti-myosin antibodies, standard immunocytochemical techniques in
      conjunction with confocal scanning laser microscopy and colloidal gold
      immunoelectron microscopy we compare changes in the distribution patterns of
      myosin during the early stages of pollen hydration, germination, tube growth, and
      myosin associated with isolated vegetative nucleus and the generative cell in
      Nicotiana tabacum L. Furthermore, on the Western blots of pollen tube proteins,
      the antimyosin antibodies crossreact only with one polypeptide of approximately
      174 kDa. Confocal immunofluorescence microscopy reveals that in hydrated pollen,
      myosin is discretely associated with the cytoplasmic organelles and numerous
      punctate structures present in the center of the pollen. Within 30 min following
      transfer of pollen into the germination medium, that is, with the onset of
      germination, the centrally located punctate structures are displaced, and we find
      accumulation of myosin-associated organelles towards one of the germinal
      apertures from which the pollen tube would emerge. Subsequently, after 45 min of
      germination with the emergence of germination structure, few punctate structures
      are detected in the vegetative cytoplasm while intense immunostain is detected
      just below the plasma membrane of the emerging pollen tube tip. In the older
      parts of both short and long pollen tubes after 90 to 120 min of pollen
      germination, few fluorescent structures were found in the pollen tubes, however,
      numerous punctate fluorescent spots were concentrated in the tip region over a
      distance of 2 to 3 microns below the plasma membrane of the tube tip. This is
      further substantiated by colloidal gold immunoelectron microscopy wherein
      clusters of gold particles are associated with vesicle-like structures in the tip
      region of the pollen tubes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588879
TI  - Effect of microtubule network disturbance by nocodazole and docetaxel (Taxotere)
      on protein secretion in rat extraorbital lacrimal and parotid glands.
AB  - The role of microtubules in the exocrine secretory process is not yet well
      established. Contradictory effects of anti-microtubule drugs on intracellular
      transit and protein secretion have been reported. In this work we used
      microscopic techniques and pulse-chase experiments to compare the involvement of
      microtubules in the regulated secretory process of two rat exocrine glands:
      parotid and extraorbital lacrimal glands. In our experiments microtubules were
      either disrupted by nocodazole or stabilized by a taxoid, docetaxel (Taxotere).
      We show that the effect of nocodazole and docetaxel on the release of newly
      synthesized proteins is radically different in the two tissues; in parotid gland
      they only weakly affect protein release, triggered by stimulation of either
      muscarinic or beta-adrenergic receptors, but in lacrimal gland, they strongly
      inhibit protein secretion. This effect or lack of effect of the drug is
      independent of the signal transduction pathways involved by the different
      secretagogues used to trigger exocytosis. Furthermore, in lacrimal glands,
      studies on protein galactosylation (which occurs in the trans-Golgi compartment)
      indicate that postgalactosylation events are more sensitive to both drugs than
      pregalactosylation events. On the other hand, we show that the effect of
      nocodazole and docetaxel on the microtubule network is comparable on the two
      tissues. Finally, in lacrimal cells, we observed a scattering of the Golgi
      apparatus concomitant with the disruption of microtubules by nocodazole. We
      conclude from this study that microtubule network integrity is essential for
      protein secretion in lacrimal glands but not in parotid glands. This result
      implies that for the same physiological function, i.e. protein secretion,
      different mechanisms may be involved.

PMID- 7588881
TI  - Stable expression of acetylcholinesterase and associated collagenic subunits in
      transfected RBL cell lines: production of GPI-anchored dimers and collagen-tailed
      forms.
AB  - We obtained a stable expression of acetylcholinesterase (AChE, E.C. 3.1.1.7) in
      the rat basoleukemia cell line, RBL-2H3, which possesses a well developed
      secretory pathway, but expresses only very little endogenous AChE. Metabolic
      labeling showed that AChEH and AChET, differing by C-terminal peptides encoded by
      alternatively spliced exons, were synthesized at a similar rate. When transfected
      with AChEH, RBL cells efficiently produced GPI-anchored dimers, which were mostly
      exposed at the cell surface, as shown both by activity and immunofluorescence
      labeling. In contrast, when transfected with AChET, RBL cells produced about
      tenfold less activity, which was essentially retained in the cell, and the enzyme
      could not be detected at the cell surface by immunolabeling. The fate of the
      enzyme is therefore determined by its C-terminal alternative peptides. We were
      also able to coexpress the AChET subunit with the collagenic Q subunit. The cells
      produced small but significant amounts of collagen-tailed forms, essentially A4.
      The expression of these different catalytic and structural subunits in stably
      transfected RBL cells will be useful to explore the regulated posttranslational
      processes involved in protein maturation and transport.

PMID- 7588876
TI  - The nuclear membrane-associated honeycomb structure of the unicellular organism
      Amoeba proteus: on the search for homologies with the nuclear lamina of metazoa.
AB  - In the protozoon Amoeba proteus, a complex and highly organized structure with
      the morphology of a honeycomb is associated with the nucleoplasmic surface of the
      nuclear membrane. We have tested whether this structure exhibits similarity to
      the nuclear lamina of metazoic organisms. First, we have shown that the honeycomb
      layer is composed of 3 to 5 nm thick protein fibrils resistant to treatment with
      detergent, high salt, and digestion with nucleases, thus possessing properties
      typical for karyoskeletal elements. However, in contrast to the meshwork of lamin
      filaments in somatic cells of metazoic organisms, the honeycomb layer is not
      tightly anchored to the nucleoplasmic side of pore complexes, or to the inner
      nuclear membrane. Second, in microinjection experiments we investigated whether
      fluorescently labeled lamins of Xenopus laevis (lamins A and LI) and Drosophila
      melanogaster (lamin Dmo) were able to associate in vivo with the Amoeba proteus
      honeycomb structure. In microinjected amoeba these three lamins were efficiently
      transported into the nucleus, but did not associate with the nuclear envelope.
      Our results suggest that the Amoeba proteus nuclear envelope, including the
      honeycomb layer, does not contain proteins exhibiting high homologies to lamins
      of metazoan species thus preventing the localized assembly of microinjected
      lamins along the nuclear periphery.

PMID- 7588882
TI  - The sulfation degree of membrane-associated proteoglycan from a hemopoietic cell
      line is determined by changes in the growth state of the cell.
AB  - Multipotential hemopoietic progenitor cells (FDCP-mix) proliferate in culture
      medium supplemented with horse serum. When transferred to a medium without serum,
      cells do not proliferate and enter a quiescent state. Both proliferative and
      quiescent cells synthesize only chondroitin sulfate proteoglycan (CS-PG) which is
      associated to the cell membrane. Incorporation of 35SO4 into CS-PG was 4-fold
      higher in quiescent than in proliferative cells. Flow cytometric studies using
      monoclonal antibodies which recognize the core protein or the CS chains, showed
      that the increased uptake of sulfate was not the consequence of an increase in
      the abundance of CS-PG. Further characterization demonstrated that CS-PG isolated
      from quiescent cells exhibited a slightly higher hydrodynamic size than CS-PG
      from proliferative cells. However, the glycosaminoglycan chains from PG derived
      from proliferative and quiescent cells have the same hydrodynamic size. Through
      ion-exchange chromatography we observed that the mean charge density of PG from
      quiescent cells was higher than in proliferative cells, suggesting a higher
      sulfation degree from PG synthesized by quiescent cells. This was confirmed by
      flow cytometric studies using monoclonal antibody 2B6, which recognizes the
      unsaturated terminal disaccharide of chondroitin-4-O-sulfate.

PMID- 7588880
TI  - Filensin is proteolytically processed during lens fiber cell differentiation by
      multiple independent pathways.
AB  - Filensin is a lens-specific intermediate filament protein, expressed in the lens
      fiber cells but not the lens epithelium. Using antibodies to filensin and the
      other lens intermediate filament proteins, vimentin and CP49, the codistribution
      of filensin with CP49 and independence of this network from the vimentin network
      was confirmed. Monoclonal and polyclonal antibodies to peptides and specific
      subdomains of filensin were used to follow changes in the subcellular
      distribution of filensin during bovine lens fiber cell differentiation. Filensin
      is shown to be extensively processed during lens fiber cell differentiation to
      give protein fragments derived from distinct protein domains, one corresponding
      to the N-terminal non-alpha-helical/and rod domain and the other to the C
      terminal non-alpha-helical tail domain. Immunoblotting analysis using anti
      filensin peptide polyclonal antibodies suggested that the two fragment sets arose
      separately. Residues 331 to 430 in filensin have been identified as an important
      region in the processing pathway(s). Our results clarify previous confusion in
      the literature regarding the processing of filensin which arose because of the
      similar relative electrophoretic mobilities by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) of the different fragment sets. The
      predicted secondary structure characteristics of the different domains of
      filensin suggests different functions for the two fragment sets to give filensin
      a dual role in the lens. This suggestion is supported by the subtly different
      subcellular distributions in the peripheral and mature fiber cells of the two
      filensin fragment sets.

PMID- 7588883
TI  - Effect of ATP depletion and DTT on the transport of membrane proteins from the
      endoplasmic reticulum and the intermediate compartment to the Golgi complex.
AB  - Newly synthesized membrane proteins are exported from the endoplasmic reticulum
      to the Golgi complex through an intermediate compartment. Incubation at low
      temperature (15 degrees C) arrests the proteins in the intermediate compartment
      and prevents the entry into the Golgi complex. We have studied, in living cells,
      the effect of dithiothreitol (DTT) and ATP depletion on the transport to the
      Golgi complex of proteins accumulated either in the endoplasmic reticulum or in
      the intermediate compartment after a temperature block. The morphological results
      obtained with vesicular stomatitis virus ts-O45 G glycoprotein and the
      biochemical analysis performed with human CD8 protein, an O-glycosylated protein,
      showed that: 1) ATP depletion blocks the export to the Golgi complex of proteins
      located either in the endoplasmic reticulum or in the intermediate compartment
      and ii) DTT interferes with the folding and export of proteins located in the
      endoplasmic reticulum, but it does not prevent the transfer from the intermediate
      compartment to the Golgi complex.

PMID- 7588884
TI  - Rop and Ras2, members of the Sec1 and Ras families, are localized in the outer
      membranes of labyrinthine channels and vesicles of Drosophila nephrocyte, the
      Garland cell.
AB  - The product of the ras opposite (rop) gene is an essential component of secretion
      processes in Drosophila. The rop gene product is homologous to the Caenorhabditis
      elegans UNC-18 and the rat munc-18/n-Sec1/rbSec1 proteins, implicated in the
      final steps of neurotransmitter exocytosis in nerve terminals, and the bovine
      mSec1 protein implicated in the secretion of catecholamines in chromaffin cells.
      The mammalian brain protein has been shown to exert its activity in the
      presynaptic membrane through transient interaction with syntaxin, an integral
      component of this membrane. rop is highly expressed in the Drosophila nervous
      system, where it acts as both a positive and negative modulator of
      neurotransmitter release. It is also expressed in specialized tissues in which
      intensive exocytic/endocytic cycles take place, including the garland cells, a
      small group of nephrocytes which take up waste materials from the hemolymph by
      endocytosis. rop is regulated by a bidirectional promoter shared with Ras2, a
      member of the R-ras/TC21 branch of the ras supergene family. Ras2 is also highly
      expressed in the garland cells. These cells are characterized by their
      labyrinthine channels, long invaginations extending from the cell membrane, and a
      rich population of a variety of vesicles. In this study, we analyzed the
      ultrastructural localization of the Rop and Ras2 proteins in the garland cell.
      Rop was detected in the outer membranes of the labyrinthine channels, and in the
      outer membranes of many vesicles located nearby the labyrinthine channels, but
      not in vesicles located in inner parts of the cell. Using glutathione-S
      transferase-syntaxin fusion, we show that Rop is firmly bound to
      syntaxin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588885
TI  - Percutaneous arterial approach revisited.

PMID- 7588887
TI  - Do we still need to count premature ventricular contractions?

PMID- 7588888
TI  - Aspects of the aetiology of congenital heart disease.
AB  - A concise overview of current knowledge on the aetiology of congenital heart
      disease is provided. At present, only 10 to 20% of the cases occurring in
      neonates can be attributed to known risk factors. Recurrence within relatives,
      chromosomal anomalies, genetic disorders, maternal disease and teratogen exposure
      are addressed briefly; contemporary research models and methods, e.g. embryology
      and genetics and molecular biology, are referred to. A major innovation has been
      the introduction of the concept of common pathogenetic pathways. Thus, different
      teratogenic factors or risk-factors may affect normal development at an identical
      stage and cause similar malformations. Also, the importance of timing of an event
      is stressed. If the time frame of exposure does not coincide with embryogenesis
      any teratogenic effect may be missed. Large-scale epidemiological studies on
      fetuses and neonates with congenital heart disease are introduced as a third mode
      of research on the aetiology, although this approach is not used efficiently at
      present; cases of intra-uterine death can be considered a valuable source of
      information that needs further attention. Combined, the above three lines of
      research may prove productive, but the design of a comprehensive research project
      would need to be handled carefully. Possibilities for prevention of the
      occurrence of cardiovascular malformations are reported. Through lack of
      knowledge of causality, at present, only secondary prevention may be possible and
      hence deserves attention. However, there appears to be no provision for thorough
      pre-natal screening tests for congenital heart disease in an unselected
      population.

PMID- 7588891
TI  - Syndrome X in women is associated with oestrogen deficiency.
AB  - This study was undertaken to ascertain whether gynaecological history or a
      reduction in ovarian hormones are triggers of angina in menopausal women with a
      positive exercise test and normal coronary arteries. The majority of patients
      with angina pectoris, a positive exercise test and normal coronary arteries are
      female, suggesting that the female gender may be important in the aetiology. We
      studied the gynaecological features of 107 women (age 53 +/- 9 years) with
      syndrome X, taken from a population of 134 patients including 27 males.
      Cardiological investigations were undertaken and detailed gynaecological history
      obtained from all the female patients. Menopausal status was confirmed by plasma
      levels of oestradiol-17 beta < or = 100 pmol.l-1. In 95 of the 107 female
      patients, chest pain began either during the perimenopausal period (32) or after
      the menopause (63). Of the 63 menopausal patients, 43 had undergone hysterectomy
      at an average of 8 +/- 6 years prior to the onset of chest pain. The incidence of
      hysterectomy in the study population (40%) was four times greater than that of an
      age-matched population. These findings confirm that the majority of patients with
      syndrome X are women in whom the chest pain began after the onset of menopause.
      Ovarian hormone deficiency may, therefore, play a role in the onset of syndrome X
      in female patients.

PMID- 7588889
TI  - Identification of high-risk subgroups in infective endocarditis and the role of
      echocardiography.
AB  - The outcome of infective endocarditis remains poor. It has an overall mortality
      of around 30%, rising in high-risk subgroups to 50% and 100%. The prognosis can
      be improved by identification of high-risk patients and special management.
      Patients with infective endocarditis are found to be at high risk for death or
      serious complications when one or more of the following factors exist: old age
      (especially > 60 years old), delayed diagnosis, staphylococcal infection, aortic
      valve endocarditis, large valvular vegetation, congestive heart failure,
      embolization in the central nervous system or coronary artery, prosthetic valve
      infection, recurrent events, and failed antibiotic therapy. These factors often
      coexist and interrelate with one another. Early diagnosis and active treatment
      are critical for a better clinical outcome. However, infective endocarditis is
      difficult to diagnose because of the atypical clinical manifestations and
      frequent negative results from blood culture. Echocardiography plays an
      indispensable role in the diagnosis and management of suspected or known
      infective endocarditis. By detecting and monitoring certain pathological changes
      associated with the disease, e.g. vegetation, abscess formation, or valvular
      destruction, echocardiography helps to diagnose the disease early, to identify
      patients at high risk, to monitor the patients, and to optimize the timing and
      mode of surgical intervention. Serious complications can thus be avoided or cured
      at an early stage and the prognosis significantly improved.

PMID- 7588890
TI  - Comparative study on the effects of intracoronary nicorandil and nitroglycerin in
      ischaemic, reperfused porcine hearts.
AB  - The direct cardioprotective properties of nitroglycerin and nicorandil were
      compared in regionally ischaemic (45 min), reperfused (24 h) porcine hearts.
      Intracoronary treatments, which were started 15 min prior to occlusion of the
      distal left anterior descending coronary artery (LAD), were continuously
      administered for 105 min. The following equi-hypotensive drug dosages were used
      in nine pigs each; nitroglycerin 6 micrograms.kg-1 x min before ischaemia and
      during 45 min of reperfusion, 0.6 microgram.kg-1 x min during ischaemia;
      nicorandil 5 micrograms.kg-1 x min before ischaemia and during 45 min of
      reperfusion, and 0.5 microgram.kg-1 x min during ischaemia. Nine control animals
      were treated with isotonic sodium hydrochloride solution (1 ml.min-1). Despite
      comparable effects on blood pressure, intracoronary nicorandil, in contrast to
      intracoronary nitroglycerin, did not increase heart rate. Although neither drug
      affected coronary blood flow significantly, nicorandil substantially reduced
      regional myocardial oxygen consumption before coronary artery occlusion (-37 +/-
      22%, P = 0.003 vs control group, P = 0.01 vs nitroglycerin treatment). Infarct
      sizes (tetrazolium method) after 45 min of ischaemia and 24 h of reperfusion were
      significantly decreased by nicorandil (control group 76.9 +/- 19%, nicorandil
      group 49.3 +/- 24%, P = 0.012) whereas nitroglycerin exhibited a borderline
      effect (62.5 +/- 15%, P = 0.054). Both treatments resulted in improved regional
      systolic shortening of the reperfused segment at the end of the experiments but
      this was not significant. At these drug dosages the direct cardioprotective
      action of nicorandil is slightly superior to nitroglycerin. This may be ascribed
      to its K-channel opening property associated with reduced regional myocardial
      oxygen consumption before the onset of ischaemia.

PMID- 7588892
TI  - Plasma leukocyte elastase concentration in angiographically diagnosed coronary
      artery disease.
AB  - OBJECTIVE: To evaluate the clinical usefulness of leukocyte elastase
      determination in the diagnosis of coronary artery disease (CAD). BACKGROUND:
      Recent research has shown the important role of elastase, a proteolytic enzyme
      released by neutrophils, in the pathogenesis of CAD. METHODS: 141 patients
      underwent coronary angiography during investigation of chest pain and/or heart
      valve disease. Ninety-six had coronary lesions and 45 non-stenotic coronaries.
      The patients were characterized as regards presence or absence of angina (stable
      or unstable), family history of CAD, smoking, diabetes mellitus, hypertension,
      leukocyte counts, and plasma lipid and elastase concentrations. Among CAD-group
      patients, those with simple atheromatous plaques were distinguished from those
      with complex plaques. RESULTS: Elastase concentrations were greater in the CAD
      group than in the non-CAD group (49.7 +/- 2.8 micrograms.l-1; as against 29.5 +/-
      2.2 micrograms.l-1; P < 0.001), and greater among complex-plaque CAD patients
      than among simple-plaque CAD patients (65.2 +/- 5.3 micrograms.l-1 as against
      38.6 +/- 1.9 micrograms.l-1; P < 0.001). Logistic regression analysis showed (a)
      that the risk of CAD varied with elastase concentration, angina status, age and
      sex, increasing by 11% for every 1 microgram.l-1 increase in elastase
      concentration; and (b) that among CAD patients the risk of complex plaques was
      greatest for those with unstable angina and high elastase concentration,
      increasing by 6% for every 1 microgram.l-1 increase in elastase concentration.
      CONCLUSIONS: Peripheral blood leukocyte elastase concentration is a sensitive
      diagnostic marker of CAD. High values suggest the presence of complex
      atheromatous plaques.

PMID- 7588893
TI  - Relationship between ventilatory threshold and onset of ischaemia in ECG during
      stress testing.
AB  - The study was carried out to determine the relationship between ventilatory
      threshold and the onset of ischaemia, as shown on the ECG (horizontal and/or
      descending ST depression of 0.05 mV, on average). Twenty-seven male patients
      (aged 58 +/- 7 years) with angiographically documented coronary artery disease
      (CAD) were assessed by cardiopulmonary exercise testing without medication.
      Oxygen uptake (VO2), heart rate (HR), rate-pressure-product (RPP) and blood
      lactate were measured and/or calculated every 30 s during exercise. In addition,
      10 patients, comparable with the above group, were examined to find out the acute
      effects of isosorbide dinitrate (ISDN) at ventilatory threshold in relation to
      ischaemic threshold. The first cardiopulmonary exercise test was carried out
      without medication, the second 1 h later with 5 mg ISDN, taken sublingually 30
      min before the test. RESULTS: (means, SD): (1) The mean ventilatory threshold
      preceded the ischaemic threshold in relation to exercise capacity (48 +/- 14 vs
      55 +/- 20 watts; P < 0.05), VO2.kg-1 (10.0 +/- 2.2 vs 12.0 +/- 2.9 ml.kg-1.min; P
      < 0.05), HR (93 +/- 15 vs 100 +/- 16.min-1; P < 0.01), RPP (15095 +/- 4424 vs
      17166 +/- 5245; P < 0.01) and blood lactate (1.28 +/- 0.53 vs 1.44 +/- 0.60
      mmol.l-1; P < 0.05). (2) This relationship was observed more often in the
      subgroup of patients with angina during cardiopulmonary exercise testing or with
      myocardial infarction or with three-vessel disease than in patients without
      angina or infarction or with one- and two-vessel disease.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7588894
TI  - Percutaneous transluminal coronary angioplasty of aorta ostial, non-aorta ostial,
      and branch ostial stenoses: acute and long-term outcome.
AB  - The acute and long-term outcome of 198 patients who underwent coronary
      angioplasty of ostial stenoses was evaluated. Procedural success was achieved in
      85% of aorta ostial stenoses, 90% of non-aorta ostial stenoses, and 87% of branch
      ostial stenoses (P = 0.84). A major complication occurred in 5.9%, 6.3%, and 6.9%
      of patients who underwent aorta ostial, non-aorta ostial, and branch ostial
      stenosis angioplasty, respectively (P = 0.97). A greater residual stenosis (P =
      0.005) resulted from angioplasty of aorta ostial lesions despite a greater
      inflation frequency (P < 0.001), inflation pressure (P < 0.001), and total
      inflation duration (P < 0.001). The restenosis rate was higher for aorta ostial
      lesions (71%) when compared to non-aorta ostial (60%) and branch ostial lesions
      (32%) (P = 0.01). However, since the denominator included only the 49% who
      returned for repeat coronary angiography, the exact angiographic restenosis rate
      cannot be determined. The cumulative probability of survival was 99% at 1 year
      and 93% at 3 years. The 1 and 3 year freedom from death, myocardial infarction,
      bypass surgery, and repeat angioplasty was 70% and 57%, respectively. At census,
      57% were asymptomatic, and only 9% suffered severe angina. Coronary angioplasty
      of ostial stenoses can be carried out with an acceptable success and complication
      rate, and provides good symptomatic relief and favourable long-term outcome.
      Randomized trials to compare new angioplasty technology with balloon angioplasty
      will be necessary to select the best device therapy for ostial lesions.

PMID- 7588895
TI  - Efficacy and safety of collagen implants for haemostasis of the vascular access
      site after coronary balloon angioplasty and coronary stent implantation. A
      randomized study.
AB  - A vascular haemostasis device has recently been introduced that allows
      percutaneous implantation of collagen plugs for haemostatic sealing of puncture
      sites even under full anticoagulation. This study assessed the incidence of
      access site complications after collagen plug implantation in patients with
      percutaneous coronary angioplasty (PTCA) or coronary stenting. Seventy-eight
      patients with coronary stenting and 231 patients with PTCA were included in a
      prospective randomized trial comparing collagen plug implantation to conventional
      haemostasis. Collagen plug implantation significantly reduced median manual
      compression times from 45 min (quartiles: 35 min, 51 min) to 5 min (4 min, 6 min)
      after stenting (P = 0.001) and from 27 min (20 min, 32 min) to 5 min (4 min, 6
      min) after PTCA (P = 0.0001). After stenting, in 15 of the 37 patients with
      collagen implants, access site complications occurred (11 pseudoaneurysms, one
      arteriovenous fistula, three bleedings requiring blood transfusion, four local
      infections). The complication rate in the control group (17/41) was not
      significantly different (P = 0.88). After PTCA, three of the 114 control group
      patients suffered access site complications, while in the corresponding treatment
      group of 117 patients, complications occurred in 16 (seven pseudoaneurysms, one
      arteriovenous fistula, six infections, two femoral occlusions, one bleeding with
      nerve compression; P = 0.0049). In conclusion, the vascular haemostasis device
      allows rapid sealing of the vascular access site even under full anticoagulation.
      Its use after PTCA was however associated with increased access site
      complications, particularly infections, and even after coronary stenting, failed
      to reduce the incidence of access site complications.

PMID- 7588896
TI  - Induction of transient third degree atrioventricular block during radiofrequency
      catheter ablation in a patient with ventricular tachycardia and remote myocardial
      infarction.
AB  - INTRODUCTION: Radiofrequency catheter ablation has been demonstrated to be an
      effective and safe therapy in patients with so-called idiopathic ventricular
      tachycardia, whereas the benefit/risk profile for ablation of ventricular
      tachycardia in patients with chronic myocardial infarction and severely
      compromised left ventricular function still needs to be determined. The present
      report describes the unintended induction of transient third-degree
      atrioventricular block in a patient with remote myocardial infarction who
      underwent radiofrequency catheter ablation of ventricular tachycardia. METHODS
      AND RESULTS: Endocardial catheter mapping and radiofrequency ablation were
      performed in a 57-year-old patient with chronic recurrent ventricular
      tachycardia, who had previously suffered from anterior and posterior wall
      myocardial infarction. Additionally, the patient presented with complete right
      bundle branch block during sinus rhythm. Radiofrequency energy applied to a
      critical site of the reentrant tachycardia at the left ventricular basal septum
      during sinus rhythm induced third-degree atrioventricular block after 20 s of
      current delivery, which lasted for 24 h. At this site, a presumable left bundle
      branch potential was recorded during sinus rhythm. CONCLUSIONS: Radiofrequency
      current application for ablation of ventricular tachycardia may induce third
      degree atrioventricular block in patients with remote myocardial infarction. When
      current is delivered to target sites at the left ventricular basal septum,
      radiofrequency energy should be applied during sinus rhythm to allow continuous
      monitoring of atrioventricular conduction. Special caution should be given to
      patients with right bundle branch block during sinus rhythm.

PMID- 7588897
TI  - Comparison and combination of late potentials and spectral turbulence analysis to
      predict arrhythmic events after myocardial infarction in the Post-Infarction Late
      Potential (PILP) Study.
AB  - Ventricular late potentials detected at the end of the QRS complex by the signal
      averaged ECG have been shown to predict arrhythmic events after acute myocardial
      infarction. Spectral turbulence analysis is a novel technique for detecting
      abnormalities of cardiac electric activation inside the QRS complex. The purpose
      of this study was to combine these two analysis methods in order to increase the
      predictive power of the signal-averaged ECG in post-infarction patients. The
      study comprised a prospective series of 778 males under 66 years of age who
      survived the acute phase of myocardial infarction. Signal-averaged ECG recordings
      were performed before hospital discharge 2 to 3 weeks after infarction. The
      original Simson method was used for recording and analysing the time-domain
      signal-averaged ECG. Spectral turbulence analysis was performed using the same
      averaged vector magnitude QRS complexes (Del Mar Avionics). During the follow-up
      period of 6 months, 33 patients (4.2%) had an arrhythmic event (sustained
      monomorphic ventricular tachycardia in 13 cases, ventricular fibrillation in
      eight cases and sudden cardiac death in 12 cases). The predictive power of late
      potentials in the time domain, spectral turbulence analysis and their
      combinations were tested together with clinical variables using the Cox
      regression method.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588886
TI  - Torsade de pointes--the Achilles' heel of arrhythmia therapy with drugs that
      prolong the cardiac action potential.

PMID- 7588898
TI  - Influence of coronary artery bypass grafting on ventricular late potentials as a
      predictive factor for ventricular arrhythmias during short- and long-term follow
      up.
AB  - Ventricular late potentials have been identified as a prognostic factor in the
      prediction of ventricular arrhythmias in patients after myocardial infarction. In
      this prospective study the possible impact of late potentials on the prediction
      of ventricular arrhythmias in the short- and long-term follow-up after coronary
      artery bypass grafting was evaluated. In 188 patients (165 men, 23 women, age 57
      +/- 8 years) with chronic coronary heart disease 48 (26%) had late potentials
      before bypass grafting; after the procedure this was reduced to 39 (21%) (ns). In
      16 (33%) of the 48 patients with late potentials before bypass grafting, late
      potentials were no longer present in the short-term follow-up (9 +/- 6 days).
      Conversely, seven (5%) of the 140 patients without late potentials before bypass
      grafting had late potentials in the short-term follow-up after grafting. Nine
      (19%) of the 48 patients with late potentials before bypass grafting had
      ventricular arrhythmias in the peri-operative phase, which had to be treated with
      antiarrhythmic agents. In contrast, only three (2%) of the 140 patients without
      late potentials before bypass grafting had to be treated for ventricular
      arrhythmias (P < 0.001). In the long-term follow-up of 29 +/- 3 months, there
      were no events in the group of 149 patients without late potentials after
      grafting. In the 39 patients with late potentials after grafting, there were two
      (5%) events (two patients with arrhythmic syncope). CONCLUSIONS: (1) Patients
      with late potentials before bypass grafting have a markedly higher risk of
      developing serious ventricular arrhythmias in the peri-operative period than
      patients without late potentials. (2) Patients without late potentials have a
      very low risk of developing serious ventricular arrhythmias in the peri-operative
      period. (3) During long-term follow-up there was only a low probability of
      developing symptomatic ventricular arrhythmias in patients with or without late
      potentials.

PMID- 7588899
TI  - Physiological and pathological responses of TU waves to class Ia antiarrhythmic
      drugs.
AB  - Abnormal repolarization associated with torsades de pointes is expressed as QT
      prolongation. The physiological response to class Ia antiarrhythmic drugs is also
      reflected in prolongation of the QT interval. However, the essential difference
      between pathological and physiological prolongation is not clear. The purpose of
      this investigation was to differentiate between pathological and physiological
      changes in the repolarization waves of surface electrocardiograms (ECG) induced
      by class Ia drugs. In 18 patients without a history of torsades de pointes or
      syncope (control group), TU waves were compared before and after the
      administration of class Ia drugs (physiological response). In eight patients with
      torsades de pointes induced by class Ia drugs (torsades de pointes group), the TU
      waves at torsades de pointes were compared with those before drug administration
      (pathological response). In the control group, although the QTc (measured in lead
      II and corrected for heart rate by Bazett's formula) was increased significantly
      (0.40 +/- 0.04 to 0.44 +/- 0.05 s, P < 0.001), the U-amp (amplitude of the U wave
      measured in a precordial lead where the T and U waves were clearly
      differentiated) remained unchanged. In the torsades de pointes group, however,
      the QTc was increased (0.42 +/- 0.04 to 0.54 +/- 0.07 s, P < 0.02); the U-amp was
      also increased, significantly (0.09 +/- 0.07 to 0.27 +/- 0.18 mV, P < 0.05).
      Thus, enlargement of the U wave may help to differentiate between the
      physiological and pathological responses to class Ia drugs.

PMID- 7588900
TI  - Autonomic, ischaemic, circadian and rhythmic factors as causes of the spontaneous
      variability of ventricular arrhythmias.
AB  - Ventricular arrhythmias present with strongly varying intensity. This spontaneous
      variability makes it difficult to use one of the existing arrhythmia grading
      systems for risk or therapy efficacy studies. We attempted to explain the
      variability by the changing autonomic, ischaemic, circadian, and rhythmic
      factors. Four (two learning, two test) 24-h Holter tapes were made within one
      month in 31 patients with chronic frequent ventricular ectopic beats of
      miscellaneous aetiology and under constant drug regimen. The data were segmented
      into 5-min episodes, in which ectopy (dependent variable) was measured, together
      with heart rate, amount of heart rate variability, fraction low-frequency heart
      rate variability, ST depression, and clock time (independent variables). Forty
      three percent of the fluctuations in arrhythmia incidence could be explained with
      a multiple regression procedure, and more than 50% of the variance in arrhythmia
      incidence could be explained in 36% of the cases. Our study demonstrates that
      much of the spontaneous variability of ventricular arrhythmias can be attributed
      to the varying conditions. This method of dealing with arrhythmia variability
      might lead to an alternative to the current arrhythmia grading systems used in
      risk and drug efficacy studies.

PMID- 7588901
TI  - Double-chambered right ventricle.
AB  - Between May 1974 and December 1993, 37 patients (0.75%) with a double-chambered
      right ventricle underwent surgical repair. The patients ranged in age from 11
      months to 12 years (mean 4 +/- 1.1 years). Cardiac catheterization was performed
      in 36 patients. The proximal right chamber pressure was 118 +/- 10 mmHg and the
      mean ventricular gradient pressure was 75 +/- 10 mmHg. A ventricular septal
      defect was present in 36 cases and fixed subaortic stenosis in eight.
      Longitudinal right ventriculotomy, group I, was performed in 19 patients (51.3%):
      11 had a perimembranous ventricular septal defect and eight an infundibular
      ventricular septal defect. Combined pulmonary arteriotomy and right atriotomy,
      group II, was performed in 18 patients (48.7%): 17 patients had a perimembranous
      ventricular septal defect. The ventricular septal defect was closed using a
      double velour patch in 26 patients, continuous suture in four and a Gore-Tex
      patch in six. In the ventriculotomy group one patient died shortly after the
      operation (following pulmonary complication), and ten patients required inotropic
      support. Two patients developed patch dehiscence and underwent reoperation. There
      were no complications in group II patients who underwent right atriotomy.
      Associated cardiac anomalies were corrected in all patients. Follow-up of 6.5 +/-
      3.1 years after operation showed that 36 patients were alive and asymptomatic.
      CONCLUSION: the transatrial approach with pulmonary arteriotomy is an appropriate
      and effective double-chambered right ventricle correction even if it is
      associated with a perimembranous ventricular septal defect.

PMID- 7588902
TI  - Treatment with various antibiotics of experimental endocarditis caused by
      penicillin-resistant Streptococcus sanguis.
AB  - BACKGROUND: Streptococcus sanguis currently accounts for one-half of viridans
      streptococci. Treatment has become complicated due to the increase in resistance
      to penicillin and cephalosporins. The aim of the study was to assess the efficacy
      of various antibiotics as monotherapy and in association with gentamicin, in a
      experimental model of infective endocarditis in rabbits. The effects were
      compared with a control group and a group given classical penicillin-gentamicin
      treatment. MATERIAL AND METHODS: Infective endocarditis was induced in 180
      rabbits with a clinical isolate of Streptococcus sanguis. Treatment was started
      48 h after infection, and lasted 5 days. The animals were divided into nine
      groups of 20 rabbits: G1, untreated controls; G2, penicillin-gentamicin; G3,
      clindamycin-gentamicin; G4, imipenem; G5, imipenem-gentamicin; G6, teicoplanin;
      G7, teicoplanin-gentamicin; G8, vancomycin and G9, vancomycin-gentamicin.
      Response to therapy was evaluated by mortality curves, as negative blood
      cultures, concentration of S. sanguis in aortic vegetations and rate of
      sterilization of vegetations. RESULTS: Vegetation weight was significantly lower
      in treated groups than in controls; lower weights were found in G5, 6, and 9. G9
      sterilized 75% of the vegetations. Death occurred in 25% of the control group and
      in 4.76% of G6 and 7. Blood cultures became negative most rapidly in G9.
      CONCLUSIONS: Combined treatment with vancomycin-gentamicin may be highly
      efficacious in patients with endocarditis caused by penicillin-resistant
      Streptococcus sanguis. Other combinations, such as imipenem-gentamicin and
      teicoplanin-gentamicin, may be also advantageous.

PMID- 7588903
TI  - 'White-coat' hypertension in patients with newly diagnosed hypertension:
      evaluation of prevalence by ambulatory monitoring and impact on cost of health
      care.
AB  - To evaluate the prevalence of 'white-coat' hypertension in patients with newly
      diagnosed hypertension, 255 subjects (131 males and 124 females) underwent 24-h
      ambulatory blood pressure monitoring. Patients with 24-h systolic and diastolic
      blood pressure < 135/85 mmHg were classified as white-coat hypertensives and the
      remaining as sustained hypertensives. On the assumption that white-coat
      hypertensives may not need to take antihypertensive medication, we evaluated the
      impact on cost of health care of two strategies based essentially on treating all
      patients according to casual blood pressure, or ambulatory blood pressure
      monitoring, followed by drug treatment in sustained hypertensives only. Of the
      255 hypertensives studied, 54 (21%), confidence interval 16%, 26%, were
      classified as white-coat hypertensives. The age, sex-ratio and body mass index
      did not differ between the white-coat and the sustained hypertensive subjects.
      The strategy of monitoring all patients and of treating only the sustained
      hypertensives resulted in a substantial coat saving, which was calculated to be
      about 110,000 U.S.A. dollars over a period of 6 years. In conclusion, white-coat
      hypertensives are frequent among patients with newly diagnosed hypertension, and
      they do not differ from sustained hypertensives as regards demographic data.
      Ambulatory blood pressure monitoring, when used to decide whether or not to treat
      pharmacologically, increases the cost-effectiveness of treatment for hypertension
      and reduces the cost of health care.

PMID- 7588904
TI  - Assumed oxygen consumption based on calculation from dye dilution cardiac output:
      an improved formula.
AB  - This study was performed because of observed differences between dye dilution
      cardiac output and the Fick cardiac output, calculated from estimated oxygen
      consumption according to LaFarge and Miettinen, and to find a better formula for
      assumed oxygen consumption. In 250 patients who underwent left and right heart
      catheterization, the oxygen consumption VO2 (ml.min-1) was calculated using
      Fick's principle. Either pulmonary or systemic flow, as measured by dye dilution,
      was used in combination with the concordant arteriovenous oxygen concentration
      difference. In 130 patients, who matched the age of the LaFarge and Miettinen
      population, the obtained values of oxygen consumption VO2(dd) were compared with
      the estimated oxygen consumption values VO2(lfm), found using the LaFarge and
      Miettinen formulae. The VO2(lfm) was significantly lower than VO2(dd); -21.8 +/-
      29.3 ml.min-1 (mean +/- SD), P < 0.001, 95% confidence interval (95% CI) -26.9 to
      -16.7, limits of agreement (LA) -80.4 to 36.9. A new regression formula for the
      assumed oxygen consumption VO2(ass) was derived in 250 patients by stepwise
      multiple regression analysis. The VO2(dd) was used as a dependent variable, and
      body surface area BSA (m2). Sex (0 for female, 1 for male), Age (years), Heart
      rate (min-1) and the presence of a left to right shunt as independent variables.
      The best fitting formula is expressed as: VO2(ass) = (157.3 x BSA + 10.0 x Sex -
      10.5 x In Age + 4.8) ml.min-1, where ln Age = the natural logarithm of the age.
      This formula was validated prospectively in 60 patients. A non-significant
      difference between VO2(ass) and VO2(dd) was found; mean 2.0 +/- 23.4 ml.min-1, P
      = 0.771, 95% Cl = -4.0 to +8.0, LA -44.7 to +48.7. In conclusion, assumed oxygen
      consumption values, using our new formula, are in better agreement with the
      actual values than those found according to LaFarge and Miettinen's formulae.

PMID- 7588905
TI  - Transvenous defibrillator implantation in patients with persistent left superior
      vena cava and right superior vena cava atresia.
AB  - In this report a transvenous cardioverter defibrillator implantation is described
      in two patients with a persistent left-sided superior vena cava and right SVC
      atresia. In the first case, manoeuvring of the guide wire inserted through the
      left subclavian vein into the SVC proved impossible, revealing a left SVC
      originating from the left brachiocephalic vein with an acute corner. Changing the
      side of implantation and inserting a CPI Endotak catheter through the right
      subclavian vein, the lead was easily advanced through the left SVC into the
      coronary sinus and then into the right atrium with the tip abutting the lateral
      atrial wall. Subsequent manoeuvres allowed passage of the tip of the catheter
      into the right ventricular apex with the proximal defibrillation coil of the
      Endotak lead in the low left SVC, with its distal limit at the junction with the
      coronary sinus. A biphasic waveform single pathway RV - > left SVC successfully
      defibrillated with a stored energy of 5 J. In the second patient, implantation of
      a transvenous Medtronic system was possible from a left infraclavicular approach.
      A tripolar RV coil was inserted into the right ventricle via the persistent left
      SVC and contiguous coronary sinus. Because of the acute angle required to enter
      the RV in this second case, the RV lead was looped in the right atrium in order
      to enter the RV in a satisfactory, albeit atypical RV location. This patient was
      successfully defibrillated with a 5 J monophasic waveform delivered between the
      RV coil, a CS/left SVC coil, and a subcutaneous patch. In conclusion, both of
      these patients illustrate the ability to use transvenous ICDs successfully in
      patients with persistent left superior vena cava although the implantation
      technique deviates substantially from traditional methods.

PMID- 7588906
TI  - Identification of right atrial thrombi using transoesophageal echocardiography.
AB  - The in vivo diagnosis of right atrial thrombus is difficult by transthoracic
      echocardiography and it is likely that small thrombi are underdiagnosed using
      this approach. Transoesophageal echocardiography provides an unobstructed view of
      cardiac structures and the great vessels. In this report we describe the findings
      in five patients with right atrial thrombi that illustrate the potential
      usefulness of transoesophageal echocardiography for both the initial diagnosis
      and the subsequent management of these patients.

PMID- 7588907
TI  - Percutaneous balloon valvuloplasty for concurrent mitral, aortic and tricuspid
      rheumatic stenosis.
AB  - Percutaneous balloon valvuloplasty has been used with good results to treat
      rheumatic mitral stenosis. However, its use in degenerative aortic stenosis has
      shown many limitations. There is little information about balloon valvuloplasty
      in tricuspid and aortic rheumatic stenosis. This article describes two patients
      with combined rheumatic mitral, aortic and tricuspid stenosis in which triple
      percutaneous valvuloplasty was performed in a single procedure.

PMID- 7588908
TI  - Ventricular aneurysm and myocarditis in a child with the hyperimmunoglobulin E
      syndrome.
AB  - A 2-year-old Omani child with hyperimmunoglobulin E syndrome (HIES) had a 5-week
      illness characterized by fever, heart failure and acute mitral regurgitation.
      Echocardiographic studies showed the evolution of an apical left ventricular
      aneurysm during this illness.

PMID- 7588910
TI  - Studies on conversion of recent onset AF to sinus rhythm have to be controlled.

PMID- 7588909
TI  - Superior vena cava syndrome after implantation of a transvenous cardioverter
      defibrillator.
AB  - Superior vena cava syndrome is a rare, but nevertheless well known complication
      of permanent pacemaker implantation. Nowadays cardioverter defibrillators are
      also routinely implanted transvenously. A superior vena cava syndrome occurred in
      a 48-year-old female 2 years after implantation of cardioverter defibrillator.
      The clinical problem, in the presence of a predisposing thrombophilic condition
      (circulating lupus anticoagulant), resolved only partially after treatment with
      thrombolytics and oral anticoagulation. This syndrome should be recognized as a
      possible important complication of defibrillator therapy and requires lifelong
      anticoagulation.

PMID- 7588911
TI  - Heart disease and mortality in a Mediterranean population.

PMID- 7588912
TI  - Community programmes for cardiovascular disease prevention in changing societies.

PMID- 7588914
TI  - Identification of patients at risk of major cardiac events after vascular
      surgery. A role for stress echocardiography?

PMID- 7588913
TI  - What is the role of anti-ischaemic treatment in patients with ventricular
      tachyarrhythmias after a previous myocardial infarction?

PMID- 7588915
TI  - Coronary artery disease: prevention of progression and prevention of events.

PMID- 7588916
TI  - Myocardial reperfusion injury: experimental evidence and clinical relevance.
AB  - Critically timed reperfusion is a prerequisite for survival of ischaemic
      myocardium. However, reperfusion may have an injurious component, which in
      experimental models appears to be mediated by reperfusion-induced augmentation of
      the inflammatory response and generation of reactive oxygen free radicals. Four
      expressions of myocardial reperfusion injury have been defined, i.e. reperfusion
      arrhythmias, post-ischaemic contractile dysfunction (myocardial stunning),
      coronary vascular and microvascular reperfusion injury, and acceleration of
      necrosis in irreversibly injured cells/precipitation of necrosis in reversibly
      injured cells. Mechanical and pharmacological reperfusion therapy is well
      established in clinical cardiology, and this article reviews the experimental
      data underlying the current view of myocardial reperfusion injury, and considers
      the clinical relevance of this phenomenon.

PMID- 7588917
TI  - Guidelines for the diagnosis of heart failure. The Task Force on Heart Failure of
      the European Society of Cardiology.

PMID- 7588918
TI  - Cardiovascular risk factor changes in the Kilkenny Health Project. A community
      health promotion programme.
AB  - The Kilkenny Health Project was a community research and demonstration programme
      which aimed to reduce risk of cardiovascular disease in a county in the south
      east of Ireland with a total population of approximately 70,000. The health
      promotion programme was carried out in Kilkenny from 1985 to 1992. Outcome
      evaluation was by means of population surveys of independent samples of men and
      women aged 35 to 64 years in Kilkenny (n approximately 800) and in the reference
      county (n approximately 600) in 1985/1986 and in 1990/1991. Survey methods for
      health behaviour questionnaires and risk factor measurements were similar to
      those of the WHO MONICA Project. Mean systolic blood pressure (SBP) declined
      significantly (P < 0.01) in men and women in both counties, from 144.0 by 5.4
      mmHg and from 143.2 by 5.4 mmHg in men and from 139.5 by 7.7 mmHg and from 136.5
      by 6.6 mmHg in women in the intervention and reference counties. The prevalence
      of hypertension declined from 23.1% by 2.8% and from 26.1% by 6.0% in men in the
      two counties. Prevalence declined from 24.1% by 6.2% (P < 0.05) in women in the
      intervention county but was unchanged, increasing by 0.5% from 17.5%, in women in
      the reference county. Mean serum total cholesterol declined from 6.04 mmol.l-1 by
      0.09 mmol.l-1 and from 6.00 by 0.44 mmol.l-1 (P < 0.01) in men and from 6.01 by
      0.36 (P < 0.01) and from 5.90 by 0.31 (P < 0.01) in women in the intervention and
      reference counties, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588919
TI  - Prevalence of coronary heart disease risk factors in northern-Italian male and
      female employees.
AB  - A cross-sectional study of 2650 male and 751 female employees of the IBM company
      in the Milan area was conducted in 1987 to compare risk profiles for coronary
      heart disease between men and women and to analyse the awareness of risk status
      of people at risk. After age adjustment, the rate of cigarette smoking was higher
      in women (35%) than in men (25%). Other coronary heart disease risk factors were
      more common in men than in women. After controlling for age, 38% of the men and
      19% of the women met the study criteria for hypertension, and 22% of the men and
      17% of the women had high blood cholesterol. However, an analysis by age groups
      showed that, although in the younger age groups women had lower levels of
      cardiovascular risk factors, except smoking, compared to men, in the age brackets
      50 or older women had similar or more adverse risk factor profiles than men. Of
      the people with hypertension, only 22% of the men and 19% of the women were aware
      of their hypertension, and only 2% of the men and 4% of the women had successful
      control by drugs. Even when subjects with mild hypertension were excluded, high
      proportions of undiagnosed and uncontrolled hypertension were found in both
      sexes. Of the individuals with serum cholesterol > or = 240 mg.dl-1, less than
      half of the men and less than 20% of the women were aware of their high blood
      cholesterol levels. Multiple risk factors were frequently present in the same
      individuals, especially among males and older women.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7588921
TI  - Improvement in survival after myocardial infarction between 1978-85 and 1986-88
      in the REGICOR study. (Registre GIroni del COR) registry.
AB  - Aspirin, intravenous nitrates and fibrinolysis were being used by 1986 in Girona,
      Spain. These combined factors should be reflected in myocardial infarction
      patients' outcome. We assessed changes in 28-day and 3-year survival after a
      first myocardial infarction between 1978-85 and 1986-88 in the REGICOR (Registre
      GIroni del COR) registry. This included 1216 consecutive patients with a first
      transmural myocardial infarction (834 in 1978-85 and 372 in 1986-88). Their 28
      day and 3-year mortality rates were 14.6% and 8.8% respectively. Although
      patients admitted in the second period were more frequently hypertensive and
      diabetic, a history of angina was less common in patients admitted between 1978
      and 1985. After adjusting for diabetes, hypertension, age, and sex, the relative
      risk of 28-day mortality of those admitted in the second period was 0.65 (95%
      confidence interval 0.42-0.99). The lower severity, as measured by Killip class
      of patients in the second period, was the main (confounding) variable responsible
      for this protective effect. Three-year mortality of those surviving 28 days in
      1978-85 (8.3%) did not differ from 1986-88 (8.3%). In the second study period
      hospitalized patients with myocardial infarction in Girona, Spain showed a better
      28-day survival. It is possible that therapeutic and diagnostic refinements,
      together with other factors not controlled in the present study, have resulted in
      such an improvement. However, 3-year mortality remained unmodified among those
      surviving 28 days.

PMID- 7588920
TI  - Neurohormonal changes after acute myocardial infarction. Relationships with
      haemodynamic indices and effects of ACE inhibition.
AB  - To determine the neurohormonal response to angiotensin-converting enzyme (ACE)
      inhibition after acute myocardial infarction, 36 patients presenting within 6 h
      of the onset of chest pain were studied in a single regional cardiology service.
      In this double-blind study, 13 patients were randomized to receive captopril, 12
      patients received enalapril, and 11 patients received placebo, for 12 months. In
      patients receiving placebo, acute myocardial infarction was associated with
      activation of the renin-angiotensin-aldosterone and sympathetic nervous systems,
      and stimulation of plasma brain natriuretic peptide and atrial natriuretic
      peptide levels. ACE inhibition did not significantly alter circulating levels of
      norepinephrine, brain natriuretic peptide or atrial natriuretic peptide. Compared
      with placebo, enalapril induced a steep decline in plasma ACE activity, and
      plasma angiotensin II levels were reduced by both ACE inhibitors. Using grouped
      data, circulating levels of brain natriuretic peptide at the zero sampling time
      were significantly higher than atrial natriuretic peptide values. Brain
      natriuretic peptide levels at 72 h were significantly correlated with the
      radionuclide left ventricular ejection fraction measured 5 days and 3 months
      after infarction. Similar associations were observed for atrial natriuretic
      peptide and norepinephrine. We confirm activation of the renin-angiotensin
      aldosterone and sympathetic nervous systems after acute myocardial infarction.
      The atrial natriuretic peptide and brain natriuretic peptide and sympathetic
      nervous system responses to acute myocardial infarction were not significantly
      modified by ACE inhibition. Brain natriuretic peptide and atrial natriuretic
      peptide levels were significantly correlated with the left ventricular ejection
      fraction measured 5 days and again 3 months after myocardial infarction, and may
      prove a useful prognostic index.

PMID- 7588922
TI  - Prolonged proliferative response of smooth muscle cells after experimental
      intravascular stenting.
AB  - The purpose of this experimental in vivo study was to determine the time course
      of smooth muscle cell proliferation early and late after intravascular stenting
      compared to conventional balloon angioplasty in normal vessels. A balloon
      expandable 2.0 mm tantalum Strecker stent was placed in the right carotid artery
      of 33 male New Zealand White rabbits after they had been fed a 0.5% cholesterol
      diet for 28 days. In addition, balloon angioplasty was performed in 27 of the
      animals; 19 contralateral vessels served as controls without treatment. The
      vessels were excised at 7, 14, 28, 42 or 90 days after treatment. During the
      final 18 h before the rabbits were killed, bromodeoxyuridine (BrdU) was applied
      and proliferating cells were detected by using a monoclonal antibody against
      BrdU. In histological cross sections the proportion of cells undergoing DNA
      synthesis was determined. Analysis was performed separately in the intimal and
      medial layers. Additionally, the area adjacent to the stent wire was compared
      with the intermediate area. Smooth muscle cells were identified by alpha-actin
      staining. Intimal wall thickness increased from 23 +/- 28 microns (control group
      without intervention) to 323 +/- 84 microns within 42 days after stenting (P <
      0.01), and to 81 +/- 82 microns at day 42 after balloon angioplasty (P < 0.05).
      However, between 42 and 90 days following stent implantation a significant (P <
      0.05) decrease in neointimal thickness was observed (90 days: 215 +/- 15
      microns).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588923
TI  - The reactivity of the contralateral artery at the time of balloon dilation during
      coronary angioplasty.
AB  - The response of the contralateral arteries was investigated during balloon
      angioplasty of the left anterior descending artery. Thirty patients were studied.
      Coronary arteriograms were obtained at baseline, during maximal balloon inflation
      and at the end of the procedure. Luminal diameter was measured by a quantitative
      coronary arteriography analysis system. During balloon inflation the luminal
      diameter of the proximal segment of the right coronary artery increased by 2.4 +/
      6% (P < 0.05), and that of the left circumflex artery increased by 0.6 +/- 6% (P
      = ns). Both returned to near baseline values after angioplasty. In patients with
      increased collaterals during balloon inflation the left circumflex proximal
      segment increased more significantly than in patients with unchanged collaterals.
      The luminal diameter of the distal segment of the right coronary artery increased
      by 9 +/- 8% (P < 0.001) and that of the left circumflex artery by 8 +/- 11% (P <
      0.01) during balloon inflation, returning to near baseline values after
      angioplasty. Thus, vasodilation of the contralateral arteries during balloon
      inflation at the time of coronary angioplasty occurs mainly in the distal
      segments, and appears to be related to an increase in collateral filling.

PMID- 7588925
TI  - Contractile state is the major determinant of functional outcome in patients with
      left ventricular dysfunction treated with enalapril.
AB  - Large-scale drug trials have focused primarily on mortality and morbidity and
      less on the functional state of the myocardium. A model was developed to assess
      myocardial contractile state in patients with left ventricular (LV) dysfunction
      and to address the questions of differences in function between patients with and
      without overt heart failure, effects of enalapril, and best predictors of
      functional outcome. Pressure-angiographic data were obtained from 16 patients
      with overt heart failure and 47 without heart failure. Repeat studies were
      conducted in 41 patients following 1 year's treatment with enalapril or placebo.
      Left ventricular silhouettes were divided into 18 segments to estimate regional
      ejection fraction, wall stress and myocardial damage (% myocardial damage).
      Contractile state was assessed and ranked by ejection rate-preload-afterload
      relationships and by a score method based on 10 myocardial and ventricular
      function parameters. End-diastolic and end-systolic volumes (EDV, ESV) were
      significantly greater (P < 0.001), ejection fraction (EF) lower (P < 0.009), %
      myocardial damage greater (P < 0.008) and contractile state more depressed in
      patients with overt heart failure. Changes in EDV and ESV (delta placebo vs delta
      enalapril) were significant (delta EDV, P < 0.003; delta ESV, P < 0.014).
      Directional shifts in the diastolic pressure-volume relationships with enalapril
      or placebo depended primarily on the basal contractile state and diastolic volume
      range. The best single predictors of post-treatment EF were the score index (a
      surrogate parameter for the contractile state) and ESV. Added benefits of
      enalapril include the prevention of further dilatation in patients with less
      depressed contractile state and delay in the onset of heart failure. Asymptomatic
      patients with LV dysfunction should also be considered for angiotensin converting
      enzyme (ACE) inhibitor therapy.

PMID- 7588924
TI  - Alterations of sympathovagal balance in patients with hypertrophic and dilated
      cardiomyopathies assessed by spectral analysis of RR interval variability.
AB  - Spectral analysis of RR interval variability was performed in 35 ambulatory
      patients with early hypertrophic cardiomyopathy (HCMa, NYHA class I), 21
      hospitalized patients with advanced hypertrophic cardiomyopathy (HCMh, NYHA class
      II or III), and 18 hospitalized patients with dilated cardiomyopathy (DCMh, NYHA
      class I, II or III). Twenty-nine ambulatory subjects (COTa) and 20 hospitalized
      volunteers (COTh) served as normal controls. The RR interval standard deviation
      (SD), the high-frequency power (HF: 0.15-0.40 Hz) corrected by the mean RR
      interval (CCVHF) and the normalized unit of the HF power (NUHF) served as markers
      of vagal modulation. Low-frequency power (LF: 0.04-0.15 Hz) corrected by the mean
      RR interval (CCVLF) and the normalized unit of LF power (NULF) were markers of
      sympathetic modulation. The LF/HF ratio was an index of sympathovagal balance.
      There was no significant difference in the SD, CCVHF, NUHF, CCVLF, NULF or the
      LF/HF ratio between the HCMa and COTa groups. At night, the SD was lower in the
      HCMh group relative to the COTh group (P < 0.01). The HCMh group demonstrated
      lower CCVHF and NUHF values (P < 0.01), higher NULF values (P < 0.01) and higher
      LF/HF ratios (P < 0.05) at night relative to the COTh group. Two patients who
      later died suddenly in the HCMh group had markedly reduced CCVHF values (0.2
      0.8%) relative to the survivors in the group (mean +/- SD in the morning,
      afternoon and night, 1.07 +/- 0.43%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588926
TI  - The clinical significance of coronary anatomy in post-infarct patients with late
      sustained ventricular tachycardia or ventricular fibrillation.
AB  - The role of ischaemia in post-infarct patients with ventricular tachyarrhythmias
      is not firmly established. Using coronary angiography, 82 post-infarct patients
      with sustained ventricular tachycardia or fibrillation were subclassified into
      three groups. Fourteen patients (17%) had significant coronary artery disease,
      suggesting that ischaemia was the primary cause (group A). In 13 patients (16%)
      ischaemia was considered a coexistent factor (group B). In 55 patients (67%)
      ischaemia did not play a role (group C). The 1-year cumulative arrhythmia-free
      rate was 100%, 75%, 68% and the 2-year arrhythmia-free rate 100%, 56%, 52% for
      groups A, B and C, respectively. Using life-table analysis, group A had the most
      favourable long-term outcome in relation to arrhythmia recurrence. Outcomes of
      groups B and C were comparable. In a univariate analysis, arrhythmia recurrence
      was determined by the arrhythmogenic role of ischaemia, the left ventricular
      ejection fraction and the time from the old infarct to the index arrhythmia. In
      the absence of arrhythmic events in group A, multivariate analysis of groups B
      and C identified depressed ejection fractions (RR 0.69, CI 0.49-0.98) and a
      prolonged time interval from the last infarct (> 5 years, RR 2.53, CI 1.12-5.75)
      as independent predictors for arrhythmia recurrence. The present approach helps
      in the identification of post-infarct patients with ventricular tachycardia and
      fibrillation, who benefit from stand-alone anti-ischaemic therapy. If ischaemia
      does not play a major arrhythmogenic role, prognosis depends on the left
      ventricular ejection fraction and on the age of the previous infarct.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7588927
TI  - Low vagal tone and supraventricular ectopic activity predict atrial fibrillation
      and flutter after coronary artery bypass grafting.
AB  - To investigate the impact of pre-operative autonomic balance and atrial ectopic
      activity on the risk of atrial fibrillation or flutter after aorto-coronary
      artery bypass surgery 24-h Holter monitoring was analysed in 102 patients before
      coronary artery bypass grafting. Index for vagal tone was calculated as %
      successive RR interval differences > 6%. Twenty-nine (28%) of the 102 patients
      developed atrial fibrillation or flutter. Independent predictors (90% confidence
      interval) of postoperative atrial fibrillation or flutter were identified by
      logistic regression analysis: the independent predictors were older age, relative
      risk 1.07.year-1 (1.02-1.12), vagal index < 10%, relative risk 4.50 (1.40-14.5),
      > or = 10 ectopic supraventricular beats . 24 h-1, relative risk 3.03 (1.05
      8.72), and one or more events of non-sustained supraventricular tachycardia,
      relative risk 3.02 (1.11-8.22). Thus, age of the patient, attenuated pre
      operative cardiac vagal modulation, ectopic supraventricular beats, and
      paroxysmal non-sustained supraventricular tachycardia are independent risk
      factors for the development of atrial fibrillation or flutter after coronary
      artery bypass surgery.

PMID- 7588928
TI  - Complex frequency-dependent interaction of class-I antiarrhythmic drugs as they
      affect intraventricular conduction.
AB  - We investigated the interaction of class-I antiarrhythmic drugs as they affect
      intraventricular conduction of human hearts in vivo. QRS duration in signal
      averaged electrocardiograms and standard electrocardiograms were measured as an
      index of intraventricular conduction time in 17 patients with implanted
      pacemakers at various pacing rates (100-180 ppm, VVI mode). Single intravenous
      administration of lidocaine, disopyramide or aprindine prolonged the QRS of
      signal-averaged electrocardiograms in a frequency-dependent manner. Lidocaine (n
      = 17) produced significant QRS prolongation from pre-drug control at rates > or =
      120 ppm (6.2 +/- 1.4% at 180 ppm), whereas disopyramide (n = 17) and aprindine (n
      = 17) did so from the lowest rate (8.9 +/- 1.8% to 12.3 +/- 2.9% at 100-180 ppm
      with disopyramide; 14.7 +/- 1.3% to 19.3 +/- 2.2% at 100-180 ppm with aprindine).
      Addition of lidocaine to disopyramide (n = 17) showed an additive effect; QRS
      prolongation was enhanced significantly by 1.4-2.8% at rates > or = 150 ppm. In
      contrast, addition of lidocaine to aprindine (n = 17) showed a subtractive
      effect; the QRS prolongation was attenuated significantly by 1.6-2.4% at rates <
      150 ppm. Combined intravenous administration of class-I antiarrhythmic drugs
      causes not only additive but also subtractive effects on the intraventricular
      conduction of the human heart, probably through their interaction on the sodium
      channel receptor.

PMID- 7588929
TI  - The value of dipyridamole echocardiography in risk stratification before vascular
      surgery. A multicenter study. The EPIC (Echo Persantine International Study)
      Group--Subproject: Risk Stratification Before Major Vascular Surgery.
AB  - PURPOSE: Patients undergoing major vascular surgery are at relatively high risk
      of cardiac events, and pharmacological stress echocardiography is increasingly
      used for peri-operative risk stratification. PATIENTS AND METHODS: One hundred
      and twenty-one patients undergoing vascular surgery (age 65 +/- 7 years) were
      studied by dipyridamole echocardiography testing in six different centres. Of the
      total 136 patients, 15 were subsequently excluded because surgery was either
      cancelled (n = 8) or postponed pending cardiac revascularization (n = 7) because
      of the presence of a 'high-risk' stress echo response (identified 'a priori' as a
      positive dipyridamole echocardiography testing with a dipyridamole-time < 5 min
      and/or a peak wall motion score index > 2, upon scoring each segment from 1 =
      normal to 4 = dyskinetic in an 11-segment model). RESULTS: No major complications
      occurred during dipyridamole echocardiography testing. Technically adequate
      images were obtained in all patients; however, in one patient only the low
      dipyridamole dose (56 mg.kg-1 over 4 min) was given to limit side effects. Of the
      121 patients undergoing surgery 28 (23%) had a positive test. Peri-operative
      events occurred in nine patients (8%): two deaths, two myocardial infarctions,
      five cases of unstable angina. Sensitivity and specificity of dipyridamole
      echocardiography testing for predicting cardiac events were 78% and 81%,
      respectively, with a positive predictive value of 25% and a negative predictive
      value of 98%. Dipyridamole echocardiography testing effectively singled out
      patients with, from those without, events, but neither clinical parameters, such
      as Detsky score, nor baseline echo parameters, such as resting wall motion score
      index or ejection fraction were able to distinguish between such patients.
      CONCLUSION: In conclusion, dipyridamole echocardiography testing is safe and well
      tolerated in patients undergoing major vascular surgery, and provides an
      effective pre-operative screening test for risk stratification of these patients
      mainly due to the extremely high negative predictive value. Stress
      echocardiography is a better discriminator than clinical and rest
      echocardiographic variables.

PMID- 7588931
TI  - Blunted humoral responses to mental stress and physical exercise in cardiac
      transplant recipients.
AB  - Since recent results have suggested that the relative neuroendocrine response to
      physical activity is exaggerated following cardiac transplantation, we studied
      the haemodynamic-neuroendocrine responses to mental stress, and to physical
      exercise, in heart transplant recipients free of antihypertensive medication. Ten
      patients were studied 1.7 years (mean) after transplantation and compared with 10
      age-matched controls. Plasma levels of catecholamines, renin activity,
      aldosterone, atrial natriuretic factor, calcitonin gene-related peptide (CGRP),
      and endothelin were measured, together with blood pressure and heart rate, during
      mental stress and graded, submaximal ergometry. Mental stress increased blood
      pressure in both groups (P < 0.02), but heart rate in controls only (P < 0.05).
      Noradrenaline did not change. Adrenaline rose in controls only (P < 0.05). Plasma
      renin activity increased in both groups (P < 0.02), while aldosterone increased
      in controls only P < 0.02). Atrial natriuretic factor, and endothelin were higher
      in patients (P < 0.01). Mental stress, however, did not induce any changes. No
      significant differences were found in relative changes (delta %), except for
      plasma renin activity which was greater in controls (P < 0.05). During ergometry,
      only delta % noradrenaline was greater in patients (P < 0.05). delta % for all
      other parameters were either of the same order as in controls, or blunted. Thus,
      apart from noradrenaline, cardiac transplant recipients, not receiving
      antihypertensive medication, do not show an exaggeration in the relative
      neuroendocrine response to mental or physical stress.

PMID- 7588930
TI  - 24-h ECG monitoring in patients with rheumatoid arthritis.
AB  - Although the main cardiac complication in patients with rheumatoid arthritis is
      subclinical pericarditis, mononuclear cell infiltrations into myocardium may
      cause cardiac arrhythmias and conduction defects. In order to examine these
      problems we evaluated 70 patients (53 women and 17 men) aged 18-83 years (average
      56.7 +/- 11.2) with classic or definite rheumatoid arthritis, according to
      diagnostic criteria. Duration of the disease was 1-35 years (average 8.7 +/-
      8.4). The control group comprised 70 patients admitted to hospital with
      degenerative joint disease, a duodenal ulcer, or who required treatment for
      ophthalmological or laryngeal reasons; these patients were matched for sex and
      age. In all patients standard 12-lead ECG investigations were performed, as well
      as 24-h ECG monitoring, using an Oxford Medical System device with two precordial
      leads CM5 and CS2, according to the Holter method. We analysed heart rate,
      conduction disturbances, and occurrence of arrhythmias, on the basis of generally
      assumed ECG criteria. Cardiac arrhythmias were found in 50% of patients with
      rheumatoid arthritis, and their occurrence was similar to that in the control
      group. Observed arrhythmias were independent of the progression of arthritis, the
      type of treatment administered, the familial occurrence of arthritis, the
      presence of manifestations pertaining to organs, the presence of rheumatoid
      factor, the stage of the disease according to Steinbrocker, or the presence of
      immune complexes in serum and HLA Dr antigens, which are regarded as fundamental
      in the pathogenesis of rheumatoid arthritis.

PMID- 7588934
TI  - Post-infarction left ventricle to right atrium fistula diagnosed by transthoracic
      Doppler echocardiography.
AB  - This is a report of a 63-year-old man who in the course of an inferior wall
      myocardial infarction developed a left ventricular aneurysm with communication to
      the right atrium and a haemodynamically significant intracardiac shunt. The
      unusual complication of a myocardial infarction was correctly diagnosed by
      transthoracic Doppler echocardiography, and later a successful surgical repair
      was done.

PMID- 7588932
TI  - Acute coronary occlusion secondary to radiofrequency catheter ablation of a left
      lateral accessory pathway.
AB  - A case of asymptomatic acute coronary occlusion secondary to radiofrequency
      catheter ablation of a left lateral accessory pathway is reported. Due to post
      procedural ST modifications of the surface ECG, a coronary angiography was
      performed which disclosed total occlusion of the first marginal branch of the
      left circumflex coronary artery. Acute myocardial infarction was confirmed by
      moderate cardiac enzyme release, abnormal myocardial perfusion scan and mild
      lateral hypokinesia at echocardiography. This rare but potentially harmful
      complication of interventional electrophysiology should be kept in mind and
      coronary angiography performed immediately when coronary occlusion related to
      radiofrequency application is suspected.

PMID- 7588933
TI  - Reversal of atropine-resistant atrioventricular block with intravenous
      aminophylline in the early phase of inferior wall acute myocardial infarction
      following treatment with streptokinase.
AB  - We report three patients with acute inferior myocardial infarction treated with
      aspirin (150 mg) and streptokinase (1.5 MU over 60 min), who developed atropine
      resistant bradyarrhythmias during or immediately following streptokinase. The
      bradyarrhythmias responded to aminophylline, thus avoiding the need for temporary
      pacing.

PMID- 7588935
TI  - Spontaneous coronary artery dissection in mitral stenosis.
AB  - Spontaneous coronary artery dissection is a rare disease that occurs most
      commonly in young people, especially in peripartum or postpartum women. It has
      rarely been diagnosed during life and has never before been observed associated
      with any other non-ischaemic heart disease. We report a case associated with
      mitral stenosis, in which successful valvular and coronary surgery were carried
      out. We speculate whether rheumatic coronary arteritis was a cause of the
      dissection.

PMID- 7588936
TI  - Thyroid scintigraphy and perchlorate discharge test in the diagnosis of
      congenital hypothyroidism.
AB  - Quantitative thyroid scanning using low doses of technetium-99m sodium
      pertechnetate was performed on 147 infants (55 males and 92 females) with
      congenital hypothyroidism detected through the national neonatal screening
      programme. Thirty-two (21.8%) were athyrotic, while 62 (42.2%) had an ectopic
      thyroid and 53 (36%) had a eutopic gland with increased 99mTc uptake (mean 17%;
      range, 5%-38%). The perchlorate discharge test (PDT) was performed in nine of the
      infants with ectopic glands and 15 with eutopic glands; the findings were
      consistent with an organification defect in 22 cases (seven ectopic and 15
      eutopic). Thyroid scintigraphy and PDT can add useful aetiological, genetic and
      prognostic information in the clinical evaluation of infants with congenital
      hypothyroidism detected by neonatal screening.

PMID- 7588937
TI  - Effects of non-linear flow and spatial orientation on technetium-99m
      hexamethylpropylene amine oxime single-photon emission tomography.
AB  - The effects of two post-acquisition corrections on the visual and quantitative
      analysis of technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon
      emission tomography (SPET) were determined. The corrections were for: (1) the
      improper spatial orientation of the patient data sets, and (2) the non-linear
      uptake of HMPAO across the blood-brain barrier. Reorienting the SPET image data
      sets removed observers' uncertainty in assessment caused by suspected head tilt;
      however, it increased their uncertainty due to perceived subtle perfusion
      deficits. Applying the correction to compensate for the decrease in uptake of
      HMPAO in high-flow regions resulted in an increase in the number of positive
      assessments. In a study involving 30 patient studies, intra-observer reliability
      increased from 62% to 83% (average of two observers) after applying both of the
      corrections, while inter-observer reliability improved from 62% to 81%.
      Quantitative methods of analysing the images are also affected by the
      corrections. In an ROI-based classification scheme, the quantitative assessments
      of more than one-half of the images are affected by the two corrections. These
      results need to be considered when comparing both quantitative and visual results
      from different studies in which the corrections may or may not have been applied.

PMID- 7588939
TI  - Myocardial technetium-99m sestamibi single-photon emission tomography as a
      prognostic tool in coronary artery disease: multivariate analysis in a long-term
      prospective study.
AB  - To date several studies have evaluated the accuracy of thallium-201 myocardial
      scan in risk stratification of coronary artery disease (CAD), while reports using
      technetium-99m methoxyisobutylisonitrile (MIBI), a tracer particularly suited to
      single-photon emission tomographic (SPET) imaging, are lacking. To rectify this
      omission, a prospective study was started in 1988 and at present 176 consecutive,
      and thus unselected, patients have been enrolled. All of them have been submitted
      to stress-rest MIBI SPET for the diagnosis or evaluation of CAD; 147 patients
      (121 males and 26 females, aged 53 +/- 9 years) have completed a surveillance
      period of at least 36 months following the scintigraphic study (range 36-60
      months, mean 43). Sixty-one patients had a documented previous myocardial
      infarction. The mean pre-test likelihood of CAD was 44% in the patients without
      prior infarction. The main anamnestic, clinical, EKG and scintigraphic findings
      were evaluated and statistically correlated with the incidence of ensuing cardiac
      events using both univariate (chi-square test) and multivariate analysis
      (logistic regression model). Twenty-nine patients suffered from a cardiac event
      during the follow-up period (i.e. three cardiac deaths, six myocardial
      infarctions and 20 cases of unstable angina). Statistical multivariate analysis
      identified MIBI scan as the only highly significant and independent prognostic
      predictor [P = 0.006, relative risk (RR) = 17.62]. In detail, the most important
      scintigraphic parameters were the presence of a reversible defect (P = 0.0089, RR
      = 5.11) and the extension of the stress perfusion defect (P = 0.0255, RR = 3.27).
      The presence of typical angina proved to be a slightly significant predictor (P =
      0.051, RR = 2.45), while no other examined parameter showed a significant
      correlation with a bad prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588938
TI  - Assessment of systolic wall thickening using technetium-99m
      methoxyisobutylisonitrile in patients with coronary artery disease: relation to
      thallium-201 scintigraphy with re-injection.
AB  - The results of resting planar ECG-gated technetium-99m methoxyisobutylisonitrile
      (99mTc-MIBI) imaging were compared with those of thallium-201 (Tl) re-injection
      after exercise-redistribution scintigraphy in 20 patients (19 men, 1 woman, mean
      age 53 +/- 10 years) with angiographically proven coronary artery disease. Eight
      normal subjects (seven men, one woman, mean age 50 +/- 8 years) constituted the
      control group. In these subjects, only resting 99mTc-MIBI imaging was performed.
      The standardized percent count increase from end-diastole to end-systole was
      calculated as an index of wall thickening in 13 segments for each study. Regional
      wall thickening index (WTI) and 99mTc-MIBI uptake were significantly different (P
      < 0.05) among segments classified as normal, reversible defects, irreversible
      defects with increased tracer uptake after re-injection (Re+) or irreversible
      defects with unchanged tracer uptake after re-injection (Re-) on Tl imaging.
      Furthermore, WTI and 99mTc-MIBI uptake were significantly higher (P < 0.05) in Re
      segments with moderate reduction of Tl uptake (> or = 50% of peak activity) than
      in Re- segments with severe reduction of Tl uptake (< 50% of peak activity). A
      significant relationship between WTI and the results of Tl scintigraphy was
      observed (rho = 0.71, P < 0.0001). The percentage of Re- segments with severe
      reduction of WTI was significantly higher compared to Re+ segments (64% vs 3%, P
      < 0.01). Furthermore, compared with moderate Re- segments, a significantly higher
      percentage of severe Re- segments showed a severe reduction of WTI (86% vs 48%, P
      < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588941
TI  - Three-dimensional visualisation of the large bowel: a potential tool for
      assessing targeted drug delivery and colonic pathology.
AB  - A study has been undertaken to assess the feasibility of three-dimensional
      imaging of the dispersion of a non-absorbable tracer released into the colon of
      normal subjects. Six healthy volunteers were selected who were participating in a
      scintigraphic study designed to assess the spreading of 1 MBq indium-111
      Amberlite resin delivered from a delayed capsule system targeted to release in
      the ascending colon. In each case subjects were imaged using a rotating gamma
      camera over a data collection period of approximately 20 min. Three-dimensional
      volume rendered images demonstrated good visualisation of the dispersion of the
      tracer throughout the ascending, transverse and descending colon and provided
      good anatomical visualisation of the shape of the colon, not previously apparent
      from the planar views. The present study demonstrates for the first time, the
      successful three-dimensional imaging of a radiolabelled tracer dispersed
      throughout the colon and opens up the prospects for more detailed study of
      quantification of the volume and distribution of tracers contained within the
      colon.

PMID- 7588940
TI  - A comparison of resting images from two myocardial perfusion tracers.
AB  - We have compared stress-redistribution and delayed rest thallium-201 with rest
      technetium-99m methoxyisobutylisonitrile (MIBI) tomograms in order to compare the
      tracers for the assessment of myocardial viability and to validate a rapid
      protocol combining the two tracers. We studied 30 consecutive patients with known
      or suspected coronary artery disease [group 1: 16 with normal left ventricular
      function, mean left ventricular ejection fraction (LVEF) 55%, SD 6%; group 2: 14
      with abnormal function, mean LVEF 28%, SD 8%]. 201Tl was injected during infusion
      of adenosine followed by acquisition of conventional stress and redistribution
      tomograms. On a separate day, 201Tl was injected at rest with imaging 4 h later.
      99mTc-MIBI was then given at rest and imaging was performed. Three images were
      compared: redistribution 201Tl, rest 201Tl, and rest 99mTc-MIBI. Tracer activity
      was classified visually and quantitatively in nine segments and segments with >
      50% activity were defined as containing clinically significant viable myocardium.
      Mean (+/- SD) global tracer uptake as a percentage of maximum was similar in
      group 1 (rest 201Tl 69% +/- 12%, redistribution 201Tl 69% +/- 15%, rest 99mTc
      MIBI 70% +/- 13%, ANOVA P > 0.05), but in group 2 mean tracer uptake was
      significantly greater in the rest 201Tl images (59% +/- 16%) than in
      redistribution 201Tl images (53% +/- 17%) or rest 99mTc-MIBI images (53% +/- 19%)
      (ANOVA P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588944
TI  - Detection of cervical metastases of thyroid medullary carcinoma by MoAb anti-CEA
      scintigraphy and immunohistochemistry.
AB  - Four patients with medullary thyroid carcinoma (MTC) were examined using anti
      carcinoembryonic antigen (CEA) scintigraphy. Two patients had positive and two
      normal scintigraphic findings, although all the patients had elevated blood test
      markers (calcitonin or CEA). One patient with clinical suspicion of MTC
      metastases had only a faintly positive anti-CEA image, although single-photon
      emission tomographic scanning was used to increase the sensitivity and resolution
      of the method. Therefore, digital image processing of the planar images was
      performed to obtain more detailed information. The analysis revealed distinct
      accumulation of the activity at the right side of the neck at 20 h post
      administration. The specificity of the antibody binding in the malignant cells
      was confirmed after surgery by immunohistochemical staining of the tumour
      specimens for CEA. Both conventional and confocal laser scanning microscopy
      revealed distinct positive staining, indicating that the results obtained from
      the anti-CEA scanning showed specific binding of the labelled antibody in the
      neoplastic tissue.

PMID- 7588945
TI  - Gallium uptake in cerebrotendinous xanthomatosis.
AB  - In a patient with cerebrotendinous xanthomatosis, a rare familial sterol storage
      disease, increased uptake of gallium-67 was observed in the tendon xanthomas.
      This is considered to have resulted from the tumour-like proliferation of
      histiocytic cells in the xanthomas. Abnormalities in the white matter of the
      cerebellum and the brain stem observed by X-ray computed tomography and magnetic
      resonance imaging were not detected by 67Ga scintigraphy, possibly due to the
      small size of the CNS lesions.

PMID- 7588942
TI  - Upregulation of granulocyte CD11b (CR 3) after labelling with technetium-99m
      hexamethylpropylene amine oxime.
AB  - Today technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) is widely used
      for leucocyte scintigraphy, as 99mTc-HMPAO selectively labels granulocytes in
      mixed leucocyte suspensions. However, the influence of cell labelling on the
      expression of specific adhesion proteins has not been studied before. Therefore,
      we investigated five patients, four of whom had established Crohn's disease. We
      found that leucocyte labelling with 99mTc-HMPAO induces increased expression of
      the glucoprotein receptor CD11b on granulocytes, but it is not clear whether this
      upregulation affects the functional integrity of the granulocytes.

PMID- 7588946
TI  - 18FDG PET and acetazolamide-enhanced 99mTc-HMPAO SPET in systemic lupus
      erythematosus.
AB  - In systemic lupus erythematosus (SLE), brain and kidney are the most frequently
      affected organs. Measurements of cerebral blood flow and metabolism by means of
      positron emission tomography (PET) and single-photon emission tomography (SPET)
      can contribute to the diagnostic assessment of the involvement of the central
      nervous system (CNS) in SLE. Functional imaging has been proven to be more
      sensitive than morphological imaging (magnetic resonance imaging and computed
      tomography). In this report, we present the case of a 70-year-old female patient,
      suffering from SLE without symptoms of CNS involvement. In addition to a SPET
      study using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and a
      PET scan with fluorine-18 deoxyglucose (18FDG), a SPET study after acetazolamide
      injection was performed in order to assess the cerebral perfusion reserve. While
      the PET scan showed no major abnormalities, and the baseline SPET study revealed
      only minor changes, the acetazolamide-enhanced SPET study revealed a marked
      reduction of the cortical perfusion reserve, particularly in both frontal lobes.
      It is concluded that "preclinical" CNS involvement, mainly caused by pathological
      mechanisms involving the cerebral blood vessels, can be considered to exist in
      this patient with SLE.

PMID- 7588947
TI  - Tissue retention of indium-labelled antibodies.

PMID- 7588943
TI  - Multimodality imaging of osteomyelitis.
AB  - Early diagnosis of osteomyelitis continues to be a clinical problem. Multiple
      imaging modalities are being used for the diagnosis of osteomyelitis, but none of
      them is ideal for all cases. The choice of modality depends on several factors
      based on an understanding of the pathophysiologic aspects of different forms of
      osteomyelitis. After a brief introduction outlining some basic principles
      regarding the diagnosis of osteomyelitis, pathophysiologic aspects are reviewed.
      Advantages and disadvantages of each imaging modality and their applications in
      different forms of osteomyelitis are discussed. The use of different imaging
      modalities in the diagnosis of special forms of osteomyelitis, including chronic,
      diabetic foot, and vertebral osteomyelitis, and osteomyelitis associated with
      orthopedic appliances and sickle cell disease is reviewed. Taking into account
      the site of suspected osteomyelitis and the presence or absence of underlying
      pathologic changes and their nature, an algorithm summarizing the use of various
      imaging modalities in the diagnosis of osteomyelitis is presented.

PMID- 7588951
TI  - A survey of radiation synovectomy in Europe, 1991-1993.
AB  - The prevalence of radiation synovectomy practice is unknown. As new particulate
      radiopharmaceuticals offering many potential advantages are being developed, it
      seems prudent to appraise the extent, frequency and variation in radiation
      synovectomy practice. We have evaluated radiation synovectomy practice in Europe
      over the period 1991-1993 by means of a postal questionnaire. More than 2300
      European members of the European Association of Nuclear Medicine were questioned
      about the number of treated patients and joints, disease prevalence in their
      patients and the use of radiopharmaceuticals. Overall, 119/490 (24%) of centres
      replying to the survey practised radiation synovectomy during the 3 years. There
      were 13,450 different joint injections in 8578 patients. Rheumatoid arthritis was
      the most prevalent disease in patients treated (71%) and the most frequently
      treated joints were knee (46%) and finger joints (20%). Eight different
      radiopharmaceuticals were employed. Yttrium-90 colloids were most frequently and
      widely (100/119 centres) used, mainly employed for knee synovectomy but were also
      used to treat most appendicular joints. Erbium-169 colloid was almost exclusively
      used to treat finger joints (31/33 centres). Corticosteroid was routinely co
      injected in 36/60 (60%) centres. Radiation synovectomy was widely practised
      throughout Europe during 1991-1993. There are variations in practice illustrated
      by the diversity of treated arthritides and injected joints and by the use and
      application of different radiopharmaceuticals.

PMID- 7588950
TI  - Keeping abreast of time.

PMID- 7588952
TI  - Beta-particle dosimetry in radiation synovectomy.
AB  - Beta-particle dosimetry of various radionuclides used in the treatment of
      rheumatoid arthritis was estimated using Monte Carlo radiation transport
      simulation coupled with experiments using reactor-produced radionuclides and
      radiachromic film dosimeters inserted into joint phantoms and the knees of
      cadavers. Results are presented as absorbed dose factors (cGy-cm2/MBq-s) versus
      depth in a mathematical model of the rheumatoid joint which includes regions of
      bone, articular cartilage, joint capsule, and tissue (synovium) found in all
      synovial joints. The factors can be used to estimate absorbed dose and dose rate
      distributions in treated joints. In particular, guidance is provided for those
      interested in (a) a given radionuclide's therapeutic range, (b) the amount of
      radioactivity to administer on a case-by-case basis, (c) the expected therapeutic
      dose to synovium, and (d) the radiation dose imparted to other, nontarget
      components in the joint, including bone and articular cartilage.

PMID- 7588949
TI  - Radionuclide renal imaging in the United States.

PMID- 7588953
TI  - Serum albumin (SA) accumulation by bronchogenic tumours: a tracer technique may
      help with patient selection for SA-delivered chemotherapy.
AB  - Systemic toxicity and inadequate tumour uptake of chemotherapeutic agents limit
      effective therapy of disseminated malignant disease. We seek to use
      macromolecules for improved delivery of therapeutic agents to tumours, and hope
      to use radiotracer procedures to identify those malignancies able to accumulate
      the transport molecule. A literature search identified in vitro and animal
      experimental data which indicated that serum albumin is taken up in malignancies.
      Selected cytostatic drugs can be bound to albumin, which suggests the suitability
      of the molecule as a potential transport vehicle. We therefore evaluated indium
      111 labelled human serum albumin (HSA) to determine the frequency of its
      accumulation in bronchogenic tumours. Single-photon emission tomographic (SPET)
      images were obtained in 23 patients 48 h after intravenous injection of 1.5 mCi
      111In diethylenetriamine penta-acetic acid (DTPA)-HSA. SPET imaging with
      technetium-99m labelled erythrocytes was included in the protocol to assess the
      influence which vascularity has on the HSA-based images. All patients went on to
      surgery. We documented the histological diagnosis, T-stage and differentiation
      grade. The scintigraphic examination demonstrated HSA uptake in three squamous
      cell carcinomas and four adenocarcinomas. Of these, six malignancies accumulating
      HSA had 2.2-5.4 times, the tracer concentrations observed in comparable
      background regions. Small cell carcinoma failed to accumulate the labelled HSA
      during the 2-day scintigraphic evaluation. The HSA images did not appear to
      represent tumour vascularity. T-stage and differentiation grade failed to predict
      which tumours would demonstrate HSA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588948
TI  - Secretion of [131I]iodide in breast milk and infant dosimetry resulting from the
      administration of [131I]meta-iodobenzylguanidine.

PMID- 7588954
TI  - Preparation of mono-radioiodinated tracers for study of the in vivo metabolism of
      atrial natriuretic peptide in humans.
AB  - In the present paper we evaluate the optimum chemical conditions for labelling
      atrial natriuretic peptide (ANP) and its metabolites and for preparing highly
      purified radiotracers which can be used for in vivo kinetic studies of ANP in
      humans. Synthetic alpha h1-28ANP and some hormone metabolites were iodinated with
      Na125I or Na131I by means of the lactoperoxidase (ANP) or the chloramine-T (ANP
      metabolites) technique. The biological activity of labelled ANP was tested by
      means of a binding study using mouse cardiac membranes. A high-performance liquid
      chromatography (HPLC) procedure was used to purify the labelled hormone and the
      principal labelled metabolites in venous plasma samples collected up to 50 min
      after the injection of 125I-labelled ANP from nine healthy men. The main ANP
      kinetic parameters were derived from the disappearance curves of the [125I]ANP,
      which were satisfactorily fitted by a biexponential function in all subjects. The
      main advantages of this tracer technique are: (1) high accuracy, allowing the
      identification of the metabolites produced in vivo under steady-state conditions
      after injection of the precursor (labelled hormone); (2) high sensitivity,
      allowing the detection of minimal quantities of metabolites (that cannot be
      identified on the basis of the integrated areas from the ultraviolet-absorbing
      peaks on HPLC); (3) high specificity, allowing the detection of possible in vitro
      artefactual generation of cleavage products of ANP using an internal labelled
      standard. Utilizing this tracer method, it was possible to estimate the principal
      parameters of ANP kinetics and also to plot the appearance curves of the labelled
      metabolites produced in vivo after the injection of the labelled precursor.

PMID- 7588955
TI  - West Berlin's contributions to neonatology after World War II.

PMID- 7588961
TI  - Dumping syndrome in a young child.
AB  - We describe a 17-month-old child with dumping syndrome after plication of the
      right diaphragm. He presented with periods of abdominal distension and pallor,
      recurrent convulsions, glucosuria and refusal of feeding. After changing the diet
      the symptoms disappeared. CONCLUSION: Although dumping syndrome in children is
      rare, early recognition is important. Serial determination of blood glucose after
      bolus feeding can lead to the diagnosis. Treatment should consist of dietary
      changes.

PMID- 7588959
TI  - Rapid occurrence of thelarche and menarche induced by hydrocortisone in a teenage
      girl with previously untreated congenital adrenal hyperplasia.
AB  - A 14-year-old girl with untreated simple virilizing congenital adrenal
      hyperplasia presented with absent breast development. She had not had menarche.
      During treatment with hydrocortisone, breasts progressed from Tanner stage one to
      three within 6 months and menarche occurred after 10 months. However, a 1.5 cm
      pituitary adenoma, later described as unspecific pituitary enlargement, remained
      unchanged. CONCLUSION: In a female with untreated congenital adrenal hyperplasia
      and an adult bone age, signs of puberty appeared very rapidly once appropriate
      treatment had begun. This was supposedly due to the declining androgen secretion
      from the adrenals and the release of their restraining action on the hypothalamic
      pituitary ovarian axis.

PMID- 7588958
TI  - Screening for congenital hypothyroidism in Turkey.
AB  - A pilot study was performed to determine the incidence of congenital
      hypothyroidism (CH) in Turkey and to build a model for nationwide screening. From
      December 1991 to December 1992, 30,097 newborns were screened for CH using a
      primary measurement of thyroid stimulating hormone in capillary blood on days 3-5
      of life. Samples were obtained in collaboration with the ongoing nationwide
      phenylketonuria screening programme. Eleven cases of primary CH were detected
      giving the incidence of 1:2736. Recall rate was 2.3%. Replacement therapy with L
      thyroxine was started after the confirmation of diagnosis. The median age at the
      initiation of replacement therapy was 23 days (range 7-35 days). CONCLUSION: The
      incidence of CH is notably higher in Turkey than reported in most other
      countries. Iodine deficiency and/or dyshormonogenesis might contribute to this
      high incidence. This result emphasizes the necessity of a nationwide screening
      programme.

PMID- 7588957
TI  - Disproportionate growth following long-term growth hormone treatment in short
      children with X-linked hypophosphataemia.
AB  - Three short prepubertal children with X-linked hypophosphataemia were treated
      with 1 IU recombinant human growth hormone (rhGH)/kg per week sc in addition to
      calcitriol and phosphate supplementation over a period of 3 years. Improvement of
      height standard deviation score (SDS) ranged from 1.0-1.7 SD based on an increase
      in sitting height of 1.5-2.9 SD, whereas subischial leg length improved only
      slightly by 0.3-0.9 SD. In all three patients, renal phosphate threshold
      concentration increased slightly and transient hyperparathyroidism was noted.
      CONCLUSION: Treatment of stunted children with X-linked hypophosphataemia is
      effective in improving growth velocity, but appears to aggravate the pre-existent
      disproportionate stature of such children.

PMID- 7588956
TI  - Histiocytoses.
AB  - Childhood histiocytoses are a rare and diverse group of histiocytic disorders.
      This review will focus on clinical, pathological and immunopathological features
      of these syndromes. The pathogenesis of Langerhans' cell histiocytosis or class I
      histiocytosis, a proliferative disorder of the Langerhans' cell, remains
      enigmatic. Approaches to treatment are as varied as the clinical presentations,
      ranging from a fatal leukaemia-like disorder to solitary lytic lesions of bone.
      Recent findings indicate that Langerhans' cell histiocytosis is a clonal
      histiocytic disease. The two major class II histiocytoses are familial
      erythrophagocytic lymphohistiocytosis and the reactive haemophagocytic syndromes.
      The clinicopathological similarities between these two entities suggest that they
      share a common immunological feature in which uncontrolled cytokine release from
      activated T-cells leads macrophages to a haemophagocytosing state.

PMID- 7588960
TI  - Complications of percutaneous liver biopsy in infants and children.
AB  - In this study, 144 consecutive percutaneous liver biopsies performed with a 1.6
      mm Menghini needle, during a 2-year period were reviewed. All the children were
      aged under 15 years, 57 patients less than 1 year and 87 more than 1 year. All
      biopsies were adequate and the mean number of portal tracts examined was 17.6 per
      biopsy (14.3 in patients weighing less than 10 kg and 19.1 in the others). There
      were no deaths and we observed only bleeding complications. In patients with
      normal coagulation (128 cases), 1 bleeding requiring transfusion occurred; and in
      patients with abnormal coagulation (16 cases), we observed 2 bleeding cases
      requiring transfusion. CONCLUSION: Percutaneous liver biopsy can be performed
      with 1.6 mm needles in children. For increased safety, ultrasound-guided biopsies
      are recommended.

PMID- 7588962
TI  - Final height and predicted height in boys with untreated constitutional growth
      delay.
AB  - We report on 49 boys with constitutional growth delay (CGD) who were initially
      seen in our clinic at a mean chronological age of 13.3 years (range, 7.3-16.4)
      and a bone age of 11.1 years (range, 6.0-13.5). All were below the 5th height
      percentile for chronological age. A positive family history with delayed growth
      and puberty in one or both parents could be elicited in 75%. All 49 patients were
      re-examined at a mean age of 22.9 years (range, 20.4-31.2). Measured final height
      was 171.3 cm (range, 161.2-181.7), which was slightly, but significantly lower
      than mean target height of 173.0 cm. Final height expressed as standard deviation
      score (SDS) of a male adult population standard was -1.0 (range, -2.4 to 5), also
      significantly lower than initial height SDS related to bone age (SDSBA) of -0.5
      (range, -1.6 to 2). If related to target height (Tanner), final height was found
      to correlate positively with the initial bone age deficit and the initial height
      SDSBA. Observed final height was also compared with the predicted adult height by
      the methods of Bayley-Pinneau (BP), Tanner-Whitehouse Mark II (TW II) and Roche
      Wainer-Thissen. Regression equations between all three prediction methods and
      final height showed an excellent correlation (P < 0.0001). However, only by the
      BP method was predicted height very close to and no different from measured final
      height (paired t-test). Despite this, final height in 16 of 49 patients (32.6%)
      differed by more than 5.0 cm from BP predicted height.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7588963
TI  - Kawasaki disease associated with parvovirus B19 infection.
AB  - In a 9-week-old boy with Kawasaki disease an active parvovirus B19 infection was
      diagnosed serologically. CONCLUSION: This case supports the hypothesis of an
      aetiological relationship between parvovirus B19 infection and Kawasaki disease.

PMID- 7588964
TI  - Congenital toxoplasmosis: 10-year follow up.
AB  - A long-term follow up was begun in 1982 on offspring of mothers who acquired
      toxoplasmosis during gestation. The 114 newborns were subdivided into 3 groups:
      (1) 26 born to mothers with certain infection; (2) 51 born to mothers with
      probable infection, and (3) 37 born to mothers with doubtful infection. There
      were five infections in the first group (19.2%), three in the second (5.8%) and
      none in the third. For purposes of data elaboration we considered only the 77
      offspring of mothers with certain or probable infection. Of these, 2 infected
      cases out of 52 (3.8%) were born to mothers with infection in the first trimester
      of pregnancy, 4 out of 21 (19%) in the second trimester, and two out of four in
      the third. There were a total of 8 congenital infections (10.4%). Specific IgM
      antibodies were revealed in five out of eight infected children (62.5%).
      Infection was symptomatic in two children (2.6% of newborns at risk, 25% of
      infected cases), both born to mothers with infection in the second trimester. In
      the other six cases diagnosis was reached by evaluating trends in antibody
      levels: the percentage of infected newborns was higher in the group of maternal
      infections untreated (50%) or improperly treated (15.4%), compared to those
      receiving adequate treatment (6.9%). We suggest considering as infected children
      presenting specific IgM antibodies and/or antibody titres which do not become
      negative, even when symptoms are absent. Therapy with spiramycin should be
      started in all newborns at risk, while the use of sulphamides and pyrimethamine
      is justified only after the presence of infection is confirmed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7588965
TI  - Recurrent suppurative thyroiditis due to pyriform sinus fistula: a case report.
AB  - Acute suppurative thyroiditis is a rare disease, particularly in childhood. We
      present a case with recurrent acute suppurative thyroiditis due to a pyriform
      sinus fistula originating from the fourth branchial pouch. The typical symptoms
      of a pyriform sinus fistula are recurrent left-sided pain and swelling of the
      neck with signs of acute bacterial inflammation. Diagnosis should be made by high
      resolution ultrasound, barium meal studies and endoscopic examination. During
      acute exacerbations treatment with antibiotics is indicated, but permanent cure
      can only be attained by complete fistulectomy.

PMID- 7588966
TI  - A family with combined Farber and Sandhoff, isolated Sandhoff and isolated fetal
      Farber disease: postnatal exclusion and prenatal diagnosis of Farber disease
      using lipid loading tests on intact cultured cells.
AB  - An earlier described patient with combined sphingolipidoses, Farber and Sandhoff
      disease, had two healthy older brothers and two further sibs, one with Sandhoff
      disease and one (a fetus) with Farber disease, showing segregation of the
      respective genes. The prenatal diagnosis in the latter was performed using lipid
      (sphingomyelin and glucosylceramide) loading tests on the cultured amniotic fluid
      cells. After 1-3 days of incubation the cells' lipid extract revealed radioactive
      ceramide to be released and highly accumulated. The deficiency in acid ceramidase
      was known from the patient with the combined diseases. Confirmation of the
      prenatal Farber diagnosis was done by similar loading tests on the fetal
      fibroblasts and by analysis of liver lipids of the less than 18-week-old fetus.
      CONCLUSION: This is the first report on the use of lipid loading tests on intact
      cultured cells for prenatal diagnosis of Farber disease. The postnatal diagnosis
      of Farber disease can also be readily made using those tests, as was shown in
      four further cases.

PMID- 7588968
TI  - Fetal brain disruption sequence in sisters.
AB  - We report two female siblings with the fetal brain disruption sequence. Extensive
      investigation of both children failed to define a definitive aetiology but
      clinical and laboratory findings are consistent with a hitherto unknown storage
      disease. We postulate that the accumulation of a neurotoxic metabolite may be
      responsible for the disease phenotype observed. This is the first report of
      recurrence of the fetal brain disruption sequence and supports the existence of a
      genetic form of this condition. Previous reports have emphasized possible
      environmental aetiologies. Infants with fetal brain disruption sequence should be
      investigated exhaustively and, in the absence of definitive evidence of an
      environmental cause, the possibility of a genetic aetiology should be considered.
      In some families the recurrence risk may be as high as one in four.

PMID- 7588969
TI  - Floating-Harbor syndrome: description of a further patient, review of the
      literature, and suggestion of autosomal dominant inheritance.
AB  - The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone
      age, speech development, and typical facial features. The face is triangular with
      deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and
      thin lips. We present an additional patient and review 16 cases from the
      literature. The possible phenotype in the patient's mother suggests a dominant
      mode of inheritance for the syndrome. CONCLUSION: The Floating Harbor syndrome is
      a growth deficiency syndrome characterized by proportionate short stature,
      characteristic face and delayed speech development. Inheritance is possibly
      autosomal dominant.

PMID- 7588967
TI  - Ketamine and strychnine treatment of an infant with nonketotic hyperglycinaemia.
AB  - Non-ketotic hyperglycinaemia (NKH) is a severe seizure disorder associated with
      high glycine levels. Glycine is a major inhibitory neurotransmitter in the CNS,
      but has also modulating effects at one of the glutamate receptors, the N-methyl-D
      aspartate-(NMDA) receptor. Based on this knowledge we treated a female newborn
      suffering from severe NKH with the NMDA receptor blocker ketamine in association
      with strychnine and magnesium supplementation. This treatment led to cessation of
      seizures, reappearance of swallowing and sucking and improved the neurological
      status. Some pharmacokinetic data of strychnine and ketamine in the infant are
      given. CONCLUSION: Ketamine in combination with strychnine may be beneficial in
      non-ketotic hyperglycinaemia.

PMID- 7588970
TI  - Effects of bilirubin on visual evoked potentials in term infants.
AB  - To determine bilirubin-induced neurotoxicity, serial visual evoked potentials
      (VEPs) of 72 infants with neonatal hyperbilirubinaemia and 22 controls were
      evaluated and compared in four sessions for 8 weeks after birth. The levels of
      maximal serum bilirubin were found positively related to the wave latencies of
      first VEP. Within 8 weeks after birth, the wave latencies were significantly
      prolonged in infants in the severe and moderate groups than in the controls. The
      amplitudes of VEPs were apparently lower in severe and moderate groups than in
      the control group only in the 1st week after birth. At 1 year, 4 of the 18
      infants in the severe group had poor motor skills and one had general hypotonia.
      CONCLUSION: These results suggest that bilirubin may affect the visual pathways,
      and that VEP is a useful adjunct to the neurological assessment of neonatal
      hyperbilirubinaemia.

PMID- 7588971
TI  - Transient foramen ovale incompetence in the normal newborn: an echocardiographic
      study.
AB  - To assess presence, predominant direction and natural history of interatrial
      shunt flow in the normal newborn period an uncontrolled pilot study was
      performed. Twenty term ( > 36 completed weeks gestational age) newborns were
      studied using cross sectional, M-mode and colour Doppler echocardiography;
      cardiac, pulmonary or renal disease were excluded before entry to the study. In
      11 of 20 normal term newborns a predominant left to right interatrial shunt was
      detected on the 1st day after birth. This shunting, taking place in ventricular
      systole, disappeared in 10 cases during the first 6 postnatal days and in 1 case
      after 6 weeks. No relation was found between the presence of an atrial left to
      right shunt and gestational age or patency of the ductus arteriosus. CONCLUSION:
      We conclude that interatrial left to right shunting is common in half of the
      normal newborns (95% confidence interval 31.5%-76.9%), during the first 6 days of
      extra-uterine life. Our findings may be explained by a transient period of
      physiological expansion of extracellular volume in the newborn, resulting in
      slight atrial stretch, and this in combination with a relatively short foramen
      ovale flap.

PMID- 7588974
TI  - Rodent carcinogens in human food: are they important?

PMID- 7588972
TI  - Paediatrician attendance at caesarean section.
AB  - Five hundred and twenty term singleton infants delivered by Caesarean section
      were categorised into six groups according to type of Caesarean section (elective
      or emergency), type of anaesthesia (epidural or general) and presence of fetal
      distress. Infants delivered under general anaesthesia had a significantly higher
      incidence of respiratory depression at birth with Apgar scores < 7 at both 1 and
      5 min (P < 0.00001), greater need for active resuscitation (intermittent positive
      pressure ventilation or bag and mask ventilation) (P < 0.000001) and a higher
      rate of neonatal unit admission (P < 0.00001). Caesarean sections for fetal
      distress were associated with a significantly higher incidence of intermittent
      positive pressure ventilation, but not bag and mask ventilation, for both the
      general anaesthesia and epidural groups (P < 0.003 and P < 0.02 respectively),
      indicating severe respiratory depression in some cases. Under epidural
      anaesthesia, both elective section and emergency section without fetal distress
      were low risk deliveries. By excluding the non-cephalic presentation cases in
      these two groups, the incidence of infants requiring active resuscitation was
      equivalent to the incidence quoted for spontaneous normal delivery. CONCLUSION:
      Attendance by a paediatrician is not routinely required at epidural Caesarean
      section when the infant is cephalic and when there is no fetal distress. Every
      effort should be made to ensure that epidural anaesthesia is provided in
      preference to general anaesthesia.

PMID- 7588975
TI  - L-carnitine: a way to decrease cellular toxicity of ifosfamide?

PMID- 7588973
TI  - The social effects in adult life of chronic physical illness since childhood.
AB  - An unselected group of 487 (222 females, 265 males) patients with juvenile onset
      chronic physical disorders was studied at the age of 19-25 years for their social
      outcome and compared with an age-matched group of 202 physically healthy
      controls. The interview covered both comprehensive and vocational schooling, data
      on their employment status, relationship to parents and sexual development in
      detail. The overall social maturation index showed poor social maturation in
      patients more often than in the controls. At the time of the study 23% of the
      patients and 11% of the controls had no vocational education or were not on their
      way to gaining it. Excluding those with a disability pension (10%), working
      experience, employment status and unemployment were fairly similar in both
      groups. Sexual development was delayed more often in the patients than in the
      controls and the patients were significantly more often unmarried and living in
      the same household as their parents. However, social and psychological factors
      accumulating in excess in the patient group were observed more significant than
      the physical disease to the delayed social maturation. CONCLUSION: Among patients
      with chronic physical disorders there is a minor group with delayed social
      maturation. Those at risk can easily be recognized even before adolescence in
      order to offer them and their parents support to achieve reasonable social
      development in early adulthood.

PMID- 7588976
TI  - Corticosteroid and hypercoagulability.

PMID- 7588978
TI  - Gianotti-Crosti syndrome as a result of vaccination and Epstein-Barr virus
      infection.

PMID- 7588977
TI  - Full triploidy in a liveborn preterm infant.

PMID- 7588980
TI  - Clinical signs of mosaicism.

PMID- 7588979
TI  - Studies with pre-treatment of milk with calcium acetata to reduce the phosphate
      content.

PMID- 7588981
TI  - Improved understanding of respiratory control--implications for the treatment of
      apnoea.
AB  - Recurrent apnoea of prematurity should probably be regarded as more or less a
      physiological phenomenon providing that it is not precipitated by for example
      septicaemia and cerebral haemorrhage since the fetus of the corresponding age is
      only breathing episodically. Neonatal apnoea is probably not caused by a
      deficient respiratory rhythmic regeneration, but rather by respiratory inhibitory
      mechanisms induced by hyperthermia, hypoxia and adenosine. A more physiological
      approach should be taken in the treatment of apnoea. Some warning against the
      extensive use of xanthine derivatives should be raised.

PMID- 7588985
TI  - Surfactant replacement therapy for non-respiratory distress syndrome neonatal
      respiratory disease--research or clinical application?
AB  - Research studies have highlighted both physiological and pathological evidence to
      incriminate surfactant abnormality and/or deficiency in many neonatal respiratory
      diseases. Data from animal models and clinical studies support the concept that
      surfactant replacement therapy (SRT) may have a role to play in such problems.
      There is now, therefore, a need to perform further randomized controlled trials
      to assess the appropriate clinical application of SRT in non-respiratory distress
      syndrome neonatal respiratory disease.

PMID- 7588982
TI  - Recombinant haemopoietic growth factors in the newborn--will they be useful?
AB  - In vivo, realisation of the physiological reserve capacity of haemopoiesis
      depends on stimulation by cytokines, growth factors produced by autologous blood
      mononuclear cells. These cytokines include erythropoietin, granulocyte/macrophage
      colony stimulating factors, and thrombopoietin. In preterm infants, inadequate
      haemopoietic growth factor production limits haemopoiesis in its response to
      demands for extra blood cell production in stress situations. Haemopoiesis may
      also be inhibited by inflammatory disease and by nutritional deficiencies. In
      infants in intensive care, losses of blood, which contain haemopoietic stem cells
      and other progenitors, may also impair blood cell production. Recombinant
      haemopoietic growth factors promise to prevent or correct in part, this
      haemopoietic inadequacy. Verification of their therapeutic roles depends on
      further improvements in management of the preterm infant. These improvements
      include the optimisation of nutritional support and, especially, in terms of the
      endowment of blood from the placenta at birth, which strongly influences clinical
      outcome.

PMID- 7588984
TI  - Near infrared spectroscopy.
AB  - Near infrared spectroscopy is a novel technique still at an early stage in its
      development. Current technology has been used to measure cerebral haemodynamics
      and oxygenation at the cotside in sick preterm infants, to observe cerebral
      oxygenation during birth, and in other situations such as cardiac surgery. At
      present it is best regarded as a research technique.

PMID- 7588986
TI  - Pain relief and sedation during neonatal intensive care.

PMID- 7588987
TI  - How does exogenous surfactant really work?
AB  - The finding of a lag of up to 24 h between the response to exogenous surfactant
      in infants with respiratory disease syndrome as assessed by blood gases and
      improvements in respiratory system compliance has generated considerable
      interest. Studies have shown that there is rapid increase in functional residual
      capacity after natural surfactant and a less dramatic rise in effective pulmonary
      blood flow. These changes in blood flow are not associated with a sustained fall
      in pulmonary artery flow or pressure indicating that the main improvement in
      oxygenation results from a reduction in intrapulmonary shunting. Recent studies
      have shown that natural surfactant does produce rapid increases in lung
      compliance but only if the expired gases are vented to ambient rather than to
      positive end expiratory pressures. Thus the mechanical effects of natural
      surfactant are initially largely limited to the part of the tidal volume which is
      close to the functional residual capacity.

PMID- 7588988
TI  - Antenatal lung maturation--should we all be using thyrotropin-releasing hormone?
AB  - Thyrotropin-releasing hormone (TRH) appears to be a promising antenatal therapy
      to help reduce neonatal lung disease. Clinical trials, however, show differing
      results. At present the optimum dosage, frequency and method of administration
      have not been established. TRH has been shown significantly to elevate blood
      pressure in patients with preeclampsia suggesting it should not be used in this
      group. Moreover concerns over its use in growth retarded fetuses and its long
      term neonatal effects have not been addressed. Further trials are needed before
      routine clinical use can be recommended.

PMID- 7588983
TI  - Appropriate fluid regimens to prevent bronchopulmonary dysplasia.
AB  - Pulmonary oedema is an important problem in premature neonates with surfactant
      deficiency because of fluid accumulation in the lung interstitium and reduced
      urine output. Some retrospective reports suggest that excessive early hydration
      might increase the risk of bronchopulmonary dysplasia (BPD). Only three
      prospective studies evaluating low or conventional fluid administration regimens
      to very low birth weight infants have been published. According to their results
      no significant differences in the incidence of BPD have been shown. However,
      fluid restriction seems to improve the outcome of the infants because of
      decreased incidence of haemodynamically significant patent ductus arteriosus,
      necrotizing enterocolitis, pulmonary air leaks and decreased mortality. The
      appropriate amount of sodium in the intravenous fluids during the first days of
      life needs further evaluation. In tiny infants with birth weights from 500 to
      800g intensive monitoring of fluid balance is essential to control the extremely
      high fluid losses due to evaporation. Undernutrition is a risk factor of BPD and
      therefore it is important to start parenteral nutrition early. The benefit of the
      use of colloids as volume expanders is controversial. According to some
      retrospective reports there might be an association with increased use of
      colloidal fluids during the first days of life and the development of BPD. Early
      excessive fluid administration might constitute a potential risk for low birth
      weight infants with hyaline membrane disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7588989
TI  - The cost benefit ratio of enantiomeric drugs.
AB  - Several drugs possess a chiral structure, i.e. they contain one or more
      stereogenic centres in their molecule. While naturally occurring active
      principles usually contain a single enantiomer, most chiral drugs produced by
      chemical synthesis are used in the form of racemic mixtures of two or more
      diastereoisomers. These stereoisomers (including enantiomers) may interact in
      different ways with biological structures and, therefore, may exhibit widely
      different pharmacokinetic properties. In the pharmaceutical industry, partly in
      response to increasing demands raised by regulatory authorities, these
      considerations justify the current trend to develop the single enantiomer
      characterized by the most favourable profile of activity (eutomer). The
      availability of new chemical and analytical technologies facilitates
      stereoselective synthetic processes and separation of individual enantiomers from
      racemic mixtures. Any decision to develop a drug as a single enantiomer, however,
      should be made only after careful evaluation of the cost-benefit ratio, i.e. when
      the advantages of the eutomer in terms of efficacy and tolerability outweigh the
      associated increase in production and development costs with respect to the
      racemic drug. This article takes into consideration synthetic procedures and
      pharmacological profiles for a number of chiral drugs in therapeutic use
      (naproxen, labetalol, and warfarin) or selected for clinical development, such as
      the beta-blocker dilevalol or the mucokinetic agent 3'-hydroxyfarrerol. These
      examples demonstrate that the kinetic, pharmacological and toxicological
      properties of individual enantiomers need to be clearly characterized before any
      decision can be made concerning the development of a chiral drug. The choice of
      preferentially developing a single enantiomer should be based on careful
      consideration of production and development costs and actual therapeutic
      advantages especially in terms of improved safety.

PMID- 7588991
TI  - BIO-international '94 Conference on Bioavailability, Bioequivalence and
      Pharmacokinetic Studies and Pre-Conference Satellite on 'In Vivo/In Vitro
      Correlation'. Munich, Germany, June 14-17, 1994.

PMID- 7588990
TI  - Apomorphine pharmacokinetics in parkinsonism after intranasal and subcutaneous
      application.
AB  - Apomorphine was administered subcutaneously and intranasally to 7 patients
      suffering from Parkinsonism with 'on-off' problems. This comparative
      pharmacokinetic study showed that the two routes of administration are comparable
      with respect to absorption kinetics. Apomorphine is rapidly absorbed when
      administered intranasally or subcutaneously with an absorption half life of 8.6
      min and 5.8 min, respectively. The high rate of absorption is also reflected by
      the time for the plasma concentration to peak (tmax) and the lag times. The tmax
      was 23 min for intranasal route and 18 min for the subcutaneous route while the
      lag times were 2.8 min and 3.9 min, respectively. The bioavailability of
      intranasal apomorphine compared to the subcutaneous route amounted to 45%. After
      intranasal and subcutaneous administrations, the elimination half life of
      apomorphine amounted to 31 min and 27 min, respectively.

PMID- 7588992
TI  - The identification and characterisation of chloramphenicol-aldehyde, a new human
      metabolite of chloramphenicol.
AB  - The toxic aldehyde derivative of chloramphenicol has previously been reported as
      a metabolic product only in the rat. Chloramphenicol-aldehyde has been
      synthesised and characterised and shown to exist in at least two forms, possibly
      due to rearrangement within the molecule. The authenticated compound has been
      used to identify chloramphenicol-aldehyde as a metabolic product excreted in the
      urine of children treated with chloramphenicol.

PMID- 7588993
TI  - Interaction of theophylline and ipriflavone at the cytochrome P450 level.
AB  - The effect of ipriflavone administered at a dose of 25 mg/kg and 100 mg/kg and
      coadministered with theophylline was investigated in selective assays of
      particular P450 isoenzyme activities. Significant changes could be detected in
      the activities of CYP2E1 and CYP3A in liver microsomes from male Wistar rats
      treated with ipriflavone. Induction of CYP2E1 was shown by aniline or p-nitro
      phenol hydroxylation as a result of ipriflavone treatment. Aniline hydroxylation
      activity of CYP2E1 was induced by theophylline + ipriflavone (100 mg/kg)
      coadministration as well. It should be noted that theophylline does not cause
      alteration in CYP2E1 activity. On the other hand, ipriflavone inhibited
      ethylmorphine and aminopyrine N-demethylation activities catalysed by CYP3A. An
      additional effect in the inhibition of aminopyrine N-demethylation could be
      observed in microsomes from theophylline + ipriflavone treated groups. Our
      results suggest that the decrease in theophylline metabolism increasing level of
      serum theophylline of theophylline-treated patient during ipriflavone
      administration [Takahashi J. et al. (1992): Eur. J. Clin. Pharmacol., 43, 207
      208] may be related to CYP3A inhibition by ipriflavone.

PMID- 7588994
TI  - In vivo and in vitro kinetics of mofarotene in mouse, rat, dog and man.
AB  - The pharmacokinetics of mofarotene were investigated in mice, rats and dogs
      following single intravenous and oral administrations. Healthy volunteers were
      also given a single oral dose of 300 mg mofarotene. The data indicate a similar
      disposition for mofarotene in all species studied: low clearance consistent with
      a high bioavailability following oral dosing, and large volume of distribution
      indicating an extensive tissue uptake. Also in vitro in liver microsomes, the
      values for intrinsic clearance were in all species within a 2-fold range. The
      dog, however, tended to exhibit, both in vitro and in vivo, the lowest clearance.
      Although (due to the lack of protein binding data) a direct prediction of the in
      vivo clearance from in vitro data was not possible, the experiments with liver
      microsomes did provide a clear insight into the rate of elimination of mofarotene
      in vivo in the different species studied including man.

PMID- 7588995
TI  - Danggui (Angelica sinensis) affects the pharmacodynamics but not the
      pharmacokinetics of warfarin in rabbits.
AB  - Danggui is a popular traditional Chinese medicinal (TCM) herb which is easily
      obtained by the public. The effects of Danggui on the pharmacokinetics and
      pharmacodynamics of warfarin were studied in rabbits. Single subcutaneous doses
      (2 mg/kg) of warfarin were administered to 6 rabbits with or without 3 days
      treatment with oral Danggui extracts (2 g/kg twice daily). Plasma warfarin
      concentrations were measured by high performance liquid chromatography (HPLC) for
      72 h after each of the two warfarin doses. The prothrombin time (PT) was measured
      daily for 3 days both during the Danggui treatment period and after warfarin
      doses. Danggui treatment did not affect PT on its own, but significantly lowered
      PT values 3 days after co-treatment with single dose warfarin. No significant
      variations in the single dose pharmacokinetic parameters of warfarin were
      observed after Danggui treatment. A separate group of 6 rabbits were given daily
      subcutaneous doses of warfarin (0.6 mg/kg) to achieve steady state level,
      followed by 3 day treatment with oral Danggui extract (2 g/kg twice daily). The
      slight increase in PT was not significant and two rabbits died after day 7 of the
      treatment period. However, there was no significant difference in steady state
      concentrations of warfarin after the Danggui treatment. Results indicate that
      precautionary advice should be given to patients who self-medicate with Danggui
      or other TCM products while on chronic treatment with warfarin.

PMID- 7588996
TI  - Metabolism of levomepromazine in man.
AB  - The phenothiazine drug, levomepromazine (LM), is used in the treatment of
      psychiatric disorders and as an analgesic. A single 50 or 100 mg dose of LM was
      given to healthy male volunteers, and urine samples were collected for 24 h. The
      urine was treated with beta-glucuronidase, purified by solid-phase extraction,
      and analyzed on a GC-MS system for identification of LM metabolites. Mass spectra
      suggesting 14 different LM metabolites were obtained from the samples. Our of
      these, 13 spectra could be ascribed to specific metabolites, 5 of which have not
      previously been identified. All these 5 metabolites were hydroxylated at the
      phenothiazine nucleus. Although the applied method did not determine the
      positions of hydroxyl groups on phenothiazine nuclei. 3 of the 5 metabolites were
      identified as O-desmethyl 3-hydroxy LM, O-desmethyl 7-hydroxy LM, and N,O
      didesmethyl 7-hydroxy LM, based on their chromatographic properties. In addition
      two metabolites, one being hydroxylated on the phenothiazine nucleus, and one
      being O-demethylated and hydroxylated on the nucleus, were found. It is suggested
      that these were 8-hydroxy LM and O-desmethyl 8-hydroxy LM. The concentrations of
      3-hydroxy LM (free+conjugated) appeared to be much higher than the concentrations
      of any other metabolite in the samples.

PMID- 7588998
TI  - Symposium on Electron microscopy. Leipzig, 10-15 September 1995. Abstracts.

PMID- 7589002
TI  - The effect of nicardipine on renal functions following 72-hour cold ischemia.
AB  - The aim of the study was to investigate the cytoprotective effect of a calcium
      channel blocker, nicardipine, on altered renal function due to cold ischemia for
      72 h. The experiments were performed on isolated perfused kidneys from adult
      rabbits. Kidneys were perfused with either standard Euro-Collins (EC) solution (n
      = 7) or EC containing nicardipine (n = 6) and then incubated with the same
      preservation solutions in a beaker exposed to cold ischemia for 72 h at +4
      degrees C. In the control group the same procedure was applied to untreated
      kidneys (n = 6) which were exposed to cold ischemia for 30 min. Vascular
      responses and urinary output to noradrenaline, angiotensin II, endothelin-1,
      acetylcholine and sympathetic stimulation were assessed as the functional
      activities of the kidney. The responses of the preserved kidneys were compared
      following cold ischemic conditions. The results indicate that the addition of
      nicardipine to EC solution protects the vascular endothelial regulatory function
      and urine excretion; therefore, dihydropyridine calcium channel blockers might be
      useful for kidney preservation.

PMID- 7589000
TI  - Effects of N-acetyl-L-cysteine on regional blood flow during endotoxic shock.
AB  - We previously reported that N-acetyl-L-cysteine (NAC), an oxygen free-radical
      scavenger, can increase the oxygen extraction capabilities during endotoxic shock
      when blood flow is progressively reduced. In the present study, we investigated
      whether the protective effects of NAC are related to an improvement in regional
      blood flow following endotoxemia. Fourteen anesthetized, saline-infused and
      ventilated dogs were divided into two groups: 7 dogs received NAC (150 mg/kg,
      followed by a 20 mg/kg.h infusion), and the other 7 dogs served as a control time
      matching group. Thirty minutes later all the dogs received Escherichia coli
      endotoxin (2 mg/kg) i.v. A saline infusion was started 30 min after endotoxin
      challenge to restore pulmonary artery occlusion pressure to baseline and maintain
      it constant. Regional blood flow was measured by ultrasonic volume flowmeter. In
      the control group, arterial pressure, left ventricular stroke work index and
      systemic vascular resistance remained lower than baseline. Mesenteric, renal and
      femoral arterial blood flow increased but only femoral blood flow returned to
      baseline levels. In the NAC group, cardiac index and left ventricular stroke work
      index remained higher and systemic and pulmonary vascular resistance were lower
      than in the control group. Blood flow in mesenteric, renal and especially femoral
      arteries was higher than in the control group. Fractional blood flow increased
      only in the femoral artery. PaO2 and PvO2 had similar courses in the two groups.
      A higher venous admixture was associated with a higher cardiac index and a lower
      pulmonary vascular resistance in the NAC group. Oxygen delivery and oxygen-uptake
      were higher in the NAC-treated than in the control animals throughout the
      study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589001
TI  - Intra-arterial liposomal adriamycin for metastatic adenocarcinoma of the liver.
AB  - A liposome-entrapped liposome form of Adriamycin (Lip-ADM) has been demonstrated
      to cause less myocardial and gastrointestinal toxicity than free ADM. In the
      present study, Lip-ADM prepared by the remote loading method was administered to
      3 patients with metastatic adenocarcinoma of the liver via a reservoir with the
      catheter located in the proper hepatic artery. The primary tumor was gastric
      cancer in 2 patients and sigmoid colon cancer in 1. Lip-ADM was administered at
      doses of 10, 20 or 50 mg per time. The total ADM dose was 170, 490, and 760 mg,
      respectively. No severe adverse effects, such as nausea, vomiting, stomatitis,
      alopecia or cardiotoxicity, were observed in any of the patients. Although mild
      leukocytopenia (2,800/microliters) was observed in 1 patient, anemia or
      thrombocytopenia did not occur. The survival time was respectively 6, 15, and 17
      months from the start of Lip-ADM administration. A partial response was obtained
      in 1 patient and stable disease in 1 patient. Administration of Lip-ADM via a
      reservoir appears to be a useful treatment for patients with metastatic
      adenocarcinoma of the liver, since the low toxicity of this preparation allows an
      increase of the total dose of ADM.

PMID- 7588999
TI  - Allopurinol effects in rat liver transplantation on recovery of energy metabolism
      and free radical-induced damage.
AB  - Rat livers were orthotopically transplanted after 90-min cold ischemia (group 1)
      or after 20-min warm and 70-min cold ischemia without (group 2) or with (group 3)
      allopurinol treatment (AT) (50 mg/kg i.v. 10 min prior to warm ischemia into the
      donor, flush perfusates with 1 mmol/l). Recovery processes were followed up for
      60 min of reperfusion. Liver tissue levels of ATP and total adenine nucleotides
      were restored in group 1 to almost preischemic ranges within 15-30 min, remained
      significantly reduced by 30 and 20%, respectively, in group 2, and recovered with
      AT within 60 min in group 3 to almost the same extent as in group 1. A massive
      increase in the tissue malondialdehyde concentration, indicative of lipid
      peroxidation, occurred in the beginning of reperfusion of warm-ischemically
      damaged donor livers, which in group 3 with AT tended to be less pronounced than
      in group 2 without AT. The GSSG/GSH ratio reflecting intracellular oxidant stress
      averaged 3.3 x 10(-3) in group 1 between 15 and 60 min reperfusion. In group 3 AT
      resulted in comparably low values averaging 3.8 x 10(-3), while in warm
      ischemically damaged livers without AT of group 2 this ratio was significantly
      and continuously elevated averaging 5.8 x 10(-3).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7588997
TI  - Effect of sulfated xylans during the interaction of [125I]-thrombin with
      antithrombin III or heparin cofactor II of human plasma.
AB  - [125I]-Labeled thrombin was incubated with human plasma and its interactions with
      the two plasma protease inhibitors antithrombin III (AT-III) or heparin cofactor
      II (HC-II) were investigated in the presence of oat spelts xylan sulfate (OSXS),
      sodium pentosan polysulfate (SP-54), and the results were compared with heparin
      and dermatan sulfate. Addition of OSXS or SP-54 enhanced the complexation of
      thrombin with HC-II or with both AT-III and HC-II depending upon the
      concentration and the duration of the interactions of the sulfated compounds with
      plasma. During the 30 s interaction, OSXS and SP-54 enhanced both AT-III-thrombin
      and HC-II-thrombin interaction while heparin was more selective and enhanced only
      the AT-III-thrombin interaction. However after a 2 min interaction, heparin
      showed an increase in the HC-II-thrombin interaction at higher concentrations.
      The complexations of AT-III-thrombin and HC-II-thrombin were reversed in the
      presence of 200 micrograms/ml of SP-54 during a 30 s interaction or in presence
      of 100 micrograms/ml of OSXS during a 2 min interaction. The Western blotting
      method of detecting thrombin showed that during the 10 s interaction, heparin
      enhanced the thrombin-AT-III complex formation while OSXS enhanced the thrombin
      HC-II complex formation.

PMID- 7589004
TI  - Effect of sodium nitroprusside on cardiac output during cross-clamping of the
      descending thoracic aorta in pigs.
AB  - Sodium nitroprusside (SNP) is used to control proximal hypertension during cross
      clamping of the descending thoracic aorta (XC). To assess the haemodynamic
      effects of SNP on cardiac output (CO) during XC, 21 pigs were anaesthetized with
      ketamine and fentanyl. In the control group (n = 11), no vasodilating therapy was
      given. In the investigation group (SNP group), 2 animals died during the surgical
      preparation and were excluded, leaving 8 animals in the group (n = 8). In these
      animals, SNP was infused in order to keep the mean arterial pressure (MAP) at
      about 100 mm Hg during cross-clamping. In both groups, aorta was cross-clamped
      for 30 min, and cardiac output (CO) was measured by the thermodilution technique.
      Following cross-clamping, CO increased 107% in the control group and 96% in the
      SNP group. There was an increase in heart rate (HR) of 77% in the control group
      and of 110% in the SNP group, and a reduction in systemic vascular resistance of
      41% in the SNP group. Stroke volume (SV) was unchanged in both groups. MAP
      increased 83% in the control-group. No differences were observed between the two
      groups regarding central venous pressure or pulmonary artery pressure. Four
      animals in the SNP group died 5-10 min after release of the aortic clamp. In
      conclusion, we found equal increase in CO in both groups. The increase in CO was
      related predominantly to increased HR, whereas SV was largely unaltered.
      Vasodilation with SNP increased the mortality following clamp removal in this
      experimental model.

PMID- 7589003
TI  - Experimental study of liver injury after partial hepatectomy with intermittent or
      continuous hepatic vascular occlusion. Differences in tolerance to ischemia
      between normal and cirrhotic livers.
AB  - The degree of residual liver injury in normal and cirrhotic rats undergoing 70%
      hepatectomy with hepatic inflow occlusion was examined. The total duration of
      clamping was 60 min and animals were divided into 3 groups according to the
      ischemic modality: a 15-min intermittent clamping group (group I); a 30-min
      intermittent clamping group (group II), and a 60-min continuous clamping group
      (group III). In normal liver rats, the survival rates after operation in groups
      I, II and III were 90, 90 and 30%, respectively, compared to 70, 50 and 38%,
      respectively, in cirrhotic rats. The serum aspartate aminotransferase (AST) level
      increased markedly with prolongation of each period of clamping in rats with
      normal liver, showing higher AST levels than those with cirrhotic liver. The
      liver tissue adenosine-5'-triphosphate (ATP) levels and energy charge (EC) values
      decreased with prolongation of each period of clamping. Cirrhotic livers showed
      lower ATP levels and EC values than normal livers. Although there was no
      significant difference in the mitochondrial function between normal and cirrhotic
      livers in the group of the same form of ischemia, phosphorylative efficiency of
      mitochondria was maintained satisfactorily in normal groups I and II and in the
      cirrhotic group I. Even though cirrhotic livers showed a smaller necrotic
      response to ischemia than normal livers, they were more vulnerable to ischemia
      because of an inability to maintain energy metabolism. Therefore, when performing
      resection of a cirrhotic liver, a 15-min intermittent clamping method should be
      adopted.

PMID- 7589007
TI  - Does fibrin glue improve drainage after axillary lymph node dissection?
      Prospective and randomized study in humans.
AB  - The aim of this prospective and randomized study was to establish whether the use
      of fibrin glue was beneficial after axillary lymph node dissection. From January
      1990 to January 1991, 40 women were randomized before surgery for breast cancer:
      20 patients (group A) underwent vaporization of fibrin glue (Tissucol, 5 ml of
      500 IU thrombin) only in the area of axillary dissection; another 20 patients
      (group B) served as controls. The two groups were compared for age, number of
      nodes removed and involved, volume and duration of fluid drainage and
      complications. Student's t test, Mann-Whitney nonparametric test and the chi 2
      test were used when appropriate for statistical analysis. The two groups were
      well balanced for age, number of nodes removed and involved, staging and
      histologic findings. The average volume of lymphorrhea in the lymph node
      dissection area was greater after use of fibrin glue (410.4 ml) than in controls
      (275.5 ml, p = 0.016). No difference was noted between the two groups for the
      volume of drainage fluid of the site of mastectomy or lumpectomy, or for the
      total volume of drainage fluid. Drainage duration as well as duration of hospital
      stay were similar. Six complications occurred in group A, and one in group B (p =
      0.037).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589008
TI  - Role of humoral immune responses in hepatitis B and C virus infections.

PMID- 7589006
TI  - The effect of intraoperative mebendazole-albendazole applications on the
      hepatobiliary system.
AB  - Caustic sclerosing cholangitis occurs with the use of scolicidal solutions in
      liver hydatid disease draining into the biliary system. In this study, we
      investigated the effectiveness of benzimidazole solutions, their in vitro
      scolicidal effects and the histopathological changes in the hepatobiliary system
      due to their intraoperative use. It was found that 5 mg% mebendazole and 1 mg%
      albendazole have strong scolicidal effects. In an in vivo study, under general
      anesthesia, 5% mebendazole in group I, 1% albendazole in group II and normal
      saline in group III were injected into the biliary system of rabbits. Liver
      biochemical tests showed no significant changes. More elaborate ductal mucosal
      proliferation, ductal dilatation and periductal fibrosis were found in group I
      compared with group II in biopsies taken on the 60th day. The biopsies of group
      III were normal.

PMID- 7589011
TI  - Simvastatin decreases the hepatic secretion of very-low-density lipoprotein
      apolipoprotein B-100 in heterozygous familial hypercholesterolaemia:
      pathophysiological and therapeutic implications.
AB  - We studied six patients with heterozygous familial hypercholesterolaemia (FH)
      before and after 8 weeks of treatment with simvastatin (40 mg day-1), an
      inhibitor of 3-hydroxy-3-methyl-glutaryl-Coenzyme A. Simvastatin decreased plasma
      low-density lipoprotein (LDL) cholesterol by 43% (P = 0.002), triglycerides by
      15% [corrected] (P = 0.05) and mevalonic acid (a measure of in vivo cholesterol
      synthesis) by 20% (P = 0.002); high-density lipoprotein cholesterol increased by
      17% (P = 0.02). The hepatic secretion rate of very-low-density lipoprotein
      apolipoprotein B-100 (VLDL apoB) was measured directly using a primed, constant
      intravenous infusion of 1-[13C]-leucine with monitoring of the isotopic
      enrichment of apoB by gas chromatography-mass spectrometry; fractional secretion
      rate (FSR) was derived using a monoexponential function. Simvastatin decreased
      the FSR, ASR and pool size of VLDL apoB by 17% (14.3 (SEM 3.6)) vs. (11.9 (SEM
      3.5) pools day-1, P = 0.10), 83% (51.4 (SEM 17.9) vs. (8.6 (SEM 1.4), P = 0.007
      mg kg-1 day-1) and 65% (234.2 (SEM 30.4) vs. 82.6 (SEM 24.0) mg, P = 0.02),
      respectively. The change in the ASR of VLDL apoB was significantly correlated
      with the change in plasma LDL cholesterol concentration (P = 0.04), but not with
      the change of triglyceride or mevalonic acid. We conclude that the hepatic
      secretion of VLDL apoB in FH is decreased by simvastatin, which may partly
      explain the fall in plasma cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589009
TI  - Prolonged activation of the branched-chain alpha-keto acid dehydrogenase complex
      in muscle of zymosan treated rats.
AB  - Whole-body oxidation rates of branched chain amino acids (BCAA) are increased
      during catabolic diseases. A significant role for muscle in this feature has been
      suggested and, therefore, activities of the rate limiting enzyme in the
      degradative pathway of the BCAA in muscle were investigated in a catabolic rat
      model (intraperitoneal zymosan injection). Both actual and total activities of
      the branched chain alpha-keto acid dehydrogenase complex zymosan treated rats and
      compared with values measured in pair fed and ad libitum fed controls. The actual
      activity and the percentage of the enzyme in the active form were increased 2 and
      6 days after the zymosan challenge. Total activity of the BC-complex and the
      activities of mitochondrial marker enzymes were reduced 2 days after zymosan
      treatment. We conclude that zymosan treatment leads to (1) a reduction of the
      mitochondrial content in skeletal muscle and (2) a prolonged activation of the BC
      complex in muscle which may explain enhanced oxidation of BCAA during catabolic
      diseases.

PMID- 7589005
TI  - Renal functional alterations in extrahepatic cholestasis: can oxidative stress be
      involved?
AB  - Renal function may be compromised by extrahepatic cholestasis. In this context,
      the nephrotoxic role of bile salts is well known. Recently, however, it has been
      claimed that other factors, such as lipid peroxides, are involved. We therefore
      created bile duct ligation in 40 Sprague-Dawley rats. During the follow-up (from
      1 to 28 days), significant variations were found in liver histological
      parameters, but not in renal morphology. Fourteen days after ligation,
      significant increases were found in serum and urinary thiobarbituric-acid
      reactive species and phospholipase A2 (indirect indices of lipid peroxidation),
      whereas 8-10 days after ligation, a significant decrease was observed in
      erythrocytic and hepatic GSH levels. The variations in urinary thiobarbituric
      acid-reactive species and in phospholipase A2 were not correlated with
      concomitant variations in the sera. Urinary lipid peroxides were directly
      correlated with the degree of liver morphological alterations and inversely with
      circulating GSH. Urinary outputs of lipid peroxides, phospholipase A2 and N
      acetyl-glucosaminidase were correlated with each other. These results suggest
      that there is an imbalance in the oxidative-antioxidant hepatic system in
      experimental extrahepatic cholestasis. The reduced bioavailability of blood GSH
      may alter the oxidative equilibrium in other organs, such as the kidney,
      triggering and favoring the lipoperoxidative cascade.

PMID- 7589012
TI  - Influence of residual C-peptide secretion on the arginine vasopressin response to
      hypoglycaemia and metoclopramide in insulin-dependent diabetes.
AB  - Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to
      insulin-induced hypoglycaemia has been described in type I diabetes mellitus. In
      the present study, we examined whether residual endogenous insulin secretion may
      play a role in the control of this abnormal AVP secretory pattern. For this
      purpose, 21 insulin-dependent diabetic men and 10 age- and weight-matched normal
      men were tested with MCP (20 mg in an i.v. bolus). On a different occasion,
      subjects were tested with insulin (0.15 IU kg-1). The diabetic patients were
      subdivided into C-peptide negative patients (CpN, 11 patients without detectable
      endogenous pancreatic beta cell activity) (group I) and C-peptide positive
      patients (CpP, 10 patients with residual endogenous insulin secretion) (group
      II). Experiments started after optimization of the metabolic status of the
      diabetic men by 3 days of treatment with continuous subcutaneous insulin
      infusion. The basal concentrations of AVP were similar in all groups. The
      administration of MCP induced a striking elevation in plasma AVP levels in the
      normal controls and in the diabetic subjects of groups I and II. However, the AVP
      rise was significantly higher in group I and group II than in normal controls.
      Furthermore, group I diabetics showed higher AVP increments than group II.
      Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even
      though the diabetic subjects of groups I and II had a delayed recovery in blood
      glucose levels. The hypoglycaemic pattern was similar in group I and II.
      Hypoglycaemia induced a striking AVP increase in the normal controls.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7589010
TI  - Body composition and serum lipids in female runners: influence of exercise level
      and menstrual bleeding pattern.
AB  - The impact of running and menstrual disturbances on regional and total body fat
      distribution and serum lipids was investigated in 205 women. Body composition was
      measured by dual-energy X-ray absorptiometry. The total fat mass in the elite
      runners was approximately half of the normally active's (7.3 [0.48] kg vs. 14.3
      [0.49] kg, P < 0.001) (mean [SEM]). The difference was most pronounced in the
      abdomen (fat percentage 9.7 [0.85]% vs. 22.0 [0.88]%, P < 0.001). The elite
      runners tended to have a more favourable lipid profile than the normally active
      (NS). A significant relation was found between lipoproteins and body fatness. In
      comparison with the regularly menstruating runners (n = 93), the 13 runners with
      amenorrhea tended to have less body fat and slightly less favourable lipid
      profiles (NS). In conclusion, regular exercise was associated with a low
      abdominal fat percentage, which may affect cardiovascular risk beneficially.
      Running-associated menstrual dysfunctions were not significantly related to a
      specific body composition or serum lipid profile.

PMID- 7589013
TI  - Hyperlipidaemia in renal transplantation--risk factor for long-term graft
      outcome.
AB  - The role of hyperlipidaemia for the outcome of renal transplantation was
      evaluated in a prospective study involving 151 patients. Graft losses were
      associated with more pronounced pre-transplant lipid abnormalities. An increased
      risk of graft loss during the first two post-transplant years was found in
      patients with marked pre-transplant hypercholesterolaemia (> or = 6.9 mmol L-1, P
      = 0.014; relative risk 2.2). Hypercholesterolaemia > or = 6.9 mmol L-1 at 6
      months after transplantation, present in 41/115 patients, was associated with a
      lower GFR (P = 0.007) and more pronounced albuminuria (P = 0.009) at 2 years. In
      patients with graft dysfunction (serum creatinine > 160 mumol L-1) at 2 years,
      more pronounced lipid abnormalities before and at 6 months after transplantation
      were found. Between 6 months and 2 years, total and LDL cholesterol did not
      change significantly, but HDL cholesterol decreased (P = 0.03). In conclusion,
      hyperlipidaemia is also a risk factor for the long-term outcome in renal
      transplantation. Further investigations are needed to determine whether graft
      losses and late graft failure can be prevented or ameliorated by treating
      hyperlipidaemia in renal transplantation.

PMID- 7589014
TI  - Microdialysis assessment of adipose tissue metabolism in post-absorptive obese
      NIDDM subjects.
AB  - Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the
      influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis
      combined with 133Xe clearance and measurements in arterialized plasma were
      carried out using samples of subcutaneous abdominal fat from nine obese NIDDM
      subjects (glucose, 7.9 +/- 0.7 mmol L-1) (mean +/- SEM) and nine obese non
      diabetic subjects (glucose, 4.9 +/- 0.1) matched for age, BMI and body fat. After
      an overnight fast arterialized plasma levels were 1145 +/- 110 vs. 876 +/- 59
      mumol L-1 (P < 0.05) for lactate and 75 +/- 10 vs. 66 +/- 8 mumol L-1 for
      glycerol in the diabetic and control group, respectively. The corresponding
      abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278
      +/- 63 vs 1107 +/- 64 mumol L-1 and 314 +/- 28 vs. 311 +/- 17 mumol L-1,
      respectively. However, adipose tissue blood flow in the same region was lower in
      NIDDM subjects (1.5 +/- 0.2 vs 2.4 +/- 0.3 mL 100 g-1 min-1) (P < 0.05).
      Consequently, apparent subcutaneous lactate and glycerol release, estimated
      according to Fick, were not statistically different in the two groups (1.8 +/-
      0.4 vs 2.4 +/- 0.8 and 2.1 +/- 0.4 vs 3.1 +/- 0.5 mumol kg-1 min-1 in NIDDM and
      control subjects, respectively). Thus, in the post-absorptive state apparent
      lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM
      subjects was similar to that in a matched group of obese non-diabetic
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589015
TI  - Elevation of D-glucose impairs coronary artery autoregulation after slight
      reduction of coronary flow.
AB  - Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic
      injury through D-glucose-induced alterations of intracellular metabolism.
      Therefore the effects of hyperglycaemia on coronary artery autoregulation under
      slight reduction of coronary flow were investigated in isolated perfused guinea
      pig hearts. Under normal (10 mM) D-glucose concentrations coronary autoregulation
      was intact in response to a slight reduction of coronary flow (from 6 to 4.5 mL
      min-1) when L-arginine as a precursor of the endothelium-derived relaxing factor
      (EDRF/NO) was available and formation of prostaglandines was intact. Under high
      (44 mM) D-glucose concentrations on the other hand, a sustained vasodilatation
      dependent on the availability of L-arginine was observed, when formation of
      prostaglandins was blocked. This effect was partially reduced in the presence of
      prostaglandin synthesis. Furthermore, the effect of L-arginine under both
      conditions could be antagonized by the L-arginine-analogue NG-nitro-L-arginine
      methyl-ester (100 microM). Our results suggest that hyperglycaemia impairs
      coronary artery autoregulation by reducing the threshold for hypoxic
      vasodilatation in an EDRF/NO-dependent manner. Concomitantly a shift from the
      formation of vasodilatatory to vasoconstrictive prostaglandines was observed.
      These results might be of particular interest in patients with diabetes mellitus
      and ischaemic heart disease.

PMID- 7589017
TI  - Key metabolite kinetics in human skeletal muscle during ischaemia and
      reperfusion: measurement by microdialysis.
AB  - The tissue kinetics of key metabolites of ischaemic and postischaemic tissue
      damage were studied in the intercellular space of human skeletal muscle by
      microdialysis. In vivo microdialysis calibration experiments (n = 5) yielded the
      basal intercellular concentration of glucose in human skeletal muscle (3.6 +/-
      0.6 mM; mean +/- SD). The corresponding mean plasma glucose concentration was 4.3
      +/- 0.2 mM which was significantly higher. The time vs. concentration profiles of
      intercellular glucose (n = 7), lactate (n = 5), TxB2 (n = 6) and urea (n = 8)
      were characterized during a 20 min period of leg constriction. TxB2 increased
      exclusively during reperfusion in comparison to baseline (n = 6). Administration
      of 500 mg acetylsalicylic acid, 5-10 min after onset of ischaemia blunted TxB2
      response to reperfusion (n = 4). It is concluded that intercellular muscle
      glucose concentration is less than that in plasma. Glucose uptake in skeletal
      muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is
      not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced
      by acetylsalicylic acid, even if administered after onset of ischaemia.

PMID- 7589016
TI  - Four week administration of an ACE inhibitor and a cardioselective beta-blocker
      in healthy volunteers: no influence on insulin sensitivity.
AB  - In most, but not all, studies antihypertensive treatment with angiotensin
      converting enzyme inhibitors (ACE inhibitors) improves insulin sensitivity,
      whereas beta-blockers decrease insulin sensitivity. However, there was a
      significant increase in body weight with beta-blockers and changes in the body
      potassium homeostasis with ACE inhibitors. In order to compare the drug specific
      metabolic effects of an ACE inhibitor and a cardioselective beta-blocker
      controlling these factors, we measured insulin sensitivity in a randomized,
      double-blind cross-over study in 22 healthy volunteers (age 27 +/- 3 years; BMI
      22.0 +/- 1.5 kg m-2 (mean +/- SD)) during euglycaemic glucose clamps before and
      after 4 weeks' administration of 5 mg Lisinopril or 5 mg Bisoprolol. Both drug
      phases were separated by 4 weeks of no drug administration. During the insulin
      sensitivity measurements potassium concentrations were clamped at basal levels by
      means of a variable i.v. potassium infusion. Body weight was monitored at weekly
      intervals and kept constant within +/- 1 kg of the subjects' baseline weight
      throughout the entire study period. Insulin sensitivity did not change
      significantly during either drug administration period. The insulin sensitivity
      index of the 22 volunteers after administration of the ACE inhibitor was 7.9 +/-
      2.4 mL min-1 m2 microU-1 mL-1 (basal index 8.3 +/- 1.9 mL min-1 m2 microU-1 mL-1,
      and 7.5 +/- 2.1 mL min-1 m2 microU-1 mL-1 after administration of the beta
      blocker (basal index 8.2 +/- 1.9 mL min-1 m2 microU-1 mL-1; NS).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589018
TI  - Reduced glomerular size- and charge-selectivity in clinically healthy individuals
      with microalbuminuria.
AB  - The pathophysiologic mechanism behind microalbuminuria, a potential
      atherosclerotic risk factor, was explored by measuring fractional clearances of
      four endogenous plasma proteins of different size and electric charge (albumin,
      beta 2-microglobulin, immunoglobulin G, and immunoglobulin G4). Twenty-eight
      clinically healthy individuals with microalbuminuria, defined as a urinary
      albumin excretion of 6.6-150 micrograms min-1, and 60 matched control subjects
      were studied. Fractional immunoglobulin G clearance was higher (geometric means
      (95% confidence intervals)) 3.0 (2.3-3.9) x 10(-6), n = 28, vs. 2.1 (1.8-2.4) x
      10(-6), n = 60; P = 0.02), whereas the ratio immunoglobulin G
      clearance/immunoglobulin G4 clearance was lower (geometric means (95% confidence
      intervals)) 1.8 (1.4-2.2), n = 28, vs. 2.3 (2.0-2.5), n = 60; P = 0.03) in
      microalbuminuric than in normoalbuminuric individuals. Fractional beta 2
      microglobulin clearance was similar in the two groups. Since total IgG and the
      IgG4 subclass are of similar size and configuration but electrically neutral and
      negative, respectively; these findings indicate that microalbuminuria is
      associated with decreased size- and charge-selectivity of the glomerular vessel
      wall. Hypothetically, such alterations may reflect generalized vascular
      abnormalities linking microalbuminuria to atherogenesis.

PMID- 7589019
TI  - Treatment of systemic mastocytosis with interferon-gamma: failure after
      appearance of anti-IFN-gamma antibodies.
AB  - We report a case of a patient with systemic mastocytosis who was treated with
      interferon-gamma. Because of severe diarrhoea, nausea and weight loss due to mast
      cell infiltration of the gastric mucosa the patient received 150 micrograms d-1
      interferon-gamma subcutaneously for 10 months. During therapy, the plasma
      concentrations of IL-3, IL-4 and GM-CSF, which seem to play a role in mast cell
      growth and differentiation were monitored. The patient had good symptomatic
      relief and the initially very high eosinophil counts in the peripheral blood
      showed a partial reduction. However, after 4 months of therapy the patient
      relapsed. In serum obtained after the relapse, but not in stored serum from the
      beginning of the therapy, neutralizing antibodies against interferon-gamma were
      found. Therefore an initial response to the therapy and a secondary failure
      mediated by treatment-induced antibodies against recombinant interferon-gamma
      might be suggested. Interferon-gamma may be a well tolerated therapeutic option
      in systemic mastocytosis. However, treatment-induced neutralizing antibodies
      against recombinant interferon-gamma should be considered if secondary treatment
      failure occurs.

PMID- 7589021
TI  - LTC4 in normal urine.

PMID- 7589020
TI  - The effect of starvation on leucine, alanine and glucose metabolism in obese
      subjects.
AB  - The relationship between changes in ketone concentrations and leucine metabolism
      (seven obese subjects), glucose and alanine metabolism (seven obese subjects) was
      investigated using radioisotopic techniques after 12 h, 60 h and 2 weeks
      starvation. Leucine metabolism was also measured in five lean subjects after 12 h
      and 60 h starvation. In the obese subjects leucine concentration increased after
      60 h starvation and leucine metabolic clearance rate, glucose and alanine
      concentration decreased (P < 0.05). Glucose and alanine production rate (Ra)
      decreased after 2 weeks (P < 0.05) but there was no change in leucine Ra after 60
      h or 2 weeks. In the lean subjects leucine concentration, production rate and
      oxidation rate were increased after 60 h (P < 0.005, P < 0.05, P < 0.05). Ketone
      concentration was inversely related to alanine Ra (r = -0.51, P < 0.02) but was
      not related to measurements of protein metabolism in the obese subjects. This
      study demonstrates that the effect of short-term starvation on protein metabolism
      differs in lean and obese subjects. The decrease in glucose Ra during long-term
      starvation may be in part due to a decreased supply of alanine for
      gluconeogenesis.

PMID- 7589022
TI  - Comparison of the onset and duration of the analgesic effect of dipyrone, 1 or 2
      g, by the intramuscular or intravenous route, in acute renal colic.
AB  - In a double-blind, double-dummy randomized controlled clinical trial, the onset
      and duration of the analgesic effect of dipyrone, 1 or 2 g, and diclofenac
      sodium, 75 mg, by either the i.m. or the i.v. route were compared in 293 patients
      (aged 18-70 years) with acute renal colic. A level of > or = 50 mm on the 100-mm
      visual analogue scale was required for inclusion in the study. Patients were
      randomly allocated to six treatment groups, receiving dipyrone 1 g i.m., dipyrone
      1 g i.v., dipyrone 2 g i.m.;, dipyrone 2 g i.v., diclofenac sodium 75 mg i.m.;
      and diclofenac sodium 75 mg i.v., respectively. Evaluations were performed at 10,
      20, 30, and 60 min and 2, 4, and 6 h after treatment (time 0). Primary efficacy
      end points included course of pain, total pain, percentage of patients with a
      pain improvement of 50% or more at each evaluation time, pain intensity evaluated
      by the investigator on a 0-3 scale, and differences in pain intensity. The
      analgesic response was more marked and prolonged among patients receiving
      dipyrone 2 g i.m. or dipyrone 2 g i.v. There were no significant differences
      between dipyrone 1 g and diclofenac sodium 75 mg, by either the i.m. or the i.v.
      route. All treatment regimens were well tolerated.

PMID- 7589023
TI  - Haemodynamic evaluation of two regimens of molsidomine in patients with chronic
      congestive heart failure.
AB  - We investigated the extent and duration of the haemodynamic effects of two
      regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4
      mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily
      in 13 patients with chronic congestive heart failure using a placebo-controlled,
      randomized, double-blind and crossover protocol over a period of 12 h. Both
      regimens significantly affected systolic, mean and diastolic pulmonary arterial
      pressure (reductions of up to 15%), right atrial pressure (reductions of up to
      35%) and total pulmonary resistance (reductions of up to 18%). The lower dose
      achieved its maximum action after about 1 h and remained effective for 2 h,
      whereas the higher dose in sustained-release form showed maximal efficacy at 2 h
      and remained active even at 12 h. In contrast, only minor changes in arterial
      blood pressure, systemic vascular resistance and cardiac output were observed on
      both regimens, almost exclusively at 2 h. Heart rate was not affected by either
      of the regimens tested. Neither regimen led to any untoward adverse effects.
      Thus, molsidomine is a potent vasodilating agent which, apart from its effects on
      preload, also acts on pulmonary arterial and right atrial pressures, leaving
      systemic circulation largely unaffected on the regimens tested. Administered on
      its own, it is therefore suitable for treatment of congestive heart failure.

PMID- 7589025
TI  - Randomised crossover comparison of adrenal suppressive effects of dermal creams
      containing glucocorticosteroids.
AB  - To compare the effect of multiple dose treatment with fatty cream 0.1%
      hydrocortisone-17-butyrate (LLFC) and fatty cream 0.1% mometasone furoate (EFC),
      under occlusion on adrenal function, we performed an open label, randomised, two
      period crossover study, lasting 30 days, in 12 healthy, male volunteers (age 18
      45 y). Morning plasma cortisol and ACTH concentrations were determined before,
      during, and after the treatments, and a Synacthen test was performed before and
      during the treatments. Both agents suppressed plasma cortisol concentrations, EFC
      significantly more than LLFC. ACTH concentrations were normal and were comparable
      between the two treatments throughout the studies, while the Synacthen tests
      showed normal rises in cortisol levels. Both treatments were well tolerated. We
      conclude that EFC has a stronger suppressive effect on plasma cortisol values
      than LLFC, although for short duration treatments both suppressive effects are
      transient.

PMID- 7589024
TI  - Effects of daytime administration of zolpidem versus triazolam on memory.
AB  - To determine whether zolpidem (an imidazopyridine hypnotic) produces amnestic
      effects which are similar to those produced by triazolam (a benzodiazepine
      hypnotic), 70 subjects were administered either triazolam (0.125, 0.25, or 0.5
      mg), zolpidem (5, 10, or 15 mg) or placebo, then tested on Simulated Escape,
      Restricted Reminding, and Paired-Associates memory tests at 1.5 hours post-dosing
      (i.e., near the time of estimated peak blood concentration for both drugs) and
      again at 6 hours post-dosing. Triazolam 0.5 mg produced the greatest memory
      impairment at both test times, and also produced the greatest degree of sedation
      during intervening daytime naps in a non-sleep-conducive environment. Other doses
      of triazolam and zolpidem produced less memory impairment, but also failed to
      significantly enhance sleep. The results are consistent with the view that the
      amnestic and hypnotic effects of these sleep-inducing medications are
      functionally coupled.

PMID- 7589026
TI  - Functional capacity in healthy volunteers before and following beta-blockade with
      controlled-release metoprolol.
AB  - The effects of the beta 1-selective beta-adrenergic blocker metoprolol on
      physiological responses, exercise capacity and gas exchange parameters were
      measured in healthy men using different graded bicycle exercise protocols on
      separate days before and following administration of 200 mg controlled-release
      metoprolol. Eleven men performed in randomised order maximal cardiopulmonary
      exercise testing on 50-W/6-min stage, 50-W/3-min stage and ramp (15-W/min-1)
      protocols. Peak heart rate and peak heart rate-blood pressure products were
      similar on all exercise protocols, and were significantly reduced by metoprolol.
      Submaximal and peak oxygen consumption were similar before and following beta
      adrenoceptor blockade. Depending on the exercise protocol applied, an
      insignificant decrease of 4-10% in maximal cumulated exercise capacity (work-rate
      x time integral) was observed following administration of metoprolol. It is
      concluded that in healthy men evaluated with different exercise protocols the
      beta 1-selective controlled-release beta-adrenoceptor blocker metoprolol does not
      influence exercise capacity despite a marked reduction of heart rate and rate
      pressure product.

PMID- 7589027
TI  - Effects of a Finnish sauna on the pharmacokinetics and haemodynamic actions of
      propranolol and captopril in healthy volunteers.
AB  - The effects of a Finnish sauna on propranolol pharmacokinetics and on the
      pharmacodynamics of propranolol and captopril were studied in healthy, young
      volunteers (2 males, 6 females) in a double-blind, cross-over trial. The subjects
      received single oral doses of placebo, propranolol (40 mg) or captopril (12.5 mg)
      in sauna and control sessions at a one-week interval. The sauna sessions
      consisted of three repetitive 10-min stays in a sauna (85-100 degrees C, relative
      humidity 25-35%) separated by two 5-min rest periods in a cool room. Sauna
      bathing started 35, 50 and 65 min after ingestion of the drugs. Venous blood for
      plasma propranolol measurement were collected before and 15, 30, 45, 60, 75, 90
      min and 2, 3, 4, 5, 7 and 24 h after drug intake. The sauna significantly
      increased the maximum concentration (Cmax 41 vs. 28 ng.ml-1) of propranolol and
      the mean plasma propranolol concentration 60 and 90 min, and 2 and 3 h after drug
      administration. It also significantly increased the AUC0-5h (119 vs 71
      micrograms.h.l-1) of propranolol from 0 to 5 hours tmax, t1/2 beta and AUC0-24h
      of propranolol did not differ between the control and sauna sessions. The higher
      propranolol levels during and after the cessation of sauna bathing did not lead
      to significant changes in blood pressure or heart rate compared to the control
      period. Captopril had no major effects on these parameters during the post-sauna
      phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589028
TI  - Venous plasma levels of endothelin-1 are not altered immediately after
      nitroglycerin infusion in healthy subjects.
AB  - Endothelin-1 and nitric oxide play an important regulatory role in the control of
      vascular smooth muscle tone. Nitroglycerin (NTG), a nitric oxide donating drug,
      may inhibit endothelin production. In this double-blind placebo-controlled
      crossover study, plasma levels of endothelin-1 were measured before and
      immediately (5-30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline
      in 12 healthy subjects. On two different days separated by at least 1 week, NTG
      in four different doses, 0.015, 0.25, 1.0, and 2.0 micrograms. kg-1. min-1, or
      placebo (isotonic saline) was infused successively for 20 min each dose. During
      the infusion blood pressure and heart rate were measured. NTG infusion
      significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and
      pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1
      beats. min-1. No changes in endothelin-1 plasma levels were induced by NTG
      infusion (2.4 pg.ml-1 before NTG vs. 2.7 pg.ml-1 after NTG) and placebo infusion
      also did not affect plasma endothelin-1. It is concluded that venous plasma
      levels of endothelin-1 are not altered immediately after NTG infusion.

PMID- 7589032
TI  - Influence of ethinylestradiol-containing combination oral contraceptives with
      gestodene or levonorgestrel on caffeine elimination.
AB  - In a controlled clinical trial, the elimination of caffeine was examined in 20
      healthy women prior to and during one cycle of treatment with either of two oral
      contraceptive formulations, one containing 0.075 mg gestodene and 0.03 mg
      ethinylestradiol and one containing 0.125 mg levonorgestrel and 0.03 mg
      ethinylestradiol. In addition, caffeine clearance was determined 1 month after
      the last intake of the oral contraceptives. Compared with pretreatment values,
      the clearance of caffeine was reduced by about 54% and 55% after one treatment
      cycle with gestodene- and the levonorgestrel-containing oral contraceptive,
      respectively. Other pharmacokinetic parameters of caffeine, such as tmax and
      Cmax, were not affected. Clearance values returned to pretreatment values 1 month
      after the last administration of the oral contraceptives. There was no difference
      in the reduction of caffeine clearance between contraceptive formulations. A
      small, but significant difference in the AUC(0-24 h) values of ethinylestradiol
      was noted between both preparations. There was no correlation between the
      AUC(model) values of caffeine and the AUC(0-24 h) values of ethinylestradiol. In
      the present study, a somewhat more pronounced effect on the elimination of
      caffeine was observed than in previous investigations, where several
      contraceptive steroids were administered only for a period of 2 weeks.

PMID- 7589030
TI  - Pharmacokinetic interactions of alcohol and acetylsalicylic acid.
AB  - This study assessed the influence of acetylsalicylic acid (ASA, 1.0 g), ibuprofen
      (0.8 g) and paracetamol (1.0 g) on the single-dose kinetics of ethanol in 12
      healthy volunteers ingesting the drug and a standardised 1840-kJ breakfast 1 h
      before intake of ethanol. It also assessed the influence of ethanol on the single
      dose kinetics of 1.0 g ASA in ten fasting healthy volunteers. Plasma
      concentrations of ethanol were measured by gas chromatography, and those of the
      drugs by liquid chromatography. There was no effect of ASA, ibuprofen or
      paracetamol on the single-dose kinetics of ethanol, but concurrent intake of
      ethanol reduced the peak concentration of ASA by 25%.

PMID- 7589033
TI  - Effects of altitude (4300 m) on the pharmacokinetics of caffeine and cardio-green
      in humans.
AB  - The effects of chronic exposure to high altitude on the pharmacokinetics of
      caffeine and cardio-green (ICG) were examined in eight healthy males (23-35 y) at
      sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg. kg
      1) was administered as an intravenous bolus and caffeine (4 mg. kg-1) in an
      orally ingested solution. The concentration of ICG, caffeine, and the primary
      metabolites of caffeine (MET) were determined in serial blood samples and their
      pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant
      decrease in a caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve
      (2.5 vs 3.7 g.l-1.min-1), and increased clearance (117 vs 86 ml.min-1.70 kg-1).
      In ALT the area under the curve the ICG significantly decreased (85 vs 207 mg.l
      1.min-1) and the volume of distribution and clearance increased (5.2 vs 2.4 l and
      532 vs 234 ml.min-1 respectively) compared to SEA. There was a significant
      increase in the AUC ratio of MET to caffeine indicating that either metabolite
      formation or elimination was increased in ALT. These results demonstrate that in
      humans, chronic exposure to 4300 m results in the modification of the
      pharmacokinetics of caffeine and ICG.

PMID- 7589031
TI  - Population pharmacokinetics of zileution, a selective 5-lipoxygenase inhibitor,
      in patients with rheumatoid arthritis.
AB  - The pharmacokinetics of zileuton, a novel selective 5-lipoxygenase inhibitor,
      were studied in 37 patients with rheumatoid arthritis after administration of 200
      mg, 400 mg, and 600 mg, zileuton for 4 weeks. Patients had 6-h pharmacokinetic
      evaluation of zileuton on day 14. Plasma zileuton concentrations were quantitated
      using HPLC. Zileuton pharmacokinetic parameters were estimated using standard
      noncompartmental methods. A population analysis of zileuton pharmacokinetics was
      also performed with the NONMEM computer program. The pharmacokinetics of zileuton
      in patients with rheumatoid arthritis were similar to those previously estimated
      in normal healthy humans. The peak concentrations and the areas under the curves
      during the dosing interval were dose proportional. The noncompartmental means of
      the CL/f, terminal-phase half-life, and V/f of zileuton were approximately 545 ml
      min-1, 1.4 h, and 64.3 1, respectively. The estimate of population typical values
      of the CL/f for a 70-kg person (540 ml min-1) and V/f for a 70-kg person (64.8 1)
      from the NONMEM analysis were in agreement with the noncompartmental estimates.
      Differences in body weight, but not age or gender, helped explain some of the
      variability in the pharmacokinetics of zileuton in patients. Therefore, there is
      no pharmacokinetic basis for alteration of the zileuton dose size or the dosing
      schedule in patients with rheumatoid arthritis.

PMID- 7589034
TI  - The healthy volunteer in clinical pharmacology: personality and motivation.
AB  - The aim of the present study was to quantify the personality structure and
      motivation of medical students, who are often the most readily available source
      of healthy volunteers, since it has long been known that the pharmacodynamics and
      pharmacokinetics of drugs can be substantially modified by predominant
      personality traits (e.g. neuroticism, extraversion). Over the course of 4 years,
      a total of 337 subjects (165 males, 172 females) out of the 496 medical students
      asked, participated in the study after appropriate instruction. Students were
      tested using the Motivation Q-Sort method which, by means of questions
      ("questionnaire sort"), investigates whether a subject tends to react in a
      success-motivated (SM) or a failure-motivated (FM) mode. The variable measured is
      the so-called net hope (NH), where NH > 1.6 corresponds to SM and NH < -0.3
      corresponds to FM. We also used the Freiburg Personality Inventory (FPI) as a
      suitable method of determining personality structure. The predominant traits of
      interest found were nervousness (FPI 1), extraversion (FPI E), and neuroticism
      (FPI N). In the first series of tests (primary selection), motivation only was
      determined in 337 volunteers. The range was fairly broad, with NH values from
      4.32 (highly SM) to -3.09 (highly FM). In the second series of tests, about 60 SM
      and 60 FM subjects were selected. The Motivation Q-Sort method was repeated with
      students placed under more difficult conditions, and the FPI was also
      performed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589029
TI  - Lack of interaction between two antihistamines, mizolastine and cetirizine, and
      ethanol in psychomotor and driving performance in healthy subjects.
AB  - The pharmacodynamic interaction between mizolastine, a new H1 antihistamine, and
      ethanol was assessed in a randomized, double-blind, three-way crossover, placebo
      controlled study. Eighteen healthy young male volunteers received mizolastine 10
      mg, or cetirizine 10 mg or placebo once daily for 7 days with a 1-week wash-out
      interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on
      days 5 or 7 of each treatment period, was administered to achieve a peak blood
      alcohol concentration (BAC) of 0.7 g/l then maintained for 1 h by two further
      doses of ethanol. Driving ability and psychomotor performance were evaluated
      using actual and simulated driving tests, critical flicker fusion threshold
      (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a
      significant decrement in all tasks up to 5.5 h after administration: an increase
      in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction
      time of 80 ms, in driving test and DAT performance of + 3.2; and a decrease in
      CFF and in tracking speed of 2.6 m.s-1. Neither mizolastine nor cetirizine
      significantly impaired driving ability or arousal (CFF) compared with the
      placebo. However, both drugs significantly impaired DAT performance 6:00 h post
      dose (increase of + 2.1 for mizolastine and + 2.4 for cetirizine). The tracking
      speed was significantly decreased 7:50 h after mizolastine administration (-1.3
      m.s-1) and more consistently from 1:30 to 7:50 h after cetirizine administration
      (-1.4 m.s-1). No significant adverse interaction, i.e. potentiation, occurred
      between ethanol and either antihistamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589036
TI  - The International Conference on Harmonisation.

PMID- 7589037
TI  - Classification of drugs for teratogenic risk.

PMID- 7589035
TI  - Effect of a synthetic prostaglandin E2 analogue, RS-86505-007, on plasma lipids
      and lipoproteins in patients with moderate hypercholesterolaemia: efficacy and
      tolerance of treatment and response in different apolipoprotein polymorphism
      groups.
AB  - A double-blind, placebo-controlled ascending dose trial was carried out to
      evaluate the hypocholesterolaemic efficacy and tolerance of RS-86505-007, a
      prostaglandin E2 analogue, in moderately hypercholesterolaemic patients. Twenty
      four patients received an oral dose of RS-86505-007 3 micrograms t.i.d. and a
      separate group of 26 patients 6 micrograms t.i.d. for 6 weeks. Plasma total and
      low-density lipoprotein (LDL) cholesterol concentrations decreased after 2 weeks
      of treatment, and the reductions were dose dependent. After 6 weeks of treatment
      (6 micrograms t.i.d.), the reductions from baseline in total and LDL cholesterol
      concentration were 14.6% and 18.5%, respectively. No changes in the plasma
      concentration of triglycerides or high-density lipoprotein (HDL) cholesterol were
      observed. RS-86505-007 tended to reduce total and LDL cholesterol concentrations
      less in patients with the epsilon 4 allele of the apolipoprotein E than in those
      with epsilon 3 allele. In contrast, the XbaI or EcoRI polymorphisms of the
      apolipoprotein B gene seemed to have no effect on the hypocholesterolaemic
      efficacy of the drug. The drug had no effect on the lipoprotein (a)
      concentration. Sixty-three percent of patients receiving 3 micrograms t.i.d. and
      81% receiving 6 micrograms t.i.d. had adverse events, two-thirds of which related
      to the gastrointestinal tract. One patient in the 3-micrograms group and three
      patients in the 6-micrograms group terminated the study prematurely due to
      adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589039
TI  - Recovery characteristics following anaesthesia with sevoflurane or propofol in
      adults undergoing out-patient surgery.
AB  - The aim of the study was to compare recovery characteristics in adult patients
      following general anaesthesia either with the new investigational volatile agent
      sevoflurane or with propofol. Accordingly, two groups of 25 adults undergoing
      outpatient surgery were entered into a prospective, randomised study. Patients
      who received sevoflurane were extubated at an earlier stage than those receiving
      propofol (6.6 vs. 9.8 min), and the times to eye opening (7.2 vs. 12.6 min) and
      hand squeezing (8.2 vs 13.8 min) were also shorter. As measured by the digit
      symbol substitution test, patients regained the pre-operative level of cognitive
      function significantly earlier after sevoflurane anaesthesia. Modified Aldrete
      scores were also higher in this group within the first hour after anaesthesia
      than in the propofol group. Sevoflurane appears to be a useful alternative to
      propofol in outpatient anaesthesia.

PMID- 7589038
TI  - Sample sizes for comparative inhaled corticosteroid trials with emphasis on
      showing therapeutic equivalence.
AB  - In the near future it is to be expected that many new inhaled corticosteroids or
      formulations of these drugs will be compared with older ones, to discover whether
      they are therapeutically equivalent or not. The statistical evaluation of these
      trials differs from the classic methods. When two averages are similar or differ
      only slightly, power is very low. The regulatory bodies demand a power of at
      least 80%. This problem was initially solved by using the so-called power
      approach. Researchers included enough volunteers to enable them to detect a
      predefined difference, considered to be without any clinical significance, with a
      power of 80%. This approach, however, has been shown to be incorrect and has been
      replaced by the two one-sided tests procedure, where a new sample size equation
      is derived. Important elements of this new equation are the coefficient of
      variation of the parameter measured, the difference between the averages of the
      two groups and the equivalence limit (the difference between the means still
      tolerable). This equation was used in the present study to estimate the number of
      volunteers needed in a parallel inhaled corticosteroids equivalence trial. The
      end points chosen were the changes in FEV1 and PC20 due to the corticosteroid
      effect. Calculations were performed by extracting data from published placebo
      controlled trials, and defining a range of equivalence limits and differences
      between the group averages. It was shown that a huge number of volunteers (500
      1000) will be needed, as a result of the small corticosteroid effect and the high
      variance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589041
TI  - Pressor, renal and endocrine effects of L-arginine in essential hypertensives.
AB  - The pressor, renal and endocrine effect of the physiological precursor of
      endothelial derived nitric oxide, L-arginine was compared, with a substrate
      inactive on nitric oxide, hypertonic D-glucose, in hypertensive patients. Ten
      mild-moderate essential hypertensives were assigned to either L-arginine (n = 5)
      or D-glucose (n = 5). Substances were infused over 25 min at equiosmolal rates
      preceded and followed by saline infusion for 25 min. Blood pressure and heart
      rate were monitored at 3-min intervals, while hormonal and humoral variables,
      inulin and paraaminohippurate clearance and electrolyte excretion were measured
      at the end of each period under conditions of maximal diuresis. L-arginine and D
      glucose increased serum osmolality comparably and caused similar haemodilution to
      that with control saline. During L-arginine infusion, systolic and diastolic
      blood pressure decreased by 16.6% and 11%, respectively, and recovered in the
      postinfusion period. Heart rate, plasma renin activity, and plasma noradrenaline
      did not change significantly. The percent blood pressure decrement induced by L
      arginine was significantly greater than that by D-glucose. Glomerular filtration
      rate was stable and renal plasma flow was increased by both substances. However,
      natriuresis, kaliuresis and chloruresis were markedly stimulated only by L
      arginine, which also promoted the development of systemic acidosis, possibly as a
      consequence of hydrochloridric acid generated during its metabolism. Circulating
      insulin, atrial natriuretic peptide, growth hormone and glucagon levels were
      increased and plasma aldosterone was unchanged during infusion of L-arginine.
      Insulin was stimulated and the other hormones inhibited during infusion of D
      glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589040
TI  - Nicorandil suppressed myocardial purine metabolism during exercise in patients
      with angina pectoris.
AB  - To elucidate the effect of Nicorandil on myocardial energy metabolism and
      myocardial sympathetic activity, we administered Nicorandil orally to eight
      patients with angina pectoris prior to exercise testing. Arterial and coronary
      sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline
      were measured during exercise in order to determine the irrespective myocardial
      extraction ratios (MER). Compared to placebo, Nicorandil increased the time to
      development of significant ST depression (322 vs 390 s) while decreasing the
      maximum amplitude of ST depression (0.244 vs 0.216 mV). Heart rate, systolic
      blood pressure, and the rate pressure product during exercise were not
      significantly affected. The MER of lactate, measured during exercise, was
      significantly higher after Nicorandil than placebo (13.6 vs 27.9). Similarly, the
      MERs of ammonia and HX were significantly higher after Nicorandil (-46.0 vs 7.4%
      and -47.0 vs 9.9% respectively). Nicorandil, had no apparent effect on myocardial
      sympathetic activity as the MERs of adrenaline and noradrenaline were essentially
      unaffected. We conclude that Nicorandil decreased myocardial ischaemia and
      suppressed myocardial accelerated purine metabolism (a marker of cellular energy
      metabolism) during exercise in patients with angina pectoris. This effect appears
      not to be related to myocardial sympathetic activity.

PMID- 7589042
TI  - Effect of moxonidine on urinary electrolyte excretion and renal haemodynamics in
      man.
AB  - Moxonidine and related compounds have been recently introduced into
      antihypertensive therapy. It is thought that these drugs exert their blood
      pressure lowering effect through interaction with non-adrenergic receptors in the
      central nervous system, i.e. imidazoline receptors, although the contribution of
      specific interaction with alpha 2-receptors is still under debate. Imidazoline
      receptors have recently been documented in the renal proximal tubule. In
      experimental studies, interaction of imidazolines with these receptors decreased
      the activity of the Na+/H+ antiporter and induced natriuresis. To quantitate the
      effect of the imidazoline receptor agonist moxonidine on renal sodium handling
      and renal haemodynamics in man, we examined ten healthy normotensive males (age
      25 +/- 4 years) in a double blind placebo-controlled study using a crossover
      design. Subjects were studied on a standardized salt intake (50 mmol per day). On
      the 7th and 10th study day they were randomly allocated to receive either i.v.
      placebo or i.v. 0.2 mg moxonidine. Urinary electrolyte excretion, lithium
      clearance (as an index of proximal tubular sodium handling), glomerular
      filtration rate (GFR), effective renal plasma flow (ERPF), renal vascular
      resistance (RVR), mean arterial blood pressure (MAP), plasma renin activity (PRA)
      and plasma noradrenaline (NA) levels were assessed. Injection of moxonidine did
      not increase fractional sodium excretion or lithium clearance. Specifically,
      antinatriuresis was not observed after injection of moxonidine despite a
      significant decrease in MAP from 91 to 85 mmHg and a significant increase in
      PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589043
TI  - High-density lipoprotein and apolipoprotein A-I deficiency induced by combination
      therapy with probucol and bezafibrate.
AB  - The effects of the administration of slow-release bezafibrate to
      hypercholesterolaemic patients who were already receiving long-term probucol
      treatment (mean 865 days, 500-1000 mg.day-1) were investigated. Bezafibrate was
      administered at either 200 mg.day-1 (13 males, 13 females, mean age 55.2 years)
      or 400 mg.day-1 (11 males, 14 females, mean age 57.2 years), and blood was taken
      at 0, 3, 6 and 12 months after the beginning of combination therapy. Overall,
      serum total cholesterol (TC), triglyceride (TG), very low density lipoprotein
      (VLDL)-TC, high-density lipoprotein (HDL)-TG, VLDL-TG, VLDL-phospholipid (PL),
      lipoprotein (a) [Lp(a)], apolipoprotein (apo) C-III, apo E levels and LCAT
      activity decreased significantly with this combination therapy, while HDL
      cholesterol (C), HDL3-C, HDL-PL, apo A-I and apo A-II levels significantly
      increased, as assessed by analysis of variance (ANOVA). Five patients (one
      receiving 200 mg.day-1, four receiving 400 mg.day-1 bezafibrate) showed drastic
      reductions in HDL-C (HDL-C levels were reduced by a mean of 46.2%, 59.3% and
      61.6% at 3, 6 and 12 months, respectively) after beginning combination therapy.
      These HDL-C reductions were maintained for the 1 year of combination therapy, but
      then returned to pre-combination treatment levels 1 month after discontinuation
      of bezafibrate. Serum probucol concentrations and cholesteryl ester transfer
      protein (CETP) mass were assayed at 6 months, and the probucol concentration was
      higher in the HDL-deficient group (56.2 vs 26.5 micrograms/ml). In contrast, CETP
      mass was significantly lower in HDL-deficient patients than in non-HDL-deficient
      patients (2.08 vs 2.87 mg.1-1)(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589044
TI  - Does lowering of cholesterol levels influence functional properties of large
      arteries?
AB  - Hypercholesterolaemia is a risk factor for atherosclerosis and induces
      endothelial dysfunction. Endothelial dysfunction may increase vascular tone and
      arterial stiffness and as a consequence may decrease arterial distensibility (DC)
      and arterial compliance (CC). It is hypothesized that lipid-lowering therapy may
      enhance DC and CC. Therefore, the present study investigates the effect of lipid
      lowering therapy with pravastatin on the haemodynamics, DC and CC of the elastic
      common carotid artery (CCA), and the muscular femoral (FA) and brachial (BA)
      arteries in patients with primary hypercholesterolaemia. After an 8-week placebo
      run-in period with a low-cholesterol diet, 19 patients with total cholesterol
      concentrations of between 6.5 and 9.0 mmol.l-1 and triglyceride concentrations <
      4 mmol.l-1 entered a double-blind placebo controlled crossover study. Patients
      received pravastatin 40 mg o.d. or placebo, each for 8 weeks. Throughout the
      study the lipid-lowering diet was continued. With pravastatin, total cholesterol,
      low-density lipoprotein cholesterol (LDL-C) and triglycerides were decreased
      (total cholesterol 26%, LDL-C 35%, triglycerides 16%), while high-density
      lipoprotein cholesterol (HDL-C) was not changed. Other laboratory values remained
      within the normal range. Blood pressure, heart rate, cardiac function and
      systemic vascular resistance were not influenced by pravastatin. Compared to
      placebo, diameter, distensibility and compliance of all arteries were not
      statistically significantly changed with pravastatin. These data suggest that, in
      patients with mild to moderate primary hypercholesterolaemia, short-term lowering
      of plasma cholesterol does not alter the haemodynamics and vessel wall properties
      of large arteries.

PMID- 7589045
TI  - The characteristics of the inhibition of serum cholinesterase by metoclopramide.
AB  - The inhibition of serum cholinesterase by metoclopramide has been previously
      characterised in vitro at high dilution of the enzyme. We examined the effect of
      varying enzyme dilution over a range of 1000 fold dilution, and assay temperature
      at 25 degrees C and 37 degrees C on the fractional inhibition of enzyme activity
      by metoclopramide. Neither enzyme concentration nor reaction temperature affected
      this fractional inhibition. Concentrations of metoclopramide producing 50%
      inhibition of enzyme activity were in the range 1.0-1.9 x 10(-6) M. Lineweaver
      Burk analysis of the enzyme reaction suggests that the pattern of this inhibition
      is competitive.

PMID- 7589047
TI  - Effect of nicotine vapour inhalation on the relief of tobacco withdrawal
      symptoms.
AB  - Fifteen subjects participated in a randomised, placebo-controlled cross-over
      study to assess the effect of a nicotine vapour inhaler on craving and other
      withdrawal symptoms during a two-day smoking-free period. Craving and withdrawal
      symptoms were rated nine times over the two-day period on 10 cm visual analogue
      scales. Plasma nicotine concentrations in the afternoon of each study day were
      determined. The results show that active treatment was significantly superior to
      placebo in decreasing craving and other withdrawal symptom scores. No difference
      was found between two inhalation techniques, one with shallow, frequent
      inhalations (buccal technique), and the other with deep inhalations (pulmonary
      technique). The average number of active nicotine vapour inhalers and placebo
      inhalers used during the two-day sessions was 12 and 11, respectively. Afternoon
      plasma nicotine levels of approximately 7 ng/ml were obtained with both
      inhalation techniques. A strong correlation was found between the afternoon
      plasma nicotine levels and craving, a high nicotine level being associated with a
      low craving score. The study has provided information about how to use the
      nicotine vapour inhaler that could have important implications if it were to be
      approved for the treatment of tobacco dependence. The use of withdrawal symptom
      reduction as a surrogate end-point is discussed.

PMID- 7589049
TI  - Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in
      healthy volunteers.
AB  - Fifteen healthy male volunteers participated in an open, multiple-dose study to
      investigate a possible interaction between furosemide and meloxicam, a new non
      steroidal anti-inflammatory agent (NSAID). The study comprised three treatment
      periods. First, furosemide (40 mg) was administered as a single oral daily dose
      for 3 days. A wash-out day was followed by the administration of meloxicam (15
      mg) as a single oral daily dose for 10 days. Thereafter, meloxicam and furosemide
      were administered concomitantly at the same doses as described above, for 3 days.
      The effect of concomitant ingestion of meloxicam and furosemide on furosemide
      induced diuresis, urine and serum electrolytes, and furosemide pharmacokinetics
      was determined, after both single and repeated administration of furosemide.
      Estimates of the "(furosemide+meloxicam)/(furosemide alone)" mean ratio of the
      variable AUC(0-infinity) for plasma furosemide and the cumulative sodium
      excretion (0-8 h) were 97.4% (90% confidence interval 89.7-106%) and 88% (90%
      confidence interval 82-94%), respectively. The study results indicate that
      meloxicam does not affect the pharmacokinetics of furosemide in healthy
      volunteers, nor does it affect furosemide-induced diuresis or serum electrolytes.
      The cumulative urinary electrolyte excretion after concomitant administration of
      meloxicam and furosemide is somewhat lower than after administration of
      furosemide alone, in particular for the period 0-8 h after administration of
      furosemide. This effect of meloxicam on furosemide dynamics is small, and is
      probably not clinically relevant in healthy volunteers under the dosing regime
      studied.

PMID- 7589046
TI  - Effect of combined atenolol and nifedipine administration on psychomotor
      performance in normal subjects.
AB  - The aim of the present study was to evaluate the central effects of single doses
      of the beta-adrenoceptor antagonist atenolol and the calcium antagonist
      nifedipine retard, alone and in combination, in normal subjects. Twelve normal
      males received single oral doses of atenolol 100 mg, nifedipine retard 20 mg,
      atenolol 100 mg and nifedipine retard 20 mg in combination, diazepam 5 mg (active
      control), and each of two matching placebos in a double-blind, randomised
      fashion. Psychomotor performance was assessed using digit symbol substitution,
      letter cancellation (LCT), continuous attention, choice reaction time, finger
      tapping, immediate recall and short-term memory. Two flash fusion and critical
      flicker fusion thresholds were measured and subjective assessments made using
      visual analogue scales (VAS). Diazepam 5 mg significantly worsened LCT scores at
      4h, significantly impaired alertness at 2 h and 4 h, and tended to increase
      reaction time and impair continuous attention and physiological measurements.
      Atenolol 100 mg alone significantly reduced alertness at 2 h and 4 h, and also
      tended to impair physiological measurements. Nifedipine retard 20 mg produced no
      significant psychomotor effects. Combined atenolol and nifedipine retard
      administration produced a small but significant improvement in continuous
      attention and a reduction in body sway, with no adverse effects being evident on
      performance or subjective awareness. The results suggest that no significant
      adverse effects on psychomotor performance are produced by single doses of
      atenolol 100 mg and nifedipine retard 20 mg when given together in normal
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589048
TI  - Influence of piroxicam coadministration on pharmacodynamic parameters and the
      plasma concentration/effect relationship of recombinant hirudin (CGP 39393).
AB  - Recombinant hirudins are currently under investigation for use in myocardial
      infarction and unstable angina. In this study the influence of piroxicam on the
      pharmacodynamics and pharmacokinetics of a recombinant hirudin preparation (CGP
      39393) administered intravenously was determined. Twelve healthy, male volunteers
      received piroxicam 10 mg and matching placebo once daily for 12 days according to
      a double-blind, randomised cross-over design. On the 12th day, the dose of
      piroxicam was followed by a 6-hour infusion of hirudin 0.1 mg.kg-1.h-1. Plasma
      concentrations and urinary excretion of hirudin and repeated measurements of the
      activated partial thromboplastin time (APTT), bleeding time and platelet adhesion
      index were assessed up to 24 h after the start of the infusion. The maximum APTT
      was 83 s (placebo) and 84 s (piroxicam), 3 to 4 h after the start of the
      infusion, and was comparable on both study days. The AUD0-24 (APTT) came to 913
      s.h.kg-1 under placebo and it was slightly increased to 1,017 s.h.kg-1 after
      piroxicam; the 95%- confidence interval according to MOSES ranged from 0.97 to
      1.24, and the point estimator was 1.10. Bleeding time was significantly prolonged
      from 290 s under placebo to 345 s under piroxicam before the start of the
      infusion of hirudin. No further prolongation was found during or after the
      infusion. No change was observed in the platelet adhesion index. Responsiveness
      parameters according to a sigmoidal Emax-model were obtained from the hirudin
      plasma concentration/effect (i.e. APTT-prolongation)-curves after placebo and
      piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589053
TI  - The effect of cholestyramine on the pharmacokinetics of meloxicam, a new non
      steroidal anti-inflammatory drug (NSAID), in man.
AB  - The influence of multiple oral doses of cholestyramine on the single dose
      pharmacokinetics of meloxicam has been studied in 12 healthy male volunteers.
      Each subject received on two occasions a single IV injection of meloxicam 30 mg.
      The cholestyramine group received the material suspended in water 3 times a day.
      Compared to controls, cholestyramine accelerated the elimination of meloxicam.
      The mean terminal phase elimination half-life was reduced from 19.5 h to 12.7 h
      due to an increase in clearance of the drug (0.426 vs 0.636 l.h-1). Also, as a
      consequence of increased clearance in the presence of cholestyramine, the mean
      residence time of the drug in the body was significantly decreased (39%) P <
      0.01. However, the volume of distribution for meloxicam was largely unaffected by
      cholestyramine which suggests that meloxicam undergoes gut recirculation. These
      changes are of the same magnitude as those previously reported for the
      structurally related piroxicam and are much smaller than those observed for
      tenoxicam.

PMID- 7589051
TI  - Pharmacokinetics and bioavailability of a sustained-release diltiazem formulation
      (Mono-Tildiem LP 300 MG) after repeated administration in healthy volunteers.
AB  - The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3-4 times a day. A
      sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in
      order to allow a single daily administration. Two repeated dosing studies were
      performed in healthy volunteers. The absolute bioavailability of sustained
      release diltiazem LP 300 mg was investigated using concomitant i.v.
      administration of 13C-labelled drug: absolute bioavailability of the "once a day"
      formulation was 35%. The second study compared sustained-release diltiazem LP 300
      mg with the standard formulation of diltiazem. The results showed that the
      diltiazem plasma concentrations obtained after the LP formulation remained stable
      between 2 and 14 h after administration and were compatible with a once a day
      administration. Relative bioavailability of sustained-release diltiazem LP 300 mg
      was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release
      diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose
      administered with the standard diltiazem formulation.

PMID- 7589052
TI  - Effects of liver disease on the pharmacokinetics of intravenous and oral
      chlordesmethyldiazepam.
AB  - We studied the pharmacokinetics of a single 0.5-mg i.v. dose of
      chlordesmethyldiazepam in 8 patients with liver disease and in 12 age-matched
      healthy controls. The kinetics were also studied of a single 1-mg oral dose in
      the patients with liver disease. After i.v. administration the kinetics of total
      chlordesmethyldiazepam in patients with liver disease differed from those in
      controls: elimination half-life was almost twice that in controls (395 and 204
      h), as a consequence of a marked reduction in total clearance (0.13 and 0.25
      ng.ml-1.h-1), whereas the apparent volume of distribution was similar in patients
      and controls (4.7 and 3.9 l/kg-1). The free fraction of the drug in patients was
      higher (5.5%) than in controls (2.9%). Correction for differences in protein
      binding revealed clearance in the patients was one-fifth (1.8 and 10.5 ng ml-1.kg
      1) and volume of distribution one-half (65.0 and 118.4 l.kg-1) that in controls.
      The systemic availability of oral chlordesmethyldiazepam was high (110%) in spite
      of a relatively slow absorption rate. These results indicate a need for caution
      in the administration of chlordesmethyldiazepam to patients with liver disease.

PMID- 7589050
TI  - Disposition of lorazepam in diabetes: differences between patients treated with
      beef/pork and human insulins.
AB  - The pharmacokinetics of lorazepam was examined in 10 male patients with insulin
      dependent diabetes mellitus before and following treatment with neomycin and
      cholestyramine. Neomycin and cholestyramine were given in an attempt to block the
      enterohepatic circulation of lorazepam and so to permit an in vivo estimate of
      hepatic glucuronidation. The volume of distribution and clearance of free
      lorazepam in diabetic patients were not significantly different from the
      corresponding estimates in 14 normal controls. Neomycin and cholestyramine
      increased the clearance of lorazepam by 63% consistent with their effect in non
      diabetic controls. However, patients on beef/pork insulin exhibited a greater
      than normal increase on this interupting regimen (125%), and had a significantly
      greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than
      either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87
      ml.min-1.kg-1). The clearance was correlated positively and significantly with
      HbA1c and glycated proteins (fructosamine), but only in patients on human
      insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with
      insulin-dependent diabetes mellitus. However, it is possible that there are
      differences in the rate and extent of hepatic glucuronidation and enterohepatic
      circulation of lorazepam between patients treated with beef/pork and human
      insulins and between diabetics treated with beef/pork insulin and non-diabetic
      controls.

PMID- 7589054
TI  - Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in
      man.
AB  - One gram single dose of Pentasa controlled-release capsules was administered to
      24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid
      (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 microgram.ml-1 and 1.33
      micrograms.ml-1 from 3 to 4 hours following dosing, respectively. The half-lives
      of both compounds could not be determined as absorption of 5-ASA was continuous
      throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose
      was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was
      released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in
      the feces, with 8.9% of the dose remained as formulation bounded 5-ASA,
      indicating that controlled-release capsules continue to release drug throughout
      the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces
      and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced
      three times more total salicylates and 10 times more total and free 5-ASA in the
      feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates
      were absorbed, greater therapeutic quantities of 5-ASA were available in the
      bowel.

PMID- 7589057
TI  - Pharmacokinetics of fluconazole after oral administration in children with human
      immunodeficiency virus infection.
AB  - The objective of this study was to determine the pharmacokinetics of fluconazole
      after oral administration in children with human immunodeficiency virus (HIV)
      infection. After an overnight fast, a single dose of either 2 mg.kg-1 or 8 mg.kg
      1 was administered in a suspension; five children received 2 mg.kg-1 and four 8
      mg.kg-1 (ages 5-13 years). Blood samples were collected at various times on day
      1, and once daily on days 2-7 after the dose. Fluconazole serum concentrations
      were measured by gas chromatography. At the dose of 2 mg.kg-1, the Cmax, AUC (0
      infinity), and t1/2 ranged from 2.3-4.4 micrograms.ml-1, 84.9-136 micrograms.h.ml
      1, and 19.8-34.8 h, respectively. At the dose of 8 mg.kg-1 the Cmax, AUC (0
      infinity), and t1/2 ranged from 5.4-12.1 micrograms.ml-1, 330-684 micrograms h.ml
      1, and 25.6-42.3 h, respectively. When compared with published data in healthy
      adults, fluconazole achieved similar serum concentrations in the present group of
      children, indicating a nearly complete degree of absorption.

PMID- 7589058
TI  - Influence of vitamin C on the absorption and first pass metabolism of
      propranolol.
AB  - The effect of ascorbic acid on the availability of propranolol has been examined.
      After oral administration of propranolol 80 mg with or without ascorbic acid
      pretreatment (2 g), the plasma concentrations and urinary excretion of
      propranolol and its metabolites, 4-hydroxy-propranolol and propranolol
      conjugated, were determined by HPLC. Compared to controls, vitamin C decreased
      the maximum concentration of propranolol from 463 to 334 nmol.l-1, and the area
      under the propranolol concentration-time curve (from 0 to 24 hours) from 3.13 to
      1.96 mumol.l-1.h. The time to reach maximum propranolol concentration was
      increased from 1.9 to 2.7. The total amount of drug recovered in urine has also
      significantly diminished (from 12.6 to 4.29 mg). No change in elimination rate
      was observed, indicating that ascorbic acid had affected both the absorption
      process and the first pass metabolism. The heart-rate decreased less when
      propranolol was administered with ascorbic acid in comparison to control
      subjects, although this interaction has little biological importance.

PMID- 7589056
TI  - Relative bioavailability of cyclosporin from conventional and microemulsion
      formulations in heart-lung transplant candidates with cystic fibrosis.
AB  - Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have
      compared the relative bioavailability of cyclosporin from conventional and
      microemulsion formulations in 5 adult heart-lung transplant candidates with
      cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg
      and 800 mg). A randomized 4-period cross-over study was performed with at least a
      7 day washout period between each single dose pharmacokinetic study. Blood
      cyclosporin concentrations were measured by a selective monoclonal antibody-based
      radioimmunoassay. The bioavailability of cyclosporin from the microemulsion
      formulation was 1.84 (95% C.I. 1.05 to 3.22; P = 0.04) and 2.09 (95% C.I. 0.95 to
      4.61; P = 0.06) times higher compared with the conventional formulation at 200 mg
      and 800 mg respectively. Cmax following the microemulsion formulation was 3.38
      (C.I. 1.14 to 10.59; P = 0.04) and 2.77 (C.I. 1.48 to 5.19; P = 0.01) times
      higher compared with the conventional formulation at 200 mg and 800 mg
      respectively. The higher Cmax following the microemulsion formulation was
      accompanied by shorter tmax. An enhancement of cyclosporin absorption with the
      microemulsion formulation was demonstrated in each patient for at least one dose
      level. We conclude that rate and extent of cyclosporin absorption from the
      microemulsion formulation is greater compared with the conventional formulation
      in patients with cystic fibrosis. The potential therapeutic and economic benefits
      of the microemulsion formulation should be evaluated in cystic fibrosis patients
      following heart-lung transplantation.

PMID- 7589059
TI  - Changes in the use of antibacterial drugs in the countries of central and eastern
      Europe.
AB  - Use of systemic antibacterial drugs in the countries of central and eastern
      Europe (CCEE) has been studied using the defined daily doses (DDD) methodology.
      For the comparison, national wholesale data from Bulgaria, the Czech Republic,
      Estonia, Hungary, Lithuania, Slovakia, Slovenia and Romania for the years 1989
      and 1992 were used, i.e. for the years before and after the rapid sociopolitical
      changes in these countries. Substantial differences in the patterns of
      antibacterial drug use between countries as geographically and economically
      similar as the CCEE were observed. The general sales of antibiotics varied almost
      twofold among the CCEE and had decreased in most of the CCEE during the study
      period. The proportion of tetracyclines in the sales of 1992 ranged from 10% in
      Slovenia to 49% in Estonia, and that of broad-spectrum penicillins from 6% in
      Estonia to 40% in Slovenia. The use of narrow-spectrum penicillins varied within
      the range of 4% in Bulgaria to 38% in Slovakia, and had decreased during the
      study years in all countries. Aminoglycosides accounted for 5-12% of all
      antibacterials in Bulgaria, Estonia, Lithuania, Romania and Slovakia in the study
      period, and these countries, with the exception of Slovakia, also had a high
      consumption of chloramphenicol. In 1992, by far the most popular antiinfectives
      in the CCEE were doxycycline, ampicillin and co-trimoxazole, which ranked among
      the top ten drugs in all countries studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589055
TI  - Influence of renal function on the steady-state pharmacokinetics of the
      antiarrhythmic propafenone and its phase I and phase II metabolites.
AB  - The aim of this study was to investigate the disposition of propafenone and its
      Phase I and II metabolites in relation to kidney function under steady-state
      conditions. The mechanism of the renal handling of propafenone glucuronides
      (filtration, secretion) was also examined. Racemic (R/S) propafenone was
      administered to 7 young volunteers, to 5 older patients with a normal glomerular
      filtration rate and to 4 patients with chronic renal failure. No difference was
      found in the plasma concentrations of propafenone and 5-hydroxypropafenone
      between the three groups. The propafenone glucuronide (PPFG) concentration was
      elevated in the older compared to the younger subjects (S-PPFG: 544 vs. 222
      nmol.ml-1.mol-1; R-PPFG: 576 vs. 304 nmol.ml-1.mol-1). Although Glomerular
      filtration rate did not differ, the renal clearance of propafenone glucuronides
      was reduced in the former group, which could be attributed to their impaired
      renal secretion. A dramatic increase in propafenone glucuronide concentration was
      observed in the patients with renal failure (S-PPFG: 2783 nmol.ml-1.mol-1; R
      PPFG: 7340 nmol.ml-1.mol-1). In summary, the disposition of propafenone and of
      its active metabolite 5-hydroxypropafenone was not affected by kidney
      dysfunction, indicating that no dose adjustment is necessary in patients with
      renal failure. The accumulation of drug glucuronides in older patients with
      apparently normal kidney function should be taken into account as a possible
      factor modifying drug therapy.

PMID- 7589061
TI  - Azathioprine toxicity, 6-mercaptopurine accumulation and the "poor" 6-thiopurine
      methylator phenotype.

PMID- 7589060
TI  - Red cell folate levels in pregnant epileptic women.
AB  - Red cell folate concentrations were determined in 74 epileptic women in early
      pregnancy in a prospective study. All patients were treated continuously with
      antiepileptic drugs since before conception. The most frequently used drugs were
      carbamazepine (n = 39) and phenytoin (n = 26). Sixty-four patients (86%) were on
      monotherapy. Blood samples for red cell folate and antiepileptic drug
      concentrations were drawn before folate supplementation. Red cell folate levels
      in patients, 468 nmol.l-1, did not differ from those in non-epileptic, drug-free,
      pregnant women, 416 nmol.l-1 or from those in non-pregnant age-matched healthy
      controls, 412 nmol.l-1. No correlation was found between red cell folate
      concentrations and doses or plasma levels of phenytoin or carbamazepine.

PMID- 7589062
TI  - Secondary prevention of myocardial infarction: impact of clinical trials on
      clinical practice.

PMID- 7589064
TI  - HLA class II-restricted recognition of common tumor epitopes on human melanoma
      cells by CD4+ melanoma-infiltrating lymphocytes.
AB  - CD4+ T cell clones derived from lymphocytes infiltrating four human melanomas
      specifically recognized melanoma-derived tumor epitopes as shown by secretion of
      tumor necrosis factor (TNF) in vitro upon interaction with autologous melanoma
      cells, whereas they did not recognize HLA class II-expressing autologous
      lymphoblasts or HLA class II mismatched allogeneic melanoma cells. Specificity
      was further established by demonstrating that TNF responses to tumor cells were
      inhibited by HLA-DR or HLA-DQ monoclonal antibodies. Most of these clones cross
      reacted with allogeneic melanoma cells expressing a potentially restricting HLA
      allele or a structurally similar one. These data show that shared epitopes of
      human melanoma cells presented on HLA class II molecules are frequently
      recognized by autologous CD4+ T lymphocytes.

PMID- 7589065
TI  - A B7-1-transfected human melanoma line stimulates proliferation and cytotoxicity
      of autologous and allogeneic lymphocytes.
AB  - B7 co-stimulation is necessary to activate resting T cells upon antigen
      recognition by the T cell receptor. To see whether expression of B7 may render
      human melanoma cells able to stimulate T cells, a cloned melanoma line (Me1B6),
      which did not express B7-1, was transfected with the human B7-1 gene. In
      proliferation assays, B7-1 transfected cells (Me1B6/B7) showed greater
      stimulatory activity of allogeneic and autologous peripheral blood lymphocytes
      (PBL) compared to parental, non-transfected tumor cells. This effect was also
      seen when allogeneic CD8+ and CD4+ subpopulations were used as effectors. In
      these studies, activation of lymphocytes was B7-1-dependent and HLA classes I and
      II mediated. The higher proliferation correlated with an increased lytic activity
      by PBL stimulated with B7-1+ tumor cells against the untransfected Me1B6.
      Furthermore, PBL from a metastatic melanoma patient stimulated by Me1B6/B7
      developed an higher lytic activity not only against Me1B6 but also against their
      autologous, B7-1- tumor. Finally, after Me1B6/B7 stimulation, PBL released
      interleukin (IL)-2 and interferon-gamma, but not IL-4, suggesting a Th1-mediated
      response. These data support the use of B7-1 transfected melanoma cells in the
      therapeutic vaccination of melanoma patients.

PMID- 7589063
TI  - Secretion of the eosinophil-active cytokines interleukin-5,
      granulocyte/macrophage colony-stimulating factor and interleukin-3 by
      bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and
      atopic and non-atopic controls.
AB  - Specific eosinophil accumulation and activation within the asthmatic bronchial
      mucosa are thought to occur at least partly through the actions of cytokines,
      including interleukin (IL)-5, IL-3 and granulocyte/macrophage colony-stimulating
      factor (GM-CSF). Although mRNA encoding some of these cytokines has been
      demonstrated in bronchoalveolar lavage (BAL) fluid cells and bronchial biopsies
      from asthmatics, it has yet to be established whether these cells produce the
      translated products and whether expression is associated with CD4+ T helper or
      CD8+ cytotoxic T cells. We addressed this problem by raising polyclonal CD4+ and
      CD8+ T cell lines from the BAL fluid of six atopic asthmatics, five atopic non
      asthmatics and seven non-atopic non-asthmatic controls. BAL fluid cells obtained
      at fiberoptic bronchoscopy were depleted of adherent cells, and then T
      lymphocytes expanded by stimulation with monoclonal anti-CD3 antibody and
      recombinant human IL-2. When lymphocytes had expanded to sufficient numbers, CD4+
      and CD8+ cells were separated by positive selection with magnetic beads coated
      with anti-CD4 or anti-CD8 monoclonal antibodies and further expanded. Cytokine
      secretion by standardized cell numbers was measured by enzyme-linked
      immunosorbent assays. BAL CD4+ T cell lines from the asthmatics secreted
      significantly elevated quantities of both IL-5 and GM-CSF as compared with lines
      from the atopic and non-atopic controls (p = 0.023-0.003). In contrast, IL-3
      secretion did not significantly differ between the groups. In some subjects, CD8+
      T cell lines also secreted significant quantities of these cytokines and there
      was a trend for IL-5 secretion by these cells to be higher in asthmatics than non
      atopic controls (p = 0.035). These data are consistent with the hypothesis that
      activated T lymphocytes from asthmatics, particularly of the CD4+ subset, are
      predisposed to release elevated quantities of cytokines relevant to the
      accumulation and activation of eosinophils.

PMID- 7589066
TI  - Polarized Th2 cytokine expression by both mucosal gamma delta and alpha beta T
      cells.
AB  - Currently only limited information is available as to why dominant IgA isotype
      responses are supported by mucosal T cells in effector tissues. To address this
      issue directly, gamma delta and alpha beta T cells were isolated from the
      submandibular gland (SMG) of mice as an example of mucosal effector tissues.
      Freshly isolated CD3+ T cells from this tissue contained relatively high numbers
      of activated cells [approximately 10% interleukin-2 receptor (IL-2R)+ cells and
      15% of cells in cycle stages S and G2 + M], of which 25% and 75% were gamma delta
      and alpha beta T cells, respectively. The cytokine-specific quantitative reverse
      transcriptase-polymerase chain reaction and enzyme-linked immunospot analyses
      revealed that, although both gamma delta and alpha beta T cells were capable of
      producing an array of Th1 or Th2 cytokines following stimulation via the T cell
      receptor-CD3 complex, these mucosal T cells were mainly committed to IL-5 and IL
      6 expression in vivo (Th2 type). Both freshly isolated gamma delta and alpha beta
      T cells expressed mRNA and contained IL-5 and IL-6 spot-forming cells (SFC);
      however, only the latter exhibited high mRNA levels and SFC for a Th1 cytokine
      (interferon-gamma). Taken together, the results show that freshly isolated CD3+ T
      cells from SMG contain activated gamma delta and alpha beta T cells which are
      programmed to produce IL-5 and IL-6. Thus, SMG, an example of an IgA effector
      tissue, can be characterized as a Th2-dominant site. However, although both gamma
      delta and alpha beta T cells express cytokine profiles consistent with a Th2
      phenotype, only the latter subset with a CD4+ CD8- phenotype provided effective
      help for mucosal B cell responses in vitro.

PMID- 7589067
TI  - Emergence in C kappa knockout mice of a diverse cytotoxic T lymphocyte repertoire
      that recognizes a single peptide from the immunoglobulin constant kappa light
      chain region.
AB  - Allotype- or idiotype-specific CD4+ T cells have been reported to recognize
      immunoglobulin (Ig) peptides presented by class II molecules. In contrast, few
      data are available concerning the generation of Ig peptide-specific CD8+ T cells.
      We have therefore investigated whether T-depleted spleen cells from Ig kappa
      light chain-expressing 129/Sv mice (129 kappa +/+) could induce, in C kappa
      knockout mice (129 kappa -/-), the generation of Ig constant kappa light chain
      region (C kappa)-specific cytotoxic T lymphocytes (CTL). The determination of TCR
      beta chain expressed by nine CTL clones, together with the use of a library of
      overlapping peptides spanning the whole C kappa sequence, show that the B cells
      from kappa +/+ mice are able to elicit in C kappa knockout mice, the emergence of
      a diverse CTL repertoire that recognizes one single C kappa peptide presented by
      the H-2Kb class I molecule. In addition, these data support the notion that B
      cells are able to process and present on their class I molecules, peptides
      generated from their own kappa light chains.

PMID- 7589068
TI  - Internalization of B cell and pre-B cell receptors is regulated by tyrosine
      kinase and phosphatase activities.
AB  - Prior to the expression of the B cell antigen receptor, the mu heavy chain
      associates with two non-polymorphic polypeptides, lambda like and VpreB, which
      form a pseudo-light chain complex in pre-B cells and pre-B cell lines. Surface
      expression of the so-called pre-B cell receptor (pre-BCR) occurs only in the
      presence of Ig alpha and Ig beta, known to be involved both in B cell antigen
      receptor (BCR) signaling and trafficking. Although the pre-BCR organization is
      consistent with an efficient transport to the cell surface, most of the newly
      synthesized receptor remains within the cells, and so far, no data are available
      concerning the rate of exit from the endoplasmic reticulum. Using the human pre-B
      cell line Nalm-6, we found that only a small fraction (2%) of newly synthesized
      pre-BCR is transported to the cell surface within 4-6 h after synthesis, where it
      is constitutively re-internalized. Membrane Ig-heavy chain cross-linking induced
      internalization of surface pre-BCR within a few minutes, and the mechanisms
      underlying endocytosis were analyzed by immunofluorescence and confocal
      microscopy. Preincubation of the cells with either genistein or orthovanadate,
      which inhibit, respectively, tyrosine kinases and tyrosine phosphatases, blocked
      pre-BCR internalization in a dose-dependent manner, indicating that both
      activities are required for endocytosis. BCR internalization was also inhibited
      in a reversible manner by the drugs. In contrast, neither drug affected the size
      of the steady-state pool of internalized transferrin receptors. Thus, our data
      show that tyrosine phosphorylation and dephosphorylation are both required for
      cross-linking-induced pre-BCR and BCR internalization.

PMID- 7589069
TI  - Human CD6 possesses a large, alternatively spliced cytoplasmic domain.
AB  - Human CD6 is a monomeric 105/130-kDa T cell surface glycoprotein that is involved
      in T cell activation. The apparent discrepancy between the size of the
      cytoplasmic domain in human (44 amino acids) and mouse (243 amino acids) CD6, led
      us to use reverse transcriptase-polymerase chain reaction of human peripheral
      blood lymphocyte mRNA to isolate cDNA clones that include the carboxyl-terminal
      coding region of human CD6. The nucleotide sequence of the longest human cDNA
      clone, CD6-PB1, predicts a protein of 668 amino acids with a 244-amino acid
      cytoplasmic domain similar in size to and possessing 71.5% amino acid sequence
      identity with the cytoplasmic domain of mouse CD6. This previously unrecognized
      244-amino acid cytoplasmic domain does not have significant homology to any other
      known protein (except mouse CD6), but does possess two proline-rich motifs
      containing the SH3 domain-binding consensus sequence, a serine-threonine-rich
      motif repeated three times, three protein kinase C phosphorylation-site motifs,
      and 10 casein kinase-2 phosphorylation-site motifs. These sequences are likely to
      play a role in the ability of CD6-specific monoclonal antibodies to stimulate T
      cell proliferation. Full-length CD6 cDNA containing this cytoplasmic domain
      sequence encodes a monomeric 105/130-kDa protein that can be immunoprecipitated
      from the surface of transfected cells and comigrates upon SDS-PAGE with wild-type
      CD6 immunoprecipitated from PBL. We also isolated two alternatively spliced forms
      of human CD6 cDNA lacking sequences encoding membrane-proximal regions of the
      cytoplasmic domain which maintain the same reading frame as CD6-PB1. The short
      cytoplasmic domain of the previously reported human CD6-15 cDNA clone results
      from a deletion of a 20-bp segment through use of an alternative 3' splice site,
      resulting in a frame shift and premature termination of translation relative to
      the clones we have isolated. These data demonstrate that human CD6 possesses a
      large cytoplasmic domain containing sequence motifs that are likely to be
      involved in signal transduction upon stimulation of T cells through CD6 ligation.

PMID- 7589070
TI  - Abundance of H-2 promiscuous T cells specific for mycobacterial determinants in H
      2b/d F1 hybrid mice.
AB  - A majority of immunodominant epitopes of mycobacterial antigens are known to be
      recognized by murine T cells in the context of several H-2 haplotypes. In this
      study, we established the frequency of T cells able to recognize these peptides
      promiscuously, i.e. in the context of allogeneic antigen-presenting cells, using
      hybridomas from peptide-immunized H-2 homologous and heterologous mice. The
      degree of promiscuity in homozygous mice varied between 4-27% between different
      specificities and genetic backgrounds. In particular, the results showed that
      promiscuity between Ab and Ad in respect to a peptide from the Mycobacterium
      tuberculosis 38-kDa protein (residues 350-369) was displayed by 22% of BALB/c and
      4% of C57BL/10-derived hybrids, but by 42% of [BALB/c x C57BL/10] F1-derived
      clones. This represents a significant increase (p < 0.001) of T cell promiscuity
      compared to the parental haplotypes. It is noteworthy that considerably lower
      peptide concentrations were able to stimulate the promiscuous hybridomas compared
      to the H-2-restricted hybrids. This finding suggests a functional advantage of
      promiscuous T cells which enables them to expand preferentially in the initial
      stages of infections with M. tuberculosis and thus enables the host to mount a
      rapid protective immune response.

PMID- 7589071
TI  - The B lymphocyte in rheumatoid arthritis: analysis of rearranged V kappa genes
      from B cells infiltrating the synovial membrane.
AB  - The participation of the humoral immune system in rheumatoid arthritis (RA) is
      characterized by the production of rheumatoid factors (RF). RF are autoantibodies
      against the Fc part of IgG which are encoded by diverse germ-line genes. Most of
      the RF-encoding genes are unmutated, but in RA, a substantial quantity is encoded
      by somatically mutated genes. In addition, the synovial membranes (SM) of the
      diseased joints of RA patients are infiltrated by B lymphocytes which form
      germinal center-like aggregates. To analyze the local immune response, B cell
      foci from two RA SM were isolated by micromanipulation. From DNA of these foci,
      the rearranged kappa light chain variable region (V kappa) genes were amplified
      by polymerase chain reaction (PCR), cloned and sequenced. The amplification of
      different V kappa-J kappa combinations of different foci suggested oligoclonal
      expansion of B lymphocytes, which was confirmed by sequence analysis: each PCR
      product contained members of a single B cell clone. The sequence analysis of 29
      different clones revealed rearrangements of diverse V kappa genes. Both frequent
      representatives of the V kappa 3 and the V kappa 1 family, as well as rarely used
      genes such as the L10 and B2 genes of the V kappa 2 and V kappa 5 families were
      found. Of the eleven potentially functional gene rearrangements, eight were
      significantly mutated, indicating their derivation from antigen-selected B cells.
      Intraclonal diversity in one of these clones may suggest ongoing mutation in the
      diseased synovial membrane of patients with RA.

PMID- 7589072
TI  - Role of splenic B cells in the immune privilege of the anterior chamber of the
      eye.
AB  - The immune privilege of the anterior chamber (AC) of the eye is largely due to
      the active down-regulation of systemic delayed-type hypersensitivity (DTH) that
      is evoked when antigens are introduced into this ocular compartment. This antigen
      specific suppression of DTH has been termed anterior chamber-associated immune
      deviation (ACAID) and has been demonstrated with a wide variety of antigens.
      Previous studies have shown that antigens introduced into the AC are processed by
      resident antigen-presenting cells which then migrate to the spleen where they
      transmit a signal that culminates in the generation of regulatory cells that
      prevent the development of DTH. Although considerable effort has focused on the
      nature of the ocular phase of ACAID, the role of the spleen has been largely
      ignored. The present study tested the hypothesis that B cells are the essential
      cell population responsible for the splenic phase of ACAID. Splenectomy prevented
      the induction of ACAID; however, introduction of B cell-enriched spleen cells
      into the AC of splenectomized mice restored the hosts' capacity to develop ACAID.
      The same effect, however, could not be produced with B cell-depleted spleen
      cells. B cell depletion of eusplenic mice by chronic administration of anti-mu
      antiserum prevented the development of ACAID and thus, had the same of effect as
      splenectomy. The results indicate that an intact B cell population is necessary
      for the induction of ACAID. These findings also support the hypothesis that
      antigens arising in the AC and subsequently delivered to spleen are captured by B
      cells and presented to T cells in a manner that promotes the development of down
      regulatory T cells.

PMID- 7589074
TI  - CD8+ cell activation to a major mastocytoma rejection antigen, P815AB:
      requirement for tum- or helper peptides in priming for skin test reactivity to a
      P815AB-related peptide.
AB  - Delayed-type hypersensitivity (DTH) responses, mediated by CD8+ cells and
      detected by skin test assay, occur in sensitized mice in response to challenge
      with class I-restricted antigenic peptides of mutagenized (tum-) P815 mastocytoma
      cells. In contrast, a nonapeptide related to a tumor rejection antigen, P815AB,
      failed in this study to elicit DTH after sensitization of mice with irradiated
      tumor cells or adoptive transfer of P815AB-pulsed dendritic cells.
      Unresponsiveness, however, could be overcome by immunization with tumor cells co
      expressing P815AB and tum- antigens. When used for cell pulsing in vitro, a
      mixture of P815AB and tum- peptides was also highly effective in inducing anti
      P815AB reactivity, as was the combined use of P815AB and class II-restricted
      peptides of tetanus toxin or Plasmodium berghei circumsporozoite protein. While
      the effector phase of the CD8+ cell-mediated DTH to P815AB was unaffected by the
      ablation of CD4+ cells, the same treatment, or neutralization of IFN-gamma,
      negated the induction of reactivity if it occurred at the time of sensitization.
      Thus, defective activation of CD4+ cells may contribute to the poor
      immunogenicity of P815AB. Besides providing an insight into the mechanisms of
      anti-tumor protection induced by tum- cells, these data offer useful information
      for the design of vaccination strategies against identified tumor antigens.

PMID- 7589073
TI  - Carrier-reactive hapten-specific cytotoxic T lymphocyte clones originate from a
      highly preselected T cell repertoire: implications for chemical-induced self
      reactivity.
AB  - We have recently described trinitrophenyl (TNP)-specific cytotoxic T lymphocyte
      (CTL) clones from C57BL/6 mice specific for hapten-modified peptides bearing a
      TNP-lysine in a peripheral position, i.e. in position 7 of H-2Kb-bound
      octapeptides. CTL recognition of such determinants is always sequence-dependent
      due to co-recognition of TNP as well as amino acid side chains of the carrier
      peptide. By the use of glycine-based designer peptides for primary induction of
      CTL in vitro, we have identified two sub-epitopes on individual position 7
      haptenated peptides that form two TcR contact points and which can be
      independently recognized by cloned CTL. One of these sub-epitopes is represented
      by the hapten itself, the other by the amino acids tyrosine and lysine in
      positions 3 and 4 of the carrier peptide, respectively. Immunization with such
      TNP-modified peptides frequently results in the specific induction of CTL also
      reacting with the unmodified carrier peptides. DNA sequence analyses of the TcR
      revealed an extraordinary similarity of several independent TcR of CTL from
      individual mice and induced with different TNP-peptides. These receptor
      similarities clearly correlate with structural elements common to the immunizing
      peptides and suggest their origin from positive thymic selection of TcR on Kb
      associated associated self-peptides bearing Tyr in position 3. Our data provide
      additional information concerning the topology of TcR binding to peptide/MHC
      complexes with, but also without, TNP. They also indicate a mechanism which might
      explain the potential of chemicals or drugs to induce autoimmune phenomena.

PMID- 7589075
TI  - Different forms of human vascular adhesion protein-1 (VAP-1) in blood vessels in
      vivo and in cultured endothelial cells: implications for lymphocyte-endothelial
      cell adhesion models.
AB  - Vascular endothelium plays a pivotal role in controlling leukocyte extravasation
      from the blood into the tissues. Vascular adhesion protein-1 (VAP-1) is a novel
      endothelial cell molecule which mediates lymphocyte binding to the vascular
      lining (Salmi, M., and Jalkanen, S., Science 1992. 257:1407). In this study, we
      analyzed endothelial cell type-specific differences of VAP-1. In vivo, VAP-1 is a
      90/170-kDa molecule which is mainly expressed on the lumenal surface and in
      cytoplasmic granules of peripheral lymph node-type postcapillary venules (high
      endothelial venules, HEV). In tonsil HEV, VAP-1 is modified with abundant sialic
      acids. VAP-1 is also detectable in the cytoplasm of human umbilical vein
      endothelial cells (HUVEC) and in an endothelial cell hybrid EaHy-926, although
      both cell types lack detectable surface VAP-1. Cultured endothelial cells do not
      express MECA-79-defined peripheral lymph node addressins either. VAP-1 was not
      translocated onto the endothelial cell surface after stimulation with multiple
      cytokines, mitogens or secretagogues which induced expression of other known
      endothelial adhesion molecules. Biochemical analyses revealed that VAP-1 is a
      approximately 180-kDa protein in these endothelial cell types. Digestions with
      neuraminidase, O-glycanase and N-glycanase, as well as treatment of cells with
      tunicamycin and benzyl-N-acetylgalactosaminide, did not alter the molecular mass
      of VAP-1 in EaHy-926. Pulse-chase experiments showed that VAP-1 is directly
      synthesized as a 180-kDa molecule without any detectable precursors. Thus, in
      cultured endothelial cells, VAP-1 is a 180-kDa protein which is devoid of post
      translational modifications, and in particular, lacks the sialic acids crucial
      for the function of VAP-1 in tonsil vessels. Notably, the endothelial cell types
      commonly used as a model in studying lymphocyte-endothelial cell interactions
      lack surface expression of VAP-1 and peripheral node addressins, and hence are
      inherently of limited use in analyses of the initial adhesion of lymphocytes.

PMID- 7589078
TI  - CD27/CD70 interaction directly drives B cell IgG and IgM synthesis.
AB  - CD27 is a T cell activation antigen expressed on a majority of peripheral blood T
      cells. CD27 is also expressed on a subpopulation of human B cells, and it is
      reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is
      expressed on activated T and B cells, suggesting an interaction between T and B
      cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis
      using a CD70 transfectant and present functional data showing that B cells
      secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A
      flow cytometric analysis showed that CD27 expression was increased and CD70 was
      expressed on tonsillar and peripheral blood B cells after activation with
      Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition,
      the proliferation of B cells was enhanced mildly by the addition of CD70
      transfectant, and its proliferation was blocked by anti-CD70 mAb. More
      importantly, the CD70 transfectant enhanced IgG and IgM production by purified B
      cells greatly in the presence of SAC plus IL-2. The enhancement was completely
      blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly
      suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays
      an important role in B cell growth and differentiation to produce IgG and IgM.

PMID- 7589077
TI  - Glucocorticoids down-regulate dendritic cell function in vitro and in vivo.
AB  - Exogenous glucocorticoid hormones are widely used as therapeutical agents,
      whereas endogenous glucocorticoids may act as physiological immunosuppressants
      involved in the control of immune and inflammatory responses. The optimal
      activation of T lymphocytes requires two distinct signals: the major
      histocompatibility complex-restricted presentation of the antigen and an
      additional co-stimulatory signal provided by the antigen-presenting cells. There
      is ample evidence that, among the cells able to present the antigen, the
      dendritic cells (DC) have the unique property to activate antigen-specific, naive
      T cells in vitro and in vivo, and are therefore required for the induction of
      primary immune responses. In this work, we tested whether glucocorticoids
      affected the capacity of DC to sensitize naive T cells. Our data show that, in
      vitro, the steroid hormone analog dexamethasone (Dex) affects the viability of
      DC, selectively down-regulates the expression of co-stimulatory molecules on
      viable DC, and strongly reduces their immunostimulatory properties. In vivo, a
      single injection of Dex results in impaired antigen presenting function, a
      finding which correlates with reduced numbers of splenic DC. These results show
      that glucocorticoids regulate DC maturation and immune function in vitro and in
      vivo and suggest that this mechanism may play a role in preventing
      overstimulation of the immune system.

PMID- 7589079
TI  - Altered CD40 ligand induction in tolerant T lymphocytes.
AB  - CD40 ligand (CD40L) is a member of the tumor necrosis factor superfamily and is
      expressed on the surface of activated T lymphocytes. The interaction of CD40L
      with CD40 on B cells results in B cell activation, immunoglobulin (Ig) secretion
      and Ig class switching. To study anergy as a mechanism of murine CD4 T cell
      tolerance, we determined both in vivo and in vitro that CD3-activated anergic
      cells are deficient in the ability to stimulate B cell proliferation, and that
      anergic cells are defective for the T cell receptor/CD3-mediated induction of
      CD40L expression. These results have implications for the recruitment of B cell
      responses by anergic T cells in vivo.

PMID- 7589076
TI  - T cells with dual antigen specificity in T cell receptor transgenic mice
      rejecting allografts.
AB  - Allelic exclusion of T cell receptor (TCR) genes is incomplete: a significant
      percentage (10-30%) of normal human and mouse peripheral T cells express two
      surface TCR alpha chains, and a small percentage of peripheral human T cells have
      been reported to express two surface TCR beta chains. A proportion of thymocytes
      in TCR transgenic mice rearrange endogenous T cell receptor genes, and peripheral
      T cells with two TCR alpha chains, transgenic and endogenous, have been reported.
      T cell clones with more than a single TCR heterodimer on their surface might be
      expected to show specificity for more than one cognate antigen: we report here a
      T cell clone with dual antigen specificity, isolated from an F5 TCR influenza
      nucleoprotein (NP 366-374/Db)-specific transgenic female mouse which had rejected
      an H-2-matched male skin graft. It was selected in vitro by stimulation with male
      H-2b spleen cells in the absence of the NP366-374 peptide but has specificity for
      both H-Y/Db and NP366-374. This contrasted with the single NP366-374/Db
      specificity shown by a control clone isolated from a Rag1-/- F5 mouse. The dual
      antigen specificity was associated with the rearrangement of endogenous TCR genes
      and cell surface expression of these as well as the TCR transgene.

PMID- 7589080
TI  - Induction of Th1 and Th2 CD4+ T cell responses by oral or parenteral immunization
      with ISCOMS.
AB  - We examined the ability of oral or parenteral immunization with immune
      stimulating complexes containing ovalbumin (ISCOMS-OVA) to prime T cell
      proliferative and cytokine responses. A single subcutaneous immunization with
      ISCOMS-OVA primed potent antigen-specific proliferative responses in the draining
      popliteal lymph node, which were entirely dependent on the presence of CD4+ T
      cells. CD8+ T cells did not proliferate in vitro even in the presence of the
      appropriate peptide epitope and exogenous interleukin (IL)-2. Primed popliteal
      lymph node cells produced IL-2, IL-5 and interferon (IFN)-gamma, but not IL-4
      when restimulated with OVA in vitro. Serum antigen-specific IgG1 and IgG2a
      antibody responses were also primed by subcutaneous immunization with ISCOMS-OVA,
      confirming the stimulation of both Th1 and Th2 cells in vivo. Spleen cells from
      subcutaneously primed mice produced a similar pattern of cytokines, indicating
      that disseminated priming had occurred. Oral immunization with ISCOMS-OVA also
      primed local antigen-specific proliferative responses in the mesenteric lymph
      node and primed an identical pattern of systemic cytokine responses in the
      spleen. The ability of ISCOMS to prime both Th1 and Th2 CD4+ T cell responses may
      be central to their potent adjuvant activities and confirm the potential of
      ISCOMS as future oral vaccine vectors.

PMID- 7589081
TI  - Differential binding of human interleukin-1 (IL-1) receptor antagonist to natural
      and recombinant soluble and cellular IL-1 type I receptors.
AB  - A recently described factor, interleukin-1 receptor antagonist binding factor (IL
      1raBF), in serum of normal individuals is immunologically related to the
      interleukin-1 receptor type I (IL-1RI). It is presumably a soluble form of the
      receptor that binds exclusively to interleukin-1 receptor antagonist (IL-1ra).
      Recombinant soluble human IL-1RI expressed in COS cells (sIL-1RI) consists of the
      extracellular part of the receptor and binds all three known IL-1 species but
      preferentially to Il-1ra. We further characterized the sizes and binding of IL
      1raBF and sIL-1RI to IL-1ra by polyacrylamide gel electrophoresis in the presence
      of sodium dodecylsulfate, ligand binding interference analyses, N-glycosidase
      treatment, concanavalin A affinity chromatography, and with the use of monoclonal
      antibodies (mAb) to human recombinant IL-1ra. We also evaluated the binding of IL
      1ra to cellular IL-1RI on MRC5 fibroblasts and the interference afforded by the
      soluble receptors. The results show that the protein backbones of IL-1raBF and
      sIL-1RI are of similar size (approximately 35-40 kDa) and that there are
      differences in the glycosylation of the two molecules. These carbohydrates were
      necessary for optimal binding of both molecules to IL-1ra. Both factors blocked
      binding of IL-1ra to cellular IL-1RI, as did mAb to IL-1ra, but the sites on IL
      1ra which bound to the mAb, and to IL-1raBF and sIL-1RI, differed. We conclude
      that there are important differences between the natural and recombinant forms of
      soluble IL-1RI and that IL-1ra binds differently to these molecules and to
      cellular IL-1RI.

PMID- 7589082
TI  - Induction of diabetes in standard mice by immunization with the p277 peptide of a
      60-kDa heat shock protein.
AB  - We previously reported that immunity to the p277 peptide of the human 60-kDa heat
      shock protein (hsp60) was a causal factor in the diabetes of non-obese diabetic
      (NOD) mice, which are genetically prone to develop spontaneous autoimmune
      diabetes. The present study was done to test whether immunization with the p277
      peptide could cause diabetes in standard strains of mice. We now report that a
      single administration of the p277 peptide conjugated to carrier molecules such as
      bovine serum albumin or ovalbumin can induce diabetes in C57BL/6 mice and in
      other strains not genetically prone to develop diabetes. The diabetes was marked
      by hyperglycemia, insulitis, insulin autoantibodies, glucose intolerance and low
      blood levels of insulin. The diabetes could be transferred to naive recipients by
      anti-p277 T cell lines. Similar to other experimentally induced autoimmune
      diseases, the autoimmune diabetes remitted spontaneously. After recovery, the
      mice were found to have acquired resistance to a second induction of diabetes.
      Susceptibility to induced diabetes in C57BL/6 mice was influenced by sex (males
      were much more susceptible than were females) and by class II genes in the major
      histocompatibility complex (B6.H-2bm12 mice with a mutation in the MHC-II
      molecule were relatively resistant). Other strains of mice susceptible to induced
      diabetes were C57BL/KSJ, C3HeB/FeJ, and NON/Lt. BALB/c and C3H/HeJ strains were
      relatively resistant. Immunization to p277-carrier conjugates could also induce
      transient hyperglycemia in young NOD mice, but upon recovery from the induced
      diabetes, the NOD mice were found to have acquired resistance to later
      development of spontaneous diabetes. Thus, T cell immunity to the p277 peptide
      can suffice to induce diabetes in standard mice, and a short bout of induced
      diabetes can affect the chronic process that would otherwise lead to spontaneous
      diabetes in diabetes-prone NOD mice.

PMID- 7589083
TI  - Low-dose UVB radiation perturbs the functional expression of B7.1 and B7.2 co
      stimulatory molecules on human Langerhans cells.
AB  - In previous studies, we have shown that ultraviolet (UV) B radiation perturbs the
      APC function of Langerhans cells (LC) by interfering with as-yet unidentified co
      stimulatory signals. Recently, B7.1 and B7.2 on APC were shown to deliver
      important co-stimulatory signals through interaction with their counter receptors
      CD28 and CTLA-4 on T cells. To determine whether UVB affects the functional
      expression of B7.1 or B7.2 on LC, B7.1 and B7.2 expression was studied on human
      LC by multiparameter flow cytometry. Little, if any, B7.1 or B7.2 was detected on
      LC freshly isolated from skin. However, following 48 h of tissue culture,
      expression of both B7.1 and B7.2 were markedly up-regulated. To test whether
      these molecules were functional, primary mixed epidermal cell leukocyte reactions
      (MECLR) were performed. Blocking monoclonal antibody (mAb) to B7.1 or B7.2 both
      inhibited the MECLR, with anti-B7.2 being much more effective than anti-B7.1. UVB
      radiation dose-dependently (100-200 J/m2) suppressed the culture-induced up
      regulation of B7.1 and B7.2 on LC. Since LC exposed to the same UVB flux (UVB-LC)
      failed to stimulate alloreactive T cells in a MECLR, we questioned whether this
      was related to their inability to provide B7 co-stimulation. Indeed, when
      effective B7-CD28 signaling was ascertained by adding submitogenic doses of
      exogenous anti-CD28 mAb to UVB-LC, the proliferative response of alloreactive T
      cells was restored. We conclude that the suppressive effects of low-dose UVB
      radiation on the APC function of LC are, at least in part, due to an inhibition
      of functional B7.1 and B7.2 expression.

PMID- 7589084
TI  - The role of tyrosine phosphorylation in the interaction of cellular tyrosine
      kinases with the T cell receptor zeta chain tyrosine-based activation motif.
AB  - Immunoglobulin receptor family tyrosine-based activation motifs (ITAM) define a
      conserved signaling sequence, EX2YX2L/IX7YX2L/I, that mediates coupling of the T
      cell antigen receptor (TCR) to protein tyrosine kinases (PTK). In the present
      study, we explored the role of phosphorylation of the two ITAM tyrosine residues
      in the interactions of the motif with the PTK ZAP-70 and p59fyn. The data show
      that the phosphorylation of a single tyrosine within the motif enables binding of
      p59fyn, whereas phosphorylation of both tyrosines within the motif is required
      for maximal binding of the PTK ZAP-70. Quantitative binding experiments show that
      nanomolar concentrations of the doubly phosphorylated zeta 1-ITAM are sufficient
      for ZAP-70 recruitment, whereas micromolar levels of singly phosphorylated ITAM
      are necessary for p59fyn binding. ZAP-70 binds with low efficiency to a singly
      phosphorylated ITAM, but shows preferential binding to the C-terminal
      phosphotyrosine in the ITAM, whereas p59fyn binds selectively to the N-terminal
      phosphotyrosine. The present data thus show that there is the potential for a
      singly phosphorylated ITAM to couple to cellular PTK. Moreover, the data suggest
      a mechanism for heterogeneity in signal transduction responses by the TCR, since
      ITAM could differentially couple the TCR to downstream signaling events depending
      on their phosphorylation state.

PMID- 7589085
TI  - CD30 ligation induces nuclear factor-kappa B activation in human T cell lines.
AB  - CD30 is a recently described member of the tumor necrosis factor/nerve growth
      factor receptor superfamily. In this report, we show that following incubation of
      L540 cells (Hodgkin's disease-derived, T cell-like, CD30+ cells) with the
      agonistic anti-CD30 monoclonal antibodies (mAb) M44 and M67, two nuclear factor
      (NF)-kappa B DNA binding activities were induced in nuclear extracts, as
      determined in gel retardation assays. The effect of the mAb towards NF-kappa B
      activation was rapid, as it occurred within 20 min, and was sustained for up to 6
      h. By comparison, an isotype-matched antibody had no effect on NF-kappa B
      activation. Moreover, in human T helper (Th) clones functionally characterized as
      being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively),
      the extent of CD30-mediated NF-kappa B activation correlated with the proportion
      of CD30+ cells. In all cell lines investigated, the NF-kappa B complexes induced
      following CD30 engagement were shown to contain p50 NF-kappa B1, p65 RelA, and
      possibly other transcription factors. Collectively, our results demonstrate that
      nuclear translocation and activation of NF-kappa B rank among the short-term
      cellular responses elicited following CD30 ligation.

PMID- 7589086
TI  - Protective role of gamma/delta T cells and alpha/beta T cells in tuberculosis.
AB  - Tuberculosis is a chronic infectious disease which causes major health problems
      globally. Although acquired resistance crucially depends on alpha/beta
      lymphocytes, circumstantial evidence suggests that, in addition, gamma/delta T
      lymphocytes contribute to protection against tuberculosis. We have studied
      Mycobacterium tuberculosis infection in TcR-delta-/- or TcR-beta-/- gene deletion
      mutants which completely lack gamma/delta T cells or alpha/beta T cells,
      respectively. Low inocula of M. tuberculosis led to death of TcR-beta-/- mice and
      transient disease exacerbation in TcR-delta-/- mutants. Infection with higher
      inocula caused rapid death of TcR-delta-/- mice. The development of and bacterial
      containment in granulomatous lesions was markedly impaired in TcR-beta-/-, and
      less severely affected in TcR-delta-/- mutants. Mycobacteria-induced IFN-gamma
      production by spleen cells in vitro was almost abolished in TcR-beta-/- and
      virtually unaffected in TcR-delta-/- mice. Our data confirm the crucial role of
      alpha/beta T cells in protection against established tuberculosis and formally
      prove a protective role of gamma/delta T cells in early tuberculosis.

PMID- 7589087
TI  - Enhancement of endotoxin-induced interleukin-10 production by SR 31747A, a sigma
      ligand.
AB  - SR 31747A is a new sigma ligand eliciting immunosuppressive and anti-inflammatory
      properties. Here, we show that SR 31747A greatly enhances lipopolysaccharide
      (LPS)-induced systemic release of interleukin (IL)-10, while it inhibits the
      secretion of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. In
      line with this finding, we also show by using quantitative reverse transcription
      polymerase chain reaction analysis that SR 31747A increased LPS-induced IL-10
      mRNA accumulation in spleen cells, whereas the level of both TNF-alpha and IFN
      gamma mRNA was dramatically decreased. The enhancement of IL-10 production by SR
      31747A treatment was also apparent in nude and severe-combined immunodeficient
      mice treated with LPS, clearly indicating that T and B cells were not involved.
      Finally, SR 31747A conferred protection against the lethal effect of LPS. The
      finding that SR 31747A strongly stimulates the synthesis of the natural anti
      inflammatory cytokine IL-10, a property not observed with dexamethasone, provides
      new insights for the clinical use of this original compound, particularly in
      chronic inflammatory diseases where IL-10 is believed to be a pivotal regulatory
      component.

PMID- 7589088
TI  - Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor
      necrosis factor-alpha.
AB  - Interleukin (IL)-10 is known to protect mice against the lethal effects of
      lipopolysaccharides (LPS) and is considered to be an anti-inflammatory cytokine
      which suppresses the production of pro-inflammatory cytokines. We have examined
      the interactions of the pro-inflammatory cytokine tumor necrosis factor-alpha
      (TNF-alpha) with IL-10. Neutralization of TNF-alpha in murine bone marrow-derived
      macrophages resulted in a significant reduction of LPS-inducible IL-10
      production. In mice, injection of 5 mg/kg LPS induced circulating IL-10 with a
      biphasic time course exhibiting an early peak 1.5 h after challenge (synchronous
      with TNF-alpha) and, after a nadir at 6 h, a second increase between 8 and 12 h.
      Treatment of mice with neutralizing anti-mouse TNF-alpha antiserum significantly
      increased LPS-induced IL-10 plasma levels between 1.5 and 6 h but diminished
      those at 12 h, while circulating IL-6, interferon-gamma (IFN-gamma) and
      granulocyte colony-stimulating factor (G-CSF) concentrations were attenuated
      overall, without a biphasic response. Analysis of LPS-induced IL-10 mRNA
      expression in different tissues 1 h and 8 h after LPS or LPS plus anti-TNF-alpha
      revealed that the amount of transcripts in the liver correlated with circulating
      early and late IL-10 levels. Our findings suggest that endogenous TNF-alpha down
      regulates the early and up-regulates the late LPS-induced IL-10 synthesis in vivo
      and that the liver is the major source of circulating IL-10 after stimulation
      with LPS.

PMID- 7589089
TI  - Major histocompatibility complex class II-associated peptides determine the
      binding of the superantigen toxic shock syndrome toxin-1.
AB  - Superantigens bind to major histocompatibility complex (MHC) class II proteins
      and interact with variable parts of the T cell antigen receptor (TCR) beta-chain.
      Cross-linking the TCR with MHC class II molecules on the antigen-presenting cell
      by the superantigen leads to T cell activation that plays an essential role in
      pathogenesis. Recent crystallographic data have resolved the structure of the
      complexes between HLA-DR1 and staphylococcal enterotoxin B (SEB) and toxic shock
      syndrome toxin-1 (TSST-1), respectively. For TSST-1, these studies have revealed
      possible contact sites between the superantigen and the HLA-DR1-bound peptide.
      Here, we show that TSST-1 binding is dependent on the MHC-II-associated peptides
      by employing variants of T2 mutant cells deficient in loading of peptides to MHC
      class II molecules as superantigen-presenting cells. On HLA-DR3-transfected T2
      cells, presentation of TSST-1, but not SEB, was dependent on HLA-DR3-associated
      peptides. Thus, although these superantigens can be recognized in the context of
      multiple MHC class II alleles and isotypes, they clearly bind to specific subsets
      of MHC molecules displaying appropriate peptides.

PMID- 7589090
TI  - Oxpentifylline inhibits tumor necrosis factor-alpha mRNA transcription and
      protects against arthritis in mercuric chloride-treated brown Norway rats.
AB  - The phosphodiesterase inhibitor oxpentifylline (OXP) has a number of potentially
      important immunomodulatory actions which include a selective inhibition of the
      Th1 subset of CD4+ cells in vitro and inhibition of tumor necrosis factor (TNF)
      alpha mRNA transcription. In vivo, it has a dramatic protective effect against
      experimental allergic encephalomyelitis. In this animal model, tissue injury is
      associated with both a Th1 response and with TNF-alpha production, either of
      which could be targets for the protective action of OXP. In an attempt to clarify
      the relative importance of the Th cell subsets and TNF-alpha in pathogenesis, we
      investigated the effect of OXP on a Th2 model of T cell-dependent disease,
      mercuric chloride (HgCl2)-induced autoimmunity in the Brown Norway rat. The
      effects of OXP on the Th1:Th2 response, TNF-alpha mRNA transcription in spleen
      and ankle joints, and on the incidence and severity of arthritis and cecal
      vasculitis have been examined and the effects in vivo have been compared with
      those of a soluble TNF receptor-IgG1 fusion protein (sTNFR) that neutralizes rat
      TNF-alpha. In two separate experiments, OXP significantly enhanced unstimulated
      levels of splenic interleukin-4 (IL-4) mRNA (median 62%, of an artificial IL-4
      mRNA construct, vs. 36.5% in controls) and in one experiment, exaggerated the
      total IgE response to HgCl2. OXP inhibited HgCl2-induced TNF-alpha mRNA
      transcription in spleen and ankle joints. In three separate experiments, OXP had
      a significant protective effect against arthritis, with the mean incidence
      reduced from 100% to 30% and mean peak score reduced from 7.2 to 2.59
      (experiments 1 and 2). The protection against arthritis was indistinguishable
      from that produced by sTNFR. There was no such protection against cecal
      vasculitis with either OXP or sTNFR. These results demonstrate that OXP induces a
      shift towards a Th2 response, inhibits TNF-alpha mRNA transcription locally in
      joint and systemically in spleen, and has a protective effect against arthritis
      similar to that produced by sTNFR in the HgCl2-treated BN rat. We conclude that
      TNF-alpha is a critical cytokine in the pathogenesis of arthritis but not cecal
      vasculitis in this model, and that inhibition of TNF-alpha transcription is the
      most important mode of action of OXP in this situation. OXP may be a potential
      therapeutic agent in the treatment of other arthritides, such as human rheumatoid
      arthritis, in which TNF-alpha has been implicated in pathogenesis.

PMID- 7589092
TI  - Ligation of either CD2 or CD28 rescues CD4+ T cells from HIV-gp120-induced
      apoptosis.
AB  - Temporal or quantitative imbalance in signals delivered to T cells via T cell
      antigen receptor (TCR), the CD4 co-receptor, and accessory molecules can lead to
      anergy, apoptosis, or both. This has been observed following ligation of CD4 by
      HIV gp120 prior to TCR occupancy. The ability of molecules such as CD2 and CD28,
      interacting with their ligands LFA-3 and B7, to provide signals that protect T
      cells from the induction of anergy, has been reported. Here, we demonstrate that
      ligation of CD2 and CD28 in conjunction with TCR occupancy rescue T cells that
      have been programmed for apoptotic death by prior CD4 ligation to gp120. This
      appears to be the result of augmented interleukin-2 and interleukin-4 release by
      the T cells following these molecular interactions. In conclusion, our results
      suggest that an impairment of antigen-presenting accessory cell functions could
      favor gp120-mediated apoptosis in HIV-uninfected cells.

PMID- 7589091
TI  - Differential susceptibility to monomeric HIV gp120-mediated apoptosis in antigen
      activated CD4+ T cell populations.
AB  - To support the hypothesis that indirect mechanisms mediated by viral products
      like the HIV envelope glycoprotein gp120 could be responsible for T lymphocyte
      depletion in HIV infection, we developed a system in which the impairment of T
      cell functions could be investigated in vitro. In particular, we characterized
      the conditions that allow T lymphocytes repeatedly stimulated with an antigen to
      be sensitive or resistant to gp120-mediated apoptotic signals. To achieve this
      goal, a panel of antigen-specific CD4+ T cell clones and primary CD4+ T
      lymphocytes were treated for 2 and 18 h with saturating amounts of monomeric
      gp120 (without cross-linking with specific antibodies) and antigen-driven T cell
      proliferation and apoptosis were analyzed. We show that monomeric gp120 induces
      apoptosis only in T lymphocytes repeatedly stimulated with the antigen, that
      primary T lymphocytes are resistant to programmed cell death mediated by
      monomeric gp120, but are sensitive to anti-CD4 antibodies, and that gp120
      mediated apoptosis is dependent on the period of time between the binding of
      gp120 to CD4 and the encounter with antigen. To investigate the different
      susceptibility to gp120 induced apoptosis of primary CD4+ and T cell clones
      further, the number of membrane CD4 molecules and their affinity for gp120,
      together with Bcl-2 and Fas expression, were studied. Our data suggest that a
      down-modulation of membrane CD4 together with high expression of the Bcl-2 gene
      and protein characterizes the susceptibility to apoptosis of gp120-treated cells.
      In conclusion, our results define the phenotypic features of T cells susceptible
      to HIV gp120-induced apoptosis and demonstrate that the same clonotype, depending
      on the activation state, may present a differential sensitivity to apoptosis
      induction.

PMID- 7589093
TI  - NKG2-C is a receptor on human natural killer cells that recognizes structures on
      K562 target cells.
AB  - NKG2-C is a member of the recently discovered NKG2 family of genes and proteins,
      which are preferentially expressed on human natural killer (NK) cells. These
      potential NK cell receptors belong to a larger class of type II transmembrane
      proteins with a C-type lectin domain. We show here that NKG2-C is expressed as a
      36-kDa glycoprotein by translation in vitro, recombinant expression and
      immunoprecipitation from a human NK cell clone. Further, a recombinant soluble
      NKG2-C-receptor binds specifically to K562 cells, which are target cells for NK
      cell killing, and to RPMI 8866 cells, which are feeder cells for NK cells;
      several other hematopoietic cell lines tested do not show any binding. The
      binding structures on the surface of K562 cells disappear, concomitant with a
      loss in susceptibility to killing when the cells are induced to differentiate
      with phorbol ester and Ca2+ ionophore. Our data suggest the presence of specific
      target molecules for NKG2-C on K562 cells, since overall glycosylation, Lewis X
      and Lewis Y structures, as well as the mucin-like CD43 molecule, do not change
      following induction of the cells. We propose that NKG2-C mediates a specific
      interaction of NK cells and their target cells with functional importance for NK
      cell killing.

PMID- 7589096
TI  - Characterization of Fc gamma receptors on rat mucosal mast cells using a mutant
      Fc epsilon RI-deficient rat basophilic leukemia line.
AB  - A novel rat basophilic leukemia (RBL) 2H3 subline of rat mucosal mast cells
      deficient in the expression of the gamma chain (RBL-gamma-) has permitted
      functional characterization of their low-affinity Fc gamma receptors (Fc gamma
      R). A rat Fc gamma RII analog of the mouse b2 isoform has been earlier identified
      and its transcript detected in RBL-2H3 cells. We have noew isolated and sequenced
      the rat Fc gamma RIIb1 isoform and observed differences between its expression in
      RBL-2H3 and RBL-gamma-. Furthermore, we demonstrate that rat mucosal mast cells
      express a second, low-affinity Fc gamma receptor, namely the Fc gamma RIII.
      Stimulation of either cell line with IgG complexes decreased the expression of
      transcripts for all Fc gamma R. Hence, ligation of Fc gamma R on rat mucosal mast
      cells apparently regulate their transcription. Selective stimulation through the
      Fc gamma RII or Fc gamma RII/III systems, respectively, was accomplished by
      either using RBL-gamma- line or by saturating the Fc epsilon RI on RBL-2H3 with
      monomeric IgE. RBL-gamma-cells, which do carry Fc gamma RII (but lack Fc epsilon
      RI and Fc gamma RIII), do not respond to IgG (and IgE) immune complexes as
      monitored by specific protein tyrosine phosphorylation, degranulation or cytokine
      secretion. This finding, together with the restoration of the functional
      phenotype of parental cells upon gamma chain cDNA transfection into RBL-gamma-
      cells, unequivocally excludes the possible stimulation of rat mucosal mast cells
      by clustering of their Fc gamma RII. Fc epsilon RI saturation by IgE on parental
      RBL-2H3 cells completely blocks their response to IgG immune complexes. Thus the
      Fc gamma R on these cells do not trigger degranulation and this is not due to the
      absence of Fc gamma RIII as previously suggested. Therefore, co-clustering of Fc
      gamma RII and Fc gamma RIII on rat mucosal mast cells does not seem to stimulate
      them. A possible inhibitory role of Fc gamma RII in this process is suggested and
      discussed.

PMID- 7589094
TI  - Involvement of CD44 variant isoforms in hyaluronate adhesion by human activated T
      cells.
AB  - The standard, 85-95-kDa form of the hyaluronic acid (HA) receptor CD44 and a
      number of CD44 mRNA splice variants play important roles in immune responses and
      tumor metastasis. Variants carrying exon 6 (v6), or 9 (v9) products are
      transiently expressed on activated human T cells. Here, modulation experiments
      with specific monoclonal antibodies (mAb) indicate that v6 and v9 are expressed
      independently on distinct sets of CD44 molecules, and that their combined
      expression is necessary for HA adhesion. Moreover, the finding that mAb-mediated
      cross-linking of v6 and v9 promoted cytosolic free Ca2+ mobilization and co
      stimulated CD3-triggered T cell proliferation indicates that v6 and v9 possess
      signaling and effector function activation ability. Finally, HA-mediated
      signaling appears to be required for variant-dependent adhesion to HA. The
      observation that soluble HA promoted cytosolic free Ca2+ mobilization indicates
      that HA-induced Ca2+ mobilization can occur during T cell-HA interaction. Since
      Ca2+ mobilization was inhibited by pretreatment of cells with an anti-CD44 mAb
      directed against the HA-binding domain of CD44, CD44 receptors appear to be
      involved in HA-mediated signal transduction. The requirement of cytosolic free
      Ca2+ for adhesion is shown by the fact that ionomycin (a Ca2+ ionophore)
      stimulated, and EGTA (a Ca2+ chelator), inhibited HA adhesion. In addition,
      cytoskeletal functional activation is required for cell adhesion to HA, since
      drugs that block actin polymerization, such as cytochalasin B, or actomyosin
      contraction, such as the calmodulin antagonist W-7, inhibited cell adhesion to
      HA. As this adhesion is also ADP ribosylation-sensitive, it may involve a GTP
      dependent function of CD44v, i.e. ankyrin binding. Our data indicate that there
      is a functional hierarchy among the CD44 molecules expressed on human peripheral
      blood T cells and that the splice variants, as compared to the standard form,
      exhibit a greater HA binding ability which involves CD44-mediated signaling and
      effector function activation.

PMID- 7589097
TI  - Interleukin-7 activates p56lck and p59fyn, two tyrosine kinases associated with
      the p90 interleukin-7 receptor in primary human T cells.
AB  - We have investigated signaling events associated with the cloned 90-kDa (p90)
      interleukin-7 receptor (IL-7R) to determine whether changes in the signaling
      pathways initiated by this molecule can explain the ability of T cells to
      proliferate to IL-7 following activation. Using in vitro kinase assays we find
      that the p90 IL-7R in both unstimulated and activated human T cells is physically
      associated with two molecules with intrinsic kinase activity. Western blotting
      analysis reveals these proteins to be the src kinase enzymes, p59fyn and p56lck.
      Binding of human recombinant IL-7 to the p90 IL-7R results in increased activity
      of both receptor-associated kinases in both resting and activated mature T cells.
      Thus, the signaling pathways initiated via the p90 IL-7R-associated src kinases
      are unlikely to be solely responsible for the proliferation of only activated T
      cells in response to IL-7. Additional signals, which may derive from other IL-7R
      associated molecules such as the gamma c, are clearly required for IL-7-driven
      proliferation of activated primary T cells.

PMID- 7589095
TI  - Expression and function of the murine CD95/FasR/APO-1 receptor in relation to B
      cell ontogeny.
AB  - Mice defective in Fas-mediated apoptosis (lpr phenotype) have an intrinsic B cell
      abnormality that predisposes them to autoantibody production. To investigate
      potential roles for the Fas receptor (FasR) in B cell tolerance, FasR expression
      and function were evaluated at different stages of B cell development. FasR
      expression was very low or absent on pro- and pre-B cells, but was detected in
      early B cell lines and was up-regulated following IFN-gamma-induced maturation of
      the pre-B cell line 70-Z. Whereas FasR expression was very low in resting mature
      sIgM+ B cells, expression was markedly increased following mitogen activation and
      was also elevated in two mature sIgG+ lymphoma lines. FasR expression correlated
      strongly with the ability of B cells to undergo Fas-mediated apoptosis. In
      addition, although Fas did not appear to play a direct role in apoptosis mediated
      by cross-linking of sIg with anti-IgM, anti-FasR and sublethal concentrations of
      anti-Ig were additive in the induction of apoptosis in the early B cell line WEHI
      231. These findings suggest that the Fas pathway is not involved in the
      elimination of pro- and pre-B cells, but are compatible with an ancillary role
      for FasR in the elimination of early B cells and elimination of mature B cells
      following activation.

PMID- 7589098
TI  - Interleukin-4 inhibits kappa light chain expression and NF kappa B activation but
      not I kappa B alpha degradation in 70Z/3 murine pre-B cells.
AB  - The murine pre-B cell line 70Z/3 responds to lipopolysaccharide by up-regulating
      the surface expression of kappa (kappa) light chain through activation of the
      transcription factor NF kappa B. Interleukin-4 (IL-4), a T cell cytokine, is a
      known inhibitor of some LPS-mediated events. We investigated whether IL-4 could
      inhibit the up-regulation of kappa light chain and activation of NF kappa B by
      LPS in 70Z/3. IL-4 partially inhibited both the LPS-induced expression of kappa
      light chain and also the activation of NF kappa B as judged by an NF kappa B
      reporter gene assay. Additionally, electrophoretic mobility shift assays
      confirmed this effect on LPS-induced NF kappa B DNA binding activity in the
      nucleus. Surprisingly, proteolytic degradation of I kappa B alpha (MAD3), a
      prerequisite for NF kappa B activation, was unaffected by IL-4, implying that
      this cytokine inhibits some subsequent undefined event in the activation of NF
      kappa B. IL-4 was also found partially to inhibit NF kappa B activity induced by
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta). These
      results indicate that there may be a common mechanism for the well-documented
      anti-inflammatory effects of IL-4 and that this mechanism involves the
      transcription factor NF kappa B.

PMID- 7589099
TI  - Listeriolysin generates a route for the presentation of exogenous antigens by
      major histocompatibility complex class I.
AB  - We have exploited the pore forming activity of listeriolysin, the hemolysin of
      Listeria monocytogenes, to activate CD8+ T cells with soluble proteins in vivo
      and in vitro. Immunization with soluble, hemolytically active listeriolysin
      induces both cytotoxic CD8+ T cells and CD4+ T cells, and the CD8+ T cells can be
      propagated with soluble listeriolysin in vitro. Moreover, conventional antigens
      like ovalbumin mixed together with listeriolysin are also efficiently introduced
      into the MHC class I pathway in vitro and in vivo. Hence, listeriolysin
      effectively directs itself and passenger molecules into the intracellular
      compartment that leads to the cytotoxic T cell response. In this way, we
      circumvent the bias of CD8+ T cells to recognize intracellular antigens presented
      by major histocompatibility complex class I molecules. As cytotoxic CD8+ T cells
      are of pivotal importance in eliminating viral and microbial pathogens, the
      findings reported here could prove to be useful in vaccine development.

PMID- 7589100
TI  - CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation.
AB  - A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule
      that plays a key role in T cell-dependent B cell stimulation. CD8+ T cell clones
      were examined for CD40L expression and for their capacity to allow the growth and
      differentiation of B cells, upon activation with immobilized anti-CD3. According
      to CD40L expression, CD8+ clones could be grouped into three subsets. CD8+ T cell
      clones expressing high levels of CD40L (> or = 80% CD40L+ cells) were equivalent
      to CD4+ T cell clones with regard to induction of tonsil B cell proliferation and
      immunoglobulin (Ig) production, provided the combination of interleukin (IL)-2
      and IL-10 was added to cultures. CD8+ T cell clones, with intermediate levels of
      CD40L expression (10 to 30% CD40L+ cells), also stimulated B cell proliferation
      and Ig secretion with IL-2 and IL-10. B cell responses induced by these CD8+ T
      cell clones were neutralized by blocking monoclonal antibodies specific for
      either CD40L or CD40. By contrast, CD40L- T cell clones (< or = 5% CD40L+ cells),
      only induced marginal B cell responses even with IL-2 and IL-10. All three clone
      types were able to activate B cells as shown by up-regulation of CD25, CD80 and
      CD86 expression. A neutralizing anti-CD40L antibody indicated that T cell
      dependent B cell activation was only partly dependent on CD40-CD40L interaction.
      These CD40L- clones had no inhibitory effects on B cell proliferation induced by
      CD40L-expressing CD8+ T cell clones. Taken together, these results indicate that
      CD8+ T cells can induce B cell growth and differentiation in a CD40L-CD40
      dependent fashion.

PMID- 7589101
TI  - Specific binding of Fyn and phosphatidylinositol 3-kinase to the B cell surface
      glycoprotein CD19 through their src homology 2 domains.
AB  - CD19 is a B cell surface protein capable of forming non-covalent molecular
      complexes with a number of other B cell surface proteins including the
      CD21/CD81/Leu-13 complex as well as with surface immunoglobulin. CD19 tyrosine
      phosphorylation increases after B cell activation, and is proposed to play a role
      in signal transduction through its cytoplasmic domain, which contains nine
      tyrosine residues. Several second messenger proteins have been shown to
      immunoprecipitate with CD19, including p59 Fyn (Fyn), p59 Lyn (Lyn) and
      phosphatidylinositol-3 kinase (PI-3 kinase). These associations are predicted to
      occur via the src-homology 2 (SH2) domains of the second messenger proteins. Two
      of the cytoplasmic tyrosines in the CD19 cytoplasmic region contain the consensus
      binding sequence for the PI-3 kinase SH2 domain (YPO4-X-X-M). However, the
      reported consensus binding sequence for the Fyn and Lyn SH2 domains (YPO4-X-X
      I/L) is not found in CD19. We investigated the capacity of CD19 cytoplasmic
      tyrosines to bind both Fyn and PI-3 kinase SH2-domain fusion proteins. In
      activated B cells, both Fyn and PI-3 kinase SH2-domain fusion proteins
      precipitate CD19. Using synthetic tyrosine-phosphorylated peptides comprising
      each of the CD19 cytoplasmic tyrosines and surrounding amino acids, we
      investigated the ability of the Fyn SH2 and PI-3 kinase SH2 fusion proteins to
      bind to the different CD19 cytoplasmic phosphotyrosine peptides. ELISA revealed
      that the two CD19 cytoplasmic tyrosine residues contained within the Y-X-X-M
      sequences (Y484 and Y515) bound preferentially to the PI-3 kinase SH2-domain
      fusion proteins. Two different tyrosines (Y405 and Y445) bound preferentially to
      the Fyn SH2-domain fusion protein via a novel sequence, Y-E-N-D/E, different from
      that previously reported for the Fyn SH2 domain. In precipitation studies,
      peptide Y484 was able to compete with tyrosine phosphorylated CD19 specifically
      for binding to the PI-3 kinase SH2 domain fusion proteins, while peptides Y405
      and Y445 were able to compete specifically for binding to the Fyn SH2 domain
      fusion proteins. These results indicate that CD19 may be capable of binding both
      Fyn and PI-3 kinase concurrently, suggesting a mechanism for CD19 signal
      transduction, in which binding of PI-3 kinase to the Fyn SH3 domain results in
      activation of PI-3 kinase.

PMID- 7589103
TI  - Interleukin-10 inhibits IgE-mediated nitric oxide synthase induction and cytokine
      synthesis in normal human keratinocytes.
AB  - Human keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators
      following activation with either IgE/anti-IgE immune complexes or a combination
      of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Recently,
      interleukin-10 (IL-10) has been shown to down-regulate various inflammatory
      responses and to be secreted by lymphocytes and dendritic cells during skin
      inflammatory reactions. We show here that IL-10 down-regulates the production of
      tumor necrosis factor (TNF)-alpha and IL-6 by activated HK. Also, induction of
      inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti-IgE or
      LPS/IFN-gamma is significantly reduced by the addition of IL-10. This effect is
      dose dependent and correlates with reduction of iNOS mRNA production and enzyme
      level. Therefore, IL-10 down-regulates NO-mediated HK inflammatory responses and
      may thus participate in the regulation of the skin immune network.

PMID- 7589102
TI  - Specific elimination of IgE production using T cell lines expressing chimeric T
      cell receptor genes.
AB  - B cells that are destined to secrete IgE express a membrane-bound form of IgE
      (mIgE) on their cell surface. Thus, elimination of such mIgE-positive cells
      should result in the suppression of IgE production, thereby alleviating the
      symptoms of IgE-mediated allergy. In this study, we examined, in a model system,
      whether IgE-specific effector T cells can be used specifically to eradicate IgE
      producing B cells. To this end, we endowed T cells with anti-IgE specificity
      using chimeric T cell receptors (cTCR) containing the variable region domain (Fv)
      of the 84.1c non-anaphylactic anti-mouse IgE monoclonal antibody (mAb). Two
      configurations of chimeric receptor were used: in the first, we combined the
      heavy and light variable region chains of 84.1c with the constant (C) regions of
      the TCR alpha and beta chains. The second construct consisted of a chimeric
      single-chain receptor (scFvR), composed of a single-chain Fv region of the 84.1c
      antibody and the C beta domain of the TCR. Following transfection of the cTCR or
      the scFvR genes into the murine MD.45 cytotoxic T cell hybridoma or the Jurkat
      human T cell line, functional expression of IgE-specific chimeric receptors was
      detected on the cell surface. The transfected cells secreted interleukin-2 upon
      stimulation with immobilized IgE or fixed IgE-producing hybridoma cells.
      Moreover, cytotoxic T cell hybridomas expressing the chimeric receptor genes
      specifically eliminated IgE-secreting B cells in vitro, resulting in isotype
      specific suppression of IgE production.

PMID- 7589106
TI  - Thy-1-mediated activation of rat basophilic leukemia cells does not require co
      expression of the high-affinity IgE receptor.
AB  - The glycosylphosphatidylinositol (GPI)-anchored protein Thy-1 is one of the most
      abundant molecules expressed on the surface of rat mast cells and rat basophilic
      leukemia cells, RBL-2H3. Antibody-mediated aggregation of Thy-1 induces in these
      cells release of secretory components; so does aggregation of the receptor with
      high affinity for IgE (Fc epsilon RI). To examine whether there is any
      relationship between Thy-1- and Fc epsilon RI-mediated activation, we have
      isolated from mutagenized RBL-2H3 cells a variant cell line deficient in the
      expression of surface Fc epsilon RI, and analyzed its ability to be activated by
      an antibody to Thy-1. Northern and immuno-blot analyses revealed that the variant
      cells were deficient in the expression of a structural or a regulatory gene for
      Fc epsilon RI gamma subunit. The cells did not respond by release of
      secretagogues and protein-tyrosine phosphorylation to IgE and antigen and anti-Fc
      epsilon RI monoclonal antibody (mAb) but their response to anti-Thy-1.1 mAb and
      calcium ionophore A23187 was retained. Transfection of the cloned Fc epsilon RI
      gamma subunit into the variant cells restored the surface expression of Fc
      epsilon RI and responsiveness to both the antigen and anti-Fc epsilon RI mAb but
      had no effect on responsiveness to anti-Thy-1 mAb. The combined data indicate
      that aggregation of surface Thy-1 glycoproteins activates a metabolic pathway
      which is independent of the presence of Fc epsilon RI gamma subunit and surface
      expression of Fc epsilon RI.

PMID- 7589105
TI  - Apoptotic death of lymphocytes in murine acquired immunodeficiency syndrome:
      involvement of Fas-Fas ligand interaction.
AB  - Murine acquired immunodeficiency syndrome (MAIDS) is caused by a defective murine
      leukemia virus. The disease is characterized by abnormal lymphoproliferation,
      impaired T and B cell function and aberrant regulation of cytokines. Both T and B
      lymphocytes show activated phenotypes, but undergo apoptotic death with
      characteristic DNA fragmentation. These results indicate the presence of a
      continuous activation death pathway of the lymphocytes in MAIDS. Overexpression
      of the bcl-2 transgene in lymphocytes showed no effect on the apoptotic cell
      death or on the development of the disease. In contrast, mice carrying mutations
      in either Fas or Fas ligand exhibited accelerated progression of the disease upon
      infection with MAIDS virus. These results suggest the involvement of Fas-Fas
      ligand system in the pathogenesis of MAIDS.

PMID- 7589104
TI  - Clonal deletion of major histocompatibility complex class I-restricted CD4+CD8+
      thymocytes in vitro is independent of the CD95 (APO-1/Fas) ligand.
AB  - The CD95 (APO-1/Fas) ligand (CD95L) mediates apoptosis in sensitive target cells,
      Ca(2+)-independent cytotoxicity of cells from perforin knock-out mice, and
      peripheral deletion of activated T cells through engagement of its cognate
      receptor CD95. Double-positive thymocytes show a high constitutive expression of
      CD95. Therefore, we used a model system and investigated whether negative
      selection through apoptosis might involve CD95/CD95L. We analyzed whether CD95L
      may induce antigen-specific deletion of double-positive thymocytes from mice
      transgenic for a lymphocytic choriomeningitis virus (LCMV)/H2b-specific T cell
      receptor (TCR). These cells are deleted in vitro upon addition of the LCMV
      peptide 33-41 in a major histocompatibility complex-class I-restricted fashion.
      Deletion was not blocked by soluble mouse and human CD95-Fc receptor decoys. CD95
      Fc receptor decoys, however, were effective in blocking apoptosis induced by
      mouse CD95L-transfected L929 cells in sensitive CD95+ target cells and in
      thymocytes. These results suggest that TCR-induced deletion of immature
      thymocytes in vitro is independent of CD95L. Thus, our data argue against a role
      of CD95L in negative selection of MHC-class I-restricted autoreactive thymocytes.

PMID- 7589107
TI  - Molecular characterization of human CD94: a type II membrane glycoprotein related
      to the C-type lectin superfamily.
AB  - Natural killer (NK) cells preferentially express several genes of the C-type
      lectin superfamily which have been implicated in the regulation of NK cell
      function. We demonstrate that CD94 is a type II membrane protein encoded by a
      unique gene of the C-type lectin superfamily. While homology of CD94 with the NK
      cell-associated NKR-P1 and NKG2 C-type lectin genes is limited to the structural
      motifs conserved in the carbohydrate recognition domain, all of these genes are
      on human chromosome 12, the syntenic of mouse chromosome 6, where genes of the NK
      complex (NKR-P1 and Ly-49) are located. An unexpected feature of CD94 is the
      essential absence of a cytoplasmic domain, implying that association with other
      receptors may be necessary for the function of this molecule.

PMID- 7589108
TI  - CD40-mediated lymphotoxin alpha expression in human B cells is tyrosine kinase
      dependent.
AB  - The cytokine lymphotoxin (LT)alpha is known to play a role in B cell activation.
      As the engagement of the B cell antigen CD40 is known to lead to B cell
      proliferation and differentiation, we studied LT alpha expression in human B
      cells after CD40 ligation. We demonstrate that anti-CD40 monoclonal antibody
      (mAb) induces strong LT alpha mRNA and surface-expression in human tonsil B
      cells. Induction of LT alpha mRNA and surface expression by CD40 ligation is
      inhibited by the protein tyrosine kinase (PTK) inhibitors herbimycin and
      genistein in a dose-dependent manner. The protein kinase C (PKC)-specific
      inhibitors sphingosine and bis-indolylmaleimide caused negligible inhibition of
      anti-CD40-induced LT alpha mRNA and surface expression. No inhibition is observed
      with the protein kinase (PKA) inhibitors H89 and HA1004. Cross-linking of the
      transmembrane phosphatase CD45 to CD40 by using goat-anti-mouse F(ab')2 fragments
      strongly inhibits CD40-mediated LT alpha expression in human B cells, confirming
      the role of PTK activation in CD40-mediated induction of LT alpha expression.
      Inhibitors of the serine/threonine protein phosphatases PP1 and PP2A, okadaic
      acid and calyculin induce LT alpha mRNA expression. In contrast, cyclosporin A,
      an inhibitor of the serine/threonine phosphatase calcineurin has no effect on
      anti-CD40-induced LT alpha expression. These results suggest that induction of LT
      alpha expression in B cells following engagement of CD40 involves activation of
      protein tyrosine kinases.

PMID- 7589111
TI  - A CD44 monoclonal antibody differentially regulates CD11a/CD18 binding to
      intercellular adhesion molecules CD54, CD102 and CD50.
AB  - We have made a monoclonal anti-CD44 antibody which is able to activate the
      leukocyte integrin CD11a/CD18. Activated T cells strongly aggregated, and the
      aggregation was shown to be intercellular adhesion molecule (ICAM)-1 (CD54) and
      ICAM-2 (CD102) dependent. Using purified ICAM coated on plastic, only binding to
      ICAM-1 was increased by the CD44 antibody, whereas activation by phorbol ester
      increased binding to both ICAM-1 and ICAM-3. The binding to ICAM-2 was not
      affected by either treatment. These findings show that the CD11a/CD18 integrin
      can be activated in a ligand-specific manner by engagement of CD44.

PMID- 7589110
TI  - Role of N-linked glycosylation in expression of E-selectin on human endothelial
      cells.
AB  - E-selectin is a cytokine-inducible membrane glycoprotein capable of mediating
      adhesion of leukocytes to endothelial cells. It is highly glycosylated,
      containing 11 sites for N-linked glycosylation. N-Glycosylation of E-selectin was
      analyzed by endoglycosidase treatment. Analysis of immunoprecipitated E-selectin
      from human umbilical vein endothelial cells (HUVEC) by polyacrylamide gel
      electrophoresis in the presence of sodium dodecylsulfate showed that E-selectin
      was completely resistant to endoglycosidase H, but sensitive to peptide N
      glycanase F digestion. This suggested that all N-linked oligosaccharide chains
      were of the complex type. The role of N-linked glycosylation in surface
      expression and secretion of E-selectin was studied using interleukin-1-stimulated
      HUVEC, cultured in the presence of the soluble glycosylation inhibitors
      tunicamycin or castanospermine. Cell surface expression was analyzed by indirect
      flow cytometry. N-Glycosylation was blocked by tunicamycin, and resulted in a
      significantly reduced surface expression of E-selectin, whereas castanospermine
      only marginally reduced E-selectin expression. The deglycosylated forms of E
      selectin were also found to be fully capable of mediating adhesion of HT-29 cells
      in vitro. In conclusion, these studies show that E-selectin is heavily
      glycosylated with complex type N-linked oligosaccharides and that N-glycosylation
      is important for expression of E-selectin on human endothelial cells.

PMID- 7589109
TI  - CD4 and CD45 regulate qualitatively distinct patterns of calcium mobilization in
      individual CD4+ T cells.
AB  - An early consequence of T cell activation is an increase in intracellular calcium
      concentration. Recent advances in video laser microscopic techniques enable the
      examination of individual cells over time following stimulation. Such studies
      have revealed that cells can undergo qualitatively distinct patterns of calcium
      mobilization, suggesting that different patterns of calcium flux may be
      associated with different signaling pathways and may differentially affect late
      events in cell activation. In this report, we identify distinct patterns of
      calcium mobilization in CD4+ T cells following the antibody-mediated cross
      linking of either CD3 or CD4, or following the cross-linking of both CD3 and CD4
      simultaneously. These effects can be further modified by the cross-linking of
      CD45. We find that antibody cross-linking of CD3 alone induces a single spike in
      the vast majority of cells shortly after the addition of the cross-linking
      antibody. In contrast, cross-linking CD4 alone induces a delayed pattern of
      repetitive calcium spikes which are decreased in amplitude compared to CD3 cross
      linking. Simultaneous cross-linking of CD3 and CD4 induces a sustained increase
      in intracellular calcium mobilization which is dependent on the presence of
      extracellular calcium. This sustained increase in intracellular calcium
      concentration is also seen following physiologic cross-linking of CD3 and CD4
      after T cell interaction with specific antigen and antigen-presenting cells.
      Finally, the simultaneous cross-linking of CD45, CD3 and CD4 abrogates the
      sustained increase in calcium seen following CD3 and CD4 cross-linking. These
      results suggest that the qualitative nature of T cell receptor signaling can be
      modulated by the molecular association of other signaling molecules, which may be
      part of the T cell receptor complex or not.

PMID- 7589114
TI  - T cell receptor diversity in alloreactive responses against HLA-B27 (B*2705) is
      limited by multiple-level restrictions in both alpha and beta chains.
AB  - The T cell receptors (TCR) in HLA-B27 (B*2705) alloreactivity were analyzed in
      cytotoxic T lymphocytes (CTL) from two individuals. Non-random usage was found in
      V beta, N+D beta, V alpha, and J alpha, but not in J beta segments or N alpha
      regions. V beta segments from homology subgroup 4 were predominant and not
      associated to a particular donor or fine specificity, suggesting involvement in
      recognizing the HLA-B27 molecule. In contrast, preferential V alpha usage was
      associated with particular individuals and fine specificities, indicating
      distinct V beta and V alpha recruitment and contribution to allorecognition.
      Recurrent N+D beta motifs and J alpha segments, even from different donors,
      limited junctional diversity, suggesting that CDR3 usage was determined by the
      alloantigenic epitope independently of individuals. TCR were selected differently
      at various levels, as indicated by the following findings. Four clonotypes with
      similar fine specificity had identical beta and unrelated alpha chains. Similar
      alpha were associated with unrelated beta chains, and vice versa. CTL using V
      beta subgroup 4 did not globally show concomitant predominance of other TCR
      elements. V alpha 7, one of the preferred V alpha segments, was always associated
      with V beta subgroups other than 4. Sometimes, a TCR showed homology in elements
      of one chain to a second TCR or group of TCR, and to another in the other chain.
      These results are best explained by differential selection of TCR elements by
      different epitopes, providing a key to the inner structure of allospecific TCR
      repertoires.

PMID- 7589112
TI  - Differential effects of interleukin-10 on the expression of HLA class II and CD1
      molecules induced by granulocyte/macrophage colony-stimulating factor/interleukin
      4.
AB  - Interleukin (IL)-10 down-regulates HLA class II molecules, whether constitutively
      expressed or up-regulated by interferon-gamma or IL-4 on monocytes but not on B
      lymphocytes. In this study we show that IL-10 does not inhibit HLA class II
      expression induced by the combination granulocyte/macrophage colony-stimulating
      factor and IL-4 on monocytes, although it simultaneously abrogates the expression
      of CD1 molecules induced by the same combination of cytokines. CD1 molecules can
      act as element of genetic restriction for CD4- CD8- T lymphocytes, and the
      suppression of CD1 expression by IL-10 abolished antigen presentation to CD1
      restricted CD4- CD8- T cell receptor-positive T cells. Although HLA class II
      expression was not down-regulated by IL-10, the antigen specific proliferative
      response of CD4+ T cells was nevertheless decreased. This was not caused by down
      regulation of known co-stimulatory molecules such as B7.1, B7.2 and ICAM-1. IL-10
      decreased the antigen specific proliferative response further by directly
      influencing the T lymphocytes. Our results indicate that IL-10 exerts some of its
      immunoregulatory functions by differential modulation of antigen presenting
      molecules, induced by the same combination of cytokines.

PMID- 7589115
TI  - Activation and hapten inhibition of mast cells sensitized with monoclonal IgE
      anti-penicillin antibodies: evidence for two-site recognition of the penicillin
      derived determinant.
AB  - We utilized an in vitro mast cell activation assay and hapten inhibition of
      mediator release to characterize the fine specificity of two IgE anti-penicillin
      monoclonal antibodies (mAb). Cultured mouse mast cells were passively sensitized
      with IgE mAb anti-benzylpenicillin (BP) or anti-amoxicillin (AX) and challenged
      with a range of penicillin-human serum albumin (HSA) conjugates. Mast cells
      sensitized with IgE anti-BP degranulated in response to BP-HSA, but not to AX-HSA
      or ampicillin(AMP)-HSA, whereas mast cells sensitized with IgE anti-AX responded
      to AX-HSA but not to BP-HSA or AMP-HSA. Because BP, AX and AMP differ chemically
      only in the structure of their side chain, these results show that this part of
      the drug molecule is essential for recognition by IgE antibody. Unexpectedly,
      although IgE-sensitized mast cells responded to only one penicillin in protein
      conjugated form, antigen-induced degranulation was inhibited by the monomeric
      derivative of more than one penicillin. Furthermore, antigen activation of IgE
      sensitized cells was inhibited, although less potently, by haptens representative
      of the specific penicillin side chain or the binuclear portion of the drug
      molecule. These patterns of recognition and hapten inhibition were also seen in
      solid-phase enzyme-linked immunosorbent assay (ELISA), although all haptenic
      inhibitors were approximately 100 times less potent in the ELISA compared to the
      mast cell assay. To explain these findings we propose a model in which IgE
      binding to penicillin-protein antigen is dependent on recognition of two distinct
      epitopes on the drug molecule: the first comprising the side chain, and the
      second comprising the binuclear portion plus the proximal region of the side
      chain. This two-site hypothesis provides a generally applicable model of antibody
      recognition of penicillins and provides a rational basis for understanding the
      specificity and cross-reactivity of IgE-mediated allergic reactions to
      penicillins.

PMID- 7589113
TI  - CD34-positive early human thymocytes: T cell receptor and cytokine receptor gene
      expression.
AB  - CD34, a stem cell marker, has been shown to be expressed on human CD3-CD4-CD8-
      (triple-negative; TN) thymocytes. Phenotypic and functional analyses suggest the
      following differentiation sequence: CD34+1-3-4-8(-)--> CD34+1+3-4 +/- 8(-)-->CD34
      1+3-4+8(+/-)-->CD34-1++3-4+8+. In this report, we examined cytokine receptor gene
      expression on these subsets by reverse transcription-polymerase chain reaction
      analysis (RT-PCR). We were able to detect interleukin-7 receptor (IL-7R), c-kit
      and IL-2R gamma in all CD34+ thymocyte subsets, consistent with previous
      functional studies. We found IL-1R, granulocyte/macrophage colony-stimulating
      factor receptor-alpha and IL-4R transcripts in CD3- and CD34+ subsets. Secondly,
      we investigated T cell receptor (TCR)-delta and -beta gene rearrangement and
      transcription in CD34+ thymocytes. Our results show that a full-length TCR-delta
      transcript and the recombination activating genes RAG-1 and RAG-2 mRNA were
      already expressed in the CD34+1- subset. Mature V beta-containing TCR transcripts
      were also detected in the CD34+1+ subset, but not in the CD1- fraction.
      Furthermore, PCR analysis of D-J beta gene rearrangements showed that > or = 70%
      of CD34+1- cells are in a TCR beta germ-line configuration, although D-J beta
      recombination had already started in this population.

PMID- 7589116
TI  - Macrophage-T cell interaction in experimental visceral leishmaniasis: failure to
      express costimulatory molecules on Leishmania-infected macrophages and its
      implication in the suppression of cell-mediated immunity.
AB  - The most important immunopathological consequence of infection with Leishmania
      seen in murine and human hosts is the suppression of T cell-mediated immune
      responses to both mitogens and leishmanial antigens. It has been suggested that
      this suppression is mediated by macrophages, either by defective antigen
      processing and presentation or by the elaboration of suppressive mediators like
      prostaglandins. Optimum activation of T helper cells requires not only T cell
      receptor occupancy by the antigen-Ia complex, but also costimulatory signals
      provided by the antigen-presenting cells. We investigated the status of several
      costimulatory molecules on infected macrophages from both genetically susceptible
      BALB/c and resistant C57BL/6 mice. Our results demonstrate that upon
      parasitization, the macrophages become unable to deliver costimulatory signals to
      T helper cells, and that this effects is mediated by prostaglandins, as the
      inhibition of its synthesis by indomethacin recovered the defect. Upon infection
      with L. donovani, B7-1 expression was decreased, while ICAM-1 was marginally
      increased in BALB/c macrophages and there was no significant change in the
      expression of B7-1 and ICAM-1 in Leishmania-infected C57BL/6 macrophages.
      Expression of VCAM-1 did not change during infection. This selective alteration
      in the expression of costimulatory molecules on L. donovani-infected BALB/c
      macrophages was caused by the living parasite, as shown by the fact that killing
      of the parasites by stibogluconate led to no alteration in the levels of
      costimulatory molecules. We found that the change in B7-1 expression on the
      surface of infected macrophages resulted in the inhibition of delayed-type
      hypersensitivity-mediating functions of T helper cells from BALB/c mice. The
      results described in this study not only throw light on the possible mechanism of
      leishmanial pathogenesis, but also open up the possibility of immunotherapy of
      leishmaniasis by selective manipulation of costimulatory molecules.

PMID- 7589117
TI  - Various V-J rearrangement efficiencies shape the mouse lambda B cell repertoire.
AB  - The diversity of the B cell repertoire of C kappa knockout mice is limited by the
      expression of four lambda light chain types. Among the spleen B cells, lambda 1
      is expressed by the majority (58%) of cells, and lambda 3 by the minority (8%),
      while lambda 2 (V2) and lambda 2 (Vx) are expressed in intermediate quantities
      (18% and 16%, respectively). To assess the influence of mechanistic pressures on
      the lambda subtype distribution, the proportions of the different lambda
      rearrangements were determined in various B cell subpopulations divided on the
      basis of the lambda subtype expressed, and the V lambda J lambda junction
      sequences were studied at different steps of B cell differentiation (pre-B,
      immature and mature B cells). The data show that (1) the ratio of productive/non
      productive VJ junctions is determined by the nature of the lambda segments that
      are rearranged as can be observed in the pre-B cells, (2) V1-J1 non-productive
      rearrangements are often found in the lambda 1-negative B cells in the periphery,
      and (3) V1J3 junctions are often non-productive regardless of the nature of the
      cells analyzed. Our results, therefore, suggest that a strong probability of
      initiating a V1-J1 rearrangement and a weak probability of giving a productive
      V1J3 junction are responsible for the lambda 1 dominance and the lambda 3 under
      expression, respectively. The intermediate proportion of lambda 2(V2) subtype is
      most likely due to a probability of obtaining a productive joint that is better
      than that for V1J3 and a probability of initiating a rearrangement that is lower
      than that for V1J1. However, the lambda 2(Vx) cell proportion cannot be
      determined only by these parameters.

PMID- 7589118
TI  - Involvement of NAK-1, the human nur77 homologue, in surface IgM-mediated
      apoptosis in Burkitt lymphoma cell line BL41.
AB  - The induction of apoptosis via surface IgM (sIgM) in immature B cells requires de
      novo transcription. To investigate the regulation of activation-induced cell
      death (AICD) in B cells we used a cell line model consisting of an Epstein-Barr
      virus-negative Burkitt lymphoma cell line (BL41), which is highly sensitive, and
      a subclone which is resistant to sIgM-mediated apoptosis (BL41/B5). Resistance in
      this cell line was not due to down-regulation of sIgM or functional impairment in
      signal transduction of the surface Ig complex. The zinc finger transcription
      factor nur77 has been implicated to play an important role in CD3-mediated
      apoptosis in murine T cells. We were able to demonstrate that surface IgM
      ligation and subsequent apoptosis in BL41 cells is associated with a concomitant
      induction of NAK-1, the human nur77 homologue. Induction of NAK-1 mRNA and DNA
      binding activity in the nucleus could be readily observed by means of Northern
      blot and electrophoretic mobility shift assay, respectively. In contrast, the
      resistant clone BL41/B5 did not show any NAK-1 expression upon stimulation. This
      suggests a role for NAK-1 in sIgM-mediated apoptosis of immature B cells.

PMID- 7589119
TI  - The majority of murine VH12-expressing B cells are excluded from the peripheral
      repertoire in adults.
AB  - We have previously demonstrated that at birth most productive (P) VH12
      rearrangements in B10.H-2aH-4bp/Wts (2a4b) mice encode a ten-amino acid CDR3, and
      that a significant fraction of the expected repertoire is absent. We have now
      examined the adult VH12 CDR3 repertoire involving all four JH gene segments in
      both peritoneum and spleen. Of the 74 P VH12 rearrangements from these tissues 67
      encode a CDR3 of ten amino acids and include a Gly in the fourth position
      (designated 10/G4). Most of these rearrangements appear to derive from
      phosphatidylcholine (PtC)-specific B cells, which also have a 10/G4 VHCDR3, since
      few 10/G4 P rearrangements were present in spleen cells depleted of PtC-specific
      B cells. Thus, the VH12 B cell repertoire in adult mice is largely restricted to
      the use of a single CDR3 motif and to a single antigen specificity. This bias
      results from two selection events: (1) selective exclusion of most VH12 B cells
      from the peripheral repertoire, and (2) clonal expansion in the periphery of VH12
      B cells that have a 10/G4 VHCDR3 and bind PtC. Analysis of VH12-JH1
      rearrangements in viable motheaten (mev/mev) mice, which have an abnormal B cell
      repertoire due to a defective phosphatase (Hcph) and have barely detectable
      numbers of PtC-specific B cells, indicates that selective exclusion of VH12 B
      cells from the peripheral repertoire occurs normally, but that clonal expansion
      of 10/G4 VH12 B cells is minimal. This is evidence that the selective exclusion
      of VH12 B cells from the peripheral repertoire and the clonal expansion of VH12 B
      cells with a 10/G4 CDR3 are due to independent signaling events.

PMID- 7589122
TI  - Stimulation of a memory B cell response does not require primed helper T cells.
AB  - The use of universally immunogenic T cell epitopes, such as those identified in
      tetanus toxin or malaria circumsporozoite protein, could represent a major
      improvement in the development of synthetic vaccines. However, one limitation of
      this approach is the lack of T cell cross-reactivity between the vaccine and the
      pathogen. To determine whether the memory B cell response elicited by
      immunization with a synthetic peptide containing a B cell epitope linked to a T
      cell epitope can be restimulated by the same B cell epitope linked to different T
      cell epitope(s), we used a synthetic peptide which contains non-overlapping B and
      T cell determinants from hepatitis B surface antigen (HBsAg) of hepatitis B virus
      (HBV). The results of this study clearly show that primed T cells can increase
      the antibody response against a B cell epitope linked to the priming T cell
      determinant. However, the antibody response obtained was weaker than that
      obtained after two injections of the peptide containing both B and T cell
      epitopes, showing the important role played by memory B cells in secondary
      antibody responses. Moreover, a strong antibody response against the B cell
      epitope was elicited by boosting mice with the B cell epitope linked to a
      heterologous carrier, thus demonstrating that a strong B cell memory response can
      be revealed in the absence of primed T cells. These results therefore provide new
      important information for the design of synthetic or recombinant vaccines.

PMID- 7589120
TI  - Evidence for Th2 cell-mediated suppression of antibody responses in transgenic,
      beef insulin-tolerant mice.
AB  - Clonal deletion, anergy and suppression have all been considered mechanisms of
      immunological tolerance. Although adoptive transfer of immunosuppression has been
      shown to occur in the periphery, particularly for transplantation tolerance, it
      has proven difficult to characterize this phenomenon further, due to the lack of
      suppressor T cell clones. To characterize tolerance towards a physiological
      soluble antigen, we constructed beef insulin (BI) transgenic (Tg) BALB/c (H-2d)
      mice, in which the BI transgene is expressed in pancreatic beta cells. These Tg
      mice were tolerant to BI immunization at the level of both humoral and cell
      mediated immune responses. Adoptive transfer of splenocytes from Tg mice into
      normal syngeneic BALB/c mice demonstrated that the reduction in antibody
      production is regulated by transferred T cells. The cytokine profile of T cell
      clones obtained after selection in vitro demonstrated dominant Th1 clones from
      normal non-Tg mice and dominant Th2 clones from Tg mice. Some Th2 clones (CD4+)
      from Tg mice produced significant suppression of antibody production after
      adoptive transfer into normal syngeneic BALB/c mice. These data confirm the
      existence of Th2 regulatory T cells in vivo in a model of peripheral tolerance to
      a physiological soluble antigen as a potential mechanism for self tolerance.

PMID- 7589123
TI  - Superantigens initiate cognate CD4+ T cell/B cell interactions leading to early
      activation and proliferation of B cells.
AB  - Dimerization or even multimerization of various receptors is commonly required
      for signal transduction. We report here that clustering of major
      histocompatibility complex class II molecules in human B cells by biotinylated
      staphylococcal enterotoxin A (SEA) cross-linked with avidin induces an increase
      in the level of intracellular calcium. This response was abolished by prior
      treatment with protein tyrosine kinase (PTK) inhibitors, suggesting that SEA
      triggered calcium mobilization in B cells is probably dependent on the activation
      of PTK. The implication of PTK in SEA-induced early B cell activation was then
      confirmed by demonstrating that cross-linked SEA induces a significant increase
      in the level of tyrosine phosphorylation in B cells. The requirement of
      biotinavidin cross-linking in SEA-induced calcium mobilization in B cells can be
      fulfilled by the addition CD4+ T cells, suggesting a role for CD4 molecules.
      Using the murine CD4- T cell hybridoma 3DT, or its derivative I1B3 transfected
      with human CD4 that both express SEA-specific TCR, we confirmed the CD4
      requirement for B cell calcium mobilization and that both specific TCR and CD4
      molecules are required in early events of B cell activation induced by SEA. The
      role of CD4 in SEA-induced B cell proliferation was then investigated. SEA
      stimulated B cells proliferated in the presence of CD4+ T cells, whereas no
      response was observed in the presence of CD8+ T cells. The addition of clone I1B3
      CD4+ T cells failed to fulfill the requirement of CD4+ T cells in SEA-induced B
      cell proliferation, indicating the possible involvement of other CD4+ T cell
      surface molecules in this response. This issue is currently under investigation.

PMID- 7589121
TI  - Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for
      leukocyte function antigen-1 on human blood dendritic cells.
AB  - Dendritic cells (DC) are potent stimulators of primary T lymphocyte responses to
      foreign antigen. The initial DC-T lymphocyte interaction involves the binding of
      the adhesion molecule leukocyte function antigen-1 (LFA-1; CD11a/CD18) on the T
      lymphocyte to an intercellular adhesion molecule (ICAM) on the DC. Although blood
      and tonsil DC express ICAM-1 (CD54) and ICAM-2 (CD102) on their surface, anti
      ICAM-1 and anti-ICAM-2 monoclonal antibodies (mAb) have little inhibitory
      activity on the DC-stimulated mixed leukocyte reaction (MLR). We therefore
      examined the expression of the more recently identified LFA-1 ligand, ICAM-3
      (CD50), in comparison to ICAM-1 and ICAM-2 on blood DC and sought a functional
      role for ICAM-3 in DC-mediated T lymphocyte responses. Resting blood DC expressed
      significantly more ICAM-3 than ICAM-1 or ICAM-2 as assessed by flow cytometry.
      Treatment of resting DC with interferon-gamma led to increased expression of ICAM
      1; however, ICAM-2 and ICAM-3 levels remained relatively constant. Solid-phase
      recombinant chimeric molecules ICAM-1-, ICAM-2- and ICAM-3-Fc were able to co
      stimulate CD4+ T lymphocyte proliferation in conjunction with suboptimal solid
      phase CD3 mAb 64.1. However, the anti-ICAM-3 mAb CAL 3.10 inhibited a DC
      stimulated MLR to a greater extent than anti-ICAM-1 or anti-ICAM-2 reagents and
      appeared to act by blocking the DC ICAM-3- T lymphocyte LFA-1 interaction. As
      ICAM-3 is the predominant LFA-1 ligand on resting blood DC, we postulate that DC
      may utilize ICAM-3 for initial DC- T lymphocyte interactions, and that ICAM-1,
      which is up-regulated upon DC activation, and/or ICAM-2, may contribute to DC
      migration or later phases of the T lymphocyte activation process.

PMID- 7589124
TI  - Sialyl LewisX carbohydrate is expressed differentially during avian lymphoid cell
      development.
AB  - Sialyl LewisX is a carbohydrate moiety involved in the regulation of white blood
      cell adhesion to endothelial cells. In this work, we have studied the expression,
      localization and function of sialyl LewisX carbohydrate on maturing B and T cells
      and the stroma of avian bursa, thymus and spleen as well as the role of sialyl
      LewisX in the generation of immune response and formation of germinal centers in
      the spleen. The expression of sialyl LewisX on bursal B cells decreases during
      the embryonic period, while on T cells it remains at a stable low level
      throughout their thymic development. Immediately after hatching, by which time
      the expression of sialyl LewisX on bursal B cells has already decreased, the
      stromal microenvironment of the bursa starts to express it. After hatching,
      sialyl LewisX is localized exclusively in the medullae of the follicles and the
      number of sialyl LewisX-positive follicles declines gradually during the
      following weeks. Thymic stroma does not express sialyl LewisX at any stage of
      development. In spleen, sialyl LewisX is expressed on a number of B and T cells
      as well as on other cell types in a way that seems not to be restricted to any
      structurally defined area. The cells or stroma of the germinal centers, however,
      do not express sialyl LewisX. When given simultaneously with an immunizing agent,
      anti-sialyl LewisX monoclonal antibody reduced the formation of germinal centers
      and suppressed antibody response in young birds. These results demonstrate that
      sialyl LewisX-bearing cell surface molecules are required during the generation
      of immune responses. They also suggest a role for sialyl LewisX in B cell
      maturation.

PMID- 7589126
TI  - Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells.
AB  - MRL/lpr mice develop a systemic autoimmune disease similar to systemic lupus
      erythematosus in humans. The mice show progressive lymphadenopathy due to the
      accumulation of an unusual population of CD4-8-(DN) B220+ alpha beta+ T cells. We
      bred MRL/lpr mice with mice lacking CD4+ or CD8+ T cells by gene targeting via
      homologous recombination in embryonal stem cells to determine the roles of these
      cells in the autoimmune disease. No difference in survival or autoantibody levels
      was noted between CD8-/-lpr and littermate controls. Interestingly, these CD8-/-
      lpr mice have a reduced level of B220+ DN T cells despite the fact that the
      degree of lymphadenopathy was unaltered. CD4-/- lpr mice had a diminished
      autoimmune disease with a reduction in autoantibody production and skin
      vasculitits, and increased survival compared to littermate controls. However, CD4
      /- lpr mice had an enhanced splenomegaly that developed massively by 16-20 weeks
      of age (5 to 8 greater than lpr control mice) due to the accumulation of DN B220+
      T cells. In addition, there were no differences in peripheral lymph node
      enlargement, although the proportion of DN B220+ T cells was about twofold higher
      in the CD4-/- lpr mice. These cells were phenotypically identical to the DN
      population in control lpr mice, indicating that the accumulating DN T cells can
      be dissociated from the autoimmune disease in these mice. Collectively, our
      results reveal that the autoimmune disease is dependent on CD4+, but not CD8+ T
      cells, and that many of the B220+ DN T cells traverse a CD8 developmental
      pathway.

PMID- 7589125
TI  - CD8+ type 1 CD44hi CD45 RBlo T lymphocytes control intracellular Brucella abortus
      infection as demonstrated in major histocompatibility complex class I- and class
      II-deficient mice.
AB  - Genetically engineered mice with a targeted disruption in the beta 2
      microglobulin (beta 2-m) gene or the H2-I-A beta chain (A beta) which lack
      functional CD8+ or CD4+ T cells, respectively, were used to assess the role of T
      cell subsets in Brucella abortus infection. Murine brucellosis was markedly
      exacerbated in beta 2-m-deficient mice (beta 2-m-/-) compared to A beta mutant (A
      beta-/-) or C57BL/6 mice, strongly indicating that optimal resistance to B.
      abortus requires CD8+ T cells. Splenocytes from Brucella-primed beta 2-m-/-, A
      beta-/- and C57BL/6 mice exhibited a type 1 cytokine profile marked by elevated
      IFN-gamma mRNA expression and protein production, and basal levels of IL-2 and IL
      4 transcripts. B. abortus did not induce secretion of TGF-beta 1, but substantial
      IL-10 activity was detected in spleen cell supernatants from all mouse strains
      studied. CD8+ T cells from A beta-/- and C57BL/6 mice displayed a CD44hi CD45RBlo
      phenotype and a type 1 cytokine transcription profile featuring high levels of
      IFN-gamma mRNA. Additionally, we have shown the ability of C57BL/6 CD8+ CTL to
      kill Brucella-infected macrophages. This study illustrates the predominant role
      of MHC class I-restricted T cells in controlling B. abortus infection.

PMID- 7589127
TI  - Regulatory T cells in thymic epithelium-induced tolerance. I. Suppression of
      mature peripheral non-tolerant T cells.
AB  - Athymic mice grafted at birth with allogeneic thymic epithelium (TE) display life
      long tolerance to tissue grafts of the TE donor strain, in spite of harboring
      peripheral T cells capable of rejecting those grafts. Tolerance is maintained in
      these chimeras by TE-specific regulatory CD4 T cells. We presently address the
      quantification and the mechanisms of this dominant tolerance process. C57BL/6
      mice containing variable but defined numbers of peripheral, resident T cells
      received cell transfers of graded numbers of peripheral T cells from B6(BALB E10)
      chimeras (C57BL/6 nude mice grafted with TE from 10-day-old BALB/c embryos),
      resulting in a series of animals containing a wide range of donor (tolerant)
      versus host (non-tolerant) T cell chimerism. Increasing the relative
      representation of donor T cells results in a progressive delay in the rejection
      of BALB/c skin grafts, life-long tolerance being achieved at a ratio of tolerant
      and non-tolerant T cell populations of 1. In recipients displaying full
      tolerance, graft-reactive non-tolerant T cells were not deleted, anergized or
      committed to noninflammatory functions. Thus, sorted host T cells from tolerant
      recipients readily rejected BALB/c skin grafts upon transfer to immunodeficient
      animals. Finally, measurements of "helper" and inflammatory activities, as well
      as interleukin-4 and interferon-gamma production, failed to discriminate between
      T cell populations from tolerant and non-tolerant animals after specific in vitro
      stimulation. We conclude that: (a) TE-selected regulatory T cells can suppress,
      in a quantitative manner, in vivo T cell responses against major and minor
      histocompatibility antigens expressed by the TE and, (b) this suppressive
      activity neither inactivates mature non-tolerant T cells, nor does it seem to
      drive their differentiation along noninflammatory pathways.

PMID- 7589129
TI  - Extensive allelic sequence variation in the J region of the human immunoglobulin
      heavy chain gene locus.
AB  - During the initial stages of B lymphocyte differentiation heavy chain variable
      (VH), diversity (DH) and joining (JH) gene segments recombine to form a
      functional heavy chain variable region (VDJ) gene. Evidence for genetic
      polymorphism of the human JH gene segments has been obtained from mature
      rearranged VDJ sequences. We conducted an analysis of the published rearranged JH
      gene sequences and found that the JH alleles present in the two published germ
      line JH region sequences were rare (approx. 2%) in the rearranged sequences. As
      an attempt to explain this discrepancy a 2.5-kb strech of DNA containing all the
      six heavy chain JH region genes and the most 3' DH gene segment, DHQ52, was
      amplified by the polymerase chain reaction from 39 individuals and analyzed for
      restriction fragment length polymorphism. Five new JH region haplotypes were
      found and sequenced. These new haplotypes contained the coding segment alleles
      that were frequent in antibody genes. Surprisingly, a high number of interallelic
      differencies in the non-coding sequence was found between the new and the two
      previously published haplotypes implying that the haplotypes had been separated
      early in evolution. In this respect the JH locus resembles HLA loci.

PMID- 7589128
TI  - Normal clonal expansion but impaired Fas-mediated cell death and anergy induction
      in interleukin-2-deficient mice.
AB  - Despite a normal development of all major lymphoid subsets, with time,
      interleukin-2 (IL-2)-deficient mice develop a fatal immunopathology. The disease
      phenotype is characterized by lymphoadenopathy, splenomegaly, T cell infiltration
      of various organs, overproduction of a number of cytokines and autoantibody
      formation. Phenotypically, CD4+ and CD8+ T cells exhibit features characteristic
      of antigenically experienced cells. The accumulation of cells with a memory
      phenotype together with the previous suggestion of an involvement of IL-2 in the
      termination phase of immune responses prompted us to study the fate of
      superantigen-reactive T cells in IL-2-deficient mice in comparison to their IL-2
      producing littermates. We show that expansion in vivo of CD4+ and, to a lesser
      extent, CD8+ T cells reactive to the superantigens staphylococcal enterotoxin A
      and B (SEA and SEB) proceeds normally in the absence of IL-2, but that fewer CD4+
      cells are subsequently deleted. The residual superantigen-reactive cells fail to
      become anergic as measured by proliferation in vitro in response to the same
      superantigen. T cell blasts generated in vitro from lymph node cells of IL-2
      deficient mice by superantigen stimulation in the absence of exogenous IL-2 also
      fail to become anergic. In contrast to cells from IL-2-producing littermates,
      they do not exhibit Fas-induced apoptosis when cultured on anti-Fas antibody
      coated plates, although Fas expression by IL-2-deficient cells is normal or even
      elevated compared to the IL-2-producing control cells. The data suggest that
      activation of T cells in the absence of IL-2 fails to generate a signal which is
      necessary to activate the apoptotic pathway and thus leads to an accumulation of
      antigen-experienced cells and the chronic inflammatory responses observed in IL-2
      deficient mice.

PMID- 7589130
TI  - Fetal VDJ gene repertoire in rabbit: evidence for preferential rearrangement of
      VH1.
AB  - B cells in rabbit preferentially utilize the 3'-most VH gene, VH1, in VDJ genes.
      To determine whether the preferential utilization of VH1 results from
      preferential rearrangement, we examined VH gene usage in nonproductive VDJ gene
      rearrangements, genes that would not be influenced by antigen selection. Since
      nonproductive VDJ gene rearrangements are found infrequently in neonatal and
      adult rabbits, we examined the VDJ gene rearrangements during early fetal
      development. According to nested-primer polymerase chain reaction analyses, VDJ
      genes in fetal liver appeared around day 14 of gestation and nucleotide sequence
      analyses of VDJ genes cloned from 14- to 28-day-old fetuses showed that many of
      the genes were nonproductive. We found that most of these nonproductive genes had
      utilized VH1 indicating to us that the preferential utilization of VH1 is due to
      preferential rearrangement. We compared the nucleotide sequence of the promoter
      region of VH1 with sequences of several other unutilized and infrequently
      utilized VH genes and found that the core transcriptional factor motifs were
      similar in all VH promoters examined. We suggest that transcriptional activity of
      the VH1 promoter region does not explain the preferential rearrangement of VH1.

PMID- 7589131
TI  - Peptide-specific activation of cytolytic CD4+ T lymphocytes against tumor cells
      bearing mutated epitopes of K-ras p21.
AB  - Alterations in the ras p21 protein have been associated with both rodent and
      human neoplasia. Thus, mutated ras p21 proteins may bear unique antigenic
      epitopes for immune recognition, such as by T cells, which have been implicated
      in host antitumor activity. Synthetic peptides that mimic segments of mutated ras
      p21 have been reported to be immunogenic in mice in vivo, although detailed
      functional analyses remains undefined. Here, in a murine model, we explored and
      characterized distinct effector properties of host-derived T lymphocytes reactive
      to mutated ras peptides, which was consistent with the CD4+ T helper type 1 (Th1)
      subset. BALB/c mice (H-2d) were immunized with a purified peptide, 13 amino acids
      in length, containing the substitution of Gly (G12) to Val (V12) at position 12,
      which is commonly found in human carcinomas. An alpha beta T cell receptor
      positive, CD3+, CD4+, CD8- T cell line was established, which expressed peptide
      specific proliferation. Cytokine assays revealed the production of interleukin-2,
      interferon-gamma, tumor necrosis factor and granulocyte-macrophage colony
      stimulating factor. Moreover, antigen-specific cytotoxicity was demonstrable
      against: (1) Iad-bearing A20 tumor cells incubated with exogenously bound V12
      peptide; and (2) A20 tumor cells transduced with the K-ras p21 oncogene encoding
      the corresponding point mutation. CD4(+)-mediated cytotoxicity was major
      histocompatibility complex (MHC) class II-restricted, as revealed by the absence
      of lysis against MHC class II- P815 targets, inhibition of A20 lysis with anti
      Iad monoclonal antibodies, and induction of lysis against L cell targets
      transfected with E alpha A beta d. Independent isolation of a second CD4+ V12
      line revealed a very similar cytolytic and MHC class II-restricted profile.
      Overall, these data demonstrated that peptide immunization produced a CD4+ Th1
      response that specifically recognized tumor cells expressing endogenous activated
      K-ras epitopes, which may have implications for the development of peptide-based
      active immunotherapies.

PMID- 7589133
TI  - Incorporation of major histocompatibility complex--encoded subunits LMP2 and LMP7
      changes the quality of the 20S proteasome polypeptide processing products
      independent of interferon-gamma.
AB  - The 20S proteasome is the enzyme complex responsible for the processing of
      antigens bound by major histocompatibility complex class I molecules. The role of
      the interferon-gamma (IFN-gamma)-inducible proteasome subunits LMP2 and LMP7 in
      this process is, however, still controversial. We have studied the effects of IFN
      gamma-independent LMP incorporation on the quality of peptides processed from the
      murine cytomegalovirus IE pp89 25-mer polypeptide substrate through dual
      cleavages by 20S proteasomes. The incorporation of a single LMP subunit or both
      LMP2 and LMP7 induces changes in 20S proteasome subunit stoichiometry, alters its
      cleavage site preference and in consequence, the quality of the generated
      peptides. When the several hydrolytic activities are tested with short
      fluorogenic peptide substrates, the Vmax, S0.5 (Km), or both values of 20S
      proteasomes are altered, depending on the combination of LMP. There exists,
      however, no obvious correlation between the observed changes in hydrolytic
      activities against short fluorogenic peptides and the changes in dual cleavage
      site usage within the 25-mer polypeptide substrate. As judged from the calculated
      Hill coefficients, the presence of both LMP subunits induces a drastic increase
      in positive cooperativity between the proteasome subunits.

PMID- 7589132
TI  - Analysis of the natural human IgG antibody repertoire: life-long stability of
      reactivities towards self antigens contrasts with age-dependent diversification
      of reactivities against bacterial antigens.
AB  - We used a quantitative immunoblotting technique to analyze the repertoires of IgG
      antibody reactivities in the serum of healthy young children, young adult males
      and aged males with self and non-self antigens. Densitometric patterns of
      reactivity of purified IgG with self antigens were highly conserved between
      individuals within a given age group and across age groups. Inter-individual
      differences were observed, however, upon analysis of self reactivities of IgG in
      whole serum. A striking heterogeneity between individuals within a given age
      group and across age groups characterized the reactivity of purified IgG and of
      IgG in whole serum with bacterial antigens. Inter-individual differences were
      more marked among aged individuals than among individuals of other age groups.
      Analysis of variances of reactivities of IgG with bacterial antigens further
      demonstrated an increased diversity of repertoires of aged donors compared with
      those of young adults and children. Our results document the stability of the
      self-reactive repertoires of IgG throughout life, which contrasts with the
      diversification of the repertoire of IgG antibody reactivities directed toward
      foreign antigens with aging. These findings support the concept that self
      reactive antibody repertoires are positively selected throughout life by a
      restricted set of self antigens shared by all individuals.

PMID- 7589136
TI  - T lymphocytes from normal human peritoneum are phenotypically different from
      their counterparts in peripheral blood and CD3- lymphocyte subsets contain mRNA
      for the recombination activating gene RAG-1.
AB  - The surface antigens of peritoneal lymphocytes of healthy human individuals were
      studied. B lineage cells comprised 2.3% of the total peritoneal lymphocyte
      population. Although the majority of peritoneal cavity lymphocyte (PCL) T cells
      expressed alpha beta T cell receptor (TcR), up to 17% expressed gamma delta TcR.
      The majority of PCL exhibited markers of the thymus-dependent lineage (CD2+ CD3+
      TcR alpha beta + CD4+ or CD8 alpha + beta +) and surface antigens associated with
      memory and activation (CD45RO+ CD11a+ CD18+ CD49d+ HLA-DR). Up to 92% of both
      CD4+ and CD8+ T cells bore CDw60, thus characterizing the T cell subset
      containing helper activity for mitogen-driven B cell differentiation. The
      majority of PCL T cells were CD8+ and, in addition, up to 60% of this population
      expressed the homodimeric CD8 alpha + beta -. Messenger RNA for the recombination
      activating gene RAG-1 was examined in CD3- PCL depleted of CD19+ lineage cells.
      The PCL population which comprised cells containing RAG-1 mRNA transcripts was
      CD19-, surface IgM-, cytoplasmic IgM- and CD2- CD3- CD4- CD8- CD56-. However,
      this population was CD7+ (approx. 75%), and contained both CD7- CD34+ (up to 3%)
      and CD7- CD34+ (up to 3%) cells. These findings are compatible with the
      hypothesis that the adult human peritoneum provides a microenvironment capable of
      supporting a thymus-indenpendent differentiation of T lymphocytes.

PMID- 7589137
TI  - Quantitation of endogenous mouse mammary tumor virus superantigen expression by
      lymphocyte subsets.
AB  - Superantigens (SAg) encoded by endogenous mouse mammary tumor viruses (Mtv)
      interact with the V beta domain of the T cell receptor (TcR-V beta). Presentation
      of Mtv SAg can lead to stimulation and/or deletion of the reactive T cells, but
      little is known about the quantitative aspects of SAg presentation. Although
      monoclonal antibodies have been raised against Mtv SAg, they have not been useful
      in quantitating SAg protein, which is present in very low amounts in normal
      cells. Alternative attempts to quantitate Mtv SAg mRNA expression are complicated
      by the fact that Mtv transcription occurs from multiple loci and in different
      overlapping reading frames. In this report we describe a novel competitive
      polymerase chain reaction assay which allows the locus-specific quantitation of
      SAg expression at the mRNA level in lymphocyte subsets from mouse strains with
      multiple endogenous Mtv loci. In B cells as well as T cells (CD4+ or CD8+), Mtv-6
      SAg is expressed at the highest levels, followed by Mtv-7 SAg and (to a much
      lesser extent) Mtv-8,9. Consistent with functional Mtv-7 SAg presentation
      studies, we find that Mtv-7 SAg expression is higher in B cells than in CD8+ T
      cells and very low in the CD4+ subset. The overall hierarchy in Mtv SAg
      expression (i.e. Mtv-6 > Mtv-7 > Mtv 8,9) was also observed for mRNA isolated
      from neonatal thymus. Furthermore, the kinetics of intrathymic deletion of the
      corresponding TcR-V beta domains during ontogeny correlated with the levels of
      Mtv SAg expression. Collectively our data suggest that T cell responses to Mtv
      SAg are largely controlled by SAg expression levels on presenting cells.

PMID- 7589135
TI  - Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2
      deficient colitis.
AB  - Mice deficient in interleukin-2 production (IL-2null mice) develop colonic
      inflammation closely resembling ulcerative colitis in humans. Although this
      disease is marked by substantial infiltration of the colon by CD8+ and CD4+ T
      lymphocytes, no function has yet been assigned to these T cell subsets in the
      development of colitis in the IL-2null mouse. For the present study, we
      investigated the involvement of T lymphocytes in the onset of colitis in IL-2null
      mice, and examined the possible role played by cytotoxic T cells. Both lamina
      propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) of the colon of
      IL-2null mice were potently cytotoxic ex vivo in short-term redirected cytotoxic
      lymphocyte (CTL) assays. In contrast, colonic T cells of wild-type animals showed
      little or no constitutive cytotoxic T cell activity. Colonic CTL were detectable
      prior to the appearance of disease in IL-2null animals and CTL activity was
      confined to the TcR alpha beta, rather than to the TcR gamma delta IEL subset. IL
      2null animals crossed with major histocompatibility complex class I-deficient
      mice [IL-2null x beta 2 microglobulin (beta 2mnull) mice] also developed colitis,
      which appeared even earlier than in most IL-2null mice. These findings suggest
      that neither CD8+ IEL nor LPL were causal in the onset of colitis in IL-2null
      animals. In IL-2null x beta 2mnull mice, an ulcerative colitis-like disease was
      evident from histological studies and immunohistological staining which showed
      very large numbers of CD4+ lymphocytes within the intestinal mucosa. Significant
      ex vivo killing by CD4+ T cells was observed in IL-2null x beta 2null animals,
      although this required an extended incubation time compared to colonic CD8+ T
      cells. Peripheral as well as colonic CD4+ T cells in IL-2null and IL-2null x beta
      2mnull animals, were activated as judged by their cell surface phenotype
      (CD45RBlo, L-selectinlo and CD69+). In light of these findings, we propose that
      infiltrating CD4+, but not CD8+ T cells are central to the inflammation observed
      in the intestinal mucosa in IL-2null colitis.

PMID- 7589138
TI  - Cytotoxic T lymphocytes raised against a subdominant epitope offered as a
      synthetic peptide eradicate human papillomavirus type 16-induced tumors.
AB  - Previously, we have shown that immunization with human papillomavirus (HPV) type
      16-derived cytotoxic T lymphocyte (CTL) epitope E7 49-57 (RAHYNIVTF) renders
      C57BL/6 mice insensitive to tumors formed by HPV16-transformed cells. In this
      study, we provide evidence that E7 49-57 is expressed as a subdominant CTL
      epitope on HPV16-transformed C57BL/6 cells. Using acid peptide elution, it is
      shown that HPV16-transformed cells express another CTL epitope, besides E7 49-57,
      which appears to be dominant. We demonstrate that a CTL line raised against the
      subdominant CTL epitope, offered as synthetic peptide E7 49-57, eradicates
      established HPV16-induced tumors in mice. Our data show that synthetic peptide
      induced CTL can be applied successfully in vivo against (virus-induced) tumor,
      and emphasize that subdominant CTL epitopes are useful targets for immunotherapy.
      Furthermore, it is illustrated for the first time that HPV16-specific CTL
      interfere directly with HPV16-induced tumors.

PMID- 7589139
TI  - Transplantation tolerance induced by antigen pretreatment and depleting anti-CD4
      antibody depends on CD4+ T cell regulation during the induction phase of the
      response.
AB  - Adult mice pretreated with donor-specific transfusion and depleting anti-CD4
      antibody 28 days before transplant accept fully allogeneic heart grafts and
      become specifically tolerant without further treatment. The induction of
      tolerance in this model is not simply a function of CD4+ T cell ablation, but
      appears to depend on residual CD4+ T cells which escape depletion and engage
      donor alloantigen during a transient period of antibody blockade. To test the
      hypothesis that these CD4+ T cells might be responsible for regulating immune
      responses toward the graft, mice were reconstituted with naive recipient
      leukocytes at various times after pretreatment. Reconstitution either shortly
      after pretreatment or shortly after transplant had little effect on graft
      survival. However, when pretreated mice were given an additional dose of
      depleting anti-CD4 antibody at the time of transplant to target putative
      regulatory cells, naive leukocytes were able to cause acute graft rejection.
      These data suggest that in clinical transplantation specific T cell regulation
      might develop following pretreatment with antigen and non-depleting anti-CD4
      antibodies. Such an approach could provide donor-specific unresponsiveness prior
      to transplant without the risks associated with sustained CD4+ T cell depletion.

PMID- 7589134
TI  - Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte
      receptors: binding and signaling of MCP3 through shared as well as unique
      receptors on monocytes and neutrophils.
AB  - The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well
      as the capacity of MCP3 to desensitize leukocyte responses to other CC
      chemokines, suggested that MCP3 may interact with multiple CC chemokine
      receptors. The purpose of this study is to establish how MCP3 binds and activates
      monocytes and neutrophils. We show that human monocytes exhibit high-affinity
      binding for 125I-MCP3 with an estimated Kd of 1-3 nM and about 10,000 binding
      sites/cell. The binding of 125I-MCP3 to monocytes was progressively less well
      competed by CC chemokines macrophage inflammatory protein (MIP)1 alpha (Kd = 5-10
      nM), RANTES (Kd = 5-10 nM), MCP1 (monocyte chemoattractant and activating factor,
      or MCAF) (Kd = 60 nM) and MIP1 beta (Kd > 100 nM). On the other hand, unlabeled
      MCP3 displaced the binding of radiolabeled MIP1 alpha, RANTES, MCP1 and MIP1 beta
      as effectively as the isologous CC chemokines. In agreement with the binding
      data, pretreatment of monocytes with MCP3 completely desensitized the calcium
      flux in response to MIP1 alpha and RANTES. However, MIP1 alpha and RANTES failed
      to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially
      desensitized each other's effects on monocytes. These binding and cross
      desensitization results suggest that MCP3 binds and signals through other binding
      sites in addition to those shared with MIP1 alpha, RANTES and MCP1. The
      unidirectional competition for MIP1 beta binding and signaling by MCP3 suggests
      the existence of an as-yet unidentified site for MCP3 shared with MIP1 beta. The
      existence of another unique binding site(s) for MCP3 was further shown by the
      failure of any of the other CC chemokines to compete effectively for MCP3 binding
      on neutrophils. MCP3 in our study was also the only human CC chemokine that
      consistently chemoattracted neutrophils. These results suggest that MCP3 is a
      ligand that can bind and activate a broad range of target cells through receptors
      shared by other CC chemokines as well as its own receptor.

PMID- 7589140
TI  - T cell development and repertoire of mice expressing a single T cell receptor
      alpha chain.
AB  - We examined T cell development and T cell repertoire in transgenic mice
      expressing a single T cell receptor (TCR) alpha chain derived from the H-2Db
      lymphocytic choriomeningitis virus (LCMV)-specific cytolytic T lymphocyte (CTL)
      clone P14. To generate these alpha P14 mice, mice transgenic for the P14 TCR
      alpha chain were backcrossed to TCR alpha-deficient mice. Thymi from alpha P14
      mice exhibited a marked decrease of mature CD4+8- and CD8+4- single-positive
      thymocytes comparable to thymi from TCR alpha-deficient mice. Correspondingly,
      the number of peripheral T cells was reduced in the CD4 (tenfold) and in the CD8
      (twofold) subsets when compared to normal mice. T cells from alpha P14 mice
      generated a primary anti-LCMV CTL response when stimulated in vitro with LCMV in
      contrast to normal mice which require priming in vivo; elimination of LCMV in
      vivo was, however, not improved. Flow cytometric analysis of T cells with V beta
      specific antibodies showed a diverse endogenous TCR V beta repertoire. Functional
      analysis of the T cell repertoire, however, revealed a strongly reduced (30-fold)
      allogeneic and the absence of a vesicular stomatitis virus-specific CTL response
      and an impaired ability to provide T cell help for antibody isotype switching.
      Thus, T cell selection in the thymus was impaired and the T cell repertoire was
      limited in mice expressing only one type of TCR alpha chain.

PMID- 7589141
TI  - Polyinosinic acid: polycytidylic acid promotes T helper type 1-specific immune
      responses by stimulating macrophage production of interferon-alpha and
      interleukin-12.
AB  - The effects exerted on the development in vitro of Dermatophagoides pteronyssinus
      group I (Der p I)-specific T cell lines and T cell clones by addition of
      polyinosinic acid: polycytidylic acid (poly I:C) in lymphocyte bulk culture were
      examined. Der p I-specific T cell lines generated in presence of poly I:C
      exhibited reduced ability to produce interleukin (IL)-4 and IL-5 and developed
      into Der p I-specific CD4+ T cell clones showing a T helper (Th) type 0 or Th1,
      instead of Th0/Th2 cytokine profile. This effect was prevented by addition to
      lymphocyte bulk cultures of a mixture of antibodies specific for interferon (IFN)
      alpha and IL-12, whereas the addition of anti-IFN-alpha or anti-IL-12 antibody
      alone was uneffective. Poly I:C also showed the ability to stimulate the
      production of noticeable amounts of both IFN-alpha and IL-12 by human monocytes.
      Taken together, these data suggest that poly I:C is a Th1-inducing agent whose
      activity is mediated by its ability to stimulate the production of IFN-alpha and
      IL-12 by monocytes.

PMID- 7589143
TI  - Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on
      human peripheral blood dendritic cells.
AB  - Most of the immunosuppressive effects of interleukin-10 (IL-10) are related to
      functional inhibition of antigen-presenting cells (APC). Herein, we investigate
      the influence of recombinant (r)IL-10 on human dendritic cells (DC) purified from
      peripheral blood of healthy volunteers. First, we found that rIL-10 inhibited in
      a dose-dependent manner the proliferative responses as well as the production of
      IL-2 and interferon-gamma (IFN-gamma) in mixed lymphocyte reaction (MLR) between
      purified T cells and DC. This rIL-10 effect could be attributed to a direct
      effect on DC, as DC preincubated with rIL-10 were found to be deficient in the
      induction of alloreactive T cells even when anti-IL-10 neutralizing mAb was added
      at the time of MLR. Flow cytometric analysis indicated that rIL-10 did not modify
      the expression of ICAM-1 (CD54) and B7-1 (CD80), but decreased HLA-DR and B7-2
      (CD86) expression at the DC surface. We conclude that the inhibitory effect of
      rIL-10 on primary alloreactive T cell responses involves down-regulation of class
      II MHC and B7-2 expression at the DC surface.

PMID- 7589142
TI  - Epstein-Barr virus/C3d receptor (CR2, CD21) activated by its extracellular
      ligands regulates pp105 phosphorylation through two distinct pathways.
AB  - We previously demonstrated that human C3d or pep16, a 16-amino acid synthetic
      peptide derived from human C3d, induced in vivo and in vitro tyrosine
      phosphorylation of pp105, an intracellular component found only in human cells
      that express CR2 at their surface. To determine the contribution of CR2 molecules
      to this enzymatic regulation, we first analyzed whether activation of CR2 by
      other extracellular CR2 ligands could trigger such regulation in cell extracts.
      Subsequently, we used cell extracts of either CR2-positive cells depleted in CR2
      molecules by absorption with anti-CR2 antibodies or CR2-negative cells
      transfected with CR2 cDNA. We demonstrate here that pp105 phosphorylation was
      induced when CR2 was activated by C3d and pep16 as well as by gp350, the Epstein
      Barr virus capsid protein or OKB7, an anti-CR2 monoclonal antibody (mAb). HB5,
      another anti-CR2 mAb, which did not activate B lymphocytes through CR2, did not
      induce pp105 phosphorylation. Thus, C3d, pep16, gp350, and OKB7 presented similar
      properties in activating CR2 to trigger pp105 phosphorylation and in regulating B
      lymphocyte proliferation, while HB-5 had no effect on either assays. Furthermore,
      our data demonstrate that the presence of CR2 activated by its extracellular
      ligands regulates pp105 phosphorylation through two distinct pathways: one which
      also requires the presence of non-activated CD19, and one which is independent of
      CD19. The involvement of CD19 in the first pathway was not due to the formation
      of putative CR2-CD19 complexes. Both pathways were TAPA-1 independent. This is
      the first demonstration that activated CR2 molecules can play a regulatory role
      in enzymatic function, such as phosphorylation, despite the absence of CD19 and
      TAPA-1.

PMID- 7589144
TI  - Physical association and functional relationship between protein kinase C zeta
      and the actin cytoskeleton.
AB  - Protein kinase C (PKC) was initially identified as a serine/threonine protein
      kinase dependent on calcium and phospholipids and shown to be involved in
      intracellular signaling pathways. PKC isoforms have been classified into four
      groups: Ca(2+)-dependent conventional PKC alpha, beta I, beta II, gamma; Ca(2+)
      independent, novel PKC delta, epsilon, eta, phi; atypical PKC zeta, lambda, iota
      which are not activated by Ca2+ or diacylglycerol, and the recently discovered
      PKCmu. We reported that activation of the zeta PKC isoform is an important step
      in interleukin-2 (IL-2)-mediated proliferation (Gomez, J., Pitton, C., Garcia,
      A., Martinez, A., Silva, A. and Rebollo, A., Exp. Cell Res. 1995. 218: 105.).
      zeta PKC is also required for mitogenic activation of fibroblasts and for the
      maturation pathway activated by insulin and Ras. Contradictory results have been
      reported regarding the subcellular redistribution of zeta PKC upon activation. We
      report here, using confocal microscopy, that IL-2 induces expression,
      translocation and association of zeta PKC to a structure coincident with the
      actin cytoskeleton. Furthermore, we show that zeta PKC has a role in maintaining
      the integrity of the actin cytoskeletal structure in IL-2-stimulated cells. On
      the contrary, zeta PKC is not involved in the actin cytoskeleton organization
      when cells are maintained in IL-4, confirming our previous results showing that
      IL-4-induced signal transduction is PKC independent.

PMID- 7589145
TI  - Down-modulation of CD4+ T helper type 2 and type 0 cells by T helper type 1 cells
      via Fas/Fas-ligand interaction.
AB  - Fas was recently demonstrated to be the major target molecule engaged by CD4+
      cytolytic T lymphocytes (CTL). We examined Fas expression on various cloned T
      cell subpopulations and their susceptibility to lysis by CD4+ or CD8+ CTL. A
      reciprocal relationship in Fas and Fas-ligand expression was observed in CD4+ T
      helper (Th)1- and Th2-type clones, and Fas mRNA was predominantly detected in Th2
      clones, whereas Fas-ligand mRNA was principally found in Th1 clones. The two Th0
      clones tested expressed both Fas and Fas-ligand, but only one exhibited cytolytic
      activity, whereas both were sensitive to CD4-mediated lysis. A functional
      consequence of the inverse Fas-Fas-ligand expression pattern was that Th2 and Th0
      cells were sensitive to lysis by both Th1 CD4+ CTL and a CD8+ CTL clone in a Fas
      dependent manner. These results suggest that cytolytic CD4+ Th1 cells may play an
      immunomodulatory role, regulating a Th2/Th0 response by Fas-mediated lysis.

PMID- 7589146
TI  - Expression of a gastric autoantigen in pancreatic islets results in non
      destructive insulitis after neonatal thymectomy.
AB  - Autoimmune gastritis, induced by day-3 thymectomy of BALB/c mice, is a
      destructive CD4+ T cell-mediated disease characterized by leukocyte infiltrates
      in the gastric mucosa, loss of parietal and chief cells and anti-gastric H/K
      ATPase autoantibodies. Our previous studies have indicated that a T cell response
      to the H/K ATPase beta subunit is required for the onset of autoimmune gastritis
      (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J.
      Exp. Med. 1993. 178: 419). To determine whether a response to the beta subunit
      autoantigen is alone sufficient to induce autoimmunity, or whether other tissue
      specific factors are required, we have generated transgenic mice expressing the
      gastric H/K ATPase beta subunit in beta islet cells of the pancreas (RIP-H/K
      beta). RIP-H/K beta mice developed autoimmune gastritis and insulitis after day-3
      thymectomy. Significantly, insulitis, observed as a peri-islet infiltrate, was
      only detected in thymectomized mice with autoimmune gastritis. There was no
      apparent immune destruction of the pancreas as insulitis did not progress to
      invasion of the islets or diabetes. Double transgenic mice, expressing the
      gastric H/K ATPase beta subunit in the thymus and in the pancreas, were protected
      from both gastritis and insulitis after day-3 thymectomy. Therefore, insulitis in
      the RIP-H/K beta mice appears to be dependent on a T cell response to the H/K
      ATPase beta subunit. This is the first example where an organ-specific initiating
      autoantigen has been expressed in another peripheral tissue. Autoimmune
      destruction in the stomach, but not the pancreas, indicates that tissue-specific
      factors play a fundamental role in the development of organ-specific
      autoimmunity.

PMID- 7589150
TI  - Differential expression of the T cell receptor/CD3 genes and their lymphoid
      specific transcription factor genes in murine T cell x fibroblast and T cell x B
      cell hybrids.
AB  - We generated cell hybrids between mouse T cell lymphoma EL4 cells and mouse
      fibroblast B82 cells (BELIII and BELIV) to examine the expression of T cell
      receptor (TcR)/CD3 genes and their lymphoid-specific transcription factor genes,
      which are normally detected in EL4 cells. In BELIII and BELIV, expression of the
      TcR alpha, TcR beta and CD3 delta genes was extinguished, whereas expression of
      the CD3 epsilon gene was still detected. Expression of the (lymphoid enhancer
      binding factor 1) LEF-1 gene was extinguished and that of the GATA-3 gene was
      hardly detected in BELIII and BELIV. Ets-1 gene expression, observed not only in
      EL4 cells but also in B82 cells, was considerably reduced in BELIII and BELIV. A
      much higher level of PEBP2 alpha A gene expression was observed in B82 cells than
      in EL4 cells and was preserved in BELIII and BELIV. To examine whether reduced
      expression of these genes is also found in T cell x B cell hybrids, we generated
      an additional cell hybrid between EL4 cells and mouse plasmacytoma S194 cells
      (SELIII). Marked differences were observed in the expression of the TcR alpha,
      CD3 delta, LEF-1 and PEBP2 alpha A genes in BEL and SEL hybrids. Expression of
      the TcR alpha, CD3 delta and LEF-1 genes, which was extinguished in BELIII and
      BELIV, was detected in SELIII. PEBP2 alpha A gene expression, not detected in
      S194 cells, was considerably reduced in SELIII. Almost the sum of the chromosomes
      from the parental cells were retained by, and the presence of every gene was
      proven, in each cell hybrid. These results suggest that suppression of the
      expression of lymphoid-specific transcription factor genes may precede that of
      the TcR/CD3 genes in the cell hybrids, and that the presence of a different trans
      acting negative regulatory mechanism(s) suppresses the expression of T cell
      specific genes in fibroblasts and B cells.

PMID- 7589148
TI  - Monocyte activation: rapid induction of alpha 1/beta 1 (VLA-1) integrin
      expression by lipopolysaccharide and interferon-gamma.
AB  - Monocytes play a key role in inflammation, tissue injury and remodelling and
      wound healing, and most monocyte effector functions are dependent on adhesive
      interactions. We have analyzed the changes in the pattern of beta 1 integrin
      expression that take place during monocyte activation and demonstrated that
      lipopolysaccharide (LPS) and interferon (IFN)-gamma specifically induce the
      expression of the alpha 1/beta 1 integrin, which was detectable on the monocyte
      membrane as early as 12 h after monocyte activation. The up-regulated alpha
      1/beta 1 expression was not dependent on monocyte adherence to solid surfaces,
      and Northern blot analysis revealed that LPS and IFN-gamma induce the alpha 1
      mRNA de novo. Monocyte deactivating cytokines such as interleukin (IL)-4 or IL
      10, could only minimally inhibit the LPS- or IFN-gamma mediated up-regulation of
      alpha 1/beta 1, suggesting that cytokine release subsequent to monocyte
      activation does not play a major role in the integrin induction. Interestingly,
      the LPS-induced expression of alpha 1/beta 1 was found to be dependent on the
      redox state of the cell, since it was inhibited by antioxidants which also
      altered the morphological changes that take place during monocyte culture in
      vitro. The rapid induction of alpha 1 in LPS-activated monocytes suggests that
      alpha 1/beta 1 might be involved not only in monocyte/extracellular matrix
      interactions during inflammatory reactions, but also in contributing to further
      monocyte activation and cytokine production during septic shock syndrome.

PMID- 7589149
TI  - Evidence that productive rearrangements of TCR gamma genes influence the
      commitment of progenitor cells to differentiate into alpha beta or gamma delta T
      cells.
AB  - Two models have been considered to account for the differentiation of gamma delta
      and alpha beta T cells from a common hematopoietic progenitor cell. In one model,
      progenitor cells commit to a lineage before T cell receptor (TCR) rearrangement
      occurs. In the other model, progenitor cells first undergo rearrangement of TCR
      gamma, delta, or both genes, and cells that succeed in generating a functional
      receptor commit to the gamma delta lineage, while those that do not proceed to
      attempt complete beta and subsequently alpha gene rearrangements. A prediction of
      the latter model is that TCR gamma rearrangements present in alpha beta T cells
      will be nonproductive. We tested this hypothesis by examining V gamma 2-J gamma
      1C gamma 1 rearrangements, which are commonly found in alpha beta T cells. The
      results indicate that V gamma 2-J gamma 1C gamma 1 rearrangements in purified
      alpha beta T cell populations are almost all nonproductive. The low frequency of
      productive rearrangements of V gamma 2 in alpha beta T cells is apparently not
      due to a property of the rearrangement machinery, because a transgenic
      rearrangement substrate, in which the V gamma 2 gene harbored a frame-shift
      mutation that prevents expression at the protein level, was often rearranged in a
      productive configuration in alpha beta T cells. The results suggest that
      progenitor cells which undergo productive rearrangement of their endogenous V
      gamma 2 gene are selectively excluded from the alpha beta T cell lineage.

PMID- 7589147
TI  - Exogenous human immunodeficiency virus type-1 Tat protein selectively stimulates
      a phosphatidylinositol-specific phospholipase C nuclear pathway in the Jurkat T
      cell line.
AB  - We investigated the effect of extracellular Tat protein of human immunodeficiency
      virus-type 1 (HIV-1) on the phosphatidylinositol (PI) cycle, which represents a
      major signal transduction pathway in lymphoid cells. Recombinant Tat, recombinant
      HIV-1 p24 and cross-linked anti-CD3 monoclonal antibody (mAb) were added in
      culture for 1-60 min to Jurkat lymphoblastoid CD4+ T cells. The stimulation of T
      cell receptor by cross-linked anti-CD3 mAb resulted in a rapid increase of the
      phosphatidylinositol-specific phospholipase C (PI-PLC) activity in whole cell
      lysates. On the other hand, Tat protein, either alone or in combination with anti
      CD3 mAb, showed little effect on the PI turnover of whole cell extracts. Tat,
      however, selectively stimulated a nuclear-specific PI-PLC with a peak of activity
      after 30 min from the addition in culture to Jurkat cells. Interestingly, this
      time corresponded to that required for the uptake and nuclear localization of
      recombinant Tat protein, as demonstrated by electron microscope
      immunocytochemistry experiments with anti-Tat mAb. Moreover, exogenous Tat
      reached the nucleus of Jurkat cells in a bioactive form, as shown in a HIV-1 long
      terminal repeat-chloramphenicol acetyl transferase transactivation assay. The
      specific increase of a nuclear PI-PLC activity was further demonstrated by the
      ability of Tat to stimulate PI turnover also when added directly to isolated
      nuclei. As a whole, these data demonstrate that Tat selectively stimulates a
      nuclear polyphosphoinositide hydrolysis, which appears to be independent of the
      cellular PI turnover. The relevance of these findings for a better understanding
      of the biological functions of extracellular Tat is discussed.

PMID- 7589151
TI  - Polymorphonuclear granulocytes enhance lipopolysaccharide-induced soluble p75
      tumor necrosis factor receptor release from mononuclear cells.
AB  - Lipopolysaccharide (LPS), a part of the Gram-negative bacteria cell wall, is a
      potent inducer of tumor necrosis factor (TNF). TNF is an important mediator in
      Gram-negative infections such as meningococcal septic shock, but its harmful
      action can be prevented by the natural occurring soluble (s) TNF receptors
      (sTNFR) sp55 and sp75. In this study, the effect of LPS on release of sTNFR was
      investigated. First, we found a selective increase in human whole-blood sp75 TNFR
      levels following LPS stimulation, accompanied by no increase in sp55. Separating
      the different blood cell populations, mononuclear cells (PBMC) selectively
      released sp75 upon LPS stimulation, while LPS induced a minor increase in sp75
      release from polymorphonuclear granulocytes. Interestingly, in co-cultures of
      PBMC and granulocytes, the release of LPS-induced sp75 TNFR was enhanced. Second,
      adherent monocytes were also found to selectively release sp75 TNFR upon LPS
      stimulation, where Neisseria meningitidis LPS was found to be 100-1000 times more
      potent in inducing sp75 release than Escherichia coli LPS. Using flow cytometry,
      the monocyte membrane distribution of both TNFR were found to be increased after
      LPS stimulation. Third, human umbilical vein endothelial cells selectively
      released sp55 TNFR after stimulation with LPS. We conclude that mononuclear and
      endothelial cells might be the main sources of soluble p75 and p55 TNFR,
      respectively, observed in Gram-negative sepsis, although these receptors are
      released in vivo more rapidly than they are in vitro.

PMID- 7589152
TI  - CD4/major histocompatibility complex class II interaction analyzed with CD4- and
      lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins.
AB  - We analyzed CD4 major histocompatibility complex (MHC) class II interactions with
      CD4 and lymphocyte activation gene (LAG)-3 recombinant fusion proteins termed
      CD4Ig and LAG-3Ig. CD4Ig bound MHC class II molecules expressed on the cell
      surface only when used in the micromolar range. This weak CD4Ig binding was
      specific, since it was inhibited by anti-CD4 and anti-MHC class II mAb. LAG-3Ig
      bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37 degrees
      C). Using LAG-3Ig as a competitor in a CD4/MHC class II-dependent cellular
      adhesion assay, we showed that this recombinant molecule was able to block
      CD4/MHC class II interaction. In contrast, no inhibition was observed in a
      CD4/MHC class II-dependent T cell cytotoxicity assay. Together, these results
      suggest that co-engagement of the TcR with CD4 alters the CD4/MHC class II
      molecular interaction to become insensitive to LAG-3Ig competition.

PMID- 7589154
TI  - Gestational changes in oxytocin- and endothelin-1-induced contractility of
      pregnant rat myometrium.
AB  - The mechanical effects of KCl, oxytocin and endothelin-1 on pregnant rat
      myometrium were examined using intact strips and beta-escin-treated skinned
      strips. Myometrial tissues from delivering rats were more sensitive to 10.7 mM K+
      compared to mid and late gestation. Maximum contractions induced by K+ were
      obtained at concentrations of 118 mM at mid and late gestation and during
      delivery. The maximum amplitude of contractions induced by oxytocin and
      endothelin-1 compared to the 118 mM K(+)-induced contraction increased during the
      progress of gestation. Maximum contractions induced by oxytocin and endothelin-1
      were greater than those induced by 118 mM K+ at delivery, and maximum
      contractions by oxytocin were larger than those by endothelin-1 during delivery.
      In 10 microM nifedipine and Ca(2+)-free (containing 2 mM EGTA) solutions, 118 mM
      K+ contractions were completely abolished; however, both oxytocin and endothelin
      1 produced contractions. In Ca(2+)-free solutions, contractions by oxytocin were
      larger than those by endothelin-1. In skinned myometrial strips, guanosine 5'-O
      thiotriphosphate (GTP, 1 microM-1 mM), guanosine 5'-O-(gamma-thiotriphosphate)
      (GTP gamma S, 0.1-100 microM) and oxytocin (1 nM-0.1 microM) with 10 microM GTP,
      but not endothelin-1 with 10 microM GTP increased Ca2+ sensitivity of contractile
      force.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589153
TI  - Human naive CD4 T cells produce interleukin-4 at priming and acquire a Th2
      phenotype upon repetitive stimulations in neutral conditions.
AB  - The maturation of naive CD4 T cells into interleukin (IL)-4-producing effectors
      was shown to require the presence of IL-4 at priming, the cellular origin of
      which remains unclear. We demonstrate here that naive T cells themselves release
      IL-4 at very low levels that are nevertheless sufficient to promote their
      development into Th2-like cells. This conclusion is based on three observations:
      (1) highly purified human naive CD4 T cells, of neonatal or adult origin, develop
      into Th2 effectors upon repetitive cycles of stimulation with anti-CD3 monoclonal
      antibody (mAb) cross-linked to CD32-B7 transfected L fibroblasts followed by IL-2
      expansion; (2) IL-4 protein is readily detectable in the concentrated supernatant
      fluids of priming cultures performed in the presence of anti-IL-4 receptor mAb;
      and (3) addition of anti-IL-4 or anti-IL-4 receptor mAb at priming markedly
      inhibits the acquisition of IL-4- and IL-5-producing capacity while enhancing
      that of interferon-gamma.

PMID- 7589155
TI  - Role of muscarinic M2 and M3 receptors in guinea-pig trachea: effects of receptor
      alkylation.
AB  - Muscarinic M2 receptors account for more than half the muscarinic receptor
      population in smooth muscles of a number of species and yet it is the smaller M3
      receptor population that mediates contraction of many of these tissues. The role
      of the majority of M2 receptors in the control of smooth muscle tone is unclear.
      In guinea-pig ileal smooth muscle, an indirect contractile role (re-contraction)
      for M2 receptors has been demonstrated in tissues subjected to M3 receptor
      alkylation and stimulation of adenylyl cyclase. The present studies have employed
      the technique of irreversible receptor alkylation in order to investigate the
      role of muscarinic M2 and M3 receptors in the control of guinea-pig tracheal
      smooth muscle tone. Experiments were performed to determine (i) whether an
      indirect contractile role for M2 receptors can be demonstrated in tracheal smooth
      muscle as described for ileum, and (ii) whether stimulation of M2 receptors can
      inhibit isoprenaline-induced relaxations of histamine pre-contracted trachea
      after selective M3 receptor alkylation. Our results suggest (i) that there is no
      evidence of M2 receptor-mediated re-contraction of tracheal smooth muscle after
      M3 receptor alkylation and stimulation of adenylyl cyclase, but (ii) that
      activation of M2 receptors, after M3 receptor alkylation, has a small inhibitory
      effect on relaxant responses to isoprenaline in guinea-pig tracheal smooth
      muscle. Therefore, it appears that the major role of postjunctional muscarinic M2
      receptors in guinea-pig trachea remains to be determined.

PMID- 7589156
TI  - Role of endogenous gastrin in gastroprotection.
AB  - Gastrin has a potent influence on gastric acid secretion and mucosal growth but
      its role in mucosal integrity has been little studied. This study investigated in
      rats whether gastrin protects the gastric mucosa against the damage by 100%
      ethanol and what are the possible mechanisms of this protection. Exogenous
      gastrin-17 (0.6-5.0 pmol/kg) injected subcutaneously (s.c.) reduced dose
      dependently ethanol-induced mucosal damage and the dose decreasing the ethanol
      lesions by 50% was about 1.8 pmol/kg. The protection afforded by gastrin-17 was
      accompanied by a dose-dependent increase in gastric blood flow and these effects
      were almost completely abolished by the pretreatment with specific CCKB (L
      365,260) but not CCKA receptor antagonist (loxiglumide). Endogenous gastrin
      released by intragastric (i.g.) peptone meal or s.c. injection of gastrin
      releasing peptide prevented the formation of acute ethanol-induced lesions and
      these effects were also abolished by the pretreatment with L-365,260 but not by
      loxiglumide. The inhibition of nitric oxide (NO) synthase, by NG-nitro-L-arginine
      methyl ester almost completely eliminated both the protective and hyperemic
      effects of gastrin-17 and the addition of L-arginine (but not D-arginine) to NG
      nitro-L-arginine-methyl ester restored, in part, these effects of gastrin-17.
      Deactivation of sensory nerves with capsaicin did not influence the protective or
      hyperemic effects of gastrin-17. We conclude that both exogenous and endogenous
      gastrin exert its protective activity against ethanol damage of gastric mucosa
      and this effect is mediated through the interaction with specific CCKB receptors
      and arginine-NO pathway, but does not involve sensory nerves.

PMID- 7589158
TI  - Intracellular Ca2+ depletion and Ca2+ channel blockers increase renal kallikrein
      secretion.
AB  - This study examined the effect of various manipulations of intracellular Ca2+ on
      kallikrein release by renal cortical slices. Increasing the extracellular Ca2+
      concentration and the addition of Ca2+ ionophore A23187 was without effect on
      kallikrein release. In contrast, kallikrein release was enhanced by the addition
      of either extracellular or intracellular Ca2+ chelators in Ca(2+)-free medium and
      by two Ca2+ channel blockers, verapamil and nifedipine. Kallikrein release was
      also highly enhanced in depolarising medium (10-100 mM potassium chloride). Since
      potassium chloride induced a dose-related increase in free cytosolic Ca2+ which
      was abolished by nifedipine whereas the stimulation of kallikrein secretion
      persisted, a direct stimulating effect of potassium, at least at sub
      physiological concentration, is suggested. Similarily, inhibition of either
      sodium/potassium-ATPase and Ca2+ ATPase by ouabain and vanadium respectively, was
      also without effect on kallikrein secretion. Taken together, these results
      indicate that intracellular Ca2+ depletion, Ca2+ channel blockers and high
      extracellular K+ concentrations, acting through different mechanisms, are
      effective stimuli for kallikrein secretion, at least in the isolated renal
      cortical slice.

PMID- 7589157
TI  - Stereospecific transduction of behavioral effects via diazepam-insensitive GABAA
      receptors.
AB  - Previous studies reported a positive correlation between ligand affinities at
      diazepam-insensitive GABAA receptors and substitution for the discriminative
      stimulus effects of the benzodiazepine receptor antagonist, flumazenil, in
      pigeons. In the present experiments, bretazenil and Ro 14-5974 (ethyl-(S)
      11,12,13,13 a-tetrahydro-9-oxo-9H-imidazo[1,5-a]-pyrrolo-[2,1-c]
      [1,4]benzodiazepine-1-carboxylate) partially substituted for, and blocked the
      discriminative stimulus effects of midazolam, congruent with their actions at
      diazepam-sensitive GABAA receptors in vitro. In addition, bretazenil and Ro 14
      5974, but not their R-enantiomers, had high affinity for diazepam-insensitive
      receptors and fully substituted for the discriminative stimulus effects of
      flumazenil. The R-enantiomers of these compounds had low affinity (Ki > 1 microM)
      for diazepam-sensitive and diazepam-insensitive receptors, and did not share
      discriminative stimulus effects with flumazenil or midazolam. Ro 19-0528 (7
      chloro-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4,5-dihydro-5-met hyl-6H-
      imidazo[1,5-a][1,4]benzodiazepin-6-one), a structurally related compound with
      full agonist actions at diazepam-sensitive GABAA receptors, had high diazepam
      insensitive receptor affinity (Ki = 96 nM) and partially substituted for the
      discriminative stimulus effects of flumazenil. These results are consistent with
      stereospecific mediation of the discriminative stimulus effects of flumazenil
      through high affinity binding to diazepam-insensitive receptors in pigeons.

PMID- 7589160
TI  - Labeling of neuropeptide Y receptors in SK-N-MC cells using the novel, nonpeptide
      Y1 receptor-selective antagonist [3H]BIBP3226.
AB  - The binding of tritium-labelled BIBP3226, N2-(diphenylacetyl)-N-[(4-hydroxy
      phenyl)methyl]-D-arginine amide, to human neuroblastoma SK-N-MC cells was
      investigated. [3H]BIBP3226 reversibly binds to neuropeptide Y receptors of the Y1
      subtype expressed in SK-N-MC cells with a KD of 2.1 +/- 0.3 nM (mean +/- S.E.M.,
      n = 3) and a Bmax of 58,400 +/- 1100 sites/cell. Non-specific binding did not
      exceed 30% of the total radioactivity bound at KD. In competition experiments
      [3H]BIBP3226 is concentration-dependently displaced by neuropeptide Y and its
      peptide analogues with an affinity pattern neuropeptide Y = [Leu31,
      Pro34]neuropeptide Y >> neuropeptide Y-(18-36). This rank order of potencies is
      consistent with the interaction of [3H]BIBP3226 with neuropeptide Y receptors of
      the Y1 subtype. Therefore, [3H]BIBP3226 can be used as selective ligand to study
      neuropeptide Y Y1 receptors.

PMID- 7589161
TI  - Relative affinities of dopaminergic drugs at dopamine D2 and D3 receptors.
AB  - Quantitative autoradiography was used to evaluate the pharmacological profile of
      dopamine D2-like receptors labeled by [125I]iodosulpiride. Caudate/putamen, a
      brain region associated primarily with dopamine D2 receptor mRNA, was used as a
      prototypical D2 tissue; cerebellar lobule X (D3 mRNA associated), as a D3 tissue.
      7-OH-DPAT ((+/-)-2-dipropylamino-7-hydroxy-1,2,3,4- tetrahydronaphthalene)
      exhibited selectively for cerebellar receptors (24-fold), followed by quinpirole
      (6-fold). Haloperidol and domperidone were 4- and 18-fold more potent at striatal
      receptors, respectively. These data are in close agreement with that derived from
      dopamine D2 and D3 receptor-expressing cell lines.

PMID- 7589159
TI  - Chronic intracerebroventricular administration of morphine down-regulates spinal
      adenosine A1 receptors in rats.
AB  - Previous studies from our laboratory have shown that systemic chronic morphine
      treatment causes down-regulation of spinal adenosine A1 receptors in rats. In
      this study, we further investigated whether supraspinal morphine treatment causes
      this effect. Adult male Sprague-Dawley rats were rendered tolerant to morphine by
      multiple intracerebroventricular (i.c.v.) injections for 2 or 4 days. Adenosine
      A1 receptor binding activities were measured with [3H]cyclohexyladenosine in the
      spinal cord and midbrain. A significant decrease in [3H]cyclohexyladenosine
      binding was found in the spinal cord but not in the midbrain region after 2 or 4
      days of chronic i.c.v. morphine treatment. A decrease in the number of binding
      sites (Bmax) with no change in the affinity (Kd) of the ligand for the adenosine
      A1 receptor was observed. These results suggest that supraspinal morphine
      administration could cause the down-regulation of spinal adenosine A1 receptors
      and this may play a role in the mechanism of morphine tolerance.

PMID- 7589162
TI  - Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is
      stereospecific.
AB  - The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral
      high performance liquid chromatography. The (+)-isomer showed high affinity in
      vitro (Ki = 0.97 +/- 0.48 nM) for the vesicular monoamine transporter (VMAT2) in
      rat brain striatum, whereas the (-)-isomer was inactive (Ki = 2.2 +/- 0.3
      microM). Each isomer was then synthesized in carbon-11 labeled form, and regional
      brain biodistributions in mice determined after intravenous injection. Only (+)
      alpha-dihydrotetrabenazine showed selective and specific accumulations in regions
      of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be
      blocked by coinjection of unlabeled tetrabenazine. Binding of alpha
      dihydrotetrabenazine to the vesicular monoamine transporter is thus
      stereospecific.

PMID- 7589164
TI  - CB-64D and CB-184: ligands with high sigma 2 receptor affinity and subtype
      selectivity.
AB  - Four members of a novel class of sigma (sigma) ligands were investigated for
      sigma subtype selectivity. (-)-1S,5S- and (+)-1R,5R-(E)-8-Benzylidene-5-(3
      hydroxyphenyl)-2-methylmorphan-7- one (CB-64L and CB-64D, respectively) exhibited
      sigma 1 Ki = 10.5 nM and 3063 nM; sigma 2 Ki = 154 nM and 16.5 nM, respectively.
      The corresponding 3,4-dichloro derivatives, (-)-1S,5S- and (+)-1R,5R-(E)-8-(3,4
      dichlorobenzylidene)-5-(3-hydroxyphenyl)-2-++ +methylmorphan-7 - one (CB-182 and
      CB-184, respectively) were also examined. CB-182 ((-)-isomer) showed sigma 1 and
      sigma 2 Ki = 27.3 nM and 35.5 nM, respectively, whereas CB-184 ((+)-isomer)
      exhibited sigma 1 and sigma 2 Ki = 7436 nM and 13.4 nM, respectively. Thus, the
      two sigma subtypes showed opposite enantioselectivity for these compounds, with (
      ) > (+) at sigma 1 and (+) > (-) at sigma 2. Importantly, CB-64D and CB-184
      showed high sigma 2 affinity and, respectively, 185-fold and 554-fold selectivity
      for sigma 2 receptors over sigma 1. While high sigma 2 selectivity relative to
      sigma 1 was achieved with these compounds, they both exhibited high affinity at
      mu (mu) opioid receptors (Ki = 37.6 nM and 4.5 nM, respectively). Despite this,
      CB-64D and CB-184 will be useful tools for further characterization of sigma 2
      receptors.

PMID- 7589166
TI  - A study of prostacyclin mimetics distinguishes neuronal from neutrophil IP
      receptors.
AB  - The prostacyclin mimetics BMY 45778 (3-[4-(4,5-diphenyl-2-oxazolyl)-5
      oxazolyl]phenoxy]acetic acid), BMY 42393 (2-[3-[2-(4,5-diphenyl-2
      oxazolyl)ethyl]phenoxy]acetic acid) and EP 185 (rac 5-endo-(6'-carboxyhex-2'Z
      enyl)-6-exo-(p-methoxyphenyl- phenyl-methylazino)-bicyclo[2.2.2]oct-2-ene)
      inhibited rat neutrophil aggregation stimulated by N-formyl-methionyl-leucyl
      phenylalanine (IC50 = 20, 462, and 1195 nM respectively). In contrast only BMY
      45778 (1-10 microM) produced any significant inhibition (10-20%) of the
      spontaneous activity of rat colon. BMY 45778 (10 microM) also attenuated the
      inhibitory effect of the prostacyclin analogue cicaprost on rat colon, whereas
      BMY 42393 and EP 185 did not. BMY 45778 appears to be a low affinity partial
      agonist at prostacyclin receptors on rat colon and its low potency in rat colon
      compared with rat neutrophils suggests the presence of a different prostacyclin
      receptor located on enteric neurones.

PMID- 7589163
TI  - Furosemide inhibits bradykinin-induced contraction of human bronchi: role of
      thromboxane A2 receptor antagonism.
AB  - Bradykinin contracts human isolated small bronchi through prostanoid release and
      subsequent TP receptor stimulation. Furosemide 10(-4) to 10(-3) M concentration
      dependently inhibited bradykinin- and the stable TP receptor agonist U-46619
      induced contraction of human isolated small airways. The inhibitory effect of
      furosemide on U-46619-induced contraction involves competitive antagonism at TP
      receptors. Such an inhibition of TP receptors could a least partly explain the
      inhibitory effect of furosemide on bradykinin-induced contraction, and could be
      one of the mechanisms of the protective effect of furosemide in asthma.

PMID- 7589165
TI  - Binding of [3H]cirazoline to an imidazoline site in rat brain and kidney
      membranes.
AB  - Two classes of high-affinity sites for [3H]cirazoline were characterized in rat
      brain and kidney membranes. In both tissues, the binding parameters for the high-
      and low-affinity sites are similar with Bmax values of approximately 50 fmol/mg
      protein, Kd approximately 0.6 nM and Bmax approximately 470 fmol/mg protein, Kd
      approximately 11 nM respectively. Inhibition studies of [3H]cirazoline binding to
      the lower affinity site revealed that only guanidinium or imidazoline derivatives
      compete with the specific binding of this radioligand. Our results suggest that
      [3H]cirazoline could be used as a novel ligand to label the non-adrenergic
      imidazoline-preferring sites.

PMID- 7589168
TI  - Cisplatin acutely reduces 5-hydroxytryptamine-induced vagal depolarization in the
      rat: protective action of dexamethasone.
AB  - The effect of the anti-cancer cytotoxic drug cisplatin on KCl and 5
      hydroxytryptamine (5-HT)-induced depolarization in the rat isolated cervical
      vagus nerve was investigated using the 'grease gap' extracellular recording
      technique. KCl (10 mM) perfused onto the isolated nerve previously incubated for
      2 h in 10 microM cisplatin initiated a d.c. potential of 1.06 +/- 0.09 mV
      compared to a potential of 1.29 +/- 0.13 mV in control nerves. Perfusion with 5
      microM 5-HT produced a markedly reduced depolarization (0.23 +/- 0.02 mV) in
      cisplatin-treated nerves compared with control nerves (0.42 +/- 0.04 mV, P =
      0.005). This effect was enhanced when 5-HT was reapplied 30 min later (0.19 +/-
      0.02 mV in cisplatin-treated compared with 0.42 +/- 0.03 mV in controls, P <
      0.0001). The inhibitory effect of cisplatin on 5-HT-induced depolarization was
      found to be significantly (P = 0.004) reduced by the addition of dexamethasone
      (10 microM) to the incubation buffer (0.34 +/- 0.04 mV). These results are
      discussed in the light of the emetic and neurotoxic effects of cisplatin and the
      protective effects of dexamethasone.

PMID- 7589167
TI  - Gonadal steroid hormones upregulate medial preoptic mu-opioid receptors in the
      rat.
AB  - The density of mu-opioid receptors is dependent upon the levels of gonadal
      steroid hormones in the medial preoptic area of ovariectomized female rats.
      Because the region containing these cyclical mu-opioid receptors is relatively
      small, autoradiographic analysis of the binding of a saturating concentration of
      mu-selective radioligand was used to determine whether hormone treatment affects
      maximal binding capacity of these receptors. The results reveal that gonadal
      steroid hormones upregulate mu-opioid receptor binding capacity specifically in
      the medial preoptic area 27 h later, without affecting binding in adjacent brain
      regions. This suggests that hormones induce a functional increase of medial
      preoptic area mu-opioid receptors which could serve to regulate reproductive
      activities.

PMID- 7589171
TI  - Tyrosine kinase inhibitors regulate serotonin uptake in platelets.
AB  - Uptake of tritiated serotonin into human platelets was found to be rapidly
      inhibited by the tyrosine kinase inhibitors, genistein and methyl 2,5
      dihydroxycinnamate. Binding studies indicated that uptake inhibition did not
      correlate with direct binding of these inhibitors to the transporter. Chelation
      of mobilizable intracellular Ca2+ did not inhibit the effects of genistein on
      uptake. These results suggest a more direct, non-Ca2+ mediated effect of tyrosine
      kinase inhibitors on uptake.

PMID- 7589170
TI  - Inhibition of protein kinase C, but not of protein kinase A, blocks the
      development of acute antinociceptive tolerance to an intrathecally administered
      mu-opioid receptor agonist in the mouse.
AB  - A specific protein kinase C inhibitor, calphostin C, which injected alone had no
      effect on the antinociception induced by intrathecal (i.t.) administration of a
      selective mu-opioid receptor agonist, [D-Ala2,NMePhe4,Gly(ol)5]enkephalin
      (DAMGO), dose-dependently attenuated the development of acute tolerance to the
      i.t. DAMGO-induced antinociception in male ICR mice. On the other hand, a
      selective protein kinase A inhibitor, KT5720, did not have any effect on the
      development of acute tolerance to DAMGO antinociception. These findings suggest
      that protein kinase C, but not protein kinase A, plays an important role in the
      development of acute tolerance to the mu-opioid receptor agonist-induced
      antinociception.

PMID- 7589169
TI  - Novel antagonist implicates the CB1 cannabinoid receptor in the hypotensive
      action of anandamide.
AB  - In anaesthetised rats, the endogenous cannabinoid anandamide has potent
      cardiovascular effects that include a brief pressor effect and a more prolonged
      depressor response. The depressor response is attenuated after transection of the
      cervical spinal cord or blockade of alpha-adrenergic receptors by phentolamine,
      and is dose-dependently inhibited by a selective antagonist of the CB1
      cannabinoid receptor. The pressor component is not affected by any of these
      interventions. This suggests that the depressor response is due to inhibition of
      sympathetic tone mediated by CB1 receptors, whereas the pressor component is due
      to a peripheral action that does not involve the same receptors or the
      sympathetic nervous system.

PMID- 7589174
TI  - Corticotropin-releasing factor inhibits antigen-induced plasma extravasation in
      airways.
AB  - We investigated the potential of corticotropin-releasing factor (CRF) to reduce
      neurogenic plasma extravasation in sensitised guinea pig airways evoked by
      antigen challenge. Inhalation of 5% ovalbumin for 2 min in the presence of
      phosphoramidon (2.5 mg/kg, i.v.) increased extravasation of Evans blue dye in the
      trachea and main bronchi. The increase in plasma extravasation induced by antigen
      challenge was significantly reduced by pretreatment with CRF (30 nmol/kg, i.v.)
      (73% in the trachea and 42% in the main bronchi). The inhibition of plasma
      extravasation by CRF (30 nmol/kg, i.v.) alone was not different from the
      inhibition induced by the combination of CRF and the tachykinin NK1 receptor
      antagonist, CP-99,994 (4 mg/kg, i.v.) (73% in the trachea and 38% in the main
      bronchi). CRF (30 nmol/kg, i.v.) inhibited by 32% in the trachea and by 43% in
      the main bronchi plasma extravasation induced by aerosolised bradykinin but did
      not reduce the plasma extravasation caused by aerosolised substance P in the
      presence of phosphoramidon. These findings suggest that CRF reduces ovalbumin
      induced plasma extravasation in guinea pig airways by inhibiting the release of
      tachykinins from primary sensory nerves.

PMID- 7589173
TI  - Effect of pregnancy on vasopressin-mediated responses in guinea-pig uterine
      arteries with intact and denuded endothelium.
AB  - The effect of pregnancy on vasopressin-induced contraction of guinea-pig uterine
      arterial rings was investigated. Initially, vasopressin induced contraction (pD2
      = 9.14) in pregnant guinea-pig uterine artery with greater potency than in non
      pregnant guinea-pig uterine artery (pD2 = 8.77). Removal of the endothelium did
      not affect vasopressin-induced contractions, regardless of pregnancy status. In
      all types of preparations, [d(CH2)5Tyr(Me)2]vasopressin (10-100 nM) and
      [d(CH2)5,D-Ile2,Ile4]vasopressin (300 nM-3 microM) produced parallel rightward
      shifts of the curves for vasopressin. The Schild plots constrained to a slope of
      unity gave the following -log KB values: [d(CH2)5Tyr(Me)2]vasopressin vs.
      [d(CH2)5,D-Ile2,Ile4]vasopressin 8.74 vs. 6.82 and 8.50 vs. 6.72 for non-pregnant
      guinea-pig uterine artery with intact and denuded endothelium, respectively; 8.38
      vs. 6.49 and 8.36 vs. 6.75 for pregnant guinea-pig uterine artery with intact and
      denuded endothelium, respectively. The pKA values for vasopressin itself also did
      not differs between preparations: 6.49 and 6.55 for non-pregnant guinea-pig
      uterine artery with intact and denuded endothelium, respectively; 6.48 and 6.52
      for pregnant guinea-pig uterine artery with intact and denuded endothelium,
      respectively. The receptor reserve (KA/EC50) was significantly greater in
      preparations taken from pregnant than from non-pregnant animals. It is concluded
      that vasopressin-induced contractions of guinea-pig uterine artery are not
      modulated by the endothelium, regardless of pregnancy status. The receptor
      reserve for vasopressin in guinea-pig uterine artery is increased during
      pregnancy, that is not related to the changes of vasopressin receptor affinity
      for vasopressin. It is probable that vasopressin receptors involved in
      vasopressin-induced contraction of all types of vessels studied belong to the V1A
      like subtype.

PMID- 7589172
TI  - Blockade of phencyclidine-induced hyperlocomotion by clozapine and MDL 100,907 in
      rats reflects antagonism of 5-HT2A receptors.
AB  - Whereas haloperidol more potently blocked the locomotion elicited by amphetamine
      (2.5 mg/kg i.p.) than that elicited by phencyclidine (PCP) (20.0 mg/kg s.c.),
      with inhibitory dose50s of 0.04 and 0.09 mg/kg s.c., respectively, clozapine more
      potently blocked the effect of PCP (0.04) than of amphetamine (8.8). Similarly,
      risperidone more potently blocked PCP (0.002) than amphetamine (0.2). In analogy
      to haloperidol, the selective dopamine D2 receptor antagonist, raclopride,
      antagonised amphetamine (0.16) more potently than PCP (0.8) whereas the selective
      5-HT2A receptor antagonist, [R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4
      fluorophenylethyl)]-4- piperidine-methanol] (MDL 100,907), only antagonised PCP
      (0.001) as compared to amphetamine (> 10.0). The potency for inhibition of PCP
      correlated more highly to affinity at 5-HT2A (r = 0.97, P < 0.01) than dopamine
      D2 (0.57, P > 0.05) sites, while the potency for blockade of amphetamine
      correlated more highly with affinity at dopamine D2 (0.94, P < 0.01) than at 5
      HT2A sites (0.37, P > 0.05). In conclusion, in contrast to amphetamine, induction
      of locomotion by PCP is dependent upon functional 5-HT2A receptors, antagonism of
      which by 'atypical' antipsychotics underlies their ability to inhibit PCP-induced
      locomotion.

PMID- 7589176
TI  - The purinoceptors of the guinea-pig isolated taenia caeci.
AB  - The guinea-pig taenia caeci contains both P1 and P2 purinoceptors mediating
      relaxation. The P2 purinoceptors have been further characterized using an
      experimental approach designed to minimise complicating factors. In the presence
      of the adenosine uptake inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI, 300 nM)
      and a pA100 concentration of the P1 purinoceptor antagonist 8
      sulphophenyltheophylline (140 microM), the potency order of agonists was: 2
      methylthio-ATP >> adenosine 5'-triphosphate (ATP) = alpha, beta-methylene ATP >
      beta, gamma-methylene ATP >> uridine 5'-triphosphate. Suramin antagonized ATP
      (pA2 = 5.52 +/- 0.17, Schild plot slope = 0.67 +/- 0.08) and 2-methylthio-ATP
      (pA2 = 5.78 +/- 0.30, Schild plot slope = 1.37 +/- 0.39) while responses to 5'-N
      ethylcarboxamidoadenosine (NECA) were unaffected. The findings suggest that
      suramin, while it is selective for P2 relative to P1 purinoceptors, is not a true
      competitive antagonist. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid
      (PPADS) antagonized ATP in isolated guinea-pig vas deferens, but had no effect on
      responses to ATP in guinea-pig taenia caeci indicating it is selective for P2X
      relative to P2Y purinoceptors.

PMID- 7589175
TI  - Effect of nicardipine on abnormal excitability of CA3 pyramidal cells in
      hippocampal slices of spontaneously epileptic rats.
AB  - The effects of nicardipine, a Ca2+ channel antagonist, on the abnormal
      excitability of hippocampal CA3 neurons in spontaneously epileptic rats (SER), a
      double mutant (zi/zi, tm/tm), were examined to elucidate whether or not the
      abnormality was due to that of Ca2+ channels. An intracellular recording study
      was performed using brain slice preparations of SER 12-15 weeks of age, when SER
      showed both tonic convulsions and absence-like seizures. Bath application of
      nicardipine (10 nM) completely inhibited the depolarizing shifts lasting for 60
      120 ms and accompanying repetitive firings on mossy fiber stimulation in SER.
      However, this drug did not affect the single action potential induced by the
      mossy fiber stimulation in CA3 neurons of SER and normal Wistar rats. In the CA3
      pyramidal neurons of SER, the Ca2+ spikes induced by the depolarizing pulse
      applied in the cell in the presence of tetrodotoxin and tetraethylammonium had a
      different configuration from that in normal Wistar rats. Nicardipine also
      inhibited the Ca2+ spikes in SER CA3 neurons at a concentration (1 nM) that had
      no effect on those in normal Wistar rats, while the Ca2+ spikes in Wistar rat CA3
      neurons were inhibited by 10 nM nicardipine. These findings suggest that the
      abnormal excitability of CA3 pyramidal neurons in SER might be attributed to
      abnormalities of the Ca2+ channels, and that the Ca2+ channel antagonist may be
      effective as an antiepileptic drug.

PMID- 7589177
TI  - Effect of SR 33805 on arterial smooth muscle cell proliferation and neointima
      formation following vascular injury.
AB  - The possible activity of SR 33805 ([[N-[dimethoxy-3,4-phenethyl]-N- methylamino
      propoxyl]-4-benzenesulfonyl]-2-isopropyl-3-methyl-1-in dole), a novel Ca2+
      channel blocker, in early atherogenesis was investigated. In vitro, SR 33805
      strongly inhibited fetal calf serum-induced proliferation of cultured human
      aortic smooth muscle cells with an IC50 value of 0.3 +/- 0.1 microM (n = 3). In
      this respect, SR 33805 was several fold more active than the reference compounds:
      diltiazem, verapamil, nifedipine and fantofarone. SR 33805 was also a potent
      inhibitor of platelet-derived growth factor- or basic fibroblast growth factor
      induced proliferation of human smooth muscle cells. SR 33805 inhibited serum
      stimulated 45Ca2+ uptake in these cells, with an IC50 value of 47 +/- 18 nM. The
      effect of SR 33805 on intimal smooth muscle hyperplasia in rabbit carotid
      arteries subjected to air-drying endothelial injury was then investigated. After
      a 16-day treatment, SR 33805 (6.0 mg/kg/day p.o.) inhibited the development of
      intimal thickening. Under the same experimental conditions, nifedipine,
      verapamil, diltiazem (2 x 6 mg/kg/day p.o.--16 days) and fantofarone (12
      mg/kg/day p.o.--16 days) were inactive. These results show that SR 33805, a novel
      and potent Ca2+ channel blocker, can reduce myointimal thickening following
      endothelial injury.

PMID- 7589178
TI  - Denopamine as an alpha 1H-adrenoceptor antagonist in isolated blood vessels.
AB  - The effects of denopamine, clinically used as a cardiotonic beta 1-adrenoceptor
      agonist, were investigated on alpha-adrenoceptor-mediated contraction in vascular
      preparations of rats, guinea-pigs and rabbits. Norepinephrine, phenylephrine
      (alpha 1-adrenoceptor agonist) and clonidine [and 5-bromo-6-(2-imidazolin-2
      ylamino)quinoxaline (UK 14,304, alpha 2-adrenoceptor agonists)] concentration
      dependently contracted the vascular preparations. Phenylephrine was more potent
      than the alpha 2-adrenoceptor agonists in the rat aorta and carotid artery. The
      reverse was true in the rabbit ear vein. pA2 values for prazosin (rat tissues,
      9.7-10; guinea-pig aorta, 9.1-9.3) and for yohimbine (rat tissues, 6.6-6.9;
      guinea-pig aorta, 6.2-6.3; rabbit ear vein, 7.9) suggested that alpha 1H (high
      affinity for prazosin)-, alpha 1L (lower affinity for prazosin)-, and alpha 2
      adrenoceptors were predominantly distributed in the rat tissues, the guinea-pig
      aorta, and in the rabbit ear vein, respectively. Vasoconstrictions mediated by
      alpha 1H-adrenoceptor subtypes were more susceptible to inhibition by denopamine
      than those mediated by alpha 1L and alpha 2 subtypes. These results suggested
      that in addition to activity as a beta 1-adrenoceptor agonist, denopamine also
      possessed activity as an alpha 1H-adrenoceptor-selective antagonist. These
      actions may contribute to the denopamine-induced decrease in total peripheral
      resistance in vivo.

PMID- 7589179
TI  - Effects of benzoic acid and its analogues on insulin and glucagon secretion in
      sheep.
AB  - The effects of benzoic acid and its analogues on insulin and glucagon secretion
      were investigated in conscious sheep. Intravenous injections of benzoic acid
      increased plasma insulin and glucagon concentrations in a dose-dependent manner
      between 39-1250 mumol/kg, with ED50s for increasing both hormones of about 625
      mumol/kg. Various derivatives of benzoic acid (625 mumol/kg) were administered
      and structure-activity relationships were examined. A single carboxylic group was
      essential for stimulating insulin and glucagon secretion, since both hormone
      responses were abolished with compounds in which the carboxylic group was
      replaced by sulfonic or phosphoric groups, or in which another carboxylic element
      was introduced (phthalic acids). Most of the compounds which introduced other
      elements (amino and hydroxy groups, and halogens) onto the benzene ring had an
      altered stimulating activity. Thus the pancreatic endocrine system can recognize
      the chemical structure of benzoic acid and its derivatives in detail and induce
      insulin and glucagon secretion in sheep.

PMID- 7589180
TI  - The binding interactions of Ro 40-5967 at the L-type Ca2+ channel in cardiac
      tissue.
AB  - Ro 40-5967 [(1S,2S)-2-[2[3-(2-benzamidopropyl]- methylamino]ethyl]-6-fluoro
      1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl- methoxyacetate] is a new Ca2+ channel
      antagonist active at L-type channels. Radioligand binding studies in cardiac
      tissue show that Ro 40-5967 does not inhibit 1,4-dihydropyridine binding, but
      does inhibit diltiazem, desmethoxyverapamil and SR 33557 binding with IC50 values
      of 8 x 10(-9), 10(-8) and 5 x 10(-8) M, respectively. Equilibrium and kinetic
      binding studies showed that Ro 40-5967 inhibited both desmethoxyverapamil and SR
      33557 binding in an apparently competitive manner. Ro 40-5967 defines an
      additional and possibly unique antagonist binding site on the L-type voltage
      gated Ca2+ channel.

PMID- 7589183
TI  - Autoradiographic mapping of [3H]sumatriptan binding in cat brain stem and spinal
      cord.
AB  - In vitro autoradiography was performed on sections of cat brain stem and spinal
      cord using [3H]sumatriptan. Localization studies using 20-25 nM [3H]sumatriptan
      showed specific binding to cells in the trigeminal nucleus caudalis and nucleus
      tractus solitarius of the brain stem and the dorsal horn of the spinal cord. This
      binding was unaffected by 8-hydroxy-dipropylaminotetralin (20 nM), but was
      abolished by 5-carboxamidotryptamine (200 nM). Ketanserin displaced total
      specific binding in the brain stem with a pIC50 of 6.2 but no apparent regional
      specificity. These results indicate that [3H]sumatriptan labels predominantly 5
      HT1D alpha and/or 5-HT1D beta (but not 5-HT1A or 5-HT1F) receptor subtypes in cat
      brain stem and spinal cord.

PMID- 7589184
TI  - Prostanoid-induced contractions are blocked by sulfonylureas.
AB  - The sulfonylureas glibenclamide and tolbutamide are blockers of ATP-regulated K+
      channels. The present study shows that these drugs also block contractions
      induced by prostaglandin F2 alpha, prostaglandin E2 and the thromboxane A2
      mimetic U-46619 on rat aorta. This effect of sulfonylureas is not related to the
      endothelium since it is also found in endothelium-denuded preparations. The
      blockade is specific for prostanoids since contractions with norepinephrine,
      phenylephrine, serotonin, endothelin-1 or K+ (120 mM) are not or much less
      affected. On the other hand, contraction induced by activation of G-proteins with
      aluminium tetrafluoride anion (AlF4-) is significantly blocked by the
      sulfonylureas. Also on rat carotid artery the contraction of prostaglandin F2
      alpha is importantly blocked by glibenclamide. It is concluded that the
      sulfonylureas glibenclamide and tolbutamide exert a specific inhibitory influence
      on prostanoid-induced contractions. This inhibition might be due to interference
      at the level of regulatory G-proteins, since the contractions induced by agonists
      that, like the prostanoids, activate phospholipase C (serotonin, phenylephrine,
      norepinephrine, endothelin) are not blocked.

PMID- 7589185
TI  - The anxiolytic effects of flesinoxan, a 5-HT1A receptor agonist, are not related
      to its neuroendocrine effects.
AB  - The effects of flesinoxan, a selective 5-HT1A receptor agonist, were studied
      under basal non-stress conditions and in the shock-probe burying paradigm.
      Flesinoxan (1 and 3 mg/kg s.c.) significantly reduced burying and freezing
      behaviour, indicating clear anxiolytic properties. Under non-stress conditions,
      injection of 3 mg/kg flesinoxan significantly enhanced plasma corticosterone and
      glucose levels, whereas prolactin secretion was significantly enhanced after both
      1 mg/kg and 3 mg/kg flesinoxan. Flesinoxan (1 and 3 mg/kg) did not suppress shock
      probe stress-induced rises in plasma corticosterone and glucose levels. The
      enhanced plasma prolactin levels induced by flesinoxan were not further affected
      by shock-probe exposure. Our data show that the anxiolytic effects of flesinoxan
      in the shock-probe burying paradigm are not related to increases in plasma
      corticosterone and glucose levels.

PMID- 7589182
TI  - Binding of 1,4-benzodiazepines to a novel [3H]Ro15-4513 binding site in the rat
      spinal cord.
AB  - An alpidem-insensitive benzodiazepine binding site in the rat spinal cord has
      recently been identified in our laboratory. We report here the binding of 23 1,4
      benzodiazepines to this site using [3H]Ro15-4513 (ethyl-8-azido-6-dihydro-5
      methyl-4H-imidazo[1,2- a][1,4]benzodiazepine-3-carboxylate) in the presence of 65
      microM alpidem (6-chloro-2-(4-chlorophenyl)-N,N- dipropylimidazo[1,2-a]pyridine-3
      acetamide). This binding site displays a wide affinity for 1,4-benzodiazepines,
      most of which show much higher affinity for benzodiazepine receptors in various
      brain regions and transfected cell systems. The highest affinity ligands are:
      brotizolam (1-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-
      f][1,2,4]triazolo[4,3-a][1,4]diazepine) (4.3 nM), Ro15-4513 (5.0 nM), Ro42-8773
      (7-chloro-3-[3-(cyclopropylmethoxy)-1-propynyl]-4,5-dihydro- 5-methyl-6H
      imidazo[1,5-a][1,4]benzodiazepine-6-one) (5.7 nM), Ro16-6028 (t-butyl (s)-8-bromo
      11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a][1,4]benzodiazepine-1
      carboxylate) (5.9 nM) and triazolam (8-chloro-6-(2-chlorophenyl)-1-methyl-4H-
      [1,2,4]triazolo[4,3-a][1,4]benzodiazepine) (7.9 nM). The structural feature
      common to these compounds is an imidazo- or triazolo-ring on the 1- and 2
      position of the benzodiazepine. However, the presence of this feature does not
      guarantee high affinity binding as Ro15-1788 (8-fluoro-5,6-dihydro-5-methyl-6-oxo
      4H-imidazo[1,5- a][1,4]benzodiazepine-3-carboxylic acid ethyl ester) (100 nM) and
      Ro23-0364 (6-[2-chlorophenyl]-4H- imidazo[1,5-a][1,4]benzodiazepine-3
      carboxamide) (360 nM) display much lower affinity for this site. Studies are
      currently underway to investigate the functional significance of this unusual
      benzodiazepine binding site.

PMID- 7589181
TI  - Antiparkinsonian action of dextromethorphan in the reserpine-treated mouse.
AB  - Dextromethorphan has been reported to be a weak antagonist of the ion channel
      associated with the NMDA receptor, and to have putative antiparkinsonian activity
      in man. This study looked at the effects of dextromethorphan in normal and
      monoamine-depleted mice, to determine whether it exhibited a behavioural profile
      with regard to motor activity that was consistent with NMDA receptor blockade. In
      normal mice, 5-80 mg/kg i.p. dextromethorphan caused modest muscle relaxation at
      the highest dose in all animals; hyperlocomotion and stereotypy were evident at
      40 mg/kg i.p. in a fraction of mice (4/14). In 24 h reserpine-treated mice,
      locomotion was reinstated by the dopamine D1 receptor agonist 2,3,4,5-tetrahydro
      7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.),
      the dopamine D2 receptor agonist N-n-propyl-N-phenylethyl-p-(3
      hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and L-3,4
      dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in conjunction with benserazide
      100 mg/kg i.p.). Dextromethorphan alone (10-40 mg/kg i.p.) caused non-significant
      arousal of monoamine-depleted mice, but potentiated synergistically movements
      elicited by SKF 38393 and L-DOPA, though not RU 24213. The possible use of
      dextromethorphan as an adjunct to L-DOPA in the treatment of Parkinson's disease
      in man, is discussed.

PMID- 7589189
TI  - NS 1619 activates BKCa channel activity in rat cortical neurones.
AB  - Single channel recordings of large conductance Ca2(+)-activated K+ (BKCa)
      channels were made from neurones isolated from rat motor cortex. Application of
      levcromakalim, pinacidil or diazoxide had no effect on BKCa channel activity in
      excised patches. In contrast, NS 1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5
      trifluoromethyl- 2(3H)benzimidazalone) induced concentration-dependent activation
      of BKCa channels with a calculated EC50 of 32 microM. The NS 1619-induced
      activity was dependent on the presence of free Ca2+ at the intracellular surface,
      but was not associated with a change in channel voltage sensitivity. Niflumic
      acid had no effect on BKCa activity per se but prevented NS 1619-mediated
      activation.

PMID- 7589187
TI  - LSL 60101, a selective ligand for imidazoline I2 receptors, on glial fibrillary
      acidic protein concentration.
AB  - The concentration of the astrocytic marker, glial fibrillary acidic protein
      (GFAP) was quantitated by immunoblotting (Western blotting) in the rat brain
      after treatment with the novel ligand for imidazoline I2 receptors LSL 60101 [2
      (2-benzofuranyl)imidazole] and its 6-methoxy derivative LSL 60125. Chronic (7-21
      days), but not acute (1 day) or short-term (3 days), treatment with LSL 60101 (10
      mg/kg i.p.) markedly increased (44-49%) GFAP immunoreactivity in the rat cerebral
      cortex. In contrast, chronic (7 days) treatment with LSL 60125 (10 mg/kg i.p.)
      did not significantly modify GFAP concentrations. In vitro, both drugs displayed
      moderate high affinity and high selectivity for imidazoline I2 receptors versus
      alpha 2-adrenoceptors; however, only chronic treatment with LSL 60101 (10 mg/kg
      i.p.) but not with LSL 60125 (10 mg/kg i.p.) was associated with an up-regulation
      of imidazoline I2 receptors. These data indicate that glial imidazoline I2
      receptors may have a direct physiological function related to GFAP expression and
      that LSL 60101 could be a good tool for the study of the implication of these
      receptors on astrocyte activation and neuronal regeneration.

PMID- 7589186
TI  - Renal pharmacology of GR138950, a novel non-peptide angiotensin AT1 receptor
      antagonist.
AB  - This paper describes the renal pharmacology of the novel, specific, non-peptide
      angiotensin AT1 receptor antagonist, GR138950 (1-[[3-bromo-2-[2
      [[(trifluoromethyl) sulphonyl] amino] phenyl]-5-benzofuranyl] methyl]-4
      cyclopropyl-2-ethyl-1H-imidazole-5- carboxamide). When administered to
      anaesthetised salt-replete dogs, GR138950 caused renal vasodilatation and
      significant increases in sodium and urine excretion. No change in glomerular
      filtration rate was observed indicating that the natriuresis was a consequence of
      inhibition of tubular sodium reabsorption. Qualitatively similar but less marked
      changes in renal function were observed in response to the angiotensin converting
      enzyme inhibitor, captopril, although in contrast to GR138950, captopril also
      caused a small but significant fall in mean blood pressure. Intra-renal artery
      infusion of exogenous angiotensin II resulted in dose-related renal
      vasoconstriction and decreases in urine excretion, sodium excretion, fractional
      excretion of sodium and glomerular filtration rate. These renal effects of
      angiotensin II were all markedly antagonised by GR138950. We conclude that
      GR138950 is an effective antagonist of the renal haemodynamic and excretory
      actions of endogenous and exogenous angiotensin II.

PMID- 7589188
TI  - Tyrosine-iodination converts the delta-opioid peptide antagonist TIPP to an
      agonist.
AB  - The binding properties and pharmacological activities of H-Tyr(3'-I)-Tic-Phe-Phe
      OH ([Tyr(3'-I)1]TIPP) were studied. Similar to the delta-opioid receptor
      antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP), [Tyr(3'-I)1]TIPP is a selective and
      potent ligand at delta-opioid receptors. The displacement curve of
      [3H]diprenorphine binding by [Tyr(3'-I)1]TIPP was shifted to the right in the
      presence of Na+ and 5'-guanylylimidodiphosphate, suggesting that it acted as a
      delta-opioid receptor agonist. [Tyr(3'-I)1]TIPP also behaved as a full agonist in
      the mouse vas deferens assay and its effect was both naloxone- and TIPP
      reversible. These data show that monoiodination at the 3'-position of the N
      terminal tyrosine aromatic ring of TIPP converted it from a potent and selective
      antagonist to a full agonist at delta-opioid receptors.

PMID- 7589192
TI  - 4-Aminopyridine-induced phasic contractions in rat caudal epididymis are mediated
      through release of noradrenaline.
AB  - 4-Aminopyridine, a K+ channel blocker, evoked phasic contractions in the caudal
      duct of the rat epididymis. The 4-aminopyridine-induced contractile response was
      either inhibited or prevented by the alpha 1-adrenoceptor antagonists, prazosin
      (IC50 = 2.7 nM) and benoxathian (IC50 = 14.6 nM). Blockers (1 microM) of alpha 2
      adrenoceptors and purinoceptors but not of beta-adrenoceptors or muscarinic
      receptors caused a small but statistically significant reduction of the 4
      aminopyridine-induced response. 4-Aminopyridine lost its ability to induce
      contractions after noradrenergic nerves had been destroyed by 6-hydroxydopamine.
      In addition, protriptyline and xylamine, blockers of noradrenaline uptake, also
      inhibited the 4-aminopyridine-induced contractile response. However, other
      putative K+ channel blockers (tetraethylammonium ion, quinine, quinidine and
      glibenclamide) did not cause the muscle to contract. These findings demonstrate
      that the 4-aminopyridine-induced release of noradrenaline and adenosine 5'
      triphosphate as co-transmitters results from membrane depolarization due to 4
      aminopyridine blockade of K+ channels in noradrenergic nerve terminals. The 4
      aminopyridine-sensitive K+ channels might thus play a physiological role in
      regulating the nerve membrane potential and neurotransmission in the rat caudal
      epididymis.

PMID- 7589194
TI  - Effects of the competitive NMDA receptor antagonist CGP 37849 on performance of
      reference and working memory tasks by rats.
AB  - The effects of the competitive NMDA receptor antagonist CGP 37849 (DL-(E)-2-amino
      4-methyl-5-phosphono-3-pentenoic acid) were tested in rats performing (1) a
      nonspatial working memory task, and (2) a reference memory task that was either
      partly or fully learnt. CGP 37849 attenuated accuracy in all three tests,
      suggesting that sensorimotor effects may obscure any drug effects on memory
      itself.

PMID- 7589193
TI  - Antidepressant-like effect by postsynaptic 5-HT1A receptor activation in mice.
AB  - The antidepressant-like effect of 5-(3(-)[((2S)-1,4-benzodioxan-2
      ylmethyl)amino]propoxy)-1,3- benzodioxole (MKC-242), a novel 5-HT1A receptor
      agonist, was studied in the forced swimming test in mice injected i.c.v. with 5,7
      dihydroxytryptamine to destroy 5-HT neurons or treated with p-chlorophenylalanine
      to inhibit 5-HT synthesis. MKC-242 reduced immobility time of mice pretreated
      with vehicle and these drugs, although it did not affect their locomotor
      activity. The anti-immobility effect was antagonized by 5-HT1A receptor
      antagonists such as propranolol and N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin
      1-yl)-2-phenylpropana mide. These findings support the hypothesis that
      postsynaptic 5-HT1A receptors play an important role in the antidepressant-like
      effect of 5-HT1A receptor agonists.

PMID- 7589195
TI  - Transdermal nitroglycerin prevents nonsteroidal anti-inflammatory drug
      gastropathy.

PMID- 7589190
TI  - Diazepam induces tolerance in the isolated skin of Pleurodema thaul.
AB  - The effects of the long-term administration of diazepam on the potential
      difference and short-circuit current of the isolated skin of the toad Pleurodema
      thaul (P. thaul) were investigated. Diazepam applied in a concentration range of
      4.6 x 10(-6) to 5.2 x 10(-5) M decreased both electrical parameters. This
      response was unaffected by flumazenil indicating that the action of diazepam is
      not induced through benzodiazepine receptors. Induction of tolerance to diazepam
      on its observed effects on potential difference and short-circuit current was
      obtained by the administration of a single dose of the drug in a slow release
      preparation. Skins tolerant to diazepam were also tolerant to the acute effects
      of verapamil on both electric parameters. Tolerance to diazepam effects was
      partly reversed by increasing Ca2+ concentration in the inner bathing solution.
      The results are consistent with a Ca2+ channel blocking effect of diazepam in the
      P. thaul skin.

PMID- 7589196
TI  - Absence of detectable striatal dopamine D4 receptors in drug-treated
      schizophrenia.
AB  - The difference between saturable binding of [3H]emonapride (to D2, D3 and D4
      receptors) and [125I]epidepride (to D2 and D3 receptors) was used to determine
      dopamine D4 receptors in putamen taken post-mortem from antipsychotic-treated
      schizophrenic subjects and matched controls. Despite an overall increase in D2/D3
      receptor density in schizophrenia, reflecting prior antipsychotic drug treatment,
      striatal D4 receptors were not significantly detectable in either controls or
      schizophrenic subjects.

PMID- 7589197
TI  - Assessment of cocaine-like discriminative stimulus effects of dopamine D3
      receptor ligands.
AB  - The highly selective dopamine D3 receptor ligand, (+)-PD 128907 4aR10bR-(+)-trans
      3,4,4a,10b-tetrahydro-4-n-propyl-2H5H[4,3- b]-1,4- oxazin-9-ol), and other
      dopamine D3 receptor ligands, (+/-)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin
      and (+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin, substituted for the
      discriminative stimulus effects of cocaine in rats, an animal model of subjective
      effects in humans. Substitution only occurred at doses that markedly decreased
      responding. These results suggest that dopamine D3 receptors may be involved in
      the subjective effects of cocaine, and therefore may be a target for the
      discovery of treatments for cocaine dependence.

PMID- 7589200
TI  - Presynaptic depression of inhibitory postsynaptic potentials by metabotropic
      glutamate receptors in rat hippocampal CA1 pyramidal cells.
AB  - The effects of the metabotropic glutamate (mGlu) receptor agonists (+/-)-trans-1
      aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or 1S,3R-ACPD on gamma
      aminobutyric acid (GABA)-mediated inhibitory synaptic responses have been
      investigated in vitro in CA1 pyramidal cells of rat hippocampal slices. Bath
      application of both agonists depolarized the resting membrane potential and
      increased membrane resistance. Simultaneously, the afterhyperpolarization induced
      by a burst of spikes as well as spike accomodation were blocked. Stimulation of
      the stratum radiatum induced in CA1 pyramidal cells an early excitatory
      postsynaptic potential (EPSP) followed by a fast GABAA and a slow GABAB-mediated
      inhibitory postsynaptic potentials (IPSPs). All synaptic responses were dose
      dependently depressed by mGlu receptor agonists. At low concentration, (+/-)
      trans-ACPD (10-100 microM) and 1S,3R-ACPD (10 microM) consistently reduced the
      EPSP, slightly depressed the fast IPSP but greatly decreased the slow IPSP.
      Increasing the concentration of mGlu receptor agonists to 200 microM and 50
      microM, respectively further depressed the EPSP and dramatically reduced the
      amplitude of both IPSPs. In the presence of the glutamate receptor antagonists 6
      cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D-(-)-2-amino-5
      phosphonovaleric acid (30 microM), monosynaptically evoked IPSPs were still
      depressed by mGlu receptor agonists. In the same conditions, the discharge
      frequency of spontaneous IPSPs which reflect the activity of GABAergic
      interneurons was enhanced by low doses of mGlu receptor agonists but depressed
      with higher concentrations. On the other hand, the postsynaptic hyperpolarization
      and decrease in membrane resistance induced by the GABAB receptor agonist
      baclofen applied in the bath or by microiontophoresis were not affected by mGlu
      receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589199
TI  - Increased 5-HT2 receptor-mediated behavior 11 days after shock in learned
      helplessness rats.
AB  - In the learned helplessness procedure, rats can be differentiated into two
      distinct groups. Learned helplessness (LH) rats do not learn to escape a
      controllable shock while non-learned helplessness (NLH) rats learn this response.
      This deficit in performance in LH rats lasted for 11 days. In LH rats,
      pretreatment with acute desipramine (15 mg/kg i.p.) or chronic diazepam (0.95
      mg/kg/day p.o. for 7 days) did not produce recovery from this deficit of
      performance, but pretreatment with chronic desipramine (17.7 mg/kg/day p.o. for 7
      days) or chronic mianserin (6.1 mg/kg/day p.o. for 7 days) led to recovery.
      Before presentation of uncontrollable shock, there was no difference between LH
      and NLH rats, but 11 days after the shock, head shakes induced by (+/-)-1-(2,5
      demethoxy-4-iodophenyl)-2-aminopropane (DOI) in LH rats was significantly more
      frequent than those in NLH and naive rats without change of [3H]ketanserin
      binding. The basal corticosterone level was higher in LH rats than in NLH rats.
      These findings suggest that the learned helplessness model is a reliable animal
      model of depression accompanied by 5-HT2 receptor hypersensitivity.

PMID- 7589201
TI  - Binding of d-threo-[11C]methylphenidate to the dopamine transporter in vivo:
      insensitivity to synaptic dopamine.
AB  - The regional distribution of [11C]d-threo-methylphenidate in mouse brain was very
      similar to that of [3H]WIN 35,428 ((-)-2 beta-carbomethoxy-3 beta-(4
      fluorophenyl)tropane), and the two radioligands were displaced from striatum
      similarly after administration of the potent cocaine analog RTI-55 ((-)-2 beta
      carbomethoxy-3 beta-(4-iodophenyl)tropane). However, while striatal [3H]WIN
      35,428 increased between 5 and 30 min, striatal [11C]d-threo-methylphenidate
      halved. Thus [11C]d-threo-methylphenidate binds similarly to but more reversibly
      than [3H]WIN 35,428. The methyl ester of L-DOPA (L-3,4-dihydroxyphenylalanine;
      200 mg/kg) plus benserazide plus clorgyline, which markedly elevates rat striatal
      extracellular dopamine (Wachtel and Abercrombie, 1994, J. Neurochem. 63, 108),
      decreased the mouse striatum-to-cerebellum ratio for [11C]d-threo-methylphenidate
      at 30 min by 13% (P < 0.05). In positron emission tomographic (PET) baboon
      studies [11C]d-threo-methylphenidate binding was insensitive to drugs expected to
      lower endogenous dopamine. These experiments suggest that normal synaptic
      dopamine does not compete for binding with [11C]d-threo-methylphenidate, and will
      not affect PET measures of dopamine transporter availability.

PMID- 7589202
TI  - Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels,
      KV1.2 and KV1.4.
AB  - We investigated the effects of the antiarrhythmic drugs, quinidine, disopyramide,
      flecainide, clofilium, verapamil, and the bradycardic drug, bertosamil, on the
      currents of the cloned K+ channels, KV1.2 (IK(V1.2)) and KV1.4 (IK(V1.4)), using
      the Xenopus oocyte expression system. Both IK(V1.2) and IK(V1.4) were inhibited
      in a concentration-dependent manner by quinidine (10 microM to 1 mM), flecainide
      (10 microM to 1 mM), clofilium (10-300 microM), verapamil (10 microM to 1 mM) and
      bertosamil (10 microM to 1 mM) but not by disopyramide (10 microM to 1 mM). The
      inhibitory effects of clofilium, verapamil and bertosamil on IK(V1.2) were time
      dependent. The decay time course of IK(V1.4) was accelerated by clofilium,
      verapamil and bertosamil, but decelerated by quinidine and flecainide. These
      results indicate that IK(V1.2) and IK(V1.4) are targets for the four
      antiarrhythmic drugs and the bradycardic drug.

PMID- 7589203
TI  - Effects of irbesartan (SR47436/BMS-186295) on angiotensin II-induced pressor
      responses in the pithed rat: potential mechanisms of action.
AB  - The effects of two new non-peptide angiotensin receptor antagonists, irbesartan
      (SR 47436/BMS-186295, (2-n-butyl-4-spirocyclopentane-1-[((2'-tetrazol-5
      yl)bipheny l-4-yl)methyl]2 - imidazolin-5-one) and SR 47155A (2-n-butyl-4
      spirocyclopentane-1-[((2'-carboxy)biphenyl-4-yl)methy l]2- imidazolin-5-one,
      trifluoroacetate), on angiotensin II-induced pressor responses were studied in
      the pithed rat in comparison to losartan, EXP 3174 and
      [Sar1,Val5,Ala8]angiotensin II. SR 47155A (1-10 mg/kg i.v.) and losartan (1-10
      mg/kg i.v.) shifted dose dependently the dose-response curve of angiotensin II to
      the right without affecting the maximal response. SR 47436 (0.3-10 mg/kg i.v.),
      EXP 3174 (0.03-1 mg/kg i.v.) and [Sar1,Val5,Ala8]angiotensin II (0.03-1 mg/kg
      i.v.) induced, at least at high doses, a non-parallel shift to the right of the
      angiotensin II dose-response curve and this was associated with a reduction of
      the maximal response. During a 70 min period, the effect of
      [Sar1,Val5,Ala8]angiotensin II (1 mg/kg i.v.) on the angiotensin II (0.3
      microgram/kg i.v.)-induced pressor response was shown to be reversible, the
      effect of SR 47155A (10 mg/kg i.v.) was partially reversible and the effect of SR
      47436 (3 mg/kg i.v.), EXP 3174 (1 mg/kg i.v.) or losartan (6 mg/kg i.v.) was not
      reversed at the end of this 70 min period. Administration of SR 47155A (10 mg/kg
      i.v.) before SR 47436 (1-10 mg/kg i.v.) reversed the reduced angiotensin II
      maximal response induced by SR 47436. Administration of SR 47436 (10 mg/kg i.v.)
      before SR 47155A (1-10 mg/kg i.v.) prevented the full development of the pressor
      response as observed in the absence of SR 47436. In the pithed rat, SR 47436 (30
      mg/kg i.v.) and losartan (30 mg/kg i.v.) reduced the change in diastolic blood
      pressure induced by electrical stimulation of the spinal cord only at low
      stimulation rates. Taken together these results indicate that SR 47436, under in
      vivo conditions, is a potent non-peptide angiotensin receptor antagonist. The
      type of antagonism (partially insurmountable but selective) can be explained by
      different theoretical models which are discussed.

PMID- 7589191
TI  - Evidence that dopamine D3 receptors participate in clozapine-induced hypothermia.
AB  - In analogy to the dopamine D3 receptor agonist, (+)-7-OH-DPAT (7-hydroxy-2-(di-n
      propylamino)tetralin) (0.01-0.63 mg/kg s.c.), clozapine dose-dependently (0.63
      40.0 mg/kg s.c.) elicited hypothermia in rats. Haloperidol and raclopride, mixed
      dopamine D2/D3 receptor antagonists, failed, in contrast, to modify core
      temperature. Further, they dose-dependently inhibited the action of clozapine
      with inhibitory dose50 values (ID50) of 0.3 mg/kg s.c., in each case. The
      preferential dopamine D3 versus D2 receptor antagonist, (+)-AJ 76 (cis-(+)-5
      methoxy-1-methyl-2-(n-propylamino)tetralin) (ID50 = 2.8), and the selective
      dopamine D3 versus D2 receptor antagonist, (+/-)-S 11566 ((+/-)(-)[7-(N,N
      dipropylamino)-5,6,7,8-tetrahydro-naphtho(2,3b) dihydro,2,3-furane]) (ID50 = 1.6)
      likewise blocked the action of clozapine without reducing core temperature alone.
      The action of (+/-)-S 11566 was stereospecific in that its active eutomer, (+)-S
      14297 (ID50 = 1.0), also inhibited the action of clozapine whereas its inactive
      distomer, (-)-S 17777 (ID50 > 10.0), was not effective. Antagonist potency for
      blockade of clozapine-induced hypothermia correlated powerfully both with potency
      for blockade of (+)-7-OH-DPAT-induced hypothermia (r = 0.98) and with affinity at
      cloned human dopamine D3 receptors transfected into Chinese hamster ovary (CHO)
      cells (r = 0.92). In conclusion, these data suggest that dopamine D3 receptors
      may be involved in the induction of hypothermia by clozapine in the rat.

PMID- 7589198
TI  - Neuroreceptor quantification in vivo by the steady state principle and
      [123I]iomazenil in rats.
AB  - A steady state method for neuroreceptor quantification in vivo in small
      laboratory animals is described, using [123I]iomazenil as tracer for the
      benzodiazepine receptor. The method was used for determination of the receptor
      equilibrium constant for a non-radioactive ligand, flumazenil, in rats and
      involved measurement of the nonspecific binding of [123I]iomazenil. Thirty-five
      animals were intravenously infused for 2 h with [123I]iomazenil and flumazenil in
      different proportions to obtain occupancies of the benzodiazepine receptor from
      close to 0 to about 99%. The nonspecific binding of iomazenil in brain tissue was
      calculated by an iterative procedure from the data for the highly blocked
      animals, and it was found to be 1.04 ml per ml plasma (n = 6). The mean cortical
      Kd of flumazenil was 21 +/- 11 nM (n = 19). The method is discussed with special
      reference to the problems of ascertaining steady state and nonspecific binding.

PMID- 7589204
TI  - kappa-Opioid receptor agonists improve pirenzepine-induced disturbance of
      spontaneous alternation performance in the mouse.
AB  - We investigated the effects of kappa-opioid receptor agonists such as dynorphin A
      (1-13) and U-50,488H on the muscarinic M1-selective receptor antagonist
      pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation
      performance in the mouse. Although dynorphin A-(1-13)(1-5.6 micrograms, i.c.v.)
      or U-50,488H ((+/-)trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-
      benzeneacetamide, methanesulfonate hydrate) (0.1-1 mg/kg, i.p.) alone did not
      influence either spontaneous alternation performance or total arm entries,
      pirenzepine (3 micrograms, i.c.v.) impaired spontaneous alternation performance
      without producing any significant change in total arm entries. In contrast,
      dynorphin A-(1-13) (3 and 5.6 micrograms, i.c.v.) and U-50,488H (0.3 and 1 mg/kg,
      i.p.) ameliorated the pirenzepine (3 micrograms, i.c.v.)-induced impairment of
      spontaneous alternation performance. The ameliorating effects of dynorphin A-(1
      13)(3 micrograms, i.c.v.) and U-50,488H (0.3 mg/kg, i.p.) were almost completely
      reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa
      opioid receptor antagonist. These results suggest that the stimulation of kappa
      opioid receptors improves memory dysfunctions resulting from the blockade of
      muscarinic M1 receptors.

PMID- 7589205
TI  - 3,4-Diaminopyridine and choline increase in vivo acetylcholine release in rat
      striatum.
AB  - We investigated the effects of choline, 3,4-diaminopyridine and their combination
      on acetylcholine release from the corpus striatum of freely moving rats which
      were treated or not with atropine. Intraperitoneal administration of choline or
      intrastriatal administration of 3,4-diaminopyridine increased acetylcholine
      levels in striatal dialysates in a dose-dependent manner. When 3,4
      diaminopyridine treatment was combined with choline, the observed effect was
      considerably greater than the sum of the increases produced by choline or 3,4
      diaminopyridine alone. Administration of atropine (1 microM) in the dialysing
      medium was also found to be effective to stimulate striatal acetylcholine levels.
      3,4-Diaminopyridine did not affect acetylcholine levels under these conditions.
      Whereas the choline-induced increase in acetylcholine release was significantly
      potentiated by atropine, co-administration of 3,4-diaminopyridine with choline
      failed to produce a further significant increase in the presence of atropine.
      These results suggest that a highly effective means for increasing acetylcholine
      release involves two concurrent treatments that increase neuronal choline levels
      and inhibition of the negative feedback modulation of acetylcholine release.

PMID- 7589206
TI  - Regional haemodynamic effects of platelet activating factor in the rat.
AB  - The effects of platelet activating factor (PAF) on haemodynamics in the absence
      and presence of the potent PAF receptor antagonist TCV-309 (3-bromo-5-[N-phenyl-N
      [2-[[2-(1,2,3,4-tetrahydro-2- isoquinolyl
      carbonyloxy)ethyl]carbamoyl]ethyl]carbamoyl]-1- propylpyridinium nitrate) were
      studied by the microsphere technique in pentobarbitone-anaesthetized rats. I.v.
      infusion of the low dose PAF (0.05 microgram kg-1 min-1) did not significantly
      alter mean arterial pressure, cardiac output or total peripheral resistance but
      increased arterial conductances in the stomach, intestine, caecum and colon and
      reduced conductance in the spleen. I.v. infusion of the high dose of PAF (0.3
      microgram kg-1 min-1) markedly reduced mean arterial pressure (-53 mm Hg) and
      cardiac output (-62%) and insignificantly increased total peripheral resistance.
      Arterial conductances in the lungs, stomach, intestine, caecum and colon, kidneys
      and spleen were reduced and those in the heart and muscle were increased. TCV-309
      (10 micrograms kg-1) abolished all changes in arterial pressure, cardiac output
      and total peripheral resistance and arterial conductances elicited by either the
      low or the high dose of PAF. The results show that a non-hypotensive dose of PAF
      caused vasodilatation of the gastrointestinal organs and vasoconstriction of the
      spleen. A high dose of PAF which markedly decreased arterial pressure and cardiac
      output caused vasodilatation of the heart and muscle and vasoconstriction of the
      lungs (bronchial), gastrointestinal organs, kidneys and spleen. All haemodynamic
      changes were blocked by TCV-309 indicating the involvement of PAF receptors.

PMID- 7589207
TI  - Effects of various dopamine uptake inhibitors on striatal extracellular dopamine
      levels and behaviours in rats.
AB  - In vivo central effects of some dopamine uptake inhibitors were evaluated in both
      brain microdialysis and behavioural studies in rats, and compared with their in
      vitro affinities to dopamine uptake sites. IC50 values of GBR12909 (1-[2- bis(4
      fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine), diclofensine,
      mazindol, amfonelic acid and nomifensine for inhibiting 1 nM [3H]GBR12935 (1-[2
      (diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) binding to rat striatal
      membrane were 7.0, 36, 81, 187 and 290 nM, respectively. In the brain
      microdialysis study, dopamine levels in the striatal dialysates were increased to
      16.3- (GBR12909), 14.1- (nomifensine), 4.8- (diclofensine) and 1.9-fold
      (amfonelic acid) the respective basal levels 40-60 min after i.p. administration
      (0.1 mmol/kg) and thereafter decreased slowly but remained at the elevated levels
      for a further 3 h, while mazindol gradually increased dopamine levels though less
      pronouncedly than others (1.7-fold 200 min after administration). Remarkable and
      comparable stereotyped behaviours (licking and forepaw treading) were
      continuously observed at least for 3 h after administration of GBR12909,
      nomifensine and amfonelic acid, while stereotypies induced by diclofensine and
      mazindol were moderate and marginal, respectively. In vivo potencies of dopamine
      uptake inhibitors to increase the extracellular dopamine levels in the striatum
      tended to correlate with their in vitro affinities to dopamine uptake sites
      except in the case of nomifensine, and correlated significantly with their
      potencies to induce stereotyped behaviours except in the case of amfonelic acid.
      Based on these findings, pharmacological characteristics of these dopamine uptake
      inhibitors are discussed.

PMID- 7589208
TI  - Early administration of YT-146, an adenosine A2 receptor agonist, inhibits
      neointimal thickening after rat femoral artery endothelium injury.
AB  - Adenosine is known to inhibit vascular smooth muscle cell proliferation in vitro
      via adenosine A2 receptor activation. We tested the inhibitory effect of an
      adenosine A2 receptor agonist, 2-octynyladenosine (YT-146), on in vivo intimal
      thickening following a photochemically induced injury of the endothelium of rat
      femoral artery. YT-146 (1 mg/kg/day) was administered s.c. for the first 3, 7 or
      28 days after the injury. YT-146 significantly decreased neointimal area and the
      ratio of intima to medial area measured 28 days after the injury, regardless of
      the duration of administration. These results suggest that YT-146 may inhibit the
      early events of neointimal formation. The effect is long lasting and is not
      reversed even if YT-146 is stopped after a short course of administration.

PMID- 7589209
TI  - Effects of alpha-trinositol administered extra- and intracellularly (using
      liposomes) on rat aorta rings.
AB  - The effects of alpha-trinositol, a D-myo-inositol [1,2,6]trisphosphate
      derivative, were studied on de-endothelised rat aorta rings. The substance was
      applied extracellularly as well as intracellularly (by using liposomes as drug
      carriers). Upon extracellular administration, the drug reduced the level of
      contraction induced by 40 mM K+ or by phenylephrine (10(-5) M). No effects were
      observed on relaxed preparations. Liposomes containing alpha-trinositol induced a
      dose-dependent contraction of the preparations under resting tension with a
      threshold of 10(-5) M in the aqueous phase. These contractions were heparin
      insensitive but were significantly blocked by D-600 (10(-5) M) (an L-type Ca2+
      channel blocker) or in Ca(2+)-free medium. Our data suggest that alpha-trinositol
      has a plasmalemmal mechanism of action which could involve Ca2+ influx from the
      extracellular space.

PMID- 7589210
TI  - Potentiating and inhibitory effects of periodate-oxidized ATP analogs on
      contractions of vas deferens to ATP.
AB  - Previous studies have shown that treatment of guinea-pig isolated vas deferens
      with the affinity label periodate-oxidized ATP (2',3'-dialdehyde ATP), results in
      two irreversible effects on biphasic contractile responses to ATP, i.e.,
      potentiation of the P2X purinoceptor-mediated first phase and inhibition of the
      ecto-kinase-mediated second phase. The present experiments were designed to
      evaluate whether periodate-oxidized ADP, periodate-oxidized AMP, and periodate
      oxidized adenosine, produce similar effects. Periodate-oxidized ATP and periodate
      oxidized ADP (10(-2) M) elicited contraction of the vas deferens (periodate
      oxidized ATP > periodate-oxidized ADP; periodate-oxidized AMP and periodate
      oxidized adenosine had no agonist activity. After incubation of the preparations
      for 5 min with 10(-2) M periodate-oxidized ATP, periodate-oxidized ADP, periodate
      oxidized AMP or periodate-oxidized adenosine, the first phase of contraction to
      submaximal ATP concentrations was potentiated. Simultaneously, periodate-oxidized
      ATP, periodate-oxidized ADP and periodate-oxidized AMP inhibited the second
      contractile phase, whereas periodate-oxidized adenosine did not. The results
      indicate that the requirement for 5'-phosphate to produce potentiation and
      inhibition is different: 5'-phosphate is not needed to potentiate the first phase
      of contraction to ATP, but at least one 5'-phosphate is required to inhibit the
      second phase of contraction.

PMID- 7589211
TI  - Characterisation of delta-subunit containing GABAA receptors from rat brain.
AB  - Polyclonal antibodies have been raised in rabbits against the predicted
      cytoplasmic loop region of the delta-subunit of the GABAA receptor. These
      specifically identify the expressed fragment by Western blot but do not cross
      react with analogous polypeptides from the gamma 1, gamma 2 or gamma 3-subunits.
      Polyclonal antisera immunoprecipitated [3H]muscimol binding sites from several
      brain regions consistent with the reported distribution of delta-subunit mRNA and
      also detected the delta-subunit by Western blot, identifying a polypeptide of
      55KDa. Receptors immunoprecipitated from rat brain with the delta-antisera
      exhibited an atypical profile with respect to their radioligand binding
      properties. Receptors immunoprecipitated from all regions tested bound
      [3H]muscimol, but did not bind benzodiazepine site ligands [3H]Ro 15,1788 or
      [3H]flunitrazepam with high affinity. Receptors containing a delta-subunit
      accounted for 10.7 +/- 2% of all GABAA receptors ([3H]muscimol binding sites) in
      the rat central nervous system as deduced from quantitative immunoprecipitation
      experiments, the largest population being in the cerebellum where approximately
      27% of all receptors contained a delta-subunit. The pharmacology of the GABA
      (gamma-aminobutyric acid) binding site on receptors immunoprecipitated from
      cerebellum with gamma 2 and delta-antisera was compared. The rank order of
      potency of a series of 6 compounds to compete for [3H]muscimol binding sites was
      similar in these two populations, but muscimol had a significantly higher
      affinity for receptors containing the delta-subunit. These receptors therefore
      comprise a novel population of GABAA receptors which do not bind benzodiazepines
      but have a 5-fold higher affinity for muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589212
TI  - PCA-4248, a PAF receptor antagonist, inhibits PAF-induced phosphoinositide
      turnover.
AB  - The effect of a new PAF (platelet activating factor; 1-O-alkyl-2-acetyl-sn
      glycero-3-phosphoryl-choline) receptor antagonist, PCA-4248 (2-phenylthio)ethyl-5
      metoxycarbonyl-2,4,6-trimethyl-1, 4-dihydropyridine-3-carboxylate), on
      phosphoinositide turnover evoked by PAF was investigated. PAF treatment resulted
      in an increased 32P incorporation into phosphoinositides and phosphatidic acid in
      rabbit platelets. Treatment with PCA-4248 abolished both effects in a dose
      dependent manner, 10 microM being the most effective dose. In thrombin stimulated
      platelets, phosphoinositide turnover was not influenced by PCA-4248. In addition,
      PAF caused a rapid and significant increase in protein phosphorylation. Thus, PAF
      treatment resulted in a marked phosphorylation of two proteins of 47 kDa and 20
      kDa. Treatment with PCA-4248 resulted in an inhibition of these actions.
      Serotonin secretion evoked by PAF was also inhibited by PCA-4248. It is concluded
      that PCA-4248 antagonizes the PAF effects by acting as a competitive antagonist
      at the PAF receptor level as evidenced from binding studies.

PMID- 7589213
TI  - 8-substituted adenosine and theophylline-7-riboside analogues as potential
      partial agonists for the adenosine A1 receptor.
AB  - A series of 8-substituted adenosine and theophylline-7-riboside analogues (28 and
      9 compounds, respectively) was tested on adenosine A1 and A2A receptors as an
      extensive exploration of the adenosine C8-region. Alkylamino substituents at the
      8-position cause an affinity decrease for adenosine analogues, but an affinity
      increase for theophylline-7-riboside derivatives. The affinity decrease is
      probably due to a direct steric hindrance between the C8-substituent and the
      binding site as well as to electronic effects, not to a steric influence on the
      ribose moiety to adopt the anti conformation. The 8-substituents increase the
      affinity of theophylline-7-riboside analogues probably by binding to a lipophilic
      binding site. The intrinsic activity was tested in vitro for some 8-substituted
      adenosine analogues, by determining the GTP shift in receptor binding studies and
      the inhibition of adenylate cyclase in a culture of rat thyroid FRTL-5 cells, and
      in vivo in the rat cardiovascular system for 8-butylaminoadenosine. Thus, it was
      shown that 8-ethyl-, 8-butyl-, and 8-pentylamino substituted analogues of
      adenosine may be partial agonists in vitro, and that 8-butylaminoadenosine is a
      partial agonist for the rat cardiovascular A1 receptor in vivo.

PMID- 7589214
TI  - Muscarinic M2 receptor synthesis: study of receptor turnover with
      propylbenzilylcholine mustard.
AB  - We have investigated the rate and the functional responsiveness of the newly
      synthesised M2 muscarinic receptors in HEL 299 cells following
      propylbenzilylcholine mustard treatment at 37 degrees C. Propylbenzilylcholine
      mustard induced a dose-dependent loss of the hydrophilic ligand [3H]N
      methylscopolamine binding sites with 80% inactivation at 0.1 microM. The rate of
      muscarinic receptor synthesis in these cells, estimated from wash-out experiments
      following propylbenzilylcholine mustard treatment, was very slow and returned to
      control values after 36 h of propylbenzilylcholine mustard removal. The recovery
      of muscarinic receptors was blocked by the cycloheximide pre-treatment,
      indicating the synthetic pathway for the new receptors. In control cells as well
      as in cells treated with propylbenzilylcholine mustard and allowed to recover for
      12 h, carbachol still inhibited forskolin-induced cAMP accumulation. These
      results show that (i) the rate of M2 muscarinic receptor synthesis is slow (ii)
      the recovery of receptors is mainly through increased synthesis and (iii) the
      newly synthesised receptors retain their full functional activity.

PMID- 7589215
TI  - Physostigmine, galanthamine and codeine act as 'noncompetitive nicotinic receptor
      agonists' on clonal rat pheochromocytoma cells.
AB  - The acetylcholine esterase inhibitor (-)-physostigmine has been shown to act as
      agonist on nicotinic acetylcholine receptors from muscle and brain, by binding to
      sites on the alpha-polypeptide that are distinct from those for the natural
      transmitter acetylcholine (Schroder et al., 1994). In the present report we show
      that (-)-physostigmine, galanthamine, and the morphine derivative codeine
      activate single-channel currents in outside-out patches excised from clonal rat
      pheochromocytoma (PC12) cells. Although several lines of evidence demonstrate
      that the three alkaloids act on the same channels as acetylcholine, the
      competitive nicotinic antagonist methyllycaconitine only inhibited channel
      activation by acetylcholine but not by (-)-physostigmine, galanthamine or
      codeine. In contrast, the monoclonal antibody FK1, which competitively inhibits (
      )-physostigmine binding to nicotinic acetylcholine receptors, did not affect
      channel activation by acetylcholine but inhibited activation by (-)
      physostigmine, galanthamine and codeine. The three alkaloids therefore act via
      binding sites distinct from those for acetylcholine, in a 'noncompetitive'
      fashion. The potency of (-)-physostigmine and related compounds to act as a
      noncompetitive agonist is unrelated to the level of acetylcholine esterase
      inhibition induced by these drugs. (-)-Physostigmine, galanthamine and codeine do
      not evoke sizable whole-cell currents, which is due to the combined effects of
      low open-channel probability, slow onset and slow inactivation of response. In
      contrast, they sensitize PC12 cell nicotinic receptors in their submaximal
      response to acetylcholine. While the abundance of nicotinic acetylcholine
      receptor isoforms expressed in PC12 cells excludes identification of specific
      nicotinic acetylcholine receptor subtypes that interact with noncompetitive
      agonists, the identical patterns of single-channel current amplitudes observed
      with acetylcholine and with noncompetitive agonists suggested that all PC12 cell
      nicotinic acetylcholine receptor subtypes that respond to acetylcholine also
      respond to noncompetitive agonist. The action of noncompetitive agonists
      therefore seems to be highly conserved between nicotinic acetylcholine receptor
      subtypes, in agreement with the high level of structural conservation in the
      sequence region harboring major elements of this site.

PMID- 7589217
TI  - Staurosporine inhibits inositol phosphate formation in bovine adrenal medullary
      cells.
AB  - The effect of protein kinase C activators and inhibitors on histamine-stimulated
      phospholipase C in bovine adrenal medullary cells has been investigated. The
      protein kinase C activators, phorbol 12,13-dibutyrate (PDB) or sn-1,2
      dioctanoylglycerol (DOG), inhibited histamine-stimulation of phospholipase C.
      This inhibition was prevented by the protein kinase C-selective inhibitor Ro 31
      8220 (3-[1-[3-(2-isothioureido) propyl]indol-3-yl]-4-(1-methylindol-3-yl)-3
      pyrrolin-2,5-dio ne) but not the broad spectrum protein kinase inhibitor
      staurosporine. Indeed staurosporine on its own inhibited both the histamine
      stimulated response and, in permeabilized cells, phospholipase C activated by
      Ca2+. Staurosporine inhibition of phospholipase C is unlikely to be mediated via
      protein kinase A or Ca2+/calmodulin-dependent protein kinase because it was not
      reproduced by selective inhibition of these kinases. Staurosporine treatment,
      however, reduced inositol phospholipid levels in stimulated cells. Thus
      staurosporine and Ro 31-8220, two widely used protein kinase C inhibitors, have
      quite different effects on phospholipase C activation. Furthermore, staurosporine
      may cause this inhibition through a reduction in the level of phospholipase C
      substrate.

PMID- 7589216
TI  - Allosteric modulation of the glutamate site on the NMDA receptor by four novel
      glycine site antagonists.
AB  - Using radioligand binding studies, we have investigated the binding properties of
      four 4-hydroxy-2-quinolones, a novel series of selective antagonists for the
      glycine site on the N-methyl-D-aspartate (NMDA) receptor. L-701,324, L-703,717, L
      698,532 and L-695,902 inhibited [3H]L-689,560 (glycine site antagonist) binding
      to rat cortex/hippocampus P2 membranes with IC50 values of 1.97, 4.47, 209 and
      6448 nM, respectively, whilst also inhibiting non-equilibrium [3H]dizocilpine
      binding to the NMDA receptor ion-channel. All four compounds partially inhibited
      L-[3H]glutamate (approximately 50% inhibition; agonist) binding and enhanced
      [3H]cis-4-phosphonomethyl-2-piperidine carboxylate ([3H]CGS-19755; 41-81%
      enhancement; 'C-5' antagonist) and [3H]3-(2-carboxypiperazin-4-yl)-propyl-1
      phosphonate ([3H]CPP; 28-66% enhancement; 'C-7' antagonist) binding to the
      glutamate recognition site of the NMDA receptor with EC50 values similar to those
      observed for [3H]L-689,560 binding. These results provide further evidence for
      allosteric interactions between the glutamate and glycine recognition sites of
      the NMDA receptor complex, and as the 4-hydroxy-2-quinolones are 'full'
      antagonists at the glycine site, indicate that these interactions are not caused
      by the intrinsic activity of a compound.

PMID- 7589220
TI  - Time course of phorbol ester-induced contraction and protein kinase C activation
      in rat aorta.
AB  - This study investigates the relationship between the rate of phorbol ester
      induced contraction of intact rat aorta and protein kinase C activation, as
      assessed by the translocation of protein kinase C from the cytosolic to the
      particulate fraction. Aorta was exposed to Ca(2+)-free physiologic salt solution
      prior to phorbol ester to prevent Ca(2+)-induced protein kinase C translocation
      during tissue homogenization. Phorbol myristate acetate, as well as phorbol
      dibutyrate, decreased cytosolic and/or increased particulate protein kinase C
      activity as early as 5 s following phorbol ester addition, which was prior to, or
      coincident with, the onset of contraction. These results suggests that phorbol
      ester-induced contraction of intact vascular smooth muscle is associated in a
      time-dependent manner with protein kinase C activation.

PMID- 7589218
TI  - Stable expression and pharmacological properties of the human alpha 7 nicotinic
      acetylcholine receptor.
AB  - The alpha 7 neuronal nicotinic acetylcholine receptor subtype forms a Ca(2+)
      permeable homooligomeric ion channel sensitive to alpha-bungarotoxin in Xenopus
      oocytes. In this study, we have stably and functionally expressed the human alpha
      7 cDNA in a mammalian cell line, HEK-293 and examined its pharmacologic
      properties. [125I] alpha-Bungarotoxin bound to transfected cells with a Kd value
      of 0.7 nM and a Bmax value of 973 pmoL/mg protein. No specific binding was
      detected in untransfected cells. Specific binding could be displaced by unlabeled
      alpha-bungarotoxin (Ki = 0.5 nM) and an excellent correlation was observed
      between binding affinities of a series of nicotinic cholinergic ligands in
      transfected cells and those in the human neuroblastoma IMR-32 cell line.
      Additionally, cell surface expression of alpha 7 receptors was detected by
      fluorescein isothiocyanate-conjugated alpha-bungarotoxin in transfected cells.
      Whole cell currents sensitive to blockade by alpha-bungarotoxin, and with fast
      kinetics of activation and inactivation, were recorded from transfected cells
      upon rapid application of (-)-nicotine or acetylcholine with EC50 values of 49
      microM and 155 microM respectively. We conclude that the human alpha 7 subunit
      when expressed alone can form functional ion channels and that the stably
      transfected HEK-293 cell line serves as a unique system for studying human alpha
      7 nicotinic receptor function and regulation, and for examining ligand
      interactions.

PMID- 7589219
TI  - Effects of methylene blue and LY83583 on neuronal nitric oxide synthase and NADPH
      diaphorase.
AB  - Methylene blue and 6-anilino-5,8-quinolinedione (LY83583) have often been used as
      'selective' inhibitors of soluble guanylyl cyclase. We report that in in vitro
      assays, both these compounds were potent inhibitors of rat cerebellar nitric
      oxide synthase activity. Methylene blue had an apparent Ki of 2.7 microM, while
      for LY83583 the Ki was 15.8 microM. Furthermore, methylene blue, but not LY83583,
      inhibited the NADPH-diaphorase histochemical reaction associated with nitric
      oxide synthase. Our results indicate that many of the effects of these drugs
      which have been attributed to inhibition of guanylyl cyclase, may derive from
      their direct inhibition of nitric oxide synthase activity instead.

PMID- 7589221
TI  - [3H]N-methylscopolamine dissociation from muscarine receptors affected by low
      concentrations of allosteric modulators.
AB  - The ability of allosteric ligands to modulate the dissociation rate of [3H]N
      methylscopolamine from atrial muscarinic receptors in the presence of varying
      concentrations of unlabelled N-methylscopolamine or atropine was evaluated.
      Gallamine, at a concentration approximating its KD value, slowed the dissociation
      of [3H]N-methylscopolamine in the presence of ca. 30 x KD of both unlabelled NMS
      or atropine. This was less evident when concentrations of ca. 1000 x KD of the
      unlabelled antagonists were employed. Similar findings were made with another
      allosteric modulator. These results indicate that gallamine can act
      allosterically at low concentrations.

PMID- 7589222
TI  - Chronic fluoxetine or desmethylimipramine treatment alters 5-HT2 receptor
      mediated c-fos gene expression.
AB  - These studies examined the effects of a 21-day treatment regime with either the
      tricyclic antidepressant, desmethylimipramine (DMI), or the selective 5-HT uptake
      inhibitor, fluoxetine, on 5-HT2 receptors in rat brain, as assessed by selective
      agonist-mediated c-fos gene expression. Chronic, but not acute, treatment with
      fluoxetine (10 mg/kg, i.p. for 21 days) resulted in supersensitization of the
      response to an acute challenge (4 mg/kg, i.p.) with the selective 5-HT2 agonist,
      2,5-dimethoxy-4-iodoamphetamine (DOI), both in frontal cortex and in hippocampus.
      Chronic treatment with DMI (10 mg/kg, i.p. for 21 days) resulted in a significant
      desensitization of the response to DOI. These findings are discussed in relation
      to the possible modes of action of these two clinically useful agents.

PMID- 7589224
TI  - Localization of [125I]endothelin-1 in injured aorta of rabbits.
AB  - Endothelin-1 is a potent vasoconstrictor. This study was performed to determine
      whether arterial injury, induced by either hypercholesterolemia or mechanical
      disruption of the endothelium, is associated with increased localization of
      endothelin-1 in the artery. The blood clearance and tissue distribution of
      intravenously injected [125I]endothelin-1 was evaluated in 33 rabbits--control
      animals (n = 7), balloon de-endothelialized animals (n = 12), cholesterol-fed
      animals (n = 6) and animals that had both balloon de-endothelialization and high
      cholesterol diet (n = 8). The blood clearance half time was less than 10 min,
      with slightly slower clearance in the ballooned/cholesterol-fed animals.
      [125I]Endothelin-1 localized in the lung (approximately 12% injected dose
      (ID)/organ) and kidney (approximately 8%ID/organ). [125I]Endothelin-1
      localization in the injured aorta increased from the baseline level of
      0.06%kgID/g to its highest level within 5 min of balloon de-endothelialization
      (0.2%kgID/g) and decreased to 0.11%kgID/g within one week and remained
      essentially unchanged through 16 weeks. The area with increased binding of
      [125I]endothelin-1 corresponded to the zone of arterial injury stained with Evans
      blue. On the other hand, the binding in the aorta did not increase with the
      atherogenic diet. These findings suggest that endothelin-1 accumulates in injured
      vessels, attaining the highest levels immediately after mechanical injury.

PMID- 7589223
TI  - Methylmercury induces Ca(2+)-dependent hyperpolarization of mouse thymocytes: a
      flow cytometric study using fluorescent dyes.
AB  - The effect of methylmercury on mouse thymocytes was examined using fluorescent
      dyes for membrane potential and intracellular Ca2+. Methylmercury at
      concentrations of 1 microM or higher (up to 30 microM) produced hyperpolarization
      in a dose-dependent fashion. Charybdotoxin and quinine, but not 4-aminopyridine
      and tetraethylammonium, greatly suppressed methylmercury-induced
      hyperpolarization. Removal of external Ca2+ reduced the degree of
      hyperpolarization. Pretreatment of thymocytes with A23187 under Ca(2+)-free
      conditions abolished the hyperpolarization induced by methylmercury. Under both
      normal and Ca(2+)-free conditions methylmercury increased the intracellular
      concentration of Ca2+. The results suggest that the increase in intracellular
      Ca2+ is mediated through a Ca2+ release from intracellular stores as well as
      through influx of external Ca2+. Therefore, it is likely that methylmercury
      increases the intracellular concentration of Ca2+, resulting in activation of
      Ca(2+)-dependent K+ conductance of mouse thymocytes.

PMID- 7589225
TI  - Alterations in plasma tryptophan binding to albumin in 2,3,7,8-tetrachlorodibenzo
      p-dioxin-treated Long-Evans rats.
AB  - We have previously shown that the wasting syndrome in response to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) administration is associated with a specific
      increase in free tryptophan (unbound to albumin) in rats. The present series of
      experiments was undertaken to characterize how the binding of tryptophan to
      albumin is altered by TCDD and to find the underlying cause of the changes. TCDD
      administered to Long-Evans rats proved to diminish the maximal binding capacity
      (Bmax) of albumin for tryptophan by ca. 60% without any marked change in the
      binding affinity. Of candidate mediating factors, neither TCDD nor bilirubin
      affected the binding equilibrium of tryptophan with albumin in vitro. However, a
      mixture of free fatty acids greatly increased the proportion of free tryptophan
      at physiologically relevant concentrations. Similarly, the free fatty acid
      mixture added to plasma in vitro decreased only Bmax of albumin in a manner
      similar to the effect of TCDD administered in vivo. Extraction of lipid-soluble
      substances from the plasma with ether was effective in reversing the increase in
      free tryptophan in the plasma of TCDD-treated rats while dialysis of water
      soluble substances was not. Ether extraction also resulted in a decrease in free
      fatty acids. We conclude that disturbances in lipid metabolism may be involved in
      the pathogenesis of TCDD-induced alterations in tryptophan binding to albumin in
      vivo.

PMID- 7589226
TI  - Stable expression of human cytochrome P450 2E1 in V79 Chinese hamster cells.
AB  - A V79 Chinese hamster cell line was constructed for stable expression of human
      cytochrome P450 2E1 (CYP2E1) by integration of a SV40 Early promoter recombinant
      CYP2E1 cDNA into the chromosomal DNA. The cDNA encoded CYP2E1 was effectively
      expressed and enzymatically active, as shown by hydroxylation of chlorzoxazone
      and of p-nitrophenol, at rates of about 70 pmol x mg-1 total protein x min-1.
      CYP2E1 content and activity was increased upon cultivation in the presence of
      ethanol indicating a substrate mediated stabilization effect. A similar
      stabilizing effect was also observed for inhibitors of CYP2E1, e.g. imidazole, 4
      methylpyrazole, and isoniazid. The feasibility of the newly established cell line
      V79MZh2E1 for toxicological studies was shown by CYP2E1-mediated activation of N
      nitrosodimethylamine and p-nitrophenol and a dose-dependent cytotoxic and
      mutagenic effect.

PMID- 7589227
TI  - Inhibitory effects of cadmium ion on extracellular Ca(2+)-independent contraction
      of rat aorta.
AB  - In vitro effects of cadmium ion on vasoconstriction, particularly on
      vasoconstriction independent of extracellular Ca2+, were investigated using
      isolated rat aorta. Aorta incubation with CdCl2 (0.01, 0.1 mM) significantly
      attenuated contractile responses to KCl and phenylephrine in the medium
      containing normal Ca2+ (2.5 mM). The contractile response to phenylephrine in the
      presence of calcium channel antagonists, nifedipine (1 microM) or verapamil (1
      microM), was markedly inhibited by CdCl2 (0.1 mM). In the medium without Ca2+,
      phenylephrine (10 microM) induced a phasic contraction, which was markedly
      inhibited by CdCl2 (0.1 mM). In the medium without Ca2+, phorbol 12-myristate 13
      acetate (1 microM) and okadaic acid (10 microM) caused tonic contractile
      responses, which were strongly attenuated by CdCl2 (0.1 mM) pretreatment.
      Contractile response to sodium fluoride (5 approximately 15 mM) in the absence of
      extracellular Ca2+ was strongly attenuated by CdCl2 (0.1 mM) pretreatment. These
      results suggest that cadmium ion depresses an extracellular Ca(2+)-independent
      component of agonist-induced vasoconstriction by hindering an intracellular
      contractile mechanism(s).

PMID- 7589229
TI  - Chronopharmacological study of acetylsalicylic acid in mice.
AB  - Influence of dosing time on pharmacological effects and toxicity of
      acetylsalicylic acid was investigated in ICR male mice under light-dark (12:12)
      cycle. Significant circadian rhythms (day-night rhythms) were demonstrated for
      hypothermal and analgesic effects at 1 h after an injection of acetylsalicylic
      acid (200 mg/kg, i.p.) (P < 0.01, respectively). The rhythmic patterns of
      acetylsalicylic acid induced analgesia and hypothermia resembled overall the
      rhythms occurring in the non-drugged state. Injection of acetylsalicylic acid
      resulted in a parallel increase in latency to hot plate and a parallel decrease
      in rectal temperature. The relationship between plasma salicylate concentrations
      and responses was not clear. There was also a significant circadian rhythm in
      acetylsalicylic acid (850 mg/kg, i.p.) induced toxicity with the highest
      mortality at 17:00 and the lowest one at 05:00 (P < 0.05). Dosing time dependent
      kinetics of salicylate seems to be related to the rhythm of toxicity of the drug.
      The time in circadian stage at which acetylsalicylic acid is administered is
      essentially important in the actions of acetylsalicylic acid.

PMID- 7589228
TI  - The biochemical effects of clenbuterol: with particular reference to taurine and
      muscle damage.
AB  - Administration of clenbuterol to rats in the drinking water over a 4 day period
      increased incorporation of [3H]leucine into muscle protein and caused a slight
      reduction in urinary 3-methylhistidine but did not result in an increase in body
      or muscle weight. However, both urinary and liver taurine were significantly
      reduced at the highest dose of clenbuterol (2 mg.kg-1.day-1). Serum creatine
      kinase, muscle isoenzyme (CK-MM) was raised and single muscle fibre injury was
      observed in the soleus muscle in animals treated with the middle dose (0.2 mg.kg
      1.day-1) and highest dose (2 mg.kg-1.day-1). The reduction in the body pool of
      taurine caused by clenbuterol is of concern as taurine has been shown to have
      protective properties.

PMID- 7589230
TI  - Bioallethrin causes permanent changes in behavioural and muscarinic acetylcholine
      receptor variables in adult mice exposed neonatally to DDT.
AB  - We recently reported changes in the density of muscarinic acetylcholine receptors
      in cerebral cortex of mice treated neonatally with DDT (1,1,1-trichloro-2,2-bis(p
      chlorophenyl)-ethane) and receiving bioallethrin as adults. We also found
      behavioural aberrations in adult mice treated with bioallethrin, whether
      neonatally treated with DDT or the vehicle. To ascertain whether these changes
      were permanent, 10-day-old mice received an oral dose of DDT (0.5 mg/kg body
      weight) and at the age of 5 months they received bioallethrin orally (0.7 mg/kg
      body weight/day; 7 days). The animals were investigated at the age of 7 months.
      Here we report muscarinic acetylcholine receptor changes, additional behavioural
      disturbances and learning disabilities in mice receiving DDT as neonates and
      bioallethrin as adults, whereas the behavioural disturbances in mice receiving
      vehicle as neonates and bioallethrin as adults had diminished and changes in
      proportions of high- and low-affinity binding sites had developed. No changes in
      the density of nicotinic acetylcholine receptors were noted for any of the
      treated groups. In conclusion, exposure of neonates to DDT leads to increased
      susceptibility in adults to a short-acting pesticide with similar neurotoxic
      action. An adult exposure to this short-acting pesticide to mice neonatally
      exposed to DDT leads to irreversible muscarinic acetylcholine receptor changes
      and behavioural disturbances with additional changes 2 months after the exposure.

PMID- 7589231
TI  - Triethyllead decreases central benzodiazepine receptor binding in rat cerebellum
      ex vivo.
AB  - Effect of triethyllead on the specific [3H]flunitrazepam binding was studied in
      rat cortical and cerebellar P2 fractions in vitro and in tissue homogenates of
      several rat brain regions ex vivo after 5 daily subcutaneous doses of 1.9 mg/kg
      triethyllead acetate to rats. Up to concentration of 100 microM, triethyllead did
      not affect significantly the specific [3H]flunitrazepam binding but attenuated
      marginally (14-18%) the GABAA receptor agonist, muscimol-induced elevation of
      [3H]flunitrazepam binding in cerebellar tissue. After the subacute treatment of
      rats with triethyllead, the specific [3H]flunitrazepam binding was 27% lower in
      cerebellum compared to control animals. In other brain regions the receptor
      binding was not changed. The data suggest that triethyllead modified the
      cerebellar GABAA receptor complex causing decreased binding in the benzodiazepine
      site. Such an inhibitory effect in the GABAA receptor complex may decrease
      cerebellar inhibitory output and augment the triethyllead induced convulsions and
      tremor.

PMID- 7589232
TI  - Activation of benzylic alcohols to mutagens by rat and human sulfotransferases
      expressed in Escherichia coli.
AB  - Human hydroxysteroid sulfotransferase, human phenol-sulfating form of phenol
      sulfotransferase, rat hydroxysteroid sulfotransferase a and rat phenol
      sulfotransferase IV were expressed in Escherichia coli. Cytosol preparations of
      transformed bacteria were used as activating systems in mutagenicity tests with
      Salmonella typhimurium TA98. All test compounds, 1-hydroxymethylpyrene, 2
      hydroxymethylpyrene, 1-(1-pyrenyl)ethanol, 9-hydroxymethylanthracene, 7
      hydroxymethyl-12-methylbenz[a]anthracene and 4H-cyclopenta[def]chrysen-4-ol, were
      activated by both hydroxysteroid sulfotransferases investigated. However, 1-(1
      pyrenyl)ethanol was 67-fold more efficiently activated by the human enzyme,
      whereas 7-hydroxymethyl-12-methylbenz[a]anthracene was 27-fold more efficiently
      activated by the rat enzyme. The phenol sulfotransferases showed relatively low
      activities with the benzylic alcohols investigated. The only exception was 4H
      cyclopenta[def]chrysen-4-ol, which was activated efficiently by rat phenol
      sulfotransferase IV. We had previously tested the ability of rat and human
      hepatic cytosol preparations to activate the same compounds. The results of a
      statistical analysis suggest that the activities of human hydroxysteroid
      sulfotransferase, rat hydroxysteroid sulfotransferase a and phenol
      sulfotransferase IV can account for a substantial portion of the activation of
      benzylic alcohols in human, female rat and male rat liver, respectively.

PMID- 7589233
TI  - Protective effect of cell-permeable ceramide analogs against modeccin, ricin,
      Pseudomonas toxin, and diphtheria toxin.
AB  - We investigated the effects of various ceramide (Cer) analogs and related
      sphingolipids on the cytotoxicities of modeccin, ricin, Pseudomonas toxin, and
      diphtheria toxin in various cell lines. The most pronounced protective effect by
      C6Cer, a short-chain cell-permeable Cer analog, was observed in modeccin
      cytotoxicity in Vero, BER-40, and MDCK cells, whereas the cytotoxicity of
      diphtheria toxin was not affected by any of the ceramide analogs tested. C6Cer
      did not affect the binding and internalization of ricin and modeccin in Vero and
      BER-40 cells. C2Cer and C8Cer also protected against modeccin cytotoxicity,
      albeit less effectively than C6Cer. However, related sphingolipids including
      sphingosine, sphingomyelin, lactosylceramide, C18Cer (the naturally occurring
      ceramide), and dihydro C6Cer had no effect. A correlation was found between the
      ability of ceramides to inhibit bulk protein secretion and the inhibition of
      modeccin cytotoxicity by ceramides. Among Cer analogs tested, C6Cer, the most
      potent inhibitor of modeccin cytotoxicity, strongly inhibited bulk protein
      secretion in Vero, BER-40, and MDCK cells. PtK1 cells, which were not protected
      by ceramides against toxins, were resistant to ceramide-induced inhibition of
      bulk protein secretion. These results confirm that Cer may modulate the
      intracellular transport of proteins through the Golgi complex. Such Cer-sensitive
      processes may be involved in the intoxication of cells by plant and bacterial
      toxins, especially modeccin.

PMID- 7589234
TI  - Activation of multiple transcription factors and fos and jun gene family
      expression in cells exposed to a single electric pulse.
AB  - We report that exposure of cells to a single electric pulse (250-1250 V/cm)
      results in the rapid and persistent activation of the DNA binding activities of a
      number of transcription factors, including AP-1, SP1, AP-2, and NF-kappa B, and
      the transient expression of select members of the fos and jun gene families.
      Induction of gene expression occurs primarily at the level of transcription,
      although c-jun expression also appears to be regulated posttranscriptionally.
      Interestingly, maximal induction of gene expression is detected at electrical
      field strengths that do not result in pore formation in the plasma membrane and
      that do not significantly affect cell viability. Exposure of cells to electric
      pulses does not result in the activation of HSF1 DNA binding activity, or the
      induction of hsp70 or p53 protein synthesis, indicating that the induction of fos
      and jun gene expression is not coincident with protein or DNA damage. The results
      of these studies suggest that electrical pulses may represent a novel mechanism
      for inducing the activities of multiple transcription factors and the expression
      of select members of the fos and jun gene families.

PMID- 7589235
TI  - Rat HPC-1/syntaxin 1A and syntaxin 1B interrupt intracellular membrane transport
      and inhibit secretion of the extracellular matrix in embryonic cells of an
      amphibian.
AB  - HPC-1/syntaxin 1A and syntaxin 1B are proteins that have been implicated in the
      docking and/or fusion of synaptic vesicles to the presynaptic plasma membrane in
      neural cells. Capped RNAs (cRNAs) for rat HPC-1 and syntaxin 1B were injected
      into embryonic cells of an amphibian, the Japanese newt. The effects of the
      proteins translated from the injected cRNAs on intracellular membrane transport
      and secretion of the extracellular matrix (ECM) were then investigated.
      Immunoblotting and immunoelectron microscopy showed that the HPC-1 synthesized in
      the embryonic cells was localized on the membranes of Golgi complexes and
      vacuoles and on the plasma membrane. Electron microscopy revealed the
      morphological deformation of Golgi complexes, an appearance of large number of
      vacuoles, and the disappearance of the ECM from the cell surface in the cRNA
      injected embryos. The results showed that HPC-1 and syntaxin 1B interrupt the
      pathways of intracellular membrane transport and inhibit the secretion of ECM by
      amphibian embryonic cells. Similar mechanisms may be involved in regulation of
      the secretory process of synaptic vesicles in mammalian neural cells and in
      regulation of intracellular membrane transport and constitutive secretion of ECM
      in amphibian embryonic cells.

PMID- 7589236
TI  - Components of the nucleolar processing complex (Pre-rRNA, fibrillarin, and
      nucleolin) colocalize during mitosis and are incorporated to daughter cell
      nucleoli.
AB  - We have traced in onion root cells the mitotic course of rRNA, of the RNA
      synthesized in the G2 period of the preceding interphase, and of the nucleolar
      proteins fibrillarin and nucleolin. The rRNA was detected by ultrastructural in
      situ hybridization with a rDNA probe capable of hybridizing mature rRNAs and also
      the intermediate forms of pre-rRNA processing. The RNA synthesized in the
      preceding G2 (which, according to classical data, is mostly rRNA) was revealed by
      autoradiography on synchronous cells labeled in G2 by tritiated uridine.
      Fibrillarin was detected by immunofluorescence in both mammalian and onion cells;
      the results in the latter cells were compared with those obtained after AgNOR
      staining. Electron microscopical immunocytochemistry was used to detect
      fibrillarin and nucleolin in onion cells. In all cases, following nucleolar
      dispersion in prophase, the signal was detected in the chromosome periphery
      during metaphase and anaphase, in irregular fibrillar masses located between
      chromosomes in ana-telophase, in prenucleolar bodies during telophase, and in the
      newly formed nucleoli, after nucleologenesis. Moreover, as expected, ribosomes
      appeared labeled after in situ hybridization, but a dispersed cytoplasmic
      labeling was observed in all experiments, mainly during metaphase and anaphase.
      These results demonstrate that nucleolar components involved in pre-rRNA
      processing, including rRNA itself, probably in an incompletely processed form,
      are transferred from the parental to the daughter cell nucleoli by means of
      transient structures, such as the perichromosomal sheath and prenucleolar bodies.
      Since these macromolecular components are assembled in the interphase nucleolus,
      forming the RNP processing complex, their colocalization during mitosis in the
      same transient structures strongly suggests that at least a subset of these
      complexes does not disaggregate during cell division, but remains assembled and
      becomes incorporated to the new nucleolus. Therefore, ribosome biogenesis
      restarts not only after mitosis at the level of transcription, but also at the
      intermediate levels of pre-rRNA processing.

PMID- 7589237
TI  - Increased expression of p21Sdi1 in adrenocortical cells when they are placed in
      culture.
AB  - Expression of the cell cycle inhibitor p21Sdi1/WAF1/Cip1 was investigated in a
      differentiated cell type, the adrenocortical cell, at different stages of
      culture, from the preparation of cells from the adrenal gland to senescence after
      long-term growth. In bovine adrenocortical cells, expression of SDI1 was much
      higher in culture than in vivo. Elevation of SDI1 mRNA, accompanied by elevation
      of the level of a protein reacting with anti-p21Sdi1 antibodies, was observed as
      early as 3 h after the start of the tissue dissociation procedure used to prepare
      cells for culture. This level of expression was then maintained during plating
      and subsequent long-term growth in culture. Growth and quiescence in bovine
      adrenocortical cells can be modulated by inclusion or removal of FGF from the
      culture medium. In these cells SDI1 mRNA was not increased by long-term mitotic
      quiescence resulting from FGF deprivation. In cultured fetal human adrenocortical
      cells, SDI1 mRNA was also detected at all stages of the culture life span,
      including 2 days after isolation of cells from the adrenal gland and plating in
      culture. Mid-life-span cells had higher SDI1 mRNA than senescent human
      fibroblasts. Clones of human adrenocortical cells nearing senescence in culture
      had somewhat higher SDI1 mRNA than early passage cells. Thus, SDI1 expression in
      adrenocortical cells is not associated with mitotic quiescence either in vivo or
      in vitro, yet isolation of the cells and culturing them exerts a powerful
      inductive influence on its expression.

PMID- 7589238
TI  - Localization of utrophin and aciculin at sites of cell-matrix and cell-cell
      adhesion in cultured cells.
AB  - Aciculin is a phosphoglucomutase-related cytoskeletal protein associated with
      dystrophin and/or utrophin in various tissues and cell types. Comparison of
      expression patterns for aciculin, dystrophin, and utrophin in cultured cells
      demonstrated that aciculin is coexpressed with utrophin, but not with dystrophin,
      in cultures of A7r5 smooth muscle cells and REF52 fibroblasts. Some other
      nonmuscle cells synthesized only trace levels of or no aciculin and utrophin.
      Aciculin was detected by immunoblotting in antiutrophin immunoprecipitates from
      A7r5 and REF52 cultured cells, indicating an association between these two
      proteins. The aciculin-utrophin complex in fibroblasts and smooth muscle cells
      was mostly resistant to Triton X-100 extraction and was detected predominantly in
      the Triton-insoluble fraction, enriched in actin and actin-associated proteins.
      By immunofluorescence both aciculin and utrophin were identified in a similar dot
      like or streak-like pattern in A7r5 and REF52 cultured cells. Immunolocalization
      of utrophin in cultured fibroblasts and smooth muscle cells in combination with
      interference reflection microscopy demonstrated that utrophin staining was mostly
      codistributed, but not exclusively confined to the areas of focal adhesions,
      sites of closest cell attachment to the substrate. Double immunostaining of A7r5
      and REF52 cells for aciculin and utrophin revealed a precise colocalization of
      both cytoskeletal proteins at focal adhesions and along microfilaments.
      Costaining of cultured fibroblasts and smooth muscle cells with antibodies
      against utrophin and major focal adhesion components, vinculin and talin, showed
      that utrophin is concentrated in focal adhesions both at initial stages of cell
      spreading and in well spread cells of nearly confluent monolayers. In MCF10
      breast epithelial cells both utrophin and aciculin were localized at cell-cell
      adherens-type junctions. Our data show that utrophin is a cytoskeletal component
      of cell-matrix and cell-cell adhesions in various cultured cells. In certain cell
      types the aciculin-utrophin complexes may contribute to the linking actin
      filaments to the plasma membrane.

PMID- 7589240
TI  - Myristoylation is required for the intracellular localization and endocytic
      function of ARF6.
AB  - ADP-ribosylation factors (ARFs) are modified by a myristate group that is
      covalently linked to the second glycine residue at the amino terminus. With the
      recent evidence that ARF6 localizes to the cell periphery and plays a regulatory
      role in endocytic traffic, we have investigated the role of myristoylation on the
      membrane association, biological activity, and subcellular distribution of ARF6
      in intact cells. A Gly2Ala mutation produced a nonmyristoylated protein that
      failed to associate with membranes, was cytosolic, and had no effect on endocytic
      transport. To determine if a different form of lipid modification could restore
      membrane association and biological activity, a nonmyristoylated ARF6 derivative
      was constructed that contained a prenyl group at the carboxy terminus. Prenylated
      ARF6 bound efficiently to membranes, but had no effect on receptor-mediated
      endocytosis and was mislocalized to distinct intracellular structures. Thus,
      although prenylation can replace myristoylation for membrane association, the
      latter appears to be critical for the proper targeting and biological activity of
      ARF6.

PMID- 7589239
TI  - p125FAK tyrosine phosphorylation and focal adhesion assembly: studies with
      phosphotyrosine phosphatase inhibitors.
AB  - p125FAK is a major tyrosine kinase phosphorylated in response to integrin
      dependent adhesion. In this study we use vanadate and phenylarsine oxide (PAO),
      known inhibitors of phosphotyrosine phosphatases (PTPases), as a tool to
      artificially modulate p125FAK phosphorylation in human endothelial and in Chinese
      hamster ovary cells. Vanadate treatment strongly upregulates in a dose-dependent
      manner the level of tyrosine phosphorylation of several proteins in adherent
      cells. PAO induces a more restricted profile of tyrosine-phosphorylated proteins,
      increasing primarily a broad band of 120-140 kDa. Maximal stimulation of p125FAK
      tyrosine phosphorylation is reached at 10 microM PAO. In contrast, in vanadate
      treated cells the p125FAK tyrosine phosphorylation shows a biphasic curve, being
      increased at high doses of vanadate (100 microM) and downregulated at low doses
      (25 microM). Immunofluorescence analysis of cells treated with PTPase inhibitors
      showed a direct correlation between the level of p125FAK tyrosine phosphorylation
      and the assembly of focal adhesions and actin stress fibers. Downregulation of
      p125FAK tyrosine phosphorylation is observed by treating cells with cytochalasin
      D (CD), a drug known to rapidly disrupt the actin cytoskeleton. When PTPase
      inhibitors are added in combination to CD, the level of tyrosine phosphorylation
      of p125FAK remains high and focal adhesions and actin stress fibers are preserved
      from the CD-mediated disruption. Based on these data we suggest that assembly of
      actin cytoskeleton plays an important role in inhibiting PTPases involved in
      p125FAK tyrosine phosphorylation.

PMID- 7589241
TI  - Intercellular heterogeneity of early mitogenic events: cAMP generalizes the EGF
      effect on c-Fos protein appearance but not on MAP kinase phosphorylation and
      nuclear translocation in dog thyroid epithelial cells.
AB  - When quiescent dog thyroid epithelial cells in primary culture are stimulated for
      48 h with thyrotropin (TSH), forskolin acting through cAMP, or with cAMP
      independent mitogens including epidermal growth factor (EGF), hepatocyte growth
      factor (HGF), and a tumor promoting phorbol ester (TPA), only 30-60% of cells
      progress through the cell cycle. A more general growth response requires the
      combination of EGF and TSH or forskolin. In this study we ask whether this
      intercellular heterogeneity in mitogen sensitivity could depend on a similar
      heterogeneity at early stages of the mitogenic stimulation process, i.e., at the
      levels of p42/p44 MAP kinase nuclear translocation and c-Fos protein appearance.
      We used indirect immunofluorescence microscopy with photometric quantitation and
      corroborated data using Western blotting. We analyzed the double staining of c
      Fos and p42/p44 MAP kinases, since the nuclear translocation of these MAP kinases
      has been suggested as a key step for the stimulation of c-fos transcription. (i)
      EGF and HGF induced c-Fos accumulation and MAP kinase translocation in variable
      fractions of the cell population that corresponded to their relative potency as
      mitogens. c-Fos appearance and MAP kinase translocation poorly correlated in
      individual cells. Many cells accumulated c-Fos without any detectable p42/p44 MAP
      kinase translocation. The heterogeneity of proliferative responses to EGF could
      be due to the lack of c-Fos or MAP kinase responsiveness of many cells. (ii) TPA
      induced c-Fos accumulation and MAP kinase translocation within the whole cell
      population, which did not explain the heterogeneity of the growth response to
      this factor and showed that these events are not sufficient to elicit DNA
      synthesis, (iii) TSH and forskolin induced a weak c-Fos accumulation in only a
      minority of cells but, as previously shown, no p42/p44 MAP kinase phosphorylation
      and translocation. An important c-Fos expression was thus dispensable for the
      strong DNA synthesis stimulation exerted by cAMP-dependent mitogens. (iv)
      Forskolin potentiated the EGF effect on c-Fos expression but not on p42/p44 MAP
      kinase phosphorylation and translocation. This reflected the fact that EGF
      induced c-Fos accumulation in 90% of cells in the presence of forskolin but in 30
      50% of cells in its absence. This kind of potentiation, which specifically
      implies an increase in the fraction of responding cells, is termed
      "generalization" in the present study.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7589242
TI  - Nuclear translocation of beta II PKC isoenzyme in phorbol ester-stimulated KM-3
      pre-B human leukemic cells.
AB  - Members of the protein kinase C (PKC) family play a key role in regulating cell
      growth and differentiation in response to several stimuli, including hormones,
      neurotransmitters, and growth factors. The different properties and substrate
      specificity of the PKC isoforms are not fully understood, and they are assumed to
      have specific functions in intracellular signaling. In lymphoid cells, the
      effects of PMA and Ca2+ ionophore, singly or in combination, on activation and
      expression of Ca(2+)-dependent PKC at the level of protein and messenger RNA have
      been examined. Starting from these observations and the possibility that
      differential isoenzyme expression might contribute to the differences in phorbol
      ester sensitivity of lymphoid cells, it seemed worthwhile to investigate the
      expression and the modulation of PKC isoforms in KM-3 cells, a human pre-B cell
      line, upon treatment with phorbol 12-myristate 13-acetate (PMA). Using
      multiparametric analysis we detected three PKC isoforms in the KM-3 cell line:
      alpha, beta II, and zeta. PMA treatment causes an intranuclear translocation of
      the beta II isoform, via the nuclear pore complex, associated with the
      interchromatinic regions. These data suggest that the beta II isoenzyme may play
      a strategic role in signal transduction and regulation of specific gene
      expression in B lymphocytes.

PMID- 7589244
TI  - Cell type-specific expression of hnRNP proteins.
AB  - HnRNP proteins are abundant nucleoplasmic pre-mRNA-binding proteins which have
      important roles in the biogenesis of mRNA. Although hnRNP proteins have been
      extensively characterized in cultured cell lines, little is known about their
      expression in animal tissues. Here, we have undertaken a systematic survey of the
      expression of major hnRNP proteins in mouse tissue using specific monoclonal
      antibodies. Immunohistochemical staining demonstrated that hnRNP proteins C, L,
      and U were localized to nuclei in all tissues examined. However, cytoplasmic
      expression of hnRNP A1, D, F/H, and K was also detected in several tissues,
      suggesting that these proteins have roles in the cytoplasm as well as the
      nucleus. Importantly, the relative amounts of different hnRNP proteins varied
      among cell types. This was especially striking in neuronal and reproductive
      cells. In the brain, certain neuronal cell types contained more hnRNP proteins
      than glial cells, perhaps reflecting increased levels of neuronal transcription
      and RNA processing. In the ovary, oocytes contained exceptionally high
      concentrations of hnRNP proteins as compared to follicular and stromal cells. In
      the testis, the expression of hnRNP proteins was generally high and was found to
      be tightly regulated during spermatogenesis. Specifically, hnRNP A1 was highly
      expressed only in early spermatogonia and absent in later stages. These findings
      demonstrate that hnRNP proteins do not exist in a fixed stoichiometry across
      different cell types. Furthermore, as the relative amounts of pre-mRNA-binding
      proteins (e.g., A1 and ASF/SF2) can affect alternative splicing patterns, the
      variations that we have observed could profoundly affect cell-specific gene
      expression.

PMID- 7589243
TI  - Insulin-like growth factor-II as a paracrine growth factor in human neuroblastoma
      cells.
AB  - The human neuroblastoma line, SK-N-SH, has been subcloned into SH-SY5Y, a
      neuroblast N cell line, and SH-EP, an epithelial Schwann S cell line. We have
      previously shown that SH-SY5Y neuroblastoma cells produce insulin-like growth
      factor II (IGF-II), which acts by an autocrine mechanism to stimulate cell
      growth. In the current study, we examined the effect of IGF-II on SH-EP
      neuroblastoma cells. Northern blot and reverse transcriptase-polymerase chain
      reaction analyses indicate that SH-EP cells do not produce IGF-I or IGF-II but
      express the type I and type II IGF receptors (IGF-IR and IGF-IIR). Cell surface
      expression of IGF-IR, assessed by fluorescence-activated sorting, was lower in SH
      EP cells than in SH-SY5Y cells. Immunoprecipitation of IGF-IR, followed by anti
      phosphotyrosine or anti-IGF-IR immunoblotting, demonstrated functional expression
      of these receptors in both cell types and confirmed the lower level of IGF-IR
      expression in SH-EP cells. IGF-II promoted SH-EP cell growth in the presence of
      low concentrations of calf serum (0.1-0.3%) or 10 ng/ml epidermal growth factor
      (EGF). IGF-II stimulation of SH-EP growth was eliminated by the IGF-IR blocking
      antibody (alpha IR-3) but not by an IGF-IIR blocking antibody. Stimulation of
      cell growth via this receptor was also indicated by the ligand specificity for
      IGF analogs and insulin (IGF-II approximately IGF-I approximately des(1-3)IGF-I
      >> insulin). These results indicate that in the presence of a permissive factor
      such as calf serum or EGF, IGF-II stimulates SH-EP cell growth via the IGF-IR.
      Collectively, these data suggest that within primary neuroblastomas, IGF-II may
      act as a paracrine factor to contribute to the promotion of S cell growth.

PMID- 7589245
TI  - Sizing highly fragmented DNA in individual apoptotic cells using the comet assay
      and a DNA crosslinking agent.
AB  - TK6 human B lymphoblast cells exposed to ionizing radiation undergo apoptosis in
      a time and dose-dependent manner. The resulting highly fragmented DNA is easily
      detected using the comet assay, a sensitive microscopic gel electrophoresis
      method capable of measuring DNA strand breaks in individual cells. The degree of
      DNA fragmentation may be indicative of different stages in the fragmentation
      process, responses to different agents, and/or cell type-dependent differences.
      In an effort to determine the number of breaks present in each apoptotic cell, we
      first applied a DNA-crosslinking agent, mechlorethamine, to TK6 cells containing
      a known number of DNA double-strand breaks produced by X rays. As the
      concentration of mechlorethamine increased, crosslinked DNA was less able to
      migrate during gel electrophoresis. Exposure of TK6 cells to 5 microM
      mechlorethamine prior to irradiation with 20 Gy was sufficient to "hide" the
      presence of these breaks by preventing DNA from migrating during electrophoresis.
      However, in apoptotic TK6 cells, it was necessary to apply a dose of
      mechlorethamine several times higher in order to produce a similar degree of
      inhibition of DNA migration. Calibrations using either the alkaline or neutral
      comet assays indicate that the average DNA fragment size in apoptotic TK6 cells
      is about 50 kb. Even in cells containing only 10-20% of the original amount of
      DNA, the remaining fragments still averaged about 50 kb, indicating that
      fragmentation to much smaller sizes occurs in some parts of the genome before
      others. When Chinese hamster V79 cells were exposed to hyperthermia (45 degrees C
      for 20 min), necrosis was induced over a period of several days. The size of DNA
      fragments in these cells was considerably larger (200-400 kb) and heterogeneity
      in appearance of comets was larger than observed for TK6 cells. This crosslinking
      method may be useful in discriminating cells dying by apoptosis from cells
      damaged or dying by other mechanisms.

PMID- 7589247
TI  - Ricin toxicity and intracellular routing in tumoral HT-29 cells. I. Ricin routing
      and toxicity are related to the state of differentiation of HT-29 cells.
AB  - We previously showed that ricin, which is more cytotoxic to undifferentiated than
      to differentiated tumoral HT-29 cells, enters these cells by different routes.
      The final steps of ricin endocytosis were investigated in order to identify the
      translocation site from which ricin exerts its toxicity. Toxicity measurements
      and kinetic experiments followed by subcellular fractionation were run in
      parallel. In differentiated cells, from 20 min of internalization, radiolabeled
      ricin was found in a Golgi-enriched fraction. At 60 min, which corresponds to the
      lag time for ricin toxicity, the amount of radioactivity located in this fraction
      decreased without any concomitant increase in the other fractions. In
      undifferentiated cells, from 20 min of incubation, radiolabeled ricin was
      detected in the ER-enriched fractions. At 30 min, the lag time for ricin
      toxicity, the amount of radioactivity detected in these fractions decreased
      without any concomitant increase in the Golgi-enriched fraction. Monensin, which
      was used to confirm the passage of ricin through the Golgi, greatly increased
      ricin toxicity and diminished the lag time only in differentiated cells.
      Brefeldin A inhibited ricin toxicity when added before the end of the lag time in
      both cell populations and reduced the amount of ricin detected, respectively, in
      the Golgi- and ER-enriched fractions in differentiated and undifferentiated
      cells. We propose that ricin enters the cytosol from the Golgi apparatus and
      essentially from the ER in differentiated and undifferentiated HT-29 cells,
      respectively, and that these different intracellular routings might explain the
      differential toxicity of ricin.

PMID- 7589248
TI  - Ricin toxicity and intracellular routing in tumoral HT-29 cells. II. Differential
      ricin toxicity from the apical and basolateral surfaces of differentiated HT-29
      cells.
AB  - We previously showed that ricin, a toxin commonly used in the construction of
      immunotoxins, was more toxic to undifferentiated than to differentiated HT-29
      tumoral cells. This results from differences in the intracellular routings of the
      toxin. As these studies concerned the entry through the apical pole of
      differentiated polarized HT-29 cells, we investigated and compared the
      intracellular routing of ricin from the apical and basolateral membranes of
      differentiated HT-29 cells and the toxicity of ricin depending on the pole of
      administration. For this purpose, we developed the culture of polarized HT-29
      cells on porous membrane filters and demonstrated that differentiated HT-29 cells
      can establish a leakproof monolayer. Ricin is 2.5-fold less toxic when it is
      added at the basolateral than at the apical pole of the cells, which may result
      from different observations: (1) less ricin is bound at the basolateral membrane
      than at the apical one, leading to a lesser internalization of the toxin; (2)
      ricin sorting in the apical and basolateral endocytic compartments of HT-29 cells
      differs: apically internalized ricin is targeted intracellularly while
      basolaterally internalized ricin uses mainly the transcytotic pathway; using
      NH4Cl and monensin, we observed that ricin follows the same pathway from both
      sides of the cells, namely the endosomal system, to reach the Golgi apparatus
      from which toxin intoxication occurs; (3) kinetics studies showed that a delay
      exists before an efficient intoxication by the basolateral pole is observed. The
      use of monensin at low concentration in order to perturb only the Golgi functions
      indicated that this delay could account for a different presentation of the toxin
      toward the membrane of the apical and basolateral endocytic compartments.
      Together, our results showed that, in differentiated HT-29 cells, if the pathways
      carrying ricin from the apical and basolateral membranes to the Golgi apparatus
      appear identical, ricin exerts differentially its toxicity depending upon the
      surface of administration, i.e., the apical or the basolateral surface of the
      cells.

PMID- 7589246
TI  - Translocation of cortactin (p80/85) to the actin-based cytoskeleton during
      thrombin receptor-mediated platelet activation.
AB  - Cortactin (p80/85) was discovered as a src kinase substrate and an actin filament
      binding protein. We investigated translocation of cortactin to the cytoskeleton
      during thrombin receptor-mediated platelet activation. Only a few percent of
      total cortactin (minor cortactin pool) translocates to the cytoskeleton as early
      as 5 s after platelet activation, while about 40% of total cortactin (major
      cortactin pool) is thereafter recovered in the cytoskeleton during platelet
      aggregation. Pretreatment of platelets with cytochalasin D suppresses completely
      this translocation, indicating that the translocation is dependent on actin
      polymerization. Inhibition of platelet aggregation by a tetrapeptide with the
      sequence RGDS, chelator of extracellular Ca2+, or a nonstirring condition results
      in marked suppression of translocation of the major cortactin pool. These results
      suggest that a minor cortactin pool translocates to the cytoskeleton independent
      of GPII-bIIIa (alpha IIb beta 3 integrin) engagement, and a major pool requires
      GPIIbIIIa-mediated signals into the cell for the translocation. Methyl 2,5
      hydroxycinamate, a tyrosine kinase inhibitor, inhibits tyrosine phosphorylation
      of cortactin without affecting its translocation, indicating that tyrosine
      phosphorylation is not essential for the translocation. Morphological studies
      reveal that cortactin is colocalized with filamentous actin in aggregated
      platelets and that it is localized at the cell peripheries along actin filaments
      in spread platelets. Taking these together, we have demonstrated in this paper
      that the translocation of cortactin is associated with the reorganization of the
      actin-based cytoskeleton during platelet activation, particularly with platelet
      aggregation.

PMID- 7589249
TI  - Characterization and localized expression of the laminin binding protein/p40
      (LBP/p40) gene during sea urchin development.
AB  - We have isolated and characterized the expression of a cDNA clone from the sea
      urchin Strongylocentrotus purpuratus that encodes a protein very similar to
      LBP/p40, originally identified as a nonintegrin, 67-kDa laminin binding protein.
      The deduced amino acid sequence of the protein, which we call spLBP/p40, shows
      significant similarity with the LBP/p40 from other sources, although significant
      divergence does occur at the carboxyl end. The S. purpuratus mRNA is present as a
      maternal transcript and its level remains constant until activation of zygotic
      transcription at the hatching blastula stage, whereupon the total spLBP/p40
      increases through the pluteus larval stage. Adult tissues also contain the
      spLBP/p40 mRNA. Both maternal and zygotic transcripts are translated as
      determined by their presence in polysomes. Immunoblot analysis using an antibody
      raised against a recombinant fusion protein indicates that the concentration of
      the spLBP/p40 protein remains constant during development despite the
      postblastula increase in mRNA concentration. However, the spatial distribution of
      the protein changes from a uniform, intracellular distribution in all cells of
      cleavage and blastula stages to localized, elevated levels in cells of the gut,
      primary mesenchyme, and oral epithelium of prism larvae. The distribution of
      spLBP/p40 mRNA at different developmental stages, analyzed by in situ
      hybridization, reflects that of the protein. Our results argue against a laminin
      binding function for this protein; instead they place the spLBP/p40 gene in a
      class of previously described sea urchin genes involved in growth and
      proliferation.

PMID- 7589250
TI  - Participation of the NG2 proteoglycan in rat aortic smooth muscle cell responses
      to platelet-derived growth factor.
AB  - Through immunohistochemical studies we have identified the cell-surface
      proteoglycan, NG2, on blood vessels throughout the rat embryo. The particular
      cell type expressing this chondroitin sulfate proteoglycan, however, is dependent
      upon tissue location. Microvessels within the rat CNS express NG2 on endothelial
      cells, while in blood vessels outside the CNS, NG2 is found on smooth muscle
      cells. To analyze what role NG2 might play in these blood vessels, an enzymatic
      dissociation protocol was used to establish primary cultures of vascular smooth
      muscle cells from Postnatal Day 3 rat aorta. In this study we demonstrate the
      involvement of NG2 in the mitogenic and chemoattractant responses of smooth
      muscle cells to PDGF. In assays measuring either DNA synthesis or cell migration,
      treatment of smooth muscle cells with anti-NG2 immunoglobulins decreased their
      responses to PDGF-AA but had no effect upon their ability to react to PDGF-BB.
      These results support a role for NG2 in potentiating signaling through the alpha
      PDGF receptor in vascular smooth muscle cells. The presence of the proteoglycan
      on a large subpopulation of these cells could provide an enhanced response to the
      growth factor in times of active normal growth or in pathological conditions,
      such as arterial injury or atherosclerosis.

PMID- 7589252
TI  - Cell-cycle-regulated localization of tyrosine and threonine phosphoepitopes at
      the kinetochores of mitotic chromosomes.
AB  - We have detected novel phosphotyrosine epitopes at the kinetochores of mitotic
      chromosomes in rat kangaroo PtK1 and mouse P388D1 tissue culture cells.
      Immunofluorescence labeling of detergent-resistant cytoskeletons reveals that
      these phosphotyrosine epitopes are tightly bound at the centrosomes and
      kinetochores of mitotic cells. These phosphoepitopes are found at the
      kinetochores during only prophase and prometaphase. Inclusion of a mixture of
      phosphatase inhibitors in the cell extraction procedure was necessary to preserve
      these previously undetected phosphotyrosine epitopes. The use of the phosphatase
      inhibitor mixture also improved the detection of the centrosome and kinetochore
      antigens recognized by the monoclonal antibody MPM-2. The MPM-2 antibody labels a
      subset of phosphothreonine-containing antigens found primarily during M phase.
      Ultrastructural immunolabeling studies indicated that both the phosphotyrosine
      and the MPM-2 phosphoepitopes were contained in both the outer and the inner
      dense plaques of the kinetochore. We developed large-scale chromosome isolation
      procedures designed to maintain chromosome protein phosphorylation. Immunoblot
      analysis revealed that the phosphotyrosine and MPM-2 antibodies recognized a
      number of chromosomal proteins, some of which were concentrated in the chromosome
      scaffold fraction prepared by nuclease digestion and salt extraction of whole
      chromosomes. The strictly regulated appearance of the phosphotyrosine and MPM-2
      epitopes at the kinetochores of chromosomes during various stages of mitosis
      suggests that these phosphoepitopes may be involved in signal transduction
      pathways controlling kinetochore assembly and function during mitosis.

PMID- 7589251
TI  - Enhanced expression of myogenic regulatory genes in aging skeletal muscle.
AB  - MyoD, myogenin, myf-5, and MRF4, belonging to the family of basic helix-loop
      helix (bHLH) myogenic regulatory factors (MRFs), control muscle cell
      differentiation, in concert with other transcription factors such as MEF-2, yet
      their role in age-related skeletal muscle alteration has not been addressed. We
      here report that MyoD and myogenin transcripts are expressed at high levels in
      the hind limb muscles of newborn mice and their level of expression continuously
      declines throughout postnatal life to become virtually undetectable in the adult
      mouse. However, these transcripts are again expressed at high levels in the
      muscles of older mice. MRF4 transcript, on the other hand, is present at a
      constant level throughout the life span of the animal. Conversely, the
      expressions of myf-5 and MEF-2C, components of the autoregulatory loop for the
      activation of bHLH gene expression, conspicuously increase in adult and senile
      muscle. In order to establish whether these transcripts are functioning in the
      aged muscle we investigated the expression of bHLH inhibitory factor Id mRNA
      showing that it does not present significant changes during aging.
      Immunofluorescence analysis with an anti-myogenin antibody revealed nuclear
      accumulation of the protein in the muscle fibers of old, but not of adult, mice.
      Muscle-specific genes transactivated by MyoD and myogenin such as AChR, MLC, and
      MCK are also up-regulated during aging, albeit at a lower level. Significant
      changes in the size and ratio of type I/type II fibers are detectable in senile
      muscle. These findings show that all members of the MRF family are expressed to a
      high extent and are likely active in senile muscle. It is conceivable that these
      changes might operate as a compensatory mechanism in maintaining the expression
      of differentiated muscle products in senile muscle at a steady-state level.

PMID- 7589253
TI  - Behavior of nuclear matrix proteins during camptothecin-induced apoptosis in HL
      60 human leukemia cells.
AB  - In this study we focused our attention on the behavior of four nuclear matrix
      proteins during the various stages of apoptosis in the HL-60 cell line exposed to
      the DNA topoisomerase I inhibitor, camptothecin. We have examined the following
      antigens by immunocytochemical techniques: (i) the 180-kDa nucleolar isoform of
      DNA topoisomerase II; (ii) a 126-kDa polypeptide of nuclear bodies; (iii) a 125
      kDa protein; and (iv) a 160-kDa polypeptide which are known to be components of
      the matrix inner network. Indirect immunofluorescence experiments were performed
      to follow these nuclear matrix antigens during apoptosis. Moreover, the
      ultrastructural localization of both 125- and 160-kDa proteins was investigated
      by electron microscope immunocytochemistry with gold-conjugated secondary
      antibodies. While the antibody to the nucleolar isoform of DNA topoisomerase II
      gave a fluorescent pattern that was well-maintained until the late phases of
      apoptosis, the other three nuclear antigens showed marked modifications in their
      distribution. A common feature, particularly evident for 125- and 160-kDa
      proteins, was their absence from cap-shaped chromatin marginations, whereas they
      were present in the areas of remaining decondensed chromatin. The 126-kDa
      polypeptide concentrated progressively in an irregular mass at the opposite side
      of the crescentic caps and then broke up in fine spots. The 125- and 160-kDa
      proteins localized in the nucleolus and precisely within certain granules which
      are known to appear in the nucleolar area after camptothecin administration.
      These results show that, in addition to the well-known chromatin changes, nuclear
      organization undergoes other rearrangements during the apoptotic process.

PMID- 7589256
TI  - Ligand-induced recruitment and phosphorylation of reduced TGF-beta type I
      receptor.
AB  - Receptors I (T beta R-I) and II (T beta R-II) of transforming growth factor-beta
      (TGF-beta) are components of a heteromeric complex in which receptor I requires
      receptor II to bind ligand, and receptor II requires receptor I to signal. We
      show that pretreatment of cells with low concentrations of dithiothreitol, which
      is known to disrupt ligand binding to T beta R-I, does not prevent interaction
      and complex formation between T beta R-II and T beta R-I. Nevertheless, our
      results demonstrate that ligand interaction with T beta R-I is able to induce
      high-affinity convertion to the complex formed. We also demonstrate that
      transphosphorylation of T beta R-I through bound T beta R-II can occur
      independently of ligand binding to T beta R-I.

PMID- 7589254
TI  - The immunolocalization of nuclear antigens during the pollen developmental
      program and the induction of pollen embryogenesis.
AB  - The immunolocalization of nuclear antigens, combined with cytochemical procedures
      as well as in situ hybridization and recent in situ molecular methods, has been
      applied at different steps of pollen development to characterize the functional
      organization of the nucleus during the formation of the male gametophyte in an
      agronomically interesting plant, Capsicum annuum L. Pollen embryogenesis has been
      induced in pepper and the first stages of the process have been studied at the
      cellular level. Low temperature processing methods including cryosections and
      Lowicryl sections were very convenient for performing the various in situ
      techniques used in the pollen grains. Different molecular probes for localizing
      DNA, RNA, snRNPs, specific nucleolar proteins, various rRNA species, and DNA/RNA
      hybrids provided positive results in the pollen nuclei. The data obtained, and
      the changes observed in the organization of the nuclear compartments during
      pollen development, are related to the variations in gene activity undergone by
      the male gametophyte. The methodology used is proposed as a very convenient
      approach to localize molecules and events involved in the nuclear function in
      both gametophytic and sporophytic pollen development.

PMID- 7589255
TI  - Induction of p53-independent apoptosis by hygromycin B: suppression by Bcl-2 and
      adenovirus E1B 19-kDa protein.
AB  - Hygromycin B, an aminoglycoside antibiotic that is widely used to establish
      stable mammalian cell lines that carry a bacterial gene conferring resistance to
      the drug, is shown here to induce apoptotic programmed cell death in susceptible
      cells. Dying cells exhibited typical features of apoptosis, including cell
      shrinkage, membrane blebbing, nuclear pyknosis, and extensive internucleosomal
      fragmentation of DNA. Employing concentrations of hygromycin B that are typically
      used for selecting stable cell lines, we show that susceptible cells die rapidly,
      exhibiting the morphological properties of apoptosis by 18 h and detectable DNA
      fragmentation as early as 2 h after receiving the drug. G418, on the other hand,
      required days to cause cell death, which was not accompanied by internucleosomal
      DNA fragmentation. Apoptotic cell killing by hygromycin B did not require
      expression of wild-type p53 and was suppressed by both Bcl-2 and the Adenovirus
      type 5 E1B 19-kDa protein.

PMID- 7589257
TI  - Delayed translation and posttranslational processing of cyritestin, an integral
      transmembrane protein of the mouse acrosome.
AB  - This paper presents data on the cellular localization of the testis-expressed
      mouse Cyrn gene product, cyritestin. This cysteine-rich protein is a member of a
      family including various rodent and primate proteins and snake venom proteins of
      the metalloproteinase and disintegrin types. By using antibodies raised against
      recombinant proteins generated in bacteria and against synthetic peptides we show
      that (i) Cyrn mRNA is present in germ cells 4 days prior to translation; (ii)
      cyritestin protein is localized in the acrosomal region of spermatids and
      spermatozoa; and (iii) cyritestin has an apparent molecular weight of 110,000
      Daltons, but is subject to processing during epididymal sperm transport,
      resulting in a shorter molecule lacking approximately 55 kDa from the N-terminal
      half. We conclude that cyritestin becomes exposed on the sperm surface after
      successful acrosome reaction and thus may play a role in sperm function rather
      than in testicular germ cell maturation.

PMID- 7589262
TI  - Salmonella outbreak from microwave cooked food.
AB  - Following a buffet meal served to six guests at a private domestic function, five
      of the guests and the host developed symptoms of food poisoning. Salmonella
      enteritidis phage type 4 (PT4) was isolated from all four individuals who
      submitted faecal samples for investigation. Leftover samples of a savoury rice
      dish consumed by all six ill persons contained 6 x 10(3)/gm Salmonella
      enteritidis PT4. The rice salad comprised boiled rice, raw carrots, eggs, cheese
      and curry powder. The curry powder and remainder of the pack of six eggs were
      negative on microbiological analysis. The rice dish had been prepared by heating
      in a 500 W microwave oven with a rotating turntable on full power for 5 min.
      Although the hazards of inadequate microwave cooking are well recognized, this is
      only the second outbreak of food poisoning from microwave cooking to be reported.

PMID- 7589258
TI  - Treatment of human fibroblasts with vanadate and platelet-derived growth factor
      in the presence of serum inhibits collagen matrix contraction.
AB  - Human fibroblasts cultured in an anchored collagen matrix reorganize the matrix
      and develop stress. Upon experimental release of the matrix, cells contract the
      matrix, a phenomenon that has been studied as an in vitro model of wound
      contraction. We have found that treatment of fibroblasts in stressed collagen
      matrices with vanadate and platelet-derived growth factor (PDGF) in serum
      containing medium inhibits the ability of cells to contract the matrix.
      Vanadate/PDGF/serum stimulation did not block contraction immediately, but rather
      resulted in generation of an inhibitory signal that developed over a period of 80
      min. The signal was highly specific since other factors such as lysophosphatidic
      acid and epidermal growth factor were unable to replace PDGF or serum. The
      presence of vanadate also blocked dephosphorylation of p-Tyr-PDGF receptors after
      PDGF/serum stimulation and caused accumulation of tyrosine-phosphorylated
      proteins in the cells. In parallel experiments, fibroblasts in monolayer culture
      were found to undergo reorganization of their actin cytoskeleton when treated
      with vanadate in the presence of PDGF and serum-containing medium. Our results
      suggest that a p-Tyr signaling pathway is important in the regulation of wound
      contraction.

PMID- 7589260
TI  - Inhibition of the melanoma cell cycle and regulation at the G1/S transition by 12
      O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity.
AB  - The growth of malignant melanoma cells is inhibited by 12-O-tetradecanoylphorbol
      13-acetate (TPA) while the growth of normal melanocytes is stimulated. We
      previously demonstrated that TPA inhibits the growth of Demel melanoma cells and
      leads to arrest at both at the G1/S and G2/M cell cycle transitions. To
      investigate the mechanism by which TPA arrests melanoma cell growth at the G1/S
      transition we have examined its effects on the levels of cyclins and cyclin
      dependent kinases (CDKs) and activation of CDK2 kinase activity. Addition of TPA
      in G1 blocked the increase in the level of p34cdc2 mRNA, but not of CDK2 mRNA.
      When TPA was added in G1, it inhibited the mobility shift of CDK2 reflecting a
      change in phosphorylation state. This corresponded to inhibition of the increase
      in CDK2 histone H1 kinase activity. There was little effect on the level of CDK4.
      Treatment with TPA during G1 caused a three to four fold increase in cyclin D1
      mRNA expression, but blocked the increase in the expression of cyclin A and
      cyclin B mRNAs later in the cell cycle. TPA caused a small increase in levels of
      cyclin D1 and had little effect on cyclin E, suggesting these G1 cyclins were not
      limiting. Addition of TPA in G1 prevented an increase in cyclin A levels,
      suggesting cyclin A might play an important role in mediating the growth
      inhibition. Examination of the levels of the CDK inhibitors p21Cip1 and p27Kip1
      showed that the level of these inhibitors was higher in G1 and dropped as cells
      entered S phase. In the presence of TPA this decrease did not occur. These
      results demonstrate that TPA blocks the G1/S transition in Demel melanoma cells
      in late G1 by mechanisms which regulate phosphorylation and activation of the
      CDK2 kinase. These mechanisms include preventing the decrease in p21Cip1 and
      p27Kip1 kinase inhibitors and limiting the amount of cyclin A.

PMID- 7589259
TI  - Degradation of fibronectin fibrils by matrilysin and characterization of the
      degradation products.
AB  - Matrilysin is a metalloproteinase expressed in a variety of tumors as well as in
      some types of normal tissue. In addition to regulating normal tissue remodelling,
      metalloproteinases are believed to play a role in tumor cell invasion and
      metastasis by degrading components of the extracellular matrix, for example the
      highly insoluble fibronectin fibrils found in the interstitial stroma. In this
      study we examined whether matrilysin can degrade fibronectin fibrils produced by
      human foreskin fibroblasts and characterized the degradation products of soluble
      fibronectin. Using indirect immunofluorescence microscopy, we demonstrate for the
      first time degradation of the fibronectin fibrils upon incubation with 15 nM
      active matrilysin. Removal of matrilysin resulted in regrowth of the fibrils,
      suggesting that matrilysin was not cytotoxic. Immunoblotting with specific
      monoclonal antibodies revealed initial degradation of soluble fibronectin within
      1 h. Further degradation occurred over a period of 20 h. Degradation of soluble
      fibronectin resulted in one fragment of 58 kDa containing the gelatin-binding
      domain, two fragments of 37 and 38 kDa, which were part of the cell attachment
      domain, and three fragments of 36, 33, and 30 kDa recognized by an antibody
      raised against the C-terminal heparin-binding domain. In addition to most of
      these fragments, several intermediates and unique fragments of 31 and 34 kDa
      could be found in the conditioned medium of human foreskin fibroblasts treated
      with matrilysin. Isolation of these fragments may allow further studies to
      determine their influences on cell migration, attachment, and signal
      transduction, which are expected to be different from the effects of undegraded
      fibronectin.

PMID- 7589261
TI  - Comparison of PFGE, ribotyping and phage-typing in the epidemiological analysis
      of Campylobacter jejuni serotype HS2 infections.
AB  - In this study we have evaluated the ability of three typing methods, pulsed field
      gel electrophoresis (PFGE), phage-typing and ribotyping, to discriminate not only
      between strains of differing serotypes but also between strains within a single
      serotype, heat stable serotype 2 (HS2). Forty-five isolates derived from cases of
      campylobacter enteritis occurring in the Cardiff area were examined. These
      included 18, mostly HS2, strains associated with an outbreak. The typing results
      for these and a further 39 epidemiologically unrelated strains of serotype HS2
      were compared. This is the first report documenting the use of PFGE in an
      epidemiological investigation of Campylobacter jejuni in the UK. The results
      presented suggest that this technique is the most discriminatory of the three
      subtyping methods examined.

PMID- 7589263
TI  - Clonal structure of invasive Streptococcus pyogenes in Northern Scotland.
AB  - We have used molecular techniques to characterize 51 group A streptococci from
      Scotland and 17 'serious disease' isolates from other countries, in order to
      establish the clonal structure of invasive Streptococcus pyogenes strains
      circulating between 1986 and 1993. Strains were grouped by restriction
      endonuclease analysis, pulsed field gel electrophoresis and ribotyping patterns,
      and were examined for the presence of alleles of the speA gene by polymerase
      chain reaction and DNA sequence analysis. Serious and fatal infections in
      Scotland were caused by several clones. One clone (9 of 51 strains) was M type 1
      and possessed the speA gene allele 2. This was the clone previously identified as
      causing severe infection in the USA. Another clone (5 of 51 strains) was M type 3
      and had speA gene allele 3. In view of the clear association of more than one
      clone with severe, invasive and fatal infections, horizontal gene exchange
      between genotypes merits further investigation.

PMID- 7589264
TI  - Beta-lactam resistance in normal faecal flora from South Africa.
AB  - The genetic and biochemical basis of ampicillin resistance amongst the aerobic
      Gram-negative commensal faecal flora of healthy volunteers in South Africa has
      been determined. Amongst 608 ampicillin resistant strains isolated from 320 of
      the participants, 158 were able to transfer their ampicillin resistant
      determinants into Escherichia coli K-12 J62-2. Iso-electric focusing of the beta
      lactamases, extracted from the transconjugants, demonstrated that ampicillin
      resistance resulted from the presence of the TEM-1, TEM-2 and SHV-1 beta
      lactamases in 94.3%, 2.5% and 3.2% of isolates respectively. Endonuclease
      restriction digests of the plasmids isolated from the transconjugants showed that
      the beta-lactamase genes were present on a wide variety of plasmid types; 101
      distinct plasmid endonuclease restriction patterns were identified. Transferable
      ampicillin resistance was associated with resistance to other antibiotics at the
      following frequencies: trimethoprim (48.7%), streptomycin (35.4%), tetracycline
      (27.2%), spectinomycin (9.5%), chloramphenicol (3.2%) and gentamicin (1.3%). One
      antibiotic resistance pattern, ampicillin and trimethoprim, predominated (28%).
      In total, 77.9% of the plasmids conferred resistance to other antibiotics raising
      the possibility that use of any of these agents, not simply ampicillin, may
      contribute to the maintenance of resistance genes.

PMID- 7589265
TI  - Prevalence and genetic location of non-transferable trimethoprim resistant
      dihydrofolate reductase genes in South African commensal faecal isolates.
AB  - In a recent survey of trimethoprim resistance, 357 Gram-negative aerobic
      organisms were isolated from healthy volunteers from rural and urban populations
      in South Africa. Trimethoprim resistance did not transfer to an Escherichia coli
      J62-2 recipient strain by conjugation in a liquid mating in 161 (45.1%) of the
      isolates. These isolates which did not transfer their resistance were probed with
      intragenic oligonucleotide probes for the types Ia, Ib, IIIa, V, VI, VII, VIII,
      IX, X and XII dihydrofolate reductase genes. Contrary to all previous data, the
      most prevalent dihydrofolate reductase gene in this group of non-transferable
      isolates which hybridized, was the type VII (38%) followed by the type Ia (25%),
      Ib (12%), V (1.7%) and VIII (1.2%). None of the strains hybridized to the types
      IIIa, VI, XI, X and the XII dihydrofolate reductase probes. Southern blots of
      plasmid and chromosomal DNA from selective isolates revealed that the type VII
      dihydrofolate reductase genes were located on the chromosome and were associated
      with the integrase gene of Tn21. However, the type Ib and V dihydrofolate
      reductase genes were all found on plasmids which could not be mobilized. The type
      Ia dihydrofolate reductase genes were found on both non-transferable plasmids and
      on the chromosome. The nature of the genetic structures associated with a
      dihydrofolate reductase gene strongly affects the means of spread of the gene in
      a population.

PMID- 7589266
TI  - PCR-based characterization of Yersinia enterocolitica: comparison with biotyping
      and serotyping.
AB  - PCR-based DNA fingerprinting was used to characterize 48 clinical isolates of
      Yersinia enterocolitica. The samples were examined by random amplified
      polymorphic DNA (RAPD-PCR) and inter-repeat PCR (IR-PCR). IR-PCR with two
      enterobacterial repetitive intergenic consensus primers resulted in patterns
      which were poorly discriminated; 2 of 11 arbitrary primers (RAPD-PCR) provided
      sufficient discriminatory power. In comparisons with serotyping and biotyping,
      RAPD-fingerprinting was the most discriminatory technique and may therefore be a
      valuable epidemiological tool for the study of Y. enterocolitica infections.

PMID- 7589267
TI  - An outbreak of cryptosporidiosis in south London: what value the p value?
AB  - An outbreak of cryptosporidiosis which affected 44 people in January and February
      1991 was identified through local surveillance at a South London Public Health
      Laboratory. Preliminary enquiries revealed that more than half the patients were
      adult and that there were no common factors other than geographical association.
      A case-control study showed a significant association between illness and
      consumption of tap water supplied by a particular water company, as well as a
      dose response effect. There were no apparent breaches or irregularities in the
      water distribution system and no indication of a problem through routine
      monitoring indices. This incident demonstrates the problems of establishing the
      source of cryptosporidiosis outbreaks in the absence of evidence of environmental
      abnormality, as well as possibly indicating that water conforming to current
      treatment standards may occasionally contain sufficient numbers of
      Cryptosporidium oocysts to cause sporadic cases or clusters.

PMID- 7589269
TI  - A serosurvey of water-borne pathogens amongst canoeists in South Africa.
AB  - Certain health risks have been associated with recreational exposure to faecally
      polluted water. Canoeing in certain South African waters is considered to be a
      high risk activity with regard to schistosomiasis, gastroenteritis and possibly
      hepatitis. In a cross-sectional study, a serosurvey was conducted amongst
      canoeists to ascertain whether or not they had a higher seroprevalence to
      hepatitis A virus, Norwalk virus and Schistosoma spp. than non-canoeists. In
      comparisons between the two groups, a significant association could not be
      demonstrated between canoeing and antibody response to hepatitis A and Norwalk
      viruses (P-values for age-adjusted chi 2 were 0.083 and 0.219 respectively), but
      a significant association could be demonstrated between canoeing and the antibody
      response to Schistosoma spp. (P < 0.001; age-adjusted).

PMID- 7589268
TI  - Poliomyelitis in The Netherlands: a review of population immunity and exposure
      between the epidemics in 1978 and 1992.
AB  - An overview of serological and virological studies on poliomyelitis in the
      Netherlands between two epidemics in 1978 and 1992 is given. Three unvaccinated
      patients acquired poliomyelitis abroad. In the Netherlands vaccination coverage
      with quadruple DPT-IPV vaccine is very high. The strong immunogenicity of
      inactivated poliovirus vaccine was confirmed in a cohort of children, reflected
      in age-stratified antibody profiles of the population. Adults born in the pre
      vaccination era appeared in general protected, but 10-25% of persons born between
      1930 and 1945 lacked neutralizing antibodies. Revaccination induced a booster
      type of antibody response in 75-90% of such persons, indicating immunological
      memory and protection. Virological studies on adopted children from other
      countries, patients with indications for viral examination, and river waters
      showed that the Netherlands was regularly exposed to polio virus (PV), without
      signs of indigenous transmission. Persons found to carry PV or their close
      contacts had travelled to a PV endemic country. Most of 557 isolates were vaccine
      derived, only 8% were wild type viruses. Despite their presence, up to 1992 the
      well-known susceptibles for PV in the Netherlands were shielded by the herd
      immunity of the Dutch population.

PMID- 7589270
TI  - Priorities in global measles control: report of an outbreak in N'Djamena, Chad.
AB  - In N'Djamena, capital of Chad, measles vaccination coverage of 12-23-month-old
      children fell from 61% in 1990 to 15% in 1993. A community survey of measles
      after an outbreak in 1993 showed that among children < 5 years of age, the mean
      monthly attack rate was 37 per 1,000 (95% CI, 32-43) and the mean case fatality
      rate was 7.4%. Measles incidence was highest (77/1,000/month) in children aged 9
      11 months and fell among children > 3 years of age. Incidence rates were high
      (56/1,000/month) among 6-8-month-old children, but only 3 deaths occurred in this
      age group. Measles vaccine efficacy, estimated by comparing attack rates in
      unvaccinated and vaccinated children, was 71% (95% CI, 59-80%). Extrapolation of
      the results to the city population indicated that an estimated 19,000 cases and >
      1,000 measles-associated deaths occurred in 1993. This preventable morbidity and
      mortality, in a city where coverage was formerly among the highest in Africa,
      shows the need for sustained global commitment to preventive health care.

PMID- 7589271
TI  - Measles vaccine efficacy during an outbreak in a highly vaccinated population:
      incremental increase in protection with age at vaccination up to 18 months.
AB  - During a large measles outbreak in Quebec City in 1989, two investigations
      conducted in parallel evaluated the relative risk of measles and measles vaccine
      effectiveness with respect to age at vaccination. The study was a school-based
      case-control study including 563 cases and 1126 classmate controls. The second
      was a cohort study of the siblings of school cases including 493 siblings aged
      between 1 and 19 years. The relative risks (RR) of measles were similar in both
      settings and the trend towards increased vaccine efficacy with increasing age at
      vaccination was highly significant (P < 0.001). Vaccine efficacy rose from 85% in
      children vaccinated at 12 months of age to > or = 94% in those vaccinated at 15
      months and older. Even for children vaccinated at or after 18 months of age, the
      RR of measles was reduced when compared with children vaccinated between 15 and
      17 months of age (RR 0.61, CI 95% 0.33-1.15). Small changes in the timing of
      initial measles vaccination can have a major impact on vaccine efficacy.

PMID- 7589276
TI  - Which are the hematopoietic stem cells? [or: don't debunk the history!].

PMID- 7589272
TI  - The development of an age structured model for schistosomiasis transmission
      dynamics and control and its validation for Schistosoma mansoni.
AB  - Mathematical models are potentially useful tools to aid in the design of control
      programmes for parasitic diseases. In this paper, a fully age structured
      epidemiological model of human schistosomiasis is developed and parameterized,
      and used to predict trends in infection prevalence, intensity and prevalence of
      heavy infections over age and time during several rounds of mass and age targeted
      treatment. The model is validated against data from a Schistosoma mansoni control
      programme in Kenya.

PMID- 7589277
TI  - Hematopoietic reserve provided by spleen colony-forming units (CFU-S).
AB  - Using quantitative data available from the literature on murine hematopoiesis,
      the functional reserve of multipotential stem cells was calculated by comparing
      daily blood cell production with the potential of clonogenic spleen colony
      forming cells (CFU-S) to generate blood cells. The potential of the day-8 CFU-S
      (CFU-S-8) population is estimated to be from 4000 to 37,000 times greater than
      needed in steady-state hematopoiesis. The CFU-S population may thus serve to
      provide a functional reserve to supply large numbers of peripheral blood cells
      via committed lineage-specific cells within days, whenever needed.

PMID- 7589274
TI  - Roe deer as sentinels for endemicity of tick-borne encephalitis virus.
AB  - The suitability of serological surveys of roe deer (Capreolus capreolus) in
      determining the spread of tick-borne encephalitis virus (TBEV) was tested in a
      south German area with a low risk of TBEV infection to humans. Sera obtained from
      192 hunted roe were screened by an haemagglutination-inhibition test (HAI) and in
      an ELISA developed in our laboratory. Those found positive were tested in a
      neutralization test (NT). Fifty (26.0%) sera reacted positive by ELISA and 43
      (86.0%) of these were confirmed by HAI or NT. Forty-seven (24.5%) samples were
      positive by HAI, 44 (93.6%) of which were also positive in NT or ELISA. Only
      insignificant increase of the antibody prevalence with age (P = 0.17 for HAI
      antibodies) suggests that most infections occur at an early age in scattered
      natural foci. The antibody prevalence in females was lower than in males (OR =
      0.63; P = 0.02 for HAI antibodies). In determining the distribution of
      seropositive roe we increased the sample size to 235 sera. No antibodies were
      detected in 56 (23.8%) sera collected in the eastern third of the county. The
      areas of high antibody prevalence in roe match those in which humans have been
      infected. We conclude that serosurveys of roe deer are useful in marking out
      areas in which humans face the risk of infection, provided that an adequate
      number of sera, preferably from males, is available.

PMID- 7589275
TI  - The transmission of Jembrana disease, a lentivirus disease of Bos javanicus
      cattle.
AB  - Methods of transmission of Jembrana disease, an acute and severe disease of Bali
      cattle (Bos javanicus) caused by a recently-identified bovine lentivirus known as
      Jembrana disease virus, are described. During the acute disease virus can be
      detected in saliva and milk. There is evidence of direct transmission from
      acutely affected animals in close contact with susceptible cattle, possibly by
      virus in these secretions infecting cattle by the conjunctival, intranasal or
      oral routes, by which it was possible to infect cattle experimentally. During the
      acute disease the titre of infectious virus in blood is high, about 10(8) 50%
      cattle infectious units (ID50)/ml, and it is probable that the virus is also
      transmitted mechanically by haematophagous arthropods. Recovered cattle are also
      a potential but probably infrequent source of infection; recovered cattle are
      persistently viraemic but the titre of infectious virus in blood decreases to
      about 10(1) ID50/ml by 60 days after recovery from the acute disease, and virus
      cannot be detected in secretions.

PMID- 7589273
TI  - Laboratory reared Amblyomma hebraeum and Amblyomma variegatum ticks differ in
      their susceptibility to infection with Cowdria ruminantium.
AB  - The susceptibility of laboratory reared Zimbabwean Amblyomma hebraeum and A.
      variegatum ticks to infection with geographically distinct Cowdria ruminantium
      strains was investigated by feeding both species simultaneously on individual
      sheep infected with one of the four strains (Crystal Springs [Zimbabwe], Ball 3
      [South Africa], Gardel [Guadeloupe] and Nigeria [Nigeria]). A. hebraeum ticks
      demonstrated a high susceptibility to infection with all four C. ruminantium
      strains. In comparison, A. variegatum were less susceptible to infection with the
      Crystal Springs and Ball 3 strains (P < 0.001), but showed a similar
      susceptibility to the Gardel and Nigeria strains. The differences in
      susceptibility of A. variegatum to infection with the four strains of C.
      ruminantium correlated with the origin of these strains. The consistently higher
      susceptibility of A. hebraeum ticks to infection with geographically different C.
      ruminantium strains may be one explanation for the observation that heartwater is
      a more serious problem where A. hebraeum is the vector of the disease.

PMID- 7589278
TI  - The effects of interleukin-1 beta and tumor necrosis factor-alpha on in vitro
      colony formation by human hematopoietic progenitor cells exposed to doxorubicin
      or hydroquinone.
AB  - Previous studies have shown that treatment of bone marrow (BM) cells with
      interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) can
      protect hematopoietic progenitor cells (HPC) from the toxic effects of 4
      hydroperoxycyclophosphamide (4HC) or gamma-irradiation. Since doxorubicin (DX)
      and hydroquinone (HQ) may inhibit hematopoiesis through mechanisms similar to 4HC
      and gamma-irradiation, it was of interest to determine whether IL-1 beta or TNF
      alpha could protect HPC from DX and HQ as well. Bone marrow mononuclear cells
      (BMMNC) or purified HPC (pHPC) were exposed to 50 ng/mL IL-1 beta or 25 ng/mL TNF
      alpha alone or in combination with DX or HQ for 22 hours at physiological O2
      partial pressure and temperature. The cells were washed free of the cytokines and
      toxicants and plated in cytokine-containing semisolid medium. Under these
      concurrent cytokine +/- toxicant treatment conditions, neither IL-1 beta nor TNF
      alpha significantly affected progenitor cell frequencies (assessed as CFU-C) or
      lineage commitment compared with the medium-treated controls. Treatment with
      either 100 nM DX or 30 microM HQ, however, reduced CFU-C frequencies by
      approximately 70%. When BMMNC were used, treatment with neither IL-1 beta nor TNF
      alpha consistently protected CFU-C from either DX or HQ. In contrast, using pHPC,
      IL-1 beta or TNF-alpha treatment conferred nearly two-fold protection of CFU-C
      from DX in all donors tested. TNF-alpha protected CFU-C from HQ using pHPC from
      all but one donor, while IL-1 beta did not protect CFU-C from HQ. Using phPC,
      maximum protection of CFU-C from DX was reached at IL-1 beta or TNF-alpha
      concentrations above 10 ng/mL or 1 ng/mL, respectively. Treatment of pHPC with
      TNF-alpha for at least 8 hours was necessary before significant protection from
      DX could be detected. Therefore, we conclude that IL-1 beta and TNF-alpha can act
      directly on human HPC to protect them from the inhibitory effects of DX and that,
      to a lesser extent, TNF-alpha can directly protect HPC from HQ.

PMID- 7589279
TI  - The influence of serum tumor necrosis factor-alpha and interleukin-6
      concentrations on nonhematologic toxicity and hematologic recovery in patients
      with acute myelogenous leukemia.
AB  - To confirm the reported correlation of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) serum concentrations with nonhematologic toxicity after
      cytotoxic chemotherapy and to examine their possible effects on hematopoiesis, we
      evaluated serum TNF-alpha and IL-6 concentrations every 3 days during 21
      chemotherapy cycles in 11 patients with acute myelogenous leukemia (AML) and one
      patient with chronic myelogenous leukemia in blast crisis (CML-BC). All patients
      developed grade IV hematologic toxicity. In 13 patient cycles, grade III-IV
      nonhematologic toxicity developed: hepatic (nine), pulmonary (six), and
      stomatitis (five). In these patient cycles, IL-6 concentrations increased from
      10.1 pg/mL (4.6-15.6, 95% CI) before nonhematologic toxicity to 64.8 (5.3-124.2,
      95% CI) at the onset of toxicity (p = 0.02). TNF-alpha concentrations were not
      detectable before nonhematologic toxicity but increased to 20.4 pg/mL (not
      detectable [ND]-45.5, 95% CI) at the onset of grade III-IV toxicity. In six
      patient cycles, grade II nonhematologic toxicity developed: hepatic (five),
      pulmonary (one), and stomatitis (two). In these six, IL-6 concentrations
      increased from 12.1 pg/mL (6.8-17.4, 95% CI) before toxicity to 21.4 (11-31.8,
      95% CI) at the onset of toxicity (p = 0.03). TNF-alpha concentrations were
      detectable in one patient cycle before toxicity and detectable in only two
      patient cycles at the onset of toxicity. The peak IL-6 and TNF-alpha
      concentrations did not correlate with the onset of nonhematologic toxicity in 87%
      of patient cycles. In patient cycles with a cumulative IL-6 area-under-the-serum
      concentration vs. time curve (AUC) > 1000 pg/mL.d, platelet recovery (> 30 x
      10(9)/L and platelet transfusion-independent) occurred earlier at 21.9 days (18.7
      25.1, 95% CI) compared to the 30.6 days (23.6-37.5, 95% CI, p = 0.02) in patient
      cycles with an IL-6 AUC < 1000 pg/mL.d. Patient cycles with a cumulative TNF
      alpha AUC > 150 pg/mL.d required a mean of 17.5 units of red blood cells (RBCs)
      (9.3-25.7, 95% CI) compared to patient cycles with an AUC < 150 pg/mL.d, which
      required only 8.9 units of RBCs (6.2-11.7, 95% CI, p = 0.03). The peak
      concentration and AUC for IL-6 and TNF-alpha were not significantly different
      between those receiving growth factors (G-CSF, six; GM-CSF, one) and those not
      receiving growth factors (14). Endogenous IL-6 and TNF-alpha serum concentrations
      increase in patients who experience nonhematologic toxicity and correlate with
      hematologic recovery after chemotherapy.

PMID- 7589281
TI  - Ex vivo expansion of megakaryocyte precursors by preincubation of marrow
      allografts with interleukin-3 and granulocyte-macrophage colony-stimulating
      factor in vitro.
AB  - Protracted thrombocytopenia and bleeding remain serious complications in bone
      marrow transplantation (BMT). Major progress has been made in facilitating
      myeloid and erythroid engraftment, but little has been made in accelerating
      thrombopoiesis post-BMT. We report that in vitro preincubation of T cell-depleted
      BM allografts with a combination of interleukin-3 (IL-3) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) (0.1 microgram/mL each) (n = 8),
      for 3 days prior to infusion, expands megakaryocyte (MK) precursors. MK
      progenitor proliferation was assessed in plasma clot colony assays and liquid
      cultures following pre-exposure to IL-3/GM-CSF. We observed a 2.8-fold increase
      in the number of colony-forming units-megakaryocyte (CFU-MK) (17.3 +/- 5.2 vs.
      6.1 +/- 3.4) (p = 0.001) and a two-fold increase in burst-forming units
      megakaryocyte (BFU-MK) (0.2 vs. 0.1) (p = 0.01) per 2 x 10(5) cells/mL compared
      to control BM samples cultured for 3 days in medium alone. In secondary cultures,
      the continued presence of IL-3 and GM-CSF increased the number of CFU-MK by 200
      fold (p < 0.0001) over controls and by 9.7-fold over fresh BM. A 33-fold increase
      (p < 0.0001) in the number of BFU-MK was elicited compared to controls. In
      addition, IL-3 plus GM-CSF supported increased cellularity within the colonies.
      The presence of IL-3 or GM-CSF alone resulted in fewer MK colonies and fewer
      cells per colony than both cytokines combined. In liquid cultures, the percentage
      of cells expressing platelet glycoprotein (GP) IIb/IIIa in the continued presence
      of IL-3 and GM-CSF increased following preincubation, yielding a total of 16.0 +/
      2.3 x 10(4) MK/2 x 10(6) cells at day 10 of culture. We propose that ex vivo
      preincubation with IL-3 and GM-CSF can expand the number of MK precursors and may
      facilitate platelet recovery post-BMT.

PMID- 7589282
TI  - Growth factor consumption and production in perfusion cultures of human bone
      marrow correlate with specific cell production.
AB  - Perfusion cultures of human bone marrow mononuclear cells (BMMNC) provide a
      unique in vitro model of hematopoiesis, supporting growth of both accessory and
      hematopoietic elements. In this study, bioreactors were used to analyze the
      consumption and production of growth factors (GFs) in relation to each other and
      to the cells produced. The exogenously added GFs interleukin-3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor
      (SCF), and erythropoietin (Epo) each exhibited different, but reproducible,
      consumption kinetics. Epo and IL-3 were consumed slowly for the first 5-7 days,
      and then the consumption rate of both increased. Epo consumption reached a
      plateau by day 10, whereas IL-3 consumption continued to increase. Consumption of
      SCF was similar to that of Epo, but began 2-3 days earlier. GM-CSF was consumed
      throughout the culture period in an accelerating manner. Consumption of SCF and
      Epo were related, because omission of Epo from the growth medium reduced SCF
      consumption by 53% and omission of SCF reduced Epo consumption by 82%. A
      reproducible relationship between cumulative GF consumption and total cell
      production was observed. Epo was most potent, with 5900 molecules consumed per
      cell produced, whereas 69,400 molecules of SCF were consumed per cell generated.
      More specifically, Epo consumption was correlated (r = 0.92 and 0.96) with the
      number of glycophorin A-positive (glyA+) cells produced, and the rate of Epo
      consumption varied with the progression of cells through the erythroid lineage.
      Consequently, measurement of GF consumption rates may be useful for quantifying
      the types of cells present in a culture. Endogenous GF production was also
      examined. G-CSF and MIP-1 alpha were present at high levels during the first 4
      days but then declined rapidly. LIF first appeared in the second week and
      steadily increased thereafter. Omission of SCF from the medium allowed the
      detection of endogenous SCF production, and the kinetics was similar to that of
      LIF. IL-6 production was biphasic, with a peak and decline in week 1 and an
      increase during week 2. TGF-beta was below the level of detection in these
      cultures. The results suggest that perfusion supports accessory and hematopoietic
      elements which interact and therefore represent a partially functional tissue ex
      vivo. This system provides a useful model for studying relationships within GF
      networks and for elucidating the conditions that result in primitive cell
      expansion ex vivo.

PMID- 7589280
TI  - Adeno-associated virus 2-mediated gene transfer and functional expression of the
      human granulocyte-macrophage colony-stimulating factor.
AB  - It is becoming increasingly clear that the adeno-associated virus 2 (AAV)-based
      vector system may prove to be useful for high-efficiency gene transfer in human
      cells as well as for potential gene therapy in humans. A recombinant AAV vector
      containing the gene for a human hematopoietic growth factor, granulocyte
      macrophage colony-stimulating factor (GM-CSF), was constructed and used to infect
      COS-1 cells, a monkey kidney cell line. COS-1 cells infected with the recombinant
      virus, but not mock-infected cells, expressed high levels of the human GM-CSF
      gene transcripts. Furthermore, in co-cultivation experiments with the recombinant
      virus-infected cells, but not in those with mock-infected cells, active
      proliferation of a GM-CSF-dependent human megakaryocytic leukemia cell line,
      M07e, could be obtained in the absence of exogenously added GM-CSF. The
      recombinant GM-CSF protein released into the supernatant was biologically active
      in progenitor cell assays carried out with primary human hematopoietic cells, and
      this activity was specifically abrogated by treatment of the supernatant with
      anti-GM-CSF antibodies. This recombinant virus may be potentially useful in the
      management and gene therapy of a variety of malignant disorders in the human
      hematopoietic system.

PMID- 7589283
TI  - Altered in vivo and in vitro behavior of butanol-modified bone marrow cells.
AB  - Cell-surface molecules, particularly glycoconjugates, appear to be involved in
      the in vivo homing of hematopoietic stem and progenitor cells and in their
      interactions with hematopoietic stromal cells. To study the role of cell-surface
      molecules of hematopoietic stem cells, the expression of some surface molecules
      was altered using n-butanol treatment. We examined the in vivo and in vitro
      colony-forming abilities, in vivo homing patterns, and cell-surface lectin
      receptor expression of butanol-treated bone marrow cells (BMC) from BDF1 mice.
      The butanol-treated/-modified BMC formed an increased number of significantly
      larger spleen colonies (CFU-S) in lethally irradiated (1050 rad) mice. The
      butanol-treated BM formed significantly larger in vitro granulocyte-macrophage
      progenitor cell colonies (CFU-C) and in vitro fibroblastic colonies (CFU-F),
      although the number of such colonies was not significantly altered. The homing
      pattern of butanol-treated BMC was studied by comparing the distribution in
      lethally irradiated mice of intravenously injected 51Cr-labeled butanol-treated
      BMC with that of untreated cells. The butanol treatment altered the in vivo
      homing pattern of these cells, with increased homing to liver, spleen, and bone
      marrow and decreased homing to thymus, lung, and mesenteric lymph nodes. Flow
      cytometric analyses of butanol-treated BMC showed an increased expression of
      receptors for the lectins concanavalin A (conA) and wheat germ agglutinin (WGA),
      indicating an increased expression of mannosyl and galactosyl residues, which are
      known sugar moieties in hematopoietic stem/progenitor cell homing. These results
      indicate that cell surface modifications can influence homing and growth of
      transplanted BMC and that butanol treatment is a useful tool for studying the
      mechanisms of hematopoietic stem/progenitor cell homing in vivo and for further
      characterizing the molecules involved in this process.

PMID- 7589285
TI  - Survival of spleen colony-forming units (CFU-S) of irradiated bone marrow cells
      in mice: evidence for the existence of a radioresistant subfraction.
AB  - Because of increasing evidence of heterogeneity in the hematopoietic stem cell
      compartments, the radiosensitivity of spleen colony-forming units (CFU-S) was
      reevaluated to ascertain whether the classical single exponential curve for a
      graded dose of radiation is applicable at higher doses of radiation, 400-600 cGy.
      Bone marrow cells (BMC) removed from mice immediately after death under
      anesthesia were irradiated in vitro. Great care was taken to exclude anoxic
      effects during irradiation and to avoid any possible effects in the recipient
      mice from injection of excessive numbers of BMC. By estimating the number of
      cells to be injected to produce numbers of colonies within the evaluation range
      of the assay, we obtained a radiation survival curve that appeared to have a
      multiphasic concave shape; the D0 value for the 400-600 cGy range was estimated
      to be about 275 cGy, whereas the D0 for the lower doses was 95 cGy, the same
      value as previously reported. The reason a single exponential survival curve was
      previously obtained after graded doses of radiation is discussed, and a
      comparison of those results with the present data from in vitro radiation is
      made. Lacking experimental evidence, we speculate that the major factor that
      determines the slope of the survival curve is the degree to which the stem cells
      are in their normal hematopoietic environment during the irradiation. The
      probable existence of a fraction surviving after an exposure to 600 cGy,
      estimated by the limiting dilution assay, was about 1 per 2 x 10(6) BMC. Such
      radio-insensitive CFU-S appear to be primitive CFU-S, which can contribute
      materially to the long-term survival of lethally irradiated bone marrow
      recipients.

PMID- 7589284
TI  - IL-11 in combination with SLF and G-CSF or GM-CSF significantly increases
      expansion of isolated CD34+ cell population from cord blood vs. adult bone
      marrow.
AB  - Hematopoietic progenitor cells in human umbilical cord blood have been shown to
      be effective sources for hematopoietic reconstitution following myeloablative
      therapy. Unfortunately, the use of cord blood (CB) is limited by the number of
      progenitor cells necessary to reconstitute the older child or adult. We studied
      the expansion of an isolated population of CD34+ cells from CB and adult bone
      marrow (ABM) after 1 to 3 weeks in culture when stimulated with lineage
      nonspecific (IL-11 and/or SLF) and lineage-specific (G-CSF or GM-CSF) cytokines.
      IL-11 and SLF alone or in combination did not enhance expansion of CB CD34+ stem
      cells. With combinations of IL-11, SLF, and G-CSF or GM-CSF, however, after 1, 2,
      or 3 weeks in culture, WBC expansion was significantly greater in CB vs. ABM (p <
      0.05). At all time points, expanded CB consistently demonstrated a significant
      increase in cell production and myeloid differentiation when compared to ABM. To
      assess the proliferative potential of the expanded cultures, cells were recovered
      from the expansion cultures, plated in methylcellulose, and evaluated for CFU-GM
      and CFU-Meg colony formation. After 2 weeks in culture, a significant increase in
      CFU-GM colony formation in CB vs. ABM was demonstrated with SLF (p < 0.001), IL
      11 plus SLF (p < 0.0005), and IL-11 plus SLF plus G-CSF (p < 0.004).
      Significantly greater CFU-Meg formation was also seen in CB vs. ABM cells plated
      after expansion with IL-11 plus SLF plus G-CSF (weeks 1 and 2) or IL-11 plus SLF
      plus GM-CSF (week 1) (p < 0.05). Finally, immunophenotyping was performed on CB
      cultures on days 0 and 14, and although a significant reduction of the percentage
      of progenitors (CD34+/38+/38-/DR+) was seen, their absolute numbers were
      maintained. (Data for ABM was not available). This study suggests that IL-11,
      when combined with SLF and more lineage-specific cytokines, can effectively
      maintain primitive multipotential progenitors and stimulate the differentiation
      of more committed precursors in CB compared to ABM.

PMID- 7589286
TI  - Establishment and characterization of a novel human immature megakaryoblastic
      leukemia cell line, M-MOK, dependent on fibroblasts for its viability.
AB  - A novel fibroblast-dependent human immature megakaryoblastic leukemia cell line
      (M-MOK) was established from the bone marrow of a girl with acute
      megakaryoblastic leukemia, and its growth was determined to be completely
      dependent on the presence of human embryonic lung-derived fibroblasts, HEL-O.
      Adhesive interaction between M-MOK and HEL-O was crucial for viability; once HEL
      O was removed from the culture, mortality was total within a few days. On HEL-O
      cells, M-MOK could be passaged for more than 2 years. With regard to surface
      marker profile, the established cells were positive for CD11a, CD13, CD18, CD33,
      CD34, CD41b, CD42b, CD54, and c-kit antigens, but negative for HLA class II
      antigen and glycophorin. Histochemically, the cells were negative for
      myeloperoxidase, nonspecific esterase, and naphthol ASD chloroacetate esterase
      staining. Electron-microscope examination revealed the cells to be negative for
      platelet peroxidase (PPO). After induction of differentiation by a phorbol ester,
      however, the cells were demonstrated to be positive for PPO with a morphological
      change to megakaryocytes. From these results, M-MOK was considered to represent
      an immature cell line of megakaryocyte lineage. Studies of the mechanisms
      sustaining the HEL-O-dependent continuous in vitro growth of M-MOK cells revealed
      the following results: (1) M-MOK could grow even when separated from HEL-O by a
      nucleopore membrane; (2) conditioned medium (CM) from HEL-O supported the growth
      of M-MOK for more than 1 month without feeder cells; (3) the growth of M-MOK on
      HEL-O or CM supplement was nearly entirely inhibited by anti-GM-CSF (1
      microgram/mL); (4) GM-CSF mRNA was detected in HEL-O cells; and (5) HEL-O was
      found to secrete GM-CSF into the culture medium. Taken together, the growth of M
      MOK might therefore be driven by a soluble factor, that is, GM-CSF secreted from
      HEL-O cells. The presence of HEL-O, however, inhibited anti-GM-CSF-induced M-MOK
      death. Co-culture of M-MOK and HEL-O cells thus offers a useful experimental
      model for analysis of interactions between hematopoietic stem cells and stromal
      cells.

PMID- 7589288
TI  - Enhancement of monocytopoiesis by granulocyte colony-stimulating factor: evidence
      for secondary cytokine effects in vivo.
AB  - Granulocyte colony-stimulating factor (G-CSF) is used with increasing frequency
      to reduce the neutropenic interval following dose-intensive chemotherapy. In
      mice, exogenous G-CSF reduces neutrophil recovery after 5-fluorouracil (5-FU)
      treatment from 14 to 8 days. G-CSF treatment also enhances recovery of blood
      monocytes; colony assays show increased numbers of macrophage and granulocyte
      macrophage progenitors (CFU-M and CFU-GM) in the marrow. This unexpected effect
      of G-CSF treatment is dependent on endogenous M-CSF; antiserum to murine M-CSF
      inhibits both peripheral monocyte and monocytic progenitor recovery without
      affecting neutrophil or CFU-GM recovery. Conversely, the effect of M-CSF
      depletion is seen only in G-CSF-stimulated recovery; monocyte levels in mice
      treated with antiserum to M-CSF after 5-FU are indistinguishable from mice given
      5-FU alone. No synergy between G-CSF and M-CSF can be demonstrated in vitro with
      either normal or 5-FU-treated marrow, indicating this G-CSF/M-CSF interaction
      must be indirect. These results reveal an unpredicted beneficial effect of G-CSF
      treatment on monocyte recovery and a role for endogenous M-CSF in rebound
      hematopoiesis.

PMID- 7589287
TI  - Interferon-alpha-induced apoptosis in human erythroid progenitors.
AB  - Recombinant human interferon-alpha (rIFN-alpha) inhibits erythropoiesis, in vivo
      and in vitro. In an attempt to clarify mechanisms related to this inhibition,
      effects of rIFN-alpha on highly purified human peripheral blood burst-forming
      units-erythroid (BFU-E) (20-60% purity) were compared with effects on erythroid
      progenitors in various stages of development. Day-1 and -7 cultured cells were
      equivalent to primitive BFU-E and colony-forming units-erythroid (CFU-E),
      respectively. Day-1 BFU-E supported by recombinant human erythropoietin (rEpo)
      and interleukin-3 (rIL-3) was inhibited by rIFN-alpha in a dose-dependent manner,
      and a significant inhibition occurred at 2000 U/mL rIFN-alpha. Limiting dilution
      analysis demonstrated that rIFN-alpha directly inhibits BFU-E rIFN-alpha
      inhibited the proliferative capacity or the colony expression of erythroid
      progenitors, with no relation to the stage of development, but inhibition of
      differentiation was not apparent. This evidence suggested that apoptosis of
      erythroid progenitors was induced by IFN-alpha. When day-7 cells were incubated
      with IFN-alpha in the presence of rEpo, there was an increased breakdown of total
      cellular DNA into DNA fragments of less than 5 kb; hence, the inhibitory effect
      of IFN-alpha on erythroid progenitors may mediate apoptosis.

PMID- 7589289
TI  - Encoding of jaw movements by central trigeminal neurons with cutaneous receptive
      fields.
AB  - Neurons with orofacial cutaneous receptive fields that responded to jaw movements
      were recorded in the trigeminal subnucleus interpolaris of the cat. Movement
      related neuronal activity was identified by imposing passive ramp and hold
      stretches of the jaw at four different rates. Thirty-nine neurons with hair (26),
      skin (9), or convergent (4) receptive fields were studied. Thalamic projection
      neurons were identified by antidromic stimulation of the ventroposteromedial
      nucleus of the thalamus. The receptive fields of movement-related hair units
      included multiple hairs located mainly around the angle of the jaw and chin. The
      receptive fields of movement-related skin units were smaller than those of hair
      units and they were located primarily around the angle of the mouth. The
      convergent units had more than one receptive field that usually included hair or
      skin. All of the hair units were activated both during opening and closing jaw
      movements. They typically responded with short bursts of action potentials. Four
      units with skin receptive fields exhibited similar responses. The five skin units
      that did not show bursting activity included two that were active during both
      opening and closing of the jaw, two that were active only during opening, and one
      that was tonically active during maintained open position. All of the convergent
      units showed biphasic responses, and three responded with bursts. The maximum
      discharge rate, the mean discharge rate (mean bursting rate for units with
      bursting responses), and the total number of spikes per movement were measured.
      Statistical analysis was performed on these variables to assess functional
      properties of each unit. The results were used to classify units as velocity,
      speed, direction, or transient motion detectors. Thirty-three percent of the
      neurons were trigeminothalamic neurons.

PMID- 7589290
TI  - Magnocellular and parvocellular divisions of pigeon nucleus isthmi differentially
      modulate visual responses in the tectum.
AB  - The electrophysiological responses of 162 tectal cells to computer-generated
      visual stimuli were extracellularly recorded from 24 homing pigeons before and
      after injecting either lidocaine or N-methyl-D-aspartate (NMDA) into the nucleus
      isthmi pars magnocellularis (Imc) or the nucleus isthmi pars parvocellularis
      (Ipc). Micro-injections of lidocaine into Imc resulted in a significant reduction
      of firing rate in 80% of tectal cells, whose excitatory receptive fields (ERFs)
      were localized within the ERF of the Imc cell where the lidocaine was injected.
      In contrast, when lidocaine was injected into Ipc under identical circumstances
      it had no effect on the visually driven activity of 68% of tectal cells. However,
      when the excitatory amino acid NMDA was injected into Ipc it produced a
      significant reduction in the visually driven firing of 75% of tectal neurons when
      their ERFs were within the isthmic ERF, while similar application of NMDA into
      Imc had no effect on the visually driven response of 94% of tectal neurons. When
      the ERFs of tectal cells were localized outside the ERF of the isthmic cell where
      the chemical was injected, Imc-injected lidocaine had no effect in 9 out of 10
      tectal cells, whereas Ipc-injected NMDA increased firing in 7 out of 17 tectal
      cells. Therefore, it is suggested that the Imc-tectal fibers participate in a
      positive feedback pathway and the Ipc-tectal fibers are involved in a negative
      feedback pathway.

PMID- 7589291
TI  - Development of acetylcholinesterase-positive thalamic and basal forebrain
      afferents to embryonic rat neocortex.
AB  - By combining anterograde and retrograde axonal tracing with AChE histochemistry,
      we demonstrate the sources of AChE-positive afferents to embryonic neocortex, the
      pathways they use, their time of arrival into cortex, and their initial invasion
      of the cortical plate. Acetylcholinesterase (AChE) is expressed by two
      populations of cortical afferents: AChE is permanently present in basal forebrain
      fibers and has been reported to be transiently localized in axons of the
      principal sensory thalamic nuclei over the first few postnatal weeks beginning at
      the middle of the first week. We first detect AChE-positive afferents
      histochemically in neocortex on embryonic day seventeen (E17) and determine that
      they arise from the principal sensory thalamic nuclei. AChE histochemistry labels
      the entire length of developing thalamocortical axons, including their growth
      cones and branches. These AChE-positive afferents enter the neocortex by the
      internal capsule and take an intracortical pathway centered on the subplate
      layer. As soon as these axons are detected, some have already begun to extend
      AChE-positive collateral branches superficially toward the cortical plate. By
      E19, a few collaterals have entered the deep part of the cortical plate and by
      E21 have densely invaded all but its most superficial undifferentiated part. AChE
      positive afferents from basal forebrain structures reach the neocortex by three
      routes: the external capsule, the internal capsule, and the cingulate bundle.
      Among basal forebrain components, only the substantia innominata and nucleus
      basalis of Meynert reach the cortex by the internal capsule. Afferents from these
      two sources reach neocortex on E18, but are a very minor component of the total
      population of AChE-positive afferents at this age. Afferents from other basal
      forebrain components do not reach neocortex until several days later. The spatial
      and temporal patterns of AChE expression in developing thalamocortical axons
      indicate that it is useful for delineating their innervation of the primary
      sensory areas of embryonic neocortex, and suggest that AChE may function in axon
      extension and cortical differentiation.

PMID- 7589292
TI  - Effects of eye position on auditory localization and neural representation of
      space in superior colliculus of cats.
AB  - The maps of visual and auditory space within the superior colliculus are in
      approximate register both with each other and with the underlying motor maps
      associated with orienting responses. The fact that eyes and ears can move
      independently poses a problem for the sensorimotor organization of these two
      modalities. By monitoring eye and pinna positions in alert, head-fixed cats, we
      showed that the accuracy of saccadic eye movements to auditory targets was little
      affected by eye eccentricity (range +/- 15 deg) at the onset of the sound. A
      possible neural basis for this behavioral compensation was suggested by
      recordings from superior colliculus neurons. The preferred sound directions of
      some neurons in the deep layers of this midbrain nucleus exhibited a shift with
      the direction of gaze, while in others the response throughout the auditory
      receptive field was either increased or decreased, suggesting that changes in eye
      position alter the gain of the auditory response.

PMID- 7589294
TI  - Connections between the pulvinar complex and cytochrome oxidase-defined
      compartments in visual area V2 of macaque monkey.
AB  - We examined the distribution of pulvinar afferents to visual area V2 of macaque
      monkey cerebral cortex in relation to the distribution of the metabolic enzyme
      cytochrome oxidase (CO). V2 contains three sets of stripelike subregions that are
      marked by differential staining for CO, and which have different corticocortical
      connections. The pulvinar provides the major subcortical input to V2, and this
      input is known to be patchy. We were interested to determine how the pattern of
      pulvinar afferents relates to the layout of the three stripelike compartments
      that characterize V2. We made large injections of WGA-HRP into the pulvinar
      (labelling both the inferior and lateral divisions) and mapped the resulting
      orthograde terminal and retrograde cell label within V2. We observed pulvinar
      terminal label mainly in lower layer 3 (at the layer 4 border), with light label
      in layer 1 as well; terminal label in layers 3-4 was distributed in discrete
      patches with faint bridges of light label between. Comparison with adjacent
      sections stained for CO or Cat-301 showed that pulvinar terminal zones aligned
      precisely with regions of increased CO staining, and targeted both "thick" (Cat
      301+) and "thin" CO-rich stripes, avoiding the pale stripes (which aligned with
      the faint bridges of terminal label). Retrogradely labelled cells were found in
      layers 5A and 6, but the bulk of the feedback to pulvinar arose from layer 6
      rather than layer 5 (unlike V1, where feedback to pulvinar arises primarily from
      layer 5B). These results show that the increased CO staining in certain
      subregions of V2 is closely correlated with the presence of thalamic terminals
      from the pulvinar. Although we cannot rule out the possibility that different
      sets of pulvinar neurons project to different CO compartments in V2, the presence
      of a prominent thalamic input shared by the "thick" and "thin" CO stripes (which
      receive different V1 afferents and make different feedforward projections to
      other visual cortical areas) could underlie the preferential intrinsic
      interconnections shown to exist between these V2 subregions and suggests another
      potential source of integration between the two cortical visual streams.

PMID- 7589295
TI  - Cerebellar cortex and eyeblink conditioning: bilateral regulation of conditioned
      responses.
AB  - We examined the role of the cerebellum in classical conditioning of the
      nictitating membrane response (NMR) of rabbits by comparing the effects of
      unilateral and bilateral cerebellar cortical lesions. Using extended preoperative
      conditioning to ensure high levels of learning, we confirmed that unilateral
      lesions of lobules HVI and ansiform lobe impaired conditioned responses (CRs)
      previously established to an auditory conditioned stimulus, but did not prevent
      some relearning with post-operative retraining. Bilateral lesions of HVI and
      ansiform lobe produced similar impairments of CRs, but also prevented subsequent
      relearning. Unilateral cortical lesions produced significant enhancement of
      unconditioned response (UR) amplitudes to periorbital electrical stimulation.
      Bilateral cortical lesions enhanced UR amplitudes to a lesser extent. Because
      there was no correlation between the degree of CR impairment and UR enhancement
      across the unilateral and bilateral lesion groups, the suggestion that the
      lesions impaired CRs due to general effects upon performance, rather than due to
      losses of learning, is not supported. Both sides of the cerebellar cortex
      contribute towards learning a unilaterally trained CR. This finding is important
      for the re-interpretation of unilateral, reversible inactivation studies that
      have found no involvement of the cerebellar deep nuclei in the acquisition of NMR
      conditioning. In addition, we found conditioning-dependent modifications of
      unconditioned responses that were particularly apparent at low intensities of
      periorbital electrical stimulation. This finding is important for the re
      interpretation of studies that have found apparent changes in the UR of
      conditioned subjects after cerebellar lesions.

PMID- 7589297
TI  - Influence of hyperglycemia and of hypercapnia on cellular calcium transients
      during reversible brain ischemia.
AB  - The object of the study was to find out how preischemic hyperglycemia (in
      normocapnic animals) or excessive hypercapnia (in normoglycemic animals) affect
      the calcium transient during ischemia, as this can be assessed by measurements of
      the extracellular calcium concentration ([Ca2+]e). To that extent, normocapnic
      normoglycemic control animals were compared with animals with induced
      hyperglycemia or hypercapnia, all being subjected to 10 min of forebrain
      ischemia, the [Ca2+]e and d.c. potential being measured with ion-sensitive glass
      microelectrodes. Hyperglycemia and hypercapnia delayed the loss of ion
      homeostasis following induction of ischemia. Furthermore, both hyperglycemia and
      hypercapnia reduced the delay of Ca2+ extrusion upon recirculation. As a result,
      both hyperglycemia and hypercapnia significantly reduced the ischemic calcium
      transient, as this was assessed by calculating the duration of maximal calcium
      load of cells. The results make it less likely that aggravation of brain damage
      by hyperglycemia or excessive hypercapnia is related to a further derangement of
      cell calcium homeostasis.

PMID- 7589293
TI  - Distribution of non-phosphorylated and phosphorylated neurofilament proteins in
      the spinal cord of an anuran amphibian during development and regeneration.
AB  - The changes in the neurofilament medium and high molecular weight subunits (NF150
      and NF200) in the developing and transected spinal cords of bullfrog tadpoles
      were studied. A monoclonal antibody recognizing the nonphosphorylated epitope of
      NF150, NF150D, stained the neuronal cell bodies and axons, whereas other
      antibodies against the phosphorylated NFs, NF150P or NF200P, labeled chiefly the
      axons. During development, the intensity of axonal staining by the anti-NF150D in
      the ventral fasciculi in younger tadpoles appeared stronger than older animals,
      but the reverse was seen for NF150P and NF200P. Complete signal transection of
      stage IV tadpoles resulted in degeneration and then regeneration of the cord
      tissue of both cut ends. Each stump lengthened by about 350 microns in the 4
      weeks after the lesion. In the proximal stumps, the levels of NF150P or NF200P in
      the ventral axons at 550-350 microns proximal to the transection site increased
      notably by about 24-73% of the control value 7-28 days post-transection; however,
      the content of NF150D was decreased. The densities of NF150D and NF150P protein
      spots on the Coomassie blue-stained two-dimensional gels of the normal and
      injured cords also displayed alterations similar to the immunocytochemical data.
      Intense labeling by the anti-NF150P or NF200P was present in the cell bodies of
      axotomized motor neurons in the ventral horn. The results suggest that central
      axonal regeneration may be accompanied by upregulated phosphorylated
      neurofilament proteins.

PMID- 7589296
TI  - Integration in trigeminal premotor interneurones in the cat. 3. Input
      characteristics and synaptic actions of neurones in subnucleus-gamma of the oral
      nucleus of the spinal trigeminal tract with a projection to the masseteric
      motoneurone subnucleus.
AB  - A population of last-order interneurones within the rostrodorsal part of the oral
      nucleus of the spinal trigeminal tract (NVspo-gamma) has been investigated in 21
      chloralose anaesthetised cats. The neurones were identified by their antidromic
      (AD) response to microstimulation (median current 9 microA, range 3-39 microA) of
      the ipsior the contralateral masseteric subnucleus of the trigeminal motor
      nucleus. Fifty-one of 113 interneurones tested were discharged from the
      ipsilateral and eight from the contralateral motor nucleus. The average
      conduction time was 0.50 ms from the ipsilateral and 0.74 ms from the
      contralateral motoneurone pool. Conduction velocities of the axons ranged from
      2.0 to 14.0 ms. The pattern of primary afferent input onto the selected neurones
      was analysed by graded electrical stimulation of dissected trigeminal nerves. Low
      threshold afferents innervating the intraoral mucosa including the tongue and the
      perioral skin of the lower lip were the most effective inputs, as judged from
      both the frequency of occurrence and from the latencies of the evoked spike
      discharges. Ninety-six percent of the neurones responded to stimulation of the
      inferior alveolar nerve (Alv inf) and 83% responded to stimulation of the lingual
      nerve (Ling). The median threshold strength required to evoke the Alv inf and the
      Ling responses was 1.7 T (range 1.0-3.6 T) and 1.3 T (range 1.0-5.0 T),
      respectively. The median latency to spike discharges evoked by the Alv inf was
      2.0 ms (range 1.3-4.8 ms) and to the Ling it was 2.5 ms (range 1.4-7.0 ms).
      Action potentials elicited by stimulation of the masseteric and digastric nerves
      were observed in 40% and 10% of the neurones, respectively. These responses,
      which had median latencies of more than 8 ms (range 4.7-16.0 ms), were only seen
      at stimulation intensities above 2 T (range 2.5-25 T). An input from the
      maxillary whisker nerve was seen in only one case. Postspike averages of the
      extracellular field potentials within the trigeminal motoneurone subnuclei evoked
      by interneuronal spikes were made in a subsample of 51 NVspo-gamma neurones
      activated by iontophoresis of L-glutamic acid. Excitatory synaptic effects within
      the masseteric subnucleus were observed in eight cases. An inhibitory effect was
      seen in one case. One specific neurone gave an excitatory extracellular field
      potential within the digastric motoneurone subnucleus. This interneurone was AD
      activated from the digastric, but not from the masseteric subnucleus.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7589298
TI  - On the form of the internal model for reaching.
AB  - We investigated, by using simulations, possible mechanisms responsible for the
      errors in the direction of arm movements exhibited by deafferented patients. Two
      aspects of altered feedforward control were evaluated: the inability to sense
      initial conditions and the degradation of an internal model. A simulation which
      assumed no compensation for variations in initial arm configuration failed to
      reproduce the characteristic pattern of errors. In contrast, a simulation that
      assumed random variability in the generation of joint torque resulted in a
      distribution of handpaths which resembled some aspects of the pattern of errors
      exhibited by deafferented patients.

PMID- 7589300
TI  - Spatiotemporal stability and patterning of speech movement sequences.
AB  - In order to examine the stability and patterning of speech movement sequences,
      movements of the lip were recorded as subjects produced a phrase at normal, fast,
      and slow rates. Three methods of analysis were employed. First, a new index of
      spatiotemporal stability was derived by summing the standard deviations computed
      across amplitude- and time-normalized displacement records. This index indicated
      that normal and fast rates of speech production result in more stable movement
      execution compared to slow rates. In the second analysis, the relative time of
      occurrence of the peak velocity of the three middle opening movements of the
      utterance was measured. For each of the three peaks, the preservation of relative
      timing was assessed by applying Genter's (1987) slope test. The results clearly
      indicate that the relative timing of these events does not remain constant across
      changes in speech rate. The relative timing of the middle opening gestures
      shifted, becoming later as utterance duration increased. In a third analysis,
      pattern recognition techniques were applied to the normalized displacement
      waveforms. A classification algorithm was highly successful in sorting waveforms
      into normal, fast, and slow rate conditions. These findings were interpreted to
      suggest that, within a subject, three distinct patterns or movement templates
      exist, one for each rate of production. Speech rate appears to be a global
      parameter, one that affects the entire command sequence for the utterance.

PMID- 7589301
TI  - Heading judgments during active and passive self-motion.
AB  - Previous studies have generally considered heading perception to be a visual
      task. However, since judgments of heading direction are required only during self
      motion, there are several other relevant senses which could provide supplementary
      and, in some cases, necessary information to make accurate and precise judgments
      of the direction of self-motion. We assessed the contributions of several of
      these senses using tasks chosen to reflect the reference system used by each
      sensory modality. Head-pointing and rod-pointing tasks were performed in which
      subjects aligned either the head or an unseen pointer with the direction of
      motion during whole body linear motion. Passive visual and vestibular stimulation
      was generated by accelerating subjects at sub- or supravestibular thresholds down
      a linear track. The motor-kinesthetic system was stimulated by having subjects
      actively walk along the track. A helmet-mounted optical system, fixed either on
      the cart used to provide passive visual or vestibular information or on the
      walker used in the active walking conditions, provided a stereoscopic display of
      an optical flow field. Subjects could be positioned at any orientation relative
      to the heading, and heading judgments were obtained using unimodal visual,
      vestibular, or walking cues, or combined visual-vestibular and visual-walking
      cues. Vision alone resulted in reasonably precise and accurate head-pointing
      judgments (0.3 degrees constant errors, 2.9 degrees variable errors), but not rod
      pointing judgments (3.5 degrees constant errors, 5.9 degrees variable errors).
      Concordant visual-walking stimulation slightly decreased the variable errors and
      reduced constant pointing errors to close to zero, while head-pointing errors
      were unaffected.

PMID- 7589299
TI  - Age-related changes in open-loop and closed-loop postural control mechanisms.
AB  - In an earlier posturographic investigation (Collins and De Luca 1993) it was
      proposed that open-loop and closed-loop control mechanisms are involved in the
      regulation of undisturbed, upright stance. In this study, stabilogram-diffusion
      analysis was used to examine how the natural aging process affects the
      operational characteristics of these control mechanisms. Stabilogram-diffusion
      analysis leads to the extraction of repeatable center-of-pressure (COP)
      parameters that can be directly related to the steady-state behavior and
      functional interaction of the neuromuscular mechanisms underlying the maintenance
      of erect posture. Twenty-five healthy young males (aged 19-30 years) and twenty
      five elderly males (aged 71-80 years) who were free of major gait and postural
      disorders were included in the study. An instrumented force platform was used to
      measure the time-varying displacements of the COP under each subject's feet
      during quiet standing. The COP trajectories were analyzed as one-dimensional and
      two-dimensional random walks, according to stabilogram-diffusion analysis. Using
      this technique, it was demonstrated cross-sectionally that healthy aging is
      associated with significant changes in the 'quasi-static' dynamics of the
      postural control system. (It was also shown that more traditional posturographic
      analyses, i.e., summary statistics, were not sensitive enough to detect these age
      related differences.) It was found that the steady-state behavior of the open
      loop postural control mechanisms in the elderly is more positively correlated and
      therefore perhaps more unstable, i.e., the output of the overall system has a
      greater tendency to move or drift away from a relative equilibrium point over the
      short term. In contrast with this result, it was also found that the steady-state
      behavior of the closed-loop postural control mechanisms in the elderly is more
      negatively correlated and therefore perhaps more stable, i.e., over the longer
      term, there is an increased probability that movements away from a relative
      equilibrium point will be offset by corrective adjustments back towards the
      equilibrium position. In addition, it was demonstrated that the elderly utilize
      open-loop control schemes for longer time intervals and correspondingly larger
      COP displacements during periods of undisturbed stance. This result suggests that
      in the elderly there is a greater delay, on average, before closed-loop feedback
      mechanisms are called into play. Finally, it was shown that there is an increased
      heterogeneity of postural control abilities in healthy older adults.

PMID- 7589302
TI  - Origin of P16 median nerve SEP component identified by dipole source analysis-
      subthalamic or within the thalamo-cortical radiation?
AB  - Following median nerve stimulation, several monophasic peaks were recorded at the
      scalp in the 15-18 ms time range. Source analysis, using three different methods,
      modelled a source near the centre of the head with an orientation towards the
      activated hemisphere and a peak activity at 16 ms post stimulus. Magnetic
      recordings detected no signal in this time range, which confirmed a subcortical
      location of the source. From dipole localization it was not possible to assign
      the exact origin of the P16 source to either the subthalamic level or the thalamo
      cortical radiation, because of the limited spatial resolution at the centre of
      the spherical head model. An estimate of the conduction velocity of the medial
      lemniscus pointed towards a subthalamic origin. The P16 source was preserved in
      two patients with a lesion of the thalamo-cortical radiation and the ventral
      thalamus. Further evidence for a subthalamic location of P16 was derived from the
      physical mechanisms generating far-field potentials.

PMID- 7589306
TI  - Modulation of somatocardiac sympathetic reflexes mediated by opioid receptors at
      the spinal and brainstem level.
AB  - Modulation of somatosympathetic reflexes at the spinal cord and the brainstem was
      studied by administering opioid receptor agonists into the intrathecal space of
      the lumbar spinal cord and into the subarachnoid space of the cisterna magna in
      rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A
      and C-reflexes were elicited by electrical stimulation of myelinated (A) and
      unmyelinated (C) afferent fibers of the tibial nerve, respectively. Intrathecal
      administration of the mu-opioid receptor agonist DAMGO selectively depressed the
      C-reflex in a dose-dependent manner (minimum effective dose 10 ng), whereas the
      intrathecal injection of the delta-opioid receptor agonist DPDPE and the kappa
      opioid receptor agonist U-50,488H only at doses of 10 micrograms and 100
      micrograms, respectively, led to a significant depression of the C-reflex.
      Injection of DAMGO into the cisterna magna enhanced both A- and C-reflexes in a
      dose-dependent manner (minimum effective dose 1 ng). The administration of
      neither DPDPE nor U-50,488H into the cisterna magna affected A- or C-reflexes. It
      is concluded that the activation of mu-opioid receptors is mainly or exclusively
      responsible for suppressing somatosympathetic C-reflexes at the spinal cord and
      for enhancing them at the brainstem.

PMID- 7589303
TI  - Auditory and somatosensory event-related brain potentials in early blind humans.
AB  - Previous event-related potential (ERP) studies have suggested a possible
      participation of the visual cortex of the blind in auditory processing. In the
      present study, somatosensory and auditory ERPs of blind and sighted subjects were
      recorded when subjects were instructed to attend to stimuli of one modality and
      to ignore those of the other. Both modalities were stimulated with frequent
      ("standard") and infrequent ("deviant") stimuli, which differed from one another
      in their spatial locus of origin. In the sighted, deviant stimuli of the attended
      modality elicited N2 type of deflections (auditory N2b and somatosensory N250)
      over the lateral scalp areas. In contrast, in the blind, these ERP components
      were centroposteriorly distributed, suggesting an involvement of posterior brain
      areas in auditory and somatosensory stimulus discrimination. In addition, the
      mismatch negativity, elicited by deviant auditory stimuli even when the
      somatosensory stimuli were attended, was larger in the blind than in the sighted.
      This appears to indicate enhanced automatic processing of auditory stimulus
      changes in the blind. Thus, the present data suggest several compensatory changes
      in both auditory and somatosensory modalities after the onset of early visual
      deprivation.

PMID- 7589305
TI  - The auditory pathway in cat corpus callosum.
AB  - The cortical auditory fields of the two hemispheres are interconnected via the
      corpus callosum. We have investigated the topographical arrangement of auditory
      callosal axons in the cat. Following circumscribed biocytin injections in the
      primary (AI), secondary (AII), anterior (AAF) and posterior (PAF) auditory
      fields, labelled axons have been found in the posterior two-thirds of the corpus
      callosum. Callosal axons labelled by small individual cortical injections did not
      form a tight bundle at the callosal midsagittal plane but spread over as much as
      one-third of the corpus callosum. Axons originating from different auditory
      fields were roughly topographically ordered, reflecting to some extent the rostro
      caudal position of the field of origin. Axons from AAF crossed on average more
      rostrally than axons from AI; the latter crossed more rostrally than axons from
      PAF and AII. Callosal axons originating in a discrete part of the cortex
      travelled first in a relatively tight bundle to the telo-diencephalic junction
      and then dispersed progressively. In conclusion, the cat corpus callosum does not
      contain a sector reserved for auditory axons, nor a strictly topographically
      ordered auditory pathway. This observation is of relevance to neuropsychological
      and neuropathological observations in man.

PMID- 7589304
TI  - Hemispheric asymmetry of transcallosal inhibition in man.
AB  - The transcallosal connecting fibres linking corresponding projection areas of the
      same muscles of the right and left primary motor cortex may play an important
      role in control of unilateral movements. It appears that they have mainly
      inhibitory effects. This was further evaluated by transcranial magnetic
      stimulation using two focal coils placed on the optimal positions, i.e. the
      positions with the lowest thresholds at the motor representation areas of the
      first dorsal interosseous muscle of the left and right sides. A conditioning
      stimulus was given to one hemisphere 10 ms prior to the test stimulus at the
      opposite hemisphere. The inhibition was evaluated as relative amplitude
      reduction. Eleven normal right-handed subjects and 11 normal left-handed subjects
      participated in this study. Handedness was evaluated by the Oldfield inventory.
      It was found that in right-handers the inhibition after stimulation of the
      "dominant" left hemisphere was more marked than after stimulation of the "non
      dominant" right hemisphere. In contrast, the group of left-handed subjects showed
      inhomogeneous findings with either right- or left-side predominant inhibition. It
      is concluded that not handedness but hemispheric dominance contributes to the
      laterality of inhibition. The results point to a superior role of the language
      dominant hemisphere in governing inter-hemispheric control of motor cortical
      connections, supporting the view that the "language-dominant" hemisphere is also
      "motor dominant".

PMID- 7589308
TI  - Specific effects of platelet derived growth factor (PDGF) on fetal rat and human
      dopaminergic neurons in vitro.
AB  - The neurotrophic effects of the BB isoform of platelet-derived growth factor
      (PDGF) on rat and human fetal mesencephalic dopaminergic neurons have been
      characterized in vitro. A dose-response analysis demonstrated maximal responses
      at 30 ng/ml of PDGF-BB. This concentration resulted in a marked increase in the
      survival and neurite outgrowth from rat and human tyrosine hydroxylase-(TH)
      positive, presumed dopaminergic neurons after 7 days in vitro. The effects of
      PDGF-BB on survival of TH-positive neurons were comparable to those of brain
      derived neurotrophic factor (BDNF), whereas neurite outgrowth was more pronounced
      after addition of BDNF. The combination of BDNF and PDGF-BB yielded no additive
      effects. Double immunohistochemical staining of rat cultures demonstrated PDGF
      beta-receptors on about 90% of the TH-positive neurons. PDGF-BB treatment of rat
      mesencephalic cultures induced an upregulation of c-fos and TH mRNA with maximal
      levels after 0.5-2 h as assessed by quantitative PCR analysis. An increased
      number of Fos protein-positive cells was detected immunohistochemically after 4 h
      of PDGF-BB treatment. The present results provide further evidence for specific
      and direct effects of PDGF-BB on gene expression, survival and neurite outgrowth
      of mesencephalic dopaminergic neurons of rat and human origin.

PMID- 7589307
TI  - Role of somatosensory and vestibular cues in attenuating visually induced human
      postural sway.
AB  - The purpose of this study was to determine the contribution of visual,
      vestibular, and somatosensory cues to the maintenance of stance in humans.
      Postural sway was induced by full-field, sinusoidal visual surround rotations
      about an axis at the level of the ankle joints. The influences of vestibular and
      somatosensory cues were characterized by comparing postural sway in normal and
      bilateral vestibular absent subjects in conditions that provided either accurate
      or inaccurate somatosensory orientation information. In normal subjects, the
      amplitude of visually induced sway reached a saturation level as stimulus
      amplitude increased. The saturation amplitude decreased with increasing stimulus
      frequency. No saturation phenomena were observed in subjects with vestibular
      loss, implying that vestibular cues were responsible for the saturation
      phenomenon. For visually induced sways below the saturation level, the stimulus
      response curves for both normal subjects and subjects experiencing vestibular
      loss were nearly identical, implying (1) that normal subjects were not using
      vestibular information to attenuate their visually induced sway, possibly because
      sway was below a vestibular-related threshold level, and (2) that subjects with
      vestibular loss did not utilize visual cues to a greater extent than normal
      subjects; that is, a fundamental change in visual system "gain" was not used to
      compensate for a vestibular deficit. An unexpected finding was that the amplitude
      of body sway induced by visual surround motion could be almost 3 times greater
      than the amplitude of the visual stimulus in normal subjects and subjects with
      vestibular loss. This occurred in conditions where somatosensory cues were
      inaccurate and at low stimulus amplitudes. A control system model of visually
      induced postural sway was developed to explain this finding. For both subject
      groups, the amplitude of visually induced sway was smaller by a factor of about 4
      in tests where somatosensory cues provided accurate versus inaccurate orientation
      information. This implied (1) that the subjects experiencing vestibular loss did
      not utilize somatosensory cues to a greater extent than normal subjects; that is,
      changes in somatosensory system "gain" were not used to compensate for a
      vestibular deficit, and (2) that the threshold for the use of vestibular cues in
      normal subjects was apparently lower in test conditions where somatosensory cues
      were providing accurate orientation information.

PMID- 7589312
TI  - Effects of unilateral brain damage on the control of goal-directed hand
      movements.
AB  - Insight into the functional neural substrates associated with the control of goal
      directed purposive movements can be obtained through the study of the performance
      of individuals with brain damage. The control of rapid reciprocal aiming was
      investigated by comparing ipsilateral limb performance of subjects with
      unilateral brain damage to that of controls performing with the same limb. Thirty
      right-hand-dominant individuals, ten with right hemisphere stroke, ten with left
      hemisphere stroke, and ten age-matched controls performed unconstrained
      alternating tapping movements under three conditions of task complexity. The path
      of the stylus was recorded by video using two-dimensional kinematic techniques.
      Key kinematic features of the vertical and horizontal components of the
      trajectories were analyzed using both quantitative and qualitative methods. All
      subjects with brain damage showed prolonged movement times; however, the locus of
      the slowing depended on lesion side. Specifically, subjects with left stroke
      showed deficits in the open-loop component of the movement across all three
      conditions of task complexity, and a prolonged reversal phase surrounding target
      impact, particularly in the most complex condition. In contrast, subjects with
      right stroke showed deficits in the closed-loop phase of the movement prior to
      target impact, particularly in the most complex condition when visual information
      was necessary for accuracy. Together, these results suggest that for the control
      of rapid goal-directed aiming movements, the left hemisphere is dominant for task
      relevant aspects of processing associated with the ballistic component and the
      timing or triggering of sequential movements. In contrast, the right hemisphere
      is dominant for processing associated with rapid, on-line visual information even
      when target location is known and direction is certain.

PMID- 7589310
TI  - Hand muscle reflexes following air puff stimulation.
AB  - Hand muscle reflexes following muscle stretch and electrical nerve stimulation
      show a typical pattern consisting of short- and long-latency reflexes. The
      present investigation was designed to test reflexes following pure cutaneous
      stimulation. Air puffs were delivered to the palmar tip and the nail bed of the
      first, second and fifth fingers during isotonic contraction of hand muscles. The
      EMGs from the thenar muscles, the first dorsal interosseous muscle and the
      hypothenar muscles were recorded. Reflexes were obtained in all muscles, with a
      typical configuration consisting of a short-latency excitatory component
      (cutaneous long-latency reflex I, cLLR I) and a second excitatory component
      (cutaneous long-latency reflex II, cLLR II), with an inhibitory component between
      them. The size of cLLR II differed depending on the area stimulated and the
      muscle recorded. We found the largest responses always in the muscle acting on
      the stimulated finger. The reflex size depended on the strength of air puff
      stimulation. Allowing small displacements of the fingers led to an additional
      increase in the size of the reflex. The pattern of reflexes was identical
      independent of whether the finger tip or the nail bed was stimulated, but the
      size of the reflexes was smaller following nail bed stimulation. Following
      blockade of the cutaneous nerve branches of the thumb with local anaesthetics,
      air puff stimulation of the thumb no longer elicited this reflex pattern. Hence,
      under our experimental conditions, cutaneous receptors were the only source of
      afferent input for these reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589311
TI  - The internal control of action and Parkinson's disease: a kinematic analysis of
      visually-guided and memory-guided prehension movements.
AB  - This paper reports two experiments which examined the effects of Parkinson's
      disease (PD) upon the sensorimotor mechanisms used to control prehension
      movements. Transport and grasp kinematics for visually-guided and memory-guided
      prehension movements were examined in healthy control subjects and compared
      against those of patients with idiopathic PD. Two research questions were
      addressed: (1) Are patients with PD particularly susceptible to distraction by
      non-relevant objects? (2) Are patients with PD especially reliant on external
      feedback when executing goal-directed actions? The results indicated that the
      patient group were no more susceptible to distraction by non-relevant objects
      than the control group. In contrast, the patients with PD were shown to be
      significantly impaired when executing memory-guided reaches. Furthermore, the
      deficits exhibited by the PD group on memory-guided reaches were confined solely
      to those markers associated with the transport component of the prehension
      movement. That is, while both controls and patients with PD widened their grip
      aperture on memory-guided trials, the magnitude of this adjustment was comparable
      across the two groups. The implications of these findings for theories of
      visuomotor processing in sufferers of PD and the control of prehension movements
      more generally are discussed.

PMID- 7589309
TI  - Coordination of multiple muscles in two degree of freedom elbow movements.
AB  - The present study quantifies electromyographic (EMG) magnitude, timing, and
      duration in one and two degree of freedom elbow movements involving combinations
      of flexion-extension and pronation-supination. The aim is to understand the
      organization of commands subserving motion in individual and multiple degrees of
      freedom. The muscles tested in this study fell into two categories with respect
      to agonist burst magnitude: those whose burst magnitude varied with motion in a
      second degree of freedom at the elbow, and those whose burst magnitude depended
      on motion in one degree of freedom only. In multiarticular muscles contributing
      to motion in two degrees of freedom at the elbow, we found that the magnitude of
      the agonist burst was greatest for movements in which a muscle acted as agonist
      in both degrees of freedom. The burst magnitudes for one degree of freedom
      movements were, in turn, greater than for movements in which the muscle was
      agonist in one degree of freedom and antagonist in the other. It was also found
      that, for movements in which a muscle acted as agonist in two degrees of freedom,
      the burst magnitude was, in the majority of cases, not different from the sum of
      the burst magnitudes in the component movements. When differences occurred, the
      burst magnitude for the combined movement was greater than the sum of the
      components. Other measures of EMG activity such as burst onset time and duration
      were not found to vary in a systematic manner with motion in these two degrees of
      freedom. It was also seen that several muscles which produced motion in one
      degree of freedom at the elbow, including triceps brachii (long head), triceps
      brachii (lateral head), and pronator quadratus displayed first agonist bursts
      whose magnitude did not vary with motion in a second degree of freedom. However,
      for the monoarticular elbow flexors brachialis and brachioradialis, agonist burst
      magnitude was affected by pronation or supination. Lastly, it was observed that
      during elbow movements in which muscles acted as agonist in one degree of freedom
      and antagonist in the other, the muscle activity often displayed both agonist and
      antagonist components in the same movement. It was found that, for pronator teres
      and biceps brachii, the timing of the bursts was such that there was activity in
      these muscles concurrent with activity in both pure agonists and pure
      antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7589313
TI  - Uncinate fascicle section leaves delayed matching-to-sample intact, with both
      large and small stimulus sets.
AB  - An earlier study found that rhinal cortex ablations in the monkey (Macaca
      fascicularis) impaired delayed matching-to-sample only when the stimuli in the
      experiment came from a large population of possible stimuli, not when the
      stimulus population was small. The present experiment tested the idea that
      delayed matching-to-sample with a small stimulus population selectively engages
      the direct projection from visual association cortex to the prefrontal cortex,
      bypassing the rhinal cortex. This selective involvement could explain the
      preservation, after rhinal cortex ablations, of memory for items drawn from a
      small stimulus population. We trained monkeys preoperatively in delayed matching
      to-sample with large and small stimulus populations, exactly as in the earlier
      study, then examined the effect of sectioning the cortico-cortical pathway
      between visual association cortex and prefrontal cortex, the uncinate fascicle.
      Uncinate fascicle section had no effect on postoperative performance of delayed
      matching-to-sample, with either large or small stimulus populations. These data
      give no support to the idea that preserved matching with a small stimulus
      population after rhinal lesions reflects the selective involvement in this task
      of the direct projection from visual association cortex to prefrontal cortex.
      Further, they strengthen the idea (derived from earlier studies of uncinate
      fascicle section) that the uncinate fascicle does not play a general role in
      visual memory or perception, but instead has a specialized function in the
      processing of conditional instruction cues.

PMID- 7589314
TI  - Effects of histamine and betahistine on rat medial vestibular nucleus neurones:
      possible mechanism of action of anti-histaminergic drugs in vertigo and motion
      sickness.
AB  - The tonic discharge of 71 medial vestibular nucleus (MVN) neurones was recorded
      in slices of the dorsal brainstem of young adult rats. Bath application of
      histamine caused a dose-related excitation in 59 of the 71 cells (83%), the
      remaining 12 (17%) being unresponsive. Dimaprit, a selective H2 agonist, also
      caused excitation in all 20 cells tested. The histamine-induced excitation and
      the response to dimaprit were antagonised by the selective H2 antagonist
      ranitidine, confirming that the H2 subtype of histamine receptor is involved in
      mediating the effects of histamine on these cells. Triprolidine, a selective H1
      antagonist, also antagonised the excitation caused by histamine, at a
      concentration (0.3 microM) which left the H2 receptor-mediated response to
      dimaprit unchanged. Thus the excitatory effects of histamine on MVN cells in the
      rat involve two components mediated through H1 and H2 receptor-linked mechanisms,
      respectively. Betahistine, a weak H1 agonist and H3 antagonist, had little
      excitatory action when applied on its own, but significantly reduced the
      excitation caused by histamine when the two drugs were applied together. The
      effects of betahistine were consistent with a partial-agonist action at H1
      receptors on MVN cells, reducing the excitatory responses to histamine presumably
      by occupying these receptor sites in competition with the exogenously applied
      neurotransmitter. This partial-agonist action of betahistine may be an important
      part of its mechanism of action in the symptomatic treatment of vertigo and
      motion sickness, since it is likely to occur not only in the MVN but also in many
      brain regions, including the thalamus and cortex, which express H1 receptors and
      which are innervated by the hypothalamic histaminergic system. Thus the
      effectiveness of betahistine and other anti-H1 drugs against motion sickness may
      be explained by their action in reducing the effects of the excess histamine
      release induced in such conditions in various brain areas, including the MVN.

PMID- 7589315
TI  - Depression of transmission from group II muscle afferents by electrical
      stimulation of the cuneiform nucleus in the cat.
AB  - The effects of short trains of electrical stimuli applied within the cuneiform
      nucleus and the subcuneiform region were examined on transmission from group I
      and group II muscle afferents to first-order spinal neurons. Variations in the
      effectiveness of transmission from these afferents were assessed from changes in
      the sizes of the monosynaptic component of extracellular field potentials evoked
      following stimulation of muscle nerves. Field potentials evoked from group II
      muscle afferents in the dorsal horn of the midlumbar and sacral segments and in
      the intermediate zone of the midlumbar segments were reduced when the test
      stimuli applied to peripheral nerves were preceded by conditioning stimulation of
      the cuneiform nucleus or the subcuneiform region. The depression occurred at
      conditioning-testing intervals of 20-400 ms, being maximal at intervals of 32-72
      ms for dorsal horn potentials and 40-100 ms for intermediate zone potentials. At
      the shortest intervals, both group II and group I field potentials in the
      intermediate zone were depressed. Conditioning stimulation of the cuneiform
      nucleus depressed group II field potentials nearly as effectively as conditioning
      stimulation of the coerulear or raphe nuclei. We propose that the nonselective
      depression of transmission from group I and II afferents at short intervals is
      due to the activation of reticulospinal pathways by cells or fibers stimulated
      within the cuneiform area. We also propose that the selective depression of
      transmission from group II afferents at long intervals is mediated at least
      partly by monoaminergic pathways, in view of the similarity of the effects of
      conditioning stimulation of the cuneiform nucleus and of the brainstem
      monoaminergic nuclei and by directly applied monoamines (Bras et al. 1990). In
      addition, it might be caused by primary afferent depolarization mediated by non
      monoaminergic fibers (Riddell et al. 1992).

PMID- 7589316
TI  - Dopaminergic control of transmission from group II muscle afferents to spinal
      neurones in the cat and guinea-pig.
AB  - The effects of dopamine and its agonists on transmission from muscle afferents to
      spinal neurones were investigated in the cat and guinea-pig spinal cord, by
      measuring the drug effects on the amplitude of monosynaptic field potentials
      evoked by electrical stimulation of group I and group II muscle afferents. Local
      iontophoretic application of dopamine, the dopamine D1/D5 agonist SKF-38393 and
      the D2/D3/D4 agonist quinpirole all depressed the group II field potentials
      evoked at the base of the dorsal horn. Group II field potentials in the
      intermediate zone were depressed by dopamine to a similar degree as the dorsal
      horn field potentials, whereas the dopamine agonists were without effect upon
      them. The intermediate zone field potentials evoked by group I muscle afferents
      were not depressed by any of the drugs. The dopamine-evoked depression of the
      group II-evoked field potentials in the dorsal horn in the guinea-pig spinal cord
      was reduced by the simultaneous application of haloperidol. The results
      demonstrate that dopamine receptors mediate the depression of transmission from
      group II muscle afferents to interneurones in the dorsal horn, but not to
      neurones in the intermediate zone of the spinal cord.

PMID- 7589317
TI  - Reduction of apomorphine-induced rotational behaviour by subthalamic lesion in 6
      OHDA lesioned rats is associated with a normalization of firing rate and
      discharge pattern of pars reticulata neurons.
AB  - The effect of subthalamic nucleus (STh) lesion on apomorphine-induced rotational
      behaviour and unit activity of substantia nigra pars reticulata (SNr) neurons was
      studied in normal, sham-control and unilateral 6-OHDA-lesioned rats [SN pars
      compacta (SNc)-lesioned]. In the latter, contraversive rotational behaviour was
      greatly reduced by an additional ipsilateral STh lesion. A moderate ipsiversive
      rotation was observed in rats with a single STh lesion. Concurrently, SN unit
      extracellular recordings were performed in age-matched normal rats, sham-controls
      for both lesions, STh-lesioned rats, SNc-lesioned rats, and SNc-lesioned rats
      with an ipsilateral STh lesion (SNc+STh-lesioned). Pars reticulata neurons had a
      higher mean firing rate in SNc-lesioned rats than in control rats. Furthermore,
      68% of SNr neurons in SNc-lesioned rats had a tonic discharge pattern (against
      92.3% in control rats) and 32% a mixed or bursting pattern. After STh lesion, a
      clear decrease in SNr firing rate was observed in SNc-lesioned rats. Moreover,
      STh lesion improved interspike interval regularity and decreased the occurrence
      of bursting patterns. In rats with a single STh lesion, the firing rate was no
      different from that of the sham-controls but the discharge pattern was more
      regular. These data show that STh lesion decreased apomorphine-induced rotational
      behaviour in dopamine-depleted animals. This effect could be related to the
      suppression of the excitatory effect of STh efferents on the SNr neurons. STh
      lesion both counterbalanced the increased activity of SNr neurons and regularized
      their discharge pattern.

PMID- 7589318
TI  - Transplantation of embryonic retinal donor cells labelled with BrdU or carrying a
      genetic marker to adult retina.
AB  - After transplantation of embryonic retinal cells to injured adult retina, it is
      often difficult to distinguish donor from host cells. To overcome this problem,
      two methods were applied: labelling donor cells with the nuclear marker
      bromodeoxyuridine (BrdU) and use of transgenic donor tissue. BrdU was injected
      into timed-pregnant rats on 2 or 3 consecutive days. The donor embryos were taken
      1-4 days later for transplantation. The BrdU-labelled donor tissue was examined
      in transplants sampled up to 1 year after grafting. Labelled donor cells were
      specifically identified in the transplants and in the interface with the adjacent
      host retina. The varying intensities of cell labelling indicated differences in
      the initial uptake of BrdU in the S-phase, or the dilution of the label by cell
      divisions after BrdU injection. The best labelled cells were presumably the ones
      that stopped dividing shortly after injection of BrdU. As controls, the normal
      development of BrdU-labelled retinas from the offspring of females that had been
      BrdU-injected at E16 and E17 and not used for transplantation was studied. Near
      the time of birth, clones of labelled cells were radially distributed. In the
      mature retina, labelled cells were seen in all retinal layers. Embryonic retina
      derived from transgenic (NSE-lacZ) mice was transplanted to 'nude',
      immunodeficient rats (xenografts). These transgenic mice contain the Escherichia
      coli beta-galactosidase gene, coupled to the promoter for neuron-specific enolase
      (NSE). Thus, all retinal donor cells that contain NSE could be identified by
      histochemistry or immunohistochemistry. The donor cells expressing the transgene
      could be detected several months after transplantation.

PMID- 7589319
TI  - Transmission characteristics for the 1:1 linkage between slowly adapting type II
      fibers and their cuneate target neurons in cat.
AB  - Transmission from single, identified, slowly adapting type II (SAII) tactile
      fibers to their target neurons in the cuneate nucleus was examined in
      anesthetized cats. Simultaneous recordings were made from cuneate neurons and
      from fine, intact fascicles of the superficial radial nerve in which it was
      possible to identify and monitor the activity of each group II fiber. Selective
      activation of individual SAII fibers was achieved by means of skin stimulation
      with fine probes, in conjunction with extensive forelimb denervation. Responses
      were studied for seven SAII-driven cuneate neurons. For three there was
      unequivocal monitoring of the identified SAII input fiber. However, in six of the
      seven there was evidence that just one SAII fiber provided suprathreshold input
      to the cuneate neuron, and neither temporal nor spatial summation was required
      for reliable transmission. Cuneate impulse rates, in response to SAII inputs
      lasting 1 s, were less than 250 impulses per second, even though the SAII impulse
      rates could be 500 s-1. Responses to individual SAII impulses consisted of a
      burst of 2-3 impulses at low SAII input rates, but burst responses disappeared at
      high SAII rates. In all three SAII-cuneate pairs studied, the transmission
      security (the percentage of SAII impulses that evoked cuneate spike output)
      exceeded 80% in response to static skin displacement and in response to certain
      frequencies of skin vibration, in particular, at 100-200 Hz, exceeded 98% when
      the SAII fiber responded near the 1:1 level (one impulse per vibration
      cycle).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589320
TI  - Latency variability of responses to visual stimuli in cells of the cat's lateral
      geniculate nucleus.
AB  - We constructed average histograms from responses evoked by flashing stimuli and
      noted previously described variations in the shape of the response profile,
      particularly with respect to sharpness of the peak. To express this variable, we
      measured the half-rise latency, which is the latency from stimulus onset required
      to reach half the maximum response. A short half-rise latency, which is
      characteristic of nonlagged cells, is associated with a brisk response and sharp
      peak; a long half-rise latency, characteristic of lagged cells, is associated
      with a sluggish response and broad peak. Nonlagged cells were readily seen; we
      attempted to identify cells with long latencies as lagged, but we were unable to
      do so unambiguously due to failure to observe lagged properties other than
      latency. We thus refer to these latter cells as having "lagged-like" responses to
      indicate that we are not certain whether these are indeed lagged cells. In
      addition to the histograms, we analyzed the individual response trials that were
      summed to create each histogram, and we used spike density analysis to estimate
      the initial response latency to the flashing spot for each trial. We found that
      lagged-like responses were associated with more variability in initial response
      latency than were nonlagged responses. We then employed an alignment procedure to
      eliminate latency variation from individual trials; that is, responses during
      individual trials were shifted in time as needed so that each had a latency equal
      to the average latency of all trials. We used these "aligned" trials to create a
      second, "aligned" response histogram for each cell. The alignment procedure had
      little effect on nonlagged responses, because these were already well aligned due
      to consistent response latencies amongst trials. For lagged-like responses,
      however, the alignment made a dramatic difference. The aligned histograms looked
      very much like those for nonlagged responses: the responses appeared brisk, with
      a sharply rising peak that was fairly high in amplitude. We thus conclude that
      the slow build up to a relatively low peak of firing of the lagged-like response
      histogram is not an accurate reflection of responses on single trials. Instead,
      the sluggishness of lagged-like responses inferred from average response
      histograms results from temporal smearing due to latency variability amongst
      trials. We thus conclude that there is relatively little difference in briskness
      between nonlagged and lagged-like responses to single stimuli.

PMID- 7589321
TI  - Embryonic striatal grafts reverse the disinhibitory effects of ibotenic acid
      lesions of the ventral striatum.
AB  - Bilateral damage to the ventral striatum induced by the excitotoxin ibotenic acid
      was found to have profound disinhibitory effects on rats' behaviour. Lesioned
      animals were unable to acquire efficient levels of performance on an operant
      schedule (differential reinforcement of low rates of responding, DRL) that
      required them to inhibit a previously rewarded response. In addition, lesioned
      subjects were relatively resistant to the disruptive effects of amphetamine on
      performance of the DRL schedule and were slower to cease responding under
      conditions of non-reward. A measure of unconditioned behaviour, overnight
      locomotor activity, was also disinhibited by the presence of the lesion. Grafts
      of embryonic striatal tissue transplanted to the lesioned ventral striatum were
      found to survive well. Moreover, the presence of the grafts reversed the effects
      of the lesion on measures of conditioned and unconditioned behaviour. The nature
      of the lesion-induced behavioural deficit and the ability of the embryonic
      transplants to reverse it are discussed in terms of the possible restoration of
      limbi-subcortical circuitry.

PMID- 7589323
TI  - Development of locomotor behavior in the spinal kitten.
AB  - This study was undertaken to determine the locomotor capability of kittens whose
      spinal cords were transected at birth. The postnatal development of reflex and
      goal-directed locomotion was examined during the first 5 postnatal months in
      kittens that received low thoracic spinal cord transections as newborns. Some
      spinal kittens developed aberrant quadrupedal forms of locomotion. The onset of
      quadrupedal locomotion, however, was delayed by 2-3 months compared to the normal
      kitten (42) and deteriorated by 5 months of age. Qualitative and quantitative
      analyses demonstrated that the quadrupedal locomotion was abnormal. Although some
      step cycles were characterized by full weight support, the typical hindlimb step
      cycle of the best performing cat showed inadequate weight support and balance. No
      spinal cat was able to coordinate the hindlimbs with the forelimbs during
      overground locomotion on a runaway or during quadrupedal locomotion on a
      treadmill. Neuroanatomical tracing with WGA-HRP and immunocytochemical techniques
      showed no axonal regeneration or growth into or across the lesion sites. The
      aberrant form of quadrupedal locomotion developed without descending input to the
      caudal spinal cord. The variability in performance among animals suggested that
      compensatory strategies were important factors in the spinal kitten's achievement
      of quadrupedal locomotion. Hindlimb weight-supported stepping during quadrupedal
      locomotion in some animals underscored the capacity of the isolated caudal spinal
      cord to generate both rhythmical stepping movements and weight support. The
      maintenance of developmentally immature, but functional, hindlimb postures
      suggested that the development of the isolated caudal spinal cord was arrested in
      the absence of descending input.

PMID- 7589322
TI  - NMDA and non-NMDA receptors contribute to synaptic transmission between the
      medial geniculate body and the lateral nucleus of the amygdala.
AB  - We examined whether the NMDA class of excitatory amino acid receptors contribute
      to synaptic transmission in the pathway connecting the medial geniculate body
      (MGB) with the lateral nucleus of the amygdala (LA) using extracellular single
      unit recordings and microiontophoresis. Cells were identified in LA on the basis
      of responsivity to electrical stimulation of the MGB. For each cell, a level of
      current was found for the iontophoretic ejection of the NMDA antagonist AP5 that
      blocked responses elicited by iontophoresis of NMDA, but had no effect on
      responses elicited by AMPA. Iontophoresis of AP5 with this level of current
      blocked the excitatory response elicited by MGB stimulation in most cells tested.
      Microinfusion of AP5 (25, 50, or 100 microM) also blocked the responses.
      Additional studies tested individual cells with both AP5 and the AMPA antagonist
      CNQX and showed that blockade of either NMDA or AMPA receptors interferes with
      synaptic transmission. Finally, iontophoretic ejection of either AP5 or CNQX
      blocked short-latency (< 25 ms) responses elicited in LA by peripheral auditory
      stimulation. Together, these results suggest that the synaptic evocation of
      action potentials in the thalamo-amygdala pathway depends on both NMDA and non
      NMDA receptors. We hypothesize that non-NMDA receptors are most likely required
      to depolarize the cell sufficiently to remove the blockade of NMDA channels by
      magnesium and NMDA receptors are required to further depolarize the membrane to
      the level required for action potential generation.

PMID- 7589325
TI  - Protective role of nerve growth factor against excitatory amino acid injury
      during neostriatal cholinergic neurons postnatal development.
AB  - The interaction between excitatory amino acids (EAAs) and nerve growth factor
      (NGF) levels were studied on neostriatal cholinergic neurons during postnatal
      development. Striatal choline acetyltransferase (ChAT) activity and NGF levels
      were determined 7 days following EAA injection in 7-, 15-, 21-, 30-, and 50-day
      old rats. ChAT activity was decreased 7 days after kainate (KA), quinolinate
      (QUIN), or quisqualate (QUIS) lesion. The reduction was most pronounced in 30-day
      old rats. KA injection produced the greatest decrease in ChAT activity.
      Conversely, KA did not change NGF levels. QUIN and QUIS increased NGF protein and
      these effects were maximal with lesions in 21-day-old rats. In order to further
      characterize the effect of EAAs on NGF levels and ChAT activity, the time-course
      of the lesion was studied. We used 30-day-old rats as the maximal sensitivity of
      cholinergic neurons to EAAs was observed at this age. ChAT activity decreased 2
      days following QUIN or QUIS injection and 1 day after KA. The EAA agonists also
      changed NGF levels. QUIN induced an increase in NGF levels 1 day after lesion.
      This effect was maintained to the last time point examined. In contrast, KA and
      QUIS induced transient increases in NGF levels that were only detected 2 and 4
      days after injection, respectively. To study whether NGF is able to regulate EAA
      excitotoxicity on striatal cholinergic neurons, we studied ChAT activity 7 days
      after simultaneous injection of NGF plus QUIN, KA, or QUIS. Intrastriatal
      injection of exogenous NGF was able to block the decrease in ChAT activity
      observed following EAA injection alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589324
TI  - Transplants enhance locomotion in neonatal kittens whose spinal cords are
      transected: a behavioral and anatomical study.
AB  - We have studied the locomotor development of kittens that received complete low
      thoracic spinal cord transections and embryonic spinal cord transplants as
      newborns. Embryonic spinal cord (E21-E26) transplanted into the site of a
      transection integrated well with the host spinal cord and promoted the
      development of overground locomotion. Spinalized kittens with transplants were
      first distinguished from spinalized kittens during the 2nd and 3rd postnatal
      weeks when kittens with transplants positioned their hindlimbs underneath their
      bodies which promoted support of the hindquarters. By postnatal Week 6, kittens
      with transplants exhibited overground locomotion characterized by full weight
      support and moderate balance control. By 20 weeks of age, as many as 96% of the
      step cycles showed full weight support and as few as 2% of the step cycles were
      interrupted by a fall. Most kittens also showed coordination between the
      forelimbs and the hindlimbs. They differed from normal in the precocious onset of
      reflex stepping and in the less precise interlimb coordination and more
      precarious balance during overground locomotion. The overground locomotor
      performance of kittens with transplants greatly exceeded that of spinal kittens
      without transplants since few spinalized kittens showed any full-weight-supported
      step cycles and none showed coordination between the forelimbs and the hindlimbs.
      In the absence of a transplant, no fibers could grow across the lesion site. In
      the presence of a transplant, fibers grew across the lesion site and established
      anatomical connectivity with the host. Host segmental systems identified by the
      presence of calcitonin gene-related peptide- and substance P-immunoreactive
      fibers were found throughout the transplants. Descending host systems of
      supraspinal origin were identified by serotonin- and dopamine beta-hydroxylase
      immunoreactive fibers throughout the transplants. The growth of supraspinal axons
      into the transplant, and in one case into the caudal host spinal cord, provided a
      possible anatomical basis for the development of coordinated overground
      locomotion.

PMID- 7589328
TI  - The development of quadrupedal locomotion in the kitten.
AB  - The development of bipedal treadmill locomotion and overground locomotion has
      previously been studied in the kitten; the development of quadrupedal treadmill
      locomotion has not. We evaluated and compared all three forms of locomotion in
      the normal kitten and present quantitative data comparing the development of
      quadrupedal treadmill and overground locomotion. Overground locomotion was
      studied from the day of birth to 5 months of age and quadrupedal treadmill
      locomotion was studied in the same animals from 9 weeks to 5 months of age.
      Treadmill locomotion was initiated postweaning, since it could not be reliably
      elicited without a food reward. Three locomotor characteristics (weight support,
      balance, and coordination between the forelimbs and the hindlimbs) were evaluated
      quantitatively. Kittens first consistently demonstrated overground steps with the
      ventral surface of their bodies supported above the walking surface throughout
      the entire step cycle during the second and third postnatal weeks. By 4 weeks of
      age, overground locomotion consistently showed full weight support and midline
      positioning of the hindquarters. Coordination between the forelimbs and the
      hindlimbs developed differently in the two forms of quadrupedal locomotion
      evaluated. During overground locomotion, the kittens initially used a single
      pattern in which only one limb was in swing at any time. As the kittens' weight
      support and trunk control improved, additional swing phase coordination patterns
      emerged and these patterns were correlated with the animals' ability to change
      speeds during locomotion. The consistency with which a dominant interlimb swing
      phase pattern was used at a particular speed increased with age and, by 6 weeks,
      the frequency of each speed-related dominant pattern approached 100% during
      overground locomotion. At 6 weeks, interlimb coordination also was evident in the
      nearly consistent interlimb phase interval present between the forelimb's
      initiation of the first extension subphase and the ipsilateral hindlimb's
      initiation of the flexion phase. The consistent patterns appeared to be fostered
      by maturation of weight support and balance. In contrast, the interlimb phase
      interval was inconsistent during quadrupedal treadmill locomotion until 20 weeks
      of age. Moreover, the interlimb swing phase patterns used during quadrupedal
      treadmill locomotion differed from those used during overground locomotion. The
      differences in the developmental time course and patterns of interlimb
      coordination between overground and quadrupedal treadmill locomotion suggest that
      different mechanisms regulate the control of interlimb coordination during these
      two different forms of quadrupedal locomotion.

PMID- 7589327
TI  - Localization of Mu and delta opioid receptors to anterior cingulate afferents and
      projection neurons and input/output model of Mu regulation.
AB  - Anterior cingulate cortex (ACC) has one of the highest densities of opioid
      receptors in the CNS and it has been implicated in acute and chronic pain
      responses. Little is known, however, about which neurons express opioid receptors
      in their dendrites and axon terminals. The present studies employed experimental
      techniques to remove afferent axons or classes of projection neurons from rat ACC
      area 24 followed by coverslip autoradiography to localize changes in binding of
      [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO) to mu receptors and 2-[3H]D-penicillamine
      5-D-penicillamine-enkephalin (DPDPE) to delta receptors. Removal of all afferents
      to area 24 with undercut lesions did not alter DPDPE binding, but significantly
      reduced binding of DAMGO in layers I, III, and V. In contrast, removal of all
      cortical neurons with the excitotoxin ibotenic acid almost abolished DPDPE
      binding in all layers. The same lesions reduced DAMGO binding in most layers;
      however, there was a postlesion bimodal distribution in binding with high levels
      of binding in layer I and moderate levels in layer VI. These data suggest that
      delta receptors are expressed by cortical neurons, while mu receptors are
      expressed by both cortical neurons and afferent axons. To explore the
      distribution of postsynaptic receptors, immunotoxin lesions were made in area 24
      by injection of OX7-saporin into the caudate and/or thalamic nuclei. Almost
      complete removal of projection neurons to these targets in layers Vb and VIa did
      not alter DPDPE binding, while the lesions reduced DAMGO binding in all but layer
      II. Removal of layer Vb corticostriatal projection neurons with caudate OX7
      saporin injections reduced binding only in this layer. It is proposed that
      opioidergic circuits in area 24 are organized according to an input/output model
      for mu opioid regulation. In this model mu receptors regulate axon terminal
      activity from the thalamus in layer Ia and the locus coeruleus in layers Ic and
      II, whereas cortical outputs to the thalamus are modulated via postsynaptic
      receptors expressed in all layers by thalamocortical projection neurons with
      somata in layer VI. These opioidergic circuits in ACC are of particular
      importance because they may regulate responses to chronic nociceptive activity
      and associated pain perceptions.

PMID- 7589330
TI  - Characterization of histaminergic H3 receptors in intraocular tuberomammillary
      transplants containing histaminergic neurons.
AB  - This study was performed to investigate the physicological properties of
      histaminergic neurons in intraocular hypothalamic transplants. Pieces of
      posterolateral hypothalamus containing the tuberomammillary nucleus were
      dissected from Embryonic Day 17 rat fetuses and transplanted into the anterior
      chamber of the eye of adult rat hosts. The hypothalamic transplants were left to
      mature for 2-5 months, after which in vivo electrophysiological recordings were
      performed. Extracellular recordings revealed spontaneously active neurons in the
      grafts, with a mean (+/- SEM) firing rate of 2.8 +/- 2.0 Hz and a mean action
      potential duration of 1.2 +/- 0.5 ms. When the surface of the grafts was
      superfused with histamine, the neuronal activity was depressed at concentrations
      above 30 microM. Superfusion with the H3 agonist (R)-alpha-methylhistamine also
      elicited depression of baseline firing rate, with an EC50 of 0.435 microM. This
      depression could be antagonized by superfusion with the H3-receptor antagonist
      thioperamide. In studies of histamine levels using a sensitive radioenzymatic
      assay, the mean (+/- SEM) level of histamine in the grafts was 73 +/- 28 ng/g
      tissue, i.e., about half the concentration of histamine in the adult rat
      hypothalamus in situ. Intracellular recordings in combination with biocytin
      labeling and histidine decarboxylase immunohistochemistry suggested that the
      grafted neurons from which recordings were made were histaminergic. Taken
      together, these data indicate that tuberomammillary neurons continue their
      development in intraocular transplants and develop physiological characteristics
      found in these neurons in situ.

PMID- 7589326
TI  - Staurosporine-induced neuronal apoptosis.
AB  - Staurosporine, a nonselective protein kinase inhibitor, has been shown to induce
      apoptosis in several different nonneuronal cell types. We tested the hypothesis
      that staurosporine would also induce apoptosis in central neurons. Exposure of
      murine cortical cell cultures to 30-100 nM staurosporine induced concentration
      dependent selective neuronal degeneration over the following day; at higher
      concentrations, staurosporine damaged glial cells as well. Staurosporine-induced
      neuronal death was accompanied by cell body shrinkage, chromatin condensation,
      and DNA laddering. In contrast, NMDA-induced neuronal death was accompanied by
      acute cell body swelling without DNA laddering. Staurosporine-induced neuronal
      death, unlike excitotoxic death, was markedly attenuated by the protein synthesis
      inhibitor cycloheximide; this protective effect was not reversed by a glutathione
      synthesis inhibitor, buthionine sulfoximine. Interestingly, the glial cell death
      induced by 1 microM staurosporine was markedly potentiated by cycloheximide.
      Staurosporine-induced neuronal death was not accompanied by an increase in
      intracellular free Ca2+ and was attenuated by 30 mM K+; this protective effect of
      high K+ was blocked by nimodipine or Co2+. Present data suggest that
      staurosporine can induce apoptosis in cultured cortical neurons and that this
      apoptosis can be blocked by raising intracellular Ca2+ or by blocking protein
      synthesis. Staurosporine exposure may be useful as a model for studying central
      neuronal apoptosis in vitro.

PMID- 7589329
TI  - Vasoactive intestinal peptide efferent projections of the suprachiasmatic nucleus
      in anterior hypothalamic transplants: correlation with functional restoration of
      circadian behavior.
AB  - Circadian rhythmicity can be restored by transplantation of fetal anterior
      hypothalamic (AH) tissue containing the suprachiasmatic nucleus (SCN) into hosts
      rendered arrhythmic by SCN ablation. However, the nature of the SCN effector
      pathways mediating functional recovery has remained elusive. To examine implant
      derived SCN innervation of the host, AH homografts (hamster-to-hamster) and
      heterografts (mouse- or rat-to-hamster) were employed and the distribution of
      vasoactive intestinal peptide (VIP) within the SCN terminal fields was evaluated.
      A comparison was made between cases where circadian locomotor activity was
      restored and cases where circadian rhythmicity remained disrupted following AH
      transplantation. A dense aggregation of VIP neurons and processes was identified
      in each transplant that restored behavioral rhythmicity in the host. In these
      cases, SCN-derived VIP fibers were integrated with the host brain and could be
      identified in host terminal fields typically innervated by SCN-VIP fibers. A
      correlation was noted between VIP innervation of the host paraventricular
      thalamic nucleus (PVT) and restoration of circadian rhythmicity. Neither
      qualitative nor quantitative differences in transplant VIP projections were noted
      between AH homografts and heterografts. These results demonstrate that SCN VIP
      neurons in AH transplants send an appropriately restricted set of efferent
      projections to the host brain and suggest that SCN efferent projections to the
      PVT may participate in mediating the functional recovery of circadian locomotor
      activity.

PMID- 7589331
TI  - Clusterin (apoJ) alters the aggregation of amyloid beta-peptide (A beta 1-42) and
      forms slowly sedimenting A beta complexes that cause oxidative stress.
AB  - Clusterin (apoJ), a multifunctional apolipoprotein made by cells in the brain and
      many other locations, is associated with aggregated amyloid beta-peptide (A beta)
      in senile and diffuse plaques of Alzheimer's disease (AD). We observed that
      purified human serum clusterin partially blocked the aggregation of synthetic A
      beta 1-42, as shown by centrifugal assays (14,000g x 10 min) and by atomic force
      (scanning probe) microscopy. Slowly sedimenting A beta complexes were formed in
      the presence of clusterin, which included aggregates > 200 kDa that resist
      dissociation by low concentrations of SDS. Clusterin enhanced the oxidative
      stress caused by A beta, as assayed by oxidative stress in PC12 cells with MTT,
      which is widely used to estimate neurotoxicity. These indications of enhanced
      neurotoxicity by the MTT assay were observed in the highly aggregated rapidly
      sedimenting fraction, but also in more slowly sedimenting "soluble" forms. This
      novel activity of slowly sedimenting A beta may enhance the neurotoxicity of A
      beta deposits in AD brains, because soluble complexes have a potential for
      diffusing to damage distal neurons.

PMID- 7589332
TI  - Injury-induced proteoglycans inhibit the potential for laminin-mediated axon
      growth on astrocytic scars.
AB  - Following injury to the adult CNS, the expression of a number of extracellular
      matrix molecules increases in regions of reactive gliosis. This glial matrix
      includes certain chondroitin sulfate proteoglycans (CS-PGs) which have been
      correlated with an inhibition of axon outgrowth. In order to test the influence
      of glial associated CS-PGs on neurite elongation directly, we sought to determine
      whether enzymatic modification of injury-induced CS-PGs could enhance neurite
      outgrowth across the surface of intact glial scars formed in vivo after
      implanting nitrocellulose filters into the cortex of adult rats. This gliotic
      tissue was subsequently explanted in vitro and used as a substrate for growing
      embryonic retinal neurons. Treatment of adult explants with chondroitinase ABC
      led to a significant increase in mean neurite length over the scar surface.
      Heparitinase treatment caused a much smaller, although significant, increase in
      neurite outgrowth. This suggested that more than one type of PG was present or
      that a single PG with both CS and HS side chains was upregulated. Western
      analysis revealed that a PG(s) with a core protein between 180 and 400 kDa was
      found to be relatively more abundant in areas of reactive gliosis induced to form
      in adult rather than neonatal animals. Simultaneous treatment of adult glial
      scars with chondroitinase and antibodies to the beta 1, beta 2 chain of laminin
      partially reversed the growth-enhancing effect of enzymatic digestion alone.
      These data demonstrate that the increase in neurite outgrowth along the surface
      of reactive astrocytes following enzymatic modification of injury-induced PGs was
      due, in part, to the presence of laminin. Thus, in this model of gliosis,
      particular PGs may act as inhibitors of neurite outgrowth by attenuating the
      potential for axon elongation that could occur due to the concomitant expression
      of growth-promoting molecules in regions of reactive gliosis.

PMID- 7589334
TI  - Elevated cathepsin D expression in kainate-evoked rat brain neurodegeneration.
AB  - Expression patterns of cathepsin D (lysosomal aspartic protease) and glial
      fibrillary acidic protein (GFAP, a marker of reactive astroglia) were determined
      by Northern blot analysis and immunohistochemistry in the rat brain during
      neurodegeneration accompanying kainate-evoked seizures. The level of cathepsin D
      mRNA in the hippocampus, limbic cortex, and temporo-parieto-occipital neocortex
      was shown to increase, starting at 6 h after kainate treatment, and reaching peak
      values at 3-7 days after the neurotoxin administration. A similar time course of
      elevated accumulation was noted for GFAP mRNA in these structures.
      Immunohistochemical analysis performed 3 days after kainate treatment showed that
      the increased cathepsin D levels were confined mainly to the degenerating neurons
      in the susceptible brain areas, while the elevated GFAP immunoreactivity was
      observed in reactive astrocytes. Although cathepsin D and GFAP expression levels
      were elevated by kainate administration, their expression patterns revealed
      significant differences with regard to both intensity and site of induction.

PMID- 7589333
TI  - Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+
      neurotoxicity in cultures of fetal rat dopaminergic neurons.
AB  - To investigate the relationships between the central nervous system and
      interleukins, ventral mesencephalic cells from embryonic 17-day-old rats were
      cultured for 3 days in vitro (DIV) and exposed to interleukin-1 beta (IL-1 beta),
      interleukin-3 (IL-3), or interleukin-6 (IL-6) for the following 2 or 3 DIV with
      or without 2 microM 1-methyl-4-phenylpyridinium (MPP+). Thus, the survival of and
      the MPP+ neurotoxicity against the dopaminergic neurons immunostained with anti
      tyrosine hydroxylase antibody were examined. For the survival studies, IL-1 beta
      has been shown to have a survival-promoting effect on dopaminergic neurons. This
      effect is initiated at a concentration between 0.1 and 1 ng/ml. In contrast to
      the effect of IL-1 beta, IL-3 and IL-6 failed to increase the survival of
      dopaminergic neurons. In MPP+ neurotoxicity analysis, only IL-6 among the three
      interleukins studied here has been shown to attenuate the MPP+ neurotoxicity
      against dopaminergic neurons in a dose-dependent manner; this neuro-protective
      action is apparent at a concentration of 10 ng/ml. In addition, these three
      interleukins did not promote glial proliferation. These findings suggest that the
      effects of IL-1 beta and IL-6 on dopaminergic neurons are not mediated by glial
      proliferation, that IL-1 beta acts as a neurotrophic factor on dopaminergic
      neurons, and that IL-6 is capable of protecting dopaminergic neurons from the
      neurotoxicity of MPP+.

PMID- 7589335
TI  - Dynamic assessment of intraspinal neural graft survival using magnetic resonance
      imaging.
AB  - Although previous work has demonstrated the usefulness of magnetic resonance
      imaging (MRI) for visualizing intraspinal transplants in vivo, the degree to
      which MRI can differentiate viable fetal neural tissue from evolving spinal cord
      pathology has not been investigated. Thus, the present study assessed whether MRI
      performed at earlier postgrafting intervals (0-20 weeks) could document the
      survival of fetal neural transplants in the injured cat spinal cord. Twelve adult
      female cats received a hemisection injury at the L1 level, followed immediately
      by implantation of either embryonic cat spinal cord or neocortex into the cavity.
      The spinal cords of three control animals were hemisected but received no
      transplant. Each animal was subsequently imaged at 4 and 8 weeks postoperative.
      Selected animals from each group were also studied at additional time points
      ranging from immediately postoperative to 20 weeks. Multislice T2-weighted and
      intermediate T1-weighted spin-echo images of the lesion or graft site were
      obtained. Correlative postmortem histological analyses revealed viable donor
      tissue in 6 of 12 transplant recipients. Spinal cords from the remaining hosts
      and the control animals all contained cysts at the surgical site that were devoid
      of donor neural tissue. The graft sites with viable tissue tended to exhibit a
      slightly hyperintense signal on both intermediate T1-weighted (T1WI) and T2
      weighted images (T2WI) throughout the entire experiment. Control cats and cats
      with failed transplants also were slightly bright on T1WI, but were very
      hyperintense on T2WI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589336
TI  - Regulation of brain-derived neurotrophic factor gene expression after transient
      middle cerebral artery occlusion with and without brain damage.
AB  - Levels of mRNA for c-fos, nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF), neurotrophin-3 (NT-3), TrkB, and TrkC were studied using in situ
      hybridization in the rat brain at different reperfusion times after unilateral
      middle cerebral artery occlusion (MCAO). Short-term (15 min) MCAO, which does not
      cause neuronal death, induced elevated BDNF mRNA expression confined to
      ipsilateral frontal and cingulate cortices outside the ischemic area. With a
      longer duration of MCAO (2 h), which leads to cortical infarction, the increase
      was more marked and elevated BDNF mRNA levels were also detected bilaterally in
      dentate granule cells and CA1 and CA3 pyramidal neurons. Maximum expression was
      found after 2 h of reperfusion. At 24 h BDNF mRNA expression had returned to
      control values. In the ischemic core of the parietal cortex only scattered
      neurons were expressing high levels of BDNF mRNA after 15 min and 2 h of MCAO.
      Analysis of different BDNF transcripts showed that MCAO induced a marked increase
      of exon III mRNA but only small increases of exon I and II mRNAs in cortex and
      hippocampus. In contrast to BDNF mRNA, elevated expression of c-fos mRNA was
      observed in the entire ipsilateral cerebral cortex, including the ischemic core,
      after both 15 min and 2 h of MCAO. Two hours of MCAO also induced transient,
      bilateral increases of NGF and TrkB mRNA levels and a decrease of NT-3 mRNA
      expression, confined to dentate granule cells. The upregulation of BDNF mRNA
      expression in cortical neurons after MCAO is probably triggered by glutamate
      through a spreading depression-like mechanism. The lack of response of the BDNF
      gene in the ischemic core may be due to suppression of signal transduction or
      transcription factor synthesis caused by the ischemia. The observed pattern of
      gene expression after MCAO agrees well with a neuroprotective role of BDNF in
      cortical neurons. However, elevated levels of NGF and BDNF protein could also
      increase synaptic efficacy in the postischemic phase, which may promote
      epileptogenesis.

PMID- 7589337
TI  - Presenting features, natural history, and prognostic factors in localized non
      Hodgkin's lymphomas: analysis of 117 cases from a single institution.
AB  - Clinical features and prognostic factors were analyzed in a series of 117
      patients with localized non-Hodgkin's lymphoma (stage I-II). Median age of the
      patients was 53 years and 52% were men; 22% had a lymphoma of low-grade histology
      and one-third presented with extranodal involvement. Eighty percent of the
      patients achieved a complete response (CR); stage of disease and histology were
      revealed as the most important factors for response. When analysis was restricted
      to intermediate/high-grade cases, stage showed a predictive value for response.
      With a median follow-up of 4.5 years, median overall survival was 12.0 years,
      with 73% and 62.5% of patients being alive at 5 and 10 years, respectively. Main
      initial parameters significantly related to a shorter survival were
      intermediate/high-grade histology, stage II, poor performance status, bulky
      disease, high serum LDH levels, increased ESR, and advanced International Index.
      In the multivariate analysis, stage, histology and performance status (PS) were
      statistically significant. Among intermediate/high-grade lymphoma patients, stage
      and PS provided prognostic value for survival. Twenty-six patients relapsed after
      CR; median survival after relapse was 2.7 years. Stage (I vs II) was the only
      predictive variable for relapse in both the whole series and the
      intermediate/high-grade subset.

PMID- 7589338
TI  - Ifosfamide, mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity
      in non-Hodgkin's lymphoma.
AB  - Patients with non-Hodgkin's lymphoma (NHL) who fail to respond to first-line
      treatment or relapse after having shown complete or partial remission have a poor
      prognosis, especially in high-grade NHL. Several salvage regimens show
      considerable toxicity and a poor long-term outcome. In this retrospective study
      we analyzed data of 55 patients (34 men and 21 women) with a median age of 66
      years (range: 18-89). The combination chemotherapy (VIM) consisted of VP-16
      (etoposide) 65 mg/m2, ifosfamide 650 mg/m2 and mitoxantrone 3 mg/m2 and was
      administered on 3 consecutive days along with mesna as uroprotection. Patients
      were treated for refractory disease or relapse and did not qualify for high-dose
      chemotherapy and ABMT. Stages according to the An Arbor classification were:
      stage I/16, II/4, III/8 and IV/37 patients. Thirty-three patients suffered from
      high-grade and 22 from low-grade NHL. Toxicity (WHO recommendations) was very
      mild. High-grade NHL showed a better response rate (18/33, 46%) than low-grade
      NHL (7/22, 36%). Overall response was 41% (12 CR and 11 PR) with a median
      duration of 36 months (range: 6-57 months). The combination therapy investigated
      exhibits mild toxicity even in extensively pretreated or elderly patients. The
      overall response rate of 41% might be improved by increased dosage and growth
      factor support.

PMID- 7589339
TI  - The effect of mast cell growth factor on peripheral blood granulocyte-macrophage
      colony-forming cells in methylcellulose in myeloproliferative disorders.
AB  - Clonogenic cell culture assay was used to evaluate the effect of mast cell growth
      factor (MGF) on peripheral blood granulocyte-macrophage (GM) progenitors in 26
      patients with myeloproliferative disorders (MPDs). MGF alone had a statistically
      significant stimulatory effect on GM colony formation, as also did interleukin-3
      (IL-3) and GM colony-stimulating factor (GM-CSF), although the progenitors could
      form colonies spontaneously as well. When MGF was combined with either IL-3 or GM
      CSF the effect was additive and was as great as that achieved with a mixture of
      IL-3, GM-CSF, G-CSF and IL-6. The highest colony-forming capacity of all was seen
      when MGF was added to the above mixture. Within the subgroups of MPDs, the
      stimulatory effect of MGF was significant in polycythemia vera (PV), essential
      thrombocythosis (ET) and chronic myelogenous leukemia (CML). MGF was the most
      potent single factor in PV, while GM-CSF was most effective in idiopathic
      myelofibrosis and both IL-3 and GM-CSF in CML. The fact that the ability of MGF
      to induce colony growth varied between the subgroups of MPDs may mean that the
      target progenitors in these diseases are biologically different. In conclusion,
      MGF, either alone or with others, was a potent growth factor for GM progenitors
      in MPDs.

PMID- 7589340
TI  - Treatment of 34 patients with myelodysplastic syndromes with 13-CIS retinoic
      acid.
AB  - Thirty-four patients with myelodysplastic syndromes, 23 men and 11 women, aged
      between 47 and 80 years, with all types of myelodysplastic syndromes were treated
      with 13-cis-retinoic acid. The dose of retinoic acid ranged between 10 and 60
      mg/m2/daily and was administered in combination with vitamin E to diminish side
      effects. The duration of treatment was 3 months to 5 years. Partial remission was
      achieved in 4 patients, 1 with RA type, 2 with RAEB and 1 with CMML. Survival
      ranged from 1 to 5 years. Patients who received retinoic acid developed mild side
      effects. In conclusion, the administration of 13-cis-retinoic acid improves the
      hematological picture in a small number of MDS patients (11.7%).

PMID- 7589341
TI  - Virus-associated haemophagocytic syndrome in previously healthy adults.
AB  - The clinical characteristics of 15 adult patients with virus-associated
      haemophagocytic syndrome (VAHS) were studied. The patients were 3 males and 12
      females with a mean age of 39.5 years (range 20 to 67 years). Seven patients
      (mean age 48.6 years) were immunosuppressed by drugs or as a result of having
      malignant or autoimmune disease. Eight patients (mean age 31.6 years) had no
      underlying diseases. The prognosis of the patients with immunosuppression was
      poor, as previously reported, and 3 of them died. In younger adult patients with
      this syndrome who had no underlying immunosuppressive diseases, the prognosis was
      good even without therapy. The sera from the patients in both groups contained
      extremely high levels of macrophage colony-stimulating factor (M-CSF) and
      slightly elevated levels of tumour necrosis factor-alpha (TNF-alpha). These
      findings suggested that VAHS, can occur in presumably healthy adults and that
      VAHS can be a more benign condition than previously believed. M-CSF and TNF-alpha
      may play an important role in the development of the syndrome in both groups.

PMID- 7589342
TI  - HIV-related non-Hodgkin's lymphoma among European AIDS patients. AIDS in Europe
      Study Group. AIDS in Europe Study Group.
AB  - The epidemiology of HIV associated non-Hodgkin's lymphoma (NHL) was investigated
      in 6550 European patients with AIDS. NHL was diagnosed in 3.5% of all patients at
      the time of the AIDS diagnosis. Although the probability of being diagnosed with
      NHL at AIDS diagnosis was significantly higher among intravenous drug users than
      among homosexual men, and was associated with increasing age, the observed
      incidences of NHL were more strikingly similar than any differences. The rate of
      developing NHL after a previous AIDS diagnosis was 2.4 per 100 patient years of
      follow-up, and remained constant during a 5-year follow-up period. While primary
      brain lymphomas comprised only 9% of NHL diagnosed at the time of AIDS, they
      comprised 38% of NHL diagnosed after AIDS (p < 0.001). The prognosis for patients
      with NHL at AIDS diagnosis was poor with a median survival of 5 months. A
      diagnosis of primary brain lymphoma was uniformly associated with a poor outcome.
      It is concluded that the probability of developing NHL in late stage HIV
      infection is lower than previously anticipated from the results of small studies
      on patients receiving long-term anti-retroviral therapy.

PMID- 7589343
TI  - Blunted erythropoietin response to anaemia in tuberculosis.
AB  - The precise cause of the anaemia that is commonly associated with severe
      pulmonary tuberculosis (PTB) has not been elucidated. The role of erythropoietin
      (Epo), the central hormone regulating red cell formation, still awaits
      clarification. We therefore determined serum Epo levels in patients with PTB;
      group 1, haemoglobin less than 110 g/L, group 2, haemoglobin greater than 110
      g/L; group 3, controls, consisted of matched individuals with uncomplicated iron
      deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained
      from patients with PTB and the controls, cultured, and the supernatant fluid
      (SNF) harvested. Tumour necrosis factor alpha (TNF alpha) levels were determined
      in the SNF, which were then added in various dilutions to a hepatocellular
      carcinoma cell line (HepG2) capable of regulated EPO synthesis in vitro. The
      influence of this cytokine was defined by the addition of specific neutralising
      anti-TNF alpha antibodies in this assay system. Patients in group 1 had
      significantly lower Epo levels (54 + 11 mU/mL) compared with those in group 3
      (142 +/- 41 mU/mL) (p < 0.01). Monocyte supernatants from patients in the anaemic
      PTB group had markedly elevated TNF alpha levels and significantly suppressed Epo
      output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently
      abrogated by anti-TNF alpha antibodies. Serum Epo levels were inappropriately low
      in untreated PTB patients when compared with corresponding haemoglobin levels in
      iron deficient controls. This blunted response could be ascribed to release of
      TNF alpha or other cytokines by activated monocytes.

PMID- 7589344
TI  - Persistent growth impairment of bone marrow stroma after antilymphocyte globulin
      treatment for severe aplastic anaemia and its association with relapse.
AB  - Bone marrow from 65 patients with aplastic anaemia (AA) was tested for stroma
      growth in short term cultures (2 weeks) and for colony formation by haemopoietic
      precursor cells during the course of their disease. In 18 untreated patients,
      mean stroma growth was 30% of normal and colony formation was virtually absent.
      After treatment with immunosuppression (IS), as estimated from 90 examinations in
      54 patients, stroma growth was approximately 50% and colony growth approximately
      10% of normal. Growth impairment of stroma and haemopoietic precursors persisted
      for 10 and more years after IS. Results of 2-week stroma cultures were compared
      with results of long term bone marrow cultures in 10 AA patients and 4 controls.
      At 2 weeks, growth of aplastic marrow was delayed compared to normal, but this
      difference became less evident with prolonged incubation time. In vitro growth
      abnormalities were compared with the clinical evolution after IS. The development
      of late haematological complications (paroxysmal nocturnal haemoglobinuria (PNH))
      and myelodysplastic syndrome (MDS), did not correlate with the degree of stroma
      growth impairment. However, relapse of aplasia was associated with poor stroma
      growth: 8/29 patients with stroma confluence of < or = 30% during haematological
      remission versus 1/25 with stroma confluence of > 30% relapsed. We conclude that
      (i) the haematopoietic microenvironment is frequently coinvolved in the disease
      process of AA, (ii) a defect is detected in short term rather than in long term
      stroma cultures and, (iii) relapse is more frequent in patients with poor stroma
      growth.

PMID- 7589345
TI  - FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low
      grade non-Hodgkin's lymphoma.
AB  - Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with promising
      therapeutic activity in the lymphoproliferative disorders and in particular in
      low-grade non-Hodgkin's lymphoma (LG-NHL). In order to evaluate FLU in
      combination with other antineoplastic agents, we used a three-drug combination of
      FLU, mitoxantrone and prednisone (FMP) to treat 18 patients with recurrent LG
      NHL. The FMP regimen was as follows: FLU, 25 mg/m2 i.v. on days 1 to 3;
      mitoxantrone, 10 mg/m2 i.v. on day 1; prednisone 40 mg i.v. on days 1 to 5. Of
      the 18 patients, 4 (22%) achieved complete response (CR), 9 (50%) partial
      response, and the remaining 5 showed no benefit from the treatment. The 4 CR
      patients are still in remission after 4, 6, 6, and 8 months, respectively. The
      median duration of overall survival of all patients was 9 months. The major toxic
      effects observed were neutropenia (50%) and infections and/or febrile episodes
      (17%); no fatalities due to drug side effects occurred. These results confirm the
      efficacy of the fludarabine-mitoxantrone combination-containing regimen in
      inducting a good remission rate with moderate side effects in recurrent LG-NHL.

PMID- 7589346
TI  - Methicillin-resistant Staphylococcus aureus: colonization and development of
      infection in patients with haematological disorders.
AB  - A retrospective study of 53 patients with haematological disorders whose
      bacterial cultures were positive for methicillin-resistant Staphylococcus aureus
      (MRSA), was performed to analyse the risk factors for MRSA infection, and the
      prognostic factors. Sixteen patients showed colonization by MRSA but never
      developed infection(C), 16 showed colonization and subsequent infection(C-I),
      while 21 had MRSA infection at the time of first culture (I). Poor performance
      status, thrombocytopenia, increased serum urea nitrogen and decreased serum
      cholinesterase were more prominent in (I) than (C) + (C-I). The risk factors
      associated with the development of infection from colonization were age and serum
      cholinesterase. In addition, lower respiratory tract infection as a type of
      infection, non-remission status of the haematological malignancy and an
      inappropriate antibiotic therapy were associated with a poor prognosis for MRSA
      infection.

PMID- 7589347
TI  - Erythropoietin concentration in the serum from patients with primary
      thrombocythaemia.

PMID- 7589348
TI  - Cardiac tamponade: the first manifestation of a generalized lymphoma in a patient
      with HIV infection.

PMID- 7589349
TI  - Hypercalcaemia caused by all-trans retinoic acid (ATRA) treatment in a case of
      acute promyelocytic leukaemia was manageable after decreasing the ATRA dose to 27
      mg/m2/day.

PMID- 7589350
TI  - Treating the anaemia of a pregnancy with heterozygous beta thalassaemia with
      recombinant human erythropoietin (r-HuEPO)

PMID- 7589351
TI  - Inherited phosphofructokinase deficiency associated with hemolysis and exertional
      myopathy.

PMID- 7589352
TI  - Possible role of T-cell surface molecule gene expression in the mixed lymphocyte
      culture for predicting transplantation-related complications after allogeneic
      bone marrow transplantation.

PMID- 7589353
TI  - Recombinant human erythropoietin at high doses stimulates thrombopoiesis:
      treatment for protracted severe myelosuppression complicating interferon-alpha
      and busulfan therapy for chronic myelogenous leukaemia.

PMID- 7589354
TI  - Acceptability of medical abortion in early pregnancy.
AB  - A review of 12 published studies on patient attitudes and reactions to early
      first-trimester pregnancy termination by medical methods shows consistent
      patterns, despite important differences in study design, measurement and outcome.
      In most trials that offered participants a choice between surgical and medical
      abortion, 60-70% of patients chose the medical method. The most common reasons
      cited for choosing the medical method were greater privacy and autonomy, less
      invasiveness and greater naturalness than surgery. Frequently mentioned drawbacks
      included pain, the duration of bleeding, the number of visits, and the waiting
      time to know if the treatment has been successful. Most women who had a medical
      abortion said they were satisfied with the method, would recommend it to friends
      and would use it again if they needed another abortion.

PMID- 7589355
TI  - Knowledge and perceptions of emergency contraceptive pills among a college-age
      population: a qualitative approach.
AB  - Results from focus-group discussions with a population of university students who
      have convenient access to emergency contraceptive pills show that basic awareness
      about this method is high, although specific knowledge on appropriate use, such
      as the time limit for use, the level of effectiveness and the possible side
      effects, is lacking. Approval of the method is widespread among both female and
      male students, although students did voice anxieties about irresponsible use and
      the lack of protection against the human immunodeficiency virus and other
      sexually transmitted diseases. Many of their concerns stem from incomplete
      information about how the regimen works. Students noted how rarely emergency
      contraceptive pills are discussed, and were curious to know more. They asked for
      routine education on the method, as well as more general discussion.

PMID- 7589356
TI  - Short-term acceptability of the female condom among staff and patients at a New
      York City Hospital.
AB  - An acceptability study of the female condom undertaken at New York's Harlem
      Hospital between August 1993 and February 1994 enrolled 52 women aged 18-57, 41
      of whom (79%) used the female condom at least once. Of these, one-half used the
      female condom at least three times and 40% used it once; on average, women used
      it 2.4 times. Two-thirds of users liked the female condom either very much or
      somewhat, 20% were neutral and 15% stated that they did not like it. One-half of
      the women reported that their partner liked the device, while 17% said he felt
      neutral about it and approximately one-quarter said he disliked it. Seventy-three
      percent of respondents and 44% of their partners preferred the female condom to
      the male condom.

PMID- 7589357
TI  - How old are U.S. fathers?
AB  - One in every six U.S. birth certificates have no information on the age of the
      baby's father; for more than four in 10 babies born to adolescent women, no data
      are available on the father's age. Information from mothers aged 15-49 who had
      babies in 1988 and were surveyed in the National Maternal and Infant Health
      Survey indicates that fathers for whom age is not reported on the birth
      certificate are considerably younger than other fathers. In 1988, 5% of fathers
      were under age 20, and 20% were aged 20-24. Fathers typically are older than
      mothers, especially when the mothers are teenagers. Fathers who are unmarried,
      black or partners of lower income women are younger than other fathers.

PMID- 7589358
TI  - Repeat abortion and use of primary care health services.
AB  - One-third (34%) of 2,001 women who sought an abortion in 1991-1992 in Wichita,
      Kansas, were repeat-abortion patients. Compared with first-time abortion
      patients, repeat-abortion patients were significantly older, more often black,
      and younger at their first pregnancy (p < .001). The two groups did not vary
      significantly by income or age at first intercourse. However, repeat-abortion
      patients were significantly more likely than first-time patients to have been
      using a contraceptive method at the time of conception (65% compared with 59%)
      and more likely to say they always or almost always used a method (63% and 53%,
      respectively). More than 40% of women in each group reported they had no personal
      physician. Further, 34% of repeat-abortion patients said they had no follow-up
      examination after their previous abortion, and 28% said they received no
      contraceptive counseling. Only half of women whose pregnancy was confirmed by
      their personal physician obtained an abortion referral from that physician.

PMID- 7589361
TI  - The implant vs. the injectable.

PMID- 7589360
TI  - Bringing the fundamentals of gender studies into safer-sex education.

PMID- 7589359
TI  - The 'family cap': a popular but unproven method of welfare reform.

PMID- 7589362
TI  - Intravaginal barriers: reliable protection against pregnancy and STDs?

PMID- 7589365
TI  - Bronchiolitis obliterans organizing pneumonia in an AIDS patient.
AB  - We present a case of bronchiolitis obliterans organizing pneumonia in a patient
      with acquired immune deficiency syndrome. Only three cases have previously been
      reported in patients infected with human immunodeficiency virus. In these four
      cases, bronchiolitis obliterans organizing pneumonia was similar in presentation,
      radiographic features and clinical course to that occurring in patients not
      infected with human immunodeficiency virus.

PMID- 7589363
TI  - Pulmonary studies using positron emission tomography.
AB  - The detailed investigation of regional differences in lung function at a local
      level began when suitable gamma-ray emitting isotopes and focused external
      radiation detectors (especially the Anger gamma-camera) became available. A major
      recent advance has been the development of positron emission tomography (PET),
      which provides a powerful combination of highly accurate tomographic
      reconstruction of radioisotope concentration with a potentially unlimited list of
      biological compounds to be labelled with the positron emitting isotopes of
      oxygen, carbon and fluorine. Early studies using PET focused on the inhalation of
      11CO (or C15O) and 19Ne gases and the intravenous injection of 13N in saline and
      H215O for the measurement of relatively simple aspects of regional lung function,
      such as tissue, blood and gas volumes, blood flow, ventilation and
      ventilation/perfusion (V'A/Q'). More recent work has been directed towards the
      more challenging areas of regional endothelial permeability, carbohydrate
      utilization, enzyme and receptor binding assays, and in vivo pharmacokinetics.
      The short physical half-lives of the isotopes (17 s to 2 h) and the noninvasive
      nature of PET allows serial measurements to be made on patients (within the
      constraints of permitted radiation doses) to assess the effect of physiological
      and therapeutic interventions.

PMID- 7589366
TI  - Pleural amyloidosis: thoracoscopic aspects.
AB  - We describe the case of a 60 year old man with primary amyloidosis, who suffered
      from peripheral neuropathy and cardiomyopathy and who presented with recurrent
      right pleural effusion. For this reason, he was admitted to hospital for
      thoracoscopic examination with pleurodesis. Macroscopic examination of the
      parietal pleura revealed a diffuse inflammation and light brown deposits that
      where covered with nodules. Biopsy specimens confirmed the amyloid deposition.
      This macroscopic appearance is described for the first time, and suggests that a
      local pleural synthesis of amyloid substance may occur during the course of
      systemic amyloidosis.

PMID- 7589364
TI  - Bronchiolitis obliterans organizing pneumonia associated with minocycline
      therapy: a possible cause.
AB  - We report the case of a woman who presented with dyspnoea whilst taking
      minocycline for acne. Imaging features of bilateral patchy alveolar opacities
      suggested a diagnosis of bronchiolitis obliterans organizing pneumonia, which was
      confirmed by lung biopsy. The patient improved, partially, after stopping
      minocycline, and then completely on treatment with corticosteroids, without
      relapse when these where stopped 8 weeks later.

PMID- 7589369
TI  - Respiratory function measurements in infants: symbols, abbreviations and units.

PMID- 7589367
TI  - Giant bilateral fibrous dysplasia of first ribs: compression of mediastinum and
      thoracic outlet.
AB  - A 43 year old woman presented with two large bilateral tumours of the first ribs
      that compressed the right subclavian vessels, trachea and oesophagus and led to
      right arm oedema, severe dyspnoea and dysphagia. The resected tumours showed
      typical histological features of fibrous dysplasia without malignant
      transformation. The right tumour weighed 1.5 kg and measured 17 x 13 x 10 cm.
      This report demonstrates that major surgery is still possible for resection of
      such exceptional giant compressive lesions, since fibrous dysplasia is a benign
      and non-infiltrative tumour.

PMID- 7589371
TI  - Drug-resistant pulmonary tuberculosis.

PMID- 7589370
TI  - Respiratory function measurements in infants: measurement conditions. Working
      Group of the European Respiratory Society and the American Thoracic Society.

PMID- 7589368
TI  - Short-term effects of air pollution on health: a European approach using
      epidemiological time-series data. The APHEA project: background, objectives,
      design.
AB  - Recent studies investigating the adverse health effects of air pollution indicate
      that effects exist around and below the current national and international air
      quality guidelines and standards. However, the difficult methodological issues
      involved, and the diversity of analytical techniques so far applied, hinder
      direct between-study comparability and the drawing of clear conclusions. The
      APHEA (Air Pollution on Health: European Approach) project is an attempt to
      provide quantitative estimates of the short-term health effects of air pollution,
      using an extensive data base from 10 different European countries, which
      represent various social, environmental and air pollution situations. Within the
      framework of the project, the methodology of analysing epidemiological time
      series data, as well as that of performing meta-analysis, are further developed
      and standardized. Data have been collected from 15 European cities with a total
      population exceeding 25 million. The exposure data consist of daily measurements
      of black smoke, sulphur dioxide, suspended particles, nitrogen dioxide and ozone
      (each available in several, though not all, cities) from already existing
      monitoring networks. There is substantial variability in air pollution mixtures
      and air pollutant levels in participating cities. The mean (24 h) levels of SO2
      range 27-327 micrograms.m-3 in the winter season, and those of black smoke range
      15-292 micrograms.m-3. The mean (1 h) levels of ozone in the summer season range
      32-166 micrograms.m-3. The outcome data are daily counts of total and cause
      specific deaths and hospital emergency admissions. Data on potential confounders
      (mainly meteorological and chronological variables) are also used. There is large
      diversity in the climatic conditions in the different cities.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7589372
TI  - Respiratory effects of air pollution: the importance of a multidisciplinary
      approach to conduct research.

PMID- 7589373
TI  - Quality of life measurement in asthma.

PMID- 7589375
TI  - The psychological factors associated with poor compliance with treatment in
      asthma.
AB  - Poor patient compliance with inhaled medication is known to cause morbidity and
      mortality in asthma. The reasons for nonadherence are not fully understood. We
      wondered whether psychological factors, such as patient attitudes to asthma and
      its treatment, anxiety, depression, and interpersonal problems, may be related to
      asthma self-care and compliance. In a prospective study, 102 patients with
      asthma, aged 18-70 yrs, requiring treatment with regular inhaled corticosteroids
      and beta-agonists were recruited from a hospital out-patient clinic and four
      general practices in South East London. They underwent psychological assessment
      using the Hospital Anxiety and Depression Scale (HADS), the Inventory of
      Interpersonal Problems (IIP), and a semi-structured interview focusing on patient
      attitudes, self-care, compliance, social support and treatment beliefs. Patients
      were given terbutaline and budesonide turbohalers to use twice daily over 12
      weeks. Turbohaler Inhalation Computers (TICs) recorded each inhalation, providing
      a measurement of compliance. Seventy two patients completed the study. Thirty
      seven took less than 70% of the prescribed dose over the study period or omitted
      doses for 1 week and were defined as noncompliant. The noncompliant group had a
      higher mean (SD) score for depression (4.7 (3.3)) than the compliant group (3.2
      (2.5)). The sample had a high mean (SD) score for anxiety (8.3 (4.4)), but there
      was no significant difference between the compliant and noncompliant groups.
      Patients' self-report and clinicians' impressions of compliance were not good
      predictors of actual compliance. Using discriminant analysis, a model was
      obtained from the questionnaires and interview items, which correctly classified
      74% of the patients as compliant or non-compliant.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7589374
TI  - Comparison of performance of four instruments in evaluating the effects of
      salmeterol on asthma quality of life.
AB  - Quality of life measures are increasingly used as important efficacy endpoints in
      studies of drugs for asthma. The purpose of this study was to assess both the
      sensitivity to change and the construct validity of four different quality of
      life instruments in patients with asthma. In a double-blind, parallel group
      study, 120 moderate asthma patients, aged between 18-70 yrs, received either
      inhaled salmeterol 50 micrograms b.i.d. or inhaled salbutamol 400 micrograms
      b.i.d. In addition to respiratory outcomes, quality of life was measured at a 6
      weeks follow-up using: 1) Asthma Quality of Life Questionnaire (AQLQ); 2) Living
      With Asthma Questionnaire (LWAQ); 3) Sickness Impact Profile (SIP); 4) Rating
      Scale (RS); and Standard Gamble (SG) utilities. Salmeterol led to significant
      improvements over salbutamol on virtually all clinical outcomes. Although all the
      quality of life instruments showed the same trend in favour of salmeterol, only
      the AQLQ and RS utilities showed significantly greater improvement on salmeterol
      than on salbutamol. Except for the AQLQ, the correlation between change in lung
      function and change in quality of life was generally low. Whereas, the AQLQ
      correlated well with the patient's overall assessment of efficacy (r = 0.64), the
      LWAQ, SIP and utilities failed to show such a correlation. The AQLQ showed the
      best correlation with symptom scores. The cross-sectional correlation between the
      AQLQ and the LWAQ was 0.73, whereas the longitudinal correlation was only 0.29.
      The SG generally showed poor correlation with other measures, including the RS.
      In conclusion, patients given salmeterol showed a greater improvement in quality
      of life compared to patients given salbutamol. Of the disease-specific
      questionnaires the Asthma Quality of Life Questionnaire was found to be more
      responsive to change than the Living With Asthma Questionnaire and showed greater
      validity. Of the generic instruments, the rating scale utilities were most
      responsive. The Standard Gamble showed poor correlation with other measures.

PMID- 7589378
TI  - Airway and lung elastic fibre is not reduced in asthma nor in asthmatics
      following corticosteroid treatment.
AB  - By morphometric investigation of the relative content of elastic and collagen
      fibres, we have tested the hypothesis that loss of elastic fibres in the
      conducting airways and lung parenchyma may reduce tissue elastic recoil,
      resulting in increased airway maximal closure and apparent increased
      responsiveness. The study groups comprised: Group A (n = 11) with relatively mild
      atopic asthma using inhaled bronchodilators prn (i.e. short-term corticosteroids
      users); Group B (n = 9) with more severe asthma requiring inhaled bronchodilators
      regularly, and daily inhaled glucocorticosteroids (i.e. longterm corticosteroid
      users); Group C (n = 12) normal healthy workers. Bronchial biopsy samples were
      taken from three sites from the left lung. Group A biopsy samples were taken
      before and after a 4 wk treatment period with inhaled corticosteroids (200
      micrograms b.i.d.) and the relative elastic and collagen fibre content of a
      subepithelial zone was determined from electron micrographs. In a parallel study,
      the relative proportion of elastic fibre in post mortem lung tissue samples
      (inner aspect of the bronchial wall, alveolar wall, and points of attachment of
      surrounding alveoli to intrapulmonary bronchi) from subjects suffering a fatal
      asthma attack (n = 11), and non-asthmatic suffering sudden death (n = 9), were
      determined using Miller's elastic and eosin counterstain for light microscopy. In
      bronchial biopsies of normal subjects, 4.6 (SEM 1.1)% of subepithelial connective
      tissue was elastic fibre, similar to mild asthmatic subjects, 1.9 (SEM 0.48)%.
      Neither short-term (4 weeks) inhaled corticosteroid (200 micrograms b.i.d.) nor
      long-term (< 6 months) treatment with variable doses of inhaled steroids (100
      1000 micrograms b.i.d.) significantly altered the elastic or collagen content of
      the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589379
TI  - Allergen-induced late-phase airways obstruction in the pig: the role of
      endogenous cortisol.
AB  - In developing a novel model for studies of the allergen-induced late-phase
      airways obstruction, by using the pig, the importance of endogenous cortisol
      levels was examined by the use of metyrapone, a cortisol-synthesis inhibitor.
      Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen.
      One group of pigs was treated with a constant infusion of metyrapone in order to
      maintain low levels of plasma cortisol. Ascaris suum allergen was nebulized into
      the lower airways and plasma cortisol and catecholamine levels, total lung
      resistance and dynamic compliance, blood gases and pH, and blood flow in the
      bronchial circulation were continuously recorded for 8 h. At the time of allergen
      challenge, the plasma cortisol levels in sensitized pigs were 455 +/- 37 nM and
      40.1 +/- 3.8 nM in non-metyrapone-treated and metyrapone-treated pigs,
      respectively. No difference was seen between the magnitude of the acute
      bronchoconstrictor response in the two groups. A late airways obstruction,
      starting at about 4 h, developed only in pigs with low cortisol levels, whereas a
      late increase in blood flow in the bronchial circulation was seen in both groups,
      even if a late airways obstruction was absent. Plasma adrenaline did not seem to
      influence the late-phase reaction. These results suggest that endogenous cortisol
      levels, but not adrenaline, modify the late response to allergen in the pig.
      Furthermore, it is suggested that the pig is a suitable model for studies of
      allergic reactions in the airways, if metyrapone is used to keep plasma cortisol
      levels within a normal range.

PMID- 7589380
TI  - Large lungs and growth hormone: an increased alveolar number?
AB  - Previous physiological studies suggest that increased lung growth in patients
      with acromegaly is associated with either a normal or above normal pulmonary
      transfer factor. These findings can be interpreted to suggest either alveolar
      hypertrophy or hyperplasia as the mechanism for lung growth in this condition.
      Since the ventilated airspaces retain normal elastic properties, we wanted to
      determine whether the mechanism for lung growth in acromegaly is the result of an
      increased alveolar number rather than size. Measurements of pulmonary
      distensibility (K) (an index of alveolar size), elastic recoil, single-breath
      carbon monoxide transfer factor and carbon monoxide transfer coefficient (KCO),
      pulmonary capillary blood volume and alveolar membrane diffusing capacity,
      together with chest width, were compared in nonsmoking, acromegalic and normal
      men and women, with and without an increased lung size. Pulmonary transfer factor
      was normal for all groups studied, regardless of lung size. However, KCO was
      inversely related to total lung capacity (% predicted) for all subjects and KCO
      (% predicted) was inversely related to chest width in men. Pulmonary capillary
      blood volume (% predicted) was inversely related to total lung capacity (%
      predicted) for subjects with large lungs. Pulmonary distensibility (K), membrane
      diffusing capacity and elastic recoil were within the normal range. These
      findings suggest normal alveolar size, alveolar membrane surface area and
      mechanical function in subjects with large lungs. They also suggest that KCO may
      not be a reliable guide to the interpretation of the mechanism of lung growth in
      individuals with disproportionately large lungs, and may be reduced because not
      all the alveoli are perfused. The normal values for pulmonary distensibility
      found in all our individuals with large lungs, including acromegalics, suggest
      that lung growth has been achieved by an increased alveolar number rather than
      size. However, morphometric studies of the lungs of nonsmoking, acromegalic
      subjects without lung disease, are required to substantiate this finding.

PMID- 7589377
TI  - Increased maximal airway response to methacholine during seasonal allergic
      rhinitis in nonasthmatic subjects: relationships with airway wall thickness and
      inflammation.
AB  - This study was carried out to determine whether the increase in airway
      responsiveness induced by natural antigenic exposure in nonasthmatic subjects is
      associated with an increase in maximal bronchoconstrictor response (MBR), and if
      these changes could be due to an increase in airway wall thickness from allergen
      induced increase in airway inflammation. In 11 nonasthmatic subjects with
      seasonal allergic rhinitis, a methacholine challenge was obtained monthly, during
      and out of pollen exposure. Each subject had a high-resolution chest tomography
      in and out of the pollen season, to determine the relative thickness of the right
      intermediary bronchus over its total diameter (T/D), as well as inflammatory cell
      counts, apparent basement membrane thickness as an indication of subepithelial
      fibrosis and epithelial desquamation in bronchial biopsy specimens. In season,
      the mean provocative concentration of methacholine producing a 20% decrease in
      forced expiratory volume in one second (PC20) decreased from 51.5 to 25.8 mg.mL
      1, and the maximal post-methacholine fall in forced expiratory volume in one
      second (delta FEV1,max) or forced vital capacity (delta FVC) and the slope of the
      dose response curve (DRS) increased compared with out of season: delta FEV1,max
      44 +/- 5 vs 25 +/- 5%; delta FVC 34 +/- 5 vs 16 +/- 4%; and slope of DRS 14.1 +/-
      2.8 vs 6.9 +/- 1.3%/mg.mL-1. No significant change was observed in T/D ratio. The
      seasonal change in delta FVC was positively correlated with the delta FEV1,max
      (rs = 0.891) and the change in DRS (rs = 0.909), but not with the change in PC20,
      nor with changes in bronchial biopsy inflammatory features or T/D ratio.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589376
TI  - Inhaled lysine acetylsalicylate (L-ASA) attenuates the bronchoconstrictor
      response to adenosine 5'-monophosphate (AMP) in asthmatic subjects.
AB  - When administered by inhalation, adenosine 5'-monophosphate (AMP) provokes dose
      related bronchoconstriction in asthmatic subjects by a mechanism believed to
      involve mast cell mediator release. However, little is known of the change in
      airway responsiveness to AMP after cyclo-oxygenase blockade. The aim of this
      study was to investigate the effect of the potent cyclo-oxygenase inhibitor,
      lysine acetylsalicylate (L-ASA) administered by inhalation, on AMP-induced
      bronchoconstriction in a group of nine asthmatic subjects. The subjects studied
      attended the laboratory on six separate occasions to receive nebulized L-ASA
      (solution of 90 mg.ml-1) or matched placebo (glycine solution, 30 mg.ml-1) 15 min
      prior to bronchoprovocation tests with AMP, histamine and methacholine in a
      randomized, double-blind order. Changes in airway calibre were followed as forced
      expiratory volume in one second (FEV1) and agonist responsiveness was expressed
      as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20).
      Administration of both L-ASA and glycine solution caused a small but significant
      acute fall in FEV1 from baseline, which returned to normal within 15 min. When
      compared to placebo, inhaled L-ASA reduced the airway responsiveness to AMP in
      all the subjects studied, the geometric mean (range) values for PC20 AMP
      increasing significantly from 36.3 (7.9-250.5) to 101.8 (27.2-1300) mg.ml-1 after
      placebo and L-ASA, respectively. Moreover, nebulized L-ASA induced a small but
      significant reduction in airway responsiveness to histamine, the geometric mean
      (range) PC20 values for histamine increasing from 2.77 (1.05-5.49) to 4.36 (1.69
      11.24) mg.ml-1 after placebo and L-ASA, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7589381
TI  - The isolation and characterization of non-typeable Haemophilus influenzae from
      the sputum of adult cystic fibrosis patients.
AB  - The role of non-typeable Haemophilus influenzae in cystic fibrosis (CF) remains
      unclear. We wanted, therefore, to determine the presence and characteristics of
      non-typeable H. influenzae in sputum samples from patients with CF. In order to
      do this, we have assessed sputum samples from 55 consecutive clinically stable
      patients seen routinely at an adult CF out-patient clinic. Quantitative bacterial
      culture was performed using a selective media containing cefsoludin, and isolates
      were characterized by biotyping and outer membrane protein profile analysis. In
      17 (30%) of these samples, non-typeable H. influenzae was isolated and was
      present in similar viable numbers (mean 7.7 x 10(8) colony-forming units (cfu).mL
      1; SEM 3.1) to Pseudomonas aeruginosa (mean 8 x 10(8) cfu.mL-1: SEM 2.4). All non
      typeable H. influenzae isolates recovered were beta-lactamase negative and
      sensitive to a range of antibiotics. Several biotypes and outer membrane protein
      profiles were observed, with no apparent association between these two phenotypic
      characteristics. The study showed that large numbers of non-typeable H.
      influenzae are often present in sputum from adult patients with CF. Further
      longitudinal studies of outer-membrane protein profile analysis are required to
      determine the dynamics of non-typeable H. influenzae colonization in individual
      patients and the clinical significance.

PMID- 7589382
TI  - Recombinant human DNase I in cystic fibrosis patients with severe pulmonary
      disease: a short-term, double-blind study followed by six months open-label
      treatment.
AB  - Chronic pulmonary infection is the major cause of morbidity and mortality in
      cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has
      been shown to dramatically reduce the viscoelasticity of the sputum from CF
      patients. Phase II and III clinical trials have shown the drug to be safe, and
      that patients with a forced vital capacity (FVC) of > 40% predicted show an
      improvement in pulmonary function when receiving rhDNase. The current study
      evaluates the safety and efficacy of rhDNase in the most severly ill CF patients
      (FVC < 40% predicted). A double-blind, randomized, placebo-controlled trial in
      which patients received either 2.5 mg rhDNase twice daily or placebo for a period
      of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy
      patients were recruited for the double-blind study, and 64 entered the OEP of
      whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice
      daily. In both the double-blind period and the OEP the drug appeared to be safe.
      During the double-blind study, forced expiratory volume in one second (FEV1) and
      FVC improved in both groups but there was no statistically significant difference
      between the groups. In the OEP, there was mean improvement in percentage
      predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating.
      In conclusion, DNase is safe when administered in conjunction with a rigorous
      regimen of chest physiotherapy to severely ill patients (FVC < 40% predicted)
      with CF. The double-blind, 14 day study showed no significant improvement in
      pulmonary function but some patients may have improved after longer
      administration of rhDNase.

PMID- 7589383
TI  - Evolution of resting lung function in the first year after cardiac
      transplantation.
AB  - The aim of our study was to characterize the time course and magnitude of the
      changes in lung function in the first year after cardiac transplantation. Resting
      pulmonary function tests (spirometry, lung volumes and transfer factor) were
      performed in 14 patients prior to and at 1, 3 and 12 months after surgery.
      Resting central haemodynamics were also measured serially in the first year post
      transplantation. Before transplantation, patients had impaired resting lung
      function with marked decrease in transfer factor (TL,CO). Although resting
      central haemodynamics improved markedly within the first week after cardiac
      transplantation, lung function (forced expiratory volume in one second (FEV1))
      was significantly improved only at three months post-transplantation. TL,CO,
      however, decreased further early after cardiac transplantation. By 12 months,
      FEV1 and forced vital capacity had increased significantly by 31 and 33%,
      respectively, while total lung capacity increased by 22%. On the other hand,
      TL,CO did not increase significantly and remained well below normal at 12 months
      after cardiac transplantation, at a value equal to 68% of predicted. We conclude
      that the resting abnormalities in lung function of most patients with heart
      failure are reversible after cardiac transplantation, except for TL,CO which
      remains below normal values. Recovery of lung function, however, lags behind the
      improvement in cardiac function.

PMID- 7589384
TI  - The role of transbronchial needle aspiration in the diagnosis of peripheral lung
      masses or nodules.
AB  - The purpose of this study was to evaluate the role of transbronchial needle
      aspiration (TBNA) in the diagnosis of peripheral lung lesions. We attempted to
      perform TBNA in 37 patients referred to our hospital for diagnostic evaluation of
      radiographically evident peripheral masses (23 cases) or nodules (14 cases). None
      of them had bronchoscopic evidence of endobronchial lesion. The aspirations were
      performed under fluoroscopic guidance, through a fibreoptic bronchoscope,
      employing a 21-gauge, 1.3 cm aspirating needle. They were preceded by bronchial
      brushing and followed by transbronchial biopsy (TBB) of the peripheral lesion. In
      two cases, the apical nodules were not accessible by any of these procedures.
      Bronchial washings were also collected immediately after each procedure (brush,
      TBNA and TBB). TBNA was diagnostic in 23 of 37 patients (62%) rendering the TBNA
      yield considerably higher than washing (24%), brushing (27%) or TBB (38%). The
      addition of TBNA to the combination of TBB, brushing and washing, significantly
      increased the yield of fibreoptic bronchoscopy in our series from 46% to 70%. No
      significant complications, such as pneumothorax or major bleeding, occurred
      either with TBNA or TBB. In conclusion, our findings suggest that transbronchial
      needle aspiration is a safe procedure, that can improve the diagnostic yield of
      bronchoscopy in the diagnosis of peripheral lung masses or nodules.

PMID- 7589385
TI  - Acute respiratory effects of low level summer smog in primary school children.
AB  - We aimed to study the possible effects of exposure to a summer smog episode on
      the respiratory health of 212 school children. Furthermore, the suitability of
      the forced oscillation technique (FOT) to demonstrate such effects was evaluated.
      Acute respiratory symptoms were evaluated by questionnaire and lung function was
      assessed by spirometry and respiratory impedance measurements. For each child,
      comparisons were made between measurements performed at baseline (low levels of
      air pollutant: 55 micrograms.m-3 for SO2 and 58 micrograms.m-3 for NO2 (maximum
      24 h means); O3 levels ranged from 2-56 micrograms.m-3 (8 h mean)); and after a
      summer smog episode (characterized by 8 h O3 levels > 120 micrograms.m-3 (163
      micrograms.m-3) and 1 h levels > 160 micrograms.m-3 (215 micrograms.m-3). No
      significant effects were observed on the prevalence of acute respiratory
      symptoms. When individual changes in lung function indices (delta LF) were
      regressed on changes in previous day ozone (8 h mean) and changes in mean daily
      temperature (delta MTemp), using multiple linear regression analysis, a
      significant negative association was observed with peak expiratory flow (PEF),
      but not with other spirometry indices. Although significant associations were
      observed with reactance at 8 Hz (Xrs8), resonant frequency (f0) and frequency
      dependence of resistance (FD), the signs of the beta s were opposite to the
      direction expected when O3 adversely affected the impedance outcomes. In
      conclusion, in this study short-term exposure to moderately high levels of ozone
      did not result in clear adverse effects on the respiratory health of the
      children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589386
TI  - Respiratory effects of air pollutants: experimental studies in humans.
AB  - Epidemiological and environmental chamber studies in man, and toxicological
      studies in animals, have provided valuable insights into the biological effects,
      the mechanisms of action, and the dose-response characteristics of some major air
      pollutants. This review describes the information currently available on air
      pollutant effects in man, as the result of experimental studies. There are
      certain advantages, as well as some limitations, in human chamber exposure
      studies, but if carefully designed and based upon relevant background data they
      may give information that is valuable for understanding the effects of air
      pollutants in man. Reversible effects on the airway mechanics, the responsiveness
      of the airways to methacholine and allergen have been shown to be caused by air
      pollutants. Furthermore, significant changes have been demonstrated in airway
      permeability, bronchoalveolar lavage, nasal lavage, and peripheral blood cells
      and inflammatory markers. Currently, human toxicology to air pollutants is a
      progressive research area.

PMID- 7589388
TI  - Sleep and breathing: actual insight and perspectives.

PMID- 7589387
TI  - Theophylline and selective phosphodiesterase inhibitors as anti-inflammatory
      drugs in the treatment of bronchial asthma.
AB  - Theophylline has been in clinical use for the treatment of bronchial asthma and
      other respiratory diseases for well over 50 yrs. Over this time, a considerable
      body of evidence has accumulated to show that this drug has a wide range of
      pharmacological actions, in addition to the well-recognized action on airway
      smooth muscle function. Current evidence suggests that part of the therapeutic
      value of theophylline in the treatment of asthma is by virtue of an anti
      inflammatory or immunomodulatory effect, although the actual mechanism of action
      remains unclear. It has been proposed that the observed anti-inflammatory effects
      of theophylline could be attributed to phosphodiesterase (PDE) inhibition, and
      recently the type III and IV isoenzymes have been characterized in a number of
      inflammatory cells. This article reviews the evidence that theophylline and the
      newer more selective type IV PDE isoenzyme inhibitors can inhibit the activation
      of inflammatory cell types, such as T-lymphocytes, eosinophils, mast cells and
      macrophages, in vitro. The evidence supporting the ability of theophylline and
      selective PDE IV isoenzyme inhibitors to modify allergic inflammation both in
      animal models and clinical asthma is also discussed. We conclude that
      theophylline possesses important anti-inflammatory and immunomodulatory activity
      and that, in light of this evidence, it is timely to reconsider the place of
      theophylline in the treatment of asthma.

PMID- 7589389
TI  - Drug resistant tuberculosis: back to sanatoria, surgery and cod-liver oil?

PMID- 7589391
TI  - Chemokines in bronchoalveolar lavage fluid in summer-type hypersensitivity
      pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease
      caused by the inhalation of a variety of antigens and is characterized by a
      dramatic accumulation of inflammatory cells, including neutrophils, lymphocytes
      and macrophages, in the lung. The mechanisms implicated in the inflammatory cell
      recruitment observed in hypersensitivity pneumonitis are unknown. We examined the
      concentrations of two important chemokines, interleukin-8 (IL-8) and monocyte
      chemoattractant protein-1/monocyte chemotactic and activating factor (MCP
      1/MCAF), in the bronchoalveolar lavage fluid (BALF) of patients with summer-type
      hypersensitivity pneumonitis (n = 8), and compared them with those in patients
      with sarcoidosis (n = 13) and with controls (n = 8). In the BALF of summer-type
      hypersensitivity pneumonitis, the levels both of IL-8 and MCP-1 were
      significantly increased compared with levels measured in control subjects. On the
      other hand, compared to the control value, the MCP-1 level in the BALF of the
      sarcoidosis patients was significantly increased, but IL-8 was only slightly and
      nonsignificantly increased. Since IL-8 is a chemoattractant for neutrophils and T
      lymphocytes, whereas MCP-1 acts mainly on monocytes/macrophages, our findings may
      indicate that these two chemokines participate in the cellular accumulation
      observed in hypersensitivity pneumonitis.

PMID- 7589390
TI  - Drug-resistant tuberculosis in northern Germany: a retrospective hospital-based
      study of 1,055 patients from 1984 until 1993.
AB  - For the past decade, there have been no data on the time course of drug resistant
      tuberculosis and on risk factors for drug resistance in former West Germany. We
      reviewed the medical records of all patients with positive cultures for
      Mycobacterium tuberculosis from 1984 until 1993 in a hospital near Hamburg. Drug
      susceptibility testing was performed for isoniazid, rifampicin, ethambutol, and
      streptomycin, using the modified proportion method. Of 1,055 patients, 9.6% had
      isolates resistant to one or more drugs. Of the isolates, 5.8% showed resistance
      to isoniazid or rifampicin and 1.8% to both isoniazid and rifampicin. There was
      no significant change of the resistance rate during the study period. Twenty six
      percent of 89 patients from South America, Africa or Asia had isolates resistant
      to one or more drugs, compared with 7.6% of 799 patients born in Germany (odds
      ratio (OR) 4.2; 95% confidence interval (95% CI) 2.5-7.3). Among patients born in
      Germany, 32% of 101 patients with a history of prior anti-tuberculosis drug
      therapy had resistant organisms, versus 4.2% of 698 patients without prior
      therapy (OR 10.7; 95% CI 6.1-18.7). Resistance rates for 35 patients, who had
      been treated within the last 5 yrs, and for 65 patients, who had been treated
      more than 5 yrs ago, were 57 and 17%, respectively (OR 6.6; 95% CI 2.9-16.6). Our
      results suggest that there is no increase in the proportion of drug-resistant
      tuberculosis in our hospital, and that patients with a recent history of
      antituberculosis drug therapy and patients from South America, Africa, or Asia
      are at high risk for drug resistance.

PMID- 7589392
TI  - Treatment of steroid-dependent bronchial asthma with cyclosporin.
AB  - The treatment of chronic severe asthma is unsatisfactory for many patients. The
      aim of the study was to determine the effects of treatment of steroid-dependent
      asthma with cyclosporin. We performed a double-blind, placebo-controlled,
      randomized, parallel group trial on the effect of cyclosporin on pulmonary
      function, asthma severity and tapering of prednisone in 34 steroid-dependent
      asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1)
      baseline period (12 weeks); 2) experimental period divided into two parts: Part I
      (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or
      placebo treatment and oral prednisone reduction; and 3) follow-up observation (8
      weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory
      flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in
      one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile
      and blood cyclosporin levels were monitored throughout the study. Following
      cyclosporin administration, a slight beneficial effect on some subjective
      parameters of asthma severity was observed. At the same time, no beneficial
      effect on pulmonary function was noted. The time trends analysis of mean daily
      prednisone doses between the treatment groups revealed a statistically
      significant difference indicating that, during prednisone reduction, cyclosporin
      seemed to be slightly more efficient than placebo in reducing the requirement for
      systemic corticosteroid, even though the steroid reduction was accompanied by
      slight impairment of some pulmonary function. However, there was no significant
      difference in the final dose reduction between the treatment groups. These data
      and the known toxicity of the drug suggest a limited place for cyclosporin
      treatment in steroid-dependent bronchial asthma.

PMID- 7589393
TI  - Allergen-induced late-phase airways obstruction in the pig: mediator release and
      eosinophil recruitment.
AB  - The aim of this study was to develop a novel model for studies of mediator
      mechanisms involved in the late asthmatic reaction in the lower airways, by using
      the sensitized pig. The release of histamine and cysteinyl-containing
      leukotrienes (cys-LTs), as well as the levels of inflammatory cells in blood and
      bronchoalveolar lavage fluid, were determined and their relationship to plasma
      cortisol levels and pulmonary airways obstruction was noted. Specific-pathogen
      free pigs were actively sensitized with Ascaris suum allergen, and one group of
      animals was treated with a cortisol-synthesis inhibitor (metyrapone) by constant
      intravenous infusion. Ascaris suum allergen was nebulized into the lower airways
      and total lung resistance, blood leucocyte count and urinary levels of
      methylhistamine and leukotriene E4 (LTE4) were followed for 8 h, whereafter
      bronchoalveolar lavage was performed for analysis of leucocytes. An increase in
      urinary methylhistamine and LTE4 was seen during the acute allergic reaction in
      both groups of pigs. Metyrapone treatment prolonged the acute release of
      histamine, and this was seen together with a prolonged acute bronchoconstrictor
      response. In metyrapone-treated pigs, a continuous release over 8 h was seen for
      cys-LTs, but not for histamine. A late blood eosinophilia was also seen in
      metyrapone-treated animals, starting 4-6 h after allergen challenge. Late cys-LT
      release and eosinophilia were absent in non-metyrapone-treated animals. These
      results suggest that allergen-induced late release of cys-LTs as well as blood
      eosinophilia occur simultaneously with late-phase airways obstruction in the pig,
      and that all these reactions are prevented by high levels of endogenous cortisol.

PMID- 7589394
TI  - Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough
      induced by citric acid in the unanaesthetized guinea pig.
AB  - It is now well-established that sensory nerves stimulation in the airway induces
      bronchoconstriction and inflammation, but also protective reflexes, such as
      coughing. These effects are mediated through the release of tachykinins
      (substance P and neurokinin A) and we have recently shown that SR 48968, a
      tachykinin NK2-receptor antagonist, inhibited cough induced by citric acid. In
      this paper, we have studied the effects of SR 48968 administered by aerosol. We
      have also investigated the effects of SR 140333, a tachykinin NK1-receptor
      antagonist, and the combination of both SR 48968 and SR140333 to determine
      whether tachykinin NK1 receptors are involved in cough. Finally, we have studied
      the combined effects of SR 48968 and salbutamol to find out whether the
      antitussive effect of SR 48968 is a consequence of the inhibition of
      bronchoconstriction. Unanaesthetized guinea-pigs were placed in a transparent
      chamber and exposed to an aerosol of citric acid (0.4 M). The number of coughs
      was counted by visual inspection and by determination of sounds and pressure
      variations in the chamber. By the aerosol route, SR 48968 was an efficient
      antitussive and 16 times more potent than codeine. SR 140333 (0.1-1 mg.kg-1 i.p.)
      did not exert any antitussive effect but it potentiated the maximal effect
      induced by SR 48968. Finally, salbutamol, in a dose (0.3 mg.kg-1) which inhibits
      bronchoconstriction, but not cough induced by citric acid, did not modify the
      antitussive effect of SR 48968.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589395
TI  - Quantitative analysis of parenchymal and vascular alterations in NO2-induced lung
      injury in rats.
AB  - Nitrogen dioxide (NO2), the oxidation product of nitric oxide (NO), is a reactive
      free radical forming gas, the inhalation of which has been reported to induce
      severe damage to distal airways. In order to quantify dose and time course of
      parenchymal and vascular damage, rats were exposed to 5, 10 and 20 ppm NO2 for 3
      and 25 days, followed by quantitative histology and morphometry of the lung.
      Histological investigations of the short-term exposed animals showed structural
      alterations extending from slight interstitial oedema after exposure to 5 ppm, to
      epithelial necrosis and interstitial inflammatory infiltration after exposure to
      10 ppm, and an additional intra-alveolar oedema after 20 ppm. The pulmonary
      arteries disclosed no qualitative changes, such as muscularization of intra
      acinar vessels. Long-term exposure to 10 ppm and 20 ppm NO2 resulted in emphysema
      and slight centrilobular interstitial fibrosis. Morphometric analysis revealed
      the alveolar surface density to be significantly diminished after short-term
      exposure to 20 ppm NO2 and long-term exposure to 10 and 20 ppm NO2. The medial
      thickness of pulmonary arteries was significantly increased after short- and long
      term exposure to 20 ppm NO2 and long-term exposure to 10 ppm NO2. In the 5 ppm
      short- and long-term exposure groups the pulmonary arterial medial thickness was
      significantly decreased compared to controls. Correlation analysis revealed a
      negative correlation between average medial thickness and alveolar surface
      density (coefficient of correlation: -0.56). We conclude that the extent of NO2
      induced pulmonary parenchymal and vascular alterations are closely related and
      concentration- and time-dependent.

PMID- 7589396
TI  - Capillary pressure estimates from arterial and venous occlusion in intact dog
      lung.
AB  - We performed pulmonary venous occlusions in order to check the validity of the
      pulmonary capillary pressure measurements obtained using pulmonary arterial
      occlusion in the intact animal. The venous and arterial postocclusion pressure
      profiles were recorded using balloon catheters introduced, respectively, into a
      left lower lobe vein and into a right pulmonary artery in the anaesthetized open
      chest dog. The pressure profiles were fitted by a biexponential function with an
      early exponential and a late exponential presenting, respectively, a short and a
      long time constant. We used the zero-time extrapolation of the late slow
      exponential to obtain an arterial (Pc,ao) and a venous (Pc,vo) estimate of the
      pulmonary capillary pressure. Each Pc,ao and Pc,vo made it possible to calculate
      a fractional arterial or venous pressure gradient when referenced to the
      arteriovenous pressure gradient measured during the occlusion process. In nine
      dogs, when referenced to the whole lung, the arterial, middle and venous
      fractional pressure gradients were 37 +/- 11, 10 +/- 6, and 53 +/- 12%,
      respectively. As the middle fractional pressure gradient is low, we conclude that
      pulmonary capillary pressure estimates from arterial occlusion are close to the
      venous occlusion estimates of capillary pressure in the intact dog lung.

PMID- 7589397
TI  - Ventilatory muscle strength and endurance in myasthenia gravis.
AB  - Patients with generalized myasthenia gravis (MG) often have associated
      ventilatory muscle involvement. It is not known whether patients with isolated
      ocular muscle involvement have identifiable involvement of their ventilatory
      muscles. Most studies have assessed muscle involvement by measuring muscle
      strength; however, we hypothesized that measures of ventilatory muscle endurance
      may be more sensitive tests of ventilatory muscle involvement in myasthenia
      gravis. We studied 17 patients with myasthenia gravis (four with ocular
      involvement alone and 13 with varying degrees of generalized myasthenia gravis).
      Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory
      pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test)
      were measured before and 20 min after i.m. neostigmine. We compared the results
      with those of 10 normal controls. We found no difference between patients with
      isolated ocular involvement and controls. Ocular myasthenia gravis patients did
      not improve after neostigmine. The patients with generalized myasthenia gravis
      had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of
      predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved
      = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls.
      After neostigmine, there was a significant increase in MIP in patients with
      generalized myasthenia gravis and a trend towards an increased MEP. As a group,
      the patients with generalized myasthenia gravis did not demonstrate a change in
      their ventilatory muscle endurance after neostigmine; however, there was
      considerable interpatient variability in response. We conclude that patients with
      isolated ocular MG have normal ventilatory muscle strength when tested
      conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589398
TI  - Discriminant analysis on small cell lung cancer and non-small cell lung cancer by
      means of NSE and CYFRA-21.1.
AB  - A correct diagnosis of small cell lung cancer (SCLC) and non-small cell lung
      cancer (NSCLC) is essential both for prognostic and therapeutic reasons. We used
      discriminant analysis as a method to optimize the discriminant power of serum
      tumour marker levels for differentiation between SCLC and NSCLC. A panel of serum
      markers, including neurone specific enolase (NSE), cytokeratin fragment antigen
      21.1 (CYFRA-21.1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen
      (CEA) was obtained in 50 consecutive NSCLC and 17 SCLC. Data were analysed by the
      BMDP statistical program after logarithmic transformation of marker levels. The
      variables selected were NSE and CYFRA-21.1. Considered together, they were able
      to give a 97% rate of correct classification. The formula generated (canonic
      variable, CV) was validated on a group of seven SCLC and 22 NSCLC patients. Only
      two errors occurred. We therefore conclude that the canonic variable tested,
      based on NSE and CYFRA-21.1, provides a good discrimination between the two types
      of lung cancer. The method is rapid, relatively inexpensive, and based on simple
      serum tests.

PMID- 7589399
TI  - Pulmonary function during the first year of life in healthy infants born
      prematurely.
AB  - Premature birth is associated with increased respiratory morbidity. We
      investigated cross-sectionally, in 69 healthy infants who had never had
      cardiorespiratory problems, whether premature birth is associated with diminished
      pulmonary function. The study comprised 26 healthy infants born prematurely (PT),
      median gestational age 32 (26-36) weeks, and 43 healthy controls born full-term
      (FT), median gestational age 40 (37-42) weeks. Static respiratory system
      compliance (Crs) was assessed by weighted spirometry, combined with the
      measurement of the functional residual capacity by closed circuit helium dilution
      (FRCHe) and with assessment of ventilation distribution from the mixing index
      (MI). Repeatability of these indices was also assessed. Premature and full-term
      infants had the same length-corrected FRCHe; their Crs was different, but the
      difference disappeared when gestational age was taken into account. Mixing index
      was unrelated to body size and was not different between full-term and premature
      infants. Crown-heel length and lung volume were not different for any
      postconceptional age. However, infants born prematurely were smaller and had
      smaller lung volume at any postnatal age compared to those born at term.
      Repeatability of the indices was fair. These findings suggest that gestational
      age < 37 weeks is associated with normal respiratory system mechanics for body
      size, and normal distribution of ventilation in healthy infants who never had
      cardiorespiratory problems.

PMID- 7589400
TI  - Eosinophil cationic protein and tidal flow volume loops in children 0-2 years of
      age.
AB  - Many children with recurrent wheezing in early childhood develop asthma.
      Objective parameters to describe different groups of wheezers are limited, but
      tidal flow volume (TFV) response to inhaled salbutamol has demonstrated
      differences between children with and without asthma. Also, eosinophil cationic
      protein (ECP) has been associated with declining lung function in older children.
      We therefore investigated whether lung function and serum ECP (s-ECP) could
      differentiate between groups of wheezy young children. TFV loops were measured in
      79 awake children (mean age 14 months). Minimum two wheezy episodes (mean 3.2) or
      minimum 4 weeks persistent wheeze were reported in 41 children (cases), whereas
      the 38 controls had no history of wheeze. Airways responsiveness (change in ratio
      of time until peak expiratory flow to total expiratory time (tPEF/tE) after
      inhaled nebulized salbutamol) was measured in 26 cases and 24 controls. Serum ECP
      and serum myeloperoxidase (s-MPO) were measured in all children. Cases had
      significantly lower mean tPEF/tE (0.21) than controls (0.33), and higher mean s
      ECP (21.9 micrograms.L-1) than controls (14.0 micrograms.L-1). Serum ECP (but not
      s-MPO) correlated significantly with the percentage change in tPEF/tE from
      baseline (r = 0.7), but not with initial tPEF/tE. Serum ECP increased
      significantly with increasing immunoglobulin E (IgE), airways responsiveness and
      eosinophil count, but decreased with increasing age. TFV responsiveness to
      salbutamol and s-ECP levels correlate strongly, both probably reflecting airways
      inflammation, and may possibly be valuable prognostic tools in recurrent wheezy
      infants and toddlers.

PMID- 7589402
TI  - Pathophysiology of obstructive sleep apnoea.
AB  - The pathophysiology of obstructive sleep apnoea (OSA) is complex and incompletely
      understood. A narrowed upper airway is very common among OSA patients, and is
      usually in adults due to nonspecific factors such as fat deposition in the neck,
      or abnormal bony morphology of the upper airway. Functional impairment of the
      upper airway dilating muscles is particularly important in the development of
      OSA, and patients have a reduction both in tonic and phasic contraction of these
      muscles during sleep when compared to normals. A variety of defective respiratory
      control mechanisms are found in OSA, including impaired chemical drive, defective
      inspiratory load responses, and abnormal upper airway protective reflexes. These
      defects may play an important role in the abnormal upper airway muscle responses
      found among patients with OSA. Local upper airway reflexes mediated by surface
      receptors sensitive to intrapharyngeal pressure changes appear to be important in
      this respect. Arousal plays an important role in the termination of each apnoea,
      but may also contribute to the development of further apnoea, because of
      reduction in respiratory drive related to the hypocapnia which results from
      postapnoeic hyperventilation. A cyclical pattern of repetitive obstructive
      apnoeas may result. A better understanding of the integrated pathophysiology of
      OSA should help in the development of new therapeutic techniques.

PMID- 7589401
TI  - Prevalence and characteristics of children with chronic respiratory symptoms in
      eastern Finland.
AB  - The objective of the present study was to assess the prevalence of asthma and
      asthma-related symptoms in Finland. We also wondered whether chronic cough may be
      an indicator of occult asthma. Prevalence and characteristics of children with
      doctor-diagnosed asthma and chronic respiratory symptoms were investigated in 7
      12 year old school children from eastern Finland by using a questionnaire on
      respiratory symptoms. In addition, skin-prick tests, flow-volume spirometry, and
      serum total immunoglobulin E (IgE) measurements were performed in children
      reporting chronic respiratory symptoms. The parent-reported prevalence of doctor
      diagnosed asthma was 4.4%, of wheezing 5.4%, of attacks of shortness of breath
      with wheezing 4.6%, and of dry cough at night 12%. Children with dry cough only
      (n = 195) had less frequent parental asthma, self-reported allergies, daily
      respiratory medication, and moisture stains or molds at home than asthmatic
      children (n = 180), but these findings were more frequent than among asymptomatic
      children (n = 2,169). The prevalence of at least one positive skin-prick test
      result was 79% among the asthmatic children and 55% among children with dry cough
      only. There were no differences between the two symptom groups in serum total IgE
      levels and spirometric lung functions, except in maximal mid-expiratory flow
      (MMEF) values, which were significantly lower among children with asthmatic
      symptoms. The present results support the hypothesis that chronic cough may be an
      indicator of occult asthma. Therefore, to improve the sensitivity of respiratory
      questionnaires designed to detect asthma, they should also include questions on
      chronic cough.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589403
TI  - PDE isoenzymes as targets for anti-asthma drugs.
AB  - Phophodiesterase (PDE) isoenzyme profiles of human cell preparations and tissues
      have been analysed by a semiquantitative method using selective PDE inhibitors
      and activators. Neutrophils, eosinophils and monocytes contain PDE IV
      exclusively. Lymphocytes, alveolar macrophages and endothelial cells contain PDE
      IV and PDE III, and in addition, PDE I is measured in macrophages and PDE II in
      endothelial cells. These basal cell-specific PDE isoenzyme profiles appear to be
      modified by: 1) substrate concentration; 2) kinase-dependent phosphorylation; and
      3) regulated rate of synthesis. Therefore, PDE isoenzyme profiles represent
      dynamic patterns, which apparently adapt to pathological and environmental
      conditions. In parallel functional studies, the influence of mono-selective
      (rolipram, PDE IV; motapizone, PDE III), dual-selective (zardaverine) and non
      selective (theophylline) PDE inhibitors were compared. Corresponding to isoenzyme
      analysis, it was demonstrated that both PDE III and PDE IV have to be inhibited
      for complete suppression of either tumour necrosis factor-alpha (TNF-alpha)
      release from macrophages, or lymphocyte proliferation (PDE III/IV cells). In
      eosinophils (PDE IV cells) platelet-activating factor (PAF)-induced chemotaxis or
      C5a-stimulated degranulation are only weakly inhibited by rolipram alone. After
      addition of a beta 2-agonist, however, the efficacy of rolipram is enhanced due
      to concomitant influence of synthesis and breakdown of cyclic adenosine
      monophosphate (cAMP). Theophylline inhibits PDE isoenzyme activities and
      functions of inflammatory cells with similar potency, and exhibits higher
      functional efficacy as compared to rolipram.

PMID- 7589404
TI  - Drug-resistant tuberculosis in the 1990s.
AB  - There has been an upsurge of tuberculosis in many parts of the world in the past
      decade. The high rates of drug-resistant tuberculosis currently reported in many
      countries are alarming. The most catastrophic phenomenon is the emergence of
      multidrug-resistant strains of Mycobacterium tuberculosis. These organisms have
      caused epidemic outbreaks in nosocomial and health-care settings in the USA and
      some European countries. In addition to immigration, poverty, alcoholism and
      intravenous substance abuse, human immunodeficiency virus (HIV) infection has
      also had a significant impact on the prevalence of drug resistance, since amongst
      these patient groups a common factor giving rise to drug resistance is
      noncompliance. Rapid drug susceptibility tests are needed, and effective
      chemotherapy regimens with newly developed drugs in combination with traditional
      second-line antituberculosis agents for established multidrug-resistant
      tuberculosis are urgently being sought. There is also a quest for other novel
      modalities of therapy. Measures should be actively adopted to prevent the
      development of drug resistance. Well formulated short-course chemotherapy as
      initial treatment and ensurance of compliance are the most important components.
      The organization of a national tuberculosis control programme with a sound and
      adequately functioning infrastructure remains the most effective strategy to
      combat the resurgence of tuberculosis and to curtail drug resistance.

PMID- 7589405
TI  - Neurophysiology of the cough reflex.
AB  - Cough is due to activation of sensory receptors in the larynx and lower
      respiratory tract, sending impulses to the brainstem. The central organization of
      cough is poorly understood. The afferent pathways for cough are from receptors in
      and under the epithelium of the airways. These receptors are rapidly adapting,
      with thin myelinated fibres in the vagus nerves, which can be directly stimulated
      by tussive agents. Activation of C-fibre receptors in the airway releases sensory
      neuropeptides. These cause neurogenic inflammation and may activate rapidly
      adapting receptors to cause cough. The central connections of the C-fibre
      receptors inhibit cough. Thus, the sensitivity of the cough reflex and its
      pattern of response is due to a complex interaction between C-fibre receptors and
      rapidly adapting receptors, with peripheral and central nervous interactions. How
      these mechanisms apply to clinical cough in patients is at present poorly
      understood, but is beginning to be clarified.

PMID- 7589406
TI  - Leukotriene receptor antagonists and biosynthesis inhibitors: potential
      breakthrough in asthma therapy.
AB  - Cysteinyl leukotrienes are potent bronchoconstrictors, inducers of airway
      microvascular leakage and oedema, and of mucus secretion, in addition to causing
      an eosinophilic airway infiltration. Increased urinary excretion of the cysteinyl
      leukotriene E4 (LTE4) has been demonstrated following allergen challenge and
      during acute asthma attacks. Strategies for inhibition of cysteinyl leukotriene
      effects include antagonism of cysteinyl leukotriene receptors and inhibition of 5
      lipoxygenase activity. In experimental challenge studies in asthmatic patients,
      these compounds can inhibit bronchoconstriction in response to exercise, aspirin
      and allergen. Results from clinical studies using receptor antagonists, such as
      ICI 204,219 and MK-571, and synthesis inhibitors, such as zileuton, demonstrate
      beneficial effects, with improvement in symptoms and forced expiratory volume in
      one second (FEV1), and a reduction in the use of beta 2-adrenergic relief
      medication. Further studies are needed to clarify the exact mechanisms by which
      these compounds provide beneficial effects. Cysteinyl leukotrienes are important
      mediators of asthma, and inhibition of their effects may represent a potential
      breakthrough in the therapy of asthma.

PMID- 7589407
TI  - Comparison of twenty three nebulizer/compressor combinations for domiciliary use.
AB  - We have assessed the physical and dynamic characteristics of 23 home jet
      nebulizer/compressor combinations currently available in the UK and Europe. The
      combinations were evaluated in terms of pressure-flow characteristics, aerosol
      mass distribution, volume output, electrical costs, and sound level. In addition,
      we determined the effect of nebulizer fill volume on aerosol mass distribution
      and volume output. One nebulizer was used with six different compressors, and
      four compressors were tested with three different nebulizers. The pressure-flow
      relationships showed a wide variation between models, as did flow-rate at the
      nebulizer (range 3.0-8.0 L.min-1). The mean +/- SD volume nebulized after 10 min
      using an initial fill volume of 2.5 and 5.0 mL was 46 +/- 9 and 34 +/- 12%,
      respectively. The mass median aerodynamic diameter (MMAD) over a 5 min
      nebulization ranged 2.6 to 10.2 microns. Nine of the nebulizations produced an
      MMAD of less than 5 microns at both fill volumes. Changing nebulizer/compressor
      combinations affected flow rate, MMAD and volume output. Sound levels varied
      between models. Running costs were low, with all using less than 74 kilowatt
      hours of energy per year. We conclude that there is a wide variation in
      performance of nebulizer/compressor combinations for use with nebulized
      bronchodilators. Correct matching of the nebulizer/compressor is seen to be
      important to ensure optimum performance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589408
TI  - Servocontrolled generator to measure respiratory impedance from 0.25 to 26 Hz in
      ventilated patients at different PEEP levels.
AB  - Assessing respiratory impedance (Zrs) in ventilated patients over a wide
      frequency band, ranging from breathing rates to typical forced oscillation
      frequencies, during end-expiratory pauses at different positive end-expiratory
      pressures (PEEP) is of potential interest to assess a patient's respiratory
      mechanics. Zrs measurements under these conditions are not possible with the
      present variants of the forced oscillation technique. The aim of this work was to
      design a forced oscillation generator operating from spontaneous breathing
      frequencies whilst withstanding PEEP. To this end, we constructed a generator
      based on a servocontrolled loudspeaker. This allowed the loudspeaker cone to
      remain at its resting position regardless of the external PEEP applied. The
      system was optimized by using a mechanical analogue. The clinical applicability
      of the servocontrolled generator was assessed by measuring Zrs in mechanically
      ventilated chronic obstructive pulmonary disease (COPD) patients during end
      expiratory pauses at different transrespiratory pressures. The forced oscillation
      generator designed may be easily applicable in practice since it is small and
      light. The system is able to withstand transrespiratory pressures of up to 17 hPa
      and allows the application of forced oscillation of sufficient amplitude ( > 2
      hPa peak-to-peak, 0.25-26 Hz) to obtain reliable respiratory resistance and
      reactance data. The servocontrolled generator permits the assessment of
      respiratory mechanics over a wide frequency band ranging from breathing
      frequencies to the most typical forced oscillation frequencies during end
      expiratory pauses at PEEPs within the conventional range.

PMID- 7589409
TI  - Haemodynamics and gas exchange before and after coil embolization of pulmonary
      arteriovenous malformations.
AB  - A complete description of haemodynamics and gas exchange before and after
      percutaneous coil embolization of multiple pulmonary arteriovenous malformations
      is reported in a 45 year old woman with hereditary haemorrhagic telangiectasis
      (HHT). Before treatment, whilst the patient complained of severe dyspnoea during
      daily activities, an intrapulmonary shunt of 31% was measured (inert gas
      elimination technique), together with a cardiac output (thermodilution technique)
      of 12.4 L.min-1, resulting in a resting arterial oxygen tension (PaO2) of 8.53
      kPa. Effective occlusion of all visible pulmonary malformations resulted in a
      rapid and major improvement in exercise tolerance, whilst resting PaO2 remained
      almost unchanged. A second investigation performed 4 months after treatment
      revealed a persistent intrapulmonary shunt of 19%, a cardiac output of 7.35 L.min
      1, and a resting PaO2 of 10.53 kPa. We conclude that major increases in cardiac
      output largely contribute to the maintenance of PaO2 in patients with multiple
      pulmonary arteriovenous malformations and intrapulmonary shunt. The benefit of
      coil embolization is due both to an improvement in arterial oxygenation and a
      normalization of cardiac output.

PMID- 7589410
TI  - Non-small-cell lung cancer with multiple paraneoplastic syndromes.
AB  - We describe the case of a patient with multiple paraneoplastic syndromes, six in
      total, associated with a non-small-cell cancer of the lung. In this single
      patient we found hypertrophic pulmonary osteoarthropathy, hyperkeratosis of palms
      and soles, erythema annulare centrifugum, syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH), and ectopic andrenocorticotrophic hormone (ACTH)
      and calcitonin production.

PMID- 7589411
TI  - Chylothorax and chylous ascites due to heart failure.
AB  - Chylous ascites and chylothorax have rarely been reported as a consequence of
      severe right heart failure. To our knowledge, this is the first case report of
      both disorders occurring as a result of ischaemic cardiomyopathy. The autopsy
      findings and possible mechanisms of production are discussed.

PMID- 7589413
TI  - Exposure to environmental tobacco smoke and risk of lung cancer: the
      epidemiological evidence.

PMID- 7589412
TI  - Inflammatory bronchial polyps associated with asthma: resolution with inhaled
      corticosteroid.
AB  - In a 50 year old man who complained of cough and sputum, a small endobronchial
      tumour was found in the left main bronchus and was biopsied via bronchoscopy. The
      histological diagnosis was inflammatory polyp with marked infiltration of
      eosinophils. Six years later, the patient developed asthma. At the same time,
      another polyp was found in the posterior basal bronchus of the right lower lobe.
      The appearance of the first polyp was unchanged endoscopically and
      histologically. Inhalation of beclomethasone dipropionate, 200 micrograms b.i.d.,
      was started and symptoms of asthma soon subsided. In addition, the two polyps
      regressed and eventually disappeared after one year of treatment. Inhaled
      corticosteroids, being noninvasive and relatively safe, appear to be a possible
      therapeutic option in inflammatory bronchial polyps, especially in cases where
      the patient has asthma as an underlying condition, or the polyps are small and
      their management is not urgent.

PMID- 7589415
TI  - Debriefing the family: is research an intervention?
AB  - The primary focus of this article is to examine the general assumption that
      families are left largely unchanged by their participation in research, and to
      question whether family research can have unintended positive or negative effects
      on participants. The present article reports feedback from families participating
      in the Nonshared Environment and Adolescent Development project, a longitudinal
      study of family process and adolescent development. Families differed in their
      perceptions about whether the research experience was positive, detrimental, or
      inconsequential. This feedback underscores the researcher's ethical
      responsibility to detect and remove deleterious effects of participation.
      Suggestions are made for providing adequate debriefing to subjects and for using
      debriefing as a research tool to study the interaction between researcher and
      families.

PMID- 7589414
TI  - Psychoeducational multiple family groups: four-year relapse outcome in
      schizophrenia.
AB  - Earlier studies of family psychoeducation and clinical reports on multiple family
      groups (MFGs) have reported substantial reductions in relapse rates for patients
      with schizophrenia. These groups offer an expanded social network and thereby may
      confer a margin of protection against relapse. However, to date, there has not
      been an empirical trial of this modality. The advent of family psychoeducational
      and behavioral management strategies provided the basis for an experimental,
      three-way comparison of psychoeducational MFGs to psychoeducation in a single
      family format and to MFGs without psychoeducation, using symptomatic relapse as
      the outcome criterion. After 4 years, the psychoeducational MFGs were
      significantly more effective in extending remission than the single-family
      format, while the MFGs without psychoeducation approximated outcome in the
      psychoeducational MFGs. The respective relapse rates at 4 years were 50%, 78%,
      and 57%; MFGs averaged 12.5% and 14% per year. These results point toward an
      enhanced and independent, long-term therapeutic effect for multiple family
      groups, when combined with antipsychotic medication and psychoeducation, with
      especially promising cost-effectiveness.

PMID- 7589416
TI  - An empirically derived typology of families: I. Relationships with adult health.
AB  - In this report we describe the development and partial validation of an
      empirically derived typology of families based on 11 family variable composites
      derived from the California Family Health Project. Our goal was to use the
      typology to condense and integrate the findings from previous analyses of a large
      group of family variables and to account for differences in the self-reported
      health of adult family members. Exploratory and confirmatory cluster analyses
      conducted separately by gender classified 97% of the sample into four parallel
      types for husbands and wives: Balanced, Traditional, Disconnected, and
      Emotionally Strained. A 1-way MANOVA indicated that all 11 family variable
      composites significantly differentiated the four family types for husbands and
      wives. Significant differences among the four family types were also found on 10
      demographic and other family variables, using ANOVA. Using MANOVA, we compared
      the four family types on 12 self-reported health and well-being variables by
      gender. Both husbands and wives from Balanced and Traditional families reported
      higher health scores than spouses from Disconnected and Emotionally Strained
      families, but no single profile of health scores was unique to a particular
      family type. The four family types provide an integrated and comprehensive
      framework for describing the family in health research.

PMID- 7589417
TI  - An empirically derived typology of families: II. Relationships with adolescent
      health.
AB  - In this report from the California Family Health Project, we describe the
      relationship between an empirically derived family typology based on parent data,
      and the self-reported health and well-being of 151 adolescent offspring. The
      typology is comprised of four family types: Balanced, Traditional, Disconnected,
      and Emotionally Strained. Three adolescent health indices were constructed from
      13 self-reported health variables using principal components and multidimensional
      scaling analyses: Physical Health, Emotional Health, and Alcohol Abstinence.
      ANOVA indicated that Physical Health was significantly different among
      adolescents in the four family types. The findings varied, however, depending
      upon whether the typology was based on mothers' or fathers' appraisals of the
      family. In the father-based typology, adolescents from Traditional families
      scored highest while those from Emotionally Strained and Balanced families scored
      lowest. In the mother-based typology, adolescents from Balanced, Traditional, and
      Emotionally Strained families scored equally high, while those from Disconnected
      families scored significantly lower than those from the other three family types.
      Differences on Abstinence were significant only in the father-based typology.
      Adolescents from Traditional and Emotionally Strained families drank less than
      adolescents from Disconnected families. No significant differences among
      adolescents were found for Emotional Health, and adolescent gender did not
      interact significantly with family type to affect any of the three health
      indices. Traditional and Disconnected family types had offspring who clearly
      stood apart with higher and lower health scores, respectively. The results are
      discussed in terms of the current literature on social environment and health.

PMID- 7589418
TI  - Integrating qualitative and quantitative research methods: a research model.
AB  - A historical antagonism between proponents of qualitative methods and
      quantitative methods has prevented recognition of the benefits to be gained by
      employing both methods (that is, a multi-method approach) during the same study
      or program of studies. Increasingly, family therapy researchers have begun to
      recognize the value of a multi-method approach in bridging the current gaps among
      theory, research, and practice. However, current writings have yet to move beyond
      the discussion stage. This article proposes a bidirectional continuum that
      includes both qualitative and quantitative methods. An ethnographic content
      analysis approach is presented to illustrate the procedural stages of this
      continuum. The article ends with a discussion of the challenges in carrying out a
      bidirectional, multi-method approach and the potential contributions that an
      integrative research methodology will give both researchers and clinicians.

PMID- 7589419
TI  - An infertility primer for family therapists: I. Medical, social, and
      psychological dimensions.
AB  - A seemingly "self-evident truth" in most people's lives is that one day they will
      have children. This universal, biopsychosocial assumption goes unchallenged until
      a couple faces infertility. Although the effects of such a challenge are
      profound, infertility is often treated as a nonevent--both within our society as
      a whole, and within the field of family therapy in particular. To assist
      clinicians who work with this numerically increasing population, and the many
      others who have been affected by their encounter with infertility in the past,
      this article discusses the biological/medical, psychological, and social factors
      that shape the experience of infertility in our society.

PMID- 7589421
TI  - "Becoming": a method for expanding systemic thinking and deepening empathic
      accuracy.
AB  - The method of "becoming", as an approach to increasing empathic ability,
      promoting exploratory dialogue, and heightening consciousness, is described. The
      method is seen as applicable across theoretical orientations. It is a way to
      operationalize Martin Buber's concept of "inclusion," which he defined as a "bold
      swinging" into the consciousness of another person. Details are given about the
      method's application to resistance, confusion, defensiveness, criticalness, and
      other barriers to awareness, relationship, and the co-creation of shared
      meanings. Case examples are provided to illustrate the use of the method in a
      variety of contexts.

PMID- 7589420
TI  - An infertility primer for family therapists: II. Working with couples who
      struggle with infertility.
AB  - The distress of infertility and its medical treatments are profound, and the
      effects reverberate in each partner, the couple dyad, and the couple's
      relationships with family, friends, and medical systems. Yet family therapists,
      like others in our society, are often uninformed or misinformed about the
      experience of infertility. While the legacies of infertility may be painful and
      enduring, they often remain unspoken, and hence may be overlooked in standard
      interviews. This article describes the experiences of couples struggling with
      infertility, most of whom have sought medical intervention, and it provides
      treatment interventions for guiding couples through this difficult and often
      uncharted terrain. Case vignettes derived from 2 years of this clinical research
      study are included.

PMID- 7589424
TI  - Threading analysis suggests that the obese gene product may be a helical
      cytokine.
AB  - The ob gene encodes a protein that, in mutant form, is associated with obesity
      and type II diabetes in mice. Sequence analysis has revealed no similarities to
      other proteins, however, and no clues as to possible functions. The possibility
      nonetheless remains that ob is functionally or ancestrally related to other
      proteins, whose sequences are divergent to the point that only a comparison of
      three-dimensional structures might detect relationship. To explore this
      possibility, we conduct a 'threading' search of a 3-dimensional structure
      database, to determine whether the ob protein might adopt a fold similar to any
      known structure. This search reveals that the ob sequence is compatible, at a
      significance level of P < 0.05, with structures from the family of helical
      cytokines that includes interleukin-2 and growth hormone. A structural model of
      ob based upon these results is physically and biologically plausible and leads to
      testable predictions, including the prediction that ob may activate the JAK-STAT
      pathway, via binding to a receptor resembling those of the cytokine family.

PMID- 7589422
TI  - Transforming growth factor-beta 1 downregulates dexamethasone-induced tetranectin
      gene expression during the in vitro mineralization of the human osteoblastic cell
      line SV-HFO.
AB  - In the present study, we examined the regulation of tetranectin gene expression
      using a human osteoblastic cell line, SV-HFO, that undergoes mineralization upon
      treatment with dexamethasone. We found that the expression of tetranectin and
      alkaline phosphatase mRNA was induced by dexamethasone treatment as evidenced by
      Northern blotting. When transforming growth factor-beta 1 (TGF-beta 1) was added
      together with dexamethasone to the SV-HFO cell cultures, the mineralization
      process was markedly suppressed and the expression of tetra nectin and alkaline
      phosphatase was downregulated in a dose-dependent manner. These results
      demonstrate that the expression of tetranectin in these osteoblastic cells is
      regulated by dexamethasone and TGF-beta 1 and that tetranectin expression is
      tightly linked to the process of mineralization.

PMID- 7589423
TI  - Crystallization and preliminary X-ray analysis of outer membrane phospholipase A
      from Escherichia coli.
AB  - The outer membrane phospholipase A (OMPLA) of Escherichia coli is one of the few
      integral outer membrane proteins displaying enzymatic activity. It is encoded as
      a mature protein of 269 amino acids preceded by a signal sequence of 20 amino
      acids. There is no sequence homology with water-soluble lipases and
      phospholipases. Crystals of the mature enzyme were obtained at 22 degrees C from
      24-28% (v/v) 2-methyl-2,4-pentanediol in Bis-Tris buffer, pH 5.9-6.0, with 1 mM
      calcium chloride and 1.5% (w/v) beta-octylglucoside. They have the symmetry of
      the trigonal spacegroup P3(1)21 (or P3(2)21) with cell dimensions of a = b = 79.6
      A and c = 102.8 A (alpha = beta = 90 degrees, gamma = 120 degrees). Native
      crystals diffract to a resolution of 2.6 A.

PMID- 7589425
TI  - Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in
      Madin-Darby canine kidney cells.
AB  - We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of
      pancreatitis-associated ascitic fluid (PAAF) collected from rats with
      experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a
      time- and dose-dependent manner. We detected DNA fragmentation on the PAAF
      treated MDCK cells, indicating that the cytocidal action of PAAF is via
      apoptosis. From the results obtained, we conclude that PAAF contains factor(s)
      inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is
      involved in the mechanism of organ failure in acute pancreatitis.

PMID- 7589427
TI  - Basal dephosphorylation controls slow gating of L-type Ca2+ channels in human
      vascular smooth muscle.
AB  - The role of cellular phosphatase activity in regulation of smooth muscle L-type
      Ca2+ channels was investigated using tautomycin, a potent and specific inhibitor
      of serin/threonin phosphatases type 1 and 2A. Tautomycin (1-100 nM) inhibited
      Ca2+ channel activity in smooth muscle cells isolated from human umbilical vein.
      Tautomycin-induced inhibition of Ca2+ channel activity was due to a reduction of
      channel availability which originated mainly from prolongation of the lifetime of
      unavailable states of the channel. Pretreatment of smooth muscle cells with the
      protein kinase inhibitor H-7 (10 microM) prevented the inhibitory effect of
      tautomycin. Our results suggest modulation of slow gating between available and
      unavailable states as a mechanism of phosphorylation-dependent down-regulation of
      Ca2+ channels in vascular smooth muscle.

PMID- 7589429
TI  - Crystals of soluble interleukin-1 receptor complexed with its natural antagonist
      reveal a 1:1 receptor-ligand complex.
AB  - Interleukin-1 is a cytokine involved in the acute phase response against
      infection and injury. We obtained crystals of a complex of soluble, recombinant
      human interleukin-1 receptor and recombinant human interleukin-1 receptor
      antagonist, a naturally occurring antagonist. The crystals are suitable for X-ray
      analysis and diffract to 2.7 A resolution. Solvent content calculations indicate
      that the crystals contain one receptor and one antagonist molecule per asymmetric
      unit. Other receptor to antagonist ratios are highly unlikely. These results
      suggest that the interleukin-1 antagonist binds a single receptor molecule and
      does not cause receptor aggregation.

PMID- 7589428
TI  - Effect of hypoosmolality on the abundance, poly(A) tail length and axonal
      targeting of arginine vasopressin and oxytocin mRNAs in rat hypothalamic
      magnocellular neurons.
AB  - Arginine vasopressin (AVP) and oxytocin (OT) mRNAs are targeted to the axonal
      compartment of rat hypothalamic magnocellular neurons. Salt-loading results in a
      considerable rise in hypothalamic and axonal AVP mRNA but only a moderate
      increase for axonal OT mRNA. Here we report that hypoosmolality gives rise to a
      rapid decrease of axonal AVP encoding transcripts to undetectable levels after 2
      weeks. The levels of OT mRNA in the axonal compartment did not change
      significantly. In the hypothalamus the mRNA for AVP also decreased. The size of
      the poly(A) tract of AVP encoding transcripts appeared to be strictly correlated
      with plasma osmolality. In contrast, the amount and size of OT encoding mRNAs
      were only moderately or not influenced by hypoosmolar stimuli.

PMID- 7589426
TI  - Molecular cloning, functional expression, and signal transduction of the GIP
      receptor cloned from a human insulinoma.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the
      regulation of postprandial insulin secretion and proinsulin gene expression of
      pancreatic beta-cells. This study demonstrates the molecular cloning of a cDNA
      for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. The cloned
      cDNA encoded a seven transmembrane domain protein of 466 amino acids which showed
      high homology (41%) to the human glucagon-like peptide 1 (GLP-1) receptor.
      Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively.
      When transfected stably into fibroblast CHL-cells a high affinity receptor was
      expressed which coupled to the adenylate cyclase with normal basal cAMP and
      increasing intracellular cAMP levels under stimulation with human GIP-1-42 (EC50
      = 1.29 x 10(-13) M). The receptor accepted only human GIP 1-42 (Kd = 1.93 +/- 0.2
      x 10(-8) M) and porcine truncated GIP 1-30 (Kd = 1.13 +/- 0.1 x 10(-8) M) as high
      affinity ligands. At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP
      binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive
      intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl
      cyclase activating peptide were without effect. In transfected CHL cells, GIP-1
      42 did not increase intracellular calcium. Northern analysis revealed one
      transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. The exact
      understanding of GIP receptor regulation and signal transduction will aid in the
      understanding of the incretin hormone's failure to exert its biological action at
      the pancreatic B-cell in type II diabetes mellitus.

PMID- 7589430
TI  - The cytostatic activity of 5-(1-azidovinyl)-2'-deoxyuridine (AzVDU) against
      herpes simplex virus thymidine kinase gene-transfected FM3A cells is due to
      inhibition of thymidylate synthase and enhanced by UV light (lambda = 254 nm)
      exposure.
AB  - 5-(1-Azidovinyl)-2'-deoxyuridine (AzVDU) and a series of 5-[1-azido-2
      halogenoethyl]-derivatives of beta-D-arabinofuranosyluracil (AU) proved markedly
      inhibitory to the replication of herpes simplex virus type 1 (HSV-1) and
      varicella zoster virus (VZV), but not thymidine kinase (TK)-deficient HSV-1 and
      VZV strains. None of the compounds were cytostatic. However, AzVDU, but not the 5
      [1-azido-2-halogenoethyl]-AU derivatives became highly cytostatic against HSV-1
      and HSV-2 TK gene-transfected FM3A tumor cells. The molecular target for the
      cytostatic effect of AzVDU proved to be thymidylate synthase. Short exposure of
      AzVDU-treated FM3A TK-/HSV-1 TK+ cells to irradiation at lambda = 254 nm enhanced
      the cytostatic activity of AzVDU by 5-fold.

PMID- 7589431
TI  - Identification of the human mitochondrial protein import receptor, huMas20p.
      Complementation of delta mas20 in yeast.
AB  - The human homolog of the S. cerevisiaelN. crassa mitochondrial protein import
      receptor, Mas20p/MOM19, has been identified and characterized. Sequence
      similarities between these three proteins is most pronounced within the NH2
      terminal third of the molecules. However, the mammalian protein exhibits only
      weak homology to the tetratricopeptide repeat B domain that is found in
      Mas20p/MOM19. huMas20p is targeted and inserted into the outer membrane of
      isolated rat heart mitochondria, in the Nin-Ccyto orientation. Antibodies
      directed against the soluble portion of huMas20p inhibited in vitro mitochondrial
      import of a diverse set of precursor proteins (including inner membrane
      uncoupling protein), but failed to block import of a fusion protein bearing the
      signal-anchor sequence of Mas20p itself. Finally, expression of huMAS20
      complemented the respiratory defect of delta mas20 yeast cells. Together, these
      results demonstrate that huMAS20p is a component of the mammalian import
      apparatus.

PMID- 7589432
TI  - Cloning and sequencing of a human thioredoxin reductase.
AB  - The DNA sequence encoding human placental thioredoxin reductase has been
      determined. Of the 3826 base pairs sequenced, 1650 base pairs were in an open
      reading frame encoding a mature protein with 495 amino acids and a calculated
      molecular mass of 54,171. Sequence analysis showed strong similarity to
      glutathione reductases and other NADPH-dependent reductases. Human thioredoxin
      reductase contains the redox-active cysteines in the putative FAD binding domain
      and has a dimer interface domain not previously seen with prokaryote and lower
      eukaryote thioredoxin reductases.

PMID- 7589433
TI  - Interaction of p85 subunit of PI 3-kinase with insulin and IGF-1 receptors
      analysed by using the two-hybrid system.
AB  - Interaction of the p85 subunit of PI 3-kinase with the insulin receptor (IR) and
      the IGF-1 receptor (IGF-1R) was investigated using the two-hybrid system by
      assessing for his3 and lacZ activation in S. cerevisiae. The experiments were
      performed with the cytoplasmic beta domain (wild type or mutated) of IR and IGF
      1R and p85 or its subdomains (N + C-SH2, N-SH2, C-SH2, SH3 + N-SH2). The results
      of his3 activation indicated that p85, N + C-SH2 and C-SH2 interact with both IR
      beta and IGF-1R beta, whereas N-SH2 and SH3 + N-SH2 interact only with IR beta.
      Interaction of p85 and N+C-SH2 with IR beta (delta C-43) or IGF-1R beta(delta C
      43) in which the C-terminal 43 amino acids (including the YXXM motif) were
      deleted, persisted. The internal binding site thus revealed was not altered by
      further mutating Y960/F for IR or Y950/F for IGF-1R. Activation of lacZ upon
      interaction of p85 with IR beta(delta C-43) was 4-fold less as compared to IR
      beta. This activation with p85 and IGF-1R beta was 4-fold less as compared to IR
      beta and was somewhat increased (2-fold) for IGF-1R beta (delta C-43). Thus, the
      C-terminal domain in IGF-1R appears to exert a negative control on binding of p85
      thereby providing a possible regulatory mechanism for direct activation of the PI
      3-kinase pathway.

PMID- 7589435
TI  - Identification of a novel human serpin gene; cloning sequencing and expression of
      leupin.
AB  - A novel serpin gene has been isolated, cloned and sequenced. A PCR amplified
      fragment of the gene was originally identified from human genomic DNA, and the
      full-length cDNA was subsequently isolated from HeLa cells and sequenced. The
      novel serpin is very high in protein sequence similarity (91.8%) to the squamous
      cell carcinoma antigen (SCCA), but contains substantial differences in the
      reactive site loop sequence, including a different amino acid (leucine) in the P1
      position. The gene product, named leupin, is expressed in HeLa cells, SKGIIIa
      cells and human placenta. The protein has a predicted M(r) of 44,857 and an
      isoelectric point of 6.04 which is consistent with the more acidic form of SCCA
      associated with squamous cell carcinomas.

PMID- 7589434
TI  - RNA editing in wheat mitochondria proceeds by a deamination mechanism.
AB  - Most if not all mitochondrial messenger RNAs from seed plants undergo a post
      transcriptional modification (RNA editing) involving the conversion of some
      cytidine residues to uridine. Using a molecular hybridization approach, an in
      vitro RNA editing system, able to faithfully reproduce the in vivo observed C to
      U changes of subunit 9 (atp9) of wheat mitochondrial ATP synthase mRNA, has been
      described [Araya et al. (1992) Proc. Natl. Acad. Sci. USA 89, 1040-1044]. In this
      work we extend these studies to better understand the biochemical mechanism of
      this process. RNA editing was analysed by P1 nuclease digestion of the reaction
      product followed by thin layer chromatography. Experiments performed with
      unedited [3H]RNA labelled on the base and with unedited [32P]RNA labelled at the
      alpha-phosphate of cytidine residues, indicate that plant mitochondrial RNA
      editing operates through a deamination mechanism.

PMID- 7589436
TI  - Mutations in RCA1 and AFG3 inhibit F1-ATPase assembly in Saccharomyces
      cerevisiae.
AB  - The RCA1 (YTA12) and AFG3 (YTA10) genes of Saccharomyces cerevisiae code for
      homologous mitochondrial proteins that belong to the recently described AAA
      protein-family [Kunau et al. (1993) Biochimie 75,209-224]. Mutations in either
      gene have been shown to induce a respiratory defect. In the case of rca1 mutants
      this phenotype has been ascribed to defective assembly of cytochrome oxidase and
      ubiquinol-cytochrome c reductase. In the present study we show that the
      respiratory defect of afg3 mutants, like that of rca1 mutants, is also caused by
      an arrest in assembly of cytochrome oxidase and ubiquinol-cytochrome c reductase.
      In addition to the absence of the respiratory complexes, rca1 and afg3 mutants
      exhibit reduced mitochondrial ATPase activity. As a first step to an
      understanding of the biochemical basis for the ATPase defect we have examined the
      assembly of the F1 and F0 constituents of the ATPase complex. We present evidence
      that the ATPase lesion stems at least in part from the failure of rca1 and afg3
      mutants to assemble F1. Although the mutants also display lower steady-state
      concentrations of some F0 subunits, this could be a secondary effect of defective
      F1 assembly.

PMID- 7589437
TI  - The cardiac sarcoplasmic reticulum phospholamban kinase is a distinct delta-CaM
      kinase isozyme.
AB  - Phospholamban is the regulator of the Ca(2+)-ATPase in cardiac sarcoplasmic
      reticulum (SR). It is phosphorylated by a Ca2+/calmodulin-dependent protein
      kinase (SRCaM kinase) which is closely associated with cardiac SR membrane
      preparations. We found that, upon renaturation of pig cardiac SR proteins,
      blotted onto PVDF membrane, two polypeptides of 54 and 52 kDa showed
      Ca2+/calmodulin-dependent autophosphorylation. In Western blots of SR proteins,
      the 54/52 kDa polypeptides were recognized by an antibody specific for the delta
      CaM kinase isoforms, but not by an anti-alpha-CaM kinase. The two polypeptides
      were selectively immunoprecipitated from solubilized SR vesicles with the anti
      delta-CaM kinase. The CaM kinase inhibitors KN-62 and peptide CaMK-(281-302)
      inhibited the activity of the SRCaM kinase with IC50 values in the same range
      with those obtained for the brain isozyme. In addition, initial
      autophosphorylation (Ca(2+)-dependent) produced a partially Ca(2+)-independent
      enzyme while further autophosphorylation (Ca(2+)-independent) made the enzyme
      completely Ca(2+)-independent. Based on these results we suggest that the SRCaM
      kinase is a distinct delta-CaM kinase isozyme.

PMID- 7589439
TI  - Time-resolved surface charge change on the cytoplasmic side of bacteriorhodopsin.
AB  - The pH-sensitive dye 5-iodoacetamidofluorescein was covalently bound to a single
      cysteine residue introduced by site-directed mutagenesis in position 101 on the
      cytoplasmic surface or in position 130 on the extracellular surface of the proton
      pump bacteriorhodopsin. Using time-resolved absorption spectroscopy at 495 nm a
      transient increase was observed in the apparent pK of the dye attached at residue
      101. At pH 7.3 the rise and decay times of this pK-change (approximately 2 ms and
      approximately 60 ms) correlate well with decay times observed for the M and O
      intermediates and with the proton uptake time. Interpreting the pK-increase of
      +0.18 pH-unit in terms of a transiently more negative surface charge density, we
      calculate a change of -0.80 elementary charge per bacteriorhodopsin at the
      cytoplasmic surface. It is likely that this charge change is due to the transient
      deprotonation of aspartate-96. With the label in position 130 on the
      extracellular surface no transient pK-shift was detected.

PMID- 7589438
TI  - Localisation of metallothionein isoform mRNAs in rat hepatoma (H4) cells.
AB  - The localisation of metallothionein isoform mRNAs in rat hepatoma (H4) cells was
      investigated using two approaches, namely Northern hybridisation of total RNA
      extracted from free, cytoskeletal-bound and membrane-bound polysomes isolated by
      a sequential detergent/salt extraction procedure and in situ hybridisation. The
      cytoskeletal-bound polysomes were enriched in metallothionein-I (MT-I) and c-myc
      mRNAs but showed a significantly lower enrichment in MT-II mRNA. These findings
      indicate that the MT-I mRNA is localised to the cytoskeleton during translation.
      In situ hybridisation using a biotin-labelled oligonucleotide probe revealed a
      predominantly perinuclear localisation for the MT-I mRNA.

PMID- 7589440
TI  - Human pancreatic phospholipase A2 stimulates the growth of human pancreatic
      cancer cell line.
AB  - Phospholipase A2 (PLA2) from human pancreas, designated hPLA2-I, functions as a
      digestive enzyme. Interestingly, the present study demonstrated that the mature
      form of hPLA2-I stimulated the growth of a human pancreatic cancer cell line
      MIAPaCa-2, whereas the pro-form was ineffective. PLA2s from Laticauda
      semifasciata fraction I, Crotalus adamanteus venom, Streptomyces violaceoruber
      and bee venom, showed no proliferative effect to the growth of MIAPaCa-2. The
      Scatchard plot analysis revealed that the MIAPaCa-2 cell had a specific binding
      site for the mature hPLA2-I. The equilibrium binding constant (Kd) and the
      maximum binding capacity (Bmax) were 2.6 nM and 0.4 fmol/10(6) cells,
      respectively. These results suggest that the mature hPLA2-I, but not the pro
      form, may function as a growth factor of pancreas carcinoma via the specific
      binding site.

PMID- 7589441
TI  - Biochemical complementation studies in vitro of gyrase subunits from different
      species.
AB  - To investigate the functional equivalence of DNA gyrase subunits from different
      bacterial sources hybrid enzymes were formed using purified A and B subunits from
      three species of Streptomycetes, E. coli and B. subtilis. The activity of gyrase
      hybrids composed of heterologous gyr A and gyr B proteins and of the gyrases
      containing homologous subunits was characterized by binding studies and a
      cleavage assay with two different DNA fragments. Likewise the enzyme activity was
      monitored by the super-coiling and relaxation assay with pBR322 DNA. We found
      that cleavage reactions are largely determined by the source of the gyr B
      subunits whereas DNA supercoiling and relaxation reactions of pBR322 catalyzed by
      DNA gyrase are limited to a combination of homologous A and B subunits or of
      heterologous A and B subunits from the taxonomically related bacteria
      Streptomycetes.

PMID- 7589442
TI  - Alternative splicing of AMPA receptor subunits: regulation in clonal cell lines.
AB  - Alternative splicing of AMPA receptors was investigated in rat PC12 and human SH
      SY5Y cells. PC12 cells predominantly expressed GluR-B flip mRNA before and after
      differentiation. In SH-SY5Y cells, each AMPA-receptor subunit showed a distinct
      splice variant expression profile throughout differentiation. GluR-B mRNA was
      comparable in expression levels for flip and flop splice variants. In the other
      AMPA-receptor subunit transcripts the flip form was the more prominent splice
      variant. After three days post induction a transient elevation of GluR-B and -D
      flop mRNA expression could be observed.

PMID- 7589444
TI  - The block of the expressed L-type calcium channel is modulated by the beta 3
      subunit.
AB  - The alpha 1C subunit of the L-type calcium channel was stable, expressed alone or
      in combination with the beta 3 subunit in Chinese hamster ovary cells. The beta 3
      subunit enhanced significantly the inactivation of barium currents indicating
      that both subunits interacted with each other. The beta 3 subunit decreased
      significantly the half-maximal inhibitory concentration of the calcium channel
      blockers (-)-gallopamil and verapamil, but did not affect significantly the block
      caused by isradipine and mibefradil at the holding potentials of -80 mV and -40
      mV. These results suggest that the beta 3 subunit affects distinctly the
      interaction of the expressed alpha 1C subunit with different classes of organic
      calcium channel blockers.

PMID- 7589445
TI  - Shear stress induces expression of CNP gene in human endothelial cells.
AB  - To elucidate the effect of blood flow on gene transcription of C-type natriuretic
      peptide (CNP), human umbilical vein endothelial cells were exposed to shear
      stress in a cone-plate viscometer. Expression of CNP mRNA, evaluated by reverse
      transcription-polymerase chain reaction, was markedly increased by exposure to
      shear stress of 24 dyne/cm2 at 3 h. The CNP mRNA level was maintained until 12 h.
      Thus, the present study demonstrated for the first time that shear stress induces
      expression of CNP gene in human endothelial cells.

PMID- 7589443
TI  - Binding of endothelin to plasma proteins and tissue receptors: effects on
      endothelin determination, vasoactivity, and tissue kinetics.
AB  - In vitro binding of (3-[125I]Tyr)-endothelin-1 ([125I]ET-1) and (3-[125I]Tyr)-big
      ET-1(1-38) ([125I]big ET-1) to plasma proteins of healthy humans, cardiac
      patients and normotensive and hypertensive rats was investigated by equilibrium
      dialysis. Binding of both tracers was similar in plasma from healthy humans,
      patients with congestive heart failure, and following myocardial infarction
      (approximately 60%), and marginally higher in rat plasmas (approximately 70%).
      Binding of [125I]ET-1 to human plasma could be explained by binding to human
      serum albumin. Endogenous plasma ET-1 levels were approximately 9 pg/ml in
      healthy humans, and approximately 12-16 pg/ml in cardiac patients; big ET-1
      concentrations were approximately two- to threefold higher. ET-1 bound to plasma
      protein was partly lost in column extraction. In rat isolated perfused hearts,
      the coronary dilator and constrictor potency of exogenous free and albumin-bound
      ET-1 was similar, whereas the kinetics of endogenous ET-1 was impeded by tight
      binding to ET receptors. The data indicate that binding of ET-1 to plasma
      proteins is without effect on peptide vasoactivity, but binding to tissue
      receptors greatly impedes its tissue kinetics.

PMID- 7589446
TI  - The pyruvate dehydrogenase complex of Saccharomyces cerevisiae is regulated by
      phosphorylation.
AB  - Mitochondria were isolated from Saccharomyces cerevisiae grown on different
      carbon sources prior to incubation with [gamma-32P]ATP. A major 46,000-M(r)
      phosphoprotein, corresponding in M(r) value to the E1 alpha subunit of the yeast
      pyruvate dehydrogenase complex (PDC), was detected only in mitochondria isolated
      from cells grown on a fermentable carbon source such as galactose.
      Immunoprecipitation with subunit-specific antiserum to the E1 component of
      mammalian or yeast PDC confirmed the identity of this polypeptide. PDC activity
      in isolated yeast mitochondria could be inactivated in an ATP-dependent fashion
      and reactivated in the presence of Ca2+ ions.

PMID- 7589447
TI  - Differential up-regulation by tRNAs of ribosome-inactivating proteins.
AB  - Some plant ribosome-inactivating proteins (RIPs) with RNA-N-glycosidase activity
      on 28S RNA require, for the inactivation of ribosomes, the presence of
      macromolecular cofactors present in post-ribosomal supernatants. In the case of
      gelonin one of the cofactors is tRNATrp lacking one or two nucleotides at the 3'
      CCA end [Brigotti, M., Carnicelli, D., Alvergna, P., Pallanca, A., Lorenzetti,
      R., Denaro, M., Sperti, S. and Montanaro, L. (1995) Biochem. J. 310, 249-253]. In
      the present study it is shown that tRNAs are involved in the up-regulation of all
      the cofactor-requiring RIPs up to now identified (agrostin, barley RIP, PAP and
      tritin, besides gelonin). Polyacrylamide gel electrophoresis shows that tRNA
      fractions with different mobilities stimulate different RIPs. With the
      identification of agrostin, the cofactor-requiring RIPs (italics) add to five out
      of a total of thirteen investigated: barley RIP, bryodin-R, gelonin, lychnin,
      momordin, momorcochin-S, PAP, saporin-6, tritin [Carnicelli, D., Brigotti, M.,
      Montanaro, L. and Sperti, S. (1992) Biochem. Biophys. Res. Commun. 182, 579-582],
      agrostin, luffin, trichokirin and trichosanthin (present study).

PMID- 7589448
TI  - A developmentally regulated member of the sialyltransferase family (ST8Sia II,
      STX) is a polysialic acid synthase.
AB  - We found polysialic acid synthase activity of ST8Sia II (STX) in vitro and in
      vivo. Previously, we showed that mouse ST8Sia II exhibits alpha 2,3-sialylated N
      glycan alpha 2,8-sialyltransferase activity, but the polysialic acid synthase
      activity of ST8Sia II was not detected at that time [Kojima, N. et al. (1995)
      FEBS Lett. 360, 1-4]. When fetuin was [14C]sialylated with ST8Sia II and then its
      N-linked oligosaccharides were analyzed, a part of the N-linked oligosaccharides
      was eluted in the void volume from a Sephadex G-50 column, and was eluted in the
      void volume from a Sephadex G-50 column, and was eluted from the DEAE-Toyopearl
      column at almost the same salt concentration as that where colomic acid was
      eluted. In addition, a series of 14C-labeled oligo-sialic acids were obtained
      from the oligosaccharides on partial mild acid hydrolysis. These results
      indicated that a part of N-linked oligosaccharides of fetuin were polysialylated
      with ST8Sia II. Transfection of ST8Sia II gene into several cell lines including
      NIH3T3 led to the expression of polysialic acids on the cell surface. Thus,
      ST8Sia II can directly synthesize polysialic acid chains on alpha 2,3-sialylated
      N-linked oligosaccharides of glycoproteins without any initiator
      sialytransferase.

PMID- 7589450
TI  - Voltage-gated K+ currents of mouse dendritic cells.
AB  - Dendritic cells (DC) were enriched from murine spleen by exploring their
      intermediate density and transient weak adherence. The isolated population
      contained excellent antigen presenting cells with high surface expression of
      major histocompatibility complex (MHC) class II determinants thus exhibiting
      crucial immunofunctional characteristics of DC. Cells of typical dendritic shape
      were electrophysiologically analysed using the whole cell configuration of the
      patch clamp technique. All 26 cells expressed only outward K+ currents comparable
      to those detected in cytokine-activated microglia. Co-purified splenic
      macrophages, in contrast, displayed an inward rectifying K+ current.

PMID- 7589449
TI  - Phosphatase toward MAP kinase is regulated by osmolarity in Madin-Darby canine
      kidney (MDCK) cells.
AB  - We have reported that MAP kinase and its activator were activated by increase in
      extracellular osmolarity in Madin-Darby canine kidney (MDCK) cells [J. Clin.
      Invest. 93 (1994) 2387-2392]. The activation of MAP kinase quickly disappeared
      when cells in hypertonicity were shifted to isotonicity. Present study was
      planned to elucidate the mechanism for the inactivation of MAP kinase when
      osmolarity decreased. Combination of two different phosphatase inhibitors, 10(-6)
      M okadaic acid and 0.2 mM sodium orthovanadate, blocked the inactivation of MAP
      kinase after the decrease in osmolarity. We also demonstrated that phosphatase
      toward MAP kinase was activated in response to the decrease in osmolarity. These
      results suggest that MAP kinase is inactivated by phosphatase that is activated
      when osmolarity decreased.

PMID- 7589451
TI  - Modulation of obese gene expression in rat brown and white adipose tissues.
AB  - The ob gene mRNA expression in rat brown adipose tissue (BAT) and epididymal
      white adipose tissue (WAT) was measured on Northern blots hybridized with a rat
      ob gene probe. The level of ob gene mRNA in BAT was about 40% of that in WAT.
      Fasting (36 h) or semi-starvation (10 days) decreased the ob gene mRNA level in
      both tissues by 62-68%, and cold exposure at 6 degrees C (24 h) decreased it in
      BAT (-84%) but not in WAT. Acute administration of the beta 3-adrenergic agonist
      Ro 16-8714 decreased the ob gene mRNA level in BAT (-51%) and WAT (-28%) of lean
      Zucker rats and only in BAT (-74%) of obese falfa rats. This study demonstrates
      that, in the rat, the ob gene is not only expressed in WAT but also in BAT, and
      suggests that in these two tissues, the modulation of the ob gene expression
      might be more closely associated with known alterations in cell lipid content
      than with changes in sympathetic activity.

PMID- 7589452
TI  - Possible role of protein kinase C in the regulation of intracellular stability of
      focal adhesion kinase in mouse 3T3 cells.
AB  - Effects of various types of protein kinase inhibitor on the adhesion and
      spreading of BALB/c mouse 3T3 cells and on the phosphorylation and stability of
      focal adhesion kinase (FAK) in the cells were studied. Inhibitors of protein
      tyrosine kinases, methyl 2,5-dihydroxycinnamate and herbimycin A, inhibited
      tyrosine-phosphorylation of FAK and the adhesion of 3T3 cells to fibronectin.
      Among inhibitors of serine/threonine kinases tested, calphostin C, a specific
      inhibitor of protein kinase C, inhibited cell spreading rather than cell
      adhesion, and it induced the decrease of intracellular FAK within 30 min.
      Inhibitors of tyrosine kinase, A kinase, G kinase, and myosin light chain kinase
      did not induce such a rapid and specific decrease of FAK. When calphostin C (20
      microM) was added to sub-confluent monolayer cultures, serine-phosphorylation of
      FAK was inhibited by 67% within 2 h, and decrease in the amount of FAK and
      rounding up of the cells began after 4 h. Label-chase experiments indicated that
      about 60% of 35S-labeled FAK degraded within 1-2 h after addition of calphostin C
      to monolayer cultures. These results indicated that serine-phosphorylation of FAK
      induced by protein kinase C was important in the regulation of metabolic
      stability of FAK.

PMID- 7589453
TI  - Influence of ADP, AMP-PNP and of depletion of nucleotides on the structural
      properties of F1ATPase: a Fourier transform infrared spectroscopic study.
AB  - Mitochondrial F1ATPase from beef heart was treated with different buffers in
      order to modulate the nucleotide content of the enzyme and then analysed by FT-IR
      spectroscopy. Treatment of F1ATPase with a buffer lacking nucleotides and
      glycerol led to the formation of two fractions consisting of an inactive
      aggregated enzyme deprived almost completely of bound nucleotides and of an
      active enzyme containing ATP only in the tight sites and having a structure
      largely accessible to the solvent and a low thermal stability. Treatment of
      F1ATPase with saturating ADP, which induced the hysteretic inhibition during
      turnover, or AMP-PNP did not affect remarkably the secondary structure of the
      enzyme complex but significantly increased its compactness and thermal stability.
      It was hypothesised that the formation of the inactive aggregated enzyme was
      mainly due to the destabilisation of the alpha-subunits of F1ATPase and that the
      induction of the hysteretic inhibition is related to a particular conformation of
      the enzyme, which during turnover becomes unable to sustain catalysis.

PMID- 7589455
TI  - In vivo treatment of Heymann's Nephritis using a cytotoxic protein-toxin
      conjugate.
AB  - In this study we investigated the possibility of treating Heymann's Nephritis
      (HN) by destroying antibody producing cells by targetting a toxin, gelonin-
      conjugated to gp330, the renal brush border antigen. HN was induced in rats by
      immunizing them with purified gp330. The gelonin-gp330 conjugate was administered
      12 days after the antigenic challenge. Serum was screened for circulating
      antibodies. Proteinurea was estimated. The gp330-gelonin conjugate-treated
      animals had a circulating antibody titre in the serum much lower than that of
      diseased (untreated) animals. Proteinurea seen in diseased animals was not
      observed in treated animals. This work suggests the possibility of using a toxin
      antigen conjugate for immunomodulating antibody mediated autoimmune renal
      disease.

PMID- 7589454
TI  - PKC alpha regulates thrombin-induced PDGF-B chain gene expression in mesangial
      cells.
AB  - Thrombin is a potent mitogen for mesangial cells and stimulates PDGF B-chain gene
      expression in these cells. It also activates phospholipase C (PLC) resulting in
      an increase in cytosolic Ca2+ and diacylglycerol (DAG) that are the physiological
      activators of protein kinase C (PKC). Immunoprecipitation of specific PKC
      isotypes from thrombin-stimulated mesangial cells with subsequent measurement of
      their enzymatic activity shows activation of Ca(2+)-dependent PKC alpha and
      Ca(2+)-independent PKC zeta in a time dependent manner. Optimum activation of
      both of these isozymes was obtained at 60 minutes. PKC alpha activity increased
      83% over basal while activity of PKC zeta increased 104%. Prolonged exposure of
      mesangial cells to phorbol myristate acetic acid (PMA) inhibited the enzymatic
      activity of PKC alpha but not PKC zeta. This inhibition of PKC alpha had no
      effect on thrombin-induced DNA synthesis but abolished PDGF B-chain gene
      expression induced by thrombin. These data provide the first evidence that PKC
      alpha activation is necessary for thrombin-induced PDGF B-chain gene expression
      but not for thrombin-induced DNA synthesis.

PMID- 7589457
TI  - Characterization and functional dissection of the galectin-1 gene promoter.
AB  - The galectin-1 gene encodes a beta-galactoside-binding protein whose
      overexpression is associated with neoplastic transformation and loss of
      differentiation. Transient transfection assays of a series of deletions
      constructs (pGAT) showed that the galectin-1 promoter is highly active in cells
      both expressing and non-expressing the endogenous gene, and that the basal
      activity is determined by sequences encompassing the transcription start site (
      50/+50). Both an upstream (-50/-26) and a downstream position-dependent (+10/+50)
      cis-elements are necessary for efficient transcriptional activity and are able to
      bind nuclear proteins.

PMID- 7589458
TI  - Expression of the cyclin-dependent kinase inhibitor p16 during the ongoing cell
      cycle.
AB  - It has been demonstrated that protein expression of p16, the inhibitor of cyclin
      dependent kinase 4 and 6, increases 4 fold at the G1/S transition when serum
      arrested cells are restimulated to logarithmic growth. We examined the cell cycle
      regulation of this cyclin-dependent kinase inhibitor in cells separated according
      to their cell cycle phases by centrifugal elutriation. Neither p16 mRNA nor its
      protein expression are regulated during the cell cycle of normal
      phytohemagglutinin-stimulated lymphocytes, retinoblastoma protein-negative cells,
      papilloma virus-transformed cells, and acute promyelocytic leukemia cells. p16
      mRNA is constitutively expressed in cells in which we detected the normal E2F
      dependent S-phase specific expression of thymidine kinase mRNA. We further
      observed a G1-phase specific expression of cyclin D1 mRNA in the same cells
      separated by centrifugal elutriation.

PMID- 7589456
TI  - Interaction of the protein nucleobindin with G alpha i2, as revealed by the yeast
      two-hybrid system.
AB  - The heterotrimeric G protein, G alpha i2, transduces signals from seven membrane
      spanning receptors to effectors such as adenylyl cyclase and ion channels. The
      purpose of this study was to identify these or other cellular proteins that
      interact with G alpha i2 by use of the yeast two-hybrid system. A human B cell
      cDNA library was screened by this system using full length G alpha i2. Four
      positive colonies were obtained. Two of the four were identified as nucleobindin,
      a calcium binding protein and a putative antigen to which anti-nuclear antibodies
      are generated in mice with a disorder that resembles systemic lupus
      erythematosus. Nucleobindin has a leucine zipper, EF hands, and a signal peptide
      sequence and is thought to localize to the nucleus as well as being secreted. The
      specificity of intehraction between G alpha i2 and nucleobindin was confirmed by
      an in vitro binding assay using recombinant proteins. Transfection of G alpha i2
      and nucleobindin in COS cells increased G alpha i2 expression relative to cells
      transfected with G alpha i2 and mock vector. Our results indicate that the yeast
      two-hybrid system provides a means to identify novel proteins that interact with
      G alpha proteins. Nucleobindin appears to represent one of those proteins.

PMID- 7589462
TI  - Is there evidence for a cGMP-gated cation channel in the photosensory membrane of
      Sepia? Re publication: 'Evidence for a cGMP gated cation channel in photoreceptor
      cell membranes of Sepia officinalis'.

PMID- 7589459
TI  - YKC1 encodes the depolarization-activated K+ channel in the plasma membrane of
      yeast.
AB  - Our previous patch-clamp studies showed that depolarization activates a K(+)
      specific current in the plasma membrane of the budding yeast, Saccharomyces
      cerevisiae [Gustin et al. (1986) Science 233, 1195-1197]. The Yeast Genome
      Sequencing Project has now uncovered on the left arm of chromosome X an open
      reading frame (ORF) that predicts a 77-kDa protein reminiscent of a shaker-like
      alpha subunit with 6 membrane spans followed by a subunit with 2 spans. We found
      that deleting this ORF removes the yeast K+ current. Furnishing the ORF from
      plasmids restores or even greatly amplifies this current. These manipulations
      have no effects on the 40-pS mechanosensitive conductance also native to this
      membrane. Thus, this ORF, named YKC1 here, likely encodes a structure for the
      K(+)-specific channel of the yeast plasma membrane. This and other K+ channel
      subunits are compared and the possible uses of this gene in research are
      discussed. YKC1 has recently been shown by others to induce in frog oocytes a K+
      current. Its activation is coupled to EK+ and its outward rectification depends
      on external divalent cations. We found the YKC1 channel in its native membrane
      activates at low voltages largely independent of EK+ and it remains so despite
      removal of divalents by chelation.

PMID- 7589460
TI  - Identification of the amino acid residues involved in selective agonist binding
      in the first extracellular loop of the delta- and mu-opioid receptors.
AB  - Effects of amino acid substitutions in the first extracellular loop region of the
      delta- and mu-opioid receptors were examined. Substitution of lysine-108 of the
      delta-receptor (delta K108) with asparagine improved affinity to [D
      Ala2,MePhe4,Gly-ol5]enk ephalin (DAGO), a mu-selective peptide agonist, to be
      comparable with that of the mu-receptor. On the other hand, replacement of mN127
      with lysine decreased the affinity to DAGO by approximately 15-fold. These
      results suggest that dK108 and mN127, which correspond to each other in the
      aligned amino acid sequences, mainly determine the difference in DAGO binding
      affinity between the delta- and mu-receptors.

PMID- 7589461
TI  - Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293
      cells induces cAMP-dependent activation of calcium-induced calcium release.
AB  - The actions of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) on cellular
      signalling were studied in human embryonal kidney 293 (HEK 293) cells stably
      transfected with the cloned human GLP-1 receptor. The cloned GLP-1 receptor
      showed a single high-affinity binding site (Kd = 0.76 nM). Binding of GLP-1(7
      36)amide stimulated cAMP production in a dose-dependent manner (EC50 = 0.015 nM)
      and caused an increase in the intracellular free Ca2+ concentration ([Ca2+]i).
      The latter effect reflected Ca(2+)-induced Ca2+ release and was suppressed by
      ryanodine. We propose that the ability of GLP-1(7-36)amide to increase [Ca2+]i
      results from sensitization of the ryanodine receptors by a protein kinase A
      dependent mechanism.

PMID- 7589463
TI  - Effect of iC3b binding to immune complexes upon the phagocytic response of human
      neutrophils: synergistic functions between Fc gamma R and CR3.
AB  - We compared the phagocytosis of immune complexes (IC) and iC3b-opsonized
      derivatives (iC3b-IC) by human neutrophils. The phagocytosis of iC3b-IC via Fc
      gamma R and CR3 was much greater than that of IC via Fc gamma R alone. Adding
      ethanol to the cells decreased iC3b-IC phagocytosis to that of IC, which was not
      affected by these reagents, suggesting that the enhanced phagocytosis is
      attributable to CR3-mediated phospholipase D activation. The IC phagocytosis was
      inhibited more effectively by anti-Fc gamma IIIB, whereas the iC3b-IC
      phagocytosis was partly inhibited only by anti-Fc gamma RII. The main Fc gamma R
      might differ in IC and iC3b-IC phagocytosis.

PMID- 7589464
TI  - Molecular cloning of a widely expressed human homologue for the Drosophila trp
      gene.
AB  - The Drosophila transient receptor potential (trp) gene and its homologue, trpl,
      have been suggested to mediate calcium entry during the insect's
      phototransduction process. We isolated a human cDNA, human trp-1 (Htrp-1),
      encoding a polypeptide of 793 amino acids that is 37% identical (62% similar) to
      Drosophila trp and trpl. Northern analysis showed that the Htrp-1 transcript is
      approximately 5.5 kb and expressed in most human tissues, with higher amounts in
      ovary, testis, heart, and brain. Isolation of Htrp-1 suggests that a trp-type
      protein is present in mammals and should provide a useful tool in studying
      calcium-depletion induced calcium influx processes.

PMID- 7589465
TI  - Identification of atypical (non-AT1, non-AT2) angiotensin binding sites with high
      affinity for angiotensin I on IEC-18 rat intestinal epithelial cells.
AB  - Specific high-affinity (Kd = 3.4 nM) binding sites for 125I-labelled angiotensin
      I ([125I]Ang I) were identified on an epithelial cell line (IEC-18) derived from
      the rat small intestine. The sites, which also have high affinity for Ang II, are
      insensitive to both AT1- and AT2-specific angiotensin receptor antagonists. The
      rank order of potency with which various angiotensin peptides inhibited [125I]Ang
      I binding to the cells (Ang I > or = Ang II > Ang(1-7) > [Sar1,Ile8]-Ang II >
      Ang(3-8) > Ang III) also distinguishes these sites from AT1 and AT2 angiotensin
      receptors.

PMID- 7589468
TI  - Alcohol dehydrogenase of class III: consistent patterns of structural and
      functional conservation in relation to class I and other proteins.
AB  - Class III alcohol dehydrogenase from the lizard Uromastix hardwickii has been
      characterized. This non-mammalian, gnathostomatous vertebrate class III form
      allows correlations of structures and functions of this class, the traditional
      class I alcohol dehydrogenase, and other well-studied proteins. Catalytically,
      results show similar recoveries and activities of all vertebrate class III forms
      independent of source, similar activities also in invertebrates but in lower
      amounts, and considerably higher specific activities in microorganisms.
      Structurally, variability patterns are consistent throughout the vertebrate
      system with a ratio in accepted point mutations versus class I of 0.4. This ratio
      between different classes of a zinc enzyme is comparable to that between
      different heme proteins (cytochrome c and myoglobin), suggesting defined but non
      identical functions also for the alcohol dehydrogenase classes.

PMID- 7589466
TI  - Cloning and sequencing of a cDNA encoding rat D-dopachrome tautomerase.
AB  - An enzyme which converts D-dopachrome into 5,6-dihydroxyindole has recently been
      isolated from rat liver. Enzymatic D-dopachrome conversion has been observed in
      extracts from all tissues examined of several species, including man. We have now
      cloned and sequenced a 628 bp long cDNA encoding the enzyme provisionally called
      D-dopachrome tautomerase. The cDNA was isolated by 3' and 5' rapid amplification
      and cloning of cDNA ends (RACE) from rat liver cells using degenerate
      oligonucleotide primers, deduced from the N-terminal peptide sequence of D
      dopachrome tautomerase. The cDNA contains an open reading frame encoding 118
      amino acids. Edman degradation of intact and of trypsin degraded D-dopachrome
      tautomerase fragments gave information on and corroborated 67% of the deduced
      protein sequence. A homology search in the EST database found a human cDNA
      encoding a peptide sharing 66% homology with the rat enzyme. The rat D-dopachrome
      tautomerase shares 27% homology with the rat macrophage migration inhibitory
      factor (MIF).

PMID- 7589467
TI  - Purification from human plasma of a tetrapeptide that potentiates insulin-like
      growth factor-I activity in chick embryo cartilage.
AB  - Human plasma has been shown to contain a low molecular weight factor that
      potentiates human IGF-I stimulation of glycosaminoglycan synthesis in chick
      embryo cartilage. The peptide was purified and characterized by Edman degradation
      and electrospray mass spectrometry. The primary structure determined was: Trp-Gly
      His-Glu. A homologous synthetic peptide similarly promoted matrix biosynthesis in
      cartilage exposed to IGF-I.

PMID- 7589469
TI  - Multiple gene products are produced from a novel protein kinase transcription
      region.
AB  - The nonmuscle/smooth muscle myosin light chain kinase (MLCK) and the kinase
      related protein (KRP) that lacks protein kinase activity are myosin II binding
      proteins encoded in the vertebrate genome by a true gene within a gene
      relationship. The genomic organization and expression result in the same amino
      acid sequence in different molecular contexts from two different sizes of mRNA.
      We report here the identification and characterization of a third size class of
      gene products. The protein appears to be a higher molecular weight form of MLCK
      with additional amino terminal tail sequence which might provide differential
      subcellular targeting characteristics.

PMID- 7589470
TI  - Two identical hydrophobic clusters are present on the same actin monomer:
      interaction between one myosin subfragment-1 and two actin monomers.
AB  - Two-dimensional hydrophobic clusters analysis (HCA) was used to compare the
      distribution of hydrophobic clusters along various actin sequence. HCA-deduced
      patterns were not altered by amino-acid variations throughout the evolution of
      actin and we observed similar hydrophobic motifs comprising myosin subfragment-1
      ATP-independent binding sites. HCA suggested the presence of two groups of
      identical hydrophobic motifs (A1 and A2) which bound on each side of the S1 (63
      kDa-31 kDa) connecting segment in relation with two actin monomers. This
      connection is important in communications between actin- and nucleotide-binding
      sites. We postulate that some relation and message between the two motifs A1 and
      A2 take place through myosin subfragment-1 (63 kDa-31 kDa) connecting segment.

PMID- 7589471
TI  - N-glycosylation-defective receptor for erythropoietin can transduce the ligand
      induced cell proliferation signal.
AB  - Erythropoietin receptor (EPOR) contains a single N-linked sugar in an
      extracellular domain. It has been suggested that an erythroleukemia cell line
      with high sensitivity to EPO expresses a high molecular mass form of EPOR, which
      appears to be a highly N-glycosylated form responsible for EPO-mediated signal
      transduction [Sawyer and Hankins (1993) Proc. Natl. Acad. Sci. USA 90, 6849
      6853]. To examine the role of the N-linked sugar chain, we prepared EPO-dependent
      cell lines expressing the wild-type EPOR and N-glycosylation-defective EPOR.
      There was little difference in the expression of EPOR on the cell surface, EPO
      binding kinetics, and EPO-induced cell proliferation between the clones
      expressing the mutant EPOR and those expressing the wild-type EPOR.

PMID- 7589472
TI  - Molecular cloning and functional characterization of a GABA/betaine transporter
      from human kidney.
AB  - The human homologue of the canine GABA/betaine transporter (BGT-1) was isolated
      from a kidney inner medulla cDNA library. The coding sequence predicts a 614
      amino acids protein with the typical features of neurotransmitter transporter
      family. The gene maps to chromosome 12p13 and, in addition to kidney, is also
      expressed in brain, liver, heart, skeletal muscle, and placenta. Functional
      studies reveal a Km = 20 microM for GABA transport and a coupling to Na+ and Cl-
      with a stoichiometry 3 Na+:2 Cl-:1 GABA. At 500 microM the GABA transport was
      inhibited by various compounds with the following potency order: quinidine >
      verapamil > phloretin > betaine.

PMID- 7589473
TI  - Chemical cross-linking leads to two high molecular mass aggregates of rat alpha 1
      beta 1 integrin differing in their conformation but not in their composition.
AB  - In order to detect protein interactions of the collagen/laminin receptor alpha 1
      beta 1 integrin, covalent chemical cross-linking was performed with the homo
      bifunctional, amine reactive reagents DSS (disuccinimidylsuberate) and DSP
      (dithiobis(succinimidylpropionate)). After cross-linking of the 190 kDa rat alpha
      1 integrin subunit, immunoblotting revealed two additional, immunoreactive, high
      molecular mass complexes (M(r) 240/290 k). Generation of the 240/290 kDa
      aggregates depended on the presence of the intact tertiary protein structure. As
      shown with immunoaffinity purified proteins, the 240/290 kDa aggregates consist
      exclusively of alpha 1 and beta 1 integrin subunits. No other cross-linked
      proteins associated with the alpha 1 or beta 1 subunit were detected. In contrast
      to the non-cross-linkable alpha 1 beta 1 integrin, the 240/290 kDa aggregates
      presumably represent active forms of the adhesion receptor, because both bound in
      vitro to collagen I and IV. This ability of alpha 1 beta 1 integrin to cross-link
      and produce two additional high molecular mass forms is shared by rat alpha 9
      beta 1 integrin. Thus, the cross-linking approach directly indicates that beta 1
      integrins occur in different conformations caused by variations in the folding
      and/or spatial arrangement of their subunits.

PMID- 7589474
TI  - Cardiolipin modulates the secondary structure of the presequence peptide of
      cytochrome oxidase subunit IV: a 2D 1H-NMR study.
AB  - The secondary structure of the presequence of cytochrome oxidase subunit IV (p25)
      was studied by circular dichroism and 2D nuclear magnetic resonance in micelles
      of dodecylphosphocholine (DPC) and mixed micelles of DPC and mitochondrial
      cardiolipin (CL). In both systems, alpha-helix formation was observed. The alpha
      helix stretches from the N- to the C-terminus with a break at the proline residue
      at position 13. Upon introduction of CL in the DPC micellar system, an increased
      stability of the helix was observed around proline13 and in the C-terminal half.
      This observation, together with reported results on specific interactions between
      CL and p25, led to the proposal of a two-state equilibrium of the alpha-helical
      conformation of p25, modulated by CL.

PMID- 7589477
TI  - DNA synthesis primed by mononucleotides (de novo synthesis) catalyzed by HIV-1
      reverse transcriptase: tRNA(Lys,3) activation.
AB  - HIV-1 RT is able to catalyze DNA synthesis starting from mononucleotides used
      both as minimal primers and as nucleotide substrates (de novo synthesis) in the
      presence of a complementary template. The rate of this process is rather slow
      when compared to the polymerization primed by an oligonucleotide. The addition of
      tRNA(Lys,3) to this system increased the de novo synthesis rate by 2-fold.
      Addition of low concentrations of agents able to modify protein conformation,
      such as urea, dimethylsulfoxide and Triton X-100, can activate the de novo
      synthesis by a factor 2 to 5. A dramatic synergy is observed in the presence of
      the three compounds since the stimulating effect of tRNA increases 10-15 times.
      These results suggest that compounds activating RT are able to induce a
      conformational change of the enzyme which results in a higher specific activity.
      Primer tRNA seems to play an important role in HIV-1 RT modification(s) leading
      to a polymerase having a higher affinity for the primer or the dTTP, but not for
      the template. The specificity of RT for the template is not influenced by changes
      in the kinetics or in the thermodynamic parameters of the polymerization
      reaction.

PMID- 7589476
TI  - [3H]9-Methyl-7-bromoeudistomin D, a caffeine-like powerful Ca2+ releaser, binds
      to caffeine-binding sites distinct from the ryanodine receptors in brain
      microsomes.
AB  - [3H]9-Methyl-7-bromoeudistomin D ([3H]MBED), the most powerful Ca2+ releaser from
      sarcoplasmic reticulum, specifically bound to the brain microsomes. Caffeine
      competitively inhibited [3H]MBED binding. [3H]MBED binding was markedly blocked
      by procaine, whereas that was enhanced by adenosine-5'-(beta,gamma
      methylene)triphosphate. The Bmax value was 170 times more than that of
      [3H]ryanodine binding. The profile of sucrose-density gradient centrifugation of
      solubilized microsomes indicated that [3H]MBED binding protein was different from
      [3H]ryanodine binding protein. These results suggest that there are MBED/caffeine
      binding sites in brain that are distinct from the ryanodine receptor and that
      MBED becomes an essential molecular probe for characterizing caffeine-binding
      protein in the central nervous system.

PMID- 7589475
TI  - Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the
      association of LIM and SH3 domains.
AB  - MLN 50 was previously identified in a cDNA library of breast cancer metastasis.
      In this study, we show that MLN 50, which is expressed at a basal level in normal
      tissues, is overexpressed in 8% of human breast carcinomas most often together
      with c-erbB-2. MLN 50 cDNA encodes a putative protein of 261 residues, named Lasp
      1 (LIM and SH3 protein) since it contains a LIM motif and a domain of Src
      homology region 3 (SH3) at the amino- and the C-terminal parts of the protein,
      respectively. Thus, Lasp-1 defines a new LIM protein subfamily.

PMID- 7589478
TI  - Principles of symmetrical organization for the pyruvate dehydrogenase complex.
AB  - The experimentally observed phenomenon of non-equimolarity for enzyme components,
      assembled into multienzyme complexes of the 2-oxo acid dehydrogenases family, is
      structurally interpreted to predict the only possible stable symmetrical
      distribution of peripheral components on the complex core. To obey the equivalent
      neighboring, that is necessary for unique self-assembled structures, we should
      deduce discrete conformational states for core subunits, those with different
      affinity for peripheral components. Two kinetically different types of substrate
      intermediate pathways through the lipoyl network of the mammalian pyruvate
      dehydrogenase complex follow from this structural theory. The theory predicts
      unusual kinetic behavior for the multienzyme complex.

PMID- 7589479
TI  - Electron cryomicroscopy of two-dimensional crystals of the H(+)-ATPase from
      chloroplasts.
AB  - The H(+)-ATPase from spinach chloroplasts was isolated and purified. Two
      dimensional crystals were obtained from the protein/lipid/detergent micelles by
      treatment with phospholipase and simultaneous removal of detergent and fatty
      acids by Biobeads. The resulting two-dimensionally ordered arrays were
      investigated by electron cryomicroscopy. The ordered arrays showed top view
      projections of CF0F1. The images were analysed by correlation averaging. In this
      view CF0F1 has dimensions of 11.4 x 9 nm. The average view shows a strongly
      asymmetric molecule, in contrast to the rather hexagonal features of CF1,
      previously analyzed from two-dimensional arrays. It is concluded that this is due
      either to an asymmetric structure and positioning of CF0 relative to CF1 or to a
      rearrangement of CF1 subunits induced by binding of CF0 to CF1.

PMID- 7589483
TI  - Thermal stability of the polyheme cytochrome c3 superfamily.
AB  - The cytochrome c3 superfamily includes Desulfovibrio polyheme cytochromes c. We
      report the characteristic thermal stability parameters of the Desulfovibrio
      desulfuricans Norway (D.d.N.) cytochromes c3 (M(r) 13,000 and M(r) 26,000) and
      the Desulfovibrio vulgaris Hildenborough (D.v.H.) cytochrome c3 (M(r) 13,000) and
      high molecular mass cytochrome c (Hmc), as obtained with the help of electronic
      spectroscopy, voltammetric techniques and differential scanning calorimetry. The
      polyheme cytochromes are denatured over a wide range of temperatures: the D.v.H.
      cytochrome c3 is highly thermostable (Td = 121 degrees C) contrary to the D.d.N.
      protein (Td = 73 degrees C). The thermostability of the polyheme cytochromes is
      redox state dependent. The results are discussed in the light of the structural
      and functional relationships within the cytochrome c3 superfamily.

PMID- 7589482
TI  - Detection of beta-1,2-mannosyltransferase in Candida albicans cells.
AB  - A particulate insoluble fraction from Candida albicans J-1012 (serotype A) strain
      cells was obtained as the residue after extracting a 105,000 x g pellet of cell
      homogenate with 1% Triton X-100. Incubation of this fraction with a
      mannopentaose, Man beta 1-->2Man alpha 1-->(2Man alpha 1-->)(2)2Man (alpha beta
      Man5), in the presence of GDP-mannose followed by high performance liquid
      chromatography showed the formation of a mannohexaose. Analysis of the product by
      1H NMR indicates that alpha beta Man5 was changed to Man beta 1-->2Man beta 1-
      >2Man alpha 1-->(2Man alpha 1-->)2 2Man (alpha beta Man6). This beta-1,2
      mannosyltransferase (ManTase) II activity was completely inhibited by Zn2+ and
      was not restored by the addition of EDTA. The corresponding enzyme fraction from
      C. albicans NIH B-792 (serotype B) strain cells, the mannan of which does not
      possess both the alpha beta Man5 and alpha beta Man6 side chains, also exhibited
      the same beta-1,2-ManTase II activity.

PMID- 7589481
TI  - Functional expression of the human CHIP28 water channel in a yeast secretory
      mutant.
AB  - The temperature-sensitive Saccharomyces cerevisiae mutant strain NY17, deficient
      in the secretory pathway (sec6-4 mutation), is used for the heterologous
      expression of the human CHIP28 water channel. After a heat-shock, the protein is
      present in partially purified post-golgi secretory vesicles. Immunodetection and
      water transport studies, directly made on the vesicles, showed that CHIP28 is
      highly expressed and active in the yeast membranes.

PMID- 7589480
TI  - Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain.
AB  - Interaction of the widely expressed Fas with its membrane-bound ligand (FasL)
      leads to rapid cell death via apoptosis. To avoid pathological tissue damage, the
      activity of FasL requires tight regulation. Here, we report that the Src homology
      3 (SH3) domain of Fyn binds to the proline-rich cytoplasmic region of FasL.
      Binding of the SH3 domain occurs between amino acid residues 44-71 which contains
      several potential SH3 interaction sites. This binding is specific, as SH3 domains
      of Lck, Grb2 and ras-GAP bind only weakly or not at all. We suggest that FasL
      activity may be modulated by SH3 domains of the src-like Fyn kinase.

PMID- 7589486
TI  - Expression and refolding of a high-affinity receptor binding domain from rat
      alpha 1-macroglobulin.
AB  - A recombinant version of the receptor binding domain of rat alpha 1-macroglobulin
      (RBDv) consisting of residues 1319-1474 has been expressed in E. coli.
      Competition experiments with 125I-labelled methylamine treated human alpha 2
      macroglobulin reveal that the alpha 1-macroglobulin-RBDv exhibit the same high
      affinity for the alpha 2-macroglobulin receptor as the entire 40 kDa light chain
      from rat alpha 1-macroglobulin. It is therefore concluded, that all determinants
      for receptor interaction reside in the C-terminal approx. 150 residues of the
      alpha-macroglobulin subunit.

PMID- 7589485
TI  - Apoptosis, DNA damage and ubiquitin expression in normal and mdx muscle fibers
      after exercise.
AB  - The current view indicates that after eccentric exercise myofibers are
      mechanically damaged and therefore an inflammatory and necrotic process occurs.
      In the present paper we examine the possibility that apoptosis plays a role in
      normal and dystrophin-deficient muscles after running. We analysed for apoptosis
      normal and dystrophin-deficient mouse muscles after a night of spontaneous wheel
      running followed by two days of rest. Terminal deoxynucleotidyl transferase
      mediated end-labeling of DNA in nuclei in tissue sections and gel electrophoresis
      of extracted DNA showed the presence of fragmented DNA. Furthermore, ubiquitin, a
      protein whose appearance is related to apoptosis, increased in muscles of both
      dystrophic and normal runner mice. The present findings which confirm that DNA
      damage is absent in muscles of sedentary mice but present in muscles of runner
      mice offer a new hypothesis on early events of muscle damage.

PMID- 7589484
TI  - Lack of elevated drug efflux in adriamycin-resistant immunoblastic B lymphoma
      cells with mdr1 overexpression.
AB  - A multidrug-resistant (MDR) subline of the immunoblastic B lymphoma cell line was
      established by sequentially selecting in increasing concentrations of adriamycin.
      The adriamycin-resistant cell line (HOB1/ADR) demonstrated resistance to a wide
      spectrum of chemotherapeutic agents including MDR drugs (Vinca alkaloids and
      anthracycline), antimicrotubule drug (colchicine), and DNA-damaging agents
      (cisplatin and mitomycin C). The expression of human mdr1 gene, as analyzed by RT
      PCR and Western blotting, revealed a 13-15-fold increase in resistant cells.
      Unexpectedly, HOB1/ADR cells demonstrated a lack of reduced accumulation and of
      enhanced efflux of adriamycin. More than 60% adriamycin was effluxed at the same
      rate in both cell lines within 10 min. In contrast, the initial rate of
      vincristine accumulation was reduced by 3 fold in this resistant cell line. The
      maximal level of vincristine accumulation was 50% lower in the resistant cells
      than the parental cells. The maximal efflux rate was enhanced by 5 fold in the
      resistant cells. Inhibition of vincristine resistance by verapamil associated
      with restoration of drug accumulation, suggesting that acquired resistance in
      these cells is due to P-glycoprotein. These studies demonstrated that
      immunoblastic B lymphoma cells selected for adriamycin resistance preferentially
      developed P-glycoprotein-mediated vincristine efflux which plays an important
      role in vincristine resistance. In contrast, the resistant cells did not elevate
      adriamycin efflux, suggesting an additional mechanism responsible for adriamycin
      resistance.

PMID- 7589487
TI  - Oxidative DNA damage by t-butyl hydroperoxide causes DNA single strand breaks
      which is not linked to cell lysis. A mechanistic study in freshly isolated rat
      hepatocytes.
AB  - In rat hepatocytes, DNA damage by t-butyl hydroperoxide (tBOOH) was measured by
      using the fluorimetric analysis of alkaline DNA unwinding. The electrophoretic
      profile of genomic DNA suggests single rather than double DNA strand breaks
      formation. Oxidative DNA modifications, measured as increased 8-hydroxy
      deoxyguanosine content, were not detected. Lysis of hepatocytes and DNA strand
      breaks induced by tBOOH did not correlate, indicating that both processes are not
      interconnected. Since o-phenanthroline prevents against tBOOH-mediated effects on
      both DNA and membrane integrity, we discussed about a putative role of iron.

PMID- 7589488
TI  - Delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: isolation of L
      cysteinyl-D-valine, a 'shunt' product, and implications for the order of peptide
      bond formation.
AB  - L-Cysteinyl-D-valine was isolated from incubations of L-glutamate, L-cysteine and
      L-valine with delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase and
      identified by 1H NMR and electrospray ionization MS. This is entirely consistent
      with our prior proposal (Shiau, C.-Y., Baldwin, J.E., Byford, M.F., Sobey, W.J.
      and Schofield, C.J. (1995) FEBS Lett. 358, 97-100) that the alpha-peptide bond
      between cysteine and valine is formed before the delta-peptide bond between alpha
      aminoadipate and cysteine. The inclusion of L-glutamate, an analogue of L-alpha
      aminoadipate, did not result in a detectable amount of tripeptide product, but
      did increase apparent yields of L-cysteinyl-D-valine. Conceivably, formation of
      the L-glutamyladenylate stimulates synthesis of the cysteinyl-valine dipeptide
      indirectly via a conformational change in the enzyme.

PMID- 7589489
TI  - Direct evidence for the presence of two external NAD(P)H dehydrogenases coupled
      to the electron transport chain in plant mitochondria.
AB  - Exogenous NADPH oxidation by purified mitochondria from both potato tuber and
      Arum maculatum spadix was completely and irreversibly inhibited by sub-micromolar
      diphenyleneiodonium (DPI), while exogenous NADH oxidation was inhibited to only a
      small degree. Addition of DPI caused the collapse of the membrane potential
      generated by NADPH oxidation, while the potential generated by NADH was
      unaffected. We conclude that there are two distinct enzymes on the outer surface
      of the inner membrane of plant mitochondria, one specific for NADH, the other
      relatively specific for NADPH, with both enzymes linked to the electron transport
      chain.

PMID- 7589491
TI  - Cathelicidins: a novel protein family with a common proregion and a variable C
      terminal antimicrobial domain.
AB  - A novel protein family, showing a conserved proregion and a variable C-terminal
      antimicrobial domain, and named cathelicidin, has been identified in mammalian
      myeloid cells. The conserved proregion shows sequence similarity to members of
      the cystatin superfamily of cysteine proteinase inhibitors. Cathelicidins are
      stored in the cytoplasmic granules of neutrophil leukocytes and release the
      antimicrobial peptides upon leukocyte activation. Some of these peptides can
      assume an alpha-helical conformation, others contain one or two disulfide bonds,
      still others are Pro- and Arg-rich, or Trp-rich. In addition to bacterial
      killing, some of these peptides exert additional functions related to host
      defense such as LPS-neutralization and promotion of wound healing.

PMID- 7589490
TI  - Crystallization and crystallographic investigations of the small subunit of mouse
      ribonucleotide reductase.
AB  - The R2 protein component of mouse ribonucleotide reductase has been obtained from
      overproducing Escherichia coli bacteria. It has been crystallized using NaCl as
      precipitant. The crystals are orthorhombic, space group C222(1), with cell
      dimensions a = 76.9 A, b = 108.9 A, c = 92.7 A and diffract to at least 2.5 A.
      The asymmetric unit of the crystals contains one monomer. Rotation and
      translation function searches using a model based on the weakly homologous E.
      coli R2 gave one significant peak. Rotation about a crystallographic 2-fold axis
      parallel to the a-axis produces an R2 dimer with dimer interactions very similar
      to those found for E. coli R2.

PMID- 7589492
TI  - Functional complementation of yeast phosphofructokinase mutants by the non
      allosteric enzyme from Dictyostelium discoideum.
AB  - Phosphofructokinase (PFK) from yeast has been replaced by the non-allosteric
      isozyme from the slime mold Dictyostelium discoideum. This has been achieved by
      overexpression of the latter in a PFK-deficient strain of Saccharomyces
      cerevisiae under the control of the PFK2 promoter. Transformants complemented the
      glucose-negative growth phenotype exhibiting generation times on glucose
      containing media similar to those of an untransformed strain being wild-type for
      yeast PFK genes. The PFK produced reacted with an antibody against D. discoideum
      PFK. It exhibited the same subunit size, quaternary structure and kinetic
      parameters than those of the wild-type enzyme, and was also devoid of specific
      regulatory properties.

PMID- 7589493
TI  - Modification of a specific tyrosine enables tracing of the end-to-end distance
      during apomyoglobin folding.
AB  - In order to follow the overall geometry of the apomyoglobin molecule during
      folding, we have converted a specific tyrosine residue into 3-nitro-tyrosine. The
      specificity of the modification was verified by proteolytic cleavage of the
      modified protein and mass spectroscopy of the resulting fragments. By measuring
      the energy transfer from the tryptophanyl side-chains to the modified residue the
      average end-to-end distance can be followed. The experiment shows that after
      initiation of folding the N- and C-termini are rapidly brought into proximity,
      possibly to a near-native distance.

PMID- 7589494
TI  - Crystallization of threonyl-tRNA synthetase from Thermus thermophilus and
      preliminary crystallographic data.
AB  - Threonyl-tRNA synthetase from Thermus thermophilus (ttTRS) has been overproduced
      in Escherichia coli, purified and crystallized in solutions containing ammonium
      sulfate and glycerol. The crystals grew in the orthorhombic space group C222(1)
      with unit cell dimensions a = 119.5 A, b = 120.0 A, c = 317.5 A. The asymmetric
      unit is constituted of two monomers and the crystals contain 66% solvent. This
      paper reports the first crystals of ttTRS and preliminary crystallographic
      results since the presumed crystals of ttTRS described in a previous paper [1]
      were crystals of aspartyl-tRNA synthetase [2].

PMID- 7589496
TI  - The complete Consensus V3 loop peptide of the envelope protein gp120 of HIV-1
      shows pronounced helical character in solution.
AB  - The disulfide bridge closed cyclic peptide corresponding to the whole Consensus
      V3 loop of the envelope protein gp120 of HIV-1 was examined by proton 2D-NMR
      spectroscopy in water and in a 20% trifluoroethanol/water solution. In water, NOE
      data support a beta-turn conformation for the central conservative GPGR region
      and point towards partial formation of a helix in the C-terminal part. Upon
      addition of trifluoroethanol, a C-terminal helix is formed. This is evidenced by
      NOE data, alpha-proton chemical shift changes and changes in the JN alpha vicinal
      coupling constants. The C-terminal helix is amphipathic and also occurs in other
      examined strains. It could therefore be an important feature for the functioning
      of the V3 loop.

PMID- 7589495
TI  - Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing
      hormone receptor genes are expressed in human skin.
AB  - Evidence is provided that human skin, the largest body organ exposed to multiple
      stressors, expresses proopiomelanocortin (POMC), corticotropin releasing hormone
      (CRH) and CRH-receptor (CRHR) genes in vivo. In vitro studies show that POMC and
      CRHR mRNAs are transcribed in melanocytes, cells derived from the neural crest,
      and in keratinocytes, cells derived from the ectoderm. CRH mRNA is transcribed in
      cultured melanocytes but not in keratinocytes. It is proposed that an equivalent
      of the 'hypothalamus-pituitary axis' composed of the CRH-CRHR-POMC loop is
      conserved in mammalian skin.

PMID- 7589497
TI  - Transition metal ions within human atherosclerotic lesions can catalyse the
      oxidation of low density lipoprotein by macrophages.
AB  - The oxidation of low density lipoprotein (LDL) in the arterial wall may
      contribute to atherogenesis. The oxidation of LDL by cells usually requires
      catalytically active transition metal ions. We show here some that gruel samples
      from human advanced atherosclerotic lesions are capable of catalysing the
      oxidation of LDL by macrophages as measured by thiobarbituric acid-reactive
      substances, enhanced electrophoretic mobility and increased macrophage uptake.
      This catalysis could be inhibited by pretreatment of the gruel with Chelex-100,
      which binds transition metal ions. The presence of catalytically active
      transition metal ions in atherosclerotic lesions may help to explain why LDL
      oxidation occurs at these sites.

PMID- 7589498
TI  - An immunodominant antigen of Brugia malayi is an asparaginyl-tRNA synthetase.
AB  - Lymphatic filariasis is caused by infection with the filarial nematodes Brugia
      malayi, Brugia timori, Wuchereria bancrofti and Onchocerca volvulus which
      collectively infect about 200 million persons throughout the world. Protein
      sequence homology analysis of a major nematode antigen suggested that it was a
      class II aminoacyl-tRNA synthetase. The overproduction, purification and
      verification that the major B. malayi antigen is an asparaginyl-tRNA synthetase
      is described.

PMID- 7589500
TI  - A new mutation in the pufL gene responsible for the terbutryn resistance
      phenotype in Rubrivivax gelatinosus.
AB  - Rubrivivax gelatinosus is a facultative phototrophic non-sulfur bacterium
      belonging to the beta subclass of the purple bacteria. A terbutryn-resistant
      mutant of R. gelatinosus has been isolated and characterized. Increased
      resistance levels to terbutryn (300-fold), atrazine (6-fold) and o-phenanthroline
      (3-fold) were observed for the mutant compared with wild type. Sequence analysis
      of the mutant revealed a new mutation in the pufL gene coding for the L subunit
      of the reaction centre (RC) at codon 192 leading to an amino-acid substitution
      from Gly in the wild type to Asp in the mutant. This substitution is located in
      the D helix of the L subunit, suggesting an interaction between terbutryn and
      this part of the polypeptide in the RC of R. gelatinosus. This is the first
      report of a mutation leading to herbicide resistance and affecting the D helix in
      purple bacteria. Furthermore R. gelatinosus wild type is highly sensitive to o
      phenanthroline compared with other purple bacteria (Rhodobacter capsulatus and
      Rhodobacter sphaeroides). Sequence comparison of the L subunit from six purple
      bacteria in which o-phenanthroline sensitivity was measured suggests that SerL226
      might be responsible for this phenotype.

PMID- 7589499
TI  - Specific neurotrophin binding to leucine-rich motif peptides of TrkA and TrkB.
AB  - The extracellular domains of the TrkA and TrkB neurotrophin receptors contain
      defined structural modules such as immunoglobulin-like domains and leucine-rich
      motifs (LRMs) [Schneider and Schweiger, Oncogene 6 (1991) 1807-1811]. Recently,
      the second LRM of TrkA was identified as a functional nerve growth factor (NGF)
      binding site [Windisch et al, J. Biol. chem. (1995) in press]. A peptide
      corresponding to this region effectively bound NGF and blocked binding of NGF to
      the recombinant extracellular domain of TrkA. The corresponding TrkB peptide
      exhibited the same effects with respect to brain-derived neurotrophic factor
      (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), indicating that all
      three TrkB ligands utilize this same binding site. Isolated LRMs therefore embody
      independent functional entities.

PMID- 7589501
TI  - Distribution of mRNA encoding the inwardly rectifying K+ channel, BIR1 in rat
      tissues.
AB  - The distribution of mRNA encoding the inwardly rectifying K+ channel, BIR1 [1]
      was investigated in rat tissues, and a comparison made with the expression of
      related genes rcKATP and GIRK1 using the reverse transcription-polymerase chain
      reaction (RT-PCR). This showed BIR1 to be expressed in all areas of the brain
      examined, in the eye but not in any other peripheral tissue. This pattern was
      distinct from rcKATP and GIRK1. Additional in situ hybridisation studies of the
      central expression of BIR1 demonstrated high levels of BIR1 mRNA in the
      hippocampus, dentate gyrus, taenia tecta and cerebellum and at lower levels in
      the cortex, habenular nucleus, olfactory bulb, primary olfactory cortex,
      thalamus, pontine nucleus and amygdaloid nucleus.

PMID- 7589502
TI  - Factor VIIa and the extracellular domains of human tissue factor form a compact
      complex: a study by X-ray and neutron solution scattering.
AB  - The four-domain structure of human factor VIIa and the two-domain structure of
      tissue factor form a tight complex to initiate blood coagulation. By solution
      scattering, the mean X-ray and neutron radii of gyration RG (which determine
      macro-molecular elongation) were found to be 3.25 nm, 2.13 nm and 3.14 nm (+/-
      0.13 nm) for factor VIIa, the extracellular region of tissue factor and their
      complex in that order. The mean cross-sectional radii of gyration RXS were 1.33
      nm, 0.56 nm and 1.42 nm (+/- 0.13 nm) in that order. The mean lengths were 10.3
      nm, 7.7 nm and 10.2 nm in that order. The data show that, in solution, the free
      proteins have extended domain structures, and the complex is formed by a compact
      side-by-side alignment of the two proteins along their long axes. The high
      binding affinity of tissue factor for factor VIIa may thus be accounted for by
      the occurrence of many intermolecular contacts in the complex.

PMID- 7589503
TI  - Regulation of intracellular pH by cell-cell adhesive interactions.
AB  - As was shown in our previous work, the intracellular pH (pHi) of cultured human
      fibroblasts depends on cell density. The pHi is low in single cells, higher in
      cells, forming small groups and maximal in a sparse monolayer. On the other hand,
      the pHi is low in areas of confluent monolayers. In the present work, we show
      that the effects of inhibitors of various pH-controlling mechanisms as well as
      inhibitors of key enzymes in signal transduction pathways depend on the local
      cell density. We have found that N-ethylmaleimide and 7-chloro-4-nitrobenz-2-oxa
      1,3-diazole, known as inhibitors of V-type H+ ATPase, inhibit the elevation of
      pHi induced by cell-cell contact interactions; meanwhile Cd2+ ions, which inhibit
      H+ conductive pathway, cause an increase of pHi in a confluent monolayer. Our
      data revealed also that the Na+/H+ antiporter does not play an essential role in
      the pHi regulation by intercellular contacts. Inhibitors of phospholipase A2 (4
      bromophenacyl-bromide), phospholipase C (neomycin) and protein kinase C (H-7)
      dramatically change the way the pHi is modulated by local cell density. It is
      suggested that cell-cell interactions regulate cell activities via modulation of
      pHi, which is under positive control from phospholipase A2 and under negative
      control from protein kinase C.

PMID- 7589504
TI  - A model for transmembrane helix with a cis-proline in the middle.
AB  - The presence of a higher percentage of Proline in the transmembrane helices of
      transport proteins indicates that they are involved in the function of these
      integral membrane proteins (IMPs). In many cases, the possible involvement of cis
      trans isomerization in function/folding of IMPs has been suggested. The
      introduction of cis-Pro in an ideal alpha-helix results in a helix-turn-helix
      motif. A molecular dynamics (MD) simulation is carried out on the sequence ACE
      (ALA)10-cis-Pro-(ALA)10-NME with ideal alpha-helical structure to investigate if
      and how a straight helix can accommodate a cis-Pro. The analysis of the
      conformations accessed during MD simulation showed that the residues near cis-Pro
      can adopt alternate conformations other than the right-handed helical
      conformation such that an almost straight helix is obtained. This may have
      implications in the involvement of cis-trans isomerization in folding and/or
      function of IMPs.

PMID- 7589505
TI  - Cloning, expression and characterization of human thioltransferase (glutaredoxin)
      in E. coli.
AB  - PCR primers were designed from the known amino acid (aa) sequence for human red
      blood cell thioltransferase (hRBC TTase) and the known cDNA sequence for pig
      liver TTase (82% homologous) and used to amplify thioltransferase from a pool of
      human brain cDNAs. The PCR product was inserted into the pKK233-2 expression
      vector. The DNA sequence of the insert agreed with the aa sequence. High level
      expression of the enzyme was accomplished in E. coli, and Western blot analysis
      confirmed its identity. Recombinant TTase displayed catalytic properties
      indistinguishable from natural hRBC TTase.

PMID- 7589506
TI  - Bimodal distribution of proteinase 3 (PR3) surface expression reflects a
      constitutive heterogeneity in the polymorphonuclear neutrophil pool.
AB  - Proteinase 3, which is known as an intracellular serine protease of neutrophils,
      was detected at the surface of a subpopulation of freshly isolated PMN. The
      proportion of PR3-positive and -negative PMN, observed by flow cytometry with
      anti-PR3 mAbs or ANCA autoantibodies, varies among individuals but is extremely
      stable for each individual over prolonged time periods. After PMN degranulation
      by FMLP with cyt. B, membrane PR3 expression increases but the proportion of low
      and high PR3-expressing cells remains stable. The existence of a subset of PMN
      which spontaneously expresses PR3 and varies among individuals, may be relevant
      to the pathogenesis of anti-PR3 ANCA autoantibody-related vasculitis.

PMID- 7589507
TI  - GCAP-II: isolation and characterization of the circulating form of human
      uroguanylin.
AB  - The systematic isolation of circulating regulatory peptides which generate cGMP
      as second messenger resulted in the identification of a novel member of the
      guanylin family. In the present study we describe the purification and amino acid
      sequence of a new guanylate cyclase C activating peptide (GCAP-II). GCAP-II
      contains 24 amino acids in the following sequence: FKTLRTIANDDCELCVNVACTGCL. Its
      molecular mass is 2597.7 Da. The 16 C-terminal amino acids are identical to
      uroguanylin from human urine. native and synthetic GCAP-II activate GC-C, the
      specific guanylate cyclase receptor, of cultured human colon carcinoma (T84)
      cells. GCAP-II stimulates chloride secretion in isolated human intestinal mucosa
      mediated by intracellular cGMP increase. GCAP-II specific antibodies were used to
      localize the peptide by immunohistochemistry in entero-endocrine cells of the
      colonic mucosa.

PMID- 7589508
TI  - Loss of allosteric behaviour in recombinant hemoglobin alpha 2 beta 2(92)(F8) His
      ->Ala: restoration upon addition of strong effectors.
AB  - In the stereochemical model proposed by Perutz [1], the Fe-His(F8) bond plays a
      significant role in the allosteric transition in hemoglobin and the resulting
      cooperativity in ligand binding. When this bond is ruptured, there is a loss in
      the transmission of the information concerning ligand binding; examples are
      Hb(NO)4 in the presence of inositol hexakisphosphate (IHP), or nickel substituted
      Hb hybrids which, despite being liganded, exhibit deoxy-like properties. To study
      the effects of the loss of the iron proximal histidine bond, we have engineered
      the alpha 2 beta 2(F8)H92A recombinant Hb. The replacement of the highly
      conserved proximal histidine F8 residue by an alanine results in a low affinity
      for the heme group and a loss of the allosteric properties; kinetics of CO
      recombination after photodissociation show only the rapid bimolecular phase,
      characteristic of the high affinity R-state. However, a significant amount of
      deoxy (T-state) kinetics are observed after addition of external effectors such
      as IHP. The iron-histidine bond is apparently crucial for the heme-heme
      interaction, but the allosteric equilibrium may still be influenced by external
      constraints.

PMID- 7589509
TI  - Marked depletion of GLUT4 glucose transporters in transverse tubules of skeletal
      muscle from streptozotocin-induced diabetic rats.
AB  - The principal goal of the present study was to determine the subcellular content
      of GLUT4 in diabetic rat muscle, and to test the hypothesis that a reduced
      abundance of the transporter protein in transverse tubules is responsible for
      impaired glucose utilization in that tissue. GLUT4 protein levels were measured
      in hindlimb muscle homogenates as well as in subcellular membrane fractions
      enriched with either plasma membranes, transverse tubules, or GLUT4-containing
      intracellular membranes from control and diabetic (streptozotocin-induced) rats.
      GLUT4 protein contents in diabetic muscle homogenates was reduced by 30% as
      compared to control rats. Subcellular fractionation experiments revealed that
      GLUT4 contents in transverse tubules-enriched fractions was markedly decreased
      (by 55-60%) in skeletal muscle of diabetic animals whereas no significant
      reductions in GLUT4 abundance was observed in the plasma membrane fraction.
      Moreover, GLUT4 was markedly depleted (by 45%) in the GLUT4-enriched
      intracellular membrane fraction. These results indicate that GLUT4 is markedly
      depleted in both the intracellular pool and in the cell surface membranes in
      muscle of STZ-diabetic rats. Most strikingly, this study demonstrates that
      transverse tubules and not the plasma membrane are the main sites of cell surface
      GLUT4 depletion in diabetic muscle.

PMID- 7589510
TI  - Thrombopoietin, c-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and
      STAT3, and enhances agonists-induced aggregation in platelets in vitro.
AB  - We investigated in vitro effects of recombinant human thrombopoietin (TPO), or c
      Mpl ligand, on human platelets. TPO induced rapid dose-dependent tyrosine
      phosphorylation of several proteins. We identified Janus tyrosine kinases, Tyk2
      and JAK2, and a member of STAT (signal transducers and activators of
      transcription) family, STAT3, as the tyrosine-phosphorylated proteins in response
      to TPO. TPO by itself did not cause platelet aggregation and shape change, but
      augmented ADP-induced aggregation in a dose-dependent manner. Acetylsalicylic
      acid inhibited the secondary aggregation enhanced by TPO, but not the TPO-induced
      potentiation of the primary aggregation. TPO modulates platelet activation
      possibly through protein-tyrosine phosphorylation.

PMID- 7589511
TI  - A novel gene family encoding proteins with highly differing structure because of
      a rapidly evolving exon.
AB  - Despite vast differences in primary structure, it is here shown that several
      predominant semen proteins are encoded by genes that belongs to a common family.
      Members have their transcription unit split into three exons: the first encoding
      the signal peptide, the second the secreted protein, while the third exon solely
      consists of 3' non-translated nucleotides. The first and the third exon are
      conserved between members, but the second exon is not. The genes for human
      semenogelins I and II, rat SVSII, SVSIV, SVSV and guinea pig GP1 and GP2 belong
      to this gene family.

PMID- 7589512
TI  - The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma.
AB  - The imprinted H19 gene is highly expressed in human embryos, fetal tissues and is
      nearly completely shut off in adults. However, it is reexpressed in a number of
      tumors including bladder carcinoma, demonstrating that H19 RNA is an oncofetal
      RNA. Tumors induced by injection of bladder carcinoma cell lines express H19 in
      contrast to the cells before injection. These observations support the notion of
      a positive correlation between H19 expression and bladder carcinoma. Loss of
      imprinting of H19 and IGF-2 was observed in samples of human bladder carcinoma.

PMID- 7589513
TI  - The role of the skeletal muscle myosin light chains N-terminal fragments.
AB  - The myosin regulatory and essential light chains in skeletal muscle do not play a
      role as significant as in scallop or smooth muscle, however, there are some data
      suggesting that the skeletal myosin light chains and their N-terminal parts may
      have a modulatory function in the interaction of actin with myosin heads. In this
      paper four conformational states of the myosin head with respect to the
      regulatory light chain bound cation (magnesium or calcium) and phosphorylation
      are proposed. Communication between regulatory and essential light chains and
      putative binding of the N-terminus of A1 essential light chain to actin is
      discussed.

PMID- 7589517
TI  - Stimulation of catecholamine secretion from adrenal chromaffin cells by 14-3-3
      proteins is due to reorganisation of the cortical actin network.
AB  - Catecholamine release from digitonin-permeabilized adrenal chromaffin cells is
      increased by exogenous 14-3-3 proteins. In order to determine how 14-3-3 proteins
      stimulate exocytosis their effect on the cortical actin network was examined.
      Increased amounts of beta and gamma isoforms of 14-3-3 proteins were associated
      with the Triton-insoluble cytoskeleton of chromaffin cells following incubation
      with exogenous 14-3-3 proteins. The stimulation of catecholamine release by 14-3
      3 proteins was abolished by prior incubation with the actin filament stabilising
      drug phalloidin. Rhodamine phalloidin staining showed that the cortical actin
      network was disassembled and actin reorganised into intracellular foci following
      treatment with 14-3-3 proteins. These data suggest that 14-3-3 proteins enhance
      catecholamine release in permeabilized chromaffin cells by reorganisation of the
      cortical actin barrier to allow increased availability of secretory vesicles for
      exocytosis.

PMID- 7589515
TI  - Down-modulation of c-kit mRNA and protein expression by erythroid differentiation
      factor/activin A.
AB  - We examined the effects of erythroid differentiation factor (EDF)/activin A on
      the expression of c-kit mRNA and protein in murine erythroleukemia (MEL) cells.
      EDF/activin A induced MEL cells to benzidine positive cells. Northern blot
      analysis showed that the c-kit mRNA expression was reduced synchronously with
      increase of beta-globin and uroporphyrinogen decarboxylase gene expression during
      EDF/activin A induced erythroid differentiation. Scatchard analysis indicated
      that the cell surface receptor number was reduced without change of affinity
      during differentiation. Our results suggest that EDF/activin A may act as a
      natural regulator of erythropoiesis with modulation of c-kit gene expression.

PMID- 7589518
TI  - NADPH-sulfite reductase flavoprotein from Escherichia coli: contribution to the
      flavin content and subunit interaction.
AB  - The flavoprotein component (SiR-FP) of the sulfite reductase of E. coli is an
      octamer of the 66 kDa alpha subunit. It was shown to be cleaved in two peptide
      fragments. The 23 kDa fragment has been purified as a polymer of 8-10 subunits.
      It corresponds to the N-terminal part of the native protein and was shown to
      contain essentially FMN as cofactor. The 43 kDa fragment is monomeric. It
      contains exclusively FAD and remains able to catalyze efficiently NADPH-dependent
      reductions. One can conclude that each alpha-chain of SiR-FP is composed of two
      distinct domains, one binding FAD and the other FMN and that the FMN-binding
      domains cooperate for a head-to-head subunit interaction.

PMID- 7589519
TI  - Changes in the histidine residues of Cu/Zn superoxide dismutase during aging.
AB  - Cu/Zn-Superoxide dismutase activity (Cu/Zn-SOD) was studied in liver from 3- and
      24-month-old rat. A significant decrease of enzyme activity in liver of the aged
      rat was found. Various amino acid residues and protein carbonyl groups (CO) were
      measured in purified young and old enzyme. It was found that the 'old' enzyme had
      one histidine fewer and higher CO content than the 'young' Cu/Zn-SOD.
      Inactivation 'in vitro' of purified commercial bovine erythrocyte Cu/Zn-SOD led
      to a decrease in the enzymatic activity, an increase in the CO and one histidine
      residue modified. A similar behavior between aging and oxidation was suggested.

PMID- 7589514
TI  - Specific RNA cleavages induced by manganese ions.
AB  - The specificity and efficiency of manganese ion-induced RNA hydrolysis was
      studied with several tRNA molecules. In case of yeast tRNA(Phe), the main
      cleavage occurs at p16 and minor cuts at p17-18, p20-21, p34 and p36-37. The
      major Mn(II)-induced cut in yeast elongator tRNA(Met) is also located in the D
      loop at p16 and it is stronger than that observed in tRNA(Phe). In initiator
      tRNA(Met) from yeast two strong Mn(II) cleavages of equal intensity occur at p16
      and p17. This is in contrast with single, much weaker cuts induced in the D-loop
      of that tRNA by Mg(II), Eu(III) and Pb(II) ions. Interestingly, in case of yeast
      tRNA(Glu) the main cleavage caused by Mn(II), Mg(II) and Pb(II) ions occurs in
      the anticodon loop. The involvement of hypermodified base mnm5s2U in this
      cleavage was ruled out based on results obtained with in vitro transcript of
      yeast tRNA(Glu) anticodon arm. Mutation of a single base A37G in the anticodon
      loop of the transcript drastically reduced the specificity of Mn(II)-induced
      hydrolysis.

PMID- 7589516
TI  - Reconstitution of the metal-tetracycline/H+ antiporter of Escherichia coli in
      proteoliposomes including F0F1-ATPase.
AB  - The tetracycline resistance gene (tetA) was cloned downstream of the lac
      promoter. When expression of the tetA gene in E. coli cells carrying the lac Iq
      gene was induced with isopropyl beta-D-thiogalactopyranoside, the tetracycline
      resistance protein (TetA) was overproduced, amounting to about 30% of the
      integral cytoplasmic membrane protein. Essentially pure TetA protein could be
      obtained by solubilization with 1.25% n-octyl-beta-D-glucopyranoside and one-step
      purification by DEAE Sepharose CL-6B column chromatography. The TetA protein was
      incorporated into proteoliposomes with F0F1-ATPase. The proteoliposomes exhibited
      [3H]tetracycline transport dependent on ATP hydrolysis. The specific activity was
      about 2 nmol/mg protein/min. The proteoliposomes also showed H+ efflux coupled
      with tetracycline influx. Tetracycline/H+ antiport by proteoliposomes
      reconstituted with the Ser-65-->Cys mutant TetA protein was inhibited by N
      ethylmaleimide. These results proved for the first time that the tetracycline/H+
      antiport is only mediated by the TetA protein.

PMID- 7589521
TI  - Reduction of the tyrosyl radical and the iron center in protein R2 of
      ribonucleotide reductase from mouse, herpes simplex virus and E. coli by p
      alkoxyphenols.
AB  - The rate of reduction of the tyrosyl radical in the small subunit of
      ribonucleotide reductase (protein R2) from E. coli, mouse, and herpes simplex
      virus (HSV-2) by a series of p-alkoxyphenols with different alkyl chains, have
      been studied by stopped-flow UV-vis and stopped-flow EPR spectroscopy. The
      reduction and release of iron in R2 by the inhibitors was followed using
      bathophenanthroline as chelator of Fe2+. p-Alkoxyphenols reduce the mouse R2
      tyrosyl radical 1-2 orders of magnitude faster than the HSV-2 and E. coli
      radical. In contrast to E. coli, the iron center in R2 from mouse and HSV-2 is
      reduced by the inhibitors. For mouse R2, the rate of reduction of the tyrosyl
      radical increases in parallel with increasing alkyl chain length of the
      inhibitor, an observation which may be important for the design of new
      antiproliferative drugs.

PMID- 7589520
TI  - Determination and cellular localization of adenylyl cyclase isozymes expressed in
      embryonic chick heart.
AB  - Mammalian heart has been reported to express AC isozymes (types V and VI) that
      are inhibited by < microM [Ca2+]; avian heart has been reported to express
      adenylyl cyclase activity that is inhibited by < microM [Ca2]. We have used
      reverse transcription polymerase chain reaction (RT-PCR) to determine that type V
      and VI AC mRNAs are present in freshly isolated ventricular myocytes. Subsequent
      RNase protection assays revealed that that the type V signal is 4-5 times that
      for the type VI isozyme. In situ hybridization with high specific activity cRNA
      probes combined with immunocytochemistry with a chick anti-myosin antibody was
      used to probe the cellular origins of type V and type VI AC signals. These
      studies show that myocytes contain messages for both the type V and VI isozymes
      but that AC V is the major isoform. Interestingly, while the type V AC mRNA
      appears to be localized primarily, if not exclusively, in myocytes, the signal
      for type AC VI mRNA in non-myocytes is stronger than in myocytes.

PMID- 7589522
TI  - Does Vav bind to F-actin through a CH domain?
AB  - An actin-binding protein domain we call here 'calponin-homology' or CH is present
      in signalling proteins such as Vav which are involved in activation and
      inactivation of small G-proteins. Using profile methods, we have detected two
      repeats of this domain in the actin-binding region of alpha-actinin and related
      proteins. Based on this, we propose that CH domain in Vav and other signalling
      proteins is employed for association with filamentous actin, and that this
      function correlates with their control on the G-proteins Rac and Rho which are
      involved in the organization of cytoskeleton.

PMID- 7589523
TI  - Transfer of rps10 from the mitochondrion to the nucleus in Arabidopsis thaliana:
      evidence for RNA-mediated transfer and exon shuffling at the integration site.
AB  - Rps10, a gene coding for ribosomal protein S10 of Arabidopsis mitochondria has
      been transferred to the nuclear compartment, while in pea and potato the active
      rps10 is mitochondrially located. The nuclear rps10 gene contains an intron at
      the junction of the target signal sequence and the mitochondrial-derived
      sequence, indicating that exon shuffling may have been involved in the addition
      of the transit peptide signal. Sequence comparison of Arabidopsis rps10 to the
      plant mitochondrial counterparts shows that the edited version is present in the
      nucleus of Arabidopsis. This finding corroborates RNA as an intermediate of a
      functional gene transfer between mitochondria and the nucleus. In vitro
      translated RPS10 protein is efficiently imported into potato mitochondria and a
      presequence of about 7 kDa is removed resulting in a mature protein that is
      larger compared to organellar and bacterial RPS10 proteins.

PMID- 7589525
TI  - Investigation of transphosphorylation between chemotaxis proteins and the
      phosphoenolpyruvate:sugar phosphotransferase system.
AB  - Transphosphorylation between the chemotaxis proteins and
      phosphoenolpyruvate:sugar phosphotransferase system (PTS) from Escherichia coli
      was investigated by incubating the CheA, CheW and CheY proteins of the chemotaxis
      cascade, and Enzyme I, HPr and Enzyme IImtl of the PTS with [gamma-32P]ATP or
      [32P]phosphoenolpyruvate in the presence and absence of cell extract. In the
      absence of cell extract, ATP phosphorylated CheA, but in the presence of cell
      extract, Enzyme I was also phosphorylated. Phosphoenolpyruvate phosphorylated
      only PTS components. The transphosphorylation of Enzyme I by ATP did not require
      chemotaxis proteins, and likely occurred through acetate kinase. Regardless of
      phosphorylation state, the HPr protein did not inhibit the rate of ATP-dependent
      phosphorylation of the CheA or the CheY protein. It is concluded that chemotaxis
      to PTS substrates is not mediated by transphosphorylation between the PTS and
      chemotaxis systems.

PMID- 7589524
TI  - Reconstitution photoactive yellow protein from apoprotein and p-coumaric acid
      derivatives.
AB  - We report reconstitution of photoactive yellow protein (PYP) from apoPYP and p
      coumaric acid derivatives. The addition of p-coumaric acid to the apoPYP sample
      did not result in the recovery of PYP. In contrast, yellow products were obtained
      by the addition of p-coumaryl thiophenyl ester or p-coumaric anhydride to the
      apoPYP sample, the absorption spectra of which were indistinguishable from the
      spectrum of intact PYP. Our findings provide strong evidence that PYP has the p
      coumaryl chromophore. This reconstitution technique opens the way for further
      biophysical studies of PYP using artificial chromophore analogs.

PMID- 7589526
TI  - Tubulin-tyrosine ligase catalyzes covalent binding of 3-fluoro-tyrosine to
      tubulin: kinetic and [19F]NMR studies.
AB  - The use of 3-fluoro-tyrosine as an alternative substrate for the enzyme
      tubulin:tyrosine ligase which catalyzes the incorporation of tyrosine into the
      alpha-tubulin subunit was investigated. The incorporation of tyrosine into
      tubulin was inhibited competitively by 3-fluoro-tyrosine with an apparent Ki of
      approximately 25 microM. The affinity for this analog was similar to that of
      tyrosine, confirming that the hydrogen at position 3 of the aromatic ring is not
      essential for the reaction catalyzed by TTLase. The incorporation of 3-fluoro
      tyrosine into the C-terminus of the alpha-tubulin subunit was demonstrated
      through [19F]NMR spectroscopy. The 3-fluoro-tyrosine signal at -58.6 ppm
      (trifluoroacetic acid as external standard), with a bandwidth of 24.7 Hz
      presented a chemical shift of 0.75 ppm upfield and an enlargement in the
      bandwidth (30.5 Hz) when incorporated into tubulin. These results strongly
      suggest that this amino acid is exposed to the solvent in tubulin. Tubulin
      covalently labeled with 3-fluoro-tyrosine was competent to polymerize into
      microtubules. The use of fluorinated tubulin in [19F]NMR spectroscopy for
      studying questions concerning protein conformation and interactions will be
      discussed.

PMID- 7589527
TI  - Calcium controls phage T5 infection at the level of the Escherichia coli
      cytoplasmic membrane.
AB  - Phage T5 requires 0.1 mM calcium to produce phage progeny in Escherichia coli
      cells. Decreasing calcium below 0.1 mM at time phage DNA was transferred depleted
      the bacteria of K+, caused membrane depolarization, perturbation of phage DNA
      transfer and resulted in a low internal ATP level. Our data suggest that calcium
      controls the conformation of the channel involved in the transfer of phage DNA
      through the host envelope and that below 0.1 mM calcium the channel remains open.
      This creates an energetic state of the host unfavorable to the synthesis of phage
      components and leads to abortion of the infectious process.

PMID- 7589528
TI  - Altered P450 activity associated with direct selection for fungal azole
      resistance.
AB  - Azole antifungals inhibit CYP51A1-mediated sterol 14 alpha-demethylation and the
      mechanism(s) of resistance to such compounds in Ustilago maydis were examined.
      The inhibition of growth was correlated with the accumulation of the substrate,
      24-methylene-24,25-dihydrolanosterol (eburicol), and depletion of ergosterol.
      Mutants overcoming the effect of azole antifungal treatment exhibited a unique
      phenotype with leaky CYP51A1 activity which was resistant to inhibition. The
      results demonstrate that alterations at the level of inhibitor binding to the
      target site can produce azole resistance. Similar changes may account for fungal
      azole resistance phenomena in agriculture, and also in medicine where resistance
      has become a problem in immunocompromised patients suffering from AIDS.

PMID- 7589529
TI  - Comparisons of P-glycoprotein expression in isolated rat brain microvessels and
      in primary cultures of endothelial cells derived from microvasculature of rat
      brain, epididymal fat pad and from aorta.
AB  - In vivo expression of P-glycoprotein in isolated rat brain microvessels is
      compared with that in vitro in primary cultures of brain endothelial cells. More
      P-glycoprotein is detected by Western immunoblotting in microvessels than in
      cultured endothelium. RT-PCR with isoform-specific primers and immunoblotting
      with a mdr1b-specific antibody reveals only mdr1a in vivo but both mdr1a and
      mdr1b in vitro. Thus mdr1a decreases whereas mdr1b increases during culture. P
      Glycoprotein activity is evident in vitro, with resistance modulators, e.g.
      verapamil, producing increases in intracellular [3H]vincristine accumulation.
      Endothelial cells cultured from epididymal fat pad microvasculature and aorta
      contain little or no P-glycoprotein. Here, resistance modulators are less
      effective.

PMID- 7589531
TI  - Insulin stimulates hormone-sensitive cyclic GMP-inhibited cyclic nucleotide
      phosphodiesterase in rat brown adipose cells.
AB  - The presence and regulation of a hormone-sensitive cyclic GMP-inhibited cyclic
      nucleotide phosphodiesterase (cGI PDE) in rat brown adipose cells was
      investigated. cDNA clones for two cGI PDE isoforms, cGIP1 and cGIP2, have been
      isolated. Using a rat cGIP1 (RcGIP1) cDNA probe, RcGIP1 mRNA (approximately 5.3
      kb) was detected in Northern blots of both brown and white adipose RNA. cGI PDE
      was detected in both microsomal and plasma membrane fractions of brown and white
      adipose cells by Western blotting using anti-RcGIP1 peptide antibody. When cells
      were incubated with insulin before membrane preparation, cGI PDE activity in the
      microsomal fraction was increased by 2- to 2.5-fold within 10 min. Isoproterenol
      also stimulated the activity of cGI PDE in the microsomal fraction by 1.5-fold.
      In cells incubated with both insulin and isoproterenol, microsomal cGI PDE
      activity was similar to that in microsomal fractions isolated from cells
      incubated with insulin alone. These results suggest that the hormonal regulation
      of cGI PDE, presumably a cGIP1 isoform, in rat brown adipose cells is similar to
      that in white adipose cells.

PMID- 7589530
TI  - Tissue-specific regulation of the expression of rat intestinal bile acid-binding
      protein.
AB  - A lipid-binding protein identical to the rat intestinal bile acid-binding
      protein, termed I-15P, was expressed in steroid hormone-producing tissues such as
      ovary and adrenal gland, but not testis. In immature rats, I-15P was expressed in
      intestine but not in ovaries. The expression of I-15P in the ovaries of immature
      rats was induced to the level in immature rats by gonadotropin treatment. This
      suggests that the expression of I-15P in the ovaries is controlled by the ovarian
      cycle. The present results indicate that the expression of I-15P is
      developmentally and hormonally controlled in a tissue-specific manner.

PMID- 7589532
TI  - Horseradish peroxidase inhibition by thiouracils.
AB  - In this paper, the activity of horseradish peroxidase was further determined in
      the presence of several uracil derivatives. The rate of guaiacol peroxidation
      decreases in presence of 2-thiouracil and of 6-n-propyl-2-thiouracil, but is not
      changed by 6-n-propyluracil nor uracil. Thus, thiouracils inhibit horseradish
      peroxidase in a noncompetitive form. The binding of 6-n-propyl-2-thiouracil, 2
      thiouracil, 6-n-propyluracil and uracil with horseradish peroxidase shows
      difference spectra due to changes in the environment of heme group in peroxidase.
      Then, the binding sites for these uracil derivatives are in an hydrophobic pocket
      at the heme periphery of peroxidase. The lesser binding rates were for uracil and
      propyluracil, which did not inhibit the peroxidase activity. These results point
      to the thiol group in uracils as responsible for the inhibition of peroxidase
      activity through interaction with an allosteric binding site, in peroxidase heme
      environment.

PMID- 7589533
TI  - Involvement of the three inter-alpha-trypsin inhibitor (ITI) heavy chains in each
      member of the serum ITI family.
AB  - Partial cDNAs coding for each of the three human inter-alpha-trypsin inhibitor
      (ITI) heavy chains were expressed in a bacterial plasmid system and rabbits were
      immunised with the fusion peptides obtained. Despite the strong sequence homology
      of these chains, the antisera turned out to be highly specific in the analysis of
      corresponding mRNA translation products or partially digested serum ITI. Besides
      classical serum ITI members, their use in Western blotting made it possible to
      evidence an H3-related ITI form and a low-amount H1-related HC/bikunin component.
      The relative levels of ITI family members was further studied in baboon and
      foetal calf sera.

PMID- 7589534
TI  - Isolation of an active and heat-stable monomeric form of Cu,Zn superoxide
      dismutase from the periplasmic space of Escherichia coli.
AB  - We have purified the Cu,Zn superoxide dismutase (CuZnSOD) from the periplasmic
      space of an Escherichia coli strain unable to synthesize MnSOD and FeSOD. Gel
      filtration chromatography evidenced that under all the experimental conditions
      tested the enzyme was monomeric. The catalytic activity of this CuZnSOD was
      comparable to that of other well characterized dimeric eukaryotic isoenzymes,
      indicating that a dimeric structure is not essential to ensure enzymatic
      efficiency. Furthermore the purified enzyme proved to be highly heat-stable and,
      uniquely among CuZnSODs, protease-sensitive. The latter property may explain the
      previously described lability of this protein in cell extracts.

PMID- 7589535
TI  - Evidence for specific, high-affinity binding sites for a proteinaceous elicitor
      in tobacco plasma membrane.
AB  - Binding of cryptogein, a proteinaceous elicitor, was studied on tobacco plasma
      membrane. The binding of the [125I]cryptogein was saturable, reversible and
      specific with an apparent Kd of 2 nM. A single class of cryptogein binding sites
      was found with a sharp optimum pH for binding at about pH 7.0. The high-affinity
      correlates with crytogein concentrations required for biological activity in
      vivo.

PMID- 7589536
TI  - Characterization of the cleavage specificity of a subtilisin-like serine
      proteinase from Ophiostoma piceae by liquid chromatography/mass spectrometry and
      tandem MS.
AB  - A proteinase secreted by the sapstaining fungus Ophiostoma piceae is thought to
      be necessary for the primary retrieval of nitrogen from wood proteins. By using
      mass spectrometry (MS) techniques, we have established the cleavage specificity
      of this subtilisin-like serine proteinase. This work demonstrated the potential
      of MS in determining cleavage specificities of newly isolated proteinases in a
      relatively short time frame, and determined that the O. piceae proteinase showed
      a substrate specificity similar to that of proteinase K. Primary cleavage of the
      insulin B-chain occurred between Leu15 and Tyr16. In addition numerous secondary
      cleavage sites occurred after hydrophobic, polar, and charged amino acids
      indicating a broad specificity.

PMID- 7589538
TI  - A region of the 75 kDa neurotrophin receptor homologous to the death domains of
      TNFR-I and Fas.
AB  - Members of the NTR/TNFR family mediate apoptosis in many tissues, yet sequence
      homology has not been detected in their intracellular domains except for a 'death
      domain' in TNFR-I and Fas. Here, a region of the 75 kDa neurotrophin receptor
      (NTR) has been aligned with this apoptosis-inducing motif. Peptides at the
      carboxyl terminus of each domain potentially form amphiphilic helices, one of
      which (in NTR) resembles mastoparan, a G-protein activating peptide. Molecular
      models of three death-region peptides suggest that observed sequence similarities
      reflect a common structure, perhaps capable of undergoing an induced coil to
      helix transition.

PMID- 7589539
TI  - Crystal structure of Bacillus licheniformis 1,3-1,4-beta-D-glucan 4
      glucanohydrolase at 1.8 A resolution.
AB  - The crystal structure of the 1,3-1,4-beta-D-glucan 4-glucanohydrolase from
      Bacillus licheniformis is solved at a resolution of 1.8 A and refined to R =
      16.5%. The protein has a similar beta-sandwich structure as the homologous enzyme
      from Bacillus macerans and the hybrid H(A16-M). This demonstrates that the
      jellyroll fold of these proteins is remarkably rigid and only weakly influenced
      by crystal contacts. The crystal structure permits to extend mechanistic
      considerations derived for the B. licheniformis enzyme to the entire class of
      bacterial 1,3-1,4-beta-D-glucan 4-glucanohydrolases.

PMID- 7589537
TI  - Trigger factor, one of the Escherichia coli chaperone proteins, is an original
      member of the FKBP family.
AB  - The trigger factor of Escherichia coli is known as a chaperone protein which
      forms soluble complexes with the precursor to outer membrane protein A and
      assists in the maintenance of translocation competence. Sequence analysis shows
      that trigger factor contains a domain belonging to the FK506-binding protein
      (FKBP) family and possessing all the amino acids necessary for FK506 binding and
      peptidyl-prolyl cis-trans isomerase (Ppiase) activity. Consequently, this protein
      could be directly involved in the unfolding/folding processes occurring during
      translocation across the E. coli plasma membrane and, more generally, in
      facilitating protein folding. The central position of the FKBP domain within the
      trigger factor sequence as well as several original features of the loops
      surrounding the FK506-binding pocket are not found in any other FKBPs, making it
      undetectable by the Fkbp-Ppiase signature patterns.

PMID- 7589540
TI  - Rapid purification of malate synthase from cotyledons of Brassica napus L.
AB  - A rapid and efficient method for the purification of malate synthase, an enzyme
      uniquely confined to glyoxysomes, from cotyledons of Brassica napus L. has been
      developed. The two step purification procedure is based on the consequent
      utilization of the tendency of malate synthase to form high molecular weight
      aggregates. Malate synthase was purified 75-fold to apparent homogeneity with a
      specific activity of 180 nkat/mg protein. The estimated molecular weight of
      malate synthase subunits was 63 kDa. Polyclonal antibodies raised against malate
      synthase in rabbits detect on Western blots only one single polypeptide with an
      identical molecular weight.

PMID- 7589541
TI  - Nitrogen oxide-induced autoprotection in isolated rat hepatocytes.
AB  - Pretreatment of rat hepatocytes with low-dose nitrogen oxide (addition of SNAP in
      vitro or induction of nitric oxide synthase in vitro or in vivo) imparts
      resistance to killing and decrease in aconitase and mitochondrial electron
      transfer from a second exposure to a higher dose of SNAP. Induction of this
      resistance is prevented by cycloheximide, indicating upregulation of protective
      protein(s). Ferritin levels are increased as are non-heme iron-NO EPR signals.
      Tin-protoporphyrin (SnPP) prevents protection, suggesting involvement of hsp32
      (heme oxygenase) and/or guanylyl cyclase (GC). Cross-resistance to H2O2 killing
      is also observed, which is also prevented by cycloheximide and SnPP. Thus,
      hepatocytes possess inducible protective mechanisms against nitrogen oxide and
      reactive oxygen toxicity.

PMID- 7589542
TI  - DNA strand breakage and base modification induced by hydrogen peroxide treatment
      of human respiratory tract epithelial cells.
AB  - Treatment of human respiratory tract epithelial cells with H2O2 led to
      concentration-dependent DNA strand breakage that was highly-correlated with
      multiple chemical modifications of all four DNA bases, suggesting that damage is
      due to hydroxyl radical, OH. However, the major base damage occurred to adenine.
      Hence, conclusions made about the occurrence and the extent of oxidative DNA
      damage on the basis only of changes in 8-hydroxyguanine should be approached with
      caution.

PMID- 7589543
TI  - Factors responsible for the Ca(2+)-dependent inactivation of calcineurin in
      brain.
AB  - The Ca(2+)-dependent protein phosphatase activity of crude rat brain extracts
      measured in the presence of okadaic acid, exhibits the characteristic properties
      of the calmodulin-stimulated protein phosphatase, calcineurin. It is stimulated
      more than 200-fold by Ca2+ and inhibited by the calmodulin-binding peptide, M13,
      and by the immunosuppressive drug, FK506. It is insensitive to rapamycin at
      concentrations up to 1 microM. Its specific activity, based on calcineurin
      concentration determined by quantitative analysis of Western blots exposed to
      anti-bovine brain IgG, is ten to twenty times that of purified rat brain
      calcineurin assayed under similar conditions. Unlike the purified enzyme it is
      rapidly and irreversibly inactivated in a time-, temperature-, and
      Ca2+/calmodulin-dependent fashion without evidence of extensive proteolytic
      degradation. The enzyme is converted to a state which does not lose activity by
      removal of low molecular weight material by gel filtration. Reconstitution of a
      labile enzyme is achieved by the addition of the low molecular weight-containing
      fraction eluted from the gel filtration column. These observations indicate that
      calcineurin in crude brain extracts is under the control of Ca2+/calmodulin
      dependent positive and negative regulatory mechanisms which involve unidentified
      endogenous factor(s).

PMID- 7589544
TI  - Ribozyme mediated cleavage of acute phase serum amyloid A (A-SAA) mRNA in vitro.
AB  - The 1000-fold induction of acute phase serum amyloid A (A-SAA) in the liver
      during inflammation indicates that this protein plays an important, though ill
      defined, role in host defence. Paradoxically, prolonged overproduction of A-SAA
      is a causative factor in secondary amyloidosis and possibly other diseases such
      as atherosclerosis; the ability to down-regulate A-SAA synthesis is therefore of
      considerable clinical importance. We have successfully generated anti-SAA
      hammerhead ribozymes and we report that they are capable of cleaving A-SAA mRNA
      in vitro.

PMID- 7589545
TI  - Divergent sequence motifs correlated with the substrate specificity of
      (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular
      polyketide synthases.
AB  - The amino acid sequences of a large number of polyketide synthase domains that
      catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl
      carrier protein (ACP) have been compared. Regions were identified in which the
      acyltransferase sequences diverged according to whether they were specific for
      malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to
      allow unambiguous assignment of newly-sequenced acyltransferase domains in
      modular polyketide synthases. Comparison with the recently-determined structure
      of the malonyltransferase from Escherichia coli fatty acid synthase showed that
      the divergent region thus identified lies near the acyltransferase active site,
      though not close enough to make direct contact with bound substrate.

PMID- 7589547
TI  - Point mutation of a conserved arginine (104) to lysine introduces
      hypersensitivity to inhibition by glyphosate in the 5-enolpyruvylshikimate-3
      phosphate synthase of Bacillus subtilis.
AB  - The role of a conserved arginine (R104) in the putative phosphoenol pyruvate
      binding region of 5-enolpyruvyl shikimate-3-phosphate synthase of Bacillus
      subtilis has been investigated. Employing site directed mutagenesis arginine was
      substituted by lysine or glutamine. Native and mutant proteins were expressed and
      purified to near homogeneity. Estimation of Michaelis and inhibitor constants of
      the native and mutant proteins exhibited altered substrate-inhibitor binding mode
      and constants. Mutation R104K hypersensitized the enzyme reaction to inhibition
      by glyphosate. The role of R104 in discriminating between glyphosate and
      phosphoenol pyruvate is discussed.

PMID- 7589548
TI  - The GA module, a mobile albumin-binding bacterial domain, adopts a three-helix
      bundle structure.
AB  - We present the first study of the secondary structure and global fold of an
      albumin-binding domain. Our data show that the GA module from protein PAB, an
      albumin-binding protein from the anaerobic bacterial species Peptostreptococcus
      magnus, is composed of a left-handed three-helix bundle. The helical regions were
      identified by sequential and medium range NOEs, values of NH-C alpha H coupling
      constants, chemical shift indices, and the presence of slowly exchanging amide
      protons, as determined by NMR spectroscopy. In addition, circular dichroism
      studies show that the module is remarkably stable with respect to both pH and
      temperature.

PMID- 7589546
TI  - In vivo inactivation of phosphotyrosine protein phosphatases by nitric oxide.
AB  - The effect of NO on phosphotyrosine protein phosphatases (PTPases) has been
      investigated in vivo. NO production is induced in interferon-gamma and
      lipopolysaccharide stimulated RAW-264.7 macrophages as indicated by the increase
      of NO2- in the medium. Our results demonstrate an inhibition of p
      nitrophenylphosphatase activity as a consequence of macrophages activation. Under
      the described experimental conditions, most of the hydrolysis of p
      nitrophenylphosphate can be ascribed to the action of cellular PTPases. The
      presence of NG-mono-methyl-L-arginine, a specific inhibitor of NO synthase
      decreases the inactivation rate of both membrane-bound and soluble PTPases. This
      evidence further confirms the ability of NO to inactivate PTPases and suggests a
      possible role of NO in the regulation of cellular processes involving this class
      of phosphatases.

PMID- 7589550
TI  - Stabilization of a semiquinone radical at the high-affinity quinone-binding site
      (QH) of the Escherichia coli bo-type ubiquinol oxidase.
AB  - Reaction of ubiquinone in the high-affinity quinone-binding site (QH) in bo-type
      ubiquinol oxidase from Escherichia coli was revealed by EPR and optical studies.
      In the QH site, ubiquinol was shown to be oxidized to ubisemiquinone and to
      ubiquinone, while no semiquinone signal was detected in the oxidase isolated from
      mutant cells that cannot synthesize ubiquinone. The QH site highly stabilized
      ubisemiquinone radical with a stability constant of 1-4 at pH 8.5 and the
      stability became lower at the lower pH. Midpoint potential of QH2/Q couple was -2
      mV at pH 8.5 and showed -60 mV/pH dependence indicative of 2H+/2e- reaction. The
      Em was more negative than that of low-spin heme b above pH 7.0. We conclude that
      the QH mediates intramolecular electron transfer from ubiquinol in the low
      affinity quinol oxidation site (QL) to low-spin heme b. Unique roles of the
      quinone-binding sites in the bacterial ubiquinol oxidase are discussed.

PMID- 7589549
TI  - Construction of a divalent cell adhesive lysozyme by introducing the Arg-Gly-Asp
      sequence at two sites.
AB  - To increase the cell adhesion activity of 74RGD4, an RGDS-inserted mutant between
      Val74 and Asn75 of human lysozyme, one more site for the RGD introduction was
      investigated in the lysozyme molecule. We found that 47RGD4 with RGDS in place of
      AGDR (residues 47 to 50) in a beta-turn region possesses the same level of
      adhesion activity as that of 74RGD4. The acceptance of the RGD introduction in
      the beta-turn region of human lysozyme is in good agreement with recent studies
      on the functional conformation of RGD. We constructed (47,74)RGD4, a mutant
      containing RGD at two sites, by combining the N-terminal domain of 47RGD4 and the
      C-terminal domain of 74RGD4. The (47,74)RGD4 lysozyme, with two functional RGD
      sequences, exhibits even higher cell adhesion activity than that of 74RGD4 or
      47RGD4.

PMID- 7589551
TI  - Expression of cytochrome P450 CYP1B1 in breast cancer.
AB  - The expression of CYP1B1 has been identified in breast cancer using the reverse
      transcriptase-polymerase chain reaction and immunoblotting. CYP1B1 mRNA was
      expressed in the majority of breast tumours and immunoblotting of breast tumours
      identified a single protein band of molecular weight 60 kDa corresponding to the
      predicted molecular weight of human CYP1B1. This is the first study to identify
      CYP1B1 expression in a tumour where it may represent a previously unknown pathway
      for the metabolism of oestradiol and chemotherapeutic drugs.

PMID- 7589552
TI  - Molecular and functional characterization of a partial cDNA encoding a novel
      chicken brain melatonin receptor.
AB  - An approach based on homology probing was used to clone a partial cDNA encoding a
      novel melatonin (ML) receptor (MLR) from chicken (Gallus domesticus) brain. Based
      on available deduced amino-acid sequence, the chicken MLR (cMLR) displayed
      greater sequence homology to the frog (Xenopus) MLR than cloned human/mammalian
      receptors, with overall identities of 73% and 66%, respectively. In order to gain
      functional expression, a chimeric frog/chicken (flc)MLR was constructed in which
      the 5' end of the cMLR, including the N-terminus, TM1 and part of the first
      intracellular loop was substituted by fMLR sequence. [125I]Iodo-ML bound with
      high affinity (Kd of approximately 35 pM) to COS-7 cells transiently expressing
      the flcMLR in a saturable and guanine nucleotide-sensitive manner with the
      following rank order of potency: 2-iodo-ML > ML > 6-Cl-ML > S20750 > 6-OH-ML >
      S20642 > S20753 > N-acetyl-5HT >> 5-HT. Estimated Ki values for these compounds
      at the flcMLR correlated well to those obtained in native chicken brain
      membranes. In line with the observed structural similarity to the fMLR, the
      flcMLR exhibited affinities for ML, 6-Cl-ML and 6-OH-ML approximately 10-fold
      lower than mammalian receptors. Functionally, opposing interactions between ML
      and dopamine receptor signal transduction pathways were observed with ML potently
      inhibiting dopamine D1A-receptor-mediated cAMP accumulation in cells (HEK-293)
      transiently co-expressing these receptors. cMLR mRNAs were found expressed in
      chicken brain and kidney with trace levels observed in the lung. The availability
      of cloned vertebrate MLRs distinct at both the amino acid and pharmacological
      level from their mammalian counterparts may now allow for the identification of
      those amino-acid residues and structural motifs that regulate ML-binding
      specificity and affinity.

PMID- 7589554
TI  - Coactosin interferes with the capping of actin filaments.
AB  - Coactosin, a 16 kDa protein associated with the actin cytoskeleton from
      Dictyostelium discoideum, was purified by an improved method, in which other
      components of the cytoskeleton were removed. The highly purified coactosin had no
      effect on the time course of actin polymerization, but when added to actin in
      presence of capping proteins, coactosin counteracted the capping activity of
      these proteins. The capping proteins cap32/34 and severin domain 1 retarded actin
      polymerization, on addition of coactosin to samples containing one of these
      capping proteins the time course of actin polymerization became close to controls
      without capping proteins.

PMID- 7589553
TI  - Helix-loop-helix transcription factors regulate Id2 gene promoter activity.
AB  - Id-like helix-loop-helix (HLH) transcription factors are involved in the
      regulation of proliferation and differentiation of several cell types. We
      isolated 5' regulatory region of mouse Id2 gene and demonstrated that it contains
      several E-box clusters. These E-boxes mediate stimulatory effects of basic-HLH
      (bHLH) transcription factors ME1, ME2, and NSCL1 on Id2 promoter activity. Co
      expression of Id2 blocks the stimulatory effect of bHLH transcription factors
      which suggests the presence of feedback loops in Id2 transcriptional regulation.
      Overexpression of NSCL1 in F9 cells blocks the downregulation of Id2 gene
      expression during retinoic acid induced differentiation. Our data demonstrate
      that bHLH transcription factors regulate Id2 gene expression.

PMID- 7589558
TI  - Conversion of short-chain ceramides to short-chain ceramide GM3 in B16 melanoma
      cells.
AB  - We report that short-chain ceramide (Cer), C2- and C6-Cer, were immediately
      glycosylated and finally converted to short-chain Cer GM3 in B16 melanoma cells.
      By addition of either C2- or C6-Cer to a cell culture of B16 melanoma in the
      presence of [14C]Gal, the radiolabeled precursor, was incorporated into each of
      two novel glycosphingolipids (GSLs) within 30 min along with synthesis of normal
      GSLs. These novel GSLs were identified as C2-, C6-Cer cerebrosides and C2-, C6
      Cer GM3, respectively. In comparison with C2-Cer, C6-Cer was found to be much
      more efficiently converted to the GSLs, whereas no glycosylated sphingosine was
      detectable when it was added in place of short-chain Cer.

PMID- 7589555
TI  - Deficient DNA repair of triple helix-directed double psoralen damage in human
      cells.
AB  - Damage induced by a single psoralen-modified triple helix-forming oligonucleotide
      has been reported to be efficiently repaired in human cells. In this study we
      investigated a set of psoralen coupled oligonucleotides introducing multiple
      lesions into the target DNA. A simian virus 40 (SV40) shuttle vector was in vitro
      treated with different triple helix-forming oligonucleotides and UVA radiation,
      leading to double psoralen adducts at the supF mutational target gene of the
      plasmid. After passage in the Raji human cell line the recovered vector was
      analysed in an indicator bacterial strain. The results show that double psoralen
      adducts, located at both ends of a long triple helix, cannot be repaired
      efficiently in human cells.

PMID- 7589556
TI  - Crystallization and preliminary diffraction studies of the structural domain E of
      Thermus flavus 5S rRNA.
AB  - The ribosomal 5S RNA is an essential constituent of the large ribosomal subunit.
      To overcome the difficulties of crystallizing large RNA molecules such as 5S
      rRNAs, we decided to divide the 5S rRNA in five domains A through E to determine
      their structure. Recently we determined the crystal structural of the helical
      domain A. Here we report the crystallization of the chemically synthesized domain
      E of the Thermus flavus 5S rRNA. The crystal form is trigonal with unit cell
      dimensions: a = b = 42.80 A and c = 162.20 A. Diffraction-data to 2.8 A have been
      recorded and the structure solution is currently underway by means of MIR and MAD
      techniques.

PMID- 7589557
TI  - Up-regulation of endothelial nitric oxide synthase expression by cyclic guanosine
      3',5'-monophosphate.
AB  - In this study, the role of cyclic GMP, the end product of the NO-cyclic GMP
      signalling pathway, in the regulation of ecNOS was investigated. Bovine pulmonary
      endothelial cells were exposed to 8-bromo-cyclic GMP and its effect on NO
      production, ecNOS protein, and mRNA levels was analyzed. Endothelial cells on
      exposure to 8-bromo-cyclic GMP produced significantly increased amounts of NO,
      detected as increased cyclic GMP in cocultures with vascular smooth muscle cells
      both under basal conditions and with agonist stimulation. 8-Bromo-cyclic GMP
      significantly increased the ecNOS protein and mRNA levels as detected on Western
      and Northern blots respectively. This 8-bromo-cyclic GMP mediated increase of NO
      production, ecNOS protein and mRNA levels suggests that cyclic GMP up-regulates
      the expression of ecNOS. Thus, there may be an intercellular feedback mechanism
      involved at the molecular level in the expression of the NO-cyclic GMP signalling
      pathway in blood vessels.

PMID- 7589559
TI  - An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli
      in human monocytic THP.1 cells.
AB  - Apoptosis was induced in THP.1 cells, a human monocytic tumour cell line, by
      diverse stimuli including cycloheximide, thapsigargin, etoposide and
      staurosporine. Induction of apoptosis by all these stimuli, except etoposide, was
      enhanced in the presence of the trypsin-like protease inhibitor, N alpha-tosyl-L
      lysinyl chloromethyl ketone (TLCK). Induction of apoptosis, assessed by
      morphological, flow cytometric and biochemical criteria, including proteolysis of
      poly(ADP-ribose) polymerase and cleavage of DNA to large kilobasepair fragments,
      was completely abrogated when cells were pretreated with an ICE-like protease
      inhibitor, Z-Val-Ala-Asp.fluoromethylketone. This suggested that an ICE homologue
      was a common mediator of apoptosis in THP.1 cells.

PMID- 7589561
TI  - Mutations in the putative pore-forming domain of CFTR do not change anion
      selectivity of the cAMP activated Cl- conductance.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) apparently forms Cl-
      channels in apical membranes of secretory epithelial cells. A detailed model
      describes molecular structure and biophysical properties of CFTR and the impact
      of various mutations as they occur in cystic fibrosis. In the present report
      mutations were introduced into the putative 6th alpha-helical transmembrane pore
      forming domain of CFTR. The mutants were subsequently expressed in Xenopus
      oocytes by injection of the respective cRNAs. Whole cell (wc) conductances could
      be reversibly activated by IBMX (1 nmol/l) only in oocytes injected with wild
      type (wt) or mutant CFTR but not in oocytes injected with water or antisense
      CFTR. The activated conductance was partially inhibited by (each 100 mumol/l)
      DIDS (27%) and glibenclamide (77%), but not by 10 mumol/l NPPB. The following
      mutations were examined: K335E, R347E, R334E, K335H, R347H, R334H. They did not
      measurably change the wt-CFTR anion permeability (P) and we conductance (G)
      sequence of: PCl- > PBr- > P1- and GCl- > GBr- > G1-, respectively. Moreover,
      anomalous mole fraction behavior for the cAMP activated current could not be
      detected: neither in wt-CFTR nor in R347E-CFTR. Various mutants for which
      positively charged amino acids were replaced by histidines (K335H, R347H, R334H)
      did not show pH sensitivity of the IBMX activated wc conductance. We, therefore,
      cannot confirm previous results. CFTR might have a different molecular structure
      than previously suggested or it might act as a regulator of ion conductances.

PMID- 7589563
TI  - The platelet endothelial cell adhesion molecule-1 (PECAM1) contributes to
      endothelial barrier function.
AB  - In this study we have analyzed the role of the platelet-endothelial cell adhesion
      molecule-1 (PECAM1) in vascular barrier function. PECAM1 is an immunoglobulin
      gene superfamily member expressed by endothelial cells at the cell boundaries.
      Macromolecule permeability assays performed on cell monolayers that express
      native or transfected PECAM1, indicated that the molecule participates in the
      establishment and maintenance of vascular barrier function in vitro. This
      hypothesis was confirmed by the finding that in vivo injection of the specific
      monoclonal antibody directed against the murine vascular PECAM1 led to a
      detectable leakage of hepatic and renal blood vessels.

PMID- 7589562
TI  - Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2
      tyrosine kinase.
AB  - The Jak kinases and Stat transcription factors play a major role in signaling of
      various cytokines including IFN alpha. In this report we show a ligand
      independent interaction between Tyk-2 and Jak-1 kinases. We also demonstrate that
      the Tyk-2 kinase forms a homodimer that has the ability to undergo intermolecular
      tyrosine phosphorylation. The formation of the Tyk-2 homodimer is independent of
      both tyrosine phosphorylation and the presence of the tyrosine kinase domain.

PMID- 7589564
TI  - Mutational analysis of the 3'-terminal extra-cistronic region of poliovirus RNA:
      secondary structure is not the only requirement for minus strand RNA replication.
AB  - A series of mutations were introduced in the 3'-terminal untranslated region (3'
      UTR) of full-length infectious poliovirus cDNA clones, and following transfection
      of COS-1 cells the ability of these constructs to generate viable viral particles
      and/or to support viral RNA synthesis was assayed. Substitution of the 3'-UTR of
      poliovirus RNA with the equivalent sequences of HAV RNA abrogated viral RNA
      replication, whereas the introduction of extended 'foreign' sequences between the
      open reading frame and the 3'-UTR was well tolerated. Point mutation that either
      destabilized the stem-and-loop structure or altered the sequence of the loop in
      domain 'Y' (nomenclature as per Pilipenko et al., [Nuclei Acids Res. 20 (1992)
      1739-1745]) abolished both the infectivity and viral RNA synthesis. These were
      not restored by compensatory mutation that reconstructed the native secondary
      structure of this domain, suggesting that the secondary/tertiary folding of the
      3'-UTR is not the only determinant for template recognition at initiation of RNA
      synthesis, but rather that a specific primary sequence is indeed required.

PMID- 7589566
TI  - The transmembrane gradient of the dielectric constant influences the DPH lifetime
      distribution.
AB  - The fluorescence lifetime distribution of 1,6-diphenyl-1,3,5-hexatriene (DPH) and
      1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) in egg
      phosphatidylcholine liposomes was measured in normal and heavy water. The lower
      dielectric constant (by approximately 12%) of heavy water compared with normal
      water was employed to provide direct evidence that the drop of the dielectric
      constant along the membrane normal shifts the centers of the distribution of both
      DPH and TMA-DPH to higher values and sharpens the widths of the distribution. The
      profile of the dielectric constant along the membrane normal was not found to be
      a linear gradient (in contrast to [1]) but a more complex function. Presence of
      cholesterol in liposomes further shifted the center of the distributions to
      higher value and sharpened them. In addition, it resulted in a more gradient-like
      profile of the dielectric constant (i.e. linearization) along the normal of the
      membrane. The effect of the change of dielectric constant on the membrane
      proteins is discussed.

PMID- 7589567
TI  - Quantification of aminopeptidase N mRNA in T cells by competitive PCR.
AB  - The aminopeptidase N (CD13, EC 3.4.11.2) is a well-characterized surface molecule
      expressed in a variety of cell types and species. Recent data indicate an
      expression of the APN mRNA and the corresponding aminopeptidase activity in human
      peripheral T cells and related cell lines as well. Here, the sensitive method of
      competitive PCR was used to quantify low amounts of APN mRNA in T cell lines. An
      APN cDNA fragment enshortened by a deletion of 87 bp was used as an internal APN
      specific standard. The myelo-monocytic cell line U937 and the lymphoid T cell
      lines HuT78 and H9 contain 2.3 x 10(7), 5.9 x 10(6) and 5.6 x 10(6)
      copies/micrograms total RNA, corresponding to 160, 70 and 50 copies/cell,
      respectively. These data have been confirmed by determination of the APN
      activity, that represents a fraction only of the total cellular neutral
      aminopeptidase activity in hematopoetic cells. In the case of the CD13-positive
      cell line U937, approximately 60-70% of the total neutral aminopeptidase activity
      could be attributed to APN. In contrast, only a minor fraction (5-20%) of the
      cellular neutral aminopeptidase activity in the T cell lines H9 and HuT78
      represents APN. The results suggest that APN gene expression within the
      hematopoetic system is not restricted to myelo-monocytic cells, instead a low APN
      expression may be a common feature of lymphocytes, at least of T cells, too.

PMID- 7589565
TI  - Calbindin28kDa and calbindin30kDa (calretinin) are substantially localised in the
      particulate fraction of rat brain.
AB  - Calbindin28kDa is implicated in cytosolic calcium transport and calciprotection
      functions, principally as a mobile calcium buffer. Using immunoblotting, we have
      found that 36% of total calbindin28kDa is in the particulate fraction of rat
      brain. Particulate calbindin28kDa was located both within and outside organelles
      and required detergent for solubilisation. Equivalent observations were made for
      calbindin30kDa, 27% of which was insoluble. These findings indicate that a
      substantial proportion of calbindin does not function as a mobile calcium buffer,
      and perhaps instead has a calcium signalling role through target ligands in the
      insoluble cellular fraction.

PMID- 7589560
TI  - Does calmitine, a protein specific for the mitochondrial matrix of skeletal
      muscle, play a key role in mitochondrial function?
AB  - The effect of the myotoxic drug chlorpromazine was studied in vitro on proteins
      of sarcoplasmic reticulum and mitochondrial matrix of skeletal muscle in the
      normal mouse. Our results indicate that the drug is specific for calcium-binding
      proteins (calcium ATPase, calsequestrin and calmitine). Its proteolytic effect on
      these proteins, apparently due to the stimulation of specific proteases, could
      account for its myotoxic action. Moreover, calsequestrin (sarcoplasmic reticulum)
      and calmitine (mitochondrial matrix) were not sensitive to the same proteases.
      Proteases acting on calmitine were inhibited by alpha 2-macroglobulin but not
      those acting on calsequestrin. Despite some similarities between these two
      proteins, their characteristics of localization and sensitivity of their
      proteases indicate that calmitine has a specificity within the mitochondrial
      matrix and very probably plays a major role in the mitochondrial regulation of
      free calcium, which controls the activity of various enzymes of the mitochondrial
      matrix involved in ATP synthesis.

PMID- 7589568
TI  - Cinnamate 4-hydroxylase from Catharanthus roseus, and a strategy for the
      functional expression of plant cytochrome P450 proteins as translational fusions
      with P450 reductase in Escherichia coli.
AB  - A PCR-based approach was used to isolate cDNAs for cinnamate 4-hydroxylase (C4H)
      from Catharanthus roseus cell cultures. The protein shared 75.9% identity with
      C4H from other plants, and the transcription was induced under various stress
      conditions. The cloned protein was used to investigate the functional expression
      of plant P450/P450-reductase fusions in E. coli. Fusions containing a modified N
      terminal membrane anchor were located in the membrane and possessed C4H activity
      without solubilization or addition of other factors. The results indicate that
      the fusion protein strategy provides a useful tool to analyze the activities
      encoded in the rapidly increasing number of plant P450 sequences of uncertain or
      unknown function. We also discuss critical elements of the strategy: the choice
      of the E. coli host strain, the N-terminal membrane anchor, and the conditions
      for protein expression.

PMID- 7589569
TI  - Molecular characterization of an Arabidopsis thaliana cDNA encoding a novel
      putative adenylate translocator of higher plants.
AB  - We have isolated an Arabidopsis thaliana cDNA encoding a highly hydrophobic
      membrane protein of 589 amino acids which contains 12 potential transmembrane
      helices and shows a high degree of similarity (43.5% identity, 66.2% similarity)
      to the ATP/ADP translocase of the Gram-negative bacterium Rickettsia prowazekii,
      an obligate intracellular parasite responsible for the epidemic typhus. This
      rickettsial translocator resides in the cytoplasmic membrane and allows the
      bacterium to exploit the host cytoplasmic ATP pool. We hypothesize that the A.
      thaliana homolog of the R. prowazekii ATP/ADP translocase is the functional
      eukaryotic equivalent and resides in the plastid inner envelope membrane where it
      functions as an ATP importer.

PMID- 7589570
TI  - Expression of a chimeric, cGMP-sensitive regulatory subunit of the cAMP-dependent
      protein kinase type I alpha.
AB  - To study the fluctuations of cGMP in living cells through changes of energy
      transfer of dissociable fluorescence labeled subunits, we constructed a cGMP
      sensitive probe by combining the N-terminus of the type I regulatory subunit of
      cAMP-dependent protein kinase (PKA) with the cGMP binding sites of cGMP-dependent
      protein kinase I alpha (PKG). This chimeric regulatory subunit retained PKA-like
      dimerization and PKG-compatible cGMP binding constants (Kd = 53 nM) for both
      binding sites. High affinity interaction with the PKA catalytic subunit was
      verified by Surface Plasmon Resonance (Kd = 3.15 nM). Additionally, the chimera
      inhibits the formation of wild-type holoenzyme with an apparent Ki of 1.05 nM.
      Furthermore, cGMP dissociated the mutant holoenzyme with an apparent activation
      constant of 146 nM. Thus, our construct provides all the requirements needed to
      investigate changes in intracellular cGMP concentrations.

PMID- 7589572
TI  - Terminal deoxynucleotidil transferase is a nuclear PKC substrate.
AB  - Protein phosphorylation is the regulatory mechanism of many cellular events in
      response to changes in metabolic activity and environmental conditions. Seeing
      that PKC and TdT levels in cells are both regulated by PMA, we sought
      particularly intriguing to investigate TdT phosphorylation in vivo, utilizing KM
      3 cells, a TdT-positive human pre-B cell line treated with PMA and in vitro,
      employing purified PKC and human recombinant TdT. Our data show that TdT is a
      substrate for PKC activity, suggesting that TdT phosphorylation could play a key
      role in the pathway affecting the control of gene transcription and protein
      synthesis during lymphoid cells differentiation.

PMID- 7589571
TI  - Isolation, characterization and structure of subtilisin from a thermostable
      Bacillus subtilis isolate.
AB  - A serine protease has been isolated and characterized from Bacillus subtilis,
      strain RT-5 (a thermostable soil isolate from the Tharparkar desert of Pakistan)
      able to grow at 55 degrees C. The primary structure was established by a
      combination of protein and DNA-sequence analyses. The amino-acid sequence,
      inhibition pattern and solubility properties identify the enzyme as a subtilisin.
      It has 43 amino-acid replacements toward subtilisin BPN' and as much as 83
      replacements toward another subtilisin, confirming that strain variabilities are
      extensive between different subtilisin forms. However, the structure is identical
      to one of unknown functional properties deduced from DNA and is closely related
      to mesentericopeptidase but that homologue is not thermostable. From comparisons
      with that form and with subtilisin BPN', it is concluded that replacements of Ala
      --> Ser at positions 85 and 89, Ser --> Ala at position 88 and Asp or Ser --> Asn
      at position 259 may promote thermostability.

PMID- 7589573
TI  - EPR studies of wild-type and several mutants of cytochrome c oxidase from
      Rhodobacter sphaeroides: Glu286 is not a bridging ligand in the cytochrome a3-CuB
      center.
AB  - Wild-type and several mutants of cytochrome c oxidase from Rhodobacter
      sphaeroides were characterized by EPR spectroscopy. A pH-induced g12 signal, seen
      previously in mammalian cytochrome oxidase and assigned to the presence of a
      bridging carboxyl ligand in the bimetallic cytochrome a3-CuB site, is found also
      in the bacterial enzyme. Mutation of glutamate-286 to glutamine inactivates the
      enzyme but does not affect this signal, demonstrating that the carboxyl group of
      this residue is not the bridging ligand. Three mutants, M106Q, located one helix
      turn below a histidine ligand to cytochrome a, and T352A as well as F391Q,
      located close to the bimetallic center, are shown to affect dramatically the low
      spin heme signal of cytochrome a. These mutants are essentially inactive,
      suggesting that these three mutations result in alterations to cytochrome a that
      render the oxidase non-functional.

PMID- 7589574
TI  - Synergistic induction of monocyte chemoattractant protein-1 (MCP-1) by platelet
      derived growth factor and interleukin-1.
AB  - Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the
      recruitment of monocytic cells to the site of inflammation. Resting mesangial
      cells express barely detectable levels of MCP-1 mRNA. Treatment of rat mesangial
      cells with platelet products PDGF-AB, PDGF-BB or serotonin transiently induced
      MCP-1 expression with a maximum after 2 to 4 h and a decline to baseline after 6
      to 8 h. Different kinetics were observed with interleukin-1 beta (IL-1 beta),
      which induced a long lasting elevation of MCP-1 mRNA for more than 20 h.
      Together, PDGF and IL-1 beta synergistically induced MCP-1 expression. The effect
      was most obvious after 16 to 20 h, when induction by PDGF alone had already
      faded, but still PDGF strongly enhanced IL-1 beta-induced MCP-1 mRNA expression.
      MCP-1 mRNA levels were regulated by changes in the stability of the mRNA:
      inhibition of protein synthesis by cycloheximide by itself induced MCP-1 mRNA
      expression and led to superinduction in the presence of PDGF. Message
      stabilization also contributed to the synergistic action of PDGF and IL-1 beta:
      the apparent half life of MCP-1 mRNA determined in the presence of actinomycin D
      was prolonged when both stimuli were added together. We could thus show that in
      mesangial cells different types of cytokines and growth factors synergize to
      enhance MCP-1, the secretion of which could lead to the recruitment of monocytic
      cells into the inflamed mesangium.

PMID- 7589575
TI  - Comparison of the structures of the endothelin A receptor antagonists BQ123 and N
      methyl leucine BQ123 with the crystal structure of the C-terminal tail of
      endothelin-1.
AB  - The functionally important regions of the cyclic pentapeptide endothelin A
      receptor antagonist BQ123 are shown to correlate with the structure of the C
      terminal tail of endothelin-1, as found in the recently-determined X-ray crystal
      structure. Residues 18 and 21 of endothelin-1 are spatially juxtaposed such that
      they superpose extremely well with D-Asp and D-Trp of the antagonist, consistent
      with the residues on this surface of the endothelin helix being important for
      binding. This study provides new information on the three-dimensional nature of
      the endothelin A receptor binding site which may prove useful for rational drug
      design.

PMID- 7589576
TI  - Studies of specific gene induction during apoptosis of cell lines conditionally
      immortalized by SV40.
AB  - Inactivation of SV40 large T antigen in cells immortalized with conditional
      mutants leads to activation of p53 and apoptosis. We have analysed during this
      process the expression of genes induced by p53 or differentially expressed during
      apoptosis in other systems. We find an early induction of Waf1/Cip1. We also
      observe clusterin is induced during the process and displays a high level of
      expression in non-apoptotic cells, suggesting a protective role for clusterin.
      Other genes associated with thymocyte and lymphocyte apoptosis are not induced,
      showing that the pattern of gene induction is specific to the system studied.

PMID- 7589577
TI  - NMR-titrations with complexes between ds-DNA and indole derivatives including
      tryptophane containing peptides.
AB  - It is shown that NMR titrations can be used on a quantitative basis to derive
      binding constants and binding modes of ds-DNA ligand complexes from several
      signals. The results are partially at variance with literature conclusions; they
      can be interpreted by additive and independent contributions of electrostatic
      interactions between DNA phosphate and ammonium centers in the side chain of the
      ligands, and of very weak stacking contributions of the indole rings. While
      gramine and tryptamine are found to intercalate, tryptophane-containing peptides
      do so only, if the tryptophane is flanked by at least two lysine units.

PMID- 7589579
TI  - Nitric oxide synthase inhibitors protect rat retina against ischemic injury.
AB  - Elevation of the ocular pressure in the anterior chamber of the rat eye caused
      major ischemic damage, manifested as changes in retinal morphology. The two most
      affected structures were the inner plexiform layer, which decreased in thickness
      by 90%, and the number of ganglion cells, which decreased by 80%. Pretreatment of
      the animals with N omega-nitro-L-arginine, a nitric oxide (NOS) inhibitor, almost
      completely abolished the ischemic damage. Administration of aminoguanidine, a NOS
      inhibitor selective for the inducible enzyme, partially abolished the ischemic
      damage. Moreover, administration of the NOS inhibitors 1 h after ischemia, also
      protected the retina from damage, suggesting that similarly acting drugs could be
      used clinically to limit ischemic injury in humans. We conclude that NOS, and
      therefore NO, may be involved in the mechanism of ischemic injury to the retina.

PMID- 7589580
TI  - Calcium-dependent binding of uteroglobin (PCB-BP/CCSP) to negatively charged
      phospholipid liposomes.
AB  - To investigate interactions between the polychlorinated biphenyl-binding protein
      uteroglobin and phospholipids, we used a liposome-pelletting assay. PCB
      BP/uteroglobin bound to liposomes made from negatively charged phospholipids
      (PtdSer and PtdIns) in the presence of 5 mM calcium. No binding to liposomes made
      from phospholipids without net charge (PtdChol and PtdEtn) was observed, nor
      could we detect binding in the absence of calcium or when magnesium was
      substituted for calcium. This suggests that PCB-BP/uteroglobin can bind to
      phospholipids in vivo and may have a role in the phospholipid homeostasis of the
      airway and/or secretory pathway of the Clara cell.

PMID- 7589581
TI  - The catalytic activity of Src-family tyrosine kinase is required for B cell
      antigen receptor signaling.
AB  - The Src family protein-tyrosine kinases (PTKs) are known to be important for B
      cell antigen receptor (BCR) signaling. To study the mechanism of action of Src
      PTK in BCR signaling, kinase deficient- and Src homology 2 (SH2)-mutants of Src
      PTK were transfected into Lyn-deficient B cells and analyzed. Kinase activity of
      Src-PTK was essential for tyrosine phosphorylation of Syk and calcium
      mobilization upon receptor ligation, whereas these events were not affected by
      the mutation of SH2 domain. Receptor-mediated tyrosine phosphorylation of Lyn was
      still observed in Syk-deficient B cells. These results demonstrate that the BCR
      induced phosphorylation of Src-PTK is independent of Syk and that the kinase
      activity of Src-PTK is critical for BCR signaling.

PMID- 7589582
TI  - The sensitivity of AMPA-selective glutamate receptor channels to pentobarbital is
      determined by a single amino acid residue of the alpha 2 subunit.
AB  - Clinical concentrations of pentobarbital inhibit the alpha-amino-3-hydroxy-5-
      methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor (GluR)
      channels. Recently, the AMPA-selective GluR channels that contained the alpha 2
      subunit were shown to be more sensitive to pentobarbital block than those without
      the alpha 2 subunit. Here we demonstrated that replacement by glutamine of the
      arginine residue in putative transmembrane segment M2 of the alpha 2 subunit
      (mutation alpha 2-R586Q) drastically reduced the pentobarbital sensitivity of the
      alpha 2 heteromeric channel to the level comparable to those of the alpha 1 and
      alpha 2-R586Q homomeric channels. These results suggest that the arginine residue
      in segment M2 of the alpha 2 subunit is the critical determinant of the
      sensitivities of the AMPA-selective GluR channels to pentobarbital.

PMID- 7589578
TI  - Expression of utrophin and its mRNA in denervated mdx mouse muscle.
AB  - Utrophin is a large cytoskeletal protein which shows high homology to dystrophin.
      In contrast to the sarcolemmal distribution of dystrophin, utrophin accumulates
      at the postsynaptic membrane of the neuromuscular junction. Because of its
      localization within this compartment of muscle fibers, expression of utrophin may
      be significantly influenced by the presence of the motor nerve. We tested this
      hypothesis by denervating muscles of mdx mouse and monitoring levels of utrophin
      and its mRNA by immunofluorescence, immunoblotting and RT-PCR. A significant
      increase in the number of utrophin positive fibers was observed by
      immunofluorescence 3 to 21 days after sectioning of the sciatic nerve.
      Quantitative analyses of utrophin and its transcripts in hindlimb muscles
      denervated for two weeks showed only a moderate increase in the levels of both
      utrophin (approximately 2-fold) and its transcript (approximately 60 to 90%). The
      present data suggest that although utrophin is a component of the postsynaptic
      membrane, its neural regulation is distinct from that of the acetylcholine
      receptor.

PMID- 7589583
TI  - The protein kinase C activator TPA modulates cellular levels and distribution of
      E-cadherin in HT-29 human intestinal epithelial cells.
AB  - The importance of E-cadherin protein in the establishment and maintenance of
      homotypic contacts in epithelial cells has already been determined. We report
      here that the association of E-cadherin to cytoskeleton, required for the
      functionality of this protein, increases progressively after seeding; in HT-29 M6
      cells 4-5 days were required for detecting most of E-cadherin in the Triton X-100
      insoluble (cytoskeleton-associated) fraction. The phorbol ester TPA differently
      affected E-cadherin levels in HT-29 M6 cells; at day 2-3, when most E-cadherin
      was found not-associated to the cytoskeleton, very important decreases (90%) in
      the total levels of this protein were detected as soon as 6 h after the addition
      of this compound. However, on later days (day 5), the predominant effect by 6 h
      was a translocation from the Triton-insoluble to the soluble fraction. The E
      cadherin-associated proteins alpha-catenin and beta-catenin were not
      significantly affected by treatment with TPA.

PMID- 7589586
TI  - Soft tissue sarcoma--messages from completed randomized trials.

PMID- 7589584
TI  - Expression, purification, and characterization of the cGMP-dependent protein
      kinases I beta and II using the baculovirus system.
AB  - Detailed studies of differences in distinct cGMP kinase isoforms are highly
      dependent on expression of large amounts of these enzyme isoforms that are not
      easily purified by conventional methods. Here cGMP-dependent protein kinases, the
      type I beta soluble form from human placenta, and the type II membrane-associated
      form from rat intestine, were each expressed in a baculovirus/Sf9 cell system and
      purified in milligram amounts by affinity chromatography. The expressed
      recombinant proteins displayed characteristics like those of their native
      counterparts. cGK I beta was expressed as a 76 kDa protein predominantly found in
      the cytosol fraction, whereas cGK II was expressed as an 86 kDa protein
      predominantly associated with the membrane fraction. The apparent Ka and Vmax of
      cGMP for activation of cGK I beta were 0.5 microM and 3.4 mumol/min/mg, and for
      cGK II were 0.04 microM and 1.8 mumol/min/mg.

PMID- 7589587
TI  - Soft tissue sarcomas--what is currently being done.

PMID- 7589585
TI  - DNA photocleavage by novel intercalating 6-(2-pyridinium)phenanthridinium
      viologens.
AB  - A new type of DNA-intercalating viologen dications, derived from the N,N'-dialkyl
      6-(2-pyridyl)phenanthridine structure (in which dialkyl is -CH2CH2-,-CH2CH2CH2-,
      or (-CH3)2, abbreviated dq2pyp, dq3pyp, and Me2pyp, respectively), are able to
      produce frank strand breaks in supercoiled plasmid DNA upon irradiation with
      visible light. The amount of photocleavage is similar for the three drugs. The
      observed DNA photosensitization appears to follow a single-strand cleavage model,
      as shown by a kinetic analysis of the reaction with dq2pyp. The photodynamic
      action of the drugs seems to be initiated by a light-induced electron transfer
      reaction from the nucleobases, given the singlet excited-state redox potentials
      (ca. + 2.1 V vs. SHE) and the low quantum yields of singlet molecular oxygen
      production of the drugs (0.1-0.2 in aerated D2O).

PMID- 7589589
TI  - Total thyroidectomy in the treatment of thyroid cancer.
AB  - Considerable controversy exists about the most appropriate treatment for thyroid
      cancer. In this report the authors present their experience of 189 patients, all
      of whom had a total thyroidectomy between June 1980 and December 1993. The age of
      the patients ranged from 11 to 78 years (mean age: 42 years), there were 144
      women and 45 men. Histological types were: 146 papillary, 16 medullary, 10
      follicular, eight Hurtle, six insular and three undifferentiated. Coexistent
      lesions included: 22 thyroiditis, 17 adenomas, one Graves' disease and 22 benign
      goitre. Fifty-six (29.6%) patients had multifocal papillary cancer (bilateral in
      45 cases). Surgical complications included 20 cases of transient recurrent
      laryngeal nerve palsy, 16 cases of transient and one of permanent
      hypoparathyroidism, and one respiratory obstruction due to bilateral recurrent
      laryngeal nerve palsy that required temporary tracheostomy. Two patients were
      reoperated on due to bleeding. Ninety per cent of patients were discharged within
      3 days of thyroidectomy. One hundred and fifty patients were evaluated for 131I
      treatment by a standardized dosimetry procedure 4 weeks after surgery. Dosimetry
      was also used to calculate therapeutic 131I doses. Seventy-six patients did not
      show a 131I uptake above background levels, 56 underwent therapeutic 131I, while
      in the 18 patients who showed an abnormal uptake of 131I it was decided not to
      give the therapeutic dose. The authors conclude that total thyroidectomy can be
      performed with a minimum of permanent disability in patients with malignant
      thyroid tumours. The theoretical and practical advantages of this kind of
      surgical strategy make it the treatment of choice for thyroid cancer.

PMID- 7589588
TI  - Soft tissue sarcoma therapy: prospects for future studies.

PMID- 7589590
TI  - Prognostic factors of thymomas.
AB  - Thymomas are uncommon tumours. This study analyses the prognostic value of
      certain clinical variables and of two different histological classifications.
      Thirty cases were analysed; 24 were women and six men, with a mean age of 50
      years (range 22-69). The pre-operative study included: clinical data (Masaoka's
      and Osserman's clinical classification); chest radiography; and computed axial
      tomography. Surgery was divided into three categories: total tumour resection,
      partial resection and biopsy alone. For the pathological study we followed Salyer
      Eggleston and Marino-Muller classifications. Follow-up averaged 5.5 years (range:
      2-11). As a statistical method we used Kaplan-Meier's survival curves and Cox's
      regression model. Eleven of the patients had associated myasthenia gravis, this
      being the most common clinical type. Age, sex, association with myasthenia
      gravis, surgical technique and Salyer-Eggleston's classification showed no
      prognostic value; conversely, clinical staging and Marino-Muller's classification
      had a high prognostic value. The first treatment that should be considered is
      surgery, with an attempt to perform total tumour resection. Myasthenia gravis did
      not modify the prognosis of the disease. The factors of greatest prognostic
      significance were clinical staging and Marino-Muller's histological
      classification.

PMID- 7589592
TI  - Aggressive basal cell carcinoma of head and neck areas.
AB  - Among skin cancers, basal cell carcinoma (BCC) is considered as a relatively
      indolent disease. Sometimes, these carcinomas have an unusual clinical behaviour,
      with extreme aggressiveness. Based on reports of eight cases of aggressive BCC of
      the head and neck areas, and after a review of the literature, we define three
      criteria of aggressiveness: (1) initial diameter greater than 1 cm, (2) more than
      two recurrences despite all tentative conclusions of adequate treatment, or (3)
      extension into any extracutaneous structure.

PMID- 7589591
TI  - Palliative intra-arterial (i.a.) chemotherapy with carboplatin (CBDCA) and 5-FU
      in unresectable advanced (stage III and IV) head and neck cancer using
      implantable port-systems.
AB  - Intra-arterial drug therapy for head and neck cancer has been used for over 30
      years. Owing to catheter-related complications occurring quite frequently this
      method was abandoned in many institutions. However, the development of
      subcutaneously implantable injection ports has renewed interest in regional drug
      delivery. A total of 19 injection ports have been implanted in 17 patients
      suffering from advanced or recurrent head and neck cancer. Regional chemotherapy
      was well tolerated; the predominant side effects were hemialopecia and mild
      unilateral mucositis. Therefore, regional, intra-arterial chemotherapy using
      implantable injection ports should be considered for palliative treatment of
      advanced head and neck cancer.

PMID- 7589593
TI  - Depressive symptomatology of post-menopausal breast cancer patients: a comparison
      of women recently treated by mastectomy or by breast-conserving therapy.
AB  - The aim of this study was to detect differences in depressive symptomatology in
      post-menopausal breast cancer patients who had recently undergone either
      mastectomy or breast conserving therapy. We measured depressive symptoms shortly
      after diagnosis and surgery as well as 6 months later. There were no significant
      differences in mean scores and relative risk estimates between the two treatment
      groups at either time of measurement. From this study we conclude that women
      treated by breast-conserving therapy have comparable levels of depressive
      symptoms to women treated by mastectomy during the first 8 months after
      diagnosis. Breast-conserving therapy can have cosmetic and physical advantages,
      but requires as much psychological adjustment as mastectomy does.

PMID- 7589594
TI  - Pre-treatment serum levels of tumour markers in metastatic breast cancer: a
      prospective assessment of their role in predicting response to therapy and
      survival.
AB  - The value of pre-treatment serum tumour marker levels in 85 consecutive patients
      of newly diagnosed metastatic breast cancer was prospectively assessed for
      predicting response to therapy and survival. The markers studied were
      carcinoembryonic antigen (CEA), orosomucoid (ORO), erythrocyte sedimentation rate
      (ESR), C reactive protein (CRP), ferritin (FERR), human milk fat globule membrane
      1 and 2 (HMFG1 and 2), CA 15-3 and NCRC-11. There was no correlation between
      serum marker levels and response to therapy. Only serum concentrations of CRP (P
      = 0.02), FERR (P = 0.001), HMFG1 (P = 0.004) and HMFG2 (P = 0.04) were predictive
      for survival. The prognostic significance of HMFG1 was restricted to a minority
      of patients (7%) with extreme values of these serum markers.

PMID- 7589595
TI  - Hepatectomy for liver metastases from breast cancer.
AB  - Thirty-two selected patients underwent laparotomy in an attempt to resect one or
      more isolated liver metastases (LM) from breast cancer. Only 21 of them had
      hepatectomy and systematic lymph node picking of the hepatic pedicle. In six
      patients (19%), the discovery of diffuse metastatic disease contraindicated
      hepatectomy and in five patients (16%), the diagnosis of LM was erroneous, for
      lesions proved to be benign liver tumours. Nineteen of the resected cases
      received preoperative chemotherapy, 12 received post-operative chemotherapy and
      two had repeated hepatectomy. Eight patients (38%) had more than one LM and (24%)
      had positive hepatic lymph nodes. No post-operative mortality occurred. After the
      beginning of this combined treatment, median survival was 38.2 months and 2- and
      5-year survival rates were, respectively, 78% and 24%. After the hepatectomy,
      median survival was 26 months and 2- and 5-year survival rates were,
      respectively, 50% and 9%. When a recurrence did occur (mean time to recurrence
      after hepatectomy was 14.8 months) the liver was involved in 75% of the cases and
      was the first place of recurrence in 56% of the patients. In this limited series,
      the number of LM, the number of positive pedicular lymph nodes, and a response to
      preoperative chemotherapy were not significant prognostic factors. However,
      patients with negative nodes tended to have a better prognosis, as did those with
      the first and only site of relapse being the liver. These selected patients,
      treated with hepatectomy, had a median survival at least three-fold that of
      patients treated with standard, non-surgical treatment. However, hepatectomy
      appeared to be mainly a cytoreductive procedure, and the efficiency of this
      combined treatment was mainly hampered owing to the inefficacy of current
      chemotherapy programmes. Only a prospective randomized study, in well-defined
      patients with isolated LM from breast cancer, comparing conventional treatment
      with or without hepatectomy, will demonstrate whether hepatectomy does indeed
      increase survival rates.

PMID- 7589596
TI  - The outcome of surgery for colorectal cancer in the elderly: a 12-year review
      from the Trafford Database.
AB  - In this database study of 882 patients with colorectal cancer, elderly patients
      are of poor physical status on admission and are more likely to be either
      completely inoperable or require urgent surgery. The operative mortality rate is
      higher and hospital stay is likely to be longer. However, if the elderly patient
      is fit for surgery, survives for more than 30 days and a curative resection
      performed, the 5-year survival and post-operative complication rates are as good
      as those patients in the younger age groups.

PMID- 7589597
TI  - Contribution of PET in the diagnosis of recurrent colorectal cancer: comparison
      with conventional imaging.
AB  - The clinical value of total body PET with FDG was evaluated in 76 patients
      presenting with or suspected of recurrent local or distant colorectal cancer. PET
      results were compared to those of routine imaging (CT pelvis, CT/US liver and
      CXR). The accuracy of PET for local disease was 95% which was superior to CT
      pelvis (accuracy 65%). PET accuracy for liver metastases (98%) compared
      favourably to CT/US-liver accuracy (93%). Unexpected extra-hepatic mestastases
      were detected by PET in 14 locations in 10 patients. Also, a primary breast
      cancer was found in one patient. The main value of PET appeared an improved
      staging of apparently resectable, local or distant recurrent disease. Thereby, a
      more adequate indication of major secondary surgery could be attained.

PMID- 7589599
TI  - Effect of ranitidine and low-dose interleukin-2 in vitro on NK-cell activity in
      peripheral blood from patients with liver metastases from colorectal cancer.
AB  - Peripheral venous blood from 12 patients with colorectal cancer and eight healthy
      volunteers was used to identify the lowest in vitro dose of human, recombinant
      interleukin-2 (rIL-2) with immunoactivity on NK-cell lysis of K562 tumour cells.
      Subsequently, this dosage of 200 units/ml rIL-2, which may respond to 10(6) units
      in vivo, was used alone or in combination with ranitidine (0.02 mg/ml, which may
      correspond to 100 mg in vivo) to improve in vitro NK-cell activity in peripheral
      blood from 25 patients with liver metastases from colorectal cancer. A standard 4
      hour Cr51-release assay of K562 tumour cells was used for the analyses.
      Spontaneous NK-cell activity was 19.0% (6.5-33.2), while ranitidine-induced NK
      cell activity was 23.6% (7.8-46.2), and without statistical difference from
      spontaneous activity. Recombinant IL-2-induced NK-cell activity was 37.1% (11.1
      71.7) (P < 0.05 compared to spontaneous activity), and rIL-2 plus ranitidine
      induced NK-cell activity was 52.7% (18.9-85.6) (P < 0.05 compared to spontaneous
      and to rIL-2-induced activity, respectively). These results suggest a synergistic
      increase of low-dose rIL-2-induced NK-cell activity by ranitidine. Therefore, the
      combination of low-dose rIL-2 and ranitidine may be beneficial to improve post
      operative immune competence, and should be considered in future adjuvant
      treatment regimens of cancer patients.

PMID- 7589598
TI  - A randomized trial of cimetidine with 5-fluorouracil and folinic acid in
      metastatic colorectal cancer.
AB  - Cimetidine has demonstrated a survival benefit in a randomized trial as adjuvant
      therapy for gastric cancer. We have demonstrated expression of histamine
      receptors on colon cancer cell lines and inhibition of their growth with
      cimetidine. Cimetidine also activates suppressor T cells and stimulates cell
      mediated immunity. We therefore performed a randomized controlled clinical trial
      to determine the effect of cimetidine 400 mg given twice daily in conjunction
      with chemotherapy vs chemotherapy alone. Thirty-eight patients were randomized
      and 35 patients were eligible for further analysis. Both groups were well matched
      for pre-treatment characteristics. There was no difference in overall response.
      There was, however, a significantly increased rate of CEA response in the
      cimetidine group. Four of 11 patients (36%) in the cimetidine group had a CEA
      response compared to none of eight in the control. Meaningful comparisons of
      overall survival cannot yet be made. This study demonstrates that cimetidine has
      encouraging activity in increasing CEA response in patients with metastatic
      colorectal cancer treated with chemotherapy. This observation needs to be
      extended in a larger randomized study, which is currently underway.

PMID- 7589601
TI  - Treatment of non-resectable pelvic malignancies by isolated pelvic perfusion. A
      preliminary study.
AB  - Management of non-resectable pelvic tumours by intra-arterial local chemotherapy
      was shown to be beneficial but systemic toxicity limits its use. To overcome this
      problem isolated pelvic perfusion (IPP) was introduced as an alternative. This
      study summarizes our preliminary experience with IPP in the treatment of 18 non
      resectable pelvic tumours [recurrent rectal adenocarcinoma (six), soft tissue
      sarcoma (STS) (five), bone tumour (three), epidermoid carcinoma (two), prostatic
      adenocarcinoma (one), malignant melanoma (one)]. Results of IPP were regarded as
      complete remission (CR), partial remission (PR), stable disease (SD) and disease
      progression (DP) according to the changes in three parameters including; scoring
      in pain, tumour marker and tumour size measurements. Complete and partial
      remission were established in five (27%) and seven (39%) patients respectively
      indicating a benefit ratio of 66%. Objective pain relief was encountered in 53%
      of the cases. All patients with STS had undergone further surgical treatment
      after IPP with successful curative resections in four. No residual tumour was
      found at the laparotomy of the fifth patient. Presenting symptom of the prostatic
      adenocarcinoma patient was symptomatic hypoglycaemia which resolved completely
      after IPP. To our knowledge, this represents the first case reported in the
      English literature in whom tumour related hypoglycaemia was successfully managed
      by IPP. In conclusion; management of non-resectable pelvic tumours by IPP seems
      to offer serious palliation and increase in the quality of life without any
      systemic toxicity. Our preliminary experience suggests even resectability may be
      achieved in a number of patients especially in those with STS.

PMID- 7589600
TI  - Effect of extended ibuprofen administration on the acute phase protein response
      in colorectal cancer patients.
AB  - The regulation of acute phase protein production and the relationship of the
      acute phase protein response to tumour growth was examined in colorectal cancer
      patients (n = 9). Ibuprofen (1200 mg/d) was administered for 8-11 days. Following
      ibuprofen administration there were reductions in circulating concentrations of C
      reactive protein (P = 0.01), interleukin-6 (P = 0.06), cortisol (P = 0.04) and
      also in the platelet count (P = 0.01). There was no significant change in
      albumin, insulin and carcinoembryonic antigen. These results indicate that
      ibuprofen administered over a prolonged period substantially reduces acute
      protein production via its effect on interleukin-6 and cortisol. It remains to be
      determined whether ibuprofen is useful in moderating tumour growth in colorectal
      cancer patients.

PMID- 7589602
TI  - Histological suggestions of 'paratransformation' in oesophageal squamous cell
      carcinoma.
AB  - We have postulated that oesophageal squamous cell carcinoma arises from
      multifocal areas and not from one cell, and we present the circumstantial
      evidence for field carcinogenesis in oesophageal cancer. Among 290 cases examined
      with oesophageal squamous cell carcinoma, lymphatic permeation or intramural
      metastasis was evident in 110 cases. Of these carcinomatous transformation of the
      epithelium adjacent to either lymphatic vessel permeation or intramural
      metastasis of the squamous cell carcinoma was recognized in six cases. It is
      considered that the cancer tissue either in the lymphatic vessel or intramural
      metastasis promotes a malignant transformation of the squamous epithelium over
      these foci. 'Paratransformation' is therefore thought to be one of the potential
      models of origin for oesophageal squamous cell carcinoma.

PMID- 7589604
TI  - Results of a prospective randomized trial using DTIC and interferon as adjuvant
      therapy for stage I malignant melanoma.
AB  - This prospective randomized trial evaluated the effect of DTIC and interferon as
      adjuvant therapy for high risk stage 1 malignant melanoma in 26 patients. Both
      groups were well matched for depth of disease, site of melanoma and other
      prognostic criteria. Like other studies the findings of 2.6 times increased
      relative risk of mortality in the treatment arm do not support a rationale for
      adjuvant immuno-chemotherapy even in patients at high risk of recurrence.

PMID- 7589605
TI  - Pharmacokinetics of two different delivery regimens of doxorubicin in isolated
      hyperthermic limb perfusion.
AB  - Evaluation of doxorubicin (DOX) pharmacokinetics in hyperthermic isolated limb
      perfusion (HILP) is limited. In this study two administration regimens of DOX
      were compared in terms of area under the time concentration curve (AUC) in
      plasma. HILP was performed in 13 dogs. In group 1 (n = 7) four single doses of
      DOX were injected in intervals of 15 minutes, in group 2 (n = 6) DOX was
      administered continuously during the first 30 min. The total dose in both groups
      was 1 mg/kg body weight, and the perfusion lasted 60 min. Concentrations of DOX
      and its major metabolite doxorubicinol (DOXol) were measured in perfusate and
      muscle tissue by high performance liquid chromatography (HPLC). Pharmacokinetic
      estimates were calculated. The two investigated administration modes provided
      sufficient drug levels of DOX during the whole perfusion time. Maximum
      concentrations in the perfusate and areas under the time concentration curves
      were nearly the same. The tissue concentrations also did not show significant
      differences. Both regimens are practicable avoiding high peak levels of the drug
      in order to minimize toxic side effects.

PMID- 7589603
TI  - Subxiphoidal pericardial 'window' in the management of malignant pericardial
      effusion.
AB  - Over the last 5 years, 26 cancer patients developed pericardial effusion and were
      managed surgically with the creation of a subxiphoidal pericardial 'window'. The
      operation, in the majority of the cases was performed under local anaesthesia
      with adequate sedation. It was found to be safe and easy to perform. The
      operative approach was beneficial to the group of patients without massive
      involvement by tumour of the thoracic cavity with relief of symptoms. Significant
      palliation was achieved for the patients with extensive tumour involvement of the
      mediastinum and thorax, although survival in this group of patients was
      relatively short.

PMID- 7589606
TI  - Update on urology--prostate cancer. 3--Systemic and palliative treatment of
      prostate cancer.

PMID- 7589608
TI  - How would you manage recurrent liposarcoma of the chest wall?
AB  - Summary of the cases presented in full in the August issue (Eur J Surg Oncol
      1995; 21: 424-426 Patient 1. A 46-year-old female presented with a huge benign
      lipoma of the left axilla/breast in 1977. Repeated excisions led to three
      recurrences, the first reported as an intramuscular lipoma, the latter two as
      well-differentiated liposarcoma. She presented in 1990 with a large recurrence
      partially fixed to the chest wall. Patient 2. A 58-year-old man with
      cardiorespiratory impairment due to long-standing valvular disease presented in
      1982 with a large poorly differentiated sarcoma over the lower posterior rib
      cage. He was treated by wide local excision (not including the ribs), and cover
      with a latissimus dorsi flap to allow completion of a radical perioperative
      course of radiotherapy. Recurrences around the periphery of the excision occurred
      in 1984, 1985, 1986, 1987, each treated by relatively wide local excision. He
      presented again in 1989 with further peripheral recurrences attached to the rib
      cage, still without evidence of distant metastasis, at which stage a further plan
      of management was sought.

PMID- 7589607
TI  - Personal surgical experience. The impact of malignant disease on the life and
      practice of surgeons. Malignant myeloma and stem cell transplantation.

PMID- 7589609
TI  - Abdominal wall metastasis and peritoneal carcinomatosis after laparoscopic
      assisted colectomy for colon cancer.
AB  - We report a case of a port-site recurrence with diffuse peritoneal carcinomatosis
      after laparoscopic-assisted right hemicolectomy. The interval between resection
      of the colonic adenocarcinoma and diagnosis of the recurrence was short (1
      month), suggesting that intraperitoneal dissemination and tumour implantation on
      surgical wounds may represent the principal mechanism of recurrence after
      laparoscopic surgery. Review of the literature shows an alarming increase in the
      occurrence of this devastating complication. Although beneficial to the patient
      in the immediate post-operative period, the adequacy of laparoscopic-assisted
      colectomy in tumour is increasingly under question.

PMID- 7589613
TI  - Choriocarcinoma metastatic to the maxillary gingiva.
AB  - A rare metastatic lesion from a gestational trophoblastic neoplasm is presented
      in a 26-year-old woman. The first symptom and sign was mild pain and a mass in
      the gingiva. The diagnosis was established by gingival biopsy. The patient was
      treated with 6 courses of methotrexate, actinomycin D and cyclophosphamide (MAC)
      and has no evidence of disease 2 years after completion of therapy.

PMID- 7589612
TI  - Choriocarcinoma presenting as a breast lump.
AB  - A case of choriocarcinoma in a previously well 32-year-old woman presenting as a
      tender breast lump whilst she is breastfeeding.

PMID- 7589614
TI  - Squamous cell carcinoma of the gallbladder presenting with a biliary-colic
      fistula.
AB  - Pure squamous carcinoma of the gall bladder is a rare tumour which may present
      diagnostic difficulty for the histopathologist. A case presenting as a biliary
      colic fistula is described and the diagnostic histological features discussed.
      Theories regarding aetiology and the prognosis of this rare tumour are also
      discussed.

PMID- 7589610
TI  - Neurofibrosarcoma of the duodenum.
AB  - A case of neurofibrosarcoma of the second part of the duodenum is reported. The
      presenting symptom was upper GI tract bleeding. An emergency
      pancreaticoduodenectomy was performed to remove a 6 x 8 cm tumour invading the
      head of the pancreas and the ampulla of Vater. Histopathologically, a low grade
      malignant neurofibrosarcoma without lymph node invasion was evident. No adjuvant
      therapy was judged to be necessary. The patient is well and free of disease 5
      years following the resection of the neoplasm.

PMID- 7589611
TI  - Surgical treatments for oesophageal cancer concomitant with gastric adenoma with
      severe epithelial atypia.
AB  - The various surgical treatments for oesophageal cancer concomitant with gastric
      adenoma with severe epithelial atypia (SEA) are discussed by presenting three
      such cases. As gastric adenoma with SEA had been considered to be a precancerous
      condition but not normally an indication for gastrectomy, we devised an operative
      strategy of laparotomy and thoracotomy. For Case 1, with early oesophageal cancer
      and gastric adenoma with SEA in the body of stomach, a laparotomy and local
      resection of the gastric lesion were carried out prior to thoracotomy in order to
      determine the safest reconstructive method after measuring the length of the well
      nourished gastric tube. In Case 2, with advanced oesophageal cancer, a
      thoracotomy was first performed to assess the curability of surgery for the
      oesophageal cancer and a gastric adenoma was removed. In contrast, for Case 3
      with advanced oesophageal cancer, and in whom post-operative survival was deemed
      to be short, a gastric adenoma was not resected. The most appropriate operative
      methods should thus be decided after careful consideration of the stage of the
      oesophageal cancer and characteristics of the gastric adenoma.

PMID- 7589616
TI  - Mastectomy, lumpectomy, calcifectomy, and lesionectomy.

PMID- 7589615
TI  - Long-term survival in two cases of colorectal carcinoma following a new
      chemotherapy regimen and subsequent metastasectomy.

PMID- 7589617
TI  - Guidelines for surgeons in the management of symptomatic breast disease in the
      United Kingdom.

PMID- 7589618
TI  - Follicular fluid levels of midazolam, fentanyl, and alfentanil during
      transvaginal oocyte retrieval.
AB  - OBJECTIVE: To investigate the time course of changes in follicular fluid (FF)
      concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United
      Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and
      alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal
      oocyte collection. STUDY DESIGN: Forty-five patients with tubal infertility were
      randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for
      sedation during ultrasound-guided transvaginal oocyte collection. Paracervical
      block with lignocaine was given for analgesia. Simultaneous blood and FF samples
      were drawn at 5-minute intervals after the bolus dose for analysis of drug
      levels. RESULTS: Data were obtained on 15 women receiving midazolam and fentanyl
      and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak
      and then fell in an exponential fashion as was expected. The FF levels of the
      agents continued to rise significantly to 25 minutes after the bolus dose,
      although the absolute level was low when compared with the blood level. There
      were no significant differences in fertilization or pregnancy rates in the three
      groups, but patient numbers were small. CONCLUSION: We conclude that midazolam,
      fentanyl, and alfentanil are found in FF after a single IV dose, but further
      investigation needs to be undertaken to investigate any potential influence on
      fertilization and implantation rates.

PMID- 7589619
TI  - Comparison of sperm parameters, in vitro fertilization results, and subsequent
      pregnancy rates using sequential ejaculates, collected two hours apart, from
      oligoasthenozoospermic men.
AB  - OBJECTIVE: To evaluate the effect of second consecutive ejaculate collected 2
      hours after the first one from infertile men on sperm quality and fertilization
      and pregnancy rates (PRs) in IVF. DESIGN: A prospective case-control study.
      SETTING: In vitro fertilization unit of a university hospital. PATIENTS: Thirty
      nine consecutive infertile patients with oligoasthenozoospermia scheduled for IVF
      ET. MAIN OUTCOME MEASURES: Two consecutive ejaculates were obtained 2 hours apart
      and were assessed for volume, sperm count, motility, morphology, and quality of
      swim-up fraction. The subsequent fertilization, cleavage, and PRs (as defined by
      the appearance of intrauterine gestational sac) were compared between the two
      ejaculates. RESULTS: In 28.2% of the individuals the semen analysis of the first
      ejaculate precluded proceeding with IVF. A statistically significant improvement
      was shown in sperm cell motility (31.9% +/- 20.7% versus 15.6% +/- 15.3%) and in
      motile count after swim-up (4.9 +/- 4.5 versus 2.6 +/- 3.1 x 10(6) sperm). No
      improvement could be demonstrated in sperm density or morphology. The volume of
      the second ejaculate was decreased significantly as compared with the first one.
      The fertilization rate, the cleavage rate, and PR were all increased when oocytes
      were exposed to sperm from the second ejaculate compared with oocytes exposed to
      sperm from the first ejaculate. The overall PR in our series was 25.6%.
      CONCLUSIONS: We suggest that in the group of infertile men with
      oligoasthenozoospermia, whose partners are scheduled for IVF-ET, if on the day of
      retrieved oocytes insemination, the ejaculate is of unacceptable quality, a
      second ejaculate collected 2 hours after collection of the initial ejaculate may
      produce a sample that exhibits improvements in both semen parameters and
      reproductive potential.

PMID- 7589621
TI  - Experimental extension of the time interval between oocyte maturation and
      ovulation: effect on fertilization and first cleavage.
AB  - OBJECTIVE: To test the hypothesis that impaired fertility in human patients with
      high LH concentrations throughout the follicular phase of the menstrual cycle
      reflects premature maturation of their oocytes. DESIGN: Previous information that
      resumption of meiosis is induced by lower hCG concentrations than that required
      for stimulation of follicular rupture was confirmed and used for establishment of
      a rat animal model in which oocyte maturation and ovulation can be separated
      experimentally. In further experiments hypophysectomized, pregnant mare serum
      gonadotropin (PMSG)-primed, immature female rats injected with 1.1 IU of hCG, a
      dose found to induce maturation in 72.9% +/- 6% of the rats with no effect on
      ovulation, were administered with a second injection of an ovulatory dose (4 IU)
      of hCG, 24 hours later. The ovulated eggs were subjected to IVF. RESULTS:
      Fertilization and first cleavage in oocytes recovered from our experimental
      animal model were similar to that observed in control PMSG-primed, either
      hypophysectomized or intact rats, treated by a single injection of 4 IU of hCG.
      CONCLUSIONS: The extension of the time interval between oocyte maturation and
      ovulation in the rat does not result in a lower rate of fertilization or a
      reduced incidence of cleavage. However, an inferior developmental capacity of
      these embryos cannot be ruled out.

PMID- 7589620
TI  - Screening for subclinical inflammation in ejaculates.
AB  - OBJECTIVE: To determine the clinical significance of albumin determination in
      ejaculates by means of an easy office test to screen semen samples for
      subclinical infection-inflammation. PATIENTS: One hundred fifty-nine randomly
      chosen males of couples with longstanding infertility (median duration of
      infertility 4 years (range 1 to 19 years) without clinical signs or symptoms of
      genital tract infection. SETTING: Outpatient Infertility Clinic of the University
      of Heidelberg, Germany. MAIN OUTCOME MEASURES: Screening of ejaculates for
      subclinical infection-inflammation by means of a ready-to-use kit for
      semiquantitative detection of albumin in addition to determination of leukocytes
      rates by means of monoclonal antibodies for differentiation of round cells and
      measurement of granulocyte elastase concentration in semen samples. Evaluation of
      sperm quality by means of standard sperm analysis including determination of
      local antisperm antibodies with the mixed antiglobulin reaction, evaluation of
      sperm functional capacity in vitro with the standardized sperm-cervical mucus
      (CM) penetration test, and semen cultures. All tests were performed from aliquots
      of the same ejaculates. RESULTS: Screening of semen samples for elevated albumin
      with the modified paper strips proved to be very easy, quick, and suitable for
      routine use. Positive results were not related markedly to medical history and
      outcome of clinical examination as well as to standard parameters of sperm
      analysis and were not influenced by local antisperm antibodies of the
      immunoglobulin (Ig)G and/or IgA class and microbial colonization. However,
      albumin-positive semen samples were significantly less frequent in case of very
      good outcome of the sperm-CM penetration test. A significant relationship was
      found with high rates of leukocytes of the round cells in semen samples (total
      range 0% to 96%) and the concentration of granulocyte elastase (total range 1 to
      880 micrograms/L). CONCLUSIONS: The results of this prospective study suggest
      that the determination of albumin in semen samples with ready-to-use test kits
      might be a valuable additional marker for subclinical infection-inflammation of
      the male genital tract and therefore suitable for screening during infertility
      investigation.

PMID- 7589622
TI  - A magnetic resonance imaging approach for the diagnosis of a triplet cornual
      pregnancy.
AB  - OBJECTIVES: To describe a rare case of triplet cornual pregnancy after IVF-ET and
      to assess the role of magnetic resonance imaging (MRI) for early diagnosis.
      DESIGN: Case report. SETTING: Infertility and IVF Unit, in an university medical
      center. PATIENT: A 31-year-old healthy patient with a 3-year history of primary
      male infertility. INTERVENTION: Standard IVF-ET treatment cycle, using a GnRH
      agonist (long protocol) and hMG for ovarian stimulation. RESULTS: A cornual
      triplet pregnancy is described with the approach for the diagnosis. Magnetic
      resonance imaging was complementary to endovaginal sonography for early diagnosis
      and permitted a timed conservative management. CONCLUSIONS: When transvaginal
      ultrasound findings did not provide an accurate location of the pregnancy, MRI
      was indicated to confirm the diagnosis.

PMID- 7589623
TI  - No correlation between peritubal and mucosal adhesions in hydrosalpinges.
AB  - OBJECTIVE: To correlate the presence and extent of peritubal and mucosal
      adhesions in hydrosalpinges. DESIGN: Comparative study. SETTING: Tertiary centers
      with experience in tubal microsurgery. PATIENTS: Infertile women with complete
      distal tubal block. INTERVENTION: Salpingoneostomy. MAIN OUTCOME MEASURE:
      Presence and extent of adhesions. RESULTS: Peritubal adhesions occur more
      frequently than mucosal adhesions in hydrosalpinges. Of 7 hydrosalpinges without
      peritubal adhesions, 1 showed mucosal adhesions but of 83 hydrosalpinges with
      peritubal adhesions, 31 (37%) showed no mucosal adhesions. CONCLUSION: Accurate
      endoscopic assessment of the ampullary mucosa is recommended in hydrosalpinx to
      select the appropriate patient for surgery.

PMID- 7589625
TI  - A prospective comparison of Synthetic Serum Substitute and human serum albumin in
      culture for in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To compare the efficacy of a globulin-containing protein source,
      Synthetic Serum Substitute (Irvine Scientific, Santa Ana, CA) and human serum
      albumin (HSA) in the early culture of human oocytes and embryos. DESIGN: Oocytes
      from 31 consecutive IVF cycles were assigned alternately to dishes containing
      human tubal fluid (HTF) and either Synthetic Serum Substitute or HSA as the
      protein source. Each semen sample was split for processing in Synthetic Serum
      Substitute or HSA. Sperm processed in Synthetic Serum Substitute was added to
      oocytes cultured in Synthetic Serum Substitute, and sperm processed in HSA was
      added to oocytes cultured in HSA. After determination of fertilization, zygotes
      were placed in HTF containing the same protein supplement. Before transfer, the
      embryos were graded morphologically. MAIN OUTCOME MEASURES: Occurrence of normal
      fertilization and embryo quality as assessed by morphological grading. RESULTS:
      There was no significant difference in the occurrence of fertilization or in
      embryo morphological quality between oocytes cultured in Synthetic Serum
      Substitute as compared with HSA. CONCLUSIONS: The use of a globulin-containing
      protein source in culture for IVF-ET did not improve the fertilization rate or
      embryo quality. Our design did not allow for demonstration of an effect on
      pregnancy rate.

PMID- 7589626
TI  - Successful establishment of pregnancy by superovulation and intrauterine
      insemination with sperm recovered by a modified Hotchkiss procedure from a
      patient with retrograde ejaculation.
AB  - OBJECTIVE: To improve the quality of the sperm recovered from the bladder in a
      patient with retrograde ejaculation who already had failed to conceive after
      several attempts at IUI with sperm recovered by conventional techniques. SETTING:
      University Hospital. PATIENTS: A couple with male infertility due to retrograde
      ejaculation caused by the Zielke operation, a spinal fixation procedure performed
      to correct severe kyphoscoliosis. INTERVENTION: Superovulation and IUI of sperm
      recovered from the bladder using a modified Hotchkiss procedure involving the
      introduction into the bladder of Earle's balanced salt solution (EBSS) buffered
      with Hepes in sufficient quantity to bring the urinary pH and osmolarity to those
      of fresh ejaculate. MAIN OUTCOME MEASURES: Urine pH and osmolarity at baseline
      and after dilution with EBSS buffered with HEPES. Concentration, motility, and
      progression score of the sperm recovered from the bladder. RESULTS: Good sperm
      samples were achieved. Pregnancy was established when IUI was performed in
      association with superovulation induction. CONCLUSIONS: Determination of urine pH
      and osmolarity appears to be a useful method for choosing the ideal sperm
      recovery procedure. The modified Hotchkiss procedure described seems to be a
      promising alternative method for recovering sperm for artificial insemination.

PMID- 7589624
TI  - The quality of human embryo growth is improved when embryos are cultured in
      groups rather than separately.
AB  - OBJECTIVE: To determine the effect of culturing human embryos in groups on
      cleavage rates, morphology grades, and embryo scores when compared with embryos
      cultured singly. DESIGN: Prospective. SETTING: The IVF-ET program of the
      Pennsylvania State University, Department of Obstetrics and Gynecology, Hershey
      Medical Center, Hershey, Pennsylvania. PATIENTS: Fifty-five infertile women who
      each had at least five zygotes underwent IVF-ET. INTERVENTIONS: Zygotes from each
      patient were allocated to be cultured singly and in groups. MAIN OUTCOME
      MEASURES: Cleavage rate, morphology grade, and embryo score. RESULTS: Grouping
      embryos significantly enhanced cleavage rates and embryo scores but not
      morphology grade as compared with embryos grown singly. Additionally, the size of
      the groups correlated positively with cell number and embryo score but not the
      morphology grade. CONCLUSION: Culturing human embryos in groups enhances the
      quality of their growth by increasing the cleavage rates and embryo scores.
      Because pregnancy rates are improved by transferring embryos with higher embryo
      scores, coculturing human embryos may be a way of enhancing pregnancy rates.

PMID- 7589628
TI  - "Nothing succeeds like success".

PMID- 7589629
TI  - Ethical and legal issues in human embryo donation.
AB  - OBJECTIVE: To identify main ethical and legal issues that arise with donation of
      embryos left over from IVF treatments of infertility or created from separate
      gamete donations. DESIGN: Analysis of ethical commentary, advisory committee
      reports, statutes, court cases, and legal commentary relating to gamete and
      embryo donation and assisted reproduction to assess their effect on donation of
      created or leftover embryos. RESULTS: Donation of surplus embryos or embryos
      created from separate gamete donations would help a subset of infertile couples
      to form families. A program undertaking embryo donation will have to coordinate
      the donation of embryos from its own patients or other programs or arrange for
      separate gamete donations to form embryos. The main ethical issues concern the
      effect on offspring, consent and counseling of donors and recipients, avoidance
      of mixing embryos or gametes from different sources, and payment of donor
      expenses. The main legal issues concern whether embryo donation is viewed as
      gamete donation or adoption; the rearing rights and duties of donors and
      recipients in resulting offspring; liability; and compensation issues; and the
      legality of monetary compensation for donors. Donation of embryos for research
      raises separate issues. CONCLUSION: Human embryo donation is an ethically and
      legally acceptable way for infertile couples to form families.

PMID- 7589630
TI  - The role of the mental health professional in reproductive medicine.

PMID- 7589627
TI  - The relationship between plasma levels of gonadotropins, androgens, and prolactin
      in azoospermic men with their testicular spermatogenic pattern.
AB  - OBJECTIVE: To assess the relationship between plasma levels of gonadotropins,
      androgens, and PRL with testicular spermatogenic pattern. DESIGN: Patient series.
      SETTING: University affiliated medical center. PATIENTS: One hundred twenty
      azoospermic infertile men. INTERVENTIONS: Testicular fine needle aspirations and
      determination of plasma levels of FSH, LH, T, free T, and PRL. MAIN OUTCOME
      MEASURES: Gonadotropins, androgens, and PRL plasma levels as a diagnostic
      criterion of testicular spermatogenic patterns. RESULTS: No statistically
      significant differences were detected in plasma levels of LH, androgens, and PRL
      among patients with Sertoli cell only, spermatogenic arrest, or full
      spermatogenesis. Elevated plasma levels of FSH threefold above the upper normal
      limit preclude, with a probability of 95%, the existence of full testicular
      spermatogenesis, but are not valid for the diagnosis of either Sertoli cell only
      syndrome or spermatogenic arrest. CONCLUSIONS: Luteinizing hormone, androgens,
      and PRL plasma levels are of no diagnostic value in predicting any specific
      spermatogenic pattern, and plasma FSH levels can not be used for diagnosing
      Sertoli cell only syndrome.

PMID- 7589631
TI  - Incidence of symptom recurrence after hysterectomy for endometriosis.
AB  - OBJECTIVES: To determine the relative risk of symptom recurrence and/or
      reoperation after hysterectomy with ovarian preservation for the treatment of
      endometriosis. DESIGN: Historical prospective study of patients with
      endometriosis who underwent hysterectomy with or without ovarian preservation.
      PATIENTS: One hundred thirty-eight women who underwent hysterectomy with the
      diagnosis of endometriosis. METHODS: A computer search identified 138 women who
      underwent hysterectomy with the diagnosis of endometriosis at Johns Hopkins
      Hospital from 1979 to 1991. Follow-up information was obtained from medical
      records, outpatient charts, and telephone surveys. RESULTS: Twenty-nine women had
      hysterectomy with some ovarian tissue preserved; 109 had all ovarian tissue
      removed. Of those with ovarian preservation, 18 of 29 (62%) had recurrent pain
      and 9 of 29 (31%) required reoperation. Of those who had no ovarian preservation,
      11 of 109 (10%) had recurrent symptoms and 4 of 109 (3.7%) required reoperation.
      Ovarian conservation was associated with a relative risk for pain recurrence of
      6.1 (95% confidence interval [CI] 2.5 to 14.6) compared with patients with
      oophorectomy in a Cox proportional hazards model. The relative risk for
      reoperation in patients with ovarian conservation was 8.1 (95% CI 2.1 to 31.3).
      CONCLUSION: Compared with women who had oophorectomy for endometriosis, patients
      who underwent hysterectomy with ovarian conservation had 6.1 times greater risk
      of developing recurrent pain and 8.1 times greater risk of reoperation.

PMID- 7589632
TI  - Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone
      versus goserelin combined with estrogen-progestogen add-back therapy in the
      treatment of endometriosis.
AB  - OBJECTIVE: To investigate whether the addition of low-dose estrogen-P combination
      hormone replacement therapy (HRT) to GnRH agonist (GnRH-a) treatment for
      endometriosis reduces the pharmacologic side effects of such treatment without
      reducing efficacy and to determine the endocrinologic changes during treatment.
      DESIGN: Prospective, randomized, double-blind, placebo-controlled, comparative
      study of two drug regimens: 3.6 mg goserelin acetate in a 28-day SC depot
      formulation once monthly for 6 months plus either a combination of 2 mg 17 beta
      E2 and 1 mg norethisterone acetate (NET) 1 mg or matching placebo tablets once
      daily for 6 months. SETTING: Multicenter study in three tertiary referral centers
      at university teaching hospitals and two central hospitals. PATIENTS: Women with
      laparoscopically confirmed symptomatic endometriosis were included in the study.
      RESULTS: Of the total of 109 patients screened, 93 were recruited and 88 patients
      were randomized to either the HRT or the placebo group. Four women were withdrawn
      because of various medical reasons, and 76 patients were followed-up for a total
      of 12 months. In terms of efficacy, there was no difference between the two drug
      regimens for objective or subjective response. There were significantly less
      postmenopausal symptoms in the patients treated with goserelin plus HRT compared
      with those treated with goserelin plus placebo. CONCLUSION: Goserelin diminished
      significantly the symptoms and laparoscopic scores of endometriosis. The addition
      of HRT did not reduce the efficacy of goserelin but diminished the postmenopausal
      symptoms during treatment.

PMID- 7589633
TI  - Role of major histocompatibility complex class I expression and natural killer
      like T cells in the genetic control of endometriosis.
AB  - OBJECTIVE: To evaluate whether the expression of human leukocyte antigen (HLA)
      class I on eutopic and ectopic endometrial cells modify the susceptibility to
      lysis mediated by lymphocytes. DESIGN: Evaluation of T lymphocyte cytotoxic
      activity and HLA class I expression on endometrial cells. SETTING: Subjects were
      recruited at laparoscopy. PATIENTS: Patients with endometriosis (n = 7). Healthy
      women as controls (n = 10). MAIN OUTCOME MEASURES: Human leukocyte antigen class
      I molecule analysis of endometrial cells was carried out by immunofluorescence
      and flow cytometry. Phenotyping of T lymphocytes was performed to analyze T-cell
      subsets. Cytotoxicity was performed to determine cytolytic activity against
      endometrial cells. RESULTS: In vitro culture of endometrial cells down-regulates
      the expression of HLA class I molecules and enhances the susceptibility to lysis
      mediated by natural killer (NK)-like T lymphocytes. Cytolytic T-cell clones,
      expressing the CD94 antigen, are inhibited by the HLA-B7 allele on endometrial
      cells. Ectopic endometrial cells modulate the expression of HLA class I
      molecules. CONCLUSIONS: The resistance to lysis of endometrial cells is related
      to expression of surface HLA class I molecules, which send a negative signal for
      lysis mediated by NK-like T lymphocytes. The HLA-B7 allele inhibits the cytotoxic
      activity, suggesting that the growth of ectopic endometrial cells might be under
      a genetic control.

PMID- 7589634
TI  - Cotreatment with growth hormone and gonadotropin for ovulation induction in
      hypogonadotropic patients: a prospective, randomized, placebo-controlled, dose
      response study. European and Australian Multicenter Study.
AB  - OBJECTIVE: To explore the dose-response relationship of cotreatment with GH in
      the augmentation of the ovarian response to stimulation by gonadotropins. DESIGN:
      Patients were randomly allocated to receive hMG and GH (4, 12, 24 IU) or hMG and
      placebo on alternate days for up to seven injections. PATIENTS: Sixty-four women
      with hypogonadotropic hypogonadism in eight centers in Europe and one in
      Australia. MAIN OUTCOME MEASURES: Gonadotropin dosage as a function of GH dose.
      RESULTS: The mean total number of ampules of hMG (75 IU FSH/ampule) required was
      37.2, 30.0, 25.6, and 22.3, respectively. There was also a significant dose
      response relationship observed for the duration of gonadotropin therapy and final
      daily effective dose required. Serum insulin-like growth factor I concentrations
      increased as a function of GH dose. No significant difference in E2
      concentrations, number of large follicles, or cancellation rate was noted between
      the four groups. There were significantly more pregnancies in the placebo groups
      compared with the GH groups. Nine adverse reactions were noted, one in the
      placebo and eight in the GH groups (1 in the 4-IU group, 5 in the 12-IU group,
      and 2 in the 24-IU group). CONCLUSIONS: We conclude that addition of GH to
      gonadotropin treatment exhibits a dose-related amplification of gonadotropin
      action on the ovary and reduction of gonadotropin dosage required to achieve
      ovulation induction. The study did not however define the minimum effective dose
      of GH for gonadotropin-stimulated ovulation induction.

PMID- 7589635
TI  - Correlation between the American Fertility Society classifications of adnexal
      adhesions and distal tubal occlusion, salpingoscopy, and reproductive outcome in
      tubal surgery.
AB  - OBJECTIVE: To compare the prognostic value of salpingoscopy with a current
      classification system of adnexal adhesions and distal tubal occlusion in patients
      with tubal infertility undergoing reconstructive tubal surgery. DESIGN:
      Prospective clinical study. SETTING: Department of Obstetrics and Gynecology of
      the Catholic University, a tertiary care University Center in Rome, Italy.
      PATIENTS: Fifty-five infertile patients with either adnexal adhesions (29
      patients) or hydrosalpinx (26 patients) undergoing reconstructive tubal surgery.
      INTERVENTIONS: Salpingoscopy performed concomitantly to salpingo-ovariolysis or
      salpingoneostomy at the time of either operative laparoscopy or laparotomy using
      microsurgical techniques. MAIN OUTCOME MEASURES: Salpingoscopic findings were
      compared with a current classification system of adnexal adhesions and distal
      tubal occlusion. The patients were followed for a mean follow-up of 49 months;
      the pregnancy rates achieved were correlated with the salpingoscopic findings and
      the classification system used. RESULTS: There was a significant correlation
      between the salpingoscopic grade and the occurrence of a term pregnancy for both
      the salpingo-ovariolysis and salpingoneostomy groups of patients. There was no
      significant correlation between the classification system used and the occurrence
      of a term pregnancy for both groups of patients. CONCLUSION: Salpingoscopy plays
      an important role in selecting the patients who may benefit the most from
      reconstructive tubal surgery.

PMID- 7589636
TI  - Effect of laparoscopic ovarian electrocautery on ovarian response and outcome of
      treatment with gonadotropins in clomiphene citrate-resistant patients with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the effect of ovarian electrocautery on the ovarian
      response to gonadotropic stimulation and pregnancy rate (PR) in clomiphene
      citrate (CC)-resistant women with polycystic ovary syndrome (PCOS) and high basal
      serum LH levels. DESIGN: Retrospective study. SETTING: Outpatient infertility
      clinic in a tertiary referral center. SUBJECTS: Twenty-two women with PCOS, high
      basal serum LH concentrations, and CC resistance who underwent laparoscopic
      ovarian electrocautery. Treatment with gonadotropin was scheduled after failure
      to ovulate spontaneously or conceive after electrocautery. Data from gonadotropin
      stimulated cycles were compared with data from treatment cycles in the same
      patients before ovarian electrocautery. MAIN OUTCOME MEASURES: Number of ampules,
      duration of induction phase, daily effective dose, PR, and pregnancy outcome.
      RESULTS: Markedly reduced basal serum LH concentrations and normal menstrual
      cyclicity in 41% of patients were recorded after laparoscopic ovarian
      electrocautery. Comparison of gonadotropin-stimulated cycles before and after
      electrocautery revealed significantly higher rates of ovulation and pregnancy
      after electrocautery as well as significant reduction in the number of ampules,
      daily effective dose, and duration of the induction phase with hMG and in daily
      effective dose with FSH. CONCLUSIONS: Our results indicate an increased ovarian
      sensitivity to gonadotropins after laparoscopic ovarian electrocautery. A
      preference for laparoscopic ovarian electrocautery over medical treatment in all
      or selected groups of CC-resistant PCOS patients is suggested.

PMID- 7589637
TI  - Clomiphene citrate and neural tube defects: a pooled analysis of controlled
      epidemiologic studies and recommendations for future studies.
AB  - OBJECTIVE: To estimate the degree to which neural tube defects (NTDs) are
      associated with periconceptional clomiphene citrate (CC) exposure in controlled
      epidemiologic studies, to investigate the consistency of study findings with
      respect to this association, and to identify key problems that future studies
      should address. DESIGN: Pooled analysis of 10 epidemiologic studies. SETTINGS:
      Hospitals and clinics. PATIENTS: Women undergoing treatment for infertility.
      INTERVENTIONS: Oral administration of CC. MAIN OUTCOME MEASURE: Prevalence ratio
      for NTDs. RESULTS: Ten controlled epidemiologic studies were identified that
      supplied sufficient data on CC and NTDs for inclusion. The estimated ratio of NTD
      prevalence among CC-exposed versus unexposed pregnancies ranged from 0.55 to 5.73
      among the studies, but the variation was compatible with random fluctuation. The
      estimated summary prevalence ratio was 1.08, with 95% confidence limits of 0.76
      and 1.51. CONCLUSION: This analysis indicates that an elevation in NTD risk due
      to CC cannot be ruled out, but any such elevation seems likely to be less than
      twofold, and there may be no elevation at all. Future studies should be designed
      to avoid several methodological problems not addressed in studies to date.

PMID- 7589638
TI  - Reproductive potential after an ectopic pregnancy.
AB  - OBJECTIVE: To measure statistically how soon pregnancy can occur after an ectopic
      pregnancy (EP) so as to determine the cumulative pregnancy rate and the risk
      factors involved in nonpregnancy. DESIGN: The risk of not getting pregnant after
      an EP (survivorship) was estimated for 120 patients followed up for up to 60
      months using the actuarial life-table technique. The risk factors involved in
      nonpregnancy, abortions, or live births were analyzed, using Cox regression
      models. SETTING: King Khalid University Hospital, Riyadh, Saudi Arabia. RESULTS:
      There were 68 pregnancies over the study period, with a conception rate of 56.7%.
      Using the actuarial life table, the cumulative probability of not achieving
      pregnancy in a patient decreased sharply during the first 12 months, followed by
      a gradual decrease up to 48 months. The Cox regression analysis showed a
      correlation between pregnancy and two variables, namely, age and history of prior
      EP. The chances of a pregnancy resulting in abortion or live birth also
      correlated with the presence of prior infertility, pelvic inflammatory disease
      (PID), or postoperative complications. CONCLUSION: Age and prior EP are important
      determinants in pregnancy rates after an EP. Similarly, history of PID,
      infertility, and postoperative complications are important risk factors in
      whether the pregnancy goes to term or ends in abortion.

PMID- 7589639
TI  - Antibodies to oxidized low-density lipoprotein and to cardiolipin in nonpregnant
      and pregnant women with habitual abortion.
AB  - OBJECTIVE: To determine the occurrence of antibodies to oxidized low-density
      lipoprotein (LDL) in women with a history of habitual abortion before and during
      pregnancy. DESIGN: Immunoglobulin G class antibodies to malondialdehyde modified
      LDL were determined by a solid-phase ELISA in 42 habitual aborters before
      pregnancy, in 39 patients during pregnancy, and in 23 comparable nonpregnant and
      22 pregnant control women without a history of abortion. In addition, we assessed
      the presence of anticardiolipin antibodies by ELISA in the same sera. SETTING:
      Departments I and II of Obstetrics and Gynecology, University Central Hospital of
      Helsinki, Helsinki, Finland. RESULTS: Early pregnancy was accompanied by a
      decrease in the median levels of antibodies to oxidized LDL both in habitual
      aborters and in the control series. Only one patient exhibited a raised level of
      antibodies to oxidized LDL before pregnancy but, during pregnancy, nine patients
      (23%) had elevated levels of antibodies to oxidized LDL, similar to women with a
      favorable outcome of pregnancy (6/27, 22%) and in women whose current pregnancy
      also ended in abortion (3/12, 25%). Cardiolipin binding antibodies were detected
      in three habitual aborters before pregnancy (7%) and in nine women during
      pregnancy (23%), with a tendency to be more frequent in patients with miscarrying
      pregnancies than in those with continuing pregnancies (4/12, 33% and 5/27, 19%).
      Antibodies to oxidized LDL and cardiolipin were simultaneously present in three
      habitual aborters with continuing pregnancies. CONCLUSIONS: Increased levels of
      antibodies to oxidized LDL and cardiolipin may be associated with habitual
      abortion.

PMID- 7589640
TI  - Naltrexone treatment restores menstrual cycles in patients with weight loss
      related amenorrhea.
AB  - OBJECTIVE: To evaluate whether the efficacy of naltrexone administration in
      patients with hypothalamic amenorrhea correlates to the response to an acute
      naloxone test. DESIGN: Thirty patients with hypothalamic amenorrhea associated
      with weight loss were studied. After naloxone test (4 mg in bolus IV) patients
      were divided into two groups: group A, nonresponsive (n = 15) and group B,
      responsive (n = 15). Group A underwent two cycles of hormonal replacement therapy
      with E2 patches and medroxyprogesterone acetate. Then all patients were
      administered naltrexone at the dosage 50 mg/d orally for 6 months. A third group
      of 10 amenorrheic patients were treated with oral placebo with the same schedule.
      RESULTS: Plasma gonadal steroid levels increased in all patients and in 24 of 30
      patients the menstrual bleeding occurred within 90 days from the beginning of
      treatment. After 6 months from naltrexone discontinuation, 18 of 24 patients
      still showed the occurrence of menstrual cycles. Luteinizing hormone plasma
      levels and LH pulse amplitude increased after 3 months of treatment and remained
      unchanged 6 months after naltrexone suspension. Plasma FSH levels did not show
      any change in any patient. The body mass index increased after 3 months in all
      patients who menstruated. Patients treated with placebo did not show any
      significant change in gonadotropins and gonadal steroid plasma levels.
      CONCLUSIONS: The present study supports the efficacy of naltrexone therapy for
      patients with hypothalamic amenorrhea either responsive or nonresponsive to
      naloxone test.

PMID- 7589641
TI  - Cardiovascular risk factors and combined estrogen-progestin replacement therapy:
      a placebo-controlled study with nomegestrol acetate and estradiol.
AB  - OBJECTIVE: To assess the effects of oral E2 replacement therapy combined with
      nomegestrol acetate, a 19-norprogesterone derivative, on cardiovascular risk
      factors. DESIGN: A double-blind randomized prospective study comparing the effect
      of a placebo and two oral E2-nomegestrol acetate combinations (1 mg-2.5 mg and
      1.5 mg-3.75 mg) over a three-cycle trial. SETTING: Department of Internal
      Medicine and Nutrition, Hotel-Dieu, Paris, France. PATIENTS: Fifty-seven
      nonhysterectomized women with natural menopause. MAIN OUTCOME MEASURES: Blood
      pressure, renin substrate, glucose, total cholesterol, high-density and low
      density lipoprotein cholesterol, triglycerides, apoproteins A1 and B,
      lipoprotein(a), antithrombin III, fibrinogen, plasminogen, prothrombin fragment 1
      + 2, protein C, and total and free protein S. RESULTS: Both treatments
      significantly reduced menopausal complaints, total cholesterol, low-density
      lipoprotein cholesterol and lipoprotein(a). Treatment with the 1.5 mg-3.75 mg
      combination resulted in a significant increase in apolipoprotein A1. No
      significant change were observed in other parameters. CONCLUSIONS: Sequentially
      combined with oral E2 in hormone replacement therapy, nomegestrol acetate had
      favorable effects on plasma lipids and lipoproteins. This nonandrogenic progestin
      decreased lipoprotein(a) levels as observed previously with medroxyprogesterone
      acetate combined with conjugated equine estrogens.

PMID- 7589642
TI  - Effects of hormone replacement therapy on weight, body composition, fat
      distribution, and food intake in early postmenopausal women: a prospective study.
AB  - OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) on body
      weight and composition, fat distribution, and food intake in women entering the
      climacteric. DESIGN: Prospective clinical study. SETTING: Outpatient menopause
      clinic at a tertiary medical center. PARTICIPANTS: Sixty-three early
      postmenopausal women (44 to 54 years old) were prospectively studied for 1 year.
      They consisted of two groups: group A, 34 subjects who initiated continuous
      estrogen and progestin treatment (daily oral conjugated estrogen 0.625 mg and
      medroxyprogesterone acetate 2.5 mg), and group B, 29 women who refused hormonal
      therapy and served as controls. The age, menopausal status, initial
      anthropometric measurements (weight, body mass index [BMI], fat mass, and waist
      to-hip girth ratio), and daily food intake (total caloric intake and food
      composition) were similar in both groups. INTERVENTIONS: Anthropometric
      measurements were performed before commencement of HRT use and after 12 months.
      MAIN OUTCOME MEASURES: Anthropometric measurements included BMI, waist-to-hip
      girth ratio, and body composition (the percentage of body fat and water)
      estimated by means of infrared interactance. Daily food intake was also recorded.
      RESULTS: The body weight and fat mass increased significantly in both the
      treatment (73.22 +/- 2.01 [mean +/- SE] to 75.57 +/- 1.12 kg) and the control
      group (71.45 +/- 3.11 to 73.51 +/- 1.23 kg). However, a significant shift from
      gynoid to android fat distribution was observed only in the control group (waist
      to-hip ratio shifted from 0.80 +/- 0.01 to 0.85 +/- 0.01), whereas no significant
      change was observed in the treatment group (0.81 +/- 0.01 to 0.82 +/- 0.01).
      Caloric and macronutrient intake did not change in either group. CONCLUSIONS:
      These results indicate that continuous daily estrogen and progestin replacement
      therapy neither prevents nor increases early postmenopausal weight gain and fat
      accumulation. However, it does minimize the shift from gynoid to android fat
      distribution.

PMID- 7589643
TI  - The effect of naloxone and metoclopramide on the secretion of luteinizing hormone
      in a hyperprolactinemic hypogonadotropic postmenopausal woman.
AB  - OBJECTIVE: To determine the role of opioidergic and dopaminergic activity in the
      suppression of GnRH0LH in a hyperprolactinemic state. DESIGN: Case report.
      SETTING: University hospital. PATIENT: A 68-year-old woman with a
      macroprolactinoma. INTERVENTIONS: Serial 10-hour IV infusions of naloxone and
      metoclopramide. MAIN OUTCOME MEASURE: Serum LH concentration. RESULTS: Naloxone
      induced a small but significant rise of serum LH levels, which displayed a
      pulsatile pattern. By contrast, metoclopramide elicited no significant response
      in LH secretion. CONCLUSION: Opioidergic but not dopaminergic neurotransmission
      plays a direct role in the suppression of LH secondary to hyperprolactinemia.

PMID- 7589644
TI  - The myometrium of postmenopausal women produces prolactin in response to human
      chorionic gonadotropin and alpha-subunit in vitro.
AB  - OBJECTIVES: To examine the effect of equimolar concentrations of hCG and
      dissociated alpha-subunit on PRL production by leiomyoma and myometrial tissue
      obtained from different hormonal states and to examine changes in PRL messenger
      RNA levels as PRL protein levels increased. DESIGN: Explant cultures of
      leiomyomas and myometrium were established and cultured for 96 hours. Tissue was
      studied from normal cycling women, postmenopausal women, pregnant women, and
      women undergoing GnRH agonist (GnRH-a) therapy. Cultured medium was collected at
      24, 48, and 96 hours and assayed for PRL. In selected experiments, tissue was
      processed at 0 and 96 hours to analyze messenger RNA (mRNA) levels. RESULTS:
      Human chorionic gonadotropin and alpha-subunit stimulated PRL secretion in [1]
      explant cultures of leiomyoma and myometrium from premenopausal women, [2]
      cultures of tissue treated in vivo with leuprolide acetate for both leiomyoma and
      myometrium, and [3] myometrium obtained from postmenopausal women. Postmenopausal
      myometrium was significantly more responsive to stimulation. Prolactin mRNA
      levels were documented to increase after hormone treatment in postmenopausal
      myometrium. CONCLUSION: Myometrium from postmenopausal women is very responsive
      to hCG and alpha-subunit. There is a difference in response between tissue
      obtained from menopausal women and that from women undergoing GnRH-a therapy to
      achieve a "medical menopause" and reproductive age women. The level of endogenous
      gonadotropins as well as the steroid milieu may modulate myometrial PRL
      secretion.

PMID- 7589645
TI  - Intracytoplasmic sperm injection: achievement of high pregnancy rates in couples
      with severe male factor infertility is dependent primarily upon female and not
      male factors.
AB  - OBJECTIVE: To determine the efficacy and factors affecting outcome of
      intracytoplasmic sperm injection (ICSI) in patients with severe male factor
      infertility. DESIGN: Prospectively designed clinical trial of patients selected
      to participate in the study based upon the following inclusion criteria: previous
      total failed fertilization or unsuitable sperm parameters for conventional IVF.
      SETTING: Tertiary care academic center. PATIENTS: Ninety-two consecutive couples
      undergoing IVF therapy augmented with ICSI during April through December 1994
      were studied. MAIN OUTCOME MEASURES: Fertilization and ongoing implantation and
      pregnancy rates (PRs). RESULTS: A total of 1,163 preovulatory oocytes were
      manipulated, yielding a diploid fertilization rate of 60.9%; the oocyte damage
      rate was 13.2%. The transfer rate was 95% with 43.1% of cycles having excess
      embryos that were cryopreserved. Overall, the clinical and ongoing PRs per
      transfer were 31.9% and 26.8%, respectively. None of the sperm parameters of the
      original semen analysis correlated with ICSI outcome. Female age did not affect
      fertilization results but had a significant impact on PR (< 34 years: 48.9%; 35
      to 39 years: 22.9%; > or = 40 years: 5.9% clinical PR per transfer). CONCLUSIONS:
      Intracytoplasmic sperm injection offers a new and powerful therapeutic option to
      treat couples with severe male factor infertility associated with a variety of
      sperm abnormalities. An adequate female age is a pivotal factor determining a
      successful outcome.

PMID- 7589646
TI  - The effect of sperm parameters on the outcome of intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To investigate the influence of sperm parameters on the fertilization
      and pregnancy rates in intracytoplasmic sperm injection (ICSI). DESIGN: A
      retrospective analysis of 130 cycles of ICSI performed for the treatment of male
      factor infertility. SETTING: The Egyptian IVF-ET Center. PARTICIPANTS: One
      hundred thirty couples with the diagnosis of male factor infertility or with
      previous failed fertilization in conventional IVF or subzonal sperm injection.
      INTERVENTION: Ovum pick-up and ICSI. MAIN OUTCOME MEASURE: Fertilization and
      pregnancy rates in relation to different semen parameters. RESULTS: A total of
      1,433 oocytes were retrieved and 1,071 metaphase II oocytes were injected. Normal
      fertilization occurred in 620 oocytes (58%). Embryo transfer was done for 128
      (98.5%) patients, and a total of 46 (35%) clinical pregnancies were achieved.
      There was no statistically significant difference in the fertilization or
      pregnancy rates between patients who had previously failed fertilization in
      conventional IVF, patients with subfertile semen, patients with semen between 1
      and 10 x 10(6)/mL, and patients with semen < 1 x 10(6)/mL. There was also no
      significant difference in the fertilization and pregnancy rates between patients
      with < 95% or > 95% teratozoospermia. CONCLUSION: In ICSI, the fertilization and
      pregnancy rates are not affected by different semen parameters as long as
      morphologically well-shaped live sperms could be used for the injection.

PMID- 7589647
TI  - Successful pregnancy outcome after cryopreservation of all fresh embryos with
      subsequent transfer into an unstimulated cycle.
AB  - OBJECTIVE: To assess the pregnancy outcome of freezing and storing all fresh
      embryos produced in a stimulated IVF cycle and replacing them in a subsequent
      nongonadotropin-stimulated cycle. DESIGN: Retrospective study. SETTING:
      University-associated assisted reproductive technology program. PATIENTS: We
      studied 36 patients (age range 23 to 44 years) who underwent cryopreservation of
      all fresh embryos in a controlled ovarian hyperstimulation (COH) cycle because of
      either the risk of severe ovarian hyperstimulation (24 patients, group 1) or the
      presence of an endometrial lining < 8 mm in thickness (12 patients, group 2).
      Five hundred fifty-five embryos were generated for replacement in 63 cycles. All
      embryos were cryopreserved in 1.5 M propanediol at the pronuclear or two-cell
      stage, and 264 embryos subsequently were transferred into a hormone replacement
      cycle (70%) or natural ovulatory cycle (30%). The average number of embryos
      transferred per patient was 4.2. RESULTS: Twenty-one clinical pregnancies were
      achieved, giving a pregnancy rate (PR) of 58.3% per patient (33.3% per cycle).
      The live birth rate was 50% per patient (28.6% per cycle). The implantation rate
      was 9.1%. Groups 1 and 2 had a similar PR per patient (58.3%). With 208
      cryopreserved embryos remaining and considering the 33.3% PR per cycle, we expect
      the overall extrapolated PR to be 63.9%. CONCLUSIONS: This is the first series
      showing that freezing and storing all fresh embryos produced in a stimulated IVF
      cycle and replacing them in a subsequent nongonadotropin-stimulated cycle results
      in successful PRs. These results underlie the importance of a successful
      cryopreservation program in IVF and could be a possible approach to overcoming
      the alleged adverse effects of COH on the endometrium, thereby improving the
      chances of pregnancy when numerous embryos are obtained simultaneously.

PMID- 7589649
TI  - Outcome of ovum donation in Turner's syndrome patients.
AB  - OBJECTIVE: To determine whether there is a difference in the pregnancy rate in
      women with Turner's syndrome (45,X) in an ovum donation program compared with
      women with other causes of premature ovarian failure. DESIGN: Retrospective chart
      review of women with Turner's syndrome (n = 11) and premature ovarian failure (n
      = 38) in a donor ovum program using variable dose and duration of E2 replacement
      therapy for endometrial preparation and using only transvaginal ultrasonographic
      assessment of endometrial response before ET. RESULTS: The pregnancy rates in
      Turner's syndrome patients and control subjects were 27% and 25%, respectively.
      Pregnancy rates were higher in the first cycle than in subsequent cycles for both
      groups (40% versus 8%). CONCLUSIONS: Turner's syndrome patients given a variable
      dose of estrogen, for endometrial preparation, with response assessed exclusively
      by transvaginal ultrasonography demonstrated pregnancy rates equal to patients
      with other causes of premature ovarian failure.

PMID- 7589648
TI  - Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation
      response and pregnancy outcome in patients undergoing in vitro fertilization.
AB  - OBJECTIVE: To test the hypothesis that elevated E2 levels on day 3 of IVF cycles
      without GnRH agonist (GnRH-a) are associated with reduced oocyte numbers and
      pregnancy rates (PRs). DESIGN: Day 3 levels of E2 and FSH were obtained from
      patients undergoing controlled ovarian hyperstimulation without GnRH analogue for
      IVF. PATIENTS: Five hundred ninety-two consecutive IVF cycles. RESULTS: Patients
      were grouped according to their day 3 E2 levels (< 30, 31 to 45, 46 to 60, 61 to
      75, and > 75 pg/mL [conversion factor to SI unit, 3.671]). The ongoing PR per
      retrieval for patients with E2 levels < 30 pg/mL was significantly higher than
      for patients with E2 levels 31 to 75 pg/mL. There were no pregnancies if the E2
      level was > 75 pg/mL. The mean number of oocytes per retrieval was significantly
      lower in patients from the E2 groups with E2 > 60 pg/mL compared with patients in
      groups with E2 < 60 pg/mL. Day 3 FSH and E2 levels also were evaluated
      simultaneously. In patients with the lowest levels of FSH and E2, the PR was the
      highest. No pregnancies occurred if the FSH level was > 17 mIU/mL (conversion
      factor to SI unit, 1.00) and the E2 level was > 45 pg/mL on day 3. CONCLUSIONS:
      For patients undergoing IVF without GnRH analogue, oocyte numbers and PRs
      decrease with increasing levels of day 3 E2. Combining day 3 FSH and E2 improved
      the prognostic ability of either of these hormones used alone.

PMID- 7589650
TI  - Recombinant human leukemia inhibitory factor does not enhance in vitro human
      blastocyst formation.
AB  - OBJECTIVE: To assess the effect of human recombinant leukemia inhibitory factor
      in different doses on human blastocyst formation. SETTING: A university-based
      tertiary referral center (The Toronto Hospital). INTERVENTIONS: Nontransferable
      human embryos (n = 473) at the two- to six-cell stage were obtained from patients
      undergoing IVF and were split randomly into five groups. Embryos in group A (n =
      164) were cultured as the control group in Ham's F-10 (GIBCO-BRL, Grand Island,
      NY) + 10% human sera. Embryos in groups B, C, D, and E (n = 54, 78, 87, and 80,
      respectively) were cultured in the same medium supplemented with human
      recombinant leukemia inhibitory factor in four different concentrations (5, 7.5,
      10, and 20 ng/mL, respectively). Morphological assessment of embryo development
      was recorded daily. MAIN OUTCOME MEASURE: Human blastocyst formation. RESULTS: No
      significant difference was detected in the rate of blastocyst formation of
      embryos in the study groups when compared with embryos in group A. CONCLUSIONS:
      This study shows that 5 to 20 ng/mL of recombinant leukemia inhibitory factor in
      standard medium does not enhance in vitro human blastocyst formation. It is
      possible that recombinant leukemia inhibitory factor may play a role at later
      stages of human embryogenesis and during implantation.

PMID- 7589651
TI  - In vitro fertilization versus tubal surgery: is pelvic reconstructive surgery
      obsolete?
AB  - OBJECTIVE: To compare the results of pelvic reconstructive surgery with
      cumulative success rates of IVF for couples with tubal factor infertility. DATA
      RESOURCES: Outcomes of pelvic surgery were obtained from a review of articles
      from the literature identified by directed Medline searches. Cumulative pregnancy
      rates of 771 couples with tubal factor infertility treated at the Cornell IVF
      program between December 1989 and December 1992 were calculated by life-table
      analysis. RESULTS: Overall delivery rate per transfer for patients with tubal
      factor was 28.9% (303 deliveries per 1,048 transfers) and did not appear to be
      affected significantly by the presence of a secondary diagnosis. A significant
      decline in pregnancy rates was observed with advancing age: age < 30 years,
      48.4%; 30 to 34 years, 44%; 35 to 38 years, 28%; 39 to 40 years, 20%; 41 to 42
      years, 9%; and > 42 years, 4.3%. Cumulative pregnancy rates for cycles 1 to 4
      were 32%, 59%, 70%, and 77%, respectively, in patients with only tubal factor,
      and 28%, 55%, 62%, and 75% in patients with tubal combined with other associated
      infertility factors. CONCLUSIONS: Our experience suggest that > 70% of women with
      tubal factor infertility will have a live birth within four cycles of treatment
      with IVF. These results compare favorably with the best outcomes after tubal
      reconstructive surgery. In older women, because of the rapid decline of fertility
      potential with advancing age, efforts should be directed toward the treatment
      method that provides the highest likelihood of success within the shortest time
      interval.

PMID- 7589652
TI  - No news here.

PMID- 7589653
TI  - Threshold intrauterine perfusion pressures for intraperitoneal spill during
      hydrotubation and correlation with tubal adhesive disease.
AB  - OBJECTIVE: To determine the minimum intrauterine perfusion pressure that will
      produce spill from the fallopian tubes into the peritoneal cavity and to
      correlate this pressure with the extent of tubal adhesive disease. DESIGN:
      Hydrotubation was performed at laparoscopy and intrauterine perfusion pressure
      was measured. The extent of peritubal and fimbrial adhesions was graded at
      laparoscopy. SETTING: Ambulatory surgery suites. PATIENTS: Ten patients with
      infertility and/or pelvic pain were enrolled in the study. Data from nine
      patients were analyzed. INTERVENTIONS: Measurement of intrauterine perfusion
      pressures. MAIN OUTCOME MEASURES: The minimum pressure that produced spill of dye
      from each fallopian tube and the correlation between extent of external tubal
      pathology and this threshold pressure. RESULTS: The median threshold pressure at
      which dye spilled from at least one fallopian tube was 100 mm Hg, and no spill
      occurred at pressures < 70 mm Hg. The threshold pressure was correlated
      negatively with the extent of tubal disease. CONCLUSIONS: Fluid with the same
      viscosity as hydrotubation dye will not spill into the peritoneal cavity through
      normal fallopian tubes until the intrauterine perfusion pressure exceeds 70 mm
      Hg. The threshold pressure is higher when tubal adhesive disease that can be
      visualized by laparoscopy is present.

PMID- 7589654
TI  - Elevated tubal perfusion pressures during selective salpingography are highly
      suggestive of tubal endometriosis.
AB  - OBJECTIVE: To investigate the possible etiologies of elevated tubal perfusion
      pressures. DESIGN: Analysis of 48 consecutive female patients with infertility
      who underwent laparoscopy and a gynecoradiological investigation as part of their
      infertility work-up. SETTING: Academically affiliated infertility center.
      INTERVENTIONS: A gynecoradiological investigation was performed using a
      previously reported standardized contrast injection system. Laparoscopy was
      performed routinely. RESULTS: Patients who demonstrated by laparoscopy to have
      endometriosis showed a significantly increased incidence of tubal blockage during
      initial hysterosalpingography (HSG) (12/26, 46.1%) compared with controls (2/14,
      14.3%). Patients with endometriosis also demonstrated significantly more
      frequently elevated tubal perfusion pressures (22/26; 84.6%) than women without
      disease (2/14, 14.3%) and significantly higher mean tubal perfusion pressures
      than women with normal pelvises (576 +/- 264 versus 450 +/- 268 mm Hg).
      CONCLUSION: Tubal blockage during initial HSG and elevated tubal perfusion
      pressures during selective salpingography are highly suggestive of tubal
      endometriosis. These data are the first evidence that tubal involvement with
      endometriosis may be more frequent than previously suspected. They also suggest
      that the performance of a gynecoradiological investigation, inclusive of
      selective salpingography, can greatly contribute to a presumptive diagnosis of
      endometriosis.

PMID- 7589655
TI  - Short-term endocrine response to gonadotropin-releasing hormone agonist initiated
      in the early follicular, midluteal, or late luteal phase in normally cycling
      women.
AB  - OBJECTIVE: To determine short-term pituitary and ovarian hormonal responses to
      GnRH agonist (GnRH-a) administered during various phases of the menstrual cycle,
      in the absence of controlled ovarian hyperstimulation (COH), to determine its
      independent effect on hormonal parameters previously demonstrated to influence
      assisted reproductive technology cycle outcome. DESIGN: Prospective, randomized,
      controlled crossover study of five regularly cycling women. The GnRH-a,
      leuprolide acetate (LA), was administered 1 mg SC daily for 5 days beginning on
      cycle day 3 (early follicular); 8 days post-LH surge (midluteal); or 13 days post
      LH surge (late-luteal). SETTING: Clinical research unit at a tertiary care
      medical center. MAIN OUTCOME MEASURES: Serum gonadotropins (LH and FSH) and
      gonadal steroids (E2, estrone [E1], P, A, and T) measured daily during GnRH-a
      administration begun in the early follicular, midluteal, or late luteal phase of
      the menstrual cycle. Gonadotropin pulse amplitude and frequency were determined
      after frequent serum sampling on the 2nd day of GnRH-a administration in each
      treatment cycle. RESULTS: Serum LH elevations, 4- to 10-fold greater than
      observed for FSH, did not differ by cycle day of GnRH-a initiation. Initial
      increases in FSH did not differ by cycle day, however, early follicular
      initiation resulted in a more pronounced suppression of FSH. Mean LH pulse
      amplitude and frequency increased to a similar extent in all three groups,
      however, FSH pulse amplitude and frequency varied significantly by cycle day of
      GnRH-a initiation. Gonadotropin-releasing hormone agonist initiated in the early
      follicular phase resulted in significant increases in E2, E1, and P levels
      compared with both midluteal or late luteal. Increases in serum androgens were
      significantly greater after early follicular and late luteal initiation as
      compared with midluteal GnRH-a initiation. CONCLUSIONS: Relative FSH suppression
      and marked androgen elevations in both late luteal and early follicular groups,
      which may have potential detrimental effects on oocytes of the developing cohort,
      suggest little advantage of late luteal or early follicular over midluteal
      initiation of GnRH-a for COH.

PMID- 7589656
TI  - Initial estradiol response predicts outcome of exogenous gonadotropins using a
      step-down dose regimen for induction of ovulation in polycystic ovary syndrome.
AB  - OBJECTIVE: To study ovarian stimulation and response patterns during a
      gonadotropin step-down dose regimen for induction of ovulation by applying a
      decremental dose regimen in polycystic ovary syndrome (PCOS) patients. DESIGN:
      The present prospective study involves 28 infertile clomiphene citrate-resistant
      PCOS patients during gonadotropin-induced cycles using a modified step-down dose
      regimen (and adjuvant GnRH agonist medication). Applied gonadotropin doses
      included initial daily doses of 150 IU IM followed by two reducing steps (37.5 IU
      each) based on sonographic criteria to a final daily dose of 75 IU IM. SETTING:
      Anovulatory infertile women in an academic referral center. INTERVENTION: Daily
      blood withdrawal and transvaginal pelvic ultrasound. MAIN OUTCOME MEASURES: Serum
      FSH and E2 concentration and follicle growth were investigated daily during
      gonadotropin administration. RESULTS: An initial 2.1-fold increase in serum FSH
      levels was observed followed by a subsequent decrease of 10% (median) per day for
      4 days. Growth of ovarian follicles was sustained and ovulation achieved
      (midluteal P, 11.7 +/- 1.3 ng/mL; conversion factor to SI unit, 3.180; mean +/-
      SD) in 22 patients. Major variability in day 3 E2 increase (range, 67 to 866
      pg/mL; conversion factor to SI unit, 3.671)--not related to differences in FSH
      serum concentrations and without changes in follicle number and size--suggests
      differences in ovarian sensitivity for FSH stimulation. A strong correlation (r =
      0.82) was found between day 3 E2 increase and the chance of ovulation. Moreover,
      E2 levels on the day of gonadotropin dose reduction predict (r = 0.68) chances of
      late follicular phase E2 levels exceeding 871 pg/mL (conversion factor to SI
      value, 3.671). CONCLUSIONS: These findings provide the endocrine basis for the
      concept of gonadotropin induction of ovulation using a step-down dose regimen.
      Initial E2 increase (before initiation of follicle growth) represent differences
      in ovarian sensitivity to gonadotropins and predict treatment outcome.

PMID- 7589658
TI  - Evidence that an altered prolactin release is consequent to abnormal ovarian
      activity in polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate whether endogenous dopaminergic activity is impaired in
      polycystic ovary syndrome (PCOS)-affected women and is normalized by medical
      ovariectomy. PATIENTS: Women with PCOS untreated (n = 23) and treated for 3
      months with GnRH analogue (GnRH-a) administration (n = 10) and normal cycling
      young women (n = 23) as controls. INTERVENTIONS: Acute blockade of dopaminergic
      receptors by the IV administration of 5 mg of the dopaminergic receptor blocking
      agent sulpiride (sulpiride test) was performed 3 to 7 days after the initiation
      of spontaneous menses in cycling women or medroxyprogesterone acetate-induced
      menses in PCOS women. In PCOS women treated with GnRH-a administration (goserelin
      depot, 3.6 mg SC every 28 days), the sulpiride test was repeated 10 to 15 days
      after the third GnRH-a administration. MAIN OUTCOME MEASURE: Basal PRL levels and
      PRL increase induced by sulpiride. RESULTS: Basal PRL levels and the PRL response
      to sulpiride were increased in women with PCOS. In women with PCOS medical
      ovariectomy induced by GnRH-a administration reversed to normal both basal and
      sulpiride-stimulated PRL levels. CONCLUSIONS: In women with PCOS the abnormal
      regulation of PRL and presumably of hypothalamic neurotransmitters controlling
      PRL secretion is not a primary alteration but it is likely dependent on abnormal
      ovarian functionality.

PMID- 7589659
TI  - Prorenin is elevated in polycystic ovary syndrome and may reflect
      hyperandrogenism.
AB  - OBJECTIVE: To examine the null hypothesis that women with polycystic ovary
      syndrome (PCOS) produce similar levels of prorenin and other components of the
      ovarian-derived prorenin to angiotensin cascade (ODPAC) at baseline and after
      stimulation with clomiphene citrate (CC) or hMG when compared with normal age-
      and weight-matched ovulatory controls. DESIGN: Prospective controlled clinical
      trial. SETTING: Infertility clinic in a university-based county hospital and a
      hospital-based private infertility practice. PATIENTS: Twenty-eight infertile
      women aged 18 to 35 years. Thirteen patients were diagnosed with PCOS. Fifteen
      normal ovulatory patients who were matched for age and weight served as controls.
      INTERVENTIONS: Twenty patients were stimulated with CC and eight were stimulated
      with hMG. MAIN OUTCOME MEASURES: Serum E2, P, T, androstenedione (A), DHEAS, LH,
      FSH, and plasma prorenin, active renin, and angiotensin II (Ang II) were measured
      at baseline and during the preovulatory and midluteal phases of the stimulation
      cycles. RESULTS: Baseline plasma prorenin in PCOS was higher than that of
      follicular phase controls. Plasma prorenin correlated significantly with
      peripheral androgen levels. Prorenin, active renin, and Ang II increased in
      response to gonadotropins with the largest increases occurring in control
      patients receiving CC. An association was seen between ovulation with CC and
      lower baseline levels of active renin. CONCLUSIONS: The null hypothesis was
      rejected. Infertile women with PCOS have higher baseline prorenin levels when
      compared with age- and weight-matched ovulatory controls. There is a significant
      correlation between prorenin and the peripheral levels of androgens produced
      during ovarian stimulation. Baseline active renin levels may be predictive of
      ovulation with CC.

PMID- 7589657
TI  - Ovulation induction with gonadotropins as sole treatment in infertile couples
      with open tubes: a randomized prospective comparison between intrauterine
      insemination and timed vaginal intercourse.
AB  - OBJECTIVE: To assess if ovulation induction with gonadotropins alone is an
      appropriate treatment in couples affected by unexplained and mild male factor
      related infertility and if the concomitant IUI improves the pregnancy rate (PR).
      DESIGN: Prospective and randomized trial. SETTING: Infertility Centre of
      Department of Obstetrics and Gynecology of the University of Cagliari, Cagliari,
      Italy. PATIENTS: Two hundred couples affected by unexplained or mild male factor
      related infertility were assigned randomly to one of two treatment groups: group
      A (n = 100), treated with three consecutive cycles of ovulation induction with
      gonadotropins associated with timed vaginal intercourse; group B (n = 100),
      treated with three consecutive cycles of ovulation induction with gonadotropins
      associated with IUI. MAIN OUTCOME MEASURE: Pregnancy rate. RESULTS: The PRs
      obtained with ovulation induction with gonadotropins associated with IUI were
      similar to those obtained with ovulation induction with gonadotropins associated
      with timed vaginal intercourse. CONCLUSION: Ovulation induction with
      gonadotropins alone may be as effective as ovulation induction with gonadotropins
      associated with IUI in couples with unexplained and mild male factor infertility
      and can represent the initial treatment option for its minimal invasivity and
      reduced cost and organizational problems.

PMID- 7589660
TI  - Exaggerated effects of progestogen on uterine artery pulsatility index in
      Turner's syndrome patients receiving hormone replacement therapy.
AB  - OBJECTIVE: To investigate the effect of estrogen and progestogen on the
      resistance to blood flow in the uterine arteries of Turner's syndrome patients.
      DESIGN: Prospective clinical study. SETTING: A tertiary infertility clinic.
      PATIENTS: Five Turner's syndrome patients, six patients who had surgical
      castration, and five patients with idiopathic primary ovarian failure.
      INTERVENTIONS: The patients were treated with 2 mg E2 valerate to which 500
      micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal
      color Doppler was used to measure pulsatility index in the uterine arteries at
      eight regular intervals during a single cycle. MAIN OUTCOME MEASURE: Pulsatility
      index of the uterine arteries. RESULTS: The administration of norgesterel to
      Turner's syndrome patients resulted in an increase in pulsatility index that was
      significantly higher than in patients who had surgical castration (confidence
      interval = 0.17 to 2.42). CONCLUSION: The uterine arteries of Turner's syndrome
      patients are more sensitive to the tonic effect of progestogen. If manifest in
      cardiac arteries also this phenomenon may be partly responsible for the increased
      incidence of cardiovascular disease and shorter life expectancy in Turner's
      syndrome patients. To achieve optimal protection from cardiovascular disease,
      Turner's syndrome patients may benefit from hormone replacement treatment
      containing altered doses of estrogen and progestogen.

PMID- 7589662
TI  - Growth hormone, insulin-like growth factor-I axis, and insulin secretion in
      hyperandrogenic adolescents.
AB  - OBJECTIVE: To assess GH and insulin-like growth factor I (IGF-I) axis variability
      in hyperandrogenic adolescents with different sources of androgen excess and
      their relationship with insulin resistance. DESIGN: Baseline IGF-I, insulin-like
      growth factor binding protein-1 (IGFBP-1), IGFBP-3, GH response to the exercise
      propranolol test, and insulin responses to a standard oral glucose tolerance test
      were compared among patients with functional ovarian hyperandrogenism,
      hyperandrogenic nonfunctional ovarian hyperandrogenism patients, and age-matched
      controls. SETTING: Outpatient clinic in a medical center. PATIENTS: Twenty-one
      adolescents with ovarian (group A) and 17 with nonovarian (group B)
      hyperandrogenism, and 20 controls. RESULTS: Serum IGF-I and poststimulated GH
      levels were similar among groups, whereas serum IGFBP-3 levels were significantly
      lower in group A than in controls. Mean serum insulin levels were significantly
      higher in patients than in controls, whereas 24% of patients had abnormal insulin
      responses to glucose and/or insulin sensitivity indexes. Serum IGFBP-3 levels
      correlated negatively with the free androgen index (free androgen index = T/sex
      hormone-binding globulin [SHBG] x 100), whereas mean serum insulin levels
      correlated positively with the free androgen index and negatively with SHBG
      levels in all subjects. CONCLUSIONS: Hyperinsulinemia is common in
      hyperandrogenic adolescents and correlates with the degree of hyperandrogenism
      and not with the androgen source. Hyperinsulinemia and decreased IGFBP-3 levels
      may enhance IGF-I bioavailability, which in turn may both decrease SHBG levels
      and increase androgen production.

PMID- 7589661
TI  - Further evidence of reproductive immaturity among gynecologically young pregnant
      adolescents.
AB  - OBJECTIVE: To obtain further information about the reproductive maturity of
      adolescents who become pregnant soon after menarche. We hypothesized that the
      length of the follicular phase of the menstrual cycle antedating conception is
      related inversely to the gynecological age of the adolescent mother at
      conception. DESIGN: Observational clinical study. SETTING: Pregnant volunteers in
      a multidisciplinary adolescent-oriented maternity program. PATIENTS: Pregnant
      adolescents with accurate pregnancy dating. MAIN OUTCOME MEASURE: We studied the
      difference between the estimated date of confinement (EDC) computed from the
      stated last menstrual period (EDCLMP) and the EDC computed from ultrasound
      studies (EDCUS) in a group of 66, 12 to 19 year olds. A prolonged follicular
      phase was defined as EDCUS-EDCLMP > 0 and shortened follicular phase was defined
      as EDCUS-EDCLMP < or = 0. RESULTS: Pearson correlations revealed a statistically
      significant inverse relationship between gynecological age and the duration of
      the follicular phase antedating conception when the follicular phase was
      prolonged. Within this subgroup of patients EDCUS exceeded EDCLMP by 15.6 +/- 7.3
      days when conception occurred within 3 years of menarche and 6.2 +/- 6.0 days
      when conception occurred > or = 3 years after menarche. CONCLUSIONS: Our findings
      support the hypothesis that some adolescents conceive before establishing a fully
      mature adult ovulatory pattern.

PMID- 7589663
TI  - Application of Chinese hamster ovary cells transfected with the recombinant human
      follicle-stimulating hormone (FSH) receptor for measurement of serum FSH.
AB  - OBJECTIVES: To evaluate the activity of the serum FSH bioactivity in patients
      with premature ovarian failure (POF). DESIGN: Prospective study. SETTING:
      Infertility and gynecology outpatient clinics at the Gunma University School of
      Medicine, Gunma, Japan. PATIENTS: Twelve women, aged 27 to 39 years, with POF and
      nine postmenopausal women. INTERVENTIONS: Serum samples obtained from
      postmenopausal women and POF patients. The immunoglobulin (Ig)G fractions of some
      sera from POF patients were prepared by 20% polyethylene glycol. MAIN OUTCOME
      MEASURES: Serum samples were measured simultaneously by the bioassay system and
      immunoradiometric assay (IRMA). RESULTS: The bioassay values correlated with
      those obtained by IRMA, and the correlation coefficient and the slope of the
      regression lines calculated from nine pairs of assay values from the
      postmenopausal women were 0.867 and 1.10, respectively. The mean of the
      biologic:immunologic ratios of sera from postmenopausal women and POF patients
      were 1.44 and 1.25, respectively. CONCLUSIONS: The IgG fractions of some sera
      from POF patients showed stimulatory or inhibitory effect on cyclic adenosine
      3':5' monophosphate production compared with that from postmenopausal women.
      These results may reflect the more complex pathophysiological states of the
      patients with POF.

PMID- 7589664
TI  - Cocultured blastocyst cryopreservation: experience of more than 500 transfer
      cycles.
AB  - OBJECTIVE: To present our experience using cocultured cryopreserved and
      transferred blastocysts. DESIGN: Retrospective study of patients undergoing
      transfer of cryopreserved blastocysts. SETTING: Three different IVF centers.
      PATIENTS: Four hundred sixty-seven thawed cycles from January 1991 to June 1994.
      MAIN OUTCOME MEASURE: Pregnancy rate per cycle after transfer of pre-embryos
      developed from thawed blastocysts. RESULTS: One thousand two hundred thirty-nine
      blastocysts were thawed. Of these, 1,033 (83%) survived thawing and were
      transferred. Five hundred sixty-three thawed cycles resulted in 516 (92%)
      receiving intrauterine transfer. One hundred twelve clinical pregnancies were
      established, resulting in a 21.7% pregnancy per transfer with a 19% ongoing rate.
      The implantation rate of 13.4% results from 138 implanted pre-embryos. There was
      a higher PR in the programmed cycle (79/302; 26.2%) compared with the natural
      cycle (6/47;13%). CONCLUSIONS: Freezing at the blastocyst stage is a proven and
      reliable method in IVF technology. Although there may be fewer pre-embryos, their
      ability to implant appears to approach the potential of a fresh transfer.

PMID- 7589665
TI  - Prospective, auto-controlled study on reinsemination of failed-fertilized oocytes
      by intracytoplasmic sperm injection.
AB  - OBJECTIVE: To evaluate the possible influence of late fertilization after
      standard IVF on the results of reinsemination of assumed failed-fertilized
      oocytes by microinjection and to examine the correlation between the effect of
      aging of (failed-fertilized) oocytes and the ability of these oocytes to become
      fertilized. DESIGN: Trial 1: Group 1 (injected-day 1), 93 failed-fertilized
      oocytes injected 1 day after ovum pick-up; group 2 (control), 82 failed
      fertilized oocytes with no microinjection performed. Trial 2: Group 1 (ICSI-day
      1), 40 failed-fertilized oocytes injected 1 day after ovum pick-up; group-2 (ICSI
      day 2), 40 failed-fertilized oocytes injected 2 days after ovum pick-up. In
      addition, 35 two- to eight-cell stage embryos, obtained after ICSI of IVF failed
      fertilized oocytes, were fixed for cytogenetic analysis. MAIN OUTCOME MEASURES:
      Normal and abnormal fertilization and embryo development. RESULTS: Trial 1: 53%
      normal (2 pronuclear [PN]) and 25% abnormal (> or = 3PN) fertilization rates were
      obtained in group 1 (injected-day 1), and 71% of the 2PN and 74% of the > or =
      3PN oocytes cleaved with < 50% fragmentation. No pronuclear (> or = 2PN)
      development occurred in the control group. Trial 2: 45% and 8% normal and 25% and
      40% abnormal fertilization rates were obtained, respectively, after ICSI of 1-day
      old and 2-day-old failed-fertilized oocytes. Two days after microinjection, 67%
      and 67% of the 2PN and 80% and 44% of the > or = 3PN oocytes cleaved with < 50%
      fragmentation in group ICSI-day 1 and in group ICSI-day 2, respectively.
      CONCLUSIONS: Late fertilization after initial in vitro insemination does not play
      a role in the high fertilization rate obtained after reinsemination of assumed
      failed-fertilized oocytes by ICSI. Normal (2PN) fertilization rate, however,
      decreases strongly and the abnormal (> or = 3PN) fertilization rate increases
      with oocyte aging and derived embryos seem to have a high incidence of
      cytogenetic abnormalities.

PMID- 7589667
TI  - The achievement of pregnancies using assisted reproductive technologies for male
      factor infertility after retroperitoneal lymph node dissection for testicular
      carcinoma.
AB  - OBJECTIVE: To evaluate the success of electroejaculation with assisted
      reproductive technologies (ART) in anejaculate men after retroperitoneal lymph
      node dissection (RPLND) for testicular cancer. DESIGN: Retrospective clinical
      study. SETTING: Tertiary care, university-affiliated IVF program. PATIENTS:
      Anejaculate men after RPLND, spouses. INTERVENTIONS: Electroejaculation,
      microsurgical sperm aspiration, various assisted reproductive technologies. MAIN
      OUTCOME MEASURES: Sperm density and motility, fertilization rate, pregnancy rate
      (PR). RESULTS: Compared with patients not receiving chemotherapy, patients who
      received chemotherapy had diminished average sperm densities and motilities (63 x
      10(6) and 20% versus 101 x 10(6) 32%, respectively); decreased fertilization
      rates per cycle for IVF and intracytoplasmic sperm injection (ICSI) (11% versus
      26%, respectively); lower PRs per cycle of hMG-IUI and IVF (14% versus 60% and 8%
      versus 50%, respectively). No pregnancies were achieved with natural cycle-IUI,
      clomiphene citrate-IUI, or GIFT. Two couples progressed to intracytoplasmic sperm
      injection with one achieving the successful delivery of healthy twins. The
      overall PR per cycle was 22%. CONCLUSIONS: Patients receiving chemotherapy had
      decreased sperm densities, motilities, fertilization, and PRs for each modality
      used. Rectal probe electroejaculation with ART can help anejaculate men after
      RPLND achieve biologic paternity. An early move to the more aggressive therapies
      (hMG-IUI, IVF, ICSI) is supported.

PMID- 7589666
TI  - Prognostic value of day 3 estradiol on in vitro fertilization outcome.
AB  - OBJECTIVE: To evaluate the prognostic value of day 3 E2 levels, independent of
      day 3 FSH levels, on responses to ovulation induction and subsequent pregnancy
      rates (PRs) in IVF-ET patients. DESIGN: Prospective, observational. SETTING:
      University-based tertiary care and private reproductive endocrine-infertility
      units. PATIENTS AND INTERVENTIONS: A total of 225 patients underwent 292 IVF
      cycles with luteal phase GnRH agonist suppression and hMG stimulation. MAIN
      OUTCOME MEASURES: We evaluated response and outcome data including age, day 3 FSH
      and E2 levels from a menstrual cycle before IVF, ampules of hMG used, maximum E2
      level, cancellation rates, and clinical PR. RESULTS: Despite similar age, number
      of ampules of hMG, and peak E2 levels, patients with an elevated E2 level (E2 >
      or = 80 pg/mL) (conversion factor to SI unit, 3.671) on day 3 of a cycle before
      IVF-ET achieved a lower PR per initiated cycle (14.8% versus 37.0%) and had a
      higher cancellation rate (18.5% versus 0.4%) compared with those with E2 levels <
      80 pg/mL. Even when patients with elevated FSH levels (FSH > or = 15 mIU/mL)
      (conversion factor to SI unit, 1.00) were excluded (leaving 279 cycles), those
      with an elevated day 3 E2 still had a lower PR per initiated cycle (14.8% versus
      38.9%) and maintained a higher cancellation rate (18.5% versus 0.4%). When the
      day 3 E2 was > or = 100 pg/mL there was a 33.3% cancellation rate and no
      pregnancies were achieved. CONCLUSION: Patients who presented with an elevated
      day 3 E2 (> or = 80 pg/mL) in a cycle before IVF-ET had a higher cancellation
      rate and achieved a lower PR independent of FSH level. A day 3 E2 level, in
      addition to a day 3 FSH level, appears very helpful in prospectively counseling
      patients regarding cancellation risk and ultimate IVF-ET success.

PMID- 7589670
TI  - Serum is more effective than albumin in promoting human embryo development and
      implantation.
AB  - OBJECTIVE: To compare the effects of serum with those of Albuminar-5 (Armour
      Pharmaceutical Co., Eastbourne, Sussex, United Kingdom) as medium supplements to
      Earl's balanced salt solution (EBSS) for IVF and subsequent embryo development.
      DESIGN: A retrospective study. Gametes and embryos from 318 patients were
      cultured in the presence of serum (group 1). Gametes and embryos from 130
      patients were cultured in the presence of Albuminar-5 (group 2). Embryos obtained
      from IVF were replaced into the uterus within 48 hours after insemination.
      Surplus bipronucleate embryos were cultured up to 14 days with either serum or
      Albuminar-5. SETTING: Two tertiary referral fertility clinics; university
      teaching hospital. PATIENTS: Four hundred forty-eight patients with a wide
      spectrum of causes of subfertility, ranging in age from 24 to 43 years. MAIN
      OUTCOME MEASURES: Fertilization rate, pregnancy rate (PR), implantation rate, and
      surplus embryo development in vitro. RESULTS: The PR for group 1 patients was
      higher than that of group 2 (27.0% versus 15.4%, respectively). Although
      fertilization rates were identical in the two groups, cumulative embryo scores
      and implantation rates were significantly higher in group 1. There was no
      difference between the groups in age distribution, types of ovarian stimulation,
      numbers of patients with day 1 or day 2 transfers, or luteal phase support. Of 31
      embryos cultured with serum, 54.8% reached the fully expanded blastocyst stage
      and 25.8% hatched. Of 19 embryos cultured with Albuminar-5, only 5.3% reached the
      fully expanded blastocyst stage and none hatched. CONCLUSIONS: The results
      suggest that, under certain conditions, serum supplementation yields better
      results than protein supplementation alone. The latter may be suitable only in
      conjunction with additional components.

PMID- 7589671
TI  - Ovarian volume: a novel outcome predictor for assisted reproduction.
AB  - OBJECTIVE: To determine the potential of ovarian volume as a predictor of
      assisted reproduction outcomes. DESIGN: Retrospective chart review. SETTING:
      University-based assisted reproduction program. PATIENTS: One hundred eighty
      eight women initiating their first cycle of assisted reproduction. INTERVENTIONS:
      None. MAIN OUTCOME MEASURES: Pretreatment transvaginal ultrasound ovarian
      measurements were compared with subsequent ovulation induction parameters (peak
      E2, numbers of oocytes, and embryos) and cycle outcome (cancellation and
      pregnancy). RESULT: Total ovarian volume and volume of the smallest ovary were
      significant variables predicting peak E2 and numbers of oocytes and embryos.
      Total ovarian volume was a predictor of cycle cancellation and volume of the
      smallest ovary a predictor of clinical pregnancy. Large ovarian volumes are
      associated with good assisted reproductive technology outcomes whereas small
      ovarian volumes are associated with poor outcomes. CONCLUSION: Beyond maternal
      age, total ovarian volume, and volume of the smallest ovary are significant
      predictors of the success of assisted reproductive techniques.

PMID- 7589668
TI  - Hyaluronidase activity in human semen: correlation with fertilization in vitro.
AB  - OBJECTIVES: To characterize the relationship between hyaluronidase activity and
      the currently used methods of assessing sperm function and to determine whether
      the measurement of hyaluronidase activity can provide a reliable index of sperm
      fertilizing capacity in man. DESIGN: Nonrandomized prospective study. SETTING:
      Tertiary referral IVF and andrology clinics affiliated with the University of
      Toronto. SUBJECTS: Four hundred eight samples were collected, 248 from men
      undergoing investigation in andrology and fertility clinics and 160 from men
      participating in an IVF program. INTERVENTIONS: Semen samples were treated with
      NP-40 in buffer to extract hyaluronidase and applied to a circular well cut into
      a petri dish containing a mixture of hyaluronic acid and agar. Enzyme activity
      was assessed by measuring the area of substrate hydrolysis. RESULTS: Significant
      positive correlations were found between hyaluronidase activity and sperm
      concentration, motility, and the percentage of sperm with normal morphology in
      the studied samples. In the IVF samples, hyaluronidase activity was found to be
      related significantly to the fertilization rate. Moreover, we were able to
      establish values of hyaluronidase below which no fertilization occurred and above
      which fertilization of at least one oocyte was achieved. CONCLUSION: These
      results suggest that measurement of hyaluronidase activity may provide a useful
      method for assessing the integrity of the acrosomal enzyme system, providing a
      simple and reliable predictor of the fertilizing potential of human sperm.

PMID- 7589669
TI  - A zona biochemical change and spontaneous cortical granule loss in eggs that fail
      to fertilize in in vitro fertilization.
AB  - OBJECTIVE: To determine the extent of biochemical changes in the zona pellucida
      (ZP) and cortical granule release in eggs failing to fertilize in IVF. DESIGN:
      After insemination, unactivated eggs without two pronuclei (PN) were studied by
      high resolution microscopy and fluorescent probes to determine cortical granule
      density and meiotic stage. After ZP isolation, proteins from individual ZPs were
      biotinylated, electrophoresed, and visualized by western blots with avidin
      chemiluminescence. Controls included mouse unfertilized and fertilized eggs and
      human germinal vesicle stage oocytes and > or = 3PN eggs. SETTING: University
      medical center and hospital tertiary care IVF-ET program. RESULTS: Many of the
      unfertilized eggs were in metaphase and had relatively low cortical granule
      densities indicative of cortical granule loss. Approximately one half of the ZPs
      showed evidence of biochemical hardening with a modification of a 90 to 100 x
      10(3) molecular (weight) ratio (M(r)) ZP protein. The 3PN eggs had few cortical
      granules and their ZPs had a pronounced 90 to 100 x 10(3) M(r) modification that
      was not detected in germinal vesicle stage ZP controls. CONCLUSION: The observed
      changes in ZP biochemistry and cortical granule quantitation demonstrate that
      failed fertilization is frequently associated with spontaneous cytoplasmic, but
      not nuclear, activation. In affected eggs, these changes could prevent
      fertilization in routine IVF and in cases of reinsemination. The relationship of
      changes in the ZP and cortical granules to infertility and in vitro culture
      requires further investigation. The 90 to 100 x 10(3) M(r) ZP protein
      modification can be detected biochemically with 1/10 of a human ZP.

PMID- 7589673
TI  - Sperm morphology and in vitro fertilization outcome: a direct comparison of World
      Health Organization and strict criteria methodologies.
AB  - OBJECTIVE: To perform a direct comparison of two sperm morphology methodologies
      with regard to IVF outcome. DESIGN: Blinded comparison of two methods of
      morphology assessment using the same morphology slides. PATIENTS: Data were
      obtained from 132 couples in a consecutive series of patients undergoing IVF.
      MAIN OUTCOME MEASURES: Two practical end points were selected for analysis for
      each couple: the presence of any fertilization and the number of fertilized eggs.
      Normal traditional morphology was defined as > or = 40% normal forms in a sample
      and normal strict criteria was defined as > or = 4%. RESULTS: Traditional
      morphology demonstrated a higher sensitivity and negative predictive value than
      strict criteria (87% versus 61%, and 68% versus 36%, respectively). Positive
      predictive value and specificity were also numerically greater but did not reach
      statistical significance. Abnormal traditional morphology, but not strict
      criteria, was associated with reduced fertilization even among samples with
      normal sperm concentration and motility. Samples with normal morphology were
      associated with a greater number of fertilized eggs per couple than those with
      abnormal morphology: this difference was 3.2 fertilized eggs for traditional
      morphology and 1.6 for strict criteria. Overall, for samples with < 40% by
      traditional morphology only one case yielded more than two fertilized eggs. In
      contrast, up to five fertilized eggs were noted for the lowest strict criteria
      scores. CONCLUSIONS: Comparison of traditional morphology and strict criteria
      with regard to IVF outcome favored traditional morphology in several areas. In
      particular, low scores were more predictive of poor IVF outcome.

PMID- 7589672
TI  - Platelet-activating factor-acetylhydrolase activity in follicular fluid of
      patients undergoing in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To examine the role of platelet-activating factor (PAF) metabolism in
      the periovulatory processes. DESIGN: The PAF-acetylhydrolase activity in the
      follicular fluid (FF) obtained in conjunction with IVF-ET procedure was assayed
      and its activity was related to oocyte maturation. The PAF-acetylhydrolase
      activity also was related to the concentration of various ovarian hormones.
      SETTING: All patients were managed and treated at Oita Medical University
      Hospital, Oita, Japan. PATIENTS: The study concerned 30 women between 28 and 36
      years of age with tubal infertility. MAIN OUTCOME MEASURE: The activity of PAF
      acetylhydrolase in FF was assayed as well as E2 and P. Oocyte maturation also was
      evaluated. RESULTS: Platelet-activating factor-acetylhydrolase activity was
      decreased significantly in the FFs of patients with a successful outcome of their
      pregnancies compared with the nonsuccessful group. Estradiol levels were
      negatively correlated with PAF-acetylhydrolase activities in the FFs. No
      correlation was found between the PAF-acetylhydrolase activity and P
      concentration in the FF. Significantly more mature and less immature oocytes were
      recovered in the group who subsequently became pregnant compared with the
      nonpregnant group. CONCLUSIONS: It is suggested that the decrease in PAF
      acetylhydrolase activity may result in an increase of PAF in the FFs, which in
      turn may contribute to a successful pregnancy. The determination of PAF
      acetylhydrolase activity in FF may serve as a prognostic marker for the
      evaluation of oocytes that are utilized in IVF-ET procedure.

PMID- 7589674
TI  - Progesterone induces human sperm chemotaxis.
AB  - OBJECTIVE: To characterize the molecular nature of the chemotactic signal for
      sperm contained in human follicular fluid (FF). DESIGN: Follicular fluid was
      fractionated and several procedures were followed to the physicochemical initial
      characterization of sperm chemotactic compound(s). MAIN OUTCOME MEASURE: Relative
      chemotactic activity of each fraction was measured in a double chamber device.
      RESULTS: Sperm chemotaxis was found to be associated with a lipid-like molecule
      extracted from FF. Several steroids were assayed individually and only P showed
      sperm chemotactic properties in dose-response curves. CONCLUSIONS: In this paper
      we present experimental evidence to support the hypothesis that P, the main
      steroid component of FF, is a mediator of sperm chemoattraction in human beings.

PMID- 7589675
TI  - Prospective study of hormonal and semen profiles in marathon runners.
AB  - OBJECTIVE: To investigate the effect of marathon training on hormonal and semen
      profiles in male athletes. DESIGN: Prospective longitudinal study over 1 year.
      SETTING: Department of Obstetrics and Gynaecology, University of Cape Town, South
      Africa. PARTICIPANTS: Twenty-four healthy male marathon runners, 25 to 54 years
      of age. MAIN OUTCOME MEASURES: Hormonal evaluation included determination of
      plasma concentrations of total T, LH, FSH, PRL, E2, and P. Semen analyses
      included an evaluation of count, motility, morphology, and volume. These profiles
      were correlated with training intensity. RESULTS: The intensity of training
      increased significantly in the first 5 months of the study. This was accompanied
      by a significant rise in serum PRL levels and a fall in P levels. No other
      significant hormonal changes were identified. The semen volume and sperm motility
      and morphology fell significantly during training, but there was no significant
      alteration in the sperm count. CONCLUSION: This longitudinal study demonstrates
      that endurance training can modify significantly hormonal profiles and semen
      parameters in long-distance runners.

PMID- 7589676
TI  - The clinical characteristics of 82 patients with Sertoli cell-only testis
      histology.
AB  - OBJECTIVE: To determine the clinical and laboratory features associated with
      Sertoli cell-only testis histology. DESIGN: Case-controlled retrospective
      analysis. SETTING: University-based male infertility clinic. PATIENTS: Eighty-two
      patients with germ cell aplasia histology on testis biopsy from 1984 to 1994.
      Hormonal findings from a control group of 34 fertile men with normal semen
      analyses were used for comparison. MAIN OUTCOME MEASURES: History, physical
      examination, semen analysis, and endocrine findings. RESULTS: Sertoli cell-only
      histology was observed in 82 of 652 (13%) biopsies performed in infertile men
      with azoospermia. A major medical illness or genital anomaly (hypospadias,
      cryptorchidism) was found in 31 men (38%). On physical examination, 75% of
      patients had small testis (< 18 mL volume) and 45% had abnormally soft testis. On
      hormone evaluation only serum FSH concentration was elevated significantly (33
      mIU/mL [33 IU/L]) compared with fertile controls (7.1 mIU/L [7.1 IU/L]). Patients
      (6%) with confirmed elevations in serum PRL had lower FSH values than those men
      with normal PRL levels. Normal ejaculate volumes were observed in all patients.
      CONCLUSIONS: In approximately 38% of patients, germ cell aplasia is associated
      with underlying disease states; in the remainder it is largely idiopathic. The
      physical examination is often characteristic, along with an elevated serum FSH
      concentration. Normal FSH levels tend to be associated with hyperprolactinemia in
      these men.

PMID- 7589677
TI  - Multifetal reduction of high-order multiple pregnancy: comparison of obstetrical
      outcome with nonreduced twin gestations.
AB  - OBJECTIVE: To compare the obstetric outcomes of twin pregnancies obtained as a
      result of multifetal pregnancy reduction to those in which pregnancy reduction
      had not been used. DESIGN: Retrospective analysis. SETTING: University-based
      tertiary care infertility clinic. PATIENTS: Seventy-four twin pregnancies
      continuing beyond 10 weeks. Of these, 32 gestations had undergone reduction to
      twins at 10 weeks. MAIN OUTCOME MEASURES: Gestational age at delivery, birth
      weights, pregnancy complications. RESULTS: All pregnancies advanced beyond 20
      weeks gestation. The mean gestational age at delivery of the reduction group was
      33.8 versus 35.7 weeks in the nonreduced group; only 25% of reduced pregnancies
      reached 37 weeks compared with 57.9% of nonreduced twins. The mean fetal birth
      weights of the two groups differed significantly (reduced: 2,038 g, nonreduced:
      2512 g). The gestational age at delivery in patients reduced from triplets was
      significantly greater than in pregnancies reduced from quadruplets or higher.
      Multiple regression analysis revealed that for a given gestational age at
      delivery, a history of pregnancy reduction was associated with decreased birth
      weight. CONCLUSION: These data suggest that multifetal pregnancy reduction does
      not reverse completely the decreased gestational age and impaired fetal growth
      associated with high-order multiple pregnancy. Furthermore, fetal growth of
      reduced pregnancies seems to be impaired independent of the gestational age at
      which delivery occurs.

PMID- 7589678
TI  - Flare-up of endometriosis induced by gonadotropin-releasing hormone agonist
      leading to bowel obstruction.
AB  - OBJECTIVE: To report a case of intestinal obstruction that developed shortly
      after preoperative administration of a GnRH analogue (GnRH-a) that caused flare
      up and rapid progression of enteric endometriosis. DESIGN: Case report. SETTING:
      University tertiary reproductive endocrinology practice. PATIENT: A 34-year-old
      nulligravid female with progressive severe symptomatic endometriosis.
      INTERVENTIONS: Planned preoperative administration of GnRH-a for 3 months
      followed by extirpative surgery and hormone replacement therapy. Instead, total
      abdominal hysterectomy, bilateral salpingoophorectomy, resection of the
      obstructed ileocecal junction, and side-to-side ileo-ascending enterocolostomy
      was performed. RESULTS: Preoperative GnRH-a administered in the midfollicular
      phase resulted in flare-up of preexisting ileocecal endometriosis that rapidly
      progressed, resulting in partial small bowel obstruction. CONCLUSION:
      Gonadotropin-releasing hormone agonist should be used with caution when there is
      known or suspected enteric endometriosis. Consideration should be given to
      blocking the agonistic effect of GnRH-a in this setting by the prior or
      concomitant use of progestins or danazol.

PMID- 7589679
TI  - Characteristics of blood hemostatic markers in a patient with ovarian
      hyperstimulation syndrome who actually developed thromboembolism.
AB  - OBJECTIVE: To investigate whether a patient with ovarian hyperstimulation
      syndrome (OHSS) demonstrated characteristic changes in the blood hemostatic
      markers before she developed thromboembolism. DESIGN: Patients with OHSS had
      blood drawn to determine hemostatic markers and related factors. PATIENTS: Twenty
      three OHSS patients, including a case complicated with thromboembolism. SETTING:
      The IVF-ET program of the Department of Obstetrics and Gynecology, The University
      of Akita, School of Medicine. MAIN OUTCOME MEASURES: Blood hemostatic markers and
      related factors. RESULTS: The patient with thromboembolism demonstrated marked
      leukocytosis and higher levels of activation in the blood markers related to
      fibrinolytic system, such as alpha 2 plasmin inhibitor, plasmin-alpha 2
      antiplasmin complexes, and D-dimers, before the onset of this episode.
      CONCLUSION: Marked leukocytosis and higher levels of activation of the
      fibrinolytic system may be the signs of imminent thromboembolism in OHSS
      patients.

PMID- 7589680
TI  - Manipulation of sperm before intracytoplasmic sperm injection improves
      fertilization rates.
AB  - OBJECTIVE: To determine the effect of sperm manipulation before intracytoplasmic
      sperm injection (ICSI) on fertilization rates. DESIGN: Three methods of sperm
      manipulation before direct ICSI were compared in two sibling oocyte trials.
      SETTING: In vitro fertilization unit within a teaching hospital. PATIENTS:
      Patients undergoing infertility treatment using ICSI. INTERVENTIONS: Oocytes were
      inseminated by ICSI. MAIN OUTCOME MEASURE: Fertilization rate. RESULTS: In the
      first trial, a standard manipulation technique gave a 67% fertilization rate
      compared with 64% with a minimal manipulation technique. In the second trial the
      standard technique gave a significantly greater fertilization rate compared with
      no prior manipulation (67% versus 45%). CONCLUSIONS: Manipulation of sperm before
      direct ICSI is not mandatory for fertilization but significantly improves the
      fertilization rate.

PMID- 7589681
TI  - Intracellular calcium measurements in individual human sperm demonstrate that the
      majority can respond to progesterone.
AB  - OBJECTIVE: To determine if human spermatozoa could be immobilized and
      intracellular calcium measurements made on individual cells to measure what
      proportion can respond to P. DESIGN: Spermatozoa were loaded with Fura 2 (Sigma
      Chemical Co., Poole, Dorest, United Kingdom) and suspended in 10% gelatin at 37
      degrees C. A thin layer of the suspension was cooled to room temperature (20
      degrees C to 25 degrees C) and [Ca2+]i was measured with a fluorescence
      microscope equipped with dual wavelength excitation and an image analysis system.
      SETTING: University-based laboratory. PARTICIPANTS: Semen was obtained from four
      fertile donors to a donor insemination program. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: [Ca2+]i was calculated from the ratio of Fura 2 fluorescence excited at
      340 nm and that excited at 366 nm. RESULTS: One hundred six of 114 sperm examined
      (93%) demonstrated a significant response to P but the size and duration of the
      response was variable. CONCLUSION: These data demonstrate that most sperm can
      respond to P.

PMID- 7589682
TI  - Effects of urine on the functional quality of human spermatozoa.
AB  - OBJECTIVE: To determine the effect of urine on sperm function and to elucidate
      the reason by which it may be deleterious. DESIGN: Prospective controlled in
      vitro study. INTERACTIONS: Sperm were exposed to various concentrations of pooled
      urine in Ham's F-10 Medium supplemented with 3.5 g% bovine serum albumin (GIBCO,
      Grand Island, NY) and sperm exposed to Ham's F-10 Medium with pH and osmolality
      adjusted to mimic that of the urine (pH 5.4; 520 mOsm). MAIN OUTCOME MEASURE:
      Sperm motility and the ability of sperm to penetrate and migrate into mucus and
      to penetrate hamster oocytes were determined. RESULTS: All sperm variables
      studied were significantly decreased when the sperm were exposed to > or = 40%
      urine. Potential of hydrogen- and osmolality-adjusted Ham's F-10 did not
      significantly affect the sperm function. CONCLUSION: Urine is deleterious to
      sperm function and may involve other biochemical factors that are unrelated to pH
      and osmolality of urine.

PMID- 7589684
TI  - New treatment of idiopathic severe oligozoospermia with mast cell blocker:
      results of a single-blind study.
AB  - OBJECTIVE: To determine whether mast cell blocker (tranilast) improves fertility
      and/or semen parameters in severe oligozoospermia. DESIGN: Placebo-controlled
      single-blind clinical study. SETTING: Nagoya University Hospital Andrology
      Clinic, Nagoya, Japan. PATIENTS: Fifty men with sperm density < 5 x 10(6)
      sperm/mL, normal serum gonadotropins, and T, and a fertile partner were enrolled
      in this study. INTERVENTIONS: Patients were prescribed randomly 300 mg/d
      tranilast or a placebo, three tablets per day, for 3 months. Semen and blood
      samples were collected before and after therapy. Semen parameters, serum
      gonadotropins, T, and PRL were evaluated before and after therapy. RESULTS: The
      pregnancy rate (PR) in the mast cell blocker group was 28.6% compared with 0% in
      the placebo group. There was a statistical difference in the PR between groups.
      The mast cell blocker group had significantly higher levels of sperm density,
      sperm motility, and total motile sperm count. There were no differences between
      the mast cell blocker and placebo groups in seminal volume and normal sperm
      morphology. CONCLUSIONS: The authors conclude that mast cell blocker is
      clinically useful for the treatment of idiopathic severe oligozoospermic men.

PMID- 7589683
TI  - Pregnancy in an azoospermic patient with markedly elevated serum follicle
      stimulating hormone levels.
AB  - OBJECTIVE: To assess the possibility of achieving a pregnancy in an azoospermic
      patient with markedly elevated serum FSH level. DESIGN: A case report. SETTING:
      In vitro fertilization program at the Instituto Valenciano de Infertilidad.
      PATIENT: An azoospermic patient with small testes and serum FSH level (38.7
      mIU/mL) higher than three times normal. Testicular biopsy revealed Sertoli cell
      only syndrome with focal spermatogenesis. INTERVENTIONS: Intracytoplasmic
      microinjection of testicular tissue-extracted spermatozoa. MAIN OUTCOME
      MEASUREMENTS: Fertilization rate, cleavage rate, clinical pregnancy. RESULTS:
      Eight of 11 (73%) intact oocytes showed two pronuclei. All of them cleaved
      normally. Four embryos were replaced into the uterine cavity and the other four
      were cryopreserved. A twin clinical pregnancy was achieved. CONCLUSION:
      Spermatozoa may be present in testicular biopsy specimens of azoospermic patients
      with severe spermatogenic failure despite markedly elevated serum FSH level.
      These patients can be fertile after intracytoplasmic testicular sperm
      microinjection.

PMID- 7589685
TI  - Diagnosis of vasal obstruction with seminal vesiculography: an alternative to
      vasography in select patients.
AB  - OBJECTIVES: To determine whether the pelvic and inguinal portion of the vas
      deferens can be visualized during seminal vesiculography. DESIGN: Retrospective
      review of the seminal vesiculograms performed in six patients to determine the
      frequency of visualization of the vas deferens. A prospective evaluation to
      determine the amount of contrast necessary to visualize the vas deferens was
      performed in three patients. RESULTS: The vas deferens was visualized down to the
      level of the scrotum in four of the six initial studies examined retrospectively.
      The vas deferens was visualized adequately after the infusion of > or = 10 mL of
      contrast in all three studies performed prospectively. CONCLUSION: Seminal
      vesiculography is a minimally invasive diagnostic alternative to vasography that
      can be used to document the patency of the pelvic and inguinal portions of the
      vas deferens in select patients.

PMID- 7589687
TI  - "A donor by any other name".

PMID- 7589686
TI  - Management of ascites and pleural effusions in ovarian hyperstimulation syndrome.

PMID- 7589688
TI  - Predictive value of gonadotropin-releasing hormone test in Kallman's syndrome?

PMID- 7589689
TI  - A nurse is a nurse is a nurse.

PMID- 7589690
TI  - Orlando creates health community initiative.

PMID- 7589691
TI  - Healthcare changes bring increased liability risk for nurses.

PMID- 7589692
TI  - Early intervention through mentoring in order to enhance minority participation
      in nursing.

PMID- 7589693
TI  - I-J revisited: is the I-J genetic restriction in downregulation due to an
      endogenous superantigen analogous to mammary tumour virus (Mtv)-encoded
      endogenous superantigen?
AB  - This article puts forward the hypothesis that the I-J genetic restriction
      observed between certain downregulatory (suppressor) T cells and antigen
      presenting cells is due to an endogenous superantigen analogous to the mouse
      mammary tumour virus (Mtv) products encoded by the open reading frames in the 3'
      long terminal repeat (LTR) of mtv's. In its weak form this hypothesis asserts
      that the I-J genetic restriction is due to an endogenous superantigen ligand on
      antigen presenting cells, which crosslinks the V beta and/or V alpha chains of
      certain T cell receptors (TCR) with major histocompatibility complex (MHC) class
      II, and that MHC together with this superantigen ligand causes positive selection
      of T cells bearing the appropriate I-J+ TCR in the thymus. In the periphery these
      T cells recognize peptide/MHC complex in the presence of the superantigen. In its
      strong form the hypothesis states that this superantigen ligand for TCR and MHC
      is encoded by integrated virus genome, e.g. Mtv. These possibilities can now be
      approached experimentally and their exploration may uncover one of the ways in
      which T cells are assigned to different functions, including downregulation.

PMID- 7589694
TI  - T-cell mediated immunosuppression and its implications for the development of
      protective immunity.
AB  - The mechanisms by which regulatory CD4- CD8+ suppressor T cells (Ts) and CD4+ CD8
      amplifier T cells (Ta) influence the magnitude of the antibody response to the
      capsular polysaccharide antigen of type III Streptococcus pneumoniae are reviewed
      in detail. This represents the best-characterized experimental model system
      available for demonstrating how subsets of T cells act in a negative and positive
      manner to control the magnitude of an antibody response. The fact that
      transferred Ts and Ta elicit their effects in athymic immunized mice affirms,
      that such regulatory T cells are antigen-specific and act on immune B cells to
      produce the effects observed. The ability of the lipid A and the inner core
      region oligosaccharide fractions of bacterial lipopolysaccharide to abolish and
      increase the expression of Ts function, respectively, is examined with respect to
      its immunomodulatory potential and its possible role in enhancing the virulence
      of Gram-negative bacteria.

PMID- 7589695
TI  - Immunoregulation mediated by T-cell clusters.

PMID- 7589697
TI  - On the role of interleukin-10 in the induction and maintenance of specific
      transplantation tolerance.
AB  - The role of a cytokine synthesis inhibitory factor, interleukin-10 (IL-10), in
      the induction and maintenance of neonatal transplantation tolerance was studied
      in mice. We showed that neonatal spleen cells (NSC) significantly inhibited
      interleukin-2 (IL-2) production by activated T cells from adult mice.
      Simultaneously we demonstrated a high expression of the IL-10 gene in stimulated
      spleen cells from newborn mice. However, neutralizing monoclonal antibody (mAb)
      anti-IL-10 did not abolish the NSC-mediated suppression of IL-2 production. IL
      10, therefore, does not appear to be the principal inhibitory molecule
      responsible for the suppression of IL-2 production. Similarly, specific
      alloantigen-activated spleen cells from adult tolerant animals were profoundly
      hyporeactive in IL-2 production. This hyporeactivity was not reversed to a
      positive reactivity in the presence of mAb anti-IL-10. In addition, anti-IL-10
      antibody enhanced proliferation in mixed lymphocyte cultures of cells from both
      control and tolerant animals, but the antibody did not abrogate specific
      hyporeactivity of cells from tolerant mice. These results thus showed that
      newborn animals were nonspecifically and tolerant animals specifically deficient
      in IL-2 production, but that IL-10 in neither case appeared to be responsible for
      this IL-2 hyporeactivity.

PMID- 7589696
TI  - Immunological tolerance to xenogeneic grafts induced by cyclophosphamide in adult
      animals.
AB  - Data on tolerance of mice to rat tissue grafts obtained during the last 20 years
      are presented in this article. The method of tolerance induction, which spared
      recipients' lymphoid tissue and which needed no supporting antigen or
      immunodepressant injection, is described. These tolerant mice had long-lasting
      (more than 6 months) xenograft survival, had no cytotoxic antibodies and delayed
      type hypersensitivity (DTH) reaction to donor antigens but showed only a partial
      decrease in the levels of mixed lymphocyte reaction (MLR) and non-cytotoxic
      antibody production. According to indirect evidence, tolerance arose as a result
      of clonal deletion and was maintained subsequently by antigen-specific T
      suppressor cells and Thy-negative lymphocytes.

PMID- 7589698
TI  - The Czech National Register of bone marrow donors.

PMID- 7589699
TI  - From clones of cells to clones of genes.
AB  - Three approaches to study the immune system are presented. First is the limiting
      dilution analysis, second is the analysis of the polypeptide patterns of
      lymphocytes by two-dimensional gel electrophoresis, and the third is the
      utilization of a partitioned cDNA library for establishing a gene catalog and
      proteinpaedia. All the approaches were used to study clonal diversity and clonal
      heterogeneity. The gene catalog which is already established is available to
      recover genes expressed in various lymphocyte clones.

PMID- 7589700
TI  - Analysis of the adoptive transfer of delayed hypersensitivity and T cell
      repertoire in severe combined immunodeficiency mice reconstituted with human
      lymphocytes.
AB  - The functional capacity of human T cells to passively transfer delayed
      hypersensitivity (DH) was analysed in severe combined immunodeficiency (SCID)
      mice. The tissue distribution of human peripheral blood lymphocytes (PBL) was
      analysed by 51chromium labelling 1 and 24 h after intravenous cell injection.
      Labelled PBL from purified protein derivative (PPD)-positive healthy individuals
      mainly localize in the spleen, liver and lungs, with no arrival in the peripheral
      lymphoid organs and at the site of antigen challenge (footpad). According to such
      defective distribution, human PPD-immune cells failed to passively transfer PPD
      specific DH to SCID recipients when cells were injected either intravenously or
      intraperitoneally (systemic transfer). On the contrary, PPD-immune cells were
      able to transfer DH to PPD when injected directly into the footpad (local
      transfer). Both memory (CD45RA-) and naive (CD45RA+) enriched subsets were
      equally able to transfer local DH. The long-term reconstitution of the human
      immune system in SCID mice was analysed after intraperitoneal PBL transfer (hu
      PBL-Scid) by phenotypic analysis, immunoglobulin level, and human DNA detection.
      Moreover, the reconstitution of the V beta T cell receptor (TCR) repertoire in
      SCID mice was analysed by anchored polymerase chain reaction (PCR) showing that
      all the 22 V beta families were expressed in the spleen of hu-PBL-SCID mice.
      Moreover, scanner analysis of Southern blotting revealed the selective expansion
      of distinct V beta families (V beta 3, V beta 6, V beta 8, V beta 13.1, V beta
      14, V beta 17), suggesting that human lymphocytes could recognize specific
      antigens or superantigens in the SCID environment.

PMID- 7589701
TI  - HLA-G mRNA forms in human trophoblasts and peripheral blood lymphocytes:
      potential use in prenatal diagnosis.
AB  - HLA-G limited polymorphic gene maps to the human major histocompatibility complex
      (MHC) class I subregion and encodes the molecule which is the only MHC class I
      antigen expressed on cytotrophoblast cells at the maternal-fetal interface. In
      this tissue, HLA-G primary mRNA is differentially spliced. We have used a
      sensitive hot start reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique to investigate the expression of HLA-G gene in first trimester
      trophoblasts and adult peripheral blood cells. PCR amplification with HLA-G
      primers specific of exon 3 has enabled us to demonstrate a novel alternatively
      spliced form of HLA-G mRNA present in fetal first trimester trophoblasts and
      lacking exon 4 (HLA-G4). Cloning the whole PCR product and hybridizing
      recombinant bacterial colonies with specific probes has permitted evaluation of
      HLA-G4 vs. full length mRNA frequency at approximately 1:200. Moreover, the
      presence of HLA-G transcripts was found at a very weak level in adult peripheral
      blood lymphocytes and equally in B- and T-cell populations. These results are
      relevant in the context of immune tolerance and in the potential use of HLA-G
      transcripts as a marker for RT-PCR detection of the fetal cells in maternal as a
      marker for RT-PCR detection of the fetal cells in maternal blood.

PMID- 7589702
TI  - Behavior in vitro of long-term cultured bone marrow or blood cells from chronic
      myeloid leukemia: adhesion molecules and differentiation antigens as detected by
      immunocytochemistry.
AB  - Long-term cultures (LTC) were established from chronic myeloid leukemic bone
      marrow or blood. As detected by immunocytochemistry using 25 different monoclonal
      antibodies, the in vitro cultured cells express a variety of adhesion molecules
      and differentiation antigens. beta 1 and beta 2 integrins are constantly present
      on long-term cultured cells. CD4, CD54, CD58, and CD71 markers become highly
      expressed on the cells after about 10 days in vitro while CD56 is permanently
      lacking. Only 5 of the 17 patients studied had between 25 and 85 per cent CD33
      and CD34 differentiation antigen-positive cells initially in the bone marrow or
      blood. There was a decrease to less than 10 per cent after six to eight weeks in
      culture. In later stages of long-term culture, monocytes/macrophages become the
      dominating cell types. Blast cells are admixed to these cells in varying numbers.
      In 4 of the 17 cases studied long-term cultures converted to cell lines showing
      indefinite cell growth. The cells were identified as B cell blasts spontaneously
      transformed by Epstein Barr virus (EBV). The permanent myeloid and monocytic
      leukemia cell lines K-562, HL-60, KG-1, RC-2a, CTV-1, THP-1, and U-937 were
      likewise tested for adhesion molecules and differentiation antigens. A stable
      marker expression was found, the pattern of which is characteristic of each cell
      line. CD4 is frequently present on myeloid and monocytic leukemia cell lines (HL
      60, RC-2a, THP-1, and U-937). Exceptionally, CD2 and CD34 were shown on KG-1.
      CD49e, CD49f, CD44, and CD71 are expressed on all cell lines tested.

PMID- 7589703
TI  - Myelopeptide-1 blocks the T-suppressor activity.
AB  - The immunoregulatory properties of two myelopeptides (MPs) [Phe-Leu-Gly-Phe-Pro
      Thr (MP-1) and Leu-Val-Val-Tyr-Pro-Trp (MP-2)] were studied. The antibody
      production-stimulating activity was determined in the culture of lymph node cells
      (LNC) obtained from mice on the 4th day of the secondary immune response to sheep
      red blood cells (SRBC). T suppressors were induced in mouse spleen cell (SC)
      culture by incubation with concanavalin A (Con A) for 48 h. Immune LNC were
      cultured alone or with T suppressors in the presence or absence of MPs. After
      cultivation, the immune response was estimated by enumeration of indirect
      antibody forming cells (AFC). MP-1, but not MP-2, increased the number of AFC and
      abolished Con A induction of T suppressors in SC suspensions. MP-1 also fully
      blocked and MP-2 only partly decreased the inhibitory effect of T suppressors in
      the culture of immune LNC. Immunoregulatory peptide MP-1 may participate in
      regulation of the antibody response and in development of some states of
      immunological tolerance.

PMID- 7589704
TI  - Immunohistochemical analysis of cells infiltrating Rous sarcoma virus-induced
      tumors in chickens.
AB  - The aim of our experiments was the analysis of peripheral blood lymphocytes (PBL)
      and tumor infiltrating lymphocytes (TIL) in chicken inbred congenic lines, CB
      line with regressing and CC line with progressing RSV-induced sarcomas. For
      serological analysis, monoclonal antibodies to CD4, CD8, TCR1, TCR2, MHC class I
      and class II antigens were used. Significant differences determined by flow
      cytometry in CD4+ and CD8+ populations of PBL between CB chickens with tumors in
      progressive phase and CC chickens were not confirmed by means of TIL analysis.
      TIL were analysed either in suspension prepared from tumors by means of flow
      cytometry or on cryostat section of tumors. But using the histochemical method we
      observed more non-specific esterase positive cells in cryostat sections from CB
      than CC tumors. The role of macrophages in the regression of RSV-induced tumors
      in CB chickens has to be further analysed.

PMID- 7589705
TI  - Immunoreactivity of ageing C57BL female mice rendered tolerant to the H-Y
      antigen.
AB  - Transplantation tolerance to the H-Y antigen, induced in neonatal or young adult
      C57BL female mice, beneficially affected their immunoreactivity during the
      process of ageing. The tolerance acquired in 2-month-old females significantly
      increased their splenocyte graft-versus-host (GVH) reactivity and the production
      of interleukin-2 (IL-2) at the age of 18 months. The neonatally induced tolerance
      also resulted in a higher weight of the thymus and a significantly enhanced GVH
      reactivity of thymocytes in 18-month-old females compared to control mice of the
      same age.

PMID- 7589706
TI  - Origin of the North American house mouse.
AB  - The house mouse, Mus domesticus, was introduced to the American continent in the
      post-Columbian era. We have used mouse chromosome 17 DNA probes to trace the
      origin of the wild house mice on the East Coast of the United States. Of the four
      probes used, one in particular proved to be informative in this regard. The
      D17Tu20 probe defines a polymorphism at a locus telomeric of the H-2 complex.
      TaqI restriction enzyme digests of genomic DNA blotted and hybridized with the
      D17Tu20 probe revealed the existence of restriction fragments shared by mice from
      the Atlantic coast of England, France, and the United States but absent in all
      other tested populations sampled from different parts of the world. This unique
      polymorphic pattern apparently arose by the loss of two restriction sites in the
      population on the coast of Brittany. The mutations then presumably spread to
      England, and from there to the United States. Since the mutations are also
      present in mice from Florida, English (rather than Spanish) mouse populations may
      have been either the sole or the main source of immigrants to the eastern United
      States. This conclusion is also supported by data obtained with the other probes.
      Presence of the D17Tu20 mutations in some of the laboratory strains indicates
      that American wild mice contributed to the gene pool of the inbred strains. We
      postulate that the colonization of North America by English wild mice began in
      the second half of the seventeenth century.

PMID- 7589708
TI  - Immunological tolerance: the key for an understanding of the immune reaction.

PMID- 7589707
TI  - Chicken T cell coreceptors.

PMID- 7589709
TI  - The major histocompatibility complex in man.

PMID- 7589710
TI  - The genetics of HLA.

PMID- 7589711
TI  - Presentation of antigen and MHC-restricted unresponsiveness.

PMID- 7589712
TI  - The regulation of expression of histocompatibility antigens on the cell surface;
      molecular genetic basis.
AB  - Histocompatibility antigens play a fundamental role in the immune functions by
      their polymorphic capture structure for binding exogenous and endogenous peptides
      and presenting them to the appropriate T and B cell receptors. The genetic
      background of the control of synthesis of the histocompatibility antigens is very
      complex including several loci controlling the wide polymorphic variation of
      class I and class II histocompatibility molecules and their regulation of
      expression. Most significant variability in the presence or absence of
      histocompatibility antigens could be observed during development,
      differentiation, and activation. The tissue-specific expression is influenced by
      pathological events such as malignant transformation, viral infection and genetic
      defectiveness as well. The research in the field of molecular genetics of the MHC
      in the last decade revealed, upstream of the coding genes of class I and class II
      molecules, a very complex regulatory machinery including a series of genes termed
      enhancer and promoter region. At the DNA level, various gene boxes and regulatory
      elements were discovered, which are activated by the binding of the appropriate
      histone proteins, cytokines or hormones responsible for the upregulation and
      downregulation of histocompatibility antigen expression. Regulation is mainly
      functioning at the transcriptional level, but other factors such as viral
      proteins, oncogenes, biomolecules, and physical effects take part, either
      indirectly or directly affecting the regulatory genes and DNA binding proteins.
      The increasing knowledge about the regulatory machinery may lead to the
      introduction of genetic manipulation, either experimental or clinical, with the
      aim of changing the expression of histocompatibility molecules on the cell
      surface in order to achieve normal or demanded immune functions.

PMID- 7589713
TI  - Biological meaning of the MHC.

PMID- 7589714
TI  - Vascular pattern in the chorioallantoic membrane (CAM) after laser/photosensitive
      compound treatment. II. Microscopic findings.
AB  - The formation of clusters of densely packed primitive erythrocytes in growing
      capillaries and primitive vascular stems of chicken chorioallantoic membrane
      (CAM) after laser/meso-tetra(sulfonatophenyl)porphine dodecahydrate tetra-sodium
      salt (TPPS4) was studied. The soluble TPPS4 penetrates easily through the CAM
      epithelium and stroma into vascular lumina and accumulates predominantly in red
      blood cells. Accumulation of TPPS4 in immature erythrocytes persisted in higher
      levels in comparison with the primitive endothelium after day 2 of incubation.
      Laser/TPPS4-treated primitive red blood cells became sticking on the inner
      surfaces of tiny CAM capillaries and numerous "erythrocytic plugs" were quickly
      formed in irradiated CAM areas. Small erythrocytic clusters were also found after
      prolonged laser irradiation especially in superficial capillary network in CAM.
      Slight red blood cell disintegration, followed by blood leakages through vascular
      ruptures, was found after day 2 of further reincubation.

PMID- 7589715
TI  - Overexpression of p53 and MDM2 proteins in cervical neoplasia.
AB  - Sixteen methacarn-fixed and paraffin-embedded cervical squamous lesions were
      examined using monoclonal antibodies to p53 and MDM2 in order to compare the
      expression of both proteins in cervical neoplasia. Standard avidin-biotin or
      streptavidin-biotin immunoperoxidase techniques were employed. The results show
      that the overexpression of both proteins takes place in a meaningful proportion
      of cervical neoplastic lesions. The expression of either protein is not very
      frequent in CIN 1 and 2. The overexpression of either p53 (9/12) or MDM2 (4/10)
      proteins was recorded in the group of more advanced lesions, their level
      fluctuating from 10% to 60% positive cells. The results suggest the possibility
      of an interaction of the p53 and MDM2 proteins in some cases of cervical
      neoplasia.

PMID- 7589716
TI  - Ion chromatographic determination of cyanide released from flaxseed under
      autohydrolysis conditions.
AB  - Flaxseed is increasingly being used in some food products because of its high
      content of alpha-linolenic acid and dietary fibre. However, flaxseed contains
      cyanogenic glycosides which release toxic hydrogen cyanide in the presence of
      water (autohydrolysis). A method for estimation of cyanide in flaxseed under
      these conditions is described. The determination is carried out by homogenizing
      the sample with water, letting it stand, filtering it through a membrane and then
      injecting the filtrate into an HPLC system consisting of an anion exchange column
      and an electrochemical (amperometric, oxidation) detector. The homogenate is
      analysed at various intervals until a maximum value of cyanide is observed. The
      cyanide content of ten cultivars of flaxseed, when analysed by this method, was
      found to range from 124 to 196 micrograms/g. The release of cyanide showed a
      maximum at about 3 h of hydrolysis. Virtually no cyanide was detected on boiling
      the homogenate or the flaxseed before determination.

PMID- 7589718
TI  - Average Swedish dietary intakes of organochlorine contaminants via foods of
      animal origin and their relation to levels in human milk, 1975-90.
AB  - The organochlorine contaminant (OCC) data generated by the Swedish National Food
      Administration (NFA) since 1973 has been utilized to calculate average Swedish
      dietary intakes. Direct food consumption statistics based on the yearly per
      capita Swedish consumption of five principal food groups has been used with OCC
      levels over 5-year periods, up to 1992. The present study shows the decline in
      OCC dietary intakes between 1975 and 1990. It is suggested that this is
      principally because of a decline in OCC concentrations in foods of animal origin
      rather than because of changes in food consumption patterns. The estimated
      intakes for the DDT complex, HCH isomers, dieldrin and HCB are generally well
      below the ADIs established by FAO/WHO. For total PCBs, no such ADI/TDI has been
      set up, either by FAO/WHO or in a Nordic PCB risk assessment. However, when
      compared with a US FDA guideline, the average Swedish total PCB dietary intake in
      1990 is approximately 10-fold lower. Finally, this study shows the good
      relationship between OCC dietary intakes via foods of animal origin and the
      concentrations measured on a fat weight basis in Swedish human milk.

PMID- 7589717
TI  - Screening procedure for organochlorine and organophosphorus pesticide residues in
      milk using matrix solid phase dispersion (MSPD) extraction and gas
      chromatographic determination.
AB  - A rapid technique for the extraction and gas chromatographic determination of
      five organochlorine and five organophosphorus pesticide residues in milk is
      described. Milk (5.0 ml) is blended with 2.0 g of C18 [octadecylsilyl-derivatized
      silica] and 1.5 ml acetonitrile in a syringe barrel. After the aqueous phase is
      removed from the column by vacuum aspiration, the pesticide residues are eluted
      from the C18/milk matrix with acetonitrile which is then eluted through a
      Florisil solid phase extraction (SPE) column. The acetonitrile is evaporated
      under nitrogen and the residue is dissolved in petroleum ether. This extract is
      directly analysed for organophosphorus pesticides by gas chromatography with
      flame photometric detection. After further clean-up of the extract on a mini
      Florisil column, the organochlorine pesticide residues are determined by gas
      chromatography with electron capture detection. Grade A homogenized and raw milk
      samples were fortified with five organochlorine and five organophosphorus
      pesticide residues. The average recoveries of fortified organochlorine pesticide
      residues (2.0-20 ppb) ranged from 76.0% to 97.8%. The average recoveries of
      fortified organophosphorus pesticide residues (10-50 ppb) ranged from 75.0% to
      104.5%. The MSPD and the AOAC International multiresidue method for pesticides in
      milk produced comparable results for milk samples containing incurred
      organochlorine pesticide residues. The use of the MSPD method results in a 90%
      reduction in organic solvent consumption and a 95% reduction in the hazardous
      waste generated when compared with the AOAC method.

PMID- 7589719
TI  - The effect of commercial processing on incurred residues of DDE in meat products.
AB  - The influence of processing on the degradation of DDE in meat products was
      investigated. First, the current level of contamination in six different types of
      Spanish meat products was determined. Analysis were carried out by capillary gas
      chromatography with electron capture detector. Of the three residues analysed
      (both o,p' and p,p' isomers of DDT, DDD, and DDE), only p,p'-DDE was found above
      the detection limit of 4 micrograms/kg fat. The frequency of p,p'-DDE detection
      for the various products investigated varied between 78 and 100% of the 129
      samples analysed, although mean levels were very low, in the range within 6-16
      micrograms/kg. No sample contained DDE residues above the EC maximum residue
      limit of 1 mg/kg for DDT and metabolites on meat products. Mean concentrations of
      DDE in Spanish meat products have declined since 1980 by more than 10-fold as
      compared with previously reported data. Meat products following three commercial
      processes were analysed to compare the levels of DDE in the finished products
      with those obtained in the starting material. The average levels of DDE remained
      unchanged after 30 days of curing in 26 samples of pork sausage. Similarly, mean
      DDE concentrations were essentially constant throughout the ripening process to
      which 30 hams were subjected. Finally, cooking in an oven (80-82 degrees C for
      100 min) of 20 pork bologna samples produced an apparent increase of 12.5% in
      mean p,p'-DDE levels that was not statistically significant (p > 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589720
TI  - Chemical and in vitro toxicological evaluations of water packaged in polyvinyl
      chloride and polyethylene terephthalate bottles.
AB  - This study proposed a new strategy assessing the health risks of mineral water
      packaging and compared the chemical analytical techniques and some in vitro
      cytotoxicological assays for the study of PVC and PET materials at the main
      stages of the manufacturing process of bottles. These evaluations were carried
      out with food simulant (deionized-endotoxin-tested water) and with natural
      mineral water in real conditions of packaging and storage (from 0 to 24 months).
      The complementarity of these two approaches is discussed. Some analytical and
      cytotoxic abnormalities were detected in the food simulant after contact with the
      batches of powdered PVC compound, PET resin and their intermediate steps of
      transformation (PVC-'paraison', PET-'perform'). But these results did not reflect
      the actual behaviour of the finished PVC and PET bottles, for which no major
      abnormality was detected in the natural mineral water.

PMID- 7589721
TI  - Effects of some insect growth regulators on growth of Aspergillus flavus and its
      productivity of aflatoxin B1 and lipids.
AB  - Two insect growth regulators, namely CME 134 and Dowco 439, have been tested for
      their effect on growth and on aflatoxin B1 and lipid productivity in Aspergillus
      flavus. No effect on growth and lipid production was detected. However, various
      concentrations of CME 134 and Dowco 439 showed significant inhibitory effects on
      aflatoxin B1 production. The degree of inhibition was dependent on the
      concentration and time of application. Inhibition was observed when Dowco 439 was
      added at inoculation and again 3, 6, 9, 12 and 15 days after inoculation, as well
      as after the addition of either CME 134 or Dowco 439 to the individual cultures
      at inoculation and 3 days after inoculation. However, the addition of either CME
      134 or Dowco 439 as late as 6 days after inoculation markedly decreased the
      inhibition of aflatoxin B1 production.

PMID- 7589722
TI  - Determination of ochratoxin A in beer.
AB  - Because of concern about possible transmission of ochratoxin A (OA) from
      contaminated grain adjuncts, development of a sensitive method for its
      determination in beer was investigated. Solid phase extraction (SPE) on C-18 and
      silica gel columns in series and on an immunoaffinity column (OchraTest) were
      used to obtain extracts for quantitation by reverse phase liquid chromatography
      with fluorescence detection. The standard curve was linear in the range 2.5-50 pg
      OA injected and detection limits for both methods were of the order 0.05-0.1
      ng/ml beer (signal to noise 3:1). Per cent recovery of OA from various beer
      samples spiked at a level of 1 ng/ml averaged 82-100% for three modifications of
      the SPE method and 97% for the immunoaffinity column method. Forty-one samples of
      Canadian and imported beers were analysed. Trace levels of OA (< or = 0.2 ng/ml)
      were detected in 26 samples by SPE and/or immunoaffinity column methods; there
      was generally good agreement between the methods. Identity of OA was confirmed by
      methyl ester formation in five samples cleaned up by the immunoaffinity column
      procedure.

PMID- 7589723
TI  - Beauvericin and fumonisin B1 in preharvest Fusarium moniliforme maize ear rot in
      Sardinia.
AB  - Six selected samples of preharvest maize ear rot, from different localities in
      Sardinia, Italy, were examined for causal Fusarium species and associated
      mycotoxins. All samples were almost exclusively found to be affected by Fusarium
      moniliforme, which was isolated from all infected ear sample kernels (100%). In
      two samples, in addition to F. moniliforme, F. proliferatum was also present but
      in a reduced percentage of kernels (up to 42%). All samples were found to be
      contaminated by fumonisin B1 (up to 250 mg/kg). Four samples were also found to
      be contaminated by beauvericin (up to 10 mg/kg), with higher concentration in
      samples also infected by F. proliferatum. When cultured on autoclaved maize
      kernels for 4 weeks at 25 degrees C, all 13 strains of F. moniliforme examined
      produced fumonisin B1 (up to 3750 mg/kg), whereas only three strains also
      produced beauvericin, but in very low amounts (5 mg/kg). In the same assay, four
      isolates of F. proliferatum also produced high amounts of fumonisin B1 (up to
      2500 mg/kg) but this was associated with higher concentrations of beauvericin (up
      to 175 mg/kg). This is the first indication of the production of beauvericin by
      F. moniliforme, as well as of its co-occurrence with fumonisin B1 in preharvest
      F. moniliforme maize ear rot.

PMID- 7589725
TI  - Scoliosis and spine deformities.

PMID- 7589724
TI  - Effects of temperature and mixing on polymer adjuvant migration to corn oil and
      water.
AB  - The effect of mixing on the migration of Irganox 1010 antioxidant from
      polypropylene and high-density polyethylene to water and corn oil was compared at
      77, 100, and 135 degrees C. Irganox 1010 migration to water is enhanced almost
      five-fold by mixing at 77 degrees C, whereas at 135 degrees C, mixing has only a
      nominal effect on migration. Irganox 1010 migration to corn oil is virtually
      unaffected by mixing at the temperatures studied. Migration data indicate a
      similar trend for Irganox 1076.

PMID- 7589726
TI  - Managed care: what is it? How will it affect long-term care?

PMID- 7589727
TI  - Repellent action of neem cream against mosquitoes.
AB  - Neem cream was used as mosquito repellent to provide protection against Aedes
      albopictus, Ae. aegypti, Culex quinquefasciatus, Anopheles culicifacies and An.
      subpictus mosquitoes. The application of neem cream on exposed body parts @2.0
      gm/person showed 78 (range 65-95), 89 (range 66-100) and 94.4 (range 66-100) per
      cent protection against Aedes, Culex and Anopheles mosquitoes respectively.
      Significant difference was observed between neem cream treated and untreated
      group of population for Aedes mosquitoes (p < 0.001). Application of neem cream
      was found to be a safe and suitable alternative to insecticide impregnated coils
      for personal protection against mosquitoes and one application was 68% effective
      for four hours.

PMID- 7589728
TI  - Anopheline fauna of Ajodhya hills, district Purulia. West Bengal.
AB  - Anopheline fauna of cattlesheds (CS) in Ajodhya hills, District Purulia,
      consisted of 12 species during summer, monsoon and 10 species during winter. Of
      the six vector species encountered in CS, Anopheles culicifacies, An. annularis,
      An. subpictus, An. maculatus and An. fluviatilis were found in all the three
      seasons. An. philippinensis was encountered in monsoon only and constituted 0.61%
      of the total anopheline catch made during the season. An. culicifacies was the
      most predominant species during summer (MHD 30.38) and monsoon (MHD 11) but
      ranked third (MHD 9.64) to An. annularis (MHD 16.28) during winter; An. subpictus
      being second (MHD 10.28) in order of predominance. An. annularis was the second
      most prevalent vector species in summer (MHD 21.38) and monsoon (MHD 9.92). The
      population density of the remaining three vector species was extremely low in the
      two seasons. In human dwelling (HD), of the five anopheline species encountered
      (An. subpictus, An. annularis, An. culicifacies, An. vagus and An. splendidus),
      the former three were found in all the three seasons. MHD of An. annularis in HD
      in summer, monsoon and winter was 3.7, 1.1 and 1.9 respectively, while MHD of An.
      culicifacies in the corresponding seasons was 5.01, 2.09 and 1.31 respectively.

PMID- 7589729
TI  - ABO blood groups among malaria cases from district Mandla, Madhya Pradesh.
AB  - A total of 2095 patients with fever were tested for malaria and classified
      according to ABO blood groups. Only 696 cases were malaria positive. While blood
      group A, B and O were equally susceptible to malaria infection, AB blood group
      had less number of persons with malaria parasites. A significantly lower
      frequency of Plasmodium falciparum was observed among individuals with blood
      groups A and O. In other two blood groups B and AB, no difference in P. vivax and
      P. falciparum proportions were observed. A two-year study showed that the
      frequency of repeated attacks between all blood groups was similar.

PMID- 7589730
TI  - Control of mosquito breeding using wood scrapings treated with neem oil.
AB  - Wood scrapings were given shape of a ball and soaked in 5, 10 and 20% neem
      (Azadirachta indica) oil diluted in acetone. Control of Anopheles stephensi and
      Aedes aegypti breeding in water storage overhead tanks (OHTs) with the
      application of these balls was achieved for 45 days. Two balls soaked in 5% neem
      oil produced the best results among other concentrations tested.

PMID- 7589731
TI  - Cerebral malaria in Jabalpur, India.
AB  - A total of 1783 patients were admitted in Govt. Medical College Hospital,
      Jabalpur with fever in 1993. Out of these 152 (8.5%) patients had cerebral
      malaria, of which 39 (25.6%) patients died. Age and sex-wise break-up indicated
      that males suffered more (p < 0.01) from malaria and majority of patients
      belonged to 16-40 yrs age-group. Mortality was significantly higher in patients
      with hyperparasitaemia, hypoglycaemia and delayed diagnosis and treatment.
      Comatose condition was the main determinant of death.

PMID- 7589732
TI  - Efficacy of two flowable formulations of Bacillus sphaericus against larvae of
      mosquitoes.
AB  - Laboratory evaluation revealed that the Spherimos and Vectolex formulations of
      Bacillus sphaericus produced 97 and 100% larval mortality respectively in Culex
      quinquefasciatus at a dose as low as 0.008 ml/sq m as against 93 and 97%
      mortality respectively at 1 ml/sq m in Anopheles stephensi. However, in An.
      culicifacies similar level of mortality was not observed even at 10 ml/sq m of
      these formulations. Field evaluation revealed 100% reduction of Cx.
      quinquefasciatus larvae for 2-3 weeks in pools and wells with single application
      of Spherimos @ 2 ml/sq m as against 95.4% reduction @ 10 ml/sq m in irrigation
      channel for one week. Vectolex @ 10 ml/sq m provided 99-100% reduction of Cx.
      quinquefasciatus larvae up to 9 weeks in wells and 1 week in channels.

PMID- 7589733
TI  - A study on the mosquito emergence from the underground sewerage system in some
      areas of Delhi.

PMID- 7589734
TI  - Prognostic factors in endometrial cancer.
AB  - OBJECTIVE: Most patients with endometrial carcinoma present with stage I disease
      and it is this group of patients in which prognostic factors have been studied,
      so that therapy can be tailored to the risks for recurrence. The papillary serous
      endometrial cancer and clear cell cancers have a poor prognosis but these
      comprise only a small proportion of endometrial cancer patients. The current
      surgical staging system for endometrial cancer is based on previously identified
      intra and extra-uterine factors that influence the prognosis. However, much of
      the information regarding prognosis, such as histologic type and grade, evidence
      of disease beyond the uterus and receptor-status can be gleaned from careful
      preoperative assessment of these patients. Information regarding ploidy and
      receptor status is available from curettage specimens and, with increasing use of
      hysteroscopy and/or vaginal ultrasound a more precise assessment of the extent of
      the disease in the uterine cavity and involvement of the cervix may be possible,
      although the uterine extent of the disease does not play the prognostic role that
      was anticipated formerly. A major concern regarding surgical staging has been the
      fact that many of these patients are elderly and obese with significant medical
      problems. There is the imminent risk that the pelvic and para-aortic node
      dissection (rather than sampling) may increase morbidity. More studies have shown
      that this might not be a factor with sampling. But does it suffice? Similarly,
      concerns have been expressed regarding those patients who may require
      postoperative radiation which may be compromised by postoperative adhesions,
      bladder, intestine and ureteral problems. It is yet to be demonstrated that in
      diseases extending outside the pelvis, the currently available treatment affects
      survival. Undoubtedly, recurrence patterns will be affected but clear
      demonstration of survival advantage is not available, eventually will never be.
      The concepts of treatment of advanced disease with spread outside the pelvis
      should undergo rethinking in the way that control of the existing disease rather
      than eradicating it by all means might offer better chances for life quality,
      life expectancy albeit limited, in cancer patients.

PMID- 7589735
TI  - Gynecologic cancer. Report of an international symposium on gynecologic oncology.
      Taiwan, April 29-May 1, 1994.

PMID- 7589736
TI  - Lymph node metastases, cell type, age, HPV status and type, neoadjuvant
      chemotherapy and treatment failures in cervical cancer.
AB  - Conflicting evidence on the prognostic influence of some of the clinical and
      histopathological variables in cervical cancer of the HPV status and type and
      chemotherapeutic response prompted a number of reviews from nearly 40 years
      experience in a tertiary referral centre. The collation and analyses of these
      data with those from recent literature allow some proposals to be made. The
      disease is more prevalent in the young women in whom, in many centers, the
      mortality is also higher; the latter may be related to the reported increase in
      both small cell types and adeno and adenosquamous carcinoma--a finding more
      marked in the young. Lymph node metastases, related to increasing grade, size,
      stage and lymph space invasion, are unequivocally associated with a worse
      prognosis. Resolution of the exact nature of the intimate association of this
      disease with the human papilloma virus remains to be resolved as does the
      influence on prognosis of the tumor HPV status and that of the different
      oncogenic types. Reports on the efficiency of neoadjuvant platinum based
      combination chemotherapy are generally promising but vary considerably depending
      on the regimen used. Its value will not be determined without properly conducted
      large randomized studies.

PMID- 7589738
TI  - Radioimmunodetection of human cervical carcinoma xenograft by 111In-labeled
      monoclonal antibody MAb Cx-99.
AB  - Radioimmunodetection (RAID) is more sensitive and specific than conventional
      diagnostic methods. In this study, a monoclonal antibody against cervical
      carcinoma antigen, MAb Cx-99, was labeled with 111Indium (111In). This
      immunoconjugate was intravenously injected into athymic nude mice bearing
      cervical squamous cell carcinoma (SCC) xenografts. The tissue distribution study
      showed that the xenograft tumor had higher binding activity than most other
      tissues after 48 h from injection, demonstrated by localization ratio of tumor of
      tissues (c.p.m./g) against blood (c.p.m./g). However, this localization ratio was
      also high in the liver, spleen and kidney. The imaging study by
      immunoscintigraphy also showed that the tumor and liver were distinct from other
      background tissues 2 days after injection. This preliminary study showed that
      111In-labeled MAb Cx-99 may have potential for RAID of cervical cancer,
      especially for tumors in the pelvis.

PMID- 7589737
TI  - Clinical evaluations of a new ovarian cancer marker, COX-1.
AB  - A monoclonal antibody was generated against an ovarian cancer cell line, OC-3-VGH
      and was shown to recognize a unique tumor-associated antigen, COX-1 found in
      ovarian or cervical tumors. COX-1 can be detected in the cultured shed medium of
      several ovarian/cervical cancer cell lines, and in the sera of ovarian or
      cervical cancer patients when assayed by a sandwich immunoassay kit employing
      this monoclonal antibody. Multi-medical centers clinical trials have been
      conducted since 1989 to evaluate the efficacy of using this immunoassay procedure
      for the cancer monitoring. In the case of ovarian cancer, COX-1 immunoassay kit
      has the sensitivity of 68% as compared to 71% for the corresponding CA 125 kit.
      When both COX-1 and CA 125 kits were combined for the simultaneous monitoring of
      cancer patients, the sensitivity could be increased to as high as 87%. Further
      analysis revealed that serum COX-1 levels in cancer patients are correlated with
      stages of tumor progression. Following the surgical removal of tumors, greater
      than 50% of the cancer patients showed dramatic and significant decrease of serum
      levels of COX-1 antigen. The results of these multi-center clinical studies
      clearly suggested that COX-1 is a suitable marker for the monitoring and
      diagnosis of ovarian cancer patients, when used alone or in combination with CA
      125.

PMID- 7589739
TI  - Modified pelvic anterior exenteration.
AB  - During a 20-year time period, 117 patients with various histologic types of
      cancer underwent pelvic exentereation. Six of the 107 patients who needed
      anterior exenteration with urinary diversion received partial excision of the
      urinary bladder and modification surgery, of which three had uretero-cystostomy,
      two had mobilization of bladder and uretero-cystostomy and one had uretero
      uterostomy. These six patients, except for two, died of disease in 1 year. Two
      patients are alive and happy, with quality of life because they can urinate
      normally. We suggest that anterior exenteration should be modified whenever
      possible to preserve the bladder and not to do an urinary diversion.

PMID- 7589740
TI  - Urogynecology and pelvic reconstructive surgery: office preoperative evaluation
      of the incontinent female.
AB  - Successful research outcomes in the treatment of genuine stress incontinence
      depend upon correct preoperative urodynamic evaluation. These procedures and how
      they are used for diagnosis and the selection of the correct surgical procedure
      are discussed.

PMID- 7589741
TI  - Multimodal treatment for the locally advanced stage IB, IIA, IIB patients of
      cervical cancer.
AB  - By employing neoadjuvent chemotherapy (NCT) before radical hysterectomy (RS) and
      pelvic radiotherapy (RT) in bulky locally advanced cervical cancer (IB, IIA,
      IIB), the study was focused to update the results of the author's therapeutic
      experience with multimodal treatment by observing tumor free survivals along with
      related prognostic factors in different treatment modalities with NCT. The
      chemotherapy regimen for induction is composed of Vinblastin, Bleomycin and cis
      Platin regimen (VBP). The effect of neoadjuvent chemotherapy was evaluated by the
      WHO definition of clinical response (CR, PR, ST, PG). As a result of NCT study in
      the stage IA, IIA, and IIB cervical cancer patients recurrence occurred in 50 out
      of 138 patients (35.5%) treated with radical hysterectomy only (RS) compared with
      17 out of 92 patients (18.5%) treated with NCT followed by radical surgery. In
      conjunction with the NCT study in the cervical cancer, another two groups of
      patients who were treated by neoadjuvent chemotherapy followed by radical
      hysterectomy (NCST) and adjuvent radiation (NCSRT) were evaluated in the high
      risk patients of cervical cancer with stage IB, IIA, and IIB. Primary responses
      in the NCST group (n = 61) were CR (68.9%), PR (22.9%), ST (4.9%) and PG (3.3%)
      respectively, while the chemoresponse of the NCSRT group (n = 101) were CR
      (65.3%), PR (18.9%), ST (4.9%) and PG (10.9%), respectively. The survival rates
      of the NCSRT group (n = 101) were 100% in all 1-5 years in CR group, while the
      rate of the NCST group was 100% at 1 year and 98.5% at 5 years in the CR group of
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589742
TI  - Clinical application of HPV typing in cervical cancer.
AB  - Certain human papaillomavirus (HPV) types are major risk factors for the
      development of cervical neoplasia. The value of HPV DNA testing in the management
      of patients with disease and in population screening is a subject of controversy.
      Since the introduction of molecular biology into the HPV field, there have been
      rapid advances and improvements in HPV diagnosis. The various molecular
      diagnostic methods for detection of HPV DNA (dot blot hybridization, Southern
      blot hybridization, in situ hybridization, Hybrid Capture Test, and polymerase
      chain reaction; PCR) could be selected by taking into consideration some factors
      such as characteristics of sample, sensitivity of HPV test and expenses. The HPV
      DNA testing would be a clinically useful diagnostic method, when used in
      conjunction with the Pap smear in population screening or in conjunction with
      cytology and colposcopy to identify the women infected with high-risk HPVs or
      women who had equivocal cervical lesions. Despite the confusion, a multitude of
      reports demonstrate that HPV DNA testing has the clinical utility, and future
      investigations should be directed at more accurately delineating its role in
      human health care.

PMID- 7589743
TI  - Intestinal complications of radiotherapy in gynecologic malignancy--clinical
      presentation and management.
AB  - Radiation therapy is an effective treatment modality for various gynecologic
      malignancies. In spite of advances in radiotherapy equipment and techniques over
      the years, the gastrointestinal and urinary tracts have remained a considerable
      problem with radiotherapy of the pelvis and abdomen. Clinical presentation of
      intestinal complications, current concepts of pathophysiology and principles of
      medical and surgical management are reviewed.

PMID- 7589744
TI  - Current views on the management of trophoblastic tumors.
AB  - Gestational trophoblastic disease has been recognized as a form of abnormal
      pregnancy as early as 1600 AD, and choriocarcinoma was the first cancer to be
      cured with chemotherapy even in the presence of distant and widespread
      metastases. Important advances in the past include the standardization of
      terminology, the concept of assignment of risk and the use of staging systems,
      the centralization of care and the establishment of regional registries, and of
      course the development of the radioimmunoassay for the beta subunit of human
      chorionic gonadotropin. The current views on the management of this disease
      recognizes the need for a multidisciplinary approach, with chemotherapy remaining
      at the forefront but also utilizing newer diagnostic techniques when necessary,
      and keeping in mind the crucial role that surgery can play especially in
      resistant cases. At the same time, the importance of basics such as careful
      follow up after evacuation of a hydatidiform mole cannot be overemphasized. There
      will be a continual refinement of the chemotherapy regimes used, and the aim is
      to achieve a similar level of response with decreased toxicity to the patient.

PMID- 7589745
TI  - Early de novo ovarian cancer and cancer developing in benign ovarian lesions.

PMID- 7589746
TI  - Obstetrics and gynecology in the next century.

PMID- 7589747
TI  - Intrapartum fetal pulse oximetry: present and future.
AB  - Pulse oximetry is widely used to monitor the patient's well-being in anesthetic
      and neonatal practice. As a result of recent technologic and theoretical
      advances, it has emerged as a clinical tool in intrapartum fetal monitoring.
      Oximeters record both pulse rate and arterial oxygen saturation of the fetus and
      they may be adapted to derive an estimate of peripheral perfusion. Reflectance
      oximetry is more accurate than transmission oximetry in intrapartum fetal
      management. This method uses the pulsatile changes of red and infrared light
      reflected from tissue to estimate arterial oxygenation. Pulse oximetry is cheap,
      non-invasive, simple to operate, relatively accurate and has a fast response
      time. Factors adversely affecting the accuracy of the pulse oximeter output
      include transducer displacement, peripheral vasoconstriction, hypotension,
      anemia, presence of intravascular dyes, meconium staining, fetal hair and scalp
      edema. Fetal pulse oximetry is limited by a wide normal range and inadequate
      calibration. The amniochorionic membranes however do not affect oximetry readings
      so that this method may be applied before rupture of the membranes, i.e. before
      labor. Once successfully developed, fetal pulse oximetry could potentially be
      used in combination with other monitoring techniques to reduce instrumental and
      operative interventions during labor and improve perinatal outcome.

PMID- 7589748
TI  - The outcome of placenta accreta in Kuwait (1981-1993).
AB  - OBJECTIVES: To study the demographic characteristics of patients with placenta
      accreta and to identify the clinical features, maternal and neonatal
      complications of this condition. METHODS: Sixteen cases of placenta accreta were
      identified in the Maternity Hospital of Kuwait during the period January 1981 to
      July 1993. Medical records were reviewed regarding past obstetric history, type
      of placenta, clinical presentation, maternal and fetal outcome. RESULTS: The rate
      of placenta accreta was found to be 98 per 1,000,000 deliveries. Emergency
      hysterectomy was needed in 87.5% of cases. There was one maternal death (6.25%)
      and three perinatal deaths (18.75%). Hemorrhage was the major presenting symptom
      either externally and antenatally in previa accreta or postpartum in accreta of
      the upper segment or internally in the same cases. The major postoperative
      complications were coagulopathy, urinary injury, pelvic hematoma and abscess, in
      addition to cardiac arrest. These complications, when considered separately, were
      not affected by a previous history of uterine scarring. CONCLUSIONS: Placenta
      accreta is a major cause of obstetric hemorrhage and has an adverse effect on
      maternal and neonatal outcome. It ought to be considered a possibility in
      patients with previous uterine scarring, placenta previa or retained placenta. It
      will remain a growing problem in the developing countries due to the rising
      incidence of previous multiple cesarean sections. Unfortunately the latter do not
      deter women in this part of the world from insisting upon having big families and
      refusing tubal ligation.

PMID- 7589749
TI  - The Dutch obstetric intervention study--variations in practice patterns.
AB  - OBJECTIVE: To compare obstetric intervention rates between Dutch hospitals.
      METHODS: A total of 28,934 hospital births under secondary care (specialist care
      for medium-/high-risk pregnancies) in 1990 were analyzed in a stratified, random
      sample of Dutch hospitals based on the records of the Dutch Netherlands perinatal
      database. Comparisons were made of the intervention rates between hospitals.
      RESULTS: The intervention rates of the various hospitals differed widely. The
      most striking difference was in the cesarean section (CS) rate for non-vertex
      first twins, with a range of 0-100% and a mean rate of 47.6%. On average a CS for
      a term breech was performed in 30.8% of cases and sedation or analgesics were
      administered in 16.2% of cases. The mean rate of episiotomy for a term breech was
      71.5%, the lowest rate being 18.8%. CONCLUSION: Our results show relatively low
      intervention rates with considerable interhospital variation.

PMID- 7589750
TI  - The partograph in the management of labor following cesarean section.
AB  - OBJECTIVE: To determine whether graphic labor record (partogram) can be used to
      predict the risk of uterine scar rupture in labor following lower segment
      cesarean section. METHODS: Between 1988 and 1991, 236 women had a trial of labor
      following cesarean section. After the onset of the active phase (3 cm cervical
      dilatation), a 1 cm/h line was used to indicate an alert line on the partogram.
      All the active phase partograms were divided into five time zones: A (area to the
      left of the alert line), B (0-1 h after the alert line), C (1-2 h after the alert
      line), D (2-3 h after the alert line), and E and F (> 3 h after the alert line).
      For the action line, different lag times after the alert line were defined
      according to the time zones. Sensitivity, specificity, cesarean section rates and
      rupture rates were calculated for the different lag times after the alert line,
      and a receiver-operating characteristic curve was constructed. RESULTS: Fifty
      five (23.3%) trials of labor ended in a repeat emergency cesarean. There were
      seven (2.9%) cases of scar rupture. Of the 181 vaginal deliveries, 151 (83%)
      occurred within 2 h after the progress of labor had crossed the alert line (zones
      A-C). Five out of seven cases of scar rupture occurred more than 2 h after the
      alert line had been crossed (zones D-F). The 2- and 3-h lag time after the alert
      line had a sensitivity of 71% and 43%, respectively, and a specificity of 78% and
      96%, respectively, in predicting uterine scar rupture. If cesarean sections were
      performed at 2 or 3 h after crossing the alert line, the projected cesarean rates
      would have been 36% and 27%, respectively. The scar rupture rates would in turn
      be 0.8% and 1.6%, respectively. CONCLUSION: In women undergoing a trial of labor
      following cesarean section, the partographic zone 2-3 h after the alert line
      represents a time of high risk of scar rupture. An action line in this time zone
      would probably help reduce the rupture rate without an unacceptable increase in
      the rate of cesarean section.

PMID- 7589751
TI  - Fetal transverse cerebellar diameter/abdominal circumference ratio in assessing
      fetal size.
AB  - OBJECTIVE: To test the usefulness of the fetal transverse cerebellar
      diameter/abdominal circumference (TCD/AC) ratio in predicting known small-for
      gestational-age (SGA) infants. METHOD: The relationship between fetal TCD and AC
      throughout the second half of pregnancy was investigated in 635 well-dated,
      normal pregnancies and examined with regard to gestational age and infant birth
      weight percentiles. RESULTS: One hundred eighteen (19%) fetuses were excluded due
      to inadequate visualization of the fetal cerebellum. A strong correlation was
      noted between gestational age determined by the last menstrual period and both
      fetal TCD (r2 = 0.91338) and AC (r2 = 0.89361) in fetuses with birth weights
      between the 10th and 90th percentiles (n = 407; mean 14.4, S.D. 1.2). Although
      the TCD/AC ratio showed a poor correlation with gestational age (r2 = 0.15788), a
      slight increase was noted during gestation. A TCD/AC ratio greater than 15.5 was
      present in 80% of SGA infants when measurements were performed within 1 week of
      delivery. CONCLUSION: Fetal TCD/AC ratio as a gestational age-independent method
      could improve diagnostic sensitivity and specificity in the early detection of
      fetal growth abnormalities.

PMID- 7589752
TI  - Vaginal hysterectomy following previous cesarean section.
AB  - OBJECTIVE: To determine whether hysterectomy by the vaginal route is safe and
      feasible in patients with previous cesarean section. METHODS: A retrospective
      study of the records of private and public hospital patients who underwent
      vaginal hysterectomy performed by the senior author. Two hundred twenty patients
      who had had previous cesarean sections were compared with a control group of 200
      patients who had not had previous pelvic surgery, with special reference to
      operative difficulties, intraoperative complications, surgical time and length of
      hospital stay. RESULTS: It was possible to perform vaginal hysterectomy safety in
      patients with previous cesarean sections. Three of 200 (1.5%) patients had
      inadvertent intraoperative urological trauma because of dense adhesions.
      CONCLUSIONS: The vaginal route is the route of choice for performing a
      hysterectomy in patients with previous cesarean section.

PMID- 7589753
TI  - Aspiration and tetracycline sclerotherapy for management of simple ovarian cysts.
AB  - OBJECTIVE: To evaluate the procedure of aspiration and tetracycline sclerotherapy
      in the management of simple ovarian cysts. METHODS: Twenty-five cases of simple
      ovarian cysts were subjected to cyst fluid aspiration and 5% tetracycline
      injection under ultrasound guidance. Cytological examination of the aspirated
      fluid was carried out in 24 cases and the patients were followed for 6-36 months.
      RESULTS: Cytology revealed a cellular sediment in 18 cases (simple cysts),
      follicular cells in four cases (follicular cysts), and blood and hemosiderin
      laden macrophages in two cases (endometriosis); subsequent surgery was required
      in only one case (endometriosis). CONCLUSIONS: The procedure of aspiration and
      tetracycline sclerotherapy was easy, safe and acceptable, with no recurrences. It
      appears to be a valid alternative to cyst aspiration in the management of simple
      ovarian cysts.

PMID- 7589754
TI  - Ultrasound evaluation of cervical shortening after loop excision of the
      transformation zone (LETZ).
AB  - OBJECTIVES: To assess cervical shortening after loop excision of the
      transformation zone (LETZ), and confirm the validity of ultrasound measurement of
      cervical length. METHODS: Subjects (n = 29) were patients at the colposcopy
      clinic of Beth Israel Hospital who underwent vaginal ultrasound measurement of
      cervical length before and after LETZ. The pathologic specimen was measured by
      ruler. Mean cervical length (+/- S.D.), mean percentage (+/- S.D.) of cervical
      length removed, and correlation (r) between ultrasound and pathology specimen
      measurement were determined. RESULTS: Mean (+/- S.D.) cervical length
      measurements prior to LETZ were 3.2 +/- 0.9 cm and after LETZ were 2.6 +/- 0.9
      cm, with a difference of 0.7 +/- 0.4 cm. The pathologic specimen (mean +/- S.D.)
      was 0.6 +/- 0.3 cm. The correlation between ultrasound and pathology measurement
      was r = 0.9 (p = 0.0001). Mean (+/- S.D.) cervical length was shortened by 22 +/-
      12%. CONCLUSIONS: There is excellent correlation between ultrasound and ruler
      measurement of the cervix. There is significant cervical length shortening after
      LETZ, but further study is needed to see whether this persists or leads to
      pregnancy complications.

PMID- 7589755
TI  - GnRH analog administration in patients with polycystic ovarian disease.
AB  - OBJECTIVE: To evaluate the hormonal response to the short protocol of
      gonadotropin-releasing hormone (GnRH) analog (GnRHa) in patients with polycystic
      ovarian disease (PCOD). METHODS: We enrolled 35 patients (20 infertile) with
      ultrasonographic and hormonal PCOD characteristics. GnRHa Suprefact was applied
      subcutaneously at a daily dose of 0.9 ml for 9 consecutive days starting on the
      10th-15th day after induced or spontaneous bleeding. Blood sampling for follicle
      stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol
      (E2), estrone (E1) and dehydroepiandrosterone sulfate (DHEA-S) was performed
      before the treatment and on days 3 and 4 of GnRHa administration. Student's t
      test was used for the analysis of differences between various mean values. All
      statistical analyses were performed by the computerized statistical package CSS
      Statistica. RESULTS: Pretreatment hormonal levels (FSH 5.68 +/- 1.86 IU/l, LH
      14.16 +/- 1.72 IU/l, E2 0.29 +/- 0.20 nmol/l, E1 0.35 +/- 0.17 nmol/l, T 3.52 +/-
      1.40 nmol/l, DHEA-S 7.15 +/- 2.89 mumol/l) barely differed on day 3 of GnRHa
      administration, except for the rise in LH (17.14 +/- 10.97 IU/l), which was still
      not significant. On day 9 of GnRHa application, significant suppression of FSH
      (3.16 +/- 1.55 IU/l) and LH (8.05 +/- 5.00 IU/l) was registered compared with
      pretreatment levels, without changes in the FSH:LH ratio, and in other parameters
      studied. Although there were no changes in ultrasound characteristics on day 9 of
      GnRHa administration compared with basal findings, bleeding occurred 14-18 days
      after the last GnRHa dose in 32 patients. There were three pregnancies out of 20
      infertile patients in the treated cycles. CONCLUSION: Significant suppression of
      FSH and LH in PCOD patients does not interfere with ovarian steroid production,
      which is probably maintained due to higher follicular sensitivity to normal FSH
      and LH levels. Alternatively it may be the consequence of the unaltered FSH:LH
      ratio in spite of GnRHa-suppressed absolute values. However the recommencement of
      menstrual bleeding and 15% of pregnancies in the investigated infertile patients
      suggest the occurrence of certain temporary intraovarian events, which probably
      continue after the cessation of GnRHa administration.

PMID- 7589756
TI  - Successful management of congenital protein C deficiency with recurrent pregnancy
      loss.
AB  - A 29-year-old woman experienced unexplained intrauterine fetal death (IUFD) three
      times, at 16, 27 and 27 gestational weeks. She was found to be protein C
      deficient and the existence of infarction in the placenta was suspected at 20
      weeks' gestation during her fourth pregnancy. Both heparin and antithrombin III
      were administered until delivery of a small-for-dates but live baby. Massive
      infarction in the placenta was evident at term. Anticoagulation with heparin is a
      useful treatment approach for cases of recurrent IUFD with protein C deficiency.

PMID- 7589757
TI  - Removal of levonorgestrel capsules from the biceps muscle.
AB  - Multiple levonorgestrel implants were identified and removed from below the
      biceps fascia using radiography to assist in localization, axillary block for
      anesthesia, careful dissection, and palpation of the implants within the deep
      muscle belly. This difficult implant removal demonstrates the importance of both
      a clinician experienced in levonorgestrel implant removal and a general surgeon
      experienced in arm surgery when performing such procedures.

PMID- 7589758
TI  - Intravaginal foreign body retained for a long duration.
AB  - An intravaginal foreign body of long duration can pose a diagnostic dilemma,
      since a number of diagnostic modalities may fail to detect its existence. We
      present the case of an 8-year-old girl who suffered from a bloody, malodorous
      vaginal discharge for over 4 years, during which time she had been evaluated by
      several gynecologists. A vaginal examination performed under analgesia revealed a
      pinpoint-sized opening 2 cm above the hymen. We inserted a cannula and injected
      radio-opaque contrast medium. An intravaginal filling defect was visible, which
      strongly suggested the presence of a foreign body. An incision through this
      scarred area was performed and two foreign bodies, one shaped like a plastic tube
      and the other a cap, were removed. We conclude that vaginography may provide an
      alternative diagnostic tool for this condition.

PMID- 7589759
TI  - Severe recurrent epistaxis causing antepartum fetal distress.

PMID- 7589761
TI  - ACOG technical bulletin. Preconceptional care. Number 205--May 1995. American
      College of Obstetricians and Gynecologists.
AB  - Preconceptional health care offers an important opportunity for practitioners
      involved in women's health to expand their primary care and prevention roles.
      Preconceptional counseling has been shown to benefit the fetus in various ways.
      Efforts to provide information may also lead to improvements in the patient's
      health.

PMID- 7589760
TI  - Liver transplantation and pregnancy.

PMID- 7589762
TI  - ACOG committee opinion. End-of-life decision making: understanding the goals of
      care. Number 156--May 1995 (replaces no. 38, June 1985). Committee on Ethics.
      American College of Obstetricians and Gynecologists.

PMID- 7589763
TI  - Modifications in the staging for stage I vulvar and stage I cervical cancer.
      Report of the FIGO Committee on Gynecologic Oncology. International Federation of
      Gynecology and Obstetrics.

PMID- 7589764
TI  - Comparison of the efficacy and safety of daily dosages of 6 mg and 20 mg
      dihydroergocristine in the treatment of chronic cerebro-vascular disease.
AB  - The efficacy and safety of two different regimens of dihydroergocristine, in the
      treatment of patients with chronic cerebro-vascular disease, were compared in
      this double-blind study. Forty out-patients, 11 males and 29 females, aged 55-80
      years were randomly assigned to treatment with 6 or 20 mg dihydroergocristine,
      daily, for 3 months. The Sandoz Clinical Assessment for Geriatrics (SCAG) scale
      was used to assess the efficacy of treatment. Both doses induced a statistically
      significant improvement (P < 0.01) in total SCAG scores after both 45 and 90 days
      of treatment. The higher dose produced a significantly greater improvement in
      total SCAG scores than did the lower dose after both 45 and 90 days. There were
      no statistically or clinically significant changes in any of the laboratory
      parameters after either treatment; neither were there any statistically
      significant changes in blood-pressure or pulse-rate except in the case of
      standing systolic pressure which decreased significantly (P < 0.01) in the 20 mg
      group. The only adverse event reported was a case of mild gastric pain at the end
      of treatment with 20 mg dihydroergocristine.

PMID- 7589766
TI  - Comparative evaluation of the antihypertensive efficacy of once-daily sustained
      release isradipine and lacidipine using 24-hour ambulatory blood-pressure
      monitoring.
AB  - In this single-blind crossover study the antihypertensive efficacies of two
      dihydropyridine calcium antagonists, sustained-release isradipine and lacidipine,
      were compared using clinic and ambulatory blood-pressure measurements. After a 2
      week placebo wash-out, 34 patients (19 men, 15 women, mean age 49 years) with
      mild to moderate hypertension (diastolic blood pressure range 95-110 mmHg) were
      treated with 5 mg sustained-release isradipine for 4 weeks and 4 mg lacidipine
      for 4 weeks in a random order. Medications were taken once daily at 08.00 h.
      Clinic and ambulatory blood pressures were recorded at the end of each placebo or
      treatment period. Two patients stopped isradipine and six lacidipine because of
      severe adverse effects. Clinic systolic and diastolic blood pressures decreased
      by an average of 17/14 mmHg with isradipine and 17/13 mmHg with lacidipine,
      compared with placebo (P < 0.01 in both cases), without a change in heart rate.
      Mean ambulatory 24-h and daytime systolic and diastolic blood pressure were
      significantly reduced by sustained-release isradipine and lacidipine (P < 0.05
      and P < 0.01, respectively). At night systolic blood pressure fell compared with
      placebo (P < 0.05 with both drugs) whereas the reduction in diastolic blood
      pressure was not statistically significant. Mean 24-h heart rate remained
      unchanged. Blood-pressure variability did not differ significantly between the
      two drugs or between either drug and the placebo. The antihypertensive effects of
      sustained-release isradipine and lacidipine were similar, but the tolerability of
      isradipine appears to be greater since it caused fewer withdrawals.

PMID- 7589765
TI  - Relationship between cardiosympathetic neuropathy and diabetic somatic neuropathy
      in patients with non-insulin-dependent diabetes mellitus.
AB  - The possibility of a relationship between diabetic somatic neuropathy and
      cardiosympathetic neuropathy was investigated in 103 patients with non-insulin
      dependent diabetes mellitus. Cardiosympathetic nerve function was assessed by
      myocardial scintigraphy. The severity of diabetic somatic neuropathy was
      determined by measuring the motor conduction velocities of the peroneal and
      tibial nerves and the sensory conduction velocity of the sural nerve. Analysis of
      the results did not show any correlations between the measures of
      cardiosympathetic nerve function and the measures of diabetic somatic neuropathy.
      The results indicate that diabetic somatic neuropathy and cardiomyosympathetic
      neuropathy develop independently in patients with non-insulin-dependent diabetes
      mellitus.

PMID- 7589767
TI  - Antihypertensive efficacy and safe use of once-daily sustained-release diltiazem
      in the elderly: a comparison with captopril. The Dilcacomp Study Group.
AB  - The efficacy and safety of sustained-release diltiazem, 200-300 mg once daily was
      compared with that of captopril, 12.5-25 mg twice-daily, in 100 elderly patients
      (65-85 years old) with mild to moderate essential hypertension (supine diastolic
      blood pressure 95-115 mmHg). All patients received placebo for 2 weeks, followed
      by an 8-week double-blind period, and were randomized to either diltiazem (n =
      50) or captopril (n = 50). Their blood pressure was measured at trough level at
      week 4 immediately before dosing, i.e. 24 h post diltiazem dose or 12 h post
      captopril dose. Also at week 4, in non-responders, diltiazem was increased from
      200 to 300 mg once daily and captopril from 12.5 to 25 mg twice daily to achieve
      a target supine diastolic blood pressure reduction of at least 10 mmHg or a
      diastolic blood pressure below 90 mmHg. Supine diastolic blood pressure, at week
      8, was significantly (P < 0.001) reduced from 102 +/- 1 to 90 +/- 1 mmHg with
      diltiazem and from 103 +/- 1 to 89 +/- 1 mmHg with captopril, bringing this
      parameter within normal limits for both groups. Supine systolic blood pressure
      was also significantly (P < 0.001) reduced. Target blood pressure was achieved in
      68% of patients taking diltiazem and in 70% taking captopril. Distribution of
      adverse events was comparable in both groups; no significant changes in
      laboratory or electrocardiographic parameters occurred. Two serious events were
      reported with captopril: one sudden death and one cerebrovascular stroke.
      Sustained-release diltiazem once a day is a convenient, well tolerated, first
      line treatment for hypertension in the elderly, for whom the possibility of using
      two dose levels allows a close regimen adjustment, 200 mg being recommended as a
      starting dose.

PMID- 7589768
TI  - Time-course of changes in the plasma-membrane lipid bilayer and cellular
      ultrastructure induced by tumour necrosis factor-alpha in K 562 and Daudi cells.
AB  - The time-course of changes in the plasma-membrane lipid bilayer induced by tumour
      necrosis factor-alpha (TNF) were investigated in cultured cells using spin-label
      electron-spin-resonance techniques. Treatment of K 562 cells, a human chronic
      myelocytic leukaemia cell line, in suspension culture with TNF for up to 6 h
      caused an initial increase in cell-membrane fluidity, which returned to the
      control level after 12 h of treatment. After 24 h of treatment, the cell-membrane
      fluidity had decreased and this decrease was maintained after 48 h of treatment.
      In Daudi cells, a human malignant lymphoma cell line, TNF, did not induce any
      changes in cell-membrane fluidity, indicating that the effect of TNF on membrane
      structure is cell-specific. The early and transient change in membrane fluidity
      in K 562 cells is probably related to signal generation, while the later,
      persistent change may reflect the phenotype of TNF-treated cells, in particular,
      changes in the plasma membrane-cytoplasmic complex. Histochemical electron
      microscopic studies indicated that the membrane fluidity changes induced by TNF
      have an ultrastructural correlate.

PMID- 7589769
TI  - High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease.
AB  - Rhesus haemolytic disease is a continuing problem in the newborn especially in
      countries where the use of anti-D immunoglobulin is not prevalent. The fetuses
      may need intrauterine transfusions to prevent hydrops faetalis and they also may
      need exchange transfusions to treat the hyperbilirubinaemia that develops after
      birth. These interventions expose the baby to several blood donors, hence the
      risk of infection and exchange transfusions. This study was performed to test
      whether the use of high-dose intravenous immunoglobulin soon after the birth of
      these infants reduced the need for exchange transfusions. After randomization,
      intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the
      treatment group. Nothing was given to the 19 controls. The number of exchange
      transfusions needed decreased significantly in the treatment group. No side
      effects of intravenous immunoglobulins were seen.

PMID- 7589770
TI  - Effects of low-dose oral contraceptive oestrogen and progestin on lipid
      peroxidation in rats.
AB  - Groups of six female rats were treated with low-dose oral contraceptive (0.667 mg
      progestin [norethisterone acetate] and 0.02 mg oestrogen [ethinyloestradiol]/kg
      body-weight), or its components, separately, at the same doses, for 6 weeks.
      Changes in liver and kidney levels of lipid peroxides (as indicated by
      malondialdehyde production), free fatty acids, superoxide dismutase, and catalase
      liver glutathione and serum ceruloplasmin compared with the untreated control
      group were studied. Combined oral contraceptive treatment produced a significant
      increase in the activity of catalase in the kidneys (P < 0.05). The levels of
      lipid peroxides, free fatty acids and glutathione in the liver, and of serum
      ceruloplasmin increased significantly with oestrogen treatment (P < 0.05). Lipid
      peroxides (in the liver only), and serum ceruloplasmin decreased significantly
      when progestin was administered (P < 0.05). The activities of superoxide
      dismutase and catalase decreased significantly in the oestrogen group (except for
      catalase in the kidney) but increased in the progestin group (P < 0.05). The
      results indicate that the components of the low-dose oral contraceptive may alter
      liver and kidney metabolism.

PMID- 7589771
TI  - Effect of an alpha-glucosidase inhibitor combined with sulphonylurea treatment on
      glucose metabolism in patients with non-insulin-dependent diabetes mellitus.
AB  - Ten patients with non-insulin-dependent diabetes mellitus who were being treated
      with a sulphonylureal compound but whose glucose metabolism needed further
      improvement were given a combination of their usual sulphonylurea treatment and
      an alpha-glucosidase inhibitor. Treatment with the alpha-glucosidase inhibitor
      (0.6 mg/day), in addition to glibenclamide (7.5 mg/day in two patients; 5.0
      mg/day in four; 2.5 mg/day in one) or tolbutamide (500 mg/day in three patients)
      for 4 weeks, improved hyperglycaemia after meals from 237-247 mg/dl to 192 mg/dl,
      and reduced glycosylated haemoglobin levels from 8.5-8.6% to 7.9% without causing
      hypoglycaemia.

PMID- 7589773
TI  - No effect of an alpha-glucosidase inhibitor on glucose metabolism in patients
      with non-insulin-dependent diabetes mellitus and low function of pancreatic beta
      cells.
AB  - Twenty patients with non-insulin-dependent diabetes mellitus who had been
      receiving appropriate dietary treatment for 3 months but whose glucose metabolism
      needed further improvement were treated with an alpha-glucosidase inhibitor.
      Treatment with the alpha-glucosidase inhibitor (0.6 mg/day) for 4 weeks, had no
      significant effect on blood glucose levels 2 h after breakfast or on glycosylated
      haemoglobin levels.

PMID- 7589772
TI  - The management of cystic fibrosis with carbocysteine lysine salt: single-blind
      comparative study with ambroxol hydrochloride.
AB  - The effectiveness of carbocysteine lysine salt monohydrate (SCMC-Lys) and
      ambroxol hydrochloride (ABX) in the management of respiratory impairment was
      compared in a single-blind, randomized study of 26 cystic fibrosis patients with
      similar baseline characteristics. Adults received either SCMC-Lys 900 mg or ABX
      33 mg three times a day and children under 14 years of age either SCMC-Lys 270 mg
      three times a day or ABX 10 mg four times a day. All treatments were given orally
      for 80 days and at the end of this control period both groups showed significant
      improvement in chest sound score but improvement in cough score was observed only
      in those receiving SCMC-Lys. Expectorate viscosity and elasticity decreased
      significantly in both groups. In SCMC-Lys-treated patients paCO2 decreased and
      paO2 and Hb O2 saturation increased while only paO2 increased significantly in
      those treated with ABX. An increase in tidal volume, peak expiratory flow values
      and forced expiratory volume were evident in those receiving SCMC-Lys while
      significant increases in forced expiratory flow were recorded in those receiving
      ABX. SCMC-Lys patient's Shwachmann index improved significantly and conversely to
      the ABX patients. No adverse events were recorded in either treatment group. The
      study concluded that SCMC-Lys is at least as effective as ABX in improving
      respiratory function in patients with cystic fibrosis.

PMID- 7589774
TI  - Prostaglandin E1 increases indocyanine green disappearance rate in patients with
      chronic liver disease.
AB  - The plasma disappearance rate of indocyanine green was examined after
      prostaglandin E1 administration in 11 patients with chronic liver disease. The
      patients were divided into two groups according to the presence (n = 6) or
      absence (n = 5) of liver cirrhosis. Indocyanine green (0.1 mg/kg) was introduced
      as an intravenous bolus 5 min after prostaglandin E1 administration and the
      disappearance rate of indocyanine green (ICG-K) was determined by a finger
      monitoring method. Saline was injected as the control. Prostaglandin E1
      administration increased ICG-K, and this response was dose dependent when the
      prostaglandin E1 dose ranged from 0.01 to 0.05 micrograms/kg/min. When ICG-K
      after prostaglandin E1 relative to the ICG-K after saline (the control) was
      defined as the ICG-K ratio, the ICG-K ratio in the liver cirrhosis group was
      higher than that in the group without cirrhosis. These findings suggest that
      prostaglandin E1 increases the ICG-K of patients with chronic liver disease, and
      that this is strongest in patients with liver cirrhosis.

PMID- 7589775
TI  - Treatment of chronic hepatitis C with interferon-alpha: sustained absence of
      hepatitis C virus RNA from serum after four courses of therapy.
AB  - A patient with chronic hepatitis type C, confirmed by the detection of hepatitis
      C virus RNA (HCV RNA) in the serum and by histological examination of the liver
      biopsy specimen, was treated with four courses of interferon-alpha (IFN-alpha).
      For the first three courses of IFN-alpha the patient's serum alanine
      aminotransferase (ALT) level normalized during the administration of IFN-alpha
      but rose again after its cessation; similarly, HCV RNA was absent from the serum
      by the end of each course of treatment but could be detected once again after
      treatment stopped. The fourth course of IFN-alpha therapy, however, produced a
      sustained normalization of the ALT level and sustained absence of HCV RNA from
      the serum for 20 months after the end of treatment. This case suggests that
      patients with the potential for an eventual complete response to IFN-alpha
      therapy may show a normalization of serum ALT levels during IFN-alpha
      administration and the absence of HCV RNA in the serum by the end of each course
      of treatment (even if that particular course of treatment does not produce a
      sustained response).

PMID- 7589776
TI  - Human estrogen receptor messenger RNA variants in both normal and tumor breast
      tissues.
AB  - By using the PCR-SSCP technique we characterized various ER-specific RNA species
      present in a series of primary breast cancers, as well as in cell lines
      established from breast carcinomas and in mammary gland tissues from healthy
      specimens. A series of six truncated messenger RNAs generated by alternative
      splicing was characterized. These RNAs correspond to specific deletions of one
      (exons 2-7, except exon 6) or two (exons 3 + 4) exons. All these RNA variants are
      observed in each one of the analyzed RNAs, regardless of origin. In addition, the
      relative amount of these different variants in ER + tumors is comparable to that
      measured in ER - tumors and healthy mammary gland tissues. This data suggests
      that tumor progression is not related to the emergence of any of the ER mRNA
      variants.

PMID- 7589777
TI  - Production and secretion of N-terminal secretogranin II derived peptides in GH3B6
      prolactin cells.
AB  - Chromo/secreto-granins are proteins specific of neuroendocrine cells.
      Chromogranin B (CgB) and secretogranin II (SgII) are both present in normal and
      in tumoral (GH3B6) prolactin cells, in which they are colocalized in the same
      secretory granules. These proteins contain multiple dibasic cleavage sites and
      are considered as potential precursors of active peptides, though their exact
      function remains unknown. SgII is sulfated on tyrosine-126. We took advantage of
      this feature to study its post-translational processing in anterior pituitary
      cells in primary culture and in GH3B6 cells. Pulse-chase experiments with
      [35S]sulfate demonstrated the precursor-product relationship between SgII and
      four N-terminal-derived peptides. Kinetic experiments showed the sequential
      cleavage of SgII from the C-terminus to the N-terminus. Mature SgII and the
      derived peptides were secreted by both cell models, and their release was
      stimulated by TRH (30 nM), a secretagogue of prolactin. These data show that SgII
      is proteolytically processed into different secreted peptides in prolactin cells
      and demonstrate that GH3B6 cells provide a good cell model for studying the
      maturation of SgII in anterior pituitary.

PMID- 7589779
TI  - Identification of a composite steroid hormone response element on the human
      placental lactogen promoter.
AB  - Three regions of the human placental lactogen (hPL) promoter that contain several
      half-site motifs that closely resemble the responsive elements for thyroid
      hormone (TR), all trans retinoic acid (RAR) and 1,25 dihydroxyvitamin D3 (VDR)
      have been identified and characterized. Transfection studies in BeWo
      choriocarcinoma cells indicate that site A (nt -979 to -954) is responsive to RAR
      alpha but not TR beta. Site B (nt -1140 to -1170) is responsive to both RAR alpha
      and TR beta, and site C (nt -550 to -580) is not responsive to either RAR alpha
      or TR. These findings, together with the observation that placental cells express
      retinoid receptors and TRs, strongly suggest a role for these receptors in the
      regulation of the hPL gene. Site B on the hPL promoter is able to integrate the
      responses to RA and T3 through a single element.

PMID- 7589778
TI  - Androgen-independent effects of prolactin on the different lobes of the immature
      rat prostate.
AB  - In this study, we have examined the respective roles of androgens and prolactin
      (Prl) on rat prostate development and function. Hypophysectomized immature rats,
      castrated or not after hypophysectomy and treated or not with a 5 alpha-reductase
      inhibitor, were used to study the different aspects of Prl action on the rat
      prostate and its synergy with androgens in vivo. Using Northern blot analysis and
      quantitation of prostatic mRNAs, we have shown that Prl significantly increases
      the steady-state levels of transcripts coding for several lobe-specific proteins:
      the C3 subunit of prostatein, probasin, and RWB. We have confirmed these
      observations in vitro, on explants of immature rat prostate treated with either
      saline, Prl, or testosterone. In addition, we have demonstrated by a nuclear run
      on assay that Prl significantly enhances the transcription rate of the C3 gene in
      the rat prostate. We conclude that the effects of Prl concern all lobes of the
      organ and are, at least in part, androgen-independent. Moreover, Prl is able, via
      an androgen-independent pathway, to increase the rate of transcription of the C3
      gene, one of the major products of the rat prostate.

PMID- 7589780
TI  - Desethylamiodarone is a competitive inhibitor of the binding of thyroid hormone
      to the thyroid hormone alpha 1-receptor protein.
AB  - Desethylamiodarone (DEA), the major metabolite of the potent antiarrythmic drug
      amiodarone, is a non-competitive inhibitor of the binding of thyroid hormone (T3)
      to the beta 1-thyroid hormone receptor (T3R). In the present study, we
      investigated whether DEA acts in a similar way with respect to the alpha 1-T3R.
      The chicken alpha 1-T3R, expressed in an E. coli system, was incubated in the
      presence or absence of DEA with [125I]T3 in buffer containing 0.05% Triton X-100,
      0.05% BSA and 1% ethanol (v/v) in order to solubilise DEA. DEA, but not
      amiodarone, inhibited T3 binding in a dose-dependent manner; the IC50 value was
      3.5 x 10(-5) M. Scatchard analyses in the presence of DEA demonstrated a dose
      dependent decrease in Ka values, but no change in MBC. Lineweaver-Burk plots
      clearly indicated competitive inhibition by DEA. Pre-incubation of the alpha 1
      receptor with DEA decreased maximal [125I]T3 binding, which was independent of
      the duration of pre-incubation. In conclusion, in contrast to the beta 1-T3R,
      where DEA acts as a non-competitive inhibitor, we now report as a new finding the
      competitive action of DEA to the alpha 1-T3R.

PMID- 7589781
TI  - The lutropin beta-subunit N-terminus facilitates subunit combination by
      offsetting the inhibitory effects of residues needed for LH activity.
AB  - Human chorionic gonadotropin (hCG) contains a beta-subunit N-terminal amino acid
      extension that contacts the alpha-subunit and is needed for efficient alpha and
      hCG beta-subunit combination. Here we report that an hCG beta-subunit analog,
      lacking residues 2-8, combined with the alpha-subunit more efficiently when
      positively charged residues between beta-subunit cysteines 10 and 11 were
      replaced with negatively charged residues found in the corresponding portion of
      follitropin. Residues 2-8 had no influence on binding of hCG to lutropin
      receptors. Positive charges between cysteines 10 and 11 are essential for high
      affinity binding of lutropins to their receptors. Therefore, the N-terminal
      extension found in all lutropin beta-subunits appears to have evolved to offset
      the inhibition of subunit combination by beta-subunit residues that are essential
      for lutropin activity. This beta-subunit extension is not found in follitropins
      or thyrotropins, hormones that have negatively charged residues between cysteines
      10 and 11.

PMID- 7589783
TI  - Estrogen action in target cells: selective requirements for activation of
      different hormone response elements.
AB  - RENE1 cells, an estrogen receptor positive rat uterine endometrial cell line
      immortalized with the E1A oncogene, were analyzed for the presence of estrogen
      dependent signal transduction pathways using the induction of transfected as well
      as endogenous genes. RENE1 cells express the estrogen receptor as analyzed by
      Northern blots and ligand binding assays (40 fmoles/mg protein). The receptor
      system appears functional, based on the induction of reporter constructs
      containing the consensus estrogen response element (ERE) in transient
      transfection assays and alterations in endogenous transcripts visualized by
      utilizing differential display methodology. However, neither transfected repoter
      constructs containing the c-fos ERE, nor the endogenous c-fos, c-jun, or c-myc
      genes are induced by estrogens in these cells despite being induced by estrogens
      in the uterus in vivo. In addition, estradiol did not induce endogenous c-fos
      expression or the activity of CAT reporters containing the c-fos ERE in a stable
      transfectant of RENE1 cells with a 3-fold elevation in estrogen receptor content.
      Under identical conditions, TPA and serum rapidly induce c-fos transcription in
      RENE1 cells, indicating that the lack of inducibility by estradiol is not due to
      a general inhibitor of transcription of these genes. These results suggest that
      RENE1 cells lack factors present in normal uterine cells which are required for
      the estrogenic induction of a specific subset(s) of EREs. These observations
      support the generally evolving hypothesis that steroid hormones may act through
      composite response elements via interactions with other transcription factors, in
      addition to functioning as homodimers at classical palindromic response elements.

PMID- 7589782
TI  - Multifactorial regulation of pituitary adenylate cyclase-activating polypeptide
      (PACAP)-induced production of cyclic AMP in ATT-20 corticotrophs: major
      involvement of Rolipram-sensitive and insensitive phosphodiesterases.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) appear to play a major role in the
      modulation of cellular accumulations of cAMP/cGMP and hence the magnitude of the
      cell response to a hormone signal. These enzymes are present in cells as multiple
      isoforms and lie under control of various protein kinases. Because PACAP, unlike
      corticotropin-releasing factor (CRF), may stimulate a dual signalling pathway in
      pituitary cells (activating both adenylyl cyclase and phospholipase C), we used
      AtT-20 corticotrophs and primary cultures of rat pituitary cells to study the
      effect and possible differential influence of these peptides on cAMP formation.
      Time-course analysis indicated that, both in the absence and the presence of
      Rolipram (a selective type IV PDE inhibitor), PACAP stimulated a rapid and short
      lived accumulation of cAMP in tumor corticotrophs, while in the presence of the
      non-selective inhibitor IBMX, the peptide produced a sustained high plateau level
      of second messenger (10 times the level generated with Rolipram at 20 min). On
      the contrary, when exposed to CRF, cAMP production augmented in parallel,
      irrespective of whether Rolipram or IBMX were present. The differential effects
      of the PDE inhibitors were seen with PACAP concentrations ranging from 0.1 to 100
      nM, and could also be demonstrated in primary cultures of pituitary cells. Co
      incubation of AtT-20 cells with Rolipram along with inhibitors of type I (but not
      of type III) PDEs, enhanced cAMP formation elicited by PACAP to a level
      significantly higher than that induced by CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589784
TI  - Testosterone stimulates the biosynthesis of m-aconitase and citrate oxidation in
      prostate epithelial cells.
AB  - Mitochondria (m-)aconitase is a rate-limiting regulatory enzyme in prostate
      epithelial cells which minimizes citrate oxidation by these cells. This unique
      metabolite characteristic is responsible for the ability of the prostate to
      accumulate and secrete extraordinarily high levels of citrate. Testosterone is a
      major regulator of prostate growth and function, and stimulates citrate
      oxidation. Therefore, an important action of testosterone might be its
      stimulation of m-aconitase in prostate epithelial cells. Studies were conducted
      with rat ventral prostate (VP) epithelial cells to establish the effect of
      testosterone on the level of m-aconitase and corresponding citrate oxidation.
      Physiological concentrations (10(-7)-10(-10) M) of testosterone in vitro markedly
      increased the level of m-aconitase in freshly prepared isolated prostate
      epithelial cells. This increase was apparent within 3 h of exposure to the
      hormone. The stimulatory effect of testosterone on m-aconitase was abolished by
      actinomycin D and by cycloheximide. Both the level of m-aconitase enzyme and the
      level of m-aconitase activity were similarly increased by testosterone treatment.
      Correspondingly, testosterone increased the rate of mitochondrial citrate
      oxidation while having no effect on the rate of isocitrate oxidation, thereby
      demonstrating that the action of testosterone is specifically targeted at the m
      aconitase reaction. In vivo studies revealed that castration markedly decreased
      and testosterone administration increased the m-aconitase level of prostate
      epithelial cells. In contrast, neither liver nor kidney m-aconitase level was
      altered by castration. These studies demonstrate that testosterone regulates the
      biosynthesis of m-aconitase in prostate epithelial cells.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7589785
TI  - Human fetal adrenal hydroxysteroid sulphotransferase: cDNA cloning, stable
      expression in V79 cells and functional characterisation of the expressed enzyme.
AB  - Dehydroepiandrosterone sulphate (DHEAS) is a major adrenal secretory product,
      particularly in the fetus where it serves as a substrate for oestrogen
      biosynthesis by the placenta. The enzyme in the adrenal responsible for
      synthesising DHEAS, hydroxysteroid sulphotransferase (HST), is therefore
      essential for human development. We have isolated a full-length cDNA clone,
      encoding human fetal adrenal HST, and constructed a stable cell line expressing
      it by transfection into V79 Chinese hamster lung fibroblast cells. This cDNA was
      essentially identical to that isolated from adult human liver, where the role of
      HST is less well understood. This recombinant cell line allowed determination of
      the substrate specificity and kinetic properties of this enzyme towards various
      steroid hormones, and by comparison of these activities with human liver cytosol
      we have shown that HST is the major sulphotransferase responsible for the
      sulphation of DHEA, androsterone and pregnenolone in man and that, functionally,
      the hepatic and adrenal enzymes are very similar. The expressed HST was also
      active with testosterone, cortisol (although at low levels) and the xenobiotic 17
      alpha-ethinyloestradiol, but not with oestrone or 1-naphthol. We have therefore
      created a valuable resource for the study of this important enzyme.

PMID- 7589786
TI  - Characterization of a rat type 2 angiotensin II receptor stably expressed in 293
      cells.
AB  - A cDNA clone for the rat type 2 (AT2) angiotensin II receptor was stably
      transfected into human embryonic kidney 293 cells. Binding characteristics of
      CGP42112A (Kd = 0.18 nM, Bmax = 10.8 pmol/mg protein) and ligand specificity were
      indistinguishable from those obtained with the whole rat fetus and with
      transiently transfected COS-7 cells. Non-hydrolyzable guanine nucleotide analogs
      did not affect the ligand binding curve; interestingly, the guanine nucleotide
      analog's effect was observed in the presence of sulfhydryl reducing agent,
      suggesting that a certain redox condition may affect G protein coupling to this
      receptor. Using the established cell line, several second messenger systems were
      assessed. None of cAMP levels, cGMP levels, arachidonic acid release, or
      phosphotyrosine phosphatase activity was affected by angiotensin II stimulation
      of this receptor. Furthermore, the AT2 receptor did not undergo agonist
      stimulated internalization. These results using the cloned receptor suggest that
      the transfected AT2 receptor fails to effectively couple to the major G protein
      mediated signaling mechanisms and ligand-activated internalization in transfected
      293 cells.

PMID- 7589787
TI  - Possible involvement of microfilaments in the regulation of Sertoli cell
      aromatase activity.
AB  - Recent observations indicate that Sertoli cell aromatase activity decreases when
      cultures are performed at high density. Increasing cell density modifies cell
      shape in culture from flat cells with visible anchorage sites and abundant
      intercellular spaces to cells with higher profiles that form a uniform epithelial
      sheet with no intercellular spaces. Changes in cell architecture are associated
      with reorganization of the cytoskeleton components. In this report, we have
      tested whether disruption of microfilaments and microtubules by cytochalasin B
      and colchicine, respectively, has any effect on the ability of FSH to stimulate
      aromatase activity. Cytochalasin B, but not colchicine, significantly enhanced
      aromatase activity in FSH and dbcAMP stimulated cells. The increase in aromatase
      activity was accompanied by a striking change in cell morphology. Time course
      studies suggested that microfilament organization is involved in some metabolic
      event which occurs sometime between 2 and 4 h after the initial steps of FSH
      action. The reversibility of the biochemical and morphological changes induced by
      cytochalasin B was demonstrated. The effect of cytochalasin B was observed in
      high but not in low-density cultures, suggesting that microfilament organization
      in high-density cultures constrains FSH stimulation of aromatase activity. The
      last two observations made suggest the existence of a dynamic interplay between
      microfilament organization and FSH action in Sertoli cells.

PMID- 7589789
TI  - Study of TTF-1 gene expression in dog thyrocytes in primary culture.
AB  - TTF-1 is a homeodomain-containing transcription factor mainly expressed in the
      thyroid where it controls the tissue-specific expression of the thyroglobulin,
      thyroperoxidase and TSH receptor genes. It is therefore potentially implicated in
      the hormonal control exerted by thyrotropin via the second messenger cyclic AMP
      on the transcription of these genes in thyrocytes. In order to investigate
      whether there exists a relationship between the stimulation of the cAMP pathway
      and TTF-1 gene expression in these cells, we have compared the amounts of TTF-1
      protein, its state of phosphorylation and its subcellular distribution in control
      and cAMP-stimulated dog thyrocytes in primary culture. Dog TTF-1 was expressed in
      bacteria as a fusion protein and antibodies were raised against the dog TTF-1
      moiety. Stimulation of the thyrocytes by cyclic AMP agonist only marginally
      increased TTF-1 gene expression as shown for the mRNA by RNase protection assay
      and for the protein by immunoblotting and immunoprecipitation of extracts from
      35S-methionine labelled cells. The phosphorylation state of TTF-1 was
      investigated by immunoprecipitation of extracts from 32P-labelled thyrocytes.
      Phosphorylation level appeared to be essentially unaffected by forskolin
      treatment of the cells. We also looked for differences in the use of
      phosphorylation sites by partial proteolytic digestion of immunoprecipitated 32P
      labelled TTF-1 with Glu-C and Asp-N endoproteases. Comparison of radioactivity
      distribution amongst the generated fragments did not reveal any difference in the
      pattern of TTF-1 phosphorylation in control and forskolin conditions. Lastly, in
      situ detection of TTF-1 by immunofluorescence demonstrated that the protein was
      localized in the nucleus of the cells, irrespective of the culture conditions. No
      major change in TTF-1 gene expression upon stimulation of the thyrocyte with a
      cAMP agonist could thus be detected in this study. The absence of an obvious
      modification of the TTF-1 protein itself in response to cAMP stimulation may
      indicate that other transcription factor(s) or co-factor(s) are involved in the
      control exerted by cAMP on the expression of thyroid-specific genes.

PMID- 7589788
TI  - Influence of Hepes- and CO2/HCO(3-)-buffer on Ca2+ transients induced by TRH and
      elevated K+ in rat pituitary GH4C1 cells.
AB  - The influence of two buffer systems (Hepes and CO2/HCO3-) on intracellular Ca2+
      ([Ca2+]i) transients evoked by TRH and by elevated K+ were studied in single, and
      small clusters of, clonal rat pituitary GH4C1 cells using Fura 2. The steady
      state level of [Ca2+]i was virtually identical in Hepes and CO2/HCO3-. In both
      buffers, addition of TRH induced a transient increase in [Ca2+]i which attained a
      significantly higher peak in Hepes (357 +/- 43 nM) when compared with values
      measured in the presence of CO2/HCO3- (184 +/- 21 nM). In Hepes, the basal IP3
      level was higher than in CO2/HCO3-. The TRH-evoked increase in IP3 was higher in
      magnitude in Hepes than in CO2/HCO3-, although the stimulated/basal ratio was not
      different between the two buffers. The buffer composition had no effect on the
      specific binding of 3H-TRH to the cells. Furthermore, the amplitude of the
      increase in [Ca2+]i evoked by 50 mM K+ was identical in both buffers. TRH and K+
      had no effect on pHi in either buffer. The present results indicate that HCO3-
      has an influence on TRH-induced Ca2+ transient, at least in part by modifying the
      TRH-evoked production of IP3.

PMID- 7589790
TI  - Administration of growth hormone modulates the gene expression of basic
      fibroblast growth factor in rat costal cartilage, both in vivo and in vitro.
AB  - We examined the effect of growth hormone on local growth factor mRNA expression
      in male Sprague-Dawley rats. Repetitive systemic administration of growth hormone
      (0.4 IU every 4 h) increased the expression of IGF-I mRNA up to 2.8-fold in
      costal cartilage tissue compared with controls. Basic FGF (bFGF) mRNA expression
      gradually increased up to 15.5-fold compared with pre-injection samples, where
      the mRNA expression was 5.3-times greater than vehicle-injected controls. TGF
      beta mRNA showed little changes. Moreover, one microgram/ml of growth hormone
      enhanced the expression of bFGF mRNA in costal chondrocytes in culture. We
      conclude that growth hormone increased the local expression of bFGF, as well as
      that of IGF-I, in cartilage, and suggest that bFGF is directly regulated by
      growth hormone within a local area.

PMID- 7589791
TI  - The in vivo expression of the FGF receptor FREK mRNA in avian myoblasts suggests
      a role in muscle growth and differentiation.
AB  - Muscle growth during embryogenesis is the result of a balance between the
      proliferation of myoblasts and their differentiation into mature, contractile
      fibers. Fibroblast growth factors (FGFs) are potent stimulators of myoblast
      proliferation and inhibitors of myoblast differentiation in vitro. However, it is
      not clear at present if FGFs and their receptors regulate this process in vivo,
      partially because no FGF receptor was known to be expressed by myoblasts during
      embryogenesis. In this study, we have used quail/chick grafting and BrdU labeling
      techniques to demonstrate that a recently cloned avian FGF receptor, FREK, is
      expressed by replicating skeletal muscle myoblasts, while differentiated muscle
      cells no longer express this receptor. In the limb, muscle progenitors
      originating from the somite start expressing FREK at 3 days of development (E3).
      FREK expression in the limb myoblasts follows that of Pax-3 and Pax-7, but
      precedes that of MyoD. Since MyoD expression signals the onset of terminal
      differentiation, this demonstrates that FREK is expressed in muscle progenitors
      prior to overt muscle differentiation. A more complex situation is observed in
      the trunk region, where a first wave of MyoD-positive myocytes, which are
      postmitotic and never express FREK, appear in the early myotomal compartment of
      the somite. Slightly later, at E2.5, FREK-positive myoblasts migrate into the
      myotome as a second wave of muscle progenitors, 15 hr after the first MyoD
      positive cells. FREK's expression by myoblasts arising at all stages of
      myogenesis indicates that this growth factor receptor represents one of the
      earliest molecular markers for this cell population. FREK's prominent expression
      during muscle differentiation sets it apart from other FGF receptors and suggests
      that this molecule plays an important role during muscle growth and
      differentiation.

PMID- 7589792
TI  - beta-Catenin has Wnt-like activity and mimics the Nieuwkoop signaling center in
      Xenopus dorsal-ventral patterning.
AB  - beta-Catenin is a protein known to associate with the cytoplasmic domains of
      members of the cadherin family of cell adhesion molecules. Recently, Funayama et
      al. (Funayama et al. (1995). J. Cell Biol. 128, 959-968.) demonstrated that
      overexpression of beta-catenin causes the formation of a secondary axis in Xenpus
      laevis embryos. In order to understand the role of beta-catenin in axis
      formation, we examined its biological activity in further detail. beta-Catenin is
      effective at inducing a secondary axis when overexpressed in the vegetal ventral
      region of early cleavage stage (4-32 cell) embryos. beta-Catenin may act as part
      of the Nieuwkoop center because cells overexpressing beta-catenin do not
      contribute directly to axial structures. Overexpression of beta-catenin can
      specify de novo axis formation, as shown by its ability to rescue UV-ventralized
      embryos. Overexpression of beta-catenin alone is not sufficient to cause
      elongation of animal caps or to induce mesodermal markers in animal caps. In
      these assays, overexpression of beta-catenin behaves like ectopic expression of
      certain members of the Wnt gene family. Like Wnts, overexpression of beta-catenin
      was also found to increase gap junctional communication in cells of the ventral
      animal cap. Overexpression of beta-catenin causes a small increase in the rate of
      aggregation of Xenopus blastomeres. Overexpression of C-cadherin causes a more
      dramatic increase in the rate of aggregation of Xenopus blastomeres, but does not
      enhance gap junction communication or induce axis duplication; hence, we argue
      that increased adhesion is not sufficient to account for beta-catenin's ability
      to regulate patterning or gap junction communication. We propose a signaling role
      for beta-catenin during axis formation in Xenopus.

PMID- 7589794
TI  - Effect on sperm-induced activation current and increase of cytosolic Ca2+ by
      agents that modify the mobilization of [Ca2+]i. I. Heparin and pentosan
      polysulfate.
AB  - The mechanism of the elevation of intracellular free Ca2+ ([Ca2+]i) induced by a
      single sperm in eggs of the sea urchin Lytechinus variegatus was investigated.
      Simultaneous measurements of [Ca2+]i, and of the activation current, were carried
      out on eggs microinjected with Ca Green-1 or Ca Green dextran, and voltage
      clamped at -20 mV. The microinjection of 0.5 to 1.0 mg/ml heparin (MW 6000) or
      pentosan polysulfate (MW 3000), final intracellular concentration, causes a
      concentration-dependent inhibition in all parameters of the sperm-induced
      elevation of [Ca2+]i and the phase 2 calcium-activated cation current (Ip). For
      each: (1) the onset is delayed; (2) the rate of change is slowed; and (3) the
      peak amplitude attained is diminished. In some experiments at the higher
      concentrations, the microinjected polysulfates cause the complete suppression of
      the sperm-induced elevation of [Ca2+]i and Ip. The entry of multiple sperm
      overcomes the inhibitory effects of the polysulfates. Our data suggest that
      inositol 1,4,5-trisphosphate is the primary mechanism responsible for the sperm
      induced release of Ca2+ from intracellular stores.

PMID- 7589795
TI  - Regional specification during embryogenesis in the inarticulate brachiopod
      Glottidia.
AB  - A fate map has been constructed for the lingulid brachiopod Glottidia pyramidata.
      The animal half of the egg forms part of the apical lobe and the dorsal valve of
      the larva. The vegetal half of the egg forms mesoderm and endoderm and is the
      site of gastrulation; it also forms part of the apical lobe and the ventral valve
      of the larva. The plane of the first cleavage goes through the animal-vegetal
      axis of the egg along the future plane of bilateral symmetry of the larva. The
      timing of regional specification in these embryos was examined by isolating
      animal or vegetal, anterior or posterior, or lateral regions at different times
      from prior to fertilization through gastrulation. Animal halves isolated at all
      stages formed an epithelial vesicle and did not gastrulate. When these halves
      were isolated from unfertilized eggs or early cleavage stage embryos, they
      usually did not form an apical lobe or valve; however, when the halves were
      isolated at later developmental stages, these structures differentiated in a high
      frequency of cases. Vegetal halves were isolated at all stages gastrulated and
      formed a larva; however, when these halves were isolated at gastrulation they
      frequently lacked a dorsal valve. When lateral cuts were made along the animal
      vegetal axis at all developmental stages, both halves gastrulated. When the cut
      was made perpendicular to the plane of the first cleavage from the four-cell
      stage on, one-half formed the anterior end and the other half formed the
      posterior end of the larva. These results suggest that there are localized
      determinants in the egg that specify the different regions of the larva, but
      there is also an inductive signal(s) from the vegetal region of the embryo that
      is necessary in order for cells that inherit a given determinant to
      differentiate. Embryogenesis in Glottidia is compared with articulate brachiopods
      and phoronids.

PMID- 7589793
TI  - Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell
      interaction in the mouse embryo.
AB  - The mouse Hedgehog gene family consists of three members, Sonic, Desert, and
      Indian hedgehog (Shh, Dhh, and Ihh, respectively), relatives of the Drosophila
      segment polarity gene, hedgehog (hh). All encode secreted proteins implicated in
      cell-cell interactions. One of these, Shh, is expressed in and mediates the
      signaling activities of several key organizing centers which regulate central
      nervous system, limb, and somite polarity. However, nothing is known of the roles
      of Dhh or Ihh, nor of the possible function of Shh during later embryogenesis. We
      have used serial-section in situ hybridization to obtain a detailed profile of
      mouse Hh gene expression from 11.5 to 16.5 days post coitum. Apart from the gut,
      which expresses both Shh and Ihh, there is no overlap in the various Hh
      expression domains. Shh is predominantly expressed in epithelia at numerous sites
      of epithelial-mesenchymal interactions, including the tooth, hair, whisker,
      rugae, gut, bladder, urethra, vas deferens, and lung, Dhh in Schwann and Sertoli
      cell precursors, and Ihh in gut and cartilage. Thus, it is likely that Hh
      signaling plays a central role in a diverse array of morphogenetic processes.
      Furthermore, we have compared Hh expression with that of a second family of
      signaling molecules, the Bone morphogenetic proteins (Bmps), vertebrate relatives
      of decapentaplegic, a target of the Drosophila Hh signaling pathway. The frequent
      expression of Bmp-2, -4, and -6 in similar or adjacent cell populations suggests
      a conserved role for Hh/Bmp interactions in vertebrate development.

PMID- 7589796
TI  - Synapse-associated expression of an acetylcholine receptor-inducing protein,
      ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing
      mammalian muscle.
AB  - Developing motor axons induce synaptic specializations in muscle fibers,
      including preferential transcription of acetylcholine receptor (AChR) subunit
      genes by subsynaptic nuclei. One candidate nerve-derived signaling molecule is
      AChR-inducing activity (ARIA)/heregulin, a ligand of the erbB family of receptor
      tyrosine kinases. Here, we asked whether ARIA and erbB kinases are expressed in
      patterns compatible with their proposed signaling roles. In developing muscle,
      ARIA was present not only at synaptic sites, but also in extrasynaptic regions of
      the muscle fiber. ARIA was synthesized, rather than merely taken up, by muscle
      cells, as indicated by the presence of ARIA mRNA in muscle and of ARIA protein in
      a clonal muscle cell line. ARIA-responsive myotubes expressed both erbB2 and
      erbB3, but little EGFR/erbB1 or erbB4. In adults, erbB2 and erbB3 were localized
      to the postsynaptic membrane. ErbB3 was restricted to the postsynaptic membrane
      perinatally, at a time when ARIA was still broadly distributed. Thus, our data
      are consistent with a model in which ARIA interacts with erbB kinases on the
      muscle cell surface to provide a local signal that induces synaptic expression of
      AChR genes. However, much of the ARIA is produced by muscle, not nerve, and the
      spatially restricted response may result from the localization of erbB kinases as
      well as of ARIA. Finally, we show that erbB3 is not concentrated at synaptic
      sites in mutant mice that lack rapsyn, a cytoskeletal protein required for AChR
      clustering, suggesting that pathways for synaptic AChR expression and clustering
      interact.

PMID- 7589797
TI  - Nerve cell differentiation in nerve-free tissue of epithelial hydra from
      precursor cells introduced by grafting. I. Tentacles and hypostome.
AB  - The differentiation of hydra nerve cells in the nerve-free tissue of epithelial
      hydra was examined in Hydra magnipapillata. Nerve cell precursors, the
      interstitial cells, were introduced into the upper half of epithelial hydra by
      grafting it onto the lower half of normal hydra. In the tentacles of grafted
      epithelial hydra, a small number of RF+ ganglion cells first appeared in the
      proximal area at 1.5 days after grafting, followed by the appearance of NV1+
      sensory cells in the same area about a day later. In the following days, both
      neuron types appeared more numerously in more distal positions. The front
      boundary for each type moved gradually from the base to the tip of the tentacles
      in about 7 days. In the hypostome, a small number of RF+ ganglion cells first
      appeared in the apex at 1.5 days. More nerve cells appeared in the following
      days, eventually forming a cluster of RF+ sensory cells at the apex surrounded by
      numerous RF+ ganglion cells in the adjacent tissue. These results show that nerve
      cells do not differentiate randomly in the epithelial hydra host. Instead,
      differentiation occurs in a strongly region-specific manner in the same way as in
      normal hydra, suggesting that epithelial cells in each region provide different
      cues or signals to produce region-specific nerve cell distribution in normal
      hydra tissue.

PMID- 7589798
TI  - Involvement of cyanide-resistant respiration in cell-type proportioning during
      Dictyostelium development.
AB  - Involvement of cyanide (CN)-resistant respiration in cell-type proportioning was
      analyzed using the developmental system of Dictyostelium discoideum. When
      migrating slugs were vitally stained with rhodamine 123, which is known to stain
      actively respirating mitochondria coupled with an elevated electronic potential
      of the inner membrane, the posterior prespore region was stained more strongly
      than the anterior prestalk region. Application of benzohydroxamic acid (BHAM) and
      propyl gallate, specific inhibitors of CN-resistant respiration, to starved
      Dictyostelium cells induced formation of unique cell masses, in which almost all
      of the cells differentiated into stalk-like cells with a large vacuole and thick
      cell wall. BHAM was also found to enhance the expressions of prestalk-specific
      genes such as ecmA and ecmB in the unique cell mass in a position-dependent
      manner. In contrast, the expression of a prespore-specific gene, Dp87, was almost
      completely inhibited by BHAM. Taken together these results strongly suggest the
      involvement of CN-resistant respiration in the proportion regulation of cell
      types differentiating during the Dictyostelium development.

PMID- 7589799
TI  - Activin and its receptors during gastrulation and the later phases of mesoderm
      development in the chick embryo.
AB  - We have cloned chick homologues of the type-II activin receptor, which we have
      designated cActR-IIA and -IIB. Binding assays show that the two receptors are
      indistinguishable in their ability to bind activin-A, with comparable kds.
      Injection of mRNAs encoding these receptors into Xenopus embryos causes axial
      duplications. Expression of both receptors can first be detected in the primitive
      streak by in situ hybridization. This suggests that these genes may be activated
      in response to mesoderm induction. In agreement with this, we find that treatment
      of preprimitive streak chick embryos with activin-A leads to rapid induction of
      the expression of cActR-IIB. At later stages, cActR-IIA transcripts become
      localized mainly in the notochord and myotome and cActR-IIB in the dorsal neural
      tube, proximal-anterior part of the limb bud, sensory placodes, and specific
      regions of the fore- and midbrain. To test the response of early chick embryonic
      tissues to activin, we designed a new in vitro assay for differentiation. We find
      that explants of area opaca epiblast or posterior primitive streak from various
      stages can respond to activin treatment by differentiating into a variety of
      mesodermal cell types in a dose-dependent manner. These results suggest that the
      importance of activin-related signaling pathways is not confined to
      pregastrulation stages and that these receptors may be involved in mediating the
      effects of inducing signals during later stages of development of the mesoderm,
      limbs, and nervous system.

PMID- 7589800
TI  - Regulation of muscle differentiation by the MEF2 family of MADS box transcription
      factors.

PMID- 7589802
TI  - Neoplastic transformation and aberrant cell-cell interactions in genetic mosaics
      of lethal(2)giant larvae (lgl), a tumor suppressor gene of Drosophila.
AB  - Homozygosity for lethal(2)giant larvae (lgl), a mutation in a tumor suppressor
      gene of Drosophila, induces neoplasia of the imaginal discs. To explore the
      developmental capacities of lgl mutant cells, we have investigated their growth
      and differentiation in genetic mosaics. Adult wings mosaic for lgl displayed
      abnormal growth and differentiation of the lgl mutant and neighboring wild-type
      cells, suggesting aberrant cell-cell interactions during development. lgl mutant
      clones also straddled the anteroposterior boundary of the wing imaginal disc,
      apparently due to failure of the cells of the anterior and the posterior
      compartment to segregate at the boundary. To further test if anteroposterior
      compartmentalization takes place in the neoplastic imaginal discs of lgl mutant
      larvae, we studied the expression of an engrailed (en)-specific lacZ reporter
      gene during progressive stages of their tumorous growth. Our results show that en
      is activated in the posterior compartments of the neoplastic imaginal discs.
      However, during later stages of tumorous overgrowth, the en-expressing and
      nonexpressing cells appear to show extensive intermixing. These observations
      suggest that neoplastic transformation of imaginal discs involves loss of their
      normal cell-cell interactions and signaling.

PMID- 7589801
TI  - Is there a Brachyury the Second? Analysis of a transgenic mutation involved in
      notochord maintenance in mice.
AB  - A new phenotype mapping to the t-complex, which is designated Brachyury the
      Second (T2), is characterized by a slightly shortened tail in heterozygotes and
      homozygous failure to form an organized notochord with subsequent abnormal
      development of posterior somites and neural tube. The phenotype of T2
      superficially resembles that of Brachyury; however, there are several important
      differences. Brachyury homozygotes fail to make posterior somites, notochord,
      floor plate, and a placental connection, resulting in death by 10.5 days of
      development. In contrast, T2 homozygotes make posterior somites, scattered
      notochord cells, and floorplate and achieve an allantoic connection. However,
      despite making a maternal connection, T2 homozygotes cease development at E11.5
      and die soon after. We have cloned and analyzed the transgene insertion site,
      which maps within 100 kb of the Brachyury gene, but does not seem to physically
      interrupt nor affect transcription from that locus. The existence of a second
      gene mapping near Brachyury and affecting the same developmental processes was
      alluded to over 50 years ago and has been debated ever since. An embryological
      description of T2 is presented, as is a discussion of the implications of a
      single, larger Brachyury locus versus two closely linked genes coordinately
      regulating axial development.

PMID- 7589803
TI  - Two cis elements collaborate to spatially repress transcription from a sea urchin
      promoter.
AB  - The expression pattern of many territory-specific genes in metazoan embryos is
      maintained by an active process of negative spatial regulation. However, the
      mechanism of this strategy of gene regulation is not well understood in any
      system. Here we show that reporter constructs containing regulatory sequence for
      the SM30-alpha gene of Stronglyocentrotus purpuratus are expressed in a pattern
      congruent with that of the endogenous SM30 gene(s), largely as a result of active
      transcriptional repression in cell lineages in which the gene is not normally
      expressed. Chloramphenicol acetyl transferase assays of deletion constructs from
      the 2600-bp upstream region showed that repressive elements were present in the
      region from -1628 to -300. In situ hybridization analysis showed that the spatial
      fidelity of expression was severely compromised when the region from -1628 to 
      300 was deleted. Two highly repetitive sequence motifs, (G/A/C)CCCCT and
      (T/C)(T/A/C)CTTTT(T/A/C), are present in the -1628 to -300 region.
      Representatives of these elements were analyzed by gel mobility shift experiments
      and were found to interact specifically with protein in crude nuclear extracts.
      When oligonucleotides containing either sequence element were co-injected with a
      correctly regulated reporter as potential competitors, the reporter was expressed
      in inappropriate cells. When composite oligonucleotides, containing both sequence
      elements, were fused to a misregulated reporter, the expression of the reporter
      in inappropriate cells was suppressed. Comparison of composite oligonucleotides
      with oligonucleotides containing single constituent elements show that both
      sequence elements are required for effective spatial regulation. Thus, both
      individual elements are required, but only a composite element containing both
      elements is sufficient to function as a tissue-specific repressive element.

PMID- 7589806
TI  - Developmental regulation of genomic imprinting during gametogenesis.
AB  - Successful mammalian development requires both the male and female genomes. This
      is due in part to genomic imprinting, which results in offspring inheriting only
      one functional copy of a gene from either the mother or the father. Evidence
      suggests that this specialization of the parental genomes is established during
      gametogenesis when the imprint pattern inherited from the parent is switched to
      reflect the sex of the progeny. We used reverse transcription-PCR to analyze the
      allele-specific expression of Igf-2, Igf-2r, and H19 in the testes and ovaries of
      mice derived from an interspecies cross between Mus musculus and Mus spretus.
      Because of genomic imprinting, Igf-2 is expressed only from the paternal allele
      and Igf-2r and H19 only from the maternal allele, in most tissues. Although
      allele-specific expression was maintained in the neonatal testis and ovary,
      relaxation of imprinting was detected by 7 days after birth in the male and
      continued during testis development. In the female, relaxation of the Igf-2 and
      Igf-2r parental imprints was observed in the adult ovary and oocyte. These
      results (1) indicate that imprinted expression is relaxed during gametogenesis,
      presumably as a consequence or prerequisite of the imprinting mechanism, and (2)
      predict a subsequent imprinting event after which the allele-specific expression
      of Igf-2, Igf-2r, and H19 reflects the parent of origin.

PMID- 7589804
TI  - BMP-4 regulates the dorsal-ventral differences in FGF/MAPKK-mediated mesoderm
      induction in Xenopus.
AB  - Recent studies on Xenopus development have revealed an increasingly complex array
      of inductive, prepatterning, and competence signals that are necessary for proper
      mesoderm formation. In this study, we establish that fibroblast growth factor
      (FGF) signals through mitogen-activated protein kinase kinase (MAPKK) to induce
      mesodermal gene expression. We demonstrate that a partially activated form of
      MAPKK restores expression of the mesodermal genes Xcad-3 and Xbra, eliminated by
      the dominant-negative FGF receptor (delta FGFR). Similar to the results reported
      earlier with delta FGFR, expression of a dominant-negative form of MAPKK (MAPKKD)
      preferentially eliminates the dorsal expression of Xcad-3 and Xbra. We tested
      whether the regional localization of bone morphogenetic protein-4 (BMP-4) could
      explain why both MAPKKD and delta FGFR eliminate the dorsal and not the ventral
      expression of Xcad-3 and Xbra. We show that ectopic expression of BMP-4 is
      sufficient to maintain the dorsal expression of Xcad-3 and Xbra in embryos
      containing delta FGFR and that expression of a dominant-negative BMP receptor
      reduces the dorsal-ventral differences in delta FGFR embryos. These results
      indicate that regional localization of BMP-4 is responsible for the dorsal
      ventral asymmetry in FGF/MAPKK-mediated mesoderm induction.

PMID- 7589805
TI  - Developmental analysis of the Hba(th-J) mouse mutation: effects on mouse peri
      implantation development and identification of two candidate genes.
AB  - The Hba(th-J) mouse mutation is a deletion on chromosome 11 that spans the alpha
      globin complex and causes alpha-thalassemia in heterozygous animals and in utero
      death of embryos homozygous for the deletion. We hypothesised that one or more
      genes closely linked to the Hba locus are also deleted in these mutant mice and
      that deletion of these additional genes is responsible for the embryo lethality.
      We have analysed the developmental profile of mutant embryos using a PCR assay to
      distinguish homozygous embryos from wild-type and heterozygous embryos. No
      homozygous embryos are detectable on Day 6.5 of gestation and morphological
      analysis of embryos on Day 5.5 shows that both the embryonic and extraembryonic
      ectoderm of the egg cylinder are reduced in size and contain degenerate cells.
      Preimplantation homozygous embryos are morphologically normal with the same
      proportion developing to the blastocyst stage as control embryos. However, the
      cell number of homozygous embryos on Day 4.5 is significantly reduced due
      predominantly to a decrease in the cell number of the trophectoderm and not the
      inner cell mass. When homozygous blastocysts are plated in vitro, outgrowth of
      giant trophectoderm cells appears similar to that of wild-type embryos but
      outgrowth of the inner cell mass is affected. Cells from the inner cell mass of
      homozygous embryos appear to undergo necrosis and dissociate from the
      trophectoderm outgrowth after 3 to 4 days in culture. These studies demonstrate
      that the development of both the inner cell mass and the trophectoderm of embryos
      homozygous for the Hbath-J deletion is affected by the mutation. We have used
      quantitative Southern blotting to show that 3-methyladenine glycosylase (mpg) and
      dist1, two genes closely linked to the Hba locus on chromosome 11, are also
      deleted in this mutation. Reverse transcriptase-polymerase chain reaction
      analyses demonstrate that mpg and dist1 are normally expressed by preimplantation
      and early postimplantation embryos, whereas alpha-globin transcripts from the Hba
      locus are not detected until Day 7.5 of gestation. These studies demonstrate that
      deletion of the mpg or dist1 genes is likely to be responsible for the homozygote
      embryo lethality and the potential roles of these gene products in early
      embryogenesis are discussed.

PMID- 7589807
TI  - Regulated processing of dec-1 eggshell proteins in Drosophila.
AB  - The Drosophila dec-1 gene encodes multiple products that are necessary for proper
      eggshell assembly. During stages 9-12 of oogenesis the ovarian follicle cells
      synthesize three alternatively spliced dec-1 RNAs that encode proteins of 106,
      125, and 177 kDa. All three of these primary translation products undergo
      developmentally regulated posttranslational cleavages. Antibodies to trpE fusion
      proteins containing different regions of the dec-1 proteins have been used to
      identify processing intermediates as well as stable derivatives of fc106, fc125,
      and fc177. fc106, the most abundant product of the locus, is cleaved at its N
      terminus, producing an N-terminal 25-kDa derivative and s80, a stage 10 eggshell
      protein. During late oogenesis N-terminal cleavage of s80 yields a 20-kDa N
      terminal derivative and a 60-kDa eggshell protein. fc125, which differs from
      fc106 by a C-terminal extension, is processed at its N-terminus through a series
      of transient intermediates to a stable 95-kDa C-terminal derivative in late stage
      10 egg chambers. Unlike its s80 counterpart, the 95-kDa derivative is not
      subjected to later cleavage events. fc177, synthesized during stages 11-12, is
      cleaved to a stable C-terminal derivative of approximately 85 kDa. Although all
      of the cleavage sites fall within regions that are common to fc106, fc125, and
      fc177, each protein follows a different maturation pathway which results in a
      variety of proteins with distinctive N- and C-termini. Our data suggest that
      inter- or intramolecular interactions dictated by the C-terminal ends of the
      molecules determine the pathway followed by each dec-1 protein.

PMID- 7589808
TI  - Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis.
AB  - Transcription factors belonging to the basic helix-loop-helix (bHLH) family have
      been shown to control differentiation of a variety of cell types. Tissue-specific
      bHLH proteins dimerize preferentially with ubiquitous bHLH proteins to form
      heterodimers that bind the E-box consensus sequence (CANNTG) in the control
      regions of target genes. Using the yeast two-hybrid system to screen for tissue
      specific bHLH proteins, which dimerize with the ubiquitous bHLH protein E12, we
      cloned a novel bHLH protein, named Dermo-1. Within its bHLH region, Dermo-1
      shares extensive homology with members of the twist family of bHLH proteins,
      which are expressed in embryonic mesoderm. During mouse embryogenesis, Dermo-1
      showed an expression pattern similar to, but distinct from, that of mouse twist.
      Dermo-1 was expressed at a low level in the sclerotome and dermatome of the
      somites, and in the limb buds at Day 10.5 post coitum (p.c.), and accumulated
      predominantly in the dermatome, prevertebrae, and the derivatives of the
      branchial arches by Day 13.5 p.c. As differentiation of prechondrial cells
      proceeded, Dermo-1 expression became restricted to the perichondrium. Expression
      of Dermo-1 increased continuously in the dermis through Day 17.5 p.c. and was
      also detected in the dermis of neonates, but became downregulated in adult
      tissues. The Dermo-1 protein bound the E-box consensus sequence in the presence
      of E12, but transcriptional activity was not detectable. Instead, Dermo-1
      repressed transcriptional activity of myogenic bHLH proteins. The expression
      pattern of Dermo-1 suggests that it functions as a regulator of gene expression
      in a subset of mesenchymal cell lineages including developing dermis.

PMID- 7589810
TI  - Apoptosis in the neuronal lineage of the mouse olfactory epithelium: regulation
      in vivo and in vitro.
AB  - The olfactory epithelium (OE) of the mouse provides a unique system for
      understanding how cell birth and cell death interact to regulate neuron number
      during development and regeneration. We have examined cell death in the OE in
      normal adult mice; in adult mice subjected to unilateral olfactory bulbectomy
      (surgical removal of one olfactory bulb, the synaptic target of olfactory
      receptor neurons (ORNs) of the OE); and in primary cell cultures derived from
      embryonic mouse OE. In vivo, cells at all stages in the neuronal lineage-
      proliferating neuronal precursors, immature ORNs, and mature ORNs--displayed
      signs of apoptotic cell death; nonneuronal cells did not. Bulbectomy dramatically
      increased the number of apoptotic cells in the OE on the bulbectomized side.
      Shortly following bulbectomy, increased cell death involved neuronal cells of all
      stages. Later, cell death remained persistently elevated, but this was due to
      increased apoptosis by mature ORNs alone. In vitro, apoptotic death of both ORNs
      and their precursors could be inhibited by agents that prevent apoptosis in other
      cells: aurintricarboxylic acid (ATA), a membrane-permeant anlog of cyclic AMP
      (CPT-cAMP), and certain members of the neurotrophin family of growth factors
      (brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 5), although
      no neurotrophin was as effective at promoting survival as ATA or CPT-cAMP.
      Consistent with observed effects of neurotrophins, immunohistochemistry localized
      the neurotrophin receptors trkB and trkC to fractions of ORNs scattered
      throughout neonatal OE. These results suggest that apoptosis may regulate
      neuronal number in the OE at multiple stages in the neuronal lineage and that
      multiple factors-potentially including certain neurotrophins--may be involved in
      this process.

PMID- 7589809
TI  - Progression and recapitulation of the chondrocyte differentiation program:
      cartilage matrix protein is a marker for cartilage maturation.
AB  - During endochondral bone formation, chondrocytes in the cartilaginous anlage of
      long bones progress through a spatially and temporally regulated differentiation
      program before being replaced by bone. To understand this process, we have
      characterized the differentiation program and analyzed the relationship between
      chondrocytes and their extracellular environment in the regulation of the
      program. Our results indicate that, within an epiphyseal growth plate, the zone
      of proliferating chondrocytes is not contiguous with the zone of hypertrophic
      chondrocytes identified by the transcription of the type X collagen gene. We find
      that the postproliferative chondrocytes which make up the zone between the zones
      of proliferation and hypertrophy specifically transcribe the gene for cartilage
      matrix protein (CMP). This zone has been termed the zone of maturation. The
      identification of this unique population of chondrocytes demonstrates that the
      chondrocyte differentiation program consists of at least three stages. CMP
      translation products are present in the matrix surrounding the nonproliferative
      chondrocytes of both the zones of maturation and hypertrophy. Thus, CMP is a
      marker for postmitotic chondrocytes. As a result of the changes in gene
      expression during the differentiation program, chondrocytes in each zone reside
      in an extracellular matrix with a unique macromolecular composition. Chondrocytes
      in primary cell culture can proceed through the same differentiation program as
      they do in the cartilaginous rudiments. In culture, a wave of differentiation
      begins in the center of a colony and spreads to its periphery. The cessation of
      proliferation coincides with the appearance of CMP and eventually the cells
      undergo hypertrophy and synthesize type X collagen. These results reveal distinct
      switches at the proliferative-maturation transition and at the maturation
      hypertrophy transition during chondrocyte differentiation and indicate that
      chondrocytes synthesize new matrix molecules and thus modify their preexisting
      microenvironment as differentiation progresses. However, when "terminally"
      differentiated hypertrophic chondrocytes are released from their surrounding
      environment and incubated in pellet culture, they stop type X collagen synthesis,
      resume proliferation, and reinitiate aggrecan synthesis. Eventually they cease
      proliferation and reinitiate CMP synthesis and finally type X collagen. Thus they
      are capable of recapitulating all three stages of the differentiation program in
      vitro. The data suggest a high degree of plasticity in the chondrocyte
      differentiation program and demonstrate that the progression and maintenance of
      this program is regulated, at least in part, by the extracellular environment
      which surrounds a differentiating chondrocyte during endochondral bone formation.

PMID- 7589811
TI  - Genetic analysis of developmental mechanisms in Hydra. XXII. Two types of female
      germ stem cells are present in a male strain of Hydra magnipapillata.
AB  - Three types of interstitial stem cell subpopulation were isolated from Hydra
      magnipapillata, and their roles in sex determination were examined. A
      subpopulation of interstitial stem cells restricted to the sperm differentiation
      pathway was isolated previously from strain nem-1 (male). Another subpopulation
      restricted to the egg differentiation pathway was also isolated from the same
      strain. Hydroxyurea treatment was used for isolation in both cases.
      "Pseudoepithelial hydra" containing only sperm- or egg-restricted stem cell but
      no other interstitial stem cell types were maintained by force-feeding for 2
      years. Sex reversal from egg- to sperm-restricted stem cells occurred three times
      during this period. Both of these two stem cell types are numerous in the central
      gastric region of the pseudoepithelial hydra, but absent in the foot region below
      the budding zone. Foot tissue was cut out from normal nem-1 polyps (male) and
      allowed to regenerate. The regenerates produced eggs but no sperm upon sex
      induction. These and other results suggest that the foot tissue contains
      multipotent stem cells capable of differentiating into eggs during sexual
      differentiation. These observations suggest that strain nem-1 (male) contains
      three types of interstitial stem cell subpopulations: (1) sperm-restricted stem
      cells, (2) egg-restricted stem cells, and (3) multipotent stem cells capable of
      differentiating into nerve cells, nematocytes, and eggs. Upon sex induction,
      however, differentiation of eggs by the latter two types is suppressed, and only
      sperm are produced by the sperm-restricted stem cells. Evidence is presented
      which suggests that similar "phenotypic males," which normally only produce sperm
      but contain the stem cell types capable of differentiating into eggs, occur
      widely in Hydra magnipapillata. A possible relationship between phenotypic male
      hydra and hermaphroditic hydra is discussed.

PMID- 7589812
TI  - Specification of the anteroposterior neural axis through synergistic interaction
      of the Wnt signaling cascade with noggin and follistatin.
AB  - Embryological data and the activities of the neural-inducing factors noggin and
      follistatin are consistent with the hypothesis that the nervous system is
      initially induced with an anterior character, with subsequent signals imparting
      posterior pattern. We report that Xwnt3a is a candidate for involvement in
      anteroposterior neural patterning, as it synergizes with the neural-inducing
      factors noggin and follistatin to increase the expression of posterior neural
      genes. Furthermore we show that beta-catenin, an intracellular protein implicated
      in the Wnt signal transduction cascade, mimics the activity of Xwnt3a. These data
      suggest that the generation of pattern within the vertebrate nervous system may
      rely on synergism between a Wnt signaling pathway and multiple neural-inducing
      factors.

PMID- 7589814
TI  - Characterization of myosin-IA and myosin-IB, two unconventional myosins
      associated with the Drosophila brush border cytoskeleton.
AB  - The expression patterns of myosin-IA (MIA) and myosin-IB (MIB), two novel
      unconventional myosins from Drosophila melanogaster, have been characterized
      through immunoblot analysis and immunocytochemistry of embryos, larvae, and
      adults. The appearance and distribution of both proteins during embryogenesis is
      correlated with the formation of a brush border within the alimentary canal as
      documented at the ultrastructural level. MIA and MIB, both found predominantly at
      the basolateral domain of immature enterocytes, exhibit increased expression at
      the apical domain of differentiated enterocytes co-incident with microvillus
      assembly. Colocalization of MIA and MIB to larval and adult gut by confocal
      microscopy demonstrates distinct but overlapping subcellular distributions of
      these two proteins. In the larval brush border, MIA is enriched in the subapical
      terminal web domain whereas MIB is found predominantly in the apical microvillar
      domain. In the adult gut, MIA and MIB both exhibit a microvillar component as MIA
      attains a more apical position in addition to its previous terminal web locale.
      MIB is also found in egg chambers at both the basolateral and apical surfaces of
      the somatic follicle cells during oogenesis. MIA and MIB both demonstrate ATP
      dependent extraction from the larval brush border cytoskeleton and exogenous F
      actin, biochemical properties characteristic of functional myosins-I.

PMID- 7589813
TI  - Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse
      embryogenesis.
AB  - The four myogenic basic helix-loop-helix proteins, MyoD, myogenin, Myf-5, and
      MRF4, can each activate skeletal muscle differentiation when introduced into
      nonmuscle cells. During embryogenesis, each of these genes is expressed in a
      unique but overlapping pattern in skeletal muscle precursors and their
      descendants. Gene knockout experiments have shown that MyoD and Myf-5 play
      seemingly redundant roles in the generation of myoblasts. However, the role of
      either of these genes during differentiation in vivo has not been determined. In
      contrast, a myogenin-null mutation blocks differentiation and results in a
      dramatic decrease in muscle fiber formation, yet the role of myogenin in the
      generation or maintenance of myoblast populations is not known. Because myogenin
      possesses the same myogenic activity as MyoD and Myf-5 in vitro and the
      expression patterns of these three genes overlap in vivo, we sought to determine
      if myogenin shares certain functions with either MyoD or Myf-5 in vivo. We
      therefore generated mice with double homozygous null mutations in the genes
      encoding MyoD and myogenin or Myf-5 and myogenin. These mice showed embryonic and
      perinatal phenotypes characteristic of the combined defects observed in mice
      mutant for each gene alone. As shown by histological analysis and expression of
      muscle-specific genes, the numbers of undifferentiated myoblasts and residual
      myofibers were comparable between myogenin-mutant homozygotes and the double
      mutant homozygotes. Myoblasts isolated from neonates of the combined mutant
      genotypes underwent myogenesis in tissue culture, indicating that no more than
      two of the four myogenic factors are required to support muscle differentiation.
      These results demonstrate that the functions of myogenin do not overlap with
      those of MyoD or Myf-5 and support the view that myogenin acts in a genetic
      pathway downstream of MyoD and Myf-5.

PMID- 7589815
TI  - Differential regulation of oocyte maturation and cumulus expansion in the mouse
      oocyte-cumulus cell complex by site-selective analogs of cyclic adenosine
      monophosphate.
AB  - In the present study, we have examined how differential distribution of cyclic
      adenosine 5'-monophosphate (cAMP)-dependent protein kinase isozymes within the
      mouse oocyte-cumulus cell complex might influence the physiological response of
      the complex to cAMP, by determining the actions of site-selective cAMP analogs on
      oocyte maturation and cumulus expansion. Five different analogs of cAMP were
      utilized: 8-thiomethyl-cAMP and 8-bromo-cAMP, which bind to site 1 on the type II
      regulatory subunit (RII) of cAMP-dependent protein kinase A (PKA); 8
      aminohexylamino-cAMP, which binds to site 1 on the type I regulatory subunit (RI)
      of PKA; N6-monobutyryl cAMP, which binds to site 2 on either RI or RII; and 8
      piperidino-cAMP, which binds to either site 1 on RII or site 2 on RI. These
      analogs were tested alone or in paired combinations that synergistically activate
      either the type I or type II PKA isozyme. When tested alone, analogs that can
      bind to, and presumably activate, type I PKA were the most potent inhibitors of
      germinal vesicle breakdown (GVB) in both cumulus cell-enclosed and denuded
      oocytes. Consistent with this result was the finding that paired combinations of
      analogs that selectively activate type I PKA were also most effective in
      preventing GVB. On the other hand, pulsing meiotically arrested cumulus cell
      enclosed oocytes with high concentrations of analogs that bind to PKA II, or with
      paired combinations of analogs that selectively activate type II PKA, led to
      induction of GVB; stimulation with analogs or combinations thereof that
      presumably stimulate type I PKA was less effective. Cumulus expansion in response
      to PKA stimulation showed similar selectivity in that type II PKA-stimulating
      treatments were considerably more effective in provoking expansion than type I
      PKA-stimulating treatments. 8-N3-[32P]cAMP photoaffinity labeling of PKA
      regulatory subunits revealed that only RI was present in oocyte extracts, while
      extracts from oocyte-cumulus cell complexes contained both RI and RII. These
      results support the hypothesis that type II PKA mediates cAMP-stimulated cumulus
      expansion and resumption of meiotic maturation, while direct elevation of type I
      PKA within the oocyte is instrumental in maintaining meiotic arrest.

PMID- 7589816
TI  - Expression of snail2, a second member of the zebrafish snail family, in cephalic
      mesendoderm and presumptive neural crest of wild-type and spadetail mutant
      embryos.
AB  - Transcripts of a newly discovered gene called snail2, encoding a zinc finger
      protein of the Snail family, first appear in rows of cephalic mesendodermal cells
      in gastrulating zebrafish embryos. At the end of gastrulation, snail2 RNA
      accumulates in a domain of ectodermal cells that mark the border between the
      epidermal epithelium and the neural plate and includes precursors of the neural
      crest. During somitogenesis, snail2 expression becomes restricted to neural
      crest. snail2 is thus one of the earliest genes yet known to be specifically
      expressed in neural crest in zebrafish embryos. Since snail2 is expressed in
      mesendoderm, a tissue layer whose convergence in the trunk is known to be altered
      in embryos homozygous for the spadetail mutation, we examined snail2 expression
      in spadetail embryos. In these mutants, the number of cephalic mesendodermal
      cells expressing snail2 is strongly reduced and the distribution of cells
      containing snail2 and no tail transcripts in the axial mesoderm is much broader
      than normal Moreover, the embryos are shorter than normal at the end of
      gastrulation. This shows that, in addition to the failure of paraxial mesoderm to
      converge normally in the trunk during gastrulation, spadetail also affects the
      elongation of the embryo and the convergence of axial and lateral mesendoderm in
      both trunk and head.

PMID- 7589817
TI  - Ontogeny of eyeblink conditioning in the rat: auditory frequency and
      discrimination learning effects.
AB  - The present study sought to determine whether acoustic properties of the auditory
      conditioned stimulus (CS) or the use of a discrimination learning procedure would
      alter the emergence of eyeblink conditioning between postnatal Days 17 and 24
      (Days 17-24) in the rat. In Experiment 1, we employed a 3 x 2 x 2 factorial
      design, involving pitch of the auditory CS (2.8, 5.0, and 9.0 kHz), training
      condition (paired vs. unpaired), and age (Days 17 or 24). Associative learning
      was evident at all tone frequencies on Day 24, but increased across frequencies
      on Day 17, although large age differences in conditioning remained at all tone
      frequencies. In Experiment 2, rat pups were trained to discriminate 2.8 versus
      9.0-kHz tones on Day 17 or Day 24. Eyeblink conditioning increased with tone
      frequency on Day 24 but discriminative conditioning failed to appear on Day 17.
      These findings are discussed in relation to the role of auditory system
      maturation in the ontogeny of eyeblink conditioning.

PMID- 7589818
TI  - Prenatal stress alters immune function in the offspring of rats.
AB  - Pregnant rats were either exposed to restraint under bright lights for 45 min
      three times daily (n = 7) or were left undisturbed (n = 8) during Days 14-21 of
      gestation. Offspring were tested for cellular immune responses as measured by
      Concanavalin A-stimulated proliferation and Natural Killer (NK) cytotoxicity of
      splenocytes as juveniles or adults, or were tested for specific humoral immune
      responses to in vivo challenge with the antigen Keyhole Limpet Hemocyanin (KLH)
      as adults. Results indicated that: (a) Proliferation did not vary as a function
      of sex or prenatal treatment in either juvenile or adult offspring; (b) in
      juveniles NK cytotoxicity was marginally lower in males as compared to females,
      and was also marginally reduced by prenatal stress in males but not females,
      whereas in adults, NK cytotoxicity was marginally enhanced by prenatal stress in
      both sexes; and (c) prenatally stressed offspring of both sexes had higher levels
      of anti-KLH antibodies as compared to controls.

PMID- 7589819
TI  - The surface evoked potential and parvalbumin-immunoreactivity in the
      somatosensory cortex of the developing rat.
AB  - The development of the rat somatosensory system was followed
      electrophysiologically and immunohistochemically. In the surface evoked potential
      elicited in the primary somatosensory cortex by electrical stimulation of the
      whisker C3 follicle, a short-latency positive wave was first recorded on
      postnatal Day 2. A long-latency positive wave was recorded in some pups on
      postnatal Day 7 and in most pups on postnatal Day 8. On postnatal Day 10, a P/N
      complex appeared between the short- and long-latency positive waves. Parvalbumin,
      believed to appear with functional maturation, appeared mainly after postnatal
      Day 7 in Layer V in the underlying area, although a few weakly stained cells
      appeared on postnatal Day 5. On postnatal Day 10, weakly stained cells appeared
      in the area containing barrels; their staining increased with time. In this
      system, electrophysiological and immunohistochemical parameters changed by the
      3rd postnatal week with the most marked changes occurring within 2 postnatal
      weeks.

PMID- 7589820
TI  - U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II
      diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.
AB  - The objective of the U.K. Prospective Diabetes Study is to determine whether
      improved blood glucose control in type II diabetes will prevent the complications
      of diabetes and whether any specific therapy is advantageous or disadvantageous.
      The study will report in 1998, when the median duration from randomization will
      be 11 years. This report is on the efficacy of therapy over 6 years of follow-up
      and the overall incidence of diabetic complications. Subjects comprised 4,209
      newly diagnosed type II diabetic patients who after 3 months' diet were
      asymptomatic and had fasting plasma glucose (FPG) 6.0-15.0 mmol/l. The study
      consists of a randomized controlled trial with two main comparisons: 1) 3,867
      patients with 1,138 allocated to conventional therapy, primarily with diet, and
      2,729 allocated to intensive therapy with additional sulfonylurea or insulin,
      which increase insulin supply, aiming for FPG < 6 mmol/l; and 2) 753 obese
      patients with 411 allocated to conventional therapy and 342 allocated to
      intensive therapy with metformin, which enhances insulin sensitivity. In the
      first comparison, in 2,287 subjects studied for 6 years, intensive therapy with
      sulfonylurea and insulin similarly improved glucose control compared with
      conventional therapy, with median FPG at 1 year of 6.8 and 8.2 mmol/l,
      respectively (P < 0.0001). and median HbA1c of 6.1 and 6.8%, respectively (P <
      0.0001). During the next 5 years, the FPG increased progressively on all
      therapies (P < 0.0001) with medians at 6 years in the conventional and intensive
      groups, FPG 9.5 and 7.8 mmol/l, and HbA1c 8.0 and 7.1%, respectively. The
      glycemic deterioration was associated with progressive loss of beta-cell
      function. In the second comparison, in 548 obese subjects studied for 6 years,
      metformin improved glucose control similarly to intensive therapy with
      sulfonylurea or insulin. Metformin did not increase body weight or increase the
      incidence of hypoglycemia to the same extent as therapy with sulfonylurea or
      insulin. A high incidence of clinical complications occurred by 6-year follow-up.
      Of all subjects, 18.0% had suffered one or more diabetes-related clinical
      endpoints, with 12.1% having a macrovascular and 5.7% a microvascular endpoint.
      Sulfonylurea, metformin, and insulin therapies were similarly effective in
      improving glucose control compared with a policy of diet therapy. The study is
      examining whether the continued improved glucose control, obtained by intensive
      therapy compared with conventional therapy (median over 6 years HbA1c 6.6%
      compared with 7.4%), will be clinically advantageous in maintaining health.

PMID- 7589822
TI  - Characterization of insulin resistance and NIDDM in transgenic mice with reduced
      brown fat.
AB  - We recently created a new model of murine obesity through transgenic ablation of
      brown adipose tissue (BAT) using a tissue-specific toxigene (6). The goal of the
      present study was to further define the altered glucose homeostasis and insulin
      resistance in these transgenic animals. Despite an approximately 30% increase in
      total body lipid, no abnormalities were observed in 6-week-old transgenic
      animals. At the age of 22-26 weeks, marked obesity in transgenic mice was
      associated with significant increases in blood glucose and plasma insulin levels
      and an abnormal response to both intraperitoneal glucose and insulin tolerance
      tests. Glucose transport in soleus muscle was reduced, with the response to
      insulin stimulation blunted by up to 85% in males and 55% in females. The total
      number of insulin receptors was decreased by 36% in muscle and 59% in adipose
      tissue of transgenic animals. Insulin receptor tyrosine kinase activity, which
      was assessed following maximal insulin stimulation in vivo, was reduced in
      transgenic animals by 59% in muscle and 56% in fat. GLUT4 mRNA and protein was
      unchanged in muscle of transgenic animals compared with in that of controls but
      was significantly reduced in adipose tissue. In conclusion, primary BAT
      deficiency results in the development of glucose intolerance or diabetes and
      severe insulin resistance with both receptor and postreceptor components. These
      animals should be a useful model for studies of obesity-linked diabetes and
      insulin resistance and related complications.

PMID- 7589823
TI  - Hypoglycemic effects of peroxovanadium compounds in Sprague-Dawley and diabetic
      BB rats.
AB  - Highly purified peroxovanadium (pV) compounds, each containing an oxo ligand, one
      or two peroxo anions, and an ancillary ligand in the inner coordination sphere of
      vanadium, were shown to decrease plasma glucose markedly in both normal Sprague
      Dawley and insulin-deprived diabetic BB rats. Maximal decreases in plasma glucose
      were at 60-100 min after intravenous, intraperitoneal, or subcutaneous
      administration. Synergism between these compounds and insulin was observed.
      Whereas parenterally administered orthovanadate or vanadyl sulfate did not induce
      hypoglycemia before inducing acute mortality, pV compounds effected hypoglycemia
      at doses much lower than those inducing acute mortality. When administered
      subcutaneously over a period of 3 days to insulin-deprived diabetic BB rats, pV
      compounds, but not vanadate, caused a significant decrease in plasma glucose
      concentrations and prevented the appearance of ketosis in these animals. Thus, pV
      compounds are the first agents other than insulin that acutely and markedly
      reduce plasma glucose in hypoinsulinemic diabetic BB rats.

PMID- 7589821
TI  - Linkage analysis of 19 candidate regions for insulin resistance in familial
      NIDDM.
AB  - As part of an ongoing search for diabetes susceptibility loci, we tested linkage
      with non-insulin-dependent diabetes mellitus (NIDDM) for 19 candidate loci or
      regions chosen for their potential to affect directly or indirectly the action of
      insulin. Loci were associated with insulin resistance, known effects on lipid
      metabolism, or effects on glucose metabolism or insulin action. Loci included the
      insulin-responsive (GLUT4) glucose transporter, hexokinase 2, glucagon, growth
      hormone, insulin receptor substrate 1 (IRS1), phosphoenolpyruvate carboxykinase,
      hepatic and muscle forms of pyruvate kinase, hepatic phosphofructokinase, the
      apolipoprotein B and the apolipoprotein A2 cluster, lipoprotein lipase, hepatic
      triglyceride lipase, the very-low-density-lipoprotein receptor, and the Pima
      insulin resistance locus on chromosome 4. For several candidates, no specific
      informative marker was available; consequently, we tested the surrounding region
      with highly informative markers. These regions included the diabetes-associated
      ras-like gene, rad, and the cholesterol ester-transfer gene, both mapped to
      chromosome 16. Additionally, we tested for linkage with markers at the tumor
      necrosis factor-alpha gene and the Friedreich's ataxia region. All regions were
      tested for linkage with microsatellite polymorphisms in > 450 individuals from a
      minimum of 16 Caucasian families under parametric (LINKAGE 5.1) and nonparametric
      (affected pedigree member) models.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589824
TI  - A defective stimulus-secretion coupling rather than glucotoxicity mediates the
      impaired insulin secretion in the mildly diabetic F1 hybrids of GK-Wistar rats.
AB  - Adult F1 hybrids of male GK and female Wistar control rats exhibit mild,
      spontaneous non-insulin-dependent diabetes mellitus characterized by impaired
      glucose-induced insulin secretion. Using isolated pancreatic islets of hybrid
      rats, we first studied whether impaired glucose-induced insulin response is
      present not only in adult but also in neonatal rats. Furthermore, we investigated
      whether the impaired glucose-induced insulin response can be restored by long
      term normalization of glycemia. Both 1-week- and 2- to 3-month-old hybrid rats
      had similar body weights but increased fed blood glucose levels (P < 0.05)
      compared with age-matched control rats. At 5.5 mmol/l glucose, insulin release
      was two- to threefold lower in isolated islets of hybrid than in control rats of
      both age groups (P < 0.05). At 16.7 mmol/l glucose, insulin secretion from hybrid
      islets was approximately 25% of that from control islets of both 1-week- and 2-
      to 3-month-old rats. For the second objective, batches of 250 islets from hybrid
      or control rats were transplanted under the kidney capsule of athymic,
      normoglycemic nude mice and maintained there for 4 weeks. Perfusion of kidneys
      demonstrated that glucose-induced (16.7 mmol/l) insulin secretion was impaired
      markedly in hybrid grafts compared with that in control grafts (0.66 +/- 0.23 vs.
      1.8 +/- 0.38 pmol/20 min; P < 0.01), whereas stimulation by 20 mmol/l arginine
      resulted in similar insulin responses in both groups. The volumes of the grafted
      islets were similar in kidneys bearing either control or hybrid islets.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589825
TI  - Phosphofructokinase isozymes in pancreatic islets and clonal beta-cells (INS-1).
AB  - Normal insulin secretion is oscillatory in vivo, and the oscillations are
      impaired in type II diabetes. We and others have shown oscillations in insulin
      secretion from isolated perifused islets stimulated with glucose, and in this
      study we show oscillations in insulin secretion from the glucose-sensitive clonal
      beta-cell line INS-1. We have proposed that the oscillatory insulin secretion may
      be caused by spontaneous oscillations of glycolysis and the ATP:ADP ratio in the
      beta-cell, analogous to those seen in glycolyzing muscle extracts. The mechanism
      of the latter involves autocatalytic activation of the key regulatory enzyme,
      phosphofructokinase (PFK), by its product fructose 1,6-bisphosphate (F16BP).
      However, of the three PFK subunit isoforms (M-[muscle], L-[liver], and C-type,
      predominant in fibroblasts), only M-type is activated by micromolar F16BP at near
      physiological conditions. We therefore studied PFK isoforms in the beta-cell.
      Western analysis of PFK subunits in isolated rat islets and INS-1 cells showed
      the presence of M-type, as well as C-type and perhaps lesser amounts of L-type.
      Kinetic studies of PFK activity in INS-1 cell extracts showed strong activation
      by micromolar concentrations of F16BP at near-physiological concentrations of ATP
      (several millimolar) and AMP and fructose 6-phosphate (micromolar), indicative of
      the M-type isoform. Activation by submicromolar concentrations of fructose 2,6
      bisphosphate (F26BP) and potent inhibition by citrate were also observed. The
      F16BP-stimulatable activity was about one-half of the F26BP-stimulatable
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589826
TI  - Pancreatic islet cell cytoplasmic antibody in diabetes is represented by
      antibodies to islet cell antigen 512 and glutamic acid decarboxylase.
AB  - The presence of serum islet cell cytoplasmic antibodies (ICAs) is a standard
      autoimmune marker for insulin-dependent diabetes mellitus (IDDM). The antigenic
      molecule(s) responsible for ICA has not been identified, although antibodies to
      the 65-kDa isoform of glutamic acid decarboxylase (GAD65) do contribute. We
      tested 129 IDDM sera for antibodies to ICA512 (anti-ICA512), antibodies to GAD
      (anti-GAD), and ICAs; we tested for inhibition of ICAs with purified recombinant
      ICA512 and sheep brain GAD; and we tested for immunofluorescence reactivity on
      COS7 cells transfected with cDNA clones encoding ICA512 and GAD65. The results
      were that anti-ICA512 antibodies contribute to ICA reactivity and that these, in
      combination with anti-GAD antibodies, account for most ICA reactivity in IDDM.
      Anti-ICA512 antibodies were present at a frequency of 51% in 61 patients with
      early-onset IDDM (age of onset < or = 20 years) of short duration (< or = 1
      month) but only in 9% of 68 patients with an onset age of > 20 years and/or a
      disease duration of > 1 month. The frequency of anti-GAD antibodies in these sera
      was similar irrespective of duration or age of onset. Anti-ICA512 and anti-GAD
      antibodies were demonstrable by indirect immunofluorescence on transfected COS7
      cells, and ICA could be inhibited using either recombinant ICA512 or purified
      brain GAD. We conclude that anti-ICA512 and anti-GAD antibodies contribute to ICA
      reactivity and that anti-ICA512 antibodies account for the increased frequency of
      ICA reactivity in early-onset IDDM of short duration.

PMID- 7589827
TI  - Insulin gene 5' flanking polymorphism. Length of class 1 alleles in number of
      repeat units.
AB  - The 5' flanking polymorphism (5'FP) is a minisatellite, variable number of tandem
      repeat (VNTR) locus adjacent to the 5' end of the insulin gene (INS). Alleles of
      the 5'FP are highly variable in length but fall into three discrete size classes.
      The shortest, or class 1, alleles are associated with insulin-dependent diabetes
      mellitus (IDDM). Here we present a polymerase chain reaction (PCR)-based
      technique for subtyping 5'FP class 1 alleles by determining their exact lengths
      in number of repeat units (RUs). The technique resolves small length differences
      not detectable by Southern blot and produces a frequency distribution of class 1
      allele lengths, which serve as subtypes of the crude class 1 category. We have
      applied the technique to 132 Caucasian families with IDDM offspring and have
      found that the lengths of 5'FP class 1 alleles form a quasi-continuous
      distribution with three distinct modes. We also found precise correlation between
      class 1 allele length and the allele present on the same chromosome at HUMTH01, a
      second VNTR locus in the INS region. Specifically, each of the four common
      alleles of HUMTH01 exhibited near-total association with a narrow size range
      belonging to one of the three components of the class 1 distribution. We discuss
      these results in relation to the population history of the 5'FP and INS region
      haplotypes and in relation to IDDM susceptibility in the INS region.

PMID- 7589828
TI  - Albuminuria and poor glycemic control predict mortality in NIDDM.
AB  - The impact of microalbuminuria and macroalbuminuria on mortality was evaluated
      prospectively in 328 Caucasian patients with non-insulin-dependent diabetes
      mellitus (NIDDM) followed for 5 years. One hundred ninety-one (109 men and 82
      women) patients with normoalbuminuria (albumin excretion rate [AER] < 30 mg/24
      h), 86 (50 men and 36 women) patients with microalbuminuria (AER 30-299 mg/24 h),
      and 51 (43 men and 8 women) patients with macroalbuminuria (AER > or = 300 mg/24
      h) < 66 years old at entry were followed from 1987 until death or until 1 January
      1993. Mean age at entry was 54 (SD 9) years. In January 1993, 8% of patients with
      normoalbuminuria, 20% of patients with microalbuminuria, and 35% of patients with
      macroalbuminuria had died (predominantly from cardiovascular disease) (P < 0.01
      [normoalbuminuria versus micro- and macroalbuminuria] and P < 0.05
      [microalbuminuria versus macroalbuminuria]). Cox multiple regression analysis
      revealed significant predictors of all-cause mortality to be preexisting coronary
      heart disease (relative risk [95% confidence interval]), 2.9 (1.6-5.1); log10AER
      (factor 10), 1.9 (1.4-2.6); HbA1c level (%), 1.2 (1.0-1.4); and age (years), 1.08
      (1.03-1.13). Significant predictors of cardiovascular mortality included
      preexisting coronary heart disease, 6.1 (2.8-13.5); macroalbuminuria, 2.5 (1.1
      5.8); HbA1c level (%), 1.3 (1.1-1.6); and systolic blood pressure (10 mmHg), 1.2
      (1.0-1.4). Univariate Cox survival analysis in the normoalbuminuric group
      revealed that AER above the median of 8 mg/24 h was associated with an increased
      all-cause mortality risk of 2.7 (0.93-7.69) (P = 0.07).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7589831
TI  - High-glucose--triggered apoptosis in cultured endothelial cells.
AB  - High ambient glucose concentration, linked to vascular complications in diabetes
      in vivo, modulates mRNA expression of fibronectin, collagen, tissue-type
      plasminogen activator, and plasminogen activator inhibitor and induces delayed
      replication and excess cell death in cultured vascular endothelial cells. To
      determine the role of high ambient glucose (30 mmol/l) in apoptosis, paired
      cultures of individual isolates of human umbilical vein endothelial cells
      (HUVECs) were exposed to both high (30 mmol/l) and low (5 mmol/l) concentrations
      of glucose for short-term (24, 48, and 72 h) and long-term (13 +/- 1 days)
      experiments. Incubation of HUVECs with high glucose for > 48 h increased DNA
      fragmentation (13.7 +/- 6.5% of total DNA, mean +/- SD) versus cultures kept in 5
      mmol/l glucose (10.9 +/- 5.6%, P < 0.005), as measured by [3H]thymidine assays.
      Data were confirmed by apoptosis-specific fluorescence-activated cell sorter
      analysis of confluent HUVEC cultures, which displayed after long-term exposure to
      30 mmol/l glucose a 1.5-fold higher prevalence of apoptosis than control cultures
      exposed to 5 mmol/l glucose (P < 0.005). In contrast, no increase in DNA
      fragmentation in response to 30 mmol/l glucose was seen for standardized cell
      lines (K 562, P 815, YT) and fibroblasts. Expression of clusterin mRNA,
      originally reported to be a molecular marker of apoptosis, was only slightly
      affected by short-term (24-h) high-glucose exposure but was significantly reduced
      after long-term incubation in 30 mmol/l glucose (82.2 +/- 13.8% of control)
      versus 5 mmol/l glucose, which questions the role of clusterin gene expression as
      a marker of apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589829
TI  - Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp
      studies leads to similar activation of insulin receptor kinase in skeletal muscle
      of subjects with and without NIDDM.
AB  - The role of skeletal muscle insulin receptor kinase in the pathogenesis of non
      insulin-dependent diabetes mellitus (NIDDM) was investigated. Muscle biopsies
      from 13 patients with NIDDM and 10 control subjects at fasting serum insulin
      concentrations and approximately 1,000 pmol/l steady-state serum insulin during
      euglycemic hyperinsulinemic clamps were immediately frozen. The biopsies were
      then solubilized, and the receptors were immobilized to anti-insulin receptor
      antibody-coated microwells. Receptor kinase and binding activities were
      consecutively measured in these wells. The increase in serum insulin
      concentration (73 +/- 14 to 1,004 +/- 83 and 45 +/- 7 to 1,07 +/- 77 pmol/l in
      the NIDDM and control groups, respectively) had similar effects on receptor
      kinase activity in both study groups (12 +/- 1 to 42 +/- 5 and 12 +/- 2 to 47 +/-
      5 amol P.fmol binding activity-1. min-1 in the NIDDM and control groups,
      respectively). Moreover, by selecting only the receptors that bound to anti
      phosphotyrosine antibody, we found similar hyperinsulinemia-induced increases of
      this receptor fraction and its kinase activity in both study groups. In vitro
      activation of the immobilized receptors with 2 mmol/l ATP and insulin further
      increased their kinase activity to almost similar levels, independently of
      whether they had been previously stimulated in vivo or were from diabetic or
      nondiabetic subjects. Compared with this activity reached in vitro, the kinase
      activity obtained by in vivo stimulation at the clamp insulin concentration was
      only approximately 12%, because most receptors remained inactive and only a few
      reached almost the in vitro activation level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589832
TI  - Upregulated hexokinase activity in isolated islets from diabetic 90%
      pancreatectomized rats.
AB  - Glucokinase is the beta-cell glucose sensor, i.e., the site in glucose metabolism
      that determines the glucose set-point (sensitivity) for insulin secretion.
      Hexokinase is also present, but it normally contributes little to glucose
      metabolism because of end-product inhibition by glucose 6-phosphate. There is a
      lowered glucose set-point for insulin secretion in 90% pancreatectomized (Px)
      diabetic rats. We investigated the mechanism by measuring hexokinase and
      glucokinase activity in islet extracts. Glucokinase activity was minimally raised
      in Px islets (Vmax 125% of sham-operated control rats). In contrast, hexokinase
      Vmax was 250% of the control value, suggesting that the increased hexokinase
      activity caused the beta-cell glucose hypersensitivity. Additional evidence was
      obtained with a 40-h fast that was performed because of a previous observation
      that the inhibitory effect of fasting on insulin secretion was impaired in Px
      rats. Glucokinase activity fell normally in the Px rats (32 +/- 4% reduction in
      sham vs. 37 +/- 4% in Px rats) as opposed to hexokinase activity, which was
      unaffected in either group. In summary, a feature of hyperglycemia is upregulated
      islet hexokinase activity. The result is that hexokinase assumes partial control
      over the glucose set-point for insulin secretion. As such, regulatory effects on
      insulin secretion, such as fasting, that are mediated through glucokinase
      activity may be altered.

PMID- 7589833
TI  - Residual beta-cell function and HLA-A24 in IDDM. Markers of glycemic control and
      subsequent development of diabetic retinopathy.
AB  - To identify risk factors for diabetic retinopathy in insulin-dependent diabetes
      mellitus (IDDM), we studied the relationships among residual beta-cell function,
      human leukocyte antigen (HLA), long-term glycemic control, and development of
      diabetic retinopathy in 128 IDDM patients. Residual beta-cell function was
      assessed by serum C-peptide immunoreactivity (CPR) response to a 100-g oral
      glucose load (delta CPR). The patients were stratified into three groups: those
      with delta CPR of < 0.033 nmol/l (group 1, n = 50), those with delta CPR of 0.033
      0.1 nmol/l (group 2, n = 38), and those with delta CPR of > 0.1 nmol/l (group 3,
      n = 40). The cumulative incidence rate of background retinopathy was higher in
      the order of groups 1, 2, and 3 (P = 0.032). Group 1 progressed to
      preproliferative retinopathy at an earlier stage than did groups 2 and 3 combined
      (P = 0.028). Further progression to proliferative retinopathy tended to be
      earlier in group 1 than in groups 2 and 3 combined (P = 0.083). The mean HbA1c
      value rose from 9.01 +/- 1.06% (mean +/- SD) in group 3 to 9.75 +/- 0.79% in
      group 2 to 10.48 +/- 1.12% in group 1 (P < 0.0001). In group 1, 89.6% of the
      patients had HLA-A24, whereas 50 and 43.6% of the patients had this antigen in
      groups 2 and 3 respectively (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589830
TI  - Impaired insulin-induced platelet antiaggregating effect in obesity and in obese
      NIDDM patients.
AB  - To investigate the effects of insulin on platelets in obesity and in non-insulin
      dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we
      determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'
      cyclic monophosphate) content in platelet-rich plasma obtained from nine obese
      subjects and nine age-matched healthy volunteers and from eight NIDDM obese
      patients and nine age-matched healthy volunteers after a 3-min incubation with
      human recombinant insulin (0, 240, 480, 960, and 1,920 pmol/l). Platelet
      aggregation was evaluated using different ADP doses to measure the ADP
      concentration determined on the basis of a dose-response curve necessary to
      elicit a maximal aggregation of 50% (ED50). Insulin induced a dose-dependent
      decrease of platelet aggregation to ADP (P = 0.0001) in healthy subjects. A
      significant effect was evident starting from an insulin concentration of 240
      pmol/l. On the contrary, in insulin-resistant subjects, insulin reduced platelet
      sensitivity to ADP only at a concentration of 1,920 pmol/l. When ADP ED50 values
      obtained in platelet-rich plasma incubated with insulin were expressed in
      percentage of the ADP ED50 values obtained in platelet-rich plasma without
      insulin, considered as 100%, we observed that ADP ED50 with 1,920 pmol/l insulin
      was 153.6 +/- 13.2% in the younger healthy subject group (P = 0.004), 150.0 +/-
      3.8% in the older healthy subject group (P = 0.0001), 116.1 +/- 6.1% in obese
      subjects (P = 0.031), and 120.0 +/- 8.6% in NIDDM patients (P = 0.05). In healthy
      subjects, insulin induced a dose-dependent increase of platelet cGMP (P =
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589836
TI  - IgG antibodies to bovine serum albumin are not increased in children with IDDM.
AB  - IgG antibodies to bovine serum albumin (BSA) were measured in 91 serum samples
      from children 4-17 years of age with newly diagnosed insulin-dependent diabetes
      mellitus (IDDM). A total of 80 healthy 12-year-old children served as control
      subjects. BSA antibody values > 3 SDs were obtained in 6 IDDM patients and 3
      control subjects (P = 0.50), and values > 2 SDs were obtained in 12 IDDM patients
      and 4 control subjects (P = 0.11). In conclusion, IgG antibodies to BSA were not
      significantly increased at onset of diabetes.

PMID- 7589834
TI  - ICA512 autoantibody radioassay.
AB  - As part of a general program of screening islet expression libraries we have
      identified a clone from a lambda gt11 human islet expression library that reacts
      with human diabetic sera and, upon sequencing, was determined to be the
      neuroendocrine islet autoantigen ICA512 (islet cell antigen 512). In the current
      communication, we describe the development of a radioassay for autoantibodies to
      ICA512 (ICA512AA) using in vitro transcribed and translated protein for
      production of labeled antigen. Our initial results indicate that this radioassay
      is significantly more sensitive than the enzyme-linked immunosorbant assay, which
      uses a COOH-terminal fragment of ICA512. The ICA512AA radioassay uses a 96-well
      format with membrane separation of antibody bound from free antigen and should be
      readily adaptable to automated large-scale screening. Only 7 microliters of serum
      is required for triplicate determinations. In order to determine the specificity
      and sensitivity of this assay and estimate its positive predictive value, we have
      studied 42 new-onset diabetic patients, 33 first-degree relatives of diabetic
      patients followed to diabetes, 694 islet cell antibody-negative (ICA-) relatives,
      and 205 normal control subjects. Thirty-eight percent of new-onset patients and
      48% of relatives followed to diabetes express autoantibodies to ICA512 exceeding
      the 99th percentile of the normal control subjects. In contrast, only 1.4% of ICA
      first-degree relatives were positive for ICA512 autoantibodies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589837
TI  - Diabetes, diabetes, and the American Diabetes Association.

PMID- 7589835
TI  - Hyperglycemia activates glucose transport in rat skeletal muscle via a Ca(2+)
      dependent mechanism.
AB  - We investigated the acute effect of hyperglycemia on 3-O-methylglucose transport
      in isolated rat epitrochlearis muscles. High levels of glucose (20 mmol/l)
      induced an approximately twofold increase in the rate of glucose transport when
      compared with muscles exposed to a low level of glucose (8 mmol/l) (P < 0.001).
      The hyperglycemic effect was additive to the effects of both insulin and exercise
      on the glucose transport rates. Dantrolene (25 mumol/l), a potent inhibitor of
      Ca2+ release from the sarcoplasmic reticulum, blocked the ability of
      hyperglycemia to increase glucose transport by 73% (P < 0.01). Although
      dantrolene had no effect on the non-insulin-stimulated or the insulin-stimulated
      glucose transport rates during normoglycemic conditions, the effect of exercise
      was completely blocked in the presence of dantrolene (P < 0.01). Inhibition of
      phosphatidylinositol (PI) 3-kinase by wortmannin (500 nmol/l) had no effect on
      the activation of glucose transport by hyperglycemia, whereas the insulin
      stimulated glucose transport was completely abolished (P < 0.001). These findings
      suggest that hyperglycemia activates glucose transport by a Ca(2+)-dependent
      activation of glucose transport does not involve the activation of PI 3-kinase
      and is separate from the mass-action effect of glucose on glucose transport.

PMID- 7589838
TI  - Clinical trials of diabetic neuropathy: past, present, and future.
AB  - This article reviews current knowledge of the etiology of diabetic neuropathy and
      the outcomes and limitations of previous trials and discusses future directions
      for the investigation of its prevention and treatment. Proposed mechanisms for
      the development of diabetic neuropathy have been widely studied. It has been
      shown that there is improvement of nerve function associated with some short-term
      clinical trials of treatments that address a number of possible etiologic
      pathways. Improvement of morphometry has also been demonstrated in some short
      term clinical trials. However, with the exception of the Diabetes Control and
      Complications Trial (DCCT), long-term trials with adequate statistical power to
      evaluate clinical outcome endpoints have not been conducted. The changes in nerve
      function are similar in most of the clinical trials. For instance, in four
      clinical trials directed at separate mechanisms (improved glucose control, high
      myo-inositol diet, therapy with an aldose reductase inhibitor, and therapy with
      supplementary gamma-linolenic acid), a similar improvement in peroneal motor
      velocity of 1-2 m/s is observed. This implies that each of the proposed
      mechanisms contributes equally to the development of neuropathy or that there is
      some redundancy to their mechanisms. In addition to an etiologic approach,
      nonspecific neural stimulants, such as gangliosides and nerve growth factors,
      have also been investigated for the treatment of diabetic neuropathy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589839
TI  - Mechanisms of increased skeletal muscle glucose transport activity after an oral
      glucose load in rats.
AB  - It is not known whether the insulin-induced changes in the skeletal muscle
      glucose transport system occur under physiological circumstances. To clarify
      whether, by which mechanisms, and for how long skeletal muscle glucose transport
      activity is increased after an oral glucose load (OGL), we prepared plasma
      membrane (PM) and microsomal membrane (MsM) vesicles from hindlimb muscles of
      Sprague-Dawley rats either in the fasting state or 30, 60, 90, or 120 min after
      an OGL (2 g/kg body wt). In both PM and MsM, we measured the total number of
      glucose transporters (Ro), GLUT4, and GLUT1. In the PM, we also determined
      glucose influx (Vmax) and carrier turnover number (TN), an index of average
      transporter intrinsic activity, (TN = Vmax/Ro). The Vmax significantly increased
      after OGL, was maximal at 30 min, and returned to baseline at 90 min. The Ro and
      GLUT4 in the PM also increased significantly, with the maximum level reached at
      60 min. The TN was increased only at 30 min. The changes in Ro and GLUT4 in the
      MsM were opposite to those in the PM, consistent with translocation of GLUT4 from
      an intracellular pool to the PM. In conclusion, an OGL induces an increase in the
      skeletal muscle glucose transport activity. This increase is associated with the
      translocation of GLUT4 from the MsM to the PM and a more transient increase in
      the average transporter TN. Our results show that transporter translocation and
      activation occur under physiological circumstances.

PMID- 7589841
TI  - NIDDM is the major cause of diabetic end-stage renal disease. More evidence from
      a tri-ethnic community.
AB  - Diabetes is the single largest cause of end-stage renal disease (ESRD) in adults
      in the U.S. Insulin-dependent diabetes mellitus (IDDM) has been recognized for
      some time as an important cause of ESRD, but non-insulin-dependent diabetes
      mellitus (NIDDM) has been assumed, until recently, to rarely cause ESRD. The
      objective of this study is to determine the incidence of treatment of diabetic
      ESRD by diabetic type for three ethnic/racial groups: non-Hispanic whites,
      African-Americans, and Mexican-Americans. A population-based incidence cohort was
      assembled from all dialysis centers in Bexar (San Antonio) and Dallas counties in
      Texas. All patients with diabetic ESRD beginning dialysis between 1 December 1987
      (Bexar) or 1 December 1988 (Dallas) and 31 July 1991 were identified. All non
      hispanic whites and African-Americans and a 1/2 random sample of Mexican
      Americans were approached for enrollment. Individuals were confirmed to have
      diabetes using the World Health Organization criteria. Diabetes typing was done
      using a computerized historical algorithm. Age-specific and age-adjusted
      incidence rates were obtained by diabetic type and ethnic/racial group. NIDDM
      causes the majority of diabetic ESRD: 59.5% for non-Hispanic whites, 92.8% for
      Mexican-Americans, and 84.3% for African-Americans. Mexican-Americans and African
      Americans, respectively, have 6.1 and 6.5 times higher incidence of treatment for
      diabetic ESRD than non-Hispanic whites. NIDDM results in more ESRD than does
      IDDM. Minorities (African-Americans and Mexican-Americans) are at increased risk,
      and programs aimed at prevention of NIDDM-related ESRD must focus on them.

PMID- 7589840
TI  - Pancreatic islet GLUT2 glucose transporter mRNA and protein expression in humans
      with and without NIDDM.
AB  - GLUT2 glucose transporter mRNA has been shown to be underexpressed in pancreatic
      islets of numerous animal models of non-insulin-dependent diabetes mellitus
      (NIDDM). It has been proposed that this molecular defect contributes to the
      pathogenesis of diabetes, although information concerning the expression of GLUT2
      in human pancreatic islet tissue is lacking. In contrast to the high abundance of
      GLUT2 in rat islets, human islets were found to express distinctly low levels of
      this glucose transporter mRNA and protein. Thus, a sensitive competitive reverse
      transcription-polymerase chain reaction assay was developed to quantify human
      GLUT2 mRNA. We obtained pancreases from 4 human organ donors with previously
      diagnosed NIDDM and 11 nondiabetic donors and found no significant differences in
      GLUT2 mRNA between the two groups. GLUT2 mRNA was 0.24 +/- 0.08 amol/micrograms
      RNA (mean +/- SE) in pancreases from humans with diabetes and 0.27 +/- 0.06
      amol/microgram RNA in those without this diagnosis. Similarly, human pancreatic
      islet GLUT2 protein was measured by immunoblot and found to be present at similar
      levels in two individuals with diabetes relative to six control samples. These
      results thus demonstrate the existence of species differences in the abundance of
      islet GLUT2 mRNA and protein. Furthermore, the analysis of islet GLUT2 in a small
      sample of human organ donors with and without diabetes raises the possibility
      that decreased beta-cell GLUT2 may not represent a widespread feature of humans
      with NIDDM.

PMID- 7589842
TI  - Action profile of cobalt(III)-insulin. A novel principle of protraction of
      potential use for basal insulin delivery.
AB  - The Co(3+)-insulin hexamer is an extraordinary stable insulin hexamer that has no
      affinity for the insulin receptor per se but is converted into active insulin in
      vivo. In the present study, we evaluated the action profile of Co(3+)-insulin
      after subcutaneous injection into nondiabetic pigs and showed that the Co(3+)
      hexamer does not dissociate before absorption. After absorption, Co(3+)-insulin
      is accumulated in the bloodstream because the complex is distributed and
      eliminated more slowly than human insulin. The degree of protraction of Co(3+)
      insulin is similar to that of NPH insulin when evaluated in an euglycemic glucose
      clamp. We suggest that the long plasma half-life and a gradual in vivo activation
      contribute to prolong the effect of Co(3+)-insulin. The Co(3+)-insulin hexamer
      provides a novel principle of protraction of potential use for basal insulin
      delivery to the diabetic patient.

PMID- 7589843
TI  - Decreased insulin secretion and increased insulin resistance are independently
      related to the 7-year risk of NIDDM in Mexican-Americans.
AB  - The relative importance of insulin resistance and abnormal insulin secretion as
      risk factors for the development of non-insulin-dependent diabetes mellitus
      (NIDDM) is still controversial. Few data are available on insulin secretion as a
      risk factor for the development of NIDDM, especially in subjects with normal
      glucose tolerance. We examined the relation of fasting insulin (as a marker of
      insulin resistance) and the ratio of change in insulin to change in glucose
      during the first 30 min after glucose ingestion (delta I30/delta G30) (as a
      marker of insulin secretion) as predictors of the 7-year development of NIDDM in
      714 initially nondiabetic Mexican-Americans. NIDDM developed in 99 subjects. The
      relative risk of NIDDM increased with higher quartiles of fasting insulin
      (quartile 1 [low], 1.0; quartile 2, 1.5; quartile 3, 2.0; and quartile 4 [high],
      3.7; P < 0.0001) and lower delta I30/delta G30 (quartile 1 [low], 6.9; quartile
      2, 1.9; quartile 3, 1.1; quartile 4 [high], 1.0; P < 0.001). Subjects with both
      increased fasting insulin and decreased delta I30/delta G30 had independent
      increases in NIDDM incidence (P < 0.001). Further, when we stratified subjects by
      baseline glucose tolerance, both increased fasting insulin and decreased delta
      I30/delta G30 significantly predicted NIDDM in subjects with both impaired and
      normal glucose tolerance at baseline. We conclude that both decreased insulin
      secretion (as assessed by low delta I30/delta G30) and increased insulin
      resistance (as assessed by fasting insulin) predict the development of NIDDM in
      Mexican-Americans, a group previously characterized as having hyperinsulinemia
      and insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589844
TI  - Emv30null NOD-scid mice. An improved host for adoptive transfer of autoimmune
      diabetes and growth of human lymphohematopoietic cells.
AB  - When used as hosts in passive transfer experiments, a stock of NOD/Lt mice
      congenic for the severe combined immunodeficiency (scid) mutation have provided
      great insight to the contributions of various T-cell populations in the
      pathogenesis of autoimmune insulin-dependent diabetes mellitus (IDDM). Moreover,
      NOD-scid mice support higher levels of human lymphohematopoietic cell growth than
      the C.B-17-scid strain in which the mutation originated. However, the ability to
      perform long-term lymphohematopoietic repopulation studies in the NOD-scid stock
      has been limited by the fact that most of these mice develop lethal thymic
      lymphomas beginning at 20 weeks of age. These thymic lymphomas are characterized
      by activation and subsequent genomic reintegrations of Emv30, an endogenous
      murine ecotropic retrovirus unique to the NOD genome. To test the role of this
      endogenous retrovirus in thymomagenesis, we produced a stock of Emv30null NOD
      scid mice by congenic replacement of the proximal end of chromosome 11 with
      genetic material derived from the closely related NOR/Lt strain. Thymic lymphomas
      still initiate in Emv30null NOD-scid females, but their rate of progression is
      significantly retarded since the frequency of tumors weighing between 170 and 910
      mg at 25 weeks of age was reduced to 20.8% vs. 76.2% in Emv30% segregants. The
      thymic lymphomas that did develop in Emv30null NOD-scid mice were not
      characterized by a compensatory increase in mink cell focus-forming proviral
      integrations, which initiate thymomagenesis in other susceptible mouse strains.
      Significantly, the ability of standard NOD T-cells to transfer IDDM to the
      Emv30null NOD-scid stock was not impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589845
TI  - Upregulation of blood-brain barrier GLUT1 glucose transporter protein and mRNA in
      experimental chronic hypoglycemia.
AB  - An in vivo model of chronic hypoglycemia was used to investigate changes in blood
      brain barrier (BBB) glucose transport activity and changes in the expression of
      GLUT1 mRNA and protein in brain microvasculature occurring as an adaptive
      response to low circulating glucose levels. Chronic hypoglycemia was induced in
      rats by constant infusion of insulin via osmotic minipumps; control animals
      received infusions of saline. The criterion for chronic hypoglycemia was an
      average blood glucose concentration of < 2.3 mmol/l (42 mg/dl) after 5 days. The
      average blood glucose concentration at the end of the experimental period in the
      rats selected for study was 2.0 +/- 0.1 mmol/l (36 +/- 1 mg/dl) vs. 4.9 +/- 0.1
      mmol/l (88 +/- 1 mg/dl) in the controls. Internal carotid artery perfusion
      studies demonstrated an increase in the BBB permeability-surface area (PS)
      product of 40% (P < 0.0005) in the chronically hypoglycemic animals as compared
      with controls. Western blotting of solubilized isolated brain capillaries
      demonstrated a 51% increase (P < 0.05) in immunoreactive BBB GLUT1 in the
      chronically hypoglycemic rats, and Northern blotting of whole-brain poly(A+) mRNA
      revealed a 50% increase in the GLUT1-to-actin ratio in the insulin-treated group
      (P < 0.05). Northern blotting analysis of microvessel-depleted total brain
      poly(A+) showed that the increase in GLUT1 mRNA in the chronically hypoglycemic
      rats was restricted to the BBB. The present study demonstrates increased
      expression of GLUT1 mRNA and protein at the BBB in chronic hypoglycemia and
      suggests that this increase is responsible for the compensatory increase in BBB
      glucose transport activity that occurs with chronically low circulating blood
      glucose levels.

PMID- 7589846
TI  - Low birth weight. A risk factor for development of diabetic nephropathy?
AB  - It has been demonstrated that intrauterine growth retardation, defined as birth
      weight below the 10th percentile, gives rise to a reduction in nephron number.
      Oligonephropathy has been suggested to increase the risk for systemic and
      glomerular hypertension in adult life as well as enhance risk for expression of
      renal disease after exposure to potentially injurious renal stimuli. The aim of
      this study was to determine if low birth weight is a risk factor for development
      of diabetic nephropathy. In a case-control study, we investigated 184 (110 men)
      insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy
      (persistent albuminuria > 300 mg/24 h) (age [mean +/- SD] 41.0 +/- 9.3 years,
      duration of diabetes 26.9 +/- 8.2 years) and 182 (111 men) normoalbuminuric (< 30
      mg/24 h) IDDM patients (age 42.1 +/- 9.8 years, duration of diabetes 25.8 +/- 8.6
      years). Information about weight at birth was obtained from the midwife's
      original registrations. In women below the 10th percentile in birth weight (< or
      = 2,700 g, n = 16), 75% had nephropathy compared with only 35% among patients
      whose birth weights were above the 90th percentile (> or = 4,000 g, n = 17) (P =
      0.05). In men below the 10th percentile in birth weight (< or = 2,910 g, n = 22),
      the prevalence of patients with nephropathy (50%) was similar to the prevalence
      among patients above the 90th percentile in birth weight (> or = 4,200 g, n = 24)
      (54%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589847
TI  - Localization of MODY3 to a 5-cM region of human chromosome 12.
AB  - Maturity-onset diabetes of the young (MODY) is a heterogeneous disorder that
      appears to be characterized by a primary defect in insulin secretion. Mutations
      in an unknown locus (MODY1) on chromosome 20 and the glucokinase gene (MODY2) on
      chromosome 7 can cause this form of non-insulin-dependent diabetes. Recent
      genetic studies have identified a third locus on chromosome 12 (MODY3) that is
      linked to MODY in a group of French families. We have identified three families
      from Denmark, Germany, and the U.S. (Michigan) showing evidence of linkage with
      MODY3 and a family from Japan showing suggestive evidence. Analysis of key
      recombinants in these families localized MODY3 to a 5-cM interval between the
      markers D12S86 and D12S807/D12S820.

PMID- 7589848
TI  - Aberrant activation of CD8+ T-cell and CD8+ T-cell subsets in patients with newly
      diagnosed IDDM.
AB  - Two- and three-color cytofluorimetric techniques were used to study the
      expression patterns of the activation antigen HLA-DR on peripheral blood
      immunoregulatory T-cells from 25 patients with newly diagnosed insulin-dependent
      diabetes mellitus (IDDM) and 14 age- and sex-matched control subjects. The mean
      percentage of total activated (CD3+HLA-DR+) T-cells was significantly elevated in
      the IDDM group compared with the control group (P < 0.001). In control subjects,
      basal activation of CD4+ and CD8+ lymphocytes accounted for the low percentage
      levels of activated T-cells. In contrast, the majority of IDDM patients showed an
      unbalanced activation of CD4+ and CD8+ lymphocytes with predominant activation of
      the CD8+ lymphocyte subset. The composition of the activated T-cell fraction was
      dependent on the composition of the total (activated + nonactivated) T-cell
      population, as indicated by the positive correlation between the CD4+/CD8+ T-cell
      ratios in these two cell populations (r = 0.714; P < 0.001). Excessive activation
      of CD8+ T-cells was attributable to similar increases in the proportions of CD8+
      CD45RA+HLA-DR+ (naive) and CD8+CD45RA-HLA-DR+ (memory) cells. Analysis of the
      CD11b-defined subsets revealed predominant activation of CD8+ CD11b- (cytotoxic)
      T-cells; CD8+ CD16+ HLA-DR+ natural killer cells were unchanged. The distribution
      of HLA-DR+ cells among subsets of CD4+ T-cells differed from the pattern in the
      CD8+ population in that selective activation of CD4+ CD45RA- (memory, helper
      inducer) cells accounted for the small increase in activated CD4+ cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589849
TI  - Corticosterone regulation of insulin-like growth factor I, IGF-binding proteins,
      and growth in streptozotocin-induced diabetic rats.
AB  - The experiments reported herein were conducted to determine how corticosterone
      regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding
      protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced
      diabetic rats. Males were bilaterally adrenalectomized (Ax) or sham Ax and given
      intravenous injections of 0, 30, or 65 mg STZ per kg body wt (0, 30, or 65 STZ)
      to induce varying degrees of insulin deficiency and implanted with 100-mg pellets
      containing 0, 40, or 80% corticosterone in cholesterol. Changes in plasma IGFBP
      concentrations were determined by Western ligand blotting or immunoblots. Neither
      IGFBP-5 nor IG-FBP-6 was detected in any of the treatment groups. Plasma IGFBP-2
      was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham
      Ax controls, but plasma IGFBP-3 and -4 were not significantly changed.
      Adrenalectomy had no affect on tibial growth or plasma IGFBP-1 in these animals.
      Plasma IGF-I, IGFBP-1 and -3, and tibial growth were equal among 0, 30, and 65
      STZ Ax rats that did not receive corticosterone. Plasma IGFBP-4 was inversely
      related to the amount of STZ injected in these animals, and IGFBP-2 was elevated
      in those given the high dose of STZ. In the 0 STZ Ax rats, plasma IGF-I and IGFBP
      3 increased in proportion to the corticosterone implant dose, but IGFBP-1 was
      unaffected. By contrast, IGF-I and IGFBP-3 were unaltered by corticosterone in
      the 30 STZ Ax rats, and IGFBP-1 increased in proportion with the dose of
      corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589850
TI  - Regulation of hexokinase II gene transcription and glucose phosphorylation by
      catecholamines, cyclic AMP, and insulin.
AB  - The hexokinases, by converting glucose to glucose-6-phosphate, help maintain the
      downhill gradient that results in movement of glucose into cells through the
      facilitative glucose transporters. GLUT4 and hexokinase (HK) II are the major
      transporter and hexokinase isoforms in skeletal muscle, heart, and adipose
      tissue, wherein insulin promotes glucose utilization. To understand whether
      hormones influence the contribution of phosphorylation to cellular glucose
      utilization, we investigated the effects that catecholamines, cyclic AMP (cAMP),
      and insulin have on HKII gene expression in cells representative of muscle (L6
      cells) and brown (BFC-1B cells) and white (3T3-F442A cells) adipose tissues.
      Isoproterenol or the cAMP analog 8-chlorophenylthio-cAMP selectively increase
      HKII gene transcription in L6 cells, as does insulin (Printz RL, Koch S, Potter
      LP, O'Doherty RM, Tiesinga JJ, Moritz S, Granner DK: Hexokinase II mRNA and gene
      structure, regulation by insulin, and evolution. J Biol Chem 268:5209-5219,
      1993), and cause a concentration- and time-dependent increase of HKII mRNA in
      both muscle and fat cell lines without changing HKI mRNA. Isoproterenol and
      insulin also increase the rate of synthesis of HKII protein and increase glucose
      phosphorylation and glucose utilization in L6 cells.

PMID- 7589851
TI  - Enteral enhancement of glucose disposition by both insulin-dependent and insulin
      independent processes. A physiological role of glucagon-like peptide I.
AB  - Glucagon-like peptide I (GLP-I)(7-36) amide is secreted by intestinal L-cells in
      response to food ingestion. GLP-I is a potent insulin secretagogue and also
      inhibits glucagon release. In addition, when given to humans in pharmacological
      amounts, GLP-I increases glucose disposal independent of its effects on islet
      hormone secretion. To test the hypothesis that this extrapancreatic effect of GLP
      I on glucose disposition is present at physiological levels of GLP-I, we
      performed intravenous glucose tolerance tests (IVGTTs) 1 h after the following
      interventions: 1) the ingestion of 50 g fat to stimulate GLP-I secretion or the
      ingestion of water as a control and 2) infusion of GLP-I to attain physiological
      levels or a control infusion of saline. The results of the IVGTTs were analyzed
      using the minimal model technique to determine the insulin sensitivity index (SI)
      and indexes of insulin-independent glucose disposition, glucose effectiveness at
      basal insulin (SG), and glucose effectiveness at zero insulin (GEZI), as well as
      the glucose disappearance constant (k(g)) and the acute insulin response to
      glucose (AIRg). These parameters were compared between conditions of elevated
      circulating GLP-I and control conditions. After ingestion of fat and infusion of
      synthetic hormone, plasma GLP-I increased to similar levels; GLP-I did not change
      with water ingestion or saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589852
TI  - Effects of diabetes and hyperglycemia on the hexosamine synthesis pathway in rat
      muscle and liver.
AB  - In vitro studies suggested that increased flux of glucose through the hexosamine
      biosynthesis pathway (HexNSP) contributes to glucose-induced insulin resistance.
      Glutamine:fructose-6- phosphate amidotransferase (GFAT) catalyzes glucose flux
      via HexSNP; its major products are uridine diphosphate (UDP)-N-acetyl hexosamines
      (UDP-HexNAc). We examined whether streptozotocin (STZ)-induced diabetes (4-10
      days) or sustained hyperglycemia (1-2 h) in normal rats alters absolute or
      relative concentrations of nucleotide-linked sugars in skeletal muscle and liver
      in vivo. UDP-HexNAc and UDP-hexoses (UDP-Hex) were increased and decreased,
      respectively, in muscles of diabetic rats, resulting in an approximately 50%
      increase in the UDP-HexNAc:UDPHex ratio (P < 0.01). No significant changes in
      nucleotide sugars were observed in livers of diabetic rats. In muscles of normal
      rats, UDP-HexNAc concentrations increased (P < 0.01) and UDP-Hex decreased (P <
      0.01) during hyperglycemia. The UDP-HexNAc:UDP-Hex ratio increased approximately
      40% (P < 0.01) and correlated strongly with plasma glucose concentrations.
      Changes in liver were similar to muscle but were less marked. GFAT activity in
      muscle and liver was unaffected by 1-2 h of hyperglycemia. GFAT activity
      decreased 30-50% in muscle, liver, and epididymal fat of diabetic rats, and this
      was reversible with insulin therapy. No significant change in GFAT mRNA
      expression was detected, suggesting post-transcriptional regulation. The data
      suggest that glucose flux via HexNSP increases in muscle during hyperglycemic
      hyperinsulinemia and that the relative flux of glucose via HexNSP is increased in
      muscle in STZ-induced diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589853
TI  - Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat.
AB  - The molecular basis for the beta-cell dysfunction that characterizes non-insulin
      dependent diabetes mellitus (NIDDM) is unknown. The Zucker diabetic fatty (ZDF)
      male rat is a rodent model of NIDDM with a predictable progression from the
      prediabetic to the diabetic state. We are using this model to study beta-cell
      function during the development of diabetes with the goal of identifying genes
      that play a key role in regulating insulin secretion and, thus, may be potential
      targets for therapeutic intervention aimed at preserving or improving beta-cell
      function. As a first step, we have characterized morphology, insulin secretion,
      and pattern of gene expression in islets from prediabetic and diabetic ZDF rats.
      The development of diabetes was associated with changes in islet morphology, and
      the islets of diabetic animals were markedly hypertrophic with multiple irregular
      projections into the surrounding exocrine pancreas. In addition, there were
      multiple defects in the normal pattern of insulin secretion. The islets of
      prediabetic ZDF rats secreted significantly more insulin at each glucose
      concentration tested and showed a leftward shift in the dose-response curve
      relating glucose concentration and insulin secretion. Islets of prediabetic
      animals also demonstrated defects in the normal oscillatory pattern of insulin
      secretion, indicating the presence of impairment of the normal feedback control
      between glucose and insulin secretion. The islets from diabetic animals showed
      further impairment in the ability to respond to a glucose stimulus. Changes in
      gene expression were also evident in islets from prediabetic and diabetic ZDF
      rats compared with age-matched control animals. In prediabetic animals, there was
      no change in insulin mRNA levels. However, there was a significant 30-70%
      reduction in the levels of a large number of other islet mRNAs including
      glucokinase, mitochondrial glycerol-3-phosphate dehydrogenase, voltage-dependent
      Ca2+ and K+ channels, Ca(2+)-ATPase, and transcription factor Islet-1 mRNAs. In
      addition, there was a 40-50% increase in the levels of glucose-6-phosphatase and
      12-lipoxygenase mRNAs. There were further changes in gene expression in the
      islets from diabetic ZDF rats, including a decrease in insulin mRNA levels that
      was associated with reduced islet insulin levels. Our results indicate that
      multiple defects in beta-cell function can be detected in islets of prediabetic
      animals well before the development of hyperglycemia and suggest that changes in
      the normal pattern of gene expression contribute to the development of beta-cell
      dysfunction.

PMID- 7589854
TI  - Growth factor/matrix-induced proliferation of human adult beta-cells.
AB  - Proliferation of human beta-cells in vitro is desirable for both transplantation
      and biological studies. In this study, human pancreatic islets obtained from
      cadavers were kept in tissue culture plates that favored cell attachment. When
      the cells attached to the matrix produced by the rat-bladder carcinoma cell line
      804G, 5'-bromo-2'-deoxyuridine (BrdU) labeling increased from 4.7 +/- 2.5 to 13.2
      +/- 2.2%, while cells simultaneously labeled for insulin and BrdU increased from
      0 to 32%. Addition of the growth factor hepatocyte growth factor/scatter (HGF/SF)
      increased BrdU labeling to 17.5 +/- 1.8 and the percentage of double positive
      (BrdU + insulin) cells to 69%. This is the first in vitro demonstration that
      human beta-cells grown in monolayer culture are able to replicate when exposed to
      selected matrices and growth factors. These experiments add further evidence that
      HGF/SF is an important mitogenic agent for human beta-cells.

PMID- 7589855
TI  - An ATP-sensitive Cl- channel current that is activated by cell swelling, cAMP,
      and glyburide in insulin-secreting cells.
AB  - Although chloride ions are known to modulate insulin release and islet electrical
      activity, the mechanism or mechanisms mediating these effects are unclear.
      However, numerous studies of islet Cl- fluxes have suggested that Cl- movements
      and glucose and sulfonylurea sensitive and are blocked by stilbene-derivative Cl-
      channel blockers. We now show for the first time that insulin-secreting cells
      have a Cl- channel current, which we term ICl,islet. The current is activated by
      hypotonic conditions, 1-10 mumol/l glyburide and 0.5 mmol/l 8-bromoadenosine
      3':5'-cyclic monophosphate sodium. ICl,islet is mediated by Cl- channels, since
      replacing [Cl-]o with less permeant aspartate reduces current amplitude and
      depolarizes its reversal potential. In addition, 100 mumol/l 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or glyburide, which blocks
      the Cl- channels of other cell types, block ICl,islet. Reducing [ATP]i reduces
      the amplitude of the current, suggesting that it may be under metabolic control.
      The current is time-independent and shows strong outward-rectification beyond
      approximately 0 mV. At potentials associated with the silent phase of islet
      electrical activity (approximately -65 mV), ICl,islet mediates a large inward
      current, which would be expected to depolarize islet membrane potential. Thus,
      activation of this novel current by increased intracellular cAMP, sulfonylureas,
      or ATP may contribute to the well-known depolarizing effects of these agents.

PMID- 7589857
TI  - Outcomes that matter.

PMID- 7589856
TI  - The ob gene and insulin. A relationship leading to clues to the understanding of
      obesity.
AB  - Obesity and non-insulin-dependent diabetes are estimated to affect millions of
      people in the world. This pathology is multifactorial, comprising complex
      interactions of genetic and environmental factors and lacking a specific therapy.
      Great interest arose from the recent discovery of the ob gene expressed only in
      adipose tissue and coding for a protein that appears to regulate adiposity,
      potentially by acting as a satiety factor. We report here that in normal rats, ob
      mRNA is respectively up- or downregulated by a rise in insulinemia (induced by 2
      day insulin infusion while maintaining euglycemia) or a decrease in insulinemia
      (induced by a 3-day fast). Our results also show that in genetically obese fa/fa
      rats studied longitudinally, white adipose tissue ob mRNA levels increase in
      parallel with early occurring and steadily increasing hyperinsulinemia. This
      results in adult obese animals having markedly higher ob mRNA levels than age
      matched normoinsulinemic lean rats. Furthermore, in adult obese rats, ob mRNA
      escapes down-regulation as normalization of hyperinsulinemia due to fasting fails
      to reduce the high ob mRNA levels.

PMID- 7589858
TI  - Long-term outcome of saliva-control surgery.
AB  - Thirty-nine patients who had undergone transposition of the submandibular ducts
      and unilateral ligation of a parotid duct for saliva control were followed up six
      years after surgery. Overall improvement was documented according to a drooling
      quotient, drooling severity and drooling frequency measures. Despite this
      superficially favourable outcome, a significant proportion of patients (39 per
      cent) or their caregivers had not found the surgery helpful. Complications
      included ranula formation, complaints of dry mouth, difficulty with swallowing,
      and changes in the consistency of oral secretions. More knowledge is needed of
      the likely outcomes of this procedure in individual patients, so that appropriate
      advice can be given and complications minimised.

PMID- 7589859
TI  - Effect of isokinetic strength-training on functional ability and walking
      efficiency in adolescents with cerebral palsy.
AB  - This study investigated changes in knee extensor and flexor strength of 17 mildly
      involved adolescents with cerebral palsy in response to an eight-week isokinetic
      strength-training program. Peak torque and work were used as strength outcome
      measures. Subsequent changes in gross motor function and walking efficiency were
      evaluated. The significant strength gains of 21 to 25 per cent observed were
      similar in magnitude to those previously reported for able-bodied individuals. A
      significant number of subjects showed an increase in gross motor ability.
      However, walking velocity and walking efficiency were unchanged. Strength gains
      of 15 to 17 per cent were maintained for three months after the cessation of
      isokinetic training.

PMID- 7589860
TI  - Risk factors for the co-occurrence of partial epilepsy, cerebral palsy and mental
      retardation.
AB  - A case-control study (64 cases and 209 controls) was carried out to identify risk
      factors for the co-occurrence of early-onset partial epilepsy, cerebral palsy and
      mental retardation in children with and without cerebral malformations. History
      of epilepsy in first-degree relatives, maternal diseases in the two years before
      pregnancy, placental pathologies, low gestational age, being small for dates,
      neonatal convulsions and the need for cardiopulmonary resuscitation were
      associated with partial epilepsy, cerebral palsy and mental retardation. A family
      history of epilepsy in first-degree relatives was surprisingly frequent in both
      groups, suggesting that genetic factors play an important role for children with
      and without cerebral malformations.

PMID- 7589861
TI  - Myotatic reflex responses of non-disabled children and children with spastic
      cerebral palsy.
AB  - Surface electromyography (EMG) was used to examine lower-extremity myotatic
      reflex responses following patellar or Achilles tendon taps to normally
      developing, non-disabled infants and to individuals with cerebral palsy (CP).
      Reflex irradiation was present in non-disabled infants and infants with CP under
      two years of age. The only significant differences in myotatic reflex responses
      between the two groups at this age was the higher amplitude of the directly
      stimulated muscle of children with CP. After two years the amplitude did not
      differ between groups. Reflex irradiation, however, was greatly reduced in the
      non-disabled children but not in the children with cerebral palsy. These findings
      and those of non-human animal studies indicate the possible neural mechanisms
      that underlie reflex irradiation of individuals with CP. The potential clinical
      relevance of these findings is discussed.

PMID- 7589863
TI  - Inter-observer agreement of the assessment of coma scales and brainstem signs in
      non-traumatic coma.
AB  - The authors evaluated the inter-observer agreement between two experienced
      clinicians examining 19 unconscious children who were not paralysed or
      ventilated. Inter-observer reliability was assessed by proportion of agreement,
      disagreement rate and kappa statistics. Corneal reflexes, pupillary responses to
      light and motor responses were the most reliably elicited. Reduction of the
      number of categories improved inter-observer agreement. Some of the disagreement
      may be attributed to changes in the child's condition during the period of
      assessment. There was more agreement about the five-category 0-IV scale than the
      summated Adelaide (10-category) and Jacobi (13-category) scales. The ability of
      these scales to follow changes in the patient's condition and to predict outcome
      needs to be evaluated in a prospective trial.

PMID- 7589862
TI  - Changes in walking pattern between five and six years of age.
AB  - A study was carried out of the parameters of the ground reaction forces and
      temporal and spatial walking parameters of 62 children aged between five and six
      years. The children were evaluated barefoot, walking freely at normal speed over
      the surface of two platforms. The aims were to establish normal parameters for
      children of this age and to identify any differences existing between these ages.
      Differences were noticeable in the kinetic and temporal and spatial walking
      parameters, indicating that maturation has not yet been completed at these ages.

PMID- 7589865
TI  - In vivo diagnosis of Hallervorden-Spatz disease.
AB  - The authors present the MRI findings of two children with insidious walking
      difficulties, signs of corticospinal tract involvement, and signs and symptoms of
      extrapyramidal dysfunction such as rigidity and generalized dystonia, the latter
      with predominance of oromandibular involvement. In one child, MRI revealed
      prominent hypo-intensity in the globus pallidus and in the substantia nigra on T2
      weighted spin echo images, consistent with iron deposition and thus with previous
      post-mortem findings of Hallervorden-Spatz disease. In the other case, the hypo
      intensity was restricted to the globus pallidus, in which a small area of
      hyperintensity in its internal segment was demonstrated--the so called 'eye-of
      the-tiger' sign. The authors propose that a combination of previously mentioned
      neurological signs with these specific MRI findings is highly suggestive of an in
      vivo diagnosis of the late infantile type of HSD.

PMID- 7589864
TI  - Maturation of electroretinograms and visual evoked potentials in preterm infants.
AB  - Electroretinograms (ERGs) and visual evoked potentials (VEPs) to flash
      stimulation were recorded from 51 infants (gestational age 26 to 42 weeks; post
      conceptional age (PCA) 31 to 47 weeks) to give cross-sectional data on the
      maturation of these responses. Sequential recordings were taken from a separate
      group of 24 preterm infants (gestational age 28 to 33 weeks) to give longitudinal
      data. There was a significant decrease in ERG a-wave latency and increase in a-b
      amplitude with increasing PCA in both groups. For the VEPs there was a
      significant decrease in latency of the early negative component (N1) and the
      major positive component (P2). Comparison between recordings made on preterm
      infants with those from term infants at an equivalent PCA suggested faster
      maturation of VEPs in the extra-uterine environment, but no difference in
      maturation of the ERG.

PMID- 7589866
TI  - Cerebral palsy: a paradigm for developmental disabilities.

PMID- 7589867
TI  - The crux.

PMID- 7589868
TI  - 'Bilateral spastic cerebral palsy--a collaborative study between southwest
      Germany and western Sweden.

PMID- 7589869
TI  - The American Academy for Cerebral Palsy and Developmental Medicine (AACPDM)
      annual meeting. Philadelphia, Pennsylvania, September 28-30, 1995. Abstracts.

PMID- 7589870
TI  - Blunted epinephrine response following exercise in autonomic neuropathy.

PMID- 7589871
TI  - Decreased cerebral blood perfusion in an NIDDM patient with an A-to-G mutation in
      the mitochondrial gene; a possible contribution to cognition deficits in
      diabetes.

PMID- 7589872
TI  - Islet transplantation reverses carcass protein loss in diabetic rats without
      inducing disproportionate fat accumulation.
AB  - The Diabetes Control and Complications Trial demonstrated that intensive insulin
      therapy (IIT) improves many secondary complications of insulin-dependent diabetes
      mellitus. However, weight gain in IIT is associated with increased body fat, and
      no improvement in lean body mass. In the present study we investigated the
      effects of experimental diabetes on changes in body composition and probed the
      benefit of glycaemic control achieved through islet transplantation. Male Wistar
      Furth rats (weight 273 +/- 9 g) made diabetic for 2 weeks with streptozotocin (55
      mg/kg) were infused intraportally with 3265 +/- 692 (150 microns islet equivalent
      units) syngeneic islets of Langerhans. Body composition was evaluated by
      proximate analysis in carcasses of transplant rats (Trans), and also in rats made
      diabetic for 2 or 7 weeks (Db-2, Db-7) and in 2- and 7-week sham controls (Sham
      2, Sham-7). Fed plasma glucose levels were 7.3 +/- 1.1, 28.2 +/- 2.4, 26.8 +/-
      3.9, 7.5 +/- 1.0 and 7.0 +/- 0.1 mm/l, respectively, and neither glucose
      tolerance nor fasting plasma insulin differed between control vs transplant rats
      (p > 0.05). Two weeks of diabetes resulted in a body weight 82% of that of
      controls (240 +/- 5 vs 292 +/- 8 g, p < 0.05) and 5 subsequent weeks of diabetes
      further suppressed growth by an additional 12% (p < 0.05). Five weeks following
      islet transplantation, islet-transplant rats had regained lost weight and were
      not significantly different from control animals (274 +/- 19 vs 291 +/- 21 g, p >
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589874
TI  - Effect of myo-inositol supplementation on the development of renal pathological
      changes in the Cohen diabetic (type 2) rat.
AB  - A lower concentration of intracellular myo-inositol has been implicated in the
      development of diabetic nephropathy. This was based on short-term studies showing
      that early administration of aldose reductase inhibitors or myo-inositol
      supplementation reduces increased glomerular filtration rate and partly reduces
      increased urinary albumin excretion in streptozotocin diabetic rats. We studied
      the effect of long-term (4 months) administration of 1% myo-inositol supplement
      to the Cohen diabetic (type 2) rat on the development of nephropathy and renal
      Na(+)-K(+)-ATPase. This treatment reduced the increased renal Na(+)-K(+)-ATPase
      activity but had no effect on blood glucose levels, body weight, increased kidney
      weight, or creatinine clearance and did not prevent or reduce the development of
      renal glomerular pathology. There was no correlation between the level of Na(+)
      K(+)-ATPase activity and the degree of nephropathy. It is possible that the renal
      pathological changes are due to metabolic and humoral factors resulting from
      hyperglycaemia, other than myo-inositol depletion. The fact that myo-inositol
      treatment had no effect on the development of renal pathological changes but was
      shown to have a beneficial effect on restoring impaired conduction velocity and
      on the disruption of structural elements in the nerve indicates that the effect
      of the biological changes ensuing from hyperglycaemia vary in different tissues
      depending on local conditions.

PMID- 7589873
TI  - Haemodynamic and metabolic effects in diabetic ketoacidosis in rats of treatment
      with sodium bicarbonate or a mixture of sodium bicarbonate and sodium carbonate.
AB  - To examine factors determining the haemodynamic and metabolic responses to
      treatment of diabetic ketoacidosis with alkali, groups of anaesthetised and
      ventilated rats with either diabetic ketoacidosis (mean arterial pH 6.86-6.96,
      mean arterial blood pressure 63-67 mm Hg) or hypovolaemic shock due to blood
      withdrawal (mean pHa 7.25-7.27, mean arterial blood pressure 36-41 mm Hg) were
      treated with sodium chloride ('saline'), sodium bicarbonate or 'Carbicarb'
      (equimolar bicarbonate plus carbonate). In the diabetic ketoacidosis series,
      treatment with either alkali resulted in deterioration of mean arterial blood
      pressure and substantial elevation of blood lactate, despite a significant rise
      in myocardial intracellular pH determined by 31P-magnetic resonance spectroscopy.
      These effects were accompanied by falling trends in the ratios of myocardial
      phosphocreatine and ATP to inorganic phosphate. Erythrocyte 2,3
      bisphosphoglycerate was virtually absent in animals with diabetic ketoacidosis of
      this severity and duration. In contrast, in shock due to blood withdrawal,
      infusion of saline or either alkali was accompanied by a transient elevation of
      mean arterial blood pressure and no significant change in the already elevated
      blood lactate; erythrocyte 2,3-bisphosphoglycerate was normal in these animals.
      The effect of alkalinization in rats with severe diabetic ketoacidosis was
      consistent with myocardial hypoxia, due to the combination of very low initial
      erythrocyte 2,3-bisphosphoglycerate, alkali-exacerbated left shift of the
      haemoglobin-oxygen dissociation curve and artificial ventilation. No evidence was
      found for any beneficial effect of 'Carbicarb' in either series of animals;
      'Carbicarb' and sodium bicarbonate could be deleterious in metabolic acidosis of
      more than short duration.

PMID- 7589875
TI  - Expression of Reg gene in the Syrian golden hamster pancreatic islet regeneration
      model.
AB  - We have reported previously that cellophane wrapping of the hamster pancreas is a
      stimulus that leads to the induction of duct epithelial cell proliferation,
      followed by endocrine cell differentiation and new islet formation. Reg is a
      candidate gene that has been reported to be expressed in regenerating pancreatic
      islets, suggesting a role in islet growth. We examined Reg gene expression in the
      cellophane-wrap model by isolating total RNA from hamster pancreata at various
      times after wrapping. Northern blot analysis using a rat cDNA Reg probe showed no
      expression of Reg in control non-wrapped hamster pancreas, whereas a strong
      signal was detected in control wrapped rat pancreas. Using reverse transcription
      of RNA followed by polymerase chain reaction (PCR) we amplified, isolated and
      sequenced a 194 base pair product which showed homology to rat Reg in both
      control and wrapped hamster pancreas. When the PCR product was used as a probe
      for Northern blot analysis, no signal was detected in control non-wrapped
      pancreata. In contrast, a strong signal was detected 1 and 2 days after wrapping,
      which then returned to basal between 4 and 6 days after wrapping. A similar
      temporal pattern was observed using in situ hybridization to localize the Reg
      gene. One- and 2-day wrapped but not control pancreas expressed Reg in acinar
      cells, but not in islets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589877
TI  - Islet transplantation in diabetic rats normalizes basal and exercise-induced
      energy metabolism.
AB  - Transplantation of islets of Langerhans in diabetic rats normalizes resting
      glucose and insulin levels, but it remains unclear whether islet transplantation
      restores resting and exercise-induced energy metabolism. Therefore, we compared
      energy metabolism in islet transplanted rats with energy metabolism in normal
      controls and in streptozotocin-induced diabetic rats. Indirect calorimetry was
      applied before, during, and after moderate swimming exercise. Blood was sampled
      by means of a heart catheter for determination of nutrient and hormone
      concentrations. In islet transplanted rats, the results from indirect calorimetry
      and the nutrient and hormone concentrations were similar to the results in normal
      controls. In resting diabetic rats, insulin levels were very low, while glucose
      levels were exaggerated. Compared to resting controls, fat oxidation and energy
      expenditure were elevated, but carbohydrate oxidation was similar. Exercise
      increased energy expenditure and was similar in diabetic and control rats.
      Carbohydrate oxidation was lower and fat oxidation was higher in diabetic than in
      control rats. Exercise-induced increments in glucose, lactate and non-esterified
      fatty acid levels were the highest in diabetic rats. Thus, at rest, but not
      during exercise, insulin influences energy expenditure. Insulin reduces lipolysis
      and glycogenolysis. It enhances the relative contribution of carbohydrate
      oxidation and reduces fat oxidation to total energy expenditure, at rest and
      during exercise. Absence of insulin enhances anaerobic glycolytic pathways during
      exercise. It is concluded that in diabetic rats, islet transplantation of 50% of
      the normal pancreatic endocrine volume successfully normalizes insulin levels and
      hence energy metabolism at rest and during exercise.

PMID- 7589876
TI  - Effect of cilostazol on experimental diabetic neuropathy in the rat.
AB  - Two proposed mechanisms of diabetic neuropathy are microvascular ischaemia and a
      reduction in Na,K-ATPase activity. We evaluated the effect of cilostazol, a drug
      that is both a potent phosphodiesterase inhibitor that normalizes nerve Na,K-AT
      Pase and a vasodilator, on nerve blood flow (NBF) to determine whether it would
      improve experimental diabetic neuropathy. We examined whether epineurally applied
      cilostazol acted as a vasodilator on the peripheral nerve of normal and diabetic
      rats, and whether feeding the rats a cilostazol-supplemented diet could improve
      diabetic neuropathy. Cilostazol increased nerve blood flow (NBF) in a dose
      dependent fashion with an EC50 of 10(-5.74) mol/l. Cilostazol also normalized NBF
      in experimental diabetic neuropathy with a 10(-4) mol/l local application on the
      sciatic nerve. In diabetic neuropathy, a cilostazol-supplemented diet improved
      both NBF and nerve conduction in a dose- and time-dependent fashion. Potential
      mechanisms of action of cilostazol on the nerve include its effect on NBF, Na, K
      ATPase, and restoration of the thromboxane:prostacyclin ratio. Cilostazol may
      have potential in the treatment of diabetic neuropathy.

PMID- 7589878
TI  - Insulin-like growth factor-II gene expression in a rat insulin-producing beta
      cell line (INS-1) is regulated by glucose.
AB  - A highly differentiated rat glucose-responsive insulin producing cell line INS-1
      expresses high levels of insulin-like growth factor-II (IGF-II). Basal levels of
      IGF-II gene mRNA were expressed in cells cultured at 1-6 mmol/l glucose. At
      glucose concentrations of 10-20 mmol/l, IGF-II mRNA was increased more than
      threefold after 44 h of incubation. Levels of IGF-II mRNA in INS-1 cells
      incubated at 5.6 and 20 mmol/l glucose in the presence of 4 micrograms/ml
      actinomycin D are comparable and are not reduced during 20 h of treatment,
      indicating the high stability of IGF-II mRNA in this cell line. From the three
      rat IGF-II promoters, promoter 3 is by far the most active in INS-1 cells. The
      IGF-II promoter 3 activity and IGF-II mRNA production at high glucose
      concentrations increased threefold over their respective levels at low glucose
      concentration, suggesting that the glucose-induced IGF-II gene expression in this
      beta-cell line might be transcriptionally controlled. The up-regulation of IGF-II
      mRNA by glucose was not due to the increased intracellular cyclic AMP levels or
      protein kinase C activation. A protein kinase C activator had no effect on IGF-II
      gene expression, and an adenylate cyclase activator (forskolin), suppressed the
      stimulatory effects of glucose on the IGF-II mRNA. Under all the experimental
      conditions examined, the IGF-II and insulin genes were differentially regulated
      in INS-1 cells. The IGF-II gene expression and DNA synthesis, however, were
      regulated in parallel, suggesting that these two cellular activities are closely
      associated.

PMID- 7589879
TI  - Insulin increases cyclic nucleotide content in human vascular smooth muscle
      cells: a mechanism potentially involved in insulin-induced modulation of vascular
      tone.
AB  - It has been suggested that insulin exerts a vasodilating effect, but the
      mechanisms involved are not completely understood. Since cyclic nucleotides
      mediate the vasodilation induced by endogenous substances, such as prostacyclin
      and nitric oxide, we aimed to investigate the influence of insulin (concentration
      range 240-960 pmol/l) on both cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP) content in human vascular smooth muscle cells.
      Insulin dose-dependently increased both nucleotides (cAMP: from 0.7 +/- 0.1 to
      2.6 +/- 0.4 pmol/10(6) cells, p = 0.0001; cGMP: from 1.3 +/- 0.2 to 3.4 +/- 0.7
      pmol/10(6) cells, p = 0.033). This increase is receptor-mediated, since it was
      blunted when cells were preincubated with the tyrosine kinase inhibitor
      genistein. The effect of insulin remained significant (p = 0.0001) when
      preincubation with the phosphodiesterase inhibitor theophylline prevented cyclic
      nucleotide catabolism. The increase of cGMP was blunted when the cells were
      preincubated with the guanylate cyclase inhibitor methylene blue, and with the
      nitric oxide-synthase inhibitor NG-monomethyl-L-arginine. At all the
      concentrations tested, insulin potentiated the increase of cAMP induced by the
      stable prostacyclin analogue Iloprost (p = 0.0001), whereas only at 1920 pmol/l
      did it potentiate the cGMP increase induced by glyceryltrinitrate (p = 0.05).
      This study demonstrates that the vasodilating effects exerted by insulin may at
      least in part be attributable to an increase of both cGMP and cAMP via a receptor
      mediated activation of adenylate and guanylate cyclases in human vascular smooth
      muscle cells and that the insulin effect on cGMP is mediated by nitric oxide.

PMID- 7589880
TI  - HepG2/erythrocyte glucose transporter (GLUT1) gene in NIDDM: a population
      association study and molecular scanning in Japanese subjects.
AB  - To evaluate the role of mutations in the glucose transporter (GLUT1) gene in
      Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM), we first
      conducted a population association study using the XbaI polymorphism of the gene.
      A polymerase chain reaction (PCR)-based assay was developed and used for the
      analysis. When analysed in 91 diabetic patients and 87 non-diabetic control
      subjects, the distribution of the genotype frequency was significantly different
      between the two groups (p = 0.0025). The (-) allele was significantly associated
      with NIDDM (odds ratio 2.317, 95% confidence interval 1.425-3.768). To identify
      possible mutation(s) in the GLUT1 gene, which was in linkage disequilibrium with
      the (-) allele, all ten exons of the gene were analysed by PCR single-strand
      conformation polymorphism (SSCP) analysis in 53 diabetic patients with at least
      one (-) allele. Variant SSCP patterns were detected in exons 2, 4, 5, 7, 9 and
      10. Sequence analysis revealed that all the variants represented silent
      mutations. One of the variants in exon 2, GCT (Ala15)-->GCC(Ala), created a
      HaeIII restriction site. This polymorphism was common in Japanese subjects with
      heterozygosity of 0.36 and polymorphism information content 0.29. We conclude
      that the structural mutation of GLUT1 is rare and not likely to be a major
      genetic determinant of NIDDM in Japanese subjects. The XbaI (-) allele of the
      GLUT1 gene appeared to be a genetic marker of NIDDM in Japanese subjects. The
      possibility of the presence of mutation(s) in the regulatory region of the gene
      or in another locus nearby could not be excluded.

PMID- 7589882
TI  - Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from
      newly-diagnosed IDDM patients.
AB  - The bcl-2 gene product has been shown to regulate apoptotic cell death, and its
      dysregulation has been shown to induce several abnormalities in the immune
      system. No data exist regarding bcl-2 expression in autoimmune diseases, such as
      human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein
      expression by testing T lymphocytes from 15 newly-diagnosed (< 3 weeks) IDDM
      patients in comparison to 10 age-matched control subjects. The expression of bcl
      2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by
      two- or three-colour immunofluorescence. When the percentage and mean
      fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals and
      patients were compared, we found that bcl-2 expression within the CD3+ and CD4+
      CD45R0+ T-cell populations was reduced significantly in IDDM patients (46.8 +/-
      15.4 vs 79.6 +/- 11.7; 25.7 +/- 3.8 vs 47.15 +/- 5.7, respectively; p < 0.001).
      To establish whether low bcl-2 expression in T cells from newly-diagnosed
      patients reflects their susceptibility to death by an apoptotic process, we also
      evaluated DNA staining with propidium iodide in CD3+ lymphocyte suspension after
      a (24-72 h) culture period (spontaneous apoptosis). We found that IDDM patients
      have higher levels of spontaneous apoptosis (mean +/- SEM: 24 h = 4.6 +/- 0.8; 48
      h = 9.9 +/- 1; 72 h = 12.8 +/- 1.1) than control subjects (24 h = 1.8 +/- 0.4; 48
      h = 4.6 +/- 0.4; 72 h = 5.7 +/- 0.3; p < 0.02-0.001). Our study suggests that
      recent onset IDDM is characterised by reduced bcl-2 expression, which in turn may
      be associated with the increased spontaneous apoptosis we observed.

PMID- 7589881
TI  - UK prospective diabetes study (UKPDS) 14: association of angiotensin-converting
      enzyme insertion/deletion polymorphism with myocardial infarction in NIDDM.
AB  - The deletion allele of the insertion/deletion polymorphism of the angiotensin
      converting enzyme gene has been suggested to be an independent risk factor for
      myocardial infarction, particularly in subjects judged to be "low-risk" by the
      criteria of lipid status and body mass index. In a prospective, matched case
      control study, we have investigated the role of this polymorphism as a risk
      factor for myocardial infarction in 173 newly-diagnosed British Caucasian non
      insulin-dependent diabetic subjects taken from the United Kingdom Prospective
      Diabetes Study who subsequently developed myocardial infarction and 297 control
      subjects from the same study population matched for known cardiovascular risk
      factors including age at diagnosis of diabetes, gender, blood pressure, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol,
      triglyceride and smoking habit. A trend towards increased risk conferred by
      homozygosity for the deletion allele was observed in cases (odds ratio 1.63, p =
      0.09). When the population was stratified according to the matched risk factors,
      the deletion allele was associated with myocardial infarction in those with low
      plasma low-density lipoprotein cholesterol (odds ratio 3.67, p = 0.002), or low
      triglyceride (odds ratio 3.14, p = 0.005). The strongest association of the
      deletion allele with myocardial infarction was observed in subjects with both low
      low-density lipoprotein cholesterol and low triglyceride levels (odds ratio 9.0,
      p < 0.001). These results show that the deletion allele is a risk factor for
      myocardial infarction in non-insulin-dependent diabetic patients who have a
      favourable lipid profile.

PMID- 7589885
TI  - Evidence for importance of gender and birth cohort for risk of IDDM in offspring
      of IDDM parents.
AB  - The risk of developing diabetes is higher in offspring of fathers than of mothers
      with insulin-dependent diabetes mellitus (IDDM). The reasons for this sex
      differential are unclear, as early studies were often selected and relatively
      small. We conducted a prospective study on the risk of IDDM in a cohort of 9,453
      offspring from 5,255 Finnish parents with diabetes diagnosed before age 30 years.
      Age of first admission to the hospital was considered to be the age of diagnosis
      of IDDM in the offspring; IDDM occurred in 248 offspring. The risk of IDDM tended
      to be lower in the offspring of the same gender as the diabetic parent (adjusted
      risk ratio (RR) 0.78; p = 0.50). When offspring were of same gender as the
      diabetic parent, male offspring had a higher risk of IDDM than female offspring
      (RR 2.28; 95% confidence interval 1.53-3.38), whereas if the gender of the
      diabetic parent and the offspring were different, the risk in male offspring was
      lower (RR 0.43; 95% confidence interval 0.31-0.62). For the offspring of diabetic
      fathers, the cumulative risk by the age of 20 was higher (7.6%) than for those
      with diabetic mothers (3.5%) (p < 0.0001). In a multivariate analysis
      statistically significant predictors of IDDM in the offspring were the sex of the
      parent, the year of birth and the birth order of the offspring. The risk of IDDM
      in the offspring increased by 9% per year of birth cohort. By age 20, the
      cumulative risk of developing IDDM in the offspring of diabetic parents was 5.3%,
      10 times higher than in the background population. It is likely that genetic
      factors seem to have played a major role in the continuous increase of IDDM
      incidence in Finnish children.

PMID- 7589883
TI  - Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100
      in NIDDM.
AB  - We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein
      B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry
      method in six patients with non-insulin-dependent diabetes mellitus (NIDDM) (four
      males, two females, age 57.5 +/- 2.2 years (mean +/- SEM), weight 88.2 +/- 5.5
      kg, glycated haemoglobin (HbA1) 8.5 +/- 0.5%, plasma total cholesterol
      concentration 5.7 +/- 0.5 mmol/l, triglyceride 3.8 +/- 0.9 mmol/l, high-density
      lipoprotein (HDL) cholesterol 1.0 +/- 0.1 mmol/l) and six non-diabetic subjects
      matched for age, sex and weight (four males, two females, age 55.7 +/- 2.8 years,
      weight 85.8 +/- 5.6 kg, HbA1 6.5 +/- 0.1%, plasma total cholesterol concentration
      5.7 +/- 0.5 mmol/l, triglyceride 1.2 +/- 0.1 mmol/l, HDL cholesterol 1.4 +/- 0.1
      mmol/l). HbA1, plasma triglyceride and mevalonic acid (an index of cholesterol
      synthesis in vivo) concentrations were significantly higher in the diabetic
      patients than in the non-diabetic subjects (p = 0.006, p = 0.02 and p = 0.004,
      respectively). VLDL apoB absolute secretion rate was significantly higher in the
      diabetic patients compared with the non-diabetic subjects (2297 +/- 491 vs 921 +/
      115 mg/day, p < 0.05), but there was no significant difference in the fractional
      catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB
      secretion rate and (i) fasting C-peptide (r = 0.84, p = 0.04) and (ii) mevalonic
      acid concentration (r = 0.83, p < 0.05) in the diabetic patients but not in the
      non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589884
TI  - HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional
      contribution to disease risk by the TAP2 locus.
AB  - The TAP2 gene, located in the HLA class II region, encodes a subunit of a
      transporter involved in the endogenous antigen-processing pathway, and has been
      suggested to contribute to the genetic risk for insulin-dependent diabetes
      (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred
      by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands,
      their first degree relatives, and in 62 normal control subjects. A decreased
      frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in
      control subjects, pc < 0.05). Analysis of 73 informative meiotic events in IDDM
      and control families demonstrated a recombination fraction between HLA DQB1 and
      TAP2 loci of 0.041 (Log of the odds score = 16.5; p < 10(-8)) indicating strong
      linkage between these loci. Family haplotype analysis demonstrated linkage
      disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced
      frequency of TAP2B was associated with its absence on the IDDM susceptible
      DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the
      association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent
      in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in
      IDDM families showed a slight but not significant decrease in TAP2B allele
      frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501
      DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated
      DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele
      frequency (4%) similar to that in IDDM haplotypes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7589886
TI  - A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the
      association with diabetes mellitus.
AB  - A possible pathogenic mutation in the glucagon receptor gene causing a Gly to Ser
      change at codon 40 (Gly40Ser) was reported to be associated and linked with non
      insulin-dependent diabetes mellitus (NIDDM), in France and Sardinia. Since the
      frequency of the mutation (Gly40Ser), about 5% in the French population of
      familial NIDDM and 8% in randomly chosen diabetic patients in Sardinia, was much
      higher than that of any of the previously reported mutations in candidate genes,
      it is important to clarify whether the contribution of this mutation to NIDDM is
      universal. In this study, we investigated the association of this mutation with
      diabetes mellitus in a large number of Japanese diabetic patients (383 NIDDM and
      53 insulin-dependent diabetic patients) by polymerase chain reaction-restriction
      fragment length polymorphism analysis. None of the Japanese diabetic patients
      showed Gly40Ser mutation and the association of this mutation with NIDDM was
      significantly different (p < 4.10(-5) vs French, p < 3.10(-6) vs Sardinian by
      Fisher's exact test). The results not only indicate that the mutation plays
      little, if any, role in susceptibility to diabetes in Japan, but also indicate
      the genetic heterogeneity in NIDDM and further emphasize the importance of
      studies on genetic susceptibility to NIDDM and other complex traits in different
      ethnic groups.

PMID- 7589887
TI  - The pathogenesis of NIDDM: the role of the pancreatic beta cell.

PMID- 7589888
TI  - Insulin deficiency and insulin resistance in the pathogenesis of NIDDM: is a
      divorce possible?

PMID- 7589889
TI  - Insulin, corticosterone and the autonomic nervous system in animal obesities: a
      viewpoint.

PMID- 7589891
TI  - The non-receptor tyrosine kinase Lyn is localised in the developing murine blood
      brain barrier.
AB  - The blood-brain barrier, formed by brain endothelium, is critical for brain
      function. The development of the blood-brain barrier involves brain angiogenesis
      and endothelial cell differentiation, processes which require active signal
      transduction pathways. The differentiation of brain endothelial cells to the
      "blood-brain-barrier phenotype" involves cytoskeletal changes which modulate the
      tightness of the barrier. In order to identify signal transduction proteins
      involved in blood-brain barrier development, cDNA from bovine and murine brain
      endothelial cells was used in a polymerase chain reaction for cloning of DNA
      encoding Src homology 3 domains. Src homology 3 domains are structural domains
      found in many signal transduction proteins. These domains often mediate
      interaction of signaling proteins with the cytoskeleton and therefore may play a
      role in the regulation of the cytoskeletal changes which occur during blood-brain
      barrier development. Unexpectedly, all bovine and murine clones analyzed from
      polymerase chain reactions encoded the Src homology 3 domain of one protein,
      namely the non-receptor tyrosine kinase, Lyn, which is involved in signal
      transduction in cells of the hemopoietic system. In situ hybridization analyses
      confirmed the presence of lyn mRNA in developing blood vessels in embryonic and
      early post-natal mouse brain, but not in endothelium outside the brain. In bovine
      brain endothelial cells in primary culture, p53lyn is highly abundant and present
      in two forms which have different patterns of tyrosine phosphorylation. These
      data suggest that Lyn may be involved in transduction of growth and
      differentiation signals required for blood-brain-barrier development.

PMID- 7589890
TI  - The spatial and temporal expression of the alpha 2 beta 1 integrin and its
      ligands, collagen I, collagen IV, and laminin, suggest important roles in mouse
      mammary morphogenesis.
AB  - To begin to determine the role of the alpha 2 beta 1 integrin and its ligands,
      collagen I, collagen IV, and laminin, in mammary epithelial differentiation in
      vivo, we determined the expression of these molecules by in situ hybridization
      and immunofluorescence in the developing mouse mammary gland. Expression of
      collagen I, collagen IV, and laminin mRNAs in the mammary gland during puberty
      corresponded to the period of greatest growth of the gland, 4-7 weeks
      postnatally. Collagen I expression preceded collagen IV expression, both of which
      preceded laminin expression, suggesting an important temporal sequence of
      extracellular matrix (ECM) production. When growth of the epithelium ceased in
      the adult virgin gland, expression of all three mRNAs became undetectable.
      Following the onset of pregnancy these molecules were re-expressed with the same
      chronology observed during puberty. Collagen I, collagen IV, and laminin were
      expressed by stromal cells immediately surrounding the developing ductal
      epithelium. Surprisingly, we found no expression of ECM components in the
      epithelial cells, suggesting the mammary epithelium does not synthesize its own
      basement membrane. The distribution of collagen I was consistent with a role in
      duct formation, since collagen I was strikingly abundant around larger mammary
      ducts, but was sparse around growing endbuds or alveoli. Conversely, there was
      abundant laminin near growing endbuds and around alveoli, and less around large
      ducts, suggesting its role is different than collagen I. The alpha 2 beta 1
      integrin was present on the basal, lateral, and apical surfaces of the mammary
      epithelium throughout postnatal development and pregnancy. The alpha 2 beta 1
      integrin expression was strongest at midpregnancy, suggesting a role for alpha 2
      beta 1 integrin in the alveolar formation that occurs at this time. The alpha 2
      beta 1 integrin expression decreased dramatically in the lactating gland. Our
      results suggest that alpha 2 beta 1 integrin interactions with its temporally and
      spatially regulated ligands, collagen I, collagen IV, and laminin, could play an
      important role in mammary morphogenesis in vivo.

PMID- 7589892
TI  - Formation of cartilage-like spheroids by micromass cultures of murine C3H10T1/2
      cells upon treatment with transforming growth factor-beta 1.
AB  - Formation of cartilage during both embryonic development and repair processes
      involves the differentiation of multipotential mesenchymal cells. The mouse cell
      line, C3H10T1/2, has been shown to be multipotential and capable of
      differentiating into various phenotypes normally derived from embryonic mesoderm,
      including myocytes, adipocytes and chondrocytes. In this study, we have analyzed
      the induction of chrondrogenesis in C3H10T1/2 cells by transforming growth factor
      beta (TGF-beta 1, human recombinant form). Treatment of high-density micromass
      cultures of C3H10T1/2 cells with TGF-beta 1 resulted in the formation of a three
      dimensional spheroid structure, which exhibited cartilage-like histology.
      Extracellular matrix components characteristic of cartilage, type II collagen and
      cartilage link protein, were demonstrated by immunohistochemistry. TGF-beta 1
      treatment increased collagen synthesis, and immunoblot analysis showed the
      presence of type II collagen in TGF-beta 1-treated micromass cultures, but not in
      TGF-beta 1-treated monolayer cultures nor in untreated cultures. An increase in
      radioactive sulfate uptake relative to DNA synthesis was also seen in TGF-beta 1
      treated micromass cultures forming spheroids, indicating the increased synthesis
      of sulfated proteoglycans. These observations indicated that the spheroids formed
      are of a cartilaginous nature, and that multipotential C3H10T1/2 cells, which do
      not spontaneously enter the chondrogenic pathway, can be induced to undergo
      cellular differentiation towards chondrogenesis in vitro through culture in a
      favorable environment.

PMID- 7589893
TI  - Evidence for a terminal differentiation process in the rat liver.
AB  - In rapidly renewing epithelia, such as skin and gut, as well as hemopoietic cells
      and stromal fibroblasts, the process of progenitor cell maturation, terminal
      differentiation and senescence from cells of a fetal phenotype is strikingly
      similar. To examine hepatocellular maturation, we studied embryonic, suckling and
      young adult rat liver cells with multiparametric fluorescence activated cell
      sorting (FACS), after exclusion of hemopoietic, endothelial, Kupffer, and
      nonviable cells. With maturation, cell granularity and autofluorescence
      exponentially increased from fetal liver to suckling and adult liver as the
      proportion of S phase cells progressively declined from 33.8% +/- 1.3% to 4.9% +/
      2.8% and 1.1% +/- 0.6% (P < 0.05), respectively. In liver from fetal and
      suckling rats, all hepatocytes were mononuclear and contained diploid DNA whereas
      21.2% +/- 5.9% hepatocytes in adult liver were binucleated. Analysis of nuclear
      DNA content in adult hepatocytes demonstrated that 53.3% +/- 3.9% of the nuclei
      were diploid, 43.6% +/- 3.5% tetraploid and 0.5 +/- 0.6% octaploid. However, in
      the adult liver, small, mononuclear cells were also present with granularity and
      autofluorescence comparable to fetal hepatoblasts, as well as glucose-6
      phosphatase activity, diploid DNA in 89.0% +/- 2.1% of the nuclei, and with
      increased granularity in culture. Since general features of terminal cellularity
      differentiation and senescence include cessation of mitotic activity, polyploidy
      and accumulation of autofluorescent secondary lysosomes, our data suggest that
      liver cells too undergo a process of terminal differentiation.

PMID- 7589894
TI  - Changes in the expression of intermediate filaments and desmoplakins during
      development of human notochord.
AB  - Indirect immunofluorescence was used to study the expression of desmosomal and
      intermediate filament (IF) proteins in the human notochord between the 4th and
      12th weeks of embryonic development. Towards the end of this period, the
      development of the notochord is characterized by its gradual physiological
      atrophy and disappearance inside the vertebral bodies. In all of our embryos, the
      notochord cells expressed cytokeratin and vimentin but not desmin, neurofilament
      protein or glial fibrillary acidic protein. Throughout the stages studied, the
      expression of cytokeratin was strong. Vimentin expression, on the other hand,
      changed during the stages studied. In our youngest embryos, vimentin could be
      detected only in the peripheral cells of the notochord. During development, a
      distinct increase occurred in vimentin expression, and in the oldest embryos, all
      notochord cells showed bright vimentin-specific fluorescence. Simultaneously with
      this modification, a change occurred in the expression of desmosomal proteins:
      The notochord cells expressed desmoplakins abundantly during early stages, but
      weakly or not at all during later stages. Correspondingly, electron microscopy of
      the same stages showed a striking decrease in the number of desmosomes between
      notochord cells. Our results confirm that, during early development, the
      notochord displays features specific for epithelial cells. This accords with the
      view that notochord is of epithelial origin. The modifications observed in the
      expression of IF and desmosomal proteins were temporally correlated with
      developmentally regulated atrophy of the notochord. The programmed regression of
      the notochord cells is thus associated with a switch from a predominantly
      epithelial phenotype to a more mesenchymal one.

PMID- 7589895
TI  - Liver fructose-1,6-bisphosphatase cDNA: trans-complementation of fission yeast
      and characterization of two human transcripts.
AB  - The SV40 early promoter is active both in mammalian cells and in the fission
      yeast Schizosaccharomyces pombe, and is used to drive full-length cDNA in
      polyvalent pcD-libraries. Two such liver libraries, of human and rat origin, were
      used to trans-complement a S. pombe mutant deficient in fructose-1,6
      bisphosphatase (Fru-1,6-Pase) activity, a key gluconeogenic enzyme restricted to
      liver, kidney and intestine in mammals. A rat liver Fru-1,6-Pase cDNA was readily
      cloned and sequenced. Complementary PCR experiments revealed full-length Fru-1,6
      Pase cDNA also present in the human liver library, however at a low abundance.
      Two human liver transcripts were thus characterized. Contrary to expectation,
      they were not differentially spliced products. They both encoded the same protein
      and were generated by a polyadenylation choice mechanism. The longest transcript
      comprised two polyadenylation signals and a consensus GT-rich element for the 3'
      processing of the upstream site. Rapid amplification of cDNA ends-polymerase
      chain reaction (RACE-PCR) analysis of 3' ends from hepatic, renal and intestinal
      mRNA disclosed that both Fru-1,6-Pase transcripts are expressed in the three main
      gluconeogenic cell types and are subject to insulin differential modulation. On
      the other hand, overcoming liver cell heterogeneity problems, sequence analysis
      of 16 independent clones of 3' end-cDNA demonstrated that, in addition to a
      monocytic type corresponding to a previously described lambda gt11 clone, human
      liver does not contain a hepatic type Fru-1,6-Pase comprising a liver-specific
      carboxyl-terminal extension like its rat counterpart. This liver-specific
      extension is involved in enzyme up-regulation and appears to give a conclusive
      advantage to the rat hepatic enzyme over the human one when trans-complementing
      mutant yeast.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589896
TI  - Enhanced potency of 9-cis versus all-trans-retinoic acid to induce the
      differentiation of human neuroblastoma cells.
AB  - All-trans-retinoic acid (ATRA) has been shown to be one of the most potent
      chemical inducers of human neuroblastoma differentiation. The recent discovery
      that the stereoisomer of ATRA, 9-cis-retinoic acid (9-cis-RA), binds to both the
      retinoic acid and retinoid X series of receptors prompted us to evaluate the
      ability of this compound to promote differentiation of this cell type. Using the
      LA-N-5 cell line, we have now determined that 9-cis-RA can induce the
      differentiation of human neuroblastoma cells as evidenced by dose-dependent
      inhibition of cell proliferation, neurite outgrowth, increased
      acetylcholinesterase activity, and reduction of N-myc mRNA expression. In
      comparing the effects of 9-cis-RA to ATRA, we found that while both compounds
      induced qualitatively similar cholinergic (versus adrenergic) features in LA-N-5
      cells, 9-cis-RA was 5-to-10-fold more potent than ATRA in its antiproliferative
      and differentiation activity. These results were supported by transient
      transfection experiments utilizing chloramphenicol acetyltransferase (CAT)
      plasmid constructs containing a retinoic acid responsive regulatory element which
      showed a 2-to-3-fold increase in reporter gene activity induced with 9-cis-RA
      over that seen with ATRA at pharmacologically relevant retinoid concentrations (>
      10(-8) M). Furthermore, we have determined that 9-cis-RA can significantly
      enhance mRNA levels of the nuclear retinoic acid receptors alpha and beta in LA-N
      5 cells. Taken together, these findings have established the ability of 9-cis-RA
      to induce neuroblastoma differentiation and suggest that this retinoic acid
      isomer may have better therapeutic characteristics than ATRA.

PMID- 7589897
TI  - Ontogeny of the alloimmune response against a transplanted tumor in Xenopus
      laevis.
AB  - Xenopus laevis lymphoid tumor cells of the ff genotype grow after transplantation
      in inbred ff tadpoles or young post-metamorphic animals, but do not grow in fully
      grown ff adults. The ability to grow is lost progressively after metamorphosis
      and is apparently due to an immune response of the adult host against minor
      histocompatibility antigens (non-MHC encoded) expressed by the tumor cells. The
      difference in alloimmune responses between the larval and the adult immune system
      of the amphibian Xenopus has been subsequently investigated with this new in vivo
      model. The resistance of the host against transplanted tumor cells rises during
      the post-metamorphic development in parallel with the second histogenesis
      observed in the thymus, the expression of MHC class II by peripheral T cells and
      the recovery of T cell effector functions such as MLR, and can be abrogated by
      sub-lethal irradiation. Pre-immunization of ff adults with irradiated ff-2 cells
      specifically accelerates subsequent ff skin graft rejection, which implies the
      generation of memory against antigenic determinants common between the ff skin
      and the tumor cells. Similarly, both anti-ff alloserum and anti-ff-2 serum
      contain antibodies specifically precipitating two surface proteins (180-200 kDa)
      from ff-2 cells. One of these proteins is also detected on normal ff thymocytes
      and splenic T cells. On the other hands, ff-2 tumor cells (MHC I+II-) are not
      rejected by class I-negative tadpoles (class I expression on the tumor cell
      surface is even increased), and no anti-tumor antibody response can be detected.
      However, tumor growth has been reduced in tadpoles following priming with
      irradiated ff-2 cells, although immunization is not sufficient to prevent
      ultimate tumor development and tadpole death. Moreover, priming with irradiated
      ff-2 cells at larval stages does interfere with tumor growth in transplanted
      young post-metamorphic adults, suggesting that long-lived memory has been
      generated and has been maintained through metamorphosis. These results suggest
      that the lack of tumor rejection by larvae results from an incomplete effector
      function rather than an absence of recognition. Full responsiveness against minor
      H antigens cannot be elicited before adulthood.

PMID- 7589898
TI  - Inhibition of proliferation in 8-week-old mdx mouse muscle fibroblasts in vitro.
AB  - Our purpose is to understand why mdx muscle does not show the progressive
      degeneration observed in human Duchenne muscular dystrophy (DMD) muscle. In the
      mouse, the regenerative process compensates for the necrosis of the muscle
      fibers, particularly during the acute phase of the disease (5-9 weeks). In DMD
      muscle, there is a gradual failure of the regenerative process and the muscle
      fibers are replaced by connective and fatty tissue. We propose that distinct
      properties of mdx and DMD muscle fibroblasts could be one of the reasons for the
      differences between the mdx and DMD phenotypes. We found that fibroblasts taken
      from human DMD and control muscle had similar in vitro proliferative capacities.
      The proliferation rate of mouse muscle fibroblasts decreased during the acute
      phase of the disease, and inhibition was complete in fibroblasts from 8-week-old
      mdx mice. Moreover, the medium conditioned by these cells inhibited fibroblast
      proliferation. The effect was specific for fibroblasts, since this conditioned
      medium stimulated myoblast proliferation, as did control fibroblast-conditioned
      medium. These results suggest that 8-week-old mdx mouse muscle fibroblasts
      produce an inhibitor of their own proliferation and a growth factor specific for
      myoblasts in vitro. If these factors are secreted in vivo, the growth inhibitory
      factory may stop fibroblast proliferation whereas the mitogenic activity could
      stimulate satellite cell proliferation, thus favouring muscle regeneration.

PMID- 7589899
TI  - Keratin 18 is associated with a subset of older taste cells in the rat.
AB  - All or nearly all intragemmal (elongated) cells of rat taste buds were
      immunopositive for keratins 7, 8, and 19. In contrast, keratin 18 was detected in
      19 +/- 5 cells per taste bud (mean +/- sd), or about 25% of the intragemmal
      cells. During taste bud development keratins 7, 8, and 19 were evident initially
      in polygonal cells and later in elongated taste cells. Keratin 8 appeared in
      vallate taste cells at P0 (postnatal day 0), followed by keratins 7 and 19 at P1,
      and keratin 18 at P2-P3. Keratin 18 was always limited to elongated cells. The
      assemblage of elongated taste cells comprising a taste bud began with a single
      elongated cell, rather than with the synchronous elongation of a cluster of
      cells. Developmental errors were observed at P2-P3, e.g., some vallate taste
      cells had a misoriented axis. In order to study the pace of keratin
      differentiation during cell turnover we injected bromodeoxyuridine (BrdU) into
      adult rats to monitor taste cell age. Keratin-19-positive intragemmal cells
      differentiated within 1 day. In contrast, keratin 18 was first detected in cells
      aged 3 days. Hence, both in taste cell development and replacement, keratin 18
      was restricted to the older cells; it was the last taste cell keratin to become
      expressed during differentiation.

PMID- 7589900
TI  - Distribution and developmental changes in vasopressin V2 receptor mRNA in rat
      brain.
AB  - The extrarenal presence of vasopressin V2 receptors (V2Rs) has been suggested but
      never been demonstrated. We investigated the distribution of V2R mRNA expression
      in the brain of newborn and adult rats using the reverse transcription-polymerase
      chain reaction (RT-PCR) and in situ hybridization (ISH). RT-PCR assay revealed
      V2R mRNA in the cerebellum of both newborn and adult rats, and in the cerebrum of
      newborn but not adult rats. Further examination of the newborn rat brain by ISH
      showed dense localization of that V2R mRNA in the choroid plexus, and the neurons
      of the hippocampus and granular layer of the cerebellum. Epithelial cells and
      vascular endothelial cells were strongly stained in the choroid plexus. Moreover,
      expression of V2R mRNA in the hippocampus of the newborn rat decreased with age
      and could not be detected in rats more than 2 weeks old, while in the cerebellum
      V2R mRNA expression was stable and did not change with development. The results
      of our study have demonstrated the presence and distribution of V2R in the brain
      for the first time, and also show that expression of V2R mRNA in the hippocampus
      changes dynamically during the process of development. V2R may play an important
      role in the development of the central nervous system.

PMID- 7589901
TI  - Conditional inhibition of erythroid differentiation by c-Myb/oestrogen receptor
      fusion proteins.
AB  - The c-myb proto-oncogene encodes a transcription factor that has been implicated
      in the regulation of haemopoietic cell differentiation and appears also to be
      required for cell proliferation in a number of different lineages. Typically,
      transcription of c-myb is down-regulated during haemopoietic cell
      differentiation, and it has been found in several erythroid and myeloid cell
      lines that constitutive c-myb expression, from a transfected plasmid, blocks this
      differentiation process. To investigate further the activity of c-myb in
      haemopoietic cell differentiation, we have transfected Friend murine
      erythroleukaemia (F-MEL) cells with plasmids encoding conditionally active c
      Myb/oestrogen receptor (Myb/ER) fusion proteins. Transcriptional activity of the
      Myb/ER fusion proteins was found to be strictly hormone-dependent, and this
      property was correlated with the ability of these proteins to inhibit erythroid
      differentiation. From analysis of a Myb/ER protein that lacks the c-Myb
      transactivation domain, it was apparent that the C-terminal ER transactivation
      domain could substitute for that of c-Myb in inhibition of differentiation.
      Activation of Myb/ER in F-MEL cells had no effect upon the early and transient
      inhibition of entry into S phase associated with dimethyl sulfoxide (DMSO)
      induction. Further analyses of alpha-globin and PU.1 gene transcription suggested
      that c-Myb is unable to influence gene expression immediately following DMSO
      induction and that inhibition of F-MEL cell differentiation must therefore result
      from the function of c-Myb in the post-commitment period. Nonetheless, c-Myb had
      effects on the erythroid differentiation programme that were clearly dissociated
      from its role in cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589902
TI  - Parallel patterns of cell-specific gene expression during enterocyte
      differentiation and maturation in the small intestine of the rabbit.
AB  - Enterocytes are the major epithelial cell type of the small intestine. Their
      capacity to secret, absorb and digest specific ions and nutrients is dependent on
      their position along the length of the small intestine as well as their stage of
      development as they migrate and differentiate along the crypt-villus axis. In
      order to further understand the molecular processes that regulate enterocyte
      differentiation and function, this study has compared the levels of six mRNA
      species produced by genes expressed in rabbit enterocytes; specifically, the
      multidrug resistance (MDR1) gene encoding the 170-kDa P-glycoprotein, CaBP 9k,
      which encodes a putative intracellular calcium buffer, calbindin, LPH, APN, and
      AP which encode the brush-border hydrolases lactase-phlorizin hydrolase,
      aminopeptidase N and alkaline phosphatase, respectively, and SGLT1, encoding the
      brush border Na(+)-glucose cotransporter. The level of each mRNA species has been
      mapped along the small intestine using quantitative in situ hybridisation. This
      has revealed characteristic regional variations in the abundance of each of the
      mRNAs, supporting the opinion that there is a strong genetic component to the
      maintenance of gradients in epithelial function along the length of the small
      intestine. Analysis of the cellular accumulation of mRNA during enterocyte
      migration along the crypt-villus axis, over gut-associated lymphoid tissue, and
      at epithelial boundaries, has, by contrast, established a clear correlation in
      the expression of these genes. These data illustrate the dynamics of enterocyte
      gene expression, thereby providing an insight into the molecular mechanisms which
      co-ordinate the events of cell transformation that underlie functional
      differences between the epithelial populations of the small intestine.

PMID- 7589903
TI  - Fibroblast growth factor-mediated stimulation of differentiating teratocarcinoma
      cells: evidence for paracrine growth regulation.
AB  - Tera 2 human embryonal carcinoma cells proliferate rapidly in culture but are
      capable of differentiating into quiescent cells with neuronal features. We have
      characterized the effects of exogenous and endogenous fibroblast growth factors
      on the proliferation of differentiating Tera 2 cells. Exogenous basic fibroblast
      growth factor (bFGF) stimulated DNA synthesis and induced the proliferation
      associated antigen Ki 67 in differentiated Tera 2 cells. Heparin-binding growth
      factors isolated from the undifferentiated cells excerted a similar stimulatory
      effect on their differentiated derivatives. The functional potential of these
      endogenous growth factors was further demonstrated by their ability to stimulate
      plasminogen activator production by capillary endothelial cells. A major part of
      the growth promoting activity was removed by absorption with immobilized bFGF
      antibodies. bFGF was also detected in Tera 2 cells by immunoblotting. The
      production of heparin-binding growth-promoting activity decreased during
      differentiation. The results demonstrate a potential role for heparin-binding
      growth factors in the autocrine or paracrine growth regulation of teratocarcinoma
      cells.

PMID- 7589904
TI  - The use of toxicological research information: how and by whom.

PMID- 7589906
TI  - The evaluation of the developmental toxicity of hydrochlorothiazide in mice and
      rats.
AB  - Timed-pregnant CD-1 outbred albino Swiss mice and CD Sprague-Dawley rats were
      administered hydrochlorothiazide (HCTZ, USP) in corn oil by gavage during major
      organogenesis, Gestational Days (GD) 6 through 15. The doses administered were 0,
      300, 1000, or 3000 mg/kg/day for mice and 0, 100, 300, or 1,000 mg/kg/day for
      rats. Maternal clinical status was monitored daily during treatment. At
      termination (GD 17, mice; GD 20, rats), confirmed pregnant females (20-27 per
      group, mice; 36-39 per group, rats) were evaluated for clinical status and
      gestational outcome; each live fetus was examined for external, visceral, and
      skeletal malformations. In mice, no maternal mortality was observed. However,
      clinical signs including dehydration, piloerection, lethargy, and single-day
      weight loss appeared to be dose-related. HCTZ had no effect on maternal weight
      gain or water consumption, gravid uterine weight, relative maternal liver weight,
      or relative maternal kidney weight. There was no definitive evidence of
      embryotoxicity or fetal toxicity for mice on GD 17. Thus, the no observed adverse
      effect level (NOAEL) for both maternal and developmental toxicity was 3000
      mg/kg/day. In rats, HCTZ had no effect on maternal survival, clinical signs, or
      water consumption. Clinical signs were not dose-related. Maternal weight gain
      during treatment was depressed at 1000 mg/kg/day. Gravid uterine weight and
      relative maternal liver weight were unaffected. Relative maternal kidney weight
      was slightly (7-8%) increased at all dose levels, but there was no evidence of a
      dose response. Thus, the maternal NOAEL for rats was 300 mg/kg/day, based on
      decreased maternal weight gain during treatment at 1000 mg/kg/day.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589907
TI  - Developmental toxicity of dinitroaniline herbicides in rats and rabbits. I.
      Trifluralin.
AB  - The potential developmental toxicity of trifluralin was evaluated in rats and
      rabbits. Pregnant rats and rabbits were dosed once daily by gavage on Gestation
      Days 6-15 and 6-18, respectively. Doses for rats were 0, 100, 225, 475, or 1000
      mg/kg; doses for rabbits were 0, 100, 225, or 500 mg/kg. Cesarean sections were
      performed on rats and rabbits on Gestation Days 20 and 28, respectively. In rats,
      maternal toxicity was indicated in the 475 and 1000 mg/kg treatment groups by
      depression of body weights and food consumption. Fetal viability and morphology
      were not adversely affected at any dose level. Developmental toxicity was
      indicated at the 1000-mg/kg dose level by depression of fetal weight. The NOAEL
      for maternal toxicity in the rat was 225 mg/kg; the NOAEL for developmental
      toxicity in the rat was 475 mg/kg. In rabbits, maternal toxicity was indicated at
      the 225 and 500 mg/kg dose levels by abortions and/or deaths in conjunction with
      anorexia and cachexia. Developmental toxicity was indicated at the 500 mg/kg dose
      level by depressed fetal viability and weight. Fetal morphology was not adversely
      affected at any dose level. The NOAELs for maternal and developmental toxicity in
      the rabbit were 100 and 225 mg/kg, respectively. Based on these data, trifluralin
      did not exhibit selective toxicity toward the developing conceptus.

PMID- 7589908
TI  - Mechanism for species-specific induction of Leydig cell tumors in rats by
      lansoprazole.
AB  - Lansoprazole is a substituted benzimidazole which inhibits gastric acid secretion
      by inhibiting the hydrogen-potassium ATPase (proton pump) in the parietal cell.
      The finding of Leydig cell hyperplasia and Leydig cell tumors in 2-year oral
      studies in Sprague-Dawley rats but not in CD-1 mice prompted investigative
      studies to determine the mechanism for the Leydig cell changes. hCG challenge
      studies in Sprague-Dawley rats revealed decreased testosterone responsiveness in
      rats treated orally for 1 or 2 weeks with lansoprazole. After 4 weeks of daily
      oral treatment increases in serum LH and decreases in serum testosterone were
      detected within a few hours after dosing. In a study where 9-month-old male F344
      rats were given testosterone supplementation via Silastic implants and then
      treated with lansoprazole for 6 months, a high incidence of Leydig cell tumors
      was seen in lansoprazole-treated, unsupplemented rats, whereas no Leydig cell
      tumors were seen in testosterone supplemented rats. This implied that reduction
      of the normal feedback inhibition at the level of the hypothalamus and/or
      pituitary due to reduced testosterone levels, thus giving rise to elevated levels
      of LH, was involved in the induction of Leydig cell tumors by lansoprazole. In
      vitro studies with Leydig cells from rats using various stimulators and
      precursors of testosterone biosynthesis demonstrated that the most sensitive site
      for inhibition of testosterone synthesis by lansoprazole is the transport of
      cholesterol to the cholesterol side chain cleavage enzyme. The IC50s for
      inhibition of LH or hCG-stimulated testosterone synthesis in Leydig cells from
      rats, mice, and monkeys were 11-12, 8, and 24.7 micrograms/ml, respectively. In
      vitro studies with metabolites of lansoprazole revealed that three metabolites
      were more potent inhibitors of testosterone synthesis than the parent drug, two
      of them being at least 10 times more potent. These metabolites are present in
      rats at substantial levels but are undetectable in humans. The lack of induction
      of Leydig cell tumors in mice, lower sensitivity of primate Leydig cells, and the
      absence of testosterone synthesis-inhibiting metabolites in man suggest that
      Leydig cell tumors found in rats represent a species-specific sensitivity and
      does not imply a risk for clinical use in man.

PMID- 7589909
TI  - Evaluation of chick embryo neural retinal cell culture as a screen for
      developmental toxicants.
AB  - This paper describes a study to evaluate the concordance with in vivo results of
      an in vitro screen for developmental toxicants. The screen is a primary culture
      of chick embryo neural retina cells (CERC) which undergo processes of cell-cell
      recognition and interaction, growth, and differentiation over a 7-day culture
      period. Each of these developmentally significant events is measured separately
      as formation of multicellular aggregates, protein content, and glutamine
      synthetase activity, respectively. A total of 45 chemicals, 24 of which have been
      shown to be teratogenic at some dosage to mammalian embryos in utero, 7 of which
      are embryotoxic (but not teratogenic) in utero at high dosage, and 14 of which
      have not produced developmental toxicity in vivo, were evaluated in this assay by
      investigators who were blinded to the identity of the chemicals. Chemicals were
      tested up to concentrations that were frankly cytolethal, or up to a maximum of 5
      mg/ml. Chemicals were present only during the first 24 hr of culture. The
      chemicals were selected to be representative of a variety of chemical classes
      (e.g., solvents, metals, food additives, anticonvulsants, antineoplastics). In
      several cases, pairs of structurally similar compounds with different
      developmental toxic potencies (e.g., valproate and 2-en-valproate, formamide, and
      N,N-dimethylformamide) were tested. Of the 31 developmental toxicants, 25
      affected at least one endpoint in the assay at concentrations which are
      achievable in vivo (i.e., below the systemic concentration at a lethal dose),
      yielding a false-negative rate of 19%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589905
TI  - New molecular endpoints and methods for routine toxicity testing.
AB  - New molecular and instrumental techniques have made available many markers of
      cellular damage that can be evaluated in multiple tissues in vivo at low cost
      without compromising the normal conduct of in vivo toxicity evaluations, and
      without the need for substitution of new species or strains of animals. These
      techniques include (1) the activation of stress genes that respond to general
      classes of toxic agents and cellular damage at doses below those that cause frank
      toxicity; (2) electrophoretic methods for the detection of DNA strand breakage
      due to DNA degradation resulting from cell death or genotoxic damage; (3) the use
      of fluorescent chromosome-specific DNA probes that allow evaluation of stable
      chromosomal rearrangements, chromosomal breaks, and aneuploidy in laboratory
      animals; and (4) endogenous and exogenous (transgenic) reporter genes for the
      evaluation of in vivo gene mutation. Additionally, powerful new analytical
      techniques such as accelerator mass spectrometry make possible ultrasensitive
      measurements of metabolite binding to specific macromolecular targets and permit
      pharmacokinetics studies at very low doses. Often, identical or analogous
      endpoints can be measured in cellular models, in laboratory animals, and in
      humans, an approach that allows in vitro screening for product development, in
      vivo hazard identification, and early risk assessments in animal models and
      direct risk assessment in humans. These new in vivo techniques will greatly
      enhance our ability to extrapolate laboratory data to human health risk.

PMID- 7589910
TI  - Dose-response assessments for developmental toxicity. IV. Benchmark doses for
      fetal weight changes.
AB  - Recently, most attention on the application of benchmark dose (BMD) techniques to
      toxicology data has focused on quantal measures of response. Before the
      advantages of the BMD approach can be exploited in the risk assessment process,
      it is important that continuous measures of response also be modeled
      appropriately. In this study, we examined a variety of approaches to estimating
      BMDs for a change in fetal weight following chemical exposure from a total of 85
      developmental toxicity experiments. We modeled the change in the mean fetal
      weight of a litter in response to treatment using a continuous power model, as
      well as reductions in the weight of individual fetuses within litters (defined as
      falling below a preset level) using a log-logistic model which incorporates
      litter size as a covariable and considers intralitter correlations. For the
      litter-based approach, several methods of defining a benchmark effect (BME) were
      considered, including a percentage change in mean litter weight, a change in mean
      litter weight relative to variability in the control group, and a reduction in
      the mean litter weight to some point on the control group distribution curve. For
      the fetus-based approach, we examined several BME options on the cumulative
      frequency distribution of the control fetuses for defining a low weight fetus and
      calculated several levels of additional risk. BMDs for four litter-based BMEs (a
      difference of 5% in mean fetal weight, a decrease to the 25th percentile mean
      weight of control litters, a decrease in the mean weight by 2 standard errors,
      and a decrease of 0.5 standard deviation units) and two fetus-based BMEs (a 5%
      added risk of weighing less than the 5th percentile of control weights and a 10%
      added risk of weighing less than the 10th percentile) showed strong similarities
      to each other and to statistically derived NOAELs. In addition to providing
      comparison with the NOAEL as a reference value, these analyses provided
      confirmation of the advantages of the BMD approach over the NOAEL in terms of the
      influence of dose spacing and dose selection. Combined with our previous analyses
      of quantal endpoints of fetal effects, this information provides a firm basis
      upon which to implement the benchmark dose concept in developmental toxicity risk
      assessments.

PMID- 7589911
TI  - Inhalation oncogenicity bioassay in rats and mice with vinyl fluoride.
AB  - The purpose of this study was to assess the oncogenic potential of vinyl fluoride
      in rats and mice when administered by inhalation. Male and female rats and mice
      were exposed to 0, 25, 250, or 2500 ppm vinyl fluoride 6 hr per day, 5 days per
      week, for 2 years (rats) or 18 months (mice). Slight body weight gain decrements
      were noted in groups of vinyl fluoride-exposed rats and mice. No significant
      clinical signs of toxicity were noted other than an increase in the incidence of
      palpable masses in the region of the mammary gland in female mice exposed to
      vinyl fluoride. Survival was decreased in male rats and mice of the 250 and 2500
      ppm groups and female rats and mice of all vinyl fluoride-exposed groups compared
      to controls. Urinary fluoride excretion, an indicator of vinyl fluoride
      metabolism, increased with concentration and time although the dose relationship
      appeared to plateau at concentrations > or = 250 ppm. Gross observations made at
      necropsy of rats supported histological observations of hepatic hemangiosarcoma,
      hepatocellular adenoma and carcinoma, hepatic foci of clear cell and basophilic
      alteration, hepatic sinusoidal dilatation, metastatic lung tumors, and Zymbal's
      gland tumors. Hepatic hemangiosarcoma was the sentinel lesion in rats. Gross
      observations made at necropsy of mice supported histological observations of
      bronchioloalveolar adenoma and hyperplasia, hepatic hemangiosarcoma and
      hepatocellular hyperplasia with angiectasis and peliosis, and mammary gland
      adenocarcinoma and hyperplasia. Bronchioloalveolar adenoma appeared to be the
      sentinel lesion in mice. The spectrum of vinyl fluoride-induced tumors is similar
      to that induced by other monohaloethylenes in rats and mice. Under the conditions
      of this study, vinyl fluoride was carcinogenic in male and female rats and mice
      at concentrations greater than or equal to 25 ppm.

PMID- 7589912
TI  - Antidotal efficacy of newly synthesized dimercaptosuccinic acid (DMSA) monoesters
      in experimental arsenic poisoning in mice.
AB  - The efficacy of four newly synthesized monoesters of meso-2,3-dimercaptosuccinic
      acid (DMSA), mono-i-amyl- (Mi-ADMS), mono-n-amyl- (Mn-ADMS), mono-i-butyl- (Mi
      BDMS), and mono-n-butyl-meso-2,3-dimercaptosuccinate (Mn-BDMS) in increasing
      survival and arsenic elimination in experimental arsenic poisoning was
      investigated. Male mice (strain NMRI) received arsenite sc (survival study: 130
      mumol/kg, 7 mice/group; elimination study: 85 mumol/kg (LD5) together with a
      tracer dose of 73As(III), 6 mice/group). After 30 min mice were treated with 0.7
      mmol/kg of DMSA or a monoester ip or via gastric tube (ig). Control animals
      received saline ip. In the survival study mice were observed for 30 days. In the
      elimination study, the 73-arsenic content of several organs (blood, liver, heart,
      lung, kidneys, spleen, testes, brain, small intestine, large intestine, muscle,
      and skin) was measured 0.5, 2, 4, 6, and 8 hr after the arsenic injection using a
      gamma counter. Survival increased correspondingly well with the increase of
      arsenic elimination. DMSA, Mi-ADMS, Mn-ADMS, Mi-BDMS, and Mn-BDMS markedly
      decreased arsenic content in most organs as soon as 1.5 hr after treatment. Only
      in small and large intestine were higher arsenic amounts found, indicating a
      shift in arsenic elimination from the renal to the fecal route, and thereby
      suggesting a protective effect for the kidneys. Given ip, the monoesters turned
      out to be similarly as effective as the parent drug DMSA. Following ig treatment,
      the DMSA monoesters Mi-ADMS and Mn-ADMS seemed to be superior to DMSA with regard
      to survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589913
TI  - Tirilazad mesylate--effects of the 21-aminosteroid on the lymphoid system of
      laboratory animals: a comparison with the glucocorticoid methylprednisolone.
AB  - Four-week toxicity studies with the 21-aminosteroid tirilazad mesylate were
      conducted in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys to support
      development of the drug for use in various clinical syndromes of injury to the
      central nervous system of humans. As the immune system is involved in many of the
      obvious side effects of glucocorticoids used currently for this indication,
      particular attention was directed to the lymphoid system; results were contrasted
      with similar data from studies with methylprednisolone, a classical
      glucocorticoid. Administration of tirilazad mesylate to rats, dogs and monkeys
      for 4 weeks had no effects at the highest doses tested on parameters assessed,
      including absolute peripheral blood lymphocyte counts, thymus or adrenal weights,
      circulating levels of cortisol, or lymphocyte proliferation response to
      phytohemagglutinin-P. Germinal centers in lymphoid tissues from dogs given high
      doses of tirilazad contained small numbers of macrophages with vacuolated
      cytoplasm but no other changes; lymphoid tissues in rats and monkeys given
      tirilazad were morphologically normal. Administration of methylprednisolone for a
      similar duration in rats and dogs at high dose levels was associated with
      increased death rates due to bacterial infections, markedly decreased peripheral
      blood lymphocyte counts and weights of thymus and adrenal glands, and prominent
      lymphoid atrophy as well as decreased circulating levels of cortisol. Female dogs
      infused for 10 days with a high dose of methylprednisolone had depression of the
      in vitro proliferation response of peripheral blood lymphocytes to
      phytohemagglutinin-P.

PMID- 7589914
TI  - Comparative toxicokinetics of methanol in the female mouse and rat.
AB  - The toxicokinetics of methanol in female CD-1 mice and Sprague-Dawley rats were
      examined to explore the possibility of species differences in the disposition of
      the compound. Mice received a single dose of 2.5 g/kg methanol either po (by
      gavage) or i.v. (as a 1-min infusion). Rats received a single oral dose of 2.5
      g/kg methanol. As expected, the disposition of methanol was nonlinear in both
      species. Data obtained after i.v. administration of methanol to mice were well
      described by a one-compartment model with Michaelis-Menten elimination. Blood
      methanol concentration--time data after oral administration could be described by
      a one-compartment (mice) or two-compartment (rats) model with Michaelis-Menten
      elimination from the central compartment and biphasic absorption from the
      gastrointestinal tract. Kinetic parameters (Vmax for elimination, apparent volume
      of the central compartment [Vc], first-order rate constants for
      intercompartmental transfer [k12 and k21], and first-order absorption rate
      constants for fast [kAF] and slow [kAS] absorption processes) were compared
      between species. When normalized for body weight, mice evidenced a higher maximal
      elimination rate than rats (Vmax = 117 +/- 3 mg/hr/kg vs 60.7 +/- 1.4 mg/hr/kg
      for rats). The contribution of the fast absorption process to overall methanol
      absorption also was larger in the mouse than in the rat.

PMID- 7589915
TI  - Influence of lead on mineralization during bone growth.
AB  - Lead will inhibit skeletal development and localize in areas of bone formation
      and resorption, but the mechanisms of lead toxicity in bone are largely unknown.
      This study used an ectopic bone (plaque) induction method to investigate the
      effect of lead on mineralization of cartilage in growing bone. Demineralized bone
      matrix was subcutaneously implanted in male Long-Evans rats to induce plaque
      formation. Of 64 rats which were provided deionized water, 32 were implanted with
      control matrix (control group). The remaining 32 rats were implanted with matrix
      containing a target concentration of 200 micrograms lead/g of plaque tissue as
      ectopic bone (lead-added group). Another group of 32 rats was continuously
      exposed to 1000 ppm lead in drinking water and subcutaneously implanted with
      control matrix (drinking water-lead group). Plaques were taken for analysis on
      Days 8 and 12 postimplantation. Alkaline phosphatase activity and cartilage
      mineralization were obliterated in lead-added plaques. However, calcium
      deposition was markedly enhanced in the lead-added plaques. Decreased alkaline
      phosphatase in Day 8 drinking water-lead plaques followed increased Day 12
      drinking water lead plaque calcification. Enhanced cartilage calcification and
      reduced alkaline phosphatase activity in the drinking water-lead plaques was
      consistent with effects observed in the metaphyseal regions of bone in lead
      exposed rats and pigs. The results of this study suggest that lead adversely
      influences bone development through disruption of mineralization during growth.

PMID- 7589918
TI  - Mechanism of protection by diethyldithiocarbamate against cisplatin ototoxicity:
      antioxidant system.
AB  - This investigation was undertaken to explain the possible, mechanism(s) of
      protection by diethyldithiocarbamate (DDTC) against cisplatin ototoxicity. Male
      Wistar rats (250-275 g) underwent pretreatment auditory brain stem-evoked
      responses (ABRs). The different groups of rats were injected as follows: (1)
      cisplatin (16 mg/kg i.p.), (2) cisplatin plus DDTC (16 mg/kg i.p. + 600 mg/kg,
      s.c.), and (3) control rats. Post-treatment ABRs were performed after 3 days and
      the rats were euthanized and cochleae were harvested. The cochleae were analyzed
      for glutathione (GSH) and oxidized glutathione, by HPLC, and for the activities
      of the antioxidant enzymes, and malondialdehyde levels, by spectrophotometry. The
      cisplatin-injected rats showed a threshold elevation of 36 +/- 3.05 dB above the
      pretreatment thresholds using click stimulus. Rats treated with cisplatin and
      then DDTC did not show a significant elevation of hearing threshold. DDTC
      mediated protection was associated with higher levels of GSH (0.81 +/- 0.11
      nmol/mg tissue), compared to 0.45 +/- 0.02 nmol/mg tissue following
      administration of cisplatin alone. Administration of cisplatin + DDTC restored
      the cochlear GSH-Px activity to control level. Cisplatin-treated rats were found
      to have decreased GSH-Px activity (75% of control). Cochlear SOD and CAT
      activities and MDA levels showed a decreasing trend in the animals injected with
      cisplatin + DDTC, compared to cisplatin-alone-treated rats. These data suggest
      that the protection conferred by DDTC against cisplatin ototoxicity is associated
      with sparing of the cochlear GSH/GSH-Px.

PMID- 7589917
TI  - Toxicity of PCB 77 (3,3',4,4'-tetrachlorobiphenyl) and PCB 118 (2,3',4,4'5
      pentachlorobiphenyl) in the rat following subchronic dietary exposure.
AB  - The toxicity of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and 2,3',4,4',5
      pentachlorobiphenyl (PCB 118) was investigated in rats following subchronic
      dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats
      were administered PCB 77 in the diet at 0, 10, 100, 1000, or 10,000 ppb for 13
      weeks. PCB 118 was administered to males in the diet at 0, 10, 100, 1000, and
      10,000 ppb, while the female groups received 0, 2, 20, 200, or 2000 ppb of the
      congener for 13 weeks. Growth rate and food consumption were not affected by
      treatment. No clinical signs of toxicity were observed. Increased spleen weight
      occurred in male rats fed 1000 or 10,000 ppb PCB 77. Male rats receiving 10,000
      ppb PCB 118 had increased liver weight and hepatic ethoxyresorufin O-deethylase
      (EROD) activity. Increased hepatic EROD activity but not liver weight was
      observed in female rats given the 2000-ppb PCB 118 diet. Increased EROD activity
      was also noted in male rats given 10,000 ppb and in female groups receiving 1000
      or 10,000 ppb PCB 77. Male rats exposed to 10,000 ppb PCB 77 had decreased
      vitamin A in the liver and lung and elevated levels in the kidney. Liver vitamin
      A of both 1000- and 10,000-ppb PCB 77 female groups was decreased. PCB 118 had no
      effects on tissue vitamin A at the levels studied. No hematological changes or
      serum biochemical changes were seen in any of PCB 118- and PCB 77-treated groups,
      nor were liver uroporphyrin levels altered. A reduction in dopamine and
      homovanillinic acid in substantia nigra region of the brain was observed in
      female rats fed 2000 ppb PCB 118, while 10,000 ppb PCB 77 was associated with an
      elevation in 3,4-dihydroxyphenylacetic acid in the nucleus accumbens region of
      male rat brains. Mild to moderate changes were observed in the liver and thyroid
      of rats given PCB 77 or PCB 118. PCB 118 accumulated in a dose-dependent manner
      in fat and to a much lesser extent in liver. In contrast, very low levels of PCB
      77 residue were found in the tissues examined. Based on the above data it was
      concluded that NOAEL of PCB 77 is 100 ppb in diet or 8.7 micrograms/kg and that
      of PCB 118 is 200 ppb in diet or 17 micrograms/kg body wt/day.

PMID- 7589919
TI  - Reversal of oxophenylarsine-induced inhibition of glucose uptake in MDCK cells.
AB  - It has been shown that oxophenylarsine (PhAsO) inhibits glucose uptake in MDCK
      cells. In addition to the known impairment of cellular energy metabolism, this
      inhibition may contribute to the acute toxicity of trivalent organic arsenicals.
      We have investigated the effect of BAL, DMPS, DMSA, and other sulfur compounds on
      cellular incorporation of [U-14C]PhAsO and their efficacy to revert PhAsO-induced
      inhibition of glucose uptake. In the presence of [U-14C]PhAsO (2 microM), the
      radiolabel was steadily accumulated by the cells over 150 min without any signs
      of severe cell damage (e.g., altered morphology, increased LDH release). A
      notable decrease of cellular ATP was only observed at 150 min, whereas within 30
      min uptake of D-[6-(14)C]glucose was reduced to 40% of controls. When BAL, DMPS,
      or DMSA was added after 30 min, the inhibition of glucose uptake was reversed,
      accompanied by a decrease in cell-associated radiolabel from [U-14C]-PhAsO. Water
      soluble DMPS and DMSA required longer times than BAL for comparable effects. 2,3
      Bis(acetylthio)propanesulfonamide, a thioester derivative, and dithiothreitol, a
      1,4-dithiol, were effective only with the highest concentration tested (200
      microM). 2-Mercaptoethanol neither reversed inhibition of glucose uptake nor
      influenced [U-14C]PhAsO incorporation. Our results show that inhibition of
      glucose uptake is a very early event in PhAsO cytotoxicity which occurs before
      any decrease of cellular energy metabolism and/or full cellular loading with
      arsenic comes into effect. The more rapid onset of action of lipophilic BAL
      compared to PhAsO action.

PMID- 7589916
TI  - Hepatic and adrenal toxicity of a novel lipid regulator in beagle dogs.
AB  - PD 138142-15 is a substituted urea hypolipidemic and potential anti
      atherosclerotic agent. To determine the toxicity of PD 138142-15, beagle dogs
      were given oral doses of 1, 10, 30, and 100 mg/kg daily for 13 weeks. Two animals
      at 100 mg/kg were euthanized during Week 5 due to poor condition. Clinical
      findings included decreased serum albumin at > or = 30 mg/kg, and increased ALP
      (up to 30-fold) and 5'-nucleotidase activities (up to 9-fold) at doses > or = 10
      mg/kg. ALT and AST activities were elevated only at 100 mg/kg. There was a two-
      to threefold increase in cytochrome P450 content of hepatic microsomes from all
      treated animals and increases in liver weights at 10 mg/kg and above. Hepatic
      changes included hepatocellular hypertrophy and increased cytoplasmic
      eosinophilia at > or = 10 mg/kg; single cell necrosis of hepatocytes was noted in
      moribund animals. ACTH-stimulated cortisol levels were decreased at 30 and 100
      mg/kg. Adrenal cholesterol esters were decreased at 10 mg/kg and above, while
      total adrenal cholesterol was decreased at > or = 30 mg/kg. These changes
      correlated with adrenal cortical zonal atrophy, principally of the zona
      fasciculata and zona reticularis, present at 30 and 100 mg/kg. Plasma
      concentrations of PD 131842-15 increased with increasing dose; plasma levels were
      significantly lower during Week 12 than those on Day 1, possibly due to
      autoinduction. Overt hepatotoxicity occurred at 100 mg/kg, whereas hepatic
      changes at 10 and 30 mg/kg were consistent with cytochrome P450 induction. The
      hepatic lesions were reversible within 4 weeks, while adrenal lesions were still
      evident after 4 weeks without treatment.

PMID- 7589921
TI  - Studies on the tumor initiation/promotion potential of six middle distillates
      (MDs) in mouse skin.
AB  - Six middle distillates (MDs) were tested for tumor initiating/promoting activity
      after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the
      control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed
      by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the
      tumor-initiating activity, 50 microliters of neat MDs was administered for 5 days
      with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation
      50 microliters of the neat MDs was administered twice weekly until Week 28. For
      the examination of complete carcinogenic activity, one MD was given without DMBA
      initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring
      during the initiation with the MDs, were completely reversible during the 2-week
      treatment-free period after initiation. Similar skin findings were observed
      during promotion with the MDs. Regarding the number of affected animals and the
      severity of the response, TPA was more irritating than the MDs. The initiation
      study revealed skin tumors for the DMBA/TPA control (30/30), MD 57,389 (14/30),
      MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study
      revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and
      57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without
      DMBA initiation thus indicating that it also is a complete carcinogen. MD 57,399
      caused neither initiating nor promoting effects. The tumors observed were
      diagnosed histopathologically predominantly as squamous cell papillomas.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7589920
TI  - Central nervous system toxicity of manganese. I. Inhibition of spontaneous motor
      activity in rats after intrathecal administration of manganese chloride.
AB  - The intrathecal administration of MnCl2 to young male rats caused dopamine
      depletion in the caudate-putamen and a decrease in spontaneous motor activity.
      Our experiments demonstrate that in the young rat: (a) the lateral choroid plexus
      protects the cerebrospinal fluid (CSF) from high concentrations of Mn in the
      blood by sequestering and thus preventing large amounts of this metal ion from
      entering the CSF. As blood Mn levels rise, the lateral choroid plexus may become
      overwhelmed and leak an increasing amount of Mn into the CSF. (b) The lateral
      choroid plexus does not remove Mn2+ from the CSF. (c) The injection of MnCl2 into
      the CSF of rats caused a rapid decrease in spontaneous motor activity which is
      dose-dependent and reversible under the present experimental conditions.
      Intrathecal Mn results in a substantial decrease in striatal dopamine but not
      homovanillic acid or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations and is
      associated with an increase in the Mn concentration of the substantia nigra and
      caudate-putamen.

PMID- 7589922
TI  - Determination of a no-observed-effect level for developmental toxicity of
      ethylene glycol administered by gavage to CD rats and CD-1 mice.
AB  - Previous studies have indicated that ethylene glycol (EG) is a developmental
      toxicant in rats and mice primarily when ingested. This study was designed to
      establish no-observed-effect levels (NOELs) for developmental toxicity of EG
      administered by gavage in both rodent species. Dams were administered EG on
      Gestation Days 6-15; rats were given 0, 150, 500, 1000, or 2500 mg EG/kg/day;
      mice were dosed with 0, 50, 150, 500, or 1500 mg EG/kg/day. In rat dams given
      2500 mg EG/kg/day, water consumption was increased during treatment and body
      weights were reduced throughout gestation; liver and kidney weights were
      increased at euthanization (Gestation Day 21). Relative liver weights were also
      increased at 1000 mg/kg/day. Effects observed in rat fetuses at 2500 mg/kg/day
      included the following: hydrocephaly; gastroschisis; umbilical hernia; fused,
      duplicated, or missing arches, centra, and ribs; poor ossification in thoracic
      and lumbar regions; and reduced body weights. Reduced body weights, duplicated or
      missing ribs, centra, and arches, and poor ossification were also observed in rat
      fetuses at 1000 mg/kg/day. In mice, there was no apparent treatment-related
      maternal toxicity. In mouse fetuses (Gestation Day 18), effects were observed at
      1500 mg/kg/day and included reduced body weights, fused ribs and arches, poor
      ossification in thoracic and lumbar centra, and increased occurrence of an extra
      14th rib. At 500 mg/kg/day, slight reductions in fetal body weight and increased
      incidences of extra ribs were observed. Under conditions of these studies, NOELs
      for developmental toxicity were 500 mg/kg/day for rats and 150 mg/kg/day for
      mice, indicating that mice were more susceptible than rats to the teratogenic
      effects of EG.

PMID- 7589923
TI  - Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners:
      nonadditive (antagonistic) interactions.
AB  - The dose-response inhibition of the splenic plaque-forming cell (PFC) response
      and serum IgM units to the antigen, trinitrophenyl-lipopolysaccharide, was
      determined for several polychlorinated biphenyl (PCB) mixtures and congeners in
      female B3C3F1 mice. The ED50 values for Aroclor 1260-, 1254-, 1248-, and 1242
      induced immunotoxicity varied by less than twofold from 355 to 699 mg/kg. The
      range of ED50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'
      tetrachlorobiphenyl, 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, 2,3,3',4,4'
      pentaCB, 2,3',4,4',5-pentaCB, 2,3,3',4,4',5-hexaCB, 2,3,3',4,4',5,5'-heptaCB,
      2,2',3,3',4,4',5-heptaCB, and 2,2',3,4,4',5,5'-heptaCB were 4.6 to 4.9, 134 to
      245, 4.7 to 7.0, 6.9 to 11.1, 88,000 to 121,000, 122,000 to 132,000, 99,000 to
      157,000, 89,000 to 129,000, 117,000 to 240,000, and 132,000 to 238,000
      micrograms/kg, respectively. The immunotoxicity-derived toxic equivalency factors
      (TEFs) for these congeners could be calculated from the ED50 (TCDD)/ED50
      (congener) ratios and the TEF values were within the range of those previously
      determined for other aryl hydrocarbon receptor-mediated responses. Based on the
      known concentrations of these congeners in the PCB mixtures, TCDD or toxic
      equivalents (TEQs) in the mixture were calculated [i.e., TEQ = sigma (PCBcongener
      x TEF)] using the immunotoxicity-derived TEFs (plaque-forming cells/10(6) viable
      cells). TEQ values for Aroclors 1260, 1254, 1248, and 1242 were 16.0, 54.4,
      260.4, and 197 ppm, respectively. Based on the ED50 value for the
      immunosuppressive activity of TCDD (4.8 micrograms/kg), the calculated ED50
      values for immune suppression by Aroclors 1260, 1254, 1248, and 1242 were 300,
      88, 18, and 24 mg/kg, respectively. The ED50 (observed)/ED50 (calculated) ratios
      were 1.2, 5.9, 21, and 22.0 for Aroclors 1260, 1254, 1248 and 1242,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589925
TI  - Toxicokinetics of a single 50 mg/kg oral dose of [2,3-14C]acrylamide in White
      Leghorn hens.
AB  - A single oral dose of [2,3-14C]acrylamide (50 mg/kg) was administered in water to
      adult white leghorn hens. Seven groups of three hens were euthanized between 2
      and 120 hr after administration. Within 12 hr, the hens excreted 70% of the
      administered dose, and more than 99% within 48 hr. Blood, plasma, liver, and
      muscle contained the greatest percentage of administered dose at 4 hr after
      dosing. Less than 0.02% of the administered dose appeared in brain at any time.
      Radiolabel accumulated in the eggs, with 0.52% of the administered dose
      accumulated within 5 days. Binding of radiolabel to erythrocytes was minimal.
      Elimination of radiolabel from all tissues was biphasic. Terminal elimination
      half-lives for 14C were longer than 10 days, at which time less than 0.2% of the
      administered dose remains in the tissues. Distribution half-lives for 14C were
      longest for whole blood and shortest for kidney. Radioactivity in the blood and
      plasma reached a peak at between 4 and 12 hr. Most of this radioactivity was
      identified as acrylamide, which disappeared biexponentially with terminal
      elimination half-lives longer than 10 days. Distribution half-lives for
      acrylamide were longest in brain and shortest in whole blood. These results show
      that orally administered acrylamide is poorly absorbed and rapidly eliminated
      from hens and accumulates in their eggs in a nonextractable form.

PMID- 7589924
TI  - The reproductive and developmental toxicity of indium in the Swiss mouse.
AB  - Indium is increasingly used in a variety of industries, and while there are few
      studies of its developmental toxicity, ther are no reports of its potential
      reproductive toxicity. These studies were undertaken to investigate the possible
      reproductive toxicity of indium and to determine the relative vulnerability of
      males and females. We used, initially, a 21-day combined
      developmental/reproductive toxicity protocol. Oral exposures to InCl3 ( < or =
      250 mg/kg) were without effect on the male reproductive system or liver. A kidney
      effect was demonstrated in males by a decrease in urinary N-acetyl
      glucosaminidase. The ability of females to become pregnant was unaffected.
      However, fetal development was adversely affected, manifested as increased
      intrauterine deaths in the presence of reduced maternal weight gain. A
      developmental toxicity study identified no increase in fetal malformations, but
      verified the increased fetal deaths, in the absence of effects on adjusted
      maternal body weight. In vitro toxicity studies showed that the embryolethality
      was at least in part a result of direct toxicity to the conceptus, with effective
      doses in the low micromolar range. A limited disposition study showed that
      fetuses contained low micromolar concentrations of indium, more indium than
      maternal liver, and comparable to levels that were toxic in vitro. Although
      studies of greater exposure duration are required for risk assessment, these data
      indicate that fetal development is likely to be more affected by indium than
      female or male reproduction, with adverse effects occurring at low micromolar
      levels in vivo and at exposures that may or may not affect body weight.

PMID- 7589926
TI  - Effects of propylene oxide on nasal epithelial cell proliferation in F344 rats.
AB  - In chronic inhalation studies, propylene oxide (PO), widely used in the chemical
      and food industries, induced nasal tumors in F344 rats. Nonneoplastic findings of
      the chronic studies suggest a strong cytotoxic and proliferative component in the
      mechanism of PO carcinogenicity. A 4-week cell proliferation study was conducted
      to establish a no-observed-adverse-effect level (NOAEL) for nonneoplastic changes
      in the nasal epithelium of rats. Male F344 rats were exposed to 0, 10, 20, 50,
      150, or 525 ppm PO vapor for up to 4 weeks with up to 4 weeks of recovery.
      Histopathology showed that the incidence and severity of respiratory epithelial
      hyperplasia increased with exposure time and regressed after termination of
      exposure with complete recovery after 4 weeks. Similarly, cell proliferation, as
      determined by bromodeoxyuridine incorporation into replicating cells, was
      elevated following 1 and 4 weeks of exposure but decreased to control values
      after 1 week of recovery. Degeneration of the olfactory epithelium was found
      after 4 weeks of exposure with a decrease in incidence and severity after
      termination of exposure. Cell proliferation at this site was elevated during the
      4-week exposure period and 1 week postexposure with return to control values
      after 4 weeks of recovery. Based on the cytotoxic and proliferative findings, the
      NOAEL for PO in nasal epithelium is 50 ppm.

PMID- 7589927
TI  - Oncogenic potential of inhaled hydrazine in the nose of rats and hamsters after 1
      or 10 1-hr exposures.
AB  - Hydrazine (N2H4) is used as a fuel for missiles and standby power systems of
      operational military aircraft. Maintenance of missiles and aircraft may result in
      accidental human exposure to high concentrations for brief periods of time. The
      purposes of this study were to assess the oncogenic potential of N2H4 in rats and
      male hamsters exposed to a high concentration of N2H4 for repeated short
      exposures and to investigate the relationships of acute and subchronic effects of
      N2H4 to nasal tumorigenesis. In phase 1 (acute and subchronic) and Phase 2
      (lifetime experiments, groups of male and female Fischer 344 rats and male Syrian
      golden hamsters were exposed by inhalation to 0, 75 (Phase 2 only), or 750 ppm
      N2H4 for 1 (acute) or 10 (subchronic) 1-hr weekly exposures. Rodents were
      euthanized 24 hr after exposures 1 and 10 and 24 to 30 months poststudy
      initiation. Significant reductions in body weight were observed in N2H4-treated
      rodents compared to controls during the exposure interval. No hydrazine-induced
      mortality was detected. Histopathologic examination after the acute and
      subchronic exposures revealed degeneration and necrosis of transitional,
      respiratory, and olfactory epithelia in the anterior nose and, in rats exposed
      subchronically, squamous metaplasia of the transitional epithelium. Minimal to
      mild rhinitis resulted from N2H4 exposures. Apoptosis was observed in olfactory
      and squamous metaplastic transitional epithelium. Lesions occurred at sites
      reportedly having high air-flow and generally appeared to be more severe in the
      anterior portion of the nose. By 24 months, the squamous metaplastic transitional
      epithelium reverted back to normal-appearing transitional epithelium. By 24+
      months, low incidences (sexes combined) of hyperplasia (5/194, 2.6%) and
      neoplasia (11/194, 5.7%) were detected, principally in the transitional
      epithelium of the 750 ppm N2H4-treated rats. A similar incidence of hyperplasia
      (2/94, 2%) and neoplasia (5/94, 5.3%) was detected in the high-exposure group of
      hamsters. The location and type of N2H4-induced proliferative lesions were
      similar to those reported in a chronic N2H4-exposure study (5.0 ppm x 6 hr/day x
      5 days/week for 1 year) conducted in our laboratory, but the chronic study had
      much higher incidences (rats, sexes combined: hyperplasia 15.5% vs 2.6% and
      polypoid adenoma 44.6% vs 5.2%). The product (CD) of concentration + time was the
      same (750 ppm hours) for the high-dose groups for both studies, but the duration
      of exposure was 150 x longer and the concentration was 150 x lower in the chronic
      study.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7589928
TI  - Evaluation of the developmental toxicity of ethylene glycol aerosol in CD-1 mice
      by nose-only exposure.
AB  - Ethylene glycol (EG; CAS No. 107-21-1) is teratogenic to mice by whole-body (WB)
      exposure to aerosol (1000-2500 mg/m3). The WB results were confounded by possible
      exposure from ingestion after grooming and/or from percutaneous absorption.
      Therefore, CD-1 mice were exposed to EG aerosol (MMAD 2.6 +/- 1.7 microns) on
      Gestational Days (GD) 6 through 15, 6 hr/day, by nose-only (NO) (0, 500, 1000, or
      2500 mg/m3) or WB exposures (0 or 2100 mg/m3, as positive control), 30/group.
      Five additional "satellite" females each at 2500 mg/m3 NO and 2100 mg/m3 WB were
      exposed on GD 6 for measurement of EG on fur. Control environments were water
      aerosol (4200 mg/m3 for NO; 2700 mg/m3 for WB). Females were weighed and
      evaluated for clinical signs and water consumption throughout gestation. On GD
      18, maternal uterus, liver, and kidneys (2) were weighed, with kidneys examined
      microscopically. Corpora lutea and implantation sites were recorded. Live fetuses
      were weighed, sexed, and examined for structural alterations. For NO dams, kidney
      weights were increased at 1000 and 2500 mg/m3; no renal lesions and no other
      treatment-related maternal toxicity were observed. There were no effects on pre-
      or postimplantation loss; fetal body weights/litter were reduced at 2500 mg/m3.
      At 2500 mg/m3, incidences of fused ribs and skeletal variations were increased.
      The 2500 mg/m3 NO satellite animals had approximately 330 mg/kg extractable EG.
      The WB group exhibited maternal and developmental toxicity including increased
      fetal skeletal malformations and variations, confirming previous results, with
      1390 mg/kg extractable EG on fur. Therefore, exposure of CD-1 mice to a
      respirable EG aerosol during organogenesis by NO inhalation resulted in minimal
      maternal toxicity at 1000 and 2500 mg/m3 and developmental toxicity at 2500
      mg/m3. The NOAEL was 500 mg/m3 NO for maternal and 1000 mg/m3 NO for
      developmental toxicity. This study supports the interpretation of the initial EG
      WB results as due to systemic exposure from noninhalation routes since limiting
      noninhalation routes prevented almost all of the effects (including
      teratogenicity) observed in mice after WB exposure.

PMID- 7589930
TI  - Toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley
      rats including placental and lactational transfer to fetuses and neonates.
AB  - The toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in virgin female
      Sprague-Dawley (S-D) rats, the effects of pregnancy, parturition, and lactation
      on the distribution and/or redistribution of TCDD, and placental and lactational
      transfer to fetuses and neonates were investigated. Doses of 5.6 micrograms/kg of
      14C-labeled TCDD were given i.v. either to virgin rats or to pregnant rats on Day
      18 of gestation and 1 day postparturition, respectively. Virgin females were
      terminated on Day 1, 2, 4, 8, 16, or 32, pregnant rats on Day 1, 2, 4, or 8,
      after dosing to collect tissues. Two groups of neonates, which were born either
      to TCDD-treated or nontreated dams were cross-fostered beginning on the first day
      after birth to simulate exposure to TCDD either by lactational transfer only or
      by both placental and lactational transfer. Serum and 18 different tissues were
      collected from virgin rats to evaluate the kinetic profile of TCDD. Serum and
      tissue samples from liver, kidney, brown, and white adipose tissue were collected
      from pregnant and postparturition rats. Liver samples from fetuses and neonates
      were obtained on Gestational Days 19 and 20, or postnatally on Days 1 and 5. TCDD
      equivalents were calculated from measurement of radioactivity. The results show
      that the profile of TCDD distribution in virgin female rats was similar to that
      in male rats but that the concentration of TCDD in most tissues was higher in
      females than in males.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589929
TI  - Biochemical and biophysical characterization of pulmonary surfactant in rats
      exposed chronically to cigarette smoke.
AB  - The pulmonary surfactant plays an important role in the gas exchange functions of
      the lungs. Although previous studies suggest that cigarette smoking alters the
      pulmonary surfactant system in human smokers, the nature of such changes is
      poorly understood. The aim of the present study was to determine if biochemical
      and biophysical properties of pulmonary surfactant are affected in rats following
      chronic exposure to cigarette smoke. Female Sprague-Dawley rats were exposed
      daily to smoke from the University of Kentucky high tar/high nicotine reference
      cigarettes, twice a day, for 60 weeks in a nose-only exposure system. Blood
      carboxyhemoglobin, plasma cotinine, and pulmonary aryl hydrocarbon hydroxylase
      activity measurements showed that animals effectively inhaled smoke during
      exposures. At termination, the bronchoalveolar lavage fluids (BALF) and the lung
      tissues were collected for biochemical and biophysical analyses of surfactant.
      The total phospholipid content of the BALF and the lung tissues from room control
      (RC), sham-treated (SH), and smoke-exposed (SM) animals were the same among the
      different groups. However, disaturated phosphatidylcholine (DSPC) levels in the
      BALF were significantly decreased in SM rats compared to RC or SH groups. In
      contrast, the lung tissue DSPC content in SM rats was not significantly different
      from that of control groups. Phospholipid profile analysis of the BALF also did
      not reveal any significant differences among other major constituents of
      surfactant from control and SM animals. The organic extracts of BALF obtained
      from different animal groups were assessed for surface activity using a Wilhelmy
      balance. The results showed an increase in surface compressibility and a
      reduction in respreadability index in SM group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589931
TI  - Studies on the prenatal toxicity of 3-methyl-1-butanol and 2-methyl-1-propanol in
      rats and rabbits following inhalation exposure.
AB  - 3-Methyl-1-butanol (MEB) and 2-methyl-1-propanol (MEP) were tested for their
      prenatal inhalation toxicity in pregnant Wistar rats or Himalayan rabbits. Twenty
      five female rats and 15 female rabbits per group were exposed to MEB and MEP
      vapors at concentrations of 10, 2.5, or 0.5 mg/liter, 6 hr/day. The rats were
      exposed on Days 6-15 postcoitum (pc) and the rabbits were exposed on Days 7-19
      postinsemination (pi). Control groups were exposed to clean air. The body weights
      of the animals of either species were determined several times throughout the
      studies. All rats and all rabbits were killed on Day 20 pc and Day 29 pi,
      respectively. The fetuses were removed from the uterus and examined for compound
      related effects. The high concentration of 10 mg/liter caused a slight
      retardation of body weight gain in the dams of either species exposed to MEB and
      in the dams of rabbits exposed to MEP during the first days of the exposure
      period. Eye irritation was observed only in the MEB-treated rabbits during the
      period of exposure to 10 mg/liter. The fetuses of either species exhibited no
      signs of embryo-/fetotoxicity or teratogenic effects caused by MEP or MEB. Under
      the experimental conditions, 2.5 mg/liter was found to be a no-observable-adverse
      effect level (NOAEL) for the dams of either species exposed to MEB and for the
      does exposed to MEP, whereas 10 mg/liter MEP was the NOAEL for the maternal rats.
      For both substances 10 mg/liter was defined as the NOAEL for the conceptuses of
      either species.

PMID- 7589932
TI  - The reproductive and neural toxicities of acrylamide and three analogues in Swiss
      mice, evaluated using the continuous breeding protocol.
AB  - Acrylamide is a known genetic, reproductive, and neural toxicant, although it is
      not known if one effect is predominant. The toxicities of several structural
      analogues of acrylamide have been incompletely characterized, and the relative
      sensitivity of the second generation is not known. The present studies were
      designed to explore the relationship between neurotoxicity and reproductive
      toxicity, to further characterize the toxicities of three acrylamide analogues,
      and to evaluate the relative sensitivity of a second generation to these
      compounds. For the F0 generation, male and female Swiss CD-1 mice were provided
      drinking water containing acrylamide (ACR; 3, 10, 30 ppm), N,N'
      methylenebisacrylamide (MBA; 10, 30, 60 ppm), N-(hydroxymethyl)acrylamide (HMA;
      60, 180, 360 ppm), or methacrylamide (MACR; 24, 80, 240 ppm) during and after a
      14-week cohabitation. The last litter was reared and dosed after weaning until
      mating at 74 +/- 10 days of age with the same level of compound given to the
      parents Neurotoxicity was assessed at several times in both generations by
      measuring forelimb and hindlimb grip strength. In the F0 generation, ACR caused
      an 11% decrease in pup number without measurable neurotoxicity; female fertility
      was not affected. Although both generations consumed the same amount of ACR,
      there were larger changes in the fertility-related endpoints in the F1 mice than
      in the F0's, with no concomitant change in organ weights or sperm parameters. In
      F0 mice, MBA reduced the number of live pups and their adjusted weight, with no
      neurotoxicity and no change in F0 female reproduction. MBA caused greater adverse
      effects in the second generation, concomitant with increased consumption. In the
      F0 generation, HMA caused the largest decrease in pup number during cohabitation
      (26%) together with a small effect on grip strength. Female reproduction was not
      affected. The second generation consumed more HMA and showed slightly greater
      toxic effects. In both generations, MACR was negative for both neurotoxicity and
      reproductive toxicity. Dominant-lethal studies showed that the fertility effects
      for ACR, MBA, and HMA could be explained by a male-mediated increase in
      postimplantation loss. These studies found that dominant lethality occurred
      without structural effects on the reproductive system in the presence of only
      minor effects on grip strength and without detectable neural histopathology.
      Female reproduction was not significantly affected by these compounds at the
      doses used. Thus, these data confirm the male as the affected gender and that the
      reproductive toxicity was greater than motoneuron toxicity when measured as grip
      strength.

PMID- 7589933
TI  - An explanation on the limited efficacy of detoxication against VX toxicity by
      purified specific antibodies.
AB  - Studies on the mechanism of detoxication against VX toxicity by purified rabbit
      anti-VX antibodies were carried out in mice. VX (25 micrograms/kg) was injected
      subcutaneously immediately following intravenous injection of purified anti-VX
      antibodies. Blood concentration of free VX declined linearly as the antibody dose
      increased. Free VX concentration in brain was far lower than that in blood. When
      the dose of purified anti-VX antibodies was 8 and 6 mg/kg, respectively, free VX
      concentration in brain and blood approached 0. At the same time, the
      cholinesterase (ChE) activity in brain increased along with increasing antibody
      dose, with 70% of normal control value detected when 8 mg/kg antibodies were
      administered. On the other hand, anti-VX antibodies were not able to protect
      blood ChE unless the VX dose was lower than 10 micrograms/kg. The studies suggest
      that the protective action of purified rabbit anti-VX antibodies is from VX
      antibodies combining with the free VX in blood and extravascular tissue to reduce
      the amount of VX entering into the brain.

PMID- 7589934
TI  - A lifetime oncogenicity study in rats with acrylamide.
AB  - A lifetime oncogenicity study in Fischer 344 rats was conducted to accurately
      characterize the carcinogenic potency of acrylamide. Acrylamide was administered
      in drinking water throughout the 106-week study at concentrations required to
      provide a dose of 0, 0.1, 0.5, or 2.0 mg/kg/day to males or 0, 1.0, or 3.0
      mg/kg/day to females. Complete necropsy and gross pathology examinations were
      performed on all study animals. Histopathology examinations were conducted on
      selected tissues of all high-dose and control animals. Selected tissues from
      intermediate and low-dose groups were subjected to histopathological examinations
      as required to clarify high- and control-dose group observations. There was no
      visual observation of neurotoxicity in any study animal but sciatic nerve
      degeneration was observed in the male and female high-dose groups. Increased
      mortality related to acrylamide was observed in the high-dose male group from
      Month 17 to the end of the study and in the high-dose females during Month 24.
      Mesotheliomas of the testicular tunic were significantly increased in the high
      dose male group. The combined incidence of mammary gland adenocarcinomas and
      fibroadenomas was significantly increased in both acrylamide-dosed female groups.
      Males and females in the high-dose groups as well as females of the low-dose
      group had significantly (p < 0.001) increased thyroid follicular cell adenomas
      and adenocarcinomas. A variety of other tumor types observed with increased
      incidence in a previous acrylamide oncogenicity study (i.e., combined CNS glial
      neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and
      uterine adenocarcinomas) were not observed to be present at increased incidence
      in this study. This study confirms previously described acrylamide induction of
      benign tumors of the thyroid and mammary glands as well as mesotheliomas of the
      testis. By using a larger number of animals with an unbalanced study design, this
      study showed that acrylamide did not induce glial tumors and demonstrated that
      the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also
      demonstrated that the increased incidence of mammary tumors was again within
      historical control ranges.

PMID- 7589935
TI  - Use of X-rays in family practice. A multicentre study.
AB  - Practicing physicians, faced with pressure to control health care costs, are
      increasingly being asked to incorporate considerations of cost into their
      decisions regarding the care they offer their patients. Accordingly, it is of
      importance to know how the money is spent. The use and cost of X-rays in family
      practice, and what factors influence it, is not well known. The aim of this study
      is to analyse the use and the cost of X-ray requests in family practice. A
      prospective practice study from 16 Icelandic community health centres (HC) with
      computerised contact data and their target populations, 12 rural and four urban,
      was carried out. The X-ray requests, numbers, types and cost were analysed.
      Patient and practice characteristics were used to assess variation in X-ray
      practices. A total of 5173 X-ray requests were recorded, which comprised 3.2% of
      all office visits. The mean number of X-ray requests was 24.7 and 14.7/1000
      contacts in rural and urban HCs respectively, and 123.1/1000 inhabitants in rural
      HCs. The X-ray request rate per individual increased with age, but per contact it
      was highest among young males. Extremity and chest X-rays were the most common
      requests. For every 1000 individuals added to a practice population, the
      likelihood of having an X-ray requested decreased by 18%. The use of X-ray
      examinations in family practices represents approximately 17% of all ambulatory X
      ray use in Iceland. The calculated cost of X-rays requested in this study was
      $6157/1000 inhabitants per year as of October 1993.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7589937
TI  - The high vaginal swab in general practice: clinical correlates of possible
      pathogens.
AB  - Clinical features, diagnosis and treatment of 286 women whose high vaginal swabs
      (HVS) submitted by their general practitioners showed pure, heavy growth of
      Staphylococcus aureus, beta haemolytic streptococci groups A, C or G,
      Streptococcus milleri, Streptococcus pneumoniae or Haemophilus influenzae were
      analysed. Women with group A, C and G streptococci frequently had clinical
      vulvovaginitis and although the numbers were too small for statistical
      confirmation, S. pneumoniae and H. influenzae appeared to cause clinical disease
      as well. The association of S. aureus or S. milleri with clinical vulvovaginitis
      was much less convincing. It seems relevant for laboratories to report
      sensitivities for group A, C and G streptococci. Further research is needed to
      determine the pathogenicity of S. pneumoniae and H. influenzae.

PMID- 7589936
TI  - Can the Hospital Anxiety and Depression (HAD) Scale be used on Chinese elderly in
      general practice?
AB  - A study was carried out in a general practice in Hong Kong to find out if the
      Hospital Anxiety and Depression (HAD) Scale could be used to detect psychological
      problems in Chinese elderly. The HAD Scale was translated into Cantonese and
      administered by an interviewer to 298 Chinese aged 60 or above before their
      doctor consultations. The acceptance rate of the Scale was 96% and each interview
      took only 5-10 min to complete. All 298 elderly understood and completed the HAD
      Scale. Validation of the results of the HAD Scale by the Clinical Interview
      Schedule (CIS) was done on a random sample of 100 elderly. Relative operating
      characteristic (ROC) analysis showed that the optimal cut-off points of the HAD
      Scale was a depression score of 6 and an anxiety score of 3. The sensitivity was
      80%, specificity was 90%, OMR (overall misclassification rate) was 12%, positive
      predictive value was 67% and negative predictive value was 95%. Thirty-six per
      cent of the elderly had scores above these cut-off points. More females than
      males had high anxiety scores. Nearly half of those with positive HAD scores were
      not known to have any psychological illness. The HAD Scale has great potential to
      be used as a screening instrument for psychological illnesses in Cantonese
      speaking Chinese elderly all over the world.

PMID- 7589939
TI  - The use of hormone replacement therapy; results of a community survey.
AB  - Hormone replacement therapy is used for both menopausal symptoms and in
      prevention, but for the latter to be effective there may be a need to promote its
      use. Suitable strategies need to be informed by current practice. A postal
      questionnaire was therefore sent to 1649 women aged 20-69 years in Stockton-on
      Tees to assess which women consider and take hormone replacement therapy. The
      response rate was 74%. Therapy had been considered by 346 (28%) women of whom 164
      (47%) were premenopausal. It was taken by 20% of women aged 45-65 years. Users
      were more likely to have taken the contraceptive pill. Use of therapy by women
      with osteoporosis or cardiovascular disease, or with a family history of these,
      was low. As women used to the idea of taking hormone replacement therapy and
      accustomed to taking the contraceptive pill reach menopausal age there is likely
      to be an increase in uptake of therapy. By targeting the 'at risk' groups of
      women, the primary care team may be able to make most effective use of the
      therapy and their own resources for the prevention of osteoporosis and
      cardiovascular disease.

PMID- 7589938
TI  - Variability in GPs' referral rates in Spain.
AB  - The purpose of this study is to explore the causes that may influence the
      variations on referral rates in a sample of 242 general practitioners (GPs) in
      Spain. We applied Poisson multivariant regression modeling to analyze the role
      played by different variables related to doctors, patients and practices. The
      mean referral rate was 6.92 +/- 0.22 with a variant coefficient of 50.6%. The
      results of the Poisson model showed a statistically significant variation on the
      following variables: 1) doctor gender; 2) proportion of consultations to the
      practice made by male patients; 3) proportion of consultations made by patients
      over 65 years of age; 4) list size, 5) number of doctors in the PCT; 6) number of
      practice consultations to each doctor per week; 7) accredited practice for VT; 8)
      location of practice; 9) proportion of outpatient referrals; 10) proportion of
      private referrals; 11) proportion of emergency referrals; 12) proportion of
      referrals in which the patient's attitude did not influence the doctor for the
      referral; 13) proportion of new referrals. The statistical significance for the
      final model was very high (P < 0.00001). The study draws attention to the
      influence of some structural characteristics of health care system on the
      referral rates that could be modified to reduce the number of referrals from
      Primary to Secondary Care.

PMID- 7589940
TI  - Antibiotic use in upper respiratory tract infections in New Zealand.
AB  - Upper respiratory tract infections (URTIs) are a common reason for presentation
      to general practitioners. The current study used computerised consultation
      records of 100,222 patients from 17 general practices in New Zealand for the 12
      month period 1 July 1991-30 June 1992. URTIs were noted in 8.9% of all
      consultations: 44.1% of cases were children aged less than 10 years. Females
      presented more frequently than males for all ages above five years. Fifteen
      different antibiotics were prescribed for URTIs, but in 22.5% of cases no
      antibiotic was prescribed. There was no statistically significant difference in
      the likelihood of a successful outcome with or without antibiotic therapy (chi 2
      = 0.76, P > 0.05). The treatment failure profile of some antibiotics highlights
      the need for more prescriber education, especially as the range of medications
      available for general practitioner prescribing increases.

PMID- 7589942
TI  - Surviving the 'heartsink' experience.
AB  - The authors describe a pilot workshop designed to help doctors achieve a greater
      understanding of and ability to cope with their 'heartsink' patients.
      Participants were asked to list their personal objectives in attending and a
      number of cases were discussed in the group. A 'heartsink survival kit' was
      provided which consisted of skills and strategies which are useful in difficult
      consultations and an approach to reassessing the goals of the relationship which
      might promote a more realistic understanding. The workshop was videotaped and two
      scenarios are presented. The implications for further training are discussed.

PMID- 7589941
TI  - A pill for every ill?
AB  - Many doctors believe that Chinese expect a pill for every ill but this has never
      been validated by research data. The aim of our study was to find out what
      Chinese really expect from medications when they are ill. We interviewed a random
      sample of the 1068 Chinese in Hong Kong by telephone with a structured
      questionnaire. Only 40% thought illnesses always needed drug treatment but 76%
      always expected a prescription from a consultation. Nearly 100% of their last
      consultations resulted in a prescription. Eighty-five per cent of the
      prescriptions consisted of three drugs or more. Seven per cent of them thought
      too many drugs were given. Less than half of the people finished all the
      medications last prescribed. Those who thought too many drugs were given were
      less likely to have finished them. Younger age and more education were associated
      with less likelihood of thinking illnesses always needed drug treatment,
      consulting doctors for their last illnesses and expecting a prescription for
      every consultation. We conclude that Chinese do not expect a pill for every ill
      but doctors prescribe in nearly 100% of the consultations. Doctors may have over
      estimated Chinese patients' expectation for medications. They may even have
      created a high expectation for a prescription in every consultation through their
      own prescribing habit. More open discussion on the need and expectation for drugs
      between patients and doctors may help to make prescribing for Chinese patients
      more rational.

PMID- 7589943
TI  - No symptoms, no problem? Patients' understandings of non-insulin dependent
      diabetes.
AB  - Depth interviews were carried out with 46 people with non-insulin dependent
      diabetes. In the course of narrative accounts, respondents displayed their
      thinking about the nature of diabetes and their understandings of how one ought
      to respond to it. Two variations in patients' interpretations of diabetes are
      discussed here: the extent to which patients primarily orientated themselves
      toward symptom control or toward prevention of complications, and their
      perceptions of the seriousness of the condition. Most patients believed diabetes
      to be a serious condition, which could cause complications. However, many were
      able to reconcile such beliefs with a less than whole-hearted adherence to
      medical advice about lifestyle. The analysis suggests a range of specific areas
      of diabetes care where patients could be more fully informed. Most importantly it
      describes a range of ways in which patients present their non-adherence to
      medical advice about lifestyle as entirely rational, given their perceptions of
      diabetes and its personal implications for each of them. Better understanding of
      such perceptions by health professionals may improve therapeutic alliances.

PMID- 7589944
TI  - Patient expectations: what do primary care patients want from the GP and how far
      does meeting expectations affect patient satisfaction?
AB  - There is growing recognition of the importance of patients' expectations in
      general practice. This study aimed to investigate the types of expectations adult
      primary care patients have prior to consulting the GP, and how far meeting
      expectations is associated with increased satisfaction. Patients (n = 504)
      attending general practitioners (n = 25) at 10 London general practices were
      included in the study. The Patients Intentions Questionnaire (PIQ) was
      administered prior to the consultation to investigate patients' expectations and
      the Expectations Met Questionnaire (EMQ) was administered after the consultation
      to find out what the patient reportedly obtained. Satisfaction with the
      consultation was also measured using the Medical Interview Satisfaction Scale
      (MISS). The results of a principal components analysis of PIQ item scores
      indicated that the most wanted items were for 'explanation of the problem'. There
      was less desire for 'support' or 'tests and diagnosis'. Many of the 'support'
      items could potentially be provided to all patients, yet a proportion of patients
      reported not receiving these items from the GP. The results of one-way ANOVAs
      revealed that patients with greater numbers of their expectations met reported
      significantly higher satisfaction with the consultation than those with lower
      numbers met. The PIQ and EMQ could be potentially useful self-audit tools for use
      by general practitioners and trainee GPs.

PMID- 7589945
TI  - Situational disease.
AB  - The American sociologist Angelo Alonzo has put down the premises for a theory of
      illness behaviour based on an interactionist-situational framework. In this
      article I suggest that a disease concept of 'situational disease' based on this
      framework would be well suited for clinical work in general practice. The
      outlines of the theory is given and compared with a more traditional diagnostic
      model, especially with regard to consequences for treatment and research methods.
      I argue that there is a narrow relationship of disease models and research
      methodology and that e.g. a rigorous enforcement of the prevailing methodology of
      controlled clinical trials is liable to uphold an anachronistic disease model.
      Practice guidelines which originate from a situational understanding of disease
      should be encouraged and to this end general practice needs to develop a broad
      range of research methods suited to its distinctive professional role.

PMID- 7589946
TI  - Undergraduate medical students' rating of clerkship in general practice.
AB  - In recent years there has been an increasing demand for more involvement of
      general practice in undergraduate medical education. General practice and primary
      care can contribute with a relevant clinical content but also be a major resource
      in facilitating of professional development of the medical student. In the
      reformed undergraduate medical education of the Faculty of Health Sciences,
      University of Linkoping, Sweden, general practice has been given an important and
      extensive role. To evaluate the students' opinion on the recurrent clerkships in
      general practice a written questionnaire was given to all students after each
      clerkship. In the autumn of 1992, 74% of the 115 students answered this
      questionnaire. The questionnaire was focused on qualities regarded as important
      for creating the best educational milieu for the professional development of the
      student. Factor analysis of the different questionnaire headings showed a good
      construct validity. The distinct constituent elements were those of the clerkship
      structure, the amount of tutoring, and the student-tutor relationship. The
      students' overall satisfaction was high. It was not gender-related, nor did it
      fall with increasing semester stage. It was mainly determined by the qualitative
      clerkship and provider factors. The strongest of these was the 'quality of
      tutoring' whereas the 'quantity of tutoring' was weakest. Considering that the
      general practitioners were relatively inexperienced as educators, these results
      were both gratifying and promising, although they indicate a need for further
      improvement of the competence of the tutoring general practitioners.

PMID- 7589947
TI  - Illness and family functioning: theoretical and practical considerations from the
      primary care point of view.
AB  - The way in which the family copes with and adapts to illness of one of its
      members has a strong impact on the physical and psychosocial well-being of all
      members and on the shape and duration of the clinical course of the illness
      itself. The family doctor therefore should be able to evaluate the families'
      adaptation to illness and to promote successful coping strategies where
      necessary. This review illustrates how the family doctor's evaluation of the
      illness impact on family functioning is facilitated by a family developmental
      approach and by the use of a psychosocial classification scheme of illnesses.

PMID- 7589948
TI  - Computerised data collection: practicability and quality in selected general
      practices.
AB  - The objective of the study as to assess the consistency with which a set of pre
      defined data about three fictitious patients was entered into a sample group of
      practice computer systems, and to measure the time required for routine data
      capture of this kind. The study design was a prospective, piloted, postal survey,
      in which respondents were requested to enter a variety of general sample data
      onto their systems, to time the process, and record details of any difficulties.
      The subjects were 76 (39%) responding general practices in England and Ulster,
      from a random sample of members of a GP computer specialist group. These results
      (which in view of the highly motivated characteristics of the responding sample
      are likely to represent best practice) showed that differing conventions were
      applied in entering patient data, even among practices using the same type of
      computer system. Potentially significant errors and distortions were found in the
      data as recorded in the systems, such as the 29% of immunisation sequences which
      were slightly inaccurately entered. The main problems with the data entry
      comprised simple operator errors, inconsistency in the use of terms entered, and
      difficulties in recording negative data (only 20% of practices could enter
      patient 'not incontinent'). Practices varied widely in the way they allocated
      data recording responsibilities to staff, with only 6% of practices involving all
      staff in data entry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7589949
TI  - Reducing systematic bias in studies of general practitioners: the use of a
      medical peer in the recruitment of general practitioners in research.
AB  - Reducing systematic bias in any group of study participants should be a priority
      of any researcher. This can be achieved by ensuring the sampling framework is
      adequate and by increasing response rates. Response rates in studies of general
      practitioners have to date tended to be low. Generalization of results to the
      wider population of GPs is therefore reduced. This paper systematically examines
      those factors which can reduce bias, recognising accurate identification of the
      target population, gaining good access to respondents, and maximising response
      rates as crucial factors. The importance of a medical peer in recruitment is
      examined. Applying these factors to a study situation, three different
      recruitment strategies were tested. As the strategy improved, there was an
      incremental improvement in the response rate (44%, 67%, 78%). These results
      indicate that by specifically addressing strategies which facilitate access to
      the target population, and increase the legitimacy and credibility of the study,
      significant improvements in response rates can be achieved.

PMID- 7589950
TI  - Teenage pregnancy in the United Kingdom in the 1990s: the implications for
      primary care.

PMID- 7589951
TI  - Selections from current literature: the traveller to high altitude.
AB  - AMS is a preventable disease about which travellers are frequently uninformed and
      one which physicians may wrongfully assume is limited to the population of ultra
      high altitude adventurers. These studies on incidence, while not without flaws,
      point out the frequency of AMS, as well as its significant incidence at moderate
      and commonly frequented altitudes. The current literature does not fully answer
      questions about incidence at moderate altitudes, nor about the full effects of
      altitude on children. Certainly AMS is not a rare complication of travel to
      altitudes and may indeed be under-recognized and under-treated. Both
      acetazolamide and dexamethasone provide adequate prophylaxis, and the choice of
      medications can be to some extent based on experience and patient profile. The
      best prophylaxis is a slow stepwise ascent, and the best treatment descent. The
      availability of medications for the amelioration or prevention of symptoms, and
      succinct advice on prevention by travel planning will make many of our patients'
      holidays more enjoyable and business trips more productive.

PMID- 7589952
TI  - Association of University Departments of General Practice. 24th Annual meeting.
      July 1995. Abstracts.

PMID- 7589953
TI  - [Chronobiologic study of cardiac activity regulation in the course of urgent
      adaptation of healthy persons to high altitude conditions].

PMID- 7589956
TI  - [A picture of electrophoretic mobility of blood erythrocytes in patients during
      physical exertion and psychic stress].

PMID- 7589955
TI  - [Dynamics of objective audiometry parameters in liquidators of the accident at
      the Chernobyl nuclear power plant].

PMID- 7589954
TI  - [Thermoregulatory activity of motor units in newborns and in young children].

PMID- 7589958
TI  - [Electrophysiologic analysis of visual perceptive memory. I. Effect of interval
      duration between compared letters on parameters of event-related potentials].

PMID- 7589957
TI  - [CO2--a natural inhibitor of the generation of active species of oxygen in
      phagocytes].

PMID- 7589959
TI  - [Macro- and microrheologic properties of blood in people with varying levels of
      training].

PMID- 7589960
TI  - [Effect of T-activin and irradiation with a helium-neon laser on the status of
      the interleukin-2-dependent component of the proliferative response of
      mononuclear cells in rheumatoid arthritis].

PMID- 7589962
TI  - [Stimulating effect of cerebrospinal fluid from epileptic patients on the growth
      of neurites from sensitive neurons in tissue culture].

PMID- 7589961
TI  - [Effect of cerebrospinal fluid from patients with neuro-infections on explants of
      spinal ganglia].

PMID- 7589964
TI  - [Disorders of perception of stimulus intensity in peripheral involvement of the
      sound-perceiving apparatus].

PMID- 7589963
TI  - [Change in the perception of emotionally significant speech as affected by
      noise].

PMID- 7589965
TI  - [Role of cardiac and respiratory rhythms in mechanisms of counting time].

PMID- 7589967
TI  - [Changes in the functional state of the brain in children following a course of
      transcutaneous electric stimulation of the visual analyzer].

PMID- 7589968
TI  - [Correlations of brain potentials during various degrees of concentration of
      attention].

PMID- 7589966
TI  - [Reason for emergence of syncope during long diving].

PMID- 7589969
TI  - [Profile of functional interhemispheric asymmetry and EEG features of stuttering
      children].

PMID- 7589971
TI  - [Hemispheric asymmetry while learning of visual stimulus classifications under
      conditions of hindrance].

PMID- 7589970
TI  - [Effect of functional bio-regulation on the non-specific brain systems in
      children suffering from neurotic hyperkinesia].

PMID- 7589973
TI  - [Information model of adaptation development].

PMID- 7589972
TI  - [Phenomenology of spatial illusory reactions in weightlessness].

PMID- 7589975
TI  - [Autonomic correlates of the activity of a human computer operator in various
      levels of performance].

PMID- 7589974
TI  - [Degree of decrease in working capacity of operators as affected by various
      environmental factors].

PMID- 7589976
TI  - [Energy metabolism in school children operating a computer with various levels of
      success].

PMID- 7589977
TI  - [Perception and reproduction of time intervals in people with varying alpha- and
      beta-rhythm characteristics].

PMID- 7589978
TI  - [Correlation between specific oxygen consumption in the myocardium and myocardial
      mass in healthy people and in patients with heart defects].

PMID- 7589979
TI  - Educating the biomedical scientist.

PMID- 7589982
TI  - Structure and mechanism of the iron-sulfur flavoprotein phthalate dioxygenase
      reductase.
AB  - Transfer of electrons between pyridine nucleotides (obligatory two-electron
      carriers) and hemes or [2Fe-2S] centers (obligatory one-electron carriers) is an
      essential step mediated by flavins in respiration, photosynthesis, and many
      oxygenase systems. Phthalate dioxygenase reductase (PDR), a soluble iron-sulfur
      flavoprotein from Pseudomonas cepacia, is a convenient model for the study of
      this type of electron transfer. PDR is folded into three domains; the NH2
      terminal FMN binding and central NAD(H) binding domains are closely related to
      ferredoxin-NADP+ reductase (FNR). The COOH-terminal [2Fe-2S] domain is similar to
      plant ferredoxins, and can be removed by proteolysis without significantly
      altering the reactivity of the FNR-like domains. Kinetic studies have identified
      sequential steps in the reaction of PDR with NADH that involve pyridine
      nucleotide binding, hydride transfer to FMN, and intramolecular electron transfer
      from the reduced flavin to the [2Fe-2S] cluster. Crystal structures of reduced
      and liganded PDR correspond to some of the intermediates formed during reduction
      by NADH. Small structural changes that are observed in the vicinity of the
      cofactors upon reduction or NAD(H) binding may provide part of the reorganization
      energy or contribute to the gating mechanism that controls intramolecular
      electron transfer.

PMID- 7589980
TI  - Liver regeneration.

PMID- 7589985
TI  - Glycosyltransferase mutants: key to new insights in glycobiology.
AB  - Glycosyltransferases (Glyc-T's) catalyze the synthesis of the carbohydrate
      portions of glycoproteins, glycolipids, and proteoglycans. Most Glyc-T's transfer
      one sugar in one linkage and are encoded by a unique gene. Thus, synthesis of a
      branched carbohydrate may require expression of at least 30 Glyc-T genes.
      Mutations that alter Glyc-T activity therefore provide an approach to identifying
      functions for carbohydrates. These fall into two general categories: 1)
      intramolecular functions pertaining to the physical and biochemical properties of
      a glycoconjugate; and 2) intermolecular functions that involve recognition of
      sugar (or sugars) by another molecule, such as the selectins that bind to
      specific sugar sequences at the cell surface. In this review, the origin, nature,
      and uses of Glyc-T mutants that have been used to study both types of
      carbohydrate function will be summarized. Many Glyc-T genes are now cloned, so
      transgenic and gene disruption techniques are the latest strategies for
      identifying new functions for carbohydrates. It is already apparent that the
      consequences of altering the spectrum of carbohydrates expressed by a cell or an
      organism range from "none" to "death." A key challenge for the future is to
      identify molecular bases for the complex phenotypes created by glycosylation
      engineering. Equally important will be to understand factors that regulate Glyc-T
      genes, a new class of genes whose study may reveal novel mechanisms of biological
      regulation.

PMID- 7589981
TI  - The extracellular matrix in hepatic regeneration.
AB  - After partial hepatectomy, as a consequence of hepatocyte proliferation, cell
      clusters containing 10-14 hepatocytes are formed. These clusters are devoid of
      sinusoids and extracellular matrix; therefore, many hepatocytes are two to three
      cells removed from the vascular spaces. Four days after hepatectomy, Ito cells
      send delicate cell processes between the hepatocytes in the clusters. This
      "invasion" of the clusters coincides with the activation in Ito cells of genes
      encoding for several laminin chains. The penetration of Ito cells into the
      clusters is followed by fenestrated endothelial cells, and in this manner the
      normal hepatocyte vascular relationship is restored. As soon as the normal
      vascular structure is reestablished, the laminin genes are turned off. This chain
      of events is similar to the one taking place during hepatogenesis when continuous
      capillaries are converted into sinusoids. This similarity in hepatogenesis and
      regeneration suggests that the secreted laminin chains may be signals for the
      vascularization of the clusters by fenestrated sinusoids. During this process
      neither entactin nor laminin alpha chains are secreted. The vascularization of
      the regenerating clusters contrasts sharply to the vascularization of cirrhotic
      nodules. In the latter case, entactin and perhaps laminin alpha 1 chains are
      secreted, and the final result is the formation of basement membranes and
      continuous capillaries rather than fenestrated sinusoids. We suggest that
      entactin and specific laminin chains play a crucial role in determining the
      outcome of hepatic injury. Definition of the roles of entactin and laminin chains
      in vascularization and modulation of the endothelial phenotype will not only
      elucidate important aspects of regeneration, but may provide a better
      understanding of cirrhosis and even suggest therapeutic approaches.

PMID- 7589984
TI  - How are class II MHC genes turned on and off?
AB  - Fragments of foreign antigen are detected by CD4+ helper T cells via the T cell
      receptor for antigen in the context of major histocompatibility complex (MHC)
      class II molecules. Very few cells normally express class II MHC molecules, and
      these cells play critical roles in antigen presentation and in the thymic
      selection of T lymphocytes before their exit into the periphery. Because of the
      central role the class II MHC molecules play in immune system function, it is not
      surprising that the lack of expression of these molecules results in a severe
      combined immunodeficiency disorder (called bare lymphocyte syndrome) and that the
      aberrant expression of the molecules is frequently observed in the target organs
      of various autoimmune disorders (e.g., multiple sclerosis and rheumatoid
      arthritis). Because both classes of disease could conceivably be treated by
      molecular approaches targeted at either restoring or inhibiting expression of
      class II MHC genes, there has been an intense effort during the past decade to
      elucidate the regulatory mechanisms of class II MHC genes. An analysis of recent
      advances in this effort is provided in this review article.

PMID- 7589983
TI  - The RNA polymerase II elongation complex.
AB  - The initiation stage of transcription by RNA polymerase II has long been regarded
      as the primary site for regulation of eukaryotic gene expression. Nevertheless, a
      growing body of evidence reveals that the RNA polymerase II elongation complex is
      also a major target for regulation. Biochemical studies are implicating an
      increasing number of transcription factors in the regulation of elongation, and
      these transcription factors are being found to function by a diverse collection
      of mechanisms. Moreover, unexpected features of the structure and catalytic
      mechanism of RNA polymerase II are forcing a reconsideration of long-held views
      on the mechanics of some of the most basic aspects of polymerase function. In
      this review, we will describe recent insights into the structures and functions
      of RNA polymerase II and the transcription factors that control its activity
      during the elongation stage of eukaryotic messenger RNA synthesis.

PMID- 7589986
TI  - Coated vesicles: a diversity of form and function.
AB  - In every well-characterized example, the small transport vesicles that mediate
      membrane trafficking between intracellular organelles are encased in a protein
      coat. In general, the coat proteins assemble from cytosolic pools onto the
      membrane and play a critical role in vesicle formation. Recent reviews have
      emphasized the clear similarities in the mechanisms that drive vesicle budding at
      distinct cellular locations. Here we focus on the diversity of solutions to an
      apparently related biological task. These mechanistic differences are likely to
      be physiologically important determinants of the diversity in form, and function
      of coated transport vesicles.

PMID- 7589987
TI  - Actions of anesthetics on ligand-gated ion channels: role of receptor subunit
      composition.
AB  - Molecular cloning of cDNAs coding for ligand-gated ion channel subunits makes it
      possible to study the pharmacology of recombinant receptors with defined subunit
      compositions. Many laboratories have used these techniques recently to study
      actions of agents that produce general anesthesia. We review the effects of
      volatile and intravenous anesthetics on recombinant GABAA, glycine, AMPA,
      kainate, NMDA, and 5HT3 receptors. Evidence for and against specific ligand-gated
      ion channel subunits as targets responsible for anesthesia or the side effects of
      anesthetic agents is discussed for each type of receptor. Subunit specific
      actions of some of the agents suggest that construction and testing of certain
      chimeric receptor subunits may be useful for defining the amino acid sequences
      responsible for anesthetic actions.

PMID- 7589988
TI  - Mechanisms of calcium oscillations and waves: a quantitative analysis.
AB  - Oscillations and waves of increased intracellular free calcium concentration
      ([Ca2+]i) are observed in a wide range of cell types. Because of their inherent
      nonlinear nature and the consequent unreliability of intuitive approaches,
      mathematical modeling has an important role to play in the study of these
      phenomena. One important class of oscillations and waves is dependent on the
      presence of inositol (1,4,5)-trisphosphate (IP3), which releases Ca2+ from
      internal stores via the IP3 receptor/Ca2+ channel. With the minimum possible
      mathematical formalism, we review mechanistic models for IP3-dependent Ca2+
      oscillations and waves. These models are based on the regulation of the IP3
      receptor by both IP3 and Ca2+, and incorporate experimental data on the steady
      state and kinetic properties of the receptor. The extension of the models to
      describe intracellular and intercellular Ca2+ waves is considered.

PMID- 7589989
TI  - Stimulation of matrix metalloproteinase-dependent migration of T cells by
      eicosanoids.
AB  - Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), at nanomolar to micromolar
      concentrations, elicited migration of human blood T cells and cultured T
      lymphoblastoma cells of the Tsup-1 line through a layer of Matrigel basement
      membrane matrix. The density of Tsup-1 cell high-affinity receptors was low for
      PGE2 and high for LTB4, resulting in respectively predominant chemokinetic and
      chemotactic stimulation of migration. Migration-enhancing concentrations of PGE2
      and LTB4 also increased Tsup-1 cell content and secretion of matrix
      metalloproteinases (MMPs) 2, 3, and 9, which were quantified by Western blots and
      zymography, and augmented Tsup-1 cell-surface expression of the MMPs, as shown by
      flow cytometry. That a specific MMP inhibitor suppressed migration of blood T
      cells and Tsup-1 cells through Matrigel, but did not affect PGE2- and LTB4
      initiated T cell migration through micropore filters without Matrigel, suggests
      dual requirements for MMP expression and enhanced motility in T cell passage
      through basement membranes.

PMID- 7589990
TI  - Modulation of cardiac physiology by an anti-Trypanosoma cruzi monoclonal antibody
      after interaction with myocardium.
AB  - Circulating antibodies from human and murine chagasic sera are able to interact
      with myocardium, activating neurotransmitter receptors. Here, we studied the
      effects of a monoclonal antibody (MAb CAK20.12), which recognizes a 150
      kilodalton antigen of Trypanosoma cruzi and reacts with normal human and murine
      striated muscles and with cardiac tissue. The MAb CAK20.12 binds to purified
      cardiac membranes and interferes with the binding of beta-adrenergic receptor
      radioligand ([125I]CYP) and muscarinic cholinergic receptor (mAChR) radioligand
      ([3H]QNB) in a noncompetitive way. As a consequence of this interaction, beta
      adrenergic receptor and mAChR were activated, leading to increased intracellular
      levels of cyclic AMP as a result of beta-adrenergic receptor-coupled adenylate
      cyclase triggering. When its sympathetic action was abrogated, it also induced an
      mAChR-mediated increase in cyclic GMP. Furthermore, cardiac physiology was
      modified by MAb CAK20.12, as it was able to increase cardiac contractility
      through beta-adrenoceptor activation and to decrease atrial frequency as a result
      of mAChR activation. The fact that this MAb modulates and modifies the mechanical
      and biochemical activity of normal murine heart established an important basis
      for future research and understanding of how the host's humoral immune response
      acts on the course and development of the chronic chagasic myocardiopathy.

PMID- 7589993
TI  - Mercury in dental amalgam.

PMID- 7589991
TI  - Identification of a renal cell line that constitutively expresses the kidney
      specific high-affinity H+/peptide cotransporter.
AB  - In this study we describe for the first time the identification of a renal cell
      line that expresses the kidney-specific high-affinity H+/peptide cotransport
      system. The kidney cell line SKPT-0193 C1.2 was obtained by SV40 transformation
      of rat proximal tubular cells. The transport of the dipeptide glycylsarcosine
      (Gly-Sar) was studied in this cell line grown as a confluent monolayer on
      impermeable plastic supports. Uptake of the dipeptide was rapid and was
      stimulated sixfold by an inwardly directed H+ gradient, with optimal uptake
      occurring at an extracellular pH of 6.0. The uptake was markedly reduced by the
      protonophore carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone whether
      measured at pH 7.5 or 6.0. Intracellular acidification of the cells by NH4Cl
      prepulse also reduced the uptake of glycylsarcosine. The dipeptide uptake was
      found to be mediated by a high-affinity transport system with a Michaelis-Menten
      constant (Kt) of 67 +/- 2 microM and a maximal transport velocity of 1.20 +/-
      0.02 nmol.10 min-1.mg protein-1. Studied over a concentration range of 5 microM
      to 5 mM, there was no evidence for a second saturable transport component. Di-
      and tripeptides, but not glycine, were strong inhibitors of glycylsarcosine
      uptake, indicating that these peptides also interact with the transport system
      with high affinity. Northern blot analysis of poly(A)+RNA from these cells using
      cDNA probes specific for the human intestinal peptide transporter (PEPT 1) or the
      human kidney-specific peptide transporter (PEPT 2) revealed that the transport
      system expressed in these cells is PEPT 2. It is concluded that the SKPT-0193
      C1.2 cell line constitutively expresses the kidney-specific high-affinity
      H+/peptide cotransporter described in the proximal tubular epithelial cells of
      the normal kidney.

PMID- 7589994
TI  - The peer reviewer should be fair--secret or otherwise.

PMID- 7589995
TI  - The perils of eating.

PMID- 7589996
TI  - [P53 protein: a new tool for the clinician?].

PMID- 7589998
TI  - [Overexpression of protein p53 and Barrett esophagus. A frequent and early event
      in the course of carcinogenesis].
AB  - OBJECTIVES AND METHODS: In Barrett's oesophagus, the risk of malignancy is
      evaluated histologically with the presence of dysplasia. The abnormal expression
      of p53 protein could represent a useful new marker. The aim of this study was
      evaluate the abnormal expression of p53 protein in a series of 52 oesophagectomy
      specimens with Barrett's oesophagus, either non-dysplastic (n = 3), dysplastic (n
      = 8), or malignant (n = 41). The immunohistochemical study was made on
      deparaffinized sections with the monoclonal anti-p53 antibody DO7. RESULTS: The 3
      non-dysplastic cases were p53 negative; 1 case of low-grade dysplasia in 5 was
      positive, as were the 3 cases of high grade dysplasia and 33 of 41 cancers (80%),
      including 13 superficial cancers in 14 (93%) and 20 invasive cancers in 27 (74%).
      A common feature was the presence of rare p53 positive crypts in low grade
      dysplastic areas and non-dysplastic specialized mucosa that surrounded high grade
      dysplasia and cancers. CONCLUSIONS: Our results confirm the high frequency of the
      abnormal expression of p53 protein in cancer developed in Barrett's oesophagus.
      This expression is a consequence of alterations of the TP53 gene, and has an
      important role in the carcinogenesis of Barrett's mucosa; it is likely to
      represent an early event. Prospective studies are needed to evaluate its interest
      in the surveillance of patients with Barrett's oesophagus.

PMID- 7589992
TI  - Fifty years ago: the state of biochemistry.

PMID- 7589997
TI  - [Multivariate analysis of the prognostic and predictive factors of response to
      concomitant radiochemotherapy in epidermoid cancers of the esophagus. Value of
      immunodetection of protein p53].
AB  - OBJECTIVE: The purpose of this study was to determine the prognostic value of the
      expression of protein p53, EGF receptors (EGR-R), cell proliferation antigen
      (Ki67) and DNA analysis by flow cytometry on per-endoscopic biopsies as well as
      the ability of these factors to predict response to concomitant chemoradiation in
      patients with squamous cell oesophageal carcinoma. METHODS: Sixty-two patients
      with squamous cell oesophageal carcinoma were prospectively included in this
      study. For 58 patients (51 men, 7 women; mean age: 59.1 +/- 9.3 years), clinical
      response to chemoradiation was correlated with the findings of flow cytometry
      (ploidy, % of cells in S-phase) and immunohistochemistry (p53, EGF-R, Ki67).
      There were 4 patients in stage I, 14 in stage II, 27 in stage III, and 13 in
      stage IV. Chemoradiation (2 cycles associating continuous 5FU 800 mg/m2/24 h from
      D1 to 5 and from D22 to 26, Cisplatyl 70 mg/m2 on D1 and D22; 15 Gy/5d from D1 to
      5 and from D22 to 26), was performed prior to surgery in 19 patients (group I)
      and as the only treatment in 39 patients (group II), with a third cycle from D43.
      Clinical response was defined as complete or incomplete, ascertained by endoscopy
      and biopsy, 2 to 3 weeks after the end of chemoradiation. RESULTS: Mean survival
      in all 58 patients was 13.0 months. Survival was significantly longer in
      responders than in non responders (14.7 vs 9.6 months; P = 0.03). Among M0
      patients, survival was not different in case of exclusive chemoradiation therapy
      or chemoradiation therapy followed by surgical excision (17.6 vs 13.0 months;
      NS). Monofactorial analysis showed that, in addition to response, the variables
      related to survival were stage, non-metastatic status, and absence of p53
      surexpression. After multifactorial analysis according to the Cox model, the
      remaining variables were non-metastatic status, and absence of p53 surexpression.
      A complete response with negative biopsies was observed in 39 out of 58 patients,
      i.e. 67.3 +/- 12.1 % (group I: 12 out of 19; group II: 27 out of 39; NS).
      According to monofactorial analysis, 3 factors were predictive of complete
      response, i.e. non surexpression of p53 (P < 0.05) and tumour diameter (P =
      0.04). After step-by-step logistic regression, non surexpression of p53 and
      tumour diameter continued to be predictive. The relative risk of a non-complete
      response was 5.46 if p53 was detected and 1.84 for each cm of added tumour
      diameter. These two factors were independent. CONCLUSIONS: In this study the
      predictors of complete response were absence of p53 surexpression and tumour
      diameter ascertained by CT-scan. Flow cytometry and Ki67 antigen had no
      prognostic value and were not predictors of response.

PMID- 7589999
TI  - [Comparison of the cost-efficacy ratio of omeprazole and ranitidine in the
      treatment of reflux esophagitis].
AB  - OBJECTIVE: The objective of this study was to compare the cost of achieving a
      unit of clinical success for treatment of reflux oesophagitis with either
      ranitidine or omeprazole. METHODS: After randomisation 430 patients with reflux
      oesophagitis (grade 2 or 3) were assigned to receive omeprazole 20 mg or
      ranitidine 150 b.i.d. for 8 weeks. Patients were given diary cards to assess
      their symptoms every day, and record every two weeks a life satisfaction index.
      Patients were seen after 4 and 8 weeks for symptoms assessment and repeat
      endoscopy at 8 weeks. The perspective of the analysis was that of the payer. The
      costs of medical care were based in French drug costs currently advertised,
      payment for physician and actual mean payment for upper GI endoscopy. RESULTS:
      The healing rates at 8 weeks in the omeprazole group and the ranitidine group
      were 93 and 67.5% respectively. After 8 weeks of treatment, life satisfaction was
      good in 81 and 53.6% and the relief of pain was 86,6 and 69,5% respectively. For
      each effectiveness criteria, omeprazole was more cost effective than ranitidine:
      cost per healed patient (2,338 F vs 2,744 F), cost per asymptomatic patient
      (2,510 F vs 2,964 F), cost per patient with a good or very good life satisfaction
      index (2,687 F vs 3,456 F). This advantage remained independent of the
      oesophagitis initial severity. The sensitivity analysis showed that the results
      were unsensitive to the variations of the efficacy variables in their confidence
      interval. CONCLUSIONS: This cost-effectiveness analysis suggests that in the
      treatment of reflux oesophagitis, the strategy with the more effective treatment
      is more cost-effective.

PMID- 7590001
TI  - [Cyclosporine A and chronic inflammatory diseases of the digestive tract].

PMID- 7590000
TI  - [Effect of C-terminal derivatives of sorbin on duodenal ion transports in rats].
AB  - OBJECTIVES AND METHODS: Synthetic derivatives of sorbin have been shown to
      inhibit VIP stimulated fluxes in the ileum in decreasing plasma-to-mucosa Na and
      Cl effluxes. The effect of this group of new peptides, without homology with any
      known peptides, was determined in rat duodenum where ion transport mechanisms
      differ. The improved technique of ligated loops in situ, was used, permitting the
      simultaneous measurement of net fluxes, influxes and effluxes for Na and Cl, in
      an integrated in vivo model. To determine the minimal active fragment of sorbin,
      synthetic C5, C7 and C20 peptides were tested and compared with known anti
      secretor drugs such as loperamide, neuropeptide Y, somatostatine and
      metenkephalinamide. RESULTS: C7-sorbin was the minimal peptide able to decrease
      duodenal VIP-stimulated fluxes of water, Na and bicarbonate. It intervenes in
      increasing Na influx and more slightly Cl influx, which have been decreased by
      VIP. It does not modify much Na and Cl effluxes stimulated by VIP. Sorbin effect
      is in contrast with those of known antidiarrheic agents like somatostatine,
      loperamide, NPY and metenkephalinamide which chiefly decrease Cl efflux.
      CONCLUSIONS: Sorbin acts like an activator of absorption in the duodenum, in
      contrast to the other peptides or drugs and to its own anti-secretor effect in
      the ileum.

PMID- 7590002
TI  - [Hepatic peliosis, a still current disease].

PMID- 7590003
TI  - [Chronic viral hepatitis C. Anatomoclinical and biological correlations].
AB  - OBJECTIVES: The relations between the severity of histopathological lesions and
      epidemiological, clinical and biological data were studied in 86 patients with
      chronic viral hepatitis C. PATIENTS AND METHODS: None of the patients had any
      clinical signs of decompensated liver disease. Three groups of patients were
      individualized according to histopathological findings: 17 (20%) had chronic
      persistent hepatitis, 48 (56%) had chronic active hepatitis without cirrhosis,
      and 21 (24%) had cirrhosis. RESULTS: Patients with cirrhosis differed
      significantly from patients in the two other groups for all biological
      parameters. With multivariate analysis, alkaline phosphatase activity and serum
      hyaluronic acid were two independent parameters significantly associated with
      cirrhosis. A serum hyaluronic acid level above 150 micrograms/L or alkaline
      phosphatase activity above normal were predictive of cirrhosis with a sensitivity
      of 87% and a specificity of 93%. None of the parameters in this study provided a
      clear distinction between patients with chronic persistent and chronic active
      hepatitis. CONCLUSION: Determination of serum hyaluronic acid and alkaline
      phosphatase activity as a non invasive index of cirrhosis could be useful for
      diagnosis and follow-up in patients with chronic viral hepatitis C.

PMID- 7590004
TI  - [Efficacy and tolerance of praziquantel (Biltricide) in the treatment of
      distomatosis caused by Fasciola hepatica].
AB  - OBJECTIVES: Due to the side-effects of dehydroemetine, we have chosen
      praziquantel, a broad-spectrum antihelmintic, as a treatment for distomatosis
      secondary to Fasciola hepatica in humans. The aim of this retrospective study was
      to evaluate the efficacy and tolerance to praziquantel in patients with this
      disease. METHODS: Twenty-five patients (12 men) with a definite diagnosis of
      distomatosis and no previous treatment were followed-up between 8 months and 3
      years (> 18 months in 76% of cases). The follow-up was based on clinical,
      biochemical and serological criteria. All patients received praziquantel (75
      mg/kg/day orally) for 5 days. Treatment was started after endoscopic or surgical
      removal of parasites locolized in the biliary tract, in two patients. A similar
      therapeutic course was administered twice in four patients with persistent
      clinical symptoms, hypereosinophilia or arch 2 on immunoelectrophoresis. RESULTS:
      Cumulative rates of patients with normalized eosinophilia and seronegativation at
      6, 9 and 12 months were 55, 65, 75% and 55, 70, 100%, respectively. Complete
      recovery occurred in 18 patients (72%) whereas hypereosinophilia persisted for
      more than one year in 5 patients. No side-effects, except transient nausea in a
      few cases, were observed. CONCLUSION: Since praziquantel seems to be both
      effective and well tolerated in a large proportion of patients, this drug can be
      recommended as a first choice for distomatosis due to Fasciola hepatica in human.

PMID- 7590006
TI  - [What are the non transfusional modes of transmission of hepatitis C virus?].

PMID- 7590010
TI  - [Uveitis complicating celiac disease and cured by gluten-free diet].

PMID- 7590007
TI  - [Multiple carcinoid tumors of the small intestine].
AB  - Multiple carcinoid tumours of the small bowel with more than 3 lesions are very
      unusual. We report a case of a 44-year-old man who presented with more than 40
      carcinoid tumours localized in the ileum, associated with hepatic metastases and
      carcinoid tricuspid valve involvement. The site of the primary tumour was not
      determined by usual imaging techniques. The patient underwent laparotomy in order
      to resect liver metastases. The diagnosis of multiple carcinoid tumours of the
      small bowel was made during the abdominal exploration. There was no
      intraepithelial endocrine cell hyperplasia in the mucosa adjacent to the small
      bowel tumours. After a 6-month follow-up, the carcinoid syndrome had completely
      disappeared.

PMID- 7590005
TI  - [Interactions between chronic viral hepatitis C and pregnancy].
AB  - OBJECTIVES AND METHODS: In France, the positive rate for unit-HCV antibodies in
      the sera of pregnant women is usually found to be between 0.7 and 3.9%. The aim
      of our prospective study was to determine the interactions between pregnancy and
      chronic viral hepatitis C in 12 pregnant women. RESULTS: In our study, chronic
      viral hepatitis C did not influence maternal or neonatal outcome. The mean
      gestational age was 38.4 +/- 3 weeks. During follow-up, mean serum ALT levels
      were significantly lower (36 +/- 17 mU/mL) during the last three months of
      pregnancy compared to before pregnancy (237 +/- 144 mU/mL, P < 0.002) and after
      pregnancy (141 +/- 62 mU/mL, P < 0.0005). During the third trimester, serum ALT
      levels were normal in 90% of the women. However, the persistence of viremia
      during pregnancy and a rebound in serum ALT during the post-partum period have
      been noticed. CONCLUSION: The normalization of serum ALT levels during pregnancy,
      the persistence of viremia, and a rebound in serum ALT during post-partum could
      be related to pregnancy-induced changes in the immune system.

PMID- 7590009
TI  - [Delayed increase of serum gastrin level during prolonged treatment with
      omeprazole: two cases].

PMID- 7590008
TI  - [Peliosis hepatitis during intestinal lymphomatous polyposis treated with
      chemotherapy and radiotherapy. Regression after antibiotic therapy].
AB  - We report a case of regressive peliosis hepatis, which occurred in a 55 year-old
      woman with diffuse intestinal lymphomatous polyposis in remission after treatment
      with chemotherapy and radiotherapy, and which was cleared after one month
      treatment with erythromycin. The Warthin-Sarry stain, performed to identify a
      specific agent such as Rochalimaea quintana and henselae, was negative, and the
      polymerase chain reaction technique could not be performed. Regressive cases of
      peliosis hepatis are rare, and 4 out of 7 have been reported after antibiotic
      treatment. Two of them were observed after an antibiotic regimen with
      erythromycin in patients with HIV disease, and the bacilli Rochalimaea quintana
      and henselae were identified in liver tissue with Warthin-Starry stain and
      polymerase chain reaction technique. The observation and the regressive cases
      recently reported elsewhere, suggest that appropriate antibiotic treatment should
      be proposed when peliosis hepatis occurs.

PMID- 7590012
TI  - [Pseudomembranous colitis probably caused by Clostridium difficile: first case
      appeared during preventive treatment of infection of ascitic fluid with
      norfloxacin].

PMID- 7590013
TI  - [Familial congenital short pancreas].

PMID- 7590011
TI  - [Ileal malabsorption of vitamin B12 in the chronic alcoholics].

PMID- 7590014
TI  - [Endoscopy of the upper digestive tract by nasal approach: preliminary study with
      a pediatric endoscope].

PMID- 7590015
TI  - [Hepatic tuberculosis simulating a pyogenic abscess].

PMID- 7590018
TI  - [Pseudotumoral form of sarcoidosis].

PMID- 7590016
TI  - [Biliary ileus: simultaneous treatment of the occlusion and the biliary tracts].

PMID- 7590017
TI  - [Guillain-Barre syndrome in a patient with chronic active hepatitis C].

PMID- 7590019
TI  - [Place of endoscopy in the diagnosis and treatment of biliary complications after
      laparoscopic cholecystectomy].

PMID- 7590020
TI  - [Treatment of tumoral stenoses of the hepatic hilum].

PMID- 7590023
TI  - [Portal thrombosis and liver cirrhosis. Value of ultrasound-guided puncture
      biopsy of the thrombus].
AB  - OBJECTIVES AND METHODS: Portal vein thrombosis which occurs in the course of
      cirrhosis, associated or not with hepatocellular carcinoma, can be either cruoric
      or neoplastic. The aim of this study was to assess the feasibility and the
      results of ultrasound guided biopsy of portal vein thrombosis in 21 patients with
      cirrhosis (20 men and 1 woman; mean age 66 +/- 9 years), who were hospitalized
      between May 1989 and November 1993. Ultrasound guided biopsies of the cirrhotic
      liver, of the portal vein thrombosis and, when present, of a hepatic nodular
      lesion were performed. The diagnosis of hepatocellular carcinoma was made if the
      histological examination of the hepatic and portal biopsy samples were positive
      or if serum concentrations of alpha-fetoprotein were higher than 500 IU/mL.
      RESULTS: All portal vein thrombosis biopsies were successfully performed. No side
      effects were observed. Before ultrasound guided biopsy of the portal thrombosis,
      diagnosis of hepatocellular carcinoma was made in 15 cases, and diagnosis of
      cirrhosis in 6 cases. After histological examination of the portal sample,
      hepatocellular carcinoma was diagnosed in 19 cases and cirrhosis in 2 cases.
      Thus, in 19% of cases, ultrasound guided biopsy of the portal thrombus provided a
      definitive diagnosis. CONCLUSION: Ultrasound guided biopsy of the portal vein
      thrombosis must be performed before liver transplantation for cirrhosis or
      hepatocellular carcinoma to exclude the presence of a vascular neoplastic
      extension.

PMID- 7590025
TI  - [The GCB-Glaxo prize for the DEA continues its support of research].

PMID- 7590024
TI  - [Alagille syndrome in 1995. Clinical and genetic data].

PMID- 7590022
TI  - Flumazenil therapy for hepatic encephalopathy. A double-blind cross over study.
AB  - OBJECTIVES AND METHODS: Thirty-one patients with acute or chronic liver disease
      were included in the study to investigate the effect of flumazenil on hepatic
      encephalopathy. After screening for recent benzodiazepine use or non-hepatic
      causes of encephalopathy, 18 patients entered a double-blind cross-over study.
      The 13 remaining patients, most of them with renal failure or recent use of
      benzodiazepines, were given flumazenil in an open study. In the controlled study,
      flumazenil (1.0 mg) or placebo was given in a single injection on two separate
      days to study the immediate effect; half the patients received a continuous
      infusion of flumazenil (0.25 mg/h) or placebo for two 3-day periods to study a
      potential steady state effect. In the open study, a single bolus of flumazenil
      (1.0 mg) was given. RESULTS: In the controlled study, fifteen minutes after bolus
      injection, the clinical grade of hepatic encephalopathy decreased in 6 patients
      after injection of flumazenil, whereas a decrease was found in 2 after the
      placebo (P = 0.06). However, the EEG grade did not change in any of the patients,
      and the changes in the mean dominant frequency as measured by spectral analysis
      did not differ between flumazenil and the placebo. Furthermore, patients on
      flumazenil did not differ significantly from those on placebo during the infusion
      period. Subgroup analysis of underlying liver disease and the causes of
      encephalopathy revealed a trend for clinical improvement only in the patients
      with chronic liver disease, but without significant changes in the mean dominant
      frequency. In the open study, the clinical grade of encephalopathy decreased in 3
      patients and, in contrast to the controlled study, the EEG also improved in 2
      patients and the mean dominant frequency increased significantly. Responders had
      previously used benzodiazepines. CONCLUSION: Our study does not support a major
      therapeutic effect of flumazenil on hepatic encephalopathy.

PMID- 7590026
TI  - [Post-surgical or traumatic anal incontinences. Prospective study in 40 patients
      explorated by endorectal ultrasonography and electromyography].
AB  - OBJECTIVES: Anal endosonography is used to assess anal canal structure and
      external anal sphincter. The purpose of this study was to compare findings at
      anal endosonography with electromyographic tests in patients with faecal
      incontinence. METHODS: Fourty patients (31 women; median age: 47 years) were
      referred for exploration of the anal sphincter: 15 patients had previous anal
      surgery, 16 patients had obstetrical trauma, 3 patients had accidental trauma, 6
      women had obstetrical trauma and previous anal surgery. RESULTS: Anal
      endosonography demonstrated an external sphincter defect in 19 patients (partial
      n = 4, complete n = 15); 18 of these patients had an electromyographic study: an
      external sphincter defect was demonstrated by mapping in 15 cases; 3 partial
      defects were not found. Eight patients had associated pudendal nerve terminal
      motor latency delayed due to neuropathic impairment of pudendal nerve. Surgery
      was performed in 12 patients; external sphincter lesion was confirmed in all
      cases. CONCLUSIONS: Anal endosonography and electromyography mapping easily
      recognize external sphincter disruption with high concordance. Partial defects
      are better diagnosed by anal endosonography. A study of pudendal nerve terminal
      motor latency is useful in the exploration of faecal incontinence because
      pudendal neuropathy occurs frequently in association with a sphincter defect.

PMID- 7590021
TI  - [Percutaneous treatment of malignant stenoses of the hilum].
AB  - PURPOSE: The endoscopic treatment of malignant hilar obstruction is followed in
      70% of the case by infection of undrained biliary sectors. We report the
      influence of complete biliary drainage on post procedural cholangitis. METHOD:
      From January 1990 to January 1993 we treated 120 consecutive patients presenting
      with a malignant hilar obstruction. There were 61 women and 59 men, mean age 65
      +/- 7.5 years. The level of stenosis was type II in 45 patients (37%), type III
      in 18 patients (13%) and above type III in 57 patients (48%). Complete biliary
      drainage with multiple biliary access was attempted in all patients. Long term
      internal drainage was achieved by metallic autoexpansive endoprosthesis. RESULTS:
      Complete drainage was achieved in all patients with type II or type III biliary
      stenosis. Drainage was incomplete in all patients with biliary stenosis above
      type III. Early complications were observed in 35% of the patients. Persistent
      cholangitis, the most frequent complication (22%) was only observed in patients
      with above type III biliary stenosis. Mortality at 30 days was 17%. Recurrent
      biliary obstruction was observed in 22% of the patients after an average of 187
      days. Median survival was 95 days. CONCLUSION: Complete biliary drainage prevents
      persistent cholangitis in patients with type II or III biliary stenosis without
      increasing other complications related to biliary drainage.

PMID- 7590027
TI  - [Health care patterns and colorectal cancers. Study in the population of the Cote
      d'Or between 1976 and 1990].
AB  - OBJECTIVE: The goal of this study was to analyze the characteristics of
      colorectal cancer patients associated with the distribution of the incident cases
      in the health care pattern (public, private and mixed health care options) and to
      study the development of this distribution over time. METHODS: The study
      concerned 3,403 cases of colorectal cancer diagnosed in the Cote-d'Or region,
      France between 1976 and 1990. The relationship between patient characteristics
      and the type of health care pattern was analyzed using a polychotomous logistic
      regression model. RESULTS: Data analysis indicates an uneven patient distribution
      among the public (40.6%), private (47.3%) and mixed (12.1%) sectors. The
      proportion of patients received in the public sector increased with the age of
      the patient with a proportional decrease in private and mixed sectors: compared
      with patients under 65 years cared for in the public sector, the odds ratio
      characteristic of the private sector was 0.74 for the age group 65-74 and 0.44
      for those over 74 years. The odds ratios characteristic of the mixed sector were
      0.71 and 0.41 respectively. Cases demonstrating symptoms received care more often
      in the private sector (48.3%) than in the public (38.7%) or mixed (13%) sectors,
      whereas those diagnosed in patients with no digestive disorders as well as those
      diagnosed in emergency situations were mainly cared for in the public sector.
      Cancers in advanced stages were more often treated in the public sector. In the
      case of palliative treatment, the patients were more often treated in the public
      sector than in the private sector or mixed sector. This phenomenon was more
      marked in the case of symptomatic treatments: with curative treatment taken as
      the category of reference, the odds ratios associated with symptomatic treatment
      were 0.38 for the private sector and 0.18 for the mixed sector. Over the period
      of time examined, there was an increase in the proportion of patients receiving
      care in the private sector when they lived in the area serviced by Dijon or in
      areas without a health "structure". Patients residing in areas with a general
      hospital unchanged over time. Relatively disadvantaged social categories were
      more often associated with care in the public sector. CONCLUSIONS: This study
      shows that the characteristics of colorectal cancer patients differ between the
      public and private sectors. It shows the differences in recruitment of health
      care structures according to the treatment of those patients. The study provides
      information useful in conceiving regional schemes of health care organisation.

PMID- 7590028
TI  - [Simultaneous study of duodenal and biliopancreatic bicarbonates in rats].
AB  - OBJECTIVES: The aim of the present study was to assess the relative contribution
      of duodenal and biliopancreatic bicarbonate secretion to acid neutralization in
      the duodenum, in basal conditions, during stimulation by PGE2 and during acid
      infusion in the duodenum. METHODS: Forty rats were anaesthetized and the duodenum
      was infused with 0.9% saline. Bicarbonate originating from duodenal mucosa and
      from biliopancreatic secretion was independently collected and measured. In
      neutralization studies, HCl was infused in the duodenum, and the amount of
      residual acid escaping from the duodenum was determined with and without bile
      and/or pancreatic juice diversion. RESULTS: Basal duodenal and biliopancreatic
      bicarbonate outputs were respectively 10.0 +/- 0.66 and 2.4 +/- 0.31 mumol/10
      min. PGE2 increased duodenal mucosal bicarbonate by about 100%. Eighty-five
      percent of infused HCl was neutralized by duodenal mucosal bicarbonate. In
      neutralizing the remaining 15%, pancreatic secretion was slightly predominant,
      46% for a HCl concentration of 5 mM and 71% for a HCl concentration of 40 mM.
      CONCLUSIONS: These results shows that in the anaesthetized rat, available
      bicarbonate in the duodenal lumen and HCl neutralization ability are mainly
      dependent upon bicarbonate secreted by the duodenal mucosa.

PMID- 7590029
TI  - [Butyrate and hemorrhagic rectocolitis].

PMID- 7590031
TI  - ["Dysphagia lusoria". Physiopathological discussion apropos of a clinical case].
AB  - We report the observation of a patient suffering from dysphagia lusoria, a
      dysphagia caused by an anomalous form of the right subclavian artery. The
      diagnosis was confirmed by aortic arch angiography and cine-oesophagogram.
      Oesophageal manometric study revealed segmental hypoperistalsis and anti
      peristalsis. Dysphagia disappeared with cisapride. This observation suggests that
      dysphagia lusoria is caused by oesophageal motility disorders and not by vascular
      compression.

PMID- 7590030
TI  - [Hepatosplenic angiosarcoma complicated by hemoperitoneum and disseminated
      intravascular coagulation. Treatment by arterial embolization and chemotherapy].
AB  - We report a case of hepatic and splenic angiosarcoma in a 34 year-old man
      presenting with hemoperitoneum and consumption coagulopathy. Histological and
      immunohistological diagnosis was based on a biopsy specimen obtained through the
      transjugular route. Embolization via the splenic artery for the most significant
      lesions and intravenous chemotherapy resulted in a partial response in the liver
      and splenic tumour masses and survival with a good quality of life. The initial
      complications recurred after chemotherapy was stopped and death occurred after 15
      months. The benefit of arterial embolization and chemotherapy in this rare and
      usually rapidly fatal disease should be assessed in other patients.

PMID- 7590033
TI  - [Severe hepatitis, complicating heat-stroke induced by exertion, successfully
      treated by neuroleptic and anticholinergic agents].

PMID- 7590032
TI  - [Major hypoproteinemia revealing enteritis caused by Yersinia enterolytica and
      cytomegalovirus at the onset of chronic lymphocytic leukemia].
AB  - We report the first case of probable protein-losing enteropathy revealing a
      cytomegalovirus/Yersinia enterolytica infection at the onset of a chronic
      lymphocytic leukaemia. Severe hypoprotidaemia, digestive tract yersiniosis,
      ulcerative and microgranulomatous enteritis with a large number of cytomegalic
      inclusions in mucosal cells, and incipient lymphoid proliferation were the most
      characteristic findings.

PMID- 7590034
TI  - [Hypoplasia of the gallbladder associated with a dilatation of the common bile
      duct: an unusual anomaly].

PMID- 7590036
TI  - [Unusually high level of CA 19-9 in chronic pancreatitis].

PMID- 7590037
TI  - [Esophageal lesions during varicella in an immunocompromised patient].

PMID- 7590035
TI  - [Acute hepatitis induced by minocycline].

PMID- 7590038
TI  - [Endoscopic treatment of hemorrhagic Mallory-Weiss syndrome].

PMID- 7590042
TI  - [Emergence of HBe antigen-negative mutants of hepatitis B virus].

PMID- 7590041
TI  - [Post-surgical intractable gastric bezoars: usefulness of laser therapy].

PMID- 7590039
TI  - [Value of intravenous erythromycin before gastroscopy in the upper digestive
      hemorrhage].

PMID- 7590040
TI  - [Obstructive inflammatory fibroid polyp of the cardia].

PMID- 7590043
TI  - [Eradication of Helicobacter pylori and treatment of the stomach ulcer].

PMID- 7590044
TI  - Small flat cancer of the rectum: clinicopathologic and endoscopic features.
AB  - The clinicopathologic and endoscopic features of 15 patients with small flat
      cancer of the rectum were investigated. Whereas 4 patients had hematochezia, the
      remaining 11 patients were asymptomatic, and stool positive for occult blood was
      the only remarkable clinical feature in 8 of them. Endoscopic features were
      slight elevation with central depression in 8 lesions, flat-topped elevation in
      4, and shallow depression with irregular margin in 3. The surface of the tumor
      was often faint red in color and frequently characterized by mucosal friability.
      Five flat rectal cancers were missed during initial endoscopy, and they were
      found by repeated endoscopic examination. Three flat cancers were not identified
      in the distal rectum until retroflexed colonoscopic observation was performed.
      Although all tumors were smaller than 2 cm in diameter and 6 of them were under 1
      cm, 9 lesions had deeply invaded the submucosal layer and 7 tumors showed
      lymphovascular permeation. Two lesions of 1 cm or greater had metastasized to
      perirectal lymph nodes. These results suggest that careful observation during
      endoscopy is necessary to detect flat rectal cancers, and a U-turn to examine the
      anorectal junction should be routinely done in the appropriate age group.

PMID- 7590045
TI  - Flat neoplastic lesions of the colon and rectum detected by high-resolution video
      endoscopy and chromoscopy.
AB  - Because small flat colorectal neoplastic lesions (i.e., flat adenomas and flat
      adenocarcinomas) may be as translucent as the surrounding mucosa, they can remain
      undetected at conventional endoscopy. By combining high-resolution video
      endoscopy and chromoscopy, we detected 109 colorectal flat neoplastic lesions in
      55 of 232 patients studied. Forty-three (78%) of the 55 patients with flat
      neoplastic lesions were over 60 years of age. No flat neoplastic lesions were
      seen in patients under 40 years of age. Flat neoplastic lesions were more
      frequent in men (35%) than in women (15%). Seventy-seven (71%) of the 109 flat
      neoplastic lesions measured 0.5 cm or less, 23 (21%) between 0.6 and 1.0 cm, and
      9 (8%) more than 1.0 cm. Low-grade dysplasia and high-grade dysplasia were found
      in 94 (86%) and 13 (12%) of the flat neoplastic lesions, respectively.
      Adenocarcinoma was diagnosed in 3 (3%) flat lesions: 1 (1%) carcinoma originating
      in a flat adenoma and 2 (2%) adenocarcinomas without recognizable adenomatous
      elements. No adenocarcinomas were seen in lesions measuring 1.0 cm or less.
      Fourteen flat neoplastic lesions had a central depression at endoscopy. Flat
      neoplastic lesions with central depression more frequently showed high-grade
      dysplasia (43%) than did flat neoplastic lesions without central depression (7%).
      Central depression in flat neoplastic lesions should be considered a possible
      endoscopic marker for severe dysplasia. Our results suggest that flat neoplastic
      lesions occur more frequently than previously reported in Scandinavia. Flat
      adenomas may play an important role in the histogenesis of colorectal cancer.

PMID- 7590046
TI  - Intravenous antispasmodic and patient-controlled analgesia are of benefit for
      screening flexible sigmoidoscopy.
AB  - The possible benefits of premedication with the antispasmodic hyoscine n-butyl
      bromide (hyoscine) and analgesia with inhaled nitrous oxide/oxygen mixture
      (nitrous oxide) were assessed in a double-blinded, placebo-controlled trial.
      Consecutive patients at normal risk for cancer undergoing screening flexible
      sigmoidoscopy were randomly allocated to receive either (1) intravenous hyoscine
      20 mg plus inhaled oxygen on demand (n = 40), (2) sterile water injection plus
      inhaled nitrous oxide on demand (n = 48), or (3) sterile water injection plus
      inhaled oxygen on demand (n = 43). One recently trained primary care physician
      performed all procedures. Duration of the procedure, endoscopic findings, and
      depth of insertion were recorded. After the examination, screenees rated their
      degree of pain during the procedure using a visual analogue scale. Depth of
      insertion did not differ between the three study groups, but the duration of the
      procedure was significantly less in the hyoscine group (median, 12.5 minutes) as
      compared with placebo (median, 18 minutes; p = .0008). Fifty-four percent of
      screenees chose to use the on-demand gas. Pain scores were significantly lower in
      those individuals who inhaled nitrous oxide as compared with placebo (p = .045).
      Premedication with antispasmodic shortens total procedure time for flexible
      sigmoidoscopy by a moderately experienced endoscopist as compared with placebo.
      In this study, a significant number of screenees experienced discomfort during
      flexible sigmoidoscopy, which appeared to be reduced by offering nitrous oxide
      inhalation.

PMID- 7590047
TI  - Prevention of recurrent bleeding from gastric ulcer with a nonbleeding visible
      vessel by endoscopic injection of absolute ethanol: a prospective, controlled
      trial.
AB  - We performed a prospective, randomized trial to assess the efficacy of endoscopic
      injection therapy with absolute ethanol in preventing recurrent bleeding in
      patients with nonbleeding visible vessels in gastric ulcers. During the period of
      1990 to 1993, 62 patients who bled were found to have gastric ulcers with
      nonbleeding visible vessels; all of them were enrolled for this trial. The 62
      patients were randomly divided into two groups, which were comparable at entry.
      In group I (33 patients), we performed endoscopic injection therapy with absolute
      ethanol. In group II (29 patients), we sprayed the ulcers with 0.1% epinephrine
      and thrombin. Endoscopic injection therapy with ethanol was performed at the
      second endoscopy in the patients in both groups who had recurrent bleeding. Among
      the 33 patients in group I, 4 patients (12.1%) rebled after the initial ethanol
      injection therapy, whereas 10 of 29 patients (34.5%) rebled in the control group
      (p < .05). No patients in group I required surgical intervention, and ultimate
      hemostasis was achieved in all 33 group I patients (100%), indicating that
      endoscopic ethanol injection therapy achieves ultimate hemostasis and prevents
      recurrent bleeding in patients with gastric ulcers and nonbleeding visible
      vessels.

PMID- 7590050
TI  - Endosonography of gastroesophageal varices: evaluation and follow-up of 76 cases.
AB  - Endosonography was performed in 76 patients who had endoscopically detected
      gastroesophageal varices or questionable submucosal lesions, or who were being
      evaluated for pancreatic carcinoma or pancreatitis. The result were compared with
      surgery or autopsy results. The patients were divided retrospectively into four
      groups. Group 1 consisted of 6 patients who underwent surgery or autopsy. Five
      esophageal varices and 1 fundic varix were diagnosed with endosonography and
      confirmed histologically. Group 2 consisted of 29 patients undergoing
      sclerotherapy. Intramural thickening of the esophagus and extramural collaterals
      were found in 20 of 22 patients, respectively. Endoscopy revealed fibrosis in 10
      patients. Group 3 consisted of 16 patients evaluated for pancreatic disease.
      Fifteen fundic varices, 6 cardiac varices, and 5 extramural collateral veins were
      found by EUS. Group 4 consisted of 16 patients with questionable submucosal
      lesions and 9 patients with lesions recognized endoscopically as varices. EUS
      found varices in all 25 patients. In conclusion, EUS is an important procedure in
      the diagnosis and follow-up of gastroesophageal varices, and in the
      identification of questionable abnormalities found endoscopically. The effect of
      sclerotherapy can be demonstrated as mural thickening with disappearance of
      submucosal varices.

PMID- 7590049
TI  - Changes in portal hypertensive gastropathy after endoscopic variceal
      sclerotherapy or ligation: an endoscopic observation.
AB  - To determine the effect of endoscopic variceal sclerotherapy or ligation on
      portal hypertensive gastropathy, 90 cirrhotic patients with esophageal variceal
      bleeding were randomized to receive sclerotherapy (n = 44) or ligation (n = 46).
      Follow-up endoscopic observations of the gastric mucosa were recorded at 3-month
      intervals after variceal eradication. Clinical characteristics in both groups
      were similar. Probability for a change in the severity of portal hypertensive
      gastropathy was not related to method of eradication. Most cases of portal
      hypertensive gastropathy that changed in severity returned to baseline status
      with time, but the return was faster after ligation than after sclerotherapy.
      According to the results of multivariate analyses, sclerosant volume was the only
      factor associated with a significant difference between the group with static
      gastropathy (n = 15) and that with dynamic change in gastropathy (n = 23) after
      sclerotherapy. No relevant factors were found in the patients receiving ligation.
      We conclude that changes in the severity of portal hypertensive gastropathy after
      endoscopic variceal sclerotherapy or ligation are reversible. Most cases of
      gastropathy return to baseline status sooner or later.

PMID- 7590048
TI  - Flexible sigmoidoscopy plus air-contrast barium enema versus colonoscopy for
      evaluation of symptomatic patients without evidence of bleeding.
AB  - One hundred forty-nine patients aged 40 years or more with symptoms suggestive of
      colonic disease but without evidence of gastrointestinal bleeding (absence of
      hematochezia, normal serum levels of hemoglobin, and at least one test negative
      for fecal occult blood) were randomized to undergo either initial colonoscopy or
      initial flexible sigmoidoscopy plus air-contrast barium enema. Patients with
      incomplete initial colonoscopy and certain patients with polyps seen on flexible
      sigmoidoscopy plus barium enema underwent the alternative procedure (barium enema
      or colonoscopy). The main results were as follows: First, the overall prevalence
      of cancer in the study was very low (0.67%). Second, initial flexible
      sigmoidoscopy plus barium enema detected more patients with diverticulosis than
      did initial colonoscopy (46% versus 31%; p = .01). Initial colonoscopy detected
      more persons with adenomas (p = .06) than did initial flexible sigmoidoscopy plus
      barium enema. Patients undergoing initial flexible sigmoidoscopy plus barium
      enema require the alternative procedure (24%) than were patients undergoing
      initial colonoscopy (6%; p = .002). Third, sensitivity analyses suggested that
      for most areas in the United States, initial colonoscopy would be more cost
      effective for the outcomes of detection of adenomas and detection of large
      adenomas, although very few patients in the study had large adenomas. We conclude
      that the prevalence of colorectal cancer in persons with colonic symptoms but no
      evidence of bleeding is low and is comparable with the prevalence in an
      asymptomatic population. Cost-effective selection of imaging strategies in this
      population can be based on demographic factors such as age and sex, which are
      better predictors of the presence of adenomas than are symptoms.

PMID- 7590052
TI  - Intravenous sedation in pediatric upper gastrointestinal endoscopy.
AB  - To assess the safety and efficacy of intravenous sedation in pediatric upper
      endoscopy, all elective outpatient procedures performed during a 2-year period
      (January 1, 1991 through December 31, 1992) were retrospectively reviewed. Of 614
      children, 553 received intravenous meperidine and midazolam; 61 received fentanyl
      and midazolam. The mean dose of meperidine was 1.5 +/- 0.7 mg/kg and of fentanyl
      0.0031 +/- 0.0014 mg/kg. Less midazolam was needed for children receiving
      fentanyl than for those receiving meperidine (0.05 +/- 0.03 mg/kg versus 0.08 +/-
      0.05 mg/kg, p < 002). Recovery time (minutes) was shorter for those receiving
      fentanyl (74.7 +/- 22.8 versus 95.1 +/- 23.0, p < .003). Side effects occurred in
      117 patients (19.1%), of which the majority were mild (83%); all were transient
      with no residual sequelae. Inability to complete the procedure occurred in fewer
      than 1%. We conclude that both combinations of medication are safe and effective
      for children of all ages. The use of fentanyl/midazolam results in a shorter
      recovery time and a lower dose of midazolam.

PMID- 7590051
TI  - Femoral vein stasis during laparoscopic cholecystectomy: effects of graded
      elastic compression leg bandages in preventing thrombus formation.
AB  - Venous stasis of the legs during laparoscopic cholecystectomy was compared
      between patients without graded compression leg bandages (Group 1; n = 12) and
      patients with such bandages (Group 2; n = 12) by measuring mean blood flow
      velocity and cross-sectional area of the femoral vein using a color Doppler
      ultrasonography. In Group 1, when velocity and area were measured in the supine
      position, a significant decrease in velocity (p < .05) and a significant increase
      in area (p < .05) occurred after abdominal insufflation to 10 mm Hg. These
      changes were greater during abdominal insufflation in the reverse Trendelenburg
      position than during abdominal insufflation in the supine position. In Group 2,
      flow velocity was significantly higher (p < .05) before abdominal insufflation as
      compared with Group 1. After abdominal insufflation to 10 mm Hg and a postural
      change, velocity significantly decreased (p < .05) and area significantly
      increased (p < .05) in Group 2, similar to the results in Group 1. During
      abdominal insufflation at 5 mm Hg or lower, the use of the graded compression
      bandage was found to be useful for preventing femoral vein stasis. During
      abdominal insufflation at 10 mm Hg or in the reverse Trendelenburg position, the
      bandage did not prevent femoral vein stasis.

PMID- 7590054
TI  - A novel technique for percutaneous endoscopic gastrojejunostomy tube placement.

PMID- 7590053
TI  - An improved approach to delivery of enteral nutrition in the intensive care unit.

PMID- 7590055
TI  - A serial transparent endoscopic elastic band ligator.

PMID- 7590056
TI  - Strongyloidiasis: new endoscopic findings.

PMID- 7590057
TI  - Absent minor papilla and an unusual drainage system in a patient with pancreas
      divisum.

PMID- 7590059
TI  - Choledocholithiasis associated with portal biliopathy in patients with
      extrahepatic portal vein obstruction: management with endoscopic sphincterotomy.

PMID- 7590058
TI  - Extrahepatic biliary obstruction resulting from a pancreatic pseudoaneurysm.

PMID- 7590060
TI  - Flat adenomas and cancers.

PMID- 7590062
TI  - Laparoscopically assisted panenteroscopy.

PMID- 7590061
TI  - Small flat adenomas appear to have little clinical importance in Western
      countries.

PMID- 7590063
TI  - Gastric outlet obstruction and upper gastrointestinal bleed: a PEG complication.

PMID- 7590064
TI  - Anatomy of the thoracic duct: an endosonographic study.

PMID- 7590065
TI  - Early acute gastric dilatation following percutaneous endoscopic gastrostomy.

PMID- 7590066
TI  - Respiratory function after injection sclerotherapy of oesophageal varices.

PMID- 7590069
TI  - [Current status of the plasmapheresis problem].

PMID- 7590068
TI  - [First results of bone marrow transplantation in acute and chronic leukemia at
      the Byelarus Center for Bone Marrow Transplantation].
AB  - The first 10 bone marrow transplantations (BMT), 6 of the allogenic (allo-BMT)
      and 4 autologous (auto-BMT) were performed from February to June 1994 in Byelarus
      Center for Bone Marrow Transplantation. Two of the patients were experiencing the
      first complete remission of acute lymphoblastic leukemia (ALL), one of them - the
      first ALL recurrence, three patients with acute myeloblastic leukemia had the
      first complete remission, four patients had a chronic phase of chronic myeloid
      leukemia. In auto-BMT bone marrow (BM) was stored in liquid hydrogen after
      programmed freezer. An average yield of nucleated cells (NC) after taking and
      separation of allo-BM made up 3.0 x 10(8) cell/kg and 2.7 x 10(8) cell/kg in auto
      BMT. After thawing of BM NC yield reached 1.5 x 10(8) cell/kg (0.8-2.3) x 10(8)
      cell/kg. CFU concentrations persisted at 24.7 x 10(4) (5.0-40.4) x 10(4) cell/kg
      body weight. The mean duration of leukocyte, neutrophil and platelet rise to the
      levels of over 1.0 x 10(9)/l, 0.5 x 10(9)/l, 20 x 10(9) cell/l, respectively, and
      the last time red cells were transfused were 23 (19-33), 23 (19-31), 22 (9-51),
      4.5 (0-19), respectively. One ALL (first complete remission) patient died on day
      52 after allo BMT of severe hepatic venous-occlusive disease. The other ALL
      patient (the first relapse) developed another relapse on day 112 after BMT. The
      rest 8 patients are in satisfactory condition.

PMID- 7590067
TI  - [Clinical experience using the cryoprotector "hecmolit" in performing autologous
      bone marrow transplantation].
AB  - The authors summarize clinical evidence obtained on the efficacy of a new Russian
      cryoprotector hecmolit in the conduction of autotransplantation of 8 patients
      with acute leukemia. The markers of the preserved hemopoietic potential of the
      unfrozen bone marrow were the amount of myelokaryocytes, their viability in the
      test with vital stain, CFU-GM level. Infusions of the marrow suspension
      incorporating hecmolit (120-180 ml) produced minimaL side effects. After thawing
      myelokaryocytes remained in the amount 81.7 +/- 8.2% or 1.6 +/- 0.4 x 10(8) cell
      / kg, on the average. Estimation of the aggregates in terms of the weight
      revealed that hemopoietic potential was sufficient for the transplant survival
      (2.9 +/- 0.7 x 10(3) CFU-GM/kg) though only 50 +/- 10% of CFU-GM remained safe.
      Hecmolit tolerance was satisfactory. The preparation is thought convenient for
      bone marrow transplantation practice.

PMID- 7590073
TI  - The pharmacology of immunosuppressant drugs in skin transplant rejection in mice
      and other rodents.
AB  - 1. Skin transplantation in rodents is a convenient, widely used method,
      particularly in mice. It is used as much as an indicator of immune responsiveness
      as for pharmacological studies. 2. Many differences exist in experimental
      protocols, both for transplantation and drug administration and in this review,
      the increase in graft survival time with respect to control times is used to
      indicate drug effects, in an attempt to account for these differences. 3. The
      mechanisms underlying skin graft rejection in rodents are described, emphasising
      the crucial role of both helper and effector T cells. 4. The pharmacology of
      clinically-used immunosuppressants, including CsA, FK506, rapamycin and purine or
      pyrimidine synthesis inhibitors, in rodent models of skin transplantation is
      reviewed. 5. The effects of other potential immunosuppressants and compounds
      modulating immune responses are described, including the effects of UV light and
      involvement of platelet-derived factors, prostaglandins and thromboxanes.

PMID- 7590072
TI  - Reflex parasympathetic vasodilatation in facial skin.
AB  - 1. The present report summarizes data from recent studies dealing with
      parasympathetic innervation of blood vessels in the lower lips (gingiva) of cats.
      2. A study using the HRP tracing technique shows that blood vessels in the lower
      lip are innervated by postganglionic fibres originating in the otic ganglion, but
      not in the pterygopalatine ganglion. 3. There is a dual innervation of the cat
      lower lip by two groups of parasympathetic vasodilator fibres; in one case,
      fibres originating from the facial nerve root are distributed to the lower lip
      via chorda tympani nerve and in the other, fibres emanating from the
      glossopharyngeal nerve root project to the lower lip via the otic ganglion. 4.
      Parasympathetic reflex vasodilatation can be elicited by activation of the
      trigeminal (somatic), vagus (visceral), chorda tympani (gustatory) and nasal
      (chemical and mechanical) stimulation in the lower lips of cat. 5.
      Parasympathetic reflex vasodilatation elicited by somatic stimulation is mediated
      via the otic ganglion but not via the pterygopalatine ganglion, indicating that
      parasympathetic neurons, particularly those running as efferents in the
      glossopharyngeal nerve, are involved in the vasodilatation elicited by somatic,
      visceral and nasal stimulation.

PMID- 7590071
TI  - P2 purinergic receptors for diadenosine polyphosphates in the nervous system.
AB  - 1. The actions of diadenosine polyphosphates, diadenosine tetraphosphate (Ap4A),
      diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) in the
      nervous system have been reviewed. 2. In the peripheral nervous system,
      diadenosine polyphosphates bind to P2-purinergic receptors such as the P2Y in
      chromaffin cells and Torpedo synaptosomes, P2X in vas deferens and urinary
      bladder and also Torpedo synaptosomes and P2U in endothelial chromaffin cells. 3.
      In the central nervous system ApnA compounds can act through P2X-purinoceptors
      opening cation channels in nodose ganglion neurones. Diadenosine polyphosphates
      bind to a P2d-purinergic receptor in rat brain synaptic terminals and
      hippocampus, linked to protein kinase C (PKC) activation. 4. P4-purinoceptors are
      specific receptors for diadenosine polyphosphates, coupled to the Ca2+ influx, in
      the central synapses. This purinoceptor is not activated by ATP and synthetic
      analogs. The P4-purinoceptor could act as a positive modulator of the synaptic
      transmission, giving even more importance to diadenosine polyphosphates as
      neurotransmitters.

PMID- 7590074
TI  - Actions of a small cardioactive peptide from Mytilus, APNFLAYPRLamide, on central
      neurones of Helix aspersa.
AB  - 1. Mytilus small cardioactive peptide (SCP) was originally isolated from the
      anterior byssus retractor muscle of Mytilus edulis, with a primary structure,
      APNFLAYPRLamide. The mechanisms of action of this peptide were examined on
      identified central neurones of the snail, Helix aspersa, using intracellular
      recordings and a two electrode voltage clamp. 2. 50 microM APNFLAYPRLamide could
      elicit a long term excitation on F2 neurones, in normal saline, Na(+)-free
      saline, Ca(2+)-free saline or in 10 mM Co2+ saline. This indicates that the
      excitatory effect of APNFLAYPRLamide involved an increase in membrane conductance
      to both Na+ and Ca2+. 3. 10 microM APNFLAYPRLamide potentiated the Ca2+ inward
      current of F2 neurones while reversibly reducing the ACh-induced membrane current
      of these neurones. Forskolin had identical effects to those of APNFLAYPRLamide.
      This indicates that the action of APNFLAYPRLamide may be through a second
      messenger. In contrast APNFLAYPRLamide potentiated a cholinergic EPSP evoked in
      F2 neurones. 4. YPRLamide was inactive even at higher concentrations, for
      example, 100 microM, while LAYPRLamide exhibited activity but with a lower
      potency. This indicates that LAYPRLamide is the minimum structure required for
      activating this class of SCP-like peptide receptor. However, the mode of action
      of APNFLAYPRLamide on the Na+ current of F2 neurones requires further
      investigation.

PMID- 7590070
TI  - [Proceedings of the International Symposium Current Problems of Childhood
      Panmyelopathies: Focus on Myelodysplastic Syndrome. Moscow, September 8-12,
      1994].

PMID- 7590077
TI  - Effect of Teucrium stocksianum on paracetamol-induced hepatotoxicity in mice.
AB  - 1. Hepatoprotective activity of an ethanolic extract of Teucrium stocksianum was
      investigated against paracetamol-induced hepatic damage in mice. 2. Paracetamol
      at an oral dose of 0.6 g/kg produced about 94% mortality in mice while
      pretreatment with the plant extract (0.5 and 1 g/kg for 5 days) reduced the death
      rate to 0%. 3. Paracetamol (0.6 g/kg, orally) produced liver damage as manifested
      by significant rises in liver weight, plasma aspartate aminotransferase (AST)
      activity and bilirubin concentration, pentobarbitone-induced sleeping time, and
      by the significant depletion of reduced glutathione (GSH) in the liver. 4.
      Pretreatment of mice with T. stocksianum at the above doses significantly
      ameliorated all the paracetamol-induced signs of liver damage described above. 5.
      T. stocksianum did not produce any lethality or adverse effects in the livers of
      treated mice. 6. These results indicate that T. stocksianum ethanolic extract
      contains hepatoprotective constituents, and suggest further work on the isolation
      and characterization of these constituents which may potentially be used as
      hepatoprotective agents.

PMID- 7590076
TI  - The effect of physostigmine on acid-base status in arterial and venous blood of
      anaesthetized rabbits following hypovolemic shock.
AB  - 1. The effects of physostigmine (70 micrograms kg-1, intravenously) on acid-base
      status in arterial and venous blood were studied in anaesthetized rabbits
      subjected to hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced using
      intermittent bleeding of 50% of the estimated blood volume, during 30 min.
      Experimental group was treated with physostigmine (70 micrograms kg-1 body mass,
      intravenously) and the control group with the same volume (0.1 ml) of saline,
      immediately after bleeding. Blood samples were taken before and after bleeding
      (0, 15 and 60 min). 3. It was found that physostigmine increased the mean
      arterial blood pressure, did not change the heart rate, and improved survival of
      the animals. 4. These effects of physostigmine were associated with significant
      decrease in venous pH, produced mainly by increased PCO2. This can partly be
      explained in terms of additional vasoconstriction due to physostigmine action. 5.
      In arterial blood decreased pH, decreased standard bicarbonate, negative values
      of excess base and decreased PCO2 were observed both in physostigmine-treated and
      the control group of animals, indicating partly respiratory compensated metabolic
      acidosis. These findings indicate that the hypertensive effect of physostigmine
      in shock was not accompanied by more severe disturbance in arterial acid-base
      status than was observed in hypovolemic shock alone.

PMID- 7590078
TI  - Peculiar effects of isradipine and darodipine on the rat brain dopaminergic
      system.
AB  - 1. Darodipine and isradipine are dihydropyridine calcium antagonists which easily
      cross the blood-brain barrier displaying high affinity and specificity for the
      brain "L" type voltage-sensitive calcium channel. In rat striatum and fronto
      parietal cortex the effects of i.p. administration of these drugs on the
      dopaminergic system were evaluated. 2. Both drugs showed neuroleptic-like
      activity on spontaneous motility at a dose of 5 mg/kg or more. 3. Isradipine,
      being almost ineffective in the frontoparietal cortex, affected the striatal DA
      turnover. On the contrary, darodipine affected the DA turnover of the
      frontoparietal cortex, being almost ineffective in the striatum. 4. Both drugs,
      unlike nimodipine, appeared to display their antidopaminergic effects by
      enhancing the intraneuronal DA metabolism. 5. It was concluded that the
      antidopaminergic properties of isradipine and darodipine are characterized by
      their regional specificity and a peculiar profile of actions. However, these
      drugs (as well as nimodipine and other calcium antagonists) show neuroleptic-like
      effects at doses which should markedly affect the cardiovascular system.

PMID- 7590079
TI  - Preventive and curative effects of Artemisia absinthium on acetaminophen and CCl4
      induced hepatotoxicity.
AB  - 1. Effect of aqueous-methanolic extract of Artemisia absinthium (Compositae) was
      investigated against acetaminophen- and CCl4-induced hepatic damage. 2.
      Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice while
      pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to
      20%. 3. Pretreatment of rats with plant extract (500 mg/kg, orally twice daily
      for two days) prevented (P < 0.01) the acetaminophen (640 mg/kg) as well as CCl4
      (1.5 ml/kg)-induced rise in serum transaminases (GOT and GPT). 4. Post-treatment
      with three successive doses of extract (500 mg/kg, 6 hr) restricted the hepatic
      damage induced by acetaminophen (P < 0.01) but CCl4-induced hepatotoxicity was
      not altered (P > 0.05). 5. Plant extract (500 mg/kg) caused significant
      prolongation (P < 0.05) in pentobarbital (75 mg/kg)-induced sleep as well as
      increased strychnine-induced lethality in mice suggestive of inhibitory effect on
      microsomal drug metabolizing enzymes (MDME). 6. These results indicate that the
      crude extract of Artemisia absinthium exhibits hepatoprotective action partly
      through MDME inhibitory action and validates the traditional use of plant in
      hepatic damage.

PMID- 7590080
TI  - LiCl uncouples signal transduction in morphine-induced supraspinal
      antinociception in mice.
AB  - 1. The present study examined whether LiCl antagonism of morphine-induced
      antinociception in mice occurs at mu-opioid receptors. 2. The antinociceptive
      ED50 value of intracerebroventricular morphine was maximally increased compared
      to controls 18 hr after LiCl (10 mmol/kg, s.c.) and remained significantly less
      (P < 0.05) 7 and 14 days after once-daily LiCl treatment. 3. There was no
      significant difference in [3H]-[D-Ala2,N-MePhe4,Gly- ol5]enkephalin affinity or
      receptor density compared to controls (KD = 0.43 nM, Bmax = 54.8 +/- 9.3 pM). 4.
      These results suggest that LiCl's effect is not on mu-opioid receptors, but
      rather on some distal site.

PMID- 7590081
TI  - Effects of vinca alkaloids on rat parotid and submandibular glands function in
      vivo.
AB  - 1. Vincristine (1 mg/kg) and vinblastine (2 mg/kg) were injected
      intraperitoneally into the rats, 24 hr before the experiments. 2. Animals were
      anesthetized with 50 mg/kg of sodium pentobarbital and saliva was collected from
      vincristine-treated, vinblastine-treated and control animals using 8 mg/kg of
      pilocarpine as secretagogue. 3. Parotid saliva was analyzed for protein, amylase
      and Ca2+ content, and submandibular saliva for flow rate, protein and Ca2+
      concentration. 4. Saliva from two treated groups was significantly lower (P <
      0.01) in flow rate, amylase and protein content than that of control group.
      Calcium level was significantly increased (P < 0.05) in treated animals. 5. It is
      concluded that the antisecretory effects of vinca alkaloids may be consistent
      with their actions on salivary cell microtubules.

PMID- 7590075
TI  - Effects of amiodarone on beating rate and Na-K-ATPase activity in cultured
      neonatal rat heart myocytes.
AB  - 1. The purpose of this study was to examine the possibility that the cellular
      action of amiodarone is mediated by inhibition of thyroid hormone regulatory
      functions within the myocardial cell. We measured the rate of cell beating and
      the activity of Na-K-ATPase in cultured neonatal rat heart myocytes. 2.
      Amiodarone (0.25 and 1 microgram/ml) reduced beating rate up to 75% within 20
      min, and Na-K-ATPase activity up to 40% within 2 hr. No toxic effects were
      detected in the treated cells. 3. The inhibitory actions of amiodarone on beating
      rate and Na-K-ATPase activity were the same in myocytes grown in the presence or
      absence of 3-iodothyronine (T3, 5 nM). 4. These data indicate that amiodarone
      affects beating rate and Na-K-ATPase activity independently of thyroid hormone.
      It is suggested that interference of amiodarone with thyroid hormone action is
      not the only mechanism by which this drug modulates some functions of the
      myocardial cell.

PMID- 7590082
TI  - Characterization of ruthenium red as an inhibitor of neurogenic inflammation in
      the rat trachea.
AB  - 1. We investigated the ability of ruthenium red, an inorganic dye with capsaicin
      antagonist properties, to inhibit capsaicin-induced plasma extravasation in the
      rat trachea. 2. The amount of plasma extravasation produced by intravenous
      capsaicin was reduced dose-dependently by i.v. ruthenium red. Complete inhibition
      was achieved with a dose of 5 mumol/kg. 3. The inhibitory effect of ruthenium red
      persisted for at least 16 hr after its administration, but was not present 24 hr
      later. 4. Ruthenium red did not reduce the amount of plasma extravasation
      produced by electrical stimulation of the vagus nerve, nor the amount produced by
      intravenous substance P or platelet-activating factor. 5. Prior exposure to a
      high dose of capsaicin reduced the amount of plasma extravasation produced by a
      second capsaicin exposure 48 hr later. However, giving ruthenium red 30 min
      before the initial capsaicin exposure largely prevented this loss of sensory
      nerve function. 6. We conclude that systemic administration of ruthenium red
      produces long-lasting, selective, and reversible inhibition of capsaicin-induced
      plasma extravasation in the rat trachea. Moreover, ruthenium red attenuates the
      long-term, desensitizing effect of capsaicin on sensory nerves.

PMID- 7590083
TI  - Effects of efonidipine hydrochloride (NZ-105), a calcium antagonist, on renal
      function in conscious spontaneously hypertensive rats.
AB  - 1. We investigated the effects of short- and long-term administration of
      efonidipine hydrochloride (NZ-105), 1,4-dihydropyridine derivative, in conscious
      spontaneously hypertensive rats (SHR). 2. Oral administration of NZ-105 for 12
      weeks caused diuretic and natriuretic effects, which were not attenuated during
      the experimental period. 3. In the short-term experiment for investigating the
      mechanism of the diuretic effect, intravenous injection of NZ-105 (0.03 mg/kg of
      body weight) significantly increased the urine volume (UV), renal plasma flow
      (RPF) and glomerular filtration rate (GFR). The increment rate of UV and RPF was
      105.4 +/- 17.8% and 111.7 +/- 72.8%, respectively, which were larger than the
      increment rate of GFR (38.5 +/- 14.0%). 4. The diuretic or natriuretic effect of
      NZ-105 was suggested to be due to both the inhibition of sodium reabsorption and,
      at least in part, the increase of GFR.

PMID- 7590084
TI  - Cardiovascular selectivity of 1,4-dihydropyridine derivatives, efonidipine (NZ
      105), nicardipine and structure related compounds in isolated guinea-pig tissues.
AB  - 1. The cardiovascular selectivities of 1,4-dihydropyridine derivatives,
      efonidipine (NZ-105), nicardipine, 3NZ5NIC (the drug with NZ-105-type side-chain
      at C3 position and nicardipine-type at C5) and 3NIC5NZ (the drug with nicardipine
      type side chain at C3 and NZ-105-type at C5) were studied in vitro. 2. All four
      compounds caused relaxation of guinea-pig aortae precontracted with a high K+.
      The pEC50 values were 7.5, 8.3, 8.1 and 5.6, for NZ-105, nicardipine, 3NIC5NZ and
      3NZ5NIC, respectively. The relaxation produced by NZ-105 was slower in onset than
      those produced by the other compounds. The rate constant K(hr-1) of the
      relaxations were 0.59, 1.31, 1.02 and 1.24, for NZ-105, nicardipine, 3NIC5NZ and
      3NZ5NIC, respectively. 3. In the electrically paced guinea-pig papillary muscles,
      NZ-105, 3NIC5NZ and 3NZ5NIC, even at concentrations as high as 10(-6) M, slightly
      decreased the contractile force (by 44.9 +/- 7.1%, 58.6 +/- 5.4% and 52.2 +/-
      3.9%, respectively), whereas 10(-6) M nicardipine decreased the force by 84.9 +/-
      3.3%. The negative inotropic effect of NZ-105 and 3NIC5NZ, but not that of
      3NZ5NIC or nicardipine, was over 10 times weaker than their vasorelaxant effect.
      4. In the guinea-pig right atria, NZ-105 and nicardipine at 10(-8) M decreased
      the spontaneous contraction rate by 67.9 +/- 15.0% and 39.7 +/- 15.4%,
      respectively. 3NIC5NZ at 3 x 10(-9) M and 3NZ5NIC at 3 x 10(-8) M had little
      effect on the rate, whereas 10(-8) M 3NIC5NZ and 10(-7) M 3NZ5NIC arrested the
      beating within 3 hr after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7590085
TI  - Renal aging change of alpha 1-adrenoceptor in Wistar rats.
AB  - 1. The aging changes of density of the alpha 1-adrenoceptors in the kidney were
      evaluated with Wistar rats of several ages (8, 52 and 104 weeks old). 2.
      [3H]prazosin and [3H]YM617 (newly synthesized alpha 1-blocker) were used for the
      ligand. The Bmax of [3H]prazosin was 74.0 +/- 9.5 fmol/mg/protein in 8 week, 52.1
      +/- 7.3 fmol/mg protein in 52 week, and 31.3 +/- 4.2 fmol/mg protein in 104 week
      rats, and that of [3H]YM617 was 45.0 +/- 6.6 fmol/mg/protein in 8 week, 32.4 +/-
      5.7 fmol/mg/protein in 52 week, and 19.3 +/- 5.5 fmol/mg/protein in 104 week
      rats. 3. The Bmax of both ligands for 104 week rats was significantly decreased
      compared to 8 week rats, however, 52 week rats showed no decrease of Bmax for
      both ligands. 4. The Kd values showed no difference in these three age groups for
      both ligands. 5. Autoradiographic study supported the result above mentioned.
      Furthermore, the binding sites of alpha 1-adrenoceptors were mainly in the cortex
      (vascular wall and peritubular area) and that alpha 1-adrenoceptors were chiefly
      chlorethylclonidine dihydrochloride (CEC) insensitive.

PMID- 7590086
TI  - A similarity and a difference between two models of late eosinophil accumulation
      into the airway induced by antigen exposure in actively sensitized brown Norway
      (BN) rats.
AB  - 1. Exposure of sensitized Brown Norway (BN) rats to ovalbumin aerosol induced a
      remarkable and a sustained accumulation of eosinophils into broncho-alveolar
      lavage (BAL) fluid. 2. When male BN rats, sensitized by i.m. injection of
      ovalbumin and i.p. injection of killed Bordetella pertussis, were exposed to the
      antigen on day 14, eosinophils accumulated into BAL fluid, maximal 48 hr after
      antigen exposure. This accumulation of eosinophils was inhibited completely by
      administration of cyclosporin A (Cs A, 50 mg/kg/day) during induction phase,
      whereas it was inhibited slightly by administration of CsA (50 mg/kg) during the
      effector phase. 3. When BN rats were sensitized by weekly exposure of ovalbumin,
      eosinophils accumulated into BAL fluid, maximal 48 hr after the third exposure of
      antigen. The accumulation of eosinophils by this method was observed only in
      female rats and was inhibited completely by administration of CsA (50 mg/kg)
      during induction phase, whereas it was inhibited slightly by administration of
      CsA (50 mg/kg) during effector phase. 4. The present study demonstrates
      similarities and differences between two models of eosinophilia and also suggests
      increased function of T cells in BN rats.

PMID- 7590087
TI  - Alpha 1A-adrenoceptor subtype effectively increases Ca(2+)-sensitivity for
      contraction in rabbit thoracic aorta.
AB  - 1. Norepinephrine and phenylephrine increase cytosolic Ca2+ concentration
      ([Ca2+]i) and muscle tension, which shows positive correlation between [Ca2+]i
      and tension development. 2. The slopes of regression lines between [Ca2+]i and
      tension development for norepinephrine and phenylephrine in tissues treated with
      an irreversible alpha 1B-adrenoceptor selective blocking agent, 10(-4) M
      chloroethylclonidine, were significantly steeper than those with untreated
      tissues. 3. Myosin light chain kinase inhibitors, KT5926 (3 x 10(-6) M) and K252a
      (10(-6) M) more selectively reduced the contraction produced by norepinephrine (3
      x 10(-7) M) than that produced by clonidine (3 x 10(-6) M). 4. In the
      chloroethylclonidine-treated tissues, KT5926 and K252a did not tend to affect the
      contraction induced by norepinephrine and clonidine. 5. These results suggest
      that the contractile response through the alpha 1A-adrenoceptor subtype causes a
      greater muscle tension than that through the alpha 1B-subtype at the same level
      of [Ca2+]i, and that the alpha 1A-adrenoceptor subtype mainly activates myosin
      light chain kinase independent pathways of contractile mechanisms in vascular
      smooth muscle of rabbit.

PMID- 7590088
TI  - Isolation of brefeldin A.
AB  - 1. A chromatographic method for the isolation of brefeldin A (BFA) from the
      culture medium of Penicillium brefeldianis has been developed. BFA is adsorbed on
      a reversed-phase (C18) silica, desorbed by methanol, and the crystalline BFA
      precipitated from the concentrated aqueous solution. The yield of crystalline BFA
      is 121 mg/l of culture medium from a sample containing 204 mg/l determined by
      analytical HPLC. 2. The detection limit of BFA is 50 ng by analytical HPLC and
      BFA in the mother liquor of crystallization is recovered by preparative HPLC.

PMID- 7590090
TI  - Modulation of L-type Ca2+ current by isoprenaline, carbachol and phorbol ester in
      cultured rat aortic vascular smooth muscle (A7r5) cells.
AB  - 1. Effects of isoprenaline (ISO), carbachol and phorbol ester (a stimulator of
      protein kinase C) on L-type Ca2+ channels in single cultured rat aortic vascular
      smooth muscle (A7r5) cells were examined using whole-cell voltage clamp (at room
      temperature 22 degrees C). 2. With 20 mmol/l Ca2+ in the bath solution and 10
      mmol/l EGTA in the pipette solution, a slow ICa (L-type) current was observed in
      the A7r5 cell line, which was blocked by nifedipine (2 mumol/l). 3. ISO (5
      mumol/l) inhibited ICa by 18.3 +/- 2.2% (P < 0.001), and carbachol (1 mumol/l)
      also decreased ICa by 15.0 +/- 3.2% (P < 0.01). 8-Br-cAMP (1 mmol/l) and 8-Br
      cGMP (1 mmol/l) both inhibited ICa by 30.1 +/- 2.8% (P < 0.001) and 18.8 +/- 3.8%
      (P < 0.01), respectively. 4. Phorbol ester, 4-beta-phorbol-12, 13-dibutyrate
      (PDB), at 0.1-1 mumol/l, had almost no effect on ICa in most cells, but slightly
      potentiated (or slightly enhanced) the inhibitory effects of ISO. 5. Time decay
      (inactivation) of ICa consisted of two exponentials. Both the fast and slow time
      constants were slightly prolonged by ISO (5 mumol/l), and by carbachol (1
      mumol/l); PDB (1 mumol/l) slightly shortened the fast time constant only. The
      half-maximum voltages of inactivation were not significantly affected by any of
      the agents. 6. These results suggest that the L-type ICa current is modulated by
      cyclic nucleotides (cAMP and cGMP) and by PK-C stimulation, and thereby
      contribute to regulation of contraction of the vascular smooth muscle cells.

PMID- 7590091
TI  - Manganese ions penetrate via L-type Ca2+ channels and induce contraction in high
      K+ medium in ileal longitudinal muscle of guinea-pig.
AB  - 1. Mn2+ (5 mM) completely inhibited the K+ (10-60 mM)-induced ileal tonic tension
      to the baseline, however, the tension and Mn2+ uptake increased progressively,
      depending on the K+ concentration of above 35 mM. 2. The L-type Ca2+ channel
      blocker, D-600 and nifedipine inhibited the tension development and Mn2+ uptake
      after addition of Mn2+ in the high-K+ (60 mM) medium, however, T-type Ca2+
      channel blocker, Ni2+ and amiloride had no effect on it. 3. D-600 and nifedipine
      inhibited the tension development and Mn2+ uptake in the presence of 5 mM Mn2+ in
      the Ca(2+)-free, high-K+ (60 mM) medium. 4. The results suggest that Mn2+
      penetrates via L-type Ca2+ channels in the ileal cell membrane in a state of
      prolonged depolarization and activates the contractile elements.

PMID- 7590092
TI  - Muscarinic receptor subtypes in the bisected vas deferens of the rat.
AB  - 1. The nature of muscarinic receptor subtypes in the isolated prostatic and
      epididymal segments of the vas deferens of the rat were studied. 2. Presynaptic
      receptors were characterized in segments under neurogenic transmural stimulation;
      postsynaptic receptors in segments without stimulation. 3. The present work
      suggests that the potency of ACh required to activate muscarinic receptors is
      higher in the prostatic than in the epididymal segment. 4. McN-A-343 was only
      able to induce dose-dependent contractions in the prostatic segment. 5. The pA2
      value for 4-DAMP suggests that in the prostatic segment the postsynaptical ACh
      receptors seem to be pharmacologically similar to the ACh-M3 subtype. 6.
      Antagonism of the presynaptic ACh receptor subtype by pirenzepine supports the
      evidence that these receptors belong to the ACh-M1 subtype.

PMID- 7590093
TI  - Thermoregulatory activity of sodium nitroprusside and arginine vasopressin.
AB  - 1. Thermal responses to sodium nitroprusside (SNP, 3 mg/kg/hr) and arginine
      vasopressin (AVP, 3 micrograms/kg) were investigated in normothermic and febrile
      rabbits (LPS, 1 microgram/kg) at ambient temperature of 20.0 +/- 1.0 degrees C.
      Furthermore, blood pressure after these drugs was tested on a separate group of
      animals. 2. I.v. infusion of SNP produced hypothermia and attenuated pyrogen
      fever. On the other hand, AVP increased body temperature and intensified the
      febrile response. 3. Both drugs affected in an opposite way blood pressure, i.e.
      SNP produced falls and AVP increases in this parameter. 4. The relationship
      between the activity of the vascular and thermoregulatory systems in normothermic
      or febrile state is discussed.

PMID- 7590094
TI  - Sensitivity of cardiac tissues with moderate and advanced hypertrophy to calcium
      ions.
AB  - 1. Prolonged existence of hypertension is known to induce a compensatory increase
      in cardiac weight, later followed by a loss of functional responsiveness to
      biological stimuli. 2. It was the aim of the present study to investigate the
      functional responses of hypertrophied hearts to rising levels of intracellular
      calcium. The experiments were performed using two different degrees of cardiac
      hypertrophy, the first as obtained in spontaneously hypertensive rats (SHR) of 18
      20 weeks old, the second by using rats, 32-34 weeks old, with a surgically
      induced stenosis of the thoracic aorta (ASR). The ASR, which showed signs of
      overt heart failure, may be presented as a model for hypertension-induced end
      stage cardiac hypertrophy. Age-matched normotensive Wistar-Kyoto rats (WKY) and
      sham-operated Wistar rats served as respective controls. 3. Different methods
      were employed such as increasing the extracellular Ca2+ concentration,
      stimulation of calcium influx by means of the calcium entry promoter Bay K 8644,
      or altering the sodium-calcium exchange by means of the sodium ionophore
      monensin. 4. The inotropic responses induced by increasing the extracellular Ca2+
      concentration or provoked by the calcium entry promoter Bay K 8644 proved more
      pronounced in hearts taken from SHR of 18 weeks old than in those from
      normotensive control rats, whereas the response to monensin was found to be the
      same in both types of hearts. In the hearts of ASR, however, the inotropic
      responses to Ca2+, Bay K 8644 and monensin were strongly impaired. 5. These data
      demonstrate that in functional experiments the sensitivity to Ca2+, which
      represents the main pathway in establishing a contraction, is strongly reduced in
      advanced cardiac hypertrophy.

PMID- 7590089
TI  - Effect of prenatal allylestrenol treatment (hormonal imprinting) on the serum
      testosterone and progesterone level in adult rats.
AB  - 1. Female rats were treated with allylestrenol on the 15th, 17th and 19th days of
      their pregnancy. 2. Serum testosterone and progesterone level of their three
      months old offspring were higher than control in males and females, respectively.
      3. Serum progesterone levels of females, treated both prenatally and in
      adulthood, does not differ from control values. Serum testosterone level of
      males, treated prenatally and in adulthood, is lower than control. 4. One single
      allylestrenol treatment in adulthood does not make changes in testosterone
      concentration in males, but progesterone level is elevated in females. 5. Our
      experiments draw attention to the dangers of prenatal allylestrenol treatments
      (administered in case of endangered pregnancies) which may have long lasting
      effects on sexual steroid hormone levels.

PMID- 7590097
TI  - Characterization of GABAB ligands in vivo.
AB  - 1. While GABAB antagonists have been examined in vitro, very few have been tested
      in vivo. A range of GABAB antagonists were tested against baclofen-induced muscle
      relaxation and hypothermia. 2. The GABAB antagonists exhibited a range of in vivo
      activity profiles. 3. CGP 35348 showed clear antagonist effects, while BPBA and 4
      ABPA appeared to have agonist properties. 4. Phaclofen, 2-hydroxysaclofen, 3-APPA
      and 9G seemed to have little effect in this system at the doses tested. 5.
      Differences between in vivo and in vitro activity could be explained by
      differences in blood-brain barrier permeability, or possible differences in
      affinities for the sub-classes of GABAB receptors.

PMID- 7590095
TI  - The effect of L-tyrosine on some anti-nociceptive and non-nociceptive actions of
      morphine in mice.
AB  - 1. This work examines the effect of L-tyrosine on the antinociceptive and non
      nociceptive actions of morphine in mice. The antinociceptive action was measured
      using the hot plate method, and the non-nociceptive actions included the effect
      on concentrations of glucose, cholesterol and triglycerides in serum or blood,
      and the effect on gastrointestinal transit time (GITT) and rectal temperature. 2.
      L-tyrosine (25, 50, 100 and 200 mg/kg), subcutaneously (s.c.) dose-dependently
      potentiated the antinociceptive action of morphine (5 mg/kg, s.c.). L-tyrosine
      alone did not produce significant antinociceptive action, nor did it affect any
      of the other non-nociceptive actions measured. 3. Acute administration of
      morphine (5, 10 and 20 mg/kg) produced dose-dependent increases in blood glucose
      concentration which were insignificantly potentiated by L-tyrosine (25-200 mg/kg)
      when given together with morphine. Morphine produced dose-dependent and
      significant decrease in serum triglycerides concentrations, an effect which was
      not influenced by L-tyrosine treatment. Serum cholesterol was not affected by
      treatment with morphine, either alone or when given with L-tyrosine. 4. Morphine
      produced dose-dependent and significant decreases in GITT which was not affected
      with L-tyrosine.

PMID- 7590096
TI  - Propionate modifies lipid biosynthesis in rat peritoneal macrophages.
AB  - 1. This study examines the effect of propionate, normally produced in the gut, on
      lipid metabolism of resident macrophage. This cell is very abundant in the
      epithelial lining of the gut. 2. The activity of propionyl-CoA synthetase in
      macrophages was shown to be 0.39 nmol/min per mg protein, so this cell presents
      the ability to use propionate. Propionate at concentrations varying from 0.5 to 5
      mM did not affect the activities of carnitine acetyltransferase, ATP-citrate
      lyase, acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. 3. Thus this short
      chain fatty acid did not alter the capacity for transferring acetyl-CoA from
      mitochondria to cytosol and for ketone bodies formation and oxidation. However,
      propionate (40 mM) inhibited the incorporation of [1-14C]-palmitate into
      phospholipids, cholesterol, cholesterol ester and triacylglycerol and the
      incorporation of [3-14C]-pyruvate into phospholipids. 4. These findings suggest
      that fibre-rich diet by generating propionate may regulate macrophage lipid
      metabolism.

PMID- 7590101
TI  - The esters of carboxylic nutrients as insulinotropic tools in non-insulin
      dependent diabetes mellitus.
AB  - 1. In non-insulin-dependent diabetes mellitus, the pancreatic B-cell displays a
      preferential impairment of its secretory response to D-glucose. 2. A number of
      agents could be used to restore secretory activity in the diseased B-cell. 3. In
      this respect, esters of carboxylic nutrients, such as succinic or glutamic acid,
      present the advantages of stimulating both proinsulin biosynthesis and insulin
      release, remaining efficient in models of B-cell glucotoxicity, augmenting the
      secretory response to hypoglycemic pharmacological agents, protecting the B-cell
      against cytotoxic aggressions, and exerting a long-term beneficial effect upon
      the secretory potential of the endocrine pancreas. 4. Potential limitations of
      this new therapeutical approach, such as the generation of methanol from the
      esters, their postulated inefficacy after enteral administration, or the
      occurrence of extrapancreatic metabolic effects may be circumvented. 5. The
      esters of carboxylic nutrients could even be used in other cells endangered by
      ATP depletion.

PMID- 7590100
TI  - The effect of topical CCNU(1-(2-chloroethyl)-3 cyclohexyl 1 nitrosurea) treatment
      on lipid peroxidation of glial tumours transplanted on rat brain.
AB  - 1. The effect of topical CCNU treatment on lipid peroxidation of glial tumors
      transplanted on rat brain has been investigated in 22 rats. 2. Four groups have
      been selected as normal brain tissue, normal brain tissue+CCNU, tumour tissue,
      tumour tissue+CCNU. In these groups malondialdehyde (MDA) levels have been
      measured as a marker of lipid peroxidation. 3. Lipid peroxidation was high in
      tumour tissue in respect to controls (P < 0.05). In normal tissues topical CCNU
      treatment caused increase in lipid peroxidation (P < 0.05). In tumor tissues,
      topical CCNU decreased lipid peroxidation (P < 0.05). It is concluded that
      further studies have to be performed in order to determine whether increases in
      lipid peroxidation on CCNU treated normal brain tissues is a result of the
      inhibitory effect on cellular defence systems or promotion of free radical
      production.

PMID- 7590098
TI  - Vasorelaxant effect of the analgesic clonixin on rat aorta.
AB  - 1. A novel vasorelaxant effect of clonixinate of L-lysine (Clx), analgesic and
      anti-inflammatory, was studied in rat aortic rings. 2. Clx completely relaxed
      aortic rings contracted by KCl 70 mM and together with its analog flunixin
      exhibited lesser potency but equal efficacy than verapamil. In comparison,
      indomethacin, which is a more potent cyclo-oxygenase inhibitor relaxed only about
      40% of the maximal contraction of aortic rings. 3. Furthermore, Clx antagonized
      Ca2+ dependent aortic contraction and BAY K-8644 induced aortic contraction
      suggesting its calcium antagonist character. 4. From these results it can be
      concluded that the hypotensive effect seen in rats in vivo after Clx i.v.
      injection arises because of vasodilatory effect of Clx and gives further support
      to the proposal that the pharmacological mechanism of action of Clx should be
      calcium antagonism.

PMID- 7590099
TI  - Serotonin-induced paw edema in the rat: pharmacological profile.
AB  - 1. Serotonin (5-HT) induced a linear increase in paw weight in rats within 1 hr
      of an intraplantar injection (50 microliters vol) over a concentration range of
      0.005-0.2 mg/ml. At the 0.2 mg/ml concentration, a 16-fold increase in paw weight
      was observed as compared to saline-injected controls. 2. Serotonin antagonists,
      such as LY53857, were the most effective antagonists of 5-HT induced paw
      swelling, producing near complete antagonism and an approximate ED50 of 0.1
      mg/kg. A mixed 5-HT/histamine antagonist, cyproheptadine, also produced a nearly
      complete inhibition of the 5-HT response with an approximate ED50 of 1.3 mg/kg.
      3. Dopamine agonists (pergolide, quinpirole), yohimbine, dexamethasone and
      nifedipine also produced a significant degree of antagonism of the 5-HT response.
      4. Clonidine, prazocin, chlorpheniramine, cimetidine, various dopamine
      antagonists, imipramine, cyclosporine A, piroxicam and superoxide dismutase were
      all ineffective at altering the paw swelling response to 5-HT.

PMID- 7590102
TI  - Molecular pharmacology of V1a vasopressin receptors.
AB  - 1. Vasopressin, a mammalian neurohypophysial peptide hormone, has diverse
      physiological actions. 2. Pharmacological studies, using a range of mammalian
      tissues, have identified three subtypes of vasopressin receptor. 3. The V1a
      subtype of vasopressin receptor is widely distributed and mediates many central
      and peripheral actions of vasopressin. 4. The development of subtype-selective
      vasopressin analogues has provided valuable tools for pharmacological and
      physical studies of the V1a receptor protein. 5. Pharmacological differences
      indicate species heterogeneity in the characteristics of V1a receptors and in the
      expression of hepatic V1a receptors. 6. The cloning of neurohypophysial hormone
      receptor proteins allows structural and functional comparison of the V1a
      vasopressin receptors with other G-protein-coupled receptors.

PMID- 7590104
TI  - PEI6, a new basic secretagogue in rat peritoneal mast cells: characteristics of
      polyethylenimine PEI6 resemble those of compound 48/80.
AB  - 1. Polyethylenimine with a molecular weight of 600 (PEI6) was the simplest and
      the most useful to investigate mast cell-activating mechanisms via pertussis
      toxin (IAP)-sensitive G protein pathway. 2. IAP, lidocaine, or dibutyryl cyclic
      AMP were inhibitors of the histamine release induced by PEI6, but anti-allergic
      drug DSCG, the calcium antagonist, D-600, kinase inhibitors, H-7 and K252a, or
      the calmodulin inhibitor, W-7 were not. 3. The additive effects of compound 48/80
      and PEI6 suggested that the action sites for PEI6 overlapped the binding sites of
      compound 48/80. 4. Mast cell activation induced by PEI6 was sugar-specifically
      inhibited by N-acetylglucosamine(Glc-NAc)-specific lectins and/or by sialic acid
      (Sia)-specific lectins, suggesting that the action sites for PEI6 were
      glycoproteins having GlcNAc and/or Sia residues. 5. Four glycoproteins seemed to
      be involved in histamine release, including the IAP-sensitive G-protein pathway.

PMID- 7590105
TI  - beta-Alanyl-L-histidinato zinc and bone resorption.
AB  - 1. beta-Alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to beta-alanyl
      L-histidine, is a new zinc compound. beta-Alanyl-L-histidine can uniquely
      chelated zinc ion in various essential trace metals. More recently, it has been
      demonstrated that this compound has more intensive effect than zinc sulfate on
      bone metabolism, suggesting a role as pharmacological tool in osteoporosis. This
      review describes mainly the action of AHZ on bone resorption as summarized in the
      following. 2. The prolonged oral administration of AHZ (10-100 mg/kg/day) can
      completely prevent bone loss in the femur of ovariectomized rats, indicating the
      preventive effect of AHZ on bone resorption in vivo. 3. The decrease in bone
      calcium content induced by various bone resorbing factors was completely
      inhibited by the presence of AHZ (10(-6)-10(-4) M) in bone tissue culture system
      in vitro. 4. Many bone resorbing agents can stimulate the formation
      (differentiation) of osteoclasts from marrow cells. AHZ (10(-6)-10(-4) M) clearly
      inhibited osteoclast-like cell formation in mouse marrow culture in vitro. 5. AHZ
      may act on the process of parathyroid hormone-induced protein kinase C activation
      which is involved in Ca(2+)-signaling in osteoclastic cells.

PMID- 7590103
TI  - Molecular actions of ebselen--an antiinflammatory antioxidant.
AB  - 1. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a non-toxic seleno
      organic drug with antiinflammatory, antiatherosclerotic and cytoprotective
      properties. 2. Ebselen and some of its metabolites are effective reductants of
      hydroperoxides including those arising in biomembranes and lipoproteins. 3. By
      reactions with hydroperoxides and thiols several interconversion cycles are
      formed which include ebselen metabolites with varying oxidation number of the
      selenium. 4. In the presence of thiols ebselen mimics the catalytic activities of
      phospholipid hydroperoxide glutathione peroxidase. 5. Ebselen inhibits at low
      concentrations a number of enzymes involved in inflammation such as
      lipoxygenases, NO synthases, NADPH, oxidase, protein kinase C and H+/K(+)-ATPase.
      The inhibitions are manifested on the cellular level and may contribute to the
      antiinflammatory potential of ebselen.

PMID- 7590106
TI  - Membrane transport of nucleobases: interaction with inhibitors.
AB  - 1. The kinetic properties and the mechanism of nucleobase transport and transport
      inhibition are briefly reviewed. 2. Many purine derivatives even when bearing
      large substituents on N9 and C6 are inhibitors of nucleobase transport, some are
      also substrates. 3. Papaverine and other benzyl-isoquinolines are efficient
      inhibitors of facilitated transport of nucleobases. 4. Papaverine is a
      noncompetitive inhibitor of nucleobase transport in human erythrocytes. 5.
      Reduction of the aromatic isoquinoline to the tetrahydro form causes loss of
      inhibitory activity whereas replacement of methoxy groups by ethoxy groups leads
      to increased activity. 6. Papaverine also inhibits sodium dependent active
      nucleobase transport in pig kidney cells. 7. The nucleoside transport inhibitors
      dipyridamole and dilazep have no effect on facilitated diffusion transport of
      nucleobases, but inhibit in micromolar concentrations active sodium dependent
      nucleobase transport in pig kidney cells.

PMID- 7590108
TI  - The nocturnal polyuria syndrome (NPS).
AB  - 1. The nocturnal polyuria syndrome (NPS) is characterized by an increased
      nocturnal urine output. The diurnal rhythm in the antidiuretic hormone (ADH)
      system is absent, and often there is no detectable ADH in the plasma at all
      during the night. The 24-hr urine output is normal or only moderately increased.
      Men without nocturnal micturition, normally have a substantial increase in their
      nocturnal plasma ADH, while those with a need to micturate during the night have
      the same ADH level at night as in the daytime. Women have lower ADH levels than
      men, and no nocturnal increase in ADH irrespective of nocturnal voiding. Subjects
      with an increased nocturnal voiding frequency due to increased nocturnal urine
      output have an increased thirst, most markedly at night. They often avoid
      drinking in the evening, but they are unable to resist the impulse to drink
      during the night. People with polyuria at night wake up often because of the need
      to void, and accordingly are often tired during the day. 2. An increased
      nocturnal urine output can be reduced by administration of desmopressin at night.
      In a short-term study of elderly sufferers from NPS, treated with 20 micrograms
      desmopressin as nose drops in the evening the nocturnal urine output was reduced
      from 65 +/- 8% of the 24-hr urine output before treatment to 50 +/- 15% during
      treatment. In another study elderly with NPS were treated with 40 micrograms
      desmopressin as an intranasal aerosol in the evening.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7590109
TI  - Recent advances in pharmacognosy research in China.
AB  - 1. Progress made in pharmacognostic research by Chinese investigators in the last
      decade is summarized herein. 2. This review covers studies on herbal properties,
      resources, identification, physicochemical evaluation, cultivation, breeding,
      tissue culture, collection, processing, preparation, active principles and
      pharmacological activities of traditional and herbal Chinese drugs. 3. As a
      result of these research activities errors in species identification were
      spotted, new drug resources were revealed, new taxa were discovered, crude drugs
      were analyzed qualitatively and quantitatively, optimal conditions for
      cultivation and breeding of plants and animals used as drugs were formulated, the
      quality of some drugs was controlled, the drug processing procedures and storage
      conditions were evaluated, and the chemistry and pharmacology of a number of
      crude drugs were elucidated.

PMID- 7590107
TI  - The use of the human neuroblastoma SH-SY5Y to study the effect of second
      messengers on noradrenaline release.
AB  - 1. Recent data suggesting that the human neuroblastoma SH-SY5Y is a suitable cell
      line in which to study the effect of second messengers on NA release are
      discussed in the context of current views on exocytosis. 2. Release of NA is
      evoked by depolarization, as well as activation of muscarinic (M3) and bradykinin
      (B2) receptors in SH-SY5Y cells which have not been differentiated by the
      addition of growth factors. 3. Evoked release is enhanced by activation of
      protein kinase C. 4. Activation of protein kinase C decreases the changes in
      intracellular calcium evoked by carbachol, bradykinin and 100 mM K+. 5. SH-SY5Y
      express N-type and L-type voltage sensitive Ca2+ channels. L-Type Ca(2+)-channels
      are coupled to NA release under conditions of weak depolarization. However with
      strong depolarization (100 mM K+) both L-type and N-type channels are involved.
      6. Muscarinic- and neuropeptide Y receptors are coupled to the inhibition of Ca2+
      channel activity.

PMID- 7590110
TI  - REM sleep deprivation treatment enhances the effect of clozapine in the forced
      swimming test.
AB  - 1. Effect of REM sleep (REMs) deprivation treatment on clozapine response in the
      forced swimming test was investigated. 2. Clozapine significantly increased the
      swimming activity in REMs-deprived mice at a dose of 5 mg/kg (i.p.) which did not
      affect the activities in the control groups. 3. Physostigmine (0.3 mg/kg, i.p.),
      an acetylcholinesterase inhibitor, blocked the increasing effect of 5 mg/kg
      clozapine on swimming activity in REMs-deprived animals. 4. These results suggest
      that the REMs deprivation treatment-induced enhancement of effect of clozapine on
      swimming activity is mediated by the functional change of central cholinergic
      system following the treatment.

PMID- 7590111
TI  - Age-related changes in [3H]baclofen binding in mouse cerebellum.
AB  - 1. Specific [3H]baclofen binding to cerebellar membranes from 1-month-old
      (young), 8-month-old (older) and 20-month-old (aged) mice was lower than that to
      membranes from 3-month-old mice (mature adult), whereas in cerebral cortical
      membranes there were no age-related changes in [3H]baclofen binding among the
      four age groups. 2. Scatchard analysis revealed that the density of cerebellar
      GABAB receptors significantly decreased during aging. 3. There were no age
      related changes in the inhibitory effect of Gpp(NH)p on [3H]baclofen binding. 4.
      These results suggest that the characteristics of GABAB receptors in the
      cerebellum change during aging without any alteration in the coupling of the
      receptor to guanine nucleotide regulatory proteins.

PMID- 7590113
TI  - Exacerbation of acetaminophen hepatotoxicity by thalidomide and protection by
      nicotinic acid amide.
AB  - 1. The effects of racemic thalidomide (D[+]/L[-] alpha-phthalimido-glutarimide)
      on acetaminophen (AAP)-induced hepatitis were tested in male NMRI mice (n = 133)
      and quantified as serum activities of glutamate-oxaloacetate transaminase (GOT)
      and glutamate-pyruvate transaminase (GPT). 2. A 2.1-fold increase of GOT and a
      1.9-fold increase of GPT activities (P < 0.001) were observed in mice treated
      perorally with 500 mg/kg of AAP plus 150 mg/kg of thalidomide (Thal). In the
      absence of AAP, Thal did not display any detectable hepatotoxic effects. 3. The
      Thal-induced exacerbation of AAP hepatotoxicity was completely inhibited by
      nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP)
      (P < 0.0001), suggesting a possible influence of Thal on the hepatic metabolism
      of NAD-adenoribosylation. 4. We see the main application of nicotinic acid amide
      as for the combinational use in pharmaceutical preparations of AAP in order to
      avoid hepatic damage in patients treated with AAP and Thal.

PMID- 7590112
TI  - Age-dependent changes in voltage-gated calcium channels and ATP-dependent
      potassium channels in Fischer 344 rats.
AB  - 1. Radioligand binding and 45Ca2+ uptake measurements quantitated ion channel
      numbers and properties in brain membranes from Fischer 344 rats at 6, 12, 18 and
      30 months of age. 2. Decreases in 1,4-dihydropyridine density occurred in
      striatum, hippocampus and cortex with a decreased affinity. 3. Decreases in w
      conotoxin binding occurred in hippocampus and striatum with an increase in
      affinity. 4. K+ depolarization-mediated 45Ca2+ uptake decreased only in striatum
      at 18 months. 5. Decreases in glibenclamide binding occurred in cortex and
      cerebellum at 12-30 months. 6. No changes in 1,4-dihydropyridine binding occurred
      with age in heart, but glibenclamide binding density was significantly decreased
      at 30 months.

PMID- 7590114
TI  - Involvement of sodium/calcium exchange in the diclofenac-induced spasmolytic
      effect on rat uterus.
AB  - 1. The effect of diclofenac (10-100 microM) on rat uterus contraction and its
      modification by ouabain (0.1 mM), amiloride (0.1 and 1 mM), ouabain (0.1 mM) plus
      amiloride (1 mM) and the replacement of sodium by choline have been assayed. 2.
      Diclofenac produces dose-dependent relaxation of vanadate (0.3 mM)-induced
      contraction (EC50, 17.3 +/- 1.8 microM). This effect is significantly reduced in
      choline medium (EC50, 49.1 +/- 4.5 microM) and by ouabain in sodium-medium (EC50,
      52 +/- 7 microM). 3. Amiloride displaces, in a dose-dependent way, the diclofenac
      induced relaxant effect. However, ouabain plus amiloride did not produce a
      sinergic effect. 4. Our results suggest that diclofenac produces relaxation of
      vanadate-induced contraction by activation of Na+/Ca(2+)-exchange.

PMID- 7590115
TI  - Effects of nifedipine ryanodine and cyclopiazonic acid on tension development of
      ileal longitudinal muscle by manganese ions in Ca(2+)-free high-K+ medium.
AB  - 1. Mn2+ (5 mM) could evoke the contraction in a Ca(2+)-free, high-K+ (60 mM)
      medium in ileal longitudinal muscle. Nifedipine, L-type Ca2+ channel blocker,
      inhibited dose-dependently both the contraction and manganese uptake in the
      presence of 5 mM Mn2+, in the Ca(2+)-free, high-K+ medium. 2. However, both
      ryanodine, Ca2+ release blocker from SR and cyclopiazonic acid, specific SR
      Ca(2+)-ATPase blocker, had no effects on the contractions evoked by Mn2+ and the
      manganese uptake in the Ca(2+)-free, high-K+ medium. 3. These results suggest
      that Mn2+ did not liberate Ca2+ at the storage sites during the Mn(2+)-induced
      contraction in Ca(2+)-free, high-K+ medium. Mn2+ is entering via voltage
      dependent Ca2+ channels in the ileal cell membranes and it directly activates the
      contractile elements.

PMID- 7590117
TI  - Characterization of 5-hydroxytryptamine receptors in goat cerebral arteries.
AB  - 1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT,
      10(-8)-3 x 10(-5) M) elicited concentration-dependent contractions with EC50 =
      2.1 (1.9-2.5) x 10(-7) M and Emax = 64 +/- 2% of 50 mM KCl-induced contraction.
      2. Several 5-HT receptor agonists were used: (a) the agonist of 5-HT2 receptors
      alpha-methyl-5-hydroxy-tryptamine (10(-7)-3 x 10(-4) M) induced strong
      contraction (51 +/- 6%); (b) the selective agonists of 5-HT1 receptors
      sumatriptan (10(-8)-10(-5) M) and 5-carboxamidotryptamine (10(-9)-10(-4) M) and
      the agonist of 5-HT1A receptors 8-hydroxy-2-(di-n-propylamino)tetralin (10(-7)-3
      x 10(-5) M) induced weak contractions (8, 18 and 14%, respectively); and (c) the
      agonist of 5HT3 receptors 2-methyl-5-hydroxytryptamine (3 x 10(-6)-10(-4) M)
      induced almost negligible contraction. 3. Pretreatment with the antagonist of 5
      HT1A and 5-HT1B receptors cyanopindolol (10(-8), 10(-6) M), the antagonist of 5
      HT1/5-HT2 receptors methysergide (10(-11), 10(-9) M) and the antagonist of 5-HT2
      receptors ketanserin (10(-11), 10(-9) M) induced non-competitive inhibition of
      the concentration-response curve to 5-HT. The antagonist of 5-HT3 receptors 3
      trophanyl-3,5-dichlorobenzoate (10(-7), 10(-5) M) did not inhibit the contractile
      curve to 5-HT. 4. These results suggest that 5-HT contracts the goat middle
      cerebral artery by acting mainly on 5-HT2 receptors.

PMID- 7590116
TI  - Hepatoprotective reactivity of a copper-di-Schiffbase active centre analogue of
      Cu2Zn2 superoxide dismutase.
AB  - 1. The anti-inflammatory and hepatoprotective efficacy of CuPu(Py)2 ((N,N'-bis(2
      pyridyl-methylene)-1,4-butanediamine) (N,N',N",N")-Cu2+), a serum-stable, copper
      di-Schiffbase active centre analogue of Cu2Zn2 superoxide dismutase was tested in
      male NMNR mice suffering from endotoxin/galactosamine-induced hepatitis. 2.
      Parameters including the activities of serum transaminases and sorbitol
      dehydrogenase as well as the levels of reactive oxygen and nitrogen intermediates
      which were used to quantify the disease activity. 3. A dose-dependent inhibition
      of hepatic enzyme release was noted in the presence of 0.1-10 mg/kg of CuPu(Py)2.
      4. The release of transaminases from damaged liver cells was reduced by 68% and
      paralleled the reduction of serum levels of nitric oxides. 5. Elevated levels of
      reactive oxygen species were normalized to those healthy controls. 6. The copper
      free apochelate Pu(Py)2, which is unable to dismutate superoxide, did not display
      any anti-inflammatory reactivity.

PMID- 7590118
TI  - Altered methadone analgesia due to changes in plasma protein binding: role of the
      route of administration.
AB  - 1. The effect of experimental inflammation on methadone analgesia was evaluated
      in rats, by the tail-flick test, after single intravenous (0.35 mg/kg) and
      subcutaneous (3 mg/kg) doses. 2. After i.v. administration a significant decrease
      (P < 0.05) in the area under the methadone time-response curve was seen in rats
      with experimental inflammation, when compared with control. However, no
      differences in the analgesic response to methadone were detected between control
      rats and rats with inflammation when the drug was administered by s.c. injection.
      3. Plasma mucoprotein levels were significantly increased (P < 0.001) and
      methadone free fraction was significantly decreased in rats with inflammation (P
      < 0.05). In addition, after i.v. methadone a decrease in brain uptake in rats
      with inflammation was detected. A significant correlation between brain uptake
      index and plasma free fraction was also observed. 4. These results suggest that a
      decreased immediate response to i.v. methadone may occur in circumstances in
      which there is an increase in alpha 1 acid glycoprotein, but that this is not
      likely to be observed when the absorption is not instantaneous.

PMID- 7590119
TI  - Central and peripheral dopamine D1/DA1 receptor modulation of gastric secretion
      and experimental gastric mucosal injury.
AB  - 1. Dopamine D1 (central)/DA1 (peripheral) receptors are believed to influence
      gastrointestinal function and pathology. 2. When given i.c.v. or i.p., an agonist
      (SKF38393) and an antagonist (SCH23390) of this DA receptor subtype inhibit and
      enhance, respectively, gastric secretion and gastric mucosal injury. 3. When
      given both i.c.v. and i.p., their respective effects in the gut were amplified.
      4. Antagonist or agonist given i.p., blocked the corresponding protective and
      worsening effect of the agonist or antagonist given i.c.v. 5. Both central and
      peripheral D1/DA1 receptors modulate gastric function and response to injury.

PMID- 7590120
TI  - Influence of hormonal status in relaxant effect of diethylstilbestrol and
      nifedipine on isolated rat uterus contraction.
AB  - 1. The effects of diethylstilbestrol (DES, 10(-7)-10(-5) M) and nifedipine (10(
      10)-10(-7) M) on KCl (60 mM)-induced tonic contraction in the uterus of
      ovariectomized and 17 beta-estradiol (0.1 mg/kg/day, s.c.)-, 17 alpha-estradiol
      (0.1 mg/kg/day, s.c.)-, or progesterone (2 mg/kg/day, s.c.)-treated rats have
      been assayed. 2. The dose-dependent relaxation produced by nifedipine in
      ovariectomized rats (EC50 = 5.59 +/- 1.25 x 10(-9) M) is potentiated in uterus of
      rats treated with 17 beta-estradiol and progesterone (EC50 = 0.59 +/- 0.1 and
      0.49 +/- 0.1 x 10(-9) M, respectively) but not in the 17 alpha-estradiol-treated
      rats (3.01 +/- 0.6 x 10(-9) M). 3. The relaxation produced by DES on
      ovariectomized rats (EC50 = 0.84 +/- 0.14 x 10(-6) M) is reduced when the rats
      are treated with 17 beta-estradiol (EC50 = 2.22 +/- 0.2 x 10(-6)M) or
      progesterone (EC50 = 1.24 +/- 0.08 x 10(-6) M), but unmodified by 17 alpha
      estradiol (EC50 = 0.58 +/- 0.01 x 10(-6) M). 4. The nifedipine-induced relaxation
      is reversed with Bay K 8644 (10(-10)-10(-6) M) in all experimental conditions.
      However, Bay K 8644 counteracted the relaxation of DES at 45.7% on ovariectomized
      rats but this was lower than 30% in the other groups. 5. Our results suggest that
      in ovariectomized rats the effects of both nifedipine and DES are similar, but 17
      beta-estradiol and progesterone produce a contrary effect on the relaxation
      induced by nifedipine and DES (by increasing the nifedipine and decreasing the
      DES effects).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7590121
TI  - Noradrenergic vasorelaxation of porcine coronary arteries is enhanced by direct,
      acute exposure to 17 beta-estradiol.
AB  - 1. We tested whether responses of isolated coronary arteries to adrenergic agents
      are altered by overnight (18-22 hr) or acute exposure to physiological levels of
      17 beta-estradiol. 2. Sensitivity to relaxation by norepinephrine (-log M ED50)
      was enhanced significantly in isolated arteries after acute exposure to 10(-9) M
      17 beta-estradiol. Neither alpha-adrenergic contraction to norepinephrine, nor
      beta-adrenergic relaxation to isoproterenol was affected by acute exposure to 17
      beta-estradiol. 3. Responses of coronary arteries to relaxation or contraction by
      norepinephrine, as well as relaxation by isoproterenol, were not altered by
      overnight incubation with 17 beta-estradiol or by removal of the endothelium. 4.
      We conclude that relaxation of coronary arteries by norepinephrine is enhanced by
      acute, direct exposure to physiological levels of 17 beta-estradiol. This
      enhancement does not result from effects of estradiol to suppress alpha
      adrenergic contraction to norepinephrine or increase coronary beta-adrenergic
      receptor sensitivity.

PMID- 7590122
TI  - Effects of diltiazem and verapamil on ADP-induced rabbit platelet shape change
      and aggregation.
AB  - 1. The effects of diltiazem and verapamil (two structurally different calcium
      channel blockers) were examined on the rabbit platelets shape change and
      aggregation induced by adenosine-5'-diphosphate (ADP). 2. ADP was a much more
      potent stimulator on inducing platelet shape change (ED50 = 1 x 10(-7)) than
      platelet aggregation (ED50 = 1.78 x 10(-6)). 3. Both drugs similarly inhibited
      ADP-induced platelet shape change and aggregation at concentrations more than 300
      microM. 4. There were no significant differences in inhibitory effects of either
      diltiazem or verapamil on ADP-induced platelet shape change and aggregation. 5.
      The inhibitory effects of diltiazem and verapamil on ADP-induced platelet shape
      change and aggregation at high concentrations may be due to their non specific
      properties.

PMID- 7590123
TI  - The effect of 5-HT3 receptor antagonists on the writhing response in mice.
AB  - 1. The ability of several 5-HT3 receptor antagonists (MDL 72,222EF, the methyl
      quaternary ammonium salt of MDL 72,222, dolasetron, tropisetron, granisetron and
      ondansetron) to inhibit writhing induced in the mouse by either 5
      hydroxytryptamine (5-HT), acetylcholine or acetic acid was examined. 2. All of
      the 5-HT3 receptor antagonists were able to inhibit writhing induced by
      acetylcholine. MDL 72,222EF and tropisetron were also able to inhibit writhing
      induced by 5-HT and acetic acid but higher doses were required to have the same
      effect as against acetylcholine. Dolasetron inhibited writhes induced by 5-HT but
      failed to significantly affect writhes induced by acetic acid. 3. MDL 72,222EF
      and its quaternary salt were more potent and had a more rapid onset of action
      after i.p. than after s.c. administration. 4. 2-Methyl-5-HT did not induce
      writhing at doses up to 4 mg/kg i.p., whereas 5-HT dose-dependently induced
      writhing over the range 0.5-2 mg/kg. 5. These results show that 5-HT3 receptor
      antagonists can inhibit writhes induced by a variety of compounds and this
      appears to be a local action. However, the inability of 2-methyl-5-HT to induce
      writhing and the high doses of antagonist required indicate that further studies
      are required to establish a role for 5-HT3 receptors in this effect.

PMID- 7590124
TI  - Effects of methylene blue and ascorbate on transmembrane potential in frog
      skeletal muscle.
AB  - 1. The effects of methylene blue (MB, 10(-4) M) and ascorbate (ASC, 10(-4) M) on
      the resting membrane potential of frog skeletal muscle fibers were studied in Cl(
      )-free medium at various external K+ concentrations. 2. Muscle fibers formed two
      distinct populations according to their resting potentials (hyperpolarized to 
      104 mV or depolarized to -31 mV) after a 90 min period of K+ withdrawal. ASC
      increased the relative contribution of hyperpolarized fibers, while in the
      presence of MB, all fibers depolarized during the 90 min of K+ withdrawal. 3. In
      the presence of 2.5 mM K+, ASC had no significant effect on the resting
      potential, while MB moved half of the fibers into the depolarized pool. Elevation
      of [K+]0 to 10 mM caused repolarization of all previously depolarized fibers (to 
      63 mV) in spite of the continuous presence of MB. 4. Ionic currents were measured
      during a 60 mV depolarization step using the double sucrose-gap technique. MB
      significantly increased the peak inward current, while ASC had no effect. The
      steady-state outward current was not affected by MB or ASC. 5. The results
      suggest that ionic conductances may be under redox control in frog skeletal
      muscle.

PMID- 7590125
TI  - Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)
      propionate. I. Secretory and cationic aspects.
AB  - 1. Sodium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD
      1229) is a newly introduced non-sulphonylurea insulinotropic agent. 2. It failed
      to affect insulin release by rat islets incubated in the absence of D-glucose,
      slightly increased insulin output at 2.8 mM D-glucose and markedly enhanced
      secretion at 6.0 and 11.1 mM D-glucose. At the latter hexose concentration, the
      threshold concentration for the insulinotropic action of KAD-1229 was below 0.1
      microM and a close-to-maximal response recorded with 1.0 microM KAD-1229. Even at
      16.7 mM D-glucose, KAD-1229 (10 microM) still augmented insulin output. 3. At 6.0
      mM D-glucose, KAD-1229 (0.1-1.0 microM) caused a concentration-related increase
      in 45Ca uptake. This coincided, in prelabelled islets, with a rapid and dual
      change in 86Rb outflow and dramatic increase in 45Ca outflow. 4. KAD-1229 also
      increased insulin release evoked by 2-ketoisocaproate (10 mM), albeit to a lesser
      extent than observed at a D-glucose concentration of comparable insulinotropic
      efficiency. 14C-labelled KAD-1229 was poorly oxidized by the islets. 5. These
      findings support the view that the mode of action of KAD-1229 displays analogy
      with that of hypoglycemic sulphonylurea.

PMID- 7590126
TI  - Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)
      propionate. II. Ionophoretic and conformational aspects.
AB  - 1. The non-sulphonylurea insulinotropic agent sodium (2S)-2-benzyl-3-(cis
      hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) was found to display
      calcium ionophoretic activity in an artificial membrane model. 2. Conformation
      analysis indicated that a complex between calcium and KAD-1229, with a 1:2
      stoichiometry, indeed displays favourable attributes for ionophoretic activity
      across a hydrophobic environment. 3. It is speculated that the ionophoretic
      property of KAD-1229 might participate to the remodelling of cationic fluxes
      evoked by this insulinotropic agent in pancreatic islet cells.

PMID- 7590127
TI  - The effect of AL0671, a novel potassium channel opener, on potassium current in
      rat aortic smooth muscle cells.
AB  - 1. We evaluated the mechanism of activation by AL0671, a novel potassium channel
      opener, of potassium current in rat aortic smooth muscle cells. 2. Under
      conditions of whole cell recording, AL0671 (1-1000 microM) markedly increased
      potassium current with a Hill coefficient of 2 and dissociation constant of 1.5 x
      10(-4) M. This activation was completely inhibited by intracellular ATP. 3. Under
      inside-out patch conditions, the ATP-sensitive K+ channels (KATP) treated with
      AL0671 (100 microM) showed prolongation of the slower open time component and
      shortening of the slower closed time component without modification of channel
      conductance.

PMID- 7590129
TI  - Effects of pirarubicin in comparison with epirubicin and doxorubicin on the
      contractile function in rat isolated cardiac muscles.
AB  - 1. We have examined the effects of pirarubicin (THP), compared with epirubicin
      (EPI) and doxorubicin (DXR), on the contractile function in papillary muscles
      isolated from rats. 2. In in vivo experiments, in which the rat was treated once
      a week for 4 weeks with DXR (total dose 10 mg/kg) and thereafter once a week for
      4 weeks with THP, EPI or DXR (total dose 10 mg/kg), a positive instead of
      negative force-frequency relationship was observed in the muscles treated with
      EPI and DXR, but not with THP, and an increase in contractile response to
      extracellular Ca2+ was observed more markedly in the muscles treated with DXR
      than in those treated with EPI and THP. 3. In in vitro experiments, in which the
      muscle preparations were incubated with the drugs at 100 or 200 microM for 2 hr,
      EPI and DXR caused a negative inotropic effect and a prolongation of tension
      duration, while THP caused a slight positive inotropic effect and a slight
      prolongation of tension duration. 4. Furthermore, a decrease in the potentiated
      postrest contraction was observed more markedly in the muscles incubated with EPI
      and DXR at 200 microM than in those with THP. 5. These results suggest that both
      EPI and DXR show a cardiotoxicity by impairing the function of cardiac
      sarcoplasmic reticulum, and that the switching of the treatment from DXR to THP
      produces less impairing effects.

PMID- 7590130
TI  - Effects of diltiazem and its analogue siratiazem on contraction and 45Ca2+ uptake
      in sheep coronary artery rings.
AB  - 1. Siratiazem, an analogue of diltiazem designed to be resistant to N
      demethylation, was compared with diltiazem for inhibition of Ca(2+)-induced
      contraction of depolarized coronary artery rings from the sheep. There was no
      significant difference in potency between siratiazem and diltiazem in the
      presence of normal physiological salt solution (IC25 for siratiazem 0.13 +/- 0.04
      microM and for diltiazem 0.08 +/- 0.02 microM) or one mimicking some of the
      conditions that occur during myocardial ischaemia (hypoxia, acidosis, reduced
      glucose and addition of lactate). 2. K(+)-stimulated 45Ca2+ uptake in coronary
      artery rings was also inhibited by siratiazem and diltiazem with similar
      potencies. 3. It is concluded that siratiazem inhibits Ca2+ entry in coronary
      vascular smooth muscle equipotently with diltiazem and that this effect is not
      modified by some of the changes that occur during myocardial ischaemia.

PMID- 7590128
TI  - Identification of a hyperpolarization-activated inward current in uterine smooth
      muscle cells during pregnancy.
AB  - 1. Rat uterine smooth muscle possesses spontaneous contraction and automaticity.
      This study was exerted to examine one of the underlying currents that may be
      involved in the generation of spontaneous activity, the hyperpolarization
      activated inward current. 2. Whole-cell patch clamp experiments were performed on
      freshly-isolated single longitudinal smooth muscle cells of pregnant rat uterus
      (18-day gestation). The holding potential was -30 mV, and long-duration (3 sec)
      hyperpolarizing pulses were applied to -40 to -120 mV. Experiments were performed
      at room temperature (22 degrees C). 3. A hyperpolarization-activated inward
      current (I(f)) was produced at the larger hyperpolarizing steps. Its current
      density (at -120 mV) was -1.03 +/- 0.31 pA/pF (n = 5). The average cell
      capacitance was 64.3 +/- 12.3 pF (n = 8). The threshold potential for activation
      of I(f) was about -70 mV, and the reversal potential was -18.6 +/- 2.1 mV (n =
      4). In the presence of Cs+ (3 mM), the I(f) current (at -120 mV) was decreased by
      76.5 +/- 2.1% (n = 5, P < 0.01). 4. These results indicate that the Cs(+)
      sensitive hyperpolarization-activated inward current is present in the
      longitudinal muscle cells of pregnant rat uterus. This I(f) current may
      contribute to some extent to the electrogenesis of the spontaneous activity.

PMID- 7590131
TI  - Treatment with acarbose, an alpha-glucosidase inhibitor, reduces increased
      albumin excretion in streptozotocin-diabetic rats.
AB  - 1. We examined the effect of the alpha-glucosidase inhibitor acarbose on urinary
      albumin excretion (UAE) in streptozotocin diabetic rats. 2. Treatment with
      acarbose for 8 weeks after induction of diabetes prevented the significant
      increase in UAE observed in untreated diabetic rats relative to nondiabetic
      controls. 3. Acarbose significantly reduced integrated glycemia, which correlated
      with albumin excretion rates, and exerts a salutary effect on diabetic renal
      dysfunction.

PMID- 7590134
TI  - Effects of repeated treatments with an extract of Ginkgo biloba (EGb 761) on
      cerebral glucose utilization in the rat: an autoradiographic study.
AB  - 1. The autoradiographic method based on 2-deoxy-D[1-14C]glucose ([14C]DG) was
      used to determine glucose utilization in 49 discrete structures of rat brain
      under control conditions and after the animals had received repeated treatment
      with an extract of Ginkgo biloba (EGb 761). 2. Oral administration of EGb 761 (50
      or 150 mg/kg/day) to adult male rats for 15 days did not modify body weight, mean
      arterial blood pressure, the concentrations of glucose or hemoglobin in blood,
      blood gases or arterial pH. 3. EGb 761 treatments produced only slight-to
      moderate changes in glucose utilization in the various brain structures; i.e.
      decreases to an extent not exceeding 18.4% at the 50 mg/kg dose or 11.7% at the
      150 mg/kg dose. 4. Glucose utilization was significantly decreased only in the
      frontoparietal somatosensory cortex, nucleus accumbens, cerebellar cortex and
      pons and only with the 50 mg/kg dose of EGb 761. 5. Although the four brain
      structures affected by EGb 761 treatment do not, in themselves, constitute a
      specific functional system of the CNS, these effects appear useful in explaining
      mechanisms underlying the clinical use of EGb 761 in treating problems associated
      with deficient somatosensory processing (e.g. impairment of "vigilance") and
      vestibular mechanisms (e.g. vertiginous syndromes).

PMID- 7590132
TI  - Lymphoproliferative activity of methimazole: free SH group dependency.
AB  - 1. The comparative effects of methimazole (MTI), an antithyroid drug, and its S
      methyl derivate (MMTI), were studied in vitro on the lymphoproliferative response
      to lectin in order to point out the free SH group importance. The cell cycle
      analysis was performed by flow cytometry after cellular DNA staining by propidium
      iodide. 2. We showed that MTI enhanced the PHA-induced DNA synthesis phase (P <
      0.05 from 1 to 100 microns) whereas MMTI had no significant activity. The free SH
      group seems to be necessary to the MTI immunomodulatory activity.

PMID- 7590135
TI  - High potassium-evoked release of ATP from rabbit pulmonary artery via endogenous
      noradrenaline.
AB  - 1. High potassium 30 mM and noradrenaline at 10 microM significantly evoked the
      release of ATP and produced remarkable vasoconstriction in the rabbit pulmonary
      artery. 2. Phentolamine and prazosin at 0.1 microM inhibited ATP release but not
      vasoconstriction by 30 mM potassium. 3. 30 mM potassium significantly evoked the
      release of noradrenaline. 4. There was a significant positive correlation between
      the amounts of release of total purines, sum of ATP, ADP, AMP and adenosine, and
      noradrenaline evoked by 30 mM potassium. 5. 30 mM potassium-evoked ATP release
      was significantly reduced by denudation of endothelium.

PMID- 7590136
TI  - Inhibitory effect of flumequine, enoxacin and norfloxacin on the GABA-induced
      contractile effect on the guinea pig ileum.
AB  - 1. In the present study the effect of flumequine, enoxacin and norfloxacin on the
      GABA-elicited contractions (EC50 1.10 x 10(-5) M) on the isolated guinea pig
      ileum was investigated, in a comparative manner. 2. All three fluoroquinolones
      dose-dependently antagonised the GABA-induced contractions in a non-competitive
      manner, but no statistical difference in the degree of the antagonism they
      produced was noted. Besides, they did not influence the ileal cholinergic
      contractions induced by exogenous acetylcholine. 3. These results suggest that
      the above fluoroquinolones tested dose-dependently inhibit the contractile effect
      of GABA on the guinea pig ileum and this inhibition seems to be associated with
      an antagonistic action of the fluoroquinolones at GABAA-receptors present in the
      guinea pig ileum.

PMID- 7590133
TI  - The analgesic effect of clonixine is not mediated by 5-HT3 subtype receptors.
AB  - 1. The analgesic effect of clonixinate of L-lysine (Clx) in the nociceptive C
      fiber reflex in rat and in the writhing test in mice is reported. 2. Clx was
      administered by three routes, i.v., i.t. and i.c.v., inducing a dose-dependent
      antinociception. 3. The antinociceptive effect of Clx was 40-45% with respect to
      the control integration values in the nociceptive C-fiber reflex method. 4. The
      writhing test yielded ED50 values (mg/kg) of 12.0 +/- 1.3 (i.p.), 1.8 +/- 0.2
      (i.t.) and 0.9 +/- 0.1 (i.c.v.) for Clx administration. 5. Ondansetron was not
      able to antagonize the antinociception response of Clx in the algesiometric tests
      used. 6. Chlorophenilbiguanide did not produce any significative change in the
      analgesic effect of Clx in the nociceptive C-fiber reflex method. 7. It is
      suggested that the mechanism of action of the central analgesia of Clx is not
      mediated by 5-HT3 subtype receptors.

PMID- 7590138
TI  - Effect of dimethyl sulfoxide (DMSO) on the electrocardiogram (ECG) in freely
      moving male Balb/c mice.
AB  - 1. Since dimethyl sulfoxide (DMSO) is a solvent which is often used for drugs in
      animal studies, we investigated the effect of a daily administration of DMSO on
      the telemetrically obtained electrocardiogram (ECG) in freely moving male Balb/c
      mice. 2. During treatment with 4.5 ml 100% DMSO/kg i.p. 5 days per week during 3
      weeks, DMSO caused substantial cardiotoxicity. The ST-interval increased
      significantly after 1 week by 2.2 +/- 1.3 msec and also the ECG wave form changed
      completely in time. 3. During treatment with 4.5 ml 50% DMSO/kg i.p. 5 days per
      week during 3 weeks, no significant difference was observed compared with the
      control animals. 4. During the entire study the maximal heart rate and body
      weight remained constant in all treated groups. 5. The data indicate that DMSO
      can not be used in a 100% concentration to dissolve compounds that are tested for
      protection against the cardiotoxicity of cytostatics.

PMID- 7590137
TI  - The effects of PGE2 and PGF2 alpha on rhythmic contractions of sphincter of Oddi.
AB  - 1. Spontaneous rhythmic activity observed in some of the guinea-pig sphincter of
      Oddi preparations was completely abolished by PGE2 (10(-8) M) but not altered by
      PGF2 alpha (10(-6) M). 2. Indomethacin (10(-5) M), a cyclooxygenase inhibitor,
      elicited long-lasting rhythmic contractions in 50% of the preparations tested,
      which did not show any spontaneous activity. PGE2 (10(-8) M) completely
      inhibited, however PGF2 alpha (10(-8)-10(-6) M) did not change the rhythmic
      contractions induced by indomethacin. 3. Both initial phasic contraction and the
      frequency and amplitude of peristaltic waves induced by ACh (10(-3) M) were
      increased by indomethacin (10(-5) M), decreased by PGE2 (10(-7) M) and not
      altered by PGF2 alpha (10(-7) M).

PMID- 7590139
TI  - Platelet aggregation and atrial natriuretic peptide.
AB  - 1. Isolated human platelets were used to investigate the effect of atrial
      natriuretic peptide (ANP) on in vitro platelet aggregation induced by
      epinephrine, ADP, collagen and 5-hydroxytryptamine. As a direct stimulant of
      particulate guanylate cyclase, ANP is known to have no direct effect on platelets
      which contain soluble guanylate cyclase. 2. In our experiments ANP inhibited
      epinephrine- and partially ADP-induced aggregation in vitro and this effect was
      suggested to be the result of an interaction of the peptide with adenylate
      cyclase in platelets. However, the concentrations required to produce this effect
      were higher than those expected to be found in the circulation both
      physiologically and pathologically. 3. We therefore conclude that though the
      peptide may inhibit-aggregation via adenylate cyclase activation, it is unlikely
      that ANP may play a direct role in preventing platelets aggregating.

PMID- 7590140
TI  - The effect of omeprazole on human natural killer cell activity.
AB  - 1. Omeprazole, an antiulcer drug, inhibits the gastric acid pump via blocking the
      parietal cell (H+ + K+)-ATPase. Omeprazole was also reported to have an
      inhibitory action on polymorphonuclear neutrophil activities. In the present
      study the potential effect of omeprazole on human natural killer cell (NK)
      activity was investigated. 2. Omeprazole decreased NK cytotoxic activity in a
      dose-dependent manner. 3. Degraded omeprazole showed a similar action. 4. In
      vitro NK inhibitory action of omeprazole and its acid-degraded form was observed
      at the concentrations equal and higher than 18 microM (micromolar). 5. NK
      inhibitory action of omeprazole was recovered to 75% by washing away of the
      agent. 6. Omeprazole decreased the conjugate formation of effector and target
      cells by 50% at the concentration of 288 microM

PMID- 7590141
TI  - Effects of VA-045 on peripheral and central circulation in anesthetized dogs.
AB  - 1. The effects of VA-045, a novel apovincaminic acid derivative, vinpocetine,
      apovincaminic acid, brovincamine and nicergoline on peripheral and cerebral
      circulation were examined in anesthetized dogs. 2. Peripheral circulation: VA-045
      induced a transient decrease in both blood pressure (BP) and heart rate (HR) andd
      an increase in vertebral arterial blood flow (VBF) without affecting femoral
      arterial blood flow (FBF) or carotid arterial blood flow (CBF). Vinpocetine had
      no effect on BP, HR, VBF, FBF or CBF. Apovincaminic acid decreased HR and
      increased VBF without affecting FBF, CBF or BP. Brovincamine increased VBF and
      decreased CBF without affecting BP or FBF. Nicergoline decrease BP without
      affecting VBF, FBA or CBF. 3. Cerebral circulation: VA-045 increased cerebral
      blood flow (CerBF) without affecting BP. Brovincamine also increased CerBF and
      decreased BP. The potency of VA-045 in increasing CerBF was stronger than that of
      brovincamine. Vinpocetine and apovincaminic acid had no effect on BP or CerBF.
      Nicergoline decreased BP but did not affect CerBF. 4. These findings indicate
      that VA-045 has a more selective vasodilative effect on the vertebral and
      cerebral arteries than the other reference drugs.

PMID- 7590142
TI  - Alterations in fluorinated ether anesthetics effects on heme metabolism following
      chronic ethanol consumption.
AB  - 1. The effect of enflurane or isoflurane anesthesia (1 ml/kg, i.p.) in animals
      chronically treated with ethanol (30%, v/v, in drinking water during a week) on
      heme metabolism and its regulation was investigated. 2. In those animals
      previously intoxicated with ethanol that received isoflurane, ALA-S activity was
      increased (control values: 0.071 +/- 0.022 nmol/mg, n = 10; treated animals:
      0.110 +/- 0.034 nmol/mg, n = 8) and blood PBGase and deaminase were strikingly
      diminished (control values, n = 10: PBGase: 0.101 +/- 0.015 nmol/mg, deaminase:
      0.242 +/- 0.075 nmol/mg; treated animals, n = 6: PBGase: 0.063 +/- 0.013 nmol/mg;
      deaminase: 0.145 +/- 0.045 nmol/mg). 3. The time-response study showed that liver
      ALA-S is enhanced at shorter times of anesthesia with isoflurane and that blood
      PBGase and deaminase appeared inhibited later in animals previously treated with
      ethanol. 4. Results reproduce some biochemical alterations known to occur in
      acute intermittent porphyria.

PMID- 7590143
TI  - Effects of piperazine derivatives on the activity of frog skeletal muscle fibers.
AB  - 1. This study was undertaken to characterize the effects of some piperazine
      derivatives on excitable cell membranes. Three original Bulgarian compounds with
      favorable effects on cardiovascular and nervous system--piperazine derivatives
      with code names P-11 (N1-[3-oxo-3-phenyl-2-methyl-propyl]-N4-[trans-3-hydroxy
      1,2,3,4- tetrahydro-2-naphthyl]-piperazine dihydrochloride), AS2 (N1-benzhydryl
      N4-allyl piperazine dihydrochloride) and 35-M (Schiff's base of N1-benzhydryl-N4
      aminopiperazine with triacetonamine, dioxalate salt) were tested in experiments
      with conventional microelectrode technique on isolated frog muscle fibers. 2.
      After 30-min treatment with tested drugs at concentrations of 10-100 microM the
      recorded intra-(ICAP) and extracellular action potentials (ECAPs) showed an
      amplitude decrease and duration increase. The total ionic current (Ii) decreased
      as the outward phase was almost abolished by P-11. The propagation velocity (PV)
      of excitation and the twitch amplitude also decreased. These changes were agent-
      and concentration-dependent. 3. The effect potency of the agents diminished in
      the following order: P-11 > AS2 > 35-M. 4. Concentrations higher than 100 microM
      for all agents completely, but reversibly, inhibited membrane excitability. 5.
      The results demonstrate compound- and concentration-induced modulation of Ca2+
      current with blockade of Ca(2+)-dependent K+ and Cl- membrane channels of muscle
      fiber treated with the compound tested.

PMID- 7590144
TI  - We must not let third parties influence treatment rendered.

PMID- 7590145
TI  - Dental treatment for family members.

PMID- 7590146
TI  - The top 20 medications prescribed in 1993.

PMID- 7590147
TI  - Uses of chlorhexidine in dentistry.

PMID- 7590148
TI  - Secondary caries: relation with current criteria used to replace restorations.

PMID- 7590149
TI  - Effect of bleaching on microhardness, morphology, and color of enamel.

PMID- 7590151
TI  - Dental practice patterns. II: Treatment related to oral health status.

PMID- 7590150
TI  - Dentists' knowledge, attitudes, and assessment practices in relation to fearful
      dental patients: a pilot study.

PMID- 7590152
TI  - Laboratory testing of light-cured glass ionomers as pit and fissure sealants.

PMID- 7590154
TI  - Agglutination of Staphylococcus saprophyticus: a structural and cytochemical
      study.
AB  - Staphylococcus saprophyticus was shown to be agglutinated by wheat germ
      agglutinin, wheat germ agglutinin-biotin and bovine serum albumin-p-aminophenyl-N
      acetyl-beta-D-glucosaminide (GlcNAc-BSA), and sheep red blood cells. In these
      agglutinations, filamentous or amorphous structures radiating from the surface of
      S. saprophyticus were demonstrated by electron microscope observation.
      Cytochemical analyses of the agglutination revealed the binding sites of wheat
      germ agglutinin in S. saprophyticus and the binding sites of GlcNAc in the sheep
      red blood cells and S. saprophyticus. Since GlcNAc-BSA contains N
      acetylglucosamine to which wheat germ agglutinin can bind, it is most likely that
      an interaction between a wheat germ agglutinin-bindable substance in S.
      saprophyticus and an N-acetylglucosamine-bindable substance in sheep red blood
      cells is involved in the agglutination.

PMID- 7590153
TI  - Clinical evaluation of buffered local anesthetic.

PMID- 7590156
TI  - Staphylococcus pasteuri-specific oligonucleotide probes derived from a random
      amplified DNA fragment.
AB  - A rapid polymerase chain reaction method was developed to differentiate
      Staphylococcus pasteuri from other staphylococcal species, especially the
      phenotypically similar S. warneri. The oligonucleotide probes used as primers
      were designed from the sequence of a S. pasteuri random amplified polymorphic DNA
      fragment.

PMID- 7590155
TI  - Induction of vancomycin resistance in Enterococcus faecium by non-glycopeptide
      antibiotics.
AB  - Bacitracin and other antibiotics that inhibit late stages in peptidoglycan
      biosynthesis induce vancomycin resistance in a high-level, inducibly vancomycin
      resistant strain of Enterococcus faecium. Exposure to bacitracin led to synthesis
      of the lactate-containing UDP-MurNAc-pentadepsipeptide precursor required for
      vancomycin resistance. These findings indicate that inhibition of peptidoglycan
      biosynthesis can lead to induction of vancomycin resistance and raise the
      possibility that multiple signals may serve to induce resistance.

PMID- 7590159
TI  - Rapid identification of Streptococcus pneumoniae by PCR amplification of
      ribosomal DNA spacer region.
AB  - Streptococcus pneumoniae is one of the important human pathogens in clinical
      microbiology. A polymerase chain reaction assay was designed to detect and
      identify S. pneumoniae through amplification of the ribosomal DNA spacer regions
      between the pneumococcal 16S-23S ribosomal RNA genes. Thirty-two Streptococcus
      and non-Streptococcus strains were tested to verify the specificity of the assay,
      and only S. pneumoniae strains gave a positive reaction. This method is a
      powerful technique for the rapid identification of S. pneumoniae.

PMID- 7590158
TI  - Effects of glucose, tetrapyrroles and protein kinase C activators on cell
      proliferation in cultures of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae was inoculated into a yeast nitrogen base with either
      glycerol or glucose as carbon source. Cell proliferation was followed by colony
      counts on agar medium. Cells in the glycerol-supplemented medium divided less
      than once in 10 days. When glucose, 6-deoxy-glucose or protoporphyrin IX was
      added, the cells had doubling times of about 24 h and increased in number to
      about 0.5 x 10(6) cells ml-1. Addition of either of the protein kinase C
      activators oleoyl-acetyl-glycerol or phorbol-12-myristate-13-acetate did not
      activate cell proliferation in the glycerol medium. However, when (i) glucose was
      combined with either protoporphyrin IX or chlorophyllin, or (ii) either
      protoporphyrin IX or chlorophyllin was combined with either of the protein kinase
      C activators, the cells had doubling times of about 12 h. Hence, (i) glucose can
      act as both a carbon source and a signalling molecule for proliferation, and (ii)
      two systems are involved in activating cell proliferation in S. cerevisiae: one
      operating through a protein kinase C system and another through a guanylate
      cyclase system.

PMID- 7590160
TI  - Enteroaggregative strains of Escherichia coli belonging to serotypes O126:H27 and
      O44:H18 express antigenically similar 18 kDa outer membrane-associated proteins.
AB  - Outer membrane-associated proteins of 18 kDa were expressed by enteroaggregative
      Escherichia coli (EAggEC) belonging to serotypes O126:H27 and O44:H18, which
      hybridized with a probe derived from a plasmid necessary for enteroaggregative
      adhesion. The 18 kDa proteins expressed by strains of E. coli, belonging to these
      serotypes, were surface exposed and antigenically similar but not structurally
      identical.

PMID- 7590157
TI  - An additional PII in Escherichia coli: a new regulatory protein in the glutamine
      synthetase cascade.
AB  - The PII protein in the glutamine synthetase cascade transduces the nitrogen
      signal, as sensed by uridylyltransferase, both to the NRII/NRI two-component
      system and to adenylyltransferase, to regulate the activity of glutamine
      synthetase. Here we describe the amplification of a chromosomal DNA fragment from
      Escherichia coli which contains the sequence of a PII homologue. The derived
      amino acid sequence of this DNA fragment is 67% identical to E. coli PII. It
      contains the conserved tyrosine residue which is known to be the site of
      uridylylation in PII. E. coli is the first organism in which two different PII
      proteins have been detected.

PMID- 7590161
TI  - The actin-polymerization protein from Listeria ivanovii is a large repeat protein
      which shows only limited amino acid sequence homology to ActA from Listeria
      monocytogenes.

PMID- 7590163
TI  - Post-transcriptional control and kinetic characterization of proline transport in
      germinating conidiospores of Aspergillus nidulans.
AB  - In the filamentous fungus Aspergillus nidulans, L-proline uptake is mediated by
      the product of the prnB gene which codes for a member of a family of amino acid
      transporters found both in pro- and eukaryotes. Regulation of prnB gene
      expression has previously been studied in great detail at the molecular level.
      However, no studies have addressed possible post-transcriptional controls or the
      kinetic characterisation of the PrnB transporter. Here we develop a rapid and
      efficient method for direct uptake measurements of proline in germinating
      conidiospores of A. nidulans. We make use of this method and Northern blot
      analyses in parallel to study the regulation of PrnB expression both at the level
      of prnB message accumulation and at a post-transcriptional level. These studies
      show that (i) pathway-specific and wide-domain regulatory systems, previously
      shown to control prnB gene expression in multicellular mycelia, also operate in
      unicellular conidia committed to germination; and (ii) PrnB activity is regulated
      in response to the nitrogen source present in the medium and the level of
      internally accumulated proline or other amino acids. We also characterise
      kinetically the PrnB transporter and a secondary proline transport system. Our
      results open new possibilities for studies using unicellular conidiospores of
      filamentous fungi and constitute a necessary first step for a subsequent
      structure-function analysis of the PrnB transporter.

PMID- 7590164
TI  - A hydroxymethylglutaryl-CoA reductase inhibitor synthesized by yeasts.
AB  - Screening of different yeast species showed that they are able to synthesize
      hydroxymethylglutaryl-CoA (HMGCoA) reductase inhibitors. Crude methanol extracts
      and the purified inhibitors from Pichia labacensis and Candida cariosilignicola
      were tested for their biological activity on the solubilized microsomal HMGCoA
      reductase from Chinese hamster ovary cells. Identification of the inhibitors was
      studied by thin layer chromatography, high pressure liquid chromatography and
      mass spectroscopy.

PMID- 7590162
TI  - Construction of an integrative shuttle vector for Zymomonas mobilis.
AB  - An integrative shuttle vector, pZMOCP1, was constructed by ligating EcoRV digests
      of the plasmid cloning vector pBluescript and pZMP1, a cryptic plasmid of
      Zymomonas mobilis PROIMI A1. The 7.2-kb plasmid pZMOCP1 replicated in Escherichia
      coli and could also be transferred from this host by electroporation to Z.
      mobilis ATCC 29191. The transformants were selected by ampicillin resistance. The
      integrative characteristic was detected by hybridization in situ. The vector was
      stably maintained in Z. mobilis after 200 generations without selective pressure.

PMID- 7590165
TI  - A novel gyrB mutation in a fluoroquinolone-resistant clinical isolate of
      Salmonella typhimurium.
AB  - In order to study the role of gyrB in antibiotic resistance in post-ciprofloxacin
      therapy fluoroquinolone-resistant clinical isolates of Salmonella typhimurium,
      plasmid pBP548, which contains the Escherichia coli gyrB gene, was used in
      complementation studies. In a heterodiploid strain, the wild-type (quinolone
      sensitive) allele is dominant over the resistant allele therefore, eleven
      clinical isolates were complemented with gyrB encoded on pBP548. Only one
      transformant, L18pBP548, exhibited increased susceptibility to the quinolones
      nalidixic acid, ciprofloxacin and sparfloxacin. The amino acid sequence of the
      gyrase B protein from a wild-type and the pre-therapy S. typhimurium (deduced
      from the nucleotide sequence) was identical to that of E. coli from codons 436 to
      470; however, a point mutation was identified in codon 463 of gyrB of the
      quinolone-resistant post-therapy isolate L18, giving rise to an amino acid
      substitution of serine to tyrosine.

PMID- 7590166
TI  - Bleomycin-induced beta-lactamase overexpression in Escherichia coli carrying a
      bleomycin-resistance gene from Streptomyces verticillus and its application to
      screen bleomycin analogues.
AB  - A bleomycin-resistance gene, designated blmA, has been cloned from bleomycin
      producing Streptomyces verticillus by Sugiyama et al. (Gene 151 (1994) 11-16).
      The present study shows that Escherichia coli harboring the blmA-carrying pUC
      plasmid overproduced beta-lactamase, encoded by an ampicillin-resistance gene on
      the plasmid, when cultured in the presence of bleomycin, which suggests that
      bleomycin may act as an inducer (or an activator) for the expression of the
      specific gene in the presence of blmA. We constructed a vector, designated
      pMAB50, which senses bleomycin and produces a pigment, using blmA and a
      Streptomyces tyrosinase gene located under the control of beta-lactamase
      promoter: E. coli harboring pMAB50 produced the melanin pigment in the presence
      of bleomycin-type antibiotics, suggesting that the transformed E. coli can be
      employed as a reporter organism to screen bleomycin analogues.

PMID- 7590169
TI  - High-molecular-mass, iron-repressed cytoplasmic proteins in fluorescent
      Pseudomonas: potential peptide-synthetases for pyoverdine biosynthesis.
AB  - High molecular-mass cytoplasmic proteins were detected in iron-starved,
      pyoverdine-producing Pseudomonas aeruginosa, P. chlororaphis, P. fluorescens, P.
      putida, P. aptata and P. tolaasii. They appeared to be specifically located in
      the cytoplasm and thus were termed 'IRCPs', for iron-repressed cytoplasmic
      proteins. A strain-dependent gel electrophoresis pattern with multiple bands of
      M(r) values ranging from 180 to 600 kDa was usually observed for these proteins.
      Strains synthesizing pyoverdines differing in their peptide part presented
      different IRCP gel electrophoresis profiles, whereas strains synthesizing
      identical pyoverdines had identical IRCP gel electrophoresis profiles. Some
      mutants affected in pyoverdine biosynthesis presented a perturbed IRCP pattern,
      and no IRCPs were detected in non-fluorescent Pseudomonas strains either unable
      to synthesize siderophores or synthesizing non-peptidic siderophores. The data
      strongly suggest that the IRCPs could be related to peptide synthetases involved
      in the biosynthesis of the peptidic part of pyoverdine-type siderophores.

PMID- 7590167
TI  - Fts insertional mutant of Salmonella typhimurium.
AB  - A temperature-sensitive filamentation (fts) Salmonella typhimurium mutant was
      isolated after transposon mutagenesis with mini-Tn 10dTc. The mutant was unable
      to form colonies after 20 h incubation at 37 degrees C on LB agar. Colonies
      appeared, however, after longer incubation at the restrictive temperature.
      Filamentation affected only part of the bacterial population. Rapid mapping using
      Mu dP22 hybrid phages revealed that the mutation, ftsD220, lies within minutes
      68.5 and 73.6 on the genetic map. Further analysis revealed that the ftsD220
      mapped at min 73 and that it is linked to cysG (6%) and to aroB (39%).
      Complementation tests suggested that the ftsD220 mutation is not homologous to a
      Escherichia coli ftsH mutation.

PMID- 7590168
TI  - Evidence for a defective prophage on the chromosome of Methanobacterium wolfei.
AB  - Evidence shows the presence on the chromosome of Methanobacterium wolfei of a
      defective prophage which, by DNA-DNA hybridization, is closely related to the
      virulent archaeophage psi M1 of Methanobacterium thermoautotrophicum Marburg.
      Partial sequencing of a M. wolfei 16S rRNA gene and phylogenetic analysis
      indicated that this organism is more closely related to other representatives of
      the genus Methanobacterium than to M. thermoautotrophicum Marburg. The
      chromosomal region of M. wolfei encoding the putative prophage was found to be
      deleted for two non-contiguous segments of the phage psi M1 genome and thus
      encompassed only 80 to 90% of the psi M1 DNA. The prophage region was mapped to a
      30 kb restriction fragment on the physical map of the M. wolfei chromosome. A
      randomly chosen DNA fragment was cloned from phage psi M1 DNA, as was its
      homologous counterpart from the chromosome of M. wolfei. The 126-bp region
      present in both clones exhibited 100% sequence identity.

PMID- 7590170
TI  - Phylogenetic position of the menaquinone-containing acidophilic chemo-organotroph
      Acidobacterium capsulatum.
AB  - The phylogenetic position of an acidophilic chemo-organotrophic menaquinone
      containing bacterium, Acidobacterium capsulatum, was studied on the basis of 16S
      rRNA gene sequence information. A. capsulatum showed the highest level of
      sequence similarity to Heliobacterium chlorum, a member of the Gram-positive
      group, yet this level was only 81%. Distance matrix tree analysis suggested that
      A. capsulatum belongs to a unique lineage deeply branching from the Chlamydia
      Planctomyces group or from the Gram-positive line.

PMID- 7590171
TI  - Invasion of HeLa cells by Mycoplasma penetrans and the induction of tyrosine
      phosphorylation of a 145-kDa host cell protein.
AB  - The ability of Mycoplasma penetrans to invade eukaryotic cells was studied using
      a HeLa cell line. The bactericidal antibiotic, gentamicin, in combination with
      low concentrations of Triton X-100, was utilized to kill mycoplasmas that had not
      entered the cells, allowing the quantitation of internalized organisms. The
      intracellular location of the mycoplasma was also documented by transmission
      electron microscopy. The actin polymerization inhibitor cytochalasin-D markedly
      inhibited the internalization process, whereas the tyrosine phosphorylation
      inhibitors, staurosporin and genistein had only a slight effect. As against the
      invasion of enteropathogenic Escherichia coli which depends on tyrosine
      phosphorylation of a 90-kDa (Hp90) HeLa cell protein, internalization of M.
      penetrans by HeLa cells was independent of the phosphorylation of Hp90.
      Nonetheless, tyrosine phosphorylation of a 145-kDa HeLa cell protein was found to
      be associated with the interaction of M. penetrans with HeLa cells.

PMID- 7590172
TI  - Characterisation of ovine Bordetella parapertussis isolates by analysis of
      specific endotoxin (lipopolysaccharide) epitopes, filamentous haemagglutinin
      production, cellular fatty acid composition and antibiotic sensitivity.
AB  - Isolates of Bordetella parapertussis, recovered from sheep or man, were
      characterised by reaction with specific anti-Bordetella lipopolysaccharide
      monoclonal antibodies, production of filamentous haemagglutinin, fatty acid
      patterns, and antibiotic sensitivity. Generally, the isolates lay within one of
      four groups, with separation of the ovine isolates into two groups. Reactions
      with specific monoclonal antibodies against lipopolysaccharide separated the
      ovine isolates into these two groupings. Analysis of the cellular fatty acid
      compositions by cluster analysis differentiated between the human and the ovine
      strains and also showed variation within the ovine isolates. When the production
      of filamentous haemagglutinin was analysed in an ELISA system, a similar pattern
      emerged. Varying concentrations of filamentous haemagglutinin (11-429 ng (mg
      total protein)-1) were extracted from the human isolates and the one group of
      ovine isolates with no significant protein detected in the other ovine group.
      These studies demonstrate variation between and within B. parapertussis isolates
      recovered from two mammalian sources.

PMID- 7590173
TI  - Evidence that particulate methane monooxygenase and ammonia monooxygenase may be
      evolutionarily related.
AB  - Genes encoding particulate methane monooxygenase and ammonia monooxygenase share
      high sequence identity. Degenerate oligonucleotide primers were designed, based
      on regions of shared amino acid sequence between the 27-kDa polypeptides, which
      are believed to contain the active sites, of particulate methane monooxygenase
      and ammonia monooxygenase. A 525-bp internal DNA fragment of the genes encoding
      these polypeptides (pmoA and amoA) from a variety of methanotrophic and
      nitrifying bacteria was amplified by PCR, cloned and sequenced. Representatives
      of each of the phylogenetic groups of both methanotrophs (alpha- and gamma
      Proteobacteria) and ammonia-oxidizing nitrifying bacteria (beta- and gamma
      Proteobacteria) were included. Analysis of the predicted amino acid sequences of
      these genes revealed strong conservation of both primary and secondary structure.
      Nitrosococcus oceanus AmoA showed higher identity to PmoA sequences from other
      members of the gamma-Proteobacteria than to AmoA sequences. These results suggest
      that the particulate methane monooxygenase and ammonia monooxygenase are
      evolutionarily related enzymes despite their different physiological roles in
      these bacteria.

PMID- 7590174
TI  - High level expression of Streptococcus pyogenes erythrogenic toxin A (SPE A) in
      Escherichia coli and its rapid purification by HPLC.
AB  - The speA gene encoding streptococcal erythrogenic toxin A (SPE A) from
      Streptococcus pyogenes bacteriophage T12 was overexpressed in Escherichia coli
      under the control of the T7 promoter. Since most of the expressed protein was
      found in the periplasmic space, an osmotic shock extraction with 0.5 M sucrose
      resulted in a highly enriched preparation of SPE A. An additional two-step
      purification employing high pressure liquid chromatography resulted in a purified
      SPE A protein.

PMID- 7590175
TI  - The aniline blue fluorochrome specifically stains the septum of both live and
      fixed Schizosaccharomyces pombe cells.
AB  - A novel method is described which uses aniline blue for the specific fluorescent
      staining of the septa of dividing cells of the fission yeast, Schizosaccharomyces
      pombe. It gives the same results with live and fixed cells. In fixed or, more
      generally, dead cells there is no staining of the cytoplasm: this renders aniline
      blue superior to other dyes previously used to stain the septum of S. pombe. This
      feature allows quantitative analysis of the septum index for fixed samples and,
      therefore, makes aniline blue the stain of choice for cell cycle kinetic studies.

PMID- 7590178
TI  - High sensitivity of Mycobacterium species to the bactericidal activity by
      polylysine.
AB  - Bactericidal effects of polylysine on different bacterial species were measured.
      Marked differences in sensitivity were observed. Based on the concentration of
      polylysine required to reduce cell viability by 50%, Mycobacterium smegmatis and
      Mycobacterium tuberculosis were found to be the most sensitive and Escherichia
      coli the most resistant. In addition, two Gram-positive organisms, Staphylococcus
      epidermidis and Streptococcus salivarius exhibited significant differences in
      sensitivity which suggests that the relationship between sensitivity towards
      polylysine and bacterial cell type is not necessarily a function of the overall
      cell envelope structure. The high sensitivity of mycobacteria suggests the
      possible use of polylysine, or a conjugate of polylysine and another agent in
      anti-mycobacterial drug design.

PMID- 7590176
TI  - FemA of Staphylococcus aureus: isolation and immunodetection.
AB  - FemA, a cytoplasmic protein necessary for the expression of methicillin
      resistance in Staphylococcus aureus and also involved in the biosynthesis of
      staphylococcal cell walls, was detected and quantified in several S. aureus
      strains under different growth conditions by Western immunoblot. Two types of
      antigens were used for the production of polyclonal antibodies against FemA: (i)
      a synthetic peptide comprising 14 amino acids of its C-terminal sequence; and
      (ii) FemA isolated by preparative gel electrophoresis and electroelution from an
      overproducing staphylococcal strain. Immunodetection revealed that all
      investigated strains, either methicillin-resistant or susceptible, expressed FemA
      during the exponential growth phase in varying amounts. In the stationary phase,
      the FemA content was diminished. Strains in which femA was inactivated by
      insertion of Tn551 into the control region of the femAB operon still expressed
      about 10% of the protein compared to their parent strains. Tn551 insertion in the
      middle of the femB gene did not affect the FemA expression. In 40 methicillin
      susceptible and 6 resistant clinical isolates of S. aureus, the FemA content or
      its affinity to the antibodies was reduced compared to laboratory parent strains.
      In susceptible strains, an additional protein of higher molecular weight, present
      in large quantities, was also able to bind the FemA antibodies. Such a protein
      was also present in methicillin-resistant isolates, although it was not as
      pronounced as in the susceptible strains.

PMID- 7590177
TI  - Nitrogen-source-induced activation of neutral trehalase in Schizosaccharomyces
      pombe and Pachysolen tannophilus: role of cAMP as second messenger.
AB  - Resting cells of the fission yeast Schizosaccharomyces pombe, suspended in buffer
      with glucose, responded to the addition of asparagine by increasing trehalase
      activity. This response was preceded by a peak in cAMP concentration. The
      addition of the nitrogen source to resting cells, devoid of the catalytic subunit
      of cAMP-dependent protein kinase, produced the transient increase in cAMP but did
      not promote any change in trehalase activity. In the budding yeast Pachysolen
      tannophilus, the activation of trehalase by nitrogen source was also accompanied
      by a sharp peak in cAMP. These results suggest that in the two yeasts cAMP acts
      as a second messenger in the transduction of the nitrogen-source-induced signal
      causing the activation of trehalase.

PMID- 7590179
TI  - Genome map of Campylobacter fetus subsp. fetus ATCC 27374.
AB  - A physical map of the chromosome of Campylobacter fetus subsp. fetus was
      constructed by using pulsed-field gel electrophoresis of restriction fragments
      generated by SalI, SmaI and NotI. Digestion of the type strain ATCC 27374 with
      these restriction endonucleases resulted in generating 4-14 fragments. The order
      of the fragments was deduced from hybridization of these restriction fragments to
      Southern blots of pulsed-field gel electrophoresis gels generated by the other
      two enzymes. The estimated genome size was 1160 kb. The position of several
      homologous and heterologous genes was determined on the circular map. These
      included the 2.8-kb sapA gene, encoding the 97-kDa surface array protein. Three
      copies of ribosomal RNA genes for which the 16S, 23S and 5S rRNA appeared to be
      located in close proximity in each of the three regions. The RNA polymerase genes
      rpoA, rpoB, and rpoD were mapped and appeared to be situated close together in
      one region. The flagellin genes (flaAB) of C. jejuni and the gyrase genes gyrA
      and gyrB of C. perfringens and Bacillus subtilis, respectively, were used to
      identify the locations of flaAB, the gyrA and the gyrB genes on the ATCC 27374
      chromosome.

PMID- 7590180
TI  - Pili of Pasteurella multocida of porcine origin.
AB  - Using electron microscopy, pili with at least two distinct morphologies were
      observed on strains of Pasteurella multocida isolated from pigs with atrophic
      rhinitis. Rigid pili were found on 60-80% of all cells observed. These pili had a
      strong tendency to lie flat along the side of the outer cell membrane of P.
      multocida and as a result frequently were difficult to see. After growth in
      vitro, piliated P. multocida cells produced few pili (approx. 3-5 per cell).
      Heavily piliated cells were occasionally observed. The second type of pili were
      curly and also were difficult to visualize. Cells from cultures containing
      piliated cells failed to attach to red blood cells and to immobilized mucus.

PMID- 7590181
TI  - Ultrastructural effects of pressure stress to the nucleus in Saccharomyces
      cerevisiae: a study by immunoelectron microscopy using frozen thin sections.
AB  - The effects of hydrostatic pressure on subcellular structures, particularly the
      nucleus, of Saccharomyces cerevisiae were investigated by immunoelectron
      microscopy. Cells were treated with hydrostatic pressure from 0.1 to 400 MPa for
      10 min at room temperature. Frozen thin sections of the cells revealed that
      spindle pole bodies disappeared at 100 MPa. At 150 MPa, the deposition of gold
      particles for anti alpha-tubulin was noticed in the nucleus, although the
      filamentous structure of microtubules was lost. At 200 MPa, fewer gold particles
      were scattered in the nucleus and the nuclear membrane in several portions was
      also observed to be open at 300 MPa. These results show that elements of the
      nuclear division apparatus were susceptible to pressure stress, particularly
      spindle pole bodies and microtubules. The damage to spindle pole bodies,
      microtubules, and nuclear membrane caused by pressure stress was followed by the
      inhibition of nuclear division. After the release of pressure, the spindle pole
      bodies and microtubules of pressurized cells at below 200 MPa regained their
      normal appearance at 24 h.

PMID- 7590182
TI  - Membrane hyperpolarisation by valinomycin and its limitations for bacterial
      viability assessment using rhodamine 123 and flow cytometry.
AB  - The ionophore, valinomycin, was investigated as a possible means of bacterial
      viability assessment using the fluorescent membrane potential dye rhodamine 123.
      Membrane hyperpolarisation in Escherichia coli, Pseudomonas fluorescens,
      Enterobacter aerogenes and Arthrobacter globiformis was examined during
      exponential growth and during stress by brief starvation in a high sodium, low
      potassium buffer using flow cytometric analysis of rhodamine 123 uptake. Dye
      uptake was variable both between species and amongst cells from the same culture.
      Exponential phase cells showed no increase in dye uptake due to valinomycin
      treatment. Stressed P. fluorescens cells responded to valinomycin treatment by
      increased dye uptake, while stressed E. coli and A. globiformis cells showed no
      response. Approximately 50% of stressed Eb. aerogenes cells responded to
      valinomycin. The results demonstrate the limitations of rhodamine dye for
      viability analysing the viability of diverse bacterial communities and underline
      the degree of cell heterogeneity in batch cultures.

PMID- 7590184
TI  - Heavy metal effects on Proteus mirabilis superoxide dismutase production.
AB  - Proteus mirabilis expressed three superoxide dismutase activities, which depended
      on the level of soluble iron and dioxygen in the culture medium. Cadmium and lead
      decreased production of super oxide dismutase in liquid culture and on solid
      medium. A fourth super oxide dismutase activity appeared in extracts from cells
      grown in the presence of cadmium. These results support the idea of an
      interaction between toxic metal ions and putative iron- and redox-dependent
      regulatory systems.

PMID- 7590183
TI  - Local comparison of the genomes of Mycobacterium tuberculosis and Mycobacterium
      leprae using the polymerase chain reaction.
AB  - To facilitate comparison of the genome maps of Mycobacterium tuberculosis and M.
      leprae, sequence data from the M. leprae sequencing project were used to design
      primers suitable for the amplification of short segments from conserved genes by
      the polymerase chain reaction. In most cases, both organisms yielded products of
      identical size that were then used as probes for a comparative genomic walk. The
      hybridization data often, but not always, revealed a similar organization of
      various regions of both genomes. This approach should be useful for systematic
      comparisons of (myco)bacterial genomes.

PMID- 7590185
TI  - Variable sequences in a mosaic-like domain of meningococcal tbp2 encode
      immunoreactive epitopes.
AB  - Transferrin-binding proteins from Neisseria meningitidis vary among different
      isolates. We have identified and studied a hypervariable region adjacent to the
      carboxyl-end of the transferrin-binding domain of the Tbp2 molecule. The tbp2
      genes from six strains of N. meningitidis were cloned and sequenced in this
      particular region. Sequence analysis of these regions along with five other
      sequences available from pathogenic Neisseria showed a common organisation of
      seven highly variable nucleotide stretches interspersed with six conserved
      nucleotide stretches. The variable regions correlated with the location of
      immunoreactive epitopes in polyclonal antisera raised to transferrin-binding
      proteins identified by peptide pin technology. Sequence analysis suggested a
      mosaic-like organisation of the tbp2 genes. Taken together, these data suggest
      that the antigenic variation in this part of the protein may result from a strong
      host immune pressure.

PMID- 7590186
TI  - Managed care: a catalyst for integrated medicine.

PMID- 7590187
TI  - General hospital psychiatry and the new behavioral health care delivery system.
AB  - Mental health care delivery has undergone substantial changes in recent years.
      This article reviews the evolution of managed care in the mental health care
      field and outlines managed behavioral health care techniques used in providing
      access to high-quality, cost-effective care. The expansion of general hospital
      psychiatry over the last 25 years is also reviewed. Current strengths of general
      hospital psychiatry which make it well positioned for an expanded role in
      behavioral health care delivery are examined. Recommendations are made for
      further improvements in the clinical, administrative, and financial aspects of
      general hospital psychiatry care delivery to prepare it for the integrated
      behavioral health care systems of tomorrow.

PMID- 7590189
TI  - The continuum of care in a general hospital setting.
AB  - Service delivery in behavioral health is shifting from the traditional two-tiered
      model of care that has favored inpatient and outpatient treatment. In its place,
      a new paradigm based upon a broad and fluid continuum of services is now becoming
      recognized for its contributions to quality of care and efficiency in
      contemporary system design. This article provides an overview of the forces that
      have stimulated the development of continuum-based programs and services. The
      characteristics of an effective continuum are discussed as well as barriers that
      impede its development. Finally, the evolving levels of care within the continuum
      are addressed and an integrated continuum model is presented.

PMID- 7590188
TI  - Wagons ho: forward on the managed care trail.
AB  - This paper describes the impact of managed care on an academic medical center
      department of psychiatry. Like the pioneers before us, academic medical centers
      have often traveled wilderness paths, training new generations of psychiatrists
      and providing research about and new understandings of psychiatric illness; under
      assault from powerful competitive forces, we have all too often circled the
      wagons in an attempt to survive what we perceive as an onslaught. We describe the
      ways in which our academic medical center department of psychiatry has responded
      to managed care forces, in particular, the impact of managed care on residency
      training, inpatient services, outpatient psychotherapeutic and
      psychopharmacological care, and faculty morale. We describe how we have worked
      closely with our medical colleagues, formed new committees, and initiated forays
      into capitated arrangements. Despite difficult external circumstances, we have
      been able to survive, regroup, provide leadership, and continue with renewed
      purpose.

PMID- 7590191
TI  - Initiating a capitated program for HMO patients.
AB  - In 1986, our hospitals were selected by a large Massachusetts independent
      practice HMO to administer a capitated program for psychiatric inpatients
      residing in Boston and in neighboring northern cities and towns. Administering
      this program necessitated designing new systems of accounting, utilization
      review, physician reimbursement, staff education, orientation, and management
      control as well as contracting with other hospitals for locked psychiatric beds.
      It also included developing day treatment, crisis intervention, and visiting
      nurse services. Psychiatrists had to adapt to a new reimbursement system which
      paid by the admission or which withheld 30% of payment until program performance
      was evaluated. Those who valued intrapsychic change found it hard to value crisis
      intervention and symptom reduction to the same degree. Although there was
      considerable variation in each hospital's performance, there was over a 25%
      decrease in patient days and an overall reduction in readmission rate during the
      first year of the program.

PMID- 7590192
TI  - The effect of managed care on the treatment outcome of substance use disorders.
AB  - This study examined the effect of managed care and other reimbursement mechanisms
      on the outcome of substance abuse treatment at a single treatment facility. A
      retrospective review of 1594 patient records yielded treatment utilization,
      diagnostic, and demographic data. Recidivism rates for intensive managed care,
      traditional managed care, private pay, and state-funded groups of patients were
      compared. Results showed that, contrary to expectations, recidivism rates were
      not different for managed vs nonmanaged care patients. In addition, recidivist
      patients had significantly more ICD-9 diagnoses than nonrecidivist patients. A
      discussion of future research suggests that other outcome measures need to be
      examined in addition to recidivism rate, such as psychosocial functioning
      following treatment and indicator(s) of severity of illness, to better determine
      the effect of managed care and other reimbursement mechanisms on treatment
      outcome.

PMID- 7590190
TI  - The future of consultation-liaison psychiatry and medical-psychiatric units in
      the era of managed care.
AB  - There has been increasing recognition and documentation of the impact of
      psychiatric problems on the outcome and cost of medical care. Because
      consultation-liaison psychiatrists have the expertise to address the psychiatric
      aspects of medical illness, this group should be in a strong position to
      facilitate integration of medical and psychiatric services in managed care
      delivery systems. Although consultation-liaison psychiatry (CLP) has documented
      its ability to shorten inpatient medical lengths of stay for some disorders, a
      greater challenge exists in developing comprehensive systems to identify and care
      for patients with mental health problems in primary care settings. This paper
      reviews the fiscal and programmatic implications for managed medical care systems
      of findings from outcome-based C-L research. The future role of CLP and combined
      medical-psychiatric units in an era of managed care is also discussed.

PMID- 7590193
TI  - General hospital psychiatry and the ethics of managed care.
AB  - Managed care programs come in many stripes, and the field is evolving with
      bewildering rapidity. In order to be effective advocates and critics, clinicians
      need a vision of ethical managed care practice, to use as a standard for judgment
      and quality improvement. This paper presents four principles that I believe
      capture the essential stance of an ethical clinician in managed care. The central
      challenge for creating ethical managed care systems is integrating stewardship
      (communitarian) and fiduciary (patient centered) values. Because general hospital
      psychiatrists treat individual patients in a "communal" (institutional) setting
      in which issues of resource use stand out with great clarity, they will play a
      central role in developing ethical guidelines for managed care practice. This
      paper considers issues in general hospital psychiatric practice--determining
      hospital length of stay, deciding how much suicidal risk is tolerable in a
      treatment plan, and the problems that arise when patients prefer valid but less
      cost-effective treatments--as examples of the kinds of questions a clinically
      relevant set of ethics must address.

PMID- 7590196
TI  - A rare case of self-mutilation: self-enucleation of both eyes.

PMID- 7590194
TI  - Affective disorders, social support, and health status in geriatric patients in a
      general hospital.
AB  - A randomized-sample taken from all elderly patients aged 70 years and over
      hospitalized for medical/surgical disorders was studied (N = 108) to determine
      the influence of health problems and social support on depression. According to
      DSM-III-R diagnostic criteria, 50.9% had psychiatric disorders and 15.7% had
      affective disorders. In the total sample, depressive symptoms significantly
      correlated with the existence of health problems and lack of social support, but
      independently considered, these variables did not have a significant influence on
      diagnoses of depressive disorders.

PMID- 7590195
TI  - Cognitive change after treatment for neurosyphilis. Correlation with CSF
      laboratory measures.
AB  - The decision to re-treat a patient with neurosyphilis is usually based on the
      clinical response, cerebrospinal fluid (CSF), cell count, and CSF protein
      concentration. The value of the CSF Venereal Disease Research Laboratory (VDRL)
      test on its own as a marker for treatment response in neurosyphilis has not been
      established. To assess the usefulness of CSF markers for continuing infection, 12
      patients with neurosyphilis were reevaluated 1 year after treatment. Change in
      cognitive functioning, as assessed by the Mini-mental State Examination (MMSE),
      was correlated with the CSF cell count, protein content, IgG index, and VDRL test
      titer at follow-up. A significant negative correlation was obtained between 1
      year improvement in MMSE score and CSF VDRL titers at both the 6- and the 12
      month follow-up examinations, and with the 6-month CSF protein concentration.
      These findings suggest that the CSF VDRL titer may be an indicator of continued
      Treponema pallidum activity in patients without obvious clinical deterioration.

PMID- 7590198
TI  - [Inheritability of personality traits measured by MMPI in families of
      schizophrenic patients].
AB  - The results of genetic and mathematical analysis of MMPI-measured personality
      traits performed on material obtained 37 families of schizophrenia-afflicted
      probands were outlined. The results obtained suggest that heritability of traits
      in schizophrenic families is higher than in the general population. The
      discriminant function significantly differentiating between schizophrenics' and
      healthy people's relatives and having high heritability was calculated.

PMID- 7590197
TI  - [Allelic variants of apolipoproteins B and CII genes in patients with ischemic
      heart disease and in healthy persons from the Moscow population].
AB  - Allelic frequencies of a microsatellite of the apolipoprotein CII gene (APOCII)
      and a minisatellite of the apolipoprotein B gene (APOB) were studied using
      polymerase chain reaction (PCR). The study was conducted on a random sample of
      male Moscow inhabitants and a sample of patients with coronary heart disease
      (CHD) from the same population. Fourteen variants of the APOB minisatellite (the
      82% heterozygosity level) and 13 alleles of the APOCII microsatellite (the 85%
      heterozygosity level) were found. CHD patients significantly differed from the
      control group in the distributions of alleles in these loci: APOB 32, APOB 46,
      APOB 48, and APOB 50 as well as APOCII 17 and APOCII 29 were found more
      frequently. A relationship was found between the distributions of APOB and APOCII
      in the CHD patients. The CHD patients with alleles APOCII 21 and APOCII 30 very
      often had the allele APOB 32; and patients with the genotype APOB 34, 36 had the
      allele APOCII 29 even more often than affected individuals in general.
      Individuals of the control group with the allele APOCII 30 exhibited
      hypertriglyceridemia without increased levels of total cholesterol and
      apolipoprotein B in plasma.

PMID- 7590199
TI  - [Mitochondrial introns of fungi and their role in evolution].

PMID- 7590200
TI  - [Genetic study of plasmid pVM82 which contributes to the pathogenicity of the
      pseudotuberculosis pathogen].
AB  - The large pVM82 plasmid isolated from epidemic strains of Yersinia
      pseudotuberculosis includes the 25MD segment, which encodes a series of
      properties affecting the virulence of the bacterium. Insertion mutants of pVM82
      containing transposition-defective Tn2507 with a kanamycin-resistance marker in
      different Hind III fragments of the 25MD segment were obtained. By recombination
      between two homologous pVM82 containing genetic markers in different parts,
      deletion derivatives of pVM82 plasmid and insertions of the plasmid segment,
      carrying kanamycin-resistance marker, into a chromosome were obtained. Results
      were obtained suggesting the presence in the plasmid 25MD segment of a transposon
      like structure capable of migrating from pVM82 plasmid onto a chromosome and from
      a chromosome and pVM82 onto pRP1.2 plasmid of a broad host range.

PMID- 7590201
TI  - [Mapping chromosomes of Erwinia carotovora subsp. Atroseptica 3-2].
AB  - Two Hfr-like donor strains of bacteria Erwinia carotovora subsp. atroseptica
      (Eca) 3-2 were developed by integration into the chromosome of the conjugative
      plasmid R471a via homology with transposon Tn9. Using these and two donor strains
      created earlier, we constructed the genetic map of a fragment of the chromosome
      of strain Eca 3-2. The location of 14 loci is shown in this map.

PMID- 7590202
TI  - [Antimutagenic action of bacterial culture liquid on mutagenesis induced by 2
      nitrofluorene in Salmonella typhimurium strains].
AB  - It was shown that cell extracts and cells of Streptococcus faecalis decrease the
      mutagenic effect of 2-nitrofluorene in Salmonella typhimurium strain TA1538 by 73
      and 48%, respectively. Cell extracts and cells of Bifidobacterium bifidum and
      Propionibacterium shermanii exhibited weak antimutagenic activity. No
      antimutagenic effect was found in Escherichia coli AB1157, Lactobacillus
      delbrueckii, or Streptococcus thermophilus. Antimutageneicity of the cell extract
      of Str. faecalis is both associated with extracellular factors interacting with 2
      nitrofluorene (desmutagenesis) and with factors affecting intracellular processes
      of mutagen biotransformation and mutation induction. Thiol compounds produced by
      growing Str. faecalis may be desmutagenic factors. A relatively heat-stable
      substance or substances of a peptide nature with a MM less than 12 kDa are
      antimutagenic factors affecting intracellular processes of mutagenesis.

PMID- 7590203
TI  - [Comparative analysis of patterns of localization of mobile genetic elements in
      genetic selection experiments on Drosophila melanogaster].
AB  - A comparative selection-genetic analysis of three heterogeneous lines of
      Drosophila melanogaster with an interrupted longitudinal wing vein was performed.
      In the control line, riC, and two selection lines, riSP and riSN, overall
      patterns of localization of six families mobile genetic elements (MGE) (MGE)
      (MDG1, MDG2, MDG3, MDG4, copia, and 297) were compared. In all, the lines
      contained 220 sites (copies) in 153 segments of the Bridges' map. According to
      response to selection, six classes of sites were identified: strong positive (P),
      weak positive (p), neutral (n), weak negative (n), strong negative (N), and
      abnormal (A). More than 50% of the sites (P+N+p+n) were shown to respond to
      selection; the contrasting classes (P and N and p and n) counterbalanced each
      other. These sites are assumed to mark actual parts of the genome, where
      polygenes are located. In other words, more than 50% of the total number of the
      genome sites act as polygenes controlling this quantitative character and respond
      to selection. Pleiotropy of polygenes in such a system must be very high. 22.2%
      of sites are neutral (class 0); apparently, they do not mark polygenes. The
      remaining 21.8% of sites (class A) show an anomalous response to selection. They
      are assumed to mark the polygenes of another genetic system, which participated
      in the maintenance of homeostasis in the original line riC. On the basis of this
      evidence, the concept of oligogenes and polygenes is developed. Oligogenes and
      polygenes are genes that occupy respectively limiting and nonlimiting positions
      in systems of expression. Adaptive properties of oligogenes are evaluated first
      and evolve rapidly. Adaptive properties of polygenes are evaluated only with
      regard to their total set and are limited by oligogenes. Variation of polygenic
      systems is generated by polygenic combination and spontaneous transpositions and
      excisions of MGE.

PMID- 7590204
TI  - [A genetic analysis of mutant chromosomes 3 with a similar spectrum of phenotypic
      action from geographically distant populations of Drosophila melanogaster].
AB  - From geographically distant populations of Drosophila melanogaster, the following
      mutant phenotypes with a wide spectrum of similar phenotypic variation were
      isolated: #89300 and #89386 from a population of Uman' (Ukraine) in 1989, and
      #920017, #921314, and #921503 from a population of Gorno-Altaisk (Altai) in 1992.
      A similar mutant phenotype (line #i13) was obtained by gamma-irradiation of the
      laboratory line Canton S. Phenotypic changes involve eye shape and structure,
      morphology of body appendages (wings, legs, and antennae), and fertility. Genetic
      analysis of mutations #89300 and #89386 showed that they belong to the third
      linkage group. Chromosomes 3 of mutants #89300 and #89386 carry inversions
      In(3R)92D-98F and In(3R)89F-95A, respectively. A complementation test for
      allelism of the isolated mutations among themselves and with several laboratory
      lines was conducted. The mutant phenotypical effect of the chromosomes isolated
      is assumed to be related to geographic variants of alleles of two closely linked
      genes, rotund and roughened eye and claret.

PMID- 7590205
TI  - [Interlineage differences in murine sensitivity to thiotepa: an experiment with
      recombinant strains].
AB  - The study is devoted to the clastogenic effect of thio-TEPA in raising
      recombinant strains 1 x C3 in mice (obtained from 101/H x C3H/Sn crossing). By
      the summer of 1993, 15 strains had reached 10 generations of inbreeding. From
      five to six siblings of each strain (males and females) aged 6-8 weeks were
      treated with the mutagen (3 mg per kg, i/p). Strain sensitivity was estimated by
      the proportion of marrow cells exhibiting chromosome lesions (including gaps).
      According to this characteristic, the strains were divided into two unequal
      groups. The first one included 12 less-sensitive strains (chromosome aberrations
      were present, on average, in 33.5% of the cells, and lay in the range from 27.0
      +/- 4.5 to 39.8 +/- 4.9). The second group included three more-sensitive strains
      with 51.2, 51.7, and 59.5% of the cells being affected (54.1% on average). A
      similar difference between the groups was found with respect to the number of
      breaks per cell: 1.15 in resistant strains and 2.88 in sensitive ones. This
      difference was significant and similar to that found earlier for C3H and 101
      strains. Thus, the results obtained support the hypothesis that mice of the 101/H
      strain carry a gene enhancing sensitivity to chemical mutagens (mut-1). Some
      strains of the first group were eliminated; the remaining ones will be bred until
      the 20th generation, when they will be investigated again in more detail.

PMID- 7590206
TI  - [Genetic divergence of certain indigenous and commercial breeds of Eurasian
      cattle (Bos taurus)].
AB  - The genetic distances between cattle breeds were calculated and relationships
      between these breeds were analyzed on the basis of polymorphism of genes encoding
      seven blood proteins (N = 22 breeds) and four milk proteins (N = 14 breeds). The
      study was performed using cluster and cladistic analysis, as well as
      multidimensional scaling. The conventional systems of classification of cattle
      breeds are reviewed in genetic terms, and the history of breeds and their
      evolution are discussed.

PMID- 7590207
TI  - [Cytogenetic effects in adolescent children from various regions of the
      Kemerovskaia district].
AB  - Considerable variations in the frequency of spontaneous chromosomal aberrations
      were revealed during a cytogenetic study of two groups of adolescents from
      ecologically different areas of Kemerovskaya oblast'. In a sample of adolescents
      living in an industrial center (the Kemerovo city), this parameter (1.4 +/-
      0.37%) did not exceed the population average value, whereas adolescents of the
      same age from a mountain region with sparse industry (the town of Tashtagol)
      exhibited, on average, a frequency of 5.87 +/- 0.62%. An increased proportion of
      chromosomal-type aberrations in the qualitative spectrum of cytogenetic damage,
      which was observed for the group of adolescents from Tashtagol, suggests that
      this population was exposed to radiation.

PMID- 7590208
TI  - [Association of nucleotide substitutions in the cytochrome b gene and regulatory
      region in types of human mitochondrial DNA].
AB  - Nucleotide sequences of the cytochrome b gene fragment of the mitochondrial DNA
      (mtDNA) between primers b1 and b2 were determined in eleven eastern Slavs. The
      group analyzed consisted of samples that differed in the hypervariable segment I
      (HVSI) of the mtDNA control region by one to seven nucleotide substitutions.
      Three types of the b1-b2 segment of the cytochrome b gene were registered. A lack
      of correlation between diversity in the coding (cytochrome b gene) and noncoding
      (HVSI) regions of mtDNA was shown. Association between substitutions at positions
      14905 bp in cytochrome b gene, and also 16126 bp and 16294 bp in the control
      region of mtDNA, was found.

PMID- 7590209
TI  - [Mitochondrial DNA markers and the problem of origin of populations from the Indo
      European linguistic family].
AB  - Data on the polymorphism of mitochondrial DNA (mtDNA) in the Caucasoid
      populations, including Eastern Slavs living in Russia, were analyzed. For
      populations of the Indo-European linguistic family, a correlation was
      demonstrated between the mtDNA marker types BamH I-3/Ava II-9 (or -13)/Msp I-4
      and the linguistic group to which the population belonged. The data on the
      geographic distribution of the marker Indo-European mtDNA types in different
      populations throughout the world and the genetic similarity of Caucasoid
      populations of the Middle East, Italy, and Russia were analyzed with respect to
      the types of the control region of mtDNA. The results confirm the hypothesis of
      Ammerman and Cavalli-Sforza about the spreading of the farming culture in Europe
      in the course of migration of Caucasoids of Middle Eastern origin in the early
      Neolithic periodic period. To test the hypotheses on the origin of Indo-Europeans
      and Indo-European languages with the use of mtDNA markers, additional information
      on mtDNA polymorphism in the world of Caucasoid populations is required.

PMID- 7590211
TI  - [Cloning, expression, and regulation of tissue-specific genes in Drosophila].
AB  - The family of esterase genes was studied in various Drosophila species. These
      genes are classified into tissue-specific and housekeeping ones. The expression
      of tissue-specific esterases in the male reproductive system of Drosophila
      species from the virilis and melanogaster groups was thoroughly examined.
      Modifier genes controlling activity level, time of synthesis, and distribution in
      cells of the tissue-specific esterase isozyme from the ejaculatory bulb were
      revealed. The structural gene coding for this enzyme was isolated, cloned, and
      sequenced. This gene was shown to be similar in different Drosophila species; the
      transcriptional level of tissue specificity of this gene was determined. The
      possibility of transforming the tissue-specific gene into a housekeeping one was
      demonstrated. In different Drosophila species, this gene can be expressed in
      different parts of the reproductive system. In transgenic males carrying the gene
      of another species the foreign gene is expressed as in the donor.

PMID- 7590210
TI  - [Analysis of allelic variants of the hypervariable locus of apolipoprotein B in
      Bashkir and Komi populations].
AB  - Allelic variation of the hypervariable apolipoprotein B gene locus (ApoB) in
      three groups of the Bashkir population and in the Komi population was analyzed.
      Among 219 individuals studied, 13 allelic variants were identified with the
      number of repeats ranging from 28 to 52. The frequency of alleles varied from
      0.01 to 0.51 with the mean heterozygosity index being 0.66 in the Bashkir
      population and 0.74 in the Komi one. Considerable difference in the frequency
      distribution of the ApoB loci genotypes between the Bashkir and Komi populations
      was observed, and the distribution patterns for Bashkirs from Abzelilovskii and
      Ilishevskii regions deviated from the Hardy-Weinberg equilibrium. The genetic
      distance between the Bashkir and Komi populations calculated on the basis of
      allele frequencies at the hypervariable ApoB gene locus corresponded to the
      expected degree similarity of the populations studied. Thus, this locus can be
      recommended as an informative marker for studying the gene pool and genetic
      processes in the populations because of the high level of its polymorphism and
      the heterozygosity in the populations.

PMID- 7590213
TI  - [A circular genetic map of chromosomes from Erwinia carotovora subsp. Atroseptica
      3-2].
AB  - A circular genetic map of the bacterium Erwinia carotovora subsp. atroseptica 3-2
      was constructed on the basis of the R471a plasmid and Tn5 and Tn9 using Hfr-like
      donors. Forty-six genes, including phytopathogenicity genes, were located on the
      basis of interrupted mating experiment results and analysis of coinheritance of
      markers on a map of 183 min in length. The similarity and differences of
      chromosomal genetic maps of Erwinia genus bacteria are discussed.

PMID- 7590212
TI  - [Inheritable phenotypic normalization of rodent cells transformed by simian
      adenovirus SA7 E1 oncogenes by singled-stranded oligonucleotides complementary to
      a long region of integrated oncogenes].
AB  - G11 mouse cells and SH2 rat cells transformed with simian adenovirus SA7 DNA
      showed inheritable oncogen-specific phenotypic normalization when treated with
      sense and antisense oligonucleotides complementary to long RNA sequences, plus or
      minus strands of the integrated adenovirus oncogenes E1A and E1B. Transitory
      treatment of the cells with the oligonucleotides in the absence of serum was
      shown to cause the appearance of normalized cell lines with fibroblastlike
      morphology, slower cell proliferation, and lack of ability to form colonies in
      soft agar. Proliferative activity and adhesion of the normalized cells that
      established cell lines were found to depend on the concentration of growth
      factors in the cultural medium. In some of the cell lines, an inhibition of
      transcription of the E1 oncogenes was observed. The normalization also produced
      cells that divided 2 - 5 times and died and cells that reverted to a transformed
      phenotype in 2 - 10 days. The latter appeared predominantly upon the action of
      the antisense oligonucleotides.

PMID- 7590215
TI  - [Origin and properties of Pseudomonas aeruginosa PAO1 clones surviving after
      induction of prophages-transposons].
AB  - Various mutations cancelling the lethal effect of phage lytic development and
      simultaneous phenotypic modifications were found in rare clones surviving after
      incubation at 42 degrees C of Pseudomonas aeruginosa (D3112 cts 15), lysogenic
      for thermoinducible mutant cts 15 of the transposable prophage (TP) D3112. All
      mutations arose prior to thermal induction. Temperature induction of other
      bacteriophages (nontransposable) did not lead to selection of bacterial
      morphological mutants. Therefore, it was concluded that mutagenesis occurred upon
      the partial (reversible) TP derepression accompanied by coupled replication
      transposition of TP, the latter being the direct cause of the mutator effect.
      Isolation of the P. aeruginosa PAO1 mutant R10 (this mutant is resistant to
      infection with TP at 42 degrees C) allowed the proper selection and examination
      of numerous survivors. Comparison of their types derived from lysogens with
      different prophage location indicated that the number of secondary sites where TP
      integration is possible without the loss of cell viability is limited. Several
      transposition events occurred in the history of some survivors (during a repeated
      or single derepression event). Type D clones, which produce small colonies, are
      of special interest, because mechanisms underlying the survival of such clones
      are extremely diverse, and their phenotypes indicate the possibility of stable
      chromosomal rearrangements in the genome of P. aeruginosa.

PMID- 7590214
TI  - [Selective inhibition of DNA amplification in nonadhesive cultures of Mycoplasma
      pneumoniae].
AB  - Inhibition of amplification of various genome regions of Mycoplasma pneumoniae
      was observed in the polymerase chain reaction, and was dependent on cultivation
      conditions. A protein stably associated with DNA is responsible for the
      inhibitory effect. It is assumed that when the protein selectively associates
      with separate DNA regions, it can inhibit genes encoding pathogenicity factors,
      thus promoting mycoplasma transformation into persistent variants.

PMID- 7590217
TI  - [Genetics of unstable alleles of X-chromosome genes isolated during the outburst
      of the yellow mutation in 1982-1991 in the natural population of Drosophila
      melanogaster in Umani].
AB  - In 1982, a local increase of frequency of mutation yellow-2, which lasted for a
      decade, occurred in a population of Drosophila melanogaster from Uman' (Ukraine).
      Genetic properties (phenotypic difference, mutability, and peculiarities of
      complementation) of alleles yellow-2, isolated from the population during the
      mutation outburst, and of their revertants, were studied. Allelic diversity,
      which reflected molecular differences in allele structure, was shown to appear.
      In addition to mutation yellow, isolated in 1990 from the Uman' population,
      mutational properties of other sex-linked genes (dusky, miniature, rudimentary,
      singed, and vermilion) isolated from natural populations in 1986 to 1990, were
      analyzed. Based on these data, the conclusion was drawn that the presence of
      unstable alleles in populations is not a sufficient condition for mutation
      outbursts. Comparative analysis of properties of the alleles, obtained in
      different periods of the outburst, continues.

PMID- 7590216
TI  - [Isolation and characteristics of Salmonella typhimurium mutants with a disrupted
      process of generating nonculturable forms].
AB  - A laboratory model of the induction of nonculturable forms in Salmonella
      typhimurium has been developed. Mutants of S. typhimurium were obtained using
      insertion mutagenesis via the TnPhoA transposon. These mutants were impaired in
      the cell transition from the vegetative to the nonculturable state assayed in
      this model. Mutants have various phenotypes and are located in different regions
      of the chromosome, as shown by the data obtained using pulsed-field
      electrophoresis of genomic DNA.

PMID- 7590219
TI  - [High resolution GTG banding and nucleolus organizer regions of chromosomes from
      the vole Microtus kirgisorum].
AB  - The use of GTG-banding of chromosomes in combination with the pipette method of
      chromosome preparation at the early metaphase made it possible to distinguish
      about 520 segments in the haploid chromosome set of vole Microtus kirgisorum. The
      ideogram of M. kirgisorum chromosomes was obtained on the basis of detailed
      investigation of chromosomes at different condensation levels. Data of the
      localization and the number of nucleolus-organizer regions are given.

PMID- 7590220
TI  - [Genetic position of Mordvinians among other Finno-Ugrian peoples].
AB  - Two different tribes of Mordvinians, Erzia and Moksha, were studied with respect
      to 13 different genetic marker systems. The Erzia and Moksha were shown to be
      fairly homogeneous; a significant gene frequency difference was found only in the
      MN blood group system. Estimation of the genetic distances revealed that
      Mordvinians showed the closest relationship to the Maris and to populations of
      the western Finno-Ugrian linguistic group such as Finns, Estonians and Karelians.

PMID- 7590221
TI  - [Hand dermatoglyphics in patients with isolated triphalangia and Holt-Oram
      syndrome].
AB  - A comparative analysis of dermatoglyphic prints of patients with the Holt-Oram
      syndrome and isolated triphalangeal thumbs was performed with control
      dermatoglyphics. A specific feature of the syndrome is a change in the main
      palmar lines and their termination on the radial border of the hand not only in
      the absence of the thumb but also in the case of formation of the abortive xT
      line, its radiants, and the axial triradius. This trait may be considered
      diagnostic for the Holt-Oram syndrome. Cases of triphalangeal thumbs with
      preaxial polydactyly do not reveal significant changes in dermatoglyphic patterns
      and appear to result from partial duplication of the thumb. An isolated
      triphalangeal thumb may be the result of an atavistic development of homeotic
      transformation of the thumb.

PMID- 7590224
TI  - [Establishing a gene linkage phase by parental phenotype].
AB  - The possibility of using the phenotypic characteristics of parents for
      identifying the linkage phase in offspring is analyzed. It is demonstrated that
      parents with similar phenotypes (or marker genotypes) carry no information about
      the gene linkage phase in diheterozygous offspring. The probability of a certain
      linkage phase remains the same in all informative crossings. It depends on the
      model of inheritance of the analyzed alternative trait and is similar for di- and
      polyallelic markers. The frequencies of informative crossings and the probability
      of the linkage phase for different models of inheritance of the analyzed and
      marker traits are estimated.

PMID- 7590222
TI  - [Genetic-demographic study of mountain populations of Daghestan and migrants from
      it to the lowlands. Study of genetic and marital structure].
AB  - The results of a genetic and demographic study of two "split" isolates of small
      native ethnic groups of Daghestan are described. Parts of these populations were
      resettled from habitual highland ecological conditions to radically new lowland
      conditions in the 1940s. These split isolates were compared with a population of
      native inhabitants of the Daghestan lowland. It was found that, since resettling,
      separated populations originating from split isolates became significantly
      different in both marriage and genetic structures. This is manifested in
      different phenotypic and allelic frequencies of a number of physiological and
      biochemical markers and in levels of their heterozygosity. To explain the
      differences revealed, a hypothesis was proposed about the relationship between
      levels of inbreeding, heterozygosity, and physiologic sensitivity that account
      for the differential adaptability of members of the isolated populations to
      changing environmental conditions. This is the first report of a series of papers
      describing the experimental testing of this hypothesis. While testing the
      validity of the hypothesis in this study, a positive linear correlation was found
      between inbreeding and homozygosity levels.

PMID- 7590223
TI  - [Interval estimates of combinatorial measures of similarity for orders of
      homologous genes].
AB  - A procedure was developed for establish the confidence intervals for point
      estimates of a quantitative measure of similarity of genomes. Reasons for its use
      in genetic studies are demonstrated. The algorithm for this procedure and
      derivation of calculating formulas are described. Results of testing them using
      simulation genetic experiments are shown. As an example, interval estimates of
      the similarity measures for three genomes have been obtained.

PMID- 7590218
TI  - [Study of polymorphism and divergence of genomic DNA at the species and
      population levels (using DNA of domestic sheep and wild rams as an example)].
AB  - Genetic divergence in repetitive sequences of nuclear DNA of wild and domestic
      sheep was studied by general restriction endonuclease mapping (i.e., the
      taxonoprint method). The PCR RAPD method with one and two arbitrary primers was
      also used to analyze the nuclear DNA polymorphism in some other regions. The
      taxonoprint method, performed using six endonucleases, showed specificity and
      virtually complete similarity in the patterns of repetitive DNA sequences of two
      wild forms, argali and mouflon, and five domestic sheep breeds. Central Asian
      breeds, Kazakh fine-fleeced, karakul, ghissar, and eadeelbay, and an English
      breed, Lincoln, were examined. The results confirm the opinion that wild and
      domestic sheep may be considered one polytypic species. The PCR-RAPD method, both
      with one and two arbitrary primers, revealed a closer similarity of all the sheep
      breeds examined when argali, rather than with mouflon, was used. These results
      indicate that the domestication area of sheep was much broader than was earlier
      presumed. Otherwise, hybridizations of domestic and wild forms could occasionally
      occur in the area of their coexistence. The amplification patterns of PCR-RAPD
      products are the most promising population genetic markers.

PMID- 7590225
TI  - [A new point mutation in the mitochondrial gene ND1, detected in a patient with
      type II diabetes].
AB  - A novel mutation in a mitochondrial gene was identified in a patient with type II
      diabetes mellitus. G-to-A transition was localized at the nt3316 position of gene
      ND1 and resulted in alanine threonine replacement at position 4 of mitochondrial
      NAD-H-dehydrogenase.

PMID- 7590226
TI  - The HCF repeat is an unusual proteolytic cleavage signal.
AB  - The herpes simplex virus VP16-associated protein HCF is a nuclear host-cell
      factor that exists as a family of polypeptides encoded by a single gene. The
      mature HCF polypeptides are amino- and carboxy-terminal fragments of a large
      approximately 300-kD precursor protein that arise through cleavage at one or more
      centrally located sites. The sites of cleavage are the HCF repeats, highly
      conserved 26-amino-acid sequences repeated six times in the HCF precursor
      protein. The HCF repeat alone is sufficient to induce cleavage of a heterologous
      protein, and cleavage occurs at a defined site--PPCE/THET--within the HCF repeat.
      Alanine-scan mutagenesis was used to identify a large 18-amino-acid segment of
      the HCF repeat that is important to induce cleavage of a heterologous protein.
      Even though HCF is cleaved, the majority of amino- and carboxy-terminal cleavage
      products remain tightly, albeit noncovalently, associated. Modulation of this
      noncovalent association may provide a mechanism for regulating HCF activity. For
      example, the cleaved products of an alternative mRNA splicing variant of HCF do
      not remain associated.

PMID- 7590227
TI  - Integrated control of seed maturation and germination programs by activator and
      repressor functions of Viviparous-1 of maize.
AB  - The Viviparous-1 (VP1) transcriptional activator of maize is required for
      abscisic acid induction of maturation-specific genes late in seed development
      leading to acquisition of desiccation tolerance and arrest in embryo growth.
      Here, we show that VP1 also inhibits induction of the germination-specific alpha
      amylase genes in aleurone cells of the developing seed and thereby appears to be
      involved in preventing precocious hydrolyzation of storage compounds accumulating
      in the endosperm. In developing seeds of the somatically instable vp1-m2 mutant,
      hydrolase activity was derepressed specifically in endosperm sectors underlying
      vp1 mutant aleurone. A barley alpha-amylase promoter-GUS reporter construct (Amy
      GUS) was induced in developing vp1 mutant aleurone cells but not in wild-type
      aleurone cells. Moreover, transient expression of recombinant VP1 and vp1 mutant
      aleurone cells strongly inhibited expression of Amy-GUS and thus effectively
      complemented this aspect of the mutant phenotype. VP1 specifically repressed
      induction of Amy-GUS by the hormone gibberellic acid in aleurone of germinating
      barley seeds. Deletion of the acidic transcriptional activation domain of VP1 did
      not affect the inhibitory activity, indicating that VP1 has a discrete repressor
      function. Hence, physically combining activator and repressor functions in one
      protein may provide a mechanism to integrate the control of two normally
      consecutive developmental programs, seed maturation and seed germination.

PMID- 7590228
TI  - The 18S rRNA dimethylase Dim1p is required for pre-ribosomal RNA processing in
      yeast.
AB  - The m6(2)A1779m6(2)A1780 dimethylation at the 3' end of the small subunit rRNA
      has been conserved in evolution from bacteria to eukaryotes. The yeast 18S rRNA
      dimethylase gene DIM1 was cloned previously by complementation in Escherichia
      coli and shown to be essential for viability in yeast. A conditional GAL10::dim1
      strain was constructed to allow the depletion of Dim1p from the cell. During
      depletion, dimethylation of the pre-rRNA is progressively inhibited and pre-rRNA
      processing at cleavage sites A1 and A2 is concomitantly lost. In consequence, the
      mature 18S rRNA and its 20S precursor drastically underaccumulate. This has the
      effect of preventing the synthesis of nonmethylated rRNA. To test whether the
      processing defect is a consequence of the absence of the dimethylated nucleotides
      or of the Dim1p dimethylase itself, a cis-acting mutation was created in which
      both dimethylated adenosines are replaced by guanosine residues. Methylation
      cannot occur on this mutant pre-rRNA, but no clear pre-rRNA processing defect is
      seen. Moreover, methylation of the wild-type pre-rRNA predominantly occurs after
      cleavage at sites A1 and A2. This shows that formation of the
      m6(2)A1779m6(2)A1780 dimethylation is not required for pre-rRNA processing. We
      propose that the binding of Dim1p to the pre-ribosomal particle is monitored to
      ensure that only dimethylated pre-rRNA molecules are processed to 18S rRNA.

PMID- 7590229
TI  - Cappuccino, a Drosophila maternal effect gene required for polarity of the egg
      and embryo, is related to the vertebrate limb deformity locus.
AB  - We report the molecular isolation of cappuccino (capu), a gene required for
      localization of molecular determinants within the developing Drosophila oocyte.
      The carboxy-terminal half of the capu protein is closely related to that of the
      vertebrate limb deformity locus, which is known to function in polarity
      determination in the developing vertebrate limb. In addition, capu shares both a
      proline-rich region and a 70-amino-acid domain with a number of other genes, two
      of which also function in pattern formation, the Saccharomyes cerevisiae BNI1
      gene and the Aspergillus FigA gene. We also show that capu mutant oocytes have
      abnormal microtubule distributions and premature microtubule-based cytoplasmic
      streaming within the oocyte, but that neither the speed nor the timing of the
      cytoplasmic streaming correlates with the strength of the mutant allele. This
      suggests that the premature cytoplasmic streaming in capu mutant oocytes does not
      suffice to explain the patterning defects. By inducing cytoplasmic streaming in
      wild-type oocytes during mid-oogenesis, we show that premature cytoplasmic
      streaming can displace staufen protein from the posterior pole, but not gurken
      mRNA from around the oocyte nucleus.

PMID- 7590231
TI  - Misexpression of Hoxa-13 induces cartilage homeotic transformation and changes
      cell adhesiveness in chick limb buds.
AB  - During chick limb development, the Abd-B subfamily of genes in the HoxA cluster
      are expressed in a region-specific manner along the proximodistal axis. To
      elucidate the function of Hoxa-13 that is expressed in the autopod during normal
      limb development, Hoxa-13 was misexpressed in the entire limb bud with a
      replication-competent retroviral system. Misexpression of Hoxa-13 resulted in a
      remarkable size reduction of the zeugopodal cartilages as a result of the arrest
      of cartilage cell growth and differentiation restricted in the zeugopod. This
      size reduction seems to be attributable to homeotic transformation of the
      cartilages in the zeugopod to the more distal cartilage, that of the
      carpus/tarsus. This transformation was specific to Hoxa-13 and was not observed
      by overexpression of other Hox genes. These results indicate that Hoxa-13 is
      responsible for switching the genetic code from long bone formation to short bone
      formation during normal development. When the limb mesenchymal cells were
      dissociated and cultured in vitro, Hoxa-13-expressing limb mesenchymal cells
      reassociated and were sorted out from nonexpressing cells. Forced expression of
      Hoxa-13 at the stage that endogenous Hoxa-13 was not expressed as of yet altered
      the homophilic cell adhesive property. These findings indicate the involvement of
      Hoxa-13 in determining homophilic cell-to-cell adhesiveness that is supposed to
      be crucial for the cartilage pattern formation.

PMID- 7590230
TI  - Homeless is required for RNA localization in Drosophila oogenesis and encodes a
      new member of the DE-H family of RNA-dependent ATPases.
AB  - The homeless (hls) gene of Drosophila is required for anteroposterior and
      dorsoventral axis formation during oogenesis. At a low frequency, females
      homozygous for mutations in hls generate early egg chambers in which the oocyte
      is positioned incorrectly within the cyst. At a high frequency, late-stage egg
      chambers exhibit a ventralized chorion. Sequence analysis of the hls cDNA
      predicts a protein with amino-terminal homology to members of the DE-H family of
      RNA-dependent ATPases and putative helicases. Similarity of 51% in the amino
      terminal third of the protein was found to two yeast splicing factors, PRP2 and
      PRP16, and to Drosophila Maleless, which is required for dosage compensation. To
      analyze Hls function, RNA localization patterns were determined for seven
      different transcripts in hls mutant ovaries. Previtellogenic transport to the
      oocyte was unaffected for all transcripts examined. Transport and localization of
      bicoid and oskar messages during vitellogenic stages were strongly disrupted, and
      the distribution and/or quantity of gurken, orb, and fs(1)K10 mRNAs were also
      affected, but to a lesser degree. In contrast, hu-li tai shao and Bicaudal-D
      transcripts were transported and localized normally in hls mutants. In addition,
      Kinesin heavy chain:beta-Galactosidase fusion protein failed to localize
      correctly to the posterior of the oocyte in vitellogenic egg chambers.
      Examination of the microtubule structure with anti-alpha-Tubulin antibodies
      revealed aberrant microtubule organizing center movement and an abnormally dense
      cytoplasmic microtubule meshwork. We discuss potential roles for Hls in
      organizing a cytoskeletal framework essential for localizing specific RNAs.

PMID- 7590234
TI  - Enhancer-independent variants of phage Mu transposase: enhancer-specific
      stimulation of catalytic activity by a partner transposase.
AB  - Assembly of the functional tetrameric form of phage Mu transposase (A protein)
      requires specific interactions between the Mu A monomer and its cognate sequences
      at the ends of the Mu genome (attL and attR) as well as those internal to it (the
      enhancer element). We describe here deletion variants of Mu A that show enhancer
      independence in the assembly of the strand cleavage complex. These deletions
      remove the amino-terminal region of Mu A required for its interactions with the
      enhancer elements. The basal enhancer-independent activity of the variant
      proteins can be stimulated by a partner variant harboring an intact enhancer
      binding domain. By exploiting the identical att-binding, and nonidentical
      enhancer-binding specificities of Mu A and D108 A (transposase of the Mu related
      phage D108), we show that the stimulation of activity is enhancer-specific. Taken
      together, these results suggest that the domain of Mu A that includes the
      enhancer-interacting region may exert negative as well as positive modulatory
      effects on the strand cleavage reaction. We discuss the implications of these
      results in the framework of a recent model for the assembly of shared active
      sites within the Mu A tetramer.

PMID- 7590232
TI  - Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and
      second branchial arch derivatives and abnormal differentiation in the forebrain.
AB  - Genetic analysis of the development and evolution of the vertebrate head is at a
      primitive stage. Many homeo box genes, including the Distal-less family, are
      potential regulators of head development. To determine the function of Dlx-2, we
      generated a null mutation in mice using gene targeting. In homozygous mutants,
      differentiation within the forebrain is abnormal and the fate of a subset of
      cranial neural crest cells is respecified. The latter causes abnormal
      morphogenesis of the skeletal elements derived from the proximal parts of the
      first and second branchial arches. We hypothesize that the affected skull bones
      from the first arch have undergone a transformation into structures similar to
      those found in reptiles. These results show that Dlx-2 controls development of
      the branchial arches and the forebrain and suggests its role in craniofacial
      evolution.

PMID- 7590233
TI  - Similarities between trunk and spatzle, putative extracellular ligands specifying
      body pattern in Drosophila.
AB  - The basic body plan of Drosophila is specified by four determinant systems that
      organize pattern along the anteroposterior and dorsoventral axes. Two of these
      systems (anterior and posterior) depend on localized mRNAs. In contrast, the
      other two (ventral and terminal) require locally generated extracellular ligands
      that are transduced, respectively, by the transmembrane receptors Toll and torso
      (tor). The ligand for the Toll receptor is thought to be spatzle (spz), a
      secreted protein that is activated by proteolytic cleavage. Here we report that
      trunk (trk), a gene required for activity of the tor receptor, encodes a protein
      that resembles spz in several respects. In particular, the sequence suggests that
      trk is a secreted protein and that it contains an internal site for proteolytic
      cleavage. Furthermore, the carboxy-terminal domain of trk has a similar
      arrangement of cysteines to that of spz. We propose that trk encodes an
      extracellular ligand involved in specifying terminal body pattern and suggest by
      analogy with spz that a cleaved form of trk constitutes the ligand for the tor
      receptor.

PMID- 7590235
TI  - Enhanced and coordinated processing of synapsed viral DNA ends by retroviral
      integrases in vitro.
AB  - We have designed novel substrates to investigate the first step in retroviral
      integration: the site-specific processing of two nucleotides from the 3' ends of
      viral DNA. The substrates consist of short duplex oligodeoxynucleotides whose
      sequences match those of the U3 and U5 ends of viral DNA but are covalently
      synapsed across the termini by short, single-strand nucleotide linkers. We show
      here that the optimal separation between termini in a synapsed-end substrate for
      avian sarcoma/leukosis virus (ASV) IN is 2 nucleotides. This places the two
      conserved 5'-CA-3' processing sites 6 nucleotides apart, a separation equal to
      the staggered cut in target DNA produced by this enzyme during the subsequent
      joining reaction. Based on estimates of initial reaction rates, this synapsed-end
      substrate is processed by IN at > 10-fold higher efficiency than observed with an
      equivalent mixture of U3 and U5 single-end (uncoupled) substrates. Enhanced
      processing is maintained at low IN concentrations, suggesting that the synapsed
      end substrate may facilitate enzyme multimerization. Enhanced processing by HIV-1
      IN, which produces a 5-bp stagger during integration, was observed with a
      synapsed-end substrate in which the separation between processing sites was 5
      nucleotides. These observations provide estimates of the distances between active
      sites in the multimeric IN-DNA complexes of ASV and HIV-1. Our results also show
      that processing of paired U3 and U5 ends need not be coupled temporally. Finally,
      we observed that substrates that paired a wild-type with a mutated terminus were
      cleaved poorly at both ends. Thus, in vitro processing of the synapsed-end
      substrates requires specific recognition of the sequences at both ends. These
      findings provide new insights into the mechanism of integrative recombination by
      retroviral integrases and, by extension, other prokaryotic and eukaryotic
      transposases that are related to the viral enzymes.

PMID- 7590236
TI  - Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase
      and modulates c-Abl transforming activity.
AB  - A protein has been identified that interacts specifically with both the Src
      homologous 3 (SH3) domain and carboxy-terminal sequences of the c-Abl tyrosine
      kinase. The cDNA encoding the Abl interactor protein (Abi-2), was isolated from a
      human lymphocyte library using the yeast two-hybrid system with the Abl SH3
      domain as bait. Abi-2 binds to c-Abl in vitro and in vivo. Abi-2 is a novel
      protein that contains an SH3 domain and proline-rich sequences critical for
      binding to c-Abl. A basic region in the amino terminus of Abi-2 is homologous to
      the DNA-binding sequence of homeo-domain proteins. We show that Abi-2 is a
      substrate for the c-Abl tyrosine kinase. Expression of an Abi-2 mutant protein
      that lacks sequences required for binding to the Abl SH3 domain but retains
      binding to the Abl carboxyl terminus activates the transforming capacity of c
      Abl. The properties of Abi-2 are consistent with a dual role as regulator and
      potential effector of the c-Abl protein and suggest that Abi-2 may function as a
      tumor suppressor in mammalian cells.

PMID- 7590237
TI  - Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of
      the Abl protein, suppresses v-abl transforming activity.
AB  - A novel cellular protein, Abl-interactor-1 (Abi-1), which specifically interacts
      with the carboxy-terminal region of Abl oncoproteins, has been identified in a
      mouse leukemia cell line. The protein exhibits sequence similarity to homeotic
      genes, contains several polyproline stretches, and includes a src homology 3
      (SH3) domain at its very carboxyl terminus that is required for binding to Abl
      proteins. The abi-1 gene has been mapped to mouse chromosome 2 and is genetically
      closely linked to the c-abl locus. The gene is widely expressed in the mouse,
      with highest levels of mRNA found in the bone marrow, spleen, brain, and testes.
      The Abi-1 protein coimmunoprecipitates with v-Abl and serves as a substrate for
      kinase activity. When overexpressed in NIH-3T3 cells, abi-1 potently suppresses
      the transforming activity of Abelson leukemia virus expressing the full-length
      p160v-abl kinase but does not affect the transforming activity of viruses
      expressing a truncated p90v-abl or v-src kinases. We suggest that the Abi-1
      protein may serve as a regulator of Abl function in transformation or in signal
      transduction.

PMID- 7590238
TI  - The neurogenic suppressor of hairless DNA-binding protein mediates the
      transcriptional activation of the enhancer of split complex genes triggered by
      Notch signaling.
AB  - The Notch protein (N) acts as a transmembrane receptor for intercellular signals
      controlling cell fate choices in vertebrates and invertebrates. The signal of N
      activation may be transduced directly from the cell surface into the nucleus by
      an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)],
      by its regulated nuclear import. Su(H) is shown here to play a direct role in the
      immediate response of the genome to N signaling in Drosophila. First, Su(H)
      mutant embryos derived from mutant germ-line clones exhibited a "neurogenic"
      phenotype of neural hypertrophy similar to the N phenotype. Second, the lack of N
      lateral signaling in these Su(H) mutant embryos was associated with a failure to
      express the m5 and m8 genes from the Enhancer of split Complex [E(spl)-C].
      Finally, the Su(H) protein bound to the regulatory sequences of the E(spl)-C m5
      and m8 genes, and these binding sites were required for the activation of the m5
      and m8 promoters in the ventral neuroectoderm. The expression of the E(spl)-C m8
      gene was found to be similarly regulated by Su(H) during wing imaginal disc
      development. Thus, the transcriptional activation of these E(spl)-C genes by
      Su(H) appears to be a direct and relatively general response to the activation of
      N. However, we also present evidence indicating that N signals in an Su(H)
      independent manner during mesectoderm formation.

PMID- 7590239
TI  - Suppressor of hairless directly activates transcription of enhancer of split
      complex genes in response to Notch receptor activity.
AB  - We have investigated the functional relationships among three loci that are
      required for multiple alternative cell fate decisions during adult peripheral
      neurogenesis in Drosophila: Notch (N), which encodes a transmembrane receptor
      protein, Suppressor of Hairless [Su(H)], which encodes a DNA-binding
      transcription factor, and the Enhancer of split gene complex [E(spl)-C], which
      includes seven transcription units that encode basic helix-loop-helix (bHLH)
      repressor proteins. We describe several lines of evidence establishing that Su(H)
      directly activates transcription of E(spl)-C genes in response to N receptor
      activity. Expression of an activated form of the N receptor leads to elevated and
      ectopic E(spl)-C transcript accumulation and promoter activity in imaginal discs.
      We show that the proximal upstream regions of three E(spl)-C genes contain
      multiple specific binding sites for Su(H). The integrity of these sites, as well
      as Su(H) gene activity, are required not only for normal levels of expression of
      E(spl)-C genes in imaginal disc proneural clusters, but also for their
      transcriptional response to hyperactivity of the N receptor. Our results
      establish Su(H) as a direct regulatory link between N receptor activity and the
      expression of E(spl)-C genes, extending the known linear structure of the N cell
      cell signaling pathway.

PMID- 7590240
TI  - Mouse model for the lysosomal disorder galactosialidosis and correction of the
      phenotype with overexpressing erythroid precursor cells.
AB  - The lysosomal storage disorder galactosialidosis results from a primary
      deficiency of the protective protein/cathepsin A (PPCA), which in turn affects
      the activities of beta-galactosidase and neuraminidase. Mice homozygous for a
      null mutation at the PPCA locus present with signs of the disease shortly after
      birth and develop a phenotype closely resembling human patients with
      galactosialidosis. Most of their tissues show characteristic vacuolation of
      specific cells, attributable to lysosomal storage. Excessive excretion of
      sialyloligosaccharides in urine is diagnostic of the disease. Affected mice
      progressively deteriorate as a consequence of severe organ dysfunction,
      especially of the kidney. The deficient phenotype can be corrected by
      transplanting null mutants with bone marrow from a transgenic line overexpressing
      human PPCA in erythroid precursor cells. The transgenic bone marrow gives a more
      efficient and complete correction of the visceral organs than normal bone marrow.
      Our data demonstrate the usefulness of this animal model, very similar to the
      human disease, for experimenting therapeutic strategies aimed to deliver the
      functional protein or gene to affected organs. Furthermore, they suggest the
      feasibility of gene therapy for galactosialidosis and other disorders, using bone
      marrow cells engineered to overexpress and secrete the correcting lysosomal
      protein.

PMID- 7590241
TI  - Developmental-specific activity of the FGF-4 enhancer requires the synergistic
      action of Sox2 and Oct-3.
AB  - Fibroblast growth factor 4 (FGF-4) has been shown to be a signaling molecule
      whose expression is essential for postimplantation mouse development and, at
      later embryonic stages, for limb patterning and growth. The FGF-4 gene is
      expressed in the blastocyst inner cell mass and later in distinct embryonic
      tissues but is transcriptionally silent in the adult. In tissue culture FGF-4
      expression is restricted to undifferentiated embryonic stem (ES) cells and
      embryonal carcinoma (EC) cell lines. Previously, we determined that EC cell
      specific transcriptional activation of the FGF-4 gene depends on a synergistic
      interaction between octamer-binding proteins and an EC-specific factor, Fx, that
      bind adjacent sites on the FGF-4 enhancer. Through the cloning and
      characterization of an F9 cell cDNA we now show that the latter activity is Sox2,
      a member of the Sry-related Sox factors family. Sox2 can form a ternary complex
      with either the ubiquitous Oct-1 or the embryonic-specific Oct-3 protein on FGF-4
      enhancer DNA sequences. However, only the Sox2/Oct-3 complex is able to promote
      transcriptional activation. These findings identify FGF-4 as the first known
      embryonic target gene for Oct-3 and for any of the Sox factors, and offer
      insights into the mechanisms of selective gene activation by Sox and octamer
      binding proteins during embryogenesis.

PMID- 7590242
TI  - Mouse Otx2 functions in the formation and patterning of rostral head.
AB  - The anterior part of the vertebrate head expresses a group of homeo box genes in
      segmentally restricted patterns during embryogenesis. Among these, Otx2
      expression covers the entire fore- and midbrains and takes place earliest. To
      examine its role in development of the rostral head, a mutation was introduced
      into this locus. The homozygous mutants did not develop structures anterior to
      rhombomere 3, indicating an essential role of Otx2 in the formation of the
      rostral head. In contrast, heterozygous mutants displayed craniofacial
      malformations designated as otocephaly; affected structures appeared to
      correspond to the most posterior and most anterior domains of Otx expression
      where Otx1 is not expressed. The homo- and heterozygous mutant phenotypes suggest
      Otx2 functions as a gap-like gene in the rostral head where Hox code is not
      present. The evolutionary significance of Otx2 mutant phenotypes was discussed
      for the innovation of the neurocranium and the jaw.

PMID- 7590243
TI  - The generally expressed hnRNP F is involved in a neural-specific pre-mRNA
      splicing event.
AB  - The proteins and RNA regulatory elements that control tissue-specific pre-mRNA
      splicing in mammalian cells are mostly unknown. In this study, a set of proteins
      is identified that binds to a splicing regulatory element downstream of the
      neuron specific c-src N1 exon. This complex of proteins bound specifically to a
      short RNA containing the regulatory sequence in neuronal extracts that splice the
      N1 exon. It was not seen in non-neuronal cell extracts that fail to splice this
      exon. UV-cross-linking experiments identified a neuron-specific 75-kD protein and
      several nontissue-specific proteins, including the 53-kD heterogeneous nuclear
      ribonucleoprotein F (hnRNP F), as components of this complex. Although present in
      both extracts, hnRNP F binds tightly to the RNA only in the neuronal extracts. A
      mutation in the regulatory RNA sequence, that inhibits N1 splicing in vivo,
      abolished formation of the neuron-specific complex and the binding of the neuron
      specific 75-kD protein. Competition experiments in the two extracts show that the
      binding of the neuronal protein complex to the src pre-mRNA is required to
      activate N1 exon splicing in vitro. Antibody inhibition experiments indicate that
      the hnRNP F protein is a functional part of this complex. The assembly of
      regulatory complexes from both constitutive and specific proteins is likely to be
      a general feature of tissue-specific splicing regulation.

PMID- 7590244
TI  - The 160-kD subunit of human cleavage-polyadenylation specificity factor
      coordinates pre-mRNA 3'-end formation.
AB  - Cleavage-polyadenylation specificity factor (CPSF) is a multisubunit protein that
      plays a central role in 3' processing of mammalian pre-mRNAs. CPSF recognizes the
      AAUAAA signal in the pre-mRNA and interacts with other proteins to facilitate
      both RNA cleavage and poly(A) synthesis. Here we describe the isolation of cDNAs
      encoding the largest subunit of CPSF (160K) as well as characterization of the
      protein product. Antibodies raised against the recombinant protein inhibit
      polyadenylation in vitro, which can be restored by purified CPSF. Extending
      previous studies, which suggested that 160K contacts the pre-mRNA, we show that
      purified recombinant 160K can, by itself, bind preferentially to AAUAAA
      containing RNAs. While the sequence of 160K reveals similarities to the RNP1 and
      RNP2 motifs found in many RNA-binding proteins, no clear match to a known RNA
      binding domain was found, and RNA recognition is therefore likely mediated by a
      highly diverged or novel structure. We also show that 160K binds specifically to
      both the 77K (suppressor of forked) subunit of the cleavage factor CstF and to
      poly(A) polymerase (PAP). These results provide explanations for previously
      observed cooperative interactions between CPSF and CstF, which are responsible
      for poly(A) site specification, and between CPSF and PAP, which are necessary for
      synthesis of the poly(A) tail. Also supporting a direct role for 160K in these
      interactions is the fact that 160K by itself retains partial ability to cooperate
      with CstF in binding pre-mRNA and, unexpectedly, inhibits PAP activity in in
      vitro assays. We discuss the significance of these multiple functions and also a
      possible evolutionary link between yeast and mammalian polyadenylation suggested
      by the properties and sequence of 160K.

PMID- 7590246
TI  - A role for nucleosome assembly in both silencing and activation of the Xenopus TR
      beta A gene by the thyroid hormone receptor.
AB  - We have assembled the thyroid hormone-inducible promoter of the Xenopus thyroid
      hormone receptor (TR)beta A gene into chromatin using replication-coupled and 
      independent assembly pathways in vivo. We establish that heterodimers of TR and 9
      cis retinoic acid receptors (RXR) can bind to their recognition sites within
      chromatin both in vivo and in vitro and alternately repress or activate
      transcription dependent on the absence or presence of thyroid hormone. Maximal
      transcriptional repression requires the presence of unliganded TR/RXR
      heterodimers during replication-coupled chromatin assembly. We demonstrate an
      increase in transcription directed by the TR beta A promoter of over two orders
      of magnitude in vivo, following the addition of thyroid hormone. This increase in
      transcription involves the relief of the repressed state that is established by
      the unliganded TR/RXR heterodimer during replication-coupled chromatin assembly.
      The association of thyroid hormone with the chromatin-bound TR/RXR heterodimer
      leads to the disruption of local chromatin structure in a transcription
      independent process. Thus, chromatin structure has multiple roles in the
      regulation of TR beta A gene expression in vivo: The TR/RXR heterodimer
      recognizes the response element within chromatin, TR/RXR makes use of the
      chromatin assembly process to silence transcription more efficiently, and TR/RXR
      directs the disruption of local chromatin structure in response to thyroid
      hormone.

PMID- 7590245
TI  - Roles for two RecA homologs in promoting meiotic chromosome synapsis.
AB  - Previous studies have shown that the RAD51 and DMC1 genes of Saccharomyces
      cerevisiae encode homologs of the Escherichia coli RecA strand exchange enzyme.
      Results presented here demonstrate that the dmc1 and rad51 mutants undergo nearly
      complete chromosome synapsis, but synaptonemal complex formation is delayed
      substantially compared with wild type. In the zip1 mutant, chromosomes are paired
      homologously, but not synapsed, and the protein backbones (axial elements) of
      each pair of chromosomes are connected intimately to each other at a few sites
      referred to herein as axial associations. dmc1 zip1 and rad51 zip1 double mutants
      assemble axial elements that are not obviously associated, demonstrating that the
      Dmc1 and Rad51 proteins are required to establish or stabilize axial
      associations. We propose that axial associations serve to promote meiotic
      chromosome synapsis and that the absence of these associations accounts for the
      delayed and inefficient synapsis observed in dmc1 and rad51 strains. During
      meiosis in haploid yeast, chromosome synapsis takes place between nonhomologous
      chromosome segments. In a zip1 haploid, axial associations are not apparent,
      suggesting that these associations depend on interactions between homologous
      sequences.

PMID- 7590247
TI  - Expression of Brca1 is associated with terminal differentiation of ectodermally
      and mesodermally derived tissues in mice.
AB  - We have isolated genomic and cDNA clones of Brca1, a mouse homolog of the
      recently cloned breast cancer-associated gene, BRCA1. Brca1 encodes an 1812-amino
      acid protein with a conserved zinc finger domain and significant homology to the
      human protein. Brca1 maps to Chromosome 11 within a region of conserved synteny
      with human chromosome 17, consistent with the mapping of the human gene to 17q21.
      Brca1 transcripts are expressed in a variety of cultured cells but reveal a
      specific and dynamic expression pattern during embryonic development. For
      example, expression is observed first in the otic vesicle of embryonic day 9.5
      (E9.5) embryos. This expression diminishes and is replaced by expression in the
      neuroectoderm at E10.5. By E11-12.5, higher levels are observed in
      differentiating keratinocytes and in whisker pad primordia. Transcripts also
      become evident in epithelial cells of the E14-17 kidney. Brca1 expression occurs
      in differentiating epithelial cells of several adult organs as well, suggesting a
      general role in the functional maturation of these tissues. Consistent with this,
      Brca1 transcripts are expressed in both alveolar and ductal epithelial cells of
      the mammary gland. During pregnancy, there is a large increase in Brca1 mRNA in
      mammary epithelial cells, an increase that parallels their functional
      differentiation. Because high rates of breast cancer are associated with loss of
      BRCA1 in humans, it is possible that this gene provides an important growth
      regulatory function in mammary epithelial cells. In addition, increased
      transcription of mammary Brca1 during pregnancy might contribute, in part, to the
      reduced cancer risk associated with exposure to pregnancy and lactation.

PMID- 7590248
TI  - Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.

PMID- 7590250
TI  - Human TAFII250 interacts with RAP74: implications for RNA polymerase II
      initiation.
AB  - Accurate and regulated transcription by RNA polymerase II requires the assembly
      of an initiation complex involving multiple protein-DNA and protein-protein
      interactions. A key event is binding of TFIID, a complex consisting of TBP and
      associated factors (TAFs) to the template DNA. The TAF subunits of TFIID carry
      out diverse functions critical for transcription, including specific contact with
      enhancer proteins and binding to core promoter DNA. However, the role of TAFs in
      RNA polymerase II-mediated transcription initiation and cross talk with other
      basal factors remains poorly characterized. Here, we report the specific
      interaction of TAFII250 with RAP74, an essential subunit of the basal
      transcription factor IIF. Using various in vitro binding assays we have mapped
      recognition interfaces between TAFII250 and RAP74. In vivo complementation of a
      temperature-sensitive TAFII250 cell line reveals that the RAP74 interaction is
      critical for cell viability. Because TFIIF is thought to be responsible for
      binding and recruiting RNA polymerase II, the ability of TAFII250 to interact
      selectively with RAP74 is likely to contribute a critical contact for the
      assembly of an active transcription complex.

PMID- 7590249
TI  - Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal
      lethality in I kappa B alpha-deficient mice.
AB  - Transcription factors belonging to the NF-kappa B family are controlled by
      inhibitory I kappa B proteins, mainly I kappa B alpha and I kappa B beta.
      Apparently normal at birth, I kappa B alpha-/- mice exhibit severe runting, skin
      defects, and extensive granulopoiesis postnatally, typically dying by 8 days.
      Hematopoietic tissues from these mice display elevated levels of both nuclear NF
      kappa B and mRNAs of some, but not all, genes thought to be regulated by NF-kappa
      B. NF-kappa B elevation results in these phenotypic abnormalities because mice
      lacking both I kappa B alpha and the p50 subunit of NF-kappa B show a
      dramatically delayed onset of abnormalities. In contrast to hematopoietic cells,
      I kappa B alpha-/- embryonic fibroblasts show minimal constitutive NF-kappa B, as
      well as normal signal-dependent NF-kappa B activation that is concomitant with I
      kappa B beta degradation. Our results indicate that I kappa b beta, but not I
      kappa B alpha, is required for the signal-dependent activation of NF-kappa B in
      fibroblasts. However, I kappa B alpha is required for the postinduction
      repression of NF-kappa B in fibroblasts. These results define distinct roles for
      the two forms of I kappa B and demonstrate the necessity for stringent control of
      NF-kappa B.

PMID- 7590251
TI  - HSF access to heat shock elements in vivo depends critically on promoter
      architecture defined by GAGA factor, TFIID, and RNA polymerase II binding sites.
AB  - Chromatin structure can modulate gene expression by limiting transcription factor
      access to gene promoters. We examined sequence elements of the Drosophila hsp70
      promoter for their ability to facilitate the binding of the transcription factor,
      heat shock factor (HSF), to chromatin. We assayed HSF binding to various
      transgenic heat shock promoters in situ by measuring amounts of fluorescence at
      transgenic loci of polytene chromosomes that were stained with an HSF antibody.
      We found three promoter sequences that influence the access of HSF to its binding
      sites: the GAGA element, sequences surrounding the transcription start site, and
      a region in the leader of hsp70 where RNA polymerase II arrests during early
      elongation. The GAGA element has been shown previously to disrupt nucleosome
      structure. Because the two other critical regions include sequences that are
      required for stable binding of TFIID in vitro, we examined the in vivo occupancy
      of the TATA elements in the transgenic promoters. We found that TATA occupancy
      correlated with HSF binding for some promoters. However, in all cases HSF
      accessibility correlated with the presence of paused RNA polymerase II. We
      propose that a complex promoter architecture is established by multiple
      interdependent factors, including GAGA factor, TFIID, and RNA polymerase II, and
      that this structure is critical for HSF binding in vivo.

PMID- 7590252
TI  - Amino acid substitutions in the structured domains of histones H3 and H4
      partially relieve the requirement of the yeast SWI/SNF complex for transcription.
AB  - Transcription of many yeast genes requires the SWI/SNF regulatory complex. Prior
      studies show that reduced transcription of the HO gene in swi and snf mutants is
      partially relieved by mutations in the SIN1 and SIN2 genes. Here we show that
      SIN2 is identical to HHT1, one of the two genes coding for histone H3, and that
      mutations in either can result in a Sin- phenotype. These mutations are partially
      dominant to wild type and cause amino acid substitutions in three conserved
      positions in the structured domain of histone H3. We have also identified
      partially dominant sin mutations that affect two conserved positions in the
      histone-fold domain of histone H4. Three sin mutations affect surface residues
      proposed to interact with DNA and may reduce affinity of DNA for the histone
      octamer. Two sin mutations affect residues at or near interfaces between (H2A
      H2B) dimer and (H3-H4)2 tetramer subunits of the histone octamer and may affect
      nucleosome stability or conformation. The ability of mutations affecting the
      structure of the histone octamer to relieve the need for SWI and SNF products
      supports the proposal that the SWI/SNF complex stimulates transcription by
      altering chromatin structure and can account for the apparent conservation of SWI
      and SNF proteins in eukaryotes other than yeast.

PMID- 7590253
TI  - CLN3, not positive feedback, determines the timing of CLN2 transcription in
      cycling cells.
AB  - Transcriptional activation of the budding yeast CLN1 and CLN2 genes during the
      late G1 phase of the cell cycle has been attributed to a positive feedback loop,
      wherein the transcription of both genes is stimulated by the accumulation of
      their protein products. We demonstrate that in cycling cells CLN2 does not play a
      role in determining the timing of its own transcriptional activation. First, we
      show that CLN3 alone is sufficient to maximally activate CLN2 transcription.
      Cells that lack functional CLN1 and CLN2 genes activate the CLN2 promoter with
      the same kinetics and at the same size as cells in which all three CLN genes are
      functional. In addition, CLN2 transcription is activated with similar kinetics in
      cells that have CLN2 as their only functional CLN gene and in CLN-deficient
      cells. Promoter analysis shows that CLN3-dependent activation of CLN2
      transcription is directed primarily through the previously identified UAS1 region
      although another cis-acting region, UAS2, also can contribute to CLN2 activation
      under some conditions. The ability to activate transcription of CLN2 is not a
      unique property of CLN3 because ectopically expressed CLN2 can both activate the
      endogenous CLN2 promoter and induce Start. We propose that failure of the
      endogenous CLN2 gene to contribute significantly to activation of its own
      transcription results from its relative effectiveness at inducing Start, cell
      cycle progression and, subsequently, inactivation of CLN2 expression.

PMID- 7590254
TI  - A requirement for bone morphogenetic protein-7 during development of the
      mammalian kidney and eye.
AB  - BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of
      secreted growth factors, is expressed during mouse embryogenesis in a pattern
      suggesting potential roles in a variety of inductive tissue interactions. The
      present study demonstrates that mice lacking BMP-7 display severe defects
      confined to the developing kidney and eye. Surprisingly, the early inductive
      tissue interactions responsible for establishing both organs appear largely
      unaffected. However, the absence of BMP-7 disrupts the subsequent cellular
      interactions required for their continued growth and development. Consequently,
      homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth.
      Overall, these findings identify BMP-7 as an essential signaling molecule during
      mammalian kidney and eye development.

PMID- 7590255
TI  - BMP-7 is an inducer of nephrogenesis, and is also required for eye development
      and skeletal patterning.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional growth factors originally
      identified by their ability to induce ectopic bone formation. To investigate the
      function of one of the BMPs, BMP-7, we have generated BMP-7-deficient mice using
      embryonic stem cell technology. BMP-7-deficient mice die shortly after birth
      because of poor kidney development. Histological analysis of mutant embryos at
      several stages of development revealed that metanephric mesenchymal cells fail to
      differentiate, resulting in a virtual absence of glomerulus in newborn kidneys.
      In situ hybridization analysis showed that the absence of BMP-7 affects the
      expression of molecular markers of nephrogenesis, such as Pax-2 and Wnt-4 between
      12.5 and 14.5 days postcoitum (dpc). This identifies BMP-7 as an inducer of
      nephrogenesis. In addition, BMP-7-deficient mice have eye defects that appear to
      originate during lens induction. Finally, BMP-7-deficient mice also have skeletal
      patterning defects restricted to the rib cage, the skull, and the hindlimbs.

PMID- 7590256
TI  - Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen
      II develop a skeleton with membranous and periosteal bone but no endochondral
      bone.
AB  - Homologous recombination in embryonic stem cells was used to prepare transgenic
      mice with an inactivated Col2a1 gene for collagen II, the major protein component
      of the extracellular matrix of cartilage. Heterozygous mice had a minimal
      phenotype. Homozygous mice developed into fetuses that were delivered vaginally
      but died either just before or shortly after birth. The cartilage in the mice
      consisted of highly disorganized chondrocytes with a complete lack of
      extracellular fibrils discernible by electron microscopy. There was no
      endochondrial bone or epiphyseal growth plate in long bones. However, many
      skeletal structures such as the cranium and ribs were normally developed and
      mineralized. The results demonstrate that a well-organized cartilage matrix is
      required as a primary tissue for development of some components of the vertebrate
      skeleton, but it is not essential for others.

PMID- 7590257
TI  - A protein-RNA interaction network facilitates the template-independent
      cooperative assembly on RNA polymerase of a stable antitermination complex
      containing the lambda N protein.
AB  - The stable association of the N gene transcriptional antiterminator protein of
      bacteriophage lambda with transcribing RNA polymerase requires a nut site
      (boxA+boxB) in the nascent transcript and the Escherichia coli factors NusA,
      NusB, NusG, and ribosomal protein S10. We have used electrophoretic mobility
      shift assays to analyze the assembly of N protein, the E. coli factors, and RNA
      polymerase onto the nut site RNA in the absence of a DNA template. We show that N
      binds boxB RNA and that subsequent association of NusA with the N-nut site
      complex is facilitated by both boxA and boxB. In the presence of N, NusA, and RNA
      polymerase the nut site assembles ribonucleoprotein complexes containing NusB,
      NusG, and S10. The effects on assembly of mutations in boxA, boxB, NusA, and RNA
      polymerase define multiple weak protein-protein and protein-RNA interactions
      (e.g., NusB with NusG; NusA with boxB; NusA, NusB, and NusG with boxA) that
      contribute to the overall stability of the complex. Interaction of each component
      of the complex with two or more other components can explain the many observed
      cooperative binding associations in the DNA-independent assembly of a stable
      antitermination complex on RNA polymerase.

PMID- 7590258
TI  - An in vivo transposase-catalyzed single-stranded DNA circularization reaction.
AB  - Expression of the bacterial insertion sequence IS911 transposase in vivo leads to
      excision and circularization of IS911-based transposons. We show here that
      transposase produces an unusual molecular form generated by single-strand
      cleavage, transfer, and ligation of one end of the element to the opposite end.
      When the transposon is carried by a circular plasmid, this results in the
      formation of a "figure-eight" molecule in which a single strand of the transposon
      is circularized while the corresponding strand of the vector backbone retains a
      single-strand interruption at this position. The results show that a 3' end of
      the transposon is transferred to the opposite target end. Transposase is
      therefore capable of introducing single-strand cleavages at the ends of the
      element, an activity similar to that of retroviral integrases with which it
      shares significant similarities in amino acid sequence. Kinetic studies
      demonstrate that the figure-eight accumulates earlier than transposon circles
      after transposase induction and disappears before circles after inhibition of
      transposase expression, raising the possibility that the figure-eight molecules
      are precursors to the circles. Therefore, IS911 excision as a circle may not
      occur by double-strand cleavage leading to its prior separation from the vector
      backbone in a linear form but could proceed by consecutive circularization of
      each strand.

PMID- 7590260
TI  - bioTk:componentry for genome informatics graphical user interfaces.
AB  - bioTk is a collection of graphical "widgets" and utilities that support
      application programming in the domain of bioinformatics. It is intended to
      establish a framework that encourages the development of communicating window
      based applications and flexible, non-modal user interaction. The current release
      of bioTk has domain-specific widgets for chromosome ideogram displays, genome
      maps, and scrolling sequence windows.

PMID- 7590259
TI  - Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in
      Escherichia coli.
AB  - For a cell to complete DNA replication, every link between the Watson-Crick
      strands must be removed by topoisomerases. Previously, we reported that the
      inhibition of topoisomerase IV (topo IV) leads to the accumulation of catenated
      plasmid replicons to a steady-state level of approximately 10%. Using pulse
      labeling with [3H]thymidine in Escherichia coli, we have found that in the
      absence of topo IV activity, nearly all newly synthesized plasmid DNA is
      catenated. Pulse-chase protocols revealed that catenanes are metabolized even in
      the absence of topo IV and that the residual turnover is carried out by DNA
      gyrase at a rate of approximately 0.01/sec. Using extremely short pulse-labeling
      times, we identified significant amounts of replication catenanes in wild-type
      cells. The rate of catenane unlinking in wild-type cells by the combined
      activities of topo IV and DNA gyrase was approximately 1/sec. Therefore, gyrase
      is 100-fold less efficient than topo IV in plasmid replicon decatenation in vivo.
      This may explain why a fully functional gyrase cannot prevent the catenation of
      newly synthesized plasmid DNA and the partition phenotype of topo IV mutants. We
      conclude that catenanes are kinetic intermediates in DNA replication and that the
      essential role of topo IV is to unlink daughter replicons.

PMID- 7590262
TI  - Association of an unusual form of a Pax7-like gene with increased efficiency of
      skeletal muscle regeneration.
AB  - Efficiency of regeneration of mechanically injured skeletal muscle is more
      pronounced in SJL/J mice, as compared to other laboratory strains in which
      regenerative properties of skeletal muscle are uniformly poor. Previously, we
      postulated that a small number of genes might differ between SJL/J and other
      mouse strains, and would be responsible for this variation in the efficiency of
      skeletal muscle regeneration. The results of initial experiments demonstrated
      that SJL/J mice have a unique form of the myogenic gene, Myo-D1, which partly
      influences efficiency of skeletal muscle repair, and that other genes were also
      involved. To identify other candidate genes, differences were sought within the
      myogenic paired box/homeobox-containing gene Pax7 between SJL/J and other
      laboratory mouse strains. Southern blotting indicated that SJL/J, Quackenbush and
      DDO mice share a Pax7/TaqI RFLP which differs from all other laboratory strains
      tested. This RFLP is most likely due to sequence differences within the homeobox
      of a Pax7-like gene. In vivo studies revealed that Quackenbush and DDO mice also
      share the same regenerative properties of mechanically damaged skeletal muscle as
      SJL/J mice. Since Quackenbush and DDO mice lack the SJL/J type of Myo-D1, and DDO
      belong to a different mouse sub-species, these studies suggest that structural
      alterations in the homeobox of a Pax7-like gene may be implicated in the
      effectiveness of renewal of damaged skeletal muscle of the limb in the mature
      animal.

PMID- 7590261
TI  - Automated construction and graphical presentation of protein blocks from
      unaligned sequences.
AB  - Protein blocks consist of multiply aligned sequence segments that correspond to
      the most highly conserved regions of protein families. Typically, a set of
      related proteins has more than one region in common and their relationship can be
      represented as a series of ungapped blocks separated by unaligned regions.
      Blockmaker is an automated system available by electronic mail
      (blockmaker@howard.fhcrc.org) and the World Wide Web
      (http://www.blocks.fhcrc.org4) that finds blocks in a group of related protein
      sequences submitted by the user. It adapts and extends existing algorithms to
      make them useful to biologists looking for conserved regions in a group of
      related proteins sequences. Two sets of blocks are returned, one in which
      candidate blocks are detected using the MOTIF algorithm and the other using a
      Gibbs sampler algorithm that has been adapted for full automation. This use of
      two block-finding methods based on completely different principles provides a
      'reality check,' whereby a block detected by both methods is considered to be
      correct. Resulting blocks can be displayed using the information-based 'sequence
      logo' method, adapted to incorporate sequence weights, which provides an
      intuitive visual description of both the residue and the conservation information
      at each position. Blocks generated by this system are useful in diverse
      applications, such as searching databases and designing degenerate PCR primers.
      As an example, blocks made from amino acid sequences related to Caenorhabditis
      elegans Tc1 transposase were used to search GenBank, revealing that several fish
      and amphibian genomic sequences harbor previously unreported Tc1 homologs.

PMID- 7590264
TI  - The effects of differential polyadenylation on expression of the dihydrofolate
      reductase-encoding gene in Chinese hamster lung cells.
AB  - Three differently sized mRNAs are expressed from each of two DHFR (encoding
      dihydrofolate reductase) alleles present in the Chinese hamster lung (CHL) cell
      line, DC-3F. The relative abundancy of the transcripts produced from each allele
      differs dramatically as a result of differential utilization of the multiple
      poly(A) sites present in the DHFR DHFR gene and a genetic polymorphism located
      within the third poly(A) signal of one allele. We sought to determine whether
      such differences in polyadenylation affect the steady-state levels of DHFR and
      mRNAs expressed from either allele and, in a more general sense, to ask whether
      differences in 3' end RNA processing in a gene containing multiple poly(A) sites
      affects the final level of gene expression. An SV40 promoter-based transient
      expression system producing chimeric cat::DHFR transcripts was developed to
      regenerate the in vivo mRNA polyadenylation patterns associated with each of the
      two DHFR alleles. The results demonstrate that the total amount of polyadenylated
      RNA expressed from each of these constructs in vitro is the same regardless of
      the differential utilization of the poly(A) signals that occurs between them.
      Moreover, measurement of the individual turnover rates of the DHFR mRNAs
      expressed in vivo from each allele, as determined by pulse-chase labeling and
      actinomycin D inhibition studies, revealed no significant allele-specific
      differences in transcript half-lives. Finally, measuring the steady-state levels
      of DHFR poly(A)+ mRNA in parental DC-3F cells demonstrated that both alleles are
      expressed to the same extent during normal growth. Thus, even though dramatic
      allele-specific differences in 3' end processing of DHFR transcripts occur in
      vivo, such differences do not appear to influence the steady-state levels of DHFR
      gene expression.

PMID- 7590265
TI  - A signal sequence detection system using secreted protease activity as an
      indicator.
AB  - We have developed a novel expression vector, pSSD1, to detect a cDNA fragment
      encoding a secretory signal sequence (Ss). This vector carries a cDNA fragment
      encoding the protease domain of human urokinase-type plasminogen activator (u-PA)
      as a reporter gene under the SV40 early promoter. We inserted cDNA fragments
      encoding various Ss between the promoter and the reporter gene of pSSD1. These
      plasmids were introduced into monkey COS7 cells to produce chimeric proteins.
      Only when the Ss was intact, was fibrinolytic activity detected in the culture
      medium of the transfected cells. Thus, this system may be useful for detecting
      the cDNAs encoding secreted proteins or type-I membrane proteins.

PMID- 7590266
TI  - Different evolutionary behaviour of P element subfamilies: M-type and O-type
      elements in Drosophila bifasciata and D. imaii.
AB  - Distribution and variation of two P-element subfamilies designated M-type and O
      type elements were investigated in Drosophila bifasciata (Db) and its relatives.
      PCR screening revealed that full-sized and internally deleted elements of both
      types occur in three geographic Db strains and in the related species, D. imaii
      (Di). Molecular analyses indicate differences in the evolutionary behaviour of
      the two P-element types. Internally deleted M-type elements fall into two size
      classes present in all three Db strains. In contrast, internally deleted O-type
      elements vary between the strains in number and length. With respect to genomic
      location, M-type elements seem to be restricted to conserved euchromatic sites,
      whereas the positions of O-type elements appear to be geographically variable. In
      one strain of Db (Italy), O-type elements seem to accumulate in the
      heterochromatin. Sequencing of a 397-bp segment shows intra- and interspecific
      divergence of M-type elements. In a 452-bp segment of the O-type elements, no
      substitutions were found, neither within nor between species. This finding
      suggests recent introgression of O-type elements via hybridization between Db and
      Di. Sequence identity and variation in chromosomal locations among different
      copies imply that O-type elements are transpositionally active. For M-type
      elements, genomic mobility cannot be proved. In a survey of several other taxa,
      no O-type-related sequences were detected so far. Therefore, the origin of the O
      type subfamily remains unknown, whereas the source of M-type elements can be
      traced back to the genus Scaptomyza.

PMID- 7590268
TI  - The Drosophila melanogaster homolog of the mammalian MAPK-activated protein
      kinase-2 (MAPKAPK-2) lacks a proline-rich N-terminus.
AB  - Recently, a mammalian kinase cascade was discovered that is triggered by stress
      and heat shock, and leads to the stimulation of mitogen-activated protein kinase
      (MAPK)-activated protein kinase-2 (MAPKAPK-2). Surprisingly, this process turns
      out to be independent of the classical MAPK. The stress-induced activation of
      MAPKAPK-2, in turn, results in the phosphorylation of small heat-shock proteins
      (Hsp). We have isolated a Drosophila melanogaster (Dm) cDNA encoding a
      polypeptide that has extensive sequence similarity to the mammalian MAPKAPK-2. As
      in mammalian MAPKAPK-2, the Dm MAPKAPK-2 possesses a MAPK phosphorylation site
      and a nuclear targeting sequence located C-terminal to the catalytic domain.
      However, in contrast to its mammalian counterpart, it lacks the Pro-rich N
      terminal region proposed to form Src-homology domain 3 (SH3) binding domains. A
      2.4-kb MAPKAPK-2 message is expressed throughout development, while two shorter
      transcripts of 2.3 and 1.8 kb appear to be specifically expressed in the
      germline. The 1.8-kb transcript results from the usage of an atypical germline
      specific polyadenylation signal (AATATA) located early within the 3' untranslated
      region. Dm MAPKAPK-2 is located at cytological position 5D in the Dm genome.

PMID- 7590267
TI  - The Drosophila melanogaster gene lethal(3)73Ah encodes a ring finger protein
      homologous to the oncoproteins MEL-18 and BMI-1.
AB  - The Drosophila melanogaster (Dm) gene lethal(3)73Ah, essential at the late pupal
      stage, encodes a protein with a novel Cys-rich sequence motif, typical for ring
      finger proteins. Amino-acid sequence comparison revealed a striking homology of
      the entire lethal(3)73Ah sequence to the gene products of the mammalian
      oncogenes, mel-18 and bmi-1, and to the zinc-finger-containing N-terminal region
      of the Dm proteins encoded by the Posterior sex combs and Suppressor two of zeste
      genes. The lethal(3)73Ah gene is located in a densely transcribed region sharing
      3'-untranslated sequences with the adjacent sex-determining gene, transformer.
      Its transcription is temporally and spatially regulated with maximal expression
      in adult females. In all stages the mRNA can be localized to the fat body and, in
      addition, to the ovaries of adult females.

PMID- 7590263
TI  - Structure and developmental regulation of the murine ctk gene.
AB  - Csk-type protein tyrosine kinase (Ctk) is a protein tyrosine kinase with
      structural and functional similarities to C-terminal Src kinase (Csk). These
      enzymes catalyze the phosphorylation of C-terminal regulatory tyrosine residues
      of Src family enzymes. Here we describe the structure of the ctk gene and
      characterize the pattern of ctk expression. Ctk and a closely related enzyme,
      nervous tissue and T-lymphocyte kinase (Ntk), are assembled by selective use of
      two of the exons. Expression of ctk was found to be restricted primarily to the
      brain, ctk and csk exhibit a different expression profile in the developing mouse
      brain. The expression of the ctk mRNA and mature polypeptide increase
      postnatally, while the expression of csk decreases with age. Our results thus
      show that despite their structural and functional similarities, ctk and csk
      differ markedly in their patterns of expression.

PMID- 7590270
TI  - Self-cleaving motifs are found in close proximity to the sites utilized for U16
      snoRNA processing.
AB  - A class of small nucleolar RNAs (snoRNAs) is encoded in introns of protein-coding
      genes. The U16 snoRNA belongs to this class; it is encoded in the third intron of
      the Xenopus laevis (Xl) L1 ribosomal protein encoding gene and is released from
      the pre-mRNA by processing both in vivo and in vitro systems. In this paper, we
      show that in close proximity to the U16 snoRNA processing sites, sequences
      displaying self-cleaving activity are present. These elements are conserved in
      the two copies of the Xl L1 and in the single copy of the X. tropicalis L1. The
      catalytic activity corresponds to that already described for the minimal hairpin
      ribozyme [Dange et al., Science 242 (1990) 585-588]; it is Mn(2+)-dependent,
      produces 2'-3' cyclic phosphate and 5'-OH termini and comprises an essential GAAA
      element. Here we show that the 2'-OH group of the G residue is essential for
      catalysis.

PMID- 7590269
TI  - Structure of two cecropin B-encoding genes and bacteria-inducible DNA-binding
      proteins which bind to the 5'-upstream regulatory region in the silkworm, Bombyx
      mori.
AB  - Two genomic DNAs encoding cecropin B (CecB), an antibacterial protein from Bombyx
      mori, were cloned and sequenced. The number of CecB genes was estimated to be
      more than four copies per haploid by genomic Southern blotting. Two genes, CecB1
      and CecB2, were located tandemly within 12 kb in the same orientation. These two
      genes encoded identical amino acids, though 15 nucleotides (nt) were different in
      the coding region and the intron size varied. About 90% of the nt spanning 800 bp
      in the 5'-untranslated region (UTR) were identical between the two genes. This 5'
      flanking region contained characteristic sequences such as a repetitive element
      of B. mori (Bm1), an interleukin-6 response element (IL-6 RE), and two putative
      lipopolysaccharide (LPS) response elements (LPS RE). An electrophoretic mobility
      shift assay (EMSA) showed that the fat body contains at least three different
      nuclear proteins inducible by bacteria which bind to the 5'-UTR, suggesting that
      these proteins may be involved in CecB expression triggered by bacteria.

PMID- 7590272
TI  - Characterization of the murine gene encoding the hyaluronan receptor RHAMM.
AB  - We describe the isolation and characterization of the murine gene encoding RHAMM,
      a hyaluronan receptor which regulates focal adhesion turnover, is required for
      cell locomotion and is a critical downstream regulator of ras transformation. The
      RHAMM gene spans at least 20 kb and comprises 14 exons ranging in size from 75 to
      1099 bp. Primer extension studies indicate that the major transcription start
      point is in position -31, relative to the start Met. Northern blot analysis of
      mouse fibroblast RNA identified two hybridizing species of 4.2 and 1.7 kb.
      Comparison of cDNA clones and RT-PCR products with the genomic clones identified
      alternately spliced exons in both the coding and 5' noncoding regions of RHAMM.
      In the coding region exon 4 is alternately spliced. The major RHAMM transcript
      (RHAMM1) in 3T3 fibroblasts does not contain exon 4 and encodes a protein of 70
      kDa. A minor transcript containing exon 4, namely RHAMM v4, encodes a 73-kDa
      protein, as demonstrated by isoform-specific antibodies. Western analysis
      demonstrated both a major 70-kDa (RHAMM 1) and minor 73-kDa RHAMM protein (v4) in
      3T3 murine fibroblast cell lysates. The functional significance of these two
      isoforms is currently being investigated.

PMID- 7590271
TI  - A H1 histone gene-specific AC-box-related element influences transcription from a
      major chicken H1 promoter.
AB  - In comparing several histone H1 promoters, we have identified a highly conserved
      sequence element, 5'-TGTGTTA, located approx. 450-480 bp upstream from the cap
      site. This TG-box is a near perfect inverted repeat of the previously
      characterized AC-box (5'-AAACACA). The distance between these elements is also
      highly conserved. We performed transient transfection assays with cat gene
      reporter constructs which indicated that both the presence and correct position
      of the TG-box were essential for maximal expression of the chicken 02 H1
      promoter. To the best of our knowledge, this study represents the first
      demonstration of an effect by the TG-box on transcription of a major histone
      encoding H1 gene.

PMID- 7590273
TI  - Cloning of the gene encoding the murine orphan receptor TAK1 and cell-type
      specific expression in testis.
AB  - We have cloned the gene encoding the mouse homologue of the orphan receptor,
      TAK1, a member of the nuclear receptor superfamily, from a mouse testis cDNA
      library. The amino acid sequence of mouse TAK1 (mTAK1) is highly homologous to
      that of human TAK1, with an overall identity of 98%. Northern blot analysis using
      RNA from different testicular cell types showed that the mTAK1 transcript is
      predominantly expressed in pachytene spermatocytes at a low level in round
      spermatids, but not in germ cells at earlier phases of spermatogenesis or in
      Sertoli cells. Southern analysis using genomic DNA prepared from a panel of
      hamster/human and mouse/human hybrid cell lines indicated that the TAK1 gene is
      located on human chromosome 3.

PMID- 7590274
TI  - Rat intestinal crypt-cell replication factor with homology to early S-phase
      proteins required for cell division.
AB  - Cell proliferation requires inhibitory and permissive factors to monitor cell
      cycle progression and control DNA replication. The small intestine has a high
      rate of proliferation and a very low incidence of cancer, suggestive of efficient
      mechanisms for control of the cell cycle and assuring fidelity of DNA
      replication. We have isolated a cDNA from a rat crypt-cell library which
      hybridized to a 3.0-kb mRNA specific for crypt cells, the proliferative cell
      compartment of the intestine. Its amino-acid sequence indicates that it is a new
      member of a family of replication proteins found in yeast, Cenorhabditis elegans,
      mouse and humans. Its transcripts were markedly increased in fetal rat intestine
      and liver, decreased in long-term confluent and serum-starved tissue culture
      cells (IEC cells, a cell line derived from rat crypt cells), increased with serum
      repletion as cells resumed proliferation, and appeared to be species specific.
      Isolation and functional characterization of small intestinal crypt-cell
      replication factors should help explain this organ's low incidence of cancer.

PMID- 7590275
TI  - Cloning of the cDNA encoding rabbit galectin-3.
AB  - The complete coding sequence of the rabbit galectin-3-encoding cDNA (LGALS3) has
      been cloned in a single step by using RT-PCR and specific human LGALS3 cDNA
      primers. The putative protein contains three domains with different degrees of
      homology to other known LGALS3. The homology is high in the C-terminal moiety
      corresponding to the carbohydrate-binding domain and is relatively low in the N
      terminal moiety.

PMID- 7590276
TI  - Cloning and characterisation of the rabbit growth hormone-encoding gene.
AB  - The gene encoding growth hormone (GH) has been cloned from a rabbit genomic
      library, and its sequence has been determined. The rabbit GH gene is similar to
      other mammalian GH, being comprised of five exons and four introns. As in rodents
      and artiodactyls, the rabbit GH occurs as a single gene, with no evidence for a
      cluster of GH-like genes, as is found in primates. The amino acid sequence of
      rabbit GH is similar to that of pig GH and other conserved mammalian GH, and,
      like these, differs markedly from the available sequences of ruminant and primate
      GH. This provides further support for the idea that, in mammals, GH show a slow
      underlying rate of evolution which has increased markedly on at least two
      occasions.

PMID- 7590277
TI  - The porcine follitropin receptor: cDNA cloning, functional expression and
      chromosomal localization of the gene.
AB  - The porcine follitropin receptor-encoding cDNA (pFSHR) was cloned using reverse
      transcription-polymerase chain reaction (RT-PCR). Total RNA from porcine
      granulosa cells was used as template. Two overlapping cDNA fragments encoding,
      respectively, aa 1 to 290 and aa 191 to 694 of the pFSHR were obtained. Taken
      together, the two fragments represented the whole coding sequence, assuming a
      comparable length for the FSHR from the porcine, rat and human species.
      Functionality of the cloned receptor was assessed by expression experiments; COS
      cells transfected with the pFSHR cDNA exhibited high-affinity specific binding
      for [125I]hFSH and FSH-dependent cAMP production. The primary sequence of the
      porcine FSHR N-terminal hormone-binding domain showed high percentages of
      identity with the sequences from ovine, human, and rat origins. A truncated form
      of the pFSHR cDNA, lacking aa 75 to 124 in the N-terminal domain, was also cloned
      and sequenced. A PCR-derived cDNA fragment of 1.45 kb was used as gene-specific
      hybridisation probe to map the pFSHR-encoding gene by radioactive in situ
      hybridization. This gene was found co-localized (as in human) with the porcine
      lutropin hormone receptor (pLHR)-encoding gene on the q2.2-q2.3 region of pig
      chromosome 3.

PMID- 7590278
TI  - Cloning of the cDNA encoding the porcine p55 tumor necrosis factor receptor.
AB  - We have utilized RT-PCR to clone the porcine p55TNFR cDNA, encoding the 55-kDa
      tumor necrosis factor receptor (TNFR), encompassing the entire coding region and
      most of the 3' untranslated region. PCR was performed using total cellular RNA of
      porcine kidney cell line 15 [PK(15)] and primers for the human p55TNFR. Since the
      length of the entire fragment was over 2000 bp, we fused two amplified
      subfragments with the help of a restriction endonuclease. The entire fragment was
      cloned and its amino acid (aa) sequence was compared to the human, rat and mouse
      p55TNFR. This comparison revealed identities of 79, 71 and 72%, respectively. The
      highest identities of 90, 80 and 85% were detected in the so called "death
      domain" for the human, rat and mouse sequences, respectively. This domain is
      crucial for the cytotoxic signal transduction of p55TNFR.

PMID- 7590279
TI  - Cloning and characterization of a cDNA encoding the baboon tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1).
AB  - A baboon aortic smooth muscle cell (SMC) cDNA library was screened for the
      presence of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) by polymerase
      chain reaction (PCR); oligodeoxyribonucleotide primers corresponding to the
      coding frame of the known human TIMP-1 gene were used as primers. Sequencing of
      the PCR-amplified baboon cDNA demonstrated only eight single-nucleotide (nt)
      mismatches, when compared with the coding frame of human TIMP-1. The authenticity
      of the PCR-amplified TIMP-1 cDNA was further confirmed by clonal screening of the
      library with the PCR probe and sequencing of positive clones. On Northern blots
      from cultured baboon SMC, the baboon cDNA hybridized to a TIMP-1-specific mRNA of
      800 bp. Phorbol ester (PMA) treatment of cultured baboon SMC produced a 2.5-fold
      increase in TIMP-1 transcript. TIMP-1 transcripts were also demonstrated in
      cultures of endothelial cells and fibroblasts obtained from baboon arteries.
      Immunohistochemical analysis demonstrated that TIMP-1 protein is localized to the
      adventitial layer of baboon artery. We conclude that TIMP-1 is a conserved
      molecule across species and localized to the tunica adventitia of baboon vessels.

PMID- 7590280
TI  - Sequence diversity and chromosomal distribution of "young" Alu repeats.
AB  - Members of the recently inserted human-specific (HS)/predicted variant (PV)
      subfamily of Alu elements were sequenced. A number of these Alu elements share
      greater than 98% sequence identity with the subfamily consensus sequence, and
      they are flanked by perfect 5' and 3' direct repeats ranging in size from 6 to 15
      nucleotides (nt). Based on the low number of random mutations, the estimated
      average age of these elements was calculated to be 1.5 million years (Myr). All
      the young Alu subfamily members were restricted to the human genome, as judged by
      polymerase chain reaction (PCR) amplification of human and non-human primate DNA
      samples using the unique flanking sequences specific for each Alu element. The
      chromosomal locations of several Alu elements belonging to the young subfamilies,
      designated as HS/PV and Sb2, were determined by PCR amplification of DNA samples
      from human/rodent somatic cell hybrid panels. A statistical analysis of the
      chromosomal distribution pattern showed that the recently inserted Alu elements
      appear to integrate randomly in the human genome.

PMID- 7590281
TI  - Organization of the gene encoding cellular nucleic acid-binding protein.
AB  - The human cellular CNBP gene locus has been sequenced and is comprised of 6453 bp
      from the transcription start point (tsp) to the polyadenylation signal, and an
      additional 201 bp of 5' and 259 bp of 3' flanking sequences. The gene consists of
      five exons, four of which contain coding information for two alternatively
      spliced products, CNPB alpha and beta. The open reading frame (ORF) of 177 amino
      acids (aa) is encoded by exons 2 through 4 (CNBP alpha, M(r) 19463). The protein
      contains seven zinc-finger (Zf) domains. CNBP beta lacks seven aa in the linker
      region between the first two Zf, because of the use of an alternative 5' donor
      site within exon 2. The sixth Zf is the only Zf domain that is not completely
      encoded within a single exon and is interrupted by an intron (intron 4). The 5'
      untranslated region (UTR) contains 849 bp and is interrupted by intron 1. The 3'
      UTR, ending at the polyadenylation signal, is 857 bp long and is contained within
      exon 5. One Alu repeat was identified within intron 1, the largest intron of
      CNBP.

PMID- 7590282
TI  - Role of Ser-53 phosphorylation in the activity of human translation initiation
      factor eIF-4E in mammalian and yeast cells.
AB  - Eukaryotic translation initiation factor eIF-4E is essential for protein
      synthesis and cell viability. eIF-4E participates in formation of an m7GTP-cap
      binding protein complex that mediates association of 40S ribosomal subunits with
      mRNAs, which occurs only when eIF-4E is phosphorylated. Regulation of eIF-4E by
      phosphorylation was thought to occur on Ser53, although results potentially
      inconsistent with phosphorylation of this site have been reported. To resolve
      whether Ser53 is phosphorylated, and if so whether it regulates eIF-4E activity,
      we directly examined whether Ser53 is a site for phosphorylation of mammalian eIF
      4E in human and yeast cells. Wild-type (wt) human eIF-4E protein variants, Ser53-
      >Asp53 or Ser53-->Ala53, were constructed and analyzed by overproduction in
      transfected human 293/T-Ag cells, or in Saccharomyces cerevisiae in which the
      endogenous eIF-4E gene was disrupted. Wt eIF-4E and Ser53 mutants functioned
      equally well in protein synthesis in both systems, and were phosphorylated to the
      same extent. Most importantly, the wt and Ser53 mutants of human eIF-4E produced
      identical tryptic phophopeptide patterns in human cells, and identical but more
      complicated patterns in yeast. These data demonstrate that Ser53 is not a
      requisite activating site for phosphorylation of mammalian eIF-4E in human or
      yeast cells, under conditions in which it participates in protein synthesis.

PMID- 7590283
TI  - Construction and expression of a chimeric gene encoding human terminal
      deoxynucleotidyltransferase and DNA polymerase beta.
AB  - A domain substitution experiment was carried out between the structurally related
      DNA-polymerizing enzymes Pol beta and TdT to investigate the region of Pol beta
      required for template utilization. Site-directed mutagenesis and recombinant DNA
      procedures were used for construction of a gene encoding a chimeric form of the
      two enzymes and termed TDT::POLB, in which the DNA region encoding amino acids
      (aa) 154-212 of TdT was replaced by the corresponding region encoding aa 1-60 of
      POL beta. The construction was confirmed by restriction analysis and DNA
      sequencing. Since this region of POL beta represents most of the N-terminal
      domain of the enzyme possessing single-stranded DNA (ssDNA)-binding activity, it
      was hypothesized that the chimeric protein, unlike TdT, might possess template
      dependent DNA polymerase activity. The chimeric gene product was produced in
      Escherichia coli, purified and subjected to preliminary enzymological
      characterization. The finding that the chimeric TdT::Pol beta protein possessed
      significant template-dependent polymerase activity suggests that aa 1-60 of Pol
      beta are involved in template utilization during the polymerization reaction, as
      suggested by the previous finding that the 8-kDa N-terminal domain of Pol beta
      possesses ssDNA-binding activity [Kumar et al., J. Biol. Chem. 265 (1990a) 2124
      2131; Kumar et al., Biochemistry 29 (1990b) 7156-7159; Prasad et al., J. Biol.
      Chem. 268 (1993) 22746-22755].

PMID- 7590284
TI  - The orphan G-protein-coupled receptor-encoding gene V28 is closely related to
      genes for chemokine receptors and is expressed in lymphoid and neural tissues.
AB  - A polymerase chain reaction (PCR) strategy with degenerate primers was used to
      identify novel G-protein-coupled receptor-encoding genes from human genomic DNA.
      One of the isolated clones, termed V28, showed high sequence similarity to the
      genes encoding human chemokine receptors for monocyte chemoattractant protein 1
      (MCP-1) and macrophage inflammatory protein 1 alpha (MIP-1 alpha)/RANTES, and to
      the rat orphan receptor-encoding gene RBS11. When RNA was analyzed by Northern
      blot, V28 was found to be most highly expressed in neural and lymphoid tissues.
      Myeloid cell lines, particularly THP.1 cells, showed especially high expression
      of V28. We have mapped V28 to human chromosome 3p21-3pter, near the MIP-1
      alpha/RANTES receptor-encoding gene.

PMID- 7590286
TI  - Human peptidylglycine alpha-amidating monooxygenase transcripts derived by
      alternative mRNA splicing of an unreported exon.
AB  - We are characterizing the alternatively spliced human peptidylglycine alpha
      amidating monooxygenase (hPAM)-encoding mRNA transcripts expressed by human
      cells. Reverse transcription coupled to the polymerase chain reaction (RT-PCR)
      has been used to identify four alternatively spliced variants that differ in the
      region joining the two catalytic domains. Two of the transcripts represent
      previously reported splice variants differentiated by the presence (hPAM-A) or
      absence (hPAM-B) of a 321-nucleotide (nt) linker (optional exon A) which in the
      rat produce functionally distinct enzymes. Different mRNAs represent two splice
      variants, hPAM-C and hPAM-D, that show the presence of an exon unreported for PAM
      in any other species. This new exon, designated exon C, is 54 nt in length,
      encodes an 18-amino-acid (aa) peptide containing a conserved dibasic aa
      endoproteolytic processing motif, and is located 3' of exon A in human genomic
      DNA. We propose that cell-specific regulation of mRNA splicing would provide a
      mechanism for control of prohormone activation by these variants of the PAM
      enzyme.

PMID- 7590285
TI  - Isolation of an ubiquitously expressed cDNA encoding human dynamin II, a member
      of the large GTP-binding protein family.
AB  - Dynamin (Dyn) is a member of a novel group of GTPases which was initially
      identified as a microtubule-binding protein with a role in vectorial movement.
      Three distinct Dyn-encoding genes (DYN I, II and III), with a neuronal-,
      ubiquitous or testis-specific expression, respectively, have been identified in
      rat. In man, only DYN I has so far been characterized. We have previously
      isolated a genomic DNA fragment implicated in the correction of mitomycin C
      hypersensitivity of cells from a Fanconi anemia patient belonging to genetic
      complementation group D (FA(D)). Using this probe, we have cloned a human
      complementary DNA designated hDYN II encoding a ubiquitous Dyn isoform. The
      predicted protein consists of 866 amino acids (97.5 kDa). Dyn proteins exhibit a
      high degree of evolutionary conservation: hDyn II is 98% identical to rat Dyn II
      and 73% identical to hDyn I. A unique 3.6-kb transcript is found in all human
      tissues examined and it is more abundant in skeletal muscle and heart. This
      transcript is also expressed in tissue-culture cells. The hDYN II message is
      present and not mutated in the FA(D) patient studied. In addition to the GTP
      binding domain and motifs associated with regulatory function, the hDyn II
      protein contains a noticeable number of concensus motifs for p34Cdc2 kinase
      phosphorylation which may indicate a potential role at the G2/mitosis transition.
      The sequence reported here should allow a more complete analysis of Dyn
      function(s) in man.

PMID- 7590287
TI  - Cloning and functional expression of a human gene, hIRK1, encoding the heart
      inward rectifier K+-channel.
AB  - We have isolated a cDNA clone encoding a human inward rectifier potassium channel
      (hIRK1). The nucleotide (nt) sequence of the coding region is 88% similar to the
      mouse clone with only seven amino-acid (aa) differences. The hIRK1 cRNA initially
      expressed low levels of protein in a wheat germ system and in Xenopus oocytes.
      The addition of a SmaI site 3' to the poly(A) tail increased the expression at
      least tenfold. Xenopus oocytes injected with the hIRK1 cRNA developed resting
      potentials that averaged -96 mV and a large inward current that was blocked by
      Ba2+ or Cs+. The hIRK1 EK shifted 54.6 mV per decade change in [K]o, and its
      channel conductance increased with [K]o by a 0.3 exponent factor. Above EK, the
      hIRK1 I-V relation has a distinct 'N'-shape. Cell-attached single-channel
      conductance in 140 mM K+ pipette solution averaged 29 pS. The negative resting
      potential and the 'N'-shape I-V relation of hIRK1 closely resemble that of the
      native cardiac inward rectifier IK1.

PMID- 7590289
TI  - Characterization of a cDNA clone encoding E2-20K, a murine ubiquitin-conjugating
      enzyme.
AB  - The 20-kDa ubiquitin-conjugating enzyme E2-20K is induced specifically during a
      late stage of erythroid differentiation. Here we report the sequence of a murine
      cDNA encoding E2-20K. Northern blot analysis identified polyadenylated
      transcripts of 3.5 and 6.5 kb which are present at comparable levels in many
      nonerythroid tissues.

PMID- 7590290
TI  - Cloning of the gene encoding the mouse homologue of the human calcium signal
      modulating ligand.
AB  - A cDNA clone, representing the mouse homologue of the recently described gene
      encoding the human calcium signal-modulating ligand, was isolated from a mouse
      thymus library. This clone exhibits extensive conservation of the primary
      nucleotide and deduced amino-acid sequences that, when considered with a similar
      secondary protein structure, transcript size and distribution of expression,
      suggests a similarity in function.

PMID- 7590291
TI  - Sequence of the rabbit glyceraldehyde-3-phosphate dehydrogenase-encoding cDNA.
AB  - Two full-length cDNA clones encoding rabbit glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) were isolated from a lambda gt10 rabbit spleen cDNA library
      and sequenced. As predicted from the open reading frame (ORF) in vitro
      translation of a sense orientation GAPDH cDNA clone yielded a protein product
      with a molecular mass of 37 kDa. Rabbit GAPDH exhibits a high degree of homology
      to the mouse, rat, hamster, chicken and human GAPDH on both the nucleotide (nt)
      and amino acid (aa) levels.

PMID- 7590292
TI  - Cloning and characterization of a cDNA encoding the specific phosphatidylcholine
      transfer protein from bovine liver.
AB  - A 1917-bp cDNA clone encoding phosphatidylcholine transfer protein (PC-TP) was
      identified by screening a bovine liver library. Northern blot analysis
      demonstrated a 2-kb mRNA transcript in bovine liver, and Southern blotting was
      consistent with a single bovine PC-TP gene which was shown to be present in a
      diverse group of vertebrates, but not in yeast. Database comparisons revealed the
      nucleotide sequence of the clone to be unique and unrelated to other cytosolic
      lipid TP.

PMID- 7590293
TI  - Identification and cloning of the G3B cDNA encoding a 3' segment of a protein
      binding to GATA-3.
AB  - The transcription factor GATA-3 contributes to the expression of several genes
      critical for T-cell function and development, including the T-cell receptor alpha
      and beta chains. We report here the isolation of a human cDNA clone which encodes
      a 3' segment of a novel protein with three zinc fingers. This protein, which we
      termed G3B, can interact with GATA-3 in vitro. Its mRNA is expressed in T and B
      cells. Thus, G3B may represent a potential regulator of GATA-3 function.

PMID- 7590288
TI  - Cloning of a cDNA encoding the S13 ribosomal protein from the catfish Ictalurus
      punctatus.
AB  - A cDNA clone (rpS13) encoding the S13 ribosomal protein (rpS13) has been isolated
      from the catfish Ictalurus punctatus, and is the first example of an rpS13
      isolated from a teleost species. The deduced 151-amino-acid (aa) sequence is 96%
      identical to the rat and human rpS13, extending the evolutionary conservation of
      this protein.

PMID- 7590294
TI  - Sequence of the 5' regulatory domain of the gene encoding the rat beta 2
      adrenergic receptor.
AB  - Restriction mapping and sequence analysis of the gene encoding the rat beta 2
      adrenergic receptor (beta 2AR) revealed an error affecting most of the 5'
      flanking domain, located between -192 and -2245 bp in the only published sequence
      of this gene [Buckland et al., Nucleic Acids Res. 18 (1990) 682]. The correct
      sequence lacks a TATA box, contains 67% G + C residues in the first 500
      nucleotides upstream from the start codon, and contains putative glucocorticoid,
      thyroid hormone and cAMP-response elements.

PMID- 7590297
TI  - The nodD locus from Azorhizobium caulinodans is flanked by two repetitive
      elements.
AB  - The sequence surrounding the Azorhizobium caulinodans (Ac) regulatory nodD gene
      was analyzed. Upstream from nodD and in the opposite orientation, two small open
      reading frames were identified (ORF1 and ORF2). The DNA sequence corresponding to
      ORF1, termed epsilon 1, is similar to a part of the insertion element IS51 from
      Pseudomonas savastanoi. Immediately downstream from nodD, a repeated element,
      delta 1, has been described [Goethals et al., Mol. Plant-Microbe Interact. 5
      (1992) 405-411]. The elements epsilon 1 and delta 1 form the borders of a shift
      in GC content between nodD and its surrounding sequences. delta 1 and the
      ORF1+ORF2 sequence both occur as two copies in the Ac genome. Based on these
      observations, we postulate that the repeated elements played a role in the
      horizontal transfer of nodD during evolution. Insertion mutations in epsilon 1
      and delta 1 did not influence the induction of the nodulation operon, nodABCSUIJ,
      and had no effect on the nodulation behavior on Sesbania rostrata. lacZ fusion
      studies suggested that nodD is constitutively transcribed and that the promoter
      driving nodD expression overlaps with the ORF1 sequence. In contrast, promoter
      activity in the direction of ORF1 and ORF2 was not observed. In the nodD-ORF1
      intervening sequence, a nod box-related motif was recognized that deviates from
      active nod boxes by the absence of an ATC-9-bp-GAT palindrome, i.e., a sequence
      involved in NodD-mediated transcription stimulation [Goethals et al., Proc. Natl.
      Acad. Sci. USA 89 (1992) 1646-1650].

PMID- 7590296
TI  - Complete sequences and organization of the rrnA operon from campylobacter jejuni
      TGH9011 (ATCC43431).
AB  - The rrnA ribosomal RNA (rRNA) operon of Campylobacter jejuni (Cj) TGH9011
      (ATCC43431) was cloned and sequenced to completion. rRNAs were then characterized
      by primer extension and S1 nuclease mapping analysis. The secondary structure
      models of Cj 16S and 23S rRNAs were constructed, and the models were compared to
      the corresponding models from other eubacterial rRNA. The analysis presented a
      typical 5'-promoter-16S-tRNAs-23S-5S-terminator-3' prokaryotic rRNA operon
      structure. However, an unusual organization of the intercistronic tRNAs was
      observed where the two tRNAs, tRNA(Ala) and tRNA(Ile), were present in the order
      5'-16S-tRNA(Ala)-tRNA(Ile)-23S-3', which is opposite of the typical 5'-16S
      tRNA(Ile)-tRNA(Ala)-23S-3' structure observed in other bacteria.

PMID- 7590295
TI  - Buffer composition mediates a switch between cooperative and independent binding
      of an initiator protein to DNA.
AB  - The regulation of many biological processes, including DNA replication, is
      frequently achieved by protein-protein interactions, as well as protein-DNA
      interactions. Multiple protein-binding sites are often involved. For example, the
      replication of plasmid R6K involves binding of the initiator protein pi to seven
      22-bp direct repeats (DR) in the gamma origin of replication (gamma ori). A
      mutant protein pi S87N has been isolated, that in Tris.borate buffer (TB) binds
      cooperatively to seven DR, whereas wild-type (wt) pi binds independently
      [Filutowicz et al., Nucleic Acids Res. 22 (1994) 4211-4215]. Surprisingly, we
      found that wt pi can also bind cooperatively when Tris.acetate (TA),
      Tris.succinate or Tris.glutamate buffers are used instead of TB. The cooperative
      binding of the wt pi protein was also observed in the TB buffer at high
      concentrations of Na2EDTA. These results suggest that pi may be able to assume
      two functionally distinct conformations as a result of either mutation or buffer
      composition. Moreover, we found that the mode of pi binding is determined not by
      the composition of the buffer in which the reaction was assembled, but by the
      composition of the electrophoresis buffer. We discuss the general implications of
      these findings.

PMID- 7590298
TI  - The Bacillus subtilis cell-division 135-137 degrees region contains an essential
      orf with significant similarity to murB and a dispensable sbp gene.
AB  - Sequence similarity analysis has revealed that orf2, in the cell division 135-137
      degrees region of the Bacillus subtilis (Bs) chromosome, is the probable homolog
      of Escherichia coli murB (encoding a reductase involved in peptidoglycan
      synthesis). The amino-acid sequences of the two protein products show 24%
      identity (47% overall similarity), with several regions of higher similarity
      which may represent functional domains of the proteins. Attempts to insertionally
      inactivate orf2 were unsuccessful, strongly suggesting that it is an essential Bs
      gene. A small gene found in the same region as orf2, sbp (encoding the 'small
      basic protein'), was shown to be non-essential in Bs.

PMID- 7590300
TI  - Construction and evaluation of new drug-resistance cassettes for gene disruption
      mutagenesis in Streptococcus pneumoniae, using an ami test platform.
AB  - Although drug-resistance markers have been used frequently for gene-disruption
      mutagenesis in Streptococcus pneumoniae, none has yet been shown to be free of
      dependence on local transcription for its expression. Indeed, the erythromycin
      resistance marker (erm), originating in pAM beta 1, has been used as an indicator
      of local transcription on several occasions. A procedure is demonstrated for
      evaluation of the autonomous expression of such a marker by placing it in a
      consistent background, at the pneumococcal ami (aminopterin resistance) locus, in
      combination with active or inactive alleles of the ami promotor (pA). Using this
      test platform, a chloramphenicol-resistance marker (cat) and a spectinomycin
      resistance marker used in streptococcal gene disruption studies and derived from
      pJS3 and pDL269, respectively, were shown to depend on local transcriptional
      signals for expression when placed in the pneumococcal chromosome as single-copy
      genes. To overcome this limitation, new drug-resistance cassettes were designed
      and constructed, using pA as a model for synthetic promoters for the erm and cat
      genes. Both new cassettes were shown, by the same procedure, to be expressed
      after insertion in the pneumococcal chromosome, independent of local
      transcription. A new insertion-duplication vector, pEVP3, incorporating the new
      cat cassette and a lacZ reporter derived from pTV32, was also constructed. The
      ami test platform was used to demonstrate both the autonomous expression of cat
      and the reporter function of lacZ in chromosomal copies of pEVP3.

PMID- 7590299
TI  - Sequence and expression of the bpdC1C2BADE genes involved in the initial steps of
      biphenyl/chlorobiphenyl degradation by Rhodococcus sp. M5.
AB  - The nucleotide (nt) sequence of the bpdC1C2BADE genes which encode the first
      three enzymes in the biphenyl (BP) degradation pathway of Gram+ Rhodococcus sp.
      M5 (formerly Arthrobacter M5) was determined. Except for the ferredoxin component
      (BpdB) of the initial BP dioxygenase, the predicted amino acid (aa) sequences of
      the remaining proteins are found to be more closely related to the counterpart
      proteins (TodC1C2BADE) present in the toluene-degrader, Pseudomonas putida F1,
      than those of three BP-degrading pseudomonads. The cloned bpd genes were verified
      by their expression in the Escherichia coli T7 RNA polymerase/promoter system. In
      E. coli, BpdA was able to complement TodC1C2B in indigo biosynthesis, although
      the M5 native or cloned BP dioxygenase does not carry out this reaction.

PMID- 7590301
TI  - Production of the 19-kDa antigen of Mycobacterium tuberculosis in Escherichia
      coli and its purification.
AB  - The 19-kDa antigen (19Ag) of Mycobacterium tuberculosis (Mt) is a lipoprotein
      which is released from the organism during growth. In order to study the possible
      involvement of this antigen in the host protective response against Mt infection,
      it would be helpful to obtain high-level production of 19Ag from a recombinant
      organism. We have found that overexpression of the native 19Ag gene in
      Escherichia coli or yeast leads to products which are aggregated and insoluble.
      By site-directed mutagenesis of the 19Ag lipoprotein leader sequence, we have
      generated a mutant gene which directs the production of 19Ag into the periplasmic
      space of E. coli, from where it can be easily purified in high yield. 19Ag
      obtained from this mutant construct lacks the lipid-modified N-terminal Cys
      residue found in the native 19Ag, and is not glycosylated, but is otherwise
      indistinguishable from 19Ag isolated from Mt culture supernatant.

PMID- 7590302
TI  - Cloning and sequence analysis of the gene encoding the DNA polymerase I from
      Mycobacterium tuberculosis.
AB  - The polA gene (encoding DNA polymerase I) from Mycobacterium tuberculosis was
      cloned using an internal gene segment probe generated by PCR amplification of
      genomic DNA [Mizrahi et al., Gene 136 (1993) 287-290]. The gene encodes a
      polypeptide 904 amino acids (aa) in length that shares 89% identity with a 911-aa
      homologue from Mycobacterium leprae. The polypeptide has all of the primary
      structural elements necessary for DNA polymerase and 5'-3' exonuclease activity,
      but lacks the motifs required for an associated 3'-5' exonuclease (proofreading)
      activity.

PMID- 7590304
TI  - Isolation, sequencing and expression of the superoxide dismutase-encoding gene
      (sod) of Nocardia asteroides strain GUH-2.
AB  - Nocardia asteroides (Na) superoxide dismutase (SOD) has been implicated as a
      virulence factor that allows the organism to survive intracellular killing by
      phagocytic cells. A full-length Na sod gene from a pathogenic strain of Na
      (strain GUH-2) was cloned from a recombinant phage library using the
      Mycobacterium tuberculosis (Mt) sod gene (Mt sod) as a probe. The promoter region
      and structural gene (624 bp) of Na sod was sequenced and nucleotide sequence
      comparisons reveal 77% homology with Mt sod. The Na sod gene also shares
      considerable sequence homology with sod of other mycobacterial species. In
      addition, conserved amino acid (aa) sequences important for metal binding
      indicate that Mn2+ is the preferred metal ion ligand for Na SOD. An Na sod
      expression plasmid, pYEX1, under transcriptional control of the Mt hsp70 promoter
      (pY6013), produced a 25-kDa protein product which showed SOD activity when
      stained in a native polyacrylamide gel and reacted with rabbit polyclonal
      antibody specific for Na SOD by Western blot. pYEX1, via transformation, was able
      to complement an Escherichia coli double sodAB mutant deficient in SOD production
      in the presence of paraquat (methyl viologen) which stimulates the production of
      superoxide radicals.

PMID- 7590303
TI  - The thiostrepton-resistance-encoding gene in Streptomyces laurentii is located
      within a cluster of ribosomal protein operons.
AB  - A common approach to identify and clone biosynthetic gene from an antibiotic
      producing streptomycete is to clone the resistance gene for the antibiotic of
      interest and then use that gene to clone DNA that is linked to it. As a first
      step toward cloning the genes responsible for the biosynthesis of thiostrepton
      (Th) in Streptomyces laurentii (Sl), the Th resistance-encoding gene (tsnR) was
      cloned as a 1.5-kb BamHI-PvuII fragment in Escherichia coli (Ec), and shown to
      confer Th resistance when introduced into S. lividans TK24. The tsnR-containing
      DNA fragment was used as a probe to isolate clones from cosmid libraries of DNA
      in the Ec cosmid vector SuperCos, and pOJ446 (an Ec/streptomycete) cosmid vector.
      Sequence and genetic analysis of the DNA flanking the tsnR indicates that the Sl
      tsnR is not closely linked to biosynthetic genes. Instead it is located within a
      cluster of ribosomal protein operons.

PMID- 7590305
TI  - Analysis of the DnaK molecular chaperone system of Francisella tularensis.
AB  - We have cloned the Francisella tularensis (Ft) grpE-dnaK-dnaJ heat-shock genes
      which are organized in that order. These genes allow heterologous genetic
      complementation of each respective mutant strain of Escherichia coli (Ec) for
      bacteriophage lambda growth. The nucleotide sequences of the Ft grpE-dnaK-dnaJ
      genes and the deduced amino-acid sequences share significant homologies with
      their respective Ec counterparts. The Ft DnaK and DnaJ proteins cross-react with
      polyclonal antibodies raised against the respective Ec proteins. The grpE-dnaK
      dnaJ genes of Ft are organized in a fashion that is more characteristic of Gram+
      bacteria.

PMID- 7590306
TI  - Aspartyl-tRNA synthetase of the hyperthermophilic archaeon Pyrococcus sp. KOD1
      has a chimerical structure of eukaryotic and bacterial enzymes.
AB  - The aspartyl-tRNA synthetase (AspRS)-encoding gene from the archaeon, Pyrococcus
      sp. KOD1 (KOD1), was cloned and sequenced, and expressed in Escherichia coli. The
      purified AspRS possessed an aminoacyation activity for tRNA extracted from KOD1.
      Analysis of the deduced amino-acid sequence (438 aa, 50,893 Da) revealed that the
      AspRS of KOD1 is a chimerical protein of bacteria and eukarya. Regional analysis
      showed high sequence similarity to higher eukaryotic enzymes in the central and C
      terminal regions which are important for catalytic activity of the enzyme. In
      contrast, the N-terminal portion exhibits bacterial features and does not possess
      the higher eukaryotic sequence which is involved in high molecular weight (HMW)
      complex formation. These results suggest that archaeon AspRS has a eukaryotic
      type catalytic mechanism without forming the HMW complex. This is the first
      example which shows that an archaeal protein possesses eukaryotic and bacterial
      features.

PMID- 7590308
TI  - Sequence, codon usage and cysteine periodicity of the SerH1 gene and in the
      encoded surface protein of Tetrahymena thermophila.
AB  - The temperature-regulated SerH1 gene coding for an immunodominant surface
      glycoprotein (i-Ag H1) of Tetrahymena thermophila has been sequenced. The gene is
      reproducibly rearranged during macronuclear development and steady state mRNA
      levels are present at < 36 degrees C. The deduced i-Ag H1 amino acid (aa)
      sequence is rich in Ser, Thr and Cys, and contains three periods each consisting
      of 85 aa punctuated by eight Cys with the general formula,
      CX6CX17CX2CX18CX2CX11CX2CX19 (where X = any aa). Such Cys periodicity is common
      to ciliate i-Ag. Codon usage in Tt, Paramecium primaurelia and P. tetraurelia i
      Ag encoding genes is similar, with approx. 80% A+T in the 3' position which is in
      marked contrast to the approx. 54% 3' A+T in other ciliate genes.

PMID- 7590307
TI  - The SPR3 gene encodes a sporulation-specific homologue of the yeast CDC3/10/11/12
      family of bud neck microfilaments and is regulated by ABFI.
AB  - The SPR3 gene is selectively activated only during the sporulation phase of the
      Saccharomyces cerevisiae (Sc) life cycle. The predicted amino acid (aa) sequence
      has homology to microfilament proteins that are involved in cytokinesis and other
      proteins of unknown function. These include the products of Sc cell division
      cycle (CDC) genes involved in bud formation (Cdc3p, Cdc10p, Cdc11p and Cdc12p),
      Candida albicans proteins that accumulate in the hyphal phase (CaCdc3p and
      CaCdc10p), mouse brain-specific (H5p) and lymphocyte (Diff6p) proteins,
      Drosophila melanogaster (Dm) protein Pnutp (which is localized to the cleavage
      furrow of dividing cells), a Diff6p homologue (DmDiff6p), and the Sc septin
      protein (Sep1hp), a homologue of the 10-nm filament proteins of Sc. One strongly
      conserved region contains a potential ATP-GTP-binding domain. Primer extension
      analysis revealed six major transcription start points (tsp) beginning at -142
      relative to the ATG start codon. The sequence immediately upstream from the tsp
      contains consensus binding sites for the HAP2/3/4 and ABFI transcription factors,
      a T-rich sequence and two putative novel elements for mid to late sporulation,
      termed SPR3 and PAL. Electrophoretic mobility shift assay (EMSA) and footprint
      analyses demonstrated that the ABFI protein binds to a region containing the
      putative ABFI site in vitro, and site-directed mutagenesis showed that the ABFI
      motif is essential for expression of SPR3 at the appropriate stage in sporulating
      cells.

PMID- 7590309
TI  - STT3, a novel essential gene related to the PKC1/STT1 protein kinase pathway, is
      involved in protein glycosylation in yeast.
AB  - Mutations of genes involved in the STT1/PKC1 pathway in yeast show staurosporine
      and temperature sensitivities (stt) which are suppressed by the addition of 1 M
      sorbitol [Yoshida et al., Mol. Gen. Genet. 242 (1994) 631-640]. Among the stt
      mutants, stt3-2 shares this phenotype. The STT3 gene encodes a novel 718-amino
      acid protein with significant homology to potential transmembrane proteins of
      Caenorhabditis elegans and mouse mandibular condyle (about 80% homologous and 60%
      identical). Unlike the STT1/PKC1 gene, STT3 is essential for cell growth
      irrespective of osmotic support. Pulse-chase experiments show that the sst3
      mutants are defective in protein glycosylation. The stt3 mutants are sensitive to
      hygromycin B and resistant to sodium orthovanadate, whose phenotypes are common
      to those defective in protein glycosylation.

PMID- 7590310
TI  - Sequence and analysis of the O antigen gene (rfb) cluster of Escherichia coli
      O111.
AB  - The O antigens found in Salmonella enterica (Se) and Escherichia coli (Ec) show a
      great deal of diversity, and only three structures are known to be common to both
      genera. Two of them contain the 3,6-dideoxyheoxse colitose, not found in other
      serogroups of the two species. The first of these is common to Ec O111 and Se
      O:35 (sv Adelaide); the other is found in both Ec O55 and Se O:50 (sv Greenside).
      The genes specific for the synthesis of O antigen are generally located in the
      rfb gene cluster at map position 45 min in Ec and 42 min in Se. The rfb (O
      antigen) gene cluster of an Ec O111 strain M92 had been cloned earlier and
      hybridisation analysis suggested that the rfb clusters of Ec M92 and a Se sv
      Adelaide strain had been acquired separately by the two species since their
      divergence. We have now sequenced part of the rfb cluster from Ec M92. We
      identify two genes of the GDP-colitose pathway, rfbM and rfbK, and show that
      several other ORFs have similarity to the rfb and cps (capsular polysaccharide)
      genes. Downstream of this block of genes is an ORF which encodes a protein with
      predicted transmembrane segments which is presumed to correspond to the rfbX
      gene. The % G+C values of the Ec M92 rfb sequence are extremely low, indicating
      that the rfb evolved in a low % G+C species of bacteria before transfer into Ec.

PMID- 7590311
TI  - pDblet, a stable autonomously replicating shuttle vector for Schizosaccharomyces
      pombe.
AB  - We have constructed a new multipurpose stable shuttle vector for the fission
      yeast Schizosaccharomyces pombe (Sp). Plasmid pDblet was designed to provide
      convenient features for molecular work and to overcome the inconveniences of
      previously designed Sp vectors. It contains the Sp ura4 gene as selectable marker
      and a new highly efficient ARS (autonomously replicating sequence) element,
      allowing the vector to remain stable as a monomer in Sp. In addition, pDblet
      transforms Sp with high efficiency and has high mitotic stability and low copy
      number.

PMID- 7590312
TI  - Increase in mRNA of multiple Eh pgp genes encoding P-glycoprotein homologues in
      emetine-resistant Entamoeba histolytica parasites.
AB  - With the goal of understanding possible mechanisms of drug resistance by the
      protozoan parasite Entamoeba histolytica (Eh), two novel Eh P-glycoprotein (Pgp)
      genes (Eh pgp5 and Eh pgp6) were sequenced, and the expression of four Eh pgp
      genes determined in wild-type (wt) clone A and emetine-resistant (EmR) clone C2
      amebae. The Eh pgp5 gene encodes a 1301-amino acid (aa) protein that is similar
      to those of Eh pgp1 (64% aa identity), Eh pgp2 (61%), Eh pgp6 (39%) and Homo
      sapiens MDR (multidrug-resistance-encoding)(Hs MDR1; 38%) genes. The 1282-aa Eh
      pgp6 open reading frame (ORF), which is 19-28 aa shorter than those encoded by
      other Eh pgp, is also similar to those of Eh pgp1 (46% aa identity), Eh pgp2
      (38%), and Hs MDR1 (39%). Both Eh pgp5 and Eh pgp6 ORF predict two ATP-binding
      cassettes and twelve hydrophobic alpha-helices, which form the putative
      transmembrane channel. EmR clone C2 amebae, growing at all concentrations of
      drug, show increased amounts of Eh pgp1 and Eh pgp6 mRNA when compared to wt
      clone A amebae. In contrast, only clone C2 amebae selected for growth at the
      highest concentrations of emetine (100-200 micrograms/ml) show increased Eh pgp5
      mRNA, while mRNA of both clone C2 and clone A Eh amebae fail to bind an Eh pgp2
      specific probe. It appears then that multiple Pgp may contribute to amebic Em
      resistance in vitro.

PMID- 7590313
TI  - Construction of a recombinant cellulolytic Escherichia coli.
AB  - A 1.2-kb DNA fragment from Bacillus subtilis CD4 encoding endo-beta-1,4-glucanase
      and cellobiase activities was cloned and expressed in Escherichia coli.
      Carboxymethylcellulase (CMCase) and cellobiase activities were detected in a cell
      free lysate of recombinant (re-) E. coli (Ec). The re-enzymes were functional in
      Ec, as it utilized carboxymethylcellulose, soluble cellulose and cellobiose as
      sole carbon sources for growth.

PMID- 7590314
TI  - Sequence of a gene encoding periplasmic Pseudomonas syringae ankyrin.
AB  - A gene encoding ankyrin (Ank) was isolated from a genomic library of the plant
      pathogen Pseudomonas syringae pathovar syringae strain 61 (Pss61). The gene
      encodes an 183-amino-acid (aa) polypeptide which has homology to the 33-aa repeat
      domain of mammalian Ank and Ank homologs from other bacteria, animals and plants.

PMID- 7590315
TI  - Sequence analysis, distribution and expression of an aminopeptidase N-encoding
      gene from Lactobacillus helveticus CNRZ32 [gene 155 (1995) 89-93].
AB  - Lactobacillus (Lb.) helveticus CNRZ32 possesses a 97-kDa metalloenzyme with
      aminopeptidase activity (PepN; EC 3.4.11.2). A 3.8-kb fragment encoding PepN was
      cloned into pIL253 and designated pSUW34. Transformation of Lactococcus (Lc.)
      lactis LM0230 with pSUW34 resulted in > 180-fold increase in general
      aminopeptidase (AP) activity using L-lysine-p-nitroanilide. Southern
      hybridization was conducted to determine the distribution of homology to the
      CNRZ32 pepN gene among lactic-acid bacteria (LAB). Hybridization was observed
      with strains of lactobacilli, pediococci, leuconostoc, streptococci and
      lactococci. The pepN gene was sequenced and found to encode a protein containing
      844 amino acid (aa) residues. A comparison of Lb. helveticus CNRZ32 pepN to Lb.
      delbrueckii ssp. lactis DSM7290 pepN indicated 69.5% nucleotide (nt) identity and
      71.8% aa identity, while comparison to pepN from Lc. lactis ssp. cremoris MG1363
      indicated 61.1% nt identity and 49.2% aa identity. Alignment of peptidase aa
      sequences of LAB, Escherichia coli, yeast and mammalian origin display homology
      in the zinc-binding domain, as well as a conserved region upstream from the
      putative active site.

PMID- 7590316
TI  - Cloning and transcription regulation of the ferric uptake regulatory gene of
      Campylobacter jejuni TGH9011.
AB  - A Campylobacter jejuni (Cj) TGH9011 (ATCC 43431) gene homologous to the
      Escherichia coli ferric uptake regulatory gene (fur) has been cloned and
      characterized. Cj fur encodes a polypeptide consisting of 157 amino acids (aa)
      (18.1 kDa). The 5'-flanking region of the Cj fur gene contains two putative
      catabolite activator protein (CAP)-binding sequences and four Fur boxes or Fur
      binding sequences (FBS), implicating cAMP and autogenous regulation respectively.
      A major and a minor transcription start point (tsp) were active in Fe(+) and Fe(
      ) media and three tsp were suppressed in Fe(+) condition. The major transcript
      has an unusually short leader sequence. The homology of the Cj Fur to other
      Proteobacteria Fur proteins is moderately low with identity ranging from 36.3%
      for Yersinia pestis to 31.8% for Legionella pneumophila. Multiple alignments of
      the Fur sequences identified three conserved motifs, I [aGLKvTlpR1KiL], II
      [eiGlATvYR] and III [HHDHlvCldcGeviEf] (uppercase aa are identical in 12 or all
      13 Fur sequences and lowercase aa are identical in six or more sequences). A
      truncated TGFH9011 Fur missing 18 aa of the N terminus but retaining all three
      conserved motifs was shown to bind all four FBS sequences. The binding and
      transcription studies support autoregulation of fur expression in Cj.

PMID- 7590317
TI  - A method of directed random mutagenesis of the yeast chromosome shows that the
      iso-1-cytochrome c heme ligand His18 is essential.
AB  - A method to perform site-directed random mutagenesis directly in the yeast
      chromosomal DNA at the iso-1-cytochrome c-encoding gene locus (CYC1) is
      described. To test the effectiveness of the random mutagenesis procedure, the
      heme ligand His18 was mutated to Ala (H18A), rendering cytochrome c (Cyc)
      nonfunctional. Random mutagenesis was performed by transforming yeast cells with
      a synthetic oligodeoxyribonucleotide (oligo) that randomizes the codon for His18.
      The transformed cells were then selected for reversion to a functional Cyc on
      selective media. Ten functional mutants were recovered, all of which had
      integrated the synthetic oligo. Sequencing showed that five of the recovered
      mutants carried the His codon, CAU, and five mutants contained the His codon,
      CAC. Because Arg had previously been found as a heme ligand, this mutant was
      produced by standard techniques and integrated into the yeast chromosome. These
      yeast did not produce a holo cytochrome c that was detectable by low-temperature
      spectroscopy. To develop a selection for nonfunctional Cyc, competent yeast
      (which lack the ability to synthesize tryptophan) were cotransformed with a
      plasmid carrying the TRP1 gene and the random oligo, and were plated on media
      lacking tryptophan. Of the 1200 colonies that grew, 120 tested negative for the
      integration of the random oligo, demonstrating that this particular selection for
      nonfunctional protein is not feasible. A method is thus described for directed,
      random mutagenesis directly in the yeast chromosome that can be used to probe
      structure/function relationships in Cyc. Only His can act as a heme ligand at
      position 18, using the functional selection described here.

PMID- 7590318
TI  - Detection of exonuclease activities in restriction endonuclease preparations
      using an enforcement plasmid for kanamycin-resistance selection.
AB  - A new enforcement (kyosei-) cloning plasmid vector, designated pKF4, was
      constructed which confers kanamycin resistance (KmR) and enforces streptomycin
      sensitivity (SmS). Since it is important to employ restriction endonuclease
      (ENase) preparations free of exonuclease (Exo) activities for effective use of
      the kyosei-cloning procedure [Hashimoto-Gotoh et al., Gene 137 (1993) 211-216],
      ENases such as HpaI and SmaI purchased from four different suppliers were
      examined for possible contamination by exonucleases using pKF4. The plasmid DNA
      was digested with either ENase, ligated and transformed into Escherichia coli
      mutants, rpsL, supE, trpR. With pKF4 intact DNA (approx. 8 ng), 2.3 x 10(5) KmR
      transformant and four KmRSmR transformant colonies were obtained; the efficiency
      of transformation plating (ETP) of the intact DNA was approx. 2 x 10(-5). On the
      other hand, the ETP values were significantly higher by one to three orders of
      magnitude when cut and re-joined DNAs were used under the same conditions in six
      out of eight ENase samples examined. The results indicate that even commercially
      supplied ENases, that should have passed their quality control test, could have
      been contaminated with Exo sufficient to interfere with effective use of the
      kyosei-cloning method. Therefore, it is advisable to examine ENase samples for
      possible contamination with Exo activities, in order to choose the right
      preparations for this method at the beginning of the experiments.

PMID- 7590319
TI  - pALEX, a dual-tag prokaryotic expression vector for the purification of full
      length proteins.
AB  - pALEX, a prokaryotic expression vector, was constructed in which the multiple
      cloning site (MCS, polylinker) is flanked by sequences encoding glutathione S
      transferase (GST) at the 5' end and a His6 residue tag at the 3' end. Open
      reading frames cloned into this vector can direct production of fusion proteins
      with GST at their N terminus and a His6 tag at their C terminus. This allows for
      the purification of full-size fusion proteins by a sequential two-step procedure
      on glutathione-agarose and Ni(2+)-agarose columns.

PMID- 7590320
TI  - Single-step assembly of a gene and entire plasmid from large numbers of
      oligodeoxyribonucleotides.
AB  - Here, we describe assembly PCR as a method for the synthesis of long DNA
      sequences from large numbers of oligodeoxyribonucleotides (oligos). The method,
      which is derived from DNA shuffling [Stemmer, Nature 370 (1994a) 389-391], does
      not rely on DNA ligase but instead relies on DNA polymerase to build increasingly
      longer DNA fragments during the assembly process. A 1.1-kb fragment containing
      the TEM-1 beta-lactamase-encoding gene (bla) was assembled in a single reaction
      from a total of 56 oligos, each 40 nucleotides (nt) in length. The synthetic gene
      was PCR amplified and cloned in a vector containing the tetracycline-resistance
      gene (TcR) as the sole selectable marker. Without relying on ampicillin (Ap)
      selection, 76% of the TcR colonies were ApR, making this approach a general
      method for the rapid and cost-effective synthesis of any gene. We tested the
      range of assembly PCR by synthesizing, in a single reaction vessel containing 134
      oligos, a high-molecular-mass multimeric form of a 2.7-kb plasmid containing the
      bla gene, the alpha-fragment of the lacZ gene and the pUC origin of replication.
      Digestion with a unique restriction enzyme, followed by ligation and
      transformation in Escherichia coli, yielded the correct plasmid. Assembly PCR is
      well suited for several in vitro mutagenesis strategies.

PMID- 7590323
TI  - Purification of the KpnI DNA methyltransferase and photolabeling of the enzyme
      with S-adenosyl-L-methionine.
AB  - An Escherichia coli strain overproducing the KpnI DNA methyltransferase (M.KpnI)
      was constructed by cloning the kpnIM gene downstream from the inducible T7 phage
      luminal diameter 10 promoter. A method involving three chromatographic steps has
      been developed to purify M.KpnI to homogeneity. The purified enzyme has a pH
      optimum around 7.3 and is inhibited by salts. M.KpnI can be photolabeled by UV
      irradiation of the enzyme in the presence of S-adenosyl-L-[methyl-3H]methionine
      ([methyl-3H]AdoMet). Photolabeling results from a specific interaction between
      M.KpnI and AdoMet, as indicated by the dependence of photolabeling on native
      enzyme conformation and by the inhibitory effect of the AdoMet analogs,
      sinefungin and S-adenosyl-L-homocysteine (AdoHcy).

PMID- 7590322
TI  - Template secondary structure can increase the error frequency of the DNA
      polymerase from Thermus aquaticus.
AB  - Amplification of portions of the intergenic spacer between the katE gene and
      cryptic cel operon of Escherichia coli was accomplished by the polymerase chain
      reaction using the DNA polymerase from Thermus aquaticus. Nine different segments
      were amplified and cloned without error, but one 83-bp fragment was amplified
      with a high error rate such that 32 of 34 selected clones had three or more
      nucleotide changes from the expected sequence. The changes were all located in
      two 9-bp segments immediately adjacent to the 3'-ends of the two primers. Moving
      the end points of the primers to increase the spacing between them resulted in
      the isolation of significantly fewer error-containing products. It is proposed
      that stem-loop structures in the template immediately downstream from the primers
      interfere with an early stage of elongation and cause misincorporation. This is
      supported by the observation that destabilisation of one of the stem-loop
      structures reduced the frequency of errors.

PMID- 7590321
TI  - A versatile low-copy-number cloning vector derived from plasmid F.
AB  - We have constructed a cloning vector based on plasmid mini-F for use in
      Escherichia coli. Plasmid pZC320 consists of the ori-2 replication unit of F that
      confers very low copy number (lcn), and includes the sop partition functions to
      insure stable plasmid maintenance in the absence of selection. A multiple cloning
      site (MCS) containing 16 unique restriction sites is located within the 5' end of
      the lacZ alpha gene. Expression of lacZ alpha is under the control of the wild
      type lactose operator/promoter (lacOP) region and is efficiently repressed by the
      lacI repressor. Clones containing inserts can be detected using the blue/white
      screen for beta-galactosidase (beta Gal). A T7 promoter allows transcription of
      cloned inserts in the presence of T7 RNA polymerase. We have demonstrated the use
      of this lcn vector for cloning the regulated tetracycline-resistance genes from
      Tn10, which confer only low-level resistance when present at high copy number.

PMID- 7590324
TI  - A novel repetitive sequence lies near the gene encoding a cytosine
      methyltransferase in the cyanobacterium Dactylococcopsis salina.
AB  - An unusual cluster of tandemly repeated DNA sequences (TRS) was found downstream
      from the gene encoding DsaV methyltransferase, the DNA modification enzyme in the
      DsaV restriction-modification system found in a strain of Dactylococcopsis salina
      (Ds). The repeat unit is about 32-bp long and is present 13 times in the cluster.
      Each repeat unit can be divided into two distinct parts based on the level of
      sequence conservation and evolution. Hybridization of Ds DNA with a probe
      specific for this cluster revealed that there were at least two additional sites
      within the genome with similar TRS. The TRS units are localized in one region of
      the Ds genome. They do not share significant sequence similarity with other TRS
      found in prokaryotes.

PMID- 7590325
TI  - Phage RNA polymerase vectors that allow efficient gene expression in both
      prokaryotic and eukaryotic cells.
AB  - We have developed expression vectors that direct the synthesis of proteins from a
      common set of signals in both prokaryotic and eukaryotic cells. To allow
      transcription from a common promoter the vectors rely upon a phage RNA polymerase
      (RNAP). To direct initiation of translation to the same start codon the vectors
      utilize an internal ribosome entry site (IRES) from encephalomyocarditis virus
      (EMCV) that has been modified to include a prokaryotic ribosome-binding site
      (RBS) at an appropriate distance upstream from the desired start codon. These
      vectors provide levels of expression in eukaryotic cells that exceed those of a
      conventional RNAP-II-based system by 7-fold, and expression in bacterial cells at
      levels comparable to other phage RNAP-based systems. Inclusion of a lac repressor
      and a phage promoter/lac operator fusion element allows tight regulation.
      Cotransfection of eukaryotic cells with the expression vector and a vector that
      encodes the phage RNAP provides high-level transient expression without the need
      to construct specialized stable cell lines.

PMID- 7590326
TI  - An alternative sigma factor controls transcription of flagellar class-III operons
      in Escherichia coli: gene sequence, overproduction, purification and
      characterization.
AB  - Based on the studies of the FliA protein in Bacillus subtilis (Bs) and Salmonella
      typhimurium (St), the Escherichia coli (Ec) fliA gene has been proposed to encode
      a flagellar-specific sigma factor, sigma 28. In this study, the complete
      nucleotide (nt) sequence of Ec fliA was determined. The fliA coding region
      consists of 717 nt starting with a GTG start codon and ending with a TAA stop
      codon. The gene product is predicted to be 239 amino acids (26,435 Da). Sequence
      comparison between Ec FliA and the sigma 28 of St revealed 93.7% identity. Gene
      fliA was amplified by the polymerase chain reaction, subcloned into expression
      vector pT7-7, and overexpressed. The overproduced 28-kDa FliA protein, recognized
      by the St anti-sigma 28 antibody, was purified to homogeneity. The purified
      protein was able to initiate transcription from the tar promoter in the presence
      of RNP core enzyme. We conclude that FliA functions as an alternative sigma
      factor sigma 28 which is specific for flagellar operons in Ec.

PMID- 7590328
TI  - A Klebsiella aerogenes moaEF operon is controlled by the positive MoaR regulator
      of the monoamine regulon.
AB  - A 30-kDa protein accumulated upon induction by a high concentration of tyramine
      or dopamine in cells of Klebsiella aerogenes (Ka). These cells carried a plasmid
      (pAS123) that included the arylsulfatase operon (atsBA). Deletion analysis showed
      that the region essential for induction of the 30-kDa protein was located within
      a 2.0-kb cloned segment downstream of the atsBA operon. The nucleotide (nt)
      sequence of the 2.0-kb fragment revealed two open reading frames (ORFs), moaE and
      moaF. Transcription from a putative promoter of moaE was induced by the addition
      of tyramine, and the moaF gene was co-transcribed from this monoamine-inducible
      Ka promoter. The deduced Ka MoaE protein was homologous to insect-type alcohol
      dehydrogenase. The sequence of the 18 amino acids from the N-terminus of the
      purified 30-kDa protein agreed with that deduced from the nt sequence of moaF.
      Using a Ka strain with a mutant moaR gene, we found that MoaR, that acts as the
      positive regulator of the monoamine regulon, also acts as the positive regulator
      of the moaEF operon.

PMID- 7590329
TI  - Versatile, multi-featured plasmids for high-level expression of heterologous
      genes in Escherichia coli: overproduction of human and murine cytokines.
AB  - We describe the construction, expression characteristics and some applications of
      a versatile dual-promoter expression plasmid for heterologous gene expression in
      Escherichia coli which contains both lambda pL and PT7 promoters. Furthermore,
      the plasmid is optimized to allow the expression of mature coding sequences
      without compromising the strength of the highly efficient PT7 or of the T7g10
      ribosome-binding site. The effect of the the naturally occurring RNA loops at
      both the 5' and 3' ends of the T7g10 mRNA on expression was also examined. A
      double T7 RNA polymerase transcription terminator was inserted to ensure more
      reliable transcription termination and a higher expression level of the preceding
      gene. Further improvements involve a clockwise orientation of the promoters to
      minimize read-through transcription from plasmid promoters, a largely extended
      multiple cloning site, an antisense phage T3 promoter and a phage f1-derived,
      single-stranded replication origin. Variants of this plasmid allow for the
      production of fusion proteins with part of T7g10, a hexahistidine peptide and an
      enterokinase recognition site. The potential of these expression vectors is
      demonstrated by comparing the expression levels of a number of mammalian
      cytokines (human tumor necrosis factor, human immune interferon, human and murine
      interleukins 2, murine interleukin 4 and murine fibroblast interferon), using
      these expression plasmids.

PMID- 7590327
TI  - Revision of the amino-acid sequence of 3-isopropylmalate dehydrogenase from
      Salmonella typhimurium by means of X-ray crystallography.
AB  - The amino acid (aa) sequence of the leuB gene product of Salmonella typhimurium,
      3-isopropylmalate dehydrogenase (IPMDH), has been revised using electron density
      maps from X-ray structure determination. The nucleotide (nt) sequence of both
      strands of leuB has been redetermined to confirm the crystallographic findings.
      It does not agree with the previously reported S. typhimurium leuB nucleotide
      sequence [Andreadis and Rosenthal, Biochim. Biophys. Acta 1129 (1992) 228-230].

PMID- 7590331
TI  - A system utilizing Epstein-Barr virus-based expression vectors for the functional
      cloning of human fibroblast growth regulators.
AB  - The acquired ability of adherent mammalian cells to grow in suspension is closely
      linked to tumorigenic transformation. The anchorage-independence phenotype is
      likely to result from bypassing an adherence-responsive cell-cycle check-point at
      the G1/S boundary of the cell cycle. In order to identify genes that are part of
      or act upon the anchorage signal transduction pathway, we have developed a system
      which allows functional cloning of regulatory genes by expression of libraries of
      cDNA inserts either in the sense or antisense direction. The system is comprised
      of two components: (i) the library expression vectors, CMV-EL and C1E-EL,
      containing EBoriP for replication in EBN A-1-expressing cells, an expression
      cassette with a multiple cloning site suitable for directional insertion of cDNA
      libraries generated by standard protocols, and loxP sites which allow rapid
      manipulation of recovered vectors without the use of restriction enzymes and (ii)
      the EBNA-1-producing cell line, BB-5, a derivative of the immortalized, non
      tumorigenic and anchorage-dependent human fibroblast cell line, MSU1.1. The
      growth characteristics of BB-5 cells did not differ from its parental cell line.
      BB-5 cells supported the episomal replication of CMV-EL and C1E-EL and allowed
      recovery of the vector from Hirt lysates of transfected BB-5 cells. BB-5 cells
      transformed to anchorage-independent growth by transfection with a mutant c-Ha
      ras gene inserted into CMV-EL could be accurately and efficiently identified in a
      background of non-transfected BB5 cells by screening for anchorage-independent
      colonies with the aid of computer-assisted image analysis.

PMID- 7590330
TI  - Sequence of a novel virulence-mediating gene, virC, from Vibrio anguillarum.
AB  - Previously, the double-transposon (Tn) mutant VAN20 of Vibrio anguillarum (Va)
      775.17B was isolated. This mutant lacked a major surface antigen (MSA) suggested
      to be a lipopolysaccharide (LPS) and showed a 10(5)-fold increase in the 50%
      lethal dose (LD50) when fish were infected intraperitoneally. In this study, the
      two Tn insertion sites within the chromosome were identified, a plasmid insertion
      mutation was made at each locus in a more virulent strain of Va, NB10, and the
      virulence was analyzed. One mutant displayed a 10(4)-fold increase in LD50,
      whereas the second mutant showed the wild-type (wt) phenotype. However, both
      mutants still expressed the MSA, suggesting that there may be more than two Tn
      insertions in VAN20 or that a double mutation is required to prevent production
      of the MSA. The DNA locus for the virulent phenotype was cloned and sequenced. A
      potential transcriptional unit consisting of three putative open reading frames
      (ORFs) was identified. The Tn was located in the second ORF, virC (virulence).
      The first ORF (34.8 kDa) showed 30% homology to the Escherichia coli and
      Salmonella typhimurium cysG (cysteine) genes. The virC gene (51.4 kDa) and the
      third ORF (24 kDa) showed no homology to other proteins in GenBank. Plasmid
      insertion mutants were made within each of these ORFs and the virulence was
      assayed. Only the virC mutant showed a loss in virulence, indicating that virC is
      a novel gene that is essential for the virulence of Va.

PMID- 7590333
TI  - Purification of a high-mobility-group 1 sea-urchin protein and cloning of cDNAs.
AB  - The isolation of the sea urchin high-mobility-group 1 (HMG1) protein, the cloning
      of corresponding cDNA clones and the similarity to the human homologue are
      described. Sea urchin HMG1 was purified as one of the nuclear embryonic proteins
      which associate with an upstream regulatory element (E1) of the
      Strongylocentrotus purpuratus (Sp) CyIIIb actin-encoding gene. Using a synthetic
      oligodeoxyribonucleotide (oligo) which includes the E1 cis-acting element in a
      DNA affinity chromatography purification, the most prominent of the binding
      proteins was isolated and the N terminus sequenced. cDNA clones were isolated by
      screening an embryonic cDNA library with a synthetic oligo derived from the amino
      acid (aa) sequence. Comparison of the cDNAs ORF to known proteins revealed a 50%
      aa identity to the mammalian HMG1 and all the structural characteristics of this
      group of proteins. The sea urchin protein, SpHMG1, was synthesized in bacteria,
      as well as translated in vitro. Binding assays carried out with the recombinant
      SpHMG1 protein did not produce specific in vitro complexes with E1.

PMID- 7590332
TI  - A human antibody specific for hepatitis C virus core protein: synthesis in a
      bacterial system and characterization.
AB  - The cDNA coding for the Fab fragment of the human B12.F8 antibody (Ab), directed
      against the putative nucleocapsid component (core protein) of hepatitis C virus
      (HCV), was cloned in the prokaryotic phagemid vector, pHEN-1, to obtain its
      expression in Escherichia coli. The functionality and specificity of the
      recombinant Ab, called B12Fab, were examined by Western blot and ELISA using
      recombinant HCV core protein as antigen. The specificity of B12Fab was further
      confirmed by ELISA with the 33-mer peptide epitope recognized by the original
      whole B12.F8 Ab. By immunofluorescence, the recombinant B12Fab was shown to
      recognize HCV core protein produced in cells transfected with HCV cDNA,
      indicating that the recombinant B12Fab is suitable as a diagnostic tool for
      tissue localization of the virus. The B12Fab also functioned when displayed on
      phage particles, providing the basis for future experiments of in vitro affinity
      maturation and selection of mutants. The variable chain coding regions of the
      recombinant B12Fab clone were sequenced and the V-gene usage was determined by
      comparison with the V kappa and VH germline sequences. The B12Fab V kappa chain
      belongs to the subgroup II and shows the highest degree of homology with the A3
      germline gene, whereas the sequence of the VH chain is strictly related to that
      of the Humhv3019b18 gene of the VH3 family. These results are, to our knowledge,
      the first report of molecular cloning and characterization of a functional human
      Ab specific for an HCV antigen.

PMID- 7590334
TI  - High-density cDNA filter analysis of the expression profiles of the genes
      preferentially expressed in human brain.
AB  - We previously established a method, called high-density cDNA filter analysis
      (HDCFA), for analyzing the expression profiles of a large number of genes in a
      systematic manner. In the present study, we constructed a cDNA filter of about
      8300 cDNAs from a human cerebral cortex cDNA library and quantitatively analyzed
      their expression in human adult brain, fetal brain, kidney and liver using HDCFA.
      Using a comparison of the relative amount of expression of each clone in
      different tissues and following (partial) sequence analysis, about 200 clones
      were selected as those preferentially expressed in adult or fetal brain, one half
      of which may be unknown. Their expression was further analyzed in human
      neuroblastoma cell lines, a human glioma cell line, human cerebral cortex,
      cerebellum and kidney. Finally, eight clones were selected and sequenced as
      characteristically expressed genes (cDNAs). A homology search revealed that three
      clones were human homologues of the rat genes preferentially expressed in brain
      and five clones were unknown. The full-length cDNA sequence of one of the unknown
      clones was determined.

PMID- 7590335
TI  - Positive regulation of human alpha 1 (I) collagen promoter activity by
      transcription factor Sp1.
AB  - Analysis of the regulatory promoter region of the human alpha 1 (I) collagen
      encoding gene (COL1A1) gene indicated the presence of G+C-rich sequence elements
      that are potential binding sites for the transcription factor Sp1. As a step
      toward understanding transcriptional regulation of the human COL1A1, we examined
      Sp1 binding in the promoter region using DNase I footprinting, and analyzed the
      effect of Sp1 expression on COL1A1 promoter activity in transiently transfected
      Drosophila melanogaster cells in vivo. The results indicated that recombinant
      human Sp1 interacted specifically with two G+C-rich sequences within the COL1A1
      promoter. Binding of factors in nuclear extracts prepared from human dermal
      fibroblasts to a 22-nucleotide deoxyribonucleotide (oligo) spanning the 5' G+C
      rich sequence required Zn2+, and was abolished by excess Sp1 consensus binding
      site oligos, or by anti-Sp1 antibodies. Studies in which a series of
      progressively 5'-deleted COL1A1 promoter::cat constructs were co-expressed with
      an Sp1 expression plasmid in a cellular background devoid of Sp1 homology
      demonstrated that Sp1 markedly enhanced the COL1A1 promoter activity. These
      results suggest that the transcriptional activity of the human COL1A1 can be
      positively regulated by Sp1.

PMID- 7590336
TI  - Characterization of the promoter of the human KAL gene, responsible for the X
      chromosome-linked Kallmann syndrome.
AB  - We report on the first characterization of the human KAL promoter (pKAL), based
      on the analysis of a 2-kb fragment of the 5' flanking region. As determined by
      primer extension, transcription of the human KAL gene is initiated at two
      different sites in the quail embryonic neuroretina QNR/D cell line. The promoter
      region is G+C rich and contains a CCAAT box, two binding sites for the SP1
      transcription factor and two AP2-binding sites, but no TATA box. It also shares a
      motif with several neural-specific genes. The ability of four deletion mutants to
      drive transcription of the heterologous chloramphenicol acetyltransferase (CAT)
      encoding gene was determined in transfection experiments. The mutant containing
      the KAL sequence from nt +2 to -435 demonstrated a tissue-specific, although
      weak, transcriptional activity only in the quail embryonic neuroretina K2 and
      QNR/D cell lines. Longer constructs did not confer any activity. Therefore, we
      suggest that this 437-bp segment of pKAL constitutes a neural-specific promoter
      which could be negatively controlled by upstream sequences.

PMID- 7590338
TI  - The mitochondrial pyruvate dehydrogenase complex: nucleotide and deduced amino
      acid sequences of a cDNA encoding the Arabidopsis thaliana E1 alpha-subunit.
AB  - A cDNA encoding the E1 alpha subunit of the Arabidopsis thaliana (At)
      mitochondrial (mt) pyruvate dehydrogenase complex (PDC) was sequenced. The 1435
      bp cDNA consists of a 1167-bp open reading frame encoding a 43.0-kDa polypeptide
      of 389 amino acids (aa) (pI 7.1). The plant E1 alpha subunit has 47-51% aa
      sequence identity with other eukaryotic sequences. Among the regions that are
      highly conserved are the aa surrounding phosphorylation sites 1 and 2 of the
      mammalian sequence, including the conserved Ser292 residue of At at site 1. An
      essential active site residue, Cys62 of the bovine subunit, is also conserved. A
      32-aa presumptive mt targeting sequence is present at the N terminus.

PMID- 7590337
TI  - A human pancreatic secretory trypsin inhibitor presenting a hypervariable highly
      constrained epitope via monovalent phagemid display.
AB  - Hypervariable gene banks displaying ligands which can be used for affinity
      optimisation are valuable resources for examining shape space. They have added
      value if the ligand is small, if there is extensive information on its tertiary
      structure and if the variable region is highly constrained. These features would
      be expected to stabilise complexes by reducing the dissociation constants and to
      facilitate their use as 'lead substances' for the development of synthetic
      mimetics. The synthesis and characterisation of such phagemid-display banks is
      described here, in which the variable region is a 7-amino acid (aa) (pSKAN8
      HyB/C) or 8-aa (pSKAN8-HyA) extended peptide held between two disulfide bridges
      at the exposed tip of the human pancreatic secretory trypsin inhibitor (PSTI). A
      phagemid pSKAN8 was created which contains a fusion between the PSTI and M13 pIII
      protein-coding genes. Cassettes containing the sequences (NNK)8 [HyA], (NNK)7
      [HyB] or (NNK)6GTT [Hy-C] (where K = G or T) were used to randomize the aa coding
      region in the trypsin-inhibitory loop (aa 17 to 23) of PSTI. Some 31 million
      individual clones were generated in a mutS Escherichia coli strain kept as frozen
      cell stocks. Analysis of controls which had not undergone selection showed very
      low levels of deletion. The quality of the hypervariable region and bias of codon
      usage was quantified by DNA sequencing. It was estimated from SDS-PAGE that
      hybrid protein was represented statistically at a frequency of one molecule per
      two phagemid particles. The functionality and reproducibility of the system was
      demonstrated by trypsin-binding of the original vector and in selecting novel
      chymotrypsin inhibitors from the banks.

PMID- 7590339
TI  - Cloning, expression and immunological characterization of Ory s 1, the major
      allergen of rice pollen.
AB  - We have isolated and characterized a cDNA clone, Ory s 1, encoding a group-1
      allergen of rice pollen. The Ory s 1 protein shows significant sequence identity
      to the major allergen of rye-grass pollen, Lol p 1. RNA gel blot analysis shows
      that the Ory s 1 gene is expressed in mature anthers, but not in vegetative or
      other floral tissues tested. Southern blot analysis indicates that this clone
      represents a member of a small gene family in rice. Western blot analyses of
      total rice pollen proteins with the group-1 allergen-specific monoclonal 3A2 and
      IgE antibodies from grass pollen-allergic patients, revealed the presence of
      cross-reactive antigenic and allergenic epitopes in Ory s 1.

PMID- 7590340
TI  - Nucleoside diphosphate kinase from the parasitic nematode Brugia malayi.
AB  - Using a reverse transcription-polymerase chain reaction (RT-PCR) procedure that
      exploited the presence of a conserved 22-nucleotide spliced leader (SL) sequence
      that is trans-spliced to the 5' end of nematode transcripts, a novel Brugia
      malayi (Bm) infective-stage SL cDNA expression library was constructed and
      characterized. The library was immunoscreened with rabbit anti-infective-stage
      antibodies (Ab) and an immunodominant clone, BmG4-7, was identified and
      characterized. BmG4-7 contained a full-length cDNA that had significant sequence
      similarity to nucleoside diphosphate kinase (NDK)-encoding sequences reported
      from a number of species, including Drosophila melanogaster and humans. BmNDK was
      found to be constitutively transcribed during all stages of parasite development.
      An anti-BmNDK Ab was used to immunostain a Western blot of extracts from adult
      and larval parasites. The Ab specifically recognized a 17.5-kDa molecule in all
      of the parasite extracts. Molecular modeling of the BmNDK showed several regions
      surrounding the conserved catalytic site that may be important in the design of
      drugs specific for the disruption of NTP synthesis in filarial parasites.

PMID- 7590344
TI  - Clusters of modular regulatory elements at DNA replication origins.
AB  - To study the specificity of eukaryotic origins of replication (ori), we have
      isolated a fraction of mouse DNA enriched in replication initiation sequences
      (RIS), and cloned and characterised some of these RIS. The sequences of three RIS
      were analysed for the presence of sequence elements common to other known
      eukaryotic ori. It was found that the three RIS were A+T rich and contained a
      number of sequence elements that may function in the initiation of DNA
      replication. The data support the idea that mammalian ori are organised from
      modular sequence elements.

PMID- 7590345
TI  - Rapid identification and isolation of transcriptionally active regions from mouse
      genomes.
AB  - We report here the design, construction and testing of a self-inactivating (Sin)
      retrovirus promoter-trap vector suitable for identifying and isolating
      transcriptionally active regions from the mouse genome. When this vector, which
      contains the bacterial aph gene as its reporter, is integrated into a site
      downstream from an active host cell promoter, it expresses aph, whose product,
      aminoglycoside phosphotransferase, produces resistance to the antibiotic G418 in
      mammalian cells. The construct also contains a native aph promoter which
      functions in bacteria, but not in mouse cells, to express kanamycin (Km)
      resistance, plus an adjacent pBR322-derived replication origin. Thus, mammalian
      DNA segments containing actively transcribed regions flanking aph can be quickly
      isolated by restriction endonuclease treatment of total DNA from provirus
      containing mouse cells, followed by self-ligation, transformation and Km
      selection of plasmids carried by bacteria transformed with this DNA. We tested
      this Sin retrovirus promoter-trap system by isolating eight DNA segments upstream
      to the provirus integration sites in the genome of virus-infected mouse F9 cells.
      We found that the Sin retrovirus vector produces a high yield of infectious virus
      particles carrying aph, and that the isolated genomic DNA fragments of F9 cells
      are transcriptionally active.

PMID- 7590347
TI  - Structure of the gene encoding the mouse pituitary adenylate cyclase-activating
      polypeptide receptor.
AB  - The PACAP-R gene, encoding the mouse pituitary adenylate cyclase-activating
      polypeptide receptor (PACAP-R), has been isolated and its structural organization
      has been determined. PACAP-R spans more than 50 kb and is divided into 18 exons.
      PACAP-R contains two alternative exons encoding the putative third intracellular
      loop, as found in the rat PACAP-R. The proximal promoter region is highly G+C
      rich and lacks an apparent TATA box, but contains a CCAAT box and two potential
      Sp1-binding sites.

PMID- 7590346
TI  - Cloning and chromosomal mapping of the mouse Mgat3 gene encoding N
      acetylglucosaminyltransferase III.
AB  - Complex and hybrid N-linked carbohydrates synthesized by mammalian cells may
      possess a N-acetylglucosamine residue known as the bisecting GlcNAc. The transfer
      of this residue is catalyzed by the enzyme UDP-N-acetylglucosamine:beta-D
      mannoside beta 1,4-N-acetylglucosaminyltransferase III (GlcNAc-TIII; EC
      2.4.1.144). To begin to investigate biological functions for carbohydrates with a
      bisected GlcNAc residue, we have cloned and partially characterized the mouse
      gene (Mgat3) encoding GlcNAc-TIII. A rat GlcNAc-TIII-encoding cDNA was used to
      isolate clones from a mouse strain 129 Sv liver genomic DNA library. An NsiI
      genomic DNA fragment containing an ORF with 96% identity to rat GlcNAc-TIII was
      subcloned into a mammalian expression vector and transfected into Chinese hamster
      ovary (CHO) cells. The transfectants expressed GlcNAc-TIII activity only when the
      ORF was in the sense orientation. Southern analysis showed that Mgat3 is present
      in a single copy in the mouse genome. Mapping by restriction-fragment length
      polymorphism analysis of backcross progeny located Mgat3 to mouse chromosome 15,
      at a position homologous with region 22q12.3-q13.1 in the human genome. Northern
      analyses of adult tissues showed that Mgat3 is expressed at high levels in kidney
      and brain, and at lower levels in many other tissues.

PMID- 7590343
TI  - Sequence of a cDNA encoding turtle riboflavin-binding protein: a comparison with
      avian riboflavin-binding protein.
AB  - To search for the existence and distribution of a riboflavin-binding protein
      (RfBP), total RNA from estrogen-treated oviparous animals were screened by
      Northern hybridization using chicken RfBP cDNA as a probe. Besides avian livers
      and oviducts, RfBP mRNA was found in turtle liver, but not in the turtle oviduct.
      To elucidate the structure of the RfBP from a reptilian source, we constructed a
      cDNA library from estrogen-injected turtle liver, and a full-length turtle RfBP
      encoding cDNA was cloned and sequenced. The open reading frame (ORF) encoded 242
      amino acids (aa) including a signal peptide of 18 aa. There is an overall 71.3%
      aa identity between the deduced aa sequences of turtle and chicken. The aa
      sequence of turtle and chicken RfBP also show more than 30% similarity to a
      fragment of folate-binding protein (FBP). Six Trp and nine pairs of Cys residues
      are conserved between the two RfBPs with only one pair of Cys residues missing in
      FBP. The two Asn-linked glycosylation sites found in chicken RfBP are conserved
      in turtle RfBP, but only one of which is conserved in FBP. However, there is an
      additional potential N-glycosylation site in the turtle sequence and this may
      provide a better explanation for the greater molecular weight of the turtle
      protein than chicken RfBP. Turtle RfBP contains a region of nine Ser and five Glu
      residues which is present in mature chicken RfBP as eight phosphorylserine
      clusters forming a highly anionic region at the C terminus, but this region is
      not found in FBP.

PMID- 7590341
TI  - A cDNA clone from the sea lamprey Petromyzon marinus coding for a scavenger
      receptor Cys-rich (SRCR) domain protein.
AB  - Our knowledge of the immune system in the early vertebrates, the Agnatha, and the
      molecules involved in their immune reactions is fragmentary. By serendipity we
      discovered a cDNA clone in a library made from gut poly(A)+RNA of the sea
      lamprey, Petromyzon marinus (Pema), that translates into the SREG (SRCR-EGF, see
      below) protein which resembles cell-membrane proteins of mammalian immune cells.
      The putative translated product is a type-I integral membrane glycoprotein which
      contains two scavenger receptor Cys-rich (SRCR) domains flanking five epidermal
      growth factor (EGF)-like repeats. The two SRCR domains are closely related to CD6
      (expressed on human lymphocytes), WC1 (expressed on mammalian CD4-CD8(-)-gamma
      delta T cells) and M130 (expressed on human macrophages). The Pema-SREG may
      therefore be involved in intercellular contacts and cell activation or
      differentiation in the immune system. It is thus a potential marker that can be
      used to investigate the lamprey immune system.

PMID- 7590348
TI  - Cloning and sequence analysis of the murine glucagon receptor-encoding gene.
AB  - The glucagon receptor (GR) plays a central role in regulating the level of blood
      glucose by controlling the rate of hepatic glucose production and insulin
      secretion. To study the integrated role of a candidate gene such as GR in whole
      body glucose homeostasis by molecular genetic manipulation, cloning of the gene
      is required. We have cloned and sequenced the murine GR cDNA, gene and promoter
      region, and studied its tissue distribution. Murine GR contains 13 exons which
      are located in a region of 4.0 kb. GR encodes a 485-amino-acid protein that
      consists of seven putative transmembrane domains. By RT-PCR analysis, we have
      determined that GR is expressed predominantly in liver, kidney, adrenal, lung and
      stomach, while lower levels of expression are detected in brown and white adipose
      tissue, cerebellum, duodenum and heart. In addition, a 1000-bp region of the GR
      promoter has been sequenced which contains consensus sequences for putative DNA
      binding proteins involved in tissue specificity (c/EBP; HNFI) or hormonal
      regulation (steroid receptor). Other consensus sequences known to function in
      controlling basal promoter activity, such as AP1, AP2 and Sp1, are also present.
      Conversely, no evident TATA or CAAT boxes are present. We provide here important
      new information necessary for the future pursuit of genetic manipulations in the
      mouse.

PMID- 7590350
TI  - The cDNA cloning and expression of the gene encoding rat gelatinase B.
AB  - During a study aimed at defining the role of tissue remodeling genes implicated
      in wound healing, we isolated cDNA clones encoding gelatinase B (GelB) from a
      cDNA library derived from healing rat skin wound. The predicted rat GelB
      comprising 708 amino acids shows 75% and 82% identity with the human and mouse
      GelB, respectively. By Northern blot analysis, two GelB transcripts of 2.4 and
      3.0 kb were observed in rat tissues, and shown to arise through the differential
      use of polyadenylation signals. Recombinant rat pro-GelB produced in transfected
      COS-1 cells exhibited a molecular weight of 92 kDa, as shown by gelatin
      zymography. Autocatalytic processing to active lower-molecular-weight forms was
      induced by 4-aminophenylmercuric acetate, and this process was inhibited in the
      presence of EDTA.

PMID- 7590349
TI  - A mRNA variant encoding a soluble form of 4-1BB, a member of the murine NGF/TNF
      receptor family.
AB  - The murine 4-1BB gene, encoding a member of the nerve growth factor/tumor
      necrosis factor (NGF/TNF) receptor family, is thought to be selectively expressed
      in T cells and is involved in the regulation of lymphocyte proliferation. We
      detected two forms of the 4-1BB mRNA by RT-PCR which were expressed in an
      activation-dependent pattern in splenocytes and thymocytes. cDNA sequencing
      showed that the smaller form was a mRNA splice variant lacking the transmembrane
      region (4-1BB delta TM), because of the deletion of exon 8. The two forms of mRNA
      are differentially expressed in murine T cells, macrophages, 3T3 fibroblasts and
      epitheloid cells. Northern blotting also identifies two forms of mRNA of 1.5 and
      2.4 kb, and the cell-type-specific pattern correlated with the PCR results. These
      results identify a novel form of 4-1BB. This and the previously known membrane
      associated form have a broad tissue distribution, suggesting a more diverse role
      in host defense.

PMID- 7590342
TI  - The rhodopsin-encoding gene of bony fish lacks introns.
AB  - A study of the sequences of the rhodopsin-encoding genes (Rh) in eight fish
      species from two of the major subdivisions of the teleosts reveals that no
      introns are present in the coding region. This contrasts with the opsin-encoding
      genes of all other vertebrates where either four or five introns are invariably
      found. Phylogenetic analysis shows that this intronless teleost Rh is homologous
      to the intron-containing Rh of amphibia, birds and mammals. Possible mechanisms
      for intron loss are discussed, including replacement by homologous conversion of
      Rh with a processed cDNA.

PMID- 7590352
TI  - Cloning and characterization of the bovine polymeric immunoglobulin receptor
      encoding cDNA.
AB  - Trans-epithelial transport of polymeric immunoglobulins (pIg) into mucosal and
      glandular secretions is carried out by the pIg receptor (pIgR). Therefore,
      expression of the pIgR gene in epithelial cells of mucosal and glandular tissues
      is an absolute requirement for achieving mucosal immunity. We report the cloning
      and characterization of the bovine pIgR cDNA. Three overlapping cDNA clones with
      a total length of 3608 bp yielded an open reading frame encoding a 757-amino-acid
      (aa) transmembrane (TM) glycoprotein. Although polymorphism was found in two
      separate clones, Northern blot analysis showed a single pIgR mRNA (approx. 3.8
      kb) to be present in the mammary gland, liver, lung, kidney and intestine of a
      lactating cow. There was no detectable expression of pIgR in the spleen of the
      same animal. Comparison of the deduced bovine pIgR as sequence with those of rat,
      mouse, man and rabbit shows that this receptor is highly conserved both in aa
      sequence and structural organization. The degree of conservation in the TM
      sequence and the C-terminal cytoplasmic tail, which contains the various signals
      for intracellular trafficking of the receptor, is 65-73%. We also find a high
      degree of conservation (61-66%) in the ectoplasmic part of the receptor, known as
      the secretory component (SC), with an exception for that of the rabbit SC, which
      is much lower (47%). Among the five Ig-like domains in the SC, the N-terminal
      domain I, where the primary pIg-binding site is located, showed the highest (72
      83%) aa sequence conservation.

PMID- 7590351
TI  - The bovine DNA polymerase beta promoter: cloning, characterization and comparison
      with the human core promoter.
AB  - The core promoter of the human DNA polymerase beta (beta Pol)-encoding gene (POL
      beta) is regulated through cis-elements for the ATF/CREB protein(s), and GC box
      binding and initiation-site-binding proteins. The mechanism of promoter
      regulation has been studied using a nuclear extract transcription system from
      HeLa cells [Narayan et al., J. Biol. Chem. 269 (1994) 12755-12763]. To study the
      homologous promoter (ppol beta) in a bovine system, we cloned and characterized
      the 5'-flanking region of the bovine gene (pol beta). A 15.3-kb fragment of
      bovine genomic DNA containing the first two exons and 11 kb of 5'-flanking region
      was isolated from a testis library in bacteriophage lambda EMBL3. S1 nuclease
      mapping and primer extension analysis of the 5'-end of the pol beta mRNA
      identified the major transcription start point (tsp), which is located 142-bp 5'
      of the translational start codon. In transient expression assays using a bovine
      cell line, analysis of various 5'-deletion mutants demonstrated that a fragment
      of only 91-bp 5' of the tsp had promoter activity similar to that of a 1.37-kb
      fragment, so that cis-elements for basal transcription are located within this
      approx. 100-bp core promoter, as in the human promoter (pPOL beta). Comparison of
      the core promoters from the bovine and human genes revealed striking similarity,
      including an almost precise match of the tsp, the ATF/CREB-binding and Sp1
      binding sites, and the spacing separating them.

PMID- 7590353
TI  - Restriction map of a 35-kb HLA fragment constructed by nested deletion 'drop-out'
      mapping.
AB  - An efficient method for generating detailed restriction maps of large cloned DNA
      segments is demonstrated. The mapping strategy entails comparing restriction
      fragments from a parent clone and from nested deletion derivatives of that clone.
      In a set of deletion plasmids of decreasing size, an individual fragment will be
      lost, or 'drop-out', according to its position in the cloned fragment. In this
      demonstration, nested deletions were generated in both directions in a 35-kb DNA
      segment from the human leukocyte antigen (HLA) region by intramolecular
      transposition of an engineered gamma delta (Tn1000) element present in a special
      'deletion factory' cloning vector [Wang et al., Proc. Natl. Acad. Sci. USA 90
      (1993) 7874-7878]. Fifteen plasmids with deletions extending in one direction and
      eleven plasmids with deletions extending in the opposite direction were digested
      singly by each of four restriction enzymes. A total of 36 cleavage sites were
      mapped in the 35-kb HLA fragment. This drop-out approach using nested deletions
      provides a simple and efficient means of mapping restriction sites, genes and
      other features of interest in cosmid-sized cloned DNA segments or DNAs.

PMID- 7590354
TI  - A high-level prokaryotic expression system: synthesis of human interleukin 1
      alpha and its receptor antagonist.
AB  - Synthetic intronless genes, coding for human interleukin 1 alpha (IL 1 alpha) and
      interleukin 1 receptor antagonist (IL1ra), have been expressed efficiently in a
      specially designed prokaryotic vector, pGMCE (a pGEM1 derivative), where the
      target gene forms the second part of a two-cistron system. The first part of the
      system is a translation enhancer-containing mini-cistron, whose termination codon
      overlaps the start codon of the target gene. In the case of the IL1 alpha gene,
      the high expression level is largely due to the direct efficient translation
      initiation at the second cistron, whereas with the IL1ra gene in the same system,
      the proximal translation initiation region (TIR) provides a high level of coupled
      expression of the target gene. Thus, pGMCE is a potentially versatile vector for
      direct prokaryotic expression.

PMID- 7590355
TI  - Cloning and characterization of cDNA encoding a human arginyl-tRNA synthetase.
AB  - Arginyl-tRNA synthetase (ArgRS) plays a key role in protein synthesis as part of
      a multienzyme complex with a number of other aminoacyl-tRNA synthetase (aaRS)
      enzymes. We have isolated a full-length cDNA encoding ArgRS as part of a project
      on complementation of radiosensitivity in human cells with an Epstein-Barr Virus
      (EBV) vector-based human cDNA library. DNA sequence analysis identified an open
      reading frame of 1983 nucleotides with 87% homology to other mammalian ArgRS
      genes. The deduced amino acid (aa) sequence (661 aa) showed 87.7% identity to the
      Chinese hamster ovary (CHO) enzyme and 37.7% identity to the homologous
      Escherichia coli enzyme. Northern blot analysis revealed the presence of a single
      mRNA species of approx. 2.2 kb. The results described here demonstrate that ArgRS
      is highly conserved in mammalian cells and confirm the presence of a hydrophobic
      N-terminal region in the higher-molecular-weight complexed form of ArgRS.

PMID- 7590357
TI  - Isolation, characterization and chromosomal localization of a human pseudogene
      for hexokinase II.
AB  - A processed pseudogene for hexokinase II (HKII), the first such reported for a
      member of the hexokinase gene family, was isolated from a human genomic library
      by using a rat HKII cDNA as a probe. The pseudogene contains a region that is
      identical to the open reading frame of the human HKII cDNA at 97% of the
      nucleotide positions, but it contains several frameshift mutations, small
      deletions and insertions, and several stop codons. The human HKII pseudogene is
      located on the X chromosome and is integrated into a long interspersed nuclear
      repetitive DNA element (LINE). We estimate that this integration event occurred
      approximately 14-16 Myr (million years) ago.

PMID- 7590356
TI  - Mode of activation of the GC box/Sp1-dependent promoter of the human NADH
      cytochrome b5 reductase-encoding gene.
AB  - Many eukaryote promoters, particularly those for so-called housekeeping genes,
      have multiple GC boxes which are the binding sites of the transcription factor,
      Sp1. It has been proposed that Sp1 binds to the multiple GC boxes, and then the
      GC box-bound Sp1 interact with each other to synergistically stimulate
      transcription. Here, we describe a Sp1-dependent promoter which does not
      necessarily fit the synergistic activation mechanism. The promoter of the human
      NADH-cytochrome b5 reductase-encoding gene (CYTB5R) possesses five potential GC
      box sequences. Deletion and mutagenesis studies coupled with CAT assays revealed
      that three out of five GC box-like sequences were functionally active and
      activated transcription additively (rather than synergistically). Our results
      suggested that Sp1-mediated activation of transcription occurs in a promoter
      context-dependent manner.

PMID- 7590359
TI  - A sea urchin homologue of ceh-19, an unusual homeobox-containing gene from a
      nematode.
AB  - When screening for homeobox-containing genes from the sea urchin Heliocidaris
      erythrogramma (He), we isolated an exon of a gene which appears to be a homologue
      of the homeobox-containing gene, ceh-19, of Caenorhabditis elegans (Ce). The
      predicted translation of the sea urchin sequence shows 77% identity and 92%
      similarity to the first 53 amino acids of the homeodomain of ceh-19. The ceh-19
      gene exhibits an intron in an unusual location in the 3' end of the homeobox; the
      He gene shares this feature.

PMID- 7590358
TI  - Comparison of the structure and expression of the human and rat neprilysin
      (endopeptidase 24.11)-encoding genes.
AB  - The existence of a third non-coding exon in the human neprilysin-encoding gene (h
      NEP), positionally located as exon 3, has been demonstrated by reverse
      transcription of RNA from human kidney and lung, coupled with the polymerase
      chain reaction. Comparison of nucleotide sequences between h-NEP and the rat NEP
      (r-NEP) genes shows a high degree of sequence conservation within noncoding exons
      1 and 2. In contrast, the region of the gene containing exon 3 is highly
      divergent. Two transcripts derived from exon 2 by alternative splicing, type-2a
      and type-2b, were demonstrated in human kidney and lung. In contrast, only the
      type-2b transcript was present in these same tissues in the rat. The type-1
      transcript was detected in human kidney, lung and brain, this transcript
      appearing to be the major species in brain.

PMID- 7590361
TI  - Sequence of a chicken erythroblast mono(ADP-ribosyl)transferase-encoding gene and
      its upstream region.
AB  - We have cloned the MADPRT gene encoding the 300-amino-acid mono(ADP
      ribosyl)transferase (MADPRT) from chicken erythroblasts. The protein has homology
      to the rabbit and human skeletal muscle (50% identity) and two chicken heterophil
      (52% identity) NAD+:arginine MADPRT. The active site region is particularly
      conserved. The upstream region of the MADPRT gene from erythroblasts has several
      features characteristic of promoter sequences.

PMID- 7590360
TI  - The sequence of a Xenopus laevis TFIID subunit reveals remarkable conservation
      among vertebrates.
AB  - A cDNA clone encoding a Xenopus laevis (Xl) homologue of human transcription
      factor IID (TFIID) subunit p80 was isolated and sequenced. The deduced 618-amino
      acid (aa) sequence was compared to the homologous from human, mouse, rat and
      Drosophila melanogaster (Dm). A highly conserved region exists in the central
      region among these species. In contrast, the C-terminal region has significant
      homology among vertebrates, whereas the corresponding region of the Dm homologue
      shows poor homology.

PMID- 7590362
TI  - Cloning and sequencing of the murine farnesyltransferase alpha-encoding cDNA from
      a cell line which expresses the human papillomavirus type-16 E6 gene.
AB  - Using a differential hybridization technique, the murine farnesyltransferase
      alpha (FTA)-encoding cDNA was cloned from a mouse 10T1/2 cell line which
      expresses the human papillomavirus type 16 (HPV16) E6 gene. Sequence analysis
      revealed that the murine 1647-bp FTA cDNA encoded 377 amino acid (aa). The murine
      and human sequences showed 83.2% nucleotide and 92.6% aa sequence identity.

PMID- 7590364
TI  - Cloning and sequencing of the cDNA encoding human P5.
AB  - The cDNA encoding human P5 was cloned and sequenced. The predicted 440-amino-acid
      (aa) sequence of human P5 contains two thioredoxin-like domains, which are also
      found in members of the protein disulfide isomerase superfamily. The human and
      hamster P5 genes reveal 87 and 93% similarity in their nucleotide and deduced aa
      sequences, respectively.

PMID- 7590363
TI  - Sequence and unusual 3' flanking region of the rat tRNA[Ser]Sec gene.
AB  - The single rat selenocysteine tRNA (tRNA[Ser]Sec) locus, including flanking
      sequence, was isolated by molecular cloning and its nucleotide (nt) sequence
      determined. In addition to the identification of likely regulatory elements 5' of
      this gene, this analysis also revealed a novel 3' repeat element consisting of
      three and a half repetitions of a 34-nt unit.

PMID- 7590365
TI  - Syncope: diagnosis of cardiac and noncardiac causes.
AB  - Syncope is a sudden and temporary loss of consciousness not caused by trauma or
      seizures. Patients age 65 and older are at elevated risk of syncope-related falls
      and sudden cardiac death. Cardiovascular causes are generally electrical (ie,
      arrhythmias) or mechanical (obstruction of central circulation at a cardiac valve
      or major vascular structure). Noncardiovascular causes include orthostatic
      hypotension, vasovagal reaction, micturition, carotid sinus hypersensitivity, and
      neurologic (eg, TIAs). Many causes of syncope can be diagnosed from a thorough
      history and physical exam. More extensive testing--ECG, Holter monitoring,
      electrophysiology study--may be indicated for selected patients with unexplained
      syncope and an unremarkable evaluation.

PMID- 7590366
TI  - Hypertension: special concerns in managing the older patient.
AB  - In most populations, average diastolic BP increases with age until the sixth
      decade and then remains constant, whereas average systolic BP continues to rise.
      Many studies have shown an increase in cardiac and stroke risk with increasing
      BP, even in elderly populations. Antihypertensive therapy in the elderly has been
      shown to reduce the risk of nonfatal and fatal stroke, nonfatal and fatal
      coronary heart disease, and all-cause mortality. The right combination of diet
      and lifestyle changes can help to control hypertension and reduce cardiovascular
      risk. For optimal results, give the patient as much informed choice as possible
      in the selection of therapies and setting of goals. Proceed cautiously when it is
      necessary to add pharmacologic therapy, whatever agent is chosen.

PMID- 7590367
TI  - Crops of 'pimples': has her acne returned at age 64?

PMID- 7590368
TI  - The secret war: don't miss post-traumatic stress disorder in World War II vets.

PMID- 7590370
TI  - [Problems in improvement of work conditions in railroad transport].
AB  - Within a short period of time the temperature conditions have been improved at
      working places of locomotive drivers and their assistants, a new switchboard for
      locomotives developed, noise and vibration in cabins were reduced, etc. Hygienic
      problems associated with improvement of locomotives are supervised by the
      Ministry of Communications and by special commissions.

PMID- 7590371
TI  - [Current problems of occupational morbidity of railroad workers].
AB  - Seven percent of all railway workers in Russia are occupationally exposed to
      adverse factors. A scientific validation of occupational diseases register is
      needed to be made, in order to improve disease control and prevention. Numerous
      measures aimed at improvement of the situation with health protection of railway
      workers are proposed.

PMID- 7590369
TI  - [Biomedical criteria referring to the category of especially hazardous chemicals
      transported by railroad].
AB  - Presents the list of especially dangerous freight and criteria for the
      determination of the most dangerous substances. Offers an extra list of agents
      characterized by expressed toxicity.